Jonathan Collin, M.D.
Alan Gaby, M.D.
Daniel Kanofsky, M.D., M.P.H.
Jack Taylor, D.C.
Roberta Baer, Ph.D.
Claire Cassidy, Ph.D.
Lilian Cheung, Sc.D.
L. John Hoffer, M.D., C.M., Ph.D.
J. Daniel Kanofsky, M.D., M.P.H.
Lawrence H. Kushi, Sc.D.
Mildred Seelig, M.D., M.P.H.
James P. Swyers, M.A.
Walter Willett, M.D., Dr.P.H.
Diet and nutrition research goes on in almost
every medical school, university, and pharmaceutical laboratory
throughout the world. Thus, the knowledge of how to prevent
illness and maintain health through nutrition grows every year.
However, for such areas as reversing the effects of chronic
disease through dietary or nutritional intervention or
determining levels of nutrients required to achieve optimal
metabolic or immune system functioning, there often is no
critical mass of researchers or funds to follow up promising
initial experimental results.
In fact, the history of nutrition research is
marked by examples where, for one reason or another, preliminary
reports of a positive therapeutic effect of a certain vitamin,
mineral, or nutritional manipulation appear but are often not
followed up by the overwhelming majority of the medical
community. In cases where such therapies eventually are proven to
be safe and effective, it is sometimes not until years or even
decades after the initial reports. The result is that many
individuals may die or suffer needlessly, while effective
interventions are available but not yet validated.
For example, in the 1930s, Australian
psychiatrist John Cade began a series of crude experiments on
guinea pigs in which he injected them with the urine of
psychiatric patients to test his hypothesis that mania--a mood
disorder characterized by, among other things, periods of
euphoria--might represent a state of intoxication resulting from
an excess of some commonly occurring metabolite. Depression, on
the other hand, might represent the effects of abnormally low
levels of the same metabolite (Johnson, 1984). Although all the
urine samples proved toxic to the guinea pigs--Cade traced the
toxicity to the urea component of the urine--the urine from the
manic patients was far more toxic than urine from the
schizophrenic or depressive patients.
In his attempts to find out what was increasing
the toxicity of the urea in the manic patients' urine, Cade
happened upon the compound lithium citrate, which he eventually
began injecting by itself into the guinea pigs to judge its
effect. To his amazement, the guinea pigs became lethargic and
unresponsive for several hours after receiving lithium, before
fully recovering. In 1949, Cade published the results of a crude
clinical trial, stating that lithium salts given to 10 manic
patients resulted in a dramatic improvement in each one's
condition (Cade, 1949). Unfortunately for Cade, just as his
results were reaching the United States, a number of table salt
substitutes containing lithium chloride had just been recalled by
the Food and Drug Administration (FDA) due to toxic side effects
and, in some cases, death with heavy use. So much publicity was
given to the toxicity associated with these salt
substitutes--which were marketed for use by people on
salt-restricted diets--that for 5 years after Cade's original
report, relatively little work with lithium was undertaken
(Georgotas and Gershon, 1981).
According to medical historian Frederick
Johnson (1984), "Cade's report of lithium treatment of mania
might well have succumbed to the same fate as that suffered by
many proposed therapeutic techniques before and after that time
... had lithium salts been at all expensive or hard to come
by...." Instead, because canisters of lithium salts were to
be found in most hospitals and pharmacies at the time, many
psychiatrists in the mid-1950s, for lack of adequate treatments
for manic disorders, simply started experimenting with lithium on
their own. By the mid-1960s, a spate of reports appeared in the
medical literature reporting on the effectiveness of lithium in
the treatment of manic and other psychiatric disorders (Gershon
and Yuwiler, 1960; Schlagenhauf et al., 1966). Today lithium, in
some patients with bipolar disorders (i.e., mood swings), is the
most successful therapeutic drug of the five major types of drugs
currently used in psychiatry (Horrobin, 1990), often producing
normalization in acute mania patients in 1 to 3 weeks.
A situation analogous to the lithium story
occurred in the late 1980s in the United States. Just as reports
were emerging that suggested the effectiveness of the amino acid
L-tryptophan in treating mild depression (Boman, 1988), chronic
insomnia (Demisch et al., 1987), and mood disorders (Maurizi,
1988), there was a severe outbreak of a sometimes deadly
inflammatory disorder called eosinophilia myalgia syndrome (EMS).
The cause of the EMS outbreak was linked by epidemiologists to
the over-the-counter use of tryptophan (Varga et al., 1993).
Although all cases of this disorder were eventually found to be
caused by contaminants in batches of tryptophan produced by a
single manufacturer in Japan (Barnhart et al., 1990) and not by
the effects of tryptophan itself, this nutritional supplement was
taken off the market by the FDA and is no longer available over
the counter. Just as with lithium, the publicity about toxicities
associated with tryptophan may have hindered rational scientific
discourse about the effectiveness of this nutritional therapy for
some time to come. In fact, FDA uses the tryptophan example to
justify its efforts to regulate as drugs most dietary and
nutritional supplements whose manufacturers make any health
claims (U.S. Food and Drug Administration, 1992).
There have been numerous other instances in
recent decades when individuals or groups of individuals have
advocated nutritional interventions or alternative dietary
lifestyles as a means of preventing or even treating disease and
have met not only indifference but often hostility. This was
especially true for those advocating vegetarianism or an
extremely low-fat diet as a means of preventing or treating
illnesses such as heart disease (see below). As was the case with
John Cade and lithium, it took many decades for the facts to win
out over misconceptions and biases.
The rest of this chapter discusses a number of
areas of diet and nutrition research in which there is at least
preliminary scientific evidence indicating the need for more
in-depth studies, but for which there often is no critical mass
of researchers or funds to follow up promising initial
experimental results. However, it should be noted that only an
overview of the field is presented, and it is by no means
comprehensive. This field of research is so complex and diverse
that no more than a few examples can be offered for each
First, however, it is instructive to discuss
briefly the evolution of the modern affluent diet and evidence
relating chronic disease with its excesses and micronutrient
deficiencies. Also presented is a discussion of the evolution of
present dietary guidelines and why some consider them inadequate.
Over the course of evolution, human beings (and
their primate predecessors) adapted gradually to a wide range of
naturally occurring foods, but the types of food and mix of
nutrients (in terms of carbohydrates, fats, and proteins)
remained relatively constant. Food supplies were often
precarious, and the threat of death from starvation was a
constant preoccupation for most of the Earth's inhabitants.
About 12,000 years ago, an agricultural
revolution brought profound dietary changes to many human
populations. The ability to produce and store foods became
widespread, and some foods, such as grains, were preferentially
cultivated. These new techniques and the overabundance of some
foods they produced presented novel challenges to the human
The Industrial Revolution, which began about
200 years ago in Europe and soon spread to North America,
introduced more radical changes in the human diet due to advances
in food production, processing, storage, and distribution. Recent
technological innovations, along with increased material
well-being, or affluence, and lifestyles that have allowed people
more freedom in deciding what and when they wish to eat
(amplified by modern marketing techniques), have led to even
further major dietary changes in developed countries. Indeed,
such innovations as sugared breakfast cereals and a variety of
snack items were unheard of before World War II; Hampe and
Wittenberg (1964) estimated that 60 percent of the items on
supermarket shelves in 1960 came into existence in the 15 years
following World War II.
Because changes in the dietary patterns of the
more technologically developed countries, such as the United
States, have been so dramatic and rapid, the people consuming
these affluent diets have had little time to adapt biologically
to the types and quantities of food available to them today. The
longer term adverse health effects of the affluent diets
prevailing in these countries--characterized by an excess of
energy-dense foods rich in animal fat, partially hydrogenated
vegetable oils, and refined carbohydrates but lacking in whole
grains, fruits, and vegetables--have become apparent only in
Comparisons of population groups have
demonstrated a close and consistent relationship between the
adoption of this affluent diet and the emergence of a range of
chronic, noninfectious diseases, such as coronary heart disease,
cerebrovascular disease, various cancers, diabetes mellitus,
gallstones, dental caries (cavities), gastrointestinal disorders,
and various bone and joint diseases (World Health Organization,
1990). Some nutrition and health experts believe that the
relationship between rapid changes in a population's diet and
rapidly changing disease and mortality profiles is reflected in
many recently acculturated (i.e., adapted to the dominant
culture) groups in the United States who are now eating a diet
more akin to that of the northern European and U.S. general
populations (see the sidebar on page 214).
For example, increasing rates of diabetes
mellitus have been reported in Native American and other
populations that suddenly switch from a traditional to a more
modern lifestyle (West, 1974). This disease has only recently
become a major health problem for Native Americans, who now often
have rates much higher than those found in either U.S. Caucasian
or African-American populations. Indeed, although the overall
rate of diabetes in the general U.S. population is between 1 and
3 percent, and 5 to 6 percent for those over age 35, it ranges
from 10 to 50 percent among Pima Indians 35 years of age and
older (Bennett et al., 1979; Neel, 1976). Furthermore, in Hawaii,
the incidence of breast cancer for Caucasians is similar to U.S.
mainland rates, but the incidence among Hawaii's Japanese
population is more than twice the rate in Japan and approaches
the rate for Caucasians (Muir et al., 1987).
The reasons for these abnormally high disease
rates in American Indian and other non-Caucasian populations are
complex; however, they include obesity related to changes in
activity patterns and, probably, the increased consumption of
refined carbohydrates and sugar. Also, intake of dietary fiber
has decreased dramatically. Excessive caloric consumption in some
of these populations also may be a major contributor; one study
found that obese American Indians consumed 250 to 1,600 more
calories than were recommended for persons of their height,
gender, age, and level of activity (Joos, 1984).
In one of the few studies of its kind, a group
of Native Hawaiians with multiple risk factors for cardiovascular
disease believed to be related to consuming a nontraditional diet
were placed on a "pre-Western contact," or traditional,
Hawaiian diet to assess its effect on obesity and cardiovascular
risk factors. Twenty individuals were placed on a diet low in fat
(7 percent), high in complex carbohydrates (78 percent), and
moderate in protein (15 percent) for 21 days. The subjects were
encouraged to eat as much as they wanted. At the end of the diet
modification period, the average weight loss was 7.8 kilograms
(approximately 17 lbs.), and the average serum cholesterol
dropped by about 14 percent. Blood pressure decreased an average
of 11.5 mm Hg systolic and 8.9 mm Hg diastolic (Shintani et al.,
Due to the rapid rise in chronic illness
related to diet in recent decades, the focus of nutrition
research has shifted from eliminating nutritional deficiency
resulting from undernutrition to dealing with chronic diseases
caused by nutritional excess, or "overnutrition." Since
the 1950s, researchers have identified a number of types of
dietary excess that appear to influence the incidence and course
of specific chronic diseases.
Another growing concern among nutrition
researchers is the accumulation of evidence indicating that
inadequate intakes of some micronutrients over a long time may
increase the risk of developing a variety of disease conditions,
including coronary heart disease, many cancers, cataracts, and
birth defects. Earlier, many of these conditions were not even
considered diet-related. Furthermore, many other components of
foods, in addition to those traditionally considered nutrients,
may be important in achieving optimal health. Unfortunately, the
"standard" American diet, while rich in calories,
contains processed foods deficient in many important
micronutrients and other components of the original unrefined
The Federal Government has been involved in
developing nutrition guidelines for the American public since the
mid-1800s, when the U.S. Department of Agriculture (USDA) was
established. However, such guidelines traditionally had dealt
with how to prevent nutritional deficiencies, as well as how to
promote the consumption of U.S. agricultural products. Only in
the past several decades, as the focus of public health policy
has shifted from preventing disease caused by nutritional
deficiencies to preventing disease caused by overnutrition or
nutritional imbalances, have Federal dietary guidelines attempted
to address the latter. Today, such guidelines are becoming more
difficult to develop and often meet fierce resistance from
various lobbying groups when they are disseminated (Nestle,
Nevertheless, since the early 1970s, USDA and
other Federal agencies and advisory groups have periodically
released diet and nutrition guidelines dealing with preventing
chronic illness related to nutrition. This material typically
targets public health policymakers, medical doctors, or the
general public. Two of the better known current Federal dietary
and nutritional guidelines, from which public health policy is
made, are the recommended daily allowances (RDAs) and the Food
RDAs are defined as the average daily amounts
of essential nutrients estimated, on the basis of available
scientific knowledge, as adequate to meet the physiological needs
of practically all healthy persons (Monsen, 1990). (See figure
1.) To establish the standards for RDAs, which are updated
periodically (most recently with the 10th edition in 1989; see
Monsen, 1990), the Food and Nutrition Board of the National
Academy of Sciences critically evaluates the literature on human
requirements for each nutrient, examines the individual
variability of requirements, and tries to estimate the efficiency
with which the nutrients are biologically available and used from
foods consumed. The RDAs are levels that should be reached as
averages in a period of several days, not necessarily daily.
RDAs are not meant to be guidelines for
consumers; they were initially designed to serve as standards for
planning food supplies for population groups (National Research
Council, 1989). However, they are used as a partial basis for the
development of other guidelines that are intended for consumers,
such as the Food Guide Pyramid, which was released by USDA in
1992 to replace the old "basic four" food groups. The
Food Guide Pyramid is designed to give consumers information on
how to eat a "balanced" diet that will provide them
with the RDAs for essential nutrients while lowering their risks
of chronic illness due to nutritional excesses (Journal of the
American Dietetic Association, 1992). Sweets, fats, and oily
foods are at the top of the pyramid, indicating that they should
be consumed in small amounts. Dairy products such as milk,
yogurt, and cheese, and meats, poultry, fish, dried beans, eggs,
and nuts are just below, indicating they should be consumed in
moderation. Fruits and vegetables follow; bread, cereal, rice,
and pasta are at the bottom of the pyramid, indicating that they
should be consumed in rather large amounts in comparison with the
foods at the top of the pyramid (see figure 2).
Guidelines such as the Food Guide Pyramid are
intended to inform consumers, as well as public health
policymakers, about what kinds and amounts of certain foods are
best suited for maintaining health and lowering the risks of
nutrition-related illnesses. Generally, this approach to
affecting health through diet and nutrition interventions
involves manipulating the "typical," or mainstream,
diet so that foods with less nutritional value are eaten less and
foods with more nutritional value are eaten more.
The Federal Government's approach to dietary
intervention, which has been formulated over the years by boards
composed of nutrition scientists, generally does not recommend
supplementing this "typical" diet with vitamins or
nutritional supplements (National Research Council, 1989). It
also does not take a "good food" or "bad
food" approach (Herron, 1991) or suggest that certain foods
are "off limits" because of their propensity to cause
chronic disease (Nestle, 1993).
However, this is only one approach to promoting
health and preventing illness through dietary intervention. There
are many "alternative" dietary approaches that contend
that no matter how much one manipulates the typical American
diet, it is not enough to promote optimal health or stave off
eventual chronic illness. Alternative approaches represent a
continuum of philosophies, from the idea that diet
supplementation somewhat beyond RDAs is necessary to promote
optimal health to the idea that supplementation well above RDAs
is often required to treat some chronic disorders. Further along
this continuum is the approach advocating drastic modification of
patients' diets--either completely eliminating or adding certain
types of foods--to treat specific types of conditions, such as
cancer and cardiovascular disease. Finally, there is the approach
that promotes eating a less refined, more
"naturalistic" diet as the only way to promote optimal
health and prevent illness. This last approach holds that staples
of the typical American diet (e.g., meat and dairy products) are
basically unhealthful and should be avoided altogether. The
remainder of this chapter describes representative alternative
therapies along this continuum.
Vitamins are organic substances required by all
living organisms for healthy life and growth. Among their many
properties, vitamins function as coenzymes (helpers to the
primary enzyme) in metabolic reactions. Higher animals,
particularly humans, cannot synthesize vitamins and therefore
must ingest them as part of their diet. Deficiency in a
particular vitamin results in a specific vitamin deficiency
disease, such as rickets (a bone deformity from lack of vitamin
D) and scurvy (the infamous sailors' deficiency disease of old,
caused by lack of vitamin C-containing fruits and vegetables on
sailing ships). Each type of deficiency disease is typically
characterized by a "classic" set of symptoms.
Vitamins of the B complex and vitamin C are
water soluble (i.e, they dissolve readily in water). The B
complex vitamins are found in food sources such as whole wheat
bread, fruits, green and yellow leafy plants, and animal sources
such as eggs, dairy products, and liver. They include B1
(thiamine), B2 (riboflavin), B3 (nicotinic acid, or niacin),
pantothenic acid, B6 (pyridoxine), biotin, folic acid, and B12.
Certain other substances, such as choline, also may be considered
as belonging to the B complex. Vitamin C (ascorbic acid) is
present in certain fruits and green vegetables.
All the remaining vitamins (A, D, E, and K) are
fat, or lipid, soluble (i.e., they dissolve more readily in oil
than in water). Vitamin A (in the form of carotenoids) occurs
naturally in green leafy and yellow vegetables; spinach,
collards, kale, chard, carrots, and sweet potatoes are
particularly good sources. Vitamin E (tocopherol) is found in
many plant oils, such as corn oil. In adults vitamin K is
supplied by intestinal bacteria.
A number of other minerals and nutrients, such
as iron, calcium, magnesium, selenium, and zinc, have been found
essential for preventing deficiency diseases. For example,
magnesium, which is required for the activation of more than 300
enzymes in the body and for the use of some vitamins and
minerals, is required for normal function and structure of the
arteries, heart, kidneys, and bone (Seelig, 1980), and for the
neuromuscular system (Durlach, 1988; Galland, 1991). There also
are a number of "essential" amino acids and fats (that
is, humans cannot synthesize them). Some other amino acids are
considered "semiessential" because humans cannot
synthesize them fast enough to meet metabolic needs.
Research base. The relatively few studies that
have explicitly investigated the role of vitamin and mineral
supplements in promoting health and preventing disease have
generally found benefits from the supplements. In fact, evidence
is increasing rapidly for a beneficial role of supplementation
with a number of nutrients, including vitamins B6, C, and E;
beta-carotene and other carotenes; folic acid; calcium;
magnesium; and other factors. Although there is little dispute
about the importance and functions of many vitamins and
nutrients, questions arise regarding the levels necessary to
produce optimum health. Many contend that the optimal levels of
these compounds can be obtained in a normal diet and that the
effect of additional amounts is negligible (National Research
Council, 1989). To answer such questions, it is first necessary
to compare some nutrient levels in the typical American diet with
current RDAs as well as with what some now consider to be optimal
levels based on the most recent research. The following includes
data from recent studies on the minerals calcium, iron, and
magnesium as well as the vitamins C, D, E, beta-carotene, and
Calcium. Some authorities have recommended that
women (including young women) consume 1,000 to 1,500 milligrams
(mg) of calcium per day to develop and maintain bone health and
prevent osteoporosis (Office of Medical Applications of Research,
1984). Although it is technically feasible to achieve this level
by diet alone, most people in the United States do not get that
much calcium in their diet. In fact, the median intake among
American women is only 600 mg per day, or around half the optimal
level. Furthermore, 25 percent of women consume less than 400 mg
per day (based on an average of 4 nonconsecutive days over 1
year) (U.S. Department of Agriculture, 1988).
Iron. Approximately 8 percent of low-income
women and 10 to 20 percent of low-income children are believed to
be iron deficient (Public Health Service, 1989). While the RDA
for women is 15 mg per day, only slightly more than 10 percent of
women achieve this goal from diet alone; less than 10 percent of
low-income women achieve this level (Block and Abrams, 1993; U.S.
Department of Agriculture, 1988). Iron deficiency is not an
important public health problem among men; indeed, some evidence
suggests that iron overload in men may be a source of illness,
such as heart disease (Sullivan, 1992). Absorption of iron from
supplements and plant sources is quite low if body stores of iron
are adequate; however, iron from red meat continues to be
absorbed even if body stores of iron are plentiful (Ascherio and
Willett, 1994). Therefore, until this hypothesis can be more
fully studied, it may be prudent for men to avoid daily
consumption of red meat.
Magnesium. Extensive metabolic balance studies
done by the USDA Research Service showed that the ratio of
dietary calcium to magnesium that best maintained equilibrium
(i.e., output equaling intake) was 2:1 (Hathaway, 1962). This
ratio is achieved at the median magnesium intake of approximately
600 mg per day. However, dietary surveys taken in the last decade
have found that most Americans' diets provide less than 300
mg/day (Lakshmanan et al., 1984; Morgan and Stampley, 1988;
Spillman, 1987). Thus, like that of calcium, the median daily
intake of magnesium in the United States appears to be
Long-term magnesium deficiency causes damage to
arteries and the heart in all species of animals tested--rodents,
cats, dogs, cattle, and monkeys (Seelig, 1980; Seelig and
Heggtveit, 1974). It also adversely affects fat metabolism,
increasing the "bad" lipids--low-density lipoprotein
(LDL) cholesterol and triglycerides, which are associated with
atheromas (fat deposits in arteries)--and decreasing the levels
of "good" lipids--high-density lipoprotein (HDL)
cholesterol, which remove fat deposits from the arterial wall
(Altura et al., 1990; Rayssiguier, 1981, 1984, 1986; Rayssiguier
et al., 1993).
On the other hand, magnesium supplementation
appears to be effective in reversing this process. For example in
a double-blind, placebo-controlled study, 47 patients with
coronary artery disease and heart attacks were treated with oral
magnesium or placebo for 3 months. Those who received the
magnesium experienced a 27-percent decrease in the
"bad" lipids in contrast to a slight increase in the
placebo group. There was also a tendency toward increased HDL in
the magnesium group (Rasmussen et al., 1989a). The investigators
observed that these findings support the assumption that
magnesium deficiency might be involved in the causation of
coronary artery disease. Oral magnesium preparations have also
favorably influenced blood lipids in diabetes mellitus, lowering
high levels of LDL and raising low levels of HDL (Corica et al.,
In another study in which about half of 374 men
at high risk for serious cardiovascular disease were put on a
diet high in magnesium (a predominantly vegetarian diet
containing 900 to more than 1,200 mg of magnesium daily) and half
were put on a regular diet (containing about 300 to 500 mg of
magnesium daily), sudden cardiac deaths were 1.5 times more
common in the low-magnesium group. Total complications occurred
in 60 percent of the low-magnesium group versus 28.6 percent of
the high-magnesium group (Singh, 1990). Total mortality was 18
percent and 10.7 percent in the low-and high-magnesium groups,
respectively. Furthermore, in a 6-week study of 206
non-insulin-dependent diabetic patients there was significant
lowering of LDL levels and slight raising of HDL levels on a
high-magnesium diet versus no change in 194 comparable patients
on their usual diets (Singh et al., 1991).
Epidemiological evidence also supports the
premise that magnesium protects against cardiovascular disease in
humans. Areas of the world where the intake of magnesium is high
from either drinking water or diet have low prevalence of
cardiovascular disease (Anderson et al., 1980; Durlach et al.,
1989; Eisenberg, 1992; Hopps, 1981; Leary, 1986; Marier, 1978).
In the United States, the Southeast (where water is soft and is
low in magnesium) is known as the heart attack-kidney stone belt,
whereas the northern Midwest Plains states (where water is hard
and is high in magnesium) have lower cardiovascular disease rates
and longer life expectancies (Hopps, 1981; Hopps and Feder,
In Germany, large-scale retrospective studies
of nearly 5,000 patients indicate that magnesium supplements
added to drugs used to prevent preterm delivery resulted in
improved weights of infants, reducing incidence of low birth
weights (whether due to prematurity or intrauterine growth
retardation), and decreased the incidence of toxemias of
pregnancy, including pregnancy-induced hypertension,
preeclampsia, and eclampsia (Conradt, 1984; Conradt and
Weidinger, 1982; Conradt et al., 1984). Two randomized
double-blind studies of a total of 1,500 pregnant women, half of
whom received placebo and the other half a magnesium salt
supplement, showed that significantly fewer of the magnesium
group developed eclampsia; in addition, there were significantly
fewer low birth weights among the infants of the magnesium group.
The conclusion was that magnesium supplements during pregnancy
improved the outcome (Kovacs et al., 1988; Spaetling and
Spaetling, 1987). It has been suggested that magnesium deficiency
is a contributory factor in these conditions (Conradt et al.,
1984; Kontopoulos et al., 1980; Seelig, 1980; Weaver, 1988), a
concept that has been proved in magnesium deficiency-induced
hypertension of pregnancy and in low birth weight of lambs born
to ewes fed low-magnesium diets (Weaver, 1986, 1988). That
preeclamptic women retain more magnesium after a loading test
(injection of magnesium salt solution) than normal women do is
direct evidence of the magnesium deficit in toxemia of pregnancy
(Kontopoulos et al., 1980; Valenzuela and Munson, 1987).
Vitamin C. Vitamin C is an important
antioxidant nutrient that is synthesized by most animal species
but not by humans. The current RDA is 60 mg, an amount easily
obtainable in diet. Nevertheless, 25 percent of women consume
less than 40 mg per day in their 4-day average (U.S. Department
of Agriculture, 1988). The optimal level of vitamin C intake is
unknown, but a diet rich in fruits and vegetables can provide 250
to 500 mg per day (Becker, 1993). Interestingly, estimates of
nutrition during the Paleolithic Age (the Old Stone Age, roughly
1,000,000 to 9,000 B.C.) suggest that early humans may have
consumed as much as 390 mg per day of vitamin C (Eaton and
Konner, 1985). As with vitamin E (see below), there is evidence
that intakes well above 60 mg per day may reduce the risks of
cataracts. The potential therapeutic attributes of vitamin C are
discussed in detail in the next section, Orthomolecular Medicine.
Vitamin D. The current RDA for adults is 200
international units (IUs). However, there are few studies in
adults to verify that this is the optimal level (Gloth et al.,
1991). Although this vitamin can be synthesized by humans by
exposure to the sun, many elderly persons, for example, who are
often inside much of the day get little or no sun. Since
fortified milk is the principal dietary source of vitamin D,
persons who obtain little calcium from milk or who have
inadequate sun exposure may have inadequate vitamin D intake
(Gloth et al., 1991).
Vitamin E. Vitamin E, or alpha-tocopherol, is
another important antioxidant nutrient. The current RDA for
vitamin E is 8 IU for women and 10 for men. This is a reduction
from an earlier RDA of 30 IU for both men and women. A
well-selected diet containing numerous servings of fruits and
vegetables, nuts, whole-grain breads, and vegetable oils can
achieve a diet containing 30 IU (Becker, 1993). However, few
Americans consume such a diet.
Current median intake in the U.S. population is
approximately 5 IU, with 10 percent of the population consuming
little more than 3 IU. Levels of 100 IU or higher have been
associated with significantly reduced risk of coronary heart
disease in both men and women (Rimm et al., 1993; Stampfer et
al., 1993). However, this effect has been seen at levels
obtainable only from supplements. Indeed, the use of vitamin E
supplements for 2 or more years was associated with a 41-percent
decrease in risk of coronary disease among women (Stampfer et
al., 1992) and a 37-percent decrease in men (Rimm et al., 1993).
In addition, consumption of supplements containing vitamin E has
been associated with significant reduction in risk of oral cancer
(Gridley et al., 1992). This effect was seen even after
controlling for factors such as smoking and alcohol consumption.
Moreover, although persons with a high intake of fruits and
vegetables had a 40-percent reduction in risk of oral cancer,
those who used a vitamin E supplement in addition to high fruit
and vegetable intake had an 80-percent reduction in risk.
Cataracts are a major cause of blindness
worldwide and represent a significant fraction of health care
costs in the United States. A number of studies have found that
ingesting antioxidants, such as vitamin E, significantly reduced
the risk of cataracts (Taylor, 1992). In one study, daily
supplementation with 400 IU of vitamin E was associated with a
60-percent reduction in risk of cataracts, whereas daily use of
300 mg or more of vitamin C resulted in a 75-percent reduction in
cataract risk (Robertson et al., 1989). Others have also found a
high intake of dietary carotenoids associated with reduced
cataract risk (Hankinson et al., 1992; Jacques et al., 1988).
Beta-carotene. This antioxidant is found in
orange fruits and vegetables such as carrots, sweet potatoes, and
squash, and in dark green leafy vegetables. As much as 20 to 30
mg can be obtained from just a few fresh carrots. This also is
the level currently being used as the test dose in a number of
intervention studies to determine whether it can reduce cancer
risk (see below). However, current median intake is less than 2
mg per day, and approximately 25 percent of Americans consume 1
mg per day or less (U.S. Department of Agriculture, 1988). There
also is evidence that other naturally occurring carotenoids, in
addition to beta-carotene, may be important as antioxidants in
reducing the risk of disease.
A number of recent studies have suggested that
beta-carotene, among other antioxidants, may have a protective
effect against certain cancers. For example, low blood levels of
beta-carotene are consistently associated with the subsequent
development of lung cancer (Ziegler, 1991).
Furthermore, in a recent prospective trial in
China funded by the National Cancer Institute (NCI) and the
Cancer Institute of the Chinese Academy of Medical Sciences,
29,584 adults were given several combinations of vitamin and
mineral supplements. Linxian, a rural county in Henan province,
northern China, has one of the highest rates of esophageal cancer
in the world. Death rates for this cancer in Linxian are 10 times
higher than the Chinese average and 100 times greater than for
During the period of the study, there were
2,127 deaths among study participants, with 32 percent of all
deaths resulting from esophageal or stomach cancer. Only the
combination of beta-carotene, vitamin E, and selenium
significantly reduced death rates in the study population, and
most of the reduction was due to lower cancer rates. This
included not only a reduction in esophageal cancer and stomach
cancer but also a 45-percent reduction in fatal lung cancer that
did not reach statistical significance (Blot et al., 1994). The
doses in the study were typically two to three times the U.S.
RDA, and the risk reduction appeared to begin 1 to 2 years after
vitamin and mineral supplementation began.
However, two other recent trials to assess the
ability of beta-carotene to prevent cancer have not shown such
positive results. A Finnish study in which almost 30,000 male
smokers aged 50 to 59 were given daily supplements of vitamin E
(alpha-tocopherol), beta-carotene, or both found no reduction in
the incidence of lung cancer (Heinonen and Albanes, 1994). In
fact, the study observed a higher incidence of lung cancer among
men who received the beta-carotene than among those who did not.
Nor was there any reduction in the formation of colon polyps--a
precursor of colon cancer--in a study in which 864 individuals
received placebo or beta-carotene (25 mg daily), vitamin C (1 g
daily), and vitamin E (400 mg daily) for 4 years (Greenberg et
There are several problems with trying to
compare these studies. Most important is whether a period of 4 to
6 years is sufficient to detect a beneficial effect of an agent
that acts early in the development of cancer--which could be
decades before the cancer is diagnosed. Also, it is possible that
only persons with low levels of beta-carotene may benefit from
supplementation. The New England Journal of Medicine managing
editors warned in a recent editorial that consumers should not
overinterpret the latest negative findings, just as they should
not overinterpret the earlier positive findings (Angell and
Folic acid (folate). The current RDA for folate
is 180 micrograms (mg) per day for women, but recent studies have
shown that intake of 400 mg by pregnant women can greatly reduce
the risk of neural tube defects (i.e., defects of the spinal cord
tube) (Willett, 1992). Intake must be at this level in the
earliest weeks after conception to be effective. Unfortunately,
most women are not yet aware that they are pregnant then.
Researchers examining the role of folate in
preventing cancer and cardiovascular disease have found that less
than optional levels of folate may be linked to these diseases.
For example, a recent study of almost 1,500 male physicians
revealed that the risk of suffering a heart attack was elevated
more than threefold by a common metabolic abnormality called
homocysteinemia, which is correctable by consuming more folate.
None of the study participants who suffered heart attacks would
be considered folate deficient by current nutritional standards.
However, the results of this study indicate that their intake of
folate was clearly less than optimal for preventing
cardiovascular disease (Stampfer et al., 1992). In addition,
folic acid supplementation was associated with reduced risk of
colorectal cancer (Giovannucci et al., 1993). In contrast, folate
from food alone was not significantly related to reduced risk of
In another double-blind, placebo-controlled
trial of 96 healthy persons over age 65, the consumption of
vitamin and mineral supplements was associated with a significant
reduction in illness from infections and improved immune function
(Chandra, 1992). The vitamin used was a therapeutic-level,
multiple vitamin containing, among other nutrients, 400 mg of
folate and 16 mg of beta-carotene. Participants receiving the
vitamin formulation experienced half as many days of
infection-related illness over the treatment year as did persons
receiving the placebo (i.e., 23 days for the treatment group
compared with 48 days for the untreated group).
Thus, it may be that approximately 400 mg per
day of folic acid is necessary for men and women of all ages.
Although this level can be obtained from a well-chosen diet
containing, for example, six servings of fruit or vegetables and
fortified cereal per day (Block and Abrams, 1993), few in the
United States consume such a diet. In fact, a recent study found
that 25 percent of pregnant women who were surveyed consumed only
128 mg or less of folate and 10 percent consumed only 90 mg per
day in their 4-day average (Johnson et al., 1994).
Risks associated with vitamin and mineral
supplementation. All vitamins, as well as other substances,
including water, can be toxic at some upper level. Under certain
conditions or for particular subgroups, dangers may arise in
taking large doses of some vitamins and minerals. For example,
persons on anticoagulant (blood-thinning) therapy should avoid
high doses of vitamin E, because prolonged bleeding can occur.
Accidental poisonings of children have occurred with a number of
vitamins, most notably with large doses of iron and vitamins A
and D. Indeed, the accidental fatal poisoning of children by
ingestion of their mothers' high-dose iron tablets is a health
problem that deserves wider recognition. Childproof caps have
been required on iron tablets for several years, but greater
awareness among parents is needed to prevent children from
removing such protective devices.
Nevertheless, evidence suggests that most
vitamins are safe for long-term use at levels well above the RDAs
for most adults. For example, Hathcock (1991) found a
"possible adverse effect level" for vitamins C, E, B6,
and folate only with long-term ingestion at 10 times the RDA or
greater and at 5 times the RDA for vitamin A. Minerals such as
iron, zinc, and selenium, however, may be associated with greater
risk of toxicity at levels of less than 10 times the RDA for
The use of pharmacological doses (i.e., levels
of intake substantially above those traditionally assumed
necessary to prevent deficiency) of some vitamins and magnesium
salts is an accepted practice in mainstream medicine for
treatment of a few established conditions. However, such cases
are relatively isolated, and the use of pharmacological doses of
vitamins for many diseases remains controversial. This subject is
Varying the concentrations of substances
normally present in the body may control mental disease.
In theory, the concept behind orthomolecular
medicine is quite simple. Orthomolecular medicine is the pursuit
of good health and the treatment of disease with the optimal
concentration of substances normally present in the body. Nobel
laureate Linus Pauling first used the term orthomolecular in his
1968 article, "Orthomolecular Psychiatry," in the
journal Science (Pauling, 1968). The prefix ortho implies correct
or proper; in using the term orthomolecular, Pauling was calling
for the "right molecules in the right amounts" (Huemer,
Pauling's Science article concentrated on the
psychiatric implications of the concept. It referred to the work
of two Canadian psychiatrists, Abram Hoffer and Humphrey Osmond,
who had for several years been treating acute schizophrenia with
large doses of nicotinic acid (vitamin B3) and vitamin C as
enhancements to or replacements for the then state-of-the-art
therapies, electroconvulsive therapy (ECT) and major tranquilizer
therapy. Hoffer and Osmond first became interested in vitamin B3
as a therapeutic biochemical agent because of reports in the
literature that patients with pellagra, a disease caused by a
vitamin B3 deficiency, displayed many of the same psychiatric
symptoms as did patients with schizophrenia.
In a series of double-blind, placebo-controlled
clinical trials in the 1950s and early 1960s, Hoffer and Osmond
began giving patients with schizophrenia up to 6 grams a day of
vitamin B3, as well as large doses of vitamin C and other
vitamins, in addition to the normal treatment regimen. They
reportedly doubled the recovery rate, halved the
rehospitalization rate, and practically eliminated the suicide
rate among this patient group in comparison with the patients
receiving only ECT or tranquilizers. These positive results were
reported in 5-, 10-, and 15-year followups (Hoffer and Osmond,
1960, 1964; Osmond, 1969).
In his Science article, Pauling indicated some
of the ways orthomolecular concepts could be usefully applied to
many other areas of medicine. He then suggested that increasing
the intake of such nutrients to levels well above those usually
associated with prevention of overt deficiency disease could have
previously unrecognized health benefits for some, but not all,
people (Pauling, 1968).
One outcome of the increased attention focused
on the megavitamin issue by Pauling's Science article was the
publication of a report by the American Psychiatric Association's
Task Force on Megavitamin Therapy in Psychiatry (Lipton et al.,
1973), which roundly criticized the work of Hoffer and Osmond and
declared megavitamin therapy to be of no value. Proponents of
this new form of medical intervention criticized these reports as
having numerous misstatements and inaccuracies. In particular,
orthomolecular psychiatry proponents argued that the two reports
had based their conclusions on flawed studies that attempted to
replicate the use of niacin for the treatment of schizophrenia in
chronically hospitalized psychotic patients. The treatment,
according to proponents, had been shown effective only in acute
schizophrenia of relatively recent onset (i.e., within a few
months to a year or two), which meant that trials in chronically
ill patients were doomed to failure (Hoffer, 1974; Pauling,
Concurrent with the studies of niacin in
psychiatry in the early 1970s, Pauling began collaborating with
Scottish surgeon Evan Cameron on a series of retrospective
studies to determine whether vitamin C was effective in the
treatment of cancer. In the late 1970s, Pauling and Cameron
reported a significant prolongation of lifespan of vitamin
C-treated patients over that of cancer patients who did not
receive vitamin C therapy (Cameron and Pauling, 1976). These
studies were undertaken as followups to a clinical trial
conducted by Cameron with Alan Campbell, which reported complete
cessation of tumor progression in 3 patients and complete tumor
regression in 5 patients of 50 advanced-cancer patients treated
intravenously for long periods with high doses of vitamin C
(Cameron and Campbell, 1974).
The results of Pauling and Cameron's
retrospective studies were published in the Proceedings of the
National Academy of Sciences (PNAS), which took the unusual step
of running an accompanying editorial along with the second PNAS
paper criticizing its methodology and calling for better designed
double-blind prospective studies to confirm or refute vitamin C's
anticancer activity. Following this, the NCI funded two highly
publicized clinical trials of vitamin C at the Mayo Clinic in
Rochester, MN, both of which reported negative results for the
use of vitamin C in the treatment of cancer (Creagan et al.,
1979; Moertel et al., 1985). However, Pauling argued that the
first Mayo Clinic study was flawed because almost all the
patients had previously received chemotherapy, which may have
affected their response to vitamin C. He contended that the
second study was flawed as well, in part, because it did not use
Cameron's protocol and vitamin C therapy was not carried out for
long enough (Richards, 1986).
Despite the negative results of the Mayo Clinic
studies, Pauling and others continued to promote vitamin C and
other immune-modulating substances as important adjuvants to the
treatment of cancer. They believed that neither surgery,
radiation, nor chemotherapy could ever be completely effective in
eliminating all the cancer cells from a patient's body. Thus it
is necessary, they argued, to enhance the patient's immune
defenses against cancer with large doses of vitamin C (Cameron
and Pauling, 1976). The rationale for this is based on earlier
observations that cancer patients tended to be significantly
depleted of vitamin C (Baird and Cameron, 1973; Bodansky et al.,
1951) and that those animals that have the ability to produce
their own vitamin C significantly increased their own production
of vitamin C--to an equivalent of 16 grams per day for the
average human--when challenged with a potent carcinogen or when
experimentally burdened with cancer (Burns et al., 1960; Schmidt
et al., 1963). However, Cameron and Pauling never suggested that
vitamin C (or other nutrients) should be used instead of
conventional cancer therapy but rather as an adjunct to therapy
(Cameron and Pauling, 1976). Pauling and others also have
advocated high doses of vitamin C as a means of treating or
preventing other diseases, including the common cold and
influenza (Pauling, 1976).
Although the negative results from the Mayo
Clinic studies as well as results from the American Psychiatric
Association study managed to put a damper on claims made by the
proponents of orthomolecular medicine for more than a decade,
interest in this subject has been renewed recently. One reason is
that in isolated instances, orthomolecular treatments have indeed
proved effective in treating certain chronic illnesses. For
example, megadose niacin is now routinely prescribed to treat
hypercholesterolemia (i.e., abnormally high levels of LDL
cholesterol in the blood) and has been shown to reduce cardiac
mortality in large-scale trials (Vega and Grundy, 1994; Zhao et
al., 1993). Likewise, vitamin A in dosages substantially higher
than the RDA is a highly effective treatment for an uncommon form
of leukemia (Bunce et al., 1994; Skrede et al., 1994), and the
effectiveness of high-dose vitamin E in surgical wound healing
and burn therapy has been recognized for years (Haberal et al.,
1987; Zhang et al., 1992).
Finally, as the data have mounted on the role
such antioxidants as vitamin C may play in preventing disease and
maintaining health, younger investigators are increasingly being
attracted to this field. These investigators are now equipped
with more accurate and sensitive methods for exploring the
validity of theories that were previously rejected outright but
were never adequately tested (Barinaga, 1991).
Research base. The following are examples of
orthomolecular treatments for which there is at least preliminary
evidence suggesting their effectiveness in treating various
chronic, debilitating illnesses but for which larger, more
detailed studies are needed. This is by no means a comprehensive
list. For the reader's convenience, these therapies are presented
by type of conditions for which they are applied. These
conditions include AIDS, cancer, a variety of heart and vascular
conditions, lymphedema, and mental and neurological disorders.
Acquired immunodeficiency syndrome (AIDS). AIDS
is a clinical disorder caused by a retrovirus infection (i.e,
human immunodeficiency virus, or HIV), which is the end stage of
a progressive sequence of immunosuppressive changes. The
drawbacks of current pharmacological therapy for HIV infection,
such as zidovudine (AZT), include deleterious toxic side effects,
inability to improve the immune dysfunctions and undernutrition
initiated by the retrovirus infection, and the occurrence of
AZT-resistant HIV strains. These drawbacks necessitate new
strategies for developing novel therapies to treat AIDS. Low
toxicity nutritional agents with immuno-enhancing and antioxidant
activities may help normalize retrovirus-induced immune
dysfunctions, undernutrition, and other pathological symptoms,
thereby retarding the progression of the disease to AIDS. Data on
the immune-stimulating effects of vitamin A and beta-carotene in
HIV-infected individuals are presented below.
Vitamin A. In the early 1980s, Seifter and
colleagues showed through a series of experiments that vitamin A
or beta-carotene (its precursor) decreases the immune deficiency
that results when animals are exposed to a wide variety of
immunocompromising conditions such as trauma, infection,
irradiation, and treatment with cytotoxic agents (Seifter et al.,
1982, 1983a, 1983b, 1984). Seifter and others also studied the
effects of vitamin A supplementation in animals infected with the
Moloney murine sarcoma virus, a retrovirus having many features
in common with human immunodeficiency virus (HIV), the virus that
causes AIDS (Kanofsky et al., 1987, 1990; Seifter et al., 1982,
1985, 1991). The vitamin A supplementation Seifter and his
colleagues used in those experiments was approximately 10 to 15
times the recommended dietary allowance.
There is evidence suggesting that vitamin A
supplementation in immune-compromised individuals may be
necessary to correct a vitamin A deficiency caused by HIV
infection. For example, Lack and colleagues (1993) found that
approximately 50 percent of 120 HIV-positive patients, who were
both symptomatic and asymptomatic, had a low serum vitamin A
level. In another study, Semba and colleagues (1993) measured
serum vitamin A levels in HIV-positive drug abusers and concluded
that vitamin A deficiency may be common during HIV infection. Low
vitamin A status was independently associated with decreased CD4
cells and a much greater mortality rate.
Beta-carotene. Alexander and colleagues (1985)
reported that extremely large oral doses of beta-carotene (180 mg
per day) can increase the number of CD4 cells in the blood of
healthy humans, with no observable toxicity. The CD4 cell is the
white blood cell that becomes markedly depressed in AIDS
patients. According to these researchers, "Our data suggest
that beta-carotene administration might be considered for
patients with AIDS."
Coodley and colleagues (1993), in an 8-week,
double-blind crossover study of 21 HIV-positive patients,
compared 180 mg per day of beta-carotene with placebo. The
results showed a statistically significant increase in total
white blood cell count, percent change in CD4 count, and percent
change in CD4:CD8 ratios. The CD4:CD8 ratio is often used as an
indicator of whether a patient's status is getting worse, holding
steady, or improving.
Watson and colleagues gave a much smaller dose
of beta-carotene (60 mg per day) to 11 HIV-infected patients over
4 months. The authors saw no change in T-helper lymphocytes
(CD4), T-suppressor lymphocytes (CD8), or total T-cell
lymphocytes. However, they did see an increase in the number of
cells with natural killer markers and markers of activation
(IL-2R, transferrin receptors) (Garewal et al., 1992). This
indicates that beta-carotene may be enhancing certain aspects of
the immune response.
Furthermore, Fryburg and colleagues (1992) gave
120 mg per day of beta-carotene and 1 multivitamin tablet a day
to seven AIDS patients for 4 weeks. The mean CD4 count at
baseline (i.e., before treatment) was approximately 53 cells/mm3.
After 4 weeks of beta-carotene therapy, it rose to 76 cells/mm3.
However, it returned to approximately 53 cells/mm3 6 weeks after
treatment was stopped. A recommendation was made for
beta-carotene to be tried in larger groups of patients.
Bianchi-Santamaria and colleagues (1993) gave
60 mg per day of beta-carotene 20 days of each month for 21
months to 64 patients with AIDS-related complex, which is the
stage of HIV infection that occurs just before full-blown AIDS.
This is the study with by far the longest duration and also is
the largest and most recent. Mean CD4 count at baseline was
approximately 451 cells/mm3. After 21 months of beta-carotene
treatment, the mean CD4 count rose to approximately 519
cells/mm3, an increase of 15 percent. Normally, the mean CD4
count in these patients would be expected to drop. Furthermore,
the authors suggested that the beta-carotene accounted for the
apparent recovery of patients from asthenia, fever, nocturnal
sweating, diarrhea, and weight loss. Unfortunately, this study
did not have a control group.
Asthma, better termed hyperactive airway
disease, is an autoimmune disease characterized by increased
responsiveness of the tracheobronchial tree to exogenous and
endogenous stimuli. The hallmark of this illness is widespread
inflammation and narrowing of the tracheobronchial tree. This is
manifested clinically by dyspnea (shortness of breath), wheezing,
and cough, which generally occur simultaneously.
Asthma is typically managed with bronchodilator
therapy and/or anti-inflammatory drugs. However, currently used
pharmaceutical formulations for bronchodilation, such as
theophylline, have a narrow therapeutic margin because adverse
effects often occur at concentrations high enough to be effective
(Taburet and Schmit, 1994). In addition, prednisone, the most
common anti-inflammatory drug used to treat asthma, is also
associated with a variety of adverse side effects. Such limited
effectiveness of presently available treatments has recently
sparked research into less toxic, immune-enhancing nutritional
approaches to treating asthma. Data on the efficacy of vitamin C
and magnesium in the treatment of this condition are presented
Vitamin C. Bielory and Gandhi (1994) conducted
a comprehensive literature search of relevant English-language
papers pertaining to the use of vitamin C in in the treatment of
asthma and allergy and analyzed the studies according to their
design, inclusion and exclusion criteria, population studied,
variables or factors tested, method of intervention or treatment
with vitamin C, and results and conclusions. They found a number
of studies that support the use of vitamin C in asthma and
allergy. Significant results included positive effects of vitamin
C on pulmonary function tests; bronchoprovocation challenges with
methacholine, histamine, or allergens; improvement in white blood
cell function and motility; and a decrease in respiratory
infections. On the other hand, their review also revealed several
studies that did not support a beneficial role for vitamin C in
asthma and allergy. These studies did not report improvements in
pulmonary function tests or bronchoprovocation challenges or on
other reactivity or specific immunologic factors and levels.
From their review, the researchers concluded
that the majority of the studies were too short-term and assessed
immediate effects of vitamin C supplementation. Rather, long-term
supplementation with vitamin C or delayed effects need to be
examined for the studies to be valid. The researchers went on to
note that although the current literature does not support a
definite indication for the use of vitamin C in asthma and
allergy, the promising and positive studies were worth following
up. Furthermore, the researchers suggested, with a large portion
of health care dollars being spent on alternative medicine and
vitamin C in particular, further studies are needed to define its
role, if any, in the treatment of this condition.
Magnesium. First reported almost 50 years ago
(Haury, 1938), the efficacy of magnesium in the treatment of
bronchial asthma has received considerably more attention in the
past few years. Its bronchodilating effect was reported in
patients with mild asthmatic attacks, and when that was found
effective, applied to those with severe attacks (Okayama et al.,
1988). Intravenous magnesium sulfate was found to relieve
respiratory failure in asthmatic patients not responsive to
standard drug therapy (Hauser and Braun, 1991; McNamara et al.,
1989; Neves et al., 1991; Noppen et al., 1990; Okayama et al.,
1991; Skobeloff et al., 1989) and has been considered lifesaving
(Dellinger, 1991; Kuitert and Kletchko, 1991).
Not all published trials of magnesium treatment
of bronchial asthma, however, have been successful (Green and
Rothrock, 1992; Kufs, 1990). However, the protocols of those
studies reporting no therapeutic benefit of magnesium in asthma
patients have been criticized on the grounds that insufficient
dosages were used, with the result that the serum levels found
effective in the treatment of preeclampsia and eclampsia (see
below) were not achieved (Fesmire, 1993). Another criticism
leveled at the negative efficacy reports was that the study group
was too small for significance; this was countered by pointing
out that analysis of results from the first 40 patients indicated
withholding magnesium from comparably compromised patients would
be unethical, so the study was ended and the results were
reported (Skobeloff and McNamara, 1993).
Cancer. The rationale for the use of high
dosages of vitamins, particularly vitamin C, to treat cancer was
discussed in the beginning of this section. The following is a
review of more recent data that have emerged since the negative
results of the Mayo Clinic studies for vitamin C, as well as
quite intriguing data on the use of high dosages of coenzyme Q10
in the treatment of certain cancers.
Vitamin C. The possible value of vitamin C as
an adjuvant in cancer therapy is supported in animal and human
studies. Indeed, vitamin C, used in conjunction with other
treatment modalities, has been shown to improve the effectiveness
of those treatments (Meadows et al., 1991; Poydock, 1991; Tsao,
1991). Of equal interest, vitamin C supplementation has been
shown to reduce the toxicity of conventional chemotherapeutic
agents, such as adriamycin (Fujita et al., 1982), and to reduce
the toxicity and improve therapeutic gain of radiation therapy
(Okunieff, 1991). There also is evidence that some of the severe
toxicity associated with interleukin-2/LAK cell therapy may
result from the drastic reduction in plasma vitamin C levels that
this therapy causes (Marcus et al., 1987). Thus, these examples
suggest that the use of vitamin C or other nutrients as adjuncts
to therapy may reduce toxicity and thereby permit the use of more
effective doses of the therapeutic agent.
Coenzyme Q10. Recently, Lockwood and colleagues
(1994) treated 32 breast cancer patients with antioxidants, fatty
acids, and 90 mg of coenzyme Q10 (CoQ10) per day and reported
partial tumor regression in six patients. In one of the cases,
the dosage was increased to 390 mg per day and, reportedly,
within 2 months the tumor was no longer detectable by
mammography. Encouraged by this, Lockwood and colleagues treated
another patient with a verified breast tumor with 300 mg per day,
and after 3 months they could find no sign of remaining tumor.
Folkers reported that administration of this enzyme increases
levels of immunoglobulin G, an antibody that is known to
participate in antibody-dependent cellular toxicity against
virally infected cells and, possibly, against cancer cells
(Folkers et al., 1982, 1993). The same studies also showed
increases in T4 lymphocytes--the immune cells targeted and
destroyed by HIV infection--when CoQ10 was given with pyridoxine
to AIDS patients.
Arteriosclerosis, heart attacks, arrhythmias,
sudden cardiac death, strokes, and toxemias of pregnancy. Vitamin
E. Postoperative thromboembolism, a major complication of
surgery, involves the formation of blood clots in the deep veins
of an extremity. The clots can break off and travel to blood
vessels in the lungs, causing a pulmonary embolism that can be
fatal. This is often a major postoperative complication despite
the use of various treatments that are partially effective in
preventing it. As far back as the late 1940s, Alton Ochsner
repeatedly advocated the administration of vitamin E to prevent
postoperative thromboembolism. His vitamin E regimen consisted of
200 to 600 IU of alpha-tocopherol per day, administered
intramuscularly or by mouth, beginning no later than the day of
surgery and continuing through the postoperative period (Kay et
al., 1950; Ochsner, 1964, 1968; Ochsner et al., 1950a, 1950b,
1951). As late as 1968 he wrote, "For 15 years I have used
alpha-tocopherol (vitamin E) routinely in the treatment of
patients who have been subjected to trauma of any magnitude. None
of these patients have had pulmonary embolism" (Ochsner,
In 1981, Kanofsky and Kanofsky completed a
search of the American and British literature, which disclosed
six studies comparing a vitamin E-treated group with a control
group (Coon and Whitrock, 1951; Coon et al., 1952; Crump and
Heiskell, 1952; Ochsner et al., 1951; Kawahara, 1959; Moorman et
al., 1953; Wilson and Parry, 1954). All these controlled studies
were published between 1951 and 1959. That none of the studies
used a double-blind design is unfortunate, since the diagnosis of
deep-vein thrombosis or pulmonary embolism was primarily based on
the observations of clinicians, which can be easily influenced by
bias. However, Kanofsky and Kanofsky analyzed the data from the
six studies and found a highly statistically significant effect
from the vitamin E treatment. There was a twofold greater risk of
deep vein thrombosis, a sixfold greater risk of all pulmonary
embolism, and a ninefold greater risk of fatal pulmonary embolism
in the control group than in the vitamin E-treated group
(Kanofsky and Kanofsky, 1981). The authors postulated that the
physiological mechanism that might explain these results involved
the ability of vitamin E to inhibit platelet aggregation.
Magnesium. Magnesium also has anticoagulant
activity, acting directly on the steps involved in blood
coagulation, counteracting the procoagulant effect of calcium
(Greville and Lehmann, 1944; Herrmann et al., 1970; Seelig,
1993), and decreasing platelet clumping. In the 1950s there were
reports of use of magnesium to prevent and treat clinical
thrombotic conditions (Hackethal, 1951; Heinrich, 1957,
Schnitzler, 1957). Animal studies demonstrated that magnesium
supplements prevented formation of coronary artery thromboses
when the animals were fed a thrombogenic diet (Savoie et al.,
1973; Szelenyi et al., 1967). Case reports have been published of
patients with magnesium deficiency characterized by neuromuscular
disorders and whose thromboemboli were prevented from recurring
by magnesium supplements; when the supplements were discontinued,
the thromboemboli recurred (Dupont et al., 1969; Durlach, 1967).
Recent findings have demonstrated that magnesium inhibits blood
coagulation and arterial constriction by increasing the
production of factors with antithrombotic and vasodilating
activities by the inner lining (endothelium) of blood vessels.
These findings have shed light on magnesium's usefulness in both
eclampsia and heart attacks.
The anticoagulant activity of magnesium has
found practical application in microsurgery, in which local
application during the surgical procedure prevented thrombotic
and subsequent scarring lesions (Acland, 1972). When used
intravenously in dogs and rabbits with partially constricted
coronary arteries, magnesium prevented formation of microthrombi
distal to the partial occlusion, a finding considered pertinent
to human angina with and without blockage of coronary arteries
(Gretz et al., 1987).
Since the 1920s, large doses of magnesium
(producing blood levels as high as two to three times normal) had
been shown to be effective in the treatment of preeclampsia
(hypertension with proteinuria or edema, or both, due to the
influence of pregnancy or recent pregnancy) (Lazard, 1925).
Diuretics and anticonvulsants eventually replaced magnesium as
the preferred treatment for this condition, until studies showed
that magnesium treatment resulted in better outcomes, including
more live births (Zuspan and Ward, 1965) and was the more
appropriate treatment (Sibai, 1990).
It appears that adequate magnesium is necessary
to maintain the integrity of the inner lining of the blood vessel
and to increase its production of the vasodilating,
anti-platelet-aggregating (antithrombosis) substance (Briel et
al., 1987; Watson et al., 1986). This activity of magnesium in
inhibiting thrombosis has provided the rationale for its use in
patients who have had a heart attack. In a large, double-blind
study of 2,300 patients, called the second Leicester Intravenous
Magnesium Intervention Trial, half of the patients received an
intravenous injection of magnesium within three hours of a heart
attack. This was followed by a 24-hour magnesium infusion in a
dose sufficient to raise the blood level of magnesium to twice
that of normal levels. This treatment, which was given in
conjunction with the standard treatment for a heart attack,
reduced heart failure and mortality by 25 percent in comparison
with patients who received only the standard treatment (Woods et
al., 1992; Woods and Fletcher, 1994).
However, a much larger "megatrial" of
magnesium therapy in heart attack victims failed to find such an
effect (Casscells, 1994; Unsigned Commentary, 1994). It has been
proposed that the failure of the megatrial (called ISIS-4) to
find the lifesaving effect of magnesium in heart attack patients
may have been due to the institution of magnesium treatment only
after use of a clot-dissolving treatment. This resulted in a
delay of almost 8 hours before the magnesium was given. In
contrast, in the earlier study, the magnesium was given
immediately upon hospitalization. Thus, in ISIS-4, the magnesium
may have been given after the damage to the heart muscle was done
(Casscells, 1994; Woods and Fletcher, 1994).
Lymphedema. Lymphedema, a swelling of the arms
or legs resulting from pathology in the lymphatic system, often
can be disabling or even crippling. It has been estimated that 32
to 75 percent of women who undergo surgery for breast cancer will
have some chronic lymphedema of the arm on the affected side
(Casley-Smith and Casley-Smith, 1986). Unfortunately, the
treatment of this side effect of breast cancer surgery is often
neglected (Farncombe et al., 1994). Recently, however, there has
emerged an orthomolecular treatment for this condition using
benzopyrones. An overview of the studies utilizing this compound
for the treatment of lymphedema is presented below.
Benzopyrones. Since the mid-1980s, J.R.
Casley-Smith has recommended the use of large doses of
benzopyrones for the treatment of lymphedema. The benzopyrones,
though now frequently synthesized, were originally derived from
plants. The coumarins and flavonoids, such as rutin, are
benzopyrones. Szent-Gyorgi, the Nobel prize winner who isolated
vitamin C, discovered that a lack of benzopyrones caused greatly
increased capillary fragility and permeability (Casley-Smith and
Casley-Smith, 1986). Since then, benzopyrones have sometimes been
called "vitamin P" or "P factors."
Casley-Smith and colleagues believe that large
doses of benzopyrones alleviate lymphedema by stimulating
macrophage cells to break down unwanted proteins in the edema
fluid (Piller et al., 1988). Once excess protein is eliminated,
the edema fluid that it causes is no longer retained. Thus, they
believe that the benzopyrones safely change a slowly worsening
condition into a slowly improving one. There now are at least six
double-blind studies demonstrating that the benzopyrones are a
safe and effective treatment for lymphedema (Casley-Smith et al.,
1986, 1993; Cluzan and Pecking, 1989; Desprez-Curely et al.,
1985; Piller et al., 1985, 1988).
Unfortunately, no benzopyrones are available as
pharmaceuticals in the United States. Approval for drugs
containing rutin and other bioflavonoids was withdrawn in 1970 by
FDA on the grounds that there was no substantial evidence of the
effect they were purported to have. However, Casley-Smith has
argued that FDA used old, greatly outmoded data, which allegedly
showed that these drugs could not be absorbed (Casley-Smith and
Casley-Smith, 1986). He and others are emphatic that more recent
data show that the benzopyrones are absorbed and are effective.
Moreover, Casley-Smith and others believe that because
benzopyrones possess specific immune-stimulating properties and
can reduce every type of high-protein edema, they eventually will
become extremely valuable therapeutic agents in a wide variety of
clinical conditions (Casley-Smith and Casley-Smith, 1986).
Mental and neurological disorders. Despite
continued widespread skepticism among mainstream psychiatric
professionals about the effectiveness of vitamin therapy in the
treatment of neurological disorders, a small but growing number
of researchers persist in studying the use of vitamins for such
conditions. In fact, reports continue to surface on the
effectiveness of vitamins such as folic acid as well as a variety
of antioxidant vitamins in treating various mental and
Folic acid. Low serum folate has been reported
in 10 to 33 percent of psychiatric patients. In one retrospective
survey, psychiatric patients treated with folic acid spent less
time in the hospital and made significantly better social
recoveries than those in whom low serum folates were not treated
(Carney and Sheffield, 1970). Godfrey and colleagues recently
demonstrated that 41 (33 percent) of 123 patients with depression
or schizophrenia had borderline or definite folate deficiency.
These patients took part in a double-blind, placebo-controlled
trial of methylfolate (the actively transported form of folate),
taking 15 mg daily for 6 months in addition to standard
psychotropic medication. Among both depressed and schizophrenic
patients, methylfolate significantly improved clinical and social
recovery (Godfrey et al., 1990). These researchers speculate that
folate or methylfolate may have a direct pharmacological action
irrespective of whether the subjects were folate deficient.
Antioxidant therapy. Antioxidant therapy with
nutrients such as vitamin C, vitamin E, and beta-carotene has
been hypothesized as a treatment for schizophrenia (Lohr, 1991).
The hypothesis is based on evidence that the serum of
schizophrenics has high levels of lipid peroxides and the enzyme
superoxide dismutase. Both these substances are indicators of
unwanted oxidative products (mainly free radicals).
Just focusing on vitamin C, there is a
substantial body of animal and clinical data that ascorbic acid
may have an antipsychotic effect (Beauclair et al., 1987;
Giannini et al., 1987; Heikkila et al., 1983; Kanofsky et al.,
1988, 1989a; Milner, 1963; Rebec et al., 1984; Thomas and Zemp,
1977; Tolbert et al., 1979a, 1979b), which seems to be most
apparent when ascorbic acid is given in combination with
antipsychotic medication. A double-blind study showed that
vitamin C increases the antipsychotic effects of haloperidol in
treating PCP psychoses (Giannini et al., 1987). Observational
studies and one double-blind study have indicated a similar
adjunctive role for vitamin C in treating schizophrenia
(Beauclair et al., 1987; Kanofsky et al., 1989a, 1989b; Milner,
1963). No one has studied the simultaneous use of several
antioxidants in the treatment of schizophrenia, which seems a
worthwhile avenue of research (Kanofsky and Sandyk, 1992; Lohr,
Double-blind studies have shown that tardive
dyskinesia (a late-occurring, movement-disorder side effect of
antipsychotic medication) can be treated with vitamin E
supplementation. The therapeutic effect of vitamin E seems most
likely when it is introduced within several years after the onset
of the disorder (Adler et al., 1993; Egan et al., 1992; Elkashef
et al., 1990). Several studies of patients with Alzheimer's
disease have been performed in which brain tissue at autopsy
showed evidence of increased brain lipid peroxidation (Farooqui
et al., 1988; Hajimohammadreza and Brammer, 1990; Subbarao et
al., 1990). Conceivably, antioxidants such as vitamin C and
vitamin E might prevent this increase; however, much more
research needs to be done before this treatment could be
seriously considered (Lohr, 1991). In view of current evidence
that vitamin E, either alone or in combination with deprenyl (an
inhibitor of monoamine oxidase in the brain), fails to delay
continued neurological deterioration in Parkinson's disease
(Parkinson Study Group, 1993), it is also possible that to be
most effective, antioxidant therapy must be introduced very early
in the development of neurological and psychiatric
disorders--prior to the point at which irreversible cell damage
has occurred. A similar argument can be made with regard to the
effectiveness of orthomolecular therapy in schizophrenia itself.
Magnesium. A condition known as "latent
tetany" syndrome, which is seen in some patients with slight
magnesium deficiency, is characterized by depressive anxiety,
weakness, irritability, fatigue, and many ill-defined complaints
(Durlach, 1988; Fehlinger et al., 1987; Galland, 1991-1992). This
syndrome has characteristics that resemble premenstrual syndrome
as well as chronic fatigue syndrome, both of which have responded
favorably to supplementation with magnesium compounds alone or
with other nutritional supplements (Abraham and Lubran, 1981;
Stewart and Howard, 1986; London et al., 1991; Facchinetti et
There is evidence suggesting that magnesium
deficiency participates in the abnormalities of migraine
headaches and that migraines will respond to treatment with
magnesium (Swanson, 1988; Weaver, 1990). Transient ischemic
attacks, another disorder which like migraine is associated with
cerebral arterial spasms, has also been found to respond to
magnesium (Fauk et al. 1991). These clinical findings of
magnesium's protective effects against ischemia (loss of blood
flow) and hypoxia (oxygen deprivation) make it worthwhile to
examine the considerable animal evidence that magnesium
deficiency increases susceptibility to brain damage caused by
cerebral arterial spasm, arterial blockage (i.e., stroke), or
trauma (McIntosh et al., 1988; Blair et al., 1989; Okawa, 1992)
and that magnesium treatments offer the potential for minimizing
such brain damage (McIntosh et al., 1989; Vink, 1991-1992; Smith
et al., 1983).
Clinicians in Japan have shown in a small pilot
study that intravenous magnesium infusions improved the cerebral
flow of stroke victims (who before treatment had low magnesium
levels in their cerebrospinal fluid) (Iwasaki et al., 1989).
Indeed, 10 patients who received magnesium therapy had a better
return of normal cerebral functioning than did ten control
patients who did not receive magnesium after a stroke. Whether
prompt magnesium treatment after a stroke and/or after brain
trauma will improve the prognosis of such patient deserves
Selenium. In certain regions of the world,
including Great Britain and parts of the United States and
Canada, selenium levels in food are so low that the possibility
of subclinical deficiency (and a possibly related adverse effect
on mood) exists. Benton and Cook (1991) conducted a double-blind,
crossover trial of 50 subjects in ostensibly good health. They
were randomly assigned to receive a 100-microgram selenium tablet
or placebo each day for 5 weeks. After a 6-month washout, they
received the alternate treatment for 5 weeks. Benton and Cook
concluded that the intake of selenium tablets was associated with
an elevation of mood, particularly in subjects whose diets were
relatively deficient in the trace element.
Amino acids. A double-blind, randomized study
showed S-adenosylmethionine--the physiologically active form of
the amino acid methionine--to be a more rapidly acting
antidepressant than the pharmaceutical drug imipramine in
treating major depression (Bell et al., 1988). At the end of this
2-week study, 66 percent of the S-adenosylmethionine patients had
a clinically significant improvement in depressive symptoms
versus 22 percent of the imipramine patients. If
S-adenosylmethionine does turn out to be a more rapidly acting
drug--taking days rather than weeks to achieve results--this
characteristic may offer a considerable advantage in light of the
known risk of suicide during the early nonresponding phase of
treatment with most, if not all, other antidepressants.
Clinical trials of the amino acid glycine given
orally to schizophrenic patients have yielded conflicting
results. However, in the most recent double-blind study, Javitt
and colleagues (1994) showed a statistically significant
improvement in negative symptoms of schizophrenia when glycine
was added to conventional antipsychotic drug regimens. This
suggests that glycine may serve as a distinctive and valuable
adjunctive treatment for schizophrenia.
Essential fatty acids. Vaddadi and colleagues
(1989) reported the results of a double-blind crossover trial of
essential fatty acid supplementation in 48 predominantly
schizophrenic psychiatric patients. Active treatment produced
highly significant improvements in total psychopathology scores
and a significant improvement in memory.
This section is an overview of the theoretical
basis and available research on a variety of diets that are
advocated for the treatment of chronic conditions such as cancer,
cardiovascular disease, and food allergies. Virtually all of
these dietary interventions emphasize the intake of much more
produce (fresh and freshly prepared vegetables, fruits, whole
grains, and legumes), providing high nutrient density while at
the same time restricting such "empty" calories as
those provided by sweets, fats, and overprocessed foods. In these
diets, moreover, overall caloric intake tends to be lower than
that of the general U.S. population.
Nutrient modification for the treatment of
cancer. Cancer accounts for one of every five deaths in the
United States (American Cancer Society, 1990). More than 1
million cases of new cancers are diagnosed every year, and about
75 million, or one in three Americans now living, will eventually
have cancer (Public Health Service, 1990). Cancer is not one
disease but a constellation of more than 100 different diseases,
each characterized by the uncontrolled growth and spread of
abnormal cells. Cancer may strike at any age, though it does so
more frequently with advancing age. Although corroborative
intervention data are not yet available, it is estimated that 35
percent of cancer deaths may be related to diet (Eddy, 1986).
The rationale behind most dietary regimens for
the treatment of cancer--and for vegetarian, low-fat, high-fiber
dietary regimens in particular--is that if dietary excesses can
lead to the development of certain cancers, then such cancers may
be susceptible to dietary manipulation as well. These diets, for
the most part, share certain characteristics with the kinds of
foods currently recommended by mainstream groups, such as the
American Cancer Society (ACS), for lowering the risk of
developing cancer and heart disease. Recent ACS guidelines for
cancer prevention suggest reducing the intake of fat, alcohol,
and salt-cured and smoked foods while increasing the intake of
fruits, vegetables, and whole grains (Nixon, 1990). One way these
alternative dietary regimens for cancer differ, however, from
mainstream preventive recommendations is that they may emphasize
a few particular foods and limit or totally eliminate others.
In September 1990 the U.S. Congress Office of
Technology Assessment (OTA) completed a study of a number of
unconventional cancer treatments. Among these was a variety of
dietary regimens developed for the treatment of cancer and/or the
support of patients undergoing conventional cancer therapy. This
report, Unconventional Cancer Treatments, focused on three of the
most well-known dietary interventions for cancer: the Gerson
therapy, the Kelley regimen, and the macrobiotic diet. These
three regimens and a few others are reviewed below. Findings from
the OTA report as well as studies done since that report was
released are covered.
Gerson therapy. The Gerson therapy was
developed by physician Max Gerson in the early part of this
century. Gerson was born in Germany in 1881 and immigrated to the
United States in 1936. He received his New York medical license
in 1938 and his U.S. citizenship in 1944. He opened a private
medical practice in New York City and in 1946 also began treating
patients at nearby Gotham Hospital.
He gained renown in Germany through his success
in treating tuberculosis of the skin through low-salt dietary
management (Gerson, 1929). He then began testing modifications of
this regimen in other conditions, including pulmonary
tuberculosis (Gerson, 1934). He first used his diet for cancer in
1928, reportedly after a woman with a bile duct cancer that had
spread to her liver insisted that he put her on his diet despite
his reluctance to do so (Lerner, 1994). Much to his surprise,
Gerson wrote, the woman recovered (Gerson, 1958). Afterward,
Gerson tried variations and combinations of foods and other
agents on his patients, noted the ones who reacted favorably, and
adjusted subsequent patients' regimens accordingly (Gerson,
1978). By the time he came to America, he was focusing on
treating cancer patients.
In 1946 Gerson testified before a subcommittee
of the Senate Committee on Foreign Relations, which was holding a
hearing on a proposed bill to authorize increased Federal
spending for cancer research. Gerson reported to the Senate
committee that he had developed a dietary regimen that was
effective for the treatment of advanced cancer. According to the
historian Patricia Spain Ward, Gerson's testimony was supported
by the director of the Gotham Hospital, with which Gerson was
affiliated, as well as others in attendance (Ward, 1988). Gerson
described five patients in clinical detail and submitted written
case histories of those and five more patients who had been
treated with his regimen, in whom he had observed improvements in
"general body health" and, in some cases, tumor
reduction. In a later publication, Gerson noted that in six
additional patients his treatment appeared to reduce inflammation
around the tumors, relieve pain, improve psychological condition,
and provide at least temporary tumor regression (Gerson, 1949).
In the mid-1950s, Gerson first published explanations of the
components of his regimen and the rationale for their use, along
with some of the clinical outcomes he observed.
Gerson believed that his treatment regimen
reversed the conditions he thought necessary to sustain the
growth of malignant cells. He attached great importance to the
elimination of "toxins" from the body and the role of a
healthy liver in recovery from cancer. Gerson noted that if the
liver was damaged (e.g., by cancer or cirrhosis) the patient had
little chance of recovery on his or her treatment regimen
(Gerson, 1949, 1986). He observed that cancer patients who died
during treatment showed a marked degeneration of the liver, which
he presumed was due to the release of unspecified toxic factors
into the bloodstream by the process of tumor regression. He
believed that these toxic tumor-breakdown products poisoned the
liver and other vital organs (Cope, 1978).
Another central point of Gerson's approach
concerned the balance of potassium and sodium in the body. He
believed that an imbalance in the concentration of these
substances contributes to cancer-induced edema, a condition in
which cellular damage leads to infiltration by excess sodium and
water, failure of cellular transport mechanisms, subsequent
failure of cellular energy production, and, finally, loss of
resistance to cancer. Therefore, he sought to eliminate sodium in
patients' diets, supplement it with potassium, and thereby alter
the internal environment supporting the tumor (Gerson, 1954a,
At present, the Gerson therapy is an integrated
set of treatments that include the restriction of salt in
combination with potassium supplementation of the diet. Thyroid
supplements also are given to stimulate metabolism and cell
energy production. Hourly feedings of fresh, raw juices of
vegetables and fruits are given in addition to a basically
vegetarian diet. Fat intake is restricted (to lower intake of
potential tumor promotors), and protein is temporarily restricted
(to promote nonspecific, cell-mediated immunities). Coffee enemas
are provided to manage pain and to stimulate bowel and liver
enzymes that may increase the release of toxins (Gerson
Institute, undated-a). Other treatments beyond the ones specified
by Gerson have been added to the current protocol in recent
years. Gerson gave patients raw liver juice several times daily,
but the practice has been abandoned by current practitioners
because of bacteria in the liver juice that caused major
infections in some patients (Office of Technology Assessment,
Critics of the Gerson therapy point to the fact
that it is based on the beliefs of a physician who practiced many
years ago and whose knowledge of the cause of cancer was
rudimentary (Green, 1992). Proponents of the therapy argue,
rather, that Gerson was far ahead of his time; however, they also
note that many of Gerson's original assumptions and therapies
have been updated to take into account the latest scientific
evidence (Hildenbrand, 1986).
Because of such misconceptions about Gerson and
how his therapy is currently administered, proponents contend
that it has never been given a fair evaluation by mainstream
science. Furthermore, they argue that such myths and
misconceptions about the Gerson therapy are perpetuated by major
medical journals that routinely publish articles attacking the
basic tenets of the therapy while refusing to publish rebuttals
to such attacks (Lechner and Hildenbrand, 1994).
Research base. There have been several attempts
by a number of groups and individuals to assess the clinical
effects of the Gerson regimen. However, none have yet offered any
definitive results (Office of Technology Assessment, 1990). The
following is an overview of early and more recent cases.
In 1959, NCI reviewed 50 case histories
presented in Gerson's book, A Cancer Therapy: Results of Fifty
Cases. NCI concluded that in the majority of cases a number of
basic criteria were not met. NCI also concluded overall that
Gerson's data provided no demonstration of benefit (Avery, 1982;
U.S. Department of Health and Human Services, 1987). The Gerson
Institute, however, disputed NCI's findings and charged that NCI
had dismissed legitimate evidence on the basis of technicalities.
In addition, the Gerson Institute claimed that even though NCI
had indicated six cases were acceptable for further review and
another 20 needed further documentation, NCI's own records
indicate that such reviews were never done (Gerson Institute,
More recently, an exploratory study of the
clinical effects of some components of the Gerson regimen was
conducted by Peter Lechner, M.D., at the University Hospital of
Graz, Austria. This study used a modified Gerson therapy (i.e.,
liver juice and thyroid supplements were omitted, the number of
coffee enemas was limited, and a high-calorie beverage was added
to double energy consumption) as an adjunctive treatment. Lechner
reported that patients following the modified Gerson regimen
showed no side effects attributable to the treatment and did not
become malnourished. One of the patients with inoperable liver
metastases who followed the Gerson treatment showed a temporary
regression. In Lechner's opinion, there were subjective benefits
from the modified Gerson regimen: patients needed less pain
medication, were in better psychological condition, and
experienced less severe side effects from chemotherapy than did
control patients (Lechner and Kronberger, 1990).
Lechner's study also suggested that a modified
Gerson regimen might be effective in lowering rates of
postsurgical complications and secondary infections, increasing
tolerance of conventional radiotherapy and chemotherapy, reducing
reliance on analgesics, providing for an improved overall
psychological profile, retarding progress of liver metastases,
and improving the state of malignant effusions (Lechner and
A research team from the University of London
that visited the Mexican clinic offering the Gerson therapy (see
below) in 1989 on behalf of a British insurance company studied
27 cases in detail. Of those cases, 20 were considered not
assessible. Of the 7 assessible cases, 3 showed progressive
disease, 1 showed stable disease, and 3 (43 percent of the
accessible cases) were in regression. Moreover, the therapy
clearly provided a subjective benefit for the patients and their
families. In light of the poor prognosis of most of the patients
they observed at the clinic, the British team concluded that the
example of the Gerson therapy demonstrated a "way
forward" for the treatment of cancer (Sikora et al., 1990).
The Gerson Research Organization of San Diego
is currently conducting large retrospective reviews of treatment
outcomes of more than 5,400 patient charts, including 5-year
survival rates by stage (Hildenbrand et al., 1993), for patients
treated by the Mexican medical group Centro Hospitalario
Internacional del Pacifico, S.A. This facility, a semi-intensive
care hospital, has offered Gerson's treatment since 1976. The
review will include patients who either had no previous treatment
or failed previous treatment as well as patients who received
complementary conventional treatments.
Kelley regimen for cancer. In the 1960s,
William Donald Kelley, an orthodontist by training, developed and
publicized a nutritional program for cancer after reportedly
being told by his doctor that he had metastatic pancreatic cancer
and had only 2 months to live (Office of Technology Assessment,
1990). By trial and error, he self-administered doses of enzymes,
vitamins, and minerals to treat his cancer. After his recovery,
he applied his dietary program to his family; he also believed
that his wife and two of his three children had developed cancer
(Kelley, 1969). The Kelley regimen clearly derives from Gerson's.
Common elements include carrot juice, a basically vegetarian
diet, coffee enemas, and pancreatic enzymes, although pancreatic
enzymes play a more emphatic role in the Kelley treatment. The
Kelley regimen for cancer became one of the most widely known
unconventional cancer treatments. Although Kelley is no longer
practicing his treatment, the regimen has been continued in a
variety of forms by his followers.
One of the people who adopted the Kelley
regimen for the treatment of cancer patients was New York
physician Nicholas Gonzalez, M.D. Gonzalez has examined the
Kelley regimen and provided his own analysis of Kelley's
individual metabolic profiles. According to Gonzalez, Kelley
believed that human beings are of three genetically based types:
sympathetic dominants, parasympathetic dominants, and balanced
types. Sympathetic dominants, who have highly efficient and
developed sympathetic nervous systems but inefficient
parasympathetic nervous systems, evolved in tropical and
subtropical ecosystems, eating plant-based diets. Parasympathetic
dominants, in which the opposite is the case, evolved in colder
regions, eating meat-based diets. Balanced types, whose nervous
systems are equally developed, evolved in intermediate regions,
eating mixed diets (Office of Technology Assessment, 1990).
Kelley developed a diet for each type according
to the type's hypothesized historical origins. He had also traced
a characteristic path of "metabolic decline" for each
group when it consumed the wrong diet. He associated "hard
tumors" with severely compromised sympathetic dominants, and
"soft tumors" (cancers of the white blood cells and
lymph system) with severely compromised parasympathetic dominants
(Office of Technology Assessment, 1990).
As offered by Gonzalez, the Kelley program
stresses biodiversity, tailoring diets to individual needs and
ranging from purely vegetarian to diets requiring fatty red meat
several times daily. Patients consume many supplements--vitamins,
minerals, and trace elements--in 130 to 160 capsules daily.
Research base. In his 1987 manuscript One Man
Alone: An Investigation of Nutrition, Cancer, and William Donald
Kelley, Gonzalez presented case histories of 50 patients he
selected from his files (Gonzalez, 1987). This case series has
been singled out by proponents as one of the most convincing in
support of an unconventional cancer treatment (Office of
Technology Assessment, 1990).
In 1990, OTA attempted to find out whether the
information presented in these cases would be convincing to the
medical community by asking six physicians on its advisory panel
to review the cases; three of the physicians supported some
unconventional treatments, though none was associated with Kelley
or Gonzalez, and the other three were mainstream oncologists.
Fifteen cases were judged by the reviewers generally supportive
of some unconventional medicine as definitely showing a positive
effect from the Kelley program; in contrast, the mainstream
oncologists found that 13 of these 15 were unconvincing and that
2 were unusual (Office of Technology Assessment, 1990).
Another nine cases were judged unusual or
suggestive by the supportive group, and unconvincing by the
mainstream group. Another 14 cases were judged by the supportive
physicians as having been helped by a combination of the Kelley
regimen and mainstream cancer therapy; the mainstream group found
12 of these cases unconvincing and 2 unusual. Finally, 12 cases
were considered unconvincing by both groups of physicians. The
different interpretations of these cases by physicians who are
open to unconventional medicine and those who are not illustrates
the difficulty in evaluating therapies that fall outside the
bounds of conventional medical wisdom.
Gonzalez recently submitted to NCI a
meticulously documented best case series (Friedman, 1993). At
least 6 of the 24 cases reportedly document complete remissions
of cancers, 5 of them metastatic to various sites including
liver, pleura, brain, and bone. Two additional cases reportedly
document partial remissions.
Macrobiotic diet for cancer. The philosophy and
general components of the "standard macrobiotic diet"
are described below in the "Alternative Dietary Lifestyles
and Cultural Diets" section of this chapter. In the area of
cancer management and treatment, the macrobiotic philosophy holds
that the development of cancer is determined by dietary,
environmental, social, and personal factors; by extension,
existing cancers may be influenced by the same factors. The
development of cancer is described as a long-term, multistep
process that begins well in advance of actual tumor formation
(Kushi and Jack, 1983).
According to macrobiotic teachings, accumulated
toxins result from overconsumption of milk, cheese, meat, eggs,
and other fatty, oily, or greasy foods. Also included in this
list are foods with a cooling or freezing effect, such as ice
cream, soft drinks, and orange juice (Kushi and Jack, 1983).
Macrobiotics uses the traditional oriental concepts of yin
(expansive) and yang (contractive) to devise a framework for
explaining and formulating a set of dietary recommendations to
treat each type of cancer.
A macrobiotic approach to treating cancer would
first classify each patient's illness as predominantly yin or
yang, or sometimes a combination of both, partly on the basis of
the location of the primary tumor in the body and the location of
the tumor in the particular organ. In general, tumors in
peripheral or upper parts of the body or in hollow, expanded
organs are considered yin; examples include lymphoma, leukemia,
Hodgkin's disease, and tumors of the mouth (except tongue),
esophagus, upper stomach, breast, skin, and outer regions of the
brain. Tumors in lower or deeper parts of the body or in more
compact organs are considered yang; examples include cancers of
the colon, rectum, prostate, ovaries, bone, pancreas, and inner
regions of the brain. Cancers thought to result from a
combination of yin and yang forces include melanoma (skin cancer)
and cancers of the lung, bladder, kidney, lower stomach, uterus,
spleen, liver, and tongue (Kushi and Jack, 1983).
For cancers classified as predominantly yang,
the standard macrobiotic diet is recommended, with slight
emphasis on yin foods. The same diet is recommended for
yin-classified cancers, with a slight emphasis on yang foods.
Patients with cancers resulting from both yin and yang imbalances
are advised to follow "a central way of eating," as
suggested in the standard macrobiotic diet. Different cooking
styles also are recommended on the basis of this disease
classification (Kushi and Jack, 1983).
Research base. The available information on the
effectiveness of the macrobiotic diet for treating cancer comes
from retrospective case reviews and anecdotal reports, some of
which come from the popular literature, and two unpublished
retrospective studies (Office of Technology Assessment, 1990). A
number of individual accounts of patients who attributed their
recovery from cancer to their adherence to a macrobiotic diet
have been written in recent years.
In one unpublished retrospective study, Carter
and colleagues (1990) compared survival times between 23
pancreatic cancer patients maintained on a macrobiotic diet and
similar patients who received conventional cancer therapy. The
authors reported that the mean survival (the average) and the
median survival (the point in time after diagnosis by which half
the group died) was significantly longer for the macrobiotically
maintained patients. A followup study by Carter also showed
improved survival time for 11 patients with prostate cancer on a
macrobiotic diet. However, OTA pointed out that the studies had
design flaws that may have overstated the effect (Office of
Technology Assessment, 1990).
In another unpublished manuscript, Newbold
(undated) presented six case histories of patients with advanced
cancer who adopted a macrobiotic diet in addition to using
mainstream treatment. These cases were well described medically,
including references to appropriate diagnostic tests (all but one
case was definitely biopsy proven) and followup scans and tests
(Office of Technology Assessment, 1990).
As in the review of the Kelley regimen, when
OTA asked its independent advisory panel of six physicians to
review Newbold's cases the three mainstream reviewers did not
find any of the cases compelling, while two physicians who were
open to unconventional therapies were more positive about the
outcomes. One concluded that five of the six cases (all except
the one without the biopsy-proven diagnosis) showed positive
effects from the macrobiotic diet. The remaining physician found
two cases that seemed "legitimate," two "highly
suggestive," one "suggestive," and one not
convincing (Office of Technology Assessment, 1990).
The retrospective studies presented by Carter
and Newbold's case histories were later combined and published in
the Journal of the American College of Nutrition (Carter et al.,
1993). Although the design flaws noted by OTA were still extant
in the study, an accompanying editorial suggested that these
findings may provide clues to a new approach to the dietary
management of cancer (Weisburger, 1993). The editorial stated
that the macrobiotic diet has "been construed by classical
nutritionists as inadequate. . . . Yet, the application to
control the growth of cancer may actually be based on the fact
that it is an inadequate diet." The editorial continued by
stating that "Perhaps the time has come to teach
nutritionists that, in some instances, a nutritional regimen
clearly deficient in growth promoting substances might actually
be helpful in controlling otherwise untreatable diseases."
Additional cancer diets. Additional cancer
diets reviewed by the Office of Technology Assessment included
the Livingston/Wheeler regimen and the Wigmore treatment.
Livingston/Wheeler regimen. This regimen is
mentioned here because its practitioners advocate diet as a means
of potentiating antitumor immunity. Based on Dr. Virginia
Livingston's observation of a putative cancer-causing
microorganism, the treatment combines vaccines, bacterial
reagents, a patented retinoic acid, intravenously administered
vitamins, long-term use of antibiotics, and a modified Gerson
diet with coffee enemas. Her San Diego-based clinic has
continued, after her death, to offer her treatment.
Wigmore treatment. This treatment is an
empirically developed dietary regimen (Wigmore, 1985) that uses
seed sprouts, wheat grass juice, and uncooked vegetables and
fruits. The available literature contains accounts of positive
outcomes in cancer, but they are presented without conventional
documentation, making it impossible to confirm or deny them.
Although advocates have gone to considerable lengths to present
supportive literature for their practices (Wigmore, 1993), formal
clinical testing has been limited to studies of the reversible,
short-term effects of the diet on serum lipids, lipoprotein, and
apolipoprotein (W. Ling et al., 1992), which findings are
consistent with, if less extensive than, those of similar
fat-restricted, basically vegetarian diets (Walford et al.,
Fat-modified diets for treatment of
cardiovascular disease and diabetes. Coronary artery disease is
the leading cause of death and disability in the United States.
Seven million people, nearly 3 percent of the U.S. population,
have clinical coronary heart disease. Every year, 1.5 million
Americans have acute heart attacks, which kill approximately
520,000 persons, 247,000 of whom are women (American Heart
Association, 1991). In fact, cardiovascular diseases--primarily
coronary heart disease and stroke--kill nearly as many Americans
each year as all other diseases combined (National Center for
Health Statistics, 1990). Furthermore, more than 60 million
Americans, or 30 percent of the adult population, currently have
high blood pressure (National Heart, Lung, and Blood Institute,
1985), which makes them prime candidates for stroke and heart or
Balloon angioplasty (inserting a tiny balloon
into the circulatory system and inflating it to open up a
plaque-blocked artery) is performed approximately 300,000 times a
year in the United States. Although angioplasty provides
immediate and possibly lifesaving relief for many patients, it is
not a long-term solution. There is no evidence that angioplasty
does anything to prevent future angina (severe chest pain) or
heart attacks, and about 30 to 40 percent of all
angioplasty-treated vessels block up again within 6 months,
meaning another angioplasty must be performed (Becker, 1991).
Each angioplasty procedure costs about $20,000.
For the most severe cases of heart disease,
surgeons remove veins (usually from the legs) and use them to
"detour," or bypass, around the clogged arteries of the
heart. Even though people who undergo bypass operations
experience a reduction in chest pain, the benefits of this
surgery, which costs approximately $30,000, often wear off
Researchers have known for several decades that
a proper diet may prevent the onset of cardiovascular disease.
However, once an individual develops this chronic condition,
surgery and drugs have been considered the only available methods
in mainstream medicine for trying to reverse its effects (Califf
et al., 1989). Only recently has diet been considered an
alternative to drugs and surgery for treating cardiovascular
disease. In the mid-1970s, Nathan Pritikin began using an
extremely low-fat, high-fiber diet along with exercise to treat
heart disease patients and showed that he could lessen their
clinical symptoms. Then in the late 1980s, San Francisco
physician Dean Ornish set out to do the same. However, Ornish was
armed with a powerful new tool: the angiogram, which is an
interior picture of patients' blood vessels. Using
"before" and "after" angiograms, Ornish was
able to see how changes in diet and lifestyle affected the status
of the blockage, or plaque, in the artery. The Pritikin and
Ornish diets are described below.
Pritikin diet. The diet is named after the man
who developed it, Nathan Pritikin, who had been told by his
cardiologist that he was at great risk of death from myocardial
infarction. Therefore, he patterned for himself a diet modeled
after a vegetarian diet followed by the people of Uganda, who
were shown to be essentially free from death by heart attacks
(Martin, 1991). In the late 1960s, after a few years on this
diet, Pritikin decided that it had saved his life and founded his
clinic in Santa Monica to treat cardiac patents.
The Pritikin diet is basically vegetarian, high
in complex carbohydrates and fiber, low in cholesterol, and
extremely low in fat (less than 10 percent of daily calories).
The Pritikin diet also requires 45 minutes of walking daily.
Although this diet and exercise program can be followed
completely on an outpatient basis, the Pritikin Longevity Center
in Santa Monica recommends that patients attend a 26-day program
to learn how to prepare their new type of meals and practice new
daily exercise and living habits.
Ornish diet. This diet was developed by Dean
Ornish, M.D., an assistant clinical professor of medicine at the
University of California, San Francisco. The Ornish diet is
basically vegetarian, allowing no meat, poultry, or fish, and
permitting only the white of eggs. Also, no nuts, caffeine, or
dairy products, except a cup a day of nonfat milk or yogurt, are
allowed, and no oil or fat is permitted--not even for cooking.
Two ounces of alcohol a day are allowed. Providing an average of
about 1,800 calories a day, the diet provides 75 percent of its
calories from carbohydrates and less than 10 percent from fat
(Ornish, 1990). The American Heart Association's recommended
adult "prudent diet" calls for total fat of less than
30 percent, which Ornish feels is not really low enough, even for
healthy adults, but especially not for people trying to reverse
atherosclerosis (Ornish, 1990). Ornish provides his patients all
their lunch and dinner meals, precooked, packed in Tupperware,
and handed out a week's worth at a time.
In many ways, the Ornish diet is similar to the
Pritikin diet. Both are basically vegetarian (although Pritikin
does allow 85 grams of chicken or fish per week), high in complex
carbohydrates, high in fiber, low in cholesterol, and extremely
low in fat (less than 10 percent of daily calories). However,
Ornish's program--run on an outpatient basis--calls for stress
reduction practices in addition to the diet and emphasizes
emotional social support systems, particularly between members of
the group. It also requires daily stretching and an hour's walk
three times a week.
Research base. The following is an overview of
the available research on these two ultra-low-fat dietary
Pritikin diet. In a study of men taking the
Pritikin 26-day course, all 21 participants reduced their
cholesterol level, 19 reduced their triglyceride level, and 16
had a reduction in their estradiol level (Rosenthal et al.,
In another study assessing the effectiveness of
the Pritikin diet and exercise program on cardiovascular
hemodynamics, 20 subjects were divided in two groups
(active/treatment and control). These data were compared to a
group of 10 healthy individuals not involved in the program.
Hemodynamic parameters were collected at admission and at the end
of the 26-day program. In obese and hypertensive subjects not on
medication who followed the Pritikin program, the cardiac index
increased by 10 percent, mean arterial pressure decreased by 5
percent, and the systemic vascular resistance index decreased by
18 percent. Little change was seen in controls. There also was an
improvement in ventricular performance (Mattar et al., 1990).
The Pritikin diet has also been studied in
connection with adult-onset diabetes mellitus and peripheral
vascular disease. Studies suggest that it may show promise in
controlling newly diagnosed cases of adult-onset diabetes without
drugs. One study (Barnard et al., 1982) evaluated 60 patients who
had completed the Pritikin 26-day program. Of the 23 who were
taking oral hypoglycemic agents upon entry, all but 2 were off
medication by the end of the program. Of the 17 patients who were
taking insulin, all but 4 were off medication at discharge. Two
of those 4 had their insulin reduced by 50 percent, while the
remaining 2 had no major change in their insulin dosage. Fasting
blood glucose levels were significantly reduced in all patients;
serum cholesterol levels were similarly reduced, as were
triglyceride levels. The group as a whole lost an average of 4.3
kg of body weight and achieved 40.5 percent of their desired
weight loss. Maximum work capacity increased significantly, while
daily walking increased from approximately 11.7 minutes a day to
approximately 103 minutes.
In another study, University of California, Los
Angeles (UCLA) investigator Dr. James R. Barnard put 650 diabetic
patients on the Pritikin diet. After 3 weeks, some 76 percent of
the newly diagnosed diabetics, along with 70 percent of those on
oral agents, had normal glucose levels (Barnard et al., 1992).
However, only 40 percent of those already receiving insulin
responded to the diet. According to Barnard, muscles, which may
become severely insulin resistant during drug treatment, respond
to exercise and a low-fat diet. In contrast, drugs may eventually
weaken the pancreas while failing to reduce physically and
financially devastating vascular complications (e.g.,
deterioration of eyes and kidneys).
Ornish diet. In what is now known as the
Lifestyle Heart Trial, in the late 1970s and early 1980s Ornish
conducted a series of trials in which patients with confirmed
heart disease were placed on a diet and lifestyle modification
program. In the first study, after 30 days people reported a
substantial reduction in frequency of angina (heart pain), and
many were pain free. Cholesterol levels were down about 20
percent, and high blood pressure was reduced (Ornish et al.,
1979). In a followup study in the early 1980s, Ornish reported
that 30 days of his regimen were enough to improve blood flow to
the heart in some patients and that patients could exercise
almost 50 percent more, on average, than they could before
beginning the treatment (Ornish et al., 1983).
Finally, in a prospective, randomized,
controlled trial to determine the effectiveness of his program
over a longer time, Ornish and his colleagues put 28 men and
women whose arteries were partially blocked on his program for a
full year. Twenty other patients were assigned to a "usual
care" group. After 1 year, without the use of lipid-lowering
drugs, patients in the experimental group (i.e., receiving the
Ornish treatment) reported a 91-percent reduction in the
frequency of angina, a 42-percent reduction in the duration of
angina, and a 28-percent reduction in the severity of angina. In
contrast, control group patients reported a 165-percent rise in
frequency, a 95-percent rise in duration, and a 39-percent rise
in severity of angina (Ornish et al., 1990).
Patients in the experimental group also showed
a significant overall regression, or reduction, of coronary
atherosclerosis (blocked arteries) as measured by angiograms. In
contrast, patients in the usual care group had a significant
overall progression, or worsening, of their coronary
atherosclerosis. This finding led Ornish to conclude that the
conventional recommendations for patients with heart disease,
such as a 30-percent fat diet, are not sufficient to bring about
an improvement in many patients.
Ornish has never tested separately each
component of his multifaceted program, so it is impossible to be
sure which component contributed most to the improvements. If it
was the dietary regimen that led to the improvements, it is a
regimen that most Americans would have a hard time following,
admits Ornish (Schardt, 1993). However, some researchers believe
that it does not take such a radically restricted diet to start
reversing the effects of heart disease. In a study in Germany, 56
men suffering from angina caused by partially blocked arteries
were placed on a reduced-fat diet (less than 20 percent of
calories from fat, 7 percent of calories from saturated fat, and
200 mg of cholesterol a day). As in the Ornish program, they also
participated in an exercise program. After a year, angiograms
showed that the blockages in 32 percent of the men on the low-fat
diet had improved, compared with just 17 percent in the control
group (Schuler et al., 1992).
In addition, in the late 1980s, researchers in
Britain placed 26 men with partially blocked arteries and
elevated blood cholesterol on carefully monitored diets and
reduced their fat intake to 27 percent of calories--about
three-fourths of what the average American eats. The diet's
saturated fat and cholesterol amounts also were substantially
less than most Americans eat, while its fiber content was
slightly higher. Over the next 3 years, the men on the
fat-restricted diet suffered only one-third as many deaths, heart
attacks, and strokes as men in the control group--who were not
told what to eat, and whose diets were not monitored (Watts et
al., 1992). Furthermore, angiograms showed that the openings in
the arteries of 38 percent of the men who changed their diets
became slightly larger.
Food elimination diets for treatment of food
allergies. Allergies to food, or food intolerance, have become a
major area of research in recent years. Many of the researchers
involved in this research specialize in environmental medicine
(see the "Alternative Systems of Medical Practice"
chapter), which is the science of assessing the impact of such
environmental factors as chemicals, foods, and inhalants on
health. It provides an understanding of the interface between the
external environment and the biological function of the
Dietary management of food allergies is based
on avoidance of food antigens and the 4-day rotary diversified
diet. With the rotary diet and avoidance of repetitive food
exposures, it is possible to reduce sensitivity to foods and
hasten recovery from food allergies. Nutritional supplements are
prescribed as indicated by objective nutritional testing and the
symptoms of the patient.
Research base. Miller (1977) studied eight
chronically ill food-sensitive patients who were tested with
provocation-neutralization techniques. The patients were treated
with injections of allergy extracts and compared to those treated
with placebos. In a rigidly controlled study, King (1988) showed
a correlation between oral food challenge and
provocation-neutralization testing. Treatment using results from
this testing showed significant symptom relief. Using
neutralization therapy, Rea and colleagues (1984) found
significant improvement in 20 patients with known food
sensitivity in signs and symptoms of allergy reactions to certain
Food intolerance is also being studied as a
causal or contributing factor in rheumatoid arthritis. In a
clinical trial in Norway, Kjeldsen-Kragh and colleagues (1991)
found that fasting followed by dietary restriction could relieve
the symptoms of rheumatoid arthritis on a long-term basis. They
subjected 27 rheumatoid arthritis patients to a 7-to 10-day fast
(except for herbal teas, garlic, vegetable broth, a decoction of
potatoes and parsley, and extracts from carrots, beets, and
celery) followed by 1 year of an individually adjusted vegetarian
diet. The diet-restricted patients stayed on a Norwegian health
farm the first 4 weeks of the study. A control group of 26
patients stayed in a convalescent home for 4 weeks but ate an
ordinary diet throughout the trial.
After 4 weeks, the diet group showed a decrease
in pain score; a significant decrease in pain, morning stiffness,
and the number of tender and swollen joints; and improved grip
strength and ability to articulate the joints. There was also a
significant improvement in a number of biochemical markers
associated with inflammation. These improvements were maintained
throughout the year. In contrast, the control group showed a
decrease in pain score after its stay in the convalescent home,
but none of the other indices improved. At the end of the study
the conditions of the control patients had deteriorated.
This study suggests that there is a food
allergy component to rheumatoid arthritis and that food
restriction appears to be a useful supplement to the conventional
medical treatment of rheumatoid arthritis. Darlington and
colleagues (1986) and Beri and colleagues (1988) obtained similar
results, but their studies lasted only 3 months.
There is also evidence that food elimination
diets may benefit many children with hyperactivity (Kanofsky,
1986). Several research teams have used double-blind designs to
demonstrate this point. The Institute of Child Health and
Hospital for Sick Children in London undertook a randomized,
crossover, placebo-controlled trial to evaluate the effect of
diet on the development of hyperactivity (Egger et al., 1985).
The first phase of the study consisted of placing 76 hyperactive
children on a food elimination diet. The presupposition was that
individuals can be sensitive to a food or food additive in their
diet and that improvement occurs when the offending foods or food
additives are removed from the diet. At the end of the first
phase of the study, 62 of the 76 children (82 percent) improved
on the diet, and a normal range of behavior was achieved in 21
(29 percent) of them. In addition to overactivity, other symptoms
such as headaches, abdominal pain, antisocial behavior, and fits
were also often alleviated.
In all, 48 foods were implicated as
contributing to hyperactivity in the young patients. However, 34
of the 50 children for whom full data are available reacted to
fewer than 7 foods. Two reacted to 30 foods. Five patients were
also noted with symptoms from such inhalants as pollen, perfume,
and house dust. Foods that frequently caused problems included
cow's milk (64 percent of subjects tested), chocolate (59
percent), wheat (49 percent), and oranges (45 percent).
The second phase of the study included 28
children from the original group, who entered into a
double-blind, crossover, placebo-controlled trial that
reintroduced one incriminated food. Symptoms returned or were
exacerbated much more often when patients were on active material
than on placebo. One of the most interesting findings of the
study is that the artificial food coloring tartrazine and the
preservative benzoic acid were the commonest food items causing a
reaction. The behavior of 79 percent of the 34 children tested
deteriorated when tartrazine or benzoic acid was reintroduced
into their diet. These findings are compatible with the work of
Dr. Benjamin Feingold, the San Francisco allergist who implicated
tartrazine and other artificial food additives in children's
diets as contributors to hyperactivity. It is worth noting that
the same London group also published a study stating that 93
percent of 88 children with severe, frequent migraines recovered
on a diet that eliminated foods and food additives that had been
shown to cause symptoms (Egger et al., 1983).
Some confirmation for the food elimination
treatment for hyperkinesis was provided by Kaplan and colleagues
(1989). In their study, 10 of 24 hyperactive children exhibited
approximately a 50-percent improvement in behavior when placed on
an elimination diet that was not as restrictive as the London
A number of alternative dietary lifestyles
throughout the United States and the world are believed to
increase resistance to illness. Although some diets, such as
macrobiotics, have been intentionally developed in the past
half-century, others have evolved more naturally over the
An "alternative lifestyle" diet can
be described as any diet that differs from the mainstream
American diet. Such diets include various forms of vegetarianism
and diets with emphasis on "natural,"
"unprocessed," and/or other health foods in varying
degrees. Others are drawn from other societies around the world,
such as the "Mediterranean" diet.
Historically, there has been much skepticism
among some health professionals about such diets. For example,
when the vegetarian movement started in the United States about
50 years ago, people questioned whether adults subsisting on such
diets could even do a full day's work and still survive (Krey,
1982). However, generations of people around the world have now
grown up on these diets, helping to dispel such myths.
Furthermore, many individuals and population groups have
practiced vegetarianism on a long-term basis and have
demonstrated excellent health (American Academy of Pediatrics,
1977). Indeed, the case against such diets has been largely
cultural and economic (see the section "Barriers and Key
Issues Related to Diet and Nutrition" in this chapter).
Vegetarian diets. Vegetarian diets are among
the most common of alternative diets in the United States today.
The degree of vegetarianism can vary widely, ranging from those
who eat red meat infrequently to those who totally exclude any
animal-derived foods, such as dairy products or eggs, from their
diet. Vegetarianism is often categorized according to the extent
of these restrictions. For example, people who consume dairy
products and eggs but not other animal foods are referred to as
lacto-ovo-vegetarians, while people who avoid all animal products
are referred to as vegans. Studies of vegetarians in the United
States and other industrialized nations probably provide the most
extensive support for the idea that alternative dietary habits
can favorably influence the incidence and pathology of disease.
This section focuses on the nutritional aspects
of the two most widely studied variations on the vegetarian diet:
the one followed by adherents of the Seventh-Day Adventist
Church, and the macrobiotic diet. The health-related data from
people eating these diets are compared with data taken from
individuals in the general U.S. population.
Seventh-Day Adventists. The Seventh-Day
Adventists are a Protestant sect that among other things preaches
a clean, wholesome lifestyle and admonishes against eating animal
flesh (i.e., red meat, poultry, fish). Thus, Seventh-Day
Adventists are for the most part lacto-ovo-vegetarians. They also
abstain from alcohol, tobacco, and caffeine-containing beverages,
such as coffee and tea. Even though they avoid meat, Seventh-Day
Adventists' diets are not substantially lower in fat intake than
the typical American diet. For example, in one survey of
lacto-ovo-vegetarian Seventh-Day Adventists, total fat intake
averaged 36 percent of energy versus 37 percent for the average
American (Phillips et al., 1983).
Macrobiotic diet. Along with Seventh-Day
Adventists, people who consume a macrobiotic diet have been
studied extensively to examine associations with disease risk
factors. In addition, macrobiotic diets are among the most
popular alternative dietary therapies for cancer and other
chronic diseases (Cassileth et al., 1984).
The earliest version of the macrobiotic diet,
termed the "zen macrobiotic diet," originated with the
lecturer-philosopher Georges Ohsawa (1893-1966), the pen name for
Yukikaza Sakurazawa, a Japanese teacher who studied the writings
of Japanese physician Sagen Ishikuzuka (1850-1910). Ohsawa is
said to have cured himself of serious illness by changing from
the modern refined diet then sweeping Japan to a simple diet of
brown rice, miso soup, sea vegetables, and other traditional
foods. He initiated the development of macrobiotic philosophy,
reportedly integrating elements of Eastern and Western
perspectives with "holistic" perspectives on science
and medicine. Ohsawa made his first of several visits to the
United States in 1959.
Ohsawa outlined 10 stages of diet (designated
by numbers -3 to +7). Diet -3 consists of 10 percent cereal
grains, 30 percent vegetables, 10 percent soups, 30 percent
animal products, 15 percent salads and fruits, 5 percent
desserts, and beverages "as little as possible." With
each higher number diet, Ohsawa reduced the percentages of foods
from some categories or eliminated the category entirely and
increased others, so that in the +3 diet, for example, 60 percent
was cereals, 30 percent was vegetables, and 10 percent was soups.
Since the early 1970s, the macrobiotic movement
in the United States has been under the leadership of Michio
Kushi. Kushi, who studied with Ohsawa and came to the United
States from Japan in 1949, preserved elements of Ohsawa's
philosophy while incorporating a variety of broader and more
complex components into macrobiotic philosophy and practice. Most
notably, Ohsawa's 10-phase dietary levels were replaced with the
general "standard macrobiotic diet," which Kushi
described in detail in his 1983 book, The Cancer Prevention Diet
(Kushi and Jack, 1983).
Unlike Seventh-Day Adventists, whose vegetarian
diets usually include dairy products and eggs, the standard
macrobiotic diet as practiced today tends to minimize consumption
of all animal products except fish (M. Kushi, 1977, 1983). Thus
the macrobiotic diet is predominantly vegan, with an emphasis on
whole cereal grains and vegetables, preferably organically grown.
As a result, it tends to be relatively high in complex
carbohydrates and low in fat content (and, therefore, calories)
in comparison with the standard American diet. One survey of 50
adults consuming a macrobiotic diet demonstrated that fat intake
averaged 23 percent of energy, saturated fat intake averaged 9
percent of energy, and carbohydrate intake averaged 65 percent of
energy (L. Kushi et al., 1988).
Research base. The following is an overview of
the available research on the health-promoting and
disease-preventing effects of the Seventh-Day Adventist and
Seventh-Day Adventist diet. Despite their
relatively high fat intake, Seventh-Day Adventists have less
heart disease and incidence of some cancers than occurs in the
general U.S. population. For example, Seventh-Day Adventists who
eat little or no red meat have a lower death rate from heart
disease than the general U.S. population (Phillips et al., 1978;
Snowdon et al., 1984a). Indeed, studies on Seventh-Day Adventist
males have shown that their serum cholesterol levels were lower
and that the first heart attack occurred almost a decade later
than average. The incidence of heart disease was only 60 percent
as high as that of a control group in California (Register and
Sonnenberg, 1973). Abstinence from tobacco and alcohol also may
have contributed to this effect.
Studies comparing Seventh-Day Adventists with
non-Adventists demonstrate that the former tend to have lower
blood pressure levels as well. For example, in one study in which
age, sex, and body size were taken into account, blood pressure
levels for vegetarian Seventh-Day Adventists averaged 128.7 mm Hg
systolic and 76.2 mm Hg diastolic versus nonvegetarians' average
levels of 139.3 mm Hg systolic and 84.5 mm Hg diastolic
(Armstrong et al., 1977). Similar findings were seen in other
studies comparing vegetarian and nonvegetarian Seventh-Day
Adventists (Melby et al., 1989).
Another study comparing blood pressure levels
of vegetarian Seventh-Day Adventists with nonvegetarian Mormons,
who similarly avoid tobacco and alcohol, demonstrated that the
Seventh-Day Adventists still had lower blood pressure levels
(Rouse et al., 1982). Comparisons of California Seventh-Day
Adventists with their non-Adventist neighbors also demonstrated
that the Adventists had lower LDL cholesterol levels (Fraser,
The overall cancer death rate of male
Seventh-Day Adventists is only about half that of the overall
cancer death rate of the U.S. general population, and the overall
cancer death rate of female Seventh-Day Adventists is about 70
percent of that of the general population (Phillips et al.,
1980). The lower death rates apply not only to those cancer sites
known to be associated with cigarette smoking (e.g., lungs), but
also to other sites such as the breast. In fact, Adventists have
80 to 90 percent of the general population's breast cancer death
rate and only 50 to 60 percent of the colon and rectal cancer
death rate (Phillips et al., 1980). These observations suggest
that smoking habits alone cannot explain the difference between
cancer death rates of Seventh-Day Adventists and those of the
The results of other prospective dietary
studies among Seventh-Day Adventists are mixed when vegetarians
are compared with nonvegetarians. For instance, there appears to
be little relationship between such dietary variables as total
fat or animal fat intake with risk of breast cancer (Mills et
al., 1988, 1989a). However, in two prospective cohort studies,
Seventh-Day Adventists who rarely consumed meat, poultry, or fish
appeared to have a lower risk of breast cancer than those who
consumed these foods at least once a week (Mills et al., 1989a;
Phillips and Snowdon, 1983). In neither of these studies was this
association statistically significant.
However, a study of 35,000 California
Seventh-Day Adventists, covering a followup period from 1976 to
1982, did indicate an increased risk of colon cancer with
increasing animal fat intake (Morgan et al., 1988). Indeed, those
individuals in the highest third of animal fat intake rates had a
risk of developing colon cancer that was 1.8 times that of
individuals in the lowest third of animal fat intake rates;
people with intermediate animal fat intakes were intermediate in
their risk (Morgan et al., 1988).
In another study of cancer among 25,000
California Seventh-Day Adventists covering 20 years (1960-80),
men who consumed meat at least four times a week experienced a
prostate cancer death rate of 41.9 deaths per 100,000
person-years versus 29.7 deaths per 100,000 person-years for men
who did not consume meat (Phillips and Snowdon, 1983). In the
study begun in 1976, daily consumption of meat was associated
with a risk of developing prostate cancer 1.41 times greater than
that of men who never ate meat (Mills et al., 1989b). In the
earlier study, meat intake was also associated with increased
risk of prostate cancer (Snowdon et al., 1984b).
On the other hand, increased consumption of
beans and lentils appeared to decrease the risk of colon cancer
in the Seventh-Day Adventist population (Morgan et al., 1988). In
fact, among the people who ate the highest amounts of these
foods, the risk of developing colon cancer was one-third that of
people who ate the lowest amounts (Morgan et al., 1988).
Furthermore, consumption of beans and lentils at least three
times per week was associated with approximately 50 percent lower
risk of developing prostate cancer than consumption of beans and
lentils less than once a month (Mills et al., 1989b).
The association of vegetarianism with decreased
risk of certain cancers appears to have correlates with
biological parameters in Seventh-Day Adventists. Vegetarian
Seventh-Day Adventists appear to have less colonic mucosal cell
turnover than nonvegetarians and those at increased risk of colon
cancer (Lipkin et al., 1985). This point is significant, because
it is believed that decreased cell proliferation of the colonic
mucosa may be a hallmark of decreased risk of colon cancer
Macrobiotic diet. No studies to date have
examined directly the role of a macrobiotic diet in chronic
disease prevention. However, a number of studies have examined
associations between macrobiotic diets and biological risk
parameters such as blood pressure, cholesterol levels, and
estrogen metabolism. The earliest of these studies were surveys
of blood pressure and blood lipid levels, which were conducted in
the Boston macrobiotic community. One of these studies showed
that young adults eating a macrobiotic diet had blood pressure
levels of 106 mm Hg systolic and 60 mm Hg diastolic, which was
significantly lower than would be expected in the general
population (Sacks et al., 1974). In fact, in comparison with
people of similar age and sex in Framingham, MA, the subjects'
systolic blood pressure was an average of 11 mm Hg lower and
diastolic blood pressure 14 mm Hg lower (Sacks et al., 1975). In
addition, those in the macrobiotic community who ate some animal
food tended to have higher blood pressures than others in the
macrobiotic community who did not (Sacks et al., 1974).
Blood lipid levels, a general indicator of
coronary heart disease risk, also were substantially lower among
the people eating macrobiotically than in the Framingham
comparison group. In fact, average plasma total cholesterol
levels among the macrobiotic vegetarians was 126 mg/dL versus a
total average plasma cholesterol level of 184 mg/dL in the
age-and sex-matched controls in the Framingham population (Sacks
et al., 1975). Levels of low-density lipoprotein (LDL)
cholesterol--the type of cholesterol that promotes heart
disease--also were substantially lower in those eating a
macrobiotic diet, averaging 73 mg/dL in the macrobiotic
vegetarians and 118 mg/dL in the controls (Sacks et al., 1975).
Although levels of high-density lipoprotein (HDL)
cholesterol--the type of cholesterol that protects against heart
disease--were also lower in the macrobiotic vegetarians (43 mg/dL
vs. 49 mg/dL), the ratio of total to HDL cholesterol, a measure
of the relative atherogenicity (i.e., ability to form plaques) of
the blood lipid profile, was substantially lower among the
macrobiotic vegetarians than in the comparison group (2.9 vs.
3.8). These differences persisted even when adjusted for weight
differences. The relatively favorable blood cholesterol profile
of macrobiotic vegetarians has been confirmed in several other
surveys (Bergan and Brown, 1980; Knuiman and West, 1982; L. Kushi
et al., 1988; Sacks et al., 1985).
In recent years, there has been increasing
interest in the role of fat-soluble antioxidants in
atherogenesis. It has been hypothesized that oxidation of LDL
particles may be a critical step in the uptake of LDL by
macrophages, as well as for some other mechanisms that increase
the atherogenicity of LDL cholesterol (Steinberg and Witztum,
1990). The relative proportion of antioxidants to circulating LDL
has been suggested as an additional measure of the atherogenicity
of blood lipid levels (Berry, 1992). A study of macrobiotic
vegetarians demonstrated that they had not only lower LDL levels
but also higher plasma levels of antioxidants relative to
cholesterol compared to nonvegetarians (Pronczuk et al., 1992).
The favorable cardiovascular disease profile of
macrobiotic vegetarians is likely to be largely due to the
relative avoidance of meat and dairy products. Indeed, when the
diet of macrobiotic vegetarians was supplemented with 250 grams
of beef per day, plasma total cholesterol increased by about 19
percent after 4 weeks, from an average of 140 mg/dL to 166 mg/dL
(Sacks et al., 1981). Comparisons of macrobiotic vegetarians with
lactovegetarians and nonvegetarians also indicate a direct
relationship between average blood total cholesterol levels and
dairy product intake (Sacks et al., 1985).
In the context of cancer risk, studies
comparing women eating a macrobiotic diet with women eating a
typical American diet demonstrate substantial differences in
estrogen metabolism (Goldin et al., 1981, 1982). In fact, women
eating a macrobiotic diet had substantially higher fecal
excretion and lower urinary excretion of estrogens, with somewhat
lower serum levels of estradiol. This point is significant
because many cancers, especially breast cancer, are growth
dependent on hormones such as estrogen. The altered estrogen
metabolism profile of women eating macrobiotically may reflect a
lower risk of breast cancer (Goldin et al., 1981, 1982).
Furthermore, in subsequent studies it was
demonstrated that women eating macrobiotically had dramatically
higher urinary excretion of lignans, such as enterolactone and
enterodiol, and of isoflavonoids, such as daidzein and equol,
than women consuming a lacto-ovo-vegetarian diet or an omnivorous
diet. Women with breast cancer had the lowest levels of these
phytoestrogens (Adlercreutz et al., 1986, 1987). These
differences appeared to be related to greater intake of whole
grains, legumes, and vegetables by the macrobiotic women.
It has been hypothesized that such a fiber-rich
diet may, by the presence of these lignans and other weak
estrogens (i.e., phytoestrogens) in the intestinal tract,
stimulate the synthesis of sex hormone binding globulin in the
liver and may thus decrease levels of free estradiol in the
plasma (Adlercreutz et al., 1987). This may, in turn, reduce the
risk of breast as well as other hormone-dependent cancers. It has
also been suggested that these phytoestrogens (see the
"Herbal Medicine" chapter) may actually compete with
endogenous estradiol on the cellular level, further reducing the
cellular proliferation and, hence, the potentially carcinogenic
effects of estradiol (Price and Fenwick, 1985; Tang and Adams,
In addition to the general macronutrient
differences (lower fat, higher complex carbohydrate intake)
between macrobiotic diets and the standard American diet, certain
foods in the standard macrobiotic diet may have specific
anticancer effects. Examples of such foods, which are absent in
the typical American diet, include various soyfoods, such as miso
and tofu, and sea vegetables (see the "Diets of Other
Cultures" section for a discussion of the health benefits of
Health risks associated with strict vegetarian
diets. Except for vitamin B12 deficiency, diets that exclude meat
or animal products do not produce deficiencies in adults if they
are correctly followed. Nevertheless, there are reports in the
literature that have associated some forms of vegetarianism with
high risks of deficiencies in children and pregnant women (Debry,
1991). The nutrition of children on a vegetarian diet is
considered to be adequate and well balanced when the diet
contains dairy products and eggs. It has been suggested that a
severe or strict vegetarian diet is not suitable for infants or
toddlers. For example, serious deficiency states (e.g., rickets,
osteoporosis, anemia, growth retardation) have been described in
children subsisting on such regimens (Lentze, 1992). However, it
is interesting to note that in a study that examined the
maternity care records of 775 vegan mothers living on a commune
in southern Tennessee, there was only one case of preeclampsia
(Carter et al., 1987). The authors concluded that it is possible
to sustain a normal pregnancy on a vegan diet, and the source of
protein (i.e., animal or vegetable) does not seem to affect birth
weight, as long as vegan mothers receive continuous prenatal
care, supplement their diets with prenatal vitamins, calcium, and
iron, and apply "protein-complementing" nutritional
Diets of other cultures. A cultural diet is
defined as the diet of any group of people who share beliefs and
customs. By this definition, everyone in the United States is a
member of some cultural group. For many cultural groups, food
plays an important role in maintenance of both spiritual and
physical health. The following is a brief overview of several
cultural diets--Asian, Mediterranean, and traditional Native
American Indian--that are thought to provide some protection
against many of the nutritionally related chronic illnesses
prevalent among users of the mainstream diet in the United States
today. Although there are many more cultural diets than are
covered here, solid scientific research has not yet been
collected to establish whether they provide any particular health
Asian diet. This diet is consumed predominantly
by people living in China, Southeast Asia, Korea, and Japan. Rice
is a staple and the center of the meal, and there is little or no
use of dairy products. Soybean products are important sources of
protein and calcium. Dishes incorporate many different
ingredients and may be stir-fried or steamed. This diet, in its
traditional form, is low in fat and high in carbohydrates and
sodium (Kittler and Sucher, 1989).
Mediterranean diet. The Mediterranean Basin is
geographically defined as an inland sea that touches three
continents--Europe, Asia, and Africa--and is surrounded by 15
almost contiguous countries: Spain, France, Italy, the former
Yugoslavia, Albania, Greece, Turkey, Syria, Lebanon, Israel,
Egypt, Libya, Tunisia, Algeria, and Morocco. Divided by language
and, historically, by political and religious conflict, the
Mediterranean countries have for centuries been joined by a
similar diet of daily staples.
The Mediterranean diet consists of a daily
intake of grains, potatoes, pasta, greens and other vegetables,
fruit, beans and other legumes (e.g., lentils, split peas), nuts,
cheese, and yogurt. Fish, poultry, eggs, sweets, and red meat are
eaten less frequently. However, olive oil and garlic are almost
always consumed in abundance (Spiller, 1991). In the case of
Spain, France, and Italy, it is their southernmost parts that are
considered Mediterranean, defined by their use of olive oil.
Another important aspect of the Mediterranean
diet is its emphasis on less refined complex carbohydrates (e.g.,
pasta) in place of sugar and the highly refined starches
generally consumed in the United States, even though direct
evidence for benefit in reducing disease risk is limited.
Anticipated reductions in colon cancer by diets high in grain
fiber diets have been difficult to document epidemiologically,
although inverse associations with vegetables have been seen
repeatedly. However, reduced constipation and reduced risk of
colonic diverticular disease are clear benefits (Willett et al.,
It is interesting to note that in the northern
areas of many of the European Mediterranean countries, where
there is more use of butter, other animal fats, and meat, there
is also a higher incidence of cancer (La Vecchia, 1993).
Traditional Native American Indian diet. Many
foods used throughout the world today were probably first used by
Indians of North, Central, and South America--for example, beans,
corn, cranberries, peanuts, peppers, potatoes, pumpkin, squash,
and tomatoes. Today, Native American Indians live in areas that
are vastly different from one another, so there is no single
typical diet. In fact, traditional diets are prepared
infrequently except for ceremonial occasions. This is true even
for the Arizona Hopi, who still live in old villages that their
ancient ancestors inhabited (Kuhnlein and Calloway, 1977).
Nevertheless, in many American Indian diets, corn is the staple
food. It is eaten fresh roasted or boiled, as hominy, or as
cornmeal in a variety of dishes. Meat is eaten when it can be
obtained by hunting or fishing, but because it is so expensive to
buy, it is used sparingly. Milk and dairy products are not used
often because of a high incidence of lactose intolerance (lactose
is the primary sugar in milk). Berries, wild plants, and roots
are used when available (Robinson and Lawler, 1982).
Research base. The following provides an
overview of research on the effectiveness of some components of
the Asian, Mediterranean, and traditional Native American Indian
diets in lowering some risk factors for disease.
Asian diet. In a cohort study of 265,000 people
in Japan, consumption of miso soup (a food made from soybeans)
appeared to reduce the risk of breast cancer (Hirayama, 1986) and
stomach cancer (Hirayama, 1981). A similar inverse association
was seen between stomach cancer and tofu intake (Hirayama, 1971).
Furthermore, miso has been observed to inhibit formation of
mammary tumors in rodents (Baggott et al., 1990) and may have
antioxidant properties as well (Santiago et al., 1992).
Antioxidant properties have been proposed as a
principal mechanism by which dietary compounds such as
beta-carotene, vitamin E, indoles, and others exert
cancer-preventive effects (Steinmetz and Potter, 1991a, 1991b).
It has also been suggested that sea vegetables, perhaps through
their high concentration of alginic acid, a type of dietary
fiber, may decrease the risk of breast cancer (Teas et al., 1984;
Yamamoto et al., 1987). Beans and bean products, especially those
derived from soybeans (e.g., miso, tofu, tempeh), also contain
protease inhibitors (Messina and Barnes, 1991), isoflavonoids
(Adlercreutz et al., 1987), and other compounds that may play
roles in cancer prevention (Axelson et al., 1984).
Mediterranean diet. The high consumption of
olive oil is considered a major contributor to the
disease-preventive aspects of this diet. Olive oil is a
monounsaturated fat, meaning that somewhere along the fat, or
fatty acid, molecule there is a single site not completely
"saturated" with hydrogen atoms. Substituting
monounsaturated fats, such as olive oil, for saturated fat in the
diet has been shown to reduce LDL cholesterol without affecting
HDL cholesterol, thus providing an improved ratio (Mensink and
Katan, 1992). In addition, monounsaturated fats in the diet have
been found to reduce blood sugar and triglycerides in adult-onset
diabetics (Garg et al., 1992).
In one of the first studies of its kind,
researchers in France placed approximately 300 patients who had
recently had a heart attack (myocardial infarction) on a
Mediterranean type of diet and compared their incidence of having
a second myocardial infarction with that of a control group of
patients who were placed on the standard therapeutic diet. The
experimental group consumed significantly more bread and fruit, a
margarine with a fatty acid composition comparable to that of
olive oil, and significantly less butter, cream, and meat than
the control group. After a followup of about 27 months, there
were only 3 cardiac deaths and 5 nonfatal myocardial infarctions
in the experimental group versus 16 cardiac deaths and 17
nonfatal myocardial infarctions in the control group (de Lorgeril
et al., 1994). It is interesting to note that the patients on the
Mediterranean type of diet had increases in blood levels of
vitamin E and C while controls did not.
Garlic, a staple of the Mediterranean diet,
also has been implicated as a major disease-preventive food. A
growing number of reports in the medical literature suggest that
garlic supplementation may be effective in decreasing serum
cholesterol levels by as much as 15 to 20 percent and thus may
have a protective effect against cardiovascular disease (Kleijnen
et al., 1989; Turner, 1990). Many of these studies have been
faulted for having methodological problems, although a recent
meta-analysis of the various studies reporting a
cholesterol-lowering effect found that garlic did appear to
significantly reduce total serum cholesterol (Silagy and Neil,
There are also reports suggesting that garlic
may prevent the development of cancer in humans (Dorant et al.,
1993). Lin and colleagues (1994) reported that processed garlic
effectively reduced the amount of DNA damage caused by N-nitroso
compounds, which are found in many foods such as cooked meat and
have been implicated as carcinogens (cancer-causing compounds).
Traditional Native American Indian diet. In the
case of the Hopi and Papago tribes, studies have shown that
traditional foods have mineral content superior to federally
provided commodity foods (Calloway et al., 1974). Followers of
traditional Native American diets have found ways of maximizing
available nutrients; an example is in the techniques of
processing the corn used in tortillas, a staple in diets derived
from the Mexican and Central American tradition. The corn is
soaked in lime, which softens the skin of the corn kernels as
well as increasing the calcium content of the resulting tortillas
(Katz, 1987). Traditional lime soaking also liberates bound
niacin in the corn. Because milled corn has been substituted for
lime-soaked corn in Native American Indian diets, niacin
deficiency has become a problem, and incidences of
niacin-deficiency-induced pellagra have increased. Although few
studies have been done on the possible disease-preventive aspects
of the traditional Native American Indian diet, health surveys
have found that heart disease and cancer, two diet-related
diseases, are virtually nonexistent in some Indian populations,
such as the Navajo (Reese, 1972).
This chapter has so far dealt primarily with
basic and clinical research relating to diet and nutrition
interventions either for preventing or treating illness. However,
to discuss such research without mentioning outside factors that
will affect how research results are evaluated or disseminated to
the public provides only a small part of the overall picture.
Because nutritional and dietotherapy interventions affect an
array of biochemical and physiological processes in the body,
evaluating the interventions' effectiveness requires equally
complex methodologies. Also of concern to those who work in this
field is to research and develop "alternatives" to
institutionalized nutrition and feeding programs that directly
contribute to diet-and nutrition-related chronic disease.
Finally, there is the issue of dissemination; no matter how good
the research, it is valuable only if it reaches those who will
benefit from it. Research data should be disseminated not only to
the doctors or other health personnel who may prescribe such
therapies, but also to the eventual target audience (i.e., the
patients). Some of these issues are discussed below.
In most instances, it is virtually impossible
to conduct a double-blind study of a dietary regimen. Patients
obviously will know whether they are being fed a normal diet or a
modified diet. Therefore, a single-blind design (in which the
evaluator of the data is "blind" to who receives which
treatment) is more appropriate for most dietary studies. However,
in some instances a double-blind study is appropriate, such as
when all subjects are given a tasteless, colorless pill. Also,
investigators must consider the possibility of a negative placebo
("nocebo") effect in the control group as well as a
placebo effect in the treatment group. In other words, patients
who think they are not getting the therapy may not get better
because of this knowledge--just as patients who think they are
receiving an effective treatment may get better spontaneously,
independent of the therapy. (See the "Mind-Body
Interventions" chapter for a discussion of placebo and
The recommendation of the recent OTA report
Unconventional Cancer Treatments offers an example of one
possible methodological approach to evaluating many nutritional
interventions. As a practical approach to evaluating the
treatments they had examined, the OTA report's authors proposed a
"best case review" conceptually similar to approaches
used by NCI for evaluating biological response modifiers (BRMs)
(Office of Technology Assessment, 1990). Best case reviews are
discussed in detail in appendix F.
BRMs are agents that exert anticancer effects
in a novel manner. Unlike conventional cytoxic therapy, which
kills tumor cells with slightly less chemical toxicity than
chemotherapy, BRMs stimulate, or potentiate, the body's immune
system to overcome or at least restrain the invading tumor. Most
BRMs currently being investigated are genetically engineered
copies of peptides found naturally in the human body; among them
are tumor necrosis factor, interleukins, and interferons. At an
early stage in this clinical research, NCI researchers recognized
that because BRMs act biologically and not chemically, they had
to be evaluated using a procedure that is significantly different
from the one used for standard cytotoxic agents (Oldham, 1982).
With this in mind, in 1978 NCI created a special Biological
Response Modifiers Program to coordinate research to identify,
study, and clinically evaluate BRMs.
Clinical evaluation of BRMs is difficult
because determining the optimal dose or dosing schedule for the
agent is critically important. Also important is the
identification of responsive tumor types and even of the stage of
disease and metabolic condition of patients who are treated
(Creekmore et al., 1991; Hawkins et al., 1986; Oldham, 1985).
Consequently, experts in BRM research advise against testing BRMs
in large, controlled clinical trials (Phase III trials) until
after these parameters have been optimized in careful individual
tests of the proposed therapy in patients believed to be the most
likely to show a favorable response (Creekmore et al., 1991;
Hawkins et al., 1986; Oldham, 1985). This type of evaluation is
inherently exploratory and observational; therefore, it cannot be
conducted in the same rigidly stipulated way as a Phase III
Because such studies demand the continual
application of good clinical and scientific judgment, they are
demanding of the time and energy of investigators, who typically
are experts keenly interested in the therapy under evaluation.
This time-consuming process is necessary because the consequence
of proceeding prematurely to a Phase III trial is an inconclusive
or falsely negative result. Since dietary and nutritional
interventions often affect biology in ways at least as
complicated as the anticancer BRMs currently being evaluated by
NCI, recommendations concerning the evaluation of BRMs should
apply to the evaluation of many diet and nutrition interventions.
Furthermore, careful scientific judgment is
needed as to when sufficient evaluation has gone on and
confirmation is in order. For example, there is general agreement
in the scientific community that the time is now at hand to
"confirm" the efficacy of megadose antioxidants in the
prevention of coronary artery disease progression in a large
Phase III trial (Steinberg, 1993). This assessment is correct
even though such trials are costly, and there is always a risk of
a false negative result if all the relevant parameters have not
yet been fully optimized. The interaction of a variety of factors
in producing a therapeutic outcome would be expected to be of
particular importance in biological or nutritional therapies
(Christensen, 1993; Weglicki et al., 1993).
An excellent example of the superiority of good
scientific judgment over the premature use of the controlled
clinical trial is the discovery by George C. Cotzias that L-dopa
is an effective treatment for Parkinson's disease (Cotzias et
al., 1967). When Cotzias began his studies, L-dopa was regarded
as an interesting therapeutic idea that had been determined to be
without utility in a series of careful clinical trials that
included controlled double-blind, Phase III methodology (Fehling,
1966; Lasagna, 1972). Had Cotzias not used good scientific
judgment and persistent curiosity by testing L-dopa in careful,
uncontrolled protocols that included larger doses than in the
earlier, methodologically flawed trials, it is entirely possible
that recognition of L-dopa's enormous value would have been
delayed for decades or never recognized at all.
Phase III trials of orthomolecular therapy, for
example, may also require a similarly innovative approach. One
possibility, after preliminary, dose-optimization studies have
been completed, is to randomly allocate suitable patients to
conventional or orthomolecular programs. Much of the evaluation
would have to be "open"; however, symptom-rating scales
could be scored by observers unaware, or "blinded," to
which patients received which treatment.
First and foremost, however, is the requirement
for an openminded approach by intelligent and skeptical clinical
investigators whose effort is respected by their peers. Such
studies also will require good-faith cooperation from academic
medical units and the support provided by adequate research
funding. Evaluation of the research will have to include a
recognition that initially negative results do not prove a
therapy valueless: the therapy may merely have been incorrectly
tested. Investigators should strive to develop hypotheses that
can be objectively tested. Even when testing mechanisms are
novel, they must be rigorous and reproducible by independent
investigators, and their results must be convincing to openminded
but skeptical reviewers. These objectives can and must be
achieved. The cost of not achieving them may be the unnecessary
delay or, worse, the complete dismissal of an effective treatment
for a previously untreatable debilitating illness.
Not even increased openmindedness in mainstream
research or increased Federal funds for research may be enough to
get effective alternative diet and nutrition prophylactic and
therapeutic treatments into more general use. Indeed, without
some significant changes in Americans' beliefs and expectations
about food and nutrition, promising research results--whether
alternative or conventional--will have little impact. For
example, studies indicate that Americans are quite aware of the
relationship between nutrition and health (Cotugna et al., 1992).
However, during the past two decades they have made little
apparent progress toward meeting the RDAs (U.S. Department of
Agriculture and U.S. Department of Health and Human Services,
1990), which recent research indicates may already be too low for
many vitamins and nutrients. Although there has been an increase
in consumption of low-fat milk and a decrease in the consumption
of meat and eggs during the past decade, USDA's 1987-88 national
food consumption survey (U.S. Department of Agriculture, 1988)
indicated that Americans, on average, eat only one serving of
fruit or fruit juice and two servings of vegetables per day. This
amounts to roughly half the recommended Federal Government
minimum (Patterson et al., 1990) and much less than the minimum
advocated by many others. Furthermore, the consumption of
saturated fat by women has consistently remained around 13
percent of total calories (Welsh, 1991).
Numerous Government programs and information
dissemination channels exist that potentially could have a major
positive influence on American dietary habits. Unfortunately,
many, if not most, are having a negative rather than a positive
impact on Americans' dietary knowledge, beliefs, and practices.
These programs and channels include
* Government feeding and food support programs,
* Public education and the mass media,
* School-based and worksite programs, and
* Health care provider settings.
Government feeding and food support programs.
The Food and Nutrition Service of USDA administers 14 food
assistance programs that aim to "provide needy people with
access to a more nutritious diet, to improve the eating habits of
the Nation's children, and to stabilize farm prices through the
distribution of surplus foods" (U.S. Department of
Agriculture, 1993a). More than 25.4 million people participated
in the Food Stamp Program in 1992, and more than 5.6 million
participated in the Special Supplemental Food Program for Women,
Infants, and Children (WIC). In addition, approximately 25
million children participate in the National School Lunch Program
(NSLP) each day, and an average of 900,000 people participate
daily in the Nutrition Program for the Elderly.
Studies have reported that participation in the
Food Stamp Program or the size of the food stamp benefits, or
both, have had a positive impact on the availability of
nutrients. However, the effect of these programs on nutrient
intake is negligible. Only WIC was found to increase intake of
numerous nutrients, including iron, calcium, and vitamin C, among
pregnant women (Rush et al., 1988) and preschool children (Rush
et al., 1988). Moreover, when participants in NSLP were compared
to nonparticipants, increased nutrient intakes of vitamin A,
vitamin B6, calcium, and magnesium (Hanes et al., 1984)--vitamins
typically deficient in the school-aged population (Nelson et al.,
1981)--were observed in the NSLP participant population.
Whether these various feeding programs provide
adequate nutrition for Americans deserves critical analysis. For
example, NSLP has been criticized for maintaining its outdated
purpose of preventing nutritional deficiencies without including
food patterns that would prevent such prevailing chronic diseases
as heart disease, hypertension, cancer, and atherosclerosis
(American School Food Service Association, 1991; Citizens'
Commission, 1990). In light of the findings on the positive
effects of fruits and vegetables (Steinmetz and Potter, 1991a,
1991b) and the negative effects of saturated fats (Willett, 1990)
on health and chronic disease, it may be necessary to modify NSLP
to at least meet the Dietary Guidelines for Americans (U.S.
Department of Agriculture and U.S. Department of Health and Human
In September 1993, assistant secretary of
agriculture Ellen Haas announced plans to improve NSLP by
doubling the amount of fresh fruits and vegetables supplied to
schools and reducing the amount of fat in commodity foods (U.S.
Department of Agriculture, 1993b). This modification is urgently
needed to update NSLP so that it will be in line with the current
scientific findings on diet and disease. Similar modifications
should be made across all USDA feeding and food assistance
programs to help Americans consume a better diet.
Furthermore, for the agricultural system to
meet even the current USDA dietary guidelines, adjustments are
required in the mix and output of farm products. Appropriate new
food policies need to be in place to support such changes. For
example, in the commodity area, the price and income support
programs put a premium on milk fat, and surplus disposal
operations are designed to increase the supply of high-fat butter
and cheese on the market at artificially low prices. This system
runs counter to encouraging better diet and nutrition in the
Public education and role of the mass media.
The primary goal of public nutrition education is to bring about
behavioral changes in individuals', groups', and populations'
dietary patterns presumed to be detrimental to health. The
educational program is designed to provide enough knowledge so
that healthy choices in nutrition can be made. The mass media,
including magazines, newspapers, and television, are a major
source of nutrition information for the public (American Dietetic
Association and International Food Information Council, 1990). An
analysis of mass initiatives in the area of promoting healthy
diet and nutrition choices indicates that such campaigns can be
useful in setting the stage for behavior change (DeJong and
Winsten, 1990). One example is a joint NCI-Kellogg (the cereal
manufacturer) initiative that promoted consumption of a
high-fiber diet through advertising and food labeling on cereal
boxes. On the basis of purchase data from supermarkets in the
Baltimore and Washington, DC, metropolitan area, the purchase of
high-fiber cereals increased 37 percent in the 48 weeks of the
initiative (Levy and Stokes, 1987).
Mass media-based education programs not only
affect the intermediary steps to behavior change but also have
proved to have a more direct influence on health, such as
affecting changes in eating patterns and disease risk factors.
For instance, the Finnish North Karelia Project showed that
education programs using mass media strategies can markedly
reduce certain coronary heart disease risk factors (Vartiainnen
et al., 1991).
In recent years, the social marketing approach,
which draws marketing techniques from the private sector and
focuses on the thorough understanding of consumer needs and
opinions, has been used increasingly in health promotion
campaigns (J. Ling, 1992). This approach can yield promising new
insights into consumer behavior and into product and strategy
design (Walsh et al., 1993), thereby enhancing the efficacy of a
health promotion initiative.
The National Heart, Lung, and Blood Institute's
(NHLBI's) National High Blood Pressure Education Program (NHBPEP)
and National Cholesterol Education Program are examples of
Federal public education programs that extensively use mass media
and social marketing strategies to convey health messages to the
public. Both programs employ the strategy of focusing on raising
knowledge and awareness on two tiers: among the public and among
health care professionals. From NHBPEP's inception in 1972,
awareness, treatment, and control rates for high blood pressure
have increased dramatically (Rocella and Lenfant, 1992), and
age-adjusted stroke mortality has fallen nearly 57 percent
(Rocella and Horan, 1988).
Unfortunately, few nutrition messages in the
mass media promote a healthy diet. Indeed, advertisements for
foods that are high in sodium, fat, or sugar often compete
directly against nutrition messages designed to help people make
better food choices. For example, breakfast cereals, snacks, and
fast foods are among the most heavily advertised products on
television programs aimed at children (Cotugna, 1988), and the
television "diet" consists of foods primarily of low
nutritional value (Story and Faulkner, 1990). Television viewing
also appears to affect food consumption. Studies have reported,
for instance, that the amount of time spent watching television
directly correlates with the request, purchase, and consumption
of foods advertised on television (Clancy-Hepburn et al., 1974;
Gorn and Goldberg, 1982; Taras et al., 1989). Consequently, the
mass media, the food industry, the Government, and health
professionals should collaborate to broadcast health promotion
messages more extensively. One such example is the airing of
public service announcements on Saturday morning children's
television by a major fruit-processing company, which was
prompted by the "Five-a-Day for Better Health" campaign
initiated by NCI and the Produce for Better Health Foundation.
School-based and worksite programs. Schools are
an ideal setting in which to model and encourage healthy
lifestyle behaviors. More than 95 percent of American youth aged
5 to 17 are enrolled in schools (U.S. Department of Education,
1990). School-based nutrition education and physical activity
programs appear to be ideal venues for effecting change in
lifestyle-related risk factors for heart disease, cancer, and
obesity. Children eat one to two meals per day in school, and the
cafeteria can be a learning laboratory where students can
practice and experience positive nutrition habits they learn from
the school curriculum. Previous studies in school-based
cardiovascular research, including the "Know Your Body"
program (Walter et al., 1988), have shown that health promotion
in schools can have a favorable impact on nutrition knowledge and
diet-related skills (Contento et al., 1992) as well as on
specific outcomes, such as blood cholesterol level, carbohydrate
intake, fitness, blood pressure, and smoking status (Stone et
al., 1989). In addition, school-based health promotion programs
have had positive impacts on obesity (Resnicow, 1993).
Additional research of longer duration that
includes multiple components (school food service, curriculum,
family outreach) is needed to determine the degree to which
schools can affect the exercise and diet habits of children.
These studies could be similar to the ongoing NHLBI-funded
"Child and Adolescent Trial for Cardiovascular Health"
and the "Eat Well and Keep Moving" project at the
Tesseract schools in Baltimore, MD.
Worksites are another important channel for
promoting nutrition. Nearly 70 percent of adults between the ages
of 18 and 65 are employed (U.S. Bureau of the Census, 1986). Thus
worksites provide access to large numbers of people and offer the
opportunity to make environmental and social norm changes that
support healthy eating (Sorensen et al., 1986). Indeed, worksite
educational programs have been shown effective in weight control
(Sherman et al., 1989), cardiovascular risk reduction (O'Brien
and Dedmon, 1990), smoking cessation (Windsor and Lowe, 1989),
and cancer screening (Heimendinger et al., 1990). By modifying
cafeteria menus and policy for meals served at corporate
functions to support healthier choices and allowing time at work
for nutrition education activity, worksites can be promising
vehicles in modifying employees' eating habits. However, efforts
should be made to overcome low participation rates and high
dropout rates in worksite programs (American Dietetic
Education of health care providers and patient
counseling. Patients place a great deal of credibility in the
nutrition advice given to them by their physicians (American
Dietetic Association, 1990). Many physicians, however, fail to
provide such advice to their patients. A study by the University
of Minnesota found that only 10 percent of surveyed physicians
gave nutrition advice to more than 80 percent of their patients
(Kottke et al., 1988). Although many physicians view nutrition as
an effective tool that should be used in medical practice, there
are significant barriers that keep physicians from adequately
counseling their patients on issues of diet and nutrition. These
barriers include lack of time, adequate staffs, and insufficient
insurance coverage (Glanz and Gilboy, 1992). In addition,
physicians' perceived inability to effectively alter their
patients' lifestyle practices contributes to this problem
(Wechsler et al., 1983). Another major contributor to physicians
failing to give their patients nutrition counseling may be their
own lack of nutrition knowledge. More than one study of
practicing physicians has found that only about half of those
surveyed felt prepared to provide dietary counseling to their
patients (Kimm et al., 1990).
This lack of adequate nutrition knowledge among
physicians may be partly due to a deficient nutrition curriculum
in U.S. medical schools. In fact, a survey of 45 U.S. medical
schools by the National Academy of Sciences found the state of
nutrition education in medical schools to be largely inadequate
to meet the needs of patients and the medical profession
(National Research Council, 1985). Improved standards for
nutrition education in U.S. medical schools appear to be
necessary if the vast preventive and therapeutic role of
nutrition in health care is to be exploited to the fullest.
In the context of alternative diets or
therapies, an additional barrier to effective counseling by
conventional health care providers is the sometimes outright
hostility toward alternative therapies held by these providers.
For example, surveys have indicated that many cancer patients do
not tell conventional providers that they are pursuing
alternative therapies, in part, because the conventional health
care provider is often unsupportive or skeptical of such
therapies (Eisenberg et al., 1993). In extreme cases, some
conventional providers will refuse to treat a patient whom the
provider knows is seeing an alternative practitioner for the same
condition. Such attitudes are substantial hurdles to overcome for
both the adequate and objective evaluation and dissemination of
effective alternative therapies.
Another problem physicians may encounter when
trying to give nutrition counseling to patients is that American
society is becoming increasingly multicultural. Health
professionals often have difficulty communicating with clients
whose cultural heritage is different from their own. This problem
is particularly acute when a physician is dealing with someone
who comes from a cultural group or society where health and
religion are intertwined (Kittler and Sucher, 1989). For example,
"looking good" is a common goal in many technologically
developed societies, but various cultural groups have a different
view. Mexican Americans, African Americans, and other ethnic
groups do not share the typical American concepts of appropriate
body size, particularly for adult women (Massara, 1980; Schreiber
and Homiak, 1981; Stern et al., 1982). It has been suggested that
the "mainstream" standards for weight in adult women
are, in fact, based more on the value of thinness--which is
related to youth and higher socioeconomic status (Cassidy, 1991;
Sobal, 1991)--than on science or epidemiology (Ritenbaugh, 1982).
Therefore, successful nutritional counseling
depends on culturally sensitive communication strategies; health
care practitioners must be both knowledgeable about general
ethnic, regional, and religious food habits and aware of
individual practices and preferences. Health care professionals
can improve cross-cultural counseling through a four-step process
of self-evaluation, preinterview research, indepth interviewing,
and unbiased data analysis. A detailed description of the
rationale for these steps can be found in Kittler and Sucher
However, the success of cross-cultural
counseling cannot always be measured by a patient's adherence to
a diet. Differences in worldview, traditional food habits, and
factors that influence dietary adaptation may be of greater
consequence to a client than the health implications of the diet.
The best chances of compliance occur when the health care
practitioner is aware of personal cultural assumptions and is
knowledgeable about the cultural heritage of a patient and its
specific influences on the patient's food habits, and when diet
modifications are made with consideration for individual cultural
and personal preferences.
There are some examples of successful
intervention programs that have been based on indepth studies of
the total context of ethnic food consumption. Hall (1987) noted
that materials designed for Mexican-American diabetics not only
had to be translated into Spanish but also had to be redesigned,
incorporating culturally relevant concepts, methods, meal plans,
and activities, to be effective. The same study also found it
advisable to incorporate recommendations for traditional home
remedies that have been shown scientifically to be of value in
the treatment of diabetes. For example, a diabetes intervention
directed toward Mexican Americans may include the use of cooked
prickly pear cactus (nopales), which has long been used in
Mexican folk medicine to control diabetes (Frati-Munari et al.,
1983). Traditional remedies, however, are encouraged only as
complements to biomedical treatments; the Hall program suggests
that prescribed diabetes medications be taken with traditional
herbal teas (Hall, 1987).
Another excellent intervention program is a
physician-based system of dietary risk assessment and
intervention, designed for use with low-literacy, low-income
southern populations (Ammerman et al., 1991, 1992). This program
focuses on the top 20 contributors of saturated fat and
cholesterol that, based on the National Health and Nutrition
Examination Survey II (NHANES II) data, are commonly found in the
diets of African-American populations in the South. Attention is
also given to traditional southern food preparation practices,
such as baking with lard, frying with vegetable shortening, and
seasoning vegetables with meat fat (Ammerman et al., 1991). All
assessment and intervention materials are based on food rather
than on nutrients. Diet change recommendations are linked with
recipes in a southern-style cookbook.
For those who do little cooking at home (a
growing population), information is provided on how to eat
sensibly at fast-food restaurants. Low-cost dietary alternatives
and southern food preferences are emphasized throughout the
materials, which are written at the fifth-to sixth-grade reading
level. The goal of the program is to reduce saturated fat and
cholesterol intake while preserving ethnic eating patterns--that
is, to adapt the traditional diet rather than introduce a radical
transformation of eating patterns (Ammerman et al., 1992).
Evaluation of the program shows promising results, both in the
physicians' administration of the program and in changes in
patients' attitudes. Currently underway is a 5-year, randomized
clinical trial of the effectiveness of the program in lowering
cholesterol among patients in rural Virginia and North Carolina
(Ammerman et al., 1992). In addition, a "northern"
version of this approach and these materials is being tested.
Programs of the type described by Hall and
Ammerman cannot be developed in the absence of the necessary data
specific to the ethnic group being targeted. Multidisciplinary
research with a nutritional-anthropological focus is necessary to
explore these issues further.
It is virtually impossible to list all of the
research opportunities in diet and nutrition that should be
pursued more extensively and vigorously. Rather, this section
presents broad areas where the data indicate that more intense
efforts might yield significant results.
Although there have been many studies to
determine the effect of a single vitamin deficiency, few studies
have attempted to determine the optimal dietary requirement for
most vitamins and minerals. There is increasing evidence that the
consumption of nutrients at RDA levels is not adequate for
promoting optimal health. Thus, nutritional supplementation above
the RDAs for many vitamins and minerals may be indicated. The
following areas of research in vitamin and nutritional
supplementation are likely to yield significant results:
Research is needed to determine how and at what
levels such antioxidants as vitamins E and C and beta-carotene
provide optimal immune enhancement.
* There is growing evidence that some
carotenoids can directly affect cancer cells. Mechanisms may
include free radical and other charged particle quenching, which
would result in less damage to DNA; decreased adenylate cyclase
activity, which would decrease proliferation of the cancer;
generation of regulatory proteins that could alter cell cycles
and metabolism; and other mechanisms as yet unknown (Bendich,
1991). Carotenoids have been shown to protect cells from
mutagens. Further, research into the direct effects of
antioxidants on cancer cells and on DNA repair mechanism is
Research is needed into the role that many
vitamins play aside from being enzyme cofactors. In view of the
interest in free radicals or reactive molecular intermediates in
the pathogenesis of a variety of medical and neurological
diseases, there is a wealth of opportunities for research on the
ability of vitamins and other nutritional supplements to prevent
or reverse the effects of these types of molecules.
Research is needed in the United States to
provide data from controlled studies to verify mostly European
work on the clinical efficacy of minerals such as magnesium and
selenium in the treatment of disease. More extensive intervention
studies are needed to determine whether adding mineral
supplements will improve the preventive effects of other dietary
interventions (e.g., salt and fat restriction) against
cardiovascular disease, and to verify the promising effects from
Europe in prevention of abnormalities in pregnancy. In
particular, the extended study of magnesium treatment of
bronchial asthma is also indicated. There are already many clues
on magnesium's mechanisms of action, and there are many data on
clinical efficacy in a number of clinical diseases or complaints.
It would be more feasible--not to mention less expensive--to set
up double-blind intervention studies supplementing subjects'
existing diets with magnesium or selenium, rather than try to get
them to completely change their diet to include more foods
containing these minerals.
A recent National Institutes of Health (NIH)
report (1994) on calcium recommended that optimal levels of
intake by women to prevent osteoporosis should be 1,500 mg per
day. Because the usual American intake of magnesium is no more
than 300 mg per day, such a level of calcium intake would
constitute a calcium-magnesium ratio of 5:1. It is noteworthy
that in Finland, where the prevalence of osteoporosis is high
(Simonen, 1991), the average calcium-magnesium intake ratio is
4:1, a ratio that has been associated with the highest death rate
in young to middle-aged men from ischemic heart disease in the
world (Karppanen et al., 1978). An NIH consensus development
conference on magnesium, similar to the one held recently on
calcium, would provide a much-needed forum for elucidating other
avenues of research that may be warranted on this important
Studies of Seventh-Day Adventists, macrobiotic
vegetarians, and populations eating Asian and Mediterranean types
of diets indicate that these groups are at lower risk of heart
disease and some cancers. Likewise, studies usually demonstrate
that blood pressure and blood lipid levels fall when participants
follow a vegetarian diet (Cooper et al., 1982; Kestin et al.,
1989; Margetts et al., 1986; Rouse et al., 1986). Prospective
studies of vegetarian groups other than California Seventh-Day
Adventists have found a decreased risk of heart disease and
cancer as well as a decreased risk of death from all causes (Burr
and Butland, 1988; Burr and Sweetnam, 1982; Chang-Claude et al.,
1992; Frentzel-Beyme et al., 1988). Vegetarian populations,
including Seventh-Day Adventists, also appear to be at decreased
risk of other diseases such as gallbladder disease (Pixley et
al., 1985) and diabetes mellitus (Snowdon and Phillips, 1985).
Furthermore, such vegetarian diets as advocated under the
Pritikin program appear to improve control of diabetes (Barnard
et al., 1983).
Accordingly, studies of populations eating
vegetarian and some cultural diets provide evidence that
alternative dietary patterns may have a major impact on disease
risk. Specifically, such studies show evidence of potentially
profound implications for the risk of developing heart disease,
certain cancers (such as colon or prostate cancer), and other
chronic illnesses, such as diabetes. For example, in addition to
containing large amounts of antioxidants, beans, leafy green
vegetables, whole grains, many fruits, and fish are very rich in
magnesium (Seelig, 1980). The Pritikin, Mediterranean,
Seventh-Day Adventist, and macrobiotic diets are, thus, rich in
magnesium. Studies have shown that magnesium supplementation of
animals on atherosclerosis-inducing diets protects against
arterial damage. Animal studies also have shown that magnesium
deficiency increases hypercholesterolemia (especially the LDLs)
and increases vulnerability to oxidative damage (Rayssiguier et
al., 1989, 1993). It has recently been shown that magnesium
repletion and vitamin E are mutually enhancing in protecting
against magnesium deficiency-and stress hormone-induced cardiac
necrosis (Freedman et al., 1990, 1991; Guenther et al., 1992,
1994a; Weglicki et al., 1992), and that vitamin E and magnesium
deficiency shortens the time needed to induce atherosclerosis
(Guenther et al., 1994b).
There is experimental evidence that magnesium
deficiency (at least in very young rodents) can cause leukemias
and lymphomas (Averdunk and Guenther, 1985; Battifora et al.,
1968, 1969; Bois, 1968; Bois and Beaulnes, 1966; Bois et al.,
1969; Hass et al., 1981a, 1981b; Jasmin, 1963; McCreary et al.,
1967), especially when there is also deficiency in such
antioxidants as vitamins C and E, and in selenium
(Aleksandrowicz, 1975). The protective role of magnesium against
certain diseases may be supported by epidemiological findings
about geographic areas low in magnesium where there is a high
prevalence of human and cattle lymphoid neoplasms, leukemias, and
gastric cancers (Aleksandrowicz, 1973; Aleksandrowicz and
Skotnicki, 1982; Seelig, 1979, 1993).
The studies of vegetarian groups and Asian and
Mediterranean populations are congruent with the growing body of
studies in other populations that indicate a potentially profound
role for dietary factors in the etiology of various chronic
illnesses. These include growing evidence of the undesirable
health effects of meat and high-fat dairy intake and the health
promotion effects of abundant consumption of vegetables, fruits,
monounsaturated fats, garlic, and whole cereal grains.
The translation of the findings of these animal
and human studies into therapeutic approaches may alleviate the
burden of some of these diseases. Equally important are measures
that are being taken by industry and the Federal Government to
support healthful dietary habits. Studies need to be undertaken
on a wide variety of alternative diets that have been found to be
* vegetarian diets,
* ultra-low-fat diets,
* high-polyunsaturated-fat diets,
* Mediterranean-type diets, and
* diets rich in soy foods, such as East Asian
Initiatives also are needed along the following
* There is a need for a more critical
examination of dairy products on health, especially regarding
* There is a need for a more critical look at
the effects of meat consumption on health--for example, on
coronary heart disease, colon cancer, and fractures.
* More detailed data are needed on the effects
of fruits, vegetables, monounsaturated fats, and garlic on
cancer, coronary heart disease, cataracts, stroke, and so forth.
* There is a need for more information on the
long-term effects of overrefined carbohydrates (e.g., sugar) on
the human metabolism and immune functioning.
Qualitative research is needed on various
aspects of cultural diets and the effects of cultural beliefs on
health and illnesses. Such studies might include the following:
* Qualitative research on ethnic concepts of
appropriate body shape and size by gender, age, and socioeconomic
* Qualitative research on ethnic definitions of
health and approaches to health.
* Qualitative research on ethnic attitudes and
approaches to dieting.
* Research on how the types of programs
described by Hall and Ammerman can be adapted for use with other
ethnic populations, and evaluation of such programs in meeting
biomedical and nutritional goals (e.g., reduction of cholesterol
The goal in all this research should be to
elucidate categories and concepts of importance to members of the
public and to determine which of their traditions should be
encouraged. These data are critical in achieving the larger
biomedical nutritional goal of a well-nourished and healthy
population by using terms that can be understood by the lay
public, especially members of minorities.
Data that have been accumulating since the
early part of this century indicate that overconsumption of
energy may contribute to chronic illness, while restriction of
energy may promote health and prolong life. Moreschi (1909)
demonstrated that underfeeding could impede the growth of tumors.
Rous (1914) confirmed and expanded those findings, but no further
progress occurred until 1935 when McKay demonstrated a broad
disease preventive effect, as well as extension of lifespan, as a
result of caloric restriction (McKay et al., 1935).
In 1940, Albert Tannenbaum demonstrated that
energy restriction per se in rodents can inhibit tumor initiation
and growth, that increased caloric use stimulated by exogenous
thyroid may inhibit certain cancers and metastases, and that fats
can promote the growth, in many circumstances, of already
initiated tumors (Tannenbaum, 1940, 1942a, 1942b, 1945a, 1945b).
Later, Jose reported that Australian Aborigines who became
malnourished upon weaning, and who regularly developed a
decreased ability to produce antibodies, unexpectedly showed
increased proliferative responses of T lymphocytes upon
stimulation with certain phytomitogens (Jose et al., 1969).
As research progressed, it was demonstrated
that protein-energy restriction could cause in animals the same
enhanced response to phytomitogens seen in Australian Aborigines.
In addition, experiments revealed that even at presumably
dangerously low protein levels (3 to 5 percent), cell-mediated
immunity remained intact and in some cases appeared to be greatly
increased, as in the development of cell-mediated responsiveness
to stimulation with minute doses of antigen. Additional effects
were augmentation of delayed allergic reactions, increased
capacity for lymphoid cells to initiate graft-versus-host
reactions, up-regulated cellular immune responses against
syngeneic and allogeneic tumor cells, and increased capacity to
resist certain types of viral infections (Good et al., 1977,
A direct attempt to follow a high-quality
energy-restricted diet as a health measure has been advocated for
a number of years by R.L. Walford, M.D. at UCLA (Walford and
Crew, 1989). Recently Walford participated in a 2-year experiment
in which he monitored the health of eight humans growing and
recycling all food in the 3.15-acre hermetically sealed
experimental ecological enclosure called Biosphere 2 in Oracle,
AZ. The eight Biosphere 2 subjects underwent 24 months of
moderate caloric restriction (1,700 to 2,400 kcal per day,
despite a heavy work load) with a very high quality
semi-vegetarian diet in rigidly controlled circumstances.
Physiologic changes in the eight volunteers over the 2-year stay
were dramatic, with blood glucose dropping 15 percent,
cholesterol dropping to an average of 125 mg/dL, and blood
pressure dropping to low normal (Walford et al., 1992). Blood
white cell counts also decreased, which, along with the decrease
in glucose, mirrored changes seen in restricted monkeys and
restricted rodents. Further tests are ongoing, but preliminary
results thus suggest that humans respond, at least initially,
much like all other mammals tested on dietary energy restriction.
A great deal more study is needed to see if the immune-enhancing,
life-prolonging effect of an energy-restricted diet in lower
animals also is manifest in humans.
Research shows that physicians can have a
beneficial impact on their patients' lifestyle practices (Inui et
al., 1976; Leon et al., 1987; Russell et al., 1979). For example,
brief antismoking advice given to patients by general
practitioners has been shown to reduce patients' smoking rates by
as much as 7 percent (Russell et al., 1979), which is a
potentially huge public health impact given the prevalence of
smoking. Similar changes in populations' eating patterns, such as
reduction in saturated fat intake, could also have a huge impact
on decreasing the rates of diseases, such as coronary heart
disease and certain cancers, where diet has been implicated in
causation. What is lacking, however, are incisive screening
questions that physicians can use to quickly assess a patient's
nutritional risk within the time constraints of a visit to or by
a physician. Research is necessary into this issue to determine
what screening questions would be both timely and effective in
identifying points of dietary intervention to reduce risk.
Something that became apparent during the
development of this chapter was the wealth of diet and nutrition
information outside the regular electronic databases, such as
MEDLINE. There is a great deal of social science and agriculture
literature relating to diet and nutrition, as well as in the
world literature, that is often overlooked. Furthermore,
literature from before 1965 is not routinely stored in electronic
databases; if it is, abstracts are not included. For example,
dietary modification and the use of vitamins to prevent and
affect disease was the subject of intense research in pre-World
War II Germany (Gerson, 1929, 1935; Sauerbruch and
Herrmannsdorfer, 1928) and, to a lesser extent, in the rest of
Europe (Hval, 1932) and even in the United States (Banyai, 1931;
Emerson, 1929; Mayer and Kugelmass, 1929). However, much of this
information has been lost to many contemporary nutrition
researchers because it is not cataloged in present-day electronic
Much of this older information, as well as
information from such countries as China, India, and Japan, is
university-based clinical research that, if made more widely
available, might be of enormous value to researchers
investigating similar phenomena today. A fruitful research
project could be to screen the older data, the social science and
agricultural data, and the world data that are available in
foreign databases to develop a bibliography of references that
might be added to nationwide databases such as MEDLINE. The World
Health Organization literature, for example, would be a good
starting point in looking for information relating to databases
on diet and nutrition research in other countries.
Attention should be given to examining many of
the widespread popular and folk dietary suggestions for
maintaining health or controlling illness. For example, cranberry
juice has long been known as a folk remedy for controlling or
curing bladder infections in women. Recent analyses of this
popular treatment show that it actually is effective (Walsh,
1992). As noted previously, the prickly pear has long been used
by Mexican Americans as a treatment for diabetes. Biochemical
studies have shown that it does have a mild glucose-lowering
effect, which is due to its content of glucose-6-phosphate
isomerase (Frati-Munari et al., 1983; Ibanez-Camacho and
Roman-Ramos, 1979). Laboratory testing of the efficacy of ethnic
foods used as remedies, as was done with the prickly pear cactus,
might provide interesting results.
Moreover, there are literally hundreds of
popular folk sayings that might warrant serious scrutiny, first
with literature, then with appropriate laboratory and clinical
tests. Some examples are "When people feel weak, they should
eat meat"; "People with lung disorders should avoid
dairy products" (especially common in traditional medical
systems such as Ayurveda); "An apple a day keeps the doctor
Such research should be supplemented by indepth
qualitative research on how and when these remedies are used.
AIDS. AIDS is a chronic disease characterized
by progressive decline in immunocompetence. Because many vitamins
and nutritional supplements are biological response modifiers
that have been shown to stimulate or enhance immune response, the
potential areas of fruitful research in this area are limitless.
There is at least preliminary evidence that
vitamin A or beta-carotene (its precursor) decreases the immune
deficiency that results when animals are exposed to a wide
variety of immunocompromising conditions such as trauma,
infection, irradiation, and treatment with cytotoxic agents
(Seifter et al., 1982, 1983a, 1983b, 1984). There is evidence
suggesting that vitamin A supplementation in immune-compromised
individuals may be necessary to replace a vitamin A deficiency
caused by HIV infection (Lack et al., 1993; Semba et al., 1993).
Many other vitamins and nutritional supplements that have been
shown to affect immune status also may be potentially potent
tools for fighting this deadly infection. This area is ripe for
Cancer. It is well accepted that cancer and its
treatment can cause malnutrition and that malnutrition itself
predicts a poor outcome (DeWys et al., 1980). In general,
however, oral dietary treatments for cancer have not been
evaluated by mainstream medicine for the possible prevention of
malnutrition or for the possible effect on the course of the
disease in cancer patients. There are no nutritional
recommendations per se for the cancer patient in mainstream
oncology (Office of Technology Assessment, 1990), and no diet is
currently recommended publicly by NCI or the American Cancer
Society for use in cancer treatment. Those nutritional support
measures that are offered usually come only after patients have
reached advanced stages of cancer and have become malnourished,
often as a result of side effects of their treatment (e.g.,
chemotherapy) (American College of Physicians, 1989; Shike and
Little is understood about the nutritional
requirements of cancers. However, there is growing evidence that
many types of tumors have an increased need for iron in order to
grow (Elliott et al., 1993; Weinberg, 1992). Red meat is one of
the best sources of iron, and iron from red meat continues to be
absorbed even if body stores of iron are plentiful (Ascherio and
Willett, 1994). Therefore, there is at least a theoretical basis
for proposing that cancer patients eat a primarily vegetarian
diet to slow the growth of their tumors. Furthermore, although
the epidemiological data provide solid support for
recommendations to consume an abundance of vegetables and fruits
or vitamin supplements to prevent cancer, there is a need for
research on the effects of such nutritional interventions on
individuals who already have cancer. Immunological parameters
such as certain immune cell activity or levels of certain
cytokines (immune-cell-activating compounds) would provide
information about whether such diets do or do not increase the
body's ability to attack cancer cells.
The 1990 OTA report Unconventional Cancer
Treatments suggested that at least certain aspects of most of the
unconventional dietary regimens for cancer it reviewed (e.g.,
intake of fresh fruits and vegetables and reduction or
elimination of sodium and fat) are consistent with current
Federal dietary recommendations about reducing the risk of
contracting certain types of cancer and other illnesses (Office
of Technology Assessment, 1990). The controversial aspects of
these therapies, according to OTA, is the idea that dietary
treatment can cause the regression of cancer. It is possible that
the earlier such dietary regimens are begun, the more effective
they are. It would be informative to look at various aspects of
some of these regimens to determine whether they conform to basic
biochemical and immunological research relating micronutrient
manipulation to improving immune function or the inhibition of
cancer cell growth. For example, Simone (1983) suggested that
coffee enemas may increase absorption of vitamin A. There is
evidence that vitamin A may play a vital role in boosting immune
function (see the section on orthomolecular medicine in this
chapter). The Gerson diet is estimated to provide approximately
100,000 IU of vitamin A daily (Seifter, 1988). Further studies
are needed to confirm the ability of such measures to increase
the absorption of micronutrients.
Heart disease and diabetes. Studies such as
those using fat-restricted or fat-modified diets (i.e., intake of
greater amounts of monounsaturated fats) have produced quite
credible evidence suggesting not only that cardiovascular disease
may be stabilized through such methods, but also that death rates
from cardiovascular disease can be greatly reduced. Dietary
intervention for coronary heart disease may find broader
application if attempts are made to further both clinical
research and use. A systematic review of the literature, broader
clinical evaluations, and the development of clinical guidelines
could lead to general acceptance. Efforts to disseminate
information and transfer technology may be essential. Cost
comparisons with conventional treatments may be instructive.
The following are specific areas that are
likely to yield fruitful results:
* Sufficient evidence now exists to compel
larger scale, multicenter, randomized clinical trials of modified
diets such as the Ornish regimen, the Mediterranean-type diet,
and high-soy-content diets.
* Dean Ornish's program relies heavily on
relaxation techniques as well as fat restriction. It would be
informative to know which aspect of his regimen contributes most
to the regression of heart disease. If the relaxation component
turns out to be a significant factor, this knowledge could
potentially save the overall health care system billions of
* The Pritikin diet and other diets that
require low fat, low cholesterol, high fiber, and high complex
carbohydrate consumption should be tested and evaluated (in terms
of all their components) for the treatment of adult-onset
diabetes. Even if a small percentage of the nation's 11 million
diabetics could control their disease with diet, the savings--in
health improvement, delayed mortality, and financial costs--would
Food allergies. Despite the large body of
literature on food allergies, there is still a need to further
study the approach taken by environmental medicine in a variety
of other conditions commonly encountered. A mechanism similar to
that proposed for arthritis has been proposed in asthma,
ulcerative colitis, migraines, hyperactivity, recurrent
infections, and other common conditions. The testing techniques
need further validation, as does treatment with immunotherapy,
environmental control units, and basic biochemical understanding
of the causes of chemical hypersensitivity and other "20th
More work needs to be done in the area of food
intolerance and neuropsychiatric disorders. Egger and colleagues
(1992) have recently implicated an immune system effect as being
the mechanism by which incriminated foods produce hyperactivity.
Work from other investigators is sorely needed.
This chapter has demonstrated that the more we
learn about the potential influences of dietary factors on
health, the more we must realize the need for maintaining an open
mind. There are numerous examples where medical consensus--even
when it represents the honest opinions of the most knowledgeable,
leading scientists in the field--has clearly been wrong. For
example, not long ago, the medical community strongly advised
pregnant women to avoid taking vitamin supplements. Today
pregnant women are advised to do exactly the opposite, especially
with regard to taking folic acid to prevent neural tube defects.
Another widespread erroneous consensus medical recommendation was
the use of margarine rather than butter to reduce risk of
coronary heart disease. It now seems, that at least some
margarines, which are made from partially hydrogenated vegetable
oils, are no better, if not worse, than butter in reducing the
risk of heart disease.
Each of these cases was based on limited or no
direct evidence. Further, many of the most promising research
topics of today, such as the role of dietary antioxidants or
alternative dietary lifestyles in preventing coronary heart
disease and specific cancers, were topics dismissed by most
nutritionists only a few years ago as practices of misguided
vitamin and food faddists. Given the extreme complexities of the
interrelationships between diet and human health and the
relatively meager directly relevant data, an element of humility
is appropriate in evaluating "alternative" dietary
practices. Lack of data, such as from randomized trials, should
not be confused with evidence of no benefit. However, a
willingness to consider possible benefits of alternative diets
does not imply blind acceptance of them, but rather should foster
a rigorous scientific evaluation of potentially beneficial
Unfortunately, nutritional therapies or dietary
practices that do not readily fit into the "norm"
previously have too often been routinely dismissed without such a
rigorous examination. An ample investigation of a diet or
nutritional intervention should test it in an appropriate model,
under the appropriate conditions, and using appropriate research
methodologies. In particular, potential study subjects must be
selected with extreme care; that is, they should be individuals
in which the dietary or nutritional modification, if truly
beneficial, is likely to produce an effect. Moreover, if a study
involves a micronutrient or vitamin or mineral supplementation,
the dosage must be optimized to ensure that the intervention will
have the opportunity to display an effect. Also, any evaluation
of an alternative diet or nutrition research experiment will have
to include a recognition that initially negative results do not
prove any therapy is valueless; rather, the therapy may merely
have been incorrectly tested. Thus, going the extra step is an
imperative in conducting this type of research.
Finally, more efforts are needed in translating
findings related to specific micro-and macronutrients to whole
foods and practical, attractive diets. Only by doing this can
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antioxidant: A compound that prevents oxidation
of substances, particularly lipids, in food or in the body.
Antioxidants are especially important in preventing the oxidation
of polyunsaturated lipids in the membranes of cells. An
antioxidant is able to donate electrons to electron-seeking
compounds such as free radicals (see below). This in turn reduces
electron capture and, thus, breakdown of unsaturated fatty acids
and other cell components by oxidizing agents.
atherosclerosis: A buildup of fatty material in
the arteries, including those in the heart.
carbohydrate: A compound containing carbon,
hydrogen, and oxygen atoms; most are known as sugars, starches,
and dietary fiber.
diet: All of the foods a person consumes either
on a daily basis or on average over a period of time.
enzyme: A compound, usually a protein, that
speeds the rate of a chemical reaction but is not altered by the
epidemiology: The study of the occurrence,
cause, and prevention of disease and death in human populations.
fatty acid: A principal component of fats and
oils. A fatty acid is composed of a chain of carbon and hydrogen
atoms with an acid group at one end. Examples include stearic
acid (a saturated fatty acid), oleic acid (a monounsaturated
fatty acid), and linoleic acid (a polyunsaturated fatty acid).
free radical: Short-lived form of compounds
with an unpaired electron in the outer electron shell. Because
free radicals have an electron-seeking nature, they can be very
destructive to electron-dense areas of cells, such as DNA and
lipid: A compound containing an abundance of
carbon and hydrogen, little oxygen, and sometimes other atoms.
Lipids include fats, oils, and cholesterol.
lipoprotein: A compound found in the
bloodstream containing a core of lipids with a shell of protein,
phospholipid, and cholesterol.
macronutrients: Compounds, such as fats,
proteins, and carbohydrates, that must be broken down or
metabolized by the body to obtain energy or basic building
micronutrients: Minerals and vitamins that are
required for proper functioning of the body. These often act as
cofactors or coenzymes in enzymatic processes.
myocardial infarction: Death of part of the
heart muscle due to a heart attack.
nutrients: Chemical substances in food that
nourish the body by providing energy, building materials, and
factors to regulate needed chemical reactions in the body.
nutrition: The biological science of nutrition
includes the processes by which the organism ingests, digests,
absorbs, transports, metabolizes, and excretes food substances.
Nutrition as a science and discipline also includes areas such as
food policy, dietary behaviors, agricultural practices, cultural
and anthropological aspects of food, etc.
prospective studies: Studies in which subjects
are enrolled prior to their having developed the endpoint (i.e.,
condition or disease) of interest, and they are often followed
until they develop such endpoints. Examples of prospective
studies include clinical trials, in which some study subjects are
given an investigator-imposed intervention, and cohort or panel
studies, which usually do not include investigator-imposed
retrospective studies: Studies undertaken to determine whether those with and without a particular disease or condition differ according to past exposures. Examples of such studies include case-control studies and retrospective cohort studies.
The mainstream, or "standard,"
American diet, which is one of the world's most affluent diets,
is derived primarily from the traditions of the British and
German cultures. The British tradition emphasizes meat and bread.
These staples traditionally form the core of the meal, with
vegetables serving as side dishes and fruits either eaten as
snacks between meals or mixed with wheat, milk, and eggs to form
a sweet pudding, pie, or cake, which is called a
"dessert" (Kittler and Sucher, 1989).
The German tradition emphasizes dairy foods, especially milk and cheese (Kittler and Sucher, 1989). Pork is a staple for Germans and is the second most important red meat for Americans, who like it in every form from roast to "lunchmeat" (cold cuts) to sausages and bacon. Two core American meat-and-grain foods are actually of German origin: hamburgers and frankfurters (or wieners) (Yoder, 1981).
Margarine starts out as a liquid vegetable oil.
However, it is converted to a form that will remain solid at room
temperature, and thus resemble butter in texture, by a process
called hydrogenation. The hydrogenation of vegetable oils changes
the three dimensional structure of the fatty acids that make up
the oil, converting the naturally occurring cis fatty acids to
trans fatty acids. Oils composed primarily of hydrogenated fats
typically "melt" at higher temperatures than those
composed of nonhydrogenated (polyunsaturated) fats.
Over the past few decades many American
physicians and nutrition experts have advised people to eat
margarine in place of butter and lard, which contain
"saturated" animal fats and are associated with an
increased risk of developing coronary heart disease (CHD).
However, recent evidence suggests that consuming significant
amounts of margarine may pose health risks of its own, unrelated
to problems caused by saturated animal fats. This is because
trans fatty acids have been found to increase blood levels of
low-density lipoprotein cholesterol, which is associated with an
increased risk of developing CHD. At the same time, trans fatty
acids also lower blood levels of high-density lipoprotein
cholesterol, which has a protective effect against CHD. In
addition, recent epidemiological studies have found a positive
association between the consumption of trans fatty acids and CHD.
Thus, it now appears that consuming margarine may not offer any
health advantages over consuming butter (Willett and Ascherio,
In fact, because the average American takes in approximately 4-7 grams of these trans fatty acids daily by eating margarine and processed foods containing partially hydrogenated vegetable oils, the number of excess deaths in the United States attributed to the consumption of such food products is likely to be substantial.
Figure 1. Food and Nutrition Board, National
Academy of Sciences-National Research Council Recommended Dietary
Allowances,a Revised 1989
Designed for the maintenance of good nutrition
of practically all healthy people in the United States
Fat-Soluble Vitamins Water-Soluble Vitamins Minerals
Vita- Vita- Vita- Vita- Vita- Thia- Ribo- Vita- Fo- Vita- Cal- Phos- Mag- Sele-
Age (years) Weightb Heightb Protein min A min D min E min K min C min flavin Niacin min B6 late min B12 cium phorus nesium Iron Zinc Iodine nium
Category or Condition (kg) (lb) (cm) (in) (g) (:g) RE)c (:g)d (mg "-TE)e (:g) (mg) (mg) (mg) (mg NE)f (mg) (:g) (:g) (mg) (mg) (mg) (mg) (mg) (:g) (:g)
Infants 0.0-.5 6 13 60 24 13 375 7.5 3 5 30 0.3 0.4 5 0.3 25 0.3 400 300 40 6 5 40 10
0.5-.0 9 20 71 28 14 375 10 4 10 35 0.4 0.5 6 0.6 35 0.5 600 500 60 10 5 50 15
Children 1-3 13 29 90 35 16 400 10 6 15 40 0.7 0.8 9 1.0 50 0.7 800 800 80 10 10 70 20
4-6 20 44 112 44 24 500 10 7 20 45 0.9 1.1 12 1.1 75 1.0 800 800 120 10 10 90 20
7-10 28 62 132 52 28 700 10 7 30 45 1.0 1.2 13 1.4 100 1.4 800 800 170 10 10 120 30
Males 11-14 45 99 157 62 45 1,000 10 10 45 50 1.3 1.5 17 1.7 150 2.0 1,200 1,200 270 12 15 150 40
15-18 66 145 176 69 59 1,000 10 10 65 60 1.5 1.8 20 2.0 200 2.0 1,200 1,200 400 12 15 150 50
19-24 72 160 177 70 58 1,000 10 10 70 60 1.5 1.7 19 2.0 200 2.0 1,200 1,200 350 10 15 150 70
25-50 79 174 176 70 63 1,000 5 10 80 60 1.5 1.7 19 2.0 200 2.0 800 800 350 10 15 150 70
51+ 77 170 173 68 63 1,000 5 10 80 60 1.2 1.4 15 2.0 200 2.0 800 800 350 10 15 150 70
Females 11-14 46 101 157 62 46 800 10 8 45 50 1.1 1.3 15 1.4 150 2.0 1,200 1,200 280 15 12 150 45
15-18 55 120 163 64 44 800 10 8 55 60 1.1 1.3 15 1.5 180 2.0 1,200 1,200 300 15 12 150 50
19-24 58 128 164 65 46 800 10 8 60 60 1.1 1.3 15 1.6 180 2.0 1,200 1,200 280 15 12 150 55
25-50 63 138 163 64 50 800 5 8 65 60 1.1 1.3 15 1.6 180 2.0 800 800 280 15 12 150 55
51+ 65 143 160 63 50 800 5 8 65 60 1.0 1.2 13 1.6 180 2.0 800 800 280 10 12 150 55
Pregnant 60 800 10 10 65 70 1.5 1.6 17 2.2 400 2.2 1,200 1,200 320 30 15 175 65
Lactating 1st 6 months 65 1,300 10 12 65 95 1.6 1.8 20 2.1 280 2.6 1,200 1,200 355 15 19 200 75
2nd 6 months 62 1,200 10 11 65 90 1.6 1.7 20 2.1 260 2.6 1,200 1,200 340 15 16 200 75
aThe allowances, expressed as average daily
intakes over time, are intended to provide for individual
variations among most normal persons as they live in the United
States under usual environmental stresses. Diets should be based
on a variety of common foods in order to provide other nutrients
for which human requirements have been less well defined. See
text for detailed discussion of allowances and of nutrients not
bWeights and heights of Reference Adults are
actual medians for the U.S. population of the designated age, as
reported by NHANES II. The median weights and heights of those
under 19 years of age were taken from Hamill et al. (1979) (see
pages 16-17). The use of these figures does not imply that the
height�to�weight ratios are ideal.
cRetinol equivalents. 1 retinol equivalent = 1
:g retinol or 6 :g $�carotene. See text for calculation of
vitamin A activity of diets as retinol equivalents.
dAs cholecalciferol. 10 :g cholecalciferol =
400 IU of vitamin D.
e"�Tocopherol equivalents. 1 mg d�"
tocopherol = 1 "�TE. See text for variation in allowances
and calculation of vitamin E activity of the diet as
f1 NE (niacin equivalent) is equal to 1 mg of
niacin or 60 mg of dietary tryptophan.