In February, the New York Academy of Sciences sponsored an important
conference entitled, "Beyond Deficiency: New views on the function
and health effects of vitamins." The multidisciplinary conference
was indeed a watershed in the perspective of the "establishment"
on the role of vitamins in health. This conference was the impetus for the
TIME, U.S. News & World Report and several syndicated New
York Times articles.
"This Conference (brought) together the considerable evidence that
vitamins have biochemical and nutritional functions far beyond their historical role as coenzymes or for the prevention of deficiency symptoms...The formidable amounts of epidemiological and other data indicating that risk of diseases
such as cancer, cardiovascular disease, cataracts, and Parkinson's disease
can be influenced by vitamins (were) explored."
Dr. Lawrence J. Machlin, a world renowned vitamin E researcher and the Director
of the Department of Clinical Nutrition of Hoffmann-La Roche, co-chaired
the conference, along with Dr. Howerde E. Sauberlich of the University of
Alabama at Birmingham. I had the chance to chat with Dr. Machlin after the
conference, and I would like to share the conversation with you.
Dr. Machlin is widely recognized as the World's leading authority on the
science of vitamin E, having published more than 125 scientific papers on
vitamin E, edited 6 books and chairing or co-chairing 5 conferences on vitamins.
Dr. Machlin is the Director of the Department of Clinical Nutrition of Hoffman-La
Roche and is an Adjunct Professor of Nutrition at Cornell University Medical
College. He has also taught nutrition at Washington University and New York
University. His latest book is "Handbook of Vitamins, 2nd Ed.
Passwater: Dr. Machlin, congratulations on Co-chairing the
recent conference "Beyond Deficiency: New Views on the function and
health effects of vitamins." Do you believe that the conference helped
mainstream nutritionists see the benefits of vitamins on health beyond the
concepts of the classical deficiency considerations?
Machlin: Yes, I definitely think the conference accomplished
that by doing two things. We had extremely credible scientists making presentations
both on the health benefits of vitamins, and just as important, we had scientists
address the issue of the mechanisms by which vitamins work, thereby providing
a biochemical explanation for why vitamins may have health effects beyond
merely preventing deficiencies. As one example, the conference brought together
and reviewed the latest information on the antioxidant function of vitamins
in reducing the risk of heart disease and cancer. Another example was the
research showing that vitamin B-6 has a function additional to its "classical"
role as a coenzyme. Dr. James Leklem of Oregon State University pointed
out that vitamin B-6 also has a role regulating hormone metabolism and in
that role, higher amounts than the current RDA may be needed.
Passwater: Will the new recognition of the roles of vitamins
beyond their classical roles reach a significant number of health scientists
Machlin: A large percentage of the audience were already at
least partial believers, but I'm hoping that when the proceedings will be
published by the end of the year, the information will be accessible to
a larger segment throughout the nutritional community and other fields as
well. (Note: The TIME magazine and New York Times syndicate articles appeared
after this conversation.)
Passwater: I saw a possible coming together of the minds of
lipidologists and vitaminologists in the understanding of the causes of
heart disease. Particularly, I have in mind the presentation by Dr. Ishwarlal
Jialal of the University of Texas Southwestern Medical Center in Dallas
discussing the importance of the antioxidant nutrients in preventing oxidation
of low-density lipoprotein and how this lowers heart disease risk. He made
an excellent case for low-density lipoprotein protection, but I feel that
an equally valid case can be made for protecting high-density lipoproteins.
What do you see from your point of view?
Machlin: For years practically all of the research on atherosclerosis
has focussed on dietary fat as the main nutritional risk factor for cardiovascular
diseases and this focus has probably slowed scientific progress. At this
conference, there were at least two areas which were new. Previously, the
main hypothesis was that LDL is the "bad" form of cholesterol
circulating in the blood and leading to atherosclerosis. Now the thinking
is that it is not "bad" or injurious unless it becomes oxidized
-- by a process similar to how fat turns rancid. Therefore just as an antioxidant
protects fat from going rancid -- vitamin E, beta-carotene, and vitamin
C potentially protect LDL from oxidation, and therefore, prevent atherosclerosis
(the beginning stage of cardiovascular disease). Dr. Jialal previously presented
data that vitamin C was effective in in vitro tests , and presented
evidence that in human subjects, vitamin E prevented LDL oxidation. His
work with vitamin E confirms other research that vitamin E supplements prevent
Another important story relates to homocysteine, an unusual amino acid,
thought to provoke atherosclerosis by injuring blood vessels. Dr. Joel Mason
of the USDA Human Nutrition Research Center on Aging at Tufts University
reviewed data showing that vitamin B-12, folate and vitamin B-6 all seem
to influence the level of homocysteine in the blood. That is, the higher
the amount of these B-vitamins -- particularly folate, the lower the amount
of homocysteine in the blood, and therefore, the lower the risk of cardiovascular
disease. Others have shown that this factor is an "independent"
risk factor, that is, an additional factor to all of the lipid (blood fat)
factors. This has important implications for future research.
Passwater: I sense increased progression from animal laboratory
research into epidemiology. As an example, Dr. Gladys Block of the University
of California at Berkeley has been very successful in presenting a lot of
the information on the strength of the various epidemiological studies on
vitamin C, into various journals, and she gave an excellent review at the
conference. Could you comment on the results that the epidemiologists are
now reporting and what effect this might have on the dogma of the classical
nutritionist who have looked only at deficiencies and normal growth? How
about the RDA? Will Clinical Researchers see a need to conduct clinical
Machlin: I can give you a personal history. I spent most of
my career doing studies with animals and I looked with considerable skepticism
on epidemiological studies. But, in the last ten-to-fifteen years, my opinion
has turned around. I now feel that the field of epidemiology is absolutely
essential for giving us guidance in nutrition. It has occurred to me that
nutritionists are already making extensive use of epidemiology.
For example, the recommendation for lower dietary saturated fat and cholesterol
is based almost entirely on epidemiology. It has only been in the last six
or seven years that intervention trials (with cholesterol-lowering drugs)
were shown to lower the risk of cardiovascular disease.
With vitamins, as you indicated earlier, there is a tremendous amount of
information about vitamins lowering the risk of cancer and cardiovascular
disease. In some cases, I think it's going to be almost impossible to get
the unequivocal data that is obtainable only by long-term preventative intervention
trials. One reason is that such trials would have to be quite massive and
extremely expensive. The only agency that could afford it would be the U.
S. Government and there are only going to be a limited number of these trials
that can be funded.
The other reason is that in the case of chronic diseases that develop over
decades, it is extremely difficult to conduct an intervention trial that
lasts ten years or more. However, since these trials do produce the least
equivocal data, we should try to do as many as possible.
Passwater: Do you feel that the publications of the epidemiologists
-- for example, Dr. Block's on vitamin C -- will have an effect on the future
of RDA committees, where in the past, they have been trying to lower the
RDA for vitamin C? Do you think that this will at least halt that trend,
if not move the committee towards looking beyond deficiency?
Machlin: I'm hoping that it will have some impact. If epidemiologists
establish that a group of people getting 200 milligrams or more of vitamin
C have lower risk of cancer and heart disease, that certainly gives an impetuous
to at least increase the RDA to above what it is today.
One issue is the consistency of the epidemiology. For example, over 90%
of published studies show that higher intakes of beta carotene lowers the
risk of certain cancers. If in addition you have a base in biochemical studies
and animal studies, this increases the believability of the epidemiology.
In other words, if you have a biochemical basis, animal studies that demonstrate
that a vitamin has an effect , and in addition to that you have a large
number of epidemiological observations, then I think there is a strong case
to make some recommendations..
Passwater: That is precisely my feeling, but I have felt that
in reading many of the studies of epidemiologists, that they are not aware
of the -- or they are choosing to ignore -- the laboratory animal research
that has been around for a number of years. As an example, the debate over
whether or not it's beta-carotene per se, or other components of fruits
and vegetables, when these people are arguing the case that their studies
are showing that yes, we looked at the consumption of fruits and vegetables,
and we calculate the beta-carotene content, they don't seem to ever want
to refer to the literature from laboratory animal studies that shows that
beta carotene itself -- in isolation -- can have a dose-dependent relationship.
Is it just my sensitivity or what?
Machlin: I think you are absolutely right. Part of the problem
is epidemiologists do the epidemiological studies, and they are not by training,
nutritionists. So they often simply don't have that historical nutritional
perspective. Fortunately, there are more and more groups, such as the Harvard
group headed by Dr. Walter Willet, specifically oriented towards nutrition.
Those groups tend to make much more of an effort to review the biochemistry
and animal data make the link with the epidemiological studies. Hopefully,
that trend will continue. Ideally, the epidemiologists and the nutritional
biochemists will work as a team.
Passwater: Yes, and your conference should get the two disciplines
talking to each other more and more. But, let's consider some old, less
sophisticated research for a moment. You and I have previously discussed
the results of my 1974-6 epidemiological study of vitamin E and heart disease.
Even though that study may have been limited to a "self-selected"
population, I felt that the numbers were so strong that there had to be
a link. Later, we learned that one explanation might be that vitamin E prevented
heart attacks by reducing platelet aggregation which affects the tendency
for blood to clot. And more recently, we have learned of other functions
of vitamin E that help explain how vitamin E can prevent heart disease.
But, back in 1975, did you believe that vitamin E was protective against
Machlin: I wasn't completely convinced at that time, but I
thought that there was that possibility. We were still living under the
shadow of the reports of the Shute brothers that were derided by most of
the medical community. So this was a field that had to be approached quite
cautiously. In the interim between 1975 and now, a lot of things have happened.
We have many more animal studies, some showing that vitamin E is very important
in preventing ischemia reperfusion injury. This is a cellular injury caused
by free radicals that are released when the blood flow is returned to an
organ when the blood has been cut off for a time. There is a huge literature
now showing that vitamin E administered before the blood is cut off, considerably
reduces the damage. In addition, there have been a couple of studies
published showing a direct effect of vitamin E preventing atherosclerosis
in laboratory animals. There are now a number of studies showing vitamin
E reduces the arrhythmia (irregular heart beats) produced in laboratory
The whole LDL-oxidation theory has emerged. Vitamin E is the major antioxidant
in LDL. You mentioned the relationship of vitamin E to blood platelet function.
There is some epidemiology showing that populations consuming more vitamin
E have lower incidences of heart disease and your own studies suggest
that mortality is reduced in people taking vitamin E supplements for lOng
periods of time. Fortunately, I think that there will be some largescale
intervention studies in the next decade which should yield useful data on
this issue.Passwater: Last August, the National Institute of Blood, Lung
and Heart Disease called about 30 researchers together to consider whether
or not there is adequate data to warrant a largescale, longterm trial of
antioxidant vitamins in the prevention of heart disease. Would you comment
on this possibility and other clinical studies that are under way?
Machlin: Experts were summoned to decide how they could test the premise
that antioxidants may reduce the risk of heart disease. There was some agreement
that antioxidant vitamins would be preferred to drugs for this study. Vitamins
are safe whereas drugs have risks. The Harvard Physicians' study with 29,000
subjects is already underway and should yield useful information on betacarotene.
Another study evaluating vitamin E and betacarotene in 45,000 women
will start this year.
Passwater: The data from the Californian residents who participated in my
1974 vitamin E study were used by Linus Pauling, Ph. D. and epidemiologist
Jim Enstrom, Ph.D. to study the role of vitamins and health in California.
Initially, at least, they found a beneficial effect. However, that
study, which was published in the Proceedings of the National Academy of
Science, was used by someone to suggest that vitamin E at an intake of 1,000
IU daily was detrimental to health. I know that you replied to that silly
notion with a letter to the editor of a scientific journaL to correct that
misrepresentation of the data.
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to © Richard A. Passwater, Ph.D. and Whole Foods magazine (WFC Inc.).