Life Extension Magazine August 2000
A Critical Analysis of The National Academy of Sciences' Attack on Dietary Supplements
What They Said About Vitamin E?
Compared to the paucity of data reported about selenium, the authors provide an extensive section of excerpts from the published literature about the benefits of vitamin E. Beginning on pages 211-212 of the book, the authors reveal the molecular basis by which vitamin E may protect against heart attack and stroke as follows:
"Vitamin E does inhibit LDL oxidation whether induced by cells in culture or by copper ion in vitro. In addition, vitamin E could affect atherogenesis at a number of steps, based on the following in vitro observations:
- Vitamin E inhibits smooth muscle cell proliferation through inhibition of protein kinase C.
- Vitamin E inhibits platelet adhesion, aggregation, and platelet release reactions.
- Vitamin E inhibits plasma generation of thrombin, a potent endogenous hormone that binds to platelet receptors and induces aggregation.
- Vitamin E decreases monocyte adhesion to the endothelium by down-regulating expression of adhesion molecules and decreasing monocyte superoxide production.
- Vitamin E potentiates synthesis of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation.
- Vitamin E mediates upregulation of the expression of cytosolic phospholipase A2 and cyclooxygenase.
- Vitamin E enrichment of endothelial cells in culture inhibits the expression of intracellular cell adhesion molecule and vascular cell adhesion molecule induced by exposure to oxidized LDL cholesterol."
In animal models, the authors conclude that the “antioxidant hypothesis of atherosclerosis is strongly supported.”
In a summary of human epidemiological studies, the authors cite “risk reductions of 30% to 60% in the highest, relative to the lowest, quintile of intake (of vitamin E) in these studies.” The authors then cite interventional human studies where vitamin E showed a risk reduction benefit or no risk reduction benefit. Since some studies showed no risk reduction, the conclusion was to not recommend vitamin E supplementation for the prevention of cardiovascular disease.
When looking at diabetes mellitus (Type I or Juvenile diabetes), the authors related the results of many studies indicating that vitamin E might protect against the complications associated with diabetes including excessive oxidative stress, platelet hyperactivity and neuropathy. They also reported that vitamin E may allow better control of blood glucose. The author’s conclusions about whether diabetics should actually use vitamin E were stated page 218 of the 512-page book as follows:
"The available data strongly suggests that individuals with diabetes are subject to increased oxidative stress. However, no clinical intervention trials have tested directly whether vitamin E can ameliorate the complications of diabetes mellitus. . . . Studies on humans show that lipid and lipoprotein oxidation proceed more rapidly in patients with diabetes than in nondiabetic people and that treatment with vitamin E can partially reverse this process. In theory then, intervention with vitamin E therapy to inhibit atherosclerosis might be more effective in individual diabetics than in nondiabetics. However, as of this date, there are insufficient data on which to base a recommendation of supplemental vitamin E in diabetics."
The book does not discuss the effects of vitamin E on the more prevalent Type II diabetes, but Life Extension’s review of the published literature reveals data that strongly suggests a protective effect.(295-311)
As far as vitamin E and cancer, the book states:
"Cancer is believed to develop as the result of an accumulation of mutations that are unrepaired. DNA is constantly undergoing damage due to interaction with free radicals, and therefore one mechanism by which vitamin E might inhibit cancer formation is by quenching these free radicals. An additional vitamin E preventive mechanism that has been proposed is an effect on the immune system. Many compounds, including vitamin E, have been proposed as anticarcinogens."
The author’s conclusion about vitamin E supplementation, however, is that, “Overall, the epidemiological evidence for an effect of vitamin E on cancer risk is weaker than that for vitamin E and cardiovascular disease. Observational epidemiological studies provide only limited evidence for a protective association and only for some cancer sites.”
The Life Extension Foundation has identified published studies showing a protective effect for vitamin E that were omitted from this book.(312-336) Inclusion of these omitted studies would have provided a more persuasive basis to argue that vitamin E may protect against certain cancers.(337-352)
When it comes to the effects of vitamin E on immune function, the authors relayed the results of studies showing that vitamin E enhances certain immune parameters in the elderly. Nevertheless, their conclusion was, “Whether or not increases in vitamin E intake have any effect on immune function in younger populations remains uncertain. However, the evidence is strong enough to warrant continued investigation.” The Life Extension Foundation cannot understand why the authors point to uncertain effects in younger people as a reason older people shouldn’t take vitamin E to enhance immune function, since it is the elderly who are so vulnerable to death (influenza, pneumonia, cancer, etc.) from immune impairment.
As it relates to cataracts, the authors pointed out five studies showing vitamin E protects against cataract and four studies showing no protective effect. One of the negative studies used only 50 IU a day of vitamin E, whereas most serious supplement takers consume 400-800 IU a day of vitamin E.
The authors pointed to studies showing that vitamin E does not slow the progression of Parkinson’s disease, but omitted studies showing people who take vitamin E have a reduced risk of developing Parkinson’s disease in the first place.
When it came to Alzheimer’s disease, the authors pointed to a controlled study in which 2000 IU a day of vitamin E slowed the progression of the disease. They also pointed to several other studies suggesting that vitamin E might be beneficial in slowing Alzheimer’s disease and Down’s syndrome progression. Omitted were studies showing that vitamin E may reduce the risk of developing Alzheimer’s disease. The conclusions of the authors were as follows:
"Although these results are promising, it is still too early to draw any conclusions about the usefulness of vitamin E
in Alzheimer’s disease and Down’s syndrome."
Tardive dyskinesia is a neurologic disorder that has been shown to respond favorably to vitamin E therapy. The authors report one study showing that 1600 IU a day of vitamin E produced significant benefit in one test score of the disease.
Despite the findings presented in the 512-page book that higher doses of vitamin E provide disease risk reduction and treatment benefits, the authors conclude that only 22 to 33 IU a day of vitamin E from food is needed. The authors, however, raised the maximum safe daily dose of supplemental vitamin E to 1100 to 1500 IU a day, which is consistent with many published findings showing that higher doses are required to prevent chronic disease.
In a review of the toxicity studies on vitamin E, the authors concluded that:
"Humans show few side effects following supplemental doses below 2100 IU a day. However most studies of the possible effects of supplemental vitamin E on human health have been conducted over periods of a few weeks to a few months, so the possible chronic effects of lifetime exposures to such high supplemental levels of vitamin E remain uncertain."
In the press release promoting the 512-page book, however, the National Academy of Sciences twisted the above statement to say that, “extremely large doses may lead to health problems rather than confer benefits.”
The half-truths in the press release promoting the book (and in the 512-page book itself) relating to possible adverse reactions to vitamin E, are egregious. For instance, the authors point to one study in which 50 IU of vitamin E a day increased the risk of hemorrhagic stroke by 50%. The authors then cite numerous other studies showing that 400 to 2000 IU a day of vitamin E produced no increased risk of hemorrhagic stroke. Plus, the authors point to studies showing that supplemental vitamin K abolished any abnormal negative coagulation factors that could be attributed to vitamin E.
The 512-page book states that 1100 to 1500 IU a day of supplemental vitamin E is safe, but the National Academy of Sciences issued a press release indicating that high supplemental doses of vitamin E could be dangerous because of “greater risk of hemorrhagic damage because the nutrient can act as an anticoagulant.”
This distorted press release caused the media to blare warnings that vitamin supplements could be dangerous, when the underlying facts presented in the 512-page book show that in the doses most people take (400 to 800 IU of vitamin E, for instance), the supplement is safe and does not pose any health risk whatsoever.
Right after the National Academy of Sciences’ press release was issued, a new report about vitamin E was presented on April 19, 2000 at a conference entitled Experimental Biology 2000. At the conference, scientists reexamined and unveiled new vitamin E dependent pathways that prevent narrowing of the arteries, which is a major risk factor for cardiovascular disease. The scientists discussed how artery narrowing occurs when platelets, or red blood cells, adhere to and aggregate on artery walls.
“By shutting down a critical enzymatic pathway, vitamin E renders platelets less sticky,” says John F. Keaney, MD, Boston University School of Medicine, “The outcome is less adhesion, less narrowing of the arteries. The benefit is a potential drop in cardiac events.”
Results presented by Ishwarlal Jialal, MD, PhD, of the University of Texas Southwestern Medical Center, reveal that vitamin E also prevents white blood cells from forming arterial plaque. Vitamin E, Dr. Jialal stated, functions as an important antioxidant and anti-inflammatory agent, protecting artery walls from damage that could lead to heart disease.
According to Mohsen Meydani, DVM, PhD, Tufts University, “Vitamin E affects the way a variety of cells circulating in our blood interact with artery walls. As a result, they are less likely to damage and cause inflammation. When artery walls are not narrowed and inflamed, heart disease may be prevented.”
According to another presenter at the conference, Lester Packer, PhD, University of California, Berkeley, “Vitamin E acts like the ‘home-run batter’ on the team of antioxidants, outperforming the others, including vitamin C. While they all work synergistically to protect against cell damage, the others run out of steam much earlier. Because it works longer and harder than the rest, the research indicates vitamin E is the most potent antioxidant in the mix. . . . In fact, the other antioxidants help rejuvenate vitamin E so it works better.”
“The research presented at this conference clearly suggests that meeting daily needs throughout the life cycle can help prevent narrowing of the arteries—a major risk factor for heart disease,” says Maret Traber, PhD, Oregon State University. According to Dr. Traber, the nation may not be consuming enough vitamin E. The results from the 1994-1996 USDA’s Continuing Survey of Food Intake by Individuals indicate that 69% of Americans are not meeting daily dietary needs for vitamin E. Says Dr. Taber, “Because the evidence linking vitamin E to the prevention of heart disease is so strong, dietary supplementation is indicated for these individuals.”
To obtain enough vitamin E from food to attain a reduction in the risk of cardiovascular disease, the scientists stated, you would need to consume nine tablespoons of olive oil, 75 slices of whole wheat bread, 40 almonds or 200 peanuts each day, according to Dr. Taber.
The scientists at the Experimental Biology 2000 conference stated that doses between 50 to 1000 mg of vitamin E may be necessary to reap the potential beneficial effects, though many studies indicate 200 mg (about 300 IU) is sufficient. The scientists stated for those individuals who have difficulty meeting needs through diet alone, supplementation may be indicated. The scientists did acknowledge the National Academy of Sciences’ upper safety threshold of 1100 IU to 1500 IU a day of vitamin E, but indicated that people could obtain the beneficial effects of vitamin E in these dose ranges.
Another omission from the 512-page book is on the issue of gamma tocopherol supplementation.
A group of scientists published a study in the April 1997 issue of the Proceedings of the National Academy of Sciences showing that too much alpha tocopherol vitamin E could displace gamma tocopherol in the tissues and cause undesirable effects. Despite this article about the benefits of gamma tocopherol that appeared in the National Academy of Sciences’ own journal, there is no recommendation in the National Academy of Sciences’ 512-page book for anyone to take supplemental gamma tocopherol or tocotrienol because of “insufficient evidence”at this time. These types of omissions and contradictions are rampant throughout this 512-page book.
What They Said About Beta-Carotene
The book devotes a considerable number of pages to describing the published studies showing that high blood levels of beta-carotene confer significant protection against the development of chronic disease.
First of all, the authors confirm that most studies show a significant antioxidant effect in the body in response to high levels of beta-carotene in the blood. The authors next describe several studies showing that in certain age groups, beta-carotene supplements enhance several parameters of immune function including increasing natural killer cell activity, lymphocyte response to mitogens, and T-helper cell response. The authors caution that the usefulness of these immune markers has yet to be established.
The authors refer to findings related to beta-carotene levels in blood and overall mortality showing that people with the lowest levels of beta-carotene in the blood had a significant increase in their risk of dying. Those with lowest levels of beta-carotene had a 43% increased risk of death from cardiovascular disease, a 51% increased risk of death from cancer, and a 38% increased risk of overall mortality. Other studies cited by the authors corroborated these findings.
As it related to cancer, the authors showed that over a 13-year time period, persons who went on to develop cancer had significantly lower pre-diagnostic carotene concentrations than persons who remained alive and free of cancer. The most consistent result reported by the authors was a lower risk of cancer at several tumor sites in those who consumed relatively large quantities of carotene-rich fruits and vegetables. The consistency of the results was borne out when the authors cited 26 out of 28 humans studies showing that low intakes of fruits and vegetables resulted in the highest rates of lung cancer.
A review of cancers of the oral cavity, pharynx and larynx, showed that fruit and vegetable consumption was associated with a reduced risk of cancer in 13 of 13 studies. Blood analysis in many of these studies consistently showed that beta-carotene levels were lowest in the people who went on to develop cancer.
In looking at cervical cancer risk, the authors reported that over a 15-year period, women with the lowest blood levels of beta-carotene were 2.7 times more likely to contract this form of cancer.
The authors then examined studies showing that diets high in beta-carotene result in reduced risk of cardiovascular disease. One study showed that men with the highest level of beta-carotene in their blood were 36% less likely to develop coronary artery disease. Another study showed that men with the lowest levels of beta-carotene had a 2.64 times greater risk of developing angina pectoris (chest pain caused by obstructed coronary arteries). Still another study of over 39,000 men showed a 29% reduction in coronary artery disease in the group having the highest levels of carotenes. The authors then looked at carotid artery thickness, and found that people with the highest levels of carotenes had the least evidence of carotid atherosclerosis.
When looking at cataract and macular degeneration risk, the authors identified some studies showing that high blood levels of beta-carotene are protective, while other studies showed no benefit. One study(227) that was omitted from the 512-page book showed that those with the lowest serum levels of beta-carotene and vitamin E have a 2.6-fold greater risk of developing senile cataract compared to those with high blood levels of beta-carotene and vitamin E. The conclusions of the scientists who conducted this study were:
"Low serum concentrations of the antioxidant vitamins alpha tocopherol and beta-carotene are risk factors for end stage senile cataract. Controlled trials of the role of antioxidant vitamins in cataract prevention are therefore warranted."
The authors pointed out that most of the positive studies relate to beta-carotene obtained from food, rather than supplement sources. The authors then cited the following three negative trials showing that beta-carotene supplements fail to prevent cancer:
- In long-term heavy smokers, 20 mg a day of synthetic beta-carotene (with or without 50 IU of synthetic vitamin E) led to a higher incidence of lung cancer and no reduction in other cancers compared to placebo.
- In asbestos workers and smokers, 30 mg of synthetic beta-carotene and 25,000 IU of vitamin A led to a higher incidence of lung cancer.
- In a 12-year trial on physicians, 50 mg every other day of synthetic beta-carotene produced no increased or decreased risk on cancer or total mortality. With regard to lung cancer, there was no increase in lung cancer even in smokers who took the beta-carotene supplement for 12 years.
Based primarily on these three negative studies, the authors recommended against supplementation with beta-carotene and suggested instead that beta-carotene be obtained from five servings per day of fruits and vegetables. The authors speculated that there may be nutrients contained in fruits and vegetables other than or in addition to beta-carotene that are responsible the myriad of health benefits associated with high beta-carotene blood levels.
Despite the disease risk reduction benefits of other carotenoids (like lycopene and lutein), the press release the National Academy of Sciences sent to the media cautioned against supplementing with ANY carotenoid. This prompted the media to write articles that would frighten the typical consumer away from supplements containing alpha-carotene, lycopene or lutein. In the 512-page book, a few of the positive studies are revealed about the benefits of these other carotenoids, but most positive reports about lycopene, lutein and alpha-carotene were omitted.
There are a number of other inconsistencies regarding the authors’ evaluation about carotenoid supplementation.
First of all, few consumers take beta-carotene by itself. Beta-carotene is thought to synergistically work with other antioxidants to protect against the free radical damage that can lead to chronic disease. In fact, beta-carotene is one of 60 to 90 different nutrients that health conscious people take to protect against disease. In studies where beta-carotene supplements are combined with other nutrients, the findings are quite different than the three negative studies the authors pointed to.
For instance, in a trial involving 30,000 people, the combination of selenium, higher-dose vitamin E and beta-carotene produced a 13% reduction in overall cancer deaths. Among these receiving this combination of supplements, the risk of dying from lung cancer was reduced by 45%, but the number of people actually getting lung cancer was small and considered to be limited from a statistical standpoint. The significance, however, is that when combinations of higher dose antioxidants are used, better clinical results often manifest. A number of published studies, for instance, show that when beta-carotene is combined with other antioxidants, reductions in indicators of oxidative stress occur, whereas beta-carotene by itself sometimes fails to protect against free radical-induced oxidative stress. Some of these studies involve smokers as well as nonsmokers.
A significant study(353)that was omitted from the book dealt with assessing the risks of heart attack in users of beta-carotene, vitamin C and vitamin E supplements. This study found that the risk of heart attack was reduced by 45% in the group with the highest intake of beta-carotene from supplements or diet compared to the lowest. This cardiovascular disease reduction in those supplementing with beta-carotene was independent of other known risk factors for coronary artery heart attack. Another study on diabetic men showed that a combination of vitamin E, vitamin C and beta-carotene significantly decreases susceptibility of LDL to oxidation. This study is consistent with epidemiological and intervention studies suggesting that antioxidant vitamin use significantly decreases risk for coronary heart disease.
The authors of the 512-page book point to studies showing that beta-carotene by itself does not reduce cardiovascular disease risk, but this does not reflect the fact that most supplement takers use beta-carotene as just one of many cardio-protective antioxidants. The idea of combining antioxidants is not novel. As one scientist stated in a published paper criticizing the negative beta-carotene studies:
"These studies support the hypothesis that the carcinogenic response to high-dose beta-carotene supplementation reported in the human intervention trials is related to the instability of the beta-carotene molecule in the free radical-rich environment in the lungs of cigarette smokers. This is especially possible because smoke also causes decreased tissue levels of other antioxidants, such as ascorbate and alpha-tocopherol, which normally have a stabilizing effect on the unoxidized form of beta-carotene. Nutritional intervention using a combination of antioxidants (beta-carotene, alpha-tocopherol and vitamin C) as anticarcinogenic agents could be an appropriate way to rationally and realistically reduce cancer risk."
Another study(76) that was omitted from the beta-carotene section of the 512-page book involved the treatment of heart attack patients with daily supplements containing 1000 mg a day of vitamin C, 400 IU a day of vitamin E, 50,000 IU of vitamin A and 25 mg of beta-carotene and compared these patients to a placebo group receiving no supplements. The results showed that damaging lipid peroxide levels in serum were 5.5 times higher in the placebo group compared to the group receiving the combination of four antioxidants. Angina pectoris, total arrhythmias and poor left ventricular function occurred less often in the antioxidant group. Cardiac end points were significantly less in the antioxidant group. The conclusions of the doctors conducting the study were:
"These results suggest that combined treatment with antioxidant vitamins A, E, C and beta-carotene in patients with recent acute myocardial infarction may be protective against cardiac necrosis and oxidative stress, and could be beneficial in preventing complications and cardiac event rate in such patients."
A growing number of scientists are recognizing the potential value of combination antioxidant approaches to disease prevention, something that serious vitamin consumers recognized many decades ago. In a published study(354) a review of the scientific literature relating to antioxidants and disease prevention revealed that in the prevention of heart disease, optimal health required “interacting co-nutrients,” and not just a single supplement by itself. The conclusion of the study was that:
"In cardiovascular disease, vitamin E acts as first risk discriminator, vitamin C as second one; optimal health requires synchronously optimized vitamins C + E, A, carotenoids and vegetable conutrients."