|| LE Magazine September 1999
In a historical first, a panel of experts debated the benefits and safety of vitamins E and C to formulate a consensus statement about raising the these nutrients' RDAs. Animal studies have shown that animals with the highest levels of ascorbate and tocopherol in the plasma live longest. While there is total agreement that these vitamins are extremely important for humans as well, human studies have not produced clear-cut results with respect to doses and benefits.
This is particularly true about the doses of vitamin C. Very low ascorbate levels are associated with higher risk of cardiovascular disease and cancer, but there seem to be no additional benefits beyond a certain minimum. Dr. Paul Jacques, while pointing out the flaws in human studies on risk reduction in cataracts with vitamins C and E, nevertheless presented very compelling data on the reduction in cataract incidence with tocopherol supplementation. While supplementing with vitamin C produced only a small risk reduction, when total vitamin C from both diet and supplements was included, the risk of cataracts went down very considerably-perhaps because the fruit and vegetables containing vitamin C also contain other eye-protective nutrients. It was noted that, in general, people who eat the most vegetables-note that it is vegetables rather than fruit-tend to be the healthiest.
Mark Levine of the National Institutes of Health discussed the thorny issue of the ideal dose of vitamin C. He presented a study done on male human volunteers whose diet was first depleted of ascorbate, with different dosages added later. Not much rise in plasma ascorbate levels was found beyond 200 mg per day (by the way, this oral dose is also 100% absorbed, unlike higher doses). Levine also argued that cells saturate before plasma does, at only 100 mg per day. The exception may be the cells of the retina, which seem to require higher concentrations of ascorbate for antioxidant protection. Diabetics appear to need more vitamin C. Smokers may be another category of people with a special need for a higher intake of vitamin C. We also need to examine the issue in regards to women, people with various chronic illnesses and the elderly who, like the diabetics, have higher serum glucose.
A member of the audience pointed out that larger doses of vitamin C may have important benefits in the gastrointestinal tract. Namely, vitamin C helps prevent the formation of carcinogenic nitrosamines. This alone could be a rationale for a higher dosage. A theoretical argument against doses above 1 gram is that some people may tend to develop kidney stones at this level. Epidemiological studies seem to refute this supposition. In fact it might be beneficial to keep the urine more acidic.
There was a lot of agreement, however, on the cardiovascular benefits of vitamin E. A recent Finnish finding that a mere 50 mg of alpha tocopherol considerably lowered prostate cancer incidence and mortality (by 32% and 41%, respectively) has also raised raised the prospect of significant anti-cancer benefits of vitamin E supplementation. In relation to prostate cancer, we badly need a study that combines 200 mg of selenium with various doses of vitamin E. We also need further research on lycopene and ellagic acid as well. Ellagic acid is a polyphenol found in strawberries and cherries; men eating the most strawberries were found to have the lowest prostate cancer risk, lower than that of men eating the most pizza.
In contrast to the lower-dose arguments, a study on LDL oxidation showed that either 2 grams of vitamin C or 400 mg of vitamin E can double the lag time of lipid peroxidation in the plasma. A slight counterargument to this was that even 25 mg of vitamin E has a detectable effect. As for the question whether vitamins C and E have an antioxidant effect on serum lipids in vivo, measuring the peroxidation products in the urine showed that both vitamins did have an in vivo effect, and that the minimum of vitamin E to obtain a detectable effect was 200 mg.
Dr. Margit Traber from the Packer Lab at Berkeley, an expert on vitamin E, presented an interesting brief lecture showing evidence that the body preferentially retains natural alpha tocopherol, while quickly clearing various isomers that exist only in synthetic vitamin E.
Dr. Traber also raised the possibility that vitamin E may raise the risk of hemorrhagic stroke by acting as a blood thinner. Dr. Simin Meydani said that the anti-clotting effect is not seen at doses below 800 mg, and that in her opinion there was no increased risk. In fact aspirin presents a lot more risk in this regard. The panel reached a consensus that supplementation with vitamin E is safe.
It was also pointed out that perhaps limiting the discussion of vitamins to their antioxidant effects is too narrow, since these fascinating compounds also have a wide range of non-antioxidant effects, such as anti-inflammatory action and the newly discovered role in gene expression. The label "antioxidants" may be too narrow, just as the term "sex hormones" does not begin to indicate the enormous metabolic role of those crucial steroids.
One member of the audience raised an interesting point about the importance of how experts act rather than what they say. He suggested that the public is aware that scientists and physicians take supplements of vitamin E themselves, even though they may sound very conservative in their official statements. Consequently the public is likely to conclude that what really counts is what the scientists do to safeguard their own health, rather than what they say, and act on that basis.
Some health enthusiasts would no doubt find the overall tone of the panel to be conservative and minimalist. The arguments for the relatively low dosage of vitamin C were fairly convincing, however. In regard to vitamin E, it was disappointing to see no weight given to the finding that it takes a minimum of 400 mg to protect LDL cholesterol from oxidation, and that levels even higher than that might be more optimal. No mention was made of the Packer Lab findings that vitamin E can dramatically slow down aging at the cellular level.
Ultimately, the panel reached the conclusion that the RDA for vitamin C should be raised to 200 mg/day, and this intake is best secured from vegetables and fruit, since these provide additional valuable nutrients. However, the panel concluded that the RDA for vitamin E should likewise be raised to 200 milligrams a day, and that only supplements can provide this level. There is simply no safe and practical way to obtain this amount from the diet. In effect, this is an admission that even the best possible diet cannot supply all the nutrients needed for optimal function, particularly by the elderly.
The irony of the situation is that people who take supplements already tend to eat a good diet. It is the poor and the smokers who most need to take supplements. Durk Pearson raised a provocative point that it is expensive for the average family to consume the recommended five or more servings of vegetables and fruit, especially in winter. This is obvious if we think of blueberries. Thus, relatively inexpensive supplements might have a considerable impact on the health of the less affluent population. Dr. Bruce Ames also suggested that officially recommending a multivitamin might be a good place to start in the hope of improving the health of the less-educated. Since obesity and smoking are also more prevalent among these segments of the population, such a recommendation would be a band-aid approach, but at least it would be a start.
Ultimately, though, antioxidant intake can only do so much. Taking antioxidants is basically aimed at trying to lower the degree of damage that comes from free-radical production. We also need to do something about caloric consumption, smoking, and excess levels of stress. In other words, we need to look at the initiation end of the spectrum. Most production of free radicals takes place in the mitochondria, so it is vital to preserve efficient mitochondrial metabolism. Unfortunately, at this point calorie restriction remains the only proven way to extend maximal life span. However, we are gaining knowledge of compounds such as lipoic acid and carnitine, already documented to restore mitochondrial efficiency.
At the threshold of real breakthroughs
Many participants have commented on the excellent and exciting quality of this year's AGE conference. One of the problems facing American gerontology has been the official policy that the aging process should be studied, but not for the purpose of intervention. This conference, however, presented a wealth of data with inescapable implications for the prevention of aging-related degenerative disorders such as Alzheimer's disease, heart disease, immune decline, cancer, cataracts, osteoporosis and more. In fact, a whole day was devoted to various approaches for altering the aging process.
Not acting on our growing knowledge of how to prevent the suffering and disability associated with aging would be highly questionable from the point of view of ethics. Even simple steps, such as recommending the daily consumption of blueberries or other berries and raising the RDA's for various nutrients, might have extremely significant impact on public health. The fact that the panel of experts officially recommended raising the RDA's for vitamins C and E is thus of historical importance. It amounts to a public admission by the scientific community that we can do something about aging.
In addition, there is now little doubt that the near future will bring further exciting breakthroughs in the form of gene therapy, anti-glycation products, and ways to mimic calorie restriction. At long last, we can be truly optimistic about our chances to live a very long, vigorous and disease-free life.
| Blueberry Power:
Phytonutrients and the Brain
It is well known that certain foods such as berries and spinach provide a wealth of potent antioxidants. Eating a cup of blueberries, for instance, can double a typical American daily antioxidant intake. This may have tremendous implication for the prevention of free radical-related disorders, including neurodegenerative diseases.
One of the phenomena of aging is a decreased release of dopamine, a neurotransmitter crucial for mood, motivation and motor control. Higher dopamine may also indirectly lead to lower insulin levels. It is interesting that some proven anti-aging agents seem to work precisely by increasing dopamine levels. A team of researchers from Tufts University presented evidence showing that a diet enriched with blueberries can increase dopamine release in rats. The practical consequence of this was improved performance on motor tests, such as the difficult task on staying on a rotating rod.
Blueberries contain various anthocyanins, a subcategory of flavonoids responsible for the deep blue color of blueberries. Anthocyanins are also known to be potent antioxidants, and have an anti-inflammatory action as well. In addition, they have been found to increase membrane fluidity and to act as blood thinners.
In response to a question about the relative antioxidant potencies of blueberries as compared to bilberries, the speaker said that some of the wild varieties of blueberries were "almost as good" as the European bilberries. Her team may eventually run a comparison between blueberry extract and bilberry extract.
There is a fruit that comes close to the antioxidant power of blueberries: prunes. A few prunes a day might indeed keep Alzheimer's disease away, but, as the Tufts researchers pointed out, prunes have a PR problem. Blueberries, on the other hand, "are elegant, like Princess Di."
Spinach was also shown to be effective in preventing age-related dopamine decrease, and maintaining the ability to remove calcium ions from the cell. Spinach helped with water maze performance, possibly because this task requires visual input, and spinach is known to preserve vision.
Rick Weindruch raised an interesting point concerning the use of a purified diet in nutritional research. He suggested that the purified diet is so deficient in antioxidants that the dramatic effect of the blueberry-enriched diet might be due to making up for these deficiencies. While the effect of frequent blueberry consumption might indeed not be as dramatic in humans who already eat an antioxidant-rich diet, the documented benefits of anthocyanins seems at least as promising as those of green tea polyphenols.
Considering the high cost of blueberries, I asked a couple of chemists if frozen blueberries, or frozen berries in general, have the ability to provide benefits similar to those of fresh berries. The chemists agreed that frozen berries should still provide considerable benefits. -IG