Science & Research
Magazine
2000
August
A Critical Analysis of The National Academy of Sciences' Attack on Dietary Supplements

Life Extension Magazine®

A Critical Analysis of The National Academy of Sciences' Attack on Dietary Supplements

Putting anti-supplement reports under the microscope.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in October 2024. Written by: William Faloon.

William Faloon

Consumers of vitamin supplements have been hit with a lot of negative press lately, and The Life Extension Foundation has been on the forefront in evaluating whether these anti-supplement reports have scientific merit.

Two months ago, we examined a presentation made at an American Heart Association meeting where a doctor stated that compared to non-supplement users, vitamin C takers had higher rates of carotid artery wall thickening. In response to this claim, The Foundation conducted an identical test on 30 members who had been taking very high doses of vitamin C (and many other nutrients) for many years. Results showed that these vitamin C supplement takers as a group had remarkably healthy carotid arteries compared to the average population. The group we tested were significantly older than the people evaluated by the American Heart Association. Our group should have had more evidence of carotid atherosclerosis and thickening. Instead, Foundation members as a group were found to have no indication of increased carotid wall thickening in response to their very high vitamin C intake. We also showed how this American Heart Association presentation, which looked at people taking relatively low potencies of vitamin C (500 mg a day and less), had no relationship to Life Extension Foundation members who are taking very high doses (2000 mg a day and higher) of vitamin C along with other nutrients that have been shown to reduce the risk of atherosclerosis.

On April 10, 2000, the National Academy of Sciences issued a press release that stated:

"Insufficient evidence exists to support claims that taking megadoses of dietary antioxidants, such as selenium and vitamins C and E, or carotenoids, including beta-carotene, can prevent chronic diseases."

This report received widespread media attention, and many news articles questioned the value of dietary supplements altogether. The National Academy of Sciences’ press release was based on the conclusions of a 512-page book that ostensibly looked at all the published scientific literature about the intake of certain nutrients and subsequent risk of developing disease.

Contradiction and Omission

The name of this 512-page book is Dietary Reference Intakes For Vitamin C, Vitamin E, Selenium and the Carotenoids. This book contains a startling contradiction. The negative conclusions drawn by the authors are opposite to the positive findings about the supplements that are described in the very same book. This contradiction is not surprising, considering that the book is authored by two “committees” comprised of 40 members.

The book omits published studies about antioxidants. It also fails to take into account that supplement takers usually consume a wide variety of nutrients to protect their health, not just vitamin C or E alone. The authors of the book did capably describe many of the positive studies indicating a disease risk reduction in response to a particular supplement. But it turns pessimistic when even one study fails to confirm the many positive ones. An example of the pessimistic tone can be seen in the following quotation that appeared on page 187:

"A large and growing body of experimental evidence suggests that high intakes of vitamin E may lower the risk of some chronic diseases, especially heart disease. However, the limited and discordant clinical trial evidence available precludes recommendations at this time of higher vitamin E intakes to reduce disease risk."

This statement is followed by numerous pages itemizing the studies showing that vitamin E prevents chronic diseases. For instance, the author’s analysis of observational human studies shows “risk reductions of 30% to 60%” in coronary heart disease risk in those consuming the highest amounts of vitamin E. Despite these reductions in heart attack risk, the authors stated, “As of this date, there are insufficient data on which to base a recommendation for vitamin E as a heart disease preventive to the general population.” The authors did, however, raise the “safe” upper dose limit of vitamin E to 1500 IU a day.

It should be emphasized that the book essentially supports dietary supplementation for the purpose of disease reduction. In fact, this book makes a strong case that these supplements (vitamin C, vitamin E, selenium and the carotenoids) produce significant health benefits. The negative twist, however, comes when the authors conclude that there is “insufficient evidence” to recommend that the general population supplement with these nutrients.

What are "Dietary Reference Intakes"?

The primary purpose of this book is to establish new government recommended daily allowances for vitamin C, vitamin E, selenium and the carotenoids. The new term for RDA is “Dietary Reference Intakes,” which is defined as “reference values that are quantitative estimates of nutrient intakes to be used for planning and accessing diets for apparently healthy people.”

One problem with this definition of “Dietary Reference Intakes” is that it fails to take into account that as people age, they are no longer “apparently healthy.” While some aging people optimistically claim to be as healthy as ever, aging wreaks havoc in every cell of the body. The authors recognized their limits in setting new “Dietary Reference Intakes” by admitting that they were not able to estimate the amount of these nutrients “required by children, adolescents, lactating women and the elderly.”

Unfortunately, when the press reported on this book, it failed to mention the limitations that the authors themselves placed on their conclusions. In setting these new “Dietary Reference Intakes,” the authors emphasized their limitations by stating that “scientific judgement was required for evaluating the evidence and in setting the reference values.”

“Scientific judgement” is a fancy way of saying that these new recommendations are based on the arbitrary conclusions of two committees. This subjective approach should not be confused with bona fide science, as an evaluation by another group could yield completely different conclusions.

The vitamin E recommendations are a good example of what “scientific judgement” really means. Those concerned about protecting their health take vitamin E because of studies showing “risk reductions of 30% to 60%” in heart attack risk. Yet, in the “scientific judgement” of the committees, there is still “insufficient data” to recommend that people actually take vitamin E supplements.

What They Said About Vitamin C

While increasing the maximum safe daily intake of vitamin C to 2000 mg a day, the authors of the 512-page book set the recommended daily intake of vitamin C as follows:

Males 90 mg
Females 75 mg
Smokers 35 mg additional
(to compensate for the increased “oxidative stress” smoking induces)

These doses of vitamin C, the authors noted, “should maintain near maximal neutrophil ascorbate concentrations with little urinary excretion.”

Supplement users, however, are taking vitamin C for reasons other than to maintain their “neutrophil ascorbate concentrations.” (Neutrophils are specialized immune cells that require vitamin C to kill pathogens and still maintain their cellular integrity.)

As was the case with vitamin E, the 512-page book contains numerous pages of summaries of published papers indicating significant health benefits in response to vitamin C supplementation. One study describes that when smokers were supplementing with 2000 mg a day of vitamin C, “the adhesion of their monocytes to endothelium decreased to that seen in non-smokers.” (Monocyte adhesion is an initial factor leading to the development of atherosclerosis). Instead of recommending that smokers take 2000 mg of vitamin C as the people did in the study, the authors suggest that smokers obtain only 110 to 125 mg per day of vitamin C.

This kind of illogical recommendation is pervasive through the vitamin C chapter. For instance, page 103 of the book states:

"Numerous investigators have reported a beneficial effect of high-dose vitamin C administration, either orally or intraarterially, on vasodilation. This beneficial effect of vitamin C is most likely related to its antioxidant effect. Vitamin C improves endothelial function and vasodilation, possibly by scavenging superoxide radicals, conserving intracellular glutathione, or potentiating intracellular nitric oxide synthesis."

Strangely, the authors interpret these kinds of positive findings as an indication to not take high doses of vitamin C. The 512-page book makes it clear that high doses provide the beneficial effect of vitamin C on the arterial system. The contradictory conclusion, however, is that people only need between 75 and 125 mg of vitamin C a day. These types of contradictions may be explained by the fact that many different people were involved in writing the 512-page book.

When it comes to vitamin C and cancer, the authors again provide substantial data from the published literature to show both potential risk reduction benefit, definitive risk reduction benefit or no risk reduction benefit. Since some studies show no risk reduction benefit, the authors advise against vitamin C supplementation for the purpose of cancer prevention.

A partial list of supplements typically consumed by the serious vitamin consumer

Coenzyme Q10
Alpha lipoic acid
Ginkgo
Grape-seed
Green tea
Vitamin A
Vitamin B1
Vitamin B2
Vitamin B3 (in the form of niacin and niacinamide)
Vitamin B5
Vitamin B6
Vitamin B12 (in the form of methyl and cyanocabolomin)
Folic Acid
Biotin
Vitamin C (and both water and fat soluble forms)
Vitamin D
Vitamin E (in the form of alpha and gamma tocopherol or tocotrienol)
Fatty acids (fish, flax or Perilla oils, gamma linolenic acid, etc)
Choline
Inositiol
Magnesium
Zinc
Selenium
Molybdenum
Manganese
Lutein
Alpha carotene
Beta carotene
Lycopene
Calcium
Trimethylglycine (TMG)
Acetyl-l-carnitine
Chromium
Bilberry
Low-dose aspirin
DHEA
Melatonin
Taurine
N-acetyl-cysteine
Lysine
Silymarin
Potassium

Each one of the above nutrients has been shown to provide specific health benefits, and many work together in a synergistic fashion to protect against the onset of degenerative disease.

The same hold true with immune function. Some studies show positive benefit, others show no benefit. Therefore, according to the authors, vitamin C supplementation is not recommended.

On page 125 of the 512-page book, the authors offer the following conclusion regarding vitamin C and cancer:

"Although many of the above studies suggest a protective effect of vitamin C against specific cancers by site, the data are not consistent, or specific enough to estimate a vitamin C requirement based on cancer."

When evaluating the potential benefit of vitamin C to prevent cataract, the authors describe the following studies:

490 mg a day of vitamin C resulted in a 75% reduction in cataract compared to doses less than 125 mg a day.
300 mg a day of vitamin C associated with a 70% reduction in cataract.
Higher intake of vitamin C is associated with a 20% reduction in cataract.
No association found in cataract risk in people taking 260 mg a day of vitamin C compared to those taking 115 mg a day. (This is considered a negative study.)
Cataract risk was 45% lower in nurses taking vitamin C supplements for ten years, but no effect was observed for those taking vitamin C for less than ten years.

(This, too, is considered a negative study by the authors.)

Based on the above studies, the authors of the 512-page book concluded:

"Although many of the above studies suggest a protective effect of vitamin C against cataracts, the data are not consistent or specific enough to estimate the vitamin C requirement based on cataract.."

When evaluating the effects of vitamin C on asthma and chronic obstructive pulmonary disease, again the authors cite studies showing a significant protective effect, but their conclusion is:

"Although many of the above studies suggest a protective effect of vitamin C against asthma and obstructive pulmonary disease, the data are not consistent or specific enough to estimate the vitamin C requirement based on asthma or pulmonary disease."

In the summary, the authors make an argument that optimal cardiovascular and cancer protection may occur with total daily vitamin C intake of 90 mg, but state it may be difficult to conduct large-scale clinical studies in the U.S. and Canada to prove this because it would be hard to isolate a group that consumes less than 90 mg a day of vitamin C. The authors go on to provide examples of vitamin C protecting against a wide range of other diseases, but discount all these studies as “insufficient” to warrant wide scale supplementation.

While the 512-page book cited many published studies documenting the beneficial effects of vitamin C, there were serious omissions. The most significant study that was omitted was published in the American Journal of Clinical Nutrition in August 1996. This study examined 11,178 elderly people over a 9-year period. The results of the study showed that those who took high potency supplements of vitamin C and E had an overall 42% mortality risk reduction. Said differently, there were 42% fewer people dead over a nine year period who took high potency vitamin C and E supplements compared to those taking low potency or no supplements.

In addition, we discovered numerous positive studies about vitamin C that met the criteria for inclusion in the 512-page book (as defined by the authors) which were ignored.(1-166) Had these positive studies been included, they would have erased the doubt the authors expressed about the disease prevention potential of vitamin C.

What Are Vitamin C's Side Effects?

The authors speculated about the potential toxic effects of vitamin C, but concluded that the extent of toxicity appears to be diarrhea in some people at high doses. Had the media read the 512-page book, instead of relying on the biased press release that implied a health risk to vitamin C supplements, the media would have reported that high doses of vitamin C are remarkable safe.

What They Said About Selenium

Selenium is a mineral used to protect against a wide range of diseases, but the authors of the book only discussed the role of selenium as an antioxidant and cancer preventive agent.

The authors omitted from discussion studies showing selenium protects against heart disease,^167-197 studies showing selenium protects against hepatitis viral damage,^198-206 studies showing selenium slows progression of HIV,^207-224 studies showing that selenium protects against cataract,^225-234 and numerous other studies showing definitive health benefits in humans.^235-273 These studies were omitted as if they did not exist.

Here is what the 512-page book did report about studies on selenium and cancer on pages 290-291:

"Subjects assigned a daily combination of selenium (50 mcg), beta-carotene (15 mg) and vitamin E (30 mg) achieved a significant (21 percent) decrease in gastric cancer mortality, resulting in a significant 9 percent decline in all-cause mortality. However, these results cannot be attributed to selenium alone, because the individuals consumed selenium in combination with beta-carotene and vitamin E."

"200 mcg a day of selenium administration in the form of yeast showed no effect on recurrence of non-melanoma skin cancer compared to placebo group but significantly lower rates of prostate, colon and total cancer were observed among those assigned to the selenium group." (This was considered a negative study by the authors)

"The risk of prostate cancer for men receiving 200 mcg a day of selenium was one-third that of men receiving placebo."

While numerous published studies exist to support the protective role of selenium against cancer, the authors choose only the above three studies to question the value of selenium supplementation. The three studies cited above, however, are quite positive, yet the authors twisted their meaning to imply the studies showed no definitive cancer risk reduction benefit.

As far as cancer and selenium are concerned, the 512-book concluded with the following information on page 291:

"Results of these three studies are compatible with the possibility that intakes of selenium above those needed to maximize selenoproteins have an anti-cancer effect in humans. These findings support the need for large-scale trials. They cannot, however, serve as a basis for determining dietary selenium requirements at this time."

The overriding error with the above “conclusion” is that it failed to incorporate the findings of a large-scale clinical study published in the December 25, 1996 issue of the Journal of the American Medical Association showing that compared to placebo, those people receiving a 200 mcg supplement of selenium had a 37% reduced risk of cancer incidence and a 50% reduction in cancer mortality. This 9-year study is exactly what the authors of the book said needed to be done to validate the anticancer benefits of selenium. The fact that this positive and well recognized study was omitted seriously questions the credibility of this 512-page book.

The authors omitted studies indicating that selenium may be effective as an adjunctive cancer therapy. One study²⁷⁴ showed that when rats with mammary tumors where given moderate doses of supplemental selenium, a significant inhibition of cancer-associated angiogenesis occurred. Tumors require new blood vessels to sustain their rapidly proliferating cancer cells. Substances that inhibit the formation of new blood vessels are called antiangiogenesis agents, and these substances are being extensively studied as potential cancer therapies. Selenium’s anti-angiogenesis property may be one reason why it has been shown to reduce cancer mortality rates in humans already diagnosed with cancer.

In Germany, selenium is being used as an adjunctive cancer therapy. In a study²⁷⁵ omitted from the 512-page book, German doctors evaluated the effects of selenium supplementation in women with breast and gynecological cancers. Here is a summary of their findings:

"In pilot studies with low-dose selenite (up to 300 micrograms a day) the patients reported a better quality of life. Side effects were not reported. Analysis of the immune system reveal a stimulation of B19 lymphocytes and natural killer cells. In Germany, a country with selenium deficiency, clinical studies are now carried out on the effects of selenium as a drug to reduce side effects of chemo- and radiotherapy, enhance quality of life by reducing toxic side effects and help to restore immune function."

Another study that was omitted from the 512-page book showed that rectal cancer patients treated with radiation and chemotherapy benefitted from high dose selenium supplementation. In this study, 2000 micrograms of selenium were given after every course of chemotherapy and 400 micrograms of selenium given daily during irradiation. The doctors were able to verify a protective effect and concluded that “oral selenium intake in rectal cancer patients is easily tolerated with no side effects.”²⁷⁶

Another study²⁷⁷ omitted from the 512-page book measured serum levels of selenium in those diagnosed with colon cancer. The results of this study showed that colon cancer patients with low serum levels of selenium had significantly shorter survival time compared to patients with higher selenium levels. In a related study²⁷⁸ also omitted from the 512-page book, patients with colorectal cancer or adenoma had very low serum selenium levels compared to age-matched healthy controls. The doctors conducting this study stated:

"These results indicate that low selenium status is strongly associated with colorectal neoplasia (including extension and severity of the disease) and that it may not only be a result but also one of tumorogenic factors. That means that selenium supplementation could be important in prevention or even adjuvant therapy of colorectal cancer."

Another significant study²⁷⁹ sponsored by the National Cancer Institute, (but omitted from the 512-page book) showed that the combination of selenium and vitamin E or the combination of n-acetyl-cysteine and vitamin A analogs may be effective in protecting against lung cancer.

Another omitted study²⁸⁰ reviewed the molecular mechanisms of selenium’s actions in the body and concluded that:

"Higher levels of selenium supplementation can be expected to affect other functions related to tumorigenesis: carcinogen metabolism, immune function, cell cycle regulation and apoptosis. Thus, according to this 2-stage model of the roles of selenium in cancer prevention, even individuals with nutritionally adequate selenium intakes may benefit from selenium supplementation."

Despite questioning the health benefits of selenium, the authors of the 512-page book increased the maximum safe daily amount of selenium intake to 400 mcg per day. Many vitamin takers, of course, have been consuming 400 mcg a day and higher of selenium for decades without evidence of toxicity (selenosis). Since published studies show 200 mcg a day of selenium results in significant (up to 50%) reductions in cancer mortality,^281-288 one might think the recommended allowance would be increased to 200 mcg a day, but that was not the case. Instead, the authors concluded the following on page 319:

"Limited evidence has been presented that intakes of selenium greater than the amount needed (55 mcg) to allow full expression of selenoproteins may have chemopreventive effects against cancer. Controlled intervention studies are needed to fully evaluate selenium as a cancer chemopreventive agent."

The problem with the above conclusion is that only “limited evidence” was presented in the book about selenium’s health benefits, as the authors omitted most of the positive published studies showing that selenium prevents cancer and is effective in treating and preventing many other diseases.

Selenium may even reduce the incidence of heart attack. Another study¹⁸⁰ omitted from the book involved 3387 men aged 53-74 followed over a three year time period. Men with the low serum levels of selenium had a 70% greater risk of coronary heart disease compared to those men with higher selenium levels, and this finding was independent of other risk factors. However, not all studies are consistent. A five-year study¹⁹² of 1,110 men aged 55 to 74 years showed that the risk of stroke was 3.7 times greater in the low selenium group compared to the high selenium group. However, in this same study, high selenium levels did not produce a statistically significant reduction in the rate of heart attacks. So selenium was shown to protect against heart attack in one study, and stroke (but not heart attack) in another study. Since these findings are inconsistent, the authors do not recommend people supplement with selenium.

One finding that shows up repeatedly is that adults living in selenium deficient geographic areas have severely reduced life spans. Heart muscle damage is common at autopsy in these selenium-deficient cases. In 25 cities in the United States, low selenium correlates with high rates of heart attack and cancer.177 In trying to understand the mechanisms by which selenium protects against heart disease, scientists have looked at the effects of selenium in protecting the enothelial lining of the arterial system against oxidative damage, protecting blood cells against abnormal aggregation, and by inhibiting LDL cholesterol oxidation. Moreover, selenium prevents toxic effects of cadmium and mercury, and helps to modulate the active transport of calcium out of the arterial system.¹⁸³

One study¹⁸⁶ pointed out that human platelets need selenium to create an important antioxidant enzyme called glutathione peroxidase. Platelets of selenium-deficient subjects show increased aggregation, thromboxane B2 production and synthesis of the lipoxygenase-derived compounds. In these deficient subjects, selenium administration increases platelet glutathione peroxidase activity and inhibits platelet hyperaggregation and leukotriene synthesis. In addition to its potential effects in protecting against cardiovascular events, selenium appears to protect the body against damage caused by hepatitis B, hepatitis C and HIV. In one study on HIV patients¹⁹¹ selenium deficiency was associated with myopathy, cardiomyopathy and immune dysfunction including oral candidiasis, impaired phagocytic function and decreased CD4 T-cells.

The book omitted any information relating to the role of selenium in preventing cataract. One of these omitted studies²²⁶ showed that when supplemental selenium was given along with beta-carotene and vitamin E, there was a statistically significant 36% reduction in the prevalence of nuclear cataract. The book omitted any reference to the protective effect selenium confers against primary liver cancer and infection with the hepatitis B or C virus. One notable study that was omitted¹⁹⁸ involved a staggering 130,471 people followed for eight years. The group who received supplemental selenium had a 35.1% reduction in the incidence of primary liver cancer compared to the placebo group which did not receive selenium. When selenium supplementation was discontinued, incidences of primary liver cancer began to increase, indicating that continuous intake of supplemental selenium is essential to sustain its protective effect against liver cancer. In a sub-group of this study that evaluated 113 patients infected with the hepatitis B virus, the daily intake of 200 mcg of selenium resulted in zero rates of liver cancer, compared to 7 liver cancers in the placebo group (not receiving selenium supplements). When the selenium group stopped taking the selenium supplement, primary liver cancer rates began to increase.

Another omitted study²⁸⁹ examined the association between plasma selenium levels and risk of hepatocellular carcinoma among chronic carriers of hepatitis B and/or C virus in a cohort of 7,342 men. This 5.3 year study showed that those with low blood selenium levels were 47% more likely to develop hepatocellular carcinoma (primary liver cancer) compared to those with higher levels of selenium.

Also omitted was a small case history report²⁹⁰ showing substantial benefit to treating advanced hepatitis C patients with a combination of alpha lipoic acid, silymarin and selenium. Here is what the physician reported regarding his clinical observations:

"The triple antioxidant combination of alpha-lipoic acid, silymarin and selenium was chosen for a conservative treatment of hepatitis C because these substances protect the liver from free radical damage, increase the levels of other fundamental antioxidants, and interfere with viral proliferation. The 3 patients presented in this paper followed the triple antioxidant program and recovered quickly and their laboratory values remarkably improved. Furthermore, liver transplantation was avoided and the patients are back at work, carrying out their normal activities, and feeling healthy."

The physician noted that supplementation with these three nutrients is relatively inexpensive compared to more than $300,000 for liver transplant surgery. He also noted that other problems with liver transplant surgery include a shortage of available livers, reinfection of the new liver with residual virus, and high mortality rates associated with the procedure including greater risks of cancer from the immune-suppressing drugs given to suppress organ rejection.

In another omitted study,²⁹¹ when selenium, n-acetyl-cysteine and interferon were used to treat hepatitis C, selenium and n-acetyl-cysteine showed no enhanced effect compared to interferon alone. When 544 IU a day of vitamin E was added to the selenium, n-acetyl-cysteine and interferon group, however, complete response occurred in six out of eight patients. Compared to the group receiving interferon alone, the group obtaining the vitamin E, selenium, n-acetyl-cysteine and interferon showed a 2.4 greater chance of obtaining a complete response and had a significant reduction in viral load. This study helps substantiate the need to use multiple antioxidant nutrients in treating disease. While selenium by itself has been shown to protect against hepatitis-induced liver cancer, this study showed the importance of adding other antioxidants (vitamin E and n-acetyl-cysteine) to put active hepatitis infection into remission when combined with interferon.³⁰⁰

Yet another omitted study²⁰⁶ involving 20,847 people showed that those supplementing with selenium showed a 70% reduction in becoming infected with the hepatitis B virus compared to surrounding populations not receiving supplemental selenium.

Numerous published studies demonstrate a molecular basis for how selenium may protect against hepatitis infection and subsequent development of liver cancer, yet the authors of the 512-page book chose to omit this plethora of research as if it did not exist.

Selenium has shown efficacy in slowing the progression of HIV infection. One study²⁰⁷ showed that low plasma level of selenium in children with AIDS is an independent predictor of mortality, and appears to be associated with faster disease progression. This study showed increased mortality greater than 5-fold in children with low selenium levels. Another study²⁹² found that selenium deficiency is an independent predictor of survival in adults with HIV-1 infection. These two studies were omitted from the 512-page book.

Also omitted was a study²¹⁰ indicating that supplementation with selenium may help to increase the enzymatic defense systems in HIV-infected patients and slow disease progression.

In a study²¹³ funded by the FDA, supplemental selenium was shown to have a positive effect in boosting various immune parameters that are suppressed by the HIV virus. The doctors conducting this study stated:

"Taken together, these results suggest that selenium supplementation may prove beneficial as an adjuvant therapy for AIDS through reinforcement of endogenous antioxidative systems."

The sheer volume of studies showing selenium to be an effective adjunctive therapy against HIV infection is overwhelming, but none of these studies were reported on in the 512-page book. Its not just people infected with the HIV virus who are immune compromised. A pioneering study published in The Lancet²⁹³ found that seniors taking modest doses of a multivitamin/ multimineral supplement containing zinc and selenium showed a general reduction in infection and required antibiotics for significantly fewer days. A more recent study brings the effect of these two minerals into sharper relief. This well-designed study (randomized, placebo-controlled, double-blind) found that seniors taking zinc and selenium had significantly fewer infections over a two year period, but that vitamin supplementation alone did not have a major effect.²⁹⁴ The zinc and selenium supplement cut the number of infections by nearly two thirds compared to placebo. A follow-up study demonstrates that seniors supplementing with zinc and selenium show improved antibody response to the flu vaccine.²⁶⁸

Despite the enormous health benefits that selenium supplementation has been shown to confer in humans suffering from chronic disease or normal aging, the authors omitted these studies from the 512-page book, which would lead people suffering from these diseases to believe there is no value in taking supplemental selenium.

While the authors increased the safe total daily intake of selenium to 400 mcg and cited a few of the studies showing selenium may prevent cancer, the authors’ “conclusion” is that 55 mcg a day from diet is adequate. This “conclusion,” recommending only 55 mcg of selenium a day, contradicts the published studies showing that 200 mcg a day from supplemental selenium confers protection against the development of cancer and other diseases.

The authors stated that “insufficient evidence” existed to warrant selenium supplementation for the prevention of cancer, yet the authors omitted most of the positive evidence showing that selenium is effective in preventing cancer.

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 study²²⁷ 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 study³⁵³ 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 study⁷⁶ 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 study³⁵⁴ 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."

What About The Other Carotenoids?

In recommending against taking beta-carotene supplements, the authors also recommended against supplementation with all other carotenoids (such as lycopene and lutein). Their basis was that “insufficient evidence” existing to establish an effective daily requirement for these other carotenoids.

The authors presented several positive studies showing high levels of lycopene in the diet or in serum resulted in reduced risks of cancer. One study showed that daily intake of 6.46 mg of lycopene resulted in a significant reduction in the risk of prostate cancer.

The authors then site in the 512-page book two additional positive overview studies showing a multitude of potential health benefits of lycopene and one no-response study conducted in Asia in which blood levels of lycopene did not affect prostate cancer risk. The authors attributed the lack of effect in this no-response study to the fact that tomato products are not widely consumed in Asia, and the test subjects as a group, therefore, had very low lycopene levels to begin with.

The authors related the results of many studies showing that women with low carotenoid status have about three times greater risk of cervical cancer.

Omitted were several hundred studies showing specific reductions in disease risk in those who consumed high amounts of lycopene, lutein, alpha- carotene and/or other carotenoids in food or supplement form.^355-555 These omissions would lead the reader to believe there is only limited positive data about the health benefits of the “other carotenoids.”

The authors caution against taking carotenoid supplements, but fail to discuss studies indicating that when combined with other supplements, the carotenoids exhibit potent disease-prevention effects. One such study⁴¹³ examined the effects of lycopene and vitamin E on the growth of two human prostate cancer cell lines. Lycopene by itself was not a potent inhibitor of prostate cancer cell growth, but when combined with vitamin E, “a strong inhibitory effect of prostate carcinoma cell proliferation, which reached values close to 90%, was observed.” The scientists noted the synergistic effect of lycopene and vitamin E.

Another omitted study³⁸⁰ showed that men with the highest blood levels of lycopene had a 25% reduced risk of any type of prostate cancer and a 44% reduction in their risk of aggressive prostate cancer. An interesting paradox to this study was that in men with low lycopene, beta-carotene supplements were associated with risk reductions comparable to those observed with high lycopene. The doctors concluded this study by stating:

"These data provide further evidence that increased consumption of tomato products and other lycopene-containing foods might reduce the occurrence or progression of prostate cancer."

The authors omitted a study³⁷⁰ that examined the effect of daily consumption of a tomato juice supplemented with vitamin C (600 mg), vitamin E (400 IU, or 400 mg) and beta-carotene (30 mg) on various indexes of lipid peroxidation in smokers. The findings showed that relative to the placebo juice (that contained no added vitamins), the vitamin-supplemented juice resulted in a significant decrease in measurements of lipid peroxidation such as breath-pentane excretion as well as a significant improvement in the resistance of LDL to oxidation. The scientists conducting this study concluded:

"This study thus indicates that an antioxidant-supplemented drink can reduce lipid peroxidation and susceptibility of LDL to oxidation in smokers and may ameliorate the oxidative stress of cigarette smoke."

Another omitted study discussed the synergistic benefits of carotenoids³⁷¹ in protecting against free radicals. This study ranked the various carotenoids based on their antioxidant ability and found that lycopene was the most potent. The scientists noted that:

"Mixtures of carotenoids were more effective than the single compounds. This synergistic effect was most pronounced when lycopene or lutein was present. The superior protection of mixtures may be related to specific positioning of different carotenoids in membranes."

Also omitted were studies showing protection against immune cell oxidative stress when serum lycopene and other carotenoid levels were increased. ^369,374 One study showed a 45% increase in cellular glutathione in response to lycopene supplementation.⁴²¹

The authors stated virtually nothing about the benefits of lutein in protecting against certain cancers. The authors did relate studies showing that those who consumed high amounts of lutein and zeaxanthin had “a 60% lowered risk” of macular degeneration. Other studies related by the authors showed high intakes of lutein and zeaxanthin reduced cataract risk by about 20%. Despite these revelations, the authors concluded that:

"Insufficient Macular Pigment Optical Density studies have been conducted to date to make recommendations relative to dietary intakes of lutein and zeaxanthin."

As it relates to cardiovascular disease, the authors omitted a study⁵⁰⁵ showing that in elderly people, high serum levels of lycopene reduced the risk of aortic atherosclerosis by 45% in nonsmokers and by a staggering 65% in smokers. The scientists concluded that:

"Our findings suggest that lycopene may play a protective role in the development of atherosclerosis."

Other studies^433,438 show that lycopene induces a specific artery-protecting effect by protecting LDL cholesterol against oxidation, thus decreasing the risk for coronary heart disease.

Lycopene was first made available in supplemental form because of a study showing that it might protect against the development of pancreatic cancer. Subsequent studies^445,446 have confirmed that low lycopene (and selenium) levels are present in pancreatic cancer patients compared to controls. Inflammation of the pancreas greatly increases the risk of pancreatic cancer and one study showed that patients with chronic pancreatitis⁵⁰³ had significantly lower plasma concentrations of antioxidants including selenium, vitamin A, vitamin E, beta-carotene and lycopene. This study was also omitted from the 512-page book.

Doctors are now evaluating the effects of lycopene in the treatment of many cancers. One study⁴³⁰ showed that a combination of lycopene and vitamin D3 was effective in inhibiting a promyelocytic leukemia cell line. The scientists conducting this study concluded that:

"The combination of low concentrations of lycopene with vitamin D3 exhibited a synergistic effect on cell proliferation and differentiation and an additive effect on cell cycle progression. Such synergistic antiproliferative and differentiating effects of lycopene and other compounds found in the diet and in plasma may suggest the inclusion of the carotenoid in the diet as a cancer-preventive measure."

At the April 12, 1999 meeting of the American Association of Cancer Research, a presentation was made showing that the administration of 15 mg twice a day of a lycopene supplement to prostate cancer patients for 30 days resulted in a 20% reduction in PSA and a shrinkage of tumor volume.

While the authors were bashing beta-carotene because it failed to prevent lung cancer in long-term smokers, they ignored another study⁴³⁴ showing that high serum levels of lycopene conferred a 44% risk reduction in lung cancer, whereas high serum levels of beta-carotene and other nutrients had no effect on lung cancer risk.

The sheer number of positive published studies linking lycopene and other carotenoids to lowered disease risks makes a persuasive case for taking carotenoid supplements if adequate amounts are not obtained from dietary sources. At the same time, it has to be recognized that the preponderance of the evidence indicates that beneficial effects are most likely to occur when a wide range of carotenoids are consumed, along with sufficient amounts of other antioxidants like vitamin E, C and selenium to maintain the stability of these carotenoids in the body.

Conclusions

As previously stated, the press release issued by the National Academy of Sciences used to promote the 512-page book said:

"Insufficient evidence exists to support claims that taking megadoses of dietary antioxidants, such as selenium and vitamins C and E, or carotenoids, including beta-carotene, can prevent chronic diseases."

This statement, however, is contradicted by published findings presented in the 512-page book itself showing disease risk reduction benefits to vitamin C, vitamin E, selenium and the carotenoids.

The 512-page book omitted many other positive published studies about these supplements. When these omissions are added to the favorable findings that were reported on in the book, it is difficult to ascertain how anyone concerned about protecting their health would not supplement with vitamin C, vitamin E, selenium and the carotenoids.

The media’s response to the press release promoting the book was to question the value of all dietary supplements. Yet the book did not review folic acid, coenzyme Q10, B-vitamins, zinc or a host of other dietary supplements commonly consumed. These nutrients have shown considerable disease risk reduction benefits in several thousand published studies.

The overriding question is, Does this 512-page book have any meaning to the vitamin consumer who takes many different nutrients? Our unequivocal answer is no!

The serious vitamin consumer takes high potencies of 50 to 90 nutrients every day. Many of these nutrients work synergistically together to protect against disease. For instance, coenzyme Q10 has been shown to protect LDL cholesterol against vitamin E by-product-induced peroxidation. This fact was first published in the National Academy of Sciences’ own journal (Proc Natl Acad Sci; 1991, USA 88:1646-1650), but omitted from the 512-page book published by the National Academy of Sciences. As reported in the April 2000 issue of Life Extension magazine (pages 21-22), the reason vitamin E appears to work so well in some studies, but fails in other studies, may relate to the amount of coenzyme Q10 naturally present in the bodies of test subjects. Coenzyme Q10 may act as a “silent partner” in amplifying the beneficial effects of vitamin E, whereas a CoQ10 deficit may enable vitamin E breakdown products to induce certain types of free radicals.

While the serious vitamin consumer long-ago recognized the importance of taking synergistic antioxidant therapies, mainstream scientists remain fixated in attempting to evaluate the effects of one nutrient at a time. While this research is helpful in identifying potential life extending supplements, it does not provide the information needed by those who consume multiple nutrients.

The fundamental problem with the National Academy of Sciences’ 512-page book is that it focused primarily on studies involving single nutrients, while the serious vitamin consumer is taking many nutrients concomitantly. The 512-page book failed to address the synergistic effects of taking multiple dietary supplements.

One of the more positive conclusions from the 512-page book was the recommendation for “full-scale intervention trials to test the preventive potential of vitamin C, vitamin E, selenium and the carotenoids for chronic disease.” While the authors allege there is “insufficient evidence” today, they acknowledge that the disease reducing potential of these nutrients should not be ignored.

This 512-page book was substantially funded by the U.S. Department of Health and Human Services, which oversees the Food and Drug Administration (FDA). The Canadian health ministry also provided funding. The FDA and Canadian health ministry have been historically biased against dietary supplements and may use this book to gain greater regulatory authority. As a propaganda tool, the book has been highly effective in persuading the media to generate anti-supplement reports worldwide.

The U.S. and Canadian governments spent considerable tax dollars funding this report that questions the value of vitamin C, vitamin E, selenium and the carotenoids. People who rely on the popular press and Federal government to inform them about health matters may be dissuaded from using dietary supplements based on the misleading press release used to promote the book.

For those who understand the premise behind using multiple supplements to statistically reduce the risk of degenerative disease, the book will serve as a reminder that the government is still committed to disseminating false and misleading information against dietary supplements. This misinformation campaign continues despite the existence of persuasive evidence that the proper use of these supplements could dramatically reduce the incidences of cardiovascular disease, cancer, dementia, cataract, immune dysfunction and a host of other diseases related to aging.

References

Kolonel LN, et al. Multiethnic studies of diet, nutrition, and cancer in Hawaii. Princess Takamatsu Symp 1985;16:29-40.
Verhoeven DT, et al. Vitamins C and E, retinol, beta-carotene and dietary fibre in relation to breast cancer risk: a prospective cohort study. Br J Cancer 1997;75(1):149-55.
Kurbacher CM, et al. Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro. Cancer Lett 1996 Jun 5;103(2):183-9.
Ramaswamy G, et al. Serum carotene, vitamin A, and vitamin C levels in breast cancer and cancer of the uterine cervix. Nutr Cancer 1996;25(2):173-7.
Guo WD, et al. Diet, serum markers and breast cancer mortality in China. Jpn J Cancer Res 1994 Jun;85(6):572-7.
Rohan TE, et al. Dietary factors and survival from breast cancer. Nutr Cancer 1993;20(2):167-77.
Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci U S A 1976 Oct;73(10):3685-9.
Venkatesan K, et al. Effect of ascorbic acid on blood levels of DDS. Lepr India 1979 Oct;51(4):511-4.
Fontana M . Vitamin C (ascorbic acid): clinical implications for oral health--a literature review. Compendium 1994 Jul;15(7):916, 918, 920 passim; quiz 930.
Aurer-Kozelj J, et al. The effect of ascorbic acid supplementation on periodontal tissue ultrastructure in subjects with progressive periodontitis. Int J Vitam Nutr Res 1982;52(3):333-41.
Trykowsky J, et al. [The use of toothpaste with vitamin C in treating periodontitis]. Stomatologiia (Mosk) 1994 Jan-Mar;73(1):11-3.
Holmes LG. Effects of smoking and/or vitamin C on crevicular fluid flow in clinically healthy gingiva. Quintessence Int 1990 Mar;21(3):191-5.
Muzzarelli R, et al. Reconstruction of parodontal tissue with chitosan. Biomaterials 1989 Nov;10(9):598-603.
Rubinoff AB, et al. Vitamin C and oral health. J Can Dent Assoc 1989 Sep;55(9):705-7.
Melnick SL, et al. A case-control study of plasma ascorbate and acute necrotizing ulcerative gingivitis. J Dent Res 1988 May;67(5):855-60.
Jacob RA, et al. Experimental vitamin C depletion and supplementation in young men. Nutrient interactions and dental health effects. Ann N Y Acad Sci 1987;498:333-46.
Leggott PJ, et al. The effect of controlled ascorbic acid depletion and supplementation on periodontal health. J Periodontol 1986 Aug;57(8):480-5.
Ellis CN, et al. Scurvy. A case caused by peculiar dietary habits. Arch Dermatol1984 Sep;120(9):1212-4.
Khan PK, et al. Vitamin C mediated amelioration of pesticide genotoxicity in murine spermatocytes. Cytobios 1994;80(323):199-204.
Sarma L, et al. Protective effects of vitamins C and E against gamma-ray-induced chromosomal damage in mouse. Int J Radiat Biol 1993 Jun;63(6):759-64.
21.Dreosti I, et al. Antioxidants and UV-induced genotoxicity. Res Commun Chem Pathol Pharmacol 1992 Feb;75(2):251-4.
Trizna Z, et al. Effects of N-acetyl-L-cysteine and ascorbic acid on mutagen-induced chromosomal sensitivity in patients with head and neck cancers. Am J Surg 1991 Oct;162(4):294-8.
Pohl H, et al. Vitamin C intake influences the bleomycin-induced chromosome damage assay: implications for detection of cancer susceptibility and chromosome breakage syndromes. Mutat Res 1989 Oct;224(2):247-52.
Pohl H, et al. Vitamin C intake influences the bleomycin-induced chromosome damage assay: implications for detection of cancer susceptibility and chromosome breakage syndromes. 1989 Mutat Res Oct;224(2):247-52.
Gebhart E, et al. The action of anticlastogens in human lymphocyte cultures and their modification by rat-liver S9 mix. II. Studies with vitamins C and E. Mutat Res 1985 Mar;149(1):83-94.
Antunes LM, et al. Effects of high doses of vitamins C and E against doxorubicin-induced chromosomal damage in Wistar rat bone marrow cells. Mutat Res 1998 Nov 9;419(1-3):137-43.
Tavares DC, et al. Protective effects of the amino acid glutamine and of ascorbic acid against chromosomal damage induced by doxorubicin in mammalian cells. Teratog Carcinog Mutagen 1998;18(4):153-61.
Cozzi R, et al. Ascorbic acid and beta-carotene as modulators of oxidative damage. Carcinogenesis 1997 Jan;18(1):223-8.
Makedonov GP, et al. [The anticlastogenic effect of ascorbic acid in relation to the damages inducedin human lymphocytes by the photomutagenic action of 8-methoxypsoralen and by ammonium molybdate]. Radiats Biol Radioecol 1995 Sep-Oct;35(5):726-9.
Makedonov GP, et al. [The anticlastogenic effect of ascorbic acid in relation to the damages induced in human lymphocytes by the photomutagenic action of 8-methoxypsoralen and by ammonium molybdate]. [Article in Russian] Radiats Biol Radioecol 1995 Sep-Oct;35(5):726-9.
31.Anderson D, et al. The effect of antioxidants on bleomycin treatment in in vitro and in vivo genotoxicity assays. Mutat Res 1995 Jun;329(1):37-47.
Piyathilake CJ, et al. Cigarette smoking, intracellular vitamin deficiency, and occurrence of micronuclei in epithelial cells of the buccal mucosa. Cancer Epidemiol Biomarkers Prev 1995 Oct-Nov;4(7):751-8.
Bilgrami KS, et al. Cumulative effect of T-2 toxin and vitamin C on chromosomal abnormalities in the bone marrow cells of mice (Mus musculus). Cytobios 1995;81(326):171-4.
Antunes LM, et al. Protection and induction of chromosomal damage by vitamin C in human lymphocyte cultures. Teratog Carcinog Mutagen 1999;19(1):53-9.
Konturek PC, et al. Helicobacter pylori associated gastric pathology. J Physiol Pharmacol 1999 Dec;50(5):695-710.
Bennedsen M, et al. Treatment of H. pylori infected mice with antioxidant astaxanthin reduces gastric inflammation, bacterial load and modulates cytokine release by splenocytes. Immunol Lett 1999 Dec 1;70(3):185-9.
Fraser AG, et al. Gastric juice ascorbic acid is related to Helicobacter pylori infection but not ethnicity.J Gastroenterol Hepatol 1999 Nov;14(11):1070-3.
Rokkas T, et al. Relationship of Helicobacter pylori CagA(+) status to gastric juice vitamin C levels. Eur J Clin Invest 1999 Jan;29(1):56-62.
Jarosz M, et al. Effects of high dose vitamin C treatment on Helicobacter pylori infection and total vitamin C concentration in gastric juice. Eur J Cancer Prev 1998 Dec;7(6):449-54.
Zhang ZW, et al. The relation between gastric vitamin C concentrations, mucosal histology, and CagA seropositivity in the human stomach. Gut 1998 Sep;43(3):322-6.
Drake IM, et al. Ascorbic acid may protect against human gastric cancer byscavenging mucosal oxygen radicals. Carcinogenesis 1996 Mar;17(3):559-62.
Retsky KL, et al. Vitamin C prevents metal ion-dependent initiation and propagation of lipid peroxidation in human low-density lipoprotein. Biochim Biophys Acta 1995 Aug 3;1257(3):279-87.
Scaccini C, et al. A critical assessment of the effects of aminoguanidine and ascorbate on the oxidative modification of LDL: evidence for interference with some assays of lipoprotein oxidation by aminoguanidine.J Lipid Res 1994 Jun;35(6):1085-92.
Scaccini C, et al. A critical assessment of the effects of aminoguanidine and ascorbate on the oxidative modification of LDL: evidence for interference with some assays of lipoprotein oxidation by aminoguanidine. J Lipid Res 1994 Jun;35(6):1085-92.
Azenabor AA, et al. Generation of reactive oxygen species and formation and membrane lipid peroxides in cells infected with Chlamydia trachomatis. Int J Infect Dis 2000;4(1):46-50.
Shilotri PG, et al. Effect of mega doses of vitamin C on bactericidal ativity of leukocytes. Am J Clin Nutr 1977 Jul;30(7):1077-81.
Anderson R. Effects of ascorbate on normal and abnormal leucocyte functions. Nutr Res Suppl 1982;23:23-34.
Corberand J, et al. Malignant external otitis and polymorphonuclear leukocyte migration impairment. Improvement with ascorbic acid. Arch Otolaryngol 1982 Feb;108(2):122-4.
Anderson R, et al . Effects of ascorbate on leucocytes: Part III. In vitro and in vivo stimulation of abnormal neutrophil motility by ascorbate. Arch Otolaryngol 1982 Feb;108(2):122-4S Afr Med J 1979 Sep 8;56(11):429-33.
Boura P, et al . Monocyte locomotion in anergic chronic brucellosis patients: the in vivo effect of ascorbic acid. Immunopharmacol Immunotoxicol 1989;11(1):119-29.
Foster CS, et al. Ascorbate therapy in impaired neutrophil and monocyte chemotaxis. With atopy, hyperimmunoglobulinemia E, and recurrent infection. Arch Ophthalmol 1978 Nov;96(11):2069-72.
Rebora A, et al. Repeated staphylococcal pyoderma in two siblings with defective neutrophil bacterial killing. Dermatologica 1980;160(2):106-12.
Patrone F, et al. Disorders of neutrophil function in children with recurrent pyogenic infections. Med Microbiol Immunol (Berl) 1982;171(2):113-22.
Patrone F, et al. Effects of ascorbic acid on neutrophil function. Studies on normal and chronic granulomatous disease neutrophils. Acta Vitaminol Enzymol 1982;4(1-2):163-8.
Rebora A, et al. Neutrophil dysfunction and repeated infections: influence of levamisole and ascorbic acid. Br J Dermatol 1980 Jan;102(1):49-56.
de la Fuente M, et al. Immune function in aged women is improved by ingestion of vitamins C and E. Can J Physiol Pharmacol 1998 Apr;76(4):373-80.
Levy R, et al. Successful treatment of a patient with recurrent furunculosis by vitamin C: improvement of clinical course and of impaired neutrophil functions. Int J Dermatol 1993 Nov;32(11):832-4.
Anderson R. Ascorbate-mediated stimulation of neutrophil motility and lymphocyte transformation by inhibition of the peroxidase/H2O2/halide system in vitro and in vivo. Am J Clin Nutr 1981 Sep;34(9):1906-11.
Ferrandez MD, et al. Effects in vitro of several antioxidants on the natural killer function of aging mice. Exp Gerontol 1999 Aug;34(5):675-85.
Heuser G, et al. Enhancement of natural killer cell activity and T and B cell function by buffered vitamin C in patients exposed to toxic chemicals: the role of protein kinase-C. Immunopharmacol Immunotoxicol 1997 Aug;19(3):291-312.
Hurlimann R, et al. [Scurvy--a mistakenly forgotten disease]. [Article in German] Schweiz Med Wochenschr 1994 Aug 9;124(31-32):1373-80.
Ghorbani AJ, et al. Scurvy. J Am Acad Dermatol 1994 May;30(5 Pt 2):881-3.
Valkonen MM, et al. Vitamin C prevents the acute atherogenic effects of passive smoking. Free Radic Biol Med 2000 Feb 1;28(3):428-36.
Galley HF, et al. Combination oral antioxidant supplementation reduces blood pressure. Clin Sci (Colch) 1997 Apr;92(4):361-5.
Gokce N, et al.Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Circulation 1999 Jun 29;99(25):3234-40.
Chambers JC, et al.Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin c therapy. Circulation 1999 Mar 9;99(9):1156-60.
Wilkinson IB, Megson IL, et al. Oral vitamin C reduces arterial stiffness and platelet aggregation in humans. J Cardiovasc Pharmacol 1999 Nov;34(5):690-3.
Jeserich M, et al. Vitamin C improves endothelial function of epicardial coronary arteries in patients with hypercholesterolaemia or essential hypertension--assessed by cold pressor testing. Eur Heart J 1999 Nov;20(22):1676-80.
Frei B . On the role of vitamin C and other antioxidants in atherogenesis and vascular dysfunction. Proc Soc Exp Biol Med 1999 Dec;222(3):196-204.
Fuller CJ, et al. Effect of ascorbate supplementation on low density lipoprotein oxidation in smokers. Atherosclerosis 1996 Jan 26;119(2):139-50.
Kuusi T . Vitamin C prevents the acute atherogenic effects of passive smoking.Valkonen MM, Free Radic Biol Med 2000 Feb 1;28(3):428-36.
Zhang J, et al. A single high dose of vitamin C counteracts the acute negative effect on microcirculation induced by smoking a cigarette. Microvasc Res 1999 Nov;58(3):305-11.
Purkayastha SS, et al. Effect of vitamin C and E in modulating peripheral vascular response to local cold stimulus in man at high altitude. Jpn J Physiol 1999 Apr;49(2):159-67.
Chamiec T, et al.Effects of antioxidant vitamins C and E on signal-averaged electrocardiogram in acute myocardial infarction. Am J Cardiol 1996 Feb 1; 77(4):237-41.
Gatto LM, et al. Ascorbic acid induces a favorable lipoprotein profile in women. J Am Coll Nutr 1996 Apr;15(2):154-8.
Singh RB, et al . Usefulness of antioxidant vitamins in suspected acute myocardial infarction (the Indian experiment of infarct survival-3). Am J Cardiol 1996 Feb 1;77(4):232-6.
Munoz JA, et al . Effect of VITAMIN C on lipoproteins in healthy adults. Ann Med Interne (Paris) 1994;145(1):13-9.
Tomoda H, et al. Possible prevention of postangioplasty restenosis by Ascorbic acid. Am J Cardiol 1996 Dec 1;78(11):1284-6.
Laskowski H, et al. Mortality and clinical course of patients with acute myocardial infarction treated with streptokinase and antioxidants: mannitol and Ascorbic acid. Int J Cardiol 1995 Mar 3;48(3):235-7.
Eriksson J, et al. Magnesium and Ascorbic acid supplementation in diabetes mellitus. Ann Nutr Metab 1995;39(4):217-23.
Cerna O,et al.Plasma lipids, lipoproteins and atherogenic index in men and women administered vitamin c. Cor Vasa 1992;34(3):246-54.
Barta E, et al.Protective effect of alpha-tocopherol and L-ascorbic acid against the ischemic-reperfusion injury in patients during open-heart surgery. Bratisl Lek Listy 1991 Mar-Apr;92(3-4):174-83.
Salonen JT,et al. Effects of antioxidant supplementation on platelet function: a randomized pair-matched, placebo-controlled, double-blind trial in men with low antioxidant status. Am J Clin Nutr 1991 May;53(5):1222-9.
Mayer-Davis EJ, et al. Vitamin c intake and cardiovascular disease risk factors in persons with non-insulin-dependent diabetes mellitus. From the Insulin Resistanc Atherosclerosis Study and the San Luis Valley Diabetes Study. rev Med 1997 May-Jun;26(3):277-83.
Bostom AG, et al.The effect of high-dose ascorbate supplementation on plasma lipoprotein(a) levels in patients with premature coronary heart disease. Pharmacotherapy 1995 Jul-Aug;15(4):458-64.
Westhuyzen J, et al.Effect of preoperative supplementation with alpha-tocopherol and ascorbic acid on myocardial injury in patients undergoing cardiac operations. J Thorac Cardiovasc Surg 1997 May;113(5):942-8.
Tanaka H, et al.Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study. Arch Surg 2000 Mar;135(3):326-31.
Kodama N, et al. Cisternal irrigation therapy with urokinase and ascorbic acid for prevention of vasospasm after aneurysmal subarachnoid hemorrhage. Outcome in 217 patients. Surg Neurol 2000 Feb;53(2):110-7; discussion 117-8.
Sinclair S, et al. Male infertility: nutritional and environmental considerations. Altern Med Rev 2000 Feb;5(1):28-38.
van Rooij J, et al. Oral vitamins C and E as additional treatment in patients with acute anterior uveitis: a randomised double masked study in 145 patients. Br J Ophthalmol 1999 Nov;83(11):1277-82.
Zollinger PE, et al. Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures:a randomised trial. Lancet 1999 Dec 11;354 (9195):2025-8.
Gorton HC, et al. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections. J Manipulative Physiol Ther 1999 Oct;22(8):530-3.
Vermeer IT, et al. Effect of ascorbic acid and green tea on endogenous formation of N-nitrosodimethylamine and N-nitrosopiperidine in humans. Mutat Res 1999 Jul 16;428(1-2):353-61.
Reinhold U, et al. Treatment of progressive pigmented purpura with oral bioflavonoids and ascorbic acid: an open pilot study in 3 patients. J Am Acad Dermatol 1999 Aug;41(2 Pt 1):207-8.
Hemila H. Vitamin C supplementation and common cold symptoms: factors affecting the magnitude of the benefit. Med Hypotheses 1999 Feb;52(2):171-8.
McAuliffe AV, et al. Administration of ascorbic acid and an aldose reductase inhibitor (tolrestat) in diabetes: effect on urinary albumin excretion. Nephron 1998 Nov;80(3):277-84.
de la Fuente M, et al. Immune function in aged women is improved by ingestion of vitamins C and E. Can J Physiol Pharmacol 1998 Apr;76(4):373-80.
Allard JP, et al. Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects AIDS 1998 Sep 10;12(13):1653.
Eberlein-Konig B, et al. Phototoxic lysis of erythrocytes from humans is reduced after oral intake of Ascorbic acid and d-alpha-tocopherol. Photodermatol Photoimmunol Photomed 1997 Oct-Dec;13(5-6):173-7.
Alessio HM, et al.Exercise-induced oxidative stress before and after VITAMIN C supplementation. Int J Sport Nutr 1997 Mar;7(1):1-9.
Schwille PO, et al. Postprandial hyperinsulinaemia, insulin resistance and inappropriately high phosphaturia are features of younger males with idiopathic calcium urolithiasis: attenuation by Ascorbic acid supplementation of a test meal. Urol Res 1997;25(1):49-58.
Hemila H, et al. Vitamin C intake and susceptibility to the common cold. Br J Nutr 1997 Jan;77(1):59-72.
Gustafsson U, et al. The effect of VITAMIN C in high doses on plasma and biliary lipid composition in patients with cholesterol gallstones: prolongation of the nucleation time. Eur J Clin Invest 1997 May;27(5):387-91.
Jeng KC, et al.Supplementation with vitamins C and E enhances cytokine production by peripheral blood mononuclear cells in healthy adults. Am J Clin Nutr 1996 Dec;64(6):960-5.
McAlindon ME, et al. Effect of allopurinol, sulphasalazine, and VITAMIN C on aspirin induced gastroduodenal injury in human volunteers. Gut 1996 Apr;38(4):518-24.
Boffa MJ, et al. A double-blind, placebo-controlled, crossover trial of oral VITAMIN C in erythropoietic protoporphyria. Photodermatol Photoimmunol Photomed 1996 Feb;12(1):27-30.
Lonnrot K, et al. The effect of ascorbate and ubiquinone supplementation on plasma and CSF total antioxidant capacity. Free Radic Biol Med 1996;21(2):211-7.
Nadgrodkiewicz K , et al. [The effect of intravenous Ascorbic acid on urinary 17-hydroxysteroid excretion at an early stage of cerebral stroke]. Neurol Neurochir Pol 1996 Jan-Feb;30(1):49-56.
Wang H, et al. Experimental and clinical studies on the reduction of erythrocyte sorbitol-glucose ratios by Ascorbic acid in diabetes mellitus. Diabetes Res Clin Pract 1995 Apr;28(1):1-8.
Sharma DC, et al. .Correction of anemia and iron deficiency in vegetarians by administration of Ascorbic acid. Indian J Physiol Pharmacol 1995 Oct;39(4):403-6.
Paolisso G, et al. Metabolic benefits deriving from chronic VITAMIN C supplementation in aged non-insulin dependent diabetics. J Am Coll Nutr 1995 Aug;14(4):387-92.
Gastaldello K,et al.Resistance to erythropoietin in iron-overloaded haemodialysis patients can be overcome by Ascorbic acid administration. Nephrol Dial Transplant 1995;10 Suppl 6:44-7.
Skin wound healing process. A double-blind, prospective and randomized trial. Eur Surg Res 1995;27(3):158-66.
Wang H, Zhang ZB, et al. [Reduction of erythrocyte sorbitol by Ascorbic acid in patients with diabetes mellitus]. Chung Hua I Hsueh Tsa Chih 1994 Sep;74(9):548-51, 583.
Herbaczynska-Cedro K, et al. Inhibitory effect of vitamins C and E on the oxygen free radical production in human polymorphonuclear leucocytes. Eur J Clin Invest 1994 May;24(5):316-9.
Cunningham JJ, et al. VITAMIN C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent diabetes mellitus. J Am Coll Nutr 1994 Aug;13(4):344-50.
Kataoka A, et al. [Intermittent high-dose VITAMIN C therapy in patients with HTLV-I-associated myelopathy]. Rinsho Shinkeigaku 1993 Mar;33(3):282-8.
Dumitrescu C, et al. Effect of VITAMIN C administration on the ratio between the pro- and antioxidative factors. Rom J Endocrinol 1993;31(1-2):81-4.
Karduss Urueta A, et al. [Results of the treatment of chronic idiopathic thrombocytopenic purpura with Ascorbic acid]. Gac Med Mex 1993 Jan-Feb;129(1):23-5.
Dawson EB, et al. Effect of Ascorbic acid supplementation on the sperm quality of smokers. Fertil Steril 1992 Nov;58(5):1034-9.
Triana Mantilla ME, et al. [The effect of VITAMIN C on the lipolytic activity in type-II diabetics with angiopathy]. [Article in Spanish] Angiologia 1991 Mar-Apr;43(2):77-81.
Reed PI, et al.Effect of Ascorbic acid on the intragastric environment in patients at increased risk of developing gastric cancer. IARC Sci Publ 1991;(105):139-42.
Beser E et al.The effects of short-term VITAMIN C on plasma bun, uric acid, cholesterol and triglyceride levels. Acta Med Hung 1991;48(1-2):73-8.
Bucca C, et al. Effect of VITAMIN C on histamine bronchial responsiveness of patients with allergic rhinitis. Ann Allergy 1990 Oct;65(4):311-4 Ann Allergy 1990 Oct;65(4):311-4.
Hunt JR, et al. Ascorbic acid: effect on ongoing iron absorption and status in iron-depleted young women. Am J Clin Nutr 1990 Apr;51(4):649-55.
Mai J, et al. High dose antioxidant supplementation to MS patients. Effects on glutathione peroxidase, clinical safety, and absorption of selenium. Biol Trace Elem Res 1990 Feb;24(2):109-17.
Mirvish SS, et al. Effect of ascorbic acid dose taken with a meal on nitrosoproline excretion in subjects ingesting nitrate and proline. Nutr Cancer 1998;31(2):106-10.
Seven A, et al. Biochemical evaluation of oxidative stress in propylthiouracil treated hyperthyroid patients. Effects of vitamin C supplementation. Clin Chem Lab Med 1998 Oct;36(10):767-70.
129.Heuser G, et al. Enhancement of natural killer cell activity and T and B cell function by buffered VITAMIN C in patients exposed to toxic chemicals: the role of protein kinase-C. Immunopharmacol Immunotoxicol 1997 Aug;19(3):291-312.
Liyanage C, et al. Iron absorption from a traditional Sri Lankan weaning food and the enhancing effect of Ascorbic acid in adult male volunteers. Ceylon Med J 1996 Dec;41(4):135-40.
Hunt C, et al. The clinical effects of VITAMIN Csupplementation in elderly hospitalised patients with acute respiratory infections. Int J Vitam Nutr Res 1994;64(3):212-9.
Johnston CS, et al. Megadose of VITAMIN C delays insulin response to a glucose challenge in normoglycemic adults. Am J Clin Nutr 1994 Nov;60(5):735-8.
Bednar C, et al. Nitrate and VITAMIN C from fruits and vegetables: impact of intake variations on nitrate and nitrite excretions of humans. Plant Foods Hum Nutr 1994 Jan;45(1):71-80.
Levin ED, et al. Clinical trials using Ascorbic acid aerosol to aid smoking cessation. Drug Alcohol Depend 1993 Oct;33(3):211-23.
135.Maxwell SR, et al. Changes in plasma antioxidant status during eccentric exercise and the effect of vitamin supplementation. Free Radic Res Commun 1993;19(3):191-202 .
Shah GM, et al. Effects of Ascorbic acid and pyridoxine supplementation on oxalate metabolism in peritoneal dialysis patients. Am J Kidney Dis 1992 Jul;20(1):42-9.
Niki E. Interaction of ascorbate and alpha-tocopherol. Ann N Y Acad Sci 1987;498:186-99.
Chan AC, et al. Partners in defense, vitamin E and vitamin C. Can J Physiol Pharmacol 1993 Sep;71(9):725-31.
Bielory L, et al. Asthma and vitamin C. Ann Allergy 1994 Aug;73(2):89-96; quiz 96-100.
Hunt C, et al. The clinical effects of vitamin C supplementation in elderly hospitalized patients with acute respiratory infections. Int J Vitam Nutr Res 1994;64(3):212-9.
141.Nowak D, et al. Effect of ascorbic acid on hydroxyl radical generation by chemical, enzymatic and cellular systems. Importance for antioxidant prevention of pulmonary emphysema. Biomed Biochim Acta 1991;50(3):265-72.
142.Yu AB, et al.Oxidation kinetics of an antiasthmatic, 2-[(4-hydroxyphenyl)amino]-5-methoxybenzenemethanol, and stabilization with ascorbic acid. J Pharm Sci 1990 Oct;79(10):913-5.
Anderson R, et al. Ascorbic acid in bronchial asthma. S Afr Med J 1983 Apr 23;63(17):649-52.
Mohsenin V, et al. Effect of ascorbic acid on response to methacholine challenge in asthmatic subjects. Am Rev Respir Dis 1983 Feb;127(2):143-7.
Miric M, et al. [Effect of vitamin C on exercise-induced bronchoconstriction]. [Article in Serbo-Croatian (Roman)] Plucne Bolesti 1991 Jan-Jun;43(1-2):94-7.
Anderson R, et al. The effect of ascorbate on cellular humoral immunity in asthmatic children. S Afr Med J 1980 Dec 13;58(24):974-7.
Anah CO, et al. High dose ascorbic acid in Nigerian asthmatics. Trop Geogr Med 1980 Jun;32(2):132-7.
Paleologos M, et al. Cohort study of vitamin C intake and cognitive impairment. Am J Epidemiol 1998 Jul 1;148(1):45-50.
Lenton KJ, et al. Direct correlation of glutathione and ascorbate and their dependence on age and season in human lymphocytes. Am J Clin Nutr 2000 May;71(5):1194-200.
Jain A, et al. Effect of ascorbate or N-acetylcysteine treatment in a patient with hereditary glutathione synthetase deficiency. J Pediatr 1994 Feb;124(2):229-33.
151.Dubey SS, et al. Ascorbic acid, dehydroascorbic acid and glutathione in liver disease. Indian J Physiol Pharmacol 1987 Oct-Dec;31(4):279-83.
Gorton HC, et al. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections. J Manipulative Physiol Ther 1999 Oct;22(8):530-3.
Hemila H, et al. Vitamin C and acute respiratory infections. Int J Tuberc Lung Dis 1999 Sep;3(9):756-61 Int J Tuberc Lung Dis 1999 Sep;3(9):756-61.
154.Gonul B, et al. Effects of vitamin C supplementation on plasma antioxidant status in unfed periods. Gen Pharmacol 1999 Feb;32(2):195-9.
Negre-Salvayre A, et al. alpha-Tocopherol, ascorbic acid, and rutin inhibit synergistically the copper-promoted LDL oxidation and the cytotoxicity of oxidized LDL to cultured endothelial cells. Biol Trace Elem Res 1995 Jan-Mar;47(1-3):81-91.
Harwood HJ Jr, et al. Inhibition of human leukocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase activity by ascorbic acid. An effect mediated by the free radical monodehydroascorbate. J Biol Chem 1986 Jun 5;261(16):7127-35.
Panda K, et al. Vitamin C prevents cigarette smoke induced oxidative damage of proteins and increased proteolysis. Free Radic Biol Med 1999 Nov;27(9-10):1064-79.
Lee BM, et al. Inhibition of oxidative DNA damage, 8-OHdG, and carbonyl contents in smokers treated with antioxidants (vitamin E, vitamin C, beta-carotene and red ginseng). Cancer Lett 1998 Oct 23;132(1-2):219-27.
Helen A, et al. Vitamin C supplementation on hepatic oxidative stress induced by cigarette smoke. J Appl Toxicol 1997 Sep-Oct;17(5):289-95.
Menzel DB Antioxidant vitamins and prevention of lung disease. Ann N Y Acad Sci 1992 Sep 30;669:141-55.
Banic S. Immunostimulation by vitamin C. Int J Vitam Nutr Res Suppl 1982;23:49-52.
Beyer RE The role of ascorbate in antioxidant protection of biomembranes: interaction with vitamin E and coenzyme Q. J Bioenerg Biomembr 1994 Aug;26(4):349-58.
Kromhout D, et al.Saturated fat, vitamin C and smoking predict long-term population all-cause mortality rates in the Seven Countries Study. Int J Epidemiol 2000 Apr;29(2):260-5.
Houston DK, et al. Does vitamin C intake protect against lead toxicity? Nutr Rev 2000 Mar;58(3 Pt 1):73-5.
Douglas RM, et al. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2000;2:CD000980.
Young VR. Evidence for a recommended dietary allowance for vitamin C from pharmacokinetics: a comment and analysis. Proc Natl Acad Sci U S A 1996 Dec 10;93(25):14344-.
Salonen JT. Selenium in ischaemic heart disease. Int J Epidemiol, 1987 Jun, 16:2, 323-8.
Paolisso G, et al. Primary and secondary prevention of atherosclerosis: is there a role for antioxidants? Diabetes Metab, 1999 Sep, 25:4, 298-306.
Hercberg S, et al. "The SU.VI.MAX Study": a primary prevention trial using nutritional doses of antioxidant vitamins and minerals in cardiovascular diseases and cancers. SUpplementation on VItamines et Minéraux AntioXydants. Food Chem Toxicol, 1999 Sep, 37:9-10, 925-30.
Paolisso G, et al. Primary and secondary prevention of atherosclerosis: is there a role for antioxidants? Diabetes Metab 1999 Sep;25(4):298-306.
Neve J. Selenium and cardiovascular pathology. Source Pathol Biol (Paris), 1989 Dec, 37:10, 1102-6.
Dubois F, et al. [Selenium: physiologic role and value in human pathology]Pathol Biol (Paris), 1988 Oct, 36:8, 1017-25.
Virtamo J, et al. Serum selenium and the risk of coronary heart disease and stroke. Source Am J Epidemiol, 1985 Aug, 122:2, 276-82.
Kok FJ, et al. Selenium status and chronic disease mortality: Dutch epidemiological findings. Int J Epidemiol, 1987 Jun, 16:2, 329-32.
Ringstad J, et al. The TromsI Heart Study: serum selenium in a low-risk population for cardiovascular disease and cancer and matched controls. Ann Clin Res, 1987, 19:5, 351-4.
Berr C, et al. Demographic and cardiovascular risk factors in relation to antioxidant status: the EVA Study. Int J Vitam Nutr Res, 1998, 68:1, 26-35.
Jackson ML. Selenium: geochemical distribution and associations with human heart and cancer death rates and longevity in China and the United States. Biol Trace Elem Res, 1988 Jan, 15:, 13-21.
van de Vijver LP, et al. Lipoprotein oxidation, antioxidants and cardiovascular risk: epidemiologic evidence. Prostaglandins Leukot Essent Fatty Acids, 1997 Oct, 57:4-5, 479-87.
Crary EJ, et al. Potential clinical applications for high-dose nutritional antioxidants. Med Hypotheses, 1984 Jan, 13:1, 77-98.
Suadicani P, et al. Serum selenium concentration and risk of ischaemic heart disease in a prospective cohort study of 3000 males. Atherosclerosis, 1992 Sep, 96:1, 33-42.
Barceloux DG. Selenium. J Toxicol Clin Toxicol, 1999, 37:2, 145-72.
Huttunen JK. Selenium and cardiovascular diseases--an update. Biomed Environ Sci, 1997 Sep, 10:2-3, 220-6.
Neve J. Selenium and cardiovascular pathology. Pathol Biol (Paris), 1989 Dec, 37:10, 1102-6.
Kardinaal AF, et al. Association between beta-carotene and acute myocardial infarction depends on polyunsaturated fatty acid status. The EURAMIC Study. European Study on Antioxidants, Myocardial Infarction, and Cancer of the Breast. Arterioscler Thromb Vasc Biol, 1995 Jun, 15:6, 726-32.
van Poppel G, et al. Antioxidants and coronary heart disease. Ann Med, 1994 Dec, 26:6, 429-34.
Vitoux D, et al. Selenium, glutathione peroxidase, peroxides and platelet functions. Ann Biol Clin (Paris), 1996, 54:5, 181-7.
Nève J . Selenium as a risk factor for cardiovascular diseases. J Cardiovasc Risk, 1996 Feb, 3:1, 42-7.
Odeh RM, et al. Natural antioxidants for the prevention of atherosclerosis. Pharmacotherapy, 1995 Sep, 15:5, 648-59.
Ginter E. Nutrition in the prevention of ischemic heart disease Bratisl Lek Listy, 1989 Mar, 90:3, 203-21.
Kendler BS. Recent nutritional approaches to the prevention and therapy of cardiovascular disease. Prog Cardiovasc Nurs, 1997 Sum, 12:3, 3-23.
Dworkin BM. Selenium deficiency in HIV infection and the acquired immunodeficiency syndrome (AIDS). Chem Biol Interact, 1994 Jun, 91:2-3, 181-6.
Virtamo J. Serum selenium and the risk of coronary heart disease and stroke. Am J Epidemiol, 1985 Aug, 122:2, 276-82.
Kok FJ, et al. Selenium status and chronic disease mortality: Dutch epidemiological findings. Int J Epidemiol, 1987 Jun, 16:2, 329-32.
Ellis NI, et al. Selenium and vitamin E in relation to risk factors for coronary heart disease. J Clin Pathol, 1984 Feb, 37:2, 200-6.
Huttunen JK . Selenium and cardiovascular diseases--an update. Biomed Environ Sci, 1997 Sep, 10:2-3, 220-6.
Coudray C, et al. Lipid peroxidation level and antioxidant micronutrient status in a pre-aging population; correlation with chronic disease prevalence in a French epidemiological study (Nantes, France). J Am Coll Nutr, 1997 Dec, 16:6, 584-91.
Lush DT. Preventing heart disease and cancer. What randomized, primary-prevention studies show. Postgrad Med 1999 Oct 15;106(5):143-8.
Yu SY, et al. Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. Biol Trace Elem Res 1997 Jan;56(1):117-24.
Taylor EW, et al. Genomic structures of viral agents in relation to the biosynthesis of selenoproteins. Biol Trace Elem Res, 1997 Jan, 56:1, 63-91.
Zhang W, et al. Hepatitis C virus encodes a selenium-dependent glutathione peroxidase gene. Implications for oxidative stress as a risk factor in progression to hepatocellular carcinoma. Source Med Klin, 1999 Oct, 94 Suppl 3:, 2-6.
Peterhans E. Reactive oxygen species and nitric oxide in viral diseases. Biol Trace Elem Res, 1997 Jan, 56:1, 107-16.
Beck MA, et al. Dietary oxidative stress and the potentiation of viral infection. Annu Rev Nutr, 1998, 18:, 93-116.
Look MP, et al. Interferon/antioxidant combination therapy for chronic hepatitis C--a controlled pilot trial. Antiviral Res, 1999 Sep, 43:2, 113-22.
Seitz HK, et al. Alcohol and cancer. Recent Dev Alcohol, 1998, 14:, 67-95.
Zhang W, et al. Selenium-dependent glutathione peroxidase modules encoded by RNA viruses. Biol Trace Elem Res 1999 Nov;70(2):97-116.
Chemoprevention trial of human hepatitis with selenium supplementation in China. Biol Trace Elem Res 1989 Apr-May;20(1-2):15-22.
Campa A, et al. Mortality risk in selenium-deficient HIV-positive children. J Acquir Immune Defic Syndr Hum Retrovirol, 1999 Apr, 20:5, 508-13.
Campa A, et al. Mortality risk in selenium-deficient HIV-positive children. J Acquir Immune Defic Syndr Hum Retrovirol 1999 Apr 15;20(5):508-13.
Baum MK, et al. High risk of HIV-related mortality is associated with selenium deficiency. J Acquir Immune Defic Syndr Hum Retrovirol 1997 Aug.
Baum MK, et al. Micronutrient status in relationship to mortality in HIV-1 disease. Nutr Rev 1998 Jan;56(1 Pt 2):S135-9.
Look MP, et al. Serum selenium, plasma glutathione (GSH) and erythrocyte glutathione peroxidase (GSH-Px)-levels in asymptomatic versus symptomatic human immunodeficiency virus-1 (HIV-1)-infection. Eur J Clin Nutr. 1997 Apr;51(4):266-72.
Periquet BA, et al. Micronutrient levels in HIV-1-infected children. AIDS, 1995 Aug, 9:8, 887-93.
Hori K, et al. Selenium supplementation suppresses tumor necrosis factor alpha-induced human immunodeficiency virus type 1 replication in vitro. AIDS Res Hum Retroviruses, 1997 Oct, 13:15, 1325-32.
McCarty MF. natural antimutagenic agents may prolong efficacy of human immunodeficiency virus drug therapy. Med Hypotheses, 1997 Mar, 48:3, 215-20.
Cirelli A, et al. Serum selenium concentration and disease progress in patients with HIV infection. Clin Biochem, 1991 Apr, 24:2, 211-4.
Look MP, et al. Serum selenium, plasma glutathione (GSH) and erythrocyte glutathione peroxidase (GSH-Px)-levels in asymptomatic versus symptomatic human immunodeficiency virus-1 (HIV-1)-infection. Eur J Clin Nutr, 1997 Apr, 51:4, 266-72.
Constans J, et al. Selenium and HIV infection [editorial] Nutrition, 1999 Sep, 15:9, 719-20.
Olmsted L, et al. Selenium supplementation of symptomatic human immunodeficiency virus infected patients. Biol Trace Elem Res, 1989 Apr, 20:1-2, 59-65.
Taylor EW, et al. Genomic structures of viral agents in relation to the biosynthesis of selenoproteins. Biol Trace Elem Res, 1997 Jan, 56:1, 63-91.
Sappey C, et al. Vitamin, trace element and peroxide status in HIV seropositive patients: asymptomatic patients present a severe beta-carotene deficiency. Clin Chim Acta 1994 Oct 14;230(1):35-42.
Patrick L. Nutrients and HIV: part two--vitamins A and E, zinc, B-vitamins, and magnesium. Altern Med Rev 2000 Feb;5(1):39-51.
Constans J, et al. Selenium and HIV infection. Nutrition 1999 Sep;15(9):719-20.
May SW, et al. Selenium-based antihypertensives. Rationale and potential. Drugs 1998 Dec;56(6):959-64.
Rabaud C, et al. [Free radicals and HIV infection]. Ann Biol Clin (Paris) 1997 Nov-Dec;55(6):565-71.
Brown NA, et al. Nutrition supplements and the eye. Eye 1998;12 ( Pt 1):127-33.
Sperduto RD, et al. The Linxian cataract studies. Two nutrition intervention trials. Arch Ophthalmol 1993 Sep;111(9):1246-53.
Knekt P, et al. Serum antioxidant vitamins and risk of cataract. BMJ 1992 Dec 5;305(6866):1392-4.
Remarkable success of antioxidant treatment (selenomethionine and vitamin E) to a 34-year old patient with posterior subcapsular cataract, keratoconus, severe atopic eczema and asthma. Acta Ophthalmol (Copenh), 1988 Apr, 66:2, 237-8.
Karaküçük S, et al. Selenium concentrations in serum, lens and aqueous humour of patients with senile cataract. Acta Ophthalmol Scand, 1995 Aug, 73:4, 329-32.
Taylor A. Associations between nutrition and cataract. Nutr Rev, 1989 Aug, 47:8, 225-34.
Sperduto RD, et al. The Linxian cataract studies. Two nutrition intervention trials. Arch Ophthalmol, 1993 Sep, 111:9, 1246-53.
Christen WG, et al. Design of Physicians' Health Study II--a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. Ann Epidemiol 2000 Feb;10(2):125-3.
Orhan H, et al. Effects of some probable antioxidants on selenite-induced cataract formation and oxidative stress-related parameters in rats. Toxicology 1999 Dec 6;139(3):219-32.
Sperduto RD, et al. The Linxian cataract studies. Two nutrition intervention trials. Arch Ophthalmol 1993 Sep;111(9):1246-53.
Helmy M.H, et al. Effect of selenium supplementation on the activities of glutathione metabolizing enzymes in human hepatoma Hep G2 cell line. Toxicology (Ireland) 03 APR 2000, 144/1-3 (57-61).
Zimmermann M.B, et al. Effect of oral iodized oil on thyroid size and thyroid hormone metabolism in children with concurrent selenium and iodine deficiency European Journal of Clinical Nutrition (United Kingdom) 2000, 54/3 (209-213).
Reimund J.-M., Antioxidant and immune status in active Crohn's disease. A possible relationship. Clinical Nutrition (UK) 2000, 19/1 (43-48).
Alfthan G, et al. Selenium supplementation of children in a selenium-deficient area in China: Blood selenium levels and glutathione peroxidase activities. Biological Trace Element Research 2000, 73/2 (113-125).
Kiremidjian-Schumacher L, et al. Selenium and immunocompetence in patients with head and neck cancer. Biological Trace Element Research 2000, 73/2 (97-111).
Hatanaka N, et al. Selenium kinetics and changes in glutathione peroxidase activities in patients receiving long-term parenteral nutrition and effects of supplementation with selenite Nutrition 2000, 16/1 (22-26).
Byers T. What can randomized controlled trial tell us about nutrition and cancer prevention? Cancer Journal for Clinicians 1999, 49/6 (353-361).
Reimund J.-M, et al. Chronic radiation enteritis: The importance of selenium monitoring Nutrition Clinique et Metabolisme ( NUTR. CLIN. METAB.) (France) 1999, 13/2 (99-104).
Chandra R.K. Symposium on 'nutrition, infection and immunity' - Nutrition and immunology: From the clinic to cellular biology and back again. Proceedings of the Nutrition Society 1999, 58/3 (681-683).
Richard M.-J, et al. Micronutrients and ageing: Intakes and requirements Proceedings of the Nutrition Society (United Kingdom ) 1999, 58/3 (573-578).
Forceville X, et al. Selenium and sepsis. Nutrition Clinique et Metabolisme (France) 1999, 13/3 (177-186).
Kuroki F, et al. Selenium deficiency in Crohn's disease on long-term enteral nutrition: Report of a case. Kawasaki Medical Journal (Japan) 1999, 25/1 (23-27).
Racek J, et al. The influence of supplementation with vitamins and trace elements on markers of antioxidative defence in patients with rheumatic diseases. Klinicka Biochemie a Metabolismus (CzechRepublic) 1999, 7/4 (239-242).
Lasch K, et al. Selenium in therapy of colorectal cancer? Medizinische Klinik (Germany) 15 OCT 1999, 94/SUPPL. 3 (97-100).
Head K.A. Natural therapies for ocular disorders, Part one: Diseases of the retina Alternative Medicine Review 1999, 4/5 (342-359).
Geelhoed G.W. Metabolic maladaptation: Individual and social consequences of medical intervention in correcting endemic hypothyroidism. Nutrition 1999, 15/11-12 (908-932).
Duffield A.J., et al. An estimation of selenium requirements for New Zealanders American Journal of Clinical Nutrition 1999, 70/5 (896-903).
Prasad K.N, et al. Multiple antioxidants in the prevention and treatment of Parkinson's disease. Journal of the American College of Nutrition 1999, 18/5 (413-423).
Angstwurm M.W.A, et al. Selenium replacement in patients with severe systemic inflammatory response syndrome improves clinical outcome. Critical Care Medicine 1999, 27/9(1807-1813).
Caspi O, et al. Parkinson's disease: "Don't become your disease!" Integrative Medicine 1999, 2/1 (37-42).
Geerling B.J., et al. Nutrition and inflammatory bowel disease: An update Scandinavian Journal of Gastroenterology, Norway) 1999, 33/230 (95-105).
Metnitz P.G.H., et al. Antioxidant status in patients with acute respiratory distress syndrome. Intensive Care Medicine (Germany) 1999, 25/2 (180-185).
Zima T, et al. Trace elements in end-stage renal disease. Blood Purification (Switzerland) 1999, 17/4 (187-198).
Bowrey D.J., et al. Selenium deficiency and chronic pancreatitis: Disease mechanism and potential for therapy HPB Surgery (United Kingdom) 1999, 11/4 (207-216).
De Munck-Khoe L.K., et al.Micronutrients are synergists, not solo performers. Effectivity of food supplements. Pharmaceutisch Weekblad (Netherlands) 06 AUG 1999, 134/31 (1034-1039).
Allan C.B., et al. Responsiveness of selenoproteins to dietary selenium. Annual Review of Nutrition (United States) 1999, 19/- (1-16).
Pfeiffer J.M., et al. Effect of antioxidant supplementation on urine and blood markers of oxidative stress during extended moderate-altitude training Wilderness and Environmental Medicine (United States) 1999, 10/2 (66-74).
Perrone L, et al. Long-term zinc and iron supplementation in children of short stature: Effect of growth and on trace element content in tissues Journal of Trace Elements in Medicine and Biology (Germany) 1999, 13/1-2 (51-56).
Horvathova M, et al. Effect of selenium supplementation in asthmatic subjects on the expression of endothelial cell adhesion molecules in culture. Biological Trace Element Research 1999, 69/1 (15-26).
Meletis C.D., et al. Natural medicine approaches for the treatment of degenerative arthritis. Alternative and Complementary Therapies 1999, 5/3 (136-139).
Young K.J., et al. Intervention studies on cancer. European Journal of Cancer Prevention 1999, 8/2 (91-103).
Nelson M.A., et al. Selenium and prostate cancer prevention Seminars in Urologic Oncology 1999, 17/2 (91-96).
Hermus R.J., et al. Clinical importance of extra vitamins from supplements and enriched foodstuffs. Nederlands Tijdschrift voor Geneeskunde 24 APR 1999, 143/17 (889-893).
Girodon F., et al. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: A randomized controlled trial. Archives of Internal Medicine 12APR 1999, 159/7 (748-754).
Jochum F, et al. Is there any health risk of low dietary selenium supply in PKU-children. Nutrition Research 1999, 19/3 (349-360).
Verdoy J, et al. Selenium and infant nutrition: A review. Acta Pediatrica Espanola 1999, 57/1 (3-11).
Maskell C, et al. Dietary intake after pancreatectomy. British Journal of Surgery 1999, 86/3 (323-326).
Backovic D, et al. Environmental factors, health-related habits, and serum selenium levels in cancer patients and healthy controls. Biological Trace Element Research 1999, 67/1 (55-62).
Dodge M.L., et al. Selenium supplementation increases the polyunsaturated fatty acid content of human breast milk . Journal of Trace Elements in Experimental Medicine 1999, 12/1 (37-44).
Jiang C, et al. Selenium-induced inhibition of angiogenesis in mammary cancer at chemopreventive levels of intake. Mol Carcinog 1999 Dec;26(4):213-25.
Funke AM. [Potential of selenium in gynecologic oncology]. Med Klin 1999 Oct 15;94 Suppl 3:42-4.
[Role of sodium selenite as an adjuvant in radiotherapy of rectal carcinoma]. [Article in German] Med Klin 1997 Sep 15;92 Suppl 3:48-9.
Psathakis D, et al. Blood selenium and glutathione peroxidase status in patients with colorectal cancer. Dis Colon Rectum 1998 Mar;41(3):328-35.
Vucelic B, et al. [Differences in serum selenium concentration in probands and patients with colorectal neoplasms in Zagreb, Croatia]. Acta Med Austriaca 1994;21(1):19-23.
Surg Oncol, 2000 Mar, 18:2, 100-5.
Combs GF Jr.Chemopreventive mechanisms of selenium. Med Klin 1999 Oct 15;94 Suppl 3:18-24.
Clark LC, et al. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol 1998 May;81(5):730-4.
Decensi A, et al. Recent advances in cancer chemoprevention, with emphasis on breast and colorectal cancer. Eur J Cancer 2000 Apr 1;36(6):694-709.
Combs GF Jr, et al. Reduction of cancer risk with an oral supplement of selenium. Biomed Environ Sci 1997 Sep;10(2-3):227-34.
Combs GF Jr, et al. Reduction of cancer mortality and incidence by selenium supplementation. Med Klin 1997 Sep 15;92 Suppl 3:42-5.
Yang CS. Vitamin nutrition and gastroesophageal cancer. J Nutr 2000 Feb;130(2S Suppl):338S-339S.
Clark LC, et al. Plasma selenium concentration predicts the prevalence of colorectal adenomatous polyps. Cancer Epidemiol Biomarkers Prev 1993 Jan-Feb;2(1):41-6.
Clark LC, et al. Selenium in forage crops and cancer mortality in U.S. counties. Arch Environ Health 1991 Jan-Feb;46(1):37-42.
Schrauzer GN. Selenium and cancer: a review. Bioinorg Chem 1976;5(3):275-81.
Yu MW, et al. Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection. Am J Epidemiol 1999 Aug 15;150(4):367-74.
Berkson BM. A conservative triple antioxidant approach to the treatment of hepatitis C. Combination of alpha lipoic acid (thioctic acid), silymarin, and selenium: three case histories. Med Klin 1999 Oct 15;94 Suppl 3:84-9.
Look MP, et al. Interferon/antioxidant combination therapy for chronic hepatitis C--a controlled pilot trial. Antiviral Res 1999 Sep;43(2):113-22.
Baum MK, et al. High risk of HIV-related mortality is associated with selenium deficiency. J Acquir Immune Defic Syndr Hum Retrovirol 1997 Aug 15;15(5):370-4.
Chandra RK. Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet 1992 Nov 7;340(8828):1124-7.
Girodon F, et al. Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial. Ann Nutr Metab 1997;41(2):98-107.
Nenci GG, et al. [Diabetes, coagulation and vascular events]. Recenti Prog Med 2000 Feb;91(2):86-90.
Sharma A, et al. Evaluation of oxidative stress before and after control of glycemia and after vitamin E supplementation in diabetic patients. Metabolism 2000 Feb;49(2):160-2.
Ferber P, et al. High dose supplementation of RRR-alpha-tocopherol decreases cellular hemostasis but accelerates plasmatic coagulation in type 2 diabetes mellitus. Horm Metab Res 1999 Dec;31(12):665-71.
Paolisso G, et al. Chronic vitamin E administration improves brachial reactivity and increases intracellular magnesium concentration in type II diabetic patients. J Clin Endocrinol Metab 2000 Jan;85(1):109-15.
Kaneto H, et al. Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes 1999 Dec;48(12):2398-406.
Anderson JW, et al. Antioxidant supplementation effects on low-density lipoprotein oxidation for individuals with type 2 diabetes mellitus. J Am Coll Nutr 1999 Oct;18(5):451-61.
Ferreira FM, et al. Decreased susceptibility to lipid peroxidation of Goto-Kakizaki rats: relationship to mitochondrial antioxidant capacity. Life Sci 1999;65(10):1013-25.
Skrha J, et al. Insulin action and fibrinolysis influenced by vitamin E in obese Type 2 diabetes mellitus. Diabetes Res Clin Pract 1999 Apr;44(1):27-33.
Gazis A, et al. Effect of oral vitamin E (alpha-tocopherol) supplementation on vascular endothelial function in Type 2 diabetes mellitus. Diabet Med 1999 Apr;16(4):304-11.
Davi G, et al. In vivo formation of 8-iso-prostaglandin f2alpha and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation. Circulation 1999 Jan 19;99(2):224-9.
Tutuncu NB, et al. Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes: a preliminary study. Diabetes Care 1998 Nov;21(11):1915-8.
Chung TW, et al. Reducing lipid peroxidation stress of erythrocyte membrane by alpha-tocopherol nicotinate plays an important role in improving blood rheological properties in type 2 diabetic patients with retinopathy. Diabet Med 1998 May;15(5):380-5
Yoshida H, et al. Vitamin E/lipid peroxide ratio and susceptibility of LDL to oxidative modification in non-insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol 1997 Jul;17(7):1438-46.
Reaven P. Dietary and pharmacologic regimens to reduce lipid peroxidation in non-insulin-dependent diabetes mellitus. Am J Clin Nutr 1995 Dec;62(6 Suppl):1483S-1489S.
Salonen JT, et al. Increased risk of non-insulin dependent diabetes mellitus at low plasma vitamin E concentrations: a four year follow up study in men. BMJ 1995 Oct 28;311(7013):1124-7.
Caballero B. Vitamin E improves the action of insulin. Nutr Rev 1993 Nov;51(11):339-40.
Balabolkin MI, et al. [Effect of high doses of tocopherol on the processes of lipid peroxidation and insulin secretion in patients with non-insulin-dependent diabetes mellitus]. [Article in Russian] Probl Endokrinol (Mosk) 1994 May-Jun;40(3):10-2.
Meydani SN, Vitamin E and Immunity. JAMA (1997 May 7) 277(17):1380-6.
Meydani M, et al. The effect of long-term dietary supplementation with antioxidants. Ann N Y Acad Sci 1998 Nov 20;854:352-60.
Gey KF Vitamins E plus C and interacting conutrients required for optimal health. A critical and constructive review of epidemiology and supplementation data regarding cardiovascular disease and cancer. Biofactors 1998;7(1-2):113-74.
Sokoloski JA, et al. Induction of the differentiation of HL-60 promyelocytic leukemia cells by vitamin E and other antioxidants in combination with low levels of vitamin D3: possible relationship to NF-kappaB. Leukemia 1997 Sep;11(9):1546-53
Swain RA, et al. Therapeutic uses of vitamin E in prevention of atherosclerosis. Altern Med Rev 1999 Dec;4(6):414-23.
Wu D, et al. Effect of vitamin E on human aortic endothelial cell production of chemokines and adhesion to monocytes. Atherosclerosis 1999 Dec;147(2):297-307.
Davey PJ, et al. Cost-effectiveness of vitamin E therapy in the treatment of patients with angiographically proven coronary narrowing (CHAOS trial). Cambridge Heart Antioxidant Study. Am J Cardiol 1998 Aug 15;82(4):414-7.
Polasek J. Acetylsalicylic acid and vitamin E in prevention of arterial thrombosis. Can J Cardiol 1997 May;13(5):533-5.
Hoogwerf BJ, et al. The HOPE study. Ramipril lowered cardiovascular risk, but vitamin E did not. Cleve Clin J Med 2000 Apr;67(4):287-93.
Matthai J. Vitamin E updated. Indian J Pediatr 1996 Mar-Apr;63(2):242-53.
Floreani A, et al. Plasma antioxidant levels in chronic cholestatic liver diseases. Aliment Pharmacol Ther 2000 Mar;14(3):353-8.
Watson JP, et al. Case report: oral antioxidant therapy for the treatment of primary biliary cirrhosis: a pilot study. J Gastroenterol Hepatol 1999 Oct;14(10):1034-40.
Copp RP, et al. Localization of alpha-tocopherol transfer protein in the brains of patients with ataxia with vitamin E deficiency and other oxidative stress related neurodegenerative disorders. Brain Res 1999 Mar 20;822(1-2):80-7.
Tanyel MC, et al. Neurologic findings in vitamin E deficiency. Am Fam Physician 1997 Jan;55(1):197-201.
326.Arria AM, et al. Vitamin E deficiency and psychomotor dysfunction in adults with primary biliary cirrhosis. Am J Clin Nutr 1990 Aug;52(2):383-90.
327.Winklhofer-Roob BM, et al. Short-term changes in erythrocyte alpha-tocopherol content of vitamin E-deficient patients with cystic fibrosis. Am J Clin Nutr 1992 Jan;55(1):100-3.
Margolis S, et al. Nutritional management of plasma lipid disorders. J Am Coll Nutr 1989;8 Suppl:33S-45S.
Jeffrey GP, et al. Vitamin E deficiency and its clinical significance in adults with primary biliary cirrhosis and other forms of chronic liver disease. J Hepatol 1987 Jun;4(3):307-17.
Perlmutter DH, et al. Intramuscular vitamin E repletion in children with chronic cholestasis. Am J Dis Child 1987 Feb;141(2):170-4.
Knight RE, et al. Neurologic syndrome associated with low levels of vitamin E in primary biliary cirrhosis. Gastroenterology 1986 Jul;91(1):209-11.
Larsen PD, et al. Vitamin E deficiency associated with vision loss and bulbar weakness. Ann Neurol 1985 Dec;18(6):725-7.
Machlin LJ.Clinical uses of vitamin E. Acta Vitaminol Enzymol 1985;7 Suppl:33-43.
Morrow MJ Neurologic complications of vitamin E deficiency: case report and review of the literature. Bull Clin Neurosci 1985;50:53-60.
Saito K, et al. Pathology of chronic vitamin E deficiency in fatal familial intrahepatic cholestasis (Byler disease). Virchows Arch A Pathol Anat Histol 1982 Aug;396(3):319-30.
Rosenblum JL, et al. A progressive neurologic syndrome in children with chronic liver disease. N Engl J Med 1981 Feb 26;304(9):503-8.
Franceschi S Nutrients and food groups and large bowel cancer in Europe. Eur J Cancer Prev 1999 Dec;9 Suppl 1:S49-52.
Woodson K, et al. Serum alpha-tocopherol and subsequent risk of lung cancer among male smokers. J Natl Cancer Inst 1999 Oct 20;91(20):1738-43.
Lopez-Carrillo L, et al. Nutrient intake and gastric cancer in Mexico. Int J Cancer 1999 Nov 26;83(5):601-5.
Ronco A, et al. Dietary antioxidants and lung cancer risk: a case-control study in Uruguay. Nutr Cancer 1999;34(1):100-10.
Yang CS Vitamin nutrition and gastroesophageal cancer. J Nutr 2000 Feb;130(2S Suppl):338S-339S.
Ahmed MI, et al. Lipid peroxidation and antioxidant status in human cervical carcinoma. Dis Markers 1999 Dec;15(4):283-91.
Elattar TM, et al. Biphasic action of vitamin E on the growth of human oral squamous carcinoma cells. Anticancer Res 1999 Jan-Feb;19(1A):365-8.
Launoy G, et al. Diet and squamous-cell cancer of the oesophagus: a French multicentre case-control study. Int J Cancer 1998 Mar 30;76(1):7-12.
Bairati I, et al. [Prevention of second primary cancer with vitamin supplementation in patients treated for head and neck cancers]. Bull Cancer Radiother 1996;83(1):12-6.
El Attar TM, et al. Vitamin E succinate potentiates the inhibitory effect of prostaglandins on oral squamous carcinoma cell proliferation. Prostaglandins Leukot Essent Fatty Acids 1995 Jan;52(1):69-73.
Gottlober P, et al. [The treatment of cutaneous radiation-induced fibrosis with pentoxifylline and vitamin E. An empirical report]. Strahlenther Onkol 1996 Jan;172(1):34-8.
348.Schwartz JL, et al. Altered cytokeratin expression in carcinogenesis inhibition by antioxidant nutrients. Nutr Cancer 1995;24(1):47-56.
ElAttar TM, et al. Inhibition of human oral squamous carcinoma cell (SCC-25) proliferation by prostaglandin E2 and vitamin E succinate. J Oral Pathol Med 1993 Oct;22(9):425-7.
Schwartz JL, et al. Molecular and biochemical reprogramming of oncogenesis through the activity of prooxidants and antioxidants. Ann N Y Acad Sci 1993 May 28;686:262-78; discussion 278-9.
Schwartz J, et al. The selective cytotoxic effect of carotenoids and alpha-tocopherol on human cancer cell lines in vitro. J Oral Maxillofac Surg 1992 Apr;50(4):367-73; discussion 373-4.
ElAttar TM, et al. Inhibition of growth in oral squamous carcinoma cells by cyclopentenone prostaglandins: comparison with chemotherapeutic agents. Prostaglandins Leukot Essent Fatty Acids 1997 Jun;56(6):461-5.
Klipstein-Grobusch K, et al. Dietary antioxidants and risk of myocardial infarction in the elderly: the Rotterdam Study. Am J Clin Nutr 1999 Feb;69(2):261-6.
Gey KF Vitamins E plus C and interacting conutrients required for optimal health. A critical and constructive review of epidemiology and supplementation data regarding cardiovascular disease and cancer. Biofactors 1998;7(1-2):113-74.
Schroder H, et al. Nutrition antioxidant status and oxidative stress in professional basketball players: effects of a three compound antioxidative supplement. Int J Sports Med 2000 Feb;21(2):146-50.
Welch RW, et al. Dietary antioxidant supplementation and DNA damage in smokers and nonsmokers. Nutr Cancer 1999;34(2):167-72 .
Chen D, et al. [The inhibitory effects of antioxidant vitamins on serum oxLDL and experimental atherosclerosis of rabbits]. Chung Kuo I Hsueh Ko Hsueh Yuan Hsueh Pao 1997 Dec;19(6):451-5.
Fillion L, et al. Beta-carotene enhances the recovery of lymphocytes from oxidative DNA damage. Acta Biochim Pol 1998;45(1):183-90 .
Linselsen J., et al. Effect of a single oral dose of antioxidant mixture (vitamin E, carotenoids) on the formation of cholesterol oxidation products after ex vivo LDL oxidation in humans. Eur J Med Res 1998 Feb 21;3(1-2):5-12.
Dixon ZR, et al. The effect of a low carotenoid diet on malondialdehyde-thiobarbituric acid (MDA-TBA) concentrations in women: a placebo-controlled double-blind study. Eur J Med Res 1998 Feb 21;3(1-2):5-12.
Sumida S, et al. Effect of a single bout of exercise and beta-carotene supplementation on the urinary excretion of 8-hydroxy-deoxyguanosine in humans. Free Radic Res 1997 Dec;27(6):607-18.
Meraji S, et al. Enhanced plasma level of lipid peroxidation in Iranians could be improved by antioxidants supplementation. Eur J Clin Nutr 1997 May;51(5):318-25.
Omaye ST, et al. Blood antioxidants changes in young women following beta-carotene depletion and repletion. J Am Coll Nutr 1996 Oct;15(5):469-74.
Kanter MM, et al. Effects of an antioxidant vitamin mixture on lipid peroxidation at rest and postexercise. J Appl Physiol 1993 Feb;74(2):965-9.
Chao WH, et al. Oxidative stress in humans during work at moderate altitude. J Nutr 1999 Nov;129(11):2009-12.
Bunout D, et al. Effects of supplementation with folic acid and antioxidant vitamins on homocysteine levels and LDL oxidation in coronary patients. Nutrition 2000 Feb;16(2):107-10.
Lee BM, et al. Inhibition of oxidative DNA damage, 8-OHdG, and carbonyl contents in smokers treated with antioxidants (vitamin E, vitamin C, beta-carotene and red ginseng). Cancer Lett 1998 Oct 23;132(1-2):219-27.
Howard DJ, et al. Oxidative stress induced by environmental tobacco smoke in the workplace is mitigated by antioxidant supplementation. Cancer Epidemiol Biomarkers Prev 1998 Nov;7(11):981-8.
Porrini M, et al. Lymphocyte lycopene concentration and DNA protection from oxidative damage is increased in women after a short period of tomato consumption. J Nutr 2000 Feb;130(2):189-92.
Steinberg FM, et al. Antioxidant vitamin supplementation and lipid peroxidation in smokers. Am J Clin Nutr 1998 Aug;68(2):319-27 Published erratum appears in Am J Clin Nutr 1999 Jun;69(6):1293.
Stahl W, et al. Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein. FEBS Lett 1998 May 8;427(2):305-8.
Fleshner NE, et al. Diet, androgens, oxidative stress and prostate cancer susceptibility. Cancer Metastasis Rev 1998-99;17(4):325-30.
Rao AV, et al. Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: a case-control study. Nutr Cancer 1999;33(2):159-64.
Riso P, et al.Does tomato consumption effectively increase the resistance of lymphocyte DNA to oxidative damage? Am J Clin Nutr 1999 Apr;69(4):712-8.
Lowe GM, et al. Lycopene and beta-carotene protect against oxidative damage in HT29 cells at low concentrations but rapidly lose this capacity at higher doses. Free Radic Res 1999 Feb;30(2):141-51.
Stahl W, et al. Carotenoids and carotenoids plus vitamin E protect against ultraviolet light-induced erythema in humans. Am J Clin Nutr 2000 Mar;71(3):795-8.
Blot WJ. Vitamin/mineral supplementation and cancer risk: international chemoprevention trials. Proc Soc Exp Biol Med 1997 Nov;216(2):291-6.
Kerstin Klipstein-Grobusch, et al. Original Research Communications Dietary antioxidants and risk of myocardial infarction in the elderly: the Rotterdam Study1,2,3 American Journal of Clinical Nutrition, Vol. 69, No. 2, 261-266, February 1999.
Anderson JW, et al. Antioxidant supplementation effects on low-density lipoprotein oxidation for individuals with type 2 diabetes mellitus. Am Coll Nutr 1999 Oct;18(5):451-61.
Gann PH, et al. Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res 1999 Mar 15;59(6):1225-30.
Murata M, et al. Oxidative DNA damage by vitamin A and its derivative via superoxide generation. J Biol Chem 2000 Jan 21;275(3):2003-8.
Knekt P, et al. Serum antioxidant vitamins and risk of cataract. BMJ 1992 Dec 5;305(6866):1392-4.
Riedl J, et al. Some dietary fibers reduce the absorption of carotenoids in women. J Nutr 1999 Dec;129(12):2170-6.
Castenmiller JJ, et al. beta-carotene does not change markers of enzymatic and nonenzymatic antioxidant activity in human blood. J Nutr 1999 Dec;129(12):2162-9.
Speizer FE, et al. Prospective study of smoking, antioxidant intake, and lung cancer in middle-aged women (USA). Cancer Causes Control 1999 Oct;10(5):475-82.
Ascherio A, et al. Relation of consumption of vitamin E, vitamin C, and carotenoids to risk for stroke among men in the United States. Ann Intern Med 1999 Jun 15;130(12):963-70.
Shaish A, et al. Dietary beta-carotene and alpha-tocopherol combination does not inhibit atherogenesis in an ApoE-deficient mouse model. Arterioscler Thromb Vasc Biol 1999 Jun;19(6):1470-5.
Lugli SM, et al. Stimulation of cell division in the rat by NaCl, KCl, MgCl2, and CaCl2, and inhibition of the sodium chloride effect on the glandular stomach by ascorbic acid and beta-carotene. J Cancer Res Clin Oncol 1999;125(3-4):209-13.
Girodon F, et al. Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN. VIT. AOX. geriatric network. Arch Intern Med 1999 Apr 12;159(7):748-54.
West KP Jr, et al. Double blind, cluster randomised trial of low dose supplementation with vitamin A or beta-carotene on mortality related to pregnancy in Nepal. The NNIPS-2 Study Group. BMJ 1999 Feb 27;318(7183):570-5.
Faulks RM, et al. Changes in plasma carotenoid and vitamin E profile during supplementation with oil palm fruit carotenoids. J Lab Clin Med 1998 Dec;132(6):507-11.
Romieu I, et al. Antioxidant supplementation and respiratory functions among workers exposed to high levels of ozone. Am J Respir Crit Care Med 1998 Jul;158(1):226-32.
Mark SD, et al. Do nutritional supplements lower the risk of stroke or hypertension? Epidemiology 1998 Jan;9(1):9-15.
Johnson MA, et al. Micronutrient supplementation and infection in institutionalized elders. Nutr Rev 1997 Nov;55(11 Pt 1):400-4.
Longnecker MP, et al. Intake of carrots, spinach, and supplements containing vitamin A in relation to risk of breast cancer. Cancer Epidemiol Biomarkers Prev 1997 Nov;6(11):887-92.
Patterson RE, et al. Vitamin supplements and cancer risk: the epidemiologic evidence. Cancer Causes Control 1997 Sep;8(5):786-802.
Tsubono Y, et al. A randomized controlled trial for chemoprevention of gastric cancer in high-risk Japanese population; study design, feasibility and protocol modification. Jpn J Cancer Res 1997 Apr;88(4):344-9.
Coodley GO, et al. Beta-carotene in HIV infection: an extended evaluation. AIDS 1996 Aug;10(9):967-73.
Zondervan KT, et al. Do dietary and supplementary intakes of antioxidants differ with smoking status? Int J Epidemiol 1996 Feb;25(1):70-9.
Iyama T, et al. beta-Carotene accumulation in mouse tissues and a protective role against lipid peroxidation. Int J Vitam Nutr Res 1996;66(4):301-5.
Weisburger JH Evaluation of the evidence on the role of tomato products in disease prevention. Proc Soc Exp Biol Med 1998 Jun;218(2):140-3.
Peng YM, et al. Concentrations of carotenoids, tocopherols, and retinol in paired plasma and cervical tissue of patients with cervical cancer, precancer, and noncancerous diseases. Cancer Epidemiol Biomarkers Prev 1998 Apr;7(4):347-50.
Garewal HS, et al. Emerging role of beta-carotene and antioxidant nutrients inprevention of oral cancer. Arch Otolaryngol Head Neck Surg 1995 Feb;121(2):141-4.
Buring JE, et al. beta-carotene and cancer chemoprevention. J Cell Biochem Suppl 1995;22:226-30.
Taylor PR, et al. Prevention of esophageal cancer: the nutrition intervention trials in Linxian, China. Linxian Nutrition Intervention Trials Study Group. Cancer Res 1994 Apr 1;54(7 Suppl):2029s -2031s.
Kardinaal AF, et al. Antioxidants in adipose tissue and risk of myocardial infarction: the EURAMIC Study. Lancet 1993 Dec 4;342(8884):1379-84.
Park E, et al. Effects of multivitamin/mineral supplementation, at nutritional doses, on plasma antioxidant status and DNA damage estimated by sister chromatid exchanges in lymphocytes in pregnant women. Int J Vitam Nutr Res 1999 Nov;69(6):396-402.
Wang XD, et al. Procarcinogenic and anticarcinogenic effects of beta-carotene. Nutr Rev 1999 Sep;57(9 Pt 1):263-72.
Hughes DA Effects of carotenoids on human immune function. Proc Nutr Soc 1999 Aug;58(3):713-8.
Stefani ED, et al. Dietary antioxidants and lung cancer risk: a case-control study in Uruguay. Nutr Cancer 1999;34(1):100-10.
Rust P, et al. Effects of long-term oral beta-carotene supplementation on lipid peroxidation in patients with cystic fibrosis. Int J Vitam Nutr Res 1998;68(2):83-7.
Smith-Warner SA, et al. Increasing vegetable and fruit intake: randomized intervention and monitoring in an at-risk population. Cancer Epidemiol Biomarkers Prev. 2000 Mar;9(3):307-17.
Pastori M, et al. Lycopene in association with alpha-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells. Biochem Biophys Res Commun 1998 Sep 29;250(3):582-5.
Giovannucci E . Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J Natl Cancer Inst 1999 Feb 17;91(4):317-31.
Perugini C, et al. Distribution of lipid-soluble antioxidants in lipoproteins from healthy subjects. II. Effects if in vivo supplementation with alphatocopherol. Pharmacol Res 2000 Jan;41(1):65-72.
Ronco A, et al. Vegetables, fruits, and related nutrients and risk of breast cancer: a case-control study in Uruguay. Nutr Cancer 1999;35(2):111-9.
Slattery ML, et al. Carotenoids and colon cancer. Am J Clin Nutr 2000 Feb;71(2):575-82.
Kantesky PA, et al. Dietary intake and blood levels of lycopene: association with cervical dysplasia among non-Hispanic, black women. Nutr Cancer 1998;31(1):31-40.
Goodman MT, et al. The association of plasma micronutrients with the risk of cervical dysplasia in Hawaii. Cancer Epidemiol Biomarkers Prev 1998 Jun;7(6):537-44.
Nagata C, et al. Serum carotenoids and vitamins and risk of cervical dysplasia from a case-control study in Japan. Br J Cancer 1999 Dec;81(7):1234-7.
Leal M, et al. Effect of lycopene on lipid peroxidation and glutathione-dependent enzymes induced by T-2 toxin in vivo. Toxicol Lett 1999 Sep 20;109(1-2):1-10.
Brown L, et al. A prospective study of carotenoid intake and risk of cataract extraction in US men. Am J Clin Nutr 1999 Oct;70(4):517-24.
Chasan-Taber L, et al. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. Am J Clin Nutr 1999 Oct;70(4):509-16.
Paetau I, et al. Carotenoids in human buccal mucosa cells after 4 wk of supplementation with tomato juice or lycopene supplements. Am J Clin Nutr 1999 Oct;70(4):490-4.
Sengupta A, et al. The anti-carcinogenic role of lycopene, abundantly present in tomato. Eur J Cancer Prev 1999 Aug;8(4):325-30.
Morris-Stiff GJ, et al. The antioxidant profiles of patients with recurrent acute and chronic pancreatitis. Am J Gastroenterol 1999 Aug;94(8):2135-40.
Grant WB. An ecologic study of dietary links to prostate cancer. Altern Med Rev 1999 Jun;4(3):162-9.
Bobak M, et al. An ecological study of determinants of coronary heart disease rates: a comparison of Czech, Bavarian and Israeli men. Int J Epidemiol 1999 Jun;28(3):437-44.
Muller H, et al. Plasma concentrations of carotenoids in healthy volunteers after intervention with carotenoid-rich foods. Eur J Nutr 1999 Feb;38(1):35-44.
Amir H, et al. Lycopene and 1,25-dihydroxyvitamin D3 cooperate in the inhibition of cell cycle progression and induction of differentiation in HL-60 leukemic cells. Nutr Cancer 1999;33(1):105-12.
Foy CJ, et al. Plasma chain-breaking antioxidants in Alzheimer's disease, vascular dementia and Parkinson's disease. QJM 1999 Jan;92(1):39-45.
Mayne ST, et al. Plasma lycopene concentrations in humans are determined by lycopene intake, plasma cholesterol concentrations and selected demographic factors. J Nutr 1999 Apr;129(4):849-54.
Suganuma H, et al. Protective effect of dietary tomato against endothelial dysfunction in hypercholesterolemic mice. Biosci Biotechnol Biochem 1999 Jan;63(1):78-82.
Garcia-Closas R, et al. Intake of specific carotenoids and flavonoids and the risk of lung cancer in women in Barcelona, Spain. Nutr Cancer 1998;32(3):154-8.
Porrini M, et al. Absorption of lycopene from single or daily portions of raw and processed tomato. Br J Nutr 1998 Oct;80(4):353-61.
Klebanov GI, et al. The antioxidant properties of lycopene. Membr Cell Biol 1998;12(2):287-300.
Paetau I, et al. Chronic ingestion of lycopene-rich tomato juice or lycopene supplements significantly increases plasma concentrations of lycopene and related tomato carotenoids in humans. Am J Clin Nutr 1998 Dec;68(6):1187-95.
Agarwal S, et al. Tomato lycopene and low density lipoprotein oxidation: a human dietary intervention study. Lipids 1998 Oct;33(10):981-4.
Palan PR, et al. Plasma levels of beta-carotene, lycopene, canthaxanthin, retinol, and alpha- and tau-tocopherol in cervical intraepithelial neoplasia and cancer. Clin Cancer Res 1996 Jan;2(1):181-5.
Black HS. Radical interception by carotenoids and effects on UV carcinogenesis. Nutr Cancer 1998;31(3):212-7.
Rao AV, et al. Bioavailability and in vivo antioxidant properties of lycopene from tomato products and their possible role in the prevention of cancer. Nutr Cancer 1998;31(3):199-203.
Chuang CZ, et al. Risk factors for coronary artery disease and levels of lipoprotein(a) and fat-soluble antioxidant vitamins in Asian Indians of USA. Indian Heart J 1998 May-Jun;50(3):285-91.
Weisburger JH, et al. Inhibition of PhIP mutagenicity by caffeine, lycopene, daidzein, and genistein. Mutat Res 1998 Aug 7;416(1-2):125-8.
Clinton SK. Lycopene: chemistry, biology, and implications for human health and disease. Nutr Rev 1998 Feb;56(2 Pt 1):35-51.
Burney PG, et al. Serologic precursors of cancer: serum micronutrients and the subsequent risk of pancreatic cancer. Am J Clin Nutr 1989 May;49(5):895-900.
Comstock GW, et al. Prediagnostic serum levels of carotenoids and vitamin E as related to subsequent cancer in Washington County, Maryland. Am J Clin Nutr 1991 Jan;53(1 Suppl):260S-264S.
Rumi G Jr, et al. Decrease of serum carotenoids in Crohn's disease. J Physiol Paris 2000 Mar-Apr; 94(2):159-61.
Smith-Warner SA, et al. Increasing vegetable and fruit intake: randomized intervention and monitoring in an at-risk population. Cancer Epidemiol Biomarkers Prev 2000 Mar;9(3):307-17.
Floreani A, et al. Plasma antioxidant levels in chronic cholestatic liver diseases. Aliment Pharmacol Ther 2000 Mar;14(3):353-8.
Schweitzer D, et al. [Age-related maculopathy. Comparative studies of patients, their children and healthy controls]. Ophthalmologe 2000 Feb;97(2):84-90.
Polidori MC, et al. Plasma levels of lipophilic antioxidants in very old patients with type 2 diabetes. Diabetes Metab Res Rev 2000 Jan-Feb;16(1):15-9.
Kim HW, et al. Dietary lutein stimulates immune response in the canine. Vet Immunol Immunopathol 2000 May 23;74(3-4):315-327.
Haegele AD, et al. Plasma xanthophyll carotenoids correlate inversely with indices of oxidative DNA damage and lipid peroxidation. Cancer Epidemiol Biomarkers Prev 2000 Apr;9(4):421-5.
Voorrips LE, et al. A prospective cohort study on antioxidant and folate intake and male lung cancer risk. Cancer Epidemiol Biomarkers Prev 2000 Apr;9(4):357-65.
Kozuki Y, et al. Inhibitory effects of carotenoids on the invasion of rat ascites hepatoma cells in culture. Cancer Lett 2000 Apr 3;151(1):111-5.
Rapp LM, et al. Lutein and zeaxanthin concentrations in rod outer segment membranes from perifoveal and peripheral human retina. Invest Ophthalmol Vis Sci 2000 Apr;41(5):1200-9.
Sumantran VN, et al. Differential regulation of apoptosis in normal versus transformed mammary epithelium by lutein and retinoic acid. Cancer Epidemiol Biomarkers Prev 2000 Mar;9(3):257-63.
Kim HW, et al. Modulation of humoral and cell-mediated immune responses by dietary lutein in cats. Vet Immunol Immunopathol 2000 Mar 15;73(3-4):331-41.
Grievink L, et al.Serum carotenoids, alpha-tocopherol, and lung function among Dutch elderly. Am J Respir Crit Care Med 2000 Mar;161(3 Pt 1):790-5.
Le Marchand L, et al. Vegetable consumption and lung cancer risk: a population-based case-control study in Hawaii. J Natl Cancer Inst 1989 Aug 2;81(15):1158-64.
Seddon JM, et al. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA 1994 Nov 9;272(18):1413-20 Published erratum appears in JAMA 1995 Feb 22;273(8):622.
Kucuk O, et al. Increased plasma level of cholesterol-5 beta,6 beta-epoxide in endometrial cancer patients. Cancer Epidemiol Biomarkers Prev 1994 Oct-Nov;3(7):571-4.
Street DA, et al. Serum antioxidants and myocardial infarction. Are low levels of carotenoids and alpha-tocopherol risk factors for myocardial infarction? Circulation 1994 Sep;90(3):1154-61.
Pamuk ER, et al. Effect of smoking on serum nutrient concentrations in African-American women. Am J Clin Nutr 1994 Apr;59(4):891-5.
Batieha AM, et al. Serum micronutrients and the subsequent risk of cervical cancer in a population-based nested case-control study. Cancer Epidemiol Biomarkers Prev 1993 Jul-Aug; 2(4):335-9.
Le Marchand L, et al. Intake of specific carotenoids and lung cancer risk. Cancer Epidemiol Biomarkers Prev 1993 May-Jun;2(3):183-7. Published erratum appears in Cancer Epidemiol Biomarkers Prev 1994 Sep;3(6):523.
Gerster H. Intermediate cancer biomarkers and their use in beta-carotene studies in humans. Int J Vitam Nutr Res 1996;66(1):3-18.
Steinmetz KA, et al. Vegetables, fruit, and lung cancer in the Iowa Women's Health Study. Cancer Res 1993 Feb 1;53(3):536-43.
Ziegler RG, et al. Does beta-carotene explain why reduced cancer risk is associated with vegetable and fruit intake? Cancer Res 1992 Apr 1;52 (7 Suppl):2060s-2066s.
Potischman N, et al. A case-control study of nutrient status and invasive cervical cancer. II. Serologic indicators. Am J Epidemiol 1991 Dec 1;134(11):1347-55.
Ito Y, et al. Relationship between serum xanthophyll levels and the consumption of cigarettes, alcohol or foods in healthy inhabitants of Japan. Int J Epidemiol 1991 Sep;20(3):615-20.
Le Marchand L, et al. Vegetable and fruit consumption in relation to prostate cancer risk in Hawaii: a re-evaluation of the effect of dietary beta-carotene. Am J Epidemiol 1991 Feb 1;133(3):215-9.
Am J Epidemiol 1991 Feb 1;133(3):215-9 Le Marchand L, et al. Vegetable and fruit consumption in relation to prostate cancer risk in Hawaii: a reevaluation of the effect of dietary beta-carotene
Micozzi MS, et al. Published erratum appears in J Natl Cancer Inst 1990 Apr 18;82(8):715 Carotenoid analyses of selected raw and cooked foods associated with a lower risk for cancer. J Natl Cancer Inst 1990 Feb 21;82(4):282-5.
Zhang ZF, et al. Adenocarcinomas of the esophagus and gastric cardia: the role of diet. Nutr Cancer 1997;27(3):298-309.
Cowan CG, et al. Antioxidant status of oral mucosal tissue and plasma levels in smokers and non-smokers. J Oral Pathol Med 1999 Sep;28(8):360-3.
Yang Y, et al. Carotenoid analysis of several dark-green leafy vegetables associated with a lower risk of cancers. Biomed Environ Sci 1996 Dec;9(4):386-92.
Clinton SK, et al. cis-trans lycopene isomers, carotenoids, and retinol in the human prostate. Cancer Epidemiol Biomarkers Prev 1996 Oct;5(10):823-33.
Steinmetz KA, et al. Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc 1996 Oct;96(10):1027-39.
Caperle M, et al. Dietary profiles and anti-oxidants in a rural population of central Italy with a low frequency of cancer. Eur J Cancer Prev 1996 Jun;5(3):197-206.
Freudenheim JL, et al. Premenopausal breast cancer risk and intake of vegetables, fruits, and related nutrients. J Natl Cancer Inst 1996 Mar 20;88(6):340-8.
Zhang ZF, et al. Adenocarcinomas of the esophagus and gastric cardia: the role of diet. Nutr Cancer 1997;27(3):298-309.
De Stefani E, et al. Dietary fiber and risk of breast cancer: a case-control study in Uruguay. Nutr Cancer 1997;28(1):14-9.
Enger SM, et al.Dietary intake of specific carotenoids and vitamins A, C, and E, and prevalence of colorectal adenomas. Cancer Epidemiol Biomarkers Prev 1996 Mar;5(3):147-53.
Howard AN, et al. Do hydroxy-carotenoids prevent coronary heart disease? A comparison between Belfast and Toulouse. Int J Vitam Nutr Res 1996;66(2):113-8.
Rock CL, et al. Carotenoids, vitamin A, and estrogen receptor status in breast cancer. Nutr Cancer 1996;25(3):281-96.
Giovannucci E, et al. Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 1995 Dec 6;87(23):1767-76.
Snodderly DM. Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins. Am J Clin Nutr 1995 Dec;62(6 Suppl):1448S-1461S.
Le Marchand L, et al. An ecological study of diet and lung cancer in the South Pacific. Int J Cancer 1995 Sep 27;63(1):18-23.
Nishino H. Cancer prevention by natural carotenoids. J Cell Biochem Suppl 1997;27:86-91.
Dorgan JF, et al. Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri. Cancer Causes Control 1998 Jan;9(1):89-97.
Goodman MT, et al. Diet, body size, physical activity, and the risk of endometrial cancer. Cancer Res 1997 Nov 15;57(22):5077-85.
Giuliano AR, et al. Antioxidant nutrients: associations with persistent human papillomavirus infection. Cancer Epidemiol Biomarkers Prev 1997 Nov;6(11):917-23.
Comstock GW, et al. The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acid, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity. Cancer Epidemiol Biomarkers Prev 1997 Nov;6(11):907-16.
Hininger I, et al. Effect of increased fruit and vegetable intake on the susceptibility of lipoprotein to oxidation in smokers. Eur J Clin Nutr 1997 Sep;51(9):601-6.
Nebeling LC, et al. Changes in carotenoid intake in the United States: the 1987 and 1992 National Health Interview Surveys. J Am Diet Assoc 1997 Sep;97(9):991-6.
Zhang S, et al.Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects. Am J Clin Nutr 1997 Sep;66(3):626-32.
Rock CL, et al.Responsiveness of carotenoids to a high vegetable diet intervention designed to prevent breast cancer recurrence. Cancer Epidemiol Biomarkers Prev 1997 Aug;6(8):617-23.
Rock CL, et al.Responsiveness of carotenoids to a high vegetable diet intervention designed to prevent breast cancer recurrence. Cancer Epidemiol Biomarkers Prev 1997 Aug;6(8):617-23.
Landrum JT, et al. A one year study of the macular pigment: the effect of 140 days of a lutein supplement. Exp Eye Res 1997 Jul;65(1):57-62.
Iribarren C. Association of serum vitamin levels, LDL susceptibility to oxidation, and autoantibodies against MDA-LDL with carotid atherosclerosis. A case-control study. The ARIC Study Investigators. Atherosclerosis Risk in Communities. Arterioscler Thromb Vasc Biol 1997 Jun;17(6):1171-7.
Nomura AM, et al. Serum micronutrients and upper aerodigestive tract cancer. Cancer Epidemiol Biomarkers Prev 1997 Jun;6(6):407-12.
Morris-Stiff GJ, et al. The antioxidant profiles of patients with recurrent acute and chronic pancreatitis. Am J Gastroenterol 1999 Aug;94(8):2135-40.
Cohen JH, et al. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst 2000 Jan 5;92(1):61-8.
Klipstein-Grobusch K, et al. Serum carotenoids and atherosclerosis. The Rotterdam Study. Atherosclerosis 2000 Jan;148(1):49-56.
Pratt S. Dietary prevention of age-related macular degeneration. J Am Optom Assoc 1999 Jan;70(1):39-47.
McEligot AJ, et al. Plasma carotenoids are biomarkers of long-term high vegetable intake in women with breast cancer. J Nutr 1999 Dec;129(12):2258-63.
Yeum KJ, et al. Fat-soluble nutrient concentrations in different layers of human cataractous lens. Curr Eye Res 1999 Dec;19(6):502-5.
Kontush A, et al. Lipophilic antioxidants in blood plasma as markers of atherosclerosis: the role of alpha-carotene and gamma-tocopherol. Atherosclerosis 1999 May;144(1):117-22.
Yu MW, et al. Plasma carotenoids, glutathione S-transferase M1 and T1 genetic polymorphisms, and risk of hepatocellular carcinoma: independent and interactive effects. Am J Epidemiol 1999 Apr 1;149(7):621-9.
Torfs CP, et al. Association between mothers' nutrient intake and their offspring's risk of gastroschisis. Teratology 1998 Dec;58(6):241-50.
Gamboa-Pinto AJ, et al. Cervical tissue and plasma concentrations of alpha-carotene and beta-carotene in women are correlated. J Nutr 1998 Nov;128(11):1933-6.
Lee BW, et al. Association between diet and lung cancer location. Am J Respir Crit Care Med 1998 Oct;158(4):1197-203.
Kohlmeier L, et al. Lycopene and myocardial infarction risk in the EURAMIC Study. Am J Epidemiol 1997 Oct 15;146(8):618-26.
Zino S, et al. Randomised controlled trial of effect of fruit and vegetable consumption on plasma concentrations of lipids and antioxidants. BMJ 1997 Jun 21;314(7097):1787-91.
Karas M, et al. Lycopene interferes with cell cycle progression and insulin-like growth factor I signaling in mammary cancer cells. Nutr Cancer 2000;36(1):101-11.
Negri E, et al. Selected micronutrients and oral and pharyngeal cancer. Int J Cancer 2000 Apr 1;86(1):122-7.
Kelloff GJ, et al. Progress in cancer chemoprevention: development of diet-derived chemopreventive agents. J Nutr 2000 Feb;130(2S Suppl):467S-471S.
Norrish AE, et al. Prostate cancer and dietary carotenoids. Am J Epidemiol 2000 Jan 15;151(2):119-23.
Weisburger JH. Mechanisms of action of antioxidants as exemplified in vegetables, tomatoes and tea. Food Chem Toxicol 1999 Sep-Oct;37(9-10):943-8.
Sengupta A, et al. The anti-carcinogenic role of lycopene, abundantly present in tomato. Eur J Cancer Prev 1999 Aug;8(4):325-30.
Thomas JA. Diet, micronutrients, and the prostate gland. Nutr Rev 1999 Apr;57(4):95-103.
Hsueh YM, et al. Low serum carotene level and increased risk of ischemic heart disease related to long-term arsenic exposure. Atherosclerosis 1998 Dec;141(2):249-57.
Schmidt R, et al.Plasma antioxidants and cognitive performance in middle-aged and older adults: results of the Austrian Stroke Prevention Study. J Am Geriatr Soc 1998 Nov;46(11):1407-10.
Weisburger JH . Evaluation of the evidence on the role of tomato products in disease prevention. Proc Soc Exp Biol Med 1998 Jun;218(2):140-3.
Kristenson M, et al. Antioxidant state and mortality from coronary heart disease in Lithuanian and Swedish men: concomitant cross sectional study of men aged 50. BMJ 1997 Mar 1;314(7081):629-33.
Kim SY, et al. Serum levels of antioxidant vitamins in relation to coronary artery disease: a case control study of Koreans. Biomed Environ Sci 1996 Sep;9(2-3):229-35.
Tavani A, et al. Risk factors for breast cancer in women under 40 years. Eur J Cancer 1999 Sep;35(9):1361-7.
Rasmussen KM, et al. Breast cancer and dietary and plasma concentrations of carotenoids and vitamin A. Am J Clin Nutr 1990 Nov;52(5):909-15.
Mezzetti M, et al. Population attributable risk for breast cancer: diet, nutrition, and physical exercise. J Natl Cancer Inst 1998 Mar 4;90(5):389-94.
La Vecchia C, et al. [Esophageal carcinoma]. Ann Ist Super Sanita 1996;32(4):551-6.
Cahill RJ, et al. Effects of vitamin antioxidant supplementation on cell kinetics of patients with adenomatous polyps. Gut 1993 Jul;34(7):963-7.
Graham S. Epidemiology of retinoids and cancer. J Natl Cancer Inst 1984 Dec;73(6):1423-8.
Wald NJ, et al. Serum beta-carotene and subsequent risk of cancer: results from the BUPA Study. Br J Cancer 1988 Apr;57(4):428-33.
Harris RW, et al. Cancer of the cervix uteri and vitamin A. Br J Cancer 1986 May;53(5):653-9.
Tavani A, et al. Beta-carotene and risk of coronary heart disease. A review of observational and intervention studies. Biomed Pharmacother 1999 Oct;53(9):409-16.
Mannisto S, et al. Diet and the risk of breast cancer in a case-control study: does the threat of disease have an influence on recall bias? J Clin Epidemiol 1999 May;52(5):429-39.
Gupta PC, et al. Influence of dietary factors on oral precancerous lesions in a population-based case-control study in Kerala, India. Cancer 1999 May 1;85(9):1885-93.
Fioretti F, et al.Risk factors for breast cancer in nulliparous women. Br J Cancer 1999 Apr;79(11-12):1923-8.
Kritchevsky SB. beta-Carotene, carotenoids and the prevention of coronary heart disease. J Nutr 1999 Jan;129(1):5-8.
Bobak M, et al. Could antioxidants play a role in high rates of coronary heart disease in the Czech Republic? Eur J Clin Nutr 1998 Sep;52(9):632-6.
Freng A, et al. Malignant epithelial tumours in the upper digestive tract: a dietary and socio-medical case-control and survival study. Eur J Clin Nutr 1998 Apr;52(4):271-8.
Brennan P, et al. A multicenter case-control study of diet and lung cancer among non-smokers. Cancer Causes Control 2000 Jan;11(1):49-58.
Schwartz JL. In vitro growth changes of oral human keratinocytes after treatment with carotenoids, retinoid, and/or DMBA. Nutr Cancer 1999;33(1):58-68.
Tan AJ, et al. [A matched case-control study on the relations between beta-carotene and lung cancer]. Chung Hua Liu Hsing Ping Hsueh Tsa Chih 1995 Aug;16(4):199-202.
Teicher BA, et al. In vivo modulation of several anticancer agents by beta-carotene. Cancer Chemother Pharmacol 1994;34(3):235-41.
Kune GA, et al. Oral and pharyngeal cancer, diet, smoking, alcohol, and serum vitamin A and beta-carotene levels: a case-control study in men. Nutr Cancer 1993;20(1):61-70.
Huang C, et al. A case-control study of dietary factors in patients with lung cancer. Biomed Environ Sci 1992 Sep;5(3):257-65.
Kune GA, et al. Diet, alcohol, smoking, serum beta-carotene, and vitamin A in male nonmelanocytic skin cancer patients and controls. Nutr Cancer 1992;18(3):237-44.
Toma S, et al. In vitro effects of beta-carotene on human oral keratinocytes from precancerous lesions and squamous carcinoma. Anticancer Drugs 1991 Dec;2(6):581-9.
Herrero R, et al. A case-control study of nutrient status and invasive cervical cancer. I. Dietary indicators. Am J Epidemiol 1991 Dec 1;134(11):1335-46.
ElAttar TM, Lin HS. Effect of retinoids and carotenoids on prostaglandin formation by oral squamous carcinoma cells. Prostaglandins Leukot Essent Fatty Acids 1991 Jul;43(3):175-8.
Schwartz JL, et al. Directed lysis of experimental cancer by beta-carotene in liposomes. Nutr Cancer 1991;16(2):107-24.
Harris RW, et al. A case-control study of dietary carotene in men with lung cancer and in men with other epithelial cancers. Nutr Cancer 1991;15(1):63-8.
Stahl W, et al. Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein. FEBS Lett 1998 May 8;427(2):305-8.