Metabolic Syndrome and Nutrients

Metabolic Syndrome is not a disease; it is a cluster of symptoms that are considered risk factors for diabetes and heart disease. These include blood pressure, waist circumference, fasting blood sugar level, triglyceride level, and HDL cholesterol level. If someone has abnormal test results for 3 of these 5 markers, that person may be considered to have metabolic syndrome. It is well established in the medical literature that people with diabetes have higher rates of heart disease and a higher death rate than the general public. Obviously, it is not desirable for any of these metabolic markers to be outside the normal range, and individually they are recognized as risk factors for heart disease and/or diabetes.

Glucose management can be helped by adequate and inhibited by inadequate nutrient intake. Chromium is recognized as essential to managing blood sugar; as is Biotin, which is a B-Complex nutrient that is not one of the essential eight B Vitamins. For herbs, the best evidence is for them helping to maintain insulin sensitivity, control sweet cravings, and perhaps to support healthy pancreatic function: Gymnema sylvestre and Stevia rebaudiana (full spectrum steviosides; not Reb A versions of stevia isolates) appear to help us to manage healthy glucose metabolism; while Banaba leaf extract is a source of corosolic acid, which appears to aid in maintaining healthy insulin sensitivity. Of course, fiber is reported to slow the increase in blood sugar after a meal.

It is far easier to suggest blood sugar supplements and even dietary changes before a drug regimen is started. Afterward, there can be serious interactions, even for fiber. Drastic dietary changes, such as changing to a whole food diet, can be risky if a set dose of medicine is taken because less of the drug may then be needed, opening the door to a real risk of a drug overdose. Patients should always disclose to their physician what supplements they are considering taking to avoid potential interactions. A moderate strength multiple vitamin formula that provides essential levels of chromium is normally allowed by the physician in such circumstances.

Dr. Thomas A. Barringer of Carolinas Medical Center in Charlotte, North Carolina reports that his studies show that multiple vitamins benefit our diabetic population. He states that “any population at risk of having marginally inadequate nutrition, such as the elderly in general, might also benefit." Dr Barringer adds: “all obese people might benefit." He pointed out that supplements are safe and relatively inexpensive, so taking a daily multivitamin is "a reasonable option" for people who are overweight, who have any type of diabetes, who may not receive adequate nutrition or whose immune system is weak. (March 4th 2003 Annals of Internal Medicine)

Dietary supplement manufacturers have one thing that they can tell customers who have diabetes: that they should consult their physician before taking any supplements. Beyond that, vitamin companies should stick to careful descriptions as to how certain products may support blood sugar already within the healthy range by various mechanisms. Going into detail about which supplements show benefit for diabetes, or any disease, is illegal under DSHEA, the Dietary Supplement Health & Education Act.
Alpha Lipoic Acid (ALA) is a potent antioxidant that helps to maintain healthy insulin sensitivity. Insulin resistance occurs from swings in blood sugar due to poor diets high in refined carbohydrates (white flour, white sugar, high fructose corn syrup) that eventually lead to the hormone Insulin becoming ineffective at moving carbohydrates out of the bloodstream into the cells. ALA has the additional benefit of protecting cells from oxidative damage, including liver cells.

Chromium is available in several forms. While some of the current evidence is on the form called chromium picolinate, other forms may be more active in controlling cholesterol, such as chromium nicotinate (polynicotinate) that’s bonded to niacin (Vitamin B3). This mineral helps us to properly manage blood sugar and is a component of Glucose Tolerance Factor. Chromium may also help maintain lean body mass (muscle) during calorie-restricted dieting.

Citrimax® is a fruit extract that helps to limit the liver's production of fat from carbohydrate. Its active compound, HCA (-Hydroxycitric acid), is an extract from the fruit rind of Garcinia cambogia that may help to downregulate the body’s ability to convert carbohydrates into stored fats.

Corosolic acid helps maintain proper insulin sensitivity, allowing sugar to be efficiently moved from the bloodstream into cells.

Gymnema sylvestre improves uptake of glucose into cells, may block ability to taste “sweet” flavors (reducing a sweet tooth), and may be useful for maintaining healthy cholesterol and triglyceride levels.
Stevia extract is a natural herbal product that is non-caloric; in its full-spectrum form providing several steviosides it may support pancreatic function and promote proper insulin sensitivity.

Women's Health Interview, October 2010

Women’s biggest health challenges tend to be related to three general areas: hormonal health (including PMS and menopause issues), pregnancy, and maintaining health as they age (bone health and avoiding chronic degenerative conditions).

Women do seem to suffer more from certain problems related to inflammatory challenges and hormonal changes. Because of their regular, or sometimes irregular hormonal cycles, there are both advantages and disadvantages compared with men; at least until menopause tends to even the field regarding heart disease, for example. Regular menstruation lowers iron stores, reducing health problems related to oxidative and microbial challenges from free radicals that can be elevated due to the actions of uncontrolled free iron. Because of this, premenopausal women tend to have lower levels of heart disease than either post-menopausal women or adult men.

Also, because of their greater reliance on three major forms of natural estrogen as a dominant hormone complex, women seem to have greater risks of getting hormonal abnormalities and elevated cancer rates related to breast, endometrial tissues, etc. There are numerous factors involved, but oxidation of estrogens into more dangerous forms has been suggested as a major contributor to those risks. The fact that certain volatile plastics containing free BPA and specific other chemicals are known to be strong estrogen mimics makes exposure to those substances very dangerous to women, in particular.

Men do share some of those risks; for example, some estrogenic agricultural chemicals widely used on lawns, golf courses, and farms (herbicides, pesticides) are suggested to elevate the risk of prostate abnormalities. But men’s consequences tend to be more subtle and drawn out than the very real risks that women face from both these exposures and lack of protective nutrients such as a range of antioxidants and detoxification aids such as silymarin, broccoli and cruciferous vegetable consumption, and various liver supporting herbs and nutrients. The regular use of NSAID anti-inflammatory drugs – often utilized for PMS and other aches and pains – is associated with side effects that similar-acting nutrients and herbs lack: negative effects include reducing availability of some important nutrients, upregulation of pain triggers, negative effects on mood, stomach and GI problems, and degenerative cascades. Bless their hearts; many women don’t have it easy.

Women who eat enough legumes, flax seeds, and other sources of plant estrogens (phytoestrogens) tend to have more manageable menstrual cycles. Certain signs, like menstrual-related migraine headaches, indicate a deficiency of adequate natural progesterone levels that can be helped either by supplying the herb Vitex (chaste berry) if premenopausal or by applying natural progesterone cream to the skin. Certain herbal formulas and isoflavones from foods are utilized to preserve healthy and more comfortable menstrual cycles.

One thing that women should do to prepare for menopause is to maintain their bone mass by exercise and getting adequate supplies of not only calcium but also vitamins C, D, and K, magnesium, boron, and other bone support nutrients. The value of an alkalinizing whole food diet is of primary importance. The presence in the diet of legumes and flax seeds eases the transition to menopause, which is a normal part of a women’s life cycle.

The existence of biofilms informs our understanding of areas where bacteria and microbes can gown in the body. The fact that certain organisms – helpful or harmful – can create a mass that is layered like chainmail to resist removal is a powerful visual image that aids in understanding why it takes so long to effect changes in our inner ecology. Ideally, we have friendly probiotic bacteria coating our GI and urinary tracts to crowd out undesirable organisms. In fact, it was recently discovered that the purpose of the appendix was to serve as a reservoir of such probiotics to help “reboot” the system in case of problems that kill off the good bacteria; of course, with antibiotics, high sugar diets, stress, and other factors lowering the vitality of our probiotics, some people will grow the nasty stuff in their appendixes, presenting a serious health risk. The ability of Candida albicans live yeast and other organisms to overgrow at undesirable levels at the expense of more beneficial probiotic microbes means that some of our layered biomass colonies are undesirable and difficult to remove quickly. D-Mannose and cranberry (blueberries, too) tend to help prevent the spread of these colonies by preventing undesirable particles from adhering to the urinary tract walls but don’t kill off existing colonies. Still, these natural substances are helpful in curtailing their spread while other strategies are implemented, such as low sugar intake or even pharmaceuticals.

To support breast health it is wise to avoid BPA plastics, don’t microwave food in plastic, don’t consume agricultural chemicals on food, eat a plant-based diet providing antioxidant-rich produce, and eat plenty of broccoli, cruciferous vegetables, and non-GMO legumes, especially soy.

Various experts warn us against eating soy, with the suggestion that plant estrogens are dangerous. I have investigated the scientific literature to determine the risk and found that the scientific consensus is that there is no risk for healthy women, and even no indication that soy foods are unsafe for women who have had breast cancer! That is amazing when you consider all of the negative theories being hyped on the Internet. Soy prevents oxidation and conversion of estrogen into its more dangerous forms, aids in liver metabolism of these hormones and various toxins, and has been “proven” to protect against heart disease (soy actually has an FDA-approved qualified health claim related to this benefit).

 

Are antioxidants worthless against heart disease?

Are antioxidants worthless against heart disease? By Neil E. Levin, CCN, DANLA 8/15/07 In a published report, A Randomized Factorial Trial of Vitamins C and E and Beta Carotene in the Secondary Prevention of Cardiovascular Events in Women (Results From the Women’s Antioxidant Cardiovascular Study), researchers concluded that, “There were no overall effects of ascorbic acid (vitamin C), vitamin E, or beta carotene on cardiovascular events among women at high risk for CVD.” (1) This is simply untrue. In order to reach that conclusion, the researchers had to count non-compliant subjects as taking vitamin E, even when it was obvious that they weren’t following the study protocol. Is that intellectually honest? I would have given the opposite conclusion. When subjects assigned to take vitamin E actually took their vitamin E, the results were significant and proved that the vitamin had benefits: “Censoring participants on noncompliance led to a significant 13% reduction in the primary end point…Reductions in secondary study end points were also stronger, with a 22% reduction in MI … a 27% reduction in stroke … and a 9% reduction in CVD mortality … There was a 23% reduction in the combination of MI, stroke, or CVD death…Among those with prior CVD, the active vitamin E group experienced fewer major CVD events …” [-11%] "A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior cardiovascular disease (RR, 0.89; 95% CI, 0.79 - 1.00 [P = .04]; P value for interaction = .07). There were no significant interactions between agents for the primary end point, but those randomized to both active vitamins C and E experienced fewer strokes (P value for interaction = .03)." Why did the researchers gloss over these admitted benefits (that those assigned to take vitamin E who actually did take it had "significant" benefitsand those with prior CVD who took the relatively low levels of C plus E experience fewer strokes)? This was wholly ignored in the study's conclusion, as well as the subsequent press release and extensive news coverage. I have found and published (2) criticisms of this particular failing (reaching improper conclusions not truly supported by the data) before: (3-10) REFERENCES: 1. Cook N, et al. A Randomized Factorial Trial of Vitamins C and E and Beta Carotene in the Secondary Prevention of Cardiovascular Events in Women. ARCH INTERN MED. VOL 167 (NO. 15), AUG 13/27, 2007 2. Levin N. Land of Confusion: How Poor Science and Misleading Media Coverage Create Public Confusion About How Dietary Supplements Affect Health. J App Nutr, Vol 55, No. 1, 2005 8-15 3. Edgar R. Miller, III, MD, PhD; et al. High-dose vitamin E supplementation may increase all-cause mortality, a dose response meta-analysis of randomized trials. Annals of Internal Medicine: Online: Nov. 10, 2004: Print: 4 January 2005 | Volume 142 Issue 1 4. A study conducted by USA Today found that more than half of the experts hired to advise the government on the safety and effectiveness of medicine had a direct financial interest in the drug or topic they were asked to evaluate. An analysis of financial conflicts of interest at 159 FDA advisory committee meetings from January 1, 1998, through June 30, 2000, found that at 92% of the meetings, at least one member had a financial conflict of interest, while at 55% of meetings, half or more of the FDA advisers had conflicts of interest. These conflicts included helping a pharmaceutical company develop a medicine, then serving on an FDA advisory committee that judges the drug. 5. Lonn E, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA. 2005 Mar 16;293(11):1338–47. PMID: 15769967 6. Blumenthal M, Farnsworth NR. Echinacea angustifolia rhinovirus infections [letter]. N Engl J Med. Nov.3, 2005;353(18):1971–1972. 7. 21 C.F.R. Pt. 119, Final Rule Declaring Dietary Supplements Containing Ephedrine Alkaloids Adulterated Because They Present an Unreasonable Risk (Published February 11, 2004) (Effective April 12, 2004) available at http://www.fda.gov/ohrms/dockets/98fr/1995n-0304-nfr0001.pdf 8. Taylor JA, Weber W, Standish L, Quinn H, Goesling J, McGann M, Calabrese C. Efficacy and safety of Echinacea in treating upper respiratory tract infections in children: A randomized controlled trial. J Amer Med Assn Dec 3, 2003;290(21):2824–30. 9. Fugh-Berman A, Myers A. Citrus aurantium, an ingredient of dietary supplements marketed for weight loss: current status of clinical and basic research. Exp Biol Med (Maywood). 2004 Sep;229(8):698–704. Review. PMID: 15337824 10. Effects of Long-term Vitamin E Supplementation on Cardiovascular Events and Cancer. JAMA. Vol. 293 No. 11, Vol. 293 No. 11, March 16, 2005

Antioxidant Confusion

Antioxidant Confusion By Neil E. Levin, CCN, DANLA Board certified clinical nutritionist with diplomate in advanced nutritional laboratory assessment March 2, 2007 A meta-analysis published in the medical journal JAMA this week reported that antioxidant vitamins do not extend life and may even increase death rates slightly. 1 These conclusions make no sense, based on the scientific record. A meta-analysis relies on a statistical model of existing science, and this model has severe limitations. Even the authors admit some of the basic problems inherent in this type of analysis. More importantly, the authors could not find a dose-dependent or cause-and-effect relationship between antioxidants and deaths (from all causes) of study participants. In other words, they couldn’t show that antioxidants actually caused any deaths or that there was risk at a particular dosage. Yet this questionable speculation received widespread publicity from the sensation-hungry media during “Sweeps Month”, dutifully spreading the lie that antioxidants are now worthless and dangerous. The researchers pooled 68 previously published trials but arbitrarily excluded all published studies that had no deaths reported from any cause. Indeed, 405 otherwise eligible studies were excluded solely for this reason, which if included would likely have dramatically changed the results and conclusion. The researchers did not disclose why they decided to exclude these. This is equivalent to playing a card game after removing all but 7 cards from the deck. (That wouldn’t be a fair game, would it?) They largely ignored the original outcome measures of the studies, many of which had shown positive results for antioxidants, to look only for deaths from any cause in a tiny segment of all published research. This arbitrary decision echoes a frequently cited complaint by scientists commenting to the journal Annals of Internal Medicine when the infamous Miller meta-analysis of vitamin E was released a few years ago, which led to a dramatic slowdown of vitamin E sales. 2 It is interesting that the Miller study’s negative conclusions about vitamin E safety have since been thoroughly debunked by a more rigorous analysis published in the American Journal of Clinical Nutrition by leading antioxidant experts. 3 It is even more interesting that the flawed Miller review was cited as a reference by the JAMA authors but the second, more thorough analysis of the same data by real nutrition experts was not. The lesson learned is that a flawed meta-analysis of nutrients by statisticians and physicians may not hold up to a more competent review done by actual experts in the field of nutrient interactions, though the initial report may have scared people and changed their behavior. Critical comments and corrections typically go ignored, uncited and unreported, in contrast with the sensational initial report. 4 I question both the selection of studies reviewed and the references cited in this meta-analysis. Obviously, excluding six times as many potentially eligible studies as were actually chosen solely because of a requirement that someone in the study population had to die unfairly magnifies negative results by dramatically reducing the pool of studies with potentially positive results and healthier populations. This negative shift is a result of limiting the combined patient population to those studies with at least one dying patient. This population shifts to those individuals who are more likely to be deficient in a variety of antioxidant substances and who are unlikely to respond to limited amounts of one or few supplemental antioxidants. The lack of additional supporting antioxidants may even sometimes increase the oxidative stress on the body. A review of antioxidant science noted, “These negative results…should not be taken as evidence that the free radical theory of aging is flawed. In fact, they prove merely that a complex organism like a human or rodent is unlikely to respond predictably to crude manipulations such as supplementation with one or a small number of compounds.” 1, 5, 6 This mirrors the JAMA authors’ admissions that “antioxidant supplements may show interdependency and may have effects only if given in combination,” and that their findings “should not be translated to potential effects of fruits or vegetables,” which are sources of numerous and varied antioxidant substances. 1 Previous studies have shown the folly of such a protocol. Some years ago an antioxidant study in Finland was halted early because of a widely reported increase in cancer rates among male smokers taking beta-carotene. 7 Headlines associated this supplement with cancer risk. Despite objections that the study was flawed, beta-carotene use dropped. A later analysis published in July 2004 took another look at that same Finnish smokers' study data, but now taking into account total antioxidant intake, which (should have) cleared away the scientific controversy. 8 A composite antioxidant index was generated for each of the 27,000 men over 14 years. The calculated amounts of carotenoids, flavonoids, Vitamin E, selenium and Vitamin C were compared to actual lung cancer rates, with a clear result: an increased intake of a combination of antioxidants lowered lung cancer risk in male smokers. Another large study has noted that high carotenoid intake, as confirmed by measures of blood levels, was associated with lower mortality rates among the elderly over a ten year period. 9 The dietary level of antioxidants is an independent predictor of plasma beta-carotene, especially in moderate alcohol drinkers. A more recent study reports, “This may explain, at least in part, the inverse relationship observed between plasma beta-carotene and risk of chronic diseases associated to high levels of oxidative stress (i.e., diabetes and CVD), as well as the failure of beta-carotene supplements alone in reducing such risk.” 10 In other words, we shouldn’t expect one or two supplemented antioxidants to compensate for a deficiency of total antioxidants in the diet. In fact, many of the protocols for supplementation in the included studies may have actually been of too low potency to achieve noticeable health benefits by remedying latent nutrient deficiencies in fragile patient populations. In other words: many of the interventions were too little, too late. Don’t blame the vitamins. The JAMA report admits that the study populations, the variety of antioxidants used, their potencies and the protocols for taking them were extremely variable, complicating their data with many uncompensated variables. Yet the authors actually claim that, “This increases the trustworthiness of our findings.” I don’t think so! One trial included gave only a single serving of antioxidants and then monitored participants for 3 months. Others used doses of as little as 10 IU of vitamin E (a low amount that is below the Daily Value) and 20 mcg of selenium 1 (an amount far below the 70 mcg DV and not anywhere near the 200+ mcg/day associated with lower cancer rates). 11, 12 I am not alone in these criticisms. Alexander Schauss, PhD, FACN has written, “The range of doses in the different trials they selected for the meta-analysis is dramatic. For example, vitamin A ranged from 1333 IU to 200,000 IU, and vitamin E from 10 IU to 1000 IU. The duration of the studies range from 28 days to 12 years. Nevertheless they were all lumped together.” An Associated Press article quoted other experts criticizing this meta-analysis: ‘Meir Stampfer, professor of nutrition and epidemiology at the Harvard School of Public Health, said the new analysis hasn't discouraged him from taking his vitamins. Stampfer said the studies were too diverse to pool together because they looked at various combinations and doses of antioxidants tested in different groups of people. The trials ranged from a three-month study of 109 elderly nursing home residents to a 12-year study of 22,071 male doctors. "This study does not advance our understanding, and could easily lead to misinterpretation of the data," said Stampfer, who was not connected to the new report.’ The AP report also quoted Donald Berry, chairman of the department of biostatistics at the University of Texas’ M.D. Anderson Cancer Center, stating that this expert also disagreed with the researchers' finding of an increased risk of dying. "There are so many choices you can make when you're doing these analyses," he said. A study of approximately 90,000 nurses suggested that the incidence of heart disease was 30% to 40% lower among nurses with the highest intake of vitamin E from diet and supplements. Researchers found that the apparent benefit was mainly associated with intake of vitamin E from dietary supplements. High vitamin E intake from food was not associated with significant cardiac risk reduction. 13 Levels of Vitamin E above 100 IU daily are associated with decreased risk of coronary heart disease and certain types of cancer, as well as enhancement of immune function. These increased vitamin E intakes are considerably above levels obtainable from diet alone. 14, 15, 16 In a report on the Women’s Health Study published in JAMA, subjects supplementing with vitamin E were reported to have a significant 24% reduction in cardiovascular deaths. 17 Have these previously published benefits of antioxidants miraculously vanished simply because some doctors manipulated a statistical model to elicit unreliable data with no solid basis? Many of the studies included were of patients with specific, serious medical conditions, including one of elderly nursing home patients measuring incidences of bacterial infections (contrasting with a 2004 study published in JAMA noted that, “we observed a protective effect of vitamin E supplementation on upper respiratory tract infections, particularly the common cold, that merits further investigation.” 18), patients with tumors removed from their colon/rectum (antioxidants are associated with apoptosis, a desirable change that leads to death of cancer cells 19, 20), patients with age-related macular degeneration (a condition associated with a deficiency of various antioxidants 21-24), patients with coronary heart disease (a condition related to oxidative damage 14-16), dialysis patients with a history of cardiovascular disease (a condition related to oxidative damage that is reduced by supplemental vitamin E 17), cataract patients (another condition related to oxidative damage 25), male cigarette smokers/present and former cigarette smokers/asbestos workers (all related to low levels of total antioxidants and high toxic load), as well as patients with alcoholic hepatitis, cirrhosis, lupus, heart failure, ALS, etc. This meta-analysis will not stand the test of time because of its many variables, flaws and the arbitrary structuring of its statistical model. When better studies exist, often supported by blood assays, that show higher serum antioxidant levels reduce actual death rates in large populations, then no arbitrary statistical model should be able to negate that robust science with a merely theoretical danger based on such preliminary, questionable criteria. All studies cited here were published in peer-reviewed scientific journals, but that does not make them all of equal quality. Remember my story of the meta-analysis on vitamin E that was refuted by a better meta-analysis, yet both were peer-reviewed? A meta-analysis has more validity if fewer variables are included and if the selection of studies included is not biased by a presumed conclusion. Were hundreds of studies without dying participants ineligible for this particular meta-analysis review simply because of a selection bias, with an intent to demonstrate the dangers of supplementation? These scientists should know better. I see their report as an ill-disguised partisan attack by medical special interests on dietary supplements, a smokescreen for those that don’t look at the quality and quantity of well-designed studies that do show the benefits of vitamins to protect health and prevent deaths. The Lewin Group has presented evidence that the use of antioxidants could save the vision and independence of many senior citizens, while saving the public billions of dollars in healthcare costs. 26 The Institute of Medicine, part of the National Institutes of Health, after reviewing hundreds of well-designed studies, has set safe upper limits for several antioxidants at levels far above the Daily Values. 27 Antioxidants are safe, and proven so in better studies than this one. REFERENCES: 1. Bjelakovic G, et.al. Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis. JAMA 2007. 297(8):842-857 2. Miller ER 3rd, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. Epub 2004 Nov 10. Summary for patients in: Ann Intern Med. 2005 Jan 4;142(1):I40. PMID: 15537682 3. Hathcock JN, et al. Vitamins E and C are safe across a broad range of intakes. Am J Clin Nutr. 2005 Apr;81(4):736-45. Review. PMID: 15817846 4. Levin, N. Land of Confusion: How Poor Science and Misleading Media Coverage Create Public Confusion About How Dietary Supplements Affect Health. J App Nutr, Vol 55, No. 1, 2005 8-15 5. Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev. 1998 Apr;78(2):547-81. Review. PMID: 9562038 6. BLOCK, G. Are clinical trials really the answer? Am. J. Clin. Nutr. 62, Suppl.: 15175-15205, 1995 7. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994 Apr 14;330(15):1029-35. http://content.nejm.org/cgi/content/full/330/15/1029?ijkey=bd47b716724d0dad4cad0fb19337308753658337 8. Wright ME, et al. Development of a Comprehensive Dietary Antioxidant Index and Application to Lung Cancer Risk in a Cohort of Male Smokers. July 2004 American Journal of Epidemiology http://aje.oupjournals.org/cgi/content/abstract/160/1/68?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&andorexacttitle=and&andorexacttitleabs=and&fulltext=beta+carotene&andorexactfulltext=and&searchid=1100534768534_1530&stored_search=&FIRSTINDEX=0&sortspec=relevance&fdate=7/1/2004&tdate=7/31/2004&journalcode=amjepid 9. Buijsse B, et al. Plasma carotene and alpha-tocopherol in relation to 10-y all-cause and cause-specific mortality in European elderly: The Survey in Europe on Nutrition and the Elderly, a Concerted Action (SENECA). Am J Clin Nutr 2005;82:879–886. 10. Brighenti F. The total antioxidant capacity of the diet is an independent predictor of plasma beta-carotene. European Journal of Clinical Nutrition (2007) 61, 69–76. 11. Clark LC, Marshall JR. Randomized, controlled chemoprevention trials in populations at very high risk for prostate cancer: elevated prostate-specific antigen and high-grade prostatic intraepithelial neoplasia, Urology 57 (2001), pp. 185–187. 12. Duffield-Lillico, AJ, et al. Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the Nutritional Prevention of Cancer Trial, Cancer Epidemiol. Biomarkers Prev. 11 (2002), pp. 630–639. 13. Stampfer MJ, et al. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993;328:1444-9 14. Bauernfeind, J. Tocopherols in Foods. In: Vitamin E: A Comprehensive Treatise. Marcel Dekker, Inc., New York and Basel, pp. 99-167, 1980. 15. Horwitt, M.K. The Promotion of Vitamin E. J. Nutr. 116:1371-1377, 1986. 16. Weber, P., Bendich, A. and Machlin, L.J. Vitamin E and Human Health: Rationale for Determining Recommended Intake Levels. Nutrition 13:450-460, 1997. 17. I-Min Lee, MBBS, ScD; et al. Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer. The Women’s Health Study: A Randomized Controlled Trial. JAMA. 2005;294:56-65 18. Meydani SN, et al. Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. JAMA. 2004 Aug 18;292(7):828-36. Erratum in: JAMA. 2004 Sep 15;292(11):1305. PMID: 15315997 19. Narayanan BA. Chemopreventive agents alters global gene expression pattern: predicting their mode of action and targets. Curr Cancer Drug Targets. 2006 Dec;6(8):711-27. Review. PMID: 17168675 20. Valko M, et al. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44-84. Epub 2006 Aug 4. Review. PMID: 16978905 21. Chiu CJ, Taylor A. Nutritional antioxidants and age-related cataract and maculopathy. Exp Eye Res. 2007 Feb;84(2):229-45. Epub 2006 Jul 31. Review. PMID: 16879819 22. Moriarty-Craige SE, et al. Antioxidant supplements prevent oxidation of cysteine/cystine redox in patients with age-related macular degeneration. Am J Ophthalmol. 2005 Dec;140(6):1020-6. PMID: 16376645 23. Richer S, et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry. 2004 Apr;75(4):216-30. PMID: 15117055 24. Koh HH, et al. Macular Pigment Optical Density in Early, Age-Related Maculopathy (ARM); Comparisons With Normals and Effects of a Lutein Supplement. Invest Ophthalmol Vis Sci 2002; 43:2562 25. Meyer CH, Sekundo W. Nutritional supplementation to prevent cataract formation. Dev Ophthalmol. 2005;38:103-19. Review. PMID: 15604620 26. DaVanzo JE, et al. An Evidence-Based Study of the Role of Dietary Supplements in Helping Seniors Maintain their Independence. The Lewin Group Inc. January 20, 2006 27. National Institutes of Health, Institute of Medicine, Office of Dietary Supplements. Vitamin E Fact Sheet