The Facts About Omega-3 Fatty Acids and Increased Prostate Cancer Risk

A study released this week, “Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial,” published in the Journal of the National Cancer Institute (JNCI)) suggests that the omega-3 essential fatty acids EPA, DPA, and DHA - but not the omega-3 fatty acid ALA, found in flax, chia, hemp seeds, and nuts that have repeatedly been shown to lower prostate cancer rates - are somehow associated with increased risks of high-grade prostate cancer. At the same time, higher amounts of normally harmful trans fats in these subjects were associated with lower rates of advanced prostate cancer. [1] Because of the known limitations of this particular kind of study, all of these reported results were completely unproven, highly questionable, and highly unlikely to be true.

What kind of study was this? It is data mining of a previously published population study in which important variables and endpoints for fish oil's relationship to prostate cancer were not controlled, nor any cause and effect demonstrated. Because it is a secondary analysis of a largely epidemiological (population) study, it represents the lowest level of evidence in human studies because most relevant variables, confounding factors, and clinical endpoints are not systematically collected for proper analysis as they would be in an actual controlled clinical trial. Instead, the limited goal was to look for possible associations that were admittedly not rigorous enough to be considered as actual evidence of a causal relationship. As a preliminary study, it was consciously designed only to raise questions, rather than to provide answers, and it did accomplish that goal but also created a messy splash of misleading and over-emphatic headlines inaccurately suggesting that this one study somehow trumps many more robust clinical trials. So much for the media knowing of and respecting the Scientific Method. [2]

Dr Marilyn Glenville PhD, the UK’s leading nutritionist specializing in women’s health and former President of the Food and Health Forum at the Royal Society of Medicine, has noted some deficiencies in the current JNCI report; some examples: [3]

• “This is not a randomised controlled trial but a trial comparing Omega 3 levels in men with prostate cancer with healthy men. The men with prostate cancer had higher levels of Omega 3. But you cannot extrapolate cause and effect from this finding. It is like saying that if the majority of men with prostate cancer played tennis compared to healthy controls then tennis could trigger prostate cancer.”
• In 2009 the Harvard School of Public Health reported that “Omega 3 deficient diets cause up to 96,000 preventable deaths a year in the US. The researchers estimated the number of deaths resulting from 12 preventable causes and Omega 3 deficiency ranked as the sixth highest killer of Americans. A deficiency in these fats was classed as a bigger killer than high intake of trans fats.” [4]
• “…there are many cultures such as the Japanese who eat high amounts of oily fish containing Omega 3 fatty acids and yet have one of the lowest prostate cancer death rates in the world.”

Duffy MacKay, N.D., vice president, scientific and regulatory affairs of the Council for Responsible Nutrition, also noted some concerns with the report: [5]

• “Hundreds of studies over the past two decades have shown omega-3 fatty acids to have positive effects associated with cardiovascular health, perinatal health, inflammation, cognitive function, or cancer. Collectively, this body of research serves as the basis for numerous recommendations from respected organizations, scientific boards and healthcare practitioners that Americans get omega-3 fatty acids in their diets.”
• “While we encourage researchers to continue to study omega-3 fatty acids with an open mind, it is counterproductive when studying nutrition for researchers to promote their study as if it were the only piece of research that counts. In this case in particular, it is especially disingenuous for the researchers to make the kinds of assertions we've seen in the press, given their results are in stark contrast to previous epidemiologic studies that not only demonstrate no correlation between omega-3 consumption through fish and/or supplementation and the risk of prostate cancer, but in many cases also showed a protective effect against prostate cancer.”
• “One should also consider whether this study could have simply been measuring a biomarker reflecting recent intake of fish or fish oil supplements in a group of high risk cancer patients that had been told to increase their EPA and DHA levels, as compared to a group of non-cancer patients that had not been told to consume more EPA and DHA. Plasma levels of EPA and DHA reflect very recent intake and are considered a poor biomarker of long term omega-3 intake especially when compared to red blood cell levels, which reflect medium term intake. A single fish oil dose (or hearty serving of fish at lunch) results in >100 percent increase in plasma omega-3 levels. So looking at plasma levels in healthy and sick people may only provide insight into the recent habits of these individuals.”
• “The American Heart Association, the World Health Organization (WHO), the U.S. Institute of Medicine’s Food Nutrition Board (IOM FNB) and the 2010 Dietary Guidelines all have current policies advising Americans to eat more fatty fish to get the benefits of omega-3 fish oils. It is highly unlikely this one study will change that advice. Omega-3s can also be obtained by taking one of the many supplement products on the market. For those consumers who have concerns about prostate cancer or other questions about omega-3 fatty acids, we recommend speaking with your doctor or other healthcare practitioner.”

If you are a man and believe this report, then you’ll probably want to eat partially hydrogenated artificial trans fats instead of omega-3 fats for prostate health; though that change would greatly increase your risk of suffering far deadlier cardiovascular diseases, based on evidence from many clinical trials. But that would be ridiculous. In fact, many cultures around the world consume far more fish oil than Americans without having increased risks of aggressive prostate cancer; these include the Inuit people ("Eskimos"), Scandinavians, Southeast Asians, Pacific Islanders, Japanese, Filipinos, and others. 

In any case, in the absence of proper controls or any evidence of causation, we actually can’t know what these study results really mean. For example:

• Were DHA levels related to diet, supplementation, or both?
• Were fish and/or fish oils perhaps consumed as a deliberate health choice because of prior knowledge of prostate issues, rather than actually causing or aggravating those issues? In other words, could the consumption represent an attempt to improve a pre-existing condition by improving one’s nutritional status and be unrelated to the disease itself? Perhaps even suggested by medical teams as potentially helpful for patients' diet?
• If they had been collected, what would key inflammatory and oxidative markers, that are much likelier to be related to prostate health problems than long-chain omega-3 fatty acids such as DHA, have told us about these men’s state of health and disease?
• Where is the biochemical evidence that DHA itself may negatively contribute to prostate concerns? None is presented, even theoretically.

The Global Organization for EPA and DHA Omega-3s (GOED) also criticized these and numerous other some aspects of the JNCI report, among them these important points: [6]

• “The difference in mean blood plasma phospholipid fatty acids blood level for omega-3s was 4.66% in the combined cancer group versus 4.48% in the control. They are basing their results on just ca. 0.2% difference in omega-3 levels.”
• “Plasma phospholipid fatty acids as measured in this study are not a good index of long term intake and are influenced dramatically by a single meal, or even timing of a fish oil dose. A single fish oil dose massively increases LC omega 3 (typically increasing levels by 100% or more) in about 4-12 hours and then washes out around 48 hours.”
• “The study was not designed to look at omega-3 and confounded with selenium and Vitamin E used in the treatment arms.”
• “The test cohort included sick and healthy people. It is possible that sick people were taking fish oil supplements at a higher rate than the healthy individuals.”
• “A recent meta-analysis of fish consumption and prostate cancer by Szymanski et al. (2010) reported a large reduction in late stage or fatal prostate cancer among cohort studies." [7]
• "Several population based studies have shown a benefit of increased omega-3 fatty acid intakes to reducing prostate cancer risk.” [8]^, [9]

As I said earlier, this type of study raises questions about possible associations; but due to its built-in limitations, and results conflicting with most other related studies, provides no real answers.  Unfortunately, its counter-intuitive results generate sensational press coverage rarely accompanied by any true perspective on what this new study really means (not much).

In real life, most Americans and others in Western societies no longer consume the ideal amount or ratio of omega-3 fatty acids in their diet as our ancestors did a century or two ago. This reduction reportedly contributes to the large increase in chronic health problems that plague these societies. It is a public disservice to inappropriately scare people away from healthy foods and supplements, which help balance the diet in these many cases where the lack of essential nutrients is actually causing harm, based solely on such flimsy “evidence”. 

After reviewing this study I, a vegetarian, will continue to take my vegan DHA supplement twice a day with absolutely no concerns that it will negatively affect my own prostate health. Why am I not at all concerned? Because there is still no hard evidence explaining how long-chain omega-3 fatty acids like EPA and DHA may promote prostate cancer. There is still no demonstrated mode of action for this concern, and there are still no plausible explanations of any biological mechanisms that could justify the theory that long-chain omega-3 fatty acids may promote prostate cancer. My lack of concern is evidence based, after carefully reviewing the studies in question. Contrast this with the fear-mongering about fish, fish oil, and omega-3 fatty acids in foods and supplements that is overwhelmingly based on speculation, flimsy data, ignorance (on several levels), and maybe even some bias.

By Neil E. Levin, CCN, DANLA

REFERENCES:

[1] http://www.newswise.com/articles/view/605211/?sc=rssn&utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+NewswiseScinews+%28Newswise%3A+SciNews%29

[2] http://teacher.nsrl.rochester.edu/phy_labs/appendixe/appendixe.html

[3] http://www.hfma.co.uk/docs/Omega_3_and_Prostate_Risk-July2013.pdf

[4] The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors" study, April 2009, PLoS Medicine

[5] http://www.crnusa.org/CRNPR13-Omega3071113.html

[6] http://us1.campaign-archive1.com/?u=4ae075406cd789efec4e9ff09&id=6f3dc7a018&e=1704ffc192

[7] Szymanski KM, Wheeler DC, Mucci LA. Fish consumption and prostate cancer risk: a review and meta-analysis. Am J Clin Nutr. 2010;92(5):1223–1233

[8] Terry P, Lichtenstein P, Feychting M, et al. Fatty fish consumption and risk or prostate cancer. Lancet, 2001,357:1764-6.

[9] Lietzman MF, Stampfer MJ, Michaud DS, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. Am J Clin Nutr 2004;80:204-216.

Calcium & Cardiovascular Health: My review of the latest meta-analysis

At the end of July (2010) there was another nasty swipe at dietary supplements (Natural Health Products, for our Canadian friends). Again, the negative report came not from a single study, but from a particularly troubling type of report called a meta-analysis. Rising like a spider on a lethal web, this type of report keeps popping out of nowhere, attempting to make connections between studies where none may have been found before. In fact, we rarely see a competently designed meta-analysis on nutrients because there are many variables that come into play that simply don’t exist for isolated pharmaceutical drugs that aren’t (or at least aren’t supposed to be) present in our normal food supply. The interplay of nutrients affects each others’ metabolism, serum levels, and activities in a live human body. So when I see yet another meta-analysis getting major press coverage based on fairly flimsy evidence, I cringe and wonder why researchers and journalists fail to see the obvious flaws in their big story. Perhaps drug researchers are trying to branch out into nutrient research and just get in over their heads because they fail to see the complexity of nutrient research design.

The alleged danger this time: supplemental calcium was associated with a 30% increased risk of myocardial infarction, so the risks now outweigh the benefits. But was this proven? NO! Absolutely not. Nada. Zilch. Even the authors of this analysis know better than to claim that their report was definitive proof of these alleged dangers.

First of all, there was no increase in deaths in the groups given supplemental calcium. There was an increase in non-fatal heart attacks; but only in people who had already high calcium intake from their diets and also took high doses of supplemental calcium that they apparently didn’t need. And there was no problem demonstrated when calcium was given along with supplemental vitamin D, so maybe the problem was really that some folks had inadequate levels of that essential vitamin to deal with a high calcium intake.

But since vitamin D is both in the diet (as is calcium) and made from sunshine under the right conditions, these meta-analysis authors don’t really know how much vitamin D these people actually had, confounding their data. They don’t know because it would have required a rigorous study design that looked at all three intakes: food, supplements, and sunlight exposure at the times of day and year where vitamin D could be internally produced. Or at least measuring the serum before treatment to detect vitamin D levels and eliminate that as a variable. But that wasn’t done, perhaps because these researchers only looked at other people’s studies rather than running a human clinical trial themselves.

This points out perhaps the major problem with this type of study: since a meta-analysis is only a statistical model that cannibalizes previously published work to “mine” data in ways that were not planned by the original study designers, it has many built-in limitations. For example, cardiovascular outcomes were admittedly not intended as the primary endpoints in any of the 15 studies ‘Mixmastered’ together to make up this meta-analysis, so data on cardiovascular events were not gathered in the usual standardized manner. In plain English: the few cherry-picked studies included in this report had not done the type of standardization and control of variables needed to properly design a robust cardiovascular study because the original studies actually were looking at calcium’s effects on bone health, not heart health. This was, in fact, an admitted limitation of the current meta-analysis.

A good meta-analysis tries to pick the largest possible number of studies with similar designs to pool their results and in effect try to get a larger, hopefully more significant number of virtual test subjects. The farther from that model the meta-analysis gets, the more variables get introduced to confound the researchers. And since control of variables is the essential competence of the scientific method, we unfortunately find that an inexpertly executed meta-analysis is a misleading and erroneous scientific tool; like a ruler that has not been calibrated correctly and implies that our measurements are accurate when they may be way off the mark.

Researchers utilizing the imprecise tool of meta-analysis should not delude themselves that their work is definitive, because it almost never is. Nor should they become media darlings because they have espoused new theories - based on an unproven brew of mathematical models - that usually are already contradicted by a lot of better designed primary science. Nor should their attempts to re-examine previously published studies for results which were never intended to be measured scare us away from taking essential nutrients, which are commonly more healthful than harmful. As the current meta-analysis reported, the problem was that people who ate a lot of calcium who also took a lot of supplemental calcium without the benefits of taking vitamin D or other bone-forming cofactors had more non-fatal heart attacks. No one died. This implies that, at the most, one should not take a single nutrient in excess as if it were a magic drug, especially when they probably already get plenty in the diet. Don’t most of us know that already?

Nutrients are synergistic; therefore an imbalanced diet, including unneeded supplements that may tilt one even more into imbalance, may not properly support good health. Heck, I could have told you that before all this media fuss. But, with enough vitamin D the problem magically disappeared!. Supplementation of vitamin D apparently re-established good calcium metabolism, even at high levels of intake. The true issue then isn’t so much related to variations in calcium and vitamin D supplies, not to mention the unknown availability of other essential bone nutrients. It’s the misapplication of a drug model to a nutrient while ignoring known variables that affect the body’s proper use of that nutrient. One shouldn’t give a lot of calcium to those with adequate dietary intake, nor to those with insufficient vitamin D (and K, magnesium, et al) intake. This type of thought process is elementary to a nutritionist, of course, but apparently not to the well credentialed authors of many flawed drug model meta-analyses and their often overreaching conclusions.

You may be interested to know that a world-class researcher who has been working on calcium metabolism and osteoporosis for more than 50 years, the respected scientist who drafted the World Health Organization’s dietary calcium recommendations, strongly opposed the conclusions of the current calcium meta-analysis. Professor Chris Nordin from the Royal Adelaide Hospital in Australia was interviewed by ABC News. This news report cited Professor Nordin as saying that the meta-analysis was misleading because it improperly included studies involving a mixture of men and women, and the findings were not statistically significant. "Men are much more liable to heart attacks than women but women need calcium far more than men, so it is absurd to publish a study of the effect of calcium on the heart without separating men from women," he was quoted. Professor Nordin noted the fact that calcium supplements are predominantly recommended for and used by postmenopausal women because their bone loss is due to an increase in bone breakdown, which responds well to calcium supplementation (and vitamin D, if necessary). But he reports that calcium is seldom recommended for elderly men because their bone loss has a different cause, which is seldom caused by a need for more of that mineral. "Concluding that calcium supplements can lead to a 30 per cent increase in heart attack risk is quite premature and alarmist and can only set back the cause of osteoporosis prevention which should be our primary objective," he said.

According to ABC News, Osteoporosis Australia has also questioned the findings of the meta-analysis because many long-term studies have shown calcium supplements are safe and effective. In a statement posted on its website, Osteoporosis Australia says the weight of evidence to date indicates no increased risk of heart attacks from taking calcium supplements, which it says are an effective way of reducing fracture risk and bone loss in older men and women who have diets low in calcium.

This should point out the folly of well-meaning researchers who design studies to investigate topics that they don’t properly understand. In those cases, they simply don’t realize that there are other essential factors that can change everything and require a completely different and more comprehensive study design. That’s par for the course when meta-analyses are used to sort through previously published nutrient studies. Basic design flaws often make meta-analyses fatally flawed, despite the apparently sophisticated mathematical models and methods that researchers incorrectly try to apply to the data. Is it any wonder that we’re so confused about nutrition when researchers gain worldwide prominence for issuing highly questionable sensational reports that contradict the scientific consensus - but never have to say they’re sorry?

Calcium does not cause more heart attacks in well-designed primary human clinical studies. Healthy people should not be concerned about taking essential nutrients just because certain studies were flawed or performed on sick or at-risk populations and may have had negative results. Many of those negative reports have been challenged and may not have been verified and replicated in well designed clinical trails. The conclusions of such reports are sensational and well publicized precisely because they seem to negate our previous scientific consensus; which should make them more, not less, suspect. But the modern news cycle seems to thrive on such controversy, without caring how confused we get about what’s healthy and what’s not. But don’t worry; you have Honest Nutrition to help you sort it all out!

REFERENCES:

Bolland MJ, Avenell A, Baron JA, Grey A, Maclennan GS, Gamble GD, Reid IR. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ. 2010 Jul 29;341:c3691. doi: 10.1136/bmj.c3691. PubMed PMID: 20671013.

http://www.bmj.com/cgi/content/full/341/jul29_1/c3691?view=long&pmid=20671013

http://www.abc.net.au/news/stories/2010/08/03/2972399.htm?section=justin

How are vitamins C, D and K in supplements made?

Almost all D’s on the market are nature-identical synthesized forms. D3 and D2 are both naturally occurring in foods, but in supplements the same forms are usually from synthesized sources. So D3 synthesized from sheep lanolin is no more natural than D2 from plants or fungi. In fact, the D3 made in the skin-liver-kidneys from cholesterol and sunlight is also literally synthesized. Either plant sterols or animal sterols (cholesterol in humans, lanolin from sheep) are irradiated with UV-B light to make D2 or D3, respectively. It is a synthetic process, either internally or to produce the supplemental form; in much the same way that vitamin C can be synthesized by most mammals (not humans) from blood glucose in a process that mirrors the commercially synthesized nature-identical form. By the way, Vitamin K is also synthesized as the exact same form found in green foods (K1). Fermented foods like cheese can also contain K2 (MK-4), which is synthesized by microbes like bacteria.

Unbalanced Fox news report misleads about vitamin-mineral safety

Unbalanced Fox news report misleads about vitamin-mineral safety By Neil E. Levin, CCN, DANLA I watched the special health report on vitamins and minerals on FOX-32 (How Do Vitamins and Minerals Really Affect Your Body? on 2/12/08, see link below), but was disappointed that the report exaggerated the risks of vitamins and minerals and minimized their benefits without any mention of the common deficiencies that exist in the American population. For example, the report cautioned about vitamin E causing blood thinning, but the Food and Nutrition Board of the Institute of Medicine has set an upper tolerable intake level (UL) for vitamin E (alpha-tocopherol) at 1,500 IU per day, which “is the highest dose unlikely to result in bleeding problems;” though the Institute has also said that the danger of the vitamin inhibiting clotting was not convincing. In other words, taking about four times the most common strength of even a hi-potency vitamin E capsule might be a problem in terms of affecting clotting, but this potency is higher than is available as a dietary supplement and one that people are unlikely to try without specific medical advice. Yet, somehow, the far more common danger of a vitamin E deficiency was completely ignored. This, despite the fact that, according to dietary data from the National Health and Nutrition Examination Surveys, ninety percent or more of the adults studied had usual intakes below the current Estimated Average Requirement. Why is a theoretical overdose problem even mentioned in the report, especially with no balancing mention of known deficiencies and benefits? What happened to fair and balanced reporting? And what are the benefits of vitamin E supplementation? An NIH-supported USDA -Tufts University study published in the medical journal JAMA reported, “…we observed a protective effect of vitamin E supplementation on upper respiratory tract infections, particularly the common cold,” for nursing home patients taking 200 IU of vitamin E daily. And Annals of the New York Academy of Sciences reported that, “The results of this clinical trial show that vitamin E supplementation significantly reduces the incidence rate of common colds and the number of subjects who acquire a cold among elderly nursing home residents.” Zinc was also mentioned in the FOX report as a possible overdose candidate, but levels required to reach the negative side effects mentioned are between 150-450 mg per day, again requiring a consumer to take several capsules to achieve this. The highest potency I have ever seen (in 35 years) was 75 mg, though 15-50 mg products are relatively common. Yet the median intake among American adults is just over 2/3 of the Daily Value, making deficiencies far more common than overdoses. Again, the FOX report ignored the common, greater danger in favor of sensationalizing a remote possibility of overdosing. Zinc is essential for many biochemical reactions in the body, and is most notably associated with immune function and wound healing. Yet isn’t FOX essentially warning people against taking zinc, hinting that they may be in danger but without any hint of the true risks and benefits? A dietician in the report stated that there is no proof that taking extra vitamin C shortens or prevents colds. That should come as news to the researchers at the University of Pittsburgh Medical Center. Publishing results of a Review Study in the medical journal American Family Physician in February 2007, these physicians reported that, “Thirty trials involving 9,676 cold episodes showed a statistically significant decrease in illness duration with vitamin C taken before onset of symptoms…. Likewise, 15 trials involving 7,045 cold episodes demonstrated a decrease in severity scores and in days confined to the home.” While there is some little evidence (not none) that vitamin C can prevent the incidence of colds, there is significant evidence that it can shorten the duration and severity of colds. Don’t you think that the FOX report is irresponsible by highlighting rare nutrient overdoses while ignoring common deficiencies? Also, why would one person’s opinion that vitamin C is worthless against colds trump the collective evidence of 30 clinical studies that met the strict criteria of a review study? Given these gross errors, I suggest that FOX assigns fact-checkers to review all medical and health reports. Let’s put an end to the flawed practice of naively taking the word of health professionals who appear not be up-to-date on what’s published in the medical literature. This is most important when demonstrably false blanket statements are made that inappropriately dismiss the safety and efficacy of essential nutrients that are known to be deficient in most Americans’ diets. REFERENCES: http://www.myfoxchicago.com/myfox/pages/Home/Detail;jsessionid=BF06BF0BCA71AE327C05A6BA65DEB517?contentId=5757535&version=2&locale=EN-US&layoutCode=VSTY&pageId=1.1.1&sflg=1 Vitamin E Fact Sheet NIH Office of Dietary Supplements Zinc Fact Sheet NIH Office of Dietary Supplements “Thirty trials involving 9,676 cold episodes showed a statistically significant decrease in illness duration with vitamin C taken before onset of symptoms: an 8 percent decrease (95% confidence interval [CI], 3 to 13 percent) in adults and a 13.5 percent decrease (95% CI, 5 to 21 percent) in children. Likewise, 15 trials involving 7,045 cold episodes demonstrated a decrease in severity scores and in days confined to the home. Vitamin C did not decrease the incidence of cold in the general population. However, a subgroup of six trials involving runners, skiers, and soldiers participating in subarctic exercises demonstrated a 50 percent relative reduction in the risk of developing a cold (95% CI, 32 to 62 percent).” Simasek M, Blandino DA. Treatment of the common cold. Am Fam Physician. 2007 Feb 15;75(4):515-20. Review. PMID: 17323712 [PubMed - indexed for MEDLINE]. 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 [PubMed - indexed for MEDLINE] Dial S, Eitenmiller RR. 1995. Tocopherols and tocotrienols in key foods in the U.S. diet. In: Ong ASH, Niki E, Packer L, eds. Nutrition, Lipids, Health, and Disease. Champaign, IL: AOCS Press. Pp. 327–342. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids (2000). Institute of Medicine JASPREET K.C. AHUJA, JOSEPH D. GOLDMAN, and ALANNA J. MOSHFEGH. Current Status of Vitamin E Nutriture. Ann NY Acad Sci 2004 1031: 387-390. Erwin RB, et al. Dietary intake of selected minerals for the United States population: 1999-2000. Adv Data. 2004 Apr 27;(341):1-5. PMID: 15114720 [PubMed - indexed for MEDLINE] 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. JAMA. 2007 May 2;297(17):1882. PMID: 15315997 [PubMed - indexed for MEDLINE] Meydani SN, Han SN, Hamer DH. Vitamin E and respiratory infection in the elderly. Ann N Y Acad Sci. 2004 Dec;1031:214-22. Review. PMID: 15753147 [PubMed - indexed for MEDLINE]