Wall Street Journal doing a story on nutritional supplements in DS

When this story is published, I will post it up on here.

From:
"NDSC"
To:
"Recipient: Newsline"
Subject:
From the NDSC
Date:
Fri, 23 Mar 2007 10:12:07 -0400
Dear Parents,
We have been contacted by a reporter with the Wall Street Journal who is writing a story regarding nutritional/dietary supplements, and claims made that these supplements can improve cognition in individuals with Down syndrome. This reporter also plans to address claims that these supplements have curative power in other medical conditions such as Cystic Fibrosis, ALS, and Muscular Dystrophy.
If you have any experience in this area and would be willing to be interviewed for this story in the WSJ, please contact sue@ndsccenter.org.
Thank you!

Study on children who took fish oil and they experieced increased brain development

I found the study below on LEF's website. I found it rather interesting. It is known that fish oil, particularly DHA, helps the brain. But, when someone was asking some questions about the supplement they used in this study, I was intrigued by what I found. I don't see that great of a significance in this study anymore.

The supplement used in this study was called VegEPA. It is a fairly new supplement which contains EPA and Evening Primrose Oil (EPO). EPO increases inflammation, so this supplement is particularly not good for those with DS. EPA is an essential fatty acid and it is very needed, DHA is also needed. VegEPA is not a "supplement of choice", if you are looking for a good omega-3 fatty acid supplement. Here's is some more information:

LEF has some good information on DHA and the brain:
www.lef.org/magazine/mag2006/jul2006_report_dha_01.htm
www.lef.org/magazine/mag2006/may2006_cover_brain_01.html

--------

In looking at VegEPA's website. They say the following:

-----
"VegEPA is a patented omega-3 and omega-6 fatty acid supplement specifically formulated to combine the vast health benefits of ultra-pure EPA from marine fish oil (the omega-3 eicosapentaenoic acid) with cold-pressed non-raffinated organic virgin evening primrose oil (containing the omega-6 gamma linolenic acid or GLA). Intended as Igennus' clinical-grade supplement, VegEPA is now being successfully used by medical professionals in the treatment of various conditions. Unlike other supplements, VegEPA contains absolutely no DHA. To find out more about DHA, please click here"
----

On their "Why no DHA?" page (http://tinyurl.com/347g9h). they write the
following:

"A tremendous body of research justifies the use of high concentrations of EPA, and not DHA, in supplement form. While it is the case that DHA is important structurally in the brain, a consensus has emerged in the scientific and medical community that it is EPA which is the more beneficial of the omega-3 fatty acids for optimal neurological function.
More and more supplement companies are acknowledging this body of evidence and are gradually increasing the ratio of EPA to DHA to the extent that some forward-thinking companies, like ourselves, remove the DHA completely through molecular distillation. This oxygen-free process extracts the EPA, which is left 'ultra-pure' and is most bio-available to the body. The primary reason why VegEPA only contains ultra-pure EPA and absolutely no DHA is due to the fact that clinical trials show that as the ratio of EPA to DHA increases in a supplement, so does its effectiveness. In addition, some leading experts believe that DHA (docosahexaenoic acid) may inhibit the beneficial actions of EPA (eicosapentaenoic acid). "
"He explains: "In general it has been found that as the ratio of EPA to DHA rises in the supplement used in clinical trials of certain conditions, such as depression and attention-deficit hyperactivity disorder (ADHD), the ability of the supplement to improve the condition also rises."
For these reasons the EPA to DHA ratio in VegEPA capsules is the highest possible - VegEPA contains no DHA at all. Each VegEPA capsule contains around 280 mg of ultra-pure EPA.
Igennus is not negating the use of DHA in all circumstances; its importance for the developing foetus, for example, cannot be over-emphasised. DHA also has properties which make it beneficial for cardiovascular and joint health.
What should be recognised, however, is that these fatty acids have very distinct roles for health, particularly the role of EPA in brain function and mood disorders - for which DHA has little or no benefit. Studies have shown that for these conditions EPA alone is far more effective than in combination with DHA,which can inhibit the beneficial actions of EPA.
With the necessary co-factors the body can convert EPA into DHA as and when it needs it, preventing the unnecessary build-up which results from taking DHA in supplement form, thus avoiding any concerns about its high rate of oxidation. "
--------

I find this rather interesting and hard to believe. DHA is
*the* fatty acid which is in the brain. All fish oils are good for cognition and neurological processes, but DHA is basically the one that is "just for the brain." I emailed VegEPA, Dr. Leichtman and Life Extension. I have yet to hear from VegEPA and I would not be surprised if they do not respond.
Both Dr. Leichtman and LEF said that they (VegEPA) are not correct and are just trying to sell their product. I most definently agree with that. I've read so many things on the benefits of DHA, particularly for neurological function. I have no idea what this "tremendous body of research" is that they refer to that supposedly justifies no DHA.

Plus, their product is pro NOT anti-inflammatory (it has EPO in it, which promotes inflammation).

----

The study:

These Children Were Fed a Simple Diet Supplement. Within Three Months, Their Mental Powers Had Advanced by Three Years

The Scotsman 03-13-07
THE brains of children given dietary supplements for just three months underwent three years' worth of development, researchers reported yesterday. Tests involving four children aged eight to 13 showed that taking two doses of fish oils each day improved their reading, concentration, memory and problem-solving skills. Hi-tech scans also showed that taking the supplements - containing omega 3 and omega 6 fatty acids and a pure form of Evening Primrose oil which provides the essential fatty acid EPA - actually led to changes in their brains. Scientists yesterday said they were amazed by the findings. The youngsters who took part in the pilot study - Zach, George, Rachael and Gareth, who were all classed as overweight - were given the supplements, called VegEPA, and encouraged to cut down on fatty snacks and fizzy drinks and be more active. After three months, the children showed an improvement in reading age of well over a year, their handwriting became neater and they paid more attention in class. They also faced a battery of tests, including a scan to look for biochemical changes in the brain, which revealed rises in a key indicator of brain development, N-Acetylaspartate (NAA). Professor Basant Puri, lead researcher from Imperial College London, said: "The results were astonishing. In three months you might expect to see a small NAA increase. But we saw as much growth as you would normally see in three years. "It was as if these were the brains of children three years older. It means you have more connections and greater density of nerve cells, in the same way that a tree grows more branches." The parents of 13-year-old Gareth said they were astounded by the changes they saw in him. Prof Puri said: "Gareth's parents told me how he had suddenly found TV boring, as he wanted to read. Three months earlier he was saying he couldn't understand people who loved books." Although the children were asked to change their diet, there was no evidence this happened to any great extent. Prof Puri said he believed the improvements seen in concentration and behaviour were solely due to the supplement. Fife-based nutritionist Carina Norris said she strongly believed that diet does affect behaviour. "This study is yet more back-up to all the evidence that is coming out that fish oils can have a beneficial effect on children's brains and behaviour. "I am all for children taking a good quality fish oil supplement, not only for brain development but also for their cardiovascular health." However she cautioned: "More research needs to be done. A lot of the studies were on a very small scale, and weren't proper clinical trials."

-- More information:
I'm looking at VegEPA's website. They say the following:-----"VegEPA is a patented omega-3 and omega-6 fatty acid supplement specifically formulated to combine the vast health benefits of ultra-pure EPA from marine fish oil (the omega-3 eicosapentaenoic acid) with cold-pressed non-raffinated organic virgin evening primrose oil (containing the omega-6 gamma linolenic acid or GLA). Intended as Igennus' clinical-grade supplement, VegEPA is now being successfully used by medical professionals in the treatment of various conditions. Unlike other supplements, VegEPA contains absolutely no DHA. To find out more about DHA, please click here"----On their "Why no DHA?" page (http://tinyurl.com/347g9h). they write thefollowing:"A tremendous body of research justifies the use of high concentrations of EPA, and not DHA, in supplement form. While it is the case that DHA is important structurally in the brain, a consensus has emerged in the scientific and medical community that it is EPA which is the more beneficial of the omega-3 fatty acids for optimal neurological function.More and more supplement companies are acknowledging this body of evidence and are gradually increasing the ratio of EPA to DHA to the extent that some forward-thinking companies, like ourselves, remove the DHA completely through molecular distillation. This oxygen-free process extracts the EPA, which is left 'ultra-pure' and is most bio-available to the body. The primary reason why VegEPA only contains ultra-pure EPA and absolutely no DHA is due to the fact that clinical trials show that as the ratio of EPA to DHA increases in a supplement, so does its effectiveness. In addition, some leading experts believe that DHA (docosahexaenoic acid) may inhibit the beneficial actions of EPA (eicosapentaenoic acid). ""He explains: "In general it has been found that as the ratio of EPA to DHA rises in the supplement used in clinical trials of certain conditions, such as depression and attention-deficit hyperactivity disorder (ADHD), the ability of the supplement to improve the condition also rises."For these reasons the EPA to DHA ratio in VegEPA capsules is the highest possible - VegEPA contains no DHA at all. Each VegEPA capsule contains around 280 mg of ultra-pure EPA. Igennus is not negating the use of DHA in all circumstances; its importance for the developing foetus, for example, cannot be over-emphasised. DHA also has properties which make it beneficial for cardiovascular and joint health.What should be recognised, however, is that these fatty acids have very distinct roles for health, particularly the role of EPA in brain function and mood disorders - for which DHA has little or no benefit. Studies have shown that for these conditions EPA alone is far more effective than in combination with DHA,which can inhibit the beneficial actions of EPA. With the necessary co-factors the body can convert EPA into DHA as and when it needs it, preventing the unnecessary build-up which results from taking DHA in supplement form, thus avoiding any concerns about its high rate of oxidation. "

Vitamin E *decreases* death risk

The study which this article is going over is rather interesting, especially considering the fact that another study came out recently claiming that Vitamin E increases death risk (which I do not believe at all).


Epidemic Deficiency of Vitamin E

By William Faloon

If people had to rely on the news media for accurate health information, they might be influenced into making some very poor decisions.
For instance, new studies about vitamin E are published every week. The findings from virtually all of these studies, however, remain buried in scientific journals—that is, unless there is an unfavorable outcome. Since vitamin E is a popular supplement, the media turns negative results into headline news stories, thus leading Americans to believe that they do not need supplemental vitamin E.
Life Extension has analyzed the negative studies about vitamin E and exposed the many flaws in them. The major problem with these studies is that older test subjects (who are in poor health to begin with) are given alpha-tocopherol by itself. It is hard to imagine that alpha-tocopherol in isolation could reverse a lifetime of free-radical tissue damage, yet these are the kinds of studies the media has used to vilify vitamin E.1-9
Largest Study on Vitamin E Overlooked
On November 10, 2006, the largest study in medical history was published using blood levels of alpha-tocopherol as the marker of vitamin E status in male smokers.10 The purpose of this study was to correlate baseline vitamin E levels with specific causes of death and overall mortality over a 19-year period. There were 29,000 subjects initially enrolled and 13,000 deaths available for analysis.
The study results showed a significant reduction in overall mortality in those with the highest blood levels of alpha-tocopherol. When looking at specific diseases, men with the highest blood levels of alpha-tocopherol showed the following reductions in causes of death over the 19-year study period:
Disease
Mortality Reduction
Prostate cancer
32%
Ischemic stroke
37%
Hemorrhagic stroke
35%
Lung cancer
21%
Respiratory illness
42%
Despite the enormous size of this study, and the fact that it was published in a major scientific journal, the media all but ignored these remarkable findings.
How Vitamin E Protected These Men Against Disease
When discussing the biological mechanisms by which alpha-tocopherol reduced mortality across this wide spectrum of diseases, the scientists who conducted this study stated:
“As a primary fat-soluble antioxidant that protects lipids from peroxidation, alpha-tocopherol is able to scavenge mutagenic free radicals and inhibit the oxidation of LDL cholesterol, and these abilities have important implications for the prevention of carcinogenesis and atherosclerosis. . . alpha-tocopherol also has several important functions that are independent of its antioxidant activity, including modulation of gene expression, enhancements of immune responses, and suppression of tumor angiogenesis.”10
In describing why the study findings were so positive, the scientists noted that unlike in certain previous studies, test subjects with the higher alpha-tocopherol levels also displayed more beneficial gamma-tocopherol in their blood. The scientists elaborated that when alpha-tocopherol (vitamin E) is taken alone, it can deplete the body of gamma-tocopherol and antagonize the effects of vitamin K.10-15
A large body of published research documents the critical importance of gamma-tocopherol, especially when high doses of alpha-tocopherol are also taken.16-31 Researchers are finally recognizing what Life Extension members learned long ago—that is, the critical importance of following a program that includes both alpha- and gamma-tocopherol, along with vitamin K.
“Gamma-tocopherol is a powerful scavenger of reactive nitrogen oxide species and an inhibitor of the cyclooygenase-2 enzyme.”10
—American Journal of Clinical Nutrition - November 10, 2006, page 1206
In their concluding remarks, the scientists who conducted this most recent study stated:
“Our findings support a more robust role for circulating alpha-tocopherol in overall, cancer, and cardiovascular mortality than was suggested by previous studies.” 10
Shocking Deficiencies of Vitamin E
The editorial that accompanied this study revealed that 93% of American men and 96% of American women do not consume the recommended dietary allowance of vitamin E. Based on these startling statistics, the editorial questioned why doctors ever advocated that vitamin E supplements should be avoided!32,33
The editorial went on state the importance of establishing the amount of vitamin E necessary to “reduce the risk of chronic diseases,” rather than the minimal amount needed to “prevent a deficiency symptom.”
By analyzing fine details of the study, the editorial clearly demonstrated that the amount of vitamin E needed to achieve the optimal results shown in this study could be achieved “only with supplements.”
As was so adroitly pointed out by the editors, the federal government says Americans need only 12 milligrams a day of vitamin E, yet even this minute amount is not found in the diets of 93% of men and 96% of women in the United States,32 ergo the need for most Americans to take supplemental vitamin E.
“It is striking that the authors report that the men in the highest quintile of baseline serum concentrations of alpha-tocopherol had significantly lower risks of total and cause-specific mortality, including cardiovascular disease and cancer, than did the men in the lowest quintile of baseline serum concentrations of alpha-tocopherol.” 32
—Editorial - American Journal of Clinical Nutrition - November 10, 2006, page 959
Don’t Be a Victim of Drug Company Propaganda
It is in the economic interests of drug companies to steer Americans away from healthier lifestyles and dietary supplements. As more Americans fall ill to degenerative disease, drug company profits increase exponentially.
Enormous amounts of pharmaceutical dollars are spent influencing Congress, the FDA, and other federal agencies. The result is the promulgation of policies that cause Americans to be deprived of effective, low-cost means of protecting themselves against age-related disease.
The fact that the diets of more than 90% of Americans supply less than the 12 milligrams a day of vitamin E the government proclaims to be adequate is a startling revelation. It documents an epidemic deficiency of vitamin E among Americans who do not take supplements. Despite these grim statistics, the medical establishment continues to question the value of supplemental vitamin E.
As a member of the Life Extension Foundation, you gain access to scientific knowledge that could protect you against a host of common diseases—information that is too often distorted by the government and ignored by the mainstream media.

For longer life, William Faloon
References
1. Coulter ID, Hardy ML, Morton SC, et al. Antioxidants vitamin C and vitamin E for the prevention and treatment of cancer. J Gen Intern Med. 2006 Jul;21(7):735-44.
2. Lonn E, Bosch J, Yusuf S, 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.
3. Miller ER, III, Pastor-Barriuso R, Dalal D, et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46.
4. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet. 2003 Jun 14;361(9374):2017-23.
5. Pruthi S, Allison TG, Hensrud DD. Vitamin E supplementation in the prevention of coronary heart disease. Mayo Clin Proc. 2001 Nov;76(11):1131-6.
6. Marchioli R, Schweiger C, Levantesi G, Tavazzi L, Valagussa F. Antioxidant vitamins and prevention of cardiovascular disease: epidemiological and clinical trial data. Lipids. 2001;36 SupplS53-S63.
7. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000 Jan 20;342(3):154-60.
8. Anon. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet. 1999 Aug 7;354(9177):447-55.
9. Anon. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med. 1994 Apr 14;330(15):1029-35.
10. Wright ME, Lawson KA, Weinstein SJ, et al. Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Clin Nutr. 2006 Nov;84(5):1200-7.
11. Booth SL, Golly I, Sacheck JM, et al. Effect of vitamin E supplementation on vitamin K status in adults with normal coagulation status. Am J Clin Nutr. 2004 Jul;80(1):143-8.
12. Huang HY, Appel LJ. Supplementation of diets with alpha-tocopherol reduces serum concentrations of gamma- and delta-tocopherol in humans. J Nutr. 2003 Oct;133(10):3137-40.
13 Schurgers LJ, Shearer MJ, Soute BA, et al. Novel effects of diets enriched with corn oil or with an olive oil/sunflower oil mixture on vitamin K metabolism and vitamin K-dependent proteins in young men. J Lipid Res. 2002 Jun;43(6):878-84.
14. Handelman GJ, Machlin LJ, Fitch K, Weiter JJ, Dratz EA. Oral alpha-tocopherol supplements decrease plasma gamma-tocopherol levels in humans. J Nutr. 1985 Jun;115(6):807-13.
15. Traber MG, Kayden HJ. Preferential incorporation of alpha-tocopherol vs gamma-tocopherol in human lipoproteins. Am J Clin Nutr. 1989 Mar;49(3):517-26.
16. Saldeen T, Li D, Mehta JL. Differential effects of alpha- and gamma-tocopherol on low-density lipoprotein oxidation, superoxide activity, platelet aggregation and arterial thrombogenesis. J Am Coll Cardiol. 1999 Oct;34(4):1208-15.
17. Ohrvall M, Sundlof G, Vessby B. Gamma, but not alpha, tocopherol levels in serum are reduced in coronary heart disease patients. J Intern Med. 1996 Feb;239(2):111-7.
18. Cooney RV, Franke AA, Harwood PJ, et al. Gamma-tocopherol detoxification of nitrogen dioxide: superiority to alpha-tocopherol. Pro Natl Acad Sci U S A. 1993 Mar 1;90(5):1771-5.
19. Kontush A, Spranger T, Reich A, Baum K, Beisiegel U. Lipophilic antioxidants in blood plasma as markers of atherosclerosis: the role of alpha-carotene and gamma-tocopherol. Atherosclerosis. 1999 May;144(1):117-22.
20. Sjoholm A, Berggren PO, Cooney RV. gamma-tocopherol partially protects insulin-secreting cells against functional inhibition by nitric oxide. Biochem Biophys Res Commun. 2000 Oct 22;277(2):334-40.
21. Weinstein SJ, Wright ME, Pietinen P, et al. Serum alpha-tocopherol and gamma-tocopherol in relation to prostate cancer risk in a prospective study. J Nat Cancer Inst. 2005 Mar 2;97(5):396-9.
22. Jiang Q, Wong J, Ames BN. Gamma-tocopherol induces apoptosis in androgen-responsive LNCaP prostate cancer cells via caspase-dependent and independent mechanisms. Ann N Y Acad Sci. 2004 Dec;1031:399-400.
23. Helzlsouer KJ, Huang HY, Alberg AJ, Hoffman S. Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. J Natl Cancer Inst. 2000 Dec 20;92(24):2018-23.
24. Campbell S, Stone W, Whaley S, Krishnan K. Development of gamma (gamma)-tocopherol as a colorectal cancer chemopreventive agent. Crit Rev Oncol Hematol. 2003 Sep;47(3):249-59.
25. Gysin R, Azzi A, Visarius T. Gamma-tocopherol inhibits human cancer cell cycle progression and cell proliferation by down-regulation of cyclins. FASEB J. 2002 Dec;16(14):1952-4.
26. Jones KH, Liu JJ, Roehm JS, et al. Gamma-tocopheryl quinone stimulates apoptosis in drug-sensitive and multidrug-resistant cancer cells. Lipids. 2002 Feb;37(2):173-84.
27. Morris MC, Evans DA, Tangney CC, et al. Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutr. 2005 Feb;81(2):508-14.
28. Williamson KS, Gabbita SP, Mou S, et al. The nitration product 5-nitro-gamma-tocopherol is increased in the Alzheimer brain. Nitric Oxide. 2002 Mar;6(2):221-7.
29. Jiang Q, Ames BN. Gamma-tocopherol, but not alpha-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats. FASEB J. 2003 May;17(8):816-22.
30. Jiang Q, Elson-Schwab I, Courtemanche C, Ames BN. Gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11494-9.
31. Cooney RV, Harwood PJ, Franke AA, et al. Products of gamma-tocopherol reaction with NO2 and their formation in rat insulinoma (RINm5F) cells. Free Radic Biol Med. 1995 Sep;19(3):259-69.
32. Traber MG. How much vitamin E?. . . Just enough! Am J Clin Nutr. 2006 Nov;84(5):959-60.
33. Maras JE, Bermudez OI, Qiao N, Bakun PJ, Boody-Alter EL, Tucker KL. Intake of alpha-tocopherol is limited among US adults. J Am Diet Assoc. 2004 Apr;104(4):567-75.

Antioxidants - the recent study, which is very biased!

There was a recent study done on antioxiants. This review claims that antioxidants beta-carotene, vitamin E, or vitamin A increase death risk.

I was able to get the full text (click here to see it) of the study from Dr. Bjelokavic (one of the main researchers of this study). This study was very biased. I plan to look at certain things further and hope to write something up about it. It's also interesting to note that Dr. Bjelokavic did another study on antioxidant supplements for the prevention of GI cancer and he found the same results as this study. I will paste the abstract for that below.

Below is a WebMD article, the abstract of the study itself, Life Extension's response to this study, and Dr. Bjelokavic's antioxidants and GI cancer study below.

Antioxidant Supplements Raise Death Risk
Feb 26, 2007
(WebMD) Use of the popular antioxidant supplements beta-carotene, vitamin E, or vitamin A slightly increases a person's risk of death, an overview of human studies shows. The study also shows no benefit — and no harm — for vitamin C supplements. Selenium supplements tended to very slightly reduce risk of death.Oxidative stress — caused by highly reactive "free radical" compounds circulating in the blood — is a factor in most diseases.Antioxidants sweep up these free radicals. It seems to be a no-brainer that taking antioxidant supplements would protect your health. But it may not be that simple.A new, detailed analysis of human studies of beta-carotene, vitamin A, and vitamin E shows that people who take these antioxidant supplements don't live any longer than those who don't take them. In fact, those who take the supplements have an increased risk of death.The finding, reported in The Journal of the American Medical Association, comes from Goran Bjelakovic, M.D., DrMedSci, of the University of Nis in Serbia; Christian Gluud, M.D., DrMedSci, of Copenhagen University Hospital in Denmark; and colleagues."Our findings have already changed the way I counsel my patients about antioxidant supplements," Bjelakovic tells WebMD in an email interview. "According to our findings, beta-carotene, vitamin A, and vitamin E cannot be recommended. I am telling them that they should stop using these supplements.""There is no reason to take anything that hasn't been proven beneficial. And these antioxidant supplements do not seem beneficial at all," Gluud tells WebMD.Not everyone agrees. Nutritionist Andrew Shao, Ph.D., is vice president for scientific and regulatory affairs at the Council for Responsible Nutrition, a supplement-industry trade group."Consumers can feel confident in relying on their antioxidant supplements as they always have," Shao tells WebMD. "They can continue to take them knowing they will provide the same benefits — and this article does not change that."Antioxidant Supplements and Death Risk Bjelakovic, Gluud, and colleagues analyzed data from 68 randomized clinical trials of antioxidant supplements that included 232,606 people. When they looked at all the trials together, they found that the supplements offered no benefit but did no harm.However, some of the trials were more exactly controlled than others. There were 21 trials that had a "high bias risk." These trials had one or more problems with randomizing study participants to the supplement or placebo groups, with blinding both the participants and the investigators to whether participants received supplements or placebos, and/or with following up on all participants until the end of the study.So the researchers looked only at the 47 "low-bias-risk" studies — which included nearly 181,000 participants and which did not include people taking selenium. They found that: Taking vitamin A supplements increased the risk of death by 16 percent Taking beta-carotene supplements increased the risk of death by 7 percent Taking vitamin E supplements increased the risk of death by 4 percent Taking vitamin C supplements did not have any effect on risk of death Shao says it just isn't fair to study antioxidants in this way."What these authors have done is combine studies that are incredibly dissimilar in all sorts of ways," he says. "These studies looked at different nutrients at different doses at different durations with different lengths of follow-up — and in different populations, ranging from folks who were incredibly healthy to people with cancer and other diseases."Moreover, Shao says, the researchers looked only at studies in which people died. That left out 405 clinical trials, which he says skews the results in favor of death risk. And he points out that the researchers original 68 studies did not show any harm from supplements."These questions cause one to step back and wonder if the findings are relevant to the healthy population that uses these supplements to maintain healtand avoid chronic disease," Shao says. "That is a point they don't make: that antioxidants are not used to treat cancer or heart disease. They are used for disease prevention."Edgar R. Miller III, M.D., Ph.D., associate professor of medicine at Johns Hopkins University, in 2004 analyzed clinical trials of vitamin E. He found that high doses of vitamin E did more harm than good. Miller has high praise for the Bjelakovic/Gluud study."This is a great study. It is the highest form of scientific evidence," Miller tells WebMD. "I don't think that [Shao's] criticism is legitimate. I argue this is the best technique to analyze all this information."Gluud and Bjelakovic strongly disagree that they "cherry picked" only studies that fit some preconceived conclusion. They point out that all of their methods are "transparent" and open to public view."Anyone is welcome to criticize our research," Gluud says. "But my question is, what is your evidence? I think the parties that want to sell or use these antioxidant supplements in the dosages used in these trials, they want [to see only] positive evidence that it works beneficially."Advice to Consumers Kathleen Zelman, MPH, R.D., L.D., is director of nutrition for WebMD. She reviewed the Bjelakovic/Gluud study for this article."This is a very comprehensive, to-be-respected analysis. This isn't just another study coming out," Zelman says. "The bottom line is that antioxidant supplements are not a magic bullet for disease prevention. We hoped maybe they were, but they are not."If you are interested in protecting your health, Zelman says, pills aren't the answer."There is no single food or nutrient that is going to be the answer. The secret really is lifestyle," she says. "And the most important things about lifestyle are being at a healthy weight, being physically active, and eating a healthy diet."Shao says he's not persuaded to stop taking antioxidant supplements."I take antioxidant supplements every day," he says. "I know more about these nutrients than most people do, including the authors of this study, who are not nutritionists. This does not change a thing for me. You can take that to the bank."Zelman has this advice: If you plan to continue taking antioxidant supplements, don't exceed the recommended daily doses."For nutritional insurance, my suggestion would be a once-daily multivitamin," she says. "But for those people who take multiple supplements, and are going to continue to do so, heed the warning and be sure to respect the safe upper dosage limits.""If you are in doubt, take the time and go to your doctor and talk with her or him," Gluud advises.

Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention (ABSTRACT)

Systematic Review and Meta-analysis Goran Bjelakovic, MD, DrMedSci; Dimitrinka Nikolova, MA; Lise Lotte Gluud, MD, DrMedSci; Rosa G. Simonetti, MD; Christian Gluud, MD, DrMedSci JAMA. 2007;297:842-857.

Context Antioxidant supplements are used for prevention of several diseases. Objective To assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention trials. Data Sources and Trial Selection We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials. Data Extraction We included 68 randomized trials with 232 606 participants (385 publications). Data Synthesis When all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.05-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality. Conclusions Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study. Author Affiliations: The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Bjelakovic, L. L. Gluud, Simonetti, and C. Gluud and Ms Nikolova); Department of Internal Medicine, Gastroenterology and Hepatology, University of Nis, Nis, Serbia (Dr Bjelakovic); and Divisione di Medicina, Ospedale V. Cervello, Palermo, Italy (Dr Simonetti).

-- Another Flawed Attack against Antioxidants
by William Faloon, Tianan Jiang, MD/PhD, & Steven V. Joyal, MDReleased March 5, 2007

In today’s media frenzied world, science is practiced by ambush. The very day a medical study is published, it can become the headline news story of the day. This denies an opportunity for those who might disagree with the study’s design and methodologies to rebut what might be junk science. In the case of a recent study questioning the value of certain antioxidant nutrients, the flaws are so significant as to cause its findings to have little or no meaning. Within five days of this blatant attempt to discredit certain antioxidants, the Life Extension Foundation prepared this rebuttal to expose the flaws of this irrational and highly biased attack that the media used to disparage popular dietary supplements. Overview Oxidative stress is a well-recognized factor directly implicated in a number of human diseases1-2, and a great deal of scientific information supports and validates the role of antioxidants to decrease oxidative damage.3-6. The latest attack against antioxidants emblazoned across headlines is from a convoluted statistical review published in the February 28, 2007 edition of JAMA (Journal of the American Medical Association). This statistical review was developed by the same group of researchers that denounced antioxidants as without significant benefit in an article published in 20047. It takes the bold step of not only discounting all of the well-established scientific support for antioxidants in preventing disease, but brazenly declares that antioxidant vitamins increase all-cause mortality (death from all causes). Suboptimal dosages, outdated formulations, and inadequate study duration One of the problems with dietary supplement research is that it frequently evaluates nutrients that were initially popularized in the 1960s and 1970s, but comprise a mere fraction of what health conscious individuals are actually using today based upon current, up-to-date research. The JAMA review that attacked the value of antioxidants included vitamins A, C, E, and selenium and evaluated these very basic nutrients in a very wide & inconsistent dosage range: Supplement Dose range Vitamin A (synthetic) 1,333-200,000*** IU Alpha Tocopherol (synthetic) 10-5,000 IU Vitamin C (synthetic) 60 – 2,000 mg Selenium (natural) 20 – 200 mcg As an example of the strange decisions made by the JAMA authors as to which studies to exclude or include in their analysis, they selected a single dose study*** of patients using 200,000 IU of vitamin A, who were subsequently followed for 3 months.8 Several critical nutrients taken by health-conscious individuals were omitted from the JAMA analysis, along with optimal forms of these nutrients such as gamma tocopherol & natural alpha tocopherol succinate in the case of vitamin E, and CoQ10. Among the critically important nutrients that were completely or mostly ignored included fish oil, lipoic acid, carnitine, standardized fruit & vegetable extracts, B-vitamins, and minerals such as magnesium, zinc, and calcium. Life Extension long ago warned members about the potential implications of taking only the alpha tocopherol form of vitamin E. Whether this was a factor in the studies in which vitamin E did not show a positive health benefit is unknown, but the role of gamma tocopherol was not discussed as a possible reason for the synthetic alpha tocopherol failing to work in the minority of hand-selected studies used in this evaluation. For serious supplement consumers interested in maximum benefit, the nutrients that were evaluated in the negative JAMA study make up a small percentage of the many complimentary nutrients they have been taking for the past 10-20 years or more. The average duration of the studies selected for the analysis was 3.3 years, and the average age of the study subjects was 62 years. The belief that the administration of these very basic antioxidant supplements, in a wide range of suboptimal doses, could somehow reverse a lifetime of oxidative damage strains scientific credibility. Exclusion of over 91% of antioxidant studies Out of a potential total of 815 studies that assessed the effects of antioxidant supplements in the JAMA statistical review, only 68 were chosen for inclusion in this statistical review – this means that fully 91% of eligible antioxidant studies were arbitrarily excluded from the JAMA statistical analysis. Furthermore, 405 of the excluded studies showed no deaths whatsoever in any of the groups. Of the studies that were included in this flawed statistical review, several were completely misinterpreted: The JAMA statistical review incorrectly included 30 deaths from a study published in 2001, yet actual review of this study shows that there was only one death in the placebo group, one death in the drug plus antioxidant group, and no deaths in the group given only antioxidants;9 The JAMA statistical review failed to account for pre-existing risk factors in 399 of 800 Parkinson’s disease patients assigned to 2000 IU of vitamin E per day in the DATATOP trial - in fact, after adjustment for pre-existing risk factors, there was no excess mortality in the group assigned to vitamin E, nor did researchers observe any evidence of increased mortality for each additional year of exposure to high-dose through 13 years of observation.10 Even more disturbing than the studies that were misinterpreted by the JAMA authors is the fact that many large studies of significant trial duration showing benefit with antioxidants were excluded from this flawed & biased statistical review: A few examples of intentionally omitted positive studies were: A study involving over 29,092 male smokers aged 50-69 years followed prospectively for 19 years showed that men with the highest serum alpha-tocopherol levels had a 28% lower risk of total and cause-specific mortality than did those with the lowest levels, and a 21%, 29%, and 30% lower risk of deaths due to cancer, cardiovascular disease, and other causes;11 A study in 3,254 people (1,260 males and 1,994 females) aged from 39 to 85 years followed from 1989 to 1995 showed that higher serum levels of carotenoids with pro-vitamin A activity significantly reduces the risk of mortality from cardiovascular disease and colorectal cancer;12 A study in aging women that showed those with the lowest levels of alpha- and beta-carotene, lutein/zeaxanthin, and total carotenoids were significantly more likely to have increasing IL-6 levels over a period of 2 years, and those aging women with the lowest selenium levels had a significantly higher 54% risk of death over a 5-year period;13 A study in patients with aggressive, small cell lung cancer showed a clinically significant 35% decreased risk of death associated with antioxidant supplement use after adjustment for tumor stage and other risk factors;14 A study in 1,168 elderly men and women followed for 10 years showed that plasma carotene concentrations were associated with a 21% lower mortality risk for every 0.39 micromol/L increase in plasma carotene, a 41% lower mortality risk for cancer, and a 17% lower risk of mortality due to cardiovascular disease;15 A study that evaluated the effect of Vitamin E, beta carotene, and vitamin C on prostate cancer risk in over 29,000 men during 8 years of follow-up showed that supplemental beta-carotene intake at a dose level of at least 2000 micrograms per day was associated with a highly significant 52% decreased prostate cancer risk in men with low dietary beta-carotene intake as well as a dramatic, 71% decreased risk of advanced prostate cancer with increasing dose and duration of supplemental vitamin E;16 A study in 1,214 persons age 75-84 studied for over 4 years showed that those people with the lowest vitamin C plasma levels (<> 66 micromol/L) had a mortality risk nearly 50% less;17 A study that examined vitamin E and vitamin C supplement use in relation to mortality risk in 11,178 persons aged 67-105 years (Established Populations for Epidemiologic Studies of the Elderly) in 1984-1993 showed that vitamin E reduced the risk of all-cause mortality by 34%, reduced the risk of coronary disease mortality by 47%, and the simultaneous use of vitamins E and C was associated with a 42% lower risk of total mortality and 53% lower risk of coronary mortality;18 A study (Chicago Western Electric Study) that followed over 1,800 middle-aged men over a 30-year period showed that during 46,102 person-years of follow-up the risk of fatal stroke was 29% lower in the group taking the highest amount of vitamin C and beta-carotene;19 Two studies with different designs conducted in Linxian, an area of north central China with some of the world's highest rates of esophageal and stomach cancer and a population with a chronically low intake of several nutrients, showed significant reductions in mortality associated with antioxidant intake: One study showed that in 3,318 persons with esophageal dysplasia, a precursor to esophageal cancer, significantly lower total and cancer mortality risk was observed in those Chinese receiving beta-carotene, vitamin E, and selenium, and a whopping 55% decrease in mortality due to cerebrovascular disease;20 A second study in 29,584 adult Chinese followed from March 1986-May 1991 showed a significantly lower total mortality among those receiving supplementation with beta carotene, vitamin E, and selenium, with a significant 23% reduction in stomach cancer in this high-risk population;21 A study in 1,078 pregnant women infected with HIV given daily multivitamin supplements including vitamins A, C, and E showed reductions in risk of death, reduction in risk of HIV progression, and reduction in viral load;22 A study involving 15,419 children over one year showed the risk of death in the group supplemented with synthetic vitamin A (8,333 IU daily) was 54% less;23 A study with lung cancer patients over age 60 showed that those patients taking supplements including antioxidant vitamins like A, C, and E had a dramatic 68% increase in survival, from only 11 months in non-users to an astounding 41 months for the vitamin users (median survival);24 A study that showed daily oral administration of high-dose vitamin A (300,000 IU daily) was effective in reducing the number of lung cancers related to tobacco consumption and improved disease-free interval in patients surgically-treated for stage I lung cancer;25 A study in 595 critically-ill ICU patients showed that supplemental vitamin C and vitamin E reduced the risk of multiple organ system failure by an amazing, statistically significant 57% along with a shorter duration of mechanical ventilation and length of ICU stay.26 Respected scientists agree with Life Extension’s evaluation of the flawed JAMA statistical review Meir Stampfer, Professor of Nutrition and Epidemiology at the Harvard School of Public Health "This study does not advance our understanding, and could easily lead to misinterpretation of the data.”27 Balz Frei, Director and Endowed Chair, Linus Pauling Institute, Professor, Department of Biochemistry and Biophysics, Oregon State University “This is a flawed analysis…the totality of the evidence indicates that antioxidants from foods or supplements have many health benefits, including reduced risk for cardiovascular disease, some types of cancer, eye disease, and neurodegenerative disease…they are a key to an enhanced immune system and resistance to infection.”28 Jeffrey Blumberg, Director of the Antioxidants Research Laboratory at Tufts University in Boston, Massachusetts “One of the major premises of doing such a meta-analysis is that the studies should be comparable…here, they looked at primary prevention, treatment, old people, young people, smokers, nonsmokers. Only when they used their own criteria of what was good and what was bad were they able to show an increase in all-cause mortality."29 Life Extension is always vigilant in providing our members with rigorous scientific review of information on health & disease prevention Statistical analysis is a tool used to interpret and assess information. The quality of the statistical result depends in large part upon the criteria used to evaluate the data. Regrettably, Life Extension fears that the greater impact of the JAMA analysis will be to tragically cut short the lives of people who may otherwise derive lifesaving benefit from antioxidant supplements, but avoid these dietary ingredients out of fear generated by this deeply-flawed, biased statistical review. References: Sies H. Introductory remarks. In: Sies H, ed. Oxidative stress. Orlando, FL.: Academic Press; 1985:1-7. Halliwell B, Gutteridge JMC. Free Radicals. In: Biology and Medicine. 3rd ed. London, England: Oxford University Press; 1999. Papas AM. Diet and antioxidant status. In: Papas AM, ed. Antioxidant Status, Diet, Nutrition, and Health. Boca Raton, Fla: CRC Press; 1998:89-94. Halliwell B. Antioxidants in human health and disease. Annu Rev Nutr. 1996;16:33-50. Halliwell B. Antioxidant defense mechanisms: from beginning to the end (of the beginning). Free Radic Res. 1999;31:261-272. Willcox JK, Ash SL, Catignani GL. Antioxidants and prevention of chronic disease. Crit Rev Food Sci Nutr. 2004;44:275-295. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet. 2004;364:1219-1228. Murphy S, West KP Jr, Greenough WB III, Cherot Katz J, Clement L. Impact of vitamin A supplementation on the incidence of infection in elderly nursing home residents: a randomized controlled trial. Age Ageing. 1992;21:435-439. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345: 1583-1592. Marras C, McDermott MP, Rochon PA, Tanner CM, Naglie G, Rudolph A, et al. Survival in Parkinson disease: thirteen-year follow-up of the DATATOP cohort. Neurology. 2005;64:87-93. Wright ME, Lawson KA, Weinstein SJ, Pietinen P, Taylor PR, Virtamo J, Albanes D. Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Clin Nutr. 2006 Nov;84(5):1200-7. Ito Y, Suzuki K, Ishii J, Hishida H, et al. A population-based follow-up study on mortality from cancer or cardiovascular disease and serum carotenoids, retinol and tocopherols in Japanese inhabitants. Asian Pac J Cancer Prev. 2006 Oct-Dec;7(4):533-46. Walston J, Xue Q, Semba RD, Ferrucci L, Cappola AR, Ricks M, Guralnik J, Fried LP. Serum antioxidants, inflammation, and total mortality in older women. Am J Epidemiol. 2006 Jan 1;163(1):18-26. Jatoi A, Williams BA, Marks R, Nichols FC, Aubry MC, Wampfler J, Yang P. Exploring vitamin and mineral supplementation and purported clinical effects in patients with small cell lung cancer: results from the Mayo Clinic lung cancer cohort. Nutr Cancer. 2005;51(1):7-12. Buijsse B, Feskens EJ, Schlettwein-Gsell D, Ferry M, Kok FJ, Kromhout D, de Groot LC. 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 Oct;82(4):879-86. Kirsh VA, Hayes RB, Mayne ST, Chatterjee N, Subar AF, Dixon LB, Albanes D, Andriole GL, Urban DA, Peters U; PLCO Trial. Supplemental and dietary vitamin E, beta-carotene, and vitamin C intakes and prostate cancer risk. J Natl Cancer Inst. 2006 Feb 15;98(4):245-54. Shetty PS, Breeze E, Fletcher AE. Antioxidant vitamins and mortality in older persons: findings from the nutrition add-on study to the Medical Research Council Trial of Assessment and Management of Older People in the Community. Am J Clin Nutr. 2003 Nov;78(5):999-1010. Losonczy KG, Harris TB, Havlik RJ. Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly. Am J Clin Nutr. 1996 Aug;64(2):190-6. Daviglus ML, Orencia AJ, Dyer AR, Liu K, Morris DK, Persky V, Chavez N, Goldberg J, Drum M, Shekelle RB, Stamler J. Dietary vitamin C, beta-carotene and 30-year risk of stroke: results from the Western Electric Study. Neuroepidemiology. 1997;16(2):69-77. Blot WJ, Li JY, Taylor PR, Guo W, Dawsey SM, Li B. The Linxian trials: mortality rates by vitamin-mineral intervention group. Am J Clin Nutr. 1995 Dec;62(6 Suppl):1424S-1426S. Blot WJ, Li JY, Taylor PR, Guo W, Dawsey S, Wang GQ, Yang CS, Zheng SF, Gail M, Li GY, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst. 1993 Sep 15;85(18):1483-92. Fawzi WW, Msamanga GI, Spiegelman D, Wei R, Kapiga S, Villamor E, Mwakagile D, Mugusi F, Hertzmark E, Essex M, Hunter DJ. A randomized trial of multivitamin supplements and HIV disease progression and mortality. N Engl J Med. 2004 Jul 1;351(1):23-32. Rahmathullah L, Underwood BA, Thulasiraj RD, Milton RC, Ramaswamy K, Rahmathullah R, Babu G. Reduced mortality among children in southern India receiving a small weekly dose of vitamin A. N Engl J Med. 1990 Oct 4;323(14):929-35. Jatoi A, Daly BD, Kramer G, et al. A cross-sectional study of vitamin intake in postoperative non-small cell lung cancer patients. J Surg Oncol. 1998 Aug;68(4):231-6. Pastorino U, Infante M, Maioli M, Chiesa G, Buyse M, Firket P, Rosmentz N, Clerici M, Soresi E, Valente M, et al. Adjuvant treatment of stage I lung cancer with high-dose vitamin A. J Clin Oncol. 1993 Jul;11(7):1216-22. Nathens AB, Neff MJ, Jurkovich GJ, Klotz P, Farver K, Ruzinski JT, Radella F, Garcia I, Maier RV. Randomized, prospective trial of antioxidant supplementation in critically ill surgical patients. Ann Surg. 2002 Dec;236(6):814-22. http://www.newsvine.com/_news/2007/02/27/589608-antioxidants-dont-help-you-live-longer http://oregonstate.edu/dept/ncs/newsarch/2007/Feb07/vitaminstudy.html http://www.washingtonpost.com/wp-dyn/content/article/2007/02/27/AR2007022700925.html

------- Another abstract by Dr. Bjelakovic:

Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis

Summary Background Oxidative stress can cause cancer. Our aim was to establish whether antioxidant supplements reduce the incidence of gastrointestinal cancer and mortality. Methods With the Cochrane Collaboration methodology, we reviewed all randomised trials comparing antioxidant supplements with placebo for prevention of gastrointestinal cancers. We searched electronic databases and reference lists (February, 2003). Outcome measures were incidence of gastrointestinal cancers, overall mortality, and adverse effects. Outcomes were analysed with fixed-effect and random-effects model meta-analyses and were reported as relative risk with 95% CIs. Findings We identified 14 randomised trials (n=170 525). Trial quality was generally high. Heterogeneity of results was low to moderate. Neither the fixed-effect (relative risk 0·96, 95% CI 0·88–1·04) nor random-effects meta-analyses (0·90, 0·77–1·05) showed significant effects of supplementation with β-carotene, vitamins A, C, E, and selenium (alone or in combination) versus placebo on oesophageal, gastric, colorectal, pancreatic, and liver cancer incidences. In seven high-quality trials (n=131 727), the fixed-effect model showed that antioxidant significantly increased mortality (1·06, 1·02–1·10), unlike the random-effects meta-analysis (1·06, 0·98–1·15). Low-quality trials showed no significant effect of antioxidant supplementation on mortality. The difference between the mortality estimates in high-quality and low-quality trials was significant (Z=2·10, p=0·04 by test of interaction). β-carotene and vitamin A (1·29, 1·14–1·45) and β-carotene and vitamin E (1·10, 1·01–1·20) significantly increased mortality, whereas β-carotene alone only tended to increase mortality (1·05, 0·99–1·11). In four trials (three with unclear or inadequate methodology), selenium showed significant beneficial effect on the incidence of gastrointestinal cancer. Interpretation We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers on the contrary, they seem to increase overall mortality. The potential preventive effect of selenium should be studied in adequate randomised trials.

'Aging, Brain Inflammation and Behavior'

Thought this was interesting in relation to DS, although he doesn't mention it. Alot of people with DS have weak immune systems, which leads to being sick alot, at times. This could have something to do with their cognition. We already know that inflammation is an issue with people with DS. I've emailed the professor who talks about this and asked him for the name of the study which is being talked about below.

http://media.www.dailyvidette.com/media/storage/paper420/news/2007/02/05/News/Professor.Presents.aging.Brain.Inflammation.And.Behavior-2695013.shtml

Professor presents 'Aging, Brain Inflammation and Behavior'

Kristi Kawanna

Rodney Johnson presented a seminar "Aging Brain Inflammation and Behavior" on Feb. 2. Hosting the seminar was the department of biological sciences and Phi Sigma.Johnson came to ISU from the University of Illinois, where he is an integrative immunology and behavior professor. Johnson has also authored over 78 publications. "It is interesting to think about the interaction between the immune system and the brain. Ten years ago people may not have even thought there was such an interaction, but today that is not the case. Remember that the brain does not have a way to detect infection pathogens, but when we are sick we change our behavior, motivating us to act differently than when we are well. I call this the sickness behavior syndrome," Johnson said. After a brief introduction of his study, Johnson began to explain the basis of his research. "You begin with an infectious pathogen. A macrophage encounters the infection and produces inflammatory cytokines in the brain. These cytokines cause behavior response," Johnson said. Behavior responses include food intake, spatial working memory deficits, slow wave sleep, lethargy, cognitive and motor deficits, depression, decreased social behavior and anorexia. Johnson then discussed the importance of Lipopolysaccharide and sickness behavior. Part of the research Johnson has done to understand this concept, has been performed on older rats. A rat injected with increased LPS showed a difference in behavior than a rat that wasn't affected by the LPS. Johnson explained the brain forms a representation of the peripheral innate immune system response. The representation is at the origin of sickness behavior and is cytokine based. "It's important to keep in mind that sickness behavior is normally adaptive and fully reversible. Georges Canguilhem once said 'To be healthy is to be able to be ill and recover from it.' Sickness behavior is a normal part of life," Johnson said. Johnson also discussed the fact that ongoing brain pathology "primes" microglia (primary stimulus) and that peripheral infection further activates microglia (secondary stimulus). This information is used in studying diseases such as Multiple Sclerosis and Alzheimer's disease. Also discussed at the seminar were the effects LPS and cytokines have on the elderly. "We need to understand what makes some individuals not recover completely when they get well. This is especially true of the elderly. An infection in an elderly person can lead to cognitive impairment. This then leads to diminished self care such as weight loss, anorexia and the fact that they will be less likely to visit an out-patient clinic. Once self-care begins to diminish, more hospitalization is needed and the mortality rate goes up," Johnson said.
At the end of the seminar, guests were encouraged to ask questions. The topics of inflammatory drugs in relation to fevers and whether or not inflammation and depression are related were discussed. "In regards to whether or not inflammatory drugs should be taken to reduce fever is a topic that is being looked at carefully in the medical world. I was surprised last year when I came across an article by the American Nurses Association that discussed the benefits of fever. As long as a fever isn't too high, inflammatory drugs aren't always needed as long as the fever is monitored," Johnson said. "There is a strong link between inflammation of the brain and depression. Anytime there is an increase in inflammation, there can be a disruption in serotonin, which can lead to higher levels of depression," Johnson said. Johnson also said anytime there is tissue trauma, inflammation is the response, which can lead to post surgical cognitive disorder. "I thought the seminar was very interesting. Everything was new information to me, but it made sense. Johnson was a good speaker who kept the information entertaining. He also brought the information down to a basic level so it was easier to understand," Kelly Slattery, biology graduate student, said.

Antioxidant Supplements . . .

This is a study that just came out. The abstract is below this WebMD article. I find this rather hard to believe. I've emailed the doctor who did the study and asked him for the full text of it - I would like to see what studies he looked at to base his conclusion on. There are so many studies on Vitamin E in particular that show it helps with AD and reducing oxidative stress, etc. I am looking into alot of things here and will post what I find.

Antioxidant Supplements Raise Death Risk

Feb 26, 2007
--------------------------------------------------------------------------------
(WebMD) Use of the popular antioxidant supplements beta-carotene, vitamin E, or vitamin A slightly increases a person's risk of death, an overview of human studies shows.

The study also shows no benefit — and no harm — for vitamin C supplements.
Selenium supplements tended to very slightly reduce risk of death.

Oxidative stress — caused by highly reactive "free radical" compounds circulating in the blood — is a factor in most diseases.

Antioxidants sweep up these free radicals. It seems to be a no-brainer that
taking antioxidant supplements would protect your health. But it may not be
that simple.

A new, detailed analysis of human studies of beta-carotene, vitamin A, and
vitamin E shows that people who take these antioxidant supplements don't live any longer than those who don't take them. In fact, those who take the
supplements have an increased risk of death.

The finding, reported in The Journal of the American Medical
Association, comes from Goran Bjelakovic, M.D., DrMedSci, of the University of Nis in Serbia; Christian Gluud, M.D., DrMedSci, of Copenhagen University Hospital in Denmark; and colleagues.

"Our findings have already changed the way I counsel my patients about
antioxidant supplements," Bjelakovic tells WebMD in an email interview.
"According to our findings, beta-carotene, vitamin A, and vitamin E cannot
be recommended. I am telling them that they should stop using these
supplements."

"There is no reason to take anything that hasn't been proven beneficial.
And these antioxidant supplements do not seem beneficial at all," Gluud
tells WebMD.

Not everyone agrees. Nutritionist Andrew Shao, Ph.D., is vice president for
scientific and regulatory affairs at the Council for Responsible Nutrition, a supplement-industry trade group.

"Consumers can feel confident in relying on their antioxidant supplements as they always have," Shao tells WebMD. "They can continue
to take them knowing they will provide the same benefits — and this article
does not change that."

Antioxidant Supplements and Death Risk

Bjelakovic, Gluud, and colleagues analyzed data from 68 randomized clinical
trials of antioxidant supplements that included 232,606 people. When they
looked at all the trials together, they found that the supplements offered no benefit but did no harm.

However, some of the trials were more exactly controlled than others. There
were 21 trials that had a "high bias risk." These trials had one or more problems with randomizing study participants to the supplement or placebo groups, with blinding both the participants and the investigators to whether
participants received supplements or placebos, and/or with following up on all participants until the end of the study.

So the researchers looked only at the 47 "low-bias-risk" studies — which included nearly 181,000 participants and which did not include people
taking selenium. They found that:


Taking vitamin A supplements increased the risk of death by 16 percent

Taking beta-carotene supplements increased the risk of death by 7 percent

Taking vitamin E supplements increased the risk of death by 4 percent

Taking vitamin C supplements did not have any effect on risk of death
Shao says it just isn't fair to study antioxidants in this way.

"What these authors have done is combine studies that are incredibly
dissimilar in all sorts of ways," he says. "These studies looked at
different nutrients at different doses at different durations with different
lengths of follow-up — and in different populations, ranging from folks who
were incredibly healthy to people with cancer and other diseases."

Moreover, Shao says, the researchers looked only at studies in which people
died. That left out 405 clinical trials, which he says skews the results in
favor of death risk. And he points out that the researchers original 68 studies did not show any harm from supplements.

"These questions cause one to step back and wonder if the findings are
relevant to the healthy population that uses these supplements to maintain
healtand avoid chronic disease," Shao says. "That is a point they
don't make: that antioxidants are not used to treat cancer or heart disease.
They are used for disease prevention."

Edgar R. Miller III, M.D., Ph.D., associate professor of medicine at Johns
Hopkins University, in 2004 analyzed clinical trials of vitamin E. He found
that high doses of vitamin E did more harm than good. Miller has high praise
for the Bjelakovic/Gluud study.

"This is a great study. It is the highest form of scientific evidence," Miller tells WebMD. "I don't think that [Shao's] criticism
is legitimate. I argue this is the best technique to analyze all this
information."

Gluud and Bjelakovic strongly disagree that they "cherry picked"
only studies that fit some preconceived conclusion. They point out that all of their methods are "transparent" and open to public view.

"Anyone is welcome to criticize our research," Gluud says. "But
my question is, what is your evidence? I think the parties that want to sell or use these antioxidant supplements in the dosages used in these trials, they want [to see only] positive evidence that it works beneficially."

Advice to Consumers

Kathleen Zelman, MPH, R.D., L.D., is director of nutrition for WebMD. She
reviewed the Bjelakovic/Gluud study for this article.

"This is a very comprehensive, to-be-respected analysis. This isn't just
another study coming out," Zelman says. "The bottom line is that
antioxidant supplements are not a magic bullet for disease prevention. We hoped maybe they were, but they are not."

If you are interested in protecting your health, Zelman says, pills aren't
the answer.

"There is no single food or nutrient that is going to be the answer. The
secret really is lifestyle," she says. "And the most important things
about lifestyle are being at a healthy weight, being physically active, and
eating a healthy diet."

Shao says he's not persuaded to stop taking antioxidant supplements.

"I take antioxidant supplements every day," he says. "I know
more about these nutrients than most people do, including the authors of this study, who are not nutritionists. This does not change a thing for me. You can take that to the bank."

Zelman has this advice: If you plan to continue taking antioxidant supplements, don't exceed the recommended daily doses.

"For nutritional insurance, my suggestion would be a once-daily
multivitamin," she says. "But for those people who take multiple
supplements, and are going to continue to do so, heed the warning and be sure to respect the safe upper dosage limits."

"If you are in doubt, take the time and go to your doctor and talk with
her or him," Gluud advises.

------------------------

Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention
Systematic Review and Meta-analysis

Goran Bjelakovic, MD, DrMedSci; Dimitrinka Nikolova, MA; Lise Lotte Gluud, MD, DrMedSci; Rosa G. Simonetti, MD; Christian Gluud, MD, DrMedSci

JAMA. 2007;297:842-857.

Context Antioxidant supplements are used for prevention of several diseases.

Objective To assess the effect of antioxidant supplements on mortality in randomized primary and secondary prevention trials.

Data Sources and Trial Selection We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium either singly or combined vs placebo or vs no intervention were included in our analysis. Randomization, blinding, and follow-up were considered markers of bias in the included trials. The effect of antioxidant supplements on all-cause mortality was analyzed with random-effects meta-analyses and reported as relative risk (RR) with 95% confidence intervals (CIs). Meta-regression was used to assess the effect of covariates across the trials.

Data Extraction We included 68 randomized trials with 232 606 participants (385 publications).

Data Synthesis When all low- and high-bias risk trials of antioxidant supplements were pooled together there was no significant effect on mortality (RR, 1.02; 95% CI, 0.98-1.06). Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.05-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality.

Conclusions Treatment with beta carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study.

Author Affiliations: The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Center for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Bjelakovic, L. L. Gluud, Simonetti, and C. Gluud and Ms Nikolova); Department of Internal Medicine, Gastroenterology and Hepatology, University of Nis, Nis, Serbia (Dr Bjelakovic); and Divisione di Medicina, Ospedale V. Cervello, Palermo, Italy (Dr Simonetti).