Dietary supplements

No benefit in omega-3 supplements for cognitive decline

  • A large study of older adults with age-related macular degeneration found no cognitive benefit from taking omega-3 supplements, or supplements of lutein and zeaxanthin.

A large, five-year study challenges the idea that omega-3 fatty acids can slow age-related cognitive decline. The study, involving 4,000 older adults, was part of the Age-Related Eye Disease Study (AREDS), which established that daily high doses of certain antioxidants and minerals can help slow the progression of age-related macular degeneration. However, a follow-up study found the addition of omega-3 fatty acids to the AREDS formula made no difference.

Omega-3 fatty acids are believed to be responsible for the health benefits associated with regularly eating fish, which is associated with lower rates of AMD, cardiovascular disease, and possibly dementia.

In this study, participants from the AREDS study, all of whom had early or intermediate AMD, were randomly assigned to either omega-3, or lutein and zeaxanthin (nutrients found in large amounts in green leafy vegetables), or both, or a placebo. As they all had AMD, participants also took the AREDS formula, which includes vitamins C, E, beta carotene, and zinc. Cognitive testing took place at the beginning, at 2 years, and at 4 years.

There was no benefit to these supplements: all groups showed a similar rate of cognitive decline over the study period.

The researchers speculate that the failure to find a benefit may lie in the age of the participants — it may be that supplements, to be of benefit, need to be started earlier. The other possibility (and the one I myself give greater weight to, although both factors may well be influential) is that these nutrients need to be taken in food to be effective.

It should be noted that the omega-3 fatty acids taken were those found in fish, not those found in plant foods such as flaxseed, walnuts, soy products, and canola and soybean oils.



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Diet & supplements for Alzheimer's

Older news items (pre-2010) brought over from the old website

Caffeine reverses memory impairment in Alzheimer's mice

Consistent with earlier indications that moderate caffeine consumption may protect against memory decline, a study of genetically engineered mice has found that when the old mice began to show memory impairment, those given caffeine for 2 months performed as well as normal aged mice on cognitive tests, while those given plain drinking water continued to do poorly. The Alzheimer's mice received the equivalent of five 8-oz. cups of regular coffee a day (or two cups of Starbucks coffee, or 14 cups of tea). Moreover, the brains of the caffeinated mice showed nearly a 50% reduction in levels of beta amyloid. The effect appears to be through suppression of both β-secretase and presenilin 1 /g-secretase expression. Caffeine had this effect only on those with Alzheimer’s; normal mice given caffeine through adulthood showed no cognitive benefit.

Arendash, G.W. et al. 2009. Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-β Levels in Aged Alzheimer's Disease Mice. Journal of Alzheimer's Disease, 17 (3), 661-680.

Cao, C. et al. 2009. Caffeine Suppresses Amyloid-β Levels in Plasma and Brain of Alzheimer's Disease Transgenic Mice. Journal of Alzheimer's Disease, 17 (3), 681-697.

Vitamin B3 reduces Alzheimer's symptoms, lesions

High doses of nicotinamide, a form of vitamin B3, has been found to dramatically lower levels of tau protein in mice with Alzheimer's disease. The vitamin also increased proteins that strengthen microtubules, the scaffolding within brain cells along which information travels. Not only did the vitamin prevent memory loss in Alzheimer’s mice, it also slightly improved cognitive performance in normal mice. Nicotinamide is a water-soluble vitamin sold in health food stores. It generally is safe but can be toxic in very high doses. Clinical trials have shown it benefits people with diabetes complications and has anti-inflammatory properties that may help people with skin conditions. Clinical trials with Alzheimer’s patients are now underway.

Green, K.N. et al. 2008. Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau. Journal of Neuroscience, 28, 11500-11510.

Vitamin E may help Alzheimer's patients live longer

A study of 847 Alzheimer's patients has found that those who took 1,000 international units of vitamin E twice a day, were 26% less likely to die over a five-year period than people who didn't take vitamin E.  It also appears that taking vitamin E plus a cholinesterase inhibitor may be more beneficial than taking either agent alone.

The research was presented at the American Academy of Neurology Annual Meeting in Chicago, April 12 – April 19.

Omega-3 fatty acids may slow cognitive decline in some patients with very mild Alzheimer's disease

Several studies have shown that eating fish, which is high in omega-3 fatty acids, may protect against Alzheimer's disease. A Swedish study has now tested whether supplements could have similar effects. Patients with mild-to-moderate Alzheimer’s who took 1.7 grams of DHA and .6g of EPA showed the same rate of cognitive decline as those taking a placebo, however, among a subgroup of 32 patients with very mild cognitive impairment, those who took the fatty acids experienced less decline in six months compared with those who took placebo. It may be that anti-inflammatory effects are an important reason for the benefit, potentially explaining why effects were seen only in those with very early-stage disease, when levels of inflammation seem to be higher.

Freund-Levi;, Y. et al. 2006. w-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study: A Randomized Double-blind Trial. Archives of Neurology, 63, 1402-1408.

Dietary supplements offer new hope for Alzheimer's patients

A "cocktail" of dietary supplements (omega-3 fatty acids, uridine and choline) has been found to dramatically increase the amount of membranes that form brain cell synapses in gerbils. The treatment is now in human clinical trials. It is hoped that such treatment may significantly delay Alzheimer's disease. The treatment offers a different approach from the traditional tactic of targeting amyloid plaques and tangles. Choline can be found in meats, nuts and eggs, and omega-3 fatty acids are found in a variety of sources, including fish, eggs, flaxseed and meat from grass-fed animals. Uridine, which is found in RNA and produced by the liver and kidney, is not obtained from the diet, although it is found in human breast milk.

Wurtman, R.J., Ulus, I.H., Cansev, M., Watkins, C.J., Wang L. & Marzloff, G. 2006. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Research, Available online ahead of print 21 April 2006.

Compound in wine reduces levels of Alzheimer's disease-causing peptides

In cell studies, resveratrol has been found to lower levels of amyloid-beta peptides. Resveratrol is a natural compound occurring in abundance in grapes, berries and peanuts. The highest concentration has been reported in wines prepared from Pinot Noir grapes. The anti-amyloidogenic effect of resveratrol observed in cell cultures does not however necessarily mean that the beneficial effect can result simply from eating grapes or drinking wine. Further research aims to develop more active and more stable compounds.

Marambaud, P., Zhao, H. & Davies, P. 2005. Resveratrol Promotes Clearance of Alzheimer's Disease Amyloid- Peptides. Journal of Biological Chemistry, 280, 37377-37382.

Clinical diagnosis of Alzheimer's may be delayed with donepezil

In a study of people with mild cognitive impairment, those who took the drug donepezil were at reduced risk of progressing to a diagnosis of Alzheimer's during the first years of the trial, but by the end of the 3-year study there was no benefit from the drug. Of the 769 participants, 212 developed possible or probable Alzheimer’s within the 3-year study period; the donepezil group's risk of progression to a diagnosis of Alzheimer’s was reduced by 58% one year into the study, and 36% at 2 years, but no risk reduction at the end of three years. Vitamin E was also tested in the study and was found to have no effect at any point in the study.

Petersen, R.C. et al. 2005. Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment. New England Journal of Medicine, 352 (23), 2379-2388.

Pilot study points to healing power of turmeric

A study using genetically engineered mice has found that those mice on a diet rich in curcumin (the yellow pigment in the curry spice turmeric) developed 85% few Alzheimer’s plaques then the control group. Curcumin has antioxidant, anti-inflammatory, and cholesterol lowering properties, and has long been used in India as treatment for a variety of ailments. A human trial involving 33 Alzheimer's patients will soon commence.

Yang, F., Lim, G.P., Begum, A.N., Ubeda, O.J., Simmons, M.R., Ambegaokar, S.S., Chen, P.P., Kayed, R., Glabe, C.G., Frautschy, S.A. & Cole, G.M. 2004. Curcumin inhibits formation of Abeta oligomers and fibrils and binds plaques and reduces amyloid in vivo. Journal of Biological Chemistry, published online ahead of print December 7, 2004
A copy of the full paper can be found on the Journal of Biological Chemistry Web site at

Dietary supplement helps Alzheimer’s

A three-month study of 55 elderly patients with mild or moderate Alzheimer’s found that those given EV-1, a dietary supplement containing, among other things, the putative antioxidant ingredient of red wine, showed no deterioration during the trial. The supplement is designed to interfere with a defective mitochondrial cycle thought to contribute to the metabolic disturbances associated with late onset Alzheimer’s. The Krebs tricarboxylic acid cycle is fuelled by glucose and regulates levels of reactive oxygen species in the body. EV-1 contains glucose, a compound called malate that primes or maintains the Krebs cycle, and resveratrol - the antioxidant component of red wine that is thought to soak up reactive oxygen species. More studies are needed to confirm this result.

The findings were presented in November at the annual meeting of the Society for Neuroscience (SFN) in New Orleans.

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Link between fatty acids and heart disease complex

A meta-analysis of 72 studies with over 600,000 participants from 18 nations has concluded that total saturated fatty acid, whether measured in the diet or in the bloodstream as a biomarker, was not associated with coronary disease risk. Nor was there any significant association between consumption of total monounsaturated fatty acids, long-chain omega-3 and omega-6 polyunsaturated fatty acids, and cardiovascular risk.


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Dietary guidelines for choline may be insufficient

A study involving healthy men and women fed a baseline diet containing 550 mg choline/day (the adequate intake level set by the Institute of Medicine) for 10 days, then put on a low choline diet (50 mg choline/day) for up to 42 days, has found that the "right" amount of choline depends on many factors, including gender, age, and ethnicity.


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Calcium supplements not associated with increased cardiovascular risk in women

Contradicting some earlier studies, new research using data from the very large and long-running Nurses' Health Study has found that calcium supplement intake was not associated with a higher risk of cardiovascular disease in women.


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Pycnogenol improves cognition in college students in small trial

March, 2012

Another small study indicates that the plant extract Pycnogenol may improve working memory.

Back in 2008, I reported on a small study that found that daily doses of Pycnogenol® for three months improved working memory in older adults, and noted research indicating that the extract from the bark of the French maritime pine tree had reduced symptoms in children with ADHD. Now another study, involving 53 Italian university students, has found that cognitive performance improved in those taking 100 mg of Pycnogenol every day for eight weeks.

Students taking the supplement had higher scores on university exams than the control group, and they were apparently happier, less anxious, and more alert. It seems plausible that the improvement in academic performance results from working memory benefits.

The plant extract is an antioxidant, and benefits may have something to do with improved vascular function and blood flow in the brain.

However, the control group was apparently not given a placebo (I’m relying on the abstract and press release here, as this journal is not one to which I have access), they were simply “a group of equivalent students”. I cannot fathom why a double-blind, placebo procedure wasn’t followed, and it greatly lessens the conclusions of this study. Indeed, I wouldn’t ordinarily report on it, except that I have previously reported on this dietary supplement, and I am in hopes that a better study will come along. In the meantime, this is another small step, to which I wouldn’t give undue weight.


Luzzi R., Belcaro G., Zulli C., Cesarone M. R., Cornelli U., Dugall M., Hosoi M., Feragalli B. 2011. Pycnogenol® supplementation improves cognitive function, attention and mental performance in students. Panminerva Medica, 53(3 Suppl 1), 75-82.



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Dietary supplements

Older news items (pre-2010) brought over from the old website

Evidence mounts against DHEA use in treating cognitive decline

DHEA is a naturally-occurring hormone in the human body that declines with age. Previous research looking at the effect of DHEA supplementation on cognitive function and quality-of-life has produced inconsistent results. In the first long-term study (12 months) of healthy older adults, 110 men and 115 women aged 55-85 received either daily 50 mg doses of DHEA or a similar looking placebo pill for 1 year. It was found that, although youthful levels of DHEA were restored in the treatment group, the supplements had no benefits for cognitive function or quality-of-life in this representative sample.

[1222] Kritz-Silverstein, D., von Mühlen D., Laughlin G. A., & Bettencourt R.
(2008).  Effects of Dehydroepiandrosterone Supplementation on Cognitive Function and Quality of Life: The DHEA and Well-Ness (DAWN) Trial.
Journal of the American Geriatrics Society. 56(7), 1292 - 1298.

French maritime pine bark improves memory in elderly

A double-blind, placebo controlled, matched pairs study examined the effects of Pycnogenol (an antioxidant plant extract from the bark of the French maritime pine tree) on a range of cognitive and biochemical measures in 101 senior individuals aged 60-85 years old. Participants had a daily dose of 150mg for three months. Pycnogenol improved both numerical working memory as well as spatial working memory. Blood samples revealed that F2-isoprostanes significantly decreased with Pycnogenol, a sign of reduced oxidation of nerve membranes, suggesting that the antioxidant activity of Pycnogenol plays a major role for the clinical effects. Several recent research studies have found Pycnogenol reduced ADHD symptoms such as hyperactivity and improved attention, concentration and motor-visual coordination in children with ADHD. Pycnogenol extract has been studied for 35 years and is available in more than 600 dietary supplements.

[2425] Ryan, J., Croft K., Mori T., Wesnes K., Spong J., Downey L., et al.
(2008).  An examination of the effects of the antioxidant Pycnogenol(R) on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population.
J Psychopharmacol. 22(5), 553 - 562.

Long-term beta carotene supplementation may help prevent cognitive decline

A large, long-running study has found that men who took beta carotene supplements for 15 years or longer had significantly higher scores on several cognitive tests compared with men who took placebo. There was no such effect in those men who took the supplements for a year. The researchers suggest that although the benefits were modest in themselves, they may predict substantial differences in eventual risk of dementia. However, it should be noted that beta carotene is not without risks—for example, it may increase the risk of lung cancer in smokers — and that it would be premature to advise use of such supplements.

[710] Grodstein, F., Kang J H., Glynn R. J., Cook N. R., & Gaziano M. J.
(2007).  A Randomized Trial of Beta Carotene Supplementation and Cognitive Function in Men: The Physicians' Health Study II.
Arch Intern Med. 167(20), 2184 - 2190.

Dietary supplements improve old rats' memory and energy levels

After only a month, older rats fed two chemicals normally found in the body's cells and available as dietary supplements — acetyl-L-carnitine and an antioxidant, alpha-lipoic acid — performed better on memory tests, and had noticeably more energy (on a par with a “middle-aged” rat). It is thought that these chemicals act on the mitochondria, the “power-houses” of the cells. Mitochondria are increasingly being implicated as especially vulnerable to the aging process. Carnitine is a natural compound produced in the cell and obtained in the diet through meats and vegetables. It has been shown to improve balance and short-term memory in human. Lipoic acid is found in green, leafy vegetables.
The University of California has patented use of the combination of the two supplements to rejuvenate cells. Human clinical trials are currently underway.

[1215] Hagen, T. M., Liu J., Lykkesfeldt J., Wehr C. M., Ingersoll R. T., Vinarsky V., et al.
(2002).  Feeding acetyl-l-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress.
Proceedings of the National Academy of Sciences of the United States of America. 99(4), 1870 - 1875.

[618] Liu, J., Head E., Gharib A. M., Yuan W., Ingersoll R. T., Hagen T. M., et al.
(2002).  Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl-l-carnitine and/or R-α-lipoic acid.
Proceedings of the National Academy of Sciences of the United States of America. 99(4), 2356 - 2361.

[1232] Liu, J., Killilea D. W., & Ames B. N.
(2002).  Age-associated mitochondrial oxidative decay: Improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-l- carnitine and/or R-α-lipoic acid.
Proceedings of the National Academy of Sciences of the United States of America. 99(4), 1876 - 1881.

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