Dietary supplements

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.

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.

There have been mixed findings about the benefits of DHA (an omega-3 fatty acid), but in a study involving 485 older adults (55+) with age-related cognitive impairment, those randomly assigned to take DHA for six months improved the score on a visuospatial learning and episodic memory test. Higher levels of DHA in the blood correlated with better scores on the paired associate learning task. DHA supplementation was also associated with better verbal recognition, but not better working memory or executive function.

Other research has found no benefit from DHA to those already with Alzheimer’s, although those with Alzheimer’s tend to have lower levels of DHA in the blood. These findings reinforce the idea that the benefit of many proactive lifestyle strategies, such as diet and exercise, may depend mainly on their use before systems deteriorate.

The daily dose of algal DHA was 900 mg. The study took place at 19 clinical sites in the U.S., and those involved had an MMSE score greater than 26.

A two-year study involving 271 older adults (70+) with mild cognitive impairment has found that the rate of brain atrophy in those taking folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), was significantly slower than in those taking a placebo, with those taking the supplements experiencing on average 30% less brain atrophy. Higher rates of atrophy were associated with lower cognitive performance. Moreover those who with the highest levels of homocysteine at the beginning of the trial benefited the most, with 50% less brain shrinkage. High levels of homocysteine are a risk factor for Alzheimer’s, and folate, B12 and B6 help regulate it.

The finding that atrophy can be slowed in those with MCI offers hope that the treatment could delay the development of Alzheimer’s, since MCI is a major risk factor for Alzheimer’s, and faster brain atrophy is typical of those who go on to develop Alzheimer’s.

A European trial involving 225 patients with mild Alzheimer's has found that those who drank Souvenaid (a cocktail of uridine, choline and the omega-3 fatty acid DHA, plus B vitamins, phosopholipids and antioxidants) for 12 weeks were more likely to improve their performance in a delayed verbal recall task. 40% of the Souvenaid group showed improved performance compared to 24% of the placebo group. Those with the mildest cases of Alzheimer’s showed the most improvement. There was no improvement on the more general ADAS-cog test. Three further clinical trials, one in the U.S. and two in Europe, are now underway.

Scheltens, P. et al. 2010. Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial. Alzheimer's & Dementia, 6 (1), 1-10.

The nutrient choline is known to play a critical role in memory and brain function by positively affecting the brain's physical development through increased production of stem cells (the parents of brain cells). New research demonstrates that this occurs through the effect of choline on the expression of particular genes. The important finding is that diet during pregnancy turns on or turns off division of stem cells that form the memory areas of the brain. Developing babies get choline from their mothers during pregnancy and from breast milk after they are born. Other foods rich in choline include eggs, meat, peanuts and dietary supplements. Breast milk contains much more of this nutrient than many infant formulas. Choline is a vitamin-like substance that is sometimes treated like B vitamins and folic acid in dietary recommendations.A choline food database is available at:

A study has found that gerbils given a ‘cocktail’ of DHA, uridine and choline performed significantly better on learning and memory tests than untreated gerbils, and their brains had up to 70% more phosphatides (a type of molecule that forms cell membranes) than controls, suggesting that new synapses are forming. Some of the gerbils received all three compounds and some received only two; the improvements were greatest in those given all three. An earlier study had found that the treatment improved function in rats with cognitive impairment. Omega-3 fatty acids are found in fish, eggs, flaxseed and meat from grass-fed animals. Choline is found in meats, nuts and eggs. Uridine cannot be obtained from food sources, but is a component of human breast milk and can be produced in the body.

A mouse study has found that the diet of a pregnant mother, especially in regards to choline, can change the epigenetic switches that control brain development in the fetus. Pregnant mice received different diets during the period when a fetus develops its hippocampus. The genetic changes affected neurogenesis. The findings add to other research pointing to the effects of maternal diet on fetal development. Top sources of choline are eggs and meat. Fish and soy are also good sources.

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.