Diet & supplements for Alzheimer's

Two years ago, I reported on a clinical trial of a nutrient cocktail called Souvenaid for those with early Alzheimer’s. The three-month trial, involving 225 patients, had some success in improving verbal recall, with those with the mildest level of impairment benefiting the most.

The ‘cocktail’, designed by a MIT professor of brain and cognitive science, includes choline, uridine and the omega-3 fatty acid DHA. Earlier research indicated that these nutrients — precursors to the lipid molecules that help make up neural membranes — need to be administered together to be effective. In animal studies, the cocktail increased the number of dendritic spines, which are reduced in Alzheimer’s disease.

A further trial of the supplement has now been reported on. This randomized, controlled double-blind study followed 259 patients with early Alzheimer’s for six months. The placebo group was given an iso-caloric control product. Compliance was high (around 97%), and no serious side effects occurred.

During the first three months, all patients improved their verbal memory performance, but after that those on placebo began to deteriorate, while those on Souvenaid continued to improve. Their performance at the end of the trial was significantly better than that of the placebo group. Moreover, brain scans showed that their brains began to show more normal activity patterns, consistent with the regaining of greater synaptic function.

Because the supplement only seems to be effective for those in the early stages (in this study, participants averaged around 25 on a scale of dementia that ranges from 1 to 30, with 30 being normal), a two-year trial is now underway with patients with MCI.

Scheltens, P. et al. 2012. Efficacy of Souvenaid in Mild Alzheimer’s Disease: Results from a Randomized, Controlled Trial. Journal of Alzheimer’s Disease, 31 (1), 225-36.

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 "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.

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.

http://www.eurekalert.org/pub_releases/2009-07/uosf-crm070109.php

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.

http://www.eurekalert.org/pub_releases/2008-11/uoc--vbr103008.php

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.

http://www.eurekalert.org/pub_releases/2008-04/aaon-vem040208.php

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.

http://www.eurekalert.org/pub_releases/2006-10/jaaj-ofa100506.php

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.

http://www.eurekalert.org/pub_releases/2006-04/miot-mro042706.php

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.

http://www.eurekalert.org/pub_releases/2005-11/asfb-ciw110305.php

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.

http://www.eurekalert.org/pub_releases/2005-04/nioa-cdo041205.php
http://www.eurekalert.org/pub_releases/2005-04/mc-dia041105.php

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 athttp://tinyurl.com/5bzbs

http://www.eurekalert.org/pub_releases/2004-12/potn-usn122804.php
http://www.sciencentral.com/articles/view.htm3?article_id=218392455

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.