Dietary supplements for Alzheimer’s disease: are there any effective ones?

Virtually all clinical trials of Alzheimer’s medications have failed in the last 15 years. Drugs ranging from antibodies to neurochemical enhancers did not make it to the pharmacies. However, plenty of food supplements are on the shelf at the pharmacy, some promising to “support your memory and brain function,” “protect from oxidative stress,” and even “reduce your risk of dementia.” No doubt a healthy diet goes a long way toward promoting good health, but can the right diet or dietary supplements alleviate the risk or improve the symptoms of Alzheimer’s disease? We are going to put together a series of articles to take a closer look at popular supplements. Today, we will discuss three of the most popular supplements for memory – omega-3 fatty acids (commonly called fish oil), Ginkgo biloba extract, and vitamin E.

Fish oil was approved by the FDA to control high triglyceride levels in 2019. At lower doses, fish oil is used as a dietary supplement and like most supplements does not require a prescription. According to Healthline.com, omega-3 fatty acids, found in fish oil, “can fight age-related mental decline and Alzheimer’s disease.” Big claims like that are easy to make, but hard to prove with solid science. According to one large analysis, most studies did not find any statistically significant effect of omega-3 fatty acids against Alzheimer’s disease.1 While shorter trials in the analysis may overlook long-term effects, a 3-year-long trial confirmed that omega-3 fatty acids are not effective against cognitive decline in the long term.2 Moreover, omega-3 fatty acids might struggle to reach the brain,3 needing administration of higher doses to have a sufficient concentration there. However, higher doses mean a higher risk of side effects. A meta-analysis with a total of 24.5 thousand participants shows that omega-3 fatty acids had some adverse effects, even though it is generally well-tolerated.4 All in all, its dubious efficacy and risk of side effects do not support omega-3 supplementation as a treatment of Alzheimer’s disease.

Instead of taking omega-3 fatty acid supplements, a better approach is to incorporate fish into your diet regularly, particularly those rich in healthy fats (like salmon, herring, cod, or mackerel). If you are a vegetarian, Brussels sprouts and walnuts are good choices. However, omega-3 fatty acids in seed oils, such as flaxseed oil, have poor bioavailability, which greatly reduces its omega-3 effects.

Ginkgo biloba extract is a plant-based food supplement that comes from trees native to China. It is marketed as a cognitive enhancer for age-related neurodegenerative disorders such as Alzheimer’s disease. The active compounds in Ginkgo biloba extract are believed to dilate blood vessels and thus increase blood supply to the brain. However, a comprehensive analysis of the effect of Ginkgo biloba on Alzheimer’s disease concluded there was no significant difference with the placebo group,5 despite numerous claims of positive effects on cognitive function in other reports.6 7 Most “positive” studies of Ginkgo’s effect on memory are limited due to low quality of the evidence. Almost all studies agree that Ginkgo biloba extract supplementation is safe with very few side effects. Overall, while Ginkgo biloba extract is safe, there is no robust evidence to believe that it helps at all with dementia.

Lastly, vitamin E is another common food supplement often used against cognitive decline. Vitamin E is a fat-soluble antioxidant that detoxifies oxygen radicals that are thought to drive cellular aging and contribute to Alzheimer’s disease. The three high-quality, large-scale clinical trials of vitamin E treatment – two for Alzheimer’s disease and one for mild cognitive impairment – found no significant improvement in cognitive measures.8,9,10 Importantly, the recommended daily allowance of vitamin E is around 22 international units, but the doses used in these studies were enormous – 2000 international units daily. At these doses, Vitamin E stops acting as antioxidants and may produce some toxicity. One large study found that a high dosage of these supplements (> 400 international units daily) may increase all-cause mortality.11 Thus, it is clear that very high doses of vitamin E are a bad idea, but whether modest doses could make a difference remains to be seen.

For all three supplements, fish oil, Ginkgo biloba extract, and vitamin E, there is no definitive evidence that they slow cognitive decline in Alzheimer’s disease. While Ginkgo biloba extract is pretty safe, both omega-3 fatty acids in fish oil and vitamin E have a risk of side effects, especially in higher doses. While a good diet takes some good effort, it generally outperforms food supplements in improving overall health with fewer side effects.

References:

References

  1. Canhada, S., Castro, K., Perry, I. S. & Luft, V. C. Omega-3 fatty acids’ supplementation in Alzheimer’s disease: A systematic review. Nutr. Neurosci. 21, 529–538 (2018).
  2. Andrieu, S. et al. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial. Lancet Neurol. 16, 377–389 (2017).
  3. Arellanes, I. C. et al. Brain delivery of supplemental docosahexaenoic acid (DHA): A randomized placebo-controlled clinical trial. EBioMedicine 59, 102883 (2020).
  4. Chang, C.-H. et al. Safety and tolerability of prescription omega-3 fatty acids: A systematic review and meta-analysis of randomized controlled trials. Prostaglandins Leukot. Essent. Fatty Acids 129, 1–12 (2018).
  5. Birks, J. & Grimley Evans, J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst. Rev. CD003120 (2009) doi:10.1002/14651858.CD003120.pub3.
  6. Yuan, Q., Wang, C., Shi, J. & Lin, Z. Effects of Ginkgo biloba on dementia: An overview of systematic reviews. J. Ethnopharmacol. 195, 1–9 (2017).
  7. Yang, G., Wang, Y., Sun, J., Zhang, K. & Liu, J. Ginkgo Biloba for Mild Cognitive Impairment and Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Curr. Top. Med. Chem. 16, 520–528 (2016).
  8. Dysken, M. W. et al. Effect of Vitamin E and Memantine on Functional Decline in Alzheimer Disease. JAMA J. Am. Med. Assoc. 311, 33–44 (2014).
  9. Sano, M. et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N. Engl. J. Med. 336, 1216–1222 (1997).
  10. Petersen, R. C. et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N. Engl. J. Med. 352, 2379–2388 (2005).
  11. Miller, E. R. et al. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann. Intern. Med. 142, 37–46 (2005).