Is there any evidence for the use of supplements in Alzheimer’s disease?

B vitamins

High levels of the amino acid homocysteine have been associated with a higher risk of Alzheimer’s disease.^[1] Because folic-acid, vitamin-b6, and vitamin-b12 play a central role in the metabolism of homocysteine, these vitamins have been extensively tested in clinical trials for their ability to improve cognitive function after the onset of Alzheimer’s disease, with the evidence as a whole indicating little-to-no benefit.

Vitamin D

A large body of evidence suggests the immune system facilitates Alzheimer’s disease.^[2] Given this, vitamin D, which can influence immune function, may have an effect on the disease. One clinical trial supports a beneficial effect of vitamin D supplementation in people with Alzheimer’s disease. Mendelian randomization trials have also found that having genetically higher vitamin D levels seems to lower the risk of developing Alzheimer’s disease.^[3][4]

Vitamin E

Oxidative stress, including oxidative damage to neuronal proteins and DNA, seems to occur during the development of Alzheimer’s disease.^[5][6] If this process contributes to the development and progression of Alzheimer’s disease, a viable intervention could be supplementing with vitamin E, a potent antioxidant. A few clinical trials have tested the effect of a very high dose of vitamin E on people with Alzheimer’s disease, with some mixed evidence of benefit, but vitamin E supplementation does not seem to prevent dementia or Alzheimer’s disease in at-risk people.

Omega-3 fatty acids

The human brain contains a large quantity of the LCn3 docosahexaenoic acid (DHA),^[7] making it a reasonable hypothesis that supplementing with DHA and its precursor, eicosapentaenoic acid (EPA), could benefit brain health. Additionally, experiments on rodent models of Alzheimer’s disease have provided support for a beneficial effect of LCn3s.^[8][9] Despite this, clinical trials looking at the effect of LCn3s among people with Alzheimer’s disease suggest no benefit. More research is needed to determine whether supplementation with omega-3 fatty acids can help prevent Alzheimer’s disease.

Alpha-GPC

Acetylcholine is a neurotransmitter involved in cognitive function, and reductions in its signaling contribute to some of the symptoms of Alzheimer’s disease. As a result, people with the disease are frequently prescribed medications called acetylcholinesterase inhibitors (AChEIs), which inhibit the breakdown of acetylcholine, thereby increasing its levels in synapses. AChEIs can modestly benefit symptoms of Alzheimer’s disease but do not slow progression of the disease itself.^[10]

L-Alpha glycerylphosphorylcholine, or alpha-GPC, is a choline-containing compound that is believed to better deliver choline to the brain, where it can be used for acetylcholine synthesis (acetylcholine is made from choline and a molecule called acetyl-CoA). Preliminary evidence from a few clinical trials suggests alpha-GPC is beneficial for people with Alzheimer’s disease.

Ginkgo biloba

Ginkgo biloba tree leaves, commonly known simply as ginkgo biloba, are often used as a dietary supplement and contain a variety of terpenoids (a type of plant metabolite) known as ginkgolides. Ginkgo biloba may increase cerebral blood flow,^[11] which could benefit brain health, and ginkgolides have shown some benefit in animal models of Alzheimer’s disease.^[12] Although several clinical trials indicate ginkgo biloba may be beneficial for Alzheimer’s, the data as a whole are somewhat inconsistent (with seemingly variable responses based on the test used) and often have serious shortcomings (e.g., poor distinction between Alzheimer’s disease and other dementia types). Ginkgo biloba does not seem to prevent Alzheimer’s disease.

Lion’s mane mushroom

It has been posited that Hericium erinaceus, commonly known as lion’s mane mushroom, benefits cognitive function, partly based on research suggesting it increases levels of nerve growth factor (NGF), a peptide important to the growth and survival of neurons. However, whether lion’s mane (or, more specifically, terpenoids called erinacines, found in lion’s mane) actually stimulates NGF remains a source of debate. Highly preliminary research from a few clinical trials indicates lion’s mane may be beneficial for people with or at risk of Alzheimer’s disease.

Panax ginseng

Panax ginseng (aka Asian ginseng, Chinese ginseng, Korean ginseng, or even just ginseng) is a plant whose roots are often used as a supplement. One component of panax ginseng, called gintonin, has been studied in animal models for its potential to inhibit amyloid beta toxicity^[13][14], making it a possible candidate for improving — or at least slowing — cognitive decline due to Alzheimer’s disease. Preliminary evidence from a few clinical trials suggests panax ginseng is beneficial for people with the disease.

Saffron

Saffron contains potentially bioactive compounds, including crocin, crocetin, and safranal, that experiments performed in rodent models suggest may be able to reduce the accumulation and toxicity of amyloid beta.^{[15][16][17][18]} Preliminary evidence from a few clinical trials suggests saffron is beneficial for Alzheimer’s disease.

Sodium oligomannate

Sodium oligomannate is a supplement (sold as GV-971) made from oligosaccharides (sugars) in a species of kelp called Ecklonia kurome. Some research suggests sodium oligomannate may reduce amyloid beta deposits in the brain (possibly via effects on the microbiome),^[19] and one trial by a company that sells a sodium oligomannate supplement found that it benefited cognition in people with Alzheimer’s disease.