Dietary Supplements and Cognitive Function, Dementia, and Alzheimer’s Disease: What the Science Says

• A large, placebo-controlled, randomized clinical trial studying the well-characterized ginkgo product EGb-761 in more than 3,000 older adults found it ineffective in lowering the overall incidence of dementia and Alzheimer’s disease. Further analysis of the same data also found ginkgo to be ineffective in slowing cognitive decline, lowering blood pressure, or reducing the incidence of hypertension.
• A 2020 meta-analysis of 7 randomized controlled trials involving 939 patients with Alzheimer’s disease found that those given Ginkgo biloba extract EGb-761 had some improvement in cognitive function. Treatments varied within the studies from 120, 160, and 240 mg/day, and duration ranged from 3 months to 26 weeks. The analysis of effects on daily life found no difference between ginkgo biloba preparation and placebo. 
• However, a 2015 systematic review and meta-analysis involving a total of 2,561 participants concluded that Ginkgo biloba EGb-761 at 240 mg/day stabilized or slowed decline in cognition, function, behavior, and global change at 22 to 26 weeks in cognitive impairment and dementia, especially for people with neuropsychiatric symptoms.
• Another 2016 systematic review and meta-analysis of 21 randomized controlled trials involving 2,608 participants concluded that Ginkgo biloba is potentially beneficial for improving cognitive function, activities of daily living, and global clinical assessment in people with mild cognitive impairment or Alzheimer’s disease; however, because of small sample size, inconsistent findings and methodological quality of studies included in the review, more research is need to confirm the effectiveness and safety of Ginkgo biloba for the treatment of cognitive impairment and Alzheimer’s disease.

• Side effects of ginkgo supplements may include headache, nausea, gastrointestinal upset, diarrhea, dizziness, or allergic skin reactions. More severe allergic reactions have occasionally been reported. There are some data to suggest that ginkgo can increase bleeding risk.

• Among the nutritional and dietary factors studied to prevent cognitive decline in older adults, the most consistent positive research findings are for omega-3 fatty acids, often measured as how much fish people consumed. However, a 2016 Cochrane review of 3 randomized, placebo-controlled trials involving a total of 632 participants found no convincing evidence for the efficacy of omega-3 polyunsaturated fatty acid supplements in the treatment of mild-to-moderate Alzheimer’s disease. The result was consistent for all outcomes relevant for people with dementia.
• A 2020 systematic review and meta-analysis of 38 randomized controlled trials with a total of 49,757 participants assessed effects of higher vs lower omega-3, omega-6, or total polyunsaturated fats and outcomes on new neurocognitive illness, new cognitive impairment, or global cognition. The reviewers concluded that long-chain omega-3 probably has little or no effect on new neurocognitive outcomes or cognitive impairment and noted that the effects of increasing α-linolenic acid, omega-6, or total polyunsaturated fatty acid were unclear.
• Further, a 2012 Cochrane review of 3 randomized controlled trials involving more than 3,500 participants concluded that available evidence shows no benefit of omega-3 supplementation on the cognitive functioning of older people without dementia.

• Omega-3 fatty acid supplements usually do not have negative side effects. When side effects do occur, they typically consist of minor gastrointestinal symptoms. 

Many laboratory and animal studies have investigated the role of vitamin E in the prevention and treatment of Alzheimer’s disease; evidence from human studies is much more limited.

• A 2017 Cochrane review of 2 randomized controlled trials involving a total of 820 participants with either mild cognitive impairment or Alzheimer’s disease found no evidence that the alpha-tocopherol form of vitamin E given to people with mild cognitive impairment prevents progression to dementia, or that it improves cognitive function in people with mild cognitive impairment or dementia due to Alzheimer’s disease. However, there is moderate quality evidence from a single study that it may slow functional decline in Alzheimer’s disease. The researchers noted that these findings are still based on small numbers of trials and participants and further research is quite likely to affect the results.
• A 2021 systemic review and meta-analysis of 5 cohort studies and 3 randomized controlled trials involving a total of 14, 262 participants analyzed the effects of vitamin E on the risk of developing Alzheimer’s disease as well as its effects on progression of Alzheimer’s. Researchers were not able to find conclusive evidence on the association or correlation between vitamin E and Alzheimer’s disease.

• Research has not found any adverse effects from consuming vitamin E in food. However, high doses of alpha-tocopherol supplements can cause hemorrhage and interrupt blood coagulation in animals, and in vitro data suggest that high doses inhibit platelet aggregation.
• Results from the Selenium and Vitamin E Cancer Prevention (SELECT) Trial suggest that vitamin E supplements (400 IU/day) may increase the risk of prostate cancer. Follow-up studies exploring this finding are underway.
• Vitamin E supplements have the potential to interact with several types of medications, including anticoagulant and antiplatelet medications, simvastatin and niacin, and chemotherapy and radiotherapy.

A few preliminary clinical studies exploring the effects of curcumin on Alzheimer’s disease have been conducted.

• A 2019 systematic review found that preclinical studies have demonstrated beneficial effects of curcumin on cognition in Alzheimer’s disease. However, results of clinical trials are less consistent. Preliminary evidence from clinical studies suggests that curcumin may prevent cognitive decline in healthy populations, but the reviewers stated that more research to improve curcumin’s bioavailability is crucial and more human trials examining curcumin’s cognitive-enhancing effect are necessary.
• A 2016 randomized, placebo-controlled trial involving 96 community-dwelling, cognitively healthy, older adults found that curcumin had limited influence on cognitive function, mood, or general quality of life over 12 months. The researchers concluded that additional longitudinal studies are warranted to determine whether curcumin can slow neurodegeneration leading to cognitive decline and Alzheimer’s disease.

• Curcumin is considered safe for most adults, but high doses or long-term use may cause indigestion, nausea, or diarrhea.
• In animals, very high doses of curcumin have caused liver problems. No cases of liver problems have been reported in people.

• A 2018 Cochrane systematic review of 5 trials involving 879 participants concluded that there is no evidence for beneficial effects on cognition of supplementation with B vitamins for 6 to 24 months. The reviewers also noted that evidence from one study of a reduced rate of brain atrophy in participants taking B vitamins and a beneficial effect of B vitamins on episodic memory in those with higher plasma homocysteine (tHcy) at baseline warrants attempted replication.
• A 2022 meta-analysis of 95 studies lasting 12 months or more with 46,175 participants suggests that B vitamin supplementation may slow cognitive decline, especially in populations who received early intervention and long-term intervention. The reviewers also noted that higher intake of dietary folate, but not B12 or B6, may be associated with a reduced risk of incident dementia in non-dementia aged population.

• No adverse effects have been associated with excess vitamin B12 intake from food and supplements in healthy individuals. However, vitamin B12 has the potential to interact with certain medications. In addition, several types of medications might adversely affect vitamin B12 levels, including proton pump inhibitors, chloramphenicol, H2 receptor antagonists, and metformin.
• High intakes of vitamin B6 from food sources have not been reported to cause adverse effects. However, chronic administration of 1 to 6 g oral pyridoxine per day for 12 to 40 months can cause severe and progressive sensory neuropathy characterized by ataxia (loss of control of bodily movements). Symptom severity appears to be dose dependent, and the symptoms usually stop if the patient discontinues the pyridoxine supplements as soon as the neurologic symptoms appear. Other effects of excessive vitamin B6 intakes include painful, disfiguring dermatological lesions; photosensitivity; and gastrointestinal symptoms, such as nausea and heartburn.