12 Best Supplements and Antioxidants for Dementia: An Evidence Review 2023

Alzheimer's disease is the most common cause of dementia in the UK.

Dementia is the name for a group of symptoms associated with an ongoing decline of brain functioning. It can affect memory, thinking skills and other mental abilities.

The exact cause of Alzheimer's disease is not yet fully understood, although a number of things are thought to increase your risk of developing the condition.

best supplements for dementia

These include:
  • increasing age
  • a family history of the condition
  • untreated depression, although depression can also be one of the symptoms of Alzheimer's disease
  • lifestyle factors and conditions associated with cardiovascular disease
There are currently no drugs available to prevent, treat, or reverse the course of Alzheimer’s disease. The five FDA-approved medications available for Alzheimer’s are designed to relieve symptoms such as memory loss, for a limited time — Aricept®, Exelon®, Namenda®, Namzaric® and Razadyne®.

There are more than 120 potential drugs in clinical trials now designed to treat the underlying causes of Alzheimer’s, rather than its symptoms. The ADDF (Alzheimer's Drug Discovery Foundation) has supported 20% of these, and many more ADDF-funded treatments are expected to be in human trials this year.

Best Anti Alzheimer's Strategies? 

The antioxidant connection is a hot area in Alzheimer’s research, but everyone agrees that more still needs to be done. Researchers aren’t sure if some antioxidants are better than others, and it’s possible that it might be better to get your antioxidants from food instead of from supplements.

Do Vitamins and Supplements Help With Alzheimer's?

We have compiled a list below together with their reference links. Note that this list is not exhaustive.

Methodology: The selection or short-listing of the list below is based on the available scientific evidence retrieved from scientific database such as PubMed and scientific search engine such as Google Scholar.

Here are the best natural supplements that are currently under research.

1. B Vitamins

Vitamins B6, B9 (folate) and B12 may be particularly important for supporting cognitive function as you age, and have been shown to play a major role in the development of dementia, including Alzheimer's disease, which is the most serious (and lethal).

A posthoc analysis study of the OmegAD trial, published in 2019, concluded that the effect of omega-3 supplementation on MMSE and CDR (measures of cognitive dysfunction) appears to be influenced by baseline tHcy (total homocysteine level), suggesting that adequate B vitamin status is required to obtain beneficial effects of omega-3-fatty acid on cognition.

2016 randomized controlled trial suggests that B vitamin supplementation slows cognitive decline in select groups, including people with mild cognitive impairment and high baseline homocysteine levels.

A 2016 study found that higher concentrations of docosahexaenoic acid (DHA) alone significantly enhanced the cognitive effects of B vitamins, while eicosapentaenoic acid (EPA) appeared less effective. When omega-3 fatty acid concentrations are low, B vitamin treatment has no effect on cognitive decline in MCI, but when omega-3 levels are in the upper normal range, B vitamins interact to slow cognitive decline.

2013 study took this research a step further, showing that not only do B vitamins slow brain shrinkage, but they specifically slow shrinkage in brain regions known to be most severely impacted by Alzheimer's disease. Moreover, in those specific areas the shrinkage is decreased by as much as 700% which is rather remarkable.

As in the previous study, participants taking high doses of folic acid and vitamins B6 and B12 lowered their blood levels of homocysteine, decreasing brain shrinkage by as much as 90%. Earlier research (2001) has also pointed out that even subclinical deficiencies in B vitamins may have "a subtle influence on aspects of cognitive performance."

2014 large meta-analysis of 11 trials did show that while B vitamins lowered homocysteine levels, they did not affect cognitive function.

Homocysteine levels are commonly high in people over 65 and are linked to strokes, coronary artery disease, and dementia. (2010 paper)

The good news is your body can eliminate homocysteine naturally, provided you're getting enough B9 (folate), B6 and B12. One study confirming this was published in 2010. Participants received either a placebo or 800 micrograms (mcg) of folic acid (the synthetic form of B9), 500 mcg of B12 and 20 mg of B6.

The study was based on the presumption that by controlling homocysteine levels you might be able to reduce brain atrophy, thereby slowing the onset of Alzheimer's. Indeed, after two years those who received the vitamin-B regimen had significantly less brain shrinkage compared to the placebo group. Those who had the highest levels of homocysteine at the start of the trial experienced brain shrinkage at half the rate of those taking a placebo.

Vitamin B3 and NAD

Since age is the greatest risk factor for Alzheimer's disease and dementia, supplements that slow aging-related processes may also slow progression of these diseases. An observational study found that older adults have lower levels of the coenzyme NAD+ in their brains than younger adults (Pubmed 2015).


2. DHA (Omega-3)

Docosahexaenoic acid (DHA) is a long-chain omega-3 polyunsaturated fatty acid found in some fish and over-the-counter supplements. It is a building block of the brain involved with numerous cellular pathways.

A posthoc analysis study of the OmegAD trial, published in 2019, concluded that the effect of omega-3 supplementation on MMSE and CDR (measures of cognitive dysfunction) appears to be influenced by baseline tHcy (total homocysteine level), suggesting that adequate B vitamin status is required to obtain beneficial effects of omega-3-fatty acid on cognition.

Studies (Pubmed 2016Pubmed 2018) have linked a low omega-3 index (below approximately 5 percent) with an increased risk of cognitive decline in older adults, linking a low omega index to brain shrinkage and cognitive impairment.

In preliminary reports from the MAPT (Multidomain Alzheimer Preventive Trial. 2014) study in 1680 older adults, 800 mg of DHA per day combined with physical activity, nutrition, and cognitive interventions led to improvements in cognition over 3 years. DHA alone resulted in less cognitive decline but only in people who had low levels of DHA at the start of the trial.

Some observational research studies found that people who eat fish every week (i.e., a major source of dietary DHA) or have higher DHA levels also had a lower risk of dementia or a slower rate of brain aging (Pubmed 2016).

Many governments recommend eating omega-3 containing fatty fish, two times per week. But that is often not enough. Ideally, people would need to eat fatty fish four times per week, while also supplementing with omega-3 fatty acids, at least 1,000 mg of pure omega-3 (DHA and EPA) per day.

Make sure you buy high-quality omega-3 fatty acid supplements, meaning that the omega-3 fatty acids are pure and have not oxidized much (having low “TOTOX” value).

TOTOX value stands for total oxidation value. The omega 3 fatty acids EPA and DHA from fish oil are highly sensitive to oxidation. This means that they are rapidly affected by contact with oxygen. Oxidised fatty acids are not beneficial to our health. For this reason, a good fish oil supplement has a low TOTOX value. The maximum TOTOX value is set at 26 by the Global Organization for EPA and DHA omega-3.

3. Melatonin 

Melatonin is neuro-protective. The brain consumes 20% of the body’s oxygen. All that oxygen passing through the brain makes a toxic byproduct called reactive oxygen species, which can damage nerves and blood vessels.
 
Is Melatonin Good For Alzheimer's?

Melatonin improves sleep, which could theoretically lead to long-term protection against Alzheimer's. A review and meta-analysis on melatonin treatment in Alzheimer's published in Neuroscience & Biobehavioral Reviews (Aug 2021) showed individuals with Alzheimer's improved with more than 12 weeks of treatment.
 
Your brain uses many different antioxidants, including melatonin, to neutralize the reactive oxygen species before they can cause harm. Therefore, it is not surprising that studies (2018) show melatonin seems to provide some protective effect against diseases like Alzheimer’s.

4. Gingko Biloba

Given that the ginkgo biloba tree is among the oldest trees in the world, ginkgo seeds have been used in traditional Chinese medicine and other types of treatment for thousands of years. The sole survivor of trees from 270 million years ago, it releases all its leaves in a golden explosion in just one day (Twitter).

Photo by Han Fei

In a 2016 study published in Nutrition, ginkgo biloba was shown to protect the brain from toxicity associated with aluminum chloride. Exposure to aluminum chloride has been linked to Alzheimer's and other cognitive impairments.

A 2012 study published in International Psychogeriatrics suggests ginkgo biloba may slow the aging process within mitochondria of your cells, which can affect the progression of Alzheimer’s.

There are two meta-analyses in dementia patients. In one analysis (2015), seven studies showed that patients using ginkgo had improved scores on certain cognitive performance tests. Two studies in the same analysis using different assessments, however, did not show a statistically significant difference (Ref). Another meta-analysis (2016) of patients with mild cognitive impairment and Alzheimer's disease showed that after 24 weeks of ginkgo, in combination with conventional medicine, they improved cognitive performance scores (Ref).

According to Cleveland Clinic (2002), an adult dose of 120 to 600 milligrams (mg) of ginkgo biloba per day seems to be effective for addressing memory problems. Some have suggested even better results may be achieved by taking ginkgo in combination with panax ginseng or codonopsis.

Risks and Cautions Related to Ginkgo Intake 

According to the U.S. National Center for Complementary and Integrative Health, intake of ginkgo biloba is thought to be safe for healthy adults when taken by mouth in moderate amounts. Potential side effects of ginkgo may include allergic skin reactions, dizziness, headache and stomach upset. An increased risk of bleeding is possible with ginkgo if you are older, pregnant or have a known bleeding risk. Ginkgo has been shown to interact with blood thinners (anticoagulants), so do not take it if you are currently on a blood-thinner medication. For similar reasons, you should not take ginkgo before undergoing surgery or dental procedures. Also, do not eat raw or roasted ginkgo seeds, because they can cause serious side effects and may be poisonous.

You Need B Vitamins if You Take Ginkgo Biloba 

A word of caution related to ginkgo biloba: Its seeds contain ginkgotoxin (4'-Omethylpyridoxine), an “antivitamin” that may lead to neurological problems in certain people, particularly those who are deficient in certain B vitamins. B vitamins are important not only when you consume ginkgo, but they are also useful in helping to reduce brain shrinkage and prevent degenerative brain diseases (J Epilepsy Res. 2015).

5. Soy Isoflavones

Soy isoflavones are polyphenols found in soy products and other plants. They preferentially interact with a type of estrogen receptor involved in cognitive functions. Because they interact with estrogen receptors, soy isoflavones have also been studied for preventing menopausal symptoms and premenstrual syndrome.

A large meta-analysis of 10 randomized controlled trials reported that soy isoflavone supplementation significantly improved overall cognitive function and visual memory in people under 60 years old from non-US countries (Menopause. 2015).

In a large double-blind randomized controlled trial of postmenopausal women, treatment with isoflavone-rich soy protein for several years improved visual memory, but not other cognitive functions compared to control (Ref). More benefits were seen in women between 5–10 years of menopause than those 10 years post-menopause.

In older men and women, soy isoflavones treatment resulted in improved spatial memory and construction, verbal fluency, and dexterity, but worse executive function (Ref).

In young healthy adults, high soy diet for 10 weeks resulted in significant improvements in short-term and long-term memory and in mental flexibility, but not in attention or category generation compared to those in the control diet (Ref). Women, but not men, on the high soy diet also improved in letter fluency and planning.

However, soybean oil is a different kettle of fish. We’ve often warned against the use of soybean oil.  Soybean oil is a source of an omega-6 fat called linoleic acid (LA), which is highly susceptible to oxidation and is typically from GMO seeds. Not only is soybean oil loaded with trans fat, which has been linked to heart disease, soybean oil may also cause irreversible changes in your brain.

6. Vitamin D

People with lower vitamin D levels appear to have a higher risk of age-related diseases, including cognitive decline and Alzheimer's. While a few small studies suggest that vitamin D supplementation may improve some aspects of cognitive functions, more studies are required to confirm that it can protect against dementia. Vitamin D is usually safe when used as directed.

People with low levels or low dietary intake of vitamin D appear to be more likely to develop mild cognitive impairment (MCI) or dementia [Ref], but no clinical research has yet tested whether treatment with vitamin D can protect from this risk. In a small non-randomized clinical trial, elderly people receiving vitamin D3 supplements had better cognitive function compared to untreated people, with particular improvement in executive function [Ref], but the study was not controlled or designed to look at the risk of cognitive decline.


7. Panax Ginseng

Panax ginseng is a plant used in traditional Chinese medicine (also known as Korean or Asian ginseng). Its root contains compounds called ginsenosides, which have anti-oxidative and anti-inflammatory effects. Panax ginseng is purported to enhance longevity, promote cognitive functions, and alleviate fatigue.

A meta-analysis of five double-blind randomized controlled trials in healthy subjects reported that Panax ginseng treatment for 8-12 weeks showed improvement in some aspects of cognitive function, behavior, and quality of life, though the evidence was not convincing or consistent across studies (Ref).

2020 double-blind randomized controlled trial of 52 healthy individuals reported that Panax ginseng treatment (1 g/day) for eight weeks significantly increased the volume of a brain region important for memory and improved scores on executive function, attention, and memory, effects that were not seen in the placebo group.

In one 2020 systematic review that included two randomized controlled trials for ginseng, both trials showed that ginseng supplementation resulted in significant improvements in cognitive outcomes; however, due to the limitations in the methodological quality of the trials, results have not been conclusive.

The longest placebo-controlled clinical trial included 61 Alzheimer’s patients and lasted two years (Ref). In the low-dose Panax ginseng group (4.5 g/day), cognitive scores (as measured by the Mini-Mental State Examination) improved after 48 weeks, then slightly decreased at 96 weeks. In the high-dose group (9.0 g/day), cognitive scores showed slight improvement at 48 and 96 weeks. In this study, maximum cognitive improvement was observed around 24 weeks, then sustained for two years.

8. Coffee and Caffeine

Caffeine, a natural component of coffee and tea, is the most commonly consumed psychoactive substance in the world. It has well-documented effects on mental alertness.

In a 2012 study, individuals with MCI (mild cognitive impairment) were less likely to progress to dementia if they had higher caffeine levels in their blood.

9. Magnesium 

Magnesium is an essential mineral for the body and brain, which is needed for the proper functioning of many enzymes that carry out biochemical reactions. Sufficient levels of magnesium are usually obtained through a healthy diet.

People who consume diets rich in magnesium have been reported to have a lower risk of cognitive decline in two observational studies. 

Specifically, one study followed more than 1,400 healthy older adults for 8 years and reported that higher dietary magnesium intake was associated with an 86 percent reduced risk of developing mild cognitive impairment for men but not women [Ref]. 

Another 17-year study that followed more than 1,000 Japanese adults over the age of 60 found that those who consumed more than 200 mg of magnesium per day were 37 percent less likely to develop any type of dementia and 74 percent less likely to develop vascular dementia [Ref].

One 2016 pilot randomized controlled trial of 44 patients reported that magnesium L-threonate improved overall cognitive ability for elderly patients with memory complaints (R).

10. Geen Tea (EGCG)

Green tea is prepared from dried leaves of Camellia sinensis, a perennial evergreen shrub. It contains several compounds that are possibly beneficial to brain health, including caffeine, catechins (polyphenols like EGCG), and L-theanine (an amino acid derivative).

Greater green tea consumption was associated with lower risk of dementia in two studies conducted in Japan, with the larger study reporting 27% lower risk in people who drank at least 5 cups a day [R]. Tea drinking was also associated with higher verbal fluency in elderly Chinese people (i.e., 80–115 years old) [R].

Two double-blind randomized controlled trials have evaluated the effects of green tea extract on cognitive functions. One trial in 91 patients with mild cognitive impairment reported that the combination of green tea extract and L-theanine for 16 weeks resulted in significant improvements in memory and attention, particularly in patients who had relatively severe baseline impairment [R]. 

The second trial examined the acute effects of a drink containing 27.5 g of green tea extract and reported that the drink increased brain connectivity associated with working memory and the degree of connectivity correlated with the magnitude of improvement in working memory [R].

11. Quercetin

In this study published in Neuropharmacology in 2015, researchers gave quercetin to mice with Alzheimer’s, injecting them with quercetin every two days for three months. By the end of the study, the injections had reversed several markers of Alzheimer’s, and the mice performed much better on learning tests.

In a separate study published in 2018, researchers gave mice with Alzheimer’s a quercetin-rich diet. Researchers found the diet improved brain function in mice with early-middle stage Alzheimer’s, although it had no significant effect on middle-late stage Alzheimer’s.

You may have heard that coffee is linked to a reduced risk of Alzheimer’s. There’s certainly some research to back that claim up. However, recent research has suggested that quercetin (not caffeine) is the primary compound in coffee responsible for protective effects against Alzheimer’s.

12. Molecular Hydrogen

Molecular hydrogen (H2) is a gas that is found in trace amounts in the air (0.00005%). It can act as an antioxidant and is thought to protect cells from oxidative stress-related damage. Hydrogen can be inhaled as a gas at low concentrations (1-3%) or infused into water. A saturated solution of hydrogen contains 1.6 parts per million (ppm) hydrogen. In preclinical models, molecular hydrogen was most beneficial when used chronically as a preventative measure, before the onset of pathology. Hydrogen therapy is generally considered safe.

A few clinical trials have tested whether molecular hydrogen preserves cognitive function in populations at high risk for cognitive decline, in the form of hydrogen-rich water, hydrogen-rich saline infusions, or hydrogen gas inhalation. 

In the trial of people with mild cognitive impairment, APOE4 carriers were the only subgroup to show benefits on cognitive tests in response to hydrogen-rich water consumption.

Hydrogen-infused water has been granted Generally Recognized as Safe (GRAS) status by the FDA, which means that it is generally considered safe for consumption.

Read More: A scientific review on the potential of molecular hydrogen in preventing and treating diseases.

Additional Dementia's Prevention Strategies

In addition to the supplement recommendations mentioned above, the following additional prevention strategies will help you avoid Dementia and Alzheimer's.
  1. Eat real food, ideally organic
  2. Replace refined carbohydrates with healthy fats
  3. Avoid gluten and casein
  4. Optimize your gut flora
  5. Get sufficient quality sleep
  6. Exercise regularly or at least be physically active
  7. Intermittent fasting

Alzheimer’s Disease Linked to Exposure to Aluminum

A study published in the Journal of Alzheimer’s Disease (JAD) on January 13, 2020, supports a growing body of research that links human exposure to aluminum with Alzheimer’s disease (AD). Researchers found significant amounts of aluminum content in brain tissue from donors with familial AD. The study also found a high degree of co-location with the amyloid-beta protein, which leads to early onset of the disease.

“This is the second study confirming significantly high brain accumulation in familial Alzheimer’s disease, but it is the first to demonstrate an unequivocal association between the location of aluminum and amyloid-beta in the disease. It shows that aluminum and amyloid-beta are intimately woven in the neuropathology,” explained lead investigator Christopher Exley, PhD, Birchall Center, Lennard-Jones Laboratories, Keele University, Staffordshire, UK.

According to Dr Exley:

“Either way, the new research confirms my resolve that within the normal lifespan of humans, there would not be any AD (Alzheimer's Disease) if there were no aluminum in the brain tissue. No aluminum, no AD.”

Editor's Note: Clearly, Alzheimer's is not caused by a single factor. Your diet and lifestyle play significant roles, as do other toxic exposures. To learn more about the factors that raise your risk for Alzheimer's, see "How Iron Overload Affects Your Risk of Alzheimer's Disease" and "How Vegetable Oil Wrecks Your Health".

Wrapping It Up

While studies suggest that taking certain supplements may help prevent Alzheimer's, the best way to promote longevity and overall health is to engage in healthy practices like consuming a nutritious diet, engaging in regular exercise, stop smoking and reducing stress.


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