Alzheimer’s disease (aka Alzheimer’s dementia or “AD”) is a progressive neurodegenerative condition that causes the brain to atrophy and the neurons to die over time. The result is increasingly impaired memory and a progressive loss of cognitive and physical function. As the disease advances, symptoms include problems with language, disorientation, mood swings, loss of motivation and self-neglect. Ultimately, people suffering from AD tend to gradually withdraw and disconnect from their surroundings ultimately leading to death.
The advance of AD is associated with the buildup of amyloid plaques and neurofibrillary tangles in the brain as well as the loss of neuronal connections. While the causes of AD are not yet fully understood, there are a number of factors that have been associated with the development of the disease. These include genetic risk factors (40-65% of people diagnosed with Alzheimer's have the APOE-e4 gene), the effect of environmental toxins, a history of head injuries, depression, high blood pressure, as well as socio-economic circumstances.
According to the Alzheimer’s Association, 1 in 3 older adults dies of AD or some other kind of dementia . and over the last two decades Alzheimer’s deaths have increased by 145%. As our life expectancy increases, so does the likelihood of being afflicted by this disease. Currently, AD is considered incurable and, frustratingly, over the last few decades very little progress has been made in the development of effective therapeutics, despite significant investment Consequently, the treatment options for AD are heavily dependent on palliative care. That’s why any complete longevity protocol needs to focus on prevention.
We already know that any strategy to protect ourselves against the risk of long-term cognitive decline starts with a healthy diet, exercise, and high-quality sleep. If you’ve already covered these basic pillars, the next obvious question is what else can you proactively do to attempt to ward off Alzheimer’s and other neurodegenerative conditions?
One interesting possibility is designing a supplementation strategy that can enhance your nutritional status and provide your brain with substrates that can help it stay healthy. Our research on this topic led us to identify 12 natural supplements that have been reasonably shown to support optimal brain health and function. Let’s dive in.
Magnesium made the top of our list because of its involvement in over 300 enzymatic reactions in our metabolism and its role in the activation of over 1,300 metabolic pathways. Magnesium is found in significant quantities in green leafy vegetables, nuts, seeds, fortified foods, and some dairy products. However, despite its availability in food, the average American doesn’t get enough magnesium in their diet.
Magnesium deficits can have major adverse consequences on brain health because of the critical roles it plays inside the cell in connection with stabilizing nucleic acid and protein structure, reducing errors in DNA replication, supporting mitochondrial health and function, and reducing reactive oxygen species. Studies have also shown that low concentrations of magnesium contribute to Alzheimer’s pathology. According to this review of studies on animal models, persistently low levels of magnesium in the hippocampus (the memory center) is correlated with impaired learning, impaired emotional memory, and impaired ability to recover cognitive function following a brain injury. Conversely, this study showed that when levels of magnesium were increased in rat brains, short-term synaptic facilitation and long-term potentiation improved. This translates to enhancements in learning and memory. In humans, this study suggests that Alzheimer’s patients who are supplemented with magnesium showed improvements in memory.
Go deeper into the type of magnesium supplement that may be right for you.
Melatonin is produced by the pineal gland and helps regulate our sleep/wake cycle. Levels of circulating melatonin decrease in the morning and increase as the day progresses to get us ready for sleep. As we age, the pineal gland undergoes changes (e.g., calcification, reduction in size) that affect its structure and function. The result is a decrease in melatonin production and the gradual loss of a healthy circadian rhythm. Scientists have observed that Alzheimer’s patients show a significant reduction in melatonin levels, which contributes to the poor-quality sleep symptoms associated with the disease.
Luckily, there is evidence that suggests that the drop in naturally occuring melatonin as we age can be addressed through supplementation. This study examining the two-way relationship between disrupted circadian rhythms and development of Alzheimer’s showed that supplementing melatonin helps regulate the sleep cycle and reduce sleep-related symptoms in Alzheimer’s patients. Melatonin supplementation also helps reduce the incidence of sundowning, or “late-day confusion” that afflicts many patients.
We also came across some research that shows how melatonin may improve cognitive impairment in Alzheimer’s patients by increasing removal of toxic proteins by the brain glymphatic system.
The two-way relationship between circadian rhythm disruption and AD.
Dive deeper into the connection between sleep and circadian rhythm disruption, stress and Alzheimer’s disease with this study.
Docosahexaenoic acid (DHA) is considered one of two non-essential fatty acids. Our bodies have the ability to synthesize it, but competition for desaturation enzymes between its precursor (ALA) and other fatty acids makes the rate of conversion extremely low. As such, DHA must be supplemented through the diet. DHA is the most abundant fatty acid found in the brain (40%) and promotes brain-derived neurotrophic factor (BDNF) which stimulates nerve growth.
Results from the research we found on DHA supplementation are mixed. Some animal studies have shown that rats supplemented with DHA show a reduction in amyloid plaque accumulation in the brain, the signature symptom of Alzheimer’s. For example, this study performed in mice carrying the mutant genes associated with Alzheimer’s pathology showed that supplementation with DHA reduced the accumulation of both amyloid β and tau proteins in the brain.
Epidemiological studies have also suggested positive effects of DHA supplementation in humans. This paper published using data from the Framingham Heart Study, suggests that high plasma concentration of omega-3’s, particularly DHA, reduced the risk of all-cause dementia by 47%. As often is the case, however, not all experiments show the same results. For instance this randomized study (N=295) showed that DHA supplementation did not significantly slow the rate of cognitive and functional decline in patients with moderate AD.
Despite the mixed research data, we are still inclined to think that DHA supplementation can be an important ingredient in any longevity protocol, particularly when we consider that most of us do not get sufficient DHA from our diets and the proven safety of this supplement.
Get Started: Click here to purchase our staff pick—Vegan Omega-3 EPA + DHA Softgels by Amala Vegan ($24)
B6, B12, and Folate
Vitamins B6 and B12 are part of the B-complex, a group of water-soluble vitamins that are essential for normal body function. Specifically, B6 (pyridoxine) is a coenzyme that serves functions in amino acid, glucose, and lipid metabolism, hemoglobin synthesis, and gene expression.
B12 (cobalamin) is a coenzyme that serves functions in amino acid and lipid metabolism, DNA synthesis, myelin synthesis in the nervous system, and maturation of red blood cells. Research on the efficacy of B6 and B12 on Alzheimer’s disease is mixed. The results of these meta-analyses (study 1, study 2) suggest that there is no significant improvement in cognitive function following supplementation with B vitamins. Conversely, the three published studies from the VitaCog trial (N=266) (study 1, study 2, study 3) all suggest that B vitamin supplementation protects against cognitive decline in those with mild cognitive impairment and high homocysteine levels.
Given these mixed study results (we are not getting into the potential limitations of each study’s design) we can’t necessarily conclude that B vitamins have a direct effect on cognitive decline. However, there seems to be sufficiently solid evidence that supports the role played by B vitamins in mediating homocysteine levels. This is relevant in that moderately elevated plasma homocysteine has been shown to be a strong, but modifiable, risk factor for vascular dementia and Alzheimer's disease.
Folate (aka folic acid or vitamin B9) is an essential nutrient and coenzyme required for amino acid metabolism and DNA/RNA synthesis. Like B6 and B12, folate has not been definitively shown to significantly affect cognitive function in clinical trials. Nevertheless, a good number of observational studies (study 1, study 2, study 3, study 4, study 5) have demonstrated that low levels of folate are correlated with higher levels of cognitive impairment and an increased risk for Alzheimer’s. The mechanism by which folate may play a role in slowing cognitive decline is thought to be the same as that of B6 and B12, as low levels of folate in the brain correlate to high levels of homocysteine.
Interestingly, it has been found that the role of B vitamins in regulating homocysteine levels and thereby impacting cognitive function is enhanced by the presence of Omega-3 fatty acids, specifically DHA.
Get Started: Check out Matter by Elysium. It combines Omega-3s (DHA) with a B vitamin complex and antioxidants to promote brain health.
Vitamin D is a fat-soluble vitamin that has many functions in the body including calcium absorption, bone health, cell growth, neuromuscular and immune function, and glucose metabolism. When it comes to the potential role of vitamin D in preventing cognitive decline, we came across this observational study that showed an association between vitamin D deficiency and a substantially increased risk of all-cause dementia and Alzheimer disease. Based on data collected from 1,658 elderly adults over a period of 6 years, the study’s authors found that moderate vitamin D deficiency correlated with a 53% increase risk of all-cause dementia and severe vitamin D deficiency correlated with a 125% increased risk of all-cause dementia when compared to individuals with normal vitamin D levels.
Clinical trials are needed to confirm the results of this observational study. Of course, we also found studies that showed no effect of vitamin D on cognitive decline. Nevertheless, there is no debate as to the fact that vitamin D is an essential nutrient and that it’s deficiency can result in serious health complications, including normal brain function. Furthermore, it has been documented that a significant percentage of US adults have vitamin D deficiencies and they may not even know it.
Many healthcare practitioners suggest we get our vitamin D from exposure to direct sunlight. The caveat is that in order to get vitamin from the sun, you need to have most of your skin exposed without sunscreen for anywhere between 10-60 minutes depending on your skin color. Since the majority of people tend to spend most of their time indoors and many try to avoid direct sunlight exposure to prevent skin cancers, this may not be sufficient. To complement this source, we can consume foods fortified with vitamin D, or choose to supplement.
Get started: find out if you have a vitamin D deficiency (or if you are lacking any other essential nutrients) by testing. Baze offers a comprehensive nutritional test from the comfort of your home.
Coffee is one of the most widely consumed stimulants in the world and has been shown to have many positive health effects when taken in moderation. When it comes to the brain, research in animal models has shown that coffee and caffeine have significant neuroprotective effects. Imn the context of AD, coffee and caffeine appear to act through multiple mechanisms that suppress the production and accumulation of amyloid plaques and tau protein build up.
Data in humans seems to suggest something similar. This longitudinal study (N=6467) examined self-reported caffeine consumption over a period of 10 years. At follow-up, participants who consumed more than 261 mg of caffeine per day were 26% less likely to develop incident dementia or any cognitive impairment when compared to those consuming less than 64 mg of caffeine per day. Additional longitudinal studies examining caffeinated coffee/tea and the risk of dementia, Alzheimer’s, or impaired cognitive functioning also suggests that coffee is neuroprotective.
Learn More: Click here to read an additional study on the effect of coffee on amyloid plaque formation in the brain.
Coffee Fruit Extract
Coffee fruits (aka coffee berries) are round stone fruits produced by the coffee plant. Coffee beans grow inside of coffee fruits and while the beans are harvested and ground up to make coffee, the extract of the leftover fruit is used in supplements. So far, only one small scale trial has tested the effect of coffee fruit extract on brain health. This randomized trial of 25 healthy adults showed that supplementation of coffee fruit extract increased BDNF (Brain-Derived Neurotrophic Factor) by 143% when compared to controls. This is relevant because reduced levels of BDNF have been observed not only under normal aging conditions but are more pronounced in the presence of pathological conditions such as AD and Parkinson’s.
While the benefits of Coffee Fruit Extract require additional research through larger scale trials, these initial findings make this an interesting supplement to experiment with.
Learn more: read the Alzeheimer’s Drug Discovery Foundation’s assessment of the potential of Coffee Fruit Extract.
Turmeric is a flowering plant and member of the ginger family. Most of us know it for its use in curry where it adds both flavor and that characteristic yellow color. Turmeric is known and widely used in alternative medicine for its anti-inflammatory properties, though more recently it has garnered attention as a possible way to prevent Alzheimer’s. Curcumin, a component of turmeric, is especially interesting to scientists. This 2018 review suggests that curcumin can help prevent the destruction of neurons that occurs in Alzheimer's disease and may inhibit plaque formation in the brain due to its high binding affinity to amyloid. Anecdotal observation also suggests a link between turmeric and human health, primarily citing the low incidence of Alzheimer’s disease in India. Most recently, this randomized trial (N=40) showed that supplementation of 90 mg of curcumin twice daily for 18 months improved memory and attention in non-demented adults and decreased amyloid and tau protein accumulation in brain regions associated with memory and mood. Curcumin is also thought to aid improvement in cognitive function of AD patients due to its anti-inflammatory and antioxidant properties as its ability to chelate iron and other toxic metals.
Go Deeper: with this comprehensive overview on the effect of curcumin on Alzheimer's disease
Medium chain triglycerides (MTCs) oils have become popular of late as a supplement in support of Ketogenic diets. MCTs are dietary fats that consist of a carboxyl chemical group attached to a carbon chain that is 6-12 atoms long. MCTs are passively diffused through the GI tract, do not require bile salts for digestion, and do not need additional modification before the body can use them for energy. For this reason, MCT oils are often administered as part of tube feeds for malnourished patients or to people who cannot metabolize lipids. This also makes MCTs a good alternative energy source for the body and, especially the brain.
Specifically, reduced glucose metabolism is often seen in brain scans of patients with Alzheimer disease and other dementias. This implies that patients suffering from AD may not be able to provide their brain with the energy it needs to function properly. MCTs can cross the blood-brain barrier and provide an alternative source of energy. This in turn may aid in improving cognitive function.
Our research surfaced two studies that suggest this might be true. The first study (N=152) examined the effects of an oral ketogenic compound, AC-1202 (a MCT), on adults with mild to moderate Alzheimer’s. After 90 days, study authors found that supplementation with AC-1202 improved scores on cognitive tests when compared to placebo. The second study (N=20) examined the effects of emulsified MCTs on adults with Alzheimer's or mild cognitive impairment. After 120 minutes, study authors found that treatment participants had better recall on cognitive tests when compared to controls.
Get Started: MCT oils can be hard on your digestive system, so we recommend HVMN’s line of MCT oil powders. Check them out here.
As the connection between our gut microbiome and brain health has grown clearer, probiotics have also come into focus as a possible preventative measure for age-related cognitive decline and Alzheimer’s disease. For example, we found this NIH-funded study that examined the microbiomes of AD sufferers through genetic sequencing and compared them to those of healthy individuals. They found that the microbiome of the former group was much less diverse and showed a lower density of healthy bacteria such Bifidobacterium. They also found increased density of some harmful types of Bacteroidetes. The study suggests that unique composition of the microbiome of AD patients could be contributing to the progression of their disease.
Additional research summarized in this peer-reviewed book chapter suggests that probiotics can prevent and perhaps even act as a treatment for AD. Animal models have shown that cognition and memory storage decline with age, but are particularly disrupted in the Alzheimer’s brain. Treatment of mice with probiotics like Lactobacillus and the aforementioned Bifidobacterium seemed to mitigate the damage of AD and slow cognitive decline.
In humans, there has only been one clinical trial of probiotics in Alzheimer’s patients. Sixty patients were split into equal groups. The treatment group received 200mL/day of enriched probiotic milk; controls received a placebo. After 90 days, when compared with controls, the probiotic treated patients had increased their scores on cognitive tests an average of 28%. This group also showed lower levels of the inflammatory marker C-reactive protein, as well as improved insulin resistance.
Get Started: Read the Cleveland Clinic’s guide to selecting the right probiotic for you.
Prebiotics are fiber-rich foods like fruits, vegetables, whole grains, nuts, seeds and resistant starches, that not only help regulate our digestive systems but provide sustenance for our gut microbes. Research specifically addressing prebiotics in Alzheimer’s disease is just picking up, but we found some studies that address how high-fiber foods intersect with lower cognitive decline in animal models.
For example, this study showed that aging mice fed a high-fiber diet had higher levels of butyrate, a short chain fatty acid (SCFA) that is produced primarily through bacterial fermentation in the gut. Higher levels of butyrate were in turn linked to lower inflammation markers as well as lower amyloid accumulation in the brain, when compared to mice fed a low fiber diet.
We know that diets rich in fiber help keep the gut healthy by feeding our “good” bacteria. This other in vitro study also seems to corroborate that the higher levels of butyrate and other SCFAs resulting from fiber-rich diets, can prevent beta amyloid aggregates from accumulating in the brain.
Get Started: Check out this list of the 15 best prebiotic foods from Eat This, Not That.
While we always advocate trying to get all your essential nutrients through diet, the reality is that the nutrient density of even high-quality vegetables, fruits and grains has been increasingly reduced by the erosion of our topsoil. Furthermore, for some of the nutrients we’ve discussed, it is hard to consume “therapeutic” levels of them through diet alone. That’s why we are always open to supplementing when it makes sense. As with any decision concerning your longevity protocol, the best strategy is to consult an expert health practitioner that can help guide you through the choices that are ideally suited for you.
Have you tried any of these natural supplements to support your brain health? Share your experiences with us: firstname.lastname@example.org
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