Are mushrooms an effective early dietary intervention for Alzheimer’s Disease?

By Hugo Francisco de SouzaAug 9 2023Reviewed by Sophia Coveney

In a study published in the journal Foods, researchers reviewed available literature on the potential anti-Alzheimer's disease properties of mushrooms.

Their review highlights how bioactive compounds in mushrooms, especially neuroprotective small molecules, might help delay the onset and progression of the condition and present mushrooms as a functional food and early dietary intervention for individuals living with the disease.

Alzheimer’s disease and its association with diet and lifestyle

Alzheimer’s disease (AD) is a progressive neurodegenerative condition that destroys memory and other critical mental functions. It is the leading cause of dementia and hitherto has no cure.

AD is characterized by both brain cell connections and the cells themselves degenerating, resulting in the progressive decline of memory and cognitive functions. In extreme cases, AD can result in an almost perpetual state of confusion and cause drastic personality and behavioral changes in patients.

AD predominantly affects individuals above 65, though early-onset AD is a growing concern in patients in their mid-to-late 30s. It is estimated that one in every nine adults above the age of 65 suffers from some degree of AD.

Pathologically, AD is predominantly identified and characterized by excess deposition of extracellular beta-amyloid (Aβ) plaques and tau tangles (Tau). While research into the pathology of AD is ongoing, the mechanisms behind AD progression remain elusive, with no cure currently available for the condition. AD is a multifactorial condition, with studies identifying genetic, environmental, dietary, age, and sociodemographic contributors to AD prevalence and progression.

Thus, while prevention of AD onset and delay in disease progression is the focus of most research into potential therapeutic interventions, a growing body of evidence points to dietary and lifestyle choices playing a role in disease manifestation and in individuals who already have the condition, disease management.  

Health behaviors and nutritional changes are strong predictors of AD prevalence in adults, with studies on the Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets all showing statistically significant correlations with improved memory retention and cognition in the elderly.

Positive health behaviors, including prolonged intermittent fasting and consumption of fresh, selenium-rich foods, have been independently shown to delay or even reverse the symptoms of AD, potentially via calorific restrictions and antioxidant and anti-inflammatory mechanisms, respectively. Research has also identified tea, the most popular beverage across the globe, to delay AD progression effectively when consumed in moderation,.

“Whole plant foods, such as mushrooms, berries, garlic, and turmeric, were found to effectively prevent and improve cognitive deficit via regulating the main pathway of neuroinflammation, lipoxin A4 (LXA4)-nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinases (MAPK). These beneficial effects were mainly attributed to their high contents of functional macromolecules, including polysaccharides, bioactive peptides, and polyphenols; therefore, whole-plant foods can be part of a dietary plan to prevent the progression of AD.”

Li et al. (2023)

Poor health behaviors have been shown to have the opposite cognitive effect, with studies linking high alcohol consumption with an increased risk of dementia in a 3,933,382 individual-strong Korean cohort.

The degree of food processing has also been linked to cognitive loss, with a 10-year-long study finding a positive correlation between ultra-processed (“high sugar, high fat, and high energy density”) food consumption and an increased risk of dementia.

Research into the Western diet (foods rich in simple sugars and saturated fatty acids) has identified it as one of the leading risk factors associated with AD due to memory impairment caused by damage to the blood-brain barrier (BBB).

Thus, the importance of healthy food consumption, especially foods rich in bioactive compounds known to promote cognition, cannot be understated. This review is a synthesis of available literature on the benefits of mushroom consumption on AD, with notes on the biochemical properties that make it an ideal early dietary intervention in the condition.

The magic of mushrooms

Mushrooms are the fleshy, spore-bearing fruiting body of macrofungi, typically produced above ground on soil or their food source.

The nutritional and medicinal properties of mushrooms have been appreciated for centuries, which, when clubbed with their unique taste and umami flavor, have been a staple in human diets globally.

Recent in vitro and in vivo studies have identified anticancer, antioxidant, antimicrobial, and neuro-protective properties in mushroom biomolecules, implying that mushroom consumption shows potential in delaying or even preventing cognitive impairment (CI) associated with AD.

Cohort studies on Japanese and Singaporean individuals above 65 have elucidated that frequent mushroom consumption significantly decreases dementia risk. The Singaporean cohort study revealed that as little as 300 g of mushrooms per week (two or three mushrooms) was sufficient to reduce mild cognitive impairment (MCI) risk by 50%.

Studies on Hericium erinaceus (lion’s mane mushroom) have shown that its extracts and biomolecules effectively reversed cognitive and behavioral deficits in both preclinical animal trials and, remarkably, in clinical human trials.

The present review examined the neuroprotective effects of mushroom components on AD, especially polysaccharides, terpenoids, proteins, lipids, and phenolic compounds.

One of the medical interventions involves using compounds that inhibit the function of acetylcholine (a neurotransmitter) in the brain by blocking the acetylcholinesterase (AChE) receptor.

Polysaccharide extracts from Coprinus comatus (shaggy mane mushroom) and Coprinellus truncorum were rich in β-glucans which exerted AChE inhibitory activity without the typical side effects associated with synthesis medicines.

Similar in vitro studies on murine models using polysaccharide extracts from Grifola frondosa (Maitake mushrooms), Pleurotus eryngii (king trumpet mushroom), and H. erinaceus all described neuroprotective and antioxidant properties in aging rats. The rats showed significantly improved cognition implying a reversal of neurodegeneration.

Inflammation, supported by glial cell activity, is one of the best-studied factors associated with AD and dementia. Mushrooms have a surprisingly high protein content, much higher than most food crops and vegetables. These proteins are comprised of novel peptides, some of which have been shown to possess potent anti-inflammatory properties.

“Novel selenium peptides obtained from selenium-enriched Cordyceps militaris showed protective effect in H2O2-injured PC12 and alleviated the cognitive impairment in lipopolysaccharide (LPS) injured mice through its antioxidative, anti-inflammatory, and regulating properties on gut microflora.”

Li et al. (2023)

While the lipid content of mushrooms is relatively low (0.1 – 16.3%), the oleic and linolenic acids that mushrooms contain have been shown to have similar anti-inflammatory effects as their peptides. Alpha linoleic acid was observed to protect murine neurons from Aβ-induced glial-cell-mediated neuroinflammation effectively. Mice in the test cohort (consuming the alpha-linoleic acid) showed significantly reduced neuronal cell loss compared to controls in an Aβ-infused mouse model.

Melatonin, ergosterol, terpenoids, and phenolic compounds extracted from mushrooms have been found to exhibit a whole spectrum of anti-AD benefits, ranging from neuro-protective to anti-inflammatory properties, especially in terms of neurons in the brain. Evidence points to brain inflammation as the primary cause of neurodegenerative disorders, including AD.

Consumption of these mushrooms or their extracts might pave the way for future therapies and interventions which replace conventional synthetic compounds with naturally derived, cheap, and nutritious alternatives, aiding in the campaign against AD and other age-related cognitive conditions.

“One meat, one vegetable, and one mushroom” – FAO

The Food and Agriculture Organization of the United Nations (FAO) has prescribed the above as the ideal human dietary structure.

Health behavior and dietary outreach campaigns, along with research into novel biopharmaceutical properties of foods and lifestyles, are beginning to reveal diets (e.g., MIND), lifestyle choices (intermittent fasting and reduced alcohol consumption), and nutrition (mushrooms) with side-effect-free potential to delay or even reverse the effects of terminal human ailments like AD and cancer.

In the present review, researchers documented literature supporting mushroom consumption as a means to treat or delay AD, along with up-to-date research on the biomolecule pathways that make these humble fungi such treasure troves of good health and cognition.

“We envision increased clinical data supporting the efficacy of food therapy in AD prevention. Furthermore, we eagerly await the discovery and clinical application of novel bioactive compounds derived from mushrooms, offering promising prospects for enhancing AD prevention and treatment, and ultimately improving public health.”

Li et al. (2023)