Neurodegenerative Disease: Improving Outcomes Through Nutrition

According to the National Institute of Environmental Health Sciences, neurodegenerative disorders affect over 7.2 million Americans,¹ and likely many more if those with mild cognitive impairment are included. These disorders are debilitating conditions that impact neuron function and increasingly affect function throughout the disease course. While age is a major factor in the risk of onset, genetics and environmental factors also play a part.¹ Adopting a nutritional approach for ameliorating symptoms of these disorders has already proven beneficial for some patients, and personalized nutrition strategies have been suggested as preventative tools.

The most common neurodegenerative disorders are Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Neuroinflammation, oxidative stress, and mitochondrial dysfunction have all been noted in the progression of these diseases.^2,3 While there is no cure for these disease states, clinical treatments for AD, PD, and MS symptoms may include medications, lifestyle modifications, and some other types of therapies.^4-6 Lifestyle therapies may include specific foods, natural supplements, and diet plans. For example, with PD, each patient’s treatment is personalized based on their symptoms and disease progression and may include nutrient support from:

• Antioxidants⁵ 
• Polyphenols⁷
• Resveratrol⁸
• A Mediterranean-style diet^5,7

] (Video Time: 3 minutes) Monique Class, MS, APRN, BC[MC1] , is a board certified family nurse practitioner and clinical nurse specialist in holistic health at The Center for Functional Medicine in Stamford, CT. She is a senior faculty member for The Institute for Functional Medicine, currently serves as a clinical instructor for the Yale Graduate School of Nursing, and is a founding member and director of coaching development for the Functional Medicine Coaching Academy.

From Foods to Nutrients to Dietary Patterns: Prevention and Treatment

Specific nutrients and dietary patterns have been investigated for their neuroprotective properties. Increased diet quality and adherence to dietary guidelines that emphasize consumption of fruits, vegetables, fish, and fiber were related to better cognition among those with and without cognitive impairments in two recent cross-sectional studies.^9,10 In addition, specific nutrients such as omega-3 fatty acids and vitamin D, and specific diets such as the Mediterranean and ketogenic diets, have surfaced in recent neurodegenerative disease research with suggested benefits of prevention, slowing progression of disease symptomology, and improving quality of life for patients.^11-17

WALNUTS

Walnuts are a rich source of omega-3 fatty acids and antioxidants and have been studied for their potential anti-inflammatory brain health benefits. A 2020 review noted that results from a combination of animal and human studies suggest that adding walnuts to a patient’s diet may improve cognition and reduce risk of neurodegenerative diseases such as AD and PD.¹⁸

In one example, a 2015 randomized clinical trial with 447 cognitively healthy participants supplemented the anti-inflammatory Mediterranean diet with either extra virgin olive oil (1 L/wk) or mixed nuts (30 g/d, which included 15 g of walnuts).¹⁹ While results indicated that both supplemented diets improved overall cognitive performance, only the nut-supplemented diet reported significant improvement for memory testing compared to the control group.¹⁹ Expanding on this clinical trial, a 2022 randomized controlled trial (RCT) (n=224 abdominally obese participants or those with dyslipidemia) investigated the effects of Mediterranean diets supplemented with higher levels of polyphenols, including 28g of walnuts per day, on age-related brain atrophy.²⁰ After the 18-month intervention, results indicated that greater polyphenol intake (in the form of Mankai, an aquatic plant rich in polyphenolic compounds as well as green tea and walnuts) and less red and processed meat intake were significantly and independently associated with reduced brain atrophy (as measured by hippocampal occupancy score) compared to controls.²⁰

RESVERATROL

Resveratrol is a polyphenol that is found in many foods, including blueberries, dark chocolate, and grapes, and it is known to have many benefits, including antioxidant, anti-inflammatory, and neuroprotective effects. Animal and in-vitro studies have suggested that resveratrol has the potential to improve several disease states, including neurodegenerative disorders.²¹ Human clinical trial results have also been promising.

Specific to AD, two 2022 systematic reviews investigated the effects of resveratrol supplementation on the functional and cognitive performance of patients with AD. The findings indicated that resveratrol delayed cognitive impairment in patients with AD²² and improved both brain volume and AD scores for patients.²³ In other populations, a 2017 RCT with 80 post-menopausal women (aged 45-85 years) reported that after the treatment group received 75 mg of resveratrol twice daily for 14 weeks, they showed significant improvement in verbal memory and overall cognitive performance.²⁴ 

GINGKO BILOBA

Gingko biloba leaf extract has been suggested to improve cognitive function and benefit AD patients; however, clinical trials have been inconsistent, and research continues.^25,26 A 2020 review analyzed the results of randomized clinical trials and found that among those with negative results, participants tended to be healthy, young adults, dosages were mostly 120 mg or less, and the treatment durations were mostly less than 12 weeks.²⁵ For the positive clinical trials, participants tended to be elderly outpatients, dosages were typically 240 mg or more, and the treatment durations were mostly over 22 weeks.²⁵ From these details, the review suggested that while there is still controversy, Gingko biloba leaf extract may improve cognitive function in patients with mild dementia with appropriate dosage and long-term administration.²⁵

CAROTENOIDS, VITAMIN D, AND OMEGA-3

With regard to AD, the most common form of dementia, many nutrients that act as antioxidants and anti-inflammatory agents may influence the mechanisms associated with the disease pathology. These include:¹⁵

• Phenolic compounds (found in olive oil, turmeric, berries, etc.)
• Omega-3 fatty acids (found in fish, walnuts, etc.)
• Fat-soluble vitamins (vitamins A, D, E, K)
• Isothiocyanates (found in cruciferous vegetables)
• Carotenoids (the orange, yellow, and red plant pigments) 

The suggested neuroprotective properties of these nutrients are largely supported by epidemiological studies; however, there is also support from human trials. Of note, a 2018 double-blind RCT suggested that daily supplementation of carotenoids (lutein, zeaxanthin, and meso-zeaxanthin) enhanced memory in healthy adults.²⁷ In addition, a 2022 double-blind RCT (n=77 patients with mild to moderate AD) found that compared to placebo, a 12-month intervention of daily supplemental carotenoids (10  mg lutein, 10  mg meso-zeaxanthin, and 2 mg of zeaxanthin) plus 1 g of fish oil (500 mg DHA and 150 mg EPA) plus 15 mg of vitamin E improved measures of AD severity such as behavior, memory, and mood.²⁸

Regarding vitamin D status and brain health, results from a 2019 meta-analysis indicated that vitamin D deficiency may be a risk factor for dementia or AD.¹³ This meta-analysis included six AD studies with a total of 14,618 participants and 11 dementia studies with a total of 21,784 participants.¹³ A 2020 cohort study added to the evidence for this connection, suggesting that vitamin D status plus population and sociological variables impact cognition.²⁹

Multiple Sclerosis

In addition to other factors such as age, low serum levels of vitamin D may also increase risk of MS development. As a treatment for MS patients, a 2020 review highlighted the potential benefits of vitamin D therapy, including a possible reduction in disease activity and severity.³⁰ The review also reported some potential hazards from chronic, high-dose vitamin D therapy after the resolution of initial deficiency.³⁰ Omega-3 fatty acids and fish oil have also been investigated for slowing the progression of MS in adults, and a 2019 review of human studies concluded that these supplementations may reduce relapse rates and inflammatory markers and improve the overall quality of life for MS patients.¹⁶

MEDITERRANEAN, DASH, AND KETOGENIC DIETS

Promising health results have been found with interventions focused on lifestyle diets such as the Mediterranean, ketogenic, and modified Paleolithic diets. IFM educator Terry Wahls, MD, has led research into nutrition and lifestyle interventions for patients with MS. In one study, nutrition interventions improved self-reported mood and cognition in MS patients.³¹ Interestingly, the dietary component seemed to have a greater impact on these outcomes than the physical and mental health components of the program.³¹

The MIND diet, which is the Mediterranean diet in combination with the Dietary Approaches to Stop Hypertension (DASH) diet, is suggested to reduce risk of neurodegenerative diseases.^15,32 In addition, specific foods and nutrients emphasized in the Mediterranean diet, such as olive oil, nuts, omega 3s, and carotenoids, have shown promise in improving AD patient outcomes.^11,27 A ketogenic diet has also shown potential in animal and human studies for reducing symptoms for AD and PD patients due its neuroprotective properties.^17,33 Since ketogenic diets are restrictive in nature, application of this diet strategy to the elderly population or patients with neurodegenerative disorders should be done with caution regarding sufficient nutrient intake and maintaining a healthy appetite.

Treatment Considerations & Practical Applications        

Nutritional programs can have a dramatic effect on the prevention and treatment of neurodegenerative diseases. From reducing inflammatory markers and severity of symptoms to improving outcomes and quality of life, nutrition is an essential part of a patient’s personalized clinical intervention for neurodegenerative diseases. A functional medicine strategy for prevention and treatment of neurodegeneration may include the following elements:

• Therapeutic food plans such as IFM’s Mitochondrial Food Plan, which focuses on mitochondrial biogenesis.
• Nutritional support through dietary patterns and nutraceuticals that enhance specific antioxidant and anti-inflammatory agents.
• Patient-practitioner collaboration to help sustain lifestyle modifications.

Learn more about supporting patients with cognitive and neurodegenerative conditions at IFM’s Bioenergetics Advanced Practice Module.