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Neurodegenerative Disease: Improving Outcomes Through Nutrition

Making a salad

According to the National Institute of Environmental Health Sciences, neurodegenerative disorders affect well over 5.5 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, 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:5

  • Antioxidants
  • Coenzyme Q10 (CoQ10)
  • B vitamins
  • Vitamin D
  • An anti-inflammatory diet
IFM educator Deanna Minich, PhD, IFMCP, discusses the clinical application of IFM’s Mitochondrial Food Plan to support mitochondrial function and promote cognitive health.

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.7,8 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 disease progression, and improving quality of life for patients.9-16

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.17

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).18 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.18

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.19 Human clinical trial results have also been promising.

For example, a 2018 double-blind randomized controlled trial with 60 elderly participants without a noted neurodegenerative disease did not show significant improvements in verbal memory after six months of 200 mg of resveratrol per day; however, a non-significant trend in the study suggested positive effects on pattern recognition memory for those taking the resveratrol supplement.20 Also of note, a 2017 randomized placebo-controlled trial 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.21

GINGKO BILOBA
Gingko biloba leaf extract has been suggested to improve cognitive function and benefit AD patients; however, clinical trials have been inconsistent.22 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.22 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.22 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.22

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:14

  • 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, randomized, placebo-controlled clinical trial suggested that daily supplementation of carotenoids (lutein, zeaxanthin, and meso-zeaxanthin) enhanced memory in healthy adults.23 In addition, a small 2018 clinical trial of 12 participants suggested a daily combination of supplemental carotenoids plus fish oil (10 mg lutein, 10 mg meso-zeaxanthin, and 2 mg of zeaxanthin plus 1 g of fish oil—430 mg DHA and 90 mg EPA) may help slow progression in AD patients and improve quality of life.9

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.12 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.12 A 2020 cohort study added to the evidence for this connection, suggesting that vitamin D status plus population and sociological variables impact cognition.24

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.25 The review also reported some potential hazards from chronic, high-dose vitamin D therapy after the resolution of initial deficiency.25 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.15 Combining the two therapies, a 2018 randomized controlled clinical trial with 53 participants tested a daily dose of omega-3 fatty acids (two capsules containing 500 mg DHA and 106 mg EPA) and vitamin D3 supplementations (50,000 IU cholecalciferol biweekly) and measured impact on MS symptoms.26 After 12 weeks, the treatment group reported significant improvement in disability status scores and metabolic status compared with the placebo group.26

MEDITERRANEAN DIET, DASH, AND KETOGENIC DIETS
Promising results have been found with interventions focused on lifestyle diets such as the Mediterranean,27 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.28 Interestingly, the dietary component seemed to have a greater impact on these outcomes than the physical and mental health components of the program.28

The MIND diet, which is the Mediterranean diet in combination with the Dietary Approaches to Stop Hypertension (DASH) diet, is suggested to prevent neurodegeneration.13,14 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.9,23 A ketogenic diet has also shown potential in animal and human studies for reducing symptoms for AD and PD patients due its neuroprotective properties.16,29 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.16

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 issues at IFM’s Bioenergetics Advanced Practice Module.

Learn More About Mitochondrial Function
For further detail specific to brain health and nutritional support, please read the following IFM-authored articles.

Strategies for Brain Health in Midlife

Ketogenic Diet in Neurodegenerative Diseases

Nutrition: A Key Modulator of Cognitive Health

References

  1. National Institute of Environmental Health Sciences. Neurodegenerative diseases. Reviewed September 10, 2019. Accessed May 18, 2020. https://www.niehs.nih.gov/research/supported/health/neurodegenerative/index.cfm
  2. Swerdlow RH. Mitochondria and mitochondrial cascades in Alzheimer’s disease. J Alzheimers Dis.2018;62(3):1403-1416. doi:10.3233/JAD-170585
  3. García S, Martín Giménez VM, Mocayar Marón FJ, Reiter RJ, Manucha W. Melatonin and cannabinoids: mitochondrial-targeted molecules that may reduce inflammaging in neurodegenerative diseases. Histol Histopathol. 2020:18212. doi:10.14670/HH-18-212
  4. Alzheimer’s Association. Alternative treatments. Accessed May 18, 2020. https://www.alz.org/alzheimers-dementia/treatments/alternative-treatments
  5. Parkinson’s Foundation. Over the counter and complementary therapies. Accessed May 18, 2020. https://www.parkinson.org/Understanding-Parkinsons/Treatment/Over-the-Counter-and-Complementary-Therapies
  6. National Multiple Sclerosis Society. Complementary and alternative medicines. Accessed May 18, 2020. https://www.nationalmssociety.org/Treating-MS/Complementary-Alternative-Medicines
  7. Wesselman LMP, Doorduijn AS, de Leeuw FA, et al. Dietary patterns are related to clinical characteristics in memory clinic patients with subjective cognitive decline: the SCIENCe project. Nutrients. 2019;11(5):1057.doi:10.3390/nu11051057
  8. Fieldhouse JLP, Doorduijn AS, de Leeuw FA, et al. A suboptimal diet is associated with poorer cognition: the NUDAD project. Nutrients. 2020;12(3):703. doi:10.3390/nu12030703
  9. Nolan JM, Mulcahy R, Power R, Moran R, Howard AN. Nutritional intervention to prevent Alzheimer’s disease: potential benefits of xanthophyll carotenoids and omega-3 fatty acids combined. J Alzheimers Dis. 2018;64(2):367-378. doi:10.3233/JAD-180160
  10. Calil SRB, Brucki SMD, Nitrini R, Yassuda MS. Adherence to the Mediterranean and MIND diets is associated with better cognition in healthy seniors but not in MCI or AD. Clin Nutr ESPEN. 2018;28:201-207. doi:10.1016/j.clnesp.2018.08.001
  11. Power R, Prado-Cabrero A, Mulcahy R, Howard A, Nolan JM. The role of nutrition for the aging population: implications for cognition and Alzheimer’s disease. Annu Rev Food Sci Technol. 2019;10:619-639.doi:1146/annurev-food-030216-030125
  12. Chai B, Gao F, Wu R, et al. Vitamin D deficiency as a risk factor for dementia and Alzheimer’s disease: anupdated meta-analysis. BMC Neurol. 2019;19(1):284. doi:10.1186/s12883-019-1500-6
  13. Bianchi VE, Herrera PF, Laura R. Effect of nutrition on neurodegenerative diseases. A systematic review.Nutr Neurosci. Published online November 4, 2019. doi:10.1080/1028415X.2019.1681088
  14. Grodzicki W, Dziendzikowska K. The role of selected bioactive compounds in the prevention of Alzheimer’s disease. Antioxidants. 2020;9(3):229. doi:10.3390/antiox9030229
  15. AlAmmar WA, Albeesh FH, Ibrahim LM, Algindan YY, Yamani LZ, Khattab RY. Effect of omega-3 fatty acids and fish oil supplementation on multiple sclerosis: a systematic review. Nutr Neurosci. Published online August 28, 2019. doi:10.1080/1028415X.2019.1659560
  16. Wlodarek D. Role of ketogenic diets in neurodegenerative diseases (Alzheimer’s disease and Parkinson’s disease). Nutrients. 2019;11(1):169. doi:10.3390/nu11010169
  17. Chauhan A, Chauhan V. Beneficial effects of walnuts on cognition and brain health. Nutrients. 2020;12(2):550. doi:10.3390/nu12020550
  18. Valls-Pedret C, Sala-Vila A, Serra-Mir M, et al. Mediterranean diet and age-related cognitive decline: a randomized clinical trial. JAMA Intern Med. 2015;175(7):1094-1103. doi:10.1001/jamainternmed.2015.1668
  19. Meng X, Zhou J, Zhao CN, Gan RY, Li HB. Health benefits and molecular mechanisms of resveratrol: a narrative review. Foods. 2020;9(3):340. doi:10.3390/foods9030340
  20. Huhn S, Beyer F, Zhang R, et al. Effects of resveratrol on memory performance, hippocampus connectivity and microstructure in older adults – a randomized controlled trial. Neuroimage. 2018;174:177-190. doi:10.1016/j.neuroimage.2018.03.023
  21. Evans HM, Howe PR, Wong RH. Effects of resveratrol on cognitive performance, mood and cerebrovascular function in post-menopausal women: a 14-week randomised placebo-controlled intervention trial. Nutrients. 2017;9(1):27. doi:10.3390/nu9010027
  22. Liu H, Ye M, Guo H. An updated review of randomized clinical trials testing the improvement of cognitive function of Ginkgo biloba extract in healthy people and Alzheimer’s patients. Front Pharmacol. 2020;10:1688. doi:10.3389/fphar.2019.01688
  23. Power R, Coen RF, Beatty S, et al. Supplemental retinal carotenoids enhance memory in healthy individuals with low levels of macular pigment in a randomized, double-blind, placebo-controlled clinical trial. J Alzheimers Dis. 2018;61(3):947-961. doi:10.3233/JAD-170713
  24. Lee DH, Chon J, Kim Y, et al. Association between vitamin D deficiency and cognitive function in the elderly Korean population: a Korean frailty and aging cohort study. Medicine (Baltimore). 2020;99(8):e19293. doi:10.1097/MD.0000000000019293
  25. Feige J, Moser T, Bieler L, Schwenker K, Hauer L, Sellner J. Vitamin D supplementation in multiple sclerosis: a critical analysis of potentials and threats. Nutrients. 2020;12(3):783. doi:10.3390/nu12030783
  26. Kouchaki E, Afarini M, Abolhassani J, et al. High-dose ?-3 fatty acid plus vitamin D3 supplementation affects clinical symptoms and metabolic status of patients with multiple sclerosis: a randomized controlled clinical trial. J Nutr. 2018;148(8):1380-1386. doi:10.1093/jn/nxy116
  27. Martínez-Lapiscina EH, Clavero P, Toledo E, et al. Mediterranean diet improves cognition: the PREDIMED-NAVARRA randomised trial. J Neurol Neurosurg Psychiatry. 2013;84(12):1318-1325. doi:10.1136/jnnp-2012-304792
  28. Lee JE, Bisht B, Hall MJ, et al. A multimodal, nonpharmacologic intervention improves mood and cognitive function in people with multiple sclerosis. J Am Coll Nutr. 2017;36(3):150-168. doi:10.1080/07315724.2016.1255160
  29. Ota M, Matsuo J, Ishida I, et al. Effects of a medium-chain triglyceride-based ketogenic formula on cognitive function in patients with mild-to-moderate Alzheimer’s disease. Neurosci Lett. 2019;690:232-236. doi: 10.1016/j.neulet.2018.10.048

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