Natural Nutritional Supplements

Natural Brain Supplements

by David Merrill

Supplements are used to optimize the levels of micronutrients in the body linked to cognitive health.

While supplements have an incomplete evidence base, a number of micronutrients are associated with healthy brain aging and most likely act in concert with many, many additional factors including a brain healthy diet. We are careful to provide individualized recommendations balancing risks/benefits for each supplement.

Taking supplements without proper medical supervision and monitoring may be dangerous to health. It is important to note that patients need to confirm with their treating physician(s) that their health is suitable to begin taking supplement products (kidney disease, bleeding, heart, or other health conditions).

Methodology

• Check blood levels of measurable supplements such as Vitamin B12, Vitamin D, etc. during clinic consultation
  • Replenish deficiencies and supplement to optimal levels for brain health
• Consider supplementation with non-measurable but generally-recognized-as-safe supplements
• Supplement choice can be discussed during clinic consultations
  • Contents and purity verified by Consumerlab.com and NSF
  • Manufactured with GMP
  • Ingredients largely sourced from scientific producers who have completed research studies and clinical trials
  • Brain-relevant combination products available
• Consider use of ConsumerLab.com, NSF.org, or similar independent sites when considering buying a new supplement

The initial report and recommendations are discussed with the patient at a feedback session with the patient and available caregiver(s). Brief quarterly follow-up assessments (e.g., every 3 months) are recommended. In addition, a full reassessment is recommended in 6-12 months’ time with repeat volumetric MRI and NP testing to monitor the course of the patient’s brain health and function as necessary.

Useful Resources

• Consumerlab.com
  • Independent testing of commercially available supplements
  • Continual review and critique of evidence base for many supplements
• NSF– The Public Health and Safety Organization
  • Certifies dietary supplement producers and products
  • Check compliance with Good Manufacturing Practices (GMP)

Antioxidants

Goals

• Increase antioxidant levels

Methods

• Dietary sources: berries, nuts, beans, artichokes
• Trace minerals needed for antioxidant enzymes: Cu, Fe, Mn, Se, and Zn
• Mixed tocopherols
• Tocotrienols
• NAC
• Ascorbate
• Alpha-lipoic acid

Reasoning

• Definitive evidence for individual antioxidants slowing dementia progression is lacking
• However, several large population studies have shown correlations between antioxidant intake and lower dementia risk and/or better cognitive function
• Example: Dietary intake of berries high in flavonoids (e.g., blueberries, strawberries) was associated with slower rates of cognitive decline in the Nurse’ Health Study
• Basic science studies show antioxidants protect the brain against damage

Resources

• MIND Diet

References

• Masaki, K.H., Losonczy, K.G., Izmirlian, G., Foley, D.J., Ross, G.W., Petrovitch, H., Havlik, R., White, L.R., 2000. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 54, 1265-1272.
• Parachikova A, Green KN, Hendrix C and LaFerla FM. Formulation of a medical food cocktail for Alzheimer’s disease: beneficial effects on cognition and neuropathology in a mouse model of the disease. PLoS One. 2010; 5:e14015.
• Dysken, M.W., et al., 2014. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. Jama 311, 33-44.
• Basambombo, L.L., Carmichael, P.-H., Côté, S., Laurin, D., 2017. Use of Vitamin E and C Supplements for the Prevention of Cognitive Decline. Annals of Pharmacotherapy 51, 118-124.

Ashwagandha

Goals

• Reduction of amyloid beta and inflammation through ashwagandha supplement

Methods

• Ashwagandha (withania somnifera) supplementation

Resources

• Sensoril in Life Extension Cognitex with Brain Shield or Ashwagandha supplement

References

• Sehgal N, Gupta A, Valli RK, Joshi SD, Mills JT, Hamel E, Khanna P, Jain SC, Thakur SS and Ravindranath V. Withania somnifera reverses Alzheimer’s disease pathology by enhancing low‐density lipoprotein receptor‐related protein in liver. Proc Natl Acad Sci USA. 2012; 109:3510‐3515.

Bacopa (bacopa monniera)

Goals

• Cognitive enhancement through dietary supplements

Methods

• Bacopa (bacopa monniera) supplementation

Resources

• Bacognize in Life Extension Cognitex with Brain Shield or Bacopa supplement

References

• Zanotta D, Puricelli S and Bonoldi G. Cognitive effects of a dietary supplement made from extract of Bacopa monnieri, astaxanthin, phosphatidylserine, and vitamin E in subjects with mild cognitive impairment: a noncomparative, exploratory clinical study. Neuropsychiatr Dis Treat. 2014; 10:225‐230.

Citicoline

Goals

• Preserve existing synapses and promote formation of new synapses

Methods

• Citicoline 600-2000 mg daily – supplement precursor for phosphatidylcholine

Cautions

• Safety of long-term use of citicoline not definitively estabilished
• Definitive evidence for benefit lacking

Rationale

• Protect against cerebrovascular disease/damage
• Increase levels of phosphatides and of specific pre- or post-synaptic proteins
• Increase release of neurotransmitters (e.g., acetylcholine, dopamine)

References

• Cansev M, Wurtman RJ, Sakamoto T and Ulus IH. Oral administration of circulating precursors for membrane phosphatides can promote the synthesis of new brain synapses. Alzheimers Dement. 2008; 4:S153-168.

Curcumin

Reduction of inflammation and amyloid beta through daily curcumin supplementation

Methods

• Take a daily curcumin supplement
• Important to use a supplement independently tested for purity and content

Cautions

• Definitive evidence for benefit lacking; but the large definitive trials are unlikely to be completed due to expense
• Curcumin should be taken with caution/monitoring by your doctor in the following settings: diabetes (i.e., may lower blood sugar levels), high blood pressure (i.e., may impact level of beta blocker or other blood pressure medications), use of blood thinners (exacerbated by the curcumin absorption enhancer piperine);history of gallstones, kidney stones, or organ transplant; use of medications metabolized by liver enzyme CYP3A4, or use of an MAO inhibitor; effects on pregnancy or nursing unknown
• Must take with a meal containing fats or oils (to enhance gut absorption of curcumin)
• Further consideration of this supplement and/or choice of supplements can be discussed during consultation

Resources

• ConsumerLab.com offers an in depth review and testing of curcumin supplements
• Swanson Ultra Turmeric Phytosome (with Meriva, which has 29x increased absorption)
• Life Extension Super Bio-Curcumin (with BCM-95, which has 7x increased absorption)
• Doctor’s Best High Absorption Curcumin (no absorption enhancer, but with piperine to decrease breakdown)
• NOW Curcumin (no absorption enhancer)

References

• Baum, L., Lam, C.W., Cheung, S.K., Kwok, T., Lui, V., Tsoh, J., Lam, L., Leung, V., Hui, E., Ng, C., Woo, J., Chiu, H.F., Goggins, W.B., Zee, B.C., Cheng, K.F., Fong, C.Y., Wong, A., Mok, H., Chow, M.S., Ho, P.C., Ip, S.P., Ho, C.S., Yu, X.W., Lai, C.Y., Chan, M.H., Szeto, S., Chan, I.H., Mok, V., 2008. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol 28, 110-113.
• Begum AN, Jones MR, Lim GP, Morihara T, Kim P, Heath DD, Rock CL, Pruitt MA, Yang F, Hudspeth B, Hu S, Faull KF, Teter B, et al. Curcumin structure‐function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer’s disease. J Pharmacol Exp Ther. 2008; 326:196‐208.
• Cox KH, Pipingas A, Scholey AB. Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J Psychopharmacol. 2015 May;29(5):642-51.
• Ma QL, Zuo X, Yang F, Ubeda OJ, Gant DJ, Alaverdyan M, Teng E, Hu S, Chen PP, Maiti P, Teter B, Cole GM and Frautschy SA. Curcumin suppresses soluble tau dimers and corrects molecular chaperone, synaptic, and behavioral deficits in aged human tau transgenic mice. J Biol Chem. 2013; 288:4056‐4055.
• Rainey-Smith SR, Brown BM, Sohrabi HR, Shah T, Goozee KG, Gupta VB, Martins RN. Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults. Br J Nutr. 2016 Jun;115(12):2106-13.
• Sanmukhani J, Satodia V, Trivedi J, Patel T, Tiwari D, Panchal B, Goel A, Tripathi CB. Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial. Phytother Res. 2014 Apr;28(4):579-85.

Fish oil/Omega-3 fatty acids

Goals

• Fish oil supplement 1 gram twice daily

Methods

• Eat fish twice a week
• Take fish oil supplement with high levels of EPA and DHA

Cautions

• Buy via quality sources, as they have been historically tainted with heavy metals.
• Avoid high-mercury fish: Mackerel (King), Marlin, Orange Roughy, Shark, Swordfish, Tilefish, Ahi Tuna

Rational

• Reduce risk of coronary artery disease, dementia, and cognitive decline
• Consumption level correlated with brain structure and connectivity

Folate (Vitamin B-9)

Goal

• Folate serum level 10-25 ng/ml

Methods

• Check blood level of folate, then increase dietary intake of folate or supplement with folic acid, if needed
• Dietary sources of folate include dark leafy greens, asparagus, broccoli, citrus fruits,beans, peas, lentils, avocado, okra, and brussel sprouts
• Methylfolate, the activated form of folic acid, is preferred for brain health over ‘regular’ folic acid supplements, especially with MTHFR mutation (needs identification through gene testing)
• Complex B-Vitamins can be considered, and should be remembered, as a source of folic acid (and not duplicated with individual B-Vitamin supplements)

Cautions

• Supplements may not be necessary and may be harmful
• The official FDA “Upper Tolerable Limit” for adults of folic acid (synthetic Vitamin B-9) is 1,000 mcg/day
• Folic acid supplementation without B-12 supplementation may mask B-12 deficiency associated anemia and cognitive loss
• Long term excessive intake of folic acid has been related to double the risk of prostate cancer (at 1,000 mcg/day) and cataracts
• Diabetes and advanced kidney disease patients have shown worsening of kidney function and increased risk of heart attack, stroke, and death with a B-complex vitamin including 2,500 mcg/day of folic acid (House et al.,2010)

Reasoning

• Vitamin B-9, commonly called folate,is part of the B vitamin family
• Folic acid is the synthetic form of B9, found in supplements and fortified foods, while folate occurs naturally in foods
• Folic acid is crucial for proper brain function and plays an important role in mental and emotional health
• Adequate folate levels have been associated with reduced risk of heart disease, certain cancers (e.g., colon cancer), and for preventing spina bifida during pregnancy

Resources

• Consumberlab.com review of Vitamin B supplements
• Rite-aid and Walgreens Finest Nutrition brand regular folic acid supplements are inexpensive and verified by Consumer Lab as approved
• LifeExtension BioActive Complete B-Complex capsules provide ‘active’ forms of B vitamins

References

• House AA, Eliasziw M, Cattran DC, Churchill DN, Oliver MJ, Fine A, Dresser GK, Spence JD. Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial. JAMA. 2010 Apr 28;303(16):1603-9. doi:10.1001/jama.2010.490. PubMed PMID: 20424250.
• Selin JZ, Lindblad BE, Bottai M, Morgenstern R, Wolk A. High-dose B-vitamin supplements and risk for age-related cataract: a population-based prospective study of men and women. Br J Nutr. 2017 Jul;118(2):154-160. doi: 10.1017/S0007115825357791. PubMed PMID: 28820082.

Magnesium (MgT)

Goals

• Cognitive enhancement through dietary supplements

Methods

• MgT

Resources

• Li W, Yu J, Liu Y, Huang X, Abumaria N, Zhu Y, Xiong W, Ren C, Liu XG, Chui D and Liu G. Elevation of brain magnesium prevents and reverses cognitive deficits and synaptic loss in Alzheimer’s disease mouse model. J Neurosci. 2013; 33:8423‐8441.

Medium Chain Triglycerides

Goals

• Medium chain triglycerides (MCTs) can be used as an alternative energy source by the brain through the formation of ketone bodies (similar to fasting state)

Methods

• Axona
• Coconut oil