Natural Brain Supplements

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 ​
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

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; 288:4056‐4065.
  • 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

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/S0007114517001994. 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

References

  • Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ and Costantini LC. Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr Metab (Lond). 2009; 6:31.

Melatonin

Goals

  • Melatonin can be a short term treatment for trouble falling asleep as part of optimizing sleep to maximize brain health
  • Limited data suggest that sustained release forms of low dose melatonin may help sustain sleep in older adults with memory loss

Methods

  • Melatonin should be used ‘as needed’ for several nights or intermittently over weeks, but should not be used every night or long term
  • If trouble falling asleep, take melatonin 0.5-3 mg 45 minutes before bedtime
  • Try to use the lowest dose that will work for you, starting with 0.5 mg. Repeat the dose after 1 hour if you are still awake, to a maximum of 3 mg nightly
  • If 0.5 mg was not enough to work, then the next night start with 1 mg and repeat the process of the night before until you settle on a lowest effective dose for you
  • If you have trouble with waking in the middle of the night, consider a time released version of melatonin (see resources below)
  • Short term use (days to weeks) appears to be safe for adults

Cautions

  • Drowsiness, impaired balance, impaired alertness are likely effects for 6 hours after use with regular melatonin, and even longer for extended release melatonin
  • Some forms of melatonin contain higher doses than necessary or helpful (e.g., 5 mg or more). The lower doses of 1-3 mg are less likely to cause side effects
  • If a lower dose does not work, then there may be another problem causing your sleeplessness
  • Use of melatonin simultaneous with other sleeping pills can lead to increased risk of excessive sedation, mental or physical slowing, loss of balance, and falls
  • Melatonin may affect hormone levels (e.g., testosterone and/or estrogen), insulin action in non-diabetics, and change blood pressure
  • Long-term use of melatonin is associated with increased risk of fractures, thus, should be used only as needed for short periods of time
  • May not be as effective for jet lag, shift work, or general insomnia in adults and older adults
  • Touted as an ‘anti-aging’ supplement but melatonin levels may not actually drop with aging
  • Costs can range 100-fold, so compare products and prices

Rationale

  • Melatonin triggers sleep
  • As exposure to light decreases in the afternoon and into night, levels of melatonin increase, and vis versa (as light increases in the morning, melatonin level decreases)
  • Melatonin is a hormone (N-acetyl-5-methoxytryptamine) produced by a part of the brain called the pineal gland, which is involved in regulation of sleep-wake cycle (the circadian rhythm)
  • Melatonin in the body is produced from the amino acid tryptophan. Supplements of melatonin is identical but typically synthetic or extracted from plants
  • Melatonin shows promise in the treatment of people withdrawing from sleeping medications, diabetes, schizophrenia, Alzheimer’s disease, Parkinson’s disease, and hospitalized patients
  • May also be helpful for reducing symptoms of tardive dyskinesia, irritable bowel syndrome, heartburn, cluster headaches, or nicotine withdrawal

Resources

References

  • Costello RB, Lentino CV, Boyd CC, O’Connell ML, Crawford CC, Sprengel ML, Deuster PA. The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature. Nutrition Journal. 2014; 13:106.
  • Frisher M, Gibbons N, Bashford J, Chapman S, Weich S. Melatonin, hypnotics and their association with fracture: a matched cohort study. Age and ageing. 2016.
  • Garfinkel D, Zisapel, N, Wainstein J, Laudon M. Facilitation of Benzodiazepine Discontinuation by Melatonin. JAMA Internal Medicine. 1999;159(20)2456-2460.
  • Polimeni G, Esposito E, Bevelacqua V, Guarneri C and Cuzzocrea S. Role of melatonin supplementation in neurodegenerative disorders. Front Biosci (Landmark Ed). 2014; 19:429‐446.
  • Urrestarazu E, Iriarte J. Clinical management of sleep disturbances in Alzheimer’s disease: current and emerging strategies. Nature and Science of Sleep. 2016; 8:21-33.
  • Wade AG, Farmer M, Harari G, Fund N, Laudon M, Nir T, Frydman‐Marom A and Zisapel N. Add‐on prolonged‐release melatonin for cognitive function and sleep in mild to moderate Alzheimer’s disease: a 6‐month, randomized, placebo-controlled, multicenter trial. Clin Interv Aging. 2014; 9:947‐961.

Pantothenic acid

Goals

  • Improve focus/concentration

Methods

  • Pantothenic acid supplementation

Reasoning

  • Pantothenic acid is required for acetylcholine synthesis, which is the neurotransmitter boosted by donepezil (Aricept) and similar FDA approved drugs for AD

Resveratrol

Goals

  • Increase SirT1 function

Methods

  • Consider taking Resveratrol supplement

Cautions

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

References

  • Theendakara V, Patent A, Peters Libeu CA, Philpot B, Flores S, Descamps O, Poksay KS, Zhang Q, Cailing G, Hart M, John V, Rao RV and Bredesen DE. Neuroprotective Sirtuin ratio reversed by ApoE4. Proc Natl Acad Sci U S A. 2013; 110:18303‐18308.

Vitamin B-6

Goal

  • B-6 (pyridoxine) level 60-100 mcg/L

Methods

  • Check blood level of B-6, then supplement if needed or increase dietary intake of B-6
  • Dietary sources of Vitamin B-6 include fish, beef liver and other organ meats, potatoes and other starchy vegetables, and fruit (other than citrus). In the United States, adults obtain most of their dietary vitamin B-6 from fortified cereals, beef, poultry, starchy vegetables, and some non-citrus fruits
  • Pyridoxal-5-Phosphate (P5P), the activated form of Vitamin B-6, is preferred for brain health over ‘regular’ B-6 supplements
  • Complex B-Vitamins can be considered, and should be remembered, as a B-6 source (and not duplicated with individual B-Vitamin supplements)

Cautions

  • Supplements may not be necessary and may be harmful (e.g., mega-high dose B-vitamins may lead to cataracts)
  • B-6 can typically be obtained in sufficient amounts from the diet
  • The official FDA “Upper Tolerable Limit” of B-6 for adults is 100 mg/day, but the European Food Safety Authority recommends a 25 mg/day limit
  • Excessive B-6 intake/too high levels have been related to nerve damage (peripheral neuropathy) and lung cancer (among male smokers)
  • 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 25 mg/day of B-6 (House et al., 2010)

Reasoning

  • Vitamin B-6, also called pyridoxine, is a water-soluble nutrient that is part of the B vitamin family
  • B vitamins, including vitamin B-6, help support adrenal function, the nervous system, and metabolism
  • Maintenance of adequate vitamin B-6 status might help to prevent the development of diabetes in aging and depression

Resources

Consumberlab.com review of Vitamin B supplements
LifeExtension BioActive Complete B-Complex capsules

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.
  • Oxenkrug G, Ratner R, Summergrad P. Kynurenines and vitamin B6: link between diabetes and depression. J Bioinform Diabetes. 2013 Sep 14;1(1). PMID: 25401165; PMCID: PMC4229017.
  • 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/S0007114517001994. PubMed PMID: 28820082.

Vitamin B-12

Goal

  • B-12 level 500-1500 pg/ml

Methods

  • Check blood level of B-12 (+/- methylmalonic acid [MMA]), then supplement if needed or increase dietary intake of B-12
  • Vitamin B-12 is naturally found in animal products, including fish, meat, poultry, eggs, milk, and milk products. Vitamin B-12 is generally not present in plant foods, but fortified breakfast cereals are a readily available source of vitamin B-12 with high bioavailability for vegetarians
  • Methylcobalamin (Me-B12), the activated form, is preferred for brain health over ‘regular’ B-12 supplements
  • Complex B-Vitamins can be considered, and should be remembered, as a B-12 source (and not duplicated with individual B-Vitamin supplements)

Cautions

  • Supplements may not be necessary and may be harmful (e.g., mega-high dose B-vitamins may lead to cataracts)
  • FDA has not set any “upper tolerable limit” for B-12, but 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 1,000 mcg/day of B-12 (House et al., 2010)
  • Excessive B-12 intake/too high levels have been related to acne, rosacea, and lung cancer (among male smokers)

Reasoning

  • Low B-12 levels < 350 are associated with memory loss and anemia

Resources

Consumberlab.com review of Vitamin B12 supplements
Solgar, sublingual Methylcobalamin (Vitamin B12) 1000 mcg nuggets
LifeExtension BioActive Complete B-Complex capsules

References

  • Tangney CC, Tang Y, Evans DA and Morris MC. Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline. Neurology. 2009; 72:361?367.
  • 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/S0007114517001994. PubMed PMID: 28820082.

Vitamin D3

Goals

  • Vitamin D3 (25OH-D3) level of 50-100 ng/ml

Methods

  • Check blood level, then supplement if needed or increase dietary intake
  • Vitamin D3 supplement 500-5000 IU, depending on lab levels – recheck lab level in 6 weeks
  • Consider adding K2 supplement to help reduce any risk of toxicity

References

  • Annweiler, C., Dursun, E., Feron, F., Gezen-Ak, D., Kalueff, A.V., Littlejohns, T., Llewellyn, D.J., Millet, P., Scott, T., Tucker, K.L., Yilmazer, S., Beauchet, O., 2015. ‘Vitamin D and cognition in older adults’: updated international recommendations. J Intern Med 277, 45-57.
  • Littlejohns TJ, Henley WE, Lang IA, Annweiler C, Beauchet O, Chaves PH, Fried L, Kestenbaum BR, Kuller LH, Langa KM, Lopez OL, Kos K, Soni M, et al. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 2014.

Zinc: Copper Ratio

Goals

  • Optimize zinc:free copper ratio (higher Zinc, lower Copper)

Methods

  • Check RBC zinc or serum zinc (less sensitive) level for deficiency
  • Identify and treat reversible causes of low zinc (e.g., vegetarian diet without supplementation, use of proton pump inhibitors, adrenal stress, diabetes, alcohol use, toxic exposure, intestinal parasites, or aging)
  • Supplementation depends on the lab values obtained at baseline and with monitoring
  • If needed, generally supplement with Zinc 50 mg or less each day

Cautions

  • Zinc supplementation can lower copper levels (which can be monitored by measuring either serum ceruloplasmin or serum copper lab testing)
  • Definitive evidence for benefit lacking; large, expensive definitive trial unlikely

Reasoning

  • Zinc is a co-factor for over 300 enzymes
  • Zinc deficiency relates to chronic inflammation, insulin resistance, hormone signaling, mitochondrial dysfunction

References

  • Bredesen DE. Metabolic profiling distinguishes three subtypes of Alzheimer’s disease. Aging. 2015; 595-600.
  • Brewer GJ and Kaur S. International journal of Alzheimer’s disease. 2013.Zinc deficiency and zinc therapy efficacy with reduction of serum free copper in Alzheimer’s disease.