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Prescription 2014: Supplement Your Brain

August 14, 2014 Written by JP       [Font too small?]

It’s rare to find someone who is entirely satisfied with how their brain functions. Some people have periodic or persistent episodes of “brain fog”. Others find themselves prone to distraction. Also, complaints about sluggish cognitive processing and memory recall are commonplace in my consulting work. Then, there are those who are relatively pleased with their mental acuity, but would be even happier to have an added edge. In all of these cases and more, certain supplements can make a difference above and beyond the basic measures that most people employ to stay healthy.

My philosophy about dietary supplements requires a brief explanation. I believe that supplements should primarily be used to “supplement” an already healthy lifestyle. This is not to say that they won’t afford some benefit to those who fall short of their dietary, exercise and mind-body goals. They usually do. But, their micro effects tend to be more pronounced when the macro aspects of wellness (diet, mental health practices and physical activity) are in order. Additionally, supplements do not always have to be taken in conventional forms such as capsules, liquid extracts or tablets. Coffee, dark chocolate and red wine are examples of foods which can be strategically used as nutritional supplements.

Over the past year, multiple studies have isolated dietary components which positively affect cognitive functioning and/or impart neuroprotection. For starters, taking a multivitamin rich in B vitamins along with a source of caffeine has been shown to increase brain activity “in areas associated with working memory and attentional processing”. Related research indicates that B vitamins and caffeine support brain function and health by reducing the levels of homocysteine, a conditionally harmful amino acid, while enhancing the consolidation of memories. Resveratrol, an antioxidant found in red wine, has likewise shown promise by encouraging cerebral blood flow, improving memory performance and lowering long-term blood sugar concentrations (HbA1c). The dosages used in the resveratrol studies (200 – 500 mg/day) are much higher than what can be realistically acquired from drinking red wine. In terms of documented neuroprotection, current trials report that omega-3 fatty acids, as found in fish and krill oil, improve cognitive functioning in seniors and preserve brain volume. Additionally, a two-year study in the May 2014 issue of Stroke, reports that supplementing with 200 mg daily of palm tocotrienols, a rare form of Vitamin E, protects against the development of white matter lesions – damage related to “mini-stokes” and Multiple Sclerosis.

If after reading this column, you decide to supplement your brain, I would begin by taking a high-potency multivitamin/mineral. This generally contains a large enough dosage of the essential B vitamins necessary to keep homocysteine levels in check. Typically, I don’t encourage the use of supplemental caffeine. However, I think the evidence for coffee’s role in cognitive enhancement and neuroprotection is quite strong. That’s why I often recommend coffee to those who tolerate it well. Eating a few-to-several weekly servings of clean, cold water fish may be enough to protect your brain from age related atrophy and decline. Having said that, I supplement with fish oil daily as a preventive measure. Again, the data on fish oil justifies its use in many cases. As far as resveratrol and tocotrienols go, I get a low-to-moderate dosage in my multivitamin. If the time comes when I need additional support for my brain, I wouldn’t hesitate to match the dosages used in the referenced trials.

Note: Please check out the “Comments & Updates” section of this blog – at the bottom of the page. You can find the latest research about this topic there!

To learn more about the studies referenced in today’s column, please click on the following links:

Study 1 - Acute Effects of Different Multivitamin Mineral Preparations With and (link)

Study 2 - B Vitamin Supplementation Improves Cognitive Function in the Middle … (link)

Study 3 - Post-Study Caffeine Administration Enhances Memory Consolidation (link)

Study 4 - Acute Caffeine Administration Impact on Working Memory-Related (link)

Study 5 – Clinical Investigation of the Protective Effects of Palm Vitamin E (link)

Study 6 - Classification and Prediction of Clinical Diagnosis of Alzheimer’s Disease(link)

Study 7 - Effects of Krill Oil Containing N-3 Polyunsaturated Fatty Acids in (link)

Study 8 – Association of Fish Oil Supplement Use w/ Preservation of Brain Volume (link)

Study 9 - Effects of Resveratrol on Memory Performance, Hippocampal Functional (link)

Study 10 - Effects of Resveratrol on Cerebral Blood Flow Variables and Cognitive (link)

Palm Tocotrienols Protect Against Brain Lesions (WML)

Source: Stroke. 2014 May;45(5):1422-8. (link)

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13 Comments & Updates to “Prescription 2014: Supplement Your Brain”

  1. Iggy Dalrymple Says:

    I’m a sucker for brain & anti-dementia supplements. Take Magtein magnesium threonate, MitoQ, and Longvida….all of which claim to have greatly improved ability to cross the brain blood barrier. Also take resveratrol and alpha-lipoic acid, but no multi. Can’t say I feel any different but I’m trying to stave off dementia and Alzheimer’s. My 75 yr old brain seems to be hanging in there. Have less trouble than my wife in searching for words and names, but have my moments.

  2. Iggy Dalrymple Says:

    Forgot to add. Am slow to get going in the morning. In order to muster the energy to walk early to avoid heat, I take “5 hr energy drink”. It really seems to help. My regular coffee is too hot to drink and take off early.

  3. liverock Says:

    I would choose a B multivitamin with the active L-5 Methylfolate and Methyl B12. Cheaper multi’s use synthetic folic acid and cyanocobalamin B12 which some people find hard to convert to the active forms.

    Low Vitamin B12 has also been shown to shrink brain volume and cause cognitive problems.


    Its also advisable to keep Vitamin D levels above 70nml to prevent dementia, according to a recent Exeter University study.

    Iggy should be alright with all that walking in the Florida sunshine!

  4. JP Says:

    Hi Iggy,

    5 Hour Energy contains relatively high levels of several B vitamins – B3, B6, B12 and folic acid. The amounts contained in the formula should be enough to affect homocysteine concentrations.

    Be well!


  5. JP Says:

    Hi Liverock,

    Yes, that’s still the case. However, a few of the newer generation supplements are beginning to buck this trend. One example:


    An interesting, recent review about B12 suggests a combination of B12 forms may be ideal:


    Eur J Clin Nutr. 2014 Aug 13. doi: 10.1038/ejcn.2014.165. [Epub ahead of print]

    Treatment of vitamin B12 deficiency-Methylcobalamine? Cyancobalamine? Hydroxocobalamin?-clearing the confusion.

    Thakkar K1, Billa G2.

    Vitamin B12 (cyancobalamin, Cbl) has two active co-enzyme forms, methylcobalamin (MeCbl) and adenosylcobalamin (AdCbl). There has been a paradigm shift in the treatment of vitamin B12 deficiency such that MeCbl is being extensively used and promoted. This is despite the fact that both MeCbl and AdCbl are essential and have distinct metabolic fates and functions. MeCbl is primarily involved along with folate in hematopiesis and development of the brain during childhood. Whereas deficiency of AdCbl disturbs the carbohydrate, fat and amino-acid metabolism, and hence interferes with the formation of myelin. Thereby, it is important to treat vitamin B12 deficiency with a combination of MeCbl and AdCbl or hydroxocobalamin or Cbl. Regarding the route, it has been proved that the oral route is comparable to the intramuscular route for rectifying vitamin B12 deficiency.

    Be well!


  6. Iggy Dalrymple Says:

    Also take fisetin but had forgotten why. Maybe if I had taken more fisetin, I’d remember why I was taking it.

  7. JP Says:

    Ha! Maybe. ;-) Fisetin supposedly crosses the blood brain barrier and, in animal models, has demonstrated evidence of neuroprotection. I haven’t found any human studies though. But, it’s one of the reasons I eat organic strawberries on a regular basis. :-)


    Be well!


  8. JP Says:

    Update: American ginseng shows promise …


    Hum Psychopharmacol. 2015 Mar;30(2):108-22.

    Improved working memory performance following administration of a single dose of American ginseng (Panax quinquefolius L.) to healthy middle-age adults.

    OBJECTIVE: A ginsenoside-rich extract of American ginseng (Panax quinquefolius L.), Cereboost(TM) , was previously shown to improve working memory and mood in healthy young individuals. The present study represented a partial replication investigating whether these effects extended to healthy middle-aged individuals.

    METHODS: Fifty-two healthy volunteers (40-60 years old, mean age 51.63) received 200 mg of P. quinquefolius or a matching placebo according to a double-blind, placebo-controlled, balanced, crossover design. The Cognitive Drug Research battery and the Computerised Mental Performance Assessment System were used to evaluate cognitive performance at baseline then 1, 3 and 6 h following treatment. Blood glucose and mood were co-monitored.
    Compared with placebo, P. quinquefolius improved cognitive performance on ‘Working Memory’ factor at 3 h. Similar effects were observed in one of the two tasks making up this factor, spatial working memory. There were no significant effects on mood or blood glucose levels.

    CONCLUSIONS: These data confirm that P. quinquefolius can acutely benefit working memory and extend the age range of this effect to middle-aged individuals. These changes are unlikely to be underpinned by modulation of blood glucose in this population.

    Be well!


  9. JP Says:

    Update 04/20/15:


    Am J Clin Nutr April 2015

    Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial

    Background: Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia.

    Objective: We investigated whether plasma ω-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG).

    Design: This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline ω-3 fatty acid concentrations.

    Results: There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3 fatty acids (>590 μmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (<390 μmol/L). High baseline ω-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group.

    Conclusions: The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids. It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials.

    Be well!


  10. JP Says:

    Update 05/12/15:


    JAMA Intern Med. 2015 May 11.

    Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial.

    Importance: Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking.

    Objective: To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet.

    Design, Setting, and Participants: Parallel-group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233 women [52.1%]; mean age, 66.9 years), at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1, 2003, through December 31, 2009. All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study.

    Interventions: Participants were randomly assigned to a Mediterranean diet supplemented with extravirgin olive oil (1 L/wk), a Mediterranean diet supplemented with mixed nuts (30 g/d), or a control diet (advice to reduce dietary fat).

    Main Outcomes and Measures: Rates of cognitive change over time based on a neuropsychological test battery: Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT), Animals Semantic Fluency, Digit Span subtest from the Wechsler Adult Intelligence Scale, Verbal Paired Associates from the Wechsler Memory Scale, and the Color Trail Test. We used mean z scores of change in each test to construct 3 cognitive composites: memory, frontal (attention and executive function), and global.

    Results: Follow-up cognitive tests were available in 334 participants after intervention (median, 4.1 years). In multivariate analyses adjusted for confounders, participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT (P = .049) and Color Trail Test part 2 (P = .04) compared with controls; no between-group differences were observed for the other cognitive tests. Similarly adjusted cognitive composites (mean z scores with 95% CIs) for changes above baseline of the memory composite were 0.04 (-0.09 to 0.18) for the Mediterranean diet plus olive oil, 0.09 (-0.05 to 0.23; P = .04 vs controls) for the Mediterranean diet plus nuts, and -0.17 (-0.32 to -0.01) for the control diet. Respective changes from baseline of the frontal cognition composite were 0.23 (0.03 to 0.43; P = .003 vs controls), 0.03 (-0.25 to 0.31), and -0.33 (-0.57 to -0.09). Changes from baseline of the global cognition composite were 0.05 (-0.11 to 0.21; P = .005 vs controls) for the Mediterranean diet plus olive oil, -0.05 (-0.27 to 0.18) for the Mediterranean diet plus nuts, and -0.38 (-0.57 to -0.18) for the control diet. All cognitive composites significantly (P < .05) decreased from baseline in controls.

    Conclusions and Relevance: In an older population, a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function.

    Be well!


  11. JP Says:

    Updated 08/10/15:


    Alzheimers Res Ther. 2015 Jul 24;7(1):51.

    Effects of Souvenaid on plasma micronutrient levels and fatty acid profiles in mild and mild-to-moderate Alzheimer’s disease.

    INTRODUCTION: Circulating levels of uridine, selenium, vitamins B12, E and C, folate, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been shown to be lower in patients with Alzheimer’s disease (AD) than in healthy individuals. These low levels may affect disease pathways involved in synapse formation and neural functioning. Here, we investigated whether, and to what extent, circulating levels of micronutrients and fatty acids can be affected by oral supplementation with Souvenaid (containing a specific nutrient combination), using data derived from three randomized clinical trials (RCT) and an open-label extension (OLE) study with follow-up data from 12 to 48 weeks.

    METHODS: Subjects with mild (RCT1, RCT2) or mild-to-moderate AD (RCT3) received active or control product once daily for 12-24 weeks or active product during the 24-week OLE following RCT2 (n = 212-527). Measurements included plasma levels of B vitamins, choline, vitamin E, selenium, uridine and homocysteine and proportions of DHA, EPA and total n-3 long-chain polyunsaturated fatty acids in plasma and erythrocytes. Between-group comparisons were made using t tests or non-parametric alternatives.

    RESULTS: We found that 12-24-week active product intake increased plasma and/or erythrocyte micronutrients: uridine; choline; selenium; folate; vitamins B6, B12 and E; and fatty acid levels of DHA and EPA (all p < 0.001). In the OLE study, similar levels were reached in former control product/initial active product users, whereas 24-week continued active product intake showed no suggestion of a further increase in nutrient levels.

    CONCLUSIONS: These data show that circulating levels of nutrients known to be decreased in the AD population can be increased in patients with mild and mild-tomoderate AD by 24-48-week oral supplementation with Souvenaid. In addition, to our knowledge, this is the first report of the effects of sustained dietary intake of uridine monophosphate on plasma uridine levels in humans. Uptake of nutrients is observed within 6 weeks, and a plateau phase is reached for most nutrients during prolonged intake, thus increasing the availability of precursors and cofactors in the circulation that may be used for the formation and function of neuronal membranes and synapses in the brain.

    Be well!


  12. JP Says:

    Updated 08/10/15:


    Clin Nutr. 2015 Jul 16. pii: S0261-5614(15)00178-8.

    Vitamin D supplementation reduces depressive symptoms in patients with chronic liver disease.


    Vitamin D deficiency and depression frequently occur in patients with chronic liver diseases (CLD). Depression has recently been inversely associated with vitamin D in a meta-analysis, and vitamin D receptor is expressed in brain. This pilot study investigates whether vitamin D replacement ameliorates depressive symptoms in CLD patients and consists of a cross-sectional and an interventional analysis.

    Overall, 111 patients with CLD were included in the cross-sectional analysis. The Beck Depression Inventory II (BDI-II) was used to assess depression. Chemiluminescence immunoassay and LC-MS/MS quantified serum 25-hydroxyvitamin D levels. For the interventional analysis, 77 patients with inadequate vitamin D concentrations received 20,000 IU vitamin D per week for six months. The final follow-up was carried out six months post supplementation.

    In the cross-sectional analysis, 81% of patients (median age 55 years, 47% women) had inadequate baseline vitamin D levels (<30 ng/ml), and 31% presented with depressive symptoms (BDI-II score ≥14). Depression severity correlated inversely with vitamin D level in depressed patients (β = -0.483, P = 0.004). Depression scores improved significantly from baseline in depressed patients after three and six months (P = 0.003 and P = 0.004, respectively) of supplementation, with vitamin D levels increasing to normal (P < 0.0001). Subgroup analyses revealed this anti-depressant effect of vitamin D to occur predominantly in women. The final follow-up showed increases in median BDI-II scores in the setting of decreased vitamin D levels.

    Vitamin D levels correlated with BDI-II scores, and vitamin D replacement significantly improved depressive symptoms in women with CLD. Adjuvant vitamin D may be considered in these patients.

    Be well!


  13. JP Says:

    Updated 09/28/15:


    J Alzheimers Dis. 2015 Sep 4.

    A Nutritional Formulation for Cognitive Performance in Mild Cognitive Impairment: A Placebo-Controlled Trial with an Open-Label Extension.

    Thirty-four individuals with mild cognitive impairment were randomized for 6 months to a nutraceutical formulation (NF: folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or indistinguishable placebo, followed by a 6-month open-label extension in which all individuals received NF. The NF cohort improved in the Dementia Rating Scale (DRS; effect size >0.7) and maintained baseline performance in CLOX-1. The placebo cohort did not improve in DRS and declined in CLOX-1, but during the open-label extension improved in DRS and ceased declining in CLOX-1.These findings extend prior studies of NF efficacy for individuals without cognitive impairment and with Alzheimer’s disease.

    Be well!


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