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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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22 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!


  14. JP Says:

    Updated 1/6/16:


    Nutrients. 2016 Jan 2;8(1).

    Association between Blood Omega-3 Index and Cognition in Typically Developing Dutch Adolescents.

    The impact of omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) on cognition is heavily debated. In the current study, the possible association between omega-3 LCPUFAs in blood and cognitive performance of 266 typically developing adolescents aged 13-15 years is investigated. Baseline data from Food2Learn, a double-blind and randomized placebo controlled krill oil supplementation trial in typically developing adolescents, were used for the current study. The Omega-3 Index was determined with blood from a finger prick. At baseline, participants finished a neuropsychological test battery consisting of the Letter Digit Substitution Test (LDST), D2 test of attention, Digit Span Forward and Backward, Concept Shifting Test and Stroop test. Data were analyzed with multiple regression analyses with correction for covariates. The average Omega-3 Index was 3.83% (SD 0.60). Regression analyses between the Omega-3 Index and the outcome parameters revealed significant associations with scores on two of the nine parameters. The association between the Omega-3 Index and both scores on the LDST (β = 0.136 and p = 0.039), and the number of errors of omission on the D2 (β = -0.053 and p = 0.007). This is a possible indication for a higher information processing speed and less impulsivity in those with a higher Omega-3 Index.

    Be well!


  15. JP Says:

    Updated 1/30/16:


    Geriatr Gerontol Int. 2016 Jan 28.

    Beneficial effects of dietary docosahexaenoic acid intervention on cognitive function and mental health of the oldest elderly in Japanese care facilities and nursing homes.

    AIM: We examined the effects of the administration of docosahexaenoic acid (DHA)-enriched meals on cognitive function in the oldest elderly with cognitive impairment, such as dementia, living in nursing homes, and on the improvement in caregiver burden at aging agencies.

    METHODS: Participants in elderly care facilities and nursing homes (n = 75; 88.5 ± 0.6 years) were randomized in active and placebo groups. The active group had family-style meals containing an additional 1720 mg of docosahexaenoic acid per day for 12 months. At baseline, and after 6 and 12 months of intervention, cognitive function was assessed using Hasegawa’s Dementia Scale-Revised and the Mini-Mental State Examination; mental health condition was assessed with the Apathy scale and the Zung Self-Rating Depression Scale; caregiver burden was evaluated using Zarit Burden Interview scores; and participants’ serum biochemical factors were measured.

    RESULTS: The participants were suggested to have dementia. After 12 months, the mean change in Mini-Mental State Examination subitem “Registration” score from baseline to month 12 showed a tendency to be greater in the active group than that in the placebo group. Mean changes in the Apathy scale from baseline to month 12 were less, and the changes in the Zung Self-Rating Depression Scale and the total Zarit Burden Interview scores showed a tendency to be lower in the active group than in the placebo group, respectively.

    CONCLUSION: These results suggest that docosahexaenoic acid-enriched meals protect against age-related cognitive decline, and also improve apathy and caregiver burden for the oldest-elderly Japanese with cognitive impairment, such as dementia.

    Be well!


  16. JP Says:

    Updated 02/22/16:


    J Nurs Scholarsh. 2016 Feb 15.

    Effects of Multivitamin Supplements on Cognitive Function, Serum Homocysteine Level, and Depression of Korean With Mild Cognitive Impairment in Care Facilities.

    PURPOSE: To examine effects of multivitamin supplements on cognitive function, serum homocysteine level, and depression of Korean older adults with mild cognitive impairment (MCI) in care facilities.

    DESIGN: A quasi-experimental pretest-posttest control group design was employed.

    METHODS: Forty-eight adults 65 years of age and older with MCI (experimental, n = 24; control, n = 24) who were living in care facilities in Gyeong-gi-do, Korea, were recruited. Multivitamin supplements as experimental treatment consisted of vitamin B6, B12, and folic acid. Multivitamin supplements were taken at a dosage of one pill every day for 12 weeks through the oral route. Measures were Mini Mental State Examination-Korean, serum homocysteine level, and Geriatric Depression Scale Short Form Korea Version. Collected data were analyzed using SPSS version 21.0 statistical software (SPSS Inc., Chicago, IL, USA).

    FINDINGS: There were significant effects of multivitamin supplements on cognitive function (F = 3.624, p = .021), serum homocysteine level (F = 6.974, p = .001), and depression (F = 10.849, p = .001).

    CONCLUSIONS: Multivitamin supplements increased cognitive function, and decreased serum homocysteine level and depression of Korean older adults with MCI in care facilities.

    CLINICAL RELEVANCE: Multivitamin supplements can be utilized for improving cognitive ability and for decreasing depression of Korean older adults with MCI in care facilities.

    Be well!


  17. JP Says:

    Updated 03/18/16:


    Adv Exp Med Biol. 2016;876:319-25. doi: 10.1007/978-1-4939-3023-4_40.

    Effect of the Antioxidant Supplement Pyrroloquinoline Quinone Disodium Salt (BioPQQ™) on Cognitive Functions.

    Pyrroloquinoline quinone (PQQ) is a quinone compound first identified in 1979. It has been reported that rats fed a PQQ-supplemented diet showed better learning ability than controls, suggesting that PQQ may be useful for improving memory in humans. In the present study, a randomized, placebo-controlled, double-blinded study to examine the effect of PQQ disodium salt (BioPQQ™) on cognitive functions was conducted with 41 elderly healthy subjects. Subjects were orally given 20 mg of BioPQQ™ per day or placebo, for 12 weeks. For cognitive functions, selective attention by the Stroop and reverse Stroop test, and visual-spatial cognitive function by the laptop tablet Touch M, were evaluated. In the Stroop test, the change of Stroop interference ratios (SIs) for the PQQ group was significantly smaller than for the placebo group. In the Touch M test, the stratification analyses dividing each group into two groups showed that only in the lower group of the PQQ group (initial score < 70), did the score significantly increase. Measurements of physiological parameters indicated no abnormal blood or urinary adverse events, nor adverse internal or physical examination findings at any point in the study. The preliminary experiment using near-infrared spectrometry (NIRS) suggests that cerebral blood flow in the prefrontal cortex was increased by the administration of PQQ. The results suggest that PQQ can prevent reduction of brain function in aged persons, especially in attention and working memory.

    Be well!


  18. JP Says:

    Updated 06/26/16:


    Mediators Inflamm. 2016;2016:5912146.

    Folic Acid Supplementation Mitigates Alzheimer’s Disease by Reducing Inflammation: A Randomized Controlled Trial.

    Background/Aims. Low serum folate levels can alter inflammatory reactions. Both phenomena have been linked to Alzheimer’s disease (AD), but the effect of folic acid on AD itself is unclear. We quantified folate supplementation’s effect on inflammation and cognitive function in patients with AD over the course of 6 months.

    Methods. Patients newly diagnosed with AD (age > 60 years; n = 121; mild to severe; international criteria) and being treated with donepezil were randomly assigned into two groups with (intervention group) or without (control group) supplemental treatment with folic acid (1.25 mg/d) for 6 months. The Mini-Mental State Examination (MMSE) was administered to all patients at baseline and follow-up, and blood samples were taken before and after treatment. We quantified serum folate, amyloid beta (Aβ), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), plasma homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and the mRNA levels of presenilin (PS), IL-6, and TNFα in leukocytes. Data were analyzed using a repeated-measures mixed model.

    Results. The mean MMSE was slightly increased in the intervention group compared to that in the control group (P < 0.05). Posttreatment, plasma SAM and SAM/SAH levels were significantly higher (P < 0.05), while Aβ 40, PS1-mRNA, and TNFα-mRNA levels were lower in the intervention group than in the control group (P < 0.05). The Aβ 42/Aβ 40 ratio was also higher in the intervention group (P < 0.05).

    Conclusions. Folic acid is beneficial in patients with AD. Inflammation may play an important role in the interaction between folic acid and AD.

    Be well!


  19. JP Says:

    Updated 08/27/16:


    Adv Exp Med Biol. 2016;923:215-22.

    Effects of Antioxidant Supplements (BioPQQ™) on Cerebral Blood Flow and Oxygen Metabolism in the Prefrontal Cortex.

    Pyrroloquinoline quinone (PQQ) is a quinone compound originally identified in methanol-utilizing bacteria and is a cofactor for redox enzymes. At the Meeting of the International Society on Oxygen Transport to Tissue (ISOTT) 2014, we reported that PQQ disodium salt (BioPQQ™) improved cognitive function in humans, as assessed by the Stroop test. However, the physiological mechanism of PQQ remains unclear. In the present study, we measured regional cerebral blood flow (rCBF) and oxygen metabolism in prefrontal cortex (PFC), before and after administration of PQQ, using time-resolved near-infrared spectroscopy (tNIRS). A total of 20 healthy subjects between 50 and 70 years of age were administered BioPQQ™ (20 mg) or placebo orally once daily for 12 weeks. Hemoglobin (Hb) concentration and absolute tissue oxygen saturation (SO2) in the bilateral PFC were evaluated under resting conditions using tNIRS. We found that baseline concentrations of hemoglobin and total hemoglobin in the right PFC significantly increased after administration of PQQ (p < 0.05). In addition, decreases in SO2 level in the PFC were more pronounced in the PQQ group than in the placebo group (p < 0.05). These results suggest that PQQ causes increased activity in the right PFC associated with increases in rCBF and oxygen metabolism, resulting in enhanced cognitive function.

    Be well!


  20. JP Says:

    Updated 08/29/16:


    J Alzheimers Dis. 2016 Aug 24.

    CerefolinNAC Therapy of Hyperhomocysteinemia Delays Cortical and White Matter Atrophy in Alzheimer’s Disease and Cerebrovascular Disease.

    We examined whether using a medical food therapy for hyperhomocysteinemia (HHcy) in patients with Alzheimer’s disease (AD) or cognitive impairment due to cerebrovascular disease (CVD) with Cerefolin®/CerefolinNAC® (CFLN: L-methylfolate, methylcobalamin, and N-acetyl-cysteine) slowed regional brain atrophy. Thirty HHcy patients with AD and related disorders (ADRD) received CFLN (HHcy+CFLN: duration [μ ±  σ] = 18.6±16.1 months); a sub-sample of this group did not receive CFLN for varying periods of time (HHcy+NoCFLN: duration [μ ±  σ] = 12.6±5.6 months). Thirty-seven NoHHcy patients with ADRD did not receive CFLN (NoHHcy+NoCFLN: duration [μ ±  σ] = 13.3±17.7 months). No participant took supplemental B vitamins. Regional brain volumes were measured at baseline and end of study, and covariate-adjusted rates of hippocampal, cortical, and forebrain parenchymal (includes white matter) atrophy were predicted. The HHcy+CFLN group’s hippocampal and cortical atrophy adjusted rates were 4.25 and 11.2 times slower than the NoHHcy+NoCFLN group (p < 0.024). The HHcy+CFLN group’s forebrain parenchyma atrophy rate was significantly slower only for CVD; the rate of slowing was proportional to the degree of homocysteine lowering (p < 0.0001). CFLN was associated with significantly slowed hippocampal and cortical atrophy rates in ADRD patients with HHcy, and forebrain parenchymal atrophy rates in CVD patients with HHcy, and should be further validated.

    Be well!


  21. JP Says:

    Updated 10/08/16:


    J Alzheimers Dis. 2016 Oct 1.

    Effects of DHA Supplementation on Hippocampal Volume and Cognitive Function in Older Adults with Mild Cognitive Impairment: A 12-Month Randomized, Double-Blind, Placebo-Controlled Trial.

    Docosahexaenoic acid (DHA) is important for brain function, and higher DHA intake is inversely correlated with relative risk of Alzheimer’s disease. The potential benefits of DHA supplementation in people with mild cognitive impairment (MCI) have not been fully examined. Our study aimed to determine the effect of DHA supplementation on cognitive function and hippocampal atrophy in elderly subjects with MCI. This was a randomized, double-blind, placebo-controlled trial in Tianjin, China. 240 individuals with MCI aged 65 years and over were recruited and equalized randomly allocated to the DHA or the placebo group. Participants received 12-month DHA supplementation (2 g/day) or corn oil as placebo. Both global and specific subdomains of cognitive function and hippocampal volume were measured at baseline, 6 months, and 12 months. Both changes were analyzed by repeated-measure analysis of variance (ANOVA). This trial has been registered: ChiCTR-IOR-15006058. A total of 219 participants (DHA: 110, Placebo: 109) completed the trial. The change in mean serum DHA levels was greater in the intervention group (+3.85%) compared to the control group (+1.06%). Repeated-measures analyses of covariance showed that, over 12 months, there was a significant difference in the Full-Scale Intelligence Quotient (ηp2 = 0.084; p = 0.039), Information (ηp2 = 0.439; p = 0.000), and Digit Span (ηp2 = 0.375; p = 0.000) between DHA-treated versus the placebo group. In addition, there were significant differences in volumes of left hippocampus (ηp2 = 0.121, p = 0.016), right hippocampus (ηp2 = 0.757, p = 0.008), total hippocampus (ηp2 = 0.124, p = 0.023), and global cerebrum (ηp2 = 0.145, p = 0.032) between the two groups. These findings suggest that DHA supplementation (2 g/day) for 12 months in MCI subjects can significantly improve cognitive function and slow the progression of hippocampal atrophy. Larger, longer-term confirmatory studies are warranted.

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  22. JP Says:

    Updated 10/10/16:


    Ann Pharmacother. 2016 Oct 4.

    Use of Vitamin E and C Supplements for the Prevention of Cognitive Decline.

    BACKGROUND: There are few studies of the association between the use of antioxidant vitamin supplements and the risk of Alzheimer’s disease (AD). Cognitive decline is generally viewed as part of the continuum between normal aging and AD.

    OBJECTIVE: To evaluate whether the use of vitamin E and C supplements is associated with reduced risks of cognitive impairment, not dementia (CIND), AD, or all-cause dementia in a representative sample of older persons ≥65 years old.

    METHODS: Data from the Canadian Study of Health and Aging (1991-2002), a cohort study of dementia including 3 evaluation waves at 5-yearly intervals, were used. Exposure to vitamins E and C was self-reported at baseline in a risk factor questionnaire and/or in a clinical examination.

    RESULTS: The data set included 5269 individuals. Compared with those not taking vitamin supplements, the age-, sex-, and education-adjusted hazard ratios of CIND, AD, and all-cause dementia were, respectively, 0.77 (95% CI = 0.60-0.98), 0.60 (95% CI = 0.42-0.86), and 0.62 (95% CI = 0.46-0.83) for those taking vitamin E and/or C supplements. Results remained significant in fully adjusted models except for CIND. Similar results were observed when vitamins were analyzed separately.

    CONCLUSIONS: This analysis suggests that the use of vitamin E and C supplements is associated with a reduced risk of cognitive decline. Further investigations are needed to determine their value as a primary prevention strategy.

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