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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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Posted in Alternative Therapies, Memory, Nutritional Supplements

36 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! JP

  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! JP

  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. CONCLUSIONS: 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! JP

  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! JP

  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! JP

  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! JP

  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! JP

  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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  23. JP Says:

    Updated 10/21/16:


    Caspian J Intern Med. 2016 Summer;7(3):188-194.

    The effect of green tea consumption on oxidative stress markers and cognitive function in patients with Alzheimer’s disease: A prospective intervention study.

    BACKGROUND: Alzheimer’s disease (AD) is the most prevalent degenerative disorder of the brain among elderly individuals. Many studies indicate that oxidative stress is an important pathogenic factor which involves oxidizing macromolecules such as DNA, lipids, and proteins in AD. Green tea is a rich source of antioxidant compounds that can remove radical oxygen species. The purpose of this study was to investigate the influence of green tea consumption on markers of oxidative stress in AD.

    METHODS: In this prospective intervention study, 30 patients with severe AD were recruited. The diagnosis of AD was made based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s disease and Related Disorders Association (NINCDS/ADRDA) criteria. Brain magnetic resonance imaging (MRI) and computed tomography (CT) scan as well as Mini-Mental State Examination (MMSE) were performed for all participants in which four green tea pills were administered daily for 2 months (2 g/day in 2 divided doses). The plasma total antioxidant capacity, 8-hydroxy-2′-deoxyguanosine levels (8-OHdG), malondialdehyde (MDA), carbonyl content, and MMSE scores were measured at baseline and at the end of the study period.

    RESULTS: The levels of MDA, 8-OHdG and carbonyl decreased significantly as compared to baseline values (P=0.002, P=0.001 and P=0.037, respectively). Whereas, the total antioxidant capacity of plasma and MMSE scores significantly increased at end point (P=0.000, P=0.043, respectively).

    CONCLUSION: The findings indicate that consumption of green tea for two months by with the improvement of antioxidant system exerts beneficial effect on cognitive function.

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  24. JP Says:

    Updated 11/10/16:


    PLoS One. 2016 Nov 8;11(11):e0165861.

    Meta-Analysis of the Association between Tea Intake and the Risk of Cognitive Disorders.

    BACKGROUND: Alzheimer’s disease is a common neurodegenerative disorder in elderly. This study was aimed to systematically evaluate the association between tea intake and the risk of cognitive disorders by meta-analysis.

    METHODS AND FINDINGS: PubMed, Embase and Wanfang databases were systematically searched and a total of 26 observational studies were included in this study. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated and pooled by using fixed or random effects models according to the degree of heterogeneity.

    RESULTS: The overall pooled analysis indicated that tea intake could significantly reduce the risk of cognitive disorders (OR = 0.65, 95%CI = 0.58-0.73). Subgroup analyses were conducted based on study design, population, frequency of tea drinking and type of cognitive disorders. The results showed that tea drinking was significantly associated with the reduced incidence of cognitive disorders in all of subgroups based on study design and frequency of tea drinking. In particular, tea drinking was inversely associated with the risk of cognitive impairment (CoI), mild cognitive impairment (MCI), cognitive decline and ungrouped cognitive disorders. Moreover, for population subgroups, the significant association was only found in Chinese people.

    CONCLUSION: Our study suggests that daily tea drinking is associated with decreased risk of CoI, MCI and cognitive decline in the elderly. However, the association between tea intake and Alzheimer’s disease remains elusive.

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  25. JP Says:

    Updated 11/20/16:


    Nutrients 2016, 8(11), 736

    Randomized Prospective Double-Blind Studies to Evaluate the Cognitive Effects of Inositol-Stabilized Arginine Silicate in Healthy Physically Active Adults

    Inositol-stabilized arginine silicate (ASI; Nitrosigine®) has been validated to increase levels of arginine, silicon and nitric oxide production. To evaluate potential enhancement of mental focus and clarity, ASI (1500 mg/day) was tested in two double-blind placebo-controlled crossover (DBPC-X) studies using the Trail Making Test (TMT, Parts A and B). In the two studies, healthy males took ASI for 14 and 3 days, respectively. In the first study, after 14 days of dosing, TMT B time decreased significantly from baseline (28% improvement, p = 0.045). In the second study evaluating shorter-term effects, TMT B time decreased significantly compared to placebo (33% improvement, p = 0.024) in a 10-min period. After 3 days of dosing, TMT B time significantly decreased from baseline scores (35% improvement, p < 0.001). These findings show that ASI significantly improved the ability to perform complex cognitive tests requiring mental flexibility, processing speed and executive functioning. Be well! JP

  26. JP Says:

    Updated 11/22/16:


    Evid Based Complement Alternat Med. 2016;2016:4103423.

    Efficacy of Standardized Extract of Bacopa monnieri (Bacognize®) on Cognitive Functions of Medical Students: A Six-Week, Randomized Placebo-Controlled Trial.

    Rationale. Bacopa monnieri, popularly known as Brahmi, has been traditionally used in Ayurveda since ages for its memory enhancing properties. However, data on placebo-controlled trial of Bacopa monnieri on intellectual sample is scarce. Hence this study was planned to evaluate the effect of Bacopa monnieri on memory of medical students for six weeks. Objective. To evaluate the efficacy of Bacopa monnieri on memory of medical students with six weeks’ administration. Method and Material. This was a randomized double blind placebo-controlled noncrossover, parallel trial. Sixty medical students of either gender from second year of medical school, third term, regular batch, were enrolled from Government Medical College, Nagpur, India. Baseline biochemical and memory tests were done. The participants were randomly divided in two groups to receive either 150 mg of standardized extract of Bacopa monnieri (Bacognize) or matching placebo twice daily for six weeks. All baseline investigations were repeated at the end of the trial. Students were followed up for 15 days after the intervention. Results. Statistically significant improvement was seen in the tests relating to the cognitive functions with use of Bacopa monnieri. Blood biochemistry also showed a significant increase in serum calcium levels (still within normal range).

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  27. JP Says:

    Updated 12/18/16:


    Evid Based Complement Alternat Med. 2016;2016:3092828.

    The Effects of Four-Week Multivitamin Supplementation on Mood in Healthy Older Women: A Randomized Controlled Trial.

    Objective. Nutritional deficiencies have been associated with cognitive decline and mood disturbances. Vitamin intake can influence mood and randomized controlled trials have demonstrated that multivitamin supplements are capable of reducing mild symptoms of mood dysfunction. However, few studies have focussed on healthy older women. Methods. This study investigated the effects of four weeks’ multivitamin supplementation on mood in 76 healthy women aged 50-75 years. Mood was assessed before and after intervention in the laboratory using measures of current mood and retrospective experiences of mood over the past week or longer. Mobile phones were used to assess changes in real-time mood ratings, twice weekly in the home. Results. There were no multivitamin-related benefits identified for measures of current mood or reflections of recent mood when measured in the laboratory. In-home assessments, where mood was rated several hours after dose, revealed multivitamin supplementation improved ratings of stress, with a trend to reduce mental fatigue. Conclusions. Over four weeks, subtle changes to stress produced by multivitamin supplementation in healthy older women may not be detected when only pre- and posttreatment mood is captured. In-home mobile phone-based assessments may be more sensitive to the effects of nutritional interventions compared to traditional in-laboratory assessments.

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  28. JP Says:

    Updated 04/23/17:


    Front Neurosci. 2017 Mar 7;11:105.

    Impact of Resveratrol on Glucose Control, Hippocampal Structure and Connectivity, and Memory Performance in Patients with Mild Cognitive Impairment.

    In healthy older adults, resveratrol supplementation has been shown to improve long-term glucose control, resting-state functional connectivity (RSFC) of the hippocampus, and memory function. Here, we aimed to investigate if these beneficial effects extend to individuals at high-risk for dementia, i.e., patients with mild cognitive impairment (MCI). In a randomized, double-blind interventional study, 40 well-characterized patients with MCI (21 females; 50-80 years) completed 26 weeks of resveratrol (200 mg/d; n = 18) or placebo (1,015 mg/d olive oil; n = 22) intake. Serum levels of glucose, glycated hemoglobin A1c and insulin were determined before and after intervention. Moreover, cerebral magnetic resonance imaging (MRI) (3T) (n = 14 vs. 16) was conducted to analyze hippocampus volume, microstructure and RSFC, and neuropsychological testing was conducted to assess learning and memory (primary endpoint) at both time points. In comparison to the control group, resveratrol supplementation resulted in lower glycated hemoglobin A1c concentration with a moderate effect size (ANOVARMp = 0.059, Cohen’s d = 0.66), higher RSFC between right anterior hippocampus and right angular cortex (p < 0.001), and led to a moderate preservation of left anterior hippocampus volume (ANOVARMp = 0.061, Cohen's d = 0.68). No significant differences in memory performance emerged between groups. This proof-of-concept study indicates for the first-time that resveratrol intake may reduce glycated hemoglobin A1c, preserves hippocampus volume, and improves hippocampus RSFC in at-risk patients for dementia. Larger trials with longer intervention time should now determine if these benefits can be validated and extended to cognitive function. Be well! JP

  29. JP Says:

    Updated 12/05/17:


    J Prev Alzheimers Dis. 2017;4(1):12-15.

    Short-Term Impact of a Combined Nutraceutical on Cognitive Function, Perceived Stress and Depression in Young Elderly with Cognitive Impairment: A Pilot, Double-Blind, Randomized Clinical Trial.

    BACKGROUND: The prevalence of senile dementia is increasing worldwide, especially in the developed countries. Nevertheless, drug therapy isn’t often enough to treat this condition. Researchers are evaluating the possible impact of a preventive approach, based on an improvement of lifestyle and the intake of micronutrients. Moreover, there is an increasing interest for combined nutraceuticals that can act as memory and learning enhancers, with a significant and beneficial potential on the cognitive disorders.

    OBJECTIVE: To evaluate the effects of a rational assemblage of nutraceuticals on cognitive functions in a sample of 30 elderly subjects.

    DESIGN: Double bind, cross-over designed trial versus placebo Setting: outpatient clinical practice.

    PARTICIPANTS: 30 elderly subjects with basal Mini-Mental State Examination score between 20 and 27 and self-perceived cognitive decline.

    INTERVENTION: Treatment with a combination of nutraceuticals based on Bacopa monnieri, L-theanine, Crocus sativus, copper, folate and vitamins of B and D group. After2 months of treatment or placebo.

    MEASUREMENTS: Patients were evaluated with Mini-Mental State Examination (MMSE), Perceived Stress Questionnaire (PSQ) and Index and Self-Rating Depression Scale (SRDS).

    RESULTS: MMSE and PSQ Index significantly improved in the active treatment arm, both versus baseline and versus the parallel arm. Both groups experienced a significant improving in the SRDS scores.

    CONCLUSIONS: We obtained a good and significant improvement of the cognitive functions tested with the MMSE, PSQ-Index and SRDS score, after 2 months of combined therapy of nutraceuticals. Further confirmation will be needed to verify these observations on the middle and long term in a larger number of subjects.

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  30. JP Says:

    Updated 12/21/17:


    Am J Geriatr Psychiatry. 2017 Oct 27.

    Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial.

    OBJECTIVE: Because curcumin’s anti-inflammatory properties may protect the brain from neurodegeneration, we studied its effect on memory in non-demented adults and explored its impact on brain amyloid and tau accumulation using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile positron emission tomography (FDDNP-PET).

    METHODS: Forty subjects (age 51-84 years) were randomized to a bioavailable form of curcumin (Theracurmin® 90 mg twice daily [N = 21]) or placebo (N = 19) for 18 months. Primary outcomes were verbal (Buschke Selective Reminding Test [SRT]) and visual (Brief Visual Memory Test-Revised [BVMT-R]) memory, and attention (Trail Making A) was a secondary outcome. FDDNP-PET signals (15 curcumin, 15 placebo) were determined in amygdala, hypothalamus, medial and lateral temporal, posterior cingulate, parietal, frontal, and motor (reference) regions. Mixed effects general linear models controlling for age and education, and effect sizes (ES; Cohen’s d) were estimated.

    RESULTS: SRT Consistent Long-Term Retrieval improved with curcumin (ES = 0.63, p = 0.002) but not with placebo (ES = 0.06, p = 0.8; between-group: ES = 0.68, p = 0.05). Curcumin also improved SRT Total (ES = 0.53, p = 0.002), visual memory (BVMT-R Recall: ES = 0.50, p = 0.01; BVMT-R Delay: ES = 0.51, p = 0.006), and attention (ES = 0.96, p < 0.0001) compared with placebo (ES = 0.28, p = 0.1; between-group: ES = 0.67, p = 0.04). FDDNP binding decreased significantly in the amygdala with curcumin (ES = -0.41, p = 0.04) compared with placebo (ES = 0.08, p = 0.6; between-group: ES = 0.48, p = 0.07). In the hypothalamus, FDDNP binding did not change with curcumin (ES = -0.30, p = 0.2), but increased with placebo (ES = 0.26, p = 0.05; between-group: ES = 0.55, p = 0.02). CONCLUSIONS: Daily oral Theracurmin may lead to improved memory and attention in non-demented adults. The FDDNP-PET findings suggest that symptom benefits are associated with decreases in amyloid and tau accumulation in brain regions modulating mood and memory. Be well! JP

  31. JP Says:

    Updated 02/28/18:


    J Nutr Health Aging. 2018;22(3):446-450.

    The Effects of Green Tea Extract on Working Memory in Healthy Women.

    OBJECTIVES: This study aimed to examine the effects of green tea extract on working memory in healthy younger (21 – 29 y) and older (50 – 63 y) women.

    DESIGN: A single-blind, placebo-controlled, crossover design was used.

    SETTING: A university laboratory.

    PARTICIPANTS: Twenty non-smoking Caucasian women were recruited in the younger (10) and older (10) age group.

    INTERVENTION: Subjects received 5.4 g green tea extract (at least 45% epigallocatechin-3-gallate) or placebo (cornstarch) within a 24-hour period.

    MEASUREMENTS: Working memory was measured by reading span and N-back task paradigm. Blood sample (20 mL) was collected and measured for plasma malondialdehyde (MDA) and total antioxidant capacity (TEAC) concentration. A 24-hour recall was conducted for each treatment period to ensure similar dietary patterns.

    RESULTS: Green tea extract significantly improved reading span performance in older women, indicated by higher absolute and partial scores of reading span. No significant changes were observed in the younger group. N-back latencies and accuracies were not significantly different after green tea treatment in either age group. Plasma concentration of MDA and TEAC were not different after green tea extract in either group.

    CONCLUSION: Acute supplementation of decaffeinated green tea extract may enhance working memory capacity of women between 50 to 63 years of age. This study provides preliminary evidence that consumption of green tea extract may enhance the cognitive performance in older adults and thus provide potential chemopreventive benefits in this group. The mechanism should be explored in future research.

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  32. JP Says:

    Updated 03/05/18:


    J Alzheimers Dis. 2018 Mar 29.

    A Study of a Supplement Containing Huperzine A and Curcumin in Dementia Patients and Individuals with Mild Cognitive Impairment.

    Extracts from Huperzia serrata (HS) function as a cholinesterase inhibitor and a glutamic acid receptor antagonist. We tested a supplement containing HS extracts, curcumin, and others in dementia patients and individuals with mild cognitive impairment (MCI) in an open label study. Most patients with Alzheimer’s disease, dementia with Lewy bodies, and MCI individuals exhibited improvements in cognitive functions, as assessed by the Alzheimer’s Disease Assessment Scale-cognitive subscale Japanese version. The scores were significantly improved at 6-12 weeks compared with baseline scores (p = 0.007) and at 22-28 weeks (p = 0.004). Thus, this supplement may be administered to dementia patients as well as MCI individuals.

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  33. JP Says:

    Updated 05/28/18:


    J Neurosurg Sci. 2018 Jun;62(3):279-284.

    Pycnogenol® supplementation in minimal cognitive dysfunction.

    BACKGROUND: Impairments in cognitive function are difficult to evaluate and measure. In most cases, subjects do not perceive any alteration in their own status, particularly in case of mild cognitive impairment. In case of minimal alterations of cognitive function, no real treatment exists at the moment. Functional and/or temporary alterations in the cerebral microcirculation may be involved in cognitive impairment, and some aspects of MCI may be theoretically caused by perfusional problems. Metabolic problems and sleep disturbances can also be associated to cognitive impairment. Pycnogenol® (Horphag) is a natural compound extracted from the bark of French maritime pine, and it is a highly standardized supplement. The aim of this registry was to evaluate the effects of supplementation with Pycnogenol® over a two-month-period in otherwise healthy individuals with minimal cognitive impairment and initial cognitive dysfunction selected on the basis of their MMSE score.

    METHODS: Eighty-seven healthy subjects with a MMSE score ranging from 18 to 23 (mild impairment) were included. Their BMI was <26 kg/m2, and no metabolic disorders were present. Participants were divided into two groups: one group was treated with standard management (SM) only (N.=44), whereas the other group received Pycnogenol® supplementation (150 mg/day) in addition to SM (N.=43).

    RESULTS: In the Pycnogenol® group MMSE score at inclusion was on average 21.64±1.5; after 8 weeks of supplementation, the average MMSE score increased significantly to 25.64±1.4 (P<0.05). In controls, the initial MMSE score was 22.43±1.2, comparable to the supplement group; however, in these subjects it did not show significant improvement after 8 weeks (average after treatment: 23.00±1.3). The median increase was 18% with Pycnogenol® vs. 2.48% in the SM group (P<0.05).

    CONCLUSIONS: Pycnogenol® has shown a large number of positive effects in subjects with initial cognitive impairment, due to its effects on oxidative stress levels. The safety and tolerability of Pycnogenol® are good, and thus the supplementation regimen should be tested in larger studies with a longer follow-up.

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  34. JP Says:

    Updated 08/07/18:


    J Nutr Health Aging. 2018;22(7):837-846.

    A Combination of Essential Fatty Acids, Panax Ginseng Extract, and Green Tea Catechins Modifies Brain fMRI Signals in Healthy Older Adults.

    OBJECTIVES: To assess the effects of a combination of omega 3 essential fatty acids, green tea catechins, and ginsenosides on cognition and brain functioning in healthy older adults.

    DESIGN: Double-blind, placebo-controlled, crossover design randomized controlled trial with 26-day intervention phases and a 30-day washout period.

    SETTING: The Institute for Dementia Research and Prevention at the Pennington Biomedical Research Center.

    PARTICIPANTS: Ten independently-living, cognitively-healthy older adults (mean age: 67.3 + 2.01 years).

    INTERVENTION: Daily consumption of an investigational product (trade name “Cerbella TM”) consisting of an emulsified liquid combination of standardized fish oil, panax ginseng extract, and green tea catechins in a flavored base of lecithin phospholipids optimized to maximize bioavailability of the active ingredients.

    MEASUREMENTS: Before and after supplementation with the investigational product or placebo, participants completed cognitive tests including the Mini Mental State Exam (MMSE), Stroop test, Digit Symbol Substitution Test (DSST), and Immediate and Delayed Recall tests, as well as functional magnetic resonance imaging (fMRI) during a standard cognitive task switching paradigm.

    RESULTS: Performance on the MMSE, Stroop test, and DSST increased significantly over one month of supplementation with the investigational product (one-sample t tests, p< .05) although differences between these changes and corresponding changes during supplementation with placebo were not significant (two-sample t tests, p>.05). During supplementation with the investigational product, brain activation during task performance increased significantly more than during supplementation with placebo in brain regions known to be activated by this task (anterior and posterior cingulate cortex). Functional connectivity during task execution between task regions (middle frontal gyrus and anterior cingulate cortex) increased significantly during supplementation with the investigational product, relative to placebo. Functional connectivity during rest between task regions (precentral gyrus and middle frontal gyrus) and default mode network regions (medial frontal gyrus and precuneus) decreased during supplementation with the investigational product relative to placebo, suggesting greater segregation of task and rest related brain activity.

    CONCLUSION: One-month supplementation with a combination of omega 3 essential fatty acids, green tea catechins, and ginsenosides was associated with suggestive changes in cognitive functioning as well as modification of brain activation and brain functional connectivity in cognitively healthy older adults.

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  35. JP Says:

    Updated 09/15/18:


    Neurotherapeutics. 2018 Sep 13.

    Supranutritional Sodium Selenate Supplementation Delivers Selenium to the Central Nervous System: Results from a Randomized Controlled Pilot Trial in Alzheimer’s Disease.

    Insufficient supply of selenium to antioxidant enzymes in the brain may contribute to Alzheimer’s disease (AD) pathophysiology; therefore, oral supplementation may potentially slow neurodegeneration. We examined selenium and selenoproteins in serum and cerebrospinal fluid (CSF) from a dual-dose 24-week randomized controlled trial of sodium selenate in AD patients, to assess tolerability, and efficacy of selenate in modulating selenium concentration in the central nervous system (CNS). A pilot study of 40 AD cases was randomized to placebo, nutritional (0.32 mg sodium selenate, 3 times daily), or supranutritional (10 mg, 3 times daily) groups. We measured total selenium, selenoproteins, and inorganic selenium levels, in serum and CSF, and compared against cognitive outcomes. Supranutritional selenium supplementation was well tolerated and yielded a significant (p < 0.001) but variable (95% CI = 13.4-24.8 μg/L) increase in CSF selenium, distributed across selenoproteins and inorganic species. Reclassifying subjects as either responsive or non-responsive based on elevation in CSF selenium concentrations revealed that responsive group did not deteriorate in Mini-Mental Status Examination (MMSE) as non-responsive group (p = 0.03). Pooled analysis of all samples revealed that CSF selenium could predict change in MMSE performance (Spearman's rho = 0.403; p = 0.023). High-dose sodium selenate supplementation is well tolerated and can modulate CNS selenium concentration, although individual variation in selenium metabolism must be considered to optimize potential benefits in AD. Be well! JP

  36. JP Says:

    Updated 12/12/18:


    Eur J Nutr. 2018 Dec 10.

    A pilot dose-response study of the acute effects of haskap berry extract (Lonicera caerulea L.) on cognition, mood, and blood pressure in older adults.

    PURPOSE: Haskap (Lonicera caerulea L. or blue honeysuckle) is a plant native to the low-lying wet areas and mountains of Siberia and northeastern Asia, but is now cultivated in Canada. The dark blue berries are rich in anthocyanins, particularly cyanidin-3-O-glucoside. Previously, anthocyanin-rich fruits have been observed to benefit cognitive performance during the immediate postprandial period following a single acute dose. However, no study has currently examined the potential for haskap berries to influence cognitive performance. Here, we investigate the acute cognitive benefits of an anthocyanin-rich haskap berry extract.

    METHODS: A double-blind, counterbalanced, crossover intervention study compared the acute effects of three separate haskap berry extract doses, containing 100 mg, 200 mg, and 400 mg anthocyanins, with a sugar-matched placebo. Participants were an opportunity sample of 20 older adults, aged 62-81 years. Measures of cognition, mood, and blood pressure were recorded at baseline and 1.5 h postprandially.

    RESULTS: Compared to placebo, the 400 mg dose elicited significantly lower diastolic blood pressure and heart rate. Both 200 mg and 400 mg doses elicited significantly higher word recall, with the 400 mg dose also significantly improving word recognition scores, on an episodic memory task. However, mood, working memory and executive function task results were more equivocal.

    CONCLUSIONS: The findings provide evidence for improvements in episodic memory and blood pressure following acute supplementation with haskap berry extract, with higher doses appearing most effective. The cognitive findings concur with previous literature that suggests episodic memory effects, and not executive function effects, are most prevalent in older adults following anthocyanin-rich berry supplementation. The blood pressure outcome is consistent with a vasodilatory mechanism of action.

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