Folate, vitamin B2, vitamin B6 and vitamin B12 for memory

B Vitamins Calm the Seas of Memory
By increasing cognitive function across a wide range of activities

By Will Block

A decline in cognitive functions occurs as part of what many conventional thinkers refer to as “normal aging.” But this — as readers of Life Enhancement know — is not inevitable and therefore not “normal.” The failure to solve this problem is why dementias such as Alzheimer’s are like rogue waves that suddenly rise up in the ocean to capsize and overwhelm anything in their paths. However, just as the Queen Mary ocean liner with 16,082 troops onboard in December of 1942 survived the broadside of a 92-foot wave,1 so can we survive the waves that attack our brains — through the use of the right supplements, to calm the seas of our memory functions.


Low levels of B vitamins
have been associated with increased
homocysteine, an amino acid
known to have a direct neurotoxic
effect in the brain where it is thought
to potentiate beta-amyloid
neurotoxicity, and thus exacerbate
Alzheimer’s disease.


Improving Cognitive Functions

Scientists have reported for many years that numerous aspects of cognitive impairment can be improved through changing health behavior, and especially through nutritional supplementation. Undeniably, certain B vitamins — including folate, vitamin B2 (riboflavin), vitamin B6 (pyridoxine), and vitamin B12 (cyanocobalamin) — have been investigated in many clinical trials, and found to improve cognitive functions.


South Korea has one of the most
rapidly aging populations
in the world.


Homocysteine and Beta-Amyloid Neurotoxicity

Figure 1. Methylation involves the B vitamins folate, vitamin B2 (riboflavin), vitamin B6 (pyridoxine), and vitamin B12 (cyanocobalamin).
LEM1502Methylation2740.gif
(click on thumbnail for full sized image)

These B vitamins are involved in one-carbon transfer reactions such as methylation (see Fig. 1), which is necessary for the production of monoamine neurotransmitters, phospholipids, and nucleotides in the brain. Without a sufficient supply of these molecules, memory would be dysfunctional. Furthermore, low levels of these B vitamins have been associated with increased homocysteine, an amino acid known to have a direct neurotoxic effect in the brain where it is thought to potentiate beta-amyloid neurotoxicity, and thus exacerbate Alzheimer’s disease (AD).2 Several cross-sectional and longitudinal studies have suggested that elevated homocysteine levels may be an independent risk factor for impaired cognitive function or AD.

Looking at Rapidly Aging Population

A new study, noting that no study had been conducted on relationships between B vitamin intake and cognitive function among the elderly in Korea, was designed to examine this correlation.3 What makes this especially interesting is that South Korea has one of the most rapidly aging populations in the world. A recent Health Ministry report estimated that 9.2% of elderly aged ≥ 65 years have dementia and 27.8% have mild cognitive impairment (MCI).


Higher levels of B2, B6, B12, and
folate, tend to lower the levels of
neurotoxic homocysteine.


Three hundred twenty-one subjects were selected and divided into groups based on their memory failings: 100 with MCI; 100 with AD; and 121 with no discernable memory problems.

Nutrient Intake via 24-Hour Recall

Figure 2. The Boston Naming test is a widely used neuropsychological assessment tool to measure confrontational word retrieval in individuals with aphasia or other language disturbance caused by stroke, Alzheimer’s disease, or other dementing disorder. A common and debilitating feature is anomic aphasia, impairment in the ability to name objects.
LEM1502BostonNaming2740.gif
(click on thumbnail for full sized image)

Dietary intake data were obtained using a 24-hour recall method, and plasma folate and vitamin B12 concentrations were analyzed by radioimmunoassay. Also, homocysteine was assessed by a high performance liquid chromatography-fluorescence method.

Information on brand names and consumption frequency was collected from subjects ingesting dietary supplements. Daily nutrient intake from dietary supplements was calculated using frequency and nutrient content of supplements. Dietary folate equivalent was calculated and folate and other B vitamin intake data, including supplements, were compared with estimated average requirements of Korean Dietary Reference Intakes.

Confounding Considered

Possible confounding factors were considered on the association between B vitamin intake and cognitive function. A correlation test was used to analyze associations between nutrient intake and plasma folate, vitamin B12 and homocysteine levels by group.

B Vitamin Intake Correlated with Lower Homocysteine Level

The researchers found that plasma levels of folate and vitamin B12 were positively correlated with B vitamin intake. Plasma homocysteine was negatively correlated with total intake of vitamins B2, B6, B12 and folate. This means that the more taken of any or all of the B vitamins considered, the lower the levels of neurotoxic homocysteine.

Vitamins B2, B6, and B12 Raise Memory Scores in AD Group

Figure 3. Verbal fluency tests are a kind of psychological test in which participants have to say as many words as possible from a category in a given time (usually 60 seconds).
LEM1502verbalfluency274.gif
(click on thumbnail for full sized image)

In the AD group, a multiple regression analysis after adjusting for covariates revealed positive relationships between vitamin B2 intake and test scores for the MMSE-KC, Boston Naming (see Fig. 2), Verbal Fluency (see Fig. 3), Word List Memory and Constructional Recall Tests. In the AD subjects, no association was found between cognitive function scores and any dietary parameters.

Also, in the AD group, positive correspondences were also found between vitamin B6 intake and all of the same memory tests for vitamin B2, plus Word List Recognition.

Affirmative associations were also observed between vitamin B12 intake and MMSE-KC, Boston Naming, Constructional Recall Tests, and Constructional Praxis.

Vitamins B2, B6, and Folate Raise Memory Scores in MCI Group

In the MCI group, vitamin B2 intake was positively associated with the MMSE-KC and Boston Naming Test. Vitamin B6 intake was positively associated with the MMSE-KC test. And folate intake was positively associated with the MMSE-KC and Word List Memory test. There were no positive associations between Vitamin B12 and any of the tests for MCI subjects. No associations were observed in the normal group. Considering all the test results, total B vitamin intake is associated with cognitive function in cognitively impaired AD and MCI elderly, and the association is stronger in AD patients (see Table 1).


In the AD subjects, no association
was found between cognitive function
scores and any dietary parameters.


Importantly, plasma levels of folate and vitamin B12 were positively correlated with B vitamin intake, while plasma homocysteine was negatively correlated with total intake of vitamins B2, B6, B12 and folate.

Table 1. Associations between total intakes of B vitamins and positive test results.
LEM1502Associations274.gif
(click on thumbnail for full sized image)

Summarily, in the AD group, positive relationships were found between B vitamin intake and all memory tests, except Word List Recall.

These results suggested that total B vitamin intake is associated with cognitive function in cognitively impaired AD and MCI elderly, and the association is stronger in AD patients.

Homocysteine Negatively Corresponds to Memory

A leading conclusion of the study is that dietary and total B vitamin intake was negatively correlated with plasma homocysteine levels and positively associated with cognitive function scores, with different associations according to cognitive status.


Total B vitamin intake is
associated with cognitive function in
cognitively impaired AD and MCI
elderly, and the association
is stronger in AD patients.


To recap, positive associations between total B vitamin intake and cognitive function were observed for all of the B vitamins — vitamins B2, B6, B12 and folic acid in the AD group — and for vitamins B2, B6 and folate in the MCI group.

No association was observed between vitamin B intake and cognitive function in the normal group. The results were similar to a previous finding by the same researchers5 that plasma folate, vitamin B12, and homocysteine are associated with cognitive function in cognitively impaired (AD and MCI) elderly, with a stronger association in those with AD. The results indicated that plasma folate and vitamin B12 were associated with homocysteine and cognitive function, which was also reported in other prior studies,6–8 where dietary intake of homocysteine-lowering vitamins B2, B6, B12 and folate were also related.

Prior Support for Negative Correlation

Figure 4. Homocysteine is a byproduct of methionine, which is formed from the S-adenylmethionine during methylation of biomolecules and hydrolysis of S-adenosylhomocysteine to homocysteine.
LEM1502Homocysteine274.gif
(click on thumbnail for full sized image)

The negative correlation between plasma homocysteine and B vitamin intake among the elderly is also supported by previous reports.9 Since vitamins B2, B6, B12 and folate are metabolically interrelated in one-carbon metabolism (see Fig. 1), it is not unexpected that the intake of vitamins B2, B6, B12 and folate is inversely related to plasma homocysteine. Homocysteine is a by-product of a sulfur-containing amino acid methionine, which is formed from the universal methyl donor S-adenosyl methionine (see Fig. 4). The resulting homocysteine is remethylated to methionine by methylenetetrahydrofolate, generated in the one-carbon metabolism cycle where homocysteine-lowering B vitamins are metabolically interrelated.

How Much Supplemental B Vitamins Should Be Taken?

In the current study, cognitive function test scores were positively associated with intake of vitamins B2, B6, B12 and folate in the AD group; vitamins B2, B6 and folate in the MCI group; and none in the normal group. To the best of the researchers’ knowledge, no study had previously investigated an association between B vitamin intake and cognitive function in AD patients. Intervention studies reported that B vitamin supplementation [Folic acid (5 mg/day) and B12 (1 mg/day)] could improve cognitive performance, but only in mild to moderately demented AD patients who started with elevated homocysteine levels (baseline).10,11


To the best of the
researchers’ knowledge, no study
had previously investigated an
association between B vitamin intake
and cognitive function in AD patients.


The Alzheimer Disease Cooperative Study12 reported that in mild AD treatment with high-dose B vitamin supplements [Folic acid (5 mg/day), B6 (25 mg/day) and B12 (1 mg/day)] slowed cognitive decline, whereas in moderate AD it did not.

Once again, in the current Korean study’s MCI group, intake of vitamins B2, B6 and folate was positively associated with cognitive function test scores. This is also a new finding, indicating that B vitamins improve cognitive function in MCI patients. In an intervention study on MCI subjects, researchers reported that B vitamin supplementation [folic acid (0.8 mg/day), B12 (0.5 mg/day), B6 (20 mg/day)] stabilized executive function and improved global cognition, episodic and semantic memory, and global clinical dementia rating scores in patients with elevated homocysteine levels at baseline.13


In Korea, two studies reported
a positive relationship between
vitamin B2 intake and cognitive
function scores in normal Korean
elderly subjects.


Cognitive Gain Not Found in the Normal Group

In the normal group of the Korean study, no association was observed between B vitamin intake and cognitive function. Despite some conflicts in this regard with prior studies, a recent study out of the UK14 reported no association between B vitamin intake and cognitive function scores in normal elderly patients. However, in Korea, two studies reported a positive relationship between vitamin B2 intake and cognitive function scores including MMSE-K in normal Korean elderly subjects.15,16 Also, other studies have demonstrated that supplementation with folic acid, B12, and B6 improve cognitive function such as immediate and delayed memory, information processing speed, and sensorimotor speed.17–19

In the Absence of Continued Supplementation

To repeat, despite the limitations of an observational study, to the best of the researchers’ knowledge, this is the first study investigating the relationship between cognitive function scores and dietary intake by cognitive status. The association between B vitamin intake and cognitive function was stronger in cognitively impaired AD and MCI patients than in normal elderly in Korea. This does not mean that supplementation with B vitamins is unnecessary, even if you are not yet among the elderly, nor yet experiencing measureable mild cognitive impairment, nor in the throes of Alzheimer’s. Many studies have shown benefits that, in the absence of continued supplementation, may dissipate and lead to age-related cognitive decline.

References

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  3. Kim H, Kim G, Jang W, Kim SY, Chang N. Association between intake of B vitamins and cognitive function in elderly Koreans with cognitive impairment. Nutr J. 2014 Dec 17;13(1):118.
  4. Korean Ministry of Health and Welfare: The Korean National Health Nutrition Examination Survey 2011. Seoul: Korean Ministry of Health and Welfare; 2012.
  5. Kim G, Kim H, Kim KN, Son JI, Kim SY, Tamura T, Chang N: Relationship of cognitive function with B vitamin status, homocysteine, and tissue factor pathway inhibitor in cognitively impaired elderly: a cross-sectional survey. J Alzheimers Dis. 2013;33:853 – 62.
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  8. Riggs KM, Spiro A 3rd, Tucker K, Rush D: Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the NormativeAging Study. Am J Clin Nutr. 1996;63:306 – 314.
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  12. Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF, Bottiglieri T, Jin S, Stokes KT, Thomas RG, Thal LJ; Alzheimer Disease Cooperative Study. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008 Oct 15;300(15):1774 – 83.
  13. de Jager C, Oulhaj A, Jacoby R, Refsum H, Smith AD: Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int J Geriatr Psychiatry. 2012;27:592 – 600.
  14. McNeill G, Jia X, Whalley LJ, Fox HC, Corley J, Gow AJ, Brett CE, Starr JM, Deary IJ: Antioxidant and B vitamin intake in relation to cognitive function in later life in the Lothian Birth Cohort 1936. Eur J Clin Nutr. 2011;65:619 – 26.
  15. Lee L, Kang SA, Lee HO, Lee BH, Park JS, Kim JH, Jung IK, Park YJ, Lee JE: Relationships between dietary intake and cognitive function level in Korean elderly people. Public Health. 2001;115:133 – 8.
  16. Kim JH, Kang SA, Ahn HS, Jung IK: Relationship between cognitive function and dietary patterns in Korean elderly women. J Nutr Health. 1998;31:1457 – 67.
  17. Bryan J, Calvaresi E, Hughes D: Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages. J Nutr. 2002;132:1345 – 56.
  18. Durga J, van Boxtel M, Schouten E, Kok F, Jolles J, Katan M: Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial. Lancet. 2007;369:208 – 16.
  19. Walker JG, Batterham PJ, Mackinnon AJ, Jorm AF, Hickie I, Fenech M, Kljakovic M, Crisp D, Christensen H: Oral folic acid and vitamin B12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms-the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr. 2012;95:194 – 203.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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