B Vitamin Supplementation Improves Overall Cognitive Functioning in Non-Aspirin Users

by | Mar 7, 2022 | 2021, Alzheimer's Disease, Brain Health, Cognitive Health, Vitamin B - General

Written by Taylor Woosley, Staff Writer. Findings suggest B-vitamin supplementation provides superior neuroprotective properties, particularly in its ability to reduce the rate of whole brain atrophy, in non-aspirin users compared to participants taking B-vitamins and aspirin.

B vitaminsDementia, a gradual progressive loss of cognitive functioning, is one of the greatest global health challenges of the 21st century. Alzheimer’s disease is the most common type of dementia, constituting about 90% of dementia cases worldwide 1. It is a neurodegenerative disorder characterized by cognitive impairment, hippocampal atrophy, neuroinflammation and intracellular neurofibrillary tangles 2.

Previous research on B vitamins suggests that deficiencies of certain B vitamins (Vitamin B6, Vitamin B12, folic acid) result in impaired methylation, synthesis and DNA repair, and may contribute to neurocognitive disorders 3. Scientific literature has long documented the prevalence of Vitamin B12 deficiency and its prevalence in the elderly population, greatly affecting the body’s role in cellular and mitochondrial metabolism 4. In addition, Vitamin B6 plays a crucial role as a co-factor in over 100 enzymatic reactions, particularly homocysteine and lipid metabolism 5. Along with Vitamin B6 and B12, folic acid functions as a coenzyme to transfer one-carbon units that are necessary for various methylation reactions, particularly for the methylation of homocysteine 6.

B Vitamins are often supplemented to improve cognitive functioning due to their effects on certain plasma amino acids called homocysteine 7. Elevated homocysteine levels, along with high levels of oxidative stress, are commonly associated with cognitive decline. Besides vitamin supplementation, aspirin is a popular medicine administered for its potential neuroprotective benefits. Aspirin acts as an anti-inflammatory and antiplatelet agent, suggesting that it could offer potential benefits to reduce neuroinflammation. Furthermore, habitual aspirin supplementation may improve cognitive health through a reduction in amyloid pathology 8.

In this retrospective analysis, data from two randomized placebo-controlled trials (the VITACOG trial and the HK trial) were compared to examine the effects of B-vitamin supplementation on cognitive functioning. The 545 participants in both the VITACOG trial (n=266) and HK trial (n=279) had mild cognitive impairment (MCI), were of similar average ages (76.8 and 77.4 respectively), subjects were randomized 1:1 to the active or placebo group, and both trials lasted 24 months. Additionally, each trial observed cognitive functioning using the CDR scale and by examining volumetric brain MRI data at baseline and two years to understand the rate of whole brain atrophy. Differences in trials pertained to dosage amounts. In the VITACOG trial subjects were given a single tablet containing 500 µg cyanocobalamin, 800 µg folic acid and vitamin B6 20 mg once per day. The HK trial administered one 500 µg methylcobalamin tablet and one 400 µg folic acid tablet once daily. The HK trial repeated the cognitive outcomes at month 12 and month 24 while the VITACOG trial repeated outcomes only at month 24. Additionally, of the participants in the VITACOG trial, 33.8% of them were aspirin users versus 22.9% of participants in the HK trial being aspirin users. Results of the comparisons of the trial groups are as follows:

  • Compared to the placebo group, B-vitamin supplementation reduced the rate of brain atrophy significantly (0.96% versus 0.73%, P=0.003).
  • When examining the interactions of aspirin, significant effects were noted in ΔCDR-global and ΔCDR-SOB (Beta = 0.993, P = 0.038, and Beta = 0.583, P = 0.009, respectively).
  • In the aspirin non-user group, as compared with the placebo group, the active group participants had significantly improved ΔCDR-global (Beta = -0.604, P = 0.019), ΔCDR-SOB (Beta = -0.223, P = 0.057) and significantly lower whole brain atrophy rate (Beta = -0.292, P = 0.001).
  • When comparing the two placebo groups, aspirin users had significantly less increase in CDR-SOB than aspirin non-users. (P = 0.019).

Study findings show the negative interaction that aspirin has on the neuroprotective potential of B vitamins. B-vitamin supplementation significantly slowed the rates of brain atrophy in participants who did not take aspirin, but no significant improvement was noted for aspirin-users. Study limitations include differences of subject characteristics when comparing the two trials, varying levels of B-vitamin supplementation between the groups, and the possibility of bias by indication is possible because aspirin use was not randomly assigned. Wu et al. suggest further research should explore the potential interactions of B-vitamins on the prevention of dementia-related disorders.

Source: Wu, Y., A. D. Smith, H. Refsum, and Timothy Kwok. “Effectiveness of B Vitamins and Their Interactions with Aspirin in Improving Cognitive Functioning in Older People with Mild Cognitive Impairment: Pooled Post-Hoc Analyses of Two Randomized Trials.” The journal of nutrition, health & aging 25, no. 10 (2021): 1154-1160.

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Posted March 7, 2022.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

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