Methylation & B-Complex — References

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Parent Topic: Methylation & B-Complex | References Hub: 02 - Compounds & Molecules References MOC

Landmark Peer-Reviewed Studies

Citation: Smith, A. D., Smith, S. M., de Jager, C. A., Whitbread, P., Johnston, C., Agacinski, G., Oulhaj, A., Bradley, K. M., Jacoby, R., & Refsum, H. (2010). Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS ONE, 5(9), e12244.
Identifiers: PMID: 20838622 (PubMed · Europe PMC) | DOI: 10.1371/journal.pone.0012244 (DOI · SciDB · Scholar)
Study Design & Sample Size: 24-month randomized, double-blind, placebo-controlled trial using serial volumetric cranial MRI in elderly subjects ( $\geq 70 years$ ) with Mild Cognitive Impairment ( $N = 168$ completed MRI).
Key Quantitative Outcomes: Daily high-dose B-vitamin therapy ( $800 μ g$ folate, $500 μ g$ vitamin B12, $20 mg$ vitamin B6) lowered plasma total homocysteine by $- 22.5%$ (vs. $+ 7.7%$ in placebo) and reduced the overall rate of whole-brain atrophy by $- 29.6%$ ( $0.76%/ year$ vs. $1.08%/ year$ , $p = 0.001$ ). In subjects in the top quartile of baseline homocysteine ( $> 13.0 μ mol/L$ ), brain atrophy rate was reduced by $- 53.3%$ ( $p = 0.001$ ).

Citation: Douaud, G., Refsum, H., de Jager, C. A., Jacoby, R., Nichols, T. E., Smith, S. M., & Smith, A. D. (2013). Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proceedings of the National Academy of Sciences, 110(23), 9523–9528.
Identifiers: PMID: 23690582 (PubMed · Europe PMC) | DOI: 10.1073/pnas.1301816110 (DOI · SciDB · Scholar)
Study Design & Sample Size: Voxel-based morphometry neuroimaging sub-analysis of the 2-year VITACOG RCT ( $N = 156$ ).
Key Quantitative Outcomes: In specific Alzheimer’s disease-vulnerable gray matter regions (bilateral hippocampus, parahippocampal gyrus, inferior parietal lobule, and retrosplenial cortex) among subjects with elevated baseline homocysteine ( $> 11.06 μ mol/L$ ), B-vitamin supplementation reduced gray matter atrophy by 7-fold ( $- 0.54%$ vs. $- 3.71%$ over 2 years, $p < 0.01$ ).

Citation: Horigan, G., McNulty, H., Ward, M., Strain, J. J., Purvis, J., & Scott, J. M. (2010). Riboflavin lowers blood pressure in cardiovascular disease patients homozygous for the 677C→T polymorphism in MTHFR. Journal of Hypertension, 28(3), 478–486.
Identifiers: PMID: 20090552 (PubMed · Europe PMC) | DOI: 10.1097/HJH.0b013e328334c126 (DOI · SciDB · Scholar)
Study Design & Sample Size: 16-week randomized, double-blind, placebo-controlled trial in premature CVD patients stratified by MTHFR C677T genotype ( $N = 197$ , including $n = 49$ homozygous TT).
Key Quantitative Outcomes: Supplementation with $1.6 mg/day$ riboflavin (FAD precursor) selectively lowered systolic blood pressure by $- 9.2 mmHg$ ( $p = 0.001$ ) and diastolic blood pressure by $- 6.0 mmHg$ ( $p = 0.003$ ) in MTHFR 677TT homozygotes—matching or exceeding single antihypertensive drug efficacy—with no blood pressure shift in CC or CT genotypes.

Citation: Vrolijk, M. F., Opperhuizen, A., Jansen, E. H., Hageman, G. J., Bast, A., & Haenen, G. R. (2017). The vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function. Toxicology in Vitro, 44, 206–212.
Identifiers: PMID: 28716455 (PubMed · Europe PMC) | DOI: 10.1016/j.tiv.2017.07.009 (DOI · SciDB · Scholar)
Study Design & Sample Size: Mechanistic human neuroblastoma (SH-SY5Y) and enzymatic kinetic investigation of vitamin B6 vitamers (pyridoxine, pyridoxal, pyridoxamine, and pyridoxal-5’-phosphate).
Key Quantitative Outcomes: Demonstrated that unmetabolized pyridoxine (PN) competitively inhibits pyridoxal-5’-phosphate (P5P)-dependent enzymes (including tyrosine decarboxylase and alanine transaminase, $p < 0.01$ ) and induces pro-apoptotic gene expression (Bax/Caspase-8), whereas active pyridoxal-5’-phosphate (P5P) exhibited no enzymatic inhibition or neurotoxicity.