B Vitamins make headlines from time to time, some positive and others less so. This is a short review of the key role they play in brain and immune health.
Anxiety management
A July 22 paper in the Journal of Human Psychopharmacology: Clinical and Experimental[1]. Identified a mechanism with beneficial outcomes in the use of B6 for the reduction in anxiety, after analysing almost 500 young people over 5 years with self-reported anxiety and depression.
Such an influence can be explained because, in addition to its role as a co-enzyme in converting excitatory glutamate into inhibitory Gamma-aminobutyric acid (GABA), Vitamin B6 is involved in a number of other pathways that are likely to reduce neural excitation; it is a co-enzyme for the production of other neurotransmitters such as serotonin, dopamine, and noradrenaline; it acts as a cofactor in the kynurenine pathway in which it reduces the amount of quinolinic acid, which is an agonist to the excitatory N-methyl-D-aspartate (NMDA) receptor[2].
It is involved in the homocysteine-cysteine cycle and through this reduces levels of homocysteine, which is also an agonist of the NMDA receptor[3]. Also, via the homocysteine-cysteine cycle it provides cysteine to the glutathione cycle, which further reduces levels of the excitatory neurotransmitter glutamate by converting it to the essential antioxidant glutathione.
The doses used in this study were high relative to the RDA; for Vitamin B6 the RDA for adults aged 19–50 is 1.3 mg and the supplement used in the study contained 100 mg as pyroxidine hydrochloride.
The slowing of cognitive decline
The rate of cognitive decline in the UK population is increasing, and represents many people, with risks increasing related to age, social status, education, lifestyle and nutrition. Cases of cognitive decline in older people, where a doctor has assessed someone following concerns about memory and noted their brain function has been affected, have more than doubled over the past ten years, according to UCL researchers who published their paper in Clinical Epidemiology in March 2022[4].
A systematic review and meta analysis published the following month in April 2022 indicates that, used at the correct point in time, B vitamins can benefit cognitive function as measured by Mini-Mental State examination score changes (6155 participants; MD, 0.14, 95%CI 0.04 to 0.23), and this result was also significant in studies where placebo groups developed cognitive decline (4211 participants; MD, 0.16, 95%CI 0.05 to 0.26), suggesting that B vitamins slow cognitive decline[5].
The authors go on to state that B vitamins slow cognitive decline especially in populations who received early intervention and intervention of long duration; the study also indicates that higher intake of dietary folate, but not B12 or B6, is associated with a reduced risk of incident dementia in non-dementia aged population. Given the prevalence of dementia cases in many countries with aging populations, public health policies should be introduced to ensure that subgroups of the population at risk have an adequate B vitamin status.
Another paper out in Nutrients also in April 2022 finds evidence that in populations with a B12 deficiency, that cognitive impairment was improved when supplemented with B12[6]. Whilst the authors are cautious of making too strong an association, the multitude of studies on the role of B vitamins in mild cognitive prevention tend to favour their use, and even more so if a particular deficiency is identified.
To understand more about the relational interactions of the B vitamins as a group (thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), vitamin B6, biotin (B7), folate (B9) and vitamin B12 ), rather than as individual forms, the Nutrients Review Paper published in 2016 presents a constructive explanation[7].
Immune support
Dietary B vitamins are supplied by plants and animal products in ample quantities (but with varying bioavailability and concentration[8]), although a variety of conditions can increase the demand and cause deficiencies in B vitamins. Malnutrition, which remains a prevalent problem in developed and developing countries world-wide, exercise, stress, drug abuse, alcohol consumption and pregnancy also increase cellular demands for B vitamins. Notably, vitamin B12 is not produced by plants, placing vegans and vegetarians solely reliant on microbial sources, thereby placing them at risk for B12 deficiency in the absence of supplementation.
B group vitamins represent essential micronutrients for myriad metabolic and regulatory processes required for human health, serving as cofactors used by hundreds of enzymes that carry out essential functions such as energy metabolism, DNA and protein synthesis, immune management and other critical functions. One of the intersecting roles recognised to be a risk factor for mental wellbeing generated by B vitamin deficiency is the induction and proliferation of low molecular weight inflammatory cytokines[9].
There is a need to highlight the importance of B vitamins because they play a pivotal role in cell functioning, energy metabolism, and proper immune function. B vitamins assist in proper activation of both the innate and adaptive immune responses, reduce pro-inflammatory cytokine levels, improve respiratory function, maintain endothelial integrity, prevent hypercoagulability and can reduce the length of stay in hospital[10]. With the recent proliferation of Sars-Cov-2 and subsequent variants, it may be useful to consider that optimal vitamin B status may confer a valued benefit to immunological response and related immune memory[11],[12].
What does this mean
Deficiency states of certain B vitamins (B12 in particular) increase in frequency with age but can occur at any age depending on many modifiable factors[13]. The use of an oral supplementation of B vitamins provides a clinically relevant input, where sub clinical and clinical deficiency exists[14],[15].
There are multiple interactions between the eight B vitamin forms, and collective ingestion via supplementation, or enhanced ingestion through appropriate food selection are well recognised to assist with optimisation of need.
Fruits, vegetables, and whole grains are still among the healthiest foods on the planet, but consumers may not be getting the nutrients they’re counting on from plant-based foods because of increased atmospheric carbon dioxide and intensive farming practices. And if these nutrient declines continue, some people may be at elevated risk for developing deficiencies in certain nutrients or less able to protect themselves from chronic diseases through good nutrition[16].
In the absence of an optimal diet, administration of the entire B vitamin group, at doses in excess of the minimums recommended to avoid deficiency is a rational approach for preserving brain function, immune competence and health.
References
[1] Field, D. T., Cracknell, R. O., Eastwood, J. R., Scarfe, P., Williams, C. M., Zheng, Y., & Tavassoli, T. (2022). High-dose Vitamin B6 supplementation reduces anxiety and strengthens visual surround suppression. Human Psychopharmacology: Clinical and Experimental, e2852.
[2] Curto M, Lionetto L, Negro A, Capi M, Fazio F, Giamberardino MA, Simmaco M, Nicoletti F, Martelletti P. Altered kynurenine pathway metabolites in serum of chronic migraine patients. J Headache Pain. 2015;17:47.
[3] Deep SN, Mitra S, Rajagopal S, Paul S, Poddar R. GluN2A-NMDA receptor-mediated sustained Ca2+ influx leads to homocysteine-induced neuronal cell death. J Biol Chem. 2019 Jul 19;294(29):11154-11165.
[4] Hallam B, Petersen I, Cooper C, Avgerinou C, Walters K. Time Trends in Incidence of Reported Memory Concerns and Cognitive Decline: A Cohort Study in UK Primary Care. Clin Epidemiol. 2022;14:395-408
[5] Zhibin Wang, Wei Zhu, Yi Xing, Jianping Jia, Yi Tang, B vitamins and prevention of cognitive decline and incident dementia: a systematic review and meta-analysis, Nutrition Reviews, Volume 80, Issue 4, April 2022, Pages 931–949
[6] Ueno A, Hamano T, Enomoto S, Shirafuji N, Nagata M, Kimura H, Ikawa M, Yamamura O, Yamanaka D, Ito T, Kimura Y, Kuriyama M, Nakamoto Y. Influences of Vitamin B12 Supplementation on Cognition and Homocysteine in Patients with Vitamin B12 Deficiency and Cognitive Impairment. Nutrients. 2022 Apr 2;14(7):1494.
[7] Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy–A Review. Nutrients. 2016 Jan 27;8(2):68.
[8] Fruits and vegetables are less nutritious than they used to be. National Geographic May 3, 2022
[9] Mikkelsen K, Stojanovska L, Prakash M, Apostolopoulos V. The effects of vitamin B on the immune/cytokine network and their involvement in depression. Maturitas. 2017 Feb;96:58-71.
[10] Nutrition and Immunity (Book)
[11] Shakoor H, Feehan J, Mikkelsen K, Al Dhaheri AS, Ali HI, Platat C, Ismail LC, Stojanovska L, Apostolopoulos V. Be well: A potential role for vitamin B in COVID-19. Maturitas. 2021 Feb;144:108-111.
[12] Sette A, Crotty S. Immunological memory to SARS-CoV-2 infection and COVID-19 vaccines. Immunol Rev. 2022 Jun 22.
[13] McLean E, de Benoist B, Allen LH. Review of the magnitude of folate and vitamin B12 deficiencies worldwide. Food Nutr Bull. 2008 Jun;29(2 Suppl):S38-51.
[14] Vincenti A, Bertuzzo L, Limitone A, D’Antona G, Cena H. Perspective: Practical Approach to Preventing Subclinical B12 Deficiency in Elderly Population. Nutrients. 2021 Jun 2;13(6):1913..
[15] Hunt A, Harrington D, Robinson S. Vitamin B12 deficiency. BMJ. 2014 Sep 4;349:g5226.
[16] Helena Bottemiller Evich. Politico – The Great Nutrient Collapse 13.9.2017 (Agenda 2020)
