Health Benefits of Vitamin B

HEALTH BENEFITS OF VITAMIN B

Vitamins are a group of organic compounds which are essential for normal physiological functioning but are not synthesized by the body and therefore be obtained from the diet in modest amounts. Humans require adequate 12 vitamins in total: four fat soluble vitamins (A, D, E, K) and eight water soluble vitamins, which comprise vitamin C and the seven B vitamins: thiamine (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), vitamin B6, folate (B9) and vitamin B12. The B vitamins are classified not by chemical structural similarity, but by their water solubility and the interrelated, cellular coenzyme functions that they play ^[1].

MECHANISMS OF ACTION AND FUNCTIONS OF B VITAMINS

B vitamins act as coenzymes in a substantial proportion of the enzymatic processes that support all aspects of cellular physiological function. The biologically active form of the vitamin binds to a protein “apoenzyme” to generate a “holoenzyme,” boosting the competence of the resulting enzyme in terms of the variety of processes it may catalyze. In this role, the B vitamins play key interacting roles in the majority of cellular functions. The primary bioactive form of vitamin B6, pyridoxal 51-phosphate, is an essential cofactor in the functioning of over 140 different ubiquitous enzymes required for the synthesis, degradation, and interconversion of amino acids, whereas coenzyme A (CoA), the active coenzyme form of pantothenic acid, is an obligatory cofactor for approximately 4% of all mammalian enzymes. Less often B vitamins also function as direct precursors for metabolic substrates; for example, CoA is also acetylated to form acetyl-CoA, an intermediate compound in both the generation of cellular energy and the synthesis of multiple bioactive compounds. Similarly, niacin is a precursor for ADP-ribose, which functions in multiple non-enzymatic cellular roles ^[1].

Overall, B vitamins’ variety of actions can be separated into catabolic metabolism, which results in the generation of energy, and anabolic metabolism, which results in the construction and transformation of bioactive molecules ^[1].

ROLES OF B VITAMINS

1. Thiamine (Vitamin B1)

Thiamine is a coenzyme in the pentose phosphate pathway, which is a necessary step in the synthesis of fatty acids, steroids, nucleic acids and the aromatic amino acid precursors to a range of neurotransmitters and other bioactive compounds essential for brain function. Thiamine, in addition to its activity as a cofactor in metabolic processes, plays a neuro-modulatory role in the cholinergic neurotransmitter system and contributes to the shape and function of cellular membranes, including neurons and neuroglia ^[1]. Thiamine deficiency has been linked to neurological issues such as cognitive deficiencies and encephalopathy for over a century, according to study. Both classical thiamine deficiency and Alzheimer’s disease (AD) are linked to cognitive impairments and changes in brain glucose metabolism. Research in animal has been found to suggest that supplementation with thiamine or thiamine derivatives may be able to reverse AD processes. Supplements containing thiamine derivatives have been shown to reduce plaque formation and improve memory. Research in humans has been limited, so it is not yet clear if thiamin supplementation can help this condition ^{[2, 3]}.

In addition, thiamine administration has been shown to increase end-systolic volume and New York Heart Association (NYHA) functional class in patients with heart failure. Even patients with mild to moderate heart failure have shown significant improvements in left ventricular ejection fraction (LVEF) and right ventricular area. Additionally, thiamine supplementation in heart failure patients has been shown to improve blood pressure, urine output, and functional capacity along with the LVEF improvement. As a result, thiamine supplementation may provide benefits beyond improved LVEF in heart failure patients ^[4].

2. Riboflavin (Vitamin B2)

Riboflavin, vitamin B2, is a heat-stable, water-soluble vitamin that the body uses to metabolize carbohydrates, fats, and protein into glucose for energy. This vitamin is an antioxidant that aids in the proper functioning of the immune system, as well as the maintenance of healthy skin and hair. These effects occur with the help of two coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) ^[5].

In most cellular enzymatic processes, the two flavoprotein coenzymes generated from riboflavin, FMN and FAD, are key rate limiting factors. They are crucial for the synthesis, conversion and recycling of niacin, folate and vitamin B6, and for the synthesis of all heme proteins, including hemoglobin, nitric oxide synthases, P450 enzymes, and proteins involved in electron transfer and oxygen transport and storage. Flavoproteins also have a role in the metabolism of important fatty acids in brain lipids, iron intake and use, and thyroid hormone control. Any of these processed that are dysregulated due to riboflavin deficiency would be associated with its own broad negative consequences for brain function. Riboflavin derivatives also have direct antioxidant properties and increase endogenous antioxidant status as essential cofactors in the glutathione redox cycle ^[1].

Beneficial Health Effects of Riboflavin

2.1 Antioxidant Properties

Oxidative stress is a fundamental impact of aging and degenerative disorders, as well as a functional role in the etiology of different human disease states. Antioxidant enzyme activity is greatly increased when riboflavin is supplemented. In keratoconus, riboflavin also triggers the production of a normal extracellular matrix and lowers the levels of reactive oxygen species (ROS) ^[6].

2.2 Immune System

Riboflavin enhances neutrophil and macrophage phagocytic activity and stimulates the multiplication of neutrophils and monocytes. The reduction in riboflavin concentration resulted in a decreased rate of cell proliferation. However, riboflavin administration affects neutrophil migration, inhibiting the infiltration and accumulation of activated granulocytes into peripheral sites, which may lead to a decreased inflammatory influx and, thereby, a decrease in inflammatory symptoms ^[6].

2.3 Migraine

It is still unknown how riboflavin contributes to migraine prevention. However, the reduction in oxygen metabolism caused by mitochondrial malfunction may play a role in migraine prophylaxis since an increase in riboflavin concentration may improve brain mitochondrial activities. Studies have shown that riboflavin has a good impact on migraine prophylaxis, as riboflavin is considered to play a potential role because of its features in terms of safety, toleration, and cost-effectiveness. A clinical study reported that riboflavin is an effective and low-cost prophylactic treatment in children and adolescents suffering from migraine ^[6].

2.4 Anemia

Riboflavin contributes to blood cells formation as it plays a role in erythropoiesis, enhances iron absorption and helps in the mobilization of ferritin from tissues. Riboflavin supplementation was found to improve hemoglobin concentration. Furthermore, a positive relation between riboflavin intake and anemia in women, particularly those under the age of 50, was observed ^[6].

3. Niacin (Vitamin B3)

Niacin also known as “Vitamin B3” is the generic terms for two vitamins, nicotinic acid (pyridine-3-carboxylic acid) and nicotinamide (nicotinic acid amide), which combine to form the biologically active coenzymes, nicotinamide adenine dinucleotide (NAD) and its phosphate analog, the nicotinamide adenine dinucleotide phosphate (NADP) ^[7].

Beyond energy production, these include oxidative reactions, antioxidant protection, DNA metabolism and repair, cellular signaling events (through intracellular calcium), and the conversion of folate to its tetrahydrofolate derivative. Niacin also binds agonistically at two G protein receptors, the high affinity Niacin receptor 1 (NIACR1), responsible for the skin flush associated with high intake of niacin, and the low affinity Niacin receptor 2 (NIACR2). Niacin receptors can be found in immune cells and adipose tissue, as well as throughout the brain. Modulation of inflammatory cascades and anti-atherogenic lipolysis in adipose tissue are two roles that have been established. NIACR1 receptor populations have been shown to be down-regulated in the anterior cingulate cortex of schizophrenia patients and upregulated in the substantia nigra of Parkinson’s disease patients (who have low niacin levels in general) with levels correlating with poorer sleep architecture in this group. A recent case study found that giving 250 mg of niacin to people with Parkinson’s disease reduced NIACR1 expression in peripheral immune cells and improved sleep architecture ^[1].

In vitro and in vivo studies have also shown that nicotinic acid (or activation of its molecular targets) has significant anti-inflammatory, anti-oxidant, and anti-apoptotic properties in a variety of cells and tissues, thus being potentially beneficial for the management of several pathological conditions, including type-2 diabetes, obesity, atherosclerosis, kidney and lung injury, and hyperalgesia ^[7].

4. Pantothenic Acid (Vitamin B5)

This vitamin is a substrate for the synthesis of the ubiquitous CoA. Beyond its role in oxidative metabolism, CoA contributes to the structure and function of brain cells via its involvement in the synthesis of cholesterol, amino acids, phospholipids, and fatty acids. Pantothenic acid is also involved in the synthesis of numerous neurotransmitters and steroid hormones via CoA, which is of particular importance ^[1].

Pantothenic acid deficiency has been produced experimentally and causes gastrointestinal disturbance, muscle cramps, paresthesia, ataxia, depression and hypoglycemia. It could be the cause of burning feet syndrome. Pantothenic acid deficiency occurs largely as part of a combination of severe malnutrition and vitamin deficits ^[8].

5. Pyridoxine/ Pyridoxal/ Pyridoxamine (Vitamin B6)

Vitamin B6 is a rate-limiting cofactor in the synthesis of neurotransmitters such dopamine, serotonin, γ-aminobutyric acid (GABA), noradrenaline, and the hormone melatonin, in addition to its role as a required cofactor in the folate cycle. The synthesis of these neurotransmitters is differentially sensitive to vitamin B6 levels, with even mild deficiency leading to preferential down-regulation of GABA and serotonin synthesis, resulting in the loss of GABA-mediated inhibition of neural activity, as well as disordered sleep, behavior, and cardiovascular function, as well as a loss of hypothalamus-pituitary hormone excretion control. Vitamin B6 also has a direct effect on immune function and gene transcription/expression and plays a role in brain glucose regulation. More broadly, levels of pyridoxal-51-phosphate are associated with increased functional indices and biomarkers of inflammation, and levels of pyridoxal-51-phosphate are down-regulated as a function of more severe inflammation, potentially as a consequence of pyridoxal-51-phosphate’s role either in the metabolism of tryptophan or in one-carbon metabolism. This is especially important because inflammatory processes have a role in the etiology of a variety of diseases, including dementia and cognitive decline ^[1].

6. Biotin (Vitamin B7)

The brain is particularly sensitive to the delivery and metabolism of glucose. Biotin plays a key role in glucose metabolism and homeostasis, including regulation of hepatic glucose uptake, gluconeogenesis (and lipogenesis), insulin receptor transcription and pancreatic β-cell function ^[1].

Skin rashes, hair loss, and brittle nails are all symptoms of biotin deficiency. Therefore, biotin supplements are frequently recommended for hair, skin, and nail health. However, these claims are supported, at best, by only a few case reports and small studies ^[9].

7. Folate (Vitamin B9) and Cobolamin (Vitamin B12)

Because of their complementary roles in the “folate” and “methionine” cycles, the functions of these two vitamins are intimately intertwined.  Indeed, a deficiency in vitamin B12 results in a functional folate deficiency, as folate becomes trapped in the form of methyltetrahydrofolate. An actual or functional folate deficiency, with an attendant reduction in purine/pyrimidine synthesis and genomic and non-genomic methylation reactions in brain tissue, leads to decreased DNA stability and repair and gene expression/transcription, which could hamper neuronal differentiation and repair, promote hippocampal atrophy, demyelination and compromise the integrity of membrane phospholipids impairing the propagation of action potentials. Folate-related downregulation of protein synthesis and the nucleotides required for DNA/RNA synthesis has implications for rapidly dividing tissue in particular, and thus underpins foetal developmental disorders and megaloblastic anemia (along with aspects of neuronal dysfunction) linked to either folate or vitamin B12 deficiency. The efficient functioning of the folate cycle is also necessary for the synthesis and regeneration of tetrahydrobiopterin, an essential cofactor for the enzymes that convert amino acids to both monoamine neurotransmitters (serotonin, melatonin, dopamine, noradrenaline, adrenaline), and nitric oxide ^[1].

Increased plasma homocysteine levels have been identified as a significant cardiovascular disease (CVD) risk factor.  Supplementing with folic acid and other B vitamins, which is a reasonable approach to lowering plasma homocysteine levels, could help reduce CVD risk. Several studies have demonstrated that folic acid in combination with B12 lowers homocysteine levels, although the impact of vitamin B12 alone to homocysteine reduction has not been defined ^[10].

B vitamins should be consumed as often as possible by eating a variety of healthy meals. However, some people benefit from taking a B-complex supplement. A B-complex supplement is generally safe when a person takes it as directed. However, only take very high doses of B vitamins under a doctor’s guidance.

REFERENCES

1. Kennedy DO. B Vitamins and the Brain: Mechanisms, Dose and Efficacy-A Review. Nutrients. [Internet]. 2016 [cited 2022 Mar 15]; 8: 1-29. Available form: http://www.nlm.nih.gov/pmc/articles/PMC4772032/
2. Gibson G, Hirsch J, Cirio R, Jordan B, Fonzetti P, Elder J. Abnormal thiamine-dependent processes in Alzheimer’s Disease. Lessons from diabetes. Molecular and Cellular Neuroscience. [Internet]. 2013 [cited 2022 Mar 15]; 55: 17-25. Available form: http://www.sciencedirect.com/science/article/abs/pii/S1044743112001777
3. Gibson G, Hirsch J, Fonzetti P, Jordon B, Cirio R, Elder J. Vitamin B1 (thiamine) and dementia. Annals of the New York Academy of Sciences. [Internet]. 2016 [cited 2022 Mar 15]; 1367: 21-30. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846521/
4. DiNicolantonio J, Lavie C, Niazi A, O’Keefe J, Hu T. Effects of thiamine on cardiac function in patients with systolic heart failure: systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials. The Ochsner Journal. [Internet]. 2013 [cited 2022 Mar 15]; 13: 495-9. Available form: http://www.ochsnerjournal.org/content/13/4/495.abstract
5. Mahabadi N, Bhusal A, Banks SW. Riboflavin Deficiency. StatPearls. [Internet]. 2022 [cited 2022 Mar 15]; 1-8. Available form: http://www.ncbi.nlm.nih.gov/books/NBK470460/
6. Suwannasom N, Kao I, Pruß A, Georgieva R, Bäumler H. Riboflavin: The Health Benefits of a Forgotten Natural Vitamin. International Journal of Molecular Sciences. [Internet]. 2020 [cited 2022 Mar 15]; 21: 1-22. Available form: http://www.ncbi.nih.gov/pmc/articles/PMC7037471/
7. Gasperi V, Sibilano M, Savini I, Catani MV. Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications. International Journal of Molecular Sciences. [Internet]. 2019 [cited 2022 Mar 15]; 20: 1-26. Available form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412771/
8. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Vitamin B. National Institute of Diabetes and Digestive and Kidney Diseases [Internet]. 2021 [cited 2022 Mar 15]; 1-8. Available form: http://www.ncbi.nlm.nih.gov/books/NBK548710/
9. National Institutes of Health; Office of Dietary Supplements. Biotin: Fact Sheet for Health Professionals. [cited 2022 Mar 15] Available form: http://ods.od.nih.gov/factsheets/Biotin-HealthProfessional/
10. Ryan-Harshman M, Aldoori W. Vitamin B12 and health. Canadian Family Physician. [Internet]. 2016 [cited 2022 Mar 15]; 54: 536-41. Available form: http://www.ncbi.nih.gov/pmc/articles/PMC2294088/