Micronutrient Supplementation and Ergogenesis — Vitamins
Luke Bucci in Nutrients as Ergogenic Aids for Sports and Exercise, 2020
Vitamin B12 (cyanocobalamin) supplementation to boys or normal young men did not change half-mile run times,218 grip strength, heart rate recovery, maximal cycle ergometer times,219 VO2max, and other standard strength tests.220 Evidence for a subjective “tonic” effect on patients complaining of “tiredness” was found for hydroxocobalamin (B12) injections in a double-blind crossover study.221 Relation of these finding to athletes may explain the popularity of B12 injections and B12 supplements. Currently, the primary, coenzymatic form of B12, known as cobamamide, Dibencozide™ or 5,6-dimethyl-benzimidazolyl cobamide coenzyme222 has become a popular supplement among weightlifters.223,224 Promotional literature contains a favorable comparison of cobamamide with anabolic steroids as an anabolic agent. What is not generally explained is that the study referred to was performed with 35 young children with growth deficiencies, osteoporosis, or hypoproteinemia.225 Other supporting evidence of B12 as an “anabolic agent” is found in European pharmacopeias, but no studies on athletes are found.
Methylmalonic acidemia
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Genetic heterogeneity was evident early in the demonstration, in that some patients with methylmalonic acidemia were responsive to large doses of vitamin B12, while others were not [4]. The methylmalonyl CoA mutase enzyme has a vitamin B12-derived cofactor, adenosylcobalamin (AdoCbl). Patients who are B12-responsive clinically have defects in the synthesis of the cofactor. Unresponsive patients have defects in the apoenzyme itself. Complementation studies have indicated the presence of distinct groups (Figure 3.1). Those with apoenzyme defects have been designated mut− or mut0 depending on whether they have little or no residual mutase activity. Groups A and B represent defects in AdoCbl synthesis. A differential diagnosis of methylmalonic acidemia is shown in Table 3.1.
Vitamin B12
Judy A. Driskell, Ira Wolinsky in Sports Nutrition, 2005
Cobalamins are critical for cell growth and division, by acting as coenzymes in two reactions, methylcobalamin in methionine synthase and adenosylcobalamin in methyl malonyl CoA mutase. The former reaction involves the remethylation of homocysteine using 5-methyltetrahydrofolate as methyl donor. Through this reaction, vitamin B12 is linked with the folate system.2 In the absence of B12, the methyl group cannot be transferred from the folate, leading to increased levels of 5-methyltetrahydrofolate. The latter cannot be converted to tetrahydrofolate by reversal of its formation, so the folate pool becomes “trapped” in the methyl form. Then tetrahydrofolate is not available to transfer one-carbon groups, especially in the thymidylate synthetase reaction, which leads to diminished DNA synthesis. Rapidly proliferating tissues such as the hematopoietic system, the gastrointestinal epithelium and the developing fetus have the greatest requirement for DNA synthesis and are therefore the major tissues affected in clinical cobalamin deficiency. Recently, vitamin B12 deficiency has been linked with an elevation in plasma homocysteine concentration, which has been recognized as an important risk factor for the development of atherosclerosis.3 The second reaction, i.e., methyl malonyl mutase, converts methyl malonyl CoA to succinyl CoA and is involved in metabolism of propionate groups generated in fatty acid oxidation.
Evaluation of transcobalamin II rs1801198 and transcobalamin II receptor rs2336573 gene polymorphisms in recurrent spontaneous abortion
Published in Journal of Obstetrics and Gynaecology, 2018
Mohammad Hashemi, Mojgan Mokhtari, Vajiheh Yazdani-Shahrbabaki, Hiva Danesh, Fatemeh Bizhani, Mohsen Taheri
Vitamin B12 (cobalamin) is an essential nutrient for humans because its derivatives, methylcobalamin and adenosylcobalamin, serve as coenzymes in two important enzymatic reactions; methionine synthase and methylmalonyl-CoA mutase (Castro et al. 2006; Depeint et al. 2006). Vitamin B12 deficiency was found to be an important risk factor for RSA (Reznikoff-Etievant et al. 2002; Hubner et al. 2008; Puri et al. 2013). The most important Vitamin B12 transport protein in the plasma is transcobalamin II (TCN2) which is synthesised mainly in the liver with a molecular weight of approximately 43 kDa (Seetharam and Li 2000). TCN2 gene has been mapped to chromosome 22, between bands 22q12 and 22q13 (Li et al. 1995) spans 20 kb, contains nine exons and eight introns, and shows a substantial heterogeneity (Li et al. 1993, 1995; Namour et al. 1998).
Hyperhomocysteinemia: a trigger for complement-mediated TMA?
Published in Acta Clinica Belgica, 2021
J Bernards, P Doubel, G Meeus, E Lerut, A Corveleyn, L P Van Den Heuvel, W Meersseman, D K Kuypers, KJ Claes
Cobalamin C (cblC) deficiency, another cause of thrombotic microangiopathy, is a rare metabolic disorder characterized by a functional vitamin B12 deficiency. The disease is caused by a compound heterozygous or homozygous mutations in the gene encoding for Methyl Malonic Aciduria and Homocystinuria type C (MMACHC) protein. The defective cblC blocks an important step in the conversion of cyanocobalamin to two essential cofactors: adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). MeCbl is a cofactor required for the conversion of homocysteine to methionine. AdoCbl is a cofactor required for the conversion of methylmalonyl-CoA to Succinyl-CoA. Consequently, cblC disease leads to methionine deficiency together with marked elevations in plasma homocysteine and methylmalonic aciduria. The disease has a broad range of phenotypic features with manifestations at an early age including neurocognitive symptoms, failure to thrive, ocular, cardiovascular and renal disease but also arterial hypertension and TMA presenting at a later age. Treatment consists of hydroxycobalamin, betaine and folinic acid [1,3,4].
Does vitamin B12 deficiency explain psychiatric symptoms in recreational nitrous oxide users? A narrative review
Published in Clinical Toxicology, 2021
Michelle C. Paulus, Anjali M. Wijnhoven, Gerdinique C. Maessen, Shannon R. Blankensteijn, Marcel A. G. van der Heyden
Vitamin B12, otherwise known as cobalamin, is characterized by a central cobalt ion surrounded by a corrin ring. Depending on the residual group bonded to the central cobalt ion, cobalamin is referred to as methyl-, adenosyl-, hydroxo- and cyanocobalamin. Nitrous oxide irreversibly inactivates vitamin B12 in vivo by oxidizing the cobalt ion from its Co1+ valent form to a Co2+ valent form [43], transforming it from the monovalent to the divalent state [44]. Cobalamin has an important metabolic role in two pathways, through two of its chemical forms adenosylcobalamin and methylcobalamin (Figure 3). In the mitochondria, adenosylcobalamin serves as cofactor for methylmalonyl coenzyme A mutase, to convert methylmalonyl-coenzyme A into succinyl-coenzyme A. Without the presence of the cofactor adenosylcobalamin, methylmalonyl-coenzyme A will be converted into methylmalonic acid (MMA). In the cytosol, methylcobalamin serves as a cofactor for methionine synthase, to convert homocysteine to methionine [44]. Methionine synthase is a cytosolic enzyme that plays a crucial role in the formation of methyl groups for the synthesis of DNA, RNA, and catecholamines [43]. Furthermore, methionine synthase is essential for methylation of the myelin sheath phospholipids [45]. Deficiency of methylcobalamin can lead to decreased activity of methionine synthase and thus decreased DNA formation and demyelination. Cobalamin deficiency is accompanied with the elevation of MMA and homocysteine due to reduced metabolism in both pathways. Accumulation of homocysteine is closely related to vascular endothelial injury and thrombosis [46], and accumulation of MMA leads to demyelination of neurons [47]. Both of these processes could contribute to the development of psychiatric disorders.
Related Knowledge Centers
- Active Site
- Carotenoid
- Cofactor
- Enzyme
- Hydroxocobalamin
- Methylcobalamin
- Vitamin B12
- Cyanocobalamin
- Deoxyadenosyl Radical
- Methylmalonyl-Coa Mutase