Pyridoxine supplementation does not alter in vivo kinetics of one-carbon metabolism but modifies patterns of one-carbon and tryptophan metabolites in vitamin B-6–insufficient oral contraceptive users

Rios‐Avila, Luisa; Coats, Bonnie S.; Ralat, Maria; Chi, Yueh‐Yun; Midttun, Øivind; Ueland, Per Magne; Stacpoole, Peter W.; Gregory, Jesse F.

doi:10.3945/ajcn.115.113159

Cited by 11 publications

(6 citation statements)

References 53 publications

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“…We can therefore speculate that the betaine in the drink powder has an additive effect supplementary to the action of folic acid and B vitamins in UNIMMAP. The results also suggest that the vitamin B6 in UNIMMAP is not required to reduce homocysteine in this population, supporting findings from previous trials, including those involving participants with low B6 status [20,31,32]. It appears that tailoring the drink powder design to the nutritional profile of the local population using plasma determinants of homocysteine worked well, and could be a viable approach for future supplement design.…”

Section: Discussionsupporting

confidence: 80%

A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia

et al. 2019

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Background Infant DNA methylation profiles are associated with their mother’s periconceptional nutritional status. DNA methylation relies on nutritional inputs for one-carbon metabolic pathways, including the efficient recycling of homocysteine. This randomised controlled trial in nonpregnant women in rural Gambia tests the efficacy of a novel nutritional supplement designed to improve one-carbon-related nutrient status by reducing plasma homocysteine, and assesses its potential future use in preconception trials. Methods and findings We designed a novel drink powder based on determinants of plasma homocysteine in the target population and tested it in a three-arm, randomised, controlled trial. Nonpregnant women aged between 18 and 45 from the West Kiang region of The Gambia were randomised in a 1:1:1 allocation to 12 weeks daily supplementation of either (a) a novel drink powder (4 g betaine, 800 μg folic acid, 5.2 μg vitamin B12, and 2.8 mg vitamin B2), (b) a widely used multiple micronutrient tablet (United Nations Multiple Micronutrient Preparation [UNIMMAP]) containing 15 micronutrients, or (c) no intervention. The trial was conducted between March and July 2018. Supplementation was observed daily. Fasted venepuncture samples were collected at baseline, midline (week 5), and endline (week 12) to measure plasma homocysteine. We used linear regression models to determine the difference in homocysteine between pairs of trial arms at midline and endline, adjusted for baseline homocysteine, age, and body mass index (BMI). Blood pressure and pulse were measured as secondary outcomes. Two hundred and ninety-eight eligible women were enrolled and randomised. Compliance was >97.8% for both interventions. At endline (our primary endpoint), the drink powder and UNIMMAP reduced mean plasma homocysteine by 23.6% (−29.5 to −17.1) and 15.5% (−21.2 to −9.4), respectively (both p < 0.001), compared with the controls. Compared with UNIMMAP, the drink powder reduced mean homocysteine by 8.8% (−15.8 to −1.2; p = 0.025). The effects were stronger at midline. There was no effect of either intervention on blood pressure or pulse compared with the control at endline. Self-reported adverse events (AEs) were similar in both intervention arms. There were two serious AEs reported over the trial duration, both in the drink powder arm, but judged to be unrelated to the intervention. Limitations of the study include the use of a single targeted metabolic outcome, homocysteine. Conclusions The trial confirms that dietary supplements can influence metabolic pathways that we have shown in previous studies to predict offspring DNA methylation. Both supplements reduced homocysteine effectively and remain potential candidates for future epigenetic trials in pregnancy in rural Gambia. Trial registration Clinicaltrials.gov Reference NCT03431597 .

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Section: Discussionsupporting

confidence: 80%

A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia

et al. 2019

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“…These studies confirmed the pronounced elevation of cystathionine and identified other more subtle effects on glycine, other amino acids and organic acids due to vitamin B 6 restriction. A recent study of oral contraceptive using women with chronically low plasma PLP, showed no change in plasma cystathionine concentration or its fractional synthesis rate (reflecting CBS flux) after vitamin B 6 supplementation [38, 39]. …”

Section: In Vivo Observations: Vitamin B6-dependence Of the Canonimentioning

confidence: 99%

Vitamin B6 nutritional status and cellular availability of pyridoxal 5′-phosphate govern the function of the transsulfuration pathway's canonical reactions and hydrogen sulfide production via side reactions

et al. 2016

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The transsulfuration pathway (TS) acts in sulfur amino acid metabolism by contributing to the regulation of cellular homocysteine, cysteine production, and the generation of H2S for signaling functions. Regulation of TS pathway kinetics involves stimulation of cystathionine β-synthase (CBS) by S-adenosylmethionine (SAM) and oxidants such as H2O2, and by Michaelis-Menten principles whereby substrate concentrations affect reaction rates. Although pyridoxal phosphate (PLP) serves as coenzyme for both CBS and cystathionine γ-lyase (CSE), CSE exhibits much greater loss of activity than CBS during PLP insufficiency. Thus, cellular and plasma cystathionine concentrations increase in B6 deficiency mainly due to the bottleneck caused by reduced CSE activity. Because of the increase in cystathionine, the canonical production of cysteine (homocysteine→cystathionine→cysteine) is largely maintained even during vitamin B6 deficiency. Typical whole body transsulfuration flux in humans is 3-7 μmol/h per kg body weight. The in vivo kinetics of H2S production via side reactions of CBS and CSE in humans are unknown but they have been reported for cultured HepG2 cells. In these studies, cells exhibit a pronounced reduction in H2S production capacity and rates of lanthionine and homolanthionine synthesis in deficiency. In humans, plasma concentrations of lanthionine and homolanthionine exhibit little or no mean change due to 4-wk vitamin B6 restriction, nor do they respond to pyridoxine supplementation of subjects in chronically low-vitamin B6 status. Wide individual variation in responses of the H2S biomarkers to such perturbations of human vitamin B6 status suggests that that the resulting modulation of H2S production may have physiological consequences in a subset of people.

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“…VB6’s bioavailability is constrained by complexes formed with isoniazid, cycloserine, penicillamine, and L-dopa. A subset of women who use oral contraceptives had reduced levels of pyridoxine phosphate [ 169 ]. Phenobarbital and phenytoin blood levels may drop in response to high pyridoxine doses [ 161 ].…”

Section: The Effects Of Pyridoxine/vb6 Bioavailability Dose and Effic...mentioning

confidence: 99%

B Vitamins, Glucoronolactone and the Immune System: Bioavailability, Doses and Efficiency

Munteanu,

Schwartz

2023

Nutrients

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The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a strong relationship between the recommended daily dose of selected B vitamins and a functional immune system. Regarding specific B vitamins: (1) Riboflavin is necessary for the optimization of reactive oxygen species (ROS) in the fight against bacterial infections caused by Staphylococcus aureus and Listeria monocytogenes. (2) Niacin administered within normal doses to obese rats can change the phenotype of skeletal fibers, and thereby affect muscle metabolism. This metabolic phenotype induced by niacin treatment is also confirmed by stimulation of the expression of genes involved in the metabolism of free fatty acids (FFAs) and oxidative phosphorylation at this level. (3) Vitamin B5 effects depend primarily on the dose, thus large doses can cause diarrhea or functional disorders of the digestive tract whereas normal levels are effective in wound healing, liver detoxification, and joint health support. (4) High vitamin B6 concentrations (>2000 mg per day) have been shown to exert a significant negative impact on the dorsal root ganglia. Whereas, at doses of approximately 70 ng/mL, sensory symptoms were reported in 80% of cases. (5) Chronic increases in vitamin B12 have been associated with the increased incidence of solid cancers. Additionally, glucuronolactone, whose effects are not well known, represents a controversial compound. (6) Supplementing with D-glucarates, such as glucuronolactone, may help the body’s natural defense system function better to inhibit different tumor promoters and carcinogens and their consequences. Cumulatively, the present review aims to evaluate the relationship between the selected B vitamins group, glucuronolactone, and the immune system and their associations to bioavailability, doses, and efficiency.

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Pyridoxine supplementation does not alter in vivo kinetics of one-carbon metabolism but modifies patterns of one-carbon and tryptophan metabolites in vitamin B-6–insufficient oral contraceptive users

Cited by 11 publications

References 53 publications

A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia

A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia

Vitamin B6 nutritional status and cellular availability of pyridoxal 5′-phosphate govern the function of the transsulfuration pathway's canonical reactions and hydrogen sulfide production via side reactions

B Vitamins, Glucoronolactone and the Immune System: Bioavailability, Doses and Efficiency

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