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Vitamin B6 (Pyridoxine)

Vitamins

Overview

Vitamin B6, chemically known as pyridoxine, is a water-soluble B-vitamin that functions primarily as a co-enzyme in more than 100 enzymatic reactions. Its most critical role is as a co-factor for enzymes involved in amino-acid metabolism, neurotransmitter synthesis, and the regulation of homocysteine, thereby influencing both metabolic and neurological health.

Benefits

  • Neuro-cognitive support: Adequate pyridoxine improves synthesis of serotonin, dopamine, and GABA, which correlates with improved mood, reduced depressive symptoms, and better cognitive performance in older adults (e.g., J. Nutr. 2020).
  • Metabolic & cardiovascular health: As a co-factor for cystathionine β-synthase, it lowers plasma homocysteine, a risk factor for cardiovascular disease (J. Clin. Endocrinol. 2019).
  • Hemoglobin formation: Essential for the conversion of aminolevulinic acid to porphobilinogen, supporting heme synthesis and preventing anemia.
  • Immune modulation: Enhances lymphocyte proliferation and cytokine production, improving vaccine response and reducing infection duration (Clin. Immunol. 2021).
  • Pregnancy outcomes: Adequate intake reduces risk of preeclampsia and improves fetal brain development (Maternal-Fetal Med. 2022).
  • Nausea & vomiting in pregnancy: High-dose pyridoxine (10–25 mg) combined with doxylamine is an evidence-based treatment for hyper-emesis gravidarum.

How It Works

  • Process: Pyridoxine is converted intracellularly to pyridoxal-5′-phosphate (PL-5′P), the biologically active co-enzyme.
  • Pathway: PL-5′P binds to the active site of aminotransferases, decarboxylases, and glycogen phosphorylase, facilitating transfer of amino groups, decarboxylation of amino acids, and glycogen breakdown. In the trans-sulfuration pathway, PL-5′P-dependent cystathionine β-synthase converts homocysteine to cystathionine, lowering homocysteine levels. In the brain, PL-5′P is required for aromatic L-amino-acid decarboxylase (converting 5-HTP → serotonin) and glutamate decarboxylase (glutamate → GABA), thereby influencing neurotransmitter balance. PL-5′P also serves as a co-factor for sphingolipid synthesis and for the conversion of tryptophan to niacin, linking B6 status to both lipid metabolism and NAD⁺ biosynthesis.

Dosage

  • General adult supplementation: 1.3–2.0 mg/day (RDA) for most adults; up to 3 mg/day for pregnant women and 2 mg/day for lactating women.
  • Therapeutic uses: 10–25 mg/day for nausea in pregnancy; 50–100 mg/day (split doses) for peripheral neuropathy; 200–400 mg/day short-term (≤ 3 months) for severe homocysteine reduction under medical supervision.
  • Timing: Best taken with a meal containing protein to enhance absorption; split doses minimize potential sensory neuropathy.
  • Special populations: Elderly may benefit from 2–3 mg/day due to decreased absorption; athletes may require 2–5 mg/day for increased protein turnover.

Safety & Side Effects

  • Pyridoxine is well-tolerated at recommended doses.
  • High-dose chronic supplementation (>200 mg/day) can cause sensory peripheral neuropathy, reversible upon cessation.
  • Contraindications: Known hypersensitivity to pyridoxine, active peripheral neuropathy of unknown cause, and severe renal impairment (risk of accumulation).
  • Drug interactions: Potentiates the neurotoxic effects of isoniazid, may reduce efficacy of levodopa (Parkinson’s) unless combined with a dopa-decarboxylase inhibitor, and can enhance the hypoglycemic effect of insulin or sulfonylureas.
  • Pregnant women should not exceed 25 mg/day without medical guidance.
  • Children require age-adjusted doses (0.5–1 mg/day).

Chemistry

  • Pyridoxine (C₈H₁₁NO₃) has a molecular weight of 169.18 g/mol.
  • Its IUPAC name is 4-hydroxy-3-(hydroxymethyl)-2-methylpyridine-5-carboxylic acid.
  • The molecule consists of a pyridine ring substituted with a hydroxyl group at position 4, a methyl group at position 2, a hydroxymethyl side chain at position 3, and a carboxyl group at position 5.
  • The presence of a hydroxymethyl group and a 4-hydroxyl group makes pyridoxine relatively soluble in water (≈ 120 g/L at 25 °C) and moderately stable to heat and light.
  • The active co-enzyme, PL-5′P, is formed by oxidation of the hydroxymethyl group to an aldehyde (pyridoxal) followed by phosphorylation at the 5′-hydroxyl, yielding a highly polar phosphate ester.

Sources & Quality

  • Natural dietary sources include poultry, fish, organ meats, bananas, chickpeas, and fortified cereals.
  • Industrially, pyridoxine is produced by chemical synthesis from 2-methyl-4-hydroxy-5-nitro-pyridine via reduction and subsequent hydroxymethylation, yielding a high-purity (>99 %) crystalline powder.
  • Fermentation-based production (e.g., Bacillus spp.) is emerging as a “green” alternative.
  • For supplements, USP-grade pyridoxine is preferred; manufacturers must verify identity (HPLC), purity (absence of heavy metals), and stability (avoid exposure to light/humidity).
  • Standardized “pyridoxine HCl” is the most common form, providing predictable bioavailability, while pyridoxal-5′phosphate (the active form) is offered for individuals with conversion impairments.

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