Vitamin B6, Magnesium, and Vitamin D: The Triple Play

Vitamin B6, magnesium, and vitamin D are important antioxidants. Mg is a required cofactor for the synthesis of vitamin D and the active forms of vitamins B1,2,3,5,6,9,12 (seven of the eight B vitamins). Five of the seven (and magnesium) are critical to the methylation cycle, compromised by MTHFR (methylene tetrahydrofolate reductase) variants, present in the majority of Caucasians and Asians. Homocysteine (Hcy), a powerful pro-oxidant, is upregulated in these variants. Oxidative stress compromises mitochondrial function, required for the synthesis of the active form of vitamin D. Pyridoxal phosphate (P5P or PLP), the active form of B6, enhances the intracellular entry of magnesium and is required for the synthesis of the antioxidants melatonin and glutathione, oft called the “mother” of all antioxidants. Deficiencies of P5P and vitamin D are associated with decreased gut microbiota diversity and short chain fatty acids, e.g., butyrate, as seen in Long Covid (LC) and Chronic Fatigue Syndrome (CFS). This suboptimal gut microbiome reflects the continuing decline in the nutritional value of the Western diet. The interdependencies of and associations between P5P, magnesium, and 1,25(OH)2D, the active form of vitamin D, are explored.