Dr. Ron’s Research Review – January 19, 2011

This week’s research review contains information on the P5P.

Pyridoxal phosphate is the cofactor for over 100 enzyme-catalysed reactions in the body, including many involved in the synthesis or catabolism of neurotransmitters. Inadequate levels of pyridoxal phosphate in the brain cause neurological dysfunction, particularly epilepsy. (Clayton 2006)

There is evidence to suggest that absorption of B6 vitamers is impaired in celiac disease. Surprisingly, PLP concentrations in plasma are still low in some patients who have been on a gluten-free diet for 10 years. (Clayton 2006)

Vitamin B-6 intake is inversely related to, and the requirement is affected by, inflammation status. (Morris, Sakakeeny et al. 2010)

Both deficiency and excess of pyridoxine can cause neurological symptoms. Cases of neuropathy from excess pyridoxine have been reported in doses of greater than 600 mg per day, although may occur in some individuals at doses as low as 300-500 mg. Several sources recommend 100 mg as a safe dose. (CRN 2004).

Pyridoxine (vitamin B6) neurotoxicity was enhanced by a protein-deficient diet. Large doses of pyridoxine were required in order to demonstrate neurotoxicity. (Levine and Saltzman 2004)

Dr. Ron


Articles

B6-responsive disorders: a model of vitamin dependency

            (Clayton 2006) Download

Pyridoxal phosphate is the cofactor for over 100 enzyme-catalysed reactions in the body, including many involved in the synthesis or catabolism of neurotransmitters. Inadequate levels of pyridoxal phosphate in the brain cause neurological dysfunction, particularly epilepsy. There are several different mechanisms that lead to an increased requirement for pyridoxine and/or pyridoxal phosphate. These include: (i) inborn errors affecting the pathways of B(6) vitamer metabolism; (ii) inborn errors that lead to accumulation of small molecules that react with pyridoxal phosphate and inactivate it; (iii) drugs that react with pyridoxal phosphate; (iv) coeliac disease, which is thought to lead to malabsorption of B(6) vitamers; (v) renal dialysis, which leads to increased losses of B(6) vitamers from the circulation; (vi) drugs that affect the metabolism of B(6) vitamers; and (vii) inborn errors affecting specific pyridoxal phosphate-dependent enzymes. The last show a very variable degree of pyridoxine responsiveness, from 90% in X-linked sideroblastic anaemia (delta-aminolevulinate synthase deficiency) through 50% in homocystinuria (cystathionine beta-synthase deficiency) to 5% in ornithinaemia with gyrate atrophy (ornithine delta-aminotransferase deficiency). The possible role of pyridoxal phosphate as a chaperone during folding of nascent enzymes is discussed. High-dose pyridoxine or pyridoxal phosphate may have deleterious side-effects (particularly peripheral neuropathy with pyridoxine) and this must be considered in treatment regimes. None the less, in some patients, particularly infants with intractable epilepsy, treatment with pyridoxine or pyridoxal phosphate can be life-saving, and in other infants with inborn errors of metabolism B(6) treatment can be extremely beneficial.

Safety of pyridoxine--a review of human and animal studies

            (Cohen and Bendich 1986) Download

A literature review was conducted on adverse effects associated with administration of high oral doses of pyridoxine (vitamin B6) to animals and man. The human data suggest that doses of pyridoxine greater than 500 mg/day for prolonged periods of time can result in sensory nerve damage. Doses less than 500 mg/day appear to be safe on the basis of literature reports where the compound was administered for periods ranging from 6 months to 6 years.

CRN 2004 - Safety of vitamin B6

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Pyridoxine (vitamin B6) neurotoxicity: enhancement by protein-deficient diet

            (Levine and Saltzman 2004) Download

Large doses of pyridoxine cause injury to the primary sensory neurons in trigeminal and dorsal root ganglia of animals and patients subjected to megavitamin therapy. The increased hazard to subjects with reduced renal excretory function has been explored previously. In the present work, the neurotoxicity of pyridoxine for rats was found to be increased by dietary protein deficiency. A mere 3 or 7 days of pretreatment with either of two protein-deficient diets were sufficient to accelerate and intensify the clinical neurological signs and histological lesions from pyridoxine injections. These results are caused, at least in part, by loss of body weight, decreased protein binding in serum and decreased consumption of water and decreased volume of urine, which reduce the urinary losses of the toxicant. The vitamers related to pyridoxine (pyridoxal, pyridoxamine) and the coenzyme (pyridoxal 5-phosphate) did not cause clinical signs or lesions similar to those produced by pyridoxine even when injected in maximum tolerated doses. Neither a protein-deficient diet nor bilateral nephrectomy changed the results with the vitamers.

Vitamin B-6 intake is inversely related to, and the requirement is affected by, inflammation status

            (Morris, Sakakeeny et al. 2010) Download

Low circulating pyridoxal 5'-phosphate (PLP) concentrations have been linked to inflammatory markers and the occurrence of inflammatory diseases. However, the implications of these findings are unclear. The measurement of PLP and C-reactive protein (CRP) in blood samples collected from participants in the 2003-2004 NHANES afforded us the opportunity to investigate this relationship in the general U.S. population. Dietary and laboratory data were available for 3864 of 5041 interviewed adults, 2686 of whom were eligible (i.e. provided reliable dietary data and were not diabetic, pregnant, lactating, or taking hormones or steroidal antiinflammatory drugs). Vitamin B-6 intake was assessed using 2 24-h diet recalls and supplement use data. After multivariate adjustment for demographics, smoking, BMI, alcohol use, antioxidant vitamin status, intakes of protein and energy, and serum concentrations of creatinine and albumin, high vitamin B-6 intake was associated with protection against serum CRP concentrations >10 mg/L compared with < or =3 mg/L. However, plasma PLP > or =20 nmol/L compared with <20 nmol/L was inversely related to serum CRP independently of vitamin B-6 intake (P < 0.001). Among participants with vitamin B-6 intakes from 2 to 3 mg/d, the multivariate-adjusted prevalence of vitamin B-6 inadequacy was <10% in participants with serum CRP < or =3 mg/L but close to 50% in those with serum CRP > 10 mg/L (P < 0.001). In conclusion, higher vitamin B-6 intakes were linked to protection against inflammation and the vitamin B-6 intake associated with maximum protection against vitamin B-6 inadequacy was increased in the presence compared to absence of inflammation.


References

Clayton, P. T. (2006). "B6-responsive disorders: a model of vitamin dependency." J Inherit Metab Dis 29(2-3): 317-26.

Levine, S. and A. Saltzman (2004). "Pyridoxine (vitamin B6) neurotoxicity: enhancement by protein-deficient diet." J Appl Toxicol 24(6): 497-500.