Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis

Abstract

Patients with rheumatoid arthritis have subnormal vitamin B6 status, both quantitatively and functionally. Abnormal vitamin B6 status in rheumatoid arthritis has been associated with spontaneous tumor necrosis factor (TNF)-α production and markers of inflammation, including C-reactive protein and erythrocyte sedimentation rate. Impaired vitamin B6 status could be a result of inflammation, and these patients may have higher demand for vitamin B6. The aim of this study was to determine if daily supplementation with 50 mg of pyridoxine for 30 days can correct the static and/or the functional abnormalities of vitamin B6 status seen in patients with rheumatoid arthritis, and further investigate if pyridoxine supplementation has any effects on the pro-inflammatory cytokine TNF-α or IL-6 production of arthritis. This was a double-blinded, placebo-controlled study involving patients with rheumatoid arthritis with plasma pyridoxal 5'-phosphate below the 25th percentile of the Framingham Heart Cohort Study. Vitamin B6 status was assessed via plasma and erythrocyte pyridoxal 5'-phosphate concentrations, the erythrocyte aspartate aminotransferase activity coefficient (αEAST), net homocysteine increase in response to a methionine load test (ΔtHcy), and 24 h urinary xanthurenic acid (XA) excretion in response to a tryptophan load test. Urinary 4-pyridoxic acid (4-PA) was measured to examine the impact of pyridoxine treatment on vitamin B6 excretion in these patients. Pro-inflammatory cytokine (TNF-α and IL-6) production, C-reactive protein levels and the erythrocyte sedimentation rate before and after supplementation were also examined. Pyridoxine supplementation significantly improved plasma and erythrocyte pyridoxal 5'-phosphate concentrations, erythrocyte αEAST, urinary 4-PA, and XA excretion. These improvements were apparent regardless of baseline B6 levels. Pyridoxine supplementation also showed a trend (p < 0.09) towards a reduction in post-methionine load ΔtHcy. Supplementation did not affect pro-inflammatory cytokine production. Although pyridoxine supplementation did not suppress pro-inflammatory cytokine production in patients with rheumatoid arthritis, the suboptimal vitamin B6 status seen in rheumatoid arthritis can be corrected by 50 mg pyridoxine supplementation for 30 days. Data from the present study suggest that patients with rheumatoid arthritis may have higher requirements for vitamin B6 than those in a normal healthy population.

Blood lipid profiles and peripheral blood mononuclear cell cholesterol metabolism gene expression in patients with and without methotrexate treatment

“…Doses and durations of medication used by the study subjects are shown in Table 1 . The median weekly dose of MTX used in the subjects was 12.5 (mean ± SD = 10.3 ± 3.9 mg/week), which is slightly higher than that of our previous studies in the US [ 14 , 18 , 19 ].…”

Folinate Supplementation Ameliorates Methotrexate Induced Mitochondrial Formate Depletion In Vitro and In Vivo

“…Mice in the MTX+FA group received the same dose of MTX, with a folinate (0.1 mg folinate/kg body weight) treatment 24 h [ 39 ] after the MTX injection. MTX was generally administered to RA patients at a dosage of 7.5–15 mg/wk [ 40 , 41 , 42 ]; folinate is generally given at the dosage of 2.5 mg/wk [ 43 ]. Doses used in the present study are [ 42 ] comparable to those in humans, receiving a clinically low-dose MTX and folinate rescue [ 30 ].…”

Metabolism of Dietary and Microbial Vitamin B Family in the Regulation of Host Immunity

“…Vitamin B6 deficiency disrupts the Th1–Th2 balance toward an excessive Th2 response, resulting in allergy (85). Moreover, low plasma vitamin B6 levels, together with increased levels of pro-inflammatory cytokines such as TNF-α and IL-6, have been observed in patients with rheumatoid arthritis (86). However, the mechanism underlying the regulation of inflammation by vitamin B6 is currently unknown.…”