ESA Resistance Linked to Vitamin B6 Treatment
IV administration of vitamin B6 did not improve anemia or abnormal bone metabolism over 6 months.
Intravenous (IV) vitamin B6 administered 3 times per week may reduce response to erythropoiesis-stimulating agents (ESA).
In a pilot study, Japanese investigators led by Yoshitsugu Obi, MD, PhD, of Osaka University, and Satoshi Mikami, MD, PhD, of Higashikouri Hospital, tested whether vitamin B6 supplementation could improve response to anemia treatment. They randomly assigned 56 maintenance hemodialysis (HD) patients with relatively high resistance to ESA agents to a treatment arm in which patients received 60 mg of IV pyridoxal 5'-phosphate (PLP) at the end of each dialysis session or to a control arm in which patients received standard care but received no PLP. Overall, 40% of patients were vitamin B6 deficient.
Surprisingly, the B6 group experienced a rise in the ESA resistance index (ERI) over 6 months compared with the control group, according to results published in the Journal of Renal Nutrition. IV vitamin B6 treatment was associated with higher ERI at week 13 by 0.97 x 10-2 µg darbepoetin-alpha per kg of weight per g/dL of hemoglobin, regardless of patients' vitamin B6 status at baseline. Meanwhile, endogenous erythropoietin levels increased in the B6 group (after adjustment for hemoglobin and ESA dose), perhaps as a compensatory response.
“Intravenous vitamin B6 administration did not offer significant benefit, even in patients with deficiency in terms of anemia and bone metabolism, suggesting that vitamin B6 deficiency may not always be involved in the pathways causal of these complications,” stated Dr Obi, Dr Mikami, and colleagues. Alternatively, the cutoff for deficiency may be inappropriate, they noted.
Certain markers of bone turnover— bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b – trended downward in the B6 group among those without vitamin B6 deficiency. “These results suggested vitamin B6 toxicity in the intervention group,” according to the investigators. The dose of pyridoxal 5'-phosphate may be too high for HD patients. (No serious adverse events associated with vitamin B6 toxicity were reported.) The investigators concluded that IV treatment with vitamin B6 may blunt the response of bone to parathyroid hormone.
Most previous studies have shown no benefit for vitamin B supplementation, and some potential harms. A single study of oral pyridoxine conducted in 2001 showed no changes in hemoglobin (Nephron. 2001;87:328-332).
Chugai Pharmaceutical Co., Ltd, partially funded the current study and supplied IV pyridoxal 5'-phosphate. Some of the authors disclosed honoraria and research grant support from the company.
1. Obi Y, Mikami S, Hamano T, et al. Intravenous Vitamin B6 Increases Resistance to Erythropoiesis-Stimulating Agents in Hemodialysis Patients: A Randomized Controlled Trial. J Ren Nutr. 2016 Jul 27. pii: S1051-2276(16)30054-1. doi: 10.1053/j.jrn.2016.06.004. [Epub ahead of print]