Vitamin B6 (Pyridoxine)
Pathophysiology—Pyridoxine is an important coenzyme for many functions including amino acid transamination, fatty acid metabolism, and conversion of tryptophan to niacin. It is absorbed in the jejunum and ileum and subsequently transported to the liver for rephosphorylation and release into its active form.36 An observational study assessing the nutritional status of patients with IBD found that only 5.7% of 105 patients with food records had inadequate dietary intake of pyridoxine, but 29% of all patients with IBD had subnormal pyridoxine levels.72 Additionally, they found no significant difference in the prevalence of subnormal pyridoxine levels in patients with active IBD vs IBD in remission. The authors suggested that the subnormal pyridoxine levels in patients with IBD likely were multifactorial and resulted from malabsorption due to active disease, inflammation, and inadequate intake.72
Cutaneous Manifestations—Cutaneous findings associated with pyridoxine deficiency include periorificial and perineal dermatitis,73 angular stomatitis, and cheilitis with associated burning, redness, and tongue edema.36 Additionally, pyridoxine is involved in the conversion of tryptophan to niacin, and its deficiency may manifest with pellagralike findings.74
Because pyridoxine is critical to protein metabolism, its deficiency may disrupt key cellular structures that rely on protein concentrations to maintain structural integrity. One such structure in the skin that heavily relies on protein concentrations is the ground substance of the extracellular matrix—the amorphous gelatinous spaces that occupy the areas between the extracellular matrix, which consists of cross-linked glycosaminoglycans and proteins.75 Without protein, ground substance increases in viscosity and can disrupt the epidermal barrier, leading to increased transepidermal water loss and ultimately inflammation.76 Although this theory has yet to be validated fully, this is a potential mechanistic explanation for the inflammation in dermal papillae that leads to dermatitis observed in pyridoxine deficiency.
Diagnosis and Monitoring—Direct biomarkers of pyridoxine status are in serum, plasma, erythrocytes, and urine, with the most common measurement in plasma as pyridoxal 5′-phosphate (PLP).77 Plasma PLP concentrations lower than 20 nmol/L are suggestive of deficiency.78 Plasma PLP has shown inverse relationships with acute phase inflammatory markers CRP79 and AP,78 thereby raising concerns for its validity to assess pyridoxine status in patients with symptomatic IBD.80
Alternative evaluations of pyridoxine include tryptophan and methionine loading tests,36 which are measured via urinary excretion and require normal kidney function to be accurate. They should be considered in IBD if necessary, but routine testing, even in patients with symptomatic IBD, is not recommended in the ECCO guidelines. Additional considerations should be taken in patients with altered nutrient requirements such as those who have undergone bowel resection due to highly active disease or those who receive parenteral nutritional supplementation.81
Treatment—Recommendations for oral pyridoxine supplementation range from 25 to 600 mg daily,82 with symptoms typically improving on 100 mg daily.36 Pyridoxine supplementation may have additional benefits for patients with IBD and potentially modulate disease severity. An IL-10 knockout mouse supplemented with pyridoxine had an approximately 60% reduction (P<.05) in inflammation compared to mice deficient in pyridoxine.83 The authors suggest that PLP-dependent enzymes can inhibit further proinflammatory signaling and T-cell migration that can exacerbate IBD. Ultimately, more data is needed before determining the efficacy of pyridoxine supplementation for active IBD.