Vitamin B6 is a water-soluble vitamin that is naturally present in many foods, added to others, and available as a dietary supplement. It is the generic name for six compounds (vitamers) with vitamin B6 activity: pyridoxine, an alcohol; pyridoxal, an aldehyde; and pyridoxamine, which contains an amino group; and their respective 5’-phosphate esters. Pyridoxal 5’ phosphate (PLP) and pyridoxamine 5’ phosphate (PMP) are the active coenzyme forms of vitamin B6 [1,2]. Substantial proportions of the naturally occurring pyridoxine in fruits, vegetables, and grains exist in glycosylated forms that exhibit reduced bioavailability .
Vitamin B6 in coenzyme forms performs a wide variety of functions in the body and is extremely versatile, with involvement in more than 100 enzyme reactions, mostly concerned with protein metabolism . Both PLP and PMP are involved in amino acid metabolism, and PLP is also involved in the metabolism of one-carbon units, carbohydrates, and lipids . Vitamin B6 also plays a role in cognitive development through the biosynthesis of neurotransmitters and in maintaining normal levels of homocysteine, an amino acid in the blood . Vitamin B6 is involved in gluconeogenesis and glycogenolysis, immune function (for example, it promotes lymphocyte and interleukin-2 production), and hemoglobin formation .
The human body absorbs vitamin B6 in the jejunum. Phosphorylated forms of the vitamin are dephosphorylated, and the pool of free vitamin B6 is absorbed by passive diffusion .
Vitamin B6 concentrations can be measured directly by assessing concentrations of PLP; other vitamers; or total vitamin B6 in plasma, erythrocytes, or urine . Vitamin B6 concentrations can also be measured indirectly by assessing either erythrocyte aminotransferase saturation by PLP or tryptophan metabolites. Plasma PLP is the most common measure of vitamin B6 status.
Vitamin B6 and Health:
Nausea and Vomiting in Pregnancy
About half of all women experience nausea and vomiting in the first few months of pregnancy, and about 50%–80% experience nausea only [27,28]. Although this condition is generally known as “morning sickness,” it often lasts throughout the day. The condition is not life threatening and typically goes away after 12–20 weeks, but its symptoms can disrupt a woman’s social and physical functioning.
Prospective studies on vitamin B6 supplements to treat morning sickness have had mixed results. In two randomized, placebo-controlled trials, 30–75 mg of oral pyridoxine per day significantly decreased nausea in pregnant women who were experiencing nausea [29,30]. The authors of a recent Cochrane review of studies on interventions for nausea and vomiting in pregnancy could not draw firm conclusions on the value of vitamin B6 to control the symptoms of morning sickness .
The American Congress of Obstetrics and Gynecology (ACOG) recommends monotherapy with 10–25 mg of vitamin B6 three or four times a day to treat nausea and vomiting in pregnancy . If the patient’s condition does not improve, ACOG recommends adding doxylamine. Before taking a vitamin B6 supplement, pregnant women should consult a physician because doses could approach the UL.
Scientists have hypothesized that certain B vitamins (folic acid, vitamin B12, and vitamin B6) might reduce cardiovascular disease risk by lowering homocysteine levels [1,15]. Therefore, several clinical trials have assessed the safety and efficacy of supplemental doses of B vitamins to reduce heart disease risk. Evaluating the impact of vitamin B6 from many of these trials is challenging because these studies also included folic acid and vitamin B12 supplementation. For example, the Heart Outcomes Prevention Evaluation 2 (HOPE 2) trial, which included more than 5,500 adults with known cardiovascular disease, found that supplementation for 5 years with vitamin B6 (50 mg/day), vitamin B12 (1 mg/day), and folic acid (2.5 mg/day) reduced homocysteine levels and decreased stroke risk by about 25%, but the study did not include a separate vitamin B6 group .
Moreover, most other large clinical trials have failed to demonstrate that supplemental B vitamins actually reduce the risk of cardiovascular events, even though they lower homocysteine levels. For example, a randomized clinical trial in 5,442 women aged 42 or older found no effect of vitamin B6 supplementation (50 mg/day) in combination with 2.5 mg folic acid and 1 mg vitamin B12 on cardiovascular disease risk . Two large randomized controlled trials, the Norwegian Vitamin Trial and the Western Norway B Vitamin Intervention Trial, did include a group that received only vitamin B6 supplements (40 mg/day). The combined analysis of data from these two trials showed no benefit of vitamin B6 supplementation, with or without folic acid (0.8 mg/day) plus vitamin B12 (0.4 mg/day), on major cardiovascular events in 6,837 patients with ischemic heart disease . In a trial of adults who had suffered a nondisabling stroke, supplementation with high or low doses of a combination of vitamins B6 and B12 and folic acid for 2 years had no effect on subsequent stroke incidence, cardiovascular events, or risk of death .
The research to date provides little evidence that supplemental amounts of vitamin B6, alone or with folic acid and vitamin B12, can help reduce the risk or severity of cardiovascular disease and stroke.
Some research has associated low plasma vitamin B6 concentrations with an increased risk of certain kinds of cancer . For example, a meta-analysis of prospective studies found that people with a vitamin B6 intake in the highest quintile had a 20% lower risk of colorectal cancer than those with an intake in the lowest quintile .
However, the small number of clinical trials completed to date has not shown that vitamin B6 supplementation can help prevent cancer or reduce its impact on mortality. For example, an analysis of data from two large randomized, double-blind, placebo-controlled trials in Norway found no association between vitamin B6 supplementation and cancer incidence, mortality, or all-cause mortality .
Poor vitamin B6 status has been hypothesized to play a role in the cognitive decline that some older adults experience . Several studies have demonstrated an association between vitamin B6 and brain function in the elderly. For example, an analysis of data from the Boston Normative Aging Study found associations between higher serum vitamin B6 concentrations and better memory test scores in 70 men aged 54–81 years .
However, a systematic review of 14 randomized controlled trials found insufficient evidence of an effect of vitamin B6 supplementation alone or in combination with vitamin B12 and/or folic acid on cognitive function in people with normal cognitive function, dementia, or ischemic vascular disease . According to this review, most of the studies were of low quality and limited applicability. A Cochrane review found no evidence that short-term vitamin B6 supplementation (for 5–12 weeks) improves cognitive function or mood in the two studies that the authors evaluated . The review did find some evidence that daily vitamin B6 supplements (20 mg) can affect biochemical indices of vitamin B6 status in healthy older men, but these changes had no overall impact on cognition.
More evidence is needed to determine whether vitamin B6 supplements might help prevent or treat cognitive decline in elderly people.
Some evidence suggests that vitamin B6 supplements could reduce the symptoms of premenstrual syndrome (PMS), but conclusions are limited due to the poor quality of most studies . A meta-analysis of nine published trials involving almost 1,000 women with PMS found that vitamin B6 is more effective in reducing PMS symptoms than placebo, but most of the studies analyzed were small and several had methodological weaknesses . A more recent double-blind, randomized controlled trial in 94 women found that 80 mg pyridoxine taken daily over the course of three cycles was associated with statistically significant reductions in a broad range of PMS symptoms, including moodiness, irritability, forgetfulness, bloating, and, especially, anxiety . The potential effectiveness of vitamin B6 in alleviating the mood-related symptoms of PMS could be due to its role as a cofactor in neurotransmitter biosynthesis . Although vitamin B6 shows promise for alleviating PMS symptoms, more research is needed before drawing firm conclusions.