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vitamin b6

Vitamin B6

Vitamin B6 is a water-soluble vitamin that is naturally present in many foods, added to others, and available as a dietary supplement. Vitamin B6 is the generic name for six compounds (vitamers) with vitamin B6 activity (Figure 1) 1, 2, 3, 4, 5, 6:

  • Pyridoxine (pyridoxol) an alcohol, commonly known as vitamin B6;
  • Pyridoxal, an aldehyde;
  • 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 involved in over 4% of all enzymatic reactions.

Vitamin B6 must be obtained from the diet because humans cannot synthesize it 7. Vitamin B6 is a vitamin that is naturally present in many foods. You can get recommended amounts of vitamin B6 by eating a variety of foods, including the following 8:

  • Poultry, fish, and organ meats, all rich in vitamin B6.
  • Potatoes and other starchy vegetables, which are some of the major sources of vitamin B6 for Americans.
  • Fruit (other than citrus), which are also among the major sources of vitamin B6 for Americans.

Your body needs vitamin B6 for more than 100 enzyme reactions, mostly concerned with protein metabolism 9. Vitamin B6 is also involved in brain development during pregnancy and infancy as well as immune function 8. Both pyridoxal 5’ phosphate (PLP) and pyridoxamine 5’ phosphate (PMP) are involved in amino acid metabolism, and pyridoxal 5’ phosphate (PLP) is also involved in the metabolism of one-carbon units, carbohydrates, and lipids 10. 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 10. Vitamin B6 is involved in gluconeogenesis (metabolic pathway that results in the generation of glucose or sugar from certain non-carbohydrate breakdown products of lipids (fats) or proteins) and glycogenolysis (metabolic pathway in which glycogen breaks down into glucose or sugar), immune function (for example, it promotes lymphocyte and interleukin-2 production), and hemoglobin formation 10.

Your body absorbs vitamin B6 in the jejunum, the second part of your small intestine. Phosphorylated forms of vitamin B6 are dephosphorylated, and the pool of free vitamin B6 is absorbed by passive diffusion 2. In fruit and vegetables, vitamin B6 is present principally as pyridoxine and its phosphate and glucoside 11. In meat and fish, vitamin B6 is mainly present as pyridoxal 5’ phosphate (PLP) and pyridoxamine 5’ phosphate (PMP) 11. Synthesis of vitamin B6 by the gut microbiota (microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of humans) can make a significant contribution to your vitamin B6 intake and may explain why dietary vitamin B6 deficiency is rare 12. Vitamin B6 deficiency or pyridoxine deficiency can occur in the first year of life when the gut flora is not fully established 11; in the 1950s, infants fed a milk formula that had been overheated during production developed seizures due to vitamin B6 deficiency (pyridoxine deficiency) 13.

Vitamin B6 concentrations can be measured directly by assessing concentrations of pyridoxal 5’ phosphate (PLP); other vitamers; or total vitamin B6 in plasma, red blood cells, or urine 9. Vitamin B6 concentrations can also be measured indirectly by assessing either red blood cell aminotransferase saturation by pyridoxal 5’ phosphate (PLP) or tryptophan metabolites. Plasma pyridoxal 5’ phosphate (PLP) is the most common measure of vitamin B6 status 14.

PLP concentrations of more than 30 nmol/L have been traditional indicators of adequate vitamin B6 status in adults 10. However, the Food and Nutrition Board at the Institute of Medicine of the National Academies used a plasma PLP level of 20 nmol/L as the major indicator of adequacy to calculate the Recommended Dietary Allowances (RDAs) for adults 9, 10.

Figure 1. Vitamin B6 chemical structures

Vitamin B6 chemical structures
vitamin B6
[Source 11 ]

What does Vitamin B6 do?

Vitamin B6 includes a group of closely related compounds: pyridoxine, pyridoxal, and pyridoxamine and pyridoxamine 5’ phosphate (PMP) with pyridoxal 5’ phosphate (PLP) being the only active vitamin B6 vitamer that acts as a cofactor involved in over 100 enzymes that catalyze essential chemical reactions in the human body, a role that is enabled by its reactive aldehyde group 15. Your body needs vitamin B6 for more than 100 enzyme reactions, mostly concerned with protein metabolism 9. Vitamin B6 is also involved in brain development during pregnancy and infancy as well as immune function 8. Both pyridoxal 5’ phosphate (PLP) and pyridoxamine 5’ phosphate (PMP) are involved in amino acid metabolism, and pyridoxal 5’ phosphate (PLP) is also involved in the metabolism of one-carbon units, carbohydrates, and lipids 10. 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 10. Vitamin B6 is involved in gluconeogenesis (metabolic pathway that results in the generation of glucose or sugar from certain non-carbohydrate breakdown products of lipids (fats) or proteins) and glycogenolysis (metabolic pathway in which glycogen breaks down into glucose or sugar), immune function (for example, it promotes lymphocyte and interleukin-2 production), and hemoglobin formation 10.

Pyridoxal 5’ phosphate (PLP) dependent enzymes have been classified into five structural classes known as Fold Type 1-5 16:

  • Fold Type 1 – aspartate aminotransferase family
  • Fold Type 2 – tryptophan synthase family
  • Fold Type 3 – alanine racemase family
  • Fold Type 4 – D-amino acid aminotransferase family
  • Fold Type 5 – glycogen phosphorylase family

The many biochemical reactions catalyzed by PLP-dependent enzymes are involved in essential biological processes, such as hemoglobin and amino acid biosynthesis, as well as fatty acid metabolism. Of note, PLP also functions as a coenzyme for glycogen phosphorylase, an enzyme that catalyzes the release of glucose from stored glycogen 7. Much of the PLP in the human body is found in muscle bound to glycogen phosphorylase. PLP is also a coenzyme for reactions that generate glucose from amino acids, a process known as gluconeogenesis 17.

Pyridoxine Vitamin B6 rich food sources

Nervous system function

In the brain, the pyridoxal 5’ phosphate (PLP)-dependent enzyme aromatic L-amino acid decarboxylase catalyzes the synthesis of two major neurotransmitters: serotonin from the amino acid tryptophan and dopamine from L-3,4-dihydroxyphenylalanine (L-Dopa) 7. Other neurotransmitters, including glycine, D-serine, glutamate, histamine, and γ-aminobutyric acid (GABA), are also synthesized in reactions catalyzed by pyridoxal 5’ phosphate (PLP)-dependent enzymes 18.

Hemoglobin synthesis and function

Pyridoxal 5’ phosphate (PLP) functions as a coenzyme of 5-aminolevulinic acid synthase, which is involved in the synthesis of heme, an iron-containing component of hemoglobin 7. Hemoglobin is found in red blood cells and is critical to their ability to transport oxygen throughout the body. Both pyridoxal and pyridoxal 5’ phosphate (PLP) are able to bind to the hemoglobin molecule and affect its ability to pick up and release oxygen. However, the impact of this on normal oxygen delivery to tissues is not known 17, 19. Vitamin B6 deficiency may impair hemoglobin synthesis and lead to microcytic anemia 4.

Tryptophan metabolism

Deficiency in vitamin B3, Niacin, is easily prevented by adequate dietary intakes. The dietary requirement for niacin (vitamin B3) and the niacin coenzyme, nicotinamide adenine dinucleotide (NAD), can be also met, though to a fairly limited extent, by the catabolism of the essential amino acid tryptophan in the tryptophan-kynurenine pathway (Figure 2). Key reactions in the tryptophan-kynurenine metabolic pathway are pyridoxal 5’ phosphate (PLP)-dependent; in particular, pyridoxal 5’ phosphate (PLP) is the cofactor for the enzyme kynureninase, which catalyzes the conversion of 3-hydroxykynurenine to 3-hydroxyanthranilic acid 7. A reduction in PLP availability appears to primarily affect kynureninase activity, limiting NAD production and leading to higher concentrations of kynurenine, 3-hydroxykynurenine, and xanthurenic acid in blood and urine (Figure 2) 20. Thus, while dietary vitamin B6 restriction impairs nicotinamide adenine dinucleotide (NAD) synthesis from tryptophan, adequate PLP levels help maintain NAD formation from tryptophan 21. The effect of vitamin B6 inadequacy on immune activation and inflammation may be partly related to the role of PLP in the tryptophan-kynurenine metabolism 7.

Figure 2.  Tryptophan-kynurenine pathway

Tryptophan-kynurenine metabolic pathway
[Source 7 ]

Hormone function

Steroid hormones, such as estrogen and testosterone, exert their effects in the body by binding to steroid hormone receptors in the nucleus of target cells. The nuclear receptors themselves bind to specific regulatory sequences in DNA and alter the transcription of target genes. Experimental studies have uncovered a mechanism by which PLP may affect the activity of steroid receptors and decrease their effects on gene expression. It was found that PLP could interact with RIP140/NRIP1, a repressor of nuclear receptors known for its role in reproductive biology 22. Yet, additional research is needed to confirm that this interaction can enhance RIP140/NRIP1 repressive activity on steroid receptor-mediated gene expression. If the activity of steroid receptors for estrogen, progesterone, testosterone, or other steroid hormones can be inhibited by PLP, it is possible that vitamin B6 status may influence one’s risk of developing diseases driven by steroid hormones, such as breast and prostate cancers 17.

Nucleic acid synthesis

The synthesis of nucleic acids from precursors thymidine and purines is dependent on folate coenzymes. The de novo thymidylate (dTMP) biosynthesis pathway involves three enzymes: dihydrofolate reductase (DHFR), serine hydroxymethyltransferase (SHMT), and thymidylate synthase (TYMS) (Figure 3) 7. PLP serves as a coenzyme for serine hydroxymethyltransferase (SHMT), which catalyzes the simultaneous conversions of serine to glycine and tetrahydrofolate (THF) to 5,10-methylene THF 7. The latter molecule is the one-carbon donor for the generation of dTMP from deoxyuridine monophosphate (dUMP) by thymidylate synthase (TYMS) 7.

Figure 3. Vitamin B6 in nucleic acid synthesis

Vitamin B6 in nucleic acid synthesis
[Source 7 ]

Vitamin B6 Benefits

Scientists are studying vitamin B6 to understand how it affects health. Here are some examples of what this research has shown.

Cardiovascular disease

Scientists have hypothesized that certain B vitamins (such as folic acid [vitamin B9], vitamin B12 [cyanocobalamin], and vitamin B6 [pyridoxine]) might reduce cardiovascular disease risk lowering levels of homocysteine, an amino acid in the blood 1, 23. Therefore, several clinical trials have assessed the safety and effectiveness 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 24.

The use of multivitamin supplements (including vitamin B6) has been associated with a 24% lower risk of incidental coronary artery disease (coronary heart disease) in a large prospective study of 80,082 women from the US Nurses’ Health Study cohort 25. Coronary artery disease (coronary heart disease) is characterized by the abnormal stenosis (narrowing) of coronary arteries (generally due to atherosclerosis), which can result in a potentially fatal myocardial infarction (heart attack). Using food frequency questionnaires, the authors observed that women in the highest quintile of vitamin B6 intakes from both food and supplements (median, 4.6 mg/day) had a 34% lower risk of coronary artery disease (coronary heart disease) compared to those in the lowest quintile (median, 1.1 mg/day) 25. More recently, a prospective study that followed a Japanese cohort of over 40,000 middle-aged individuals for 11.5 years reported a 48% lower risk of myocardial infarction in those in the highest (mean, 1.6 mg/day) versus lowest quintile (mean, 1.3 mg/day) of vitamin B6 intakes in non-supplement users 26.

Early observational studies have also demonstrated an association between suboptimal pyridoxal 5′-phosphate (PLP) plasma level, elevated homocysteine blood level, and increased risk of cardiovascular disease 27, 28, 29. More recent research has confirmed that low plasma pyridoxal 5’ phosphate (PLP) status is a risk factor for coronary artery disease. In a case-control study, which included 184 participants with coronary artery disease and 516 healthy controls, low plasma PLP levels (<30 nanomoles/liter) were associated with a near doubling of coronary artery disease risk when compared to higher PLP levels (≥30 nanomoles/liter) 30. In a nested case-control study based on the Nurses’ Health Study cohort and including 144 cases of myocardial infarction (of which 21 were fatal), women in the highest quartile of blood PLP levels (≥70 nanomoles/liter) had a 79% lower risk of myocardial infarction compared to those in the lowest quartile (<27.9 nanomoles/liter) 31.

Even moderately elevated levels of homocysteine in the blood have been associated with increased risk for cardiovascular disease, including heart failure (cardiac insufficiency), coronary artery disease, heart attack (myocardial infarction), and stroke (cerebrovascular accident) 32, 33, 34, 35. During protein digestion, amino acids, including methionine, are released. Methionine is an essential amino acid and precursor of S-adenosylmethionine (SAM), the universal methyl donor for most methylation reactions, including the methylation of DNA, RNA, proteins, and phospholipids 7. Homocysteine is an intermediate in the metabolism of methionine. Healthy individuals utilize two different pathways to regenerate methionine from homocysteine in the methionine remethylation cycle (Figure 4). One pathway relies on the vitamin B12-dependent methionine synthase and the methyl donor, 5-methyl tetrahydrofolate (a folate derivative), to convert homocysteine back to methionine. The other reaction is catalyzed by betaine homocysteine methyltransferase, which uses betaine as a source of methyl groups for the formation of methionine from homocysteine. Moreover, two PLP-dependent enzymes are required to convert homocysteine to the amino acid cysteine in homocysteine transsulfuration pathway: cystathionine β synthase and cystathionine γ lyase (Figure 4). Thus, the amount of homocysteine in the blood may be influenced by nutritional status of at least three B vitamins, namely folate, vitamin B12, and vitamin B6.

Deficiencies in one or all of these B vitamins may affect both remethylation and transsulfuration processes and result in abnormally elevated homocysteine levels. An early study found that vitamin B6 supplementation could lower blood homocysteine levels after an oral dose of methionine was given (i.e., a methionine load test) 36, but vitamin B6 supplementation might not be effective in decreasing fasting levels of homocysteine. In a recent study conducted in nine healthy young volunteers, the rise of homocysteine during the postprandial period (after a meal) was found to be greater with marginal vitamin B6 deficiency (mean plasma PLP level of 19 nanomoles/liter) as compared to vitamin B6 sufficiency (mean PLP level of 49 nanomoles/liter) 37. The authors reported an increased rate of cystathionine synthesis with vitamin B6 restriction, suggesting that homocysteine catabolism in the transsulfuration may be maintained or enhanced in response to a marginal reduction in PLP availability. Yet, the flux ratio between methionine cycle and transsulfuration pathway appeared to favor homocysteine clearance by remethylation rather than transsulfuration in six out of nine participants 37.

Numerous randomized controlled trials, many in subjects with existing hyperhomocysteinemia and vascular dysfunction, have demonstrated that supplementation with folic acid, alone or combined with vitamin B6 and vitamin B12, could effectively reduce fasting plasma homocysteine concentrations. In 19 intervention studies recently included in a meta-analysis, reductions in homocysteine level in the blood following B-vitamin supplementation ranged between 7.6% and 51.7% compared to baseline levels 38. In contrast, studies supplementing individuals with only vitamin B6 have usually failed to show an effect on fasting levels of homocysteine 39, 40. Of the three supplemental B vitamins, folic acid appears to be the main determinant in the regulation of fasting homocysteine levels when there is no coexisting deficiency of vitamin B12 or vitamin B6 41. Yet, the effect of homocysteine lowering on cardiovascular disease risk reduction is debated. A recent meta-analysis of nine randomized controlled trials reported a 10% reduction in stroke events with supplemental B vitamins, with greater benefits for high-risk subjects (e.g., those with kidney disease) 42. However, most systematic reviews and meta-analyses of B-vitamin intervention studies to date have indicated a lack of causality between the decrease of fasting homocysteine levels and the prevention of cardiovascular events 43, 44, 38, 45. Moreover, B-vitamin supplementation trials in high-risk subjects have not resulted in significant changes in carotid intima-media thickness and flow-mediated dilation of the brachial artery, two markers of vascular health used to assess atherosclerotic progression 46. Finally, in the Western Norway B Vitamin Intervention Trial (WENBIT), a randomized, double-blind, placebo-controlled trial in 87 subjects with suspected coronary heart disease, vitamin B6 supplementation (40 mg/day of pyridoxine) for a median of 10 months had no effect on coronary stenosis progression, assessed by quantitative angiography 47.

Although vitamin B supplements do lower blood homocysteine levels, large clinical trials have failed to demonstrate that supplemental B vitamins reduce the risk or severity of heart disease or stroke 14. 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 48. Two large randomized controlled trials, the Norwegian Vitamin Trial and the Western Norway B Vitamin Intervention Trial (WENBIT), 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 23. 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 49.

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 14.

Figure 4. Homocysteine metabolism

Homocysteine metabolism

Footnotes: Schematic representation of pathways of homocysteine metabolism, which include a system of transmethylation, remethylation, and transsulfuration paths. In most cells, by transmethylation route homocysteine and methionine cycle metabolically, the methyl group on activated methionine (S-adenosyl-methionine or SAM) may be added to methyl acceptors (DNA, RNA, and protein) by methyltransferases, and the S-adenosyl-homocysteine (SAH) is rapidly hydrolyzed to adenosine and homocysteine, which could improve its concentration 50. Transmethylations, chemical reactions transferring a methyl group from one compound to another, are generally regulated by the intracellular concentration of involved compounds; thus, S-adenosyl-methionine (SAM) and S-adenosyl-homocysteine (SAH) concentrations determine a cell’s methylation balance. Once formed, homocysteine can be recycled into methionine or converted into cysteine by remethylation and transsulfuration routes, respectively. homocysteine is remethylated to methionine through two separate reactions catalyzed by three different enzymes. In all tissues, folic acid donates a methyl group across methylenetetrahydrofolate reductase (MTHFR) in a reaction catalyzed by methionine synthase, a vitamin-B12-dependent enzyme 51. Otherwise, mainly in the human heart, liver, and kidneys, homocysteine is remethylated using betaine, which donates a methyl group by betaine-homocysteine S-methyltransferase (BHMT) by a route independent of the one-carbon metabolism. Betaine can be found in several dietary sources, including wheat germ or bran, spinach, beets, seafood, and legumes. Studies have confirmed betaine’s ability to reduce homocysteine levels in the face of excess methionine intake, as well as the fact that low-dose betaine supplementation leads to immediate and long-term lowering of plasma homocysteine in healthy men and women 52, 53. This remethylation process begins when there are low concentrations of homocysteine and methionine 54. Alternately, mainly in the liver, but also in the kidneys, small intestine, and pancreas 55, homocysteine is enzymatically modified by cystathionine-β-synthase, a B6-dependent enzyme, to irreversibly form cysteine through the intermediate cystathionine. The transsulfuration route results in sulfur metabolites including GSH, a key cellular antioxidant, and hydrogen sulfide (H2S), acting like a gaseous signaling molecule. The transsulfuration path starts to function when the concentrations of homocysteine and methionine increase, for example by post-prandial protein intake 56, or cysteine is needed.

Abbreviations: DHFR = dihydrofolate reductase; THF = tetrahydrofolate; SHMT = serinehydroxymethyltransferase; MTHF = methylenetetrahydrofolate; MTHFR = 5,10-methylene-THF reductase; ATP = adenosine triphosphate; MAT = methionine adenosyltransferase; ADP = adenosine diphosphate; SAM = S-adenosylmethionine; SAH = S-adenosylHcy; BHMT = betaine-Hcy S-methyltransferase; CBS = cystathionine β-synthase; CSE = cystathionase; GSH = glutathione; H2S = hydrogen sulphide.

[Source 50 ]

Cancer

Some research has associated low plasma vitamin B6 concentrations with an increased risk of certain kinds of cancer, such as colorectal cancer 10. 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 57.

Inconsistent evidence regarding the link between vitamin B6 intakes and breast cancer was also recently reported in a meta-analysis 58. Yet, a prospective study that followed nearly 500,000 older adults for nine years observed that the risk of esophageal and stomach cancers was lower in participants in the highest versus lowest quintile of total vitamin B6 intakes (median values, 2.7 mg/day vs. 1.4 mg/day) 59. Additionally, a meta-analysis of four nested case-control studies reported a 48% reduction in colorectal cancer risk in the highest versus lowest quartile of blood PLP level 57. Another meta-analysis of five nested case-control studies found higher versus lower serum PLP levels to be associated with a 29% lower risk of breast cancer in postmenopausal, but not premenopausal, women 58.

Very few randomized, placebo-controlled trials investigating the nature of the association between B vitamins and cancer risk have focused on vitamin B6. Two earlier studies conducted in subjects with coronary artery disease failed to observe any benefit of supplemental vitamin B6 (40 mg/day) on colorectal cancer risk and mortality 60. A recent randomized, double-blind, placebo-controlled study conducted in 1,470 women with high cardiovascular risk showed that daily supplementation with 2.5 mg of folic acid, 1 mg of vitamin B12, and 50 mg of vitamin B6 for a mean treatment period of 7.3 years had no effect on the risk of developing colorectal adenoma when compared to placebo 61.

However, the small number of clinical trials completed to date has not shown that vitamin B6 supplementation can help prevent cancer or lower the chances of dying from cancer. 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 62.

Cognitive function

Some research indicates that elderly people who have higher blood levels of vitamin B6 have better memory. A few observational studies have linked cognitive decline and Alzheimer’s disease in the elderly with inadequate status of folate, vitamin B12, and vitamin B6 63. Poor vitamin B6 status has been hypothesized to play a role in the cognitive decline that some older adults experience 64. 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 65.

Yet, the relationship between B vitamins and cognitive health in aging is complicated by both the high prevalence of high serum homocysteine (hyperhomocysteinemia) and signs of systemic inflammation in elderly people 66. On the one hand, since inflammation may impair vitamin B6 metabolism, low serum PLP levels may well be caused by processes related to aging rather than by malnutrition. On the other hand, high serum homocysteine may possibly be a risk factor for cognitive decline in the elderly, although the matter remains under debate. Specifically, the meta-analysis of 19 randomized, placebo-controlled trials of B-vitamin supplementation failed to report any difference in several measures of cognitive function between treatment and placebo groups, despite the treatment effectively lowering homocysteine levels 67. In a recent randomized, double-blind, placebo-controlled study of 2,695 stroke survivors with or without cognitive impairments, daily supplementation with 2 mg of folic acid, 0.5 mg of vitamin B12, and 25 mg of vitamin B6 for 3.4 years resulted in significant reductions in mean homocysteine levels (by 28% and 43% in cognitively unimpaired and impaired patients, respectively) compared to placebo 68. Yet, the B-vitamin intervention had no effect on either the incidence of newly diagnosed cognitive impairments or on measures of cognitive performance when compared to placebo 68. In contrast, another recent placebo-controlled trial found that a daily B-vitamin regimen that led to significant homocysteine lowering in high-risk elderly individuals could limit the progressive atrophy of gray matter brain regions associated with the Alzheimer’s disease process 69. Yet, the authors attributed the changes in homocysteine levels primarily to vitamin B12 69. Because of mixed findings, it is presently unclear whether supplementation with B vitamins might blunt cognitive decline in the elderly. Furthermore, taking vitamin B6 supplements (alone or combined with vitamin B12 and/or folic acid) does not seem to improve cognitive function or mood in healthy people or in people with dementia.

More evidence is needed to determine whether marginal B-vitamin deficiencies, which are relatively common in the elderly, even contribute to age-associated declines in cognitive function, or whether vitamin B6 supplements might help prevent or treat cognitive decline in elderly people 14, 7.

Depression

Late-life depression is a common disorder sometimes occurring after acute illnesses, such as hip fracture or stroke 70, 71. Coexistence of symptoms of depression and low vitamin B6 status (plasma PLP level ≤20 nanomoles/liter) has been reported in a few cross-sectional studies 72, 73. In a prospective study of 3,503 free-living people aged 65 and older from the Chicago Health and Aging Project, total vitamin B6 intakes (but not dietary intakes alone) were inversely correlated with the incidence of depressive symptoms during a mean follow-up period of 7.2 years 74. In a randomized, double-blind, placebo-controlled trial in 563 individuals who suffered from a recent stroke, daily supplementation of 2 mg of folic acid, 0.5 mg of vitamin B12, and 25 mg of vitamin B6 halved the risk of developing a major depressive episode during a mean follow-up period of 7.1 years 75. This reduction in risk was associated with a 25% lower level of plasma homocysteine in supplemented patients compared to controls.

Additional evidence is needed to evaluate whether B vitamins could be included in the routine management of older people at high risk for depression 7.

Kidney stones

A large prospective study examined the relationship between vitamin B6 intake and the occurrence of symptomatic kidney stones in women. A group of more than 85,000 women without a prior history of kidney stones were followed over 14 years, and those who consumed 40 mg or more of vitamin B6 daily had only two-thirds the risk of developing kidney stones compared with those who consumed 3 mg or less 76. However, in a group of more than 45,000 men followed for 14 years, no association was found between vitamin B6 intake and the occurrence of kidney stones 77. Limited experimental data have suggested that supplementation with high doses of pyridoxamine may help decrease the formation of calcium oxalate kidney stones and reduce urinary oxalate levels, an important determinant of calcium oxalate kidney stone formation 78, 79. Presently, the relationship between vitamin B6 intake and the risk of developing kidney stones requires further study before any recommendations can be made.

Premenstrual syndrome (PMS)

Premenstrual syndrome (PMS) refers to a cluster of symptoms, including but not limited to fatigue, irritability, moodiness/depression, fluid retention, and breast tenderness, that begin sometime after ovulation (mid-cycle) and subside with the onset of menstruation (the monthly period). Some evidence suggests that vitamin B6 supplements could reduce the symptoms of premenstrual syndrome (PMS) such as moodiness, irritability, forgetfulness, bloating, and anxiety, but conclusions are limited due to the poor quality of most studies 80. A meta-analysis of nine published trials involving almost 1,000 women with PMS found that supplemental vitamin B6 up to 100 mg/day is more effective in reducing premenstrual syndrome symptoms than placebo, but most of the studies analyzed were small and several had methodological weaknesses 80. 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 81. The potential effectiveness of vitamin B6 in alleviating the mood-related symptoms of premenstrual syndrome could be due to its role as a cofactor in neurotransmitter biosynthesis 82. Although vitamin B6 shows promise for alleviating PMS symptoms, more research is needed before recommendations can be made 83.

Nausea and Vomiting in Pregnancy (morning sickness)

About half of all women experience “morning sickness” that consists of nausea and vomiting in the first few months of pregnancy, and about 50%–80% experience nausea only 84, 85. Morning sickness is not life threatening and typically goes away after 12–20 weeks, but its symptoms can disrupt a woman’s social and physical functioning 86.

Vitamin B6 has been used since the 1940s to treat nausea during pregnancy 7. Vitamin B6 was originally included in the medication Bendectin, which was prescribed for nausea and vomiting in pregnancy and later withdrawn from the market due to unproven concerns that it increased the risk for birth defects. The scientific literature includes isolated case reports of congenital defects in the infants of mothers who took pyridoxine supplements during the first half of pregnancy 14. Vitamin B6 itself is considered safe during pregnancy and has been used in pregnant women without any evidence of fetal harm 87. A more recent observational study found no association between pyridoxine supplementation (mean dose 132.3 ± 74 mg/day) in pregnant people starting at 7 weeks gestation and continuing for 9 ± 4.2 weeks and teratogenic effects in their infants 88.

Prospective studies on vitamin B6 supplements to treat morning sickness have had mixed results. In two randomized, placebo-controlled trials, including 401 pregnant women that used 25 mg of pyridoxine every eight hours for three days 89 or 10 mg of pyridoxine every eight hours for five days 90, suggested that vitamin B6 may be beneficial in reducing nausea in pregnant women who were experiencing nausea. 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 85.

It should be noted that nausea and vomiting in the first few months of pregnancy usually resolves without any treatment, making it difficult to perform well-controlled trials. More recently, nausea and vomiting in pregnancy symptoms were evaluated using Pregnancy Unique Quantification of Emesis (PUQE) scores in a randomized, double-blind, placebo-controlled study conducted in 256 pregnant women (7-14 weeks’ gestation) suffering from nausea and vomiting in pregnancy 91. Supplementation with pyridoxine and the drug doxylamine significantly improved morning sickness symptoms, as assessed by lower PUQE scores compared to placebo. Moreover, more women supplemented with pyridoxine-doxylamine (48.9%) than placebo-treated (32.8%) asked to continue their treatment at the end of the 15-day trial. Other randomized trials have shown that a combination of vitamin B6 and doxylamine (an antihistamine) is associated with a 70% reduction in nausea and vomiting in pregnant women and lower hospitalization rates for this problem 84, 92.

The American Congress of Obstetrics and Gynecology (ACOG) recommends monotherapy with 10–25 mg of vitamin B6 (pyridoxine hydrochloride) three or four times a day to treat nausea and vomiting in pregnancy 92. If the patient’s condition does not improve, American Congress of Obstetrics and Gynecology (ACOG) recommends adding doxylamine succinate (10 mg) 86. However, before taking a vitamin B6 supplement, pregnant women should consult a physician because doses could approach the Tolerable Upper Intake Level (the maximum daily intake unlikely to cause adverse health effects) 14.

Metabolic diseases

A few rare inborn metabolic disorders, including pyridoxine-dependent epilepsy and pyridoxamine 5′-phosphate oxidase deficiency, are the cause of early-onset epileptic encephalopathies that are found to be responsive to pharmacologic doses of vitamin B6. In individuals affected by pyridoxine-dependent epilepsy and pyridoxamine 5′-phosphate oxidase deficiency, PLP bioavailability is limited, and treatment with pyridoxine and/or PLP have been used to alleviate or abolish epileptic seizures characterizing these conditions 93, 94. Pyridoxine therapy, along with dietary protein restriction, is also used in the management of vitamin B6 responsive homocystinuria caused by the deficiency of the PLP-dependent enzyme, cystathionine beta-synthase 95.

Carpal tunnel syndrome

Carpal tunnel syndrome causes numbness, pain, and weakness of the hand and fingers due to compression of the median nerve at the wrist. It may result from repetitive stress injury of the wrist or from soft-tissue swelling, which sometimes occurs with pregnancy or hypothyroidism. Early studies by the same investigator suggested that supplementation with 100-200 mg/day of vitamin B6 for several months might improve carpal tunnel syndrome symptoms in individuals with low vitamin B6 status 96, 97. In addition, a cross-sectional study in 137 men not taking vitamin supplements found that decreased blood levels of PLP were associated with increased pain, tingling, and nocturnal awakening—all symptoms of carpal tunnel syndrome 98. However, studies using electrophysiological measurements of median nerve conduction have largely failed to find an association between vitamin B6 deficiency and carpal tunnel syndrome (86). While a few studies have noted some symptomatic relief with vitamin B6 supplementation, double-blind, placebo-controlled trials have not generally found vitamin B6 to be effective in treating carpal tunnel syndrome 99. Yet, despite its equivocal effectiveness, vitamin B6 supplementation is sometimes used in complementary therapy in an attempt to avoid hand surgery. Patients taking high doses of vitamin B6 should be advised by a physician and monitored for vitamin B6-related toxicity symptoms 100.

How much vitamin B6 do you need?

The amount of vitamin B6 you need depends on your age. Average daily recommended amounts are listed below in milligrams (mg). Intake recommendations for vitamin B6 and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Institute of Medicine 1. Dietary Reference Intake (DRI) is the general term for a set of reference values used for planning and assessing nutrient intakes of healthy people. These values, which vary by age and gender, include:

  • Recommended Dietary Allowance (RDA): Average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.
  • Adequate Intake (AI): Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA.
  • Estimated Average Requirement (EAR): Average daily level of intake estimated to meet the requirements of 50% of healthy individuals; usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them; can also be used to assess the nutrient intakes of individuals.
  • Tolerable Upper Intake Level (UL): Maximum daily intake unlikely to cause adverse health effects.

Table 1 lists the current Recommended Dietary Allowances (RDAs) for vitamin B6 1. For infants from birth to 12 months, the Institute of Medicine Food and Nutritional Board established an Adequate Intake (AI) for vitamin B6 that is equivalent to the mean intake of vitamin B6 in healthy, breastfed infants.

The Food and Nutrition Board has established Tolerable Upper Intake Level (the maximum daily intake unlikely to cause adverse health effects) for vitamin B6 that apply to both food and supplement intakes (Table 2) 1. The Food and Nutrition Board noted that although several reports show sensory neuropathy occurring at doses lower than 500 mg/day, studies in patients treated with vitamin B6 (average dose of 200 mg/day) for up to 5 years found no evidence of this effect 1. Based on limitations in the data on potential harms from long-term use, the Food and Nutrition Board halved the dose used in these studies to establish a Tolerable Upper Intake Level (UL) of 100 mg/day for adults. The Tolerable Upper Intake Level (ULs) are lower for children and adolescents based on body size. The Tolerable Upper Intake Level (ULs) do not apply to individuals receiving vitamin B6 for medical treatment, but such individuals should be under the care of a physician.

Table 1. Recommended Dietary Allowances (RDAs) for Vitamin B6

Life StageRecommended Amount
Birth to 6 months*0.1 mg
Infants 7–12 months*0.3 mg
Children 1–3 years0.5 mg
Children 4–8 years0.6 mg
Children 9–13 years1.0 mg
Teens 14–18 years (boys)1.3 mg
Teens 14–18 years (girls)1.2 mg
Adults 19–50 years1.3 mg
Adults 51+ years (men)1.7 mg
Adults 51+ years (women)1.5 mg
Pregnant teens and women1.9 mg
Breastfeeding teens and women2.0 mg

Footnote: *Adequate Intake (AI) = Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA.

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Table 2. Tolerable Upper Intake Levels (ULs) for Vitamin B6

AgeMaleFemalePregnancyLactation
Birth to 6 monthsNot possible to establish*Not possible to establish*
7–12 monthsNot possible to establish*Not possible to establish*
1–3 years30 mg30 mg
4–8 years40 mg40 mg
9–13 years60 mg60 mg
14–18 years80 mg80 mg80 mg80 mg
19+ years100 mg100 mg100 mg100 mg

Footnotes: *Breast milk, formula, and food should be the only sources of vitamin B6 for infants.

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Vitamin B6 Supplements

Vitamin B6 is available in multivitamins, in supplements containing other B complex vitamins, and as a stand-alone  supplement that contain only vitamin B6 101. The most common vitamin B6 vitamer in supplements is pyridoxine (in the form of pyridoxine hydrochloride [HCl]), although some supplements contain PLP 14.

Vitamin B6 supplements are available in oral capsules or tablets (including sublingual and chewable tablets) and liquids. Absorption of vitamin B6 from supplements is similar to that from food sources and does not differ substantially among the various forms of supplements 1. Although the body absorbs large pharmacological doses of vitamin B6 well, it quickly eliminates most of the vitamin in the urine 102.

About 28% to 36% of the general population uses supplements containing vitamin B6 103, 104. Adults aged 51 years or older and children younger than 9 are more likely than members of other age groups to take supplements containing vitamin B6 14.

Can vitamin B6 be harmful?

High intakes of vitamin B6 from food sources have not been reported to cause adverse effects 9. People almost never get too much vitamin B6 from food. But taking high levels of vitamin B6 from supplements for a year or longer can cause severe nerve damage, leading people to lose control of their bodily movements. The symptoms usually stop when they stop taking the supplements. Other symptoms of too much vitamin B6 include painful, unsightly skin patches, extreme sensitivity to sunlight, nausea, and heartburn.

vitamin b6 foods

What foods provide vitamin B6?

Vitamin B6 is found naturally in many foods and is added to other foods. You can get recommended amounts of vitamin B6 by eating a variety of foods, including the following 8:

  • Poultry, fish, and organ meats, all rich in vitamin B6.
  • Potatoes and other starchy vegetables, which are some of the major sources of vitamin B6 for Americans.
  • Fruit (other than citrus), which are also among the major sources of vitamin B6 for Americans.

Vitamin B6 is found in a wide variety of foods 1, 10, 105 and is added to other foods. The richest sources of vitamin B6 include fish, beef liver and other organ meats, potatoes and other starchy vegetables, and fruit (other than citrus).

In the United States, adults obtain most of their dietary vitamin B6 from fortified cereals, beef, poultry, starchy vegetables, and some non-citrus fruits 1, 10, 106. About 75% of vitamin B6 from a mixed diet is bioavailable 1.

The U.S. Department of Agriculture’s (USDA’s) FoodData website (https://fdc.nal.usda.gov) lists the nutrient content of many foods and provides a comprehensive list of foods containing vitamin B6 arranged by nutrient content (https://ods.od.nih.gov/pubs/usdandb/VitaminB6-Content.pdf) and by food name (https://ods.od.nih.gov/pubs/usdandb/VitaminB6-Food.pdf).

Table 3. Food Sources of Vitamin B6

FoodMilligrams (mg) per servingPercent Daily Value (DV)*
Chickpeas, canned, 1 cup1.165
Beef liver, pan fried, 3 ounces0.953
Tuna, yellowfin, fresh, cooked, 3 ounces0.953
Salmon, sockeye, cooked, 3 ounces0.635
Chicken breast, roasted, 3 ounces0.529
Breakfast cereals, fortified with 25% of the DV for vitamin B60.425
Potatoes, boiled, 1 cup0.425
Turkey, meat only, roasted, 3 ounces0.425
Banana, 1 medium0.425
Marinara (spaghetti) sauce, ready to serve, 1 cup0.425
Ground beef, patty, 85% lean, broiled, 3 ounces0.318
Waffles, plain, ready to heat, toasted, 1 waffle0.318
Bulgur, cooked, 1 cup0.212
Cottage cheese, 1% low-fat, 1 cup0.212
Squash, winter, baked, ½ cup0.212
Rice, white, long-grain, enriched, cooked, 1 cup0.16
Nuts, mixed, dry-roasted, 1 ounce0.16
Raisins, seedless, ½ cup0.16
Onions, chopped, ½ cup0.16
Spinach, frozen, chopped, boiled, ½ cup0.16
Tofu, raw, firm, prepared with calcium sulfate, ½ cup0.16
Watermelon, raw, 1 cup0.16

Footnote: *DV = Daily Value. The U.S. Food and Drug Administration (FDA) developed Daily Values (DVs) to help consumers compare the nutrient contents of foods and dietary supplements within the context of a total diet. The Daily Value (DV) for vitamin B6 is 1.7 mg for adults and children age 4 years and older 107. FDA does not require food labels to list vitamin B6 content unless vitamin B6 has been added to the food. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet.

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Am I getting enough vitamin B6?

Most children, adolescents, and adults in the United States consume the recommended amounts of vitamin B6 from the foods they eat, according to an analysis of data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES) 103. The average vitamin B6 intake is about 1.5 mg/day in women and 2 mg/day in men 1.

However, 11% of vitamin B6 supplement users and 24% of people in the United States who do not take supplements containing vitamin B6 have low plasma pyridoxal 5’ phosphate (PLP) concentrations (less than 20 nmol/L) 103. In the 2003–2004 National Health and Nutrition Examination Survey (NHANES) analysis, plasma pyridoxal 5’ phosphate (PLP) concentrations were low even in some groups that took 2.0–2.9 mg/day, which is higher than the current Recommended Dietary Allowance (RDA). Among supplement users and nonusers, plasma pyridoxal 5’ phosphate (PLP) levels were much lower in women than men, non-Hispanic blacks than non-Hispanic whites, current smokers than never smokers, and people who were underweight than those of normal weight. Teenagers had the lowest vitamin B6 concentrations, followed by adults aged 21–44 years. However, plasma pyridoxal 5’ phosphate (PLP) levels in the elderly were not particularly low, even in those who did not use supplements. Based on these data, the authors of this analysis concluded that the current Recommended Dietary Allowances (RDAs) might not guarantee adequate vitamin B6 status in many population groups 103.

Most people in the United States get enough vitamin B6 from the foods they eat. However, these groups of people are more likely than others to have trouble getting enough vitamin B6 8:

  • People whose kidneys do not work properly, including people who are on kidney dialysis and those who have had a kidney transplant.
  • People with autoimmune disorders, which cause their immune system to mistakenly attack their own healthy tissues. For example, people with rheumatoid arthritis, celiac disease, Crohn’s disease, ulcerative colitis, or inflammatory bowel disease sometimes have low vitamin B6 levels.
  • People with alcohol dependence.

What happens if I don’t get enough vitamin B6?

Vitamin B6 deficiency is uncommon in the United States 8. People who don’t get enough vitamin B6 can have a range of symptoms, including anemia, itchy rashes, scaly skin on the lips, cracks at the corners of the mouth, and a swollen tongue. Other symptoms of very low vitamin B6 levels include depression, confusion, and a weak immune system. Infants who do not get enough vitamin B6 can become irritable or develop extremely sensitive hearing or seizures.

Vitamin B6 Deficiency

Isolated vitamin B6 deficiency, also known as pyridoxine deficiency, is very rare in the United States; inadequate vitamin B6 status is usually associated with low concentrations of other B-complex vitamins, such as vitamin B12 and folic acid 108, 2, 109. Vitamin B6 deficiency causes biochemical changes that become more obvious as the deficiency progresses 2, 110. Vitamin B6 deficiency is associated with microcytic anemia, peripheral neuropathy, mental status changes, electroencephalographic abnormalities, seborrhoeic dermatitis, angular cheilitis (scaling on the lips and cracks at the corners of the mouth) and glossitis (inflammation of the tongue), depression and confusion, and weakened immune function 108, 1, 2, 111. Individuals with borderline vitamin B6 concentrations or mild deficiency might have no deficiency signs or symptoms for months or even years. Fetal brain development requires adequate vitamin B6, and this continues throughout infancy. In infants, vitamin B6 deficiency causes irritability, abnormally acute hearing, and convulsive seizures 2, 112.

Vitamin B6 is one of the vital micronutrients involved in one-carbon metabolism along with folate and vitamin B12 113. Pyridoxal 5-phosphate (PLP), the active form of vitamin B6, acts as a cofactor in more than 100 enzymatic reactions in carbohydrate, amino acids and lipid metabolism 114 . It has also been shown to have antioxidant 115, anti-inflammatory properties 116, cognitive functions 117, 63, 64, 65 and a role in the immune response 118, 119.

Vitamin B6 deficiency is uncommon in the United States 8. Most people in the United States get enough vitamin B6 from the foods they eat 120, 103. However, these groups of people are more likely than others to have trouble getting enough vitamin B6 8, 108:

  • People whose kidneys do not work properly, including people who are on kidney dialysis (hemodialysis or peritoneal dialysis) and those who have had a kidney transplant.
  • People with autoimmune disorders, which cause their immune system to mistakenly attack their own healthy tissues. For example, people with rheumatoid arthritis, celiac disease, Crohn’s disease, ulcerative colitis, or inflammatory bowel disease sometimes have low vitamin B6 levels.
  • People with protein-energy malnutrition.
  • States of decreased consumption and/or absorption. For example, pregnancy, chronic alcohol dependence and post-weight loss surgery.

End-stage renal diseases, chronic renal insufficiency, and other kidney diseases can cause vitamin B6 deficiency 10. In addition, vitamin B6 deficiency can result from malabsorption syndromes, such as celiac disease, Crohn’s disease, and ulcerative colitis. Certain genetic diseases, such as homocystinuria, can also cause vitamin B6 deficiency 2. Some medications, such as antiepileptic drugs, can lead to vitamin B6 deficiency over time.

Vitamin B6 concentrations can be measured directly by assessing concentrations of pyridoxal 5’ phosphate (PLP); other vitamers; or total vitamin B6 in plasma, red blood cells, or urine 9. Vitamin B6 concentrations can also be measured indirectly by assessing either red blood cell aminotransferase saturation by pyridoxal 5’ phosphate (PLP) or tryptophan metabolites. Plasma pyridoxal 5’ phosphate (PLP) is the most common measure of vitamin B6 status 14.

Pyridoxal 5’ phosphate (PLP) concentrations of more than 30 nanomole per liter [nmol/L] have been traditional indicators of adequate vitamin B6 status in adults 10. However, the Food and Nutrition Board at the Institute of Medicine of the National Academies used a plasma pyridoxal 5’ phosphate (PLP) level of 20 nmol/L as the major indicator of adequacy to calculate the Recommended Dietary Allowances (RDAs) for adults 9, 10. Plasma Pyridoxal 5’ phosphate (PLP) of less than 20 nmol/L is considered vitamin B6 deficiency 121.

Vitamin B6 deficiency causes

Dietary vitamin B6 deficiency, though rare, can develop because extensive processing can deplete foods of vitamin B6. In the United States and other western cultures, vitamin B6 deficiency is rare due to adequate diets, including vitamin B6 sources from fish, organ meats, poultry, potatoes, grains, legumes, and non-citrus fruits.

Isolated B6 deficiency is rare and is usually found in association with other B vitamin deficiencies such as folic acid and B12.

Secondary vitamin B6 deficiency or pyridoxine deficiency most often results from 122, 108:

  • Vitamin B6 or Pyridoxine intake is reduced in cases of severe malnutrition.
  • Protein-energy malnutrition
  • Malabsorption states such as celiac disease, inflammatory bowel disease (Crohn’s disease, and ulcerative colitis), and post weight loss surgery
  • Vitamin B6 or Pyridoxine absorption is reduced in elderly persons and in patients with intestinal disease or who have undergone surgery.
  • Chronic alcohol dependence
  • Autoimmune diseases, such as rheumatoid arthritis, have increased breakdown and metabolic requirements of vitamin B6, resulting in higher demand for dietary supplementation of vitamin B6.
  • Pyridoxine clearance is enhanced by liver disorders, such as hepatitis, and by several medications.
  • Pyridoxine breakdown is enhanced in conditions associated with increased alkaline phosphatase levels.
  • Use of pyridoxine-inactivating drugs (eg, anticonvulsants, isoniazid, cycloserine, levodopa, hydralazine, corticosteroids, penicillamine) 123, 124, 125, 126
  • Excessive loss during hemodialysis and the patient who have undergone kidney transplants are more at risk of vitamin B6 deficiency. Patients with chronic renal failure, especially those receiving hemodialysis or peritoneal dialysis, have low plasma levels of vitamin B6 and usually respond well to oral or parenteral vitamin B6 therapy 127, 128.
  • Pregnancy – Pregnancy can cause a pyridoxine-deficient state; however, a change in the ratio of plasma PLP to pyridoxal does occur, thereby falsely suggesting a deficiency state if only serum PLP is measured.

Rarely, secondary deficiency results from increased metabolic demand (eg, in hyperthyroidism).

Rare inborn errors of metabolism can affect pyridoxine metabolism.

Risk factors for developing vitamin B6 deficiency

Several factors contribute to an increased risk for vitamin B6 deficiency or pyridoxine deficiency 129:

  • Advanced age
  • Medical conditions that may increase the risk for vitamin B6 deficiency or pyridoxine deficiency include the following:
    • Severe malnutrition
    • Sickle cell disease
    • Inflammatory conditions 130, 131
    • Rheumatoid arthritis 130
    • Hospitalization
    • Celiac disease
    • Hepatitis and extrahepatic biliary obstruction
    • Hepatocellular carcinoma
    • Chronic renal failure
    • Kidney transplant 132
    • Hyperoxaluria types 1 and 2
    • High serum alkaline phosphatase level, such as in cirrhosis and tissue injury
    • Catabolic state
  • Medical procedures that may increase the risk for vitamin B6 deficiency or pyridoxine deficiency include the following:
    • Hemodialysis
    • Peritoneal dialysis
    • Phototherapy for hyperbilirubinemia
  • Medications that may increase the risk for vitamin B6 deficiency or pyridoxine deficiency include the following:
    • Cycloserine
    • Hydralazine
    • Isoniazid
    • D-penicillamine
    • Pyrazinamide
  • Social-behavioral conditions that may increase the risk for vitamin B6 deficiency or pyridoxine deficiency include the following:
    • Excessive alcohol ingestion (except for pyridoxine-supplemented beer)
    • Tobacco smoking
    • Severe malnutrition
  • Other risk factors that may increase the risk for pyridoxine deficiency include the following:
    • Poisoning, such as Gyromitra mushroom poisoning
    • Perinatal factors, such as a pyridoxine-deficient mother
    • Inherited conditions, such as pyridoxine-dependent neonatal seizures 133, 134, 135

Groups at Risk of vitamin B6 deficiency

Frank vitamin B6 deficiencies are relatively rare in the United States but some individuals might have marginal vitamin B6 status 2. The following groups are among those most likely to have inadequate intakes of vitamin B6.

Individuals with impaired kidney function

People with poor kidney function, including those with end-stage renal disease (also called end-stage kidney disease or kidney failure) and chronic renal insufficiency, often have low vitamin B6 concentrations 10. Plasma pyridoxal 5’ phosphate (PLP) concentrations are also low in patients receiving maintenance kidney dialysis or intermittent peritoneal dialysis, as well as those who have undergone a kidney transplant, perhaps due to increased metabolic clearance of pyridoxal 5’ phosphate (PLP) 136. Patients with kidney disease often show clinical symptoms similar to those of people with vitamin B6 deficiency 136.

Individuals with Autoimmune Disorders

People with rheumatoid arthritis often have low vitamin B6 concentrations, and vitamin B6 concentrations tend to decrease with increased disease severity 10. These low vitamin B6 levels are due to the inflammation caused by the disease and, in turn, increase the inflammation associated with the disease. Although vitamin B6 supplements can normalize vitamin B6 concentrations in patients with rheumatoid arthritis, they do not suppress the production of inflammatory cytokines or decrease levels of inflammatory markers 10, 137.

Patients with celiac disease, Crohn’s disease, ulcerative colitis, inflammatory bowel disease, and other malabsorptive autoimmune disorders tend to have low plasma pyridoxal 5’ phosphate (PLP) concentrations 10. The mechanisms for this effect are not known. However, celiac disease is associated with lower pyridoxine absorption, and low PLP concentrations in inflammatory bowel disease could be due to the inflammatory response 10.

People with Alcohol Dependence

Plasma pyridoxal 5’ phosphate (PLP) concentrations tend to be very low in people with alcohol dependence 1. Alcohol produces acetaldehyde, which decreases net pyridoxal 5’ phosphate (PLP) formation by cells and competes with Pyridoxal 5’ phosphate in protein binding 1. As a result, the PLP in cells might be more susceptible to hydrolysis by membrane-bound phosphatase. People with alcohol dependence might benefit from pyridoxine supplementation 10.

Vitamin B6 deficiency prevention

The human body cannot store vitamin B6, and therefore a daily source is required. However, in the United States isolated vitamin B6 deficiency is rare, because most children, adolescents, and adults in the United States consume the recommended amounts of vitamin B6, according to an analysis of data from the 2003–2004 National Health and Nutrition Examination Survey 103. The average vitamin B6 intake is about 1.5 mg/day in women and 2 mg/day in men 1.

Vitamin B6 (Pyridoxine) supplementation is indicated in cases of vitamin B6 deficiency, which may be due to poor kidney function, autoimmune diseases, increased alcohol intake (chronic alcohol use), or in people who take these medications: isoniazid, cycloserine, valproic acid, phenytoin, carbamazepine, primidone, hydralazine, and theophylline 138, 139, 140, 141, 18, 142, 143.

Vitamin B6 deficiency is usually found in association with other B vitamin deficiencies such as folic acid and B12. So these B vitamin supplements are also needed.

There is evidence to suggest reduced bioavailability 144 as well as digestibility 145 of vitamin B6 from plant foods compared to animal foods. This may be important to those who favor a plant-based diet exclusively (i.e., vegans and vegetarians) 146. These individuals may need vitamin B6 supplementation. The major vitamin B6 supplement in multivitamins is pyridoxine hydrochloride.

Prophylactic administration of vitamin B6 (Pyridoxine) should be provided when a patient is using certain medications, such as isoniazid (30-450 mg/day, which may be based gram for gram) and penicillamine (100 mg/day) 147.

Estrogen-induced reduction in tryptophan metabolism may require vitamin B6 (Pyridoxine) supplementation of 20-25 mg/day 147.

Vitamin B6 Deficiency signs and symptoms

Signs and symptoms of vitamin B6 deficiency or pyridoxine deficiency include the following 148, 149, 150 :

  • General symptoms – Weakness, dizziness
  • Oral signs and symptoms – Glossitis (inflammation of the tongue), angular cheilitis (scaling on the lips and cracks at the corners of the mouth)
  • Dermatologic signs and symptoms – Seborrheic dermatitis
  • Neurologic symptoms in adults – Distal limb numbness and weakness, impaired vibration and proprioception, sensory ataxia, generalized seizures
  • Neurologic symptoms in neonates and young infants – Hypotonia; irritability; restlessness; focal, bilateral motor, or myoclonic seizures; infantile spasms

Vitamin B6 deficiency in adults causes peripheral neuropathy and a pellagra-like syndrome, with seborrheic dermatitis, glossitis, and angular cheilitis. Additional clinical findings of vitamin B6 deficiency may include mental status changes, depression, confusion, EEG abnormalities, seizures and normocytic, microcytic, or sideroblastic anemia 151.

Rarely, vitamin B6 deficiency may present with seizures in infants 152, 153. Seizures, particularly in infants, may be refractory to treatment with anticonvulsants.

Current studies are evaluating the role of B6 deficiency in heart disease, cancer, attention deficit hyperactivity disorders (ADHD) and cognitive decline as medical conditions that may respond to supplementation 109, 7, 14. To date, there is no clear evidence to support vitamin B6 supplement use beyond the normal dietary intake. However, some studies indicate a reduction of symptoms in the premenstrual syndrome (PMS) with supplementation of vitamin B6, particularly a decrease in moodiness, irritability, and forgetfulness 7, 14. The American College of Obstetrics and Gynecology recommend vitamin B6 supplementation (1.9 mg per day) for hyperemesis gravidarum (severe nausea and vomiting during pregnancy) 154.

Figure 5. Glossitis

Glossitis

Figure 6. Angular cheilitis

Angular cheilitis

Figure 7.  Seborrheic dermatitis

Seborrheic dermatitis

Vitamin B6 Deficiency diagnosis

Diagnosis of vitamin B6 deficiency is usually clinical. There is no single accepted laboratory test of vitamin B6 status; measurement of serum pyridoxal phosphate is most common. Plasma Pyridoxal 5’ phosphate (PLP) of less than 20 nmol/L is considered vitamin B6 deficiency 121.

Early or subclinical vitamin B6 deficiency may have vague or fleeting symptoms; however, new-onset sensory polyneuropathy, altered mental status, dermatitis in adults, or seizures in infancy should raise clinical suspicion of a clinically significant B6 deficiency 108.

Vitamin B6 deficiency should be considered in 108:

  • Any infant who has seizures
  • Any patient who has seizures refractory to treatment with anticonvulsants
  • Any patient with deficiencies of other B vitamins, particularly in patients with alcoholism or protein-energy undernutrition

Testing for vitamin B6 can be difficult in real-time in many clinical scenarios. Direct biomarkers B6 vitamers in serum, plasma, red blood cell, and urine are used. Serum measurement of the active vitamin pyridoxal 5′-phosphate (PLP) form is available in some clinical settings. However, the assay is not widely available or timely 108. Serum or urinary 4-Pyridoxic acid (4PA) is the end product of vitamin B6 catabolism, is an indicator of recent vitamin B6 intake. A clinical alternative is an indirect measurement technique of vitamin B6, which includes measuring urinary excretion of xanthurenic acid (an amino acid catabolite of tryptophan) following a measured bolus of tryptophan 108. Increased levels of xanthurenic acid may indicate inadequate active B6 for the formation of the amino acid tryptophan 155. Urinary excretion of xanthurenic acid is usually less than 65 mmol/day following a 2 g tryptophan load. Excretion of xanthurenic acid above this threshold suggests abnormal tryptophan metabolism due to vitamin B6 insufficiency.

Red blood cell transaminase activity, with and without pyridoxal 5′-phosphate (PLP) added, has been used as a functional test of pyridoxine status and maybe a more accurate reflection of vitamin B6 status in critically ill patients 156. Urinary 4-pyridoxic acid excretion greater than 3.0 mmol/day can be used as an indicator of adequate short-term vitamin B6 status (this is often reported as “urinary pyridoxic acid”) 108.

Vitamin B6 Deficiency treatment

In vitamin B6-deficient states and illnesses, treatment dosage is variable and depends on the severity of symptoms 108. Vitamin B6 (Pyridoxine) is available therapeutically in both oral and parenteral formulations. Neonates with vitamin B6 deficiency seizures may require 10 to 100 mg intravenous (IV) Pyridoxine for effective treatment of active seizures. Less serious or less acute presentations can be supplemented with Pyridoxine doses ranging from 25 mg to 600 mg per day orally depending on symptom complex.

Levels of pyridoxine hydrochloride supplementation in various medical conditions are as follows 157:

  • Cirrhosis – 50 mg/d
  • Hemodialysis – 5-50 mg/d
  • Peritoneal dialysis – 2.5-5 mg/d
  • Chronic renal failure – 2.5-5 mg/d
  • Sideroblastic anemia – 50-600 mg/d
  • Pyridoxine-dependent seizures – 100 mg/d
  • Homocystinuria – 100-500 mg/d
  • Homocystinemia – 100-500 mg/d
  • Gyromitra poisoning – 25 mg/kg IV

At one time, pyridoxine supplementation was given to people with sickle cell anemia; however, no changes were noted in these patients’ hematologic indexes or disease activity.

Importantly, vitamin B6 or Pyridoxine therapy can be life-saving in refractory Isoniazid (a potent antibiotic used in the treatment of tuberculosis) overdose-induced seizures 108. The vitamin B6 (Pyridoxine) dose is equal to the known amount of Isoniazid (INH) ingested or a maximum of 5,000 mg and is dosed 1,000 to 4,000 mg IV as the first dose, then 1,000 mg IM or IV every 30 minutes 158. In ethylene glycol overdose, vitamin B6 is recommended at 50 to 100 mg IV every 6 hours to facilitate shunting the metabolism of ethylene glycol to nontoxic pathways leading to glycine (nontoxic) instead of toxic pathways leading to toxic metabolites such as formate.

Additional, less common uses are in hydralazine overdose, where the recommended dose of vitamin B6 is 25 mg/kg, the first third administered intramuscularly, and the remainder as a 3-hour IV infusion. Gyromitra (mushroom) toxicity treatment is at 25 mg/kg infused IV over 30 min 108.

Hyperemesis gravidarum (severe nausea and vomiting during pregnancy) may respond to vitamin B6 at a dosage of 25 mg orally every 8 hours.

Vitamin B6 Deficiency prognosis

If diagnosed appropriately, vitamin B6 deficiency is effectively treated with adequate oral or parenteral vitamin B6 (pyridoxine) supplementation.

Care should be taken when supplementing pyridoxine, because high pyridoxine states can cause peripheral neuropathy characterized by ataxia and burning pain in the feet, beginning approximately 1 month to 3 years following supplementation 159. Although this usually occurs at very high supplementation doses, complications have been reported with doses as low as 50 mg/day 159.

Care should also be taken when prescribing pyridoxine supplementation to postpartum women who are breastfeeding, because high doses of pyridoxine can cause hypocalcaemia (low blood calcium) 159. A cohort study of postmenopausal women found that a high intake of pyridoxine, coupled with a high intake of vitamin B12, is linked to an increased risk of hip fracture. Compared with women who consumed less than 2 mg/d of total pyridoxine, those whose intake was 35 mg/d or higher had an elevated fracture risk 160.

Injecting pyridoxine into an infant or neonate can cause a precipitous decrease in blood pressure.

Pyridoxine has the highest adverse outcome per toxic exposure for any vitamin, although no deaths have been reported.

Vitamin B6 Side Effects and Toxicity

Because adverse effects have only been documented from vitamin B6 supplements and never from food sources, safety concerning only the supplemental form of vitamin B6 (pyridoxine) is discussed. The ingestion of megadoses (> 500 mg/day) of vitamin B6 or pyridoxine (eg, taken to treat carpal tunnel syndrome or premenstrual syndrome although efficacy is unproven) may cause painful neurological symptoms known as sensory neuropathy with deficits in a stocking-glove distribution, including progressive sensory ataxia and severe impairment of position and vibration senses 151. Symptoms include pain and numbness of the extremities and in severe cases, difficulty walking 7. Senses of touch, temperature, and pain are less affected. Motor and central nervous systems are usually intact.

Sensory neuropathy typically develops at doses of pyridoxine in excess of 1,000 mg per day. However, there have been a few case reports of individuals who developed sensory neuropathies at doses of less than 500 mg daily over a period of months 7. Yet, none of the studies in which an objective neurological examination was performed reported evidence of sensory nerve damage at intakes below 200 mg pyridoxine daily 161.

However, chronic administration of 1–6 g oral pyridoxine per day for 12–40 months can cause severe and progressive sensory neuropathy characterized by ataxia (loss of control of bodily movements) 162, 163, 164, 165, 161. Symptom severity appears to be dose dependent, and the symptoms usually stop if the patient discontinues the pyridoxine supplements as soon as the neurologic symptoms appear. Other effects of excessive vitamin B6 intakes include painful, disfiguring dermatological lesions; photosensitivity; and gastrointestinal symptoms, such as nausea and heartburn 1, 163, 164, 2.

The scientific literature includes isolated case reports of congenital defects in the infants of individuals who took pyridoxine supplements during the first half of pregnancy 14. However, a more recent observational study found no association between pyridoxine supplementation (mean dose 132.3 ± 74 mg/day) in pregnant people starting at 7 weeks gestation and continuing for 9 ± 4.2 weeks and teratogenic effects in their infants 88.

To prevent sensory neuropathy in virtually all individuals, the Food and Nutrition Board of the Institute of Medicine set the tolerable upper intake level (UL) for pyridoxine at 100 mg/day for adults (Table 2) 9. Because placebo-controlled studies have generally failed to show therapeutic benefits of high doses of pyridoxine, there is little reason to exceed the tolerable upper intake level (UL) of 100 mg/day. The Tolerable Upper Intake Level (ULs) do not apply to individuals receiving vitamin B6 for medical treatment, but such individuals should be under the care of a physician.

  • Diagnosis of vitamin B6 toxicity is clinical.
  • Treatment of vitamin B6 toxicity is to stop taking vitamin B6. Recovery is slow and, for some patients, incomplete.
References
  1. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998. https://www.nap.edu/catalog/6015/dietary-reference-intakes-for-thiamin-riboflavin-niacin-vitamin-b6-folate-vitamin-b12-pantothenic-acid-biotin-and-choline
  2. McCormick D. Vitamin B6. In: Bowman B, Russell R, eds. Present Knowledge in Nutrition. 9th ed. Washington, DC: International Life Sciences Institute; 2006.
  3. Dakshinamurti S, Dakshinamurti K. Vitamin B6. In: Zempleni J, Rucker RB, McCormick DB, Suttie JW, eds. Handbook of Vitamins. 4th ed. New York: CRC Press (Taylor & Fracis Group); 2007:315-359.
  4. McCormick DB. Vitamin B6. In: Bowman BA, Russell RM, eds. Present Knowledge in Nutrition. Vol. I. Washington, D.C.: International Life Sciences Institute; 2006:269-277.
  5. Galluzzi L, Vacchelli E, Michels J, Garcia P, Kepp O, Senovilla L, Vitale I, Kroemer G. Effects of vitamin B6 metabolism on oncogenesis, tumor progression and therapeutic responses. Oncogene. 2013 Oct 17;32(42):4995-5004. doi: 10.1038/onc.2012.623
  6. di Salvo ML, Contestabile R, Safo MK. Vitamin B(6) salvage enzymes: mechanism, structure and regulation. Biochim Biophys Acta. 2011 Nov;1814(11):1597-608. doi: 10.1016/j.bbapap.2010.12.006
  7. Vitamin B6. https://lpi.oregonstate.edu/mic/vitamins/vitamin-B6
  8. Vitamin B6. https://ods.od.nih.gov/factsheets/VitaminB6-Consumer
  9. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998. https://nap.nationalacademies.org/read/6015/chapter/1
  10. Mackey A, Davis S, Gregory J. Vitamin B6. In: Shils M, Shike M, Ross A, Caballero B, Cousins R, eds. Modern Nutrition in Health and Disease. 10th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2005.
  11. Wilson, MP, Plecko, B, Mills, PB, Clayton, PT. Disorders affecting vitamin B6 metabolism. J Inherit Metab Dis. 2019; 42: 629– 646. https://doi.org/10.1002/jimd.12060
  12. Magnúsdóttir S, Ravcheev D, de Crécy-Lagard V, Thiele I. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Front Genet. 2015 Apr 20;6:148. doi: 10.3389/fgene.2015.00148
  13. COURSIN DB. Convulsive seizures in infants with pyridoxine-deficient diet. J Am Med Assoc. 1954 Jan 30;154(5):406-8. doi: 10.1001/jama.1954.02940390030009
  14. Vitamin B6. https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional
  15. Da Silva VR, Russell KA, Gregory JF 3rd. Vitamin B6. In: Erdman JW Jr., Macdonald IA, Zeisel SH. Present Knowldege in Nutrition. 10th ed: Wiley-Blackwell; 2012:307-320.
  16. Eliot AC, Kirsch JF. Pyridoxal phosphate enzymes: mechanistic, structural, and evolutionary considerations. Annu Rev Biochem. 2004;73:383-415. doi: 10.1146/annurev.biochem.73.011303.074021
  17. Leklem JE. Vitamin B-6. In: Shils M, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore: Williams & Wilkins; 1999:413-422.
  18. Clayton PT. B6-responsive disorders: a model of vitamin dependency. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):317-26. doi: 10.1007/s10545-005-0243-2
  19. Schnackerz KD, Benesch RE, Kwong S, Benesch R, Helmreich EJ. Specific receptor sites for pyridoxal 5′-phosphate and pyridoxal 5′-deoxymethylenephosphonate at the alpha and beta NH2-terminal regions of hemoglobin. J Biol Chem. 1983 Jan 25;258(2):872-5.
  20. Rios-Avila L, Nijhout HF, Reed MC, Sitren HS, Gregory JF 3rd. A mathematical model of tryptophan metabolism via the kynurenine pathway provides insights into the effects of vitamin B-6 deficiency, tryptophan loading, and induction of tryptophan 2,3-dioxygenase on tryptophan metabolites. J Nutr. 2013 Sep;143(9):1509-19. doi: 10.3945/jn.113.174599
  21. Oxenkrug G. Insulin resistance and dysregulation of tryptophan-kynurenine and kynurenine-nicotinamide adenine dinucleotide metabolic pathways. Mol Neurobiol. 2013 Oct;48(2):294-301. doi: 10.1007/s12035-013-8497-4
  22. Huq MD, Tsai NP, Lin YP, Higgins L, Wei LN. Vitamin B6 conjugation to nuclear corepressor RIP140 and its role in gene regulation. Nat Chem Biol. 2007 Mar;3(3):161-5. doi: 10.1038/nchembio861
  23. Ebbing M, Bønaa KH, Arnesen E, Ueland PM, Nordrehaug JE, Rasmussen K, Njølstad I, Nilsen DW, Refsum H, Tverdal A, Vollset SE, Schirmer H, Bleie Ø, Steigen T, Midttun Ø, Fredriksen A, Pedersen ER, Nygård O. Combined analyses and extended follow-up of two randomized controlled homocysteine-lowering B-vitamin trials. J Intern Med. 2010 Oct;268(4):367-82. doi: 10.1111/j.1365-2796.2010.02259.x
  24. Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E; Heart Outcomes Prevention Evaluation 2 Investigators. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke. 2009 Apr;40(4):1365-72. doi: 10.1161/STROKEAHA.108.529503
  25. Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, Hennekens C, Stampfer MJ. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA. 1998 Feb 4;279(5):359-64. doi: 10.1001/jama.279.5.359
  26. Ishihara J, Iso H, Inoue M, Iwasaki M, Okada K, Kita Y, Kokubo Y, Okayama A, Tsugane S; JPHC Study Group. Intake of folate, vitamin B6 and vitamin B12 and the risk of CHD: the Japan Public Health Center-Based Prospective Study Cohort I. J Am Coll Nutr. 2008 Feb;27(1):127-36. doi: 10.1080/07315724.2008.10719684
  27. Folsom AR, Nieto FJ, McGovern PG, Tsai MY, Malinow MR, Eckfeldt JH, Hess DL, Davis CE. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 1998 Jul 21;98(3):204-10. doi: 10.1161/01.cir.98.3.204
  28. Robinson K, Arheart K, Refsum H, Brattström L, Boers G, Ueland P, Rubba P, Palma-Reis R, Meleady R, Daly L, Witteman J, Graham I. Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. European COMAC Group. Circulation. 1998 Feb 10;97(5):437-43. doi: 10.1161/01.cir.97.5.437. Erratum in: Circulation 1999 Feb 23;99(7):983
  29. Robinson K, Mayer EL, Miller DP, Green R, van Lente F, Gupta A, Kottke-Marchant K, Savon SR, Selhub J, Nissen SE, et al. Hyperhomocysteinemia and low pyridoxal phosphate. Common and independent reversible risk factors for coronary artery disease. Circulation. 1995 Nov 15;92(10):2825-30. doi: 10.1161/01.cir.92.10.2825
  30. Lin PT, Cheng CH, Liaw YP, Lee BJ, Lee TW, Huang YC. Low pyridoxal 5′-phosphate is associated with increased risk of coronary artery disease. Nutrition. 2006 Nov-Dec;22(11-12):1146-51. doi: 10.1016/j.nut.2006.08.013
  31. Page JH, Ma J, Chiuve SE, Stampfer MJ, Selhub J, Manson JE, Rimm EB. Plasma vitamin B(6) and risk of myocardial infarction in women. Circulation. 2009 Aug 25;120(8):649-55. doi: 10.1161/CIRCULATIONAHA.108.809038
  32. Gerhard GT, Duell PB. Homocysteine and atherosclerosis. Curr Opin Lipidol. 1999 Oct;10(5):417-28. doi: 10.1097/00041433-199910000-00006
  33. Maron BA, Loscalzo J. Homocysteine. Clin Lab Med. 2006 Sep;26(3):591-609, vi. doi: 10.1016/j.cll.2006.06.008
  34. Kaplan P, Tatarkova Z, Sivonova MK, Racay P, Lehotsky J. Homocysteine and Mitochondria in Cardiovascular and Cerebrovascular Systems. Int J Mol Sci. 2020 Oct 18;21(20):7698. doi: 10.3390/ijms21207698
  35. Hermann A, Sitdikova G. Homocysteine: Biochemistry, Molecular Biology and Role in Disease. Biomolecules. 2021 May 15;11(5):737. doi: 10.3390/biom11050737
  36. Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ, Delport R, Potgieter HC. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr. 1994 Oct;124(10):1927-33. doi: 10.1093/jn/124.10.1927
  37. Lamers Y, Coats B, Ralat M, Quinlivan EP, Stacpoole PW, Gregory JF 3rd. Moderate vitamin B-6 restriction does not alter postprandial methionine cycle rates of remethylation, transmethylation, and total transsulfuration but increases the fractional synthesis rate of cystathionine in healthy young men and women. J Nutr. 2011 May;141(5):835-42. doi: 10.3945/jn.110.134197
  38. Huang T, Chen Y, Yang B, Yang J, Wahlqvist ML, Li D. Meta-analysis of B vitamin supplementation on plasma homocysteine, cardiovascular and all-cause mortality. Clin Nutr. 2012 Aug;31(4):448-54. doi: 10.1016/j.clnu.2011.01.003
  39. Bosy-Westphal A, Holzapfel A, Czech N, Müller MJ. Plasma folate but not vitamin B(12) or homocysteine concentrations are reduced after short-term vitamin B(6) supplementation. Ann Nutr Metab. 2001;45(6):255-8. doi: 10.1159/000046735
  40. Lee BJ, Huang MC, Chung LJ, Cheng CH, Lin KL, Su KH, Huang YC. Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease. Eur J Clin Nutr. 2004 Mar;58(3):481-7. doi: 10.1038/sj.ejcn.1601834
  41. Bostom AG, Carpenter MA, Kusek JW, Levey AS, Hunsicker L, Pfeffer MA, Selhub J, Jacques PF, Cole E, Gravens-Mueller L, House AA, Kew C, McKenney JL, Pacheco-Silva A, Pesavento T, Pirsch J, Smith S, Solomon S, Weir M. Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial. Circulation. 2011 Apr 26;123(16):1763-70. doi: 10.1161/CIRCULATIONAHA.110.000588
  42. Qin X, Huo Y, Xie D, Hou F, Xu X, Wang X. Homocysteine-lowering therapy with folic acid is effective in cardiovascular disease prevention in patients with kidney disease: a meta-analysis of randomized controlled trials. Clin Nutr. 2013 Oct;32(5):722-7. doi: 10.1016/j.clnu.2012.12.009
  43. Clarke R, Halsey J, Bennett D, Lewington S. Homocysteine and vascular disease: review of published results of the homocysteine-lowering trials. J Inherit Metab Dis. 2011 Feb;34(1):83-91. doi: 10.1007/s10545-010-9235-y
  44. Martí-Carvajal AJ, Solà I, Lathyris D, Karakitsiou DE, Simancas-Racines D. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2013 Jan 31;(1):CD006612. doi: 10.1002/14651858.CD006612.pub3. Update in: Cochrane Database Syst Rev. 2015;1:CD006612
  45. Zhang C, Chi FL, Xie TH, Zhou YH. Effect of B-vitamin supplementation on stroke: a meta-analysis of randomized controlled trials. PLoS One. 2013 Nov 25;8(11):e81577. doi: 10.1371/journal.pone.0081577
  46. Potter K, Hankey GJ, Green DJ, Eikelboom J, Jamrozik K, Arnolda LF. The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis. BMC Cardiovasc Disord. 2008 Sep 20;8:24. doi: 10.1186/1471-2261-8-24
  47. Løland KH, Bleie O, Blix AJ, Strand E, Ueland PM, Refsum H, Ebbing M, Nordrehaug JE, Nygård O. Effect of homocysteine-lowering B vitamin treatment on angiographic progression of coronary artery disease: a Western Norway B Vitamin Intervention Trial (WENBIT) substudy. Am J Cardiol. 2010 Jun 1;105(11):1577-84. doi: 10.1016/j.amjcard.2010.01.019
  48. Albert CM, Cook NR, Gaziano JM, Zaharris E, MacFadyen J, Danielson E, Buring JE, Manson JE. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA. 2008 May 7;299(17):2027-36. doi: 10.1001/jama.299.17.2027
  49. Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ, Sides EG, Wang CH, Stampfer M. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA. 2004 Feb 4;291(5):565-75. doi: 10.1001/jama.291.5.565
  50. Azzini E, Ruggeri S, Polito A. Homocysteine: Its Possible Emerging Role in At-Risk Population Groups. Int J Mol Sci. 2020 Feb 20;21(4):1421. doi: 10.3390/ijms2104142
  51. Esse R., Barroso M., Almeida I., Castro R. The contribution of homocysteine metabolism disruption to endothelial dysfunction: State-of-the-art. Int. J. Mol. Sci. 2019;20:867. doi: 10.3390/ijms20040867
  52. Steenge G.R., Verhoef P., Katan M.B. Betaine supplementation lowers plasma HCY in healthy men and women. J. Nutr. 2003;133:1291–1295. doi: 10.1093/jn/133.5.1291
  53. Olthof M.R., van Vliet T., Boelsma E., Verhoef P. Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J. Nutr. 2003;133:4135–4138. doi: 10.1093/jn/133.12.4135
  54. McRae M.P. Betaine supplementation decreases plasma homocysteine in healthy adult participants: A meta-analysis. J. Chiropr. Med. 2013;12:20–25. doi: 10.1016/j.jcm.2012.11.001
  55. Zaric L.B., Obradovic M., Bajic V., Haidara M.A., Jovanovic M., Isenovic E.R. Homocysteine and Hyperhomocysteinaemia. Curr. Med. Chem. 2019;26:2948–2961. doi: 10.2174/0929867325666180313105949
  56. Verhoef P., van Vliet T., Olthof M.R., Katan M.B. A high-protein diet increases postprandial but not fasting plasma total homocysteine concentrations: A dietary controlled, crossover trial in healthy volunteers. Am. J. Clin. Nutr. 2005;82:553–558. doi: 10.1093/ajcn/82.3.553
  57. Larsson SC, Orsini N, Wolk A. Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies. JAMA. 2010 Mar 17;303(11):1077-83. doi: 10.1001/jama.2010.263
  58. Wu W, Kang S, Zhang D. Association of vitamin B6, vitamin B12 and methionine with risk of breast cancer: a dose-response meta-analysis. Br J Cancer. 2013 Oct 1;109(7):1926-44. doi: 10.1038/bjc.2013.438
  59. Xiao Q, Freedman ND, Ren J, Hollenbeck AR, Abnet CC, Park Y. Intakes of folate, methionine, vitamin B6, and vitamin B12 with risk of esophageal and gastric cancer in a large cohort study. Br J Cancer. 2014 Mar 4;110(5):1328-33. doi: 10.1038/bjc.2014.17
  60. Zhang XH, Ma J, Smith-Warner SA, Lee JE, Giovannucci E. Vitamin B6 and colorectal cancer: current evidence and future directions. World J Gastroenterol. 2013 Feb 21;19(7):1005-10. doi: 10.3748/wjg.v19.i7.1005
  61. Song Y, Manson JE, Lee IM, Cook NR, Paul L, Selhub J, Giovannucci E, Zhang SM. Effect of combined folic acid, vitamin B(6), and vitamin B(12) on colorectal adenoma. J Natl Cancer Inst. 2012 Oct 17;104(20):1562-75. doi: 10.1093/jnci/djs370
  62. Ebbing M, Bønaa KH, Nygård O, Arnesen E, Ueland PM, Nordrehaug JE, Rasmussen K, Njølstad I, Refsum H, Nilsen DW, Tverdal A, Meyer K, Vollset SE. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA. 2009 Nov 18;302(19):2119-26. doi: 10.1001/jama.2009.1622
  63. Selhub J, Bagley LC, Miller J, Rosenberg IH. B vitamins, homocysteine, and neurocognitive function in the elderly. Am J Clin Nutr. 2000 Feb;71(2):614S-620S. doi: 10.1093/ajcn/71.2.614s
  64. Balk EM, Raman G, Tatsioni A, Chung M, Lau J, Rosenberg IH. Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials. Arch Intern Med. 2007 Jan 8;167(1):21-30. doi: 10.1001/archinte.167.1.21
  65. Riggs KM, Spiro A 3rd, Tucker K, Rush D. Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am J Clin Nutr. 1996 Mar;63(3):306-14. doi: 10.1093/ajcn/63.3.306
  66. Pawelec G, Goldeck D, Derhovanessian E. Inflammation, ageing and chronic disease. Curr Opin Immunol. 2014 Aug;29:23-8. doi: 10.1016/j.coi.2014.03.007
  67. Ford AH, Almeida OP. Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials. J Alzheimers Dis. 2012;29(1):133-49. doi: 10.3233/JAD-2012-111739
  68. Hankey GJ, Ford AH, Yi Q, Eikelboom JW, Lees KR, Chen C, Xavier D, Navarro JC, Ranawaka UK, Uddin W, Ricci S, Gommans J, Schmidt R, Almeida OP, van Bockxmeer FM; VITATOPS Trial Study Group. Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis. Stroke. 2013 Aug;44(8):2232-9. doi: 10.1161/STROKEAHA.113.001886
  69. Douaud G, Refsum H, de Jager CA, Jacoby R, Nichols TE, Smith SM, Smith AD. Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9523-8. doi: 10.1073/pnas.1301816110
  70. Hackett ML, Yapa C, Parag V, Anderson CS. Frequency of depression after stroke: a systematic review of observational studies. Stroke. 2005 Jun;36(6):1330-40. doi: 10.1161/01.STR.0000165928.19135.35
  71. Lenze EJ, Munin MC, Skidmore ER, Dew MA, Rogers JC, Whyte EM, Quear T, Begley A, Reynolds CF 3rd. Onset of depression in elderly persons after hip fracture: implications for prevention and early intervention of late-life depression. J Am Geriatr Soc. 2007 Jan;55(1):81-6. doi: 10.1111/j.1532-5415.2006.01017.x
  72. Merete C, Falcon LM, Tucker KL. Vitamin B6 is associated with depressive symptomatology in Massachusetts elders. J Am Coll Nutr. 2008 Jun;27(3):421-7. doi: 10.1080/07315724.2008.10719720
  73. Pan WH, Chang YP, Yeh WT, Guei YS, Lin BF, Wei IL, Yang FL, Liaw YP, Chen KJ, Chen WJ. Co-occurrence of anemia, marginal vitamin B6, and folate status and depressive symptoms in older adults. J Geriatr Psychiatry Neurol. 2012 Sep;25(3):170-8. doi: 10.1177/0891988712458365
  74. Skarupski KA, Tangney C, Li H, Ouyang B, Evans DA, Morris MC. Longitudinal association of vitamin B-6, folate, and vitamin B-12 with depressive symptoms among older adults over time. Am J Clin Nutr. 2010 Aug;92(2):330-5. doi: 10.3945/ajcn.2010.29413
  75. Almeida OP, Marsh K, Alfonso H, Flicker L, Davis TM, Hankey GJ. B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial. Ann Neurol. 2010 Oct;68(4):503-10. doi: 10.1002/ana.22189
  76. Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Intake of vitamins B6 and C and the risk of kidney stones in women. J Am Soc Nephrol. 1999 Apr;10(4):840-5. doi: 10.1681/ASN.V104840
  77. Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol. 2004 Dec;15(12):3225-32. doi: 10.1097/01.ASN.0000146012.44570.20
  78. Chetyrkin SV, Kim D, Belmont JM, Scheinman JI, Hudson BG, Voziyan PA. Pyridoxamine lowers kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria. Kidney Int. 2005 Jan;67(1):53-60. doi: 10.1111/j.1523-1755.2005.00054.x
  79. Scheinman JI, Voziyan PA, Belmont JM, Chetyrkin SV, Kim D, Hudson BG. Pyridoxamine lowers oxalate excretion and kidney crystals in experimental hyperoxaluria: a potential therapy for primary hyperoxaluria. Urol Res. 2005 Nov;33(5):368-71. doi: 10.1007/s00240-005-0493-3 Erratum in: Urol Res. 2006 Feb;34(1):67.
  80. Wyatt KM, Dimmock PW, Jones PW, Shaughn O’Brien PM. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review. BMJ. 1999 May 22;318(7195):1375-81. doi: 10.1136/bmj.318.7195.1375
  81. Kashanian M, Mazinani R, Jalalmanesh S, Babayanzad Ahari S. Pyridoxine (vitamin B6) therapy for premenstrual syndrome. Int J Gynaecol Obstet. 2007 Jan;96(1):43-4. doi: 10.1016/j.ijgo.2006.09.014 Erratum in: Int J Gynaecol Obstet. 2020 Jul;150(1):135.
  82. Bendich A. The potential for dietary supplements to reduce premenstrual syndrome (PMS) symptoms. J Am Coll Nutr. 2000 Feb;19(1):3-12. doi: 10.1080/07315724.2000.10718907
  83. Whelan AM, Jurgens TM, Naylor H. Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review. Can J Clin Pharmacol. 2009 Fall;16(3):e407-29.
  84. Niebyl JR. Clinical practice. Nausea and vomiting in pregnancy. N Engl J Med. 2010 Oct 14;363(16):1544-50. doi: 10.1056/NEJMcp1003896. Erratum in: N Engl J Med. 2010 Nov 18;363(21):2078.
  85. Matthews A, Dowswell T, Haas DM, Doyle M, O’Mathúna DP. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev. 2010 Sep 8;(9):CD007575. doi: 10.1002/14651858.CD007575.pub2. Update in: Cochrane Database Syst Rev. 2014;3:CD007575
  86. Maltepe C, Koren G. The management of nausea and vomiting of pregnancy and hyperemesis gravidarum–a 2013 update. J Popul Ther Clin Pharmacol. 2013;20(2):e184-92.
  87. Magee LA, Mazzotta P, Koren G. Evidence-based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP). Am J Obstet Gynecol. 2002 May;186(5 Suppl Understanding):S256-61. doi: 10.1067/mob.2002.122596
  88. Shrim A, Boskovic R, Maltepe C, Navios Y, Garcia-Bournissen F, Koren G. Pregnancy outcome following use of large doses of vitamin B6 in the first trimester. J Obstet Gynaecol. 2006 Nov;26(8):749-51. doi: 10.1080/01443610600955826
  89. Sahakian V, Rouse D, Sipes S, Rose N, Niebyl J. Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind placebo-controlled study. Obstet Gynecol. 1991 Jul;78(1):33-6.
  90. Vutyavanich T, Wongtra-ngan S, Ruangsri R. Pyridoxine for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol. 1995 Sep;173(3 Pt 1):881-4. doi: 10.1016/0002-9378(95)90359-3
  91. Koren G, Clark S, Hankins GD, Caritis SN, Miodovnik M, Umans JG, Mattison DR. Effectiveness of delayed-release doxylamine (an antihistamine) and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial. Am J Obstet Gynecol. 2010 Dec;203(6):571.e1-7. doi: 10.1016/j.ajog.2010.07.030
  92. American College of Obstetrics and Gynecology. ACOG (American College of Obstetrics and Gynecology) Practice Bulletin: nausea and vomiting of pregnancy. Obstet Gynecol. 2004 Apr;103(4):803-14.
  93. Pearl PL, Gospe SM Jr. Pyridoxine or pyridoxal-5′-phosphate for neonatal epilepsy: the distinction just got murkier. Neurology. 2014 Apr 22;82(16):1392-4. doi: 10.1212/WNL.0000000000000351
  94. Stockler S, Plecko B, Gospe SM Jr, Coulter-Mackie M, Connolly M, van Karnebeek C, Mercimek-Mahmutoglu S, Hartmann H, Scharer G, Struijs E, Tein I, Jakobs C, Clayton P, Van Hove JL. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Mol Genet Metab. 2011 Sep-Oct;104(1-2):48-60. doi: 10.1016/j.ymgme.2011.05.014
  95. Sacharow SJ, Picker JD, Levy HL. Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency. 2004 Jan 15 [Updated 2017 May 18]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1524
  96. Ellis J, Folkers K, Watanabe T, Kaji M, Saji S, Caldwell JW, Temple CA, Wood FS. Clinical results of a cross-over treatment with pyridoxine and placebo of the carpal tunnel syndrome. Am J Clin Nutr. 1979 Oct;32(10):2040-6. doi: 10.1093/ajcn/32.10.2040
  97. Ellis JM, Kishi T, Azuma J, Folkers K. Vitamin B6 deficiency in patients with a clinical syndrome including the carpal tunnel defect. Biochemical and clinical response to therapy with pyridoxine. Res Commun Chem Pathol Pharmacol. 1976 Apr;13(4):743-57.
  98. Keniston RC, Nathan PA, Leklem JE, Lockwood RS. Vitamin B6, vitamin C, and carpal tunnel syndrome. A cross-sectional study of 441 adults. J Occup Environ Med. 1997 Oct;39(10):949-59. doi: 10.1097/00043764-199710000-00007
  99. Aufiero E, Stitik TP, Foye PM, Chen B. Pyridoxine hydrochloride treatment of carpal tunnel syndrome: a review. Nutr Rev. 2004 Mar;62(3):96-104. doi: 10.1111/j.1753-4887.2004.tb00030.x
  100. Ryan-Harshman M, Aldoori W. Carpal tunnel syndrome and vitamin B6. Can Fam Physician. 2007 Jul;53(7):1161-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1949298
  101. Natural Medicines Comprehensive Database. Vitamin B6. 2011. http://naturaldatabase.therapeuticresearch.com/home.aspx?cs=&s=ND
  102. Simpson JL, Bailey LB, Pietrzik K, Shane B, Holzgreve W. Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess. Part I–Folate, Vitamin B12, Vitamin B6. J Matern Fetal Neonatal Med. 2010 Dec;23(12):1323-43. doi: 10.3109/14767051003678234
  103. Morris MS, Picciano MF, Jacques PF, Selhub J. Plasma pyridoxal 5′-phosphate in the US population: the National Health and Nutrition Examination Survey, 2003-2004. Am J Clin Nutr. 2008 May;87(5):1446-54. doi: 10.1093/ajcn/87.5.1446
  104. Bailey RL, Gahche JJ, Lentino CV, Dwyer JT, Engel JS, Thomas PR, Betz JM, Sempos CT, Picciano MF. Dietary supplement use in the United States, 2003-2006. J Nutr. 2011 Feb;141(2):261-6. doi: 10.3945/jn.110.133025
  105. U.S. Department of Agriculture, Agricultural Research Service. 2011. USDA National Nutrient Database for Standard Reference, Release 24. Nutrient Data Laboratory Home Page. https://www.ars.usda.gov/northeast-area/beltsville-md/beltsville-human-nutrition-research-center/nutrient-data-laboratory/
  106. Subar AF, Krebs-Smith SM, Cook A, Kahle LL. Dietary sources of nutrients among US adults, 1989 to 1991. J Am Diet Assoc. 1998 May;98(5):537-47. doi: 10.1016/S0002-8223(98)00122-9
  107. Food Labeling: Revision of the Nutrition and Supplement Facts Labels. https://www.federalregister.gov/documents/2016/05/27/2016-11867/food-labeling-revision-of-the-nutrition-and-supplement-facts-labels
  108. Brown MJ, Ameer MA, Beier K. Vitamin B6 Deficiency. [Updated 2022 Jul 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470579
  109. Altun H, Şahin N, Belge Kurutaş E, Güngör O. Homocysteine, Pyridoxine, Folate and Vitamin B12 Levels in Children with Attention Deficit Hyperactivity Disorder. Psychiatr Danub. 2018 Sep;30(3):310-316. doi: 10.24869/psyd.2018.310
  110. Bailey R.L., West K.P., Jr., Black R.E. The epidemiology of global micronutrient deficiencies. Ann. Nutr. Metab. 2015;66(Suppl. 2):22–33. doi: 10.1159/000371618
  111. Sawhney A, Singhal S, Patel R. Isolated Pyridoxine Deficiency Presenting as Peripheral Neuropathy Post-chemotherapy. Cureus. 2022 Jul 10;14(7):e26725. doi: 10.7759/cureus.26725
  112. Wang HS, Kuo MF. Vitamin B6 related epilepsy during childhood. Chang Gung Med J. 2007 Sep-Oct;30(5):396-401. http://cgmj.cgu.edu.tw/3005/300502.pdf
  113. Mayengbam S, Chleilat F, Reimer RA. Dietary Vitamin B6 Deficiency Impairs Gut Microbiota and Host and Microbial Metabolites in Rats. Biomedicines. 2020 Nov 2;8(11):469. doi: 10.3390/biomedicines8110469
  114. Hellmann H., Mooney S. Vitamin B6: A molecule for human health? Molecules. 2010;15:442–459. doi: 10.3390/molecules15010442
  115. Matxain J.M., Padro D., Ristila M., Strid A., Eriksson L.A. Evidence of high *OH radical quenching efficiency by vitamin B6. J. Phys. chem. B. 2009;113:9629–9632. doi: 10.1021/jp903023c
  116. Bird RP. The Emerging Role of Vitamin B6 in Inflammation and Carcinogenesis. Adv Food Nutr Res. 2018;83:151-194. doi: 10.1016/bs.afnr.2017.11.004
  117. Jung HY, Kim W, Hahn KR, Kwon HJ, Nam SM, Chung JY, Yoon YS, Kim DW, Yoo DY, Hwang IK. Effects of Pyridoxine Deficiency on Hippocampal Function and Its Possible Association with V-Type Proton ATPase Subunit B2 and Heat Shock Cognate Protein 70. Cells. 2020 Apr 25;9(5):1067. doi: 10.3390/cells9051067
  118. Walden M., Tian L., Ross R.L., Sykora U.M., Byrne D.P., Hesketh E.L., Masandi S.K., Cassel J., George R., Ault J.R., et al. Metabolic control of BRISC-SHMT2 assembly regulates immune signalling. Nature. 2019;570:194–199. doi: 10.1038/s41586-019-1232-1
  119. Qian B., Shen S., Zhang J., Jing P. Effects of vitamin B6 deficiency on the composition and functional potential of T cell populations. J. Immunol. Res. 2017;2017:2197975. doi: 10.1155/2017/2197975
  120. Mackey AD, Davis SR, Gregory JF. , III. In: Modern Nutrition in Health and Disease. Shils ME, Shike M, Ross AC, Cabellero B, Cousins RJ, editor. Philadelphia: Lippencott; 2006. Vitamin B6; pp. 452–461.
  121. Centers for Disease Control and Prevention . Second National Report on Biochemical Indicators of Diet and Nutrition in the U.S. Population. National Center for Environmental Health; Atlanta, GA, USA: Apr, 2012. https://www.cdc.gov/nutritionreport/pdf/Nutrition_Book_complete508_final.pdf
  122. Pyridoxine Deficiency. https://emedicine.medscape.com/article/124947-overview#a7
  123. Joyce T, Brown FC, Adalat S, Reid CJD, Sinha MD. Vitamin B6 blood concentrations in paediatric dialysis patients. Pediatr Nephrol. 2018 Nov;33(11):2161-2165. doi: 10.1007/s00467-018-4053-9
  124. Echaniz-Laguna A, Mourot-Cottet R, Noel E, Chanson JB. Regressive pyridoxine-induced sensory neuronopathy in a patient with homocystinuria. BMJ Case Rep. 2018 Jun 28;2018:bcr2018225059. doi: 10.1136/bcr-2018-225059
  125. Strobbe S, Van Der Straeten D. Toward Eradication of B-Vitamin Deficiencies: Considerations for Crop Biofortification. Front Plant Sci. 2018 Apr 6;9:443. doi: 10.3389/fpls.2018.00443
  126. Banihani SA. A Systematic Review Evaluating the Effect of Vitamin B6 on Semen Quality. Urol J. 2017 Dec 30;15(1):1-5. doi: 10.22037/uj.v0i0.3808
  127. Jankowska M, Marszałł M, Dębska-Ślizień A, Carrero JJ, Lindholm B, Czarnowski W, Rutkowski B, Trzonkowski P. Vitamin B6 and the immunity in kidney transplant recipients. J Ren Nutr. 2013 Jan;23(1):57-64. doi: 10.1053/j.jrn.2012.01.023
  128. Henning BF, Zidek W, Riezler R, Graefe U, Tepel M. Homocyst(e)ine metabolism in hemodialysis patients treated with vitamins B6, B12 and folate. Res Exp Med (Berl). 2001 Mar;200(3):155-68.
  129. Woolf K, Manore MM. Elevated plasma homocysteine and low vitamin B-6 status in nonsupplementing older women with rheumatoid arthritis. J Am Diet Assoc. 2008 Mar;108(3):443-53; discussion 454. doi: 10.1016/j.jada.2007.12.001
  130. Chiang EP, Smith DE, Selhub J, Dallal G, Wang YC, Roubenoff R. Inflammation causes tissue-specific depletion of vitamin B6. Arthritis Res Ther. 2005;7(6):R1254-62. doi: 10.1186/ar1821
  131. Kelly PJ, Kistler JP, Shih VE, Mandell R, Atassi N, Barron M, Lee H, Silveira S, Furie KL. Inflammation, homocysteine, and vitamin B6 status after ischemic stroke. Stroke. 2004 Jan;35(1):12-5. doi: 10.1161/01.STR.0000106481.59944.2F
  132. Balasa VV, Kalinyak KA, Bean JA, Stroop D, Gruppo RA. Hyperhomocysteinemia is associated with low plasma pyridoxine levels in children with sickle cell disease. J Pediatr Hematol Oncol. 2002 Jun-Jul;24(5):374-9. doi: 10.1097/00043426-200206000-00010
  133. Kaczorowska M, Kmiec T, Jakobs C, Kacinski M, Kroczka S, Salomons GS, Struys EA, Jozwiak S. Pyridoxine-dependent seizures caused by alpha amino adipic semialdehyde dehydrogenase deficiency: the first polish case with confirmed biochemical and molecular pathology. J Child Neurol. 2008 Dec;23(12):1455-9. doi: 10.1177/0883073808318543
  134. Striano P, Battaglia S, Giordano L, Capovilla G, Beccaria F, Struys EA, Salomons GS, Jakobs C. Two novel ALDH7A1 (antiquitin) splicing mutations associated with pyridoxine-dependent seizures. Epilepsia. 2009 Apr;50(4):933-6. doi: 10.1111/j.1528-1167.2008.01741.x
  135. Khayat M, Korman SH, Frankel P, Weintraub Z, Hershckowitz S, Sheffer VF, Elisha MB, Wevers RA, Falik-Zaccai TC. PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism. Mol Genet Metab. 2008 Aug;94(4):431-434. doi: 10.1016/j.ymgme.2008.04.008
  136. Merrill AH Jr, Henderson JM. Diseases associated with defects in vitamin B6 metabolism or utilization. Annu Rev Nutr. 1987;7:137-56. doi: 10.1146/annurev.nu.07.070187.001033
  137. Chiang EP, Selhub J, Bagley PJ, Dallal G, Roubenoff R. Pyridoxine supplementation corrects vitamin B6 deficiency but does not improve inflammation in patients with rheumatoid arthritis. Arthritis Res Ther. 2005;7(6):R1404-11. doi: 10.1186/ar1839
  138. Vech RL, Lumeng L, Li TK. Vitamin B6 metabolism in chronic alcohol abuse The effect of ethanol oxidation on hepatic pyridoxal 5′-phosphate metabolism. J Clin Invest. 1975 May;55(5):1026-32. doi: 10.1172/JCI108003
  139. Snider DE Jr. Pyridoxine supplementation during isoniazid therapy. Tubercle. 1980 Dec;61(4):191-6. doi: 10.1016/0041-3879(80)90038-0
  140. Raskin NH, Fishman RA. Pyridoxine-deficiency neuropathy due to hydralazine. N Engl J Med. 1965 Nov 25;273(22):1182-5. doi: 10.1056/NEJM196511252732203
  141. Nair S, Maguire W, Baron H, Imbruce R. The effect of cycloserine on pyridoxine-dependent metabolism in tuberculosis. J Clin Pharmacol. 1976 Aug-Sep;16(8-9):439-43. doi: 10.1002/j.1552-4604.1976.tb02419.x
  142. Apeland T, Frøyland ES, Kristensen O, Strandjord RE, Mansoor MA. Drug-induced pertubation of the aminothiol redox-status in patients with epilepsy: improvement by B-vitamins. Epilepsy Res. 2008 Nov;82(1):1-6. doi: 10.1016/j.eplepsyres.2008.06.003
  143. Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. Eur J Emerg Med. 2005 Apr;12(2):78-85. doi: 10.1097/00063110-200504000-00007
  144. Reynolds R.D. Bioavailability of vitamin B-6 from plant foods. Am. J. Clin. Nutr. 1988;48:863–867. doi: 10.1093/ajcn/48.3.863
  145. Roth-Maier D.A., Kettler S.I., Kirchgessner M. Availability of vitamin B6 from different food sources. Int. J. Food Sci. Nutr. 2002;53:171–179. doi: 10.1080/09637480220132184
  146. Schorgg P., Bärnighausen T., Rohrmann S., Cassidy A., Karavasiloglou N., Kühn T. Vitamin B6 Status among Vegetarians: Findings from a Population-Based Survey. Nutrients. 2021;13:1627. doi: 10.3390/nu13051627
  147. Pyridoxine Deficiency Treatment & Management. https://emedicine.medscape.com/article/124947-treatment#d5
  148. Pyridoxine Deficiency. https://emedicine.medscape.com/article/124947-overview
  149. Jung H.Y., Kim W., Hahn K.R., Kwon H.J., Nam S.M., Chung J.Y., Yoon Y.S., Kim D.W., Yoo D.Y., Hwang I.K. Effects of pyridoxine deficiency on hippocampal function and its possible association with V-type proton ATPase subunit B2 and heat shock cognate protein 70. Cells. 2020;9:1067. doi: 10.3390/cells9051067
  150. Spinneker A, Sola R, Lemmen V, Castillo MJ, Pietrzik K, González-Gross M. Vitamin B6 status, deficiency and its consequences–an overview. Nutr Hosp. 2007 Jan-Feb;22(1):7-24.
  151. Merck Sharp & Dohme Corp., Merck Manual. Vitamin B6. https://www.merckmanuals.com/professional/nutritional-disorders/vitamin-deficiency,-dependency,-and-toxicity/vitamin-b-6
  152. HUNT AD Jr, STOKES J Jr, McCRORY WW, STROUD HH. Pyridoxine dependency: report of a case of intractable convulsions in an infant controlled by pyridoxine. Pediatrics. 1954 Feb;13(2):140-5.
  153. Agadi S, Quach MM, Haneef Z. Vitamin-responsive epileptic encephalopathies in children. Epilepsy Res Treat. 2013;2013:510529. doi: 10.1155/2013/510529
  154. Rollón N, Fernández-Jiménez MC, Moreno-Carralero MI, Murga-Fernández MJ, Morán-Jiménez MJ. Microcytic anemia in a pregnant woman: beyond iron deficiency. Int J Hematol. 2015 May;101(5):514-9. doi: 10.1007/s12185-014-1723-7
  155. Mayengbam S, House JD, Aliani M. Investigation of vitamin B₆ inadequacy, induced by exposure to the anti-B₆ factor 1-amino D-proline, on plasma lipophilic metabolites of rats: a metabolomics approach. Eur J Nutr. 2016 Apr;55(3):1213-23. doi: 10.1007/s00394-015-0934-x
  156. Ubbink JB, Serfontein WJ, de Villiers LS. Stability of pyridoxal-5-phosphate semicarbazone: applications in plasma vitamin B6 analysis and population surveys of vitamin B6 nutritional status. J Chromatogr. 1985 Aug 9;342(2):277-84. doi: 10.1016/s0378-4347(00)84518-1
  157. Pyridoxine Deficiency Treatment & Management. https://emedicine.medscape.com/article/124947-treatment
  158. Badrinath M, John S. Isoniazid Toxicity. [Updated 2022 Jun 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK531488
  159. Pyridoxine Deficiency. https://emedicine.medscape.com/article/124947-overview#a2
  160. Meyer HE, Willett WC, Fung TT, Holvik K, Feskanich D. Association of High Intakes of Vitamins B6 and B12 From Food and Supplements With Risk of Hip Fracture Among Postmenopausal Women in the Nurses’ Health Study. JAMA Netw Open. 2019 May 3;2(5):e193591. doi: 10.1001/jamanetworkopen.2019.3591
  161. Bender DA. Non-nutritional uses of vitamin B6. Br J Nutr. 1999 Jan;81(1):7-20. https://core.ac.uk/reader/1804412
  162. Morris MS, Picciano MF, Jacques PF, Selhub J. Plasma pyridoxal 5′-phosphate in the US population: the National Health and Nutrition Examination Survey, 2003-2004. Am J Clin Nutr. 2008 May;87(5):1446-54. doi: 10.1093/ajcn/87.5.1446.
  163. Bendich A, Cohen M. Vitamin B6 safety issues. Ann N Y Acad Sci. 1990;585:321-30. doi: 10.1111/j.1749-6632.1990.tb28064.x
  164. Gdynia HJ, Müller T, Sperfeld AD, Kühnlein P, Otto M, Kassubek J, Ludolph AC. Severe sensorimotor neuropathy after intake of highest dosages of vitamin B6. Neuromuscul Disord. 2008 Feb;18(2):156-8. doi: 10.1016/j.nmd.2007.09.009
  165. Perry TA, Weerasuriya A, Mouton PR, Holloway HW, Greig NH. Pyridoxine-induced toxicity in rats: a stereological quantification of the sensory neuropathy. Exp Neurol. 2004 Nov;190(1):133-44. doi: 10.1016/j.expneurol.2004.07.013
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