Key Takeaways (expand)
- Vitamin B6, sometimes called pyridoxine, is a group of of six water-soluble compounds with a similar chemical structure, all containing a pyridine ring as their core.
- All forms of vitamin B6 can be enzymatically converted into the active form of B6, pyridoxal 5’-phospate (PLP); in this form, they express their vitamin activity.
- Vitamin B6 is needed for the function of over 100 PLP-dependent enzymes, particularly those involved in protein metabolism, hemoglobin synthesis, fatty acid metabolism, gluconeogenesis, selenium metabolism, platelet aggregation inhibition, and the release of glucose from glycogen.
- Vitamin B6 is also needed for producing the key neurotransmitters dopamine and serotonin, as well as other neurotransmitters such as glycine, GABA, glutamate, histamine, epinephrine, and norepinephrine.
- Like other B vitamins, vitamin B6 is needed for energy metabolism, with a specific role in producing NAD—a coenzyme that gets reduced to NADH to shuttle electrons in the final step of the Krebs cycle, ultimately producing ATP, the energy currency of cells.
- Higher vitamin B6 intake is linked to lower risk of heart disease, while low blood levels of vitamin B6 (in the form of PLP) is associated with increased cardiovascular disease risk; this may be due to the role of vitamin B6 in metabolizing homocysteine, and/or its impact on inflammation.
- Vitamin B6 seems to modify cancer risk as well, with prospective studies showing that higher vitamin B6 or serum PLP levels are associated with lower risk of esophageal, stomach, and colorectal cancer.
- Risk of late-life depression appears to increase for people with low vitamin B6 status, possibly due to the role of this vitamin in producing neurotransmitters; likewise, supplementing with vitamin B6 after events known to increase depression risk (such as stroke) may help reduce the occurrence of a major depressive episode.
- Some preliminary evidence suggests vitamin B6 could impact hormone function—influencing the activity of steroid receptors for hormones like testosterone, progesterone, and estrogen.
- High doses of vitamin B6 may help treat morning sickness during pregnancy, as well as reduce some symptoms of PMS.
- Severe vitamin B6 deficiency is uncommon, but is most likely to occur among alcoholics, people with impaired kidney function, people with autoimmune disorders, and those with malabsorption syndromes.
- Vitamin B6 deficiency can lead to a range of physical and neurological symptoms, including abnormal electroencephalogram (EEG) patterns, ulcers, rashes, weakened immune system, inflamed tongue, drowsiness, irritability, confusion, depression, and peripheral neuropathy; in infants, vitamin B6 deficiency can produce seizures.
- The best sources of vitamin B6 are fish, green leafy vegetables, root vegetables, many fruits, legumes, red meat, poultry, as seeds.
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Vitamin B6 actually refers to a group of six water-soluble compounds with a similar chemical structure, all containing a pyridine ring as their core: pyridoxal (an aldehyde), pyridoxine (an alcohol), pyridoxamine (which contains an amino group), as well their phosphorylated derivatives (pyridoxal 5’-phosphate, pyridoxine 5’-phosphate, and pyridoxamine 5′-phosphate, respectively). All forms of vitamin B6 owe their vitamin activity to their ability to be enzymatically converted into the active form of B6, pyridoxal 5’-phospate. Vitamin B6 is sometimes used interchangeably with the name pyridoxine, the version of B6 commonly used in foods and supplements (though this clearly isn’t the whole vitamin B6 picture!).
Vitamin B6 was first identified in 1934 during experiments with rats, when the Hungarian physician Paul György discovered a factor that could cure the animals’ dermatitis acrodynia—a skin disease they developed in response to vitamin-free diets. He named the vitamin “B6” due to the standard practice of numbering vitamins in chronological order (the previously discovered one being B5, or pantothenic acid). In 1938, the vitamin was officially isolated and crystalized, and was soon shown to be a pyridine derivative—at which point, György proposed the name pyridoxine, a combination of “pyridine” and “oxygen.”
Like other B vitamins, it plays an important role in energy metabolism—breaking down the carbohydrates, fat, and protein we eat for use as fuel (hence why B-complex vitamins are often nicknamed the “energy vitamins!”), as well as neurotransmitter production, cellular function, and a wide variety of organ functions.
Good sources of vitamin B6 include fish, leafy greens, root vegetables, fruit such as bananas, legumes such as chickpeas, red meat, poultry, and seeds (especially sunflower and pumpkin). Some processed foods, like breakfast cereals, are also fortified with vitamin B6.
The Biological Roles of Vitamin B6
Vitamin B6 and its derivative, pyridoxal 5’-phosphate (PLP), are needed for over 100 different enzymes to function—most of which are involved in protein metabolism (including transaminations, racemizations, decarboxylations, and a variety of modifications to amino acid side chains). PLP is also required for a huge number of other enzymatic processes, including hemoglobin synthesis (needed for carrying oxygen through the blood), fatty acid metabolism, glucose production from amino acids (gluconeogenesis), the breakdown of methionine, the conversion of dietary selenium into its biologically active form, the biosynthesis of sphingolipids (fatty acid derivatives that participate in tissue development, toxin metabolism, and cell recognition and adhesion), expression of genes involved in glucocorticoid transcription, platelet aggregation inhibition, and the release of glucose from stored glycogen. In fact, PLP is involved in over 4% of all enzymatic reactions in the body—and given how many of these reactions are occurring every minute, that ends up being a huge number!
Overall, PLP-dependent enzymes fall into one of five structural classes known as fold types: Fold Type I is the aspartate aminotransferase family; Fold Type II is the tryptophan synthase family; Fold Type III is the alanine racemase family; Fold Type IV is the D-amino acid aminotransferase family; and Fold Type V is the glycogen phosphorylase family.
Vitamin B6 is also needed for the production of the key neurotransmitters dopamine and serotonin; this is mainly through a PLP-dependent enzyme called aromatic L-amino acid decarboxylase, which helps synthesize these neurotransmitters from tryptophan and L-3,4-dihydroxyphenylalanine (L-Dopa), respectively. Additional PLP-dependent enzymes help synthesize other neurotransmitters, too, including glycine, glutamate, GABA, histamine, epinephrine, and norepinephrine. Vitamin B6 also helps maintain the chemical balance among body fluids.
Like other B vitamins, it also plays an important role in energy metabolism—particularly the second stage of cellular respiration, called the Krebs cycle or citric acid cycle. The Krebs cycle is an incredibly important series of chemical reactions that all aerobic organisms use to generate energy, through an eight-step process taking place in a cell’s mitochondria. During this cycle, acetate (in the form of acetyl CoA) derived from carbohydrates, fat, or protein undergoes a series of redox, dehydration, hydration, and decarboxylation reactions to produce adenosine triphosphate (ATP), the energy currency for all cells—as well as the waste product carbon dioxide, and reduced forms of NADH and FADH2 (which can then be converted into yet more ATP in the last step of the Krebs cycle: oxidative phosphorylation in the electron transport chain). This is complex biochemistry, but the important part here is that there are a whole lot of chemical reactions required to produce energy for our cells, and B vitamins are essential for that process!
Vitamin B6, specifically, plays an important role in this cycle through its interactions with other nutrients. More specifically, vitamin B6 in the form of PLP is needed to convert tryptophan to niacin and producing NAD—a coenzyme that gets reduced to NADH and serves as a shuttle for electrons in the final step of the Krebs cycle, ultimately producing the all-important ATP. Reduced PLP availability has been shown to limit NAD production, whereas adequate PLP availability helps support it, keeping the Krebs cycle running!
Vitamin B6 in Health and Disease
Vitamin B6 plays a role in the prevention and treatment of a number of diseases. Studies link higher vitamin B6 intake to a lower risk of heart disease and certain cancers, including stomach cancer, colorectal cancer, and esophageal cancer. Vitamin B6 also appears protective against late-life depression, especially after medical events like stroke. There’s some preliminary evidence that vitamin B6 can impact hormone function, namely by influencing the activity of steroid receptors for estrogen, progesterone, and testosterone. As a high-dose supplement, it’s even been used to treat morning sickness and PMS symptoms (including mood changes)!
Vitamin B6 and Cardiovascular Disease
There’s evidence for a link between vitamin B6 intake and cardiovascular disease risk.
Multiple large observational studies have found that participants with the highest intake of vitamin B6 had anywhere from a 34% to 48% lower risk of developing heart disease compared to people with the lowest intake of this nutrient. Likewise, low blood levels of vitamin B6 (in the form of PLP) tend to associate with elevated homocysteine levels and increased cardiovascular disease risk—in some studies, a near-doubling of heart disease risk among people with low blood PLP levels (under 30 nanomoles per) compared to people with higher PLP levels (at least 30 nanomoles per liter), and a 79% reduced risk of heart attack specifically among people with blood PLP levels of at least 70 nanomoles per liter.
This relationship could be due to the role of vitamin B6 in metabolizing homocysteine, an amino acid that’s been linked to cardiovascular disease development when present at high levels in the blood; two PLP-dependent enzymes are needed for converting homocysteine into the amino acid cysteine. But, while human experiments have shown that homocysteine levels rise more dramatically after a meal among people with marginal B6 deficiency compared to people with adequate B6 status, studies have failed to demonstrate that vitamin B6 intake or supplementation can lower fasting levels of homocysteine; another B vitamin, folate, is more effective for this.
Vitamin B6 and Inflammation
It’s also possible that this micronutrient influences heart disease risk via its impact on inflammation. Multiple observational studies have found that both vitamin B6 intake and blood levels of PLP are inversely associated with markers of inflammation, particularly C-reactive protein and fibrinogen—although this relationship may be more complicated than what first meets the eye, because along with vitamin B6 potentially influencing inflammation, systemic inflammation has been shown to impair vitamin B6 status, due to increasing the degradation of pyridoxal to 4-pyridoxic acid.
Vitamin B6 and Cancer
Cancer risk, too, may be modified by vitamin B6. A number of prospective studies have found that vitamin B6 and/or serum PLP levels are associated with a reduced risk of colorectal cancer, esophageal cancer, and stomach cancer; low levels of vitamin B6 are likewise associated with higher incidence. A link with breast cancer, however, has been inconsistent. A vitamin B6-cancer relationship could be due to the role of PLP in several pathways relevant to cancer, including the methionine cycle, thymidylate synthesis, and homocysteine catabolism.
Vitamin B6 and Late-Life Depression
Although studies investigating the role of vitamin B6 in cognitive decline and Alzheimer’s disease haven’t turned up any compelling evidence, vitamin B6 may help with another age-related neurological issue: late-life depression, a common disorder among the elderly—especially striking after acute illnesses like stroke or hip fracture.
Multiple observational studies have found a link between low vitamin B6 status and late-life depression, as well as total vitamin B6 intake and the incidence of depressive symptoms in the elderly. And, randomized controlled trials show that among patients who recently suffered from a stroke, supplementing with 25 mg of vitamin B6 daily (along with two other B vitamins, folic acid and vitamin B12) halved the risk of experiencing a major depressive episode over the course of the next seven years.
Given the role of PLP-dependent enzymes in producing important neurotransmitters, it’s possible that a beneficial effect of vitamin B6 on depression occurs through this route.
Vitamin B6 and Hormone Health
Limited—but intriguing—evidence suggest that vitamin B6 (in the form of PLP) can impact hormone function, influencing the activity of steroid receptors and decreasing their effects on gene expression. Specifically, PLP can interact with a repressor of nuclear receptors called RIP140/NRIP1, which has some important roles in reproductive biology. Although speculative so far, it’s possible that PLP can inhibit the activity of steroid receptors for hormones like progesterone, estrogen, and testosterone, making vitamin B6 potentially relevant in the development of hormone-related disease like breast cancer and prostate cancer. But, much more research is needed before we can say anything for certain!
High doses of vitamin B6 have a therapeutic benefit for several conditions. Since the 1940s, vitamin B6 has been used to treat morning sickness in pregnant individuals, and controlled trials have confirmed that it’s effective at reducing nausea during early pregnancy.
Studies also indicate that supplemental vitamin B6 (at doses of up to 100 mg per day) may help reduce some symptoms of PMS, including those related to mood.
Vitamin B6 and Kidney Stones
Similarly, vitamin B6 has a potential (but insufficiently researched) effect on kidney stone prevention. A large prospective study found that compared to women with the lowest intakes of vitamin B6, women consuming 40 mg or more each day had their risk of kidney stones cut by a third. Some controlled experiments, too, support a causative relationship here, with data showing that supplementing with pyridoxamine can reduce urinary oxalate levels and the subsequent formation of calcium oxalate kidney stones. But, the evidence so far is still too limited for vitamin B6 to be officially prescribed for kidney stones!
Health Effects of Vitamin B6 Deficiency
Severe vitamin B6 deficiency is uncommon, but tends to be more likely in alcoholics (due to both impaired metabolism and low dietary intakes), as well as people with impaired kidney function, autoimmune disorders (such as rheumatoid arthritis), malabsorption syndromes (like celiac disease, ulcerative colitis, and Crohn’s disease). When it does occur, B6 deficiency can lead to abnormal electroencephalogram (EEG) patterns, ulcers on the mouth and skin, rashes, weakened immune system, and inflammation of the tongue, as well as neurological symptoms like drowsiness, irritability, confusion, depression, and peripheral neuropathy (numbness or pain in the hands and feet, resulting from nerve damage). In infants, vitamin B6 deficiency can cause seizures (sadly, this was discovered in the 1950s when a manufacturing error in infant formulas led to babies becoming severely B6 deficient). Due to its role in hemoglobin synthesis, vitamin B6 deficiency can also lead to microcytic anemia—a form of anemia characterized by smaller-than-normal red blood cells.
Even with adequate intake, other factors can raise vitamin B6 needs and increase the risk of insufficiency. Both in vitro experiments and clinical trials have shown that systemic inflammation, involved in most chronic diseases, can impair the metabolism of vitamin B6. Some medications also interfere with B6 metabolism, including estrogen-containing oral contraceptives and methylxanthines (commonly used for treating respiratory conditions like asthma and COPD); anti-tuberculosis medications, Parkinson’s disease drugs like L-Dopa, and penicillamine (a metal chelator) are known to form complexes with vitamin B6 and make it less bioavailable, in turn raising the risk of deficiency. Long-term use of nonsteroidal anti-inflammatory drugs can also interfere with the metabolism of vitamin B6.
Although vegans and vegetarians don’t appear to be at significantly higher risk of vitamin B6 deficiency than meat eaters, it’s worth noting that plant foods tend to contain a unique form of B6 called pyridoxine glucoside, which is only about half as bioavailable as vitamin B6 from other foods and supplements.
Problems From Too Much Vitamin B6
Although it’s nearly impossible to eat enough vitamin B6 from food sources to experience toxicity (due to it being a water-soluble vitamin, meaning excess is excreted rather than stored), long-term, high-dose supplementation of pyridoxine (in excess of 1000 mg per day) can adversely affect the nervous system. In particular, sensory neuropathy can occur, which includes symptoms like pain, loss of coordination, burning sensations, numbness in the extremities, and difficulty walking. Skin lesions and gastrointestinal symptoms can also result from excessive vitamin B6. Luckily, no evidence of nerve damage exists from intakes below 200 mg of pyridoxine daily.
How Much Vitamin B6 Do We Need?
The recommended dietary allowance (RDA) for vitamin B6 is 1.3 mg for adults aged 19 to 50 (1.9 mg for day for pregnant women, and 2 mg per day during breastfeeding/lactation); for adults over 50, the RDA increases to 1.5 mg daily for women and 1.7 mg daily for men. However, the protective effects of vitamin B6 on conditions like heart disease, depression, kidney stones, and cancer are generally seen at higher intakes than these levels!
Best Food Sources of Vitamin B6
The following foods have high concentrations of vitamin B6, containing at least 50% of the recommended dietary allowance per serving, making them our best food sources of this valuable B-vitamin!
Good Food Sources of Vitamin B6
The following foods are also excellent or good sources of vitamin B6, containing at least 10% (and up to 50%) of the daily value per serving.
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