Herbal catalog

Vitamin B₆

Vitamin B₆ is a water-soluble vitamin that was first isolated in the 1930's. There are six forms of vitamin B₆: pyridoxal (PL), pyridoxine (PN), pyridoxamine (PM), and their phosphate derivatives: pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate (PNP), and pridoxamine 5'-phospate (PMP). PLP is the active coenzyme form, and has the most importance in human metabolism (1).

Function

Vitamin B₆ must be obtained from the diet because humans cannot synthesize it, and the coenzyme, PLP plays a vital role in the function of approximately 100 enzymes that catalyze essential chemical reactions in the human body (1, 2). For example, PLP functions as a coenzyme for glycogen phosphorylase, an enzyme that catalyzes the release of glucose stored in the muscle as glycogen. Much of the PLP in the human body is found in muscle bound to glycogen phosphorylase. PLP is also a coenzyme for reactions used to generate glucose from amino acids, a process known as gluconeogenesis.

Nervous system function

The synthesis of the neurotransmitter, serotonin, from the amino acid, tryptophan, in the brain is catalyzed by a PLP-dependent enzyme. Other neurotransmitters such as dopamine, norepinephrine and gamma-aminobutyric acid (GABA) are also synthesized using PLP-dependent enzymes (2).

Red blood cell formation and function

PLP functions as a coenzyme in the synthesis of heme, a component of hemoglobin. Hemoglobin is found in red blood cells and is critical to their ability to transport oxygen throughout the body. Both PL and 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 (2).

Niacin formation

The human requirement for another vitamin, niacin, can be met in part by the conversion of the dietary amino acid, tryptophan, to niacin, as well as through dietary intake. PLP is a coenzyme for a critical reaction in the synthesis of niacin from tryptophan. Thus, adequate vitamin B₆ decreases the requirement for niacin in the diet (2).

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 the cell and altering gene transcription. PLP binds to steroid receptors in such a manner as to inhibit the binding of steroid hormones, thus decreasing their effects. The binding of PLP to steroid receptors for estrogen, progesterone, testosterone, and other steroid hormones suggest that the vitamin B₆ status of an individual may have implications for diseases affected by steroid hormones, such as breast cancer and prostate cancer (2).

Nucleic acid synthesis

PLP serves as a coenzyme for a key enzyme involved in the mobilization of single-carbon functional groups (one-carbon metabolism). Such reactions are involved in the synthesis of nucleic acids. The effect of B₆ deficiency on immune system function may be partly related to the role of PLP in one-carbon metabolism (see Disease Prevention).

Deficiency

Severe deficiency of vitamin B₆ is uncommon. Alcoholics are thought to be most at risk of vitamin B₆ deficiency, due to a low intake and impaired metabolism of the vitamin. In the early 1950's seizures were observed in infants as a result of severe vitamin B₆ deficiency due to an error in the manufacture of infant formula. Abnormal electroencephalogram (EEG) patterns have been noted in some studies of vitamin B₆ deficiency. Other neurologic symptoms noted in severe vitamin B₆ deficiency include irritability, depression, and confusion; additional symptoms include inflammation of the tongue, sores or ulcers of the mouth, and ulcers of the skin at the corners of the mouth (1).

The Recommended Dietary Allowance (RDA)

Because vitamin B₆ is involved in so many aspects of metabolism, several factors are likely to affect an individual's requirement for vitamin B₆. Of those factors, protein intake has been studied the most. Increased dietary protein results in an increased requirement for vitamin B₆, probably because PLP is a coenzyme for many enzymes involved in amino acid metabolism (3). Unlike previous recommendations, the Food and Nutrition Board (FNB) of the Institute of Medicine did not express the most recent RDA for vitamin B6 in terms of protein intake, although the relationship was considered in setting the RDA (4). The current RDA was revised by the Food and Nutrition Board (FNB) in 1998 and is presented in the table below.

DISEASE PREVENTION

Homocysteine and cardiovascular disease

Even moderately elevated levels of homocysteine in the blood have been associated with increased risk for cardiovascular disease, including heart disease and stroke (5). When we digest protein, amino acids, including methionine, are released. Homocysteine is an intermediate in the metabolism of methionine. Healthy individuals utilize two different pathways to metabolize homocysteine. One pathway results in the conversion of homocysteine back to methionine, and is dependent on folic acid and vitamin B₁₂. The other pathway converts homocysteine to another amino acid, cysteine, and requires two vitamin B₆ (PLP)-dependent enzymes. Thus, the amount of homocysteine in the blood is regulated by at least three vitamins: folic acid, vitamin B₁₂, and vitamin B₆ (diagram). Several large observational studies have demonstrated an association between low vitamin B₆intake or status with increased blood homocysteine levels and increased risk of cardiovascular diseases. A large prospective study found the risk of heart disease in women who consumed, on average, 4.6 mg of vitamin B₆ daily to be only 67% of the risk in women who consumed an average of 1.1 mg daily (6). Another large prospective study found higher plasma levels of PLP to be associated with decreased risk of cardiovascular disease, independent of homocysteine levels (7). In contrast to folic acid supplementation, studies of vitamin B₆ supplementation alone have not resulted in significant decreases of basal (fasting) levels of homocysteine. However, vitamin B₆ supplementation has been found effective in lowering blood homocysteine levels after an oral dose of methionine (methionine load test) was given (8), suggesting it may play a role in the metabolism of homocysteine after meals.

Immune function

Low vitamin B₆ intake and nutritional status have been associated with impaired immune function, especially in the elderly. Decreased production of immune system cells known as lymphocytes, as well as decreased production of an important immune system protein called interleukin-2, have been measured in vitamin B₆ deficient individuals. Restoration of adequate vitamin B₆ status resulted in normalization of the lymphocyte proliferation and interleukin-2 production, suggesting that adequate vitamin B₆ intake is important for optimal immune system function in older individuals (9, 10). However, one study found that the amount of vitamin B₆ required to reverse these immune system impairments in the elderly was 2.9 mg/day for men and 1.9 mg/day for women, more than the current RDA (9).

Cognitive function

A few recent studies have demonstrated an association between declines in cognitive function or Alzheimer's disease in the elderly and inadequate nutritional status of folic acid, vitamin B₁₂, and vitamin B₆ and thus, elevated levels of homocysteine (11). One observational study found higher plasma vitamin B₆ levels to be associated with better performance on two measures of memory, but unrelated to performance on 18 other cognitive tests (12). It is presently unclear whether marginal B vitamin deficiencies, which are relatively common in the elderly, contribute to age-associated declines in cognitive function or whether both result from processes associated with aging and/or disease.

Kidney stones

A large prospective study examined the relationship between vitamin B₆ intake and the occurrence of symptomatic kidney stones in women. In a group of more than 85,000 women without a prior history of kidney stones, followed over 14 years, 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 (13). However, in a group of more than 45,000 men followed over 6 years, no association was found between vitamin B₆ intake and the occurrence of kidney stones (14). Limited data have shown that supplementation of vitamin B₆ at levels higher than the tolerable upper intake level (100 mg) decreased elevated urinary oxalate levels, an important determinant of calcium oxalate kidney stone formation, in some individuals. However, it is less clear that supplementation actually resulted in decreased formation of calcium oxalate kidney stones. Presently, the relationship between vitamin B₆ intake and the risk of developing kidney stones requires further study before any recommendation can be made.

Disease Treatment

Vitamin B₆ supplements at pharmacologic doses (i.e., doses much larger than those needed to prevent deficiency) have been used in an attempt to treat a wide variety of conditions, some of which are discussed below. In general, well designed, placebo-controlled studies have shown little evidence of benefit from large supplemental doses of vitamin B₆ (15).

Side effects of oral contraceptives

Because vitamin B₆ is required for the metabolism of the amino acid tryptophan, the tryptophan load test (an assay of tryptophan metabolites after an oral dose of tryptophan) was used as a functional assessment of vitamin B₆ status. Abnormal tryptophan load tests in women taking high-dose oral contraceptives in the 1960's and 1970's suggested that these women were vitamin B₆deficient. The abnormal results in the tryptophan load test led a number of clinicians to prescribe high doses (100-150 mg/day) of vitamin B₆ to women in order to relieve depression and other side effects sometimes experienced with oral contraceptives. However, most other indices of vitamin B₆ status were normal in women on high-dose oral contraceptives, and it is likely that the abnormality in tryptophan metabolism was not due to vitamin B₆ deficiency (15). A more recent study of women on the low-dose oral contraceptives prescribed currently showed no benefit of up to 150 mg/day of vitamin B₆ (pyridoxine) over a placebo in the prevention of side effects, such as nausea, vomiting, dizziness, depression, and irritability (16).

Premenstrual syndrome (PMS)

The use of vitamin B₆ to relieve the side effects of high-dose oral contraceptives led to the use of vitamin B₆ in the treatment of premenstrual syndrome (PMS). 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). A review of twelve placebo-controlled double-blind trials of vitamin B₆ in PMS concluded that evidence for a beneficial effect was weak (17). A more recent review of 25 studies of vitamin B₆ and PMS suggested that doses of vitamin B₆ up to 100 mg/day may be of value, but conclusions were limited by the poor quality of most of the studies evaluated (18).

Depression

Because a key enzyme in the synthesis of the neurotransmitters, serotonin and norepinephrine, is PLP-dependent, it has been suggested that vitamin B-6 deficiency may lead to depression. However, clinical trials have not provided evidence that vitamin B-6 supplementation is effective in the treatment of depression (15).

Morning sickness (nausea and vomiting in pregnancy)

Vitamin B₆ has been used since the 1940's to treat nausea during pregnancy. Vitamin B₆ was included in the medication, Bendectin, which was prescribed for the treatment of morning sickness, and later withdrawn from the market due to unproven concerns that it increased the risk of birth defects. Vitamin B6 itself is considered safe during pregnancy, and has been used in pregnant women without any evidence of fetal harm (19). The results of two double-blind placebo-controlled trials that used 25 mg of pyridoxine every 8 hrs for 3 days (20) or 10 mg of pyridoxine every 8 hrs for 5 days (19) suggest vitamin B₆ may be beneficial in alleviating morning sickness. Each study found a slight but significant reduction in nausea or vomiting in pregnant women. A recent systematic review of placebo-controlled trials for nausea of early pregnancy found vitamin B₆ to be somewhat effective (21). However, it should be noted that morning sickness also resolves without any treatment, making it difficult to perform well-controlled trials.

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. Several early studies by the same investigator suggested that vitamin B₆ status was low in individuals with carpal tunnel syndrome and that supplementation with 100-200 mg/day over several months was beneficial (22, 23). A recent study found decreased blood levels of PLP to be associated with increased pain, tingling, and nocturnal wakening, all symptoms of carpal tunnel syndrome, in men who were not taking vitamin supplements (24). Studies using electrophysiological measurements of median nerve conduction have generally failed to find an association between vitamin B₆ deficiency and carpal tunnel syndrome. While a few trials 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 (15, 25).

Sources

Food sources

Surveys in the U.S. have shown that dietary intake of vitamin B₆averages about 2 mg/day for men and 1.5 mg/day for women. A survey of elderly individuals found that men and women over 60 consumed about 1.2 mg/day and 1.0 mg/day, respectively, both less than the current RDA. Certain plant foods contain a unique form of vitamin B₆ called pyridoxine glucoside. This form of vitamin B₆ appears to be only about half as bioavailable as vitamin B₆ from other food sources or supplements. Vitamin B₆ in a mixed diet has been found to be approximately 75% bioavailable (4). In most cases, including foods in the diet that are rich in vitamin B₆ should supply enough to prevent deficiency. However, those who follow a very restricted vegetarian diet might need to increase their vitamin B₆ intake by eating food, fortified with vitamin B₆, or by taking a supplement. Some foods that are relatively rich in vitamin B₆ and their vitamin B₆ content in milligrams (mg) are listed in the table below. For more information on the nutrient content of foods you eat frequently, search the USDA food composition database.

Safety

Toxicity

Because adverse effects have only been documented from vitamin B₆ supplements and never from food sources, only the supplemental form of vitamin B₆ (pyridoxine) is discussed with respect to safety. Although vitamin B₆ is a water-soluble vitamin and is excreted in the urine, very high doses of pyridoxine over long periods of time may result in painful neurological symptoms known as sensory neuropathy. Symptoms include pain and numbness of the extremities, and in severe cases difficulty walking. 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. None of the studies, in which an objective neurological examination was performed, found evidence of sensory nerve damage at intakes of pyridoxine below 200 mg/day (15). In order 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 (see table below) (4). Because placebo-controlled studies have generally failed to show therapeutic benefits of high doses of pyridoxine, there is little reason to exceed the UL of 100 mg/day.

Drug interactions

Certain medications, interfere with the metabolism of vitamin B₆, and may result in deficiency if individuals taking such medications are not given supplemental vitamin B₆. The anti-tuberculosis medications, isoniazid and cycloserine, the metal chelator, penicillamine, and antiparkinsonian drugs, including L-dopa, form complexes with vitamin B₆, creating a functional deficiency. The efficacy of other medications may be altered by high doses of vitamin B₆. High doses of vitamin B₆ have been found to decrease the efficacy of the anticonvulsants, phenobarbitol and phenytoin, and L-dopa (2, 15).

Linus Pauling Institute Recommendation

Metabolic studies suggest that young women require 0.02 mg of vitamin B₆ per gram of protein consumed daily (3, 27, 28). Using the upper boundary for acceptable levels of protein intake for women (100 grams/day), the daily requirement for young women would be calculated at 2.0 mg daily. Older adults may also require at least 2.0 mg/day. For these reasons, the Linus Pauling Institute recommends that all adults consume at least 2.0 mg of vitamin B₆ daily. Following the Linus Pauling Institute recommendation to take a daily multivitamin/mineral supplement containing 100 % of the Daily Value for vitamin B₆ will ensure an intake of at least 2.0 mg/day of vitamin B_6. Although a vitamin B₆ intake of 2.0 mg daily is slightly higher than the most recent RDA, it is 50 times less than the tolerable upper intake level (UL) set by the Food and Nutrition Board (see Safety).

Older adults (65 years and older)

Metabolic studies have indicated that the requirement for vitamin B₆ in older adults is approximately 2.0 mg daily (29), and could be higher if the effect of marginally deficient intakes of vitamin B₆ on immune function and homocysteine levels are clarified. Despite evidence that the requirement for vitamin B₆ may be slightly higher in older adults, several surveys have found that over half of individuals over age 60 consume less than the current RDA (1.7 mg/day for men and 1.5 mg/day for women). For these reasons, the Linus Pauling Institute recommends that older adults take a multivitamin/multimineral supplement, which generally provides at least 2.0 mg of vitamin B₆ daily.

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