Vitamin B6 is the common descriptor for three compounds which depend on the metabolism of each to a coenzyme pyridoxal phosphate for their biological activity (PalP). That coenzyme plays critical roles in several aspects of metabolism, giving the vitamin importance in such diverse areas as growth, cognitive development, depression, immune function, fatigue, and steroid hormone activity (1).
Vitamin B6 deficiency occurs in free-living populations with up to 68% incidence in developed countries. Vitamin B6-deficient humans exhibit symptoms that can be quickly corrected by administration of the vitamin: weakness, sleeplessness, nervous disorders (peripheral neuropathies), and impaired cell-mediated immunity.
Behavioural differences have been associated with low vitamin B6 status: a study in Egypt found that mothers of marginal (subclinical) vitamin B6 status were less responsive to their infants’ vocalizations, showed less effective response to infant distress, and were more likely to use older siblings as caregivers than were mothers of better vitamin B6 status. In addition, studies with volunteers fed a vitamin B6-free diet or a vitamin B6 antagonist have shown increased susceptibility to infection (2). Because plasma concentrations of vitamin B6 decrease with age, it is expected that elderly people may be at greater risk of vitamin B6 deficiency than younger people (3).
Many of the signs of vitamin B6 toxicity resemble those of vitamin B6 deficiency; it has been proposed that the metabolic basis of each condition involves the tissue-level depletion (4). Doses up to 750 mg/day for extended periods of time (years) have been found safe.
Sources of Vitamin B6
Vitamin B6 is widely distributed in foods, occurring in greatest concentrations in meats, whole-grain products (especially wheat), vegetables, and nuts. In the cereal grains, vitamin B6 is concentrated primarily in the germ and one of the outer layers. Hence, the refining of grains in the production of flours, which removes much of these fractions, results in substantial reductions in vitamin B6 content. White bread, therefore, is a poor source of vitamin B6 unless it is fortified.
The chemical forms of vitamin B6 tend to vary among foods of plant and animal origin. Vitamin B6 in foods is stable under acidic conditions, but unstable under neutral and alkaline conditions, particularly when exposed to heat or light. Therefore, cooking and thermal processing tend to result in highly variable losses, with plant-derived foods, losing little, if any, of the vitamin, and animal products losing substantial amounts. Milk, for example, can lose up to 70% of its inherent vitamin B6 on drying.
The storage losses of naturally occurring vitamin B6 from many foods and feedstuffs can be substantial (25–50% within a year). Because it is particularly stable, pyridoxine hydrochloride is used for food fortification and in multivitamin supplements.
The bioavailability of vitamin B6 in most commonly consumed foods appears to be in the range of 70–80%. However, appreciable amounts of the vitamin in some foods are not biologically available (6). For example, wheat bran contains vitamin B6 in largely unavailable form(s), the presence of which reduces the bioavailability of the vitamin from other foods consumed at the same time. Bioavailability of the vitamin of plant foods tends to be greater than that of foods derived from animals. Although the microflora of the colon synthesize vitamin B6, it is not absorbed there in humans, so we derive no benefit from this microbial source of the vitamin. In contrast, ruminants benefit from their rumen microflora, which produces vitamin B6 in adequate amounts from where it is absorbed.
The greatest levels of vitamin B6 are found in the liver, brain, kidney, spleen, and muscle, where it is bound to various proteins. Muscle contains most (70–80%) of the body’s vitamin B6. Moderate exercise has been found to increase plasma concentrations substantially, e.g., by 20% within 20 minutes. This appears to be related to the increased need for gluconeogenesis. The liver is the central organ for vitamin B6 metabolism, containing all of the enzymes involved in its interconversions. Vitamin B6 status can be antagonized by alcohol and other factors that increase the rate of its degradation.
Functions of Vitamin B6
Vitamin B6 serves as an essential cofactor for several enzymes, with its metabolically active form acting as a coenzyme of more than 140 enzymes, most of which are involved in the metabolism of amino acids (7). Vitamin B6 is required cofactor for two key enzymes in the conversion of tryptophan to niacin. Vitamin B6 has two roles in gluconeogenesis. Vitamin B6 dependent enzymes also function in the biosynthesis of the neurotransmitters serotonin, epinephrine and norepinephrine, provide a source of energy for the brain, and in the synthesis of γ-aminobutyric acid (GABA) (8).
Vitamin B6 functions in the synthesis of haeme and it also binds to haemoglobin at two sites to enhance the O2-binding capacity of that protein, and inhibits the physical deformation of sickle-cell haemoglobin. Vitamin B6 is required for the biosynthesis of sphingolipids and other enzymes in phospholipid synthesis. It has been shown to modulate gene expression. Elevated intracellular levels of the vitamin are associated with decreased transcription in responses to glucocorticoid hormones (progesterone, androgens, estrogens).
Low vitamin B6 status has been associated with increased risk of coronary artery disease (9). This relationship has been linked to altered platelet aggregation. Low vitamin B6 status can cause homocysteinemia which has been associated with increased risks of occlusive vascular disease, total and cardiovascular disease-related mortality, stroke, and chronic heart failure (10). But low plasma vitamin B6 levels have also been associated with increased risk of vascular disease independent of plasma homocysteine level. A recent study suggested that treatment with high doses of vitamin B6 and folic acid were effective in reducing both plasma homocysteine and the incidence of abnormal exercise electrocardiography tests, suggesting reductions in risk of atherosclerotic disease (11).
Vitamin B6 has a key role in the synthesis of the neurotransmitters dopamine, norepinephrine, serotonin, and GABA, as well as sphingolipids and polyamines.
Vitamin B6 has a role in the support of immune competence that has not been elucidated. (12) Animal and human studies have demonstrated effects of vitamin B6 deprivation on both humoral (diminished antibody production) and cell-mediated immune responses (increased lymphocyte proliferation, reduced delayed-type hypersensitivity responses, reduced T cell-mediated cytotoxicity, reduced cytokine production), and suboptimal status of the vitamin has been linked to declining immunologic changes among the elderly, persons with human immunodeficiency virus (HIV), and patients with rheumatoid arthritis (13,14).
Vitamin B6 at relatively high doses has been reported to produce positive effects in a number of conditions affecting individuals who were not apparently deficient in the vitamin.
Sideroblastic anemia. Dosages as great as 200 mg/ day (15)
Sickle cell anemia. A small study found patients to have lower plasma B6 levels than controls, which responded to oral supplementation within 2 months.
Iron storage disease. Complexes which chelate iron have been found effective in stimulating the excretion of iron in patients with iron-storage disease.
Suppression of lactation A few studies have reported vitamin B6 as effective in suppressing lactation,
Asthma. Low circulating B6 levels have been reported in patients with asthma, and one small study found vitamin B6 treatment to reduce the severity and frequency of attacks (16).
Carpal tunnel syndrome. This disorder, involving pain and paresthesia of the hand, is caused by irritation and compression of the medial nerve by the transverse ligaments of the wrist, in ways that are exacerbated by redundant motions. The condition has been associated with low circulating levels of B6 and low erythrocyte enzyme activities. It has been suggested that such deficiencies lead to oedematous changes to and proliferation of the synovia, causing compression of the nerve in the carpal tunnel. Some investigators have reported high doses to be as effective as treatment (17).
Diabetes. Several studies have found vitamin B6 supplementation to improve glucose tolerance (18,19)
Premenstrual syndrome. This syndrome affects some 40% of women 2–3 days before their menstrual flow. It involves tension of the breasts, pain in the lumbar region, thirst, headache, nervous irritability, pelvic congestion, peripheral oedema, and, usually, nausea and vomiting. Premenstrual syndrome has been reported to respond to vitamin B6, presumably by affecting levels of the neurotransmitters, serotonin and γ-aminobutyric acid (GABA), that control depression, pain perception, and anxiety. Women experiencing premenstrual symptoms appear to have circulating B6 levels comparable to unaffected women; nevertheless, high doses of the vitamin have been found to alleviate at least some symptoms in many cases. A review of randomized clinical trials concluded that vitamin B6 is likely to be of benefit in treating these symptoms (20).
Morning sickness. A randomized clinical trial showed that the use of B6 (25 mg every 8 hours for 3 days) significantly reduced vomiting and nausea in pregnant women. However, there is no evidence that women who experience nausea and vomiting in pregnancy are of abnormal vitamin B6 status.
It has been suggested that in Alzheimer’s disease, mitochondrial cytochrome oxidase (complex IV) may be reduced and this has been observed in certain genetically confirmed states. A small study demonstrated considerable effectiveness of mitochondrial activation therapy using CoQ10, iron and vitamin B6 (21)
Vitamin B6 compounds have been shown to act as competitive inhibitors toward the oxidation of catechol derivatives and the catecholamine neurotransmitter dopamine by copper complexes that may reflect the conditions under oxidative stress in Alzheimer’s disease (22)
In a population of patients with mild to moderate AD in Taiwan, a multivitamin supplement containing vitamins B6 and B12 and folic acid for 26 weeks decreased homocysteine concentrations. (23)
In doses of 10–25 mg, vitamin B6 increases the conversion of l-dopa to dopamine which, unlike its precursor, is unable to cross the blood–brain barrier. The vitamin can thus interfere with l-dopa in the management of Parkinson’s disease; it should not be administered to individuals taking l-dopa without the concomitant administration of a decarboxylase inhibitor.
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Keywords-pyridoxine, diabetes, premenstrual syndrome, morning sickness, cardiovascular disease, immunity, anaemia, asthma, pregnancy, carpal tunnel syndrome. Alzheimer’s disease, parkinson’s disease