VITAMIN B6

Functions and essentiality Vitamin B6 is a mixture of pyridoxal, pyridoxine, pyridoxamine, and their 5'-phosphates, which are metabolically interconvertible. Pyridoxal phosphate (PLP) is a cofactor for a large number of enzymes catalysing reactions of amino acids. These are of central importance in the body's overall protein metabolism, and hence requirements are related to the total amount of amino acids to be metabolised. PLP is also the cofactor for glycogen phosphorylase. Gross clinical deficiency of vitamin B6 is rare. In the early 1950s, however, an infant milk preparation which had undergone severe heating in manufacture lost much of its pyridoxine and the infants who were fed it developed a number of metabolic abnormalities and many convulsed. The symptoms responded to vitamin B6 supplementations.


Sources The vitamin is widely distributed in foods, although much of the vitamin B6 in some vegetables may be present as unavailable glycosides. Intestinal flora also synthesise relatively large amounts, at least some of which is absorbed.


Requirements Estimates of the total body pool of Vitamin B6, based on very few studies, vary between 40-250 mg. Shane determined a half-life of 33 days for this pool, which implies an average requirement for replacement of between 0.6-3.78 mg/d. More useful estimates of vitamin B6 requirements have come from studies of changes in tryptophan and methionine metabolism, and blood vitamin B6, during depletion and repletion of adults maintained on controlled diets. Deficiency develops faster on relatively high protein intakes (80-160 g/d) than on lower intakes (30-50 g/d). During repletion of deficient subjects, tryptophan and methionine metabolism and blood vitamin B6 are normalised faster at low than at high levels of protein intake.


Adults By interpolation from the above studies, which used a relatively wide range of vitamin B6 intakes with two different intakes of protein, the Panel agreed with most other committees that the RNI for vitamin B6 is 15 /Ag/g dietary protein. With the variance of 20 per cent, the LRNI and the EAR become I 1 lAg and 13 Ag per gram of protein respectively. Because requirements will depend upon actual protein intake, the Panel considered it inadvisable to set absolute DRVs for this nutrient. If, however, the energy intake of the group was at the EARs in this Report and protein provided 14.7 per cent of this energy as in the recent dietary survey of British adultS, then the absolute RNIs would be as in Table 1.4.


Infants Of the infants fed overheated formula, 0.3 per cent convulsed when their pyridoxine intake was 60 ttg/d. Provision of 260 Agld prevented or cured these symptoms, and 300 Agld normalised tryptophan metabolism. However, those amounts overestimate infants' requirements because the pyridoxal-lysine which was formed in this formula has anti-vitamin activity. Based on the composition of pooled mature human milk, the DHSS Guidelines on Artificial Feeds for the Young Infant recommend a concentration of vitamin B6 not less than 5 AgIlOO ml and a protein concentration between 1.5-2.0 g/100 ml, which gives a vitamin B6 intake of 2.5-3.5 itg/g protein. The Panel equated this to the LRNI up to the age of 6 months, and set an RNI of 8 ug/g protein which is the amount calculated for human milk from the data of Paul and Southgate. These values are lower than for adults, in part because some of the protein is used for tissue growth rather than metabolised for energy.


Pregnancy Plasma pyridoxal phosphate falls markedly in pregnancy, but there is no evidence that it is necessary or desirable to raise the plasma PLP of pregnant women to that considered normal for non-pregnant women. Oral contraceptive users There is no evidence that use of oral contraceptive steroids increases the requirement for vitamin B6, although pharmacological doses of the vitamin may overcome some of the side-effects of contraceptive steroids.


The elderly There is a fall in plasma PLP of some 3.6 nmol/L per decade of life. It is not clear whether this represents a decline in vitamin B6 status with age, or simply a change in the blood concentration of the vitamin; erythrocyte aspartate aminotransferase activity does not show a similar change with age. Middle-aged women fed a constant diet providing 2.3-2.4 mg/d vitamin B6 show lower plasma PLP and higher urinary pyridoxic acid than young women fed the same diet. It seems likely that there are age related changes in the absorption and metabolism of the vitamin, but although the elderly may have a higher absolute requirement than younger people, there is insufficient evidence from which to quantify an increased RNI, especially as some studies have failed to show any beneficial effect of supplements as high as 20 mg/d.


Guidance on high intakes Schaumburg et al reported the development of sensory neuropathy in 7 patients taking 2-7 g/d pyridoxine. Although there was residual damage in some patients, withdrawal of these extremely high doses resulted in a considerable recovery of sensory nerve functions. Dalton and Dalton reported peripheral sensory neuropathy in 60 per cent of 172 women taking between 50-500 mg vitamin B6/d for 6 to 60 months, but even among women taking only 50 mg/d, 40 per cent reported symptoms of peripheral sensory neuropathy. Within 6 months after withdrawal of these vitamin B6 supplements, all patients reported recovery. Although one study has demonstrated no teratogenic effect of vitamin B6 in experimental animals, the safety of high intakes in human pregnancy has not been established.