Vitamin B6 status and requirements in older adults.

Vitamin B6 has sometimes been referred to as a ‘vitamin without a deficiency’. Non-specific clinical symptoms and functional losses, such as compromised haem synthesis, immunocompetence and electroencephalographic (EEG) abnormalities, have been observed in experimental (depletion) studies, but ‘spontaneous’ cases of clinical vitamin B6 deficiency in man are rare (for review, see Leklem, 1991; Bender, 1992). Biochemical evidence for an inadequate vitamin B6 supply, such as low plasma pyridoxal phosphate (PLP) levels, has been reported, however, in several studies and for various groups, but especially in elderly (van der Wielen et al. 1996; Brussaard et al. 1997). Whether the higher prevalence of a marginal vitamin B6 status among elderly has indeed functional consequences, and reflects inadequate intake, or results from metabolic changes resulting in increased vitamin B6 needs, is still under debate. Depletion–repletion studies among elderly males and females by Ribaya-Mercado et al. (1991) indeed showed that more vitamin B6 was needed to normalize plasma PLP and tryptophan loading test results compared with results found in similar (earlier) studies with younger adults. Based upon these data, the panel on ‘Folate and other B-vitamins’ from the Food and Nutrition Board in the USA recently recommended a higher RDA for vitamin B6 for older adults (51+) compared with younger age groups. In this issue, Bates et al. (1999) confirm these findings of low plasma PLP in the elderly in a representative sample of British older (65+) males and females. They also measured plasma 4-pyridoxic acid (4-PA), a catabolic product of vitamin B6, and observed a clear increase of 4-PA with age, which was not solely caused by renal impairment. In this study, as in most other studies, a strong correlation between dietary vitamin B6 intake and plasma PLP was established; however, the mean intake as such was considered adequate, with only 2–3 % of individuals with intakes below the lower nutrient reference intake (LNRI). The increase in (relative) 4-PA excretion, indicative of a higher catabolic rate, has been reported earlier (e.g. Lee & Leklem, 1985), but is not found in all studies (Kant et al. 1988; Pannemans et al. 1994). In livers of ageing (female) rats, an age-related increase in pyridoxal (PL) oxidase (EC 1.2.3.8) and dehydrogenase (EC 1.1.1.107) activities has been found which may result in an increased flux of PL through this oxidative pathway (Bode et al. 1991). The availability of PL, i.e. the substrate for 4-PA formation, is regulated by the extent of PLP binding by (enzyme-) proteins. Protein-bound PLP is protected from hydrolysis by alkaline phosphatase (EC 3.1.3.1; AP). When the protein-binding capacity decreases, the pool of unbound (‘free’) PLP increases, resulting in higher PL concentrations. Two enzymes compete for substrate PL: PL-oxidase, resulting in irreversible oxidation to 4-PA, and PL-kinase (EC 2.7.1.35), resulting in (re)phosphorylation to PLP. These mechanisms explain the decrease in 4-PA excretion if protein intake is increased under conditions of an equal vitamin B6 intake. A higher protein intake will result in an increased protein turnover and protein catabolic rate associated with a subsequent increase in transaminase enzyme activity, resulting in an increase in PLP-binding capacity. Actually, 4-PA is a spill-over product, and 4-PA excretion increases when vitamin B6 supply is in excess of PLP-binding capacity. Based upon biokinetic studies in ageing rats, Bode & van den Berg (1991) speculated that the lower plasma PLP levels, and the age-associated increase in 4-PA excretion, might reflect changes in the slowly exchanging vitamin B6 body pools, i.e. in muscle PLP disposition. Approximately 80 % of the vitamin B6 body store is located in (striated) muscle tissue as PLP bound to glycogen phosphorylase (EC 2.4.1.1.). Ageing is generally associated with a decrease in lean body mass, which is mainly muscle tissue, and may consequently result in a decrease in the vitamin B6 body pool. Pannemans et al. (1994) investigated the age-dependent relationship between vitamin B6 status indicators and protein turnover by comparing the response of various vitamin B6 status indicators between a group of young (29 (SD 1) years) and elderly (70 (SD 1) years) adults fed on standardized diets containing 12 and 21 % of energy as protein respectively. Plasma PLP was significantly lower for the older, compared with the younger age group in both diet periods. Remarkably, plasma PLP levels were higher on the high-protein compared with the lower-protein diet in the older age group, while there was no effect of protein intake level on plasma PLP in the young adults. In the younger age group, 4-PA excretion indeed became lower on the highprotein diet; however, the reverse effect was seen in the elderly group. Although there was a tendency for a negative correlation between protein breakdown and plasma PLP in the elderly, correlations between protein turnover and indices of vitamin B6 status were not significant. From these data it can be concluded that there is indeed a difference in protein intake-related vitamin B6 needs whereby elderly subjects apparently need less vitamin B6 at a higher protein intake compared with the younger adults. A higher vitamin B6 catabolic rate in the elderly might thus be interpreted as indicative for an increased vitamin B6 need, but could also reflect reduced PLP-binding capacity, i.e. lower body needs. More studies are clearly needed to unravel these complex interactions between vitamin B6 biokinetics and protein turnover in the elderly. In spite of this ambiguous interpretation of the age-related changes in vitamin B6 metabolism, functional indicators suggest an apparently higher vitamin B6 need in the British Journal of Nutrition (1999), 81, 175–176 175