The possible roles of selected B vitamins in the development and progression of sarcopenia are reviewed. Age-related declines in muscle mass and function are associated with huge and increasing costs to healthcare providers. Falls and loss of mobility and independence due to declining muscle mass/function are associated with poor clinical outcomes and their prevention and management are attractive research targets. Nutritional status appears a key modifiable and affordable intervention. There is emerging evidence of sarcopenia being the result not only of diminished anabolic activity but also of declining neurological integrity in older age, which is emerging as an important aspect of the development of age-related decline in muscle mass/function. In this connection, several B vitamins can be viewed as not only cofactors in muscle synthetic processes, but also as neurotrophic agents with involvements in both bioenergetic and trophic pathways. The B vitamins thus selected are examined with respect to their relevance to multiple aspects of neuromuscular function and evidence is considered that requirements, intakes or absorption may be altered in the elderly. In addition, the evidence base for recommended intakes (UK recommended daily allowance) is examined with particular reference to original datasets and their relevance to older individuals. It is possible that inconsistencies in the literature with respect to the nutritional management of sarcopenia may, in part at least, be the result of compromised micronutrient status in some study participants. It is suggested that in order, for example, for intervention with amino acids to be successful, underlying micronutrient deficiencies must first be addressed/eliminated.

Following an introduction of the importance of folates and the rationale for seeking to estimate fractional folate absorption from foods (especially for countries not having a mandatory folic acid fortification policy), scientific papers covering the mechanisms of folate absorption and initial biotransformation are discussed. There appears (post-1983) to be a consensus that physiological doses of folic acid undergo biotransformation in the absorptive cells of the upper small intestine to 5-methyltetrahydrofolic acid (as happens for all naturally-occurring reduced 1-carbon-substituted folates). This ‘validates’ short-term experimental protocols assessing ‘relative’ folate absorption in human subjects that use folic acid as the ‘reference’ dose. The underlying scientific premise on which this consensus is based is challenged on three grounds: (i) the apparent absence of a 5-methyltetrahydrofolic acid response in the human hepatic portal vein following absorption of folic acid, (ii) the low dihydrofolate reductase activity peculiar to man and (iii) the implications derived from recent stable-isotope studies of folate absorption. It is concluded that the historically accepted case for folic acid being a suitable ‘reference folate’ for studies of the ‘relative absorption’ of reduced folates in human subjects is invalid. It is hypothesised that the liver, and not the absorptive cells of the upper small intestine, is the initial site of folic acid metabolism in man and that this may have important implications for its use as a supplement or fortificant since human liver's low capacity for reduction may eventually give rise to saturation, resulting in significant (and potentially deleterious) unmetabolised folic acid entering the systemic circulation.

Single 13C6-labelled doses of pteroylmonoglutamic acid (PteGlu; 634 nmol) or 5-formyltetrahydrofolic acid (431–569 nmol) were given to fasted adult volunteers, and the rise in total and 13C-labelled plasma 5-methyltetrahydrofolic acid metabolite monitored over 8 h by HPLC and liquid chromatography–MS. The dose-adjusted area under the curve (AUC) for total (labelled plus unlabelled) plasma 5-methyltetrahydrofolic acid following a 5-formyltetrahydrofolic acid test dose was 155 % that obtained following a PteGlu test dose. Surprisingly, an average 60 and 40 % of the total plasma 5-methyltetrahydrofolic acid response to [13C6]PteGlu and [13C6]5-formyltetrahydrofolic acid, respectively, was unlabelled; an observation never before reported. Short-term kinetics of plasma [13C6]5-methyltetrahydrofolic acid showed a slower initial rate of increase in plasma concentration and longer time to peak following an oral dose of [13C6]PteGlu compared with that for an oral dose of [13C6]5-formyltetrahydrofolic acid, while the [13C6]5-methyltetrahydrofolic acid AUC for [13C6]5-formyltetrahydrofolic acid was 221 % that for [13C6]PteGlu. These data indicate that PteGlu and 5-formyltetrahydrofolic acid, which are thought to be well absorbed (about 90 %) at physiological doses, exhibit dramatically different rates and patterns of plasma response. A limitation in the rate of reduction of PteGlu before methylation could result in slower mucosal transfer of [13C6]5-methyltetrahydrofolic acid derived from [13C6]PteGlu into the plasma. This, when coupled with an observed similar plasma clearance rate for [13C6]5-methyltetrahydrofolic acid metabolite derived from either folate test dose, would yield a comparatively smaller AUC. These findings suggest potential problems in interpretation of absorption studies using unlabelled or labelled folates where the rate of increase, the maximum increase, or the AUC, of plasma folate is employed for test foods (mainly reduced folates) v. a ‘reference dose’ of PteGlu.

The present experiment was undertaken to verify if the demand of tissues for pteroylglutamic (folic) acid, evaluated by serum clearance and urinary excretion of folates, is different between multiparous dairy cows in late gestation (five gestating dry cows, 52.6 (SD 8.4) d before parturition), and in early lactation (four lactating non-gestating cows, 18.0 (SD 5.9) d after parturition). On day 1 the cows received one intravenous (i.v.) injection of 50 μg pteroylmonoglutamic acid/kg body weight (BW). Blood samples were taken at 0, 5, 15, 30 min, 1, 2, 4, 8 and 24 h after the i.v. injection. On day 3 the cows received one intramuscular (i.m.) injection of 0.3 mg pteroylmonoglutamic acid/kg BW. Blood and urine samples, as well as urine volume, were taken at 0, 1, 2, 4, 8, 12, 24, 36 and 48 h after the i.m. injection. On days 5, 6 and 7 a daily i.m. injection of 0.5 mg pteroylmonoglutamic acid/kg BW was given in an attempt to saturate tissues with folates. Then the cows received one i.v. (day 8) and one i.m. (day 10) injection of pteroylmonoglutamic acid according to the same procedures described previously for days 1 and 3. On day 12 plasma volume was determined. Before tissue saturation, serum clearance of folates during the 24 h following an i.v. injection was similar for gestating and lactating cows but after tissue saturation serum clearance was slower for lactating than gestating cows (stage x saturation, P = 0.04). The percentage of folates excreted in urine was not affected by the physiological stage (P ≥ 0.6) or the level of tissue saturation (P ≥ 0.5). In conclusion, serum clearance and urinary excretion of pteroylmonoglutamic acid seem to support the hypothesis that, in multiparous cows, although there are no deficiency symptoms, tissue demand for folic acid is high, especially during gestation.

A variety of compounds which bind to Fe have substantial reductions in absorption when co-administered with Fe compounds. The binding of both Fe2+ and Fe3+ ions to pteroylmonoglutamic acid and the pteroylmonoglutamate dianion was examined in vitro. In dimethylsulphoxide (DMSO) alone, pteroylmonoglutamate formed a 2:1 (pteroylmonoglutamate: Fe3+ ion) complex. However, in DMSO–aqueous Bis-Tris buffer (4:1, v/v; pH 6.0) no evidence of complex formation could be seen. Likewise spectroscopic evidence was obtained for complex formation with Fe2+ ion and pteroylmonoglutamate in DMSO alone but not in the aqueous DMSO buffer. In vivo studies examined the effect of FeSO4 on pteroylmonoglutamic acid absorption in an isolated perfused rat jejunal model of nutrient absorption. The dose of pteroylmonoglutamic acid approximated a human dose of 1 mg for the rat, while the FeSO4 doses were chosen to represent 6.4 mg, 64 mg and 300 mg human doses. There was no significant effect of FeSO4 on pteroylmonoglutamic acid absorption or instability of pteroylmonoglutamic acid in vivo in the presence of FeSO4 in the rat. Although 2:1 binding of pteroylmonoglutamic acid to Fe ions could be demonstrated in DMSO alone, no binding could be demonstrated in DMSO–Bis-Tris buffer (4:1, v/v; pH 6.0). It is unlikely that there will be a significant reduction in pteroylmonoglutamic acid absorption during concurrent ingestion of Fe preparations.