The metabolism of vitamin B₆ in humans and guinea pigs

Graduation date: 1978The purposes of the research presented in this thesis were: (1)\ud to determine the precision with which it is possible to measure\ud changes in vitamin B6 compounds in the blood and urine following\ud oral doses of levels of vitamin B6 (as pyridoxine) which are in the\ud range of the normal daily intake of this vitamin; (2) to compare the\ud effect of three free forms of vitamin B6 (PL, PM, PN) at these same\ud levels using the same assays; and (3) to compare the response of\ud guinea pigs to that of humans when the animals are given three free\ud forms of vitamin B6 at physiological levels.\ud The effect of small incremental doses of pyridoxine (PN)\ud (0.5 - 10 mg) and of equimolar doses of PN, pyridoxamine (PM) and\ud pyridoxal (PL) were studied in five healthy young men. On the day\ud before and during the day of the dose, the subjects were on a controlled\ud diet that supplied 1.6 mg of vitamin B6 each day. During other days of the week, the subjects were on self-selected diets.\ud Timed blood and urine samples were obtained on the day each\ud dose was administered. The parameters measured were: plasma\ud vitamin B6 (PB6), plasma pyridoxal phosphate (PLP), urinary vitamin\ud B6 (UB6) and urinary 4-pyridoxic acid (4PA). Variables reflecting\ud the response to each dose for each of these parameters were\ud calculated in two ways; (1) the percent increase of the maximal\ud post-response value over the pre-response value; and (2) the area\ud under the curve bounded by the values obtained and the times of the\ud samples.\ud For all eight of the variables so calculated, the relationship to\ud the PN doses given were linear in the 0.5 to 10 mg range. Maximal\ud levels of plasma PLP and PB6 were reached at 1/2 hr after the dose\ud for the 0.5, 1, 2, and 4 mg levels of PN. At the 10 mg level, plasma\ud B6 peaked at 1/2 hr for 3 subjects and at 1 hr for 2 subjects. Plasma\ud PLP peaked at 1 hr following the 10 mg PN dose. PB6 was much\ud more responsive to the loading doses than was PLP. The PB6:PLP\ud ratio was maximal at 1/2 hr following the doses. Maximal values of\ud urinary 4PA and UB6 were found in the first 3 hr after the dose. The\ud ratio 4PA:UB6 decreased with increasing PN dose levels and varied\ud for each collection period following the dose.\ud The same variables were calculated for the study of a comparison\ud of 19.44 μmole doses of PN, PM and PL. The PB6 peaks occurred at 1/2 hr for PL and PN, and at 1 hr for PM. The PLP\ud peaks occurred at the following times: PN, 1/2 hr; PM, 3 hr; and\ud PL, 1 hr. Maximal levels of UB6 and 4PA were reached in the first\ud three hr after the dose for all three forms. The percent increase\ud and area variables were able to distinguish between nearly all the responses\ud to the three forms of vitamin B6 administered at the 19.44\ud μmole level. The PB6 response was largest following the PL dose,\ud but the PLP levels were lower after PL than after either PM or PN.\ud The 4PA values were highest following the PL dose, indicating that\ud the PL dose was metabolized to 4PA rather than converted to plasma\ud PLP.\ud Some of the nutrient contents of the self-selected diets were\ud found to be significantly correlated with some response variables.\ud There was no relationship found between either body weight and 4PA\ud excretion on the day before the dose, or between ascorbic acid intake\ud on the self-selected diets and 4PA excretion on the day before the\ud dose.\ud Strenuous exercise was found to significantly affect plasma PLP\ud levels in subjects who had received the loading doses of PN.\ud In another study, three groups of guinea pigs were each given\ud their Recommended Dietary Allowance of vitamin B6 as PM, PL or\ud PN. The same parameters were measured as for the humans. There\ud were no significant differences between the groups of animals in body weight, organ weights (spleen, liver, kidney, brain), plasma B6 or\ud PLP, or in formed elements of the blood (hemoglobin, hematocrit,\ud white blood cells, red blood cells). Urinary 4PA and UB6 were significantly\ud higher in animals receiving PN