The effect of graded doses of D-isoascorbic acid (IAA) on the tissue content of ascorbic acid (AA) in guinea pigs administered a marginal intake of ascorbic acid was studied. Thirty guinea pigs (inbred Hartley-strain) were randomly assigned to three equally sized treatment groups: 1) 1 mg AA (only); 2) 1 mg AA + 20 mg IAA, or 3) 1 mg AA + 100 mg IAA. Ascorbic acid alone or in combination with IAA was orally administered daily to all animals over 42 consecutive days, after which time the animals were sacrificed. Over the study period, animals dosed with 1 mg AA plus 100 mg IAA had a higher I ate of weight gain than those dosed with 1 mg AA or 1 mg AA + 20 mg IAA. Tissue concentrations of AA, IAA, and their oxidized forms, dehydroascorbic acid (DHAA) and dehydroisoascorbic acid (DHIAA) were determined by high-pressure liquid chromatography equipped with an electrochemical detector. In guinea pigs dosed with either 20 or 100 mg IAA, AA levels in the plasma, brain, liver, adrenals, lungs, kidneys, spleen, and heart were significantly decreased (P < 0.05) compared with the non-supplemented group. IAA content in the guinea pig tissues increased progressively after incremental dosing with IAA. DHAA levels decreased significantly in guinea pigs dosed with 20 mg IAA or 100 mg IAA compared with the corresponding controls in all tissues examined. Thus, in guinea pigs, the co-administration of graded levels of IAA with a marginal AA intake resulted in a decreased bioavailability of AA. (C) Elsevier Science Inc. 1997.