|Johnson, Elizabeth - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Vishwanathan, Rohini - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Rasmussen, Helen - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Lang, John - University Of Texas|
Submitted to: Molecular Vision
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/9/2014
Publication Date: 9/11/2014
Citation: Johnson, E.J., Vishwanathan, R., Rasmussen, H., Lang, J.C. 2014. Bioavailbility of AREDS1 micronutrients from softgels and tablets: a pilot study. Molecular Vision. 20:1228-1242.
Interpretive Summary: The benefit of antioxidant nutrients for slowing progression to advanced stages of age-related macular degeneration (AMD) was supported by recent clinical trials. How nutrient supplements are made can influence the amount of nutrient that is absorbed into the body. The objective of the study was to explore the influence of dosage form on the body's ability to absorb the five nutrients (zinc, copper, beta-carotene, and vitamins E and C) important for eye health. The study investigated absorption of a single dose of these nutrients in either four tablets or two softgels at the full dose level or one softgel at the half-dose level. Absorption of each micronutrient was measured based on the appearance in blood after intake of the tablets or softgels. The relative amount of nutrients that was absorbed was greater for the smaller dose (one vs. two capsules) but not enough to reach the level achieved by the full dose of either four tablets or two softgels. Vitamin C was absorbed better in the softgel formulation. Beta-carotene and vitamin E ingredients were absorbed better from the tablets. The results suggest that the formulation of a nutrient supplement can influence the amount of nutrient absorbed into the body. With the recognition of global and population-specific nutrient deficiencies, notably in the elderly populations afflicted with AMD, establishing efficient means of supplementation is of interest.
Technical Abstract: Purpose: The benefits of antioxidant micronutrients in slowing progression to advanced stages of age-related macular degeneration (AMD) was supported by the 4/day tablet form investigated in the Age-related Eye Disease Study 1 (AREDS1) and the 2/day softgel form in the Age-related Eye Disease Study 2 (AREDS2). However, the choices of excipient, dosage form, and ingredient chemistry as well as the patient physiologies and pathologies can influence bioavailability and efficacy. The objective of the study was to explore the influence of dosage form on the bioavailability of the five primary AREDS1 and Tier-2 AREDS2 micronutrients: the metals zinc and copper, beta-carotene, and vitamins E and C. The intent was to establish by chemical analysis the relative bioavailabilities of these five micronutrients in plasma, or serum for the metals, as well as to identify any opportunities for improvements. Methods: A total of 15 healthy men (5) and women (10) were recruited for a controlled, randomized, three-arm, crossover trial of the AREDS1 micronutrients. The study investigated responses in bioabsorption to a single dose of either four tablets or two softgels at the full dose level, or one softgel at the half-dose level. The bioavailability of each micronutrient was based on the pharmacokinetic profiles established through 15 samplings for each ingredient/dosage form in plasma/serum over the course of one week. Results: Bioavailability was estimated using model-independent and model-dependent procedures. A statistical advantage of the dosage form was observed in only two cases from the exaggerated effects using the half-dose softgel and for the tablet dosage form for beta-carotene and vitamin E. An unanticipated complexity was suggested by the bimodal absorption of zinc. For these micronutrients, no disadvantage (though potential advantage) was inferred for the water-soluble components presented in a softgel formulation. Increased fractional absorption was observed for the smaller dose (one capsule versus two), but it was not sufficient to reach the level achieved by the full dose of either four tablets or two softgels. A model-dependent analysis permitted an estimation of the percentage of micronutrients absorbed, with zinc, the single most important ingredient, absorbed at about a 10% level. Conclusions: The results suggest modestly contradictory requirements in the dosage form for water-soluble and lipid-soluble ingredients, as based on a goal of improved bioavailability. Comparative consistency in bioavailability was observed across dosage forms, and most nutrients between AREDS1 and AREDS2 (full dose) formulations relative to the significant variations observed within this controlled population. The results emphasize the importance of defining the requisite bioavailability of each micronutrient and the influence of the dosage form that provides it. With the recognition of global and population-specific micronutrient deficiencies, notably in the elderly populations afflicted with AMD and their significant metabolic and health consequences, establishing efficient means of supplementation are of continuing epidemiologic interest.