Ascorbic acid, glycation, glycohemoglobin and aging
Section snippets
Protein glycation and ascorbic acid
In 1987, Cerami et al. [1] summarized the interaction of glucose with protein and its association with human aging and diabetic disorders. Much additional research in the intervening years has expanded our knowledge of glycation and its effects on structure and function of various tissues (skeletal muscle, ocular lens, skin, nerves, arteries, etc.) and on individual proteins (e.g., collagen, elastin, crystallin, myosin, etc.) e.g., [2], [3], [4], [5]. The changes seen in glycosylated structural
Glycation of hemoglobin as a model
Studying glycation of the protein hemoglobin can serve as a model for in vivo protein glycation in general. The glycation of hemoglobin is used as the basis for a common diagnostic test. Blood glycohemoglobin (GHb) concentration is an integrated measure of plasma glucose that is intended to represent glucose concentrations in blood averaged over a 2–3 month period. GHb is expressed as a percentage of total hemoglobin. Hyperglycemia is a major risk factor for cardiovascular disease, cancer,
Ascorbic acid supplementation and decreased glycation
More than 11% of adults in the western United States take an individual AA supplement daily and it is the most commonly consumed nutritional supplement after multivitamins [29]. In light of this and the importance of adequate AA intake and blood glucose (BG) control in many aspects of human health including immunity, aging, birth defects, diabetes, etc., the uncertainty regarding the influence of AA on GHb mandated investigation.
Our results from a pilot study of 138 subjects who were
Consequences of underestimation of glycohemoglobin
Sargent et al. [28] found a decrease in GHb of about 0.1 for every 20 μmol/L rise in plasma AA. Our results indicated a decrease of 0.07 for a 20 μmol/L increase in plasma AA. The subjects in our study encompassed a much wider range of AA intakes and plasma AA than the population studies. In supplementing humans, a 1 g oral dose of AA can raise plasma AA to 130 μmol/L within an hour and such doses at intervals of about 2 h throughout the day can maintain ∼230 μmol AA/L [32]. A higher and more
Conclusions
Our data suggest that the inverse relationship of GHb and plasma AA extends over a wider range of GHb, plasma AA and AA intake than reported previously. It also is consistent with the concept that AA is decreasing glycation and genuinely lowering GHb. This would mean that average blood sugar, as measured by GHb, may be underestimated in subjects consuming multi-gram doses of AA. Accurate knowledge of average blood sugar (i.e., a “true” unbiased GHb) is important in cancer, diabetes, prevention
Acknowledgements
This study was supported in part by Northwest Oncology Foundation and Applied Research Institute. We thank Pierce Chemical Company for the Glycotest Kits; Professor D.H. Read and S. Belcher at Seattle University for blood assays; and H. F. Krone for manuscript preparation. Glenn A. Warner, MD, of NW Oncology Clinic is gratefully acknowledged for overseeing the study subjects.
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