Elsevier

Medical Hypotheses

Volume 62, Issue 2, February 2004, Pages 275-279
Medical Hypotheses

Ascorbic acid, glycation, glycohemoglobin and aging

https://doi.org/10.1016/S0306-9877(03)00313-XGet rights and content

Abstract

The glycation of proteins alters both their structure and function. These changes have been linked to diabetic disorders and aging. The glycation of hemoglobin is also used as a diagnostic tool; the extent of glycation being a reflection of blood glucose averaged over a two to three month period. Accurate measures of average blood sugar (e.g., glycohemoglobin (GHb)) are important in clinical management of diabetes, pregnancy, cancer, etc. Ascorbic acid (AA) can react with proteins, including hemoglobin, and possibly interfere with GHb measurements. Past reports on the impact of AA on in vivo glycation have been equivocal. We studied GHb in subjects supplementing up to 20 g AA daily and found that for each 30 μmol/L increase in plasma AA, GHb was reduced by ∼0.1. These results suggest that high AA intake can depress glycation, reduce GHb and lead to a clinically relevant underestimation of average blood sugar. Because AA is the most commonly consumed dietary supplement, awareness of an AA-associated bias in GHb is imperative. Of even broader significance is the possibility of AA-mediated inhibition of glycation in all proteins and the implications for aging. Moreover, AA could contribute through several other mechanisms to slowing of human aging (e.g., antioxidant properties, acceleration of pentose phosphate pathway, replacement of structural proteins).

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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