Vitamin paradox in obesity: Deficiency or excess?

Abstract

Since synthetic vitamins were used to fortify food and as supplements in the late 1930s, vitamin intake has significantly increased. This has been accompanied by an increased prevalence of obesity, a condition associated with diabetes, hypertension, cardiovascular disease, asthma and cancer. Paradoxically, obesity is often associated with low levels of fasting serum vitamins, such as folate and vitamin D. Recent studies on folic acid fortification have revealed another paradoxical phenomenon: obesity exhibits low fasting serum but high erythrocyte folate concentrations, with high levels of serum folate oxidation products. High erythrocyte folate status is known to reflect long-term excess folic acid intake, while increased folate oxidation products suggest an increased folate degradation because obesity shows an increased activity of cytochrome P450 2E1, a monooxygenase enzyme that can use folic acid as a substrate. There is also evidence that obesity increases niacin degradation, manifested by increased activity/expression of niacin-degrading enzymes and high levels of niacin metabolites. Moreover, obesity most commonly occurs in those with a low excretory reserve capacity (e.g., due to low birth weight/preterm birth) and/or a low sweat gland activity (black race and physical inactivity). These lines of evidence raise the possibility that low fasting serum vitamin status in obesity may be a compensatory response to chronic excess vitamin intake, rather than vitamin deficiency, and that obesity could be one of the manifestations of chronic vitamin poisoning. In this article, we discuss vitamin paradox in obesity from the perspective of vitamin homeostasis.

Keywords: Obesity; Type 2 diabetes; Developmental origin of disease; Folic acid; Vitamin D; Niacin; Oxidative stress; Insulin resistance; Vitamin fortification

Core tip: Obesity rates have dramatically increased among the United States population, including children, since the 1980s. Considering the lag time between risk exposure and the development of child obesity, the risk must have been imposed on the whole United States population around the late 1970s. Although evidence suggests that the risk is high vitamin intake due to the update of vitamin fortification in 1974 and the implementation of the Infant Formula Act of 1980, why do obese individuals paradoxically show low levels of fasting serum vitamins? In this paper, we try to give an answer to this question based on the current understanding of vitamin homeostasis.