ABSTRACT
Although vitamin C deficiency and scurvy are generally considered as pure nutritional disorders, only a minority of the vitamin C concentration is determined by food intake. In the presence of transition metals (iron and copper), the antiscorbutic factor shifts from an antioxidant to a pro-oxidant function. Haptoglobin (Hp) is a plasma α-2 glycoprotein characterized by 3 common phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). Its free hemoglobin (Hb)-binding capacity prevents Hb-driven oxidative damage. When the antioxidant capacity of Hp is insufficient, its role is taken over by hemopexin (heme-binding protein) and by vitamin C (free radical scavenger). The Hp 2-2 phenotype has a lower capacity to inhibit oxidation and vitamin C depletion. In this article, two consequences of this major finding are tackled. The Hp polymorphism is an important non-nutritional modifying factor in the pathogenesis of vitamin C deficiency and scurvy, which may explain the success of long-range human migration by the natural selection of some populations characterized by high Hp 1 allele frequencies. Moreover, we propose tailoring the recommended dietary allowance (RDA) values of vitamin C, taking into consideration the Hp phenotype dependency.
ABSTRACT
Ascorbic acid (vitamin C) is prone to oxidation in vivo. The human plasma protein haptoglobin (Hp) shows a genetic polymorphism with 3 major phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2) that show important functional differences. Despite an adequate nutritional supply, in Hp 2-2 individuals (most common among Asian populations) vitamin C is markedly lower in concentration and particularly prone to oxidation in vivo. Therefore, susceptibility to subclinical and clinical vitamin C deficiency (scurvy) is partly genetically determined. The genetic advantage of the Hp1 allele as a vitamin C stabilizing factor helps to elucidate the direction and successes of long-distance sea crossing human migrations in history. Clinical trials demonstrated Hp phenotype-related effects of antioxidant treatment. Because vitamin C is a first line antioxidant, Hp polymorphism and its effects on vitamin C have major clinical consequences; a marked difference in genetic susceptibility toward atherosclerosis between Hp phenotypes is attributable to variation in LDL oxidation. The classical view of vitamin C and scurvy being a pure nutritional condition needs to be updated. These findings should foster research investigating the role of Hp polymorphism in human disease, and in vitamin C deficiency and atherosclerosis in particular.
Subject(s)
Ascorbic Acid Deficiency/genetics , Ascorbic Acid/administration & dosage , Diet , Haptoglobins/genetics , Scurvy/genetics , American Indian or Alaska Native , Asian People , Gene Frequency , Genetic Predisposition to Disease , History, 16th Century , History, 17th Century , History, 19th Century , History, Medieval , Humans , Polymorphism, Genetic , Scurvy/epidemiology , Scurvy/history , White PeopleABSTRACT
BACKGROUND: Vitamin C is a powerful antioxidant (free radical scavenger). Apart from the diet, other factors regulating its catabolism may affect its serum concentration. Haptoglobin (Hp) is a plasma protein participating in iron metabolism. It shows a genetic polymorphism which shows marked geographical differences. We investigated the relationship between vitamin C, iron status and haptoglobin polymorphism in Chinese men and women. METHODS: Iron status markers were compared according to Hp phenotypes determined by chemiluminescence detection in 110 healthy Chinese subjects. The concentration of haptoglobin was determined using an immunoturbidimetric method. Serum vitamin C was tested by a 2,4-dinitrophenylhydrazine based method. RESULTS: In Chinese, the haptoglobin phenotype distribution was 10.0% Hp 1-1, 33.6% Hp 2-1, and 56.4% Hp 2-2. In the study group, serum vitamin C concentration was associated with haptoglobin type, showing lowest values in serum from Hp 2-2 subjects in males (p=0.028, ANOVA). In contrast to Hp phenotype, Hp concentration did not affect vitamin C concentration. Hp 2-2 shows higher haptoglobin (p=0.002 (ANOVA)) than individuals with the other types. Furthermore, vitamin C was influenced by (log)ferritin levels. In Chinese, vitamin C is influenced by haptoglobin polymorphism and iron status. CONCLUSION: The present findings support the role of non-nutritional factors in vitamin C status.