Myths, Artifacts, and Fatal Flaws: Identifying Limitations and Opportunities in Vitamin C Research

Abstract

Research progress to understand the role of vitamin C (ascorbic acid) in human health has been slow in coming. This is predominantly the result of several flawed approaches to study design, often lacking a full appreciation of the redox chemistry and biology of ascorbic acid. In this review, we summarize our knowledge surrounding the limitations of common approaches used in vitamin C research. In human cell culture, the primary issues are the high oxygen environment, presence of redox-active transition metal ions in culture media, and the use of immortalized cell lines grown in the absence of supplemental ascorbic acid. Studies in animal models are also limited due to the presence of endogenous ascorbic acid synthesis. Despite the use of genetically altered rodent strains lacking synthesis capacity, there are additional concerns that these models do not adequately recapitulate the effects of vitamin C deprivation and supplementation observed in humans. Lastly, several flaws in study design endemic to randomized controlled trials and other human studies greatly limit their conclusions and impact. There also is anecdotal evidence of positive and negative health effects of vitamin C that are widely accepted but have not been substantiated. Only with careful attention to study design and experimental detail can we further our understanding of the possible roles of vitamin C in promoting human health and preventing or treating disease.

The antioxidant activity of date seed: preliminary results of a preclinical in vivo study

“…Additionally, rats exhibit poor ascorbic acid absorption from the diet. This means that using ascorbic acid to maintain antioxidant function would be less essential compared to the other important functions of this nutrient (Michels and Frei, 2013). Regarding vitamin E, the wide variability noted for this parameter and the sensitivity of the method cannot be ignored.…”

High Levels of Dietary Supplement Vitamins A, C and E are Absorbed in the Small Intestine and Protect Nutrient Transport Against Chronic Gamma Irradiation

“…Vitamin C is produced endogenously in the mouse gut and dietary vitamin C is not absorbed well (35). Tsao et al showed that large increases in dietary vitamin C results in only small increases in vitamin C concentrations in brain, kidney, muscle, liver and spleen of mice (36).…”

Dietary Strategies Implicated in the Prevention and Treatment of Metabolic Syndrome

“…It is a water-soluble antioxidant mainly found in fruits, especially citrus (lemon, orange), and vegetables (pepper, kale) [120]. Several beneficial effects have been associated to this vitamin such as antioxidant and anti-inflammatory properties and prevention or treatment of CVD and type 2 diabetes [121,122,123]. …”