The Regulation of Dietary Iron Bioavailability by Vitamin C: A Systematic Review and Meta-Analysis

Abstract

Iron deficiency is the most common nutritional deficiency worldwide, in part due to the inherent low bioavailability of dietary iron (1) . Although dietary components such as vitamin C have been demonstrated to influence iron bioavailability, with the discovery of hepicidin as the hormone central regulator of iron homeostasis (2) , their significance has been questioned. Specifically, the Scientific Advisory Committee in the UK has stated that only the consumption of a healthy balanced diet is required for adequate iron status and the role of dietary enhancers is minimal (3) . Therefore, the aims of this systematic review and meta-analysis were to determine the effect of vitamin C on nonheme iron absorption and the effects of long term supplementation on iron status.The review was conducted by independent reviewers in accordance with PRISMA guidelines and is registered at Prospero (CRD42014010453). Medline, Scopus and Cochrane databases were searched from inception through to December 31 st 2016, with a basic search strategy of "(iron OR ferritin OR haemoglobin) AND (ascorbic acid OR ascorbate OR vitamin C)". Short-term (<4 weeks) and long-term trials (>4 weeks) reporting measures of iron absorption from isotopically labelled iron meals with and without vitamin C or changes to biomarkers of iron status with vitamin C supplementation in healthy adults were included. Meta-analyses were executed in Review Manager 5 software (version 5.3).From a total of 4830 identified records, 26 studies (20 short-term, 6 long-term) were included in qualitative synthesis and 22 were included in the meta-analysis (3 excluded as reported arithmetic not geometric means, 1 excluded for not reporting variance). All of the short-term studies were a 16-day crossover design, where the same iron test meals were labelled with different isotopes and consumed on consecutive mornings with and without ascorbic acid; with washout in between. The combined pooled effects showed a highly significant increase in % iron absorption when ascorbic acid was added to test meals and the l 2 statistic quantifying the level of heterogeneity, indicated a very low level of inconsistency (MD: 5·87; 95 % CI 4·43, 7·31; P = 0·00001; n = 315 total study participants; l 2 = 14 %). The effect of long-term ascorbic acid supplementation on haemoglobin status was assessed in 5 studies, arranged in descending order of haemoglobin (Hb) level (g/L) which ranged from 146 g/L-101 g/L (Fig. 1). These data show ascorbic acid supplementation increased haemoglobin value levels from baseline to follow-up significantly, (MD: 8·26; 95 % CI 3·00, 13·53; P = 0·002; n = 118 total study participants; l 2 = 58 %), with a moderate level of inconsistency between studies.We conclude, ascorbic acid enhances the absorption of nonheme iron and can increase biomarkers of iron status overtime. Increasing vitamin C intake from food or supplementation remains a practical measure to reduce the risk of iron deficiency and to moderate the incidence of iron deficiency anaemia.

Insufficient Vitamin C Levels among Adults in the United States: Results from the NHANES Surveys, 2003–2006

“…Poverty to Income Ratio (PIR): Poverty to Income Ratio information was collected in the Demographic Questionnaire. NHANES calculated PIR using Department of Health and Human Services poverty guidelines to determine qualification for financial assistance for federal aid programs such as Food Stamps, the National School Lunch Program [23]. The variable was recoded into categorical values of: High PIR (participants below 30% of the poverty line eligible for government assistance, or ≤$25,000 per year), Medium PIR (considered middle class with a household income of $25-$75,000 per year), and Low PIR (considered high-income earners with household incomes of >$75,000 per year).…”

“…Although a comprehensive list of its full benefits has still not been clearly identified, many of its valuable properties are believed to be the result of its ability to act as an electron donor [18][19][20]. These include neutralizing free radical oxygen species, inhibition of low-density lipoprotein (LDL) oxidation [21], alleviating chronic inflammation [12], supporting growth and development of healthy gut microbiota [9], enhancing neutrophil motility [10,11], aiding the proliferation of natural killer cells [12], recycling Vitamin E [22,23], and enhancing the bioavailability of iron [24]. The benefits of Vitamin C in specific epigenetic inflammatory pathways, including the ability to act as a cofactor to both start and complete DNA and histone demethylations, is being realized [25][26][27][28].…”

Vitamin C Plasma Levels Associated with Inflammatory Biomarkers, CRP and RDW: Results from the NHANES 2003–2006 Surveys

“…As a water-soluble vitamin that humans cannot endogenously synthesize, bodily vitamin C levels rely on a consistent dietary intake of various fruits and vegetables. It is a well-known antioxidant with multiple beneficial properties in the immune system including recycling and enhancing the bioavailability of other vitamins and minerals [ 1 ], influencing DNA and histone demethylation and enzyme-dependent biosynthesis of various biomolecules [ 2 , 3 ] alleviating inflammation [ 4 ], and stabilizing the structure of collagen [ 5 , 6 ]. Vitamin C has shown potential effectiveness in the treatment of severe coronavirus disease 2019 (COVID-19) and sepsis when given to patients intravenously in the intensive care setting [ 7 , 8 , 9 ].…”

Subclinical Vitamin C Plasma Levels Associated with Increased Risk of CAD Diagnosis via Inflammation: Results from the NHANES 2003–2006 Surveys

“…It is known to enhance immune cell transport and functions while simultaneously lessening overactive immune responses [ 3 ]. Multiple benefits of vitamin C include collagen synthesis [ 4 ], reusing and enhancing other vitamins and minerals [ 5 ], and influencing epigenetic processes [ 6 ]. The ability of vitamin C to donate electrons explains many of its important functions [ 7 ].…”