Deeper Dive: Investigating the relationship between vitamin C, type 2 diabetes, and heart disease

Type 2 diabetes mellitus (T2DM) is characterized by elevated glucose (hyperglycemia), insulin resistance, and failure of insulin-secreting pancreatic beta cells^[1] (seen as relative insulin deficiency and pancreatic inflammation and destruction^[2]). T2DM is associated with obesity^[2], oxidative stress^[3], systemic inflammation^[4], and heart disease. About 2 in 3 people with T2DM are insufficient or deficient in vitamin C, compared to about 1 in 4 people with normal glycemia, even if the people with T2DM are consuming enough vitamin C, according to one study^[5] of 89 people. Across most studies, vitamin C levels are at least 30% lower among people with T2DM^[6]. Mechanistically, vitamin C’s role in ameliorating aspects of T2DM also makes some sense. Some of the pathways by which it may help are laid out in Figure 1.

Figure 1: Some ways in which vitamin C may help dampen the impact of diabetes

References: Ellulu et al. Drug Des Devel Ther. 2015 Jul.^[7]
Newsholme et al. Am J Physiol Cell Physiol. 2019 Sep.^[8]
Will et al. Nutr Rev. 1996 Jul.^[6]
Crabbe et al. Prog Retin Eye Res. 1998 Jul.^[9]
Yan. Animal Model Exp Med. 2018 Mar.^[10]
Haidara et al. Curr Vasc Pharmacol. 2006 Jul.^[11]
Krone et al. Med Hypotheses. 2004.^[12]
Taddei et al. Circulation. 1998 Jun.^[13]
Mortensen et al. Nitric Oxide. 2014 Jan.^[14]

Vitamin C supplementation has been associated with some improved glycemia outcomes (blood glucose, HbA1c, serum insulin, and insulin resistance) in previous meta-analyses, but results have been inconsistent. A 2011 systematic review and meta-analysis looking at the effect of supplementation with vitamin C and/or E on T2DM showed no effect on glucose or insulin and a small lowering effect on HbA1c. A 2014 meta-analysis of observational and randomized controlled trials showed a significant effect of vitamin C on decreasing fasting blood glucose, but no effect on HbA1c^[15]. In this analysis, vitamin C was associated with lower levels of some oxidative stress markers, but was not associated with HbA1c or glucose outcomes. The most recent meta-analysis showed that, overall, vitamin C did not modify glucose, HbA1c or insulin concentrations^[16]. Looking at subgroups in this study showed that vitamin C may have a more pronounced effect on fasting insulin than on post-meal insulin levels, on people diagnosed with T2DM than on people without a diagnosis, and when the duration of intervention was longer rather than shorter.

Other meta-analyses have focused on heart health measures related to T2DM. One 2012 meta-analysis concluded that vitamin C lowers blood pressure in all populations, and suggested that its effect on diastolic blood pressure may be greater for people with T2DM than for people without^[17] T2DM. More recently, a meta-analysis looking at the effect of vitamin C on markers of endothelial function showed a strong beneficial relationship^[18]. Finally, a 2016 meta-analysis looking exclusively at blood lipids found no significant effect of vitamin C^[19].

None of these systematic reviews and meta-analyses assessed the certainty of evidence. With 10 new studies published since the previous 2017 systematic review on vitamin C and glycemic control, the present study was designed to clarify the risk of bias and update earlier estimates of vitamin C’s effect on T2D.

Some evidence suggests that vitamin C supplements may have positive effects on multiple aspects of diabetes, but the results of previous systematic reviews are mixed. Putative benefits include improvements of glycemia, blood lipids, and blood pressure. The most recent reviews of vitamin C’s effects on glycemic control and on blood lipids reported no significant associations.