Increased oxidative stress appears to be a significant factor leading to insulin resistance, dyslipidaemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to type 2 diabetes (T2D). Ascorbic acid (AA) is a water soluble anti-oxidant that reduces oxidative damage at the cellular and tissue level. So, logically, AA supplementation should therefore reduce oxidate stress and lead to improvement in glycaemic control in patients with diabetes. Does it?
Logically, if you reduce oxidative stress, insulin sensitivity should improve. However, randomised control trials exploring whether AA improves glycaemic control have mixed findings. (1-4). Ashor AW et al conducted a systematic review and meta-analysis of the RCTs (5). Overall, AA did not modify glucose, HbA1c and insulin concentrations. However, in subgroup analysis, they did find AA improved glucose concentrations in patients with T2D, older individuals and if given for more than 30 days. AA had greater effects on fasting than post prandial glucose.
The latest study looking at the effect of AA on glycaemic control is an Australian study published in the Diabetes, Obesity and Metabolism this week (6). It is a randomised, cross over trial in individuals with T2D. 27 patients on oral therapy or diet were randomised to received either 500mg of ascorbic acid or placebo. Continuous glucose monitoring was used for 48 hours to monitor the post prandial glucose for 3.5 hours post prandial for the three meals. The cumulative total of 10.5 hours were compared between the groups.
Over the study period of 4 months, daily 10.5-hour postprandial glucose decreased by 36% (P < 0.01) during AA supplementation. The mean post prandial glucose was reduced by 1.1 mmol/L with AA supplementation. The duration of day spent with hyperglycaemia (>10.0 mmol/L) also significantly decrease by 2.8 hours per day with AA supplementation. The average 24-hour glucose also significantly decreased with AA supplementation but only by 0.8mmol/L. However, the HbA1c, fasting glucose and fasting insulin did not differ between the groups.
Systolic and diastolic pressure were also significantly reduced by 7mm and 5mm Hg respectively. Body composition, lipids, energy expenditure and renal and liver function were not affected by AA supplementation.
The effects of AA on glycaemic control in patients with T2D seems very impressive but is the effect clinically significant? The reduction in post prandial glucose did translate to a reduction in time with hyperglycaemia. This have potential clinical importance given that post-prandial hyperglycaemia has been considered an independent risk factor for cardiovascular disease and cardiovascular events in individuals with T2D.(7-9).
Previous studies that reported significant improvements in HbA1c after AA supplementation included more participants, enrolled participants with a higher baseline HbA1c and/or undertook AA supplementation for a longer period (10–13). Perhaps, HbA1c may be improved with a more prolonged supplementation period.
AA is an antioxidant and it is thought that the anti-oxidant effect may have decreased the oxidative stress on muscles which leads to improved peripheral glucose disposal. Perhaps, patients with T2D have a greater need for AA. Indeed, patients with T2D have been found to have lower plasma Vitamin C concentrations compared with subjects with normal glucose tolerance (14-16). There are several proposed mechanisms including:
(1) increased ascorbate excretion in those with microalbuminuria,
(2) blood glucose may compete with vitamin C for uptake into cells due to its structural similarity to the oxidised form (dehydroascorbic acid), and
(3) increased oxidative stress may deplete antioxidant stores.
AA could be useful as an adjunct in patients with T2D for better control of glucose but the clinical significance is uncertain.
Access the latest study here.
- Davison GW, Ashton T, George L, Young IS, McEneny J, Davies B et al. Molecular detection of exercise-induced free radicals following ascorbate prophylaxis in type 1 diabetes mellitus: a randomised controlled trial. Diabetologia 2008; 51: 2049–2059.
- Ellulu MS, Rahmat A, Patimah I, Khaza’ai H, Abed Y. Effect of vitamin C on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial. Drug Des Devel Ther 2015; 9: 3405–3412.
- Gutierrez AD, Duran-Valdez E, Robinson I, de Serna DG, Schade DS. Does short term vitamin C reduce cardiovascular risk in type 2 diabetes? Endocr Pract 2013; 19: 785–791.
- Klein F, Juhl B, Christiansen JS. Unchanged renal haemodynamics following high dose ascorbic acid administration in normoalbuminuric IDDM patients. Scand J Clin Lab Invest 1995; 55: 53–59.
- AW Ashor1,, AD Werner, J Lara1,, ND Willis, JC Mathers and M Siervo. Effects of vitamin C supplementation on glycaemic control: a systematic review and meta-analysis of randomised controlled trials. European Journal of Clinical Nutrition (2017) 71, 1371–1380
- Mason SA, Rasmussen B, van Loon LJC, Salmon J, Wadley GD. Ascorbic acid supplementation improves postprandial glycaemic control and blood pressure in individuals with type 2 diabetes: Findings of a randomized cross-over trial. Diabetes Obes Metab. 2019 Mar;21(3):674-682.
- Bonora E, Muggeo M. Postprandial blood glucose as a risk factor for cardiovascular disease in Type II diabetes: the epidemiological evidence. Diabetologia. 2001;44:2107-2114.
- Cavalot F, Pagliarino A, Valle M, et al. Postprandial blood glucose predicts cardiovascular events and all-cause mortality in type 2 diabetes in a 14-year follow-up: lessons from the San Luigi Gonzaga Diabetes study. Diabetes Care. 2011;34:2237-2243.
- Esposito K, Giugliano D, Nappo F, Marfella R. Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus. Circulation. 2004;110:214-219.
- Paolisso G, Balbi V, Volpe C, et al. Metabolic benefits deriving from chronic vitamin C supplementation in aged non-insulin dependent diabetics. J Am Coll Nutr. 1995;14:387-392.
- Eriksson J, Kohvakka A. Magnesium and ascorbic acid supplementation in diabetes mellitus. Ann Nutr Metab. 1995;39:217-223.
- Afkhami-Ardekani M, Shojaoddiny-Ardekani A. Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients. Indian J Med Res. 2007;126:471-474.
- Gillani SW, Sulaiman SAS, Abdul MIM, Baig MR. Combined effect of metformin with ascorbic acid versus acetyl salicylic acid on diabetes related cardiovascular complication; a 12-month single blind multicentre randomized control trial. Cardiovasc Diabetol. 2017;16:103.
- Will, J.C.; Byers, T. Does diabetes mellitus increase the requirement for vitamin C? Nutr. Rev. 1996, 54, 193–202.
- Sargeant, L.; Wareham, N.; Bingham, S.; Day, N. Vitamin C and hyperglycemia in the European prospective investigation into cancer-Norfolk (EPIC-Norfolk) study: A population-based study. Diabetes Care. 2000, 23, 726–732.
- Kositsawat, J.; Freeman, V.L. Vitamin C and A1c relationship in the National Health and Nutrition Examination Survey (NHANES) 2003–2006. J. Am. Coll. Nutr. 2011, 30, 477–483.