A ketogenic diet is a high-fat, low-carbohydrate diet in which only 6% to 10% of daily caloric intake comes from carbohydrate and the remaining calories are derived from fat and some protein.1 This diet reduces the body’s production of the hormone insulin to promote the production of ketone bodies from fatty acids. Studies of people on ketogenic diets generally show a decrease in fasting glucose and HbA1c as well as an increase in insulin sensitivity in the first 12 months,2-4 but some studies show that they return to baseline in the long-term.5,6 Weight loss generally is associated with a decrease in HbA1C7 so it may not be the ketogenic diet, per se, that has caused the reductions in HbA1C that have been reported. Currently, there is insufficient evidence to confirm that a ketogenic diet specifically reduces blood sugar, as compared to any other diet that results in weight loss.
Studies in overweight and obese populations indicate an improvement in glycemic control with the ketogenic diet, but their results are accompanied by drastic weight loss.2-4 Goday et al. conducted a randomized clinical trial that evaluated the short-term efficacy of a very low-calorie-ketogenic diet in patients with type 2 diabetes mellitus (T2DM).2 Eighty-nine obese subjects were randomized to a very low-carbohydrate ketogenic (VLCK) diet or a low-calorie (LC) control diet for four months. After the four months, the fasting blood glucose (FBG) was significantly reduced in the VLCK group (from 136.9 at baseline to 108.9 at four months; p<0.0001), while the FBG in the LC group was not significantly changed (from 140.5 at baseline to 123.3 at four months; p=0.1821). HbA1c was also significantly reduced in the VLCK diet group when comparing baseline versus four-month measurements (6.9 ± 1.1% vs. 6.0 ± 0.7%, p<0.0001) and not in the LC group (6.8 ± 1.0% vs 6.4 ± 0.8%, p=0.1453). Furthermore, the Homeostatic Model Assessment for Insulin Resistance Index was significantly reduced to a greater extent in the VLCK diet group than the control group indicating a greater decrease in insulin resistance (p<0.05). It should be noted that this study only followed participants for four months, limiting the results to short-term benefits. These findings should be interpreted with caution, because the VLCK diet group lost significantly more weight than the control group. Average weight loss in the VLCK group was 14.7 kg compared to the weight loss in the low calorie control group of 5.05 kg (p<0.001).
Short-term studies on healthy populations are less consistent, but lean towards a beneficial effect.8-10 Urbain et al. investigated the effect of a ketogenic diet on healthy adults in a single-arm before-and-after study.9 Forty-two subjects with a body mass index of 23.9 ± 3.1 kg/m2 completed a ketogenic diet intervention. Compared to baseline, there was a significant reduction in fasting blood glucose (91.4 ± 7.3 mg/dL vs. 88.7 ± 5.3 mg/dL, p=0.009) and fasting insulin (55.3 ± 23.7 pmol/L vs. 43.0 ± 19.7 pmol/L, p=0.001). Lower fasting insulin may be associated with improved glucose tolerance.11 There was a significant weight loss of 2.0 kg (95% confidence interval [3.9 – 0.1], p<0.001), but it was smaller than weight loss experienced in obese populations.2 Therefore, the blood sugar-lowering effects reported in this study, despite the modest weight loss, support the claim that weight loss alone may not completely account for the blood glucose reduction.
A systematic review and meta-analysis by Snorgaard et al. found two trends with regards to dietary carbohydrate restriction.5 They analyzed ten high-quality randomized trials (n=1376) that compared low to moderate carbohydrate diets to high carbohydrate diets in subjects with T2DM. First, they showed that the greater the dietary carbohydrate restriction, the greater reduction in HbA1c (r=-0.85, p<0.01). Second, the analysis found that HbA1c levels returned to baseline after 12 months. The authors did not specifically state if the return to baseline occurred because the diet was no longer being followed. From the data available to them in the systematic review, the authors conclude that the superiority of the low-carbohydrate diet with respect to glucose lowering effects, may only last as long as the participants adhere to the diet, and that there may be no inherent superiority of carbohydrate-restricting diets with regards to glycemic control. Adherence to a very low carbohydrate ketogenic diet poses a challenge since it promotes significant lifestyle change from the typical diet. These authors suggest that the effect of brief or temporary reductions in glucose parameters on cardiovascular outcomes is not known.
Bueno et al. conducted a meta-analysis of 13 randomized controlled trials (n=1577) to ascertain if overweight individuals assigned to a ketogenic diet (<10% of calories from carbohydrates) achieved greater weight loss and reduction in cardiovascular risk factors over the long term (>12 months) compared to those on low-fat diets.6 The authors found significant decreases in weight loss among those the ketogenic diet and non-significant decreases in fasting glucose, HBa1C, and fasting insulin in the same group compared to those on the low-fat diet. Fewer than ten studies measured glucose, HbA1c, and fasting insulin in their analyses and the authors did not provide data on the number of participants who were still on the diet at the end of the study period in these studies specifically.
The Bottom Line
Ketogenic diets have been shown to result in significant weight loss for as long as they are followed. Weight loss is known to lower blood glucose, independent of the diet. There is insufficient evidence to conclude that a very-low carbohydrate diet is better than other weight loss diets in lowering blood glucose.
References
- Accurso A, Bernstein RK, Dahlqvist A, et al. Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: time for a critical appraisal. Nutr Metab (Lond). 2008;5:9.
- Goday A, Bellido D, Sajoux I, et al. Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. Nutr Diabetes. 2016;6(9):e230.
- Dashti HM, Al-Zaid NS, Mathew TC, et al. Long term effects of ketogenic diet in obese subjects with high cholesterol level. Mol Cell Biochem. 2006;286(1-2):1-9.
- Hussain TA, Mathew TC, Dashti AA, Asfar S, Al-Zaid N, Dashti HM. Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. Nutrition. 2012;28(10):1016-1021.
- Snorgaard O, Poulsen GM, Andersen HK, Astrup A. Systematic review and meta-analysis of dietary carbohydrate restriction in patients with type 2 diabetes. BMJ Open Diabetes Research and Care. 2017;5:e000354.
- Bueno NB, de Melo IS, de Oliveira SL, da Rocha Ataide T. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br J Nutr. 2013;110(7):1178-1187.
- Clamp LD, Hume DJ, Lambert EV, Kroff J. Enhanced insulin sensitivity in successful, long-term weight loss maintainers compared with matched controls with no weight loss history. In: Nutr Diabetes. Vol 7.2017:e282-.
- Harvey C, Schofield GM, Zinn C, Thornley SJ, Crofts C, Merien FLR. Low-carbohydrate diets differing in carbohydrate restriction improve cardiometabolic and anthropometric markers in healthy adults: A randomised clinical trial. PeerJ. 2019;7:e6273.
- Urbain P, Strom L, Morawski L, Wehrle A, Deibert P, Bertz H. Impact of a 6-week non-energy-restricted ketogenic diet on physical fitness, body composition and biochemical parameters in healthy adults. Nutr Metab (Lond). 2017;14:17.
- Greene DA, Varley BJ, Hartwig TB, Chapman P, Rigney M. A low-carbohydrate ketogenic diet reduces body mass without compromising performance in powerlifting and Olympic weightlifting athletes. J Strength Cond Res. 2018;32(12):3373-3382.
- Weyer C, Hanson R, Tataranni P, Bogardus C, Pratley R. A high fasting plasma insulin concentration predicts type 2 diabetes independent of insulin resistance: evidence for a pathogenic role of relative hyperinsulinemia. Diabetes. 2000;49(12):2094-2101.
