A ketogenic diet is a style of food intake that reduces blood levels of the hormone insulin, which in turn promotes the production of ketone bodies from fatty acids.1 The diet consists of a very high fat content (upwards of 90%) and low protein and carbohydrate content. Studies of its impact on cholesterol show inconsistent trends overall, demonstrating the need for more high-quality, long-term randomized trials that control for weight loss.2-3,5-17 However, there are some noticeable patterns within different populations. First, a ketogenic diet may lower cholesterol levels among obese individuals, but this result may be due to weight loss rather than the diet itself.1-2 Second, among non-overweight and non-obese individuals, there appears to be a short-term spike in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C).5-13 However, long-term effects are not well-supported.14-17 Some studies show that these cholesterol levels stay elevated while others show no significant change overall.
Short-Term Effects of Ketogenic Diet in Obese and Overweight Individuals
A few studies have shown a decrease in cholesterol among overweight and obese patients following a ketogenic diet.2-3 Dashti et al.2 selected 66 healthy obese individuals, where 35 had elevated cholesterol, and 31 had normal cholesterol. All were assigned a ketogenic diet. Compared to baseline, individuals in the high cholesterol group found significant reductions in TC of 29.2% (95% confidence interval [CI] [32.3 – 26.1], p<0.0001) and LDL-C of 33.5% (95% CI [40 – 27], p<0.0001). Individuals in the normal cholesterol group also had significant reductions in TC of 6.2% (95% CI [11.9 – 0.5], p=0.0170) and LDL-C of 21.3% (95% CI [28 – 14.6], p<0.0001). However, the study findings must be interpreted with caution as the lowered cholesterol levels may be a result of weight loss. During this 56-week period, there was a significant reduction in percentage average weight in the high cholesterol group of 25.8% (± 6.7%) and the normal cholesterol group of 26.0% (±5.8%). According to the 2013 overweight and obesity management guidelines by the American Heart Association, the American College of Cardiology, and The Obesity Society, there is a dose-response relationship between the amount of weight loss and improvement in lipid profile in overweight or obese adults, regardless of the specific lifestyle intervention used to achieve the weight loss.4 The substantial weight loss may have accounted for the net reduction of cholesterol in this study.
Another study was designed to control for weight loss in obese and overweight men.5 Rosenbaum et al. conducted a study on 17 overweight and obese men measuring the metabolic effects of an isocaloric ketogenic diet. The patients lived at inpatient metabolic units where all of their food was provided for the duration of the study. Following four weeks of a baseline diet (15% protein, 50% carbohydrate, 35% fat), subjects were switched to four weeks of isocaloric ketogenic diet (15% protein, 5% carbohydrate, 80% fat). After four weeks on the ketogenic diet, there was a small but significant reduction in weight (87.4 + 15.4 kg vs. 85.1 kg + 14.6, p<0.001). Analyzing the cholesterol levels during the ketogenic diet and the baseline diet, the authors found an increase in TC of 9 mg/dL (95% CI [3.3 – 14.7], p=0.009) and LDL-C of 26 mg/dL (95% CI [17 – 35], p<0.001) during the ketogenic diet. Compared to the previous study where there was a drastic weight loss and a significant reduction in cholesterol,2 this study found minimal weight loss and an increase in cholesterol.
Short-Term Effects of Ketogenic Diet in Non-Obese Individuals
In contrast, studies on non-obese populations consuming a ketogenic diet have shown at least a short-term increase in TC and LDL-C.6-8 In a before-and-after comparison study conducted by Urbain et al., the authors assessed the impact of a non-energy restricted ketogenic diet on 42 healthy adults with a BMI of 23.9 + 3.1 kg/m2 for a six-week period.6 When compared to baseline, the study found a significant increase in TC (186.5 ± 34.7 mg/dL vs. 195.3 ± 34.7 mg/dL, p= 0.019) and LDL-C (110.9 ± 31.3 mg/dL vs. 122.8 ± 33.6 mg/dL, p=0.001) at six weeks. There was also a significant mean weight loss of 2.0 kg (95% CI [2.58 – 1.43], p<0.001).
Studies among epileptic patients, in which weight was often maintained, show that TC and LDL-C are significantly increased.9-13 A study by Kwiterovich et al. examined a cohort of 141 children with difficult-to-control seizures who were assigned high-fat ketogenic diets.8 The diet was constantly adjusted to maintain an ideal weight. After six months, the researchers found a significant rise in the concentrations of TC of 58 mg/dL (95% CI [44 – 72], p<0.001) and LDL-C of 50 mg/dL (95% CI [38 – 62], p<0.001) compared to baseline. At the baseline, 51% of the patients had acceptable TC levels, but after six months, only 22% were in the acceptable range. For LDL-C, 75% of the patients had acceptable levels at baseline, but the percentage decreased to 28%.
Long-Term Effects of Ketogenic Diet
There is some evidence that cholesterol effects of a ketogenic diet may diminish over time.14-17 Saslow et al. conducted a randomized control trial among 34 overweight and obese adults with type 2 diabetes or prediabetes. Participants were randomly assigned to a low-carbohydrate ketogenic diet (LCK) or a moderate-carbohydrate, calorie-restricted, low-fat diet (MCCR). LCK participants reduced their carbohydrate intake to between 20 – 50 g a day, while the MCCR derived 40 – 50% of their calories from carbohydrates and reduced intake by 500 kilocalories per day. After six months, the LDL-C was significantly higher in the LCK group, but at twelve months, there was no longer a significant difference. These findings must be interpreted with caution, because the LCK group lost significantly more weight than the MCCR group, making it unclear if reduction was due to weight loss. Also, adherence to the LCK diet was monitored by measurements of blood ketone levels, but only for the first few months of the intervention.
A study by Heussinger et al. suggests a similar trend in a cohort of 10 non-obese patients with glucose transporter type 1 deficiency syndrome.17 These patients followed a ketogenic diet for at least 10 years, with a follow-up every six to twelve months. When comparing the patients’ lipid profiles after several time markers, the authors found a decrease in TC at six months with a standard deviation score of -0.51 (p=0.048) and LDL-C at two years with a standard deviation score of -0.19 (p=0.06). After these respective time intervals, TC and LDL-C levels were no longer significantly different. However, the patients in this small study may not be representative of the general population.
The Bottom Line
The data on the impact of a ketogenic diet on cholesterol is inconsistent and vary by the population and duration of the study. Multiple studies suggest that there is a short-term increase in total cholesterol and LDL-cholesterol for non-obese populations. Ultimately, more long-term randomized controlled trials on larger study populations are needed before more substantial claims can be made.
- Peterman M. The ketogenic diet in the treatment of epilepsy: a preliminary report. Am J Dis Child. 1924;28(1):28-33.
- 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.
- Dashi HM, Mathew TC, Hussein T, et al. Long-term effects of a ketogenic diet in obese patients. Exp Clin Cardiol. 2004;9(3):200-205.
- Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014;129(25 Suppl 2):S102-138.
- Rosenbaum M, Hall KD, Guo J, et al. Glucose and lipid homeostasis and inflammation in humans following an isocaloric ketogenic diet. Obesity. 2019;27(6):971-981.
- 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(1).
- Harvey CJDC, 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. 2019;7.
- Zajac A, Poprzecki S, Maszczyk A, Czuba M, Michalczyk M, Zydek G. The effects of a ketogenic diet on exercise metabolism and physical performance in off-road cyclists. Nutrients. 2014;6(7):2493-2508.
- Kwiterovich JPO. Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children. Jama. 2003;290(7):912.
- Zamani GR, Mohammadi M, Ashrafi MR, et al. The effects of classic ketogenic diet on serum lipid profile in children with refractory seizures.Acta Neurol Belg. 2016;116(4):529-534.
- Coppola G, Natale F, Torino A, et al. The impact of the ketogenic diet on arterial morphology and endothelial function in children and young adults with epilepsy: A case–control study. 2014;23(4):260-265.
- Özdemir R, Güzel O, Küçük M, et al. The effect of the ketogenic diet on the vascular structure and functions in children with intractable epilepsy. Pediatr Neurol. 2016;56:30-34.
- Güzel O, Yılmaz U, Uysal U, Arslan N. The effect of olive oil-based ketogenic diet on serum lipid levels in epileptic children. Neurol Sci. 2016;37(3):465-470.
- Saslow LR, Daubenmier JJ, Moskowitz JT, et al. Twelve-month outcomes of a randomized trial of a moderate-carbohydrate versus very low-carbohydrate diet in overweight adults with type 2 diabetes mellitus or prediabetes.Nutr Diabetes. 2017;7(12).
- Mohorko N, Černelič-Bizjak M, Poklar-Vatovec T, et al. Weight loss, improved physical performance, cognitive function, eating behavior, and metabolic profile in a 12-week ketogenic diet in obese adults. Nutr Res. 2019;62:64-77.
- Kapetanakis M, Liuba P, Odermarsky M, Lundgren J, Hallböök T. Effects of ketogenic diet on vascular function. Eur J Paediatr Neurol. 2014;18(4):489-494.
- Heussinger N, Marina AD, Beyerlein A, et al. 10 patients, 10 years – Long term follow-up of cardiovascular risk factors in Glut1 deficiency treated with ketogenic diet therapies: A prospective, multicenter case series. Clin Nutr. 2018;37(6):2246-2251.