Keto Diets and CVD Risk: What’s the Trade-Off?

Introduction

The evidence is growing that low carbohydrate diets may be detrimental to cardiovascular health, which remains a leading cause of death in the UK, resulting in 480 deaths per day¹.

A meta-analysis, published in August 2024², has reaffirmed previous research and professional concerns regarding ketogenic diets, particularly their tendency to be higher in saturated fats, which significantly increases both total and LDL cholesterol levels^3,4.

Previous meta-analyses have assessed generic low carbohydrate diets and their impact on cardiovascular disease (CVD) risk, but these included a wide range of carbohydrate intakes; from < 50g per day (ketogenic levels) to as much as 230g per day, closer to typical dietary patterns. This variability makes it difficult to draw definitive conclusions. In contrast, the current meta-analysis focused exclusively on randomised controlled trials (RCTs) investigating ketogenic diets alone².

Study Selection

The meta-analysis included 27 RCTs, assessing the impact of ketogenic diets on CVD risk factors in subjects without chronic disease. There was significant variability between studies, including:

• Sample sizes ranged from 4 to over 300 participants
• Mean age ranged from 21 to 52 years
• Mean BMI ranged from 21 to 40
• Duration of studies ranged from 11 days to 12 months.

Ketogenic Diet Criteria

Ketogenic diets were defined as providing <50g of carbohydrates per day or <10% of total energy came from carbohydrates; equivalent to roughly 2.5 slices of bread or two small bowls of wholegrain cereals.

CVD Risk Factors Outcomes

Blood Lipids

Total cholesterol and LDL cholesterol significantly increased in the ketogenic diet group compared to higher carbohydrate diets:

• Total cholesterol mean difference (MD) +0.36mmol/L
• LDL cholesterol MD +0.35mmol/L

Triglycerides (TG) and HDL cholesterol, however, showed significant improvements:

• TG MD -0.20mmol/L
• HDL cholesterol MD +0.16mmol/L

Blood Pressure

A significant reduction in diastolic blood pressure was noted (MD -1.41mm Hg). However, no difference was observed for systolic blood pressure.

Weight & Waist Circumference

Significant reductions were observed for both weight and BMI, but no significant change in waist circumference (WC):

• Weight MD -2.59kg
• BMI MD -1.59kg/m²

Glycaemic Control

While improvements were seen in blood glucose and insulin levels, there was no significant change in HbA1c, a key marker for long-term glycaemic control.

Implications for Practice

Total and LDL cholesterol

Elevated total and LDL cholesterol, are now unequivocally established through RCTs and Mendelian studies, as causal factors in atherosclerotic CVD^5–7. Thus, lowering LDL cholesterol is a key target in primary and secondary CVD management.

Ketogenic and other low carbohydrate diets have been consistently shown to increase total and LDL cholesterol^2–4. Given that they are no more effective than other weight loss and glycaemic control interventions, which typically provide a more cardioprotective nutrient profile³, it may be prudent to steer patients away from long-term use of ketogenic diets and advice on optimising saturated to unsaturated fat ratio^3,8.

TG, HDL cholesterol, HbA1c &  Blood Pressure

The authors suggest that the reduction in triglycerides may be a result of the weight loss achieved rather than the ketogenic diet itself. Similarly, the reduction in blood glucose is to be expected in a carbohydrate-deprived state. Interestingly, there was no significant difference in HbA1c levels, which are a more reliable measure of long-term control.

HDL cholesterol did improve significantly, though there is currently no clear evidence that higher HDL levels translate into cardiovascular benefits^5,6,9–11. Diastolic blood pressure improved but this was only measured in 7 out of the 27 studies, and it is worth noting that systolic blood pressure, which is potentially a stronger predictor of CVD outcomes, showed no significant change¹².

Weight Loss Benefits

While ketogenic and low carbohydrate diets are effective for weight loss, they are no more so than other calorie-controlled diets³. Notably, waist circumference, an important CVD risk marker, especially in South Asian and Afro-Caribbean populations, did not show improvement.

Dietary Fat & Nutritional Quality

The balance between saturated and unsaturated fats, a critical determinant of blood lipid levels, was not reported in most of the studies. Additionally, key aspects of the diet, such as the intake of whole grains, viscous fibres, vegetables, nuts, oily fish, and products fortified with stanols and sterols, were not disclosed, limiting the ability to assess the overall cardioprotective quality of the diet comparisons.

Conclusion

These findings reinforce previous evidence that, while low carbohydrate and ketogenic diets may offer short-term (<12 months) benefits for weight control and glycaemic improvement, they come with potential risks to cardiovascular health.

When weighing the benefits against the risks, it is clear that the long-term negative impact on cardiovascular health should not be overlooked, particularly as ketogenic diets are no more effective than other more balanced, cardioprotective dietary regimens. Where possible, patients should be discouraged from following these diets or provided with specialised dietary advice to ensure an optimal balance of saturated and unsaturated fats and other cardioprotective foods as well as keeping animal proteins to a minimum.

References

1. BHF. Heart Statistics - UK CVD Fact Sheet. British Heart Foundation; 2024:21. Accessed February 14, 2024. https://www.bhf.org.uk/-/media/files/for-professionals/research/heart-statistics/bhf-cvd-statistics-uk-factsheet.pdf

2. Wang Z, Chen T, Wu S, Dong X, Zhang M, Ma G. Impact of the ketogenic diet as a dietary approach on cardiovascular disease risk factors: a meta-analysis of randomized clinical trials. The American Journal of Clinical Nutrition. 2024;120(2):294-309. doi:10.1016/j.ajcnut.2024.04.021

3. HEART UK. Low Carbohydrates and Ketogenic Diets. HEART UK - Nutrition Academy. June 2024. Accessed September 9, 2024. https://www.heartuk.org.uk/dietary-patterns/low-carb-and-keto-diets

4. Flanagan A, Garton L, HEART UK. Webinars: Ketogenic Diets. HEART UK - Nutrition Academy. July 2020. Accessed September 9, 2024. https://www.heartuk.org.uk/professional-resources/webinars

5. Visseren FLJ, Mach F, Smulders YM, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC). European Heart Journal. 2021;42(34):3227-3337. doi:10.1093/eurheartj/ehab484

6. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;140(11):e596-e646. doi:10.1161/CIR.0000000000000678

7. NICE. Cardiovascular disease: risk assessment and reduction, including lipid modification. Clinical guideline CG181. May 2023. Accessed September 29, 2023. https://www.nice.org.uk/guidance/cg181/chapter/Recommendations#lifestyle-changes-for-the-primary-and-secondary-prevention-of-cardiovascular-disease

8. HEART UK. Dietary fats and blood lipids. HEART UK - Nutrition Academy. June 26, 2024. Accessed August 29, 2024. https://www.heartuk.org.uk/news-and-blogs/saturated-fats

9. Kosmas CE, DeJesus E, Rosario D, Vittorio TJ. CETP Inhibition: Past Failures and Future Hopes. Clin Med Insights Cardiol. 2016;10:37-42. doi:10.4137/CMC.S32667

10. The AIM-HIGH Investigators. Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy. New England Journal of Medicine. 2011;365(24):2255-2267. doi:10.1056/NEJMoa1107579

11. HEART UK. The latest thinking on HDL cholesterol: our HEART UK update for health professionals. HEART UK - The cholesterol charity. October 7, 2020. Accessed June 24, 2024. https://www.heartuk.org.uk/educational-content/hdl-cholesterol

12. Hippisley-Cox J, Coupland C, Brindle P. Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study. BMJ. 2017;;357:j2099. doi:10.1136/bmj.j2099