Efficacy and safety of a very low-calorie ketogenic diet (VLCKD) in patients with overweight and obesity: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

XIAO Yanmei ,  XUE Kun , DANG Zhengyi , WANG Menghao , HE Gengsheng , GUO Hongwei

Department of Nutrition and Food Hygiene, School of Public Health, Fudan University, Shanghai 200032, P. R. China;

Corresponding?author：

XUE Kun, Email: xuekun@shmu.edu.cn

Keywords：

Very low-calorie ketogenic diet; Obesity; Overweight; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.202110090

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To systematically review the efficacy and safety of a very low-calorie ketogenic diet (VLCKD) in patients who were overweight or obese. Methods From inception to August 2021, the electronic databases PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, WanFang Data, VIP, and CBM were searched for randomized controlled trials (RCTs) of VLCKD in patients with overweight or obesity. Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias of the included studies. Then, meta-analysis was performed using Stata 16.0 software. Results A total of 5 RCTs involving 245 patients were included. Among patients with baseline body mass index (BMI) ≥30 kg/m², the meta-analysis showed that compared with the control group, VLCKD could significantly reduce the BMI (MD=?0.24, 95%CI ?0.39 to ?0.08, P<0.05), weight (MD=?7.00, 95%CI ?10.48 to ?3.53, P<0.05) and waist circumference (MD=?7.40, 95%CI ?12.68 to ?2.12, P<0.05) . The subgroup analysis results showed that compared with the control diet, VLCKD could significantly reduce the glucose (MD=?9.60, 95%CI ?17.52 to ?1.69, P<0.05), glycated hemoglobin (MD=?0.24, 95%CI ?0.39 to ?0.08, P<0.05), insulin resistance index (MD=?0.90, 95%CI ?1.08 to ?0.73, P<0.05) and triglycerides (MD=?41.42, 95%CI ?53.78, ?29.06, P<0.05) in patients with type 2 diabetes and with obesity or overweight. In patients with obesity or overweight, VLCKD could increase high-density lipoprotein cholesterol (MD=8.60, 95%CI 0.17 to 17.03, P<0.05) when the intervention lasted longer than 12 months. In patients with obesity or overweight, VLCKD had no effect on insulin, total cholesterol, low-density lipoprotein, urea, creatinine, or uric acid. Patients with VLCKD had a higher rate of adverse events than those in the control groups; however, there was no significant difference in the rate when the intervention lasted longer than 4 months. Conclusion The current evidence shows that VLCKD can reduce BMI, weight, and waist circumference and reduce fasting glucose, HbA₁c, insulin resistance index, and triglycerides among patients with type 2 diabetes and with obesity or overweight. However, VLCKD has no effect on insulin, total cholesterol, low-density lipoprotein, urea, creatinine, or uric acid. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.

Citation： XIAO Yanmei, XUE Kun, DANG Zhengyi, WANG Menghao, HE Gengsheng, GUO Hongwei. Efficacy and safety of a very low-calorie ketogenic diet (VLCKD) in patients with overweight and obesity: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2022, 22(4): 403-410. doi: 10.7507/1672-2531.202110090 Copy

1.	Global BMI Mortality Collaboration None, Di Angelantonio E, Bhupathiraju ShN, et al. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet, 2016, 388(10046): 776-786.
2.	NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19. 2 million participants. Lancet, 2016, 387(10026): 1377-1396.
3.	國家衛生健康委員會. 中國居民營養與慢性病狀況報告(2020年). 營養學報, 2020, 42(6): 521.
4.	Pan XF, Wang L, Pan A. Epidemiology and determinants of obesity in China. Lancet Diabetes Endocrinol, 2021, 9(6): 373-392.
5.	Wang L, Zhou B, Zhao Z, et al. Body-mass index and obesity in urban and rural China: findings from consecutive nationally representative surveys during 2004-18. Lancet, 2021, 398(10294): 53-63.
6.	中國醫療保健國際交流促進會營養與代謝管理分會, 中國營養學會臨床營養分會, 中華醫學會糖尿病學分會, 等. 中國超重/肥胖醫學營養治療指南(2021). 中國醫學前沿雜志(電子版), 2021, 13(11): 1-55.
7.	Hall KD, Kahan S. Maintenance of lost weight and long-term management of obesity. Med Clin North Am, 2018, 102(1): 183-197.
8.	Field AE, Willett WC, Lissner L, et al. Dietary fat and weight gain among women in the Nurses' Health Study. Obesity, 2007, 15(4): 967-976.
9.	Kossoff EH, Zupec-Kania BA, Auvin S, et al. Optimal clinical management of children receiving dietary therapies for epilepsy: updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open, 2018, 3(2): 175-192.
10.	Chianese R, Coccurello R, Viggiano A, et al. Impact of dietary fats on brain functions. Curr Neuropharmacol, 2018, 16(7): 1059-1085.
11.	Gershuni VM, Yan SL, Medici V. Nutritional ketosis for weight management and reversal of metabolic syndrome. Curr Nutr Rep, 2018, 7(3): 97-106.
12.	Gibson AA, Seimon RV, Lee CM, et al. Do ketogenic diets really suppress appetite: a systematic review and meta-analysis. Obes Rev, 2015, 16(1): 64-76.
13.	Paoli A, Bosco G, Camporesi EM, et al. Ketosis, ketogenic diet and food intake control: a complex relationship. Front Psychol, 2015, 6: 27.
14.	Nagy R. Dr. Atkins' diet revolution:a review. Va Med Mon (1918), 1974, 101(5): 383-385.
15.	Poorshiri B, Barzegar M, Tahmasebi S, et al. The efficacy comparison of classic ketogenic diet and modified Atkins diet in children with refractory epilepsy: a clinical trial. Acta Neurol Belg, 2021, 121(2): 483-487.
16.	Murphy NE, Carrigan CT, Margolis LM. High-fat ketogenic diets and physical performance: a systematic review. Adv Nutr, 2021, 12(1): 223-233.
17.	Bueno NB, de Melo IS, de Oliveira SL, et al. 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.
18.	中華醫學會兒科學分會神經學組, 中國抗癲癇協會, 中華兒科雜志編輯委員會. 生酮飲食療法在癲癇及相關神經系統疾病中的應用專家共識. 中華兒科雜志, 2019, 57(11): 820-825.
19.	中國醫師協會神經內科醫師分會兒童神經專業委員會, 中華醫學會兒科學分會神經學組. 生酮飲食治療兒童癲癇性腦病循證指南. 中華實用兒科臨床雜志, 2019, 34(12): 881-888.
20.	江波, 白文佩, 郁琦, 等. 生酮飲食干預多囊卵巢綜合征中國專家共識(2018年版). 實用臨床醫藥雜志, 2019, 23(1): 1-4.
21.	江波, 鄒大進, 馬向華, 等. 生酮飲食干預2型糖尿病中國專家共識(2019年版). 全科醫學臨床與教育, 2019, 17(4): 291-295.
22.	Trimboli P, Castellana M, Bellido D, et al. Confusion in the nomenclature of ketogenic diets blurs evidence. Rev Endocr Metab Disord, 2020, 21(1): 1-3.
23.	Caprio M, Infante M, Moriconi E, et al. Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE). J Endocrinol Invest, 2019, 42(11): 1365-1386.
24.	Cunha GM, Guzman G, Correa De Mello LL, et al. Efficacy of a 2-month very low-calorie ketogenic diet (VLCKD) compared to a standard low-calorie diet in reducing visceral and liver fat accumulation in patients with obesity. Front Endocrinol (Lausanne), 2020, 11: 607.
25.	Perticone M, Maio R, Sciacqua A, et al. Ketogenic diet-induced weight loss is associated with an increase in vitamin D levels in obese adults. Molecules, 2019, 24(13): 2499.
26.	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.
27.	Merra G, Miranda R, Barrucco S, et al. Very-low-calorie ketogenic diet with aminoacid supplement versus very low restricted-calorie diet for preserving muscle mass during weight loss: a pilot double-blind study. Eur Rev Med Pharmacol Sci, 2016, 20(12): 2613-2621.
28.	Moreno B, Bellido D, Sajoux I, et al. Comparison of a very low-calorie-ketogenic diet with a standard low-calorie diet in the treatment of obesity. Endocrine, 2014, 47(3): 793-805.
29.	Bruci A, Tuccinardi D, Tozzi R, et al. Very Low-calorie ketogenic diet: a safe and effective tool for weight loss in patients with obesity and mild kidney failure. Nutrients, 2020, 12(2): 333.
30.	Moreno B, Crujeiras AB, Bellido D, et al. Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burden of disease. Endocrine, 2016, 54(3): 681-690.
31.	Tragni E, Vigna L, Ruscica M, et al. Reduction of cardio-metabolic risk and body weight through a multiphasic very-low calorie ketogenic diet program in women with overweight/obesity: a study in a real-world setting. Nutrients, 2021, 13(6): 1804.
32.	Michalczyk MM, Klonek G, Maszczyk A, et al. The effects of a low calorie ketogenic diet on glycaemic control variables in hyperinsulinemic overweight/obese females. Nutrients, 2020, 12(6): 1854.
33.	Castellana M, Conte E, Cignarelli A, et al. Efficacy and safety of very low calorie ketogenic diet (VLCKD) in patients with overweight and obesity: a systematic review and meta-analysis. Rev Endocr Metab Disord, 2020, 21(1): 5-16.
34.	Gomez-Arbelaez D, Crujeiras AB, Castro AI, et al. Acid-base safety during the course of a very low-calorie-ketogenic diet. Endocrine, 2017, 58(1): 81-90.
35.	Muscogiuri G, El Ghoch M, Colao A, et al. European guidelines for obesity management in adults with a very low-calorie ketogenic diet: a systematic review and meta-analysis. Obes Facts, 2021, 14(2): 222-245.
36.	Furth SL, Casey JC, Pyzik PL, et al. Risk factors for urolithiasis in children on the ketogenic diet. Pediatr Nephrol, 2000, 15(1-2): 125-128.
37.	Everhart JE. Contributions of obesity and weight loss to gallstone disease. Ann Intern Med, 1993, 119(10): 1029-1035.
38.	蘇綺璇, 侯小兵. 生酮飲食添加療法對藥物難治性癲癇兒童的療效與生活質量的影響. 臨床神經病學雜志, 2021, 34(1): 5-9.
39.	寧澤淑, 楊理明, 廖紅梅, 等. 生酮飲食添加治療兒童難治性癲癇的臨床療效及隨訪研究. 中國醫師雜志, 2018, 20(11): 1676-1679.
40.	陳文杰, 秦炯. 生酮飲食療法治療兒童難治性癲癇作用機制研究進展. 中華實用兒科臨床雜志, 2017, 32(24): 1912-1914.
41.	劉秀, 喬靜敏, 秦英軍, 等. 生酮飲食及限能平衡飲食對超重2型糖尿病患者身體狀況的影響. 中國臨床保健雜志, 2020, 23(6): 823-826.
42.	張營麗, 周艷華, 李卓, 等. 生酮飲食對阿爾茨海默病患者神經損傷及焦慮抑郁情緒的影響. 中國實用神經疾病雜志, 2021, 24(1): 49-53.
43.	周艷茹. 淺析生酮飲食法于體重管理中的應用. 當代體育科技, 2021, 11(16): 35-37.
44.	吳少彬, 岳文婧. 三種不同營養干預方式對肥胖患者減重及代謝的影響分析. 中國實用醫藥, 2020, 15(25): 189-191.

1. Global BMI Mortality Collaboration None, Di Angelantonio E, Bhupathiraju ShN, et al. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet, 2016, 388(10046): 776-786.
2. NCD Risk Factor Collaboration (NCD-RisC). Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19. 2 million participants. Lancet, 2016, 387(10026): 1377-1396.
3. 國家衛生健康委員會. 中國居民營養與慢性病狀況報告(2020年). 營養學報, 2020, 42(6): 521.
4. Pan XF, Wang L, Pan A. Epidemiology and determinants of obesity in China. Lancet Diabetes Endocrinol, 2021, 9(6): 373-392.
5. Wang L, Zhou B, Zhao Z, et al. Body-mass index and obesity in urban and rural China: findings from consecutive nationally representative surveys during 2004-18. Lancet, 2021, 398(10294): 53-63.
6. 中國醫療保健國際交流促進會營養與代謝管理分會, 中國營養學會臨床營養分會, 中華醫學會糖尿病學分會, 等. 中國超重/肥胖醫學營養治療指南(2021). 中國醫學前沿雜志(電子版), 2021, 13(11): 1-55.
7. Hall KD, Kahan S. Maintenance of lost weight and long-term management of obesity. Med Clin North Am, 2018, 102(1): 183-197.
8. Field AE, Willett WC, Lissner L, et al. Dietary fat and weight gain among women in the Nurses' Health Study. Obesity, 2007, 15(4): 967-976.
9. Kossoff EH, Zupec-Kania BA, Auvin S, et al. Optimal clinical management of children receiving dietary therapies for epilepsy: updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open, 2018, 3(2): 175-192.
10. Chianese R, Coccurello R, Viggiano A, et al. Impact of dietary fats on brain functions. Curr Neuropharmacol, 2018, 16(7): 1059-1085.
11. Gershuni VM, Yan SL, Medici V. Nutritional ketosis for weight management and reversal of metabolic syndrome. Curr Nutr Rep, 2018, 7(3): 97-106.
12. Gibson AA, Seimon RV, Lee CM, et al. Do ketogenic diets really suppress appetite: a systematic review and meta-analysis. Obes Rev, 2015, 16(1): 64-76.
13. Paoli A, Bosco G, Camporesi EM, et al. Ketosis, ketogenic diet and food intake control: a complex relationship. Front Psychol, 2015, 6: 27.
14. Nagy R. Dr. Atkins' diet revolution:a review. Va Med Mon (1918), 1974, 101(5): 383-385.
15. Poorshiri B, Barzegar M, Tahmasebi S, et al. The efficacy comparison of classic ketogenic diet and modified Atkins diet in children with refractory epilepsy: a clinical trial. Acta Neurol Belg, 2021, 121(2): 483-487.
16. Murphy NE, Carrigan CT, Margolis LM. High-fat ketogenic diets and physical performance: a systematic review. Adv Nutr, 2021, 12(1): 223-233.
17. Bueno NB, de Melo IS, de Oliveira SL, et al. 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.
18. 中華醫學會兒科學分會神經學組, 中國抗癲癇協會, 中華兒科雜志編輯委員會. 生酮飲食療法在癲癇及相關神經系統疾病中的應用專家共識. 中華兒科雜志, 2019, 57(11): 820-825.
19. 中國醫師協會神經內科醫師分會兒童神經專業委員會, 中華醫學會兒科學分會神經學組. 生酮飲食治療兒童癲癇性腦病循證指南. 中華實用兒科臨床雜志, 2019, 34(12): 881-888.
20. 江波, 白文佩, 郁琦, 等. 生酮飲食干預多囊卵巢綜合征中國專家共識(2018年版). 實用臨床醫藥雜志, 2019, 23(1): 1-4.
21. 江波, 鄒大進, 馬向華, 等. 生酮飲食干預2型糖尿病中國專家共識(2019年版). 全科醫學臨床與教育, 2019, 17(4): 291-295.
22. Trimboli P, Castellana M, Bellido D, et al. Confusion in the nomenclature of ketogenic diets blurs evidence. Rev Endocr Metab Disord, 2020, 21(1): 1-3.
23. Caprio M, Infante M, Moriconi E, et al. Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: systematic review and consensus statement from the Italian Society of Endocrinology (SIE). J Endocrinol Invest, 2019, 42(11): 1365-1386.
24. Cunha GM, Guzman G, Correa De Mello LL, et al. Efficacy of a 2-month very low-calorie ketogenic diet (VLCKD) compared to a standard low-calorie diet in reducing visceral and liver fat accumulation in patients with obesity. Front Endocrinol (Lausanne), 2020, 11: 607.
25. Perticone M, Maio R, Sciacqua A, et al. Ketogenic diet-induced weight loss is associated with an increase in vitamin D levels in obese adults. Molecules, 2019, 24(13): 2499.
26. 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.
27. Merra G, Miranda R, Barrucco S, et al. Very-low-calorie ketogenic diet with aminoacid supplement versus very low restricted-calorie diet for preserving muscle mass during weight loss: a pilot double-blind study. Eur Rev Med Pharmacol Sci, 2016, 20(12): 2613-2621.
28. Moreno B, Bellido D, Sajoux I, et al. Comparison of a very low-calorie-ketogenic diet with a standard low-calorie diet in the treatment of obesity. Endocrine, 2014, 47(3): 793-805.
29. Bruci A, Tuccinardi D, Tozzi R, et al. Very Low-calorie ketogenic diet: a safe and effective tool for weight loss in patients with obesity and mild kidney failure. Nutrients, 2020, 12(2): 333.
30. Moreno B, Crujeiras AB, Bellido D, et al. Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burden of disease. Endocrine, 2016, 54(3): 681-690.
31. Tragni E, Vigna L, Ruscica M, et al. Reduction of cardio-metabolic risk and body weight through a multiphasic very-low calorie ketogenic diet program in women with overweight/obesity: a study in a real-world setting. Nutrients, 2021, 13(6): 1804.
32. Michalczyk MM, Klonek G, Maszczyk A, et al. The effects of a low calorie ketogenic diet on glycaemic control variables in hyperinsulinemic overweight/obese females. Nutrients, 2020, 12(6): 1854.
33. Castellana M, Conte E, Cignarelli A, et al. Efficacy and safety of very low calorie ketogenic diet (VLCKD) in patients with overweight and obesity: a systematic review and meta-analysis. Rev Endocr Metab Disord, 2020, 21(1): 5-16.
34. Gomez-Arbelaez D, Crujeiras AB, Castro AI, et al. Acid-base safety during the course of a very low-calorie-ketogenic diet. Endocrine, 2017, 58(1): 81-90.
35. Muscogiuri G, El Ghoch M, Colao A, et al. European guidelines for obesity management in adults with a very low-calorie ketogenic diet: a systematic review and meta-analysis. Obes Facts, 2021, 14(2): 222-245.
36. Furth SL, Casey JC, Pyzik PL, et al. Risk factors for urolithiasis in children on the ketogenic diet. Pediatr Nephrol, 2000, 15(1-2): 125-128.
37. Everhart JE. Contributions of obesity and weight loss to gallstone disease. Ann Intern Med, 1993, 119(10): 1029-1035.
38. 蘇綺璇, 侯小兵. 生酮飲食添加療法對藥物難治性癲癇兒童的療效與生活質量的影響. 臨床神經病學雜志, 2021, 34(1): 5-9.
39. 寧澤淑, 楊理明, 廖紅梅, 等. 生酮飲食添加治療兒童難治性癲癇的臨床療效及隨訪研究. 中國醫師雜志, 2018, 20(11): 1676-1679.
40. 陳文杰, 秦炯. 生酮飲食療法治療兒童難治性癲癇作用機制研究進展. 中華實用兒科臨床雜志, 2017, 32(24): 1912-1914.
41. 劉秀, 喬靜敏, 秦英軍, 等. 生酮飲食及限能平衡飲食對超重2型糖尿病患者身體狀況的影響. 中國臨床保健雜志, 2020, 23(6): 823-826.
42. 張營麗, 周艷華, 李卓, 等. 生酮飲食對阿爾茨海默病患者神經損傷及焦慮抑郁情緒的影響. 中國實用神經疾病雜志, 2021, 24(1): 49-53.
43. 周艷茹. 淺析生酮飲食法于體重管理中的應用. 當代體育科技, 2021, 11(16): 35-37.
44. 吳少彬, 岳文婧. 三種不同營養干預方式對肥胖患者減重及代謝的影響分析. 中國實用醫藥, 2020, 15(25): 189-191.

Previous Article
Frailty and clinical outcomes in non-cardiovascular surgery heart failure patients: a meta-analysis
Next Article
Efficacy of exercise intervention on smoking cessation: a systematic review

Chinese Journal of Evidence-Based Medicine

Efficacy and safety of a very low-calorie ketogenic diet (VLCKD) in patients with overweight and obesity: a meta-analysis

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content