Effects of ketogenic diets on cardiovascular risk factors: Evidence from animal and human studies

Nutrients

Volumn 9, Issue 5, 2017, Pages

  Kosinski, Christophe ^a   Jornayvaz, François R ^b  

^a LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^b GENEVA UNIVERSITY HOSPITALS   (Switzerland)

Author keywords

Cardiovascular risk factors; Fibroblast growth factor (FGF21); Insulin resistance; Ketogenic diets; NAFLD; Obesity; Type 2 diabetes

Indexed keywords

FIBROBLAST GROWTH FACTOR;

BLOOD PRESSURE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; DYSLIPIDEMIA; FOLLOW UP; HOMEOSTASIS MODEL ASSESSMENT; HUMAN; INSULIN RESISTANCE; KETOGENIC DIET; MEDITERRANEAN DIET; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; REVIEW; WEIGHT REDUCTION; ADMINISTRATION AND DOSAGE; ANIMAL; CARBOHYDRATE DIET; COMPLICATION; DIET THERAPY; PROCEDURES; RISK FACTOR;

ANIMALS; CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; DIET, KETOGENIC; DIETARY CARBOHYDRATES; HUMANS; INSULIN RESISTANCE; NON-ALCOHOLIC FATTY LIVER DISEASE; OBESITY; RISK FACTORS;

EID: 85019577699     PISSN: None     EISSN: 20726643     Source Type: Journal    
DOI: 10.3390/nu9050517     Document Type: Review

References (96)

1. Ng, M.; Fleming, T.; Robinson, M.; Thomson, B.; Graetz, N.; Margono, C.; Mullany, E.C.; Biryukov, S.; Abbafati, C.; Abera, S.F.; et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014, 384, 766-781. [CrossRef]
2. Koh-Banerjee, P.; Wang, Y.; Hu, F.B.; Spiegelman, D.; Willett, W.C.; Rimm, E.B. Changes in body weight and body fat distribution as risk factors for clinical diabetes in US men. Am. J. Epidemiol. 2004, 159, 1150-1159. [CrossRef] [PubMed]
3. Fabbrini, E.; Magkos, F.; Mohammed, B.S.; Pietka, T.; Abumrad, N.A.; Patterson, B.W.; Okunade, A.; Klein, S. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc. Natl. Acad. Sci. USA 2009, 106, 15430-15435. [CrossRef] [PubMed]
4. Fabbrini, E.; Sullivan, S.; Klein, S. Obesity and nonalcoholic fatty liver disease: Biochemical, metabolic, and clinical implications. Hepatology 2010, 51, 679-689. [CrossRef] [PubMed]
5. Chalasani, N.; Younossi, Z.; Lavine, J.E.; Diehl, A.M.; Brunt, E.M.; Cusi, K.; Charlton, M.; Sanyal, A.J. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 2012, 142, 1592-1609. [CrossRef] [PubMed]
6. Gariani, K.; Philippe, J.; Jornayvaz, F.R. Non-alcoholic fatty liver disease and insulin resistance: From bench to bedside. Diabetes Metab. 2013, 39, 16-26. [CrossRef] [PubMed]
7. Machado, M.; Marques-Vidal, P.; Cortez-Pinto, H. Hepatic histology in obese patients undergoing bariatric surgery. J. Hepatol. 2006, 45, 600-606. [CrossRef] [PubMed]
8. McKeown, N.M.; Meigs, J.B.; Liu, S.; Saltzman, E.; Wilson, P.W.F.; Jacques, P.F. Carbohydrate nutrition, insulin resistance, and the prevalence of the metabolic syndrome in the Framingham Offspring Cohort. Diabetes Care 2004, 27, 538-546. [CrossRef] [PubMed]
9. Asrih, M.; Jornayvaz, F.R. Diets and nonalcoholic fatty liver disease: The good and the bad. Clin. Nutr. 2014, 33, 186-190. [CrossRef] [PubMed]
10. Volek, J.S.; Fernandez, M.L.; Feinman, R.D.; Phinney, S.D. Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome. Prog. Lipid Res. 2008, 47, 307-318. [CrossRef] [PubMed]
11. Volek, J.S.; Phinney, S.D.; Forsythe, C.E.; Quann, E.E.;Wood, R.J.; Puglisi, M.J.; Kraemer,W.J.; Bibus, D.M.; Fernandez, M.L.; Feinman, R.D. Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids 2009, 44, 297-309. [CrossRef] [PubMed]
12. Volek, J.S.; Feinman, R.D. Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction. Nutr. Metab. 2005, 2, 31. [CrossRef] [PubMed]
13. Atkins, R.C. Dr Atkins’ Diet Revolution: The High Calorie Way to Stay Thin Forever; D. McKay Co.: New York, NY, USA, 1972.
14. Veech, R.L. The therapeutic implications of ketone bodies: The effects of ketone bodies in pathological conditions: Ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot. Essent. Fat. Acids 2004, 70, 309-319. [CrossRef] [PubMed]
15. Kossoff, E.H.; Cervenka, M.C.; Henry, B.J.; Haney, C.A.; Turner, Z. A decade of the modified Atkins diet (2003-2013): Results, insights, and future directions. Epilepsy Behav. 2013, 29, 437-442. [CrossRef] [PubMed]
16. Feinman, R.D.; Pogozelski, W.K.; Astrup, A.; Bernstein, R.K.; Fine, E.J.; Westman, E.C.; Westman, E.C.; Accurso, A.; Frassetto, L.; Gower, B.A.; et al. Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base. Nutrition 2015, 31, 1-13. [CrossRef] [PubMed]
17. Accurso, A.; Bernstein, R.K.; Dahlqvist, A.; Draznin, B.; Feinman, R.D.; Fine, E.J.; Gleed, A.; Jacobs, D.B.; Larson, G.; Lustig, R.H.; et al. Dietary carbohydrate restriction in type 2 diabetes mellitus and metabolic syndrome: Time for a critical appraisal. Nutr. Metab. 2008, 5, 9. [CrossRef] [PubMed]
18. Owen, O.E.; Morgan, A.P.; Kemp, H.G.; Sullivan, J.M.; Herrera, M.G.; Cahill, G.F. Brain metabolism during fasting. J. Clin. Invest. 1967, 46, 1589-1595. [CrossRef] [PubMed]
19. Kessler, S.K.; Neal, E.G.; Camfield, C.S.; Kossoff, E.H. Dietary therapies for epilepsy: Future research. Epilepsy Behav. 2011, 22, 17-22. [CrossRef] [PubMed]
20. Kennedy, A.R.; Pissios, P.; Otu, H.; Roberson, R.; Xue, B.; Asakura, K.; Furukawa, N.; Marino, F.E.; Liu, F.F.; Kahn, B.B.; et al. A high-fat, ketogenic diet induces a unique metabolic state in mice. Am. J. Physiol. Endocrinol. Metab. 2007, 292, E1724-E1739. [CrossRef] [PubMed]
21. Badman, M.K.; Kennedy, A.R.; Adams, A.C.; Pissios, P.; Maratos-Flier, E. A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss. Am. J. Physiol. Endocrinol. Metab.2009, 297, E1197-E1204. [CrossRef] [PubMed]
22. Garbow, J.R.; Doherty, J.M.; Schugar, R.C.; Travers, S.;Weber, M.L.;Wentz, A.E.; Ezenwajiaku, N.; Cotter, D.G.; Brunt, E.M.; Crawford, P.A. Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet. Am. J. Physiol. Gastrointest. Liver Physiol. 2011, 300, G956-G967. [CrossRef] [PubMed]
23. Bielohuby, M.; Sisley, S.; Sandoval, D.; Herbach, N.; Zengin, A.; Fischereder, M.; Menhofer, D.; Stoehr, B.J.M.; Stemmer, K.; Wanke, R.; et al. Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets. Am. J. Physiol. Endocrinol. Metab. 2013, 305, E1059-E1070. [CrossRef] [PubMed]
24. Jornayvaz, F.R.; Jurczak, M.J.; Lee, H.-Y.; Birkenfeld, A.L.; Frederick, D.W.; Zhang, D.; Zhang, X.M.; Samuel, V.T.; Shulman, G.I. A high-fat, ketogenic diet causes hepatic insulin resistance in mice, despite increasing energy expenditure and preventing weight gain. Am. J. Physiol. Endocrinol. Metab. 2010, 299, E808-E815. [CrossRef] [PubMed]
25. Ellenbroek, J.H.; van Dijck, L.; Tons, H.A.; Rabelink, T.J.; Carlotti, F.; Ballieux, B.E.; de Koning, E.J.P. Long-term ketogenic diet causes glucose intolerance and reduced B- and a-cell mass but no weight loss in mice. Am. J. Physiol. Endocrinol. Metab. 2014, 306, E552-E558. [CrossRef] [PubMed]
26. Douris, N.; Melman, T.; Pecherer, J.M.; Pissios, P.; Flier, J.S.; Cantley, L.C.; Locasale, J.W.; Maratos-Flier, E. Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet. Biochim. Biophys. Acta 2015, 1852, 2056-2065. [CrossRef] [PubMed]
27. Asrih, M.; Altirriba, J.; Rohner-Jeanrenaud, F.; Jornayvaz, F.R. Ketogenic Diet Impairs FGF21 Signaling and Promotes Differential Inflammatory Responses in the Liver and White Adipose Tissue. PLoS ONE 2015, 10, e0126364. [CrossRef] [PubMed]
28. Frommelt, L.; Bielohuby, M.; Menhofer, D.; Stoehr, B.J.M.; Bidlingmaier, M.; Kienzle, E. Effects of low carbohydrate diets on energy and nitrogen balance and body composition in rats depend on dietary protein-to-energy ratio. Nutrition 2014, 30, 863-868. [CrossRef] [PubMed]
29. Holland, A.M.; Kephart, W.C.; Mumford, P.W.; Mobley, C.B.; Lowery, R.P.; Shake, J.J.; Patel, R.K.; Healy, J.C.; McCullough, D.J.; Kluess, H.A.; et al. Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2016, 311, R337-R351. [CrossRef] [PubMed]
30. Partsalaki, I.; Karvela, A.; Spiliotis, B.E. Metabolic impact of a ketogenic diet compared to a hypocaloric diet in obese children and adolescents. J. Pediatr. Endocrinol. Metab. 2012, 25, 697-704. [CrossRef] [PubMed]
31. Saisho, Y.; Butler, A.E.; Manesso, E.; Elashoff, D.; Rizza, R.A.; Butler, P.C. _-cell mass and turnover in humans:Effects of obesity and aging. Diabetes Care 2013, 36, 111-117. [CrossRef] [PubMed]
32. Samaha, F.F.; Iqbal, N.; Seshadri, P.; Chicano, K.L.; Daily, D.A.; McGrory, J.; Williams, T.; Williams, M.; Gracely, E.J.; Stem, L. A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity. N. Engl. J. Med. 2003, 348, 2074-2081. [CrossRef] [PubMed]
33. Foster, G.D.;Wyatt, H.R.; Hill, J.O.; McGuckin, B.G.; Brill, C.; Mohammed, B.S.; Szapary, P.O.; Rader, D.J.; Edman, J.S.; Klein, S. A Randomized Trial of a Low-Carbohydrate Diet for Obesity. N. Engl. J. Med. 2003, 348, 2082-2090. [CrossRef] [PubMed]
34. Westerterp-Plantenga, M.S.; Nieuwenhuizen, A.; Tomé, D.; Soenen, S.; Westerterp, K.R. Dietary protein, weight loss, and weight maintenance. Annu. Rev. Nutr. 2009, 29, 21-41. [CrossRef] [PubMed]
35. Fine, E.J.; Feinman, R.D. Thermodynamics of weight loss diets. Nutr. Metab. 2004, 1, 15. [CrossRef] [PubMed]
36. Feinman, R.D.; Fine, E.J. Nonequilibrium thermodynamics and energy efficiency in weight loss diets. Theor. Biol. Med. Model. 2007, 4, 27. [CrossRef] [PubMed]
37. Halton, T.L.; Hu, F.B. The effects of high protein diets on thermogenesis, satiety and weight loss: A critical review. J. Am. Coll. Nutr. 2004, 23, 373-385. [CrossRef] [PubMed]
38. Veldhorst, M.A.B.;Westerterp-Plantenga, M.S.;Westerterp, K.R. Gluconeogenesis and energy expenditure after a high-protein, carbohydrate-free diet. Am. J. Clin. Nutr. 2009, 90, 519-526. [CrossRef] [PubMed]
39. Sumithran, P.; Prendergast, L.A.; Delbridge, E.; Purcell, K.; Shulkes, A.; Kriketos, A.; Proietto, J. Ketosis and appetite-mediating nutrients and hormones after weight loss. Eur. J. Clin. Nutr. 2013, 67, 759-764. [CrossRef] [PubMed]
40. Johnstone, A.M.; Horgan, G.W.; Murison, S.D.; Bremner, D.M.; Lobley, G.E. Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum. Am. J. Clin. Nutr. 2008, 87, 44-55. [PubMed]
41. Cicero, A.F.G.; Benelli, M.; Brancaleoni, M.; Dainelli, G.; Merlini, D.; Negri, R. Middle and Long-Term Impact of a Very Low-Carbohydrate Ketogenic Diet on Cardiometabolic Factors: A Multi-Center, Cross-Sectional, Clinical Study. High Blood Press. Cardiovasc. Prev. 2015, 22, 389-394. [CrossRef] [PubMed]
42. Paoli, A.; Bianco, A.; Grimaldi, K.A.; Lodi, A.; Bosco, G. Long term successful weight loss with a combination biphasic ketogenic Mediterranean diet and Mediterranean diet maintenance protocol. Nutrients 2013, 5, 5205-5217. [CrossRef] [PubMed]
43. Tay, J.; Luscombe-Marsh, N.D.; Thompson, C.H.; Noakes, M.; Buckley, J.D.; Wittert, G.A.; Yancy, W.S.; Brinkworth, G.D. Comparison of low- and high-carbohydrate diets for type 2 diabetes management:A randomized trial. Am. J. Clin. Nutr. 2015, 102, 780-790. [CrossRef] [PubMed]
44. Jabekk, P.T.; Moe, I.A.; Meen, H.D.; Tomten, S.E.; Høstmark, A.T. Resistance training in overweight women on a ketogenic diet conserved lean body mass while reducing body fat. Nutr. Metab. 2010, 7, 17. [CrossRef] [PubMed]
45. Morris-Stiff, G.; Feldstein, A.E. Fibroblast growth factor 21 as a biomarker for NAFLD: Integrating pathobiology into clinical practice. J. Hepatol. 2010, 53, 795-796. [CrossRef] [PubMed]
46. Dushay, J.; Chui, P.C.; Gopalakrishnan, G.S.; Varela-Rey, M.; Crawley, M.; Fisher, F.M.; Badman, M.K.; Martinez-Chantar, M.L.; Maratos-Flier, E. Increased fibroblast growth factor 21 in obesity and nonalcoholic fatty liver disease. Gastroenterology 2010, 139, 456-463. [CrossRef] [PubMed]
47. Li, H.; Fang, Q.; Gao, F.; Fan, J.; Zhou, J.; Wang, X.; Zhang, H.; Pan, X.; Bao, Y.; Xiang, K.; et al. Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride. J. Hepatol. 2010, 53, 934-940. [CrossRef] [PubMed]
48. Murata, Y.; Nishio, K.; Mochiyama, T.; Konishi, M.; Shimada, M.; Ohta, H.; Itoh, N. Fgf21 Impairs Adipocyte Insulin Sensitivity in Mice Fed a Low-Carbohydrate, High-Fat Ketogenic Diet. PLoS ONE 2013, 8, e69330. [CrossRef] [PubMed]
49. Badman, M.K.; Pissios, P.; Kennedy, A.R.; Koukos, G.; Flier, J.S.; Maratos-Flier, E. Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab. 2007, 5, 426-437. [CrossRef] [PubMed]
50. Jornayvaz, F.R.; Shulman, G.I. Diacylglycerol activation of protein kinase C” and hepatic insulin resistance. Cell Metab. 2012, 15, 574-584. [CrossRef] [PubMed]
51. Camporez, J.P.G.; Jornayvaz, F.R.; Petersen, M.C.; Pesta, D.; Guigni, B.A.; Serr, J.; Zhang, D.; Kahn, M.; Samuel, V.T.; Jurczak, M.J.; et al. Cellular mechanisms by which FGF21 improves insulin sensitivity in male mice. Endocrinology 2013, 154, 3099-3109. [CrossRef] [PubMed]
52. Xu, J.; Lloyd, D.J.; Hale, C.; Stanislaus, S.; Chen, M.; Sivits, G.; Vonderfecht, S.; Hecht, R.; Li, Y.S.; Lindberg, R.A.; et al. Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 2009, 58, 250-259. [CrossRef] [PubMed]
53. Badman, M.K.; Koester, A.; Flier, J.S.; Kharitonenkov, A.; Maratos-Flier, E. Fibroblast growth factor 21-deficient mice demonstrate impaired adaptation to ketosis. Endocrinology 2009, 150, 4931-4940. [CrossRef] [PubMed]
54. Camporez, J.P.G.; Asrih, M.; Zhang, D.; Kahn, M.; Samuel, V.T.; Jurczak, M.J.; Jornayvaz, F.R. Hepatic insulin resistance and increased hepatic glucose production in mice lacking Fgf21. J. Endocrinol. 2015, 226, 207-217. [CrossRef] [PubMed]
55. Laeger, T.; Henagan, T.M.; Albarado, D.C.; Redman, L.M.; Bray, G.A.; Noland, R.C.; Münzberg, H.; Hutson, S.M.; Gettys, T.W.; Schwartz, M.W.; et al. FGF21 is an endocrine signal of protein restriction. J. Clin. Investig. 2014, 124, 3913-3922. [CrossRef] [PubMed]
56. Westerbacka, J.; Lammi, K.; Häkkinen, A.-M.; Rissanen, A.; Salminen, I.; Aro, A.; Yki-Järvinen, H. Dietary fat content modifies liver fat in overweight nondiabetic subjects. J. Clin. Endocrinol. Metab. 2005, 90, 2804-2809. [CrossRef] [PubMed]
57. Kirk, E.; Reeds, D.N.; Finck, B.N.; Mayurranjan, S.M.; Mayurranjan, M.S.; Patterson, B.W.; Klein, S. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology 2009, 136, 1552-1560. [CrossRef] [PubMed]
58. Browning, J.D.; Baker, J.A.; Rogers, T.; Davis, J.; Satapati, S.; Burgess, S.C. Short-term weight loss and hepatic triglyceride reduction: Evidence of a metabolic advantage with dietary carbohydrate restriction. Am. J. Clin. Nutr. 2011, 93, 1048-1052. [CrossRef] [PubMed]
59. Bian, H.; Hakkarainen, A.; Lundbom, N.; Yki-Järvinen, H. Effects of dietary interventions on liver volume in humans. Obesity 2014, 22, 989-995. [CrossRef] [PubMed]
60. Sevastianova, K.; Kotronen, A.; Gastaldelli, A.; Perttilä, J.; Hakkarainen, A.; Lundbom, J.; Orho-Melander, M.; Lundbom, N.; Ferrannini, E.; Rissanen, A.; et al. Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans. Am. J. Clin. Nutr. 2011, 94, 104-111. [CrossRef] [PubMed]
61. Shen, J.; Wong, G.L.-H.; Chan, H.L.-Y.; Chan, R.S.-M.; Chan, H.-Y.; Chu, W.C.-W.; Cheung, B.H.-K.; Yeung, D.K.-W.; Li, L.S.; Sea, M.M.-M.; et al. PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease. J. Gastroenterol. Hepatol. 2015, 30, 139-146. [CrossRef] [PubMed]
62. Jornayvaz, F.R. Fibroblast growth factor 21, ketogenic diets, and insulin resistance. Am. J. Clin. Nutr. 2011, 94, 955. [CrossRef] [PubMed]
63. Kinzig, K.P.; Honors, M.A.; Hargrave, S.L. Insulin sensitivity and glucose tolerance are altered by maintenance on a ketogenic diet. Endocrinology 2010, 151, 3105-3114. [CrossRef] [PubMed]
64. Bisschop, P.H.; de Metz, J.; Ackermans, M.T.; Endert, E.; Pijl, H.; Kuipers, F.; Meijer, A.J.; Sauerwein, H.P.; Romijn, J.A. Dietary fat content alters insulin-mediated glucose metabolism in healthy men. Am. J. Clin. Nutr. 2001, 73, 554-559. [PubMed]
65. Westman, E.C.; Feinman, R.D.; Mavropoulos, J.C.; Vernon, M.C.; Volek, J.S.; Wortman, J.A.; Yancy, W.S.; Phinney, S.D. Low-carbohydrate nutrition and metabolism. Am. J. Clin. Nutr. 2007, 86, 276-284. [PubMed]
66. Hussain, T.A.; Mathew, T.C.; Dashti, A.A.; Asfar, S.; Al-Zaid, N.; Dashti, H.M. Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. Nutrition 2012, 28, 1016-1021. [CrossRef] [PubMed]
67. Gannon, M.C.; Nuttall, F.Q. Control of blood glucose in type 2 diabetes without weight loss by modification of diet composition. Nutr. Metab. 2006, 3, 16. [CrossRef] [PubMed]
68. Boden, G.; Sargrad, K.; Homko, C.; Mozzoli, M.; Stein, T.P. Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes. Ann. Intern. Med. 2005, 142, 403-411. [CrossRef] [PubMed]
69. Mayer, S.B.; Jeffreys, A.S.; Olsen, M.K.; McDuffie, J.R.; Feinglos, M.N.; Yancy, W.S. Two diets with different haemoglobin A1c and antiglycaemic medication effects despite similar weight loss in type 2 diabetes. Diabetes Obes. Metab. 2014, 16, 90-93. [CrossRef] [PubMed]
70. Tay, J.; Luscombe-Marsh, N.D.; Thompson, C.H.; Noakes, M.; Buckley, J.D.; Wittert, G.A.; Yancy, W.S.; Brinkworth, G.D. A Very Low-Carbohydrate, Low-Saturated Fat Diet for Type 2 Diabetes Management: A Randomized Trial. Diabetes Care 2014, 37, 2909-2918. [CrossRef] [PubMed]
71. Gannon, M.C.; Nuttall, F.Q. Effect of a high-protein, low-carbohydrate diet on blood glucose control in people with type 2 diabetes. Diabetes 2004, 53, 2375-2382. [CrossRef] [PubMed]
72. Halton, T.L.; Liu, S.; Manson, J.E.; Hu, F.B. Low-carbohydrate-diet score and risk of type 2 diabetes in women. Am. J. Clin. Nutr. 2008, 87, 339-346. [PubMed]
73. Yancy,W.S.; Foy, M.; Chalecki, A.M.; Vernon, M.C.;Westman, E.C. A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Nutr. Metab. 2005, 2, 34. [CrossRef] [PubMed]
74. Saslow, L.R.; Kim, S.; Daubenmier, J.J.; Moskowitz, J.T.; Phinney, S.D.; Goldman, V.; Murphy, E.J.; Cox, R.M.; Moran, P.; Hecht, F.M. A randomized pilot trial of a moderate carbohydrate diet compared to a very low carbohydrate diet in overweight or obese individuals with type 2 diabetes mellitus or prediabetes. PLoS ONE 2014, 9, e91027. [CrossRef] [PubMed]
75. Dashti, H.M.; Al-Zaid, N.S.; Mathew, T.C.; Al-Mousawi, M.; Talib, H.; Asfar, S.K.; Behbahani, A.I. Long term effects of ketogenic diet in obese subjects with high cholesterol level. Mol. Cell. Biochem. 2006, 286, 1-9. [CrossRef] [PubMed]
76. Iqbal, N.; Vetter, M.L.; Moore, R.H.; Chittams, J.L.; Dalton-Bakes, C.V.; Dowd, M.; Williams-Smith, C.; Cardillo, S.;Wadden, T.A. Effects of a low-intensity intervention that prescribed a low-carbohydrate vs. a low-fat diet in obese, diabetic participants. Obesity 2010, 18, 1733-1738. [CrossRef] [PubMed]
77. De Koning, L.; Fung, T.T.; Liao, X.; Chiuve, S.E.; Rimm, E.B.; Willett, W.C.; Spiegelman, D.; Hu, F.B. Low-carbohydrate diet scores and risk of type 2 diabetes in men. Am. J. Clin. Nutr. 2011, 93, 844-850. [CrossRef] [PubMed]
78. Gumbiner, B.; Wendel, J.A.; McDermott, M.P. Effects of diet composition and ketosis on glycemia during very-low-energy-diet therapy in obese patients with non-insulin-dependent diabetes mellitus. Am. J. Clin. Nutr. 1996, 63, 110-115. [PubMed]
79. Farrés, J.; Pujol, A.; Coma, M.; Ruiz, J.; Naval, J.; Mas, J.; Molins, A.; Fondevila, J.; Aloy, P. Revealing the molecular relationship between type 2 diabetes and the metabolic changes induced by a very-low-carbohydrate low-fat ketogenic diet. Nutr. Metab. 2010, 7, 88. [CrossRef] [PubMed]
80. Sharman, M.J.; Kraemer, W.J.; Love, D.M.; Avery, N.G.; Gómez, A.L.; Scheett, T.P.; Volek, J.S. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. J. Nutr. 2002, 132, 1879-1885. [PubMed]
81. Volek, J.S.; Sharman, M.J.; Forsythe, C.E. Modification of lipoproteins by very low-carbohydrate diets. J. Nutr. 2005, 135, 1339-1342. [PubMed]
82. Foster, G.D.; Wyatt, H.R.; Hill, J.O.; Makris, A.P.; Rosenbaum, D.L.; Brill, C.; Stein, R.I.; Mohammed, B.S.; Miller, B.; Rader, D.J.; et al. Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: A randomized trial. Ann. Intern. Med. 2010, 153, 147-157. [CrossRef] [PubMed]
83. Brinkworth, G.D.; Noakes, M.; Buckley, J.D.; Keogh, J.B.; Clifton, P.M. Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. Am. J. Clin. Nutr. 2009, 90, 23-32. [CrossRef] [PubMed]
84. Lima, P.A.; de Brito Sampaio, L.P.; Damasceno, N.R.T. Ketogenic diet in epileptic children: Impact on lipoproteins and oxidative stress. Nutr. Neurosci. 2015, 18, 337-344. [CrossRef] [PubMed]
85. Westman, E.C.; Yancy,W.S.; Mavropoulos, J.C.; Marquart, M.; McDuffie, J.R. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr. Metab.2008, 5, 36. [CrossRef] [PubMed]
86. Stern, L.; Iqbal, N.; Seshadri, P.; Chicano, K.L.; Daily, D.A.; McGrory, J.;Williams, M.; Gracely, E.J.; Samaha, F.F. The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: One-year follow-up of a randomized trial. Ann. Intern. Med. 2004, 140, 778-785. [CrossRef] [PubMed]
87. De Souza, R.J.; Mente, A.; Maroleanu, A.; Cozma, A.I.; Ha, V.; Kishibe, T.; Uleryk, E.; Budylowski, P.; Schünemann, H.; Beyene, J.; et al. Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: Systematic review and meta-analysis of observational studies. BMJ 2015, 351, h3978. [CrossRef] [PubMed]
88. Fung, T.T.; van Dam, R.M.; Hankinson, S.E.; Stampfer, M.;Willett,W.C.; Hu, F.B. Low-carbohydrate diets and all-cause and cause-specific mortality: Two cohort studies. Ann. Intern. Med. 2010, 153, 289-298. [CrossRef] [PubMed]
89. Ye, F.; Li, X.-J.; Jiang,W.-L.; Sun, H.-B.; Liu, J. Efficacy of and Patient Compliance with a Ketogenic Diet in Adults with Intractable Epilepsy: A Meta-Analysis. J. Clin. Neurol. 2015, 11, 26. [CrossRef] [PubMed]
90. Santos, F.L.; Esteves, S.S.; da Costa Pereira, A.; Yancy, W.S., Jr.; Nunes, J.P. Systematic review and meta-analysis of clinical trials of the effects of low carbohydrate diets on cardiovascular risk factors: Low carbohydrate diets and cardiovascular risk factors. Obes. Rev. 2012, 13, 1048-1066. [CrossRef] [PubMed]
91. Bueno, N.B.; de Melo, I.S.; de Oliveira, S.L.; 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, 1178-1187. [CrossRef] [PubMed]
92. Naude, C.E.; Schoonees, A.; Senekal, M.; Young, T.; Garner, P.; Volmink, J. Low carbohydrate versus isoenergetic balanced diets for reducing weight and cardiovascular risk: A systematic review and meta-analysis. PLoS ONE 2014, 9, e100652. [CrossRef] [PubMed]
93. Bergqvist, A.G.C. Long-term monitoring of the ketogenic diet: Do’s and Don’ts. Epilepsy Res. 2012, 100, 261-266. [CrossRef] [PubMed]
94. Kossoff, E.;Wang, H.-S. Dietary Therapies for Epilepsy. Biomed. J. 2013, 36, 2. [CrossRef] [PubMed]
95. Lagiou, P.; Sandin, S.; Weiderpass, E.; Lagiou, A.; Mucci, L.; Trichopoulos, D.; Adami, H.-O. Low carbohydrate-high protein diet and mortality in a cohort of Swedish women. J. Intern. Med. 2007, 261, 366-374. [CrossRef] [PubMed]
96. Trichopoulou, A.; Psaltopoulou, T.; Orfanos, P.; Hsieh, C.-C.; Trichopoulos, D. Low-carbohydratehigh- protein diet and long-term survival in a general population cohort. Eur. J. Clin. Nutr. 2007, 61, 575-581. [CrossRef] [PubMed]