Influence of a ketogenic diet, fish-oil, and calorie restriction on plasma metabolites and lipids in C57BL/6J mice

Nutrition & Metabolism

Thomas N Seyfried¹  Nathan Ta¹  Joshua J Meidenbauer¹ 

[1] Biology Department, Boston College, Chestnut Hill, MA 02467, USA

关键词: Ketones;    Glucose;    Calorie restriction;    Omega-3 fatty acids;    Ketogenic diet;   

Others  :  801278
DOI  :  10.1186/1743-7075-11-23

 received in 2014-01-31, accepted in 2014-05-06,  发布年份 2014

【 摘 要 】

Background

Diet therapies including calorie restriction, ketogenic diets, and fish-oil supplementation have been used to improve health and to treat a variety of neurological and non-neurological diseases.

Methods

We investigated the effects of three diets on circulating plasma metabolites (glucose and β-hydroxybutyrate), hormones (insulin and adiponectin), and lipids over a 32-day period in C57BL/6J mice. The diets evaluated included a standard rodent diet (SD), a ketogenic diet (KD), and a standard rodent diet supplemented with fish-oil (FO). Each diet was administered in either unrestricted (UR) or restricted (R) amounts to reduce body weight by 20%.

Results

The KD-UR increased body weight and glucose levels and promoted a hyperlipidemic profile, whereas the FO-UR decreased body weight and glucose levels and promoted a normolipidemic profile, compared to the SD-UR. When administered in restricted amounts, all three diets produced a similar plasma metabolite profile, which included decreased glucose levels and a normolipidemic profile. Linear regression analysis showed that circulating glucose most strongly predicted body weight and triglyceride levels, whereas calorie intake moderately predicted glucose levels and strongly predicted ketone body levels.

Conclusions

These results suggest that biomarkers of health can be improved when diets are consumed in restricted amounts, regardless of macronutrient composition.

【 授权许可】

   
2014 Meidenbauer et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Stafstrom CE, Rho JM: The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol 2012, 3:59.
• [2]Schroeder JE, Richardson JC, Virley DJ: Dietary manipulation and caloric restriction in the development of mouse models relevant to neurological diseases. Biochim Biophys Acta 1802, 2010:840-846.
• [3]Baranano KW, Hartman AL: The ketogenic diet: uses in epilepsy and other neurologic illnesses. Curr Treat Options Neurol 2008, 10:410-419.
• [4]World Health Organization: Diet, Nutrition, and the Prevention of Chronic Diseases: Report of a Joint WHO/FAO Expert Consultation. Geneva: World Health Organization; 2003.
• [5]Kashiwaya Y, Bergman C, Lee JH, Wan R, King MT, Mughal MR, Okun E, Clarke K, Mattson MP, Veech RL: A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease. Neurobiol Aging 2013, 34:1530-1539.
• [6]Hooper L, Abdelhamid A, Moore HJ, Douthwaite W, Skeaff CM, Summerbell CD: Effect of reducing total fat intake on body weight: systematic review and meta-analysis of randomised controlled trials and cohort studies. BMJ 2012, 345:e7666.
• [7]Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I, Golan R, Fraser D, Bolotin A, Vardi H, Tangi-Rozental O, Zuk-Ramot R, Sarusi B, Brickner D, Schwartz Z, Sheiner E, Marko R, Katorza E, Thiery J, Fiedler GM, Blüher M, Stumvoll M, Stampfer MJ: Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med 2008, 359:229-241.
• [8]Schwarzfuchs D, Golan R, Shai I: Four-year follow-up after two-year dietary interventions. N Engl J Med 2012, 367:1373-1374.
• [9]Hooper L, Summerbell CD, Thompson R, Sills D, Roberts FG, Moore HJ, Davey Smith G: Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane Database Syst Rev 2012, 5:CD002137.
• [10]Volek JS, Phinney SD, Forsythe CE, Quann EE, Wood RJ, Puglisi MJ, Kraemer WJ, Bibus DM, Fernandez ML, Feinman RD: Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids 2009, 44:297-309.
• [11]Greene AE, Todorova MT, Seyfried TN: Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies. J Neurochem 2003, 86:529-537.
• [12]Mantis JG, Fritz CL, Marsh J, Heinrichs SC, Seyfried TN: Improvement in motor and exploratory behavior in Rett syndrome mice with restricted ketogenic and standard diets. Epilepsy Behav 2009, 15:133-141.
• [13]Seyfried TN, Sanderson TM, El-Abbadi MM, McGowan R, Mukherjee P: Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Br J Cancer 2003, 89:1375-1382.
• [14]Seyfried TN, Kiebish MA, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P: Metabolic management of brain cancer. Biochim Biophys Acta 1807, 2011:577-594.
• [15]Maurer GD, Brucker DP, Bahr O, Harter PN, Hattingen E, Walenta S, Mueller-Klieser W, Steinbach JP, Rieger J: Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy. BMC Cancer 2011, 11:315. BioMed Central Full Text
• [16]Veech RL: 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 Fatty Acids 2004, 70:309-319.
• [17]Bough KJ, Valiyil R, Han FT, Eagles DA: Seizure resistance is dependent upon age and calorie restriction in rats fed a ketogenic diet. Epilepsy Res 1999, 35:21-28.
• [18]Mantis JG, Centeno NA, Todorova MT, McGowan R, Seyfried TN: Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies. Nutr Metab (Lond) 2004, 1:11. BioMed Central Full Text
• [19]Eagles DA, Boyd SJ, Kotak A, Allan F: Calorie restriction of a high-carbohydrate diet elevates the threshold of PTZ-induced seizures to values equal to those seen with a ketogenic diet. Epilepsy Res 2003, 54:41-52.
• [20]Zhou W, Mukherjee P, Kiebish MA, Markis WT, Mantis JG, Seyfried TN: The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutr Metab (Lond) 2007, 4:5. BioMed Central Full Text
• [21]Zuccoli G, Marcello N, Pisanello A, Servadei F, Vaccaro S, Mukherjee P, Seyfried TN: Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report. Nutr Metab (Lond) 2010, 7:33. BioMed Central Full Text
• [22]Fine EJ, Segal-Isaacson CJ, Feinman RD, Herszkopf S, Romano MC, Tomuta N, Bontempo AF, Negassa A, Sparano JA: Targeting insulin inhibition as a metabolic therapy in advanced cancer: a pilot safety and feasibility dietary trial in 10 patients. Nutrition 2012, 28:1028-1035.
• [23]Joo NS, Lee DJ, Kim KM, Kim BT, Kim CW, Kim KN, Kim SM: Ketonuria after fasting may be related to the metabolic superiority. J Korean Med Sci 2010, 25:1771-1776.
• [24]Westman EC, Yancy WS, Edman JS, Tomlin KF, Perkins CE: Effect of 6-month adherence to a very low carbohydrate diet program. Am J Med 2002, 113:30-36.
• [25]Yancy WS Jr, Olsen MK, Guyton JR, Bakst RP, Westman EC: A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med 2004, 140:769-777.
• [26]Dashti HM, Al-Zaid NS, Mathew TC, Al-Mousawi M, Talib H, Asfar SK, Behbahani AI: Long term effects of ketogenic diet in obese subjects with high cholesterol level. Mol Cell Biochem 2006, 286:1-9.
• [27]Klement RJ, Frobel T, Albers T, Fikenzer S, Prinzhausen J, Kaemmerer U: A pilot case study on the impact of a self-prescribed ketogenic diet on biochemical parameters and running performance in healthy and physically active individuals. Nutr Med 2013, 1:10.
• [28]Kwiterovich PO Jr, Vining EP, Pyzik P, Skolasky R Jr, Freeman JM: Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children. JAMA 2003, 290:912-920.
• [29]Tendler D, Lin S, Yancy WS Jr, Mavropoulos J, Sylvestre P, Rockey DC, Westman EC: The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. Dig Dis Sci 2007, 52:589-593.
• [30]Brehm BJ, Seeley RJ, Daniels SR, D'Alessio DA: A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab 2003, 88:1617-1623.
• [31]Meckling KA, O'Sullivan C, Saari D: Comparison of a low-fat diet to a low-carbohydrate diet on weight loss, body composition, and risk factors for diabetes and cardiovascular disease in free-living, overweight men and women. J Clin Endocrinol Metab 2004, 89:2717-2723.
• [32]Volek JS, Sharman MJ, Gomez AL, Scheett TP, Kraemer WJ: An isoenergetic very low carbohydrate diet improves serum HDL cholesterol and triacylglycerol concentrations, the total cholesterol to HDL cholesterol ratio and postprandial pipemic responses compared with a low fat diet in normal weight, normolipidemic women. J Nutr 2003, 133:2756-2761.
• [33]De Vivo DC: How to use other drugs (steroids) and the ketogenic diet. In Antiepileptic Drug Therapy in Pediatrics. Edited by Morselli PL, Pippenger CE, Penry JK. New York: Raven Press; 1983:283-293.
• [34]Gilbert DL, Pyzik PL, Freeman JM: The ketogenic diet: seizure control correlates better with serum beta-hydroxybutyrate than with urine ketones. J Child Neurol 2000, 15:787-790.
• [35]Kennedy AR, Pissios P, Otu H, Roberson R, Xue B, Asakura K, Furukawa N, Marino FE, Liu FF, Kahn BB, Libermann TA, Maratos-Flier E: A high-fat, ketogenic diet induces a unique metabolic state in mice. Am J Physiol Endocrinol Metab 2007, 292:E1724-E1739.
• [36]Badman MK, Kennedy AR, Adams AC, 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.
• [37]Kaul N, Kreml R, Austria JA, Richard MN, Edel AL, Dibrov E, Hirono S, Zettler ME, Pierce GN: A comparison of fish oil, flaxseed oil and hempseed oil supplementation on selected parameters of cardiovascular health in healthy volunteers. J Am Coll Nutr 2008, 27:51-58.
• [38]Zulyniak MA, Perreault M, Gerling C, Spriet LL, Mutch DM: Fish oil supplementation alters circulating eicosanoid concentrations in young healthy men. Metabolism 2013, 62:1107-1113.
• [39]Woodman RJ, Mori TA, Burke V, Puddey IB, Watts GF, Beilin LJ: Effects of purified eicosapentaenoic and docosahexaenoic acids on glycemic control, blood pressure, and serum lipids in type 2 diabetic patients with treated hypertension. Am J Clin Nutr 2002, 76:1007-1015.
• [40]Mori TA, Burke V, Puddey IB, Watts GF, O'Neal DN, Best JD, Beilin LJ: Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr 2000, 71:1085-1094.
• [41]Mori TA, Bao DQ, Burke V, Puddey IB, Watts GF, Beilin LJ: Dietary fish as a major component of a weight-loss diet: effect on serum lipids, glucose, and insulin metabolism in overweight hypertensive subjects. Am J Clin Nutr 1999, 70:817-825.
• [42]Dagnelie PC, Rietveld T, Swart GR, Stijnen T, van den Berg JW: Effect of dietary fish oil on blood levels of free fatty acids, ketone bodies and triacylglycerol in humans. Lipids 1994, 29:41-45.
• [43]Degirolamo C, Kelley KL, Wilson MD, Rudel LL: Dietary n-3 LCPUFA from fish oil but not alpha-linolenic acid-derived LCPUFA confers atheroprotection in mice. J Lipid Res 2010, 51:1897-1905.
• [44]Murali G, Milne GL, Webb CD, Stewart AB, McMillan RP, Lyle BC, Hulver MW, Saraswathi V: Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR(-/-) mice. J Lipid Res 2012, 53:2186-2197.
• [45]Yang ZH, Miyahara H, Mori T, Doisaki N, Hatanaka A: Beneficial effects of dietary fish-oil-derived monounsaturated fatty acids on metabolic syndrome risk factors and insulin resistance in mice. J Agric Food Chem 2011, 59:7482-7489.
• [46]Mori T, Kondo H, Hase T, Tokimitsu I, Murase T: Dietary fish oil upregulates intestinal lipid metabolism and reduces body weight gain in C57BL/6J mice. J Nutr 2007, 137:2629-2634.
• [47]Wong SH, Nestel PJ, Trimble RP, Storer GB, Illman RJ, Topping DL: The adaptive effects of dietary fish and safflower oil on lipid and lipoprotein metabolism in perfused rat liver. Biochim Biophys Acta 1984, 792:103-109.
• [48]Maalouf M, Rho JM, Mattson MP: The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res Rev 2009, 59:293-315.
• [49]Hursting SD, Smith SM, Lashinger LM, Harvey AE, Perkins SN: Calories and carcinogenesis: lessons learned from 30 years of calorie restriction research. Carcinogenesis 2010, 31:83-89.
• [50]Weiss EP, Fontana L: Caloric restriction: powerful protection for the aging heart and vasculature. Am J Physiol Heart Circ Physiol 2011, 301:H1205-H1219.
• [51]Wu P, Shen Q, Dong S, Xu Z, Tsien JZ, Hu Y: Calorie restriction ameliorates neurodegenerative phenotypes in forebrain-specific presenilin-1 and presenilin-2 double knockout mice. Neurobiol Aging 2008, 29:1502-1511.
• [52]Fontana L, Meyer TE, Klein S, Holloszy JO: Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A 2004, 101:6659-6663.
• [53]Holloszy JO, Fontana L: Caloric restriction in humans. Exp Gerontol 2007, 42:709-712.
• [54]Fontana L, Villareal DT, Weiss EP, Racette SB, Steger-May K, Klein S, Holloszy JO: Calorie restriction or exercise: effects on coronary heart disease risk factors. A randomized, controlled trial. Am J Physiol Endocrinol Metab 2007, 293:E197-E202.
• [55]Johnson JB, Summer W, Cutler RG, Martin B, Hyun DH, Dixit VD, Pearson M, Nassar M, Telljohann R, Maudsley S, Carlson O, John S, Laub DR, Mattson MP: Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med 2007, 42:665-674.
• [56]Knopp RH, Magee MS, Raisys V, Benedetti T, Bonet B: Hypocaloric diets and ketogenesis in the management of obese gestational diabetic women. J Am Coll Nutr 1991, 10:649-667.
• [57]Mahoney LB, Denny CA, Seyfried TN: Caloric restriction in C57BL/6J mice mimics therapeutic fasting in humans. Lipids Health Dis 2006, 5:13. BioMed Central Full Text
• [58]Greene AE, Todorova MT, McGowan R, Seyfried TN: Caloric restriction inhibits seizure susceptibility in epileptic EL mice by reducing blood glucose. Epilepsia 2001, 42:1371-1378.
• [59]Anson RM, Guo Z, de Cabo R, Iyun T, Rios M, Hagepanos A, Ingram DK, Lane MA, Mattson MP: Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci U S A 2003, 100:6216-6220.
• [60]Bough KJ, Rho JM: Anticonvulsant mechanisms of the ketogenic diet. Epilepsia 2007, 48:43-58.
• [61]Cullingford TE: The ketogenic diet; fatty acids, fatty acid-activated receptors and neurological disorders. Prostaglandins Leukot Essent Fatty Acids 2004, 70:253-264.
• [62]McEvoy C, Young IS, Woodside JV: Fish, n-3 polyunsaturated fatty acids, and cardiovascular disease. In Nutritional Health: Strategies for Disease Prevention. Edited by Temple NJ, Wilson T, Jacobs DRJ. New York: Humana Press; 2012. ISBN Third
• [63]Vijay-Kumar M, Vanegas SM, Patel N, Aitken JD, Ziegler TR, Ganji V: Fish oil rich diet in comparison to saturated fat rich diet offered protection against lipopolysaccharide-induced inflammation and insulin resistance in mice. Nutr Metab (Lond) 2011, 8:16. BioMed Central Full Text
• [64]Simopoulos AP: Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 2002, 21:495-505.
• [65]Simopoulos AP: Omega-3 fatty acids and cardiovascular disease: The epidemiological evidence. Environ Health Prev Med 2002, 6:203-209.
• [66]Calder PC: n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 2006, 83:1505S-1519S.
• [67]Williamson DH, Mellanby J, Krebs HA: Enzymic determination of D(-)-beta-hydroxybutyric acid and acetoacetic acid in blood. Biochem J 1962, 82:90-96.
• [68]Baek RC, Martin DR, Cox NR, Seyfried TN: Comparative analysis of brain lipids in mice, cats, and humans with Sandhoff disease. Lipids 2009, 44:197-205.
• [69]Macala LJ, Yu RK, Ando S: Analysis of brain lipids by high performance thin-layer chromatography and densitometry. J Lipid Res 1983, 24:1243-1250.
• [70]Faul F, Erdfelder E, Lang AG, Buchner A: G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 2007, 39:175-191.
• [71]Reed DR, Tordoff MG, Friedman MI: Enhanced acceptance and metabolism of fats by rats fed a high-fat diet. Am J Physiol 1991, 261:R1084-R1088.
• [72]Trout KK, Homko C, Tkacs NC: Methods of measuring insulin sensitivity. Biol Res Nurs 2007, 8:305-318.
• [73]Lansang MC, Williams GH, Carroll JS: Correlation between the glucose clamp technique and the homeostasis model assessment in hypertension. Am J Hypertens 2001, 14:51-53.
• [74]Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y: Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 2002, 8:731-737.
• [75]Lang TA, Secic M: How to report Statistics in Medicine: Annotated Guidelines for Authors, Editors, and Reviewers. Philadelphia: American College of Physicians; 1997.
• [76]Borghjid S, Feinman RD: Response of C57Bl/6 mice to a carbohydrate-free diet. Nutr Metab (Lond) 2012, 9:69. BioMed Central Full Text
• [77]Feinman RD, Fine EJ: “A calorie is a calorie” violates the second law of thermodynamics. Nutr J 2004, 3:9. BioMed Central Full Text
• [78]Jequier E: Pathways to obesity. Int J Obes Relat Metab Disord 2002, 26(Suppl 2):S12-S17.
• [79]MacLean WC, Warwick P, Food and Agriculture Organization of the United Nations: Food energy: Methods of Analysis and Conversion Factors: Report of a Technical Workshop, Rome, 3–6 December 2002. Food and Agriculture Organization of the United Nations: Rome; 2003.
• [80]Carlson LA, Bottiger LE: Ischaemic heart-disease in relation to fasting values of plasma triglycerides and cholesterol: Stockholm prospective study. Lancet 1972, 1:865-868.
• [81]Kannel WB, Castelli WP, Gordon T: Cholesterol in the prediction of atherosclerotic disease. New perspectives based on the Framingham study. Ann Intern Med 1979, 90:85-91.
• [82]Hokanson JE, Austin MA: Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996, 3:213-219.
• [83]Ansar S, Koska J, Reaven PD: Postprandial hyperlipidemia, endothelial dysfunction and cardiovascular risk: focus on incretins. Cardiovasc Diabetol 2011, 10:61. BioMed Central Full Text
• [84]Bielohuby M, Sisley S, Sandoval D, Herbach N, Zengin A, Fischereder M, Menhofer D, Stoehr BJ, Stemmer K, Wanke R, Tschöp MH, Seeley RJ, Bidlingmaier M: Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets. Am J Physiol Endocrinol Metab 2013, 305:E1059-E1070.
• [85]Ellenbroek JH, van Dijck L, Tons HA, Rabelink TJ, Carlotti F, Ballieux BE, de Koning EJ: Long-term ketogenic diet causes glucose intolerance and reduced beta and alpha cell mass but no weight loss in mice. Am J Physiol Endocrinol Metab 2014, 306:E552-E558.
• [86]Beckman JA, Creager MA, Libby P: Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA 2002, 287:2570-2581.
• [87]Kanter JE, Johansson F, LeBoeuf RC, Bornfeldt KE: Do glucose and lipids exert independent effects on atherosclerotic lesion initiation or progression to advanced plaques? Circ Res 2007, 100:769-781.
• [88]Weinman EO, Strisower EH, Chaikoff IL: Conversion of fatty acids to carbohydrate; application of isotopes to this problem and role of the Krebs cycle as a synthetic pathway. Physiol Rev 1957, 37:252-272.
• [89]Kuksis A, Roberts A, Thompson JS, Myher JJ, Geher K: Plasma phosphatidylcholine/free cholesterol ratio as an indicator for atherosclerosis. Arteriosclerosis 1983, 3:389-397.
• [90]Barber MN, Risis S, Yang C, Meikle PJ, Staples M, Febbraio MA, Bruce CR: Plasma lysophosphatidylcholine levels are reduced in obesity and type 2 diabetes. PLoS One 2012, 7:e41456.
• [91]Kunz F, Stummvoll W: Plasma phosphatidylethanolamine–a better indicator in the predictability of atherosclerotic complications? Atherosclerosis 1971, 13:413-425.
• [92]Jiang XC, Paultre F, Pearson TA, Reed RG, Francis CK, Lin M, Berglund L, Tall AR: Plasma sphingomyelin level as a risk factor for coronary artery disease. Arterioscler Thromb Vasc Biol 2000, 20:2614-2618.
• [93]Schlitt A, Blankenberg S, Yan D, von Gizycki H, Buerke M, Werdan K, Bickel C, Lackner KJ, Meyer J, Rupprecht HJ, Jiang XC: Further evaluation of plasma sphingomyelin levels as a risk factor for coronary artery disease. Nutr Metab (Lond) 2006, 3:5. BioMed Central Full Text
• [94]Salt IP: Examining the role of insulin in the regulation of cardiovascular health. Future Cardiol 2013, 9:39-52.
• [95]Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD, Newgard CB, Farese RV Jr, de Cabo R, Ulrich S, Akassoglou K, Verdin E: Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 2013, 339:211-214.
• [96]Gasior M, Rogawski MA, Hartman AL: Neuroprotective and disease-modifying effects of the ketogenic diet. Behav Pharmacol 2006, 17:431-439.
• [97]Rho JM, Sankar R: The ketogenic diet in a pill: is this possible? Epilepsia 2008, 49(Suppl 8):127-133.
• [98]VanItallie TB, Nufert TH: Ketones: metabolism's ugly duckling. Nutr Rev 2003, 61:327-341.
• [99]Drenick EJ, Alvarez LC, Tamasi GC, Brickman AS: Resistance to symptomatic insulin reactions after fasting. J Clin Invest 1972, 51:2757-2762.
• [100]Neschen S, Morino K, Rossbacher JC, Pongratz RL, Cline GW, Sono S, Gillum M, Shulman GI: Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes 2006, 55:924-928.
• [101]Flachs P, Mohamed-Ali V, Horakova O, Rossmeisl M, Hosseinzadeh-Attar MJ, Hensler M, Ruzickova J, Kopecky J: Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetologia 2006, 49:394-397.
• [102]Deckelbaum RJ, Worgall TS, Seo T: n-3 fatty acids and gene expression. Am J Clin Nutr 2006, 83:1520S-1525S.
• [103]Davidson MH: Mechanisms for the hypotriglyceridemic effect of marine omega-3 fatty acids. Am J Cardiol 2006, 98:27i-33i.
• [104]Lombardo YB, Chicco AG: Effects of dietary polyunsaturated n-3 fatty acids on dyslipidemia and insulin resistance in rodents and humans: a review. J Nutr Biochem 2006, 17:1-13.
• [105]Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, Li P, Lu WJ, Watkins SM, Olefsky JM: GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010, 142:687-698.
• [106]Folsom AR, Jacobs DR Jr, Wagenknecht LE, Winkhart SP, Yunis C, Hilner JE, Savage PJ, Smith DE, Flack JM: Increase in fasting insulin and glucose over seven years with increasing weight and inactivity of young adults. The CARDIA Study. Coronary Artery Risk Development in Young Adults. Am J Epidemiol 1996, 144:235-246.
• [107]Qian Y, Lin Y, Zhang T, Bai J, Chen F, Zhang Y, Luo S, Shen H: The characteristics of impaired fasting glucose associated with obesity and dyslipidaemia in a Chinese population. BMC Public Health 2010, 10:139. BioMed Central Full Text
• [108]Shai I, Stampfer MJ: Weight-loss diets–can you keep it off? Am J Clin Nutr 2008, 88:1185-1186.
• [109]Flatt JP: The difference in the storage capacities for carbohydrate and for fat, and its implications in the regulation of body weight. Ann N Y Acad Sci 1987, 499:104-123.
• [110]O'Keefe JH, Bell DS: Postprandial hyperglycemia/hyperlipidemia (postprandial dysmetabolism) is a cardiovascular risk factor. Am J Cardiol 2007, 100:899-904.
• [111]Ford ES: The metabolic syndrome and mortality from cardiovascular disease and all-causes: findings from the National Health and Nutrition Examination Survey II Mortality Study. Atherosclerosis 2004, 173:309-314.