Effects of medium chain triglycerides supplementation on insulin sensitivity and beta cell function: A feasibility study

Autoři: Dylan D. Thomas aff001;  Mary-Catherine Stockman aff002;  Liqun Yu aff002;  Tova Meshulam aff001;  Ashley C. McCarthy aff001;  Annaliese Ionson aff003;  Nathan Burritt aff002;  Jude Deeney aff001;  Howard Cabral aff004;  Barbara Corkey aff001;  Nawfal Istfan aff001;  Caroline M. Apovian aff001
Působiště autorů: Department of Medicine, Section of Endocrinology, Diabetes, Nutrition and Weight Management, Boston University, MA, United States of America aff001;  Department of Medicine, Section of Endocrinology, Diabetes and Nutrition and Weight Management, Nutrition and Weight Management Center, Boston Medical Center, Boston, MA, United States of America aff002;  Boston University School of Medicine, Boston, MA, United States of America aff003;  Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226200



Medium chain triglycerides (MCT) have unique metabolic properties which may improve insulin sensitivity (Si) and beta cell function but data in humans are limited. We conducted a 6-week clinical trial of MCT oil supplementation.


22 subjects without diabetes (8 males, 14 females, mean ± standard error age 39±2.9 years, baseline BMI 27.0±1.4 kg/m2) were counseled to maintain their body weight and physical activity (PA) during the trial. Dietary intake, PA data, body composition, and resting energy expenditure (REE) were obtained through dietary recall, international PA questionnaire, dual x-ray absorptiometry, and indirect calorimetry, respectively. MCT prescriptions were given based on REE and PA to replace part of dietary fat with 30 grams of MCT per 2000 kcal daily. Insulin-modified frequently sampled intravenous glucose tolerance tests were performed before and after MCT to measure changes in Si, acute insulin response (AIR), disposition index (DI), and glucose effectiveness (Sg).


MCT were well tolerated and weight remained stable (mean change 0.3 kg, p = 0.39). Fasting REE, respiratory quotient, and body composition were stable during the intervention. There were no significant changes in mean fasting glucose, insulin, insulin resistance, fasting total ketones, Si, AIR, DI, Sg, leptin, fructosamine, and proinsulin. The mean change in Si was 0.5 10−4 min-1 per mU/L (95% CI: -1.4, 2.4), corresponding to a 12% increase from baseline, and the range was -4.7 to 12.9 10−4 min-1 per mU/L. Mean total adiponectin decreased significantly from 22925 ng/mL at baseline to 17598 ng/mL at final visit (p = 0.02). The baseline clinical and laboratory parameters were not significantly associated with the change in Si.


There were a wide range of changes in the minimal model parameters of glucose and insulin metabolism in subjects following 6 weeks of MCT as an isocaloric substitution for part of usual dietary fat intake. Since this was a single-arm non-randomized study without a control group, it cannot be certain whether these changes were due to MCT so further randomized controlled trials are warranted.

Klíčová slova:

Adiponectin – Bioenergetics – Diet – Fats – Indirect calorimetry – Insulin – Ketones – Oils


1. Centers for Disease Control and Prevention. National diabetes statistics report, 2017. Atlanta, GA: Centers for Disease Control and Prevention. 2017.

2. Hu FB. Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes care. 2011;34(6):1249–57. doi: 10.2337/dc11-0442 21617109

3. Ferdinand KC, Nasser SA. Racial/ethnic disparities in prevalence and care of patients with type 2 diabetes mellitus. Curr Med Res Opin. 2015;31(5):913–23. doi: 10.1185/03007995.2015.1029894 25772230

4. Nolan CJ, Madiraju MS, Delghingaro-Augusto V, Peyot M-L, Prentki M. Fatty acid signaling in the β-cell and insulin secretion. Diabetes. 2006;55(Supplement 2):S16–S23.

5. Stein DT, Stevenson BE, Chester MW, Basit M, Daniels MB, Turley SD, et al. The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation. The Journal of clinical investigation. 1997;100(2):398–403. doi: 10.1172/JCI119546 9218517

6. Hommelberg PP, Plat J, Langen RC, Schols AM, Mensink RP. Fatty acid-induced NF-κB activation and insulin resistance in skeletal muscle are chain length dependent. American Journal of Physiology-Endocrinology and Metabolism. 2009;296(1):E114–E20. doi: 10.1152/ajpendo.00436.2007 18957619

7. Liberato MV, Nascimento AS, Ayers SD, Lin JZ, Cvoro A, Silveira RL, et al. Medium chain fatty acids are selective peroxisome proliferator activated receptor (PPAR) γ activators and pan-PPAR partial agonists. PLoS One. 2012;7(5):e36297. doi: 10.1371/journal.pone.0036297 22649490

8. de Oliveira Chamma CM, Bargut TCL, Mandarim-de-Lacerda CA, Aguila MB. A rich medium-chain triacylglycerol diet benefits adiposity but has adverse effects on the markers of hepatic lipogenesis and beta-oxidation. Food & function. 2017;8(2):778–87.

9. Montgomery MK, Osborne B, Brown SH, Small L, Mitchell TW, Cooney GJ, et al. Contrasting metabolic effects of medium-vs. long-chain fatty acids in skeletal muscle. Journal of lipid research. 2013:jlr. M040451.

10. Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, et al. Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science. 2013;339(6116):211–4. doi: 10.1126/science.1227166 23223453

11. Youm Y-H, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, et al. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nature medicine. 2015;21(3):263. doi: 10.1038/nm.3804 25686106

12. Stockman M-C, Thomas D, Burke J, Apovian CM. Intermittent Fasting: Is the Wait Worth the Weight? Curr Obes Rep. 2018;7:172–85. doi: 10.1007/s13679-018-0308-9 29700718

13. Ericson U, Hellstrand S, Brunkwall L, Schulz C-A, Sonestedt E, Wallström P, et al. Food sources of fat may clarify the inconsistent role of dietary fat intake for incidence of type 2 diabetes–. The American journal of clinical nutrition. 2015;101(5):1065–80. doi: 10.3945/ajcn.114.103010 25832335

14. Liu Y-H, Wang J, Zhang R-X, Zhang Y-H, Xu Q, Zhang J-Y, et al. A good response to oil with medium-and long-chain fatty acids in body fat and blood lipid profiles of male hypertriglyceridemic subjects. Asia Pacific journal of clinical nutrition. 2009;18(3):351–8. 19786383

15. Montenegro RM Jr, Montenegro APDR, Fernandes M, Moraes R, Gouveia LMFB, Elias J Jr, et al. Triglyceride-induced diabetes mellitus in congenital generalized lipodystrophy. Journal of Pediatric Endocrinology and Metabolism. 2002;15(4):441–8. doi: 10.1515/jpem.2002.15.4.441 12008692

16. Xue C, Liu Y, Wang J, Zheng Z, Zhang Y, Zhang Y, et al. Chinese hypertriglycerideamic subjects of different ages responded differently to consuming oil with medium-and long-chain fatty acids. Bioscience, biotechnology, and biochemistry. 2009;73(8):1711–7. doi: 10.1271/bbb.80827 19661695

17. Binnert C, Pachiaudi C, Beylot M, Hans D, Vandermander J, Chantre P, et al. Influence of human obesity on the metabolic fate of dietary long-and medium-chain triacylglycerols. The American journal of clinical nutrition. 1998;67(4):595–601. doi: 10.1093/ajcn/67.4.595 9537605

18. St-Onge M, Bourque C, Jones P, Ross R, Parsons W. Medium-versus long-chain triglycerides for 27 days increases fat oxidation and energy expenditure without resulting in changes in body composition in overweight women. Int J Obes (Lond). 2003;27(1):95.

19. St-Onge M, Jones P. Greater rise in fat oxidation with medium-chain triglyceride consumption relative to long-chain triglyceride is associated with lower initial body weight and greater loss of subcutaneous adipose tissue. Int J Obes (Lond). 2003;27(12):1565.

20. St‐Onge MP, Ross R, Parsons WD, Jones PJ. Medium‐chain triglycerides increase energy expenditure and decrease adiposity in overweight men. Obesity research. 2003;11(3):395–402. doi: 10.1038/oby.2003.53 12634436

21. White MD, Papamandjaris AA, Jones PJ. Enhanced postprandial energy expenditure with medium-chain fatty acid feeding is attenuated after 14 d in premenopausal women–. The American journal of clinical nutrition. 1999;69(5):883–9. doi: 10.1093/ajcn/69.5.883 10232626

22. Dulloo A, Fathi M, Mensi N, Girardier L. Twenty-four-hour energy expenditure and urinary catecholamines of humans consuming low-to-moderate amounts of medium-chain triglycerides: a dose-response study in a human respiratory chamber. European journal of clinical nutrition. 1996;50(3):152–8. 8654328

23. Hill JO, Peters JC, Yang D, Sharp T, Kaler M, Abumrad NN, et al. Thermogenesis in humans during overfeeding with medium-chain triglycerides. Metabolism-Clinical and Experimental. 1989;38(7):641–8. doi: 10.1016/0026-0495(89)90101-7 2739575

24. St-Onge M-P, Jones PJ. Physiological effects of medium-chain triglycerides: potential agents in the prevention of obesity. The Journal of nutrition. 2002;132(3):329–32. doi: 10.1093/jn/132.3.329 11880549

25. Seaton TB, Welle SL, Warenko MK, Campbell RG. Thermic effect of medium-chain and long-chain triglycerides in man. The American journal of clinical nutrition. 1986;44(5):630–4. doi: 10.1093/ajcn/44.5.630 3532757

26. St-Onge M-P, Bosarge A. Weight-loss diet that includes consumption of medium-chain triacylglycerol oil leads to a greater rate of weight and fat mass loss than does olive oil–. The American journal of clinical nutrition. 2008;87(3):621–6. doi: 10.1093/ajcn/87.3.621 18326600

27. Mumme K, Stonehouse W. Effects of medium-chain triglycerides on weight loss and body composition: a meta-analysis of randomized controlled trials. Journal of the Academy of Nutrition and Dietetics. 2015;115(2):249–63. doi: 10.1016/j.jand.2014.10.022 25636220

28. Yost TJ, Eckel R. Hypocaloric feeding in obese women: metabolic effects of medium-chain triglyceride substitution. The American journal of clinical nutrition. 1989;49(2):326–30. doi: 10.1093/ajcn/49.2.326 2916452

29. Airhart S, Cade WT, Jiang H, Coggan AR, Racette SB, Korenblat K, et al. A diet rich in medium-chain fatty acids improves systolic function and alters the lipidomic profile in patients with type 2 diabetes: a pilot study. The Journal of Clinical Endocrinology & Metabolism. 2016;101(2):504–12.

30. Tsuji H, Kasai M, Takeuchi H, Nakamura M, Okazaki M, Kondo K. Dietary Medium-Chain Triacylglycerols Suppress Accumulation of Body Fat in a Double-Blind, Controlled Trial in Healthy Men and Women. J Nutr. 2001;131(11):2853–9. doi: 10.1093/jn/131.11.2853 11694608

31. Eckel RH, Hanson AS, Chen AY, Berman JN, Yost TJ, Brass EP. Dietary substitution of medium-chain triglycerides improves insulin-mediated glucose metabolism in NIDDM subjects. Diabetes. 1992;41(5):641–7. 1568535

32. Yost TJ, Erskine JM, Gregg TS, Podlecki DL, Brass EP, Eckel RH. Dietary substitution of medium chain triglycerides in subjects with non-insulin-dependent diabetes mellitus in an ambulatory setting: impact on glycemic control and insulin-mediated glucose metabolism. Journal of the American College of Nutrition. 1994;13(6):615–22. doi: 10.1080/07315724.1994.10718457 7706596

33. Mozaffarian D, Wu JH. Flavonoids, dairy foods, and cardiovascular and metabolic health: a review of emerging biologic pathways. Circulation research. 2018;122(2):369–84. doi: 10.1161/CIRCRESAHA.117.309008 29348256

34. St-Onge M-P, Bosarge A, Goree LLT, Darnell B. Medium chain triglyceride oil consumption as part of a weight loss diet does not lead to an adverse metabolic profile when compared to olive oil. Journal of the American College of Nutrition. 2008;27(5):547–52. doi: 10.1080/07315724.2008.10719737 18845704

35. Craig CL, Marshall AL, Sjorstrom M, Bauman AE, Booth ML, Ainsworth BE, et al. International physical activity questionnaire: 12-country reliability and validity. Medicine and science in sports and exercise. 2003;35(8):1381–95. doi: 10.1249/01.MSS.0000078924.61453.FB 12900694

36. Freund G, Weinsier RL. Standardized ketosis in man following medium chain triglyceride ingestion. Metabolism-Clinical and Experimental. 1966;15(11):980–91. doi: 10.1016/0026-0495(66)90046-1 5922367

37. Finegood DT, Hramiak IM, Dupre J. A modified protocol for estimation of insulin sensitivity with the minimal model of glucose kinetics in patients with insulin-dependent diabetes. The Journal of Clinical Endocrinology & Metabolism. 1990;70(6):1538–49.

38. Baker JR, Johnson RN, Scott DJ. Serum fructosamine concentrations in patients with type II (non-insulin-dependent) diabetes mellitus during changes in management. Br Med J (Clin Res Ed). 1984;288(6429):1484–6.

39. Williamson JR, Corkey BE. [65] Assays of intermediates of the citric acid cycle and related compounds by fluorometric enzyme methods. Methods in enzymology. 13: Elsevier; 1969. p. 434–513.

40. Williamson JR, Corkey BE. [23] Assay of citric acid cycle intermediates and related compounds—Update with tissue metabolite levels and Intracellular Distribution. Methods in enzymology. 55: Elsevier; 1979. p. 200–22. doi: 10.1016/0076-6879(79)55025-3 459841

41. Boston RC, Stefanovski D, Moate PJ, Sumner AE, Watanabe RM, Bergman RN. MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes technology & therapeutics. 2003;5(6):1003–15.

42. Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner R. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9. doi: 10.1007/bf00280883 3899825

43. McAuley KA, Williams SM, Mann JI, Goulding A, Chisholm A, Wilson N, et al. Intensive lifestyle changes are necessary to improve insulin sensitivity: a randomized controlled trial. Diabetes care. 2002;25(3):445–52. doi: 10.2337/diacare.25.3.445 11874928

44. Ingelsson E, Sundström J, Ärnlöv J, Zethelius B, Lind L. Insulin resistance and risk of congestive heart failure. Jama. 2005;294(3):334–41. doi: 10.1001/jama.294.3.334 16030278

45. Ärnlöv J, Pencina MJ, Nam B-H, Meigs JB, Fox CS, Levy D, et al. Relations of insulin sensitivity to longitudinal blood pressure tracking: variations with baseline age, body mass index, and blood pressure. Circulation. 2005;112(12):1719–27. doi: 10.1161/CIRCULATIONAHA.105.535039 16157770

46. Han JR, Deng B, Sun J, Chen CG, Corkey BE, Kirkland JL, et al. Effects of dietary medium-chain triglyceride on weight loss and insulin sensitivity in a group of moderately overweight free-living type 2 diabetic Chinese subjects. Metabolism. 2007;56(7):985–91. doi: 10.1016/j.metabol.2007.03.005 17570262

47. Linscheer WG, Blum AL, Platt RR. Transfer of medium chain fatty acids from blood to spinal fluid in patients with cirrhosis. Gastroenterology. 1970;58(4):509–15. 5438002

48. Scalfi L, Coltorti A, Contaldo F. Postprandial thermogenesis in lean and obese subjects after meals supplemented with medium-chain and long-chain triglycerides. The American journal of clinical nutrition. 1991;53(5):1130–3. doi: 10.1093/ajcn/53.5.1130 2021124

49. Yeh Y-Y, Zee P. Relation of Ketosis to Metabolic Changes Induced by Acute Medium-Chain Triglyceride Feeding in Rats. J Nutr. 1976;106(1):58–67. doi: 10.1093/jn/106.1.58 1245892

50. St-Onge M-P, Mayrsohn B, O'Keeffe M, Kissileff HR, Choudhury AR, Laferrère B. Impact of medium and long chain triglycerides consumption on appetite and food intake in overweight men. European journal of clinical nutrition. 2014;68(10):1134. doi: 10.1038/ejcn.2014.145 25074387

51. Turner N, Hariharan K, TidAng J, Frangioudakis G, Beale SM, Wright LE, et al. Enhancement of muscle mitochondrial oxidative capacity and alterations in insulin action are lipid species-dependent: potent tissue-specific effects of medium chain fatty acids. Diabetes. 2009.

52. Bach AC, Ingenbleek Y, Frey A. The usefulness of dietary medium-chain triglycerides in body weight control: fact or fancy? Journal of lipid research. 1996;37(4):708–26. 8732772

53. Tantibhedhyangkul P, Hashim SA, Van Itallie TB. Effects of ingestion of long-chain and medium-chain triglycerides on glucose tolerance in man. Diabetes. 1967;16(11):796–9. doi: 10.2337/diab.16.11.796 6059336

54. Bergen SS, Hashim SA, Van Itallie TB. Hyperketonemia induced in man by medium-chain triglyceride. Diabetes. 1966;15(10):723–5. doi: 10.2337/diab.15.10.723 5924834

55. Ma S, Huang Q, Tominaga T, Liu C, Suzuki K. An 8-week ketogenic diet alternated interleukin-6, ketolytic and lipolytic gene expression, and enhanced exercise capacity in mice. Nutrients. 2018;10(11):1696.

56. Crozier G, Bois-Joyeux B, Chanez M, Girard J, Peret J. Metabolic effects induced by long-term feeding of medium-chain triglycerides in the rat. Metabolism. 1987;36(8):807–14. doi: 10.1016/0026-0495(87)90122-3 3298941

57. Wang ZV, Scherer PE. Adiponectin, the past two decades. Journal of molecular cell biology. 2016;8(2):93–100. doi: 10.1093/jmcb/mjw011 26993047

58. Takeuchi H, Noguchi O, Sekine S, Kobayashi A, Aoyama T. Lower weight gain and higher expression and blood levels of adiponectin in rats fed medium-chain TAG compared with long-chain TAG. Lipids. 2006;41(2):207–12. doi: 10.1007/s11745-006-5089-3 17707987

59. Ooyama K, Wu J, Nosaka N, Aoyama T, Kasai M. Combined intervention of medium-chain triacylglycerol diet and exercise reduces body fat mass and enhances energy expenditure in rats. Journal of nutritional science and vitaminology. 2008;54(2):136–41. doi: 10.3177/jnsv.54.136 18490843

60. Nagasaki H, Kondo T, Fuchigami M, Hashimoto H, Sugimura Y, Ozaki N, et al. Inflammatory changes in adipose tissue enhance expression of Gpr84, a medium‐chain fatty acid receptor: Tnfα enhances Gpr84 expression in adipocytes. FEBS letters. 2012;586(4):368–72. doi: 10.1016/j.febslet.2012.01.001 22245676

61. Wu JH, Cahill LE, Mozaffarian D. Effect of fish oil on circulating adiponectin: a systematic review and meta-analysis of randomized controlled trials. The Journal of Clinical Endocrinology & Metabolism. 2013;98(6):2451–9.

62. Ferguson L, Laing B, Ellett S. Medium Chain Triglyceride Oil, an Intended Placebo with Unexpected Adverse Effects. Ann Clin Lab Res. 2016;4:3.

63. Veprik A, Laufer D, Weiss S, Rubins N, Walker MD. GPR41 modulates insulin secretion and gene expression in pancreatic β-cells and modifies metabolic homeostasis in fed and fasting states. The FASEB Journal. 2016;30(11):3860–9. doi: 10.1096/fj.201500030R 27550964

64. Won Y-J, Lu VB, Puhl HL, Ikeda SR. β-Hydroxybutyrate modulates N-type calcium channels in rat sympathetic neurons by acting as an agonist for the G-protein-coupled receptor FFA3. Journal of Neuroscience. 2013;33(49):19314–25. doi: 10.1523/JNEUROSCI.3102-13.2013 24305827

65. Siener R, Ehrhardt C, Bitterlich N, Metzner C. Effect of a fat spread enriched with medium-chain triacylglycerols and a special fatty acid-micronutrient combination on cardiometabolic risk factors in overweight patients with diabetes. Nutrition & metabolism. 2011;8(1):21.

Článek vyšel v časopise


2019 Číslo 12