Full-fat Yogurt and Glucose Tolerance

NCT03577119 | Completed

• 1 other identifier: 18-0295
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This study determines if substituting full-fat yogurt (i.e., whole, 3.25% fat) for non-fat yogurt in the diet can reduce the risk of type 2 diabetes and inflammation in association with changes in the composition of the gastrointestinal bacteria prediabetic male and female volunteers. The central hypothesis is that dairy fat impacts whole body glucose handling and insulin sensitivity as well as inflammation both directly, and indirectly via influencing the gut microbiota composition.

Conditions

Pre-Diabetes

Keywords

Prediabetes; Glucose Tolerance; Bioactive fatty acids; Insulin sensitivity; Diet; Milk fat; Lipid metabolism; Inflammation markers; Fecal microbiota composition; Dairy

Outcome Measures

Primary Outcomes (2)

• Changes in insulin sensitivity and β-cell function: MMTT

  Evaluated through mixed meal tolerance test (MMTT) prior to and post experimental diets. Tests will be quantified using the area under the curve (AUC) of the temporal changes in blood glucose, insulin, C-peptide, and incretins (GLP-1 and GIP) using fasting and serial postprandial blood samples. All measurements will be reported as mol/L.

  Baseline, 4 weeks, and 8 weeks

• Changes in insulin sensitivity and β-cell function: OGTT

  Evaluated through oral glucose tolerance test (OGTT) prior to and post experimental diets. Tests will be quantified using the area under the curve (AUC) of the temporal changes in blood glucose, insulin, C-peptide, and incretins (GLP-1 and GIP) using fasting and serial postprandial blood samples. All measurements will be reported as mol/L.

  Baseline, 4 weeks, and 8 weeks

Secondary Outcomes (3)

• Changes in inflammatory markers

  Baseline, 4 weeks, and 8 weeks

• Changes to Colonic microbiota structure: density

  Baseline, 4 weeks, and 8 weeks

• Changes to Colonic microbiota structure: relative abundance

  Baseline, 4 weeks, and 8 weeks

Study Arms (2)

Full-fat yogurt

EXPERIMENTAL

Participants will receive a 21-day controlled diet that includes three daily servings of whole (3.25% fat) yogurt (38% of energy from fat, 44% of energy from carbohydrates, and 18% of energy from protein).

Dietary Supplement: Full-fat yogurt

Non-fat yogurt (Control)

EXPERIMENTAL

Participants will receive a 21-day controlled diet that includes three daily servings of fat-free yogurt (28% of energy from fat, 54% of energy from carbohydrates, and 18% of energy from protein).

Dietary Supplement: Non-fat yogurt

Interventions

Full-fat yogurt DIETARY_SUPPLEMENT

Controlled diet that includes three daily servings of whole (3.25% fat) yogurt.

Full-fat yogurt

Non-fat yogurt DIETARY_SUPPLEMENT

Controlled diet that includes three daily servings of fat-free yogurt.

Non-fat yogurt (Control)

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women and not expecting major lifestyle changes while on study
• Age 45-75
• Overweight and obesity (BMI 20-45 kg/m2)
• Stable body weight for the last 6 months (no more than a +/- 5% change)
• Diagnosis of prediabetes, defined as either impaired fasting glucose (fasting glucose: 100-125 mg/dL), impaired glucose tolerance (blood glucose levels of between: 140-199 mg/dL 2-hr post 75-g oral glucose tolerance test), and/or a hemoglobin A1C (HbA1C) level ranging from 5.7% to 7.0% (if HbA1C above 6.4%, monotherapy of Metformin)
• Women: Post-Menopausal: no menses previous 12 mos.; Follicular Stimulating Hormone (FSH) \> 20 mIU/mL
• Consuming at least 25% of calories from fat (screening will be based an online fat screener:
• http://nutritionquest.com/wellness/free-assessment-tools-for-individuals/fat-intake-screener/
• Normal cognition
• Read and understand English
• Have a telephone
• Willing to follow the study coordinator's/manager's and dietitian's instructions

You may not qualify if:

• Fasting blood glucose ≥126 mg/dL, HbA1C ≥7.0% without monotheraoy of Metformin
• Subject with any chronic disease, inflammatory disease (e.g., asthma, rheumatoid arthritis, Crohn's disease or inflammatory bowel disease) and previous diagnosis of HIV or hepatitis C
• Pregnant or breastfeeding women or women on hormone replacement therapy (for previous 3 months)
• Intolerance to dairy foods (i.e., lactose intolerance or protein allergy), food allergies, or significant food preferences, dietary restrictions (vegetarian, vegan lifestyle), or food aversions that would interfere with diet adherence
• History of a diagnosed eating disorder
• Known/diagnosed gastrointestinal problems (e.g., inflammatory bowel disease, irritable bowel syndrome, etc.)
• Antibiotics use during the past 6 months
• Habitual use of tobacco or controlled substances, and dietary supplements during the study and 1 month prior to the study
• On medically prescribed diets or following a diet (e.g., to lose weight) or use of obesity or weight-loss treatments such as dietary interventions or pharmacotherapy
• Chronic anti-inflammatory medications, or frequent use (\>25% of the time) of over-the-counter medication including laxatives and antacids (subjects with occasional use of allergy or cold medicine, NSAIDS, acetaminophen, or aspirin will be recruited, but these drugs will not be permitted during the study, except for acute administration up to 3 days prior to the outcome variables).
• Waist circumference \>40 inches in men and \>35 inches in women
• Current diagnosis of uncontrolled hypertension (systolic BP: \>160mmHg, diastolic BP: \>95mmHg), (may receive treatment for hypertension as long as 1) on a stable regime for the previous 6 wk, and 2) no anticipated change while on the study)
• Untreated hyperlipidemia \[may receive treatment for hyperlipidemia (statins) as long as 1) on a stable regime for the previous 6 wk, and 2) no anticipated change while on the study)
• Participation on regular basis in competitive sports or habitual aerobic exercise training, which we will arbitrarily define a consisting of \> 3 bouts/wk of aerobic exercise (unable to speak comfortably) for more than 20 min
• Lifestyle or schedule incompatible with the study protocol

Sponsors & Collaborators

• University of Vermont Medical Center: lead
• National Dairy Council: collaborator

Study Sites (1)

Clinical Research Center, University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Related Publications (71)

• Holmberg S, Thelin A. High dairy fat intake related to less central obesity: a male cohort study with 12 years' follow-up. Scand J Prim Health Care. 2013 Jun;31(2):89-94. doi: 10.3109/02813432.2012.757070. Epub 2013 Jan 15.

  PMID: 23320900 BACKGROUND

• Kratz M, Baars T, Guyenet S. The relationship between high-fat dairy consumption and obesity, cardiovascular, and metabolic disease. Eur J Nutr. 2013 Feb;52(1):1-24. doi: 10.1007/s00394-012-0418-1. Epub 2012 Jul 19.

  PMID: 22810464 BACKGROUND

• Scharf RJ, Demmer RT, DeBoer MD. Longitudinal evaluation of milk type consumed and weight status in preschoolers. Arch Dis Child. 2013 May;98(5):335-40. doi: 10.1136/archdischild-2012-302941. Epub 2013 Mar 18.

  PMID: 23508869 BACKGROUND

• Li, S., Field, A., Rimm, E. & Flint, A. Dairy consumption with onset of overweight and obesity among U.S. adolescents. FASEB J 28, 370.7 (2014).

  BACKGROUND

• Kratz M, Marcovina S, Nelson JE, Yeh MM, Kowdley KV, Callahan HS, Song X, Di C, Utzschneider KM. Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not beta-cell function in humans. Am J Clin Nutr. 2014 Jun;99(6):1385-96. doi: 10.3945/ajcn.113.075457. Epub 2014 Apr 16.

  PMID: 24740208 BACKGROUND

• Yakoob MY, Shi P, Willett WC, Rexrode KM, Campos H, Orav EJ, Hu FB, Mozaffarian D. Circulating Biomarkers of Dairy Fat and Risk of Incident Diabetes Mellitus Among Men and Women in the United States in Two Large Prospective Cohorts. Circulation. 2016 Apr 26;133(17):1645-54. doi: 10.1161/CIRCULATIONAHA.115.018410. Epub 2016 Mar 22.

  PMID: 27006479 BACKGROUND

• Ericson U, Hellstrand S, Brunkwall L, Schulz CA, Sonestedt E, Wallstrom P, Gullberg B, Wirfalt E, Orho-Melander M. Food sources of fat may clarify the inconsistent role of dietary fat intake for incidence of type 2 diabetes. Am J Clin Nutr. 2015 May;101(5):1065-80. doi: 10.3945/ajcn.114.103010. Epub 2015 Apr 1.

  PMID: 25832335 BACKGROUND

• Gijsbers L, Ding EL, Malik VS, de Goede J, Geleijnse JM, Soedamah-Muthu SS. Consumption of dairy foods and diabetes incidence: a dose-response meta-analysis of observational studies. Am J Clin Nutr. 2016 Apr;103(4):1111-24. doi: 10.3945/ajcn.115.123216. Epub 2016 Feb 24.

  PMID: 26912494 BACKGROUND

• Jensen RG. The composition of bovine milk lipids: January 1995 to December 2000. J Dairy Sci. 2002 Feb;85(2):295-350. doi: 10.3168/jds.S0022-0302(02)74079-4.

  PMID: 11913692 BACKGROUND

• Roy CC, Kien CL, Bouthillier L, Levy E. Short-chain fatty acids: ready for prime time? Nutr Clin Pract. 2006 Aug;21(4):351-66. doi: 10.1177/0115426506021004351.

  PMID: 16870803 BACKGROUND

• Barber MC, Clegg RA, Travers MT, Vernon RG. Lipid metabolism in the lactating mammary gland. Biochim Biophys Acta. 1997 Aug 16;1347(2-3):101-26. doi: 10.1016/s0005-2760(97)00079-9. No abstract available.

  PMID: 9295156 BACKGROUND

• Keeney, M. K., Katz, I. & Allison, M.J. On the probable origin of some milk fat acids in rumen microbial lipids. J Am Oil Chem Soc 39, 198-201 (1962).

  BACKGROUND

• Jenkins B, West JA, Koulman A. A review of odd-chain fatty acid metabolism and the role of pentadecanoic Acid (c15:0) and heptadecanoic Acid (c17:0) in health and disease. Molecules. 2015 Jan 30;20(2):2425-44. doi: 10.3390/molecules20022425.

  PMID: 25647578 BACKGROUND

• Palmquist DL, Lock AL, Shingfield KJ, Bauman DE. Biosynthesis of conjugated linoleic acid in ruminants and humans. Adv Food Nutr Res. 2005;50:179-217. doi: 10.1016/S1043-4526(05)50006-8. No abstract available.

  PMID: 16263431 BACKGROUND

• Shingfield KJ, Chilliard Y, Toivonen V, Kairenius P, Givens DI. Trans fatty acids and bioactive lipids in ruminant milk. Adv Exp Med Biol. 2008;606:3-65. doi: 10.1007/978-0-387-74087-4_1. No abstract available.

  PMID: 18183924 BACKGROUND

• Bainbridge ML, Cersosimo LM, Wright AD, Kraft J. Content and Composition of Branched-Chain Fatty Acids in Bovine Milk Are Affected by Lactation Stage and Breed of Dairy Cow. PLoS One. 2016 Mar 1;11(3):e0150386. doi: 10.1371/journal.pone.0150386. eCollection 2016.

  PMID: 26930646 BACKGROUND

• Calder PC. Dietary modification of inflammation with lipids. Proc Nutr Soc. 2002 Aug;61(3):345-58. doi: 10.1079/pns2002166.

  PMID: 12296294 BACKGROUND

• Antoniades C, Bakogiannis C, Tousoulis D, Demosthenous M, Marinou K, Stefanadis C. Platelet activation in atherogenesis associated with low-grade inflammation. Inflamm Allergy Drug Targets. 2010 Dec;9(5):334-45. doi: 10.2174/187152810793938035.

  PMID: 20632958 BACKGROUND

• Bohl M, Bjornshave A, Gregersen S, Hermansen K. Whey and Casein Proteins and Medium-Chain Saturated Fatty Acids from Milk Do Not Increase Low-Grade Inflammation in Abdominally Obese Adults. Rev Diabet Stud. 2016 Summer-Fall;13(2-3):148-157. doi: 10.1900/rds.2016.13.148. Epub 2016 Mar 14.

  PMID: 28012280 BACKGROUND

• Calder PC, Ahluwalia N, Brouns F, Buetler T, Clement K, Cunningham K, Esposito K, Jonsson LS, Kolb H, Lansink M, Marcos A, Margioris A, Matusheski N, Nordmann H, O'Brien J, Pugliese G, Rizkalla S, Schalkwijk C, Tuomilehto J, Warnberg J, Watzl B, Winklhofer-Roob BM. Dietary factors and low-grade inflammation in relation to overweight and obesity. Br J Nutr. 2011 Dec;106 Suppl 3:S5-78. doi: 10.1017/S0007114511005460.

  PMID: 22133051 BACKGROUND

• Cani PD, Osto M, Geurts L, Everard A. Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes. 2012 Jul-Aug;3(4):279-88. doi: 10.4161/gmic.19625. Epub 2012 May 14.

  PMID: 22572877 BACKGROUND

• Lalles JP. Dairy products and the French paradox: Could alkaline phosphatases play a role? Med Hypotheses. 2016 Jul;92:7-11. doi: 10.1016/j.mehy.2016.04.033. Epub 2016 Apr 20.

  PMID: 27241245 BACKGROUND

• Misiak B, Leszek J, Kiejna A. Metabolic syndrome, mild cognitive impairment and Alzheimer's disease--the emerging role of systemic low-grade inflammation and adiposity. Brain Res Bull. 2012 Nov 1;89(3-4):144-9. doi: 10.1016/j.brainresbull.2012.08.003. Epub 2012 Aug 18.

  PMID: 22921944 BACKGROUND

• Perry VH. Contribution of systemic inflammation to chronic neurodegeneration. Acta Neuropathol. 2010 Sep;120(3):277-86. doi: 10.1007/s00401-010-0722-x. Epub 2010 Jul 20.

  PMID: 20644946 BACKGROUND

• Vitale G, Salvioli S, Franceschi C. Oxidative stress and the ageing endocrine system. Nat Rev Endocrinol. 2013 Apr;9(4):228-40. doi: 10.1038/nrendo.2013.29. Epub 2013 Feb 26.

  PMID: 23438835 BACKGROUND

• Poynter ME, Daynes RA. Peroxisome proliferator-activated receptor alpha activation modulates cellular redox status, represses nuclear factor-kappaB signaling, and reduces inflammatory cytokine production in aging. J Biol Chem. 1998 Dec 4;273(49):32833-41. doi: 10.1074/jbc.273.49.32833.

  PMID: 9830030 BACKGROUND

• Hammond RA, Levine R. The economic impact of obesity in the United States. Diabetes Metab Syndr Obes. 2010 Aug 30;3:285-95. doi: 10.2147/DMSOTT.S7384.

  PMID: 21437097 BACKGROUND

• Ferdinand, K. C. et al. Health economics of cardiovascular disease: Defining the research agenda. CVD Prev Control 6, 91-100 (2011).

  BACKGROUND

• O'Neill S, O'Driscoll L. Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obes Rev. 2015 Jan;16(1):1-12. doi: 10.1111/obr.12229. Epub 2014 Nov 18.

  PMID: 25407540 BACKGROUND

• Barbaresko J, Koch M, Schulze MB, Nothlings U. Dietary pattern analysis and biomarkers of low-grade inflammation: a systematic literature review. Nutr Rev. 2013 Aug;71(8):511-27. doi: 10.1111/nure.12035. Epub 2013 Jun 13.

  PMID: 23865797 BACKGROUND

• Minihane AM, Vinoy S, Russell WR, Baka A, Roche HM, Tuohy KM, Teeling JL, Blaak EE, Fenech M, Vauzour D, McArdle HJ, Kremer BH, Sterkman L, Vafeiadou K, Benedetti MM, Williams CM, Calder PC. Low-grade inflammation, diet composition and health: current research evidence and its translation. Br J Nutr. 2015 Oct 14;114(7):999-1012. doi: 10.1017/S0007114515002093. Epub 2015 Jul 31.

  PMID: 26228057 BACKGROUND

• Panagiotakos DB, Pitsavos CH, Zampelas AD, Chrysohoou CA, Stefanadis CI. Dairy products consumption is associated with decreased levels of inflammatory markers related to cardiovascular disease in apparently healthy adults: the ATTICA study. J Am Coll Nutr. 2010 Aug;29(4):357-64. doi: 10.1080/07315724.2010.10719852.

  PMID: 21041810 BACKGROUND

• Labonte ME, Couture P, Richard C, Desroches S, Lamarche B. Impact of dairy products on biomarkers of inflammation: a systematic review of randomized controlled nutritional intervention studies in overweight and obese adults. Am J Clin Nutr. 2013 Apr;97(4):706-17. doi: 10.3945/ajcn.112.052217. Epub 2013 Feb 27.

  PMID: 23446894 BACKGROUND

• Bordoni A, Danesi F, Dardevet D, Dupont D, Fernandez AS, Gille D, Nunes Dos Santos C, Pinto P, Re R, Remond D, Shahar DR, Vergeres G. Dairy products and inflammation: A review of the clinical evidence. Crit Rev Food Sci Nutr. 2017 Aug 13;57(12):2497-2525. doi: 10.1080/10408398.2014.967385.

  PMID: 26287637 BACKGROUND

• Calder PC. Fatty acids and inflammation: the cutting edge between food and pharma. Eur J Pharmacol. 2011 Sep;668 Suppl 1:S50-8. doi: 10.1016/j.ejphar.2011.05.085. Epub 2011 Jul 28.

  PMID: 21816146 BACKGROUND

• Kien CL, Bunn JY, Fukagawa NK, Anathy V, Matthews DE, Crain KI, Ebenstein DB, Tarleton EK, Pratley RE, Poynter ME. Lipidomic evidence that lowering the typical dietary palmitate to oleate ratio in humans decreases the leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes. J Nutr Biochem. 2015 Dec;26(12):1599-606. doi: 10.1016/j.jnutbio.2015.07.014. Epub 2015 Aug 1.

  PMID: 26324406 BACKGROUND

• Kien CL, Bunn JY, Poynter ME, Stevens R, Bain J, Ikayeva O, Fukagawa NK, Champagne CM, Crain KI, Koves TR, Muoio DM. A lipidomics analysis of the relationship between dietary fatty acid composition and insulin sensitivity in young adults. Diabetes. 2013 Apr;62(4):1054-63. doi: 10.2337/db12-0363. Epub 2012 Dec 13.

  PMID: 23238293 BACKGROUND

• Kien CL, Matthews DE, Poynter ME, Bunn JY, Fukagawa NK, Crain KI, Ebenstein DB, Tarleton EK, Stevens RD, Koves TR, Muoio DM. Increased palmitate intake: higher acylcarnitine concentrations without impaired progression of beta-oxidation. J Lipid Res. 2015 Sep;56(9):1795-807. doi: 10.1194/jlr.M060137. Epub 2015 Jul 8.

  PMID: 26156077 BACKGROUND

• Vinolo MA, Rodrigues HG, Nachbar RT, Curi R. Regulation of inflammation by short chain fatty acids. Nutrients. 2011 Oct;3(10):858-76. doi: 10.3390/nu3100858. Epub 2011 Oct 14.

  PMID: 22254083 BACKGROUND

• Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. The role of short-chain fatty acids in health and disease. Adv Immunol. 2014;121:91-119. doi: 10.1016/B978-0-12-800100-4.00003-9.

  PMID: 24388214 BACKGROUND

• Andoh A, Fujiyama Y, Hata K, Araki Y, Takaya H, Shimada M, Bamba T. Counter-regulatory effect of sodium butyrate on tumour necrosis factor-alpha (TNF-alpha)-induced complement C3 and factor B biosynthesis in human intestinal epithelial cells. Clin Exp Immunol. 1999 Oct;118(1):23-9. doi: 10.1046/j.1365-2249.1999.01038.x.

  PMID: 10540155 BACKGROUND

• Sales-Campos H, Souza PR, Peghini BC, da Silva JS, Cardoso CR. An overview of the modulatory effects of oleic acid in health and disease. Mini Rev Med Chem. 2013 Feb;13(2):201-10.

  PMID: 23278117 BACKGROUND

• Vassiliou EK, Gonzalez A, Garcia C, Tadros JH, Chakraborty G, Toney JH. Oleic acid and peanut oil high in oleic acid reverse the inhibitory effect of insulin production of the inflammatory cytokine TNF-alpha both in vitro and in vivo systems. Lipids Health Dis. 2009 Jun 26;8:25. doi: 10.1186/1476-511X-8-25.

  PMID: 19558671 BACKGROUND

• Carrillo C, Cavia Mdel M, Alonso-Torre S. Role of oleic acid in immune system; mechanism of action; a review. Nutr Hosp. 2012 Jul-Aug;27(4):978-90. doi: 10.3305/nh.2012.27.4.5783.

  PMID: 23165533 BACKGROUND

• Jacome-Sosa M, Vacca C, Mangat R, Diane A, Nelson RC, Reaney MJ, Shen J, Curtis JM, Vine DF, Field CJ, Igarashi M, Piomelli D, Banni S, Proctor SD. Vaccenic acid suppresses intestinal inflammation by increasing anandamide and related N-acylethanolamines in the JCR:LA-cp rat. J Lipid Res. 2016 Apr;57(4):638-49. doi: 10.1194/jlr.M066308. Epub 2016 Feb 17.

  PMID: 26891736 BACKGROUND

• Jaudszus A, Jahreis G, Schlormann W, Fischer J, Kramer R, Degen C, Rohrer C, Roth A, Gabriel H, Barz D, Gruen M. Vaccenic acid-mediated reduction in cytokine production is independent of c9,t11-CLA in human peripheral blood mononuclear cells. Biochim Biophys Acta. 2012 Oct;1821(10):1316-22. doi: 10.1016/j.bbalip.2012.06.010. Epub 2012 Jun 30.

  PMID: 22750019 BACKGROUND

• Huebner SM, Olson JM, Campbell JP, Bishop JW, Crump PM, Cook ME. Low Dietary c9t11-Conjugated Linoleic Acid Intake from Dairy Fat or Supplements Reduces Inflammation in Collagen-Induced Arthritis. Lipids. 2016 Jul;51(7):807-19. doi: 10.1007/s11745-016-4163-8. Epub 2016 Jun 7.

  PMID: 27270404 BACKGROUND

• Penedo LA, Nunes JC, Gama MA, Leite PE, Quirico-Santos TF, Torres AG. Intake of butter naturally enriched with cis9,trans11 conjugated linoleic acid reduces systemic inflammatory mediators in healthy young adults. J Nutr Biochem. 2013 Dec;24(12):2144-51. doi: 10.1016/j.jnutbio.2013.08.006.

  PMID: 24231103 BACKGROUND

• Reynolds CM, Roche HM. Conjugated linoleic acid and inflammatory cell signalling. Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):199-204. doi: 10.1016/j.plefa.2010.02.021. Epub 2010 Mar 7.

  PMID: 20207526 BACKGROUND

• Stachowska E, Siennicka A, Baskiewcz-Halasa M, Bober J, Machalinski B, Chlubek D. Conjugated linoleic acid isomers may diminish human macrophages adhesion to endothelial surface. Int J Food Sci Nutr. 2012 Feb;63(1):30-5. doi: 10.3109/09637486.2011.593505. Epub 2011 Jul 1.

  PMID: 21721848 BACKGROUND

• Viladomiu M, Hontecillas R, Bassaganya-Riera J. Modulation of inflammation and immunity by dietary conjugated linoleic acid. Eur J Pharmacol. 2016 Aug 15;785:87-95. doi: 10.1016/j.ejphar.2015.03.095. Epub 2015 May 15.

  PMID: 25987426 BACKGROUND

• Poudel-Tandukar K, Nanri A, Matsushita Y, Sasaki S, Ohta M, Sato M, Mizoue T. Dietary intakes of alpha-linolenic and linoleic acids are inversely associated with serum C-reactive protein levels among Japanese men. Nutr Res. 2009 Jun;29(6):363-70. doi: 10.1016/j.nutres.2009.05.012.

  PMID: 19628101 BACKGROUND

• Reifen R, Karlinsky A, Stark AH, Berkovich Z, Nyska A. alpha-Linolenic acid (ALA) is an anti-inflammatory agent in inflammatory bowel disease. J Nutr Biochem. 2015 Dec;26(12):1632-40. doi: 10.1016/j.jnutbio.2015.08.006. Epub 2015 Aug 14.

  PMID: 26350254 BACKGROUND

• Ren J, Chung SH. Anti-inflammatory effect of alpha-linolenic acid and its mode of action through the inhibition of nitric oxide production and inducible nitric oxide synthase gene expression via NF-kappaB and mitogen-activated protein kinase pathways. J Agric Food Chem. 2007 Jun 27;55(13):5073-80. doi: 10.1021/jf0702693. Epub 2007 Jun 2.

  PMID: 17542608 BACKGROUND

• Zhao G, Etherton TD, Martin KR, Gillies PJ, West SG, Kris-Etherton PM. Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. Am J Clin Nutr. 2007 Feb;85(2):385-91. doi: 10.1093/ajcn/85.2.385.

  PMID: 17284733 BACKGROUND

• Mika A, Stepnowski P, Kaska L, Proczko M, Wisniewski P, Sledzinski M, Sledzinski T. A comprehensive study of serum odd- and branched-chain fatty acids in patients with excess weight. Obesity (Silver Spring). 2016 Aug;24(8):1669-76. doi: 10.1002/oby.21560. Epub 2016 Jun 29.

  PMID: 27355152 BACKGROUND

• Rodriguez JM, Murphy K, Stanton C, Ross RP, Kober OI, Juge N, Avershina E, Rudi K, Narbad A, Jenmalm MC, Marchesi JR, Collado MC. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis. 2015 Feb 2;26:26050. doi: 10.3402/mehd.v26.26050. eCollection 2015.

  PMID: 25651996 BACKGROUND

• Salminen S, Gibson GR, McCartney AL, Isolauri E. Influence of mode of delivery on gut microbiota composition in seven year old children. Gut. 2004 Sep;53(9):1388-9. doi: 10.1136/gut.2004.041640. No abstract available.

  PMID: 15306608 BACKGROUND

• Moreno-Indias I, Cardona F, Tinahones FJ, Queipo-Ortuno MI. Impact of the gut microbiota on the development of obesity and type 2 diabetes mellitus. Front Microbiol. 2014 Apr 29;5:190. doi: 10.3389/fmicb.2014.00190. eCollection 2014.

  PMID: 24808896 BACKGROUND

• Mai V, Draganov PV. Recent advances and remaining gaps in our knowledge of associations between gut microbiota and human health. World J Gastroenterol. 2009 Jan 7;15(1):81-5. doi: 10.3748/wjg.15.81.

  PMID: 19115471 BACKGROUND

• Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012 Sep 13;489(7415):220-30. doi: 10.1038/nature11550.

  PMID: 22972295 BACKGROUND

• Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012 Jun 13;486(7402):207-14. doi: 10.1038/nature11234.

  PMID: 22699609 BACKGROUND

• Festi D, Schiumerini R, Eusebi LH, Marasco G, Taddia M, Colecchia A. Gut microbiota and metabolic syndrome. World J Gastroenterol. 2014 Nov 21;20(43):16079-94. doi: 10.3748/wjg.v20.i43.16079.

  PMID: 25473159 BACKGROUND

• Graf D, Di Cagno R, Fak F, Flint HJ, Nyman M, Saarela M, Watzl B. Contribution of diet to the composition of the human gut microbiota. Microb Ecol Health Dis. 2015 Feb 4;26:26164. doi: 10.3402/mehd.v26.26164. eCollection 2015.

  PMID: 25656825 BACKGROUND

• Zimmer J, Lange B, Frick JS, Sauer H, Zimmermann K, Schwiertz A, Rusch K, Klosterhalfen S, Enck P. A vegan or vegetarian diet substantially alters the human colonic faecal microbiota. Eur J Clin Nutr. 2012 Jan;66(1):53-60. doi: 10.1038/ejcn.2011.141. Epub 2011 Aug 3.

  PMID: 21811294 BACKGROUND

• David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014 Jan 23;505(7484):559-63. doi: 10.1038/nature12820. Epub 2013 Dec 11.

  PMID: 24336217 BACKGROUND

• Caesar R, Tremaroli V, Kovatcheva-Datchary P, Cani PD, Backhed F. Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling. Cell Metab. 2015 Oct 6;22(4):658-68. doi: 10.1016/j.cmet.2015.07.026. Epub 2015 Aug 27.

  PMID: 26321659 BACKGROUND

• Caesar R, Nygren H, Oresic M, Backhed F. Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism. J Lipid Res. 2016 Mar;57(3):474-81. doi: 10.1194/jlr.M065847. Epub 2016 Jan 18.

  PMID: 26783361 BACKGROUND

• Walsh, H. H., H.; Cersosimo, L.; Kien, C.L.; Kraft, J. Decreased abundance of firmicutes in the gut microbiota after consumption of a diet containing milk fats. FASEB J 30, 683.611 (2016).

  BACKGROUND

• Taormina VM, Eisenhardt S, Gilbert MP, Poynter ME, Kien CL, Kraft J. Full-fat yogurt compared with non-fat yogurt reduces blood triacylglycerol concentrations and lowers the triacylglycerol content in specific lipoprotein subclasses in adults with prediabetes: an exploratory analysis of a randomized-controlled trial. Lipids Health Dis. 2025 Jun 5;24(1):201. doi: 10.1186/s12944-025-02616-4.

  PMID: 40474187 DERIVED

• Taormina VM, Eisenhardt S, Gilbert MP, Poynter ME, Kien CL, Kraft J. Full-fat versus non-fat yogurt consumption improves glucose homeostasis and metabolic hormone regulation in individuals with prediabetes: A randomized-controlled trial. Nutr Res. 2025 Apr;136:39-52. doi: 10.1016/j.nutres.2025.02.005. Epub 2025 Feb 28.

  PMID: 40139076 DERIVED

MeSH Terms

Conditions

Glucose Intolerance; Prediabetic State; Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Hyperinsulinism

Study Officials

• Jana Kraft, PhD

  University of Vermont

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This study will employ a controlled, randomized, double-blinded crossover trial comparing two diets.

Study Record Dates

• First Submitted: June 1, 2018
• First Posted: July 5, 2018
• Study Start: June 1, 2018
• Primary Completion: April 30, 2022
• Study Completion: June 30, 2022
• Last Updated: June 30, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)