Adverse Metabolic Effects of Dietary Sugar

NCT02548767 | Completed

• 2 other identifiers: 4991061R01HL121324
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

It is not known whether consumption of excessive amounts of sugar can increase risk factors for cardiovascular disease or diabetes in the absence of increased food (caloric) intake and weight gain, nor whether the negative effects of sugar consumption are made worse when accompanied by weight gain. This study will investigate the effects of excess sugar when consumed with an energy-balanced diet that prevents weight gain, and the effects of excess sugar when consumed with a diet that can cause weight gain. The results will determine whether excess sugar consumption and excess caloric intake that lead to weight gain have independent and additive effects on risk factors for cardiovascular disease or diabetes, and will have the potential to influence dietary guidelines and public health policy.

Conditions

Chronic Disease of Cardiovascular System; Type 2 Diabetes; Obesity

Keywords

High fructose corn syrup; Sugar

Outcome Measures

Primary Outcomes (1)

• Change of de novo lipogenesis: palmitate tracer-to-tracee ratios by gas chromatography-mass spectrometry.

  Blood samples are collected during 26-h isotopic acetate infusion. Blood samples are processed for determination of palmitate tracer-to-tracee ratios by gas chromatography-mass spectrometry.

  22 hours at Baseline and 4-week Intervention

Secondary Outcomes (5)

• Change of endogenous glucose production measured by standard dilution techniques

  7 hours at Baseline and 4-week Intervention

• Change of whole body insulin sensitivity

  3 hours at Baseline and 4-week Intervention

• Change of liver lipid

  Baseline, 4-week Intervention and 8-week intervention

• Change of fat oxidation

  17 hours at Baseline and 4-week Intervention

• Change of Very low density lipoprotein (VLDL)-triglyceride (TG) kinetics

  22 hours at Baseline and 4-week Intervention

Other Outcomes (6)

• Change of blood levels of LDL-cholesterol

  Baseline and 4-week Intervention

• Change of blood levels of non-HDL-cholesterol

  Baseline and 4-week Intervention

• Change of blood levels of apolipoprotein B

  Baseline and 4-week Intervention

Study Arms (4)

HFCS-EB

EXPERIMENTAL

Consume 3 servings/day of high fructose corn syrup (HFCS)-sweetened beverage along with the provided energy-balanced diet. The 3 HFCS-sweetened beverages will contain 25% of energy requirement and the remainder of the provided diet will contain 75% of energy requirement. All and only the provided beverage and diet will be consumed for eight weeks.

Other: high fructose corn syrup; Other: Energy-balanced diet

Asp-EB

PLACEBO COMPARATOR

Consume 3 servings/day of aspartame-sweetened beverage along with the provided energy-balanced diet. The 3 aspartame-sweetened beverages will contain 0% of energy requirement and the remainder of the provided diet will contain 100% of energy requirement. All and only the provided beverage and diet will be consumed for eight weeks.

Other: aspartame; Other: Energy-balanced diet

HFCS-AL

EXPERIMENTAL

Consume 3 servings/day of high fructose corn syrup (HFCS)-sweetened beverage along with the provided ad libitum diet. The 3 HFCS-sweetened beverages will contain 25% of energy requirement and the remainder of the provided diet will contain approximately 125% of energy requirement. All the provided beverage will be consumed for eight weeks. Only the provided beverage and diet will be consumed for eight weeks. The provided diet will be consumed ad libitum and the uneaten portions will be returned to study staff.

Other: high fructose corn syrup; Other: Ad libitum diet

Asp-AL

PLACEBO COMPARATOR

Consume 3 servings/day of aspartame-sweetened beverage along with the provided ad libitum diet. The 3 aspartame-sweetened beverages will contain 0% of energy requirement and the remainder of the provided diet will contain approximately 125% of energy requirement. All the provided beverage will be consumed for eight weeks. Only the provided beverage and diet will be consumed for eight weeks. The provided diet will be consumed ad libitum and the uneaten portions will be returned to study staff.

Other: aspartame; Other: Ad libitum diet

Interventions

high fructose corn syrup OTHER

High fructose corn syrup provided as 15% HFCS/85% water (weight/weight) fruit-flavored beverage

Also known as: sugar, HFCS, high fructose corn syrup-55, HFCS-55

HFCS-AL; HFCS-EB

aspartame OTHER

Aspartame provided as 0.04% aspartame/99.96% water (weight/weight), fruit-flavored beverage

Also known as: non-caloric sweetener

Asp-AL; Asp-EB

Energy-balanced diet OTHER

Provided in quantities that equal energy requirement. Formulated such that the overall macronutrient intake; including beverage; equal 45%/5% energy requirement at complex/simple carbohydrate, 35% energy requirement as fat, 15% energy requirement as protein.

Also known as: Weight-maintaining diet

Asp-EB; HFCS-EB

Ad libitum diet OTHER

Provided in quantities that exceed energy requirement by approximately 25%. Formulated such that the overall macronutrient intake; including beverage; equals approximately 45%/5% energy requirement at complex/simple carbohydrate, 35% energy requirement as fat, 15% energy requirement as protein.

Also known as: Positive-energy diet

Asp-AL; HFCS-AL

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI 22-28 kg/m2
• Self-reported stable body weight during the prior six months

You may not qualify if:

• Fasting glucose \>105 mg/dl
• Evidence of liver disorder \[AST (Aspartate Aminotransferase) or ALT (Alanine Aminotransferase)\] \>200% upper limit of normal range)
• Evidence of kidney disorder (\>2.0mg/dl creatinine)
• Evidence of thyroid disorder (out of normal range)
• Systolic blood pressure consistently over 140mm Hg (mercury) or diastolic blood pressure over 90mmHg
• Triglycerides \> 200mg/dl
• LDL-C \> 130mg/dl in combination with Chol:HDL \> 4
• Hemoglobin \< 8.5 g/dL
• Pregnant or lactating women
• Any other condition that, in the opinion of the investigators, would put the subject at risk
• Current, prior (within 12 months), or anticipated use of any hypolipidemic or anti-diabetic agents.
• Use of thyroid, anti-hypertensive, anti-depressant, weight loss medications or any other medication which, in the opinion of the investigator, may confound study results
• Use of tobacco
• Strenuous exerciser (\>3.5 hours/week at a level more vigorous than walking)
• Surgery for weight loss

Sponsors & Collaborators

• University of California, Davis: lead
• Touro University, California: collaborator
• University of Southern California: collaborator
• USDA, Western Human Nutrition Research Center: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (3)

University of California, Davis

Davis, California, 95616, United States

Location

Clinical Research Center

Sacramento, California, 95655, United States

Location

Touro University California Translational Research Clinic and Student Health Clinic

Vallejo, California, 94592, United States

Location

Related Publications (10)

• Stanhope KL, Schwarz JM, Havel PJ. Adverse metabolic effects of dietary fructose: results from the recent epidemiological, clinical, and mechanistic studies. Curr Opin Lipidol. 2013 Jun;24(3):198-206. doi: 10.1097/MOL.0b013e3283613bca.

  PMID: 23594708 BACKGROUND

• Cox CL, Stanhope KL, Schwarz JM, Graham JL, Hatcher B, Griffen SC, Bremer AA, Berglund L, McGahan JP, Keim NL, Havel PJ. Consumption of fructose- but not glucose-sweetened beverages for 10 weeks increases circulating concentrations of uric acid, retinol binding protein-4, and gamma-glutamyl transferase activity in overweight/obese humans. Nutr Metab (Lond). 2012 Jul 24;9(1):68. doi: 10.1186/1743-7075-9-68.

  PMID: 22828276 BACKGROUND

• Cox CL, Stanhope KL, Schwarz JM, Graham JL, Hatcher B, Griffen SC, Bremer AA, Berglund L, McGahan JP, Havel PJ, Keim NL. Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women. Eur J Clin Nutr. 2012 Feb;66(2):201-8. doi: 10.1038/ejcn.2011.159. Epub 2011 Sep 28.

  PMID: 21952692 BACKGROUND

• Stanhope KL, Bremer AA, Medici V, Nakajima K, Ito Y, Nakano T, Chen G, Fong TH, Lee V, Menorca RI, Keim NL, Havel PJ. Consumption of fructose and high fructose corn syrup increase postprandial triglycerides, LDL-cholesterol, and apolipoprotein-B in young men and women. J Clin Endocrinol Metab. 2011 Oct;96(10):E1596-605. doi: 10.1210/jc.2011-1251. Epub 2011 Aug 17.

  PMID: 21849529 BACKGROUND

• Stanhope KL. Role of fructose-containing sugars in the epidemics of obesity and metabolic syndrome. Annu Rev Med. 2012;63:329-43. doi: 10.1146/annurev-med-042010-113026. Epub 2011 Oct 27.

  PMID: 22034869 BACKGROUND

• Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer AA, Graham JL, Hatcher B, Cox CL, Dyachenko A, Zhang W, McGahan JP, Seibert A, Krauss RM, Chiu S, Schaefer EJ, Ai M, Otokozawa S, Nakajima K, Nakano T, Beysen C, Hellerstein MK, Berglund L, Havel PJ. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J Clin Invest. 2009 May;119(5):1322-34. doi: 10.1172/JCI37385. Epub 2009 Apr 20.

  PMID: 19381015 BACKGROUND

• Maersk M, Belza A, Stodkilde-Jorgensen H, Ringgaard S, Chabanova E, Thomsen H, Pedersen SB, Astrup A, Richelsen B. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr. 2012 Feb;95(2):283-9. doi: 10.3945/ajcn.111.022533. Epub 2011 Dec 28.

  PMID: 22205311 BACKGROUND

• Aeberli I, Hochuli M, Gerber PA, Sze L, Murer SB, Tappy L, Spinas GA, Berneis K. Moderate amounts of fructose consumption impair insulin sensitivity in healthy young men: a randomized controlled trial. Diabetes Care. 2013 Jan;36(1):150-6. doi: 10.2337/dc12-0540. Epub 2012 Aug 28.

  PMID: 22933433 BACKGROUND

• Schwarz JM, Noworolski SM, Wen MJ, Dyachenko A, Prior JL, Weinberg ME, Herraiz LA, Tai VW, Bergeron N, Bersot TP, Rao MN, Schambelan M, Mulligan K. Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat. J Clin Endocrinol Metab. 2015 Jun;100(6):2434-42. doi: 10.1210/jc.2014-3678. Epub 2015 Mar 31.

  PMID: 25825943 BACKGROUND

• Bergwall S, Johansson A, Sonestedt E, Acosta S. High versus low-added sugar consumption for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2022 Jan 5;1(1):CD013320. doi: 10.1002/14651858.CD013320.pub2.

  PMID: 34986271 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Interventions

High Fructose Corn Syrup; Sugars; Aspartame

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Sugars; Dietary Carbohydrates; Carbohydrates; Nutritive Sweeteners; Sweetening Agents; Flavoring Agents; Food Additives; Food Ingredients; Specialty Uses of Chemicals; Chemical Actions and Uses; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Peter J Havel, DVM, Ph.D

  University of California, Davis

  PRINCIPAL INVESTIGATOR

• Jean-Marc Schwarz, Ph.D.

  Touro University

  PRINCIPAL INVESTIGATOR

• Kimber L Stanhope, Ph.D.

  University of California, Davis

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2015
• First Posted: September 14, 2015
• Study Start: February 1, 2016
• Primary Completion: March 13, 2020
• Study Completion: March 13, 2020
• Last Updated: September 16, 2021

Record last verified: 2021-09

Locations

US (3)