Adverse Metabolic Effects of Dietary Sugar

NCT ID: NCT02548767

Last Updated: 2021-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2020-03-13

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.

Detailed Description

Recent studies have demonstrated that consuming high fructose corn syrup (HFCS)- or sucrose-sweetened beverages increased lipid/lipoprotein risk factors for cardiovascular disease (CVD) in healthy adults compared with iso-caloric amounts of glucose or low-fat milk. The longest of these studies, which utilized a 6-month intervention, also showed increased liver and muscle TG and increased visceral adipose deposition. Neither of these studies found differences in weight gain between subjects consuming HFCS/sucrose beverages compared with control beverages. These results suggest that it is not just excess calories and weight gain that mediate the effects of dietary sugar/fructose on the development of metabolic disease; rather, dietary sugar per se is also a contributor. However, it is not known whether consumption of excessive amounts of sugar can increase risk factors for metabolic disease in the absence of positive energy balance and weight gain, nor whether the adverse effects of sugar consumption are exacerbated by weight gain. This study will compare the contribution of sugar with the contribution of energy level to the increases in risk factors for metabolic disease induced by consumption of HFCS-sweetened beverages under energy-balanced or ad libitum conditions. The investigators will measure risk factors and processes associated with metabolic disease in 4 groups of young, healthy adults who will consume 1) 0%, 2) or 25% of energy requirement as HFCS-sweetened beverages for 8 weeks with an energy-balanced diet for 6 weeks; 3) 0%, or 4) 25% of energy requirement as HFCS-sweetened beverages for 8 weeks with an ad libitum diet for 6 weeks. All diets, formulated to achieve a comparable macronutrient intake (55% energy as carbohydrate, 35% fat, 15% protein) among all 4 experimental groups, will be provided to the subjects throughout the entire study. The investigators hypothesize that under energy balanced (EB) condition that prevent body weight gain, consumption of HFCS-sweetened beverages will result in adverse metabolic effects compared with aspartame-sweetened beverages. Consumption of HFCS-sweetened beverages with the ad libitum (AL) diet will result in increased energy intake and body weight gain compared with aspartame-sweetened beverages, and will also result in adverse metabolic effects that are more marked than with consumption of HFCS-sweetened beverages with the energy-balanced diet. These results will demonstrate that consumption of HFCS-sweetened beverages increases risk for metabolic disease both directly, via the adverse effects of fructose on lipid and carbohydrate metabolism, and indirectly, via the effects of HFCS-sweetened beverages to promote excess energy intake and body weight gain. These findings will have the potential to influence dietary guidelines and public health policy.

Conditions

Chronic Disease of Cardiovascular System; Type 2 Diabetes; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

HFCS-EB

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.

Group Type: EXPERIMENTAL

high fructose corn syrup

Intervention Type: OTHER

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

Energy-balanced diet

Intervention Type: 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.

Asp-EB

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.

Group Type: PLACEBO_COMPARATOR

aspartame

Intervention Type: OTHER

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

Energy-balanced diet

Intervention Type: 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.

HFCS-AL

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.

Group Type: EXPERIMENTAL

high fructose corn syrup

Intervention Type: OTHER

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

Ad libitum diet

Intervention Type: 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.

Asp-AL

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.

Group Type: PLACEBO_COMPARATOR

aspartame

Intervention Type: OTHER

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

Ad libitum diet

Intervention Type: 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.

Interventions

high fructose corn syrup

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

Intervention Type: OTHER

aspartame

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

Intervention Type: OTHER

Energy-balanced diet

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.

Intervention Type: OTHER

Ad libitum diet

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.

Intervention Type: OTHER

Other Intervention Names

sugar, HFCS, high fructose corn syrup-55, HFCS-55; non-caloric sweetener; Weight-maintaining diet; Positive-energy diet

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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
• Diet exclusions: Food allergies, special dietary restrictions, food allergies, routine consumption of less than 3 meals/day, routine ingestion of more than 2 sugar-sweetened beverages or 1 alcoholic beverage/day, unwillingness to consume any food on study menu
• Hydrogen concentration in breath sample following consumption of HFCS-beverage during screening >50ppm
• Veins that are assessed by the CCRC (Clinical Research Center) R.N.s as being unsuitable for long-term infusions and multiple blood draws from a catheter.
• Pre-existing claustrophobia or metal implants that preclude MRI

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Touro University, California

OTHER

Sponsor Role: collaborator

University of Southern California

OTHER

Sponsor Role: collaborator

USDA, Western Human Nutrition Research Center

FED

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter J Havel, DVM, Ph.D

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Jean-Marc Schwarz, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Touro University

Kimber L Stanhope, Ph.D.

Role: STUDY_DIRECTOR

University of California, Davis

Locations

University of California, Davis

Davis, California, United States

Clinical Research Center

Sacramento, California, United States

Touro University California Translational Research Clinic and Student Health Clinic

Vallejo, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 23594708 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22828276 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21952692 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21849529 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22034869 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19381015 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22205311 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22933433 (View on PubMed)

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.

Reference Type: BACKGROUND

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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.

Reference Type: DERIVED

PMID: 34986271 (View on PubMed)

Other Identifiers

1R01HL121324

Identifier Type: NIH

Identifier Source: secondary_id

View Link

499106

Identifier Type: -

Identifier Source: org_study_id