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Adverse Metabolic Effects of Dietary Sugar

רק משתמשים רשומים יכולים לתרגם מאמרים
התחבר הרשם
הקישור נשמר בלוח
סטָטוּסגיוס
נותני חסות
University of California, Davis
משתפי פעולה
Touro University, California
University of Southern California
USDA, Western Human Nutrition Research Center
National Heart, Lung, and Blood Institute (NHLBI)

מילות מפתח

תַקצִיר

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.

תיאור

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.

תאריכים

אומת לאחרונה: 05/31/2020
הוגש לראשונה: 05/25/2015
ההרשמה המשוערת הוגשה: 09/09/2015
פורסם לראשונה: 09/13/2015
העדכון האחרון הוגש: 06/02/2020
עדכון אחרון פורסם: 06/04/2020
תאריך תחילת לימוד בפועל: 01/31/2016
תאריך סיום משוער משוער: 02/28/2021
תאריך סיום משוער ללימודים: 02/28/2021

מצב או מחלה

Chronic Disease of Cardiovascular System
Type 2 Diabetes
Obesity

התערבות / טיפול

Other: high fructose corn syrup

Other: aspartame

Other: Energy-balanced diet

Other: Ad libitum diet

שלב

-

קבוצות זרועות

זְרוֹעַהתערבות / טיפול
Experimental: 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.
Placebo Comparator: 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.
Experimental: 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.
Placebo Comparator: 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.

קריטריונים לזכאות

גילאים הזכאים ללימודים 18 Years ל 18 Years
מינים הזכאים ללימודיםAll
מקבל מתנדבים בריאיםכן
קריטריונים

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

תוֹצָאָה

מדדי תוצאות ראשוניים

1. Change of de novo lipogenesis: palmitate tracer-to-tracee ratios by gas chromatography-mass spectrometry. [22 hours at Baseline and 4-week Intervention]

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.

אמצעי תוצאה משניים

1. Change of endogenous glucose production measured by standard dilution techniques [7 hours at Baseline and 4-week Intervention]

Blood samples are collected during isotopic glucose infusion, and endogenous glucose production (glucose appearance) is measured by standard dilution techniques.

2. Change of whole body insulin sensitivity [3 hours at Baseline and 4-week Intervention]

A variable 20% glucose infusion is adjusted to maintain euglycemia during insulin infusion in order to determine insulin-mediated glucose uptake.

3. Change of liver lipid [Baseline, 4-week Intervention and 8-week intervention]

Quantified from magnetic resonance imaging

4. Change of fat oxidation [17 hours at Baseline and 4-week Intervention]

Fat oxidation is calculated from measures of oxygen consumption and carbon dioxide production by indirect calorimetry.

5. Change of Very low density lipoprotein (VLDL)-triglyceride (TG) kinetics [22 hours at Baseline and 4-week Intervention]

During overnight fasting VLDL-TG kinetics will be determined using a prime constant infusion of isotopic glycerol. During the meal-feeding protocol, the washout kinetic enrichment of isotopic glycerol in the TG will be used to estimate VLDL-TG with a non-steady modeling approach.

אמצעי תוצאה אחרים

1. Change of blood levels of LDL-cholesterol [Baseline and 4-week Intervention]

fasting and postprandial plasma concentrations of TG, cholesterol, low density lipoprotein cholesterol, apolipoprotein B, apolipoprotein C3 are measured

2. Change of blood levels of non-HDL-cholesterol [Baseline and 4-week Intervention]

fasting and postprandial plasma concentrations of TG, cholesterol, low density lipoprotein cholesterol, apolipoprotein B, apolipoprotein C3 are measured

3. Change of blood levels of apolipoprotein B [Baseline and 4-week Intervention]

fasting and postprandial plasma concentrations of TG, cholesterol, low density lipoprotein cholesterol, apolipoprotein B, apolipoprotein C3 are measured

4. Change of blood levels of triglyceride [Baseline and 4-week Intervention]

fasting and postprandial plasma concentrations of TG, cholesterol, low density lipoprotein cholesterol, apolipoprotein B, apolipoprotein C3 are measured

5. Change of blood levels of apolipoprotein C3 [Baseline and 4-week Intervention]

fasting and postprandial plasma concentrations of TG, cholesterol, low density lipoprotein cholesterol, apolipoprotein B, apolipoprotein C3 are measured

6. Change of blood levels of uric acid [Baseline and 4-week Intervention]

fasting and postprandial plasma concentrations of uric acid are measured

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