Clinical trial NCT05291767: High Fat Meal and Postprandial TG Levels With and Without Exercise Intervention
Official title: The Effect of Moderate-Intensity Exercise on Postprandial Plasma Triglyceride Levels Following a High Fat Meal
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Ketogenic Diet
Exercise
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2022-03-23
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The objective of this study is to investigate whether "real-life" bouts of MIE are effective at attenuating PPTL after a meal (either a keto-type brownie (KETO) or a high carb (CON) meal of pasta and sauce), compared to non-exercise control. The primary outcome of this study is the measured change in PPTL level from baseline (fasting) to 6 hours postprandial on each activity level. We hypothesize that MIE will decrease PPTL in comparison to rest. For our secondary outcomes, we expect greater decrease in blood pressure, blood glucose, and metabolic rates after the MIE exercise bouts. Finally, we expect that KETO will be rated as more satiating.

Detailed description: Cardiovascular disease (CVD) is the leading cause of death and disease in the United States with an overall prevalence of about 48% in adults \>20 years of age. The Global Burden of Health assessment showed that CVD is largely attributed to dietary risks, followed by high systolic blood pressure (BP), high body mass index (BMI), high total cholesterol and fasting plasma triglycerides (TG), smoking, and inadequate physical activity. Increased plasma TG levels can promote atherosclerosis, atherosclerotic lesions, plaque formation, and heart attack. Consumption of high fat meals (HFM), which are very common in the American diet, likely increase postprandial triglyceride levels (PPTL), in proportion to the fat content of the meal. This is of particular concern because Americans, on average, have \~6 eating occasions throughout the day, thus maintaining a postprandial state of chronically high PPTL.

Additionally, a HFM has also been shown to negatively affect endothelial function, blood pressure, glycemic control, and resting metabolic rate. The decline in endothelial function is thought to be mediated by the oxidative stress caused by the elevated PPTL, which then contributes to proatherogenic state. Glycemic control was also found to be disrupted following consumption of a high fat meal likely due to a change in glucose absorption from the gut, glucose production in the liver, or glucose uptake from skeletal muscle. Conversely, blood pressure does not seem to be significantly affected by a high fat meal when measured up to 4 hours postprandial, although these findings are equivocal.

Recent studies have elucidated a potential role of exercise in attenuating the postprandial lipemia response via several proposed mechanisms including exercise-induced increase in fat oxidation, lipoprotein lipase (LPL) messenger ribonucleic acid (mRNA expression) and LPL activity, reduced hepatic VLDL secretions, and the creation of an energy deficit. LPL is responsible for breaking TGs down into free fatty acids, thus improving TG clearance rates. Exercise has also been shown to attenuate the increase in blood pressure and blood glucose caused by the high fat meal.

Previous studies have found that compared to a non-exercising control, moderate-intensity exercise (MIE) decreases PPTL by about 15.5% (p = 0.03) when performed prior to a HFM likely due to the increase in postprandial fat oxidation rate elicited by the exercise. Following exercise performed post-HFM, PPTL attenuation is believed to be due to a decrease in hepatic very low-density lipoprotein (VLDL) secretion, as studies have shown that hepatic VLDL concentrations decrease about 4.5 hours after exercising under post-absorptive conditions and circulating triglyceride (TG) levels of VLDL decrease by 30%. With the decrease in TG secretion, there is an increase in LPL activity that consequently increases TG clearance. Thus, as time between exercise bout and HFM consumption increases, LPL becomes an ever-increasingly important factor that further improves PPTL clearance. However, many studies have only investigated the effects of exercise prior to HFM consumption. Furthermore, many of these studies rely on exaggerated fat intake or energy expenditure in excess of the Physical Activity Guidelines for Americans. While there is one study that measured effects of exercise following a HFM, only moderate intensity (60% VO2peak) was used, and endothelial function was measured up to 4 hours postprandial the test meal and 2 hours following the exercise. However, the PPTL attenuation depends on the type of exercise, energy expenditure, intensity, energy balance, and timing relative to the HFM. Moderate intensity exercise (MIE), which is categorized as 65-75% of maximal heart rate, leads to an increase in glucose oxidation rates, which can potentially lead to a greater increase in fat oxidation in comparison to rest (no exercise) after a meal. While activity guidelines recommend engaging in either moderate or high intensity exercise, it remains unclear whether MIE changes PPTL differently after an HFM.

The objective of this study is to investigate whether "real-life" bouts of MIE are effective at attenuating PPTL after a meal (either a keto-type brownie (KETO) or a high carb (CON) meal of pasta and sauce), compared to non-exercise control. The primary outcome of this study is the measured change in PPTL level from baseline (fasting) to 6 hours postprandial on each activity level. We hypothesize that MIE will decrease PPTL in comparison to rest. For our secondary outcomes, we expect greater decrease in blood pressure, blood glucose, and metabolic rates after the MIE exercise bouts. Finally, we expect that KETO will be rated as more satiating.

This is a repeated measures cross-over design, in which all subjects will undergo rest (control) and two exercise protocols. The order of the exercise will be randomized using a traditional coin flip where each combination of flips results in a what meal/ exercise type the subject would be participating in that day. We will have an independent individual (not involved in the study) perform the study randomization and maintain the allocation schedule. Due to the nature of the exercise, blinding participants to the exercise intensity is not possible.

Eligibility criteria: Inclusion Criteria:

* Male or female
* 18-45 years old

Exclusion Criteria:

* Food allergies (dairy, nuts, food dyes)
* Orthopedic or musculoskeletal contraindications to exercise
* Known cardiovascular, pulmonary, or metabolic disease
* Metal implants that may interfere with bioelectrical impedance analysis
* Answers "yes" to one or more questions on the Physical Activity Readiness Questionnaire
* Current smoker
* Blood pressure of 130/80 or higher
* Meets or exceeds American College of Sports Medicine guidelines of engaging in 150min/wk of moderate intensity exercise or 75min/wk vigorous intensity exercise Unwilling or unable to follow all aspects of the study protocol
* Female participants will have to confirm that they have a normal menstrual cycle (10-12 periods per year). If yes, they are only to participate during the follicular phase of the menstrual cycle (i.e., the week following the first day of menses).

Primary outcomes:
measure: Total Blood triglyceride levels as indicated by fasting triglycerides
timeFrame: Baseline
measure: Total Blood triglyceride levels as indicated by postprandial triglycerides
timeFrame: 2 hours postprandial
measure: Total Blood triglyceride levels as indicated by postprandial triglycerides
timeFrame: 4 hours postprandial
measure: Total Blood triglyceride levels as indicated by postprandial triglycerides
timeFrame: 5 hours postprandial
measure: Total Blood triglyceride levels as indicated by postprandial triglycerides
timeFrame: 6 hours postprandial
Secondary outcomes:
measure: Blood glucose level as indicated by fasting blood glucose
timeFrame: Baseline
measure: Finger prick blood sample for blood glucose level as indicated by postprandial blood glucose
timeFrame: 2 hours postprandial
measure: Finger prick blood sample for blood glucose level as indicated by postprandial blood glucose
timeFrame: 4 hours postprandial
measure: Finger prick blood sample for blood glucose level as indicated by postprandial blood glucose
timeFrame: 5 hours postprandial
measure: Finger prick blood sample for blood glucose level as indicated by postprandial blood glucose
timeFrame: 6 hours postprandial
measure: Systolic and diastolic Blood pressure
timeFrame: Baseline to 6 hours postprandial in 15 minute increments
measure: Indirect Calorimetry: Resting Metabolic Rate
timeFrame: Baseline
measure: Indirect Calorimetry: Resting Metabolic Rate
timeFrame: 2 hour postprandial
measure: Indirect Calorimetry: Resting Metabolic Rate
timeFrame: 3 hour postprandial
measure: Indirect Calorimetry: Resting Metabolic Rate
timeFrame: 4 hour postprandial
measure: Indirect Calorimetry: Resting Metabolic Rate
timeFrame: 5 hour postprandial
measure: Indirect Calorimetry: Resting Metabolic Rate
timeFrame: 6 hour postprandial
measure: Indirect Calorimetry: Respiratory Exchange Ratio
timeFrame: Baseline
measure: Indirect Calorimetry: Respiratory Exchange Ratio
timeFrame: 2 hours postprandial
measure: Indirect Calorimetry: Respiratory Exchange Ratio
timeFrame: 3 hours postprandial
measure: Indirect Calorimetry: Respiratory Exchange Ratio
timeFrame: 4 hours postprandial
measure: Indirect Calorimetry: Respiratory Exchange Ratio
timeFrame: 5 hours postprandial
measure: Indirect Calorimetry: Respiratory Exchange Ratio
timeFrame: 6 hours postprandial
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
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