Dietary Protein and Monocyte/Macrophage Mammalian Target of Rapamycin (mTOR) Signaling

NCT ID: NCT03946774

Last Updated: 2024-10-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-01
• Study Completion Date: 2023-05-04

Brief Summary

High protein low carbohydrate diets have become popular in recent years to help facilitate weight loss. It is controversial if these diets are associated with an increased risk of cardiovascular disease.

The investigators propose to administer high and low protein shakes to participants and measure effects on circulating monocytes, immune cells critical to the development of atherosclerosis and cardiovascular disease. In order to study circulating monocytes, blood will be collected from the study participants just prior to drinking the shake, and then 1 and 4 hours after drinking the shake.

In order to assess functional effects on monocytes, investigators will perform a series of assays comparing the results between individuals who drank high protein vs low protein shakes.

Detailed Description

Cardiovascular disease remains the leading cause of death globally with obesity as of one of the dominant modifiable risk factors. Obesity is also a precursor to several other cardiovascular risk factors including hypertension, hyperlipidemia, and diabetes. Almost all weight loss efforts utilize dietary modification with high protein/low carbohydrate diets serving as one of the most popular approaches. Despite the metabolic benefits of high dietary protein, recent studies have raised a concerning association with increased risk of atherosclerosis and cardiovascular disease. Although this remains controversial, there is some animal data showing evidence of dietary protein's proatherogenic role. These data are correlative and no mechanistic studies have been undertaken.

The downstream events after protein ingestion involve digestion of the protein into amino acids, increases in blood amino acids, and distribution to target tissues. Mouse models have definitively shown that circulating monocytes and macrophages of arterial blood vessels are particularly sensitive to this amino acid load with robust activation of the mTOR (mammalian target of rapamycin) signaling pathway. This in turn leads to inhibition of essential degradative processes of the macrophage such as autophagy and promotes release of pro-inflammatory cytokines. Thus, macrophage function in vascular beds becomes pathogenic leading to atherogenesis and cardiovascular disease

The translation of these mechanistic studies in animal models to human is the next obvious step in this research. However, no studies have elucidated the mechanisms of monocyte activation and function following administration of high dietary protein in humans. The investigators propose a pilot study to bridge an important gap in translational research which will elucidate the mechanisms by which dietary protein affects human monocyte function and the risk of atherosclerotic plaque formation. Specifically, the investigators will evaluate the acute activation of mTOR signaling and downstream sequelae in circulating monocytes following the administration of protein shakes. This study will address the hypothesis that humans exposed to high dietary protein will have significantly higher post-prandial monocyte mTOR activation with concomitant development of impaired degradative capacity and a proinflammatory state.

An understanding of these mechanisms has broad implications in the evaluation and future therapeutic interventions of cardiovascular disease.

In addition, this can provide a valuable clinical tool for health care providers in educating patients on dietary changes to ameliorate cardiovascular risk.

Conditions

Dietary Protein

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

High protein

Subjects getting high protein shake

Group Type: ACTIVE_COMPARATOR

Dietary protein shake

Intervention Type: DIETARY_SUPPLEMENT

It is a milk based protein shake. Ingredients include a combination of the following depending on protein content: Boost Plus (a commercial supplement), Unjury (a commercial whey protein isolate), nonfat dry milk powder, Sol Carb (commercial supplement composed of a carbohydrate polymer), canola oil, and water.

In order to ensure consistency across all participants each beverage will be prepared in the Clinical Translational Research Unit Metabolic Kitchen under the supervision of a registered dietitian prior to the study participant's visit. Ingredients are individually weighed on a food scale by metabolic kitchen staff to the nearest 0.1 g and then mixed using a magnetic stir plate.

Nutritional breakdown of the smoothies (high versus low protein):

High protein drink nutrition: 500 kcal per serving, 50% protein, 17% fat, and 36% carbohydrate.

Low (standard) protein drink nutrition: 500 kcal per serving, 10% protein, 17% fat, and 73% carbohydrate.

Low protein

Subjects getting low protein shake

Group Type: ACTIVE_COMPARATOR

Dietary protein shake

Intervention Type: DIETARY_SUPPLEMENT

It is a milk based protein shake. Ingredients include a combination of the following depending on protein content: Boost Plus (a commercial supplement), Unjury (a commercial whey protein isolate), nonfat dry milk powder, Sol Carb (commercial supplement composed of a carbohydrate polymer), canola oil, and water.

In order to ensure consistency across all participants each beverage will be prepared in the Clinical Translational Research Unit Metabolic Kitchen under the supervision of a registered dietitian prior to the study participant's visit. Ingredients are individually weighed on a food scale by metabolic kitchen staff to the nearest 0.1 g and then mixed using a magnetic stir plate.

Nutritional breakdown of the smoothies (high versus low protein):

High protein drink nutrition: 500 kcal per serving, 50% protein, 17% fat, and 36% carbohydrate.

Low (standard) protein drink nutrition: 500 kcal per serving, 10% protein, 17% fat, and 73% carbohydrate.

Interventions

Dietary protein shake

It is a milk based protein shake. Ingredients include a combination of the following depending on protein content: Boost Plus (a commercial supplement), Unjury (a commercial whey protein isolate), nonfat dry milk powder, Sol Carb (commercial supplement composed of a carbohydrate polymer), canola oil, and water.

In order to ensure consistency across all participants each beverage will be prepared in the Clinical Translational Research Unit Metabolic Kitchen under the supervision of a registered dietitian prior to the study participant's visit. Ingredients are individually weighed on a food scale by metabolic kitchen staff to the nearest 0.1 g and then mixed using a magnetic stir plate.

Nutritional breakdown of the smoothies (high versus low protein):

High protein drink nutrition: 500 kcal per serving, 50% protein, 17% fat, and 36% carbohydrate.

Low (standard) protein drink nutrition: 500 kcal per serving, 10% protein, 17% fat, and 73% carbohydrate.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

1. 18+ years of age

2. Able to drink milk based protein shake

Exclusion Criteria

1. Current Pregnancy

2. Any food allergies

3. Personal Hx of Diabetes

4. Personal Hx of Heart Disease

5. Personal Hx of High blood pressure

6. Personal Hx of Stroke

7. Personal Hx of Cancer

8. Personal Hx of Organ transplant

9. Taking Rapamycin/Sirolimus

10. Taking Torisel/Temsirolimus

11. Taking Afinitor/Everolimus

12. Taking any statin medication (eg.simvastatin/atorvastatin/rosuvastatin etc)

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

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Washington University

St Louis, Missouri, United States

Countries

United States

Other Identifiers

201808084

Identifier Type: -

Identifier Source: org_study_id