Dietary Protein Sources and Atherogenic Dyslipidemia

NCT01427855 | Completed DMC

• 1 other identifier: 1R01HL106003-01A1
• Study Type: interventional
• Target: 113
• Locations: 1 country
• Sites: 1

Brief Summary

There is growing epidemiological evidence that consumption of red meat is associated with greater incidence of Cardiovascular Disease (CVD) than either white meat or non-meat foods. Research from our group has shown that a high saturated fat (SF) diet with a moderate red meat content selectively increases intermediate density lipoproteins (IDL) and larger low density lipoproteins (LDLs), which are more weakly associated with CVD risk than smaller LDLs. In contrast, the investigators have found that with a similar intake of SF, high beef consumption results in a preferential increase in small and medium LDL particles that are strongly related to CVD. To date, no studies have directly compared the lipoprotein effects of red meat with that of other food sources of protein in the context of both high and low saturated fat intake. The overall objective of this project is to test the hypothesis that the effects of SF on lipoprotein markers of CVD risk are influenced by sources of dietary protein. The investigators hypothesize that adverse effects of SF on plasma levels of LDL-cholesterol (C), apolipoprotein B (apo B), and atherogenic LDL particles are greater in a diet with a high content of red meat than in diets in which the major proteins are from white meat (poultry) or non-meat sources. The investigators propose a clinical trial in which 180 healthy men and women will be randomized to high SF or low SF diet groups, and within each group, consume diets with equivalent amounts of protein from red meat, white meat, and non-meat sources for 4 wks each in random order. Specifically, the investigators will test whether: (1) With high SF, the red meat diet, compared to the other protein sources, will result in higher levels of LDL-C, apoB, small and medium LDL, and total/high density lipoprotein (HDL)C; (2) With low SF, dietary protein source will not be related to any of these measurements; (3) With both the white meat and non-meat protein diets, increased LDL-C with high vs. low SF will be due primarily to increases in large LDL, whereas with red meat the additional increase in small and medium LDL will result in greater increases in plasma apoB and total LDL particle number. Aim 4 will test hypotheses that increases in small and medium LDL with high SF plus red meat are related to increased activity of hepatic lipase, a key determinant of small LDL production, and that increases in large LDL induced by high SF are related to suppression of LDL receptors. The investigators will also assess the effects of protein source and saturated fat content on markers of insulin resistance, inflammation and endothelial function.

Conditions

Cardiovascular Disease; Dyslipidemia; Insulin Resistance; Inflammation

Keywords

Dietary Protein; Red Meat; White Meat; Vegetable Protein; Saturated Fat; LDL Subclasses; Cholesterol; Atherogenic Dyslipidemia

Outcome Measures

Primary Outcomes (4)

• Change from baseline in LDL-Cholesterol

  6 weeks, 12 weeks, 18 weeks

• Change from baseline in ApoB

  6 weeks, 12 weeks, 18 weeks

• Change from baseline in Small + Medium Sized LDL

  6 weeks, 12 weeks, 18 weeks

• Change from baseline in Total Cholesterol/HDL Cholesterol ratio

  6 weeks, 12 weeks, 18 weeks

Secondary Outcomes (12)

• Change from baseline in HDL-Cholesterol

  6 weeks, 12 weeks, 18 weeks

• Change from baseline in non-HDLC

  6 weeks, 12 weeks, 18 weeks

• Change from baseline in apoAI

  6 weeks, 12 weeks, 18 weeks

• Change from baseline in apoAII

  6 weeks, 12 weeks, 18 weeks

• Change from baseline in HDL2 Cholesterol

  6 weeks, 12 weeks, 18 weeks

Study Arms (6)

High Saturated Fat Red Meat Diet

EXPERIMENTAL

Other: High saturated fat red meat diet

High Saturated Fat White Meat Diet

EXPERIMENTAL

Other: High saturated fat white meat diet

High Saturated Fat Non-Meat Diet

EXPERIMENTAL

Other: High saturated fat non-meat diet

Low Saturated Fat Red Meat Diet

EXPERIMENTAL

Other: Low saturated fat red meat diet

Low Saturated Fat White Meat Diet

EXPERIMENTAL

Other: Low saturated fat white meat diet

Low Saturated Fat Non-Meat Diet

EXPERIMENTAL

Other: Low saturated fat non meat diet

Interventions

High saturated fat red meat diet OTHER

4 weeks of a high saturated fat red meat diet (38% carbohydrate; 25% protein (12% kcal from red meat protein); 37% fat (15% kcal from saturated fat))

High Saturated Fat Red Meat Diet

High saturated fat non-meat diet OTHER

4 weeks of a high saturated fat non-meat diet (38% carbohydrate; 25% protein (16% kcal from non-meat protein); 37% fat (15% kcal from saturated fat))

High Saturated Fat Non-Meat Diet

High saturated fat white meat diet OTHER

4 weeks of a high saturated fat white meat diet (38% carbohydrate; 25% protein (12% kcal from white meat protein); 37% fat (15% kcal from saturated fat))

High Saturated Fat White Meat Diet

Low saturated fat red meat diet OTHER

4 weeks of a low saturated fat red meat diet (38% carbohydrate; 25% protein (12% kcal from red meat protein); 37% fat (7% kcal from saturated fat))

Low Saturated Fat Red Meat Diet

Low saturated fat white meat diet OTHER

4 weeks of a low saturated fat white meat diet (38% carbohydrate; 25% protein (12% kcal from white meat protein); 37% fat (7% kcal from saturated fat))

Low Saturated Fat White Meat Diet

Low saturated fat non meat diet OTHER

4 weeks of a low saturated fat non-meat diet (38% carbohydrate; 25% protein (16% kcal from non-meat protein); 37% fat (7% kcal from saturated fat))

Low Saturated Fat Non-Meat Diet

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old
• Non-smoking
• Agrees to abstain from alcohol and dietary supplements during the study
• Willing to consume all study foods as instructed

You may not qualify if:

• History of heart disease, cerebrovascular disease, peripheral vascular disease, bleeding disorder, liver or renal disease, lung disease, diabetes, Human immunodeficiency virus (HIV), or cancer (other than skin cancer) in the last 5 years
• Body mass index (BMI) \> 35 kg/m2 or \< 20 kg/m2
• Not weight stable
• Abnormal thyroid stimulating hormone
• Blood pressure \> 150/90
• Fasting blood sugar \>126 mg/dl
• Fasting triglyceride levels \>500 mg/dl
• Total- and LDL cholesterol \>95th percentile for age and sex
• Pregnant or breastfeeding
• Taking hormones or drugs known to affect lipid metabolism

Sponsors & Collaborators

• UCSF Benioff Children's Hospital Oakland: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Cholesterol Research Center, Children's Hospital Research Institute

Berkeley, California, 94705, United States

Location

Related Publications (2)

• Ferrell M, Bazeley P, Wang Z, Levison BS, Li XS, Jia X, Krauss RM, Knight R, Lusis AJ, Garcia-Garcia JC, Hazen SL, Tang WHW. Fecal Microbiome Composition Does Not Predict Diet-Induced TMAO Production in Healthy Adults. J Am Heart Assoc. 2021 Nov 2;10(21):e021934. doi: 10.1161/JAHA.121.021934. Epub 2021 Oct 29.

  PMID: 34713713 DERIVED

• Bergeron N, Chiu S, Williams PT, M King S, Krauss RM. Effects of red meat, white meat, and nonmeat protein sources on atherogenic lipoprotein measures in the context of low compared with high saturated fat intake: a randomized controlled trial. Am J Clin Nutr. 2019 Jul 1;110(1):24-33. doi: 10.1093/ajcn/nqz035.

  PMID: 31161217 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Dyslipidemias; Insulin Resistance; Inflammation

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ronald M Krauss, MD

  UCSF Benioff Children's Hospital Oakland

  PRINCIPAL INVESTIGATOR

• Nathalie Bergeron, PhD

  Children's Hospital Oakland Research Institiute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2011
• First Posted: September 2, 2011
• Study Start: January 1, 2012
• Primary Completion: November 1, 2016
• Study Completion: May 1, 2017
• Last Updated: November 24, 2020

Record last verified: 2020-11

Locations

US (1)