High Protein Diet for Atherosclerosis

(HPA Trial)

Recruiting at 2 trial locations

Overseen By Babak Razani, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Missouri-Columbia

Must not be taking: Medications, supplements confounding outcomes

Disqualifiers: Organ dysfunction, Alcohol use disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day per meal type

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial looks at how eating a lot of protein affects plaque buildup in arteries, which can lead to heart attacks and strokes. It focuses on adults in Western societies who eat a lot of protein. The study suggests that animal proteins might be worse because they interfere with cell cleaning processes, leading to more plaque.

Will I have to stop taking my current medications?

The trial excludes participants who use medications or dietary supplements that could affect the study outcomes, so you may need to stop taking certain medications. It's best to discuss your specific medications with the trial coordinators.

What data supports the effectiveness of a high-protein diet as a treatment for atherosclerosis?

Research suggests that high-protein diets can help with weight loss and improve certain heart health markers like triglycerides and blood pressure. However, the overall effect on atherosclerosis risk is unclear, and some studies show that high-protein diets might worsen certain heart disease risk factors. ^{1 2 3 4 5}

Is a high protein diet safe for humans?

Some studies suggest that high protein diets, especially from plant sources, may reduce blood pressure and prevent cardiovascular disease. However, long-term high protein intake, particularly from animal sources, may lead to health issues like bone and kidney disorders, increased cancer risk, and progression of heart disease. It's important to consider the source of protein and consult with a healthcare provider. ^{6 7 8 9 10}

How does a high protein diet differ from other treatments for atherosclerosis?

A high protein diet, particularly one with a focus on animal protein, may differ from other treatments for atherosclerosis by potentially increasing the risk of atherosclerotic lesions, as opposed to diets rich in vegetal protein and starch which are associated with less lesion involvement. This approach contrasts with traditional dietary recommendations that emphasize reducing cholesterol and fat intake to prevent atherosclerosis. ^{11 12 13 14 15}

Research Team

Bettina Mittendorfer

Principal Investigator

University of Missouri-Columbia

Eligibility Criteria

This trial is for adults aged 45-75 with a BMI of 25.0 to less than 40.0 kg/m2, who do not smoke and have no significant organ dysfunction or allergies to meal ingredients. It excludes those on certain medications or supplements, highly active individuals, alcohol users with disorders, premenopausal women, prisoners, and anyone unable to consent.

Inclusion Criteria

Your body mass index is between 25 and 40.

I am between 45 and 75 years old.

Exclusion Criteria

Your blood triglyceride level is less than 125 mg/dl.

prisoners

You exercise regularly for more than 150 minutes each week.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive different dietary protein meals to study the impact on macrophage mTOR signaling and atherosclerosis

1 day per meal type

1 visit per meal type (in-person)

Follow-up

Participants are monitored for changes in monocyte p-S6 content and other cardiovascular markers

4 weeks

Treatment Details

Interventions

• High Protein Diet

Trial Overview The study tests the effects of different diets on atherosclerosis: high plant protein meals (with and without extra leucine), standard meals, and high animal protein meals. The focus is on how these diets might influence heart disease by affecting plaque in arteries.

Participant Groups

Group I: High plant protein meal with additional leucine Experimental Treatment 1 Intervention

Group II: High plant protein meal Experimental Treatment 1 Intervention

Group III: High animal protein meal Experimental Treatment 1 Intervention

Group IV: Standard meal Active Control 1 Intervention

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Findings from Research

High-protein diets (25%-35% of energy) are effective for weight loss and are more satiating than diets high in carbohydrates or fats, leading to lower serum triglyceride levels.

The impact of high-protein diets on cholesterol levels varies based on carbohydrate restriction and saturated fat intake, with some individuals experiencing an increase in low-density lipoprotein cholesterol despite weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic effects of high-protein diets. Clifton, PM., Keogh, J.[2022]

In a study of 26 individuals over one year, those who followed a prescribed treatment and dietary guidelines showed significant regression of coronary artery disease (CAD) and recovery of viable heart tissue, with 43.75% of myocardial segments improving.

Conversely, individuals on a high-protein diet experienced worsening of key risk factors and a 39.7% progression in CAD, suggesting that such diets may negatively impact heart health by increasing inflammation and lipid deposition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of high-protein diets on coronary blood flow. Fleming, RM.[2017]

A study on rats showed that a low protein diet (10% casein) led to increased plasma triglycerides and higher platelet aggregability, which are risk factors for atherosclerosis and thrombosis, compared to moderate (20% casein) and high protein (60% casein) diets.

The low protein group produced more thromboxane A2 (which promotes clotting) and less prostaglandin I2 (which prevents clotting), suggesting that higher protein intake may help reduce the risk of arterial thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of dietary protein level on platelet aggregation in rat. Morita, I., Takahashi, R., Ebisawa, H., et al.[2019]

Higher-protein diets (1.2 to 1.6 g protein per kg of body weight per day) have been shown to lead to greater weight loss, fat mass loss, and preservation of lean mass compared to lower-protein diets, based on several meta-analyses of short-term studies.

While short-term studies consistently show benefits of higher protein intake, longer-term studies yield mixed results, primarily due to dietary compliance; those who adhered to higher-protein diets experienced significant improvements in body weight and cardiometabolic risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of protein in weight loss and maintenance. Leidy, HJ., Clifton, PM., Astrup, A., et al.[2023]

In a study analyzing data from the Cholesterol Lowering Atherosclerosis Study, increased consumption of total fat and polyunsaturated fat was linked to a higher risk of developing new atherosclerotic lesions over two years.

When participants reduced their fat intake, they compensated by increasing dietary protein and carbohydrates, suggesting that these substitutes may be more beneficial than replacing fats with other types of fats in preventing new lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of diet on the appearance of new lesions in human coronary arteries. Blankenhorn, DH., Johnson, RL., Mack, WJ., et al.[2016]

Recent studies indicate that higher protein intake, especially from plant sources, may lower blood pressure and reduce the risk of cardiovascular diseases, contrasting previous assumptions about protein's negative effects.

Epidemiological evidence suggests that increased protein consumption is linked to lower blood pressure over time and a reduced risk of ischemic heart disease, although more compelling data is needed before making dietary recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of protein intake on blood pressure and cardiovascular disease. Appel, LJ.[2019]

In a study of 215 obese adults over 12 weeks, a high protein (HP) diet led to greater reductions in triglycerides and total cholesterol compared to a standard protein (SP) diet, indicating improved lipid profiles for cardiovascular disease (CVD) risk.

While overall weight loss was similar between the HP and SP diets, individuals with higher baseline triglyceride levels experienced significantly greater weight loss and fat loss on the HP diet, suggesting it may be particularly beneficial for those at increased risk of CVD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High protein diets decrease total and abdominal fat and improve CVD risk profile in overweight and obese men and women with elevated triacylglycerol. Clifton, PM., Bastiaans, K., Keogh, JB.[2015]

In a study of 29,017 postmenopausal women followed for 15 years, substituting vegetable protein for carbohydrates was linked to a 30% reduction in coronary heart disease (CHD) mortality, suggesting that plant-based proteins may be healthier than carbohydrates.

Conversely, higher intake of red meats and dairy products was associated with increased CHD mortality, indicating that not all protein sources are equally beneficial and that long-term high-protein diets could have negative health effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations of dietary protein with disease and mortality in a prospective study of postmenopausal women. Kelemen, LE., Kushi, LH., Jacobs, DR., et al.[2023]

A high protein diet was found to reduce the incidence of stroke, with high fish protein specifically helping to lower severe hypertension, while high soybean protein did not have the same effect.

Certain amino acids, particularly lysine, threonine, isoleucine, leucine, and methionine, were linked to the reduced risk of stroke and the antihypertensive effects of high protein diets, suggesting that these amino acids may play a key role in the protective benefits of such diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prophylactic trials for stroke in stroke-prone SHR. (3) Amino acid analysis of various diets and their prophylactic effect. Yamori, Y., Horie, R., Ohtaka, M., et al.[2023]

High protein diets, exceeding the recommended dietary allowance of 0.8 g protein/kg body weight/day, are associated with several potential health risks, including bone disorders, renal dysfunction, increased cancer risk, liver issues, and progression of coronary artery disease, based on a review of 32 studies involving healthy adults.

The review suggests that there is insufficient scientific evidence to support the recommendation of high protein intake for healthy adults, highlighting the need for further research, particularly large randomized controlled trials, to better understand the long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Effects Associated with Protein Intake above the Recommended Dietary Allowance for Adults. Delimaris, I.[2021]

In a study involving 32 male Wistar rats over 8 weeks, dietary supplementation with the nonpolar amino acids valine and leucine significantly reduced serum cholesterol levels in a high-fat diet context.

The reduction in cholesterol levels also helped mitigate the prooxidant status induced by hypercholesterolemia, suggesting that these amino acids may be beneficial in reducing the risk of atherosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effects of some nonpolar aminoacids--valine, leucine--administration on the arterial wall already exposed to a hypercholesterolemic diet]. Cojocaru, E., Zamfir, CL., Lupuşoru, CE., et al.[2015]

In a study of dietary habits from 253 deceased New Orleans men, higher intakes of plant-based proteins, carbohydrates, starch, and fiber were linked to less severe atherosclerotic lesions in coronary arteries, suggesting a protective effect against heart disease.

Conversely, diets high in animal protein and fat were associated with greater atherosclerotic involvement, indicating that a diet rich in plant-based foods may contribute to better cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary-atherosclerosis study on deceased persons. Relation of selected dietary components to raised coronary lesions. Moore, MC., Guzmán, MA., Schilling, PE., et al.[2022]

The study found that a high-fat plus high-cholesterol diet in Göttingen Miniature Swine led to significant atherosclerosis development, with lesions observed as early as one month and worsening by nine months, indicating the diet's strong impact on cardiovascular health.

The lesions observed in the swine were similar to those found in humans, suggesting that these swine can serve as a valuable model for studying atherosclerosis and its relationship with hypercholesterolemia and hyper-beta-lipoproteinemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Göttingen miniature swine as a model for diet-induced atherosclerosis]. Tanigawa, M., Akaike, I., Adachi, J., et al.[2019]

A diet plays a crucial role in preventing atherosclerosis, a condition characterized by the buildup of fats and cholesterol in arteries.

New functional meat foods have been developed that contain significantly lower cholesterol levels compared to traditional meat, making them a promising option for atherosclerosis prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Functional meat food in atherosclerosis prevention]. Chernobel'skiĭ, GN., Davletbaev, RM., Sazonova, EN., et al.[2006]

A study suggests that diet may be linked to the prevalence of atherosclerosis, particularly in wealthier countries, highlighting the need for systematic comparisons between high-risk and low-risk areas.

The research focuses on five Central European countries, where Austria, Czechoslovakia, and Hungary have high ischemic heart disease mortality rates, while Poland and Romania have lower rates, indicating that dietary differences could help identify potential causes of atherosclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet and atherogenesis. Seely, S.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Metabolic effects of high-protein diets. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The effect of high-protein diets on coronary blood flow. [2017]

3. Scotland pubmed.ncbi.nlm.nih.gov

Effect of dietary protein level on platelet aggregation in rat. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

The role of protein in weight loss and maintenance. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

The influence of diet on the appearance of new lesions in human coronary arteries. [2016]

6. England pubmed.ncbi.nlm.nih.gov

The effects of protein intake on blood pressure and cardiovascular disease. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

High protein diets decrease total and abdominal fat and improve CVD risk profile in overweight and obese men and women with elevated triacylglycerol. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Associations of dietary protein with disease and mortality in a prospective study of postmenopausal women. [2023]

9. Japan pubmed.ncbi.nlm.nih.gov

Prophylactic trials for stroke in stroke-prone SHR. (3) Amino acid analysis of various diets and their prophylactic effect. [2023]

10. Egypt pubmed.ncbi.nlm.nih.gov

Adverse Effects Associated with Protein Intake above the Recommended Dietary Allowance for Adults. [2021]

11. Romania pubmed.ncbi.nlm.nih.gov

[The effects of some nonpolar aminoacids--valine, leucine--administration on the arterial wall already exposed to a hypercholesterolemic diet]. [2015]

12. United States pubmed.ncbi.nlm.nih.gov

Dietary-atherosclerosis study on deceased persons. Relation of selected dietary components to raised coronary lesions. [2022]

13. Japan pubmed.ncbi.nlm.nih.gov

[Göttingen miniature swine as a model for diet-induced atherosclerosis]. [2019]

14. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Functional meat food in atherosclerosis prevention]. [2006]

15. United States pubmed.ncbi.nlm.nih.gov

Diet and atherogenesis. [2019]