High Protein Diet for Atherosclerosis
(HPA Trial)
Recruiting in Palo Alto (17 mi)
+2 other locations
Overseen byBettina Mittendorfer
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Missouri-Columbia
Must not be taking: Medications, supplements confounding outcomes
Disqualifiers: Organ dysfunction, Alcohol use disorder, others
No Placebo Group
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.
12345Is 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.
678910How 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.
1112131415Eligibility 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.
+9 more
Trial 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
Participant Groups
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.
4Treatment groups
Experimental Treatment
Active Control
Group I: High plant protein meal with additional leucineExperimental Treatment1 Intervention
Group II: High plant protein mealExperimental Treatment1 Intervention
Group III: High animal protein mealExperimental Treatment1 Intervention
Group IV: Standard mealActive Control1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Missouri School of MedicineColumbia, MO
University of Missouri School of MedicineSaint Louis, MO
Washington University School of MedicineSaint Louis, MO
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Who Is Running the Clinical Trial?
University of Missouri-ColumbiaLead Sponsor
Washington University School of MedicineLead Sponsor
References
Metabolic effects of high-protein diets. [2022]Protein is more satiating than carbohydrate or fat, and high-protein diets (25%-35% of energy) are commonly used for weight loss. High-protein diets usually replace carbohydrate with protein and may be low or high in saturated fat. Invariably, serum triglyceride is lower with the lower intake of carbohydrate, but the effects on high-density lipoprotein cholesterol and low-density lipoprotein cholesterol are strongly dependent on the amount of carbohydrate restriction and the intake of saturated fat, and in some cases low-density lipoprotein cholesterol may rise despite weight loss. In situations of weight stability, higher intakes of protein are associated with lower blood pressures, and in diabetic patients higher intakes of protein are associated with lower glycosylated hemoglobin. The overall effect on long-term atherosclerosis risk is not clear, as the current limited epidemiology provides conflicting data.
The effect of high-protein diets on coronary blood flow. [2017]Recent research has demonstrated that successful simultaneous treatment of multiple risk factors including cholesterol, triglycerides, homocysteine, lipoprotein (a) [Lp(a)], fibrinogen, antioxidants, endothelial dysfunction, inflammation, infection, and dietary factors can lead to the regression of coronary artery disease and the recovery of viable myocardium. However, preliminary work revealed that a number of individuals enrolled in the original study went on popular high-protein diets in an effort to lose weight. Despite increasing numbers of individuals following high-protein diets, little or no information is currently available regarding the effect of these diets on coronary artery disease and coronary blood flow. Twenty-six people were studied for 1 year by using myocardial perfusion imaging (MPI), echocardiography (ECHO), and serial blood work to evaluate the extent of changes in regional coronary blood flow, regional wall motion abnormalities, and several independent variables known to be important in the development and progression of coronary artery disease. Treatment was based on homocysteine, Lp (a), C-reactive protein (C-RP), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and fibrinogen levels. Each variable was independently treated as previously reported. MPI and ECHO were performed at the beginning and end of the study for each individual. The 16 people (treatment group/TG) studied modified their dietary intake as instructed. Ten additional individuals elected a different dietary regimen consisting of a "high-protein" (high protein group/HPG) diet, which they believed would "improve" their overall health. Patients in the TG demonstrated a reduction in each of the independent variables studied with regression in both the extent and severity of coronary artery disease (CAD) as quantitatively measured by MPI. Recovery of viable myocardium was seen in 43.75% of myocardial segments in these patients, documented with both MPI and ECHO evaluations. Individuals in the HPG showed worsening of their independent variables. Most notably, fibrinogen, Lp (a), and C-RP increased by an average of 14%, 106%, and 61% respectively. Progression of the extent and severity of CAD was documented in each of the vascular territories with an overall cumulative progression of 39.7%. The differences between progression and extension of disease in the HPG and the regression of disease in the TG were statistically (p
Effect of dietary protein level on platelet aggregation in rat. [2019]In order to investigate the effects of dietary protein level on the development of atherosclerosis and arterial thrombosis, studies were made on platelet function, plasma lipids and aortic prostaglandin I2 biosynthesis in rats. Under the same calorie intake, the group consuming a low level of protein (10% casein) increased plasma triglycerides and platelet aggregability in comparison with control (20% casein) and high protein groups (60% casein). Moreover, the low protein group produced more thromboxane A2 and less prostaglandin I2 compared with the high protein one. These data suggest that high protein diets may have beneficial effects on arterial thrombosis.
The role of protein in weight loss and maintenance. [2023]Over the past 20 y, higher-protein diets have been touted as a successful strategy to prevent or treat obesity through improvements in body weight management. These improvements are thought to be due, in part, to modulations in energy metabolism, appetite, and energy intake. Recent evidence also supports higher-protein diets for improvements in cardiometabolic risk factors. This article provides an overview of the literature that explores the mechanisms of action after acute protein consumption and the clinical health outcomes after consumption of long-term, higher-protein diets. Several meta-analyses of shorter-term, tightly controlled feeding studies showed greater weight loss, fat mass loss, and preservation of lean mass after higher-protein energy-restriction diets than after lower-protein energy-restriction diets. Reductions in triglycerides, blood pressure, and waist circumference were also reported. In addition, a review of the acute feeding trials confirms a modest satiety effect, including greater perceived fullness and elevated satiety hormones after higher-protein meals but does not support an effect on energy intake at the next eating occasion. Although shorter-term, tightly controlled feeding studies consistently identified benefits with increased protein consumption, longer-term studies produced limited and conflicting findings; nevertheless, a recent meta-analysis showed persistent benefits of a higher-protein weight-loss diet on body weight and fat mass. Dietary compliance appears to be the primary contributor to the discrepant findings because improvements in weight management were detected in those who adhered to the prescribed higher-protein regimen, whereas those who did not adhere to the diet had no marked improvements. Collectively, these data suggest that higher-protein diets that contain between 1.2 and 1.6 g protein · kg-1 · d-1 and potentially include meal-specific protein quantities of at least ∼25-30 g protein/meal provide improvements in appetite, body weight management, cardiometabolic risk factors, or all of these health outcomes; however, further strategies to increase dietary compliance with long-term dietary interventions are warranted.
The influence of diet on the appearance of new lesions in human coronary arteries. [2016]The Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled trial of blood lipid lowering, demonstrated significant benefit in 2-year coronary angiograms. Using angiograms of subjects in the Cholesterol Lowering Atherosclerosis Study who received a placebo and 24-hour dietary recall data, we performed an epidemiologic study of risk factors for formation of new atherosclerotic lesions. Age and baseline plus on-trial lipid levels, blood pressure levels, and diet variables were included. Significant dietary energy sources were protein, carbohydrate, alcohol, total fat, and polyunsaturated fat. Each quartile of increased consumption of total fat and polyunsaturated fat was associated with a significant increase in risk of new lesions. Increased intake of lauric, oleic, and linoleic acids significantly increased risk. Subjects in the Cholesterol Lowering Atherosclerosis Study in whom new lesions did not develop increased dietary protein to compensate for reduced intake of fat by substituting low-fat meats and dairy products for high-fat meats and dairy products. These results indicate that when total and saturated fat intakes are reduced to levels recommended by the National Cholesterol Education Program, protein and carbohydrate are preferred substitutes for fat calories, rather than monounsaturated or polyunsaturated fat.
The effects of protein intake on blood pressure and cardiovascular disease. [2019]Investigators, especially those from western countries, have commonly assumed that there is either no association or a direct association of protein intake with elevated blood pressure and atherosclerosis. In contrast, recent observational studies and clinical trials have suggested that increased protein intake, particularly protein from plant sources, might actually reduce blood pressure and prevent cardiovascular disease.
High protein diets decrease total and abdominal fat and improve CVD risk profile in overweight and obese men and women with elevated triacylglycerol. [2015]It is unclear whether high protein weight loss diets have beneficial effects on weight loss, abdominal fat mass, lipids, glucose and insulin compared to conventional low fat diets in subjects at increased risk of cardiovascular disease (CVD) because of elevated glucose and triglyceride concentrations. Our objective was to determine the effects of high protein (HP) compared to standard protein (SP) diets on CVD risk in obese adults.
Associations of dietary protein with disease and mortality in a prospective study of postmenopausal women. [2023]Some weight loss diets promote protein intake; however, the association of protein with disease is unclear. In 1986, 29,017 postmenopausal Iowa women without cancer, coronary heart disease (CHD), or diabetes were followed prospectively for 15 years for cancer incidence and mortality from CHD, cancer, and all causes. Mailed questionnaires assessed dietary, lifestyle, and medical information. Nutrient density models estimated risk ratios from a simulated substitution of total and type of dietary protein for carbohydrate and of vegetable for animal protein. The authors identified 4,843 new cancers, 739 CHD deaths, 1,676 cancer deaths, and 3,978 total deaths. Among women in the highest intake quintile, CHD mortality decreased by 30% from an isoenergetic substitution of vegetable protein for carbohydrate (95% confidence interval (CI): 0.49, 0.99) and of vegetable for animal protein (95% CI: 0.51, 0.98), following multivariable adjustment. Although no association was observed with any outcome when animal protein was substituted for carbohydrate, CHD mortality was associated with red meats (risk ratio = 1.44, 95% CI: 1.06, 1.94) and dairy products (risk ratio = 1.41, 95% CI: 1.07, 1.86) when substituted for servings per 1,000 kcal (4.2 MJ) of carbohydrate foods. Long-term adherence to high-protein diets, without discrimination toward protein source, may have potentially adverse health consequences.
Prophylactic trials for stroke in stroke-prone SHR. (3) Amino acid analysis of various diets and their prophylactic effect. [2023]This study confirmed again that high protein diet feeding decreased the incidence of stroke, and high fish protein diet did attenuate severe hypertension but high soybean protein diet did not affect the hypertension. Dietary amino acid analyses indicated that increases in total amino acids, essential amino acids and nonpolar amino acids but not acid or basic amino acids were significantly related to the reduction of stroke incidence. Among essential amino acids, lysine, threonine, isoleucine, and leucine contents were inversely related to stroke incidence, and methionine content was significantly related to the dietary antihypertensive effect of high protein diets. The prophylactic effect of high protein diets may be ascribed to some amino acid constituent.
Adverse Effects Associated with Protein Intake above the Recommended Dietary Allowance for Adults. [2021]Background. While high-protein consumption-above the current recommended dietary allowance for adults (RDA: 0.8 g protein/kg body weight/day)-is increasing in popularity, there is a lack of data on its potential adverse effects. Objective. To determine the potential disease risks due to high protein/high meat intake obtained from diet and/or nutritional supplements in humans. Design. Review. Subjects. Healthy adult male and female subjects. Method. In order to identify relevant studies, the electronic databases, Medline and Google Scholar, were searched using the terms:"high protein diet," "protein overconsumption," "protein overuse," and "high meat diet." Papers not in English were excluded. Further studies were identified by citations in retrieved papers. Results. 32 studies (21 experimental human studies and 11 reviews) were identified. The adverse effects associated with long-term high protein/high meat intake in humans were (a) disorders of bone and calcium homeostasis, (b) disorders of renal function, (c) increased cancer risk, (d) disorders of liver function, and (e) precipitated progression of coronary artery disease. Conclusions. The findings of the present study suggest that there is currently no reasonable scientific basis in the literature to recommend protein consumption above the current RDA (high protein diet) for healthy adults due to its potential disease risks. Further research needs to be carried out in this area, including large randomized controlled trials.
[The effects of some nonpolar aminoacids--valine, leucine--administration on the arterial wall already exposed to a hypercholesterolemic diet]. [2015]Hypercholesterolemia plays an important role in atherosclerosis. The dietary supplementation of proteins or specific aminoacids seems to enhance the immune status in animals and humans with a complex pathological status, decreasing morbidity and mortality.
Dietary-atherosclerosis study on deceased persons. Relation of selected dietary components to raised coronary lesions. [2022]Dietary histories for 253 deceased New Orleans men were obtained retrospectively by interviewing respondents who had shared the household with these men for an average of eighteen years. Each respondent answered a detailed questionnaire designed to elicit the usual twenty-eight-day pattern of food intake of the subject during the terminal year of his life. This information was then used to calculate the average daily intake of selected dietary components. The cases included in the dietary studies were a sub-sample of cases in the International Atherosclerosis Project and were also studied for cigarette smoking habits. Analyses were performed to determine possible associations of nutrient intakes during the terminal year of life with the extent of raised lesion involvement in the three main coronary arteries measured at autopsy. These analyses indicated that higher intakes of protein of vegetal origin, total carbohydrate, starch, and crude fiber are associated with less atherosclerotic lesion involvement. For other components (total calories, total protein, animal protein, total fat, animal or vegetal fat, saturated or unsaturated fatty acids, total sugars, and cholesterol), there were no indications that the daily consumption was related to atherosclerotic lesions found at autopsy. When the diet-lesion relationships were examined on the basis of nutrient-to-calorie ratios, starch and vegetal protein were associated with less atherosclerotic lesion involvement in the coronaries, while animal protein and fat, regardless of source, were associated with greater atherosclerotic lesion involvement. These results suggest that, in general, the consumption of more foods of vegetal origin may be related to a lesser degree of atherosclerotic involvement.
[Göttingen miniature swine as a model for diet-induced atherosclerosis]. [2019]Twenty-four Göttingen Miniature Swine/csk, in order to evaluate their potential usefulness as a model for experimental atherosclerosis studies, were fed diets of three types, a high-fat plus high cholesterol diet, a high-fat diet, and a commercial diet. Each group consisted of 4 males and 4 females. Swine fed the experimental diet were investigated by gross, microscopic and serum biochemical examination on the 1st, 3rd, 6th and 9th month after start of experimentation. Lesions of atherosclerosis were observed in the high-fat plus high-cholesterol diet group. After a month on the experimental diet, intimal thickening was detected in the abdominal aorta just above the origin of internal iliac artery, left coronary artery and ascending aorta by microscopic examination. Thereafter, on the 9th month after the start, there was more extensive and severe atherosclerosis. These lesions were classified into two types by the difference in the histologic architecture of arterial wall. One was fatty streaks that were in thoracic aorta belonging to the elastic type and the other was fibrous plaques that were in abdominal aorta and iliac artery and so on, belong to the transitional or muscular type. High-fat plus high-cholesterol diet feeding led to elevated serum cholesterol and beta-lipoprotein levels, and had an effect on several kinds of metabolism. All of the swine fed high-fat or commercial diet had little gross, microscopic lesions and had no change in serum cholesterol and beta-lipoprotein levels. Hypercholesterolemia and hyper-beta-lipoproteinemia had a close relation to the development and acceleration of atherosclerosis. It was possible to show that the diet induced atherosclerosis was similar in quality to that observed in humans, and that the Göttingen miniature swine was a suitable animal for the study of atherosclerosis.
[Functional meat food in atherosclerosis prevention]. [2006]Diet is effective method of atherosclerosis prevention. Traditional meet food consists the high cholesterol level. It was shown that cholesterol level is considerable low in new functional meet food. Such food-stuff may be use for the atherosclerosis prevention.
Diet and atherogenesis. [2019]Diet is probably correlated with the prevalence of atherosclerosis in the more prosperous countries of the world. Attempts to discover the responsible items of diet would be facilitated if systematic, statistical comparisons were made between the diets in some high and low risk areas. A particular area which might lend itself for this survey is the block of five countries consisting of Austria, Czechoslovakia, Hungary, Poland and Romania. The first three of these constitute a high risk area, with mortality from ischemic heart disease of the order of 250 per year per 100,000 population, the last two a low risk area with mortality of the order of 75. Many relevant conditions, like standard of living, expectation of life, climate, etc. are reasonably similar in the five countries. Items of diet, the consumption of which is consistently higher in the high risk than in the low risk countries could constitute a short list of suspected atherogens.