Hypertension, affecting over 1 billion adults globally, is a major public health concern. Dietary intervention is a crucial non-pharmacological approach to its prevention and management. Global consensus, aligned with WHO recommendations, emphasizes a healthy diet rich in plant-based foods and low in saturated fats and sugars. Metabolomics offers valuable insights into the metabolic pathways linking nutrition and disease. Inadequate plant protein (whole grains, legumes, nuts, seeds) consumption and excessive animal protein intake (red and processed meat) contribute to increased cardiovascular risk, especially in Sub-Saharan Africa where low consumption of fruits, vegetables, and whole grains coupled with high sodium intake are leading dietary risk factors for cardiovascular disease (CVD). While discrepancies exist, high-quality plant-based diets are often associated with lower BP and CVD mortality risk, whereas higher animal protein intake is linked to increased hypertension and CVD mortality risk. These contrasting effects may be due to differences in amino acid (AA) composition, fat content, micronutrients, heme-iron, fiber, phytochemicals, and interactions with the gut microbiome. Animal proteins are richer in essential amino acids (EAAs), including branched-chain amino acids (BCAAs) and aromatic amino acids, while plant proteins are richer in nonessential AAs. Elevated BCAAs and their acylcarnitine byproducts, along with lower levels of certain nonessential AAs like glycine, serine, and histidine, have been associated with higher BP and hypertension risk. This study aimed to determine if plant and animal protein intake differentially relate to non-protein components (fiber, saturated fat, salt) or metabolomic profiles associated with BP. The hypothesis was that individuals with low animal and high plant protein intake (low-risk group) would differ significantly from those with high animal and low plant protein intake (high-risk group) in BP, body composition, non-protein components, and metabolomic profiles.

Existing research highlights the contrasting effects of plant and animal protein on blood pressure and cardiovascular health. Studies have shown that diets rich in plant-based proteins are associated with lower blood pressure and reduced risk of cardiovascular diseases. Conversely, high consumption of animal protein, particularly red and processed meats, is linked to increased blood pressure and a higher risk of cardiovascular events. These differences are believed to be due to variations in the amino acid profile, fat content, micronutrient composition, fiber, and other bioactive compounds found in plant and animal sources. Previous metabolomic studies have identified specific amino acids and metabolites associated with blood pressure regulation, providing further evidence for the role of diet in cardiovascular health. However, further research is needed to confirm these findings and to identify consistent biomarkers that can be used to support dietary assessment.

The African Prospective study on the Early Detection and Identification of CVD and Hypertension (African-PREDICT) provided data for this study. 1008 young adults (20-30 years) from the Potchefstroom area in South Africa were included, with equal sex and racial distribution. Inclusion criteria included BP < 140/90 mmHg, no self-reported chronic diseases, and HIV-uninfected status. Data collection included validated questionnaires for demographics, socioeconomic status (SES), and dietary intake (three 24-h dietary recalls). Anthropometric measurements (weight, height, waist circumference) were taken, and physical activity was assessed using accelerometers. 24-h ambulatory blood pressure monitoring was performed using the Card(X)plore device. Spot urine and blood samples were collected for metabolomic analysis (amino acids and acylcarnitines using LC-MS/MS) and biochemical analyses (serum cholesterol, GGT, CRP, HbA1c). Participants were stratified into low-risk (low animal, high plant protein) and high-risk (high animal, low plant protein) groups based on tertiles of plant and animal protein intake within sex and racial subgroups. Statistical analyses included independent t-tests and Mann-Whitney U tests for comparisons between groups, ANCOVA for adjusting for confounders, Spearman correlations, multiple linear regression, and mediation analyses. The Benjamini-Hochberg procedure adjusted p-values to control for false discovery rate.

The study cohort had an average age of 24 years. The high-risk group (high animal, low plant protein) had significantly higher 24-h SBP (p=0.011) but not diastolic BP (DBP) compared to the low-risk group. This difference became non-significant after adjusting for BMI, LDL-C, potassium excretion, Na+/K+ ratio, or saturated fat intake. Total, plant, and animal protein intakes correlated positively with SBP, but these relationships were not significant in multiple regression analyses adjusted for several confounders. In the total cohort, male sex, BMI, and saturated fat intake were significant positive predictors of 24-h SBP. Mediation analysis showed that the relationship between animal and plant protein intake and SBP was partially mediated by BMI and saturated fat. In the low-risk group, several amino acids (methionine, glutamic acid, glycine, proline) and beta-alanine showed inverse relationships with SBP and/or DBP. The high-risk group showed higher BMI, waist circumference, total cholesterol, LDL-C, GGT, CRP, total fat, saturated fat, and monounsaturated fat intake compared to the low-risk group; however, after adjustment for confounders, many of these differences became non-significant. The low-risk group had significantly higher potassium intake and fiber intake.

The findings suggest that the association between dietary protein intake and blood pressure is complex and may be influenced by other dietary factors and body composition. While an initial analysis showed a higher SBP in the high animal/low plant protein group, this effect was attenuated after adjusting for confounders such as BMI and saturated fat intake. This indicates that the observed differences in SBP might be indirectly related to dietary protein intake through its influence on BMI and fat consumption, rather than a direct effect of protein itself. The inverse relationship between certain amino acids (methionine, glutamic acid, glycine, proline, beta-alanine) and BP in the low-risk group supports the potential benefits of a diet rich in plant-based protein sources. These amino acids may contribute to improved BP control through various mechanisms. Future research could explore the specific metabolic pathways involved and investigate the potential of these amino acids as biomarkers for cardiovascular health.

This study provides evidence that the relationship between dietary protein intake and blood pressure is complex and likely influenced by mediating factors such as BMI and saturated fat intake. Higher consumption of animal protein relative to plant protein may indirectly contribute to higher SBP through increased BMI and saturated fat intake. The inverse associations of several amino acids with BP in the low-risk group highlight the potential benefits of a diet rich in plant proteins. Future studies should investigate the mediating role of the gut microbiome and explore potential interventions targeting the identified metabolic pathways to improve blood pressure control.

This study is observational and cannot establish causality. The reliance on self-reported dietary data may introduce some degree of measurement error. The study population was relatively young and homogenous, limiting the generalizability of the findings to other age groups and populations. The cross-sectional nature limits the ability to infer temporal relationships between dietary intake, metabolite levels, and BP. Furthermore, the study only assessed spot urine samples and may not fully represent the overall metabolic profile.