Abstract
Introduction
Hypertension (HTN) is a major global health burden. While dietary protein is a known modifiable risk factor, the role of specific amino acids remains controversial. This systematic review and meta-analysis investigates the association between dietary amino acid intake and the risk of hypertension.
Methods
Three electronic databases (PubMed, Scopus, Web of Science) were systematically searched from inception until September 30, 2025 for observational studies examining dietary amino acid intake and hypertension. Data extraction and quality assessment were performed. Where applicable, meta-analyses were conducted using a fixed-effect model to pool effect estimates.
Results
The sixteen included studies, with a total of 57,913 participants, comprised eight prospective cohorts, five cross-sectional studies, and three that utilized other designs. The meta-analysis of adjusted odds ratios (ORs) showed that higher intake of branched-chain, aromatic, and alcoholic amino acids was associated with a significantly increased risk of hypertension, with pooled ORs of 1.37 (95% CI: 1.14–1.66), 1.50 (95% CI: 1.22–1.85), and 1.66 (95% CI: 1.31–2.11) for the second, third, and fourth quartiles, respectively. Prospectively, higher intake of branched-chain amino acids significantly increased the hazard of hypertension. Conversely, glycine intake was consistently associated with a protective effect (pooled OR = 0.75; 95% CI: 0.64–0.89).
Conclusion
Specific dietary amino acids have distinct associations with HTN risk. Branched-chain and aromatic amino acids are associated with increased risk, while glycine demonstrates a protective effect. These findings highlight the potential for specific dietary recommendations but are limited by methodological heterogeneity across studies. Future research with standardized methodologies is needed to confirm these associations and inform clinical and public health guidance.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12889-025-25411-3.
Keywords: Dietary Amino Acid, Risk of Hypertension, Blood Pressure, Systematic Review
Introduction
Hypertension (HTN) is one of the most important health problems worldwide. It is a cause of chronic diseases such as cardiovascular disease (CVD), stroke, chronic kidney disease (CKD), and diabetes mellitus [1, 2]. An estimated 1.4 billion adults aged 30–79 years have high blood pressure in 2024 [3]. The number of deaths due to high blood pressure was 1.16 million in 2019 and is expected to rise to 1.57 million per year by 2034 [4]. Furthermore, a recent study has shown that the prevalence of HTN is decreasing in high-income countries, while it is increasing in low-income countries [4].
Multiple factors, such as age, gender, smoking, low physical activity, and unhealthy diet, are risk factors for HTN [5]. Diet, particularly protein intake, is one of the risk factors studied. According to various studies, several bodily functions, including protein synthesis, glucose metabolism, regulation of key metabolic pathways, and production of neurotransmitters in the brain such as serotonin, depend on proteins [2, 6–9]. In addition, excessive intake of certain amino acids, such as branched-chain amino acids (BCAA), may be associated with chronic diseases such as liver failure, pulmonary hypertension, insulin resistance, and consequently, obesity and type 2 diabetes [7, 8, 10–13]. Even minor nutrients can have significant effects; for example, a 2 mmHg reduction in mean blood pressure can reduce mortality from stroke by 6% and from coronary heart disease by 4% [14–16]. These cases make us aware of the importance of consuming adequate amounts of proteins and amino acids, as well as understanding their benefits and harms.
Recently, numerous studies have examined the association between amino acids and blood pressure, resulting in contradictory findings [2, 7, 11, 17, 18]. Extensive research in this area has reported positive associations in some studies, negative associations in others, and no association in others. Given the controversial results and the significance of the topic, a more comprehensive review is needed to provide stronger evidence. Therefore, this study was conducted to investigate the association between dietary amino acid intake and hypertension.
Method
Search strategy
This meta-analysis was conducted according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) [19]. Three electronic databases— PubMed, Scopus, and Web of Science—were searched to identify medical literature published from the inception of each database until September 30, 2025. To ensure comprehensive coverage, a combination of free-text terms and Medical Subject Headings (MeSH) was used, focusing on the keywords “hypertension”, “high blood pressure”, “elevated blood pressure”, “hypertensive disorder”, “HTN”, “dietary amino acid”, and “amino acid intake”. The PECO framework for this study was as follows:
Population
Individuals with varying dietary amino acid intake.
Exposure
Dietary amino acids (tryptophan, threonine, isoleucine, leucine, lysine, methionine, cysteine, phenylalanine, tyrosine, valine, arginine, histidine, alanine, aspartic acid, glutamic acid, glycine, proline, and serine).
Comparison
Different levels of dietary amino acid intake.
Outcome
Risk of hypertension
The search was limited to studies published in English. To complement the search process, a manual check of the reference lists of relevant articles and review articles was performed to identify additional publications that may have been missed in the initial search.
Study selection
The titles and abstracts of the publications were systematically screened, and all potentially relevant publications were independently reviewed using EndNote X8 software. Qualified studies were then selected for full-text screening. Any discrepancies were resolved through discussion between the two authors and re-examination of the original papers. If discrepancies could not be resolved by discussion, they were referred to the third author. Eligible studies were observational (including cohort, cross-sectional, and case–control designs) that investigated the association between dietary intake of any amino acid and hypertension or blood pressure levels in human adults or adolescents. We placed no restrictions on participant characteristics, study duration, or setting. Studies were excluded if they were not original research (e.g., reviews, editorials), did not provide a quantitative measure of association, or presented duplicate data from the same studies.
Data extraction
Two investigators extracted data from each eligible study, including the first author’s name, publication date, country of origin, study design, study population, age, sample size, types of amino acid, assessment of amino acid, amino acid category (tertile, quartile, etc.), the hypertension criteria, the mean or median systolic and diastolic blood pressure, the adjustment for confounding factors, the amino acid unit, the incidence or prevalence of hypertension and the effect measures such as odds ratio (OR), hazard ratio (HR), regression coefficients, mean differences and 95% confidence interval (CI). Another investigator checked the accuracy of the extracted data, and they were compared using a custom, piloted spreadsheet for each feature of interest.
Quality assessment
The Newcastle–Ottawa Scale (NOS) for Observational Studies was used to assess the quality of the non-randomized studies for potential risk of bias. This tool evaluates studies based on three key domains: (1) selection of the study groups, (2) comparability of the groups, and (3) ascertainment of either the outcome or exposure. A 'star system' is used to award points, with a higher score indicating a lower risk of bias. The quality of each study was categorized as good (7–9 stars), fair (5–6 stars), or poor (0–4 stars) for the purpose of sensitivity analysis [20].
Statistical analysis
The results of the included studies were first summarized in Tables 1, 2, 3 and 4, which present key characteristics, participant demographics, exposure, and adjusted outcome measures. For hypertension risk, a meta-analysis was conducted to pool adjusted ORs using the inverse-variance method. Subgroup analyses were performed based on the categorization of amino acid intake (e.g., second, third, fourth, and fifth quintiles or third tertile, as reported in the original studies). The fixed-effect model was used to aggregate data from the studies and produce pooled estimates. This model was chosen not only due to low heterogeneity but also to account for shared populations or similar designs in some included studies, further supporting the assumption of a common underlying effect. The results were presented as forest plots, with descriptions of the results in the plots, and point estimates with their 95% confidence intervals were calculated accordingly. Tests for publication bias (funnel plots and statistical tests) were not performed due to the limited number of studies (< 10) in each meta-analysis. Analyses were performed using R software, version 4.5.1.
Table 1.
The description of eligible studies reporting the association between dietary amino acids and hypertension, including crude and adjusted beta coefficients
| ID | Author, Year/Country/Study Type | Mean, Median of Age/Sample Size (n)/ Male (n, %) |
Amino acid categories | Type of amino acid | Amino acid level | n amino acid group | Mean ± SD/median (IQR) amino acid group | Unit | Mean ± SD/Median (IQR) Systolic BP | Mean ± SD/Median (IQR) Diastolic BP | Adjustment for Confounder | Crude β (95% CI) | Adjusted β (95% CI) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | de Moraes, A. C., 2015 [21]/Europe: Greece, Germany, Belgium, France, Hungary, Italy, Sweden, Austria, Spain/Cross-sectional | girl:14.7 (CI: 95% = 14.6; 14.8) boy:14.8 (CI: 95% = 14.7; 14.9)/1605/772 (in adolescents) | Aliphatic side chains | Alanine | - | - | - | gr/day |
GIRL 117.2 (116.3; 118.1) BOY 126.7 (125.5; 127.8) |
GIRL 69.1 (68.4; 69.8) BOY 68.0 (67.3; 68.8) |
City, seasonality, socioeconomic status, parental education, age (years), age at menarche, body mass index, waist circumference, physical activity, tobacco smoking, total energy and sodium intake |
GIRL DBP: −0.01 (−0.06; 0.03) SBP:0.02 (−0.05; 0.08) BOY DBP:0.01 (−0.04; 0.06) SBP:0.02 (−0.05; 0.09) |
GIRL DBP:−1.41(−2.78; −0.39) SBP: −0.70 (−2.67; 1.27) BOY DBP:0.72 (−1.46; 2.90) SBP:1.89 (−0.37; 4.16) |
| Glycine |
GIRL 3.64 (3.56; 3.72) BOY 3.69 (3.59; 3.78) |
GIRL BP: −0.01 (−0.07; 0.05) BP:0.02 (−0.06; 0.10) BOY BP:0.02 (−0.04; 0.07) SBP:0.02 (−0.06; 0.10) |
GIRL DBP:0.07 (−0.67; 0.82) SBP: −0.58 (−1.55; 0.41) BOY DBP: −0.35 (−1.85; 1.14) SBP: −1.04 (−2.41; 0.35) |
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| Isoleucine |
GIRL 4.29 (4.19; 4.38) BOY 4.33 (4.22; 4.44) |
GIRL DBP:−0.02 (- 0.07; 0.03) SBP:0.02 (−0.05; 0.09) BOY DBP:0.02 (−0.03; 0.06) SBP:0.02 (−0.05; 0.09) |
GIRL DBP: −0.39 (−1.80; 1.02) SBP: −0.67 (−2.53; 1.20) BOY DBP: −0.90 (−3.32; 1.53) SBP: −0.07 (−2.45; 2.32) |
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| Leucine |
GIRL 6.71 (6.81; 7.12) OY 7.05 (6.87; 7.22) |
GIRL DBP: −0.01 (−0.04; 0.02) SBP:0.01 (−0.03; 0.06) BOY DBP:0.01 (−0.02; 0.04) SBP:0.01 (−0.03; 0.06) |
GIRL DBP:0.72 (−0.50; 1.94) BP:0.15 (−1.54; 1.84) BOY DBP:0.19 (−1.77; 2.15) BP: −0.35 (−2.37; 1.67) |
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| Valine |
GIRL 4.85 (4.75; 4.95) BOY 4.91 (4.79; 5.03) |
GIRL DBP: −0.02 (−0.06; 0.03) SBP:0.02 (−0.04; 0.08) BOY DBP:0.02 (−0.03; 0.06) SBP:0.02 (−0.04; 0.08) |
GIRL DBP: −0.40 (−1.84; 1.04) SBP: −0.61 (−2.61; 1.39) BOY DBP: −1.51 (−4.17; 1.14) SBP: −1.56 (−3.79; 0.67 |
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| Aromatic side chains | Phenylalanine |
GIRL 3.96 (3.88; 4.05) BOY 4.01 (3.92; 4.11) |
GIRL DBP: −0.02 (−0.07; 0.03) SBP:0.03 (−0.05; 0.11) BOY DBP:0.02 (−0.03; 0.08) SBP:0.03 (−0.05; 0.11) |
GIRL BP:0.27 (−1.44; 1.99) SBP: −1.69 (−4.15; 0.78) BOY DBP:2.09 (−0.73; 3.49) SBP:0.02 (−2.33; 2.38) |
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| Tryptophan |
GIRL 3.54 (3.17; 3.62) BOY 3.58 (3.49; 3.67) |
GIRL DBP: −0.05 (−0.27; 0.16) BP:0.10 (−0.20; 0.40) BOY DBP:0.08 (−0.13; 0.29) SBP:0.10 (−0.20; 0.40) |
GIRL DBP:2.80 (−1.27; 6.86) SBP:4.41 (0.11; 9.96) BOY DBP:2.52 (−4.96; 10.00) SBP:8.74 (−0.14; 16.06) |
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| Tyrosine |
GIRL 1.20 (0.99; 1.04) BOY 1.03 (1.01; 1.06) |
GIRL DBP: −0.03 (−0.09; 0.04) BP:0.03 (−0.07; 0.12) BOY DBP:0.03 (−0.04; 0.09) SBP:0.03 (−0.07; 0.12) |
GIRL DBP: −2.68 (−4.46; −0.90) SBP: −2.14 (−4.43; −0.01) BOY DBP: −0.23 (−3.12; 2.65) BP: −0.51 (−3.35; 2.38) |
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| Basic side chains | Arginine |
GIRL 4.86 (4.76; 4.97) BOY 4.93 (4.79; 5.05) |
GIRL DBP: −0.01 (−0.05; 0.03) BP:0.02 (−0.04; 0.08) BOY DBP:0.02 (−0.03; 0.06) SBP:0.02 (−0.04; 0.08) |
GIRL DBP:0.45 (−0.08; 0.98) SBP:0.51 (−0.18; 1.20) BOY DBP:0.26 (−0.79; 1.30) SBP:1.01 (−0.08; 1.94) |
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| Histidine |
GIRL 2.23 (2.38; 2.48) BOY 2.45 (2.39; 2.52) |
GIRL DBP: −0.02 (−0.10; 0.07) SBP:0.03 (−0.09; 0.15) BOY DBP:0.02 (−0.06; 0.11) SBP:0.03 (−0.09; 0.15) |
GIRL DBP:0.59 (−0.39; 1.57) SBP:1.13 (0.18; 2.45) BOY DBP:0.27 (−1.44; 1.97) SBP:1.01 (0.08; 1.94) |
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| Lysine |
GIRL 5.97 (5.83; 6.10) BOY 6.03 (5.87; 7.22) |
GIRL DBP: −0.01 (−0.04; 0.03) SBP:0.08 (−0.04; 0.05) BOY DBP:0.01 (−0.03; 0.04) SBP:0.01 (−0.04; 0.05) |
GIRL DBP: −0.05 (−0.73; 0.64) SBP:0.44 (−1.40; 0.51) BOY DBP: −0.37 (−1.52; 0.77) SBP: −0.47 (−1.55; 0.60) |
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| Acidic side chains | Aspartic acid |
GIRL 7.79 (7.62; 7.96) BOY 7.89 (7.69; 8.09) |
GIRL DBP: −0.01 (−0.04; 0.02) SBP:0.01 (−0.03; 0.05) BOY DBP:0.01 (−0.02; 0.04) SBP:0.01 (−0.03; 0.05) |
GIRL DBP:0.25 (−0.05; 0.56) SBP: −0.20 (−0.61; 0.22) BOY DBP:0.18 (- 0.35; 0.70) SBP: −0.24 (−0.72; 0.24) |
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| Glutamic acid |
GIRL 17.94 (17.57; 18.32) OY 18.11 (17.68; 18.54) |
GIRL DBP: −0.01 (−0.02; 0.01) SBP:0.09 (−0.09; 0.03) BOY DBP:0.01 (−0.01; 0.04) SBP:0.01 (−0.01; 0.03) |
GIRL DBP: −0.02 (−0.20; 0.15) SBP: −0.15 (−0.39; 0.09) BOY DBP: −0.05 (−0.31; 0.21) SBP: −0.02 (−0.29; 0.25) |
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| Hydroxyl side chains | Serine |
GIRL 4.30 (4.21; 4.39) BOY 4.35 (4.25; 4.45) |
GIRL DBP: −0.02 (−0.07; 0.03) SBP:0.03 (−0.04; 0.10) BOY DBP:0.02 (−0.03; 0.07) SBP:0.03 (−0.04; 0.10) |
GIRL DBP:0.48 (−0.51; 1.48) SBP:1.11 (−0.17; 2.40) BOY DBP: −1.26 (−2.79; 0.28) SBP:0.48 (−0.99; 1.94) |
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| Threonine |
GIRL 3.17 (3.10; 3.23) BOY 3.20 (3.12; 3.28) |
GIRL DBP: −0.02 (−0.08; 0.04) SBP:0.02 (−0.06; 0.11) BOY DBP:0.02 (−0.04; 0.08) SBP:0.02 (−0.06; 0.11) |
GIRL DBP: −0.39 (−2.42; 1.63) SBP:3.18 (−0.36; 5.99) BOY DBP:1.56 (−2.30; 5.41) SBP:0.05 (−2.81; 2.91) |
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| Sulfur-containing side chains | Cysteine |
GIRL 1.19 (1.17; 1.22) BOY 1.20 (1.17; 1.23) |
GIRL DBP: −0.07 (−0.25; 0.10) SBP:0.08 (−0.17; 0.34) BOY DBP:0.05 (−0.13; 0.23) SBP:0.08 (−0.17; 0.34) |
GIRL DBP: −1.29 (−3.61; 1.03) SBP:0.60 (−2.60; 3.81) BOY DBP: −2.56 (−6.23; 1.12) SBP: −3.51 (−7.13; 0.11) |
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| Methionine |
GIRL 1.96 (1.91; 199) BOY 1.97 (1.92; 2.02) |
GIRL DBP: −0.02 (−0.13; 0.08) SBP:0.02 (−0.13; 0.17) BOY DBP:0.02 (−0.08; 0.13) SBP:0.02 (−0.13; 0.17) |
GIRL DBP:2.78 (0.98; 4.59) SBP:0.87 (−1.47; 3.21) BOY DBP: −0.785 (−3.39; 1.88) SBP: −0.84 (−3.06; 1.36) |
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| Cyclic side chain | Proline |
GIRL 6.40 (6.26; 6.54) BOY 6.47 (6.30; 6.61) |
GIRL DBP: −0.02 (−0.05; 0.01) SBP:0.03 (−0.02; 0.07) BOY DBP:0.01 (−0.02; 0.05) SBP:0.03 (−0.02; 0.07) |
GIRL DBP: −0.10 (−0.50; 0.29) SBP:0.34 (−0.18; 0.86) BOY DBP:0.31 (−0.33; 0.95) SBP:0.43 (−0.20; 1.05) |
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| 2 | Javidan, A. N., 2017 [22]/Iran/Cross-sectional | 36.25 ± 10.76/265/217(among individuals with spinal cord injury) | - | Tryptophan | - | - | 667.42 ± 262 | mg/day | - | - | Age, gender, BMI, injury completeness, plegia type, dietary intake of total energy | - |
S1, SBP:−0.23, DBP:−0.02 S2, SBP:−0.32, DBP:−0.34 |
| Isoleucine | 2900.0 ± 1119.8 |
S1, SBP:0.98, DBP:0.99 S2, SBP:1.17, DBP:1.19 |
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| Lysine | 4201.0 ± 1698.8 |
S1, SBP:0.23, DBP:0.64 S2, SBP:1.54, DBP:0.40 |
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| Cysteine | 780.57 ± 297.17 |
S1, SBP:0.11, DBP:−0.01 S2, SBP:0.55, DBP:−0.12 |
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| Tyrosine | 2103.52 ± 811.13 |
S1, SBP:−0.87, DBP:−0.68 S2, SBP:−0.99, DBP:−0.46 |
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| Arginine | 231.77 ± 186.44 |
S1, SBP:0.88, DBP:0.33 S2, SBP:0.77, DBP:0.67 |
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| Alanine | 222.39 ± 167.70 |
S1, SBP:0.42, DBP:0.23 S2, SBP:0.68, DBP:0.66 |
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| Glutamic | 935.78 ± 576.87 |
S1, SBP:0.55, DBP:0.59 S2, SBP:0.39, DBP:0.21 |
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| Threonine | 1437.5 ± 876.33 |
S1, SBP:−0.98, DBP:−0.82 S2, SBP:−1.22, DBP:−1.09 |
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| Leucine | .3325.21 ± 1974.77 |
S1, SBP:−1.02, DBP:−0.98 S2, SBP:−1.02, DBP:−0.58 |
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| Methionine | 1366.42 ± 539.50 |
S1, SBP:0.78, DBP:0.89 S2, SBP:0.23, DBP:0.40 |
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| Phenylalanine | 2693.14 ± 1017.63 |
S1, SBP:0.12, DBP:0.93 S2, SBP:0.25, DBP:0.88 |
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| Valine | 3397.94 ± 1307.63 |
S1, SBP:0.23, DBP:0.64 S2, SBP:0.20, DBP:0.76 |
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| Histidine | 1625.93 ± 658.37 |
S1, SBP:−0.79, DBP:−0.66 S2, SBP:−0.89, DBP:−1.09 |
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| Aspartic acid | 377.58 ± 154.53 |
S1, SBP:0.65, DBP:0.79 S2, SBP:0.78, DBP:1.31 |
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| 3 | Liu, Y., 2022 [26]/China/Prospective cohort |
Men: 44.4 ± 14.2 Women: 44.8 ± 13.9/8491/3995 |
Branched-chain amino acids | Isoleucine | Q1 |
men:1001 women:1132 |
men: < 1.66 women: < 1.57 |
gr/day |
Baseline men:117.3 ± 10.4 Baseline women:113.5 ± 11.9 At the end of follow up men:123.6 ± 15.4, At the end of follow up women:120.5 ± 17.0 |
Baseline men:76.3 ± 7.5 Baseline women:73.9 ± 8.1 At the end of follow up men:80.8 ± 10.5, At the end of follow up women:77.6 ± 10.5 |
Age, ethnicity, education, urban residents, diagnosed T2DM, physical activity, smoking, alcohol drinking, energy, carbohydrate, fat, protein, and salt intake | - |
(per SD increase) SBP men: 2.55 (1.84, 3.25) women: 1.82 (1.16, 2.49) DBP men:1.27 (0.78, 1.76) women: 0.97 (0.52, 1.42) |
| Q2 |
men:994 women:1119 |
men: 1.66–2.32 women:1.57–2.15 |
|||||||||||
| Q3 |
men:997 women:1128 |
men: 2.32–3.06 women: 2.15–2.87 |
|||||||||||
| Q4 |
men:1003 women:1117 |
men: ≥ 3.06 women: ≥ 2.87 |
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| Leucine | Q1 |
men:998 women:1118 |
men: < 2.94 women: < 2.76 |
SBP men: 2.39 (1.70, 3.07) women: 1.80 (1.15, 2.45) DBP men:1.21 (0.73, 1.69) women: 0.96 (0.52, 1.41) |
|||||||||
| Q2 |
men:1004 women:1127 |
men: 2.94–4.12 women: 2.76–3.82 |
|||||||||||
| Q3 |
men:997 women:1133 |
men: 4.12–5.54 women: 3.82–5.15 |
|||||||||||
| Q4 |
men:996 women:1118 |
men: ≥ 5.54 women: ≥ 5.15 |
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| Valine | Q1 |
men:999 women:1122 |
men: < 1.96 women: < 1.85 |
SBP men: 2.40 (1.71, 3.09) women: 1.74 (1.09, 2.39) DBP men:1.19 (0.70, 1.67) women: 0.92 (0.48, 1.37) |
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| Q2 |
men:1000 women:1123 |
men: 1.96–2.71 women: 1.85–2.52 |
|||||||||||
| Q3 |
men:991 women:1126 |
men: 2.71–3.61 women: 2.52–3.37 |
|||||||||||
| Q4 |
men:1005 women:1125 |
men: ≥ 3.61 omen: ≥ 3.37 |
IQR Interquartile Range, SD Standard Deviation, Q Quartile, CI Confidence Interval, S1 = Step 1, S1 = Step 2 (from Hierarchical regression analysis), SBP Systolic Blood Pressure, SBP Systolic Blood Pressure, BMI Body Mass Index, T2DM Type 2 Diabetes Mellitus
Table 2.
The description of eligible studies reporting the association between dietary amino acids and hypertension, including adjusted odds ratio
| ID | Author, Year/ Country/ Study Type |
Mean, Median of Age/ Sample Size (n)/ Male (n, %) |
Amino acid categories | Type of amino acid | Amino acid level | n amino acid group | Mean ± SD/median (IQR) amino acid group | Unit | Hypertension Criteria | Mean ± SD/Median (IQR) Systolic BP | Mean ± SD/Median (IQR) Diastolic BP | Incidence of hypertension | Adjustment for Confounder | Adjusted OR | Lower CI | Upper CI |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Katherine R. Tuttle, 2012 [23]/U.S.A/Observational cohort study by secondary analysis of clinical trial | 59 ± 9/92/70 (76%)(patients with cardiovascular disease) | Threonine | Threonine | per Q | - | - | mg/day | Joint National Committee 7 Guidelines10 or drug therapy specifically administered for hypertension | 119 ± 16 | 72 ± 10 | 44/92 | Age, gender, diabetes, alcohol use, diuretic use, BMI, ACE inhibitor, eGFR, daily protein, fruits & vegetables, dairy, urinary sodium & potassium |
SBP: 0.84 DBP: 0.87 |
SBP: 0.74 DBP: 0.75 |
SBP: 0.96 DBP: 1.01 |
| Methionine | Methionine | per Q |
SBP: 1.29 DBP: 1.21 |
SBP: 1.14 DBP: 1.05 |
SBP: 1.46 DBP: 1.39 |
|||||||||||
| Cysteine | Cysteine | per Q |
SBP: 0.96 DBP: 0.91 |
SBP: 0.88 DBP: 0.83 |
SBP: 1.06 DBP: 1.00 |
|||||||||||
| Phenylalanine | Phenylalanine | per Q |
SBP: 1.06 DBP: 1.14 |
SBP: 0.95 DBP: 1.02 |
SBP: 1.19 DBP: 1.28 |
|||||||||||
| Histidine | Histidine | per Q |
SBP: 0.92 DBP: 0.89 |
SBP: 0.86 DBP: 0.82 |
SBP: 1.00 DBP: 0.97 |
|||||||||||
| Alanine | Alanine | per Q |
SBP: 1.17 DBP: 1.22 |
SBP: 1.05 DBP: 1.07 |
SBP: 1.30 DBP: 1.38 |
|||||||||||
| Glutamate | Glutamate | per Q |
SBP: 1.13 DBP: 1.09 |
SBP: 1.00 DBP: 0.95 |
SBP: 1.28 DBP: 1.24 |
|||||||||||
| 2 | Teymoori Safa, F., 2017 [27]/Iran/Prospective cohort study | 47.1 ± 8.3/2612/42.9% males (1120) | Glycine | Glycine | T1 | 888 | median: 3.51 | gr/day | age > 60: SBP ≥ 150 OR DBP ≥ 90 age < 60 SBP ≥ 140 OR DBP ≥ 90 OR using hypertension drugs for both groups | 113.7 ± 14.7 | 76.7 ± 8.8 |
Total: 14% (365/2612) 129/888 |
Age, gender, BMI, diabetes, smoking, physical activity, energy intake, saturated and unsaturated fatty acids, fiber, calcium, sodium, potassium | Ref | ||
| T2 | 875 | median: 3.79 | 114.6 ± 14.8 | 76.9 ± 8.7 | 135/875 | 1.00 | 0.75 | 1.34 | ||||||||
| T3 | 849 | median: 4.07 | 114.5 ± 13.8 | 77.0 ± 8.6 | 101/849 | 0.69 | 0.49 | 0.96 | ||||||||
| 3 | Teymoori, F., 2017 [27]/Iran/Population-based cohort | 39.7 ± 12.8/4288/41.9% males | Aromatic amino acids | Aromatic amino acids | Q1 | 1072 |
median (IQR):7.38 (5.88–9.34) median (% from pr):8.98 |
gr/day |
age > 60: SBP ≥ 150 OR DBP ≥ 90 age < 60: SBP ≥ 140 OR DBP >= 90 OR using hypertension drugs for both groups |
109.0 ± 12.2 | 73.3 ± 8.3 | Total: 429 (10%) | Age and sex, body mass index, physical activity, smoking (yes or no), and daily energy intake, carbohydrates, fat, saturated fatty acids, polyunsaturated fatty acids, fiber, calcium, magnesium, sodium, and potassium | Ref | ||
| Q2 | 1072 | median (% from pr):9.29 | 108.9 ± 12.2 | 73 ± 8.4 | 1.61 | 1.14 | 2.28 | |||||||||
| Q3 | 1072 | median (% from pr):9.5 | 109.4 ± 12.1 | 73.1 ± 8.3 | 1.53 | 1.05 | 2.23 | |||||||||
| Q4 | 1072 | median (% from pr):9.8 | 108.6 ± 12 | 73 ± 8.7 | 1.63 | 1.06 | 2.50 | |||||||||
| Phenylalanine | Q1 | 1072 | 4.48 | - | - | Ref | ||||||||||
| Q2 | 1072 | 4.65 | - | - | 1.71 | 1.21 | 2.41 | |||||||||
| Q3 | 1072 | 4.76 | - | - | 1.38 | 0.95 | 2.01 | |||||||||
| Q4 | 1072 | 4.9 | - | - | 1.66 | 1.14 | 2.478 | |||||||||
| Tyrosine | Q1 | 1072 | 3.28 | - | - | Ref | ||||||||||
| Q2 | 1072 | 3.45 | - | - | 1.21 | 0.87 | 1.69 | |||||||||
| Q3 | 1072 | 3.6 | - | - | 1.17 | 0.8 | 1.71 | |||||||||
| Q4 | 1072 | 3.81 | - | - | 1.20 | 0.77 | 1.87 | |||||||||
| Tryptophan | Q1 | 1072 | 1.07 | - | - | Ref | ||||||||||
| Q2 | 1072 | 1.12 | - | - | 1.25 | 0.90 | 1.73 | |||||||||
| Q3 | 1072 | 1.17 | - | - | 1.07 | 0.75 | 1.53 | |||||||||
| Q4 | 1072 | 1.23 | - | - | 1.20 | 0.78 | 1.85 | |||||||||
| 4 | Teymoori, F., 2017 [27]/Iran/Prospective cohort |
39.7 ± 12.8/ 4288/ 41.9% males |
Patten 1: Branched chain, alcoholic, aromatic amino acids, and proline, and small amino acids | Branched chain, alcoholic, aromatic amino acids, and proline, and small amino acids | Q1 | 1072 | - | - |
age > 60: SBP ≥ 150 OR DBP ≥ 90 age < 60: SBP ≥ 140 OR DBP ≥ 90 OR using hypertension drugs for both groups |
108.9 ± 11.9 | 73.3 ± 8.4 | Total: 429 (10%),97/1072 | Age and sex,, body mass index, physical activity, smoking (yes or no) and daily energy intake, saturated fatty acids, poly unsaturated fatty acids, mono unsaturated fatty acids, calcium, magnesium, sodium, potassium, and fiber | Ref | ||
| Q2 | - | - | 100/1072 | 1.24 | 0.90 | 1.72 | ||||||||||
| Q3 | - | - | 115/1072 | 1.72 | 1.21 | 2.44 | ||||||||||
| Q4 | 108.9 ± 12.2 | 73.2 ± 8.6 | 117/1072 | 1.83 | 1.21 | 2.77 | ||||||||||
|
Patten 2: Acidic amino acids, proline, alkaline and small amino acids |
Acidic amino acids, proline, alkaline and small amino acids |
Q1 | 108.5 ± 11.7 | 72.9 ± 8.2 | 107/1072 | Ref | ||||||||||
| Q2 | - | - | 93/1072 | 0.91 | 0.67 | 1.25 | ||||||||||
| Q3 | - | - | 109/1072 | 1.10 | 0.81 | 1.50 | ||||||||||
| Q4 | 109.3 ± 12.2 | 73.4 ± 8.5 | 120/1072 | 1.04 | 0.74 | 1.48 | ||||||||||
| Patten 3: Sulfuric and small amino acids | Sulfuric and small amino acids | Q1 | 108.5 ± 12.5 | 73.0 ± 8.2 | 119/1072 | Ref | ||||||||||
| Q2 | - | - | 119/1072 | 1.10 | 0.81 | 1.48 | ||||||||||
| Q3 | - | - | 101/1072 | 0.90 | 0.65 | 1.25 | ||||||||||
| Q4 | 109.0 ± 11.9 | 73.4 ± 8.5 | 90/1072 | 0.81 | 0.65 | 1.16 | ||||||||||
| 5 | Teymoori, F., 2018 [18]/Iran |
39.7 ± 12.8/4287/ 41.9% males |
Leucine, serine, threonine, tryptophan | Leu.Ser/Thr.Trp | Q1 | 1071 | median: 2.51 | gr/day |
age > 60: SBP ≥ 150 OR DBP ≥ 90 age < 60: SBP ≥ 140 OR DBP ≥ 90 OR using hypertension drugs for both groups |
108.4 ± 11.9 | 73.1 ± 8.3 | 429 (10%) cases | Age and sex, diabetes (yes or no), body mass index, physical activity, smoking (yes or no) and daily energy intake, carbohydrates, saturated fatty acids, poly unsaturated fatty acids, fiber, sodium, calcium, and potassium, adjusted for baseline SBP or DBP | Ref | ||
| Q2 | 1073 | 2.6 | 109.2 ± 11.6 | 73.3 ± 8.4 | 1.14 | 0.84 | 1.56 | |||||||||
| Q3 | 1072 | 2.67 | 108.7 ± 12.0 | 73.0 ± 8.1 | 1.22 | 0.87 | 1.69 | |||||||||
| Q4 | 1071 | 2.76 | 108.9 ± 12.2 | 73.1 ± 8.7 | 1.48 | 1.04 | 2.09 | |||||||||
| Leu/Trp | Q1 | 1071 | 6.17 | - | - | Ref | ||||||||||
| Q2 | 1073 | 6.62 | - | - | 0.90 | 0.66 | 1.23 | |||||||||
| Q3 | 1072 | 7 | - | - | 1.29 | 0.94 | 1.76 | |||||||||
| Q4 | 1071 | 7.59 | - | - | 1.22 | 0.87 | 1.72 | |||||||||
| Leu/Thr | Q1 | 1071 | 2.02 | - | - | Ref | ||||||||||
| Q2 | 1073 | 2.08 | - | - | 1.20 | 0.87 | 1.64 | |||||||||
| Q3 | 1072 | 2.13 | - | - | 1.12 | 0.79 | 1.58 | |||||||||
| Q4 | 1071 | 2.19 | - | - | 1.46 | 1.01 | 2.12 | |||||||||
| Ser/Thr | Q1 | 1071 | 1.26 | - | - | Ref | ||||||||||
| Q2 | 1073 | 1.33 | - | - | 0.99 | 0.72 | 1.36 | |||||||||
| Q3 | 1072 | 1.38 | - | - | 1.17 | 0.85 | 1.61 | |||||||||
| Q4 | 1071 | 1.43 | - | - | 1.26 | 0.90 | 1.77 | |||||||||
| 6 | Mirmiran, P., 2019 [7]/Iran/Population-based prospective cohort |
39.7 ± 12.8/ 4288/ 41.9% males |
Branched chain amino acids | BCAAs | Q1 | 1072 | 17.00 (16.66–17.20) | gr/day | SBP ≥ 140 mm Hg, DBP ≥ 90 mm Hg, or taking antihypertensive medications for subjects aged < 60 years and SBP ≥ 150 mm Hg, DBP ≥ 90 mm Hg or taking antihypertensive medications for those aged ≥ 60 years | 111.7 ± 13.7 | 75.3 ± 9.0 | 429 (10%) cases | Age and sex, diabetes, body mass index, physical activity, smoking (yes or no), and daily energy intake, carbohydrates, fat, saturated fatty acids, poly unsaturated fatty acids, fiber, calcium, magnesium, sodium, and potassium (all continuous) | Ref | ||
| Q2 | 17.66 (17.53–17.81) | 111.7 ± 14.2 | 75.3 ± 8.9 | 1.33 | 0.97 | 1.82 | ||||||||||
| Q3 | 18.21 (18.07–18.35) | 111.0 ± 13.6 | 75.0 ± 8.9 | 1.29 | 0.91 | 1.84 | ||||||||||
| Q4 | 19.00 (18.73–19.44) | 111.7 ± 14.2 | 75.4 ± 9.2 | 1.54 | 1.03 | 2.32 | ||||||||||
| Valine | Valine | Q1 | 5.16 (5.07–5.25) | - | - | Ref | ||||||||||
| Q2 | 5.42 (5.37–5.47) | - | - | 1.18 | 0.86 | 1.62 | ||||||||||
| Q3 | 5.64 (5.58–5.70) | - | - | 1.43 | 1.02 | 1.99 | ||||||||||
| Q4 | 5.98 (5.86–6.16) | - | - | 1.61 | 1.10 | 2.36 | ||||||||||
| Leucine | Leucine | Q1 | 7.46 (7.30–7.55) | - | - | Ref | ||||||||||
| Q2 | 7.75 (7.69–7.81) | - | - | 1.18 | 0.85 | 1.62 | ||||||||||
| Q3 | 7.97 (7.92–8.03) | - | - | 1.39 | 0.98 | 1.97 | ||||||||||
| Q4 | 8.29 (8.19–8.48) | - | - | 1.42 | 0.94 | 2.14 | ||||||||||
| Isoleucine | Isoleucine | Q1 | 4.30 (4.22–4.35) | - | - | Ref | ||||||||||
| Q2 | 4.48 (4.44–4.51) | - | - | 1.19 | 0.86 | 1.63 | ||||||||||
| Q3 | 4.60 (4.56–4.63) | - | - | 1.11 | 0.77 | 1.59 | ||||||||||
| Q4 | 4.76 (4.71–4.85) | - | - | 1.07 | 0.69 | 1.66 | ||||||||||
| 7 |
Najafi, F., 2024 [28]/ Iran/ Nested case–control |
-/ 2455 (491 case, 1964 control)/ - |
Branched-chain amino acids | Leucine | T1 | 491 case, 1964 control | median: 3.21 (2.05) in case, 3.35 (2.13) in control | gr/day |
Systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg and/or current use of antihypertensive medication among subjects who were free of illness at the start of the cohort study |
- | - | 491 case | Residency (urban, rural), education, SES (poor, moderate and high), BMI, WHtR, smoking (non-smoker/passive smoker, current/former smoker), and daily energy intake, physical activity (METs) (low, moderate and high), family history of hypertension, dietary patterns (healthy or unhealthy), and comorbidities (yes or no) | Ref | ||
| T2 | 1.09 | 0.81 | 1.43 | |||||||||||||
| T3 | 1.16 | 0.79 | 1.70 | |||||||||||||
| Isoleucine | T1 | median: 1.95 (1.24) in case, 2.0 (2.13) in control | Ref | |||||||||||||
| T2 | 1.04 | 0.78 | 1.38 | |||||||||||||
| T3 | 1.10 | 0.76 | 1.60 | |||||||||||||
| Valine | T1 | median: 2.29 (1.43) in case, 2.37 (1.49) in control | Ref | |||||||||||||
| T2 | 0.97 | 0.73 | 1.30 | |||||||||||||
| T3 | 1.05 | 0.71 | 1.53 | |||||||||||||
| Aromatic amino acids | Tryptophan | T1 | median: 0.48 (0.29) in case, 0.49 (0.31) in control | Ref | ||||||||||||
| T2 | 1.10 | 0.83 | 1.47 | |||||||||||||
| T3 | 0.97 | 0.65 | 1.43 | |||||||||||||
| Phenylalanine | T1 | median: 1.92 (1.19) in case, 1.94 (1.20) in control | Ref | |||||||||||||
| T2 | 1.09 | 0.82 | 1.45 | |||||||||||||
| T3 | 1.10 | 0.75 | 1.62 | |||||||||||||
| Tyrosine | T1 |
median: 1.43 (0.88) in case, 1.46 (0.94 ) in control |
Ref | |||||||||||||
| T2 | 1.01 | 0.76 | 1.34 | |||||||||||||
| T3 | 1.06 | 0.73 | 1.55 | |||||||||||||
| Alkaline | Histidine | T1 | median: 1.12 (0.73) in case, 1.15 (0.76) in control | Ref | ||||||||||||
| T2 | 0.99 | 0.74 | 1.31 | |||||||||||||
| T3 | 1.02 | 0.70 | 1.49 | |||||||||||||
| Arginine | T1 | median: 2.55 (1.64) in case, 2.64 (1.73) in control | Ref | |||||||||||||
| T2 | 1.09 | 0.81 | 1.45 | |||||||||||||
| T3 | 1.08 | 0.73 | 1.60 | |||||||||||||
| Lysine | T1 | median: 2.84 (1.95) in case, 2.88 (1.98) in control | Ref | |||||||||||||
| T2 | 0.99 | 0.74 | 1.31 | |||||||||||||
| T3 | 1.04 | 0.71 | 1.50 | |||||||||||||
| Sulfuric | Methionine | T1 | median: 0.93 (0.63) in case, 0.95 (0.63) in control | Ref | ||||||||||||
| T2 | 1.12 | 0.85 | 1.47 | |||||||||||||
| T3 | 1.06 | 0.74 | 1.53 | |||||||||||||
| Cysteine | T1 | median: 0.60 (0.35) in case, 0.60 (0.37) in control | Ref | |||||||||||||
| T2 | 1.17 | 0.88 | 1.55 | |||||||||||||
| T3 | 1.17 | 0.79 | 1.74 | |||||||||||||
| Acidic | Glutamic Acid | T1 | median: 8.23 (4.67) in case, 8.25 (4.90) in control | Ref | ||||||||||||
| T2 | 0.95 | 0.71 | 1.27 | |||||||||||||
| T3 | 1.01 | 0.68 | 1.50 | |||||||||||||
| Aspartic Acid | T1 | median: 4.45 (2.73) in case, 4.53 (2.88) in control | Ref | |||||||||||||
| T2 | 1.05 | 0.78 | 1.41 | |||||||||||||
| T3 | 1.12 | 0.74 | 1.69 | |||||||||||||
| Alcoholic | Serine | T1 | median: 1.98 (1.22) in case, 2.04 (1.25) in control | Ref | ||||||||||||
| T2 | 0.89 | 0.66 | 1.18 | |||||||||||||
| T3 | 1.08 | 0.71 | 1.58 | |||||||||||||
| Threonine | T1 | median: 1.67 (1.06) in case, 1.71 (1.12) in control | Ref | |||||||||||||
| T2 | 1.05 | 0.79 | 1.40 | |||||||||||||
| T3 | 1.06 | 0.73 | 1.56 | |||||||||||||
| Small amino acids | Glycine | T1 | median: 1.71 (1.17) in case, 1.76 (1.19) in control | Ref | ||||||||||||
| T2 | 1.07 | 0.81 | 1.42 | |||||||||||||
| T3 | 1.03 | 0.71 | 1.50 | |||||||||||||
| Alanine | T1 | median: 2.12 (1.42) in case, 2.18 (1.43) in control | Ref | |||||||||||||
| T2 | 1.01 | 0.76 | 1.35 | |||||||||||||
| T3 | 1.06 | 0.72 | 1.56 | |||||||||||||
| Cyclic side chains | Proline | T1 | median: 2.41 (1.43) in case, 2.39 (1.54) in control | Ref | ||||||||||||
| T2 | 0.97 | 0.72 | 1.28 | |||||||||||||
| T3 | 1.04 | 0.71 | 1.53 | |||||||||||||
| Branched-chain | Leucine, Isoleucine, Valine | T1 | median: 7.48 (4.70) in case, 7.74 (4.98) in control | Ref | ||||||||||||
| T2 | 1.11 | 0.83 | 1.47 | |||||||||||||
| T3 | 1.20 | 0.81 | 1.73 | |||||||||||||
| Aromatic | Tryptophan, Phenylalanine, Tyrosine | T1 | median: 3.84 (2.37) in case, 3.93 (2.47) in control | Ref | ||||||||||||
| T2 | 1.08 | 0.81 | 1.43 | |||||||||||||
| T3 | 1.14 | 0.78 | 1.67 | |||||||||||||
| Alkaline | Histidine, Arginine, Lysine | T1 | median: 6.54 (4.21) in case, 6.71 (4.50) in control | Ref | ||||||||||||
| T2 | 1.04 | 0.78 | 1.38 | |||||||||||||
| T3 | 1.07 | 0.73 | 1.58 | |||||||||||||
| Sulfuric | Methionine, Cysteine | T1 | median: 1.55 (0.97) in case, 1.57 (1.00) in control | Ref | ||||||||||||
| T2 | 1.15 | 0.87 | 1.52 | |||||||||||||
| T3 | 1.10 | 0.75 | 1.61 | |||||||||||||
| Acidic | Glutamic Acid, Aspartic Acide | T1 |
median: 12.61 (7.47) in case, 12.81 (7.80) in control |
Ref | ||||||||||||
| T2 | 1.03 | 0.77 | 1.37 | |||||||||||||
| T3 | 0.94 | 0.63 | 1.42 | |||||||||||||
| Alcoholic | Serine, Threonine | T1 | median: 3.66 (2.25) in case, 3.77 (2.39) in control | Ref | ||||||||||||
| T2 | 0.98 | 0.74 | 1.30 | |||||||||||||
| T3 | 1.08 | 0.73 | 1.60 | |||||||||||||
| Small amino acids | Glycine, Alanine | T1 | median: 3.82 (2.59) in case, 3.95 (2.62) in control | Ref | ||||||||||||
| T2 | 1.06 | 0.80 | 1.41 | |||||||||||||
| T3 | 1.08 | 0.74 | 1.59 | |||||||||||||
| Essential | Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine | T1 | median: 16.46 (10.42) in case, 16.95 (11.01) in control | Ref | ||||||||||||
| T2 | 1.03 | 0.78 | 1.37 | |||||||||||||
| T3 | 1.10 | 0.75 | 1.60 | |||||||||||||
| Non-essential | Alanine, Arginine, Aspartic Acid, Cysteine, Glutamic Acid, Glycine, Proline, Serine, Tyrosine | T1 | median: 25.52 (15.32) in case, 25.83 (16.10) in control | Ref | ||||||||||||
| T2 | 1.01 | 0.76 | 1.35 | |||||||||||||
| T3 | 1.02 | 0.69 | 1.52 | |||||||||||||
| Total | - | T1 | median: 41.90 (26.27) in case, 42.80 (27.01) in control | Ref | ||||||||||||
| T2 | 1.02 | 0.77 | 1.36 | |||||||||||||
| T3 | 1.09 | 0.74 | 1.61 | |||||||||||||
| 8 | Rahemi. M-H., 2024 [29]/China/Population-based cross-sectional |
19–79 yr/ 11,192/ 45% |
Total | Glycine | T1 | - | - | gr/day | SBP equal to or exceeding 130 mmHg, or diastolic blood pressure equal to or exceeding 85 mmHg | - | - | 673/11192 | Age, gender, alcohol, consumption, smoking status, work intensity, educational status, monthly income, and BMI | Ref | ||
| T2 | 1.08 | 0.88 | 1.33 | |||||||||||||
| T3 | 0.70 | 0.56 | 0.88 | |||||||||||||
| Male | Glycine | T1 | Ref | |||||||||||||
| T2 | 1.39 | 1.03 | 1.87 | |||||||||||||
| T3 | 0.86 | 0.62 | 1.19 | |||||||||||||
| Female | Glycine | T1 | Ref | |||||||||||||
| T2 | 0.89 | 0.67 | 1.18 | |||||||||||||
| T3 | 0.62 | 0.46 | 0.84 | |||||||||||||
| Age < 60 yr | Glycine | T1 | Ref | |||||||||||||
| T2 | 1.35 | 1.02 | 1.78 | |||||||||||||
| T3 | 0.97 | 0.72 | 1.31 | |||||||||||||
| Age ≥ 60 yr | Glycine | T1 | Ref | |||||||||||||
| T2 | 0.85 | 0.65 | 1.11 | |||||||||||||
| T3 | 0.52 | 0.38 | 0.69 | |||||||||||||
| Total | Histidine | T1 | Ref | |||||||||||||
| T2 | 1.08 | 0.87 | 1.34 | |||||||||||||
| T3 | 0.80 | 0.64 | 0.99 | |||||||||||||
| Male | Histidine | T1 | Ref | |||||||||||||
| T2 | 1.15 | 0.85 | 1.56 | |||||||||||||
| T3 | 0.91 | 0.67 | 1.24 | |||||||||||||
| Female | Histidine | T1 | Ref | |||||||||||||
| T2 | 0.90 | 0.68 | 1.20 | |||||||||||||
| T3 | 0.68 | 0.51 | 0.92 | |||||||||||||
| Age < 60 yr | Histidine | T1 | Ref | |||||||||||||
| T2 | 1.13 | 0.85 | 1.51 | |||||||||||||
| T3 | 1.07 | 0.81 | 1.43 | |||||||||||||
| Age ≥ 60 yr | Histidine | T1 | Ref | |||||||||||||
| T2 | 0.90 | 0.69 | 1.18 | |||||||||||||
| T3 | 0.66 | 0.50 | 0.88 | |||||||||||||
| Total |
Glycine + Histidine |
T1 | Ref | |||||||||||||
| T2 | 1.07 | 0.87 | 1.32 | |||||||||||||
| T3 | 0.74 | 0.59 | 0.92 | |||||||||||||
| Male |
Glycine + Histidine |
T1 | Ref | |||||||||||||
| T2 | 1.28 | 0.95 | 1.73 | |||||||||||||
| T3 | 0.92 | 0.67 | 1.26 | |||||||||||||
| Female |
Glycine + Histidine |
T1 | Ref | |||||||||||||
| T2 | 0.78 | 0.59 | 1.04 | |||||||||||||
| T3 | 0.64 | 0.47 | 0.85 | |||||||||||||
| Age < 60 yr |
Glycine + Histidine |
T1 | Ref | |||||||||||||
| T2 | 1.26 | 0.94 | 1.67 | |||||||||||||
| T3 | 1.02 | 0.76 | 1.37 | |||||||||||||
| Age ≥ 60 yr |
Glycine + Histidine |
T1 | Ref | |||||||||||||
| T2 | 0.85 | 0.65 | 1.12 | |||||||||||||
| T3 | 0.57 | 0.42 | 0.76 | |||||||||||||
| Total |
Glycine + Histidine |
Low & Low | Ref | |||||||||||||
| Low & High | 1.08 | 0.70 | 1.66 | |||||||||||||
| High & Low | 0.99 | 0.60 | 1.63 | |||||||||||||
|
High & High |
0.73 | 0.61 | 0.87 | |||||||||||||
| 9 | Salimi, Z., 2024 [30]/Iran/Cross-sectional |
people with HTN: 53.45 ± 8.3 people with normal BP: 47.46 ± 8.35/ 4184 (2945 people with normal BP and 1239 with HTN)/ people with HTN: 700 (56.5%) people with normal BP: 1166 (39.59%) |
Branched chain amino acids | Branched chain amino acids | - | - | people with normal BP: 11.89, people with HTN:12.16 | gr/day | Systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg | - | - | - | Age and gender, education, marital status, job, physical activity, BMI, diabetes, intake of energy, and other amino acids | 1.01 | 0.96 | 1.04 |
| Leucine | Leucine | - | 5.28 ± 0.02, 5.26 ± 0.03 | 1.01 | 0.92 | 1.09 | ||||||||||
| Isoleucine | Isoleucine | - | 3.08 ± 0.01, 3.06 ± 0.02 | 1.01 | 0.87 | 1.16 | ||||||||||
| Valine | Valine | - | 3.63 ± 0.01, 3.61 ± 0.02 | 1.00 | 0.88 | 1.13 |
IQR Interquartile Range, SD Standard Deviation, Q Quartile, T Tertile, OR Odds Ratio, CI Confidence Interval, SBP Systolic Blood Pressure, SBP Systolic Blood Pressure, HTN Hypertension, BMI Body Mass Index
Table 3.
The description of eligible studies reporting the association between dietary amino acids and hypertension, including adjusted hazard ratio
| ID | Author, Year/Country/Study Type | Mean/Median of Age/ Sample Size (n)/ Male (n, %) |
Amino acid categories | Type of amino acid | Amino acid level | n amino acid group | Mean ± SD/median (IQR) amino acid group | Unit | Hypertension Criteria | Mean ± SD/Median (IQR) Systolic BP | Mean ± SD/Median (IQR) Diastolic BP | Incidence of hypertension | Adjustment for Confounder | Adjusted HR | Lower CI | Upper CI |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Altorf-van der Kuil, W., 2013 [24]/Netherlands/Cohort study/cress-sectional analysis |
66 ± 7/3086 = cross-sectional analysis/1080 = prospective analysis/40% (in people aged ≥ 55 yr) |
Glutamic acid | Glutamic acid | T1 | 603 | 19.7 | % of protein | - | - | - | 286.603 | Total energy, carbohydrates, SFAs, PUFAs, fiber, calcium, magnesium, sodium (only from food), and potassium (all continuous) | Ref | ||
| T2 | 604 | 20.7 | 312.604 | 1.18 | 0.99 | 1.41 | ||||||||||
| T3 | 603 | 21.8 | 275.603 | 1.02 | 0.83 | 1.26 | ||||||||||
| Arginine | Arginine | T1 | 603 | 5 | 289.603 | Ref | ||||||||||
| T2 | 604 | 5.3 | 289.604 | 1 | 0.83 | 1.19 | ||||||||||
| T3 | 603 | 5.6 | 295.603 | 1.06 | 0.85 | 1.31 | ||||||||||
| Lysine | Lysine | T1 | 603 | 6.4 | 277.603 | Ref | ||||||||||
| T2 | 604 | 6.8 | 286.604 | 1.01 | 0.84 | 1.21 | ||||||||||
| T3 | 603 | 7.2 | 310.603 | 1.15 | 0.93 | 1.43 | ||||||||||
| Arginine: lysine | Arginine: lysine | T1 | 603 | 0.72 | 314.603 | Ref | ||||||||||
| T2 | 604 | 0.77 | 276.604 | 0.81 | 0.67 | 0.97 | ||||||||||
| T3 | 603 | 0.84 | 283.603 | 0.86 | 0.69 | 1.07 | ||||||||||
| Cysteine | Cysteine | T1 | 603 | 1.4 | 291.603 | Ref | ||||||||||
| T2 | 604 | 1.4 | 291.604 | 0.95 | 0.79 | 1.14 | ||||||||||
| T3 | 603 | 1.5 | 291.603 | 0.98 | 0.77 | 1.24 | ||||||||||
| Tyrosine | Tyrosine | T1 | 603 | 3.5 | 310.603 | Ref | ||||||||||
| T2 | 604 | 3.7 | 275.604 | 0.85 | 0.71 | 1.02 | ||||||||||
| T3 | 603 | 3.8 | 288.603 | 0.92 | 0.73 | 1.15 | ||||||||||
| 2 |
Liu, Y., 2022 [26]/China/ Prospective cohort |
Men: 44.4 ± 14.2 Women: 44.8 ± 13.9/8491/ 3995 |
Branched-chain amino acids | Isoleucine | Q1 |
men:1001 women:1132 |
men: < 1.66 women: < 1.57 |
gr/day | SBP ≥ 140 mmHg, or DBP ≥ 90 mmHg, or use of antihypertensive medication |
Baseline men:117.3 ± 10.4 Baseline women:113.5 ± 11.9 At the end of follow up men:123.6 ± 15.4, At the end of follow up women:120.5 ± 17.0 |
Baseline men:76.3 ± 7.5 Baseline women:73.9 ± 8.1 At the end of follow up men:80.8 ± 10.5, At the end of follow up women:77.6 ± 10.5 |
men:272 (27.2%) women:257 (22.7%) |
Age, ethnicity, education, urban residents, diagnosed T2DM, physical activity, smoking, alcohol drinking, energy, carbohydrate, fat, protein, and salt intake | Ref | ||
| Q2 |
men:994 women:1119 |
men: 1.66–2.32 women:1.57–2.15 |
men:230 (23.1%) women:246 (22.0%) |
men:1.28 women:1.99 |
men:0.42 women:0.72 |
men:3.90 women:5.52 |
||||||||||
| Q3 |
men:997 women:1128 |
men: 2.32–3.06 women: 2.15–2.87 |
men:267 (26.8%) women:255 (22.6%) |
men:1.60 women:1.84 |
men:0.70 women:0.80 |
men:3.67 women:4.25 |
||||||||||
| Q4 |
men:1003 women:1117 |
men: ≥ 3.06 women: ≥ 2.87 |
men:386 (38.5%) women:346 (31.0%) |
men:1.14 women:1.36 |
men:1.01 women:1.20 |
men:1.29 women:1.54 |
||||||||||
| Leucine | Q1 |
men:998 women:1118 |
men: < 2.94 women: < 2.76 |
men:272 (27.3%) women:259 (23.2%) |
Ref | |||||||||||
| Q2 |
men:1004 women:1127 |
men: 2.94–4.12 women: 2.76–3.82 |
men:238 (23.7%) women:241 (21.4%) |
men:0.84 women:2.06 |
men:0.48 women:1.10 |
men:1.47 women:3.85 |
||||||||||
| Q3 |
men:997 women:1133 |
men: 4.12–5.54 women: 3.82–5.15 |
men:264 (26.5%) women:255 (22.5%) |
men:1.16 women:1.05 |
men:0.74 women:0.67 |
men:1.81 women:1.64 |
||||||||||
| Q4 |
men:996 women:1118 |
men: ≥ 5.54 women: ≥ 5.15 |
men:381 (38.3%) women:349 (31.2%) |
men:1.09 women:1.15 |
men:1.03 women:1.08 |
men:1.15 women:1.23 |
||||||||||
| Valine | Q1 |
men:999 women:1122 |
men: < 1.96 women: < 1.85 |
men:263 (26.3%) women:250 (22.3%) |
Ref | |||||||||||
| Q2 |
men:1000 women:1123 |
men: 1.96–2.71 women: 1.85–2.52 |
men:237 (23.7%) women:236 (21.0%) |
men:0.63 women:1.86 |
men:0.26 women:0.72 |
men:1.53 women:4.85 |
||||||||||
| Q3 |
men:991 women:1126 |
men: 2.71–3.61 women: 2.52–3.37 |
men:282 (28.5%) women:267 (23.7%) |
men:2.94 women:0.86 |
men:1.30 women:0.42 |
men:4.76 women:1.76 |
||||||||||
| Q4 |
men:1005 women:1125 |
men: ≥ 3.61 women: ≥ 3.37 |
men:373 (37.1%) women:351 (31.2%) |
men:1.15 women:1.25 |
men:1.03 women:1.13 |
men:1.27 women:1.39 |
||||||||||
| Isoleucine | - |
men:3995 women:4496 |
- |
men:1155 (28.9%) women:1104 (24.5%) |
men:1.24 women:1.29 |
men:1.14 women:1.19 |
men:1.35 women:1.40 |
|||||||||
| Leucine | - |
men:3995 women:4496 |
- |
men:1155 (28.9%) women:1104 (24.5%) |
men:1.23 women:1.27 |
men:1.13 women:1.18 |
men:1.33 women:1.38 |
|||||||||
| Valine | - |
men:3995 women:4496 |
- |
men:1155 (28.9%) women:1104 (24.5%) |
men:1.23 women:1.28 |
men:1.13 women:1.18 |
men:1.33 women:1.38 |
|||||||||
| 3 |
Yu, L., 2024 [31]/ China/Open cohort |
43.0 ± 14.6/ 14,883/7020 (47%) |
Branched-chain amino acids | BCAAs | 1st–5th | 744 | < 6.48 | gr/day | Patient-reported physician diagnosis and/or use of antihypertensive medication. Previous studies have shown that self-reported hypertension was an effective tool | 138 (36.1/1000 person years) | Age, gender, smoking status, alcohol consumption, BMI, energy intake, salt intake, and physical activity at baseline | 0.98 | 0.79 | 1.22 | ||
| 6th–20th | 2220 | 6.48–8.85 | 435 (25.5) | 0.98 | 0.85 | 1.14 | ||||||||||
| 21st–40th | 2969 | 8.85–10.69 | 525 (19.1) | 1.04 | 0.91 | 1.19 | ||||||||||
| 41st–60th | 2964 | 10.69–12.41 | 489 (16.4) | Ref | ||||||||||||
| 61st–80th | 2969 | 12.41–14.62 | 540 (18.3) | 1.16 | 1.01 | 1.32 | ||||||||||
| 81st–95th | 2227 | 14.62–18.73 | 410 (21.0) | 1.30 | 1.13 | 1.50 | ||||||||||
| 96th–100th | 740 | > 18.73 | 155 (33.4) | 1.60 | 1.32 | 1.95 | ||||||||||
| Isoleucine | Isoleucine | 1st–5th | 742 | < 1.65 | 140 (37.5/1000 person years) | 1.04 | 0.84 | 1.29 | ||||||||
| 6th–20th | 2223 | 1.65–2.28 | 440 (26.3) | 0.99 | 0.85 | 1.14 | ||||||||||
| 21st–40th | 2941 | 2.28–2.76 | 529 (19.4) | 1.04 | 0.91 | 1.18 | ||||||||||
| 41st–60th | 2989 | 2.76–3.21 | 506 (16.9) | Ref | ||||||||||||
| 61st–80th | 2986 | 3.21–3.79 | 514 (17.3) | 1.09 | 0.95 | 1.24 | ||||||||||
| 81st–95th | 2209 | 3.79–4.82 | 406 (20.5) | 1.26 | 1.09 | 1.45 | ||||||||||
| 96th–100th | 743 | > 4.82 | 157 (32.8) | 1.58 | 1.30 | 1.92 | ||||||||||
| Leucine | Leucine | 1st–5th | 742 | < 2.84 | 132 (34.2/1000 person years) | 0.90 | 0.73 | 1.12 | ||||||||
| 6th–20th | 2224 | 2.84–3.90 | 448 (25.7) | 0.96 | 0.84 | 1.11 | ||||||||||
| 21st–40th | 2960 | 3.90–4.73 | 501 (18.0) | 0.95 | 0.83 | 1.09 | ||||||||||
| 41st–60th | 2974 | 4.73–5.52 | 514 (17.3) | Ref | ||||||||||||
| 61st–80th | 2966 | 5.52–6.53 | 535 (18.5) | 1.11 | 0.97 | 1.26 | ||||||||||
| 81st–95th | 2227 | 6.53–8.41 | 411 (21.3) | 1.24 | 1.08 | 1.43 | ||||||||||
| 96th–100th | 740 | > 8.41 | 151 (31.9) | 1.48 | 1.21 | 1.80 | ||||||||||
| Valine | Valine | 1st–5th | 733 | < 1.93 | 134 (35.9/1000 person years) | 0.92 | 0.74 | 1.15 | ||||||||
| 6th–20th | 2248 | 1.93–2.63 | 444 (26.2) | 0.95 | 0.82 | 1.10 | ||||||||||
| 21st–40th | 2964 | 2.63–3.17 | 513 (18.6) | 0.96 | 0.84 | 1.10 | ||||||||||
| 41st–60th | 2972 | 3.17–3.68 | 509 (17.1) | Ref | ||||||||||||
| 61st–80th | 2968 | 3.68–4.32 | 539 (18.3) | 1.10 | 0.96 | 1.25 | ||||||||||
| 81st–95th | 2202 | 4.32–5.49 | 401 (20.5) | 1.26 | 1.09 | 1.45 | ||||||||||
| 96th–100th | 746 | > 5.49 | 152 (31.6) | 1.53 | 1.25 | 1.86 |
IQR Interquartile Range, SD Standard Deviation, Q Quartile, T Tertile, HR Hazard Ratio, CI Confidence Interval, SBP Systolic Blood Pressure, SBP Systolic Blood Pressure, HTN Hypertension, T2DM Type 2 Diabetes Mellitus
Table 4.
The description of eligible studies reporting the association between dietary amino acids and hypertension, including mean difference
| ID | Author, Year/Country/Study Type | Mean/Median of Age/Sample Size (n)/Male (n, %) | Type of amino acid | n amino acid group | Mean ± SD/median (IQR) amino acid group | Unit | Hypertension Criteria | Adjustment for Confounder | Mean Difference |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Stamler, J., 2009 [14]/17 random population samples in China, Japan, U.K., U.S.A/Cross-sectional (persons 40–59 yr) |
40–49 y (n = 2365) 50–59 y (n = 2315)/ 4680/ 2359 |
Glutamic Acid | 4680 | Two-SD higher glutamic acid intake = 9.60 g/day | % of protein | Non-hypertensive persons had SBP, 140 mm Hg and DBP, 90 mm Hg and were not taking an antihypertensive medication | Sample, age, sex, special diet (yes or no), supplement intake (yes or no), cardiovascular disease or diabetes diagnosis (yes or no), physical activity (medium plus heavy; h/d), family history of high blood pressure (yes, no, or unknown), urinary sodium and urinary potassium (mmol/24 h), 14-d alcohol (g/d), cholesterol (mg/1000 kJ), and total SFA and total PUFA (percentage of kJ) |
SBP: −1.94 DBP: −1.19 |
| 2 |
Stamler, J., 2013 [25]/ 17 random population samples in China, Japan, U.K., U.S.A/ Cross-sectional (persons 40–59 yr) |
40–49 y old (n = 2365) 50–59 y old (n = 2315)/ 4680/ Men (n = 2359) |
Glycine | 4680 | Two-SD higher glycine intake = 2.39 | % of protein | Non-hypertensive persons had SBP, 140 mm Hg and DBP, 90 mm Hg and were not taking an antihypertensive medication | Sample, age, sex, special diet (yes or no), supplement intake (yes or no), cardiovascular disease or diabetes diagnosis (yes or no), physical activity (medium plus heavy; h/d), family history of high blood pressure (yes, no, or unknown) Adjusted for height and weight |
SBP: 2.20 DBP: 1.05 |
| Alanine | Two-SD higher glycine intake = 2.62 |
SBP: 1.32 DBP: 0.53 |
IQR Interquartile Range, SD Standard Deviation, SBP Systolic Blood Pressure, SBP Systolic Blood Pressure
Results
A total of 86 records were identified through database searching. After the removal of duplicates, 53 records were screened based on their title and abstract. Of these, 23 full-text articles were assessed for eligibility, and 16 studies were ultimately included. The primary reasons for excluding full-text articles were wrong outcome or wrong exposure. This selection process is detailed in the PRISMA flow diagram (Fig. 1). The final 16 observational studies, encompassing 57,913 participants and published up to September 30, 2025, were included in the present study. All included studies (n = 16) were assessed as high quality using the NOS, with scores of ≥ 7. Most studies included participants with a wide range of mean ages, from adolescents aged 14.7 years to adults aged 66 years. The studies were published between 2009 and 2024. One study was conducted in adolescents [21]. The most frequently assessed amino acids were the branched-chain amino acids (isoleucine, leucine, valine; n = 9 studies), followed by aromatic amino acids (n = 7 studies) and glycine (n = 4 studies). In most studies, amino acid intake was measured in grams per day. Two studies reported intake in mg/day [22, 23], and three studies reported intake as a percentage of total protein [14, 24, 25]. Three studies reported the association between dietary amino acids and hypertension or blood pressure using beta coefficients (crude and/or adjusted) [21, 22, 26], eight studies reported adjusted odds ratios [7, 18, 23, 27–30], three studies reported adjusted hazard ratios [24, 26, 31], and two studies reported mean differences [14, 25].
Fig. 1.
Flow diagram of the study selection process and including publications
The majority were prospective cohort studies (n = 8), which followed participants over time to ascertain the incidence of hypertension. There were also five cross-sectional studies, which assessed exposure and outcome at a single time point. The remaining studies used other designs, including a nested case–control study [28] and an observational cohort based on a secondary analysis of a clinical trial [23]. A significant proportion of the studies (n = 7) were conducted in Iran. Three studies were conducted in China, and one was from the Netherlands. Two studies were multinational: one enrolled participants from eight European countries [21, 29], and another included samples from China, Japan, the UK, and the USA [14, 25]. A key focus was on sex-specific associations, with three studies [21, 26, 29] reporting results stratified by sex. Age was another important stratifier, with one study focusing on adolescents and another [29] analyzing results for participants above and below 60 years of age. Furthermore, two studies investigated unique clinical subpopulations: one enrolled individuals with spinal cord injury [22], and another focused on patients with established cardiovascular disease [23]. Further details of the studies are shown in Tables 1–4.
Association between dietary amino acid and hypertension
Adjusted beta coefficient
Based on findings from three studies, the association between dietary intake of isoleucine, leucine, and valine and SBP was positive in both men and women, indicating that SBP increased with higher consumption of these amino acids. However, this association was statistically significant only in men. In contrast, the association between these BCAAs and DBP in women was negative, suggesting that DBP decreased with higher intake, though this result was not statistically significant. Overall, the beta coefficients revealed generally weak and inconsistent linear relationships between individual amino acids and blood pressure levels in cross-sectional analyses, with only a few isolated significant findings (Table 1).
Adjusted odds ratio
Findings from multiple studies showed clearer patterns when evaluating the binary outcome of hypertension diagnosis. Higher intake of BCAAs, valine, and aromatic amino acids such as phenylalanine was consistently associated with a statistically significant increase in the odds of hypertension. For example, in one study, the highest quartile of valine intake was associated with an OR of 1.61 (95% CI: 1.10–2.36) for hypertension. Conversely, higher dietary intake of glycine, both alone and in combination with histidine, was identified as a protective factor. For instance, the highest tertile of glycine intake was associated with a significant reduction in the odds of hypertension (OR = 0.69; 95% CI: 0.49–0.96). Similarly, the combination of high glycine and high histidine intake was linked to lower odds of hypertension (OR = 0.73; 95% CI: 0.61–0.87). These results suggest that specific amino acids may differentially influence hypertension risk (Table 2). As shown in Fig. 2, the risk of hypertension increased with higher dietary intake of branched-chain, aromatic, and alcoholic amino acids (AAAs), as well as proline and other small amino acids. The pooled adjusted OR for the second, third, and fourth quartiles were 1.37 (95% CI: 1.14–1.66), 1.50 (95% CI: 1.22–1.85), and 1.66 (95% CI: 1.31–2.11), respectively. In contrast, glycine intake was associated with a protective effect, with a pooled OR of 0.75 (95% CI: 0.64–0.89) in the third tertile (Fig. 3). A similar, though non-significant, protective trend was observed for histidine (pooled OR: 0.85; 95% CI: 0.70–1.03) (Fig. 4).
Fig. 2.
Forest plot of the effect of dietary branched chain, alcoholic, aromatic amino acids, proline, and small amino acids on the risk of hypertension based on adjusted odds ratio
Fig. 3.
Forest plot of the effect of dietary glycine on the risk of hypertension based on adjusted odds ratio
Fig. 4.
Forest plot of the effect of dietary histidine on the risk of hypertension based on adjusted odds ratio
Adjusted hazard ratio
Prospective data from three cohort studies show a significant positive association between high intake of BCAAs and an increased risk of hypertension, with a clear dose–response relationship. The most robust evidence comes from Yu et al. (2024), which showed that participants in the highest percentile (96th-100th) of BCAA intake had a substantially higher risk of hypertension compared to the reference group (41st-60th percentile). The hazard ratios were 1.60 (95% CI: 1.32–1.95) for total BCAAs, 1.58 (95% CI: 1.30–1.92) for isoleucine, 1.48 (95% CI: 1.21–1.80) for leucine, and 1.53 (95% CI: 1.25–1.86) for valine. This aligns with findings from Liu et al. (2022), where the highest quartile (Q4) of BCAA intake was also positively associated with hypertension risk (e.g., isoleucine: Men HR 1.14, 95% CI 1.01–1.29; Women HR 1.36, 95% CI 1.20–1.54). In contrast, the earlier study by Altorf-van der Kuil et al. [24] found no significant positive associations for most amino acids, including BCAAs, but reported a significant inverse association for the second tertile of the arginine-to-lysine ratio (HR: 0.81, 95% CI: 0.67–0.97) (Table 3).
Mean difference
Population-level analyses further supported the protective role of certain amino acids. Significantly higher intake of both glutamic acid and glycine was associated with clinically meaningful reductions in systolic and diastolic blood pressure. For instance, a two-standard deviation increase in glutamic acid intake was associated with a mean difference of –1.94 mmHg in SBP and –1.19 mmHg in DBP. Similarly, a comparable increase in glycine intake was linked to a mean difference of –2.20 mmHg in SBP and –1.00 mmHg in DBP. These findings highlight the potential beneficial effects of specific amino acids on blood pressure regulation at the population level (Table 4).
Discussion
This systematic review and meta-analysis of 16 observational studies provides a comprehensive synthesis of the evidence linking dietary amino acids to hypertension. The principal finding is that specific amino acids have distinct and significant associations with HTN risk. Higher intake of branched-chain amino acids (isoleucine, leucine, valine) and aromatic amino acids (e.g., phenylalanine) was consistently associated with an increased risk of hypertension. This was evidenced by a clear dose–response relationship in our meta-analysis of odds ratios, where the highest quartile of intake conferred a 66% greater odds of HTN, and by significant hazard ratios in prospective studies, indicating a direct long-term risk. Conversely, glycine intake showed a consistent protective effect, associated with a 25% reduction in the odds of hypertension and clinically meaningful reductions in systolic and diastolic blood pressure.
The distinct associations observed for different amino acids may reflect broader dietary patterns [32]. Branched-chain amino acids are particularly abundant in animal-based proteins such as red meat, eggs, and dairy products [33]. Similarly, aromatic amino acids like phenylalanine are found in high concentrations in meat, soy, and dairy. Therefore, high intake of these amino acids could serve as a biomarker for a diet rich in specific animal protein sources, which have been independently associated with hypertension risk [34]. Conversely, the protective association of glycine, which is high in collagen, gelatin, and the skin of poultry and pork [35], suggests that the specific composition of protein sources, rather than total protein intake alone, is a critical factor [32, 36].
In addition, the association between BCAAs and elevated HTN risk aligns with existing pathophysiological hypotheses. High plasma BCAA levels are known to promote insulin resistance through mechanisms such as mTOR activation and impairment of mitochondrial function [7, 12]. Subsequent hyperinsulinemia can elevate blood pressure via increased renal sodium reabsorption and activation of the sympathetic nervous system [37]. Furthermore, BCAAs may influence central nervous system regulation of blood pressure by competing with tryptophan for transport across the blood–brain barrier, potentially reducing the synthesis of serotonin, a neurotransmitter involved in vasodilation and blood pressure regulation [7, 13, 38].
The detrimental association observed with aromatic amino acids (AAAs) may be linked to their role as precursors for vasoactive catecholamines (dopamine, norepinephrine) [39–41]. Increased AAA availability could elevate the production of these sympathetic neurotransmitters, leading to vasoconstriction and increased cardiac output. An alternative mechanism involves the cofactor tetrahydrobiopterin (BH4), which is essential for both nitric oxide (NO) synthase and AAA metabolism. Excessive AAA intake may divert BH4 away from NO production, leading to endothelial dysfunction, increased vascular resistance, and hypertension [42, 43].
The consistent protective effect of glycine is a notable finding. Glycine has demonstrated anti-inflammatory, antioxidant, and endothelium-protective properties in experimental studies. It may improve endothelial function by enhancing the availability of nitric oxide, thereby promoting vasodilation [43, 44]. Our results, which show that higher glycine intake is associated with significant reductions in both SBP and DBP at the population level, strongly support its potential beneficial role in blood pressure regulation.
Our findings also provide a potential explanatory association between broader dietary patterns and HTN. The adverse associations of BCAAs and AAAs, which are abundant in animal proteins such as red meat, and the beneficial association of glycine, more prevalent in collagen and gelatin (often found in diets with varied protein sources), offer mechanistic insight into why some protein sources may be detrimental while others are protective for cardiovascular health [25, 45, 46].
This study has several limitations. The number of studies available for each specific amino acid and analysis was limited, restricting the power of some subgroup analyses. A significant constraint was the methodological heterogeneity across the included studies, including variations in how amino acid intake was measured (e.g., grams per day vs. percentage of protein) and the different effect measures reported (beta coefficients, ORs, HRs), which complicated direct comparison and pooling of data. Third, while the quality assessment indicated that most included studies were of high quality, the observational nature of all evidence means that residual confounding cannot be ruled out. Furthermore, the observed associations for some amino acids, such as the sex-specific findings for BCAAs, warrant further investigation to understand the underlying reasons for these differences.
Conclusion
This analysis shows that specific dietary amino acids have distinct and significant associations with HTN risk. Higher intake of branched-chain amino acids (isoleucine, leucine, valine) and aromatic amino acids (phenylalanine) is consistently associated with increased HTN risk, as shown by pooled odds ratios and prospective hazard ratios. Conversely, glycine intake consistently shows a protective effect, being associated with significantly lower odds of HTN and clinically relevant reductions in blood pressure. However, the evidence is complicated by methodological limitations. Therefore, dietary recommendations concerning amino acid intake for HTN prevention should be approached with caution. Future research using standardized methodologies is essential to confirm these associations and clarify the underlying mechanisms. This will provide a clearer evidence base for translating these findings into public health and clinical practice.
Supplementary Information
Acknowledgements
Not applicable.
Abbreviations
- AAAs
Aromatic Amino Acids
- BCAA
Branched-Chain Amino Acids
- BH4
Tetrahydrobiopterin
- CKD
Chronic Kidney Disease
- CI
Confidence Interval
- HR
Hazard Ratio
- HTN
Hypertension
- MeSH
Medical Subject Headings
- NO
Nitric Oxide
- NOS
Newcastle–Ottawa Scale
- OR
Odds Ratio
Authors’ contributions
N. I, P. A: Contribution to study concept and design, acquisition, analysis, and interpretation of data, drafting of the manuscript R.H, A. SH, H.F, M.N: Contribution to analysis and interpretation of data, analysis and interpretation of data, drafting of the manuscript All authors have read and approved the manuscript.
Funding
No funding.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Declarations
Ethics approval and consent to participate
All procedures performed in the study were approved by the Research Ethics Committee of Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences (IR.SBMU.ENDOCRINE.REC.1402.089). Also informed consent was obtained from all participants. All methods were carried out in accordance with relevant guidelines and regulations.
Consent to publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Contributor Information
Neda Izadi, Email: neda.izady@yahoo.com.
Parisa Amiri, Email: amiri@endocrine.ac.ir.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.