Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Fast track – ISH2022 KYOTO
  • Published:

Urinary metabolomics, dietary salt intake and blood pressure: the African-PREDICT study

Hypertension Research volume 46, pages 175–186 (2023)Cite this article

Abstract

In Black populations excessive salt intake may exacerbate the genetic predisposition to hypertension and promote the early onset of cardiovascular disease. Ethnic differences in the interaction between sodium intake and the metabolome may play a part in hypertension and cardiovascular disease development. We determined (1) urinary amino acid and acylcarnitine profiles of young Black and White adults according to low, moderate, and high dietary salt intake, and (2) investigated the triad of salt intake, systolic blood pressure (SBP), and the associated metabolomics profile. This study included 447 White and 380 Black adults aged 20–30 years from the African-PREDICT study. Estimated salt intake was determined from 24-hour urinary sodium levels. Urinary amino acids and acylcarnitines were measured using liquid chromatography-tandem mass spectrometry. Black adults exhibited no significant differences in SBP, amino acids, or acylcarnitines across low (<5g/day), moderate (5–10g/day), and high (>10g/day) salt intake. White adults with a high salt intake had elevated SBP compared to those with low or moderate intakes (p < 0.001). Furthermore, gamma-aminobutyric acid (GABA) (q = 0.020), citrulline (q = 0.020), glutamic acid (q = 0.046), serine (q = 0.054) and proline (q = 0.054) were lowest in those with higher salt intake. Only in White and not Black adults did we observe inverse associations of clinic SBP with GABA (Adj. R2 = 0.34; Std. β = −0.133; p = 0.003), serine (Adj. R2 = 0.33; Std. β = −0.109; p = 0.014) and proline (Adj. R2 = 0.33; Std. β = −0.109; p = 0.014). High salt intake in White, but not in black adults, were related to metabolomic changes and may contribute to pathophysiological mechanisms associated with increased BP.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global burden of cardiovascular diseases and risk factors, 1990-2019: Update From the GBD 2019 Study. J Am Coll Cardiol. 2020;76:2982–3021.

    Article  Google Scholar 

  2. Said MA, Verweij N, van der Harst P. Associations of combined genetic and lifestyle risks with incident cardiovascular disease and diabetes in the UK Biobank Study. JAMA Cardiol. 2018;3:693–702.

    Article  Google Scholar 

  3. Qiao J, Lin X, Wu Y, Huang X, Pan X, Xu J, et al. Global burden of non-communicable diseases attributable to dietary risks in 1990-2019. J Hum Nutr Dietetics. 2022;35:202–13.

    Article  Google Scholar 

  4. Schutte AE Ethnicity and cardiovascular disease. Textbook of Vascular Medicine: Springer; 2019. pp. 287-959

  5. Elijovich F, Weinberger MH, Anderson CA, Appel LJ, Bursztyn M, Cook NR, et al. Salt sensitivity of blood pressure: a scientific statement from the American Heart Association. Hypertension. 2016;68:e7–e46.

    Article  CAS  Google Scholar 

  6. Schutte AE, Botha S, Fourie CMT, Gafane-Matemane LF, Kruger R, Lammertyn L, et al. Recent advances in understanding hypertension development in sub-Saharan Africa. J Hum Hypertens. 2017;31:491–500.

    Article  CAS  Google Scholar 

  7. He FJ, Tan M, Ma Y, MacGregor GA. Salt reduction to prevent hypertension and cardiovascular disease: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020;75:632–47.

    Article  CAS  Google Scholar 

  8. Chen L, He FJ, Dong Y, Huang Y, Wang C, Harshfield GA, et al. Modest sodium reduction increases circulating short-chain fatty acids in untreated hypertensives. Hypertension. 2020;76:73–9.

    Article  CAS  Google Scholar 

  9. Derkach A, Sampson J, Joseph J, Playdon MC, Stolzenberg-Solomon RZ. Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)-Sodium Feeding Study. Am. Clin Nutr. 2017;106:1131–41.

    CAS  Google Scholar 

  10. Jablonski KL, Klawitter J, Chonchol M, Bassett CJ, Racine ML, Seals DR. Effect of dietary sodium restriction on human urinary metabolomic profiles. Clin J Am Soc Nephrol. 2015;10:1227–34.

    Article  CAS  Google Scholar 

  11. Chen L, He FJ, Dong Y, Huang Y, Harshfield GA, Zhu H. Sodium reduction, metabolomic profiling, and cardiovascular disease risk in untreated black hypertensives. Hypertension. 2019;74:194–200.

    Article  CAS  Google Scholar 

  12. Schutte AE, Gona PN, Delles C, Uys AS, Burger A, Mels CM, et al. The African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT): Design, recruitment and initial examination. Eur. J Prev Cardiol. 2019;26:458–70.

    Article  Google Scholar 

  13. WHO/PAHO Regional Expert Group for Cardiovascular Disease Prevention through Population‐wide Dietary Salt Reduction. Protocol for population level sodium determination in 24‐hour urine samples. World Health Organization Geneva, Switzerland; 2010.

  14. Stevens LA, Claybon MA, Schmid CH, Chen J, Horio M, Imai E, et al. Evaluation of the Chronic Kidney Disease Epidemiology Collaboration equation for estimating the glomerular filtration rate in multiple ethnicities. Kidney Int. 2011;79:555–62.

    Article  Google Scholar 

  15. Stolarz-Skrzypek K, Kuznetsova T, Thijs L, Tikhonoff V, Seidlerová J, Richart T, et al. Fatal and nonfatal outcomes, incidence of hypertension, and blood pressure changes in relation to urinary sodium excretion. JAMA. 2011;305:1777–85.

    Article  CAS  Google Scholar 

  16. Strauss-Kruger M, Kruger R, Jansen Van Vuren E, Jacobs A, Louw R, Mels C Identifying a metabolomics profile associated with masked hypertension in two independent cohorts: Data from the African-PREDICT and SABPA studies. Hypertension Research 2022; https://doi.org/10.1038/s41440-022-01010-2.

  17. World Health Organization. Guideline: Sodium intake for adults and children. World Health Organization; 2012.

  18. Paapstel K, Kals J. Metabolomics of arterial stiffness. Metabolites. 2022;1212:370 https://doi.org/10.3390/metabo12050370.

    Article  CAS  Google Scholar 

  19. Breet Y, Huisman HW, Kruger R, Van Rooyen JM, Gafane-Matemane LF, Ware LJ, et al. Pulse pressure amplification and its relationship with age in young, apparently healthy black and white adults: the African-PREDICT study. 2017; 249:387-91.

  20. Mokwatsi GG, Schutte AE, Kruger R. Ethnic differences regarding arterial stiffness of 6‐8‐year-old black and white boys. J Hypertens. 2017;35:960–67.

    Article  CAS  Google Scholar 

  21. Erasmus D, Mels CM, Louw R, Lindeque JZ, Kruger RJP. Urinary metabolites and their link with premature arterial stiffness in black boys: the ASOS study. Pulse. 2018;6:144–53.

    Article  Google Scholar 

  22. Rédei GP Glucogenic Amino Acids. In: Rédei GP, editor. Encyclopedia of genetics, genomics, proteomics and informatics. Dordrecht: Springer; 2008. p. 803.

  23. Chung ST, Hsia DS, Chacko SK, Rodriguez LM, Haymond MW. Increased gluconeogenesis in youth with newly diagnosed type 2 diabetes. Diabetologia. 2015;58:596–603.

    Article  CAS  Google Scholar 

  24. Chung ST, Courville AB, Onuzuruike AU, Galvan-De La Cruz M, Mabundo LS, DuBose CW, et al. Gluconeogenesis and risk for fasting hyperglycemia in Black and White women. JCI insight. 2018;3:e121495.

    Article  Google Scholar 

  25. Balakrishna Y, Manda S, Mwambi H, van Graan A. Identifying nutrient patterns in south african foods to support national nutrition guidelines and policies. Nutrients. 2021;13:3194.

    Article  CAS  Google Scholar 

  26. Carmichael CY, Wainford RD. Hypothalamic signaling mechanisms in hypertension. Curr Hypertens Rep. 2015;17:39.

    Article  Google Scholar 

  27. Ngo D-H, Vo TS. An updated review on pharmaceutical properties of gamma-aminobutyric acid. Molecules. 2019;24:2678.

    Article  CAS  Google Scholar 

  28. Stamler J, Brown IJ, Daviglus ML, Chan Q, Kesteloot H, Ueshima H, et al. Glutamic acid, the main dietary amino acid, and blood pressure: the INTERMAP Study (International Collaborative Study of Macronutrients, Micronutrients and Blood Pressure). Circulation. 2009;120:221–8.

    Article  CAS  Google Scholar 

  29. Jennings A, MacGregor A, Welch A, Chowienczyk P, Spector T, Cassidy A. Amino acid intakes are inversely associated with arterial stiffness and central blood pressure in women. J Nutr. 2015;145:2130–8.

    Article  CAS  Google Scholar 

  30. McGee MA, Abdel-Rahman AA. N-Methyl-D-Aspartate receptor signaling and function in cardiovascular tissues. J Cardiovasc Pharm. 2016;68:97–105.

    Article  CAS  Google Scholar 

  31. Shabeeh H, Khan S, Jiang B, Brett S, Melikian N, Casadei B, et al. Blood pressure in healthy humans is regulated by neuronal NO synthase. Hypertension. 2017;69:970–6.

    Article  CAS  Google Scholar 

  32. Dietrich S, Floegel A, Weikert C, Prehn C, Adamski J, Pischon T, et al. Identification of serum metabolites associated with incident hypertension in the European Prospective Investigation Into Cancer and Nutrition-Potsdam Study. Hypertension. 2016;68:471–7.

    Article  CAS  Google Scholar 

  33. Louca P, Nogal A, Moskal A, Goulding NJ, Shipley MJ, Alkis T, et al. Cross-sectional blood metabolite markers of hypertension: a multicohort analysis of 44,306 individuals from the COnsortium of METabolomics Studies. Metabolites. 2022;12:601.

    Article  CAS  Google Scholar 

  34. Maralani MN, Movahedian A, Javanmard Sh H. Antioxidant and cytoprotective effects of L-Serine on human endothelial cells. Res Pharm Sci. 2012;7:209–15.

    Google Scholar 

  35. Teymoori F, Asghari G, Farhadnejad H, Nazarzadeh M, Atifeh M, Mirmiran P, et al. Various proline food sources and blood pressure: substitution analysis. Int J Food Sci Nutr. 2019;71:1–9.

    Google Scholar 

  36. Karna E, Szoka L, Huynh TYL, Palka JA. Proline-dependent regulation of collagen metabolism. Cell Mol Life Sci. 2020;77:1911–8.

    Article  CAS  Google Scholar 

  37. Charlton KE, Schutte AE, Wepener L, Corso B, Kowal P, Ware LJ. Correcting for intra-individual variability in sodium excretion in spot urine samples does not improve the ability to predict 24 h urinary sodium excretion. Nutrients. 2020;12:2026.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to all individuals who voluntarily participated in the African-PREDICT study. The dedication of the support and research staff as well as students at the Hypertension Research and Training Clinic at the North-West University are also duly acknowledged.

Funding

The research funded in this manuscript is part of an ongoing larger research project financially supported by the South African Medical Research Council (SAMRC) with funds from National Treasury under its Economic Competitiveness and Support Package; the South African Research Chairs Initiative (SARChI) of the Department of Science and Technology and National Research Foundation (NRF) of South Africa (GUN 86895); SAMRC with funds received from the South African National Department of Health, GlaxoSmithKline R&D (Africa Non-Communicable Disease Open Lab grant), the UK Medical Research Council and with funds from the UK Government’s Newton Fund; and corporate social investment grants from Pfizer (South Africa), Boehringer-Ingelheim (South Africa), Novartis (South Africa), the Medi Clinic Hospital Group (South Africa) and in-kind contributions of Roche Diagnostics (South Africa). This work is based on the research supported in part by the NRF of South Africa (Grant Number: UID: 138499). Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors, and therefore, the NRF does not accept any liability in this regard.

Author information

Authors and Affiliations

  1. Hypertension in Africa Research Team (HART), North-West University, Potchefstroom, 2520, North-West Province, South Africa

    Michél Strauss-Kruger, Ruan Kruger, Gontse Mokwatsi, Lebo Gafane-Matemane, Adriaan Jacobs, Aletta E. Schutte & Carina Mels

  2. MRC Research Unit for Hypertension and Cardiovascular Disease, North-West University, Potchefstroom, 2520, North-West Province, South Africa

    Michél Strauss-Kruger, Tertia van Zyl, Marlien Pieters, Ruan Kruger, Gontse Mokwatsi, Lebo Gafane-Matemane, Adriaan Jacobs, Aletta E. Schutte & Carina Mels

  3. Centre of Excellence for Nutrition, North-West University, Potchefstroom, 2520, South Africa

    Tertia van Zyl & Marlien Pieters

  4. Hypertension in Africa Research Team (HART), North-West University, Mahikeng, 2745, North-West Province, South Africa

    Hlengiwe Mbongwa

  5. School of Population Health, University of New South Wales, Sydney, NSW, 2052, Australia

    Aletta E. Schutte

  6. The George Institute for Global Health, Sydney, NSW, 2042, Australia

    Aletta E. Schutte

  7. Human Metabolomics, North-West University, Potchefstroom, 2520, North-West Province, South Africa

    Roan Louw

Authors
  1. Michél Strauss-Kruger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tertia van Zyl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marlien Pieters
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ruan Kruger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gontse Mokwatsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lebo Gafane-Matemane
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hlengiwe Mbongwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Adriaan Jacobs
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Aletta E. Schutte
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Roan Louw
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Carina Mels
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carina Mels.

Ethics declarations

Conflict of interest

TvZ, MP, RK, LGM, GM, HM, AJ, RL and CM reported no COI. Honoraria (lecture fees): AES (Abbott, Servier); Research Funding: AES (Medical Research Future Fund, Australia). Scholarship or donation: MSK (Postdoctoral grant from the National Research Foundation, South Africa).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Strauss-Kruger, M., van Zyl, T., Pieters, M. et al. Urinary metabolomics, dietary salt intake and blood pressure: the African-PREDICT study. Hypertens Res 46, 175–186 (2023). https://doi.org/10.1038/s41440-022-01071-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-022-01071-3

Keywords

Search

Advanced search

Quick links