Systematic review/meta-analysis and a cross-sectional study to assess effects of potassium supplementation on the renin-angiotensin-aldosterone system (RAAS) and blood pressure
Authors: McNally R J , Farukh B , Faconti L , Chowienczyk P 
Published: November 2023

Abstract

Introduction
Nutritional medicine plays a key role in disease prevention and treatment, and we pharmacists must consider our contribution beyond our role in dispensing. Apart from the Dietary Approaches to Stop Hypertension (DASH) diet1, there is a paucity of data on the benefits of nutritional interventions in hypertension with no clear recommendation on potassium in the NICE guidelines. Potassium has been an area of interest in clinical medicine over the decades because of its effect on cardiovascular disease. However, its mechanism of action is poorly understood, and it is unclear it differs between different ethnic groups. Dietary potassium decreases blood pressure (BP) but can also stimulate aldosterone production2. However, the magnitude of potassium-dependent regulation of aldosterone secretion in humans is not fully characterised and it is not clear whether this is mediated by activation of the renin-angiotensin-aldosterone system (RAAS) as a result of a reduction in BP or other mechanisms.

Aim
To perform a (1) systematic review and meta-analysis of clinical trials assessing effects of potassium on plasma aldosterone and renin in adult individuals alongside a (2) cross-sectional multi-ethnic study to explore the relationship between potassium intake and aldosterone in hypertension.

Methods
(1) This study was carried out in accordance with PRISMA guidelines3. The full protocol can be found on the PROSPERO database. (2) Self-defined black or white hypertensives were recruited from the hypertension outpatient clinic at St. Thomas’ Hospital and had aldosterone, renin and a 24-hour urinary potassium collected. The systematic review and meta-analysis on already approved clinical trials and did not require ethnical approval. The cross-sectional study was approved by the local Research Ethics Committee in the UK and written informed consent was obtained from all patients.

Results
6395 articles were retrieved, and 124 full-text articles were assessed for eligibility. 36 met the prespecified inclusion/exclusion criteria. Potassium supplementation caused a significant decrease in systolic BP (- 3.69 mmHg [-4.91, -2.46], P&lt;0.001) and increase in serum potassium (+0.37 [0.23, 0.52] mmol/L, P&lt;0.001). There was an increase in plasma aldosterone (standardised difference 0.414 [0.291, 0.537], P&lt;0.001) but no effect on plasma renin activity (+0.033 [-0.07, 0.14], P=0.538]. Meta-regression showed a significant positive correlation between change in plasma aldosterone and change in serum potassium (P&lt;0.001). (2) In 469 subjects (72% black), there was a positive association between the measured 24-hour potassium excretion and aldosterone in black (β = 0.200, P = 0.014) but not in white individuals (P = 0.531).

Discussion/Conclusion
Potassium supplementation increases plasma aldosterone but not renin. The increase in aldosterone correlates with the raise in serum potassium. In subjects with hypertension, potassium intake is related with aldosterone concentration only in black subjects. Overall, the data supports a RAAS-independent potassium regulation of aldosterone which could be particularly relevant in African origin subjects. Limitations: 1. the systematic review results could not be stratified by ethnicity because most of the studies were performed in Caucasian subjects, 2. Use of background therapy in some studies, variable doses of potassium supplementation and duration of supplementation.

References
1. Filippou CD, Tsioufis CP, Thomopoulos CG, Mihas CC, Dimitriadis KS, Sotiropoulou LI, Chrysochoou CA, Nihoyannopoulos PI, Tousoulis DM. Dietary Approaches to Stop Hypertension (DASH) Diet and Blood Pressure Reduction in Adults with and without Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Adv Nutr. 2020 Sep 1;11(5):1150-1160. doi: 10.1093/advances/nmaa041. PMID: 32330233; PMCID: PMC7490167.
2. Kotchen TA. Effets du potassium sur la rénine et sur l'aldostérone [Effects of potassium on renin and aldosterone]. Arch Mal Coeur Vaiss. 1984 Apr;77 Spec No:87-91. French. PMID: 6428366.
3. Page M J, McKenzie J E, Bossuyt P M, Boutron I, Hoffmann T C, Mulrow C D et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews BMJ 2021; 372 :n71 doi:10.1136/bmj.n71