Editor:
We have recently reported that dietary potassium correlates negatively with body mass index (BMI) and proteinuria.1 Moreover, high potassium diets have a protective effect against the development of vascular damage induced by salt loading.2 In an effort to dissect the possible mechanisms of the benefits of dietary potassium, we studied the relationship between daily potassium intake and several markers of interest to cardiovascular disease and hypertension.
We performed analysis on the baseline data of the National Institute of Health‐funded Modification of Diet in Renal Disease (MDRD) study. We performed bivariate correlation (Pearson) between dietary potassium (food only) intake and BUN‐to‐creatinine ratio (BUN:Cr), serum calcium (mg/dL), hematocrit (%), hemoglobin A1C (%), serum uric acid (mg/dL), and stroke volume (SV) estimated according to a validated equation using noninvasive parameters.3 Our results revealed a significant positive correlation between daily potassium intake and BUN:Cr, hematocrit, and serum calcium and significant negative correlation with SV, serum uric acid, and hemoglobin A1C. The descriptive statistics of the variables studied, and bivariate correlations with dietary potassium are shown in Table.
Table 1.
Descriptive statistics and correlations
| Variables | N | Minimum | Maximum | Mean | Std. deviation | Pearson correlation with dietary K | P |
|---|---|---|---|---|---|---|---|
| Diet potassium, food only (meq/24 h) | 5338 | 9.3 | 139.6 | 37.4 | 13.1 | ||
| Stroke volume | 2854 | 15.3 | 101.4 | 41.2 | 9.2 | −0.038 | .04 |
| BUN/Cr | 2846 | 5.8 | 61.3 | 15.2 | 4.5 | 0.131 | <.001 |
| Serum uric acid (mg/dL) | 1106 | 1.7 | 17.4 | 7.6 | 1.7 | −0.074 | .01 |
| Calcium (mg/dL) | 2827 | 5.9 | 11.9 | 9.1 | 0.5 | 0.052 | .006 |
| Hematocrit (%) | 2777 | 19.0 | 60.0 | 39.0 | 5.6 | 0.074 | <.001 |
| Hemoglobin A1c (%) | 1093 | 3.8 | 15.0 | 5.7 | 0.9 | −0.069 | .02 |
The statistical associations of dietary potassium intake with SV, BUN:Cr, serum calcium, and HCT are similar to those of thiazide diuretics. These similarities can be explained by the effect of orally ingested potassium on an ill‐defined gastrointestinal sensor that leads through a feed‐forward mechanism to dephosphorylation of the sodium‐chloride cotransporter in the distal convoluted tubules. This effect is equivalent to the effect of thiazide diuretics and explains the antihypertensive property of dietary potassium.4 On the other hand, effects of dietary potassium on uric acid and hemoglobin A1C are opposite to what is expected from thiazide diuretics. Production of uric acid, the end product of xanthine metabolism in humans, yields an equimolar amount of superoxide. Experimentally, a high‐potassium diet was shown to have a potent protective effect on left ventricular active relaxation independent of blood pressure, partly through the inhibition of cardiac NADPH oxidase activity.5 In another study, the antihypertensive effect of dietary potassium was accompanied by sympathetic nerve inhibition in salt‐sensitive hypertension, a marker of insulin resistance.6 Renalase, a monoamine oxidase in the blood that is primarily secreted by the kidneys can metabolize catecholamines and regulate sympathetic activity. Renalase mRNA and protein levels increased along with decreased catecholamine levels in plasma and led to a decrease in blood pressure in salt‐sensitive rats treated with high salt/potassium intake, compared with that of the high salt intake salt‐sensitive control rats.7 Moreover, reactive oxygen species are a critical mediator of the Na‐K‐ATPase pump signaling, and their generation can be attenuated by potassium transit into the cells.8 Taking into consideration the type of the dataset analyzed and the cross‐sectional nature of the analysis, our results cannot be expanded beyond a correlation, but when taken together with other existing evidence from animal and human experiments, it is reasonable to conclude that the protective effects of a high potassium diet can be explained by its antihypertensive and antioxidant properties.
CONFLICT OF INTEREST
The authors report no conflicts of interest to disclose.
ACKNOWLEDGMENTS
The MDRD study was conducted by the MDRD Investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The data from the MDRD reported here were supplied by the NIDDK Central Repositories. This manuscript was not prepared in collaboration with Investigators of the MDRD study and does not necessarily reflect the opinions or views of the MDRD study, the NIDDK Central Repositories, or the NIDDK.
REFERENCES
- 1. Santhanam P, Shapiro JI, Khitan Z. Association between dietary potassium, body mass index, and proteinuria in normotensive and hypertensive individuals: results from the modification of diet in renal disease study baseline data. J Clin Hypertens (Greenwich). 2017;19:611‐612. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Kido M, Ando K, Onozato ML, et al. Protective effect of dietary potassium against vascular injury in salt‐sensitive hypertension. Hypertension. 2008;51:225‐231. [DOI] [PubMed] [Google Scholar]
- 3. Webb WR, Moulder PV, Harrison LH, Broussard ML. Simple method for evaluating cardiac output. J La State Med Soc. 2009;161:287‐289. [PubMed] [Google Scholar]
- 4. Sorensen MV, Grossmann S, Roesinger M, et al. Rapid dephosphorylation of the renal sodium chloride cotransporter in response to oral potassium intake in mice. Kidney Int. 2013;83:811‐824. [DOI] [PubMed] [Google Scholar]
- 5. Matsui H, Shimosawa T, Uetake Y, et al. Protective effect of potassium against the hypertensive cardiac dysfunction: association with reactive oxygen species reduction. Hypertension. 2006;48:225‐231. [DOI] [PubMed] [Google Scholar]
- 6. Ando K, Matsui H, Fujita M, Fujita T. Protective effect of dietary potassium against cardiovascular damage in salt‐sensitive hypertension: possible role of its antioxidant action. Curr Vasc Pharmacol. 2010;8:59‐63. [DOI] [PubMed] [Google Scholar]
- 7. Zheng WL, Wang J, Mu JJ, et al. Effects of salt intake and potassium supplementation on renalase expression in the kidneys of Dahl salt‐sensitive rats. Exp Biol Med (Maywood). 2016;241:382‐386. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Yan Y, Shapiro AP, Haller S, et al. Involvement of reactive oxygen species in a feed‐forward mechanism of Na/K‐ATPase‐mediated signaling transduction. J Biol Chem. 2013;288:34249‐34258. [DOI] [PMC free article] [PubMed] [Google Scholar]