Dietary Reference Intakes for Sodium and Potassium (2019) / Chapter Skim
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6 Potassium: Dietary Reference Intakes Based on Chronic Disease
6 Potassium: Dietary Reference Intakes Based on Chronic Disease
Pages 141-182
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From page 141... ...
. In its application of the recommendations in the Guiding Principles for Developing Dietary Reference Intakes Based on Chronic Disease (Guiding Principles Report)
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From page 142... ...
, the committee considered the use of evidence from different study designs in its derivation of the potassium CDRRs. As compared to randomized controlled trials, observational studies are inherently weaker for establishing causal relationships and begin at a lower strength of evidence rating in the Grading of Recommendations Assessment, Development and Evalua TABLE 6-1 Potential Chronic Disease Indicators Reviewed for a Causal Relationship with Potassium Intake, in Order of Presentation 2005 AHRQ Committee's DRI Systematic Supplemental Indicator Report Review Literature Search All-cause mortality X Cardiovascular disease X Coronary heart disease X X Myocardial infarction X Stroke X X Blood pressure X X Kidney stones X X Chronic kidney disease X Osteoporosis and related indicators Xa X Type 2 diabetes, glycemic control, and X insulin sensitivity NOTE: AHRQ = Agency for Healthcare Research and Quality; DRI = Dietary Reference Intake.
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From page 143... ...
Committee-Conducted Meta-Analyses The committee rated the AHRQ Systematic Review as being of moderate quality, as guided by AMSTAR 2 criteria (for additional details, see Appendix C) .1 One of the domains that the AHRQ Systematic Review did not adequately cover related to investigation and explanation of the causes of heterogeneity in the results of meta-analyses.
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From page 144... ...
Evidence presented in the 2005 DRI Report The relationship between potassium intake and all-cause mortality was not reviewed in the 2005 DRI Report. Evidence provided in the AHRQ Systematic Review No randomized controlled trials meeting the AHRQ Systematic Review inclusion criteria evaluated the independent effect of potassium intake on all-cause mortality.
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From page 145... ...
The AHRQ Systematic Review characterized the evidence on the modifying effect of chronic disease on the association between potassium intake and all-cause mortality as insufficient. Committee's synthesis of the evidence The lack of randomized controlled trials in which potassium intake was the only component of the diet modulated limits the committee's ability to determine if potassium intake has an independent effect on all-cause mortality risk.
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From page 146... ...
Evidence provided in the AHRQ Systematic Review No randomized controlled trials meeting the AHRQ Systematic Review inclusion criteria evaluated the independent effect of potassium intake on cardiovascular disease mortality and morbidity. Observational studies that assessed the association between urinary potassium excretion and composite cardiovascular disease outcomes among generally healthy adult populations mostly reported nonstatistically significant relationships (Cook et al., 2009; Kieneker et al., 2016b; O'Donnell et al., 2014)
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From page 147... ...
The AHRQ Systematic Review characterized this evidence as insufficient to identify an association between potassium intake and cardiovascular disease mortality. Committee's synthesis of the evidence he lack of randomized controlled T trials in which potassium intake is the only component of the diet modulated limits the committee's ability to determine if potassium intake has an independent effect on the risk of cardiovascular disease mortality or combined cardiovascular outcomes.
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From page 148... ...
Evidence for coronary heart disease was not used to determine, support, or justify the potassium reference values established in the 2005 DRI Report. Evidence provided in the AHRQ Systematic Review No randomized controlled trials meeting the AHRQ Systematic Review inclusion criteria evaluated the independent effect of potassium intake on coronary heart disease morbidity and mortality.
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From page 149... ...
The AHRQ Systematic Review characterized the evidence as insufficient to be able to identify an association between potassium intake and coronary heart disease mortality. Committee's synthesis of the evidence The lack of randomized controlled trials in which potassium intake is the only component of the diet modulated limits the committee's ability to determine if potassium intake has an independent effect on the risk of coronary heart disease mortality or combined coronary heart disease morbidity and mortality.
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From page 150... ...
Evidence provided in the AHRQ Systematic Review No randomized controlled trials meeting the AHRQ Systematic Review inclusion criteria evaluated the independent effect of potassium intake on myocardial infarction. Two observational studies assessed the relationship between potassium intake and myocardial infarction in a cohort of generally healthy adults (Geleijnse et al., 2007; O'Donnell et al., 2014)
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From page 151... ...
Evidence provided in the AHRQ Systematic Review No randomized controlled trials met the AHRQ Systematic Review inclusion criteria for this outcome. Fifteen observational studies assessing the association between potassium intake and stroke were included.
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From page 152... ...
The AHRQ Systematic Review characterized the statistical significance of the associations between potassium intake and stroke as mixed among studies that used dietary intake assessment methodologies. The relationship between potassium intake and stroke was also assessed among population groups characterized by a chronic disease or condition.
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From page 153... ...
Committee's synthesis of the evidence The lack of randomized controlled trials in which potassium intake is the only component of the diet modulated limits the committee's ability to determine if potassium intake has an independent effect on stroke. The association between potassium intake and risk of stroke did not reach statistical significance in many of the observational studies included in the AHRQ Systematic Review.
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From page 154... ...
had a significant influence on the estimate. A 2014 update of this systematic review added three additional analyses, including one analysis in which the potassium exposure was based on a baseline spot urine sample (D'Elia et al., 2014)
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From page 155... ...
Given that the evidence on the relationship is entirely derived from analyses of observational data, and therefore limits the committee's ability to determine the independent effect of potassium, the strength of evidence on the causal relationship between potassium intake and stroke does not qualify for a moderate rating. The committee is in agreement with the AHRQ Systematic Review assessment that there is insufficient evidence on the association between potassium intake and stroke.
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From page 156... ...
There were no key questions about salt-sensitive blood pressure changes. Furthermore, the provision of potassium was only 3 weeks in length, which is shorter than the inclusion criteria for the AHRQ Systematic Review.
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From page 157... ...
The AHRQ Systematic Review identified 10 parallel randomized controlled trials and 8 crossover trials that examined the effect of potassium supplements, as compared to placebo. A random-effects meta-analysis across the 18 trials resulted in a mean difference in systolic blood pressure of –6.43 mm Hg ([95% CI: –11.06, –1.80]
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From page 158... ...
Children and adolescents One parallel randomized controlled trial and one controlled trial assessing the effect of potassium supplementation on blood pressure in children and adolescents met the AHRQ Systematic Review inclusion criteria. In the randomized controlled trial, 210 adolescents (mean: 13 years of age at baseline)
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From page 159... ...
were an apparent outlier, all analyses were repeated without this trial. Updated results for blood pressure Despite some changes in the studies and corrections to individual study effects, the overall results were similar to those reported in the AHRQ Systematic Review; increased potassium intake through potassium supplementation decreased blood pressure.
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From page 160... ...
The AHRQ Systematic Review included potassium bicarbonate in its analysis while most of the other studies included potassium chloride. The AHRQ Systematic Review reported a difference for ambulatory blood pressure of 0/+1 mm Hg.
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From page 161... ...
NOTES: Studies are listed by the last name of the first author and year of publication. CI = confidence interval; I2 = statistic that describes the percent of variation across studies due to heterogeneity; K = potassium; K-H = Knapp-Hartung variance estimate; RE = random-effects; SBP = systolic blood pressure; TOHP = Trials of Hypertension Prevention.
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From page 162... ...
The lack of an intake–response relationship with net change in potassium excretion was observed in both those with and without hypertension at baseline. Similar results with respect to eliminating the outlier and separating studies by hypertension status were seen for diastolic blood pressure (see Figure 6-6)
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From page 163... ...
FIGURE 6-4 Meta-regression of trials of potassium supplementation showing the effect of the baseline systolic blood pressure on the systolic blood pressure effect size. NOTE: CI = confidence interval; I2 = statistic that describes the percent of variation across studies due to heterogeneity; SBP = systolic blood pressure.
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From page 164... ...
NOTES: Studies are listed by the last name of the first author and year of publication. CI = confidence interval; I2 = statistic that describes the percent of variation across studies due to heterogeneity; K = potassium; K-H = Knapp-Hartung variance estimate; RE = random-effects; SBP = systolic blood pressure; TOHP = Trials of Hypertension Prevention.
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From page 165... ...
The committee's refinement of the AHRQ Systematic Review was not able to identify an explanation for the observed heterogeneity, and therefore the committee reaffirmed the AHRQ Systematic Review rating of the strength of evidence between increased potassium intake (achieved by potassium supplementation) and decreased blood pressure as moderate.
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From page 166... ...
Without such evidence, the committee is unable to consider blood pressure as a qualified surrogate marker in the context of potassium interventions. Given the lack of an intake–response relationship, and in accordance with guidance in the Guiding Principles Report on use of qualified surrogate markers in establishing DRIs based on chronic disease, the committee did not find the sufficient evidence to use blood pressure as an indicator to establish a potassium CDRR.
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From page 167... ...
The AHRQ Systematic Review concluded that there was insufficient evidence to draw conclusions about the effect of higher potassium intake on the risk for kidney stones. Two observational studies, which included analyses of four cohorts, met the inclusion criteria for the AHRQ Systematic Review.
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From page 168... ...
Chronic kidney disease was not reviewed in the 2005 DRI Report as a potential indicator for establishing a potassium DRI value. Evidence provided in the AHRQ Systematic Review No randomized controlled trials meeting the AHRQ Systematic Review inclusion criteria evaluated the independent effect of potassium intake on the risk of chronic kidney disease.
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From page 169... ...
Five cross-sectional studies and one longitudinal study provided evidence that potassium intake and/or urinary potassium excretion was positively associated with bone mineral density. The observational evidence for the relationship between potassium intake and bone loss was not used as the primary data to establish the potassium AI in the 2005 DRI Report, but was described as being supporting evidence.
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From page 170... ...
Bone mineral density Three randomized controlled trials meeting the inclusion criteria evaluated the effect of potassium intake on bone mineral density. A 2-year placebo-controlled trial among 203 postmenopausal women reported no statistically significant differences in lumbar spine or total hip bone mineral density among participants receiving potassium citrate in high or low dose (Macdonald et al., 2008)
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From page 171... ...
Three observational studies on the association between potassium intake and bone mineral density were identified. In a study of 266 postmenopausal women, those in the highest quartile of urinary potassium excretion had higher total hip bone mineral density and total bone mineral density at year 5, as compared to those in the lowest quartile of potassium excretion (Zhu et al., 2009)
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From page 172... ...
Type 2 Diabetes, Glycemic Control, and Insulin Sensitivity Evidence presented in the 2005 DRI Report The 2005 DRI Report did not review evidence on the relationship between potassium intake and type 2 diabetes, glycemic control, or insulin sensitivity. Evidence provided in the AHRQ Systematic Review The AHRQ Systematic Review included individuals with type 2 diabetes as a subgroup of consideration throughout the key questions.
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From page 173... ...
However, the meta-analysis also showed a considerable amount of heterogeneity across trials. In its refinement of the analysis in the AHRQ Systematic Review, the committee explored multiple potential sources of heterogeneity, including the removal of an outlier study and consideration of an intake–response relationship, but none explained more than a small portion of the observed heterogeneity.
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From page 174... ...
The strength of evidence to support a causal relationship between increased potassium intake and related chronic disease outcomes, such as cardiovascular disease outcomes or hypertension, was graded as low or insufficient. Without evidence on the relationship between increases in potassium intake and risk of chronic disease outcomes, blood pressure cannot be considered a qualified surrogate marker in the context of potassium interventions.
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From page 175... ...
2010. Increased potassium intake from fruit and vegetables or supplements does not lower blood pressure or im prove vascular function in UK men and women with early hypertension: A randomised controlled trial.
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2014. A randomised controlled trial evaluating the effect of potassium supplementation on vascular func tion and the renin-angiotensin-aldosterone system.
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2001. Effect of potassium supplementa tion on blood pressure in Chinese: A randomized, placebo-controlled trial.
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2012. Effect of potassium supplementation on renal tubular function, ambulatory blood pressure and pulse wave velocity in healthy humans.
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2003. The effect of low-dose potassium supplementation on blood pressure in apparently healthy volunteers.
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2007. The effect of high-calcium and high potassium diet on grade-I hypertension and high normal blood pressure.
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2016. Effects of potassium magnesium citrate supplementation on 24-hour ambulatory blood pressure and oxidative stress marker in prehypertensive and hypertensive subjects.
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