Effects of potassium bicarbonate supplements on circulating microRNA expression

Authors: MARGOLIS, LEE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DAWSON-HUGHES, BESS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; RIVAS, DONATO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; EZZYAT, YASSINE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; CEGLIA, LISA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of the Endocrine Society
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/8/2017
Publication Date: 6/14/2017
Citation: Margolis, L.M., Dawson-Hughes, B., Rivas, D.A., Ezzyat, Y., Fielding, R.A., Ceglia, L. 2017. Effects of potassium bicarbonate supplements on circulating microRNA expression. Journal of the Endocrine Society. https://doi.org/10.1210/js.2017-00106.

Interpretive Summary: Acid-producing diets in combination with age-related declines in renal function induce a mild but progressive metabolic acidosis, or acid/base imbalance, that is thought to contribute to the development of osteoporosis and sarcopenia in older adults. A number of intervention studies have shown that supplementation with alkaline salts, potassium bicarbonate or citrate, in an amount that neutralizes the acid load of the diet significantly reduces bone resorption biomarkers with less consistent effects on bone formation biomarkers. In studies examining skeletal muscle markers, alkaline supplementation has not shown consistently favorable effects across studies. Small non-coding RNAs, known as microRNAs, have recently been identified to have important functional roles in regulating key processes determining bone and skeletal muscle mass. Being membrane-bound, circulating microRNAs are stable and reproducible analytes that reflect the underlying physiological state of donor tissue, thus offering a unique perspective as noninvasive biomarkers. The objective of this pilot study was to examine whether a subset of participants consuming an alkaline salt supplement, oral potassium bicarbonate or matched placebo for 84-days altered circulating microRNA expression profiles. Furthermore, this investigation sought to determine the association between changes in the expression of these musculoskeletal-associated circulating microRNAs and changes in established indices of bone and muscle turnover by treatment group. Our study found that reducing renal acid load with potassium bicarbonate supplements was associated with increased expression of two circulating microRNAs that are involved in bone formation. Furthermore, increases in these microRNAs were inversely associated with bone resorption markers consistent with potential beneficial effects on bone in older adults. However, the broader significance of circulating microRNAs as musculoskeletal biomarkers is still under investigation, and larger studies are needed to verify these preliminary results.

Technical Abstract: Several studies suggest that neutralizing the acid load in the diet with alkali has favorable effects on intermediate markers of musculoskeletal health. We examined whether alkali supplementation with potassium bicarbonate (KHCO3; 81 mmol/d, n=12) vs. placebo (n=12) for 84 days altered serum microRNAs - potential biomarkers associated with innumerable biological processes including bone and muscle metabolism. Serum microRNAs, urinary net acid excretion (UNAE), N-telopeptide (UNTX), calcium (UCa), nitrogen (UN), GFR, serum P1NP, serum IGF-1, and serum IGF-BP3 were measured at baseline and day 84. Baseline characteristics and measurements were similar in the two treatment groups. Eighty-four-day changes in UNAE differed by group (KHCO3=-47+/-9 mmol; Placebo=-5+/-5 mmol; P<0.01). KHCO3 significantly reduced UNTX, UCa, and serum P1NP, but did not affect UN, serum IGF-1, or IGF-BP3 levels compared to placebo over 84 days. Fold change in serum cmiRNA-133b differed significantly by group (KHCO3=2.26+/-0.85; Placebo=-1.23+/-0.69; P<0.01); there was a similar trend in c-miRNA-21-5p. Fold changes in c-miRNA-133b and 21-5p were inversely associated with changes in UNAE and UNTX; fold change in c-miRNA-21-5p was inversely associated with change in UCa with a similar trend with c-miRNA-133b. In summary, reducing renal acid load with KHCO3 was associated with increased expression of c-miRNAs-133b and 21-5p. Furthermore, increases in cmiRNA-133b and 21-5p were inversely associated with bone resorption markers, UNTX and UCa, consistent with potential beneficial effects on bone in older adults. However, the broader significance of c-miRNAs as musculoskeletal biomarkers is still under investigation and larger studies are needed to verify these preliminary results.