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Abstract: TH-PO0389

Metabolomics of Oral Bicarbonate Supplementation

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

  • Petrovic, Snezana, Campbell University School of Osteopathic Medicine, Lillington, North Carolina, United States
  • Motyka, Thomas M, Campbell University School of Osteopathic Medicine, Lillington, North Carolina, United States
  • Anderson, Andrea Marie, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
  • Thakkar, Vandan, Campbell University School of Osteopathic Medicine, Lillington, North Carolina, United States
  • Renfro, Jonathan, Campbell University School of Osteopathic Medicine, Lillington, North Carolina, United States
  • Beavers, Kristen, Wake Forest University, Winston-Salem, North Carolina, United States
  • Leng, Xiaoyan, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
  • Wesson, Donald E., Dell Seton Medical Center at The University of Texas, Austin, Texas, United States
  • Kritchevsky, Stephen B., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
Background

Preliminary results (FASEB J33(S1), 2019) from our double-blind, placebo-controlled, randomized pilot trial designed to ameliorate high dietary acid load with oral bicarbonate supplementation (0.3mEq/kg/d) in community-dwelling older adults (73±5 years) with high net endogenous acid production (NEAP=76±27mEq/d), good physical (short physical performance battery=10.5±1.5) and kidney function (eGFR=81±19ml/min/1.73m2), indicated that the intervention was safe and increased blood bicarbonate significantly (Δ=1.3±2 mEq/L in bicarb vs. placebo).

Methods

A broad-spectrum metabolomics analysis was performed by Metabolon, (Morrisville, NC) on 136 serum samples from all participants that completed the trial collected at baseline vs. 6-month visit in bicarb (n=33) vs. placebo (n=35) groups. Analyses compared metabolite changes between groups over time, with adjustment for multiple comparisons.

Results

Although principal component analysis showed no global separation between groups, individual groups of biochemicals changed. Comparing bicarb vs. placebo at baseline vs. 6 months, we found that citrate increased significantly, consistent with reduced body acid content, while 2 uremic toxins (p-cresol sulfate and 3-indoxyl sulfate) decreased with borderline significance. The highest number of significantly changed metabolites was identified in the bicarb baseline vs. 6 months: 57 metabolites increased, and 78 metabolites decreased, including a small decrease in serum creatinine. Uremic toxins, phenylacetyl glutamate (PAG), S-adenosylhomocysteine (SAH), CMPF (3-carboxy-4-methyl-5-propyl-2-furanpropanoate), and 3-carboxy-4-methyl-5-pentyl-2-furanpropionate (3-CMPFP) decreased as did anti-inflammatory metabolites such as several endocannabinoids and methylhistidines. Methylation of histidine is muscle-specific and may reflect a decrease in muscle protein breakdown. Of 555 detected lipids, >40 changed (20 significantly), including phospholipids, plasmalogens and sphingomyelins.

Conclusion

Decreasing high dietary acid load with oral bicarbonate for 6 months is associated with favorable changes in serum citrate, creatinine, uremic toxins, inflammation markers, and a surprisingly high number of lipids. The changes provide biologic clues about modified metabolic pathways and need to be replicated with targeted metabolomics.

Funding

  • Other NIH Support

Digital Object Identifier (DOI)