With aging, men and women develop a mild and progressive metabolic acidosis. This occurs as a result of declining renal function and ingestion of acid-producing diets. There is extensive evidence that severe metabolic acidosis causes bone and muscle loss, but the impact of the chronic, mild acidosis on bone and muscle in older individuals has not been established. In our recently completed NIH-funded trial in 171 older men and women, alkalinizing the diet with a bicarbonate supplement daily for 3 months significantly reduced urinary excretion of N-telopeptide (NTX), a marker of bone resorption, and urinary nitrogen, a marker of muscle wasting. Moreover, bicarbonate supplements significantly improved muscle performance in the women. These and other data support a potential role for bicarbonate as a means of reducing the musculoskeletal declines that lead to extensive morbidity and mortality in the elderly. Before proceeding to a long-term bicarbonate intervention study, however, it is important to identify the dose of bicarbonate most likely to be optimal and to characterize the subjects who benefit most from it. The proposed dose-finding study will extend our previous work in this area by evaluating the effects of placebo and two doses of bicarbonate on urinary NTX and nitrogen excretion and on lower extremity performance. The lowest dose we plan to test is similar to the dose shown in our recent trial to be effective. The proposed study is a double blind, randomized, placebo-controlled, parallel-group trial in which 138 men and 138 women, age 60 and older, will take potassium bicarbonate in doses of 1.0 or 1.5 mmol/kg of body weight or placebo daily for three months. Changes in urinary excretion of NTX and nitrogen and in selected measures of lower extremity performance will be compared across the three groups. The safety and tolerability of the interventions will also be evaluated. This investigation should provide needed information on the appropriate dosing regimen and on the study population that should be enrolled in a future long-term bicarbonate intervention trial to assess the long-term effects of this simple, low cost intervention on important clinical outcomes including rates of loss in bone and muscle mass, falls, and fractures.

Public Health Relevance

Despite recognition that mild metabolic acidosis contributes to muscle and bone wasting, most older men and women consume diets which aggravate the acidosis. This proposal describes a study designed to identify the dose of an alkali supplement likely to be needed to reverse the acidosis process. This dose of alkali can then be tested for its long-term effects on rates of bone and muscle loss, on falls, and fractures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR060261-04
Application #
8706797
Study Section
Aging Systems and Geriatrics Study Section (ASG)
Program Officer
Chen, Faye H
Project Start
2011-09-01
Project End
2015-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Tufts University
Department
Nutrition
Type
Organized Research Units
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02111
Ceglia, L; Dawson-Hughes, B (2017) Increasing alkali supplementation decreases urinary nitrogen excretion when adjusted for same day nitrogen intake. Osteoporos Int 28:3355-3359
Shea, M K; Gilhooly, C H; Dawson-Hughes, B (2017) Food groups associated with measured net acid excretion in community-dwelling older adults. Eur J Clin Nutr 71:420-424
Margolis, Lee M; Dawson-Hughes, Bess; Rivas, Donato A et al. (2017) Effects of Potassium Bicarbonate Supplements on Circulating microRNA Expression. J Endocr Soc 1:1015-1026
Dawson-Hughes, Bess; Harris, Susan S; Palermo, Nancy J et al. (2015) Potassium Bicarbonate Supplementation Lowers Bone Turnover and Calcium Excretion in Older Men and Women: A Randomized Dose-Finding Trial. J Bone Miner Res 30:2103-11