Correspondence

Mineral Balance in Postmenopausal Women Treated With Potassium Bicarbonate

N Engl J Med 1994; 331:1312-1313November 10, 1994

Article

To the Editor:

Sebastian and colleagues (June 23 issue)1 report that the administration of potassium bicarbonate reduced net acid and calcium excretion and had beneficial effects on measures of bone turnover in postmenopausal women. They suggest that the “long-term administration of potassium bicarbonate may therefore be effective in preventing and treating postmenopausal osteoporosis.” It is questionable whether the results of this study are relevant to the vast majority of women.

The protein content of the women's daily diet (96 g per 60 kg of body weight) was considerably higher than that consumed by most women. According to data collected by the National Center for Health Statistics in the first National Health and Nutrition Examination Survey (1976 through 1980),2 the mean protein intake of women 55 to 64 years of age in the United States was 55 g per day and the 90th and 95th percentile values were 90 and 107 g per day, respectively. Thus, with less than 10 percent of the postmenopausal women in the United States consuming the large amount of protein given in the study by Sebastian et al., the generalizability of their findings is open to question.

Raising the dietary protein intake is known to increase urinary calcium excretion and worsen calcium balance.3 For example, in an analysis of 16 published studies involving 154 adults, Kerstetter and Allen4 calculated that in persons eating less than 200 g of protein daily, the relation between protein intake and urinary calcium excretion was linear, such that for each 50-g increment in daily protein intake an extra 60 mg of calcium was excreted in the urine. Thus, if the usual dietary protein intake of the women studied by Sebastian et al. was similar to the U.S. average for this age group,2 the mean ( ±SD) reduction in urinary calcium excretion reported (-64 ±19 mg per day per 60 kg) during supplementation with potassium bicarbonate approximates the increase in calcium excretion induced by the consumption of the excess protein during the study.

Therefore, potassium bicarbonate supplementation may have less efficacy in the majority of postmenopausal women, who have lower protein intakes and endogenous acid loads than the women in the study. Until a study of women given smaller amounts of protein is conducted, the suggestion that alkali supplementation be used to prevent or treat osteoporosis in postmenopausal women is premature.

Richard J. Wood, Ph.D.
Tufts University, Boston, MA 02111

4 References

1. 1

   Sebastian A, Harris ST, Ottaway JH, Todd KM, Morris RC Jr. Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. N Engl J Med 1994;330:1776-1781
   Full Text | Web of Science | Medline

2. 2

   National Center for Health Statistics, Carroll MD, Abraham S, Dresser CM. Dietary intake source data: United States, 1976-80. Vital and health statistics. Series 11. No. 231. Washington, D.C.: Government Printing Office, 1983:14. (DHHS publication no. (PHS) 83-1681.)
   

3. 3

   Allen LH, Wood RJ. Calcium and phosphorus. In: Shils ME, Olson JA, Shike M, eds. Modern nutrition in health and disease. 8th ed. Vol. 1. Philadelphia: Lea & Febiger, 1994:147.
   

4. 4

   Kerstetter JE, Allen LH. Dietary protein increases urinary calcium. J Nutr 1989;120:134-136
   Web of Science

Author/Editor Response

The authors reply:

To the Editor: Dr. Wood is skeptical that potassium bicarbonate will have a long-term beneficial effect on bone mass because the dietary intake of protein in the women we studied was at the high end of the normal range for free-living subjects. The daily intake of protein was 96 g per 60 kg of body weight (62 percent animal and 38 percent vegetable protein), with 41 percent of the total protein intake coming from protein-enriched bread formulated according to the recipe of Lutz.1 Clearly, lower intakes of protein would generate lower amounts of acid. The calcium-wasting and bone-wasting effects of protein-derived acid, however, do not abruptly commence at the high end of the normal range of protein intake. Rather, the magnitude of hypercalciuria induced by dietary protein intake, like the incidence of hip fracture and the decrease in bone mineral density, is a continuous function of the amount of protein ingested over a broad range of intake by free-living subjects.2-5 As Heaney puts it, “The [calciuric] effect extends across the full range of protein intakes, from deficient to surfeit, and is not found only with `excess' protein intake.”2 Even with intakes of protein in the middle of the normal range, women are at risk for a negative calcium balance; the degree depends on such factors as calcium intake, estrogen status, and the source of dietary protein (animal or vegetable).

Potassium bicarbonate is a potent hypocalciuric agent, even when protein intake is not high. Specifically, we studied six normal men eating a whole-food diet containing 48 g of protein per day per 60 kg (unpublished data). They received 90 to 100 mmol of potassium bicarbonate per day for eight days after a base-line period of eight days (Figure 1Figure 1Effect of Oral Administration of Potassium Bicarbonate (KHCO₃) on Urinary Calcium Excretion in Normal Men Eating a Whole-Food Diet Containing an Amount of Protein in the Middle of the Normal Range (48 g of Protein/Day/60 kg).). Within 48 hours after the initiation of potassium bicarbonate, urinary calcium excretion decreased by about one third. The mean base-line excretion of net acid (37 meq per day) and calcium (122 mg [3.1 mmol] per day) was about half that of the postmenopausal women in our study. Accordingly, substantially lower dietary intakes of protein than those of the women in our study would not preclude a beneficial effect of potassium bicarbonate on bone, if the hypocalciuric effect of potassium bicarbonate persists during long-term administration.

Anthony Sebastian, M.D.
R. Curtis Morris, Jr., M.D.
University of California, San Francisco, San Francisco, CA 94143

5 References

1. 1

   Lutz J. Calcium balance and acid-base status of women as affected by increased protein intake and by sodium bicarbonate ingestion. Am J Clin Nutr 1984;39:281-288
   Web of Science | Medline

2. 2

   Heaney RP. Protein intake and the calcium economy. J Am Diet Assoc 1993;93:1259-1260
   CrossRef | Web of Science | Medline

3. 3

   Abelow BJ, Holford TR, Insogna KL. Cross-cultural association between dietary animal protein and hip fracture: a hypothesis. Calcif Tissue Int 1992;50:14-18
   CrossRef | Web of Science | Medline

4. 4

   Hu J-F, Zhao X-H, Parpia B, Campbell TC. Dietary intakes and urinary excretion of calcium and acids: a cross-sectional study of women in China. Am J Clin Nutr 1993;58:398-406
   Web of Science | Medline

5. 5

   Hu J-F, Zhao X-H, Jia J-B, Parpia B, Campbell TC. Dietary calcium and bone density among middle-aged and elderly women in China. Am J Clin Nutr 1993;58:219-227
   Web of Science | Medline