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      Nutritional disturbance in acid–base balance and osteoporosis: a hypothesis that disregards the essential homeostatic role of the kidney

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          Abstract

          The nutritional acid load hypothesis of osteoporosis is reviewed from its historical origin to most recent studies with particular attention to the essential but overlooked role of the kidney in acid–base homeostasis. This hypothesis posits that foods associated with an increased urinary acid excretion are deleterious for the skeleton, leading to osteoporosis and enhanced fragility fracture risk. Conversely, foods generating neutral or alkaline urine would favour bone growth and Ca balance, prevent bone loss and reduce osteoporotic fracture risk. This theory currently influences nutrition research, dietary recommendations and the marketing of alkaline salt products or medications meant to optimise bone health and prevent osteoporosis. It stemmed from classic investigations in patients suffering from chronic kidney diseases (CKD) conducted in the 1960s. Accordingly, in CKD, bone mineral mobilisation would serve as a buffer system to acid accumulation. This interpretation was later questioned on both theoretical and experimental grounds. Notwithstanding this questionable role of bone mineral in systemic acid–base equilibrium, not only in CKD but even more in the absence of renal impairment, it is postulated that, in healthy individuals, foods, particularly those containing animal protein, would induce ‘latent’ acidosis and result, in the long run, in osteoporosis. Thus, a questionable interpretation of data from patients with CKD and the subsequent extrapolation to healthy subjects converted a hypothesis into nutritional recommendations for the prevention of osteoporosis. In a historical perspective, the present review dissects out speculation from experimental facts and emphasises the essential role of the renal tubule in systemic acid–base and Ca homeostasis.

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          Most cited references80

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          Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein.

          F Manz, T Remer (1994)
          The object of this study was to determine whether it is possible to reliably estimate the renal net acid excretion (NAE) produced by adults consuming different amounts of dietary protein. A physiologically based calculation model that corrects for intestinal absorption of minerals and sulfur-containing protein and assumes a rate of urinary excretion of organic acids proportional to body surface area was used to estimate NAE. Urinary excretion of different minerals and NAE was measured during the last 48 h of each of four separate 5-d diet periods in six healthy adults. On the basis of food tables, the four nearly isoenergetic diets (one lacto-vegetarian and one high- and two moderate-protein diets) were estimated to yield the following NAE values: 3.7, 117.5, 62.2, and 102.2 mEq/d, respectively. The analytically determined urinary NAE (24.1 +/- 10.7, 135.5 +/- 16.4, 69.7 +/- 21.4, and 112.6 +/- 10.9 mEq/d) corresponded reasonably well to these estimates, suggesting that the calculation model is appropriate to predict the renal NAE from nutrient intake and anthropometric data.
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            Dietary protein and bone health: a systematic review and meta-analysis.

            There has been a resurgence of interest in the controversial relation between dietary protein and bone health. This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.
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              Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate.

              In normal subjects, a low level of metabolic acidosis and positive acid balance (the production of more acid than is excreted) are typically present and correlate in degree with the amount of endogenous acid produced by the metabolism of foods in ordinary diets abundant in protein. Over a lifetime, the counteraction of retained endogenous acid by base mobilized from the skeleton may contribute to the decrease in bone mass that occurs normally with aging. To test that possibility, we administered potassium bicarbonate to 18 postmenopausal women who were given a constant diet (652 mg [16 mmol] of calcium and 96 g of protein per 60 kg of body weight). The potassium bicarbonate was given orally for 18 days in doses (60 to 120 mmol per day) that nearly completely neutralized the endogenous acid. During the administration of potassium bicarbonate, the calcium and phosphorus balance became less negative or more positive--that is, less was excreted in comparison with the amount ingested (mean [+/- SD] change in calcium balance, +56 +/- 76 mg [1.4 +/- 1.9 mmol] per day per 60 kg; P = 0.009; change in phosphorus balance, +47 +/- 64 mg [1.5 +/- 2.1 mmol] per day per 60 kg; P = 0.007) because of reductions in urinary calcium and phosphorus excretion. The changes in calcium and phosphorus balance were positively correlated (P < 0.001). Serum osteocalcin concentrations increased from 5.5 +/- 2.8 to 6.1 +/- 2.8 ng per milliliter (P < 0.001), and urinary hydroxyproline excretion decreased from 28.9 +/- 12.3 to 26.7 +/- 10.8 mg per day (220 +/- 94 to 204 +/- 82 mumol per day; P = 0.05). Net renal acid excretion decreased from 70.9 +/- 10.1 to 12.8 +/- 21.8 mmol per day, indicating nearly complete neutralization of endogenous acid. In postmenopausal women, the oral administration of potassium bicarbonate at a dose sufficient to neutralize endogenous acid improves calcium and phosphorus balance, reduces bone resorption, and increases the rate of bone formation.
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                Author and article information

                Journal
                Br J Nutr
                Br. J. Nutr
                BJN
                The British Journal of Nutrition
                Cambridge University Press (Cambridge, UK )
                0007-1145
                1475-2662
                14 October 2013
                04 April 2013
                : 110
                : 7
                : 1168-1177
                Affiliations
                [ ]Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine , Rue Gabrielle-Perret-Gentil, CH-1211Geneva 14, Switzerland
                Author notes
                [* ] Corresponding author: Dr Jean-Philippe Bonjour, fax +41 22 38 29 973, email jean-philippe.bonjour@ 123456unige.ch
                Article
                S0007114513000962 00096
                10.1017/S0007114513000962
                3828631
                23551968
                1c4abb30-9861-4e8a-91be-2aca12076a4e
                © The Author 2013

                The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution licence < http://creativecommons.org/licenses/by/3.0/

                History
                : 24 August 2012
                : 22 February 2013
                : 22 February 2013
                Categories
                Review Article

                Nutrition & Dietetics
                nutrition,osteoporosis,acid–base balance,renal proton regulation,urinary calcium

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