In patients with kidney disease receiving hemodialysis, metabolic acidosis is closely tied to muscle pathology and is known to exacerbate age-related loss of muscle mass and function. To a lesser extent, the ‘‘Western’’ diet is thought to contribute to mild (sub-clinical) metabolic acidosis via the supply of acid precursors from foods [1], but the clinical significance to chronic age-related muscle degeneration has received little attention. This may partly be due to equivocal data on the benefits of neutralizing diet-induced metabolic acidosis for improving muscle-related outcomes in patients without kidney disease [2]. Despite limited data, acidosis has been shown to stimulate muscle proteolysis and is associated with negative functional outcomes including reduced peak torque and lower gait speed [3]. This is important to note because aged adults are less able to excrete excess H ions and are more prone to develop mild, but slowly increasing metabolic acidosis that may be exacerbated by a ‘‘Western’’ diet [1]. Furthermore, approximately one out of four adults older than 50 years of age have low serum bicarbonate levels to neutralize an acidogenic diet. Because of these factors, recommendations for future work include examining the effects of alkali therapy on functional outcomes, nitrogen balance, strength and other relevant measures of physical function, in aged healthy adults [3]. Vitamin D status (measured as 25(OH)D) is also garnering interest as a player in preserving skeletal muscle mass and function in aging. Although, the study of vitamin D deficiency and repletion, in relation to muscle metabolic function in aging is relatively new, vitamin D deficiency has already been associated with several negative muscle outcomes including muscle degeneration with fat infiltration [4]. Loss of muscle fiber size and reduction in muscle protein synthesis have also been documented and is thought to be clinically significant since vitamin D deficiency is considered as a worldwide epidemic [5]. In this issue of Endocrine, Ceglia et al. [6] investigated the interactions between potassium bicarbonate and vitamin D supplementation to shed light on the underlying mechanisms associated with muscle atrophy, conservation, and fiber morphology in male rats. The author’s rationale for examining the vitamin D/bicarbonate interaction was based on research from the 1970s citing that depletion of vitamin D resulted in metabolic acidosis, whereas repletion resulted in a metabolic alkalosis by changes in renal tubule bicarbonate reabsorption. An additional cited study provided support that acute metabolic acidosis resulted in suppression of 1-alpha hydroxylase activity, collectively suggesting that the alterations in either vitamin D status or acid–base balance may affect the other and, thus, have detrimental impact on muscle tissue [6]. Ceglia et al. [6] found that potassium bicarbonate supplementation resulted in 35 % lower urinary nitrogen to creatinine (UNi/Cr) ratio independent of vitamin D status. In vitamin D deficient rats, potassium bicarbonate resulted in 28 % increase in UNi/Cr compared to rats with normal vitamin D levels, but the findings did not reach the statistical significance. Furthermore, in rats experiencing metabolic acidosis, higher vitamin D status seemed to work synergistically with bicarbonate to potentiate Akt activation, a protein kinase involved in several anabolic pathways. As a result of their findings, the authors suggested that longer more comprehensive investigation is required to advance and confirm the impact of a dietary intervention on ubiquitin–proteasome pathway at different pathway time points and to fully D. Travis Thomas (&) Division of Clinical Nutrition, University of Kentucky, Lexington, KY, USA e-mail: david.t.thomas@uky.edu
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Oct 9, 2014
S A Bayol + 2
Open Access