Meta‐Analysis of the Effect of the Acid‐Ash Hypothesis of Osteoporosis on Calcium Balance

Tanis R. Fenton  Andrew W. Lyon  Michael Eliasziw  Suzanne C. Tough  David A. Hanley

Abstract

The acid‐ash hypothesis posits that protein and grain foods, with a low potassium intake, produce a diet acid load, net acid excretion (NAE), increased urine calcium, and release of calcium from the skeleton, leading to osteoporosis. The objectives of this meta‐analysis were to assess the effect of changes in NAE, by manipulation of healthy adult subjects' acid‐base intakes, on urine calcium, calcium balance, and a marker of bone metabolism, N‐telopeptides. This meta‐analysis was limited to studies that used superior methodological quality for the study of calcium metabolism. We systematically searched the literature and included studies if subjects were randomized to the interventions and followed the recommendations of the Institute of Medicine's Panel on Calcium and Related Nutrients for calcium studies. Five of 16 studies met the inclusion criteria. The studies altered the amount and/or type of protein. Despite a significant linear relationship between an increase in NAE and urinary calcium (p < 0.0001), there was no relationship between a change of NAE and a change of calcium balance (p = 0.38; power = 94%). There was no relationship between a change of NAE and a change in the marker of bone metabolism, N‐telopeptides (p = 0.95). In conclusion, this meta‐analysis does not support the concept that the calciuria associated with higher NAE reflects a net loss of whole body calcium. There is no evidence from superior quality balance studies that increasing the diet acid load promotes skeletal bone mineral loss or osteoporosis. Changes of urine calcium do not accurately represent calcium balance. Promotion of the “alkaline diet” to prevent calcium loss is not justified.

INTRODUCTION

Osteoporosis has a substantial impact on the quality of life,1 and in some cases, the quantity of life.2 The acid‐ash hypothesis attributes the etiology of osteoporosis to nutritional factors.3-6 This hypothesis states that the modern diet causes osteoporosis through the metabolic production of acid and that the process of buffering this acid requires mobilization of bone mineral, with the resultant calcium lost in the urine.7-10

The acid‐ash hypothesis identifies protein and grain foods as those that cause release of calcium from the skeleton to buffer the acid load from the diet and increase urinary excretion of calcium. According to the hypothesis, this acid load causes gradual loss of skeletal calcium. The hypothesis also suggests fruit and vegetables provide a supply of organic molecules that are metabolized to bicarbonate and therefore protect skeletal mineral.7-10 Specifically, the hypothesis states that food or supplemental sources of anions (referred to as acids), phosphate (PO4−), sulfate (SO4−), chloride (Cl−), and organic acids, reflect dietary acid intake, cause metabolic acidemia, and increase calciuria when consumed in excess, which is detrimental to bone health.4-6 In contrast, food sources or supplements of cations (referred to as alkaline or bases), sodium (Na+), potassium (K+), calcium (Ca2+), and magnesium (Mg2+), are considered under the hypothesis to reflect base intake, decrease calciuria, and exert a protective effect on bone.5, 11 According to the acid‐ash hypothesis, protein5, 7, 12-16 and grain7 foods are detrimental to bone health because of sulfate and phosphate production,7 whereas fruit and vegetables are bone protective because of their potassium‐organic anion content.6, 7, 16

This acid‐ash hypothesis has not been subjected to critical review. Despite no critical review, this hypothesis is promoted to the public as the “alkaline diet” through the internet as a cure to almost any disease.

A meta‐analysis of the literature showed evidence of a linear relationship between urine net acid excretion (NAE) and the quantity of calcium excreted in the urine.17 The estimated excess urine calcium associated with the modern diet is 1.6 mmol/d (66 mg/d) calcium.17 Over a lifetime, this excess calciuria is of sufficient quantity that it could explain the progression of bone mineral loss of osteoporosis17; however, whether this urinary calcium is important for bone health depends on whether the interventions also cause a change of calcium balance.18

It is assumed by the hypothesis that the excess urinary calcium is equal to the loss of bone calcium to the body. Some researchers have proposed that, if intestinal calcium absorption18 and/or endogenous secretion19 compensates for some or all of the increase of urinary calcium, calcium may or may not be lost from bone.

Trials that use calcium balance as an outcome need to be designed to differentiate between changes in calcium retention that are caused by an intervention and those caused by study design. For example, if the calcium intakes of the subjects are altered from their usual intakes at a similar time as an intervention is begun, the subjects may show both some adaption to the change of calcium intake and a response to the intervention itself. The Institute of Medicine's Panel on Calcium and Related Nutrients recommended that rigorous methodology be followed in calcium balance studies20 to avoid confounding by changes in calcium absorption caused by changes in calcium intake.

Urinary calcium excretion is not a direct measure of osteoporosis or calcium balance, but rather a surrogate measure, because it is possible that there are differences in calcium absorption that offset any change in excretion.18, 21 Measures of calcium balance are superior measures of calcium status because they assess the effect of an intervention on the whole body retention of calcium and take alterations of absorption and/or endogenous secretion into account. The research question for this study was as follows: among adults, is there a dose‐response relationship between NAE and calcium balance? Specifically, the objective of this study was to use the techniques of meta‐analysis to assess the effect of changes in NAE on both urine calcium and calcium balance among studies with superior methodological quality for the study of calcium metabolism. As well, we examined the relationship between changes in NAE and the marker of bone metabolism, N‐terminal telopeptide of collagen from these studies.