Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality

Abstract

Background: Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria.

Methods: Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined.

Results: Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies did not provide evidence for an adverse role of phosphate, milk, and grain foods in osteoporosis.

Conclusions: A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health.

Figure 1

Flow diagram of studies identified, excluded and included in the systematic review.

Figure 2

The relationship between change in NAE and change in urinary calcium, limited to randomized studies that followed the Institute of Medicines' guidelines for calcium metabolism studies (R2 = 0.406; p < 0.0001). This material is reproduced with permission of John Wiley & Sons, Inc. from Fenton et al. J Bone Miner Res 2009;24:1835-1840.

Figure 3

No relationship between change in NAE and change in calcium balance, analysis limited to randomized studies that followed the Institute of Medicines' guidelines for calcium metabolism studies (R2 = 0.003; p = 0.38). This material is reproduced with permission of John Wiley & Sons, Inc. from Fenton et al. J Bone Miner Res 2009;24:1835-1840.

Figure 4

The relationship between phosphate supplementation and change urine calcium, limited to randomized studies that followed the Institute of Medicines' guidelines for calcium metabolism studies (R² = 0.185 p < 0.001).

Figure 5

The relationship between phosphate supplementation and change calcium balance, limited to randomized studies that followed the Institute of Medicines' guidelines for calcium metabolism studies (R² = 0.704, p < 0.001).

Figure 6

Changes of bone resorption markers in response to a more alkaline diet. The results were heterogeneous (p = 0.02), therefore it was not considered valid to combine them and examine the test for overall effect.

Figure 7

Changes of bone resorption markers in response to a more alkaline diet, measured while subjects were fasting. The relationship between interventions to alter the diet acid load on bone resorption markers was not significant effect (p-value = 0.91).