Fenton · Nutrition journal 2011 · systematic review and meta-analysis · n=55 studies

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

Cited 114 times in the scientific literature.

Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of randomized intervention trials and prospective observational studies.

PubMed 21529374 · doi:10.1186/1475-2891-10-41 · record verified 2026-08-29

What was done

The authors conducted a systematic review and meta-analysis applying Bradford Hill's criteria for causality to evaluate the relationship between dietary acid load (the acid-ash hypothesis) and osteoporosis. They searched for randomized intervention trials, prospective cohort studies, meta-analyses, and cellular mechanism studies in healthy human adults. Interventions and exposures included modified dietary acid load, alkaline diets, or alkaline salts. Assessed bone-related outcomes included urinary calcium excretion, whole-body calcium balance or retention, changes in bone mineral density, and fractures. Fifty-five studies met inclusion criteria (22 randomized interventions, 2 meta-analyses, 11 prospective observational studies, and 19 in vitro cell studies).

What was found

The abstract reports no numerical effect sizes or confidence intervals. Urine calcium excretion increased with higher net acid excretion; however, calcium balance studies did not demonstrate loss of whole-body calcium. Randomized trials provided no direct evidence of osteoporosis progression (fragility fractures or bone strength by biopsy) and showed no adverse role for phosphate, milk, or grain foods. In vitro studies failed to demonstrate a biological mechanism functioning at physiological pH.

Why it matters

This review challenges the commercial and nutritional rationale for alkaline diets and supplements, showing that dietary acid load does not drive whole-body calcium depletion or osteoporotic bone disease.

Limits

The abstract provides no quantitative effect estimates. Intervention trials lacked direct clinical endpoints such as fractures or biopsy-measured bone strength. Furthermore, the included prospective cohort studies failed to control for critical osteoporosis risk factors, including baseline bone mineral density, estrogen status, family history, and weight loss during follow-up.

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