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Table 5 Summary Table of the Evaluation of the Acid-ash Hypothesis using Hill's Criteria

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

Hill's criterion Is criterion met? Reason
Temporality Yes, by inclusion criteria Papers were included only if this Temporality criterion was met, that is the exposure preceded the outcome.
Strength Yes Estimates of calcium loss in the urine are of sufficient magnitude to explain the progression of osteoporosis, while calcium balance studies do not show support of the acid ash hypothesis.
Biological Gradient or Dose-response No While urine calcium changes in response to changes in net acid excretion, calcium balance does not. Calcium balance is a better measure of whole body calcium metabolism than urine calcium.
Biologically Plausible No No defined mechanism that could take place at physiological pH.
  No Problems with the hypothesis due to the incongruent roles of phosphate, sodium, and protein with bone, and lack of support for the role of potassium.
Consistency No The prospective observational cohort studies have not consistently controlled for the key osteoporosis risk factors, putting their findings into question.
  No The estimated effects of protein, milk and grain foods are not supported by evidence.
  No The measurement of urinary acid excretion is not a precise science and measurements may be inaccurate.
Experiments No The outcome measures used to date in experimental studies are only surrogate measures or correlates of bone strength. The majority of experimental evidence supporting the acid-ash hypothesis is from studies that used urine calcium and/or bone resorption markers as the outcomes, which are surrogate measures of bone strength.
  No The RCT that assessed changes of BMD with the lower risk of bias did not support the hypothesis. Therefore, the experimental evidence does not support the hypothesis
  No Meta-analyses of bone resorption markers in response to changes in acid and alkali loads did not support the hypothesis whether all of the study results were combined or only studies that followed recommendations for bone markers were assessed.