This systematic review, based on quality randomized trials and prospective observational studies, did not find support for the acid-ash hypothesis which states that "acid" from the modern diet causes osteoporosis or that an alkaline diet or "alkaline" supplements or salts prevent osteoporosis. Applying Hill's criteria to this body of evidence provides additional insight into the likelihood of causality based on established criteria. The criterion related to the strength of association partially was met because the quantity of urine calcium was related to the diet acid load, however, calcium balance which is the preferred measure of calcium metabolism, was not related to diet acid load. The criteria for the biological gradient, biologic plausibility, consistency and experimental evidence for a casual relationship for the acid ash hypothesis were lacking with regard to whole body calcium balance, bone resorption markers, and changes in BMD. Thus, claims that the modern "acid" producing diet causes osteoporosis were not substantiated by research evidence. These finding suggest there is not likely any bone health benefit from consumption of commercial products intended to counteract this dietary acid.
Hill's criterion requires consistent evidence from a variety of experimental designs and the studies of food estimates of acid load remain inconsistent and show only associations with urine calcium rather than a causal relationship for osteoporosis. Although there is general agreement in the commercial literature and advertising about which foods contribute acid and base, the foundation of these statements is weak and it is unclear whether the calculated amounts of acid or base have any association with health or disease.
In addressing these findings within the context of the existing acid-ash hypothesis, limitations to the evidence can be identified. Evidence or limitations to the evidence arise in the following areas: 1) lack of support for the hypothesis by well-designed calcium balance studies; 2) lack of well-designed studies with more direct measures of this disease (bone strength as measured by fragility fractures or biomechanical testing of bone biopsy material); 3) lack of control of important potential risk factors among the longitudinal cohort studies; and 4) lack of a defined mechanism that could occur at physiological pH. Small alterations in the surrogate measures of calcium in the urine and/or changes in BR markers are not evidence that alterations in the diet acid load cause bone demineralization. Additionally biological plausibility is questionable because of the conflicting roles of phosphate, sodium, potassium, protein and calcium interactions, and milk, since the roles put forth by the hypothesis differ from the actual roles of these molecules with respect to osteoporosis.
In the acid-ash model, sodium is one of the cations that has been assumed to represent base excretion, and cations theoretically protect against bone calcium losses [15
]. In the model of the acid-ash hypothesis, sodium is considered to have a similar bone protective effect to calcium, potassium, and magnesium. However, experts consider high sodium intakes to be a possible risk factor for bone mineral loss [48
]. It is possible that the acid-ash hypothesis is over simplistic in its categorization of sodium, potassium, calcium and magnesium as protective ions vis-à-vis
Early work to define food sources of acid and base began early in the previous century [110
]. Sherman published tables listing the acid and base contributions of 64 foods based on the ashed foods' mineral content in 1912 [110
]. Remer and Manz updated the original calculation in 1995 when they published newer tables of food acid loads with simple correction factors for each mineral designed to take imperfect absorption into account [152
]. The 1912 and 1995 food lists share a premise that urinary excretion of hydroxides of sodium, potassium, calcium and magnesium reflect "base" excretion while urinary protonated forms of phosphate, sulfate, and chloride reflect "acid" excretion [110
]. However, the assumption that food lists can reliably and exclusively classify foods as dietary sources of excreted acid or base is not supported by this review. The food lists categorize dietary phosphate and protein containing foods as acid sources anticipated to enhance bone loss, while evidence suggests that dietary phosphate does not increase calcium excretion (Figure ) or decrease calcium balance (Figure ), and dietary protein may enhance or protect BMD [263
]. Although Remer and Manz estimated that milk has a slight acidic load [152
], other investigators estimated that milk would supply an alkaline load [110
], and a recent study revealed that milk actually contributes an alkaline load [207
]. Grains were included in the food lists as acid generating, and have been considered "acid-yielding" [17
], but have not been evaluated for their hypothesized acidogenic and calciuric responses or effect on bone health, although two attempts have been made [133
The measurement of the diet acid load based on urine titratable acidity, ammonia and bicarbonate [14
] is not a precise estimate due to problems with each constituent [24
]. Ammonium (as ammonia) and bicarbonate (as CO2
) may be lost due to volatility [266
] prior to their measurement. Additionally, the measurement of titratable acidity is influenced by poor solubility of calcium, phosphorus, and uric acid, which can cause an over or underestimation of titratable acidity [24
]. Therefore the measurement of urinary acid excretion is error prone and may not accurately reflect the exposure to dietary acidity.
The majority of experimental evidence supporting the acid-ash hypothesis is derived from studies that have used urine calcium and/or BR markers as the outcome measure. Urine calcium changes are confounded by changes in calcium absorption. The estimated change in BR markers (Figures &) is less than the "least significant change" needed to consider that a true biological effect has occurred as opposed to a change due to measurement error [46
] and the results are inconsistent. The better-designed RCT which used changes of BMD as the outcome did not support the hypothesis [68
]. The lack of consistent information regarding the effects of protein, milk and grain foods on bone undermines support for the acid-ash hypothesis, and the unreliable measurement of acid excretion in urine further undermines the hypothesis (Table ). Therefore, the experimental evidence does not support the acid-ash hypothesis (Table ).
The acid-ash hypothesis recommends that to maintain bone health people consume generous quantities of fruit and vegetables (8 to 10 servings per day [145
]) along with modest amounts of grain and protein foods [21
]. Generous quantities of fruit and vegetables are not likely to be harmful and may have other health benefits [269
]. It is possible that fruit and vegetables are beneficial to bone health through mechanisms other than via the acid-ash hypothesis since there is some preliminary human and animal evidence that some fruits and some vegetables have supportive effects on bone [270
In contrast to the acid-ash hypothesis, recent research suggests that sufficient protein intake is needed for the maintenance of bone integrity [27
]. Changes in urine calcium and BR markers should not be considered proof of the acid-ash hypothesis.
Strengths and Limitations
The primary strengths of this study are that we conducted a broad search of the literature, only included studies with randomized or prospective cohort study designs, and focused on the higher quality randomized studies, evaluated these studies for risk of bias, as recommended for systematic reviews [36
]. We recognize the limitation of a systematic review is that the conclusions are based on the available studies. To formally reject the acid-ash hypothesis, well-designed unbiased studies with adequate rigor [34
] are needed, using direct measures for osteoporosis bone fragility: biomechanical testing of bone or the incidence of fragility fractures [259