Osteoporosis is a major health threat characterized by skeletal fragility and microarchitectural deterioration (1–3). Factors associated with bone health include sex, physical inactivity, alcohol consumption, smoking, loss of estrogen, and diet (4). Previous studies have documented that adequate calcium intake and appropriate nutrient status are essential for the prevention of osteoporosis and its devastating consequences. In addition to individual dietary components for improving musculoskeletal health, a balanced diet is also important (5). The high dietary acid load (DAL) represents a diet rich in nutrients that are metabolized to non-carbonic acids such as sulfuric acid in amounts greater than the alkaline bicarbonate produced by the combustion of organic salts like potassium chloride provided by fruit and vegetable consumption (6). Therefore, foods containing sulfate and phosphorus such as meat, fish, cheese, grain products, and rice are considered acidogenic (7, 8). While foods rich in bicarbonate, potassium, magnesium, and calcium, such as fruit, legumes, vegetables, red wine, and potatoes, are considered alkaline (9). Epidemiological and scientific researchers have indicated that following a Western dietary pattern, composed largely of acidogenic foods, might lead to excess endogenous acid production, and consequently, low-grade metabolic acidosis (6–9). Metabolic acidosis releases calcium from the bone matrix mediated for increasing osteoclastic resorption to maintain homeostasis, weakening the bone and making it susceptible to fracturing (9, 10). Such evidence raises the question of whether long-term adherence to diets with high acidity potential might contribute to the loss of bone mass and osteoporosis (11–13). Findings on the association between dietary acid load (DAL) and bone health are controversial. While some studies have documented that a high DAL was associated with a reduction in the density and structure of bone mass (14–18), others failed to find such evidence (19, 20). This inconsistency has also been documented for observational studies that investigated the association of DAL with fracture risk (14, 21). A recent meta-analysis did not provide evidence for a protective effect of alkaline diet on bone health (22). However, several studies have been published since the release of that meta-analysis. Moreover, that meta-analysis did not consider (NEAP) and potential renal acid load (PRAL) separately. Therefore, in the current study we aimed to summarize the available evidence on the association between DAL and risk of fractures and bone mineral density (BMD) in adults, by considering two major methods for estimating DAL including PRAL and NEAP.

This meta-analysis was conducted using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.

The present study is the first meta-analysis summarizing observational evidence on the association between indices of diet-dependent acid load and risk of fractures and BMD. Our results showed no significant association between DAL, represented by PRAL and NEAP, and risk of fractures. In addition, we found that high NEAP scores were significantly associated with a slightly lower femoral and spinal BMD. However, there was no significant association between dietary PRAL score and BMD.

The social and economic burden of osteoporotic fractures is increasing worldwide as the population ages. Fracture prevention has therefore become a major public health priority. Dietary variables have an important role in these conditions. Some diet components might have potential effects on the acid-base balance of the body due to the PH-altering features (38). Animal foods such as meat, fish, chicken, cheese, egg, and cereals are good sources of sulfur amino acids, phosphate, and chloride and are considered acid-forming foods. However, foods providing base precursors such as fruits and vegetables are rich in glutamate, citrate, and malate. Therefore, dietary patterns rich in animal foods and low in plant foods like Western-style dietary patterns might alter the body's acid-base balance (38). According to the regulation of acid-base balance in a narrow range, any imbalances in blood pH or bicarbonate buffer can affect overall health.

The current study provides reliable evidence on the association between DAL and bone health. We failed to find a clear association between DAL (based on PRAL and NEAP) and risk of fractures. A meta-analysis of cohort studies that examined the association of protein intake and bone health throughout the life course reported that total, animal, and plant protein intake was not associated with risk of osteoporotic fractures in healthy adults (39). A prospective cross-sectional analysis showed that urinary citrate, a biomarker for diet- and metabolism-dependent acid-base status, was inversely associated with fracture risk in adult females but not in males (40). In another meta-analysis, adopting “Healthy” dietary patterns reduced the risk of fractures, while the risk of fracture could be increased with the “Meat/Western” dietary pattern (41). Moreover, long-term observational studies documented that a high intake of some alkaline foods such as fruits and vegetables was associated with a lower risk of fracture (42). In the interpretation of these discrepancies, it must be considered that other dietary components and biologically active factors in the acid/base-forming foods and dietary patterns could also affect bone fracture. Further investigations are needed to find the exact relationship between DAL and risk of fractures.

The present review found that NEAP was inversely associated with a slightly lower BMD. However, there was no significant relationship between PRAL and spinal and femoral BMD. It appears that the different nutrients used in the calculation of NEAP and PRAL could be a contributing factor to the observed variations (43). Compared to NEAP, PRAL measures absorption rates of contributing nutrients from the gut (43). Moreover, the study by Remer et al. indicated that PRAL values were significantly correlated with net acid excretion in 24-h urine samples compared with NEAP (8). A systematic review and meta-analysis did not support the acid-ash hypothesis and concluded there is no evidence that an alkaline diet is a protective determinant of bone health (22). This hypothesis states that acid-forming foods like those found in the modern diet cause osteoporosis and alkaline-forming foods or supplements prevent osteoporosis. However, that study did not conduct any further statistical analysis but only applied the Hill standard review to retrospectively describe the relationship between acid load and bone metabolism. In an additional meta-analysis of 13 randomized clinical trials, alkaline supplementation had beneficial effects on bone metabolism and acidic diets were not harmful for bone health (44). Several randomized controlled trials have reported that high-protein diets which are considered acid-producing diets, have no significant effect on bone turnover markers and BMD (45, 46). Finding from an umbrella review indicated that an appropriate intake of dairy products, vegetables, fruits, and micronutrients and a lower intake of alcohol and coffee could reduce the risk of osteoporosis (47). It is possible that fruit and vegetables may be beneficial for bone health through mechanisms other than via the acid-base balance. Further studies should examine whether fruit and vegetables protect from the bone.

Several mechanisms have been proposed to explain how DAL might affect bone health (13, 48, 49). It is well known that bone acts as the primary buffering system for alkali components such as calcium and potassium in case of systemic acidosis (50). On the other hand, metabolic acidosis releases calcium from the bone matrix, weakening the bone and making it more prone to fracture by increasing osteoclastic resorption to maintain homeostasis (9, 10). Metabolic acidosis can also affect bone health by reducing insulin sensitivity and impairing glucose homeostasis, leading to inflammation and oxidative stress (51, 52). Thus, insulin resistance and inflammation are considered potential risk factors to explain the association between acidity and bone health.

In the current meta-analysis, adherence to diets with high acidity potential was not associated with risk of fractures. Furthermore, we found a significant weak association between NEAP and BMD. However, DAL based on PRAL was not associated with BMD. These findings thus have important public health implications. The current study provides further evidence that higher DAL is not associated with fracture risk and is weakly associated with BMD. However, these findings should be interpreted with caution and further large intervention trials are required.

The original contributions presented in the study are included in the article/Supplementary Materials, further inquiries can be directed to the corresponding author.

FG conceived and designed the study, conducted systematic search, screened and selected eligible articles, data interpretation, and manuscript drafting. SN performed analyses and interpreted results, data interpretation, and manuscript drafting. MS and NR screened and selected eligible articles and extracted information. KM is the guarantor. All authors contributed to writing, reviewing or revising the paper and have approved it for publication.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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