U-Shaped Association between Dietary Acid Load and Risk of Osteoporotic Fractures in 2 Populations at High Cardiovascular Risk

Abstract

Background Bone contributes to maintaining the acid-base balance as a buffering system for blood pH. Diet composition also affects acid-base balance. Several studies have linked an imbalance in the acid-base system to changes in the density and structure of bone mass, although some prospective studies and meta-analyses suggest that acid load has no deleterious effect on bone. Objective The aim of this study was to examine the associations between potential renal acid load (PRAL) and net endogenous acid production (NEAP) and the risk of osteoporotic fractures and bone mineral density (BMD) in 2 middle-aged and elderly Mediterranean populations. Methods We conducted a longitudinal analysis including 870 participants from the PREvención con DIeta MEDiterranea (PREDIMED) Study and a cross-sectional analysis including 1134 participants from the PREDIMED-Plus study. Participants were adults, aged 55–80 y, either at high cardiovascular risk (PREDIMED) or overweight/obese with metabolic syndrome (PREDIMED-Plus), as defined by the International Diabetes Federation, the American Heart Association, and the National Heart Association. PRAL and NEAP were calculated from validated food-frequency questionnaires. BMD was measured using DXA scans. Fracture information was obtained from medical records. The association between mean PRAL and NEAP and fracture risk was assessed using multivariable-adjusted Cox models. BMD differences between tertiles of baseline PRAL and NEAP were evaluated by means of ANCOVA. Results A total 114 new fracture events were documented in the PREDIMED study after a mean of 5.2 y of intervention and 8.9 y of total follow-up. Participants in the first and third PRAL and NEAP tertiles had a higher risk of osteoporotic fracture compared with the second tertile, showing a characteristically U-shaped association [HR (95% CI): 1.73 (1.03, 2.91) in tertile 1 and 1.91 (1.14, 3.19) in tertile 3 for PRAL, and 1.83 (1.08, 3.09) in tertile 1 and 1.87 (1.10, 3.17) in tertile 3 for NEAP]. Compared with the participants in tertile 1, the participants in the top PRAL and NEAP tertiles had lower BMD [PRAL: mean total femur BMD: 1.029 ± 0.007 and 1.007 ± 0.007 g/cm2; P = 0.006 (tertiles 1 and 3); NEAP: mean total femur BMD: 1.032 ± 0.007 and 1.009 ± 0.007 g/cm2; P = 0.017 (tertiles 1 and 3)]. Conclusions The results of our study suggest that both high and low dietary acid are associated with a higher risk of osteoporotic fractures, although only high dietary acid was found to have a negative relation to BMD in senior adults with existing chronic health conditions. This trial was registered at http://www.isrctn.com/ as ISRCTN3573963 (PREDIMED) and ISRCTN89898870 (PREDIMED-Plus).

Dietary acid load is associated with primary osteoporosis in postmenopausal women aged 50–65 years: A cross‐sectional study

“…The difference in the intake of protein and phosphorus was not statistically significant between groups in the present study. In the study of García‐Gavilán et al ( 2021 ), calcium, protein, magnesium, and phosphorus intake was higher in the osteoporosis group, but potassium intake was significantly lower ( p < .05). The reason for the possible difference in the inclusion criteria could be that the participants in the study were adults 55–80 years old at high risk of cardiovascular disease or overweight or obese people with metabolic syndrome.…”

“…The authors reported that the risk of fracture is inversely related to women's urinary citrate but positively correlated with PRAL in women (Esche et al, 2016 ). According to this hypothesis, a high‐acidity diet can increase the risk of osteoporosis and fractures related to decreased bone density, while consumption of alkaline‐producing foods can prevent acid‐dependent bone loss (García‐Gavilán et al, 2021 ). Some observational studies and meta‐analyses dispute the claim that acid loads generally have a detrimental effect on bone (De Jonge et al, 2017 ; Fenton et al, 2011 ; McLean et al, 2011 ).…”

Osteoporosis epidemiology using international cohorts

“…Most notably, a study in more than 25 000 British adults followed for a mean of almost 18 years [1 ▪▪ ] found a significantly higher fracture risk in persons with the highest quintile of dietary acid load compared with the lowest quintile. A secondary analysis of a Mediterranean diet trial in subjects at increased risk of ischemic heart disease (IHD) also confirmed a relationship between dietary acid load and the risk of fractures but in this patient group the relationship was more compatible with a U-shaped relationship with the mid tertile being at lowest risk [2]. Further, an Australian cohort study found lower annual loss rates for hip BMD in people with high Western or Animal Protein diet scores [3].…”

Dietary Acid Load and Bone Health: A Systematic Review and Meta-Analysis of Observational Studies

“…Among these, three publications were excluded due to same exposure and outcome variables (14), irrelevant outcomes (27), and being a conference paper (28). Finally, 14 publications were included in the systematic review (15,17,(19)(20)(21)(29)(30)(31)(32)(33)(34)(35)(36)(37) and ten publications were included in the meta-analysis (17,19,21,(29)(30)(31)(33)(34)(35)(36).…”

“…While some studies have documented that a high DAL was associated with a reduction in the density and structure of bone mass (14)(15)(16)(17)(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 metaanalysis did not provide evidence for a protective effect of alkaline diet on bone health (22).…”