Untangling the complex relationship between dietary acid load and glucocorticoid metabolism

Background: Evidence is growing that a high-acid diet might accelerate the rate of bone loss, and gene polymorphisms such as Interleukin 6 (IL6) -174G/C and -572G/C are related to bone deterioration. However, no study of the interaction between diet and IL6 polymorphisms has been conducted among Asians. Thus, the objective of this study was to determine whether IL6 gene polymorphisms modified the association between dietary acidity and the rate of bone resorption. Methods: This cross-sectional study recruited 203 postmenopausal women (age ranged from 51 to 85 years old) in community settings. The dietary intakes of the participants were assessed using a validated interviewer-administered semi-quantitative food frequency questionnaire (FFQ), while dietary acid load (DAL) was estimated using net endogenous acid production (NEAP). Agena® MassARRAY genotyping analysis and serum collagen type 1 cross-linked C-telopeptide (CTX1) were used to identify the IL6 genotype and as a bone resorption marker, respectively. The interactions between diet and single-nucleotide polymorphisms (SNPs) were assessed using linear regressions. Results: A total of 203 healthy postmenopausal women aged between 51 and 85 years participated in this study. The mean BMI of the participants was 24.3 kg/m2. In IL6 -174 G/C, all the participants carried the GG genotype, while the C allele was absent. Approximately 40% of the participants had a high dietary acid load. Dietary acid load (B = 0.15, p = 0.031) and the IL6 -572 CC genotype group (B = 0.14, p = 0.044) were positively associated with a higher bone resorption. However, there was no moderating effect of the IL6 genetic polymorphism on the relationship between and acid ash diet and bone resorption markers among the postmenopausal women (p = 0.79). Conclusion: High consumption of an acid ash diet and the IL6 -572 C allele seem to attribute to high bone resorption among postmenopausal women. However, our finding does not support the interaction effect of dietary acidity and IL6 (-174G/C and -572G/C) polymorphisms on the rate of bone resorption. Taken together, these results have given scientific research other candidate genes to focus on which may interact with DAL on bone resorption, to enhance planning for preventing or delaying the onset of osteoporosis among postmenopausal women.

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Net Endogenous Acid Excretion and Kidney Allograft Outcomes

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.00780121 ◽

2021 ◽

pp. CJN.00780121

Author(s):

Stanley Yeung ◽

Antonio Gomes-Neto ◽

Maryse Osté ◽

Else van den Berg ◽

Jenny Kootstra-Ros ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Failure ◽

Plasma Creatinine ◽

Transplant Recipients ◽

Acid Excretion ◽

Kidney Transplant Recipients ◽

Dietary Acid Load ◽

Dietary Acid ◽

Acid Load ◽

Net Acid Excretion

Background and objectives: High dietary acid load may accelerate kidney function decline. We prospectively investigated whether dietary acid load is associated with graft outcomes in kidney transplant recipients and whether venous bicarbonate (HCO3−) mediates this association. Design, setting, participants and measurements: We used data from 642 kidney transplant recipients with a functioning graft ≥1 year after transplantation. Net endogenous acid production (NEAP) was estimated using food frequency questionnaires (FFQ) and, alternatively, 24-hour urinary urea and potassium excretion to estimate NEAPUrine. We defined composite kidney endpoint as doubling of plasma creatinine or graft failure. Multivariable Cox regression analyses, adjusted for potential confounders, were used to study the associations of dietary acid load with kidney endpoint. We evaluated potential mediation effects of venous HCO3− , urinary HCO3− excretion, urinary ammonium (NH4+) excretion, titratable acid excretion, and net acid excretion on the association between NEAP and kidney endpoint. Results: Median NEAPFFQ and NEAPUrine were 40 (Interquartile range [IQR] 35-45) and 54 (IQR 44-66) mEq/day, respectively. During a median follow-up time of 5.3 (IQR 4.1-6.0) years, 121 (19%) participants reached kidney endpoint. After multivariable adjustment, NEAPFFQ and NEAPUrine (per SD higher) were independently associated with higher risk for kidney endpoint (hazard ratio [HR] 1.33; 95% confidence interval [CI] 1.12-1.57, P=0.001 and HR 95%CI, 1.44 [1.24-1.69], P<0.001 resp.). Baseline venous HCO3− mediated 20% of the association between NEAPFFQ and kidney endpoint. Baseline venous HCO3−, urinary NH4+ excretion and net acid excretion mediated 25%, -14% and -18% resp. of the association between NEAPUrine and kidney endpoint. Conclusion: Higher dietary acid load was associated with a higher risk of doubling of plasma creatinine or graft failure, and this association was partly mediated by venous HCO3−, urinary NH4+ and net acid excretion.

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Dietary Acid Load, IGF-1 Single Nucleotide Polymorphism and Bone Resorption among Postmenopausal Chinese Women

Nutrients ◽

10.3390/nu10070915 ◽

2018 ◽

Vol 10 (7) ◽

pp. 915 ◽

Cited By ~ 1

Author(s):

Sook Lim ◽

Mohd Zalilah ◽

Yit Chin ◽

Vasudevan Ramachandran ◽

Yoke Chan

Keyword(s):

Physical Activity ◽

Single Nucleotide Polymorphism ◽

Bone Resorption ◽

Chinese Women ◽

National Council ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Dietary Acid Load ◽

Dietary Acid ◽

Acid Load

The interaction of dietary and genetic factors may affect the development of bone deterioration. This study investigated whether the effects of dietary acid load (DAL) on bone loss in postmenopausal Chinese women were moderated by the insulin-like growth factor-1 (IGF-1) single nucleotide polymorphism, a known gene that plays a role in the regulation of bone formation and bone remodeling. A total of 217 healthy participants were recruited from the National Council of Senior Citizens Organizations Malaysia. Serum collagen type 1 cross-linked C-telopeptide was used as a surrogate bone marker to assess bone resorption and Agena® MassARRAY genotyping analysis was used to identify the signaling of IGF-1 rs35767. The dietary acid load was measured by potential renal acid load score while physical activity was ascertained using the Global Physical Activity Questionnaire. Hierarchical regression was applied to test the main and interaction effects of DAL and IGF-1 genotypes in bone resorption. The result supported the diet-dependent acid-base balance theory that higher DAL was positively associated with bone resorption (β = 0.152, p = 0.031, F(6,207) = 2.11, sig-F = 0.036, R2 = 0.079). However, the results indicated that there was no significant correlation between IGF-1 and bone resorption, or any significant interaction between DAL and IGF-1. In conclusion, there was no moderating effect of IGF-1 on the relationship between DAL and bone resorption.

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Dietary Acid Load and Blood Pressure in Healthy Adults

The FASEB Journal ◽

10.1096/fasebj.2021.35.s1.04279 ◽

2021 ◽

Vol 35 (S1) ◽

Author(s):

Michael Axler ◽

Andrea Lobene ◽

Katarina Smiljanec ◽

Macarena Ramos Gonzalez ◽

Alexis Mbakwe ◽

...

Keyword(s):

Blood Pressure ◽

Healthy Adults ◽

Dietary Acid Load ◽

Dietary Acid ◽

Acid Load

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Low Estimates of Dietary Acid Load Are Positively Associated with Bone Ultrasound in Women Older Than 75 Years of Age with a Lifetime Fracture

Journal of Nutrition ◽

10.1093/jn/138.7.1349 ◽

2008 ◽

Vol 138 (7) ◽

pp. 1349-1354 ◽

Cited By ~ 27

Author(s):

Emma Wynn ◽

Susan A. Lanham-New ◽

Marc-Antoine Krieg ◽

David R. Whittamore ◽

Peter Burckhardt

Keyword(s):

Bone Ultrasound ◽

Dietary Acid Load ◽

Dietary Acid ◽

Acid Load

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Race/Ethnicity, Dietary Acid Load, and Risk of End-Stage Renal Disease among US Adults with Chronic Kidney Disease

American Journal of Nephrology ◽

10.1159/000487715 ◽

2018 ◽

Vol 47 (3) ◽

pp. 174-181 ◽

Cited By ~ 10

Author(s):

Deidra C. Crews ◽

Tanushree Banerjee ◽

Donald E. Wesson ◽

Hal Morgenstern ◽

Rajiv Saran ◽

...

Keyword(s):

Renal Disease ◽

End Stage Renal Disease ◽

Risk Model ◽

Caloric Intake ◽

Dietary Acid Load ◽

Dietary Acid ◽

Acid Load ◽

Race Ethnicity ◽

Stage Renal Disease ◽

End Stage

Background: Dietary acid load (DAL) contributes to the risk of CKD and CKD progression. We sought to determine the relation of DAL to racial/ethnic differences in the risk of end-stage renal disease (ESRD) among persons with CKD. Methods: Among 1,123 non-Hispanic black (NHB) and non-Hispanic white (NHW) National Health and Nutrition Examination Survey III participants with estimated glomerular filtration rate 15–59 mL/min/1.73 m2, DAL was estimated using the Remer and Manz net acid excretion (NAEes) formula and 24-h dietary recall. ESRD events were ascertained via linkage with Medicare. A competing risk model (accounting for death) was used to estimate the hazard ratio (HR) for treated ESRD, comparing NHBs with NHWs, adjusting for demographic, clinical and nutritional factors (body surface area, total caloric intake, serum bicarbonate, protein intake), and NAEes. Additionally, whether the relation of NAEes with ESRD risk varied by race/ethnicity was tested. Results: At baseline, NHBs had greater NAEes (50.9 vs. 44.2 mEq/day) than NHWs. It was found that 22% developed ESRD over a median of 7.5 years. The unadjusted HR comparing NHBs to NHWs was 3.35 (95% CI 2.51–4.48) and adjusted HR (for factors above) was 1.68 (95% CI 1.18–2.38). A stronger association of NAE with risk of ESRD was observed among NHBs (adjusted HR per mEq/day increase in NAE 1.21, 95% CI 1.12–1.31) than that among NHWs (HR 1.08, 95% CI 0.96–1.20), p interaction for race/ethnicity × NAEes = 0.004. Conclusions: Among US adults with CKD, the association of DAL with progression to ESRD is stronger among NHBs than NHWs. DAL is worthy of further investigation for its contribution to kidney outcomes across race/ethnic groups.

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The Serum Metabolome Identifies Biomarkers of Dietary Acid Load in 2 Studies of Adults with Chronic Kidney Disease

Journal of Nutrition ◽

10.1093/jn/nxy311 ◽

2019 ◽

Vol 149 (4) ◽

pp. 578-585 ◽

Cited By ~ 6

Author(s):

Casey M Rebholz ◽

Aditya Surapaneni ◽

Andrew S Levey ◽

Mark J Sarnak ◽

Lesley A Inker ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Fruits And Vegetables ◽

Smoking Status ◽

Cross Sectional ◽

Dietary Acid Load ◽

Nutrition Research ◽

Net Endogenous Acid Production ◽

Dietary Acid ◽

Acid Load

ABSTRACT Background Dietary acid load is a clinically important aspect of the diet that reflects the balance between acid-producing foods, for example, meat and cheese, and base-producing foods, for example, fruits and vegetables. Methods We used metabolomics to identify blood biomarkers of dietary acid load in 2 independent studies of chronic kidney disease patients: the African American Study of Kidney Disease and Hypertension (AASK, n = 689) and the Modification of Diet in Renal Disease (MDRD, n = 356) study. Multivariable linear regression was used to assess the cross-sectional association between serum metabolites whose identity was known (outcome) and dietary acid load (exposure), estimated with net endogenous acid production (NEAP) based on 24-h urine urea nitrogen and potassium, and adjusted for age, sex, race, randomization group, measured glomerular filtration rate, log-transformed urine protein-to-creatinine ratio, history of cardiovascular disease, BMI, and smoking status. Results Out of the 757 known, nondrug metabolites identified in AASK, 26 were significantly associated with NEAP at the Bonferroni threshold for significance (P < 6.6 × 10−5). Twenty-three of the 26 metabolites were also identified in the MDRD study, and 13 of the 23 (57%) were significantly associated with NEAP (P < 2.2 × 10−3), including 5 amino acids (S-methylmethionine, indolepropionylglycine, indolepropionate, N-methylproline, N-δ-acetylornithine), 2 cofactors and vitamins (threonate, oxalate), 1 lipid (chiro-inositol), and 5 xenobiotics (methyl glucopyranoside, stachydrine, catechol sulfate, hippurate, and tartronate). Higher levels of all 13 replicated metabolites were associated with lower NEAP in both AASK and the MDRD study. Conclusion Metabolomic profiling of serum specimens from kidney disease patients in 2 study populations identified 13 replicated metabolites associated with dietary acid load. Additional studies are needed to validate these compounds in healthy populations. These 13 compounds may potentially be used as objective markers of dietary acid load in future nutrition research studies.

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