Net Endogenous Acid Production Research Articles

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

BackgroundBone 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. ObjectiveThe 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. MethodsWe 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. ResultsA 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)]. ConclusionsThe 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).

No Interaction Effect between Interleukin-6 Polymorphisms and Acid Ash Diet with Bone Resorption Marker in Postmenopausal Women

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.

Dietary acid load and lung cancer risk: A case-control study in men

Dysregulation of the endogenous acid-base balance can contribute to inflammation and cancer development if metabolic acidosis is sustained. The epidemiologic evidence on the association between diet-dependent acid load and cancer risk is scarce and inconsistent. We aim to explore the possible role of dietary acid load in lung cancer (LC) risk. A case-control study was performed on 843 LC cases and 1466 controls by using a multi-topic questionnaire, including a food frequency questionnaire. Controls were matched to cases by age-frequency, urban/rural residence, and region. Food-derived nutrients were calculated from available databases. The dietary acid load was calculated using validated measures as potential renal acid load (PRAL) score and net endogenous acid production (NEAP) score. Odds ratios (ORs) were estimated by logistic regression. We found direct associations between dietary acid load and LC risk. The highest quartile of the NEAP score was significantly associated (OR=2.22, ptrend<0.001). The PRAL score displayed similar associations in simpler regression models, but there was no association when a more complex one was used (OR=0.99, ptrend =0.94). The NEAP score was associated with a significant risk increase in all cell types, except for small cell cancers, but the PRAL score did not show any association. The NEAP scores, directly associated with meat intake and inversely associated with plant-based foods intake, suggest that a high acid load dietary style may increase LC risk. Studies focused on food groups, and nutritional patterns are in line with our findings. Although the data shown here represent the first one to be published on this issue, further studies are needed to confirm these findings.

Dietary Acid Load, Past Smoking Intensity and Mortality Among Breast Cancer Survivors

Cancer survivors are at accelerated risk of aging and more susceptible to unhealthy diets and lifestyles than people without cancers. However, current dietary guidelines for cancer survivors not quite different from that for general healthy population. Further, these guidelines are not specific for cancer survivors who are past smokers. Acid-producing diet can accelerate aging and stimulate cancer development if acid-base balance is not regulated properly. Cancer survivors and past smokers have reduced capacities to adjust acid-base balance. Thus, we conducted prospective cohort analyses among 2950 early-stage breast cancer survivors who enrolled in the Women’s Healthy Eating and Living study and provided dietary information through 24-hour recalls at baseline and during follow-up. We assessed dietary acid load using two common dietary acid load scores, potential renal acid load (PRAL) score, and net endogenous acid production (NEAP) score. We assessed past smoking intensity by pack-years of smoking. After an average of 7.3 years of follow-up, there were 295 total death, and 249 breast cancer-specific death. Increased PRAL and NEAP scores were positively associated with total mortality and breast cancer-specific mortality (p for trend <0.1 for PRAL and <0.01 for NEAP). Further, dietary acid load and pack-years of smoking had joint positive associations with mortalities (Comparing the highest to the lowest categories, risk increased by 2.5-3 times; P for trend <0.01 for both PRAL and NEAP). Our study provides valuable evidence for adding dietary acid load to dietary guidelines for breast cancer survivors and developing specific guidelines for past smokers.

Positive association between dietary acid load and future insulin resistance risk: findings from the Korean Genome and Epidemiology Study

BackgroundAcid-base homeostasis is increasingly being recognized to play an important role in normal metabolic function. However, prospective studies on the relationship between diet-induced acid-base imbalance and insulin resistance among Asian populations have been limited. Thus, we investigated whether diet-induced metabolic acidosis was prospectively associated with insulin resistance risk in middle-aged and older Korean adults.MethodsIn total, 5406 participants from the Korean Genome and Epidemiology Study without type 2 diabetes, insulin resistance, cancer, or renal diseases at baseline examination were included in this study. To estimate diet-induced metabolic acidosis, we used potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores calculated from the usual dietary intake assessed by a validated 103-item food frequency questionnaire at baseline. Multivariable Cox proportional hazard models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of insulin resistance incidence.ResultsDuring a mean follow-up period of 7.4 years, we documented 3449 insulin resistance cases. In the fully adjusted model, the future insulin resistance risk was significantly higher among participants in the highest quartiles of PRAL (HR: 1.30, 95% CI: 1.13–1.48, Ptrend = 0.0002) and NEAP (HR: 1.30, 95% CI: 1.14–1.49, Ptrend = 0.0008) than among those in the lowest quartiles. Associations were slightly strengthened among men, adults < 50 years old, obese participants, or those with low physical activity levels.ConclusionsOur findings suggested that diet-dependent acid load was positively associated with the future development of insulin resistance, suggesting effect modification by sex, age, the presence of obesity, and physical activity levels.

Acid-Producing Diet and Depressive Symptoms among Breast Cancer Survivors: A Longitudinal Study

Simple SummaryDepressive symptoms, which are highly prevalent among breast cancer survivors, can significantly influence quality of life and increase total mortality. The aim of our prospective study was to determine whether acid-producing diets have an adverse impact on depression. Our study demonstrated that a higher consumption of acid-producing diets was significantly associated with depressive symptoms among breast cancer survivors, especially among those who were younger than 55 and had a sedentary lifestyle.The incidence of depression is two-to-three times higher in cancer survivors than the general population. Acid-producing diets may play important roles in the development of depression. Cancer survivors are more susceptible to acid-producing diets, yet few prospective studies have investigated the association of acid-producing diets with depression among breast cancer survivors. We leveraged a large cohort of 2975 early stage breast cancer survivors, which collected detailed dietary data via 24-h recalls. Potential renal acid load (PRAL) and net endogenous acid production (NEAP), two commonly used dietary acid load scores, were used to estimate acid-producing diets. Intakes of PRAL and NEAP were assessed at baseline and years one and four. Increased PRAL and NEAP were each independently associated with increased depression in the longitudinal analyses, after adjusting for covariates. The magnitude of the associations was stronger for PRAL than NEAP. Women with the highest quartile intakes of PRAL had 1.34 (95% CI 1.11–1.62) times the risk of depression compared to women with the lowest quartile. Furthermore, we also observed a joint impact of PRAL and younger age on depression, as well as a joint impact of PRAL and physical activity on depression. Decreasing the consumption of acid-producing diets may be a novel and practical strategy for reducing depressive symptoms among breast cancer survivors, especially those who are younger and have a sedentary lifestyle.

Higher Dietary Acid Load Is Associated With an Increased Risk of Calcium Oxalate Kidney Stones

Diet-dependent net acid load may influence the risk of kidney stone formation by affecting calcium and citrate excretion. However, to date, little research has investigated the relationship between dietary acid load and kidney stones. Therefore, this study sought to assess whether a diet high in potential acid load was related to the risk of calcium oxalate stone formation. This case-control study was conducted on 430 participants (including 215 newly diagnosed patients with calcium oxalate stones and 215 controls matched for sex and age). Dietary intake was assessed using a validated food frequency questionnaire over the preceding year. Dietary acid load was estimated based on the potential renal acid load (PRAL) and net endogenous acid production (NEAP). The association between dietary acid load indices and kidney stone was examined using multivariable logistic regression. Mean PRAL (standard error) was significantly lower in cases versus controls (-5.3±1.3 vs. -1.7±1.3, P=.048). Corresponding values for NEAP were 39.4±0.8 and 41.8±0.8, respectively (P=.032). After adjustment for potential confounders, the odds ratios (95% confidence intervals) of calcium oxalate stones in the top tertile of PRAL and NEAP were 1.45 (0.89-2.38, P=.136) and 1.88 (1.14-3.09, P=.013), respectively. Adjustment for potassium and protein in 2 separate models did not substantially change the results. A diet high in potential acid load, measured by NEAP, was associated with higher risk of calcium oxalate stone formation, independent of potassium and protein intake. Prospective longitudinal studies are warranted to confirm the veracity of our results.

Associations between plant-based dietary indices and dietary acid load with cardiovascular risk factors among diabetic patients

To study how a plant-based diet and dietary acid load (DAL) are related to cardiovascular disease (CVD) risk factors among type 2 diabetic women. In this cross-sectional study, a validated food frequency questionnaire was used to assess the dietary intake of 230 diabetic women. We created a plant-based dietary index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI). DAL was calculated based on potential renal acid load (PRAL) and net endogenous acid production (NEAP). Patients in the highest tertile of PDI had lower fasting blood sugar (146.74 ± 6.16 vs. 152.87 ± 6.09, p = 0.009) and lower 2-h postprandial glucose (181.76 ± 7.03 vs. 203.01 ± 6.94, p = 0.002). Patients in the highest tertile of PDI were at lower risk of high waist circumference in a crude model (odd ratios: 0.43; 95% CI: 0.19; 0.96, p = 0.039); however, this association did not reach statistical significant after adjustment for confounders. Our study suggests that plant-based dietary indices and DAL are not associated with CVD risk factors among diabetic patients.

Performance of Predictive Equations and Biochemical Measures Quantifying Net Endogenous Acid Production and the Potential Renal Acid Load

IntroductionA limited number of studies have assessed the accuracy and precision of methods for determining the net endogenous acid production (NEAP) and its components. We aimed to investigate the performance of methods quantifying the diet dependent acid–base load.MethodsData from metabolic balance studies enabled calculations of NEAP according to the biochemical measures (of net acid excretion [NAE], urinary net endogenous acid production [UNEAP], and urinary potential renal acid load [UPRAL]) as well as estimative diet equations (by Frassetto et al., Remer and Manz, Sebastian et al., and Lemann) that were compared among themselves in healthy participants fed both acid and base forming diets for 6 days each.ResultsSeventeen participants (mean ± SD age, 60 ± 8 years; body mass index, 23 ± 2 kg/m2) provided 102 twenty-four-hour urine samples for analysis (NAE, 39 ± 38 mEq/d [range, −9 to 95 mEq/d]). Bland-Altman analysis comparing UNEAP to NAE showed good accuracy (bias, −2 mEq/d [95% confidence interval {CI}, −8 to 3]) and modest precision (limits of agreement, −32 to 28 mEq/d). Accurate diet equations included potential renal acid load (PRAL) by Sebastian et al. (bias, −4 mEq/d [95% CI, −8 to 0]) as well as NEAP by Lemann et al. (bias, 4 mEq/d [95% CI, −1 to 9]) and Remer and Manz (bias, −1 mEq/d [95% CI, −6 to 3]).ConclusionsResearchers are encouraged to collect measures of UPRAL and UNEAP; however, investigators drawing conclusions between the diet-dependent acid–base load and human health should consider the limitations within all methods.

Dietary Acid-Base Balance in High-Performance Athletes.

Physical exercise leads to metabolic changes that affect the acid-base balance in skeletal muscles and other tissues. Nutrition is one of the factors that may influence the acid-base balance in the body. Keeping alkaline circumstances in the body is important not only for health and athletic performance in training but also during competition in many sport events. This is especially significant for athletes who practice in sport at the highest level of competition. The aim of the study was to determine the dietary acid-base balance in competitive Lithuanian high-performance athletes, and to evaluate the effect of actual diets of athletes on NEAP (net endogenous acid production), muscle mass and body mineral content during a four-year Olympic cycle. The research participants were 18.1 ± 3.3-year-old Lithuanian high performance athletes (n = 323). The actual diet was investigated using the 24 h recall dietary survey method. The measurements of body composition were performed using BIA (bioelectrical impedance analysis). The potential renal acid load of the diets of athletes (dietary PRAL) and NEAP were calculated. In 10.2% of athletes, NEAP exceeds 100 mEq day−1 and is on average 126.1 ± 32.7 mEq day−1. Higher NEAP in athletes is associated with lower muscle mass (β -1.2% of body weight, p < 0.001) but has no effect on the amount of minerals in the body (β 0.01% of body weight, p = 0.073). Overall, 25–30% of Lithuanian high-performance athletes use high-protein diets (2.0–4.8 g kg−1 day−1) leading to a dietary acid-base imbalance as well as an excessive production of endogenous acids in the body. Athletes are recommended to consume higher amounts of potassium and magnesium. An increase in calcium intake up to 1500 mg per day is recommended. In exceptional cases, periodised nutrition for athletes may involve diets complemented with bicarbonate and/or beta-alanine supplements.

Association of dietary acid-base load and psychological disorders among Iranian women: A cross-sectional study

Metabolic acidosis, which can be affected by dietary acid-base load, seems to be associated with psychological disorders through different pathways. Given limited evidence on dietary acid-base load, we aimed to examine the association of dietary acid-base load with psychological disorders in Iranian women. This cross-sectional study was performed on 447 female subjects (20–50 years old). Dietary intake was assessed using a valid food frequency questionnaire for Iran. Dietary acid-base load was calculated through different indices including potential renal acid load (PRAL), net endogenous acid production (NEAP), and dietary acid load (DAL). To assess psychological disorders, an Iranian validated version of depression, anxiety, and stress scale (DASS-21) was used. The mean value of PRAL, NEAP, and DAL were -8.87mEq/da, 37.94mEq/day, and 30.77mEq/day, respectively. Considering a wide range of confounding variables, compared with the first tertile, a significant positive association was observed between dietary acid-base load and depression (ORPRAL: 3.63; 95 %CI:1.97, 6.71; Ptrend = 0.0001) (ORNEAP:3.42; 95 %CI: 1.87, 6.23; Ptrend = 0.0001) (ORDAL: 3.02; 95 %CI: 1.64, 5.58; Ptrend = 0.0001). Women in the high dietary acid-base load category had higher anxiety (ORPRAL: 3.31; 95 %CI: 1.81, 6.06; Ptrend = 0.0001) (ORNEAP:3.47; 95 %CI: 1.90, 6.33; Ptrend = 0.0001) (ORDAL: 3.25; 95 %CI: 1.76, 5.98; Ptrend = 0.0001). Moreover, there was a strong positive relationship between dietary acid-base load and psychologicaldistress (ORPRAL: 3.79; 95 %CI: 2.09, 6.90; Ptrend = 0.0001) (ORNEAP: 3.67; 95 %CI: 2.04, 6.58; Ptrend = 0.0001) (ORDAL: 3.00; 95 %CI: 1.66, 5.43; Ptrend = 0.0001). Women with higher dietary acid-base load score had greater odds for depression, anxiety, and psychological distress compared to lower ones.

Increased Acid-Producing Diet and Past Smoking Intensity Are Associated with Worse Prognoses Among Breast Cancer Survivors: A Prospective Cohort Study.

Current dietary guidelines do not consider cancer survivors’ and past smokers’ low capacity to regulate their acid–base balance. People with a low capacity to regulate their acid–base balance are more susceptible to acid-producing diets. We studied a cohort of 2950 early stage breast cancer survivors who provided dietary information at baseline and during follow-up. We assessed the intakes of acid-producing diets via two commonly used dietary acid load scores: potential renal acid load (PRAL) and net endogenous acid production (NEAP). We assessed past smoking intensity by pack-years of smoking. After an average of 7.3 years of follow-up, there were 295 total deaths, 249 breast cancer-specific deaths, and 490 cases of recurrent breast cancer. Increased intakes of dietary acid load and pack-years of smoking were each independently and jointly associated with increased total mortality and breast cancer-specific mortality; tests for trends and overall associations were statistically significant for NEAP and marginally significant for PRAL. Compared to women in the lowest tertile of NEAP and pack-year of smoking = 0, women in the highest tertile of NEAP and pack-years of smoking >15 had the greatest increased risk of total mortality (HR = 3.23, 95%CI 1.99–5.26). Further, dietary acid scores were associated with increased breast cancer recurrence among women with pack-years of smoking >0 but not in those with pack-years of smoking = 0 (p values for interactions <0.05). Our study provides valuable evidence for adding dietary acid load scores to dietary guidelines for breast cancer survivors and developing specific guidelines for past smokers among these survivors.

P1625HIGHER DIETARY ACID LOAD IS ASSOCIATED WITH INCREASED RISK FOR KIDNEY FUNCTION DECLINE AND GRAFT FAILURE IN KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Dietary acid load is associated with low grade metabolic acidosis and might accelerate kidney function decline in patients with chronic kidney disease (CKD). We investigated whether dietary acid load, estimated as net endogenous acid production (NEAP), is associated with kidney function decline in kidney transplant recipients (KTR) and to what extent this association is mediated by variation in venous bicarbonate (HCO3-). Method We used data from 642 KTR with a functioning graft ≥1 year after transplantation who were enrolled in the Transplantlines Food &amp; Nutrition Cohort Study between 2008-2011. We applied the Frassetto equation (NEAP = (54.5 X protein (g/d) / potassium (mEq/d) - 10.2)) to calculate NEAPFFQ using intake reported in food frequency questionnaires and NEAPUrine from assessments of 24 hours urinary urea and potassium excretion. Patients were divided into tertiles of NEAP and differences across tertiles were analyzed by ANOVA, Kruskall-Wallis and Chi-Square tests, as appropriate. Cox regression models were used to study the associations between NEAPFFQ and NEAPUrine (both continuous variables and categories) with the composite endpoint kidney function decline, defined as doubling of serum creatinine or graft failure. Mediation analyses were performed to evaluate whether these associations were explained by venous bicarbonate. Results Mean age was 53±13 years, 56.1% were men, and mean eGFR was 52±20 ml/min/1.73m2. Patients within the highest tertile of NEAPFFQ were younger (P=0.04), more recently transplanted (P=0.002), consumed less fruit and vegetables (P&amp;lt;0.001), more fish (P=0.001), less alcohol (P=0.01), more meat (P&amp;lt;0.001) and had lower serum HCO3- concentration (P=0.02). During a median follow-up time of 5.3 (4.1-6.0) years, 121 (18.8%) patients developed kidney function decline. In multivariable Cox regression analysis, higher NEAPFFQ (per SD increase) was associated with increased risk of kidney function decline, independent of potential confounders, including age, sex, BMI, time after transplantation, primary kidney disease, eGFR and proteinuria (adjusted HR 1.30; 95%CI 1.10-1.53, P=0.002). Compared to patients in the lowest NEAPFFQ tertile, those in the highest tertile had a &amp;gt;1.5 higher risk of kidney function decline (adjusted HR 1.67; 95%CI 1.07-2.62, P=0.03). We observed similar results using NEAPUrine as the study exposure (adjusted HR 1.46 per SD increase; 95%CI 1.24-1.73, P&amp;lt;0.001; adjusted HR 1.99; 95%CI 1.24-3.18, P=0.004 for patients in the highest versus lowest tertile of NEAPUrine). These associations between NEAPFFQ (Figure A) and NEAPUrine (Figure B) with kidney function decline were visualized by fitting multivariable Cox regression models based on restricted cubic splines. Mediation analyses estimated that venous HCO3- at baseline mediated 19.3% (P=0.008) of the association between NEAPFFQ and kidney function decline and 26.5% (P=0.002) of the association between NEAPUrine with kidney function decline. Conclusion Higher NEAP is associated with a higher risk for kidney function decline in KTR, and this association was in part mediated by venous HCO3-. We speculate that reducing dietary acid load might mitigate the risk of kidney function decline in KTR.

Association of Dietary Acid Load with the Risk of Insulin Resistance in Middle-Aged and Older Korean Adults

Abstract Objectives Prospective studies on the relationship between diet-induced acid-base imbalance and insulin resistance among Asian populations have been limited. Thus, we investigated weather diet-induced metabolic acidosis was prospectively associated with insulin resistance risk in middle-aged and older Korean adults. Methods A total of 5663 participants from the Korean Genome and Epidemiology Study without type 2 diabetes, insulin resistance, or cancer at baseline were included in this study. To estimate diet-induced metabolic acidosis, we used potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores. They were calculated from the usual dietary intake assessed by a validated 103-item food frequency questionnaire at baseline. Multivariable Cox proportional hazard models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the future risk of insulin resistance after adjusting for covariates. Results During a mean of 7.4-year of follow-up, we documented 3623 insulin resistance cases. In the fully adjusted model, the future risks of insulin resistance were significantly higher among participants in the highest quartiles of PRAL (HR: 1.28, 95% CI: 1.12–1.46, Ptrend = 0.0002) and NEAP (HR: 1.28, 95% CI: 1.12–1.46, Ptrend = 0.0013) compared with those in the lowest. Associations were slightly strengthened among men, adults aged &amp;lt;50 years, those having obesity or low levels of physical activity. Conclusions Diet-induced metabolic acidosis is associated with an increased risk of insulin resistance, irrespective of other type 2 diabetes risk factors. Moreover, we observed effect modifiers of associations between dietary acid load scores and insulin resistance, suggesting stronger effects among men, those aged &amp;lt;50 years, obese individuals, or individuals with low levels of physical activity. Funding Sources None.

Hemoglobin A1c Levels Modify Associations Between Dietary Acid Load and Breast Cancer Recurrence

Abstract Objectives Metabolic acidosis promotes cancer metastasis. No prospective studies have examined the association between dietary acid load and breast cancer recurrence among breast cancer survivors, who are susceptible to metabolic acidosis. Hyperglycemia promotes cancer progression and acid formation; however, researchers have not examined whether hyperglycemia can modify the association between dietary acid load and breast cancer recurrence. Methods We studied 3081 early-stage breast cancer survivors enrolled in the Women's Healthy Eating and Living study who provided dietary information through 24-hour recalls at baseline and during follow-up and had measurements of hemoglobin A1c (HbA1c) at baseline. We assessed dietary acid load using two common dietary acid load scores, potential renal acid load (PRAL) score, and net endogenous acid production (NEAP) score. Results After an average of 7.3 years of follow-up, dietary acid load was positively associated with recurrence when baseline HbA1c levels were ≥5.6% (median level) and ≥5.7% (pre-diabetic cut-point). In the stratum with HbA1c ≥ 5.6%, comparing the highest to the lowest quartile of dietary acid load, the multivariable-adjusted hazard ratio was 2.15 (95%CI 1.34–3.48) for PRAL and was 2.31 (95%CI 1.42–3.74) for NEAP. No associations were observed in the stratum with HbA1c levels were &amp;lt;5.6%. P-values for interactions were 0.01 for PRAL and 0.05 for NEAP. Conclusions Our study demonstrated for the first time that even at or above normal to high HbHbA1c levels, dietary acid load was associated increased risk of breast cancer recurrence among breast cancer survivors. Funding Sources California Tobacco Research Foundation NIH/NCI.

Dietary Acid Load, Smoking Intensity and Total Mortality

Abstract Objectives Former smokers comprise 30–40% among breast cancer survivors. Smoking can cause many biological damages which can still exist in past smokers and make them more susceptible to certain dietary and environmental challenges. Past smokers may have accelerated aging process than never smokers. Limited studies have examined the impacts of dietary acid load total mortality among breast cancer survivors who are never or former smokers. Methods We leveraged an existing cohort, the Women's Healthy Eating and Living (WHEL) Study, which enrolled 3088 women with early stage breast cancer at baseline. This cohort collected dietary information through 24-hour recalls at years 0, 1, and 4, which enabled us to measure dietary acid load accurately and longitudinally. We assessed dietary acid load using two common dietary acid load scores, potential renal acid load (PRAL) score, and net endogenous acid production (NEAP) score. This cohort also assessed past smoking history by pack-years which allowed us to carefully and accurately past smoking intensity. Results In this study, we found that dietary acid load itself was not significantly associated with total mortality among never smokers but significantly associated with total mortality among past smokers who had pack-years &amp;gt;0. When we evaluated the joint impact of dietary acid load and pack-years, women with dietary acid load above median and pack-years ≥15 had 2.38 (95% CI 1.58–3.59) times of risk of total mortality as compared to the reference group (women with dietary acid load below median and pack-years = 0). Conclusions Results from our study will be important for patient care and aid in creating tailored precision nutrition recommendation for breast cancer survivors who are former smoker. Funding Sources University internal funds, NIH/NCI.

Association of Dietary Acid Load with the Prevalence of Metabolic Syndrome among Participants in Baseline Survey of the Japan Multi-Institutional Collaborative Cohort Study

The association between dietary acid load and metabolic syndrome (MetS) has not been fully investigated. A cross-sectional study was performed on 14,042 men and 14,105 women (aged 35–69 years) who participated in a baseline survey of the Japan Multi-Institutional Collaborative Cohort study. Dietary acid load was assessed using the net-endogenous-acid-production (NEAP) score that is closely correlated with the rate of renal net acid excretion. MetS was diagnosed according to the Joint Interim Statement Criteria of 2009 using body-mass index instead of waist circumference. After adjusting for potential confounders, higher NEAP scores were associated with a significantly increased odds ratio (OR) of MetS, obesity, high blood pressure, and high fasting blood glucose. These associations remained significant after further adjustment for carbohydrate intake or two nutrient-pattern scores significantly associated with MetS. After adjustment for fiber, iron, potassium, and vitamin pattern scores, the OR of MetS for the highest quartile of NEAP scores, relative to the lowest quartile, was 1.25 (95% confidence interval 1.12–1.39). There was no significant interaction between sex, age, or body-mass index and NEAP. Higher dietary acid load was associated with a higher prevalence of MetS and several of its components, independently of carbohydrate intake or nutrient patterns.

Association ofdietary acid load with anthropometric indices in children and adolescents.

High dietary acid load (DAL) may have an influence on anthropometric indices. Given that there was no study on the association between DAL and anthropometric indices children and adolescents, the current study was aimed to examine the association between DAL and anthropometric indices in Iranian children and adolescents. Students aged 6-18years were recruited using a multi-stage, cluster sampling method from 30 provinces of Iran. Dietary intake was assessed through a validated food frequency questionnaire. Height (Ht), weight (Wt), neck circumference (NC), waist circumference (WC), wrist circumference, and hip circumference (HC) were measured. WC-to-HC ratio (WHR), WC-to-Ht ratio (WHtR), body mass index (BMI) z-score, tri-ponderal mass index (TMI), and parental BMI were computed. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) were used to estimate DAL. The association between DAL and anthropometric indices was evaluated using linear regression models. In total, 5326 students (46.92% girls), with mean (standard deviations (SD)) age of 12.50 (3.14) years participated in the study (response rate: 98.13%). After adjusting for confounders, there was a significant association between NEAP and NC (P < 0.05). Also, an inverse association was observed between PRAL and NEAP with parental BMI (P < 0.05). Our findings showed a direct association between diet-induced acid load and NC and an inverse association between DAL indices and parental BMI. More well-designed clinical studies are warranted to confirm our results and the underlying mechanisms. Level V, cross-sectional descriptive study.

Hemoglobin A1c Levels Modify Associations between Dietary Acid Load and Breast Cancer Recurrence.

Background: Metabolic acidosis promotes cancer metastasis. No prospective studies have examined the association between dietary acid load and breast cancer recurrence among breast cancer survivors, who are susceptible to metabolic acidosis. Hyperglycemia promotes cancer progression and acid formation; however, researchers have not examined whether hyperglycemia can modify the association between dietary acid load and breast cancer recurrence. Methods: We studied 3081 early-stage breast cancer survivors enrolled in the Women’s Healthy Eating and Living study who provided dietary information through 24-h recalls at baseline and during follow-up and had measurements of hemoglobin A1c (HbA1c) at baseline. We assessed dietary acid load using two common dietary acid load scores, potential renal acid load (PRAL) score and net endogenous acid production (NEAP) score. Results: After an average of 7.3 years of follow-up, dietary acid load was positively associated with recurrence when baseline HbA1c levels were ≥ 5.6% (median level) and ≥5.7% (pre-diabetic cut-point). In the stratum with HbA1c ≥ 5.6%, comparing the highest to the lowest quartile of dietary acid load, the multivariable-adjusted hazard ratio was 2.15 (95% confidence interval [CI] 1.34-3.48) for PRAL and was 2.31 (95% CI 1.42-3.74) for NEAP. No associations were observed in the stratum with HbA1c levels were <5.6%. P-values for interactions were 0.01 for PRAL and 0.05 for NEAP. Conclusions: Our study demonstrated for the first time that even at or above normal to high HbA1c levels, dietary acid load was associated with increased risk of breast cancer recurrence among breast cancer survivors. Impacts: Our study provides strong evidence for developing specific dietary acid load guidelines based on HbA1c levels.

High dietary acid load score is not associated with the risk of metabolic syndrome in Iranian adults.

Background and objective: The association between dietary acid load and metabolic syndrome (MetS) risk is not well-known. Therefore, we aimed to investigate the relationship between dietary acid load and the risk of MetS among Iranian adults. Methods: This cross-sectional study was carried out on 1430 Iranian adults. Dietary intakes were assessed using a validated food frequency questionnaire. Dietary acid load was estimated using potential renal acid load (PRAL) and net endogenous acid production (NEAP). MetS was defined according to the ATP-III criteria. The risk of MetS and its components was explored using logistic regression test. Results: Totally, 205 individuals were identified to have MetS. No significant association for MetS was found across the quartiles of PRAL and NEAP either in the crude model [Q4 PRAL: OR (95% CI): 0.94 (0.67-1.32), and NEAP: OR (95% CI): 0.88 (0.63-1.25)] or fully-adjusted model [Q4 PRAL: OR (95% CI): 0.90 (0.61-1.33), and NEAP: OR (95% CI): 1.05 (0.70-1.57)]. Amongst the components of MetS, higher scores of NEAP was associated with an increased risk of impaired blood sugar after adjustment for potential confounders [OR (95% CI): 1.35 (0.93-1.96)]. No significant association was found for other components either with PRAL or with NEAP. Conclusion: Our findings suggest no association between dietary acid load and MetS risk in Iranian adults. However, higher dietary acid load, measured by NEAP, but not PRAL, was associated with increased risk of impaired fasting blood sugar. Longitudinal studies are warranted to explore whether a diet low in potential acid load could reduce MetS risk.