High Acid Load Research Articles

Epidemiologic Evidence for Association between a High Dietary Acid Load and the Breast Cancer Risk

Background and Purpose: Dietary acid load contributes to metabolic acidosis, leading to inflammation and cell transformation, potentially implicated in cancer development. Albeit an increased risk of recurrence among BC survivors was reported for a high acid load, the epidemiologic evidence associating diet-dependent acid load and cancer risk, particularly for breast cancer (BC), is still very limited. Therefore, we have explored in the present study its role in BC risk. Methods: A case-control study was performed on 1461 patients (572 BC cases and 889 age-frequency matched controls), through a multi-topic questionnaire, which included a food frequency questionnaire. Food-derived nutrients were calculated from available databases. The dietary acid load was calculated based on existing measures as potential renal acid load (PRAL) score and net endogenous acid production (NEAP) score. Odds Ratios (ORs) and their 95% confidence intervals were estimated by logistic regression, adjusting for potential confounders. Results: We found direct associations between dietary acid load and BC risk. Both scores were significantly associated (OR=2.46 and OR=1.78 for highest PRAL and NEAP, respectively). A positive BC family history involved higher risks (OR=6.14 and OR=3.38 for highest PRAL and NEAP, respectively). Linear trends were found in all overall and stratified analyses. Conclusions: Results suggest that a low acid load dietary style may reduce BC risk since both PRAL and NEAP scores were directly associated with meat intake and inversely associated with plant-based foods intake. The findings agree with studies focused on food groups and dietary patterns. Further studies are needed to confirm these findings. Doi: 10.28991/SciMedJ-2021-0302-8 Full Text: PDF

Dietary Acid Load and Blood Pressure in Healthy Adults

Mild metabolic acidosis, as influenced by dietary intake, has been the topic of many epidemiological studies as a contributing factor to developing high blood pressure (BP). Diets that include an abundance of fruits and vegetables are marked by a high potassium intake that contributes to a decreased renal acid load. In contrast, a Western diet, which is typically deficient in potassium and higher in protein and phosphorus, is characterized by a higher acid load that may negatively alter acid-base balance and contribute to future cardiovascular events. The purpose of this study was to investigate the relation between dietary acid load and BP in healthy adults. Healthy adults aged 18-79 years old were included in this retrospective analysis. Dietary acid load was approximated using the Potential Renal Acid Load (PRAL), which is strongly influenced by dietary intake of protein, phosphorus and potassium assessed from a 3-day diet record. The average of three seated BP measurements was used for our analysis. Associations between PRAL and BP were determined using bivariate and partial Pearson correlations. One hundred and fifty-four subjects (78M/76W; 39 ± 2 yrs; BMI 25 ± 0.3 kg/m²) were included in this study. Men had a higher BMI (26 ± 1 kg/m² vs. 25 ± 1 kg/m²; p=0.03) and BP (119 ± 1/70 ± 1 vs. 111 ± 2/67 ± 1 mmHg; p<0.05) than women. Average PRAL was 13.4 ± 1.6 mEq/day and is consistent with a high protein and low potassium diet. PRAL values were also greater in men than women (18.6 ± 2.6 mEq/day vs. 8.1 ± 1.8 mEq/day; p<0.05). Total energy intake was 2089 ± 48 kcals/day, with men consuming more energy than women (2340 ± 70 kcals/day vs. 1835 ± 51 kcals/day; p<0.001). PRAL was positively associated with systolic BP (SBP) and pulse pressure (PP) (SBP: r=0.171, p=0.034; PP: r=0.261, p=0.001) but not with diastolic BP (DBP: r=-0.050, p=0.539). When sex and age were included as covariates, PRAL was positively correlated with both SBP and PP (SBP: r=0.205, p=0.011; PP: r=0.234, p=0.004) but not DBP (DBP: r=0.007, p=0.936). In conclusion, these findings indicate that a higher dietary acid load, correlates with a higher SBP and PP. This relation remains even after accounting for age and sex.

The Association Between Dietary Acid Load and Odds of Migraine: A Case-Control Survey.

IntroductionIt has been shown that a high acid load in the human body can affect inflammatory factors and the nitric oxide pathway. These factors are also thought to play an important role in the initiation of migraine attacks. We have therefore explored the association between dietary acid load and odds of migraine in a case–control study.MethodsThe migraine group (n = 514, diagnosed according to the International Classification of Headache Disorders 3rd edition [ICHDIII] criteria) was recruited from a tertiary headache clinic. The controls consisted of 582 sex-matched healthy volunteers who were randomly selected from the general population. A validated 168-item semiquantitative food frequency questionnaire was used for dietary intake assessments. Estimation of the dietary acid load was performed using three different measures: potential renal acid load (PRAL) score, net endogenous acid production (NEAP) score, and protein/potassium ratio.ResultsMultivariable logistic regression analysis showed that, in comparison with the lowest tertile, the highest tertile of dietary acid load measures, including PRAL (odds ratio [OR] 7.208, 95% confidence intervals [CI] 3.33–15.55), and NEAP (OR 4.108, 95% CI 1.924–8.774) scores and the protein/potassium ratio (OR 4.127, 95% CI 1.933–8.814), significantly increased the odds of migraine (P value for trend ≤ 0.001).ConclusionIn this study, high dietary acid load was associated with higher odds of migraine. It is therefore possible that restricting dietary acid load could reduce the odds of migraine in susceptible subjects. However, due to the preliminary nature of the current evidence, caution is advised in drawing a definitive conclusion. More well-designed studies are required for a better understanding of this important issue.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40120-021-00247-2.

Dopamine-Grafted Hyaluronic Acid Coated Hyperbranched Poly(β-Amino Esters)/DNA Nano-Complexes for Enhanced Gene Delivery and Biosafety

Gene therapy has attracted particular attention for the treatment of various genetic diseases, and the development of gene delivery vectors is of utmost importance for in vivo applications of gene drugs. Various cationic polymers with high nucleic acid loading and intracellular transfection efficiency have been reported, however, their biological applications are limited by potential toxicity. Surface modification is a robust solution to detoxify the cationic vectors, but this can inevitably weaken the transfection efficiency. To address this dilemma, we reported the ability of a dopamine (DA)-grafted hyaluronic acid (HA) to modify gene vectors for enhanced gene delivery and biosafety. The nano-vector was formed by using branched poly(β-amino esters) (PAEs), and surface coating with HA-DA to form a core-shell nano-structure via electrostatic attraction. Upon HA-DA modification, the biosafety of the gene delivery vehicle was improved, as demonstrated by the cell cytotoxicity assay and hemolysis test. Notably, the nano-system displayed a DA-dependent transfection efficiency, in which a higher DA grafting degree resulted in better efficacy. This can be explained by the adhesive nature of DA, facilitating cell membrane interaction, as well as DA receptor mediated active targeting. At the optimal DA grafting ratio, the nano-system achieved a transfection efficiency even better than that of commonly used polyethylenimine (PEI) vectors. Together with its excellent biocompatibility, the vector presented here holds great promise for gene delivery applications.

Sinapic Acid Loaded Secondary Growth of SiO2–Au Core Shell Nanostructure as an Effective Antiarthritic Agent to Treat Collagen-Induced Arthritis

Systemic autoimmune disease of rheumatoid arthritis (RA) is a severe case of joint deformity. Serious off-targeted drugs are not capable of curing RA and lead to increased risk of infection. Nanoparticles-based arthritis therapy is a promising approach to promote effective treatment strategy in inflammatory tissues. In particular, an inorganic-metal hybrid form of core–shell nanostructure has a significant role in the drug application due to its unique properties arising from either core or shell materials. Presently, the Au–SiO2 core–shell nanomaterials with an average diameter of 78 nm were successfully synthesized. The nanomaterials revealed a very high sinapic acid (SA) loading to eliminate the inflammatory response in RA by avoiding the side effects of conventional drugs. Various characterization techniques revealed that the as-fabricated Au–SiO2 has a higher-contrast core and aggregates of SiO2 on their surfaces/of the shell. Besides, Au–SiO2 core–shell exhibits the large extended pore structure to store a large quantity of SA drugs. Then, the mice were treated with different doses of SA loaded Au–SiO2 core–shell to assess the various biochemical parameters, including body weight, arthritic score analysis, hind paw volume, organ indices measurement, histological analysis pro-inflammatory cytokines, and anti-serum antibody analysis. The obtained results have proven that SiO2–Au develop a core–shell skin structure and each with its unique SA loading might act as a potential anti-inflammatory agent, which can be effectively used to treat collagen-induced arthritis compared to Au–SiO2 and SA. Therefore, SA loaded Au–SiO2 core–shell nanomaterials might employ as an interesting candidate in future arthritis applications.

Long Term Effects of Forest Liming on the Acid-Base Budget

In Rhineland-Palatinate (Germany), a high percentage of the forest area is located on poor soils with low buffering capacity. Extensive liming applications were performed to compensate for the negative consequences of acid deposition. In 1988, three experimental sites with untreated control plots and different liming treatments were established in coniferous stands to investigate the effectiveness of liming on acidification and its effect on forest ecosystems. Measuring deposition and seepage waters for 24 years allowed for calculating long-term acid-base budgets. The original approach was expanded by data from a detailed sampling of the forest stand and mineral weathering rates. Without liming, the acid load exceeded the buffer capacity by base cation release from silicate weathering during the whole observation period. As a result, there was a high release of aluminum. After liming seepage water output of organic anions, nitrate and sulfate increased in some cases, leading to a higher acid load. However, the carbonates of dolomitic limestone compensated for a higher acid load, resulting in less aluminum released compared to the control plots. Until sulfate output by seepage water declines and nitrogen emissions are reduced, liming and restricted biomass harvesting are required for forest stands on base poor soils to prevent further acidification, decline of nutrient stocks, and the destruction of clay minerals.

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.

Ultrasonically-mediated one-pot synthesis of substituted imidazoles via sulfamic acid functionalized hollow magnetically retrievable solid-acid catalyst

In this work, we report the synthesis of functionalized hollow magnetite spheres (HMS) which were synthesized through gas-bubble assisted Ostwald ripening approach and post-functionalized with sulfamic acid groups. The fabricated material was used as an efficient solid-acid catalyst for one-pot three-component synthesis of medicinally important tri-substituted imidazoles under ultrasonic irradiation. Some of the striking features of the present protocol over existing routes are environmentally benign synthesis, milder reaction conditions, excellent yields, high selectivity, short reaction times, use of ultrasound as green energy source, less waste generation and effortless magnetic recovery and recycling of the catalyst. Further, the synthesized magnetite spheres extend the scope of ‘double functionalization’, i.e., the acidic groups can be immobilized on both internal and external surfaces which provides high acid loading as compared to previously reported solid supports.

Effect of acidic MCM-41 mesoporous silica functionalized with sulfonic acid groups catalyst in conversion of methanol to dimethyl ether

The global issue of contamination and power reserves has given dimethyl ether (DME) considerable attention. It is an encouraging and clean green material for the future resulting from its clean combustion properties. In this paper, a novel MCM-41-propyl-SO3H catalyst was successfully prepared with tethering of the active sulfonic acid groups onto the support via covalent bonds. This material was investigated as catalyst for DME synthesis via methanol dehydration in a fixed bed flow reactor at different experimental settings. TGA, NH3-TPD, SEM, XRD and BET techniques​ were utilized to characterize the synthesized material. MCM-41 sulfonated catalyst showed great thermal stability, high surface area and significant acid loading. The catalytic tests also demonstrated that the maximum methanol conversion was observed at 350 °C and catalyst contact time of 8 s. In addition, the catalyst showed a total selectivity to DME; light hydrocarbons and higher oxygenated compounds were not formed at temperatures above 300° C.

The effect of body acid-base state and manipulations on body glucose regulation in human.

Long-term exposure to high dietary acid load has been associated with insulin resistance and type 2 diabetes in epidemiological studies. However, it remains unclear whether the acid load of the diet translates to mild metabolic acidosis and whether it is responsible for the impairment in glucose regulation in humans. Previously, in a cross-sectional study we have reported that dietary acid load was not different between healthy individuals with normal weight and those with overweight/obesity, irrespective of insulin sensitivity. However, 4-week high acid load diet increased plasma lactate (a small component of the anion gap) and increased insulin resistance in healthy participants. The change in plasma lactate correlated significantly with the change in insulin resistance. Because cause-and-effect could not be evaluated in these settings, we sought to directly test the effect of an alkalizing treatment preload on postprandial glucose regulation. In a randomized placebo-controlled study with a crossover design, we administered sodium bicarbonate (NaHCO3, 1.68 g) prior to high acid load meal to healthy individuals. We found that while the bicarbonate preload attenuated the post meal decrease in pH observed with placebo, no effect on postprandial glucose regulation (glucose, insulin, and C-peptide) was observed. Following 3-month treatment of nondiabetic individuals with bicarbonate, others have reported no change in insulin resistance markers, consistent with our findings. Together, studies in human suggest that insulin resistance associated with longstanding obesogenic diet may be mediated by mild metabolic acidosis. However, buffering the Western diet with bicarbonate and increasing body pH does not change glucose homeostasis in nondiabetic individuals. Further studies are required to shed light on the role of body acid-base balance and glucose homeostasis in health and disease.

Dietary acid load in children with chronic kidney disease.

Western diet is characterized by a high acid load that could generate various degrees of metabolic acidosis, of which at least the stronger forms are known to contribute to the progression of chronic kidney disease (CKD). The aim of this study was to estimate the potential renal acid load (PRAL) and acid base status in CKD patients attended at the Children's Hospital J.M. de los Ríos in Caracas, Venezuela from April 2015 to February 2016. Twenty-seven children with CKD were included. Diet composition was evaluated by a food frequency questionnaire and a 24-h intake reminder. PRAL was calculated by the Remer and Manz method. Laboratory tests included serum creatinine, electrolytes and venous gases. Protein intake was above recommendations in 21 patients (78.6%). Average vegetable and fruit intake was 0.4 and 1.5 servings per day, respectively. Mean PRAL was 16 ± 10.7 mEq/day. PRAL correlated positively with energy (p = 0.005), protein (p = 0.001) and fat intake (p = 0.0001), daily servings of dairy (p = 0.04) meat (p = 0.001) and cereals (0.001) and negatively with vegetable intake (p = 0.04). Serum pH and bicarbonate were 7.3 ± 0.08 and 20.46 ± 4.5 mEq/L, respectively. Twenty-one patients (80.7%) with metabolic acidosis were treated with sodium bicarbonate. Dietary pattern of Venezuelan children with CKD may constitute a risk factor for the progression of the disease by promoting metabolic acidosis via unfavorable dietary acid loads. PRAL should be assessed as a valuable guide for nutritional counseling in children with CKD.

Acid Loading Unmasks Glucose Homeostatic Instability in Proximal-Tubule-Targeted Insulin/Insulin-Like-Growth-Factor-1 Receptor Dual Knockout Mice.

Metabolic syndrome and type 2 diabetes are associated with some degree of acidosis. Acidosis has also been shown to upregulate renal gluconeogenesis. Whether impaired insulin or insulin-like-growth factor 1 receptor (IGF1) signaling alter this relationship is not known. Our aim was to determine the effects of deletion of insulin and IGF1 receptors (Insr and Igf1r) from renal proximal tubule (PT) on the gluconeogenic response to acidosis. We developed a mouse model with PT-targeted dual knockout (KO) of the Insr/Igf1r by driving Cre-recombinase with the gamma-glutamyl transferase (gGT) promoter. Male and female mice were maintained as control or acidotic by treatment with NH4Cl in the drinking water for 1-week. Acidosis in both genotypes increased renal expression of phosphoenolpyruvate carboxykinase (PEPCK) and fructose-1-bisphosphatase (FBP1), but not glucose-6-phosphatase catalytic subunit (G6PC), which showed significantly lower expression in the KO regardless of treatment. Several differences between KO and WT suggested a protective role for insulin/IGF1 receptor signaling in maintaining relative euglycemia in the face of acidosis. First, the increase in FBP1 with acid was greater in the KO (significant interactive term). Secondly, proximal-tubule-associated FOXO1 and AKT overall protein levels were suppressed by acid loading in the KO, but not in the WT. Robust intact insulin signaling would be needed to reduce gluconeogenesis in PT. Third, phosphorylated FOXO1 (pS256) levels were markedly reduced by acid loading in the KO PT, but not in the WT. This reduction would support greater gluconeogenesis. Fourth, the sodium-glucose cotransporter (SGLT1) was increased by acid loading in the KO kidney, but not the WT. While this would not necessarily affect gluconeogenesis, it could result in increased circulatory glucose via renal reabsorption. Reduced susceptibility to glucose-homeostatic dysregulation in the WT could potentially relate to the sharp (over 50%) reduction in renal levels of sirtuin-1 (SIRT1), which deacetylates and regulates transcription of a number of genes. This reduction was absent in the KO. Insulin resistance of the kidney may increase whole-body glucose instability a major risk factor for morbidity in diabetes. High dietary acid loads provide a dilemma for the kidney, as ammoniagenesis liberates α-ketoglutarate, which is a substrate for gluconeogenesis. We demonstrate an important role for insulin and/or IGF1 receptor signaling in the PT to facilitate this process and reduce excursions in blood glucose. Thus, medications and lifestyle changes that improve renal insulin sensitivity may also provide added benefit in type 2 diabetes especially when coupled with metabolic acidosis.

Influence of Medications Containing Acid Salts on Serum Bicarbonate in CKD

Many medications are formulated with acid salts. Their effect on acid-base balance in CKD is unclear. We calculated the acid load (meq/d) from medications prescribed to 74 United States veterans with diabetes and CKD to identify agents with high potential acid load. We also determined cross-sectional associations between the acid load from medications and acid-base parameters after adjusting for demographics, eGFR, protein intake, and other confounders. Of the 125 medications prescribed, 31 (25%) contained an acid salt. Metformin hydrochloride (15.4 meq/d at 2550 mg/d) and gabapentin hydrochloride (13.0 meq/d at 2700 mg/d) were identified as agents with a high potential acid load. Mean daily acid load from medications was 6.6 meq/d in the overall cohort, 14.2 meq/d in the high medication acid load group (≥7.7 meq/d, n=29), and 1.6 meq/d in the low medication acid load group (<7.7 meq/d, n=45). After adjusting for potential confounders, those in the high acid load group had 1.7 meq/L lower total carbon dioxide (CO2) and 2.2 meq/L higher anion gap than those in the low acid load group. Use of gabapentin alone was not associated with differences in total CO2 or anion gap. Use of metformin alone was associated with 0.7 meq/L lower total CO2 and 1.0 meq/L higher anion gap. Use of metformin with gabapentin was associated with 1.8 meq/L lower total CO2 and 2.4 meq/L higher anion gap. The higher anion gap was not explained by higher serum lactate levels. The acid load from medications was not associated with differences in urinary ammonium, titratable acid, or pH. Medications containing acid salts, particularly metformin hydrochloride and gabapentin hydrochloride, are sources of an exogenous acid load. These agents may influence serum total CO2 levels and serum anion gap in individuals with CKD. Investigations of the Optimum Serum Bicarbonate Level in Renal Disease, NCT01574157.

Recent Advances in Nanomaterials with Inherent Optical and Magnetic Properties for Bioimaging and Imaging-Guided Nucleic Acid Therapy.

Nucleic acid therapy is and will continue to be of great interest in cancer treatment. The development of nanocarriers with high nucleic acid loading capacity, low toxicity, and specific targeting, with excellent pharmacokinetic/pharmacodynamic profiles, will enable us to realize safe and effective nucleic acid therapy. Tremendous efforts have been directed toward the production of optimized theranostic nanocarriers that can simultaneously provide treatment and real-time monitoring to aid researchers and physicians in making adaptation strategies during early drug development and patient's treatment, respectively. In this review, several nanomaterials with inherent optical and magnetic properties, developed for bioimaging and imaging-guided nucleic acid therapies, are introduced and discussed. In each subsection, the unique characteristics of the corresponding theranostic nanomaterials are reviewed and discussed with examples. Finally, we present the remaining challenges that must be addressed and provide our opinions on the future of nanomaterial medicines for bioimaging and imaging-guided nucleic acid therapy.

Cortisol and 11 beta-hydroxysteroid dehydrogenase type 2 as potential determinants of renal citrate excretion in healthy children.

In patients with Cushing disease, renal citrate excretion is reduced. A low urinary citrate concentration is a risk factor for nephrolithiasis. Since higher acid loading is one major determinant of reduced citrate excretion, we aimed to examine whether glucocorticoids still within the physiological range may already impact on urinary citrate excretion independently of acid-base status. Overall, 132 healthy prepubertal participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study who had collected two successive 24-h urine samples (at 1 and 2 years) before the start of their pubertal growth spurt were included in the study. Net acid excretion capacity (NAEC), urinary potential renal acid load (PRAL), creatinine, calcium, and various cortisol metabolites were measured in all samples. Glucocorticoid quantification was done by GC-MS and radioimmunoassay. In regression models multivariable-adjusted for 24-h urinary PRAL, NAEC, creatinine and calcium, urinary free cortisol (UFF), 6β-hydroxycortisol, and 20α-dihydrocortisol showed significant inverse relationships (P ≤ 0.02) with 24-h renal citrate output. By contrast, the estimate of renal 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), i.e., the ratio of urinary free cortisone/UFF, associated positively with urinary citrate (P = 0.04). In line with studies in hypercortisolic state, even moderately high cortisol levels in healthy children, still within the physiological range, may negatively impact on the kidney's citrate excretion. Besides, a higher 11β-HSD2 activity, favoring cortisol inactivation, is paralleled by an increased citrate excretion.

Functionalized mesoporous silica as matrix for shape-stabilized phase change materials

Shape-stabilized phase change materials (ssPCM) are used to reversibly store thermal energy while keeping their macroscopic solid shape. A porous matrix, such as mesoporous silica, can be used to obtain ssPCM through impregnation. However, a non-melting interface layer is formed between the matrix and heat storage component, which severely reduces the available pore volume and the energy storage capacity of the composite. We studied functionalization of mesoporous silica as a strategy for engineering the non-melting layer and improving the heat storage of the resulting composites. Stearic acid was used as the active heat storage phase and mesocellular foam silica as the porous matrix. Phenyl and methyl groups were found to increase the nanoconfined phase enthalpy. The non-melting layer volume is similar to unfunctionalized silica, suggesting that methyl and phenyl groups are present inside the non-melting layer. Carboxylic acid functionalization decreases the layer volume, yielding the highest enthalpy of the nanoconfined phase, of 34.5 J/g. This value is 15% higher than the nanoconfined enthalpy of materials containing unfunctionalized silica. Total heat storage values of 130 J/g were obtained for PCM samples containing phenyl or carboxylic acid functionalized matrices. The functionalized materials show high stearic acid loading (72–79 wt%), shape-stability and constant thermal response over 200 heating-cooling cycles. A facile method for assessing the non-melting layer volume is provided. The study shows that suitable surface functionalization can suppress the non-melting layer formation, providing a path for enhancing the heat storage potential of shape-stabilized PCM containing mesoporous silica matrices.

Prediagnostic Plasma Bile Acid Levels and Colon Cancer Risk: A Prospective Study.

Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans. Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations. Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (ORquartile 4 vs quartile 1= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95%CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk. This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.

Diet-Dependent Acid Load-The Missing Link Between an Animal Protein-Rich Diet and Nonalcoholic Fatty Liver Disease?

Our group recently showed that animal protein was independently associated with nonalcoholic fatty liver disease (NAFLD). We hypothesize that this may be explained by a high diet-dependent acid load [dietary acid load (DAL)]. This cross-sectional study is embedded in a prospective population-based cohort. We estimated DAL proxies via food-frequency questionnaires using potential renal acid load (PRAL; using dietary protein, phosphorus, potassium, calcium, and magnesium intake), net endogenous acid production (NEAP; using protein and potassium intake), and the animal protein-to-potassium ratio (A:P). We defined NAFLD using ultrasound after excluding secondary steatogenic causes. We used logistic regression models-adjusted for sociodemographic, lifestyle, and metabolic traits-on categorized [quartile (Q)1 to 4] and continuous DAL proxies (allowing for nonlinearity) and NAFLD. We included 3882 participants, of which 1337 had NAFLD. All DAL proxies were higher, meaning more acidic, in individuals with NAFLD (PRAL, -2.9 vs -5.5 mEq/d; NEAP, 37.0 vs 35.1 mEq/d; and A:P, 13.3 vs 12.4; all P < 0.001). The highest Q of DAL proxies was associated with NAFLD independent of sociodemographic and lifestyle confounders, but significance dissipated after correction for metabolic confounders and multiple testing. However, the P value for nonlinearity was significant in all DAL proxies (P < 0.001). Natural cubic splines performed better with than without DAL proxies in the fully adjusted model (all P ≤ 0.038). The highest probability of NAFLD was found for an acidic diet. This study showed an independent nonlinear association between an acidic diet and NAFLD. Further studies with acid-base biomarkers are needed, but our findings might provide a mechanistic explanation for the harmful association between an animal protein-rich diet and NAFLD.

Can diet acidity reflect diet quality index in healthy children and adolecents?

Rationale: It is very important to provide internal balance in optimal growth in children. Foods often consumed by children such as sugar, chocolate, hamburger, crisps, have high acid load and energy content. When the body's buffering systems are insufficient to balance this acid load, chronic metabolic acidosis can occur and growth and development can be affected. Few studies have been published on the dietary acid load in healthy children. The aim of this study was to calculate the diet acid load and show its association with diet quality in healthy school-aged children and adolescents.

Arylether-type polybenzimidazoles bearing benzimidazolyl pendants for high-temperature proton exchange membrane fuel cells

Phosphoric acid-doped polybenzimidazole membranes offer great potential for high-temperature proton exchange membrane applications due to their high proton conductivity at high-temperature and low-humidity conditions. However, it remains a major challenge in fabricating high-performance membranes with both high proton conductivity and good mechanical strength. Here, a series of polybenzimidazoles with increased imidazole groups are obtained by incorporating some benzimidazole groups onto an arylether-type polybenzimidazole backbone via a simple and efficient N-substituted reaction without catalyst. This arylether-type polybenzimidazole is verified to exhibit good solubility under extremely high molecular weight, and it provides the possibility for fabricating the high mechanical strength membranes at high phosphoric acid doping levels. It is of interest to find that the introduction of additional bulky benzimidazole moieties even enhance the mechanical strength of the membranes, and at the same time, significantly improve their acid doping levels, acid doping rate and proton conductivity. Importantly, the acid-doped grafted membranes show superior dimensional-mechanical stability even at high acid loading. With an acid doping level of 22.1, the grafted membrane displays a high conductivity of 212 mS cm−1 at 200 °C without humidification. A H2/O2 fuel cell based on this membrane has a peak power density of 443 mW cm−2 at 160 °C.