New and potential properties, characteristics, and analytical methods of ferulic acid: A review

Abstract Phenolic compounds are widely distributed in the plant kingdom and in the microorganisms. Cinnamic acid and its hydroxylated derivative-ferulic acid, are phenolic compounds. Ferulic acid possesses antioxidant potential, as well as anti-cancer, anti-inflammatory, and antimicrobial properties. It prevents the harmful effects of radiation both as an ultraviolet absorber and as a free radical scavenger; it is not cytotoxic. Although ferulic acid has beneficial properties, it is hardly used in cosmetic preparations and has been rarely studied in the literature. Herein, we review the literature on ferulic acid, to provide information which can contribute to further research on the compound.

Dietary acid load and risk of cardiovascular disease: a prospective population-based study.

BACKGROUND AND AIM: Considering the inconsistencies in the cardiovascular effects of dietary acid load and the impact of dietary acidity on the acid-base homeostasis within the body, we aimed to assess the association of dietary acid load and the risk of cardiovascular disease (CVD) in a prospective community-based study. MATERIALS AND METHODS: Participants (n = 2369) free of CVD at baseline (2006-2008) were included from the Tehran Lipid and Glucose Study (TLGS) and followed up for a mean of 6.7 ± 1.4 years. Dietary intakes of the participants were assessed using a semi-quantitative food frequency questionnaire (FFQ). The dietary acid load was evaluated by Potential Renal Acid Load (PRAL) and Net Endogenous Acid Production (NEAP) scores. Both scores have used the macronutrient and micronutrient data of the Food Frequency Questionnaires. Multivariate Cox proportional hazard regression models were used to estimate the 6-years incident risk of CVDs across tertiles of PRAL and NEAP scores. RESULTS: Mean age and body mass index of participants were 38.5 ± 13.3 years and 26.6 ± 4.8 kg/m2 at baseline. Within 6.7 ± 1.4 years of follow-up, 79 cases of cardiovascular events were reported. NEAP was significantly associated with the incidence of CVDs (HRs = 0.50, CI 0.32-0.96; P for trend = 0.032); however, after adjusting for potential confounders, no significant associations were observed between PRAL and NEAP scores and the risk of CVDs. CONCLUSIONS: This study failed to obtain independent associations between dietary acid load and the incidence of CVDs among an Asian population.

Organic Anion-Transporting Polypeptide 1B1/1B3-Mediated Hepatic Uptake Determines the Pharmacokinetics of Large Lipophilic Acids: In Vitro-In Vivo Evaluation in Cynomolgus Monkey.

It is generally presumed that uptake transport mechanisms are of limited significance in hepatic clearance for lipophilic or high passive-permeability drugs. In this study, we evaluated the mechanistic role of the hepato-selective organic anion-transporting polypeptides (OATPs) 1B1/1B3 in the pharmacokinetics of compounds representing large lipophilic acid space. Intravenous pharmacokinetics of 16 compounds with molecular mass ∼400-730 Da, logP ∼3.5-8, and acid pKa <6 were obtained in cynomolgus monkey after dosing without and with a single-dose rifampicin-OATP1B1/1B3 probe inhibitor. Rifampicin (30 mg/kg oral) significantly (P < 0.05) reduced monkey clearance and/or steady-state volume of distribution (VDss) for 15 of 16 acids evaluated. Additionally, clearance of danoprevir was reduced by about 35%, although statistical significance was not reached. A significant linear relationship was noted between the clearance ratio (i.e., ratio of control to treatment groups) and VDss ratio, suggesting hepatic uptake contributes to the systemic clearance and distribution simultaneously. In vitro transport studies using primary monkey and human hepatocytes showed uptake inhibition by rifampicin (100 µM) for compounds with logP ≤6.5 but not for the very lipophilic acids (logP > 6.5), which generally showed high nonspecific binding in hepatocyte incubations. In vitro uptake clearance and fraction transported by OATP1B1/1B3 (ft,OATP1B) were found to be similar in monkey and human hepatocytes. Finally, for compounds with logP ≤6.5, good agreement was noted between in vitro ft,OATP1B and clearance ratio (as well as VDss ratio) in cynomolgus monkey. In conclusion, this study provides mechanistic evidence for the pivotal role of OATP1B-mediated hepatic uptake in the pharmacokinetics across a wide, large lipophilic acid space. SIGNIFICANCE STATEMENT: This study provides mechanistic insight into the pharmacokinetics of a broad range of large lipophilic acids. Organic anion-transporting polypeptides 1B1/1B3-mediated hepatic uptake is of key importance in the pharmacokinetics and drug-drug interactions of almost all drugs and new molecular entities in this space. Diligent in vitro and in vivo transport characterization is needed to avoid the false negatives often noted because of general limitations in the in vitro assays while handling compounds with such physicochemical attributes.

Activation of p21 limits acute lung injury and induces early senescence after acid aspiration and mechanical ventilation.

The p53/p21 pathway is activated in response to cell stress. However, its role in acute lung injury has not been elucidated. Acute lung injury is associated with disruption of the alveolo-capillary barrier leading to acute respiratory distress syndrome (ARDS). Mechanical ventilation may be necessary to support gas exchange in patients with ARDS, however, high positive airway pressures can cause regional overdistension of alveolar units and aggravate lung injury. Here, we report that acute lung injury and alveolar overstretching activate the p53/p21 pathway to maintain homeostasis and avoid massive cell apoptosis. A systematic pooling of transcriptomic data from animal models of lung injury demonstrates the enrichment of specific p53- and p21-dependent gene signatures and a validated senescence profile. In a clinically relevant, murine model of acid aspiration and mechanical ventilation, we observed changes in the nuclear envelope and the underlying chromatin, DNA damage and activation of the Tp53/p21 pathway. Absence of Cdkn1a decreased the senescent response, but worsened lung injury due to increased cell apoptosis. Conversely, treatment with lopinavir and/or ritonavir led to Cdkn1a overexpression and ameliorated cell apoptosis and lung injury. The activation of these mechanisms was associated with early markers of senescence, including expression of senescence-related genes and increases in senescence-associated heterochromatin foci in alveolar cells. Autopsy samples from lungs of patients with ARDS revealed increased senescence-associated heterochromatin foci. Collectively, these results suggest that acute lung injury activates p53/p21 as an antiapoptotic mechanism to ameliorate damage, but with the side effect of induction of senescence.

Dietary Acid Load and Relationship with Albuminuria and Glomerular Filtration Rate in Individuals with Chronic Kidney Disease at Predialysis State.

The Western diet, characterized by excessive consumption of animal protein and reduced intake of vegetables and fruits, is also rich in sulfur, chlorine, and organic acids, which are the main sources of dietary acid load. A relationship between dietary acid load, renal function, and progression of chronic kidney disease has been demonstrated. Dietary modifications seem to contribute to a reduction in dietary acid load, and are associated with improved outcomes in individuals with chronic kidney disease (CKD). The aim of this paper was to review the existing evidence concerning the association between dietary acid load and renal function in nondialyzed individuals with CKD. A systematic review was conducted by gathering articles in electronic databases (MEDLINE/PubMed, Scopus, and Web of Science) from January 2018 to May 2021. Dietary acid load and GFR and/or albuminuria were analyzed. A total of 1078 articles were extracted, of which 5 met the inclusion criteria. Only one study found no statistically significant associations between the study variables. The remaining showed a negative association between dietary acid load and renal function. This systematic review confirmed the existence of an association between dietary acid load and renal function, with a high dietary acid load contributing to a decreased renal function.

Effects of Replacing In-feed Antibiotics with Synergistic Organic Acids on Growth Performance, Health, Carcass, and Immune and Oxidative Statuses of Broiler Chickens Under Clostridium perfringens Type A Challenge.

This study was conducted to investigate the effects of replacing in-feed antibiotics with synergistic organic acids on growth performance, health, carcass, and immune and oxidative statuses of broiler chickens under Clostridium perfringens (CP) type A challenge. Two organic acid products were tested: organic acid 1 (OA1), consisting of butyrate, medium-chain fatty acids, organic acids, and phenolics; and organic acid 2 (OA2), consisting of buffered short-chain fatty acids. Six hundred 1-day-old male Arbor Acres broiler chicks were randomly assigned to one of five treatments: Control 1, basal diet, nonchallenged birds; Control 2, basal diet, with CP challenge; antimicrobial growth promoters (AGP), basal diet supplemented with Aureomycin (chlortetracycline), with CP challenge; OA1, basal diet supplemented with OA1, with CP challenge; and OA1OA2, basal diet supplemented with OA1 and OA2, with CP challenge. Each treatment had eight replicate pens of 15 birds. The experiments lasted for 29 days. The disease challenge was performed on days 15-17, with an oral gavage of 0.5 mL of CP culture (2.0 × 108 colony-forming units [CFU]/mL) for each bird. Body weights (BWs), intestinal lesion scores, immune organ indices, and serum malondialdehyde (MDA) concentrations were measured on days 19, 22, and 29, respectively, in three birds per pen. Carcass characteristics were determined on day 29. No treatment-related differences in mortality were noted before (P = 0.28) or after (P = 0.64) challenge or over the whole study period (days 0-28; P = 0.66). On day 19, the BW of Control 2 was lower than other treatments (P < 0.0001). On day 22, AGP, OA1, and OA1OA2 had higher BW than Control 2 (P = 0.001). The breast muscle yield of OA1 and OA1OA2 was higher than AGP (P < 0.05). The abdominal fat yield of OA1OA2 was lower than AGP and Control 2 (P < 0.05). On day 22, the birds fed OA1OA2 showed lower intestinal lesion scores than OA1 (P < 0.05). No treatment-related differences in immune organ (spleen, thymus, and bursa) indices were noted (P > 0.05). On day 29, the MDA concentration of OA1 and OA1OA2 was lower than those of Control 1 and AGP (P < 0.05). In conclusion, the addition of organic acids may protect broiler chickens from severe intestinal lesions and oxidative stress and may help reduce abdominal fat mass deposition. There is potential for organic acid-based products as alternatives for AGP in preventing necrotic enteritis in broilers.

Effect of Replacing In-Feed Antibiotics with Synergistic Organic Acids, with or without Trace Mineral and/or Water Acidification, on Growth Performance and Health of Broiler Chickens Under a Clostridium perfringens Type A Challenge.

This study investigated the effects of a proprietary commercial feed additive (FA) comprised of a blend of fatty acids, organic acids, and phytochemicals; a hydroxychloride copper (MA); as well as a water acidification product (WA), alone and in combination, on growth performance in nonvaccinated broiler chickens raised in an antibiotic-free production system. The test treatments were FA; WA; FA and WA combined (FA + WA); and FA, WA, and MA combined (FA + WA + MA). The efficacy of these treatments was compared with a negative control (CON) and a medicated feeding program (bacitracin, antibiotic growth promoter [AGP]). Ross 708 cockerels (n = 2376) were subject to a 3-phase commercial feeding program, namely, starter (0-20 days), grower (21-28 days), and finisher (28-35 days), with no coccidiostats or additional medications added to the feed. On day 14, birds were subjected to an in-feed Clostridium perfringens challenge and a subset of animals were euthanized and the ileal digesta was collected for C. perfringens enumeration. Prior to pathogen challenge (day 14), birds fed the FA + WA and F + WA + MA treatments had significantly higher body weights (+2.6%-3.5%) than those fed CON and similar body weights to birds fed the AGP. These early growth advantages were not sustained postchallenge. Clostridia counts in ileal digesta were dramatically reduced in birds fed the AGP compared with all treatments. The FA (-2.5 log), FA + WA (-2.0 log), and FA + WA + MA (-2.3 log) treatments had significantly lower clostridia counts than the CON treatment. Together, these findings support the use of combined in-feed and in-water strategies for reducing clostridia, while maintaining growth, in antibiotic-free production systems.

A randomised oral fluoride retention study comparing intra-oral kinetics of fluoride-containing dentifrices before and after dietary acid exposure.

OBJECTIVE: This exploratory, randomised, single-blind, crossover, study evaluated fluoride and calcium ion concentrations and pH following use of one of two 1450 ppm fluoride (NaF), 5% w/w KNO3 dentifrices: (1) test dentifrice (with cocamidopropyl betaine) with an orange juice (OJ) rinse; (2) test dentifrice with a deionized (DI) water rinse or (3) comparator dentifrice (with sodium lauryl sulphate and tetrasodium pyrophosphate) with an OJ rinse. DESIGN: Eighteen participants used their assigned dentifrice, rinsed with DI water, then expectorate was collected. Sixty min post-brushing, participants rinsed with OJ or DI water then expectorate was collected. Saliva samples were collected pre-brushing and at 1, 5, 10, 15, 30 and 60 min post-brushing and following the 60 min OJ/DI water rinse. The pH of samples was taken. RESULTS: Significant differences (p < 0.05) were found in salivary fluoride ion concentrations between test and comparator dentifrices at 30 and 60 min and following the 60 min OJ rinse, favouring the former. Significant differences were also found between test and comparator dentifrices for salivary calcium ion concentration at 1, 5 and 10 min (p < 0.0001), favouring the former, and between test or comparator + OJ rinse and test + water rinse (p < 0.005), favouring the latter. No pH differences were shown prior to OJ/water rinse. Products were generally well-tolerated. CONCLUSIONS: Results confirmed that acid-labile fluoride is released from the oral cavity following a dietary acid challenge and showed that formulation excipients may impact on retention of such.

Higher dietary acid load is not associated with risk of breast cancer in Iranian women.

BACKGROUND: Dietary acid load (DAL) may play a key role in certain cancers, including breast cancer (BC); however, evidence showing a causal relationship is lacking. AIM: We examined the relationship between DAL, assessed with both the potential renal acid load (PRAL) and the net endogenous acid production (NEAP) scores, and BC risk. METHODS: We identified 150 women who had a diagnosis of BC recently and 150 age-matched apparently healthy controls. Data from dietary intake and anthropometric measures were collected from participants and eventually, PRAL and NEAP scores were obtained from nutrient intakes. Multivariate odds ratios (OR) with 95% confidence intervals (CI) were used to evaluate the relationship of BC risk with PRAL and NEAP scores. RESULTS: The odds ratios (OR) of BC according to tertiles of PRAL and NEAP scores by multivariate logistic regression models revealed that both PRAL (P-trend = 0.8) and NEAP (P-trend = 0.1) scores were not significantly associated with BC risk. After controlling confounders, multiple logistic regressions still remained non-significant which indicated no significant associations between PRAL (P-trend = 0.9), NEAP (P-trend = 0.4) scores and risk of BC. CONCLUSION: The results of our study suggested that there is no significant relationship between DAL and BC incidence among Iranian women.

Effects of low molecular weight organic acids on Cu accumulation by castor bean and soil enzyme activities.

Chelating agents have been considered as an important phytoremediation strategy to enhance heavy metal extraction from contaminated soil. A pot experiment was conducted to explore the effects of low molecular weight organic acids (LMWOAs) on the phytoremediation efficiency of copper (Cu) by castor bean, and soil enzyme activities. Results indicated that the addition of all the three kinds of LMWOAs (citric, tartaric, oxalic acids) did not decrease the biomass of castor bean, despite the fact they reduced the concentration of chlorophyll-a in leaves compared to the control. The Cu concentrations in the roots and shoots significantly increased by 6-106% and 5-148%, respectively, in the LMWOAs treatments so that the total accumulation of Cu by whole plants in all the LMWOAs treatments increased by 21-189% in comparison with the control. The values of the translocation factor (TF) and bio-concentration factor (BCF) of Cu in castor bean also rose following the addition of LMWOAs, indicating that the LMWOAs enhanced the uptake and transportation of Cu. Moreover, the application of LMWOAs did not significantly change the soil pH but significantly increased the activity of soil enzymes (urease, catalase, and alkaline phosphatase). The addition of exogenous LMWOAs increased the available Cu significantly in the soil, thus promoted the phytoextraction efficiency of Cu by castor bean. These results will provide some new insights into the practical use of LMWOAs for the phytoremediation of heavy-metal-contaminated soil employing castor bean.

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.

Increased dietary calcium inclusion in fully acidified prepartum diets improved postpartum uterine health and fertility when fed to Holstein cows.

The objective of this study was to determine the effects of prepartum negative dietary cation-anion difference diet (DCAD) fed at two dietary Ca inclusion rates on postpartum uterine health and ovulation dynamics of multiparous Holstein cows (n = 76). Treatments began at 28 days before expected calving until parturition and were: CON: DCAD = +6 mEq/100g of DM with low dietary Ca (46.2 ± 15.2 g Ca/d; 0.4% DM; n = 26); ND: DCAD = -24 mEq/100g of DM with low dietary Ca (44.1 ±â€¯16.1 Ca/d; 0.4% DM; n = 24); NDCA: DCAD = -24 mEq/100g of DM with high dietary Ca (226.6 ±â€¯96.0 g Ca/d; 2.0% DM; n = 26). Vaginal discharge was evaluated through the fresh period via Metricheck (MC) for presence of purulent material. Polymorphonuclear (PMN) cell concentration in the uterus was evaluated at 15 and 30 days relative to calving (DRC). Endometrial tissue was harvested at 30 DRC for glandular morphology, presence of tight-junctions and adheren-junctions proteins, as well as assessment of superoxide dismutase (SOD) and glutathione peroxidase (GPX) activity. Blood plasma and serum samples were harvested in the prepartum and postpartum phase and were assessed for concentrations of lipopolysaccharide binding protein (LBP), serum amyloid A (SAA), and haptoglobin (HP). Ovarian dynamics were assessed through the fresh period until first timed artificial insemination (TAI). Cows fed CON had a lower MC score (P = 0.06) than the average of cows fed ND and cows fed NDCA. Cows fed ND had a higher MC score than cows fed NDCA. Cows fed NDCA had greater uterine gland epithelial height (P = 0.02) than cows fed ND. Cows fed NDCA also had a greater number of epithelial cells per gland (P = 0.05) than cows fed ND. Cows fed NDCA had greater intensity of occludin expression (P = 0.15) than cows fed ND. Cows fed NDCA had increased activity of SOD (P = 0.05) and decreased activity of GPX (P < 0.001) than cows fed ND. Cows fed ND had higher plasma HP concentrations than cows fed NDCA in the prepartum (P = 0.01) and post-partum (P = 0.03) periods. Cows fed ND and NDCA had lower (P = 0.01) postpartum plasma HP concentration than cows fed CON. In conclusion, cows fed NDCA had an improved uterine environment most likely due to alleviation of oxidative stress, an enhanced immune response to parturition and uterine discharge comparable to cows fed CON.

Dietary acid load, blood pressure, fasting blood sugar and biomarkers of insulin resistance among adults: Findings from an updated systematic review and meta-analysis.

OBJECTIVES: There is no clear summarised report of the association between dietary acid load components including potential renal acid load (PRAL) and net-endogenous acid production (NEAP) with cardiometabolic risk factors. In the current meta-analysis, we aimed to systematically review and summarise the eligible observational studies evaluating the association between PRAL and NEAP with blood pressure and hypertension and markers of glucose haemostasis among adults. DESIGN AND SETTING: In a systematic search from PubMed, SCOPUS, Web of Sciences and Cochrane electronic databases up to May 2019, relevant studies were included in the literature review. Observational studies evaluating the association between PRAL and NEAP with the systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), haemoglobin A1 C (HbA1 C), HOMA-ß and quantitative insulin check index (QUICKI) and also prevalence or odds of hypertension, hyperglycaemia and diabetes were included. RESULTS: Total number of studies included in the 14 separate meta-analyses were as follows: Mean (SD) of SBP (PRAL, n = 12; NEAP, n = 6), mean (SD) of DBP (PRAL, n = 8; NEAP, n = 3), mean (SD) of FBS (PRAL, n = 12; NEAP, n = 5), mean (SD) of HbA1 C (PRAL, n = 6; NEAP, n = 4), mean (SD) of HOMA-IR (PRAL, n = 7), mean (SD) of insulin (PRAL, n = 7; NEAP, n = 2); OR of type 2 diabetes mellitus (T2 DM) (PRAL, n = 8; NEAP; n = 6), HTN prevalence (PRAL, n = 9; NEAP, n = 9), T2 DM prevalence (PRAL, n = 7; NEAP, n = 6). According to our results, being in the highest PRAL categories was associated with higher SBP (WMD = 0.98; CI: 0.51, 1.45; P < .001), DBP (WMD = 0.61; CI: 0.089, 1.135; P = .022), insulin (WMD = -0.235, CI: 0.070, 0.400; P = .005), higher odds of diabetes (OR = 1.19; CI: 1.092, 1.311; P < .001), higher prevalence of T2 DM (13% and 11% in highest vs lowest category). While, being in the highest category of NEAP was only associated with higher odds of diabetes (OR = 1.22; CI: 1.14, 1.31, P < .001). In subgroup analysis for finding the possible source of heterogeneity, the continent, dietary assessment tool, sample size and gender were the potent sources of heterogeneity. No association between PRAL and NEAP with HbA1 C, HOMA-IR was reported. CONCLUSIONS: In the current meta-analysis, we found potent negative effects of high dietary acid load particularly higher PRAL scores cardiometabolic risk factors. Therefore, lower acidogenic food ingredients in the diets are suggested for the prevention of cardiovascular risk factors and diabetes.

Optimization of cosmetic formulations development using Box-Behnken design with response surface methodology: physical, sensory and moisturizing properties

Considering the importance of an adequate composition of the formulation in the development of stable, safe and effective cosmetic products, experimental design techniques are tools that can optimize the formulation development process. The objective of this study was to develop topical formulations using the Box-Behnken design with response surface methodology and evaluate its physical, sensory and moisturizing properties. The experimental design used in the first step allowed to identify and to quantify the influence of raw materials, as well as the interaction between them. In the second step, the analysis identified the influence of soy lecithin, the phytantriol and capric acid triglyceride and caprylic on the consistency index, stickiness and greasiness and skin hydration. Cetearyl alcohol, dicetyl phosphate and cetyl phosphate 10EO and acrylates/C10-30 alkylacrylate crosspolymer showed effects in rheological parameters. The addition of soy lecithin had significant effects in terms of consistency index, stickiness, oiliness and immediate moisturizing effects. Phytantriol showed effects on increasing consistency index and oiliness sensation. Thus, the experimental design was shown to be an effective tool for research and development of cosmetics, since it allowed the assessment of the individual and interaction effects of raw materials in the responses: rheological parameters, sensory and clinical efficacy.

Effects of iso-α-acids, the hop-derived bitter components in beer, on the MRI-based Brain Healthcare Quotient in healthy middle-aged to older adults.

AIM: Neurological disorders are a major public health issue worldwide and are often associated with structural changes in the brain. We have previously demonstrated that iso-α-acids (IAAs), the hop-derived bitter components in beer, improve memory impairment in aged and Alzheimer's disease mouse models. In this study, we evaluated the effects of IAA intake on the brain structure in healthy middle-aged to older adults. This study was conducted under the Impulsing Paradigm Change through Disruptive Technologies Program (ImPACT) study launched by the Cabinet office of Japan. METHOD: This study employed an open-labeled, single-arm, before and after design. Healthy middle-aged to older adults consumed a beverage containing IAAs (3 mg/190 mL) for 4 weeks.Recently developed magnetic resonance imaging-based brain health indicators were used to evaluate the following brain conditions: the Brain Healthcare Quotient (BHQ) based on gray matter volume (GM-BHQ) and white matter fractional anisotropy (FA-BHQ). RESULTS: In total, 25 subjects were recruited, and GM-BHQ and FA-BHQ were measured before and after intervention. In all subjects, no significant differences in GM-BHQ and FA-BHQ were observed. In subjects aged ≥ 60 years (mean 54.5; standard deviation 3.9) (n = 8), GM-BHQ was significantly increased 4 weeks after intervention compared with that before intervention. CONCLUSION: Intake of beverages containing IAAs might affect brain aging, particularly in healthy older adults, which may prevent the development of neurological disorders. Future studies employing more robust designs can elucidate the effects of IAAs on GM-BHQ and cognitive functions.

Dietary Acid Load: A Novel Nutritional Target in Overweight/Obese Children with Asthma?

Obesity has been repeatedly linked to asthma, and several potential mechanisms have been proposed in the etiologies of the obese-asthma phenotype. Considering that lungs play an important role in systemic pH and acid-base regulation, are a key organ in asthma development, and that nutritional inadequacy of several nutrients and high dietary acid load can affect airway inflammation and reactivity, we aimed to test the hypothesis that dietary acid load may be associated with asthma in children. Data on 699 children (52% females), aged 7-12 years, were analyzed. Anthropometric measurements were performed to assess body mass index. Dietary acid load was calculated using potential renal acid load (PRAL) equations from a 24 h dietary recall administrated to children. Adjusted PRAL for total energy intake was applied with the use of the residual method. Lung function and airway reversibility were assessed with spirometry. Asthma was defined by a positive bronchodilation or self-reported medical diagnosis with reported symptoms (wheezing, dyspnea, or dry cough) in the past 12 months. After adjustment for energy intake, sex, age, parent's education level, and physical activity, positive and significant associations were found between asthma and PRAL [odds ratio (OR) = 1.953, 95% CI = 1.024, 3.730) in overweight/obese children. Our findings suggest that dietary acid load might be a possible mechanism in overweight/obese-asthma phenotype development.

Elevated hypertension risk associated with higher dietary acid load: A systematic review and meta-analysis.

BACKGROUND & AIMS: The association between dietary acid load and hypertension risk is inconclusive. We conducted a systematic review and meta-analysis to summarize effect of dietary acid load on blood pressure. METHODS: A comprehensively search was performed in electronic databases including EMBASE, PubMed, Web of Science and Chinese National Knowledge Infrastructure. Summary ORs and their corresponding 95% CIs were computed assuming a randomized model or fixed model. RESULTS: Ten publications comprising 4 cohort and 6 cross-sectional studies were eligible for meta-analysis. There were 8 studies about potential renal acid load (PRAL) and 4 about net endogenous acid production (NEAP). Essential hypertension was statistically associated with higher PRAL (OR = 1.14, 95% CI = 1.02-1.17). Our findings also demonstrated a positive impact of higher PRAL on elevating both diastolic pressure (WMD = 0.96, 95% CI = 0.67-1.26) and systolic pressure (WMD = 1.57, 95% CI = 1.12-2.03). A 35% increased risk of hypertension associated with higher NEAP was identified (OR = 1.35, 95% CI = 1.03-1.78). CONCLUSIONS: The current study suggests that dietary acid load might be potential risk factor of hypertension.

Destruction of the Dorsal Motor Nucleus of the Vagus Aggravates Inflammation and Injury from Acid-Induced Acute Esophagitis in a Rat Model.

BACKGROUND/AIMS: The aim of this study is to examine the protective effect of the cholinergic anti-inflammatory pathway (CAP) in experimental esophagitis in rats. METHODS: A total of 40 male Sprague-Dawley (SD) rats were randomly divided into five groups as follows: control group, sham + saline group, sham + acid group, operation + saline group, and operation + acid group. Two weeks after the dorsal motor nucleus of the vagus (DMV) destruction, hydrochloric acid with pepsin was perfused into the lower part of the esophagus for 90 min. The rats were sacrificed 60 min after perfusion. The esophagus was prepared for hematoxylin and eosin (HE) staining, and the degree of inflammation and NF-κB activation in the esophagus was measured. Inflammatory cytokines (TNF-α, IL-6, IL-1ß, and PGE2) in the esophagus were measured by ELISA. The brain was removed and processed for c-fos immunohistochemistry staining. The c-fos-positive neurons were counted and analyzed. RESULTS: The TNF-α, IL-1ß, IL-6, and PGE2 concentrations in the esophageal tissue increased after acid perfusion. The microscopic esophagitis scores and the activation of NF-κB p65 in the esophagus were significantly higher in the operation + acid group than in the operation + saline group. c-fos-positive neurons significantly increased in rats receiving acid perfusion in the amygdala (AM), the paraventricular nucleus of the hypothalamus (PVN), the parabrachial nucleus (PBN), the nucleus of the solitary tract (NTS)/DMV, the nucleus ambiguous (NA), the reticular nucleus of the medulla (RNM), and the area postrema (AP). After DMV destruction, c-fos expression was reduced in the AM, PVN, PBN, NTS/DMV, NA, RNM, and AP, especially in the AM, PVN, NTS/DMV, RNM, and AP. CONCLUSIONS: The DMV is an important nucleus of the CAP. The DMV lesion can aggravate esophageal inflammation and injury from acid-induced acute esophagitis in a rat model. The CAP has a protective effect on the acute esophagitis rat model and could be a new therapy for reflux esophagitis (RE).

Effects of encapsulated essential oils and organic acids on laying performance, egg quality, intestinal morphology, barrier function, and microflora count of hens during the early laying period.

The objective of this study was to investigate the effect of encapsulated essential oils and organic acids (EOA) on the growth performance, egg quality, intestinal morphology and functions, and microbial count of laying hens from week 21 to 30. A total of five hundred and four 21-wk-old layers were randomly allotted into 4 groups consisting of 7 replicates with 18 birds per replicate. The birds were fed a basic diet (CON) or diets with EOA at 150 mg/kg, 300 mg/kg, and 450 mg/kg in the other 3 groups, respectively. Compared to the CON group, the addition of 150 mg/kg EOA significantly increased laying rate (P < 0.05) of hens from week 21 to 25. A linear increasing (linear, P < 0.01) in ileal villus height of laying hens fed EOA from 150 to 300 mg/kg was observed at week 30. At week 25, the supplementation of 300 mg/kg EOA significantly increased (P < 0.05) mRNA relative expression of aminopeptidase, sodium-glucose cotransporter 1, and Na+-independent neutral amino acid transporter in duodenum and glucose transporter 2 in jejunum of laying hens compared to the CON groups. Meanwhile, the relative expression of glucose transporter 2 mRNA in the jejunum was upregulated with increasing concentration of EOA in diets (linear, P < 0.05). Hens in EOA 300 group had higher mRNA relative expression of mucin-2 in ileum (P < 0.05) than hens in CON group. Additionally, the secretory immunoglobulin in ileum A were linear decreased (linear, P < 0.01) with the increasing supplement of EOA. Dietary supplementation with EOA tended to increase (P = 0.083) the counts of Bifidobacterium in cecal digesta at week 25 and 30. In conclusion, dietary with EOA may maintain intestinal tract morphology and promote digestive and absorptive capacities and barrier function, especially at 300 mg/kg. This study provided evidence of using EOA as a potential feed additive for laying hens.

In-feed resin acids reduce matrix metalloproteinase activity in the ileal mucosa of healthy broilers without inducing major effects on the gut microbiota.

The chicken gut is constantly exposed to harmful molecules and microorganisms which endanger the integrity of the intestinal wall. Strengthening intestinal mucosal integrity is a key target for feed additives that aim to promote intestinal health in broilers. Recently, dietary inclusion of resin-based products has been shown to increase broiler performance. However, the mode of action is still largely unexplored. Coniferous resin acids are known for their anti-microbial, anti-inflammatory and wound-healing properties, all properties that might support broiler intestinal health. In the current study, the effect of pure resin acids on broiler intestinal health was explored. Ross 308 broilers were fed a diet supplemented with coniferous resin acids for 22 days, after which the effect on both the intestinal microbiota as well as on the intestinal tissue morphology and activity of host collagenases was assessed. Dietary inclusion of resin acids did not alter the morphology of the healthy intestine and only minor effects on the intestinal microbiota were observed. However, resin acids-supplementation reduced both duodenal inflammatory T cell infiltration and small intestinal matrix metalloproteinase (MMP) activity towards collagen type I and type IV. Reduced breakdown of collagen type I and IV might indicate a protective effect of resin acids on intestinal barrier integrity by preservation of the basal membrane and the extracellular matrix. Further studies are needed to explore the protective effects of resin acids on broiler intestinal health under sub-optimal conditions and to elaborate our knowledge on the mechanisms behind the observed effects.