Effective doses and risks from medical diagnostic x-ray examinations for male and female patients from childhood to old age.

The consideration of risks from medical diagnostic x-ray examinations and their justification commonly relies on estimates of effective dose, although the quantity is actually a health-detriment-weighted summation of organ/tissue-absorbed doses rather than a measure of risk. In its 2007 Recommendations, the International Commission on Radiological Protection (ICRP) defines effective dose in relation to a nominal value of stochastic detriment following low-level exposure of 5.7 × 10-2Sv-1, as an average over both sexes, all ages, and two fixed composite populations (Asian and Euro-American). Effective dose represents the overall (whole-body) dose received by a person from a particular exposure, which can be used for the purposes of radiological protection as set out by ICRP, but it does not provide a measure that is specific to the characteristics of the exposed individual. However, the cancer incidence risk models used by ICRP can be used to provide estimates of risk separately for males and females, as a function of age-at-exposure, and for the two composite populations. Here, these organ/tissue-specific risk models are applied to estimates of organ/tissue-specific absorbed doses from a range of diagnostic procedures to derive lifetime excess cancer incidence risk estimates; the degree of heterogeneity in the distribution of absorbed doses between organs/tissues will depend on the procedure. Depending on the organs/tissues exposed, risks are generally higher in females and notably higher for younger ages-at-exposure. Comparing lifetime cancer incidence risks per Sv effective dose from the different procedures shows that overall risks are higher by about a factor of two to three for the youngest age-at-exposure group, 0-9 yr, than for 30-39 yr adults, and lower by a similar factor for an age-at-exposure of 60-69 yr. Taking into account these differences in risk per Sv, and noting the substantial uncertainties associated with risk estimates, effective dose as currently formulated provides a reasonable basis for assessing the potential risks from medical diagnostic examinations.

Factors influencing parental trust in medical researchers for child and adolescent patients' clinical trial participation.

Parental trust in medical researchers is a commonly cited barrier to their child's participation in clinical research. Yet, there is little understanding of factors influencing parental trust to be implemented in interventions to address their concerns. This study seeks to identify psychosocial and modifying factors influencing parental trust in medical researchers to improve child and adolescent patients clinical trial participation, and potentially their health outcomes. We conducted a cross-sectional study with 307 parents. Multiple ordinary linear (OLS) regression was conducted to determine: (1) psychosocial and modifying factors associated with parental trust; and (2) perceived advantages and disadvantages associated with parental trust. Parent's race (White) (ß = .343, p < .001), higher education level (ß = .409, p < .001), higher perceived advantages of adolescent clinical trials (ß = .142, p < .001), and lower perceived disadvantages of adolescent clinical trials (ß = -.337, p = .001) were the most significant predictors of higher levels of parental trust in medical researchers. Parents who were African American and had lower education levels expressed lower levels of trust in medical researchers. Education on the benefits of clinical trials could reduce parents' apprehension towards their child's participation in clinical trials. Results support the development of a clinical trial education program for parents to improve their trust in medical researchers.

Prognostic Factors in Pediatric Sport-Related Concussion.

PURPOSE OF REVIEW: Sport-related concussion (SRC) and mild traumatic brain injury (mTBI) have been thrust into the national spotlight, with youth athletes bearing the burden of this public health problem. The current review aims to provide a practical summary of pediatric SRC, including key terminology, return to play/school, and risk factors for post-concussion syndrome (PCS). RECENT FINDINGS: While the majority of youth athletes recover within 2 to 4 weeks, approximately 10% of athletes experience a protracted recovery with symptoms lasting months, impacting social, scholastic, and sporting activities. In the pediatric population, the strongest predictors of PCS are initial symptom burden and prior concussion, with mixed results behind the factors of gender, headaches, and learning disability. The role of psychiatric, family history, sports, and socioeconomic factors remain in their infancy.

Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions.

Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non-periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non-dental plaque biofilm-induced gingival diseases and dental plaque-induced gingivitis. Non-dental plaque biofilm-induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque-induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque-induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non-periodontitis patient or in a currently stable "periodontitis patient" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient-centered approach to care, and therefore, creates differences in the way in which a "case" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations.

Influences of Gender, Religion, Dietary Patterns, and Mixed-sex Education on Aggressiveness in Children: A Sociodemographic Study in Municipal Primary Schools of South Delhi.

BACKGROUND: Increasing antisocial and violent behaviors in adolescents and young adults present serious challenges for public health. Children with persistent high levels of aggressiveness are often associated with developing conduct disorders later in life. Early detection of highly aggressive children and sociodemographic risk-modifying factors are important for developing effective preventive strategies. OBJECTIVES: The present study was undertaken to assess levels of aggressiveness for detecting highly aggressive children in sample populations of primary school children in an urban setting and determine significant biosociocultural risk-modifying factors in this scenario. METHODS: The study was conducted during August-September, 2015 in 5 primary schools of South Delhi Municipal Corporation. Sociodemographic data on 2080 students were collected. Overall aggressiveness scores (OA-Scores) were estimated using a self-report questionnaire in Hindi. RESULTS: Categorizing students according to their OA-Scores, the data revealed that highly aggressive children constituted 4.3% of the study population. Analysis showed significant influence of (a) gender: boys displayed higher levels of aggressiveness compared to girls; (b) dietary pattern: omnivores showed higher aggressiveness than vegetarians; and (c) school environment: boys in mixed-sex (coeducational) schools displayed lower aggressiveness than from single-sex schools. Statistically significant influences of religion (Hindu/Muslim) and family type (joint/nuclear) on aggressiveness profiles were not noticeable. CONCLUSIONS: Vegetarian diets and mixed-sex education act as protective factors in the development of aggressiveness in children, especially among boys. Extending investigations to populations differing in geography and cultural backgrounds are warranted to verify present results.

Clinical and biochemical heterogeneity between patients with glycogen storage disease type IA: the added value of CUSUM for metabolic control.

OBJECTIVE: To study heterogeneity between patients with glycogen storage disease type Ia (GSD Ia), a rare inherited disorder of carbohydrate metabolism caused by the deficiency of glucose-6-phosphatase (G6Pase). STUDY DESIGN: Descriptive retrospective study of longitudinal clinical and biochemical data and long-term complications in 20 GSD Ia patients. We included 11 patients with homozygous G6PC mutations and siblings from four families carrying identical G6PC genotypes. To display subtle variations for repeated triglyceride measurements with respect to time for individual patients, CUSUM-analysis graphs were constructed. RESULTS: Patients with different homozygous G6PC mutations showed important differences in height, BMI, and biochemical parameters (i.e., lactate, uric acid, triglyceride, and cholesterol concentrations). Furthermore, CUSUM-analysis predicts and displays subtle changes in longitudinal blood triglyceride concentrations. Siblings in families also displayed important differences in biochemical parameters (i.e., lactate, uric acid, triglycerides, and cholesterol concentrations) and long-term complications (i.e., liver adenomas, nephropathy, and osteopenia/osteoporosis). CONCLUSIONS: Differences between GSD Ia patients reflect large clinical and biochemical heterogeneity. Heterogeneity between GSD Ia patients with homozygous G6PC mutations indicate an important role of the G6PC genotype/mutations. Differences between affected siblings suggest an additional role (genetic and/or environmental) of modifying factors defining the GSD Ia phenotype. CUSUM-analysis can facilitate single-patient monitoring of metabolic control and future application of this method may improve precision medicine for patients both with GSD and remaining inherited metabolic diseases.

Electromobility Shift Assay Reveals Evidence in Favor of Allele-Specific Binding of RUNX1 to the 5' Hypersensitive Site 4-Locus Control Region.

In our previous studies on the Iranian ß-thalassemia (ß-thal) patients, we identified an association between the severity of the ß-thal phenotype and the polymorphic palindromic site at the 5' hypersensitive site 4-locus control region (5'HS4-LCR) of the ß-globin gene cluster. Furthermore, a linkage disequilibrium was observed between this region and XmnI-HBG2 in the patient population. Based on this data, it was suggested that the well-recognized phenotype-ameliorating role assigned to positive XmnI could be associated with its linked elements in the LCR. To investigate the functional significance of polymorphisms at the 5'HS4-LCR, we studied its influence on binding of transcription factors. Web-based predictions of transcription factor binding revealed a binding site for runt-related transcription factor 1 (RUNX1), when the allele at the center of the palindrome (TGGGG(A/G)CCCCA) was A but not when it was G. Furthermore, electromobility shift assay (EMSA) presented evidence in support of allele-specific binding of RUNX1 to 5'HS4. Considering that RUNX1 is a well-known regulator of hematopoiesis, these preliminary data suggest the importance of further studies to confirm this interaction and consequently investigate its functional and phenotypical relevance. These studies could help us to understand the molecular mechanism behind the phenotype modifying role of the 5'HS4-LCR polymorphic palindromic region (rs16912979), which has been observed in previous studies.

[Factors modifying cord blood IgE levels - a pilot study]. / Faktory modifikujúce koncentráciu IgE v pupocníkovej krvi - pilotná stúdia.

AIM: The complex influence of internal and external environmental factors on the individual and his/her immune system and the lack of suitable markers to assess and reduce the risk of the development of allergies during the lifetime can explain the continuous increase in the number of people affected by some form of allergy. According to the results of some studies, cord blood IgE level could be a useful early marker for assessing the risk of atopic diseases, but the studies showed controversial results. In addition, several authors discuss the origin of these antibodies (synthesis in utero, peripartum contamination from maternal blood or placental transfer). The aim of our pilot study was to investigate the possible influence of modifying factors on cord blood IgE level. MATERIAL AND METHODS: Our group of patients consisted of 184 retrospectively selected neonates (98 boys, 53.3% and 86 girls, 46.7%) from whom cord blood was collected and cord blood IgE level was measured 25 years ago (PRIST method). The impact of selected modifying factors (sex, type of delivery or month of birth) on cord blood IgE level was assessed retrospectively. RESULTS: Higher cord blood IgE levels were found in boys than in girls, in neonates born by Caesarean section than in those born by natural delivery, and in those born in the winter months than in other seasons of the year. Our findings are in agreement with those of other authors. CONCLUSION: Based on our results and those of others, we assume that the selected factors affect the cord blood IgE levels to varying degrees. These facts should be taken into consideration while interpreting the cord blood IgE levels.

Data quality and relevance in ecotoxicity: The undocumented influences of model assumptions and modifying factors on aquatic toxicity dose metrics.

A model-based approach using hypothetical organic chemicals examines how aquatic toxicity test results are influenced by toxicity modifying factors such as hydrophobicity, exposure duration, body size, lipid content, mode of toxic action (via Critical Body Residue differences), and metabolic degradation. Differences of up to one to three orders of magnitude were identified for modeled LC50s. Dominance of CBR by low log Kow chemicals can cause further influences. Such differences cause significant changes in the relationship between exposure- and organism-based doses and create substantial difficulties for both interpretation of test results and extrapolation to other laboratory or field exposure conditions. The resulting variability is not readily evident in toxicity testing as insufficient data are collected to validate fundamental assumptions. Consequently, results obtained with standard aquatic toxicity test protocols do not yield consistent, comparable measures of relative toxicity and are inappropriate for quantitative toxicology and risk applications. The substantial uncertainties in testing results created by such undocumented variability must also be given serious consideration in data quality and relevance assessments. Necessary improvements in aquatic toxicity testing methodology should include explicit estimation of toxicokinetics and toxicodynamics and routine validation of toxicological model assumptions.

Variability of hemoglobin F expression in hemoglobin EE disease: hematological and molecular analysis.

Although the molecular basis of variability of hemoglobin (Hb) F has been extensively examined in ß-thalassemia and sickle cell diseases, less study has been done on Hb E disorder. To address the variability of Hb F expression in Hb EE disease, we have examined multiple single nucleotide polymorphisms (SNPs) in the ß-globin gene cluster, BCL11A and HBS1L-MYB genes and determined their associations with Hb F levels in this syndrome. Study was done on 141 adult Thai individuals with homozygous Hb E. Hematological parameters were recorded and Hb F measured using Hb-HPLC analyzer. It was found in 26 cases that co-inheritance of α-thalassemia could lead to significant lower production of Hb F. Association of Hb F expression with the (G)γ-Xmn I polymorphism and other SNPs including rs2297339, rs2838513, rs4895441 and rs9399137 in HBS1L-MYB gene and rs4671393 and rs11886868 in BCL11A gene was therefore analyzed in the remaining 115 cases without α-thalassemia. It was found that 4 of these 7 SNPs including (G)γ-XmnI polymorphism (rs7482144), HBS1L-MYB (rs4895441) and (rs9399137) and BCL11A (rs4671393) were significantly associated with higher proportions of subjects with high Hb F (Hb F≥5%). The result demonstrated that multiple genetic modifying factors including T allele of (G)γ-XmnI polymorphism (rs7482144), G allele of HBS1L-MYB (rs489441), C allele of HBS1L-MYB (rs9399137) and C allele of BCL11A (rs4671393) are associated with increased Hb F and in combination could explain approximately 80% of the variation of Hb F in Hb EE disease in Thai population. Other genetic factors regulating Hb F expression in this common genetic disorder remains to be elucidated.

Identifying important life stages for monitoring and assessing risks from exposures to environmental contaminants: results of a World Health Organization review.

In this paper, we summarize exposure-related issues to consider in determining the most appropriate age ranges and life stages for risk assessment. We then propose a harmonized set of age bins for monitoring and assessing risks from exposures to chemicals for global use. The focus is on preconception through adolescence, though the approach should be applicable to additional life stages. A two-tiered set of early life age groups is recommended. The first tier involves the adoption of guidance similar to the childhood age groups recommended by the U.S. Environmental Protection Agency, whereas the second tier consolidates some of those age groups to reduce the burden of developing age-specific exposure factors for different regions. While there is no single "correct" means of choosing a common set of age groups to use internationally in assessing early life exposure and risk, use of a set of defined age groups is recommended to facilitate comparisons of potential exposures and risks around the globe, the collection of data and analyses of aggregate exposure and cumulative risk. Application of these age groups for robust assessment of exposure and risk for specific populations will require region-specific exposure factors as well as local environmental monitoring data.

Combining biomarkers of susceptibility with toxicodynamic models: a novel approach for assessing modifying factors.

Biomarkers of susceptibility are indicative of an individual's capacity to react to particular exposures, whereas toxicodynamic models elucidate the correlation between exposure and response. In this article, a novel methodology is presented for the evaluation of modifying factors in the field of toxicology. The proposed approach involves the integration of biomarkers of susceptibility with toxicodynamic models. Through the integration of these two methodologies, scientists are able to gain a more comprehensive understanding of the impact of modifying factors, such as genetic polymorphisms or epigenetic profiles, on an individual's reaction to toxic substances. This methodology has the potential to facilitate a more thorough evaluation of the hazards linked to the contact with combinations of chemicals and the cumulative effects of such exposures. The utilization of biomarkers in the evaluation of exposure for risk assessment is progressively incorporating the examination of susceptibility factors alongside exposure factors. This may involve the identification of a particular genetic polymorphism for a metabolic enzyme. The integration of ecotoxicological tests with models is crucial for achieving a comprehensive assessment. This approach exhibits the potential to enhance our comprehension of disease causation and facilitate the identification of populations that may exhibit an elevated susceptibility to disease.

Development and Validation of Multiple Linear Regression Models for Predicting Chronic Zinc Toxicity to Freshwater Microalgae.

Multiple linear regression (MLR) models were developed for predicting chronic zinc toxicity to a freshwater microalga, Chlorella sp., using three toxicity-modifying factors (TMFs): pH, hardness, and dissolved organic carbon (DOC). The interactive effects between pH and hardness and between pH and DOC were also included. Models were developed at three different effect concentration (EC) levels: EC10, EC20, and EC50. Models were independently validated using six different zinc-spiked Australian natural waters with a range of water chemistries. Stepwise regression found hardness to be an influential TMF in model scenarios and was retained in all final models, while pH, DOC, and interactive terms had variable influence and were only retained in some models. Autovalidation and residual analysis of all models indicated that models generally predicted toxicity and that there was little bias based on individual TMFs. The MLR models, at all effect levels, performed poorly when predicting toxicity in the zinc-spiked natural waters during independent validation, with models consistently overpredicting toxicity. This overprediction may be from another unaccounted for TMF that may be present across all natural waters. Alternatively, this consistent overprediction questions the underlying assumption that models developed from synthetic laboratory test waters can be directly applied to natural water samples. Further research into the suitability of applying synthetic laboratory water-based models to a greater range of natural waters is needed. Environ Toxicol Chem 2023;42:2630-2641. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Association between physical activity and depressive symptoms in adolescents: A prospective cohort study.

It remains uncertain whether a protective association between physical activity and depression exists among adolescents and what the optimal level of physical activity might be. This study aimed to estimate the associations of physical activity levels with depressive symptoms and new-onset depression, while identifying potential modifying factors influencing the relationships. In this cohort study, we initially enrolled 1957 participants at baseline and followed up with 1738 of them after two years. Our analysis focused on data from 1482 students who provided complete information on both physical activity and depressive symptoms. Generalized linear regression and restricted cubic spline regression models were performed. Our adjusted models revealed that engaging in 4-7 h/week of moderate-to-vigorous physical activity (MVPA) at baseline was negatively associated with subsequent depressive symptoms and new-onset depression compared to the non-MVPA group. However, exceeding 7 h/week of MVPA did not provide substantial benefits. Furthermore, drinking and screen time potentially modified the relationship between MVPA and new-onset depression. Our findings suggest that 4-7 h of MVPA per week may be an appropriate level to reduce depressive symptoms in adolescents. Moreover, individual behaviors (e.g., drinking and screen time) warrant heightened attention in interventions targeting the reduction of depression in this population.

Factors Influencing the Efficacy of COVID-19 Vaccines: A Quantitative Synthesis of Phase III Trials.

To date, there is still a paucity of data from Phase III trials concerning the efficacy of vaccines against COVID-19. Furthermore, no studies investigated the variables that may modulate the efficacy of vaccination. The aim of this analysis was to assess whether there are modifying factors that may potentially influence the clinical efficacy of COVID-19 vaccines. A quantitative synthesis of data from Phase III trials was performed via pairwise and network meta-analyses, along with meta-regression analysis. Data from Phase III trials are currently available only for AZD1222, BNT162b2, mRNA-1237, and Sputnik V. Vaccination resulted to be generally effective (90.0%, 95%CI 72.6-96.4; p < 0.001), although the efficacy of AZD1222 (62.1%) introduced a significant level of heterogeneity in the meta-analysis (I2 92.17%, p < 0.001). No significant modifying factors resulted from the meta-regression analysis. However, considering the mRNA-based vaccines, a trend toward significance (p = 0.081) resulted for age. The network meta-analysis provided the following rank of effectiveness: BNT162b2 ≃ mRNA-1273 > Sputnik V >> AZD1222. In conclusion, no modifying factors seem to modulate the efficacy of vaccines against COVID-19. This quantitative synthesis will need to be updated as soon as further clinical results on the efficacy profile are available from Phase III trials for further licensed COVID-19 vaccines.

Identifying Early Neuropsychological Indicators of Cognitive Involvement in Multiple Sclerosis.

Multiple sclerosis (MS) is a debilitating disease of the central nervous system that is most commonly seen in early to middle adulthood, although it can be diagnosed during childhood or later in life. While cognitive impairment can become more prevalent and severe as the disease progresses, signs of cognitive involvement can be apparent in the early stages of the disease. In this review, we discuss the prevalence and types of cognitive impairment seen in early MS, including the specific measures used to identify them, as well as the challenges in characterizing their frequency and progression. In addition to examining the progression of early cognitive involvement over time, we explore the clinical factors associated with early cognitive involvement, including demographics, level of physical disability, disease modifying therapy use, vocational status, and psychological and physical symptoms. Given the prevalence and functional impact these impairments can have for persons with MS, considerations for clinicians are provided, such as the role of early cognitive screenings and the importance of comprehensive neuropsychological assessments.

The Influence of pH on Zinc Lability and Toxicity to a Tropical Freshwater Microalga.

Increased focus on the development and application of bioavailability-based metal water quality guideline values requires increased understanding of the influence of water chemistry on metal bioavailability and toxicity. Development of empirical models, such as multiple linear regression models, requires the assessment of the influence of individual water quality parameters as toxicity-modifying factors. The present study investigated the effect of pH on the lability and toxicity of zinc (Zn) to a tropical green microalga (Chlorella sp.). Zinc speciation and lability were explored using the Windermere Humic Aqueous Model (WHAM7), ultrafiltration, and diffusive gradients in thin films (DGT). Zinc toxicity increased significantly with increasing pH from 6.7 to 8.3, with 50% growth inhibition effect concentrations decreasing from 185 to 53 µg l-1 across the pH range. Linear relationships between DGT-labile Zn and dissolved Zn did not vary across the tested pH range, nor did the linear relationship between dissolved (<0.45 µm) and ultrafiltered (<3 kDa) Zn. Our findings show that Zn toxicity to this freshwater alga is altered as a function of pH across environmentally realistic pH ranges and that these toxicity changes could not be explained by Zn speciation and lability as measured by DGT and WHAM7. Environ Toxicol Chem 2021;40:2836-2845. © 2021 SETAC.

Evaluation of the Inherent Toxicity Concept in Environmental Toxicology and Risk Assessment.

Intrinsic/inherent chemical properties are characteristic, irrespective of the number of molecules present. However, toxicity is an extensive/extrinsic biochemical property that depends on the number of molecules. Paracelsus, often considered the father of toxicology, noted that all things are poisonous. Because dose magnitude (i.e., number of molecules) determines the occurrence of poisonous effects, toxicity cannot be an intrinsic/inherent biochemical property. Thus, toxicology's task is to determine case-specific risks resulting in adverse effects produced by the interaction of toxic doses/exposures, toxic mechanisms, and case-specific influencing factors. Experimental testing results are known to vary within and between chemicals, test organisms, and experimental conditions and repetitions; however, hazard-based approaches treat toxicity as a fixed and constant property. A logical alternative is the standard-risk, case-specific risk model. In this approach, testing data are defined as standard risks where the nature, magnitude, and toxicity effect is standardized to the organism, chemical, and test conditions. Interpolation/extrapolation of standard risks to site-specific conditions (i.e., case-specific risks) is challenging, requiring understanding of the influences of the complex interactions within and between differing species, conditions, and toxicity-modifying factors. Therefore, Paracelsus's paradigm is perhaps better abbreviated as "dose-causality-response", because a key interpretive requirement is establishing toxicity causality by separating mode/mechanism of toxic action from modifying factor influences in overall toxicity responses. Unfortunately, the current knowledge base is inadequate. Moving to a standard-risk-specific-risk paradigm would highlight the importance of improving the toxicity causality knowledge base. Thereby, a rationale would be provided for enhancing the design and interpretation of toxicity testing that is necessary for achieving advances in routine translation of standard-risk to specific-risk estimates-the raison d'être of regulatory risk decision making. Environ Toxicol Chem 2020;39:2351-2360. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Can the Skeletal Muscle Carnosine Response to Beta-Alanine Supplementation Be Optimized?

Carnosine is an abundant histidine-containing dipeptide in human skeletal muscle and formed by beta-alanine and L-histidine. It performs various physiological roles during exercise and has attracted strong interest in recent years with numerous investigations focused on increasing its intramuscular content to optimize its potential ergogenic benefits. Oral beta-alanine ingestion increases muscle carnosine content although large variation in response to supplementation exists and the amount of ingested beta-alanine converted into muscle carnosine appears to be low. Understanding of carnosine and beta-alanine metabolism and the factors that influence muscle carnosine synthesis with supplementation may provide insight into how beta-alanine supplementation may be optimized. Herein we discuss modifiable factors that may further enhance the increase of muscle carnosine in response to beta-alanine supplementation including, (i) dose; (ii) duration; (iii) beta-alanine formulation; (iv) dietary influences; (v) exercise; and (vi) co-supplementation with other substances. The aim of this narrative review is to outline the processes involved in muscle carnosine metabolism, discuss theoretical and mechanistic modifiable factors which may optimize the muscle carnosine response to beta-alanine supplementation and to make recommendations to guide future research.