Cause-Specific Excess Mortality During the COVID-19 Pandemic (2020-2021) in 12 Countries of the C-MOR Consortium.

BACKGROUND: This study investigated cause-specific mortality rates in 12 countries during the COVID-19 pandemic in 2020 and 2021. METHODS: We collected weekly cause-specific mortality data from respiratory disease, pneumonia, cardiovascular disease (CVD) and cancer from national vital statistic databases. We calculated excess mortality for respiratory disease (excluding COVID-19 codes), pneumonia, and CVD in 2020 and 2021 by comparing observed weekly against expected mortality based on historical data (2015-2019), accounting for seasonal trends. We used multilevel regression models to investigate the association between country-level pandemic-related variables and cause-specific mortality. RESULTS: Significant reductions in cumulative mortality from respiratory disease and pneumonia were observed in 2020 and/or 2021, except for Georgia, Northern Ireland, Kazakhstan, and Ukraine, which exhibited excess mortality for one or both causes. Australia, Austria, Cyprus, Georgia, and Northern Ireland experienced excess cumulative CVD mortality in 2020 and/or 2021. Australia, Austria, Brazil, Cyprus, Georgia, Northern Ireland, Scotland and Slovenia, experienced increased crude cumulative cancer mortality during 2020 and/or 2021 compared to previous years. Among pandemic-related variables, reported COVID-19 incidence was negatively associated with increased cancer mortality, excess respiratory, (2020) and pneumonia (2021) mortality, and positively associated with respiratory and CVD mortality (2021). Stringency of control measures were negatively associated with excess respiratory disease, CVD, and increased cancer mortality (2021). CONCLUSIONS: This study provides evidence of substantial excess mortality from CVD, and notable reductions in respiratory disease and pneumonia in both years across most countries investigated. Our study also highlights the beneficial impact of stringent control measures in mitigating excess mortality from most causes in 2021.

Hallmarks of Periodontitis.

Periodontitis is a complex polymicrobial disease of the oral cavity that affects tooth-supporting tissues. It is caused by multiple factors, such as pathogenic bacteria, genetic predisposition, and host immune response factors. The pathogenesis of periodontal disease involves the complex interrelations among bacterial toxins, several populations of cells, and host cell-secreted inflammatory mediators. Generally, periodontitis is characterized by the formation of intricate and varied biofilms of microbes on the tooth surface, commonly known as dental plaque. Activation of defense cells is characterized by releasing inflammatory mediators, such as proteases, acidic metabolites, cytokines, interleukins, and chemokines, which destroy tissue and ultimately cause bone resorption. The individual periodontal condition has a significant impact on systemic homeostasis, and its disruption can cause the development of some metabolic disorders. This review article summarizes the latest studies on the pathogenesis of periodontitis and describes the role of inflammatory mediators and genetic polymorphism in individuals, as well as relationships with some metabolic conditions. The information is collected from PubMed, Scopus, ScienceDirect, SpringerLink, and clinicaltrials.gov.

Examining a 12-year experience within Kazakhstan's national heart transplantation program.

Kazakhstan has one of the lowest heart transplantation (HTx) rates globally, but there are no studies evaluating the outcomes of HTx. This study aimed to provide a comprehensive analysis of the national HTx program over a 12-year period (2012-2023). Survival analysis of the national HTx cohort was conducted using life tables, Kaplan‒Meier curves, and Cox regression methods. Time series analysis was applied to analyze historical trends in HTx per million population (pmp) and to make future projections until 2030. The number of patients awaiting HTx in Kazakhstan was evaluated with a regional breakdown. The pmp rates of HTx ranged from 0.06 to 1.08, with no discernible increasing trend. Survival analysis revealed a rapid decrease in the first year after HTx, reaching 77.0% at 379 days, with an overall survival rate of 58.1% at the end of the follow-up period. Among the various factors analyzed, recipient blood levels of creatinine and total bilirubin before surgery, as well as the presence of infection or sepsis and the use of ECMO after surgery, were found to be significant contributors to the survival of HTx patients. There is a need for public health action to improve the HTx programme.

The Role of Vitamins, Magnesium, and Trace Elements in COVID-19 Treatment and Post-COVID-19 Rehabilitation: An Updated Overview.

This review summarizes the scientific knowledge concerning the impact of vitamins, magnesium, and trace elements on various mechanisms contributing to the possible treatment and prevention of COVID-19, including its delayed consequences. A search was conducted in various databases, including PubMed, Scopus, ClinicalTrials.- gov, and Web of Science. Among the main mechanisms involved in the effects of the studied micronutrients, immune-boosting, antioxidant and anti-inflammatory effects were also highlighted. The analyzed clinical trials confirmed that supplementation with higher daily doses of some micronutrients can reduce SARS-CoV-2 viral load and hospitalization time. The potential role of most known vitamins in preventing, treating COVID-19, and rehabilitating patients was considered. The most promising agents for combating COVID-19 and its consequences might be the following vitamins: vitamin D, ascorbic acid, polyunsaturated fatty acids (PUFAs), and some B complex vitamins. Inorganic elements deserving attention include magnesium and trace elements, such as zinc, selenium, copper, and iron. Some associations were found between micronutrient deficiencies and COVID-19 severity in children, adults, and older people. Patients can obtain the aforementioned micronutrients from natural food sources or as supplements/- drugs in various dosage forms. The reviewed micronutrients might be considered adjunctive treatment strategies for COVID-19 patients.

Perspectives on Iron Deficiency as a Cause of Human Disease in Global Public Health.

Iron (Fe) is a necessary trace element in numerous pathways of human metabolism. Therefore, Fe deficiency is capable of causing multiple health problems. Apart from the well-known microcytic anemia, lack of Fe can cause severe psychomotor disorders in children, pregnant women, and adults in general. Iron deficiency is a global health issue, mainly caused by dietary deficiency but aggravated by inflammatory conditions. The challenges related to this deficiency need to be addressed on national and international levels. This review aims to summarize briefly the disease burden caused by Fe deficiency in the context of global public health and aspires to offer some hands-on guidelines.

Evaluation of liver transplantation services in Kazakhstan from 2012 to 2023.

There is a scarcity of publications evaluating the performance of the national liver transplantation (LTx) program in Kazakhstan. Spanning from 2012 to 2023, it delves into historical trends in LTx surgeries, liver transplant centers, and the national cohort of patients awaiting LTx. Survival analysis for those awaiting LTx, using life tables and Kaplan-Meier, is complemented by time series analysis projecting developments until 2030. The overall per million population (pmp) LTx rate varied from 0.35 to 3.77, predominantly favoring living donor LTx. Liver transplant center rates ranged from 0.06 to 0.40. Of 474 LTx patients, 364 on the waiting list did not receive transplantation. The 30-day and 1-year survival rates on the waiting list were 87.0% and 68.0%, respectively. Viral hepatitis and cirrhosis prevalence steadily rose from 2015 to 2023, with projections indicating a persistent trend until 2030. Absent targeted interventions, stable pmp rates of LTx and liver transplant centers may exacerbate the backlog of unoperated patients. This study sheds light on critical aspects of the LTx landscape in Kazakhstan, emphasizing the urgency of strategic interventions to alleviate the burden on patients awaiting transplantation.

Historical evolution of healthcare systems of post-soviet Russia, Belarus, Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, Uzbekistan, Armenia, and Azerbaijan: A scoping review.

This scoping review addresses the transformation and development of new healthcare systems in nine countries -Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Russia, Tajikistan, Turkmenistan, and Uzbekistan over the period following the collapse of the Soviet Union from 1991 to the present. This assessment focuses on maternal and child health, mental health, communicable diseases, and non-communicable diseases in an effort to highlight the changes in the healthcare status of these nine countries under scrutiny. Considering that all the post-Soviet nations are officially recognized members of the World Health Organization (WHO) and have demonstrated their commitment to attaining the WHO's objectives, the evaluation of healthcare system progress and improvement was carried out utilizing indicators provided by the WHO. This review reveals that the evolution of healthcare systems could be considered sustainable, given that average life expectancy has returned to the level it was in 1991- the year of the USSR's breakup, and people's health has improved since the turn of the twenty-first century. To enhance the potential success of future healthcare reforms, however, governments must monitor implementation of the reform process, evaluate the achievement of objectives, and make necessary adjustments. The success of future healthcare changes will depend on the active involvement of the government, medical community, and patient community, as well as obtaining the support of local health authorities. This study may help identify successful and failed strategies, guiding future healthcare changes and investments.

The impact of incentive scheme on rural healthcare workforce availability: a case study of Kazakhstan.

BACKGROUND: During the 1990-2000, Kazakhstan experienced a decline in the number of healthcare professionals working in rural areas. Since 2009, the national government has been implementing financial incentives to encourage healthcare professionals to relocate to rural areas. This study aims to investigate the temporal and spatial patterns in the distribution of the rural healthcare workforce and evaluate the impact of this incentive scheme. METHODS: Interrupted Time Series Analysis using ARIMA models and Difference in Differences analyzes were conducted to examine the impact of the incentive scheme on the density of different categories of the healthcare workforce in rural Kazakhstan in the period from 2009 to 2020. RESULTS: There was a significant increase in the number of rural healthcare professionals from 2009 to 2020 in comparison to the period from 1998 to 2008. However, this increase was less pronounced in per capita terms. Moreover, a decline in the density of internists and pediatricians was observed. There is substantial variation in the density of rural nurses and physicians across different regions of Kazakhstan. The incentive scheme introduced in 2009 by the government of Kazakhstan included a one-time allowance and housing incentive. This scheme was found to have contributed insignificantly to the observed increase in the number of rural healthcare professionals. CONCLUSION: Future research should be undertaken to examine the impact made by the incentive scheme on other medical subspecialties, particularly primary practitioners. Addressing the shortage of healthcare workers in rural areas is a complex issue that requires a multifaceted approach. Aside from financial incentives, other policies could be considered to increase relocation and improve the retention of healthcare professionals in rural areas.

The Association between Parental Child Vaccination Refusal Rate and the Impact of Mass Vaccination against COVID-19 in Kazakhstan: An Interrupted Time Series Analysis with Predictive Modelling of Nationwide Data Sources from 2013 to 2022.

Despite well-established evidence supporting vaccination efficacy in reducing morbidity and mortality among infants and children, there is a global challenge with an increasing number of childhood vaccination refusals. This issue has intensified, especially during the COVID-19 pandemic. Our study aims to forecast mandatory childhood vaccination refusal trends in Kazakhstan until 2030, assessing the impact of mass COVID-19 vaccination on these rates. Utilizing annual official statistical data from 2013 to 2022 provided by the Ministry of Health of Kazakhstan, the study reveals a significant surge in refusals during the pandemic and post-pandemic periods, reaching record levels of 42,282 cases in 2021 and 44,180 cases in 2022. Notably, refusal rates sharply rose in specific regions, like Aktobe (13.9 times increase) and Atyrau (4.29 times increase), emphasizing the need for increased public healthcare attention in these areas. However, despite a decade of data, our forecasting analysis indicates a lack of volatility in childhood vaccine refusal trends for all vaccine types up to 2030, highlighting the statistical significance of the obtained results. The increasing trend in vaccine refusals underscores the necessity to enhance crisis response and support health initiatives, particularly in regions where a substantial rise in refusals has been observed in recent years.

The prevalence and risk factors of pressure ulcers among residents of long-term care institutions: a case study of Kazakhstan.

Limited information is available regarding the prevalence of pressure ulcers (PUs) in residential homes in Central Asia. Therefore, the aim of this study was to identify the prevalence rates and risk factors associated with PUs among residents of long-term care medical institutions in the Republic of Kazakhstan. This cross-sectional study was conducted in four long-term care institutions in Kazakhstan. The study sample consisted of 640 patients who were assessed for the presence of PUs and associated risk factors. The evaluation was performed using the International Prevalence Measurement of Care Quality (Landelijke Prevalentiemeting Zorgkwaliteit, LPZ), the Braden scale, and the Care Dependency Score (CDS). The overall prevalence of PUs, classified as categories I-IV, was found to be 37%. When excluding category I PUs, the prevalence decreased to 35.6%. The odds ratios (ORs) for presenting with PUs were as follows: history of stroke (OR 5.22), diseases of the digestive system (OR 10.01), presence of spinal cord lesions/paraplegia (OR 20.50), recent reported confusion within the last 7 days (OR 184.00), and limited extent dependency according to the CDS (OR 4.44; 95%CI 1.31-16.1). It is imperative to establish specialized training programs aimed at equipping medical personnel, relatives, and patients themselves with the necessary skills to provide optimal care for individuals affected by PUs.

The Role of Traditional Chinese Medicine and Chinese Pharmacopoeia in the Evaluation and Treatment of COVID-19.

The epidemic prompted by COVID-19 continues to spread, causing a great risk to the general population's safety and health. There are still no drugs capable of curing it. Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are the two other diseases caused by coronaviruses. Traditional Chinese Medicine (TCM) showed benefits in treating SARS and MERS by preventing the disease early, substantially mitigating symptoms, shortening the treatment period, and minimizing risks and adverse reactions caused by hormone therapy. Although several vaccines have been developed and are being used for the treatment of COVID-19, existing vaccines cannot provide complete protection against the virus due to the rapid evolution and mutation of the virus, as mutated viral epitopes evade the vaccine's target and decrease the efficacy of vaccines. Thus, there is a need to develop alternative options. TCM has demonstrated positive effects in the treatment of COVID-19. Previous research studies on TCM showed broad-spectrum antiviral activity, offering a range of possibilities for their potential use against COVID-19. This study shed some light on common TCM used for SARS and MERS outbreaks and their effective use for COVID-19 management. This study provides new insights into COVID-19 drug discovery.

Menopausal Status Impact on the Quality of Life in Kazakhstani Healthcare Workers: A Cross-sectional Study.

BACKGROUND: Menopausal quality of life (MenQoL) is a common concern that primary healthcare workers often encounter. Menopause has a significant impact on women's health, but studies examining its effect on the MenQoL of menopausal healthcare employees have produced conflicting results. OBJECTIVE: The aim of this study was to compare the quality of life related to menopausal status (pre-, peri-, or postmenopausal) in healthcare workers from various clinical settings in Kazakhstan. DESIGN: This was a cross-sectional study. PARTICIPANTS: In total, 222 menopausal healthcare workers (physicians, nurses/midwives, administrative staff, and cleaners) were enrolled from hospitals affiliated with the University Medical Center (UMC) in Kazakhstan. MAIN MEASURES: The outcome variable was assessed using the Menopausal Quality of Life Questionnaire (MENQOL), which evaluates MenQoL across four domains of menopausal symptoms: physical, psychological, vasomotor, and sexual. KEY RESULTS: The most frequently reported menopausal symptoms were physical ones, such as feeling tired or worn out (70.7%), followed by feeling a lack of energy (65.3%) and dry skin (64.1%). The postmenopause group had the highest mean MenQoL score in the vasomotor domain (mean 3.46 ± 1.84). There was a borderline statistical significance when comparing postmenopause and perimenopause groups in the physical domain. The pairwise comparison of mean sexual scores revealed that postmenopause women had the highest average score (3.3 ± 2.36) compared to both premenopause (mean 2.3 ± 1.82) and perimenopause (mean 2.22 ± 1.58) groups (p < 0.05). CONCLUSIONS: Menopausal status has influence on the MenQoL of healthcare workers. The study findings could have important implications for policymakers as they provide insight into the factors influencing the quality of life of menopausal healthcare employees. Creating a more menopause-friendly work environment may not only enhance the well-being of healthcare personnel but also improve their overall job satisfaction and performance.

Serum calcium and magnesium levels and quality of life in environmentally exposed populations in Kazakhstan.

The relationship between the levels of essential elements and various aspects of well-being in environmentally exposed populations still needs to be better understood. The present study aims to investigate the potential connections between serum concentrations of calcium (Ca), magnesium (Mg), and quality of life (QoL) in environmentally exposed populations in Kazakhstan. The present study involved 1881 nominally healthy individuals aged 18-52 years who were permanent residents of Abay, Borodulikha, Ust-Kamenogorsk, Kurchum, Uralsk, Aksay, and Berezovka settlements. These settlements were selected to represent different types of environmental exposure: radioactive fallout from the Semipalatinsk Nuclear Test Site (SNTS), non-ferrous metallurgy, and the condensate gas field, compared to environmentally unexposed territories. The Russian version of the SF-36 questionnaire was used to assess the participants' quality of life. Serum Ca levels were measured using colorimetry with O-cresolphthalein, and serum Mg concentrations were measured using colorimetry with xylidyl blue. Both elevated and decreased serum Ca levels were more frequently observed in the environmentally exposed populations. The prevalence of hypermagnesemia was highest among residents near the condensate gas field. Environmentally exposed populations residing near the SNTS and in Ust-Kamenogorsk exhibited lower scores in some QoL domains. In contrast, people near the condensate gas field showed comparable or even higher QoL scores than the control population. Only serum Mg demonstrated a significant association with the average QoL scores, while Ca did not show such an association. These findings have important implications for public health interventions.

Iron-related Biomarkers in the Diagnosis and Management of Iron Disorders.

BACKGROUND: Iron deficiency and iron-related disorders are common health issues worldwide, affecting a significant proportion of the population. Diagnosis and management of these disorders rely heavily on using various iron-related biomarkers that can provide valuable clinical information. OBJECTIVE: This review article provides an overview of the most commonly used iron-related biomarkers, including serum ferritin, transferrin saturation, soluble transferrin receptor, zinc protoporphyrin, and free erythrocyte protoporphyrin. Other emerging biomarkers, such as hepcidin and retinol-binding protein 4, are also discussed. RESULTS: Iron plays a vital role in various physiological processes, including oxygen transport, energy metabolism, and DNA synthesis. The article highlights the advantages and limitations of iron biomarkers and their clinical applications in diagnosing and managing iron deficiency and iron-related anemia. CONCLUSION: Using iron-related biomarkers in screening and monitoring programs can improve patient outcomes and reduce healthcare costs.

Genetic and Epigenetic Determinants of COVID-19 Susceptibility: A Systematic Review.

BACKGROUND: The molecular mechanisms regulating coronavirus pathogenesis are complex, including virus-host interactions associated with replication and innate immune control. However, some genetic and epigenetic conditions associated with comorbidities increase the risk of hospitalization and can prove fatal in infected patients. This systematic review will provide insight into host genetic and epigenetic factors that interfere with COVID-19 expression in light of available evidence. METHODS: This study conducted a systematic review to examine the genetic and epigenetic susceptibility to COVID-19 using a comprehensive approach. Through systematic searches and applying relevant keywords across prominent online databases, including Scopus, PubMed, Web of Science, and Science Direct, we compiled all pertinent papers and reports published in English between December 2019 and June 2023. RESULTS: The findings reveal that the host's HLA genotype plays a substantial role in determining how viral protein antigens are showcased and the subsequent immune system reaction to these antigens. Within females, genes responsible for immune system regulation are found on the X chromosome, resulting in reduced viral load and inflammation levels when contrasted with males. Possessing blood group A may contribute to an increased susceptibility to contracting COVID-19 as well as a heightened risk of mortality associated with the disease. The capacity of SARS-CoV-2 involves inhibiting the antiviral interferon (IFN) reactions, resulting in uncontrolled viral multiplication. CONCLUSION: There is a notable absence of research into the gender-related predisposition to infection, necessitating a thorough examination. According to the available literature, a significant portion of individuals affected by the ailment or displaying severe ramifications already had suppressed immune systems, categorizing them as a group with elevated risk.

Sleep, Dietary Melatonin Supplementation, and COVID-19.

BACKGROUND: During the COVID-19 pandemic, people suffered from major mental health problems. These include stress, anxiety, and confusion about the existing situation of home confinement. Melatonin is a popular anti-inflammatory and antioxidant molecule sold as an over-the-counter dietary supplement. OBJECTIVE: This review discusses the indications for using melatonin in the context of the COVID-19 pandemic, including treatment. METHODS: A comprehensive search of publications was conducted in electronic databases focusing on the administration of melatonin in COVID-19. RESULTS: Stress has a huge negative impact on sleep routines and the quality of life of individuals. Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The administration of melatonin protects against viral and other pathogens and speeds clinical recovery. CONCLUSION: In patients admitted to intensive care units, melatonin decreases the risks of severe complications, such as thrombosis and sepsis, and mortality rates. In addition, it is efficacious in lowering vessel permeability, depression, and sedation, and improving the quality of sleep, which could also help COVID-19 patients achieve better clinical outcomes.

Characteristics of the Online Market for Anabolic-Androgenic Steroids in Central Asia: A Netnographic Analysis.

Background: With the online proliferation of illegal substances, the Internet offers a wide variety of information on the acquisition and intake of anabolic-androgenic steroids (AAS) and other performance and image enhancing drugs. This study focuses on investigating the characteristics of the online AAS market in Central Asia. OBJECTIVES: The primary objectives of this study were to investigate the accessibility and features of the online market for AAS in Central Asia. To achieve this, we employed a netnographic approach for a systematic exploration of websites advertising and selling AAS. The study aimed to conduct a comprehensive analysis of several key aspects, including the variety of AAS products offered, the quality of health advice provided the level of product availability, the procedures involved in making purchases, and the pricing structures within this market. RESULTS: Twenty-one websites supplying AAS in Central Asia met our inclusion criteria. Using content analysis, data were gathered on AAS offerings, quality of health advice provided, availability, purchase process, and prices. Data were synthesized using descriptive statistics. Results indicate that AAS are easily accessible for purchase without valid medical prescription in the Central Asia online market. Most websites advertised the aesthetic and ergogenic benefits of AAS use without indicating the potential complications and adverse effects. CONCLUSIONS: Public health efforts to mitigate AAS use in Central Asia should consider both the online accessibility of AAS and the lack of accompanying information on potential complications as well as adverse effects associated with their use. Efforts must be intensified to curtail the proliferation of AAS and related misleading information on the Central Asian online market.

Cervical Cancer Prevention in Rural Areas.

Objective: Globally, cervical cancer (CC) incidence is higher in rural areas than in urban areas that could be explained by the influence of many factors, including inequity in accessibility of the CC prevention measures. This review aimed to identify and analyze factors associated with a lack of cervical cancer screening and HPV vaccination programs in people living in rural areas and to outline strategies to mitigate these factors. Methods: The literature search encompassed two focal domains: cervical cancer screening and HPV vaccination among populations residing in rural areas, covering publications between January 1, 2004 to December 31, 2021 in the PubMed, Google Scholar, Scopus, and Cyberleninka databases, available in both English and Russian languages. Result: A literature review identified 22 sources on cervical cancer screening and HPV vaccination in rural and remote areas. These sources revealed similar obstacles to screening and vaccination in both high and low-income countries, such as low awareness and knowledge about CC, screening, and HPV vaccination among rural residents; limited accessibility due to remoteness and dearth of medical facilities and practitioners, associated with a decrease in recommendations from them, and financial constraints, necessitating out-of-pocket expenses. The reviewed sources analyzed strategies to mitigate the outlined challenges. Possible solutions include the introduction of tailored screening and vaccination campaigns designed for residents of rural and remote locations. New screening and vaccination sites have been proposed to overcome geographic barriers. Integrating HPV testing-based CC screening is suggested to counter the lack of healthcare personnel. HPV vaccination is essential for primary cervical cancer prevention, especially in rural and remote areas, as it requires less medical infrastructure. Conclusion: Certain measures can be proposed to improve the uptake of CC screening and HPV vaccination programs among rural residents, which are needed to address the higher prevalence of CC in rural areas. Further investigation into cervical cancer prevention in rural and remote contexts is necessary to ascertain the optimal strategies that promote health equity.

Porphyrinuria in Autism Spectrum Disorder: A Review.

Numerous studies demonstrated that the number of children with autism spectrum disorder (ASD) has increased remarkably in the past decade. A portion of ASD etiology, however, is attributed to environmental issues and genetic disorders. We highlighted a scoping review to principally evaluate the current information on mercury exposure in ASD children and to reveal knowledge gaps. Elevated porphyrins concentration in the urinary system related to mercury exposure, such as precoproporphyrin (prcP), coproporphyrin (cP), and pentacarboxyporphyrin (5cxP), was shown in comparison with controls. Moreover, high levels of urinary porphyrins have been elevated in response to heavy metal exposure. The related pattern (increased prcP, cP, and 5cxP) with Hg exposure may be used as biomarkers in the characteristics of ASD symptoms. However, this review highlighted the data gaps because the control groups were not genderand age-matched for ASD children.

Abnormal Porphyrin Metabolism in Autism Spectrum Disorder and Therapeutic Implications.

Autism spectrum disorder (ASD) is a mosaic of neurodevelopmental conditions composed of early-onset social interaction and communication deficits, along with repetitive and/or restricted patterns of activities, behavior, and interests. ASD affects around 1% of children worldwide, with a male predominance. Energy, porphyrin, and neurotransmitter homeostasis are the key metabolic pathways affected by heavy metal exposure, potentially implicated in the pathogenesis of ASD. Exposure to heavy metals can lead to an altered porphyrin metabolism due to enzyme inhibition by heavy metals. Heavy metal exposure, inborn genetic susceptibility, and abnormal thiol and selenol metabolism may play a significant role in the urinary porphyrin profile anomalies observed in ASD. Altered porphyrin metabolism in ASD may also be associated with, vitamin B6 deficiency, hyperoxalemia, hyperhomocysteinemia, and hypomagnesemia. The present review considers the abnormal porphyrin metabolism in ASD in relation to the potential pathogenic mechanism and discusses the possible metabolic therapies such as vitamins, minerals, cofactors, and antioxidants that need to be explored in future research. Such targeted therapeutic therapies would bring about favorable outcomes such as improvements in core and co-occurring symptoms.