Over five percent of children and adolescents are diagnosed with attention deficit/hyperactivity disorder (ADHD) globally. This condition is characterized by a short attention span, hyperactivity or impulsive behavior that is age-inappropriate, making it difficult for patients to navigate interpersonal relationships, the formal education system, and social life. Researchers have used brain imaging analyses such as magnetic resonance imaging (MRI) to understand the neurological basis of ADHD. Understanding brain structure abnormalities that lead to ADHD-related pathologies is crucial for designing early assessment and intervention systems, especially for children.
Although multiple studies have used MRI to understand ADHD in children, the results have been inconclusive. While some brain imaging studies have shown decreased gray matter volume (GMV) in children with ADHD, others have either reported no change or an increase in GMV compared to subjects without ADHD. These conflicting results are mostly due to small sample sizes, differences in MRI machines used, or the variation among the subjects recruited. Previous studies have accounted for the bias caused by different MRI machines using a method called ComBat harmonization, which controls for site and MRI differences in large samples. However, ComBat overcorrects sampling bias, which may include biological characteristics of the sample; therefore, it may not be able to accurately correct the MRI differences.
The traveling-subject (TS) method is a new correction approach to account for variations in measurements across MRI machines for the same subject. In this method, measurement biases can be controlled for the same participants using MRI scans from multiple institutions, facilitating the collection of more accurate datasets. In this collaborative study, Assistant Professor Qiulu Shou and Associate Professor Yoshifumi Mizuno from the University of Fukui, Japan, Professor Yoshiyuki Hirano from Chiba University, Japan, and Professor Kuriko Kagitani-Shimono at The University of Osaka, Japan, validated the TS method in an independent dataset. Their findings were published in Molecular Psychiatry on August 8, 2025.
Dr. Shou introduces the methodological framework of the study: “MRI data of 14 TS, 178 typically developing (TD) children, and 116 children with ADHD were collected from multiple sites, and the TS method and ComBat were used to correct for measurement bias.” Fourteen healthy subjects underwent MRI scans on four different machines over a three-month period to extract measurement biases across these machines. This was then applied to an independent dataset of children from the Child Developmental MRI (CDM) database. The CDM database was jointly established by the University of Fukui, The University of Osaka, and Chiba University, with the goal of collecting brain imaging data from over 1,000 child participants for research on neurodevelopmental disorders such as ADHD. GMV was then estimated and compared between the two groups of children in the study. The research team calculated measurement and sampling biases among TS-corrected, ComBat-corrected, and raw data. The results showed that compared to raw data, the TS method significantly reduced measurement bias while maintaining sampling bias. In contrast, ComBat effectively reduced measurement bias and significantly decreased sampling bias.
“TS-corrected data showed decreased brain volumes in the frontotemporal regions in the ADHD group compared to the TD group,” explains Dr. Mizuno while discussing their findings. “Patients with ADHD displayed smaller volumes in those regions of the brain that are crucial for cognitive functions, such as information processing and emotional control, which are often affected in these patients,” adds Dr. Shou.
Furthermore, if TS-harmonized multi-site MRI data on specific brain structure patterns can be associated with ADHD, they can then be used as neuroimaging biomarkers for accurate and early ADHD diagnosis, treatment, and treatment outcome monitoring, leading to effective personalized therapeutic strategies.
“By applying the TS harmonization method to correct for site-related biases in multi-site MRI data, this study aims to identify brain structure characteristics in children with ADHD. These identified characteristics could facilitate earlier diagnosis and more precise, individualized interventions. In the long term, this approach may improve the quality of life for affected children and reduce the risk of secondary psychiatric disorders,” concludes Dr. Shou.
Source:
Journal reference:
Shou, Q., et al. (2025). Brain structure characteristics in children with attention-deficit/hyperactivity disorder elucidated using traveling-subject harmonization. Molecular Psychiatry. doi.org/10.1038/s41380-025-03142-6
Hypertension (HTN), a major modifiable risk factor for all-cause morbidity and mortality worldwide, is strongly associated with functional or organic damage to vital organs (heart, brain, and kidneys) and an elevated risk of cardiovascular diseases (CVD).1,2 Consequently, effective prevention of HTN is paramount to reducing the global disease burden and extending human lifespan.3
Fatty liver disease (FLD) has emerged as a significant public health concern in recent years, primarily due to the escalating prevalence of diabetes and obesity. FLD is closely associated with a spectrum of metabolic disorders, including but not limited to centripetal obesity, dyslipidemia, hyperglycemia, and hepatic dysfunction.4
A landmark meta-analysis encompassing 11 observational cohort studies (n=390,348 hypertension-free adults across diverse populations) revealed that FLD confers a 66% increased risk of incident HTN (HR=1.66, 95% CI: 1.38–2.01) over a median 5.7-year follow-up.5 Emerging evidence further establishes FLD not only as a pivotal risk factor and accelerator of HTN progression but also as a mediator in obesity-related hypertensive pathogenesis.6 Given the adverse prognostic implications of HTN and FLD comorbidity, proactive screening for HTN in FLD patients is clinically imperative to predict CVD morbidity and mortality in this population.
Insulin resistance (IR) constitutes a central pathophysiological mechanism in FLD development,7 driving excessive production of lipotoxic and proinflammatory mediators that induce hepatic steatosis and injury.8 This IR-driven cascade may represent the principal link between FLD and hypertension. However, conventional IR biomarkers such as the homeostasis model assessment of insulin resistance (HOMA-IR)9 are often influenced by the accuracy of insulin measurements and exhibit poor reproducibility.10,11 Therefore, a non-insulin numerical index, such as the triglyceride-glucose-body mass index (TyG-BMI), may serve as a more convenient, practical, and cost-effective alternative for assessing IR.
Recent investigations have highlighted the TyG-BMI index as a promising alternative. Liu et al reported a robust independent association between TyG-BMI and HTN susceptibility, with findings remaining consistent after comprehensive covariate adjustment.12 Substantiating this, an Iranian population-based study demonstrated that elevated TyG-BMI levels correlated with increased HTN odds, outperforming both BMI and TyG index alone in discriminating hypertensive status.13
Nevertheless, critical knowledge gaps persist regarding the TyG-BMI-hypertension relationship specifically in FLD populations and the diagnostic accuracy of TyG-BMI for HTN prediction in this context. To address these pivotal questions, this study aims to investigate the association between TyG-BMI and HTN incidence and to evaluate the diagnostic utility of TyG-BMI for HTN detection in FLD patients.
This cross-sectional study initially enrolled 10186 patients with ultrasound-confirmed FLD from the Health Examination Center of Chengde Medical University Affiliated Hospital between September 2023 and September 2024. After excluding participants with incomplete data on key variables (eg, blood pressure, TyG-BMI components), 6,257 eligible individuals were stratified into two groups: 2,804 cases in the HTN group (FLD-HTN) and 3,453 controls in the normotensive group (FLD-0). The study protocol was approved by the Institutional Ethics Committee of Chengde Medical University Affiliated Hospital (No. CYFYLL2020147) in accordance with the Declaration of Helsinki. The requirement for informed consent was waived due to the retrospective nature of data collection.
Height, weight, and BP were measured by a trained internist using standardized equipment. BMI was calculated as weight in kilograms divided by height in meters squared (kg/m²). After the participant had rested for at least 15 minutes in a seated position, BP was measured three times on the non-dominant arm using an automated sphygmomanometer (OMRON HEM-7312), with at least 1-minute intervals between measurements. The mean of the three readings was recorded for analysis.
All participants fasted for 10 hours prior to venipuncture. Five milliliters of venous blood were collected from an antecubital vein. Serum samples were separated by centrifugation and analyzed on a Beckman AU5800 automated analyzer. Biochemical parameters, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total cholesterol (TC), triglycerides (TG), fasting blood glucose (FBG), and total protein (TP), were measured spectrophotometrically. Blood urea nitrogen (BUN) was measured enzymatically, while serum creatinine (Scr) and uric acid (UA) were determined via ion-selective electrode methodology.
The TyG index was calculated using the following equation:
.16
TyG-BMI was calculated using the following equation:
.17
Data were analyzed using SPSS 26.0 and R 4.2.1 with two-tailed α=0.05. Continuous variables with normal distribution are presented as mean ± SD, while skewed variables as median (Q1-Q3). Categorical variables were expressed as n (%) and compared using chi-square tests.
Group comparisons:Applied Kruskal–Wallis H-tests (non-parametric) or one-way ANOVA (parametric) with post-hoc Bonferroni corrections for multiple comparisons across TyG-BMI quartiles. Regression analyses: Conducted stepwise multivariate linear regression after verifying absence of multicollinearity.Performed univariate logistic regression to identify HTN-associated factors.Developed adjusted multivariate logistic models incorporating covariates: age, sex, ALT, AST, TC, etc. Diagnostic performance: Evaluated TyG-BMI’s predictive capacity using receiver operating characteristic (ROC) curves, with area under the curve (AUC) comparisons via DeLong’s test.
The study cohort comprised 6,257 FLD patients, including 2,804 hypertensive (FLD-HTN) and 3,453 normotensive (FLD-0) individuals. As detailed in Table 1, FLD-HTN participants exhibited significantly higher age prevalence (P < 0.001), male predominance (P < 0.001), and elevated BMI (P < 0.001) compared to FLD-0 controls. Metabolically, the FLD-HTN group demonstrated marked elevations in glycemic parameters (FBG, TyG index, TyG-BMI), lipid profiles (TC, TG, LDL-C, HDL-C), hepatic enzymes (ALT, AST, GGT), and renal biomarkers (SCr, BUN, UA) (all P < 0.01).
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Table 1 Clinical and Biochemical Characteristics of the Study Population
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Scatterplot analysis (Figure 1) revealed progressive increases in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) with rising TyG-BMI values. Spearman correlation analysis confirmed positive associations between TyG-BMI and SBP (r=0.264, P < 0.001) as well as DBP (r=0.263, P < 0.001).
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Figure 1 Scatter Plots Illustrating the Association between TyG-BMI Index and SBP and DBP Status. (A) SBP, (B) DBP. Each point represents an individual patient. The correlations between SBP and DBP with the TyG-BMI index were evaluated using the Spearman correlation test. A P value < 0.05 indicates a statistically significant difference.
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Univariate logistic regression (Table 2) identified male sex, advanced age, elevated BMI, and dysregulated glucolipid metabolism as significant HTN risk predictors (all P<0.05). Multivariate models (Table 3) maintained these associations: Model I (adjusted for age/sex): TyG-BMI retained significant predictive value (OR=1.24, 95% CI:1.18–1.31).
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Table 2 Univariate Logistic Regression Analysis for HTN
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Table 3 Multifactor Logistic Regression Analysis for HTN
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Model II (full metabolic adjustment): TyG-BMI remained independently associated with HTN risk (OR=1.17, 95% CI:1.10–1.25).
ROC analysis (Table 4 and Figure 2) demonstrated superior discriminative capacity of TyG-BMI (AUC=0.624, 95% CI:0.610–0.638) compared to TyG (AUC=0.603) and BMI (AUC=0.593) (P < 0.01 by DeLong’s test). Notably, TyG and BMI showed comparable predictive utility (P=0.321 for AUC difference).
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Table 4 Areas Under the Receiver Operating Characteristic Curves for Each Evaluated Parameters in Identifying Hypertension
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Figure 2 ROC Curves of TyG, BMI, and TyG-BMI Indexes for Predicting FLD-HTN. This figure displays the ROC curves for the TyG, BMI, and TyG-BMI indices in predicting FLD-HTN. The comparison of the areas under the curve (AUC) was performed, and a P value < 0.05 indicates a statistically significant difference in AUC.
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Quartile stratification of TyG-BMI (Q1: ≤217.90, n=1,565; Q2:217.90–239.28, n=1,564; Q3:239.28–264.29, n=1,564; Q4:>264.29, n=1,564) revealed dose-dependent metabolic deterioration (Table 5). Q4 exhibited peak values in FBG, TC, TG, LDL-C, hepatic enzymes, and UA (all P < 0.001), alongside minimal HDL-C levels (P < 0.001).
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Table 5 Demographic and Clinical Characteristics of Participants by TyG-BMI Index
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Stratified analysis (Figure 3A and B) showed stepwise increases in both SBP and DBP across ascending TyG-BMI quartiles (P < 0.001). HTN prevalence escalated from 32.7% in Q1 to 58.1% in Q4 (P < 0.001) (Figure 3C). Multivariable-adjusted logistic regression (Table 6) confirmed gradient HTN risks: Q4 demonstrated 3.21-fold higher odds (95% CI:2.78–3.71) versus Q1 after full adjustment.
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Table 6 Multivariate Logistic Regression Analysis of HTN Risk Across TyG-BMI Quartiles
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Figure 3 Blood Pressure Distribution According to TyG-BMI Index Quartiles. (A) Mean and standard error of SBP, (B) Mean and standard error of DBP, (C) Percentage distribution of blood pressure categories.****P < 0.0001.
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FLD has emerged as the most prevalent chronic liver disorder worldwide in recent decades, affecting approximately 25% of the adult population. Previous studies have demonstrated that both the presence and severity of FLD are associated with elevated BP, prehypertension, and established HTN.18,19 This study is the first to investigate the association between the TyG-BMI index and HTN specifically in FLD patients, while validating its clinical utility as a predictive biomarker in this population. Our results demonstrate that TyG-BMI not only serves as an independent risk factor for incident HTN in FLD patients (OR=3.362, 95% CI: 2.827–3.999), but also exhibits superior predictive performance (AUC=0.624) compared to conventional indices including BMI (AUC=0.593) and the TyG index (AUC=0.603). By focusing specifically on patients with FLD, these findings highlight the potential utility of the TyG-BMI index in this specific population and offer valuable insights for early intervention strategies targeting this metabolic disorder. Huang et al20 demonstrated a significant association between TyG-BMI and HTN risk (OR=1.31, 95% CI: 1.25–1.37) in 2,016 Japanese non-diabetic participants comparing normotensive and HTN individuals. Similarly, Peng et al21 established significant positive correlations of TyG-BMI with both high-normal blood pressure and HTN among 15,464 non-diabetic subjects. Notably, TyG-BMI exhibited superior predictive value over BMI and TyG index in identifying these conditions, consistent with our observations.
The HTN in individuals with FLD demonstrates distinct pathophysiological features. While adverse lifestyle factors and metabolic dysregulation influence HTN risk in both FLD and non-FLD populations, FLD itself acts as a pivotal intermediary linking lifestyle behaviors, metabolic disturbances, and HTN development.22 Existing evidence indicates that IR constitutes a key mechanistic link between FLD and HTN.23 Notably, IR, closely associated with metabolic syndrome, is a well-established independent risk factor for HTN. Firstly, compensatory hyperinsulinemia induced by IR may stimulate carotid body chemoreceptors, augmenting sympathetic nervous system activity. This cascade elevates epinephrine and norepinephrine secretion, consequently increasing cardiac output and peripheral vascular resistance.24,25 Secondly, IR activates the renin-angiotensin-aldosterone system (RAAS), promoting angiotensin II generation. This leads to small artery vasospasm, elevated glomerular hydrostatic pressure, and stimulated aldosterone synthesis with enhanced renal sodium reabsorption, ultimately expanding circulatory volume and elevating BP.26 Furthermore, under IR conditions, oxidative stress and mitochondrial dysfunction may reduce bioavailable nitric oxide while increasing endothelin production, thereby exacerbating vasoconstriction.27–29 In populations with FLD, IR, dyslipidemia, and chronic inflammation are generally more prevalent and severe, thereby strengthening their association with HTN.30 Furthermore, hepatic steatosis and inflammation may directly promote dysregulated BP control via multiple mechanisms, including altered adipokine profiles (eg, leptin and adiponectin), proinflammatory cytokine release, oxidative stress, sympathetic nervous system hyperactivity, and renin-angiotensin-aldosterone system (RAAS) activation.31 Although these mechanisms also contribute to HTN pathogenesis in individuals without FLD, HTN in this group primarily arises from vascular structural/functional alterations, salt sensitivity, genetic factors, and RAAS activity, rather than direct hepatic lipid accumulation and inflammatory processes.
Crucially, we further identified a significant positive association between TyG-BMI and HTN risk in FLD patients, showing a graded increase in risk with increasing index values. As an integrated biomarker reflecting IR, dysglycemia, dyslipidemia, and obesity, TyG-BMI offers mechanistic insights into the pathogenesis of HTN in FLD. These findings provide critical evidence for the early identification of high-risk patients and the design of targeted interventions. Future studies should elucidate its precise pathophysiological pathways to optimize strategies for HTN prevention. Notably, our subgroup analysis revealed an inverse relationship between TyG-BMI and age. This phenomenon may be attributed to younger individuals adopting unhealthy lifestyles—including sedentary behaviors and nutritional imbalances—during rapid societal development, consequently accelerating metabolic dysfunction. This observation aligns with the global trend toward earlier-onset metabolic disorders, highlighting the necessity for intensified BP monitoring in young and middle-aged FLD populations.
Although this study is the first to investigate the relationship between TyG-BMI and HTN in FLD patients, several limitations must be acknowledged. First, all data were derived from health examinations of residents in Chengde city, and the age/sex distribution of our cohort may not reflect that of the general population, thus limiting the generalizability of our findings. Second, while statistical analyses can identify associations, they cannot directly elucidate the comprehensive molecular-level disease mechanisms. A complete understanding requires integrating statistical findings with fundamental investigations, such as cellular experiments, animal models, and molecular biology techniques, for multi-level validation. Furthermore, due to covariate limitations within our dataset, we acknowledge the absence of critical variables, including dietary patterns and alcohol consumption data. In summary, while this study provides preliminary evidence supporting the association between TyG-BMI and HTN risk in patients with FLD, future research should incorporate multicenter cohort studies and mechanistic investigations to overcome the aforementioned limitations, thereby advancing a more comprehensive understanding of this association.
This study establishes TyG-BMI as a robust predictor of HTNrisk in FLD patients, exhibiting associations with HTN severity and superior diagnostic performance to traditional indices. These findings provide a risk-stratification framework to guide targeted prevention strategies, particularly for young FLD populations experiencing accelerated metabolic dysregulation.
Original data can be obtained via Email to the corresponding author upon reasonable request.
This study was approved by the Ethics Committee of the Affiliated Hospital of Chengde Medical University (No. CYFYLL2020147) and the requirement for informed consent was waived due to the retrospective nature of the study. This study was performed in adherence to the principles of the Declaration of Helsinki. All data collected was anonymised in accordance with the Personal Information Protection Law of the People’s Republic of China. All patient data used is nonidentifiable and confidential.
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
This study was supported by the Natural Science Foundation of the Hebei Province (Project No. C2022406011) and the Construction of the Chengde Biomedical Industry Research Institute (202205B086).
The authors declare no conflicts of interest in this work.
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Most people with high blood pressure aren’t skipping the salt shaker in favor of a salt substitute, according to a new study.
Incredibly few Americans use salt substitutes, essentially waving aside a simple and effective way to manage their blood pressure, researchers reported Thursday at an American Heart Association meeting in Baltimore.
“Overall, less than 6% of all U.S. adults use salt substitutes, even though they are inexpensive and can be an effective strategy to help people control blood pressure, especially people with difficult-to-treat high blood pressure,” lead researcher Yinying Wei said in a news release. She is a doctoral candidate in applied clinical research and hypertension at UT Southwestern Medical Center in Dallas.
Salt substitutes replace some or all of the sodium with potassium, which tastes similar to regular salt, researchers said in background notes.
A salt-heavy diet causes the body to retain fluid, which can increase blood pressure by drawing more water into the bloodstream, according to the Cleveland Clinic.
For the new study, researchers analyzed data from the National Health and Nutrition Examination Survey gathered between 2003 and 2020, using food questionnaires to track use of salt substitutes.
Overall, salt substitute use among U.S. adults remained low during the study period. At most, more than 5% used salt substitutes during the 2013-2014 survey.
These results were similar when looking at adults who would benefit from salt substitutes. Only a little more than 5% used them overall, researchers found.
Use was most common in people with high blood pressure who were taking medications for the condition, with nearly 11% turning to salt substitutes.
Next most common were people with drug-resistant high blood pressure, with more than 7% using salt substitutes.
However, salt substitute use remained consistently less than 6% among people with untreated high blood pressure, researchers found.
“Salt substitute use remained uncommon over the last two decades including among people with high blood pressure,” Wei said. “Even among individuals with treated and poorly managed or untreated high blood pressure, most continued to use regular salt.”
These results highlight “an important and easy missed opportunity to improve blood pressure in the U.S. — the use of salt substitutes,” Dr. Amit Khera said in a news release. Khera is clinical chief of cardiology and director of preventive cardiology at UT Southwestern Medical Center in Dallas.
“The fact that use of salt substitutes remains so low and has not improved in two decades is eye-opening and reminds patients and health care professionals to discuss the use of these substitutes, particularly in visits focused on high blood pressure,” added Khera, who was not involved in the study.
The AHA recommends consuming no more than 2,300 milligrams of sodium daily, with an ideal limit of less than 1,500 mg per day for most adults.
For most people, cutting sodium back by 1,000 mg a day can improve their blood pressure and heart health, researchers said.
Findings presented at medical meetings should be considered preliminary until published in a peer-reviewed journal.
More information
The Cleveland Clinic has more on the potential harms from excess salt.
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A drug already prescribed for type 2 diabetes and obesity may one day be used to treat cocaine addiction. In animal studies, researchers at the University of Gothenburg, Sweden, found that semaglutide reduced both cocaine use and relapse.
One of the world’s most prescribed drugs for type 2 diabetes and obesity, semaglutide also reduced rats’ motivation to keep taking cocaine. Scientists believe the drug may blunt cocaine’s ability to raise dopamine levels in the brain, lowering the sense of reward. Exactly how semaglutide works in the brain is still not fully understood.
The study, published in the journal European Neuropsychopharmacology, was based on experiments in which rats were trained to self-administer cocaine. On average, cocaine use dropped by 26 percent, relapse-like behavior by 62 percent, and motivation to seek the drug by 52 percent.
The lead author is Cajsa Aranäs, a researcher at the Sahlgrenska Academy, University of Gothenburg:
“Our results show that an established drug can affect key behaviors behind cocaine addiction. We hope this could open the way for new treatments, but clinical trials are needed before we know if the same effect is seen in patients.”
Elisabet Jerlhag, Professor of Pharmacology at the Sahlgrenska Academy, University of Gothenburg, led the study:
“There is a pressing demand for treatments for cocaine addiction. Currently, no drugs are available, and the risk of relapse is very high. If these findings in rats hold up in clinical trials, semaglutide could become the first pharmacological option to complement psychological therapy and support programs.”
Several GLP-1 receptor drugs are currently approved worldwide, but semaglutide is the best known, sold under names such as Ozempic and Wegovy.
Source:
Journal reference:
Aranäs, C., et al. (2025). Semaglutide suppresses cocaine taking, seeking, and cocaine-evoked dopamine levels in the nucleus accumbens. European Neuropsychopharmacology. doi.org/10.1016/j.euroneuro.2025.07.001
Pancreatic islets (artificially coloured) no longer secrete sufficient insulin in people with type 1 diabetes. Credit: Steve Gschmeissner/Science Photo Library
In a medical first, researchers report that they have implanted CRISPR-edited pancreas cells into a person with type 1 diabetes. The cells pumped out sugar-regulating insulin for months — without the need for the recipient to take immune-dampening drugs, thanks to gene edits that allowed the cells, collected from a deceased donor, to evade detection by the recipient’s immune system1.
The study, orchestrated by the firm Sana Biotechnology in Seattle, Washington, raises hopes of an enduring cure for an autoimmune disease that consigns millions of people to a life of strict monitoring and dependence on injected insulin. “The preliminary data has definitely lifted the spirits of our community — and it’s a really elegant approach”, says Aaron Kowalski, the chief executive of Breakthrough T1D, a non-profit organization in New York City formerly known as JDRF.
Stealthy stem cells to treat disease
The ultimate goal is to apply immune-cloaking gene edits to stem cells and then direct their development into insulin-secreting islet cells. Unedited islets made from stem cells have already shown promise for treating type 1 diabetes in a small trial, according to results published in June2.
But some independent research groups have failed to confirm that the Sana method confers immune-skirting abilities on edited cells. And the study involved only one person who received a low dose of cells for a short time — not enough “to achieve insulin independence, so clinical efficacy remains unproven”, says Tim Kieffer, a molecular endocrinologist at the University of British Columbia in Vancouver, Canada.
Still, Kieffer calls the demonstration of immune cloaking “convincing” and “a major milestone toward the goal of effective cell therapy without chronic immunosuppression”. Kieffer previously held the role of chief scientific officer at biotechnology company ViaCyte (that has since been acquired by Vertex Pharmaceuticals in Boston, Massachusetts), which, like Sana, focused on developing cell therapies for type 1 diabetes.
Currently, the only way for someone with type type 1 diabetes to avoid dependence on injected insulin is through the transplantation of cadaveric islet cells. The procedure can restore insulin production for years, but it is rarely performed — constrained by the scarcity of donor pancreases and the need for lifelong immune-suppressing drug therapy, which carries risks of infection, cancer and other serious side effects.
‘Smart’ insulin prevents diabetic highs — and deadly lows
To address the donor shortage, some companies have turned to stem-cell technologies to generate limitless supplies of replacement islets in the laboratory.
Vertex is furthest along. As reported in June, the company transplanted embryonic stem-cell-derived islets into 12 people with type 1 diabetes. After one year, ten participants no longer required insulin injections2. The company plans to seek regulatory approval for this cell therapy next year.
In a similar vein, scientists at regenerative-medicine company Reprogenix Bioscience in Hangzhou, China, are creating islets from reprogrammed stem cells derived from a recipient’s own fat tissue, with early reports of success3. Both approaches, however, still require recipients to take anti-rejection drugs, either to fend off immune attacks on donor cells or to counter the autoimmune assault that persists even against a person’s own cells.
Sana’s strategy aims to bypass the need for those drugs entirely. Company scientists began with islets from a deceased donor who did not have diabetes. Using CRISPR gene editing system, the researchers disabled two genes that normally help to flag foreign invaders to T cells, the immune system’s front-line defender. They then used a virus to shuttle genetic instructions for a protein called CD47 into the cells. This protein serves as a protective ‘do not eat me’ signal that prevents immune watchdogs, known as natural killer cells, from attacking the edited cells.
Brain cells given an ‘invisibility cloak’ fix Parkinson’s symptoms in rats
Arina Nursafrina Rahmatina,1,* Mohammad Ghozali,2,* Qorinah Estiningtyas Sakilah Adnani,3 Dany Hilmanto,4 Yenni Zuhairini,3 Hadi Susiarno,5 Ramdan Panigoro2
1Master of Midwifery Program, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 2Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, West Java, Indonesia; 3Department of Public Health, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 4Department of Pediatrics, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 5Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Padjadjaran/Dr, Hasan Sadikin General Hospital, Bandung, West Java, Indonesia
Correspondence: Mohammad Ghozali, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Jalan Raya Bandung-Sumedang Km. 21, Jatinangor, West Java, 45363, Indonesia, Tel +6281320359090, Fax +62227795595, Email [email protected]
Abstract: Anemia is a significant health concern in adolescents, linked to diminished physical stamina and productivity. Menstruation is a prevalent cause of iron deficiency anemia. If this persists until pregnancy, it may elevate the risk of having infants with low birth weight. Consequently, efficacious preventive interventions are necessary. This literature review investigates the correlation between dietary intake and physical activity with anemia in adolescent girls. The evaluation was per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. A thorough search was conducted across various databases, including PubMed (n = 59), Scopus (n = 103), and ScienceDirect (n = 5546), along with manual citation tracking (n = 6) and previously published reviews (n = 2), yielding a total of 5708 articles. Following the screening process, 157 articles were eliminated for irrelevance, four articles were deemed inaccessible, and 14 articles were added based on the eligibility assessment. The results emphasize that macronutrient and micronutrient consumption are essential for erythropoiesis and the prevention of anemia. Dietary diversity and sufficient energy intake were substantially correlated with enhanced anemia status. Furthermore, moderate to strenuous physical activity correlated favorably with hemoglobin and ferritin concentrations. Excessive body fat may impede iron absorption. Overall, sufficient dietary consumption and consistent physical exercise seem complementary to preventing anemia. This is important as an effort to prevent disease throughout the life span because anemia that persists into adulthood hurts pregnancy, childbirth, and the health outcomes of the newborn. However, we have not identified a certain frequency and duration of activity that affects anemia. Consequently, additional investigation is required regarding this matter.
Keywords: nutritional intake, physical activity, iron deficiency, female adolescents, anemia
Anemia constitutes a significant global health issue. Globally, there are 1.9 billion instances of anemia, with 30% occurring in women aged 15 to 49.1–3 Menstruation in women is a prevalent cause of iron deficiency anemia.4 Mitigating anemia is a global health goal; nevertheless, not all nations have succeeded in attaining a 50% reduction in its prevalence.5 Anemia can result in a decrease in body resistance and cognitive agility, which can lead to a decrease in the productivity of adolescents.6 Anemia adversely affects physical development and jeopardizes the life cycle of women.7,8 Chronic anemia in pregnancy correlates with elevated risks during childbirth and a greater probability of a low-birth-weight infant.6,9
A contributing factor to anemia is insufficient dietary intake.3,10 The predominant causes of nutritional deficiency anemia encompass deficiencies in iron, vitamin A, vitamin B9 (folate), and vitamin B12 (cobalamin).3 Impairment of DNA synthesis can result from deficiencies in folate and vitamin B12, which disrupts the erythropoiesis process and leads to the apoptosis of hematopoietic cells.11,12 Conversely, those with iron deficient anemia exhibited a reduction in hemoglobin and MCV levels.11 In 2021, iron deficiency anemia among women was a significant issue in Southeast Asian countries.2 Iron deficiency is the predominant etiology of anemia, accounting for about 60% of cases.13
Individuals with insufficient dietary intake may suffer from malnutrition. Malnutrition arises from an imbalance in dietary consumption, nutritional status, body tissue mass, and levels of physical activity.14 The nutritional status of teenagers can be assessed by measures such as body mass index (BMI) and mid-upper arm circumference (MUAC). Adolescents with either underweight or overweight status exhibit an increased propensity for developing anemia in comparison to their counterparts with a normal BMI. Furthermore, reduced MUAC measures correlate with a heightened risk of anemia in teenagers.15 Globalization, urbanization, and swift economic development have led to significant alterations in Indonesia’s dietary habits and physical activity levels. Individuals are progressively consuming energy-dense foods while engaging infrequently in physical activity, hence elevating the incidence of overweight and obesity.16 Engaging in physical activity helps mitigate the risk of obesity.17 Mid-upper arm circumference (MUAC) is one of the measures utilized to assess malnutrition,18 which additionally indicates muscular and adipose reserves.19,20 Excess adipose tissue may hinder vitamin absorption and affect erythropoiesis, thereby diminishing red blood cell synthesis.21,22 Moreover, physical activity correlates with muscle mass, indicative of a metabolic state that facilitates erythrocyte production.19,21,22
According to the World Health Organization, 75% of adolescents do not adhere to the minimum physical activity guidelines.23 Physical activity is recognized for its capacity to diminish the risk of obesity and enhance physical fitness and cognitive outcomes.24 Consistent physical activity in children and adolescents correlates with enhanced physical fitness, bolstered immunological function, improved cardiometabolic health, stronger bones, better cognitive results, enhanced mental health, effective weight management, and decreased body fat.25
The World Health Organization (WHO) has implemented measures to mitigate anemia in teenagers by advocating for iron supplementation. This study examines the relationship between dietary intake, physical activity, and anemia in teenagers in light of this guideline. At present, there is a scarcity of research that investigates the combined impact of physical activity and nutritional intake on anemia in adolescent females.
This literature analysis utilizes the scoping review methodology, a technique that identifies and examines knowledge deficiencies and critical attributes or elements related to a concept. Furthermore, we employ this strategy to locate and delineate available evidence.26 We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) standards and utilized the PRISMA flowchart for search stages.27
The objective of this review is to comprehend the significance of physical activity and nutritional intake in the context of anemia in adolescent females. Subsequently, the inquiry becomes, “Is there a correlation between anemia in adolescents, physical activity, and nutritional intake?”
This review centers on adolescents as the target demographic, examining dietary intake and physical activity as key exposures, with iron deficiency anemia as the significant outcome. The review is not limited by geographical constraints and encompasses papers published from 2011 to 2024. To be eligible for inclusion, articles had to satisfy the following criteria: (1) original research articles composed in English, (2) published in indexed journals, and (3) accessible in full text. Studies were omitted if they were duplicates, review articles, theses, dissertations, concentrated on pregnancy, or did not investigate the relationship between dietary intake, physical activity, and anemia.
Upon formulating the study questions, we employed the PICO framework, utilizing customized MeSH terms to obtain search results congruent with the research aims. Following the conversion of MeSH terms into the Boolean format, keywords were produced in this sequence: “adolescent” AND “Nutrient Intake” OR “Dietary Intake” AND “Physical activity” OR “Exercise” AND “Anemia”. Articles were searched from November to December 2024.
We searched the PubMed, Scopus, and ScienceDirect databases. The PRISMA flowchart (Figure 1) was modified to detect publications. This flowchart comprises three phases: identification, screening, and inclusion. In the identification phase (Stage I), the quantity of articles obtained from the database search and the count left after the elimination of duplicates were ascertained. At this step, automation tools were employed to filter articles according to criteria like language (English), full-text availability, classification as research papers, year of publication, and open access status. The screening process (Stage II) entailed categorizing papers based on the study topic and eligibility criteria, utilizing keywords, titles, and abstracts. During the inclusion step (Stage III), all the texts of the retrieved articles were assessed. At this level, authors evaluated papers for review eligibility. The selected literature sources were required to fulfill specific requirements, including publication in indexed journals and possessing a designated journal number and volume. Only papers that fulfilled these criteria were included in the final round of the review process.
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Figure 1 PRISMA flowchart of the article’s selection process from 2011 to 2024.
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The results document data from studies investigating the correlation between nutritional consumption and physical activity with anemia. We identified articles according to their profiles, attributes, demographic data, and results from the statistical studies conducted inside the articles.
A total of 5708 publications were identified by an extensive search of various databases, including PubMed (n = 59), Scopus (n = 103), and ScienceDirect (n = 5546). Six supplementary papers were located through manual citation monitoring, and two articles were obtained from prior literature studies. After eliminating 95 duplicate entries, 5430 articles were discarded based on automated screening criteria, and one item was eliminated for failing to align with the designated keywords. Subsequent to the title and abstract screening, 157 publications were eliminated due to their lack of relevance to the research topic. Additionally, five items were inaccessible owing to access limitations. Of the 27 papers evaluated for eligibility, 13 were rejected for failing to meet the inclusion criteria. In conclusion, 14 papers from databases and additional sources were incorporated into the final review.
Most of the selected papers regarding demographic aspects originated from the Asia-Pacific region (Figure 2). This pertains to undernourishment in the Asia and Pacific subregion. The Food and Agriculture Organization (FAO) reports that despite a reduction in undernourishment by 12 million individuals in 2021, the total number of undernourished people remained 55 million higher than in 2019.28 Early malnutrition is recognized to impede skeletal development and menarche while extending the growth period in females.29 Malnutrition is frequently linked to anemia.30
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Figure 2 Characteristics of selected articles by continent (n = 14).
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We selected attributes based on author names, publication year, country of study, title, objectives, participant data, methodologies, and outcomes. The research characteristics incorporated in this scoping review are delineated in Table 1. The participant count ranged from 47 to 22,486. While the research recruited participants beyond adolescence, the literature specifically encompassed the cohort of adolescent girls. Most of the articles employed a cross-sectional design,10,31–40 an article employing a cohort design41 and two further articles employed retrospective studies.42,43 Four research employed bivariate analysis,32,35,36,38 Ten studies examined utilizing multivariate testing.10,31,33,34,37,39–43 The particular analysis differs based on the data type (Table 2).
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Table 1 The Characteristics of Selected Studies (n = 14)
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Table 2 The Analytical Methods of Selected Studies (n = 14)
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Table 3 presents the study’s findings concerning the correlation between dietary intake, physical activity, and anemia. The analysis revealed that the results pertained to nutritional intake of macronutrients and micronutrients, dietary diversity, energy consumption, and frequency of food intake. The analysis pertains to physical activity through sports club membership, sports participation, standing board jumps, and several nutritional parameters, including participant socio-demographics and average monthly income. A statistical investigation of the correlation between these variables and anemia was conducted using bivariate and multivariate methods.
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Table 3 Summary of the Findings (n = 14)
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Figure 3 shows a network visualization of keywords based on the selected studies. A label and a circle indicate each item. The weight of the item determines the size of the label and circle—the higher the weight, the larger the label and circle. The color of each item indicates the cluster in which the item is located. The lines connecting the items indicate the relationship or association between the items.44 The blue signifies the correlation between iron deficiency anemia and teenage females; the green denotes food consumption in relation to anemia; whilst the red illustrates the association between physical activity and anemia. The map lacks terms about muscle mass and fat mass.
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Figure 3 Map of Keywords Based on Selected Studies. Blue indicates the link between iron deficiency anemia and adolescent girls; green shows dietary intake; red reflects physical activity in relation to anemia.
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Anemia is a nutritional issue that adversely affects the growth and development of adolescent females and is closely linked to their nutritional status.13 A multitude of studies have examined the relationship between adolescent food consumption, physical activity, and anemia; however, only fourteen papers fulfilled the review requirements. The analysis indicated insufficient information about the correlation between nutritional intake, physical activity, and anemia globally (Table 3).
The examined studies assessed macronutrient intake, micronutrient intake, dietary diversity, energy intake, and frequency of food consumption. The physical exercise included sports club membership, various sports, and standing board jumps. We also incorporated additional characteristics about nutrition, including participant socio-demographics and average monthly income. Seven articles indicated a correlation between nutritional intake.10,31,32,40–43 Nonetheless, three investigations indicated that nutritional intake was not substantially associated with anemia.34,35,39 Three studies indicated a strong link in physical activity,36,38,41 two studies revealed no significant link.31,42 Two studies addressed both topics but yielded insignificant analytical results for the physical activity component.31,42
Only one study examined the relationship between dietary consumption, physical activity, and anemia, yielding significant analytical data.41 The results of this review are, however, corroborated by a number of studies. According to a systematic review, motor competence is an indispensable component of a healthy lifestyle, and both a balanced diet and physical activity are beneficial for the health of adolescents.45 This aligns with a study conducted in Portugal, which discovered that physical activity positively corresponds with body–food choice congruence, indicating a propensity to select foods that enhance bodily health and function, such as those that supply energy and stamina.46 Moreover, elevated levels of physical activity correlate with more autonomous eating behaviors, resulting in healthier dietary selections.47
The review indicated a correlation between the intake of both micronutrients and macronutrients and anemia.10,31,32,40,42 Two investigations showed a substantial correlation between the intake of vitamin B12 and folate and the incidence of anemia. Women with anemia had a markedly greater frequency of folate insufficiency than their non-anemic counterparts.32,42 Folate and vitamin B12 collaborate synergistically in creating red blood cells. A shortage in either folate or vitamin B12 impairs DNA synthesis and the erythropoiesis process.12 This aligns with research in India, indicating that anemia is prevalent among adolescent girls with vitamin B12 deficiency.48 A study in Palestine indicated that vitamin C is essential for the metabolism and absorption of iron.32 Iron is crucial for numerous cellular operations, encompassing enzyme activities, DNA synthesis, oxygen transport, and mitochondrial energy generation.4 Ascorbic acid, or vitamin C, facilitates the retention of iron in its reduced state, enhancing its bioavailability for absorption by the body.49 Ascorbic acid significantly improves the absorption of both ferric (Fe3+) and ferrous (Fe2+) iron ions. This results from the reducing characteristics of vitamin C, which maintains iron’s solubility across different pH levels, therefore enhancing its absorption via iron transporters in the small intestine.50
Four studies demonstrated that the intake of protein- and fat-dense meals, such as meat, correlates with a diminished risk of anemia.10,31,32,40 A study in Vietnam indicated a notable rise in hemoglobin and iron levels among participants who received animal-based diets compared to the control group.51 This indicates that meat-based diets assist in averting the reduction of iron levels. One study indicated that a high overall body fat percentage correlates with anemia.36 Excess body fat may hinder vitamin absorption and the erythropoiesis process, thereby affecting red blood cell production,21,22 increased body fat triggers an inflammatory response that elevates hepcidin levels, thereby impairing iron absorption in the gastrointestinal tract.22 Conversely, protein is crucial for the synthesis of hemoglobin and myoglobin. When amino acids for protein synthesis are scarce, the body degrades muscle protein to fulfill amino acid needs. Extended protein shortage results in a reduction in skeletal muscle mass.52 No studies about muscle mass were identified in this review.
A study conducted in India revealed that teenagers suffering from anemia exhibited a higher propensity for poor individual dietary diversity. Dietary diversity and trends are shaped by dietary variety as geographic, cultural, and economic limitations.43 A study in Tanzania indicated that adolescents with suboptimal diet quality exhibited elevated rates of overweight and anemia compared to their counterparts with superior diets. The study revealed that teenagers residing in urban regions exhibited a greater risk of overweight and anemia in comparison to those in rural settings.33 A study in Ethiopia revealed that adolescent females from households with low monthly income were ten times more likely to be anemic.37 This monthly income pertains to energy use. A study conducted in Japan revealed that reduced calorie consumption was inversely correlated with low ferritin levels.41
Physical activity is essential for teenage nutrition.53 Physical activity is recognized to enhance calorie expenditure, aiding in the prevention of obesity,17 reduces body fat,25 and enhances red blood cell volume during youth.53 This study discovered that low to moderate-intensity physical activity correlates with a reduced risk of being overweight compared to a sedentary lifestyle.33 A study conducted in China indicates that moderate to high-intensity physical activity can diminish fat mass.54 Excess adipose tissue can impede vitamin absorption and erythropoiesis, affecting red blood cell synthesis.21 Physical exercise is correlated with muscle mass. Increased muscle mass signifies favorable metabolic health and facilitates the production of healthy erythrocytes.21 In individuals with low exercise intensity, there is a reduction in muscle mass and oxidative capability of the muscles.55 Muscle oxidative capability pertains to mitochondrial oxidative phosphorylation, a mechanism via which the body transforms nutrients into ATP utilizing oxygen.56 In mitochondria, proteins engage with enzymes that facilitate energy production and contribute to the regulation of energy metabolism and erythropoiesis.57
A significant correlation between ferritin and hemoglobin levels and fitness has been seen in females.38 A study indicated a shorter exercise experience correlated with reduced ferritin levels.41 A study in Dubai revealed analogous findings, indicating that students with anemia engaged in less physical activity than their non-anemic counterparts. This study identified a correlation among anemia, insufficient physical activity, and total body fat percentage. This may be associated with a nutritionally deficient diet and a predilection for fast food.36 A study conducted in Palestine revealed no correlation between anemia and physical activity.31 This aligns with a study conducted in Japan, which indicated that the contributor to anemia in long-distance runners is the hepcidin response, which diminishes iron absorption in the gastrointestinal tract.42 This study demonstrated that excessive physical activity may elevate hepcidin levels.
Based on the review, we suspect that adequate food consumption and consistent exercise complement each other in preventing anemia. It is known that adequate nutritional intake by doing exercise is a combination that increases oxidation and restores muscle mass.55,58,59 Physical activity is related to muscle mass, which indicates a metabolic condition that supports erythrocyte formation.21,53,55 We concluded that adequate nutrition and consistent physical activity are crucial in preventing anemia in young women, thereby contributing to optimal quality of life, particularly in preparing for future pregnancy and childbirth.
However, considering the discrepancies in findings on the association between physical activity and anemia, we deduce that specific limitations about the frequency of physical exercise may influence anemia. Additional research is required on this subject. The interplay of adequate energy consumption and physical activity influences the body’s capacity to absorb, retain, and utilize iron effectively. This indicates that a comprehensive approach is essential in preventing anemia. Preventing anemia involves a multifaceted approach rather than concentrating on a singular issue.
This study is advantageous due to the existing paucity of studies on dietary intake and physical activity concerning anemia in adolescent girls. This study possesses multiple drawbacks. We incorporated research including adolescent samples without accounting for their menstrual health and erythrocyte genetics.
Anemia in teenagers is affected by various factors, including nutritional consumption, physical activity, and socioeconomic conditions. Intake of both macronutrients and micronutrients, especially iron, vitamin B12, folate, and vitamin C, is essential for red blood cell production and preventing anemia. Diversity in dietary intake and energy adequacy substantially influence anemic status. Moderate to high-intensity physical activity is favorably correlated with hemoglobin and ferritin levels. Conversely, excessive adiposity and diminished muscular mass can adversely impact erythropoiesis and iron absorption mechanisms. This review indicates that nutritional intake and physical exercise are interconnected and positively affect anemia prevention. Nonetheless, additional research is required to ascertain the precise frequency and duration of physical exercise that affects anemia. Preventing anemia should not depend on isolated interventions. A holistic strategy is required, encompassing sufficient nutritional education, monitoring of nutritional status, provision of iron supplements, and programs promoting physical activity among adolescents. Moreover, governmental measures are essential to guarantee justice, sustainability, and the enduring effects of anemia prevention a single intervention.
The Academic Leadership Grant Universitas Padjadjaran funded the APC.
The authors declare that there are no conflicts of interest in the writing or publishing of this article.
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