On the diabetes-to-stomach side of the model, chronic hyperglycemia is presented as the initiating pressure. Excess glucose overloads mitochondrial electron transport, increases reactive oxygen species and activates pathways including NADPH oxidase. In diabetic animals, the review reports higher concentrations of lipid peroxidation products such as MDA and 4-HNE in gastric mucosa, reduced antioxidant enzyme activity, activation of the NF-κB inflammatory axis, an unfavorable balance between the anti-apoptotic protein Bcl-2 and pro-apoptotic Bax, and activation of caspase-9 and caspase-3. The resulting epithelial apoptosis, impaired cell proliferation and thinned lamina propria provide a plausible route from hyperglycemia to gland loss and mucosal atrophy. This evidence comes primarily from experimental models and does not establish the same sequence in human diabetes.

Advanced glycation end products, or AGEs, add another proposed route. High glucose promotes non-enzymatic glycation of long-lived matrix proteins including collagen and laminin, altering their cross-linking and physical properties. When AGEs engage the receptor for AGEs, or RAGE, they can activate NF-κB and MAPK signaling, stimulate NADPH oxidase and promote further reactive oxygen species. Animal studies summarized in the review associate elevated AGEs with structural disorders, while experimental findings connect RAGE signaling to impaired fibroblast function, reduced collagen synthesis and delayed healing. AGE cross-linking may also make the mucosa less compliant and more vulnerable to acid, bile and Helicobacter pylori. The authors describe this as a positive feedback loop in which oxidative stress and glycation reinforce one another, but they acknowledge that direct longitudinal evidence in patients remains limited.

Diabetes may also compromise the stomach’s blood supply and its capacity to repair. Diabetic microangiopathy affects the small vessels beneath the gastric mucosa, producing endothelial swelling, luminal narrowing, reduced perfusion density and chronic ischemia. The review cites measurements showing lower mucosal blood flow in people with diabetes than in healthy controls and patients with chronic superficial gastritis. Reduced nitric oxide bioavailability, increased asymmetric dimethylarginine and elevated von Willebrand factor can further disturb microcirculation and microthrombosis. Prolonged hypoxia stabilizes HIF-1α, which may initially support adaptation but, when chronically imbalanced, can sustain inflammatory signaling, reduce tight-junction proteins and hinder epithelial regeneration. Deficits in prostaglandin E2, epidermal growth factor and TGF-β signaling are also described as weakening mucus and bicarbonate protection and slowing the reconstruction of damaged epithelium.

Neurological complications add a gastric-motility component. Diabetic autonomic neuropathy can reduce vagal stimulation of acid-secreting parietal cells, disturb the balance between gastrin-secreting G cells and somatostatin-secreting D cells, and impair the protective role of ghrelin. Diabetic gastroparesis is characterized in the review by weak antral contractions, increased pyloric resistance and delayed emptying of solid food. Retention and reflux of bile- and enzyme-rich duodenal contents can damage epithelial tight junctions and cell membranes. Loss or dysfunction of interstitial cells of Cajal, the stomach’s electrical pacemaker cells, further disrupts contractions, and experimental work links oxidative stress, microvascular injury, pro-inflammatory macrophages and altered autophagy to their decline. Together, delayed emptying, bile reflux, mucosal injury, cellular loss and worsening motility are proposed to form a self-reinforcing sequence that can progress from chronic inflammation to gland atrophy and intestinal metaplasia.

Helicobacter pylori provides a potential meeting point between hyperglycemia, infection and atrophy. The review describes altered glycosylation of gastric mucins in a high-glucose environment, which may expose structures that improve bacterial adhesion, together with reduced acidity that weakens the stomach’s chemical defense. Diabetes-associated impairment of neutrophil chemotaxis, phagocytosis and intracellular killing may make early clearance less effective, while macrophage responses become more strongly skewed toward inflammation. H. pylori can also induce the immunosuppressive cytokine IL-37 through receptors including TLR2, TLR4 and NOD1. Its virulence factors, notably CagA from cag-positive strains, can amplify NADPH oxidase activity, oxidative damage and NF-κB signaling, potentially accelerating the sequence from gastritis to atrophy and metaplasia. These observations suggest that infection, immune dysfunction and high glucose may cooperate, but they do not show that every patient with diabetes follows this course or that eradication alone prevents atrophy.

In the reverse direction, atrophic gastritis may disturb glucose metabolism through several partially overlapping mechanisms. Loss of parietal cells reduces gastric acid and intrinsic factor, impairing the release and terminal-ileal absorption of vitamin B12 and reducing the conversion of dietary iron to a more soluble form. B12 deficiency can lead to hyperhomocysteinemia, which has been associated with oxidative stress, endothelial injury and insulin resistance. Preclinical evidence also links homocysteine to endoplasmic-reticulum stress, mitochondrial dysfunction and apoptosis in pancreatic beta cells. Iron deficiency may restrict mitochondrial complex IV activity and ATP production in insulin-sensitive tissues, potentially worsening insulin signaling and glucose-stimulated insulin secretion. These pathways are biologically coherent, but the review notes that much of the evidence is preclinical and that trials demonstrating improved glycemic control after correction of atrophic-gastritis-related deficiencies are scarce.

Changes in the gastric endocrine network offer a second potential route. Loss of acid removes negative feedback on antral G cells, producing marked hypergastrinemia, while impaired D-cell function may weaken somatostatin inhibition. Although moderate gastrin elevations can have metabolic or trophic effects under physiological conditions, the review proposes that sustained supraphysiological stimulation of CCK-B receptors on beta cells may desensitize insulin secretion, deplete functional reserves and interfere with beta-cell transcription factors. Atrophic gastritis affecting the gastric body and fundus can also destroy X/A-like cells, the main source of ghrelin, altering meal-related hunger signals and potentially removing ghrelin’s inhibitory influence on basal insulin secretion. Because ghrelin also affects skeletal-muscle mitochondrial function and inflammation, its loss may intersect with diabetic sarcopenia and insulin resistance. These consequences remain mechanistically inferred rather than demonstrated by prospective hormone-intervention trials.

Low gastric acidity can also permit small intestinal bacterial overgrowth, altering microbial metabolites and the gut-liver-pancreas axis. Lipopolysaccharide from Gram-negative bacteria may enter portal circulation, activate TLR4 and inflammatory pathways such as JNK and IKK/NF-κB, and contribute to systemic insulin resistance. Changes in short-chain fatty acids and bile-acid metabolism may affect intestinal barrier integrity and the incretin hormones GLP-1 and GIP. The review reports associations between overgrowth, dysbiosis, irregular glucose regulation and reduced post-meal incretin responses, but notes that microbial and short-chain-fatty-acid responses can be complex and cannot be reduced to a single pathway. A major shared mechanism in the proposed cycle is disruption of the PINK1/Parkin mitophagy pathway: experimental findings associate high glucose and inflammation with reduced Parkin activity, damaged mitochondrial accumulation, impaired autophagic flux and apoptosis in both gastric epithelium and pancreatic beta cells, while leaked mitochondrial DNA can further activate STING and NF-κB signaling.

The review also identifies a shared immune and genetic background. HLA class II haplotypes such as DR3-DQ2 and DR4-DQ8 have been associated with susceptibility to both diseases, while anti-islet, anti-parietal-cell and intrinsic-factor antibodies occur in subsets of patients with diabetes. An imbalance between pro-inflammatory Th17 cells and regulatory T cells is another proposed link, with IL-17A activating NF-κB and STAT3-driven differentiation potentially contributing to injury of both gastric parietal cells and pancreatic beta cells. Yet the authors are explicit that none of the principal connecting nodes has been validated in a large prospective interventional study of comorbid patients. They call for longitudinal cohorts that repeatedly measure glucose control, gastroscopy, mucosal histology and biomarkers; dual-disease animal models and patient-derived gastric organoids; and simultaneous profiling of gastric and metabolic pathways. The review’s proposed antioxidant, hormonal, microecological and autophagy-based interventions are consequently early-stage research directions, not proven treatments for breaking the diabetes–gastritis cycle.

Subject of Research: Proposed bidirectional mechanisms linking diabetes mellitus and atrophic gastritis

Article Title: Diabetes mellitus and atrophic gastritis: progress in the study of interactive pathogenesis

Article References: Zhu, Z., Wang, L., Zhou, T., Che, Y., Shi, Y., Song, J., Zhang, Z., Xu, J., Tian, S., Qu, N., Lu, Y., Hao, Y., Zhang, J., Gao, H., & Lv, H. (2026). Diabetes mellitus and atrophic gastritis: progress in the study of interactive pathogenesis. Frontiers in Endocrinology, 17, Article 1955709. https://doi.org/10.3389/fendo.2026.1955709

Image Credits: AI Generated

DOI: 10.3389/fendo.2026.1955709

Keywords: diabetes mellitus, atrophic gastritis, hyperglycemia, gastric mucosa, oxidative stress, gut microbiome, insulin resistance, vitamin B12, gastroparesis, Helicobacter pylori, Diabetes, mellitus

Celiac disease is a chronic, immune-mediated enteropathy that develops in genetically susceptible individuals after exposure to dietary gluten. The immune assault flattens the villi of the small intestine, deepens the crypts, and floods the mucosa with intraepithelial lymphocytes, producing a structural injury that impairs the absorption of several micronutrients. In adults the disease often presents with nonspecific symptoms, biochemical abnormalities, or isolated anemia, and micronutrient deficiencies may persist despite diagnosis and dietary treatment. Because chronic inflammation can disturb iron homeostasis through hepcidin-mediated pathways, while persistent deficiencies may in turn sustain low-grade inflammatory activity, the interaction between systemic inflammation and nutritional status is complex and not yet fully clarified.

The indices at the center of the study are derived from complete blood count parameters that are measured routinely in every patient. The SII integrates neutrophil, lymphocyte, and platelet counts into a single composite parameter calculated as platelet count multiplied by neutrophil count divided by lymphocyte count, and it was selected as the primary inflammatory index because it captures three peripheral blood cell populations rather than two. The NLR and PLR, which are based on two-cell ratios, were included as established comparator indices. All three have attracted growing interest as measures of systemic immune-inflammatory activity in chronic inflammatory and autoimmune disorders, but data on SII in celiac disease, particularly in relation to nutritional parameters, remain limited.

The researchers evaluated the indices according to ferritin, transferrin saturation, vitamin B12, folate, and vitamin D status. Ferritin and transferrin saturation were chosen to assess iron status because they provide complementary information on iron stores and functional iron availability, particularly in the presence of chronic inflammation. Vitamin B12 and folate were included because deficiencies may result from impaired intestinal absorption and are associated with hematological and neurological complications, whereas vitamin D was evaluated because of its established role in bone metabolism and immune regulation. Deficiencies were defined using the hospital laboratory’s reference ranges: ferritin below 15 ng/mL, transferrin saturation below 20%, vitamin B12 below 200 pg/mL, folate below 4 ng/mL, and 25-hydroxyvitamin D below 20 ng/mL.

The cohort was predominantly female, with 79 of the 120 patients (65.8%) being women, and the mean age was 35.3 years. The median disease duration was 9 years, and 90% of patients were documented as adherent to a gluten-free diet. Anemia, defined by World Health Organization criteria, was present in 20.8% of patients. Micronutrient deficiency rates were striking: 32.5% of patients with available ferritin measurements had ferritin levels below 15 ng/mL, 54.8% had transferrin saturation below 20%, 12.2% had vitamin B12 deficiency, 22.1% had folate deficiency, and 68% had vitamin D deficiency. Patients receiving active iron, vitamin B12, or folate replacement therapy at the time of laboratory assessment were excluded to minimize confounding.

The most consistent associations were observed for iron status. Patients with ferritin deficiency had higher SII, NLR, and PLR values, and all three differences remained statistically significant after Holm correction (SII: Holm-adjusted p = 0.025; NLR: p = 0.049; PLR: p = 0.007). Spearman correlation analysis demonstrated a modest inverse correlation between serum ferritin levels and SII (ρ = −0.23, p = 0.013), indicating that higher SII values tended to be associated with lower ferritin concentrations. In contrast, patients with low transferrin saturation showed higher SII and NLR values in unadjusted analyses, but these associations did not remain significant after correction for multiple comparisons.

Vitamin B12 deficiency was associated with higher SII and NLR values in unadjusted analyses, but neither association survived the Holm correction. Exploratory analyses using Firth penalized logistic regression and treating vitamin B12 as a continuous outcome nevertheless suggested a possible relationship, with an adjusted odds ratio of 1.97 per doubling of SII (95% CI, 1.05–3.92; p = 0.033). Given the small number of vitamin B12-deficient patients, only 13 or 14 depending on the analysis, the researchers considered this finding exploratory rather than confirmatory. No associations were detected between the inflammation indices and folate or vitamin D deficiency after correction for multiple comparisons, with all Holm-adjusted p values reaching 1.000.

The biological interpretation is nuanced. Ferritin reflects body iron stores but may also be influenced by inflammatory activity, whereas transferrin saturation more directly reflects circulating iron availability. Higher SII in patients with low ferritin levels may therefore not solely reflect iron depletion itself but rather the persistent inflammatory milieu accompanying active celiac disease. Conversely, iron deficiency itself may influence neutrophil, lymphocyte, and platelet counts, thereby contributing to changes in composite indices such as SII. The observed association is likely to reflect the combined effects of persistent mucosal inflammation and hematological alterations related to iron deficiency rather than a single underlying mechanism. Factors unrelated to systemic inflammation, including menstrual blood loss, dietary iron intake, and occult gastrointestinal bleeding, may also influence ferritin concentrations.

The absence of associations with vitamin D and folate is not entirely unexpected, as the determinants of these micronutrients extend beyond intestinal absorption and inflammatory activity. Vitamin D status is influenced by sunlight exposure, dietary intake, supplementation, and seasonal variation, while folate levels may be affected by nutritional habits and replacement therapy. The circulating concentrations of these micronutrients are therefore determined by a broader range of factors than systemic inflammatory activity alone. The findings suggest that not all micronutrient abnormalities in celiac disease are equally associated with systemic inflammatory indices, with the most consistent associations observed for reduced iron stores.

The researchers emphasize that the present findings should be interpreted as evidence of association rather than clinical utility. The study was not designed to evaluate the diagnostic performance of SII or its incremental value over conventional hematological parameters such as hemoglobin, mean corpuscular volume, and red cell distribution width, and no formal comparisons of discriminatory performance among SII, NLR, and PLR were performed. The retrospective, single-center design limits causal inference and generalizability, information on serological activity and histopathological severity was not consistently available, and the cross-sectional nature precludes assessment of temporal relationships. Because the majority of patients were adherent to a gluten-free diet and under long-term follow-up, the observed inflammatory indices reflect the inflammatory status during treated follow-up rather than at the time of initial diagnosis. Larger prospective cohorts are needed to confirm these associations and to determine whether inflammation-based indices derived from routine blood counts can eventually serve a clinical role in monitoring micronutrient status in adults with celiac disease.

Subject of Research: Systemic inflammation indices, particularly SII, are associated with reduced iron stores in adults with celiac disease.

Article Title: Association of systemic inflammation indices with micronutrient status in adult patients with celiac disease

Article References: Candan, S., Katı, O., Eşkazan, T., Bakkaloğlu, O. K., Hatemi, İ., Dobrucalı, A. M., & Canbakan, B. (2026). Association of systemic inflammation indices with micronutrient status in adult patients with celiac disease. Frontiers in Medicine, 13, Article 1898592. https://doi.org/10.3389/fmed.2026.1898592

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1898592

Keywords: celiac disease, systemic immune-inflammation index, iron deficiency, ferritin, vitamin B12, micronutrient status, inflammation indices, gastroenterology, Association, systemic, inflammation, indices

The research, conducted entirely in silico using advanced quantum chemical methods, modeled the behavior of Mg(II), Fe(II), Fe(III), Co(II), Co(III) and Cu(II) porphyrines under static magnetic fields ranging from 0.1 to 100 Arbitrary Magnetic Field Units, where one AMFU exceeds 1000 Tesla. The team used density functional theory with the B3LYP functional and a 6-31G** basis set, drawing initial structures in Fujitsu Scigress 2.0, optimizing them in Gaussian 0.9, and then applying the Amsterdam Modelling Suite with a non-relativistic orbital momentum L-dot-B method to simulate the field’s influence before recalculating structural and electronic properties.

The results reveal a consistent pattern: static magnetic fields decreased the stability of every metalloporphyrine examined. The researchers measured this through heat of formation, where less negative values indicate reduced stability. Across all six metal centers, the heat of formation became progressively less negative as flux density increased. For Mg(II) porphyrine, considered a simplified model of chlorophyll, the value shifted from -803 kJ·mol⁻¹ at zero field to -698 kJ·mol⁻¹ at 100 AMFU when the molecule was oriented along the X-axis. The effect depended strongly on how the molecule sat within the Cartesian coordinate system, with X-axis orientation generally producing the strongest destabilization, followed by Y- and Z-axes.

Alongside the loss of stability came a rise in dipole moment, signaling growing molecular asymmetry. The macrocyclic ring, normally flat with D4h symmetry, lost its planarity under the field’s influence. The deformed skeletons adopted one of four characteristic conformations: saddle, ruffle, dome or wave. In Mg(II) porphyrine specifically, the central magnesium atom was ejected from the molecular center as Mg-N bond lengths increased, stretching from roughly 1.9 Å at zero field to over 2.4 Å at the highest flux density along the X-axis.

The electronic consequences were equally significant. Charge density at the ring nitrogen atoms changed irregularly with increasing field strength, and the Mg-N bonds, described as intermediate between ionic and atomic in character, weakened as the external magnetic field reduced the durability of the binding electron pair. The positive charge on the central magnesium atom rose with flux density, which the authors note should enhance its ability to bind Lewis bases and potentially promote photosynthesis, provided the reaction site is not obscured by steric hindrance from the deformed ring.

Iron porphyrines, representing heme and hemin, showed their own distinct responses. The Fe(II) molecule was already non-planar before any field was applied, and the static magnetic field deepened its deformation. Remarkable elongation of some C-H bonds occurred at 10 and 100 AMFU when the molecule sat in the X-Y plane. The positive charge density at the iron atom generally decreased with increasing flux density along the X-axis but increased along the Z and Y axes, a pattern the authors describe as beneficial for accepting Lewis bases such as carbon monoxide. Fe(III) porphyrine, by contrast, resisted deformation more effectively along the X and Z axes, though its iron atom also showed irregular charge shifts and its N-Fe bonds generally lengthened with rising field strength.

Cobalt porphyrines, the structural basis of vitamin B12, behaved differently again. The Co(II) atom, being bidentate, largely inhibited the bending deformation seen in other metalloporphyrines, instead producing local distortion within the macrocycle. When the field acted along the Z-axis, the molecule flattened, cycling through dome-flat-flat-dome conformations as flux density increased. Along the X or Y axis, a wave-mode deformation emerged. Notably, the positive charge density at the Co(II) atom always increased relative to the field-free state, enhancing its capacity to bind Lewis bases, with Y-axis orientation producing the most reactive configuration. The Co(III) cation, however, moved in the opposite direction: field exposure decreased its ability to coordinate Lewis bases, and its presence favored elongation of C-H bonds to a degree suggesting possible dissociation.

Cu(II) porphyrine, the model for hemocyanin in blue-blooded invertebrates, presented perhaps the most unusual behavior. Even without any applied field, both nitrogen atoms bound to copper carried positive charge density, a rarity among the molecules studied. A field of just 0.1 AMFU flipped the charge at N1 to negative when the molecule was oriented along the X or Z axis, while the Y-axis orientation required the full 100 AMFU to achieve the same conversion. The positive charge on the copper atom itself invariably increased with field strength, which should facilitate coordination of Lewis bases, though the N-Cu bond lengths varied irregularly and were least sensitive to elongation along the Z-axis.

Ranking the six metalloporphyrines by stability loss under the field, the order from most to least affected was Fe(III)⁺, Co(III)⁺, Fe(II), Co(II), Cu(II) and Mg(II). The authors conclude that static magnetic fields, even at the lowest simulated flux density of 0.1 AMFU, influence the biological role of metalloporphyrines through changes in electron density at the central metal atoms, steric hindering of the deformed ring, and polarization of bonds from pure valence character toward ionic character. Regardless of orientation along the X, Y or Z axes, the field always destabilized the molecules, and the resulting deformation facilitated additional ligation of the central metal atom, an effect the researchers suggest could potentially be harnessed in synthetic modifications of metalloporphyrines.

The findings carry a speculative connection to astrophysics. The authors note the recent discovery of the highest-energy cyclotron resonance scattering feature from the galactic ultraluminous X-ray pulsar Swift J0243.6+6124, where magnetic fields exceed 1.6 billion Tesla near the surface of the neutron star. Such extreme fields, they argue, reinforce the plausibility that high-density static magnetic fields genuinely deteriorate metalloporphyrine integrity, lending cosmic-scale weight to the computational predictions. While the simulations remain theoretical and the Arbitrary Magnetic Field Unit vastly exceeds typical terrestrial exposures, the work opens a provocative question about whether the magnetic environments surrounding living systems, from MRI scanners to planetary fields, might subtly reshape the chemistry of life’s most essential metal complexes.

Subject of Research: Numerical simulation of static magnetic field effects on biologically essential metalloporphyrines

Article Title: Potential risk resulting from the influence of static magnetic field upon living organisms. Numerically simulated effects of the static magnetic field upon metalloporphyrines

Article References: Ciesielski, W., Girek, T., Oszczęda, Z., Soroka, J. A., & Tomasik, P. (2022). Potential risk resulting from the influence of static magnetic field upon living organisms. Numerically simulated effects of the static magnetic field upon metalloporphyrines. BioRisk, 18, 115-132. https://doi.org/10.3897/biorisk.18.86616

Image Credits: AI Generated

DOI: 10.3897/biorisk.18.86616

Keywords: static magnetic field, metalloporphyrines, porphine, chlorophyll, heme, vitamin B12, hemocyanin, density functional theory, molecular deformation, charge density, BioRisk, computational chemistry

The research team, led by Sarah L. H. Kamhout of the Department of Psychology at Brigham Young University, recruited 80 adolescents between the ages of 14 and 18 from the general community. Participants completed detailed 24-hour dietary recalls using the National Cancer Institute’s Automated Self-Administered 24-hour dietary assessment tool, known as ASA-24, on two to three randomly assigned days that included both weekdays and weekends. The tool captured intake of 26 different micronutrients, ranging from familiar players like calcium, iron, and vitamin D to less-studied carotenoids such as lycopene, lutein, and zeaxanthin. Participants were notified of their assigned recall day only on the day itself, a design choice intended to prevent them from altering their eating habits in response to being observed.

Sleep was measured with unusual rigor for a study of this kind. Each participant wore a wrist-worn actigraph for 7 to 20 days, providing objective data on sleep onset time, sleep midpoint, total sleep duration, sleep efficiency, and wake after sleep onset, a measure known as WASO. Because adolescents are known to be unreliable reporters of their own sleep habits, actigraphy readings were cross-verified with daily sleep diaries. The Sadeh algorithm, a validated method for converting movement data into sleep-wake states, was used to score each night. Sleep efficiency was calculated as the ratio of time asleep to time in bed, and all time-based variables were converted to minutes after midnight to avoid circular calculations.

Beyond nightly sleep, the study also probed more trait-like dimensions of sleep health. Participants completed the Morningness-Eveningness Questionnaire to assess chronotype, their innate preference for early or late sleep and wake times, and the Epworth Sleepiness Scale for Children and Adolescents to gauge daytime sleepiness. Most notably, each subject underwent a six-hour dim light melatonin onset protocol, or DLMO, in the laboratory. After a three-to-five-day at-home sleep stabilization period, saliva samples were collected every 30 to 45 minutes under light levels below 5 lux, beginning five hours before and ending one hour after each participant’s preferred bedtime. DLMO was defined as the moment salivary melatonin concentrations exceeded 4 picograms per milliliter, a threshold previously validated in adolescents. The gap between DLMO and average sleep onset, called the phase angle, served as a measure of circadian alignment, with values between two and four hours considered clinically aligned.

The statistical approach was equally careful. Because dietary reference intakes differ between males and females due to distinct biological and metabolic needs, all analyses were performed separately by sex. The researchers used mixed effects models with random by-participant intercepts to account for multiple dietary intakes per participant, then applied backwards step-wise model fitting to remove micronutrients that did not improve overall model fit. Variance inflation factors below five confirmed low collinearity in all final models, and p-values were corrected for multiple comparisons using the Benjamini-Hochberg false discovery rate procedure, applied separately for daily and averaged models.

Against the researchers’ initial hypotheses, no single micronutrient emerged as significantly associated with improved sleep health across all models. Yet two nutrients showed the most consistent positive signals. Potassium, with coefficients ranging from -0.03 to 0.004 and p-values below 0.05, was linked to increased same-night sleep efficiency in both males and females, and to earlier sleep onset in females. Retinol, a specific chemical form of vitamin A, showed associations with better sleep efficiency in females and earlier sleep midpoint and onset in males, with coefficients ranging from -0.20 to 0.01 and p-values below 0.05. These findings echo a classic double-blind, placebo-controlled crossover study in nine adult males on potassium-deficient diets, where supplementation improved sleep efficiency and consolidation, and more recent work linking lower urinary potassium excretion to greater daytime sleepiness in adults.

On the other side of the ledger, zinc and vitamin B12 were the micronutrients most consistently linked with negative sleep outcomes. Zinc, with coefficients ranging from -0.54 to 3.51 and p-values below 0.10, was associated with later sleep onset in males on the same night, reduced average sleep efficiency in males, and increased daytime sleepiness in both sexes. Vitamin B12, with coefficients ranging from -0.96 to 7.22 and p-values below 0.05, was linked to later sleep midpoint in males, reduced sleep efficiency in females, and increased wake after sleep onset in males. Notably, mean vitamin B12 intake in the sample surpassed the recommended daily allowance roughly three-fold for males and five-fold for females, a pattern consistent with prior research suggesting vitamin B12 can have an alerting effect that delays sleep onset and shortens sleep duration.

The dietary data itself revealed a troubling picture of adolescent nutrition. Less than 2 percent of youth ages 14 to 18 meet recommended vegetable intake guidelines according to national survey data, and only 2.9 percent of children and adolescents meet daily whole grain requirements. In this sample, average intake of sodium, copper, selenium, vitamin C, niacin, vitamin B6, vitamin K, and vitamin B12 exceeded recommended daily intake ranges for both sexes, while average intake of calcium, magnesium, potassium, vitamin D, and vitamin A fell below recommended ranges. Over half of participants did not meet recommended vitamin D intake, a deficiency consistently associated with decreased sleep duration and poorer sleep efficiency in children and adolescents. Iron, frequently tied to sleep disorders such as restless legs syndrome in prior research, showed no significant associations in this study, possibly because the female sample was on average below the recommended daily allowance for iron, making it difficult to detect effects of adequate or excess consumption.

The researchers emphasize that their findings are exploratory signals rather than established causal relationships. The cross-sectional design limits causal inference, though the day-to-night matching of dietary intake with same-night sleep helps establish temporal precedence in some analyses. Self-reported dietary recalls introduce potential recall and desirability biases, and the ASA-24, while demonstrating strong agreement with interviewer-administered recalls, is not a perfect measure of true intake. Absorption and metabolism of micronutrients also vary by individual, influenced by storage levels, interactions between nutrients, and whether intake comes from food or supplements. Carotenoids, for instance, are absorbed less efficiently than retinol, and people with low stores of vitamins A, calcium, and iron increase their ability to absorb more of these nutrients, meaning individual adolescents may have exhibited different patterns of absorption related to their specific consumption patterns.

Despite these limitations, the study represents the first broad examination of micronutrient intake and sleep health in adolescents, a population where nearly 70 percent fail to obtain the recommended 8 to 10 hours of sleep and over 40 percent report sleeping less than 7 hours per night. The findings suggest that sleep may be sensitive to day-to-day shifts in potassium intake, that different chemical forms of vitamin A may play distinct roles in sleep timing, and that zinc and vitamin B12 warrant closer scrutiny for their potential negative associations with sleep during adolescence. The researchers call for experimental and longitudinal designs to clarify causal pathways and for interventions tailored to individual intake patterns, timing of consumption, and interactions between multiple nutrients. No universal, one-size-fits-all dietary solution for improving adolescent sleep emerged from this work, but the study opens a promising avenue for understanding how the food on a teenager’s plate might ripple through the architecture of their night.

Subject of Research: Nutrition and Sleep Science

Article Title: In search of vitamin sleep: cross-sectional analysis of vitamin and mineral intake and sleep health outcomes in adolescents

Article References: Kamhout, S. L. H., Bellini, S. G., Luke, S. G., Homer, K. J., Broadbent, M., & Duraccio, K. M. (2026). In search of vitamin sleep: cross-sectional analysis of vitamin and mineral intake and sleep health outcomes in adolescents. Frontiers in Nutrition, 13, Article 1978612. https://doi.org/10.3389/fnut.2026.1978612

Image Credits: AI Generated

DOI: 10.3389/fnut.2026.1978612

Keywords: adolescent sleep, micronutrients, potassium, retinol, zinc, vitamin B12, circadian rhythm, DLMO, actigraphy, sleep health, search, vitamin

The biochemistry of cobalamin explains why deficiency matters so much. Vitamin B12 is a water-soluble vitamin synthesized only by microorganisms, and it is found almost exclusively in animal-derived foods such as red meat, fish, eggs, and milk, with a very small contribution from foods or water exposed to B12-producing bacteria. Within the body, cobalamin serves as a critical cofactor in two reactions: the conversion of homocysteine to methionine via methionine synthase, and the conversion of methylmalonyl-CoA to succinyl-CoA via methylmalonyl-CoA mutase. These reactions make the vitamin essential for DNA synthesis, red cell production, and the maintenance of nerve myelin. Deficiency can therefore manifest as megaloblastic anemia and glossitis, peripheral neuropathy, subacute combined degeneration of the spinal cord, and cognitive impairment. In pregnancy, low maternal B12 has been associated with neural tube defects and other adverse birth outcomes, as well as longer-term metabolic risk in the offspring.

The life-course pattern reported in India is striking. According to the CNNS, the first nationally representative estimate of pediatric B12 status, deficiency affects 13.8 percent of pre-school children aged 1 to 4 years and 17.3 percent of school-age children aged 5 to 9 years, with little difference between boys and girls at these ages. The rate roughly doubles in adolescence: 31.0 percent of adolescents aged 10 to 19 years were deficient in the CNNS, and a pooled meta-analytic estimate for the 0 to 17-year age band was higher still, at 57 percent, though based on fewer studies and a wider confidence interval. Among adults, the pooled prevalence across the largest meta-analysis was 48 percent, with a 95 percent confidence interval of 35 to 62 percent, and one Indian study reported deficiency as high as 78.5 percent in healthy adults depending on the serum cut-off used. Among the elderly, a review of Indian adults reported 61.7 percent deficiency using varied cut-offs, and hospital series show diagnosed cases increasing with age and peaking around 50 to 65 years.

Pregnant women represent a particularly vulnerable group. A synthesis of 46 studies on B12 status among pregnant and lactating women in India found deficiency prevalence ranging from 40 to 70 percent, and a meta-analysis estimated that approximately 67 percent of pregnant women are affected. International meta-analyses have similarly found insufficient B12 during pregnancy to be common globally and associated with lower birth weight. In Indian cohorts, low maternal B12 alongside adequate-to-high folate has been associated with neural tube defects, recurrent pregnancy loss, gestational diabetes, pre-eclampsia, intrauterine growth restriction, and adverse metabolic and cognitive outcomes in the child, although the review emphasizes that these data derive from observational cohorts and should be interpreted as associations rather than demonstrated causal pathways. The risk persists into lactation, since low maternal stores lower breast-milk B12 and place exclusively breastfed infants at risk, yet current Indian antenatal policy supplements only iron and folate, not vitamin B12.

Diet is the single most important determinant of B12 status in India. Individuals consuming a lacto-vegetarian diet, a substantial share of the Indian population, have significantly lower cobalamin levels than those consuming a mixed diet, and reviews consistently show several-fold higher deficiency among lacto-vegetarians than non-vegetarians. In one study of healthy young vegetarian adults, approximately 50 percent had serum B12 below the deficiency threshold, 70 percent of men and 50 percent of women had low holotranscobalamin, and 92 percent of men and 50 percent of women had hyperhomocysteinaemia. Dietary insufficiency, not pernicious anemia, is the dominant cause of B12 deficiency in India, reflecting the combined effects of a largely cereal-based lacto-vegetarian diet, low consumption of animal-based foods, and high rates of poverty. Beyond diet, the most consistently reported associated factors are low socioeconomic status, advancing age, and female sex, with age-related malabsorption from atrophic gastritis, reduced gastric acid secretion, and Helicobacter pylori infection adding to the burden among older adults.

Regional heterogeneity within India is substantial. In the CNNS, B12 deficiency prevalence was highest in the central region of India across every pediatric age band assessed: 21.0 percent in pre-schoolers, 29.1 percent in school-age children, and 42.7 percent in adolescents, each substantially above the corresponding national estimates. Despite this marked regional gradient, the same survey found no consistent difference in B12 deficiency between rural and urban locations at the national level, a pattern that sits alongside inconsistent rural/urban findings from individual state-level studies. Studies from Pune comparing middle-aged men in rural, slum, and middle-class urban settings found a high frequency of low B12 across all three settings, with rural and slum residents faring worse than urban middle-class residents, suggesting that dietary intake and socioeconomic status appear to be stronger determinants of B12 status than geographic setting per se.

Outside India, B12 deficiency follows clear geographic and economic lines. High-income populations with adequate access to animal-source foods have lower deficiency prevalence, while low- and middle-income populations are more affected owing to both scarcity of animal-source foods and a higher burden of malabsorptive conditions. A widely cited compilation of national and regional datasets found serum B12 deficiency in 11 to 15 percent of women in Germany and the United Kingdom, 31 percent of elderly individuals in the UK, 49 percent of adults in India, 40 percent of children in Kenya, 28 percent of pregnant women in Nepal, and 20 percent of the same demographic group in New Zealand. In Latin America and the Caribbean, an analysis of 41 studies suggested up to 61 percent of individuals in Mexico and Central/South America had inadequate B12 stores. In sub-Saharan Africa, available national micronutrient surveys indicate 54 percent, 35 percent, and 15 percent B12 deficiency among reproductive-age women in Malawi, Kenya, and Ethiopia respectively, with a lower prevalence of 7 percent in Ghana. The Indian subcontinent and neighboring South Asian countries report the highest deficiency prevalence worldwide, 70 to 80 percent in some series, primarily reflecting a predominantly vegetarian, carbohydrate-based diet.

A key constraint on reconstructing a 50-year trend is that no single longitudinal, nationally representative cobalamin survey exists in India, or indeed anywhere else, spanning this period. Most available estimates are cross-sectional snapshots using different biomarkers, cut-offs, and populations. Evidence from the 1970s and 1980s was largely clinical and descriptive, with early recognition that asymptomatic Indian lacto-vegetarians had lower B12 than non-vegetarian counterparts and observations of anemia among Asian immigrants in London raising the possibility of a population-level problem. Systematic biochemical assessment began at the turn of the millennium with the Pune studies, which documented a high prevalence of low cobalamin with concomitantly elevated homocysteine across sampled Indian populations. Since 2000, the evidence base has grown substantially, with clinic and community studies through the 2010s consistently showing an adult prevalence of approximately 47 percent, the CNNS providing the first national pediatric and adolescent estimates, and two independent meta-analyses synthesizing studies to 2020 and 2023 reporting pooled adult prevalence of 51 to 53 percent. A large 2024 health-check dataset of over 15,000 asymptomatic adults across seven northern Indian states reported a considerably lower figure of 24.2 percent, which most plausibly reflects a higher serum cut-off and a more affluent, urban, self-selected sample rather than a genuine decline in burden.

A limitation running through every prevalence estimate cited in the review is the absence of biomarker and cut-off harmonization. Total serum/plasma B12 thresholds used across the cited studies range from below 150 pmol/L to below 211 pg/mL, and most studies rely on total B12 rather than on functional markers such as holotranscobalamin or methylmalonic acid, which more directly reflect tissue cobalamin status. Total serum B12 is itself an indirect marker that can be influenced by recent dietary intake, by pregnancy-related haemodilution, and by inter-laboratory assay variability. A concrete illustration of the resulting inconsistency comes from a single cohort of healthy young Indian vegetarians, in which roughly 50 percent were deficient by total serum B12, but 70 percent of men and 50 percent of women had low holotranscobalamin, and 92 percent of men and 50 percent of women had hyperhomocysteinaemia, meaning a 20-percentage-point-or-greater spread in deficiency depending solely on which biomarker was used. Consequently, differences between surveys, such as the 24.2 percent from the 2024 health-check sample versus 51 to 53 percent from pooled meta-analyses, are driven substantially by differences in cut-points, biomarkers, and sampling frames in addition to any true temporal change.

The review concludes that vitamin B12 deficiency is a largely preventable, straightforward-to-treat disorder whose continued neglect in India’s public health programming is difficult to attribute to anything other than insufficient prioritization relative to its documented scale. From a public health perspective, the authors call for harmonized diagnostic criteria for B12 deficiency, ideally combining total circulating B12 with a functional marker such as holotranscobalamin or methylmalonic acid, and routine screening particularly for pregnant and lactating women, adolescents, the elderly, and strict vegans and vegetarians. Evidence-based strategies to reduce the burden include dietary diversification, food fortification, and the addition of B12 to existing antenatal and adolescent supplementation programmes, which currently contain only iron and folic acid. On fortification specifically, the evidence is directionally supportive but implementation-dependent: India’s current 2018 FSSAI fortification standards for folic acid and vitamin B12 are set at roughly 90 percent below WHO-recommended levels for Indian consumption patterns, having been lowered from stronger 2016 standards, and a recent review identifies concrete barriers to more effective scale-up, including uneven regulatory enforcement, continued reliance on voluntary fortification of open-market atta, variable miller-level capacity and quality assurance, and insufficient long-term monitoring of nutritional outcomes among beneficiaries. Large-scale staple fortification has also drawn published concerns from Indian public-health researchers regarding the strength of the underlying evidence base and potential safety considerations at higher fortification levels, so any revision of national standards should be accompanied by the monitoring and evaluation infrastructure needed to track both benefit and safety at population scale. Regional data gaps, particularly the absence of CNNS-scale state-level surveillance in adults, should also be prioritized in future national nutrition surveys.

Subject of Research: Vitamin B12 deficiency epidemiology in India and worldwide

Article Title: Vitamin B12 deficiency: epidemiological trends and risk factors

Article References: Toteja, G. S., & Toteja, N. (2026). Vitamin B12 deficiency: epidemiological trends and risk factors. Frontiers in Nutrition, 13, Article 1930037. https://doi.org/10.3389/fnut.2026.1930037

Image Credits: AI Generated

DOI: 10.3389/fnut.2026.1930037

Keywords: vitamin B12, cobalamin, micronutrient deficiency, India, epidemiology, vegetarian diet, pregnancy, food fortification, Vitamin, deficiency, epidemiological, trends

The trial enrolled ninety patients with focal, mechanically caused peripheral nerve injuries — the kind produced by crush trauma, traction, lacerations, or chronic compression syndromes such as carpal tunnel and cubital tunnel disorder. Participants were randomly divided into three equal groups of thirty. One group underwent neurolysis surgery alone, a second took methylcobalamin tablets at 0.5 milligrams three times daily, and the third received both interventions. Every patient also followed the same standardized rehabilitation program, and all groups completed two consecutive thirty-day treatment courses before their sixty-day assessments.

The headline result was striking. The combination group achieved a total effective rate of 86.67 percent, meaning most patients in that group showed clear grade improvements on the Carroll Upper Extremity Function Test, a validated zero-to-ninety-nine scale of hand and arm function. By contrast, the neurolysis-only group reached 50.00 percent and the methylcobalamin-only group 53.33 percent. Ten patients in the combination arm were classified as fully cured, compared with four in the surgery group and five in the vitamin group, and only four combination patients remained in the ineffective category.

Objective electrophysiological measurements told the same story. Using nerve conduction studies, the researchers tracked motor conduction velocity, sensory conduction velocity, compound muscle action potential amplitude, and latency. While all three groups improved significantly from baseline, the combination group posted the largest gains across every parameter. Motor conduction velocity, for example, rose from roughly 38 meters per second at baseline to nearly 50 meters per second after treatment in the combined arm, versus gains of about six meters per second in each monotherapy group. Faster conduction and higher amplitudes signal restored axonal integrity and improved myelination — the biological substrate of real-world function.

Those electrical improvements translated into movement. Active and passive joint range of motion, measured with a goniometer, improved in all groups but soared in the combination arm: active range of motion climbed from about 10.5 degrees to 42.2 degrees, and passive range of motion from about 24 degrees to nearly 63 degrees, roughly double the gains seen in either monotherapy group. Pain scores on the Global Pain Scale, which covers clinical symptoms, emotional state, daily activities, and pain intensity, fell in every group, but the combination group recorded the lowest post-treatment scores in all four domains.

Blood tests added a biochemical dimension to the findings. The researchers measured serum levels of three inflammatory mediators — nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) — using enzyme-linked immunosorbent assays on fasting blood samples. All three markers dropped after treatment in every group, but the combination group achieved the deepest suppression: NF-κB fell to 13.76 micrograms per liter, TNF-α to 16.45 micrograms per liter, and IL-6 to 6.37 picograms per milliliter, all significantly lower than in either monotherapy arm. The trial also reported markedly lower rates of limb numbness, joint stiffness, chronic pain, and limb atrophy among combination patients.

The logic behind the synergy is biologically coherent. Neurolysis is a mechanical fix: surgeons meticulously free the injured nerve from scar tissue, adhesions, or fibro-osseous tunnels, restoring its ability to glide and re-establishing blood supply. But surgery alone does little to correct the hostile biochemical environment inside the damaged nerve, where inflammatory cascades perpetuate injury and stall regeneration. Methylcobalamin works from the opposite direction. As the neuroactive form of vitamin B12, it supports axonal regeneration, promotes myelin synthesis, sustains neuronal survival, and — as prior research has shown — inhibits NF-κB signaling and the downstream cytokines that drive neuropathic pain. What it cannot do is physically decompress a nerve trapped in constrictive scar tissue.

The trial’s methodology deserves attention. It was prospective, randomized, and evaluator-blinded: an independent statistician generated the allocation sequence using permuted blocks, assignments were concealed in sequentially numbered opaque envelopes, and all outcome assessments — functional testing, nerve conduction studies, range-of-motion measurements, pain scoring, and laboratory analyses — were performed by assessors blinded to group allocation. Patients and surgeons could not be blinded to surgery, but the intention-to-treat analysis and blinded data handling reduce the risk of detection bias. The sample size was determined a priori by power analysis, and baseline characteristics, injury etiologies, and severity were balanced across the three groups.

The authors are candid about limitations. The study was single-center, so results may not generalize to other populations or surgical teams. The follow-up window was only sixty days, which captures early recovery but says nothing about long-term durability, symptom recurrence, or late complications. The patient cohort mixed several injury subtypes, and subtle variations in surgical technique and rehabilitation adherence are unavoidable in clinical practice. Larger, multicenter trials with follow-up of twelve months or longer, homogeneous injury groups, and optimized methylcobalamin dosing regimens will be needed before the combined approach can be considered a standard of care.

Even with those caveats, the findings carry real weight for a condition that has long lacked rigorous comparative evidence. Traumatic peripheral nerve injuries affect an estimated 13 to 23 people per 100,000 each year, and the resulting disability and chronic pain impose heavy personal and economic costs. If the synergy holds up in larger trials, the message for clinicians would be straightforward: mechanical decompression and pharmacological neuroprotection are not competing strategies but complementary halves of the same problem. Freeing the nerve gives it room to heal; feeding it methylcobalamin helps it actually regenerate. The combination, this trial suggests, is more than the sum of its parts.

Subject of Research: Combined neurolysis surgery and methylcobalamin therapy for peripheral nerve injury recovery

Article Title: Synergistic efficacy of combined neurolysis and methylcobalamin in peripheral nerve injury: a randomized clinical trial

Article References: Hu, X., & Li, Z. (2026). Synergistic efficacy of combined neurolysis and methylcobalamin in peripheral nerve injury: a randomized clinical trial. Frontiers in Integrative Neuroscience, 20, Article 1747898. https://doi.org/10.3389/fnint.2026.1747898

Image Credits: AI Generated

DOI: 10.3389/fnint.2026.1747898

Keywords: peripheral nerve injury, neurolysis, methylcobalamin, vitamin B12, nerve conduction, inflammation, NF-κB, TNF-alpha, IL-6, randomized clinical trial, neuropathic pain, nerve regeneration

The study, published in Frontiers in Clinical Diabetes and Healthcare, was conducted at two hospitals in Thai Binh province by a team from Thai Binh University of Medicine and Pharmacy and Hai Phong University of Medicine and Pharmacy. Between January 2024 and September 2025, the researchers recruited 400 adults with type 2 diabetes who had been taking metformin for at least six months. They deliberately excluded anyone whose vitamin B12 status could be compromised by other factors: patients with gastrectomy, ileal resection, Crohn disease, or celiac disease; those taking proton pump inhibitors, H2 receptor antagonists, or colchicine for more than a year; people with pernicious anemia or malignancies; strict vegetarians; and anyone already taking vitamin B12 supplements. The exclusions were designed to isolate the relationship between metformin itself and the vitamin’s availability in the bloodstream.

The numbers tell a layered story. Of the 400 participants, 103, or 25.75 percent, fell below the study-defined threshold of 300 picograms per milliliter. But only 29 of them, 7.25 percent, had absolute deficiency, defined as concentrations under 200 picograms per milliliter. The remaining 74, or 18.50 percent, occupied the marginal band between 200 and 300 picograms per milliliter, a zone whose clinical meaning is far less certain. The authors are careful to note that this serum-based definition includes marginal values and does not, by itself, establish functional deficiency, which would normally require additional biomarkers such as methylmalonic acid or homocysteine that were not measured in this study.

When the researchers examined which clinical characteristics tracked with low vitamin B12, two factors stood out in their exploratory adjusted analysis. Patients who had been taking metformin for more than five years had nearly twice the odds of falling below the threshold compared with those on shorter courses, with an adjusted odds ratio of 1.84 and a 95 percent confidence interval spanning 1.07 to 3.18. Anemia, defined by conventional World Health Organization hemoglobin cutoffs of under 130 grams per liter in men and under 120 grams per liter in women, carried even greater weight, with an adjusted odds ratio of 3.43 and a confidence interval of 1.62 to 7.23. Male sex and self-reported alcohol consumption showed higher proportions of low vitamin B12 in unadjusted comparisons, but neither retained statistical significance in the reported multivariable model.

The duration signal is consistent with what randomized and longitudinal evidence has long suggested. In a placebo-controlled trial published in BMJ in 2010, de Jager and colleagues observed a greater occurrence of biochemical vitamin B12 deficiency among insulin-treated patients with type 2 diabetes during long-term metformin treatment. The Diabetes Prevention Program Outcomes Study, a longitudinal analysis published in 2016, associated longer cumulative metformin exposure with low vitamin B12 status, though that population was originally recruited for diabetes prevention rather than treatment of established disease. The proposed mechanism centers on the gut: metformin appears to impair the calcium-dependent absorption of the vitamin B12-intrinsic factor complex in the ileum. In a small physiological study published in Diabetes Care in 2000, Bauman and colleagues demonstrated that calcium supplementation could reverse metformin-associated malabsorption, providing mechanistic support for the calcium-dependent hypothesis, though the authors of the new study emphasize that this does not constitute evidence for routine calcium supplementation in clinical practice.

The Vietnamese findings sit within a wider international landscape of prevalence estimates that vary with thresholds, supplementation, and sampling. Kim and colleagues reported vitamin B12 deficiency in 22.2 percent of 1,111 metformin-treated patients in Korea using the same threshold of under 300 picograms per milliliter. A multicenter Chinese study by Gao and colleagues evaluated definite and borderline categories separately and found associations with higher daily metformin doses but not with their selected duration categories. Within Vietnam itself, previous studies have reported prevalences of 18.6 percent in 156 patients by Huynh and colleagues and 22.1 percent among 145 patients at a southern tertiary hospital by Phan and colleagues, with the latter identifying adjusted associations with treatment duration, dose, and HbA1c. A study of elderly patients at Friendship Hospital by Vu and colleagues found that nearly 80 percent of participants reported vitamin B12 supplementation, making that population fundamentally incomparable with the supplement-free sample in the new study.

One of the most clinically consequential aspects of the study concerns the relationship between biochemical deficiency and symptoms that patients actually experience. Vitamin B12 deficiency can cause anemia and macrocytosis, an enlargement of red blood cells defined here as a mean corpuscular volume above 100 femtoliters. But macrocytosis was not statistically significant in either the univariable analysis or the reported multivariable model, and its adjusted confidence interval, spanning 0.79 to 79.37, is so wide that the point estimate cannot be reliably interpreted. More troubling is the neurological dimension: vitamin B12 deficiency can produce neuropathic symptoms that overlap with diabetic peripheral neuropathy, making it easy to attribute one condition’s damage to the other. Observational evidence on this overlap is inconsistent. Ahmed and colleagues did not identify a significant association between biochemical deficiency and peripheral neuropathy in their cross-sectional study, whereas Didangelos and colleagues reported improvement in several neurological measures after vitamin B12 supplementation in a randomized trial of selected metformin-treated patients with neuropathy. The authors caution that a low serum result and clinically manifest deficiency should not be treated as interchangeable outcomes.

The alcohol finding adds another layer of biological complexity. In unadjusted comparisons, participants reporting alcohol consumption had a low vitamin B12 proportion of 37.3 percent versus 22.7 percent among those not reporting consumption, with a crude odds ratio of 2.03. But the association attenuated in the adjusted model, and the binary self-reported measure did not characterize quantity, duration, or drinking pattern. Evidence from other populations suggests the relationship between alcohol and measured vitamin B12 status is more complex than a uniform decrease in serum concentration. Gibson and colleagues found that a controlled alcohol intervention reduced serum vitamin B12 in healthy male volunteers, while Fragasso and colleagues described alcohol-dependent patients with megaloblastic anemia who responded to vitamin B12 treatment despite normal or borderline serum concentrations. The authors cannot determine whether alcohol explains the higher unadjusted proportion in male participants or whether sex modifies an alcohol-related association, and no mediation or interaction analyses were presented.

The study’s limitations are substantial and the authors are unusually transparent about them. The cross-sectional design precludes temporal or causal conclusions, and hospital-based convenience sampling limits generalizability. All participants received metformin, so excess risk relative to nonuse could not be estimated. Baseline vitamin B12 values, dietary intake, methylmalonic acid, and homocysteine were unavailable. The reported adjusted model omitted diabetes duration and daily metformin dose, leaving potential residual confounding by treatment history. The macrocytosis estimate was highly imprecise, and no sensitivity analyses were performed to establish the stability of the adjusted estimates under alternative model specifications. The authors explicitly state that the adjusted findings remain exploratory and do not establish causality or model robustness, and that significance for one exposure and nonsignificance for another are not a test of the difference between their effects.

What practical guidance emerges from this evidence? The American Diabetes Association and the UK Medicines and Healthcare products Regulatory Agency already advise consideration of periodic vitamin B12 assessment during long-term metformin treatment, particularly in patients with risk factors or suggestive hematological or neurological findings. The new study’s five-year duration category can serve as a pragmatic prompt to prioritize review of vitamin B12 status, but the authors stress it is not a validated testing threshold and should not be a reason to defer testing earlier when deficiency is suspected. Patients with unexplained anemia or new neuropathic symptoms should be assessed regardless of treatment duration. Importantly, a low vitamin B12 result does not itself require discontinuation of metformin when the drug remains tolerated and otherwise appropriate. The study cannot specify an optimal testing interval or demonstrate a benefit of routine supplementation, and longitudinal research with detailed exposure measurement, functional biomarkers, and documented analytical plans is needed to clarify how metformin’s benefits and its biochemical side effects can be balanced over decades of treatment.

Subject of Research: Vitamin B12 deficiency prevalence and clinical factors among Vietnamese patients with type 2 diabetes receiving metformin therapy

Article Title: Prevalence and associated factors of vitamin B12 deficiency among Vietnamese patients with type 2 diabetes receiving metformin therapy: a cross-sectional study

Article References: Nguyen, T. K. D., Ke, T. L. A., Pham, V. L., Tran, X. T., & Vu, T. B. (2026). Prevalence and associated factors of vitamin B12 deficiency among Vietnamese patients with type 2 diabetes receiving metformin therapy: a cross-sectional study. Frontiers in Clinical Diabetes and Healthcare, 7, Article 1924740. https://doi.org/10.3389/fcdhc.2026.1924740

Image Credits: AI Generated

DOI: 10.3389/fcdhc.2026.1924740

Keywords: metformin, vitamin B12, type 2 diabetes, anemia, Vietnam, cross-sectional study, diabetic neuropathy, Prevalence, associated, factors, vitamin, deficiency

The research team, led by pediatric nephrologists at Fırat University Faculty of Medicine in Elazığ and a colleague at Çorlu Vega Hospital, followed forty children diagnosed with IgA vasculitis for at least six months. The investigators set out to evaluate a panel of laboratory parameters measured at initial admission: the neutrophil-to-lymphocyte ratio, a marker of systemic inflammation calculated from a routine blood count; serum osmolarity, a measure of the concentration of dissolved particles in the blood; homocysteine, an amino acid linked to vascular injury; vitamin B12; and antiphospholipid antibodies, immune proteins associated with abnormal clotting. Their goal was to determine whether any of these values tracked with renal involvement, the complication that matters most for long-term prognosis.

Immunoglobulin A vasculitis, historically known as Henoch-Schönlein purpura, is a multisystemic disease driven by the deposition of IgA-containing immune complexes in the walls of small blood vessels. Those deposits trigger inflammation that manifests as the characteristic palpable purpura, arthritis or arthralgia, gastrointestinal symptoms ranging from cramping to intussusception, and, in the most clinically consequential scenario, nephritis. According to figures cited in the study, nephritis develops in roughly 20 to 55 percent of children diagnosed with the condition. Because the renal disease can be silent in its early stages, clinicians rely on repeated urinalysis to catch blood or protein in the urine, and the search for additional early-warning markers has been a persistent theme in pediatric rheumatology and nephrology.

The cohort in the new study included twenty-three girls and seventeen boys, a female-to-male ratio of 1.35, with a mean age at diagnosis of approximately nine years. Renal involvement was identified in eleven patients, or 27.5 percent of the cohort. Eight of those children already had kidney involvement at the time of their first hospital presentation, while three developed it during the six-month follow-up period. This timing distinction proved critical to how the authors interpreted their results: in most cases, the laboratory measurements taken at admission were concurrent with kidney disease rather than preceding it, meaning the values reflect an association present at the same moment, not necessarily a prediction of what is to come.

Within that framework, three parameters stood out. Children with renal involvement had significantly higher neutrophil-to-lymphocyte ratios, higher serum urea concentrations, and higher serum osmolarity than children whose disease spared the kidneys. Vitamin B12 levels, by contrast, were significantly lower in the renal group. The differences reached statistical significance at a threshold of p less than 0.05. Serum potassium and homocysteine levels did not differ meaningfully between the two groups, and the presence of antiphospholipid antibodies showed no association with renal involvement, despite hypotheses that have linked these immune proteins to vascular complications in other inflammatory conditions.

The neutrophil-to-lymphocyte ratio deserves particular attention because it is one of the cheapest and most widely available markers in medicine. Neutrophils are the front-line cells of the innate immune system, summoned rapidly to sites of inflammation, while lymphocytes orchestrate adaptive immune responses and are often relatively depleted during acute inflammatory stress. When neutrophils rise or lymphocytes fall, the ratio climbs, offering a crude but reproducible index of systemic inflammatory burden. Elevated ratios have been reported across a wide range of inflammatory, infectious, and autoimmune diseases, and in IgA vasculitis they plausibly mirror the intensity of the immune activation that also drives IgA complex deposition in the glomeruli, the kidney’s microscopic filtering units. The new findings are consistent with that picture, showing that children whose blood already bore the signature of stronger inflammation were also the ones whose kidneys were affected.

The serum osmolarity finding adds a different dimension. Osmolarity reflects the combined concentration of sodium, glucose, urea, and other osmotically active solutes in the blood, and it is typically calculated from a standard chemistry panel rather than measured directly. Elevated osmolarity in children with renal involvement likely relates in part to higher urea concentrations, since urea is a direct contributor to the calculated value and also a marker of declining kidney clearance. In other words, the two elevated markers in the renal group may be partially intertwined, with osmolarity rising because the kidneys were already struggling to excrete nitrogenous waste. That interpretation reinforces the authors’ caution: the laboratory abnormalities may be consequences of early kidney injury as much as they are signals of it.

The lower vitamin B12 levels in the renal group are more enigmatic. Vitamin B12 is essential for red blood cell formation, neurological function, and the metabolism of homocysteine, which was itself not significantly different between the groups in this study. Why children with renal involvement would present with lower B12 is not established by the data, and the authors did not offer a definitive mechanism. Possible connections, such as differences in nutrition, the effects of inflammation on vitamin metabolism, or changes in renal handling of the vitamin, remain speculative. This is precisely the kind of signal that exploratory studies are designed to surface and that larger, more statistically powered investigations must interrogate before any clinical meaning is attached to it.

The authors are unusually direct about the limitations of their conclusions. Because renal involvement was already present in eight of the eleven affected children at the time the blood samples were drawn, the findings should be read as concurrent associations rather than validated predictors. A true predictive marker would need to be measured before kidney disease appears and shown to anticipate it in children who subsequently develop nephritis; only three patients in this cohort fit that temporal pattern, far too few to support a predictive claim. The sample size of forty is small, and the researchers themselves state that these exploratory biomarkers require confirmation in larger prospective cohorts. What the study does not do is displace the existing cornerstone of monitoring: routine urinalysis remains essential for every child with IgA vasculitis, since detecting blood or protein in the urine is still the most direct way to identify emerging nephritis.

Even with those caveats, the study contributes to a growing effort to complement urine testing with inexpensive blood-based markers available at the bedside on day one. The neutrophil-to-lymphocyte ratio, serum osmolarity, urea, and vitamin B12 all come from tests that virtually any hospital can perform within minutes, and a validated panel of such markers could, in principle, help clinicians stratify patients into closer follow-up schedules. Until replication studies confirm and extend these associations, the practical takeaway for clinicians is continuity rather than change: keep the six-month urinalysis vigil, and treat the new laboratory signals as hypotheses worth testing, not verdicts. The study received no external funding, was approved by the ethics committee of Fırat University Faculty of Medicine, and was published as open-access research, allowing clinicians and researchers worldwide to examine the data behind these early associations as the field works toward larger validation efforts.

Subject of Research: Biomarkers associated with renal involvement in childhood IgA vasculitis

Article Title: Clinical and laboratory parameters associated with renal involvement in childhood IgA vasculitis: a prospective cohort study

Article References: Esen Ağar, B., Çelikkol Yılmaz, I., Kara, A., & Gürgöze, M. K. (2026). Clinical and laboratory parameters associated with renal involvement in childhood IgA vasculitis: a prospective cohort study. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07809-z

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07809-z

Keywords: IgA vasculitis, Henoch-Schönlein purpura, pediatric nephrology, neutrophil-to-lymphocyte ratio, serum osmolarity, vitamin B12, renal involvement, IgA vasculitis nephritis, biomarkers, prospective cohort study, urinalysis, children's health

The study enrolled 1026 children and assessed their diets with a semi-quantitative food-frequency questionnaire, a tool that asks participants how often and in what quantities they consume a defined list of foods over a specified period. From those responses, the researchers estimated intake of individual B vitamins and derived dietary patterns using a statistical technique called reduced-rank regression. Unlike conventional pattern analysis, which simply clusters foods that tend to be eaten together, reduced-rank regression is directional: it searches for the combination of food groups that best explains a predefined intermediate variable, in this case B-vitamin intake. The resulting B-vitamin-rich dietary pattern was characterized by higher consumption of beans, dairy products, meats, grains, eggs, vegetables, and aquatic products, a mix that reads like a reasonably balanced plate rather than an exotic regimen.

To capture the opposite end of the nutritional spectrum, the team constructed a B-Vitamin Deficiency Index, or BVDI, which quantifies cumulative inadequacy across eight B vitamins relative to the Chinese Dietary Reference Intakes. Rather than flagging a single shortfall, the index tallies how many B vitamins a child falls short on, offering a composite picture of nutritional risk. Bone mineral density was measured at the forearm using dual-energy X-ray absorptiometry, the same low-dose imaging technique used to screen adults for osteoporosis. Forearm measurement is a practical choice in pediatric field studies: it is quick, involves minimal radiation, and correlates with skeletal status during growth.

The statistical architecture of the analysis was deliberately cautious. The researchers used multivariable logistic regression to estimate the odds of low bone mineral density across quartiles of intake, adjusting for potential confounders, and they employed restricted cubic splines to model dose-response relationships without forcing them into straight lines. When the results came in, three vitamins stood out. Children in the highest quartile of riboflavin, vitamin B2, had 57 percent lower odds of low bone mineral density than those in the lowest quartile, with an odds ratio of 0.43 and a 95 percent confidence interval of 0.25 to 0.74. Higher intakes of folate, vitamin B9, and cobalamin, vitamin B12, told a similar story, with odds ratios of 0.50 and 0.46 respectively, both statistically significant at conventional thresholds.

The B-vitamin-rich dietary pattern itself showed an inverse but borderline association with low bone mineral density, with an odds ratio of 0.61 and a confidence interval of 0.36 to 1.02 that just grazed the null value of 1.0, yielding a p-value of 0.060. That near-miss is a familiar frustration in nutritional epidemiology, where confidence intervals frequently hover at the edge of significance. It suggests a trend consistent with the individual-vitamin findings but leaves open the possibility that the pattern, as a composite exposure, carries less signal than its components, or that the study size limits the precision of the estimate.

The most striking result concerned the deficiency index. Children in the highest quartile of the BVDI, meaning they had the greatest cumulative inadequacy across the eight B vitamins, had 72 percent higher odds of low bone mineral density than children in the lowest quartile, with an odds ratio of 1.72 and a confidence interval of 1.02 to 2.92. In other words, the more B-vitamin shortfalls a child accumulated, the greater the apparent risk to skeletal density. This graded relationship across the index is notable because it treats B-vitamin status as a spectrum rather than a binary deficiency, reflecting the reality that marginal inadequacy, not just frank deficiency, may matter during the years when the skeleton is being built.

Why would B vitamins influence bone at all? The biological plausibility rests on several mechanisms, some of which are supported by experimental work cited in the study. Riboflavin functions as a cofactor in energy metabolism and has antioxidant properties; animal research has shown that riboflavin deficiency reduces bone mineral density by compromising osteoblast function, the activity of the cells that build bone matrix. Folate and vitamin B12 participate in one-carbon metabolism, the biochemical pathway that keeps levels of homocysteine, an amino acid, in check. Elevated homocysteine has been identified as a pathological biomarker for bone disease, implicated in disrupting collagen cross-linking and stimulating bone resorption. Genetic evidence adds another layer: a well-known study found that a polymorphism in the methylenetetrahydrofolate reductase gene interacts with riboflavin intake to influence bone mineral density, hinting that B-vitamin status can modulate genetically determined skeletal risk.

The pediatric context amplifies the stakes. Peak bone mass, the maximum bone strength a person achieves, is largely laid down during childhood and adolescence, and deficits during this window can persist for decades, raising lifetime fracture and osteoporosis risk. Most research on B vitamins and bone has focused on older adults, where trials have examined supplementation effects on density and fracture. Evidence in children has been thinner, which is what makes this study’s population approach noteworthy. It also aligns with related work: meta-analyses of randomized trials have found that dairy supplementation improves bone health indices in children aged three to eighteen, and a two-year randomized trial in adults with lower vitamin B12 status showed that low-dose B-vitamin supplementation benefited bone mineral density, suggesting the mechanism is not confined to any one life stage.

The authors are careful about what their design can and cannot show. As a cross-sectional study, it captures diet and bone density at a single point in time, so it cannot establish that B-vitamin intake causes stronger bones. Children who eat more B-vitamin-rich foods may differ in many ways from those who do not, including in overall diet quality, physical activity, socioeconomic circumstances, and body composition, and although the analysis adjusted for measured confounders, residual confounding remains possible in any observational study. Reverse causation is less of a concern for dietary exposures than for, say, physical activity, but the temporal ordering of diet and bone status is still unresolved. The findings are best read as a hypothesis-generating signal that B-vitamin nutritional status may be related to skeletal health indicators in childhood, a framing the authors adopt explicitly.

Even with those caveats, the study adds a practical dimension to pediatric nutrition. The foods that defined the B-vitamin-rich pattern, including beans, dairy, meats, grains, eggs, vegetables, and aquatic products, are ordinary components of a varied diet, and the analysis suggests that the collective contribution of these foods to B-vitamin status may matter for growing skeletons. If future longitudinal studies and randomized trials confirm the association, B vitamins could join the roster of nutrients that pediatricians and parents consider when planning diets for school-aged children, alongside calcium and vitamin D. For now, the message is measured: three specific B vitamins and a composite deficiency index are associated with bone mineral density in Chinese children aged nine to twelve, and the cumulative burden of inadequacy appears to matter more than any single shortfall. In the architecture of the growing skeleton, it seems, the supporting cast of nutrients may deserve more attention than it has traditionally received.

Subject of Research: Associations between B-vitamin intake, B-vitamin-rich dietary patterns, and bone mineral density in school-aged children

Article Title: The role of B-vitamin intake, B-vitamin-rich dietary patterns, the B-vitamin deficiency index in bone mineral density among school-aged children

Article References: Tan, L., Zhang, Y., Cui, N., Huang, S., Weng, S., Bao, M., Jiang, Y., Huang, M., & Yang, X. (2026). The role of B-vitamin intake, B-vitamin-rich dietary patterns, the B-vitamin deficiency index in bone mineral density among school-aged children. Pediatric Research. https://doi.org/10.1038/s41390-026-05403-8

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05403-8

Keywords: B vitamins, bone mineral density, children, riboflavin, folate, vitamin B12, dietary patterns, B-Vitamin Deficiency Index, pediatric nutrition, dual-energy X-ray absorptiometry, homocysteine, osteoporosis

The research centers on a class of nanomaterials known as carbon dots, nanoscale carbon-based particles that have attracted widespread attention for their strong fluorescence, low toxicity, ease of synthesis, and chemical tunability. In this work, the team prepared boron- and nitrogen-co-doped carbon dots, abbreviated B,N-CDs, using a one-step hydrothermal process starting from 3-aminophenylboronic acid and p-hydroxybenzaldehyde. The co-doping with boron and nitrogen is not decorative; heteroatom doping modifies the electronic structure and surface chemistry of carbon dots, and in this case it produced water-dispersible nanoparticles averaging about one nanometer in diameter that emit a bright blue fluorescence when excited by ultraviolet light.

The optical performance of the probe is central to its usefulness. Under 390 nm excitation, the B,N-CDs showed their strongest fluorescence emission at 475 nm, with a quantum yield of 18.15 percent, a figure that indicates a substantial fraction of absorbed photons are converted into emitted light. When vitamin B12 was introduced, the blue glow dimmed markedly. The probe displayed a linear fluorescence response across vitamin B12 concentrations from 0 to 100 micromolar, with a detection limit of 0.02 micromolar, a sensitivity level that places the method comfortably within the range needed for food analysis applications.

Selectivity is where many fluorescent probes falter, since real food samples contain a crowded mixture of molecules that can interfere with a signal. The Liaocheng team tested the probe against other B vitamins, amino acids, glucose, and a panel of common small molecules. Vitamin B12 produced pronounced quenching of the fluorescence, while the other tested substances caused little comparable response. That discrimination matters because a sensor that dims in response to anything would be useless in a food matrix, whereas one that responds specifically to the target analyte can deliver a meaningful reading even in chemically complex surroundings.

Understanding why the fluorescence fades was a substantial part of the study. The researchers assembled evidence from fluorescence-lifetime measurements, UV-visible absorption spectroscopy, Raman spectroscopy, FT-IR, X-ray photoelectron spectroscopy, particle-size analysis, and surface-charge measurements. The fluorescence lifetime of the carbon dots remained unchanged in the presence of vitamin B12, while Stern-Volmer plots recorded at different temperatures showed temperature-dependent behavior. Together, these observations support a static quenching mechanism: vitamin B12 associates with the carbon dots to form a non-luminescent complex in the ground state, effectively switching off the emission of the dots it binds. Zeta potential and dynamic light scattering measurements of the dots, the vitamin, and their combined system further corroborated this interaction, explaining why the blue fluorescence decreases predictably as vitamin B12 concentration rises.

What distinguishes this work from many fluorescence-probe studies is the deliberate translation of the liquid-phase assay into physical formats that a non-specialist could conceivably use. The researchers impregnated filter paper with the B,N-CDs to create test strips, and they designed a cotton-swab device that carries the fluorescent probe to a sensing region during use. Under 365 nm ultraviolet light, both formats became progressively darker as vitamin B12 concentration increased, turning the analytical signal into something visible to the eye rather than something requiring a spectrometer.

The paper strip format was quantified through image-based analysis of the green-to-blue intensity ratio extracted from photographs of the strips. This ratio showed a strong linear relationship with vitamin B12 concentration from 0 to 80 micromolar, with a coefficient of determination of 0.9927. In practical terms, that means a camera image of an illuminated strip can serve as the measurement instrument, an approach that aligns naturally with the ubiquity of smartphone cameras and opens a path toward quantitative readings without dedicated laboratory equipment.

The cotton-swab sensor represents a different kind of design ambition. Rather than merely displaying a signal, the swab was conceived to combine sample collection, transfer, mixing, and signal readout within a single disposable device. Once a suitable sample is available, the sensing step can be completed rapidly, collapsing several laboratory operations into one handheld object. Both the strips and the swabs retained useful fluorescence and vitamin B12 sensing performance for at least 20 days under the storage conditions evaluated, an important consideration for any sensor intended to be distributed, stored, and used outside a controlled laboratory environment.

To check whether the method could survive contact with real food, the researchers applied it to egg-yolk and goat-liver-powder samples, both genuine dietary sources of vitamin B12. They compared their quantitative measurements against high-performance liquid chromatography, the established reference technique. In spiked recovery experiments, recoveries ranged from 97.09 percent to 101.22 percent, and the measured vitamin B12 concentrations closely matched the HPLC results. For an alternative analytical method, agreement with a gold-standard technique at that level of accuracy is the key benchmark, and it supports the credibility of the carbon-dot approach in the food matrices studied.

The authors are candid about what remains before the technology can be considered field-ready. The current real-food workflow still involves laboratory sample pretreatment before measurement, so simplifying that step will be essential for truly portable testing. They also outline practical next steps, including replacing the laboratory ultraviolet lamp with a compact battery-powered UV-LED and adding smartphone-based image analysis for automated quantification. Even with those caveats, the study demonstrates that carbon-dot fluorescence can be adapted into visually readable portable sensors without sacrificing the sensitivity or selectivity that make the underlying chemistry useful, and it offers a template for how other analytes might be moved onto paper strips and swabs in the future.

Subject of Research: Fluorescence-based portable detection of vitamin B12 using boron- and nitrogen-co-doped carbon dots in food samples

Article Title: A blue glow for vitamin B12: carbon dots bring testing to paper strips and swabs

Article References: A blue glow for vitamin B12: carbon dots bring testing to paper strips and swabs. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: vitamin B12, carbon dots, fluorescence quenching, biosensors, food analysis, paper strips, cotton swab sensor, point-of-care testing, nanomaterials, static quenching, HPLC validation, Liaocheng University