folic acid + vitamin B6 + vitamin B12 + primorine (Folmor)

Vitamin B12 deficiency, restless legs syndrome and poor sleep quality in adolescents: A cross-sectional study.

Boztepe Kubra K, Ozkan Nurten Zarif NZ, Gol Nesibe Kubra NK, Pirgon Ozgur O

Although the role of dopaminergic dysfunction and iron metabolism in the pathophysiology of restless legs syndrome (RLS) has been widely investigated, the potential association between vitamin B12 status and RLS remains insufficiently explored. In particular, data in pediatric and adolescent populations are limited and inconsistent. Moreover, while sleep disturbance is a well-recognized feature of RLS, the combined relationship between vitamin B12 levels, RLS, and sleep quality has not been adequately evaluated in adolescents. Therefore, the present study aimed to investigate the association between vitamin B12 levels and the presence of RLS, and to assess sleep quality in adolescents with and without RLS. Dysfunction of the dopaminergic system is known to play a role in the pathophysiology of patients with restless legs syndrome (RLS). Vitamin B12 functions as a cofactor in pathways involved in dopamine synthesis. This study was conducted to investigate the association between vitamin B12 levels and restless legs syndrome (RLS) and to evaluate the relationship between RLS and sleep quality. The study was conducted with 146 pediatric patients aged 10-16 years who applied to pediatric outpatient clinics. All patients were evaluated for RLS according to the diagnostic criteria established by the International RLS Study Group (IRLSSG). Patients with symptoms of RLS were scored using the disease symptom severity scale defined by the same group, and comparisons were made between the groups. To assess sleep quality, the Pittsburgh Sleep Quality Index (PSQI) questionnaire was administered to all patients, and the results were recorded and compared across all groups. There were no statistically significant differences in hemoglobin, hematocrit, ferritin, folic acid, or glucose levels. Serum vitamin B12 levels were found to be significantly lower in patients with RLS compared to those without the syndrome. Our total PSQI scores were statistically higher in the RLS group than in the non-restless legs syndrome group. Patients were divided into three groups according to their vitamin B12 levels: "deficient," "borderline," and "sufficient." When these three groups were compared in terms of the frequency of restless legs syndrome, its prevalence was statistically higher in the group with insufficient vitamin B12 levels. Conclusion: Our findings suggest an association between lower vitamin B12 levels and the presence of RLS in adolescents. However, due to the cross-sectional design of the study, causality cannot be established and further prospective studies are needed to confirm these findings. In addition, consistent with the literature, sleep quality was found to be impaired in patients with RLS in our study. What is known • RLS is associated with sleep disturbance and reduced quality of life • Evidence on the relationship between vitamin B12 and RLS is limited, especially in adolescents What is new • Lower vitamin B12 levels were associated with a higher frequency of RLS in unadjusted analyses • Vitamin B12 status may be related to sleep quality in this population.

Methodological Considerations in Assessing Metformin-Associated Vitamin B12 Deficiency.

Halog Evangeline A EA, Mangaoang Ray L RL, Aban Jomar L JL

Vitamin B12-mediated microglial immunometabolic reprogramming: A novel mechanistic insight into diabetes-associated cognitive impairment.

Zhang Xin X, Li Jing J, An Yu Y, Zheng Jie J et al.

Diabetes-associated cognitive impairment (DCI) is an increasingly recognized neurological complication of type 2 diabetes mellitus characterized by chronic neuroinflammation and microglial immunometabolic dysregulation. Vitamin B12 (VB12) deficiency, which is highly prevalent in patients with diabetes, has been strongly associated with cognitive decline, hippocampal atrophy, and white matter injury. Emerging evidence suggests that VB12 plays a critical role in maintaining one‑carbon metabolism, mitochondrial function, and redox homeostasis. Mechanistically, VB12 deficiency promotes homocysteine accumulation, disrupts the S-adenosylmethionine/S-adenosylhomocysteine balance, impairs mitochondrial oxidative phosphorylation, and enhances oxidative stress, thereby driving pro-inflammatory microglial activation and sustained neuroinflammation. In addition, gut microbiota dysbiosis, particularly reduced abundance of Akkermansia muciniphila and other VB12-producing bacteria, may further impair VB12 bioavailability and aggravate neuroinflammation through the gut-brain axis. This review summarizes current evidence linking VB12 deficiency to microglial immunometabolic remodeling in DCI and discusses the therapeutic potential of targeting VB12 metabolism and gut microbial ecology for preventing diabetes-related cognitive decline.

Content of Vitamin D2 in Alternative Biological and Nutritional Sources and Its Effectiveness as Compared to Vitamin D3-A Narrative Review.

Bieg Filip F, Galanty Agnieszka A, Arancibia-Ávila Patricia P, Gorinstein Shela S et al.

Background/Objectives: Interest in alternative, non-animal sources of vitamin D has increased due to the global prevalence of its deficiency and the growing demand for plant-based dietary options. Mushrooms and algae have emerged as potential sustainable sources of vitamin D2 and, in selected cases, vitamin D3 following ultraviolet (UV) exposure. However, the comparative bioavailability and clinical effectiveness of vitamin D2 relative to vitamin D3 remain controversial. This review aims to evaluate the content of vitamin D2 in mushrooms and algae, the impact of UV irradiation on its synthesis, and the effectiveness of vitamin D2 supplementation compared with vitamin D3 in humans. Methods: PubMed, ScienceDirect, and Google Scholar were searched (1996-2026). Only human intervention studies were included when assessing clinical efficacy. Data on natural sources and pharmaceutical formulations were analyzed. Results: UV irradiation markedly increases vitamin D2 content in mushrooms, as compared to cultivated products. Algal vitamin D content varies, depending on species and UV exposure, with no robust clinical trials confirming improvement of serum 25(OH)D after algal supplementation. Across multiple randomized controlled trials, vitamin D2 consistently increased circulating 25(OH)D2 but frequently reduced 25(OH)D3 and demonstrated lower efficacy in raising total 25(OH)D compared with vitamin D3, as confirmed by a recent meta-analysis. Conclusions: Although UV-enhanced mushrooms represent a quantifiable dietary source of vitamin D2, clinical evidence consistently indicates lower efficacy of vitamin D2 compared with vitamin D3. Algae cannot currently be considered a validated source of vitamin D for improving human vitamin D status. Further mechanistic and long-term clinical studies are required.