Vitamin B12 is associated negatively with anemia in older Chinese adults with a low dietary diversity level: evidence from the Healthy Ageing and Biomarkers Cohort Study (HABCS).

OBJECTIVE: The associations between plasma vitamin B12 level and anemia under different dietary patterns in elderly Chinese people are poorly understood. We aimed to examine the associations between plasma vitamin B12 levels and anemia under different dietary patterns in adults aged 65 years and older in nine longevity areas in China. METHODS: A total of 2405 older adults completed a food frequency questionnaire at the same time as a face-to-face interview. The dietary diversity score (DDS) was assessed based on the food frequency questionnaire, with the low DDS group referring to participants with a DDS score ≤ 4 points. Vitamin B12 levels were divided into two groups of high (>295 pg/mL) and low (≤ 295 pg/mL) with the median used as the cut-off point. Sub-analyses were also performed on older adults divided into tertiles of vitamin B12 levels: low (< 277 pg/mL), medium (277-375 pg/mL) and high (> 375 pg/mL) to study the association of these levels with anemia. RESULTS: Six hundred ninety-five (28.89%) of these people were diagnosed with anemia and had a mean age of 89.3 years. Higher vitamin B12 levels were associated with a decreased risk of anemia (multi-adjusted OR, 0.59, [95% CI, 0.45 ~ 0.77] P < 0.001) in older adults with a low DDS, whereas no significant association between vitamin B12 levels and anemia was found in older adults with a high DDS in a full-model after adjustment for various confounding factors (multi-adjusted OR, 0.88, [95% CI, 0.65 ~ 1.19], P = 0.41). CONCLUSION: The relationship between vitamin B12 levels and the prevalence of anemia was significant only when the level of dietary diversity in the older adults was relatively low. The dietary structure of the population should be taken into consideration in combination in order to effectively improve anemia status by supplementing vitamin B12.

A micronutrient supplement modulates homocysteine levels regardless of vitamin B biostatus in elderly subjects.

Elevated homocysteine (Hcy) levels (≥15 µmol/L) in the elderly are frequently associated with a higher risk of cardiovascular disease and cognitive decline. Several studies have already shown an Hcy-lowering effect of B vitamin supplementation in cohorts deficient in these nutrients. The aim of this randomized, double-blinded 12-week intervention study was to investigate whether Hcy levels in healthy elderly subjects (75.4±4.5 years, n=133) could be lowered with a micronutrient supplement (i.e., 400 µg folic acid, 100 µg cobalamin). Difference in mean initial Hcy levels between intervention (17.6±7.1 µmol/L, n=65) and placebo group (18.9±6.1 µmol/L, n=68) was not significant. The prevalence of cobalamin and folate deficiency in the total study population was low: 27% had serum-cobalamin levels ≤150 pmol/L, 12% holo-transcobalamin (Holo-TC) levels ≤50 pmol/L, 13% low cobalamin status using the aggregated cobalamin marker 4cB12 and 10% red blood cell (RBC) folate ≤570 nmol/L. Nevertheless, the treated subjects still showed improved cobalamin and folate biostatus (serum cobalamin Δt12-t0: 63±48 pmol/L; Holo-TC Δt12-t0: 17±19 pmol/L; RBC folate Δt12-t0: 326±253 nmol/L) and Hcy levels (Δt12-t0: -3.6±5.7 µmol/L). The effects were statistically significant compared to the placebo group with p=0.005 (serum cobalamin), p=0.021 (Holo-TC), p=0.014 (RBC-folate) and p<0.001 (Hcy). The Hcy-lowering effect was dependent on the initial Hcy levels (p<0.001). Our findings suggest that elevated Hcy levels in elderly subjects can be lowered regardless of the initial cobalamin and folate biostatus.

Vitamin B12 and Folate Status in Pregnant Females and Their Infants in Norway: Secondary Analysis from the Mommy's Food Study.

BACKGROUND: Vitamin B12 and folate are essential micronutrients important for normal infant growth and development. OBJECTIVES: The aims were to describe vitamin B12 and folate status in pregnant females and their infants according to commonly used status cutoffs and examine the associations between maternal status, maternal supplement use, and breastfeeding and infant status. METHODS: Pregnant females were recruited at 18 wk gestation in Bergen, Norway. Maternal vitamin B12 and folate status were measured at gestational weeks 18 (n = 136) and 36 (n = 116), and infant status was measured at ages 3 (n = 73) and 6 (n = 74) mo. RESULTS: At gestational weeks 18 and 36, respectively, 4.4% and 2.6% of the mothers had plasma cobalamin concentrations <148 pmol/L, 0.7% and 6.9% had methylmalonic acid (MMA) concentrations >0.26 µmol/L, and 3.7% and 30% had folate concentrations <10 nmol/L. None of the females had total homocysteine (t-Hcy) concentrations >13 µmol/L or 3 combined indicator of vitamin B12 (cB12) < -0.5. At 3 and 6 mo, respectively, 4.1% and 5.4% of the infants had cobalamin concentrations <148 pmol/L, 63% and 74% had t-Hcy concentrations >6.5 µmol/L, 59% and 66% had MMA concentrations >0.26 µmol/L, and 47% and 60% had cB12 > -0.5. None of the infants had folate concentrations <10 nmol/L. Several of the vitamin B12 biomarkers in infants were associated with maternal vitamin B12 status during pregnancy. Breastfed infants had lower vitamin B12 status (as indicated by plasma cobalamin, t-Hcy, and cB12) than nonbreastfed infants at both 3 and 6 mo. Use of supplements during pregnancy was associated with better vitamin B12 status among infants at 3 and 6 mo, as indicated by infants' cobalamin and t-Hcy concentrations. CONCLUSIONS: Subclinical vitamin B12 deficiency among infants was common and associated with maternal vitamin B12 status during pregnancy and breastfeeding. Among the mothers, an increase in biochemical folate deficiency was discovered toward the end of gestation. Further studies are needed to investigate clinical consequences. This trial was registered at clinicaltrials.gov as NCT02610959.

A Study on Vitamin B12 Levels in Hypothyroid Patients Presenting to a Tertiary Care Teaching Hospital.

INTRODUCTION: Prevalence of vitamin B12 deficiency is occasionally found to be coexisting in patients with hypothyroidism causing persistence of symptoms concomitant to both diseases even on adequate thyroxine supplementation. MATERIALS: A single-centric non-interventional cross sectional study was carried over a period of 1 year. 100 hypothyroid patients were evaluated for prevalence of anemia, and investigated for the etiology. Serum Vitamin B12 was obtained and an association was studied between Vitamin B12 and anti TPO and anti Thyroglobulin antibodies. Here, vitamin B12 deficiency was defined as <160 pg/mL. RESULT: Among 100 hypothyroid patients, 31% were males and 69% were females. The mean age of patients was 36.09±12.864 years. 68% patients were found to be Vitamin B12 deficient, and 73.5% of this deficient population were females. 78.6% patients with raised Anti TPO antibodies had vitamin B12 deficiency (p-value = 0.01), while 78% patients with raised Anti Thyroglobulin antibodies were vitamin B12 deficient (p-value = 0.07). The Pearson correlation coefficient (r) was -0.302 (p = 0.002) and -0.253 (p = 0.011) between Vitamin B12 anti anti TPO and anti Thyroglobulin antibodies respectively, thus showing a negative correlation between both. CONCLUSION: Thyroid hormones affect erythropoiesis, thus causing anemia in a deficient condition. In iodine sufficient areas, most common cause of hypothyroidism is autoimmune, predisposing individuals to other autoimmune diseases, one being pernicious anemia. In the studied anemic hypothyroid population, Vitamin B12 deficiency was found correlated with raised levels of serum anti-TPO and anti-Thyroglobulin antibodies. Supplementation of B12 may alleviate hypothyroid symptoms, thus making itself a novel addition in the routine hypothyroid prescription. References Aon M, Taha S, Mahfouz K, et al. Vitamin B12 (cobalamin) deficiency in overt and subclinical primary hypothyroidism. Clin Med Insights Endocrinol Diabetes 2022;15:11795514221086634. Ness-Abramof R, Nabriski DA, Shapiro MS, et al. Prevalence and evaluation of B12 deficiency in patients with autoimmune thyroid disease. Am J Med Sci;332(3):119-122.

Determinants of vitamin B12 deficiency in patients with type-2 diabetes mellitus - A primary-care retrospective cohort study.

BACKGROUND: Like many developed nations, the prevalence of both older people and type-2 diabetes mellitus (T2DM) in Singapore is rising. This demographic shift predisposes the population to greater risks of both frailty and its complications that can be further aggravated by vitamin B12 deficiency -a highly prevalent associated variable that is potentially modifiable. Indeed, B12 deficiency adversely impacts the neuro-cognitive, haematological, and even the immune systems; jeopardizing our aspirations for successful aging. Despite this, many patients with T2DM in primary care remain unscreened due to a lack of clear guidelines for regular B12 screening. We therefore investigated the determinants of B12 deficiency in community-dwelling patients with T2DM, with the aim of profiling patients most in need of B12-deficiency screening. METHODS: B12 deficiency was evaluated using a retrospective cross-sectional cohort of 592 primary-care patients with T2DM, recruited from 2008 to 2011 from a Polyclinic in Singapore. RESULTS: B12 deficiency (serum B12 < 150 pmol/L) was present in 164 (27.7%) patients and was associated with a higher "metformin daily dose" (OR = 2.79; 95% CI, 2.22-3.48, P < 0.001); "age ≥ 80 years" (OR = 2.86; 95% CI, 1.31-6.25, P = 0.008); "vegetarianism" (OR = 21.61; 95% CI, 4.47-104.44, P < 0.001); and "folate deficiency" (OR = 2.04; 95% CI, 1.27-3.28, P = 0.003). Conversely, "Prescribed B12 supplementation" was associated with a lower odds of B12 deficiency (OR = 0.37; 95% CI: 0.22-0.61, P < 0.001). The area under the receiver operating characteristic curve was 0.803 (95% CI: 0.765-0.842). "Metformin daily dose" correlated interchangeably with "Metformin 1-year cumulative dose" (r = 0.960; P < 0.01), and also associated linearly with "duration of diabetes" (B = 0.113, P < 0.0001). Independent of the duration of T2DM, 29.3% of the B12-deficient patients needed > 1 screening test before the detection of B12 deficiency. CONCLUSIONS: Primary-care screening for B12 deficiency should be part of the annual laboratory review of patients with T2DM regardless of the duration of T2DM -especially when they are prescribed ≥ 1.5 g/day of metformin; ≥ 80 years old; vegetarian; and not prescribed B12 supplementation. Concurrent evaluation for associated folate (vitamin B9) deficiency is essential when addressing T2DM-associated B12 deficiencies. Current "Metformin daily dose" is an accurate proxy of both cumulative metformin exposure and duration of T2DM.

The Continued Need for the Routine Assessment of Folate Status.

OBJECTIVE: The Choosing Wisely initiative recommended cessation of folate measurement, suggesting folate supplementation in macrocytic anemia. This study reviewed the need for continued blood folate testing at a large SafetyNet county teaching hospital. METHODS: Red blood cell (RBC) folate, vitamin B12, iron, ferritin, and hemoglobin results were obtained for utilization review. RESULTS: Of the 593 RBC folate results, 69 (11.7%) were deficient and 30 (5%) had high values. Collectively, 369 (73.9%) had normal vitamin B12 levels, 342 (70%) had low hemoglobin, 184 (62.5) had normal and 57 (19.4%) had low ferritin, 122 (38.2%) had normal and 188 (59%) had low iron levels. A total of 41 (12%) had normal folate, low ferritin, low hemoglobin, and low iron, suggestive of iron deficiency anemia. There were 11 patients who exhibited low folate, low or normal ferritin, low hemoglobin, and low iron levels, suggesting combined folate and iron deficiency anemias. CONCLUSION: This study highlights the need for institutions to assess the applicability of national recommendations to their local population.

Metformin-Induced Vitamin B12 Deficiency among Type 2 Diabetes Mellitus' Patients: A Systematic Review.

BACKGROUND: Type 2 diabetes mellitus is one of the most globally common chronic diseases. Metformin is the most popular prescribed medication for the treatment of diabetes. Studies suggest that metformin is associated with vitamin B12 deficiency, which may impart adverse health complications. OBJECTIVE: This review screens the literature to clarify the effect of metformin on vitamin B12 deficiency among type 2 diabetes mellitus patients. METHODS: Google Scholar, PubMed, Research Gate, and Semantic Scholar, were searched for the association between metformin intake and vitamin B12 deficiency in type 2 diabetes mellitus patients using relevant keywords and their combinations. Selected studies were those conducted on patients taking metformin with no vitamin B12 supplement. Nineteen studies (fifteen observational studies and four randomized controlled trials) met the inclusion criteria. These studies were assessed for design, setting, study population, and overall quality. RESULTS: There is a positive correlation between metformin intake and vitamin B12 deficiency. This has been accompanied by increased homocysteine and decreased folate levels. Despite the refuting of the findings, most studies showed that higher doses of metformin were strongly associated with lower vitamin B12 levels, while the duration of treatment was not. CONCLUSION: Regular measurement of vitamin B12 levels during long-term metformin treatment is recommended. A clear policy should be in place to illuminate the importance of this screening in preventing vitamin B12 deficiency complications. Taking therapeutic supplements or injections of vitamin B12 along with a vitamin B12-rich diet may decrease the incidence of its deficiency in diabetic patients taking metformin.

Diagnosis, Treatment and Prevention of Nutritional Anemia in Children: Recommendations of the Joint Committee of Pediatric Hematology-Oncology Chapter and Pediatric and Adolescent Nutrition Society of the Indian Academy of Pediatrics.

JUSTIFICATION: Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. OBJECTIVE: To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. PROCESS: These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. RECOMMENDATIONS: We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.

Fylkesforskjeller i utredning og behandling av vitamin B12-mangel.

BACKGROUND: Severe vitamin B12 (cobalamin) deficiency is rare, but international reports show that up to 26 % of the general population may have subclinical vitamin B12 deficiency. The prevalence of vitamin B12 deficiency has not been investigated in Norway. Since 2017, treatment with vitamin B12 tablets has represented an alternative to traditional treatment with intramuscular injections in Norway. When we studied the transition from injection to tablet treatment, we discovered an unexpected difference in the counties' use of vitamin B12 supplements, which we wished to investigate in more detail. MATERIAL AND METHOD: Data on the dispensing of vitamin B12 supplements from pharmacies in 2020, broken down by the patients' county of residence, were retrieved from the Norwegian Prescription Database. The Norwegian Health Economics Administration (Helfo) provided figures on the number of reimbursed vitamin B12-related laboratory tests in 2020, classified by patients' municipality of residence. RESULTS: In 2020, the sale of vitamin B12 supplements on prescription in Norway amounted to 12 defined daily doses (DDD) per inhabitant and varied from 7 to 15 between the counties. The number of laboratory analyses that were performed varied by county from 26 to 46 per 100 inhabitants for total vitamin B12, and from 21 to 37 for folate. The number of analyses varied correspondingly from 1 to 12 per 100 inhabitants for homocysteine, from 1 to 13 for methylmalonic acid and from 0.01 to 8.13 for active vitamin B12. INTERPRETATION: Our study showed large intercounty differences in the consumption of vitamin B12 supplements. These differences may have a number of explanations. Variations in the number of vitamin B12-related laboratory analyses requisitioned may indicate that doctors' assessment and diagnosis of vitamin B12 deficiency could be a contributory factor.

Intake of Vitamin B12 and Folate and Biomarkers of Nutrient Status of Women within Two Years Postpartum.

Background: Little is known about variation in vitamin B12 and folate status among Chinese women 2 years postpartum. This study assessed intake of vitamin B12 and folate and biomarkers of nutrient status among Chinese women postpartum. Methods: Demographic information, multi-/single-nutrient supplementation, dietary data, serum vitamin B12 and serum folate were assessed in 982 women within 2 years postpartum, using ten investigation sites in Zhejiang Province from the National Nutritional Study 2016−2017, which is a nationally representative cross-sectional study, to form a representative provincial sample of Zhejiang Province. The dietary diversity score (DDS) was used for assessing the dietary pattern. Results: Vitamin B12 increased slightly at the early stage of postpartum and then dropped over time. Serum folate level elevated with postpartum time. The median serum vitamin B12 concentration was 494.59 (373.21−650.20) pg/mL, and folate was 7.58 (5.02−10.34) ng/mL. Correspondingly, vitamin B12 levels suggesting marginal deficiency (200−300 pg/mL) and deficiency (<200 pg/mL) resulted as 9.27% and 3.26%, respectively, and folate level suggesting deficiency (<3 ng/mL) was 9.16%. Multi-/single-nutrient supplementation during pregnancy was associated with log-transformed serum vitamin B12 and folate level after adjusting for potential confounders (vitamin B12: ß (SE) = 0.124 (0.028), p < 0.001; folate: 0.128 (0.035), <0.001). Additionally, postpartum nutrient supplementation was associated with log-transformed serum folate level, especially for lactating women (ß (SE) = 0.204 (0.062), p = 0.001). Increased DDS was significantly associated with elevated serum vitamin B12 and folate levels (vitamin B12: ß (SE) = 0.028 (0.011), p = 0.011; folate: 0.030 (0.014), 0.031). In addition, age and educational level were influencing factors for serum vitamin B12 and folate concentrations among postpartum women. Conclusion: Serum vitamin B12 level decreased and folate level increased with postpartum age among Chinese women. Nutrient supplementation during pregnancy was related to elevated serum vitamin B12 and folate concentrations. Postpartum nutrient supplementation was associated with the increased serum folate level of lactating women. Dietary diversity was related to increased serum vitamin B12 and folate levels, especially among postpartum women with younger age and lower educational level.

Serum vitamin B12 and D levels in children with Primary Raynaud Phenomenon: a retrospective cohort study.

Primary Raynaud phenomenon (RP) is resultant from transient vasospasm of peripheral arteries and arterioles, is usually precipitated by cold exposure or emotional stress, without any clue for autoimmune connective tissue diseases. We aimed to determine the frequency of vitamin D and B12 deficiencies in pediatric patients with primary RP, and to investigate their roles on the disease course. Vitamin B12 and D were supplemented if the patients had deficiencies. The study included 40 children with primary RP, 29 (72.5%) female and 11 (27.5%) male. The mean and median age were 15.1 ± 1.8 and 15.5 (range, 11.5-17.8) years. Symptoms were improved in 31 (77.5%) patients with warming procedures. Seventeen (41.5%) and 16 (39%) patients had low serum vitamin B12 and D levels, respectively. Vasodilator treatment requirement did not change by vitamin B12 status but was significantly lower in vitamin D deficient and replaced patients. Further studies are needed to clarify our results.

Folate and vitamin B12 status: temporal evaluation after mandatory fortification in Brazil.

OBJECTIVES: To perform temporal evaluation of folate and vitamin B12 status and their associated factors in a Brazilian population exposed to mandatory fortification. METHODS: Data from the cross-sectional population-based studies 2008 and 2015 Health Surveys of São Paulo, including individuals ≥ 20 years, both sexes, N = 549 in 2008 and N = 610 in 2015. Folate and vitamin B12 biomarkers status, B-complex supplements and medications use, and dietary intake were assessed. RESULTS: Serum folate concentrations increased in the entire population, adults and older adults in 2015 compared to 2008, while serum vitamin B12 concentration increased only in older adults. B-complex supplement use raised in 2015, reflecting in serum vitamins status. Overall serum vitamin B12 deficiencies (<200 pg/mL) were 23.2% and 21.2%, while serum folate deficiencies (<4 ng/mL) were 4.1% and 1.5% in 2008 and 2015, respectively. The lowest quintile of serum folate (≤8.7 ng/mL) was positively associated with smoking and oral contraceptive use, while the highest quintile (≥17.8 ng/mL) was inversely associated with smoking and positively with B-complex supplement use. The odds of having vitamin B12 deficiency was inversely associated with B-complex supplement use, higher serum folate median, higher dietary vitamin B12 intake and positively associated with using oral contraceptive. CONCLUSION: Overall deficiency of folate has decreased in 2015, being almost non-existent. Low vitamin B12 status presented similar proportions in the overall population comparing both periods, except for older adults. Different predictive variables were identified to better understand vitamins status outcomes in the most recent period of the study.

Cross-Sectional Study of the Prevalence of Cobalamin Deficiency and Vitamin B12 Supplementation Habits among Vegetarian and Vegan Children in the Czech Republic.

Vegetarian (VG) and vegan (VN) diets in childhood are of growing interest due to their perceived health and environmental benefits. Concerns remain due to the possible disruption of healthy growth and development of children because of the scarcity of evidence-based studies. Among the nutrients of special concern is vitamin B12. Therefore, the Czech Vegan Children Study (CAROTS) decided to examine the relationship between B12 metabolism parameters and B12 intake through diet and supplementation. We analyzed laboratory parameters within n = 79 VG, n = 69 VN, and n = 52 omnivores (OM) children (0−18 years old). There were no significant differences in levels of holotranscobalamin (aB12), folate, homocysteine (hcys), or mean corpuscular volume. However, there was a significant difference in levels of cyanocobalamin (B12) (p = 0.018), even though we identified only n = 1 VG and n = 2 VN children as B12 deficient. On the other hand, we identified n = 35 VG, n = 28 VN, and n = 9 OM children with vitamin B12 hypervitaminosis (p = 0.004). This finding was related to a high prevalence of over-supplementation in the group (mean dose for VG 178.19 ± 238.5 µg per day; VN 278.35 ± 394.63 µg per day). Additionally, we found a significant (p < 0.05) difference between B12, aB12, and hcys levels of supplemented vs. non-supplemented VG/VN children. This can show that the intake of vitamin B12 via diet in the VG group might not be sufficient. Secondly, we analyzed a relation between supplement use in pregnancy and breastfeeding and its impact on vitamin B12 levels of children aged 0−3 years. Out of n = 46 mothers, only n = 3 (e.g., 6.5%) were not supplemented at all. We have not identified any clinical manifestation of B12 deficiency and only n = 1 child with low serum cobalamin, a child who did not receive vitamin B12 supplementation and whose mother took only low doses of vitamin B12 (25/µg/day).To conclude, we did not observe any life-threatening or severe consequences of laboratory-stated vitamin B12 deficiency; thus, our group was well supplemented. On the other hand, we have identified many subjects with vitamin B12 hypervitaminosis of unknown impact on their health. Further research and new guidelines for B12 supplementation among VG and VN children are needed.

RBC Folate and Serum Folate, Vitamin B-12, and Homocysteine in Chinese Couples Prepregnancy in the Shanghai Preconception Cohort.

BACKGROUND: The protective effects of maternal folate on neural tube defects are well-established. Emerging evidence has shown paternal folate also is related to pregnancy outcome and offspring health. OBJECTIVES: This study aimed to assess the status of red blood cell (RBC) folate and serum folate, vitamin B-12, and homocysteine (Hcy) and their associated factors in a cohort of pregnancy-preparing couples. METHODS: This was a cross-sectional study involving 14,178 participants from the extension of the Shanghai Preconception Cohort conducted in 2018-2021. Circulating biomarker concentrations were measured, and the prevalence of abnormal status was reported. Linear and logistic regression analyses were conducted to examine associations of demographic factors (age, education, and income), lifestyle factors (smoking, drinking, and folic acid supplement use), and BMI with concentrations of the folate-related biomarkers, abnormal status of folate (deficiency and insufficiency) and vitamin B-12 (deficiency and marginal deficiency), and hyperhomocysteinemia. RESULTS: The geometric mean (95% CI) concentrations of RBC folate, serum folate, vitamin B-12, and Hcy were 490 nmol/L (485, 496 nmol/L), 20.1 nmol/L (19.8, 20.3 nmol/L), 353 pmol/L (350, 357 pmol/L), and 7.54 µmol/L (7.48, 7.60 µmol/L) in females, respectively, and 405 nmol/L (401, 409 nmol/L), 13.5 nmol/L (13.4, 13.7 nmol/L), 277 pmol/L (274, 279 pmol/L), and 12.0 µmol/L (11.9, 12.2 µmol/L) in males, respectively. Prevalence of abnormal status was higher in males than females for the 4 folate-related biomarkers: RBC folate deficiency (<340 nmol/L, 32.2% compared with 18.9%), serum folate deficiency (<10.0 nmol/L, 26.5% compared with 7.3%), RBC folate insufficiency (<906 nmol/L, 96.6% compared with 90.1%), serum folate insufficiency (<15.9 nmol/L, 65.5% compared with 31.4%), vitamin B-12 marginal deficiency (148-221 pmol/L, 21.4% compared with 8.8%), and hyperhomocysteinemia (>15.0 µmol/L, 22.1% compared with 2.5%). CONCLUSIONS: Most pregnancy-preparing couples failed to achieve the optimal RBC folate status (>906 nmol/L) as recommended by the WHO. These findings call for attention to the insufficiency status of folate and promising strategies to improve the folate status of the pregnancy-preparing population not exposed to folic acid fortification.

Hematinic deficiency in patients with heart failure with reduced ejection fraction (HFrEF).

BACKGROUND AND OBJECTIVES: Hematinic deficiency irrespective of anemia is not uncommon in patients with heart failure. We studied the prevalence, distribution, and etiology of anemia in patients with heart failure with reduced ejection fraction (HFrEF) and compared it with non-anemic patients. METHODS: Congestive heart failure (CHF) was diagnosed by modified Framingham criteria and ejection fraction (EF) <40%. Iron deficiency (ID) anemia was defined as serum ferritin level <100 ng/ml (absolute) or 100-300 ng/ml with transferrin saturation <20% (functional). Vitamin B12 and folate deficiency were defined as <200pg/ml and <4ng/ml respectively. RESULT: 688 patients with HFrEF were studied with an overall mean age of 57.2±13.8 years, and males outnumbering females (62.3% vs. 37.7%). Coronary artery disease (44.2%), dilated cardiomyopathy (46.8%), and valvular heart disease (6.7%) were major causes of CHF.Anemia was found in 63.9% of patients. Vit B12 deficiency, and folate deficiency were found in 107 (15.55%), and 54 (7.85%) subjects, respectively. Absolute ID was detected in 186 (42.27%) patients with anemia and 84 (33.87%) patients without anemia, while functional ID was present in 80 (18.18%) patients with anemia and 29 (11.69%) patients without anemia. Vitamin B12 deficiency was noted in 70 (15.9%) patients with anemia and 37 (14.9%) patients without anemia, while folate deficiency was noted in 31 (7.04%) patients with anemia and 23 (9.2%) patients without anemia. Hematinic deficiency among the study population was distributed equally among patients irrespective of EF, NYHA class, socioeconomic class diet pattern. CONCLUSION: The study shows that hematinic deficiency was seen even in non-anemic patients irrespective of diet pattern. Supplementation could be a strong strategy to improve outcomes in these patients of heart failure irrespective of anemia and should be evaluated in prospective studies.

A rise in cases of nitrous oxide abuse: neurological complications and biological findings.

BACKGROUND: The recent lockdown due to the COVID-19 pandemic has been linked to a higher incidence of psychiatric manifestations and substance abuse. The recreative use of nitrous oxide is more and more widespread and neurological complications are frequent. METHODS: We report clinical characteristics and biological findings of five consecutive patients presenting to our tertiary care center between April 2020 and February 2021 with various neurological symptoms occurring after recent nitrous oxide abuse. RESULTS: Our patients presented with subacute combined degeneration of the spinal cord (4/5 patients) or with acute inflammatory demyelinating polyneuropathy (1/5 patients). No patient had reduced vitamin B-12 titer, but all had elevated blood levels of homocysteine and methylmalonic acid. This reflects the functional deficit in vitamin B-12 that can be linked to nitrous oxide consumption. After vitamin B-12 supplementation, clinical signs regressed at least partially in all 5 patients. CONCLUSION: We report an elevated incidence of neurological complications of nitrous oxide abuse occurring during the recent COVID-19 lockdown. Nitrous oxide abuse should be tracked down in patients presenting with compatible neurological symptoms and elevated homocysteinemia. Vitamin B-12 should be supplemented as soon as the diagnosis is made.

Vitamin B12 deficiency is associated with narcolepsy.

BACKGROUND: Narcolepsy can be defined as a sleep disorder. However, whether changes in the serum vitamin B12 levels are involved in the pathophysiological mechanism of narcolepsy remains unclear. Our study aimed to assess whether vitamin B12 levels are independently related to the occurrence of narcolepsy. METHODS: The serum folate, vitamin B12, and homocysteine levels of 40 patients with narcolepsy and 40 age- and gender-matched healthy controls (HC) were retrospectively analyzed. According to the results of the univariate logistic analysis, a multiple logistic regression model was constructed to predict the independent influencing indicators. RESULTS: Serum folic acid and vitamin B12 levels in the narcolepsy group were significantly reduced. Moreover, through the sex subgroup, males in the narcolepsy group had lower serum vitamin B12 levels. Multivariate logistic regression revealed serum vitamin B12 to be independently associated with narcolepsy (p < 0.05; odds ratio=0.97; 95% confidence interval: 0.95-0.98). CONCLUSION: Decreased serum vitamin B12 levels are independently associated with the development of narcolepsy, which illustrates the complex relationship between vitamin B12 and narcolepsy. Future studies should explore whether vitamin B12 supplementation can improve the symptoms of patients.

Vitamin B-12 Intake from Dairy but Not Meat Is Associated with Decreased Risk of Low Vitamin B-12 Status and Deficiency in Older Adults from Quebec, Canada.

BACKGROUND: Vitamin B-12 deficiency can result in irreversible neurologic damages. It is most prevalent among older adults (∼5%-15%), mainly due to impaired absorption. Vitamin B-12 bioavailability varies between food sources, so their importance in preventing deficiency may also vary. OBJECTIVES: Using the NuAge Database and Biobank, we examined the associations between vitamin B-12 intake (total and by specific food groups) and low vitamin B-12 status and deficiency in older adults. METHODS: NuAge-the Quebec Longitudinal Study on Nutrition and Successful Aging-included 1753 adults aged 67-84 y who were followed 4 y. Analytic samples comprised 1230-1463 individuals. Dietary vitamin B-12 intake was assessed annually using three 24-h dietary recalls. Vitamin B-12 status was assessed annually as low serum vitamin B-12 (<221 pmol/L), elevated urinary methylmalonic acid (MMA)/creatinine ratio (>2 µmol/mmol), and a combination of both (deficiency). Vitamin B-12 supplement users were excluded. Multilevel logistic regressions, adjusted for relevant confounders, were used. RESULTS: Across all study years, 21.8%-32.5% of participants had low serum vitamin B-12, 12.5%-17.0% had elevated urine MMA/creatinine, and 10.1%-12.7% had deficiency. Median (IQR) total vitamin B-12 intake was 3.19 µg/d (2.31-4.37). Main sources were "dairy" and "meat, poultry, and organ meats." The ORs (95% CIs) in the fifth quintile compared with the first of total vitamin B-12 intake were as follows: for low serum vitamin B-12, 0.52 (0.37, 0.75; P-trend < 0.0001); for elevated urine MMA/creatinine, 0.63 (0.37, 1.08; P-trend = 0.091); and for vitamin B-12 deficiency, 0.38 (0.18, 0.79; P-trend = 0.006). Similarly, ORs (95% CIs) in the fourth quartile compared with the first of dairy-derived vitamin B-12 intake were 0.46 (0.32, 0.66; P-trend < 0.0001), 0.51 (0.30, 0.87; P-trend = 0.006), and 0.35 (0.17, 0.73; P-trend = 0.003), respectively. No associations were observed with vitamin B-12 from "meat, poultry, and organ meats." CONCLUSIONS: Higher dietary vitamin B-12 intake, especially from dairy, was associated with decreased risk of low vitamin B-12 status and deficiency in older adults. Food groups might contribute differently at reducing risk of deficiency in older populations.

Association of air pollution and homocysteine with global DNA methylation: A population-based study from North India.

BACKGROUND: Anthropogenic air pollution has been implicated in aberrant changes of DNA methylation and homocysteine increase (>15µM/L). Folate (<3 ng/mL) and vitamin B12 (<220 pg/mL) deficiencies also reduce global DNA methylation via homocysteine increase. Although B-vitamin supplements can attenuate epigenetic effects of air pollution but such understanding in population-specific studies are lacking. Hence, the present study aims to understand the role of air pollution, homocysteine, and nutritional deficiencies on methylation. METHODS: We examined cross-sectionally, homocysteine, folate, vitamin B12 (chemiluminescence) and global DNA methylation (colorimetric ELISA Assay) among 274 and 270 individuals from low- and high- polluted areas, respectively, from a single Mendelian population. Global DNA methylation results were obtained on 254 and 258 samples from low- and high- polluted areas, respectively. RESULTS: Significant decline in median global DNA methylation was seen as a result of air pollution [high-0.84 (0.37-1.97) vs. low-0.96 (0.45-2.75), p = 0.01]. High homocysteine in combination with air pollution significantly reduced global DNA methylation [high-0.71 (0.34-1.90) vs. low-0.93 (0.45-3.00), p = 0.003]. Folate deficient individuals in high polluted areas [high-0.70 (0.37-1.29) vs. low-1.21 (0.45-3.65)] showed significantly reduced global methylation levels (p = 0.007). In low polluted areas, despite folate deficiency, if normal vitamin B12 levels were maintained, global DNA methylation levels improved significantly [2.03 (0.60-5.24), p = 0.007]. Conversely, in high polluted areas despite vitamin B12 deficiency, if normal folate status was maintained, global DNA methylation status improved significantly [0.91 (0.36-1.63)] compared to vitamin B12 normal individuals [0.54 (0.26-1.13), p = 0.04]. CONCLUSIONS: High homocysteine may aggravate the effects of air pollution on DNA methylation. Vitamin B12 in low-polluted and folate in high-polluted areas may be strong determinants for changes in DNA methylation levels. The effect of air pollution on methylation levels may be reduced through inclusion of dietary or supplemented B-vitamins. This may serve as public level approach in natural settings to prevent metabolic adversities at community level.

Perspective: Practical Approach to Preventing Subclinical B12 Deficiency in Elderly Population.

Vitamin B12 (also known as cobalamin) is an essential water-soluble vitamin that plays a pivotal role for several physiologic functions during one's lifespan. Only certain microorganisms are able to synthetize B12, thus humans obtain cobalamin exclusively from their diet, specifically from animal-derived foods. Specific sub-group populations are at risk of vitamin B12 subclinical deficiency due to different factors including poor intake of animal source foods and age-dependent decrease in the capacity of intestinal B12 uptake. Consumption of animal products produces some negative health issues and negatively impacts sustainability while a plant-based diet increases the risk of B12 deficiency. Taking a cue from the aforementioned considerations, this narrative review aims to summarize facts about B12 deficiency and the burden of inadequate dietary intake in elderly population, as well as to discuss sustainable approaches to vitamin B12 deficiency in aging population.