Associations of atrophic gastritis and proton-pump inhibitor drug use with vitamin B-12 status, and the impact of fortified foods, in older adults.

BACKGROUND: Atrophic gastritis (AG) and use of proton pump inhibitors (PPIs) result in gastric acid suppression that can impair the absorption of vitamin B-12 from foods. The crystalline vitamin B-12 form, found in fortified foods, does not require gastric acid for its absorption and could thus be beneficial for older adults with hypochlorhydria, but evidence is lacking. OBJECTIVES: To investigate associations of AG and PPI use with vitamin B-12 status, and the potential protective role of fortified foods, in older adults. METHODS: Eligible participants (n = 3299) not using vitamin B-12 supplements were drawn from the Trinity-Ulster and Department of Agriculture cohort, a study of noninstitutionalized adults aged ≥60 y and recruited in 2008-2012. Vitamin B-12 status was measured using 4 biomarkers, and vitamin B-12 deficiency was defined as a combined indicator value < -0.5. A pepsinogen I:II ratio <3 was considered indicative of AG. RESULTS: AG was identified in 15% of participants and associated with significantly lower serum total vitamin B-12 (P < 0.001) and plasma holotranscobalamin (holoTC; P < 0.001), and higher prevalence of vitamin B-12 deficiency (38%), compared with PPI users (21%) and controls (without AG and nonusers of PPIs; 15%; P < 0.001). PPI drugs were used (≥6 mo) by 37% of participants and were associated with lower holoTC concentrations, but only in participants taking higher doses (≥30 mg/d). Regular, compared with nonregular, consumption of fortified foods (i.e., ≥5 and 0-4 portions/wk, respectively) was associated with higher vitamin B-12 biomarkers in all participants, but inadequate to restore normal vitamin B-12 status in those with AG. CONCLUSIONS: Older adults who have AG and/or use higher doses of PPIs are more likely to have indicators of vitamin B-12 deficiency. Fortified foods, if consumed regularly, were associated with enhanced vitamin B-12 status, but higher levels of added vitamin B-12 than currently provided could be warranted to optimize status in people with AG.

Reducing the Risk of Stroke in Patients with Impaired Renal Function: Nutritional Issues.

Patients with renal failure have extremely high cardiovascular risk; in dialysis patients the risk of stroke is increased approximately 10-fold over that in the general population. Reasons include not only a high prevalence of traditional risk factors such as diabetes, hypertension and dyslipidemia, but also the accumulation of toxic substances that are eliminated by the kidneys, so have very high levels in patients with renal failure. These include plasma total homocysteine, asymmetric dimethylarginine, thiocyanate, and toxic products of the intestinal microbiome (Gut-Derived Uremic Toxins; GDUT), which include trimethylamine N- oxide (TMAO), produced from phosphatidylcholine (largely from egg yolk) and carnitine (largely from red meat). Other GDUT are produced from amino acids, largely from meat consumption. Deficiency of vitamin B12 is very common, raises plasma tHcy, and is easily treated. However, cyanocobalamin is toxic in patients with renal failure. To reduce the risk of stroke in renal failure it is important to limit the intake of meat, avoid egg yolk, and use methylcobalamin instead of cyanocobalamin, in addition to folic acid.

La dieta vegetariana en niños y preadolescentes / Vegetarian diet in children and pre-adolescents

Basándonos en una consulta de una niña que desea realizar una dieta vegetariana se realizó una búsqueda bibliográfica para identificar evidencia sobre el impacto de este tipo de dieta en la salud. La evidencia actual indica que la dieta vegetariana es una opción saludable que no produciría un impacto negativo en el crecimiento y desarrollo de los niños, si bien existiría la posibilidad de déficit de micronutrientes. (AU)

Based on a consultation of a girl who wishes to make a vegetarian diet, a literature search was conducted to identify evidence on the impact of this type of diet on health. Current evidence indicates that the vegetarian diet is a healthy option that would not have a negative impact on the growth and development of children, although there is a possibility of micronutrient deficits. (AU)

Cyano-B12 or Whey Powder with Endogenous Hydroxo-B12 for Supplementation in B12 Deficient Lactovegetarians.

Lactovegetarians (n = 35) with low vitamin B12 (B12) status were intervened for eight weeks capsules containing cyano-B12 (CN-B12), (2 × 2.8 µg/day), or equivalent doses of endogenous B12 (mainly hydroxo-B12 (HO-B12)) in whey powder. Blood samples were examined at baseline, every second week during the intervention, and two weeks post-intervention. The groups did not differ at baseline in [global median (min/max)] plasma B12 [112(61/185)] pmol/L, holotranscobalamin [20(4/99)] pmol/L, folate [13(11/16)], the metabolites total homocysteine [18(9/52)] µmol/L and methylmalonic acid [0.90(0.28/2.5)] µmol/L, and the combined indicator of B12 status (4cB12) [-1.7(-3.0/-0.33)]. Both supplements caused significant effects, though none of the biomarkers returned to normal values. Total plasma B12 showed a higher increase in the capsule group compared to the whey powder group (p = 0.02). However, the increase of plasma holotranscobalamin (p = 0.06) and the lowering of the metabolites (p > 0.07) were alike in both groups. Thereby, the high total plasma B12 in the capsule group was not mirrored in enhanced B12 metabolism, possibly because the B12 surplus was mainly accumulated on an "inert" carrier haptocorrin, considered to be of marginal importance for tissue delivery of B12. In conclusion, we demonstrate that administration of whey powder (HO-B12) or capsules (CN-B12) equivalent to 5.6 µg of B12 daily for eight weeks similarly improves B12 status but does not normalize it. We document that the results for plasma B12 should be interpreted with caution following administration of CN-B12, since the change is disproportionately high compared to the responses of complementary biomarkers.

Improvement of vitamin B12 status with Spirulina supplementation in Wistar rats validated through functional and circulatory markers.

Spirulina evaluated as a source of vitamin B12 through the modulation of vitamin B12 deficiency mediated physiological and biochemical changes in experimental animals. The B12 deficient male weanling Wistar rats were fed with Spirulina-supplemented diet for 10 weeks. An increase in urinary methylmalonic acid (22.70 ± 4.08 µmol/moles of creatinine) and plasma homocysteine (16.55 ± 0.48 µmol/L) levels in the B12 deficient group was observed, while these were equal to control in the Spirulina fed group (8.71 ± 0.48 µmol/mol of creatinine and 6.88 ± 1.18 µmol/L, respectively). The vitamin B12 levels in serum (874.27 ± 89.69), plasma (615.53 ± 26.5 pg/ml), kidney (10.19 ± 1.066 ng/g), and liver tissues (6.37 ± 0.62 ng/g) in the Spirulina fed group were similar to control. Severe atrophic changes in the testes and altered tissue architecture in lung and spleen as seen in the B12 deficient group were normalized in the Spirulina fed group. The study validates that Spirulina can improve the vitamin B12 status. PRACTICAL APPLICATIONS: The present study showed that the supplementation of Spirulina in the diet of vitamin B12 deficient rats leads to the normalization of vitamin B12 deficiency-induced circulatory and functional biomarkers along with biochemical and histological changes. Vegetarian sources for vitamin B12 are limited and the results presented here provide scientific validation for the use of Spirulina as a potential vegetarian source of bioavailable vitamin B12 .

Effects of dietary intervention on vitamin B12 status and cognitive level of 18-month-old toddlers in high-poverty areas: a cluster-randomized controlled trial.

BACKGROUND: The local diet in high-poverty areas in China is mainly vegetarian, and children may be more vulnerable to vitamin B12 deficiency. OBJECTIVE: The aims of this study were to explore the vitamin B12 status of toddlers living in high-poverty areas of China and to observe the effects of different complementary foods on the vitamin B12 status and cognitive level of these toddlers. METHODS: The study was nested within a cluster-randomized controlled trial implemented in 60 administrative villages (clusters) of Xichou County in which infants aged 6 months old were randomized to receive 50 g/d of pork (meat group), an equi-caloric fortified cereal supplement (fortified cereal group) or local cereal supplement (local cereal group) for one year. At 18 months, a subsample of the 180 toddlers (60 from each group) was randomly tested for serum vitamin B12 and total homocysteine (tHcy) levels, and their neurodevelopment was evaluated. RESULTS: The median serum concentrations of vitamin B12 and tHcy were 360.0 pg/mL and 8.2 µmol/L, respectively, in children aged 18 months. Serum vitamin B12 concentrations less than 300 pg/mL were found in 62 (34.4%) children, and concentrations less than 200 pg/mL were found in 30 (16.7%) children. The median vitamin B12 concentration was significantly different among the three groups (P < 0.001). The highest vitamin B12 level was demonstrated in the fortified cereal group (509.5 pg/mL), followed by the meat group (338.0 pg/mL) and the local cereal group (241.0 pg/mL). Vitamin B12 concentration was positively correlated with the cognitive score (P < 0.001) and the fine motor score (P = 0.023) of the Bayley Scales of Infant Development, 3rd Edition (BSID III) screening test. Compared to the local cereal group, children in the meat group had higher cognitive scores (P < 0.05). CONCLUSION: In poor rural areas of China, vitamin B12 deficiency in toddlers was common due to low dietary vitamin B12 intake. Fortified cereal and meat could help improve the vitamin B12 status of children and might improve their cognitive levels. TRIAL REGISTRATION: The larger trial in which this study was nested was registered at clinical trials.gov as NCT00726102 . It was registered on July 31, 2008.

Methylmalonic Acid Levels and their Relation with Cobalamin Supplementation in Spanish Vegetarians.

Cobalamin deficiency represents a health issue for vegetarians, especially vegans, if supplements are not consumed. Vitamin B12 serum levels, traditionally used to assess the vitamin B12 status, can be normal under functional deficiency conditions. In this regard, methylmalonic acid (MMA) has proven to be a more specific marker to detect subclinical vitamin B12 deficiency. In this study, we present for the first time the cobalamin status of Spanish vegetarians using both vitamin B12 and MMA markers, and the effects of the plant-based diet and the intake of vitamin B12 supplements. Healthy adults were recruited (n = 103, 52% vegans). Dietary preferences and use of supplements were assessed by questionnaires and serum samples were collected and stored. Vitamin B12 was measured by chemiluminiscence and MMA by liquid chromatography tandem mass spectrometry (LC-MS/MS) using solid phase extraction for sample preparation. Obtained values, median (IQR), were: vitamin B12, 278.9 (160.2) pmol/l and MMA, 140.2 (78.9) nmol/l. No significant differences between lacto-ovo vegetarians and vegans were observed. Considering these two markers, 10% of the participants were mild vitamin B12 deficient. Supplementation (75% of the participants) was associated with higher vitamin B12 (p < 0.001) and lower MMA (p = 0.012). In conclusion, Spanish vegetarians have low risk of vitamin B12 deficiency due to vitamin B12 supplementation and the MMA determination is useful to detect mild deficiency.

Evaluation of tracer labelled methionine load test in vitamin B-12 deficient adolescent women.

BACKGROUND: Methionine loading test (MLT) has been used primarily to identify defects in transsulfuration of homocysteine in cystathionine beta synthase deficiency. It may not be as useful to evaluate remethylation pathway, in vitamin B-12 and folate deficiencies. OBJECTIVE: We used tracer isotope labelled MLT to interrogate transsulfuration and remethylation independently in vitamin B-12 deficiency. DESIGN: We studied vitamin B-12 deficient women with a tracer labelled MLT before and eleven months after treatment with vitamin B-12. The fractional contribution of [13C]homocysteine to breath CO2 was used as a measure of transsulfuration, and difference in the intracellular enrichment of [13C]methionine and that of [C2H3]methionine as a measure of remethylation of homocysteine. Combined pre- and post-treatment results were analyzed to investigate the association between plasma vitamin B-12 concentrations and measures of homocysteine metabolism. RESULTS: The subjects were 17 years old, with a BMI of 19.4 kg/m2. Treatment with vitamin B-12, 2µg/day increased plasma B-12 from 93 (78.7, 106.2) [median (25th, 75th centiles)] to 161.5 (125.5, 226.2) pmol/L; 44% were below <150pmol/L after treatment. Fasting homocysteine concentration was significantly lower and that of cysteine higher in subjects with B-12 levels >150pmol/L. The tracer estimated transsulfuration of homocysteine was lower and remethylation higher with B-12 levels >150pmol/L when compared with those <150pmol/L. CONCLUSIONS: The tracer labelled MLT in combination with fasting parameters is a robust way to estimate parameters of methionine metabolism and can be used in the field where prime-constant rate infusion studies cannot be done efficiently.

Vitamin B12 deficiency: unusual cause of jaundice in an adolescent.

Vitamin B12 deficiency in vegans is a known cause of megaloblastic anaemia. We report an adolescent girl who presented with jaundice and weight loss for 6 months secondary to vitamin B12 deficiency, leading to megaloblastic anaemia. Replacement with vitamin B12 reversed her symptoms, resulting in weight gain, and normalised her haemoglobin, red blood cell morphology, bilirubin levels and serum vitamin B12 levels.

Evidence From Web-Based Dietary Search Patterns to the Role of B12 Deficiency in Non-Specific Chronic Pain: A Large-Scale Observational Study.

BACKGROUND: Profound vitamin B12 deficiency is a known cause of disease, but the role of low or intermediate levels of B12 in the development of neuropathy and other neuropsychiatric symptoms, as well as the relationship between eating meat and B12 levels, is unclear. OBJECTIVE: The objective of our study was to investigate the role of low or intermediate levels of B12 in the development of neuropathy and other neuropsychiatric symptoms. METHODS: We used food-related Internet search patterns from a sample of 8.5 million people based in the US as a proxy for B12 intake and correlated these searches with Internet searches related to possible effects of B12 deficiency. RESULTS: Food-related search patterns were highly correlated with known consumption and food-related searches (ρ=.69). Awareness of B12 deficiency was associated with a higher consumption of B12-rich foods and with queries for B12 supplements. Searches for terms related to neurological disorders were correlated with searches for B12-poor foods, in contrast with control terms. Popular medicines, those having fewer indications, and those which are predominantly used to treat pain, were more strongly correlated with the ability to predict neuropathic pain queries using the B12 contents of food. CONCLUSIONS: Our findings show that Internet search patterns are a useful way of investigating health questions in large populations, and suggest that low B12 intake may be associated with a broader spectrum of neurological disorders than previously thought.

Effects of medical food leucine content in the management of methylmalonic and propionic acidemias.

PURPOSE OF REVIEW: The current review highlights the varied effects of medical foods high in leucine (Leu) and devoid of valine (Val) and isoleucine (Ile) in the management of methylmalonic acidemia (MMA) and propionic acidemia and cobalamin C (cblC) deficiency, aiming to advance dietary practices. RECENT FINDINGS: Leu is a key metabolic regulator with a multitude of effects on different organ systems. Recent observational studies have demonstrated that these effects can have unintended consequences in patients with MMA as a result of liberal use of medical foods. The combination of protein restriction and medical food use in MMA and propionic acidemia results in an imbalanced branched-chain amino acid (BCAA) dietary content with a high Leu-to-Val and/or Ile ratio. This leads to decreased plasma levels of Val and Ile and predicts impaired brain uptake of multiple essential amino acids. Decreased transport of methionine (Met) across the blood-brain barrier due to high circulating Leu levels is of particular concern in cblC deficiency in which endogenous Met synthesis is impaired. SUMMARY: Investigations into the optimal composition of medical foods for MMA and propionic acidemia, and potential scenarios in which Leu supplementation may be beneficial are needed. Until then, MMA/propionic acidemia medical foods should be used judiciously in the dietary management of these patients and avoided altogether in cblC deficiency.

An Animal-Source Food Supplement Increases Micronutrient Intakes and Iron Status among Reproductive-Age Women in Rural Vietnam.

Background: Few studies have examined the impact of local animal-source foods (ASFs) on the nutritional status of reproductive-age women in developing countries.Objective: We hypothesized that a midmorning snack of local ASF for 6 mo would reduce dietary micronutrient deficiencies [usual intake less than the estimated average requirement (EAR)] and improve blood biomarkers of iron, zinc, and vitamins A and B-12 status among nonpregnant, reproductive-age women in rural Vietnam.Methods: One hundred seventeen women, 18-30 y old, were randomly assigned to receive either an ASF (mean: 144 kcal, 8.9 mg Fe, 2.7 mg Zn, 1050 µg retinoic acid equivalent vitamin A, and 5.5 µg vitamin B-12) or a control snack (mean: 150 kcal, 2.0 mg Fe, 0.9 mg Zn, 0 µg retinoic acid equivalent vitamin A, and 0 µg vitamin B-12) 5 d/wk for 6 mo. Usual nutrient intakes were estimated by repeated 24-h dietary recalls. Blood samples were collected at baseline and 3 and 6 mo. Because of the relation between nutritional status and inflammation, serum C-reactive protein, α-1-acid-glycoprotein, and urinary tract infections (UTIs) were also monitored.Results: Eighty-nine women (47 in the ASF group and 42 controls) completed the study. In the ASF group, intakes of iron and vitamins A and B-12 below the EAR were eliminated, and the prevalence of a low zinc intake was reduced to 9.6% compared with 64.7% in controls (P < 0.001). At 6 mo, a modest increase (P < 0.05) in hemoglobin and iron status occurred in the ASF group compared with the control group, but plasma zinc, retinol, and serum vitamin B-12 concentrations did not differ. UTI relative risk was 3.9 (P < 0.05) among women assigned to the ASF group who had a low whole-body iron status at baseline.Conclusions: Adding a small amount of locally produced ASF to the diets of reproductive-age Vietnamese women improved micronutrient intakes and iron status. However, the increased UTI incidence in women in the ASF group with initially lower iron stores warrants further investigation.

Combined Vitamin B-12 and Balanced Protein-Energy Supplementation Affect Homocysteine Remethylation in the Methionine Cycle in Pregnant South Indian Women of Low Vitamin B-12 Status.

Background: Low-quality dietary protein intake and vitamin B-12 deficiency could interact to decrease methionine transmethylation and remethylation rates during pregnancy and may affect epigenetic modifications of the fetal genome.Objective: The objective of this randomized, partially open-labeled intervention trial was to examine the effect of supplemental high-quality protein and vitamin B-12 on third-trimester methionine kinetics in pregnant Indian women with a low vitamin B-12 status.Methods: Pregnant women with low serum vitamin B-12 concentrations (<200 pmol/L) were randomly assigned to 1 of 3 groups: the first group received balanced protein-energy supplementation of 500 mL milk/d plus a 10-µg vitamin B-12 tablet/d (M+B-12 group; n = 30), the second group received milk (500 mL/d) plus a placebo tablet (M+P group; n = 30), and the third group received a placebo tablet alone (P group; n = 33). Third-trimester fasting plasma amino acid kinetics were measured by infusing 1-13C,methyl-2H3-methionine, ring-2H5-phenylalanine, ring-2H4-tyrosine,1-13C-glycine, and 2,3,3-2H3,15N-serine in a subset of participants. Placental mRNA expression of genes involved in methionine pathways, placental long interspersed nuclear elements 1 (LINE-1) methylation, and promoter methylation levels of vascular endothelial growth factor (VEGF) were analyzed.Results: Remethylation rates in the M+B-12, M+P, and P groups were 5.1 ± 1.7, 4.1 ± 1.0, and, 5.0 ± 1.4 µmol ⋅ kg-1 ⋅ h-1, respectively (P = 0.057), such that the percentage of transmethylation remethylated to methionine tended to be higher in the M+B-12 group (49.5% ± 10.5%) than in the M+P group (42.3% ± 8.4%; P = 0.053) but neither differed from the P group (44.2% ± 8.1%; P > 0.1). Placental mRNA expression, LINE-1, and VEGF promoter methylation did not differ between groups.Conclusions: Combined vitamin B-12 and balanced protein-energy supplementation increased the homocysteine remethylation rate in late pregnancy. Thus, vitamin B-12 along with balanced protein-energy supplementation is critical for optimal functioning of the methionine cycle in the third trimester of pregnancy in Indian women with low serum vitamin B-12 in early pregnancy. This trial was registered at clinicaltrials.gov as CTRI/2016/01/006578.

Associations between Folate and Vitamin B12 Levels and Inflammatory Bowel Disease: A Meta-Analysis.

BACKGROUND: Inflammatory bowel disease (IBD) patients may be at risk of vitamin B12 and folate insufficiencies, as these micronutrients are absorbed in the small intestine, which is affected by IBD. However, a consensus has not been reached on the association between IBD and serum folate and vitamin B12 concentrations. METHODS: In this study, a comprehensive search of multiple databases was performed to identify studies focused on the association between IBD and serum folate and vitamin B12 concentrations. Studies that compared serum folate and vitamin B12 concentrations between IBD and control patients were selected for inclusion in the meta-analysis. RESULTS: The main outcome was the mean difference in serum folate and vitamin B12 concentrations between IBD and control patients. Our findings indicated that the average serum folate concentration in IBD patients was significantly lower than that in control patients, whereas the mean serum vitamin B12 concentration did not differ between IBD patients and controls. In addition, the average serum folate concentration in patients with ulcerative colitis (UC) but not Crohn's disease (CD) was significantly lower than that in controls. This meta-analysis identified a significant relationship between low serum folate concentration and IBD. CONCLUSIONS: Our findings suggest IBD may be linked with folate deficiency, although the results do not indicate causation. Thus, providing supplements of folate and vitamin B12 to IBD patients may improve their nutritional status and prevent other diseases.

Study Exploring the Effects of Daily Supplementation with 400 µg of Folic Acid on the Nutritional Status of Folate in Women of Reproductive Age.

BACKGROUND: This investigation determines the nutritional state of serum and red blood cell (RBC) folate concentration and their relation with intake of folate, B6 ,and B12 , with serum vitamin B12 , and with genetic variants after provision of 400 µg/day of folic acid for 3 months to a group of 34 Colombian women of reproductive age. METHODS: We evaluated nutrient intake using 24-hr recall, assessing the levels of serum folate, RBC folate, serum B12 , and homocysteine, as well as determining genetic variants of the enzyme MTHFR (C677T and A1298C) and CßS (844ins68pb). RESULTS: The results show that following intake of 400 µg/day of folic acid, the risk of folate deficiency as seen in regular dietary intake disappears and the nutritional status of this nutrient is increased (p < 0.001). With respect to vitamin B12, the risk of serum deficiency with folic acid consumption increased slightly, and those that were found to be B12 deficient after supplementation also had decreased levels of serum homocysteine. Genetic factors did not influence the nutritional status of folate, although an association was found between the intake of nutrients and biochemical indicators. CONCLUSION: Given the results of our study, subsequent studies evaluating folic acid supplementation should also consider evaluating the status of B12 and B6 , and serum and RBC folate, as they participate interdependently in the cycle of folate and methionine and in homocysteine metabolism.Birth Defects Research 109:564-573, 2017.© 2017 Wiley Periodicals, Inc.

Efficacy of early treatment in patients with cobalamin C disease identified by newborn screening: a 16-year experience.

PURPOSE: Despite implementation of newborn screening (NBS), outcomes in cobalamin C disease (cblC) remain poor. Therapy with hydroxycobalamin and betaine is widely used, but dietary recommendations vary among metabolic centers. We present a longitudinal analysis of the relationship between metabolic control, diet, and outcomes in a cohort of cblC patients. METHODS: We completed a retrospective analysis of 12 patients with cblC referred for abnormal NBS results and followed in our center between 1999 and 2015. RESULTS: Of the patients, 87.5% had intellectual disability and 75% had retinopathy; 16.7% had one episode of mild acidosis. However, no patients manifested major metabolic decompensation. Developmental outcomes correlated more closely with initial metabolic abnormalities than with long-term metabolic control. Increased intake of medical foods resulted in better control but also perturbations in the ratios of essential amino acids and lower z-scores for head circumference. We found no relationship between diet and cognitive outcomes. CONCLUSIONS: Although dietary therapy for cblC patients improves metabolic control, few patients experience metabolic decompensation regardless of diet. Increased incomplete protein intake is not correlated with improvements in outcomes. Overall, outcomes are poor despite early initiation of therapy and regardless of the dietary strategy used.Genet Med advance online publication 02 February 2017.

Different Supplementation Regimes to Treat Perioperative Vitamin B12 Deficiencies in Bariatric Surgery: a Systematic Review.

Vitamin B12 dosage in multivitamin supplementation in the current literature is quite variable. There is no consensus about the optimal treatment of vitamin B12 deficiency. A systematic literature search on different supplementation regimes to treat perioperative vitamin B12 deficiencies in bariatric surgery was performed. The methodological quality of ten included studies was rated using the Newcastle Ottawa scale and ranged from moderate to good. The agreement between the reviewers was assessed with a Cohen's kappa (0.69). The current literature suggests that 350 µg oral vitamin B12 is the appropriate dose to correct low vitamin B12 levels in many patients. Further research must focus on a better diagnosis of a vitamin B12 deficiency, the optimal dose vitamin B12 supplementation, and clinical relevance next to biochemical data.

Mujer de 42 años con pancitopenia / A 42 year-old woman with pancytopenia

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