ArticleLiterature Review

Vitamin B12 and health

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Abstract

To review recent evidence that suggests vitamin B12 is associated with risk reduction for some chronic diseases and birth defects. A MEDLINE search from 1999 to 2007 was performed using the key word vitamin B12. The most relevant articles (129) dealt with cardiovascular disease, cancer, mental health, and birth outcomes;most studies presented level II evidence. Vitamin B12 might confer health benefits; however, such benefits are difficult to ascertain because of the complementary functions of vitamin B12 and folic acid. Vitamin B12 might lower high homocysteine levels below a threshold level achieved by folic acid alone. Furthermore, the interactions between the nutritional environment and genotype might have an important influence on vitamin B12, chronic disease risk, and risk of neural tube defects. Vitamin B12 might help protect against chronic disease and neural tube defects, but more research, particularly in the area of nutritional genomics, is needed to determine how vitamin B12 might augment the benefits of folic acid. Some consideration should be given to the potential value of fortifying foods with vitamin B12 in addition to the current mandatory folic acid fortification of grains.

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... However, these gains are usually so challenging to determine due to the many additional roles of vitamin B12 working together with folic acid. They may reduce the extreme homocysteine levels below the threshold level attained by folic acid acting independently [5]. In sum, vitamin B12 may assist in the protection against persistent disease and neural tube defects. ...
... This vitamin is important for the formation of red blood cells, cell division, maintenance of a healthy nervous system, myelin synthesis, cellular growth and reproduction, as well as rapid synthesis of DNA. At the moment, the natural course of vitamin B12 deficiency is not properly understood [5], [6], [16]. Holotranscobalamin, otherwise referred to as active B12 is preferred in the identification of subclinical B12 deficiency. ...
... Such an assumption is possible since there are symptoms of vitamin B12 deficiency that are related to those of COVID-19 infection. Some of these symptoms include an increase in oxidative stress, activation of the coagulation cascade, homocysteine concentration, elevated lactate dehydrogenase, thrombocytopenia, intravascular coagulation thrombosis, low reticulocyte, vasoconstriction, as well as renal and pulmonary vasculoathies [5], [6], [16]. These symptoms can contribute to gastrointestinal, respiratory, and central nervous system disorders. ...
Article
Background: The link between immunity and nourishment is clearly known and special attention is being given to its role in the COVID-19 disease. Vitamin B12 is one of the dietary requirements necessary in the treatment of coronavirus patients. Coronavirus patients often show clinical symptoms, such as fever, cough, respiratory distress syndrome, gastrointestinal infection, and fatigue. It is sensible to suppose that COVID-19 affects cobalamin metabolism, impairs intestinal microbial proliferation, and contributes to symptoms of cobalamin deficiency. Such an assumption is based on the fact that there are signs and symptoms of vitamin B12 deficiency that are similar to those of a coronavirus infection. Based on these observations, it can be inferred that treatment with vitamin B12 can be useful in the recovery of COVID-19 patients. Case Report: A 42-year-old healthy female with no chronic illness presented with a 1-week history of pale, weakness and fatigue, cold sensation in the extremities, dizziness and feeling of depression. She was recently diagnosed with mild COVID-19 symptoms but recovered without the need for hospital admission. After recovery, she resumed working but recent symptoms brought her to the doctor’s office. Her laboratory findings revealed low Vitamin B. The attending doctor prescribed intramuscular daily vitamin B ampoules to replace and prevent further deterioration. The doses stopped when acute symptoms reduced, and normal levels were reached. Conclusion: Based on the outcome of the case, recovered COVID-19 patients need to be checked for vitamin B12 deficiency and treated in time to prevent possible deterioration.
... The most common symptoms of vitamin B12 deficiency are hematological and/or neurological disorders (5,6). Therefore, some risk factors of vitamin B12 deficiency have been investigated including lifestyle, age, and ethnic origin (7)(8)(9)(10)(11)(12)(13). Moreover, genetic predisposition was demonstrated in vitamin B12 deficiency. ...
... Vitamin B12 deficiency is a diet-related and slowly developing disorder. Consequently, low levels of vitamin B12 are associated with neurological and hematological disorders such as neural tube defects, cardiovascular diseases, dementia, as well as some types of cancer (8,16,28,34). However, genetic predisposition to vitamin B12 deficiency has been demonstrated in various studies (14)(15)(16)(17)(18)(19)(20)(21)(22). ...
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Article
Vitamin B12 (cobalamin) deficiency is a prevalent worldwide health concern. Several factors are associated with vitamin B12 deficiency including lifestyle, genetic predisposition, and malfunctions in the absorption and transport of vitamin B12. In the current case-control study, we aimed at investigating the association between MTHFR polymorphisms and vitamin B12 deficiency in a Jordanian population. Two polymorphic sites of the MTHFR gene (c.677C>T, rs1801133 and c.1286A>C, rs1801131) were analyzed using RFLP and DNA sequencing in a group of vitamin B12 deficient individuals (45 males and 55 females). As a control, 100 matching individuals (age and sex) with vitamin B12 levels > 200 ng/mL were also recruited for this study. The MTHFR c.677C>T variant was significantly associated with vitamin B12 deficiency in individuals from northern Jordan. The frequency of the homozygous MTHFR c.677C>T genotype was significantly higher in B12 deficient individuals in comparison with the control group (X Our results showed a significant association between homozygous MTHFR c.677C>T variant and T allele frequencies and vitamin B12 deficiency in the Jordanian population.
... Vitamin B 12 deficiency anemia most commonly results from malabsorption syndrome (primarily because of a lack of intrinsic factor) or inadequate consumption of the vitamin. 1 Older people and people with a vegetarian diet are at the highest risk for this form of anemia; up to 20% of older adults have been reported to have the condition. 1,2 The initial clinical presentation of vitamin B 12 deficiency anemia often includes non specific symptoms such as fatigue, weakness, paresthesias and vertigo. 2 Glossitis is present in up to 25% of cases, 3 initially presenting as inflammatory changes characterized by bright red plaques; it may then evolve into the atrophic form, noted as atrophy of the lingual papillae, affecting more than 50% of the tongue's surface. ...
... Vitamin B 12 deficiency anemia most commonly results from malabsorption syndrome (primarily because of a lack of intrinsic factor) or inadequate consumption of the vitamin. 1 Older people and people with a vegetarian diet are at the highest risk for this form of anemia; up to 20% of older adults have been reported to have the condition. 1,2 The initial clinical presentation of vitamin B 12 deficiency anemia often includes non specific symptoms such as fatigue, weakness, paresthesias and vertigo. 2 Glossitis is present in up to 25% of cases, 3 initially presenting as inflammatory changes characterized by bright red plaques; it may then evolve into the atrophic form, noted as atrophy of the lingual papillae, affecting more than 50% of the tongue's surface. 3 Reported oral symptoms include a burning sensation, pruritus, lingual paresthesia, glossodynia and dysgeusia. ...
... Vitamin B 12 deficiency anemia most commonly results from malabsorption syndrome (primarily because of a lack of intrinsic factor) or inadequate consumption of the vitamin. 1 Older people and people with a vegetarian diet are at the highest risk for this form of anemia; up to 20% of older adults have been reported to have the condition. 1,2 The initial clinical presentation of vitamin B 12 deficiency anemia often includes non specific symptoms such as fatigue, weakness, paresthesias and vertigo. 2 Glossitis is present in up to 25% of cases, 3 initially presenting as inflammatory changes characterized by bright red plaques; it may then evolve into the atrophic form, noted as atrophy of the lingual papillae, affecting more than 50% of the tongue's surface. ...
... Vitamin B 12 deficiency anemia most commonly results from malabsorption syndrome (primarily because of a lack of intrinsic factor) or inadequate consumption of the vitamin. 1 Older people and people with a vegetarian diet are at the highest risk for this form of anemia; up to 20% of older adults have been reported to have the condition. 1,2 The initial clinical presentation of vitamin B 12 deficiency anemia often includes non specific symptoms such as fatigue, weakness, paresthesias and vertigo. 2 Glossitis is present in up to 25% of cases, 3 initially presenting as inflammatory changes characterized by bright red plaques; it may then evolve into the atrophic form, noted as atrophy of the lingual papillae, affecting more than 50% of the tongue's surface. 3 Reported oral symptoms include a burning sensation, pruritus, lingual paresthesia, glossodynia and dysgeusia. ...
Article
A 61-year-old woman presented with a 6-month history of a persistent burning sensation on her tongue (Figure 1A). The patient was not taking any medications and had not been exposed to any new foods or oral hygiene products at the time her symptoms began. Our clinical diagnosis was glossitis. A cytologic evaluation did not show evidence of Candida species. Laboratory investigations to rule out underlying hematologic diseases showed macrocytic anemia and low levels of vitamin B12 (83 [normal 200–700] pg/mL), consistent with vitamin B12 deficiency anemia. The patient was referred to her primary care physician for further management of the condition. She received a single injection (1000 μg) of vitamin B12, which resulted in complete resolution of her symptoms and the normal clinical appearance of her tongue after 3 days (Figure 1B). The cause of the patient’s condition and her need for long-term supplementation remain under investigation. Figure 1: (A) Generalized dryness of the tongue of a 61-year-old woman with vitamin B12 deficiency, with atrophy (blue arrowheads) and erythematous plaques (white arrowheads). (B) Normal appearance of the tongue 3 days after the patient received a single injection ... Vitamin B12 deficiency anemia most commonly results from malabsorption syndrome (primarily because of a lack of intrinsic factor) or inadequate consumption of the vitamin.1 Older people and people with a vegetarian diet are at the highest risk for this form of anemia; up to 20% of older adults have been reported to have the condition.1,2 The initial clinical presentation of vitamin B12 deficiency anemia often includes nonspecific symptoms such as fatigue, weakness, paresthesias and vertigo.2 Glossitis is present in up to 25% of cases,3 initially presenting as inflammatory changes characterized by bright red plaques; it may then evolve into the atrophic form, noted as atrophy of the lingual papillae, affecting more than 50% of the tongue’s surface.3 Reported oral symptoms include a burning sensation, pruritus, lingual paresthesia, glossodynia and dysgeusia.3 Treatment is usually lifelong intramuscular or oral administration of vitamin B12.3
... In the recent literature limited evidence is available, indicating an augmented risk of gastrointestinal cancer related to celiac disease [30,31]. Nevertheless, a correlation between B12 deficiency and cancer remains a matter of strong controversy [32]. Despite deficiency diseases, an association of RAS with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome (PFAPA) was discussed [29]. ...
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Article
Recurrent aphthous stomatitis (RAS) is a common disease of the mouth. We wanted to find out if due to inflammation RAS may contribute to oral cancer. We analyzed data from the TriNetX database from patients with and without RAS and set oral squamous cell carcinoma (OSCC) as outcome. We found an association between RAS and the development of OSCC. These findings need to be interpreted cautiously, as RAS is not classified as a premalignant condition to date, and our applied methods have some limitations. We conclude that further clinical research is necessary and oral ulcers suspicious of OSCC should undergo biopsy as early as possible.
... Vitamin B12 acts as a cofactor of cytoplasmic methionine synthase and mitochondrial methylmalonyl-CoA mutase thus playing an important role in carbohydrate and normal fat metabolism, formation of red blood cells, the normal functioning of the nervous system and in the translocation of the methyl group in DNA synthesis [10]. Its deficiency has been linked to reduced cognitive function, Alzheimer's disease, ischemic stroke and megaloblastic anemia [11,12]. Vitamin B12 in animal products originates from B12-producing microbiota of ruminant or coprophagic animals or ingestion of B12-fortified animal feed, while fishes thrive essentially on algae, acquiring B12 through bacteria-algae symbiotic association [13]. ...
Article
Seaweeds have been gaining popularity in the Western world due to increased interest in alternative food sources and improving the nutritional profile and functionality of food products. This paper analyzed the omega-3 fatty acids such as eicosapentaenoic acid (EPA) and α-linoleic acid (ALA) and B12 vitamin content in the most common Baltic seaweeds. These nutrients have an important part in the human diet. Five seaweeds species (Fucus vesiculosus, Furcellaria lumbricalis, Cladophora glomerata, Pilayella littoralis and Ulva intestinalis) were sampled during April–May, June–July, and August–September. The fatty acids were determined by GC–MS whereas B12 content was analyzed by HPLC-UV. 16S rRNA amplification from community DNA and sequencing was carried out to evaluate B12 synthesizing microorganisms associated with the studied seaweeds. The results showed that F. vesiculosus (5.19 ± 0.32 mg/gDW) was the best source of EPA, followed by F. lumbricalis, C. glomerata, P. littoralis and U. intestinalis irresponsibly of sampling time. The ALA content had little variability between species (1.07–2.45 mg/ g DW). The B12 concentration varied across seasons, being generally lowest during the June–July period. The highest concentration of B12 across all three seasons was in C. glomerata samples (53.55 ± 9.69 μg/100gDW). The lowest B12 vitamin concentration was in F. vesiculosus (4.14 ± 0.36 μg/100gDW). 16S RNA amplicon analysis revealed a correlation between Cyanobacteria and EPA, while no correlation could be found between B12 neither on phyla nor family levels. B12 content in the samples was in correlation with 5 potentially B12 synthesizing bacteria species (Rhodobacter capsulatus, Rhodobacter sphaeroides, Pseudomonas putida, Xanthomonas oligotrophicus and Aeromonas hydrophila) although the abundance of corresponding OTUs did not exceed 1 %.
... [4] Vitamin B12 deficiencies can cause anemia, autonomic neuropathy, cancers, cardiovascular diseases, cerebrovascular diseases, generalized weakness, loss of appetite, mental health issues, myalgia, and neural tube defects. [5] Most common causes of deficiency are due to either severe malabsorption by autoimmune gastritis, bowel diseases or gastrectomy, or by use of drugs that can cause malabsorption, and less dietary intake. [6] Several studies were done in the past to evaluate vitamin B12 levels in a wide range of populations like infants, pre-school children, school-aged children, pregnant and lactating women, women of reproductive age, adults, elderly, metformin treated individuals, vegetarians, lacto vegetarians, lacto-ovo vegetarians, non-vegetarians, active women (athletes), and sedentary women. ...
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Article
Purpose: To evaluate Vitamin B12 levels in healthcare professionals at a tertiary eyecare centre in India. Methods: This was a cross-sectional study conducted among healthcare professionals working at a tertiary eyecare centre in India. The sample included 2,374 employees. Chemiluminescent immunoassay method (reference range, 211-911 pg/ml) was used to assess serum vitamin B12 levels. Effect of age and gender was analyzed in vitamin B12 normal and vitamin B12 deficient groups. To evaluate risk factors, questions related to vitamin B12 deficiency were asked to the study participants in a survey. Results: The mean age of employees was 29.2 ± 0.7 years. Around 26% of them were vitamin B12 deficient. The proportion of males in the vitamin B12 deficient group (61.2%) was significantly higher (P < 0.0001) than that of the vitamin B12 normal group (44.9%). There was no effect of age on vitamin B12 levels in both vitamin B12 normal and vitamin B12 deficient groups. Mean vitamin B12 levels in males (289.1 ± 22.2 pg/ml) was significantly lower (P < 0.0001) than that of females (338.7 ± 30.0 pg/ml). Conclusion: This is the first such study on eyecare professionals. One-fourth of the eyecare professionals were vitamin B12 deficient. The proportion of males was higher in the vitamin B12 deficiency group. Males had lower vitamin B12 levels than females. Annual blood tests for vitamin B12 are recommended for timely diagnosis and management of vitamin B12 deficiency, particularly in males.
... Cobalamin (vitamin B 12 ) is a water-soluble vitamin that is abundant in foods of animal origin [144]. Vitamin B 12 can also be supplemented in foods in which it is not naturally synthesized. ...
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Article
Since Otto Warburg’s first report on the increased uptake of glucose and lactate release by cancer cells, dysregulated metabolism has been acknowledged as a hallmark of cancer that promotes proliferation and metastasis. Over the last century, studies have shown that cancer metabolism is complex, and by-products of glucose and glutamine catabolism induce a cascade of both pro- and antitumorigenic processes. Some vitamins, which have traditionally been praised for preventing and inhibiting the proliferation of cancer cells, have also been proven to cause cancer progression in a dose-dependent manner. Importantly, recent findings have shown that the nervous system is a key player in tumor growth and metastasis via perineural invasion and tumor innervation. However, the link between cancer–nerve crosstalk and tumor metabolism remains unclear. Here, we discuss the roles of relatively underappreciated metabolites in cancer–nerve crosstalk, including lactate, vitamins, and amino acids, and propose the investigation of nutrients in cancer–nerve crosstalk based on their tumorigenicity and neuroregulatory capabilities. Continued research into the metabolic regulation of cancer–nerve crosstalk will provide a more comprehensive understanding of tumor mechanisms and may lead to the identification of potential targets for future cancer therapies.
... Studies have reported that deficiency of B vitamins, including B12, induces genetic modification by adding uracil base instead of thymine resulting in chromosomal breaks, accordingly, high intake of vitamin B12 reduces the risk of TT-genotype colon cancer mutation [33]. Most studies conducted using vitamin B12 have proven that when it is used in combined therapy it contributes to increasing the effectiveness of anticancer drugs. ...
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Article
Background: 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is an effective anticancer agent, and when combined with other agents it shows superior activities. Vitamin B12 has been shown to contribute to increasing the effectiveness of anticancer drugs when used in combination. Thus, the current study aimed at investigating the anticancer potential of the combination of 1,25(OH)2D3 and vitamin B12. Methods: MTT assay was used to determine the cytotoxic activity of combining 1,25(OH)2D3 and vitamin B12 against six different cancer cell lines and one normal cell line. The surviving fraction after clonogenic assay was measured, and the effects of 1,25(OH)2D3/B12 combination on the activity of different caspases, cell adhesion, actin cytoskeleton, cell morphology, and percentage of polarized cells were evaluated. Results: Vitamin B12 did not cause cytotoxicity, however, it enhanced the cytotoxicity of 1,25(OH)2D3 against cancer cells. The cytotoxic effects of 1,25(OH)2D3 and its combination with vitamin B12 was not evident in the normal mammary MCF10A cell line indicating cancer cell-specificity. The cytotoxic effects of 1,25(OH)2D3/B12 combination occurred in a dose-dependent manner and was attributed to apoptosis induction which was mediated by caspase 4 and 8. Moreover, 1,25(OH)2D3/B12-treated cells showed enhanced inhibition of clonogenic tumor growth, reduced cell adhesion, reduced cell area, reduced percentage of cell polarization, and disorganized actin cytoskeleton resulting in reduced migratory phenotype when compared to cells treated with 1,25(OH)2D3 alone. Conclusion: 1,25(OH)2D3 and vitamin B12 exhibited synergistic anticancer effects against different cancer cell lines. The combination therapy of 1,25(OH)2D3 and vitamin B12 may provide a potential adjunctive treatment option for some cancer types.
... Deficiency of vitamin B12 can occur in different groups of people such as during growth in children and adolescents or in pregnancy 7 . It also leads to malfunctioning of the immunologic and hematologic parameter in the body 15 . Some people may have reduced intake, those with poor nutrition, age-old persons or people who adhere to a vegan die 6 . ...
Article
Vitamin B12 is the major dietary supplementary for most animals and has widespread applications in healthcare. The present study deals with the isolation of vitamin B12 producing strains from food waste soil samples. Three strains (VS1, VS2 and VS3) were isolated from the soil sample and the extraction was done using potassium ferrocyanide along with PBS buffer. Vitamin B12 was exhibited at about 114.1g/L from VS1 strains than the VS2 (11.4g/L) and VS3 (22.88g/L).
... Likewise, anemia might be an early sign of harmful disease, including myelodysplastic disorders (MDS). Finally, one third of aged anemic patients have unexplained anemia and no specific causes can be identified (12). ...
Article
Anticancer agents often cause bone marrow suppression resulting in progressive anemia which may influence the therapeutic effects of different cancer treatment. Objective: The objective of this study was to evaluate, effects of ethanolic extract of Saccharum munja roxb (Kaana or Sirkanda) on hemoglobin and red blood cells counts suppressed by carboplatin. Methodology: Anemia was induced in mice with a single iv dose of 50 mg/kg carboplatin. Hematological responses including, RBC and Hb was measured at 3rd, 5thand 8th day. Saccharum munja roxbethanolicextract with dose of 25mg/kg, 50mg/kg and 100mg/kg were given to different treatment groups. Results: In the low dose (R. ext 25mg/kg) group hemoglobin level was found to be 11g/dl on 8thday. However (R.ext 50mg/kg) showed more improvement in hemoglobin levels i.e11.5 g/dl at 8th day. The mice treated with higher doses of extract (R.ext100mg/kg) showed major improvement in hemoglobin levels at 8th day which was 12.6g/dl.RBC count increased after oral administration of Saccharummunja extract (R.ext 25mg/kg) to 6.4 ×106cells /mm3 on 8thday. However, in (R.ext 50mg/kg) extract treated group RBC count was found to be 6.9 × 106cells /mm3 on 8thday. In (R.ext 100mg/kg) treated group the RBC count was 7.4 × 106 /mm3 on 8thday. Conclusion: Thus, the results suggested that ethanolic-extract ofSaccharum munja roxb at different dosesshow beneficial effects in improving different parameters of blood.This study also appropriately described the time course of hematological changes after carboplatin induced anemia in mice. Therefore, this study method can be useful tool to explore potential strategies for the management of anemia caused by chemotherapeutic agents. Keywords: Carboplatin, heamoglobin, Saccharummunja
... Micronutrients, such as vitamin D, vitamin B12 and folic acid are essential for several important physiological functions (1)(2)(3)(4). Deficiencies of these vitamins are known to be associated with a wide range of disorders, affecting nearly every system in the human body (5)(6)(7)(8)(9)(10). In particular, the role of vitamin D (11)(12)(13), vitamin B12 and folic acid (14,15) in aging and late-life cognition is increasingly recognized in recent times. ...
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Article
Introduction: The important role of micronutrient deficiencies in aging-related disorders including dementia is becoming increasingly evident. However, information on their burden in India is scarce, especially, among aging and rural communities. Methods: Prevalence of vitamin D, B12 and folic acid deficiency was measured in an ongoing, aging cohort, from rural India–Srinivaspura Aging Neurosenescence and COGnition (SANSCOG) study cohort. Serum level estimation of vitamin D, B12 and folic acid, using chemiluminescence immunoassay, was performed on 1648 subjects (872 males, 776 females). Results: Mean vitamin D, B12 and folic acid levels were 23.4 ± 10.6 ng/ml, 277.4 ± 194.4 pg/ml and 6 ± 3.5 ng/ml), respectively. Prevalence of low vitamin D (<30 ng/ml), vitamin D deficiency (<20 ng/ml), B12 deficiency (<200 pg/ml) and folic acid deficiency (<3 ng/ml) were 75.7, 39.1, 42.3, and 11.1%, respectively. Significantly more women had vitamin D deficiency, whereas more men had folic acid deficiency. Women belonging to the oldest age group (≥75 years) had the maximum burden of low vitamin D (94.3%) and folic acid deficiency (21.8%). Discussion: Older, rural-dwelling Indians have high burden of vitamin D and B12 deficiencies, which is concerning given the potentially negative consequences on cognition, immunity and frailty in the aging population. Urgent public health strategies are needed to address this issue and prevent or mitigate adverse consequences.
... Lower levels of 25(OH) D have been found to be associated with increased risk of stress fractures in a number of military investigations [13] and Special Operations soldiers have reduced dietary quality, including reduced vitamin D intake when deployed [14]. Vitamin B 12 is essential for the synthesis of DNA, blood formation, and brain and nerve health [15,16]; deficiency can lead to hematological, neuropsychiatric, and cardiovascular disorders [17]. Based on data from the 1999 to 2002 National Health and Nutrition Examination Survey (NHANES), 3-6% of Americans were B 12 deficient while 14-20% had marginal B 12 depletion [18]. ...
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Article
Background This study examined incidence rates, temporal trends, and demographic factors associated with vitamin deficiencies/disorders in all United States military personnel from 1997 to 2015 (mean N = 1,382,266/year). Methods Employing an ecological study design, the Defense Medical Epidemiological Database and specific International Classification of Diseases codes were used to determine incidence rates for clinically-diagnosed vitamin deficiencies/disorders. Associations with demographic factors were examined. Results The overall incidence rate of vitamin deficiencies/disorders was 92.7 cases/100,000 person-years (p-yr). Highest rates were for vitamin D (53.7 cases/100,000 p-yr), other B-complex vitamins (20.2 cases, 100,000 p-yr), vitamin B 12 anemia (7.6 cases/100,000 p-yr), deficiencies of “other vitamins” (5.9 cases/100,000 p-yr), and vitamin A (2.5 cases/100,000 p-yr). Thiamin, riboflavin, niacin, pyridoxine, folate, vitamin C, and vitamin K deficiencies and hypervitaminoses A and D had < 1 case/100,000 p-yr. Rates for vitamin D, other B-complex, “other vitamin”, and thiamin deficiencies increased over time, while vitamin A and C deficiencies decreased. Women had higher incidence rates for all examined deficiencies/ disorders except niacin and vitamin C. Incidence rates rose with age in 8 of 15 deficiency/disorder categories and blacks had higher incidence rates in 9 of 15 deficiency/disorder categories. Conclusions The overall rate of clinically-diagnosed vitamin deficiencies and disorders was low but higher in women and minority subgroups. As for most illnesses, the diagnosed incidence of such disorders may be an underestimate of the actual incidence. These findings can guide clinical decision making with regard to testing for nutritional deficiencies and delivering public health information to at risk populations. Clinical trial registration (No. ISRCTN58987177 ). Registration date 9 October 2019.
... [36] Ryan-Harshman and Aldoori, 2008showed that the use of B12 vitamin leads to an increase in the quality of life in the individuals with nervous problems. [37] In the study by Moghadam et al. 2014 about the effect of fish oil supplements on the quality of life in the menopaused middle-aged women, the results indicated that fish oil supplement causes an improvement in the quality of the women's life. [30] As for the weight and BMI, the results of the present study indicated the reduction in these variables in both of the intervention and control groups; however, significant differences were observed only between the intervention group's body weights before and after the intervention. ...
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Article
BACKGROUND: Clinical trials concerning the effect of supplements or multivitamin on improving the quality of life have proven different results. The present study was conducted to examine the effect of multivitamin supplement on quality of life of the elderly. MATERIALS AND METHODS: Sixty-four old people over 65 years of age in Kermanshah Elderly Care Center participated in this randomized trial. The samples were first selected using the convenience sampling and then were randomly assigned into intervention and control groups. The intervention group received one multivitamin mineral (MVM) supplement capsule every day for 3 months with no intervention for the control group. Standard quality of life questionnaire was used to collect the data. Data were analyzed using the SPSS software version 22. RESULTS: The mean age of the participants was 70.77 ± 8.29 years. The results of intra-group evaluation of the aspects of quality of life of the elderly show the lack of significant changes in the mean scores of physical health and environmental health of the elderly in the intervention group (P > 0.05) and the significant reduction of these aspects in the control group (P < 0.05) after intervention. The mean score of mental health scores in the intervention group significantly increased (P = 0.01), but there are no significant changes in the control group (P = 0.273). The mean scores of social relationships as well as the overall score of quality of life in the intervention and control groups showed no significant changes (P > 0.05). CONCLUSION: The present study showed that the consumption of MVM supplements can have a positive effect on increasing the quality of life of the elderly, but it is recommended to be done in the long term along diet. Moreover, considering the fact that no change was observed in the other aspects of the quality of life, attentions should be paid to the environmental and social factors such as social supports and empowerment of the old people in the future studies.
... Apart from nutritional deficiency, inherited or acquired defects inhibit B12 absorption which enhance the vitamin B12 deficiency. These include parasitic and helicobacter pylori infection, tropical sprue, lack of intrinsic factor and malabsorption syndrome caused by gastrointestinal malfunction (5,31). ...
Article
Vitamin B12 is a water soluble micronutrient found in animal foods. Its deficiency is not uncommon in India owing to vegetarianism but often unrecognized due to diverse clinical manifestations. This review aims to collate the current data on vitamin B12 status in healthy Indian adult and elderly population. Online database Pubmed was searched for articles published in English between 2000 and 2019. Inclusion criteria consisted of original studies conducted on apparently healthy adult and elderly Indian population reporting serum/plasma vitamin B12 levels. Comprehensive literature search identified 14 studies eligible for inclusion. The deficiency prevalence reached 78.5% and 61.7% among adults and elderly, respectively, based on varying cut offs. Higher vitamin B12 levels were reported in women than men. Hyperhomocysteinemia (Hcy >15 μmol/L) was lower in females as compared to males (60% vs 90%, 14.9% vs 57.4% and 3.6% vs 20.9% respectively in three studies). Vitamin B12 deficiency was higher in vegetarians. The results indicate that inadequate vitamin B12 status is a wide spread problem in the Indian population. However, variety of laboratory methods and cut-offs of vitamin B12 deficiency and the heterogeneity in results pose challenges to draw clear conclusions on the extent of vitamin B12 deficiency in India. This review, therefore, highlights the need for more evidence based research to define age and sex specific cut offs for defining vitamin B12 deficiency.
... mg B12 per day accounted for a significant reduction in the risk of developing stroke [67]. Meanwhile, studies have proposed that hyperhomocysteinemia and cardiovascular risk in patients may precede the development of endstage renal disease (ESRD), chronic kidney disease (CKD) and dialysis [68][69][70]. Although CKD patients demonstrate an impairment in tissue uptake of B12 resulting in functional deficiency [71], the current evidence remains unclear to consider altered B12, folate and elevated tHcy levels as markers for CVD and cardiovascular mortality risk in ESRD and CKD individuals [72]. ...
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Article
Obesity is a worldwide epidemic responsible for 5% of global mortality. The risks of developing other key metabolic disorders like diabetes, hypertension and cardiovascular diseases (CVDs) are increased by obesity, causing a great public health concern. A series of epidemiological studies and animal models have demonstrated a relationship between the importance of vitamin B12 (B12) and various components of metabolic syndrome. High prevalence of low B12 levels has been shown in European (27%) and South Indian (32%) patients with type 2 diabetes (T2D). A longitudinal prospective study in pregnant women has shown that low B12 status could independently predict the development of T2D five years after delivery. Likewise, children born to mothers with low B12 levels may have excess fat accumulation which in turn can result in higher insulin resistance and risk of T2D and/or CVD in adulthood. However, the independent role of B12 on lipid metabolism, a key risk factor for cardiometabolic disorders, has not been explored to a larger extent. In this review, we provide evidence from pre-clinical and clinical studies on the role of low B12 status on lipid metabolism and insights on the possible epigenetic mechanisms including DNA methylation, micro-RNA and histone modifications. Although, there are only a few association studies of B12 on epigenetic mechanisms, novel approaches to understand the functional changes caused by these epigenetic markers are warranted.
... The degradation depends on specific parameters during the culinary process, e.g., temperature, oxygen, light, moisture, pH, and length of exposure [19]. Vitamin B12 is essential for DNA synthesis and for cellular energy production [60,61]. Vitamin B12 intake is obtained only through diet and in particular from meat products. ...
Article
This work explores the feasibility to apply supercritical CO 2 (SC−CO 2 ) drying alone or in combination with High-Power Ultrasounds (SC−CO 2 +HPU) to improve the shelf life and safety of raw chicken meat. SC−CO 2 +HPU drying process revealed the fastest water removal and higher rehydration capacity. A complete inactivation (6 log CFU/g) of mesophilic bacteria and yeasts and moulds was achieved with both the SC−CO 2 processes, while oven drying at 75 °C, used as control, showed only a limited inactivation (4 log CFU/g). The SC−CO 2 processes were efficient also for the inactivation of inoculated Salmonella. The retention of Vitamins B1, B2, B3 and B12 after the SC−CO 2 drying demonstrated the preservation of fresh like properties in terms of nutrients. Colour analysis showed a change in colour comparable to traditional cooking techniques. Results demonstrate that SC−CO 2 -based processes may be used as innovative technologies to dry chicken and make it microbiologically safe, while maintaining nutritional properties.
... More than 15 mmol/l of Hcy in blood is clinically hyperhomocysteinemia (Maron and Loscalzo, 2009). This condition, arising mostly due to deficiency in the cofactor vitamins along with genotype of the individual, is considered as a risk factor in various disease conditions, such as neural tube defects, cardio-vascular disorders and neuronal disorders (Refsum et al., 2004; Reynolds, 2006; Harshman and Aldoori, 2008; Selhub, 2008; Li et al., 2009; Greene et al., 2009). A better regime of B12 and folic acid is often helpful to counter the levels of hyperhomocysteinemia (hypHcy) (Bronstrup et al., 1998; Kluijtmans et al., 2003; Konstantinova et al., 2007). ...
... Our studies also suggest that migratory factors are secreted by PDMSC as the condition media collected from PDMSC cultures are rich in factors promoting migration. A recent study indicated that the placental MSCs secrete factors promoting migration, immune modulation and angiogenesis [28]. ...
Article
Micronutrient deficiency is well studied under many diseases. Angiogenesis, formation of new blood vessels is a break through interest of many researchers in diseases like cancer, diabetes. In this pilot study we aimed to comprehensively investigate the relationships of micronutrient deficiency and angiogenesis. We examined the results with the help of markers like VE-cadherin, VEGF, VWF, CD-31. Out of this study we conclude that micronutrient deficiency delays angiogenesis and weakens the existence of blood vessel.
... In addition, it has been associated with a number of health effects such as better fat digestion and visual acuity improvement in infants (26) . Vitamin B 12 can also be important in relation to both CVD and stroke through reduction of plasma homocysteine (27) . Mineral elements are among the most important nutrients provided by fish because they participate in many biological processes. ...
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Fish is an important source of energy, high-quality proteins, fat, vitamins and minerals. Within lipids, n -3 long-chain PUFA ( n -3 LC PUFA), mainly EPA and DHA, play an important role in health promotion and disease prevention. In contrast to the potential health benefits of dietary fish intake, certain chemical pollutants, namely heavy metals and some organic compounds, contained in seafood have emerged as an issue of concern, particularly for frequent fish consumers and sensitive groups of populations. The present review summarises the health benefits and risks of fish consumption. n -3 LC-PUFA are key compounds of cell membranes and play an important role in human health from conception through every stage of human development, maturation and ageing. DHA has a major role in the development of brain and retina during fetal development and the first 2 years of life and positively influences neurodevelopment, mainly visual acuity and cognitive functions. n -3 LC-PUFA are also effective in preventing cardiovascular events (mainly stroke and acute myocardial infarction) especially in persons with high cardiovascular risk. By contrast, there is convincing evidence of adverse neurological/neurodevelopmental outcomes in infants and young children associated with methylmercury exposure during fetal development due to maternal fish consumption during pregnancy. Dioxins and polychlorinated biphenyls present in contaminated fish may also develop a risk for both infants and adults. However, for major health outcomes among adults, the vast majority of epidemiological studies have proven that the benefits of fish intake exceed the potential risks with the exception of a few selected species in sensitive populations.
... The groups at higher risk for this deficiency are vegetarians and the elderly, with the deficiency rates reaching 20% for the latter. Deficient absorption is likely the main etiological factor in elderly individuals because intrinsic-factor deficiency, which is fundamental for the absorption of B12, is common in this age group [62]. ...
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An association between sulfur amino acids (methionine, cysteine, homocysteine and taurine) and lipid metabolism has been described in several experimental and population-based studies. Changes in the metabolism of these amino acids influence serum lipoprotein concentrations, although the underlying mechanisms are still poorly understood. However, recent evidence has suggested that the enzyme stearoyl-CoA desaturase-1 (SCD-1) may be the link between these two metabolic pathways. SCD-1 is a key enzyme for the synthesis of monounsaturated fatty acids. Its main substrates C16:0 and C18:0 and products palmitoleic acid (C16:1) and oleic acid (C18:1) are the most abundant fatty acids in triglycerides, cholesterol esters and membrane phospholipids. A significant suppression of SCD-1 has been observed in several animal models with disrupted sulfur amino acid metabolism, and the activity of SCD-1 is also associated with the levels of these amino acids in humans. This enzyme also appears to be involved in the etiology of metabolic syndromes because its suppression results in decreased fat deposits (regardless of food intake), improved insulin sensitivity and higher basal energy expenditure. Interestingly, this anti-obesogenic phenotype has also been described in humans and animals with sulfur amino acid disorders, which is consistent with the hypothesis that SCD-1 activity is influenced by these amino acids, in particularly cysteine, which is a strong and independent predictor of SCD-1 activity and fat storage. In this narrative review, we discuss the evidence linking sulfur amino acids, SCD-1 and lipid metabolism.
... In elderly individuals, mild to moderate deficiency of B12 can be found in 20% of the population due to malabsorption because of gastrointestinal problems [82]. Elderly deficient in B12 may also present with impaired cognition [85]. The U.S. RDA is 2.4 μg per day for adults 50 years or above [53]. ...
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Because of ongoing global ageing, there is a rapid worldwide increase in incidence of osteoporotic fractures and the resultant morbidity and mortality associated with these fractures are expected to create a substantial economic burden. Dietary modification is one effective approach for prevention of osteoporosis in the general population. Recently, B vitamins have been investigated for their possible roles in bone health in human studies. In this review, we provide different lines of evidence and potential mechanisms of individual B vitamin in influencing bone structure, bone quality, bone mass and fracture risk from published peer-reviewed articles. These data support a possible protective role of B vitamins, particularly, B2, B6, folate and B12, in bone health. However, results from the clinical trials have not been promising in supporting the efficacy of B vitamin supplementation in fracture reduction. Future research should continue to investigate the underlying mechanistic pathways and consider interventional studies using dietary regimens with vitamin B enriched foods to avoid potential adverse effects of high-dose vitamin B supplementation. In addition, observational and interventional studies conducted in Asia are limited and thus require more attention due to a steep rise of osteoporosis and hip fracture incidence projected in this part of the world.
... Pernicious anemia is the most common cause of cobalamin deficiency worldwide [1]. However, among elderly population, food-cobalamin malabsorption which is caused by gradual atrophy of gastric mucosa and hypochlorhydria is responsible for the majority of cases [2,3,6]. The syndrome is characterized by the inability to release cobalamin from food for absorption due to reduced gastric acid secretion, but unbound cobalamin can be absorbed normally [2,3]. ...
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A 52-year-old male with no significant past medical history reports increasing generalized fatigue and weakness for the past 2 weeks. Physical examination reveals jaundice and pallor without organomegaly or lymphadenopathy. His hemoglobin was 5.9 g/dL with a mean corpuscular volume of 87.1 fL and elevated red blood cell distribution width of 30.7%. His liver function test was normal except for elevated total bilirubin of 3.7 mg/dL. Serum LDH was 701 IU/L, and serum haptoglobin was undetectable. Further investigation revealed serum vitamin B12 of <30 pg/mL with elevated methylmalonic acid and homocysteine level. In addition, serum ferritin and transferrin saturation were low. The patient was diagnosed with hemolytic anemia secondary to vitamin B12 deficiency with concomitant iron deficiency anemia.
... High plasma levels of Hcy have been demonstrated to be a risk factor in various disease conditions, including neural tube defects, cardiovascular and neural disorders [5,6]. In particular, HyHcy has been demonstrated to be an independent risk factor for cardiovascular-related mortality and patients with lower plasma levels of 12 lmol/l Hcy presented higher survival rates after an acute coronary syndrome [7,8]. ...
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To assess the possible role of hyperhomocysteinemia (HyHcy) in delaying recovery after acute vestibular neuritis. In our retrospective study, 90 subjects were evaluated within 7 days from the beginning of an acute vertigo. All subjects had high plasma levels of homocysteine (Hcy). 46 patients were treated with homocysteine lowering therapy and betahistine for 1 month, while 44 subjects received only betahistine. Subjective symptoms were evaluated with the Dizziness Handicap Inventory (DHI) questionnaire, administered 7 days after the beginning of vertigo and again after 1 month. Moreover, postural control performed at 1 month’ control was studied with static stabilometry in a subgroup of 21 non-treated and 20 treated patients. DHI total score decreased significantly more in the subgroup of subjects treated with homocysteine lowering therapy. Moreover, posturographic data were significantly increased in non-treated compared with treated subjects. Our data support the possibility of a role of HyHcy in preventing recovery after a recent vestibular neuritis. A microvascular disorder or the neurotoxic effect of HyHcy have been considered as possible causal factors. Although not conclusive, our data are not inconsistent with the hypothesis of a poorer adaptation in patients with untreated HyHcy.
... However more research, particularly in the area of nutritional genomics, is needed to determine how vitamin B 12 might augment the benefits of folic acid. So foods have to be fortified with vitamin B 12 in addition to the current mandatory folic acid fortification of grains [53]. ...
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According to the World Health Organization the term congenital anomaly includes any morphological, functional, biochemical or molecular defects that may develop in the embryo and fetus from conception until birth, present at birth, whether detected at that time or not. Based on World Health Organization report, about 3 million fetuses and infants are born each year with major malformations. Several large population based studies place the incidence of major malformations at about 2–3% of all live births. In this study we tried to assess the frequency and nature of congenital malformations (CMs) among Egyptian infants and children as well as the associated maternal, paternal and neonatal risk factors. Patients (13,543) having CMs were detected among 660,280 child aged 0–18years attending the Pediatric Hospital Ain Shams University during the period of the study (1995–2009), constituting 20/1000. Males were more affected than females (1.8:1). According to ICD-10 classification of congenital malformations the commonest system involved were, nervous system, followed by chromosomal abnormalities, genital organs, urinary system, musculoskeletal, circulatory system, eye, ear, face, and neck, other congenital anomalies, digestive system, cleft lip and palate, and respiratory anomalies. Among the maternal risk factors detected were multiparity, age of the mother at conception, maternal illness, exposure to pollutants, and intake of the drugs in first months. Consanguineous marriage was detected in 45.8% of patients. Surveys of CMs must be done in every country to provide prevalence, pattern of occurrence, nature, identify causes, and associated risk factors to prevent or reduce the occurrence of CMs.
... There has been little research to our knowledge on whether nutritional deficits are a cause of the adverse obstetric outcomes in women with SMI. However, there is now a growing evidence base that reports nutritional deficiencies associated with schizophrenia, depression and bipolar disorder, including single nutrient deficiencies such as folate, omega 3, vitamin B 12 , iron and zinc (Taylor et al. 2003;Taylor and Geddes 2004;Freeman et al. 2006;Ryan-Harshman and Aldoori 2008;DiGirolamo and Ramirez-Zea 2009;Goff et al. 2004). We therefore aimed to carry out a systematic review to investigate whether pregnant women and childbearing aged women with severe mental illness have a significantly greater risk of nutritional deficiencies compared with pregnant women and childbearing aged women with no mental illness. ...
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Little is known about the nutritional status of pregnant women with severe mental illness. We therefore carried out a systematic review to investigate whether pregnant women and childbearing aged women with severe mental illness have significantly greater nutritional deficiencies compared with pregnant women and childbearing aged women with no mental illness. We carried out a search using MEDLINE, EMBASE and PsycINFO from January 1980 to January 2011 for studies on nutritional status of childbearing aged women with psychotic disorders. Identification of papers and quality rating of papers (using a modified version of the Newcastle-Ottawa scale) was carried out by two reviewers independently. We identified and screened 4,130 potentially relevant studies from the electronic databases. Fifteen studies met the inclusion criteria (n = 587 women). There were no studies of pregnant women. There was some evidence of low serum folate and vitamin B(12) levels and elevated homocysteine levels in childbearing aged women with psychotic disorders. Further research into the nutritional status of childbearing aged women with severe mental illness is needed. Maternal nutrition has a profound impact on foetal outcome, is a modifiable risk factor and therefore needs prioritising in the care of all childbearing aged women with severe mental illness.
... In this regard, the low genetic and shared environmental effects—and very high non-shared environmental effect—for vitamin intake are particularly promising. Like minerals, vitamins play an important role in biological processes and have been shown to hold important implications in a wide range of conditions , such as neurocognitive deficits in children (Liu et al. 2003) and behavior problems across childhood (Liu et al. 2004; Liu and Raine 2006), as well as chronic diseases, including multiple sclerosis (Hayes 2000), cancer (Guyton et al. 2001), osteoarthritis (McAlindon et al. 1996 ), cardiovascular disease (Harshman and Aldoori 2008), and cognitive impairment and dementias (Selhub et al. 2010). The emerging focus on nutritional genomics and genetics has provided increasing evidence for the importance of micronutrients in genome stability and health. ...
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The relationship between genetic and the environment represents a pathway to better understand individual variations in nutrition intake and food preferences. However, the present literature is weakened somewhat by methodological flaws (e.g., overreliance on self-report questionnaires), discrepancies in statistical approaches, and inconsistent findings. Little research on this topic to date has included examination of micronutrient intake. The purpose of this study is to improve the existing literature on genetic and environmental influences on energy and nutrient intake by addressing these gaps. Twin pairs (N = 358; age 11-13 years) provided 3-day food intake diaries, which were assessed for intake of total energy, macronutrients, and micronutrients. Structural equation modeling revealed that genetic influences accounted for a significant portion of the total variance in total energy (48 %), macronutrients (35-45 %), minerals (45 %), and vitamins (21 %). Consistent with previous studies, the shared environment appeared to contribute little to nutritional intake. Findings on vitamin and mineral intake are novel and are particularly beneficial for further research on the contribution of micronutrients to individual physical health status. Better understanding of the linkage between genes, environment, and nutritional intake and deficiencies can clarify behavioral and physical outcomes, potentially informing risk reduction, primary prevention, and intervention strategies.
... Vitamin B 12 plays a key role in the normal function of the nervous system and in erythropoiesis 56 , is involved in the cellular metabolism affecting DNA synthesis and regulation 57 , and also plays an important role in fatty acid synthesis and energy production 58 . Since vitamin B 12 is found exclusively in animal products, vegetarians consuming eggs, cheese, milk or yoghurt receive an adequate supply of this vitamin. ...
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In dieser Rubrik werden „Position-Statements“ renommierter nationaler und internationaler Fachgesellschaften publiziert. Diesmal präsentieren wir Ihnen eine Publikation der FIMS (Fédération Internationale de Médecine du Sport - International Federation of Sports Medicine) - www.fims.org A balanced intake of macro- and micro nutrients is crucially important for conditioning, recovery from fatigue after exercise, as well as for injury prevention. An increasing number of athletes have adopted vegetarian diets for one or more reasons and actually there is no available evidence to support either a beneficial or a detrimental effect of a vegetarian diet on sport performance. Therefore, it is widely accepted that appropriately planned vegetarian diets can provide sufficient nutrient energy with an appropriate range of carbohydrate, fat, and protein intake to support performance and health. On the other hand, questions have been raised by some investigators regarding unique risks of the vegetarian diet, including oligomenorrhea and amenorrhea, iron deficiency, vitamin B12 deficiency, vitamin D deficiency, and impaired mineral status. In the present overview those items are described with the aim of identifying intervention warnings for vegetarian athletes.
... Vitamin B12 deficiency is associated with hematologic and neuropsychiatric manifestations, including macrocytic (megaloblastic) anemia, paresthesias, peripheral neuropathy, impaired memory, irritability, depression and dementia 3 . Recent studies found an association between B12 deficiency and increasing risk of cardiovascular disease (CVD) 4,5 cancer 6,7 , mental health problem 8 , osteoporosis 9 , and defect-birth outcomes 10 . It has also been suggested that adequate levels of B12 have a protective effect against chronic disease and neural tube defect 11 . ...
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Vitamin B12 (B12) is essential for well-being and healthy life, since it plays a critical role in DNA synthesis, hematopoiesis and neurologic function. B12 deficiency remains one of the most common nutrition deficiencies in the world and is associated with increasing risk of cardiovascular disease, cancer, mental health problem, osteoporosis, and defect-birth outcomes. The main objective of this study is to determine the impact of B12 levels on quality of life (QOL) among healthy university students. This cross-sectional study involved 359 healthy university students (age 18-30 years) of both genders. Their QOL was as vitamin B12 level was measured using the IMx system (Abbott laboratories IMX, USA). Results: No correlation was detected between B12 levels and the two major QOL subscales: the Physical Component Summary (PCS) and Mental Component Summary (MCS). Additionally, none of the other eight subscale of the SF-36 was significantly correlated with b12 levels. We conclude that no correlation exists between B12 levels and QOL scores among young adult healthy populations. Further investigations are required to confirm the impact of B12 status on QOL among healthy populations.
... More than 15 mmol/l of Hcy in blood is clinically hyperhomocysteinemia (Maron and Loscalzo, 2009). This condition, arising mostly due to deficiency in the cofactor vitamins along with genotype of the individual, is considered as a risk factor in various disease conditions, such as neural tube defects, cardio-vascular disorders and neuronal disorders (Refsum et al., 2004;Reynolds, 2006;Harshman and Aldoori, 2008;Selhub, 2008;Li et al., 2009;Greene et al., 2009). A better regime of B12 and folic acid is often helpful to counter the levels of hyperhomocysteinemia (hypHcy) (Bronstrup et al., 1998;Kluijtmans et al., 2003;Konstantinova et al., 2007). ...
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Unlike most Western populations, MTHFR 677T is a rare allele and a risk factor for a variety of disorders in India. What kind of nutritional (environmental) and/or genetic factors could contribute to the genetic risk is not known. To assess the incidence of hyperhomocysteinemia and its correlation with the polymorphism in homocysteine (Hcy)-pathway genes and associated cofactors in the native populations of eastern India. Healthy population from four eastern states of India. Genotyping of SNPs, HPLC and chemiluminescence-based assay for homocysteine, vitamin B12 and folic acid. Approximately 30% of the population has hyperhomocysteinemia (>15 μmol/lit; hypHcy) with varying frequencies in the four states from where samples were collected (n=1426). Polymorphisms of MTR and CBS do not affect hypHcy. 677T and 1298C alleles of MTHFR and G80 RFC-1 show association with hypHcy. In contrast, RFC-1 80AA is protective even in presence of 677T MTHFR. Addition of each mutant allele has an additive effect on Hcy level. Vitamin B12 (cofactor in methionine synthesis) clearly modulates the genotypic effect on Hcy level. Although frequency of individuals with low folic acid is ≈11, 49% of the population is vitamin B12 deficient (<220 pg/lit) and has a significant negative correlation with Hcy. Individuals with optimum vitamin B12 and folic acid generally have low Hcy, even in risk genotypes. One of the plausible reasons for susceptibility of individuals with MTHFR C677T in the studied population to various disorders is the high frequency of hyperhomocysteinemia and vitamin B12 deficiency in the 'healthy population'. Apparently, supplementation of vitamin B(12) to this health-impoverished community may help lessen the risk of several multifactorial disorders.
... Lastly, other researchers using this data set to explore relationships of vitamin B12 status and health should consider limiting their analyses to the subset of participants who did not report receiving vitamin B12 injections. [78] 92.2 ± 69.5 [208] < 10 (severe atrophic gastritis) 7.7 [6] 5.8 [12] 10 to < 60 (moderate atrophic gastritis) 19.2 [15] 29.8 [62] ≥ 60 (atrophic gastritis not present) 73.1 [57] 64.4 [134] Creatinine [20] 50.2 *** [106] Mean cell volume (fl) 91, 74–103 92, 71–135 91.3 ± 5.1 [79] 91.7 ± 6.5 [211] ≥ 100 (macrocytosis) 1.3 [1] 3.3 [7] a Participants receiving vitamin B12 injections were excluded. Differences between octogenarians and centenarians that were statistically significant are noted as follows: ...
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Test the hypotheses that vitamin B12 deficiency would be prevalent in octogenarians and centenarians and associated with age, gender, race/ethnicity, living arrangements (community or skilled nursing facility), animal food intake, B-vitamin supplement use, atrophic gastritis, folate status, and hematological indicators. Population-based multi-ethnic sample of adults aged 80 to 89 and 98 and above. Northern Georgia in the United States. Men and women aged 80 to 89 (octogenarians, n = 80) and 98 and older (centenarians, n = 231). Wilcoxon signed-rank tests, Fisher's exact tests, and logistic regression analysis was used to examine the associations of vitamin B12 status with the variables of interest. After excluding participants receiving vitamin B12 injections (n = 17), the prevalence of vitamin B12 deficiency was higher in centenarians than in octogenarians (35.3% vs. 22.8%, p < 0.05, defined as plasma vitamin B12 < 258 pmol/L and serum methylmalonic acid > 271 nmol/L and methylmalonic acid > serum 2-methylcitrate) and in both age groups was correlated with significantly higher homocysteine (p < 0.05) and lower plasma and red cell folate (p < 0.01), but was not related to hemoglobin, anemia, mean cell volume, or macrocytosis. In logistic regression analysis, the probability of being vitamin B12-deficient was significantly increased by being a centenarian vs. octogenarian (p < 0.03), by being white vs. African American (p < 0.02), by increasing severity of atrophic gastritis (p < 0.001), and by not taking oral B-vitamin supplements (p < 0.01), but was not related to gender, living arrangements, or animal food intake. Centenarians and octogenarians are at high risk for vitamin B12 deficiency for many of the same reasons identified in other older adult populations. Given the numerous potential adverse consequences of poor vitamin B12 status, efforts are needed to ensure vitamin B12 adequacy in these older adults.
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Alzheimer's disease is a degenerative neurologic condition for which there is no known cure. Between 2002 and 2019, 99.6% of all drug candidates tried failed in achieving the goal of preventing or treating the development of Alzheimer's disease. In view of the fact that many of the current FDA approved pharmacologic agents utilized in the treatment of Alzheimer's disease are directly derived from plants, a resurgence in research is underway to find phytochemicals capable of preventing and treating this devastating disease. Phytochemicals such as curcumin, saffron and lemon balm have efficacy in preventing and mitigating disease progression in Alzheimer's dementia.
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Vitamins are micronutrients which form an essential part of our diet. They are needed for healthy functioning of metabolic activities, some forms of vitamin form basis for our immunity and bone building. Usually essential nutrients cannot be synthesised in our bodies, hence we need to obtain them from our diet. Many Vitamin groups have been studied extensively for the pharmacological effects. Many studies have proved the effectiveness of combination therapies of vitamins with other medication for treatment of various diseases. This review presents all the studies conducted to prove the therapeutic effects of vitamins. Keywords: Multivitamins, Vitamin A, Vitamin B, Vitamin C, Vitamin D, Ginseng, Niacinamide, Antibiotics, Cefuroxime, DAV Therapy.
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Food analysis has been gaining interest throughout recent decades for different reasons: the detection of hazardous substances in food and routine investigations of food composition and vitamin/nutrient contents. Regardless of the targeted component, food analysis raises a few challenges regarding the complexity of the matrix and detecting trace amounts of substances. We report herein the results obtained regarding the simultaneous detection of two B vitamins (riboflavin, vitamin B2 and cyanocobalamin, vitamin B12) by means of SERS. SERS provides molecular fingerprint identification and high analytical sensitivity together with a low processing time and cost. All these make SERS a promising tool for the development of food analytical methods.
Chapter
C’est en 1911 qu’un chimiste du nom de Casimir Funck isola à partir du son de riz une substance cristallisée possédant une fonction amin. Cette substance se révéla capable de prévenir et de guérir le béribéri expérimental et Funk créa le terme de vitamine afin de souligner que cette amine était indispensable à la vie. Il a fallu cinquante ans à la communauté scientifique pour caractériser, puis pour isoler et synthétiser les treize substances, neuf de nature hydrosoluble et quatre de nature liposoluble, qui constituent la série des vitamines (tableaux I et II) (1).
Article
Objective: Vitamin B12 (VB12) and folic acid (FA) deficiencies may be subtle and unrecognized and cause various neuropsychiatric problems. Serum levels of VB12, FA and distribution patterns in a broad range of hospital adult population were investigated. Methods: Cross-sectional analysis of laboratory results of VB12, FA during a year was made in a university hospital. Only the first measurements of the patients during this time frame were taken into analysis. The patients under 18 years were excluded. The laboratory results of 13875 patients VB12, FA levels were analysed. The mean levels of VB12, FA were analysed. VB12 and FA levels in different age groups and gender were also studied. Three different levels of VB12 were also analysed. Results: The overall mean level of VB12 (n=13875) and FA were 344.84 ± 184.44 pg/mL, and 8.76 ± 3.96 ng/mL respectively. Mean levels of VB12 were 350.77 ± 184.43 pg/mL, in females and 332.20 ± 183.84 pg/mL, in males whereas mean FA levels were 9.12 ± 3.99 ng/mL in females and 8.01± 3.78 ng/mL in males. VB12 and FA levels was significantly high in females (p<0.001). Level of VB12 was significantly different in all age groups (p: 0.0001). Conclusions: We believe that VB12 and FA deficiency should be considered in a primary care setting and it is easy to treat and prevents serious neurological and psychiatric complications.
Chapter
In relation to the genome, investigation of the epigenome is emerging as an equal, if not more influential factor in modulating human health and disease. Since epigenetic modifications are gradual in onset and potentially reversible, determining factors that modulate the epigenome is critical for possible preventive and therapeutic interventions. The development and progression of cancer is mechanistically linked to a number of epigenetic changes, including global DNA hypomethylation and gene-specific CpG promoter DNA hypermethylation. Environmental factors, including diet, have been shown to affect cancer risk, via epigenetic and non-epigenetic mechanisms. In this regard, one-carbon nutrients are prototypic dietary factors that may modulate cancer risk via epigenetic mechanisms. This chapter will discuss the role of nutrients involved in one-carbon metabolism and their effect on cancer risk via epigenetic modifications with a particular focus on DNA methylation. © 2014 Springer Science+Business Media New York. All rights are reserved.
Article
Vitamin B12 deficiency is occurring in younger adults at rates that parallel that of the elderly. This study evaluated the efficacy of vitamin B12 supplementation through either cereal (> 4 serv/wk 100% DV) or B12 supplement (1000 mcg/d) in 137 women identified at time of annual exam as having low-normal plasma B12 level (200-250 pg/ml). Significant (p < 0.05) increases in mean plasma vitamin B12 was observed in all subjects after 3 months of either type of supplementation. Subjects whose baseline B12 status was < 200 pg/ml did not increase B12 levels to the 250 pg/ml benchmark. Nurse practitioners are positioned to effectively prevent the risk of vitamin B12 deficiency in younger adult patients.
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There is a considerable body of literature suggesting a wide range of health benefits associated with diets high in seafood. However, the demand for seafood across the world now exceeds that available from capture fisheries. This has created a rapidly increasing market for aquaculture products, the nutrient composition of which is dependent on feed composition. The use of fishmeal in this food chain does little to counteract the environmental impact of fisheries and so the on-going development of alternative sources is to be welcomed. Nevertheless, an in-depth understanding as to which nutrients in seafood provide benefit is required to permit the production of foods of maximal health benefit to humans. This paper reviews our current knowledge of the beneficial nutrient composition of seafood, in particular omega-3 fatty acids, selenium, taurine, vitamins D and B12, in the context of the development of environmentally sustainable aquaculture.
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Vitamin B12 deficiency is a common cause of neuropsychiatric symptoms in elderly persons. Malabsorption accounts for the majority of cases. Vitamin B12 deficiency has been associated with neurologic, cognitive, psychotic, and mood symptoms, as well as treatment-resistance. Clinician awareness should be raised to accurately diagnose and treat early deficiencies to prevent irreversible structural brain damage, because current practice can be ineffective at identifying cases leading to neuropsychiatric sequelae. This clinical review focuses on important aspects of the recognition and treatment of vitamin B12 deficiency and neuropsychiatric manifestations of this preventable illness in elderly patients.
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The European Micronutrient Recommendations Aligned (EURRECA) Network aims to provide standardized approaches to reveal and beneficially influence variability within the European Union in micronutrient recommendations for vulnerable population groups. Characterization of the 'vulnerability' together with the 'variability' of micronutrient needs represents the first step to creating guidelines for setting micronutrient recommendations within target populations. This paper describes some of the key factors and characteristics relevant to assess micronutrient requirements and formulate recommendations of micronutrients in pregnancy. Nutritional requirements during pregnancy increase to support fetal growth and development as well as maternal metabolism and tissue accretion. Micronutrients are involved in both embryonal and fetal organ development and overall pregnancy outcomes. Several factors may affect directly or indirectly fetal nourishment and the overall pregnancy outcomes, such as the quality of diet including intakes and bioavailability of micronutrients, maternal age, and the overall environment. The bioavailability of micronutrients during pregnancy varies depending on specific metabolic mechanisms because pregnancy is an anabolic and dynamic state orchestrated via hormones acting for both redirection of nutrients to highly specialized maternal tissues and transfer of nutrients to the developing fetus. The timing of prenatal intakes or supplementations of specific micronutrients is also crucial as pregnancy is characterized by different stages that represent a continuum, up to lactation and beyond. Consequently, nutrition during pregnancy might have long-lasting effects on the well-being of the mother and the fetus, and may further influence the health of the baby at a later age.
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BluB is a distinct flavin destructase that catalyzes a complex oxygen-dependent conversion of reduced flavin mononucleotide (FMNH(2)) to form 5,6-dimethylbenzimidazole (DMB), the lower ligand of vitamin B(12). The catalyzed mechanism remains a challenge due to the discrepancy between the complexity of the conversion and the relative simplicity of the active site of BluB. In this study, we have explored the detailed conversion mechanism by using the hybrid density functional method B3LYP on an active site model of BluB consisting of 144 atoms. The results indicate that the conversion involves more than 14 sequential steps in two distinct stages. In the first stage, BluB catalyzes the incorporation of dioxygen, and the fragmentation of the isoalloxazine ring of FMNH(2) to form alloxan and the ribityl dimethylphenylenediimine (DMPDI); in the second stage, BluB exploits alloxan as a multifunctional cofactor, such as a proton donor, a proton acceptor, and a hydride acceptor, to catalyze the remaining no fewer than 10 steps of the reaction. The retro-aldol cleavage of the C1'-C2' bond of DMPDI is the rate-determining step with a barrier of about 21.6 kcal/mol, which produces D-erythrose 4-phosphate (E4P) and the ring-closing precursor of DMB. The highly conserved residue Asp32 plays critical roles in multiple steps of the conversion by serving as a proton acceptor or a proton shuttle, and another conserved residue Ser167 plays its catalytic role mainly in the rate-determining step by stabilizing the protonated retro-aldol precursor. These results are consistent with the available experimental observations. More significantly, the novel intermediate-assisted mechanism not only provides significant insights into understanding the mechanism underlying the power of the simple BluB catalyzing the complex conversion of FMNH(2) to DMB, but also represents a new type of intermediate-assisted multifunctional catalysis in an enzymatic reaction.
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Introducción. Se han establecido relaciones entre la deficiencia de micronutrientes y un riesgo significativamente alto de problemas reproductivos, desde infertilidad hasta defectos estructurales en el feto y enfermedades a largo plazo. En esta revisión, nos concentramos en los riesgos reproductivos relacionados con la ingesta de determinados micronutrientes durante el período periconcepcional, un momento clave para determinar el desarrollo y la salud del feto, ya que es la etapa en la que pueden iniciarse diversos trastornos. Métodos. Se realizaron búsquedas en las bases de datos Embase, Medline y PubMed, en bibliografía científica indexada en Google y en los periódicos de la biblioteca en línea de la Universidad de Milán, a fin de identificar publicaciones relevantes. La búsqueda se orientó principalmente a estudios in vivo sobre humanos pero, cuando fue necesario, también se tuvieron en cuenta estudios sobre animales y experimentos in vitro y de cultivos celulares. Resultados. Las etapas clave que podrían resultar afectadas por los nutrientes incorporados durante el período periconcepcional son la fertilidad, la concepción, la implantación, la organogénesis fetal y la placentación. Estos mecanismos son influidos por las concentraciones de especies reactivas de oxígeno (ERO) y de homocisteína total (tHcy) en plasma. El período preconcepcional es de particular importancia, ya que afecta tanto la fertilidad como las primeras etapas de la gestación. La ingesta de macronutrientes en la dieta y el estado de salud materno afectan las diferentes fases del inicio y el desarrollo del embarazo, así como del embrión. Conclusión. Si bien se han realizado pocos estudios sobre humanos, y solamente se han obtenido pruebas concluyentes respecto del consumo periconcepcional de folato y la prevención de defectos del tubo neural (DTN), los datos encontrados indican que los micronutrientes pueden afectar la fertilidad, la embriogénesis y la placentación y que el uso profiláctico de algunos micronutrientes puede ser útil para prevenir diversas complicaciones durante el embarazo. Sería recomendable generar conciencia sobre la necesidad de una dieta saludable, no sólo durante el embarazo, sino también antes. Sin embargo, se necesitan más estudios sobre humanos para determinar con exactitud los requerimientos de micronutrientes durante el período periconcepcional.
Article
Micronutrient deficiencies have been associated with significantly high reproductive risks, ranging from infertility to fetal structural defects and long-term diseases. In this review we focus on the reproductive risks related to some micronutrients during the periconceptional period, a critical step in determining fetal development and health due to the potential onset of several disorders. Embase Medline and PubMed databases, Google-indexed scientific literature and periodics from on-line University of Milan Bibliotecary Service were searched to identify relevant publications. In vivo human studies were mainly searched for, but when needed animal studies as well as in vitro and cell culture experiments were also considered. Fertility, conception, implantation, fetal organogenesis and placentation are the critical stages potentially affected by nutrition during the periconceptional period. Reactive oxygen species (ROS) and total homocysteine (tHcy) plasma levels are factors involved in the respective mechanisms. The preconceptional period is particularly important since it affects both fertility and the early stages of gestation. Micronutrients' dietary intake and maternal status affect the different phases of the onset and development of pregnancy as well as of the conceptus. Although human studies are scarce, and conclusive evidence is provided solely for periconceptional folate and prevention of neural tube defects (NTDs), the overall data indicate that micronutrients may affects fertility, embryogenesis and placentation, and the prophylactic use of some micronutrients may be useful in preventing several adverse pregnancy outcomes. Efforts to increase awareness of a healthy diet should be strengthened not only throughout pregnancy but also before. However, further researches in humans are necessary to optimise periconceptional micronutrient requirements.
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To investigate, in an elderly population: (1) the effects of oral B-vitamin therapy on P-tHcys, S-MMA and Hb/MCV, (2) the appropriate decision limit for 'high' metabolite concentrations and (3) the estimated prevalence of vitamin B(12)/folate deficiency on the basis of different decision limits. Double-blind placebo-controlled intervention study. Outpatient clinic. A total of 209 community-dwelling subjects, median age 76 y (range 70-93) y. Four months of oral daily supplementation with 0.5 mg cyanocobalamin, 0.8 mg folic acid and 3 mg vitamin B(6). High P- tHcys was found in 64% of men and 45% of women, high S-MMA in 11% of both. Vitamin B(12) deficiency was observed in 7.2% and folate deficiency in 11% of all subjects. Health-related upper reference limits for the metabolites at the start were higher than the laboratory's upper reference limits. The latter were, however, similar to those of the vitamin replete group. There was a significant decrease in P-tHcys (P<0.001) and S-MMA (P=0.009) after 4 months of vitamin treatment. In a multivariate analysis, the P-Hcys change correlated positively with baseline P-tHcys and inversely with baseline P-folate and transferrin saturation (Fe/TIBC ratio). The S-MMA change correlated with baseline S-MMA and inversely with baseline vitamin B(12) and age. Suboptimal vitamin status is an important cause of elevated P-tHcys and S-MMA in apparently healthy elderly subjects. Oral B-vitamin therapy is an effective and convenient way to normalise P-tHcys and S-MMA.
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Increased folate intake reduces the risk of neural tube defects, other malformations and also possibly, pregnancy complications. Increasing evidence suggests that the beneficial effect of folate may be related to improved function of methionine synthase, a vitamin B12-dependent enzyme that converts homocysteine to methionine. In India, the majority of the population adheres to a vegetarian diet known to be deficient in vitamin B12. In such a population, increased folate intake may offer minimal protection against birth defects, whereas vitamin B12 administration should be considered. In this review, is described the metabolism of and interrelations between folate, vitamin B12 and homocysteine. This is followed by a brief discussion of some of the proposed mechanisms for their biological effects in relation to birth defects and pregnancy outcome.
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Fortification of food with folic acid to prevent neural-tube defects in babies also lowers plasma total homocysteine, which is a risk factor for vascular disease. We investigated the effect of folate and vitamin B12 on homocysteine concentrations. 30 men and 23 women received sequential supplementation with increasing doses of folic acid. After supplementation, the usual dependency of homocysteine on folate diminished, and vitamin B12 became the main determinant of plasma homocysteine concentration. This finding suggests that a fortification policy based on folic acid and vitamin B12, rather than folic acid alone, is likely to be much more effective at lowering of homocysteine concentrations, with potential benefits for reduction of risk of vascular disease.
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The associations of vitamin B(12), folate, and homocysteine with depression were examined in a population-based study. The authors screened 3,884 elderly people for depressive symptoms. Subjects with positive screening results had psychiatric workups. Folate, vitamin B(12), and homocysteine blood levels were compared in 278 persons with depressive symptoms, including 112 with depressive disorders, and 416 randomly selected reference subjects. Adjustments were made for age, gender, cardiovascular disease, and functional disability. Hyperhomocysteinemia, vitamin B(12) deficiency, and to a lesser extent, folate deficiency were all related to depressive disorders. For folate deficiency and hyperhomocysteinemia, the association with depressive disorders was substantially reduced after adjustment for functional disability and cardiovascular disease, but for vitamin B(12) this appeared independent. The association of vitamin B(12) and folate with depressive disorders may have different underlying mechanisms. Vitamin B(12) may be causally related to depression, whereas the relation with folate is due to physical comorbidity.
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Hyperhomocysteinemia has been associated with several pregnancy complications. We have investigated the variation of plasma total homocysteine (tHcys) during the 2 last trimesters of normal pregnancy and related it to blood vitamin B12 and folate and to the excretion of the degraded intrinsic factor receptor (IFCR) in urine, in a follow-up study of 15 cases. A significant rise in tHcys was observed between the beginning of the second trimester and the third trimester with respective values (median) 6.1, 5.8 and 6.7 micromol/l (p = 0.038). The tHcys/albumin ratio also increased significantly, while no correlation was found between albumin and folate blood concentration. In contrast, a significant decrease in vitamin B12 was observed (279, 225 and 199 pmol/l, between the 4th and 6th, and the 6th and 9th month, respectively (p = 0.017-0.002)). A significant negative correlation was found between tHcys between the 4th and 9th month of pregnancy and the ratio of vitamin B12 between the 4th and 9th month of pregnancy (r = 0.55, p = 0.037). The urine excretion of IFCR was increased and was not related to vitamin B12 and tHcys. In conclusion, we have observed a rise in tHcys between the beginning of the second trimester and the third trimester of pregnancy which was related to the decreased blood level of vitamin B12. Subclinical deficiency of vitamin B12 should be further investigated in pregnant women who remain on inadequate diet.
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Although maternal folate insufficiency is a risk factor for fetal neural tube defects (NTDs), there is controversy about whether vitamin B12 (B12) insufficiency is also associated with an increased risk of NTDs. To investigate whether low maternal B12 is associated with an increased risk of fetal NTDs. Systematic review. A systematic search of Medline between 1980 and October 2002, with an examination of the citations of all retrieved studies. Studies were included that: (i) used a cohort or case-control design; (ii) included case mothers with a prior or current NTD-affected pregnancy; (iii) assessed a group of unaffected 'controls'; and (iv) measured the vitamin B12 status of all participants. Overall, 17 case-control studies were included, mean sample size 33 cases and 93 controls. In 5/6, mean amniotic fluid B12 concentration was significantly lower in case mothers than in controls. Of 11 that measured maternal serum or plasma B12, three observed a significantly lower mean concentration in case mothers vs. controls, while five others found a non-significant lower trend in the case group. One study observed a significantly higher mean concentration of maternal serum methylmalonic acid among the maternal cases, while another found a non-significant lower mean concentration of plasma holo-transcobalamin. Five studies estimated the risk of NTDs in relation to low B12 or B12-related metabolic markers: it was significantly increased in three studies, with a non-significant trend in the fourth. There seems to be a moderate association between low maternal B12 status and the risk of fetal NTDs. However, several design limitations, and the inclusion of few study participants, may have under-represented this. A large observational study, using reliable and valid indicators of B12 status in early pregnancy, could best assess the association between B12 insufficiency and the risk of fetal NTDs.
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The present prospective study investigated whether elevated total serum homocysteine concentration is a risk factor for cognitive decline. The outcomes were compared to the possible relation between cognition and vitamin B12 or folic acid. Cognitive performance of 144 normal aging individuals (aged 30-80 years) was tested at baseline and after six years of follow-up. Domains of cognitive function addressed were cognitive speed (Letter-Digit Coding test), attention and information processing (Stroop test) and verbal learning and memory (Word Learning Test Total; Delayed Recall). Serum concentrations of homocysteine, folic acid and vitamin B12 were determined. Serum concentrations of homocysteine correlated negatively with cognitive performance on the Word Learning tests at baseline, independent of age, sex, education level or folic acid concentration. Homocysteine concentration at baseline correlated negatively with cognitive performance on the Stroop and Word Learning tests during the whole six-year follow-up period. The folic acid concentration correlated to the Delayed Recall test at baseline only and no correlations were observed for vitamin B12. Thus, while a relation between vitamin B12 or folic acid and cognition was almost absent, elevated homocysteine concentrations were associated with prolonged lower cognitive performance in this normal aging population.
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An association between depression and folate status has been demonstrated in clinical studies, whereas data are sparse on the relationship between depression and other components of 1-carbon metabolism such as vitamin B12, homocysteine, and the methylenetetrahydrofolate reductase 677C-->T polymorphism. The relationship between anxiety and these components is less well known. This study examined the associations between folate, total homocysteine, vitamin B12, and the methylenetetrahydrofolate reductase 677C-->T polymorphism, and anxiety and depression in a large population-based study. Anxiety and depression, measured by the Hospital Anxiety and Depression Scale, were assessed in 5948 subjects aged 46 to 49 years (mean, 47.4 years) and 70 to 74 years (mean, 71.9 years) from the Hordaland Homocysteine Study cohort. By means of logistic regression models, anxiety and depression scores were examined in relation to the factors listed above. Overall, hyperhomocysteinemia (plasma total homocysteine level > or =15.0 micro mol/L [> or =2.02 mg/dL]) (odds ratio, 1.90; 95% confidence interval, 1.11-3.25) and T/T methylenetetrahydrofolate reductase genotype (odds ratio, 1.69; 95% confidence interval, 1.09-2.62), but not low plasma folate or vitamin B12 levels, were significantly related to depression without comorbid anxiety disorder. Plasma folate level was inversely associated with depression only in the subgroup of middle-aged women. None of the investigated parameters showed a significant relationship to anxiety. Our results provide further evidence of a role of impaired 1-carbon metabolism in depression.
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Despite of an increasing body of research the associations between vitamin B12 and folate levels and the treatment outcome in depressive disorders are still unsolved. We therefore conducted this naturalistic prospective follow-up study. Our aim was to determine whether there were any associations between the vitamin B12 and folate level and the six-month treatment outcome in patients with major depressive disorder. Because vitamin B12 and folate deficiency may result in changes in haematological indices, including mean corpuscular volume, red blood cell count and hematocrit, we also examined whether these indices were associated with the treatment outcome. Haematological indices, erythrocyte folate and serum vitamin B12 levels were determined in 115 outpatients with DSM-III-R major depressive disorder at baseline and serum vitamin B12 level again on six-month follow-up. The 17-item Hamilton Depression Rating Scale was also compiled, respectively. In the statistical analysis we used chi-squared test, Pearson's correlation coefficient, the Student's t-test, analysis of variance (ANOVA), and univariate and multivariate linear regression analysis. Higher vitamin B12 levels significantly associated with a better outcome. The association between the folate level and treatment outcome was weak and probably not independent. No relationship was found between haematological indices and the six-month outcome. The vitamin B12 level and the probability of recovery from major depression may be positively associated. Nevertheless, further studies are suggested to confirm this finding.
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One-carbon metabolism is under the influence of folate, vitamin B12 and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR 677 C --> T and 1298 A --> C), of methionine synthase (MTR 2756 C --> G), methionine synthase reductase (MTRR 66 A --> G) and transcobalamin (TCN 776 C --> G). The pathogenesis of neural tube defect (NTD) may be related to this metabolism. The influence of the MTHFR 677 C --> T polymorphism reported in The Netherlands and Ireland can be questioned in southern Italy, France and Great Britain. MTRR, combined with a low level of vitamin B12, increases the risk of NTD and of having a child with NTD in Canada, while TCN 776 GG and MTRR 66 GG mutated genotypes associated with the MTHFR 677 CC wild-type are predictors of NTD cases in Sicily. Down syndrome (DS) is due to a failure of normal chromosomal segregation during meiosis, possibly related to one-carbon metabolism. MTHFR 677 C --> T and MTRR 66 A --> G polymorphisms are associated with a greater risk of having a child with DS in North America, Ireland and The Netherlands. In contrast, MTHFR 677 C --> T has no influence on DS risk in France and Sicily, while homocysteine and MTR 2756 AG/GG genotypes are predictors of DS risk in Sicily. In conclusion, NTD and DS are influenced by the same genetic determinants of one-carbon metabolism. The distinct data produced in different geographical areas may be explained by differences in the nutritional environment and genetic characteristics of the populations.
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to examine the prevalence of vitamin B12 deficiency and folate deficiency in later life in representative samples of the elderly population in the United Kingdom. a population-based cross-sectional analysis of 3,511 people aged 65 years or older from three studies was used to estimate the age-specific prevalence of vitamin B12 deficiency and of folate deficiency. Vitamin B12 deficiency is conventionally diagnosed if serum vitamin B12 < 150 pmol/l ('low vitamin B12'). We defined 'metabolically significant vitamin B12 deficiency' as vitamin B12 < 200 pmol/l and blood total homocysteine >20 micro mol/l. Folate deficiency, which usually refers to serum folate <5 nmol/l, was defined as 'metabolically significant' if serum folate was <7 nmol/l and homocysteine >20 micro mol/l. the prevalence of vitamin B12 deficiency, whether defined as low vitamin B12 or metabolically significant vitamin B12 deficiency increased with age in all three studies, from about 1 in 20 among people aged 65-74 years to 1 in 10 or even greater among people aged 75 years or greater. The prevalence of folate deficiency also increased with age, and was similar to that for vitamin B12 deficiencies, but only about 10% of people with low vitamin B12 levels also had low folate levels. the high prevalence of vitamin B12 and folate deficiency observed in older people indicates a particular need for vigilance for deficiency of these vitamins. Reliable detection and treatment of vitamin deficiency could reduce the risk of deficiency-related disability in old age.
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Vitamin B12 or cobalamin deficiency occurs frequently (> 20%) among elderly people, but it is often unrecognized because the clinical manifestations are subtle; they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. Causes of the deficiency include, most frequently, food-cobalamin malabsorption syndrome (> 60% of all cases), pernicious anemia (15%-20% of all cases), insufficient dietary intake and malabsorption. Food-cobalamin malabsorption, which has only recently been identified as a significant cause of cobalamin deficiency among elderly people, is characterized by the inability to release cobalamin from food or a deficiency of intestinal cobalamin transport proteins or both. We review the epidemiology and causes of cobalamin deficiency in elderly people, with an emphasis on food-cobalamin malabsorption syndrome. We also review diagnostic and management strategies for cobalamin deficiency.
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Homocysteine is an independent risk factor for vascular disease and is associated with dementia in older people. Potential mechanisms include altered endothelial and hemostatic function. We aimed to determine the effects of folic acid plus vitamin B-12, riboflavin, and vitamin B-6 on homocysteine and cognitive function. This was a factorial 2 x 2 x 2, randomized, placebo-controlled, double-blind study with 3 active treatments: folic acid (2.5 mg) plus vitamin B-12 (500 microg), vitamin B-6 (25 mg), and riboflavin (25 mg). We studied 185 patients aged >or=65 y with ischemic vascular disease. Outcome measures included plasma homocysteine, fibrinogen, and von Willebrand factor at 3 mo and cognitive change (determined with the use of the Letter Digit Coding Test and on the basis of the Telephone Interview of Cognitive Status) after 1 y. The mean (+/-SD) baseline plasma homocysteine concentration was 16.5 +/- 6.4 micromol/L. This value was 5.0 (95% CI: 3.8, 6.2) micromol/L lower in patients given folic acid plus vitamin B-12 than in patients not given folic acid plus vitamin B-12 but did not change significantly with vitamin B-6 or riboflavin treatment. Homocysteine lowering with folic acid plus vitamin B-12 had no significant effect, relative to the 2 other treatments, on fibrinogen, von Willebrand factor, or cognitive performance as measured by the Letter Digit Coding Test (mean change: -1; 95% CI: -2.3, 1.4) and the Telephone Interview of Cognitive Status (-0.7; 95% CI: -1.7, 0.4). Oral folic acid plus vitamin B-12 decreased homocysteine concentrations in elderly patients with vascular disease but was not associated with statistically significant beneficial effects on cognitive function over the short or medium term.
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Homocysteine is a risk factor for cardiovascular disease. We evaluated the efficacy of homocysteine-lowering treatment with B vitamins for secondary prevention in patients who had had an acute myocardial infarction. The trial included 3749 men and women who had had an acute myocardial infarction within seven days before randomization. Patients were randomly assigned, in a two-by-two factorial design, to receive one of the following four daily treatments: 0.8 mg of folic acid, 0.4 mg of vitamin B12, and 40 mg of vitamin B6; 0.8 mg of folic acid and 0.4 mg of vitamin B12; 40 mg of vitamin B6; or placebo. The primary end point during a median follow-up of 40 months was a composite of recurrent myocardial infarction, stroke, and sudden death attributed to coronary artery disease. The mean total homocysteine level was lowered by 27 percent among patients given folic acid plus vitamin B12, but such treatment had no significant effect on the primary end point (risk ratio, 1.08; 95 percent confidence interval, 0.93 to 1.25; P=0.31). Also, treatment with vitamin B6 was not associated with any significant benefit with regard to the primary end point (relative risk of the primary end point, 1.14; 95 percent confidence interval, 0.98 to 1.32; P=0.09). In the group given folic acid, vitamin B12, and vitamin B6, there was a trend toward an increased risk (relative risk, 1.22; 95 percent confidence interval, 1.00 to 1.50; P=0.05). Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infarction. A harmful effect from combined B vitamin treatment was suggested. Such treatment should therefore not be recommended. (ClinicalTrials.gov number, NCT00266487.).
Article
BACKGROUND: Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive. OBJECTIVE: The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged >/=70 y with mild vitamin B-12 deficiency. DESIGN: In a double-blind, placebo-controlled trial, 195 subjects were randomly assigned to receive 1000 microg vitamin B-12, 1000 microg vitamin B-12 + 400 microg folic acid, or placebo for 24 wk. Vitamin B-12 status was assessed on the basis of methylmalonic acid, total homocysteine (tHcy), and holotranscobalamin (holoTC) concentrations before and after 12 and 24 wk of treatment. Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention, construction, sensomotor speed, memory, and executive function. RESULTS: Vitamin B-12 status did not change significantly after treatment in the placebo group; however, oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency. Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36%. Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone (P = 0.0036). Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains. CONCLUSION: Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function.
Article
Background: Homocysteine is an independent risk factor for vascular disease and is associated with dementia in older people. Potential mechanisms include altered endothelial and hemostatic function. Objective: We aimed to determine the effects of folic acid plus vitamin B-12, riboflavin, and vitamin B-6 on homocysteine and cognitive function. Design: This was a factorial 2 × 2 × 2, randomized, placebo-controlled, double-blind study with 3 active treatments: folic acid (2.5 mg) plus vitamin B-12 (500 μg), vitamin B-6 (25 mg), and riboflavin (25 mg). We studied 185 patients aged ≥65 y with ischemic vascular disease. Outcome measures included plasma homocysteine, fibrinogen, and von Willebrand factor at 3 mo and cognitive change (determined with the use of the Letter Digit Coding Test and on the basis of the Telephone Interview of Cognitive Status) after 1 y. Results: The mean (±SD) baseline plasma homocysteine concentration was 16.5 ± 6.4 μmol/L. This value was 5.0 (95% CI: 3.8,6.2) μmol/L lower in patients given folic acid plus vitamin B-12 than in patients not given folic acid plus vitamin B-12 but did not change significantly with vitamin B-6 or riboflavin treatment. Homocysteine lowering with folic acid plus vitamin B-12 had no significant effect, relative to the 2 other treatments, on fibrinogen, von Willebrand factor, or cognitive performance as measured by the Letter Digit Coding Test (mean change: -1; 95% CI: -2.3, 1.4) and the Telephone Interview of Cognitive Status (-0.7; 95% CI: -1.7,0.4). Conclusion: Oral folic acid plus vitamin B-12 decreased homocysteine concentrations in elderly patients with vascular disease but was not associated with statistically significant beneficial effects on cognitive function over the short or medium term.
Article
Impairment of folate and cobalamin (vitamin B12) metabolism has been observed in families with neural tube defects (NTDs). Genetic variants of enzymes in the homocysteine remethylation pathway might act as predisposing factors contributing to NTD risk. The first polymorphism linked to increased NTD risk was the 677C→T mutation in methylenetetrahydrofolate reductase (MTHFR). We now report a polymorphism in methionine synthase reductase (MTRR), the enzyme that activates cobalamin-dependent methionine synthase. This polymorphorism, 66A→G (I22M), has an allele frequency of 0.51 and increases NTD risk when cobalamin status is low or when the MTHFR mutant genotype is present. Genotypes and cobalamin status were assessed in 56 patients with spina bifida, 58 mothers of patients, 97 control children, and 89 mothers of controls. Cases and case mothers were almost twice as likely to possess the homozygous mutant genotype when compared to controls, but this difference was not statistically significant. However, when combined with low levels of cobalamin, the risk for mothers increased nearly five times (odds ratio (OR) = 4.8, 95% CI 1.5–15.8); the OR for children with this combination was 2.5 (95% CI 0.63–9.7). In the presence of combined MTHFR and MTRR homozygous mutant genotypes, children and mothers had a fourfold and threefold increase in risk, respectively (OR = 4.1, 95% CI 1.0–16.4; and OR = 2.9, 95% CI 0.58–14.8). This study provides the first genetic link between vitamin B12 deficiency and NTDs and supports the multifactorial origins of these common birth defects. Investigation of this polymorphism in other disorders associated with altered homocysteine metabolism, such as vascular disease, is clearly warranted.
Article
Background and purpose: Epidemiological and laboratory studies suggest that increasing concentrations of plasma homocysteine (total homocysteine [tHcy]) accelerate cardiovascular disease by promoting vascular inflammation, endothelial dysfunction, and hypercoagulability. Methods: We conducted a randomized controlled trial in 285 patients with recent transient ischemic attack or stroke to examine the effect of lowering tHcy with folic acid 2 mg, vitamin B12 0.5 mg, and vitamin B6 25 mg compared with placebo on laboratory markers of vascular inflammation, endothelial dysfunction, and hypercoagulability. Results: At 6 months after randomization, there was no significant difference in blood concentrations of markers of vascular inflammation (high-sensitivity C-reactive protein [P=0.32]; soluble CD40L [P=0.33]; IL-6 [P=0.77]), endothelial dysfunction (vascular cell adhesion molecule-1 [P=0.27]; intercellular adhesion molecule-1 [P=0.08]; von Willebrand factor [P=0.92]), and hypercoagulability (P-selectin [P=0.33]; prothrombin fragment 1 and 2 [P=0.81]; D-dimer [P=0.88]) among patients assigned vitamin therapy compared with placebo despite a 3.7-micromol/L (95% CI, 2.7 to 4.7) reduction in total homocysteine (tHcy). Conclusions: Lowering tHcy by 3.7 micromol/L with folic acid-based multivitamin therapy does not significantly reduce blood concentrations of the biomarkers of inflammation, endothelial dysfunction, or hypercoagulability measured in our study. The possible explanations for our findings are: (1) these biomarkers are not sensitive to the effects of lowering tHcy (eg, multiple risk factor interventions may be required); (2) elevated tHcy causes cardiovascular disease by mechanisms other than the biomarkers measured; or (3) elevated tHcy is a noncausal marker of increased vascular risk.
Article
We examined the relationship between a functional polymorphism (667C-->T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-->carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.
Article
The relationship between vitamin status and cognitive functioning has been addressed in several recent studies with inconclusive results. The purpose of this study was to examine separate and combined effects of serum vitamin B12 and folic acid on episodic memory functioning in very old age. Four study groups were selected from a population-based sample of healthy very old adults (90-101 years of age): normal B12/normal folic acid, low B12/normal folic acid, normal B12/low folic acid, and low B12/low folic acid. Cutoff levels were set at 180 pmol/L for vitamin B12 and at 13 nmol/L for folic acid. Subjects completed two episodic recall tasks (objects and words) and two episodic recognition tasks (faces and words). Neither vitamin affected recognition or primary memory. Most interesting, although B12 was unrelated to recall performance, subjects with low folic acid levels showed impairment in both word recall and object recall. These results replicate and extend previous findings that folic acid may be more critical than B12 to memory functioning in late life. The selective effects of folic acid on episodic recall were discussed in terms of encoding and retrieval mechanisms, as well as in relation to brain protein synthesis.
Article
Individuals with different forms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, carriers of the C677T mutation versus wild type, show differences in enzyme levels; these differences have been hypothesized to be related to DNA methylation and, perhaps, to the nucleotide pool size. Using data from an incident case-control study, we evaluated the combined effect of dietary intake of folate, methionine, vitamin B6, vitamin B12, and alcohol and various forms of the MTHFR gene on risk of colon cancer. Individuals homozygous for the variant form of the MTHFR gene (TT) had a slightly lower risk of colon cancer than did individuals who were wild type [CC, odds ratio (OR) = 0.8, 95% confidence interval (CI) = 0.6-1.1 for men; and OR = 0.9, 95% CI = 0.6-1.2 for women]. High levels of intake of folate, vitamin B6, and vitamin B12 were associated with a 30-40% reduction in risk of colon cancer among those with the TT relative to those with low levels of intake who were CC genotype. Associations were stronger for proximal tumors, in which high levels of intake of these nutrients were associated with a halving of risk among those with the TT genotype. The inverse association with high levels of these nutrients in those with the TT genotype was stronger among those diagnosed at an older age. Although imprecise, the inverse association with the low-risk diet that was high in folate and methionine and without alcohol was observed for both the TT genotype (OR = 0.4 95% CI = 0.1-0.9) and the CC/CT genotype (OR = 0.6, 95% CI = 0.4-1.0), but this association was not seen with the high-risk diet for either the TT or CC/CT genotype. Although associations were generally weak, these findings suggest that those with differing MTHFR genotypes may have different susceptibilities to colon cancer, based on dietary consumption of folate, vitamin B6, and vitamin B12.
Article
We previously reported (J. Chen et al., Cancer Res., 56: 4862-4864, 1996; J. Ma et al., Cancer Res., 57: 1098-1102, 1997) that a 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism (677C-->T, ala-->val) was associated with lower risk of colorectal cancer. In this study, we examined the relationship of a polymorphism (2756A-->G, asp-->gly) in the gene (MTR) for methionine synthase, another important enzyme in the same folate/methionine/homocyst(e)ine metabolic pathway, with risk of colorectal cancer among 356 cases and 476 cancer-free controls. The frequency of the homozygous variant genotype (gly/gly) was slightly lower among cases (3%) than controls (5%). The odds ratio for the gly/gly genotype was 0.59 [95% confidence interval (CI), 0.27-1.27] compared with those with the homozygous wild type (asp/asp). There were no significant differences in plasma levels of folate, vitamin B12, and homocyst(e)ine (tHcy) among the MTR genotypes, in contrast to the MTHFR polymorphism. However, similar to the interaction observed for the MTHFR polymorphism among men who consumed less than 1 alcoholic drink/day, those with the gly/gly genotype had a lower risk of colorectal cancer with an odds ratio of 0.27 (95% CI, 0.09-0.81) compared with those with the asp/asp genotype. The possible association of the MTR polymorphism with lower risk of colorectal cancer especially among those with low alcohol consumption, in the same direction as for the MTHFR polymorphism, is intriguing. However, our study had limited statistical power because of the low frequency of the MTR variant genotype, which is reflected in the wide CIs. Hence, these findings need to be confirmed in larger populations.
Article
The effect of homocysteine-lowering treatment on thrombin generation was investigated in 17 subjects with hyperhomocysteinemia (aged 22-60 years), 11 of whom had symptomatic atherosclerotic vascular disease. All subjects had fasting total homocysteine levels above 16 micromol/L. The formation of thrombin was assessed by measuring thrombin-antithrombin III complexes and prothrombin fragment 1+2 in peripheral venous blood and in the bleeding time blood collected at 30-second intervals from skin incisions on a forearm. All the tests were performed before and after an 8-week treatment with folic acid p.o. 5 mg/day, vitamin B6 p.o. 300 mg/day, and vitamin B12 i.m. 1000 microg given on a weekly basis. Following the 8-week therapy, the median plasma homocysteine concentration became significantly reduced from 20 to 10 micromol/L, while plasma levels of fibrinogen, prothrombin, and antithrombin III as well as activity of protein C, S, and factor VII showed no changes. Vitamin treatment was associated with a significant fall in thrombin-antithrombin III complexes and prothrombin fragment 1+2 concentrations in peripheral venous blood. Bleeding time became prolonged by about 60 seconds. At sites of hemostatic plug formation, plasma concentrations of both thrombin markers significantly decreased. Compared with pretreatment values, significantly less thrombin was produced during the first 3 minutes of bleeding after homocysteine-lowering therapy. In subjects with hyperhomocysteinemia a reduction of plasma fasting homocysteine concentration by folic acid and vitamins B12 and B6 administration is associated with attenuation of thrombin generation both in peripheral blood and at sites of hemostatic plug formation.
Article
Vitamin B12 assay is part of the routine investigation of dementia, although few studies have investigated the effects of treatment on cognition. We examined the effects of B12 treatment on neuropsychological function and disease progression in patients presenting with dementia or cognitive impairment. From 1432 patients who were assessed at the Bristol Memory Disorders Clinic, 125 patients with low serum B12 were identified. Sixty-six patients presenting with dementia, and 22 with cognitive impairment were seen for a second assessment after treatment. Changes in neuropsychological test scores were compared with those of patients with normal serum B12, matched by age and diagnosis. The majority of patients with low serum B12 had normal Hb and MCV values. We found no cases of reversible B12 deficiency dementia. The B12 treatment patients who presented with dementia showed no significant improvement, and no less deterioration, in their neuropsychological function than their matched group. However, a treatment effect was demonstrated among the patients presenting with cognitive impairment. These improved significantly compared to matched patients on the verbal fluency test (p<0.01). All patients with cognitive impairment should be investigated for B12 deficiency. Vitamin B12 treatment may improve frontal lobe and language function in patients with cognitive impairment, but rarely reverses dementia.
Article
The objective of this study was to examine whether patients with Alzheimer's disease (AD) with subnormal vitamin B12 levels show more frequent behavioural and psychological symptoms of dementia (BPSD) than AD patients with normal vitamin B12 levels. The design was a prospective case-control study. The study took place at a memory-clinic of a department of geriatric medicine in a teaching hospital. There were seventy-three consecutive outpatients with probable AD, including 61 patients with normal and 12 patients with subnormal (<200 pg/ml) vitamin B12. BPSD were measured using the subscales disturbed behaviour and mood of the Nurses' Observation Scale for Geriatric Patients (NOSGER), the Cornell Scale for Depression and the four criteria for personality change in dementia from the International Classification of Diseases (ICD-10). Controlling for dementia duration and degree of severity of the cognitive deficits, there were significant inverse associations between vitamin B12 status and ICD-10 irritability (p=0.045) and NOSGER subscale disturbed behaviour (p=0.015). Low vitamin B12 serum levels are associated with BPSD in AD. Vitamin B12 could play a role in the pathogenesis of behavioural changes in AD.
Article
Due to its role in the synthesis and repair of DNA, folate may protect against the development of cervical cancer. Prospective data on the possible association between folate and cervical cancer have been lacking. There is also a paucity of prospective evidence concerning the possible associations between cervical cancer and vitamin B12, which shares pathways with folate, and homocysteine, a marker of low B vitamin concentrations. A nested case-control study was conducted to prospectively evaluate the associations between cervical cancer and serum concentrations of folate, vitamin B12, and homocysteine. Among a community-based cohort of women who donated blood in 1974 for a serum bank in Washington County, Maryland, 39 cases of cervical cancer diagnosed between 1975 and mid-1990 were included in the study (13 cases of invasive cervical cancer and 26 cases of carcinoma in situ). Two controls were matched to each case by age, race, and sex. Stored serum from the cases and controls was assayed for folate, B12, and homocysteine concentrations. For folate, adjusted odds ratios were 1.0, 0.62, and 0.60 for the low to high thirds of the serum concentrations, respectively, a trend in the protective direction that was not statistically significant (P for trend = 0.42). Overall, the results for vitamin B12 tended to mimic those for folate, whereas the associations for homocysteine tended to be in the opposite direction. None of the results of this study were statistically significant, but patterns of the associations are in accord with hypothesized mechanistic pathways concerning B vitamins and cervical cancer.
Article
We investigated the relation between cobalamin deficiency, clinical changes and brain function in dementia patients. On admittance to the clinic, 24 patients had cobalamin deficiency, and dementia with additional symptoms of delirium. During cobalamin supplementation, the patients underwent repeated regional cerebral blood flow (rCBF) studies, psychiatric evaluations, and in some cases assessment with MMSE and the Organic Brain Syndrome scale. Fifteen patients who showed mild to moderate dementia improved clinically, and also showed a concomitant increase in their general CBF after treatment. In contrast, 9 patients who were severely demented showed no obvious clinical improvement, and no general blood flow change, although some regional flow increases were seen in sensory motor areas. We conclude that symptoms which probably indicated superimposed delirium such as clouding of consciousness, disorientation and clinical fluctuation, responded to the vitamin B12 supplementation, while the underlying dementia condition remained basically unchanged. The clinical improvement was also mirrored in general and focal rCBF changes.
Article
This study assessed the association of dietary folate, vitamin B6, and vitamin B12 with cardiovascular mortality. Poisson regression analyses assessed coronary/cerebrovascular mortality rates via nutrient data obtained from the National Nutrition Survey, which recorded 7-day food intakes from a national sample of 21,155 households. In regard to coronary mortality, male and female rate ratios (highest vs lowest quintile) were 0.83 (95% confidence interval [CI] = 0.77, 0.91) and 0.95 (95% CI = 0.86, 1.05), respectively, for folate and 0.74 (95% CI = 0.65, 0.84) and 0.86 (95% CI = 0.73, 0.99), respectively, for B12. Intake of folate and B6 (but not B12) was significantly associated with cerebrovascular mortality. B vitamins are associated with cardiovascular mortality in the general population.
Article
Periconceptional folic acid supplementation reduces the risk of neural tube defects (NTD). Homocysteine levels are elevated in mothers of NTD children, which may be due to decreased cellular vitamin B12 levels, as vitamin B12 is a cofactor for the methylation of homocysteine. Transcobalamin II (TC II) transports vitamin B12 to the tissues. To examine whether altered plasma transcobalamin levels are a risk factor for NTD, we determined the apo and holo form of TC II and haptocorrin (TCI+TCIII), vitamin B12 and homocysteine concentrations in the plasma of 46 mothers with NTD children, and in 73 female controls. Holo-tc II levels and holo-tc II percentages (holo-tc II/total tc II) in the first quartile of the control distribution were related to a three-fold (OR 2.9, 95%CI 0.9-9.2) and five-fold (OR 5.0, 95%CI 1.3-19.3) risk, respectively, for having a child with NTD, when compared with the last quartile. Homocysteine levels were significantly higher among individuals with low holo-tc II, low total vitamin B12 concentrations and low holo-tc II percentages. These low holo-tc II percentages are probably caused by reduced affinity of TC II for vitamin B12, which may be explained by genetic variation in the TC II gene. Vitamin B12 supplementation might therefore be warranted, in addition to folate, in the prevention of NTD.
Article
A deficiency of any of the micronutrients: folic acid, Vitamin B12, Vitamin B6, niacin, Vitamin C, Vitamin E, iron, or zinc, mimics radiation in damaging DNA by causing single- and double-strand breaks, oxidative lesions, or both. For example, the percentage of the US population that has a low intake (<50% of the RDA) for each of these eight micronutrients ranges from 2 to >20%. A level of folate deficiency causing chromosome breaks was present in approximately 10% of the US population, and in a much higher percentage of the poor. Folate deficiency causes extensive incorporation of uracil into human DNA (4 million/cell), leading to chromosomal breaks. This mechanism is the likely cause of the increased colon cancer risk associated with low folate intake. Some evidence, and mechanistic considerations, suggest that Vitamin B12 (14% US elderly) and B6 (10% of US) deficiencies also cause high uracil and chromosome breaks. Micronutrient deficiency may explain, in good part, why the quarter of the population that eats the fewest fruits and vegetables (five portions a day is advised) has about double the cancer rate for most types of cancer when compared to the quarter with the highest intake. For example, 80% of American children and adolescents and 68% of adults do not eat five portions a day. Common micronutrient deficiencies are likely to damage DNA by the same mechanism as radiation and many chemicals, appear to be orders of magnitude more important, and should be compared for perspective. Remedying micronutrient deficiencies should lead to a major improvement in health and an increase in longevity at low cost.
Article
Hyperhomocyst(e)inemia is emerging as a possible risk factor for stroke, possibly because of accelerated atherosclerosis. There are no previous publications evaluating homocyst(e)ine in young Asian ischemic stroke patients. We conducted a case-control study examining homocyst(e)ine, vitamin B12, and folate levels in young, first-ever Asian ischemic stroke patients. We prospectively recruited 109 consecutive young (<50 years) first-ever hospitalized ischemic stroke patients and 88 age/gender-matched hospital-based controls during a period of 18 months. Prevalence of vascular risk factors was assessed; fasting homocyst(e)ine, vitamin B12, and folate were assayed. Stroke mechanisms were subtyped using TOAST study criteria. Mean age was 43.8 (cases) and 43.1 (controls) years; 71.6% were male (cases and controls). Diabetes mellitus, hypertension, and hyperlipidemia were significantly more prevalent in cases. Mean fasting homocyst(e)ine levels were significantly higher in cases (13.7 micro mol/L, 95% CI: 12.7 to 14.9) than controls (10.8 micro mol/L, 95% CI: 9.9 to 11.8, P<0.001). Mean vitamin B12 levels were significantly lower in cases (299.5 pmol/L, 95% CI: 266.7 to 332.3) than controls (394.5 pmol/L, 95% CI: 357.9 to 431.0, P<0.001). Folate levels were not significantly different. Mean homocyst(e)ine levels were significantly elevated in large-artery strokes (16.9 micro mol/L, 95% CI: 14.5 to 19.7, P<0.001) but not other stroke subtypes compared with controls. Compared with the lowest homocyst(e)ine quartile, the highest quartile was significantly associated with an adjusted odds ratio of 4.3 for ischemic stroke and 25.3 for large-artery stroke. Using a logistic regression model, the adjusted odds ratio was 5.17 (95% CI: 1.96 to 13.63, P=0.001) for every 1 micro mol/L increase in log homocyst(e)ine. Hyperhomocyst(e)inemia is an independent risk factor for ischemic strokes in young Asian adults. The relationship between increasing homocyst(e)ine and stroke risk is strong, graded, and significant. The association with large-artery strokes suggests that hyperhomocyst(e)inemia may increase stroke risk via a proatherogenic effect.
Article
Many regimens using different doses of folic acid (FA) alone or with supplementation of B-complex vitamins (BCV) have been tested for the reduction of total homocysteine (tHcy) levels in hemodialysis (HD) patients. BCV are usually administered orally and for a short period. In the present study, we assessed the effect of long-term intravenous (IV) BCV on serum tHCy levels in HD patients, and the effect produced by moderate oral supplementation with FA. In a cohort of 37 patients under chronic HD treatment for a mean of 50.2 +/- 46.7 months, serum concentrations of tHcy, folate and vitamin B12 were determined at the end of four sequential periods: (A) three months without any FA supplementation, (B) three months with oral supplementation of 5 mg of FA three times weekly, (C) six months without FA supplementation, and (D) three months without BVC or FA supplementation. From the start of HD treatment and throughout the study until the beginning of period D, patients received a standard IV dose of BCV (B1 250 mg + B6 250 mg + B12 1.5 mg) three times per week, post-dialysis. At the end of period B, mean serum tHcy levels were significantly lower than in periods A and C (13.7 +/- 3.6 micromol/L vs 19.6 +/- 10.8 micromol/L and 21.3 +/- 9.4 micromol/L, respectively, p < 0.001) and mean serum folate levels were significantly higher (20.7 +/- 7.4 ng/mL vs 5.0 +/- 2.8 ng/mL and 4.5 +/- 1.4 ng/mL, respectively, p < 0.01). At the end of period D, mean serum tHcy levels were significantly higher than in all the previons periods (29.3 +/- 13.5 micromol/L, p < 0.001). Twenty-six of the 37 patients (70.2%) had normal (< 15 micromol/L) serum tHcy levels at the end of period B and only one (2.7%) had normal tHcy at the end of period D. Mean serum vitamin B12 levels at the end of periods A, B and C were 100 times the usual normal values. At the end of period D, although significantly lowered (p < 0.001), they remained above the normal range. Long-term high-dose BCV IV three times a week post-dialysis reduced serum tHcy levels only when combined with oral FA supplementation.
Article
Many women do not receive folic acid supplements before conception. In response, most of Canada's cereal grain products were being fortified with folic acid by January, 1998, thereby providing an additional 0.1-0.2 mg per day of dietary folate to the Canadian population. We assessed the effect of supplementation on prevalence of open neural tube defects in the province of Ontario. Among 336 963 women who underwent maternal serum screening over 77 months, the prevalence of open neural tube defects declined from 1.13 per 1000 pregnancies before fortification to 0.58 per 1000 pregnancies thereafter (prevalence ratio 0.52, 95% CI 0.40-0.67, p<0.0001). At a population level, folic acid food fortification is associated with a pronounced reduction in open neural tube defects.
Article
The pathogenic mechanism of neural tube defects may involve genetic polymorphisms and nutritional factors related to homocysteine metabolism. We evaluated the association of polymorphisms of three genes affecting vitamin B12-dependent remethylation of homocysteine, transcobalamin (TC), methionine synthase (MTR) and MTR reductase (MTRR), combined or not with methylenetetrahydrofolate reductase (MTHFR), with the risk of having neural tube defect in 40 children with spina bifida and 58 matched controls from South Italy. MTR 2756 AG/GG, TC 777 CG/GG /MTHFR 677 CC and MTRR 66 GG /MTHFR 677 CC genotypes increased the risk with odds ratios of 2.6 (P=0.046), 2.4 (P=0.028) and 4.5 (P=0.023), respectively. In contrast, MTHFR 677 TT was protective (odds ratio=0.11, P=0.009). In conclusion, genetic determinants affecting the cellular availability or MTRR-dependent reduction of B12 may increase the risk of spina bifida.