Retinal changes associated with multivitamin deficiency before and after supplementation.

BACKGROUND: Nutritional visual defects are apparently uncommon nowadays in developed nations. Retinal change-related visual defects caused by hypovitaminoses may be underdiagnosed. AIM OF THE STUDY: To investigate the retinal structural and functional changes in a patient with multivitamin deficiency before and during vitamin supplementation. METHODS: A 51-year-old female had been on vegetarian diet as a child, and on restrict vegan diet during the last 2 years, developing severe bilateral deterioration of visual function and polyneuropathy. Blood test revealed low levels of vitamin A, B6 and D. The patient underwent examinations with optical coherence tomography (OCT), computerized visual field examination (VF), electroretinography (ERG), visual evoked potentials (VEP) and neurography before and after vitamin supplementation. RESULTS: Visual acuity (VA) was 20/1000 and VF examination showed central scotoma in both eyes. Color vision was significantly affected. Full-field ERG showed normal rod and cone function, but a clearly reduced central peak was registered in multifocal ERG (mf-ERG), indicating impaired fovea function. VEP showed delayed latency and low amplitude of P100 in both eyes. Neurography showed sensory polyneuropathy. OCT showed significant thinning of macular ganglion cell plus inner plexiform layer (GCIPL) with rapid progression. Retinal nerve fiber layer (RNFL) was preserved and normal, which is in contrast to neuroinflammatory conditions. After 2.5 years of multivitamin supplementation, the visual functions were improved. GCIPL thickness was stable without further deterioration. CONCLUSIONS: Multivitamin deficiency results in progressive thinning of GCIPL with severe visual deterioration. In contrast to neuroinflammation, RNFL is preserved and normal. Stabilized GCIPL during vitamin supplementation was associated with improved visual function. OCT provides a sensitive and objective measure for differential diagnosis, monitoring retinal change and response to therapy.

Update on Biotin Therapy in Dermatology: Time for a Change.

Biotin (vitamin B7 or H) is found in milk, nuts, egg yolks, cereals, supplements, synthesized by intestinal bacteria, and is required for gluconeogenesis, fatty acid synthesis and amino acid catabolism.

Metabolic Consequences of Supplemented Methionine in a Clinical Context.

The central position of methionine (Met) in protein metabolism indicates the importance of this essential amino acid for growth and maintenance of lean body mass. Therefore, Met might be a tempting candidate for supplementation. However, because Met is also the precursor of homocysteine (Hcy), a deficient intake of B vitamins or excessive intake of Met may result in hyperhomocysteinemia (HHcy), which is a risk factor for cardiovascular disease. This review discusses the evidence generated in preclinical and clinical studies on the importance and potentially harmful effects of Met supplementation and elaborates on potential clinical applications of supplemental Met with reference to clinical studies performed over the past 20 y. Recently acquired knowledge about the NOAEL (no observed adverse effect level) of 46.3 mg · kg-1 · d-1 and the LOAEL (lowest observed adverse effect level) of 91 mg · kg-1 · d-1 of supplemented Met will guide the design of future studies to further establish the role of Met as a potential (safe) candidate for nutritional supplementation in clinical applications.

Multiple vitamin deficiencies additively increase the risk of incident fractures in Japanese postmenopausal women.

The associations of multiple vitamin deficiencies on incident fractures were uncertain, the relationships between serum vitamin markers and incident bone fractures were investigated in Japanese postmenopausal women. The number of deficiencies was additively associated with incident fracture after adjustment for possible confounding factors including the treatment of osteoporosis. INTRODUCTION: To evaluate the associations of multiple vitamin deficiencies on incident fractures, the relationships between serum vitamin markers and incident bone fractures were investigated in Japanese postmenopausal women. METHODS: This analysis used a subset of the ongoing cohort maintained by a primary care institution. Inclusion criteria of the present study were postmenopausal women aged ≥ 50 years, without vitamin supplementation and secondary osteoporosis. Baseline serum concentrations of 25-hydroxyvitamin D (25(OH)D), undercarboxylated osteocalcin (ucOC), and homocysteine (Hcy) were measured to assess vitamin D, vitamin K, and vitamin B, respectively. Since 25(OH) D positively relates to vitamin D, ucOC and Hcy negatively relate to vitamin K and vitamin B nutrients, respectively, the subjects with lower (25(OH)D) or higher (ucOC or Hcy) values than each median value was defined as subjects with the corresponding vitamin deficiency. Subjects were divided into four groups according to the number of deficiency: no deficiency, single deficiency, double deficiencies, and triple deficiencies. Relationships between the vitamin deficiencies and incident fractures were evaluated by Cox regression analysis. RESULTS: A total of 889 subjects were included in this analysis; their mean and SD age was 68.3 ± 9.5 years, and the follow-up period was 6.3 ± 5.1 years. The numbers of subjects in the four groups were 139 (15.6%), 304 (34.2%), 316 (35.5%), and 130 (14.6%) for the groups with no, single, double, and triple deficiencies, respectively. Incident fractures were observed in 264 subjects (29.7%) during the observation period. The number of deficiencies was significantly associated with incident fracture (hazard ratio 1.25, 95% confidence interval 1.04-1.50, P = 0.018) after adjustment for possible confounding factors including the treatment of osteoporosis. CONCLUSION: Accumulation of vitamin deficiencies was related to incident fractures.

Obesity, related diseases and their relationship with vitamin D deficiency in adolescents.

INTRODUCTION: The rise in prevalence of obesity has occurred concomitantly to that of vitamin D deficiency (VDD). The aim of this narrative review was to describe the relationship between obesity and such related diseases as VDD in adolescents, in an effort to warn of the risks of this deficiency during this period of growth and development. METHODS: We searched the electronic databases PubMed, Medline, Scielo, Science Direct and Lilacs for articles from between 2000 and 2015 on the topics obesity and obesity-related diseases and VDD in adolescents. We included articles written in English, Spanish and Portuguese of the analytical variety (transverse and longitudinal), systematic reviews, meta-analysis and controlled clinical trials on humans, and excluded studies that were done on animals, inconclusive or with undefined methodology. RESULTS: We produced an overview of VDD in obesity, in cardiovascular diseases, in diabetes mellitus, in systemic hypertension, and in dyslipidemia. The prevalence of VDD was considered high in obese adolescents and their relationship with the obesity and related diseases was found in adolescents. These findings forewarn of possible clinical repercussions in the health of the adolescents, foremost because of how essential vitamin D is to growth and development, and for its interaction with obesity and obesity-related diseases. CONCLUSION: The worldwide rise in the obesity rate alongside the progressively increasing of vitamin D deficiency in adolescents is alarming. This relationship of VDD with the obesity and related diseases was found in adolescents. Vitamin D supplementation is considered promising measure to take with obese adolescents.

Multiple sclerosis-like diagnosis as a complication of previously treated malaria in an iron and vitamin D deficient Nigerian patient.

In contrast to malaria, multiple sclerosis (MS) is infrequently found in Black Africans. We describe a 29 year old Nigerian female who developed an MS-like condition with symptoms similar to relapsing-remitting MS following malaria infection, leading to a diagnosis of MS. However, absence of hyperintense lesions in the brain and spinal cord presented a conundrum since not all the diagnostic criteria for MS were met. Pathology supported genetic testing (PSGT) was applied to combine family and personal medical history, lifestyle factors, and biochemical test results for interpretation of genetic findings. This approach provides a means of identifying risk factors for different subtypes of demyelinating disease. The patient was subsequently treated according to an individualised intervention program including nutritional supplementation as well as a change in diet and lifestyle. Deficiencies of vitamin B12, iron and vitamin D were addressed. Genetic analysis revealed absence of the HLA DRB1*1501 allele, considered to be the most prominent genetic risk factor for MS. Extended mutation analysis identified variations in three genes in the folate-vitamin B12 metabolic pathway, which could have increased the patient's sensitivity to the antifolate drugs used to treat the malaria. A glutathione-S-transferase GSTM1 null allele, previously associated with neurological complications of malaria, was also detected. Furthermore, a heterozygous variation in the iron-related transmembrane protease serine 6 (TMPRSS6) gene, rs855791 was found, which could have impacted the patient's iron status following two successive blood donations and exposure to malaria preceding the MS diagnosis. PSGT identifies relevant risk factors for demyelinating disorders resembling MS and uses the data for individualised treatment programs, and to systematically build a database that can provide evidence in large patient cohorts. Follow-up investigations may be suggested, such as whole exome sequencing in selected cases, to ensure that remyelination and restoration of function are achieved.

Vitamin D Levels in Infants With Biliary Atresia: Pre- and Post-Kasai Portoenterostomy.

OBJECTIVES: Infants with biliary atresia (BA) are at high risk of vitamin D deficiency. We aimed to determine the prevalence and factors influencing vitamin D levels at presentation and post-Kasai portoenterostomy (KPE). METHODS: Single-centre retrospective review of infants with BA who underwent KPE. Pre- and postoperatively 25-hydroxyvitamin D (25-OHVD), liver and bone biochemistry data were collected. 25-OHVD levels <10 and 10 to 20 ng/mL were defined as vitamin D "deficiency" and "insufficiency," respectively. RESULTS: One hundred twenty-nine infants with BA (isolated n = 101, developmental n = 28, and white n = 79; non-white n = 50) were included in this study. At presentation, 75 of 92 (81%) were vitamin D deficient and only 1 infant had a level >20 ng/mL. Median 25-OHVD levels were 5(2-23), 17(2-72), 15(2-80), 17(2-69), and 23(2-98) ng/mL at pre-KPE, 1, 4, 6, and 12 months postoperation. There was no difference in 25-OHVD levels between the isolated and developmental groups with BA. Pre-KPE, white infants had significantly higher levels than non-white infants (6[2-23] vs 3[2-14] ng/mL, P = 0.01). Post-KPE 25-OHVD levels correlated well with liver and bone biochemical variables (eg, at 6 months: bilirubin rs = -0.34; P < 0.001, alkaline phosphatase rs = -0.46; P < 0.00001, and phosphate rs = 0.49; P < 0.00001). CONCLUSIONS: 25-OHVD deficiency is invariable at presentation in infants with BA, irrespective of its likely aetiology, and is more severe in non-white infants. Despite routine parenteral and enteral supplementation, low 25-OHVD levels persist post KPE especially in icteric infants. More aggressive vitamin D supplementation and monitoring in this population is paramount.

Clinical, etiological and therapeutic aspects of cerebral folate deficiency.

Cerebral folate deficiency is defined as any neurological condition associated with low cerebrospinal fluid folate concentrations. It is becoming increasingly associated with several neurological diseases, either genetic or environmental. Treatment of cerebral folate deficiency by folate supplementation is generally effective, improving the neurological outcome of some patients. However, to treat cerebral folate deficiency, the proper choice of one of the available folate forms is essential. The distinct brain folate metabolism features compared with peripheral folate metabolic pathways strongly suggest the investigation of different folate forms, such as the biologically active folinic acid and 5-methyltetrahydrofolate, since they are efficiently transported to the brain. Regarding the oral doses of the different folate forms, despite the fact that there are some recommendations, there is no general consensus. Further investigation and designing clinical trials are advisable to elucidate these aspects.

B-vitamin interventions for women and children in low-income populations.

PURPOSE OF REVIEW: This review examines the effect of B vitamins on women and child health from recent evidence available. RECENT FINDINGS: Findings were related to functional outcomes. In terms of foetal growth, although supplementation with B12 increased B12 status of nonpregnant and pregnant women and infants, maternal plasma homocysteine, which is related to multiple deficiencies of vitamin B12, B6, riboflavin or folate, has been shown to be associated with lower birth size rather than solely plasma B12. However, an experimental study with thiamine supplementation showed improvement in status in thiamine-deficient mothers and breast milk concentration, but not in infant status. Given the multiple aetiology of anaemia, the use of multiple micronutrient fortification has expectedly shown a reduction in anaemia prevalence in women. Furthermore, these micronutrients can interact with each other: high maternal folate intakes coupled with low B12 intakes were associated with a higher risk of delivering a small-for-gestational age infant. A high maternal plasma folate was also associated with insulin resistance in children aged 9.5 and 13.5 years. SUMMARY: Interventions with B vitamins were found to be efficacious in improving the status in women and children. In multiple micronutrient supplementation programmes, the optimum composition of the supplement needs to be determined. The deleterious effect of high folate intakes with low B12 intakes needs to be explored further.

Folic acid and vitamin B-12 supplementation and common infections in 6-30-mo-old children in India: a randomized placebo-controlled trial.

BACKGROUND: Young children in low- and middle-income countries frequently have inadequate vitamin B-12 (cobalamin) status. Poor folate status is also common and is associated with increased diarrheal and respiratory morbidity. OBJECTIVE: The objective was to measure the effect of folic acid and/or vitamin B-12 administration on the incidence of diarrhea and acute lower respiratory tract infections. DESIGN: One thousand North Indian children (6-30 mo of age) were enrolled in a randomized, double-blind, placebo-controlled trial to receive 2 times the Recommended Dietary Allowance of folic acid and/or vitamin B-12 or placebo daily for 6 mo. Children were individually randomly assigned in a 1:1:1:1 ratio in blocks of 16. Primary outcomes were the number of episodes of acute lower respiratory infections, diarrhea, and prolonged diarrhea. RESULTS: Folic acid and vitamin B-12 supplementation significantly improved vitamin B-12 and folate status, respectively. Neither folic acid nor vitamin B-12 administration reduced the incidence of diarrhea or lower respiratory infections. In comparison with placebo, children treated with folic acid alone or in combination with vitamin B-12 had a significantly higher risk of persistent diarrhea (OR: 2.1; 95% CI: 1.1, 3.8). CONCLUSIONS: Folic acid or vitamin B-12 supplementation did not reduce the burden of common childhood infections. In view of the increased risk of diarrhea, the safety of folic acid supplements in young children should be further assessed. This trial was registered at www.clinicaltrials.gov as NCT00717730 and at www.ctri.nic.in as CTRI/2010/091/001090.

Methoxistasis: integrating the roles of homocysteine and folic acid in cardiovascular pathobiology.

Over the last four decades, abnormalities in the methionine-homocysteine cycle and associated folate metabolism have garnered great interest due to the reported link between hyperhomocysteinemia and human pathology, especially atherothrombotic cardiovascular disease. However, clinical trials of B-vitamin supplementation including high doses of folic acid have not demonstrated any benefit in preventing or treating cardiovascular disease. In addition to the fact that these clinical trials may have been shorter in duration than appropriate for modulating chronic disease states, it is likely that reduction of the blood homocysteine level may be an oversimplified approach to a complex biologic perturbation. The methionine-homocysteine cycle and folate metabolism regulate redox and methylation reactions and are, in turn, regulated by redox and methylation status. Under normal conditions, a normal redox-methylation balance, or "methoxistasis", exists, coordinated by the methionine-homocysteine cycle. An abnormal homocysteine level seen in pathologic states may reflect a disturbance of methoxistasis. We propose that future research should be targeted at estimating the deviation from methoxistasis and how best to restore it. This approach could lead to significant advances in preventing and treating cardiovascular diseases, including heart failure.

Micronutrient deficiency and cognitive and physical performance in Indian children.

Several micronutrient deficiencies affect functional, particularly cognition and physical performance of children. Identifying and preventing sub-clinical deficiencies may be important so that adverse effects on functional performance by these deficiencies, particularly of iron and the B vitamins, are prevented. There is also the potential for childhood micronutrient deficiencies to have long-term effects that affect health and productivity in adulthood. This is especially relevant in a developing country such as India, which faces the dual burden of malnutrition and where the prevalence of these deficiencies is high. This review highlights the extent of micronutrient deficiencies in Indian children and focuses on the effect of deficiencies of the B vitamins and iron on cognitive and physical performance in children. Most studies on multiple micronutrient supplementation or fortification in Indian school children show modest effects on cognitive and physical performance, and it is relevant to point out that these studies have largely been conducted on urban children with mild deficiency at most; children with moderate or severe deficiency have not been studied. However, diets of rural children indicate large deficits in micronutrient intake, particularly of folic acid, riboflavin and iron, and their consequences have not been studied. With the limited evidence available, a short term but economical solution to ensure adequate micronutrient intakes could be through the fortification of staple cereals taken throughout the day. As increasing household incomes translate into an increase in food expenditure and diet diversification, it may become necessary to define upper limits of intake for nutrients in India, particularly as many commercial foods are fortified.

Nutrition and the psychoneuroimmunology of postpartum depression.

Postpartum depression (PPD) is a relatively common and often severe mood disorder that develops in women after childbirth. The aetiology of PPD is unclear, although there is emerging evidence to suggest a psychoneuroimmune connection. Additionally, deficiencies in n-3 PUFA, B vitamins, vitamin D and trace minerals have been implicated. This paper reviews evidence for a link between micronutrient status and PPD, analysing the potential contribution of each micronutrient to psychoneuroimmunological mechanisms of PPD. Articles related to PPD and women's levels of n-3 PUFA, B vitamins, vitamin D and the trace minerals Zn and Se were reviewed. Findings suggest that while n-3 PUFA levels have been shown to vary inversely with PPD and link with psychoneuroimmunology, there is mixed evidence regarding the ability of n-3 PUFA to prevent or treat PPD. B vitamin status is not clearly linked to PPD, even though it seems to vary inversely with depression in non-perinatal populations and may have an impact on immunity. Vitamin D and the trace minerals Zn and Se are linked to PPD and psychoneuroimmunology by intriguing, but small, studies. Overall, evidence suggests that certain micronutrient deficiencies contribute to the development of PPD, possibly through psychoneuroimmunological mechanisms. Developing a better understanding of these mechanisms is important for guiding future research, clinical practice and health education regarding PPD.

The role of B vitamins in the management of heart failure.

Heart failure (HF) is the leading cause of morbidity and mortality in industrialized countries, creating a significant burden on both the healthcare system and quality of life. Research efforts continue to explore new pharmaceutical or surgically based approaches to HF management, but the role of nutrition as an adjunct therapy has been largely ignored. Elderly age, anorexia, malabsorption, premature satiety, and disease severity are among the factors identified as contributing to reduced nutrient intakes in patients with HF. These factors suggest that patients with HF are at increased risk of multiple-nutrient deficiencies, including B vitamins. B vitamins may be of particular therapeutic interest because of their key roles as cofactors in energy-producing pathways. Recently, impaired stores of high-energy compounds have been linked with myocardial dysfunction and prognosis in patients with HF. Therefore, deficiencies of B vitamins might contribute to reduced energy stores and disease progression. This review summarizes the existing literature both with respect to the prevalence of B vitamin deficiency as well as evidence from supplementation trials in patients with HF. The findings suggest that most of the literature in this area has focused on thiamin deficiency in patients with HF, whereas other B vitamins remain largely unstudied. Although few sporadic trials suggest a role for B vitamins in the management of HF, none are conclusive. Therefore, there is a need for larger, more robust trials to assist in defining the B vitamin requirements as well as the impact of supplementation on both morbidity and mortality in patients with HF.

Adult-onset cerebral folate deficiency.

OBJECTIVE: To report new manifestations of cerebral folate deficiency, a rare metabolic autoimmune syndrome,in an adult. DESIGN: Case report. SETTING: University teaching hospital. PATIENT: A 58-year-old woman with progressive memory loss and myoclonus presented for medical attention. Results of cerebral spinal fluid analysis showed low levels of tetrahydrobiopterin and 5-methyltetrahydrofolate. The patient's serum folate level was normal. Serum contained folate receptor 1 blocking and binding antibodies. RESULTS: The patient was treated successfully with folinic acid supplementation, and after 6 months of treatment,clinical symptoms had resolved. CONCLUSIONS: To our knowledge, we report the first case of adult-onset cerebral folate deficiency. Furthermore, this condition could represent a treatable form of early-onset dementia.

Association of MTHFR and RFC1 gene polymorphism with hyperhomocysteinemia and its modulation by vitamin B12 and folic acid in an Indian population.

BACKGROUND/OBJECTIVES: 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. SUBJECTS/METHODS: Healthy population from four eastern states of India. Genotyping of SNPs, HPLC and chemiluminescence-based assay for homocysteine, vitamin B12 and folic acid. RESULTS: 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. CONCLUSIONS: 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.

Plasma choline concentration varies with different dietary levels of vitamins B6, B12 and folic acid in rats maintained on choline-adequate diets.

Choline is an important component of the human diet and is required for the endogenous synthesis of choline-containing phospholipids, acetylcholine and betaine. Choline can also be synthesised de novo by the sequential methylation of phosphatidylethanolamine to phosphatidylcholine. Vitamins B6, B12 and folate can enhance methylation capacity and therefore could influence choline availability not only by increasing endogenous choline synthesis but also by reducing choline utilisation. In the present experiment, we determined whether combined supplementation of these B vitamins affects plasma choline concentration in a rat model of mild B vitamin deficiency which shows moderate increases in plasma homocysteine. To this end, we measured plasma choline and homocysteine concentrations in rats that had consumed a B vitamin-poor diet for 4 weeks after which they were either continued on the B vitamin-poor diet or switched to a B vitamin-enriched diet for another 4 weeks. Both diets contained recommended amounts of choline. Rats receiving the B vitamin-enriched diet showed higher plasma choline and lower plasma homocysteine concentrations as compared to rats that were continued on the B vitamin-poor diet. These data underline the interdependence between dietary B vitamins and plasma choline concentration, possibly via the combined effects of the three B vitamins on methylation capacity.

[Wernicke's encephalopathy in chronic alcoholics]. / Wernicke-sjúkdómur medal áfengissjúkra.

Wernicke's encephalopathy (WE) is caused by thiamine (vitamin B1) deficiency and most commonly found in individuals with chronic alcoholism and malnutrition. Clinically, its key features are mental status disorders and oculomotor abnormalities as well as stance and gait ataxia. The diagnosis of WE is frequently missed although delay of appropriate treatment can lead to death or Korsakoff's amnestic syndrome. It is therefore crucial in suspected cases of WE, not to await confirmation of diagnosis, but immediately administer high-dose intravenous thiamine and simultaneously treat magnesium deficiency. Alcoholics at risk of WE should on admission receive immediate prophylactic therapy with parenteral thiamine.

Successful treatment of brain ischemia with supplementation therapy in a patient with hyperhomocysteinemia.

The effectiveness of homocysteine-lowering therapy on stroke prevention is still unclear. Although randomized controlled epidemiological trials have yielded mixed findings, a multicenter trial did not show any beneficial effect. Genetic studies are still lacking. Therefore, we report on a female patient with transient ischemic attacks and the thermolabile variant of methylenetetrahydrofolate reductase (TT genotype), who benefited from supplemental therapy for homocysteine lowering.