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Vitamin B12, Folic Acid, and the Immune System
Abstract
It is well established that poor nutrition can have a significant impact on immune system function. Chronic malnutrition is globally considered as a dominant cause of immune deficiency. A substantial proportion of the global population does not meet the recommended daily intake of nutrients. Chronic diseases can arise from even marginal deficiencies. A change in regulation of the immune system can arise from insufficient intake of micronutrients. In particular, there is evidence that folic acid (vitamin B9) and cobalamin (vitamin B12) play a crucial role in the healthy balance of the immune system. Inadequate levels of folic acid and B12 can drastically alter immune responses by affecting the production of nucleic acid, protein synthesis, inhibiting the activity of immune cells, and interfering with metabolic processes, including methylation and serine, glycine, and purine cycles. Inefficient methylation can lead to hyperhomocysteinemia which causes systemic and vascular inflammation contributing to the pathogenesis of many other diseases. Here we present the effects of folic acid and vitamin B12 on the immune system for health and disease.
... Consequently, deficiencies in these vitamins can compromise the renewal of epithelial linings and impair the proliferation and differentiation of immune cells. Specifically, deficiencies in folate and vitamin B12 increase susceptibility to infections by causing atrophy of lymphoid organs, including reduced cellularity in the thymus and bone marrow, as well as macroscopic alterations in epithelial tissues ( Figure 2) [82]. These deficiencies lead to a reduction in circulating lymphocyte counts, decreased proliferative capacity of T cells in response to mitogens and antigens, and diminished amounts of IL-2 and antibodies. ...
... Vitamin B12 plays a vital role in the conversion of methyl-tetrahydrofolate to tetrahydrofolate through a reaction catalyzed by the enzyme methionine synthase. A deficiency in vitamin B12 results in the accumulation of folic acid in its inactive form, methyl-tetrahydrofolate, which becomes trapped and cannot be reused, thus adversely affecting genetic material synthesis [82]. Both folate and vitamin B12 are required for the methylation of homocysteine to methionine in a reaction catalyzed by the enzyme methyl-tetrahydrofolate-homocysteine methyltransferase. ...
... High-risk groups include patients with metabolic diseases associated with obesity, vegans, and individuals with chronic gastrointestinal disorders. Collectively, current research suggests that vitamin B6 could be utilized as an anti-inflammatory nutrient, while supplementation with vitamin B12 and folates should be carefully considered in conditions with an inflammatory basis unless a lower plasma status is identified [82]. ...
Recent insights into the influence of nutrition on immune system components have driven the development of dietary strategies targeting the prevention and management of major metabolic-inflammatory diseases. This review summarizes the bidirectional relationship between nutrition and immunocompetence, beginning with an overview of immune system components and their functions. It examines the effects of nutritional status, dietary patterns, and food bioactives on systemic inflammation, immune cell populations, and lymphoid tissues, as well as their associations with infectious and chronic disease pathogenesis. The mechanisms by which key nutrients influence immune constituents are delineated, focusing on vitamins A, D, E, C, and B, as well as minerals including zinc, iron, and selenium. Also highlighted are the immunomodulatory effects of polyunsaturated fatty acids as well as bioactive phenolic compounds and probiotics, given their expanding relevance. Each section addresses the implications of nutritional and nutraceutical interventions involving these nutrients within the broader context of major infectious, metabolic, and inflammatory diseases. This review further underscores that, while targeted nutrient supplementation can effectively restore immune function to optimal levels, caution is necessary in certain cases, as it may increase morbidity in specific diseases. In other instances, dietary counseling should be integrated to ensure that therapeutic goals are achieved safely and effectively.
... Vitamin B12 is a cofactor for methionine synthase-important for catalyzing the formation of methionine from homocysteine-which is required to demethylate the inactive 5-methyl tetrahydrofolate to its active form tetrahydrofolate (THF) [126]. In cobalamin deficiency conditions, 5-methyl THF augmentation evokes a secondary folate deficiency affecting protein and DNA production as well as altering immune cell regulation and defense [85,127]. An inadequate amount of cobalamin can negatively affect folate functions, thereby inducing cobalamin deficiency that consequently promotes folate deficiency [128,129]. ...
... Pyridoxine, folate, and cobalamin are involved in maintaining and enhancing cytotoxic and killer cells [152]. In vitro and in vivo studies show that the metabolism of these vitamins is required for CD8 + T-cell proliferation and their effector functions [118,127,146,[153][154][155][156]. In contrast, a deficiency of these vitamins promotes DNA damage by arresting cell division at the S-phase and reduces cytotoxic cell expansion [153]. ...
... The mechanistic role of vitamin B6 in inducing T-cell subtype determination and inducing PD-1/PD-L1 blockage renders it a natural immunoregulator and a potential option for combination immunotherapy [271]. Comparably, PD-L1 expression is significantly reduced in the presence of vitamins B6 and B9 and thus, corresponded to reduced proliferation of pro-monocytic lymphoma cells in vitro [127]. Furthermore, Vitamin D supplementation can suppress tumor angiogenesis and induce anti-inflammatory effects within the tumor microenvironment, promoting apoptosis and autophagic death of tumor cells [272]. ...
Simple Summary
Despite clinical success, only a limited percentage of cancer patients are responsive to immunotherapy. Recently, gut microbiota modulation has been suggested as a tool to enhance immunotherapy efficacy, and mechanisms for these effects may be linked to microbial contributions—such as microbial-derived vitamins—to immune responses. While humans can acquire their vitamins from dietary sources, gut microbial-derived vitamins are crucial to the immune system’s function. The production of these vitamins can be altered by the bidirectional crosstalk between the immune system and the gut microbiome; however, their exact mechanism of action in bacterial communities and immune responses remains elusive. Further studies and clinical trials are needed to understand the role of microbial-derived vitamins in anti-tumor immune responses and their role in the efficacy of immunotherapies. This review will discuss the in-depth mechanisms of selective vitamins and their role in modulating immune responses, as well as their potential as immunotherapy enhancers.
Abstract
Not all cancer patients who receive immunotherapy respond positively and emerging evidence suggests that the gut microbiota may be linked to treatment efficacy. Though mechanisms of microbial contributions to the immune response have been postulated, one likely function is the supply of basic co-factors to the host including selected vitamins. Bacteria, fungi, and plants can produce their own vitamins, whereas humans primarily obtain vitamins from exogenous sources, yet despite the significance of microbial-derived vitamins as crucial immune system modulators, the microbiota is an overlooked source of these nutrients in humans. Microbial-derived vitamins are often shared by gut bacteria, stabilizing bioenergetic pathways amongst microbial communities. Compositional changes in gut microbiota can affect metabolic pathways that alter immune function. Similarly, the immune system plays a pivotal role in maintaining the gut microbiota, which parenthetically affects vitamin biosynthesis. Here we elucidate the immune-interactive mechanisms underlying the effects of these microbially derived vitamins and how they can potentially enhance the activity of immunotherapies in cancer.
... DLLME is a convenient way to measure low complexity matrices. For complex matrices, such as food and biological tissues, the development of vortexassisted dispersive liquid-liquid methods and ultrasound-assisted dispersive liquid-liquid methods for separation has been proposed (28)(29)(30)(31). DLLME techniques coupled with ultrasonic and vortex have been used as an effective method to prepare and separate samples. ...
... In particular, two important vitamins, namely FA and vitamin B 12 , are important for the healthy balance of the immune system (30). Vitamin B 12 deficiency increases homocysteine levels of serum. ...
... Studies show that vitamin B 12 reduces COVID-19 symptoms, such as oxygen and intensive care support (33,34). Inefficient vitamin B 12 deficiency causes systemic and vascular inflammation contributing to the pathogenesis of many other diseases (30). ...
Objectives
In this study, double-vortex-ultrasonic assisted dispersive liquid–liquid microextraction (DVUDLLME) was applied to determine the concentration of vitamin B9, 5-methyl tetrahydrofolate (5-MeTHF) and vitamin B12 in human serum samples.
Methods
High-performance liquid chromatography (HPLC) coupled with DVUDLLME was applied to analyze vitamins B in patients with Coronavirus disease (COVID-19). Then, significant variables were chosen and optimized using the hybrid Box–Behnken design and genetic algorithm.
Results
The detection limits of DVUDLLME–HPLC were 0.21 ng mL−1, 0.18 ng mL−1 and 55 pgmL−1 for vitamin B9, 5-MeTHF and vitamin B12, respectively. Subsequently, DVUDLLME-HPLC was applied to measure B vitamins and investigated their possible roles in susceptibility to COVID-19 infection. Fifty-seven percent of the patients without an underlying disease have significantly lower serum vitamin B12 levels in comparison to controls.
Conclusions
The advantages of this method are low detection limit, simple preparation, low retention time and the use of a cheaper technique instead of expensive mass detectors. The results suggest that vitamin B12 deficiency may decrease the immune system defenses against COVID-19 patients without an underlying disease and cause the disease to become severe. However, these works need a large population and further research, such as a randomized trial and a cohort study.
... Furthermore, it was found that FA significantly affects nucleic acid synthesis, DNA repair, cell growth, differentiation, apoptosis, cancer prevention (7), muscle development (8), and energy metabolism (9). In addition, FA plays a crucial role in the healthy balance of the immune system and plays a double-edged sword role in offspring health via mediating DNA methylation (10,11). Inadequate levels of FA can drastically alter immune responses (11). ...
... In addition, FA plays a crucial role in the healthy balance of the immune system and plays a double-edged sword role in offspring health via mediating DNA methylation (10,11). Inadequate levels of FA can drastically alter immune responses (11). It was also found that maternal FA deficiency changed the methylation of genes and pathways associated with neurodevelopment and learning/memory abilities in male rat offspring (12). ...
We previously observed the beneficial role of folic acid supplemented from maternal or offspring diet on lamb growth performance and immunity. Twenty-four Hu lambs from four groups (mother received folic acid or not, offspring received folic acid or not) were used in the current study, which was conducted consecutively to elucidate the molecular regulatory mechanisms of folic acid in lambs by analyzing blood metabolome, liver transcriptome, and muscle transcriptome. Serum metabolomics analysis showed that L-homocitrulline, hyodeoxycholic acid, 9-Hpode, palmitaldehyde, N-oleoyl glycine, hexadecanedioic acid, xylose, 1,7-dimethylxanthine, nicotinamide, acetyl-N-formyl-5-methoxykynurenamine, N6-succinyl adenosine, 11-cis-retinol, 18-hydroxycorticosterone, and 2-acetylfuran were down-regulated and methylisobutyrate was up-regulated by the feeding of folic acid from maternal and/or offspring diets. Meanwhile, folic acid increased the abundances of S100A12 and IRF6 but decreased TMEM25 in the liver. In the muscle, RBBP9, CALCR, PPP1R3D, UCP3, FBXL4, CMBL, and MTFR2 were up-regulated, CYP26B1 and MYH9 were down-regulated by the feeding of folic acid. The pathways of bile secretion, biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and herpes simplex virus 1 infection were changed by folic acid in blood, liver, or muscle. Further integrated analysis revealed potential interactions among the liver, blood, and muscle, and the circulating metabolites, hub gene, and pathways, which might be the predominant acting targets of folic acid in animals. These findings provide fundamental information on the beneficial function of folic acid no matter from maternal or offspring, in regulating animal lipid metabolism and immune enhancement, providing a theoretical basis for the use of folic acid from the view of animal health care.
... One recognized source of secondary aging in older persons is micronutrient deficiencies, resulting from some combination of malabsorption, low intake, and an increase in the aging body's requirements [193][194][195][196][197]. A dysregulation of essential nutrients, such as vitamin B 6 , vitamin B 12 , folic acid, and zinc, which are essential for cell-mediated immunity [198][199][200], are linked to various age-related pathologies and diseases, including inflammation [201,202], bone aging [203] and osteoporosis [204], and Alzheimer's disease [205,206], in addition to a decrease in NK cell count and/or cytotoxicity [197,[207][208][209]. ...
... Similarly, vitamin B 12 and folate (vitamin B9) dysregulation have been correlated with lower NK cell counts and activity, and can be improved through supplementation, which increases NK cell counts and activity in aging rats [200,209]. Again, a nutritional formula containing 120 IU vitamin E, 3.8 µg vitamin B 12 , 400 µg folic acid, and other nutrients increased the NK activity relative to the placebo in healthy subjects aged 70 years and older [212]. ...
Aging is the greatest risk factor for nearly all major chronic diseases, including cardiovascular diseases, cancer, Alzheimer’s and other neurodegenerative diseases of aging. Age-related impairment of immune function (immunosenescence) is one important cause of age-related morbidity and mortality, which may extend beyond its role in infectious disease. One aspect of immunosenescence that has received less attention is age-related natural killer (NK) cell dysfunction, characterized by reduced cytokine secretion and decreased target cell cytotoxicity, accompanied by and despite an increase in NK cell numbers with age. Moreover, recent studies have revealed that NK cells are the central actors in the immunosurveillance of senescent cells, whose age-related accumulation is itself a probable contributor to the chronic sterile low-grade inflammation developed with aging (“inflammaging”). NK cell dysfunction is therefore implicated in the increasing burden of infection, malignancy, inflammatory disorders, and senescent cells with age. This review will focus on recent advances and open questions in understanding the interplay between systemic inflammation, senescence burden, and NK cell dysfunction in the context of aging. Understanding the factors driving and enforcing NK cell aging may potentially lead to therapies countering age-related diseases and underlying drivers of the biological aging process itself.
... Similarly, findings showed that TNF-α production has increased in the spinal cords vitamin B 12 -deficient rats, whereas TNF-α synthesis was elevated in the macrophages of vitamin B 12 -deficient mice [76]. Furthermore, due to glycoprotein 130 (gp130) dysregulation, vitamin B 12 -deficient animals demonstrated reduced IL-6 production [76]. ...
... Similarly, findings showed that TNF-α production has increased in the spinal cords vitamin B 12 -deficient rats, whereas TNF-α synthesis was elevated in the macrophages of vitamin B 12 -deficient mice [76]. Furthermore, due to glycoprotein 130 (gp130) dysregulation, vitamin B 12 -deficient animals demonstrated reduced IL-6 production [76]. ...
Food components have long been recognized to play a fundamental role in the growth and development of the human body, conferring protective functionalities against foreign matter that can be severe public health problems. Micronutrients such as vitamins and minerals are essential to the human body, and individuals must meet their daily requirements through dietary sources. Micronutrients act as immunomodulators and protect the host immune response, thus preventing immune evasion by pathogenic organisms. Several experimental investigations have been undertaken to appraise the immunomodulatory functions of vitamins and minerals. Based on these experimental findings, this review describes the immune-boosting functionalities of micronutrients and the mechanisms of action through which these functions are mediated. Deficiencies of vitamins and minerals in plasma concentrations can lead to a reduction in the performance of the immune system functioning, representing a key contributor to unfavorable immunological states. This review provides a descriptive overview of the characteristics of the immune system and the utilization of micronutrients (vitamins and minerals) in preventative strategies designed to reduce morbidity and mortality among patients suffering from immune invasions or autoimmune disorders.
... In the context of our study where supplementation was paralleled with a decrease in B memory, CD4 T memory, T-regulatory, and CD8T cells, it is plausible that astragaloside and Rutin, along with other ingredients found in Cel system may also be acting collectively to regulate immune function, potentially reducing excessive immune activity and chronic inflammation [59,60]. Zinc, Selenium, and vitamin B12 have all been proven to modulate inflammation and dampen immune responses, mirroring the alterations observed in immune cell proportions [61][62][63]. The maintenance of cellular integrity and homeostasis highly depends on a balanced immune response. ...
... [1] Adequate Vitamin B12 also helps to maintain inflammatory cytokines, reduces the risk of cardiovascular diseases, [2] and boosts the immune system. [3] Vitamin B12 deficiency can cause anemia, poor memory, depression and various ailments associated with nerve damage such as numbness and paresthesia in hands and feet. The prevalence of Vitamin B12 deficiency leads the physicians to prescribe it to their patients empirically, resulting in its high level in blood. ...
Vitamin B12 (Cobalamin or Cbl) plays a crucial role in normal human growth and development, as well as in neurological, cardiovascular, and immune systems. Previous studies reported association of high levels of cobalamin with solid cancers, hematological disorders, and liver diseases. Reporting the frequency of comorbid diseases with high serum Vitamin B12 level in patients attending KSAMC at Madinah
... [1] Adequate Vitamin B12 also helps to maintain inflammatory cytokines, reduces the risk of cardiovascular diseases, [2] and boosts the immune system. [3] Vitamin B12 deficiency can cause anemia, poor memory, depression and various ailments associated with nerve damage such as numbness and paresthesia in hands and feet. The prevalence of Vitamin B12 deficiency leads the physicians to prescribe it to their patients empirically, resulting in its high level in blood. ...
Objectives
Vitamin B12 (Cobalamin or Cbl) plays a crucial role in normal human growth and development, as well as in neurological, cardiovascular, and immune systems. Previous studies reported association of high levels of cobalamin with solid cancers, hematological disorders, and liver diseases. Reporting the frequency of comorbid diseases with high serum Vitamin B12 level in patients attending KSAMC at Madinah.
Methods
This is a retrospective, cross-sectional study on data collected during 1 year (May 2022–May 2023) from 3511 report, patients with high cobalamin blood level (normal upper limit 771 pg/mL) as determined in our laboratory on COBAS® were included. Patient’s clinical diagnosis, medication history and other laboratory parameters performed were also checked for disease comorbidities.
Results
Our results revealed statistically significant increase in serum Vitamin B12 in patients with diabetes mellitus, with the use of this vitamin as supplement therapy 53.2% (the predominant comorbidity), together with liver, blood, chest, kidney, thyroid and neurological diseases, and various solid tumors. A positive correlation was found between serum Vitamin B12, age and laboratory parameters including aspartate aminotransferase, gamma-glutamyl transferase, and direct bilirubin, and a negative correlation was seen between serum Vitamin B12 level, serum albumin (ALB), red blood cell count, hemoglobin, and free T3 (FT3). While, no significant correlation with the rest of the checked parameters was detected.
Conclusion
This study found high serum level of Vitamin B12 associated with various disease entities, for example, (diabetes mellitus treated with Vitamin B12 as supplement therapy, liver, blood, chest, kidney, thyroid, neurological diseases, and various solid tumors), so when Vitamin B12 is high, further investigations will be recommended. Most of the comorbidities were benign in Saudis, followed by Egyptians with predominance of female-aged 50–70 year old.
... Iron can play an important role in the immune response and adequate iron intake is essential to healthy innate and adaptive responses maintenance [50]. The other two nutrients involving in immune function are folic acid and cobalamin [29]. As previously mentioned, in the present study, there was an association between lower intakes of vitamin B9 and B12 and the higher uPDI scores. ...
Background
The fast spread of the coronavirus disease 2019 (COVID-19) epidemic and its high mortality were quickly considered by the health community. Dietary patterns play an important role in strengthening or weakening the immune system and thus incidence of diseases.
Aim
The present study can provide a comprehensive picture of the association between adherence to unhealthy plant-based diet (uPDI) and COVID-19 incidence.
Methods
This study was undertaken on 8157 adults’ participants of the Yazd Health Study (YaHS) and Taghzieh Mardom-e-Yazd (TAMIZ) study aged 20 to 70 years. Data on dietary intakes were obtained using a validated food frequency questionnaire (FFQ). Multivariable logistic regression analysis was used to assess the association between uPDI and COVID-19.
Results
We found a significant association between uPDI and the risk of COVID-19 (OR: 1.36; 95% CI: 1.05–1.75) in the crude model. After adjusting potential confounders, a significant increasing trend in the odds of COVID-19 across increasing quintiles of uPDI (OR: 1.58;95% CI: 1.05–2.37; P-value: 0.027) was observed. Stratified analysis based on sex indicated that uPDI significantly increased the risk of COVID-19 only in males (OR: 1.73;95% CI: 1.12–2.67; P-value: 0.012) and had no effect on females.
Conclusions
Participants in the highest quintiles of the uPDI had 58% higher odds of COVID-19 compared to subjects in the lowest quintile of uPDI. Although our study has promising results, stronger clinical studies are needed.
... In the context of our study where supplementation was paralleled with a decrease in B memory, CD4 T memory ,T-regulatory, and CD8T cells, it is plausible that astragaloside and rutin, along with other ingredients found in Cel system may also be acting collectively to regulate immune function, potentially reducing excessive immune activity and chronic inflammation [59,60]. Zinc, Selenium and vitamin B12 have all been proven to modulate inflammation and dampen immune responses, mirroring the alterations observed in immune cell proportions [61][62][63].The maintenance of cellular integrity and homeostasis highly depends on a balanced immune response. All metabolic and proteomic biomarker changes following Cel system supplementation further underscore the ability of its active ingredients to target intricate molecular and cellular processes, pivotal for maintaining metabolic homeostasis and reducing the burden of age-related oxidative damage and chronic inflammation. ...
Aging interventions have progressed in recent years due to the growing curiosity about how lifestyle impacts longevity. This study assessed the effects of SRW Laboratories Cel1, Cel2, and Cel3 (Cel System) nutraceutical range on epigenetic methylation patterns, inflammation, physical performance, body composition, and epigenetic biomarkers of aging. A 1-year study was conducted with 51 individuals, collecting data at baseline, 3 months, 6 months, and 12 months. Participants were encouraged to walk 10 minutes and practice 5 minutes of mindfulness daily. Significant improvements in muscle strength, body function, and body composition metrics were observed. Epigenetic clock analysis showed a decrease in biological age with significant reductions in stem cell division rates. Immune cell subset analysis indicated significant changes, with increases in eosinophils and CD8T cells and decreases in B memory, CD4T memory, and T-regulatory cells. Predicted epigenetic biomarker proxies (EBPs) showed significant changes in retinol/TTHY, a regulator of cell growth, proliferation, and differentiation, and deoxycholic acid glucuronide levels, a metabolite of deoxycholic acid generated in the liver. Gene ontology analysis revealed significant CpG methylation changes in genes involved in critical biological processes related to aging, such as oxidative stress-induced premature senescence, pyrimidine deoxyribonucleotide metabolic process, TRAIL binding, hyaluronan biosynthetic process, neurotransmitter loading into synaptic vesicles, pore complex assembly, collagen biosynthetic process, protein phosphatase 2A binding activity, and activation of transcription factor binding. Our findings suggest that the Cel System supplement range may effectively reduce biological age and improve health metrics, warranting further investigation into its mechanistic pathways and long-term efficacy.
... SP is rich in vitamin B12, γ-linolenic fatty acid, β-carotene, calcium, and iron [3,4], making it an attractive option for supplementing animal diets. Vitamin B12 is crucial for red blood cell formation and immunological function, while γlinolenic fatty acid helps maintain cell membrane integrity and produces anti-inflammatory eicosanoids [5,6]. β-carotene, a precursor to vitamin A, is vital for vision, immune function, and skin health [7]. ...
Enhancing the sustainability of chicken farming involves improving health and productivity and product qualities. This study explores the influence of Spirulina platensis (SP) supplementation on the productivity, egg quality, shelf life during storage, and blood biochemistry of laying hens. A total of 192 thirty-nine-week-old White Leghorn hens were randomly divided into 4 dietary groups: a control group and 3 treatment groups receiving 2.5 g/kg, 5 g/kg, or 10 g/kg of SP, respectively. The study was conducted for six weeks with measuring feed intake, feed conversion ratio, egg production, egg quality, shelf life, and blood biochemistry. The results demonstrated significant enhancements in egg weight (p < 0.05) and egg mass (p < 0.05) in the treatment of SP groups. The SP treated hens showed significant improvements in yolk color (p < 0.05) and Haugh unit scores (p < 0.05). The SP supplementation showed a hepatoprotective effect, as indicated by significant reduction in Alanine aminotransferase (ALT) (p < 0.05) and alkaline phosphatase (ALP) (p < 0.05) levels; however, increases in total protein, albumin, and globulin levels were observed. Furthermore, the egg quality of stored eggs for 21 days linearly increased with increments in the SP levels. In conclusion, it can be speculated that adding SP at 2.5 g/kg and 5 g/kg can significantly improve the productivity of laying hens, eggs’ quality, shelf life, and blood biochemistry, thereby contributing to a more sustainable and efficient chicken production.
... This protein has been broadly adopted due to its distinctive properties, encompassing antioxidation, immunological modulation, and lipid control (Hassan et al., 2022;Sinha et al., 2022;Bakr et al., 2023;Saad et al., 2023). Vitamin B12 (cobalamin) has also been widely utilized for its therapeutic potential, especially when conjugated with target proteins, supporting the immune system (Todorova et al., 2017;Mikkelsen & Apostolopoulos, 2019;van de Lagemaat et al., 2019;Peterson et al., 2020). Recently, a combination of these two potent therapies has been explored in some studies, presenting an effective compound with antioxidant and immune system modulation capabilities (Guo et al., 2018(Guo et al., , 2019(Guo et al., , 2022Wu et al., 2021). ...
The escalating use of nanodiamonds (NDs) has raised concerns about their ecotoxicological impact, prompting exploration of therapeutic interventions. This paper pioneers the examination of Vitamin B12‐conjugated sericin (VB12‐SER) as a potential therapeutic approach against ND‐induced toxicity in darkling beetles ( Blaps polychresta ). The study analyzes mortality rates and organ‐specific effects, covering the testis, ovary, and midgut, before and after treatments. Following exposure to 10 mg NDs/g body weight, within a subgroup of individuals termed ND2 with a mortality rate below 50%, two therapeutic treatments were administered, including pure sericin (SER) at 10 mg/mL and VB12‐SER at 10.12 mg/mL. Consequently, five experimental groups (control, SER, ND2, ND2+SER, ND2+SER+VB12) were considered. Kaplan–Meier survival analysis was performed to assess the lifespan distribution of the insects in these groups over a 30‐d period. Analyses revealed increased mortality and significant abnormalities induced by NDs within the examined organs, including cell death, DNA damage, enzyme dysregulation, antioxidant imbalances, protein depletion, lipid peroxidation, and morphological deformities. In contrast, the proposed treatments, especially (ND2+SER+VB12), demonstrated remarkable recovery, highlighting VB12‐conjugated SER's potential in mitigating ND‐triggered adverse effects. Molecular docking simulations affirmed binding stability and favorable interactions of the VB12‐SER complex with target proteins. This research enhances understanding of NDs’ effects on B. polychresta , proposing it as an effective bioindicator, and introduces VB12‐conjugated SER as a promising therapeutic strategy in nanotoxicological studies.
... Vitamin B 12 plays a vital role in the immune system healthy balance and DNA synthesis. It has a leading role in the nervous system function that maintenance nerve cell and cooperating with cell synthesis in addition the catabolism of proteins and fatty acids [16,17]. ...
Background
Vitamin B 12 is a very important water-soluble vitamin, which was first isolated from the liver as an anti-pernicious anemia factor. The sole source of vitamin B 12 is the animal-based food. It has a complicated structure and requires expensive multi-steps to be synthesized chemically. Intriguingly, vitamin B 12 can be produced through microbial fermentation by microorganisms in a cheap and more effective manner.
Objective
This study aims to isolate and characterize microorganisms that have the capability to produce vitamin B 12 . In addition, the current work aims to optimize the vitamin B 12 production conditions by isolating strains using suitable waste materials to obtain a high vitamin B 12 yield.
Materials and methods
Different bacterial and yeast isolates were isolated from marine and food samples using the pour-plate technique. These isolates were screened for vitamin B 12 production using a specific growth medium that lacked vitamin B 12 and a test indicator bacterium. The content of vitamin B 12 was estimated using spectrophotometer measurement and high-performance liquid chromatography (HPLC). The isolates that showed high vitamin B 12 productivity were identified using MALDI-TOF technique. The identified strains were implemented for the optimization of vitamin B 12 production to reveal the most proper and optimum conditions for the production. Response surface methodology (RSM) was employed to enhance the production of vitamin B 12 in a flask scale. Agro-industrial wastes such as molasses were used for vitamin B 12 production using the most optimum conditions as determined by RSM.
Results and conclusion
Eighty-seven actinomycetes, bacterial, and yeast isolates were screened for vitamin B 12 production. Out of these isolates, 15 showed high vitamin B 12 productivity. We found that bacilli and yeast isolates were the most productive among the tested cocci and actinomycetes isolates. The highly productive Bacillus and yeast isolates were identified using the MALDI-TOF analysis. The isolates were identified as Candida pelliculosa , Geotrichum candidum , Bacillus subtilis and Bacillus sp . One strain of Candida pelliculosa (coded BYI), three strains of Geotrichum candidum (coded as MZYC, MZYD, and MZYG) were selected for studying the effect of sugar type and inoculum size on the yield of vitamin B 12 production. Strain MZYD was selected for the statistical modelling using RSM to optimize seven factors for the vitamin B 12 production. These factors included temperature, fermentation time, salt concentration, pH, sugar concentration, inoculum size, and aeration. Five factors i.e ., temperature, pH, sugar concentration, and inoculum size were shown to significantly improve the vitamin B 12 production. A maximum yield of 64.21 μg/100 ml was obtained using the optimized RSM conditions. These optimized conditions were used to produce vitamin B 12 using molasses as a raw material for the microbial growth.
... FA plays important roles in many intracellular processes, including nucleic acid and protein synthesis (Liu and Ward, 2010;Ratajczak et al., 2021), gene expression (Bailey and Gregory, 1999), and AA production (Ntaios, 2015). Inadequate intake of micronutrients by the organism (e.g., FA and vitamin B 12 ) can disrupt metabolism and immune homeostasis (Mikkelsen and Apostolopoulos, 2019). Physiological research on dietary FA in fish suggests that FA is required for the healthy growth of juvenile tilapia and can significantly increase body weight (Hang et al., 2022). ...
Folic acid (FA) is an essential vitamin for the growth and health of aquatic organisms in the aquaculture industry. The purpose of this study was to investigate the effects and potential mechanisms of action of dietary FA on the growth and immune response of red swamp crayfish (Procambius clarkii). Crayfish (n = 360; 3 tanks of 20 crayfish for each dietary treatment) were fed diets containing different levels of FA (0 [control], 0.5, 1, 2, 4, and 8 mg/kg dry feed weight) for 60 d. Broken-line analysis based on the final weight and specific growth rate revealed that the optimal dietary FA level for promoting growth was 2 mg/kg. Villus length, lipase activity, and antioxidant superoxide dismutase activity significantly increased under the 2 mg/kg treatment. Transcriptome analysis identified 177 upregulated and 298 downregulated differentially expressed genes (DEGs) between the 0 (control) and 2 mg/kg groups. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the most significantly enriched pathways were related to glucose metabolism. Among the DEGs involved in glucose metabolism, Tpi1 (triosephosphate isomerase 1) and Pck1 (phosphoenolpyruvate carboxykinase 1) were upregulated and downregulated under FA treatment, respectively. Our findings suggest that the optimal dietary FA requirement for crayfish is 2 mg/kg and that dietary FA may enhance nutrient bioavailability and regulate glucose metabolism to improve crayfish growth performance.
... 5 Both cell-mediated and humoral immunity are affected in folate and vitamin B12 deficiency states. 6 Overall, the deficiency of either folate or B12 leads to an increase in Hcy, a sulfur amino acid. In high levels, it exerts deleterious effects on the vascular endothelium and induces excitotoxic effects in immune-competent cells. ...
Objective
We aimed to review the available evidence on the association between vitamin B12, folate, and homocysteine levels with worse outcomes among COVID-19 patients.
Methods
The search was carried out in ten databases simultaneously run on 10 May 2023, without language restrictions. We included cross-sectional, case-control, and cohort studies. The random-effects meta-analysis was performed using the Sidik-Jonkman method and corrected 95% confidence intervals using the truncated Knapp-Hartung standard errors. Standardized mean difference and 95% CI was used as the measure effect size.
Results
Thirteen articles were included in this review (n = 2134). Patients with COVID-19 who did not survive had the highest serum vitamin B12 values (SMD: 1.05; 95% CI: 0.31–1.78; p = 0.01, I² = 91.22%). In contrast, low serum folate values were associated with patients with severe COVID-19 (SMD: −0.77; 95% CI: −1.35 to −0.19; p = 0.02, I² = 59.09%). The remaining tested differences did not yield significant results.
Conclusion
Elevated serum levels of vitamin B12 were associated with higher mortality in patients with COVID-19. Severe cases of COVID-19 were associated with low serum folate levels. Future studies should incorporate a larger sample size.
... While moderate alcohol consumption may not have as pronounced adverse effects, maintaining a healthy lifestyle with moderation in alcohol intake is advisable to support overall immune function and well-being. 23,24 Research by Yamamoto et al. stated that there was a negative correlation between spiked IgG levels and weekly alcohol consumption. 25 The Covid-19 has affected human life in various aspects, both individually (various kinds of fears such as fear of illness and death) and socially (economic recession, limited education and work, and corona phobia). ...
Background: Non-communicable diseases (NCDs) have been identified as predictors of the severity of Coronavirus Disease 2019 (Covid-19). Some factors like smoking, alcohol consumption, and physical inactivity, which are associated with NCDs, may potentially hinder the efficacy of vaccines, reducing their ability to prevent the severity and complications of infectious diseases such as the Covid-19. Objective: This study investigated the NCD, risk factors associated with the levels of quantitative antibodies after the second Covid-19 vaccination.Methods: A cross-sectional study was conducted at a Covid-19 vaccination centre in Jakarta. Ninety subjects, aged ≥18, completed demographic and NCDs risk factor questionnaires. Blood samples were collected and analysed by using the electro chemiluminescence immunoassay analyser (ECLIA) method to measure quantitative antibody levels 30 days after 2nd Covid-19 vaccination. The bivariate analysis was performed to explore associations among the variables. The logistic regression was subsequently performed to identify the factors that remained independent in influencing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody status. Results: The mean value of antibody level in this study was 191 U/ml. The results indicated that 35.5% (n=32) of respondents had SARS-CoV-2 antibody levels below average. The regression results suggested that the odds of having higher antibody levels were reduced for individuals with hypertension (Adjusted Odd Ratio [AOR] = 0.74, p value = 0.022), diabetes (AOR = 0.82, p value = 0.038) comorbidities accompanied with smoking (AOR = 0.55, p value = 0.044), drinking alcohol (AOR = 0.92, p value = 0.030), and low physical activity levels (AOR = 0.67, p value = 0.043). Conclusion: The study found that 35.5% of participants had SARS-CoV-2 antibody levels below the average. Factors such as hypertension, diabetes, comorbidities with smoking, alcohol consumption, and low physical activity were associated with reduced odds of higher antibody levels.
... 43 Additionally, it has been observed that low levels of folic acid and vitamin B12 can significantly influence immunological responses by altering protein and nucleic acids synthesis, stifling the activity of immune cells and interfering with metabolic processes. 44 L-lysine aids in the production of enzymes, antibodies and hormones, lowers anxiety, prevents cold sores, improves calcium, iron and zinc absorption, promotes wound healing and collagen formation, and supports the immune system. 45 Collagen is a crucial protein that plays a role in wound healing, and lysine is necessary for its synthesis. ...
Background: Vitamin B-complex aids in the development and maintenance of a healthy immune system and also helps to prevent or lessen various infections, especially cases of acute sickness like fever. This study investigates the opinions and experiences of doctors about the effectiveness and usefulness of the targeted vitamin B-complex combinations comprising of pyridoxine hydrochloride, cyanocobalamin, nicotinamide, chromium chloride, sodium selenite, L-lysine in hastening the recovery from acute diseases like fever and others. It offers insight on the perceived advantages, disadvantages and general efficacy of target vitamin B-complex combinations in comparison to other current medications by assessing doctors' preferences, clinical observations and patient outcomes. Additionally, the study also outlines the role of selenium, chromium and L-lysine aiding in the faster recovery along with the targeted vitamin B-complex combination. Studies show that selenium supplementation can reduce mortality rates in viral infections, improve recovery rates in COVID-19 patients and improve the recovery rate. Chromium offers antioxidant properties, and influences immune response and hence helps in the faster recovery of several acute illnesses. Lysine serves as a pivotal building block for proteins, which in turn contribute significantly to the growth and restoration of bodily tissues following damage. Methods: The study was a retrospective study in July 2023 used a questionnaire-based survey to assess the efficacy and tolerability of vitamin B-complex combinations for faster recovery in acute illnesses, focusing on fever. The study used a validated questionnaire with 13 questions, and data was entered into asoftware database. Complete cases were analyzed, and missing data was excluded due to low occurrence. The final report was prepared after cleaning the data. Result: The study included 132 doctors from various medical specializations aimed to understand their perception and experience of using vitamin B-complex for faster recovery from acute illnesses. The most important factor contributing to choosing vitamin B-complex was the uses of micronutrients, which help produce red blood cells (40.2%), followed by use in treating mouth ulcers (31.1%) and are critical for pregnant ladies (28.8%). Antioxidants like selenium and chromium were found to be significantly effective (57.6%) for faster recovery in acute illnesses, while 39.4% considered them moderately effective. The study revealed that 88.6% of doctors considered the use of vitamin B-complex combination advantageous due to the presence of folic acid, L-lysine and selenium, and that 97.7% of doctors had a positive attitude about continuing to prescribe vitamin B-complex supplementation in the future. The study found that the current vitamin B-complex combination outperforms its competitors mostly (82%), especially in helping to recover from acute illnesses faster. It was also found to be friendly for the elderly, as no side effects were observed. Conclusion: Results suggest that the targeted vitamin B-complex combination can improve acute disease management and help health care professionals make informed decisions for optimal well-being. The findings contribute to a deeper understanding of the medical decisionmaking process and the nuanced considerations that impact the prescription of specific treatment options for acute illnesses.
... Inadequate levels of vitamin B 12 and folic acid (necessary for DNA synthesis) can dramatically alter immune responses by affecting the production of nucleic acid and protein synthesis, inhibiting the activity of immune cells, and interfering with metabolic processes, such as methylation and serine, glycine, and purine cycles. Inefficient methylation can lead to hyperhomocysteinemia which causes systemic and vascular inflammation, contributing to the pathogenesis of many other diseases [44]. Several studies have shown that high levels of homocysteine and low levels of vitamin B 12 and folate are associated with an increased risk of developing Alzheimer's disease [45,46]. ...
Simple Summary
Cobalt (Co) is an essential element with ubiquitous dietary exposure and possible incremental exposure due to dietary supplements, occupations, and medical devices. The main function of Co in humans is based on its role in vitamin B12 (cobalamin). This review provides an extended overview of Co in relation to its effects on health and biological processes.
Abstract
Cobalt (Co) is an essential trace element for humans and other animals, but high doses can be harmful to human health. It is present in some foods such as green vegetables, various spices, meat, milk products, seafood, and eggs, and in drinking water. Co is necessary for the metabolism of human beings and animals due to its key role in the formation of vitamin B12, also known as cobalamin, the biological reservoir of Co. In high concentrations, Co may cause some health issues such as vomiting, nausea, diarrhea, bleeding, low blood pressure, heart diseases, thyroid damage, hair loss, bone defects, and the inhibition of some enzyme activities. Conversely, Co deficiency can lead to anorexia, chronic swelling, and detrimental anemia. Co nanoparticles have different and various biomedical applications thanks to their antioxidant, antimicrobial, anticancer, and antidiabetic properties. In addition, Co and cobalt oxide nanoparticles can be used in lithium-ion batteries, as a catalyst, a carrier for targeted drug delivery, a gas sensor, an electronic thin film, and in energy storage. Accumulation of Co in agriculture and humans, due to natural and anthropogenic factors, represents a global problem affecting water quality and human and animal health. Besides the common chelating agents used for Co intoxication, phytoremediation is an interesting environmental technology for cleaning up soil contaminated with Co. The occurrence of Co in the environment is discussed and its involvement in biological processes is underlined. Toxicological aspects related to Co are also examined in this review.
... According to Gevi et al. (18), vitamin B6 deficiency slows the transformation of the excitatory amino acid glutamate into the inhibitory neurotransmitter gamma-aminobutyric acid, which may play an important role in the induction of hyperactivity and hyperexcitability symptoms in children with ASD. In addition, biochemical alterations can adversely affect the development and functioning of a child's immune system, contributing to the development of immunodeficiency and related immune dysregulation, which can mediate a number of severe immune-dependent complications in the pathogenesis of encephalopathy in children with ASD (30,31). As noted in the results of a systematic review by Mikkelsen et al. (30), deficiency of vitamin B12 and folic acid in humans can induce lymphopenia, changes in the level of CD4/CD8 index, impaired proliferation of T-and B-lymphocytes, decreased number and weakening of the functional activity of natural killer cells and neutrophils, which leads to the formation of secondary immunodeficiency. ...
Introduction: the results of 5 randomized controlled meta-analysis studies showed the association between genetic deficiency of folate cycle and autistic spectrum disorders in children. The purpose of the present study is to investigate the biochemical alterations in children with autism spectrum disorders associated with genetic deficiency of the folate cycle. Methods: the experimental group involved 225 children diagnosed with autism spectrum disorders (Diagnostic and Statistical Manual of Mental Disorders IV-TR, International Statistical Classification of Diseases and Related Health Problems 10), who suffered from a genetic deficiency of the folate cycle (methylenetetrahydrofolate reductase C677T + methylenetetrahydrofolate reductase A1298C and/or methionine synthase A2756G and/or methionine synthase reductase A66G; polymerase chain reaction). The control group included 51 healthy children who followed the same age and gender distribution pattern of the patients group. Results: the study revealed that the patients had a specific pattern of biochemical alterations in serum (p˂0.05; Z˂Z0.05). Mean value and (SD) are reported. Hyperhomocysteinemia: 9.63 (5.36) μmol/L, r.v. ˂5.2); deficiencies of vitamins: B6 [6.32 (3.58) μg/L, r.i. 8.7-27.2], folic acid [2.97 (6.85) pg/mL, r.i. 3.89-26.8], B12 [112.64 (374.2) pg/mL, r.i. 197-771], and D3 [13.98 (20.41) ng/mL, r.i. 30-60]; hypercreatininemia [69.13 (64.21) μmol/L, r.i. 3 years: 21-36, 3-5 years: 27-42, 5-8 years: 28-50], increased creatine kinase [314.12 (443.42) U/L, r.i. 39-308 U/L]; and lactate dehydrohenase [378.47 (443.72) U/L, r.i.135-225]. At the time of examination, an increase in the serum concentration of homocysteine was registered in 88% of the patients. The associations between different folate cycle genes polymorphisms with certain biochemical abnormalities were shown Discussion: autism spectrum disorders associated with genetic deficiency of the folate cycle in children are characterized by a specific pattern of biochemical changes that is not found in healthy children and may be involved in the pathogenesis of immunodeficiency and encephalopathy. These data can be used in clinical practice for diagnostic purposes to identify a subgroup of children with autism spectrum disorders associated with genetic folate cycle deficiency and for the selection of biochemical correction during treatment.
... Vitamin B12 is essential for the appropriate functioning of the immune system and its deficiency is associated with an alteration in the methylation reactions leading to an increase in the levels of homocysteine in the body, which in turn favors immune dysfunction [144,145]. All foods of animal origin are good sources of vitamin B12, including meat, fish, eggs, dairy products, and poultry. ...
Autoimmune thyroid diseases are on the rise worldwide, and such a rapid increase is mainly driven by environmental factors related to changed lifestyles in “modern” societies. In this context, diet seems to play a crucial role. An unhealthy high-energy diet, rich in animal fat and proteins, salt and refined sugars (the so-called “Western diet”) negatively influences the risk of autoimmunity by altering the immune balance and the gut microbiota composition, enhancing oxidative stress and promoting inflammation. In contrast, the Mediterranean diet represents a unique model of healthy eating, characterized by a high intake of food from vegetable sources, a low consumption of saturated fats in favor of unsaturated fats (mainly, olive oil), a moderate consumption of fish (typically, the small oily fishes) and dairy products, as well as a moderate consumption of wine at meals, and a low intake of meat. Thanks to its nutritional components, the Mediterranean Diet positively influences immune system function, gut microbiota composition, and redox homeostasis, exerting anti-oxidants, anti-inflammatory, and immunomodulatory effects. The present review was aimed at exploring the existing knowledge on the correlations between dietary habits and thyroid autoimmunity, to evaluate the role of the Mediterranean diet as a protective model.
... A deficiency of micronutrients can suppress immunity by affecting the innate immune response, T cells and adaptive immune response resulting in an imbalance (12). One of the micronutrients that can be used to improve the work and response of the body's immunity is the provision of vitamin intake (13). Inadequate vitamin intake can lead to suppression of the immune system and can increase the risk of infection. ...
Introduction: Tuberculosis (TB) is a wasting or consumption disease which causes metabolic changes in tuberculosis patients. The metabolic changes that can occur are decreased appetite, micronutrient malabsorption, and malnutrition. The purpose of this research was to determine the differences in the result of an oral combination of vitamins B1, B6, and B12 supplementations on Interferon Gamma (IFN-γ) levels and CD4+ T-cell counts in pulmonary tuberculosis patients receiving first-line Opioid Agonist Therapy (OAT) compared to only OAT therapy.
... cg07077240 is located in the HERC3 gene, that negatively regulates the NF-Kb pathway which is an important activator of inflammatory and immune reactions [55]. Folate is a vital nutrient for regulation of the immune reaction and inflammatory response [56]. Therefore, methylation at these CpG sites could potentially play a role in inflammatory related processes associated with folate. ...
Aim: To perform an epigenome-wide association study (EWAS) of serum folate in maternal blood. Methods: Cross-ancestry (Europeans = 302, South Asians = 161) and ancestry-specific EWAS in the EPIPREG cohort were performed, followed by methyl quantitative trait loci analysis and association with cardiometabolic phenotypes. Replication was attempted using maternal folate intake and blood methylation data from the MoBa study and verified if the findings were significant in a previous EWAS of maternal serum folate in cord blood. Results & conclusion: cg19888088 (cross-ancestry) in EBF3, cg01952260 (Europeans) and cg07077240 (South Asians) in HERC3 were associated with serum folate. cg19888088 and cg01952260 were associated with diastolic blood pressure. cg07077240 was associated with variants in CASC15. The findings were not replicated and were not significant in cord blood.
... Vitamin B12 is involved with immunomodulation, and therefore if patients have low vitamin B12 stores, this may in itself contribute to a hyperinflammatory or otherwise dysregulated response. Specifically, vitamin B12 has roles in immune regulatory pathways that when dysregulated can stimulate demyelination (Mikkelsen & Apostolopoulos, 2019). Additionally, vitamin B12 deficiency may decrease CD8 + cells and natural killer cell activity (Tamura et al., 1999) which has been associated with autoimmunity and inflammation as well as demyelinating diseases such as multiple sclerosis (Chanvillard et al, 2013;McBride & Striker, 2017;Pender, 2011). ...
Background: The COVID-19 vaccines have been an essential measure to help reduce COVID-19-related injury and death. However, in some cases, vaccination has caused severe and chronic reactions, akin to post-acute sequelae of COVID-19 (long COVID).
Cases: Here we present two cases (Case 1: male, age 43 years, Pfizer BNT162b2 vaccination; Case 2: female, age 30 years, Oxford-AstraZeneca ChAdOx1nCoV-19 vaccination) with severe neurological adverse reaction post-vaccine and concomitant vitamin B12 deficiency. Both cases presented with non-textbook symptomatology of vitamin B12 deficiency. Case 1 had full symptom resolution with vitamin B12 replacement therapy. In Case 2, frank vitamin D deficiency and chronically elevated D-dimer were also found. Case 2 is still undergoing replacement therapy and this manuscript will be updated as appropriate.
Discussion: Vaccines, including the COVID-19 vaccines, are known to cause severe and/or chronic neurological reactions in rare cases. We support screening for vitamin B12 deficiency prior to vaccination in high-risk groups (e.g. those following an animal produce free diet), those suffering atypical/chronic vaccine reactions, and those with similar conditions, such as post-acute sequelae of COVID-19 (long COVID). A hypothesis is also presented demonstrating the links between vitamin B12 and vitamin D deficiency and other pathologies (e.g. mast cell activation disorders) that, if validated, could help explain some vaccine hyperreactions.
... Folates play a critical role in both DNA and RNA synthesis in cells [1][2][3][4][5][6]. Insufficient dietary intake of folates or intestinal absorption, or defective folate transport disrupt purine and pyrimidine nucleotide synthesis, especially for rapidly proliferating tissues such as hematopoietic and immune systems [7][8][9]. Folate derivatives are anionic in physiological pH and require predominantly active transporters to pass through cell membranes [10][11][12][13][14]. Mammalians have three important membrane folate and folate derivative transporters, proton-coupled folate transporter (PCFT, encoded by SLC46A1), reduced folate carrier (RFC, encoded by SLC19A1) and folate receptors (FR) α, β, γ (encoded by FOLR1, 2 and 3) [10][11][12][13][14][15]. PCFT expression is restricted to the duodenum and jejunum, liver, thus enabling folates to be absorbed from the intestine [10][11][12][13][14]. Loss of function (LOF) mutations in the SLC46A1 gene have been reported to decrease folate reabsorption from the intestinal lumen leading to a condition called hereditary folate malabsorption (HFM) [13,16]. ...
Insufficient dietary folate intake, hereditary malabsorption, or defects in folate transport may lead to combined immunodeficiency (CID). Although loss of function mutations in the major intestinal folate transporter PCFT/SLC46A1 was shown to be associated with CID, the evidence for pathogenic variants of RFC/SLC19A1 resulting in immunodeficiency was lacking. We report two cousins carrying a homozygous pathogenic variant c.1042 G > A, resulting in p.G348R substitution who showed symptoms of immunodeficiency associated with defects of folate transport. SLC19A1 expression by peripheral blood mononuclear cells (PBMC) was quantified by real-time qPCR and immunostaining. T cell proliferation, methotrexate resistance, NK cell cytotoxicity, Treg cells and cytokine production by T cells were examined by flow cytometric assays. Patients were treated with and benefited from folinic acid. Studies revealed normal NK cell cytotoxicity, Treg cell counts, and naive-memory T cell percentages. Although SLC19A1 mRNA and protein expression were unaltered, remarkably, mitogen induced-T cell proliferation was significantly reduced at suboptimal folic acid and supraoptimal folinic acid concentrations. In addition, patients’ PBMCs were resistant to methotrexate-induced apoptosis supporting a functionally defective SLC19A1. This study presents the second pathogenic SLC19A1 variant in the literature, providing the first experimental evidence that functionally defective variants of SLC19A1 may present with symptoms of immunodeficiency.
... The data are taken from the USDA National Nutrient Database for Standard Reference (https://ndb.nal.usda.gov/ndb/) displays the most important micronutrient for vegans to be aware of (Guetterman et al. 2022;Mikkelsen and Apostolopoulos 2019;Stabler 2013;Yamada 2013). In addition, recent reports suggest that B12 might improve immunity against infections (dos Santos 2020; Shakoor et al. 2021). ...
... cg07077240 is located in the HERC3 gene, that negatively regulates the NF-Kb pathway which is an important activator of inflammatory and immune reactions [53]. Folate is a vital nutrient for regulation of the immune reaction and inflammatory response [54]. Therefore, methylation at these CpG sites could potentially play a role in inflammatory related processes associated with folate. ...
Aim
To perform an epigenome-wide association study (EWAS) of serum folate in maternal blood.
Methods
We performed cross-ancestry (Europeans=302, South Asians=161) and ancestry-specific EWAS in the EPIPREG cohort, followed by methyl quantitative trait loci (mQTL) analysis and association with cardiometabolic phenotypes. We attempted replication using folate intake estimated from a food frequency questionnaire and maternal blood methylation data from MoBa, and in a previous published EWAS of maternal serum folate in cord blood.
Results
cg19888088 (cross-ancestry) in EBF3 , cg01952260 (Europeans), and cg07077240 (South Asians) in HERC3 were associated with serum folate. cg19888088 and cg01952260 were associated with diastolic blood pressure. cg07077240 was associated with variants in CASC15 . The findings were not replicated in the independent samples.
Conclusion
Serum folate was associated with methylation at three CpG sites.
... The ferritin molecule can also act as a proinflammatory cytokine and has immunomodulating effects. Vitamin D has immunomodulatory effects and affects the epidermal barrier 11,16,19 . Therefore, low serum levels of these parameters might alter immune responses against Malassezia species that caused SD. ...
Background and Design: No evidence suggests that any micronutrients are associated with seborrheic dermatitis (SD). The etiopathogenesis of SD is attributed to excessive proliferation of Malassezia species in the skin, deterioration in epidermal barrier functions, and inflammation. Vitamin B12 affects the immune system. Moreover, the ferritin molecule can act as a proinflammatory cytokine and has immunomodulating effects. Vitamin D has immunomodulatory effects and affects the epidermal barrier. Therefore, we thought that low serum levels of these parameters might affect immune responses against Malassezia species that caused SD. The study aimed to compare the serum vitamin B12, ferritin, and vitamin D levels of patients with SD with healthy controls.
Materials and Methods: Patients aged 18-50 years who applied to the dermatology outpatient clinic and were found to have SD during dermatological examination were retrospectively reviewed. Serum vitamin B12, ferritin, and vitamin D levels of 63 patients with SD and 37 healthy controls were compared. Categorical variables were compared using chi-square analysis. Student's t-test was used to compare constant variables, and Pearson's correlation test was applied for the correlation analysis. P<0.05 was considered significant.
Results: No significant difference was found in the serum vitamin B12, ferritin, and vitamin D levels between the patient and control groups (p=0.227, p=0.381, p=0.611, respectively). In addition, no significant difference was found between the patient and control groups in terms of serum vitamin B12, ferritin, and vitamin D levels, which were categorized as deficient, insufficient, and adequate (p=0.31, p=0.53, and p=0.80, respectively).
Conclusion: Routine measurements of these values are not necessary, but since detected subclinical vitamin B12 deficiency was detected in the patient group, this should be investigated in prospective controlled studies with a large number of patients.
... Vitamin B 12 play a critical and vital role in the proper function of immune system chiefly as an immune-modulator [37]. Specifically, it has been observed that individuals who are deficient of Vitamin B 12 have low levels of CD8+ T cells and impaired activity of NK cells [38]. ...
Background
Calcium carbide (CaC 2 ) is a chemical primarily used in the production of acetylene gas. The misuse of CaC 2 to induce fruit ripening is a global challenge with a potential adverse effects to human health. Additionally, CaC 2 is known to contain some reasonable amount of arsenic and phosphorous compounds that are toxic and pose a danger to human health when ingested. The current study sought to characterize CaC 2 toxicity and elucidate any protective effects by cyanocobalamin (vitamin B 12 ), a well-established antioxidant and anti-inflammatory bio-molecule. Female Swiss white mice were randomly assigned into three groups; the first group was the control, while the second group was administered with CaC 2 . The third group received CaC 2 followed by administration of vitamin B12. The mice were sacrificed at 60 days post treatment, hematological, biochemical, glutathione assay, cytokine ELISA and standard histopathology was performed.
Results
CaC 2 administration did not significantly alter the mice body weight. CaC 2 administration resulted in a significant decrease in packed cell volume (PCV), hemoglobin (Hb), red blood cells (RBCs) and RBC indices; indicative of CaC 2 -driven normochromic microcytic anaemia. Further analysis showed CaC 2 -driven leukopenia. Evidently, vitamin B 12 blocked CaC 2 -driven suppression of PCV, Hb, RBCs and WBCs. Monocytes and neutrophils were significantly up-regulated by CaC 2 . CaC 2 -induced elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin signaled significant liver damage. Notably, vitamin B 12 stabilized AST, ALT and bilirubin in the presence of CaC 2, an indication of a protective effect. Histopathological analysis depicted that vitamin B 12 ameliorated CaC 2 -driven liver and kidney injury. CaC 2 resulted in the depletion of glutathione (GSH) levels in the liver; while in the brain, kidney and lungs, the GSH levels were elevated. CaC 2 administration resulted in elevation of pro-inflammatory cytokines TNF-α and IFN-γ. Vitamin B 12 assuaged the CaC 2 -induced elevation of these pro-inflammatory cytokines.
Conclusions
These findings demonstrate for the first time that oral supplementation with vitamin B 12 can protect mice against CaC 2 -mediated toxicity, inflammation and oxidative stress. The findings provide vital tools for forensic and diagnostic indicators for harmful CaC 2 exposure; while providing useful insights into how vitamin B 12 can be explored further as an adjunct therapy for CaC 2 toxicity.
... The study also showed that 66.5% off employees always eat breakfast, 55.3% of them are keen to drink milk and eat dairy products such as yogurt and cheese, these fermented milk contain probiotic bacteria that coexist in the intestine which is considered a factory for the production of many vitamins necessary for the body such as K, B1, B6, B12 and folic acid, it is a friendly bacteria and plays in improving the immunity of the digestive system against pathogenic microbes [35,36,37]. ...
The research included a spectroscopic study of the kinetic reactions for the colored produced complexes derived from two different electron-donating drugs (Salicylic acid and Paracetamol) with a diazotized reagent (2, 4-dinitroaniline) that accepts these electrons at different three pH functions (pH5, pH7 and pH9) and at a constant temperature (298°K). We studied the optimal conditions for each formed complex as well as the optimal ratios (stoichiometric ratios) of its components, which were (1:10) for (drug: reagent) respectively. Then, the kinetics of the formation for the above complexes was followed spectroscopically, and it was found that these interactions was proved that drug complex formation followed a Pseudo-first-order kinetic with respect to Salicylic acid or Paracetamol drug. We were able to calculate the rate constant(k1) for the formation of the two produced drug compounds. The highest value(k1) for the drug complex (SADDNA: Salicylic Acid Drug + Diazotized 2, 4-Dinitroaniline) is (0.0457min⁻¹ at pH7), and for the drug complex (PDDNA: Paracetamol Drug + Diazotized 2, 4-Dinitroaniline) is (0.0314 min⁻¹ at pH9). We also calculated the half-life-time(t1/2) for each of them, and it was (15.17min.) and (22.08min.), respectively, which is completely opposite to the values of their rate constants under the same conditions. The reaction of salicylic acid is faster than that of paracetamol, because salicylic acid has the formula C6H4(OH)COOH, where it is an OH group ortho to a carboxyl group. That is, the carboxyl group in it obtains its resonance with the phenol ring. This is why it reacts faster compared to the acetamide group found in paracetamol.
... The study also showed that 66.5% off employees always eat breakfast, 55.3% of them are keen to drink milk and eat dairy products such as yogurt and cheese, these fermented milk contain probiotic bacteria that coexist in the intestine which is considered a factory for the production of many vitamins necessary for the body such as K, B1, B6, B12 and folic acid, it is a friendly bacteria and plays in improving the immunity of the digestive system against pathogenic microbes [35,36,37]. ...
Propionibacterium acnes is a major colonizer and inhabitant of the human skin along with Staphylococcus. These genera considered as acne inducing bacteria, although often defined as a commensal. Biofilm formation by this two isolates lead to increase its pathogenicity and cause chronic infection. on the other hand, antibiotic resistance represents the main problem in the treatment the wide range of microorganisms as biofilm or planktonic state. All 40 samples were isolated from University of Baghdad- Iraq (College of Science-Biology deparment)- during the period September (2017) to January (2018) with an age range of (18-23) years were cultured on manitole agar to isolate Staphelococcus aureus. It was used ten types of antibiotics to test the sensitivity of this bacterium against them. All isolates of S. aureus were recorded as multidrug resistant and were considered as S. aureus. Only four samples gave positive results with this media. In this study Capsicum annuum and vancomycin tested against planktonic and biofilm states of S. epidermidis and Propionibacterium acnes. The activity of plant oil against planktonic cell was done by well diffusion method while the antibiofilm activity of plant oil and vancomycin was tested by Traditional Chinese Medicine (TCM). The results show that the plant oil and vancomycin have antibiofilm activity against premature and mature biofilm for S. epidermidis and Probionobacterium acnes. This acivity differ from one concentration to another by detection different percentages of inhibition. This study show choice to using plant oil is the best reducing biofilm that formed by microbial pathogens which is important to control the infections-biofilm.
... The study also showed that 66.5% off employees always eat breakfast, 55.3% of them are keen to drink milk and eat dairy products such as yogurt and cheese, these fermented milk contain probiotic bacteria that coexist in the intestine which is considered a factory for the production of many vitamins necessary for the body such as K, B1, B6, B12 and folic acid, it is a friendly bacteria and plays in improving the immunity of the digestive system against pathogenic microbes [35,36,37]. ...
Data security represents an immense consideration for all the institutions
(civil and military) that deal with data transition; cryptography represents
an essential tool to keep the data secure during its transmission through
the channels. This work proposed using the novel Sadiq-Emad-Eman SEE
integral transform as a tool in the cryptography field, where a distinctive
series is generated from the algebraic equation produced from applying
the transform to the numerical representation of the message letters. The
SEE integral transform is used as a symmetric cryptographic
cryptosystem to encrypt the transmitted plaintext. The Inverse SEE
integral transform is used to decrypt the received ciphertext back into its
original context
... The collected information included age, sex, weight, height and smoking habits. Additionally, the nutritional status of the participants was recorded based on a self-report of any known deficiencies in vitamins (vitamin D, vitamin B12 and folic acid) and iron (Fe), since such deficiencies may be linked to an inadequate immune response (19,20). Furthermore, the use of immunomodulatory substances (such as corticosteroids) and a medical history of any chronic disease were also recorded. ...
Soon after the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) pandemic in December, 2019, numerous research teams, assisted by vast capital investments, achieved vaccine development in a fraction of time. However, almost 8 months following the initiation of the European vaccination programme, the need for prospective monitoring of the vaccine‑induced immune response, its determinants and related side‑effects remains a priority. The present study aimed to quantify the immune response following full vaccination with the BNT162b2 coronavirus disease 2019 (COVID‑19) mRNA vaccine by measuring the levels of immunoglobulin G (IgG) titers in healthcare professionals. Moreover, common side‑effects and factors associated with IgG titers were identified. For this purpose, blood samples from 517 individuals were obtained and analysed. Blood sampling was performed at a mean period of 69.0±23.5 days following the second dose of the vaccine. SARS‑CoV‑2 IgG titers had an overall mean value of 4.23±2.76. Females had higher titers than males (4.44±2.70 and 3.89 ±2.84, respectively; P=0.007), while non‑smokers had higher titers than smokers (4.48±2.79 and 3.80±2.64, respectively; P=0.003). An older age was also associated with lower antibody titers (P<0.001). Moreover, the six most prevalent adverse effects were pain at the injection site (72.1%), generalized fatigue (40.5%), malaise (36.3%), myalgia (31,0%), headache (25.8%) and dizziness/weakness (21.6%). The present study demonstrated that the immune response after receiving the BNT162b2 COVID‑19 mRNA vaccine is dependent on various modifiable and non‑modifiable factors. Overall, the findings of the present study highlight two key aspects of the vaccination programs: First, the need for prospective immunosurveillance studies in order to estimate the duration of immunity, and second, the need to identify those individuals who are at a greater risk of developing low IgG titers in order to evaluate the need for a third dose of the vaccine.
To keep our body healthy and protected from infectious microbes, immunity is essential. The immune system (IS) predominantly comprised of innate and acquired immunity, and has evolved as a specific, complex, efficient, and regulated protective mechanism in human beings. The IS commands different macro and micronutrients to function properly. Dietary habits have an impact on immunity and inflammation. Investigations have shown that omega-3 fatty acids can mitigate inflammation whereas food items that may aggravate inflammation include processed meat, simple sugars, trans fats, and refined carbohydrates. The immunological function of gut antigens has been partially elucidated by germ-free models. But the large intestine, which has a high concentration of gut microbiota, does not contain much of the gut associated lymphoid tissue (GALT). The immune response, diet balance, and preserving the necessary levels of vitamins and minerals to fend off infections have been clearly discussed in this chapter. Further, an overview of food allergy and allergens are also included in this chapter.
The relationship between nutrition, inflammation, and cancer is complex. Healthy eating can boost the immune system and reduce cancer risk, but both inadequate and excessive nutrition can lead to inflammation and cancer. Vitamin B6 and B12 are crucial for overall health, and their deficiency can disrupt the immune system, leading to hyperhomocysteinemia, oxidative stress, and immune dysfunction. This deficiency can contribute to diseases like cardiovascular disease, kidney disease, neurovascular diseases, osteoporosis, and cancer. Adequate dietary intake of these vitamins can prevent inflammation, immune dysfunction, and cancer progression, with supplements addressing deficiencies. High doses of vitamin B6, exceeding daily recommendations, may protect against cancer by reducing inflammation, oxidative stress, advanced glycation end products (AGEs), hydrogen sulfide (H2S), sphingosine-1-phosphate (S1P), and preventing telomere shortening. Vitamin B6 also shows promise as an immunomodulatory agent in inflammatory conditions. Conversely, excessive vitamin B12 intake may promote tumorigenesis by enhancing one-carbon metabolism, increasing nucleic acid synthesis, and altering DNA methylation, all contributing to cancer. However, further research is needed to understand these mechanisms fully. In this chapter, we describe the intricate connections between, nutrition, inflammation, and cancer. Vitamin B6 and B12 are crucial for maintaining health. Adequate intake can prevent inflammation, immune dysfunction, and cancer, while excess vitamin B12 may have tumorigenic effects. Further research is essential to clarify these vitamins' roles in cancer and immune function.
The maintenance of numerous cellular processes is heavily reliant on vitamins, and their optimal availability in the body is crucial for maintaining good health. Vitamins have been a subject of sustained research interest due to their significant roles in disease prevention and their use as adjuncts in managing various conditions, such as cancers. Unlike fat-soluble vitamins, most water-soluble vitamins are easily excreted from the body, minimizing the risk of toxicity. This property makes them more suitable for larger doses. Among the water-soluble vitamins, the B vitamins hold particular importance. They are closely associated with DNA replication and repair pathways, playing a vital role in maintaining genetic integrity. Moreover, certain B vitamins are involved in energy metabolism pathways, contributing to the body’s overall vitality. Insufficient intake of various B vitamins can lead to an elevated risk of diverse adverse health effects and the development of diseases. These range from psychological disturbances to the progression of cancer. However, it’s important to note that excessive intake of certain B vitamins can also have detrimental effects on health. This chapter explores the multifaceted role of vitamin B in upholding health and mitigating the risk of diseases, including cancers.
Approximately five million children die each year from preventable causes, including respiratory infections, diarrhea, and malaria. Roughly half of those deaths are attributable to undernutrition, including micronutrient deficiencies (MNDs). The influence of infection on micronutrient status is well established: The inflammatory response to pathogens triggers anorexia, while pathogens and the immune response can both alter nutrient absorption and cause nutrient losses. We review the roles of vitamin A, vitamin D, iron, zinc, and selenium in the immune system, which act in the regulation of molecular- or cellular-level host defenses, directly affecting pathogens or protecting against oxidative stress or inflammation. We further summarize high-quality evidence regarding the synergistic or antagonistic interactions between MNDs, pathogens, and morbidity or mortality relevant to child health in low- and middle-income countries. We conclude with a discussion of gaps in the literature and future directions for multidisciplinary research on the interactions of MNDs, infection, and inflammation.
In this overview, the latest achievements in dietary origins, absorption mechanism, bioavailability assay, health advantages, cutting-edge encapsulation techniques, fortification approaches, and innovative highly sensitive sensor-based detection methods of vitamin B12 (VB12) were addressed. The cobalt-centered vitamin B is mainly found in animal products, posing challenges for strict vegetarians and vegans. Its bioavailability is highly influenced by intrinsic factor, absorption in the ileum, and liver reabsorption. VB12 mainly contributes to blood cell synthesis, cognitive function, and cardiovascular health, and potentially reduces anemia and optic neuropathy. Microencapsulation techniques improve the stability and controlled release of VB12. Co-microencapsulation of VB12 with other vitamins and bioactive compounds enhances bioavailability and controlled release, providing versatile initiatives for improving bio-functionality. Nanotechnology, including nanovesicles, nanoemulsions, and nanoparticles can enhance the delivery, stability, and bioavailability of VB12 in diverse applications, ranging from antimicrobial agents to skincare and oral insulin delivery. Staple food fortification with encapsulated and free VB12 emerges as a prominent strategy to combat deficiency and promote nutritional value. Biosensing technologies, such as electrochemical and optical biosensors, offer rapid, portable, and sensitive VB12 assessment. Carbon dot-based fluorescent nanosensors, nanocluster-based fluorescent probes, and electrochemical sensors show promise for precise detection, especially in pharmaceutical and biomedical applications.
COVID-19 is highly linked with hyperinflammation and dysfunction of the immune cells. Studies have shown that adequate nutrition, a modifiable factor affecting immunity and limiting systemic inflammation, may play an adjunct role in combating the negative consequences of SARS-CoV-2 infection. Due to the global lockdown conditions, the COVID-19 pandemic has contributed, among others, to restrictions on fresh food availability and changes in lifestyle and eating behaviors. The aim of this paper was to review the data regarding eating habits in European countries within the general population of adults and some specific subpopulations, including obese, diabetic, and psychiatric patients, during the COVID-19 pandemic. The PubMed database and the official websites of medical organizations and associations were searched for the phrases “COVID” and “eating habits”. Papers regarding the pediatric population, non-European countries, presenting aggregated data from different countries worldwide, and reviews were excluded. During the COVID-19 pandemic, unhealthy lifestyles and eating behaviors were commonly reported. These included increased snacking, intake of caloric foods, such as sweets, pastries, and beverages, and a decline in physical activity. Data suggest that poor eating habits that create a positive energy balance have persisted over time as an additional post-COVID negative consequence.
Micronutrient deficiency is a form of malnutrition responsible for different metabolic diseases, widely shared among developing low-and middle-income African countries. While deficiencies of calcium, iron, vitamin A, zinc, and selenium have been counteracted mainly by implementing mandatory food fortification programs, little attention was given so far on strategies to decrease inadequate intake of water-soluble B-group vitamins. In this review, we summarize the physiological role of B-group vitamins, and discuss the approaches commonly used to tackle their deficiencies in Africa, namely (i) dietary diversification, (ii) supplementation, and (iii) fortification, with the main focus being here the microbial-based biofortification of food. We report the increasing evidence of plant-based African fermented foods as important sources of these vitamins and how microbial-based biofortification strategies may enhance their content and bioavailability during plant-based fermentation, especially seen for folate (vitamin B9), riboflavin (vitamin B2), and cobalamin (vitamin B12). The selection of pro-technological functional microbial strains from spontaneous fermentation and/or unconventional food matrices, the employment of vitamin overproducing lactic acid bacteria, as well as the implementation of adequate food processes are promising tools that could be implemented in the production of staple home-made fermented foods to counteract B-group vitamins deficiencies. Further research is needed to explore the biotechnological potential of underexploited indigenous microbial strains and the impact of fortified foods on gut host health
Vitamin B12 and folate deficiencies can be frequently seen in children and adolescents and may manifest with neuropsychiatric symptoms. Vitamin B12 and folate deficiencies and the associated increase in homocysteine are related to one-carbon metabolism (OCM) and may play a role in the pathogenesis of childhood and adolescent psychiatric disorders. Here, twelve adolescent cases with vitamin B12 and folate deficiencies and homocysteine increase, diagnosed with major depressive disorder, generalized anxiety disorder and obsessive compulsive disorder are presented. The possible biochemical roles of OCM in the pathogenesis of psychiatric disorders at these ages were explained. In addition, the diagnosis and treatment methods for vitamin B12 and folate deficiencies are summarized for clinicians.
Infection with Trypanosoma brucei rhodesiense (T.b.r) causes acute Human African Trypanosomiasis (HAT) in Africa. This study determined the effect of vitamin B12 on T.b.r -driven pathological events in a mouse model. Mice were randomly assigned into four groups; group one was the control. Group two was infected with T.b.r; group three was supplemented with 8 mg/kg vitamin B12 for two weeks; before infection with T.b.r. For group four, administration of vitamin B12 was started from the 4th days post-infection with T.b.r. At 40 days post-infection, the mice were sacrificed to obtain blood, tissues, and organs for various analyses. The results showed that vitamin B12 administration enhanced the survival rate of T.b.r infected mice, and prevented T.b.r-induced disruption of the blood-brain barrier and decline in neurological performance. Notably, T.b.r-induced hematological alteration leading to anaemia, leukocytosis and dyslipidemia was alleviated by vitamin B12. T.b.r-induced elevation of the liver alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin as well as the kidney damage markers urea, uric acid and creatinine were attenuated by vitamin B12. Vitamin B12 blocked T.b.r-driven rise in TNF-α and IFN-γ, nitric oxide and malondialdehyde. T.b.r-induced depletion of GSH levels were attenuated in the presence of vitamin B12 in the brain, spleen and liver tissues; a clear indication of the antioxidant activity of vitamin B12. In conclusion, treatment with vitamin B12 potentially protects against various pathological events associated with severe late-stage HAT and presents a great opportunity for further scrutiny to develop an adjunct therapy for severe late-stage HAT.
With over 6 million coronavirus pandemic deaths, the African continent reported the lowest death rate despite having a high disease burden. The African community’s resilience to the pandemic has been attributed to climate and weather conditions, herd immunity, repeated exposure to infectious organisms that help stimulate the immune system, and a disproportionately large youth population. In addition, functional foods, herbal remedies, and dietary supplements contain micronutrients and bioactive compounds that can help boost the immune system. This review identified significant traditional fermented foods and herbal remedies available within the African continent with the potential to boost the immune system in epidemics and pandemics. Methodology: Databases, such as PubMed, the Web of Science, and Scopus, were searched using relevant search terms to identify traditional African fermented foods and medicinal plants with immune-boosting or antiviral capabilities. Cereal-based fermented foods, meat-, and fish-based fermented foods, and dairy-based fermented foods containing antioxidants, immunomodulatory effects, probiotics, vitamins, and peptides were identified and discussed. In addition, nine herbal remedies and spices belonging to eight plant families have antioxidant, immunomodulatory, anti-inflammatory, neuroprotective, hepatoprotective, cardioprotective, and antiviral properties. Peptides, flavonoids, alkaloids, sterols, ascorbic acid, minerals, vitamins, and saponins are some of the bioactive compounds in the remedies. Bioactive compounds in food and plants significantly support the immune system and help increase resistance against infectious diseases. The variety of food and medicinal plants found on the African continent could play an essential role in providing community resilience against infectious diseases during epidemics and pandemics. The African continent should investigate nutritional, herbal, and environmental factors that support healthy living and longevity.
Insufficient dietary folate intake, hereditary malabsorption, or defects in folate metabolism may lead to combined immunodeficiency (CID). Although loss of function mutations in the major intestinal folate transporter PCFT/SLC46A1 was shown to be associated with CID, the evidence for pathogenic variants of RFC/SLC19A1 resulting in immunodeficiency was lacking. We report two cousins carrying a homozygous pathogenic variant c.1042G>A, resulting in p.G348R substitution who showed symptoms of immunodeficiency associated with defects of folate metabolism. SLC19A1 expression by peripheral blood mononuclear cells (PBMC) was quantified by real-time qPCR and immunostaining. T cell proliferation, methotrexate resistance, NK cell cytotoxicity, Treg cells and cytokine production by T cells were examined by flow cytometric assays. Patients were treated with and benefited from folinic acid (FA). Studies revealed normal NK cell cytotoxicity, Treg cell counts, and naive-memory T cell percentages. Although SLC19A1 mRNA and protein expression were unaltered, remarkably, mitogen induced-T cell proliferation was significantly reduced at sub- and supraoptimal folic acid concentrations. In addition, patients’ PBMCs were resistant to methotrexate-induced apoptosis supporting a functionally defective SLC19A1.
This study presents the second pathogenic SLC19A1 variant in the literature, providing the first experimental evidence that loss of function mutations in SLC19A1 may present with symptoms of immunodeficiency.
Shellfish, in particular bivalves, are an often-overlooked source of vitamin B12 (B12) in the human diet although they have significantly higher tissue levels of B12 than other animal meat or fish sources, including all vertebrates. However, the origins and key metabolic processes involving B12 in bivalves remain largely unknown. In this study, we examined the distribution of B12 in tissues of several adult Australian bivalve species and assessed hypotheses concerning their B12 utilisation and principal uptake, specifically whether it is derived from diet or gut microbiome. Pacific oysters, Crassostrea gigas, and Goolwa cockles, Plebidonax deltoides (‘pipis’), are both high in B12 (28.0–49.4 μg/100 g total per individual). Vitamin B12 tissue distribution, particularly in oysters, varied significantly, with higher amounts in the adductor muscle (44.0–96.7 μg/100 g), and other tissues, such as gonads, were relatively low (12.7–35.9 μg/100 g). In comparison, concentrations of B12 in the adductor muscle and roe of Southern Australian scallops, Pecten fumatus, were appreciably lower (3.4–10.8 μg/100 g). We also demonstrated that microalgal feed commonly grown in aquaculture can be supplemented directly with B12, resulting in an enriched feed. However, the B12-enriched diet did not transfer to a significant increase in oyster larval B12 concentrations, contradicting our theory that vitamin uptake through feed was a primary B12 source. Vitamin B12 concentrations across oyster larval life stages showed a significant decrease post metamorphosis, which indicates a higher utilisation of B12 during this life event. Our findings also provide insight into B12 uptake and tissue distribution in bivalve species, which can aid the aquaculture industry in promotion of bivalves as a valuable source of dietary B12 for human consumers, while also suggesting ways to optimise vitamin supplementation in bivalve hatchery production.
Insufficient dietary folate intake, hereditary malabsorption, or defects in folate metabolism may lead to combined immunodeficiency (CID). Although loss of function mutations in the major intestinal folate transporter PCFT/SLC46A1 was shown to be associated with CID, the evidence for pathogenic variants of RFC/SLC19A1 resulting in immunodeficiency was lacking. In this study, we report two cousins carrying a homozygous pathogenic variant c.1042G>A, resulting in p.G348R substitution who showed clinical symptoms of immunodeficiency associated with defects of folate metabolism. The mutation was identified by whole-exome sequencing. SLC19A1 expression by peripheral blood mononuclear cells (PBMC) was quantified by real-time qPCR and immunostaining. T cell proliferation, methotrexate resistance, NK cell cytotoxicity, Treg cells and cytokine production by T cells were examined by flow cytometric assays. Both patients were treated with and clinically benefited from folinic acid (FA). Functional studies revealed normal NK cell cytotoxicity, Treg cell counts, and naive-memory T cell percentages. Although SLC19A1 mRNA and protein expression were unaltered, remarkably, mitogen induced-T cell proliferation was significantly reduced at sub- and supraoptimal folic acid concentrations. In addition, both patients’ PBMCs were resistant to methotrexate-induced apoptosis supporting a functionally defective SLC19A1 variant.
This study, to our knowledge, presents the second pathogenic SLC19A1 variant in the literature, providing the first experimental evidence that loss of function mutations in SLC19A1 may present with symptoms of immunodeficiency, and that those defects could benefit from FA supplementation.
AIM: This study aims to evaluate the nutritional content and physicochemical aspect of the combination of eel and tempe flour. METHODS: Samples of swamp eel and tempe flour were combined in a ratio of 1:1 (A), 1:2 (B), 1:3.5 (C), and 1 kilogram of Asian swamp eel meat without additional tempe (D), respectively. Homogenization was done using a sinmag planetary mixer. The sample analysis was performed at the SIG Laboratory (PT. Saraswanti Indo Genetech) on November 16, 2021. The samples were analyzed triple (triplicates). Statistical analysis was performed using GraphPad Prism version 9.3.0 for Mac OS. Variables were analyzed using multivariate ANOVA with 95% CI (0.05). RESULTS: There was a significant difference between Samples A, B, C, and D for every proximate analysis parameter (p = 0.000) p < 0.05. The results showed a significant difference in the unsaturated fatty acid parameter between the groups (p < 0.001). Sample C has the highest B9 (folic acid) content compared to other samples (1258.53 ± 1.39 mcg/100 g) and a significant difference was found between samples (p < 0.0001). CONCLUSION: Tempe flour enriched eel flour can act as a source of folate, due to its high folate content. Tempe flour enriched eel flour could be used as a flour mixture in any food products that require flour to increase folate content.
An association between arteriosclerosis and homocysteine (Hcy) was first demonstrated in 1969. Hcy is a sulfur containing amino acid derived from the essential amino acid methionine (Met). Hyperhomocysteinemia (HHcy) was subsequently shown in several age-related pathologies such as osteoporosis, Alzheimer’s disease, Parkinson’s disease, stroke, and cardiovascular disease (CVD). Also, Hcy is associated with (but not limited to) cancer, aortic aneurysm, hypothyroidism and end renal stage disease to mention some. The circulating levels of Hcy can be increased by defects in enzymes of the metabolism of Met, deficiencies of vitamins B6, B12 and folate or by feeding Met enriched diets. Additionally, some of the pharmaceuticals currently in clinical practice such as lipid lowering, and anti-Parkinsonian drugs are known to elevate Hcy levels. Studies on supplementation with folate, vitamins B6 and B12 have shown reduction in Hcy levels but concomitant reduction in certain associated pathologies have not been definitive. The enormous importance of Hcy in health and disease is illustrated by its prevalence in the medical literature (e.g. > 22,000 publications). Although there are compelling data in favor of Hcy as a modifiable risk factor, the debate regarding the significance of Hcy mediated health effects is still ongoing. Despite associations between increased levels of Hcy with several pathologies being well documented, whether it is a causative factor, or an effect remains inconclusive. The present review though not exhaustive, is focused on several important aspects of Hcy metabolism and their relevance to health.
High plasma levels of homocysteine, termed hyperhomocysteinemia, are a risk factor for vascular cognitive impairment and dementia, which is the second leading cause of dementia. While hyperhomocysteinemia induces microhemorrhages and cognitive decline in mice, the specific effect of hyperhomocysteinemia on each cell type remains unknown. We took separate cultures of astrocytes, microglia, endothelial cells, and neuronal cells and treated each with moderate levels of homocysteine for 24, 48, 72, and 96 hr. We then determined the gene expression changes for cell-specific markers and neuroinflammatory markers including the matrix metalloproteinase 9 system. Astrocytes had decreased levels of several astrocytic end feet genes, such as aquaporin 4 and an adenosine triphosphate (ATP)-sensitive inward rectifier potassium channel at 72 hr, as well as an increase in matrix metalloproteinase 9 at 48 hr. Gene changes in microglia indicated a peak in proinflammatory markers at 48 hr followed by a peak in the anti-inflammatory marker, interleukin 1 receptor antagonist, at 72 hr. Endothelial cells had reduced occludin expression at 72 hr, while kinases and phosphatases known to alter tau phosphorylation states were increased in neuronal cells. This suggests that hyperhomocysteinemia induces early proinflammatory changes in microglia and astrocytic changes relevant to their interaction with the vasculature. Overall, the data show how hyperhomocysteinemia could impact Alzheimer’s disease and vascular cognitive impairment and dementia.
The folate pathway is critical to proper cellular function and metabolism. It is responsible for multiple functions, including energy (ATP) production, methylation reactions for DNA and protein synthesis and the production of immunomodulatory molecules, inosine and adenosine. These play an important role in immune signaling and cytotoxicity. Herein, we hypothesize that defects in the folate pathway in genetically susceptible individuals could lead to immune dysfunction, permissive environments for chronic cyclical latent/lytic viral infection, and, ultimately, the development of unchecked autoimmune responses to infected tissue, in this case islet beta cells. In the context of type 1 diabetes (T1D), there has been a recent increase in newly diagnosed cases of T1D in the past 20 years that has exceeded previous epidemiological predictions with yet unidentified factor(s). This speaks to a potential environmental trigger that adversely affects immune responses. Most research into the immune dysfunction of T1D has focused on downstream adaptive responses of T and B cells neglecting the role of the upstream innate players such as natural killer (NK) cells. Constantly, surveilling the blood and tissues for pathogens, NK cells remove threats through direct cytotoxic responses and recruitment of adaptive responses using cytokines, such as IL-1β and IFN-γ. One long-standing hypothesis suggests viral infection as a potential trigger for the autoimmune response in T1D. Recent data suggest multiple viruses as potential causal agents. Intertwined with this is an observed reduced NK cell enumeration, cytotoxicity, and cytokine signaling in T1D patients. Many of the viruses implicated in T1D are chronic latent/lysogenic infections with demonstrated capacity to reduce NK cell response and number through mechanisms that resemble those of pregnancy tolerance. Defects in the folate pathway in T1D patients could result in decreased immune response to viral infection or viral reactivation. Dampened NK responses to infections result in improper signaling, improper antigen presentation, and amplified CD8⁺ lymphocyte proliferation and cytotoxicity, a hallmark of beta cell infiltrates in patients with T1D onset. This would suggest a critical role for NK cells in T1D development linked to viral infection and the importance of the folate pathway in maintaining proper NK response.
The purpose of this study was to investigate whether plasma pyridoxal 5'-phosphate (PLP) and homocysteine were dependent on or independent of each other in order to be associated with inflammatory markers in patients with chronic kidney disease (CKD) or those receiving hemodialysis treatment. This was a cross-sectional study. Sixty-eight stage 2-5 CKD patients and 68 hemodialysis patients had one time fasting blood drawn for measurements of plasma PLP, pyridoxal (PL), homocysteine, and several inflammatory markers. Early CKD stage (stages 2-3) patients showed significantly lower plasma PLP levels and homocysteine concentrations than patients in an advanced CKD stage (stages 4-5) and those undergoing hemodialysis. Plasma PLP significantly correlated with CRP levels (partial r
s
= -0.21, p < 0.05) and plasma PL significantly correlated with IL-10 levels (partial r
s
= -0.24, p < 0.01), while plasma PLP plus PL significantly correlated with both CRP levels (partial r
s
= -0.20, p < 0.05) and interleukin-1β (partial r
s
= 0.22, p < 0.05) levels after adjusting for plasma homocysteine and other potential confounders. Plasma homocysteine displayed no significant correlations with any inflammatory markers. Vitamin B-6 status, rather than homocysteine, appeared to be a significant factor in relation to inflammatory responses for CKD and hemodialysis patients.
While dietary folate deficiency is associated with increased risk for birth defects and other diseases, evidence suggests that supplementation with folic acid can contribute to predisposition to some diseases, including immune dysfunction and cancer. Here we show that diets supplemented with folic acid both below and above the recommended levels led to significantly altered metabolism in multiple tissues in mice. Surprisingly, both low and excessive dietary folate induced similar metabolic changes, which were particularly evident for nucleotide biosynthetic pathways in B-progenitor cells. Diet-induced metabolic changes in these cells partially phenocopied those observed in mice treated with anti-folate drug, suggesting that both deficiency and excessive levels of dietary folic acid compromise folate-dependent biosynthetic pathways. Both folate deficiency and excessive dietary folate levels compromise hematopoiesis resulting in defective cell cycle progression, persistent DNA damage, and impaired production of lymphocytes. These defects reduce reconstitution potential in transplantation settings and increase radiation-induced mortality. We conclude that excessive folic acid supplementation can metabolically mimic dietary folate insufficiency, leading to similar functional impairment of hematopoiesis.
Background: The effects of high-dose folic acid (FA) supplementation in healthy individuals on blood folate concentrations and immune response are unknown.
Objective: The aim of the study was to evaluate the effects of daily consumption of a tablet containing 5 mg FA on serum folate; number and cytotoxicity of natural killer (NK) cells; mRNA expression of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), interferon γ (IFNG), tumor necrosis factor α (TNFA), and interleukin 8 (IL8) genes; and concentrations of serum inflammatory markers.
Methods: This prospective clinical trial was conducted in 30 healthy Brazilian adults (15 women), aged 27.7 y (95% CI: 26.4, 29.1 y), with a body mass index (in kg/m2) of 23.1 (95% CI: 22.0, 24.3). Blood was collected at baseline and after 45 and 90 d of the intervention. Serum folate concentrations were measured by microbiological assay and HPLC–tandem mass spectrometry [folate forms, including unmetabolized folic acid (UMFA)]. We used real-time polymerase chain reaction to assess mononuclear leukocyte mRNA expression and flow cytometry to measure the number and cytotoxicity of NK cells.
Results: Serum folate concentrations increased by ∼5-fold after the intervention (P < 0.001), and UMFA concentrations increased by 11.9- and 5.9-fold at 45 and 90 d, respectively, when compared with baseline (P < 0.001). UMFA concentrations increased (>1.12 nmol/L) in 29 (96.6%) participants at day 45 and in 26 (86.7%) participants at day 90. We observed significant reductions in the number (P < 0.001) and cytotoxicity (P = 0.003) of NK cells after 45 and 90 d. Compared with baseline, DHFR mRNA expression was higher at 90 d (P = 0.006) and IL8 and TNFA mRNA expressions were higher at 45 and 90 d (P = 0.001 for both).
Conclusion: This noncontrolled intervention showed that healthy adults responded to a high-dose FA supplement with increased UMFA concentrations, changes in cytokine mRNA expression, and reduced number and cytotoxicity of NK cells. This trial was registered at www.ensaiosclinicos.gov.br as RBR-2pr7zp.
Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways. The deficiency of vitamin B12 is clinically manifested in the blood and nervous system where the cobalamin plays a key role in cell replication and in fatty acid metabolism. Hypovitaminosis arises from inadequate absorption, from genetic defects that alter transport through the body, or from inadequate intake as a result of diet. With the growing adoption of vegetarian eating styles in Western countries, there is growing focus on whether diets that exclude animal foods are adequate. Since food availability in these countries is not a problem, and therefore plant foods are sufficiently adequate, the most delicate issue remains the contribution of cobalamin, which is poorly represented in plants. In this review, we will discuss the status of vitamin B12 among vegetarians, the diagnostic markers for the detection of cobalamin deficiency and appropriate sources for sufficient intake, through the description of the features and functions of vitamin B12 and its absorption mechanism.
Rationale:
Patients with chronic kidney disease (CKD) develop hyperhomocysteinemia and have a higher cardiovascular mortality than those without hyperhomocysteinemia by 10-fold.
Objective:
We investigated monocyte differentiation in human CKD and cardiovascular disease (CVD).
Methods and results:
We identified CD40 as a CKD-related monocyte activation gene using CKD-monocyte -mRNA array analysis and classified CD40 monocyte (CD40(+)CD14(+)) as a stronger inflammatory subset than the intermediate monocyte (CD14(++)CD16(+)) subset. We recruited 27 patients with CVD/CKD and 14 healthy subjects and found that CD40/CD40 classical/CD40 intermediate monocyte (CD40(+)CD14(+)/CD40(+)CD14(++)CD16(-)/CD40(+)CD14(++)CD16(+)), plasma homocysteine, S-adenosylhomocysteine, and S-adenosylmethionine levels were higher in CVD and further elevated in CVD+CKD. CD40 and CD40 intermediate subsets were positively correlated with plasma/cellular homocysteine levels, S-adenosylhomocysteine and S-adenosylmethionine but negatively correlated with estimated glomerular filtration rate. Hyperhomocysteinemia was established as a likely mediator for CKD-induced CD40 intermediate monocyte, and reduced S-adenosylhomocysteine/S-adenosylmethionine was established for CKD-induced CD40/CD40 intermediate monocyte. Soluble CD40 ligand, tumor necrosis factor (TNF)-α/interleukin (IL)-6/interferon (IFN)-γ levels were elevated in CVD/CKD. CKD serum/homocysteine/CD40L/increased TNF-α/IL-6/IFN-γ-induced CD40/CD40 intermediate monocyte in peripheral blood monocyte. Homocysteine and CKD serum-induced CD40 monocyte were prevented by neutralizing antibodies against CD40L/TNF-α/IL-6. DNA hypomethylation was found on nuclear factor-κB consensus element in CD40 promoter in white blood cells from patients with CKD with lower S-adenosylmethionine / S-adenosylhomocysteine ratios. Finally, homocysteine inhibited DNA methyltransferase-1 activity and promoted CD40 intermediate monocyte differentiation, which was reversed by folic acid in peripheral blood monocyte.
Conclusions:
CD40 monocyte is a novel inflammatory monocyte subset that appears to be a biomarker for CKD severity. Hyperhomocysteinemia mediates CD40 monocyte differentiation via soluble CD40 ligand induction and CD40 DNA hypomethylation in CKD.
Vitamins are dietary components which are necessary for life. They play a major role in health and their deficiency may be linked to symptoms of psychiatric disorders. B vitamins are required for proper functioning of the methylation cycle, monoamine oxidase production, DNA synthesis and the repair and maintenance of phospholipids. Vitamin B deficiency could influence memory function, cognitive impairment and dementia. In particular, vitamins B1, B3, B6, B9 and B12 are essential for neuronal function and deficiencies have been linked to depression. We discuss the causes of depression and the neurochemical pathways in depression. In particular, we provide evidence that vitamin B contributes to the complexity of depressive symptoms.
Background:
This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population.
Methods:
A total of 364 subjects (224 children, age: 12.99 ± 2.73 (mean ± SD) years; BMI: 20.07 ± 4.92 kg/m² and 140 adults, age: 41.87 ± 8.82 years; BMI: 31.65 ± 5.77 kg/m²) were studied. Fasting blood, anthropometric and biochemical data were collected. Serum cytokines were quantified using multiplex assay kits and B12 concentrations were measured using immunoassay analyzer.
Results:
Vitamin B12 was negatively associated with TNF-α (r = -0.14, p < 0.05), insulin (r = -0.230, p < 0.01) and HOMA-IR (r = -0.252, p < 0.01) in all subjects. In children, vitamin B12 was negatively associated with serum resistin (r = -0.160, p < 0.01), insulin (r = -0.248, p < 0.01), HOMA-IR (r = -0.261, p < 0.01). In adults, vitamin B12 was negatively associated with TNF-α (r = -0.242, p < 0.01) while positively associated with resistin (r = 0.248, p < 0.01). Serum resistin was the most significant predictor for circulating vitamin B12 in all subjects (r² = -0.17, p < 0.05) and in children (r² = -0.167, p < 0.01) while HDL-cholesterol was the predictor of B12 in adults (r² = -0.78, p < 0.05).
Conclusions:
Serum vitamin B12 concentrations were associated with pro-inflammatory cytokines and biochemical markers of cardiometabolic risks in adults. Maintaining adequate vitamin B12 concentrations may lower inflammation-induced cardiometabolic risk in the Saudi adult population.
Background:
Results from observational and genetic epidemiological studies suggest that lower serum homocysteine levels are associated with lower incidence of cardiovascular disease (CVD). Numerous randomized controlled trials have investigated the efficacy of lowering homocysteine with folic acid supplementation for CVD risk, but conflicting results have been reported.
Methods and results:
Three bibliographic databases (Medline, Embase, and the Cochrane Database of Systematic Reviews) were searched from database inception until December 1, 2015. Of the 1933 references reviewed for eligibility, 30 randomized controlled trials involving 82 334 participants were included in the final analysis. The pooled relative risks of folic acid supplementation compared with controls were 0.90 (95% CI 0.84-0.96; P=0.002) for stroke, 1.04 (95% CI 0.99-1.09; P=0.16) for coronary heart disease, and 0.96 (95% CI 0.92-0.99; P=0.02) for overall CVD. The intervention effects for both stroke and combined CVD were more pronounced among participants with lower plasma folate levels at baseline (both P<0.02 for interaction). In stratified analyses, a greater beneficial effect for overall CVD was seen in trials among participants without preexisting CVD (P=0.006 for interaction) or in trials with larger reduction in homocysteine levels (P=0.009 for interaction).
Conclusions:
Our meta-analysis indicated a 10% lower risk of stroke and a 4% lower risk of overall CVD with folic acid supplementation. A greater benefit for CVD was observed among participants with lower plasma folate levels and without preexisting CVD and in studies with larger decreases in homocysteine levels. Folic acid supplementation had no significant effect on risk of coronary heart disease.
Background: Micronutrients such as B12 and folic acid deficiencies are found in higher number in HIV-infected patients.
Objective: We conducted a study to examine the effect of Vitamin B12 and folic acid supplementation on neuropsychiatric manifestations, CD4 count, and anthropometric measurements in HIV-positive patients.
Materials and Methods: Three different groups of HIV patients, namely, HIV patients with tuberculosis, HIV patients with neuropsychiatric manifestations, and asymptomatic HIV patients with 50 patients in each group were included in the study. Baseline and follow-up CD4 count, anthropometric measurements, neuropsychiatric assessments, Vitamin B12, and folic acid estimation were done.
Results: The prevalence of folic acid deficiency was 27.1% in Group I, 31.9% in Group II, and 23.4% in Group III. The prevalence of Vitamin B12 deficiency was 8.16% in Group I, 6.12% in Group II, and 4.16% in Group III. HIV patients with neuropsychiatric manifestations were noted to have the lowest mean mini–mental score. After the supplementation of vitamins, anthropometric measurements, MMSE as well as Hamilton depression scores, improved in all the three groups whereas Hamilton anxiety scores improved only in Group III. The CD4 count also improved in Groups I and II after the supplementation of vitamins.
Conclusion: Folic acid deficiency was highest among neuropsychiatric patients. The majority of people who had a folic acid deficiency have shown improvement in their neuropsychiatric assessment scores as well as CD4 count after its supplementation.
Malaria is a significant global health issue, with nearly 200 million cases in 2013 alone. Parasites obtain folate from the host or synthesize it de novo. Folate consumption has increased in many populations, prompting concerns regarding potential deleterious consequences of higher intake. The impact of high dietary folate on the host's immune function and response to malaria has not been examined. Our goal was to determine whether high dietary folate would affect response to malarial infection in a murine model of cerebral malaria. Mice were fed control diets (CD, recommended folate level for rodents) or folic acid-supplemented diets (FASD, 10x recommended level) for 5 weeks before infection with Plasmodium berghei ANKA. Survival, parasitemia, numbers of immune cells and other infection parameters were assessed. FASD mice had reduced survival (p<0.01, Cox proportional hazards) and higher parasitemia (p< 0.01, joint model of parasitemia and survival) compared with CD mice. FASD mice had lower numbers of splenocytes, total T cells, and lower numbers of specific T and NK cell sub-populations, compared with CD mice (p<0.05, linear mixed effects). Increased brain TNFα immunoreactive protein (p<0.01, t-test) and increased liver Abca1 mRNA (p<0.01, t-test), a modulator of TNFα, were observed in FASD mice; these variables correlated positively (rs = 0.63, p = 0.01). Bcl-xl/Bak mRNA was increased in liver of FASD mice (p<0.01, t-test), suggesting reduced apoptotic potential. We conclude that high dietary folate increases parasite replication, disturbs the immune response and reduces resistance to malaria in mice. These findings have relevance for malaria-endemic regions, when considering anti-folate anti-malarials, food fortification or vitamin supplementation programs.
Objectives: Vitamin B-12 and n-3 polyunsaturated fatty acids (PUFA) decrease blood homocysteine (Hcy) concentrations. However, the combined effect of these nutrients on Hcy and ferritin, and C-reactive protein is limited and inconclusive. The objective was to examine the synergistic effect of vitamin B-12 in combination of n-3 PUFA on plasma Hcy, ferritin, and other biochemical markers. Methods: In a randomized controlled trial, thirty eligible subjects were randomly divided into three groups, and assigned to receive 1000 μg of vitamin B-12, 2 g fish oil, or 1000 μg vitamin B-12 and 2 g fish oil, respectively, for 8 weeks. Plasma phospholipids (PL) fatty acids and biochemical markers were determined. This study was registered under ClinicalTrials.gov Identifier: NCT01762072. Results: Plasma PL 20:5n-3, 22:6n-3 and n-3 PUFA was increased after 4 and 8 week supple-mentation of fish oil, and vitamin B-12+fish oil. Plasma concentrations of triacylglycerol, uric acid, C-reactive protein, and ferritin were significantly decreased after 4 and 8 week supplementation of fish oil, and vitamin B-12+fish oil. In all groups, significant changes in plasma Hcy were observed during the study period. Vitamin B-12, fish oil, and vitamin B-12+fish oil supplementation lowered plasma Hcy concentrations by 22%, 19%, and 39%, respectively. Conclusions: The combination of vitamin B-12 and fish oil has a synergistic effect on lowering plasma concentrations of Hcy.
Patients with chronic kidney disease (CKD) have high incidence rates
of cardiovascular disease and malignancy. Several factors contribute
to these conditions. Structural characteristics in CKD, loss of renal
energy, and uremia result in an imbalance between free radical
production and antioxidant defenses. Also, CKD patients usually
have multiple cardiovascular risk factors like diabetes mellitus,
dyslipidemia, and hypertension. These conditions are associated
with oxidative stress, which can trigger the inflammatory process
and accelerate renal injury progression. There are some clinical
biomarkers to detect oxidative stress and antioxidant status in
CKD patients. Antioxidant therapies may be beneficial in reducing
oxidative stress, lowering uremic cardiovascular toxicity, and
improving survival. Therefore, their roles in CKD patients have
been evaluated in several studies as a new target for therapeutic
intervention. This review provides an overview of oxidative stress
mechanisms, clinical squeals, biomarkers, and possible antioxidant
therapies in CKD patients.
Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia.
We investigated whether plasma ω-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG).
This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline ω-3 fatty acid concentrations.
There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3 fatty acids (>590 μmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (<390 μmol/L). High baseline ω-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group.
The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids. It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials. This trial was registered at www.controlled-trials.com as ISRCTN94410159.
© 2015 American Society for Nutrition.
Fatigue is a predictor of cardiovascular events in patients with end-stage renal disease (ESRD) undergoing hemodialysis treatment. We hypothesized that multinutritional support would improve quality of life, fatigue symptoms, and potential quantitative measures including endocrine, immune and autonomic functions in patients with ESRD undergoing hemodialysis.
Two hundred and two hemodialysis patients were randomly assigned to receive active treatment (containing vitamin B1, vitamin B2, niacin, vitamin B6, vitamin B12, folic acid, vitamin C, carnitine, coenzyme Q10, naïve galacto-oligosaccharide, and zinc) or placebo after each dialysis session for 12 weeks. The patients and attending physicians were blinded to the treatment, and 172 patients (86 in each group) completed the study. Fatigue was evaluated via fatigue questionnaire at 0, 4, and 12 weeks. To assess human herpes virus (HHV) 6 and 7 reactivation, numbers of viral DNA copies were determined in saliva by polymerase chain reaction at weeks 0 and 12. Autonomic function was determined via measurement of beat-to-beat variation by using acceleration plethysmography.
Clinical characteristics, changes in fatigue, quality of life score, endocrine functions, and laboratory data did not differ significantly between the two groups. Several parameters of heart rate variability significantly increased after nutritional treatment compared to placebo. Nutritional drink for 12 weeks significantly suppressed HHV7 DNA copy numbers. Similarly, HHV6 DNA copy numbers tended to be decreased by treatment but without reaching statistical significance.
Nutritional supplementation may modulate immune and autonomic dysfunction in ESRD patients undergoing hemodialysis.
Protein malnutrition has a negative effect on body composition and some blood parameters, especially
in the young growing organism. One of nutritional factors which could protect against negative
consequences of protein deficiency may be B group vitamins. The aim of the study was to investigate
the effect of vitamin B12 supplementation on the immune system in rats fed a standard and a low-protein
diet. Rats were fed a control (20% of energy from protein) or a protein-deficient diet (4.5% of energy
from protein). Half of animals in each group were additionally supplemented with vitamin B12 (300%
of the daily intake). The white blood cells analysis and lymphocytes immunophenotyping (number and
percentage) were performed. Low-protein diets caused disturbances in WBC and lymphocyte subpopulations
in both short- (30-day) as well as long-term periods (90-day). Vitamin B12 supplementation
significantly reduced the negative impact of protein malnutrition after 30 days, however had no effect
on long-term malnutrition. Furthermore, vitamin B12 addition in rats fed a control diet did not affect
the studied parameters. This observation opens the promise of use of vitamin B12 supplementation to
improve immune system parameters in protein malnourished organisms.
The B vitamins folic acid, vitamin B12 and B6 are essential for neuronal function, and severe deficiencies have been linked to increased risk of neurodevelopmental disorders, psychiatric disease and dementia. Polymorphisms of genes involved in B vitamin absorption, metabolism and function, such as methylene tetrahydrofolate reductase (MTHFR), cystathionine β synthase (CβS), transcobalamin 2 receptor (TCN2) and methionine synthase reductase (MTRR), have also been linked to increased incidence of psychiatric and cognitive disorders. However, the effects of these polymorphisms are often quite small and many studies failed to show any meaningful or consistent associations. This review discusses previous findings from clinical studies and highlights gaps in knowledge. Future studies assessing B vitamin-associated polymorphisms must take into account not just traditional demographics, but subjects’ overall diet, relevant biomarkers of nutritional status and also analyze related genetic factors that may exacerbate behavioral effects or nutritional status.
Few B-vitamin trials to lower homocysteine (Hcy) have reported evidence of beneficial effects on cognition in older adults with cognitive impairment or Alzheimer's disease. This article reviews the role of Hcy in cognitive decline. It also considers some reasons why meta-analyses have failed to find effects of B-vitamin treatment. Findings from the successful VITACOG trial are examined from a new perspective of critical levels of Hcy and brain atrophy that may impact on the efficacy of B-vitamin treatment. It appears that there is a critical level of brain shrinkage, possibly mediated by elevated Hcy, which when reached, results in cognitive decline, especially in episodic memory performance. Supplements, food sources, and effects of folic acid fortification are discussed in relation to B12 deficiency.
Different vitamin B12 and folic acid concentrations could exacerbate the immune response. The aim was to evaluate different dietary folic acid and vitamin B12 levels on the immune response in aged rats. Male Sprague Dawley aged rats were assigned to three folic acid groups (deficient, control, supplemented) each in absence of vitamin B12 for 30 days. Several parameters of innate and acquired immune responses were measured. Serum and hepatic folate levels increased according to folic acid dietary level, while vitamin B12 levels decreased. There was a significant decrease in natural killer cell-mediated cytotoxicity in the spleen for the vitamin B12 deficient diet and folic acid control diet groups. Significant changes in CD45 lymphocyte subsets were also observed according to dietary imbalance. Lymphoproliferative response to concanavalin A and phytohemagglutinin did not differ significantly between groups. The spleen response to lipopolysaccharide increased significantly, but was unmodified for the other organs. An imbalance between dietary vitamin B12 and folic acid concentrations alters some immunological parameters in aged rats. Therefore, the ratio between folate and vitamin B12 could be as important as their absolute dietary concentrations.
Background & aims:
Several authors have reported low folate intake in patients with eating disorders (ED). This vitamin plays an essential role in synthesis reactions for neurotransmitters and structural elements of neurons, and therefore its deficiency has been associated with the presence of different disorders linked to mental function. The aim of this study was to determine the effect of folic acid supplementation on homocysteine levels and the cognitive and depressive status of a group of patients with eating disorders with low folate intake.
Subjects/methods:
The study was designed as a randomised, prospective clinical trial, which included 24 participants assigned to two treatment groups for six months: supplemented group (SG) (10 mg/day of folic acid [ACFOL]) and a placebo group (PG). Both groups maintained their medical, dietary and psychological treatment. At baseline and end of the intervention, anthropometric, dietary and biochemical parameters (plasma homocysteine [Hcy], serum and red blood cell folate) were recorded. Cognitive and depressive status questionnaires were administered (Stroop Test, Trail Making Test and Beck Depression Inventory).
Results:
Twenty-two patients completed the study (SG: 12, PG: 10, mean age: 24.2 ± 8.8 years, BMI 18.9 ± 3.5 kg/m2). The SG significantly increased their serum and red blood cell folate levels and lowered Hcy levels (9.4 ± 2.4 μmol/l vs. 7.5 ± 1.7 μmol/l, P < 0.01). The SG also significantly improved most of their test scores for cognitive and depressive status. The PG showed no significant changes in any of the evaluated variables.
Conclusions:
The results show that folic acid supplementation may be used as another tool within the comprehensive and multidisciplinary treatment applied to patients with ED.
Background:
Inflammation underlies the etiology of colorectal cancer (CRC). Hyperhomocysteinemia is associated with inflammation and may be a risk marker for CRC. Cysteine is a metabolic product of homocysteine and a precursor of the antioxidant glutathione. It is unknown whether cysteine is associated with CRC.
Objective:
The objective was to assess the associations between homocysteine and cysteine and CRC incidence in postmenopausal women.
Design:
Associations between homocysteine and cysteine and incident CRC in the Women's Health Initiative observational cohort were assessed by using a nested case-control design. Cases and controls (n = 988/group) were matched for age (mean ± SD age: 67 ± 7 y), ethnicity (85.2% white, 8.9% black, 2.2% Hispanic/Latina, and 3.6% other), hysterectomy status, and date of blood draw. Homocysteine and cysteine were measured by HPLC with postcolumn fluorimetric detection.
Results:
Multivariate-adjusted ORs (95% CIs) for CRC were 1.46 (1.05, 2.04) for the highest quartile of homocysteine (>9.85 μmol/L) compared with the lowest quartile (≤6.74 μmol/L) (P = 0.02) and 0.57 (0.40, 0.82) for the highest quartile of cysteine (>309 μmol/L) compared with the lowest quartile (≤260 μmol/L) (P = 0.01). The association with homocysteine was significant for proximal colon tumors (P = 0.008) but not for distal or rectal tumors, whereas the association with cysteine was significant for rectal tumors (P = 0.02), borderline for proximal tumors (P = 0.06), and not significant for distal tumors. The associations with both homocysteine and cysteine were significant for localized tumors (P ≤ 0.01) but not for metastases.
Conclusion:
High plasma homocysteine is associated with increased risk of CRC, whereas high cysteine is associated with decreased risk. This trial was registered at clinicaltrials.gov as NCT 00000611.
Dietary factors regulate immunological function, but the underlying mechanisms remain elusive. Here we show that vitamin B9 is a survival factor for regulatory T (Treg) cells expressing high levels of vitamin B9 receptor (folate receptor 4). In vitamin B9-reduced condition in vitro, Treg cells could be differentiated from naïve T cells but failed to survive. The impaired survival of Treg cells was associated with decreased expression of anti-apoptotic Bcl2 and independent of IL-2. In vivo depletion of dietary vitamin B9 resulted in the reduction of Treg cells in the small intestine, a site for the absorption of dietary vitamin B9. These findings provide a new link between diet and the immune system, which could maintain the immunological homeostasis in the intestine.
Dear Sir,
Dr Adams has certainly challenged conventional thinking with his review in the October QJM . Cholesterol has always been a fascinating and star subject. Some 13 scientists have been awarded Nobel prizes for studies on cholesterol, its structure and physiology. Brown and Goldstein in their Nobel Prize Lecture described cholesterol as the ‘the most highly decorated small molecule …
This study aimed to examine the association of dietary vitamin intakes with plasma pro-inflammatory cytokine levels in Korean heart failure patients. Stable outpatients with heart failure were recruited and finally 91 patients were included. Dietary intakes were estimated by a developed semi-quantitative food frequency questionnaire. The simultaneous measurement of 17 cytokines was performed along with analysis of plasma C-reactive protein. Plasma C-reactive protein levels significantly correlated with dietary intakes of vitamin C (r = -0.30, p<0.005), β-carotene (r = -0.23, p<0.05), and folate (r = -0.31, p<0.005). However, these associations were no longer significant after adjusting for traditional risk factors for heart failure. On the other hand, plasma levels of monocyte chemoattractant protein-1 significantly correlated with dietary folate intake (r = -0.31, p<0.001), and plasma interleukin-8 levels significantly correlated with dietary intakes of vitamin C (r = -0.38, p<0.001), β-carotene (r = -0.42, p<0.001), and folate (r = -0.38, p<0.001) after the adjustment. Dietary folate intake was found as a primary influencing factor on plasma levels of monocyte chemoattractant protein-1 (p<0.005, R(2) = 0.20) and interleukin-8 (p<0.001, R(2) = 0.32) through a stepwise multiple linear regression analysis. Dietary folate intake was significantly associated with plasma levels of monocyte chemoattractant protein-1 and interleukin-8 which indicates dietary folate may have a potentially beneficial role in the prevention and treatment of heart failure.
Background: In cross-sectional studies, elevated plasma total homocysteine (tHcy) concentrations have been associated with cognitive impairment and dementia. Incidence studies of this issue are few and have produced conflicting results.
Objective: We investigated the relation between high plasma tHcy concentrations and risk of dementia and Alzheimer disease (AD) in an elderly population.
Design: A dementia-free cohort of 816 subjects (434 women and 382 men; mean age: 74 y) from an Italian population-based study constituted our study sample. The relation of baseline plasma tHcy to the risk of newly diagnosed dementia and AD on follow-up was examined. A proportional hazards regression model was used to adjust for age, sex, education, apolipoprotein E genotype, vascular risk factors, and serum concentrations of folate and vitamin B-12.
Results: Over an average follow-up of 4 y, dementia developed in 112 subjects, including 70 who received a diagnosis of AD. In the subjects with hyperhomocysteinemia (plasma tHcy > 15 μmol/L), the hazard ratio for dementia was 2.08 (95% CI: 1.31, 3.30; P = 0.002). The corresponding hazard ratio for AD was 2.11 (95% CI: 1.19, 3.76; P = 0.011). Independently of hyperhomocysteinemia and other confounders, low folate concentrations (≤11.8 nmol/L) were also associated with an increased risk of both dementia (1.87; 95% CI: 1.21, 2.89; P = 0.005) and AD (1.98; 95% CI: 1.15, 3.40; P = 0.014), whereas the association was not significant for vitamin B-12.
Conclusions: Elevated plasma tHcy concentrations and low serum folate concentrations are independent predictors of the development of dementia and AD.
Background: Elevated homocysteine concentrations may contribute to cognitive impairment. Most elevations in homocysteine result from inadequate folate, vitamin B-12, or vitamin B-6 intake. It is not clear whether the observed associations between homocysteine and cognitive measures are causal or whether they are due to homocysteine, to independent actions of the B vitamins, or to both.
Objective: We aimed to assess the individual and independent effects of baseline plasma homocysteine, folate, vitamin B-12, and vitamin B-6 and of dietary B vitamin intakes on 3-y changes in cognitive measures in 321 aging men.
Design: Participants were from the Veterans Affairs Normative Aging Study. Cognitive function was assessed with the Mini-Mental State Examination and on the basis of measures of memory, verbal fluency, and constructional praxis, which were adapted from the revised Wechsler Adult Intelligence Scale and the Consortium to Establish a Registry for Alzheimer’s Disease batteries at 2 time points. At baseline, dietary intakes were assessed with a food-frequency questionnaire, and blood was drawn for the measurement of B vitamins and homocysteine.
Results: Over a mean 3-y follow-up, declines in constructional praxis, measured by spatial copying, were significantly associated with plasma homocysteine, folate, and vitamins B-6 and B-12 and with the dietary intake of each vitamin. Folate (plasma and dietary) remained independently protective against a decline in spatial copying score after adjustment for other vitamins and for plasma homocysteine. Dietary folate was also protective against a decline in verbal fluency. A high homocysteine concentration was associated with a decline in recall memory.
Conclusions: Low B vitamin and high homocysteine concentrations predict cognitive decline. Spatial copying measures appear to be most sensitive to these effects in a general population of aging men.
Yeast based spreads (YBS) such as marmite and vegemite, made from leftover brewer’s yeast extract are one of the world’s richest source of B vitamins. We evaluated symptoms of depression, anxiety, stress scores (DASS) in participants who consume or do not consume YBS. 520 participants completed a survey consisting of 70–94 questions relating to the consumption of YBS, dietary and lifestyle habits and mood symptoms of DASS. Parametric analysis co-varying for gender, diet, supplement use, soy milk and alcohol consumption and history of psychiatric disorders including depression and anxiety were utilized to analyse the results. A significant improvement was noted in anxiety and stress but not depressive symptoms in those consuming YBS. Furthermore, those who consumed vitamin B12 fortified YBS showed even greater improvement in stress symptomology. Vitamin B supplementation appears to be an important additive supplementary source to improved stress and anxiety in the general adult population.
Background:
Damage to the myelin sheath (demyelination) is one of the main manifestations of multiple sclerosis (MS). Interestingly, both MS and vitamin B deficiency results in severe myelin degeneration that leads to loss in neuronal signal transmission.
Objective:
Deficiency in vitamin B complex vary, although common symptoms include fatigue, increased oxidative stress, inflammation and demyelination. In particular, vitamin B12 (cobalamin) has had increased attention for its role in the methylation process, involvement in myelination and re-myelination, and reversal of MS symptoms.
Method:
Here, we discuss the role of vitamin B complex (B1, B2, B3, B4, B5, B6, B7, B9, B12) in MS.
Results:
The anti-inflammatory and re-myelinating attributes of vitamin B complex members are promising, despite limited clinical studies.
Conclusion:
There is an urgent need for larger studies to determine the role of vitamin B supplementation alone, or in combination with other therapeutic agents, in prevention or reversal of MS, and aid in improved quality of life of MS patients.
Elevated plasma homocysteine is an independent risk factor for atherosclerosis and thrombosis. The exact mechanism by which homocysteine exerts its atherothrombotic action is still unclear. Accumulating evidence suggests that hyperhomocysteinaemia leads to endothelial injury and dysfunction, mediated by free radicals generated during the oxidation of homocysteine. Homocysteine also stimulates the proliferation of vascular smooth-muscle cells and inhibits the growth of vascular endothelial cells. Elevated homocysteine levels may also promote thrombosis by increased generation of thrombin. Other possible mechanisms for homocysteine-mediated atherogenesis include: The altered methylation of DNA and altered regulatory proteins associated with cell membrane, decreased bioavailability of nitric oxide, increased elastolysis and collagen accumulation, overstimulation of N-methyl-D-aspartate receptors and excessive adhesion of monocytes and neutrophils to endothelium. Understanding the mechanisms in vivo by which hyperhomocysteinaemia is associated with vascular disease may provide new approaches to prevention and treatment of atherothrombosis. ∗∗∗J Cardiovasc Risk 5:239-247 © 1998 Lippincott Williams & Wilkins.
Methamphetamine (METH) is a powerful central nervous system stimulant which elevates mood, alertness, energy levels and concentration in the short-term. However, chronic use and/or at higher doses METH use often results in psychosis, depression, delusions and violent behavior. METH was formerly used to treat conditions such as obesity and attention deficit hyperactivity disorder, but now is primarily used recreationally. Its addictive nature has led to METH abuse becoming a global problem. At a cellular level, METH exerts a myriad of effects on the central and peripheral nervous systems, immune system and the gastrointestinal system. Here we present how these effects might be linked and their potential contribution to the pathogenesis of neuropsychiatric disorders. In the long term, this pathway could be targeted therapeutically to protect people from the ill effects of METH use. This model of METH use may also provide insight into how gut, nervous and immune systems might break down in other conditions that may also benefit from therapeutic intervention.
(Cell Metabolism 25, 345–357; February 7, 2017) As a result of an author oversight in the originally published version of this article, the Supplemental Information was published with two data tables missing. These missing tables have now been added to the Supplemental Information and appear with the article online. The authors apologize for the error and any inconvenience it may have caused.
During immune challenge, T lymphocytes engage pathways of anabolic metabolism to support clonal expansion and the development of effector functions. Here we report a critical role for the non-essential amino acid serine in effector T cell responses. Upon activation, T cells upregulate enzymes of the serine, glycine, one-carbon (SGOC) metabolic network, and rapidly increase processing of serine into one-carbon metabolism. We show that extracellular serine is required for optimal T cell expansion even in glucose concentrations sufficient to support T cell activation, bioenergetics, and effector function. Restricting dietary serine impairs pathogen-driven expansion of T cells in vivo, without affecting overall immune cell homeostasis. Mechanistically, serine supplies glycine and one-carbon units for de novo nucleotide biosynthesis in proliferating T cells, and one-carbon units from formate can rescue T cells from serine deprivation. Our data implicate serine as a key immunometabolite that directly modulates adaptive immunity by controlling T cell proliferative capacity.
Increasing evidence indicates that there are various interactions between the nervous system and the immune system, and that the immune system plays an important role in the pathogenesis of depression. Pro-inflammatory cytokines (such as IL-1, IL-6, TNF-α) have been implicated in the neurobiological manifestations of depression. The immune/cytokine network has a powerful influence on the brain. In addition, deficiency in B vitamins has been linked to depression. Hence, greater knowledge of how immune cells change in the presence of vitamin B derivatives could improve understanding of how immune changes may correlate with depression, all of which are discussed herein.
The recent increase in the intake of folic acid by the general public through fortified foods and supplements, has raised safety concern based on early reports of adverse health outcome in elderly with low B12 status who took high doses of folic acid. These safety concerns are contrary to the 2015 WHO statement that “high folic acid intake has not reliably been shown to be associated with negative healeffects”. In the folic acid post-fortification era, we have shown that in elderly participants in NHANES 1999-2002, high plasma folate level is associated with exacerbation of both clinical (anemia and cognitive impairment) and biochemical (high MMA and high Hcy plasma levels) signs of vitamin B12 deficiency. Adverse clinical outcomes in association with high folate intake were also seen among elderly with low plasma B12 levels from the Framingham Original Cohort and in a study from Australia which combined three elderly cohorts. Relation between high folate and adverse biochemical outcomes were also seen in the Sacramento Area Latino Study on Aging (High Hcy, high MMA and lower TC2) and at an outpatient clinic at Yale University where high folate is associated with higher MMA in the elderly but not in the young.
Aim:
Disorders in the metabolism of homocysteine and B vitamins, which are involved in a one-carbon transfer reaction and important for DNA synthesis and methylation, have been hypothesized to be associated with carcinogenesis. The purpose of this study is to evalu-ate the levels of homocysteine, vitamin B12 and folic acid in patients with newly diagnosed lung cancer and determines whether they might be used as an accurate tumor marker for monitoring the patients if they are found to be elevated in lung cancer.
Materials and methods:
Forty male patients with lung cancer were included in this study. Age-matched forty healthy males who had not malignant disease or had not received any drug affecting plasma homocysteine levels were selected as control group. Homocysteine, vitamin B12 and folate levels were measured in the samples obtained from the patients and controls.
Results:
Mean age of the patients with lung cancer was 58.7 ± 9.9 years. All the patients were cigarettes smokers. Mean daily consumption of cigarettes was 2.0±0.7 packs and mean duration of smoking was 30 ± 11 years. Histologic type of carcinoma was found to be squamous cell carcinoma in 55%, adenocarcinoma - in 35%, and small cell carcinoma - in 10% of the cases. Clinical stage was stage IA in 20%, stage IB - in 20%, stage IIA - in 2.5%, stage IIB - in 10%, stage IIIA - in 12.5%, stage IIIB - in 20%, and stage IV - in 15% of the cases. Mean homocysteine level was 15.3 ± 7.3 µmol/l in the patients with lung cancer while 9.8 ± 2.6 µmol/l in controls. Homocysteine level was significantly higher in the patients with lung cancer compared to control group (p < 0.001). Mean folate level was 4.3 ± 1.8 pg/ml in cancer cases while 6.1 ± 2.3 pg/ml in controls. That is to say, plasma folate levels were significantly lower in cases of lung cancer compared to controls (p < 0.001). There was no significantly difference between groups with regard to B12 levels (mean B12 level was 234 ± 99 and 240 ± 104 ng/ml in the patients with lung cancer and controls, respectively, p = 0.78). Plasma homocysteine, vitamin B12 and folate levels did not show significant difference with respect to histologic type of carcinoma. No significant correlation was found between plasma homocysteine, vitamin B12, folate levels and number of cigarettes smoked per day, duration of smoking, age of the patient, and clinical stage of carcinoma. There was also no correlation between number of cigarettes smoked per day, duration of smoking, age of the patient and clinical stage of carcinoma. A possible inverse correlation between plasma homocysteine, vitamin B12 and folate levels was not observed.
Conclusion:
In conclusion, high plasma homocysteine and low folate levels could be associated with lung cancer. However, further studies performed on large patient population are needed.
The risk of osteoporosis and bone fractures increases with age. Several other factors are also related to bone disease including gender, race/ethnicity, physical activity, alcohol, smoking, estrogen, and calcium and vitamin D. B-vitamins (folate, B12, and B6) are also emerging dietary factors related to bone health, both individually and through their action on influencing total plasma homocysteine concentrations (tHcy). The primary objective of this review is to summarize the available data on B-vitamins and bone health, highlighting clinical trials and observational data. In populations without folic acid fortification, the totality of evidence suggests that elevated tHcy has a small but significant association with bone fracture risk and bone quality but not on bone mineral density (BMD) or bone turnover biomarkers. Very little supportive evidence exists for a direct role of folate for either BMD or fracture risk; however, the data available are quite limited. Meta-analyses and some cross-sectional and cohort studies suggest a small but significant role of vitamin B12 status on risk of fracture but not on BMD. The mechanism by which tHcy and B12 may influence bone health is not well characterized but may be through modulation of collagen cross-linking or through altering osteoclasts or osteoblasts. Much more data are needed-particularly the role that each vitamin directly has on bone, or whether the vitamins only exert their effect though tHcy concentrations. Nevertheless, consistent findings across different populations with different study designs suggest a role for tHcy and B12 in reducing fracture risk.
It is well known that neuronal damage following a stroke has been attributed to the over stimulation of excitatory amino acids such as glutamate and aspartate through activation of NMDA receptors. The brain is exposed to most of the constituents of plasma including homocysteine as a result of the disruption of the blood–brain barrier after stroke, head trauma and stress. The question, therefore, arises as to whether or not homocysteine is able to selectively stimulate the release of excitatory amino acids in stroke. This review article will address the importance of homocysteine in nervous system specifically how these amino acids may trigger the release of catecholamines. Our data will thus strengthen the view that a mechanism for the association of hyperhomocysteinemia with increased brain lesion in stroke. As hypothalamus also controls the cardiac function via sympathetic system, the contractility of heart will be compromised. Homocysteine is also known to mediate cardiovascular problems by its adverse effects on cardiovascular endothelium and smooth muscle cells with resultant alterations in subclinical arterial structure and function. The present review will thus summarize both central and peripheral effects of homocysteine and will highlight some of the controversies associated with hyperhomocysteinemia-induced cardiovascular problems.
Introduction:
In some previous studies, vitamin B12 treatment showed immunomodulatory effects and restored the immunological abnormalities in patients with pernicious anemia (PA). In the present study, peripheral blood T cell subsets, including regulatory T cells (T(reg)s), were examined before and after vitamin B12 treatment in PA patients.
Patients and methods:
The percentages of CD4, CD8, Th1, Th2 and T(reg)s were examined in 23 PA patients before vitamin B12 treatment, in 23 other PA patients after vitamin B12 treatment and in 28 healthy controls.
Results:
The mean percentage of CD8+ T cells was significantly higher in the control group (23.0%; 95% CI, 20.4-25.6%) than in the pre- (16.0%; 95% CI, 12.1-20.0%) and posttreatment groups (15.2%; 95% CI, 11.8-18.6%; p < 0.05). The CD4/CD8 ratio was significantly lower in the control group (2.01; 95% CI, 1.66-2.34) than in the pre- (3.45; 95% CI, 2.55-7.80) and posttreatment groups (2.97; 95% CI, 2.22-3.72; p < 0.05). There was no significant difference in the mean Th1/Th2 ratio among these groups. There were significant increases in the mean percentage of T(reg)s in the pre- (6.29%; 95% CI, 5.04-7.54%) and posttreatment groups (7.77%; 95% CI, 6.34-9.20%) compared with the control group (4.18%; 95% CI, 3.92-4.47%; p < 0.05).
Conclusions:
The percentage of T(reg)s was significantly higher in PA patients than in normal subjects, and this high T(reg) percentage was not different before and after vitamin B12 treatment. Other immunological alterations also did not recover after vitamin B12 treatment, so that these immunological changes appear to be the cause of PA and are not induced by vitamin B12 deficiency.
Homocysteine (Hcy) is an endogenous, non-structural protein, a sulfur-containing amino acid emerging on the pathway of methionine and cysteine, actively involved in numerous biochemical reactions. Total concentration of homocysteine in plasma of healthy humans is low and its level is between 5.0 and 15.0 mmol/l, assessed with the use of HPLC, or 5.0-12.0 mmol/l, using immunoassay methods. Higher concentration of this amino acid in blood is called hyperhomocysteinemia. Hyperhomocysteinemia is significantly correlated with cardiovascular disease and its complications: heart attacks and strokes. It is believed that hyperhomocysteinemia damages endothelial cells, reduces the flexibility of vessels, and adversely affects the process of hemostasis. In addition, hyperhomocysteinemia enhances the adverse effects of risk factors such as hypertension, smoking, and impaired glucose, lipid and lipoprotein metabolism, as well as promoting the development of inflammation. The concentration of homocysteine can be effectively lowered by supplementation with folic acid and vitamins B12 and B6. However, intervention studies conducted in the past decade did not confirm the clinical benefit of vitamin therapy lowering the level of homocysteine in blood of patients with cardiovascular disease. Moreover, there is not clear evidence from genetic studies that the presence of the gene for MTFHR polymorphism 677C>T, which is one of the most common causes of hyperhomocysteinemia, is also associated with the development of cardiovascular disease. These results led the researchers to discuss the role of homocysteine in the development and treatment of cardiovascular disease as well as the need for further research on this issue.
Alzheimer's disease (AD), vascular dementia (VaD) and mixed dementia (MD) are the most common dementia diseases among the elderly. Currently, there is no effective treatment of these diseases and, therefore, it seems justified to develop the principles of prevention, taking into account the elimination of risk factors. Among them folic acid deficiency may play an important role.
To evaluate possible relationship of folate deficiency with the development of selected dementia diseases: vascular dementia (VaD), Alzheimer's disease (AD), mixed dementia (MD).
The study involved 166 people, including 47 people with the diagnosis of AD, 41 with VaD and 36 with MD. The control group consisted of 42 persons without cognitive impairment. All patients underwent a general physical, neurological, psychiatric and extensive neuropsychological examination, as well as routine blood and biochemical screening tests and neuroimaging. The level of serum folate (Fol) was measured by electrochemiluminescence immunoassay. To assess the correlation of Fol level with the cognitive impairment neuropsychometric scales: Mini Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) were used.
In patients with dementia, compared with the control group, there were significantly lower levels of folic acid (p = 0.04). There was no difference in the concentration of Fol in groups of patients (p = 0.0889). In people without cognitive impairment (CDR 0) levels of folic acid were significantly higher compared to the group with moderate dementia (CDR 2, p = 0.0475).
The results may suggest that folic acid deficiency is one of the possible causes of dementia, but does not determine its type. Determination of serum Fol in the elderly and supplementation of this vitamin deficiency may play an important role in the prevention of the most common dementias.
The advanced lesions of atherosclerosis represent the culmination of a specialized form of chronic inflammation followed by a fibroproliferative process that takes place within the intima of the affected artery. Proliferation of smooth muscle cells and generation of connective tissue occur. Proliferation results from interactions between arterial smooth muscle, monocyte-derived macrophages, T lymphocytes, and endothelium. The initial lesion of atherosclerosis, the fatty streak, begins as an accumulation of monocytederived macrophages and T lymphocytes, which adhere and migrate into the intima of the affected artery. Smooth muscle cells, which are present in the intima or which migrate into the intima from the media, then replicate. Monocyte-derived macrophages and T cells also replicate during lesion formation and progression due to the production of cytokines and growth-regulatory molecules. These molecules determine whether there is proliferation and lesion progression or inhibition of proliferation and lesion regression. Several growthregulatory molecules may play critical roles in this process, including platelet-derived growth factor (PGDF), transforming growth factor beta, fibroblast growth factor, heparinbinding epidermal growth factor-like growth factor, and others. PDGF may be one of the principal components in this process because protein containing the PDGF B-chain has been demonstrated within activated lesion macrophages during every phase of atherogenesis. The presence of this growth factor and its receptors on lesion smooth muscle cells creates opportunities for smooth muscle chemotaxis and replication. Smooth muscle proliferation depends upon a series of complex signals based upon cellular interactions in the local microenvironment of the artery. The intracellular signalling pathways for mitogenesis versus chemotaxis are being investigated for smooth muscle. The roles of the cytokines and growth-regulatory peptides involved in these cellular interactions represent critical points of departure for intervention and the development of new diagnostic methods. In addition, magnetic resonance imaging has been developed to demonstrate the fine structure of lesions of atherosclerosis in peripheral arteries not subject to cardiac motion. This noninvasive methodology holds great promise for the future of these approaches.
Abstract Bone remodeling is a very complex process. Homocysteine (Hcy) is known to modulate this process via several known mechanisms such as increase in osteoclast activity, decrease in osteoblast activity and direct action of Hcy on bone matrix. Evidence from previous studies further support a detrimental effect on bone via decrease in bone blood flow and an increase in matrix metalloproteinases (MMPs) that degrade extracellular bone matrix. Hcy binds directly to extracellular matrix and reduces bone strength. There are several bone markers that can be used as parameters to determine how high levels of plasma Hcy (hyperhomocysteinemia, HHcy) affect bone such as: hydroxyproline, N-terminal collagen 1 telopeptides. Mitochondrion serves an important role in generating reactive oxygen species (ROS). Mitochondrial abnormalities have been identified during HHcy. The mechanism of Hcy-induced bone remodeling via the mitochondrial pathway is largely unknown. Therefore, we propose a mitochondrial mechanism by which Hcy can contribute to alter bone properties. This may occur both through generations of ROS that activate MMPs and could be extruded into matrix to degrade bone matrix. However, there are contrasting reports on whether Hcy affects bone density, with some reports in favour and others not. Earlier studies also found an alteration in bone biomechanical properties with deficiencies of vitamin B12, folate and HHcy conditions. Moreover, existing data opens speculation that folate and vitamin therapy act not only via Hcy-dependent pathways but also via Hcy-independent pathways. However, more studies are needed to clarify the mechanistic role of Hcy during bone diseases.
B-vitamin deficiency is a risk factor for vascular disease. The mechanism by which the deficiency impacts on disease risk is unclear. We have analysed whether the inflammatory response of mononuclear cells can be modified by cellular folate status in vitro. We show that the mouse monocyte cell line RAW264.7 grown under folate restriction displays a decrease in intracellular folate levels and a reduced growth rate. The cells also show a 2- to 3-fold increase in expression of the inflammatory mediators, IL1β, IL6, TNFα and MCP1 at the RNA and protein level (p<0.01) under conditions of folate deficiency. In contrast the production of the vaso-protective mediator nitric oxide is significantly reduced under these conditions. These metabolic changes are independent of the concentration of homocysteine in the medium and occur in the absence of significant changes in global DNA methylation. Folate deficiency may therefore exacerbate cardiovascular disease by augmenting pro-inflammatory signals in the monocyte-macrophage lineage.
Evidence remains unclear as to whether folic acid (FA) and vitamin B-12 supplementation is effective in reducing depressive symptoms.
The objective was to determine whether oral FA + vitamin B-12 supplementation prevented cognitive decline in a cohort of community-dwelling older adults with elevated psychological distress.
A randomized controlled trial (RCT) with a completely crossed 2 × 2 × 2 factorial design comprising daily oral 400 μg FA + 100 μg vitamin B-12 supplementation (compared with placebo), physical activity promotion, and depression literacy with comparator control interventions for reducing depressive symptoms was conducted in 900 adults aged 60-74 y with elevated psychological distress (Kessler Distress 10-Scale; scores >15). The 2-y intervention was delivered in 10 modules via mail with concurrent telephone tracking calls. Main outcome measures examined change in cognitive functioning at 12 and 24 mo by using the Telephone Interview for Cognitive Status-Modified (TICS-M) and the Brief Test of Adult Cognition by Telephone (processing speed); the Informant Questionnaire on Cognitive Decline in the Elderly was administered at 24 mo.
FA + vitamin B-12 improved the TICS-M total (P = 0.032; effect size d = 0.17), TICS-M immediate (P = 0.046; d = 0.15), and TICS-M delayed recall (P = 0.013; effect size d = 0.18) scores at 24 mo in comparison with placebo. No significant changes were evident in orientation, attention, semantic memory, processing speed, or informant reports.
Long-term supplementation of daily oral 400 μg FA + 100 μg vitamin B-12 promotes improvement in cognitive functioning after 24 mo, particularly in immediate and delayed memory performance. This trial was registered at clinicaltrials.gov as NCT00214682.
Supplementation with folate may help reduce depressive symptoms. Folate, a naturally occurring B vitamin, is needed in the brain for the synthesis of norepinephrine, serotonin, and dopamine. Three forms of folate are commonly used: folic acid, 5-methyltetrahydrofolate (5-MTHF) (also known as methylfolate and L-methylfolate), and folinic acid. Some forms may be more bioavailable than others in patients with a genetic polymorphism and in those who take particular medications or use alcohol. Folic acid augmentation in depressed patients may reduce residual symptoms. The 5-MTHF formulation indicated efficacy as adjunctive therapy or monotherapy in reducing depressive symptoms in patients with normal and low folate levels, improving cognitive function and reducing depressive symptoms in elderly patients with dementia and folate deficiency, and reducing depressive and somatic symptoms in patients with depression and alcoholism. Adjunctive folinic acid reduced depressive symptoms in patients who were partially responsive or nonresponsive to a selective serotonin reuptake inhibitor. Evidence for the efficacy of folate in improving cognitive symptoms is equivocal, but most studies used folic acid. Although the studies reviewed have limitations and, historically, concerns have been raised about the role of folate in increasing cancer risk, masking B(12) deficiency, and worsening depressive symptoms, folate is generally well tolerated, and 5-MTHF may be less likely to incur some of these risks. Several forms of folate appear to be safe and efficacious in some individuals with major depressive disorder, but more information is needed about dosage and populations most suited to folate therapy.