Chronic micronutrient deficiency

Contribution of Selected Vitamins and Trace Elements to Immune Function

Type of study:

Number of citations: 724

Year: 2007

Authors: E. Wintergerst, S. Maggini, D. Hornig

Journal: Annals of Nutrition and Metabolism

Journal ranking: Q2

Key takeaways: Adequate intake of vitamins and trace elements, particularly antioxidants, supports immune function and reduces susceptibility to infections.

Abstract: Adequate intakes of vitamins and trace elements are required for the immune system to function efficiently. Micronutrient deficiency suppresses immune functions by affecting the innate T-cell-mediated immune response and adaptive antibody response, and leads to dysregulation of the balanced host response. This increases the susceptibility to infections, with increased morbidity and mortality. In turn, infections aggravate micronutrient deficiencies by reducing nutrient intake, increasing losses, and interfering with utilization by altering metabolic pathways. Insufficient intake of micronutrients occurs in people with eating disorders, in smokers (both active and passive), in individuals with chronic alcohol abuse, in patients with certain diseases, during pregnancy and lactation, and in the elderly. With aging a variety of changes are observed in the immune system, which translate into less effective innate and adaptive immune responses and increased susceptibility to infections. Antioxidant vitamins and trace elements (vitamins C, E, selenium, copper, and zinc) counteract potential damage caused by reactive oxygen species to cellular tissues and modulate immune cell function through regulation of redox-sensitive transcription factors and affect production of cytokines and prostaglandins. Adequate intake of vitamins B6, folate, B12, C, E, and of selenium, zinc, copper, and iron supports a Th1 cytokine-mediated immune response with sufficient production of proinflammatory cytokines, which maintains an effective immune response and avoids a shift to an anti-inflammatory Th2 cell-mediated immune response and an increased risk of extracellular infections. Supplementation with these micronutrients reverses the Th2 cell-mediated immune response to a proinflammatory Th1 cytokine-regulated response with enhanced innate immunity. Vitamins A and D play important roles in both cell-mediated and humoral antibody response and support a Th2-mediated anti-inflammatory cytokine profile. Vitamin A deficiency impairs both innate immunity (mucosal epithelial regeneration) and adaptive immune response to infection resulting in an impaired ability to counteract extracellular pathogens. Vitamin D deficiency is correlated with a higher susceptibility to infections due to impaired localized innate immunity and defects in antigen-specific cellular immune response. Overall, inadequate intake and status of these vitamins and minerals may lead to suppressed immunity, which predisposes to infections and aggravates malnutrition.

Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses

Type of study:

Number of citations: 562

Year: 2007

Authors: S. Maggini, E. Wintergerst, S. Beveridge, D. Hornig

Journal: British Journal of Nutrition

Journal ranking: Q1

Key takeaways: Adequate intake of selected vitamins and trace elements can support immune function by strengthening epithelial barriers, cellular and humoral immune responses, and reducing susceptibility to infections.

Abstract: Adequate intakes of micronutrients are required for the immune system to function efficiently. Micronutrient deficiency suppresses immunity by affecting innate, T cell mediated and adaptive antibody responses, leading to dysregulation of the balanced host response. This situation increases susceptibility to infections, with increased morbidity and mortality. In turn, infections aggravate micronutrient deficiencies by reducing nutrient intake, increasing losses, and interfering with utilization by altering metabolic pathways. Insufficient intake of micronutrients occurs in people with eating disorders, in smokers (active and passive), in individuals with chronic alcohol abuse, in certain diseases, during pregnancy and lactation, and in the elderly. This paper summarises the roles of selected vitamins and trace elements in immune function. Micronutrients contribute to the body's natural defences on three levels by supporting physical barriers (skin/mucosa), cellular immunity and antibody production. Vitamins A, C, E and the trace element zinc assist in enhancing the skin barrier function. The vitamins A, B6, B12, C, D, E and folic acid and the trace elements iron, zinc, copper and selenium work in synergy to support the protective activities of the immune cells. Finally, all these micronutrients, with the exception of vitamin C and iron, are essential for antibody production. Overall, inadequate intake and status of these vitamins and trace elements may lead to suppressed immunity, which predisposes to infections and aggravates malnutrition. Therefore, supplementation with these selected micronutrients can support the body's natural defence system by enhancing all three levels of immunity.

Vitamin B12, Folic Acid, and the Immune System

Type of study:

Number of citations: 44

Year: 2019

Authors: Kathleen Mikkelsen, V. Apostolopoulos

Journal: Nutrition and Immunity

Journal ranking: brak

Key takeaways: Inadequate levels of folic acid and vitamin B12 can significantly alter immune responses and contribute to various chronic diseases.

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.

The Effects of Vitamin D on Immune System and Inflammatory Diseases

Type of study: literature review

Number of citations: 239

Year: 2021

Authors: Tomoka Ao, J. Kikuta, M. Ishii

Journal: Biomolecules

Journal ranking: Q1

Key takeaways: Vitamin D deficiency is associated with an increased incidence or aggravation of infectious diseases and inflammatory autoimmune diseases, but its impact on treatment and prevention remains controversial.

Abstract: Immune cells, including dendritic cells, macrophages, and T and B cells, express the vitamin D receptor and 1α-hydroxylase. In vitro studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, has an anti-inflammatory effect. Recent epidemiological evidence has indicated a significant association between vitamin D deficiency and an increased incidence, or aggravation, of infectious diseases and inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, the impact of vitamin D on treatment and prevention, particularly in infectious diseases such as the 2019 coronavirus disease (COVID-19), remains controversial. Here, we review recent evidence associated with the relationship between vitamin D and inflammatory diseases and describe the underlying immunomodulatory effect of vitamin D.

The influence of Chosen Nutrients on Immune System Functioning Part II. Immunomodulatory Effects of Vitamins and Trace Elements on the Human Body

Type of study:

Number of citations: 10

Year: 2007

Authors: Monika Krzysik, J. Biernat, H. Grajeta

Journal: Advances in Clinical and Experimental Medicine

Journal ranking: Q1

Key takeaways: Deficiencies in vitamins, carotenoids, and trace elements can impair immune system function and lead to frequent infections.

Abstract: Deficiency of vitamins, carotenoids and trace elements in diet may impair the immunological responsiveness of organism. Micronutrients effect on immune system in multiple ways. Inadequate supply of vitamin A with diet may lead to lymphocyte dysfunction, whereas carotenoids supplementation may enhance the activity of natural killer cells and stimulate the production of various cytokines. Deficiencies of C and E vitamins in organism decrease inflammatory response and cause the phagocyte activity dysfunction. Vitamin E provides important antioxidants protection of cell membranes, vitamin C increases the number of CD4+ and CD8+ lymphocyte subpopulations in peripheral blood and stimulates macrophage migration. The research on immunosuppressing activity of vitamin D3 gives, in experimental phase, positive results in treatment of autoimmune diseases. Insufficient vitamin B supple− mentation in diet may impair humoral and cell−mediated immunity. Zinc, iron and selenium deficiencies may also impair immune response and lead to frequent infections. Zinc, for example, as a thymulin cofactor, directly effects the production, maturation and function of leucocytes (Adv Clin Exp Med 2007, 16, 1, 123–133).

Immunity, Vitamins and Nutrition

Type of study:

Number of citations: 2

Year: 2020

Authors: V. Delyagin

Journal:

Journal ranking: brak

Key takeaways: Nutrition plays a crucial role in maintaining immunity, with vitamin deficiency leading to disruption of immunity and increasing the risk of infectious diseases and autoimmune disorders.

Abstract: There is a relationship between nutrition and immunity. For developing countries, the problem – the protein-energy deficits, in developed and socially oriented economy – the lack of vitamins and trace elements. In Russia, various vitamins deficiency is registered in 30–90% of schoolchildren (from 20–40% to the extent of the deep deficit). Deficiency of vitamins and minerals leads to disruption of immunity raises the index of infectious diseases, autoimmune disorders. Insufficient supply of vitamins leads to a decrease in phagocytosis, proliferative activity of lymphocytes, decreased concentrations of C3 and C5 component of complement, IgG and secretory IgA, disintegrate physiological barriers. At the same time increases the concentration of pro-inflammatory cytokines. With a lack of selenium and vitamin E is possible passage of viruses from a sharp increase in virulence. The correction of micronutrient deficiencies should be combined, which implies the appointment of vitamin-mineral complexes with the inclusion of polyunsaturated fatty acids, choline. It is recommended the use of drugs, various forms of which are adapted to the age and the physiological needs of the child.

Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations

Type of study: non-rct experimental

Number of citations: 90

Year: 2017

Authors: Bingjun Qian, Shanqi Shen, Jianhua Zhang, P. Jing

Journal: Journal of Immunology Research

Journal ranking: Q1

Key takeaways: Vitamin B6 deficiency impairs immune cell differentiation, proliferation, and secretion, potentially weakening immunity, while appropriate supplementation could benefit immunity.

Abstract: The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immune response remains largely unknown. The aim of this study is to investigate the effects of vitamin B6 deficiency on the immune system through analysis of T lymphocyte differentiation, IL-2, IL-4, and INF-γ secretion, and SOCS-1 and T-bet gene transcription. We generated a vitamin B6-deficient mouse model via vitamin B6-depletion diet. The results showed that vitamin B6 deficiency retards growth, inhibits lymphocyte proliferation, and interferes with its differentiation. After ConA stimulation, vitamin B6 deficiency led to decrease in IL-2 and increase in IL-4 but had no influence on IFN-γ. Real-time PCR analysis showed that vitamin B6 deficiency downregulated T-bet and upregulated SOCS-1 transcription. This study suggested that vitamin B6 deficiency influenced the immunity in organisms. Meanwhile, the appropriate supplement of vitamin B6 could benefit immunity of the organism.

Regulatory role of vitamin E in the immune system and inflammation

Type of study:

Number of citations: 283

Year: 2018

Authors: E. Lewis, S. Meydani, Dayong Wu

Journal: IUBMB Life

Journal ranking: Q1

Key takeaways: Vitamin E supplementation enhances immune system function and reduces infection risk, particularly in older individuals, by modulating T cell function and reducing inflammation.

Abstract: Vitamin E, a potent lipid‐soluble antioxidant, found in higher concentration in immune cells compared to other cells in blood, is one of the most effective nutrients known to modulate immune function. Vitamin E deficiency has been demonstrated to impair normal functions of the immune system in animals and humans, which can be corrected by vitamin E repletion. Although deficiency is rare, vitamin E supplementation above current dietary recommendations has been shown to enhance the function of the immune system and reduce risk of infection, particularly in older individuals. The mechanisms responsible for the effect of vitamin E on the immune system and inflammation have been explored in cell‐based, pre‐clinical and clinical intervention studies. Vitamin E modulates T cell function through directly impacting T cell membrane integrity, signal transduction, and cell division, and also indirectly by affecting inflammatory mediators generated from other immune cells. Modulation of immune function by vitamin E has clinical relevance as it affects host susceptibility to infectious diseases such as respiratory infections, in addition to allergic diseases such as asthma. Studies examining the role of vitamin E in the immune system have typically focused on α‐tocopherol; however, emerging evidence suggests that other forms of vitamin E, including other tocopherols as well as tocotrienols, may also have potent immunomodulatory functions. Future research should continue to identify and confirm the optimal doses for individuals at different life stage, health condition, nutritional status, and genetic heterogeneity. Future research should also characterize the effects of non‐α‐alpha‐tocopherol vitamin E on immune cell function as well as their potential clinical application. © 2018 IUBMB Life, 71(4):487–494, 2019

Immune Impairment Associated with Vitamin A Deficiency: Insights from Clinical Studies and Animal Model Research

Type of study: literature review

Number of citations: 49

Year: 2022

Authors: J. Amimo, H. Michael, Juliet Chepngeno, Sergei A. Raev, L. Saif, A. Vlasova

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Vitamin A deficiency impairs immune response, predisposes to infections, and disrupts gut microbiome, affecting vaccine efficacy and immunization programs.

Abstract: Vitamin A (VA) is critical for many biological processes, including embryonic development, hormone production and function, the maintenance and modulation of immunity, and the homeostasis of epithelium and mucosa. Specifically, VA affects cell integrity, cytokine production, innate immune cell activation, antigen presentation, and lymphocyte trafficking to mucosal surfaces. VA also has been reported to influence the gut microbiota composition and diversity. Consequently, VA deficiency (VAD) results in the imbalanced production of inflammatory and immunomodulatory cytokines, intestinal inflammation, weakened mucosal barrier functions, reduced reactive oxygen species (ROS) and disruption of the gut microbiome. Although VAD is primarily known to cause xerophthalmia, its role in the impairment of anti-infectious defense mechanisms is less defined. Infectious diseases lead to temporary anorexia and lower dietary intake; furthermore, they adversely affect VA status by interfering with VA absorption, utilization and excretion. Thus, there is a tri-directional relationship between VAD, immune response and infections, as VAD affects immune response and predisposes the host to infection, and infection decreases the intestinal absorption of the VA, thereby contributing to secondary VAD development. This has been demonstrated using nutritional and clinical studies, radiotracer studies and knockout animal models. An in-depth understanding of the relationship between VAD, immune response, gut microbiota and infections is critical for optimizing vaccine efficacy and the development of effective immunization programs for countries with high prevalence of VAD. Therefore, in this review, we have comprehensively summarized the existing knowledge regarding VAD impacts on immune responses to infections and post vaccination. We have detailed pathological conditions associated with clinical and subclinical VAD, gut microbiome adaptation to VAD and VAD effects on the immune responses to infection and vaccines.

Vitamin D’s Effect on Immune Function

Type of study:

Number of citations: 297

Year: 2020

Authors: P. Martens, C. Gysemans, A. Verstuyf, C. Mathieu

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Vitamin D deficiency is linked to adverse outcomes, emphasizing the importance of avoiding it, especially in early life.

Abstract: Ever since its discovery by Windhaus, the importance of the active metabolite of vitamin D (1,25-dihydroxyvitamin D3; 1,25-(OH)2D3) has been ever expanding. In this review, the attention is shifted towards the importance of the extra-skeletal effects of vitamin D, with special emphasis on the immune system. The first hint of the significant role of vitamin D on the immune system was made by the discovery of the presence of the vitamin D receptor on almost all cells of the immune system. In vitro, the overwhelming effect of supra-physiological doses of vitamin D on the individual components of the immune system is very clear. Despite these promising pre-clinical results, the translation of the in vitro observations to solid clinical effects has mostly failed. Nevertheless, the evidence of a link between vitamin D deficiency and adverse outcomes is overwhelming and clearly points towards avoidance of vitamin D deficiency especially in early life.

Trace Elements as Immunoregulators in SARS-CoV-2 and Other Viral Infections

Type of study: systematic review

Number of citations: 43

Year: 2021

Authors: K. Dharmalingam, A. Birdi, S. Tomo, K. Sreenivasulu, J. Charan, Dharmveer Yadav, P. Purohit, Praveen Sharma

Journal: Indian Journal of Clinical Biochemistry

Journal ranking: Q3

Key takeaways: Trace elements, such as zinc, selenium, and iron, play a crucial role in triggering immune responses and modifying viral genomes in viral infections like COVID-19.

Abstract: Nutritional deficiency is associated with impaired immunity and increased susceptibility to infections. The complex interactions of trace elements with the macromolecules trigger the effective immune response against the viral diseases. The outcome of various viral infections along with susceptibility is affected by trace elements such as zinc, selenium, iron, copper, etc. due to their immuno-modulatory effects. Available electronic databases have been comprehensively searched for articles published with full text available and with the key words 'Trace elements', 'COVID-19', 'Viral Infections' and 'Immune Response' (i.e. separately Zn, Se, Fe, Cu, Mn, Mo, Cr, Li, Ni, Co) appearing in the title and abstract. On the basis of available articles we have explored the role of trace elements in viral infections with special reference to COVID-19 and their interactions with the immune system. Zinc, selenium and other trace elements are vital to triggerTH1 cells and cytokine-mediated immune response for substantial production of proinflammatory cytokines. The antiviral activity of some trace elements is attributed to their inhibitory effect on viral entry, replication and other downstream processes. Trace elements having antioxidants activity not only regulate host immune responses, but also modify the viral genome. Adequate dietary intake of trace elements is essential for activation, development, differentiation and numerous functions.

Nutrients Interaction with the Immune System.

Type of study: systematic review

Number of citations: 18

Year: 2021

Authors: S. Noor, S. Piscopo, Amin Gasmi

Journal: Archives of Razi Institute

Journal ranking: Q2

Key takeaways: All components of our daily diet, including vitamins, trace elements, amino acids, and fatty acids, play crucial roles in immune system development and understanding their interactions is crucial for future immune therapies and drug development.

Abstract: This study described the interactions of different nutritional components with the immune system. A detailed search was carried out on Google Scholar and PubMed databases to find out the relevant research studies using different keywords, such as 'Nutrients', 'Micronutrients', and 'Immune system and micronutrients'. Only those papers that discussed the interactions between nutrients and the components of the immune system were included in the study. This research outlined the impact of different vitamins, trace elements or metals, amino acids, and fatty acids on different immune system components. It was found that vitamins, such as vitamin A, D, and C, tend to help immune cell differentiation and enhance the expression of different cytokines. Vitamins also contribute to the proliferation of T and B cells and impact the production of white blood cells. Similarly, trace elements or metals act as enzyme cofactors and control different immune response cycles by controlling the expression of cytokines, chemokines, and other signaling molecules. Moreover, different essential and non-essential amino acids play important roles in immune system development as they are primarily involved in protein synthesis. Amino acids, such as arginine, glutamine, and alanine, modulate the expression of cytokines and also control the migration and transmigration capabilities of macrophages. They also enhance the phagocytic properties of macrophages and neutrophils. In a similar way, fatty acids act as anti-inflammatory agents since they can decrease the expression of major histocompatibility complex class I (MHC-I) and MHC-II. Furthermore, they inhibit the secretion of different inflammatory cytokines. In conclusion, all the components of our daily diet are associated with the development of the immune system, and understanding their interactions is important for future immune therapies and drug development.

Metabolism of Dietary and Microbial Vitamin B Family in the Regulation of Host Immunity

Type of study:

Number of citations: 416

Year: 2019

Authors: K. Yoshii, Koji Hosomi, Kento Sawane, J. Kunisawa

Journal: Frontiers in Nutrition

Journal ranking: Q1

Key takeaways: Intestinal microbiota composition and function significantly affect host B vitamin usage and host immunity, as they play a crucial role in regulating immune responses.

Abstract: Vitamins are micronutrients that have physiological effects on various biological responses, including host immunity. Therefore, vitamin deficiency leads to increased risk of developing infectious, allergic, and inflammatory diseases. Since B vitamins are synthesized by plants, yeasts, and bacteria, but not by mammals, mammals must acquire B vitamins from dietary or microbial sources, such as the intestinal microbiota. Similarly, some intestinal bacteria are unable to synthesize B vitamins and must acquire them from the host diet or from other intestinal bacteria for their growth and survival. This suggests that the composition and function of the intestinal microbiota may affect host B vitamin usage and, by extension, host immunity. Here, we review the immunological functions of B vitamins and their metabolism by intestinal bacteria with respect to the control of host immunity.

Nutrition, immune response, and outcome.

Type of study:

Number of citations: 112

Year: 1986

Authors: S. Chandra, R. Chandra

Journal: Progress in food & nutrition science

Journal ranking: brak

Key takeaways: Nutritional deficiencies and excesses can negatively impact immune function, with trace elements playing a crucial role in maintaining immune function and preventing secondary immunodeficiency.

Abstract: The immune system plays a key role in the body's ability to fight infection and reduce the risk of developing tumors, autoimmune and degenerative disease. Nutritional deficiencies and excesses influence various components of the immune system. Early studies investigating the association between nutrition and immunity focused on generalized protein-energy malnutrition, particularly in children in developing countries. The extent of immunological impairment depends not only on the severity of malnutrition but on the presence of infection and on the age of onset of nutritional deprivation, among other factors. In industrialized nations, immune function has been shown to be compromised in many malnourished hospitalized patients, small-for-gestational age infants, and the elderly. Obesity also may adversely influence immune function. Imbalances of single nutrients are relatively uncommon in humans, and investigations of protein and amino acids and specific vitamins, minerals, and trace elements generally are carried out in experimental animals. Deficiencies of protein and some amino acids, as well as vitamins A, E, B6 and folate, are associated with reduced immunocompetence. In contrast, excessive intake of fat, in particular polyunsaturated fatty acids (e.g. linoleic and arachidonic acids), iron, and vitamin E are immunosuppressive. Trace elements modulate immune responses through their critical role in enzyme activity. Both deficiency and excess of trace elements have been recognized. Although dietary requirements of most of these elements are met by a balanced diet, there are certain population groups and specific disease states which are likely to be associated with deficiency of one or more of these essential elements. The role of trace elements in maintenance of immune function and their causal role in secondary immunodeficiency is increasingly being recognized. There is growing research concerning the role of zinc, copper, selenium, and other elements in immunity and the mechanisms that underlie such roles. The problem of interaction of trace elements and immunity is a complex one because of the frequently associated other nutritional deficiencies, the presence of clinical or subclinical infections which in themselves have a significant effect on immunity, and finally the altered metabolism due to the underlying disease. There are many practical applications of our recently acquired knowledge regarding nutritional regulation of immunity.(ABSTRACT TRUNCATED AT 400 WORDS)

Nutrition, immunity and COVID-19

Type of study:

Number of citations: 409

Year: 2020

Authors: P. Calder

Journal: BMJ Nutrition, Prevention & Health

Journal ranking: Q1

Key takeaways: Consuming sufficient amounts of essential nutrients, particularly zinc and selenium, can support the immune system and help prevent infections.

Abstract: The immune system protects the host from pathogenic organisms (bacteria, viruses, fungi, parasites). To deal with this array of threats, the immune system has evolved to include a myriad of specialised cell types, communicating molecules and functional responses. The immune system is always active, carrying out surveillance, but its activity is enhanced if an individual becomes infected. This heightened activity is accompanied by an increased rate of metabolism, requiring energy sources, substrates for biosynthesis and regulatory molecules, which are all ultimately derived from the diet. A number of vitamins (A, B6, B12, folate, C, D and E) and trace elements (zinc, copper, selenium, iron) have been demonstrated to have key roles in supporting the human immune system and reducing risk of infections. Other essential nutrients including other vitamins and trace elements, amino acids and fatty acids are also important. Each of the nutrients named above has roles in supporting antibacterial and antiviral defence, but zinc and selenium seem to be particularly important for the latter. It would seem prudent for individuals to consume sufficient amounts of essential nutrients to support their immune system to help them deal with pathogens should they become infected. The gut microbiota plays a role in educating and regulating the immune system. Gut dysbiosis is a feature of disease including many infectious diseases and has been described in COVID-19. Dietary approaches to achieve a healthy microbiota can also benefit the immune system. Severe infection of the respiratory epithelium can lead to acute respiratory distress syndrome (ARDS), characterised by excessive and damaging host inflammation, termed a cytokine storm. This is seen in cases of severe COVID-19. There is evidence from ARDS in other settings that the cytokine storm can be controlled by n-3 fatty acids, possibly through their metabolism to specialised pro-resolving mediators.

Oxidative Stress, Antioxidant Defenses, COVID-19 and Pollution

Type of study: systematic review

Number of citations: 3

Year: 2020

Authors: S. Rivas-Arancibia, Jennifer Balderas-Miranda, Lizbeth Belmont-Zúñiga, Martín Martínez-Jáquez, E. Hernández-Orozco, Vanessa Cornejo-Trejo, Citlali Reséndiz-Ramos, Iván Cruz-García, Isaac Espinosa-Caleti, Marlen Valdés-Fuentes, E. Martinez

Journal: Medical research archives

Journal ranking: brak

Key takeaways: Chronic oxidative stress and low levels of antioxidants in degenerative diseases patients can make them more vulnerable to COVID-19, suggesting restoring essential vitamins and trace elements may help counteract immune system responses.

Abstract: Patients with degenerative diseases present a chronic oxidative stress state, which puts them at a disadvantage when facing viral infections such as COVID-19. This is because there is a close relationship between redox signaling and this inflammatory response. Therefore, chronic changes in the redox balance cause alterations in the regulation of the immune system. An inflammatory response that must be reparative and self-limited loses its function and remains over time. In a chronic state of oxidative stress, there is a deficiency of antioxidants. This results in low levels of hormones, vitamins and trace elements, which are essential for the regulation of these systems. Furthermore, low levels of antioxidants imply a diminished capacity for a regulated inflammatory responses are much more vulnerable to a cytokine storm that mainly attacks the lungs, since they present a vicious circle between the null or diminished response of the antioxidant systems and the loss of regulation of the inflammatory process. Therefore, these patients are at a disadvantage in counteracting the response of defense systems to infection from SAR-COV19. A plausible option may be to restore the levels of Vitamins A, B, C, D, E and of essential trace elements such as manganese, selenium, zinc, in the body, which are key to either preventing or reducing the severity of the response of the immune system to the disease caused by SAR-CoV2. For the present review, we searched the specific sites of the Cochrane library database, PubMed and Medscape. The inclusion criteria were documents written in English or Spanish, published during the last 10 years.

Immunomodulatory diet in pediatric age.

Type of study:

Number of citations: 3

Year: 2021

Authors: E. Verduci, E. D’Auria, A. Bosetti, E. Di Profio, S. Vizzuso, C. Milanta, Erica Pendezza, Barbara Borsani, G. Zuccotti

Journal: Minerva pediatrics

Journal ranking: Q3

Key takeaways: A balanced diet rich in DHA, arginine, vitamins, and trace elements can help prevent and counteract infections, while avoiding inflammatory conditions and promoting immune maturation and response to inflammation.

Abstract: In the last few decades, the importance of a functioning immune system and health status has become more evident. Multiple factors are able to influence the development of chronic diseases and diet is one of the most important environmental factors. Evidence demonstrates that dietary patterns high in fat and low in fiber are associated with the development of non-communicable diseases. Moreover, optimal nutritional status can modulate immune maturation and response to inflammation. During inflammatory conditions, nutritional deficiencies may occur, establishing a vicious circle, consequently a balanced nutritional status is essential to prevent and counteract infections. Dietary diversity can prevent allergic diseases and nutrients such as DHA, arginine, vitamins and trace elements have an impact on physical barriers (such as gut mucosal barrier and skin), on the immune system response and on microbiome modulation. Protein deficiencies can compromise innate and adaptive immune functions; arginine availability can affect the immune response in injured states and other disease processes; EPA and DHA can modulate both innate and adaptive immunity; prebiotics have a beneficial effect on the functioning of the immune system. Zinc, copper, selenium and iron are involved in the correct development and function of the immune system. Vitamins D, E, A, B and C have a role on immune system through different mechanisms of action. Since a complex interplay exists between diet, microbiome and epigenetic factors which determine nutrient-induced changes on the immune function, the effect of each single nutrient may be difficult to study. Well-designed intervention studies, investigating the effects of whole dietary pattern, should be performed to clarify impact of foods on the immune function and disease risk.

Vitamin D Regulation of Immune Function

Type of study: literature review

Number of citations: 64

Year: 2022

Authors: D. Bikle

Journal: Current Osteoporosis Reports

Journal ranking: Q1

Key takeaways: Vitamin D deficiency can increase the risk of SARS-CoV2 infection, and supplementing early in the course of the infection can promote an effective immune response.

Abstract: Abstract Purpose of Review To review the mechanisms by which vitamin D and its metabolites regulate the immune system to facilitate the ability of the body to prevent and/or treat SARS-CoV2 and other respiratory infections and encourage further research into the role that vitamin D supplementation plays in preventing/treating such infections. Recent Findings Vitamin D deficiency is associated with an increased risk of SARS-CoV2 and other respiratory infections. Clinical trials in general demonstrate that correction of vitamin D deficiency reduces the risk of hospitalization, ICU admission, and death from SARS-CoV2 infection. The airway epithelium and alveolar macrophages express the enzyme, CYP27B1, that produces the active metabolite of vitamin D, 1,25(OH) 2 D, and the vitamin D receptor, VDR. Vitamin D and its metabolites promote the innate immune response, which provides the first line of defense against viral and bacterial infections while restricting the adaptive immune response, which if unchecked promotes the inflammatory response leading to the acute respiratory distress syndrome and death. Summary The rationale for treating vitamin D deficiency to reduce the risk of SARS-CoV2 infection and supplementing patients with vitamin D early in the course of SARS-CoV2 infection rests primarily on the ability of vitamin D metabolites to promote an effective immune response to the infection.

Synergistic role of food and mood in shaping the immune system.

Type of study: non-rct observational study

Number of citations: 0

Year: 2020

Authors: S. Agrawal

Journal:

Journal ranking: brak

Key takeaways: A balanced diet rich in essential nutrients and antioxidants, along with a positive mood, can enhance the immune system's ability to respond and resolve infectious insults.

Abstract: A healthy outside starts from the inside”. Nutrition is intricately linked to immunity and to the risk and severity of infections. Poorly nourished individuals are at a greater risk of various bacterial, viral, and other infections. Conversely, chronic or severe infections lead to nutritional disorders or worsen the nutritional status of affected people. Balanced nutrition, especially in terms of essential nutrients, dietary intake along with environmental exposures, and nutrigenomic influences play a substantial role in the ability of the immune system to respond and resolve infectious insults.The nutriments which support and stimulate the immune system are called “Immuno-nutritional elements”that can be consumed naturally in daily food habits or, those genetically modified, or enriched nutriments.Insufficient intake of nutrients occurs in people with eating disorders, in smokers (active and passive), in individuals with chronic alcohol abuse, in certain diseases, during pregnancy and lactation, and in the elderly. Nutrient deficiency suppresses immunity by affecting innate, T-cell mediated and adaptive antibody responses, leading to dysregulation of the balanced host response. Nutrition contribute to the body’s natural defences on three levels by supporting physical barriers (skin/mucosa), cellular immunity and antibody production. Vitamins A, C, E and the trace element zinc assist in enhancing the skin barrier function. The vitamins A, B6,B12, C, D, E and folic acid and the trace elements iron, zinc, copper and selenium work in synergy to support the protective activities of the immune cells. Finally, all these micronutrients, protein with the exception of vitamin C and iron, are essential for antibody production. Correspondingly, effects of food on mood have also been observed long back, ranging from increases in happiness, contentment and alertness to feelings of depression, anxiety, failure and guilt. Significant relationship was found between more positive mood and higher fruit

The immune system and the impact of zinc during aging

Type of study:

Number of citations: 314

Year: 2009

Authors: H. Haase, L. Rink

Journal: Immunity & Ageing : I & A

Journal ranking: Q1

Key takeaways: Oral zinc supplementation can improve immunity and reduce chronic inflammation in the elderly, potentially contributing to immunosenescence.

Abstract: The trace element zinc is essential for the immune system, and zinc deficiency affects multiple aspects of innate and adaptive immunity. There are remarkable parallels in the immunological changes during aging and zinc deficiency, including a reduction in the activity of the thymus and thymic hormones, a shift of the T helper cell balance toward T helper type 2 cells, decreased response to vaccination, and impaired functions of innate immune cells. Many studies confirm a decline of zinc levels with age. Most of these studies do not classify the majority of elderly as zinc deficient, but even marginal zinc deprivation can affect immune function. Consequently, oral zinc supplementation demonstrates the potential to improve immunity and efficiently downregulates chronic inflammatory responses in the elderly. These data indicate that a wide prevalence of marginal zinc deficiency in elderly people may contribute to immunosenescence.

Malnutrition in Obesity: Is It Possible?

Type of study: literature review

Number of citations: 95

Year: 2021

Authors: Milena Kobylińska, K. Antosik, Agnieszka Decyk, K. Kurowska

Journal: Obesity Facts

Journal ranking: Q1

Key takeaways: Obesity is associated with micronutrient deficiency, which can negatively impact daily performance, intellectual and emotional state, and physical state, and may contribute to further weight gain or metabolic diseases.

Abstract: Background: The World Health Organization (WHO) classifies malnutrition as the biggest threat to public health worldwide, and this condition is observed in 20–60% of hospitalized patients. Malnutrition is a state of the body in which due to insufficient supply or incorrect absorption of essential nutrients, the body composition changes and the body’s functions are impaired. Malnutrition is associated not only with reduced body mass index but also with obesity. Summary: Obesity is defined as a paradoxical state of malnutrition, which despite excessive energy consumption is associated with a shortage of individual microelements. Deficiency or lack of homeostasis of essential micronutrients can significantly affect daily performance, intellectual and emotional state, but also the physical state of the body. Food deficiency can also contribute to further weight gain or the development of other metabolic diseases. Micronutrient deficiency may include not only incorrect dietary choices and insufficient access to nutrient-rich foods but also changes in the absorption, distribution or excretion of nutrients, and altered micronutrient metabolism resulting from systemic inflammation caused by obesity. An effective therapy method recommended for people with morbid obesity is bariatric surgery aimed at both weight loss and improving quality of life. Unfortunately, the effects of these treatments are often medium- and long-term complications associated with micronutrient deficiency as a result of reduced consumption or absorption. Therefore, the use of bariatric surgery in patients with extreme obesity can affect the metabolism of microelements and increase the risk of nutritional deficiencies. Key Messages: Studies by many authors indicate a higher incidence of food deficiency among people with excessive body weight, than in people with normal body weight of the same age and same sex. Monitoring the concentration of minerals and vitamins in blood serum is a good practice in the treatment of obesity. The proper nutritional status of the body affects not only the state of health but also the effectiveness of therapy. The aim of the review was to present the issue of malnutrition in the context of obesity.

The diabetogenic effects of chronic supplementation of vitamin C or E in rats: Interplay between liver and adipose tissues transcriptional machinery of lipid metabolism.

Type of study: non-rct experimental

Number of citations: 3

Year: 2022

Authors: Mennatallah A. Ali, R. El-Tahan, M. Kamel, Noura A. Matar, Shimaa A. Mahmoud

Journal: Life sciences

Journal ranking: Q1

Key takeaways: Chronic supplementation with vitamin C or E can negatively impact lipid metabolism and glucose homeostasis in rats, emphasizing the need for strict medical monitoring.

Role of vitamins in the metabolic syndrome and cardiovascular disease

Type of study: literature review

Number of citations: 15

Year: 2021

Authors: Asdrúbal Aguilera-Méndez, Daniel Boone-Villa, R. Nieto-Aguilar, Santiago Villafaña-Rauda, A. S. Molina, Janeth Margarita Ventura Sobrevilla

Journal: Pflügers Archiv - European Journal of Physiology

Journal ranking: Q1

Key takeaways: Vitamin supplementation may play a role in preventing and treating metabolic syndrome and cardiovascular disease, but its effectiveness remains controversial due to varying deficiency and overdose issues.

Abstract: The prevalence of metabolic syndrome and cardiovascular disease has increased and continues to be the leading cause of mortality worldwide. The etiology of these diseases includes a complex phenotype derived from interactions between genetic, environmental, and nutritional factors. In this regard, it is common to observe vitamin deficiencies in the general population and even more in patients with cardiometabolic diseases due to different factors. Vitamins are essential micronutrients for cellular metabolism and their deficiencies result in diseases. In addition to its role in nutritional functions, increasingly, vitamins are being recognized as modulators of genetics expression and signals transduction, when consumed at pharmacological concentrations. Numerous randomized preclinical and clinical trials have evaluated the use of vitamin supplementation in the prevention and treatment of metabolic syndrome and cardiovascular disease. However, it is controversy regarding its efficacy in the treatment and prevention of these diseases. In this review, we investigated chemical basics, physiological effect and recommended daily intake, problems with deficiency and overdose, preclinical and clinical studies, and mechanisms of action of vitamin supplementation in the treatment and prevention of metabolic syndrome and cardiovascular disease.

Metabolic Characteristics of Hashimoto’s Thyroiditis Patients and the Role of Microelements and Diet in the Disease Management—An Overview

Type of study: systematic review

Number of citations: 79

Year: 2022

Authors: A. Mikulska, Marta Karaźniewicz-Łada, D. Filipowicz, M. Ruchała, F. Główka

Journal: International Journal of Molecular Sciences

Journal ranking: Q1

Key takeaways: Micronutrient supplementation and a vitamin D and selenium-rich diet may improve thyroid function, maintain proper weight, and prevent nutritional deficiencies and metabolic disorders in Hashimoto's thyroiditis patients.

Abstract: Hashimoto’s thyroiditis (HT) is the most common autoimmune disease and the leading cause of hypothyroidism, in which damage to the thyroid gland occurs due to the infiltration of lymphocytes. It is characterized by increased levels of antibodies against thyroid peroxidase and thyroglobulin. In this review, we present the metabolic profile, the effectiveness of micronutrient supplementation and the impact of dietary management in patients with HT. For this current literature review, the databases PubMed, Cochrane, Medline and Embase were reviewed from the last ten years until March 2022. This article provides a comprehensive overview of recent randomized controlled trials, meta-analyses, and clinical trials. Many patients with HT, even in the euthyroid state, have excess body weight, metabolic disorders, and reduced quality of life. Due to frequent concomitant nutritional deficiencies, the role of vitamin D, iodine, selenium, magnesium, iron and vitamin B12 is currently debated. Several studies have underlined the benefits of vitamin D and selenium supplementation. There is still no specific diet recommended for patients with HT, but a protective effect of an anti-inflammatory diet rich in vitamins and minerals and low in animal foods has been suggested. There is insufficient evidence to support a gluten-free diet for all HT patients. Pharmacotherapy, along with appropriate nutrition and supplementation, are important elements of medical care for patients with HT. The abovementioned factors may decrease autoantibody levels, improve thyroid function, slow down the inflammatory process, maintain proper body weight, relieve symptoms, and prevent nutritional deficiencies and the development of metabolic disorders in patients with HT.

Biological Importance of Microelements in the Human Body

Type of study: literature review

Number of citations: 1

Year: 2024

Authors: S. Tangatarova, A. Zhumaeva, Z. Abdullaeva

Journal: Bulletin of Science and Practice

Journal ranking: brak

Key takeaways: Microelements are crucial for human metabolism, protein synthesis, heat exchange, and immune reactions, and their deficiency can lead to serious diseases.

Abstract: The human body essentially needs chemical elements for various biochemical processes and metabolic reactions. Microelements are also essential in the human body to perform essential functions in the human body. Research objectives: to study the biological significance of microelements in the human body that are part of the structure of biologically active substances: enzymes, hormones and vitamins. A literature review was carried out on the importance of microelements in the human body, examples of diseases that occur with a deficiency and excess of microelements in the body are given. A lack of microelements leads to serious diseases of the body as they are involved in the metabolism of proteins, fats, carbohydrates, protein synthesis in the body, heat exchange, hematopoiesis, bone formation, reproduction, and immune reactions. When consuming refined foods, the lack of microelements and vitamins can be eliminated by taking multivitamin-mineral complexes.

The Role of Vitamin D in Reducing the Risk of Metabolic Disturbances That Cause Cardiovascular Diseases

Type of study:

Number of citations: 16

Year: 2023

Authors: Z. Al-Oanzi, F. Alenazy, Hassan H. Alhassan, Yasir Alruwaili, Abdulaziz I. Alessa, Nouf B. Alfarm, Maha O. Alanazi, Sarah I. Alghofaili

Journal: Journal of Cardiovascular Development and Disease

Journal ranking: Q1

Key takeaways: Vitamin D deficiency increases the risk of metabolic disturbances, including obesity, diabetes, and cardiovascular disease, by lowering insulin sensitivity and affecting the body's lipid profile.

Abstract: Among the most common problems facing public health today is a lack of vitamin D, which plays a role in the physiological processes of chronic illness conditions. Vitamin D deficiency in metabolic disorders has primary effects on osteoporosis, obesity, hypertension, diabetes, and cardiovascular disease (CVD). Vitamin D acts as a “co-hormone” in the various tissues of the body, and it has been found that vitamin D receptors (VDR) are present on all cell types, suggesting that vitamin D has a wide range of effects on most cells. Recently, there has been a surge in interest in assessing its roles. Vitamin D insufficiency increases the risk of diabetes because it lowers insulin sensitivity, and also raises the risk of obesity and CVD because of its effect on the body’s lipid profile, particularly in terms of the prevalence of dangerously high levels of low-density lipoproteins (LDL). Furthermore, vitamin D insufficiency is often related to CVD and connected risk factors, highlighting the need to know vitamin D’s functions in relation to metabolic syndrome and related processes. Through looking at previous studies, this paper explains why vitamin D is important, how deficiency is related to risk factors for metabolic syndrome through different mechanisms, and how deficiency affects CVD.

STUDY OF THE EFFECT OF DEFICIENCY OF MICROELEMENTS ON CARBOHYDRATE METABOLISM

Type of study: non-rct experimental

Number of citations: 0

Year: 2018

Authors: N. V. Tolmacheva, J. Tsyganova

Journal: Trace elements in medicine

Journal ranking: brak

Key takeaways: Microelement deficiency impacts carbohydrate metabolism, with pre-diabetic changes observed in disaster zone residents, confirming the hypothesis of macro- and microelement imbalance effects.

Abstract: The article describes experimental research of the impact of microelement`s deficiency on human carbohydrate metabolism.The studies were conducted in conditions of ecological-biogeochemical optimum and disaster.The level of Cu, Si, Se, Mn, Ca, Cr, Y, F, the level of leptin, the serum glucose level were evaluated in a similar diet, and the body mass index of the experiment `s participants was determined.Correlation links between individual microelements and indicators of exchange have been revealed: leptin level, fasting glycaemia.The difference was noticed in body mass between researched persons in two groups.Pre-diabetic changes in a significant number of people living in the disaster zone have been diagnosed.The hypothesis about the effect of the imbalance of macro-and microelements on the carbohydrate metabolism in the human body has been confirmed.An auxiliary method of correction of carbohydrate metabolism has been created (Edwards, Cusi, 2016).

Evaluation of the effect of iron, zinc and selenium on metabolic processes in viral diseases

Type of study:

Number of citations: 0

Year: 2024

Authors: O. Leno, K. A. Repeta, M. V. Storozhynska, YU. M. Fedevych, P. B. Pokotylo

Journal: Experimental and Clinical Physiology and Biochemistry

Journal ranking: brak

Key takeaways: Optimal balance of macro- and microelements is crucial for effective combating viral infections, with supplementation tailored to specific age-related requirements being crucial.

Abstract: The deficiency of macro- and microelements and the disturbance of their balance are widely recognized issues in healthcare, with poor nutrition exacerbating disruptions in metabolic processes at both the cellular and organismal levels. All these metabolic circumstances and disruptions in metabolic processes contribute to the development of various pathological conditions, including viral infections. Macro- and microelements play a crucial role in many metabolic processes that affect the course of infectious diseases. These processes include oxidative phosphorylation, which is altered in patients with systemic inflammation and protection against mediators, including oxidants. Microelements are necessary for direct antioxidant activity and also function as cofactors for various antioxidant enzymes. Immune function also depends on an adequate level of vitamins and microelements. It can be enhanced by restoring microelement deficiencies to recommended levels, thereby increasing resistance to infection and promoting faster recovery after infection. Balanced nutrition alone is insufficient, hence the need for the supplementation of microelements tailored to specific age-related requirements. In this article, we explore the importance of the optimal balance of individual macro- and microelements for effectively combating viral infections.

Interplay of vitamin D and metabolic syndrome: A review.

Type of study:

Number of citations: 91

Year: 2016

Authors: P. Prasad, A. Kochhar

Journal: Diabetes & metabolic syndrome

Journal ranking: Q1

Key takeaways: Vitamin D deficiency plays a key role in the pathophysiology of metabolic syndrome, affecting cardiovascular system, insulin resistance, obesity, and hypertension, with potential implications for prevention and treatment.

ESPEN micronutrient guideline.

Type of study:

Number of citations: 307

Year: 2022

Authors: M. Berger, A. Shenkin, K. Amrein, M. Augsburger, H. Biesalski, S. Bischoff, M. Casaer, Kursat Gundogan, Hanna-Liis Lepp, A. D. de Man, G. Muscogiuri, M. Pietka, L. Pironi, S. Rezzi, A. Schweinlin, C. Cuerda

Journal: Clinical nutrition

Journal ranking: Q1

Key takeaways: This guideline provides practical advice on micronutrient provision and monitoring during nutritional support for at-risk diseases, aiming to address suboptimal and deficient status of essential nutrients.

Vitamin D and Chronic Diseases

Type of study:

Number of citations: 319

Year: 2017

Authors: Hanmin Wang, Weiwen Chen, Dongqing Li, X. Yin, Xiaode Zhang, N. Olsen, S. Zheng

Journal: Aging and Disease

Journal ranking: Q1

Key takeaways: Vitamin D deficiency is linked to chronic diseases like bone metabolic disorders, tumors, cardiovascular diseases, and diabetes, and is a risk factor for neuropsychiatric disorders and autoimmune diseases.

Abstract: Vitamin D is one of the essential nutrients to sustain the human health. As a member of the steroid hormone family, it has a classic role in regulating metabolism of calcium and a non-classic role in affecting cell proliferation and differentiation. Epidemiological studies have shown that 25OHD deficiency is closely associated with common chronic diseases such as bone metabolic disorders, tumors, cardiovascular diseases, and diabetes. 25OHD deficiency is also a risk factor for neuropsychiatric disorders and autoimmune diseases. 25OHD deficiency is highly prevalent in the world. It is therefore necessary to know the adverse health effects of 25OHD deficiency, and to design interventions and early treatments for those who are likely to have low levels of 25OHD.

Vitamins and Microelement Bioavailability in Different Stages of Chronic Kidney Disease

Type of study:

Number of citations: 79

Year: 2017

Authors: M. Jankowska, B. Rutkowski, A. Dębska-Ślizień

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Better understanding of micronutrient needs in chronic kidney disease patients could impact complications like high mortality, inflammation, and oxidative stress.

Abstract: Chronic kidney disease (CKD) predisposes one to either deficiency or toxic excess of different micronutrients. The knowledge on micronutrients—specifically water-soluble vitamins and trace elements—in CKD is very limited. Consequently, current guidelines and recommendations are mostly based on expert opinions or poor-quality evidence. Abnormalities of micronutrient resources in CKD develop for several reasons. Dietary restrictions and anorexia lead to an insufficient micronutrient intake, while diuretics use and renal replacement therapy lead to their excessive losses. Absorption is unpredictable, and metabolism impaired. Better understanding of the micronutrient needs of CKD patients could have an impact on many complications linked to vitamin and trace element disorders, including high mortality, increased risk of atherosclerosis, inflammation, oxidative stress, anemia, polyneuropathy, encephalopathy, weakness and fragility, muscle cramps, bone disease, depression, or insomnia. Here, we summarize the up-to-date knowledge on micronutrient resources in different stages of CKD, and share our experience with the assessment of micronutrient status.

Vitamin A deficiency in mice alters host and gut microbial metabolism leading to altered energy homeostasis.

Type of study: non-rct observational study

Number of citations: 59

Year: 2018

Authors: Yuan Tian, Robert G. Nichols, Jingwei Cai, A. Patterson, M. Cantorna

Journal: The Journal of nutritional biochemistry

Journal ranking: Q1

Key takeaways: Vitamin A deficiency in mice leads to altered gut microbiota and host metabolism, leading to altered energy homeostasis and hyperglycemia.

Vitamin E (Alpha-Tocopherol) Metabolism and Nutrition in Chronic Kidney Disease

Type of study:

Number of citations: 52

Year: 2022

Authors: F. Galli, M. Bonomini, D. Bartolini, Linda Zatini, G. Reboldi, Giada Marcantonini, G. Gentile, V. Sirolli, N. Di Pietro

Journal: Antioxidants

Journal ranking: Q1

Key takeaways: Chronic kidney disease (CKD) is associated with vitamin E deficiency and impaired metabolism, potentially benefiting cardiovascular disease prevention and immune and hematological complications.

Abstract: Vitamin E (alpha-tocopherol) is an essential micronutrient and fat-soluble antioxidant with proposed role in protecting tissues from uncontrolled lipid peroxidation. This vitamin has also important protein function and gene modulation effects. The metabolism of vitamin E depends on hepatic binding proteins that selectively retain food alpha-tocopherol for incorporation into nascent VLDL and tissue distribution together with esterified cholesterol and triglycerides. Chronic kidney disease (CKD) is a condition of oxidative stress and increased lipid peroxidation, that are associated with alterations of alpha-tocopherol metabolism and function. Specific changes have been reported for the levels of its enzymatic metabolites, including both short-chain and long-chain metabolites, the latter being endowed with regulatory functions on enzymatic and gene expression processes important for the metabolism of lipids and xenobiotics detoxification, as well as for the control of immune and inflammatory processes. Vitamin E therapy has been investigated in CKD using both oral vitamin E protocols and vitamin E-coated hemodialyzers, showing promising results in the secondary prevention of cardiovascular disease, as well as of immune and hematological complications. These therapeutic approaches are reviewed in the present article, together with a narrative excursus on the main findings indicating CKD as a condition of relative deficiency and impaired metabolism of vitamin E.

Vitamin D, Gut Microbiota, and Cardiometabolic Diseases—A Possible Three-Way Axis

Type of study: systematic review

Number of citations: 18

Year: 2023

Authors: Ayah Sukik, Joud Alalwani, V. Ganji

Journal: International Journal of Molecular Sciences

Journal ranking: Q1

Key takeaways: Adequate vitamin D status improves gut microbiota, potentially preventing the progression of metabolic syndrome and related cardiometabolic diseases.

Abstract: Metabolic syndrome (MetSyn) is a precursor for several cardiometabolic diseases such as obesity, type-2 diabetes mellitus (T2DM), and cardiovascular diseases. Emerging evidence suggests that vitamin D deficiency links to cardiometabolic diseases through microbiota. A combination of poor vitamin D status and dysbiosis may contribute to the progression of cardiometabolic diseases. Therefore, in this review, we present the relationship among vitamin D, microbiota, and cardiometabolic diseases with a focus on MetSyn. We searched major databases for reports on vitamin D, microbiota, and MetSyn until June 2022. We reviewed 13 reports on the relation between vitamin D and MetSyn (6 randomized controlled and 7 cross-sectional studies) and 6 reports on the effect of vitamin D on the gut microbiome. Adequate vitamin D status has a beneficial effect on gut microbiota, therefore preventing the progression of MetSyn. Further, well-controlled studies are needed for a better understanding of the mechanisms of action involving vitamin D and microbiota in the pathogenesis of cardiometabolic diseases.

Micronutrient Deficiency Pre- and Post-bariatric Metabolic Surgery in Latin America: a Systematic Review

Type of study: systematic review

Number of citations: 1

Year: 2022

Authors: D. L. González-Sánchez, Brian R. Murillo-Prado, Claudia M. Zaragoza-`Calderón, Efraín Armenta-Rojas, J. Cornejo-Bravo, V. H. Andrade-Soto, Gisela Pineda-García, A. Serrano-Medina

Journal: Obesity Surgery

Journal ranking: Q1

Key takeaways: High prevalence of micronutrient deficiency exists before and after bariatric metabolic surgery in Latin America, with vitamin D being the most affected before and vitamin A after surgery.

Abstract: BackgroundPersons submitted to bariatric metabolic surgery present micronutrient deficiency before and after surgery, due to the lack of proper supplementation. The aim of this study is to establish the prevalence of micronutrient deficiency in people before and after bariatric metabolic surgery in Latin America.MethodsThis review was conducted in accordance with the 2020 PRISMA Guidelines.ResultsTwenty-seven studies and 2135 participants were included. The highest prevalence of deficiency before surgery was reported for vitamin D (74%), zinc (71%), and hemoglobin (62%); after surgery, they were vitamin A (90.6%), vitamin D (90%), and zinc (68%).ConclusionsThere is a high prevalence of micronutrient deficiency before and after bariatric metabolic surgery from Latin American persons; the micronutrients with the highest deficiency prevalence were vitamin D before and vitamin A after bariatric metabolic surgery.Graphical Abstract

A High Vitamin C Micronutrient Supplement Is Unable to Attenuate Inflammation in People with Metabolic Syndrome but May Improve Metabolic Health Indices: A Randomised Controlled Trial

Type of study: rct

Number of citations: 4

Year: 2024

Authors: E. Vlasiuk, Masuma Zawari, Rebekah Whitehead, Jonathan Williman, A. Carr

Journal: Antioxidants

Journal ranking: Q1

Key takeaways: A high vitamin C micronutrient supplement did not reduce inflammation in people with metabolic syndrome but may improve metabolic health indices.

Abstract: Chronic low-grade inflammation is a characteristic of people with metabolic syndrome and is thought to contribute to the condition progressing to the more severe type 2 diabetes and cardiovascular disease (CVD). The aim was to carry out a double-blind randomised placebo-controlled trial in people with metabolic syndrome to determine if supplementation with a micronutrient formula containing 1000 mg/d vitamin C could attenuate inflammation in people with metabolic syndrome. We recruited 72 adults aged a median of 52 years with metabolic syndrome, defined as obesity (based on waist circumference or BMI), and at least two of hyperglycaemia, raised triglycerides, lowered HDL cholesterol, hypertension, or taking medications for these conditions. A further inclusion criteria comprised C-reactive protein (CRP) concentrations ≥ 3 mg/L, i.e., high risk of CVD. The participants were randomised to daily micronutrient formula (n = 37) or matched placebo control (n = 35) for 12 weeks. The primary outcome was change in CRP concentrations and secondary outcomes included changes in vitamin C concentrations, pro-inflammatory cytokines (IL-6, TNFα), oxidative stress marker (F2isoprostanes), glycaemic indices (glucose, insulin, HbA1c), lipid markers (triglycerides, LDL and HDL cholesterol), anthropometric parameters (weight, BMI), insulin resistance and insulin sensitivity, and metabolic severity score. The participants had a low median (Q1, Q3) vitamin C status of 29 (15, 41) µmol/L and a high proportion of hypovitaminosis C (38%) and outright deficiency (19%). Following 12 weeks of micronutrient supplementation, at least 70% of the participants reached adequate vitamin C status (≥50 µmol/L), however, there was no change in CRP concentrations relative to the placebo group (Δ−0.3 [95%CI −2.7, 2.1] mg/L, p = 0.8). Similar trends were observed for IL-6, TNFα and F2isoprostanes (p > 0.05). Instead, there were small improvements in BMI, fasting glucose and HbA1c concentrations, insulin sensitivity and metabolic severity score in the micronutrient group relative to placebo (p < 0.05). Overall, 12-week micronutrient supplementation was unable to mitigate systemic inflammation in people with metabolic syndrome but may improve several metabolic health indices.

Vitamin D deficiency in early life regulates gut microbiome composition and leads to impaired glucose tolerance in adult and offspring rats.

Type of study: non-rct experimental

Number of citations: 9

Year: 2023

Authors: Jing Liu, Junyi Liu, Jingyi Zhang, Chunyan Liu, Chunbo Qu, Lixin Na

Journal: Food & function

Journal ranking: Q1

Key takeaways: Vitamin D deficiency in early life leads to impaired glucose tolerance in adult and offspring rats, partly due to changes in gut microbiota composition and metabolites.

Abstract: Vitamin D has been found to be involved in glucose metabolism in recent years. Its deficiency is very common, especially in children. Whether vitamin D deficiency in early life affects adult diabetes risk is unknown. In this study, a rat model of early life vitamin D deficiency (F1 Early-VDD) was established by depriving it of vitamin D from the 0 to the 8th week. Further, some rats were switched to normal feeding conditions and sacrificed at the 18th week. Other rats were mated randomly to generate offspring rats (F2 Early-VDD), and F2 rats were fed under normal conditions and sacrificed at the 8th week. Serum 25(OH)D3 level decreased in F1 Early-VDD at the 8th week and returned to normal at the 18th week. Serum 25(OH)D3 level in F2 Early-VDD at the 8th week was also lower than that in control rats. Impaired glucose tolerance was observed in F1 Early-VDD at the 8th week and 18th week and also in F2 Early-VDD at the 8th week. The gut microbiota composition in F1 Early-VDD at the 8th week significantly changed. Among the top ten genera with a rich difference, Desulfovibrio, Roseburia, Ruminiclostridium, Lachnoclostridium, A2, GCA-900066575, Peptococcus, Lachnospiraceae_FCS020_ group, and Bilophila increased owing to vitamin D deficiency, whereas Blautia decreased. There were 108 significantly changed metabolites in F1 Early-VDD at the 8th week, of which 63 were enriched in known metabolic pathways. Correlations between gut microbiota and metabolites were analyzed. Blautia was positively related to 2-picolinic acid, whereas Bilophila was negatively related to indoleacetic acid. Moreover, some of the changes in microbiota, metabolites, and enriched metabolic pathways still existed in F1 Early-VDD rats at the 18th week and F2 Early-VDD rats at the 8th week. In conclusion, vitamin D deficiency in early life leads to impaired glucose tolerance in adult and offspring rats. This effect may be partly achieved by regulating gut microbiota and their co-metabolites.

Micronutrients and Markers of Oxidative Stress and Inflammation Related to Cardiometabolic Health: Results from the EHES-LUX Study

Type of study: non-rct observational study

Number of citations: 11

Year: 2020

Authors: M. Ruiz-Castell, Gwenaëlle Le Coroller, J. Landrier, Djedgiga Kerkour, Bernard Weber, G. Fagherazzi, B. Appenzeller, M. Vaillant, T. Bohn

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Metabolic syndrome is linked to chronic inflammation, with CRP, adiponectin, and leptin being key determinants, while micronutrients show no significant impact except for vitamin A in women.

Abstract: Metabolic syndrome (MetS) characteristics include chronic inflammation and elevated oxidative stress. This study assessed associations between circulating concentrations of micronutrients/phytochemicals and inflammatory/oxidative stress markers with MetS and MetS components. Adults (N = 606) from the European Health Examination Survey in Luxembourg (2013–2015) were randomly selected. We performed a multivariable logistic regression model using the least absolute shrinkage and selection operator to identify MetS-associated variables. Participants with MetS had higher concentrations of C-reactive protein (CRP), 8-iso-prostaglandin F2α, leptin, insulin, and vitamins E/A, but lower concentrations of adiponectin, beta-carotene, and oxidized low-density lipoprotein. A one-unit increase in log-CRP was associated with 51% greater odds of MetS (OR = 1.51 (95% CI: 1.16, 1.98)). Adults with a one-unit increase in log-leptin were 3.1 times more likely to have MetS (3.10 (2.10, 4.72)). Women with a one-unit increase in vitamin A were associated with 3% increased odds of MetS (1.03 (1.01, 1.05)), while those with a one-unit increase in log-adiponectin were associated with 82% decreased odds (0.18 (0.07, 0.46)). Chronic inflammation best characterized adults with MetS, as CRP, adiponectin, and leptin were selected as the main MetS determinants. Micronutrients did not seem to affect MetS, except for vitamin A in women.

Role of Vitamins in Neurodegenerative Diseases: A Review.

Type of study: systematic review

Number of citations: 46

Year: 2021

Authors: R. Kumar, Lovekesh Singh, Amandeep Thakur, Shamsher Singh, B. Kumar

Journal: CNS & neurological disorders drug targets

Journal ranking: Q2

Key takeaways: Vitamin deficiencies contribute to various neurological disorders, including Alzheimer's, Parkinson's, Huntington's, and depression, by causing oxidative stress, mitochondrial dysfunction, and neurodegeneration.

Abstract: BACKGROUND Vitamins are the micronutrients required for boosting the immune system and managing any future infection. Vitamins are involved in neurogenesis, a defense mechanism working in neurons, metabolic reactions, neuronal survival, and neuronal transmission. Their deficiency leads to abnormal functions in the brain like oxidative stress, mitochondrial dysfunction, accumulation of proteins (synuclein, Aβ plaques), neurodegeneration, and excitotoxicity. METHODS In this review, we have compiled various reports collected from PubMed, Scholar Google, Research gate, and Science direct. The findings were evaluated, compiled, and represented in this manuscript. CONCLUSION The deficiency of vitamins in the body causes various neurological disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and depression. We have discussed the role of vitamins in neurological disorders and the normal human body. Depression is linked to a deficiency of vitamin-C and vitamin B. In the case of Alzheimer's disease, there is a lack of vitamin-B1, B12, and vitamin-A, which results in Aβ-plaques. Similarly, in Parkinson's disease, vitamin-D deficiency leads to a decrease in the level of dopamine, and imbalance in vitamin D leads to accumulation of synuclein. In MS, Vitamin-C and Vitamin-D deficiency causes demyelination of neurons. In Huntington's disease, vitamin- C deficiency decreases the antioxidant level, enhances oxidative stress, and disrupts the glucose cycle. Vitamin B5 deficiency in Huntington's disease disrupts the synthesis of acetylcholine and hormones in the brain.

Vitamin C deficiency alters the transcriptome of the rat brain in a glucocorticoid-dependent manner, leading to microglial activation and reduced neurogenesis.

Type of study: non-rct experimental

Number of citations: 2

Year: 2024

Authors: Shunta Goto, Natsuki Kojima, Miyu Komori, Noe Kawade, Kenzi Oshima, Daita Nadano, Nobumitsu Sasaki, Fumihiko Horio, Tsukasa Matsuda, Shinji Miyata

Journal: The Journal of nutritional biochemistry

Journal ranking: Q1

Key takeaways: Short-term vitamin C deficiency in rats leads to microglial activation and reduced neurogenesis, potentially impairing brain function and learning and memory.

Cerebral deficiency of vitamin B5 (d-pantothenic acid; pantothenate) as a potentially-reversible cause of neurodegeneration and dementia in sporadic Alzheimer's disease.

Type of study: non-rct observational study

Number of citations: 67

Year: 2020

Authors: Jingshu Xu, S. Patassini, P. Begley, Stephanie J Church, H. Waldvogel, R. Faull, R. Unwin, G. Cooper

Journal: Biochemical and biophysical research communications

Journal ranking: Q1

Key takeaways: Cerebral vitamin B5 deficiency may cause neurodegeneration and dementia in Alzheimer's disease, which may be preventable or reversible in early stages by treating with suitable oral doses of vitamin B5.

Does Vitamin C Deficiency Affect Cognitive Development and Function?

Type of study: literature review

Number of citations: 77

Year: 2014

Authors: S. N. Hansen, P. Tveden-Nyborg, J. Lykkesfeldt

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Vitamin C deficiency can negatively impact cognitive development and function in both developing and aging brains, potentially contributing to age-related cognitive decline and stroke risk.

Abstract: Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(−/−) mice and perinatal deficiency have shown to reduce hippocampal volume and neuron number and cause decreased spatial cognition in guinea pigs, suggesting that maternal vitamin C deficiency could have severe consequences for the offspring. Furthermore, vitamin C deficiency has been proposed to play a role in age-related cognitive decline and in stroke risk and severity. The present review discusses the available literature on effects of vitamin C deficiency on the developing and aging brain with particular focus on in vivo experimentation and clinical studies.

Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice.

Type of study: non-rct experimental

Number of citations: 110

Year: 2015

Authors: S. Dixit, Alexandra Bernardo, Jennifer M. Walker, J. Kennard, Grace Youngeun Kim, E. S. Kessler, F. Harrison

Journal: ACS chemical neuroscience

Journal ranking: Q1

Key takeaways: Moderate vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation, and oxidative stress, potentially accelerating Alzheimer's disease development.

Abstract: Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer's disease and normal aging is understudied. In the present study, we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer's disease by crossing APP/PSEN1(+) bigenic mice with SVCT2(+/-) heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2(+/-) mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2(+/-) and APP/PSEN1(+) mice and the combination genotype SVCT2(+/-)APP/PSEN1(+) were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2(+/-)) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2(+/-) mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2(+/-)APP/PSEN1(+) mice compared to APP/PSEN1(+) mice with normal brain vitamin C. These data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways.

Vitamin D in Synaptic Plasticity, Cognitive Function, and Neuropsychiatric Illness

Type of study:

Number of citations: 129

Year: 2019

Authors: Phoebe Mayne, T. Burne

Journal: Trends in Neurosciences

Journal ranking: Q1

Key takeaways: Vitamin D deficiency may impair cognitive function by affecting brain plasticity and perineuronal nets, potentially aiding in treating cognitive symptoms in schizophrenia and other neuropsychiatric conditions.

Vitamin C Deficiency in the Young Brain—Findings from Experimental Animal Models †

Type of study:

Number of citations: 16

Year: 2021

Authors: P. Tveden-Nyborg

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Vitamin C deficiency may negatively impact brain development, particularly during early stages, due to its importance in antioxidant and co-factor functions.

Abstract: Severe and long-term vitamin C deficiency can lead to fatal scurvy, which is fortunately considered rare today. However, a moderate state of vitamin C (vitC) deficiency (hypovitaminosis C)—defined as a plasma concentration below 23 μM—is estimated to affect up to 10% of the population in the Western world, albeit clinical hallmarks in addition to scurvy have not been linked to vitC deficiency. The brain maintains a high vitC content and uniquely high levels during deficiency, supporting vitC’s importance in the brain. Actions include both antioxidant and co-factor functions, rendering vitamin C deficiency likely to affect several targets in the brain, and it could be particularly significant during development where a high cellular metabolism and an immature antioxidant system might increase sensitivity. However, investigations of a non-scorbutic state of vitC deficiency and effects on the developing young brain are scarce. This narrative review provides a comprehensive overview of the complex mechanisms that regulate vitC homeostasis in vivo and in the brain in particular. Functions of vitC in the brain and the potential consequences of deficiency during brain development are highlighted, based primarily on findings from experimental animal models. Perspectives for future investigations of vitC are outlined.

Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients.

Type of study:

Number of citations: 566

Year: 2006

Authors: J. Bourre

Journal: The journal of nutrition, health & aging

Journal ranking: Q1

Key takeaways: Dietary nutrients, particularly vitamins B1, B6, and B12, play a crucial role in brain structure and function, with their deficiency linked to cognitive issues and dementia.

Abstract: The objective of this update is to give an overview of the effects of dietary nutrients on the structure and certain functions of the brain. As any other organ, the brain is elaborated from substances present in the diet (sometimes exclusively, for vitamins, minerals, essential amino-acids and essential fatty acids, including omega- 3 polyunsaturated fatty acids). However, for long it was not fully accepted that food can have an influence on brain structure, and thus on its function, including cognitive and intellectuals. In fact, most micronutrients (vitamins and trace-elements) have been directly evaluated in the setting of cerebral functioning. For instance, to produce energy, the use of glucose by nervous tissue implies the presence of vitamin B1; this vitamin modulates cognitive performance, especially in the elderly. Vitamin B9 preserves brain during its development and memory during ageing. Vitamin B6 is likely to benefit in treating premenstrual depression. Vitamins B6 and B12, among others, are directly involved in the synthesis of some neurotransmitters. Vitamin B12 delays the onset of signs of dementia (and blood abnormalities), provided it is administered in a precise clinical timing window, before the onset of the first symptoms. Supplementation with cobalamin improves cerebral and cognitive functions in the elderly; it frequently improves the functioning of factors related to the frontal lobe, as well as the language function of those with cognitive disorders. Adolescents who have a borderline level of vitamin B12 develop signs of cognitive changes. In the brain, the nerve endings contain the highest concentrations of vitamin C in the human body (after the suprarenal glands). Vitamin D (or certain of its analogues) could be of interest in the prevention of various aspects of neurodegenerative or neuroimmune diseases. Among the various vitamin E components (tocopherols and tocotrienols), only alpha-tocopherol is actively uptaken by the brain and is directly involved in nervous membranes protection. Even vitamin K has been involved in nervous tissue biochemistry. Iron is necessary to ensure oxygenation and to produce energy in the cerebral parenchyma (via cytochrome oxidase), and for the synthesis of neurotransmitters and myelin; iron deficiency is found in children with attention-deficit/hyperactivity disorder. Iron concentrations in the umbilical artery are critical during the development of the foetus, and in relation with the IQ in the child; infantile anaemia with its associated iron deficiency is linked to perturbation of the development of cognitive functions. Iron deficiency anaemia is common, particularly in women, and is associated, for instance, with apathy, depression and rapid fatigue when exercising. Lithium importance, at least in psychiatry, is known for a long time. Magnesium plays important roles in all the major metabolisms: in oxidation-reduction and in ionic regulation, among others. Zinc participates among others in the perception of taste. An unbalanced copper metabolism homeostasis (due to dietary deficiency) could be linked to Alzheimer disease. The iodine provided by the thyroid hormone ensures the energy metabolism of the cerebral cells; the dietary reduction of iodine during pregnancy induces severe cerebral dysfunction, actually leading to cretinism. Among many mechanisms, manganese, copper, and zinc participate in enzymatic mechanisms that protect against free radicals, toxic derivatives of oxygen. More specifically, the full genetic potential of the child for physical growth ad mental development may be compromised due to deficiency (even subclinical) of micronutrients. Children and adolescents with poor nutritional status are exposed to alterations of mental and behavioural functions that can be corrected by dietary measures, but only to certain extend. Indeed, nutrient composition and meal pattern can exert either immediate or long-term effects, beneficial or adverse. Brain diseases during aging can also be due to failure for protective mechanism, due to dietary deficiencies, for instance in anti-oxidants and nutrients (trace elements, vitamins, non essential micronutrients such as polyphenols) related with protection against free radicals. Macronutrients are presented in the accompanying paper.

Vitamin D Deficiency Does Not Affect Cognition and Neurogenesis in Adult C57Bl/6 Mice

Type of study: non-rct experimental

Number of citations: 1

Year: 2024

Authors: Mark Doumit, C. El-Mallah, Alaa El-Makkawi, Omar Obeid, Firas Kobeissy, H. Darwish, W. Abou-Kheir

Journal: Nutrients

Journal ranking: Q1

Key takeaways: Vitamin D deficiency and supplementation do not affect brain growth, neurogenesis, or cognitive processes in adult mice over a 6-week period.

Abstract: Vitamin D deficiency is a global problem. Vitamin D, the vitamin D receptor, and its enzymes are found throughout neuronal, ependymal, and glial cells in the brain and are implicated in certain processes and mechanisms in the brain. To investigate the processes affected by vitamin D deficiency in adults, we studied vitamin D deficient, control, and supplemented diets over 6 weeks in male and female C57Bl/6 mice. The effect of the vitamin D diets on proliferation in the neurogenic niches, changes in glial cells, as well as on memory, locomotion, and anxiety-like behavior, was investigated. Six weeks on a deficient diet was adequate time to reach deficiency. However, vitamin D deficiency and supplementation did not affect proliferation, neurogenesis, or astrocyte changes, and this was reflected on behavioral measures. Supplementation only affected microglia in the dentate gyrus of female mice. Indicating that vitamin D deficiency and supplementation do not affect these processes over a 6-week period.

Chronic vitamin E deficiency impairs cognitive function in adult zebrafish via dysregulation of brain lipids and energy metabolism.

Type of study: non-rct experimental

Number of citations: 42

Year: 2017

Authors: Melissa Q. McDougall, Jaewoo Choi, K. Magnusson, L. Truong, Robert L. Tanguay, M. Traber

Journal: Free radical biology & medicine

Journal ranking: Q1

Key takeaways: Chronic vitamin E deficiency impairs cognitive function in adult zebrafish, leading to neurological dysfunction through dysregulated brain lipids and energy metabolism.

Vitamin D Deficiency Induces Chronic Pain and Microglial Phenotypic Changes in Mice

Type of study: non-rct experimental

Number of citations: 31

Year: 2021

Authors: N. Alessio, C. Belardo, M. Trotta, S. Paino, S. Boccella, F. Gargano, G. Pieretti, F. Ricciardi, I. Marabese, L. Luongo, U. Galderisi, M. D'Amico, S. Maione, F. Guida

Journal: International Journal of Molecular Sciences

Journal ranking: Q1

Key takeaways: Vitamin D deficiency leads to chronic pain and microglial phenotypic changes in mice, suggesting a potential role for these cells in sensorial dysfunctions associated with hypovitaminosis D.

Abstract: The bioactive form of vitamin D, 1,25-dihydroxyvitamin D (1,25D3), exerts immunomodulatory actions resulting in neuroprotective effects potentially useful against neurodegenerative and autoimmune diseases. In fact, vitamin D deficiency status has been correlated with painful manifestations associated with different pathological conditions. In this study, we have investigated the effects of vitamin D deficiency on microglia cells, as they represent the main immune cells responsible for early defense at central nervous system (CNS), including chronic pain states. For this purpose, we have employed a model of low vitamin D intake during gestation to evaluate possible changes in primary microglia cells obtained from postnatal day(P)2-3 pups. Afterwards, pain measurement and microglia morphological analysis in the spinal cord level and in brain regions involved in the integration of pain perception were performed in the parents subjected to vitamin D restriction. In cultured microglia, we detected a reactive—activated and proliferative—phenotype associated with intracellular reactive oxygen species (ROS) generation. Oxidative stress was closely correlated with the extent of DNA damage and increased β-galactosidase (B-gal) activity. Interestingly, the incubation with 25D3 or 1,25D3 or palmitoylethanolamide, an endogenous ligand of peroxisome proliferator-activated-receptor-alpha (PPAR-α), reduced most of these effects. Morphological analysis of ex-vivo microglia obtained from vitamin-D-deficient adult mice revealed an increased number of activated microglia in the spinal cord, while in the brain microglia appeared in a dystrophic phenotype. Remarkably, activated (spinal) or dystrophic (brain) microglia were detected in a prominent manner in females. Our data indicate that vitamin D deficiency produces profound modifications in microglia, suggesting a possible role of these cells in the sensorial dysfunctions associated with hypovitaminosis D.

Vitamin D: Brain and Behavior

Type of study:

Number of citations: 75

Year: 2020

Authors: D. Eyles

Journal: JBMR Plus

Journal ranking: Q1

Key takeaways: Vitamin D plays a crucial role in brain development and shaping behavior, with evidence linking deficiency to neurodevelopmental disorders and certain degenerative conditions.

Abstract: It has been 20 years since we first proposed vitamin D as a “possible” neurosteroid.(1) Our work over the last two decades, particularly results from our cellular and animal models, has confirmed the numerous ways in which vitamin D differentiates the developing brain. As a result, vitamin D can now confidently take its place among all other steroids known to regulate brain development.(2) Others have concentrated on the possible neuroprotective functions of vitamin D in adult brains. Here these data are integrated, and possible mechanisms outlined for the various roles vitamin D appears to play in both developing and mature brains and how such actions shape behavior. There is now also good evidence linking gestational and/or neonatal vitamin D deficiency with an increased risk of neurodevelopmental disorders, such as schizophrenia and autism, and adult vitamin D deficiency with certain degenerative conditions. In this mini‐review, the focus is on what we have learned over these past 20 years regarding the genomic and nongenomic actions of vitamin D in shaping brain development, neurophysiology, and behavior in animal models. © 2020 The Author. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Altered gut microbiota and endocannabinoid system tone in vitamin D deficiency-mediated chronic pain

Type of study: non-rct experimental

Number of citations: 94

Year: 2020

Authors: F. Guida, S. Boccella, C. Belardo, M. Iannotta, F. Piscitelli, F. De Filippis, S. Paino, F. Ricciardi, D. Siniscalco, I. Marabese, L. Luongo, D. Ercolini, V. Di Marzo, S. Maione

Journal: Brain, Behavior, and Immunity

Journal ranking: Q1

Key takeaways: Vitamin D deficiency leads to altered gut bacterial composition and altered pain processing, potentially through molecular mechanisms involving the endocannabinoid and related mediator signaling systems.

Structural and Functional Brain Changes Associated with Vitamin B12 Deficiency using Magnetic Resonance Imaging: A systematic review and meta-analysis..

Type of study: meta-analysis

Number of citations: 2

Year: 2022

Authors: Ali Alghamdi

Journal: Current medical imaging

Journal ranking: Q3

Key takeaways: Vitamin B12 deficiency leads to structural and functional brain damage in all age groups, and treatment may lead to partial or complete recovery and cognitive recovery.

Abstract: AIM This review was conducted to assess the structural and functional brain changes associated with vitamin B12 deficiency in different age groups using MRI. METHODS PubMed, Embase, Medline, CINAHL, Scopus, Web of Science, and Google Scholar were searched for magnetic resonance imaging [MRI] studies that explored structural and functional brain changes associated with vitamin B12 deficiency in different age groups. The inclusion criteria were as follows: [1] the population consisted of people and not animals; [2] patients with known B12 deficiency; [3] English publications; [3] at least one of the following brain MRI techniques had been employed: VBM, DWI, DTI, fMRI, or rs-fMRI. However, case reports, systematic reviews and meta-analysis were excluded. RESULTS Twelve articles met the inclusion criteria. The results of my review show a connection between vitamin B12 deficiency and abnormal structural and functional brain changes in several brain regions. These changes were observed in different age groups ranging from a mean age of seven years to a mean age in the 70s. The results also highlight the association between brain changes and cognitive decline among affected subjects. Improvements in damaged brain regions post-vitamin B12 treatment were also studied. CONCLUSION Structural and functional brain damage was found to be associated with vitamin B12 deficiency in all age groups. Vitamin B12 treatment may lead to partial or complete structural and/or functional recovery, as well as a cognitive recovery.

Effects of Vitamin B12 and Folate Deficiency on Brain Development in Children

Type of study:

Number of citations: 367

Year: 2008

Authors: M. Black

Journal: Food and Nutrition Bulletin

Journal ranking: Q1

Key takeaways: Vitamin B12 and folate deficiency negatively impact brain development in infants, leading to disruptions in myelination and inflammation, and increasing the risk of depression in adulthood.

Abstract: Folate deficiency in the periconceptional period contributes to neural tube defects; deficits in vitamin B12 (cobalamin) have negative consequences on the developing brain during infancy; and deficits of both vitamins are associated with a greater risk of depression during adulthood. This review examines two mechanisms linking folate and vitamin B12 deficiency to abnormal behavior and development in infants: disruptions to myelination and inflammatory processes. Future investigations should focus on the relationship between the timing of deficient and marginal vitamin B12 status and outcomes such as infant growth, cognition, social development, and depressive symptoms, along with prevention of folate and vitamin B12 deficiency.

Increased stress and altered expression of histone modifying enzymes in brain are associated with aberrant behaviour in vitamin B12 deficient female mice

Type of study: rct

Number of citations: 14

Year: 2018

Authors: Shampa Ghosh, J. K. Sinha, N. Khandelwal, S. Chakravarty, Arvind Kumar, M. Raghunath

Journal: Nutritional Neuroscience

Journal ranking: Q1

Key takeaways: Chronic vitamin B12 deficiency in female mice leads to increased stress, altered brain function, and depression, with severity correlated to the level of deficiency.

Abstract: A sub-optimal nutritional environment from early life can be envisaged as a stressor that translates into mental health problems in adulthood. After considering (a) the widespread prevalence of vitamin B12 deficiency especially amongst women in developing countries and (b) the importance of vitamin B12 in normal brain function, in this study we have elucidated the behavioural correlates of chronic severe and moderate vitamin B12 deficiency in C57BL/6 mice. Female weanling mice were assigned to three dietary groups: (a) control AIN-76A diet with cellulose as dietary fibre (b) vitamin B12 restricted AIN-76A diet with pectin as dietary fibre (severe deficiency group) and (c) vitamin B12 restricted AIN-76A diet with cellulose as dietary fibre (moderate deficiency group). The mice received these diets throughout pregnancy, lactation and thereafter. Nest-building, maternal care, anxiety and depressive behaviours were evaluated. Oxidative stress, activities of antioxidant enzymes and expression of various histone modifying enzymes in brain were investigated to unravel the probable underlying mechanisms. Our data suggests that both severe and moderate vitamin B12 deficiency induced anxiety and impaired maternal care. However, only severe vitamin B12 deficiency induced depression. Oxidative stress and poor antioxidant defense underlie the deleterious effects of both severe and moderate vitamin B12 deficiency. Altered expression of histone modifying enzymes in the brain of severely deficient mice is suggestive of epigenetic reprogramming. This study suggests that chronic vitamin B12 deficiency leads to behavioural anomalies in female C57BL/6 mice and the severity of these outcomes can be correlated to the level of deficiency.

Vitamin A Deficiency Exacerbates Gut Microbiota Dysbiosis and Cognitive Deficits in Amyloid Precursor Protein/Presenilin 1 Transgenic Mice

Type of study: rct

Number of citations: 29

Year: 2021

Authors: Bo-Wen Chen, Kai-Wen Zhang, Si Chen, Chun Yang, Peng-gao Li

Journal: Frontiers in Aging Neuroscience

Journal ranking: Q2

Key takeaways: Vitamin A deficiency exacerbates cognitive impairment in Alzheimer's disease model mice, with gut microbiota playing a key mediator role in this process.

Abstract: Vitamin A deficiency (VAD) plays an essential role in the pathogenesis of Alzheimer’s disease (AD). However, the specific mechanism by which VAD aggravates cognitive impairment is still unknown. At the intersection of microbiology and neuroscience, the gut-brain axis is undoubtedly contributing to the formation and function of neurological systems, but most of the previous studies have ignored the influence of gut microbiota on the cognitive function in VAD. Therefore, we assessed the effect of VAD on AD pathology and the decline of cognitive function in AD model mice and determined the role played by the intestinal microbiota in the process. Twenty 8-week-old male C57BL/6J amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice were randomly assigned to either a vitamin A normal (VAN) or VAD diet for 45 weeks. Our results show that VAD aggravated the behavioral learning and memory deficits, reduced the retinol concentration in the liver and the serum, decreased the transcription of vitamin A (VA)-related receptors and VA-related enzymes in the cortex, increased amyloid-β peptides (Aβ40 and Aβ42) in the brain and gut, upregulate the translation of beta-site APP-cleaving enzyme 1 (BACE1) and phosphorylated Tau in the cortex, and downregulate the expression of brain-derived neurotrophic factor (BDNF) and γ-aminobutyric acid (GABA) receptors in the cortex. In addition, VAD altered the composition and functionality of the fecal microbiota as exemplified by a decreased abundance of Lactobacillus and significantly different α- and β-diversity. Of note, the functional metagenomic prediction (PICRUSt analysis) indicated that GABAergic synapse and retinol metabolism decreased remarkably after VAD intervention, which was in line with the decreased expression of GABA receptors and the decreased liver and serum retinol. In summary, the present study provided valuable facts that VAD exacerbated the morphological, histopathological, molecular biological, microbiological, and behavioral impairment in the APP/PS1 transgenic mice, and the intestinal microbiota may play a key mediator role in this mechanism.

The effect of chronic vitamin deficiency and long term very low dose exposure to 6 pesticides mixture on neurological outcomes - a Real-Life Risk Simulation approach.

Type of study: rct

Number of citations: 46

Year: 2019

Authors: A. Tsatsakis, N. V. Tyshko, A. Docea, S. I. Shestakova, Y. Sidorova, N. Petrov, Ovidiu Mircea Zlatian, M. Mach, T. Hartung, V. Tutelyan

Journal: Toxicology letters

Journal ranking: Q2

Key takeaways: Chronic vitamin deficiency and low dose exposure to a mixture of six pesticides negatively affect the central nervous system and long-term memory in rats.

‘Unpredictable chronic mild stress does not exacerbate memory impairment or altered neuronal and glial plasticity in the hippocampus of middle‐aged vitamin D deficient mice’

Type of study:

Number of citations: 3

Year: 2024

Authors: Kelli Somelar-Duracz, M. Jürgenson, J. Viil, Alexander Zharkovsky, K. Jaako

Journal: European Journal of Neuroscience

Journal ranking: Q2

Key takeaways: Long-term vitamin D deficiency impairs cognition in middle-aged mice, but does not increase behavioral response to stress, and may contribute to altered stress response mechanisms.

Abstract: Vitamin D deficiency is a worldwide health concern, especially in the elderly population. Much remains unknown about the relationship between vitamin D deficiency (VDD), stress‐induced cognitive dysfunctions and depressive‐like behaviour. In this study, 4‐month‐old male C57Bl/6J mice were fed with control or vitamin D free diet for 6 months, followed by unpredictable chronic stress (UCMS) for 8 weeks. VDD induced cognitive impairment and reduced grooming behaviour, but did not induce depressive‐like behaviour. While UCMS in vitamin D sufficient mice induced expected depressive‐like phenotype and impairments in the contextual fear memory, chronic stress did not manifest as an additional risk factor for memory impairments and depressive‐like behaviour in VDD mice. In fact, UCMS restored self‐care behaviour in VDD mice. At the histopathological level, VDD mice exhibited cell loss in the granule cell layer, reduced survival of newly generated cells, accompanied with an increased number of apoptotic cells and alterations in glial morphology in the hippocampus; however, these effects were not exacerbated by UCMS. Interestingly, UCMS reversed VDD induced loss of microglial cells. Moreover, tyrosine hydroxylase levels decreased in the striatum of VDD mice, but not in stressed VDD mice. These findings indicate that long‐term VDD in adulthood impairs cognition but does not augment behavioural response to UCMS in middle‐aged mice. While VDD caused cell loss and altered glial response in the DG of the hippocampus, these effects were not exacerbated by UCMS and could contribute to mechanisms regulating altered stress response.

Magnetic Resonance Spectroscopy in the Hippocampus of Adult APP/PS1 mice following Chronic Vitamin D deficiency

Type of study:

Number of citations: 1

Year: 2023

Authors: Dickson Wong, M. Bellyou, Alex Li, Marco A.M. Prado, O. Beauchet, Cédric Annweiler, M. Montero‐Odasso, Robert Bartha

Journal: Behavioural brain research

Journal ranking: Q2

Key takeaways: Chronic vitamin D deficiency in APP/PS1 mice leads to compensatory changes in metabolite and astrocyte levels, contributing to improved spatial memory performance.