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Adverse Effects of Excessive Zinc Intake in Infants and Children Aged 0-3 Years: A Systematic Review and Meta-Analysis.
Ceballos-Rasgado, M, Lowe, NM, Mallard, S, Clegg, A, Moran, VH, Harris, C, Montez, J, Xipsiti, M
Advances in nutrition (Bethesda, Md.). 2022;13(6):2488-2518
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The upper limit of a nutrient’s intake has been defined as the maximum intake from food, water, and supplements that is unlikely to pose risk of adverse health effects to most individuals in the general population. The aim of this study was to determine the levels of zinc intake at which adverse effects are observed in children aged 0–3 years. This study is a systematic review and meta-analysis of fifty-eight articles from fifty-five studies. Almost all studies were randomised controlled studies (n=52) and the rest were quasi-experimental studies. Results show: - that zinc supplementation had a significant adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, haemoglobin, haematocrit, and the odds of anaemia in ≥1 of the subgroups of pooled data. - a significant reduction of the lactulose:mannitol ratio. - that there weren’t significant effects of zinc supplementation on c-reactive protein, erythrocyte superoxide dismutase [antioxidant enzyme], zinc protoporphyrin [chemical compound], blood cholesterol, or iron deficiency anaemia Authors conclude that the recommended maximum zinc doses might need to be adjusted for children at risk or recovering from iron or copper deficiency. Additionally, the study’s findings may be used to undertake dose–response modelling to estimate tolerable upper intake levels of zinc in children aged 0–3 years.
Abstract
Zinc supplementation reduces morbidity, but evidence suggests that excessive intakes can have negative health consequences. Current guidelines of upper limits (ULs) of zinc intake for young children are extrapolated from adult data. This systematic review (PROSPERO; registration no. CRD42020215187) aimed to determine the levels of zinc intake at which adverse effects are observed in young children. Studies reporting potential adverse effects of zinc intake in children aged 0-3 y were identified (from inception to August 2020) in MEDLINE, Embase, and the Cochrane Library, with no limits on study design. Adverse clinical and physical effects of zinc intake were synthesized narratively, and meta-analyses of biochemical outcomes were conducted. Random effects models were used to generate forest plots to examine the evidence by age category, dose, dose duration, chemical formula of zinc, and zinc compared with placebo. The Joanna Briggs Institute Critical Appraisal Checklist, Cochrane Risk of Bias 2, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline were employed to assess risk of bias and to appraise the certainty of evidence. Fifty-eight studies assessed possible adverse effects of zinc doses ranging from 3 to 70 mg/d. Data from 39 studies contributed to meta-analyses. Zinc supplementation had an adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, hemoglobin, hematocrit, and the odds of anemia in ≥1 of the subgroups investigated. Lactulose:mannitol ratio was improved with zinc supplementation, and no significant effect was observed on C-reactive protein, erythrocyte superoxide dismutase, zinc protoporphyrin, blood cholesterol, and iron deficiency anemia. The certainty of the evidence, as assessed using GRADE, was very low to moderate. Although possible adverse effects of zinc supplementation were observed in some subgroups, it is unclear whether these findings are clinically important. The synthesized data can be used to undertake a dose-response analysis to update current guidelines of ULs of zinc intake for young children.
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Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections.
Calder, PC, Carr, AC, Gombart, AF, Eggersdorfer, M
Nutrients. 2020;12(4)
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Acute respiratory tract infections are a major cause of morbidity and mortality across the globe with seasonal influenza epidemics and outbreaks of viruses, such as Covid-19. The authors support public hygiene practices and the development of vaccinations however call for further strategies in order to reduce the impact that these infections have on societies. The role nutrition plays in supporting the immune system is well established. This review article and opinion piece presents the evidence for Vitamins A, B6, B12, C, D, E and folate; trace elements including zinc, selenium, magnesium and copper; and omega-3 fatty acids in supporting the immune system. The authors call for the consumption of a well-balanced diet, with additional supplementation of key immune supportive nutrients. Well referenced and with a helpful table of the rationale and recommended nutrient intake levels, Nutrition Practitioners will find this article useful when working to support client immune health.
Abstract
Public health practices including handwashing and vaccinations help reduce the spread and impact of infections. Nevertheless, the global burden of infection is high, and additional measures are necessary. Acute respiratory tract infections, for example, were responsible for approximately 2.38 million deaths worldwide in 2016. The role nutrition plays in supporting the immune system is well-established. A wealth of mechanistic and clinical data show that vitamins, including vitamins A, B6, B12, C, D, E, and folate; trace elements, including zinc, iron, selenium, magnesium, and copper; and the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid play important and complementary roles in supporting the immune system. Inadequate intake and status of these nutrients are widespread, leading to a decrease in resistance to infections and as a consequence an increase in disease burden. Against this background the following conclusions are made: (1) supplementation with the above micronutrients and omega-3 fatty acids is a safe, effective, and low-cost strategy to help support optimal immune function; (2) supplementation above the Recommended Dietary Allowance (RDA), but within recommended upper safety limits, for specific nutrients such as vitamins C and D is warranted; and (3) public health officials are encouraged to include nutritional strategies in their recommendations to improve public health.
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Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus.
McCarty, MF, DiNicolantonio, JJ
Progress in cardiovascular diseases. 2020;63(3):383-385
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This highly technical review paper summarises some known actions and mechanisms by which certain nutraceuticals can boost the type 1 interferon response, a specific immune response to viruses, including influenza and coronavirus. These include: Ferulate (ferulic acid) has been shown to stimulate type 1 interferon production, and enhanced survival in influenza A-infected mice. Sulforaphane (phytochemical found in cruciferous vegetables like broccoli) and lipoic acid have similar actions. Spirulina extract has been found to decrease mortality in influenza-infected mice. Clinical and preclinical evidence for the potential benefits of N-acetylcysteine (NAC), a precursor for the important antioxidant glutathione, and selenium are also discussed. A glucosamine-enriched diet increased survival of mice infected with influenza virus. The authors present a table with suggested dosages for the above nutrients, as well as yeast beta-glucans, zinc and elderberry extracts, for viral control, whilst calling for more research into these compounds.
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The Malnutritional Status of the Host as a Virulence Factor for New Coronavirus SARS-CoV-2.
Briguglio, M, Pregliasco, FE, Lombardi, G, Perazzo, P, Banfi, G
Frontiers in medicine. 2020;7:146
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This opinion article explores the role of an individual’s nutrition status when subjected to infection by viruses, in particular Covid-19. Distinction is made between the susceptibility to infection in the first instance and the ability to persist in fighting infection once it is established. For Covid-19, it is argued that a healthier nutritional status, in particular Vitamins A, B, C, D and E, iron selenium and zinc, will lower susceptibility to infection, lower the severity of the virus and therefore reduce the length of time an individual has to find reserves to fight the virus. More severe cases of Covid-19 infection also often include gastro-intestinal symptoms which further exacerbate nutritional status with lowered appetite. The authors conclude that malnourished individuals may be more susceptible to Covid-19 infection and that nutritional support is vital in severe cases. The article includes a useful diagram of both hyponutrition and hypernutrition and possible impacts of Covid-19.
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Nutrition amid the COVID-19 pandemic: a multi-level framework for action.
Naja, F, Hamadeh, R
European journal of clinical nutrition. 2020;74(8):1117-1121
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This Lebanese articled provides a commentary on the evolving COVID-19 pandemic and aims to give a framework for Nutritional action to help the physical and mental health of individuals, communities, and nations. At an individual level the focus is on the link between diet and immunity and the profound effect diet has on people’s immune system and disease susceptibility. An adequate intake of iron, zinc, and vitamins A, E, B6, and B12 is predominantly vital for the maintenance of immune function. Individuals should aim to eat as healthily as possible, including a wide range of fruits and vegetables, limit snacking, take regular exercise and get an adequate amount of sleep to support their health. Single foods promising cures or prevention of infection are unfounded claims which can give a false sense of security. The focus for communities is on food availability, for nations its food security and on a global level it is about food trade agreements. Its important to protect against hoarding and panic buying to ensure enough food for everyone. National economic instability during COVID-19 can lead to a risk of food security so governments are advised to support local agricultural produce and reduce their reliance on imported goods. Global supply chains and agreements need to be respected to lessen the impact further down the supply chain. The health of each individual has a direct impact on the community and nation and is a direct consequence of their dietary awareness and choices.
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Individual risk management strategy and potential therapeutic options for the COVID-19 pandemic.
Gasmi, A, Noor, S, Tippairote, T, Dadar, M, Menzel, A, Bjørklund, G
Clinical immunology (Orlando, Fla.). 2020;215:108409
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With the continuing spread of COVID-19 and lack of any approved treatments, this paper examines possible strategies for prevention. The data emerging so far highlights that individual health status plays a critical role in determining clinical severity of COVID-19 symptoms ranging from asymptomatic, mild, moderate, to death. Metabolic status, as determined by a patient’s diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors can therefore be considered preventative strategies to improve the severity of COVID-19 outcomes. Social distancing and personal hygiene are stated as the most effective strategies to prevent or slow spread of the disease. However individual health status, age and the presence of pre-existing comorbidities influences outcomes, as shown by global data highlighting a prevalence in older, males with metabolic conditions; hypertension in 23.7% patients and diabetes in 16.2% of patients. Older males appear more prone to infectious diseases with high pro-inflammatory immune responses and low adaptive immune responses than an older woman. Diet and healthy intestinal and respiratory tract microbiota may also influence immune system competence. Numerous micronutrients are essential for immunocompetence, particularly vitamin A, C, D, E, Bs, iron, selenium, and zinc. A balanced diet, high in colourful fruits and vegetables with a variation of prebiotic fibres, probiotics, and plant polyphenols and phytonutrients, help promote a healthy, diverse microbiota. Oral probiotics may also be beneficial to vulnerable individuals. Vitamin D supplementation is also proving helpful in prevention of acute respiratory tract infections. Other lifestyle factors such as smoking and exposure to environmental toxins should also be considered. Together these preventative measures may reduce personal risk of getting the disease.
Abstract
It is an ugly fact that a significant amount of the world's population will contract SARS-CoV-II infection with the current spreading. While a specific treatment is not yet coming soon, individual risk assessment and management strategies are crucial. The individual preventive and protective measures drive the personal risk of getting the disease. Among the virus-contracted hosts, their different metabolic status, as determined by their diet, nutrition, age, sex, medical conditions, lifestyle, and environmental factors, govern the personal fate toward different clinical severity of COVID-19, from asymptomatic, mild, moderate, to death. The careful individual assessment for the possible dietary, nutritional, medical, lifestyle, and environmental risks, together with the proper relevant risk management strategies, is the sensible way to deal with the pandemic of SARS-CoV-II.
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Low Zinc, Copper, and Manganese Intake is Associated with Depression and Anxiety Symptoms in the Japanese Working Population: Findings from the Eating Habit and Well-Being Study.
Nakamura, M, Miura, A, Nagahata, T, Shibata, Y, Okada, E, Ojima, T
Nutrients. 2019;11(4)
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Diet, as well as other lifestyle factors (sleep, exercise etc) are thought to play a significant role in the occurrence of mental disorders, including depression and anxiety. This study focused on the dietary intake of particular minerals (zinc, copper and manganese) and their effects on depression and anxiety of 2089 Japanese participants, each in full time employment. Reasons for the occurrence of mental disorders are considered multi-factorial, but insufficient mineral intake (particularly zinc) is believed to be a causal factor in the prevalence of depression and anxiety. Results of this cross-sectional study showed that low intake of zinc, copper and manganese was associated with depression and anxiety symptoms. More specifically, the effect of both low zinc and low copper intake indicated a higher susceptibility towards depression with both low and high manganese status, suggesting low zinc and copper intake contributes to depression and anxiety symptoms regardless of manganese status. Researchers acknowledge that more investigation is needed.
Abstract
Epidemiological studies have suggested that there is an association between diet and mental health. The aim of this study was to investigate the association between the intake of six minerals and mental disorders in a cross-sectional study. We used data from the Eating Habit and Well-being study in Japanese workers. Kessler's six-item psychological distress scale was used to detect mental disorders, with a cut-off score of 12/13, and a validated food frequency questionnaire was used to estimate dietary mineral intake. A total of 2089 participants with no history of depression were included. The prevalence of mental disorders was 6.9%. The lowest quartiles of zinc, copper, and manganese intakes were associated with mental disorders, whereas the lowest quartiles of calcium, magnesium, and iron intake were not associated with mental disorders. Combination analysis of high (≥median) or low (
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Nutritional strategies for psoriasis: current scientific evidence in clinical trials.
Zuccotti, E, Oliveri, M, Girometta, C, Ratto, D, Di Iorio, C, Occhinegro, A, Rossi, P
European review for medical and pharmacological sciences. 2018;22(23):8537-8551
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Psoriasis is an inflammatory skin disease that results in patches of dry, scaly skin that can be itchy or sore. This review looked at the evidence for a variety of nutritional and herbal strategies for reducing the risk and severity of psoriasis. Obesity is associated with both an increased risk of psoriasis, and increased severity of the disease, with obese patients being twice as likely to suffer from psoriasis as people of normal weight. Abdominal obesity in particular is associated with chronic low-grade inflammation that contributes to immune dysregulation. In obese patients, weight reduction via a low-calorie diet has been shown to reduce the severity of psoriasis. A Mediterranean-style diet, rich in extra virgin olive oil, fish, fruit vegetables, legumes, nuts and seeds is associated with a lower incidence of psoriasis. In contrast, a diet high in simple carbohydrates, high in arachidonic acid, and a low omega 3: omega 6 ratio is likely to drive inflammation, worsening severity of the disease. The microbiota plays a role in the development of psoriasis, with disruption of the gut and skin microbiomes both associated with psoriasis. In particular, psoriasis patients have a reduced abundance of Akkermansia muciniphilia in their gut. Several Lactobacillus strains have demonstrated potential for therapeutic effects in psoriasis patients when taken as a supplement. Common nutritional supplements used by psoriasis patients are fish oil, selenium, and zinc. In a review of the efficacy of fish oil supplementation, 12 of 15 trials showed a benefit. The evidence for zinc supplementation is less robust. There is limited data on the effectiveness of selenium supplementation, however low serum selenium levels are associated with increased psoriasis severity. Vitamin D levels are lower in psoriasis patients and correlate with disease severity. In individuals who are deficient, supplementing with vitamin D may prevent psoriasis-related comorbidities. Amongst the herbal and botanical remedies studied, neem, turmeric, Tripterygium wilfordii (Thunder God Vine), and the carotenoid-rich alga Dunaliella bardawil may reduce the severity of psoriasis. The review authors concluded that an integrated multidisciplinary approach should be considered for the management of psoriasis patients. Education to modify lifestyle and environmental risk factors is important. A collaboration between nutritionists and medical specialists with a holistic approach may be useful for psoriasis patients.
Abstract
OBJECTIVE Several nutritional strategies for the management of psoriasis are promising. Even if recent data support that nutrition may play a pivotal role in prevention and co-treatment and despite patient's concerns regarding the best nutritional habits, the consensus regarding the nutritional strategies to be adopted lacks in clinical settings. In this manuscript, the effects of several nutritional strategies for psoriasis patients such as hypocaloric diet, vitamin D, fish oil, selenium, and zinc supplementation were systematically reviewed. Randomized controlled trials (RCTs) on beneficial botanical oral supplements were also included in the analysis. MATERIALS AND METHODS For each topic, a search was conducted in MEDLINE electronic databases for articles published in English between January 1, 1990 and September 2018. Two independent reviewers assessed and extracted the data. Only controlled clinical trials were selected. RESULTS The evidence regarding the current nutritional strategies for psoriasis patients were summarized and translated into a global, comprehensible recommendation. CONCLUSIONS Weight loss combined with a healthy lifestyle was shown to be very beneficial for patients with moderate to severe disease with a significant reduction of the Psoriasis Area and Severity Index (PASI) score. Currently, oral vitamin D supplementation for prevention or treatment of psoriasis in adults with normal vitamin D levels is not recommended; however, psoriasis patients with a deficit in plasma vitamin D levels are advised to complement with oral supplements to prevent psoriasis-related comorbidities. Instead of zinc, selenium, and omega 3 supplements have been proven beneficial for psoriasis patients. Among botanical species, Dunaliella bardawil (D. bardawil), Tripterygium wilfordii (T. wilfordii), Azadirachta indica (A. indica), Curcuma longa (C. longa), and HESA-A are the most beneficial. In conclusion, a close cooperation between nutritionists and dermatologists may be useful for the management of psoriasis.
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Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage.
Hemilä, H
JRSM open. 2017;8(5):2054270417694291
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Zinc lozenges are sometimes used to reduce the symptoms of the common cold. However studies have had varying results, possibly due to using different doses, as well as different forms of zinc. The aim of this meta-analysis was to compare the efficacy of zinc acetate lozenges with zinc gluconate lozenges in reducing the duration of the common cold and to examine the dose-dependency of the effect. The study authors looked at seven randomised trials with 575 participants with common colds. All of the trials were placebo-controlled and used zinc doses of over 75 mg/day. Three of the trials used zinc lozenges composed of zinc acetate, and four used zinc gluconate. Overall, zinc lozenges reduced cold duration by 33% compared to a placebo. The trials that used lozenges composed of zinc acetate found that colds were shortened by 40% and zinc gluconate reduced duration by 28%. The difference between the two forms was not statistically significant. Five trials used zinc doses of 80–92 mg/day, and common cold duration was reduced by 33%. Two trials used zinc doses of 192–207 mg/day and found an effect of 35%. The difference was not statistically significant. The authors concluded that zinc gluconate lozenges are equally as effective as zinc acetate lozenges. There is no evidence that zinc doses over 100 mg/day are more effective in reducing the duration of the common cold.
Abstract
OBJECTIVE To compare the efficacy of zinc acetate lozenges with zinc gluconate lozenges in common cold treatment and to examine the dose-dependency of the effect. DESIGN Meta-analysis. SETTING Placebo-controlled zinc lozenge trials, in which the zinc dose was > 75 mg/day. The pooled effect of zinc lozenges on common cold duration was calculated by using inverse-variance random-effects method. PARTICIPANTS Seven randomised trials with 575 participants with naturally acquired common colds. MAIN OUTCOME MEASURE Duration of the common cold. RESULTS The mean common cold duration was 33% (95% CI 21% to 45%) shorter for the zinc groups of the seven included trials. Three trials that used lozenges composed of zinc acetate found that colds were shortened by 40% and four trials that used zinc gluconate by 28%. The difference between the two salts was not significant: 12 percentage points (95% CI: -12 to + 36). Five trials used zinc doses of 80-92 mg/day, common cold duration was reduced by 33%, and two trials used zinc doses of 192-207 mg/day and found an effect of 35%. The difference between the high-dose and low-dose zinc trials was not significant: 2 percentage points (95% CI: -29 to + 32). CONCLUSIONS Properly composed zinc gluconate lozenges may be as effective as zinc acetate lozenges. There is no evidence that zinc doses over 100 mg/day might lead to greater efficacy in the treatment of the common cold. Common cold patients may be encouraged to try zinc lozenges for treating their colds. The optimal lozenge composition and dosage scheme need to be investigated further.