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The Effects of Dairy Product and Dairy Protein Intake on Inflammation: A Systematic Review of the Literature.
Nieman, KM, Anderson, BD, Cifelli, CJ
Journal of the American College of Nutrition. 2021;40(6):571-582
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Systemic inflammation contributes to the risk and progression of chronic disease, which is in turn influenced by several factors including diet. The aim of this study was to conduct a systematic review to evaluate the effect of dairy products and dairy protein on markers of inflammation in adults that do not have inflammatory-related disorders. The authors analysed 27 previous randomised controlled trial, of which 19 looked at dairy products, and eight looked at dairy protein (casein or whey). In the trials which evaluated dairy products, 10 reported no effect of the intervention, while eight reported a reduction in at least one biomarker of inflammation. All eight trials that investigated dairy protein intake on markers of inflammation reported no effect. The researchers concluded that the available literature suggests that dairy products and dairy proteins have neutral to beneficial effects on biomarkers of inflammation. Additional clinical studies designed using inflammatory biomarkers as the primary outcome are needed to fully understand the effects of dairy intake on inflammation.
Abstract
Systemic inflammation is associated with obesity and chronic disease risk. Intake of dairy foods is associated with reduced risk of type 2 diabetes and cardiovascular disease; however, the impact of dairy foods on inflammation is not well-established. The objective of this study was to conduct a systematic review to evaluate the effect of dairy product (milk, cheese, and yogurt) and dairy protein consumption on low-grade systemic inflammation in adults without severe inflammatory disorders. A literature search was completed in September 2019 using PubMed and CENTRAL as well as inspection of reference lists from relevant review articles. The search resulted in the identification of 27 randomized controlled trials which were included in this analysis. In the 19 trials which evaluated dairy products, 10 reported no effect of the intervention, while 8 reported a reduction in at least one biomarker of inflammation. All 8 trials that investigated dairy protein intake on markers of inflammation reported no effect of the intervention. The available literature suggests that dairy products and dairy proteins have neutral to beneficial effects on biomarkers of inflammation. Additional clinical studies designed using inflammatory biomarkers as the primary outcome are needed to fully elucidate the effects of dairy intake on inflammation.
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Association of prior metabolic and bariatric surgery with severity of coronavirus disease 2019 (COVID-19) in patients with obesity.
Aminian, A, Fathalizadeh, A, Tu, C, Butsch, WS, Pantalone, KM, Griebeler, ML, Kashyap, SR, Rosenthal, RJ, Burguera, B, Nissen, SE
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2021;17(1):208-214
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A growing body of evidence indicates that patients with obesity are disproportionately affected with a severe form of SARS-CoV-2 infection and may experience resultant higher mortality. The aim of this study was to determine the association of prior metabolic surgery with severity of SARSCoV-2 infection in patients with severe obesity. This study is a retrospective, matched-cohort analysis of a prospective, observational, institutional review board–approved clinical registry of all patients tested for SARS-CoV-2 infection. The study population included a total of 363 patients, including 33 individuals who had metabolic surgery and 330 matched patients who tested positive. Results indicate that a history of metabolic surgery is associated with lower severity of SARSCoV-2 infection in patients with severe obesity, as manifested by lower risks of hospital and ICU admission. Authors conclude that prior metabolic surgery with subsequent weight loss and improvement of metabolic abnormalities could potentially reduce morbidity from SARS-CoV-2 infection.
Abstract
BACKGROUND Obesity is a risk factor for poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19). OBJECTIVES To investigate the relationship between prior metabolic surgery and the severity of COVID-19 in patients with severe obesity. SETTING Cleveland Clinic Health System in the United States. METHODS Among 4365 patients who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between March 8, 2020 and July 22, 2020 in the Cleveland Clinic Health System, 33 patients were identified who had a prior history of metabolic surgery. The surgical patients were propensity matched 1:10 to nonsurgical patients to assemble a cohort of control patients (n = 330) with a body mass index (BMI) ≥ 40 kg/m2 at the time of SARS-CoV-2 testing. The primary endpoint was the rate of hospital admission. The exploratory endpoints included admission to the intensive care unit (ICU), need for mechanical ventilation and dialysis during index hospitalization, and mortality. After propensity score matching, outcomes were compared in univariate and multivariate regression models. RESULTS The average BMI of the surgical group was 49.1 ± 8.8 kg/m2 before metabolic surgery and was down to 37.2 ± 7.1 at the time of SARS-CoV-2 testing, compared with the control group's BMI of 46.7 ± 6.4 kg/m2. In the univariate analysis, 6 (18.2%) patients in the metabolic surgery group and 139 (42.1%) patients in the control group were admitted to the hospital (P = .013). In the multivariate analysis, a prior history of metabolic surgery was associated with a lower hospital admission rate compared with control patients with obesity (odds ratio, 0.31; 95% confidence interval, 0.11-0.88; P = .028). While none of the 4 exploratory outcomes occurred in the metabolic surgery group, 43 (13.0%) patients in the control group required ICU admission (P = .021), 22 (6.7%) required mechanical ventilation, 5 (1.5%) required dialysis, and 8 (2.4%) patients died. CONCLUSION Prior metabolic surgery with subsequent weight loss and improvement of metabolic abnormalities was associated with lower rates of hospital and ICU admission in patients with obesity who became infected with SARS-CoV-2. Confirmation of these findings will require larger studies.
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Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial.
Holm Nielsen, S, Sardar, S, Siebuhr, AS, Schlemmer, A, Schmidt, EB, Bay-Jensen, AC, Karsdal, MA, Christensen, JH, Kristensen, S
Rheumatology international. 2021;41(6):1065-1077
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Psoriatic arthritis is a chronic inflammatory condition that causes joint pain and swelling along with red, flaky, and scaly skin. Inflammation affects the extracellular matrix, which comprises proteins and molecules that support cartilage, bone, and soft tissues in joints. A high level of collagen fragments is released into the bloodstream as a result. Fish oils and fish are good sources of n-3 polyunsaturated fatty acids (n-3 PUFA), including eicosapentaenoic acid and docosahexaenoic acid. Inflammation and joint pain have been shown to be reduced by n-3 PUFA in previous studies. This randomised, double-blinded, placebo-controlled study randomly assigned 142 patients with psoriatic arthritis to receive 3g n-3 PUFA (50% EPA and 50% DHA) or 3g of olive oil as the control for 24 weeks. Taking N-3 PUFA supplementation did not affect extracellular matrix turnover in psoriatic arthritis patients. This may be due to the anti-inflammatory properties of olive oil, which was used as a control, and to the short duration of the study. The benefits of using n-3 PUFA as a therapeutic strategy in patients with psoriatic arthritis need to be evaluated in larger, robust long-term studies. Furthermore, the clinical efficacy of n-3 PUFA cannot be distinguished since 75% of the patients took anti-rheumatic drugs. A study like this can provide healthcare professionals with insights into the potential benefits of n-3 PUFAs, which may aid them in making therapeutic decisions.
Abstract
Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by involvement of skin, axial and peripheral skeleton. An altered balance between extracellular matrix (ECM) formation and breakdown is a key event in PsA, and changes in ECM protein metabolites may provide insight to tissue changes. Dietary fish oils (n-3 PUFA) might affect the inflammation driven tissue turnover. The aim was to evaluate ECM metabolites in patients with PsA compared to healthy individuals and investigate the effects of n-3 PUFA. The 24-week randomized, double-blind, placebo-controlled trial of PUFA included 142 patients with PsA. Fifty-seven healthy individuals were included for comparison. This study is a sub-study investigating biomarkers of tissue remodelling as secondary outcomes. Serum samples at baseline and 24 weeks and healthy individuals were obtained, while a panel of ECM metabolites reflecting bone and soft tissue turnover were measured by ELISAs: PRO-C1, PRO-C3, PRO-C4, C1M, C3M, C4M, CTX-I and Osteocalcin (OC). C1M, PRO-C3, PRO-C4 and C4M was found to be elevated in PsA patients compared to the healthy individuals (from 56 to 792%, all p < 0.0001), where no differences were found for OC, CTX-I, PRO-C1 and C3M. PRO-C3 was increased by 7% in patients receiving n-3 PUFA after 24 weeks compared to baseline levels (p = 0.002). None of the other biomarkers was changed with n-3 PUFA treatment. This indicates that tissue turnover is increased in PsA patients compared to healthy individuals, while n-3 PUFA treatment for 24 weeks did not have an effect on tissue turnover. Trial registration NCT01818804. Registered 27 March 2013-Completed 18 February 2016. https://clinicaltrials.gov/ct2/show/NCT01818804?term=NCT01818804&rank=1.
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Fruit and vegetable consumption and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of prospective studies.
Halvorsen, RE, Elvestad, M, Molin, M, Aune, D
BMJ nutrition, prevention & health. 2021;4(2):519-531
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Type 2 diabetes is a growing health concern worldwide, with projections estimating it will affect over 700 million people by 2045. Studies have indicated a link between increased consumption of fruits and vegetables and decreased risk of Type 2 diabetes. This systematic review and meta-analysis of twenty-three prospective cohort studies explored this link further, examining the effects of different types of fruits and vegetables on the risk of Type 2 diabetes. The results suggest that a high intake of combined fruits and vegetables and specific varieties, such as apples, pears, blueberries, grapes, and raisins, may slightly reduce the risk of developing Type 2 diabetes. However, consuming cantaloupe, fruit drinks, fruit juice, potatoes, Brussels sprouts, and cabbage may increase the risk of developing Type 2 diabetes. The protective effect of fruit and vegetable consumption on the reduction of type 2 diabetes could be attributed to the dietary fibre, antioxidants, vitamins and minerals and phytochemicals present in fruits and vegetables. While further studies are necessary to confirm these results and explore the impact of specific types of fruits and vegetables on Type 2 diabetes risk, healthcare professionals can use this information to promote the protective benefits of including specific subtypes of fruits and vegetables in the diet to reduce the risk of Type 2 diabetes.
Abstract
BACKGROUND The association between intake of fruit and vegetables and their subtypes, and the risk of type 2 diabetes has been investigated in several studies, but the results have been inconsistent. OBJECTIVE We conducted an updated systematic review and dose-response meta-analysis of prospective studies on intakes of fruit and vegetables and fruit and vegetable subtypes and the risk of type 2 diabetes. DESIGN PubMed and Embase databases were searched up to 20 October 2020. Prospective cohort studies of fruit and vegetable consumption and type 2 diabetes mellitus were included. Summary relative risks (RRs) and 95% CIs were estimated using a random effects model. RESULTS We included 23 cohort studies. The summary RR for high versus low intake and per 200 g/day were 0.93 (95% CI: 0.89 to 0.98, I2=0%, n=10 studies) and 0.98 (95% CI: 0.95 to 1.01, I2=37.8%, n=7) for fruit and vegetables combined, 0.93 (95% CI: 0.90 to 0.97, I2=9.3%, n=20) and 0.96 (95% CI: 0.92 to 1.00, I2=68.4%, n=19) for fruits and 0.95 (95% CI: 0.88 to 1.02, I2=60.4%, n=17) and 0.97 (95% CI: 0.94 to 1.01, I2=39.2%, n=16) for vegetables, respectively. Inverse associations were observed for apples, apples and pears, blueberries, grapefruit and grapes and raisins, while positive associations were observed for intakes of cantaloupe, fruit drinks, fruit juice, brussels sprouts, cauliflower and potatoes, however, most of these associations were based on few studies and need further investigation in additional studies. CONCLUSIONS This meta-analysis found a weak inverse association between fruit and vegetable intake and type 2 diabetes risk. There is indication of both inverse and positive associations between intake of several fruit and vegetables subtypes and type 2 diabetes risk, however, further studies are needed before firm conclusions can be made.
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Plant-based dietary quality and depressive symptoms in Australian vegans and vegetarians: a cross-sectional study.
Lee, MF, Eather, R, Best, T
BMJ nutrition, prevention & health. 2021;4(2):479-486
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Poor diet and mood disorders are known leading causes of morbidity and mortality. Some studies suggest that plant-based diets are associated with improved mood and mental health. The aim of this study was to explore the association between vegan and vegetarian dietary patterns and depressive symptoms in adults by exploring the overall dietary quality of these patterns. This study is an online cross-sectional study which invited vegan and vegetarian adults aged between 18 and 44 years who live in Australia to complete an online survey through social media platforms. Results show that high plant-based diets quality was associated with decreased risk of depressive symptoms. However, this study also shows that following a plant-based diet does not necessarily mean the individual consumes a ‘healthy’ dietary pattern. Authors conclude that further studies are needed which should focus on the specific quality of vegan and vegetarian diets in relation to depression and mental well-being.
Abstract
Plant-based dietary patterns (vegan and vegetarian) are often considered 'healthy' and have been associated with broad health benefits, including decreased risk of obesity and ill health (cardiovascular disease, blood glucose and type II diabetes). However, the association between plant-based diets and mood disorders such as depression remains largely equivocal. This cross-sectional study of 219 adults aged 18-44 (M=31.22, SD=7.40) explored the associations between an estimate of overall plant-based diet quality and depression in vegans (n=165) and vegetarians (n=54). Overall plant-based diet quality was associated with depressive symptoms in vegans and vegetarians F(1, 215)=13.71, p<0.001 accounting for 6% of the variation in depressive symptoms. For those without depression, higher diet quality was protective against depressive symptoms F(1, 125)=6.49, p=0.012. Conversely, for those with depression no association with diet quality was found F(1, 89)=0.01, p=0.963. These findings suggest that a high-quality plant-based diet may be protective against depressive symptoms in vegans and vegetarians. In line with emerging research between food and mental health, higher-quality dietary patterns are associated with a reduced risk of depressive symptoms. Given the rapidly increasing rate of vegan and vegetarian food products within Australia, understanding the potential mechanisms of effects through which a plant-based diet may influence depressive symptoms is required.
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Cross-sectional associations of schoolchildren's fruit and vegetable consumption, and meal choices, with their mental well-being: a cross-sectional study.
Hayhoe, R, Rechel, B, Clark, AB, Gummerson, C, Smith, SJL, Welch, AA
BMJ nutrition, prevention & health. 2021;4(2):447-462
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There has been an increase in mental health issues among school children in recent years. The importance of good nutrition for the physical and mental well-being of school children cannot be overstated. According to previous research, a diet high in processed foods, refined carbohydrates, and saturated fat are associated with mental health issues in children, while a diet high in fruits and vegetables may protect against mental health problems. The purpose of this cross-sectional study was to evaluate the relationship between dietary choices and mental well-being among primary and secondary school children. Among secondary school children, higher consumption of fruits and vegetables was associated with a greater sense of well-being, with those who consumed five or more fruits and vegetables reporting a higher sense of well-being. The well-being scores of secondary school children who consumed no breakfast and those who consumed high-energy drinks were lower than those of secondary school children who consumed conventional breakfast. Similarly, compared to children who had packed lunches, children who had no lunch had lower well-being. Among primary school children, higher intakes of fruits and vegetables were not significantly associated with well-being, whereas the type of lunch and breakfast were significantly associated with well-being. A comprehensive investigation is required to understand how dietary strategies and their components contribute to children's well-being and their modulating effects on various mechanisms. This research can be used by healthcare professionals to gain a better understanding of how a child's mental and physical health is impacted by their nutrition.
Abstract
BACKGROUND Poor mental well-being is a major issue for young people and is likely to have long-term negative consequences. The contribution of nutrition is underexplored. We, therefore, investigated the association between dietary choices and mental well-being among schoolchildren. METHODS Data from 7570 secondary school and 1253 primary school children in the Norfolk Children and Young People Health and Well-being Survey, open to all Norfolk schools during October 2017, were analysed. Multivariable linear regression was used to measure the association between nutritional factors and mental well-being assessed by the Warwick-Edinburgh Mental Well-being Scale for secondary school pupils, or the Stirling Children's Well-being Scale for primary school pupils. We adjusted all analyses for important covariates including demographic, health variables, living/home situation and adverse experience variables. RESULTS In secondary school analyses, a strong association between nutritional variables and well-being scores was apparent. Higher combined fruit and vegetable consumption was significantly associated with higher well-being: well-being scores were 3.73 (95% CI 2.94 to 4.53) units higher in those consuming five or more fruits and vegetables (p<0.001; n=1905) compared with none (n=739). The type of breakfast or lunch consumed was also associated with significant differences in well-being score. Compared with children consuming a conventional type of breakfast (n=5288), those not eating any breakfast had mean well-being scores 2.73 (95% CI 2.11 to 3.35) units lower (p<0.001; n=1129) and those consuming only an energy drink had well-being scores 3.14 (95% CI 1.20 to 5.09) units lower (p=0.002; n=91). Likewise, children not eating any lunch had well-being scores 2.95 (95% CI 2.22 to 3.68) units lower (p<0.001; 860) than those consuming a packed lunch (n=3744). In primary school analyses, the type of breakfast or lunch was associated with significant differences in well-being scores in a similar way to those seen in secondary school data, although no significant association with fruit and vegetable intake was evident. CONCLUSION These findings suggest that public health strategies to optimise the mental well-being of children should include promotion of good nutrition.
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Impact evaluation of the efficacy of different doses of vitamin D supplementation during pregnancy on pregnancy and birth outcomes: a randomised, controlled, dose comparison trial in Pakistan.
Nausheen, S, Habib, A, Bhura, M, Rizvi, A, Shaheen, F, Begum, K, Iqbal, J, Ariff, S, Shaikh, L, Raza, SS, et al
BMJ nutrition, prevention & health. 2021;4(2):425-434
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The role of vitamin D has been recognised during pregnancy, such as for calcium absorption and regulation of placental calcium transport. The aim of this study was to assess the efficacy and the pregnancy outcomes of different doses of vitamin D supplementation in pregnant women (Pakistan), where vitamin D deficiency is very high. This study is a double-blind randomised controlled trial that enrolled a total of 350 women. Study participants were randomly allocated into three groups of vitamin D3 supplementation: 4000IU/day (group A), 2000IU/day (group B) and 400IU/day (group C - control). Results indicate that vitamin D supplementation of 4000IU/day was more effective in reducing vitamin D deficiency among pregnant women and improving serum 25 Hydroxyvitamin D levels in mothers and their neonates compared with 2000IU/day and 400IU/day. Moreover, all formulations of supplementation are safe as no adverse events were reported. Authors conclude that further studies with new-borns of mothers enrolled in supplementation trials are needed particularly by focusing on the long-term outcomes and benefits of Vitamin D supplementation.
Abstract
BACKGROUND Vitamin D deficiency during pregnancy is a public health problem in Pakistan and is prevalent among most women of reproductive age in the country. Vitamin D supplementation during pregnancy is suggested to prevent adverse pregnancy outcomes and vitamin D deficiency in both the mother and her newborn. METHODS We conducted a double-blinded, randomised controlled trial in Karachi, Pakistan to evaluate the effect of different doses of vitamin D supplementation during pregnancy on biochemical markers (serum 25(OH)D, calcium, phosphorus and alkaline phosphatase) in women and neonates, and on pregnancy and birth outcomes (gestational diabetes, pre-eclampsia, low birth weight, preterm births and stillbirths). RESULTS Pregnant women (N=350) in their first trimester were recruited and randomised to three treatment groups of vitamin D supplementation: 4000 IU/day (group A, n=120), 2000 IU/day (group B, n=115) or 400 IU/day (group C, n=115). Women and their newborn in group A had the lowest vitamin D deficiency at endline (endline: 75.9%; neonatal: 64.9%), followed by group B (endline: 84.9%; neonatal: 73.7%) and then the control group (endline: 90.2%; neonatal: 91.8%). Vitamin D deficiency was significantly lower in group A than in group C (p=0.006) among women at endline and lower in both groups A and B than in the control group (p=0.001) in neonates. Within groups, serum 25(OH)D was significantly higher between baseline and endline in group A and between maternal baseline and neonatal levels in groups A and B. Participant serum 25(OH)D levels at the end of the trial were positively correlated with those in intervention group A (4000 IU/day) (β=4.16, 95% CI 1.6 to 6.7, p=0.002), with food group consumption (β=0.95, 95% CI 0.01 to 1.89, p=0.047) and with baseline levels of serum 25(OH)D (β=0.43, 95% CI 0.29 to 0.58, p<0.0001). CONCLUSION The evidence provided in our study indicates that vitamin D supplementation of 4000 IU/day was more effective in reducing vitamin D deficiency among pregnant women and in improving serum 25(OH)D levels in mothers and their neonates compared with 2000 IU/day and 400 IU/day. Trial registration number NCT02215213.
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Assessment of vitamin B12 deficiency and B12 screening trends for patients on metformin: a retrospective cohort case review.
Martin, D, Thaker, J, Shreve, M, Lamerato, L, Budzynska, K
BMJ nutrition, prevention & health. 2021;4(1):30-35
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Vitamin B12 is a water-soluble vitamin. Medications including proton pump inhibitors, histamine H2 blockers and metformin have also been shown to cause vitamin B12 deficiency. The aim of this study was to investigate the use of vitamin B12 testing in a large cohort of patients on metformin and assess the benefit to formulating screening recommendations for vitamin B12 deficiency. This study is a retrospective cohort study of 13489 patients who were exposed to metformin. Results show that patients who are greater than 65 years old and patients who have been taking metformin for more than 5 years are at increased risk of vitamin B12 deficiency. Furthermore, the African-American population was tested at a lower rate (41.62%) compared with the non-African-American population (44.9%), showing a 15% less likelihood of being tested compared with the other ethnic groups. Authors conclude that physicians should be aware of the increased incidence of vitamin B12 deficiency in particular population cohorts.
Abstract
OBJECTIVES Our study investigated the use of vitamin B12 testing in a large cohort of patients on metformin and assesses appropriateness and benefits of screening recommendations for vitamin B12 deficiency. DESIGN This retrospective cohort study included insured adult patients who had more than 1 year of metformin use between 1 January 2010 and 1 October 2016 and who filled at least two consecutive prescriptions of metformin to establish compliance. The comparison group was not exposed to metformin. Primary outcome was incidence of B12 deficiency diagnosed in patients on metformin. Secondary outcome was occurrence of B12 testing in the patient population on metformin. Records dated through 31 December 2018 were analysed. SETTING Large hospital system consisting of inpatient and outpatient data base. PARTICIPANTS A diverse, adult, insured population of patients who had more than 1 year of metformin use between 1 January 2010 and 1 October 2016 and who filled at least two consecutive prescriptions of metformin. RESULTS Of 13 489 patients on metformin, 6051 (44.9%) were tested for vitamin B12 deficiency, of which 202 (3.3%) tested positive (vs 2.2% of comparisons). Average time to test was 990 days. Average time to test positive for deficiency was 1926 days. Factors associated with testing were linked to sex (female, 47.8%), older age (62.79% in patients over 80 years old), race (48.98% white) and causes of malabsorption (7.11%). Multivariable logistic regression showed older age as the only factor associated with vitamin B12 deficiency, whereas African-American ethnicity approached significance as a protective factor. CONCLUSIONS Based on our study's findings of vitamin B12 deficiency in patients on metformin who are greater than 65 years old and have been using it for over 5 years, we recommend that physicians consider screening in these populations.
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No evidence that vitamin D is able to prevent or affect the severity of COVID-19 in individuals with European ancestry: a Mendelian randomisation study of open data.
Amin, HA, Drenos, F
BMJ nutrition, prevention & health. 2021;4(1):42-48
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Vitamin D is commonly discussed in terms of bone health and calcium and phosphate homeostasis, however, evidence has started to emerge that it may also be involved in cancer, the cardiovascular system and inflammation. The aim of this study was to assess whether genetically increased vitamin D levels are associated with SARS-CoV-2 infection risk and COVID-19 severity. This study is based on data from genome-wide association studies for vitamin D levels, vitamin D deficiency and COVID-19 incidence and severity. Results show no evidence that vitamin D is causally related to COVID-19 outcomes and there is no evidence to suggest that current National Institute for Health and Care Excellence guidance should change to support the use of vitamin D supplementation against COVID-19. Authors conclude that their findings support the recent statement by the National Institute for Health and Care Excellence that the use of vitamin D supplementation to mitigate COVID-19 is not supported by the available data.
Abstract
BACKGROUND Upper respiratory tract infections are reportedly more frequent and more severe in individuals with lower vitamin D levels. Based on these findings, it has been suggested that vitamin D can prevent or reduce the severity of COVID-19. METHODS We used two-sample Mendelian randomisation (MR) to assess the causal effect of vitamin D levels on SARS-CoV-2 infection risk and COVID-19 severity using publicly available data. We also carried out a genome-wide association analysis (GWA) of vitamin D deficiency in the UK Biobank (UKB) and used these results and two-sample MR to assess the causal effect of vitamin D deficiency on SARS-CoV-2 infection risk and COVID-19 severity. RESULTS We found no evidence that vitamin D levels causally affect the risk of SARS-CoV-2 infection (ln(OR)=0.17 (95% CI -0.22 to 0.57, p=0.39)) nor did we find evidence that vitamin D levels causally affect COVID-19 severity (ln(OR)=0.36 (95% CI -0.89 to 1.61, p=0.57)). Based on our GWA analysis, we found that 17 independent variants are associated with vitamin D deficiency in the UKB. Using these variants as instruments for our two-sample MR analyses, we found no evidence that vitamin D deficiency causally affects the risk of SARS-CoV-2 infection (ln(OR)=-0.04 (95% CI -0.1 to 0.03, p=0.25)) nor did we find evidence that vitamin D deficiency causally affects COVID-19 severity (ln(OR)=-0.24 (95% CI -0.55 to 0.08, p=0.14)). CONCLUSIONS In conclusion, we found no evidence that vitamin D is protective against SARS-CoV-2 infection or COVID-19 severity. Our data support the recent statement by the National Institute for Health and Care Excellence that the use of vitamin D supplementation to mitigate COVID-19 is not supported by the available data.
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Vitamin D supplementation for the treatment of COVID-19: a living systematic review.
Stroehlein, JK, Wallqvist, J, Iannizzi, C, Mikolajewska, A, Metzendorf, MI, Benstoem, C, Meybohm, P, Becker, M, Skoetz, N, Stegemann, M, et al
The Cochrane database of systematic reviews. 2021;5:CD015043
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This study is part of a series of Cochrane Reviews investigating treatments and therapies for coronavirus disease 2019 (COVID-19). COVID-19 is a rapidly spreading infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therapeutic interventions to treat COVID-19 are being investigated with immense emphasis. Recently, vitamin D supplementation for treatment of COVID-19 gained attention, since studies suggested an association between vitamin D deficiency and risk or prognosis of the disease. The aim of this study was to assess whether vitamin D supplementation is effective and safe for the treatment of COVID-19 This study is a living systematic review of seven records (three randomised controlled studies – 356 adult participants). Results for the effectiveness of vitamin D supplementation for participants with COVID-19 are inconclusive. Moreover, inconsistency in the reporting of adverse and serious adverse events impeded evaluation of safety of vitamin D supplementation. Authors conclude that to elucidate the effectiveness and safety of vitamin D supplementation for individuals with COVID-19, more randomised controlled trials are needed.
Abstract
BACKGROUND The role of vitamin D supplementation as a treatment for COVID-19 has been a subject of considerable discussion. A thorough understanding of the current evidence regarding the effectiveness and safety of vitamin D supplementation for COVID-19 based on randomised controlled trials is required. OBJECTIVES To assess whether vitamin D supplementation is effective and safe for the treatment of COVID-19 in comparison to an active comparator, placebo, or standard of care alone, and to maintain the currency of the evidence, using a living systematic review approach. SEARCH METHODS We searched the Cochrane COVID-19 Study Register, Web of Science and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions to 11 March 2021. SELECTION CRITERIA We followed standard Cochrane methodology. We included randomised controlled trials (RCTs) evaluating vitamin D supplementation for people with COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies investigating preventive effects, or studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)). DATA COLLECTION AND ANALYSIS We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane risk of bias tool (ROB 2) for RCTs. We rated the certainty of evidence using the GRADE approach for the following prioritised outcome categories: individuals with moderate or severe COVID-19: all-cause mortality, clinical status, quality of life, adverse events, serious adverse events, and for individuals with asymptomatic or mild disease: all-cause mortality, development of severe clinical COVID-19 symptoms, quality of life, adverse events, serious adverse events. MAIN RESULTS We identified three RCTs with 356 participants, of whom 183 received vitamin D. In accordance with the World Health Organization (WHO) clinical progression scale, two studies investigated participants with moderate or severe disease, and one study individuals with mild or asymptomatic disease. The control groups consisted of placebo treatment or standard of care alone. Effectiveness of vitamin D supplementation for people with COVID-19 and moderate to severe disease We included two studies with 313 participants. Due to substantial clinical and methodological diversity of both studies, we were not able to pool data. Vitamin D status was unknown in one study, whereas the other study reported data for vitamin D deficient participants. One study administered multiple doses of oral calcifediol at days 1, 3 and 7, whereas the other study gave a single high dose of oral cholecalciferol at baseline. We assessed one study with low risk of bias for effectiveness outcomes, and the other with some concerns about randomisation and selective reporting. All-cause mortality at hospital discharge (313 participants) We found two studies reporting data for this outcome. One study reported no deaths when treated with vitamin D out of 50 participants, compared to two deaths out of 26 participants in the control group (Risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.13). The other study reported nine deaths out of 119 individuals in the vitamin D group, whereas six participants out of 118 died in the placebo group (RR 1.49, 95% CI 0.55 to 4.04]. We are very uncertain whether vitamin D has an effect on all-cause mortality at hospital discharge (very low-certainty evidence). Clinical status assessed by the need for invasive mechanical ventilation (237 participants) We found one study reporting data for this outcome. Nine out of 119 participants needed invasive mechanical ventilation when treated with vitamin D, compared to 17 out of 118 participants in the placebo group (RR 0.52, 95% CI 0.24 to 1.13). Vitamin D supplementation may decrease need for invasive mechanical ventilation, but the evidence is uncertain (low-certainty evidence). Quality of life We did not find data for quality of life. Safety of vitamin D supplementation for people with COVID-19 and moderate to severe disease We did not include data from one study, because assessment of serious adverse events was not described and we are concerned that data might have been inconsistently measured. This study reported vomiting in one out of 119 participants immediately after vitamin D intake (RR 2.98, 95% CI 0.12 to 72.30). We are very uncertain whether vitamin D supplementation is associated with higher risk for adverse events (very low-certainty). Effectiveness and safety of vitamin D supplementation for people with COVID-19 and asymptomatic or mild disease We found one study including 40 individuals, which did not report our prioritised outcomes, but instead data for viral clearance, inflammatory markers, and vitamin D serum levels. The authors reported no events of hypercalcaemia, but recording and assessment of further adverse events remains unclear. Authors administered oral cholecalciferol in daily doses for at least 14 days, and continued with weekly doses if vitamin D blood levels were > 50 ng/mL. AUTHORS' CONCLUSIONS There is currently insufficient evidence to determine the benefits and harms of vitamin D supplementation as a treatment of COVID-19. The evidence for the effectiveness of vitamin D supplementation for the treatment of COVID-19 is very uncertain. Moreover, we found only limited safety information, and were concerned about consistency in measurement and recording of these outcomes. There was substantial clinical and methodological heterogeneity of included studies, mainly because of different supplementation strategies, formulations, vitamin D status of participants, and reported outcomes. There is an urgent need for well-designed and adequately powered randomised controlled trials (RCTs) with an appropriate randomisation procedure, comparability of study arms and preferably double-blinding. We identified 21 ongoing and three completed studies without published results, which indicates that these needs will be addressed and that our findings are subject to change in the future. Due to the living approach of this work, we will update the review periodically.