Trending Topics pieces (Article Analyses, Evidence Clips and Other Topics) are published in timely response to recent media and journal articles, position statements, clinical guidelines, etc. Since they are based on the most recent evidence/publications, they may not be consistent with PEN evidence in other PEN content areas. As soon as possible, when this occurs, the PEN content will be reviewed and updated as needed.
Vitamin D and COVID-19: Do Latest Studies Support Supplementation?
To date, research on vitamin D supplementation and COVID-19 outcomes has been limited, so the PEN Team reviewed two recent studies on vitamin D and COVID-19 to see what, if anything, has changed.
Conversations continue on social media about the potential role of vitamin D supplementation in the prevention and treatment of COVID-19. The PEN Team noticed that a common rationale was that patients with COVID-19 tended to have lower vitamin D status (25(OH)D levels). We decided to take a look at two recent studies that reported this connection to determine if the results support vitamin D supplementation to improve COVID-19 outcomes.
First, we looked at an observational study by De Smet et al. that noted that patients with COVID-19 had progressively lower 25(OH)D levels with more severe COVID respiratory disease (1). The study authors also observed that those with vitamin D deficiency were almost four times more likely to die (adjusted odds ratio [OR] 3.87; 95% confidence interval [CI], 1.30 to 11.55). Vitamin D deficiency was prevalent among the patients with COVID-19 infections, more so among the men (67%) than among the women (47%). These researchers adjusted for several variables that are risk factors for COVID-19 mortality (age, ethnicity, chronic lung disease, coronary artery disease/hypertension, diabetes and extent of lung damage).
From other vitamin D research, we know that the marker for vitamin D status (25(OH)D) can be lowered by infections (2). Therefore, low 25(OH)D levels may not reflect poor vitamin D status in a person with an infection. De Smet et al. were not able to determine whether what looked like a vitamin D deficiency was actually a nutritional deficiency or whether the COVID-19 infection lowered the participants 25(OH)D, making these patients appear to have a vitamin D deficiency (1). For this reason, this observational study does not provide evidence that vitamin D supplementation would be helpful for improving outcomes of a COVID-19 infection.
The second study we examined was a randomized control trial of vitamin D supplementation in people with mild symptomatic and asymptomatic COVID-19 infections. Rastogi et al. randomized 40 people with mild COVID-19 infections to 60,000 IU/day of vitamin D3 or placebo for seven days (3). The researchers observed that more participants in the intervention group became COVID-19 RNA negative before day 21 compared to participants in the control arm (62.5% versus 20.8%, P<0.018). Vitamin D supplementation lowered fibrinogen levels significantly but not the other inflammatory markers (SARS-CoV-2 RNA, D-dimer, procalcitonin CRP and ferritin). These researchers only reported differences in indirect markers (3) and did not report World Health Organization-recommended patient-important outcomes (patient survival and patient health care system use over the course of clinical illness) (4). The PEN Team thinks that this trial does not answer the question of whether vitamin D supplementation improves COVID-19 outcomes.
What This Means
After reviewing these studies, the PEN Team has two key questions:
1. What is the relationship between vitamin D deficiency and COVID-19 severity?
2. What is the impact of vitamin D supplementation on patient-important outcomes, such as disease severity, hospitalization and death?
Before dietitians can make recommendations on the use of vitamin D supplementation to improve COVID-19 outcomes, randomized control trials examining the prevention of COVID-19 (including severe COVID-19) and the treatment of COVID-19 with patient-important outcomes are needed.
- De Smet D, De Smet K, Herroelen P, Gryspeerdt S, Martens GA. Serum 25(OH)D Level on Hospital Admission Associated With COVID-19 Stage and Mortality. Am J Clin Pathol. 2020 Nov 25:aqaa252. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717135/
- Hernández-Álvarez E, Pérez-Barrios C, Blanco-Navarro I, Pérez-Sacristán B, Donoso-Navarro E, Silvestre RA, et al. Association between 25-OH-vitamin D and C-reactive protein as a marker of inflammation and cardiovascular risk in clinical practice. Ann Clin Biochem. 2019 Jul;56(4):502-7. Available from: https://pubmed.ncbi.nlm.nih.gov/31043057/
- Rastogi A, Bhansali A, Khare N, Suri V, Yaddanapudi N, Sachdeva N, et al. Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study). Postgrad Med J. 2020 Nov 12:postgradmedj-2020-139065. Abstract available from: https://pubmed.ncbi.nlm.h.gov/33184146/
- WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020 Aug;20(8):e192-e197. Abstract available from https://pubmed.ncbi.nlm.nih.gov/32539990/
Could Eating Cabbage and Fermented Vegetables Reduce Severe Outcomes of COVID-19?
During the COVID-19 pandemic you may be getting questions from your clients about how food and nutrients may help prevent or treat the coronavirus. The following analysis by a dietetic student looks at a study in adults related to eating fermented vegetables.
A recent narrative review compared COVID-19 mortality rates between and within countries, with a nutrition lens (1). This review led the authors to hypothesize that the severity of COVID-19 outcomes may be reduced through the consumption of foods such as cabbage and fermented vegetables.
A review of two ecological studies (2,3) suggested that there was a statistically significant association between a higher consumption of cabbage, cucumber and fermented vegetables and lower COVID-19 mortality rates. While there are notable limitations to ecological research (further discussed below), it is biologically plausible that cabbage and fermented vegetables could have a protective role on COVID-19 outcomes. The sulforaphane precursors found in cabbage and the Lactobacillus found in fermented vegetables both activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a regulator of cellular anti-oxidative response (4-6). Nrf2 has been shown to protect against many of the factors that increase the risk of severe COVID-19 outcomes, including insulin resistance, inflammation and endothelial damage (7,8). Microbiome changes of the gut resulting from live bacterial cultures in fermented vegetables might also provide protective measures against COVID-19, although further studies are needed to prove whether this is the case (9,10).
A few limitations must be considered when analyzing this article. First, the authors did not perform a robust systematic review with risk of bias assessments, given the lack of original research on the topic. Additionally, the hypothesis of this review relied heavily on data from two ecological studies (2,3), making ecological fallacy a concern. While data compiled through ecological studies can be useful in showing possible associations between variables, results may be misinterpreted for a number of reasons. Most notably, data used for ecological studies comes from populations, rather than individuals, and as such, may have been impacted by a large number of possible confounding factors. For example, COVID-19 mortality rates could be confounded by location-specific factors such as the pandemic policies in place within each country (11), proportion of frontline workers (12) or levels of chronic disease within the population (13). Furthermore, the two ecological studies (2,3) supporting the hypothesis are preprints and therefore have not yet undergone peer review.
The authors acknowledged that this review was intended to generate hypotheses for future studies. Further research is needed to determine if the consumption of cabbage, cucumber and fermented foods can reduce the severity of outcomes resulting from COVID-19.
Written by Amber Foster, BSc. Reviewed by Justine Horne, PhD, RD and Tanis Fenton, PhD, RD, FDC.
- Bousquet J, Anto JM, Czarlewski W, Haahtela T, Fonseca SC, Iaccarino G, et al. Cabbage and fermented vegetables: from death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID‐19. Allergy. 2020 [Epub ahead of print] doi.org/10.1111/all.14549. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/32762135/
- Fonseca S, Rivas I, Romaguera D, Quijal M, Czarlewski W, Vidal A, et al. Association between consumption of fermented vegetables and COVID‐19 mortality at a country level in Europe. medRxiv. 2020. doi.org/10.1101/2020.07.06.20147025. Abstract available from: https://www.medrxiv.org/content/10.1101/2020.07.06.20147025v1
- Fonseca SC, Rivas I, Romaguera D, Quijal-Zamorano M, Czarlewski W, Vidal A, et al. Association between consumption of vegetables and COVID‐19 mortality at a country level in Europe. medRxiv. 2020. doi.org/10.1101/2020.07.17.20155846. Available from: https://www.medrxiv.org/content/10.1101/2020.07.17.20155846v1
- Luang‐In V, Deeseenthum S, Udomwong P, Saengha W, Gregori M. Formation of sulforaphane and iberin products from thai cabbage fermented by myrosinase ‐ positive bacteria. Molecules. 2018;23(4):955. doi: 10.3390/molecules2304095. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/29671807/
- Yang L, Palliyaguru DL, Kensler TW. Frugal chemoprevention: targeting Nrf2 with foods rich in sulforaphane. Semin Oncol. 2016;43(1):146‐53. doi: 10.1053/j.seminoncol.2015.09.013. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/26970133/
- Senger DR, Li D, Jaminet SC, Cao S. Activation of the Nrf2 Cell defense pathway by ancient foods: disease prevention by important molecules and microbes lost from the modern western diet. PLoS One. 2016;11:e0148042. doi: 10.1371/journal.pone.0148042. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/26885667/
- Chen B, Lu Y, Chen Y, Cheng J. The role of Nrf2 in oxidative stress‐induced endothelial injuries. J Endocrinol. 2015;225(3):R83‐99. doi: 10.1530/JOE-14-0662. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/25918130/
- Xu L, Nagata N, Ota T. Glucoraphanin: a broccoli sprout extract that ameliorates obesity‐induced inflammation and insulin resistance. Adipocyte. 2018;7(3):218‐25. doi:10.1080/21623945.2018.1474669. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/29898626/
- Saad MJ, Santos A, Prada PO. Linking gut microbiota and inflammation to obesity and insulin resistance. Physiology. 2016;31(4):283‐293. doi: 10.1152/physiol.00041.2015. Available from: https://pubmed.ncbi.nlm.nih.gov/27252163/
- Zuo T, Zhang F, Lui GCY, Yeoh YK, Li AYL, Zhan H, et al. Alterations in gut microbiota of patients with COVID‐19 during time of hospitalization. Gastroenterology. 2020;159(3):944-55.e8. doi: 10.1053/j.gastro.2020.05.048. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/32442562/
- Roser M, Ritchie H, Ortiz-Ospina E, Hasell, J. Policy responses to the coronavirus pandemic. Our World in Data: Oxford (UK): 2020. Available from: https://ourworldindata.org/policy-responses-covid
- Nguyen LH, Drew DA, Graham MS, Joshi, AD, Chuan-Gou G, Ma W, et al. Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study. Lancet. 2020 Sep;5(9):475-43. doi: 10.1016/S2468-2667(20)30164-X. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/32745512/
- Sanyaolu A, Okorie C, Marinkovic A, Patidar R, Younis K, Desai P, et al. Comorbidity and its impact on patients with COVID-19. SN Compr Clin Med. 2020 Jun:1-8. doi: 10.1007/s42399-020-00363-4. Epub ahead of print. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/32838147/
Should I Recommend Vitamin D Supplements to Protect Against COVID-19? Updated November 2020
The Bottom Line:
- No studies have examined the effect of vitamin D to prevent or treat COVID-19 infections.
- Information extrapolated from randomized trials that examined respiratory tract infection prevention have not reported consistent beneficial effects of vitamin D compared to placebo in adults or children.
- Potential risks that have been identified include a higher rate of repeat episodes of pneumonia.
- While observational studies suggest that lower serum vitamin D levels are associated with inflammatory response, lower serum vitamin D levels are associated with other factors and not only with inadequate vitamin D intake.
- Vitamin D is an essential nutrient and vitamin D supplementation is recommended in a number of countries for various ages during the life cycle for general health.
COVID-19 Lockdown Associated with Weight and Dietary Changes Among Adults with Obesity
You may have heard from your clients that the pandemic lockdown has resulted in individuals feeling challenged to manage their weight. The following analysis by a dietetic student looks at a related study in adults with obesity.
In an observational study, researchers evaluated changes in weight and dietary habits among outpatients of a Northern Italian Obesity Unit after one month of a COVID-19 enforced lockdown (1). The participants (n=150), who were enrolled in a 12-month weight loss program, completed a 12-question multiple choice questionnaire. They also self-reported their weight after one month of lockdown, which was compared to a measured weight from before the lockdown period. On average, weight and BMI increased significantly (P<0.05) by 1.51 kg (3.3 lbs) and 0.58 kg/m2, respectively, during the first month of lockdown. Self-reported anxiety/depression was the strongest predictor of weight gain among the participants. Lower physical activity, boredom/solitude, enhanced eating, unhealthy eating and a lower level of education were also significantly associated with increased weight and BMI. The authors suggested that the adverse mental health effects of quarantine could be a major factor in the lifestyle changes of the participants (1), citing Ryan et al. that individuals with obesity are more likely to experience social isolation and depression (2).
There are several reasons why this study’s findings are low quality. A validated questionnaire was not used for this study and data, including follow-up weight, was self-reported. In addition, due to the nature of the study design, causation about the impact of the COVID-19 lockdown on weight and nutritional changes cannot be inferred. Moreover, generalizability of the results is limited to European adults with obesity who were participating in weight-loss counselling.
This low quality data suggests that individuals with obesity experienced weight gain during the first month of COVID-19 lockdown (1). Also in this study, self-reported anxiety/depression, lower levels of education, lower levels of exercise, higher levels of boredom/solitude, increased food consumption and the consumption of “unhealthy” foods were associated with weight gain. Further research is needed before weight-related COVID-19 clinical practice recommendations can be made.
Written by Laura Michailidis, BA Candidate. Reviewed by Justine Horne, PhD, RD and Tanis Fenton, PhD, RD, FDC.
- Pellegrini M, Ponzo V, Rosato R, Scumaci E, Goitre I, Benso A, et al. Changes in weight and nutritional habits in adults with obesity during the “lockdown” period caused by the COVID-19 virus emergency. Nutrients. 2020 Jul;12(7):2016. doi.org/10.3390/nu12072016. Abstract available from: https://pubmed.ncbi.nlm.nih.gov/32645970
- Ryan DH, Ravussin E, Heymsfield S. COVID 19 and the patient with obesity – the editors speak out. Obesity. 2020 Apr;28(5):847. doi.org/10.1002/oby.22808. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228389
COVID-19 Trials and Research We Are Watching
The Herbal Medicine for the Treatment of Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis of Randomized Controlled Trials evaluated the effectiveness and adverse events of oral herbal medicines (Chinese patent medicine: Lianhua Qingke granules, Shufeng Jiedu capsule, Jinhua Qinggan granules, Toujie Quwen granules) and herbal decoction when they were combined with Western medicines (Lopinavir/ritonavir, Arbidol Hydrochloride tablets, Chloroquine Phosphate tablets, Ambroxol Hydrochloride tablets, Moxifloxacin tablets, Interferon-alfa injections and Ribavirin injections) for the treatment of COVID-19 (seven RCTS; 855 patients from mainland China). While some significant effects of the combined therapy were found compared to Western medicine alone, poor reporting within the primary studies made it difficult to evaluate their quality and many of the outcomes had high heterogeneity (I2≥70%). More high quality RCTs are needed to further validate their effectiveness.
Vitamin D Trial
The COVIDENCE UK Study is investigating how diet and lifestyle factors might influence the transmission of SARS-CoV-2, severity of COVID-19 symptoms, speed of recovery and any long-term effects. The researchers aim to recruit at least 12,000 people and to obtain interim results by this summer.
Vitamin C Trials
A review from the Cochrane Library on Vitamin C Supplementation for Prevention and Treatment of Pneumonia of seven studies (five RCTs and two quasi-RCTs) involving a total of 2,774 participants (five studies in children and two studies in adults). The authors concluded that evidence was insufficient to determine an effect of vitamin C because of the very low quality evidence. Other good quality studies are needed to assess the role of vitamin C supplements for pneumonia prevention and treatment.
A randomized control trial published in JAMA in January 2020 showing a lack of effectiveness of intravenous vitamin C, hydrocortisone and thiamine as compared to hydrocortisone alone in a quicker resolution of septic shock suggests that intravenous vitamin C is not likely to be effective for COVID-19 treatment.
Several clinical trials examining the effect of vitamin C supplementation (both intravenous and oral) on COVID-19 treatment and prevention from around the world have been registered with the U.S. National Library of Medicine's ClinicalTrials.gov database. Two specific trials are:
- A trial from Wuhan designed to provide more definitive answers about the effectiveness of intravenous vitamin C for the treatment of severe 2019-nCoV infected pneumonia is underway with an expected completion date of September 2020. This trial is designed to provide more definitive answers about the effectiveness of intravenous vitamin C for COVID-19.
- The LOVIT (Lessening Organ Dysfunction with VITamin C ) trial is a multi-centre trial currently being conducted in Canada and with recent approval in a number of other countries as well. It aims to find out if intravenous vitamin C in high doses can improve health outcomes, particularly mortality, in septic COVID-19 patients.
A New Site - LitCOVID
LitCOVID is new from PUBMED. It is a site to help scientists keep track of COVID-19 evidence publications.
*Word of Caution from PEN Evidence Analysts: Please keep in mind that these papers are being rushed to publication as the information is wanted as soon as possible. Some of these papers are not peer reviewed. Peer reviewing is not a perfect process but it does allow an unbiased scrutiny of the work by someone external to the research group and is known to lead to better quality work. See additional information from the Canadian Broadcasting Corporation (CBC): Scientists Cut Peer-Review Corners under Pressure of COVID-19 Pandemic.
COVID-19 Trials and Research We Are Watching
Vitamin C Trials
A randomized control trial published in JAMA showing a lack of effectiveness of intravenous vitamin C, hydrocortisone and thiamine as compared to hydrocortisone alone in a quicker resolution of septic shock suggests that intravenous vitamin C is not likely to be effective for COVID-19 treatment.
A trial from the US National Library of Medicine ClinicalTrials.gov: Vitamin C Infusion for the Treatment of Severe 2019-nCoV Infected Pneumonia is underway (estimated completion September 2020). This trial is designed to provide more definitive answers about the effectiveness of intravenous vitamin C for COVID-19.
A New Site - LitCOVID
LitCOVID is new from PUBMED. It is a site to help scientists keep track of COVID-19 evidence publications.
*Word of Caution from PEN Evidence Analysts: Please keep in mind that these papers are being rushed to publication as the information is wanted ASAP. Some of these papers are not peer reviewed. While peer review is not a perfect process by any means, it does allow an unbiased review of the work by someone external to the research group.
SARS-CoV-2 Virus Stability and Disinfecting
Two recent studies have emerged on the persistence of the coronavirus on various surfaces (1,2). Using an in vitro study, Van Doremalen et al. examined how long SARS-CoV-2 virus (i.e. the virus that causes COVID-19*) remained viable on four surfaces (cardboard, plastic, stainless steel and copper) for varying lengths of time (1). At room temperature and 40% humidity, viable SARS-CoV-2 viruses were detectable up to 24 hours on cardboard and up to 72 hours on stainless steel and plastic. The virus was not viable after four hours on copper.
Kampf et al. reported a review on coronavirus persistence on surfaces and materials (2). While this second study examined coronaviruses, it did not specifically study the SARS-CoV-2 virus; the authors suggest that they expect the persistence and inactivation of this new coronavirus are likely similar. They found that coronaviruses can remain potentially infectious from two hours up to nine days on various materials. At higher air temperatures of 30 to 40 °C, persistence was reduced compared to room temperatures. The studied viruses were stable (≥28 days) at refrigerator temperature, 4 °C. Humidity influenced persistence, as coronaviruses were less stable at 30% relative humidity compared to 50% relative humidity. The researchers also found that biocidal agents including 62-71% ethanol, 0.5% hydrogen peroxide or 0.2% sodium hypochlorite (bleach - preparation instructions below) used for disinfecting inactivated coronaviruses within one minute. Other biocidal agents were noted to be less effective.
Various organizations have now recommended guidelines based on the results of the first study. These include:
- Wash your hands thoroughly with soap and water for 20 seconds before and after preparing and eating food, using the washroom, after sneezing or coughing (3). Although the risk is low, if you are concerned or if you or someone in the household is of high risk, wash your hands after handling anything that might be contaminated such as cardboard, plastic and stainless steel (4).
- Disinfect hard surfaces daily including high touch areas such door handles, light switches, counter tops, tables, keyboards, toys, phones and TV remotes using ER-approved disinfectant (3).
- Refer to Health Canada’s Hard Surface Disinfectants and Hand Sanitizers (COVID-19) for instructions and for a list of effective disinfectants. Be sure to read manufacturers’ directions on the labels of the disinfectant cleaning product as many of these need to remain in contact with the surface for a period of time (e.g. 30 seconds) to be effective (e.g. do not just spray on and wipe off) (5).
- As these products are currently hard to find because of the COVID-19 pandemic, a solution of diluted bleach can also be used as per instructions on the label of the bleach container. For 5% sodium hypochlorite bleach (the usual concentration sold in stores) use 5 mL (1 tsp) per 250 mL (1 cup) of water or 20 mL (4 tsp) per 1 litre (4 cups) of water to make a 0.2% solution (5).
- Cleaning products remove germs and dirt, lowering their numbers and reducing the risk of spreading infections (5). Products with disinfectants kill germs.
*Note: SARS-CoV-2 is the name of the virus. COVID-19 is the disease the virus causes.
- van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020 Mar 17. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/?term=32182409
- Kampf G, Todt D, Pfaender S, Steinmann E. Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents. J Hosp Infect. 2020 Mar;104(3):246-51. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/?term=32035997
- Health Canada. Coronavirus Disease (COVID-19): prevention and risks. 2020 Apr 1. Available from: https://www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/prevention-risks.html?topic=tilelink
- Harvard T.H. Chan. School of Public Health. Food Safety, nutrition, and wellness during COVID-19. 2020 Mar 25. Available from https://www.hsph.harvard.edu/nutritionsource/2020/03/25/food-safety-nutrition-and-wellness-during-covid-19/
- Health Canada. Hard surface disinfectants and hand sanitizers (COVID-19). 2020 Mar 30. Available from https://www.canada.ca/en/health-canada/services/drugs-health-products/disinfectants/covid-19.html
Immunity, Nutrition and COVID-19
Have you been asked questions regarding the COVID-19 virus, immunity and nutrition? The following resources may help you answer them, see:
The novel coronavirus is new and evidence to support specific dietetic recommendations is not yet available in the scientific literature. The bottom line is that a healthy diet rich in fruit and vegetables, protein foods and whole grains is important for a strong immune system as are other healthy lifestyle habits (e.g exercise, not smoking, adequate sleep, managing stress etc). There is no one food or nutrient, supplement or herb that will protect you from the COVID-19 virus. The WHO has stated that there is no evidence that the consumption of garlic will prevent COVID-19. For this and other myth busters see WHO's advice for the public: myth busters. For more information about how to protect yourself and others, please follow the advice of your health authorities.