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.
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.
Should I Recommend Vitamin D Supplements to Protect Against COVID-19?
Recent narrative reviews have recommended vitamin D supplementation as a means of reducing the risk of catching or becoming ill from the SARS-CoV-2 (i.e. the virus that causes COVID-19). There is currently not enough evidence to indicate that vitamin D supplements can prevent or improve the course of COVID-19.
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.
For a full evaluation of the evidence, including the references, see the PEN Trending Topic: Can Vitamin D Supplements Prevent or Improve the Course of COVID-19?
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.
New Study - Dairy and Breast Cancer Risk
Many news websites, including CTV (1), reported on a study (2) that looked at soy and dairy consumption and breast cancer risk. The study, which is part of the Adventist Health Study-2 (3), followed 52,795 North American women (mean age 57.1 years; free of cancer at study onset) for 7.9 years (between 2002 to 2007) who had a high average soy consumption. Self-reported food frequency questionnaires and 24-hour recalls were used to assess dietary intakes at entry into the study.
There were 1,057 new breast cancer cases found via North American cancer registries during the study time (2). Intakes of dairy calories and dairy milk were associated with a slightly greater risk of breast cancer independent of soy intake (hazard ratio (HR) 1.22; 95% confidence interval (CI), 1.05 to 1.40 and HR 1.50; 95%CI, 1.22 to1.84, respectively, comparing 90th to 10th percentiles of intakes), while there were no clear associations found between soy products and breast cancer. Fat level of milks and the consumption of cheese and yogurt showed no associations with cancer. A decreased risk of breast cancer was associated when substituting median intakes of soy milk for dairy milk (HR, 0.68; 95%CI, 0.55 to 0.85). The authors concluded that as milk intake increased, so did the risk of breast cancer, when adjusted for soy intake.
An important concern about this study is that the news headline stated “One cup of milk per day associated with up to 50 per cent increase in breast cancer risk: study” (1), which is misleading since it focused on the relative risks of a rare outcome. Looking at the absolute risks (which is a better way to report these results since the cancer was rare), the risk of cancer in this study was 2% (2 cases per 100 women) and 3% (3 cases per 100 women) among women who drank milk (HR=1.50). The absolute risk difference is 1%, so the headline stating 50% increase is reporting a statistic that suggests a big risk. Reporting the absolute risk difference (1%) gives more relevant information on the actual risk for an individual (4).
When analyzing this study there are a few limitations that should be considered. This is an observational study, so cause and effect cannot be established. Dietary intakes were self-reported and only measured once at baseline, so there is room for errors and omissions. The study did not adjust for social determinants of health or quantities of moderate or total physical activity, quantity of alcohol consumed or amounts smoked (the authors only controlled for vigorous activity, duration of alcohol use and smoking ever or never), so some or all of these variables could confound the results.
These results contrast with findings reported by the American Institute for Cancer Research (5) and an overview of systematic reviews (6), which found no consistent associations between dairy products or milk intake and the risk of postmenopausal breast cancer and actually observed a reduced risk of premenopausal breast cancer.
The authors of the study comment that dairy milk does have positive nutritional qualities and suggest that more research is needed to understand whether there is a true link between dairy intake, or other closely-related unidentified factor(s), and breast cancer risk. Until further research is available, dietitians can continue to review healthy lifestyle behaviours with clients including eating a balanced and varied diet that includes lots of vegetables, fruit and whole grain foods; engaging in regular physical activity; and avoiding smoking. Refer to the PEN client handout: Cancer Prevention Eating Guidelines.
- Bogart N. One cup of milk per day associated with up to 50 percent increase in breast cancer risk: study. CTV News. February 25, 2020. [cited 2020 Feb 27]. Available from: https://www.ctvnews.ca/health/one-cup-of-milk-per-day-associated-with-up-to-50-per-cent-increase-in-breast-cancer-risk-study-1.4826979
- Fraser GE, Jaceldo-Sielg K, Orlich M, Mashak A, Sirirat R, Knutsen S. Dairy, soy, and risk of breast cancer: those confounded milks. Int J Epidemiol. 2020 Feb; pii: dyaa007. doi: 10.1093/ije/dyaa007. Available from: https://www.ncbi.nlm.nih.gov/pubmed/32095830
- Loma Linda University Health. Adventist Health Study-2. 2020. [cited 2020 Feb 27]. Available from: https://adventisthealthstudy.org/
- Noordzij M, van Diepen M, Caskey FC, Jager JK. Relative risk versus absolute risk: one cannot be interpreted without the other. Nephrol Dial Transplant. 2017 Apr;32(suppl 2): :ii13-ii18. doi: 10.1093/ndt/gfw465. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/?term=28339913
- American Institute for Cancer Research. Key findings. Diet, nutrition, physical activity and breast cancer. Revised 2018. Available from: https://www.aicr.org/research/the-continuous-update-project/breast-cancer/
- Jeyaraman M, Abou-Setta, Grane L, Farshidfar F, Copstein L, et al. Dairy product consumption and development of cancer: an overview of reviews. BMJ Open. 2019 Jan;9(1):e023625. doi: 10.1136/bmjopen-2018-023625. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30782711
Addressing Stigma: Towards a More Inclusive Health System
The Chief Public Health Officer’s Report on the State of Public Health in Canada in 2019 includes information about trends and the need to provide trusted, evidence-based information to Canadians. The report summarizes Canadian health status in terms of mental illness, substance use, tuberculosis, HIV, obesity, vaccine coverage, sexually transmitted infections, youth vaping, youth cigarette smoking and the opioid crisis. The report also addresses stigma that affects health including stigma experienced by First Nations, Inuit, and Métis peoples, African, Caribbean and Black Canadians, seniors and members of the LGBTQ2+ people.
The report was developed based on stakeholder engagement and evidence reviews conducted of social and health science databases. Interviews and discussions involved >90 leaders from across Canada, which included individuals with lived experience, policy-makers, researchers, clinicians and administrators. It presents a new Action Framework for Building an Inclusive Health System to explore how stigma can be addressed.
See Additional Content: Weight Stigma Background.
Vitamin D Update: Supplementation and Pregnancy and Perinatal Outcomes and 25-hyroxy-vitamin D as a Marker for Nutrient Deficiency and Sufficiency
Vitamin D has been a very active area of research in recent decades. Not only have there been numerous research studies published, there have also been numerous systematic reviews published summarizing these studies. Recently, researchers in Alberta, Canada undertook a systematic review of the systematic reviews that investigated the importance of vitamin D in pregnancy for important perinatal and infant outcomes (1).
This systematic review of systematic reviews found 42 systematic reviews of 204 primary studies that evaluated either vitamin D supplementation in pregnant women and/or examined the association between serum vitamin D levels for at least one predefined perinatal outcome (1). The researchers evaluated the systematic reviews for research quality using the AMSTAR tool and only analyzed data from the 13 systematic reviews with high AMSTAR scores.
The systematic reviews of randomized controlled trials (RCTs) with the highest quality of evidence showed no benefits from vitamin D supplementation regarding preterm birth, preeclampsia, gestational diabetes, stillbirth, low birth weight or caesarean section (1). A significant difference was found for small-for-gestational age; however, this evidence was low quality for two reasons: 1) the high risks of bias in the included studies without an accompanying sensitivity analysis to examine the low risk of bias studies separately, and 2) imprecision due to the small numbers of small-for-gestational age births in the included studies. Systematic reviews of observational studies showed that women with low 25-hyroxy-vitamin D levels had higher rates of preterm birth, preeclampsia, gestational diabetes and small-for-gestational age.
The findings of this systematic review (1) reinforce the findings of a 2017 systematic review (2) that found that the superior health of people with higher vitamin D serum levels suggested by the frequent associations observed in observational studies are not seen in randomized trials of vitamin D supplementation. Additionally, there is increasing evidence that serum 25-hyroxy-vitamin D, the vitamin D status marker, is a negative acute phase reactant, which decreases in response to other variables (2-9). Specifically, researchers have observed that 25-hyroxy-vitamin D decreases in response to inflammation (3), acute illness (4), ill health (2), critical illness (5), surgery (6,7) and when C-reactive protein increases (3,7-9). If a marker changes in response to other variables, then it has limited use as a nutritional adequacy marker.
- Bialy L, Fenton T, Shulhan-Kilroy J, Johnson DW, McNeil DA, Hartling L. Vitamin D supplementation to improve pregnancy and perinatal outcomes: an overview of 42 systematic reviews. BMJ Open. 2020 Jan 20;10(1):e032626. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/31964667
- Autier P, Mullie P, Macacu A, Dragomir M, Boniol M, Coppens K, et al. Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol. 2017 Dec;5(12):986-1004. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/29102433
- McMillan DC, Maguire D, Talwar D. Relationship between nutritional status and the systemic inflammatory response: micronutrients. Proc Nutr Soc. 2019 Feb;78(1):56-67. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/30220267
- Kostoglou-Athanassiou I, Pantazi E, Kontogiannis S, Kousouris D, Mavropoulos I, Athanassiou P. Vitamin D in acutely ill patients. J Int Med Res. 2018 Oct;46(10):4246-57. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/30157690
- Czarnik T, Czarnik A, Gawda R, Gawor M, Piwoda M, Marszalski M, et al. Vitamin D kinetics in the acute phase of critical illness: a prospective observational study. J Crit Care. 2018 Feb;43:294-9. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/28968524
- Binkley N, Coursin D, Krueger D, Iglar P, Heiner J, Illgen R, et al. Surgery alters parameters of vitamin D status and other laboratory results. Osteoporos Int. 2017 Mar;28(3):1013-20. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/27826645
- Waldron JL, Ashby HL, Cornes MP, Bechervaise J, Razavi C, Thomas OL, et al. Vitamin D: a negative acute phase reactant. J Clin Pathol. 2013 Jul;66(7):620-2. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/?term=23454726
- Kruit A, Zanen P. The association between vitamin D and C-reactive protein levels in patients with inflammatory and non-inflammatory diseases. Clin Biochem. 2016 May;49(7-8):534-7. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/?term=26778547
- Silva MC, Furlanetto TW. Does serum 25-hydroxyvitamin D decrease during acute-phase response? A systematic review. Nutr Res. 2015 Feb;35(2):91-6. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/?term=25631715
Can Selenium-rich Lentils Reduce Arsenic Toxicity in Chronically-Exposed Individuals?
New research examined the use of selenium-rich lentils as a method to reduce arsenic toxicity and arsenic levels in biological samples, and to improve health indicators in those with chronic exposure to arsenic from water and food.
A double-blind, cluster-randomized, placebo-controlled trial of 405 healthy Bangladesh people (14 to 75 years of age) with chronic exposure to arsenic was conducted (1). The intervention group (204 participants) was provided with 65 gm of selenium-rich lentils containing 55 μg selenium/day and the control group (201 participants) were provided with the same amount of lentils but of with low selenium levels (1.5 ug selenium/day). At baseline, three and six months, total arsenic levels were measured from urine, stool and blood samples and anthropometric measurements were taken. Hair samples were also taken at baseline and at six months follow up. Participants who consumed the selenium-rich lentils were found to be excreting more arsenic in their urine (measured as arsenic metabolite (dimethylasrsinic acid)) at six months compared to the control group (P=0.008). Some health indicators, including the incidence of allergy (P=0.02) and asthma (P=0.05), were lower in the intervention group compared to the control group, and body mass index was higher (P<0.01) (the participants’ average BMI was 22). The authors suggested that selenium-rich lentils can increase arsenic excretion and improve the health indicators among people with high arsenic exposure. They recommended longer term larger scale studies be conducted to verify these results and to examine if higher concentrations of selenium would provide additional health benefits.
For additional information on the potential health effects of consuming arsenic, see the following PEN Content:
Is the consumption of rice (white and brown) associated with increased arsenic-related health risks?
Food Safety - Arsenic in Rice Background
Trending Topic - Do New Parents or Parents-to-be Need to be Concerned with Dietary Arsenic Exposure?
- Smits JE, Krohn RM, Akhtar E, Hore SK, Yunus M, Vandenberg A, et al. Food as medicine: selenium enriched lentils offer relief against chronic arsenic poisoning in Bangladesh. Environ Res. 2019 Sept;176:108561. Abstract available from: https://www.ncbi.nlm.nih.gov/pubmed/31299617
Food Trends in 2020
Registered dietitians, chefs and the food industry weigh in on expected food trends for the coming year. Common themes are an expected growth in the number of CBD-infused beverages and food products (particularly in Britain and Canada), more plant-based foods and alternative meat options, growing number of 'flexitarians' (those who follow a minimally plant-based diet) and considerations given to sustainable choices. Check out a few of our favourite predictions:
Happy New Year!
Trending Topic - Why Are Journal Article Retractions Important to Practitioners?
Dairy Intake, Mortality and CVD - The Debate Continues
Trending Topic - Recent Research on Vitamin D