Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: a double-blind randomised controlled trial.

BACKGROUND: COVID-19 has caused morbidity, hospitalisation and mortality worldwide. Despite effective vaccines, there is still a need for effective treatments, especially for people in the community. Dietary supplements have long been used to treat respiratory infections, and preliminary evidence indicates some may be effective in people with COVID-19. We sought to evaluate whether a combination of vitamin C, vitamin D3, vitamin K2 and zinc could improve overall health and decrease symptom burden in outpatients diagnosed with COVID-19. METHODS: Participants were randomised to receive either vitamin C (6 g), vitamin D3 (1000 units), vitamin K2 (240 µg) and zinc acetate (75 mg) or placebo daily for 21 days and were followed for 12 weeks. An additional loading dose of 50 000 units vitamin D3 (or placebo) was given on day one. The primary outcome was participant-reported overall health using the EuroQol Visual Assessment Scale summed over 21 days. Secondary outcomes included health status, symptom severity, symptom duration, delayed return to usual health, frequency of hospitalisation and mortality. RESULTS: 90 patients (46 control, 44 treatment) were randomised. The study was stopped prematurely due to insufficient capacity for recruitment. The mean difference (control-treatment) in cumulative overall health was -37.4 (95% CI -157.2 to 82.3), p=0.53 on a scale of 0-2100. No clinically or statistically significant differences were seen in any secondary outcomes. INTERPRETATION: In this double-blind, placebo-controlled, randomised trial of outpatients diagnosed with COVID-19, the dietary supplements vitamin C, vitamin D3, vitamin K2 and zinc acetate showed no clinically or statistically significant effects on the documented measures of health compared with a placebo when given for 21 days. Termination due to feasibility limited our ability to demonstrate the efficacy of these supplements for COVID-19. Further research is needed to determine clinical utility. TRIAL REGISTRATION NUMBER: NCT04780061.

Mistletoe Extracts during the Oncological Perioperative Period: A Systematic Review and Meta-Analysis of Human Randomized Controlled Trials.

BACKGROUND: We aim to evaluate the safety and efficacy of mistletoe extract (ME) use during the oncological perioperative period. METHODS: Details registered a priori on PROSPERO (CRD42018086168). RESULTS: Seven RCTs (comprising 663 participants in nine reports) and three nonrandomized studies were included. In five RCTs, ME was evaluated as adjunctive care and the control group had no additional intervention, whereas in two RCTs, ME was compared head-to-head against common cancer treatments (i.e., etoposide or bacillus Calmette-Guérin) with the intervention groups not receiving standard care. Meta-analyses found no evidence for a difference between ME and no added therapy for mortality and recurrence (RR, 95% CI: 1.00, 0.79-1.27; and 1.03, 0.79-1.33, respectively). Two RCTs reported beneficial effects of ME on immune cells, specifically natural killer cells, in colorectal cancer, and one RCT reported quality of life improvement. Two RCTs reported ME discontinuations due to adverse events and grade 3/4 toxicities. Nevertheless, no safety signals were detected from these 10 studies. Quality appraisal revealed a substantial risk of bias. CONCLUSIONS: Preliminary data are encouraging for mistletoe extracts, particularly in the context of colorectal cancer. However, the evidence is limited by the number of studies, an evaluation of different outcomes, and methodological limitations. Further high-quality research is warranted.

Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: study protocol for a randomised, double-blind, placebo controlled clinical trial.

INTRODUCTION: COVID-19 has caused morbidity, hospitalisations and deaths worldwide. Despite four approved vaccines for COVID-19 in Canada, there is still a need for effective treatments, especially for people in the community. Vaccine efficacy is not 100% and long-term efficacy is still unknown. Furthermore, there are challenges to herd immunity including vaccine hesitancy and underlying conditions preventing vaccination. We aim to explore if the nutrients vitamin C, vitamin D, vitamin K2 and zinc are an effective treatment option for outpatients diagnosed with COVID-19. The primary outcome is the difference in participant-reported overall health; secondary outcomes include the effect on health status, symptom severity and duration, frequency and length of hospitalisations and mortality. METHODS AND ANALYSIS: This study is a two-arm, parallel-group, double-blind, placebo-controlled, phase III randomised controlled trial. 200 patients will be recruited remotely from COVID-19 test centres in Ottawa, Canada associated with The Ottawa Hospital. Overall health will be measured using the EuroQol Visual Assessment Scale; health status will be measured using the EuroQol 5-dimension 5-level questionnaire; symptom severity and duration will be measured using an independently developed questionnaire; analyses will use an area under the curve approach and compare mean scores using unadjusted t tests. Study data will be recorded on electronic case report forms using the Research Electronic Data Capture platform. An independent data safety and monitoring board will perform ongoing review of the study for feasibility and safety. ETHICS AND DISSEMINATION: This study has received ethical approval from the research ethics boards of the Canadian College of Naturopathic Medicine and the Ottawa Health Sciences Network, as well as regulatory approval from the Therapeutic Products Directorate and Natural and Non-Prescription Health Products Directorate of Health Canada. Results will be published in a peer-reviewed scientific journal with open access. TRIAL REGISTRATION NUMBER: NCT04780061.

Probiotics Evaluation in Oncological Surgery: A Systematic Review of 36 Randomized Controlled Trials Assessing 21 Diverse Formulations.

BACKGROUND: Objectives were to evaluate probiotics safety and efficacy in oncological surgery. METHODS: Systematic review methodology guided by Cochrane, PRISMA, SWiM, and CIOMS. Protocol registered on PROSPERO (CRD42018086168). RESULTS: 36 RCTs (on 3305 participants) and 6 nonrandomized/observational studies were included, mainly on digestive system cancers. There was evidence of a beneficial effect on preventing infections, with 70% of RCTs' (21/30) direction of effect favoring probiotics. However, five RCTs (17%) favored controls for infections, including one trial with RR 1.57 (95% CI: 0.79, 3.12). One RCT that changed (balanced) its antibiotics protocol after enrolling some participants had mortality risk RR 3.55 (95% CI: 0.77, 16.47; 7/64 vs. 2/65 deaths). The RCT identified with the most promising results overall administered an oral formulation of Lactobacillus acidophilus LA-5 + Lactobacillus plantarum + Bifidobacterium lactis BB-12 + Saccharomyces boulardii. Methodological quality appraisals revealed an overall substantial risk-of-bias, with only five RCTs judged as low risk-of-bias. CONCLUSIONS: This large evidence synthesis found encouraging results from most formulations, though this was contrasted by potential harms from a few others, thus validating the literature that "probiotics" are not homogeneous microorganisms. Given microbiome developments and infections morbidity, further high-quality research is warranted using those promising probiotics identified herein.

Are Supplemental Branched-Chain Amino Acids Beneficial During the Oncological Peri-Operative Period: A Systematic Review and Meta-Analysis.

BACKGROUND: Branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) are essential amino acids involved in immune responses, and may have roles in protein malnutrition and sarcopenia. Furthermore, certain liver diseases have been associated with a decreased Fischer's ratio (BCAAs to aromatic amino acids; phenylalanine, tyrosine, and tryptophan). We aimed to evaluate the safety and efficacy of BCAAs use in patients with cancer undergoing surgery. METHODS: MEDLINE, Embase, and CENTRAL were searched (inception to July 24, 2020) for randomized controlled trials (RCTs) and comparative observational studies in English evaluating BCAAs (alone or in combinations) during the oncological peri-operative period. Study selection, data extraction, and quality appraisal were done in duplicate. RCT risk-of-bias was appraised using Cochrane Risk-of-Bias tool, and observational studies' quality assessment was conducted with Newcastle-Ottawa Scale. Meta-analyses were conducted when appropriate. RESULTS: 20 articles were included comprising 13 RCTs and 6 observational cohort studies in 7 reports and 2019 total participants overall. Among 13 RCTs, 77% involved liver cancer. Methodological study quality scored substantial risk-of-bias across most RCTs. Meta-analysis of RCTs found a 38% decreased risk of post-operative infections in BCAAs group compared to controls (RR = 0.62; 95% CI = 0.44 to 0.87; P = .006; number of RCTs, k = 6; total sample size, N = 389; I2 = 0%). BCAAs were also found to be beneficial for ascites (RR = 0.55; 95% CI = 0.35 to 0.86; P = .008; k = 4; N = 296; I2 = 0%), body weight (MD = 3.24 kg; 95% CI = 0.44 to 6.04; P = .02; k = 3; N = 196; I2 = 24%), and hospitalization length (MD = -2.07 days; 95% CI = -3.97 to -0.17; P = .03; k = 5; N = 362; I2 = 59%). No differences were found between BCAAs and controls for mortality, recurrence, other post-operative complications (liver failure, edema, pleural effusion), blood loss, quality of life, ammonia level, and prothrombin time. No serious adverse events were related to BCAAs; however, serious adverse events were reported due to intravenous catheters. No safety concerns from observational studies were identified. CONCLUSIONS: Branched-chain amino acids during the oncological surgical period demonstrated promise in reducing important post-operative morbidity from infections and ascites compared to controls. Blinded, placebo-controlled confirmatory trials of higher methodological quality are warranted, especially using oral, short-term BCAAs-enriched supplements within the context of recent ERAS programs. PROSPERO REGISTRATION: CRD42018086168.

A Prospective Outcomes Pilot Evaluation of Inspire Now: A Program for People with Lung Cancer.

BACKGROUND: Lung cancer is the leading cause of cancer mortality in Canada, yet patients are often under-supported. A six-week program called Inspire Now, created to address unmet supportive care needs, was evaluated in this study. Feasibility and preliminary outcomes were assessed in order to inform future changes to the program. OBJECTIVES: (1) Assess the feasibility of the program and its evaluation; (2) pilot the collection of patient-reported outcomes; (3) identify outcomes that may be positively influenced; and (4) inform program modifications. METHODS: Participants were recruited from the first session of Inspire Now for an observational pilot study. The primary outcome was feasibility. Secondary outcomes included within-person changes in Functional Assessment of Cancer Therapy - Lung (FACT-L) and Measure Yourself Concerns and Wellbeing (MYCaW), and program satisfaction and qualitative experiences of participants and facilitators through internally-developed questionnaires and semi-structured interviews. Analysis was primarily descriptive, within person changes in FACT-L and MYCaW were analyzed using the Wilcoxon signed-rank test and qualitative data was assessed for common themes. RESULTS: The program and its evaluation were feasible; 8 of 9 (89%) participants consented to the study, median attendance was 6 of 6 sessions (IQR 4.5-6), and questionnaire completion was 100% at baseline and 75% at follow-up. There were clinically meaningful improvements in MYCaW concern 1 (-1.2, 95% CI -2.0 to -0.4) and overall wellbeing (-0.9, 95% CI -2.1 to 0.4). Seven of eight FACT-L sub-sections trended toward improvement, with absolute changes ranging from -1.7 to 10.8%. Participant feedback was overwhelmingly positive; group support and social interactions were highly valued. CONCLUSIONS: The group intervention for people with lung cancer was feasible to both run and evaluate. Participants responded positively to the program. Findings will inform changes to future sessions and an analysis of multiple sessions is planned.

Naturopathic Oncology Care for Pediatric Cancers: A Practice Survey.

Background: The majority of pediatric oncology patients report use of complementary and alternative medicine. Some naturopathic doctors (NDs) provide supportive pediatric oncology care; however, little information exists to formally describe this clinical practice. A survey was conducted with members of the Oncology Association of Naturopathic Physicians (OncANP.org) to describe recommendations across four therapeutic domains: natural health products (NHPs), nutrition, physical medicine, and mental/emotional support. Results: We had 99 respondents with a wide variance of clinical experience and aptitude to treat children with cancer. Of the majority (52.5%) of respondents who choose not to treat these children, the three primary reasons for this are lack of public demand (45.1%), institutional or clinic restrictions (21.6%), and personal reasons/comfort (19.6%). The 10 most frequently considered NHPs by all NDs are fish-derived omega-3 fatty acid (83.3%), vitamin D (83.3%), probiotics (82.1%), melatonin (73.8%), vitamin C (72.6%), homeopathic Arnica (69.0%), turmeric/curcumin (67.9%), glutamine (66.7%), Astragalus membranaceus (64.3%), and Coriolus versicolor/PSK (polysaccharide K) extracts (61.9%). The top 5 nutritional recommendations are anti-inflammatory diets (77.9%), dairy restriction (66.2%), Mediterranean diet (66.2%), gluten restriction (61.8%), and ketogenic diet (57.4%). The top 5 physical modality interventions are exercise (94.1%), acupuncture (77.9%), acupressure (72.1%), craniosacral therapy (69.1%), and yoga (69.1%). The top 5 mental/emotional interventions are meditation (79.4%), art therapy (77.9%), mindfulness-based stress reduction (70.6%), music therapy (70.6%), and visualization therapy (67.6%). Conclusion: The results of our clinical practice survey highlight naturopathic interventions across four domains with a strong rationale for further inquiry in the care of children with cancer.