BACKGROUND:In 2020, COVID-19 caused by the SARS-CoV-2 emerged as a global pandemic. Combination therapies for viral illnesses may be more effective than single-agent therapies in reducing symptoms and preventing disease progression. Repurposed drugs may offer cost-effective accessible treatment options while other novel therapies are being developed. STUDY QUESTION:To assess the safety and tolerability of a combination of repurposed drugs and supplements in the early therapy of acute nonhospitalized COVID-19 illness. STUDY DESIGN:A multicenter pilot cohort study was undertaken. Participants older than 40 years and positive for COVID-19 within 4 days of illness onset received telehealth outpatient care. The multimodal therapy of ivermectin, doxycyline, zinc, vitamin C, and vitamin D 3 was given as core therapy (group-1), or core therapy plus famotidine (group-2) for 10 days in a randomized masked controlled fashion. MEASURES AND OUTCOMES:A total of 275 participants, who were either vaccinated (n = 151) or unvaccinated (n = 124) for COVID-19, were randomized into group-1 (n = 137) or group-2 (n = 138). Four participants (1.5%) were hospitalized within the first 28 days. RESULTS:No viral rebound was experienced by any participants who took the 10-day therapy. Symptoms were reported daily until day 10, and at days 14, 28, and 90. The addition of famotidine resulted in less fatigue and nasal symptoms at day 14. These 5-component and 6-component interventions (ie, core therapy with and without famotidine) were equally safe and well tolerated. CONCLUSIONS:The multimodal therapy for acute COVID-19 was safe and well tolerated. The results justify adequately powered trials of the 5- or 6-component intervention on major early and late outcomes of COVID-19 infections.

Objectives: To assess the prevalence of Vitamin-D deficiency and respiratory illnesses in Australian adults. Methods: In a cross-sectional sample of Australian adults, serum Vitamin-D levels and frequency of cold and flu symptoms were assessed. Those with sub-optimal Vitamin-D levels (<75nmol/L) were supplied with 4000-10,000IU Vitamin-D3 daily for 3-months. Data was analyzed with ANOVA and Pearson-correlation. Results: A total of 199 adults aged 57 +/- 15 years participated in the study. A third (34 %) had optimal Vitamin-D levels at baseline, 42 % were insufficient (<75nmol/L), 19 % deficient (<50nmol/L) and 5 % severely-deficient (<25nmol/L). About half (56 %) had regularly taken Vitamin-D supplements (1000-5000IU/day) prior to the study. The prevalence of respiratory illnesses was slightly higher (70 %, mean=3-per-year) in the severely-deficientgroup compared to other Vitamin-D-groups (50 %, mean 2.5 +/- 2). Overall, the frequency of respiratory illnesses tended to be lower with higher Vitamin-D levels (group 3: r = 0.285; p = 0.009). A total of 66 participants (50 %) with sub-optimal Vitamin-D levels (n = 131) completed Vitamin-D3 supplementation. After 3-months, no participants were Vitamin-D deficient, only 15 % remained insufficient, while 85 % reached optimal Vitamin-D levels (mean 97 +/- 4nmol/L). Conclusion: Optimal Vitamin-D levels are correlated with the prevention of respiratory illnesses, and can be achieved with Vitamin-D supplementation within 3-months. Implications for public health: A large proportion of Australians are Vitamin-D deficient/insufficient. Vitamin-D supplementation is key to alleviate Vitamin-D deficiency and support Vitamin-D's role in the prevention of acute respiratory infections via the innate and adaptive immune system.

Arterial stiffness is a cardiovascular risk factor that increases with age. Kyolic aged garlic extract has been shown to reduce arterial stiffness, while normalizing blood pressure, cholesterol and blood thickness. The present study hypothesized that increased flexibility of arteries could lead to slower blood flow and increased oxygen uptake and overall aerobic fitness. The present 12 week trial aimed to assess the effect of Kyolic aged garlic extract (AGE) on arterial stiffness, aerobic fitness, lactate threshold, recovery from muscle soreness and cardiovascular proteomic biomarkers in middle-aged (40-65 years) endurance athletes with elevated arterial stiffness. A total of 75 middle-aged recreational endurance athletes completed the trial, after being randomly allocated for 12 weeks to either the placebo or Kyolic aged garlic extract groups: low-dose cohort 1 (n=37), 2 capsules/day containing 1.2 g AGE powder and 1.2 mg S-allylcysteine (SAC); and the high-dose cohort 2 (n=38), 4 capsules/day of 2.4 g AGE powder and 2.4 mg SAC. Arterial stiffness was assessed through pulse wave velocity measurements and aerobic fitness was measured by volume-maximal-oxygen-consumption (VO2max) and lactate thresholds during high-intensity exercise using a cycle-ergometer-test-station, as well as measuring the levels of muscle fatigue and recovery time at 12 weeks compared with the baseline results. Urinary proteomic analysis was performed in a subgroup of participants and measured the levels of certain relevant proteins used as biomarkers for risk of cardiovascular events, at 12 weeks compared with baseline results. The Kyolic aged garlic extract group significantly improved their aerobic fitness, as was evidenced by increased VO2max, increased aerobic power, higher lactate threshold-to-oxygen uptake, higher lactate threshold-to-power output and quicker recovery times compared with the placebo group. Pulse wave velocity, a measure for arterial flexibility, was improved in the Kyolic aged garlic extract group compared with the placebo. The proteomics analysis demonstrated that a subset of polypeptides associated with cardiovascular risk, such as heart attacks and stroke, decreased in the Kyolic aged garlic extract group at 12 weeks compared with the baseline, which was contrary to the effects observed in the placebo group. Therefore, the results of the present study suggested that Kyolic aged garlic extract significantly improved aerobic fitness, lactate threshold, recovery and cardiovascular proteomic biomarkers in middle-aged endurance athletes within 12 weeks. The present clinical trial was registered on 11/03/2020 at the Australian New Zealand Clinical Trial Registry (trial registration no. ACTRN12620000340932).

Introduction: Colorectal cancer is the third most common cancer worldwide, with 25% of patients being diagnosed with metastatic disease, mostly in the liver, resulting in poor survival. Standard treatment of stage-IV colorectal cancer consists of primary tumour resection followed by chemotherapy. Case Presentation: Here, we report on the treatment effectiveness using integrative therapies in a 52-year-old male with metastatic colon cancer and liver lesions to achieve stable partial remission with an overall high level of wellbeing. After surgical removal of the primary tumour, the 8-month integrative treatment regime consisted of standard anti-angiogenesis treatment, as well as multiple non-standard but evidence-based therapies, including high-dose intravenous nutrients and herbal therapies, oral intake of repurposed medication and nutritional supplements, and a 4-month targeted electromagnetic field/Rife frequency therapy. Conclusion: The integrative therapies used in this case study were highly tolerable and effective in the treatment of metastatic colon cancer with liver lesions, achieving substantial tumour response and stable partial remission with a high level of wellbeing.

Fullerenes (C60s) occur in the environment due to natural and anthropogenic sources such as volcanic eruptions, forest fires, and the combustion of carbon-based materials. Recently, production and application of engineered C60s have also rapidly increased in diverse industrial fields and biomedicine due to C60′ unique physico-chemical properties, so toxicity assessment on environmental and human health is being evaluated as a valuable work. However, data related to the toxicity of C60s have not been abundant up to now. In this study, we studied the immunotoxic mechanism and change of gene expression caused by the instillation of C60s. As a result, C60s induced an increase in sub G1 and G1 arrest in BAL cells, an increase in pro-inflammatory cytokines such as IL-1, TNF-α, and IL-6, and an increase of Th1 cytokines such as IL-12 and IFN-r in BAL fluid. In addition, IgE reached the maximum at 1 day after treatment in both BAL fluid and the blood, and decreased in a time-dependent manner. Gene expression of the MHC class II (H2-Eb1) molecule was stronger than that of the MHC class I (H2-T23), and an increase in T cell distribution was also observed during the experiment period. Furthermore, cell infiltration and expression of tissue damage related genes in lung tissue were constantly observed during the experiment period. Based on this, C60s may induce inflammatory responses in the lung of mice.

Given the rise in worldwide chronic diseases, supplemented by an aging population, the volume of global major surgeries, encompassing cardiac and orthopedic procedures is anticipated to surge significantly. Surgical trauma can be accompanied by numerous postoperative complications and metabolic changes. The present review summarized the results from studies assessing the effects of orthopedic and cardiovascular surgery on vitamin concentrations, in addition to exploring the possible mechanisms associated with changes in concentrations. Studies have revealed a potentially severe depletion in plasma/serum concentrations of numerous vitamins following these surgeries acutely. Vitamins C, D and B1 appear particularly vulnerable to significant depletions, with vitamin C and D depletions consistently transpiring into inadequate and deficient concentrations, respectively. The possible multifactorial mechanisms impacting postoperative vitamin concentrations include changes in hemodilution and vitamin utilization, redistribution, circulatory transport and absorption. For a majority of vitamins, there has been a lack of investigation into the effects of both, cardiac and orthopedic surgery. Additionally, studies were predominantly restricted to short-term postoperative investigations, primarily performed within the first postoperative week of surgery. Overall, results indicated that further examination is necessary to determine the severity and clinical significance of the possible depletions in vitamin concentrations that ensue cardiovascular and orthopedic surgery.

Vitamin C (ascorbic acid) is a water-soluble vitamin with an array of biological functions. A number of proposed factors contribute to the vitamin's plasma bioavailability and ability to exert optimal functionality. The aim of this review was to systematically assess plasma vitamin C levels post-surgery compared with pre-surgery/the magnitude and time frame of potential changes in concentration. We searched the PUBMED, SCOPUS, SciSearch and the Cochrane Library databases between 1970 and April 2020 for relevant research papers. Prospective studies, control groups and true placebo groups derived from controlled trials that reported means and standard deviations of plasma vitamin C concentrations pre- and postoperatively were included into the meta-analysis. Data were grouped into short-term (<= 7 d) and long-term (>7 d) postoperative follow-up. Twenty-three of thirty-one studies involving 642 patients included in the systematic review were suitable for meta-analysis. Pooled data from the meta-analysis revealed a mean depletion of plasma vitamin C concentration of -17 center dot 99 mu mol/l (39 % depletion) (CI -22 center dot 81, -13 center dot 17) (trial arms = 25, n 565, P < 0 center dot 001) during the first postoperative week and -18 center dot 80 mu mol/l (21 % depletion) (CI -25 center dot 04, -12 center dot 56) (trial arms = 6, n 166, P < 0 center dot 001) 2-3 months postoperatively. Subgroup analyses revealed that these depletions occurred following different types of surgery; however, high heterogeneity was observed amongst trials assessing concentration change during the first postoperative week. Overall, our results warrant larger, long-term investigations of changes in postoperative plasma vitamin C concentrations and their potential effects on clinical symptomology.

Abstract Background Vitamin C (ascorbic acid) is a micronutrient imperative for many bodily functions, with research revealing its functional support of leukocytes. The purpose of this meta-analysis was to determine the effects of surgery on leukocyte vitamin C concentrations by assessing the amount and longevity of post-operative leukocyte vitamin C change. Data Sources We searched the PUBMED, SCOPUS, SciSearch and the Cochrane Library databases for relevant research papers. Studies were included until January 2022, with no time limits. Studies that reported means and standard deviations of leukocyte/buffer layer vitamin C concentrations before and after surgery were included into the meta-analysis. The meta-analysis comprised of eight studies. Results Seven studies (which included 8 individual studies) were included into our meta-analysis. Combined data from the meta-analysis displayed a significant depletion in mean leukocyte vitamin C concentrations during the first 24 hours following the surgery by a mean of 5.37 µg/108 (32.3%) (CI = -6.35, -4.40) (n = 6, p < 0.001) and during the first post-operative week by 4.43 µg/108 (23%) (-7.27, -1.58) (n = 7, p < 0.001). However, this depletion was followed by an uprise in mean ascorbic acid leukocyte concentrations of 0.93 µg/108 (4.8%) (-0.79, 2.66) (n = 6, p = 0.29) at 7 days (or beyond) post-operatively. Conclusion Significant post-operative leukocyte vitamin C depletions were particularly observed during the first post-operative week. Further research is required to validate the observed results and to determine whether the observed depletions may be linked to compromised immunological function and pathophysiologies that arise during the post-operative period.

A significant proportion of cancer patients use forms of complementary medicine or therapies. An integrative approach to cancer management combines conventional medicine with evidence-based complementary medicines/therapies and lifestyle interventions, for the treatment and prevention of disease and the optimisation of health. Its basis is a holistic one; to treat the whole person, not just the disease. It makes use of adjunct technologies which may assist the clinician in diagnosis of early carcinogenesis and monitoring of treatment effectiveness. Many factors contribute to the development of cancer including some which are largely modifiable by the patient and which oncologists may be in a position to advise on, such as stress, poor nutrition, lack of physical activity, poor sleep, and Vitamin D deficiency. An integrative approach to addressing these factors may contribute to better overall health of the patient and better outcomes. Evidence-based complementary medicine approaches include the use of supplements, herbal medicine, various practices that reduce stress, and physical therapies. Individualised to the patient, these can also help address the symptoms and signs associated with cancer and its orthodox treatment.

Background Seasonal-allergic-rhinitis (hay fever) affects approximately 4.6 million (20%) Australians each year. Hay fever manifests as runny/blocked nose and often itchy/sore/swollen eyes, with symptoms greatly impacting the quality of life. Rescue medications such as antihistamines are often needed to restore function, but they may trigger some other unwanted side effects. Probiotics have shown promise to reduce hay fever symptoms. Objective In this randomized double-blind placebo-controlled 12-week trial, we aimed to assess the tolerability and efficacy of the probiotic formula “NC-Seasonal-Biotic” on symptoms, quality-of-life, and immunological and microbial factors. Methods Adults, who had previously suffered from hay fever symptoms, were screened for eligibility and randomly allocated to probiotic or placebo trial powder. Treatment effectiveness was assessed by questionnaires, daily total-nasal-symptom-score, and weekly rhinoconjunctivitis quality-of-life questionnaire. Secondary outcome measures included immunological parameters such as T-cell immunity (Th1/Th2 ratio) and the stool-microbiome analysis. Tolerability was assessed weekly by the gastrointestinal symptom scale. Results Recruitment and follow-up were challenging around the 2020/2021 hay fever season in Melbourne, Australia, due to the harsh COVID-19 restrictions and extended lockdowns. Out of the 82 adults enrolled in this study, 75% participated (n = 60), and half (n = 40) completed the 10–12-week intervention period. In the intention-to-treat analysis, no significant differences in hay fever symptoms were apparent between the groups, while quality-of-life trended toward greater improvement in the active group. Intention-to-treat analysis was confounded due to a third of all participants not completing the full 10–12-week-intervention period. Subgroup analyses of the participants (n = 40) completing the full 10–12-week study period revealed a significantly greater reduction in symptoms in the active group compared with the placebo group, including runny nose (p = 0.04) and itchy eyes (p = 0.01). Furthermore, the active group reported significant improvements in the quality-of-life, including more functionality during the day (p = 0.05), better sleep (p = 0.005), less fatigue (p = 0.04), less thirst (p = 0.007), and less irritability (p = 0.007). Immunological parameters, measured by T-helper cell ratio (Th1/Th2), improved significantly in the active group compared with the placebo group. Most microbial changes were not statistically different between the groups. The trial powder was generally well tolerated. Conclusion Our study suggests the probiotic formula “NC-Seasonal-Biotic,” taken for 10–12 weeks, as effective in reducing hay fever symptoms, such as runny nose and itchy eyes, and improved the quality-of-life and immunological parameters while being well tolerated. Clinical Trial Registration [www.ClinicalTrials.gov], identifier [ACTRN126200 01078943].

Background COVID-19 is a global pandemic. Treatment with hydroxychloroquine (HCQ), zinc, and azithromycin (AZM), also known as the Zelenko protocol, and treatment with intravenous (IV) vitamin C (IVC) have shown encouraging results in a large number of trials worldwide. In addition, vitamin D levels are an important indicator of the severity of symptoms in patients with COVID-19. Objectives Our multicenter, randomized, open-label study aimed to assess the effectiveness of HCQ, AZM, and zinc with or without IVC in hospitalized patients with COVID-19 in reducing symptom severity and duration and preventing death. Methods Hospitalized patients with COVID-19 in seven participating hospitals in Turkey were screened for eligibility and randomly allocated to receive either HCQ, AZM, and zinc (group 1) or HCQ, AZM, zinc plus IV vitamin C treatment (group 2) for 14 days. The patients also received nontherapeutic levels of vitamin D3. The trial is registered on the Australian and New Zealand Clinical Trial Registry ACTRN12620000557932 and has been approved by the Australian Therapeutic Goods Administration (TGA). Results A total of 237 hospitalized patients with COVID-19 aged 22-99 years (mean: 63.3 ± 15.7 years) were enrolled in the study. Almost all patients were vitamin D deficient (97%), 55% were severely vitamin D deficient (<25 nmol/L) and 42% were vitamin D deficient (<50 nmol/L); 3% had insufficient vitamin D levels (<75 nmol/L), and none had optimal vitamin D levels. Of the patients, 73% had comorbidities, including diabetes (35%), heart disease (36%), and lung disease (34%). All but one patient (99.6%; n = 236/237) treated with HCQ, AZM, and zinc with or without high-dose IV vitamin C (IVC) fully recovered. Additional IVC therapy contributed significantly to a quicker recovery (15 days versus 45 days until discharge; p = 0.0069). Side effects such as diarrhea, nausea, and vomiting, reported by 15%-27% of the patients, were mild to moderate and transient. No cardiac side effects were observed. Low vitamin D levels were significantly correlated with a higher probability of admission to the intensive care unit (ICU) and longer hospital stay. Sadly, one 70-year-old female patient with heart and lung disease died after 17 days in ICU and 22 days in the hospital. Her vitamin D level was 6 nmol/L on admission (i.e., severely deficient). Conclusions Our study suggests that the treatment protocol of HCQ, AZM, and zinc with or without vitamin C is safe and effective in the treatment of COVID-19, with high dose IV vitamin C leading to a significantly quicker recovery. Importantly, our study confirms vitamin D deficiency to be a high-risk factor of severe COVID-19 disease and hospitalization, with 97% of our study’s patient cohort being vitamin D deficient, 55% of these being severely vitamin D deficient, and none had optimal levels. Future trials are warranted to evaluate the treatment with a combination of high-dose vitamin D3 in addition to HCQ, AZM, and zinc and high-dose intravenous vitamin C.

BACKGROUND:Post-operative cognitive function has recently become an area of focus for researchers. The most commonly reported perioperative neurocognitive disorders include delirium and longer-lasting post-operative cognitive dysfunctions. The contributing pathophysiology to these complications remains unclear. A number of studies have systematically revealed a significant post-operative plasma vitamin C depletion. Recent insights have also exhibited a link between plasma vitamin C and numerous biological roles in brain function, with deficiencies potentially compromising cognitive function. AIM:The present prospective, observational study will investigate whether there is a possible link between post-operative plasma vitamin C depletion and cognitive dysfunction. METHODS:The cohort will consist of surgical patients, between the ages of 65 and 85 years, undergoing hip replacement surgery or a control group not exposed to surgical trauma. Participants will have their plasma vitamin C concentrations tested alongside a battery of computer-based cognitive assessments and paper and pen based cognitive tests. Further assessments will include dietary nutritional intake, serum vitamin B12 concentrations, cardiovascular biomarkers, wound healing, sleep quality, pain, mood and inflammatory cytokines. Participants will be tested at baseline (1-2 weeks prior to surgery) and subsequent testing sessions will be performed within 1 week, 4-6 weeks, 3 months and 6 months following surgery. CONCLUSIONS:Findings from this observational study will provide insight into whether there is a concomitant depletion in post-operative plasma vitamin C concentrations and cognition function. Extrapolated results may prompt future, extensive randomized controlled trials to assess whether vitamin C supplementation can alleviate or even prevent post-operative cognitive complications.

There is increasing evidence that sex differences in the brain may contribute to gender-related behavioral differences, including cognitive function. Literature has revealed gender dimorphisms in cognitive function between males and females. Additionally, several risk factors associated with cognitive decline depend on chronological age. It is well recognized that the process of aging is associated with a decline in cognitive ability and brain function. Various explanations may account for these gender-related cognitive differences and age-associated cognitive changes. Recent investigations have highlighted the importance of vitamin C in maintaining brain health and its association with cognitive function in both cognitively intact and impaired cohorts. The present review explores previous literature that has evaluated differences in plasma/brain vitamin C between genders and during aging. It then assesses whether these age and gender-related differences may affect the relationship between plasma/brain vitamin C and cognition. The purpose of this review was to examine the evidence for a link between plasma/brain vitamin C and cognition and the impact of gender and age on this relationship. Epidemiological studies have frequently shown higher vitamin C plasma concentrations in women. Similarly, aging has been systematically associated with reductions in plasma vitamin C levels. A range of animal studies has demonstrated potential gender and age-related differences in vitamin C brain distribution and utilization. The reviewed literature suggests that gender differences in plasma and brain vitamin C may potentially contribute to differences in gender-associated cognitive ability, particularly while females are pre-menopausal. Additionally, we can propose that age-associated differences in plasma and brain vitamin C may be potentially linked to age-associated cognitive differences, with older cohorts appearing more vulnerable to experience declines in plasma vitamin C concentrations alongside compromised vitamin C brain regulation. This review encourages future investigations to take into account both gender and age when assessing the link between plasma vitamin C concentrations and cognitive function. Further large scale investigations are required to assess whether differences in cognitive function between genders and age groups may be causally attributed to plasma vitamin C status and brain distribution and utilization.

Post-operative neurocognitive disorders are becoming well-documented conditions, with their pathogenesis remaining unclear. Vitamin C is a molecule that has recently demonstrated both a potential link with cognitive function and a significant post-operative decline. Here, we present a case study of a 72-year-old male who underwent total knee replacement surgery. The patient demonstrated a substantial decline in plasma vitamin C concentrations, indicative of a severe deficiency, during the first post-operative week (post-operative Days 3 and 7). Similarly, at these time points, a number of validated paper and pen tests revealed a substantial decline in cognition on tasks relating to total recall, delayed recall, motor speed, recognition and motor speed, with no signs of delirium. These results provide the justification for larger, cohort studies to determine whether post-operative plasma vitamin C depletions could contribute to cognitive deficits post-operatively.

Garlic supplements have shown effectiveness in reducing blood pressure in hypertensive patients, similarly to first-line standard anti-hypertensive medications. Kyolic garlic has also shown promise in improving cardiovascular health by reducing arterial stiffness, elevated cholesterol levels and blood 'stickiness'. In addition, the prebiotic properties in garlic increase gut microbial richness and diversity. This article systematically reviews previously published trials investigating the effects of garlic on blood pressure, and provides an updated meta-analysis of hypertensive participants. In addition, we summarise the findings of recent clinical trials investigating the effects of Kyolic aged garlic extract on arterial stiffness, and gut microbiota in hypertensive subjects. We searched online electronic databases, including PubMed and Google Scholar for randomised controlled trials (RCTs) published between 1955 and December, 2018 examining the effects of garlic on high blood pressure. The meta-analysis of 12 trials and 553 hypertensive participants confirmed that garlic supplements lower systolic blood pressure (SBP) by an average of 8.3 +/- 1.9 mmHg and diastolic blood pressure (DBP, n=8 trials, n=374 subjects) by 5.5 +/- 1.9 mmHg, similarly to standard anti-hypertensive medications. This reduction in blood pressure was associated with a 16-40% reduction in the risk of suffering from cardiovascular events. Additionally, this review summarises new evidence for the vitamin B12 status playing an important role in the responsiveness of blood pressure to garlic. Furthermore, Kyolic aged garlic extract significantly lowered central blood pressure, pulse pressure, pulse wave velocity and arterial stiffness, and improved the gut microbiota, evidenced by higher microbial richness and diversity, with a marked increase in the numbers of Lactobacillus and Clostridia species found following 3 months of supplementation. Thus, Kyolic aged garlic extract is considered to be highly tolerable with a high safety profile either as a stand-alone or adjunctive anti-hypertensive treatment, with multiple benefits for cardiovascular health.