Aesthetics Advisor

If a drug has been shown to work in a small study, would you wait for a bigger study or should you just take it after considering the benefit and risk ratio? Large randomised controlled trials are ideal but by the time the trial is complete, peer-reviewed and published, the results are out-dated and are considered 'laggard' indicators. In this day and age, and especially with this globally destructive pandemic, we need to be 'predictive' rather than 'reactive'. Too many lives and livelihoods are at stake.

It's a lot easier to apologize for administering a benign four decade-old medicine like ivermectin for not being effective, than it is to apologize for not administering a medicine due to “lack of high quality evidence” that could have saved millions of lives.

Check out the evidence tracker on vitamin D and COVID-19 from c19vitamind.com (constantly updated), with more than 100 published studies by more than 900 scientists.

Data from 14 observational studies — suggest that vitamin D blood levels are negatively correlated with the incidence and/or severity of COVID-19; meaning if your vitamin D level is high, your risk for COVID-19 is low and vice versa.

Yet another study from Belgium has demonstrated the significance and importance of adequate levels of zinc and selenium in patients who have COVID-19, and especially in those who have underlined comorbidities identified to increase the severity of disease. Check out the evidence tracker on zinc and COVID-19 from c19zinc.com (constantly updated). There are many Zinc studies underway and you can review the status of these trials on clinicaltrials.gov. As of December 2021, there are more than 20 studies that have been launched to investigate the benefits of Zinc against COVID-19.

Interestingly, some researchers have proposed low zinc status may contribute to the loss of smell that sometimes accompanies respiratory viral infections (J Clin Biochem Nutr. 2021 Jan); while one study found no significant relationship between zinc status and loss of smell in 134 patients with a viral respiratory infection, it did note those who received 50 mg elemental zinc twice daily recovered their sense of smell more quickly than those who received no zinc (Abdelmaksoud et al. 2021 Jan).

5. Curcumin and Turmeric - Anti-inflammatory and anti-viral

Curcumin, a yellow carotenoid from turmeric, is well known for its anti-inflammatory and free radical-scavenging effects. 

It has also demonstrated antiviral effects against a range of respiratory viruses, including influenza A virus and others (Ref). Computer models suggest curcumin may interfere with viral entry into cells as well as viral replication inside cells (Ref). Numerous preclinical studies indicate curcumin may activate antiviral immunity; at the same time, curcumin appears to inhibit infection-induced inflammatory signaling and promote anti-inflammatory processes, reducing the potential for a cytokine storm and ARDS and protecting other organ systems (Ref). By suppressing inflammation, curcumin has the potential to help mitigate complications and sequelae of severe acute viral respiratory infections (Ref).

Curcumin also acts as natural zinc ionophores and can promote the cellular uptake of zinc and can be used with zinc to increase the effectiveness of these compounds in the inhibition of the virus (Ref).

Curcumin has been demonstrated (Ref) to suppress several inflammatory cytokines and mediators of their release such as tumor necrosis factor-alpha (TNF-alpha), IL-1, IL-8 and nitric oxide synthase.

In an open-label trial, 21 patients hospitalized with mild-to-moderate illness due to a highly infectious respiratory virus were treated with a nano-curcumin preparation providing 80 mg curcuminoids (curcumin and its related compounds) twice daily for two weeks in conjunction with standard therapies; their progress was compared with 20 similar patients treated with standard therapies alone. Those who received curcumin had better oxygenation status beginning on day two of treatment, as well as faster resolution of most symptoms, faster normalization of immune cell numbers, less likelihood of worsening of their clinical status, shorter time requiring supplemental oxygen, and shorter hospital stays (Ref).

In a double-blind placebo-controlled trial of 40 participants with a viral respiratory illness, those who received 160 mg nano-curcumin per day for 14 days along with standard therapy had greater reductions in some inflammatory cytokines, including IL-6. They also experienced significant improvement in more symptoms and had a lower fatality rate than those receiving placebo (Ref).

The same research group conducted another double-blind placebo-controlled trial in hospitalized patients with the same virulent respiratory virus, 40 with severe illness receiving intensive care and 40 with mild illness; half of the participants in each group received 160 mg nano-curcumin per day for 14 days and the other half received placebo. Curcumin-treated patients had lower numbers and activity of immune cells known to be involved in cytokine storm and hyper-inflammation. They also had greater improvement in fever, cough, and shortness of breath, and had lower mortality rates (0% vs. 5% in those with mild illness and 5% vs. 25% in those with severe illness [p<.0001 for both mild and severe cases]) than those who received placebo (Ref).

One study found that among 26,779 people tested for COVID-19, those who reported using melatonin supplements were less likely to have the disease (PLoS Biol. 2020).

Safety: If you take a melatonin supplement, be careful: Too much can cause daytime sleepiness. There is no federal RDA nor any formal advice on supplement dose ranges. Based on an on-going Spanish study, a 2 mg daily dose protocol is being investigated for prevention of COVID-19. Do take note that the dosage for 'prevention' and 'treatment' is different, For prevention or maintenance, a lower dosage is normally recommended whereas a 'treatment' or 'therapeutic' dosage is normally higher.

Typical doses of 1–10 mg/day melatonin appear to be safe for short-term use (Source). Reported side effects, which are usually minor, include dizziness, headache, nausea, upset stomach, rash, and sleepiness. However, some reports have linked high blood levels of melatonin with delayed puberty and hypogonadism.

Studies have not evaluated melatonin supplementation during pregnancy and breastfeeding, but some research suggests that these supplements might inhibit ovarian function (Source). Therefore, some experts recommend that women who are pregnant or breastfeeding avoid taking melatonin.

10. Probiotics and COVID-19 - Anti-inflammatory

Through the mesenteric lymphatic system, intact bacteria and their metabolites enter the circulation and influence the lung immune response (gut/lung axis). Through this way intestinal metabolites, mainly produced by bacterial fermentation of dietary fiber, such as short-chain fatty acids (SCFAs), significantly influence local gut immunity but also distant organs. SCFAs derived from gut are able to suppress lung inflammation (Ref). Dendritic cells (DCs), the antigen-presenting cells of the immune system, stimulate T-cells subpopulations in mesenteric lymph nodes and gut lymphatic tissue to produce regulatory cytokines. After airways immune-stimulation, these T-cells move from the gut to the respiratory system, providing protection and stimulating an anti-inflammatory response. In fact, gut microbiota rebalancing has been shown to reduce ventilator-associated enteritis and pneumonia (Ref). 

Altered bacterial balance (dysbiosis) causes the translocation of cytokines, endotoxins and microbial metabolites in the general circulation to other organs, such as the lung. Conversely, respiratory inflammation (due to many causes, e.g., respiratory viral infections due to COVID-19 virus), causes local dysbiosis and, in turn, the translocation of microbial metabolites and toxins to other organs, such as the gut (below).

 
Physiological changes in the human microbiota with age leads to a “physiological dysbiosis”, with less diversification in microbial composition, aggravated in case of comorbidity (hypertension, diabetes, chronic inflammatory bowel diseases, etc.) (Ref). Therefore, to establish the condition of eubiosis (healthy condition), “good” bacteria are required. The concept of probiotics as a food with positive effects was firstly used by Parker RB in 1974 and then recognized by the Food and Agriculture Organization (FAO), and more recently by the Word Health Organization (WHO) (Ref).

Multiple randomized controlled trials and several meta-analyses have shown probiotics reduce the risk of acute respiratory tract infections (eg, colds and flu) (Ref).

Recently, several peer-reviewed reports of clinical experiences, preclinical studies, small, open clinical trials, case series, and clinical hypotheses have suggested that certain immune-modulating probiotic strains, such as L. rhamnosus CRL-1505 (Ref), Streptococcus salivarius K12 (Ref), L. plantarum LP01 (Ref), and B. lactis BS01 (Ref) may confer protection against respiratory viral infections and/or subsequent inflammatory sequela. 

The first quadrupled blinded randomised controlled trial (MedRxiv May 2021) on a novel probiotic formulation demonstrated that complete remission on day 30 was boosted from 28% to 53%.

 

Sivomixx®800 is a probiotic formulation containing eight different strains of lactobacilli and bifidobacteria mixed in a specific ratio. Sivomixx®800 has been the object of numerous experimental and clinical studies proving its effectiveness in debilitating diseases such as Alzheimer's, Parkinson's and epilepsy. Researchers at Policlinico Umberto I Hospital, Sapienza University, Rome, Italy, have evaluated Sivomixx®800 supplementation in a controlled trial including 69 adult COVID-19 patients with a confirmed diagnosis of SARS-CoV-2 related pneumonia. All patients in the study had a CT lung involvement of ≥50% and required non-invasive oxygen therapy (Ceccarelli et al., 2021). 

 

Patients supplemented with Sivomixx®800 were administered three sachets of Sivomixx®800 (800 billion CFU per dose; total 2.400 billion CFU per day) daily, in addition to routine pharmacological therapy for COVID-19. The subjects treated with Sivomixx®800 experienced a significant improvement in blood oxygenation parameters. This change was evident within a few hours from the first administration of Sivomixx®800. Of note, the patients on standard therapy without the addition of the probiotic required substantially higher oxygen requirements and had a higher probability of being transferred to the intensive care unit (2.5% in the probiotic group vs 13.8% in the control group). 

 

Previously, the same research team (d'Ettorre et al., 2020; Ceccarelli et al., 2021) observed that patients showed a higher chance of survival and a reduced risk of respiratory failure when administered Sivomixx®800. This unique, patented formulation modulates oxygen consumption at the intestinal level and, therefore, facilitates adequate oxygenation to other critical organs such as the brain, heart and liver. The “oxygen sparing effect” of Sivomixx®800 marks the way in opening a new therapeutic scenario where Sivomixx®800 is a safe add-on to the standard of care drugs for a broad spectrum of debilitating hypoxia-related diseases such as chronic fatigue, neurodegenerative disorders, neonatal hypoxia, and myocardial ischaemia.

11. B Vitamins and COVID-19 - Anti-inflammatory

Thiamine, at 200 mg twice daily, reduced mortality in patients with septic shock and thiamine deficiency, and laboratory research suggests it may inhibit the hyper-inflammatory immune response that accompanies cytokine storm (Ref). It is a key therapeutic in the MATH+ protocol (methylprednisolone, ascorbic acid [vitamin C], thiamine, and heparin, plus other supportive nutrients and medications), a treatment strategy proposed for managing advanced stages of severe acute viral respiratory illness (Ref). Although high-quality clinical evidence is lacking, two US hospitals implementing the MATH+ protocol in patients with a severe acute viral respiratory illness reported mortality rates that were approximately one-quarter of those reported from other US hospitals using standard care (Ref).

In a study in Saudi Arabia (Al Sulaiman et al. Crit Care 2021), 738 critically ill COVID-19 patients from two centers were included in the study. The in-hospital death rate and 30-day death rate were significantly lower in the group that received thiamine as an adjunctive treatment (a therapy given in addition to standard therapy). In addition, the thiamine group also were less likely to have blood clot during ICU stay.

Another study of COVID-19 patients with severe symptoms found 26.3% among diabetics with COVID-19 were vitamin B1 deficient.