In a systematic review and meta-analysis of studies on laughter yoga, researchers suggest that “simulated” (nonhumorous) laughter is more effective than “spontaneous” (humorous) laughter, and that laughter-inducing therapies can improve depressive symptoms.[1] They noticed that significant medium-large effects were observed in two studies over the short term. However, researchers highlight the need to conduct rigorous trials of laughter yoga before the intervention can be considered as an evidence-based intervention to improve mental health.[2]

In a randomized, controlled clinical trial, 60 participants diagnosed with IBS and symptoms of anxiety were randomly assigned to either a laughter yoga group, an antianxiety medication group, or a symptomatic treatment (control) group.[3] Researchers found that anxiety after interventions decreased in all three groups, and especially in the yoga treatment group, but with no statistical significance between groups (p = 0.1). However, the laughter-yoga group experienced a statistically significant decrease in the severity of IBS symptoms than both the anxiety medication and control groups (p = 0.006). Authors concluded that laughter yoga is more effective than antianxiety medication in reducing the gastrointestinal symptoms of patients with IBS, and that applying laughter yoga along with standard treatments for patients with IBS might be strongly advised.[4]

Anthocyanins are bioflavonoids with antioxidant activity. A meta-analysis aimed to determine the effects of anthocyanins on markers of systemic and vascular inflammation in adults > 18 years old.[1] It included 32 randomized, controlled trials from five electronic databases. It found that intake of anthocyanins significantly decreased levels of C‑reactive protein (CRP; p = 0.003), interleukin‑6 (IL‑6; p = 0.004), tumor necrosis factor‑alpha (TNF‑α; p = 0.023), intercellular adhesion molecule‑1 (p = 0.002), and vascular adhesion molecule‑1 (VCAM‑1; p < 0.001). Adiponectin levels were found to significantly increase (p = 0.004). Levels of interleukin‑1beta (IL‑1β; p = 0.793) and P‑selectin (p = 0.219) did not increase. Further, the authors determined, through subgroup analysis, that higher doses of anthocyanins were associated with a more significant decrease in CRP, IL‑6, TNF‑α, and VCAM‑1. Overall, the authors concluded that anthocyanins significantly decrease levels of markers for systemic and vascular inflammation.

In a randomized, double-blind controlled trial (1), 60 adults with mild to moderate knee osteoarthritis were administered twice per day after meals capsules of an herbal formulation of turmeric, ginger, and black pepper extracts containing respectively 300 mg of curcumin, 7.5 mg of gingerols, and 3.75 mg of piperine, or a 250 mg capsule of Naproxen twice in the morning and night for 4 weeks. There were no significant differences in the distribution of demographic characteristics nor in food intake. Blood samples were collected before and after the intervention to assess the inflammatory biomarker prostaglandin E2 (PGE2). The results showed that both groups had a significant decrease of 27 pg/mL in PGE2 (p <.001). However, the differences between the Naproxen and herbal formulation groups were not significant (pre: p = .363, post: p = .112, intervention). Overall, the synergistic effect of the three botanicals mediated inflammation similarly to Naproxen and the authors suggest it could be used as a safer alternative to NSAIDs.

This study explored the effects of saffron on rheumatoid arthritis (RA), a systemic autoimmune and inflammatory disease that causes painful swelling in affected parts of the body. 61 women >18 years old were randomized into either an intervention group (100 mg/day of saffron) or placebo. There were no adverse effects reported by the participants. It was found that those in the saffron group had significantly lower tender (p<0.001) and swollen (p<0.001) joints than placebo and baseline levels. Additionally, pain measured via the visual analogue scale (p<0.001), disease activity scores (p<0.001) and Physician Global assessment (p=0.002) were significantly improved in the saffron group compared to placebo. Further, erythrocyte sedimentation rate (p=0.023), and high sensitivity C-reactive protein (p-0.004), which are both inflammatory markers, were reduced after saffron supplementation compared to baseline. No significant differences were found in tumour necrosis alpha, interferon gamma, malondialdehyde or total antioxidant capacity. The authors propose that these findings suggest that saffron could positively improve both subjective and objective outcomes in patients with RA.

A recent study conducted in 2020 by Italian and Swiss scientists and published in the Journal of Alzheimer Disease, confirmed metagenomic data supporting an association between certain intestinal bacterial strains and Alzheimer’s disease (AD). The study also uncovered association between amyloid pathology and gastrointestinal health using markers such as bacterial products like lipopolysaccharide (LPS), but also short-chain fatty acids (SCFAs: acetate, valerate, butyrate), inflammatory mediators, and markers of endothelial dysfunction in AD.

Eighty-nine individuals with cognitive performance ranging from normal to dementia were studied. Amyloid standardized uptake value ratio (SUVR) was positively associated with blood LPS (rho≥0.32, p≤0.006), acetate and valerate (rho≥0.45, p < 0.001), pro-inflammatory cytokines (rho≥0.25, p≤0.012), and biomarkers of endothelial dysfunction (rho≥0.25, p≤0.042). In contrast, it was negatively correlated with butyrate (rho≤–0.42, p≤0.020) and the anti-inflammatory cytokine IL10 (rho≤–0.26, p≤0.009). Endothelial dysfunction was positively associated with pro-inflammatory cytokines, acetate and valerate (rho≥0.25, p≤0.045) and negatively with butyrate and IL10 levels (rho≤–0.25, p≤0.038). The authors suggest a novel association between gut microbiota-related by-product and systemic inflammation with brain amyloidosis via endothelial dysfunction, suggesting that some SCFAs and LPS represent candidate pathophysiologic links between the gut microbiota and AD pathology. Probiotic supplementation, that still needs to be specifically formulated, is considered as a possible prevention in early stages of the AD’s neurodegenerative process.

The acute respiratory distress syndrome (ARDS) is one of the most severe complications of the SARS-Cov-2 viral infection and other lung pathologies or infections. ARDS entails severe inflammation in the lungs resulting in certain parts of the lung being unusable and cause patients to require mechanical ventilation. A meta-analysis and systematic review conducted out of Sherbrooke Hospital in Quebec, Canada and published in 2019 evaluated the clinical effect of omega-3 polyunsaturated fatty acids on gas exchange and clinical outcomes in ARDS patients. 12 RCT’s (n=1280) were included in the study, all patients were in ICU and all studies compared the administration of omega-3 fatty acids to placebo. A significant improvement in the early PaO2-to-FiO2 ratio (PaO2 - arterial pressure of oxygen; an indication of the percent of oxygen that is being carried in the blood / FiO2 - fraction of inspired oxygen;  room air is approximately 21%, this number increases with more severe ARDS) which persisted at days 7 to 8, and a trend in those receiving ω-3 PUFA toward reduced ICU length of stay and duration of mechanical ventilation. An improvement in this ratio would consist of higher PaO2 and lower FiO2 vales. Whereas mortality, hospital length of stay and infectious complications remained unchanged. This research suggests that the implementation of omega-3 fatty acids may be a reasonable strategy to help as an adjuvant in the treatment of patients with ARDS. 

A prospective investigation was conducted on 4923 Japanese patients with type 2 diabetes to determine the impact of consuming green tea and coffee on their overall mortality. Camellia sinensis (green tea) contains various chemicals such as phenolic acids that are antioxidants, anti-inflammatory and anti-bacterial. Similarly, coffee contains numerous bioactive chemicals that also act as antioxidants and anti-inflammatories. After a median of 5.3-year follow-up (with a 99% follow-up rate), researchers found that the consumption of green tea, coffee and a combination of both beverages were associated with reduced all-cause mortality. (values are per day) Just Green tea: –15% for less than 1cup; –27% for 2-3cups; –30% for over 4 cups / Just Coffee: –12% for less than 1 cup; –19% for 1 cup; –41% for over 2 cups / Combo: –51% for 2-3 cups of tea plus 2 or more cups of coffee; –58% for over 4 cups tea plus 1 cup of coffee; –63% for over 4 cups of tea plus 2 or more cups of coffee. Combining both green tea and coffee brought additive effect with a relative risk reduction of mortality greater : the study reports a 63% lower risk of mortality for a combination of 4 or more cups of green tea with 2 or more cups of coffee every day, as compared to 41% reduced mortality when just consuming 2 cups of coffee per day, or 30% when just consuming 4 cups of green tea per day.

This study analyzed the gene expression in bronchoalveolar lavage fluid in the lungs of 9 COVID patients and 40 controls. In COVID-19 patients, the expression of ACE2 was up regulated by 199 fold compared to the controls, while ACE expression was down regulated by 8-fold showing a deregulated renin angiotensin system (RAS). Additionally, the bradykinin pathway was found to be significantly affected by COVID-19 showing up regulation of bradykinin receptors BKB26 and BKB1R by 207 fold and 2945 fold respectively, with additional markers indicating a bradykinin storm. There was significant up regulation of genes involved in hyaluronic acid synthesis in COVID-19 patients, with down regulation of genes responsible for degradation pathways. The combination of the deregulated RAS system, bradykinin storm and increased hyaluronic acid in the lung tissue can lead to vascular permeability and hyaluronic acid build up in the lungs, producing a hydrogel that can impair proper respiration. Vitamin D is mentioned as a potential adjuvant to help reduce renin production and regulate the RAS system. This study highlighted pathways and revealed specific genes that the authors believe should be targeted to develop COVID-19 therapies.

The following narrative review presents evidence of vitamin D supplementation and the potential reduction of risk for influenza and COVID-19 related illness and mortality. Vitamin D deficiency is common and has been linked to acute respiratory distress syndrome (ARDS) severity, a symptom of COVID-19, and increased mortality alongside the presence of chronic disease and advanced age. There are a variety of mechanisms which implicate vitamin D and its role in immune system activation including: lower viral replication via cathelicidin and defensin production, decreasing the cytokine/chemokine storm which interfere with the lining of the pulmonary epithelium potentially leading to pneumonia, and increasing the expression of antioxidant related genes. Authors recommend for people at an elevated risk of influenza and COVID-19 to take 10,000 IU/d of vitamin D3 for a few weeks, followed by 5000 IU/d with the intention of raising serum levels of 25-hydroxyvitamin D above 100–150 nmol/L, and reduce the risk of infection.The following narrative review presents evidence of vitamin D supplementation and the potential reduction of risk for influenza and COVID-19 related illness and mortality. Vitamin D deficiency is common and has been linked to acute respiratory distress syndrome (ARDS) severity, a symptom of COVID-19, and increased mortality alongside the presence of chronic disease and advanced age. There are a variety of mechanisms which implicate vitamin D and its role in immune system activation including: lower viral replication via cathelicidin and defensin production, decreasing the cytokine/chemokine storm which interfere with the lining of the pulmonary epithelium potentially leading to pneumonia, and increasing the expression of antioxidant related genes. Authors recommend for people at an elevated risk of influenza and COVID-19 to take 10,000 IU/d of vitamin D3 for a few weeks, followed by 5000 IU/d with the intention of raising serum levels of 25-hydroxyvitamin D above 100–150 nmol/L, and reduce the risk of infection.

Sambucus nigra (Elderberry) supplements have demonstrated reduced duration of upper respiratory infection symptoms in several randomized double-blind placebo-controlled trials and meta-analyses (1,2,3). In vitro studies demonstrate that plant lectins, specifically mannose-binding lectins, possess antiviral activity against SARS-CoV family of coronaviruses (4,5). The lectin agglutinin I (SNA-If) isolated from the ripe elderberry fruit (Sambucus nigra) is the compound of interest. The proposed mechanism of action of Elderberry fruit on coronavirus activity, based on pre-clinical studies, suggests that lectin constituents inhibit the coronavirus spike protein during entry into human cells at the binding step thereby inhibiting the replication and viral attachment of human coronavirus. This immunological mechanism of the active compounds in Elderberry, and it's demonstrated reduction of symptom duration on influenza and other upper respiratory tract viruses, makes it a promising option in the treatment and prevention of COVID-19. However more rigorous research and human trials are needed (6).  

Premenstrual Syndrome (PMS) is a condition affecting physical, psychological, and behavioral well-being of 80-90% of women in their reproductive years during menstrual cycles. The following study evaluates the efficacy of Iranian Borage, Echium amoenum (EA), in the treatment of PMS for female college students ages 18-35 years old with 28-35 day cycles1. The EA group received 450 mg capsules (150mg of EA standardized extract TID) from day 21 to day 3 of their next menstrual cycle for a period of two consecutive cycles relative to an inert placebo. The severity of PMS was measured using the premenstrual symptoms screening tool (PSST). Statistically significant differences were seen in the EA group (p ≤ 0.001) in the average scores from 35.3 to 16.1 at baseline to 2 months, respectively, compared to placebo (p = 0.09) from 31.0 to 28.3. EA had the greatest impact on providing symptomatic relief for anxiety, tension and tearfulness.

This meta-analysis aimed to reach a better understanding on the efficacy of acupuncture treatment for IBS1. Studies using body, auricular and scalp acupuncture were included in this review, while acupuncture moxibustion was excluded. 41 papers were included for the systematic review and 40 (3,440 participants) for the meta-analysis. The control varied between trials with 8 using sham acupuncture, 23 trials using western medicine and 4 trials using Chinese herbal medicine. When compared to sham acupuncture, there was increased efficacy in the treatment group with significantly improved IBS symptoms (p=0.04), but there was no significant difference between follow-up scores (p=0.22) or quality of life (p=0.35). Compared to western medicine, acupuncture was also shown to have significantly higher efficacy (p<0.00001) and improved follow up scores (p=0.0002). Finally, Chinese medicine including acupuncture versus Chinese medicine alone showed the acupuncture group had better efficacy (p=0.02). Overall, it was determined that acupuncture can be used as an adjunct to western and Chinese medicine to reach a better clinical effect in the treatment of IBS; however, larger trials are needed to solidify these findings.   

Media outlets have highlighted COVID-19 as a unique threat, subjecting individuals to anxiety, panic, stress, and the potential for hysteria, regardless of the virus being a real or perceived threat (1). Compared to general populations, COVID-19 has proven to be more fatal for those with underlying physical illness, serious mental illness, and those in assisted living. Patients institutionalized in a closed psychiatric unit in Korea experienced a higher mortality rate (7%) than the general Korean population (1%). The unit housed 103 patients, to which 102 tested positive to the virus (1). COVID-19 not only poses serious pathophysiological concerns but psychosocial impediments as well. Acute psychological stress is associated with an increase of pro-inflammatory cytokines, such as interleukin (IL)-1ß and IL-6, the same pro-inflammatory cytokines released by COVID-19 (2). Current COVID-19 therapies address symptomatic treatment, however a critical strategy to reduce infection rate and mortality is prevention (1). Studies show that addressing the psychosocial aspect of this virus and increasing psychoneuroimmunity with regular exercise, balanced nutrition, quality sleep, and strong social connection can boost the immune system. Social distancing and wearing masks will help limit pathogen exposure, however, it is imperative that a variety of psychological support systems be implemented to increase individual resilience and immunity.

The microbiome may play an important role in modulating immune system function and new pre-clinical research is suggesting that commensal bacteria of the gut may have an effect in cancer prognosis. Specific bacterial species in combination with immunotherapy has been recently shown to boost the ability of the immune system to recognize and attack cancer cells, specifically in colorectal, melanoma, and bladder cancer cells in a mice-model (1). Three bacterial species, Bifidobacterium pseudolongum, Lactobacillus johnsonii and Olsenella species, significantly enhanced the efficacy of immune checkpoint inhibitors in mice models of cancer. These bacteria have been found to produce the metabolic metabolite inosine. This metabolite enhances the ability of T-cells to detect and attack tumor cells.

The following review discusses an experimental strategy for the co-administration of quercetin and vitamin C for the prophylaxis and treatment of SARS-CoV-2 related illness (1). The current evidence is that vitamin C and quercetin act synergistically by exerting antiviral properties by interfering with factors associated with viral pathogenicity (i.e. entry, replication, assembly and enzymatic activity), and displaying immunomodulatory effects via stimulating interferon production, T-cell and phagocytic activity. The antiviral and immune responses are enhanced by vitamin C’s ability to recycle oxidized quercetin thus reinforcing its therapeutic effects. The authors proposed optimal dosing recommendations specific to the population needs: prophylaxis and mild cases (quercetin 250-500mg BID and vitamin C 500mg BID), and severe cases (quercetin 500mg BID and vitamin C 3gr q6 for 7 days). In conclusion, co-administration of the two safe and inexpensive nutraceuticals is suggested for integrative use in high-risk populations for the prevention and treatment of SARS-CoV-2.