Efficacy of Adaptogens in Patients with Long COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial

Abstract:

Currently, no effective treatment of comorbid complications or COVID-19 long-haulers during convalescence is known. This randomized, quadruple-blind, placebo-controlled trial aimed to assess the efficacy of adaptogens on the recovery of patients with Long COVID symptoms. One hundred patients with confirmed positive SARS-CoV-2 test, discharged from COVID Hotel isolation, Intensive Care Unit (ICU), or Online Clinics, and who experienced at least three of nine Long COVID symptoms (fatigue, headache, respiratory insufficiency, cognitive performance, mood disorders, loss of smell, taste, and hair, sweatiness, cough, pain in joints, muscles, and chest) in the 30 days before randomization were included in the study of the efficacy of Chisan®/ADAPT-232 (a fixed combination of adaptogens Rhodiola, Eleutherococcus, and Schisandra) supplementation for two weeks.

Chisan® decreased the duration of fatigue and pain for one and two days, respectively, in 50% of patients. The number of patients with lack of fatigue and pain symptoms was significantly less in the Chisan® treatment group than in the placebo group on Days 9 (39% vs. 57%, pain relief, p = 0.0019) and 11 (28% vs. 43%, relief of fatigue, * p = 0.0157). Significant relief of severity of all Long COVID symptoms over the time of treatment and the follow-up period was observed in both groups of patients, notably decreasing the level of anxiety and depression from mild and moderate to normal, as well as increasing cognitive performance in patients in the d2 test for attention and increasing their physical activity and workout (daily walk time).

However, the significant difference between placebo and Chisan® treatment was observed only with a workout (daily walk time) and relieving respiratory insufficiency (cough). A clinical assessment of blood markers of the inflammatory response (C-reactive protein) and blood coagulation (D-dimer) did not reveal any significant difference over time between treatment groups except significantly lower IL-6 in the Chisan® treatment group. Furthermore, a significant difference between the placebo and Chisan® treatment was observed for creatinine: Chisan® significantly decreased blood creatinine compared to the placebo, suggesting prevention of renal failure progression in Long COVID. In this study, we, for the first time, demonstrate that adaptogens can increase physical performance in Long COVID and reduce the duration of fatigue and chronic pain. It also suggests that Chisan®/ADAPT-232 might be useful for preventing the progression of renal failure associated with increasing creatinine.

Source: Karosanidze I, Kiladze U, Kirtadze N, Giorgadze M, Amashukeli N, Parulava N, Iluridze N, Kikabidze N, Gudavadze N, Gelashvili L, Koberidze V, Gigashvili E, Jajanidze N, Latsabidze N, Mamageishvili N, Shengelia R, Hovhannisyan A, Panossian A. Efficacy of Adaptogens in Patients with Long COVID-19: A Randomized, Quadruple-Blind, Placebo-Controlled Trial. Pharmaceuticals (Basel). 2022 Mar 11;15(3):345. doi: 10.3390/ph15030345. PMID: 35337143; PMCID: PMC8953947. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953947/ (Full text)

The Role of Nutrients in Prevention, Treatment and Post-Coronavirus Disease-2019 (COVID-19)

Abstract:

SARS-CoV-2 virus, infecting human cells via its spike protein, causes Coronavirus disease 2019 (COVID-19). COVID-19 is characterized by shortness of breath, fever, and pneumonia and is sometimes fatal. Unfortunately, to date, there is still no definite therapy to treat COVID-19. Therefore, the World Health Organization (WHO) approved only supportive care. During the COVID-19 pandemic, the need to maintain a correct intake of nutrients to support very weakened patients in overcoming disease arose. The literature available on nutrient intake for COVID-19 is mainly focused on prevention. However, the safe intake of micro- and/or macro-nutrients can be useful either for preventing infection and supporting the immune response during COVID-19, as well as in the post-acute phase, i.e., “long COVID”, that is sometimes characterized by the onset of various long lasting and disabling symptoms. The aim of this review is to focus on the role of nutrient intake during all the different phases of the disease, including prevention, the acute phase, and finally long COVID.

Source: Motti ML, Tafuri D, Donini L, Masucci MT, De Falco V, Mazzeo F. The Role of Nutrients in Prevention, Treatment and Post-Coronavirus Disease-2019 (COVID-19). Nutrients. 2022 Feb 26;14(5):1000. doi: 10.3390/nu14051000. PMID: 35267974; PMCID: PMC8912782. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912782/ (Full text)

Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review

Abstract:

Creatine monohydrate (CrM) is one of the most widely used nutritional supplements among active individuals and athletes to improve high-intensity exercise performance and training adaptations. However, research suggests that CrM supplementation may also serve as a therapeutic tool in the management of some chronic and traumatic diseases. Creatine supplementation has been reported to improve high-energy phosphate availability as well as have antioxidative, neuroprotective, anti-lactatic, and calcium-homoeostatic effects. These characteristics may have a direct impact on mitochondrion’s survival and health particularly during stressful conditions such as ischemia and injury.

This narrative review discusses current scientific evidence for use or supplemental CrM as a therapeutic agent during conditions associated with mitochondrial dysfunction. Based on this analysis, it appears that CrM supplementation may have a role in improving cellular bioenergetics in several mitochondrial dysfunction-related diseases, ischemic conditions, and injury pathology and thereby could provide therapeutic benefit in the management of these conditions. However, larger clinical trials are needed to explore these potential therapeutic applications before definitive conclusions can be drawn.

Source: Marshall RP, Droste JN, Giessing J, Kreider RB. Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review. Nutrients. 2022 Jan 26;14(3):529. doi: 10.3390/nu14030529. PMID: 35276888. https://www.mdpi.com/2072-6643/14/3/529/htm (Full text)

Does Dietary Coenzyme Q10 plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a neuroinflammatory, multifaceted chronic disorder of unknown cause. Accumulating data indicates a link between a redox imbalance, mitochondrial dysfunction, and inflammation status in ME/CFS. CoQ10 and selenium as effective antioxidant and anti-inflammatory agents have shown potential clinical implications in chronic diseases; however, their therapeutic benefits on ME/CFS remain elusive.

This open-label exploratory study aimed to evaluate the effectiveness of combined CoQ10 plus selenium supplementation on clinical features and circulating biomarkers in ME/CFS. Twenty-seven ME/CFS patients received an oral combination of 400 mg of CoQ10 and 200 µg of selenium daily for 8-weeks. The primary endpoint was patient-reported changes in outcome measures from baseline to 8 weeks post-intervention.

Secondary endpoint included changes in circulating biomarkers from baseline to each participant. After an 8-week intervention, a significant improvement was found for overall fatigue severity (p = 0.021) and global quality of life (p = 0.002), while there was no significant effect on the sleep disturbances (p = 0.480) among participants. After 8-weeks’ intervention, there was significantly increased total antioxidant capacity, and there were reduced lipoperoxides levels from the participants (p < 0.0001 for both). Circulating cytokine levels decreased significantly (p < 0.01 for all), but with no significant changes on the CRP, FGF21, and NT-proBNP biomarkers after supplementation.

Based on these findings, we hypothesized that long-term supplementation of combined CoQ10 and selenium may indicate a potentially beneficial synergistic effect in ME/CFS.

Source: Castro-Marrero J, Domingo JC, Cordobilla B, Ferrer R, Giralt M, Sanmartin-Sentañes R, Alegre-Martin J. Does Dietary Coenzyme Q10 plus Selenium Supplementation Ameliorate Clinical Outcomes by Modulating Oxidative Stress and Inflammation in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Antioxid Redox Signal. 2022 Mar 1. doi: 10.1089/ars.2022.0018. Epub ahead of print. PMID: 35229657. https://pubmed.ncbi.nlm.nih.gov/35229657/

Ginseng for the Treatment of Chronic Fatigue Syndrome: A Systematic Review of Clinical Studies

Abstract:

Background: Chronic fatigue syndrome (CFS) is a complex and often disabling chronic condition emerging worldwide, with no curative or definitive therapy yet identified. Ginseng has been widely used to treat fatigue in other patient groups and conditions; however, a systematic review focusing solely on the impact of ginseng on fatigue in patients with CFS has not been performed.

Objective: This study aimed to assess the current state of evidence regarding ginseng for CFS.

Methods: Multiple databases were searched from inception to October 2020. All data was extracted independently and in duplicates. Outcomes of interest included the effectiveness and safety of ginseng in patients with CFS.

Results: 2 studies enrolling 68 patients were deemed eligible, including one randomized clinical trial and one prospective observational study. The certainty of evidence in the effectiveness outcome was low and moderate from both studies, while the safety evidence was very low as reported from one study.

Conclusion: Study findings highlight a potential benefit of ginseng therapy in the treatment of CFS. However, we are not able to draw firm conclusions due to limited clinical studies. The paucity of data warrants limited confidence. There is a need for future rigorous studies to provide further evidence.

Source: Yang J, Shin KM, Abu Dabrh AM, Bierle DM, Zhou X, Bauer BA, Mohabbat AB. Ginseng for the Treatment of Chronic Fatigue Syndrome: A Systematic Review of Clinical Studies. Glob Adv Health Med. 2022 Feb 14;11:2164957X221079790. doi: 10.1177/2164957X221079790. PMID: 35186446; PMCID: PMC8848096. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848096/ (Full text)

Hydrogen water as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome: a pilot randomized trial

Abstract:

Background: Given the absence of effective medical treatments for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), the testing of a new intervention that may ameliorate potentially pathologic levels of oxidative stress, sympathetic arousal, and inflammation may yield symptomatic improvements.

Objective: To explore in a pilot study, the possible beneficial effect of molecular hydrogen (H2) for the symptoms and functional limitations of ME/CFS.

Methods: Twenty-three subjects were randomized to H2 or active placebo which involved drinking up to five glasses daily of hydrogen-enriched water or placebo water for 28 days. Assessments included: (i) self-report fatigue, physical function, and stress; (ii) salivary C-Reactive Protein (inflammation), Uric Acid (antioxidant status), and Alpha-Amylase (sympathetic function); and (iii) heart rate variability (parasympathetic activity). Data were analysed with Wilcoxon rank-sum tests.

Results: Completion rate for the primary outcome measure of fatigue severity was 100% for the 11 hydrogen participants and 91.7% (n = 11) for placebo participants. No significant changes were found on self-report or biological variables in the active vs. placebo treatment conditions. A small, but significant reduction in fatigue was found in the placebo condition. Adverse effects led to treatment discontinuation in 27.2% of H2 subjects. All severe- and moderate-intensity effects were found in the active treatment condition. Adverse effects were not significantly associated with any demographic or symptom variable.

Conclusions: Therapeutic molecular hydrogen did not yield improvement on any biological or symptom measure in individuals with ME/CFS. Dosage reduction might benefit any future trial of hydrogen therapy in this illness.

Source: Fred Friedberg & Dennis Choi (2022) Hydrogen water as a treatment for myalgic encephalomyelitis/chronic fatigue syndrome: a pilot randomized trial, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2022.2038519

Treatment of chronic fatigue syndrome from yangming meridian

Abstract:

Based on the theory of “brain-gut communication” and “heart-stomach disease simultaneously”, the thinking and method of treating chronic fatigue syndrome (CFS) from yangming meridian were discussed. CFS is related to brain and heart. Based on the analysis of meridian circulation, zangfu function and the indication characteristics of yangming meridian, the indications of yangming meridian are closely related to brain and heart, so it is proposed to start from yangming meridian and use Chinese herbs combined with acupuncture to treat CFS, including the four methods of clearing away heat and moisturizing dryness, cooling blood and removing blood stasis, promoting qi to clear the organs, and strengthening and replenishing deficiency. It has certain guiding and reference significance for clinical treatment of CFS.

Source: Xue KY, Cui J. [Treatment of chronic fatigue syndrome from yangming meridian]. Zhongguo Zhen Jiu. 2022 Feb 12;42(2):203-7. Chinese. doi: 10.13703/j.0255-2930.20210106-0001. PMID: 35152588. https://pubmed.ncbi.nlm.nih.gov/35152588/

Role of Gut Microbiota and Probiotic in Chronic Fatigue Syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a combination of complex illness characterized by tiredness or intense fatigue that may worsen with too much exertion. Among the wide range of neuropsychological symptoms, 97% CFS patients have been reported with neuronal disorders such as headaches and symptoms in the emotional realm.

Patients with CFS also show noticeable alterations in microflora, lowering level of  Lactobacilli and Bifidobacterium.

Recent researches explain that probiotics in the gastrointestinal tract (GIT) can greatly influence the neuronal pathways and central nervous system (CNS) to modulate behavior.

Various studies expressed the benefit of probiotic therapy in normalizing fatigue patients and also restored mitochondrial electron transport function in patients with CFS.

In this chapter, we provided a historical skeleton, bidirectional communication pathophysiology, selection criteria of probiotics, CFS treatment, and clinical implications of gut–brain connections. In summary, various aspects concerning the potential and safety of probiotics in the management of chronic fatigue syndrome are discussed in this chapter.

Source: Sharma A., Wakode S., Sharma S., Fayaz F. (2022) Role of Gut Microbiota and Probiotic in Chronic Fatigue Syndrome. In: Kaur I.P., Deol P.K., Sandhu S.K. (eds) Probiotic Research in Therapeutics. Springer, Singapore. https://doi.org/10.1007/978-981-16-6760-2_9 

Trigger point injections and dry needling can be effective in treating long COVID syndrome-related myalgia: a case report

Abstract:

Introduction: Myofascial pain is a complex health condition that affects the majority of the general population. Myalgia has been recognized as a symptom of long COVID syndrome. The treatment for long COVID syndrome-related myalgia lacks research. Dry needling is a technique that involves the insertion of a needle into the tissue of, or overlaying, a pain point. Wet needling is the addition of an injection of an analgesic substance such as lidocaine while performing needling. Both dry and wet needling have are practiced as treatment modalities for myofascial pain. Limited literature exists to define long COVID syndrome-related myalgia and its relation to myofascial pain, or to examine the utility of needling techniques for this pain. We report a case of dry and wet needling as effective treatments for long COVID-related myofascial pain.

Case presentation: A 59-year-old, previously healthy Hispanic male with no comorbid conditions was diagnosed with COVID-19 pneumonia. The patient suffered moderate disease without hypoxia and was never hospitalized. Three months later, the patient continued to suffer from symptoms such as exertional dyspnea, “brain fog,” and myalgia. An extensive multisystem workup revealed normal cardiac, pulmonary, and end organ functions. The patient was then diagnosed with long COVID syndrome. The nature and chronicity of the patient’s myalgia meet the criteria for myofascial pain. Both wet and dry needling were used to treat the patient’s myofascial pain, with good short- and long-term therapeutic effects.

Conclusions: COVID-19 infection has been shown to exacerbate preexisting myofascial pain syndrome. Our case report indicates that long COVID syndrome-related myalgia is likely a form of new-onset myofascial pain. Additionally, both wet and dry needling can be utilized as an effective treatment modality for this pain syndrome, with short- and long-term benefits.

Source: Zha M, Chaffee K, Alsarraj J. Trigger point injections and dry needling can be effective in treating long COVID syndrome-related myalgia: a case report. J Med Case Rep. 2022 Jan 17;16(1):31. doi: 10.1186/s13256-021-03239-w. PMID: 35039086; PMCID: PMC8763132. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763132/ (Full text)

“LONG COVID”-A hypothesis for understanding the biological basis and pharmacological treatment strategy

Abstract:

Infection of humans with SARS-CoV-2 virus causes a disease known colloquially as “COVID-19” with symptoms ranging from asymptomatic to severe pneumonia. Initial pathology is due to the virus binding to the ACE-2 protein on endothelial cells lining blood vessels and entering these cells in order to replicate. Viral replication causes oxidative stress due to elevated levels of reactive oxygen species. Many (~60%) of the infected people appear to have eliminated the virus from their body after 28 days and resume normal activity. However, a significant proportion (~40%) experience a variety of symptoms (loss of smell and/or taste, fatigue, cough, aching pain, “brain fog,” insomnia, shortness of breath, and tachycardia) after 12 weeks and are diagnosed with a syndrome named “LONG COVID.”

Longitudinal clinical studies in a group of subjects who were infected with SARS-CoV-2 have been compared to a non-infected matched group of subjects. A cohort of infected subjects can be identified by a battery of cytokine markers to have persistent, low level grade of inflammation and often self-report two or more troubling symptoms. There is no drug that will relieve their symptoms effectively.

It is hypothesized that drugs that activate the intracellular transcription factor, nuclear factor erythroid-derived 2-like 2 (NRF2) may increase the expression of enzymes to synthesize the intracellular antioxidant, glutathione that will quench free radicals causing oxidative stress. The hormone melatonin has been identified as an activator of NRF2 and a relatively safe chemical for most people to ingest chronically. Thus, it is an option for consideration of re-purposing studies in “LONG COVID” subjects experiencing insomnia, depression, fatigue, and “brain fog” but not tachycardia. Appropriately designed clinical trials are required to evaluate melatonin.

Source: Jarrott B, Head R, Pringle KG, Lumbers ER, Martin JH. “LONG COVID”-A hypothesis for understanding the biological basis and pharmacological treatment strategy. Pharmacol Res Perspect. 2022 Feb;10(1):e00911. doi: 10.1002/prp2.911. PMID: 35029046. https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.911 (Full text)