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The Efficacy of Self-Management Strategies for Females with Endometriosis: a Systematic Review.
Mardon, AK, Leake, HB, Hayles, C, Henry, ML, Neumann, PB, Moseley, GL, Chalmers, KJ
Reproductive sciences (Thousand Oaks, Calif.). 2023;30(2):390-407
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Endometriosis is a gynaecological condition with symptoms of pelvic pain, fatigue, and stress. Decreased quality of life, impaired fertility and hinderances to carry out day to day tasks are all associated with endometriosis. Treatment options involve medications and surgery; however, both are associated with poorer outcomes than the initial disease itself. Self-management strategies that the individual can perform themselves, such as lifestyle changes, meditation, and rest have all been used to improve the quality of life of individuals with endometriosis, however their effectiveness has not been determined. This systematic review and meta-analysis aimed to determine the effectiveness of self-management strategies for the management of endometriosis. The study showed that many self-management strategies were no more effective than placebo or hormonal therapies for the management of endometriosis. It was concluded that many self-management strategies were no more effective than hormonal treatment at reducing endometriosis symptoms and the studies that did show a benefit were insufficient to base recommendations on due to poor design. This study could be used by healthcare professionals to understand that currently the research on self-management strategies of endometriosis is poor and whilst some may be of benefit to individuals who cannot or do not want to take hormone therapy, more research is warranted.
Expert Review
Conflicts of interest:
None
Take Home Message:
It is not possible to generalise the findings of this systematic review for the self-management of endometriosis due to the poor quality of evidence. Further studies of higher quality are needed.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Endometriosis is an inflammatory condition where endometrial-like tissue is found outside of the uterus. Diagnosis of endometriosis is made in around 6-10% of females of reproductive age. Endometriosis can adversely affect fertility, psychological well being and quality of life (QoL). Conventional interventions can have side effects and limited effectiveness. The aim of this systematic review (SR) was to evaluate the efficacy of self-management interventions for pain-related symptoms and QoL.
Methods
Fifteen experimental studies were included in this SR. Ten evaluated dietary supplements, three evaluated dietary modifications, one evaluated over-the-counter (OTC) medication, and one evaluated exercise. Outcome measures were self-reported for dysmenorrhoea, dyspareunia, overall pain, non-menstrual pelvic pain, use of medications and QoL.
Results
- Most dietary supplements were no more effective than placebo or frequently recommended medical interventions, at reducing pain-related outcomes.
- Melatonin (one RCT n=30) performed better than placebo for managing dysmenorrhoea and overall pain but not for non-menstrual pelvic pain. PEA-transploydatin (one RCT n=20) performed better than placebo for dysmenorrhoea and non-menstrual pelvic pain but not better than medical intervention.
- Resveratrol (one RCT n=22 & one intervention study n=12) plus the oral contraceptive pill (OCP) was more effective than the OCP alone for managing dysmenorrhoea.
- In one observational study, 75% of participants (n=295) reported a reduction in ‘high’ intensity pain scores following a 12-month gluten-free diet (p- value =<0.005). Similarly, a full dietary modification (one non randomised controlled trial , n=30) found less participants reporting pain at ‘high intensity’ (18%) compared to linseed and calcium oil supplements (41%) and placebo (62%).
- A metal trace element supplement was more effective than placebo for managing overall pain (one RCT p- value<0.001).
- Naproxen (one cross over trial, n=11) performed better than placebo at managing dysmenorrhoea (83% vs 41%, p- value 0.008).
- Hatha yoga (one RCT n=12) was found to be effective at reducing overall pain and improving QoL compared to no yoga (p-value <0.05).
Conclusion
Due to limited, low-quality evidence, high risk of bias and high levels of heterogeneity between studies, it was not possible to generalise the findings of the studies included in this systematic review. Further research of high-quality is needed in order to make self-management recommendations for females with endometriosis.
Notes: The authors reported no conflicts of interest.
Clinical practice applications:
Evidence-based self-management interventions are considered critical for the management of endometriosis. However, the quality of evidence in this SR was considered of poor quality. Further high-quality research is needed in order to be able to make recommendations. Strategies that showed potential benefits included:
- Dietary modifications and a gluten-free diet may be effective for reducing the intensity of pain associated with endometriosis.
- Hatha yoga may be effective at reducing overall pain and supporting psychological wellbeing and QoL.
Considerations for future research:
High quality studies are needed as well as a ‘gold standard’ definition for self-management criteria. Understanding potential barriers to self-management interventions may also be beneficial.
Abstract
Self-management is critical for the care of endometriosis. Females with endometriosis frequently use self-management strategies to manage associated symptoms; however, the efficacy of such strategies is unknown. The aim of this review was to systematically appraise the evidence concerning efficacy of self-management strategies for endometriosis symptoms. Electronic databases, including Medline, Embase, Emcare, Web of Science Core Collection, Scopus, and the Cochrane Central Register of Controlled Trials, were searched from inception to March 2021. We included peer-reviewed experimental studies published in English evaluating the efficacy of self-management strategies in human females laparoscopically diagnosed with endometriosis. Studies underwent screening, data extraction, and risk of bias appraisal (randomised studies: Risk of Bias 2 tool; non-randomised studies: Risk Of Bias In Non-randomized Studies - of Interventions tool). Of the fifteen studies included, 10 evaluated dietary supplements, three evaluated dietary modifications, one evaluated over-the-counter medication, and one evaluated exercise. Most studies had a high-critical risk of bias. Many self-management strategies were not more effective at reducing endometriosis symptoms compared to placebo or hormonal therapies. Where studies suggest efficacy for self-management strategies, no recommendations can be made due to the poor quality and heterogeneity of evidence. High-quality empirical evidence is required to investigate the efficacy of self-management strategies for females with endometriosis.
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Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Jamshidi, P, Farsi, Y, Nariman, Z, Hatamnejad, MR, Mohammadzadeh, B, Akbarialiabad, H, Nasiri, MJ, Sechi, LA
International journal of molecular sciences. 2023;24(19)
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Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder the cause of which is not yet fully elucidated. Probiotics, prebiotics and dietary changes have been shown to mitigate IBS symptoms whilst the results from studies of faecal microbiota transplants (FMT) have been inconsistent. The aim of this systematic review and meta-analysis of double-blind, randomised controlled trials (RCT) was to evaluate the efficacy and safety of FMT in IBS. 7 RCTs with a low risk of bias and no publication bias were included in the meta-analysis. Overall, no statistically significant effect was observed. A subgroup analysis by treatment modality showed that benefits were seen with lower GI administration of a single dose of multiple-donor FMT. Abdominal pain, nausea, diarrhoea and bloating were the most common adverse events, with no severe or critical adverse events reported. The authors call for larger and longer clinical trials to fill existing knowledge gaps.
Abstract
Irritable bowel syndrome (IBS) poses a significant challenge due to its poorly understood pathogenesis, substantial morbidity, and often inadequate treatment outcomes. The role of fecal microbiota transplantation (FMT) in managing IBS symptoms remains inconclusive. This systematic review and meta-analysis aimed to ascertain the effectiveness of FMT in relieving symptoms in IBS patients. A thorough search was executed on PubMed/Medline and Embase databases until 14 June 2023, including all studies on FMT use in IBS patients. We examined the efficiency of FMT in reducing patients' symptoms overall and in particular subgroups, classified by placebo preparation, FMT preparation, frequency, and route of administration. Among 1015 identified studies, seven met the inclusion criteria for the meta-analysis. The overall symptomatology of FMT-treated IBS patients did not significantly differ from the control group (Odds Ratio (OR) = 0.99, 95% Confidence Interval (CI) 0.39-2.5). Multiple doses of FMT compared with non-FMT placebo, or single-donor FMT therapy compared with autologous FMT placebo also showed no significant benefit (OR = 0.32, 95%CI (0.07-1.32), p = 0.11, and OR = 1.67, 95%CI (0.59-4.67), p = 0.32, respectively). However, a single dose of multiple-donor FMT administered via colonoscopy (lower gastrointestinal (GI) administration) significantly improved patient symptoms compared with autologous FMT placebo (OR = 2.54, 95%CI (1.20-5.37), p = 0.01, and OR = 2.2, 95%CI (1.20-4.03), p = 0.01, respectively). The studies included in the analysis showed a low risk of bias and no publication bias. In conclusion, lower GI administration of a single dose of multiple-donor FMT significantly alleviates patient complaints compared with the autologous FMT used as a placebo. The underlying mechanisms need to be better understood, and further experimental studies are desired to fill the current gaps.
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Effects of Probiotics in Adults with Gastroenteritis: A Systematic Review and Meta-Analysis of Clinical Trials.
Mitra, AK, Asala, AF, Malone, S, Mridha, MK
Diseases (Basel, Switzerland). 2023;11(4)
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Gastroenteritis is a major cause of morbidity and mortality globally and symptoms can range from mild to life-threatening. Some studies have suggested benefits of probiotics in the treatment of gastroenteritis in children whilst in adults, results are inconsistent. The aim of this systematic review and meta-analysis was to evaluate the effects of probiotics on acute and chronic gastroenteritis in adults. 35 clinical trials were included in the systematic review and 22 in the meta-analysis. Of these, 23 dealt with inflammatory bowel disease, 5 with pouchitis, 3 with antibiotic-induced diarrhoea, 2 with Helicobacter pylori infection and one each with diverticulitis and acute watery diarrhoea. 27 (77%) of studies showed some benefits of probiotic administration. The meta-analysis of 22 studies did not show a statistically significant benefit of probiotics. Although statistical analysis showed the studies to be homogenous, the authors point out that studies differed widely in aetiologies and probiotics used. A subgroup analysis of 8 studies in patients with ulcerative colitis also showed no benefit. In all studies, probiotics were well tolerated and no adverse side effects were reported. The authors concluded that further research is needed to help identify the most appropriate use of probiotics for the different types of gastroenteritis.
Expert Review
Conflicts of interest:
None
Take Home Message:
- For chronic inflammatory gastroenteritis conditions in adults, probiotics were effective in treating and preventing relapse
- In ulcerative colitis, probiotics were not effective and adverse events outweighed the benefits
- No safety concerns were found for probiotic use in any studies
- Aetiologies, disease severity and duration as well as the type of probiotics used were widely diverse.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
To date, evidence has been mixed for probiotic effectiveness in gastrointestinal syndromes associated with gastroenteritis. The aim of this study was to review current evidence on the effect of probiotics on gastroenteritis in adults.
Methods
This was a systematic review (n=35; total sample size 4577, median 44) and meta-analysis (n=22) of randomised controlled trials. Quality was assessed using CADIMA as per a rating scale (0 to 4) and standards of critical appraisal.
Results
All 35 studies on gastroenteritis included participants with chronic diarrhoea of diverse aetiologies such as IBD, antibiotic-associated, except one which had acute watery diarrhoea.
51% (n=18) of studies assessed the effects of probiotics in the treatment of ulcerative colitis (UC) and Crohn's disease (CD). 60% (n=21) used multiple strains of probiotics while the rest used single strains. Lactobacilli, Bifidobacteria, Escherichia and Streptococcus were the most common and only a few studies administered probiotics with another conventional treatment.
19 studies (55%) rated highly in terms of quality while 15 (43%) scored moderately. The majority (63%) of the 27 studies where probiotics were shown to be effective were of high quality.
Systematic review results:
- 27/53 studies (77%) showed a favourable response after using probiotics (resolution, improvement, remission or no relapse), mostly in patients with IBDs
- 7 studies (20%) found probiotics to be ineffective
- 1 study was inconclusive
- Multiple strain probiotics (VSL #3) was found to be most effective in IBD
- All administered probiotics were well tolerated with no adverse side effects although caution in immunocompromised patients was mentioned in several studies.
The meta-analysis results:
- Overall effectiveness for 22 studies (p=0.37) highlighted there was not enough evidence that the intervention was more protective than controls.
- Probiotics were not effective in UC (p = 0.28), and adverse events caused by probiotics may outweigh the benefits in studies with UC patients.
Conclusion
While benefits of effectiveness were found for probiotic use in gastroenteritis in adults, results from the systematic review and meta-analysis showed a mixed effect.
Clinical practice applications:
- Based on the systematic review, probiotics may be an effective treatment or adjuvant treatment for gastroenteritis but ineffective for around 20% of patients
- It is worth noting that combined therapy with standard treatment showed effective results
- Beneficial effects of probiotics in other key clinical outcomes including disease prevention, relapse, quality of life, morbidity were found
- While the results are interesting it is difficult to apply them in practice as the type of probiotics used were widely different as were the causes, severity and duration of gastroenteritis.
Considerations for future research:
- Further and larger studies would be beneficial to understand the benefits of probiotics in terms of single therapy or in combination with standard treatment particularly for UC, CDs, gastroenteritis not due to viral infection
- Individual-level data instead of aggregated data could give a better idea of effectiveness of probiotics in the future
- In this study aetiologies and the type, dosage, duration of probiotics used were widely diverse therefore systematic reviews and meta-analysis on specific conditions, specific probiotic strains and combinations would be beneficial.
Abstract
Probiotics have been widely used in gastroenteritis due to acute and chronic illnesses. However, evidence supporting the effectiveness of probiotics in different health conditions is inconclusive and conflicting. The aim of this study was to review the existing literature on the effects of probiotics on gastroenteritis among adults. Only original articles on clinical trials that demonstrated the effects of probiotics in adults with gastroenteritis were used for this analysis. Multiple databases, such as PubMed, Google Scholar, MEDLINE and Scopus databases, were searched for the data. The study followed standard procedures for data extraction using a PRISMA flow chart. A quality appraisal of the selected studies was conducted using CADIMA. Finally, a meta-analysis was performed. Thirty-five articles met the selection criteria; of them, probiotics were found effective in the treatment and/or prevention of chronic inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease in 17 (49%), and the treatment of pouchitis in 4 (11.4%), antibiotic-induced diarrhea in 3 (8.6%), Helicobacter pylori infection in 2 (5.7%) and diverticulitis in 1 (2.9%), while the remaining 7 (20%) were ineffective, and 1 study's results were inconclusive. The meta-analysis did not demonstrate any significant protective effects of probiotics. Having a τ2 value of zero and I2 of 6%, the studies were homogeneous and had minimum variances. Further studies are suggested to evaluate the beneficial effects of probiotics in IBDs and other chronic bowel diseases.
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Effect of supplementation with probiotics or synbiotics on cardiovascular risk factors in patients with metabolic syndrome: a systematic review and meta-analysis of randomized clinical trials.
Chen, T, Wang, J, Liu, Z, Gao, F
Frontiers in endocrinology. 2023;14:1282699
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Metabolic syndrome (metS) is characterised by insulin resistance, dyslipidaemia, central obesity and/or high blood pressure and is a significant risk factor for cardiovascular disease and type 2 diabetes mellitus. MetS is associated with an imbalanced microbiome and some but not all studies have shown benefits of supplementation with probiotics. The aim of this systematic review and meta-analysis of randomised controlled trials was to evaluate the effects of pro- or synbiotics on cardiovascular risk factors (body mass index, LDL cholesterol, fasting blood glucose and systolic blood pressure) in patients with metS. 11 studies were included in the review of which 7 were judged to have a low risk of bias, whilst risk of bias was unclear in 4 articles. The meta-analysis found that pro- or synbiotics have a positive effect on body mass index, LDL cholesterol and fasting blood glucose but not on systolic blood pressure. Subgroup analysis of pro- and synbiotics separately also found no effects on systolic blood pressure.
Abstract
PURPOSE The effectiveness of probiotics or synbiotics in adults with metabolic syndromes (MetS) remains controversial, this meta-analysis will further analyze the effects of probiotics or synbiotics on cardiovascular factors in adults with MetS. METHODS We searched Web of Science, PubMed, Embase, Cochrane Library and other databases for randomized controlled trials (RCTs) on the effects of probiotics or synbiotics on MetS in adults up to July 2023, and used RevMan 5.4.0 software for statistical analysis. RESULTS This analysis included eleven RCTs (n = 608 participants), and the results showed that compared with the control group, supplementation with probiotics or synbiotics reduced body mass index (weighted mean difference, WMD = -0.83, 95% CI = [-1.21, -0.44], P <0.0001, n = 9), low-density lipoprotein (LDL-c) (standard mean difference, SMD = -0.24, 95% CI = [-0.41, -0.08], P = 0.004, n = 10), fasting blood glucose (FBG)(SMD = -0.17, 95% CI = [-0.33, -0.01], P = 0.03, n = 11), but had no beneficial effect on systolic blood pressure (SBP) (WMD = 1.24, 95% CI = [-2.06, 4.54], P = 0.46, n = 8) in MetS patients. CONCLUSION Supplementation with probiotics or synbiotics can reduce BMI, LDL-c, FBG in patients with MetS, but our findings did not demonstrate a favorable effect on reducing SBP. Future studies with larger samples and longer intervention periods are needed.
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The right bug in the right place: opportunities for bacterial vaginosis treatment.
Wu, S, Hugerth, LW, Schuppe-Koistinen, I, Du, J
NPJ biofilms and microbiomes. 2022;8(1):34
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The vaginal microbiome is generally dominated by Lactobacilli bacteria. However, variations exist, and in some ethnic groups a dominance of non-Lactobacilli species is more common. Lactobacilli produce various antimicrobial substances which keep growth of other bacteria in check. Bacterial vaginosis (BV) is characterized by a disturbance of the vaginal microbe balance and deficiency of Lactobacilli, giving rise to the overgrowth of certain bacteria, such as Gardnerella, Atopobium, Megasphaera, Prevotella, and Sneathia. In some countries, BV can affect over half of the women. This review discusses the advantages and challenges of the current treatment options for BV and postulates directions for future research. The article examines the use of antibiotics, their effectiveness and difficulties in obtaining long-term remission, their negative impact on the existing vaginal microbiome, the risk of antibiotic resistance and the benefits and challenges of local antibiotic applications. Following this, the authors discussed the use of prebiotics and probiotics, possible reasons why clinical trials in the past showed mixed results, and what strains may be of particular importance in vaginal health, with L. crispatus and L. iners being of particular interest here. Considered are also factors that influence and enhance bacterial colonization. Lastly, the article summarizes some current thinking on Vaginal Microbiome Transplantation, which is the transfer of vaginal microbes and fluids from a healthy donor, what benefits they may have, the associated safety risks and legislative challenges. This review is a comprehensive summary of BV treatment options, their current evidence, efficacy and drawbacks, yielding useful information to consider in the clinical management of BV.
Abstract
Bacterial vaginosis (BV) is a condition in which the vaginal microbiome presents an overgrowth of obligate and facultative anaerobes, which disturbs the vaginal microbiome balance. BV is a common and recurring vaginal infection among women of reproductive age and is associated with adverse health outcomes and a decreased quality of life. The current recommended first-line treatment for BV is antibiotics, despite the high recurrence rate. Live biopharmaceutical products/probiotics and vaginal microbiome transplantation (VMT) have also been tested in clinical trials for BV. In this review, we discuss the advantages and challenges of current BV treatments and interventions. Furthermore, we provide our understanding of why current clinical trials with probiotics have had mixed results, which is mainly due to not administering the correct bacteria to the correct body site. Here, we propose a great opportunity for large clinical trials with probiotic strains isolated from the vaginal tract (e.g., Lactobacillus crispatus) and administered directly into the vagina after pretreatment.
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Dietary supplements in neurological diseases and brain aging.
Naureen, Z, Dhuli, K, Medori, MC, Caruso, P, Manganotti, P, Chiurazzi, P, Bertelli, M
Journal of preventive medicine and hygiene. 2022;63(2 Suppl 3):E174-E188
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The rate of neurodegenerative diseases (ND) is increasing at a concerning rate. The condition is characterized by the progressive decline of neuron function in the brain, eventually leading to cognitive impairment and motorneuron disorders. This process appears to be mediated by the complex interplay of factors. The brain is extremely sensitive to oxidative stress, and oxidative stress and inflammation of the nervous tissue appear to be a common denominator in all neurodegenerative diseases. One of the challenges of ND for prevention as well as treatment and treatment development, is that the initial disease progression usually goes unnoticed, with symptoms only becoming apparent in the more advanced stages when irreversible damage has occurred. Diet quality has a significant impact on brain health and hence can also influence ND development. For example, the Mediterranean diet (MedDiet) has demonstrated many valuable attributes that can reduce ND incidences and improve cognitive function. This review looked at dietary components, natural compounds and medicinal plants that have shown to be beneficial for brain health in ND. The authors discussed the MedDiet followed by a brief review of dietary supplements, including N-acetylcysteine (NAC), phospholipids (Phosphatidylserine, Phosphatidylcholine), Gamma-aminobutyric acid, melatonin, omega-3 fatty acids, neurotropic vitamin B (B1, B6 and B12), S-adenosyl methionine (SAMe), the amino acid tryptophan, magnesium and various polyphenols. Several medicinal plants are reviewed that have demonstrated positive effects on preventing or alleviating neurological diseases. This includes Withania somnifera (Ashwagandha), Baccopa monnieri (Brahmi), Acorus calamus (Calamus) and Hypericum perforatum (St. Johns Wort). The review concluded that many bioactive compounds and plant constituents that can be obtained from a qualitative diet, as well as certain medicinal plants and supplements, can help preserve and promote brain health and prevent the onset of ND. Large clinical trials are needed to assess their suitability for their wider use.
Abstract
A healthy diet shapes a healthy mind. Diet quality has a strong association with brain health. Diet influences the onset and consequences of neurological diseases, and dietary factors may influence mental health at individual and population level. The link between unhealthy diet, impaired cognitive function and neurodegenerative diseases indicates that adopting a healthy diet would ultimately afford prevention and management of neurological diseases and brain aging. Neurodegenerative diseases are of multifactorial origin and result in progressive loss of neuronal function in the brain, leading to cognitive impairment and motoneuron disorders. The so-called Mediterranean diet (MedDiet) with its healthy ingredients rich in antioxidant, anti-inflammatory, immune, neuroprotective, antidepressant, antistress and senolytic activity plays an essential role in the prevention and management of neurological diseases and inhibits cognitive decline in neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. The MedDiet also modulates the gut-brain axis by promoting a diversity of gut microbiota. In view of the importance of diet in neurological diseases management, this review focuses on the dietary components, natural compounds and medicinal plants that have proven beneficial in neurological diseases and for brain health. Among them, polyphenols, omega-3 fatty acids, B vitamins and several ayurvedic herbs have promising beneficial effects.
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COVID-19 and chronic fatigue syndrome: Is the worst yet to come?
Wostyn, P
Medical hypotheses. 2021;146:110469
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A proportion of COVID-19 patients develop post-COVID-19 syndrome, with long-term symptoms such as persistent fatigue, muscle pains, depressive symptoms, and non-restorative sleep, similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this article the author presents his medical hypothesis that, in a subset of patients at least, post-COVID-19 fatigue syndrome may result from damage to olfactory (smell) sensory neurons, which in turn may lead to toxic build-up within the central nervous system (CNS) through congestion of the glymphatic system (the waste clearance system of the CNS). Loss of smell and altered sensation of taste have been reported in 33–80% of COVID-19 patients but the underlying mechanisms are not yet known. Most of these patients regain their sense of smell within 1-3 weeks, suggesting that the virus does not affect the olfactory neurons but their surrounding supporting cells. Some patients, however, do not regain their sense of smell for months which may point to the destruction of neurons. A decrease in olfactory neurons may affect the flow of the cerebrospinal fluid (CSF) in an area important for CSF drainage. This may cause an increase in intracranial pressure (idiopathic intracranial hypertension, IIH) and congestion of the glymphatic system, which have been associated with chronic fatigue syndrome, as well as with headaches and tinnitus, symptoms also commonly seen in COVID-19 patients. The author states that if this hypothesis is confirmed, glymphatic-lymphatic drainage therapies, such as osteopathy, should be recommended as early treatment for patients with post-COVID-19 fatigue syndrome.
Abstract
There has been concern about possible long-term sequelae resembling myalgic encephalomyelitis/chronic fatigue syndrome in COVID-19 patients. Clarifying the mechanisms underlying such a "post-COVID-19 fatigue syndrome" is essential for the development of preventive and early treatment methods for this syndrome. In the present paper, by integrating insights pertaining to the glymphatic system and the nasal cerebrospinal fluid outflow pathway with findings in patients with chronic fatigue syndrome, idiopathic intracranial hypertension, and COVID-19, I provide a coherent conceptual framework for understanding the pathophysiology of post-COVID-19 fatigue syndrome. According to this hypothesis, this syndrome may result from damage to olfactory sensory neurons, causing reduced outflow of cerebrospinal fluid through the cribriform plate, and further leading to congestion of the glymphatic system with subsequent toxic build-up within the central nervous system. I further postulate that patients with post-COVID-19 fatigue syndrome may benefit from cerebrospinal fluid drainage by restoring glymphatic transport and waste removal from the brain. Obviously, further research is required to provide further evidence for the presence of this post-viral syndrome, and to provide additional insight regarding the relative contribution of the glymphatic-lymphatic system to it. Other mechanisms may also be involved. If confirmed, the glymphatic-lymphatic system could represent a target in combating post-COVID-19 fatigue syndrome. Moreover, further research in this area could also provide new insights into the understanding of chronic fatigue syndrome.
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Role of mitochondria, oxidative stress and the response to antioxidants in myalgic encephalomyelitis/chronic fatigue syndrome: A possible approach to SARS-CoV-2 'long-haulers'?
Wood, E, Hall, KH, Tate, W
Chronic diseases and translational medicine. 2021;7(1):14-26
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Cases of chronic fatigue have been reported following recovery from Covid-19, in what is termed ‘Long Covid’, with symptoms likened to that of sufferers from chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (ME). How CFS/ME develop and treatments may help to further understand Covid-19. This review study of 111 studies aimed to identify where urgent research is required to help understand the potential of chronic fatigue therapies in Covid-19. The study first reviewed disrupted cellular energy production in ME/CFS and increased presence of damaging oxidants. Current therapies for improving cellular energy production in CFS/ME were then reviewed and Ritalin, ubiquinone and mitoquinol mesylate were heavily featured. Antioxidant therapies in CFS/ME were reviewed and observations would suggest that trials in patients with long covid are needed. It was concluded that research in cellular energy production in CFS/ME has been increasing, however remains contradictory due to a lack of a definitive diagnosis, differing disease severity and the huge differences between patients who suffer from CFS/ME. Further research is required in ME/CFS and Covid-19. This study could be used by health care professionals to understand the importance of monitoring symptoms of fatigue post Covid-19 infection and the possible use of ME/CFS treatments.
Abstract
A significant number of SARS-CoV-2 (COVID-19) pandemic patients have developed chronic symptoms lasting weeks or months which are very similar to those described for myalgic encephalomyelitis/chronic fatigue syndrome. This study reviews the current literature and understanding of the role that mitochondria, oxidative stress and antioxidants may play in the understanding of the pathophysiology and treatment of chronic fatigue. It describes what is known about the dysfunctional pathways which can develop in mitochondria and their relationship to chronic fatigue. It also reviews what is known about oxidative stress and how this can be related to the pathophysiology of fatigue, as well as examining the potential for specific therapy directed at mitochondria for the treatment of chronic fatigue in the form of antioxidants. This study identifies areas which require urgent, further research in order to fully elucidate the clinical and therapeutic potential of these approaches.
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9.
Long COVID: An overview.
Raveendran, AV, Jayadevan, R, Sashidharan, S
Diabetes & metabolic syndrome. 2021;15(3):869-875
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SARS-CoV-2 infection (COVID-19) is a major pandemic resulting in considerable mortality and morbidity worldwide. For some people who recover from COVID-19, symptoms persist or new ones develop for weeks or months after infection despite testing PCR negative. This is termed long-COVID or post-COVID syndrome and divided into two stages: post-acute-COVID with symptoms extending beyond three weeks, and chronic-COVID with symptoms extending beyond 12 weeks. Factors that increase the risk for long-COVID include being female, age, having more than five symptoms in the acute stage of infection and pre-existing health conditions. A mild disease course is not exclusive to long-COVID. Typically affected by long-COVID are the pulmonary or cardiovascular system, with neuropsychiatric presentations also being reported. Common symptoms are one or more of the following such as fatigue, breathlessness, cough, chest pain, heart racing, headache, joint pain, muscle pain and weakness, insomnia, pins and needles, diarrhoea, rash, hair loss, impaired balance, neurocognitive issues. Due to the novelty of the virus, the underline pathophysiology of long-COVID still requires further investigation. Contributing factors mentioned include: compromised body functions after illness and inactivity, organ damage, persistent inflammation, altered immune response and auto-antibody generation and viral persistence. The impact of medication, treatments, hospitalisation or associated post-traumatic stress is also urged to be accounted for. Diagnosis of long-COVID is made by thorough history taking, clinical examination and the exclusion of other conditions. For the management of long-COVID, the authors in this review suggest the sub-categorisation depending on the body system most affected to optimize treatment options. Furthermore, it is encouraged that medical treatment should also consider the monitoring for worsening of any pre-existing health conditions post-infection. This review yields a informative summary of the definition, symptom presentations, risk factors, diagnosis and medical treatment options relating to long-COVID.
Abstract
BACKGROUND AND AIMS Long COVID is the collective term to denote persistence of symptoms in those who have recovered from SARS-CoV-2 infection. METHODS WE searched the pubmed and scopus databases for original articles and reviews. Based on the search result, in this review article we are analyzing various aspects of Long COVID. RESULTS Fatigue, cough, chest tightness, breathlessness, palpitations, myalgia and difficulty to focus are symptoms reported in long COVID. It could be related to organ damage, post viral syndrome, post-critical care syndrome and others. Clinical evaluation should focus on identifying the pathophysiology, followed by appropriate remedial measures. In people with symptoms suggestive of long COVID but without known history of previous SARS-CoV-2 infection, serology may help confirm the diagnosis. CONCLUSIONS This review will helps the clinicians to manage various aspects of Long COVID.
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Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders.
Chen, Y, Xu, J, Chen, Y
Nutrients. 2021;13(6)
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Imbalances in the gut microbiota occur in various neurological disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), autism spectrum disorder and depression. Imbalances in key neurotransmitters are associated with the same disorders. This review focuses on the regulatory mechanisms of the intestinal microbiome and its metabolites on cognitive functions and the pathogeneses of these neurodegenerative diseases. The gut microbiota produce neurotransmitters such as glutamate, GABA, serotonin and dopamine or their precursors. These neurotransmitters are not able to cross the blood brain barrier but the precursors are, therefore the gut microbiota is indirectly involved in the regulation of the production of these key neurotransmitters and therefore neuronal activity and cognitive functions of the brain. The findings demonstrate an association between a healthy gut microbiome structure and balanced neurotransmitter levels in the host. Microbial therapy holds huge promise for the treatment of brain disorders. The development of drugs for neurological disorders must also consider effects on the physiology of the gut microbiome.
Abstract
Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among the metabolic, peripheral immune, and central nervous systems via the microbiota-gut-brain axis. However, it is not well understood how the gut microbiome and neurons in the brain mutually interact or how these interactions affect normal brain functioning and cognition. We summarize the mechanisms whereby the gut microbiota regulate the production, transportation, and functioning of neurotransmitters. We also discuss how microbiome dysbiosis affects cognitive function, especially in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.