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Blood levels of circulating methionine components in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis.
Zhao, Y, Dong, X, Chen, B, Zhang, Y, Meng, S, Guo, F, Guo, X, Zhu, J, Wang, H, Cui, H, et al
Frontiers in aging neuroscience. 2022;14:934070
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Alzheimer’s disease (AD) is a chronic neurodegenerative disease that is characterized by progressive memory loss and cognitive deficits. Mild cognitive impairment (MCI) is a prodromal form of AD that is characterised by neurocognitive dysfunction. However, pathological changes associated with AD begin to occur in the brain at least 10 years before the onset of overt symptoms and clinical manifestations, making the discovery of early diagnostic methods and timely interventions important for AD management. The aim of this study was to determine the relationship between circulating methionine (Met) components and AD/MCI. This study is a systematic review and meta-analysis of thirty studies (10 case– control studies, 10 cohort studies, and 10 cross-sectional studies). Results show that: - individuals with AD compared with controls had significantly increased levels of homocysteine. - for people with MCI, there was no significant difference in blood homocysteine levels in the control group. - there were no differences in blood vitamin B12 levels between patients with AD or MCI and controls. Authors conclude that circulating Met components affect patients with AD compared to cognitively normal individuals, with patients exhibiting higher blood homocysteine levels. Additionally, high Met and S-adenosylmethionine levels are risk factors for AD, which supports the association between Met cycle components and AD/MCI.
Abstract
BACKGROUND Circulating methionine components have been reported to be associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI), although outcomes are not always consistent. MATERIALS AND METHODS Database searching was conducted using PubMed, Embase, Cochrane Library, and Web of Science from inception to 26 December 2021. In this study, two reviewers independently identified eligible articles and extracted the data. We used Joanna Briggs Institute (JBI) Critical Appraisal tools to assess the overall quality of the included studies. STATA software was employed to perform meta-analysis evaluating the standardized mean difference (SMD) with its 95% confidence intervals (CIs) using random-effects models. Evidence quality was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RESULTS Totally, 30 observational studies were eligible for inclusion. Compared with cognitively normal controls, patients with AD had increased homocysteine (Hcy) levels in the blood [standardized mean difference (SMD) = 0.59, 95% confidence interval [CI]: 0.36-0.82, P = 0.000], plasma (SMD = 0.39, 95% CI: 0.23-0.55, P = 0.000), and serum (SMD = 1.56, 95% CI: 0.59-2.95, P = 0.002). Patients with MCI were not significantly different from controls (SMD = 0.26, 95% CI: -0.07-0.58, P = 0.127). Patients with AD or MCI did not significantly differ from controls of blood vitamin B12 levels, AD (SMD = -0.05, 95% CI: -0.19-0.08, P = 0.440), or MCI (SMD = 0.01, 95% CI: -0.16-0.17, P = 0.94). Some cohort studies have suggested that higher Hcy, methionine, and S-adenosylmethionine levels may accelerate cognitive decline in patients with MCI or AD, and vitamin B12 deficiency is a risk factor for the disease; however, the results of other studies were inconsistent. According to the GRADE system, all these outcomes scored very low to low quality, and no high-quality evidence was found. CONCLUSION Only Hcy levels in the plasma and serum were found to be inversely related to the risk of AD. However, due to the low quality of supporting these results, high-quality studies are needed to verify these findings. SYSTEMATIC REVIEW REGISTRATION http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022308961.
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Zinc supplementation affects favorably the frequency of migraine attacks: a double-blind randomized placebo-controlled clinical trial.
Ahmadi, H, Mazloumi-Kiapey, SS, Sadeghi, O, Nasiri, M, Khorvash, F, Mottaghi, T, Askari, G
Nutrition journal. 2020;19(1):101
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Migraine is a chronic neurovascular disorder. Patients with this disorder suffer from severe headaches and also nausea, vomiting, photophobia, and phonophobia during a migraine attack. Several supplementary treatments have been suggested for the management of migraine symptoms. Among these methods, there is the supplementation with micronutrients. The aim of this study was to examine the effect of zinc supplementation on characteristics of migraine attacks in migraine patients. This study is a double-blind randomized clinical trial which included migraine patients, with an age range between 20 and 60 years. Patients were stratified based on age (20–40 and 40–60 years), gender (male and female), and body mass index (18.5–24.9 and 25–30) into different blocks. Then, they were randomly allocated to the intervention or control groups. Results show that when compared to the placebo group, zinc supplementation resulted in a significant reduction in headache severity and migraine attacks frequency. However, the effect on headache severity became statistically non-significant when baseline values of headache severity and potential confounders were taken into account. Authors conclude that zinc supplementation was beneficial for migraine attack frequency but not for migraine attack duration and headache daily results.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Inadequate zinc intake may drive migraine frequency.
- Zinc supplementation may enhance the effectiveness of routine migraine treatment in reducing migraine frequency.
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:
Migraines, characterised by severe headaches, nausea, vomiting, photophobia, and phonophobia affect approximately 10-20% of the global population. The authors refer to observational studies that have identified a moderate rate of zinc deficiency amongst migraine sufferers.
Zinc, an essential trace mineral, may prove beneficial as a supplement to reduce migraine symptoms and frequency possibly due to its effects on the nervous system and its antioxidant and anti-inflammatory capacity..
This double blind randomised clinical trial analysed the effects of 220mg of zinc sulphate (50mg of elemental zinc) combined with a routine migraine treatment versus a control group receiving a placebo and the routine treatment on symptoms of migraine attacks. The study duration was 8 weeks occurring from January 2016 to April 2016. Each group consisted of 40 participants between the ages of 20 and 60 with >5 years of migraines or migraine symptoms.
When compared to the placebo group, zinc supplementation demonstrated:
- A reduction in headache severity (− 1.75 ± 1.79 vs. -0.80 ± 1.57; P = 0.01). This result became statistically non-significant when the analysis was adjusted for potential confounders and baseline values of headache severity.
- A reduction in migraine attacks frequency (− 2.55 ± 4.32 vs. -0.42 ± 4.24; P = 0.02).
Clinical practice applications:
This randomised controlled trial highlights that zinc supplementation combined with routine migraine treatment (200/500 mg sodium valproate (such as Depakin), 50/100 mg sumatriptan, or 1 mg ergotamine) may assist in the reduction of migraine attack frequency amongst migraine sufferers within 8 weeks.
Compliance rate for this study was very high at 100% and there were no adverse effects reported suggesting a potentially safe and convenient treatment for migraine sufferers.
Considerations for future research:
- Further trials with better dietary controls would be useful to eliminate potential confounders.
- Use of CONSORT guidelines for reporting randomised trials would strengthen research reporting.
- Analysis of biomarkers may assist in identifying the mechanisms in which zinc may relieve migraine symptoms..
- Larger randomised controlled trials with increased sample sizes and longer durations are needed in order to definitively determine the effect of zinc supplementation on migraine attacks and any differences between genders.
- Additional studies trialling various zinc dosages and forms may provide insight into an optimal zinc dose and form for migraine attacks.
Abstract
BACKGROUND Observational studies have shown a link between zinc deficiency and migraine headaches. We aimed to examine the effect of zinc supplementation on the characteristics of migraine attacks in patients with migraine. METHODS This randomized clinical trial was conducted on 80 patients with migraine. Patients were randomly assigned to receive either zinc sulfate (220 mg/d zinc sulfate) or placebo (lactose) for 8 weeks. Anthropometric measures, serum zinc concentrations, and characteristics of migraine attacks (headache severity, frequency and duration of migraine attacks, and headache daily results) were assessed at baseline and end of the trial. RESULTS Compared with the placebo, zinc supplementation resulted in a significant reduction in headache severity (- 1.75 ± 1.79 vs. -0.80 ± 1.57; P = 0.01) and migraine attacks frequency (- 2.55 ± 4.32 vs. -0.42 ± 4.24; P = 0.02) in migraine patients. However, the observed reduction for headache severity became statistically non-significant when the analysis was adjusted for potential confounders and baseline values of headache severity. Other characteristics of migraine attacks including the duration of attacks and headache daily results were not altered following zinc supplementation either before or after controlling for covariates. CONCLUSION Zinc supplementation had a beneficial effect on the frequency of migraine attacks in migraine patients. Additional well-designed clinical trials with a long period of intervention and different dosages of zinc are required. TRIAL REGISTRATION CODE IRCT20121216011763N23 at www.irct.ir .
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PROFAST: A Randomized Trial Assessing the Effects of Intermittent Fasting and Lacticaseibacillus rhamnosus Probiotic among People with Prediabetes.
Tay, A, Pringle, H, Penning, E, Plank, LD, Murphy, R
Nutrients. 2020;12(11)
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The prevalence of diabetes is increasing worldwide, and with it, the risk of cardiovascular disease is also increasing. Intermittent fasting has been shown to reduce weight and improve glycaemic control. Weight control and glycaemic control were also improved with probiotic Lacticaseibacillus rhamnosus HN001 supplementation. This pilot, 12-week, double-blinded, two-armed, randomized 1:1 study aimed to investigate the combined effects of intermittent fasting with daily probiotic Lacticaseibacillus rhamnosus HN001 supplementation on glycaemic management in participants with prediabetes. For two days, participants restricted their calorie intake to 600-650 kcal, followed by five days of ad libitum consumption (5:2). Intermittent fasting for 12 weeks improved glycaemic control (reduced HbA1c) and reduced body weight by 5%. The supplementation with Lacticaseibacillus rhamnosus HN001 did not significantly improve these outcomes. Probiotic supplementation significantly improved mental health and social functioning in participants. There is a need for further large, robust studies to assess the effects of intermittent fasting alone and when it is combined with different exercise forms and different prebiotic and probiotic supplements on cardiometabolic markers and mental health. The findings of this study may be useful to healthcare professionals in understanding the effects of fasting on metabolism as well as the psychological benefits of Lacticaseibacillus rhamnosus HN001 supplementation.
Abstract
Both intermittent fasting and specific probiotics have shown promise in improving glucose tolerance with a potential for synergistic effects through alterations to gut microbiota. In this randomized, double-blinded, two-arm feasibility study, we investigated whether intermittent fasting, supplemented with Lacticaseibacillus rhamnosus HN001 probiotic, reduces HbA1c in individuals with prediabetes. All participants with HbA1c 40-50 mmol/mol commenced intermittent fasting (2 days per week of calorie restriction to 600-650 kcal/day) and were randomized 1:1 to either daily probiotic (Lacticaseibacillus rhamnosus HN001) or placebo for 12 weeks. The primary outcome was a change in HbA1c. Secondary outcomes included changes in anthropometry, body composition, glucoregulatory markers, lipids, hunger hormones, liver enzymes, inflammatory markers, gut hormones, calorie and macronutrient intake, quality of life, hunger, mood and eating behavior. Of 33 participants who commenced the trial, 26 participants (mean age 52 years, body mass index (BMI) 34.7 kg/m2) completed the intervention (n = 11 placebo, n = 15 probiotic). HbA1c decreased from 43 ± 2.7 mmol/mol to 41 ± 2.3 mmol/mol, p < 0.001, with average of 5% weight loss. No significant between-group differences were seen in primary or secondary outcomes except for social functioning (p = 0.050) and mental health (p = 0.007) scores as improvements were seen in the probiotic group, but not in the placebo group. This study shows additional psychological benefits of probiotic supplementation during intermittent fasting to achieve weight loss and glycemic improvement in prediabetes.
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Bacterial Metabolites of Human Gut Microbiota Correlating with Depression.
Averina, OV, Zorkina, YA, Yunes, RA, Kovtun, AS, Ushakova, VM, Morozova, AY, Kostyuk, GP, Danilenko, VN, Chekhonin, VP
International journal of molecular sciences. 2020;21(23)
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Depression is multifactorial disease and it is the most common type of psychiatric disorder. Literature indicates that there are significant differences between the gut microbiota (GM) of patients with depression and healthy controls. The aim of this review was to examine (a) various low-molecular compounds as potential biomarkers of depression in correlation with the metabolism of the GM, and (b) ways to correct the microbiota imbalance. Results show that: - the use of the GM biomarkers, reflecting the neuromodulatory [the process by which nervous activity is regulated through classes of neurotransmitters], immunomodulatory [the process by which the body’s immune system is altered] and antioxidant statuses of the host organism, in the analysis of metagenomic [the study of a collection of genetic material (genomes) from a mixed community of organisms] data from patients with neuropsychiatric diseases, is gaining currency. - diet remains one of the most effective measures that can be taken to restore the microbial balance in the gut and alleviate the symptoms of depression. - a healthy diet during the depression therapy, along with the application of probiotics and psychobiotics, may potentially improve the course of the disease and contribute to the progress of treatment. Authors conclude that further progress in the practical understanding of the role of the GM in depression will greatly depend on correct planning of future metagenomic studies.
Abstract
Depression is a global threat to mental health that affects around 264 million people worldwide. Despite the considerable evolution in our understanding of the pathophysiology of depression, no reliable biomarkers that have contributed to objective diagnoses and clinical therapy currently exist. The discovery of the microbiota-gut-brain axis induced scientists to study the role of gut microbiota (GM) in the pathogenesis of depression. Over the last decade, many of studies were conducted in this field. The productions of metabolites and compounds with neuroactive and immunomodulatory properties among mechanisms such as the mediating effects of the GM on the brain, have been identified. This comprehensive review was focused on low molecular weight compounds implicated in depression as potential products of the GM. The other possible mechanisms of GM involvement in depression were presented, as well as changes in the composition of the microbiota of patients with depression. In conclusion, the therapeutic potential of functional foods and psychobiotics in relieving depression were considered. The described biomarkers associated with GM could potentially enhance the diagnostic criteria for depressive disorders in clinical practice and represent a potential future diagnostic tool based on metagenomic technologies for assessing the development of depressive disorders.
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Pharmaceutical Interventions in Chronic Fatigue Syndrome: A Literature-based Commentary.
Richman, S, Morris, MC, Broderick, G, Craddock, TJA, Klimas, NG, Fletcher, MA
Clinical therapeutics. 2019;41(5):798-805
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Myalgic encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/ CFS), is a disease characterized by an inability to exert oneself physically, often coupled with a combination of other symptoms, including sleep disorders, severe unpredictable pain, and compromised cognitive abilities. The aim of this review was to delineate a number of the more prominent treatments for ME/CFS into different categories and evaluate the methods and results of corresponding drug trials. Results indicate that: • antiviral drugs appear to show limited efficacy in treating ME/CFS over a broad demographic. • there is a lack of clinical research focusing on the use of specific cyclooxygenase-2 inhibitors [analgesic] to treat ME/CFS. • antidepressants may be of use in delivering improvements in the quality of life of patients with ME/CFS. • recalibration of endocrine-immune regulation may be involved in supporting the persistence of ME/CFS and may be responsible at least in part for its resistance to single agent interventions. Authors conclude that there is a great need for larger, longitudinal studies focused on a more clearly defined subset of ME/CFS as well as a greater consideration of potential synergies between interventions and the suitability of combination therapies.
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by prolonged periods of fatigue, chronic pain, depression, and a complex constellation of other symptoms. Currently, ME/CFS has no known cause, nor are the mechanisms of illness well understood. Therefore, with few exceptions, attempts to treat ME/CFS have been directed mainly toward symptom management. These treatments include antivirals, pain relievers, antidepressants, and oncologic agents as well as other single-intervention treatments. Results of these trials have been largely inconclusive and, in some cases, contradictory. Contributing factors include a lack of well-designed and -executed studies and the highly heterogeneous nature of ME/CFS, which has made a single etiology difficult to define. Because the majority of single-intervention treatments have shown little efficacy, it may instead be beneficial to explore broader-acting combination therapies in which a more focused precision-medicine approach is supported by a systems-level analysis of endocrine and immune co-regulation.
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Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches.
Mitchell, N, Hewitt, CE, Jayakody, S, Islam, M, Adamson, J, Watt, I, Torgerson, DJ
Nutrition journal. 2011;10:85
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The exact causes of migraine are unknown, but it is thought that it may be a culmination of several different factors, such as stress, altered sleep patterns, weather and hypersensitivity to foods. Testing for food intolerances is a challenging process and several methods can be employed to test. This study aimed to determine the effectiveness of using a type of testing known as the enzyme linked immune-sorbent assay (ELISA), which tests the body’s delayed immune reaction to foods, and whether eliminating foods based on results from this test would help migraine sufferers. The results showed that 4 weeks of eliminating foods based on the ELISA test decreased migraines, however this was not sustained to 12 weeks of food elimination. It was concluded that in the short-term, eliminating foods based on results from the ELISA decreased headache frequency, but this could not be sustained long-term. This study could be used by healthcare professionals to understand that diet elimination based on measuring the body’s delayed immune response may have limited effects on migraines.
Abstract
BACKGROUND Research suggests that food intolerance may be a precipitating factor for migraine like headaches. AIM: To evaluate the effectiveness of the ELISA (Enzyme Linked Immuno-Sorbent Assay) Test and subsequent dietary elimination advice for the prevention of migraine like headaches. DESIGN Randomised controlled trial. SETTING Community based volunteers in the UK. PARTICIPANTS Volunteers who met the inclusion criteria for migraine like headaches and had one or more food intolerance were included in the study. Participants received either a true diet (n = 84) or a sham diet (n = 83) sheet. Participants were advised to remove the intolerant foods from their diet for 12 weeks. MAIN OUTCOME MEASURES Number of headache days over a 12 week period (item A MIDAS questionnaire). Other measures includes the total MIDAS score and total HIT-6 score. RESULTS The results indicated a small decrease in the number of migraine like headaches over 12 weeks, although this difference was not statistically significant (IRR 1.15 95% CI 0.94 to 1.41, p = 0.18). At the 4 week assessment, use of the ELISA test with subsequent diet elimination advice significantly reduced the number of migraine like headaches (IRR 1.23 95%CI 1.01 to 1.50, p = 0.04). The disability and impact on daily life of migraines were not significantly different between the true and sham diet groups. CONCLUSIONS Use of the ELISA test with subsequent diet elimination advice did not reduce the disability or impact on daily life of migraine like headaches or the number of migraine like headaches at 12 weeks but it did significantly reduce the number of migraine like headaches at 4 weeks.