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The effects of time-restricted eating on sleep, cognitive decline, and Alzheimer's disease.
Ezzati, A, Pak, VM
Experimental gerontology. 2023;171:112033
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The ageing population is expected to double, with one in four people being over 65 years in Western countries by 2050. As a consequence, the presentation of age-related disorders like Alzheimer's disease (AD) and mild cognitive impairment (MCI) is likely to increase. MCI, a pre-stage of dementia, is considered reversible. However, there are no known cures for AD so far. Hence interventions such as lifestyle modifications that can delay the onset and progression of the disease are of great interest. Previous research demonstrated that calorie restriction (CR) and time-restricted eating (TRE) have beneficial effects on brain function. The authors of this article sought to summarize the current evidence of such eating patterns, as well as their underlying mechanisms and potential benefits concerning MCI and AD. The review also looked at sleep - as sleep disturbances are a risk factor and are associated with both conditions - and the effects of sleep on cognitive decline and neuroinflammatory markers. TRE presents itself as a promising intervention as it can restore the integrity of the blood-brain barrier and support healthy brain function whilst reducing oxidative stress and inflammation. Furthermore, it can be leveraged for weight and glucose management. Preliminary results also indicate a positive impact on sleep, with adequate sleep benefiting cognitive health. As this is a relatively new field, there is still much more to be understood about the underlying mechanisms, with the optimal time window for fasting needing to be determined. The authors advocate for more research on how TRE and sleep relates to neurodegenerative disease.
Expert Review
Conflicts of interest:
None
Take Home Message:
- To highlight the potential benefits of time-restricted eating (TRE) as a potential preventative approach to delay the onset and progression of neurodegenerative disease such as AD
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:
- The authors highlight Alzheimer's disease (AD) is the most prevalent neurodegenerative disease affecting over 50 million aging people worldwide. While no cure is known for AD, this review proposes lifestyle interventions such as time-restricted eating (TRE) as a potential approach to delay the onset and progression of a neurodegenerative disease and could hint at autophagic mechanisms
- TRE involves strategically limiting the eating window to 8- to 12-h with fasting—drinking only water and calorie-free coffee/tea—for 12 to 16 h within a 24-h cycle.
Objectives
- To investigate the effects of TRE on sleep and cognitive decline in healthy individuals
Results
- Nine RCTs with varied length between one and sixteen weeks were examined
- A 5-week randomised controlled trial (RCT) showed no significant change in sleep quality between early TRE (fasting between 6 a.m.–3 p.m.), mid-day TRE (11 a.m.–8 p. m.) and control (ad lib intake) in 82 healthy subjects without obesity but the sleep quality improvement was greater in early TRE group (PSQI:Δ=−1.08±1.78vs.Δ=−0.22±2.19andΔ=−0.36±1.73, respectively).
- Sleep quality using the myCircadianClock app reported significant improvement in sleep quality (23 %) following a 12-week single arm intervention of 10-h TRE.
- Following a 16-week TRE intervention sleep duration was reported to be improved from a subjective score of 6 at base line to 8 after 36 weeks in eight overweight and obese subjects; however, the study used a subjective self-assessment survey for measuring sleep duration.
- The Pittsburgh Sleep Quality Index (PSQI) was carried out to assess sleep quality and disturbances in six trials but no trial reported significant improvement in sleep quality using the PSQI survey with TRE
Conclusion
- Authors highlight TRE as promising for its potential to reduce the markers of aging and neurodegenerative disease.
Clinical practice applications:
- To inform practitioners of the potential benefits of TRE that involves limiting the eating window to 8- to 12-h with fasting—drinking only water and calorie-free coffee/tea—for 12 to 16 h within a 24-h cycle.
- TRE may improve regulation of circadian rhythm and autophagy through aligning food intake with circadian rhythm, which coordinates metabolism and physiological functions including glucose, insulin sensitivity, lipid levels, energy expenditure, inflammation, sleep and cognitive function.
- TRE activates a metabolic switch which occurs 12–36 h after fasting is initiated and free fatty acids are released into the blood.
- TRE improved sleep quality and sleep duration, where a longer fasting period in TRE approach (≥12 h fasting) was associated with significantly higher sleep duration.
Considerations for future research:
- The potential benefits of TRE in neurodegenerative diseases such as AD should be further investigated clinically.
- The optimal time to initiate fasting needs to be identified in future trials.
- The potential benefits of TRE in neurodegenerative diseases such as AD in the context of sleep should be further investigated.
Abstract
According to the United Nations, by 2050, one in six individuals will be over age 65 globally, and one in four people would be aged 65 and older in western countries. The unprecedented growth of the aging population is associated with increased age-related disorders like Alzheimer's disease (AD) and Mild cognitive impairment (MCI). To date, no cure is known for AD, thus lifestyle interventions including calorie restriction (CR) and time-restricted eating (TRE) are proposed as potential approach to delay the onset and progression of the disease. Sleep disturbances are common in people with MCI and AD. Moreover, accumulating data indicates that pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8 and IL-10 increase in individuals with AD and MCI versus healthy subjects. Thus, the purpose of the present review is to describe the potential effects of TRE on sleep, cognition decline, and neuroinflammatory markers in humans. Preliminary evidence suggests that TRE may produce neuroprotective effects on cognition and reduce neuroinflammatory markers related to AD in humans. To date, no studies investigated the effects of TRE on sleep disturbances and patients with AD. Thereby, the impact of TRE on cognition in individuals with cognitive decline and AD needs to be investigated further in randomized controlled trials (RCTs).
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The effects of berberine supplementation on cardiovascular risk factors in adults: A systematic review and dose-response meta-analysis.
Zamani, M, Zarei, M, Nikbaf-Shandiz, M, Hosseini, S, Shiraseb, F, Asbaghi, O
Frontiers in nutrition. 2022;9:1013055
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Despite advances in medicine, cardiovascular disease (CVD) still remains the primary cause of deaths worldwide. Many of the risk factors of CVD, such as elevated levels of blood fats, high blood pressure, abdominal obesity and poor blood sugar control, can be improved and managed by behaviour, lifestyle and dietary intervention as well as supplements. Berberine (BBR) is a plant-derived compound, available as a supplement, which has gained the attention of researchers due to its ability to modulate cardiovascular risk factors. This dose-response meta-analysis sought to generate a comprehensive overview of the effect of BBR on the risk factors for CVD in adults. The analysis included 49 randomised clinical trials. The results showed BBR significantly reduced blood fats such as total cholesterol, triglycerites and low-density lipoprotein (LDL). It also improved markers of blood sugar control such as fasting blood sugar levels, insulin, HbA1c, HOMA-IR and blood pressure and body weight, whilst enhancing high-density lipoprotein (HDL). The optimal dose of BBR was 1 g/day for triglycerides, total cholesterol, and weight loss. For insulin and HOMA-IR the best effects were seen with 1.8 g/day and for HDL 5 g/day. The most effective timeframe to impact fasting blood sugars seemed to be 40 weeks, and 50 weeks to influence blood pressure and waist circumference. In conclusion, BBR supplementation had beneficial effects on reducing risk factors for CVD, particularly in subgroups with impaired metabolic health. There was no substantial impact on liver enzymes (AST, ALT) or inflammatory markers (CRP, IL-6). Furthermore the supplement was largely ineffective in people with normal body mass index.
Abstract
UNLABELLED Cardiovascular disease (CVD) is a major concern today. Herbal medicine is one helping way to control CVD risks. One conclusive of herbal medicine is Berberine (BBR) and converse about it still exists, to clarify this issue, this meta-analysis was performed. PubMed/Medline, Scopus, and Web of Science were searched for RCTs in adults on the effect of BBR supplementation on CVD risk factors up to July 2022. The pooled results showed BBR significantly reduced triglyceride (WMD = -23.70 mg/dl; 95%CI -30.16, -17.25; P < 0.001), total cholesterol (WMD = -20.64 mg/dl; 95%CI -23.65, -17.63; P < 0.001), low-density lipoprotein WMD = -9.63 mg/dl; 95%CI, -13.87, -5.39; P < 0.001), fasting blood glucose (FBG) (WMD = -7.74 mg/dl; 95%CI -10.79, -4.70; P < 0.001), insulin (WMD = -3.27 mg/dl; 95%CI -4.46,-2.07; P < 0.001), HbA1c (WMD = -0.45%; 95%CI -0.68, -0.23; P < 0.001), HOMA-IR (WMD = -1.04; 95%CI -1.55, -0.52; P < 0.001), systolic blood pressure (WMD = -5.46 mmHg; 95%CI -8.17, -2.76; P < 0.001), weight (WMD = -0.84; 95%CI -1.34,-0.34; P < 0.001), body mass index (WMD = -0.25 kg/m2; 95%CI -0.46, -0.04; P = 0.020), while increased high-density lipoprotein (HDL) (WMD = 1.37 mg/dl; 95%CI 0.41,2.23; P = 0.005). The optimal dose of BBR was 1 g/day for TG, TC, and weight, 1.8 g/day for insulin and HOMA-IR, and 5 g/day for HDL. FBG's most efficient time frame was 40 weeks from the beginning of supplementation, whereas DBP and waist circumference was 50 weeks. In conclusion, the lipid profile, FBG balance, obesity parameters, and SBP were improved with BBR supplementation. SYSTEMATIC REVIEW REGISTRATION CRD42022347004.
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Effect of Vitamin D Supplementation on Inflammatory Biomarkers in School-Aged Children with Attention Deficit Hyperactivity Disorder.
Samadi, M, Gholami, F, Seyedi, M, Jalali, M, Effatpanah, M, Yekaninejad, MS, Abdolahi, M, Chamari, M, Mohammadzadeh Honarvar, N
International journal of clinical practice. 2022;2022:1256408
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Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent psychiatric and developmental disorders among children and adolescents. Besides clinical impairments, these children have challenges with school performance and independent socioeconomic factors. The aim of this study was to assess the possible effects of vitamin D on inflammatory cytokines (tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)) levels in children with ADHD. This study is a randomised, double-blind, placebo-controlled clinical trial which was conducted on 86 children aged 6–12. Patients were randomly assigned to two groups to receive vitamin D3 or a placebo. Results show children with ADHD taking vitamin D supplementation for 3 months demonstrated a significant increase in serum levels of Vitamin D3. However, serum levels of IL-6 and TNF-α were not significantly influenced by vitamin D administration. Authors conclude that their findings failed to find a favourable effect of 3 months of supplementation with vitamin D on inflammatory cytokines. Thus, they highly recommend conducting further studies with different doses of vitamin D and various designs in addition to differences in the characteristics of participants.
Abstract
METHOD This randomized double-blind, placebo-controlled trial was conducted on 75 school-aged children with a diagnosis of ADHD based on DSM-V criteria. Children were randomly allocated to receive either vitamin D3 (2000 IU/day) or a placebo for 3 months. Serum IL-6, TNF-α, and 25(OH) D were assessed before and after the intervention to determine the effects of vitamin D on the highlighted parameters. RESULTS Serum levels of 25(OH) D increased significantly in the vitamin D group (P=0.01). However, no significant differences in serum IL-6 and TNF-α were found between both groups at the baseline and at the end of the intervention. CONCLUSION The findings revealed that vitamin D supplementation for 3 months is not efficacious in reducing inflammatory cytokines in children with ADHD. Further studies are required to confirm these results.
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Efficacy and Safety of Curcumin and Curcuma longa Extract in the Treatment of Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial.
Zeng, L, Yang, T, Yang, K, Yu, G, Li, J, Xiang, W, Chen, H
Frontiers in immunology. 2022;13:891822
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Arthritic disease is a chronic inflammatory condition affecting one or more joints. Over 100 different forms of arthritis have been identified. Despite their different causes (i.e. degenerative, autoimmune), they share common symptoms such as joint pain, swelling, stiffness, and reduced mobility, which can be disabling in many cases. Drug treatment focuses mainly on limiting the progression of the disease, reducing joint inflammation and managing pain. However, these drugs are associated with many side effects. The rhizome of Curcuma longa (CL), also known as turmeric, has longstanding use as an anti-inflammatory in traditional Asian medicines. Research has affirmed its anti-inflammatory and immunosuppressive properties. Evidence from multiple clinical trials suggests that curcumin, one of the active compounds of CL, can reduce the subjective experience of pain in some conditions and can also improve the symptoms and inflammation associated with arthritis. Hence this systematic review sought to evaluate the efficacy and safety of CL-extract in 5 types of arthritis (including Ankylosing Spondylitis, Rheumatoid Arthritis, Osteoarthritis, Juvenile idiopathic arthritis and gout). The review included 29 randomized controlled trials involving 2396 participants, with dosages ranging from 120 mg to 1500 mg for a period of 4-36 weeks. Overall, curcumin and CL extract appeared to improve inflammation and pain levels in arthritic subjects whilst demonstrating safety with no increases in adverse effects. CL and its active constituents appeared to favourably change immune and inflammatory responses, as well as serum uric acid levels in the reviewed forms of arthritis. However, due to the small sample numbers in the trials and some lower quality studies, the authors advocate to interpret the results with caution until more solid evidence is available.
Abstract
Background: Modern pharmacological research found that the chemical components of Curcuma longa L. are mainly curcumin and turmeric volatile oil. Several recent randomized controlled trials (RCT) have shown that curcumin improves symptoms and inflammation in patients with arthritis. Methods: Pubmed, Cochran Library, CNKI, and other databases were searched to collect the randomized controlled trials (RCTs). Then, the risk of bias of RCTs were assessed and data of RCTs were extracted. Finally, RevMan 5.3 was utilized for meta-analysis. Results: Twenty-nine (29) RCTs involving 2396 participants and 5 types of arthritis were included. The arthritis included Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Osteoarthritis (OA), Juvenile idiopathic arthritis (JIA) and gout/hyperuricemia. Curcumin and Curcuma longa Extract were administered in doses ranging from 120 mg to 1500 mg for a duration of 4-36 weeks. In general, Curcumin and Curcuma longa Extract showed safety in all studies and improved the severity of inflammation and pain levels in these arthritis patients. However, more RCTs are needed in the future to elucidate the effect of Curcumin and Curcuma longa Extract supplementation in patients with arthritis, including RA, OA, AS and JIA. Conclusion: Curcumin and Curcuma longa Extract may improve symptoms and inflammation levels in people with arthritis. However, due to the low quality and small quantity of RCTs, the conclusions need to be interpreted carefully.
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The Effects of Dairy Product and Dairy Protein Intake on Inflammation: A Systematic Review of the Literature.
Nieman, KM, Anderson, BD, Cifelli, CJ
Journal of the American College of Nutrition. 2021;40(6):571-582
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Systemic inflammation contributes to the risk and progression of chronic disease, which is in turn influenced by several factors including diet. The aim of this study was to conduct a systematic review to evaluate the effect of dairy products and dairy protein on markers of inflammation in adults that do not have inflammatory-related disorders. The authors analysed 27 previous randomised controlled trial, of which 19 looked at dairy products, and eight looked at dairy protein (casein or whey). In the trials which evaluated dairy products, 10 reported no effect of the intervention, while eight reported a reduction in at least one biomarker of inflammation. All eight trials that investigated dairy protein intake on markers of inflammation reported no effect. The researchers concluded that the available literature suggests that dairy products and dairy proteins have neutral to beneficial effects on biomarkers of inflammation. Additional clinical studies designed using inflammatory biomarkers as the primary outcome are needed to fully understand the effects of dairy intake on inflammation.
Abstract
Systemic inflammation is associated with obesity and chronic disease risk. Intake of dairy foods is associated with reduced risk of type 2 diabetes and cardiovascular disease; however, the impact of dairy foods on inflammation is not well-established. The objective of this study was to conduct a systematic review to evaluate the effect of dairy product (milk, cheese, and yogurt) and dairy protein consumption on low-grade systemic inflammation in adults without severe inflammatory disorders. A literature search was completed in September 2019 using PubMed and CENTRAL as well as inspection of reference lists from relevant review articles. The search resulted in the identification of 27 randomized controlled trials which were included in this analysis. In the 19 trials which evaluated dairy products, 10 reported no effect of the intervention, while 8 reported a reduction in at least one biomarker of inflammation. All 8 trials that investigated dairy protein intake on markers of inflammation reported no effect of the intervention. The available literature suggests that dairy products and dairy proteins have neutral to beneficial effects on biomarkers of inflammation. Additional clinical studies designed using inflammatory biomarkers as the primary outcome are needed to fully elucidate the effects of dairy intake on inflammation.
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Association of Migraine with Its Comorbidities and Food Specific Immunoglobulin G Antibodies and Inflammatory Cytokines: Cross-Sectional Clinical Research.
Zhao, Z, Jin, H, Yin, Y, Hou, Y, Wang, J, Tang, C, Fu, J
Journal of pain research. 2021;14:2359-2368
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Migraine is a chronic, multifactorial headache with multiple comorbid conditions. Previous studies have shown a correlation between food-specific IgG antibodies and chronic inflammation in migraineurs. IgG antibody detection may therefore be a biomarker for migraine since it plays a crucial role in the pathogenesis of the disease. This cross-sectional clinical trial investigated the relationship between IgG antibodies against food antigens and headaches, gastrointestinal symptoms, anxiety, depression, sleep disorders, dermatosis and inflammatory cytokines such as IL-6, TNFα, and IL-10. In this study, migraine patients who had positive food-specific IgG antibodies had severe migraine, anxiety, gastrointestinal symptoms, and elevated levels of proinflammatory cytokines such as IL-6 and TNFα, indicating a causal relationship. However, further studies are required to determine the immune reaction to food antigens and the effect of eliminating IgG positive foods on migraine and its associated comorbidities. Nevertheless, this study can help healthcare professionals understand how food-specific antibodies play a role in diagnosing and treating migraine.
Abstract
PURPOSE The relationship between food allergy caused by food specific IgG antibodies and migraine has received increased attention in recent years. Here, we aimed to evaluate the effects of food specific IgG antibodies on headache, gastrointestinal symptoms, anxiety, depression, sleep disorders, dermatosis, and serum inflammatory cytokines in migraine patients, and to quantitatively assess the effect of IgG levels on the severity of headache and its comorbidities. METHODS Of 89 migraine patients, those who had one or more food specific IgG antibodies ≥50 U/mL were classified into the IgG positive group, which was then further divided into subgroups based on differing numbers of food allergens. All other subjects were classified into the IgG negative group. We compared the frequency and severity of migraine, anxiety, depression, sleep disorders, dermatosis, and inflammatory cytokines between groups. A regression model was performed to further assess the effect of overall positive IgG concentration and the mediation effect of inflammatory cytokines. RESULTS Participants in the positive IgG group (n = 67) were more likely to have longer time elapsed since diagnosis, more frequent and severe migraine, a higher risk of developing anxiety and gastrointestinal symptoms, along with higher IL-6 and TNF-α. Subgroups with more food allergens generally had worse conditions as well. After adjusting for the inflammatory cytokines, the effect of IgG was reduced. CONCLUSION Migraine patients with positive food specific IgG antibodies had worse migraine, anxiety, and gastrointestinal symptoms. Inflammatory cytokines partially mediate the causal pathway between food specific IgG antibodies, migraine, and migraine comorbidities.
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Effects of Fermented Milk Containing Lacticaseibacillus paracasei Strain Shirota on Constipation in Patients with Depression: A Randomized, Double-Blind, Placebo-Controlled Trial.
Zhang, X, Chen, S, Zhang, M, Ren, F, Ren, Y, Li, Y, Liu, N, Zhang, Y, Zhang, Q, Wang, R
Nutrients. 2021;13(7)
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Constipation is a common complaint among people with depression and may negatively affect their quality of life. In association with this, previous studies have shown a correlation between the reduction of Lactobacillus or Bifidobacterium strains in the gut of patients with major depressive disorder. Thus, this two-arm, parallel-design, randomised, double-blinded, placebo-controlled trial examined the effects of supplementing fermented milk with Lacticaseibacillus paracasei Strain Shirota or LcS (previously known as Lactobacillus casei strain Shirota) on constipation in people with depression. Symptoms of constipation, stool problems, and depressive symptoms improved after 9 weeks of consuming fermented milk containing LcS. The abundance of Adlercreutzia, Megasphaera, and Veillonella increased significantly in the intervention group. In contrast, the abundance of bacteria related to mental disorders such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter significantly decreased after the intervention. After 9 weeks of intervention with LcS, a significant reduction in serum proinflammatory cytokines such as IL-1β, IL-6, and TNF-α was observed in patients with depression. The intervention group also showed a decrease in inflammation-causing bacteria, Surrerella, which correlated with a reduction in proinflammatory cytokines. The mechanisms driving the changes in gut microbial composition, depression, and gastrointestinal symptoms after LcS intervention need to be evaluated in more robust studies. Healthcare professionals can use the results of the study to better understand how probiotics can reduce constipation and depression and improve gut microbial composition.
Abstract
Probiotics have been shown to benefit patients with constipation and depression, but whether they specifically alleviate constipation in patients with depression remains unclear. The aim of this study was to investigate the effect of Lacticaseibacillus paracasei strain Shirota (LcS), formerly Lactobacillus casei strain Shirota, on constipation in patients with depression with specific etiology and gut microbiota and on depressive regimens. Eighty-two patients with constipation were recruited. The subjects consumed 100 mL of a LcS beverage (108 CFU/mL) or placebo every day for 9 weeks. After ingesting beverages for this period, we observed no significant differences in the total patient constipation-symptom (PAC-SYM) scores in the LcS group when compared with the placebo group. However, symptoms/scores in item 7 (rectal tearing or bleeding after a bowel movement) and items 8-12 (stool symptom subscale) were more alleviated in the LcS group than in the placebo group. The Beck Depression Index (BDI) and Hamilton Depression Rating Scale (HAMD) scores were all significantly decreased, and the degree of depression was significantly improved in both the placebo and LcS groups (p < 0.05), but there was no significant difference between the groups. The LcS intervention increased the beneficial Adlercreutzia, Megasphaera and Veillonella levels and decreased the bacterial levels related to mental illness, such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter. Additionally, the interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) levels were significantly decreased in both the placebo and LcS groups (p < 0.05). In particular, the IL-6 levels were significantly lower in the LcS group than the placebo group after the ingestion period (p < 0.05). In conclusion, the daily consumption of LcS for 9 weeks appeared to relieve constipation and improve the potentially depressive symptoms in patients with depression and significantly decrease the IL-6 levels. In addition, the LcS supplementation also appeared to regulate the intestinal microbiota related to mental illness.
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Differential Health Effects on Inflammatory, Immunological and Stress Parameters in Professional Soccer Players and Sedentary Individuals after Consuming a Synbiotic. A Triple-Blinded, Randomized, Placebo-Controlled Pilot Study.
Quero, CD, Manonelles, P, Fernández, M, Abellán-Aynés, O, López-Plaza, D, Andreu-Caravaca, L, Hinchado, MD, Gálvez, I, Ortega, E
Nutrients. 2021;13(4)
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Synbiotic, a mixture of prebiotics and probiotics, is known to improve neurotransmitter interactions, immune, inflammatory, and stress responses by modulating the gut microbial composition. It is also believed that physical activity plays an important role in the modulation of immune function and stress response. The purpose of this triple-blinded, randomized, placebo-controlled pilot study was to evaluate the health benefits of symbiotic intervention in fourteen sedentary students and thirteen soccer players, especially in terms of improving immunophysiological and metabolic parameters. The 300mg of symbiotic intervention contained Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, Bifidobacterium longum ES1(109 colony-forming unit), and fructooligosaccharides (200 mg) plus 1.5 mg of zinc, 8.25 µg of selenium, 0.75 µg of vitamin, and maltodextrin. Following a one-month intervention with synbiotic formulation, soccer players showed improvements in anxiety, sleep quality and stress, a slight reduction in proinflammatory cytokine IL-1β, an exercise-induced significant increase in dopamine and a slight elevation of corticotropin-releasing hormone. For confirmation of results of this pilot study and to assess more significant effects of symbiotic intervention in athletes as well as in the general population, longer-term robust studies are required. The findings of this study can help healthcare professionals understand the extensive health benefits of synbiotic intervention and its relationship to physical activity.
Abstract
The main objective of this research was to carry out an experimental study, triple-blind, on the possible immunophysiological effects of a nutritional supplement (synbiotic, Gasteel Plus®, Heel España S.A.U.), containing a mixture of probiotic strains, such as Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, and Bifidobacterium longum ES1, as well as the prebiotic fructooligosaccharides, on both professional athletes and sedentary people. The effects on some inflammatory/immune (IL-1β, IL-10, and immunoglobulin A) and stress (epinephrine, norepinephrine, dopamine, serotonin, corticotropin-releasing hormone (CRH), Adrenocorticotropic hormone (ACTH), and cortisol) biomarkers were evaluated, determined by flow cytometer and ELISA. The effects on metabolic profile and physical activity, as well as on various parameters that could affect physical and mental health, were also evaluated via the use of accelerometry and validated questionnaires. The participants were professional soccer players in the Second Division B of the Spanish League and sedentary students of the same sex and age range. Both study groups were randomly divided into two groups: a control group-administered with placebo, and an experimental group-administered with the synbiotic. Each participant was evaluated at baseline, as well as after the intervention, which lasted one month. Only in the athlete group did the synbiotic intervention clearly improve objective physical activity and sleep quality, as well as perceived general health, stress, and anxiety levels. Furthermore, the synbiotic induced an immunophysiological bioregulatory effect, depending on the basal situation of each experimental group, particularly in the systemic levels of IL-1β (increased significantly only in the sedentary group), CRH (decreased significantly only in the sedentary group), and dopamine (increased significantly only in the athlete group). There were no significant differences between groups in the levels of immunoglobulin A or in the metabolic profile as a result of the intervention. It is concluded that synbiotic nutritional supplements can improve anxiety, stress, and sleep quality, particularly in sportspeople, which appears to be linked to an improved immuno-neuroendocrine response in which IL-1β, CRH, and dopamine are clearly involved.
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Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents.
Khadke, S, Ahmed, N, Ahmed, N, Ratts, R, Raju, S, Gallogly, M, de Lima, M, Sohail, MR
Virology journal. 2020;17(1):154
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Severe manifestations of COVID-19 infection and mortality are associated with a cytokine storm. This is an excessive inflammatory response to the infection leading to an overproduction of pro-inflammatory signalling molecules, which consequently contributes to tissue and organ damage. This literature review summarised current knowledge, as of June 2020, about virus-associated cytokine storm, virus-host interactions and immunological mechanism, to gain a better understanding of the phenomena observed in COVID-19 infections and devise better treatment strategies. The review briefly outlines the epidemiology of COVID-19, predictors of severity of disease, mode of transmission, testing, viral structure, mechanism of invasion of the host cell, replication and immune invasion and the progression of the four stages of the cytokine storm. The second part of the review discusses antiviral therapeutics of interest with a table summarising drugs, mechanism and available data. This article may be of interest to those who like to delve further into the mechanisms and immune components involved in a cytokine storm and gain an oversight of the pathways targeted by allopathic agents that have been put forward as treatment options.
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage. DISCUSSION We reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS). COVID-19 illness encompasses three main phases. In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling. It effectively blunts an early (IFN) response allowing unchecked viral replication. Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak. Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms, persistent fever, and hemodynamic instability. Important cytokines involved in this phase are interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. This is typically followed by a recovery phase with production of antibodies against the virus. We summarize published data regarding virus-host interactions, key immunological mechanisms responsible for virus-associated CRS, and potential opportunities for therapeutic interventions. CONCLUSION Evidence regarding SARS-CoV-2 epidemiology and pathogenesis is rapidly evolving. A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and other therapeutic interventions.
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Plant-based diets, insulin sensitivity and inflammation in elderly men with chronic kidney disease.
González-Ortiz, A, Xu, H, Avesani, CM, Lindholm, B, Cederholm, T, Risérus, U, Ärnlöv, J, Espinosa-Cuevas, A, Carrero, JJ
Journal of nephrology. 2020;33(5):1091-1101
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Consumption of a plant-based diet in individuals with chronic kidney disease (CKD) is associated with lower risk of disease progression and death, however how this occurs is not fully understood. This cross-sectional study of 418 men with CKD aimed to determine whether a plant-based diet is associated with inflammation and the ability to adequately maintain blood-sugar balance. The results showed that individuals who had a higher intake of plant-based foods were associated with lower levels of inflammation and an increased ability to balance blood sugar levels, which was inversed when lower amounts of plant-based foods were consumed. It was concluded that plant-based diets may have a role in lowering the risk of disease progression and death in individuals with CKD. However, an adequately designed study needs to be performed to investigate If this is due to the reduction in inflammation and increased ability to balance blood-sugars observed in the trial. This study could be used by health care professionals to recommend increased consumption of plant-based foods to individuals with CKD to improve disease outcomes.
Abstract
BACKGROUND In persons with CKD, adherence to plant-based diets is associated with lower risk of CKD progression and death, but underlying mechanisms are poorly characterized. We here explore associations between adherence to plant-based diets and measures of insulin sensitivity and inflammation in men with CKD stages 3-5. METHODS Cross-sectional study including 418 men free from diabetes, aged 70-71 years and with cystatin-C estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and not receiving kidney-specific dietetic advice. Information from 7-day food records was used to evaluate the adherence to a plant-based diet index (PBDi), which scores positively the intake of plant-foods and negatively animal-foods. Insulin sensitivity and glucose disposal rate were assessed with the gold-standard hyperinsulinemic euglycemic glucose clamp technique. Inflammation was evaluated by serum concentrations of C-reactive protein (CRP) and interleukin (IL)-6. Associations were explored through linear regression and restricted cubic splines. RESULTS The majority of men had CKD stage 3a. Hypertension and cardiovascular disease were the most common comorbidities. The median PBDi was 38 (range 14-55). Across higher quintiles of PBDi (i.e. higher adherence), participants were less often smokers, consumed less alcohol, had lower BMI and higher eGFR (P for trend <0.05 for all). Across higher PBDi quintiles, patients exhibited higher insulin sensitivity and lower inflammation (P for trend <0.05). After adjustment for eGFR, lifestyle factors, BMI, comorbidities and energy intake, a higher PBDi score remained associated with higher glucose disposal rate and insulin sensitivity as well as with lower levels of IL-6 and CRP. CONCLUSION In elderly men with non-dialysis CKD stages 3-5, adherence to a plant-based diet was associated with higher insulin sensitivity and lower inflammation, supporting a possible role of plant-based diets in the prevention of metabolic complications of CKD.