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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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Transform-Us! cluster RCT: 18-month and 30-month effects on children's physical activity, sedentary time and cardiometabolic risk markers.
Salmon, J, Arundell, L, Cerin, E, Ridgers, ND, Hesketh, KD, Daly, RM, Dunstan, D, Brown, H, Della Gatta, J, Della Gatta, P, et al
British journal of sports medicine. 2023;57(5):311-319
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Regular physical activity is beneficial to children’s physical, social and mental health. However, most children fail to meet the recommended 60+ min of moderate-intensity to vigorous-intensity physical activity every day. The Transform-Us! school-based and home-based intervention was developed to determine the impact of strategies to promote children’s moderate-to-vigorous physical activity versus reduce sedentary behaviour or a combination of these strategies, on behavioural and health outcomes. The main aim of this study was to determine the efficacy of the independent and combined intervention approaches to promoting physical activity and reducing sedentary behaviour on children’s moderate-to-vigorous physical activity and sedentary time after 18 and 30 months compared with usual practice. This study is a 30-month 2×2 factorial design cluster randomised controlled trial delivered in 20 primary schools with additional home intervention components. After recruitment, schools were then randomly allocated to one of four groups. Results show that Transform-Us! had stronger effects on children’s sedentary behaviour than physical activity in both the physical activity (PA) and sedentary behaviour (SB) interventions, and there were beneficial effects on children’s adiposity for both intervention approaches. However, no clear conclusions could be drawn regarding which intervention (PA or SB) had the strongest or more consistent effects on children’s health outcomes. Authors conclude that, based on their findings, government education departments and schools should consider adopting and implementing whole-of-school programmes to promote children’s physical activity and reduce sitting through active pedagogy and supportive social and physical environments at school and home to benefit children’s sedentary time and some markers of cardiometabolic health.
Abstract
OBJECTIVE To test the efficacy of the Transform-Us! school- and home-based intervention on children's physical activity (PA), sedentary behaviour (SB) and cardiometabolic risk factor profiles. METHODS A 30-month 2×2 factorial design cluster randomised controlled trial delivered in 20 primary schools (148 Year 3 classes) in Melbourne, Australia (2010-2012), that used pedagogical and environmental strategies to reduce and break up SB, promote PA or a combined approach, compared with usual practice. Primary outcomes (accelerometry data; n=348) were assessed at baseline, 18 and 30 months. Secondary outcomes included body mass index (BMI) and waist circumference (WC) (n=564), blood pressure (BP) (n=537) and biomarkers (minimum n=206). Generalised linear mixed models estimated the interactive effects of the PA and SB interventions on the outcomes. If there was no interaction, the main effects were assessed. RESULTS At 18 months, there were intervention effects on children's weekday SB (-27 min, 95% CI: -47.3 to -5.3) for the PA intervention, and on children's average day PA (5.5 min, 95% CI: 0.1 to 10.8) for the SB intervention. At 30 months, there was an intervention effect for children's average day SB (-33.3 min, 95% CI: -50.6 and -16.0) for the SB intervention. Children's BMI (PA and SB groups) and systolic BP (combined group) were lower, and diastolic BP (PA group) was higher. There were positive effects on WC at both time points (SB intervention) and mixed effects on blood parameters. CONCLUSIONS The Transform-Us! PA and SB interventions show promise as a pragmatic approach for reducing children's SB and adiposity indicators; but achieving substantial increases in PA remains challenging. TRIAL REGISTRATION ISRCTN83725066; ACTRN12609000715279.
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Effects of whey and soy protein supplementation on inflammatory cytokines in older adults: a systematic review and meta-analysis.
Prokopidis, K, Mazidi, M, Sankaranarayanan, R, Tajik, B, McArdle, A, Isanejad, M
The British journal of nutrition. 2023;129(5):759-770
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Reduced muscle mass and reduction in physical activity may lead to sarcopenia in older people. Age-related sarcopenia is associated with increased systemic low-grade inflammation and obesity. Protein supplementation is found to be beneficial in reducing circulating pro-inflammatory cytokines in old people. Previous research has shown that supplementation with isolated whey and soy protein reduces the levels of inflammatory cytokines in older adults. However, there is limited research on intact whey and soy protein supplementation in reducing age-related inflammation. This systematic review and meta-analysis investigated the effect of intact whey and soy protein on serum inflammatory markers such as C-reactive protein (CRP), Interleukin-6 (IL6) and TNF-α in older adults. The results of this meta-analysis show a significant reduction in circulating IL-6 and TNF-α levels after the supplementation with whey and soy protein. The addition of soy isoflavones resulted in a further decline in serum CRP levels. Subgroup analysis showed that the whey protein supplementation significantly improved sarcopenia and pre-frailty. Healthcare professionals can use the result of this systematic review and meta-analysis to understand the anti-inflammatory properties of intact whey and soy protein and soy isoflavones. However, further robust studies are required to assess the anti-inflammatory properties of whey and soy protein due to the high heterogeneity of included studies in this review.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Nutritional strategies such as whey and soy protein supplementation may be regarded as safe and effective to attenuate adverse changes in muscle mass with ageing, however need to be considered alongside individual dietary intake and health status.
- Consider optimising protein intake and quality of protein through diet as an alternative or first line strategy.
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
- A decline in muscle mass and physical capacity, known as sarcopenia, may start in the fourth decade with accumulation of adiposity, resulting in elevated circulating proinflammatory cytokines.
- Systematic and local elevation of oxidative stress and reactive oxygen species accumulation may accelerate age-related muscle wasting, however may be mitigated with antioxidant nutrients.
- This SR and MA evaluated whey and soy proteins effects on interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) in older adults.
Methods
SR followed PRISMA guidelines, was registered on PROSPERO and included 31 RCT studies published in English between 2004-21. Intervention group received soy/whey supplements and comparator group received a placebo; circulating levels of CRP, IL-6 and/or TNF-α were assessed. MA used random-effects to calculate the pooled effects. Overall quality of evidence was rated as moderate.
Results
Males and females with a mean age 50 - 80 years were included.
Whey protein:
- IL-6 levels were reduced significantly (Number of studies (k) = 12, Mean Difference (MD): −0·79, 95 % Confidence Interval (CI): −1·15, −0·42, p< 0.01), however, high heterogeneity was observed (I2 = 96 %).
- Treatment duration ≤ 8 weeks showed a significant reduction in serum CRP (k = 4, MD: –0·30, 95 % CI: –0·39, –0·21, I2 = 0 %) compared with > 8 weeks (k = 6, MD: 0·13, 95 % CI: –0·13, 0·40, I2 = 9 %), whereas TNF-α and IL-6 remained unaltered.
- Individuals with sarcopenia and pre-frailty displayed a significant reduction of IL-6 (k = 3, MD: –0·98, 95 % CI: –1·56, –0·39, I2 = 0 %) but no benefits were observed for CRP or TNF.
Soy protein:
- There was a significant reduction in TNF-α (k = 6, MD: −0·16, 95 % CI: −0·26, p<0·05).
- The addition of isoflavones demonstrated a significant decrease in TNF-α (k = 5, MD: –0·20, 95 % CI: –0·31, –0·08, I2 = 34 %) but an increase in CRP (k = 7, MD: 0·53, 95 % CI: 0·12, 0·94), however high heterogeneity was observed in the latter (I2 = 91 %).
Conclusion
- The study found a significant reduction in IL-6 following whey protein with effects augmented in those with frailty and sarcopenia and a significant reduction in TNF-α following soy protein with effects augmented by additional soy isoflavones, possibly due to antioxidant effects.
Clinical practice applications:
- Consider whey and/or soy protein supplementation in older adults particularly those reported with pre-frailty and sarcopenia as an effective and safe strategy to attenuate low-grade inflammation and associated risks.
- Soy isoflavones may have additional antioxidant benefits for older adults although further research is needed to confirm this due to high heterogeneity found.
Considerations for future research:
Future research could:
- Evaluate other factors which influence the inflammatory profile such as nutrient density, vitamins and minerals supplementation and exercise.
- Include those with co-morbidities and healthy populations with placebo comparator groups.
- Evaluate dose and type of soy isoflavones on circulating inflammatory markers and the effect of combined whey and soy protein.
Abstract
BACKGROUND AND AIMS Low-grade inflammation is a mediator of muscle proteostasis. This study aimed to investigate the effects of isolated whey and soy proteins on inflammatory markers. METHODS We conducted a systematic literature search of randomised controlled trials (RCT) through MEDLINE, Web of Science, Scopus and Cochrane Library databases from inception until September 2021. To determine the effectiveness of isolated proteins on circulating levels of C-reactive protein (CRP), IL-6 and TNF-α, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42021252603). RESULTS Thirty-one RCT met the inclusion criteria and were included in the systematic review and meta-analysis. A significant reduction of circulating IL-6 levels following whey protein [Mean Difference (MD): -0·79, 95 % CI: -1·15, -0·42, I2 = 96 %] and TNF-α levels following soy protein supplementation (MD: -0·16, 95 % CI: -0·26, -0·05, I2 = 68 %) was observed. The addition of soy isoflavones exerted a further decline in circulating TNF-α levels (MD: -0·20, 95 % CI: -0·31, -0·08, I2 = 34 %). According to subgroup analysis, whey protein led to a statistically significant decrease in circulating IL-6 levels in individuals with sarcopenia and pre-frailty (MD: -0·98, 95 % CI: -1·56, -0·39, I2 = 0 %). These findings may be dependent on participant characteristics and treatment duration. CONCLUSIONS These data support that whey and soy protein supplementation elicit anti-inflammatory effects by reducing circulating IL-6 and TNF-α levels, respectively. This effect may be enhanced by soy isoflavones and may be more prominent in individuals with sarcopenia.
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Elucidation of Prebiotics, Probiotics, Postbiotics, and Target from Gut Microbiota to Alleviate Obesity via Network Pharmacology Study.
Oh, KK, Gupta, H, Min, BH, Ganesan, R, Sharma, SP, Won, SM, Jeong, JJ, Lee, SB, Cha, MG, Kwon, GH, et al
Cells. 2022;11(18)
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The prevalence of obesity and associated comorbidities, such as diabetes, heart attack, hypertension, and cancer, is increasing worldwide. Microbes in the gut may play a significant role in the management of obesity by fermenting dietary fibres and producing metabolites such as short-chain fatty acids and flavonoids. In this meta-analysis, data were retrieved about gut microbial metabolites from the gutMGene database to evaluate the beneficial effects of prebiotics, probiotics, and postbiotics on key targets of obesity. Tryptophan was converted into beneficial metabolites such as indole by Escherichia coli, and isoflavones were converted into equol by Lactobacillus paracasei JS1. A positive effect may be exerted by these metabolites on the treatment of obesity. According to this meta-analysis, equol can reduce the levels of Interleukin-6, one of the inflammatory cytokines associated with obesity. Prebiotic isoflavone is fermented by probiotic Lactobacillus paracasei JS1 to produce equol, a postbiotic that inhibits the action of interleukin-6 and exerts a beneficial effect on obesity. In addition to understanding the relationship between prebiotics, probiotics, and postbiotics, healthcare professionals can use the results of this study to modulate the pathophysiology of obesity. It is necessary to conduct further rigorous research in order to evaluate the pharmacological value of the elements.
Abstract
The metabolites produced by the gut microbiota have been reported as crucial agents against obesity; however, their key targets have not been revealed completely in complex microbiome systems. Hence, the aim of this study was to decipher promising prebiotics, probiotics, postbiotics, and more importantly, key target(s) via a network pharmacology approach. First, we retrieved the metabolites related to gut microbes from the gutMGene database. Then, we performed a meta-analysis to identify metabolite-related targets via the similarity ensemble approach (SEA) and SwissTargetPrediction (STP), and obesity-related targets were identified by DisGeNET and OMIM databases. After selecting the overlapping targets, we adopted topological analysis to identify core targets against obesity. Furthermore, we employed the integrated networks to microbiota-substrate-metabolite-target (MSMT) via R Package. Finally, we performed a molecular docking test (MDT) to verify the binding affinity between metabolite(s) and target(s) with the Autodock 1.5.6 tool. Based on holistic viewpoints, we performed a filtering step to discover the core targets through topological analysis. Then, we implemented protein-protein interaction (PPI) networks with 342 overlapping target, another subnetwork was constructed with the top 30% degree centrality (DC), and the final core networks were obtained after screening the top 30% betweenness centrality (BC). The final core targets were IL6, AKT1, and ALB. We showed that the three core targets interacted with three other components via the MSMT network in alleviating obesity, i.e., four microbiota, two substrates, and six metabolites. The MDT confirmed that equol (postbiotics) converted from isoflavone (prebiotics) via Lactobacillus paracasei JS1 (probiotics) can bind the most stably on IL6 (target) compared with the other four metabolites (3-indolepropionic acid, trimethylamine oxide, butyrate, and acetate). In this study, we demonstrated that the promising substate (prebiotics), microbe (probiotics), metabolite (postbiotics), and target are suitable for obsesity treatment, providing a microbiome basis for further research.
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Effect of Lactoferrin Supplementation on Inflammation, Immune Function, and Prevention of Respiratory Tract Infections in Humans: A Systematic Review and Meta-analysis.
Berthon, BS, Williams, LM, Williams, EJ, Wood, LG
Advances in nutrition (Bethesda, Md.). 2022;13(5):1799-1819
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Human and bovine milk contains Lactoferrin, an iron-binding glycoprotein that may modulate immune function and has antimicrobial and antioxidant properties. In this systematic review and meta-analysis, 25 heterogeneous studies were included to evaluate the efficacy of lactoferrin supplementation on systemic inflammation, immune function, and respiratory tract infections in children and adults with various inflammatory conditions. Supplementation with Lactoferrin reduced only a few inflammatory markers, and beneficial effects were observed in less than half of the studies included. However, a beneficial effect was observed when the intervention was continued for at least three months, and dosages, such as 35 mg/d to 833 mg/d in infants, and 400 mg/d to 600 mg/d in adults, were also found to be beneficial. By modulating the immune system, lactoferrin supplementation reduces respiratory tract infections in children and infants. Based on the findings of this study, healthcare professionals may be able to understand the beneficial effects of Lactoferrin supplementation on immune modulation, inflammation reduction, and respiratory tract infections when supplemented as a combination with other supplements or as Lactoferrin alone. However, it is necessary to conduct further robust research to confirm the clinical effectiveness of Lactoferrin supplementation since the current research is limited in number and heterogeneous in nature.
Abstract
Lactoferrin (Lf) is a glycoprotein present in human and bovine milk with antimicrobial and immune-modulating properties. This review aimed to examine the evidence for the effect of Lf supplementation on inflammation, immune function, and respiratory tract infections (RTIs) in humans. Online databases were searched up to December 2020 to identify relevant, English-language articles that examined the effect of Lf supplementation in human subjects of all ages, on either inflammation, immune cell populations or activity, or the incidence, duration, or severity of respiratory illness or RTIs. Twenty-five studies (n = 20 studies in adults) were included, of which 8 of 13 studies (61%) in adults reported a decrease in at least 1 systemic inflammatory biomarker. Immune function improved in 6 of 8 studies (75%) in adults, with changes in immune cell populations in 2 of 6 studies (33%), and changes in immune cell activity in 2 of 5 studies (40%). RTI outcomes were reduced in 6 of 10 studies (60%) (n = 5 in adults, n = 5 in children), with decreased incidence in 3 of 9 studies (33%), and either decreased frequency (2/4, 50%) or duration (3/6, 50%) in 50% of studies. In adults, Lf reduced IL-6 [mean difference (MD): -24.9 pg/mL; 95% CI: -41.64, -8.08 pg/mL], but not C-reactive protein (CRP) [standardized mean difference: -0.09; 95% CI: -0.82, 0.65], or NK cell cytotoxicity [MD: 4.84%; 95% CI: -3.93, 13.60%]. RTI incidence was reduced in infants and children (OR: 0.78; 95% CI: 0.61, 0.98) but not in adults (OR: 1.00; 95% CI: 0.76, 1.32). Clinical studies on Lf supplementation are limited, although findings show 200 mg Lf/d reduces systemic inflammation, while formulas containing 35-833 mg Lf/d may reduce RTI incidence in infants and children, suggesting improved immune function. Future research is required to determine optimal supplementation strategies and populations most likely to benefit from Lf supplementation. This trial was registered at PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021232186) as CRD42021232186.
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An oleuropein-based dietary supplement may improve joint functional capacity in older people with high knee joint pain: findings from a multicentre-RCT and post hoc analysis.
Horcajada, MN, Beaumont, M, Sauvageot, N, Poquet, L, Saboundjian, M, Costes, B, Verdonk, P, Brands, G, Brasseur, J, Urbin-Choffray, D, et al
Therapeutic advances in musculoskeletal disease. 2022;14:1759720X211070205
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Mobility is an important factor for the quality of life and healthy ageing. Yet, most people as they age will experience some degree of mobility issue, typically linked to problems with joints, bones or muscles. Current medical treatments focus on the management of pain and discomfort with anti-inflammatory drugs and pain relief. However, chronic use of these medications is associated with many side effects. Olive leaf extract (OLE) is a rich source of anti-inflammatory and antioxidant compounds such as oleuropein. Animal studies of OLE showed it had promising effects on inflammation and age-related joint degeneration, and in clinical studies, it was demonstrated to preserve bone mineral density. This 6-month randomized placebo-controlled trial investigated the use of 125mg OLE on knee pain, discomfort and loss of mobility in 124 elderly subjects over 55 who experienced mild to moderate pain during or after physical activity in the absence of diagnosed underlying conditions such as osteoarthritis. The outcome was tracked by scoring questionnaires and blood samples to monitor inflammatory markers, as well as urinary samples to assess compliance. At the end of the trial, there was no significant difference in pain or inflammatory markers, apart from a decline in Prostaglandin E2 in the OLE takers. An adjusted analysis showed that whereby people with mild to moderate pain did not experience any benefits, a significant effect was seen in people who had higher levels of baseline pain to begin with. Due to the good safety profile of OLE, it may be a suitable intervention for those candidates. Larger scale trials may help to enhance these findings.
Abstract
OBJECTIVES To investigate a 6-month intervention with an olive leaf extract (OLE) on knee functionality and biomarkers of bone/cartilage metabolism and inflammation. DESIGN This randomized, double-blind, placebo-controlled, multi-centric trial included 124 subjects with knee pain or mobility issues. Subjects received twice a day one capsule of placebo or 125 mg OLE (Bonolive™, an OLE containing 50 mg of oleuropein) for 6 months. The co-primary endpoints were Knee injury and Osteoarthritis Outcome Score (KOOS) and serum Coll2-1NO2. The secondary endpoints were the subscales of the KOOS, knee pain VAS at rest and at walking, OARSI core set of performance-based tests and multiple inflammatory and bone or cartilage remodeling serum biomarkers and concentration of oleuropein's metabolites in urine. RESULTS At 6 months, OLE group was not efficient on global KOOS score, changes of inflammatory and cartilage remodeling biomarkers compared to placebo. Post hoc analyses demonstrated a large and significant treatment effect of OLE in a sub-group of subjects with high walking pain at baseline (p = 0.03). This was observed at 6 months for the global KOOS score, and each different subscale and for pain at walking (p = 0.02). OLE treatment was well tolerated. CONCLUSION OLE was not effective on joint discomfort excepted in a sub-group of subjects with high pain at treatment initiation. As oleuropein is well tolerated, OLE can be used to relieve knee joint pain and enhance mobility in subjects with articular pain.
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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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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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Plain language summary
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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Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial.
Sabico, S, Enani, MA, Sheshah, E, Aljohani, NJ, Aldisi, DA, Alotaibi, NH, Alshingetti, N, Alomar, SY, Alnaami, AM, Amer, OE, et al
Nutrients. 2021;13(7)
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Plain language summary
A highly contagious virus called SARS-CoV-2 is responsible for the Covid-19 pandemic. Vitamin D adjuvant therapy has been identified as a promising strategy for reducing the severity of Covid-19 outcomes in the elderly. Also, a low Vitamin D status significantly correlates with Covid-19 severity. This multi-centre randomised, open-label clinical trial evaluated the beneficial effects of 5000 IU versus 1000 IU Vitamin D3 daily supplementation for two weeks on recovery of symptoms in patients with mild-to-moderate Covid-19 and suboptimal Vitamin D status. Thirty-six Covid-19 patients received 5000 IU Vitamin D3 daily, and thirty-three Covid-19 patients received 1000 IU Vitamin D3 daily. The 5000 IU Vitamin D3 group was significantly younger and had a significantly lower BMI than the 1000 IU Vitamin D3 group. The 5000 IU Vitamin D3 group showed significant improvements in the severity of the Covid-19 symptoms compared to the 1000 IU Vitamin D3 group. Further robust studies are needed to evaluate the effects of Vitamin D3 supplementation in patients with high BMI, severe Covid-19 symptoms, and prevention of Covid-19. Healthcare professionals can use the results of this study to understand the effects of different doses of Vitamin D3 supplements in patients with mild-to-moderate Covid-19 symptoms and suboptimal Vitamin D status.
Abstract
OBJECTIVE Vitamin D deficiency has been associated with an increased risk of COVID-19 severity. This multi-center randomized clinical trial aims to determine the effects of 5000 IU versus 1000 IU daily oral vitamin D3 supplementation in the recovery of symptoms and other clinical parameters among mild to moderate COVID-19 patients with sub-optimal vitamin D status. STUDY DESIGN AND SETTING A total of 69 reverse transcriptase polymerase chain reaction (RT-PCR) SARS-CoV-2 positive adults who were hospitalized for mild to moderate COVID-19 disease were allocated to receive once daily for 2 weeks either 5000 IU oral vitamin D3 (n = 36, 21 males; 15 females) or 1000 IU oral vitamin D3 (standard control) (n = 33, 13 males; 20 females). Anthropometrics were measured and blood samples were taken pre- and post-supplementation. Fasting blood glucose, lipids, serum 25(OH)D, and inflammatory markers were measured. COVID-19 symptoms were noted on admission and monitored until full recovery. RESULTS Vitamin D supplementation for 2 weeks caused a significant increase in serum 25(OH)D levels in the 5000 IU group only (adjusted p = 0.003). Within-group comparisons also showed a significant decrease in BMI and IL-6 levels overtime in both groups (p-values < 0.05) but was not clinically significant in between-group comparisons. Kaplan-Meier survival analysis revealed that the 5000 IU group had a significantly shorter time to recovery (days) than the 1000 IU group in resolving cough, even after adjusting for age, sex, baseline BMI, and D-dimer (6.2 ± 0.8 versus 9.1 ± 0.8; p = 0.039), and ageusia (loss of taste) (11.4 ± 1.0 versus 16.9 ± 1.7; p = 0.035). CONCLUSION A 5000 IU daily oral vitamin D3 supplementation for 2 weeks reduces the time to recovery for cough and gustatory sensory loss among patients with sub-optimal vitamin D status and mild to moderate COVID-19 symptoms. The use of 5000 IU vitamin D3 as an adjuvant therapy for COVID-19 patients with suboptimal vitamin D status, even for a short duration, is recommended.