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Effect of Calorie Restriction and Intermittent Fasting Regimens on Brain-Derived Neurotrophic Factor Levels and Cognitive Function in Humans: A Systematic Review.
Alkurd, R, Mahrous, L, Zeb, F, Khan, MA, Alhaj, H, Khraiwesh, HM, Faris, ME
Medicina (Kaunas, Lithuania). 2024;60(1)
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Brain-derived neurotrophic factor (BDNF) is a protein that plays a crucial role in brain development, cognition and metabolism. Intermittent fasting (IF) is a promising therapeutic strategy for managing metabolic disorders and improving cognitive function. Therefore, this systematic review of sixteen experimental and observational studies investigated the effect of IF on BDNF production and improvements in cognition through the BDNF pathway in healthy adults and people with metabolic disorders. Included studies focused on different IF regimens such as calorie restriction (CR), alternate-day fasting (ADF), time-restricted eating (TRE) and Ramadan model of intermittent fasting (RIF) Future, well-controlled, long-term, robust studies are required to assess the effect of different IF regimens on the production of BDNF and cognitive function in people with metabolic disorders, as the current research is inconclusive. However, healthcare professionals can use the review to understand the potential beneficial effects of IF on cognition and metabolic health in humans.
Abstract
Background: The potential positive interaction between intermittent fasting (IF) and brain-derived neurotrophic factor (BDNF) on cognitive function has been widely discussed. This systematic review tried to assess the efficacy of interventions with different IF regimens on BDNF levels and their association with cognitive functions in humans. Interventions with different forms of IF such as caloric restriction (CR), alternate-day fasting (ADF), time-restricted eating (TRE), and the Ramadan model of intermittent fasting (RIF) were targeted. Methods: A systematic review was conducted for experimental and observational studies on healthy people and patients with diseases published in EMBASE, Scopus, PubMed, and Google Scholar databases from January 2000 to December 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statements (PRISMA) for writing this review. Results: Sixteen research works conducted on healthy people and patients with metabolic disorders met the inclusion criteria for this systematic review. Five studies showed a significant increase in BDNF after the intervention, while five studies reported a significant decrease in BDNF levels, and the other six studies showed no significant changes in BDNF levels due to IF regimens. Moreover, five studies examined the RIF protocol, of which, three studies showed a significant reduction, while two showed a significant increase in BDNF levels, along with an improvement in cognitive function after RIF. Conclusions: The current findings suggest that IF has varying effects on BDNF levels and cognitive functions in healthy, overweight/obese individuals and patients with metabolic conditions. However, few human studies have shown that IF increases BDNF levels, with controversial results. In humans, IF has yet to be fully investigated in terms of its long-term effect on BDNF and cognitive functions. Large-scale, well-controlled studies with high-quality data are warranted to elucidate the impact of the IF regimens on BDNF levels and cognitive functions.
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Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial.
Ni Lochlainn, M, Bowyer, RCE, Moll, JM, García, MP, Wadge, S, Baleanu, AF, Nessa, A, Sheedy, A, Akdag, G, Hart, D, et al
Nature communications. 2024;15(1):1859
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Humans lose skeletal muscle with advancing age, and this can progress to sarcopenia. Dietary protein is crucial for maintaining skeletal muscle health; however, several factors can lead to reduced protein intake in older age. The aim of this study was to test whether the addition of gut microbiome modulation could augment established muscle function improvements from combined protein (branched chain amino acids [BCAA]) and resistance exercise. This study was based on the PROMOTe (effect of PRebiotic and prOtein on Muscle in Older Twins) trial which was a randomised controlled trial in which twin pairs (n= 72) were randomised, one twin to each study arm. Results showed that prebiotics improved cognition but did not impact muscle strength and function, compared with placebo. Furthermore, gut microbiome modulation via prebiotic supplementation in the context of ageing-muscle research is feasible and well tolerated, with clear responses noted in the gut microbiota composition and function. Authors concluded that cheap and readily available gut microbiome interventions hold promise for improving cognitive frailty in our ageing population.
Abstract
Studies suggest that inducing gut microbiota changes may alter both muscle physiology and cognitive behaviour. Gut microbiota may play a role in both anabolic resistance of older muscle, and cognition. In this placebo controlled double blinded randomised controlled trial of 36 twin pairs (72 individuals), aged ≥60, each twin pair are block randomised to receive either placebo or prebiotic daily for 12 weeks. Resistance exercise and branched chain amino acid (BCAA) supplementation is prescribed to all participants. Outcomes are physical function and cognition. The trial is carried out remotely using video visits, online questionnaires and cognitive testing, and posting of equipment and biological samples. The prebiotic supplement is well tolerated and results in a changed gut microbiome [e.g., increased relative Bifidobacterium abundance]. There is no significant difference between prebiotic and placebo for the primary outcome of chair rise time (β = 0.579; 95% CI -1.080-2.239 p = 0.494). The prebiotic improves cognition (factor score versus placebo (β = -0.482; 95% CI,-0.813, -0.141; p = 0.014)). Our results demonstrate that cheap and readily available gut microbiome interventions may improve cognition in our ageing population. We illustrate the feasibility of remotely delivered trials for older people, which could reduce under-representation of older people in clinical trials. ClinicalTrials.gov registration: NCT04309292.
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A multidomain intervention against cognitive decline in an at-risk-population in Germany: Results from the cluster-randomized AgeWell.de trial.
Zülke, AE, Pabst, A, Luppa, M, Roehr, S, Seidling, H, Oey, A, Cardona, MI, Blotenberg, I, Bauer, A, Weise, S, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024;20(1):615-628
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Due to ageing populations, there is a rapid increase in people living with dementia. A number of modifiable risk factors have been identified, including obesity, excessive alcohol consumption, diabetes mellitus, depression, physical inactivity, smoking and social isolation. The aim of this cluster-randomised controlled trial, including 1030 participants at risk of developing dementia aged 60-77, was to evaluate the effectiveness of a multidomain intervention which included optimisation of nutrition and medication, and physical, social, and cognitive activity for two years compared to standard care. There was no benefit of the intervention for the primary outcome global cognitive performance. The intervention had a positive effect on the secondary outcome health-related quality of life but did not have any significant effect on quality of life, depressive symptoms, social inclusion, activities of daily living and instrumental activities of daily living. The study period coincided with the COVID-19 pandemic. Significantly more participants than controls reported perceived COVID-19-related restrictions with regards to nutrition, whilst there was no such differences between groups for physical, cognitive or social activity. Better adherence to the nutrition and social activity components of the programme were associated with better global cognitive performance, whilst there was no association with physical and cognitive activity.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Nutrition counselling based on the guidelines of the German Society for Nutrition, in association with other lifestyle counselling and optimisation of medication, does not improve GCP.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
The aim of this study was to evaluate the effectiveness of the AgeWell.de programme which targets modifiable risk factors for dementia.
Methods
- Cluster-randomised, controlled trial (clustered by participating general practitioners).
- Intervention: nutritional counselling (based on the guidelines by the German Society for Nutrition), enhancement of physical and social activity, cognitive training, and the management of cardiovascular risk factors (overweight, smoking). Baseline individual face-to-face session with study nurse, followed by contact with the nurse after 2, 4 and 8 months, second face-to-face session with the nurse at 12 months and further contacts at 16 and 20 months. Endpoint assessments at 24 months.
- Controls: standard care.
- Sample size: 1030 adults aged 60-77 at increased risk of dementia, of which 819 completed the study and were included in the analysis.
- Primary outcome: global cognitive performance (GCP)
- Secondary outcomes: mortality, nursing home placement, activities of daily living (ADL), instrumental activities of daily living (IADL), quality of life (QOL), health-related (QOL), depressive symptoms, and social inclusion.
Results
- No significant difference in GCP, p=0.874. No difference in ADL (p=0.374), IADL (p=0.746), QOL (p=0.964), depressive symptoms (p=0.090) and social inclusion (p=0.495).
- Improvement in health-related QOL (AME = 0.198, 95% CI: 0.069, 0.328, p=0.003).
- Results for mortality and nursing home placement are not reported.
- Part of the study took place during the COVID-19 pandemic. More participants (9%) than controls (3.7%) reported perceived COVID-19-related restrictions with regards to nutrition (p=0.004). No such difference was observed for perceived restrictions regarding physical activity (p=0.328), cognitive activity (p=0.262) or social activity (p=0.192).
Conclusion
- The authors concluded that the multidomain intervention had no beneficial effects on GCP and that higher-intensity interventions and more ambitious goals may be needed.
Clinical practice applications:
- Nutrition counselling based on the guidelines of the German Society for Nutrition, in association with other lifestyle counselling and optimisation of medication, does not improve GCP.
Considerations for future research:
- Studies using more intensive and individualised interventions may evaluate whether such strategies are more beneficial for improving GCP.
- Studies of specific subgroups, e.g. based on lifestyle or medical risk factors, may help find more specific populations and interventions to help improve GCP.
Abstract
INTRODUCTION We investigated the effectiveness of a multidomain intervention to preserve cognitive function in older adults at risk for dementia in Germany in a cluster-randomized trial. METHODS Individuals with a Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk score ≥ 9 aged 60 to 77 years were recruited. After randomization of their general practitioner (GP), patients received a multidomain intervention (including optimization of nutrition and medication, and physical, social, and cognitive activity) or general health advice and GP treatment as usual over 24 months. Primary outcome was global cognitive performance (composite z score, based on domain-specific neuropsychological tests). RESULTS Of 1030 participants at baseline, n = 819 completed the 24-month follow-up assessment. No differences regarding global cognitive performance (average marginal effect = 0.010, 95% confidence interval: -0.113, 0.133) were found between groups at follow-up. Perceived restrictions in intervention conduct by the COVID-19 pandemic did not impact intervention effectiveness. DISCUSSION The intervention did not improve global cognitive performance. HIGHLIGHTS Overall, no intervention effects on global cognitive performance were detected. The multidomain intervention improved health-related quality of life in the total sample. In women, the multidomain intervention reduced depressive symptoms. The intervention was completed during the COVID-19 pandemic.
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Mediterranean diet and structural neuroimaging biomarkers of Alzheimer's and cerebrovascular disease: A systematic review.
Gregory, S, Pullen, H, Ritchie, CW, Shannon, OM, Stevenson, EJ, Muniz-Terrera, G
Experimental gerontology. 2023;172:112065
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Nearly a million people in the UK have Alzheimer's disease, the most common type of dementia. Mediterranean diet (MedDiet) adherence is associated with healthy brain ageing, a reduced stroke risk, and a lower incidence of dementia. Seven studies were included in this review to evaluate the effects of MedDiet on hippocampal volume and white matter hyperintensity volume, predictors of stroke and dementia. This systematic review did not reveal any associations between MedDiet adherence and hippocampal volume. However, there was a significant negative relationship between MedDiet adherence and white matter hyperintensity volume in two of the studies included. It is necessary to conduct more robust studies to investigate the associations between MedDiet adherence and structural brain imaging findings and understand the mechanisms behind dementia and other cerebrovascular diseases. This study could provide healthcare professionals with valuable information about the effects of increased MedDiet adherence on brain health, including its potential to delay neurodegenerative disease progression.
Expert Review
Conflicts of interest:
None
Take Home Message:
Due to inconclusive results on the associations between MedDiet adherence and AD and cerebrovascular related structural neuroimaging findings, specific recommendations for the MedDiet cannot be made on the basis of this study until further research has been completed.
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:
Background:
Changes in hippocampal volume (HV) and white matter intensity volume (WMIV) have been identified as structural neuroimaging biomarkers of neurodegenerative disease such as Alzheimer’s Disease (AD) and Cerebrovascular disease (CVD) respectively. Evidence has shown adherence to the Mediterranean Diet (MedDiet) has been associated with reduced risk for strokes. This review evaluated the MedDiet in relation to HV and WMIV.
Methods:
The review followed PRISMA guidelines and was registered on PROSPERO. Literature searching resulted in seven studies published between 2012 and 2022, which met the inclusion criteria. Six studies analysed cross-sectional data and one analysed longitudinal data. The NIH Quality Assessment Tool for Observational and Cross-Sectional Studies was used to assess risk of bias.
Overall, the studies were rated as low-risk of bias with details of the research question, participant group exposure and outcome variables included. Due to moderate to high heterogeneity in some studies, a meta-analysis was deemed unsuitable and narrative synthesis was conducted to present the results.
Results:
Mean participant age ranged from 53.19 to 80.3 years and volunteers were healthy or had subjective cognitive decline and a few participants had dementia (n=46).
Hippocampal Volume:
Four studies included 20,077 participants and found no significant associations between MedDiet adherence and hippocampal volume. All four studies were cross-sectional from larger cohort studies. To establish causative relationships longitudinal and RCT trials are required.
White Matter Hyperintensity Volumes:
Four studies included 1938 participants. Two studies found a significant negative association between MedDiet and WMHV, demonstrating higher Mediterranean Scores were associated with lower level of WHMV. The other two studies found no significant associations.
Although the review methodology with a piloted search strategy was considered a key strength, the lack of meta-analysis as planned in the a priori protocol, due to minimal eligible studies and high heterogeneity was a limitation as well as the restriction of brain imaging outcomes.
Conclusion:
Overall, these results are inconclusive on the associations between the MedDiet and HV and WMHV, and identify a gap in the knowledge, therefore further research such as RCT’s remains a priority to further understand the impact diet may have on neuroimaging markers of AD and CVD.
Clinical practice applications:
There were no significant associations between MedDiet adherence and HV, which was surprising given the evidence stating adherence to the MedDiet is associated with a lower incidence of dementia and stroke. However all four studies were cross-sectional studies and in order to detect causal associations, longitudinal and RCT’s are needed. Two studies did show a significant association between higher MedDiet adherence and lower WMHV, whereas two studies reported no significant associations.
Caution needs to be taken when recommending the MedDiet specifically for a reduction in HV and WMHV until further research has been undertaken.
Considerations for future research:
Future research should consider:
- larger cohorts and participants from the Mediterranean region where lifelong adherence to the MedDiet is more likely.
- looking at other risk factors to include obesity, lack of activity, poor sleep quality and stress.
- evaluating different socio-economic status, which has been shown to impact dietary behaviour.
- alternative imaging outcomes such as cortical thinning, PET amyloid and tau.
- . gold standard for methodology in particular dietary analysis and scanning and outcome derivation.
Abstract
Previous studies have demonstrated an association between adherence to the Mediterranean diet (MedDiet) and better cognitive performance, lower incidence of dementia and lower Alzheimer's disease biomarker burden. The aim of this systematic review was to evaluate the evidence base for MedDiet associations with hippocampal volume and white matter hyperintensity volume (WMHV). We searched systematically for studies reporting on MedDiet and hippocampal volume or WMHV in MedLine, EMBASE, CINAHL and PsycInfo. Searches were initially carried out on 21st July 2021 with final searches run on 23rd November 2022. Risk of bias was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Of an initial 112 papers identified, seven papers were eligible for inclusion in the review reporting on 21,933 participants. Four studies reported on hippocampal volume, with inconclusive or no associations seen with MedDiet adherence. Two studies found a significant association between higher MedDiet adherence and lower WMHV, while two other studies found no significant associations. Overall these results highlight a gap in our knowledge about the associations between the MedDiet and AD and cerebrovascular related structural neuroimaging findings.
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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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X
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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A Randomised Placebo-Controlled Study of Purified Anthocyanins on Cognition in Individuals at Increased Risk for Dementia.
Aarsland, D, Khalifa, K, Bergland, AK, Soennesyn, H, Oppedal, K, Holteng, LBA, Oesterhus, R, Nakling, A, Jarholm, JA, de Lucia, C, et al
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. 2023;31(2):141-151
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A growing body of evidence suggests that some modifiable factors, including cardiometabolic disorders such as hypertension, diabetes and hypercholesterolemia, as well as lifestyle factors such as physical exercise and diet, are associated with an increased risk of developing dementia. Anthocyanins, a flavonoid subclass found in dark berries and fruits, are among the dietary factors that may have positive effects on the pathogenesis of Alzheimer’s disease. The aim of this study was to assess whether anthocyanins can improve cognition and reduce the risk of dementia. This study is a 24-week randomised, double-blind, placebo-controlled Phase II study. Two-hundred and six participants were randomly assigned to one of the two groups: anthocyanins (n=106) or placebo (n=100). Results show that there wasn’t any significant group difference at the end of the study (24 weeks) in episodic memory (primary analysis) or for the secondary cognitive outcomes. However, there was a significant difference in slopes during weeks 8−24 where the anthocyanin group improved while the placebo group worsened. Furthermore, anthocyanin capsules were well-tolerated and safe to use. Authors conclude that future studies need to explore the potential mechanisms leading to cognitive improvement, how they relate to bioavailability of anthocyanins and metabolites, the optimal dosage, and the duration of treatment.
Abstract
IMPORTANCE Identifying nutritional compounds which can reduce cognitive decline in older people is a hugely important topic. OBJECTIVE To study the safety and effect of anthocyanins in maintaining cognitive functioning in people at increased risk for dementia. DESIGN, SETTING, AND PARTICIPANTS Participants (206 individuals, aged 60-80 years) diagnosed with either mild cognitive impairment (MCI) or two or more cardiometabolic disorders (i.e., diabetes, hypertension, obesity) were enrolled at three different centres in Norway. INTERVENTION Participants were randomly assigned to four capsules with a total of 320 mg/d of naturally purified anthocyanins or placebo 1:1 for 24 weeks. MAIN OUTCOMES AND MEASURES The primary outcome was the Quality of Episodic Memory composite measure (0-100) from an online cognitive test battery CogTrack, which was administered at baseline and monthly for the next 24 weeks. Secondary outcomes included other cognitive scores from the CogTrack battery. We applied mixed effects models with a baseline test score, group, time and their interaction as fixed effects, as well as other predefined baseline covariates. The primary comparison was the group difference at week 24 based on a modified intention-to-treat principle. RESULTS The primary analysis did not show a significant group difference at 24 weeks (78.2 versus 76.8; adjusted mean difference 1.4 (95% confidence interval -0.9-3.7); effect size 0.15; p = 0.23). However, there was a significant difference in slopes during weeks 8-24 (p = 0.007); the anthocyanin group improved while the placebo group worsened. No differences were found for the secondary cognitive outcomes. Anthocyanin capsules were well-tolerated and safe to use. CONCLUSION Anthocyanin supplementation for 24 weeks was safe and well tolerated in people with MCI or cardiometabolic disorders. We found no significant group difference in episodic memory at the end of the study but statistically significant differences in slopes. Further studies are warranted to explore whether anthocyanins supplementation can reduce cognitive decline in people at increased risk of dementia. TRIAL REGISTRATION ClinicalTrials.gov, (Identifier NCT03419039). http://www. CLINICALTRIALS gov/, NCT03419039.
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Insufficient sleep predicts poor weight loss maintenance after 1 year.
Bogh, AF, Jensen, SBK, Juhl, CR, Janus, C, Sandsdal, RM, Lundgren, JR, Noer, MH, Vu, NQ, Fiorenza, M, Stallknecht, BM, et al
Sleep. 2023;46(5)
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Short sleep duration, defined as less than 6 hours/night, is associated with all-cause mortality, cardiovascular diseases, hypertension, diabetes, and obesity. Sleep restriction causes metabolic and behavioural changes suggesting that short sleep duration may contribute to the development of obesity. The aim of this study was to investigate associations between short sleep duration or poor sleep quality and weight regain after weight loss. This study is based on data from the S-LiTE randomised, controlled trial. Participants followed a low-calorie diet (800 kcal/day) for eight weeks prior to randomisation. Those who lost at least 5% of initial weight were randomised to the control or intervention group. Results showed that participants with objectively measured short sleep duration after a diet-induced weight loss had less success during weight loss maintenance than those with longer sleep duration. Worse sleep quality was associated with less weight loss during a low-calorie diet and subsequent weight maintenance. Authors conclude that insufficient sleep predicts weight regain during interventional efforts to maintain weight loss. Exercise maintained low-calorie diet-induced improvements in sleep quality during 1 year of weight loss maintenance, and liraglutide transiently increased sleep duration.
Abstract
STUDY OBJECTIVES Insufficient sleep may attenuate weight loss, but the role of sleep in weight loss maintenance is unknown. Since weight regain after weight loss remains a major obstacle in obesity treatment, we investigated whether insufficient sleep predicts weight regain during weight loss maintenance. METHODS In a randomized, controlled, two-by-two factorial study, 195 adults with obesity completed an 8-week low-calorie diet and were randomly assigned to 1-year weight loss maintenance with or without exercise and liraglutide 3.0 mg/day or placebo. Sleep duration and quality were measured before and after the low-calorie diet and during weight maintenance using wrist-worn accelerometers (GENEActiv) and Pittsburgh Sleep Quality Index (PSQI). To test associations between insufficient sleep and weight regain, participants were stratified at randomization into subgroups according to sleep duration (≥6 h/night) or sleep quality (PSQI score ≤/>5). RESULTS After a diet-induced 13.1 kg weight loss, participants with short sleep duration at randomization regained 5.3 kg body weight (p = .0008) and had less reduction in body fat percentage compared with participants with normal sleep duration (p = .007) during the 1-year weight maintenance phase. Participants with poor sleep quality before the weight loss regained 3.5 kg body weight compared with good quality sleepers (p = .010). During the weight maintenance phase, participants undergoing liraglutide treatment displayed increased sleep duration compared with placebo after 26 weeks (5 vs. -15 min/night) but not after 1 year. Participants undergoing exercise treatment preserved the sleep quality improvements attained from the initial weight loss. CONCLUSIONS Short sleep duration or poor sleep quality was associated with weight regain after weight loss in adults with obesity.
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Probiotic intervention benefits multiple neural behaviors in older adults with mild cognitive impairment.
Fei, Y, Wang, R, Lu, J, Peng, S, Yang, S, Wang, Y, Zheng, K, Li, R, Lin, L, Li, M
Geriatric nursing (New York, N.Y.). 2023;51:167-175
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Mild cognitive impairment (MCI) is an intermediate stage between the normal cognitive changes associated with aging and dementia. Recent research shows that probiotic supplementation can regulate the balance of the intestinal flora and improve self-care ability and cognition in older adults. The aim of this study was to explore the effects and the underlying mechanisms of probiotic supplementation on MCI older adults. This study was a pilot randomised controlled trial (RCT) to investigate the effects of 12 weeks of probiotic supplementation in patients with MCI. Participants were randomly assigned to the probiotic group or control group. Results demonstrated the beneficial effects of probiotic supplementation intervention on multiple neural behaviours by regulating the homeostasis of the gut microbiota in older MCI patients. Authors conclude that this study provided new insights into nutrition interventions in older MCI patients. However, further trials with larger cohorts should be conducted to confirm the effects of probiotic intervention in MCI patients and provide more clinical evidence for its preventive and therapeutic effects.
Abstract
Probiotic supplements were shown to improve cognitive function in Alzheimer's disease (AD) patients. However, it is still unclear whether this applies to older individuals with mild cognitive impairment (MCI). We aimed to explore the effects of probiotic supplementation on multiple neural behaviors in older adults with MCI. Forty-two MCI patients (age > 60 years) were randomly divided into two groups and consumed either probiotics (n=21) or placebo (n=21) for 12 weeks. Various scale scores, gut microbiota measures and serological indicators were recorded pre- and posttreatment. After 12 weeks of intervention, cognitive function and sleep quality were improved in the probiotic group compared with those in the control group, and the underlying mechanisms were associated with changes in the intestinal microbiota. In conclusion, our study demonstrated that probiotic treatment enhanced cognitive function and sleep quality in older MCI patients, thus providing important insights into the clinical prevention and treatment of MCI.
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Psychobiotic Effects on Anxiety Are Modulated by Lifestyle Behaviors: A Randomized Placebo-Controlled Trial on Healthy Adults.
Morales-Torres, R, Carrasco-Gubernatis, C, Grasso-Cladera, A, Cosmelli, D, Parada, FJ, Palacios-García, I
Nutrients. 2023;15(7)
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The microbiota-gut-brain axis refers to the complex communication system between the human gastrointestinal tract, the micro-organisms which inhabit it, and the peripheral and central nervous systems. In recent years, human trials have linked the microbiome with specific processes that are expected to contribute to well-being. The aim of this study was to assess the effect of a psychobiotic formulation specifically on well-being, exploring the extent to which these effects might be modulated by lifestyle factors such as diet, physical activity, social connectedness, and others. This study was a four week, double-blind, randomised, placebo-controlled trial. Participants were randomised into one of two groups; placebo or probiotic group. Results showed that there were no significant effects of probiotics on a set of psychological measures of well-being. However, further analysis revealed that healthy lifestyle behaviours were significantly correlated with wellbeing across scales. Authors conclude that their findings demonstrate the need of controlling lifestyle variables as a standard practice in human microbiome research and mental health research in general.
Abstract
Psychobiotics are modulators of the Microbiota-Gut-Brain Axis (MGBA) with promising benefits to mental health. Lifestyle behaviors are established modulators of both mental health and the MGBA. This randomized placebo-controlled clinical trial (NCT04823533) on healthy adults (N = 135) tested 4 weeks of probiotic supplementation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175). We assessed effects on wellbeing, quality of life, emotional regulation, anxiety, mindfulness and interoceptive awareness. We then analyzed if lifestyle behaviors modulated probiotic effectiveness. Results showed no significant effects of probiotic intake in whole sample outcomes. Correlational analyses revealed Healthy Behaviors were significantly correlated with wellbeing across scales. Moreover, the linear mixed-effects model showed that the interaction between high scores in Healthy Behaviors and probiotic intake was the single significant predictor of positive effects on anxiety, emotional regulation, and mindfulness in post-treatment outcomes. These findings highlight the relevance of controlling for lifestyle behaviors in psychobiotic and mental health research.
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PRO-DEMET Randomized Controlled Trial on Probiotics in Depression-Pilot Study Results.
Gawlik-Kotelnicka, O, Margulska, A, Skowrońska, A, Strzelecki, D
Nutrients. 2023;15(6)
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Depression often coexists with metabolic abnormalities, and metabolic syndrome (MetS) is diagnosed in 30% of depressed subjects. Importantly, both obesity and MetS have been found to be independently associated with depressive symptoms and inflammation. The aim of this study was to investigate the effect of probiotics in the treatment of depressive disorders with possible comorbid MetS and its components. This study was an internal feasibility study based on the main randomised study - a single-centre, parallel-group, prospective, randomised, double-blind, placebo-controlled pilot trial. Adult patients (≥18 years) with depressive disorders were randomly assigned (1:1) into either the placebo or probiotic group. Results showed a positive association between probiotics supplementation and psychometric parameters together with the metabolic profile, serum inflammation markers, and biomarkers of metabolic-associated fatty liver disease in patients with depressive disorders. Authors conclude that the findings of their study would be suitable for determining the potential clinical use of probiotics and assessing certain key factors such as potential biomarkers of response.
Abstract
There is a pressing need to identify new treatment options for depression and its comorbidities. Depression often coexists with metabolic complications, and the two may share a pathophysiological overlap, including inflammation and microbiota changes. Microbiota interventions (e.g., probiotics) may represent a safe and easy-to-use treatment option as an adjunctive therapy in patients only partially responsive to pharmacologic treatment. (1) Objective: The paper presents the results of a feasibility and pilot study. The study is an internal part of a randomized controlled trail (RCT) of the effect of probiotic supplementation on psychometric, anthropometric, metabolic, and inflammatory parameters in adult patients with depressive disorders depending on the presence of metabolic syndrome. (2) Methods: The trial has a four-arm, parallel-group, prospective, randomized, double-blind, controlled design. Sixty participants received a probiotic preparation containing Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175 over 60 days. The feasibility of the study design was assessed, as well as the rates of recruitment, eligibility, consent, and study completion. The following were assessed: depressive, anxiety and stress symptoms, quality of life, blood pressure, body mass index and waist circumference, complete blood count with differential, serum levels of C-reactive protein, high-density lipoprotein cholesterol, triglycerides, fasting glucose, some secondary markers of inflammation and metabolic health, as well as noninvasive biomarkers of liver fibrosis (APRI and FIB-4). (3) Results: The study was found to be generally feasible. The eligibility rate was 52% of recruited participants with 80% completing the study protocol. No differences in sociodemographic or anthropometric factors or basic laboratory findings were found between the placebo and probiotic group at the start of the intervention period. Importantly, the proportion of recruited participants fulfilling the criteria of metabolic syndrome was too low. (4) Conclusions: Whilst the whole study protocol was feasible, some different timepoint procedures require modification. The major weakness of the recruitment methods was that the percentage of metabolic arms participants was insufficient. Overall, the full RCT design on probiotics in depression with vs. without metabolic syndrome was shown to be feasible with little modification.