1.
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).
2.
How to reduce brain inflammation: 4 actions you can take today
Dr Ruscio is a Doctor of Natural Medicine, Doctor of Chiropractic, clinical researcher and author. His podcast, Dr Ruscio Radio presents cutting edge information in health, nutrition and functional medicine distilled into practical advice that can be used to improve our health.
2023
Abstract
Dr Ruscio focuses on the link between brain inflammation and neurodegenerative diseases such as Alzheimer’s and Parkinson’s but also brain fog and mood. He summarises how it might be possible to reduce neuroinflammation through diet, looking at the links with dysbiosis and leaky gut but also exercise, sleep hygiene, and stress management. A concise overview of the evidence for diets such as Paleo, Low FODMAP, Ketogenic and Low Carb, as well as the Mediterranean diet for reducing inflammation and supporting brain health is provided. The potential for lab testing via anti and pro-inflammatory markers is also reviewed.
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Gut microbial metabolites in depression: understanding the biochemical mechanisms.
Caspani, G, Kennedy, S, Foster, JA, Swann, J
Microbial cell (Graz, Austria). 2019;6(10):454-481
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Major depressive disorder is a leading cause of disability and is linked to shortened life expectancy and suicide. Despite its prevalence, for near to a third of patients, long-term treatment options are ineffective. In addition to the primary presentation of persistent low mood, other emotional and physiological symptoms, researchers have also identified alterations in metabolism, hormones and the immune system. Furthermore, increasing evidence suggests that depression and depressive behaviour is also influenced by divergences in gut health and gut bacteria composition. With insights from animal and human research, this review highlights how the gut and gut bacteria-derived metabolites can directly or indirectly influence mood. Described are the pathways of how the gut and its microorganism communicate with the brain, the essential role the immune system has as part of the gut-brain communication, and the impact of low-grade, chronic inflammation on neurofunction. Comprehensive summaries are dedicated to how several metabolites or by-products from gut bacteria can influence the nervous system and gene expression in relation to depression. These include substances like neurotransmitters, short-chain fatty acids, tryptophan metabolites, lactate, bile acids, choline metabolites and folate. This article yields a detailed overview of how gut health and microbiota can influence neurofunction and mental health. The authors promote the idea of the gut as a suitable target for the management of depressive disorders, whilst also eluding to the current limitations and need for further research.
Abstract
Gastrointestinal and central function are intrinsically connected by the gut microbiota, an ecosystem that has co-evolved with the host to expand its biotransformational capabilities and interact with host physiological processes by means of its metabolic products. Abnormalities in this microbiota-gut-brain axis have emerged as a key component in the pathophysiology of depression, leading to more research attempting to understand the neuroactive potential of the products of gut microbial metabolism. This review explores the potential for the gut microbiota to contribute to depression and focuses on the role that microbially-derived molecules - neurotransmitters, short-chain fatty acids, indoles, bile acids, choline metabolites, lactate and vitamins - play in the context of emotional behavior. The future of gut-brain axis research lies is moving away from association, towards the mechanisms underlying the relationship between the gut bacteria and depressive behavior. We propose that direct and indirect mechanisms exist through which gut microbial metabolites affect depressive behavior: these include (i) direct stimulation of central receptors, (ii) peripheral stimulation of neural, endocrine, and immune mediators, and (iii) epigenetic regulation of histone acetylation and DNA methylation. Elucidating these mechanisms is essential to expand our understanding of the etiology of depression, and to develop new strategies to harness the beneficial psychotropic effects of these molecules. Overall, the review highlights the potential for dietary interventions to represent such novel therapeutic strategies for major depressive disorder.
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Efficacy and Safety of Lactobacillus Plantarum C29-Fermented Soybean (DW2009) in Individuals with Mild Cognitive Impairment: A 12-Week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.
Hwang, YH, Park, S, Paik, JW, Chae, SW, Kim, DH, Jeong, DG, Ha, E, Kim, M, Hong, G, Park, SH, et al
Nutrients. 2019;11(2)
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Mild cognitive impairment (MCI) describes a range of symptoms that impact on cognition and memory, but not to such an extent that it seriously affects a person's day to day life. People with MCI are at higher risk of going on to develop dementia. Consumption of both probiotics and soy beans have been shown to enhance memory function in previous studies on animals and humans. In this Korean study, a randomised, double-blind, placebo-controlled trial, researchers used soybeans that had been fermented with a bacterium called Lactobacillus plantarum C29, a type of bacteria which is found in the traditional Korean food kimchi. One hundred men and women diagnosed with MCI were given capsules containing either 800 mg of dried fermented soybeans or a placebo for 12 weeks. Participants underwent a series of memory and attention tests to measure cognitive function. Researchers also looked at levels of a protein that supports nerve cells, called brain-derived neurotropic factor (BDNF) in the blood, as well as the composition of bacteria in the stool samples of the participants. The group that consumed the fermented soybeans showed greater improvements in the overall cognitive function, especially attention, compared to those who took the placebo. BDNF levels increased in the soybean group but declined in the placebo group. Increases in BDNF were associated with improvements in cognitive function. The results of this clinical trial suggest that fermented soybeans can be safely consumed by people with MCI to enhance cognitive function. The authors suggested that the increase in blood BDNF levels may be partly responsible for the improved cognitive function, and this in turn points to the importance of the so-called gut-brain axis in improving symptoms of MCI.
Abstract
Early intervention using dietary supplements may be effective in alleviating cognitive impairment among individuals with mild cognitive impairment (MCI). This study investigated the efficacy and safety of Lactobacillus plantarum C29-fermented soybean (DW2009) as a nutritional supplement for cognitive enhancement. One hundred individuals with MCI were randomly assigned to take DW2009 (800 mg/day, n = 50) or placebo (800 mg/day, n = 50) for 12 weeks. The primary outcome measure was change in the composite score of cognitive functions related to memory and attention, measured by computerized neurocognitive function tests. Associations between changes in serum brain-derived neurotrophic factor (BDNF) levels and cognitive performance for each treatment group were evaluated. Compared to the placebo group, the DW2009 group showed greater improvements in the combined cognitive functions (z = 2.36, p for interaction = 0.02), especially in the attention domain (z = 2.34, p for interaction = 0.02). Cognitive improvement was associated with increased serum BDNF levels after consumption of DW2009 (t = 2.83, p = 0.007). The results of this clinical trial suggest that DW2009 can be safely administered to enhance cognitive function in individuals with MCI. Increased serum BDNF levels after administering DW2009 may provide preliminary insight into the underlying effects of cognitive improvement, which suggests the importance of the gut-brain axis in ameliorating cognitive deficits in MCI.