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Absence of Effects of L-Arginine and L-Citrulline on Inflammatory Biomarkers and Oxidative Stress in Response to Physical Exercise: A Systematic Review with Meta-Analysis.
Porto, AA, Gonzaga, LA, Benjamim, CJR, Valenti, VE
Nutrients. 2023;15(8)
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L-citrulline is a non-essential amino acid that acts as a precursor to L-arginine. L-arginine is a semi-essential amino acid used for nitric oxide production which is crucial for maintaining physiological function and immune regulation. Previous research has shown that L-citrulline and L-arginine supplementation may offer antioxidant and anti-inflammatory benefits in reducing exercise-related oxidative stress and inflammation. This systematic review and meta-analysis included seven randomised controlled trials to investigate the effect of L-citrulline and L-arginine on antioxidants, oxidative stress, and inflammatory and anti-inflammatory markers. This systematic review and meta-analysis showed no significant improvements in oxidative stress and inflammation followed by the supplementation of L-citrulline and L-arginine before exercise. However, further robust studies that include different dosages and exercise intensities are required to assess the beneficial effects of L-citrulline and L-arginine supplements to support physical exercise-induced oxidative stress and inflammation due to the heterogeneity of the included studies. Healthcare professionals can use the results of this study to understand the potential benefits of L-citrulline and L-arginine supplementation in people prone to producing proinflammatory cytokines.
Abstract
The repercussions on oxidative and inflammatory stress markers under the effects of arginine and citrulline in response to exercise are not fully reached. We completed a systematic review to investigate the effects of L-Citrulline or L-Arginine on oxidative stress and inflammatory biomarkers following exercise. EMBASE, MEDLINE (PubMed), Cochrane Library, CINAHL, LILACS, and Web of Science databases were used to record the trials. This study includes randomized controlled trials (RCTs) and non-RCTs with subjects over 18 years old. Those under the intervention protocol consumed L-Citrulline or L-Arginine, and the controls ingested placebo. We recognized 1080 studies, but only 7 were included (7 studies in meta-analysis). We observed no difference between pre- vs. post-exercise for oxidative stress (subtotal = -0.21 [CI: -0.56, 0.14], p = 0.24, and heterogeneity = 0%. In the sub-group "L-Arginine" we found a subtotal = -0.29 [-0.71, 0.12], p = 0.16, and heterogeneity = 0%. For the "L-Citrulline" subgroup we observed a subtotal = 0.00 [-0.67, 0.67], p = 1.00, and heterogeneity was not applicable. No differences were observed between groups (p = 0.47), and I² = 0%) or in antioxidant activity (subtotal = -0.28 [-1.65, 1.08], p = 0.68, and heterogeneity = 0%). In the "L-Arginine" sub-group, we found a subtotal = -3.90 [-14.18, 6.38], p = 0.46, and heterogeneity was not applicable. For the "L-Citrulline" subgroup, we reported a subtotal = -0.22 [-1.60, 1.16], p = 0.75, and heterogeneity was not applicable. No differences were observed between groups (p = 0.49), and I² = 0%), inflammatory markers (subtotal = 8.38 [-0.02, 16.78], p = 0.05, and heterogeneity = 93%. Tests for subgroup differences were not applicable, and anti-inflammatory markers (subtotal = -0.38 [-1.15, 0.39], p = 0.34 and heterogeneity = 15%; testing for subgroup differences was not applicable). In conclusion, our systematic review and meta-analysis found that L-Citrulline and L-Arginine did not influence inflammatory biomarkers and oxidative stress after exercise.
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Do Dietary Supplements Affect Inflammation, Oxidative Stress, and Antioxidant Status in Adults with Hypothyroidism or Hashimoto's Disease?-A Systematic Review of Controlled Trials.
Kubiak, K, Szmidt, MK, Kaluza, J, Zylka, A, Sicinska, E
Antioxidants (Basel, Switzerland). 2023;12(10)
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A deficiency of the thyroid hormone causes hypothyroidism (HT), whereas Autoimmune thyroiditis (AIT) is mainly an organ-specific autoimmune condition. Both HT and AIT are characterised by low-grade inflammation and inflammation in the thyroid gland. Dietary supplements may offer health benefits; however, previous research findings are inconclusive. This systematic review evaluated twenty-two controlled studies to understand the effectiveness of dietary supplements in reducing inflammation and oxidative stress and improving antioxidant and thyroid parameters in patients with HT or AIT. The efficacy of dietary supplements in improving thyroid health and reducing inflammation and oxidative stress was inconclusive due to the low quality of the included studies and the limited number of available studies. Selenium supplements might be beneficial in improving thyroid parameters and inflammation in patients with HT or AIT. Even though the therapeutic benefits of dietary supplements in treating thyroid disease were inconclusive, healthcare professionals can use them to address the common nutritional deficiencies in people with HT and AIT. Further, large, long-term, robust studies are required to assess the therapeutic utility of different dietary supplements in promoting the health of the thyroid gland.
Abstract
This systematic review aims to summarise the results of controlled trials on dietary supplements (DS) usage and inflammation, oxidative stress, antioxidant status, and thyroid parameter improvement in hypothyroidism (HT)/Hashimoto's thyroiditis (AIT) patients. The study protocol was registered with PROSPERO (no. CRD42022365149). A comprehensive search of the PubMed, Scopus, and Web of Science databases resulted in the identification of nineteen randomised controlled trials and three non-randomised studies for the review; three studies examined the effect of supplementation with vitamin D, twelve studies-with selenium, and seven studies-with other DS. Based on very limited evidence, the lack of influence of vitamin D supplementation on inflammatory parameters was found, while no studies have examined oxidative stress and antioxidant status parameters, and only one provided results for a single thyroid parameter after an intervention. Some evidence was found proving that selenium supplementation may decrease inflammation and improve thyroid parameters, but reaching a conclusion about its influence on oxidative stress and antioxidant status is not possible because of the insufficient number of studies. Additionally, due to examining other DS (e.g., multicomponent, Nigella sativa, and genistein) only in single studies, conclusions cannot be drawn. Further long-term, high-quality randomised controlled trials are necessary to better understand the influence of DS on inflammation, oxidative stress, and antioxidant status, as well as their potential to improve thyroid gland function in HT/AIT patients.
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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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Effect of Dietary Intervention, with or without Cointerventions, on Inflammatory Markers in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.
Hall, RL, George, ES, Tierney, AC, Reddy, AJ
Advances in nutrition (Bethesda, Md.). 2023;14(3):475-499
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Multiple factors, including toxic accumulation of fatty acids in adipose tissue; impaired microbial functioning of the gut; and an imbalance of inflammatory mediators, contribute to a progressed inflammatory state in the liver. The aim of this study was to assess the cumulative effect of evidence regarding the effect of dietary intervention, with or without cointerventions, on the inflammatory profile of adults diagnosed with non-alcoholic fatty liver disease (NAFLD). This study was a systematic review and meta-analysis of forty-four randomised controlled trials. A total of 2579 participants with NAFLD were enrolled in the studies, of whom 2497 participants were analysed. Results (meta-analysis) showed that a hypocaloric diet, when used alone or with supplementation, was the most effective dietary intervention for the improvement of NAFLD-implicated inflammatory markers, adiponectin, and leptin. Whereas isocaloric or energy-balanced dietary interventions provided improvements to the same inflammatory cytokines and adipokines when coupled with supplementation but the benefit was less. Authors conclude that larger sample sizes and longer duration studies are needed in order to better determine the effectiveness of dietary intervention on a NAFLD population.
Abstract
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease from simple steatosis to nonalcoholic steatohepatitis, with inflammatory cytokines and adipokines identified as drivers of disease progression. Poor dietary patterns are known to promote an inflammatory milieu, although the effects of specific diets remain largely unknown. This review aimed to gather and summarize new and existing evidence on the effect of dietary intervention on inflammatory markers in patients with NAFLD. The electronic databases MEDLINE, EMBASE, CINAHL, and Cochrane were searched for clinical trials which investigated outcomes of inflammatory cytokines and adipokines. Eligible studies included adults >18 y with NAFLD, which compared a dietary intervention with an alternative diet or control (no intervention) group or were accompanied by supplementation or other lifestyle interventions. Outcomes for inflammatory markers were grouped and pooled for meta-analysis where heterogeneity was allowed. Methodological quality and risk of bias were assessed using the Academy of Nutrition and Dietetics Criteria. Overall, 44 studies with a total of 2579 participants were included. Meta-analyses indicated intervention with an isocaloric diet plus supplement was more effective in reducing C-reactive protein (CRP) [standard mean difference (SMD): 0.44; 95% CI: 0.20, 0.68; P = 0.0003] and tumor necrosis factor-alpha (TNF-α) (SMD: 0.74; 95% CI: 0.02, 1.46; P = 0.03) than an isocaloric diet alone. No significant weighting was shown between a hypocaloric diet with or without supplementation for CRP (SMD: 0.30; 95% CI: -0.84, 1.44; P = 0.60) and TNF-α (SMD: 0.01; 95% CI: -0.43, 0.45; P = 0.97). In conclusion, hypocaloric and energy-restricted diets alone or with supplementation, and isocaloric diets with supplementation were shown to be most effective in improving the inflammatory profile of patients with NAFLD. To better determine the effectiveness of dietary intervention alone on a NAFLD population, further investigations of longer durations, with larger sample sizes are required.
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The effects of dietary patterns and food groups on symptomatic osteoarthritis: A systematic review.
Zeng, J, Franklin, DK, Das, A, Hirani, V
Nutrition & dietetics: the journal of the Dietitians Association of Australia. 2023;80(1):21-43
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Osteoarthritis is a chronic joint disease that can lead to disability, characterised by the deterioration and loss of joint cartilage, inflammation, pain, aches, and stiffness. Research has shown a positive association between osteoarthritis progression and pro-inflammatory diets, such as Western diets, and a negative association with anti-inflammatory diets, such as the DASH and Mediterranean diets. This systematic review evaluated the evidence from the literature to show the positive and negative associations between osteoarthritis and diet. The Prudent diet, Mediterranean diet, and increased fibre intake were effective in reducing the progression of osteoarthritis and alleviating its symptoms, while the Western diet increased the progression of symptomatic osteoarthritis. The Prudent diet was found to be particularly effective in alleviating symptomatic osteoarthritis. The beneficial effects of anti-inflammatory diets and increased fibre intake are thought to be due to the reduction and suppression of inflammatory cytokines, while inflammatory diets have the opposite effect. Although there is high heterogeneity between the studies, healthcare professionals can use the results of this systematic review to understand the therapeutic clinical utility of anti-inflammatory diets and high-fibre intake in reducing the progression of symptomatic osteoarthritis in people above the age of 45 years. Further robust studies are needed to evaluate the effectiveness of other therapeutic dietary strategies.
Abstract
AIM: To systematically review current literature to determine the association between symptomatic osteoarthritis and dietary patterns, diet quality and food groups in adults aged ≥45 years. METHODS The review was registered on PROSPERO (CRD42021270891). Cochrane Central Library, Cumulative Index of Nursing and Allied Health Literature, Embase, Medline and Web of Science databases were searched. A total of 3816 records were identified. Eligible articles involved populations aged ≥45 years with symptomatic osteoarthritis, assessing dietary patterns, diet quality or food groups, with pain in joints as outcomes. The Joanna Briggs Institute Critical Appraisal Checklists were used for quality assessment. Grading of Recommendations, Assessment, Development and Evaluation was used to assess the certainty of evidence. RESULTS Six cohort studies were included. The Prudent dietary pattern and the Mediterranean dietary pattern reduced the progression of osteoarthritis symptoms. The Western dietary pattern increased symptomatic osteoarthritis progression. Increased total fibre consumption reduced symptomatic osteoarthritis progression and pain worsening, but the effects of fibre from each food group were inconclusive. Diet with high inflammatory potential increased risk of new onset symptomatic osteoarthritis, but the effects of overall diet quality were inconclusive. CONCLUSIONS The Prudent dietary pattern showed the highest protection on symptomatic osteoarthritis in adults aged 45 years and over. The body of evidence is limited, suggesting that further research is needed to corroborate the estimated effect at a high certainty of evidence, and to incorporate previously unstudied dietary patterns and food groups. Identifying the most beneficial dietary pattern may inform future guidelines for reducing symptomatic osteoarthritis in middle aged and older adults.
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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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Interaction of cervical microbiome with epigenome of epithelial cells: Significance of inflammation to primary healthcare.
Holubekova, V, Kolkova, Z, Kasubova, I, Samec, M, Mazurakova, A, Koklesova, L, Kubatka, P, Rokos, T, Kozubik, E, Biringer, K, et al
Biomolecular concepts. 2022;13(1):61-80
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A female health is one medical area of the framework strategies in predictive, preventive, and personalized (3P) medicine. Cervical cancer is preventable and successfully treatable at early stages that makes the disease as an ideal candidate applicable in the context of 3P medicine. The aim of this study was to examine the interaction of the cervical microbiome with epithelial cells in relation to inflammation, and to assess direct evidence of epigenetic changes related to the cervical microbiome. This study is a systematic review of publications in the field of cervical cancer research. This review shows that: - cervical cancer screening in future integration of precision cancer prevention regimes should match an individual’s risk of cancer in context with genomic and environmental factors. - identification of microbiome population might be one of the key aspects of precision medicine in the future. Microbial composition may early identify the potential risk of precancerous lesion formation or permanent bacterial vaginosis. - the composition of the microbiome can be influenced by dietary composition, which will also affect the epigenetic background of the microbiome. However, food forms the microbiome through epigenetic mechanisms, and it is thus necessary to clarify how cancer risk is increased due to food-related microbially produced metabolites. - an examination of the metabolites during inflammation of the cervical epithelium and bacterial vaginosis may improve the precise identification of inflammatory-induced biomarkers that could aid in the precision medicine in prediction of the risk of cervical dysplasia development. - cancer-associated inflammation pathways can be influenced by phytochemicals with anti-inflammatory effects on immune cells, suppression of proinflammatory transcription factors, cytokines, and chemokines. The biological balance between uncontrolled chronic inflammation and controlled inflammation is essential for cancer prevention, prediction, and prognostication. Authors conclude that their review highlighted the pivotal contribution of cervical microbiome, epigenetic changes, and inflammation to the formation of cervical intraepithelial lesion and progression to cervical cancer.
Abstract
One pillar of the predictive, preventive, and personalized medicine framework strategies is the female health. The evaluation of women's lifestyle and dietary habits in context with genetic and modifiable risk factors may reflect the prevention of cervical cancer before the occurrence of clinical symptoms and prediction of cervical lesion behavior. The main aim of this review is to analyze publications in the field of precision medicine that allow the use of research knowledge of cervical microbiome, epigenetic modifications, and inflammation in potential application in clinical practice. Personalized approach in evaluating patient's risk of future development of cervical abnormality should consider the biomarkers of the local microenvironment characterized by the microbial composition, epigenetic pattern of cervical epithelium, and presence of chronic inflammation. Novel sequencing techniques enable a more detailed characterization of actual state in cervical epithelium. Better understanding of all changes in multiomics level enables a better assessment of disease prognosis and selects the eligible targeted therapy in personalized medicine. Restoring of healthy vaginal microflora and reversing the outbreak of cervical abnormality can be also achieved by dietary habits as well as uptake of prebiotics, probiotics, synbiotics, microbial transplantation, and others.
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Nutritional intervention for diabetes mellitus with Alzheimer's disease.
Li, Z, Li, S, Xiao, Y, Zhong, T, Yu, X, Wang, L
Frontiers in nutrition. 2022;9:1046726
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Diabetes Mellitus (DM) affects more than 463 million people worldwide. Similarly, the number of deaths related to Alzheimer’s disease (AD) has increased by 145%. There are several common risk factors for Type 2 Diabetes and AD, including obesity, insulin resistance, and ageing, as well as common pathological mechanisms, including altered insulin signalling, oxidative stress, neuroinflammation, mitochondrial dysfunction, formation of glycated proteins and metabolic syndrome. This review aims to summarize the therapeutic effects of different nutritional therapy strategies on the reduction of DM and AD risk. Controlling blood sugar levels and reducing calorie intake is crucial to preventing diabetes and Alzheimer's disease. The low-carbohydrate, ketogenic, and Mediterranean diets have been found to improve glucose control in people with Type 2 diabetes (T2D). In addition, MIND (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay) and a ketogenic diet may improve cognition in AD patients. Lactobacillus, Bifidobacterium probiotics, and prebiotics, such as inulin, may inhibit the progression of T2D and AD diseases by suppressing inflammation and modulating gut microbes. In addition, vitamins A, C, D, E, B6, B12, folate, long-chain polyunsaturated fatty acids, zinc, magnesium, and polyphenols may improve cognitive decline, homocysteine levels, and insulin resistance in AD and T2D patients. Healthcare professionals can use the results of this review to understand the beneficial effects of dietary strategies and multi-nutrient supplementation on DM and AD. However, further robust studies are required to investigate the risk factors and underlying mechanisms behind DM-combined AD progression.
Abstract
The combined disease burden of diabetes mellitus (DM) and Alzheimer's disease (AD) is increasing, and the two diseases share some common pathological changes. However, the pharmacotherapeutic approach to this clinical complexity is limited to symptomatic rather than disease-arresting, with the possible exception of metformin. Whether nutritional intervention might extend or synergize with these effects of metformin is of interest. In particular, dietary patterns with an emphasis on dietary diversity shown to affect cognitive function are of growing interest in a range of food cultural settings. This paper presents the association between diabetes and AD. In addition, the cross-cultural nutritional intervention programs with the potential to mitigate both insulin resistance (IR) and hyperglycemia, together with cognitive impairment are also reviewed. Both dietary patterns and nutritional supplementation showed the effects of improving glycemic control and reducing cognitive decline in diabetes associated with AD, but the intervention specificity remained controversial. Multi-nutrient supplements combined with diverse diets may have preventive and therapeutic potential for DM combined with AD, at least as related to the B vitamin group and folate-dependent homocysteine (Hcy). The nutritional intervention has promise in the prevention and management of DM and AD comorbidities, and more clinical studies would be of nutritional scientific merit.
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Exploring the Therapeutic Potential of Phytochemicals in Alzheimer's Disease: Focus on Polyphenols and Monoterpenes.
Piccialli, I, Tedeschi, V, Caputo, L, D'Errico, S, Ciccone, R, De Feo, V, Secondo, A, Pannaccione, A
Frontiers in pharmacology. 2022;13:876614
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Alzheimer’s disease (AD) is a complex chronic neurodegenerative disorder characterized by the irreversible loss of memory and brain functions. Many different hypotheses are circulating to explain the underlying cause of the disease, yet therapeutic strategies to treat the degenerative processes have been unsuccessful to date. In recent years research has broadened its focus, viewing the pathology of AD more as an interplay of many factors whilst also taking into account other comorbidities associated with AD, such as insulin resistance and low energy production in the brain. One of the big challenges for clinical treatment is that by the time symptoms present and the diagnosis is made, irreversible brain loss has already occurred. Many lifestyle interventions can influence the modifiable risk factors of ageing and hence present a promising preventative strategy for AD. Plant-derived compounds found in foods and medicinal herbs have received much interest due to their versatile action potential. This review specifically looked at compounds in the polyphenols and monoterpenes category and summarized the current evidence, possible mechanisms of action and how this could aid AD management. An overview of the various hypothesis believed to contribute to the development of AD is presented. These include Aβ aggregation and toxicity, Tau hyperphosphorylation and toxicity, oxidative stress and mitochondrial dysfunction, neuroinflammation and brain insulin resistance. A synopsis of the current state of treatments and treatment development is provided, before exploring the potential of plant-derived compounds, in particular polyphenols and monoterpenes and their potential from various sources. Concluding remarks discuss the challenges that come with turning plant-derived compounds into drug treatments. Many studies on mechanisms of action show therapeutic potential, clinical trials in humans have not yet managed to mirror those effects sufficiently. There is a need to advance the field further and assess more thoroughly the clinical relevance of these findings. This review yields a comprehensive and detailed summary of aspects of AD, the proposed mechanisms and the potential of some nutrition related management options.
Abstract
Alzheimer's disease (AD) is a chronic, complex neurodegenerative disorder mainly characterized by the irreversible loss of memory and cognitive functions. Different hypotheses have been proposed thus far to explain the etiology of this devastating disorder, including those centered on the Amyloid-β (Aβ) peptide aggregation, Tau hyperphosphorylation, neuroinflammation and oxidative stress. Nonetheless, the therapeutic strategies conceived thus far to treat AD neurodegeneration have proven unsuccessful, probably due to the use of single-target drugs unable to arrest the progressive deterioration of brain functions. For this reason, the theoretical description of the AD etiology has recently switched from over-emphasizing a single deleterious process to considering AD neurodegeneration as the result of different pathogenic mechanisms and their interplay. Moreover, much relevance has recently been conferred to several comorbidities inducing insulin resistance and brain energy hypometabolism, including diabetes and obesity. As consequence, much interest is currently accorded in AD treatment to a multi-target approach interfering with different pathways at the same time, and to life-style interventions aimed at preventing the modifiable risk-factors strictly associated with aging. In this context, phytochemical compounds are emerging as an enormous source to draw on in the search for multi-target agents completing or assisting the traditional pharmacological medicine. Intriguingly, many plant-derived compounds have proven their efficacy in counteracting several pathogenic processes such as the Aβ aggregation, neuroinflammation, oxidative stress and insulin resistance. Many strategies have also been conceived to overcome the limitations of some promising phytochemicals related to their poor pharmacokinetic profiles, including nanotechnology and synthetic routes. Considering the emerging therapeutic potential of natural medicine, the aim of the present review is therefore to highlight the most promising phytochemical compounds belonging to two major classes, polyphenols and monoterpenes, and to report the main findings about their mechanisms of action relating to the AD pathogenesis.
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Sedentary behavior and cancer-an umbrella review and meta-analysis.
Hermelink, R, Leitzmann, MF, Markozannes, G, Tsilidis, K, Pukrop, T, Berger, F, Baurecht, H, Jochem, C
European journal of epidemiology. 2022;37(5):447-460
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Globally, cancer is one of the leading causes of death. In modern day-to-day life, sedentary behaviour is prevalent, with adults spending an average of 8.2 hours without any physical activity. It is believed that sedentary behaviour plays a significant role in the increase in all-cause mortality, obesity, chronic diseases, and cancer risk. The purpose of this review and meta-analysis was to examine previous studies that reported associations between sedentary behaviour and cancer incidence and all-cancer mortality. A total of 14 meta-analyses were included in the study, and the strength of the evidence for each association was rated. A significant association was found between sedentary behaviour and cancer incidence across various cancer sites, including ovarian, endometrial, colon, breast, rectal, and prostate cancers. All-cancer mortality also showed positively significant associations with sedentary behaviour. There is a need for further research to evaluate the mechanisms associated with sedentary behaviour and the development of cancer at various sites. However, the results of this study can be used by healthcare professionals to better understand the importance of recommending physical activity and other therapeutic strategies.
Abstract
Several systematic reviews and meta-analyses have summarized the association between sedentary behavior (SB) and cancer. However, the level of evidence and the potential for risk of bias remains unclear. This umbrella review summarized the current data on SB in relation to cancer incidence and mortality, with a particular emphasis on assessing the risk of bias. We searched PubMed, Web of Science and Cochrane Database for systematic reviews and meta-analyses on the association between SB and cancer incidence and mortality. We also searched for recent observational studies not yet included in existing meta-analyses. We re-calculated summary risk estimates for cancer incidence and mortality using random effects models. We included 14 meta-analyses covering 17 different cancer sites from 77 original studies. We found that high SB levels increase the risk for developing ovarian, endometrial, colon, breast, prostate, and rectal cancers, with relative risks of 1.29 (95% confidence interval (CI) = 1.08-1.56), 1.29 (95% CI = 1.16-1.45), 1.25 (95% CI = 1.16-1.33), 1.08 (95% CI = 1.04-1.11), 1.08 (95% CI = 1.00-1.17), and 1.07 (95% CI = 1.01-1.12), respectively. Also, we found an increased risk of cancer mortality of 1.18 (95% CI = 1.09-1.26). Most associations between SB and specific cancer sites were supported by a "suggestive" level of evidence. High levels of SB are associated with increased risk of several types of cancer and increased cancer mortality risk.