The effect of high-polyphenol Mediterranean diet on visceral adiposity: the DIRECT PLUS randomized controlled trial.
BMC medicine. 2022;20(1):327
Plain language summary
Visceral adipose tissue (VAT) accumulation is one of the main key factors that differentiate between metabolic healthy and unhealthy obese individuals. VAT is closely related to the development of multiple cardiovascular risk factors. The Mediterranean (MED) diet, high in polyphenol content and rich in plant food sources, was shown to have an enhanced effect on VAT reduction in combination with physical activity (PA), regardless of weight loss The aim of this study was to assess the effect of the MED diet, further enriched with polyphenols, and lower in red and processed meat (“green-MED diet”) on visceral adiposity in the 18-month Dietary Intervention Randomized Controlled Trial-Polyphenols, Unprocessed trial. This study is a randomised controlled trial. Participants were randomly assigned to one of three intervention groups (1:1:1 ratio): healthy dietary guidelines, MED diet, or green-MED diet, all included PA recommendations, with a free gym membership and educational sessions promoting moderate-intensity PA. Results show that participants following the green-MED diet achieved more than twice the degree of VAT reduction compared to those following the MED diet, despite similar weight loss. In fact, VAT loss was specifically related to lower red meat intake and increased walnuts, green tea, Wolfa globosa, and dietary fibre (this was reflected by higher plasma polyphenol and serum folate levels). Authors conclude that a green-MED diet enriched with polyphenols and decreased red meat consumption might serve as an improved version of the MED diet for targeted VAT reduction.
BACKGROUND Mediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT). METHODS In the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3-4 cups/day) and Wolffia globosa (duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues. RESULTS Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m2; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: - 2.7%, green-MED: - 3.9%) and waist circumference (MED: - 4.7%, green-MED: - 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: - 4.2%, MED: - 6.0%, green-MED: - 14.1%; p < 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, and Wolffia globosa; lower red meat intake; higher total plasma polyphenols (mainly hippuric acid), and elevated urine urolithin A polyphenol were significantly related to greater VAT loss (p < 0.05, multivariate models). CONCLUSIONS A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression. TRIAL REGISTRATION ClinicalTrials.gov , NCT03020186.
Consumption of 85% cocoa dark chocolate improves mood in association with gut microbial changes in healthy adults: a randomized controlled trial.
The Journal of nutritional biochemistry. 2022;99:108854
Plain language summary
Disturbances in a person’s mood interrupts their personal well-being and the ability to participate in social interactions, leading to physical health problems such as chronic diseases. The role of diet as a mood regulator has received a great deal of interest. Certain dietary components have been shown to reduce anxiety and depression and improve quality of life. The aim of this study was to investigate the effects of dark chocolate intake on mood in everyday life, with special emphasis on the gut-brain axis. This study is a randomized controlled trial. Participants who met the criteria for eligibility were randomly assigned to one of three groups: (1) control group (CON, n=14); 2) 85% cocoa chocolate group (DC85, n=18); and 3) 70% cocoa chocolate group (DC70, n=16). Results show that daily intake of dark chocolate significantly reduced negative affect in the DC85, but not in the DC70. Furthermore, gut microbial diversity was significantly higher in DC85 than the CON. Authors conclude that dark chocolate has prebiotic effects by restructuring the diversity and composition of the gut microbiome, which may in turn improve mood via the gut-brain axis.
Dark chocolate has long been recognized for its mood-altering properties; however, the evidence regarding the emotional effects of daily dark chocolate intake is limited. Therefore, we aimed to investigate the effects of dark chocolate intake on mood in everyday life, with special emphasis on the gut-brain axis. Two different dark chocolates (85% and 70% cocoa content) were tested in this study. In a randomized controlled trial, healthy adults (20-30 y) consumed either 30 g/d of 85% cocoa chocolate (DC85, n=18); 70% cocoa chocolate (DC70, n=16); or no chocolate (control group, CON; n=14); for 3 weeks. Mood states were measured using the Positive and Negative Affect Schedule (PANAS). Daily consumption of dark chocolate significantly reduced negative affect in DC85, but not in DC70. To assess the association between the mood-altering effects of dark chocolate and the gut microbiota, we performed fecal 16S rRNA sequencing analysis for the DC85 and CON groups. Gut microbial diversity was significantly higher in DC85 than CON (P<.05). Blautia obeum levels were significantly elevated and Faecalibacterium prausnitzii levels were reduced in DC85 compared to CON (P<.05). Furthermore, we found that the observed changes in negative affect scores were negatively correlated with diversity and relative abundance of Blautia obeum (P<.05). These findings indicate that dark chocolate exerts prebiotic effects, as evidenced by its ability to restructure the diversity and abundance of intestinal bacteria; thus, it may improve negative emotional states via the gut-brain axis.
The Involvement of Oxidative Stress in Psoriasis: A Systematic Review.
Antioxidants (Basel, Switzerland). 2022;11(2)
Conflicts of interest:
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
B: Systematic reviews including RCTs of limited number
C: Non-randomized trials, observational studies, narrative reviews
D: Case-reports, evidence-based clinical findings
E: Opinion piece, other
This systematic review aimed to summarise evidence relating to the involvement of oxidative stress in the pathogenesis of psoriasis in adults. Psoriasis is one of the most common chronic skin conditions and is frequently associated with other chronic systemic diseases, for example, cardiovascular disease.
In informing their research questions the authors reference the role of oxidative stress and increased free radicals in DNA alteration, cell protein degradation, apoptosis, tissue injury, lipid oxidation, altered T-helper cell response and secretion of interleukin-17 - all essential stages in the pathogenesis of psoriasis.
Methodology followed standard robust systematic review procedures, including Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and methodological quality and the risk of bias assessment.
A total of 1293 potentially eligible articles were identified of which 79 observational studies were included in the final review. From these, the following were presented:
- 53 studies evaluating the association between 45 markers of oxidative stress (in serum, saliva and urine) in patients with psoriasis and the correlations between those markers and severity and duration of disease
- 8 studies evaluating the role in psoriasis of different genetic polymorphisms in enzymes involved in the redox balance
- 15 studies evaluating the influence of certain topical or systemic treatments in psoriasis on the redox balance as evaluated by PASI or Dermatology Life Quality Index (DLQI), and on several parameters of oxidative stress or other biochemical markers
Most papers highlighted a significant alteration of the redox balance, including a significant decrease in antioxidant markers and enzymes and an increase in pro-oxidant molecules.
In terms of the relationship between oxidative stress markers and duration/severity of psoriasis, the results were mixed with some studies reporting correlations while others did not. Even though no significant correlations were observed in relation to disease duration/severity, notable alterations in the redox balance were found.
Contradictory results were also present, with some studies demonstrating a significant increase in the levels of antioxidant molecules in individuals suffering from psoriasis. The authors hypothesize this may be due to a compensatory increase in antioxidant systems to counterbalance the elevated oxidative stress levels.
The authors describe how several gene polymorphisms encoding molecules involved in redox balance, such as glutathione S-transferase and catalase, were more frequently expressed in psoriasis.
The review of the use of anti-psoriasis therapy showed promising results in reduction of oxidative stress levels, however the authors note the findings should be taken with caution. The number of studies and participants were limited, a wide range of treatments were used, and not all papers confirmed the observed results.
Authors main conclusion: Markers of oxidative stress are elevated in psoriasis and are associated with severity and duration of the disease. The crosstalk between oxidative stress and psoriasis is influenced by several genetic polymorphisms in genes encoding enzymes or markers involved in the redox balance. Anti-psoriasis therapies impact on the concentrations of oxidative stress biomarkers. Future research is needed to understand how these findings can be translated into the management of psoriasis.
- Robust systematic review methodology including an exhaustive analysis of a large number of studies and indices of oxidative stress.
- Registered protocol on PROSPERO (ID 306997).
- Authors discuss the involvement of oxidative stress in the development and evolution of psoriasis and its associated comorbidities, in particular cardiometabolic health.
- Assessment of quality of included studies.
- Qualitative synthesis of observational studies.
- Quantitative analysis and meta-analysis not possible due to significant heterogeneity of the measured markers, different assessment techniques used, and the variety of collected samples.
Funding: By the Doctoral School of the University of Medicine and Pharmacy of Craiova.
Conflicts of Interest: None declared
Clinical practice applications:
- It is clear that oxidative stress plays a role in the pathophysiology of psoriasis. Understanding the role and mechanisms by which it aids the initiation and maintenance of psoriasis can aid the therapeutic approach and management.
- The oxidative stress biomarkers discussed may emerge as important tools in the diagnosis of psoriasis, particularly at the subclinical stage. They may also be found to be essential in evaluating the initiation and development as well as aiding in the therapeutic approach and understanding response.
Considerations for future research:
- Investigation of the utility of oxidative stress biomarkers by assessing circulating serum, plasma, skin, and urinary markers and studying polymorphisms in genes involved in the redox balance is needed.
- Assessing how these findings translate into our understanding of the initiation, development, and management of psoriasis as well as how they impact the therapeutic approach and response is important.
- Prospective cohort studies are needed to support the current findings and explore these future research questions.
Psoriasis is a chronic, immune-mediated inflammatory dermatosis characterized by the appearance of erythematous plaques, covered by white scales, occasionally pruritogenic, and distributed mainly on the extensor areas. Oxidative stress is defined as an imbalance or a transient or chronic increase in the levels of free oxygen/nitrogen radicals, either as a result of the exaggerated elevation in their production or the decrease in their ability to be eliminated by antioxidant systems. Although the pathogenesis of psoriasis remains far from elucidated, there are studies that delineate an involvement of oxidative stress in this skin disorder. Thus, a systematic search was computed in PubMed/Medline, Web of Science and SCOPUS and, in total, 1293 potentially eligible articles exploring this research question were detected. Following the removal of duplicates and the exclusion of irrelevant manuscripts based on the screening of their titles and abstracts (n = 995), 298 original articles were selected for full-text review. Finally, after we applied the exclusion and inclusion criteria, 79 original articles were included in this systematic review. Overall, the data analyzed in this systematic review point out that oxidative stress markers are elevated in psoriasis and share an association with the duration and severity of the disease. The concentrations of these biomarkers are impacted on by anti-psoriasis therapy. In addition, the crosstalk between psoriasis and oxidative stress is influenced by several polymorphisms that arise in genes encoding markers or enzymes related to the redox balance. Although the involvement of oxidative stress in psoriasis remains undisputable, future research is needed to explore the utility of assessing circulating serum, plasma, urinary and/or skin biomarkers of oxidative stress and of studying polymorphisms in genes regulating the redox balance, as well as how can these findings be translated into the management of psoriasis, as well in understanding its pathogenesis and evolution.
Mitochondria-targeted antioxidant supplementation does not affect muscle soreness or recovery of maximal voluntary isometric contraction force following muscle-damaging exercise in untrained men: a randomized clinical trial.
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2022;47(7):762-774
Unaccustomed exercise causes muscle damage resulting in loss of muscle function, which may be attributable to exercise-induced increases in skeletal muscle reactive oxygen species. This study examined the effect of mitochondria-targeted antioxidant supplementation on recovery of muscle function following exercise. Thirty-two untrained men received MitoQ (20 mg/day) or a placebo for 14 days before performing 300 maximal eccentric contractions of the knee extensor muscles of 1 leg. Muscle function was assessed using isokinetic dynamometry before, immediately after, and 24, 48, 72, and 168 hours after exercise. Muscle soreness was assessed using a visual analogue scale 24, 48, 72, and 168 hours after exercise. Blood samples were collected before, immediately after, and 2, 24, 48, 72, and 168 hours after exercise and urine samples were collected before and during the 48 hours after exercise. The reduction in maximal voluntary isometric contraction force and peak concentric torque following exercise was unaffected by MitoQ while recovery of peak eccentric torque was delayed in the MitoQ group. Exercise-induced increases in urine F2-isoprostanes were unaffected by MitoQ. MitoQ augmented exercise-induced increases in plasma creatine kinase levels, while plasma IL-6 was similar between groups. Muscle soreness was not affected by MitoQ. These results indicate that MitoQ does not attenuate post-exercise muscle soreness and may delay recovery of muscle function following eccentric exercise. Trial registration number: ACTRN12620001089921. Novelty: Post-exercise recovery of maximal voluntary isometric contraction force and peak concentric torque were unaffected by MitoQ. MitoQ delayed post-exercise recovery of peak eccentric torque. Post-exercise muscle soreness was unaffected by MitoQ.
Personalized Medicine in Mitochondrial Health and Disease: Molecular Basis of Therapeutic Approaches Based on Nutritional Supplements and Their Analogs.
Molecules (Basel, Switzerland). 2022;27(11)
Mitochondrial diseases (MDs) may result from mutations affecting nuclear or mitochondrial genes, encoding mitochondrial proteins, or non-protein-coding mitochondrial RNA. Despite the great variability of affected genes, in the most severe cases, a neuromuscular and neurodegenerative phenotype is observed, and no specific therapy exists for a complete recovery from the disease. The most used treatments are symptomatic and based on the administration of antioxidant cocktails combined with antiepileptic/antipsychotic drugs and supportive therapy for multiorgan involvement. Nevertheless, the real utility of antioxidant cocktail treatments for patients affected by MDs still needs to be scientifically demonstrated. Unfortunately, clinical trials for antioxidant therapies using α-tocopherol, ascorbate, glutathione, riboflavin, niacin, acetyl-carnitine and coenzyme Q have met a limited success. Indeed, it would be expected that the employed antioxidants can only be effective if they are able to target the specific mechanism, i.e., involving the central and peripheral nervous system, responsible for the clinical manifestations of the disease. Noteworthily, very often the phenotypes characterizing MD patients are associated with mutations in proteins whose function does not depend on specific cofactors. Conversely, the administration of the antioxidant cocktails might determine the suppression of endogenous oxidants resulting in deleterious effects on cell viability and/or toxicity for patients. In order to avoid toxicity effects and before administering the antioxidant therapy, it might be useful to ascertain the blood serum levels of antioxidants and cofactors to be administered in MD patients. It would be also worthwhile to check the localization of mutations affecting proteins whose function should depend (less or more directly) on the cofactors to be administered, for estimating the real need and predicting the success of the proposed cofactor/antioxidant-based therapy.
Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review.
Creatine monohydrate (CrM) is one of the most widely used nutritional supplements among active individuals and athletes to improve high-intensity exercise performance and training adaptations. However, research suggests that CrM supplementation may also serve as a therapeutic tool in the management of some chronic and traumatic diseases. Creatine supplementation has been reported to improve high-energy phosphate availability as well as have antioxidative, neuroprotective, anti-lactatic, and calcium-homoeostatic effects. These characteristics may have a direct impact on mitochondrion's survival and health particularly during stressful conditions such as ischemia and injury. This narrative review discusses current scientific evidence for use or supplemental CrM as a therapeutic agent during conditions associated with mitochondrial dysfunction. Based on this analysis, it appears that CrM supplementation may have a role in improving cellular bioenergetics in several mitochondrial dysfunction-related diseases, ischemic conditions, and injury pathology and thereby could provide therapeutic benefit in the management of these conditions. However, larger clinical trials are needed to explore these potential therapeutic applications before definitive conclusions can be drawn.
Sponsored Journal Article
Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial
Covid-19 is a disease of the lungs, which differentially affects those it infects. There are currently no therapies that have been approved for use in Covid-19 patients. However recent evidence has highlighted a possible link between the gut and the lungs, known as the gut-lung axis indicating a new avenue for investigation. Previous trials on probiotics have indicated a role in infections such as cold and flu highlighting a possible role in Covid-19 infection. This randomised control trial of 300 Covid-19 patients aimed to determine the efficacy and safety of a probiotic known as AB21 containing several strains of Lactoplantibacillus plantarum and Pediococcus acidilactici. The results showed that after 30 days, the rate of remission from Covid-19 was higher in those who were given the probiotic, which was regardless of age, sex, confounding metabolic illness, viral load, and days from symptom start. Symptom duration and viral load were also reduced with probiotic use. Higher amounts of Covid-19 associated immune activity and lower biomarkers of inflammation were also reported following probiotic use. Probiotic use was shown to be safe during Covid-19 infection. It was concluded that the use of AB21 in Covid-19 patients was safe and associated with increased viral and symptom resolution compared to placebo, possibly driven by immune alterations via the gut-lung axis. This study could be used by healthcare professionals to seriously consider the use of this probiotic to stimulate immune activity and aid viral and symptom resolution in patients suffering from Covid-19.
The Influence of a blend of Probiotic Lactobacillus and Prebiotic Inulin on the Duration and Severity of Symptoms among Individuals with Covid-19
Gut microbial irregularities can lead to increased gut inflammation and gut membrane damage in people with long covid. Symptoms such as cough and breathlessness are apparent in Covid 19 patients with harmful gut bacterial overgrowth. In Covid patients, antibiotic and dexamethasone treatment also aggravates gut microbial imbalances. Lactobacillus supplementation has been shown to lessen upper respiratory tract infection, increase gut bacterial diversity, improve gut wall integrity, reduce gastrointestinal symptoms and gut inflammation, decrease oxidative stress and improve immunity. This study analysed the efficacy of probiotics and prebiotics combined supplements in reducing the severity and longevity of symptomatic Covid infection. 126 participants with Covid symptoms consumed two capsules a day for a month of a supplement containing 5 species of Lactobacillus and chicory inulin. 32% of participants were in the early phase of infection, and 68% were in the late phase. Both early and late phase participants showed significant improvements in cough, fatigue, and subjective wellbeing after 30 days of intervention. The gut symptoms of 82% of the participants improved after a month of intervention. Inulin and Lactobacillus strains need to be studied further robustly to determine whether they provide additional benefits. Healthcare practitioners can use the results of this study to consider symbiotic interventions for those with Covid symptoms.
Dietary Interventions to Treat Type 2 Diabetes in Adults with a Goal of Remission: An Expert Consensus Statement from the American College of Lifestyle
The objective of this Expert Consensus Statement is to assist clinicians in achieving remission of type 2 diabetes (T2D) in adults using diet as a primary intervention. Expert consensus was achieved for 69 statements pertaining to diet and remission of T2D, dietary specifics and types of diets, adjuvant and alternative interventions, support, monitoring, adherence to therapy, weight loss, and payment and policy. Clinicians can use these statements to improve quality of care, inform policy and protocols, and identify areas of uncertainty.
Sponsored Journal Article
IgG-Based Elimination Diet in Migraine Plus Irritable Bowel Syndrome
OBJECTIVES To evaluate therapeutic potential of the immunoglobulin G (IgG)-based elimination diet among migraine patients with irritable bowel syndrome (IBS). BACKGROUND Food elimination has been suggested as an effective and inexpensive therapeutic strategy in patients with migraine and concomitant IBS in the past studies. METHODS A total of 21 patients (mean [standard deviation] age: 38.0 [11.2] years; 85.7% females) diagnosed with migraine and IBS were included in this double-blind, randomized, controlled, cross-over clinical trial composed of baseline (usual diet), first diet (elimination or provocation diets), and second diet (interchange of elimination or provocations diets) phases and 4 visits. RESULTS IgG antibody tests against 270 food antigens revealed mean (standard deviation) reaction count to be 23.1 (14.1). Compared with baseline levels, elimination diet per se was associated with significant reductions in attack count (4.8 [2.1] vs 2.7 [2.0]; P < .001), maximum attack duration (2.6 [0.6] vs. 1.4 [1.1] days; P < .001), mean attack duration (1.8 [0.5] vs. 1.1 [0.8] days; P < .01), maximum attack severity (visual analog scale 8.5 [1.4] vs. visual analog scale 6.6 [3.3]; P < .001), and number of attacks with acute medication (4.0 [1.5] vs. 1.9 [1.8]; P < .001). There was a significant reduction in pain-bloating severity (1.8 [1.3] vs. 3.2 [0.8]; P < .05), pain-bloating within the last 10 days (3.2 [2.8] vs. 5.5 [3.1]; P < .05), and improvement obtained in quality of life (3.6 [1.4] vs. 2.9 [1.0]; P < .05) by the elimination diet as compared with provocation diet. CONCLUSION Our findings indicate that food elimination based on IgG antibodies in migraine patients who suffer from concomitant IBS may effectively reduce symptoms from both disorders with possible positive impact on the quality of life of the patients as well as potential savings to the health-care system.