Does curcumin improve liver enzymes levels in nonalcoholic fatty liver disease? A systematic review, meta-analysis, and meta-regression.

The aim of this meta-analysis is to investigate the sources of heterogeneity in randomized clinical trials examining the effects of curcumin supplementation on liver aminotransferases in subjects with nonalcoholic fatty liver disease (NAFLD). We conducted a systematic search of the PubMed, SCOPUS, and Web of Science databases for randomized clinical trials and identified 15 studies (n = 835 subjects). We used random-effects models with DerSimonian-Laird methods to analyze the serum levels of alanine aminotransferase and aspartate aminotransferase enzymes. Our results indicate that curcumin did not affect serum alanine aminotransferase, but it did reduce aspartate aminotransferase levels. Notably, both outcomes showed high heterogeneity (p < 0.01). Subgroup analysis revealed that adding piperine to curcumin did not benefit aminotransferase levels in NAFLD patients. Additionally, we found a negative correlation between the duration of the intervention and the relative (mg/kg/day) curcumin dose with the reduction in liver aminotransferases. In summary, the sources of heterogeneity identified in our study are likely attributed to the duration of the intervention and the relative dose of curcumin. Consequently, longer trials utilizing high doses of curcumin could diminish the positive impact of curcumin in reducing serum levels of aminotransferases in patients with NAFLD.

The role of muscle disuse in muscular and cardiovascular fitness: A systematic review and meta-regression.

We aimed to assess the effects of muscle disuse on muscle strength (MS), muscle mass (MM) and cardiovascular fitness. Databases were scrutinized to identify human studies assessing the effects of muscle disuse on both (1) MM and (2) maximal oxygen uptake (VO2max) and/or MS. Random-effects meta-analysis and meta-regression with initial physical fitness and length of the protocol as a priori determined moderators were performed. We quantitatively analyzed 51 different studies, and the level of significance was set at p < 0.05. Data from the participants in 14 studies showed a decline in both VO2max (SMD: -0.93; 95% CI: -1.27 to -0.58) and MM (SMD: -0.34; 95% CI: -0.57 to -0.10). Data from 47 studies showed a decline in strength (-0.88; 95% CI: -1.04 to -0.73) and mass (SMD: -0.47; 95% CI: -0.58 to -0.36). MS loss was twice as high as MM loss, but differences existed between anatomical regions. Notably, meta-regression analysis revealed that initial MS was inversely associated with MS decline. VO2max and MS decline to a higher extent than MM during muscle disuse. We reported a more profound strength loss in subjects with high muscular strength. This is physiologically relevant for athletes because their required muscular strength can profoundly decline during a period of muscle disuse. It should however be noted that a period of muscle disuse can have devastating consequences in old subjects with low muscular strength.

Early heart and skeletal muscle mitochondrial response to a moderate hypobaric hypoxia environment.

In eukaryotic cells, aerobic energy is produced by mitochondria through oxygen uptake. However, little is known about the early mitochondrial responses to moderate hypobaric hypoxia (MHH) in highly metabolic active tissues. Here, we describe the mitochondrial responses to acute MHH in the heart and skeletal muscle. Rats were randomly allocated into a normoxia control group (n = 10) and a hypoxia group (n = 30), divided into three groups (0, 6, and 24 h post-MHH). The normoxia situation was recapitulated at the University of Granada, at 662 m above sea level. The MHH situation was performed at the High-Performance Altitude Training Centre of Sierra Nevada located in Granada at 2320 m above sea level. We found a significant increase in mitochondrial supercomplex assembly in the heart as soon as the animals reached 2320 m above sea level and their levels are maintained 24 h post-exposure, but not in skeletal muscle. Furthermore, in skeletal muscle, at 0 and 6 h, there was increased dynamin-related protein 1 (Drp1) expression and a significant reduction in Mitofusin 2. In conclusion, mitochondria from the muscle and heart respond differently to MHH: mitochondrial supercomplexes increase in the heart, whereas, in skeletal muscle, the mitochondrial pro-fission response is trigged. Considering that skeletal muscle was not actively involved in the ascent when the heart was beating faster to compensate for the hypobaric, hypoxic conditions, we speculate that the different responses to MHH are a result of the different energetic requirements of the tissues upon MHH. KEY POINTS: The heart and the skeletal muscle showed different mitochondrial responses to moderate hypobaric hypoxia. Moderate hypobaric hypoxia increases the assembly of the electron transport chain complexes into supercomplexes in the heart. Skeletal muscle shows an early mitochondrial pro-fission response following exposure to moderate hypobaric hypoxia.

A Comprehensive Review of the Effect of Honey on Human Health.

Honey is a nutritious, healthy, and natural food, to which antioxidant, anti-inflammatory, and antimicrobial properties have been attributed, mainly due to its content of phenolic compounds. The aim of this review is to analyze the available evidence of the effect of honey on humans. Forty-eight clinical trials published between 1985 and 2022 were analyzed, with a total of 3655 subjects. More beneficial effects of honey intake than no or negative effects on different cardiovascular and metabolic risk factors, glucose tolerance, mucositis caused by chemo-radiotherapy, cough in children and wound healing, among others have been observed. Although the number of studies conducted to date is limited and the different investigations are not standardized, beneficial effects of honey intake have been observed, especially when its intake replaces the intake of other sweeteners. In addition, honey could be a safe adjuvant to be administered alongside drugs used for certain diseases.

Sustainable-psycho-nutritional intervention programme for a sustainable diet (the 'NutriSOS' study) and its effects on eating behaviour, diet quality, nutritional status, physical activity, metabolic biomarkers, gut microbiota and water and carbon footprints in Mexican population: study protocol of an mHealth randomised controlled trial.

Mexico is going through an environmental and nutritional crisis related to unsustainable dietary behaviours. Sustainable diets could solve both problems together. This study protocol aims to develop a three-stage, 15-week mHealth randomised controlled trial of a sustainable-psycho-nutritional intervention programme to promote Mexican population adherence to a sustainable diet and to evaluate its effects on health and environmental outcomes. In stage 1, the programme will be designed using the sustainable diets, behaviour change wheel and capability, opportunity, motivation, and behaviour (COM-B) models. A sustainable food guide, recipes, meal plans and a mobile application will be developed. In stage 2, the intervention will be implemented for 7 weeks, and a 7-week follow-up period in a young Mexican adults (18-35 years) sample, randomly divided (1:1 ratio) into a control group (n 50) and an experimental group (n 50), will be divided into two arms at week 8. Outcomes will include health, nutrition, environment, behaviour and nutritional-sustainable knowledge. Additionally, socio-economics and culture will be considered. Thirteen behavioural objectives will be included using successive approaches in online workshops twice a week. The population will be monitored using the mobile application consisting of behavioural change techniques. In stage 3, the effects of the intervention will be assessed using mixed-effects models on dietary intake and quality, nutritional status, physical activity, metabolic biomarkers (serum glucose and lipid profile), gut microbiota composition and dietary water and carbon footprints of the evaluated population. Improvements in health outcomes and a decrease in dietary water and carbon footprints are expected.

Added Sugar Consumption in Spanish Children (7-12 y) and Nutrient Density of Foods Contributing to Such Consumption: An Observational Study.

BACKGROUND: Diets rich in free sugars are associated with an increased risk of obesity. The aim of the present study is to estimate the intake of added sugars in the population of Spanish children and analyze the quality of the foods that contribute to this intake. METHODS: An observational study was conducted to collect self-reported information on weekly food consumption in 1775 Spanish children (7-12 years). Nutrient contents were obtained from different databases. Two nutritional density indices were constructed taking into account all nutrients provided and compared with two previously described indices. RESULTS: The average consumption of added sugars in Spanish children was 55.7 ± 1.0 g/day. The products that most contributed to added sugar intake were biscuits (13.3%), cocoa powder (11.1%), sweetened yogurts (9.9%), and dairy desserts (8.6%). Among these, dairy products had considerable nutritional value. Parents' perception of nutritional value was not aligned with the actual nutritional value. CONCLUSION: The consumption of added sugars was higher than recommended. Public awareness efforts should focus on: (1) the reduction of consumption of low-nutritional quality products containing high amounts of added sugars; (2) the industrial reformulation of most consumed products to reduce sugar content and increase valuable nutrients; and (3) nutritional education.

Mitochondrial adaptations to calorie restriction and bariatric surgery in human skeletal muscle: a systematic review with meta-analysis.

OBJECTIVE: We performed a meta-analysis to determine the changes induced by calorie restriction (CR) and bariatric surgery on human skeletal muscle mitochondria. METHODS: A systematic search of Medline and Web of Science was conducted. Controlled trials exploring CR (≥14 days) and mitochondrial function and/or content assessment were included. Moreover, studies analyzing weight loss following gastric surgery were included for comparison purposes. Human muscle data from 28 studies assessing CR (520 muscle samples) and from 10 studies assessing bariatric surgery (155 muscle samples) were analyzed in a random effect meta-analysis with three a priori chosen covariates. MAIN RESULTS: We report a decrease (p < 0.05) (mean (95 % CI)) in maximal mitochondrial state 3 respiration in response to CR (-0.44 (-0.85, -0.03)) but not in response to surgery (-0.33 (-1.18, 0.52)). No changes in mitochondrial content were reported after CR (-0.05 (-0.12, 0.13)) or in response to surgery (0.23 (-0.05, 0.52)). Moreover, data from CR subjects showed a reduction in complex IV (CIV) activity (-0.29 (-0.56, -0.03)) but not in CIV content (-0.21 (-0.63, 0.22)). Similar results were obtained when the length of the protocol, the initial body mass index, and the estimated energy deficit were included in the model as covariates. CONCLUSION: The observation of reduced maximal mitochondrial state 3, uncoupled respiration, and CIV activity without altering mitochondrial content suggests that, in human skeletal muscle, CR mainly modulates intrinsic mitochondrial function.

Does Hypoxia and Stress Erythropoiesis Compromise Cardiac Function in Healthy Adults? A Randomized Trial.

OBJECTIVES: To investigate whether recombinant human erythropoietin (rHuEPO) injections during an altitude training camp impact heart function. METHODS: Thirty (12 women) moderately trained subjects stayed at 2320 m altitude for 4 weeks while training. Subjects were randomized to placebo (isotonic saline) or rHuEPO (20 IU/kg body weight) i.v. injections. Transthoracic echocardiography imaging was acquired 3 days after arrival to altitude and prior to the first placebo or rHuEPO injection as well as one day after the last rHuEPO injection three weeks later. RESULTS: rHuEPO did not alter cardiovascular morphology parameters, systolic or diastolic function. In the placebo group, altitude exposure improved left ventricle (LV) systolic function due to an increased twist angle but rHuEPO had no additional effects. Pulmonary arterial systolic pressure was unaffected in either group. Notably, rHuEPO hampered LV untwist rate without affecting LV early filling. CONCLUSION: rHuEPO provided during mild altitude exposure does not cause any major effects on heart function. The observed alteration in LV untwist induced by rHuEPO is unlikely to have a meaningful clinical effect. Trial Registration Registered on www. CLINICALTRIALS: gov (NCT04227665).

Physiological Benefits and Performance of Sea Water Ingestion for Athletes in Endurance Events: A Systematic Review.

In different endurance events, athletes have limited access to fluid intake, such as ultra-endurance running. For this reason, it is necessary to establish an adequate hydration strategy for this type of long-duration sporting event. Indeed, it seems that the intake of seawater is a suitable hydration alternative to improve post-exercise recovery in this type of endurance event. This seawater is characterized by being a deep natural mineral water of moderate mineralization, which is usually extracted from a depth of about 700 m. Therefore, the aim of this systematic review is to evaluate the efficacy of seawater consumption in both performance and post-exercise recovery in long-duration sport events. A systematic and comprehensive literature search was performed in PubMed, Scopus, and Web of Science in September 2022. Initially, 8 out of 558 articles met the inclusion criteria. Among these eight studies, six were randomized clinical trials, and two were observational studies (one cross-sectional and one prospective study in well-conditioned student athletes). The results showed that deep sea water consumption accelerated the recovery of aerobic capacity and leg muscle capacity on running performance. In addition, the lactate production after the running exercise in seawater was significantly lower than in pure water. In conclusion, the present review demonstrates that seawater consumption could significantly improve the capacity of recovery after exercise.

Seawater Hydration Modulates IL-6 and Apelin Production during Triathlon Events: A Crossover Randomized Study.

A triathlon is an endurance event in which athletes need an efficient hydration strategy since hydration is restricted at different stages. However, it seems that seawater intake can be a suitable hydration alternative for this type of endurance event. Therefore, the aim of this study was to evaluate the efficacy of seawater hydration during a triathlon on cytokine production. Fifteen trained male triathletes (age = 38.8 ± 5.62 years old; BMI = 22.58 ± 2.51 kg/m2) randomly performed three triathlons, one of them consuming seawater (Totum SPORT, Laboratories Quinton International, S.L., Valencia, Spain), the other one consuming tap water ad libitum, and the last a physiologic saline solution as placebo. The triathlon consisted of an 800 m swim, a 90 km bike ride, and a 10 km run. Blood samples were taken at rest and after training, where markers of inflammation, hemoglobin, and hematocrit concentration were assessed. While the seawater was not ergogenic, it significantly increased the release of IL-6 and apelin post-exercise. However, no differences were found between the fractalkine, IL-15, EPO, osteonectin, myostatin, oncostatin, irisin, FSTL1, osteocrin, BDNF, and FGF-21 values over those of the placebo group. The present study demonstrates that hydration with seawater stimulates myokine production, which could lead to improved performance recovery after exercise.

Food made us human: Recent genetic variability and its relevance to the current distribution of macronutrients.

Numerous dietary strategies are currently used for the prevention of metabolic diseases and for weight loss. Some of the strategies that are used do not have an appropriate physiological-nutritional basis and do not take into account the genetic changes that have occurred recently. Thus, in certain cases, they can be harmful to human health. This review aims to explain the genetic mutations that have occurred during human evolution from the first hominids to Homo sapiens and to explain how they have influenced the way we feed ourselves. Some mutations favored brain development and others are related to the digestion of nutrients such as lactose and starch. The influence of the domestication of food and the practice of cooking on human nutrition is also explained. In addition, this review intends to justify the current recommendations on the caloric distribution of macronutrients based on the important influence of genetic changes and adaptations that have occurred in our species.

Physiological Doses of Hydroxytyrosol Modulate Gene Expression in Skeletal Muscle of Exercised Rats.

We tested whether physiological doses of hydroxytyrosol (HT) may alter the mRNA transcription of key metabolic genes in exercised skeletal muscle. Two groups of exercise-trained Wistar rats, HTlow and HTmid, were supplemented with 0.31 and 4.61 mg/kg/d of HT, respectively, for 10 weeks. Another two groups of rats were not supplemented with HT; one remained sedentary and the other one was exercised. After the experimental period, the soleus muscle was removed for qRT-PCR and western blot analysis. The consumption of 4.61 mg/kg/d of HT during exercise increased the mRNA expression of important metabolic proteins. Specifically, 4.61 mg/kg/d of HT may upregulate long-chain fatty acid oxidation, lactate, and glucose oxidation as well as mitochondrial Krebs cycle in trained skeletal muscle. However, a 4.61 mg/kg/d of HT may alter protein translation, as in spite of the increment showed by CD36 and GLUT4 at the mRNA level this was not translated to higher protein content.

Corrigendum to "Stay Fit, Stay Young: Mitochondria in Movement: The Role of Exercise in the New Mitochondrial Paradigm".

[This corrects the article DOI: 10.1155/2019/7058350.].

Mitochondrial Functionality in Inflammatory Pathology-Modulatory Role of Physical Activity.

The incidence and severity of metabolic diseases can be reduced by introducing healthy lifestyle habits including moderate exercise. A common observation in age-related metabolic diseases is an increment in systemic inflammation (the so-called inflammaging) where mitochondrial reactive oxygen species (ROS) production may have a key role. Exercise prevents these metabolic pathologies, at least in part, due to its ability to alter immunometabolism, e.g., reducing systemic inflammation and by improving immune cell metabolism. Here, we review how exercise regulates immunometabolism within contracting muscles. In fact, we discuss how circulating and resident macrophages alter their function due to mitochondrial signaling, and we propose how these effects can be triggered within skeletal muscle in response to exercise. Finally, we also describe how exercise-induced mitochondrial adaptations can help to fight against virus infection. Moreover, the fact that moderate exercise increases circulating immune cells must be taken into account by public health agencies, as it may help prevent virus spread. This is of interest in order to face not only acute respiratory-related coronavirus (SARS-CoV) responsible for the COVID-19 pandemic but also for future virus infection challenges.

Hydroxytyrosol modifies skeletal muscle GLUT4/AKT/Rac1 axis in trained rats.

Training induces a number of healthy effects including a rise in skeletal muscle (SKM) glucose uptake. These adaptations are at least in part due to the reactive oxygen species produced within SKM, which is in agreement with the notion that antioxidant supplementation blunts some training-induced adaptations. Here, we tested whether hydroxytyrosol (HT), the main polyphenol of olive oil, would modify the molecular regulators of glucose uptake when HT is supplemented during exercise. Rats were included into sedentary and exercised (EXE) groups. EXE group was further divided into a group consuming a low HT dose (0.31 mg·kg·d; EXElow), a moderate HT dose (4.61 mg·kg·d; EXEmid), and a control group (EXE). EXE raised glucose transporter type 4 (GLUT4) protein content, Ras-related C3 botulinum toxin substrate 1 (Rac1) activity, and protein kinase b (AKT) phosphorylation in SKM. Furthermore, EXElow blunted GLUT4 protein content and AKT phosphorylation while EXEmid showed a downregulation of the GLUT4/AKT/Rac1 axis. Hence, a low-to-moderate dose of HT, when it is supplemented as an isolated compound, might alter the beneficial effect of training on basal AKT phosphorylation and Rac1 activity in rats.

Functional role of respiratory supercomplexes in mice: SCAF1 relevance and segmentation of the Qpool.

Mitochondrial respiratory complexes assemble into supercomplexes (SC). Q-respirasome (III2 + IV) requires the supercomplex assembly factor (SCAF1) protein. The role of this factor in the N-respirasome (I + III2 + IV) and the physiological role of SCs are controversial. Here, we study C57BL/6J mice harboring nonfunctional SCAF1, the full knockout for SCAF1, or the wild-type version of the protein and found that exercise performance is SCAF1 dependent. By combining quantitative data-independent proteomics, 2D Blue native gel electrophoresis, and functional analysis of enriched respirasome fractions, we show that SCAF1 confers structural attachment between III2 and IV within the N-respirasome, increases NADH-dependent respiration, and reduces reactive oxygen species (ROS). Furthermore, the expression of AOX in cells and mice confirms that CI-CIII superassembly segments the CoQ in two pools and modulates CI-NADH oxidative capacity.

The emerging role of skeletal muscle mitochondrial dynamics in exercise and ageing.

Mitochondria are the hub for energy production within living cells. They can undergo morphological changes in response to nutrient availability and cellular stress. Here, we review how exercise chronically and acutely affects mitochondrial dynamics. Moreover, we discuss whether mitochondrial dysfunction observed in elderly subjects is due to the ageing process per se or due to the associated sedentary state. Finally, we study how endurance exercise can improve mitochondrial dynamics in older subjects, thereby improving their overall health and likely limiting muscle waste.

Virgin Olive Oil and Health: Summary of the III International Conference on Virgin Olive Oil and Health Consensus Report, JAEN (Spain) 2018.

The Mediterranean diet is considered as the foremost dietary regimen and its adoption is associated with the prevention of degenerative diseases and an extended longevity. The preeminent features of the Mediterranean diet have been agreed upon and the consumption of olive oil stands out as the most peculiar one. Indeed, the use of olive oil as the nearly exclusive dietary fat is what mostly characterizes the Mediterranean area. Plenty of epidemiological studies have correlated that the consumption of olive oil was associated with better overall health. Indeed, extra virgin olive oil contains (poly)phenolic compounds that are being actively investigated for their purported biological and pharma-nutritional properties. On 18 and 19 May 2018, several experts convened in Jaen (Spain) to discuss the most recent research on the benefits of olive oil and its components. We reported a summary of that meeting (reviewing several topics related to olive oil, not limited to health) and concluded that substantial evidence is accruing to support the widespread opinion that extra virgin olive oil should, indeed, be the fat of choice when it comes to human health and sustainable agronomy.

Acute/Subacute and Sub-Chronic Oral Toxicity of a Hidroxytyrosol-Rich Virgin Olive Oil Extract.

The objective of this study was to determine the acute (one single dose), subacute (14 days), and sub-chronic (90 days) toxicity of an aqueous virgin olive oil (VOO) extract rich in hydroxytyrosol in rats. For acute/subacute toxicity, rats were divided into three groups. The control group received distilled water (n = 9), another experimental group received a single dose of 300 mg/kg (n = 3), and a third group received one dose of 2000 mg/kg (n = 4) during 14 days. The sub-chronic study included 60rats distributed in three groups (n = 20: 10 males and 10 females) receiving daily different three doses of the VOO extract in the drinking water during 90 days: (1) 100 mg/kg, (2) 300 mg/kg, and (3) 1000 mg/kg. In parallel, a fourth additional group (n = 20: 10 males and 10 females) did not receive any extract (control group). Clinical signs, body weight, functional observations of sensory and motor reactivity, hematological and biochemical analyses, and macroscopic and microscopic histopathology were evaluated. No adverse effects were observed after the administration of the different doses of the hydroxytyrosol-rich VOO extract, which suggests that the enrichment of VOO in its phenolic compound is safe, and can be used as functional foods for the treatment of chronic degenerative diseases.

Human muscular mitochondrial fusion in athletes during exercise.

The main objective of this work was to investigate whether mitochondrial fusion occurs in the skeletal muscle of well-trained athletes in response to high-intensity exercise. Well-trained swimmers (n = 9) performed a duration-matched sprint interval training (SIT) and high-intensity high-volume training (HIHVT) session on separate days. Muscle samples from triceps brachii were taken before, immediately after, and 3 h after the training sessions. Transmission electron microscopy (TEM) was applied to assess mitochondrial morphology. Moreover, expression of genes coding for regulators of mitochondrial fusion and fission were assessed by real-time quantitative PCR. In addition, mitofusin (MFN)2 and optic atrophy 1 (OPA1) were quantified by Western blot analysis. TEM analyses showed that mitochondrial morphology remained altered for 3 h after HIHVT, whereas SIT-induced changes were only evident immediately after exercise. Only SIT increased MFN1 and MFN2 mRNA expression, whereas SIT and HIHVT both increased MFN2 protein content 3 h after exercise. Notably, only HIHVT increased OPA1 protein content. Mitochondrial morphologic changes that suggest fusion occurs in well-adapted athletes during exercise. However, HIHVT appears as a more robust inducer of mitochondrial fusion events than SIT. Indeed, SIT induces a rapid and transient change in mitochondrial morphology.-Huertas, J. R., Ruiz-Ojeda, F. J., Plaza-Díaz, J., Nordsborg, N. B., Martín-Albo, J., Rueda-Robles, A., Casuso, R. A. Human muscular mitochondrial fusion in athletes during exercise.