Nutrients, Volume 13, Issue 1 (January 2021) – 280 articles

Atherosclerosis is a hallmark of most cardiovascular diseases. The implication of macrophages in this pathology is widely documented, notably for their contribution to lipid accumulation within the arterial wall, associated with oxidative stress and inflammation processes. In order to prevent or limit the atherosclerosis damage, nutritional approaches and medicinal plant-based therapies need to be considered. In Reunion Island, medicinal plant-based beverages are traditionally used for their antioxidant, lipid-lowering and anti-inflammatory properties. The aim of our study was to assess the protective effects of eight medicinal plant decoctions in an in vitro model of RAW 264.7 murine macrophages exposed to pro-atherogenic conditions (oxidized low-density lipoproteins—ox-LDL—E. coli Lipopolysaccharides—LPS). The impact of polyphenol-rich medicinal plant decoctions on cell viability was evaluated by Neutral Red assay. Fluorescent ox-LDL uptake was assessed by flow cytometry and confocal microscopy. Activation of NF-κB was evaluated by quantification of secreted alkaline phosphatase in RAW-Blue™ macrophages. Our results show that medicinal plant decoctions limited the cytotoxicity induced by ox-LDL on macrophages. Flow cytometry analysis in macrophages demonstrated that medicinal plant decoctions from S. cumini and P. mauritianum decreased ox-LDL uptake and accumulation by more than 70%. In addition, medicinal plant decoctions also inhibited NF-κB pathway activation in the presence of pro-inflammatory concentrations of E. coli LPS. Our data suggest that medicinal plant decoctions exert protective effects on ox-LDL-induced cytotoxicity and limited macrophage lipid uptake. Moreover, herbal preparations displayed anti-inflammatory properties on macrophages that can be of interest for limiting the atherosclerotic process. Full article

Non-communicable diseases (NCDs) are the first causes of death worldwide. Reduction in the dietary intake of salt and sugars is important lifestyle advice that is useful for NCD prevention. However, the simple recommendations of reducing salt and sugars by healthcare professionals are often ineffective; innovative strategies are therefore necessary. This review aimed at describing the current knowledge about the strategies to reduce dietary salt and sugar intake, including both strategies for the food industry to reduce the salt or sugar of its products and recommendations for health professionals in a clinical context, such as the replacement with substitutes in foods, the gradual reduction to allow a progressive consumer adaptation towards less intense taste, and the different spatial distribution of tastants within the food matrix with taste intensity enhancement. In addition, the cross-modal interaction between two or more different sensory modalities as an innovative strategy for enhancing sweetness and saltiness perception was described. Finally, the dietary tips for salt and sugar reduction were summarized in order to create a comprehensive guide of dietary advices for healthcare professionals for optimizing the management of patients at increased cardiometabolic risk. Full article

Background: The success of Helicobacter pylori (H. pylori) eradication depends on several host and treatment factors. Serum vitamin D levels may be associated with H. pylori infection and eradication rates. We investigated the association between vitamin D and H. pylori infection and eradication, using a large electronic database based on medical records from a population-based health maintenance organization. Methods: Data regarding adults who underwent H. pylori testing and had vitamin D measurements within one month of H. pylori testing were collected. H. pylori infection was ascertained using urea breath or stool antigen tests. A negative H. pylori test following a positive result implied eradication. Multivariate regression models were constructed to assess associations between H. pylori infection, eradication, and vitamin D. Results: Among 150,483 members who underwent H. pylori testing from 2009 to 2018, 27,077 (18%) had vitamin D measurements. Vitamin D levels were inversely associated with H. pylori infection, p < 0.001. The odds of a positive H. pylori test were 31% higher among patients with vitamin D levels <20 ng/mL, compared with those with levels ≥20 ng/mL (OR 1.31, 99% CI 1.22–1.4, p < 0.001). Purchase of vitamin D supplements was associated with a negative subsequent H. pylori test (p < 0.001). Mean vitamin D levels were moderately higher in those with successful vs. failed H. pylori eradication (19.34 ± 9.55 vs. 18.64 ± 9.61, p < 0.001). Conclusions: Vitamin D levels are associated with H. pylori infection. Increased vitamin D levels are associated with successful H. pylori eradication. Vitamin D may have a role in H. pylori eradication. Full article

Breastfeeding is a gold standard of feeding of newborns and infants. Tandem breastfeeding (TBF) is feeding two children of different ages at the same time. The knowledge about the composition of human milk in prolonged lactation is still scarce. Milk from tandem breastfeeding women and after weaning was examined. Milk samples were collected from 13 TBF mothers. A 24-h milk collection was done. Analyses of fat, protein, carbohydrate and energy content were performed using MIRIS. Sociodemographic characteristics of TBF mothers was done. Higher fat content, energy value and total protein concentration was found in TBFM milk during tandem breastfeeding, than in milk after weaning the older child. The carbohydrate content remained stable. The composition of breastmilk, in terms of macronutrients, changes after weaning, taking into account the nutritional requirements of the younger child. The milk of nursing mothers in tandem did not show diurnal variability in individual components. These findings suggest an adaptive role of human milk to nutrient requirements of newborn and older children. The results may support the promotion of long breastfeeding, including tandem breastfeeding. Full article

Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs). Globally, the leading childhood respiratory pathogens are Streptococcus pneumoniae, respiratory syncytial virus and the influenza virus. There is a growing body of evidence describing the innate immunomodulatory properties of vitamin D during challenge with respiratory pathogens, but recent systematic and unbiased synthesis of data is lacking, and future research directions are unclear. We therefore conducted a systematic PubMed literature search using the terms “vitamin D” and “Streptococcus pneumoniae” or “Respiratory Syncytial Virus” or “Influenza”. A priori inclusion criteria restricted the review to in vitro studies investigating the effect of vitamin D metabolites on human innate immune cells (primary, differentiated or immortalised) in response to stimulation with the specified respiratory pathogens. Eleven studies met our criteria. Despite some heterogeneity across pathogens and innate cell types, vitamin D modulated pathogen recognition receptor (PRRs: Toll-like receptor 2 (TLR2), TLR4, TLR7 and nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)) expression; increased antimicrobial peptide expression (LL-37, human neutrophil peptide (HNP) 1-3 and β-defensin); modulated autophagosome production reducing apoptosis; and modulated production of inflammatory cytokines (Interleukin (IL) -1β, tumour necrosis factor-α (TNF-α), interferon-ɣ (IFN-ɣ), IL-12p70, IFN-β, Regulated on Activation, Normal T cell Expressed (RANTES), IL-10) and chemokines (IL-8 and C-X-C motif chemokine ligand 10 (CXCL10)). Differential modulation of PRRs and IL-1β was reported across immune cell types; however, this may be due to the experimental design. None of the studies specifically focused on immune responses in cells derived from children. In summary, vitamin D promotes a balanced immune response, potentially enhancing pathogen sensing and clearance and restricting pathogen induced inflammatory dysregulation. This is likely to be important in controlling both ALRIs and the immunopathology associated with poorer outcomes and progression to chronic lung diseases. Many unknowns remain and further investigation is required to clarify the nuances in vitamin D mediated immune responses by pathogen and immune cell type and to determine whether these in vitro findings translate into enhanced immunity and reduced ALRI in the paediatric clinical setting. Full article

Cardiovascular diseases (CVDs), which include congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, and many other cardiac disorders, cause about 30% of deaths globally; representing one of the main health problems worldwide. Among CVDs, ischemic heart diseases (IHDs) are one of the major causes of morbidity and mortality in the world. The onset of IHDs is essentially due to an unbalance between the metabolic demands of the myocardium and its supply of oxygen and nutrients, coupled with a low regenerative capacity of the heart, which leads to great cardiomyocyte (CM) loss; promoting heart failure (HF) and myocardial infarction (MI). To date, the first strategy recommended to avoid IHDs is prevention in order to reduce the underlying risk factors. In the management of IHDs, traditional therapeutic options are widely used to improve symptoms, attenuate adverse cardiac remodeling, and reduce early mortality rate. However, there are no available treatments that aim to improve cardiac performance by replacing the irreversible damaged cardiomyocytes (CMs). Currently, heart transplantation is the only treatment being carried out for irreversibly damaged CMs. Hence, the discovery of new therapeutic options seems to be necessary. Interestingly, recent experimental evidence suggests that regenerative stem cell medicine could be a useful therapeutic approach to counteract cardiac damage and promote tissue regeneration. To this end, researchers are tasked with answering one main question: how can myocardial regeneration be stimulated? In this regard, natural compounds from plant extracts seem to play a particularly promising role. The present review will summarize the recent advances in our knowledge of stem cell therapy in the management of CVDs; focusing on the main properties and potential mechanisms of natural compounds in stimulating and activating stem cells for myocardial regeneration. Full article

The most common manifestation of cardiovascular (CV) diseases is the presence of arterial hypertension (AH), which impacts on endothelial dysfunction. CV risk is associated with high values of systolic and diastolic blood pressure and depends on the presence of risk factors, both modifiable and not modifiable, such as overweight, obesity, physical exercise, smoking, age, family history, and gender. The main target organs affected by AH are the heart, brain, vessels, kidneys, and eye retina. AH onset can be counteracted or delayed by adopting a proper diet, characterized by a low saturated fat and sodium intake, a high fruit and vegetable intake, a moderate alcohol consumption, and achieving and maintaining over time the ideal body weight. In this review, we analyzed how a new nutritional approach, named caloric restriction diet (CRD), can provide a significant reduction in blood pressure values and an improvement of the endothelial dysfunction. In fact, CRD is able to counteract aging and delay the onset of CV and neurodegenerative diseases through the reduction of body fat mass, systolic and diastolic values, free radicals production, and oxidative stress. Currently, there are few studies on CRD effects in the long term, and it would be advisable to perform observational studies with longer follow-up. Full article

Polyphenols are a group of phytochemicals with potential health-promoting effects. They are classified as flavonoid (flavonols, flavanols, flavones, flavanones, isoflavones, and anthocyanins) and non-flavonoid molecules (phenolic acids, hydroxycinnamic acids, lignans, stilbenes, and tannins). Although an increasing number of trials have shown a correlation among polyphenol consumption and a reduction in risk factors for chronic diseases, discrepancies in explaining their positive effects have been found in terms of the bioavailability. In fact, polyphenols show a low bioavailability due to several factors: interaction with the food matrix, the metabolic processes mediated by the liver (phase I and II metabolism), intestine and microbiota. On the other hand, the biological activities of phenol compounds may be mediated by their metabolites, which are produced in vivo, and recent studies have confirmed that these molecules may have antioxidant and anti-phlogistic properties. This review discusses the studies performed in vivo, which consider the polyphenol bioavailability and their different food sources. Factors influencing the biological effects of the main classes of polyphenols are also considered. Full article

Globally, increasing rates of obesity are one of the most important health issues. The association between breakfast skipping and body weight is contradictory between cross-sectional and interventional studies. This systematic review and meta-analysis aims to summarize this association based on observational longitudinal studies. We included prospective studies on breakfast skipping and overweight/obesity or weight change in adults. The literature was searched until September 2020 in PubMed and Web of Science. Summary risk ratios (RRs) or β coefficients with a 95% confidence interval (CI), respectively, were estimated in pairwise meta-analyses by applying a random-effects model. In total, nine studies were included in the systematic review and three of them were included in the meta-analyses. The meta-analyses indicated an 11% increased RR for overweight/obesity when breakfast was skipped on ≥3 days per week compared to ≤2 days per week (95% CI: 1.04, 1.19, n = two studies). The meta-analysis on body mass index (BMI) change displayed no difference between breakfast skipping and eating (β = −0.02; 95% CI: −0.05, 0.01; n = two studies). This study provides minimal evidence that breakfast skipping might lead to weight gain and the onset of overweight and obesity. Full article

Although multiple studies have identified skipping breakfast as a risk factor for weight gain, there is limited evidence on the clinical impact of skipping lunch and dinner on weight gain. This retrospective cohort study including 17,573 male and 8860 female university students at a national university in Japan, assessed the association of the frequency of breakfast, lunch, and dinner with the incidence of weight gain (≥10%) and overweight/obesity (body mass index ≥ 25 kg/m²), using annual participant health checkup data. Within the observation period of 3.0 ± 0.9 years, the incidence of ≥10% weight gain was observed in 1896 (10.8%) men and 1518 (17.1%) women, respectively. Skipping dinner was identified as a significant predictor of weight gain in multivariable-adjusted Poisson regression models for both men and women (skipping ≥ occasionally vs. eating every day, adjusted incidence rate ratios, 1.42 (95% confidence interval: 1.02–1.98) and 1.67 (1.33–2.09) in male and female students, respectively), whereas skipping breakfast and lunch were not. Similarly, skipping dinner, not breakfast or lunch, was associated with overweight/obesity (1.74 (1.07–2.84) and 1.68 (1.02–2.78) in men and women, respectively). In conclusion, skipping dinner predicted the incidence of weight gain and overweight/obesity in university students. Full article

Despite decades of efforts to reduce sodium intake, excess dietary sodium remains commonplace, and contributes to increased cardiovascular morbidity and mortality independent of its effects on blood pressure. An increasing amount of research suggests that high-sodium diets lead to reduced nitric oxide-mediated endothelial function, even in the absence of a change in blood pressure. As endothelial dysfunction is an early step in the progression of cardiovascular diseases, the endothelium presents a target for interventions aimed at reducing the impact of excess dietary sodium. In this review, we briefly define endothelial function and present the literature demonstrating that excess dietary sodium results in impaired endothelial function. We then discuss the mechanisms through which sodium impairs the endothelium, including increased reactive oxygen species, decreased intrinsic antioxidant defenses, endothelial cell stiffening, and damage to the endothelial glycocalyx. Finally, we present selected research findings suggesting that aerobic exercise or increased intake of dietary potassium may counteract the deleterious vascular effects of a high-sodium diet. Full article

We explored the dose-response relations of sodium, potassium, magnesium and calcium with cardiovascular disease (CVD) risk in the Framingham Offspring Study, as well as the combined effects of these minerals. Analyses included 2362 30–64 year-old men and women free of CVD at baseline. Cox proportional-hazards models were used estimate adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for mineral intakes and incident CVD. Cox models with restricted cubic spline functions were used to examine dose-response relations, adjusting for confounding by age, sex, body mass index, dietary fiber intake, and time-varying occurrence of hypertension. Lower sodium intake (<2500 vs. ≥3500 mg/d) was not associated with a lower risk of CVD. In contrast, potassium intake ≥3000 (vs. <2500) mg/d was associated with a 25% lower risk (95% CI: 0.59, 0.95), while magnesium intake ≥320 (vs. <240) mg/d led to a 34% lower risk (95% CI: 0.51, 0.87) of CVD. Calcium intake ≥700 (vs. <500) mg/d was associated with a non-statistically significant 19% lower risk. Restricted cubic spline curves showed inverse dose-response relations of potassium and magnesium with CVD risk, but no such associations were observed for sodium or calcium. These results highlight the importance of potassium and magnesium to cardiovascular health. Full article

Access to renal transplantation guarantees a substantial improvement in the clinical condition and quality of life (QoL) for end-stage renal disease (ESRD) patients. In recent years, a greater number of older patients starting renal replacement therapies (RRT) have shown the long-term impact of conservative therapies for advanced CKD and the consequences of the uremic milieu, with a frail clinical condition that impacts not only their survival but also limits their access to transplantation. This process, referred to as “inflammaging,” might be reversible with a tailored approach, such as RRT accompanied by specific nutritional support. In this review, we summarize the evidence demonstrating the presence of several proinflammatory substances in the Western diet (WD) and the positive effect of unprocessed food consumption and increased fruit and vegetable intake, suggesting a new approach to reduce inflammaging with the improvement of ESRD clinical status. We conclude that the Mediterranean diet (MD), because of its modulative effects on microbiota and its anti-inflammaging properties, may be a cornerstone in a more precise nutritional support for patients on the waiting list for kidney transplantation. Full article

The mainstay of therapy for chronic kidney disease is control of blood pressure and proteinuria through the use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) that were introduced more than 20 years ago. Yet, many chronic kidney disease (CKD) patients still progress to end-stage kidney disease—the ultimate in failed prevention. While increased oxidative stress is a major molecular underpinning of CKD progression, no treatment modality specifically targeting oxidative stress has been established clinically. Here, we review the influence of oxidative stress in CKD, and discuss regarding the role of the Nrf2 pathway in kidney disease from studies using genetic and pharmacologic approaches in animal models and clinical trials. We will then focus on the promising therapeutic potential of sulforaphane, an isothiocyanate derived from cruciferous vegetables that has garnered significant attention over the past decade for its potent Nrf2-activating effect, and implications for precision medicine. Full article

Colostrum is the milk produced during the first few days after birth and contains high levels of immunoglobulins, antimicrobial peptides, and growth factors. Colostrum is important for supporting the growth, development, and immunologic defence of neonates. Colostrum is naturally packaged in a combination that helps prevent its destruction and maintain bioactivity until it reaches more distal gut regions and enables synergistic responses between protective and reparative agents present within it. Bovine colostrum been used for hundreds of years as a traditional or complementary therapy for a wide variety of ailments and in veterinary practice. Partly due to concerns about the side effects of standard Western medicines, there is interest in the use of natural-based products of which colostrum is a prime example. Numerous preclinical and clinical studies have demonstrated therapeutic benefits of bovine colostrum for a wide range of indications, including maintenance of wellbeing, treatment of medical conditions and for animal husbandry. Articles within this Special Issue of Nutrients cover the effects and use bovine colostrum and in this introductory article, we describe the main constituents, quality control and an overview of the use of bovine colostrum in health and disease. Full article

In an aging society, preventing dysfunction and restoring function of the locomotive organs are necessary for long-term quality of life. Few interventional studies have investigated supplementation for locomotive syndrome. Additionally, very few interventional clinical studies on locomotive syndrome have been performed as placebo-controlled, randomized, double-blind studies. We previously found that the administration of 30% ethanolic extract of Cistanche tubulosa improved walking ability in a cast-immobilized skeletal muscle atrophy mouse model. Therefore, we conducted a clinical study to evaluate the effects of C. tubulosa (CT) extract on the locomotive syndrome. Twenty-six subjects with pre-symptomatic or mild locomotive syndrome completed all tests and were analyzed in the study. Analyses of muscle mass and physical activity were performed based on the full analysis set. Intake of CT extract for 12 weeks increased step width (two-step test) and gait speed (5 m walking test) in patients over 60 years old compared with those in a placebo control (p = 0.046). In contrast, the skeletal muscle mass of the body trunk and limbs was unchanged following administration of CT extract. Adverse effects were evaluated by blood tests; no obvious adverse events were observed following the intake of CT extract. In conclusion, this placebo-controlled, randomized, double-blind study demonstrated that treatment with CT extract significantly prevented a decline in walking ability without any notable adverse effects in patients with locomotive syndrome. Full article

NutritionDay (nDay) is a project established by the Medical University of Vienna and the European Society for Clinical Nutrition and Metabolism (ESPEN) to audit the nutritional status of hospitalized patients and nursing home residents. This study aimed to evaluate nDay data describing the prevalence of hospital malnutrition, nutritional risk factors, and elements of the nutritional care process implemented in hospital wards in 25 European countries and to compare the data derived from Poland with the data collected in all the European countries participating in the study. In total, 10,863 patients (European reference group: 10,863 participants including Poland: 498 participants) were involved in the study. The prevalence of malnutrition was identified on the basis of the ESPEN diagnostic criteria established in 2015, while the prevalence of nutritional risk factors was assessed by analyzing the following parameters: body mass index (BMI), score of Malnutrition Screening Tool (MST), recent weight loss, insufficient food intake, decreased appetite, increased number of drugs intake, reduced mobility, and poor self-reported health status. Malnutrition prevalence was 12.9% in patients from the European reference group and 9.4% in patients from Polish hospital wards (p < 0.05). However, the prevalence of some nutritional risk factors, i.e., recent weight loss, history of decreased food intake, and low actual food intake, were approximately four times more prevalent than diagnosed malnutrition (referring to approximately 40–50% of all participants). In comparison to the European reference group, the significant differences observed in Polish hospital wards concerned mainly dietitian’s involvement in the process of treating malnutrition (16% vs. 57.2%; p < 0.001); supply of special diets (8% vs. 16.1%; p < 0.0001); provision of oral nutritional support (ONS) (3.8% vs. 12.2%; p < 0.0001); prescription of enteral/parenteral nutrition therapy to hospitalized patients (8.2% vs. 11.7%; p < 0.001); as well as recording patient weight performed at hospital admission (100% vs. 72.9%; p < 0.0001), weekly (20% vs. 41.4%; p < 0.05), and occasionally (0% vs. 9.2%). These results indicate that the prevalence of malnutrition and malnutrition risk factors in hospitalized patients in Poland was slightly lower than in the European reference group. However, some elements of the nutritional care process in Polish hospitals were found insufficient and demand more attention. Full article

Background. Due to the critical shortage of kidneys for transplantation, the identification of modifiable factors related to graft failure is highly desirable. The role of trimethylamine-N-oxide (TMAO) in graft failure remains undetermined. Here, we investigated the clinical utility of TMAO and its dietary determinants for graft failure prediction in renal transplant recipients (RTRs). Methods. We included 448 RTRs who participated in the TransplantLines Cohort Study. Cox proportional-hazards regression analyses were performed to study the association of plasma TMAO with graft failure. Net Benefit, which is a decision analysis method, was performed to evaluate the clinical utility of TMAO and dietary information in the prediction of graft failure. Results. Among RTRs (age 52.7 ± 13.1 years; 53% males), the baseline median TMAO was 5.6 (3.0–10.2) µmol/L. In multivariable regression analysis, the most important dietary determinants of TMAO were egg intake (Std. β = 0.09 [95%CI, 0.01; 0.18]; p = 0.03), fiber intake (Std. β = −0.14 [95%CI, −0.22, −0.05]; p = 0.002), and fish and seafood intake (Std. β = 0.12 [95%CI, 0.03,0.21]; p = 0.01). After a median follow-up of 5.3 (4.5–6.0) years, graft failure was observed in 58 subjects. TMAO was associated with an increased risk of graft failure, independent of age, sex, the body mass index (BMI), blood pressure, lipids, albuminuria, and the Estimated Glomerular Filtration Rate (eGFR) (Hazard Ratio per 1-SD increase of TMAO, 1.62 (95% confidence interval (CI): 1.22; 2.14, p < 0.001)). A TMAO and dietary enhanced prediction model offered approximately double the Net Benefit compared to a previously reported, validated prediction model for future graft failure, allowing the detection of 21 RTRs per 100 RTRs tested, with no false positives versus 10 RTRs, respectively. Conclusions. A predictive model for graft failure, enriched with TMAO and its dietary determinants, yielded a higher Net Benefit compared with an already validated model. This study suggests that TMAO and its dietary determinants are associated with an increased risk of graft failure and that it is clinically meaningful. Full article

Peroxisome proliferator-activated receptor-γ2 gene Pro12Ala allele polymorphism (PPARG2 Pro12Ala; rs1801282) has been linked to both cancer risk and dietary factors. We conducted the first systematic literature review of studies published before December 2020 using the PubMed database to summarize the current evidence on whether dietary factors for cancer may differ by individuals carrying C (common) and/or G (minor) alleles of the PPARG2 Pro12Ala allele polymorphism. The inclusion criteria were observational studies that investigated the association between food or nutrient consumption and risk of incident cancer stratified by PPARG2 Pro12Ala allele polymorphism. From 3815 identified abstracts, nine articles (18,268 participants and 4780 cancer cases) covering three cancer sites (i.e., colon/rectum, prostate, and breast) were included. CG/GG allele carriers were more impacted by dietary factors than CC allele carriers. High levels of protective factors (e.g., carotenoids and prudent dietary patterns) were associated with a lower cancer risk, and high levels of risk factors (e.g., alcohol and refined grains) were associated with a higher cancer risk. In contrast, both CG/GG and CC allele carriers were similarly impacted by dietary fats, well-known PPAR-γ agonists. These findings highlight the complex relation between PPARG2 Pro12Ala allele polymorphism, dietary factors, and cancer risk, which warrant further investigation. Full article

The increased usage of alternative Ayurvedic treatments as potential health-beneficial therapies emphasizes the importance of studying its efficacy in sound placebo-controlled intervention trials. An example of such a traditional Ayurvedic herbal preparation is Mohana Choorna, a mixture composed of 20 different herbs and used to prevent and treat type 2-diabetes (T2D). We studied the efficacy of “Mohana Choorna” on T2D-related parameters in subjects with impaired glucose tolerance. In a double blind, placebo-controlled cross-over trial, 19 overweight (BMI > 27 kg/m²) subjects aged 50–70 years with an impaired glucose tolerance received two four-week interventions, i.e., herbal or placebo with a four-week wash-out between interventions. HbA1c, glucose, insulin, triglycerides, cholesterol, blood pressure and augmentation index were measured before and after both interventions at fasting and during a glucose tolerance test. After both interventions, urine was collected to measure treatment exposure using LCMS-based metabolomics and whole genome gene-expression in adipose tissue of 13 subjects. The herbal intervention did not affect plasma glucose triglycerides, cholesterol, blood pressure or the augmentation index but showed a trend towards an increased insulin, HOMA-IR and postprandial insulin levels (p = 0.054, p = 0.056 and p = 0.095 respectively). An increase in expression of inflammation-related gene sets in adipose tissue was observed after the herbal intervention compared to placebo. Urine metabolomic analysis did not reveal a correlation of the presence of specific plant metabolites with “health markers”. Our findings suggest that there is no substantiating evidence to claim that four weeks’ use of the Ayurvedic herbal supplement Mohana Choorna beneficially affects glucose homeostasis. Full article

Diets could play an important role in testicular function, but studies on how adherence to the dietary patterns influences human testicular function in Asian countries are scarce. Herein, we examined the association between testosterone-related dietary patterns and testicular function among adult men in Taiwan. This cross-sectional study recruited 3283 men who attended a private medical screening program from 2009 to 2015. Testosterone-related dietary pattern was generated by the reduced rank regression (RRR) method. The association between adherence to quartile of dietary pattern scores with sex hormones (testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2)) and sperm quality (sperm concentration (SC), total sperm motility (TSM), progressive motility (PRM), and normal sperm morphology (NSM)) were examined by multivariable linear regression. Hemoglobin (β = 0.57, p < 0.001), hematocrit (β = 0.17, p = 0.002), triglyceride (β = −0.84, p < 0.001), HDL-cholesterol (β = 3.58, p < 0.001), total cholesterol to HDL-cholesterol ratio (β = −0.78, p < 0.001), and uric acid (β = −10.77, p < 0.001) were highly correlated with testosterone levels. Therefore, these biomarkers were used to construct a testosterone-related dietary pattern. Highest adherence (Q4) to dietary pattern scores were negatively associated with lower testosterone in the pooled analysis (β = −0.89, p = 0.037) and normal-weight men (β = −1.48, p = 0.019). Likewise, men in the Q4 of the dietary pattern had lower SC (β = −5.55, p = 0.001) and NSM (β = −2.22, p = 0.007) regardless of their nutritional status. Our study suggesting that testosterone-related dietary pattern (rich in preserved vegetables or processed meat or fish, deep-fried foods, innards organs, rice or flour products cooked in oil, and dipping sauce, but low in milk, dairy products, legumes, or beans, and dark or leafy vegetables) was associated with a poor testicular function. Full article

Diabetic kidney disease (DKD) is a debilitating complication of diabetes, which develops in 40% of the diabetic population and is responsible for up to 50% of end-stage renal disease (ESRD). Tocotrienols have shown to be a potent antioxidant, anti-inflammatory, and antifibrotic agent in animal and clinical studies. This study evaluated the effects of 400 mg tocotrienol-rich vitamin E supplementation daily on 59 DKD patients over a 12-month period. Patients with stage 3 chronic kidney disease (CKD) or positive urine microalbuminuria (urine to albumin creatinine ratio; UACR > 20–200 mg/mmol) were recruited into a randomized, double-blind, placebo-controlled trial. Patients were randomized into either intervention group (n = 31) which received tocotrienol-rich vitamin E (Tocovid SupraBio^TM; Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules (n = 28) for 12 months. HbA1c, renal parameters (i.e., serum creatinine, eGFR, and UACR), and serum biomarkers were collected at intervals of two months. Tocovid supplementation significantly reduced serum creatinine levels (MD: −4.28 ± 14.92 vs. 9.18 ± 24.96), p = 0.029, and significantly improved eGFR (MD: 1.90 ± 5.76 vs. −3.29 ± 9.24), p = 0.011 after eight months. Subgroup analysis of 37 patients with stage 3 CKD demonstrated persistent renoprotective effects over 12 months; Tocovid improved eGFR (MD: 4.83 ± 6.78 vs. −1.45 ± 9.18), p = 0.022 and serum creatinine (MD: −7.85(20.75) vs. 0.84(26.03), p = 0.042) but not UACR. After six months post washout, there was no improvement in serum creatinine and eGFR. There were no significant changes in the serum biomarkers, TGF-β1 and VEGF-A. Our findings verified the results from the pilot phase study where tocotrienol-rich vitamin E supplementation at two and three months improved kidney function as assessed by serum creatinine and eGFR but not UACR. Full article

There is evidence demonstrating that heart failure (HF) occurs in 1–2% of the global population and is often accompanied by comorbidities which contribute to increasing the prevalence of the disease, the rate of hospitalization and the mortality. Although recent advances in both pharmacological and non-pharmacological approaches have led to a significant improvement in clinical outcomes in patients affected by HF, residual unmet needs remain, mostly related to the occurrence of poorly defined strategies in the early stages of myocardial dysfunction. Nutritional support in patients developing HF and nutraceutical supplementation have recently been shown to possibly contribute to protection of the failing myocardium, although their place in the treatment of HF requires further assessment, in order to find better therapeutic solutions. In this context, the Optimal Nutraceutical Supplementation in Heart Failure (ONUS-HF) working group aimed to assess the optimal nutraceutical approach to HF in the early phases of the disease, in order to counteract selected pathways that are imbalanced in the failing myocardium. In particular, we reviewed several of the most relevant pathophysiological and molecular changes occurring during the early stages of myocardial dysfunction. These include mitochondrial and sarcoplasmic reticulum stress, insufficient nitric oxide (NO) release, impaired cardiac stem cell mobilization and an imbalanced regulation of metalloproteinases. Moreover, we reviewed the potential of the nutraceutical supplementation of several natural products, such as coenzyme Q10 (CoQ10), a grape seed extract, Olea Europea L.-related antioxidants, a sodium–glucose cotransporter (SGLT2) inhibitor-rich apple extract and a bergamot polyphenolic fraction, in addition to their support in cardiomyocyte protection, in HF. Such an approach should contribute to optimising the use of nutraceuticals in HF, and the effect needs to be confirmed by means of more targeted clinical trials exploring the efficacy and safety of these compounds. Full article

The use of probiotic microorganisms in clinical practice has increased in recent years and a significant number of pregnant women are regular consumers of these products. However, probiotics might modulate the immune system, and whether or not this modulation is beneficial for perinatal outcomes is unclear. We performed a systematic review and meta-analysis to evaluate the reporting of perinatal outcomes in randomized controlled trials including women supplemented with probiotic microorganisms during pregnancy. We also analyzed the effects that the administration of probiotic microorganisms exerts on perinatal outcomes. In the review, 46 papers were included and 25 were meta-analyzed. Reporting of perinatal outcomes was highly inconsistent across the studies. Only birth weight, cesarean section, and weeks of gestation were reported in more than 50% of the studies. Random effects meta-analysis results showed that the administration of probiotic microorganisms during pregnancy did not have any a positive or negative impact on the perinatal outcomes evaluated. Subgroup analysis results at the strain level were not significantly different from main analysis results. The administration of probiotic microorganisms does not appear to influence perinatal outcomes. Nonetheless, future probiotic studies conducted in pregnant women should report probiotic strains and perinatal outcomes in order to shed light upon probiotics’ effects on pregnancy outcomes. Full article

Fasting is becoming an increasingly popular practice. Nevertheless, its clinical benefits and possible inconveniences remain limitedly evaluated. We observed the effects of a seven-day fast conducted in a non-medical center located in the Swiss Alps. Clinical parameters were measured on the first and last day of fasting (D1 and D7), and two months later (D60). Among the 40 participants, blood analyses were done on 25 persons with an increased metabolic risk, with the primary goal of assessing the lasting effect on low-density lipoprotein (LDL) cholesterol. By comparing D60 with D1, high-density lipoprotein cholesterol (HDL) (+0.15 mmol/L) and insulin-like growth factor-1 (IGF-1) (+2.05 mmol/L) increased (both p < 0.009), all other blood parameters (LDL, glucose, total cholesterol, triglycerides, C-reactive protein (CRP)) did not change; weight (−0.97 kg) and hearth rate (−7.31 min⁻¹) decreased (both p < 0.006). By comparing D7 with D1, total cholesterol (+0.44 mmol/L), triglycerides (+0.37 mmol/L) and CRP (+3.37 mg/L) increased (all p < 0.02). The lack of LDL variation at D60 may be due to the low metabolic risk level of the participants. The increase of total cholesterol, triglycerides and CRP at D7 warrants studies to understand whether such fluctuations represent a stress reaction to the fasting state, which may vary in different fasting types. Full article

Alzheimer’s disease (AD) is a neurodegenerative disease conceptualized as a clinical-biological neurodegenerative construct where amyloid-beta pathophysiology is supposed to play a role. The loss of cognitive functions is mostly characterized by the rapid hydrolysis of acetylcholine by cholinesterases including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Moreover, both enzymes are responsible for non-catalytic actions such as interacting with amyloid β peptide (Aβ) which further leads to promote senile plaque formation. In searching for a natural cholinesterase inhibitor, the present study focused on two isocoumarines from hydrangea, thunberginol C (TC) and hydrangenol 8-O-glucoside pentaacetate (HGP). Hydrangea-derived compounds were demonstrated to act as dual inhibitors of both AChE and BChE. Furthermore, the compounds exerted selective and non-competitive mode of inhibition via hydrophobic interaction with peripheral anionic site (PAS) of the enzymes. Overall results demonstrated that these natural hydrangea-derived compounds acted as selective dual inhibitors of AChE and BChE, which provides the possibility of potential source of new type of anti-cholinesterases with non-competitive binding property with PAS. Full article

Despite intensive lipid-lowering interventions, patients treated with statins develop atherosclerotic cardiovascular disease (ASCVD), and these patients have an increased risk of developing recurrent cardiovascular events during follow-up. Therefore, there is a need to focus on the residual risks in patients in statin therapy to further reduce ASCVD. The aim of this study was to retrospectively investigate the 10-year trend (2011–2019) regarding changes in polyunsaturated fatty acids (PUFAs) in patients with acute coronary syndrome (ACS) in a single center. We included 686 men and 203 women with ACS admitted to Kagawa Prefectural Central Hospital. Plasma PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-γ-linolenic acid (DGLA), were measured at admission for suspected ACS. A secular decreasing trend in the levels of EPA and DHA and the EPA/AA ratio, but not of AA and DGLA, was observed. The analyses based on age (>70 or <70 years) and sex showed that the decreasing trend in the levels of EPA and DHA did not depend on age and remained significant only in men. Further studies are needed to obtain robust evidence to justify that the administration of n-3 PUFA contributes to the secondary prevention of ACS. Full article

We aimed to assess differences in dietary patterns (i.e., Mediterranean diet and healthy eating indexes) between participants with prediabetes and those with normal glucose tolerance. Secondarily, we analyzed factors related to prediabetes and dietary patterns. This was a cross-sectional study design. From a sample of 594 participants recruited in the Mollerussa study cohort, a total of 535 participants (216 with prediabetes and 319 with normal glucose tolerance) were included. The alternate Mediterranean Diet score (aMED) and the alternate Healthy Eating Index (aHEI) were calculated. Bivariable and multivariable analyses were performed. There was no difference in the mean aMED and aHEI scores between groups (3.2 (1.8) in the normoglycemic group and 3.4 (1.8) in the prediabetes group, p = 0.164 for the aMED and 38.6 (7.3) in the normoglycemic group and 38.7 (6.7) in the prediabetes group, p = 0.877 for the aHEI, respectively). Nevertheless, women had a higher mean of aMED and aHEI scores in the prediabetes group (3.7 (1.9), p = 0.001 and 40.5 (6.9), p < 0.001, respectively); moreover, they had a higher mean of aHEI in the group with normoglycemia (39.8 (6.6); p = 0.001). No differences were observed in daily food intake between both study groups; consistent with this finding, we did not find major differences in nutrient intake between groups. In the multivariable analyses, the aMED and aHEI were not associated with prediabetes (odds ratio (OR): 1.19, 95% confidence interval (CI): 0.75–1.87; p = 0.460 and OR: 1.32, 95% CI: 0.83–2.10; p = 0.246, respectively); however, age (OR: 1.04, 95% CI: 1.02–1.05; p < 0.001), dyslipidemia (OR: 2.02, 95% CI: 1.27–3.22; p = 0.003) and body mass index (BMI) (OR: 1.09, 95% CI: 1.05–1.14; p < 0.001) were positively associated with prediabetes. Physical activity was associated with a lower frequency of prediabetes (OR: 0.48, 95% CI: 0.31–0.72; p = 0.001). In conclusion, subjects with prediabetes did not show a different dietary pattern compared with a normal glucose tolerance group. However, further research is needed on this issue. Full article

Craniofacial development requires extremely fine-tuned developmental coordination of multiple specialized tissues. It has been evidenced that a folate deficiency (vitamin B₉), or its synthetic form, folic acid (FA), in maternal diet could trigger multiple craniofacial malformations as oral clefts, tongue, or mandible abnormalities. In this study, a folic acid-deficient (FAD) diet was administered to eight-week-old C57/BL/6J female mouse for 2–16 weeks. The head symmetry, palate and nasal region were studied in 24 control and 260 experimental fetuses. Our results showed a significant reduction in the mean number of fetuses per litter according to maternal weeks on FAD diet (p < 0.01). Fetuses were affected by cleft palate (3.8%) as well as other severe congenital abnormalities, for the first time related to maternal FAD diet, as head asymmetries (4.6%), high arched palate (3.5%), nasal septum malformed (7.3%), nasopharynx duct shape (15%), and cilia and epithelium abnormalities (11.2% and 5.8%). Dysmorphologies of the nasal region were the most frequent, appearing at just four weeks following a maternal FAD diet. This is the first time that nasal region development is experimentally related to this vitamin deficiency. In conclusion, our report offers novel discoveries about the importance of maternal folate intake on midface craniofacial development of the embryos. Moreover, the longer the deficit lasts, the more serious the consequent effects appear to be. Full article