The effects of cereal ß-glucans on cardiovascular risk factors and the role of the gut microbiome.

The human gut microbiome has emerged as a key influencer of human health and disease, particularly through interactions with dietary fiber. However, national dietary guidelines worldwide are only beginning to capitalize on the potential of microbiome research, which has established the vital role of host-microbe interactions in mediating the physiological effects of diet on overall health and disease. ß-glucans have been demonstrated to modulate the composition of the gut microbiota, leading to improved outcomes in cardiovascular disease (CVD). Raised serum cholesterol and blood pressure are important modifiable risk factors in the development of CVD and emerging evidence highlights the role of the gut microbiota in ameliorating such biomarkers and clinical characteristics of the disease. The proposed mechanism of action of ß-glucans on the pathophysiological mechanisms of disease have yet to be elucidated. Validating gaps in the literature may substantiate ß-glucans as a potential novel dietary therapy against modifiable risk factors for CVD and would further support the public health significance of including a habitual fiber-rich diet.

Mastiha has efficacy in immune-mediated inflammatory diseases through a microRNA-155 Th17 dependent action.

Mastiha is a natural nutritional supplement with known anti-inflammatory properties. Non-alcoholic fatty liver disease (NAFLD) and Inflammatory bowel disease (IBD) are immune mediated inflammatory diseases that share common pathophysiological features. Mastiha has shown beneficial effects in both diseases. MicroRNAs have emerged as key regulators of inflammation and their modulation by phytochemicals have been extensively studied over the last years. Therefore, the aim of this study was to investigate whether a common route exists in the anti-inflammatory activity of Mastiha, specifically through the regulation of miRNA levels. Plasma miR-16, miR-21 and miR-155 were measured by Real-Time PCR before and after two double blinded and placebo-controlled randomized clinical trials with Mastiha. In IBD and particularly in ulcerative colitis patients in relapse, miR-155 increased in the placebo group (p = 0.054) whereas this increase was prevented by Mastiha. The mean changes were different in the two groups even after adjusting for age, sex and BMI (p = 0.024 for IBD and p = 0.042). Although the results were not so prominent in NAFLD, miR-155 displayed a downward trend in the placebo group (p = 0.054) whereas the levels did not changed significantly in the Mastiha group in patients with less advanced fibrosis. Our results propose a regulatory role for Mastiha in circulating levels of miR-155, a critical player in T helper-17 (Th17) differentiation and function.

Development, Validation and Application of a UHPLC-MS Method for the Quantification of Chios Mastic Gum Triterpenoids in Human Plasma.

Chios mastic gum is the resinous secretion obtained from the barks of the shrub Pistacia lentiscus var. Chia, which is endemic to the Greek island of Chios. Since antiquity, Chios mastic gum has found several uses as a phytotherapeutic remedy, primarily for the treatment of gastrointestinal disorders while recently, Chios mastic gum was also recognized by EMA as an herbal medicinal product with specific indications. Chios mastic gum's biological properties are attributed to triterpenes which comprise the major chemical group (approx. 70%) and notably isomasticadienonic acid and masticadienonic acid. However, due to their structural characteristics, the isolation thereof in high yield and purity is challenging and since they are not commercially available, pharmacological studies aiming to assess their biological properties are limited. In the present work, mastic's phytochemical investigation by UPLC-HRMS is followed by the isolation and characterization of isomasticadienonic acid and masticadienonic acid to be used as analytical standards for their accurate and reliable quantification in human plasma. A UHPLC-tQ-MS method that was developed and validated (in terms of specificity, linearity, limit of quantification, accuracy and precision), for the direct quantification of the targeted compounds in the low ng/mL range of concentration, was subsequently implemented on plasma samples of healthy volunteers thus demonstrating its fitness for purpose. The results presented herein might provide insight to the understanding of this traditional natural product consumed notably for its anti-inflammatory, antioxidant and lipid lowering properties. Moreover, this method might serve as a starting point for any study aiming to monitor bioactive triterpenes in biological fluids.

Adherence to Mediterranean diet in Crohn's disease.

PURPOSE: To assess the adherence to MD in patients with Crohn's disease (CD). METHODS: Outpatients with CD were enrolled in this protocol. Medical history, disease activity, dietary intake, habitual Mediterranean diet (MedDiet) score, anthropometric measurements and Inflammatory Bowel Disease Questionnaire (IBDQ) were recorded. Blood samples were collected for quantification of biochemical and inflammatory indices. RESULTS: A total of 86 patients with CD were enrolled: 41 in relapse (5 ≤ Harvey Bradshaw Index ≤ 14) and 45 in remission (Harvey Bradshaw Index ≤ 4). Adherence to MD was greater in patients with inactive disease. The MedDiet score correlated positively with the IBDQ (p = 0.008) and negatively with disease activity (p < 0.001). CONCLUSIONS: Adherence to Mediterranean diet is associated with improved quality of life in CD patients. Higher adherence to Mediterranean diet could be of importance in patients with CD to improve quality of life and reduce disease activity.

The effect of prenatal maternal physical activity and lifestyle in perinatal outcome: results from a Greek study.

BACKGROUND: Several maternal characteristics, including lifestyle, have been associated with perinatal outcomes and birth anthropometric characteristics of the offspring. This study aimed to identify whether physical activity (PA) and other lifestyle parameters of the mother are associated with the pregnancy outcomes or with the infant's birth anthropometric characteristics. METHODS: Participants were recruited in Mitera Maternity Hospital, Athens, Greece. Socio-demographic, medical history and anthropometric assessment took place. PA during pregnancy was assessed with the Pregnancy Physical Activity Questionnaire. Dietary assessment was conducted with the Food Frequency Questionnaire and adherence to the Mediterranean diet was evaluated with the MedDiet score. Birth weight and gestational age data were also collected. RESULTS: Sedentary-intensity activity scores increased with increased educational level, while moderate-intensity activity scores decreased with increased educational level. Pregnant women who delivered large for gestational age infants had lower sports activity score. Higher vigorous and sports activity score was demonstrated in cases with a vaginal delivery compared with caesarean section. PA score was significantly and positively correlated with several nutrient intakes and PA was higher in women with a healthier nutritional pattern. Increased MedDiet scores were found in mothers with increased educational level. CONCLUSIONS: Overall, PA was higher in women with a healthier nutritional pattern. An increased vs. a low activity level during pregnancy is positively associated with vaginal delivery and with the size of the offspring.

Regulation of faecal biomarkers in inflammatory bowel disease patients treated with oral mastiha (Pistacia lentiscus) supplement: A double-blind and placebo-controlled randomised trial.

There is a keen research upon the effects of nutraceuticals on inflammatory bowel disease. The purpose of this study was to explore the effect of mastiha supplement, rich in bioactive nutraceuticals, in active inflammatory bowel disease. This is a randomised, double-blind, placebo-controlled clinical trial. Α total of 60 inflammatory bowel disease patients were enrolled and randomly allocated to mastiha (2.8 g/day) or placebo groups for 3 months adjunct to stable medical treatment. Medical and dietary history, Inflammatory Bowel Disease Questionnaire (IBDQ), Harvey-Bradshaw index, partial Mayo score, biochemical indices, faecal, and blood inflammatory markers were assessed. A clinically important difference between groups in IBDQ was defined as primary outcome. Inflammatory Bowel Disease Questionnaire score significantly improved in verum compared with baseline (p = 0.004). There was a significant decrease in faecal lysozyme in mastiha patients (p = 0.018) with the mean change being significant (p = 0.021), and significant increases of faecal lactoferrin (p = 0.001) and calprotectin (p = 0.029) in the placebo group. Fibrinogen reduced significantly (p = 0.006) with a significant mean change (p = 0.018), whereas iron increased (p = 0.032) in mastiha arm. Our results show regulation of faecal lysozyme by mastiha supplement adjunctive to pharmacological treatments in active inflammatory bowel disease. An effect secondary to a prebiotic potency is proposed.

Healthy Diets to Prevent Obesity and Cardiovascular Diseases in Adolescents.

Since the 1980s, there has been a global increase, decade by decade, in the rates of overweight and obesity among children, both in developed and developing countries [...].

The Role of Dietary Intake in the Weight Loss Outcomes of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy: A Systematic Review and Meta-analysis.

The relationship between postoperative dietary intake and weight loss after bariatric surgery remains unclear. We performed a systematic review and meta-analysis of studies published between January 2000 and May 2023, reporting weight loss outcomes, and dietary intake before and after Roux-en-Y gastric bypass and sleeve gastrectomy. A total of 42 studies were included. There was no detectable difference in dietary intake between the two procedures. Roux-en-Y gastric bypass induced an average decrease in energy intake of 886 kcal/day at 12-month post-surgery; however, there was no correlation between daily energy intake and weight loss. These findings show a substantial reduction of energy intake in the first year after bariatric surgery but do not support a link between lower energy intake and greater weight loss.

Plant-Derived Natural Products and Their Biomedical Properties: Recent Advances and Future Directions.

Nature has always been a source of inspiration and innovation to humanity [...].

The Role of Plant-Derived Natural Products in the Management of Inflammatory Bowel Disease-What Is the Clinical Evidence So Far?

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are a major healthcare challenge worldwide. Disturbances in the immune system and gut microbiota followed by environmental triggers are thought to be part of the aetiological factors. Current treatment for IBD includes corticosteroids, immunosuppressants, and other biologic agents; however, some patients are still unresponsive, and these are also linked to high financial load and severe side effects. Plant-derived natural products are rich in phytochemicals and have been used as healing agents in several diseases since antiquity due to their antioxidant, anti-inflammatory, and immunomodulatory properties, as well as gut microbiota modulation. Numerous in vitro and in vivo studies have shown that phytochemicals act in key pathways that are associated with the pathogenesis of IBD. It is also reported that the use of plant-derived natural products as complementary treatments is increasing amongst patients with IBD to avoid the side effects accompanying standard medical treatment. This review summarises the relevant evidence around the use of plant-derived natural products in the management of IBD, with specific focus on the clinical evidence so far for Curcumin, Mastiha, Boswellia serrata, and Artemisia absinthium.

Clinical and inflammatory biomarkers of inflammatory bowel diseases are linked to plasma trace elements and toxic metals; new insights into an old concept.

Background: Inflammatory bowel diseases (IBD) are chronic immune-mediated diseases, mainly represented by Crohn's disease (CD) and ulcerative colitis (UC). Several environmental factors have been proposed to contribute to disease pathogenesis, amongst which are metals. These can affect the immune system and may be associated with IBD. The aim of the present cross-sectional study was to investigate blood levels of metals in IBD patients and to examine possible associations with clinical and inflammatory disease markers. Methods: In total, 76 CD patients, 39 UC patients and 38 healthy controls were included. Blood and stool samples were collected. Metals were quantified in plasma samples using inductively coupled plasma mass spectrometry. Results: There were more abnormalities of circulating metals in CD than in UC when compared to healthy controls. CD: Concentrations of the essential trace elements zinc and selenium were lower in CD patients than the controls. Chromium was negatively associated with serum IL-6 (Beta: -3.558, p = 0.011), and caesium with fecal calprotectin (Beta: -0.481, p = 0.038) and serum IL-10 (Beta: -1.912, p = 0.050). In contrast, copper was positively associated with C-reactive protein (Beta: 2.548 × 102, p = 0.033). UC: In UC, a negative association of iron with serum myeloperoxidase levels (Beta: -1.270 × 103, p = 0.044) was detected. Thallium, a hazardous metal, however, was positively associated with disease activity (Beta: 3.899, p = < 0.01). Conclusion: In conclusion, our study offers new insights into the relations of metals with IBD. Further research should focus on the evaluation of the above associations and potential underlying mechanisms.

Linking the IL-17A immune response with NMR-based faecal metabolic profile in IBD patients treated with Mastiha.

Dysregulation of intestinal immune response plays a critical role in the pathogenesis of Inflammatory Bowel Disease (IBD). Mastiha's anti-inflammatory properties are well established. Our aim was to investigate Mastiha's regulatory effect on IL-17A serum levels in IBD patients. Alterations of the faecal metabolome as a functional readout of microbial activity were explored. A randomized, double-blind, placebo-controlled, parallel-group design was applied for a total of 3 months in active and 6 months in inactive IBD patients. Serum IL-17A increased significantly in Mastiha group (p = 0.006), and the mean change differed significantly between Mastiha and placebo (p = 0.003) even after adjusting for age, sex and BMI (p = 0.001) in inactive patients. In inactive UC patients IL-17A decreased significantly only in placebo (p = 0.033). No significant differences were detected in active disease. Faecal metabolomics indicated that intervention with Mastiha influenced considerably the metabolic profile of IBD patients in remission exhibiting, in between others, increased levels of glycine and tryptophan. Glycine has been proposed to have a therapeutic effect against IBD, while tryptophan derivatives are involved in immunoregalutory mechanisms, such as the Th17 cells differentiation. Thus, it is quite possible that the immunoregulatory role of Mastiha in quiescent IBD involves the regulation of Th17 cells function and differentiation.

An Absorption and Plasma Kinetics Study of Monoterpenes Present in Mastiha Oil in Humans.

Monoterpenes are bioactive compounds, however studies on their metabolic fate in humans are scarce. The present work aimed to identify and quantify the bioactive monoterpenes myrcene, α- and ß-pinene of the Mediterranean product Mastiha Oil, in human plasma after acute consumption of a single dose. This was an open-label, single-arm acute study. After overnight fasting, healthy males were administered with Mastiha Oil. Blood samples were collected on different time-points before and after consumption. A novel GC-MS-MS application was performed to detect and quantify terpenes in MO and in plasma. Serum lipid resistance to oxidation was also determined. Alpha-Pinene, ß-pinene and myrcene were identified and quantified in plasma. Alpha-pinene concentration significantly increased after 0.5 h of Mastiha Oil consumption, remaining significantly increased at 1 h, 2 h, 4 h, 6 h and 24 h. Beta-pinene and myrcene followed similar patterns. The increase in serum lipid resistance to oxidation was significant at 1 h, reached its peak at 2 h and remained significant until 4 h. Conclusively, α-pinene, ß-pinene and myrcene that are present in Mastiha Oil are absorbed by humans. (ClinicalTrials.gov Identifier: NCT04290312).

The Association of Plasma-Free Branched-Chain Amino Acids with Disease Related Parameters in Ulcerative Colitis.

Branched-chain amino acids (BCAAs) are involved in immune system's metabolic pathways and play fundamental role in gut health. Our aim was to assess BCAA plasma levels in patients with ulcerative colitis (UC) and associations of plasma BCAAs with disease-related parameters. This was a case-control study in adult patients with UC and BMI-matched controls. A total of 150 volunteers were screened between May 2016 and June 2017; 43 patients and 34 healthy controls were enrolled. Medical and dietary history (3 × 24 h recalls, MedDiet score), anthropometric measurements, blood and fecal samples were collected. We measured BCAAs in plasma with gas chromatography-mass spectrometry. In patients, fecal calprotectin, lactoferrin, lysozyme and defensin were quantified. Dietary pattern was similar in patients and controls. Plasma-free BCAA profiles did not differ between groups. Regression analysis showed that i) valine was inversely associated with calprotectin (p = 0.007) and ii) isoleucine with age (p = 0.031), after adjusting for age, sex, PMS and smoking. Leucine was negatively associated with age (p = 0.015) after adjusting for age, sex and PMS, but this association vanished when smoking was introduced. No correlation was observed between total BCAAs with any of the parameters. Plasma-free valine is negatively associated with calprotectin in patients with UC.

Serum Vitamins D, B9 and B12 in Greek Patients with Inflammatory Bowel Diseases.

Deficiencies in vitamin D, folate and cobalamin are common in Inflammatory Bowel Disease (IBD). The aim of the present study was to assess serum levels of these vitamins in IBD adults based on the respective serum cut off values for vitamin deficiencies, and to explore possible associations with IBD-related biomarkers and nutritional intake. A cross-sectional study was carried out and patients with Crohn's disease (CD) or ulcerative colitis (UC) from Attica-Greece were enrolled. Medical and dietary history, clinical examination and blood/stool biomarkers were evaluated. In total, 87 patients participated in the study. Serum levels of 25(OH)D, folate and cobalamin were deficient in 36.8%, 18.4% and 5.7% of patients, respectively. Linear regression analysis in the overall patients showed positive associations between (a) serum 25(OH)D with serum iron (beta = 0.083, p = 0.005) and (b) serum cobalamin with total bilirubin (beta = 0.357, p = 0.020) and direct bilirubin (beta = 0.727, p = 0.033), adjusting for age, sex, body mass index (BMI), disease activity and duration, smoking, nutritional intake and season of recruitment. In CD patients (N = 54), a negative linear association between serum folate and fecal lysozyme was evident (beta = -0.009, p = 0.020). No associations were found for UC patients (N = 33). The serum vitamin profile may be a complementary biomarker for the evaluation of disease activity next to serum and stool inflammatory biomarkers.

Antioxidant and Anti-Inflammatory Properties of Mastiha: A Review of Preclinical and Clinical Studies.

Nowadays both scientists and consumers have an increasing interest for natural products as preventing and healing factors without side effects. Mastiha, is a natural product of the Mediterranean basin with several health benefits as investigated the last decades. The present review summarises the research evidence from preclinical and clinical studies regarding the antioxidant and anti-inflammatory potential of Mastiha. MEDLINE, COHRANE and search terms "Mastiha", "Mastic gum", "Chios mastic" and "Pistacia lentiscus" were used. We limited our search by selecting only articles written in English literature, published between 2003 and 2019 that were experimental studies on Mastiha resinous exudate (review articles and individual case reports were excluded). Additional searches were performed using "oxidative stress" and "inflammation". A total of 19 studies met our criteria and were included in this review. Currently, there are more preclinical than clinical data available. Taken all together, the antioxidant potential of Mastiha is most probably owed to the inhibition of protein kinase, while its anti-inflammatory capacity may be the result of the inhibition of NF-κB activation. Further clinical studies in large populations are necessary.

Plasma free amino acid profile in quiescent Inflammatory Bowel Disease patients orally administered with Mastiha (Pistacia lentiscus); a randomised clinical trial.

BACKGROUND: Natural products have been studied regarding their effectiveness on Inflammatory Bowel Disease (IBD). HYPOTHESIS/PURPOSE: To examine the effects of Mastiha (Pistacia lentiscus var. Chia) on clinical course and amino acid (AA) profile of patients in remission. STUDY DESIGN: This is a randomised, double-blind, placebo-controlled clinical trial. METHODS: Patients (n = 68) were randomly allocated to Mastiha (2.8  g/day) or placebo adjunct to stable medication. Free AAs were identified applying Gas Chromatography-Mass Spectrometry in plasma. Medical-dietary history, Inflammatory Bowel Disease Questionnaire, Harvey-Bradshaw Index, Partial Mayo Score, biochemical, faecal and blood inflammatory markers were assessed. Primary endpoint was the clinical relapse rate at 6 months. Secondary endpoints included variations in free AAs, inflammatory biomarkers and quality of life. Statistical significance was set at 0.05. RESULTS: Concerning AAs and biochemical data, alanine (p = 0.006), valine (p = 0.047), proline (p = 0.022), glutamine (p < 0.001) and tyrosine (p = 0.043) along with total cholesterol (p = 0.032) and LDL cholesterol (p = 0.045) increased only in placebo group compared with baseline and the change between the study groups was significantly different. Inflammatory markers had not a significantly different change between the two groups, even serum IL-6, faecal calprotectin and faecal lactoferrin increased only in the placebo group. Although Mastiha was not proven superior to placebo in remission rate (17.6% vs. 23.5%, p = 0.549), attenuation in increase of free AAs levels in verum group is reported. CONCLUSION: Mastiha inhibited an increase in plasma free AAs seen in patients with quiescent IBD. Since change of AAs is considered an early prognostic marker of disease activity, this indicates a potential role of Mastiha in remission maintenance.

Mastiha (Pistacia lentiscus) Improves Gut Microbiota Diversity, Hepatic Steatosis, and Disease Activity in a Biopsy-Confirmed Mouse Model of Advanced Non-Alcoholic Steatohepatitis and Fibrosis.

SCOPE: As a result of the obesity epidemic, the prevalence of non-alcoholic steatohepatitis (NASH) is increasing. No drug is approved for the treatment of NASH. In this study, the effect of a nutritional supplement, Mastiha or Chios mastic gum, on metabolic and histological parameters and on the gut microbiome in mice with NASH and fibrosis was investigated. METHODS AND RESULTS: Advanced NASH was induced by feeding C57BL/6J mice a diet rich in fat, sucrose, and cholesterol for 41 weeks. After randomization, animals received the NASH-inducing diet with or without 0.2% (w/w) Mastiha for a further 8 weeks. Disease activity was assessed by liver histology and determination of plasma transaminase activities. Fecal microbiota DNA extraction and 16S rRNA amplicon sequencing were used to determine the composition of the gut microbiome. Mastiha supplementation led to a significant reduction in circulating alanine aminotransferase (ALT) activity, improvement in hepatic steatosis and collagen content, and a reduction in NAFLD activity score. Furthermore, it resulted in a partial but significant recovery of gut microbiota diversity and changes in identity and abundance of specific taxa. CONCLUSION: This is the first study demonstrating an improvement in disease activity in mice with advanced NASH with fibrosis by a diet containing Mastiha.

Modulation of Free Amino Acid Profile in Healthy Humans Administered with Mastiha Terpenes. An Open-Label Trial.

We aimed to explore whether plasma-free amino acids are modified in response to terpenes administration in healthy humans. In this open-label, single-arm acute trial, seventeen healthy male volunteers were administered with a naturally occurring product of known terpenes-namely mastiha-after overnight fasting. Blood samples were collected at different time points before and after ingestion. We aimed at identifying and quantifying 60 free amino acids in plasma applying Gas Chromatography-Mass Spectrometry. A total of 24 free amino acids were quantified. Branched-chain valine significantly decreased 4 h post-ingestion, whereas proline decreased at 6 h and ornithine at 2 h, compared to 0 h. These novel findings demonstrate that free amino acids levels are modulated in response to terpenes intake in healthy subjects.

Antioxidative Efficacy of a Pistacia Lentiscus Supplement and Its Effect on the Plasma Amino Acid Profile in Inflammatory Bowel Disease: A Randomised, Double-Blind, Placebo-Controlled Trial.

Oxidative stress is present in patients with Inflammatory Bowel Disease (IBD), and natural supplements with antioxidant properties have been investigated as a non-pharmacological approach. The objective of the present study was to assess the effects of a natural Pistacia lentiscus (PL) supplement on oxidative stress biomarkers and to characterise the plasma-free amino acid (AA) profiles of patients with active IBD (Crohn's disease (CD) N = 40, ulcerative colitis (UC) N = 20). The activity was determined according to 5 ≤ Harvey Bradshaw Index ≤ 16 or 2 ≤ Partial Mayo Score ≤ 6. This is a randomised, double-blind, placebo-controlled clinical trial. IBD patients (N = 60) were randomly allocated to PL (2.8 g/day) or to placebo for 3 months being under no treatment (N = 21) or under stable medical treatment (mesalamine N = 24, azathioprine N = 14, and corticosteroids N = 23) that was either single medication (N = 22) or combined medication (N = 17). Plasma oxidised, low-density lipoprotein (oxLDL), total serum oxidisability, and serum uric acid were evaluated at baseline and follow-up. OxLDL/LDL and oxLDL/High-Density Lipoprotein (HDL) ratios were calculated. The plasma-free AA profile was determined by applying a gas chromatography/mass spectrometry analysis. oxLDL (p = 0.031), oxLDL/HDL (p = 0.020), and oxLDL/LDL (p = 0.005) decreased significantly in the intervention group. The mean change differed significantly in CD between groups for oxLDL/LDL (p = 0.01), and, in the total sample, both oxLDL/LDL (p = 0.015) and oxLDL/HDL (p = 0.044) differed significantly. Several changes were reported in AA levels. PL ameliorated a decrease in plasma-free AAs seen in patients with UC taking placebo. In conclusion, this intervention resulted in favourable changes in oxidative stress biomarkers in active IBD.