The Effect of Melatonin Supplementation on Cancer-Related Fatigue during Chemotherapy Treatment of Breast Cancer Patients: A Double-Blind, Randomized Controlled Study.

Cancer-related fatigue (CRF) is a common distressing complaint of breast cancer (BC) patients treated with chemotherapy. Nutritional quality plays a pivotal role in CRF, while increased interest towards new pharmacological agents has been observed. Melatonin, an endogenous hormone that regulates the human sleep-wake cycle, could alleviate CRF. In the present randomized, placebo-controlled 3-month trial, we investigated the effects of melatonin intake (i.e., 1 mg/day) vs. placebo in BC patients on CRF. In both arms, the Mediterranean diet (MD) was implemented. Medical history, anthropometry and blood withdrawal were performed. CRF was evaluated by the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire and MD adherence by the MedDietScore. In total, 49 BC women (median age 52 years) were recruited, namely N = 23 in the intervention arm and N = 26 in the placebo arm. At baseline, CRF was positively associated with body mass index (BMI), even when adjusted for age, waist circumference and blood indices related to disease prognosis (beta = -0.882, p = 0.003). At 3 months, both groups showed a BMI decrease (p < 0.05), but only the intervention group improved CRF compared to baseline (p = 0.003). No differences in CRF were observed between the groups. In conclusion, melatonin oral supplementation could ameliorate CRF in BC patients.

Circulating Copper Is Associated with Inflammatory Biomarkers in Greek Older Adults with Osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis, that causes a significant decrease in the quality of life of the afflicted and constitutes a great burden for the socioeconomic system. Trace elements and heavy metals are implicated in the pathophysiology of OA, exacerbating inflammatory and oxidative stress responses. The aim of this cross-sectional study was to quantify metals in plasma samples of Greek OA patients and explore their link with disease related parameters, health status or quality of life, as well as epigenetic OA markers. This is the first study on plasma metal levels in Greek knee OA patients. To achieve precision in plasma metal and miRNA measurements, high-quality samples were selected from a subset of 34 participants (NCT04783792). Demographic, quality of life, clinical, biochemical, inflammation, oxidative stress, and anthropometric parameters, as well as microRNA levels were assessed. Significant correlations were found between circulating metals with OA related parameters or with measured microRNAs. Also, significant positive associations between plasma copper (Cu) levels and CRP (p = 0.033) or IL-6 (p = 0.001) occurred when adjusting for age, gender, BMI, physical activity level, smoking, disease severity, total arthroplasty, and dietary intake of the respective metal. Cu's role in OA is bidirectional, and this study confirms the findings that in OA, Cu is positively associated with inflammation. Such relationships between lifestyle, environment and OA enhance our understanding and encourage further study on metals related to OA inflammation.

Vanadium, cobalt, zinc, and rubidium are associated with markers of inflammation and oxidative stress in a Greek population with obesity.

Introduction: The prevalence of obesity is rising globally, with negative effects on the socioeconomic system. As a result of its drivers which include low-grade chronic inflammation, oxidative stress, and fatty acid metabolism, this phenotype develops metabolic anomalies that exacerbate its pathogenesis. It has been discovered that metals and metalloids have substantial effects on both the immune system and metabolism and are influenced by factors connected to obesity. Although there is a known connection between metals, obesity, and related metabolic disorders, it is still under research. Methods: We determined the plasma levels of 16 metals and metalloids in 76 individuals with obesity and investigated the relationships with inflammatory and oxidative stress biomarkers in order to clarify the processes by which metals/metalloids exhibit their effects. Results: After adjusting for age, gender, BMI, physical activity level, smoking, the existence of metabolic abnormalities, and dietary intake of the corresponding metal, regression analysis revealed the following statistically significant associations; vanadium was negatively associated with oxLDL (Beta ± SE= -0.014 ± 0.005, p=0.007), zinc was negatively associated with leptin (Beta ± SE= -12.390 ± 5.226, p=0.025), cobalt was associated negatively with adiponectin (Beta ± SE= -0.030 ± 0.012, p=0.001) and positively with MPO (Beta ± SE= 0.002 ± 0.001, p=0.023), and rubidium was negatively associated with oxLDL (Beta ± SE= -1.139 ± 0.411, p=0.008) and positively with MPO (Beta ± SE= 0.324 ± 0.102, p=0.003). Discussion: The aforementioned associations highlight the need for further research, demonstrating the importance of inflammation and oxidative stress in the association between metals/metalloids and obesity-related metabolic abnormalities.

A standardized nutraceutical supplement contributes to pain relief, improves quality of life and regulates inflammation in knee osteoarthritis patients; A randomized clinical trial.

Osteoarthritis (OA) is a degenerative disease of the joints that affects greatly the elderly population and the health care systems and is on the increase due to aging and obesity. Interventions aim at palliative care and pharmaceutical therapies entail serious adverse events. Whereas polyphenols constitute a promising holistic approach in the arsenal of physicians, trials investigating biomarkers and questionnaires are scarce. As such, a randomized controlled trial (RCT) was conducted to evaluate the potency of a standardized polyphenolic supplement in the management of systemic inflammation, oxidative stress, pain and general quality of life (QoL) in patients with osteoarthritis. Sixty subjects were randomized to receive either a polyphenol supplement (curcuma phospholipid, rosemary extract, resveratrol, ascorbic acid), or an active comparator (ascorbic acid) twice, daily for 12 weeks. The group that received the polyphenols exhibited significantly lower symptoms of pain and improved physical function and QoL as it was depicted by validated questionnaires, compared to the control group. Furthermore, post intervention, inflammation was restrained in the polyphenol group. Since systemic inflammation promotes local inflammation, the decrease of pain herein might be attributed to the attenuation of systemic inflammation by the polyphenols.

Identifying novel regulatory effects for clinically relevant genes through the study of the Greek population.

BACKGROUND: Expression quantitative trait loci (eQTL) studies provide insights into regulatory mechanisms underlying disease risk. Expanding studies of gene regulation to underexplored populations and to medically relevant tissues offers potential to reveal yet unknown regulatory variants and to better understand disease mechanisms. Here, we performed eQTL mapping in subcutaneous (S) and visceral (V) adipose tissue from 106 Greek individuals (Greek Metabolic study, GM) and compared our findings to those from the Genotype-Tissue Expression (GTEx) resource. RESULTS: We identified 1,930 and 1,515 eGenes in S and V respectively, over 13% of which are not observed in GTEx adipose tissue, and that do not arise due to different ancestry. We report additional context-specific regulatory effects in genes of clinical interest (e.g. oncogene ST7) and in genes regulating responses to environmental stimuli (e.g. MIR21, SNX33). We suggest that a fraction of the reported differences across populations is due to environmental effects on gene expression, driving context-specific eQTLs, and suggest that environmental effects can determine the penetrance of disease variants thus shaping disease risk. We report that over half of GM eQTLs colocalize with GWAS SNPs and of these colocalizations 41% are not detected in GTEx. We also highlight the clinical relevance of S adipose tissue by revealing that inflammatory processes are upregulated in individuals with obesity, not only in V, but also in S tissue. CONCLUSIONS: By focusing on an understudied population, our results provide further candidate genes for investigation regarding their role in adipose tissue biology and their contribution to disease risk and pathogenesis.

Peripheral inflammation is linked with emotion and mental health in people with obesity. A "head to toe" observational study.

Background: Obesity is a significant worldwide health problem that is linked with mental health. The elucidation of the possible overlapping biochemical mechanism(s) involved in inflammation and oxidative stress is imperative to better understand and address obesity and related metabolic disorders. The aim of the study was to investigate the associations between inflammatory and oxidative stress profiles with parameters that reflect metabolic, emotional, and mental health in a Greek metabolically unhealthy obese cohort. Methods: In total, 122 metabolically unhealthy people with obesity were recruited. Anthropometric measurements, biochemical, inflammatory and oxidative stress markers were assessed. Quality of life was evaluated through questionnaires for insomnia, self-esteem, depression, physical and mental health. Results: The inflammatory biomarker tumor necrosis factor-alpha (TNF-α) and the ratio oxidized low-density lipoprotein/low-density lipoprotein (oxLDL/LDL) were higher in hypertensive (p=0.002, p=0.001 respectively) and hyperglycemic subjects (p=0.017, p=0.001 respectively). Furthermore TNF-α (p<0.001), oxLDL/LDL (p<0.001) and oxLDL/high-density lipoprotein (HDL) (p=0.016) increased significantly with the increase of metabolic syndrome components. Finally, a negative association between interleukin-6 (IL-6) and Rosenberg Self-Esteem Scale (Beta=-0.019, p=0.019) and a positive association between TNF-α and the Center for Epidemiologic Studies Depression Scale Revised (Beta=0.003, p=0.015) were found. Conclusions: The results of the study suggest that obesity-related systemic inflammation is associated with worse self-esteem and depression symptoms, indicating an overlapping mechanism which can be utilized to the management of obesity.

Artemisia arborescens and Artemisia inculta from Crete; Secondary Metabolites, Trace Metals and In Vitro Antioxidant Activities.

BACKGROUND: Currently, the use of medicinal plants has increased. Artemisia species have been used in several applications, including medicinal use and uses in cosmetics, foods and beverages. Artemisia arborescens L. and Artemisia inculta are part of the Mediterranean diet in the form of aqueous infusions. Herein, we aimed to compare the secondary metabolites of the decoctions and two different extracts (methanolic and aqueous-glycerolic) of these two species, as well as their antioxidant capacity and trace metal levels. METHODS: Total phenolic, total flavonoid, total terpenes, total hydroxycinnamate, total flavonol, total anthocyanin contents and antioxidant/antiradical activity were determined, and GC/MS analysis was applied to identify and quantify phenolics and terpenoids. Trace metals were quantified with ICP-MS. RESULTS: Aqueous-glycerolic extracts demonstrated higher levels of total secondary metabolites, greater antioxidant potential and higher terpenoid levels than decoctions and methanolic extracts. Subsequently, the aqueous-glycerolic extract of a particularly high phenolic content was further analyzed applying targeted LC-MS/MS as the most appropriate analytic tool for the determination of the phenolic profile. Overall, twenty-two metabolites were identified. The potential contribution of infusions consumption to metal intake was additionally evaluated, and did not exceed the recommended daily intake. CONCLUSIONS: Our results support the use of these two species in several food, cosmetic or pharmaceutical applications.

Chios mastiha essential oil exhibits antihypertensive, hypolipidemic and anti-obesity effects in metabolically unhealthy adults - a randomized controlled trial.

The essential oil of the resinous exudate from Pistacia lentiscus of Chios namely Chios Mastiha Essential Oil (CMEO), is a natural volatile oil rich in monoterpenes α-pinene, ß-myrcene, ß-pinene. In the present randomized controlled trial, we investigated the effects of CMEO on individuals with abdominal obesity and metabolic abnormalities i.e., dyslipidemia, hypertension, insulin resistance. Eligible patients (N = 94) were randomly assigned to either the intervention group, receiving capsules containing 200 mg of CMEO daily for 3 months adjunct to current treatment for metabolic disorder(s), or the control group. Anthropometric measurements, blood markers, and quality of life (QoL) were assessed. Statistical analysis was performed on an intention-to-treat basis. A significant improvement in blood lipid profile, namely triglycerides (p = 0.026) and low-density lipoprotein (p = 0.05) of the CMEO group versus controls was observed. Systolic blood pressure (p = 0.05) and alanine aminotransferase (p = 0.022) significantly decreased only after CMEO intake. Alike, weight decreased only in CMEO (p = 0.02), while mean changes in % body fat (p = 0.005) and visceral fat (p = 0.045) were significantly different between groups post-intervention. Lower oxidized LDL (p = 0.044) and higher adiponectin (p = 0.007) were recorded in CMEO with significant different mean changes between groups post-intervention. QoL, as assessed by Short Form-12 questionnaire was improved in the CMEO compared to control (p = 0.041 for Physical Composite Score, p = 0.035 for Mental Composite Score). No adverse effects were reported. An anti-obesity effect of CMEO, probably attributed to modulation of inflammatory and antioxidant processes, is suggested. Conclusively, CMEO can be safe and effective in regulating metabolic abnormalities, adjunct to treatment. (ClinicalTrials.gov. The effect of Mastiha oil in Metabolic Syndrome, ID Number: NCT04785573).

Dietary Patterns and Nutritional Value in Non-Communicable Diseases.

Non-communicable diseases (NCDs) constitute the leading cause of mortality worldwide, with the four major contributors being cardiovascular diseases (CVDs), cancers, respiratory diseases, and diabetes [...].

Association of Dietary Patterns with MRI Markers of Hepatic Inflammation and Fibrosis in the MAST4HEALTH Study.

Whereas the etiology of non-alcoholic fatty liver disease (NAFLD) is complex, the role of nutrition as a causing and preventive factor is not fully explored. The aim of this study is to associate dietary patterns with magnetic resonance imaging (MRI) parameters in a European population (Greece, Italy, and Serbia) affected by NAFLD. For the first time, iron-corrected T1 (cT1), proton density fat fraction (PDFF), and the liver inflammation fibrosis score (LIF) were examined in relation to diet. A total of 97 obese patients with NAFLD from the MAST4HEALTH study were included in the analysis. A validated semi-quantitative food frequency questionnaire (FFQ) was used to assess the quality of diet and food combinations. Other variables investigated include anthropometric measurements, total type 2 diabetes risk, physical activity level (PAL), and smoking status. Principal component analysis (PCA) was performed to identify dietary patterns. Six dietary patterns were identified, namely "High-Sugar", "Prudent", "Western", "High-Fat and Salt", "Plant-Based", and "Low-Fat Dairy and Poultry". The "Western" pattern was positively associated with cT1 in the unadjusted model (beta: 0.020, p-value: 0.025) and even after adjusting for age, sex, body mass index (BMI), PAL, smoking, the center of the study, and the other five dietary patterns (beta: 0.024, p-value: 0.020). On the contrary, compared with low-intake patients, those with medium intake of the "Low-Fat Dairy and Poultry" pattern were associated with lower values of cT1, PDFF, and LIF. However, patients with a "Low-Fat Dairy and Poultry" dietary pattern were negatively associated with MRI parameters (cT1: beta: -0.052, p-value: 0.046, PDFF: beta: -0.448, p-value: 0.030, LIF: beta: -0.408, p-value: 0.025). Our findings indicate several associations between MRI parameters and dietary patterns in NAFLD patients, highlighting the importance of diet in NAFLD.

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.

Nutrigenetic Interactions Might Modulate the Antioxidant and Anti-Inflammatory Status in Mastiha-Supplemented Patients With NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease with no therapeutic consensus. Oxidation and inflammation are hallmarks in the progression of this complex disease, which also involves interactions between the genetic background and the environment. Mastiha is a natural nutritional supplement known to possess antioxidant and anti-inflammatory properties. This study investigated how a 6-month Mastiha supplementation (2.1 g/day) could impact the antioxidant and inflammatory status of patients with NAFLD, and whether genetic variants significantly mediate these effects. We recruited 98 patients with obesity (BMI ≥ 30 kg/m2) and NAFLD and randomly allocated them to either the Mastiha or the placebo group for 6 months. The anti-oxidative and inflammatory status was assessed at baseline and post-treatment. Genome-wide genetic data was also obtained from all participants, to investigate gene-by-Mastiha interactions. NAFLD patients with severe obesity (BMI > 35kg/m2) taking the Mastiha had significantly higher total antioxidant status (TAS) compared to the corresponding placebo group (P value=0.008). We did not observe any other significant change in the investigated biomarkers as a result of Mastiha supplementation alone. We identified several novel gene-by-Mastiha interaction associations with levels of cytokines and antioxidant biomarkers. Some of the identified genetic loci are implicated in the pathological pathways of NAFLD, including the lanosterol synthase gene (LSS) associated with glutathione peroxidase activity (Gpx) levels, the mitochondrial pyruvate carrier-1 gene (MPC1) and the sphingolipid transporter-1 gene (SPNS1) associated with hemoglobin levels, the transforming growth factor-beta-induced gene (TGFBI) and the micro-RNA 129-1 (MIR129-1) associated with IL-6 and the granzyme B gene (GZMB) associated with IL-10 levels. Within the MAST4HEALTH randomized clinical trial (NCT03135873, www.clinicaltrials.gov) Mastiha supplementation improved the TAS levels among NAFLD patients with severe obesity. We identified several novel genome-wide significant nutrigenetic interactions, influencing the antioxidant and inflammatory status in NAFLD. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03135873.

Dietary Interventions with Polyphenols in Osteoarthritis: A Systematic Review Directed from the Preclinical Data to Randomized Clinical Studies.

Osteoarthritis (OA) is the most common form of arthritis and a major cause of limited functionality and thus a decrease in the quality of life of the inflicted. Given the fact that the existing pharmacological treatments lack disease-modifying properties and their use entails significant side effects, nutraceuticals with bioactive compounds constitute an interesting field of research. Polyphenols are plant-derived molecules with established anti-inflammatory and antioxidant properties that have been extensively evaluated in clinical settings and preclinical models in OA. As more knowledge is gained in the research field, an interesting approach in the management of OA is the additive and/or synergistic effects that polyphenols may have in an optimized supplement. Therefore, the aim of this review was to summarize the recent literature regarding the use of combined polyphenols in the management of OA. For that purpose, a PubMed literature survey was conducted with a focus on some preclinical osteoarthritis models and randomized clinical trials on patients with osteoarthritis from 2018 to 2021 which have evaluated the effect of combinations of polyphenol-rich extracts and purified polyphenol constituents. Data indicate that combined polyphenols may be promising for the treatment of osteoarthritis in the future, but more clinical trials with novel approaches in the identification of the in-between relationship of such constituents are needed.

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.

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.

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 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.

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.

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.

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.