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.

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.

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.

Dietary Patterns, Cardiometabolic and Lifestyle Variables in Greeks with Obesity and Metabolic Disorders.

There is considerable evidence that some dietary patterns contribute to obesity and metabolic disorders but there is less data on diet's association with different health parameters. We investigated the interaction between different dietary patterns and anthropometric, biochemical, lifestyle, and psychological health parameters in a Greek population with obesity and metabolic disorders. To the best of our knowledge, this is the first study in Greece with a thorough and holistic approach in analyzing such relationships. For assessing food patterns, revealing underlying structures, and reducing the number of variables we applied exploratory factor analysis (EFA). Principal Component Analysis was chosen as the extraction method using Varimax rotation, and three regression sets were computed. The study involved 146 Greek metabolically unhealthy obese adults, both men and women. Our cohort was categorized into four dietary patterns: "Western type diet", "Mediterranean-like diet", "Healthy diet", and "Animal meat and sauces diet". Dietary patterns characterized by a high consumption of energy-dense and animal-derived foods were positively associated with anthropometric and biochemical parameters related to metabolic disorders. Plant-based, healthier dietary patterns, on the other hand, were associated with better biochemical and mental health profiles among metabolically unhealthy obese individuals.

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.

Effect of Mastiha supplementation on NAFLD: The MAST4HEALTH Randomised, Controlled Trial.

SCOPE: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease with poor therapeutic strategies. Mastiha possesses antioxidant/anti-inflammatory and lipid-lowering properties. The authors investigate the effectiveness of Mastiha as a nonpharmacological intervention in NAFLD. METHODS AND RESULTS: Ninety-eight patients with NAFLD in three countries (Greece, Italy, Serbia) are randomly allocated to either Mastiha or Placebo for 6 months, as part of a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The authors assess NAFLD severity via magnetic resonance imaging (MRI) scanning and LiverMultiScan technique and evaluate the effectiveness of Mastiha through medical, anthropometric, biochemical, metabolomic, and microbiota assessment. Mastiha is not superior to Placebo on changes in iron-corrected T1 (cT1) and Liver Inflammation Fibrosis score (LIF) in entire patient population; however, after BMI stratification (BMI ≤ 35 kg m-2 and BMI > 35 kg m-2 ), severely obese patients show an improvement in cT1 and LIF in Mastiha versus Placebo. Mastiha increases dissimilarity of gut microbiota, as shown by the Bray-Curtis index, downregulates Flavonifractor, a known inflammatory taxon and decreases Lysophosphatidylcholines-(LysoPC) 18:1, Lysophosphatidylethanolamines-(LysoPE) 18:1, and cholic acid compared to Placebo. CONCLUSION: Mastiha supplementation improves microbiota dysbiosis and lipid metabolite levels in patients with NAFLD, although it reduces parameters of liver inflammation/fibrosis only in severely obese patients.

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.

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.

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.

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.

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.