The Potential of Integrative Cancer Treatment Using Melatonin and the Challenge of Heterogeneity in Population-Based Studies: A Case Report of Colon Cancer and a Literature Review.

Melatonin is a multifunctional hormone regulator that maintains homeostasis through circadian rhythms, and desynchronization of these rhythms can lead to gastrointestinal disorders and increase the risk of cancer. Preliminary clinical studies have shown that exogenous melatonin alleviates the harmful effects of anticancer therapy and improves quality of life, but the results are still inconclusive due to the heterogeneity of the studies. A personalized approach to testing clinical parameters and response to integrative treatment with nontoxic and bioavailable melatonin in patient-centered N-of-1 studies deserves greater attention. This clinical case of colon cancer analyzes and discusses the tumor pathology, the adverse effects of chemotherapy, and the dynamics of markers of inflammation (NLR, LMR, and PLR ratios), tumors (CEA, CA 19-9, and PSA), and hemostasis (D-dimer and activated partial thromboplastin time). The patient took melatonin during and after chemotherapy, nutrients (zinc, selenium, vitamin D, green tea, and taxifolin), and aspirin after chemotherapy. The patient's PSA levels decreased during CT combined with melatonin (19 mg/day), and melatonin normalized inflammatory markers and alleviated symptoms of polyneuropathy but did not help with thrombocytopenia. The results are analyzed and discussed in the context of the literature on oncostatic and systemic effects, alleviating therapy-mediated adverse effects, association with survival, and N-of-1 studies.

Associations of whole blood polyunsaturated fatty acids and insulin resistance among European children and adolescents.

This study aims to examine the association of whole blood n-3 and n-6 polyunsaturated fatty acids (PUFA) with insulin resistance (IR) in children. Whole blood fatty acids were measured in 705 children aged 2-9 years of the European IDEFICS/I.Family cohort using gas chromatography in units of weight percentage of all detected fatty acids (%wt/wt). IR was determined by the Homeostasis Model Assessment for IR (HOMA). Mixed effect models were used to assess the associations between selected baseline PUFA and HOMA z-scores at baseline and after 2- and 6-year follow-ups using models with basic and additional confounder adjustment as well as stratified by sex and weight status. In the basic model, α-linolenic (ß = 1.46 SD/%wt/wt, p = 0.006) and eicosapentaenoic acid (ß = 1.17 SD/%wt/wt, p = 0.001) were positively associated with baseline HOMA z-score. In the stratified analyses, α-linolenic acid was positively associated with HOMA z-score in girls only (ß = 1.98 SD/%wt/wt, p = 0.006) and arachidonic acid was inversely associated with baseline HOMA in thin/normal-weight children (ß = - 0.13 SD/%wt/wt, p = 0.0063). In the fully adjusted model, no statistically significant associations were seen.Conclusions: Our overall results do not indicate a protective role of higher blood n-3 PUFA or an adverse role of higher blood arachidonic acid proportion on the risk of IR. What is Known: •Intervention studies reported a beneficial effect of n-3 PUFA supplementation on insulin resistance compared with placebo while observational studies in cildren are inconclusive. •Studies have shown a positive association of n-6 arachidonic acid and insulin resistance indicating an adverse role of arachidonic acid. What is New: •Cross-sectional and longitudinal analyses based on circulating blood fatty acid concentrations in a large cohort of European children and adolescents. •Overall results do not support a protective role of n-3 PUFA or an adverse role of arachidonic acid in insulin resistance.

Use of Nutritional Supplements in Youth with Medicated and Unmedicated Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To find out whether use of nutritional supplements (NUS) differs between children and adolescents with attention-deficit/hyperactivity disorder (ADHD; medicated or unmedicated), compared with those without the disorder. METHODS: We used cross-sectional data from the population-based I.Family study conducted between 2013 and 2014 in eight European countries. Parents completed questionnaires and participated in interviews, for example, on health and medical history of their child. Data from 5067 children and adolescents aged 5-17 years were included. Exposures were medicated (with ADHD-approved medication) and unmedicated ADHD. The outcome was the use of NUS, measured by use of any or multiple different NUS. Multivariable logistic regression adjusted for sociodemographics and health determinants was used to find ADHD-depending differences. RESULTS: The study sample comprised 4490 children and adolescents without ADHD and 51 medicated and 76 unmedicated subjects with ADHD. Regarding the use of any NUS, no statistically significant differences were found between children and adolescents without ADHD (18%) and those with medicated (18%) or unmedicated ADHD (22%). However, discrepancies appear when considering multiple use of NUS, not reported for any medicated ADHD subject but remarkably often for unmedicated ADHD subjects (13%), resulting in an adjusted odds ratio of 2.6 (95% confidence interval, 1.2-5.6) when compared with those without ADHD (5%). CONCLUSION: Children and adolescents who were not using medication for treating ADHD potentially took NUS as oral remedies. Given the potential for a delay of indicated treatments and for use of those NUS which have no proven effectiveness, pediatricians should actively explore whether NUS have been used to treat ADHD core symptoms, and families should be informed that the average effect size has to be considered small.

Associations of Whole Blood n-3 and n-6 Polyunsaturated Fatty Acids with Blood Pressure in Children and Adolescents - Results from the IDEFICS/I.Family Cohort.

BACKGROUND: Polyunsaturated n-3 and n-6 polyunsaturated fatty acids (PUFA) are precursors of biologically active metabolites that affect blood pressure (BP) regulation. This study investigated the association of n-3 and n-6 PUFA and BP in children and adolescents. METHODS: In a subsample of 1267 children aged 2-9 years at baseline of the European IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) cohort whole blood fatty acids were measured by a validated gas chromatographic method. Systolic and diastolic BP was measured at baseline and after two and six years. Mixed-effects models were used to assess the associations between fatty acids at baseline and BP z-scores over time adjusting for relevant covariables. Models were further estimated stratified by sex and weight status. RESULTS: The baseline level of arachidonic acid was positively associated with subsequent systolic BP (ß = 0.08, P = 0.002) and diastolic BP (ß = 0.07, P<0.001). In thin/normal weight children, baseline alpha-linolenic (ß = -1.13, P = 0.003) and eicosapentaenoic acid (ß = -0.85, P = 0.003) levels were inversely related to baseline and also to subsequent systolic BP and alpha-linolenic acid to subsequent diastolic BP. In overweight/obese children, baseline eicosapentaenoic acid level was positively associated with baseline diastolic BP (ß = 0.54, P = 0.005). CONCLUSIONS: Low blood arachidonic acid levels in the whole sample and high n-3 PUFA levels in thin/normal weight children are associated with lower and therefore healthier BP. The beneficial effects of high n-3 PUFA on BP were not observed in overweight/obese children, suggesting that they may have been overlaid by the unfavorable effects of excess weight.