1 6872 167 [POLYPHENOLS AS PROMISING BIOACTIVE COMPOUNDS]. POLYPHENOLS ARE DIVERSE AND WIDESPREAD BIOACTIVE PLANT-BASED COMPOUNDS. THESE COMPOUNDS ARE FOUND IN VARIOUS FOODS SUCH AS BERRIES, FRUITS, VEGETABLES, CEREALS, NUTS, COFFEE, CACAO, SPICES, SEEDS. THEY ARE DIVIDED INTO PHENOLIC ACIDS, STILBENES, FLAVONOIDS, LIGNANS DEPENDING ON THEIR MOLECULAR STRUCTURE. THEY ATTRACT THE ATTENTION OF RESEARCHERS DUE TO WIDE RANGE OF BIOLOGICAL EFFECTS ON HUMAN BODY. THE PURPOSE OF THIS WORK WAS TO ANALYZE MODERN SCIENTIFIC PUBLICATIONS ON THE BIOLOGICAL EFFECTS OF POLYPHENOLS. MATERIAL AND METHODS. THE REVIEW IS BASED ON PUBLICATIONS PRESENTED IN THE PUBMED, GOOGLE SCHOLAR, RESEARCHGATE, ELSEVIER, ELIBRARY, CYBERLENINKA DATABASES USING "POLYPHENOLS", "FLAVONOIDS", "RESVERATROL", "QUERCETIN", "CATECHINS" AS KEY WORDS. PREFERENCE WAS GIVEN TO ORIGINAL RESEARCHES OVER THE PAST 10 YEARS PUBLISHED IN REFEREED JOURNALS. RESULTS. OXIDATIVE STRESS, CHRONIC INFLAMMATION, MICROBIOME DISORDERS, INSULIN RESISTANCE, EXCESSIVE PROTEIN GLYCATION, AND GENOTOXIC EFFECTS ARE AT THE HEART OF THE PATHOGENESIS OF MANY DISEASES, INCLUDING THOSE ASSOCIATED WITH AGE. A LARGE AMOUNT OF MATERIAL HAS BEEN ACCUMULATED ON THE ANTIOXIDANT, ANTICARCINOGENIC, EPIGENETIC, METABOLIC, GEROPROTECTIVE, ANTI-INFLAMMATORY AND ANTIVIRAL EFFECTS OF POLYPHENOLS. THIS GIVES REASONS TO CONSIDER POLYPHENOLS AS VERY PROMISING MICRONUTRIENTS, WHICH INCLUSION IN THE DIET CAN REDUCE THE RISK OF DEVELOPING CARDIOVASCULAR, ONCOLOGICAL, NEURODEGENERATIVE DISEASES, DIABETES MELLITUS, OBESITY, METABOLIC SYNDROME, PREMATURE AGING, THAT IS, THE MAIN CAUSES OF DEATH, A DECREASE IN THE DURATION AND QUALITY OF LIFE OF A MODERN PERSON. CONCLUSION. EXPANDING THE RANGE OF PRODUCTS ENRICHED WITH POLYPHENOLS WITH THEIR HIGH BIOAVAILABILITY IS A PROMISING AREA OF SCIENTIFIC RESEARCH AND DEVELOPMENT OF PRODUCTION IN ORDER TO PREVENT SOCIALLY SIGNIFICANT AGE-ASSOCIATED DISEASES. 2023 2 4396 40 MODULATION OF CHRONIC INFLAMMATION BY QUERCETIN: THE BENEFICIAL EFFECTS ON OBESITY. OBESITY HAS BECOME A MAJOR RISK FACTOR FOR THE DEVELOPMENT OF CHRONIC DISEASES SUCH AS INSULIN RESISTANCE, TYPE 2 DIABETES MELLITUS, AND CARDIOVASCULAR DISEASE. MOREOVER, OBESITY INDUCES CHRONIC INFLAMMATION IN ADIPOSE TISSUE, LIVER, SKELETAL MUSCLE, AND THE VASCULAR SYSTEM. QUERCETIN IS THE MAJOR REPRESENTATIVE OF THE FLAVONOID SUBCLASS OF FLAVONOLS, WHICH IS UBIQUITOUSLY CONTAINED WITHIN NATURAL PLANTS SUCH AS GREEN TEA, AND VEGETABLES, INCLUDING ONIONS AND APPLES. RESEARCHERS HAVE FOCUSED GREATER ATTENTION TO THE BENEFICIAL PHYSIOLOGICAL ROLES OF QUERCETIN, WHICH HAS ANTI-OXIDATIVE, ANTI-INFLAMMATORY, AND ANTI-FIBROTIC EFFECTS ON INSULIN RESISTANCE AND ATHEROSCLEROSIS IN OBESITY-RELATED DISEASES. ALSO, THE ANTI-INFLAMMATORY EFFECTS OF QUERCETIN ON INTESTINAL MICROBIOTA HAVE BEEN DEMONSTRATED IN OBESITY. IN ADDITION, THERE IS INCREASING EVIDENCE THAT QUERCETIN IS ASSOCIATED WITH EPIGENETIC ACTIVITIES IN CANCER, AND IN MATERNAL UNDERNUTRITION DURING GESTATION AND LACTATION. IN THIS REVIEW, WE FOCUS ON THE CHEMICAL PROPERTIES OF QUERCETIN, ITS DIETARY SOURCES IN OBESITY, AND ITS ANTI-INFLAMMATORY EFFECTS ON INSULIN RESISTANCE, ATHEROSCLEROSIS, INTESTINAL MICROBIOTA, AND MATERNAL UNDER-NUTRITION WITH EPIGENETIC ACTIVITY. 2020 3 2100 32 EPIGENETIC EFFECTS OF NATURAL POLYPHENOLS: A FOCUS ON SIRT1-MEDIATED MECHANISMS. POLYPHENOLS ARE A CLASS OF NATURAL COMPOUNDS WIDELY DISTRIBUTED IN FRUITS, VEGETABLES, AND PLANTS. THEY HAVE BEEN REPORTED TO POSSESS A WIDE RANGE OF ACTIVITIES IN PREVENTION AND ALLEVIATION OF VARIOUS DISEASES LIKE CANCER, NEUROINFLAMMATION, DIABETES, AND AGING. POLYPHENOLS ARE EFFECTIVE AGAINST CHRONIC DISEASES AND RECENT REPORTS INDICATED STRONG EPIGENETIC EFFECTS OF POLYPHENOLS. MOST OF THE STUDIES INVESTIGATING EPIGENETIC EFFECTS OF NATURAL POLYPHENOLS HAVE FOCUSED ON THEIR BENEFICIAL EFFECTS IN CANCER TREATMENT. HOWEVER, EPIGENETIC DEFECTS HAVE BEEN DEMONSTRATED IN MANY OTHER DISEASES AS WELL, AND APPLICATION OF POLYPHENOLS TO MODULATE THE EPIGENOME IS BECOMING AN INTERESTING FIELD OF RESEARCH. THIS REVIEW SUMMARIZES THE EFFECTS OF NATURAL POLYPHENOLS IN MODULATING EPIGENETIC-RELATED ENZYMES AS WELL AS THEIR EFFECT IN PREVENTION AND TREATMENT OF CHRONIC DISEASES WITH A FOCUS ON SIRT1 MODULATION. WE HAVE ALSO DISCUSSED THE RELATION BETWEEN THE STRUCTURE AND FUNCTION OF EPIGENETIC-MODIFYING POLYPHENOLS. 2014 4 2424 38 EPIGENETIC SIGNATURES UNDERLYING INFLAMMATION: AN INTERPLAY OF NUTRITION, PHYSICAL ACTIVITY, METABOLIC DISEASES, AND ENVIRONMENTAL FACTORS FOR PERSONALIZED NUTRITION. AIM AND OBJECTIVE: EMERGING TRANSLATIONAL EVIDENCE SUGGESTS THAT EPIGENETIC ALTERATIONS (DNA METHYLATION, MIRNA EXPRESSION, AND HISTONE MODIFICATIONS) OCCUR AFTER EXTERNAL STIMULI AND MAY CONTRIBUTE TO EXACERBATED INFLAMMATION AND THE RISK OF SUFFERING SEVERAL DISEASES INCLUDING DIABETES, CARDIOVASCULAR DISEASES, CANCER, AND NEUROLOGICAL DISORDERS. THIS REVIEW SUMMARIZES THE CURRENT KNOWLEDGE ABOUT THE HARMFUL EFFECTS OF HIGH-FAT/HIGH-SUGAR DIETS, MICRONUTRIENT DEFICIENCIES (FOLATE, MANGANESE, AND CAROTENOIDS), OBESITY AND ASSOCIATED COMPLICATIONS, BACTERIAL/VIRAL INFECTIONS, SMOKING, EXCESSIVE ALCOHOL CONSUMPTION, SLEEP DEPRIVATION, CHRONIC STRESS, AIR POLLUTION, AND CHEMICAL EXPOSURE ON INFLAMMATION THROUGH EPIGENETIC MECHANISMS. ADDITIONALLY, THE EPIGENETIC PHENOMENA UNDERLYING THE ANTI-INFLAMMATORY POTENTIAL OF CALORIC RESTRICTION, N-3 PUFA, MEDITERRANEAN DIET, VITAMIN D, ZINC, POLYPHENOLS (I.E., RESVERATROL, GALLIC ACID, EPICATECHIN, LUTEOLIN, CURCUMIN), AND THE ROLE OF SYSTEMATIC EXERCISE ARE DISCUSSED. METHODS: ORIGINAL AND REVIEW ARTICLES ENCOMPASSING EPIGENETICS AND INFLAMMATION WERE SCREENED FROM MAJOR DATABASES (INCLUDING PUBMED, MEDLINE, SCIENCE DIRECT, SCOPUS, ETC.) AND ANALYZED FOR THE WRITING OF THE REVIEW PAPER. CONCLUSION: ALTHOUGH CAUTION SHOULD BE EXERCISED, RESEARCH ON EPIGENETIC MECHANISMS IS CONTRIBUTING TO UNDERSTAND PATHOLOGICAL PROCESSES INVOLVING INFLAMMATORY RESPONSES, THE PREDICTION OF DISEASE RISK BASED ON THE EPIGENOTYPE, AS WELL AS THE PUTATIVE DESIGN OF THERAPEUTIC INTERVENTIONS TARGETING THE EPIGENOME. 2021 5 4652 33 NEUROPROTECTION WITH NATURAL ANTIOXIDANTS AND NUTRACEUTICALS IN THE CONTEXT OF BRAIN CELL DEGENERATION: THE EPIGENETIC CONNECTION. BIOACTIVE ANTIOXIDANT AGENTS PRESENT IN SELECTED PLANTS ARE KNOWN TO PROVIDE THE FIRST LINE OF BIOLOGICAL DEFENSE AGAINST OXIDATIVE STRESS. IN PARTICULAR, SOLUBLE VITAMIN C, E, CAROTENOIDS AND PHENOLIC COMPOUNDS HAVE DEMONSTRATED CRUCIAL BIOLOGICAL EFFECTS IN CELLS AGAINST OXIDATIVE DAMAGE, PREVENTING PREVALENT CHRONIC DISEASES, SUCH AS DIABETES, CANCER AND CARDIOVASCULAR DISEASE. THE REPORTED WIDE RANGE OF EFFECTS THAT INCLUDED ANTI-AGING, ANTI-ATHEROSCLEROSIS, ANTI-INFLAMMATORY AND ANTICANCER ACTIVITY WERE STUDIED AGAINST DEGENERATIVE PATHOLOGIES OF THE BRAIN. VITAMINS AND DIFFERENT PHYTOCHEMICALS ARE IMPORTANT EPIGENETIC MODIFIERS THAT PREVENT NEURODEGENERATION. IN ORDER TO EXPLORE THE POTENTIAL ANTIOXIDANT SOURCES IN FUNCTIONAL FOODS AND NUTRACEUTICALS AGAINST NEURODEGENERATION, THE PRESENT PAPER AIMS TO SHOW A COMPREHENSIVE ASSESSMENT OF ANTIOXIDANT ACTIVITY AT CHEMICAL AND CELLULAR LEVELS. THE EFFECTS OF THE DIFFERENT BIOACTIVE COMPOUNDS AVAILABLE AND THEIR ANTIOXIDANT ACTIVITY THROUGH AN EPIGENETIC POINT OF VIEW ARE ALSO DISCUSSED. 2019 6 6379 31 THE ROLE OF NUTRITION ON META-INFLAMMATION: INSIGHTS AND POTENTIAL TARGETS IN COMMUNICABLE AND CHRONIC DISEASE MANAGEMENT. PURPOSE OF REVIEW: CHRONIC LOW-GRADE INFLAMMATION MAY CONTRIBUTE TO THE ONSET AND PROGRESSION OF COMMUNICABLE AND CHRONIC DISEASES. THIS REVIEW EXAMINED THE EFFECTS AND EVENTUAL MEDIATION ROLES OF DIFFERENT NUTRITIONAL FACTORS ON INFLAMMATION. RECENT FINDINGS: POTENTIAL NUTRITIONAL COMPOUNDS INFLUENCING INFLAMMATION PROCESSES INCLUDE MACRO AND MICRONUTRIENTS, BIOACTIVE MOLECULES (POLYPHENOLS), SPECIFIC FOOD COMPONENTS, AND CULINARY INGREDIENTS AS WELL AS STANDARDIZED DIETARY PATTERNS, EATING HABITS, AND CHRONONUTRITION FEATURES. THEREFORE, RESEARCH IN THIS FIELD IS STILL REQUIRED, TAKING INTO ACCOUNT CRITICAL ASPECTS OF HETEROGENEITY INCLUDING TYPE OF POPULATION, MINIMUM AND MAXIMUM INTAKES AND ADVERSE EFFECTS, COOKING METHODS, PHYSIOPATHOLOGICAL STATUS, AND TIMES OF INTERVENTION. MOREOVER, THE INTEGRATIVE ANALYSIS OF TRADITIONAL VARIABLES (AGE, SEX, METABOLIC PROFILE, CLINICAL HISTORY, BODY PHENOTYPE, HABITUAL DIETARY INTAKE, PHYSICAL ACTIVITY LEVELS, AND LIFESTYLE) TOGETHER WITH INDIVIDUALIZED ISSUES (GENETIC BACKGROUND, EPIGENETIC SIGNATURES, MICROBIOTA COMPOSITION, GENE EXPRESSION PROFILES, AND METABOLOMIC FINGERPRINTS) MAY CONTRIBUTE TO THE KNOWLEDGE AND PRESCRIPTION OF MORE PERSONALIZED TREATMENTS AIMED TO IMPROVING THE PRECISION MEDICAL MANAGEMENT OF INFLAMMATION AS WELL AS THE DESIGN OF ANTI-INFLAMMATORY DIETS IN CHRONIC AND COMMUNICABLE DISEASES. 2022 7 1414 35 DIETARY PHYTOCHEMICALS IN NEUROIMMUNOAGING: A NEW THERAPEUTIC POSSIBILITY FOR HUMANS? ALTHOUGH SEVERAL EFFORTS HAVE BEEN MADE IN THE SEARCH FOR GENETIC AND EPIGENETIC PATTERNS LINKED TO DISEASES, A COMPREHENSIVE EXPLANATION OF THE MECHANISMS UNDERLYING PATHOLOGICAL PHENOTYPIC PLASTICITY IS STILL FAR FROM BEING CLARIFIED. OXIDATIVE STRESS AND INFLAMMATION ARE TWO OF THE MAJOR TRIGGERS OF THE EPIGENETIC ALTERATIONS OCCURRING IN CHRONIC PATHOLOGIES, SUCH AS NEURODEGENERATIVE DISEASES. IN FACT, OVER THE LAST DECADE, REMARKABLE PROGRESS HAS BEEN MADE TO REALIZE THAT CHRONIC, LOW-GRADE INFLAMMATION IS ONE OF THE MAJOR RISK FACTOR UNDERLYING BRAIN AGING. ACCUMULATED DATA STRONGLY SUGGEST THAT PHYTOCHEMICALS FROM FRUITS, VEGETABLES, HERBS, AND SPICES MAY EXERT RELEVANT IMMUNOMODULATORY AND/OR ANTI-INFLAMMATORY ACTIVITIES IN THE CONTEXT OF BRAIN AGING. STARTING BY THE EVIDENCE THAT A COMMON DENOMINATOR OF AGING AND CHRONIC DEGENERATIVE DISEASES IS REPRESENTED BY INFLAMMATION, AND THAT SEVERAL DIETARY PHYTOCHEMICALS ARE ABLE TO POTENTIALLY INTERFERE WITH AND REGULATE THE NORMAL FUNCTION OF CELLS, IN PARTICULAR NEURONAL COMPONENTS, AIM OF THIS REVIEW IS TO SUMMARIZE RECENT STUDIES ON NEUROINFLAMMAGING PROCESSES AND PROOFS INDICATING THAT SPECIFIC PHYTOCHEMICALS MAY ACT AS POSITIVE MODULATORS OF NEUROINFLAMMATORY EVENTS. IN ADDITION, CRITICAL PATHWAYS INVOLVED IN MEDIATING PHYTOCHEMICALS EFFECTS ON NEUROINFLAMMAGING WERE DISCUSSED, EXPLORING THE REAL IMPACT OF THESE COMPOUNDS IN PRESERVING BRAIN HEALTH BEFORE THE ONSET OF SYMPTOMS LEADING TO INFLAMMATORY NEURODEGENERATION AND COGNITIVE DECLINE. 2016 8 617 39 BIOACTIVE FOOD COMPOUNDS, EPIGENETICS AND CHRONIC DISEASE PREVENTION: FOCUS ON EARLY-LIFE INTERVENTIONS WITH POLYPHENOLS. CONSUMPTION OF BIOACTIVE COMPOUNDS SUCH AS POLYPHENOLS, ISOTHIOCYANATES, SULFUR-CONTAINING COMPOUNDS AND TERPENOIDS, FOUND IN FRUITS AND VEGETABLES, IS ASSOCIATED WITH PREVENTION OF CHRONIC DISEASE. THESE BIOACTIVE FOOD COMPOUNDS ELICIT THEIR PROTECTIVE EFFECTS THROUGH COMPLEX MECHANISMS AT THE CELLULAR AND MOLECULAR, INCLUDING EPIGENETIC LEVELS. ACCORDING TO THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) PARADIGM, IN UTERO EXPOSURE TO STRESSORS SUCH AS MALNUTRITION THROUGH MATERNAL DIET WOULD IMPAIR FETAL DEVELOPMENT AND EPIGENETICALLY PROGRAM INCREASED RISK OF METABOLIC DISEASES AND SOME CANCERS IN ADULT LIFE. IN ADDITION, A ROLE FOR FATHERS DIET DURING PRECONCEPTION ON THEIR OFFSPRING HEALTH AND CHRONIC DISEASE SUSCEPTIBILITY HAS ALSO EMERGED. THIS HIGHLIGHTS EARLY LIFE AS A PROMISING WINDOW OF OPPORTUNITY FOR STARTING DIETARY INTERVENTIONS FOCUSING ON PREVENTING CHRONIC DISEASES. HOWEVER, KNOWLEDGE ON THE POTENTIAL BENEFICIAL IMPACT OF EARLY LIFE EXPOSURE TO BIOACTIVE FOOD COMPOUNDS IS LIMITED. AMONG THE STUDIES THAT HAVE INVESTIGATED BIOACTIVE FOOD COMPOUNDS IN THE CONTEXT OF DOHAD, MOST HAVE FOCUSED ON THE IMPACT OF DIETARY POLYPHENOLS. THUS, IN THIS REVIEW WE DISCUSS EXPERIMENTAL EVIDENCE SUPPORTING A ROLE FOR THE DIETARY POLYPHENOLS RESVERATROL, GENISTEIN, EPIGALLOCATECHIN-3-GALLATE AND ANTHOCYANINS IN CHRONIC DISEASE PREVENTION CONSIDERING A PERSPECTIVE FROM EARLY-LIFE INTERVENTIONS THROUGH MATERNAL AND PATERNAL DIETS AND FOCUSING ON EPIGENETICS AS A POTENTIAL UNDERLYING MECHANISM. 2019 9 6258 38 THE MOLECULAR MECHANISM OF POLYPHENOLS IN THE REGULATION OF AGEING HALLMARKS. AGEING IS A COMPLEX PROCESS CHARACTERIZED MAINLY BY A DECLINE IN THE FUNCTION OF CELLS, TISSUES, AND ORGANS, RESULTING IN AN INCREASED RISK OF MORTALITY. THIS PROCESS INVOLVES SEVERAL CHANGES, DESCRIBED AS HALLMARKS OF AGEING, WHICH INCLUDE GENOMIC INSTABILITY, TELOMERE ATTRITION, EPIGENETIC CHANGES, LOSS OF PROTEOSTASIS, DYSREGULATED NUTRIENT SENSING, MITOCHONDRIAL DYSFUNCTION, CELLULAR SENESCENCE, STEM CELL DEPLETION, AND ALTERED INTRACELLULAR COMMUNICATION. THE DETERMINING ROLE THAT ENVIRONMENTAL FACTORS SUCH AS DIET AND LIFESTYLE PLAY ON HEALTH, LIFE EXPECTANCY, AND SUSCEPTIBILITY TO DISEASES, INCLUDING CANCER AND NEURODEGENERATIVE DISEASES, IS WELLESTABLISHED. IN VIEW OF THE GROWING INTEREST IN THE BENEFICIAL EFFECTS OF PHYTOCHEMICALS IN THE PREVENTION OF CHRONIC DISEASES, SEVERAL STUDIES HAVE BEEN CONDUCTED, AND THEY STRONGLY SUGGEST THAT THE INTAKE OF DIETARY POLYPHENOLS MAY BRING NUMEROUS BENEFITS DUE TO THEIR ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES, AND THEIR INTAKE HAS BEEN ASSOCIATED WITH IMPAIRED AGEING IN HUMANS. POLYPHENOL INTAKE HAS BEEN SHOWN TO BE EFFECTIVE IN AMELIORATING SEVERAL AGE-RELATED PHENOTYPES, INCLUDING OXIDATIVE STRESS, INFLAMMATORY PROCESSES, IMPAIRED PROTEOSTASIS, AND CELLULAR SENESCENCE, AMONG OTHER FEATURES, WHICH CONTRIBUTE TO AN INCREASED RISK OF AGEING-ASSOCIATED DISEASES. THIS REVIEW AIMS TO ADDRESS, IN A GENERAL WAY, THE MAIN FINDINGS DESCRIBED IN THE LITERATURE ABOUT THE BENEFITS OF POLYPHENOLS IN EACH OF THE HALLMARKS OF AGEING, AS WELL AS THE MAIN REGULATORY MECHANISMS RESPONSIBLE FOR THE OBSERVED ANTIAGEING EFFECTS. 2023 10 6380 30 THE ROLE OF OBESITY AND DIABETES IN DEMENTIA. CHRONIC CONDITIONS SUCH AS OBESITY, DIABETES, AND DEMENTIA ARE INCREASING IN THE UNITED STATES (US) POPULATION. KNOWLEDGE OF THESE CHRONIC CONDITIONS, PREVENTATIVE MEASURES, AND PROPER MANAGEMENT TACTICS IS IMPORTANT AND CRITICAL TO PREVENTING DISEASE. THE OVERLAP BETWEEN OBESITY, DIABETES, AND DEMENTIA IS BECOMING FURTHER ELUCIDATED. THESE CONDITIONS SHARE A SIMILAR ORIGIN THROUGH THE COMPONENTS OF INCREASING AGE, GENDER, GENETIC AND EPIGENETIC PREDISPOSITIONS, DEPRESSION, AND A HIGH-FAT WESTERN DIET (WD) THAT ALL CONTRIBUTE TO THE INFLAMMATORY STATE ASSOCIATED WITH THE DEVELOPMENT OF OBESITY, DIABETES, AND DEMENTIA. THIS INFLAMMATORY STATE LEADS TO THE DYSREGULATION OF FOOD INTAKE AND INSULIN RESISTANCE. OBESITY IS OFTEN THE CORNERSTONE THAT LEADS TO THE DEVELOPMENT OF DIABETES AND, SUBSEQUENTLY, IN THE CASE OF TYPE 2 DIABETES MELLITUS (T2DM), PROGRESSION TO "TYPE 3 DIABETES MELLITUS (T3DM)". OBESITY AND DEPRESSION ARE CLOSELY ASSOCIATED WITH DIABETES. HOWEVER, DEMENTIA CAN BE AVOIDED WITH LIFESTYLE MODIFICATIONS, BY SWITCHING TO A PLANT-BASED DIET (E.G., A MEDITERRANEAN DIET (MD)), AND INCREASING PHYSICAL ACTIVITY. DIET AND EXERCISE ARE NOT THE ONLY TREATMENT OPTIONS. THERE ARE SEVERAL SURGICAL AND PHARMACOLOGICAL INTERVENTIONS AVAILABLE FOR PREVENTION. CURRENT AND FUTURE RESEARCH WITHIN EACH OF THESE FIELDS IS WARRANTED AND OFFERS THE CHANCE FOR NEW TREATMENT OPTIONS AND A BETTER UNDERSTANDING OF THE PATHOGENESIS OF EACH CONDITION. 2022 11 1410 34 DIETARY INTERVENTIONS FOR AUTISM SPECTRUM DISORDER: AN UPDATED SYSTEMATIC REVIEW OF HUMAN STUDIES. AUTISM IS A COMPLEX SPECTRUM OF DISORDERS WITH GENETIC, EPIGENETIC, AUTOIMMUNE, OXIDATIVE STRESS, AND ENVIRONMENTAL ETIOLOGIES. TREATMENT OF ASD USING DIETARY APPROACH IS A PROMISING STRATEGY, ESPECIALLY OWING TO ITS SAFETY AND AVAILABILITY. OUR STUDY CRITICALLY ANALYSED THE ROLES AND EFFICACY OF ANTIOXIDANTS, PROBIOTICS, PREBIOTICS, CAMEL MILK AND VITAMIN D. THIS SYSTEMATIC REVIEW PROVIDES AN UPDATED SYNOPSIS OF HUMAN STUDIES THAT INVESTIGATED THERAPEUTIC BENEFITS OF THESE DIETARY INTERVENTIONS IN AUTISM. A TOTAL OF 943 PAPERS WERE IDENTIFIED OUT OF WHICH 21 ARTICLES WERE INCLUDED IN THE SYSTEMATIC REVIEW. THE SELECTED STUDIES INVESTIGATED THE IMPACT OF 5 DIFFERENT DIETARY SUPPLEMENTATIONS IN ASD SYMPTOM AND BEHAVIOURS. THESE AGENTS INCLUDE; ANTIOXIDANTS/POLYPHENOLIC COMPOUNDS, PROBIOTICS, PREBIOTICS, CAMEL MILK AND VITAMIN D. FROM THE RESULTS OF THE PRESENT REVIEW, ANTIOXIDANTS/POLYPHENOLIC COMPOUNDS DECREASED THE LEVELS OF INFLAMMATORY CYTOKINES AND IMPROVED BEHAVIOURAL SYMPTOMS. PROBIOTICS IMPROVED BEHAVIOURAL AND GI SYMPTOMS AS WELL AS RESTORED GUT MICROBIOTA EQUILIBRIUM. PREBIOTICS DECREASED LEVELS OF INFLAMMATORY CYTOKINES, IMPROVED BEHAVIOURAL AND GI SYMPTOMS AND IMPROVED GUT MICROBIOTA. VITAMIN D IMPROVED BEHAVIOURAL SYMPTOMS AND OFFERED PROTECTIVE EFFECTS AGAINST NEUROTOXICITY. CAMEL MILK REDUCED INFLAMMATORY RESPONSES AND OXIDATIVE STRESS. GIVEN THE CHRONIC NATURE AS WELL AS EARLY ONSET OF ASD, DIETARY SUPPLEMENTS BECOME USEFUL TO COMPLEMENT NUTRITIONAL DEFICIENCIES IN CHILDREN WITH ASD. KEY BENEFITS OF THESE AGENTS STEM FROM THEIR ABILITY TO TARGET MULTIPLE PHYSIOLOGICAL AREAS VIA THE GUT BRAIN-AXIS AND ARE DEVOID OF POTENTIAL HARMFUL OR AGGRAVATING EFFECTS ON ASD PATIENTS. THE EVIDENCE COLLATED IN THIS REVIEW PROPOSE THAT DIETARY INTERVENTION MAY PROVIDE A NEW PLATFORM FOR THE MANAGEMENT OF AUTISM. 2022 12 1254 32 CURRENT PROGRESS ON THE MECHANISMS OF HYPERHOMOCYSTEINEMIA-INDUCED VASCULAR INJURY AND USE OF NATURAL POLYPHENOL COMPOUNDS. CARDIOVASCULAR DISEASE IS ONE OF THE MOST COMMON DISEASES IN THE ELDERLY POPULATION, AND ITS INCIDENCE HAS RAPIDLY INCREASED WITH THE PROLONGATION OF LIFE EXPECTANCY. HYPERHOMOCYSTEINEMIA IS AN INDEPENDENT RISK FACTOR FOR VARIOUS CARDIOVASCULAR DISEASES, INCLUDING ATHEROSCLEROSIS, AND DAMAGE TO VASCULAR FUNCTION PLAYS AN INITIAL ROLE IN ITS PATHOGENESIS. THIS REVIEW PRESENTS THE LATEST KNOWLEDGE ON THE MECHANISMS OF VASCULAR INJURY CAUSED BY HYPERHOMOCYSTEINEMIA, INCLUDING OXIDATIVE STRESS, ENDOPLASMIC RETICULUM STRESS, PROTEIN N-HOMOCYSTEINIZATION, AND EPIGENETIC MODIFICATION, AND DISCUSSES THE THERAPEUTIC TARGETS OF NATURAL POLYPHENOLS. STUDIES HAVE SHOWN THAT NATURAL POLYPHENOLS IN PLANTS CAN REDUCE HOMOCYSTEINE LEVELS AND REGULATE DNA METHYLATION BY ACTING ON OXIDATIVE STRESS AND ENDOPLASMIC RETICULUM STRESS-RELATED SIGNALING PATHWAYS, THUS IMPROVING HYPERHOMOCYSTEINEMIA-INDUCED VASCULAR INJURY. NATURAL POLYPHENOLS OBTAINED VIA DAILY DIET ARE SAFER AND HAVE MORE PRACTICAL SIGNIFICANCE IN THE PREVENTION AND TREATMENT OF CHRONIC DISEASES THAN TRADITIONAL DRUGS. 2021 13 1402 28 DIETARY ANTIOXIDANTS REMODEL DNA METHYLATION PATTERNS IN CHRONIC DISEASE. CHRONIC DISEASES ACCOUNT FOR OVER 60% OF ALL DEATHS WORLDWIDE ACCORDING TO THE WORLD HEALTH ORGANIZATION REPORTS. MAJORITY OF CASES ARE TRIGGERED BY ENVIRONMENTAL EXPOSURES THAT LEAD TO ABERRANT CHANGES IN THE EPIGENOME, SPECIFICALLY, THE DNA METHYLATION PATTERNS. THESE CHANGES RESULT IN ALTERED EXPRESSION OF GENE NETWORKS AND ACTIVITY OF SIGNALLING PATHWAYS. DIETARY ANTIOXIDANTS, INCLUDING CATECHINS, FLAVONOIDS, ANTHOCYANINS, STILBENES AND CAROTENOIDS, DEMONSTRATE BENEFITS IN THE PREVENTION AND/OR SUPPORT OF THERAPY IN CHRONIC DISEASES. THIS REVIEW PROVIDES A COMPREHENSIVE DISCUSSION OF POTENTIAL EPIGENETIC MECHANISMS OF ANTIOXIDANT COMPOUNDS IN REVERSING ALTERED PATTERNS OF DNA METHYLATION IN CHRONIC DISEASE. ANTIOXIDANTS REMODEL THE DNA METHYLATION PATTERNS THROUGH MULTIPLE MECHANISMS, INCLUDING REGULATION OF EPIGENETIC ENZYMES AND CHROMATIN REMODELLING COMPLEXES. THESE EFFECTS CAN FURTHER CONTRIBUTE TO ANTIOXIDANT PROPERTIES OF THE COMPOUNDS. ON THE OTHER HAND, DECREASE IN OXIDATIVE STRESS ITSELF CAN IMPACT DNA METHYLATION DELIVERING ADDITIONAL LINK BETWEEN ANTIOXIDANT MECHANISMS AND EPIGENETIC EFFECTS OF THE COMPOUNDS. LINKED ARTICLES: THIS ARTICLE IS PART OF A THEMED SECTION ON THE PHARMACOLOGY OF NUTRACEUTICALS. TO VIEW THE OTHER ARTICLES IN THIS SECTION VISIT HTTP://ONLINELIBRARY.WILEY.COM/DOI/10.1111/BPH.V177.6/ISSUETOC. 2020 14 2835 36 FOOD AS MEDICINE: TARGETING THE URAEMIC PHENOTYPE IN CHRONIC KIDNEY DISEASE. THE OBSERVATION THAT UNHEALTHY DIETS (THOSE THAT ARE LOW IN WHOLE GRAINS, FRUITS AND VEGETABLES, AND HIGH IN SUGAR, SALT, SATURATED FAT AND ULTRA-PROCESSED FOODS) ARE A MAJOR RISK FACTOR FOR POOR HEALTH OUTCOMES HAS BOOSTED INTEREST IN THE CONCEPT OF 'FOOD AS MEDICINE'. THIS CONCEPT IS ESPECIALLY RELEVANT TO METABOLIC DISEASES, SUCH AS CHRONIC KIDNEY DISEASE (CKD), IN WHICH DIETARY APPROACHES ARE ALREADY USED TO AMELIORATE METABOLIC AND NUTRITIONAL COMPLICATIONS. INCREASED AWARENESS THAT TOXIC URAEMIC METABOLITES ORIGINATE NOT ONLY FROM INTERMEDIARY METABOLISM BUT ALSO FROM GUT MICROBIAL METABOLISM, WHICH IS DIRECTLY INFLUENCED BY DIET, HAS FUELLED INTEREST IN THE POTENTIAL OF 'FOOD AS MEDICINE' APPROACHES IN CKD BEYOND THE CURRENT STRATEGIES OF PROTEIN, SODIUM AND PHOSPHATE RESTRICTION. BIOACTIVE NUTRIENTS CAN ALTER THE COMPOSITION AND METABOLISM OF THE MICROBIOTA, ACT AS MODULATORS OF TRANSCRIPTION FACTORS INVOLVED IN INFLAMMATION AND OXIDATIVE STRESS, MITIGATE MITOCHONDRIAL DYSFUNCTION, ACT AS SENOLYTICS AND IMPACT THE EPIGENOME BY ALTERING ONE-CARBON METABOLISM. AS GUT DYSBIOSIS, INFLAMMATION, OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION, PREMATURE AGEING AND EPIGENETIC CHANGES ARE COMMON FEATURES OF CKD, THESE FINDINGS SUGGEST THAT TAILORED, HEALTHY DIETS THAT INCLUDE BIOACTIVE NUTRIENTS AS PART OF THE FOODOME COULD POTENTIALLY BE USED TO PREVENT AND TREAT CKD AND ITS COMPLICATIONS. 2021 15 6858 19 [NUTRIGENOMICS, OBESITY AND PUBLIC HEALTH]. FUNCTIONAL GENOMICS WILL CHANGE KNOWLEDGE AND PRACTICE IN CLINICAL NUTRITION IN THE FORTHCOMING YEARS. THE POSSIBILITY OF PERFORMING AN INDIVIDUAL'S GENETIC PROFILE (GENETIC VARIATIONS AND EPIGENETIC MODIFICATIONS) AS WELL AS THE ABILITY OF ITS INTEGRATION IN A COMPLEX NETWORK OF METABOLIC INTERACTIONS REPRESENTS A HUGE CHALLENGE IN HUMAN NUTRITION. THE INFLUENCE OF NUTRIGENOMICS IN TERMS OF PREVENTION AND TREATMENT OF CHRONIC DISEASES, SUCH AS OBESITY, TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE IN A POPULATION LEVEL REMAINS UNDETERMINED FOR THE MOMENT. THE OPPORTUNITY OF NUTRITIONAL INTERVENTION IN CRITICAL STAGES OF DEVELOPMENT AND THE CHANCE OF CHANGING GENETIC SUSCEPTIBILITY TO DISEASES THROUGH DIET IN A PUBLIC HEALTH BASIS SHOULD LEAD THE FUTURE OF NUTRIGENOMICS BEYOND THE MERE DESIGN OF "PERSONALIZED" FUNCTIONAL FOOD OR DIETS. 2007 16 3593 39 IMPLICATION OF THE MEDITERRANEAN DIET ON THE HUMAN EPIGENOME. EPIGENETICS, DEFINED AS "HEREDITARY CHANGES IN GENE EXPRESSION THAT OCCUR WITHOUT ANY CHANGE IN THE DNA SEQUENCE", CONSISTS OF VARIOUS EPIGENETIC MARKS, INCLUDING DNA METHYLATION, HISTONE MODIFICATIONS, AND NON-CODING RNAS. THE EPIGENOME, WHICH HAS A DYNAMIC STRUCTURE IN RESPONSE TO INTRACELLULAR AND EXTRACELLULAR STIMULI, HAS A KEY ROLE IN THE CONTROL OF GENE ACTIVITY, SINCE IT IS LOCATED AT THE INTERSECTION OF CELLULAR INFORMATION ENCODED IN THE GENOME AND MOLECULAR/CHEMICAL INFORMATION OF EXTRACELLULAR ORIGIN. THE FOCUS SHIFT OF STUDIES TO EPIGENETIC REPROGRAMMING HAS LED TO THE FORMATION AND PROGRESSIVE IMPORTANCE OF A CONCEPT CALLED "NUTRIEPIGENETICS", WHOSE AIM IS TO PREVENT DISEASES BY INTERVENING ON NUTRITION STYLE. AMONG THE DIET TYPES ADOPTED IN THE WORLD, THE RENOWNED MEDITERRANEAN DIET (MD), BEING RICH IN UNSATURATED FATTY ACIDS AND CONTAINING HIGH LEVELS OF WHOLE GRAIN FOODS AND LARGE QUANTITIES OF FRUITS, VEGETABLES, AND LEGUMES, HAS SHOWN NUMEROUS ADVANTAGES IN EXCLUDING CHRONIC DISEASES. ADDITIONALLY, THE FACT THAT THIS DIET IS RICH IN POLYPHENOLS WITH HIGH ANTIOXIDANT AND ANTI-INFLAMMATORY PROPERTIES HAS AN UNDENIABLE EFFECT IN TURNING SOME CELLULAR PATHWAYS AGAINST THE DISEASE. IT IS ALSO APPARENT THAT THE EFFECTS OF POLYPHENOLS ON THE EPIGENOME CAUSE CHANGES IN MECHANISMS SUCH AS DNA METHYLATION AND HISTONE ACETYLATION/DEACETYLATION, WHICH HAVE A REGULATORY EFFECT ON GENE REGULATION. THIS REVIEW PRESENTS THE EFFECTS OF LONG-TERM CONSUMPTION OF NUTRIENTS FROM THE MD ON THE EPIGENOME AND DISCUSSES THE BENEFITS OF THIS DIET IN THE TREATMENT AND EVEN PREVENTION OF CHRONIC DISEASES. 2022 17 5586 27 ROLE OF PERSONALIZED NUTRITION IN CHRONIC-DEGENERATIVE DISEASES. HUMAN NUTRITION IS A BRANCH OF MEDICINE BASED ON FOODS BIOCHEMICAL INTERACTIONS WITH THE HUMAN BODY. THE PHENOTYPIC TRANSITION FROM HEALTH TO DISEASE STATUS CAN BE ATTRIBUTED TO CHANGES IN GENES AND/OR PROTEIN EXPRESSION. FOR THIS REASON, A NEW DISCIPLINE HAS BEEN DEVELOPED CALLED "-OMIC SCIENCE". IN THIS REVIEW, WE ANALYZED THE ROLE OF "-OMICS SCIENCES" (NUTRIGENETICS, NUTRIGENOMICS, PROTEOMICS AND METABOLOMICS) IN THE HEALTH STATUS AND AS POSSIBLE THERAPEUTIC TOOL IN CHRONIC DEGENERATIVE DISEASES. IN PARTICULAR, WE FOCUSED ON THE ROLE OF NUTRIGENETICS AND THE RELATIONSHIP BETWEEN EATING HABITS, CHANGES IN THE DNA SEQUENCE AND THE ONSET OF NUTRITION-RELATED DISEASES. MOREOVER, WE EXAMINED NUTRIGENOMICS AND THE EFFECT OF NUTRIENTS ON GENE EXPRESSION. WE PERUSED THE ROLE OF PROTEOMICS AND METABOLOMICS IN PERSONALIZED NUTRITION. IN THIS SCENARIO, WE ANALYZED ALSO HOW DYSBIOSIS OF GUT MICROBIOTA CAN INFLUENCE THE ONSET AND PROGRESSION OF CHRONIC DEGENERATIVE DISEASES. MOREOVER, NUTRIENTS INFLUENCING AND REGULATING GENE ACTIVITY, BOTH DIRECTLY AND INDIRECTLY, PAVES THE WAY FOR PERSONALIZED NUTRITION THAT PLAYS A KEY ROLE IN THE PREVENTION AND TREATMENT OF CHRONIC DEGENERATIVE DISEASES. 2019 18 1241 33 CURRENT AND FUTURE NUTRITIONAL STRATEGIES TO MODULATE INFLAMMATORY DYNAMICS IN METABOLIC DISORDERS. OBESITY, TYPE 2 DIABETES, AND OTHER METABOLIC DISORDERS HAVE A LARGE IMPACT ON GLOBAL HEALTH, ESPECIALLY IN WESTERN COUNTRIES. AN IMPORTANT HALLMARK OF METABOLIC DISORDERS IS CHRONIC LOW-GRADE INFLAMMATION. A KEY PLAYER IN CHRONIC LOW-GRADE INFLAMMATION IS DYSMETABOLISM, WHICH IS DEFINED AS THE INABILITY TO KEEP HOMEOSTASIS RESULTING IN LOSS OF LIPID CONTROL, OXIDATIVE STRESS, INFLAMMATION, AND INSULIN RESISTANCE. ALTHOUGH OFTEN NOT YET DETECTABLE IN THE CIRCULATION, CHRONIC LOW-GRADE INFLAMMATION CAN BE PRESENT IN ONE OR MULTIPLE ORGANS. THE RESPONSE TO A METABOLIC CHALLENGE CONTAINING LIPIDS MAY MAGNIFY DYSFUNCTIONALITIES AT THE TISSUE LEVEL, CAUSING AN OVERFLOW OF INFLAMMATORY MARKERS INTO THE CIRCULATION AND HENCE ALLOW DETECTION OF EARLY LOW-GRADE INFLAMMATION. HERE, WE SUMMARIZE THE EVIDENCE OF SUCCESSFUL APPLICATION OF METABOLIC CHALLENGE TESTS IN TYPE 2 DIABETES, METABOLIC SYNDROME, OBESITY, AND UNHEALTHY AGING. WE ALSO REVIEW HOW METABOLIC CHALLENGE TESTS HAVE BEEN SUCCESSFULLY APPLIED TO EVALUATE NUTRITIONAL INTERVENTION EFFECTS, INCLUDING AN "ANTI-INFLAMMATORY" MIXTURE, DARK CHOCOLATE, WHOLE GRAIN WHEAT AND OVERFEEDING. ADDITIONALLY, WE ELABORATE ON FUTURE STRATEGIES TO (RE)GAIN INFLAMMATORY FLEXIBILITY. THROUGH EPIGENETIC AND METABOLIC REGULATION, THE INFLAMMATORY RESPONSE MAY BE TRAINED BY REGULAR MILD AND METABOLIC TRIGGERS, WHICH CAN BE UNDERSTOOD FROM THE PERSPECTIVE OF TRAINED IMMUNITY, HORMESIS AND PRO-RESOLUTION. NEW STRATEGIES TO OPTIMIZE DYNAMICS OF INFLAMMATION MAY BECOME AVAILABLE. 2019 19 2869 35 FUNCTIONAL FOODS AND HEALTH EFFECTS: A NUTRITIONAL BIOCHEMISTRY PERSPECTIVE. BACKGROUND: INCREASED CONSUMER S INTEREST IN HEALTH HAS DRIVEN THE DEVELOPMENT OF FOODS THAT OFFER SPECIFIC BENEFICIAL EFFECTS. THE LIST OF FOODS AND INGREDIENTS INCLUDES ESSENTIAL AND NON-ESSENTIAL NUTRIENTS, PLANT AND MARINE COMPONENTS, WHOLE FOODS, MICROORGANISMS, MICROALGAE AND TECHNOLOGICAL APPROACHES. TRADITIONALLY, HEALTH OUTCOMES FOCUSSED ON THE PREVENTION OF CHRONIC DISEASES BUT HEALTH TARGETS HAVE EXPANDED TO COVER AREAS SUCH AS BRAIN HEALTH, INFLAMMATION, EYE HEALTH, WOMEN S HEALTH, HEALTHY AGEING AND BEAUTY. OBJECTIVE: THIS REVIEW HIGHLIGHTS, FROM A NUTRITIONAL BIOCHEMISTRY PERSPECTIVE, DIFFERENTIAL ASPECTS ON DESIGNING AND INTERPRETING HUMAN STUDIES TO SUPPORT THE HEALTH EFFECTS OF FUNCTIONAL FOODS. RESULTS: DESPITE THE AVAILABLE EVIDENCE FROM IN VITRO, ANIMAL AND OBSERVATIONAL STUDIES, WELLDESIGNED HUMAN STUDIES ARE NECESSARY TO SUPPORT THE HEALTH EFFECTS OF FUNCTIONAL FOODS. INTERVENTION TRIALS WITH FOODS ARE COMPLEX AS THEY IMPLY LIMITATIONS DUE TO METHODOLOGICAL, FOOD-RELATED AND HOST-RELATED FACTORS. THE USE OF RESPONSIVE, VALIDATED AND CLINICALLY RELEVANT MARKERS BECOMES ESSENTIAL EVEN THOUGH THERE IS A LACK OF RELIABLE BIOMARKERS OF EXPOSURE FOR MANY BIOACTIVES. FURTHERMORE, THE EFFECT OF MODULATING FACTORS SUCH AS SUBCLINICAL INFLAMMATION, GUT MICROBIOTA AND GENETIC VARIABILITY SHOULD BE TAKEN INTO ACCOUNT. MULTIPLE INDICATORS MAY PROVIDE A MORE RELIABLE ALTERNATIVE TO ASSESS PHYSIOLOGICAL PROCESSES WHILE EMERGING BIOMARKERS (MICRORNAS, EPIGENETIC CHANGES) CONSTITUTE A PROMISING APPROACH. ADDITIONALLY, THE MAGNITUDE OF THE CHANGE IS CRITICAL TO SUPPORT ANY HEALTH EFFECT ALTHOUGH INTERVENTIONS MAY HAVE A LIMITED CLINICAL IMPACT BUT BE EPIDEMIOLOGICALLY RELEVANT. ALSO, BASED ON THE AVAILABLE DATA, THE PREMISE THAT BIOACTIVESCONTAINING FOODS ARE SAFE MAY BE QUESTIONABLE. CONCLUSION: AN INTEGRATED APPROACH INCLUDING MULTIPLE BIOMARKERS, GENETIC VARIABILITY, EFFECT OF GUT MICROBIOTA AND RISK/BENEFIT ASSESSMENT SHOULD BE USED TO SUPPORT THE POTENTIAL HEALTH EFFECTS OF FUNCTIONAL FOODS. 2016 20 6730 40 WALK MORE, EAT LESS, DON'T STRESS. UNHEALTHY DIET, OBESITY, LACK OF PHYSICAL ACTIVITY, AND PSYCHOLOGIC STRESS ARE ASSOCIATED WITH INCREASED INFLAMMATION, OXIDATIVE STRESS, INSULIN RESISTANCE, AND DNA METHYLATION, WHICH ARE THE MAIN MECHANISMS OF CHRONIC DISEASES SUCH AS CANCER, HYPERTENSION, DIABETES, CARDIOVASCULAR DISEASE, AND ALZHEIMER'S DISEASE. IT HAS RECENTLY BEEN FOUND THAT HEALTHY DIET AND PHYSICAL ACTIVITY CAN REDUCE INFLAMMATORY MARKERS AND IMPROVE INSULIN SENSITIVITY RESULTING IN BETTER SURVIVORSHIP OUTCOMES IN PATIENTS WITH PROSTATE CANCER. AN "ANTI-INFLAMMATORY" LIFESTYLE, INCLUDING PHYSICAL ACTIVITY, HEALTHY BODY WEIGHT, HEALTHY DIET, AND STRESS REDUCTION, HAS BEEN ASSOCIATED WITH DECREASED CANCER RISK AND PROGRESSION. EPIGENETIC CHANGES DUE TO DNA METHYLATION AND ALTERED GENE EXPRESSION ASSOCIATED WITH UNHEALTHY LIFESTYLE CAN BE MODULATED BY HEALTHY BEHAVIORS. NATIONAL CENTER FOR COMPLEMENTARY AND INTEGRATIVE HEALTH (NCCIH) FOCUSES ON HEALTHY LIFESTYLE, AND IT SUPPORTS RESEARCH ON PSYCHOLOGIC AND PHYSICAL APPROACHES INCLUDING DIETARY SUPPLEMENTS AND PLANT-BASED PRODUCTS, AS WELL AS MIND AND BODY APPROACHES, SUCH AS YOGA, MASSAGE, MEDITATION, MINDFULNESS-BASED STRESS REDUCTION, AND ACUPUNCTURE. SEE RELATED ARTICLE BY LANGLAIS ET AL., P. 1760. 2022