1 1398 177 DIET, GUT MICROBIOME AND EPIGENETICS: EMERGING LINKS WITH INFLAMMATORY BOWEL DISEASES AND PROSPECTS FOR MANAGEMENT AND PREVENTION. INFLAMMATORY BOWEL DISEASES (IBD) REPRESENT A GROWING PUBLIC HEALTH CONCERN DUE TO INCREASING INCIDENCE WORLDWIDE. THE CURRENT NOTION ON THE PATHOGENESIS OF IBD IS THAT GENETICALLY SUSCEPTIBLE INDIVIDUALS DEVELOP INTOLERANCE TO DYSREGULATED GUT MICROFLORA (DYSBIOSIS) AND CHRONIC INFLAMMATION DEVELOPS AS A RESULT OF ENVIRONMENTAL TRIGGERS. AMONG THE ENVIRONMENTAL FACTORS ASSOCIATED WITH IBD, DIET PLAYS AN IMPORTANT ROLE IN MODULATING THE GUT MICROBIOME, INFLUENCING EPIGENETIC CHANGES, AND, THEREFORE, COULD BE APPLIED AS A THERAPEUTIC TOOL TO IMPROVE THE DISEASE COURSE. NEVERTHELESS, THE CURRENT DIETARY RECOMMENDATIONS FOR DISEASE PREVENTION AND MANAGEMENT ARE SCARCE AND HAVE WEAK EVIDENCE. THIS REVIEW SUMMARISES THE CURRENT KNOWLEDGE ON THE COMPLEX INTERACTIONS BETWEEN DIET, MICROBIOME AND EPIGENETICS IN IBD. WHEREAS AN OVERABUNDANCE OF CALORIES AND SOME MACRONUTRIENTS INCREASE GUT INFLAMMATION, SEVERAL MICRONUTRIENTS HAVE THE POTENTIAL TO MODULATE IT. IMMUNONUTRITION HAS EMERGED AS A NEW CONCEPT PUTTING FORWARD THE IMPORTANCE OF VITAMINS SUCH AS VITAMINS A, C, E, AND D, FOLIC ACID, BETA CAROTENE AND TRACE ELEMENTS SUCH AS ZINC, SELENIUM, MANGANESE AND IRON. HOWEVER, WHEN ASSESSED IN CLINICAL TRIALS, SPECIFIC MICRONUTRIENTS EXERTED A LIMITED BENEFIT. BEYOND NUTRIENTS, AN ANTI-INFLAMMATORY DIETARY PATTERN AS A COMPLEX INTERVENTION APPROACH HAS BECOME POPULAR IN RECENT YEARS. HENCE, EXCLUSIVE ENTERAL NUTRITION IN PAEDIATRIC CROHN'S DISEASE IS THE ONLY NUTRITIONAL INTERVENTION CURRENTLY RECOMMENDED AS A FIRST-LINE THERAPY. OTHER NUTRITIONAL INTERVENTIONS OR SPECIFIC DIETS INCLUDING THE SPECIFIC CARBOHYDRATE DIET (SCD), THE LOW FERMENTABLE OLIGOSACCHARIDES, DISACCHARIDES, MONOSACCHARIDES, AND POLYOL (FODMAP) DIET AND, MOST RECENTLY, THE MEDITERRANEAN DIET HAVE SHOWN STRONG ANTI-INFLAMMATORY PROPERTIES AND SHOW PROMISE FOR IMPROVING DISEASE SYMPTOMS. MORE WORK IS REQUIRED TO EVALUATE THE ROLE OF INDIVIDUAL FOOD COMPOUNDS AND COMPLEX NUTRITIONAL INTERVENTIONS WITH THE POTENTIAL TO DECREASE INFLAMMATION AS A MEANS OF PREVENTION AND MANAGEMENT OF IBD. 2017 2 4281 53 MICRONUTRIENTS IN PREGNANCY IN LOW- AND MIDDLE-INCOME COUNTRIES. PREGNANCY IS ONE OF THE MORE IMPORTANT PERIODS IN LIFE WHEN INCREASED MICRONUTRIENTS, AND MACRONUTRIENTS ARE MOST NEEDED BY THE BODY; BOTH FOR THE HEALTH AND WELL-BEING OF THE MOTHER AND FOR THE GROWING FOETUS AND NEWBORN CHILD. THIS BRIEF REVIEW AIMS TO IDENTIFY THE MICRONUTRIENTS (VITAMINS AND MINERALS) LIKELY TO BE DEFICIENT IN WOMEN OF REPRODUCTIVE AGE IN LOW- AND MIDDLE-INCOME COUNTRIES (LMIC), ESPECIALLY DURING PREGNANCY, AND THE IMPACT OF SUCH DEFICIENCIES. A GLOBAL PREVALENCE OF SOME TWO BILLION PEOPLE AT RISK OF MICRONUTRIENT DEFICIENCIES, AND MULTIPLE MICRONUTRIENT DEFICIENCIES OF MANY PREGNANT WOMEN IN LMIC UNDERLINE THE URGENCY TO ESTABLISHING THE OPTIMAL RECOMMENDATIONS, INCLUDING FOR DELIVERY. IT HAS LONG BEEN RECOGNIZED THAT ADEQUATE IRON IS IMPORTANT FOR BEST REPRODUCTIVE OUTCOMES, INCLUDING GESTATIONAL COGNITIVE DEVELOPMENT. SIMILARLY, IODINE AND CALCIUM HAVE BEEN RECOGNIZED FOR THEIR ROLES IN DEVELOPMENT OF THE FOETUS/NEONATE. LESS CLEAR EFFECTS OF DEFICIENCIES OF ZINC, COPPER, MAGNESIUM AND SELENIUM HAVE BEEN REPORTED. FOLATE SUFFICIENCY PERICONCEPTIONALLY IS RECOGNIZED BOTH BY THE PRACTICE OF PROVIDING FOLIC ACID IN ANTENATAL IRON/FOLIC ACID SUPPLEMENTATION AND BY INCREASING NUMBERS OF COUNTRIES FORTIFYING FLOURS WITH FOLIC ACID. OTHER VITAMINS LIKELY TO BE IMPORTANT INCLUDE VITAMINS B12, D AND A WITH THE WATER-SOLUBLE VITAMINS GENERALLY LESS LIKELY TO BE A PROBLEM. EPIGENETIC INFLUENCES AND THE LIKELY INFLUENCE OF MICRONUTRIENT DEFICIENCIES ON FOETAL ORIGINS OF ADULT CHRONIC DISEASES ARE CURRENTLY BEING CLARIFIED. MICRONUTRIENTS MAY HAVE OTHER MORE SUBTLE, UNRECOGNIZED EFFECTS. THE NECESSITY FOR IMPROVED DIETS AND HEALTH AND SANITATION ARE CONSISTENTLY RECOMMENDED, ALTHOUGH THESE ARE NOT ALWAYS AVAILABLE TO MANY OF THE WORLD'S PREGNANT WOMEN. CONSEQUENTLY, SUPPLEMENTATION PROGRAMMES, FORTIFICATION OF STAPLES AND CONDIMENTS, AND NUTRITION AND HEALTH SUPPORT NEED TO BE SCALED-UP, SUPPORTED BY SOCIAL AND CULTURAL MEASURES. BECAUSE OF THE LIFE-LONG INFLUENCES ON REPRODUCTIVE OUTCOMES, INCLUDING INTER-GENERATIONAL ONES, BOTH CLINICAL AND PUBLIC HEALTH MEASURES NEED TO ENSURE ADEQUATE MICRONUTRIENT INTAKES DURING PREGNANCY, BUT ALSO DURING ADOLESCENCE, THE FIRST FEW YEARS OF LIFE, AND DURING LACTATION. MANY ANTENATAL PROGRAMMES ARE NOT CURRENTLY ACHIEVING THIS. WE AIM TO ADDRESS THE NEED FOR MICRONUTRIENTS DURING PREGNANCY, THE IMPORTANCE OF MICRONUTRIENT DEFICIENCIES DURING GESTATION AND BEFORE, AND PROPOSE THE SCALING-UP OF CLINICAL AND PUBLIC HEALTH APPROACHES THAT ACHIEVE HEALTHIER PREGNANCIES AND IMPROVED PREGNANCY OUTCOMES. 2015 3 2102 34 EPIGENETIC EFFECTS OF SELENIUM AND THEIR IMPLICATIONS FOR HEALTH. ALTERATIONS OF EPIGENETIC MARKS ARE LINKED TO NORMAL DEVELOPMENT AND CELLULAR DIFFERENTIATION AS WELL AS TO THE PROGRESSION OF COMMON CHRONIC DISEASES. THE PLASTICITY OF THESE MARKS PROVIDES POTENTIAL FOR DISEASE THERAPIES AND PREVENTION STRATEGIES. MACRO- AND MICRO-NUTRIENTS HAVE BEEN SHOWN TO MODULATE DISEASE RISK IN PART VIA EFFECTS ON THE EPIGENOME. THE ESSENTIAL MICRONUTRIENT SELENIUM AFFECTS HUMAN HEALTH OUTCOMES, E.G., CANCERS, CARDIOVASCULAR AND AUTOIMMUNE DISEASES, VIA SELENOPROTEINS AND THROUGH A RANGE OF BIOLOGICALLY ACTIVE DIETARY SELENOCOMPOUNDS AND METABOLISM PRODUCTS THEREOF. THIS REVIEW PROVIDES AN ASSESSMENT OF THE CURRENT LITERATURE REGARDING EPIGENETIC EFFECTS OF DIETARY AND SYNTHETIC SELENOCOMPOUNDS, WHICH INCLUDE THE MODULATION OF MARKS AND EDITORS OF EPIGENETIC INFORMATION AND INTERFERENCE WITH ONE-CARBON METABOLISM, WHICH PROVIDES THE METHYL DONOR FOR DNA METHYLATION. THE RELEVANCE OF A SELENIUM-EPIGENOME INTERACTION FOR HUMAN HEALTH IS DISCUSSED, AND WE ALSO INDICATE WHERE FUTURE STUDIES WILL BE HELPFUL TO GAIN A DEEPER UNDERSTANDING OF EPIGENETIC EFFECTS ELICITED BY SELENIUM. 2015 4 3546 58 IMMUNOMODULATORY DIET IN PEDIATRIC AGE. IN THE LAST FEW DECADES, THE IMPORTANCE OF A FUNCTIONING IMMUNE SYSTEM AND HEALTH STATUS HAS BECOME MORE EVIDENT. MULTIPLE FACTORS ARE ABLE TO INFLUENCE THE DEVELOPMENT OF CHRONIC DISEASES AND DIET IS ONE OF THE MOST IMPORTANT ENVIRONMENTAL FACTORS. EVIDENCE DEMONSTRATES THAT DIETARY PATTERNS HIGH IN FAT AND LOW IN FIBER ARE ASSOCIATED WITH THE DEVELOPMENT OF NON-COMMUNICABLE DISEASES. MOREOVER, OPTIMAL NUTRITIONAL STATUS CAN MODULATE IMMUNE MATURATION AND RESPONSE TO INFLAMMATION. DURING INFLAMMATORY CONDITIONS, NUTRITIONAL DEFICIENCIES MAY OCCUR, ESTABLISHING A VICIOUS CIRCLE, CONSEQUENTLY A BALANCED NUTRITIONAL STATUS IS ESSENTIAL TO PREVENT AND COUNTERACT INFECTIONS. DIETARY DIVERSITY CAN PREVENT ALLERGIC DISEASES AND NUTRIENTS SUCH AS DHA, ARGININE, VITAMINS AND TRACE ELEMENTS HAVE AN IMPACT ON PHYSICAL BARRIERS (SUCH AS GUT MUCOSAL BARRIER AND SKIN), ON THE IMMUNE SYSTEM RESPONSE AND ON MICROBIOME MODULATION. PROTEIN DEFICIENCIES CAN COMPROMISE INNATE AND ADAPTIVE IMMUNE FUNCTIONS; ARGININE AVAILABILITY CAN AFFECT THE IMMUNE RESPONSE IN INJURED STATES AND OTHER DISEASE PROCESSES; EPA AND DHA CAN MODULATE BOTH INNATE AND ADAPTIVE IMMUNITY; PREBIOTICS HAVE A BENEFICIAL EFFECT ON THE FUNCTIONING OF THE IMMUNE SYSTEM. ZINC, COPPER, SELENIUM AND IRON ARE INVOLVED IN THE CORRECT DEVELOPMENT AND FUNCTION OF THE IMMUNE SYSTEM. VITAMINS D, E, A, B AND C HAVE A ROLE ON IMMUNE SYSTEM THROUGH DIFFERENT MECHANISMS OF ACTION. SINCE A COMPLEX INTERPLAY EXISTS BETWEEN DIET, MICROBIOME AND EPIGENETIC FACTORS WHICH DETERMINE NUTRIENT-INDUCED CHANGES ON THE IMMUNE FUNCTION, THE EFFECT OF EACH SINGLE NUTRIENT MAY BE DIFFICULT TO STUDY. WELL-DESIGNED INTERVENTION STUDIES, INVESTIGATING THE EFFECTS OF WHOLE DIETARY PATTERN, SHOULD BE PERFORMED TO CLARIFY IMPACT OF FOODS ON THE IMMUNE FUNCTION AND DISEASE RISK. 2021 5 617 45 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 6 1836 31 EFFECTS OF NUTRIENT AND BIOACTIVE FOOD COMPONENTS ON ALZHEIMER'S DISEASE AND EPIGENETIC. ALZHEIMER'S DISEASE (AD) IS THE MOST COMMON FORM OF DEMENTIA IN THE ELDERLY AND IS A CHRONIC NEURODEGENERATIVE DISEASE THAT IS BECOMING WIDESPREAD. FOR THIS REASON, IN RECENT YEARS FACTORS AFFECTING THE DEVELOPMENT, PROGRESSION AND COGNITIVE FUNCTION OF THE AD HAVE BEEN EMPHASIZED. NUTRIENTS AND OTHER BIOACTIVE NUTRIENTS ARE AMONG THE FACTORS THAT ARE EFFECTIVE IN AD. IN PARTICULAR, VITAMINS A, C AND E, VITAMINS B(1), B(6) AND B(12), FOLATE, MAGNESIUM, CHOLINE, INOSITOL, ANTHOCYANINS, ISOFLAVONES ETC. NUTRIENTS AND BIOACTIVE NUTRIENTS ARE KNOWN TO BE EFFECTIVE IN THE DEVELOPMENT OF AD. NUTRIENTS AND NUTRIENT COMPONENTS MAY ALSO HAVE AN EPIGENETIC EFFECT ON AD. AT THE SAME TIME, NUTRIENTS AND BIOACTIVE FOOD COMPONENTS SLOW DOWN THE PROGRESSION OF THE DISEASE. FOR THIS REASON, THE EFFECT OF NUTRIENTS AND FOOD COMPONENTS ON AD WAS EXAMINED IN THIS REVIEW. 2019 7 1939 43 EPIDEMIOLOGY AND (PATHO)PHYSIOLOGY OF FOLIC ACID SUPPLEMENT USE IN OBESE WOMEN BEFORE AND DURING PREGNANCY. PRECONCEPTION FOLIC ACID SUPPLEMENT USE IS A WELL-KNOWN METHOD OF PRIMARY PREVENTION OF NEURAL TUBE DEFECTS (NTDS). OBESE WOMEN ARE AT A HIGHER RISK FOR HAVING A CHILD WITH A NTD. AS DIFFERENT INTERNATIONAL RECOMMENDATIONS ON FOLIC ACID SUPPLEMENT USE FOR OBESE WOMEN BEFORE AND DURING PREGNANCY EXIST, THIS NARRATIVE REVIEW PROVIDES AN OVERVIEW OF EPIDEMIOLOGY OF FOLATE DEFICIENCY IN OBESE (PRE)PREGNANT WOMEN, ELABORATES ON POTENTIAL MECHANISMS UNDERLYING FOLATE DEFICIENCY, AND DISCUSSES CONSIDERATIONS FOR THE USAGE OF HIGHER DOSES OF FOLIC ACID SUPPLEMENTS. WOMEN WITH OBESITY MORE OFTEN SUFFER FROM AN ABSOLUTE FOLATE DEFICIENCY, AS THEY ARE LESS COMPLIANT TO PERICONCEPTIONAL FOLIC ACID SUPPLEMENT USE RECOMMENDATIONS. IN ADDITION, THEIR DIETARY FOLATE INTAKE IS LIMITED DUE TO AN UNBALANCED DIET (RELATIVE MALNUTRITION). THE ASSOCIATION OF OBESITY AND NTDS ALSO SEEMS TO BE INDEPENDENT OF FOLATE INTAKE, WITH STUDIES SUGGESTING AN INCREASED NEED OF FOLATE (RELATIVE DEFICIENCY) DUE TO DERANGEMENTS INVOLVED IN OTHER PATHWAYS. THE RELATIVE FOLATE DEFICIENCY, AS A RESULT OF AN INCREASED METABOLIC NEED FOR FOLATE IN OBESE WOMEN, CAN BE DUE TO: (1) LOW-GRADE CHRONIC INFLAMMATION (2) INSULIN RESISTANCE, (3) INOSITOL, AND (4) DYSBIOTIC GUT MICROBIOME, WHICH PLAYS A ROLE IN FOLATE PRODUCTION AND UPTAKE. IN ALL THESE PATHWAYS, THE FOLATE-DEPENDENT ONE-CARBON METABOLISM IS INVOLVED. IN CONCLUSION, SCIENTIFIC EVIDENCE OF THE INVOLVEMENT OF SEVERAL FOLATE-RELATED PATHWAYS IMPLIES TO INCREASE THE RECOMMENDED FOLIC ACID SUPPLEMENTATION IN OBESE WOMEN. HOWEVER, THE PHYSIOLOGICAL UPTAKE OF SYNTHETIC FOLIC ACID IS LIMITED AND SIDE-EFFECTS OF UNMETABOLIZED FOLIC ACID IN MOTHERS AND OFFSPRING, IN PARTICULAR VARIATIONS IN EPIGENETIC (RE)PROGRAMMING WITH LONG-TERM HEALTH EFFECTS, CANNOT BE EXCLUDED. THEREFORE, WE EMPHASIZE ON THE URGENT NEED FOR FURTHER RESEARCH AND PRECONCEPTION PERSONALIZED COUNSELING ON FOLATE STATUS, LIFESTYLE, AND MEDICAL CONDITIONS. 2021 8 1395 64 DIET AND MICROBIOME IN THE BEGINNING OF THE SEQUENCE OF GUT INFLAMMATION. INFLAMMATORY BOWEL DISEASE (IBD) IS A CHRONIC INFLAMMATORY CONDITION OF THE GASTROINTESTINAL TRACT DUE, AT LEAST PARTIALLY, TO AN ABERRANT AND EXCESSIVE MUCOSAL IMMUNE RESPONSE TO GUT BACTERIA IN GENETICALLY-PREDISPOSED INDIVIDUALS UNDER CERTAIN ENVIRONMENTAL FACTORS. THE INCIDENCE OF IBD IS RISING IN WESTERN AND NEWLY INDUSTRIALIZED COUNTRIES, PARALLELING THE INCREASE OF WESTERNIZED DIETARY PATTERNS, THROUGH NEW ANTIGENS, EPITHELIAL FUNCTION AND PERMEABILITY, EPIGENETIC MECHANISMS (E.G., DNA METHYLATION), AND ALTERATION OF THE GUT MICROBIOME. ALTERATION IN THE COMPOSITION AND FUNCTIONALITY OF THE GUT MICROBIOME (INCLUDING BACTERIA, VIRUSES AND FUNGI) SEEMS TO BE A NUCLEAR PATHOGENIC FACTOR. THE MICROBIOME ITSELF IS DYNAMIC, AND THE CHANGES IN FOOD QUALITY, DIETARY HABITS, LIVING CONDITIONS AND HYGIENE OF THESE WESTERN SOCIETIES, COULD INTERACT IN A COMPLEX MANNER AS MODULATORS OF DYSBIOSIS, THEREBY INFLUENCING THE ACTIVATION OF IMMUNE CELLS' PROMOTING INFLAMMATION. THE MICROBIOME PRODUCES DIVERSE SMALL MOLECULES VIA SEVERAL METABOLIC WAYS, WITH THE FIBER-DERIVED SHORT-CHAIN FATTY ACIDS (I.E., BUTYRATE) AS MAIN ELEMENTS AND HAVING ANTI-INFLAMMATORY EFFECTS. THESE METABOLITES AND SOME MICRONUTRIENTS OF THE DIET (I.E., VITAMINS, FOLIC ACID, BETA CAROTENE AND TRACE ELEMENTS) ARE REGULATORS OF INNATE AND ADAPTIVE INTESTINAL IMMUNE HOMEOSTASIS. AN EXCESSIVE AND UNHEALTHY CONSUMPTION OF SUGAR, ANIMAL FAT AND A LOW-VEGETABLE AND -FIBER DIET ARE RISK FACTORS FOR IBD APPEARANCE. FURTHERMORE, METABOLISM OF NUTRIENTS IN INTESTINAL EPITHELIUM AND IN GUT MICROBIOTA IS ALTERED BY INFLAMMATION, CHANGING THE DEMAND FOR NUTRIENTS NEEDED FOR HOMEOSTASIS. THIS ROLE OF FOOD AND A REDUCED GUT MICROBIAL DIVERSITY IN CAUSING IBD MIGHT ALSO HAVE A PROPHYLACTIC OR THERAPEUTIC ROLE FOR IBD. THE RELATIONSHIP BETWEEN DIETARY INTAKE, SYMPTOMS, AND BOWEL INFLAMMATION COULD LEAD TO DIETARY AND LIFESTYLE RECOMMENDATIONS, INCLUDING DIETS WITH ABUNDANT FRUITS, VEGETABLES, OLIVE OIL AND OILY FISH, WHICH HAVE ANTI-INFLAMMATORY EFFECTS AND COULD PREVENT DYSBIOSIS AND IBD. DIETARY MODULATION AND APPROPRIATE EXCLUSION DIETS MIGHT BE A NEW COMPLEMENTARY MANAGEMENT FOR TREATMENT AT DISEASE FLARES AND IN REFRACTORY PATIENTS, EVEN REDUCING COMPLICATIONS, HOSPITALIZATIONS AND SURGERY, THROUGH MODIFYING THE LUMINAL INTESTINAL ENVIRONMENT. 2021 9 4796 50 NUTRITIONAL INTERVENTION AS AN ESSENTIAL PART OF MULTIPLE SCLEROSIS TREATMENT? MULTIPLE SCLEROSIS (MS) IS A CHRONIC INFLAMMATORY AND DEMYELINATING DISEASE OF THE CENTRAL NERVOUS SYSTEM. IN ADDITION TO THE GENETIC, EPIGENETIC AND IMMUNOLOGICAL COMPONENTS, VARIOUS OTHER FACTORS, E.G. UNHEALTHY DIETARY HABITS, PLAY A ROLE IN THE MS PATHOGENESIS. DIETARY INTERVENTION IS A HIGHLY APPEALING APPROACH, AS IT PRESENTS A SIMPLE AND RELATIVELY LOW RISK METHOD TO POTENTIALLY IMPROVE OUTCOMES IN PATIENTS WITH BRAIN DISORDERS IN ORDER TO ACHIEVE REMISSION AND IMPROVEMENT OF CLINICAL STATUS, WELL-BEING AND LIFE EXPECTANCY OF PATIENTS WITH MS. THE IMPORTANCE OF SATURATED FAT INTAKE RESTRICTION FOR THE CLINICAL STATUS IMPROVEMENT OF MS PATIENTS WAS POINTED FOR THE FIRST TIME IN 1950S. RECENTLY, DECREASED RISK OF FIRST CLINICAL DIAGNOSIS OF CNS DEMYELINATION ASSOCIATED WITH HIGHER INTAKE OF OMEGA-3 POLYUNSATURATED FATTY ACIDS PARTICULARLY ORIGINATING FROM FISH WAS REPORTED. ONLY FEW CLINICAL TRIALS HAVE BEEN PERFORMED TO ADDRESS THE QUESTION OF THE ROLE OF DIETARY INTERVENTION, SUCH IS E.G. LOW SATURATED FAT DIET IN MS TREATMENT. THIS REVIEW SUMMARIZES CURRENT KNOWLEDGE ABOUT THE EFFECT OF DIFFERENT DIETARY APPROACHES (DIETS LOW IN SATURATED FAT AND DIETARY SUPPLEMENTS SUCH AS FISH OIL, LIPOIC ACID, OMEGA-3 POLYUNSATURATED FATTY ACIDS, SEEDS OILS, HIGH FIBER DIET, VITAMIN D, ETC.) ON NEUROLOGICAL SIGNS, PATIENT'S WELL-BEING, PHYSICAL AND INFLAMMATORY STATUS. SO FAR THE RESULTS ARE NOT CONCLUSIVE, THEREFORE MUCH MORE RESEARCH IS NEEDED TO CONFIRM AND TO UNDERSTAND THE EFFECTIVENESS OF THESE DIETARY INTERVENTIONS IN THE LONG TERM AND WELL DEFINED STUDIES. 2018 10 1710 36 DYSFUNCTIONAL IMMUNOMETABOLIC EFFECTS OF VITAMIN D DEFICIENCY, INCREASED CARDIOMETABOLIC RISK. POTENTIAL EPIDEMIOLOGICAL ALERT IN AMERICA? VITAMIN D DEFICIENCY IS A SERIOUS PUBLIC HEALTH PROBLEM WORLDWIDE THAT AFFECTS NOT ONLY SKELETAL HEALTH, BUT ALSO A WIDE RANGE OF ACUTE AND CHRONIC DISEASES. HOWEVER, THERE IS STILL SKEPTICISM BECAUSE OF THE LACK OF RANDOMIZED, CONTROLLED TRIALS TO SUPPORT ASSOCIATION STUDIES ON THE BENEFITS OF VITAMIN D FOR NON-SKELETAL HEALTH. THIS REVIEW WAS BASED ON ARTICLES PUBLISHED DURING THE 1980-2015 OBTAINED FROM THE COCHRANE CENTRAL REGISTER OF CONTROLLED TRIALS, MEDLINE AND PUBMED, AND FOCUSES ON RECENT CHALLENGES WITH REGARD TO THE DEFINITION OF VITAMIN D DEFICIENCY AND HOW TO ACHIEVE OPTIMAL SERUM 25-HYDROXYVITAMIN D LEVELS FROM DIETARY SOURCES, SUPPLEMENTS, AND SUN EXPOSURE. THE EFFECT OF VITAMIN D ON EPIGENETIC FETAL PROGRAMMING AND REGULATION OF GENES THAT MAY POTENTIALLY EXPLAIN WHY VITAMIN D COULD HAVE SUCH LIFELONG COMPREHENSIVE HEALTH BENEFITS IS REVIEWED. OPTIMIZATION OF VITAMIN D LEVELS IN CHILDREN AND ADULTS AROUND THE WORLD HAS POTENTIAL BENEFITS TO IMPROVE SKELETAL HEALTH AND TO REDUCE THE RISK OF CHRONIC DISEASES, INCLUDING SOME TYPES OF CANCER, AUTOIMMUNE DISEASES, INFECTIOUS DISEASES, TYPE 2 DIABETES MELLITUS, AND SEVERE CARDIOVASCULAR DISORDERS SUCH AS ATHEROTHROMBOSIS, NEUROCOGNITIVE DISORDERS, AND MORTALITY. 2017 11 4080 30 MATERNAL LIFESTYLE INTERVENTIONS: TARGETING PRECONCEPTION HEALTH. ABOUT ONE-THIRD OF WOMEN OF REPRODUCTIVE AGE ARE OBESE, PREDISPOSING BOTH MOTHER AND BABY TO UNFAVOURABLE PREGNANCY OUTCOMES AND INITIATING AN INTERGENERATIONAL CYCLE OF CHRONIC METABOLIC DISORDERS. HERE WE SUMMARISE RECENT RESEARCH ON THE INFLUENCE OF MATERNAL METABOLIC HEALTH ON OFFSPRING SUSCEPTIBILITY TO FUTURE CARDIOMETABOLIC DISEASES. CURRENT PRIMARY LIFESTYLE APPROACHES (I.E., DIET AND EXERCISE INTERVENTIONS) TO HALT THE SUCCESSION OF INHERITED AND EPIGENETIC METABOLIC ABNORMALITIES HAVE MET WITH LIMITED SUCCESS DUE TO LATE IMPLEMENTATION, POOR ADHERENCE, AND/OR GENERIC GUIDELINES. IN OUR OPINION, SUCH INTERVENTIONS MUST COMMENCE PRIOR TO CONCEPTION TO IMPROVE BOTH MATERNAL AND CHILD HEALTH OUTCOMES, WITH NEW APPROACHES URGENTLY NEEDED TO INCREASE ADHERENCE TO PRIMARY LIFESTYLE CHANGES AMONG REPRODUCTIVE-AGE WOMEN. 2020 12 4786 42 NUTRITION AND HEALTH DURING MID-LIFE: SEARCHING FOR SOLUTIONS AND MEETING CHALLENGES FOR THE AGING POPULATION. INTERACTIONS BETWEEN GENETIC (GENOME) AND ENVIRONMENTAL FACTORS (EPIGENOME) OPERATE DURING A PERSON'S ENTIRE LIFESPAN. THE AGING PROCESS IS ASSOCIATED WITH SEVERAL CELLULAR AND ORGANIC FUNCTIONAL ALTERATIONS THAT, AT THE END, CAUSE MULTI-ORGANIC CELL FAILURE. EPIGENETIC MECHANISMS OF AGING ARE MODIFIABLE BY APPROPRIATE PREVENTIVE ACTIONS MEDIATED BY SIRTUINS, CALORIC INPUT, DIET COMPONENTS, ADIPOSE TISSUE-RELATED INFLAMMATORY REACTIONS, AND PHYSICAL ACTIVITY. THE MEDITERRANEAN LIFESTYLE HAS BEEN FOR MANY MILLENNIA A DAILY HABIT FOR PEOPLE IN WESTERN CIVILIZATIONS LIVING AROUND THE MEDITERRANEAN SEA WHO WORKED INTENSIVELY AND SURVIVED WITH VERY FEW SEASONAL FOODS. A HIGH ADHERENCE TO THE TRADITIONAL MEDITERRANEAN DIET IS ASSOCIATED WITH LOW MORTALITY (HIGHER LONGEVITY) AND REDUCED RISK OF DEVELOPING CHRONIC DISEASES, INCLUDING CANCER, THE METABOLIC SYNDROME, DEPRESSION AND CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES. REPORTS INDICATE THAT SOME DIETARY COMPONENTS, SUCH AS OLIVE OIL, ANTIOXIDANTS, OMEGA-3 AND -6 POLYUNSATURATED ACIDS, POLYPHENOLS AND FLAVONOIDS, MEDIATE BENEFICIAL ANTI-AGING EFFECTS (ANTI-CHRONIC DISEASES AND INCREASED LONGEVITY). EQUALLY, PHYSICAL ACTIVITY DISPLAYS A POSITIVE EFFECT, PRODUCING CALORIC CONSUMPTION AND REGULATION OF ADIPOSE AND PANCREATIC FUNCTION. THE PREDICTIVE STRENGTH OF SOME FOOD PATTERNS MAY BE A WAY OF DEVELOPING RECOMMENDATIONS FOR FOOD AND HEALTH POLICIES. THIS PAPER WILL DISCUSS SEVERAL WAYS OF IMPROVING HEALTH DURING MID-LIFE, FOCUSING ON CERTAIN GROUPS OF FUNCTIONAL FOODS AND HEALTHY HABITS WHICH MAY REDUCE OR PREVENT AGE-RELATED CHRONIC DISEASES. 2013 13 2869 49 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 14 6169 30 THE GUT MICROBIOTA AND HEALTHY AGING: A MINI-REVIEW. THE GUT MICROBIOTA SHOWS A WIDE INTER-INDIVIDUAL VARIATION, BUT ITS WITHIN-INDIVIDUAL VARIATION IS RELATIVELY STABLE OVER TIME. A FUNCTIONAL CORE MICROBIOME, PROVIDED BY ABUNDANT BACTERIAL TAXA, SEEMS TO BE COMMON TO VARIOUS HUMAN HOSTS REGARDLESS OF THEIR GENDER, GEOGRAPHIC LOCATION, AND AGE. WITH ADVANCING CHRONOLOGICAL AGE, THE GUT MICROBIOTA BECOMES MORE DIVERSE AND VARIABLE. HOWEVER, WHEN MEASURES OF BIOLOGICAL AGE ARE USED WITH ADJUSTMENT FOR CHRONOLOGICAL AGE, OVERALL RICHNESS DECREASES, WHILE A CERTAIN GROUP OF BACTERIA ASSOCIATED WITH FRAILTY INCREASES. THIS HIGHLIGHTS THE IMPORTANCE OF CONSIDERING BIOLOGICAL OR FUNCTIONAL MEASURES OF AGING. STUDIES USING MODEL ORGANISMS INDICATE THAT AGE-RELATED GUT DYSBIOSIS MAY CONTRIBUTE TO UNHEALTHY AGING AND REDUCED LONGEVITY. THE GUT MICROBIOME DEPENDS ON THE HOST NUTRIENT SIGNALING PATHWAYS FOR ITS BENEFICIAL EFFECTS ON HOST HEALTH AND LIFESPAN, AND GUT DYSBIOSIS DISRUPTING THE INTERDEPENDENCE MAY DIMINISH THE BENEFICIAL EFFECTS OR EVEN HAVE REVERSE EFFECTS. GUT DYSBIOSIS CAN TRIGGER THE INNATE IMMUNE RESPONSE AND CHRONIC LOW-GRADE INFLAMMATION, LEADING TO MANY AGE-RELATED DEGENERATIVE PATHOLOGIES AND UNHEALTHY AGING. THE GUT MICROBIOTA COMMUNICATES WITH THE HOST THROUGH VARIOUS BIOMOLECULES, NUTRIENT SIGNALING-INDEPENDENT PATHWAYS, AND EPIGENETIC MECHANISMS. DISTURBANCE OF THESE COMMUNICATIONS BY AGE-RELATED GUT DYSBIOSIS CAN AFFECT THE HOST HEALTH AND LIFESPAN. THIS MAY EXPLAIN THE IMPACT OF THE GUT MICROBIOME ON HEALTH AND AGING. 2018 15 6724 41 VITAMIN D: EFFECTS ON PREGNANCY, MATERNAL, FETAL AND POSTNATAL OUTCOMES. A HIGH PREVALENCE OF VITAMIN D DEFICIENCY AND ITS NEGATIVE CONSEQUENCES FOR HEALTH IS IDENTIFIED AS AREA OF PRIMARY CONCERN FOR SCIENTISTS AND CLINICIANS WORLDWIDE. VITAMIN D DEFICIENCY AFFECTS NOT ONLY BONE HEALTH BUT MANY SOCIALLY SIGNIFICANT ACUTE AND CHRONIC DISEASES. OBSERVATIONAL STUDIES SUPPORT THAT PREGNANT AND LACTATING WOMEN, CHILDREN AND TEENAGERS REPRESENT THE HIGH RISK GROUPS FOR DEVELOPING VITAMIN D DEFICIENCY. CURRENT EVIDENCE HIGHLIGHTS A CRUCIAL ROLE OF VITAMIN D IN PROVIDING THE FETAL LIFE-SUPPORT SYSTEM AND FETUS DEVELOPMENT, INCLUDING IMPLANTATION, PLACENTAL FORMATION, INTRA- AND POSTPARTUM PERIODS. HYPOVITAMINOSIS D DURING PREGNANCY IS ASSOCIATED WITH A HIGHER INCIDENCE OF PLACENTAL INSUFFICIENCY, SPONTANEOUS ABORTIONS AND PRETERM BIRTH, PREECLAMPSIA, GESTATIONAL DIABETES, IMPAIRED FETAL AND CHILDHOOD GROWTH, INCREASED RISK OF AUTOIMMUNE DISEASES FOR OFFSPRINGS. POTENTIAL MECHANISMS FOR THE OBSERVED ASSOCIATIONS CONTAIN METABOLIC, IMMUNOMODULATORY AND ANTIINFLAMMATORY EFFECTS OF VITAMIN D. EPIGENETIC MODIFICATIONS IN VITAMIN D-ASSOCIATED GENES AND FETAL PROGRAMMING ARE OF PARTICULAR INTEREST. THE CONCEPT OF PREVENTING VITAMIN D DEFICIENCY IS ACTIVELY DISCUSSED, INCLUDING SUPPLEMENTATION IN DIFFERENT ETHNIC GROUPS, REQUIRED DOSES, TIME OF INITIATION AND THERAPY DURATION, INFLUENCE ON GESTATION AND CHILDBIRTH. AN ADEQUATE SUPPLY OF VITAMIN D DURING PREGNANCY IMPROVES THE MATERNAL AND FETAL OUTCOMES, SHORT AND LONG TERM HEALTH OF THE OFFSPRING. STILL CURRENT DATA ON RELATIONSHIP BETWEEN MATERNAL VITAMIN D STATUS AND PREGNANCY OUTCOMES REMAINS CONTROVERSIAL. THE LARGE OBSERVATIONAL AND INTERVENTIONAL RANDOMIZED CONTROL TRIALS ARE REQUIRED TO CREATE EVIDENCE-BASED GUIDELINES FOR THE SUPPLEMENTATION OF VITAMIN D IN PREGNANT AND LACTATING WOMEN. 2018 16 5089 40 PLACENTAL ADAPTATIONS TO MICRONUTRIENT DYSREGULATION IN THE PROGRAMMING OF CHRONIC DISEASE. POOR NUTRITION DURING PREGNANCY IS KNOWN TO IMPAIR FOETAL DEVELOPMENT AND INCREASE THE RISK OF CHRONIC DISEASE IN OFFSPRING. BOTH MACRONUTRIENTS AND MICRONUTRIENTS ARE REQUIRED FOR A HEALTHY PREGNANCY ALTHOUGH SIGNIFICANTLY LESS IS UNDERSTOOD ABOUT THE ROLE OF MICRONUTRIENTS IN THE PROGRAMMING OF CHRONIC DISEASE. THIS IS DESPITE THE FACT THAT MODERN CALORIE RICH DIETS ARE OFTEN ALSO DEFICIENT IN KEY MICRONUTRIENTS. THE IMPORTANCE OF MICRONUTRIENTS IN GESTATIONAL DISORDERS IS CLEARLY UNDERSTOOD BUT HOW THEY IMPACT LONG TERM DISEASE IN HUMANS REQUIRES FURTHER INVESTIGATION. IN CONTRAST, ANIMAL STUDIES HAVE DEMONSTRATED HOW DIETS HIGH OR LOW IN SPECIFIC MICRONUTRIENTS INFLUENCE OFFSPRING PHYSIOLOGY. MANY OF THESE STUDIES HIGHLIGHT THE IMPORTANCE OF THE PLACENTA IN DETERMINING DISEASE RISK. THIS REVIEW WILL EXPLORE THE EFFECTS OF INDIVIDUAL VITAMINS, MINERALS AND TRACE ELEMENTS ON OFFSPRING DISEASE OUTCOMES AND DISCUSS SEVERAL KEY PLACENTAL ADAPTATIONS THAT ARE AFFECTED BY MULTIPLE MICRONUTRIENTS. THESE PLACENTAL ADAPTATIONS INCLUDE MICRONUTRIENT INDUCED DYSREGULATION OF OXIDATIVE STRESS, ALTERED METHYL DONOR AVAILABILITY AND ITS IMPACT ON EPIGENETIC MECHANISMS AS WELL AS ENDOCRINE DYSFUNCTION. CRITICAL GAPS IN OUR CURRENT KNOWLEDGE AND THE RELATIVE IMPORTANCE OF DIFFERENT MICRONUTRIENTS AT DIFFERENT GESTATIONAL AGES WILL ALSO BE HIGHLIGHTED. FINALLY, THIS REVIEW WILL DISCUSS THE NEED FOR FURTHER STUDIES TO CHARACTERISE THE MICRONUTRIENT STATUS OF AUSTRALIAN WOMEN OF REPRODUCTIVE AGE AND CORRELATE MICRONUTRIENT STATUS TO PLACENTAL ADAPTATIONS, PREGNANCY COMPLICATIONS AND OFFSPRING DISEASE. 2018 17 1417 37 DIETARY TRENDS AND THE DECLINE IN MALE REPRODUCTIVE HEALTH. OVER THE TWENTIETH CENTURY, MALE REPRODUCTIVE HEALTH HAS SUFFERED A SUBSTANTIAL DECLINE, AS EVIDENCED BY DECREASES IN SPERM COUNTS AND TESTOSTERONE LEVELS AND INCREASES IN REPRODUCTIVE PATHOLOGIES. AT THE SAME TIME, THE PREVALENCE OF CHRONIC DISEASES SUCH AS OBESITY, DIABETES, AND METABOLIC SYNDROME HAS RISEN DRAMATICALLY. METABOLIC AND REPRODUCTIVE HEALTH ARE HIGHLY INTERCONNECTED, SUGGESTING THAT THEIR RESPECTIVE TRENDS ARE INTERTWINED AND, GIVEN THE TIMEFRAME OF SUCH TRENDS, ENVIRONMENTAL AND NOT GENETIC FACTORS ARE MOST LIKELY TO BE THE PRIMARY CAUSES. INDUSTRIALIZATION, WHICH BEGAN IN EUROPE IN THE MID-EIGHTEENTH CENTURY, HAS RESULTED IN PROFOUND CHANGES TO OUR DIET, LIFESTYLE, AND ENVIRONMENT, MANY OF WHICH ARE CAUSAL FACTORS IN THE RISE IN CHRONIC DISEASES. INDUSTRIALIZATION RESULTS IN A NUTRITION TRANSITION FROM AN AGRICULTURAL UNPROCESSED TO A MODERN PROCESSED DIET, INCORPORATING INCREASES IN SUGAR, VEGETABLE OILS, ULTRA-PROCESSED FOODS, LINOLEIC ACID, TRANS-FATS, AND TOTAL ENERGY. THIS DIETARY SHIFT HAS INCURRED NUMEROUS ADVERSE EFFECTS ON METABOLIC AND REPRODUCTIVE HEALTH, CHARACTERIZED BY CHRONIC INFLAMMATION, OXIDATIVE STRESS, AND INSULIN RESISTANCE. MOREOVER, THESE EFFECTS APPEAR TO MULTIPLY ACROSS SUBSEQUENT GENERATIONS VIA EPIGENETIC INHERITANCE. MEN'S FERTILITY IS MARKEDLY AFFECTED BY OBESITY AND DIABETES, WITH AN INCREASE IN TOTAL ENERGY VIA PROCESSED FOOD INTAKE ARGUABLY BEING THE KEY FACTOR DRIVING THE DIABESITY PANDEMIC. IN CONTRAST, WHOLEFOODS RICH IN MICRONUTRIENTS AND PHYTONUTRIENTS SUPPORT MALE FERTILITY AND A HEALTHY BODY WEIGHT. THEREFORE, MEN WANTING TO MAXIMIZE THEIR FERTILITY SHOULD CONSIDER MAKING POSITIVE DIETARY CHANGES, SUCH AS REPLACING PROCESSED FOODS WITH UNPROCESSED FOODS THAT SUPPORT METABOLIC AND REPRODUCTIVE HEALTH. 2023 18 6305 46 THE QUESTION IS WHETHER INTAKE OF FOLIC ACID FROM DIET ALONE DURING PREGNANCY IS SUFFICIENT. PREGNANCY AND FOLIC ACID: PREGNANCY IS THE MOST IMPORTANT PERIOD IN LIFE OF EVERY WOMAN, PARTIALLY FOR THE NUMBER OF PHYSIOLOGICAL ADAPTATIONS SHE IS GOING THROUGH, PARTIALLY FOR THE EXPECTANCE OF NEW LIFE. IN ADDITION, PREGNANCY IS THE "CRITICAL WINDOW" FOR DEVELOPMENT LATER IN CHILDHOOD, AS A PERIOD OF FOETAL PROGRAMMING DURING WHICH NUTRITION PLAYS ONE OF CRUCIAL ROLES. DESPITE THE GENERAL BELIEF THAT NUTRITION THROUGH PREGNANCY IS ADEQUATE AND CHARACTERIZED BY BETTER NUTRITIONAL HABITS, A NUMBER OF STUDIES DO NOT CORROBORATE THIS BELIEF. ROLE OF FOLIC ACID: AN ADEQUATE FOLATE BLOOD LEVEL IS NECESSARY FOR NORMAL CELL GROWTH, SYNTHESIS OF SEVERAL COMPOUNDS INCLUDING DEOXYRIBONUCLEIC ACID AND RIBONUCLEIC ACID, PROPER BRAIN AND NEUROLOGIC FUNCTIONS; IT IS INCLUDED IN THE REGULATION OF HOMOCYSTEINE LEVEL, AND CLOSELY RELATED TO THE VITAMIN B12 METABOLISM. FOLATE DEFICIENCY IN PREGNANCY IS RELATED TO NEURAL TUBE DEFECTS, OTHER NEUROLOGICAL DISORDERS, PRETERM DELIVERY AND LOW BIRTH WEIGHT. FOOD SOURCES: A CORRELATION BETWEEN FOLATE AND THE PREVENTION OF BROAD SPECTRUM OF CHRONIC DISEASES HAS BEEN CONFIRMED. EMERGING EVIDENCE FROM THE EPIGENETIC STUDIES IS NOW BRINGING EVEN MORE LIGHT ON THE LEVEL OF SIGNIFICANCE OF FOLIC ACID. A WIDE RANGE OF PLANT AND ANIMAL FOODS ARE THE NATURAL SOURCES OF FOLATE; LIVER, YEAST, MUSHROOMS, AND GREEN LEAFY VEGETABLES BEING THE MOST SIGNIFICANT. DIFFERENT WAYS OF FOOD PREPARATION INFLUENCE THE FOLATE STABILITY AND ITS BIOAVAILABILITY VARIES FROM 25 TO 50% FROM FOODS, 85% FROM ENRICHED FOODS OR 100% FROM SUPPLEMENTS. CONCLUSION: A GREAT AMOUNT OF SCIENTIFIC RESULTS HAS LED TO OFFICIAL RECOMMENDATIONS FOR FOLIC ACID SUPPLEMENTATION IN PREGNANT WOMEN AS WELL AS IN A NUMBER OF OBLIGATORY OR VOLUNTARY FORTIFICATION PROGRAMMES IN ORDER TO PREVENT THE FOLATE DEFICIENCY ON THE LEVEL OF DIFFERENT POPULATION GROUPS. NEVERTHELESS, THERE MUST BE A CERTAIN LEVEL OF PRECAUTION FOR ELDERLY BECAUSE FOLATE CAN MASK THE VITAMIN B12 DEFICIENCY WITH POSSIBLE FATAL OUTCOMES. 2014 19 6290 37 THE POTENTIAL ROLE OF NUTRITIONAL GENOMICS TOOLS IN VALIDATING HIGH HEALTH FOODS FOR CANCER CONTROL: BROCCOLI AS EXAMPLE. NUTRITIONAL GENOMICS REFLECTS GENE/NUTRIENT INTERACTIONS, UTILISING HIGH-THROUGHPUT GENOMIC TOOLS IN NUTRITION RESEARCH. THE FIELD ALSO CONSIDERS THE CONTRIBUTION OF INDIVIDUAL GENOTYPES TO WELLNESS AND THE RISK OF CHRONIC DISEASE (NUTRIGENETICS), AND HOW SUCH GENETIC PREDISPOSITION MAY BE MODIFIED BY APPROPRIATE DIETS. FOR EXAMPLE, HIGH CONSUMPTION OF BRASSICACEOUS VEGETABLES, INCLUDING BROCCOLI, HAS REGULARLY ASSOCIATED WITH LOW CANCER RISK. BIOACTIVE CHEMICALS IN BROCCOLI INCLUDE GLUCOSINOLATES, PLANT PIGMENTS INCLUDING KAEMPFEROL, QUERCETIN, LUTEIN AND CAROTENOIDS, VARIOUS VITAMINS, MINERALS AND AMINO ACIDS. CANCER PREVENTION IS HYPOTHESISED TO ACT THROUGH VARIOUS MECHANISMS INCLUDING MODULATION OF XENOBIOTIC METABOLISING ENZYMES, NF-E2 P45-RELATED FACTOR-2 (NRF2)-MEDIATED STRESS-RESPONSE MECHANISMS, AND PROTECTION AGAINST GENOMIC INSTABILITY. BROCCOLI AND BROCCOLI EXTRACTS ALSO REGULATE THE PROGRESSION OF CANCER THROUGH ANTI-INFLAMMATORY EFFECTS, EFFECTS ON SIGNAL TRANSDUCTION, EPIGENETIC EFFECTS AND MODULATION OF THE COLONIC MICROFLORA. HUMAN INTERVENTION STUDIES WITH BROCCOLI AND RELATED FOODS, USING STANDARD BIOMARKER METHODOLOGIES, REVEAL PART OF A COMPLEX PICTURE. NUTRIGENOMIC APPROACHES, ESPECIALLY TRANSCRIPTOMICS, ENABLE SIMULTANEOUS STUDY OF VARIOUS SIGNALLING PATHWAYS AND NETWORKS. PHENOTYPIC, GENETIC AND/OR METABOLIC STRATIFICATION MAY IDENTIFY INDIVIDUALS MOST LIKELY TO RESPOND POSITIVELY TO FOODS OR DIETS. JOINTLY, THESE TECHNOLOGIES CAN PROVIDE PROOF OF HUMAN EFFICACY, AND MAY BE ESSENTIAL TO ENSURE EFFECTIVE MARKET TRANSFER AND UPTAKE OF BROCCOLI AND RELATED FOODS. 2012 20 4062 39 MATERNAL AND CHILD HEALTH SERVICES AND AN INTEGRATED, LIFE-CYCLE APPROACH TO THE PREVENTION OF NON-COMMUNICABLE DISEASES. DESCRIBED AS THE 'INVISIBLE EPIDEMIC', NON-COMMUNICABLE DISEASES (NCDS) ARE THE WORLD'S LEADING CAUSE OF DEATH. MOST ARE CAUSED BY PREVENTABLE FACTORS, INCLUDING POOR DIET, TOBACCO USE, HARMFUL USE OF ALCOHOL AND PHYSICAL INACTIVITY. DIABETES, CANCER AND CARDIOVASCULAR AND CHRONIC LUNG DISEASES WERE RESPONSIBLE FOR 38 MILLION (68%) OF GLOBAL DEATHS IN 2012. SINCE 1990, PROPORTIONATE NCD MORTALITY HAS INCREASED SUBSTANTIALLY AS POPULATIONS HAVE AGED AND COMMUNICABLE DISEASES DECLINE. THE MAJORITY OF NCD DEATHS, ESPECIALLY PREMATURE NCD DEATHS (<70 YEARS, 82%), OCCUR IN LOW-INCOME AND MIDDLE-INCOME COUNTRIES, AND AMONG POOR COMMUNITIES WITHIN THEM. ADDRESSING NCDS IS RECOGNISED AS CENTRAL TO THE POST-2015 AGENDA; ACCORDINGLY, NCDS HAVE A SPECIFIC OBJECTIVE AND TARGET IN THE SUSTAINABLE DEVELOPMENT GOALS. WHILE DEATHS FROM NCDS OCCUR MAINLY IN ADULTHOOD, MANY HAVE THEIR ORIGINS IN EARLY LIFE, INCLUDING THROUGH EPIGENETIC MECHANISMS OPERATING BEFORE CONCEPTION. GOOD NUTRITION BEFORE CONCEPTION AND INTERVENTIONS AIMED AT PREVENTING NCDS DURING THE FIRST 1000 DAYS (FROM CONCEPTION TO AGE 2 YEARS), CHILDHOOD AND ADOLESCENCE MAY BE MORE COST-EFFECTIVE THAN MANAGING ESTABLISHED NCDS IN LATER LIFE WITH COSTLY TESTS AND DRUGS. FOLLOWING A LIFE-COURSE APPROACH, MATERNAL AND CHILD HEALTH INTERVENTIONS, BEFORE DELIVERY AND DURING CHILDHOOD AND ADOLESCENCE, CAN PREVENT NCDS AND SHOULD INFLUENCE GLOBAL HEALTH AND SOCIOECONOMIC DEVELOPMENT. THIS PAPER DESCRIBES HOW SUCH AN APPROACH MAY BE PURSUED, INCLUDING THROUGH THE ENGAGEMENT OF NON-HEALTH SECTORS. IT ALSO EMPHASISES EVALUATING AND DOCUMENTING RELATED INITIATIVES TO UNDERWRITE SYSTEMATIC AND EVIDENCE-BASED CROSS-SECTORAL ENGAGEMENT ON NCD PREVENTION IN THE FUTURE. 2017