The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation.

Worldwide stroke is the second leading cause of death and the third leading cause of death and disability combined. The estimated global economic burden by stroke is over US$891 billion per year. Within three decades (1990-2019), the incidence increased by 70%, deaths by 43%, prevalence by 102%, and DALYs by 143%. Of over 100 million people affected by stroke, about 76% are ischemic stroke (IS) patients recorded worldwide. Contextually, ischemic stroke moves into particular focus of multi-professional groups including researchers, healthcare industry, economists, and policy-makers. Risk factors of ischemic stroke demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) and secondary (clinically manifested collateral disorders contributing to stroke risks) care. These risks are interrelated. For example, sedentary lifestyle and toxic environment both cause mitochondrial stress, systemic low-grade inflammation and accelerated ageing; inflammageing is a low-grade inflammation associated with accelerated ageing and poor stroke outcomes. Stress overload, decreased mitochondrial bioenergetics and hypomagnesaemia are associated with systemic vasospasm and ischemic lesions in heart and brain of all age groups including teenagers. Imbalanced dietary patterns poor in folate but rich in red and processed meat, refined grains, and sugary beverages are associated with hyperhomocysteinaemia, systemic inflammation, small vessel disease, and increased IS risks. Ongoing 3PM research towards vulnerable groups in the population promoted by the European Association for Predictive, Preventive and Personalised Medicine (EPMA) demonstrates promising results for the holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as a vital biosensor and AI-based multi-professional data interpretation as reported here by the EPMA expert group. Collected data demonstrate that IS-relevant risks and corresponding molecular pathways are interrelated. For examples, there is an evident overlap between molecular patterns involved in IS and diabetic retinopathy as an early indicator of IS risk in diabetic patients. Just to exemplify some of them such as the 5-aminolevulinic acid/pathway, which are also characteristic for an altered mitophagy patterns, insomnia, stress regulation and modulation of microbiota-gut-brain crosstalk. Further, ceramides are considered mediators of oxidative stress and inflammation in cardiometabolic disease, negatively affecting mitochondrial respiratory chain function and fission/fusion activity, altered sleep-wake behaviour, vascular stiffness and remodelling. Xanthine/pathway regulation is involved in mitochondrial homeostasis and stress-driven anxiety-like behaviour as well as molecular mechanisms of arterial stiffness. In order to assess individual health risks, an application of machine learning (AI tool) is essential for an accurate data interpretation performed by the multiparametric analysis. Aspects presented in the paper include the needs of young populations and elderly, personalised risk assessment in primary and secondary care, cost-efficacy, application of innovative technologies and screening programmes, advanced education measures for professionals and general population-all are essential pillars for the paradigm change from reactive medical services to 3PM in the overall IS management promoted by the EPMA.

Women's higher risk with N-6 PUFA vs. men's relative advantage: an "N-6 gender nutrition paradox" hypothesis.

The "Israeli Paradox" (1996) of low national health rankings despite adequate diet - attributed to high dietary n-6 polyunsaturated fatty acids (PUFA) - coincided with long-observed dichotomies between women's worse international status vs. men's advantage. This raised the possibility of a gender link to high n-6 risk potentially explaining both national phenomena. Israeli women's disadvantage was shown by worse international rankings, i.e., life expectancy (LE)--11th vs. men's 3rd-best/22 countries (2000), and 14th vs. 6th/34 (2010); and all-cause and all-cancer mortality--both 15th vs. 2nd-best/22 (2000), and 15th vs. 6th/22 and 12th vs. 2nd-best/22 (2010). Cancer mortality rates for breast were 21.8% above vs. prostate 30.4% below Eur-A (27 country) averages (2005). Gender gaps/ ratios were smaller than European Union-15 averages, i.e., for LE at birth by 34.4-26.4% (2000-2010), respectively, and at 65 years 45.9-35.3%; all-cause mortality by 43.3-33.4%, and all-cancer 65.2-58.7%. The Israeli diet was mostly close to guidelines, but n-6 intake (10-12% kcal) was much higher than recommended and traditional "Mediterranean diet" levels. Research showing females' greater potential for conversion of PUFA to long-chain PUFA (LCPUFA) may suggest increased production of n-6 eicosanoids with known proinflammatory/oxidative/carcinogenic potential. An "Israeli N-6 Gender Nutrition Paradox" hypothesis is suggested here for the first time, associating women's higher risk and lead in the national "paradox" with greater potential for n-6 conversion to pro-inflammatory/oxidative/carcinogenic eicosanoids compared to men. This may also exacerbate women's risk associated with genetic predisposition (i.e., BRCA) and/or sociopolitical stress. Global abandonment of traditional diets/foods together with increasing n-6 consumption and western disease rates emphasize the importance of considering gender nutrition in epidemiology and preventive strategies.

The Glycemic Response to Infant Formulas: A Randomized Clinical Trial.

BACKGROUND: Commercial infant formulas attempt to imitate human milk's unique composition. However, lactose-free and milk protein-free formulas are often chosen due to medical reasons or personal preferences. The aim of this study was to determine the glycemic and insulinemic indices of a variety of infant formulas. METHODS: We conducted a three-arm, randomized, double-blind, crossover study. Participants were 25-40-year-old healthy adults. Three commercial infant formulas (cow's milk protein-based ["standard"], soy protein-based, and lactose-free) were randomly given to each participant. Glycemic and insulinemic responses were determined and compared between the three formulas. RESULTS: Twenty subjects were enrolled (11 females/9 males, mean age 32.8 ± 2.9 years). No significant difference was found in the glycemic index between the three formulas (21.5, 29.1, and 21.5 for the standard, soy protein-based, and lactose-free formulas, respectively, p = 0.21). However, maximal glucose levels were significantly higher for the soy protein-based formula compared to both the standard and lactose-free formulas (111.5 compared to 101.8 and 105.8 mg/dL, respectively, p = 0.001). CONCLUSION: Cow's milk protein-based, soy protein-based, and lactose-free formulas have a similar glycemic index. However, soy protein-based formula produced a significantly higher increase in postprandial glucose levels. The implication and biological significance of these results have yet to be determined.

Caution, "normal" BMI: health risks associated with potentially masked individual underweight-EPMA Position Paper 2021.

An increasing interest in a healthy lifestyle raises questions about optimal body weight. Evidently, it should be clearly discriminated between the standardised "normal" body weight and individually optimal weight. To this end, the basic principle of personalised medicine "one size does not fit all" has to be applied. Contextually, "normal" but e.g. borderline body mass index might be optimal for one person but apparently suboptimal for another one strongly depending on the individual genetic predisposition, geographic origin, cultural and nutritional habits and relevant lifestyle parameters-all included into comprehensive individual patient profile. Even if only slightly deviant, both overweight and underweight are acknowledged risk factors for a shifted metabolism which, if being not optimised, may strongly contribute to the development and progression of severe pathologies. Development of innovative screening programmes is essential to promote population health by application of health risks assessment, individualised patient profiling and multi-parametric analysis, further used for cost-effective targeted prevention and treatments tailored to the person. The following healthcare areas are considered to be potentially strongly benefiting from the above proposed measures: suboptimal health conditions, sports medicine, stress overload and associated complications, planned pregnancies, periodontal health and dentistry, sleep medicine, eye health and disorders, inflammatory disorders, healing and pain management, metabolic disorders, cardiovascular disease, cancers, psychiatric and neurologic disorders, stroke of known and unknown aetiology, improved individual and population outcomes under pandemic conditions such as COVID-19. In a long-term way, a significantly improved healthcare economy is one of benefits of the proposed paradigm shift from reactive to Predictive, Preventive and Personalised Medicine (PPPM/3PM). A tight collaboration between all stakeholders including scientific community, healthcare givers, patient organisations, policy-makers and educators is essential for the smooth implementation of 3PM concepts in daily practice.

Association between parental self-reported knowledge on soy and phytoestrogen and their children's intake of soy-based infant formulae-a cross-sectional study of Israeli parents.

OBJECTIVES: Though natural phytoestrogen (PE) is a major factor in health authorities' considerations regarding soy-based infant formula (SBIF), missing their concentrations may interfere with parents' informed decision. METHODS: We performed an Internet survey investigating soy-related knowledge of parents. We built multiple logistic regression models adjusted for personal covariates for the association between parental knowledge on PE and children intake of SBIF and checked the effect of having children ≤ 2 years old on this association. RESULTS: We enrolled 304 parents, 48.3% men, mean age 33.8 (standard deviation, SD 4.9), mostly with higher education. Of them, 76% had children under two years of age. Mean parental knowledge on PE was 9.83 (SD 3.28) from 20 possible points. Parental knowledge on PE reduced children's intake of SBIF (odds ratio, OR = 0.85 [95% confidence interval 0.70; 1.02]). Stronger inverse association was found for parents with children ≤ 2 comparing with those with older children (OR = 0.85 [0.67; 1.09] and OR = 0.68 [0.39; 1.18], respectively), although these differences were not statistically significant. CONCLUSIONS: Adding PE content to information on SBIF may support informed decision.

Modified egg as a nutritional supplement during peak brain development: a new target for fortification.

BACKGROUND: Though eggs have the unique capacity, like breastmilk, to concentrate essential nutrients required for early growth and brain development of offspring - i.e. n-3 PUFA, increasingly deficient and sources contaminated - cholesterol and allergy concerns often exclude them from perinatal recommendations. OBJECTIVE: Egg's potential contribution of key nutrients required for peak brain development are re-evaluated vis-à-vis fortification, accessibility, and risks. METHODS: Contributions of standard (USDA) and fortified (selected market-available) egg compositions to perinatal requirements for critical brain-supporting nutrients were compared to human and cow milks, and risks and recommendations evaluated. RESULTS: Standard egg has already higher concentrations/kcal of iron, selenium, zinc, choline, vitamins B12 and E, and essential amino acids (plus taurine) than human milk. Fortified egg could further yield significant n-3 PUFA % recommendations for pregnancy-lactation (total n-3 69.6-75.0% [DRI=1400-1300 mg/day]), including DHA (120.1-129.3%, mostly approximately 80% [calculated DRI=140-130 mg/day]), plus antioxidant vitamins A (9.0-15.2%) and E (51.6-65.3%), and minerals iodine (33.6-44.5%) and selenium (33.7-39.3%); % recommendations for children (1-3 y) even more. Cholesterol, important for nerve membranes and learning, may not be generally contraindicated in childbearing-aged women (approximately 10.5% hypercholesterolemia), and early-life egg exposure may increase tolerance. Egg-inclusive perinatal nutrition programs have shown significant contributions. CONCLUSIONS: Eggs, especially target-fortified, may provide a unique nutritional supplement for peak brain development continously during pregnancy, nursing, and infancy (from 6 months), especially vs. insufficiencies. Missing nutritional opportunities by egg exclusion vs. concerns of hypercholesterolemia or allergy could be addressed individually, rather than as general recommendations, warranting further research and targeted egg design.

The Metabolic Concept of Meal Sequence vs. Satiety: Glycemic and Oxidative Responses with Reference to Inflammation Risk, Protective Principles and Mediterranean Diet.

With increasing exposure to eating opportunities and postprandial conditions becoming dominant states, acute effects of meals are garnering interest. In this narrative review, meal components, combinations and course sequence were questioned vis-à-vis resultant postprandial responses, including satiety, glycemic, oxidative and inflammatory risks/outcomes vs. protective principles, with reference to the Mediterranean diet. Representative scientific literature was reviewed and explained, and corresponding recommendations discussed and illustrated. Starting meals with foods, courses and/or preloads high in innate/added/incorporated water and/or fibre, followed by protein-based courses, delaying carbohydrates and fatty foods and minimizing highly-processed/sweetened hedonic foods, would increase satiety-per-calorie vs. obesogenic passive overconsumption. Similarly, starting with high-water/fibre dishes, followed by high-protein foods, oils/fats, and delayed/reduced slowly-digested whole/complex carbohydrate sources, optionally closing with simpler carbohydrates/sugars, would reduce glycaemic response. Likewise, starting with foods high in innate/added/incorporated water/fibre/antioxidants, high monounsaturated fatty acid foods/oils, light proteins and whole/complex carbohydrate foods, with foods/oils low in n-6 polyunsaturated fatty acids (PUFA) and n-6:n-3 PUFA ratios, and minimal-to-no red meat and highly/ultra-processed foods/lipids, would reduce oxidative/inflammatory response. Pyramids illustrating representative meal sequences, from most-to-least protective foods, visually communicate similarities between axes, suggesting potential unification for optimal meal sequence, consistent with anti-inflammatory nutrition and Mediterranean diet/meal principles, warranting application and outcome evaluation.

Modified egg composition to reduce low-density lipoprotein oxidizability: high monounsaturated fatty acids and antioxidants versus regular high n-6 polyunsaturated fatty acids.

Eggs high in n-6 PUFA, predominant in Western markets, were found to increase blood LDL oxidation, suggesting a new health concern beyond raising cholesterol. Protective composition was explored by increasing egg antioxidants and MUFA and reducing n-6 PUFA. Lag times to plasma LDL oxidation were significantly shortened with two eggs/day of high-PUFA compositions compared to a low-egg (2-4/week) regime, by 28.8% following "HPUFA-regular" ( p < 0.01) and by 27.2% following antioxidant-fortified "HPUFA-HAOX" ( p < 0.01). However, two "HMUFA-HAOX" eggs/day with reduced egg n-6 PUFA FA% (LA by 30.7%) and PUFA:MUFA ratio (LA:OA by 45.8%) plus increased antioxidants (vitamin E 500%, carotenoids 260%), resulting in increased plasma OA 33.3%, vitamin E 22.4%, and carotenoids 55.0% ( p < 0.01), were associated with lag-time only 6.6% shorter than low-egg (NS). Among health-oriented egg modifications, here for the first time they reduced associated LDL oxidization, consistent with anti-inflammation and antioxidant paradigms, warranting further research on functional advantages of antioxidative egg composition.

Egg fortification with n-3 polyunsaturated fatty acids (PUFA): nutritional benefits versus high n-6 PUFA western diets, and consumer acceptance.

BACKGROUND: As high dietary n-6 polyunsaturated fatty acids and n-6:n-3 PUFA ratio may contribute to many western ailments, increasing n-3 PUFA in foods could be beneficial. The nutritional significance of n-3 PUFA-fortified egg vs. enzymatically competitive high n-6 PUFA diets is debatable. OBJECTIVES: To evaluate the dietary contribution of 'field fortification' of eggs by adding n-3 PUFA to high n-6 PUFA hen feed and to assess whether it meets consumer preferences. METHODS: Laying hens (n=3500) were fed n-3 PUFA-fortified (5% extruded linseed) feed or standard (control) feed for 5 weeks. Nutritional significance was evaluated for western (American, Israeli) populations. RESULTS: Compared to regular (control) eggs, fortified eggs yielded a 3.8-fold increase in total n-3 PUFA, 6.4-fold alpha-linolenic acid (18:3), and 2.4-fold docohexaenoic acid 22:6). N-6:n-3 PUFA ratio decreased 3.6-fold, and n-6:n-3 long chain PUFA ratio (AA:DHA) 3.0-fold (P< 0.0003). Sensory evaluations were not significantly different. Egg cost increased by 1.5-3.0%. Fortified egg n-3 PUFA content averaged 14.3% of the current intake of Americans and 15.9% of Israelis - 9.8 and 10.6% of upper Dietary Reference Intakes, respectively. Egg DHA content averaged 33.7 and 41.4% of upper DRI. Current cholesterol intakes average 281 and 263 mg/day (median 214 and 184 mg/day) including 0.7 and 0.5 egg/day; reported hypercholesterolemia rates are 17.7 and 16.5%, respectively. CONCLUSIONS: Effective concentration and transformation of supplemental n-3 PUFA/LCPUFA from feed to egg substantially enhanced egg n-3 PUFA %DRI, particularly of DHA, critical for health but often deficient. Such land-based n-3 PUFA/LCPUFA fortification may be applicable to high n-6 PUFA diets, fitting within cholesterol limitations and market criteria. It may contribute to general health and specific requirements (i.e., pregnancy and lactation), with possibilities of wide accessibility and standardization.

Israeli 'cancer shift' over heart disease mortality may be led by greater risk in women with high intake of n-6 fatty acids.

My hypothesis is that higher female sensitivity to increased n-6 polyunsaturated fatty acids and their carcinogenic effect may contribute to the recent Israeli 'cancer shift' over heart disease mortality (23.1 vs. 22.3%, 1999). High n-6 polyunsaturated fatty acid intake was the presumed dietary risk underlying the 'Israeli paradox', the unexpected gap between 'ill' health and 'good' diet. Scientific literature and population health surveillance reports were reviewed. Cancer death rates for Israeli Arabs, who consumed a more traditional Mediterranean diet - more monounsaturated fatty acids, mostly olive oil, and less n-6 polyunsaturated fatty acids - are still 1.1-1.7 times (men-women) lower than in Israeli Jews, but are increasing faster (23.6 and 5.1% vs. 5.3 and -3.3%, 1980-2000), concurrently with dietary 'Israelization' - specifically, increased intake of n-6 polyunsaturated fatty acids. Israeli-Jewish women attained an earlier, much larger (29 vs. 7%, 1999) 'cancer : heart disease mortality shift' (ratio >1.0), ranked much worse for cancer (15th/44 European countries) than men (37th) and heart disease (38th and 34th, respectively), and had much higher cancer prevalence (1 : 3) than Israeli-Arab women (1 : 6), though dietary compositions were similar, save for higher n-6 polyunsaturated fatty acid and polyunsaturated fatty acid : monounsaturated fatty acid ratio. Population studies of Israeli Jews, Arabs, and women support the association of high n-6 polyunsaturated fatty acid intake with increased cancer risk and higher female sensitivity. Research findings suggest that gender and sex hormones may influence n-6 polyunsaturated fatty acid metabolism and carcinogenesis. This appears to be the first time gender has been proposed to modulate national cancer epidemiology, suggesting implications for differential nutritional prevention, warranting further research.

The potential contribution of dietary factors to breast cancer prevention.

Breast cancer (BC), the leading cancer in women, is increasing in prevalence worldwide, concurrent with western metabolic epidemics, that is, obesity, metabolic syndrome, and diabetes, and shares major risk factors with these diseases. The corresponding potential for nutritional contributions toward BC prevention is reviewed and related to critical stages in the life cycle and their implications for carcinogenic and pathometabolic trajectories. BC initiation potentially involves diet-related pro-oxidative, inflammatory, and procarcinogenic processes, that interact through combined lipid/fatty acid peroxidation, estrogen metabolism, and related DNA-adduct/depurination/mutation formation. The pathometabolic trajectory is affected by high estrogen, insulin, and growth factor cascades and resultant accelerated proliferation/progression. Anthropometric risk factors - high birth weight, adult tallness, adiposity/BMI, and weight gain - are often reflective of these trends. A sex-based nutritional approach targets women's specific risk in western obesogenic environments, associated with increasing fatness, estrogen metabolism, n-6 : n-3 polyunsaturated fatty acid ratio, and n-6 polyunsaturated fatty acid conversion to proinflammatory/carcinogenic eicosanoids, and effects of timing of life events, for example, ages at menarche, full-term pregnancy, and menopause. Recent large-scale studies have confirmed the effectiveness of the evidence-based recommendations against BC risk, emphasizing low-energy density diets, highly nutritious plant-based regimes, physical activity, and body/abdominal adiposity management. Better understanding of dietary inter-relationships with BC, as applied to food intake, selection, combination, and processing/preparation, and recommended patterns, for example, Mediterranean, DASH, plant-based, low energy density, and low glycemic load, with high nutrient/phytonutrient density, would increase public motivation and authoritative support for early/timely prevention, optimally merging with other dietary/health goals, for lifelong BC prevention.

Bioavailability of Petit-Suisse cheese as food vehicle for iron fortification estimated by the prophylactic method.

Microencapsulated ferrous sulfate (SFE-171) and ferric orthophosphate in Petit-Suisse cheese were examined for iron bioavailability by the prophylactic method. The iron sources were industrially added to different samples of Petit-Suisse cheese, which were mixed with other food components in our laboratory before use. A reference standard diet inclusive of nonmicroencapsulated ferrous sulfate and a control diet low in iron content were prepared in the laboratory. The final iron content in the fortified diets was approximately 15 mg Fe/kg diet. These diets were administered to weaning rats for 23 days. The iron bioavailability was evaluated as the ratio of iron incorporated into hemoglobin to oral iron intake, thereby being estimated as 62.6 +/- 8.8% for ferrous sulfate and 59.2 +/- 10.6% for SFE-171, which were significantly effective at p < 0.01 compared to 43.4 +/- 10.5% for ferric orthophosphate. It thus turned out that SFE-171 was stable through industrial processing with Petit-Suisse cheese as the food vehicle and served as an iron fortifier equal to ferrous sulfate in bioavailability.

Women's higher health risks in the obesogenic environment: a gender nutrition approach to metabolic dimorphism with predictive, preventive, and personalised medicine.

Women's evolution for nurturing and fat accumulation, which historically yielded health and longevity advantages against scarcity, may now be counteracted by increasing risks in the obesogenic environment, recently shown by narrowing gender health gap. Women's differential metabolism/disease risks, i.e. in fat accumulation/distribution, exemplified during puberty/adolescence, suggest gender dimorphism with obesity outcomes. Women's higher body fat percentage than men, even with equal body mass index, may be a better risk predictor. Differential metabolic responses to weight-reduction diets, with women's lower abdominal fat loss, better response to high-protein vs. high-carbohydrate diets, higher risks with sedentariness vs. exercise benefits, and tendency toward delayed manifestation of central obesity, metabolic syndrome, diabetes, cardiovascular disease, and certain cancers until menopause-but accelerated thereafter-suggest a need for differing metabolic and chronological perspectives for prevention/intervention. These perspectives, including women's differential responses to lifestyle changes, strongly support further research with a gender nutrition emphasis within predictive, preventive, and personalized medicine.

Nutritional approach to sun protection: a suggested complement to external strategies.

The increasing incidence of skin cancer despite the use of externally applied sun protection strategies, alongside research showing that nutrients reduce photo-oxidative damage, suggest nutritional approaches could play a beneficial role in skin cancer prevention. Penetrating photo-oxidative ultraviolet A radiation reduces skin and blood antioxidants and damages cell components, including DNA. Dietary antioxidant vitamins, minerals, and phytochemicals in addition to n-3 polyunsaturated fatty acids, n-9 monounsaturated fatty acids, and low pro-inflammatory n-6 polyunsaturated fatty acids, have demonstrated protective properties. The presence of these elements in the traditional Greek-style Mediterranean diet may have contributed to the low rates of melanoma in the Mediterranean region despite high levels of solar radiation. This suggests a potentially relevant model for studying dietary/nutritional supplementation for lifelong internal support of sun-protection mechanisms, which could complement external strategies.

n-3 PUFA fortification of high n-6 PUFA farmed tilapia with linseed could significantly increase dietary contribution and support nutritional expectations of fish.

Farmed fish high in n-6 PUFA may undermine fish nutritional expectations and intake recommendations for n-3 PUFA requirements and exacerbate rather than improve already high n-6/n-3 PUFA diets. Dietary contribution of fish fortification by linseed-based n-3 PUFA was evaluated. Mango tilapia (12 months old) with high n-6 PUFA (21.8 FA%, n-6/n-3 ratio 4.6:1) were fed standard/control (T(C)) or linseed-supplemented (5%, T(5%); 7%, T(7%)) feed for 61 days regular-growth and 120 days stock-growth (to 650 g). Compared to T(C), n-3 PUFA increased in T(5%) 46% and T(7%) 58%; ALA in T(5%) increased 100% and T(7%) 167%; EPA+DHA in T(5%) increased 14% and T(7%) 23% (p < 0.05); n-6 PUFA/LCPUFA were unchanged. T(7%) EPA+DHA 168 mg/100 g of raw fillet is comparable to current American intake and Dietary Reference Intakes; controlled cooking preserved approximately 90% EPA+DHA. n-6/n-3 ratios decreased 16-38% in total PUFA to 2.3:1 and in LCPUFA to 0.61:1. Linseed supplementation could improve tilapia n-3 PUFA/LCPUFA, ameliorating n-3 PUFA scarcity and unexpectedly high fish n-6 PUFA content, potentially making a significant nutritional contribution.

Prenatal nutrition: a critical window of opportunity for mother and child.

The prenatal period encompasses a critical window for future health and functioning of mother and child. Attention previously focused on undernutrition risk (i.e., in developing countries and famine conditions) shifted to mismatch between prenatal 'programming' by undernutrition and postnatal overconsumption (i.e., low birthweight vs rapid postnatal growth), now to overconsumption/overweight throughout the reproductive cycle and short- and long-term health risks, including obesity, diabetes, dyslipidemia and cardiovascular disease. Moreover, overconsumption/overweight do not guarantee adequacy of critical nutrients (i.e., against birth defects or for brain development). Multinutrient supplementation - including zinc, iodine, choline and long-chain polyunsaturated fatty acids, especially n-3 - may have advantages over single-nutrient supplements, for example, iron or folate. Future nutritional care for healthy in utero programming may necessitate individual assessment and follow-up, including preconception nutritional preparation, appropriate weight gain, metabolic balance and food-based regimens enhanced by key nutrient fortification and/or supplementation, warranting further research into nutritional optimization of pregnancy outcomes.