Diets, nutrients, genes and the microbiome: recent advances in personalised nutrition.

As individuals seek increasingly individualised nutrition and lifestyle guidance, numerous apps and nutrition programmes have emerged. However, complex individual variations in dietary behaviours, genotypes, gene expression and composition of the microbiome are increasingly recognised. Advances in digital tools and artificial intelligence can help individuals more easily track nutrient intakes and identify nutritional gaps. However, the influence of these nutrients on health outcomes can vary widely among individuals depending upon life stage, genetics and microbial composition. For example, folate may elicit favourable epigenetic effects on brain development during a critical developmental time window of pregnancy. Genes affecting vitamin B12 metabolism may lead to cardiometabolic traits that play an essential role in the context of obesity. Finally, an individual's gut microbial composition can determine their response to dietary fibre interventions during weight loss. These recent advances in understanding can lead to a more complete and integrated approach to promoting optimal health through personalised nutrition, in clinical practice settings and for individuals in their daily lives. The purpose of this review is to summarise presentations made during the DSM Science and Technology Award Symposium at the 13th European Nutrition Conference, which focused on personalised nutrition and novel technologies for health in the modern world.

Perspective: Guiding Principles for the Implementation of Personalized Nutrition Approaches That Benefit Health and Function.

Personalized nutrition (PN) approaches have been shown to help drive behavior change and positively influence health outcomes. This has led to an increase in the development of commercially available PN programs, which utilize various forms of individual-level information to provide services and products for consumers. The lack of a well-accepted definition of PN or an established set of guiding principles for the implementation of PN creates barriers for establishing credibility and efficacy. To address these points, the North American Branch of the International Life Sciences Institute convened a multidisciplinary panel. In this article, a definition for PN is proposed: "Personalized nutrition uses individual-specific information, founded in evidence-based science, to promote dietary behavior change that may result in measurable health benefits." In addition, 10 guiding principles for PN approaches are proposed: 1) define potential users and beneficiaries; 2) use validated diagnostic methods and measures; 3) maintain data quality and relevance; 4) derive data-driven recommendations from validated models and algorithms; 5) design PN studies around validated individual health or function needs and outcomes; 6) provide rigorous scientific evidence for an effect on health or function; 7) deliver user-friendly tools; 8) for healthy individuals, align with population-based recommendations; 9) communicate transparently about potential effects; and 10) protect individual data privacy and act responsibly. These principles are intended to establish a basis for responsible approaches to the evidence-based research and practice of PN and serve as an invitation for further public dialog. Several challenges were identified for PN to continue gaining acceptance, including defining the health-disease continuum, identification of biomarkers, changing regulatory landscapes, accessibility, and measuring success. Although PN approaches hold promise for public health in the future, further research is needed on the accuracy of dietary intake measurement, utilization and standardization of systems approaches, and application and communication of evidence.

US Family Physicians Overestimate Personal ω-3 Fatty Acid Biomarker Status: Associations with Fatty Fish and ω-3 Supplement Intake.

BACKGROUND: The health benefits of ω-3 (n-3) fatty acids are well established. Only a small percentage of Americans consume the recommended amounts of fatty fish, the main dietary source of ω-3 fatty acids, and most have low ω-3 fatty acid blood concentrations. OBJECTIVE: We aimed to measure biomarkers of long-chain ω-3 fatty acid (EPA and DHA) status among family physicians, and determine whether having their ω-3 status tested would influence attitudes and patient recommendations. METHODS: Family physicians attending a medical conference (n = 340) completed an ω-3 intake survey and had a finger stick blood sample taken. ω-3 Index, percentage of ω-6 (%n-6) in highly unsaturated fatty acids (HUFAs), and EPA:arachidonic acid (AA) ratio were calculated from whole blood fatty acid profiles. Post-conference, a subsample of participants (n = 100) responded to a survey regarding attitudes and recommendations about ω-3s. RESULTS: Average age (mean ± SEM) of participants was 48.0 ± 0.7 y and 59% were women. Average ω-3 Index was 5.2% ± 0.1%, %n-6 in HUFA was 75% ± 0.4%, and EPA:AA ratio was 0.076 ± 0.004. 57% of family physicians reported consuming <2 servings/wk of fatty fish, and 78% reported using ω-3 supplements ≤1/wk. Although 51% believed ω-3 status was in a desirable range, only 5% had an ω-3 Index ≥8%. Biomarkers of ω-3 status were significantly associated with fatty fish intake and supplement use, and were correlated (R2 ranging from 0.59 to 0.77). Physicians who had ω-3 status tested (n = 65) were more likely to agree with statements affirming the health benefits of ω-3 fatty acids and more willing to recommend ω-3 fatty acids to their patients (P = 0.004). CONCLUSIONS: Blood concentrations of ω-3 fatty acids in family physicians were below recommendations, and were associated with fatty fish intake and ω-3 supplement use. There was a discrepancy between perceived and actual ω-3 status. Increased awareness of personal ω-3 status among physicians may facilitate patient communication and recommendations about ω-3 fatty acid intake. This trial was registered at clinicaltrials.gov as, NCT03056898.

Implications of US Nutrition Facts Label Changes on Micronutrient Density of Fortified Foods and Supplements.

The US FDA published new nutrition-labeling regulations in May 2016. For the first time since the implementation of the Nutrition Labeling and Education Act of 1990, the Daily Value (DV) for most vitamins will change, as will the units of measurement used in nutrition labeling for some vitamins. For some food categories, the Reference Amounts Customarily Consumed (RACCs) will increase to reflect portions commonly consumed on a single occasion. These regulatory changes are now effective, and product label changes will be mandatory beginning 26 July 2018. This commentary considers the potential impact of these regulatory changes on the vitamin and mineral contents of foods and dietary supplements. Case studies examined potential effects on food fortification and nutrient density. The updated DVs may lead to a reduction in the nutrient density of foods and dietary supplements with respect to 8 vitamins (vitamin A, thiamin, riboflavin, niacin, vitamin B-6, vitamin B-12, biotin, and pantothenic acid) and 6 minerals (zinc, selenium, copper, chromium, molybdenum, and chloride), and have mixed effects on 2 vitamins where the amount required per serving is affected by chemical structure (i.e., form) (natural vitamin E compared with synthetic vitamin E and folic acid compared with folate). Despite an increased DV for vitamin D, regulations limit food fortification. The adoption of Dietary Folate Equivalents for folate labeling may lead to reductions in the quantity of folic acid voluntarily added per RACC. Finally, because of increased RACCs in some food categories to reflect portions that people typically eat at one time, the vitamin and mineral density of these foods may be affected adversely. In totality, the United States is entering an era in which the need to monitor dietary intake patterns and nutritional status is unprecedented.

Chocolate matrix factors modulate the pharmacokinetic behavior of cocoa flavan-3-ol phase II metabolites following oral consumption by Sprague-Dawley rats.

The impact of carbohydrates and milk on the bioavailability of catechin (C) and epicatechin (EC) from chocolate has been previously studied. However, little data exist regarding potential modulation of the phase II metabolism by these chocolate matrix factors. The objectives of this study were to assess the impact of matrix composition on qualitative and quantitative profiles of circulating catechins and their metabolites following administration of commercially relevant chocolate confections. Sprague-Dawley rats were administered 1.5 g of a confection (reference dark, high sucrose, or milk chocolate) by intragastric gavage, and plasma samples were collected over 8 h. High-performance liquid chromatography-mass spectrometry analysis was performed to quantify C, EC, and their metabolites. The predominant metabolites were O-glucuronides (two metabolites) and O-Me-O-glucuronides (three metabolites). Plasma concentrations of metabolites were generally the highest for high sucrose treatment and lowest for milk treatment, while the reference dark treatment generally resulted in intermediate concentrations. The O-Me-(+/-)-C/EC-O-beta-glucuronide (peak 4) was significantly higher for the high sucrose treatment (2325 nM h) versus the milk treatment (1300 nM h). Additionally, C(MAX) values for (+/-)-C/EC-O-beta-glucuronide (peak 3) and two O-Me-(+/-)-C/EC-O-beta-glucuronides (peaks 4 and 6) were significantly higher for the high sucrose treatment (4012, 518, and 2518 nM, respectively) versus the milk treatment (2590, 240, and 1670 nM, respectively). Milk and sucrose appear to modulate both metabolism and plasma pharmacokinetics and, to a lesser extent, the overall bioavailability of catechins from chocolate confections.

Influence of chocolate matrix composition on cocoa flavan-3-ol bioaccessibility in vitro and bioavailability in humans.

Conflicting data exist regarding the influence of chocolate matrices on the bioavailability of epicatechin (EC) from cocoa. The objective of this study was to assess the bioavailability of EC from matrices varying in macronutrient composition and physical form. EC bioavailability was assessed from chocolate confections [reference dark chocolate (CDK), high sucrose (CHS), high milk protein (CMP)] and cocoa beverages [sucrose milk protein (BSMP), non-nutritive sweetener milk protein (BNMP)], in humans and in vitro. Six subjects consumed each product in a randomized crossover design, with serum EC concentrations monitored over 6 h post consumption. Areas under the serum concentration-time curve (AUC) were similar among chocolate matrices. However, AUCs were significantly increased for BSMP and BNMP (132 and 143 nM h) versus CMP (101 nM h). Peak serum concentrations (C(MAX)) were also increased for BSMP and BNMP (43 and 42 nM) compared to CDK and CMP (32 and 25 nM). Mean T(MAX) values were lower, although not statistically different, for beverages (0.9-1.1 h) versus confections (1.8-2.3 h), reflecting distinct shapes of the pharmacokinetic curves for beverages and confections. In vitro bioaccessibility and Caco-2 accumulation did not differ between treatments. These data suggest that bioavailability of cocoa flavan-3-ols is likely similar from typical commercial cocoa based foods and beverages, but that the physical form and sucrose content may influence T(MAX) and C(MAX).

Epithiospecifier protein from broccoli (Brassica oleracea L. ssp. italica) inhibits formation of the anticancer agent sulforaphane.

In some cruciferous plants, epithiospecifier protein (ESP) directs myrosinase (EC 3.2.3.1)-catalyzed hydrolysis of alkenyl glucosinolates toward epithionitrile formation. Here, for the first time, we show that ESP activity is negatively correlated with the extent of formation of the health-promoting phytochemical sulforaphane in broccoli (Brassica oleracea L. ssp. italica). A 43 kDa protein with ESP activity and sequence homology to the ESP of Arabidopsis thaliana was cloned from the broccoli cv. Packman and expressed in Escherichia coli. In a model system, the recombinant protein not only directed myrosinase-dependent metabolism of the alkenyl glucosinolate epi-progoitrin [(2S)-2-hydroxy-3-butenyl glucosinolate] toward formation of an epithionitrile but also directed myrosinase-dependent hydrolysis of the glucosinolate glucoraphanin [4-(methylsulfinyl)butyl glucosinolate] to form sulforaphane nitrile, in place of the isothiocyanate sulforaphane. The importance of this finding is that, whereas sulforaphane has been shown to have anticarcinogenic properties, sulforaphane nitrile has not. Genetic manipulation designed to attenuate or eliminate expression of ESP in broccoli could increase the fractional conversion of glucoraphanin to sulforaphane, enhancing potential health benefits.

Sulforaphane prevents mouse skin tumorigenesis during the stage of promotion.

Sulforaphane (SF), a natural product from broccoli, is known to enhance detoxification of carcinogens and block initiation of chemically-induced carcinogenesis in animal models. Cell culture and xenograft studies suggest additional roles for SF, inhibiting growth of tumors, arresting the cell cycle and enhancing apoptosis. As currently reported, topical SF (1, 5 or 10 micromol/mouse) significantly inhibited 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol 13-acetate (TPA)-induced mouse skin tumorigenesis, using either an anti-promotion protocol (SF from 1 week after carcinogen until the end of the study) or a combined anti-initiation, anti-promotion protocol (SF 7 days prior to carcinogen until the end of the study). Surprisingly, no significant effect was observed in an anti-initiation protocol (SF from 7 days prior to 7 days after carcinogen). Separately, SF inhibited TPA-induced ornithine decarboxylase activity in mouse skin, an obligate step in TPA-induced promotion of carcinogenesis. These data link this molecular mechanism to SF-dependent inhibition of the promotion of tumorigenesis.

Heating decreases epithiospecifier protein activity and increases sulforaphane formation in broccoli.

Sulforaphane, an isothiocyanate from broccoli, is one of the most potent food-derived anticarcinogens. This compound is not present in the intact vegetable, rather it is formed from its glucosinolate precursor, glucoraphanin, by the action of myrosinase, a thioglucosidase enzyme, when broccoli tissue is crushed or chewed. However, a number of studies have demonstrated that sulforaphane yield from glucoraphanin is low, and that a non-bioactive nitrile analog, sulforaphane nitrile, is the primary hydrolysis product when plant tissue is crushed at room temperature. Recent evidence suggests that in Arabidopsis, nitrile formation from glucosinolates is controlled by a heat-sensitive protein, epithiospecifier protein (ESP), a non-catalytic cofactor of myrosinase. Our objectives were to examine the effects of heating broccoli florets and sprouts on sulforaphane and sulforaphane nitrile formation, to determine if broccoli contains ESP activity, then to correlate heat-dependent changes in ESP activity, sulforaphane content and bioactivity, as measured by induction of the phase II detoxification enzyme quinone reductase (QR) in cell culture. Heating fresh broccoli florets or broccoli sprouts to 60 degrees C prior to homogenization simultaneously increased sulforaphane formation and decreased sulforaphane nitrile formation. A significant loss of ESP activity paralleled the decrease in sulforaphane nitrile formation. Heating to 70 degrees C and above decreased the formation of both products in broccoli florets, but not in broccoli sprouts. The induction of QR in cultured mouse hepatoma Hepa lclc7 cells paralleled increases in sulforaphane formation.