Maternal dietary fatty acid composition and newborn epigenetic aging-a geometric framework approach.

BACKGROUND: Maternal nutrition is associated with epigenetic and cardiometabolic risk factors in offspring. Research in humans has primarily focused on assessing the impact of individual nutrients. OBJECTIVES: We sought to assess the collective impact of maternal dietary MUFAs, PUFAs, and SFAs on epigenetic aging and cardiometabolic risk markers in healthy newborn infants using a geometric framework approach. METHODS: Body fatness (n = 162), aortic intima-media thickness (aIMT; n = 131), heart rate variability (n = 118), and epigenetic age acceleration (n = 124) were assessed in newborn infants. Maternal dietary intake was cross-sectionally assessed in the immediate postpartum period via a validated 80-item self-administered FFQ. Generalized additive models were used to explore interactive associations of nutrient intake, with results visualized as response surfaces. RESULTS: After adjustment for total energy intake, maternal age, gestational age, and sex there was a 3-way interactive association of MUFAs, PUFAs, and SFAs (P = 0.001) with newborn epigenetic aging. This suggests that the nature of each fat class association depends upon one another. Response surfaces revealed MUFAs were positively associated with newborn epigenetic age acceleration only at proportionately lower intakes of SFAs or PUFAs. We also demonstrate a potential beneficial association of omega-3 (n-3) PUFAs with newborn epigenetic age acceleration (P = 0.008). There was no significant association of fat class with newborn aIMT, heart rate variability, or body fatness. CONCLUSIONS: In this study, we demonstrated an association between maternal dietary fat class composition and epigenetic aging in newborns. Future research should consider other characteristics such as the source of maternal dietary fatty acids.

Assessment of the Methods Used to Develop Vitamin D and Calcium Recommendations-A Systematic Review of Bone Health Guidelines.

BACKGROUND: There are numerous guidelines developed for bone health. Yet, it is unclear whether the differences in guideline development methods explain the variability in the recommendations for vitamin D and calcium intake. The objective of this systematic review was to collate and compare recommendations for vitamin D and calcium across bone health guidelines, assess the methods used to form the recommendations, and explore which methodological factors were associated with these guideline recommendations. METHODS: We searched MEDLINE, EMBASE, CINAHL, and other databases indexing guidelines to identify records in English between 2009 and 2019. Guidelines or policy statements on bone health or osteoporosis prevention for generally healthy adults aged ≥40 years were eligible for inclusion. Two reviewers independently extracted recommendations on daily vitamin D and calcium intake, supplement use, serum 25 hydroxyvitamin D [25(OH)D] level, and sunlight exposure; assessed guideline development methods against 25 recommended criteria in the World Health Organization (WHO) handbook for guideline development; and, identified types identified types of evidence underpinning the recommendations. RESULTS: we included 47 eligible guidelines from 733 records: 74% of the guidelines provided vitamin D (200~600-4000 IU/day) and 70% provided calcium (600-1200 mg/day) recommendations, 96% and 88% recommended vitamin D and calcium supplements, respectively, and 70% recommended a specific 25(OH)D concentration. On average, each guideline met 10 (95% CI: 9-12) of the total of 25 methodological criteria for guideline development recommended by the WHO Handbook. There was uncertainty in the association between the methodological criteria and the proportion of guidelines that provided recommendations on daily vitamin D or calcium. Various types of evidence, including previous bone guidelines, nutrient reference reports, systematic reviews, observational studies, and perspectives/editorials were used to underpin the recommendations. CONCLUSIONS: There is considerable variability in vitamin D and calcium recommendations and in guideline development methods in bone health guidelines. Effort is required to strengthen the methodological rigor of guideline development and utilize the best available evidence to underpin nutrition recommendations in evidence-based guidelines on bone health.

Global associations between macronutrient supply and age-specific mortality.

Animal experiments have demonstrated that energy intake and the balance of macronutrients determine life span and patterns of age-specific mortality (ASM). Similar effects have also been detected in epidemiological studies in humans. Using global supply data and 1,879 life tables from 103 countries, we test for these effects at a macrolevel: between the nutrient supplies of nations and their patterns of ASM. We find that macronutrient supplies are strong predictors of ASM even after correction for time and economic factors. Globally, signatures of undernutrition are evident in the effects of low supply on life expectancy at birth and high mortality across ages, even as recently as 2016. However, in wealthy countries, the effects of overnutrition are prominent, where high supplies particularly from fats and carbohydrates are predicted to lead to high levels of mortality. Energy supplied at around 3,500 kcal/cap/d minimized mortality across ages. However, we show that the macronutrient composition of energy supply that minimizes mortality varies with age. In early life, 40 to 45% energy from each of fat and carbohydrate and 16% from protein minimizes mortality. In later life, replacing fat with carbohydrates to around 65% of total energy and reducing protein to 11% is associated with the lowest level of mortality. These results, particularly those regarding fats, accord both with experimental data from animals and within-country epidemiological studies on the association between macronutrient intake and risk of age-related chronic diseases.

Best be(e) on low fat: linking nutrient perception, regulation and fitness.

Preventing malnutrition through consuming nutritionally appropriate resources represents a challenge for foraging animals. This is due to often high variation in the nutritional quality of available resources. Foragers consequently need to evaluate different food sources. However, even the same food source can provide a plethora of nutritional and non-nutritional cues, which could serve for quality assessment. We show that bumblebees, Bombus terrestris, overcome this challenge by relying on lipids as nutritional cue when selecting pollen. The bees 'prioritised' lipid perception in learning experiments and avoided lipid consumption in feeding experiments, which supported survival and reproduction. In contrast, survival and reproduction were severely reduced by increased lipid contents. Our study highlights the importance of fat regulation for pollen foraging bumblebees. It also reveals that nutrient perception, nutrient regulation and reproductive fitness can be linked, which represents an effective strategy enabling quick foraging decisions that prevent malnutrition and maximise fitness.

Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control.

Elevated branched chain amino acids (BCAAs) are associated with obesity and insulin resistance. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets leads to hyperphagia, obesity and reduced lifespan. These effects are not due to elevated BCAA per se or hepatic mTOR activation, but rather due to a shift in the relative quantity of dietary BCAAs and other AAs, notably tryptophan and threonine. Increasing the ratio of BCAAs to these AAs resulted in hyperphagia and is associated with central serotonin depletion. Preventing hyperphagia by calorie restriction or pair-feeding averts the health costs of a high BCAA diet. Our data highlight a role for amino acid quality in energy balance and show that health costs of chronic high BCAA intakes need not be due to intrinsic toxicity but, rather, a consequence of hyperphagia driven by AA imbalance.

Nutritional Ecology and Human Health.

In contrast to the spectacular advances in the first half of the twentieth century with micronutrient-related diseases, human nutrition science has failed to stem the more recent rise of obesity and associated cardiometabolic disease (OACD). This failure has triggered debate on the problems and limitations of the field and what change is needed to address these. We briefly review the two broad historical phases of human nutrition science and then provide an overview of the main problems that have been implicated in the poor progress of the field with solving OACD. We next introduce the field of nutritional ecology and show how its ecological-evolutionary foundations can enrich human nutrition science by providing the theory to help address its limitations. We end by introducing a modeling approach from nutritional ecology, termed nutritional geometry, and demonstrate how it can help to implement ecological and evolutionary theory in human nutrition to provide new direction and to better understand and manage OACD.

An assessment of the influence of macronutrients on growth performance and nutrient utilisation in broiler chickens by nutritional geometry.

The right-angled triangle mixture experiment was designed to include fourteen diets with different concentrations of starch, protein and lipid. Experimental diets were offered to male Ross 308 broiler chickens from 10 to 23 d after hatching, and response curves and surfaces were generated to illustrate the influence of macronutrients on growth performance and nutrient utilisations. Despite the primary function of macronutrients, especially protein, may not be providing energy, macronutrients were expressed as energy derived from starch, protein and fat for statistical purposes in the mixture design. Energy derived from lipid had a greater impact on feed intake than energy derived from starch and protein. When we compared the influence of starch and protein on feed intake, 'equal distance rule' was observed, which means the animal consumes feed to the point on its respective nutritional rails where the shortage of starch exactly equals the surplus of consumed protein. Increasing the protein-derived energy intake increased weight gain in broiler chickens, whereas energy intake derived from starch and lipid had little impact on weight gain. Feed conversion ratio (FCR) may be reduced by either increasing protein energy intake or decreasing starch energy intake. As the slope of the contours was less than 1, the influence of starch energy intakes on FCR exceeded that of protein energy intakes. In conclusion, energy derived from protein is more important than non-protein energy in terms of weight gain, and a balance between protein and energy supplies is required for efficient muscle protein deposition.

Nutritional contributions of insects to primate diets: implications for primate evolution.

Insects and other invertebrates form a portion of many living and extinct primate diets. We review the nutritional profiles of insects in comparison with other dietary items, and discuss insect nutrients in relation to the nutritional needs of living primates. We find that insects are incorporated into some primate diets as staple foods whereby they are the majority of food intake. They can also be incorporated as complements to other foods in the diet, providing protein in a diet otherwise dominated by gums and/or fruits, or be incorporated as supplements to likely provide an essential nutrient that is not available in the typical diet. During times when they are very abundant, such as in insect outbreaks, insects can serve as replacements to the usual foods eaten by primates. Nutritionally, insects are high in protein and fat compared with typical dietary items like fruit and vegetation. However, insects are small in size and for larger primates (>1 kg) it is usually nutritionally profitable only to consume insects when they are available in large quantities. In small quantities, they may serve to provide important vitamins and fatty acids typically unavailable in primate diets. In a brief analysis, we found that soft-bodied insects are higher in fat though similar in chitin and protein than hard-bodied insects. In the fossil record, primates can be defined as soft- or hard-bodied insect feeders based on dental morphology. The differences in the nutritional composition of insects may have implications for understanding early primate evolution and ecology.

Regulation of nutrient intake in nectar-feeding birds: insights from the geometric framework.

A nectar diet is simple in nutritional composition and easily digested, but may vary greatly in its proportions of sugar and water. Here, we apply the geometric framework, a modelling approach for investigating how animals balance nutrient needs in multidimensional and dynamic nutritional environments, to captive whitebellied sunbirds (Cinnyris talatala). We address the question of how these small birds (~8 g) prioritise sugar and water intake, and how dietary salt content interacts with sugar and water intake. Sunbirds kept at 20°C and provided with moderate to high sucrose concentrations (≥1 M), together with supplementary water, converge on an intake target of 2.79 g day(-1) of sucrose and 7.72 g day(-1) of water: equivalent to 0.85 M sucrose. When the birds are given more dilute sucrose concentrations, they defend their sugar intake by over-ingesting water, up to a ceiling of 47 g day(-1). Sugar intake thus gets priority over water intake, but the birds have a finite capacity to over-ingest water to gain the target level of sugar. Regulation appears to be less precise when birds are given a choice between two sucrose solutions than when they choose between a sugar solution and supplementary water. Intake targets vary in response to internal and external factors, and sunbirds increase their sugar intake in response to increased activity and cold, irrespective of nectar concentration. They also compensate for interruptions in foraging activity, whether overnight or during the day. Interactive effects become evident when sodium is included as a third nutrient: on very dilute nectar (≤0.1 M), where sunbirds lose body mass, the addition of sodium to the diet helps to achieve the carbohydrate intake target, while raising the ceiling on water intake. This analysis provides a new perspective on nectarivory, while adding to the comparative database on nutrient regulation and emphasising water as a nutrient.

Dietary ratio of protein to carbohydrate induces plastic responses in the gastrointestinal tract of mice.

Some vertebrates change the size of their digestive system in response to quantity and fibre content of ingested food, but the effects of dietary nutrients on gut structure remain poorly understood. Here we investigate how the protein to carbohydrate ratio of diets affects the mass of the gastrointestinal tract in mice. We fed 6-week-old male mice one of five isocaloric diets differing only in protein to carbohydrate ratio (the "no-choice" treatments), while a further four treatment groups received nutritionally complementary food pairings from which they could self-select a diet (the "choice" treatments). After 32 days, we measured the resulting dry mass of stomachs, intestines, caeca and colons. In the no-choice treatments, the stomachs were heavier in the mice fed diets containing more protein and less carbohydrate, indicating that larger stomachs may be needed for efficient digestion of the protein-rich food. In contrast, intestines, caeca and colons were heavier when diets contained more carbohydrates and less protein. This response may function to increase the digestive rate of carbohydrates when the dietary content of this macronutrient increases, but it may also indicate a compensatory response to increase amino acid uptake from a protein-deficient food. Mice in the choice treatments self-selected a diet with a protein to carbohydrate ratio of 0.46, and had gut dimensions similar to the expectation derived from no-choice treatments for this diet composition. Our results provide an example of plasticity in the differential allocation of resources to organ function, which is triggered by variation in resource quality.

Protein-leverage in mice: the geometry of macronutrient balancing and consequences for fat deposition.

OBJECTIVE: The Protein-Leverage Hypothesis proposes that humans regulate their intake of macronutrients and that protein intake is prioritized over fat and carbohydrate intake, causing excess energy ingestion when diets contain low %protein. Here we test in a model animal, the mouse: (i) the extent to which intakes of protein and carbohydrate are regulated; (ii) if protein intake has priority over carbohydrates so that unbalanced foods low in %protein leads to increased energy intake; and (iii) how such variations in energy intake are converted into growth and storage. METHODS AND PROCEDURES: We fed mice one of five isocaloric foods having different protein to carbohydrate composition, or a combination of two of these foods (N = 15). Nutrient intake and corresponding growth in lean body mass and lipid mass were measured. Data were analyzed using a geometric approach for analyzing intake of multiple nutrients. RESULTS: (i) Mice fed different combinations of complementary foods regulated their intake of protein and carbohydrate toward a relatively well-defined intake target. (ii) When mice were offered diets with fixed protein to carbohydrate ratio, they regulated the intake of protein more strongly than carbohydrate. This protein-leverage resulted in higher energy consumption when diets had lower %protein and led to increased lipid storage in mice fed the diet containing the lowest %protein. DISCUSSION: Although the protein-leverage in mice was less than what has been proposed for humans, energy intakes were clearly higher on diets containing low %protein. This result indicates that tight protein regulation can be responsible for excess energy ingestion and higher fat deposition when the diet contains low %protein.

A comparison of nutrient regulation between solitarious and gregarious phases of the specialist caterpillar, Spodoptera exempta (Walker).

Nutritional regulatory responses were compared between solitarious and gregarious phases of the African armyworm, Spodoptera exempta. When allowed to mix between two nutritionally imbalanced but complementary foods, final-instar caterpillars in both phases selected a diet comprising more carbohydrate than protein. This contrasts with other larval lepidopterans studied to date. Only minor differences were found in the position of the intake target for the two phases, despite their different energetic requirements for migration as adults. When restricted to nutritionally imbalanced diets, caterpillars of both phases were less disposed to overeat protein on high-protein diets than carbohydrate on high-carbohydrate diets, relative to the self-composed intake target. However, in both cases gregarious larvae overingested the excess nutrient to a greater degree than did solitarious larvae. Furthermore, gregarious larvae showed higher nitrogen conversion efficiency on an extreme protein-limiting diet, and accumulated more lipid per amount of carbohydrate consumed on carbohydrate-deficient diets. These phase-associated nutritional differences are consistent with the life-history strategies of the two phases.