Priority nutrients to address malnutrition and diet-related diseases in Australia and New Zealand.

Background: The double burden of malnutrition and diet-related disease has been attributed to diets high in ultra-processed and discretionary foods, with increased sugars, saturated fats, and sodium, and insufficient dietary fibre. There is a limited understanding of the role of other macronutrients and micronutrients. Objective: Determine the highest priority nutrients to address both malnutrition and diet-related disease in Australia and New Zealand, for each demographic group and the total population. Methods: A novel four-step methodological approach was undertaken to identify: 1. Demographic (age-sex) groups; 2. Health priorities; 3. Potential nutrients based on inadequacy, increased requirements, and health priority association; and 4. Priority nutrients. Nutrient intake data was obtained from the most recent Australian and New Zealand nutrition surveys. Health priorities were based on national statistical data and expert consultation. High-level scientific literature (systematic reviews) was scoped for associations with health priorities and the suitability of recommended intakes. A quantitative scoring matrix was developed and used to determine the highest priority nutrients, with scoring over three domains: extent of inadequacy; consensus for increased requirements; and degree of association with health priorities. Results: Nutritional inadequacies were common, with 22 of 31 essential nutrients consumed below recommended levels. Nine priority nutrients were identified across the demographic groups, with each demographic group characterised by a specific subset of these. Six nutrients were highest priority within the total population: vitamin D, calcium, omega-3 fatty acids, magnesium, folate, dietary fibre. Conclusion: The extent of nutritional inadequacies in Australia and New Zealand is high, both within each demographic group and the entire population, relative to both recommended intakes and key health outcomes. The methodology can be applied to other countries and globally. Findings make a significant contribution to understanding the nutrients to prioritise in future-proofing the health of the Australian and New Zealand populations. Guidelines and policies can target priority nutrients to address the malnutrition and diet-related disease double burden.

Nutrient Dense, Low-Cost Foods Can Improve the Affordability and Quality of the New Zealand Diet-A Substitution Modeling Study.

The high prevalence of non-communicable disease in New Zealand (NZ) is driven in part by unhealthy diet selections, with food costs contributing to an increased risk for vulnerable population groups. This study aimed to: (i) identify the nutrient density-to-cost ratio of NZ foods; (ii) model the impact of substituting foods with a lower nutrient density-to-cost ratio with those with a higher nutrient density-to-cost ratio on diet quality and affordability in representative NZ population samples for low and medium socioeconomic status (SES) households by ethnicity; and (iii) evaluate food processing level. Foods were categorized, coded for processing level and discretionary status, analyzed for nutrient density and cost, and ranked by nutrient density-to-cost ratio. The top quartile of nutrient dense, low-cost foods were 56% unprocessed (vegetables, fruit, porridge, pasta, rice, nuts/seeds), 31% ultra-processed (vegetable dishes, fortified bread, breakfast cereals unfortified <15 g sugars/100 g and fortified 15-30 g sugars/100 g), 6% processed (fruit juice), and 6% culinary processed (oils). Using substitution modeling, diet quality improved by 59% and 71% for adults and children, respectively, and affordability increased by 20-24%, depending on ethnicity and SES. The NZ diet can be made healthier and more affordable when nutritious, low-cost foods are selected. Processing levels in the healthier, modeled diet suggest that some non-discretionary ultra-processed foods may provide a valuable source of low-cost nutrition for food insecure populations.

Endogenous Amino Acid Losses from the Gastrointestinal Tract of the Adult Human-A Quantitative Model.

Background: The loss of endogenous (nondietary) amino acids (AAs) from the gastrointestinal tract (GIT) is an important component underlying the adult human dietary requirement for protein and essential AAs (EAAs). Although data with regard to endogenous AA losses to the end of the small intestine have been published, to our knowledge there are no direct measures of colonic endogenous AA losses. Objective: The objective was to derive quantitative estimates for daily endogenous protein and EAAs lost from the colon of the adult human. Methods: A factorial model was developed for the prediction of endogenous AA losses across the adult human GIT. Estimates of AAs entering the upper GIT lumen were combined with relative protein synthesis rates in the colon to predict colonic AA losses. The AA composition of human colonic endogenous protein was calculated by estimating the relative contributions of epithelial cell protein and mucin protein on the basis of published data for cell shedding in the pig small intestine, small intestinal protein synthesis rates in pigs and humans, and human upper and lower GIT surface areas. Colonic AA losses were summed with empirical estimates of ileal AA losses in humans to estimate total daily GIT endogenous AA losses. Results: Colonic AA loss was estimated to total 3.5 g/d in the adult male human, comprising 33% of total GIT endogenous AA loss (10.2 g/d). GIT essential AA losses accounted for 25-97% of the current recommended daily AA requirement for adult humans. For threonine, colonic losses were 54% of total GIT threonine losses, which were 97% of the current recommended daily threonine requirement. Conclusions: Colonic endogenous AA losses represent a significant fraction of total GIT endogenous AA losses. The requirement of the GIT for EAAs to replace AAs lost via the gut lumen comprises a substantial proportion of the Recommended Daily Intake of AAs.

The C313Y Piedmontese mutation decreases myostatin covalent dimerisation and stability.

BACKGROUND: Myostatin is a key negative regulator of muscle growth and development, whose activity has important implications for the treatment of muscle wastage disorders. Piedmontese cattle display a double-muscled phenotype associated with the expression of C313Y mutant myostatin. In vivo, C313Y myostatin is proteolytically processed, exported and circulated extracellularly but fails to correctly regulate muscle growth. The C313Y mutation removes the C313-containing disulphide bond, an integral part of the characteristic TGF-ß cystine-knot structural motif. RESULTS: Here we present in vitro analysis of the structure and stability of the C313Y myostatin protein that reveals significantly decreased covalent dimerisation for C313Y myostatin accompanied by a loss of structural stability compared to wild type. The C313Y myostatin growth factor, processed from full length precursor protein, fails to inhibit C2C12 myoblast proliferation in contrast to wild type myostatin. Although structural modeling shows the substitution of tyrosine causes structural perturbation, biochemical analysis of additional disulphide mutants, C313A and C374A, indicates that an intact cystine-knot motif is a major determinant in myostatin growth factor stability and covalent dimerisation. CONCLUSIONS: This research shows that the cystine-knot structure is important for myostatin dimerisation and stability, and that disruption of this structural motif perturbs myostatin signaling.

Cytotoxic aggregation and amyloid formation by the myostatin precursor protein.

Myostatin, a negative regulator of muscle growth, has been implicated in sporadic inclusion body myositis (sIBM). sIBM is the most common age-related muscle-wastage disease with a pathogenesis similar to that of amyloid disorders such as Alzheimer's and Parkinson's diseases. Myostatin precursor protein (MstnPP) has been shown to associate with large molecular weight filamentous inclusions containing the Alzheimer's amyloid beta peptide in sIBM tissue, and MstnPP is upregulated following ER stress. The mechanism for how MstnPP contributes to disease pathogenesis is unknown. Here, we show for the first time that MstnPP is capable of forming amyloid fibrils in vitro. When MstnPP-containing Escherichia coli inclusion bodies are refolded and purified, a proportion of MstnPP spontaneously misfolds into amyloid-like aggregates as characterised by electron microscopy and binding of the amyloid-specific dye thioflavin T. When subjected to a slightly acidic pH and elevated temperature, the aggregates form straight and unbranched amyloid fibrils 15 nm in diameter and also exhibit higher order amyloid structures. Circular dichroism spectroscopy reveals that the amyloid fibrils are dominated by beta-sheet and that their formation occurs via a conformational change that occurs at a physiologically relevant temperature. Importantly, MstnPP aggregates and protofibrils have a negative effect on the viability of myoblasts. These novel results show that the myostatin precursor protein is capable of forming amyloid structures in vitro with implications for a role in sIBM pathogenesis.