Dennis Bier

• Baylor College of Medicine

Objective: To present an application of specification curve analysis - a novel analytic method that involves defining and implementing all plausible and valid analytic approaches for addressing a research question - to nutritional epidemiology. Data source: National Health and Nutrition Examination Survey (NHANES) 2007 to 2014 linked with National...

Background Beginning in 1977, the U.S. Government began formally issuing dietary advice, a main objective of which was to reduce and prevent the prevalence of obesity in the American population. Concurrently, the Harvard School of Public Health began conducting dietary intake surveys and collecting body mass index (BMI) (kg/m²) data on female nurse...

Purpose and methods This summary is based on a scientific symposium organized by the Mediterranean Diet Roundtable and the American Italian Food Coalition titled, ‘Positive Nutrition: shifting focus from nutrients to diet for a healthy lifestyle.’ It was held at the Embassy of Italy in Washington DC in September of 2022. The panel of experts discus...

The U.S. Dietary Guidelines for Americans is an enormously influential policy that has guided US nutrition programs since 1980. During these last forty years, some researchers have expressed concern that the guidelines are based on an insufficiently rigorous assessment of the scientific evidence, a view that was largely substantiated by a Congressi...

The NOVA classification of food items has become increasingly popular and is being used in several observational studies as well as in nutritional guidelines and recommendations. We propose that there is a need for this classification and its use in the formulation of public health policies to be critically discussed and re-appraised. The terms "pr...

To date, nutritional epidemiology has relied heavily on relatively weak methods including simple observational designs and substandard measurements. Despite low internal validity and other sources of bias, claims of causality are made commonly in this literature. Nutritional epidemiology investigations can be improved through greater scientific rig...

The last decade has seen nearly 20 papers reviewing the totality of the data on saturated fats and cardiovascular outcomes, which, altogether, have demonstrated a lack of rigorous evidence to support continued recommendations either to limit the consumption of saturated fatty acids or to replace them with polyunsaturated fatty acids. These papers w...

Phenylalanine and serine are amino acids used in dietary supplements and nutritional products consumed by healthy consumers; however, the safe level of phenylalanine or serine supplementation is unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral phenylalan...

Given the challenges with nutrition research, the Canadian Nutrition Society and Intertek Health Sciences Inc held an expert consultation in late 2019 to discuss the development and implementation of best practices for clinical trials on whole foods. Key challenges in the design, interpretation, and reporting of clinical efficacy studies on whole f...

Over the course of evolution, Mother Nature preserved the ability of humans to make every sugar they need for metabolic functions. Glucose is the almost exclusive fuel preferred by the human brain. Human infants are born with sweet taste receptors, sugars are a significant energy source in human milk, and mammals have a direct gut-to-brain sugar-se...

Based on research presented during the 10th Amino Acid Assessment Workshop, no observed adverse effect levels (NOAELs) for supplemental methionine at 46 mg/(kg·d) (∼3.2 g/d), for supplemental histidine at 8.0 g/d, and for supplemental lysine at 6.0 g/d have been proposed. These NOAELs are relevant to healthy adults and are applicable only to high-p...

The recommendation to limit dietary saturated fatty acid (SFA) intake has persisted despite mounting evidence to the contrary. Most recent meta-analyses of randomized trials and observational studies found no beneficial effects of reducing SFA intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against s...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Given the important role that nutritional science plays in global food and health policy, some of the key uncertainties in nutrition research that policy makers should take into consideration are outlined here.

Dairy has been described as everything from a superfood to a poison; yet, arguments, assumptions, and data justifying these labels are not always clear. We used an issue-based information system, “dialogue mapping™,” to summarize scientific points of a live panel discussion on the putative effects of dairy on cardiovascular diseases (CVD) from a da...

The practice of evidence-based nutrition involves using the best available nutrition evidence, together with clinical experience, to conscientiously work with patients' values and preferences to help them prevent (sometimes), resolve (sometimes), or cope with (often) problems related to their physical, mental, and social health. This article outlin...

Nearly 50 years ago, I set out to investigate the clinical problem of hypoglycemia in children with illnesses that limited their food intake. My goal was to gather accurate and precise measurable data. At the time, I wasn't interested in nutrition as a discipline defined in its more general or popular sense. To address the specific problem that int...

Dietary Reference Intakes (DRIs) are used in Canada and the United States in planning and assessing diets of apparently healthy individuals and population groups. The approaches used to establish DRIs on the basis of classical nutrient deficiencies and/or toxicities have worked well. However, it has proved to be more challenging to base DRI values...

On the basis of research presented during the 9th Amino Acid Assessment Workshop, a No Observed Adverse Effect Level (NOAEL) for diet-added arginine (added mostly in the form of dietary supplements) of 30 g/d and an upper limit of safe intake (ULSI) for diet-added tryptophan (added mostly in the form of dietary supplements) of 4.5 g/d have been pro...

Historically, the so-called "lipid hypothesis" has focused on the detrimental role of saturated fats per se in enhancing the risks of cardiovascular disease. Recently, a body of new information and systematic analyses of available data have questioned simple interpretation of the relationship of dietary saturated fats and of individual saturated fa...

Humans interact with food daily. Such repeated exposure creates a widespread, superficial familiarity with nutrition. Personal familiarity with nutrition from individual and cultural perspectives may give rise to beliefs about food not grounded in scientific evidence. In this summary of the session entitled “Unscientific Beliefs about Scientific To...

The real and important role of epidemiology was discussed, noting heretofore unknown associations that led to improved understanding of the cause and prevention of individual nutritional deficiencies. However, epidemiology has been less successful in linking individual nutrients to the cause of chronic diseases, such as cancer and cardiovascular di...

Proper nutrition offers one of the most effective and least costly ways to decrease the burden of many diseases and their associated risk factors , including obesity. Nutrition research holds the key to increasing our understanding of the causes of obesity and its related comorbid-ities and thus holds promise to markedly influence global health and...

Proper nutrition offers one of the most effective and least costly ways to decrease the burden of many diseases and their associated risk factors, including obesity. Nutrition research holds the key to increasing our understanding of the causes of obesity and its related comorbidities and thus holds promise to markedly influence global health and e...

Proper nutrition offers one of the most effective and least costly ways to decrease the burden of many diseases and their associated risk factors, including obesity. Nutrition research holds the key to increasing our understanding of the causes of obesity and its related comorbidities and thus holds promise to markedly influence global health and e...

Based on recent research, an upper limit of safe intake (ULSI) for leucine is proposed for healthy adults: 0.53 g/(kg⋅d). Because leucine has been used as a dietary supplement for many years in people practicing exercise and sport, further study with long-term exposure to leucine in this specific subpopulation should be performed to eventually adju...

The morning of the first day of the 8th Amino Acid Assessment Workshop was organized and co-sponsored by the International Council on Amino Acid Science (ICAAS) and the International Life Sciences Institute Research Foundation and was focused on the International Life Sciences Institute Research Foundation's approach to establishing upper limits of...

In the United States, the general standard for food safety is reasonable certainty of causing no harm under the intended conditions of use. In contrast to food safety policy in some other countries, the United States treats foods for infants and children no differently than foods for adults, other than requiring additional standards for infant form...

Truly impactful innovation can only be recognized in retrospect. Moreover, almost by definition, developing algorithmic paths on roadmaps for innovation are likely to be unsuccessful because innovators do not generally follow established routes. Nonetheless, environments can be established within Departments of Pediatrics that promote innovating th...

Close, tightly orchestrated interactions between the intestinal epithelium and the mucosa-associated immune system are critical for normal intestinal absorptive and immunological functions. Recent data indicate that commensal intestinal microbiota represents a major modulator of intestinal homeostasis. This review analyzes the process of intestinal...

Given the increase in the incidence of insulin resistance, obesity, and type 2 diabetes in children and adolescents, it would be of paramount importance to assess quantitative indices of insulin secretion and action during a physiological perturbation, such as a meal or an oral glucose-tolerance test (OGTT). A minimal model method is proposed to me...

For more than a century, experts have produced dietary guidance aimed at increasing consumption of certain nutrients and food groups, yet compliance is poor. As the planning stage for the Dietary Guidelines begins and it is clear that dietary change has been difficult to accomplish, perhaps, the right question to ask is "Which dietary changes are m...

Birth and adaptation to extrauterine life involve major shifts in the protein and energy metabolism of the human newborn. These include a shift from a state of continuous supply of nutrients including amino acids from the mother to cyclic periodic oral intake, a change in the redox state of organs, thermogenesis, and a significant change in the mob...

There is virtually no information on the metabolic impact of dietary fructose intake in adolescents despite their high fructose consumption, particularly via sweetened beverages. To determine the short-term metabolic effects of dietary fructose intake in obese adolescents. Six volunteers (3 M/3 F; 15.2 +/- 0.5 yr; 35 +/- 2 kg/m2; 39 +/- 2% body fat...

The prevention and treatment of childhood obesity have proven to be extremely difficult problems. Since the equation for maintaining energy balance is an extremely simple one, having only two terms, 'energy in' and 'energy out', the difficulties encountered in its application for obesity management are not immediately obvious. Among the problems th...

Compared to other periods of life, infancy is a period of rapid growth, but the relative relationships among rates of linear growth, weight accretion and brain growth vary greatly during the first years of life. Additionally, while the energy requirements for body tissue deposition as a fraction of daily energy needs decrease dramatically during in...

Compared to other periods of life, infancy is a period of rapid growth, but the relative relationships among rates of linear growth, weight accretion and brain growth vary greatly during the first years of life. Additionally, while the energy requirements for body tissue deposition as a fraction of daily energy needs decrease dramatically during in...

Developmental origins of health and disease (DOHaD) focuses on the earliest stages of human development, and provides a novel paradigm to complement other strategies for lifelong prevention of common chronic health conditions. The 3 International Congress on DOHaD, held in 2005, retained the most popular features from the first two biannual Congres...

The concept of the nutritional phenotype is proposed as a defined and integrated set of genetic, proteomic, metabolomic, functional, and behavioral factors that, when measured, form the basis for assessment of human nutritional status. The nutritional phenotype integrates the effects of diet on disease/wellness and is the quantitative indication of...

Adolescent obesity is a serious public health concern. The aim of the study was to determine whether obese adolescents can adapt metabolically to changes in dietary macronutrient intake. Using a random cross-over design, 13 healthy obese volunteers (six boys and seven girls; age, 14.7 +/- 0.3 yr; body mass index, 34 +/- 1 kg/m2; body fat, 42 +/- 1%...

To evaluate the efficacy of antioxidant supplementation in preventing kwashiorkor in a population of Malawian children at high risk of developing kwashiorkor. Prospective, double blind, placebo controlled trial randomised by household. 8 villages in rural southern Malawi. 2372 children in 2156 households aged 1-4 years were enrolled; 2332 completed...

The concept of the nutritional phenotype is proposed as a defined and integrated set of genetic, proteomic, metabolomic, functional, and behavioral factors that, when measured, form the basis for assessment of human nutritional status. The nutritional phenotype integrates the effects of diet on disease/wellness and is the quantitative indication of...

In 1989, reports suggested that the fetal environment, as reflected in birth size, was related to the risk of noncommunicable diseases in adult life. This association was first described for coronary heart disease but rapidly extended to include type 2 diabetes, osteoporosis, and metabolic and endocrine homeostasis. This led to the development of t...

Tracer kinetic studies of amino acid metabolism during periods of high amino acid intake should allow insights into adaptive or maladaptive regulatory mechanisms controlling amino acid catabolic or disposal events before clinically evident effects. The principles of amino acid tracer kinetics have been well defined, but their application to establi...

Tracer kinetic studies of amino acid metabolism during periods of high amino acid intake should allow insights into adaptive or maladaptive regulatory mechanisms controlling amino acid catabolic or disposal events before clinically evident effects. The principles of amino acid tracer kinetics have been well defined, but their application to establi...

Difficulty adapting to high-fat (HF) and high carbohydrate (HC) diets may predispose children to obesity and diabetes. We tested the hypothesis that children have metabolic flexibility to adapt to HF and HC diets. In protocol 1, 12 children aged 6-9 y and 12 adolescents aged 13-16 y were randomly assigned in a crossover design to consume low-fat (L...

Effects of carbohydrate, fat, and fructose intake on substrate and hormone concentrations, glucose production, gluconeogenesis, and insulin sensitivity were determined in healthy, nonobese prepubertal children (n = 12) and adolescents (n = 24) using a cross-over design. In one group (12 prepubertal children and 12 adolescents), subjects were studie...

Many children with human immunodeficiency virus-1 (HIV-1) have chronic problems with growth and nutrition, yet limited information is available to identify infected children at high risk for growth abnormalities. Using data from the prospective, multicenter P2C2 HIV study, we evaluated the relationships between maternal and infant clinical and labo...

A large number of studies in recent years have described protein and nitrogen metabolism in the neonate. However, the majority of these data are difficult to interpret because of a number of confounding variables, particularly in very low birth weight (VLBW) infants. In contrast, application of state-of-the-art tracer isotopic and molecular biology...

The prevalence of overweight and obese children has doubled, and the incidence of type 2 diabetes in children (0-19 y) has increased 4-fold during the past several decades. As a result we can anticipate an increased number of metabolic studies in children. There are few data on measures of glucose metabolism in normal children, and virtually none r...

The classic (hereafter cold) and the labeled (hereafter hot) minimal models are powerful tools to investigate glucose metabolism. The cold model provides, from intravenous glucose tolerance test (IVGTT) data, indexes of glucose effectiveness (SG) and insulin sensitivity (SI) that measure the effect of glucose and insulin, respectively, to enhance g...

151 Background/Aim: The increasing incidence of obesity and NIDDM has lead to recommendations to reduce the dietary fat intake. As a consequence, to maintain energy balance, the CHO intake must be increased. This study was undertaken to determine if a high CHO/low fat diet adversely affected parameters of glucose metabolism in adolescents. Subjects...

Very low birth weight (VLBW) infants are dependent on total parenteral nutrition (TPN) to prevent hypoglycemia and provide a sufficient energy intake. However, diminished tolerance for parenteral glucose delivered at high rates frequently provokes hyperglycemia. We hypothesized that when their glucose supply is reduced to prevent hyperglycemia, VLB...

Recently, a new method, based on a two-compartment minimal model and deconvolution [A. Caumo and C. Cobelli. Am. J. Physiol 264 (Endocrinol. Metab. 37): E829-E841, 1993; P. Vicini, G. Sparacino, A. Caumo, and C. Cobelli. Comput. Meth. Prog. Biomed. 52: 147-156, 1997], has been proposed to estimate endogenous glucose production (EGP) from labeled in...

184 Background: VLBW infants are dependent on parenteral nutrition(TPN) to prevent hypoglycemia and energy deficiency. However, diminished tolerance for parenteral glucose may provoke hyperglycemia. Thus, information on the gluconeogenic substrate role of amino acids and lipids is crucial to optimize the composition of TPN. Aim: Estimate gluconeoge...

185 Background: Because glucose production (GPR) in children is greater than in adolescents, we hypothesized that the rate of gluconeogenesis(GNG) and the fraction of GPR derived from GNG would also be increased in children. Aim: 1. Measure GPR and GNG in children and adolescents, and 2. Determine the reproducibility of these measures when activity...

Metabolic research in the pregnant woman and human neonate is generally limited by several basic ethical constraints. First, the studies must be noninvasive or minimally so, except in unusual circumstances. Second, if blood or tissue samples are needed, they should be invariably small, particularly those samples obtained from the fetus or very low...

In order to follow the movement and quantify the metabolic fates of biologically important molecules in vivo, both tracers and kinetic modeling are required. For the study of intermediary metabolism in children, stable isotopically labeled substrates satisfy both the analytical and ethical requirements for tracer use in children. Stable isotope tra...

There is evidence that glutamine may act as a regulator of protein, free fatty acid, and glycogen metabolism. To test the hypothesis that glutamine may act as a physiological regulator of gluconeogenesis, we infused 16 normal postabsorptive volunteers with glutamine at a rate (11.4 micromol kg(-1) x min(-1)) estimated to approximate its appearance...

The purpose of this study was to determine whether GH treatment of cystic fibrosis (CF) patients can result in an anabolic effect, i.e., increased weight gain, improved growth rate, nitrogen retention, and improved pulmonary function. Nine prepubertal endocrinologically normal CF patients (3 girls, 6 boys; chronological age (CA) 5.5-9.8 years, and...

Gluconeogenesis is increased in NIDDM. We therefore examined the metabolism of glutamine and alanine, the most important gluconeogenic amino acids, in 14 postabsorptive NIDDM subjects and 18 nondiabetic volunteers using a combination of isotopic ([6-3H]glucose (20 microCi, 0.2 microCi/min), [U-14C]glutamine (20 microCi, 0.2 microCi/min), [3-13C]ala...

Insulin resistance for glucose metabolism in skeletal muscle is a key feature in NIDDM. The quantitative role of the cellular effectors of glucose metabolism in determining this insulin resistance is still imperfectly known. We assessed transmembrane glucose transport and intracellular glucose phosphorylation in vivo in skeletal muscle in nonobese...

We studied five healthy subjects with perfused forearm and euglycemic clamp techniques in combination with a three-tracer (D-[12C]mannitol, not transportable; 3-O-[14C]methyl-D-glucose, transportable but not metabolizable; D-[3-3H]glucose, transportable and metabolizable) intra-arterial pulse injection to assess transmembrane transport and intracel...

To assess the effects of 16 weeks of heavy resistance exercise training (RE) on insulin sensitivity and secretion in healthy older men aged 64 to 75 years (N = 15), stable-label ([6,6,2H2]glucose) intravenous glucose tolerance tests (IVGTTs) were performed before and 7 days after the last bout of exercise. Glucose disappearance rate (Rd) and an ind...

Muscle weakness and wasting in myotonic dystrophy (MyD) are believed to be due to a decrease in muscle protein synthesis, secondary to insulin resistance. A 4-month, randomized, double blind, placebo-controlled trial was undertaken to assess whether recombinant human insulin-like growth factor I (rhIGF-I) may overcome the insulin resistance. Patien...

Enrichment in hippurate has been measured to indicate precursor enrichment during glycine tracer infusion studies to estimate fractional synthetic rates of individual hepatic export proteins. However, hippurate tends to overestimate precursor enrichment. Since glycine is rapidly converted to serine by liver cells, we compared tracer enrichment in h...

To evaluate transfer of carbon between plasma glucose and plasma alanine (glucose-alanine cycle) and lactate (Cori cycle), to assess the contribution of skeletal muscle to these cycles, and to determine whether a glucose-glutamine cycle exists in postabsorptive humans, we infused 11 normal overnight-fasted volunteers with [2-3H]glucose, [6-14C]gluc...

To assess the production of the nonessential amino acid tyrosine in preterm infants, we estimated the activity of phenylalanine hydroxylase (PAH) in three groups of infants by measuring the conversion of phenylalanine to tyrosine, using a model based on a primed constant 200-min intravenous infusion of [2H5]phenylalanine. We determined the isotopic...

Nineteen malnourished chronic peritoneal dialysis patients who were ingesting a low protein intake underwent metabolic balance studies to test whether a dialysate that contained amino acids would improve their protein nutrition. Patients lived in the hospital for 35 days while they ate a constant diet and underwent their usual regimen of continuous...

The purpose of this study was to determine whether growth hormone (GH) administration enhances the muscle protein anabolism associated with heavy-resistance exercise training in older men. Twenty-three healthy, sedentary men (67 +/- 1 yr) with low serum insulin-like growth factor I levels followed a 16-wk progressive resistance exercise program (75...