Joe Millward

• University of Surrey

Childhood growth and its sensitivity to dietary protein is reviewed within a Protein-Stat model of growth regulation. The coordination of growth of muscle and stature is a combination of genetic programming, and of two-way mechanical interactions involving the mechanotransduction of muscle growth through stretching by bone length growth, the core P...

The present paper reviews published literature on the relationship between dietary protein and bone health. It will include arguments both for and against the anabolic and catabolic effects of dietary protein on bone health. Adequate protein intake provides the amino acids used in building and maintaining bone tissue, as well as stimulating the act...

We undertook a systematic review and meta-analysis of published papers assessing dietary protein and bone health. We found little benefit of increasing protein intake for bone health in healthy adults but no indication of any detrimental effect, at least within the protein intakes of the populations studied. This systematic review and meta-analysis...

John Waterlow was an inspiring clinical and laboratory-based nutritional scientist, who was recognized as paterfamilias of a large, international and influential group of distinguished acolytes. His early work was characterized by study of the nature and clinical management of infantile malnutrition, notably as director of the MRC's Tropical Metabo...

The regulation of linear growth by nutritional and inflammatory influences is examined in terms of growth-plate endochondral ossification, in order to better understand stunted growth in children. Linear growth is controlled by complex genetic, physiological, and nutrient-sensitive endocrine/paracrine/autocrine mediated molecular signalling mechani...

Protein intake and bone health across the lifecycle: an updated systematic review and meta-analysis of the evidence - Volume 76 Issue OCE1 - D. Wynter, R. Manders, D.J. Torgerson, C.E. Hewitt, D.J. Millward, S.A. Lanham-New, A.L. Darling

The influence of dietary protein intake on bone health and fracture risk across the lifespan: a systematic review and meta-analysis - Volume 76 Issue OCE2 - A.L. Darling, D. Wynter, D.J. Torgerson, C.E. Hewitt, D.J. Millward, S.A. Lanham-New, R.J. Manders

Measured energy expenditure rather than intakes is used to derive dietary reference values for energy intakes. Population studies of energy expenditure with doubly labeled water, expressed as physical activity level (PAL) × basal metabolic rate (BMR), have indicated the distribution of PAL values so that recommendations can be calculated on the bas...

Individual and population allowances for dietary protein requirements derive from nitrogen balance studies. These are difficult to design, execute, and interpret, and current recommendations are controversial. Because of adaptation of the metabolic demand for amino acids to habitual protein intakes, the true minimum intake that will maintain a heal...

Sex differences in the ratio of fat mass (FM):fat-free mass (FFM) during weight change should differentially affect the extent of weight change during energy imbalance in men and women. In the present study, we determined FM and FFM contents by dual-energy X-ray absorptiometry and calculated the P-ratios (protein energy/total energy) of excess weig...

Obesity in the UK was assumed to have developed against a population decline in physical activity, with health messages focused on diet and exercise prevention strategies. Doubly-labelled water (DLW) studies of energy expenditure have indicated the alternative scenario that the increased obesity prevalence reflects excessive food energy intake with...

Leucine's wide-ranging metabolic influences have made it subject to special interest. It is abundant in the diet, especially in some milk and cereal proteins, in part due to its allocation of 6 codons in the genetic code, and individual dietary intakes range up to >250 mg ⋅ kg(-1) ⋅ d(-1). It influences many cell functions by various mechanisms, wh...

To describe the methodology behind the new UK Dietary Recommendations for Energy. Large interindividual variation in discretionary activity prevents prediction of energy expenditure, [total energy expenditure (TEE)], as a function of physical activity levels (PALs), [e.g. TEE = PAL ×  basal metabolic rate (BMR)] with the previously assumed accuracy...

The WHO/FAO/UNU (2007) report examines dietary protein and amino acid requirements for all age groups, protein requirements during pregnancy, lactation and catch-up growth in children, the implications of these requirements for developing countries and protein quality evaluation. Requirements were defined as the minimum dietary intake which satisfi...

The 1985 FAO/WHO/UNU protein report defined reference amino acid patterns for infants based on breast milk and for preschool children, schoolchildren and adults from age specific estimates of dietary indispensible amino acid requirements divided by the safe protein requirement for each age group. This report argued that the protein quality of a die...

Nutritional interventions that might influence sarcopenia, as indicated by literature reporting on sarcopenia per se as well as dynapenia and frailty, are reviewed in relation to potential physiological aetiological factors, i.e. inactivity, anabolic resistance, inflammation, acidosis and vitamin D deficiency. As sarcopenia occurs in physically act...

Legally-binding legislation is now in place to ensure major reductions in greenhouse gas emissions in the UK. Reductions in intakes of meat and dairy products, which account for approximately 40% of food-related emissions, are an inevitable policy option. The present paper assesses, as far as is possible, the risk to nutritional status of such a po...

There has been a resurgence of interest in the controversial relation between dietary protein and bone health. This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were elect...

To investigate the relative efficacy of four popular weight-loss programmes on plasma lipids and lipoproteins as measures of CVD risk. A multi-centred, randomised, controlled trial of four diets - Dr Atkins' New Diet Revolution, The Slim-Fast Plan, Weight Watchers Pure Points programme and Rosemary Conley's 'Eat yourself Slim' Diet and Fitness Plan...

Protein quality describes characteristics of a protein in relation to its ability to achieve defined metabolic actions. Traditionally, this has been discussed solely in the context of a protein's ability to provide specific patterns of amino acids to satisfy the demands for synthesis of protein as measured by animal growth or, in humans, nitrogen b...

Rate of Protein Turnover in Skeletal Muscle and Changes During Growth and Atrophy3-Methylhistidine Excretion Rates: A Cautionary NoteHormonal Regulation of Muscle Proteinturnover: Thyroid HormonesContractile Activity in Muscle and Protein TurnoverMuscle Proteinases Involved in Protein DegradationConclusions AcknowledgementsReferenceDiscussionRefere...

Obesity and type 2 diabetes are inextricably linked. It is therefore unfortunate that insulin, the ultimate treatment to improve glycaemic control in type 2 diabetes, is associated with significant weight gain. The aim of the present investigation was to ascertain whether a dietitian-led intensive lifestyle intervention could attenuate weight gain...

Dietary intake has been shown to influence acid-base balance in human subjects under tightly controlled conditions. However, the net effect of food groups on alkali/acid loading in population groups is unclear. The aims of the present study were to: (1) quantify estimates of daily net endogenous acid production (NEAP) (mEq/d) in a representative gr...

The aim of this presentation was to assess the impact of a ‘vegetarian diet’ on indices of skeletal integrity. Analyses of existing literature were assessed in relation to bone health for: lacto-ovo-vegetarian and vegan diets vs. omnivorous; predominantly meat diets; consumption of animal vs. vegetable protein; fruit and vegetable consumption. The...

Insulin resistance is associated with elevated plasma triacylglycerol, low HDL concentrations, elevated postprandial lipemia, and a predominance of small, dense LDLs (sdLDLs). It has been hypothesized that the dietary ratio of n-6 to n-3 (n-6:n-3) polyunsaturated fatty acids (PUFAs) may have favorable effects on these risk factors by increasing ins...

Elevated fibrinogen, activated factor XII (FXIIa), and factor VII coagulant activity (FVIIc) are associated with higher risk of fatal ischemic heart disease. This study tested the hypothesis that lowering the dietary ratio of n-6 to n-3 polyunsaturated fatty acids (n-6:n-3) would modify these risk factors in older men and women. The objective of th...

Background:Elevatedfibrinogen,activatedfactorXII(FXIIa),and factor VII coagulant activity (FVIIc) are associated with higher risk of fatal ischemic heart disease. This study tested the hypothesis that loweringthedietaryratioofn6ton3polyunsaturatedfattyacids (n6:n3) would modify these risk factors in older men and women. Objective: The objective of...

To compare the effectiveness of four commercial weight loss diets available to adults in the United Kingdom. Six month multicentre randomised unblinded controlled trial. Community based sample of otherwise healthy overweight and obese adults. Dr Atkins' new diet revolution, Slim-Fast plan, Weight Watchers pure points programme, and Rosemary Conley'...

The precise role that isoflavones play in the health-related effects of soy foods, and their potential for adverse effects are controversial. This may be due in part to a lack of basic knowledge regarding their bioavailability and metabolism, particularly as it relates to the soy source. To date, there is little information concerning possible diff...

We tested the hypothesis that dietary alpha-linolenic acid (ALA) can exert effects on markers of cardiovascular risk similar to that produced by its longer chain counterparts in fish-oil. A dietary intervention study was undertaken to examine the effects of an ALA-enriched diet in 57 men expressing an atherogenic lipoprotein phenotype (ALP). Subjec...

We studied the long-chain conversion of [U-¹³C]α-linolenic acid (ALA) and linoleic acid (LA) and responses of erythrocyte phospholipid composition to variation in the dietary ratios of 18:3n-3 (ALA) and 18:2n-6 (LA) for 12 weeks in 38 moderately hyperlipidemic men. Diets were enriched with either flaxseed oil (FXO; 17 g/day ALA, n = 21) or sunflowe...

We studied the long-chain conversion of [U-C-13](alpha-linolenic acid (ALA) and linoleic acid (ALA) and responses of erythrocyte phospholipid composition to variation in the dietary ratios of 18:3n-3 (ALA) and 18:2n-6 (LA) for 12 weeks in 38 moderately hyperlipidemic men. Diets were enriched with either flaxseed oil (FXO; 17 g/day ALA, n = 2 1) or...

The metabolic fate of salvaged urea-nitrogen was explored in normal adults who had consumed a diet that provided 36 g protein/day for 7 days. We hypothesised that the colonic microflora utilise nitrogen derived from urea salvage to synthesise lysine in functionally significant amounts for the host. Oral lactose-[(15)N(15)N]ureide is resistant to di...

It has long been known that dietary amino acid adequacy is markedly influenced by energy balance but in recent years the importance of this has been generally underestimated. Important practical issues include unintentional variation in energy intake and consequence energy balance that may be responsible for much of the apparent variability in prot...

Revised estimates of protein and amino acid requirements are under discussion by the Food and Agriculture Organization (FAO)/World Health Organizaion (WHO), and have been proposed in a recent report on Dietary Reference Intakes (DRIs) from the USA. The nature and magnitude of these requirements are not entirely resolved, and no consideration has be...

Urinary isoflavone excretion is used to monitor compliance and examine biological effects. The present study determined if there were alterations in urinary isoflavone excretion following the ingestion of different soya foods and if age and gender potentially modified profiles. Twenty premenopausal women, seventeen post-menopausal women and twenty...

The shortcomings of the metabolic implications of the current protein requirements model are reviewed, and an alternative model, validated with [1-(13)C]leucine balance results in human adults, is presented and evaluated in the context of defining protein requirements. The model identifies metabolic demands for amino acids as comprising a small fix...

Aspartame has been previously shown to increase satiety. This study aimed to investigate a possible role for the satiety hormones cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) in this effect. The effects of the constituents of aspartame, phenylalanine and aspartic acid, were also examined. Six subjects consumed an encapsulated preload c...

Protein, generally agreed to be the most satiating macronutrient, may differ in its effects on appetite depending on the protein source and variation in digestion and absorption. We investigated the effects of two milk protein types, casein and whey, on food intake and subjective ratings of hunger and fullness, and on postprandial metabolite and ga...

The cat (Felis silvestris catus) has a higher dietary protein requirement than omnivores and herbivores, thought to be due to metabolic inflexibility. An aspect of metabolic flexibility was examined with studies of whole-body protein turnover at two levels of dietary protein energy, moderate protein (MP; 20 %) and high protein (HP; 70 %), in five a...

We recently reported better wheat-protein utilization and a higher apparent lysine requirement than would be predicted, because of adaptive mechanisms of lysine conservation. However, such findings may be subject to the feeding protocol of frequent small meals. We used a [1-13C]leucine balance, large single-meal protocol to estimate the utilization...

The UK Food Standards Agency convened a group of expert scientists to review current research investigating whether n-3 polyunsaturated fatty acids (PUFA) from plant oils (alpha-linolenic acid; ALA) were as beneficial to cardiovascular health as the n-3 PUFA from the marine oils, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The works...

Complete excreta collection is a pre-requisite for several protocols in protein metabolism, and lack of confidence in achieving this may be increased when working with carnivores. Recovery of p-aminobenzoic acid (PABA) as a check for complete urine collection and chromic oxide for complete faeces collection were assessed in the cat. A single oral d...

Protein intakes vary widely but costs and benefits of such variation is a long standing unresolved issue. The wide range of reported values for the minimum protein intake for N equilibrium in adults, i.e. 0.39 to 1.09 g/kg is best explained by an Adaptive Metabolic Demands model in which metabolic demands include amino acid oxidation at a rate vary...

The effect of two levels of dietary protein energy, moderate (20%; MP) and high (70%; HP), on urea kinetics in eleven domestic cats was studied. After a 3-week prefeed, a single dose of [(15)N(15)N]urea was administered, and urine and faeces collected over the subsequent 5 d. For each 24 h period, total urea and enrichment of [(15)N(15)N]- and [(15...

To investigate whether appetite response to a high-protein test meal varies inversely with habitual protein intake, the satiating influence of dietary protein was investigated in 14 subjects. Subjects were divided into two groups on the basis of habitual protein intake: means of 1.0 g/kg/day (LP) and 1.4 g/kg/day (HP). Appetite was assessed in each...

There is considerable debate about the human lysine requirement and the consequent nutritional value of wheat protein. We used a novel [1-(13)C]leucine balance protocol to examine whether adaptive mechanisms to conserve lysine allow wheat to be utilized more efficiently than expected according to current estimates of lysine requirements and wheat u...

To explore the nutritional significance of urea hydrolysis for human subjects, male infants being treated for severe undernutrition were given oral doses of 10 mg [15N15N]urea every 3 h for 36 h, on admission, during rapid growth and after repletion with either moderate or generous intakes of protein. Urea hydrolysis was calculated from the 15N enr...

For protein, progress is slow in defining quantifiable indicators of adequacy other than balance and growth. As far as current requirements are concerned, only in the case of infants and children is there any case for revision, and this change is to lower values. Such intakes would appear to be safe when consumed as milk formula. In pregnancy, notw...

The case mortality for severe malnutrition in childhood remains high, but established best approaches to treatment are not used in practice. The energy and protein content of the diet at different stages of treatment appears important, but remains controversial. The effect on growth, urea kinetics and the urinary excretion of 5-L-oxoproline was com...

The adequacy of plant-based diets in developed and developing countries as sources of protein and amino acids for human subjects of all ages is examined. Protein quantity is shown not to be an issue. Digestibility is identified as a problem for some cereals (millet (Panicum miliaceum) and sorghum (Sorghum sp.)) and generally is poorly understood. D...

1. The variability between normal individuals in the efficiency of postprandial protein utilization (PPU), a determinant of the apparent protein requirement, was examined in relation to the relative responses of protein synthesis and proteolysis to protein feeding by means of [1–13C]leucine turnover and balance studies. 2. Twenty-five healthy adult...

In 1988, Millward and Rivers reappraised existing metabolic models for amino acid requirements. The metabolic demand for amino acids was reviewed in relation to both obligatory metabolic consumption and adaptive pathways of amino acid oxidation. The obligatory demand pattern was deemed unknowable from first principles except that the revel of one a...

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Plant proteins can differ from animal proteins in terms of digestibility, amino acid composition, the presence of antinutritional factors which influence digestibility and safety, and the presence of phytoprotectant factors which mediate disease protection. Nevertheless, plant proteins can provide all of human amino acid needs at all ages.

Current protein requirements for the elderly derive from 1985 FAO/WHO/UNU recommendations of no change with age in adults: i.e., 0.6 g/kg average and 0.75 g/kg safe allowance. Although concern has been expressed that protein requirements for the elderly may be greater, a review of nitrogen balance data, none of which are entirely satisfactory, indi...

The protein requirements of the elderly were investigated with [13C]leucine balance studies of metabolic demand, the efficiency of postprandial protein utilization (PPU) and the consequent apparent protein requirement. Ten elderly subjects aged 68-91 years (five men and five women) and ten young adult subjects aged 21-31 years (five men and five wo...

In work aimed at developing methodologies for validation of estimates of the dietary intake of free-living individuals, Bingham and colleagues have examined the use of urinary nitrogen (UN) excretion as an index of protein intake (Bingham & Cummings, 1985; Bingham, 1994; Bingham et al. 1995). The basis of this approach is that in subjects in N equi...

Current post-prandial studies of amino acid metabolism and utilization are consistent with a feeding mechanism mediated primarily by insulin and amino acids, with the balance between protein conservation and net deposition dependent on the amino acid supply [1-13C]leucine post-prandial kinetic tracer studies of leucine oxidation, non-oxidative disa...

Ten adult men were infused with L-[1-13C]leucine for 9 h commencing in the postabsorptive state (PA, 0-3 h), during the half-hourly feeding of low-protein meals (LP, protein = 2% calories, 3-6 h), and during feeding isoenergetic high-protein meals (HP, protein = 14% calories, 6-9 h). Leucine oxidation and turnover (protein synthesis and degradation...

1. We report here the extent to which changes in protein turnover contribute to the previously described inhibition of growth of rat tibial length and skeletal muscle mass in response to protein deficiency [1], energy restriction and corticosterone treatment [2]. Measurements of 35S uptake in vivo also enabled the qualitative pattern of changes in...

Six successful members of the British Women's Lightweight Rowing Team were assessed before and after two-month (1990) and four-month (1991) periods of weight-reduction controlled by reduced caloric intake, while engaged in their normal physical training. Fat free mass (FFM) was calculated from body weight (BW) by utilising total body potassium meas...

1. The influence of dietary energy restriction and corticosterone on long bone and muscle growth, and their interrelationships, was studied in rats fed a range of restricted amounts of diets containing increasing concentrations of protein, thus maintaining constant protein intakes. Tibial length and epiphyseal cartilage width were measured radiogra...

1. We report here studies of the interrelationship of bone and muscle growth in the rat and the regulatory role of dietary protein. Two experiments were undertaken. In experiment 1, growth inhibition was induced by ad libitum feeding of low protein diets containing 7%, 3.5% or 0.5% protein, with a control group fed a 20% protein diet. Measurements...

a3 Nutritional Research Unit, London School of Hygiene and Tropical Medicine, St Pancras Hospital, 4 St Pancras Way, London NW1 2PE

1. The diurnal changes in whole body protein turnover associated with the increasing fasting body nitrogen (N) losses and feeding gains with increasing protein intake were investigated in normal adults. [13C]Leucine, [2H5]phenylalanine and [2H2]tyrosine kinetics, were measured during an 8h primed, continuous infusion during the fasting and feeding...

1. The diurnal nature of nitrogen (N) homoeostasis was investigated in adults fed increasing protein intakes. N balance was estimated during a 48 h period of consecutive 12 h periods of feeding hourly meals and fasting, after 12 days of adaptation to diets containing 0.36 +0.01, 0.77 + 0.03, 1.59 +0.08 and 2.31 +0.65 g of protein day−1 kg−1. N loss...

1. The adaptation of the diurnal cycle of nitrogen (N) homoeostasis during a change in protein intake was investigated with diurnal measurements of N and leucine balance and turnover during a reduction from a high to a moderate protein intake in normal adults. 2. In experiment 1, during a 9 day period after a reduction from 1.82 to 0.77 g of protei...