D. Joe Millward

Long-chain conversion of [13C]linoleic acid and α-linolenic acid in response to marked changes in their dietary intake in men

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 sunflower oil (SO; 17 g/day LA, n = 17). The FXO diet induced increases in phospholipid ALA (>3-fold), 20:5n-3 [eicosapentaenoic acid (EPA), >2-fold], and 22:5n-3 [docosapentaenoic acid (DPA), 50%] but no change in 22:6n-3 [docosahexanoic acid (DHA)], LA, or 20:4n-6 [arachidonic acid (AA)]. The increases in EPA and DPA but not DHA were similar to those in subjects given the SO diet enriched with 3 g of EPA plus DHA from fish oil (n = 19). The SO diet induced a small increase in LA but no change in AA. Long-chain conversion of [U-13C]ALA and [U-13C]LA, calculated from peak plasma 13C concentrations after simple modeling for tracer dilution in subsets from the FXO (n = 6) and SO (n = 5) diets, was similar but low for the two tracers (i.e., AA, 0.2%; EPA, 0.3%; and DPA, 0.02%) and varied directly with precursor concentrations and inversely with concentrations of fatty acids of the alternative series. [13C]DHA formation was very low (<0.01%) with no dietary influences.

Dietary protein and bone health: a systematic review and meta-analysis

BACKGROUND There has been a resurgence of interest in the controversial relation between dietary protein and bone health. OBJECTIVE This article reports on the first systematic review and meta-analysis of the relation between protein and bone health in healthy human adults. DESIGN The MEDLINE (January 1966 to September 2007) and EMBASE (1974 to July 2008) databases were electronically searched for all relevant studies of healthy adults; studies of calcium excretion or calcium balance were excluded. RESULTS In cross-sectional surveys, all pooled r values for the relation between protein intake and bone mineral density (BMD) or bone mineral content at the main clinically relevant sites were significant and positive; protein intake explained 1-2% of BMD. A meta-analysis of randomized placebo-controlled trials indicated a significant positive influence of all protein supplementation on lumbar spine BMD but showed no association with relative risk of hip fractures. No significant effects were identified for soy protein or milk basic protein on lumbar spine BMD. CONCLUSIONS A small positive effect of protein supplementation on lumbar spine BMD in randomized placebo-controlled trials supports the positive association between protein intake and bone health found in cross-sectional surveys. However, these results were not supported by cohort study findings for hip fracture risk. Any effects found were small and had 95% CIs that were close to zero. Therefore, there is a small benefit of protein on bone health, but the benefit may not necessarily translate into reduced fracture risk in the long term.

The nutritional value of plant-based diets in relation to human amino acid and protein requirements

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. Direct measurements of biological value in children are reviewed and scoring is considered. Various existing requirement values for amino acids and especially lysine are reviewed, and it is concluded that stable-isotope studies do not yet provide adequate alternative values of N balance data, which for lysine are robust after recalculation and adjustment. A new maintenance requirement pattern is developed, with higher values than those of Food and Agriculture Organization/World Health Organization/United Nations University (1985) but lower values than the Massachusetts Institute of Technology pattern (Young et al. 1989). Calculations of age-related amino acid requirements are based on most recent estimates of human growth and maintenance protein requirements, a tissue amino acid pattern and the new maintenance amino acid pattern. These values appear valid when used to score plant proteins, since they indicate values similar to or less than the biological value measured directly in young children. When used to score plant-based diets in India, no marked deficiencies are identified. All regions score > 1 for adults, whilst for children scores range from > 1, (Tamil Nadhu) from 6 months of age to 0.78 (West Bengal), rising to 0.9 in the 2-5 year old, consistent with reports that high-lysine maize supports similar weight and height growth to that of casein. Inadequate amino acid supply is not an issue with most cereal-based diets.

Plenary Lecture 3 Food and the planet: nutritional dilemmas of greenhouse gas emission reductions through reduced intakes of meat and dairy foods

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 policy in the context of the part played by these foods in overall health and well-being and their contribution to nutritional status for the major nutrients that they supply. Although meat may contribute to saturated fat intakes and a higher BMI, moderate meat consumption within generally-healthy population groups has no measurable influence on morbidity or mortality. However, high consumption of red and processed meat has been associated with increased risk of colo-rectal cancer and recent advice is to reduce intakes to a maximum of 70 g/d. Such reductions in meat and haem-Fe intake are unlikely to influence Fe status in functional terms. However, overall protein intakes would probably fall, with the potential for intakes to be less than current requirements for the elderly. Whether it is detrimental to health is uncertain and controversial. Zn intakes are also likely to fall, raising questions about child growth that are currently unanswerable. Milk and dairy products, currently specifically recommended for young children and pregnant women, provide 30-40% of dietary Ca, iodine, vitamin B12 and riboflavin. Population groups with low milk intakes generally show low intakes and poor status for each of these nutrients. Taken together it would appear that the reductions in meat and dairy foods, which are necessary to limit environmental damage, do pose serious nutritional challenges for some key nutrients. These challenges can be met, however, by improved public health advice on alternative dietary sources and by increasing food fortification.

A protein-stat mechanism for regulation of growth and maintenance of the lean body mass.

I N T R O D U C T I O N A N D N A T U R E O F T H E PROBLEM DIETARY P R O T E I N A N D G R O W T H C O N T R O L MECHANISMS . . G E N E T I C D E T E R M I N A T I O N . . F U N C T I O N A L D E M A N D . . N U T R I T I O N : PERMISSIVE A N D A C T I V E I N F L U E N C E S . . DIETARY P R O T E I N A N D R E G U L A T I O N O F L I N E A R G R O W T H . C E L L U L A R M E C H A N I S M S OF L I N E A R B O N E G R O W T H R E G U L A T I O N .

Metabolic Demands for Amino Acids and the Human Dietary Requirement: Millward and Rivers (1988) Revisited

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 level of one amino acid would be similar to its concentration in an amount of tissue protein equivalent to the obligatory nitrogen loss. The adaptive demand pattern was predicted to vary in relation to the amount and the periodicity of food protein intake that influenced the amplitude of the diurnal cycle of gains and losses. A regulatory influence of protein intake on anabolism, the anabolic drive, was identified in animal studies; benefit appeared to derive from intakes in excess of the minimum for balance, which could facilitate definition of an optimal requirement. The inherent and design-related limitations of both nitrogen and stable isotope balance studies of requirement were recognized as a major problem in identifying secure values for indispensable amino acid requirements. A decade of research of increasing methodological sophistication has generated much new information, confirming the adaptive diurnal model of balance regulation and allowing development of the anabolic drive into a general protein-stat theory for coordinated control of growth and maintenance of the lean body mass. However, notwithstanding several new estimates of amino acid requirement values, definition of a widely accepted human amino acid requirement pattern remains unresolved. Although a case can be made for an adjusted 1985 FAO adult requirement pattern being a reasonable estimate of the obligatory indispensable amino acid requirements for human maintenance, the problems posed by adaptation, methodological inadequacies and lack of independent measures of adequacy mean that assessment of the adequacy of the human diet to satisfy amino acid needs remains inherently difficult.

Nutrition and sarcopenia: evidence for an interaction.

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 active and presumably well-nourished populations, it is argued that a simple nutritional aetiology is unlikely and unequivocal evidence for any nutritional influence is extremely limited. Dietary protein is probably the most widely researched nutrient but only for frailty is there one study showing evidence of an aetiological influence and most intervention studies with protein or amino acids have proved ineffective with only a very few exceptions. Fish oil has been shown to attenuate anabolic resistance of muscle protein synthesis in one study. There is limited evidence for a protective influence of antioxidants and inducers of phase 2 proteins on sarcopenia, dynapenia and anabolic resistance in human and animal studies. Also fruit and vegetables may protect against acidosis-induced sarcopenia through their provision of dietary potassium. While severe vitamin D deficiency is associated with dynapenia and sarcopenia, the evidence for a beneficial influence of increasing vitamin D status above the severe deficiency level is limited and controversial, especially in men. On this basis there is insufficient evidence for any more specific nutritional advice than that contained in the general healthy lifestyle-healthy diet message: i.e. avoiding inactivity and low intakes of food energy and nutrients and maintain an active lifestyle with a diet providing a rich supply of fruit and vegetables and frequent oily fish.

Post-prandial protein metabolism

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 disappearance and endogenous appearance allow study of the regulation of whole-body amino acid oxidation, protein synthesis and proteolysis. On the basis of these studies it appears that for leucine oxidation, the main determinant of the efficiency of protein utilization, the overriding regulatory influence is substrate availability rather than insulin. Such substrate sensitivity is manifest throughout the physiological range of insulin down to the lowest insulin levels observed suggesting that a basal insulin need is not an important part of regulation of this important catabolic pathway. The key protein turnover response is an inhibition of proteolysis sufficient to limit any increases in amino acid levels thus limiting any increase in amino acid oxidation. It appears that the influences of amino acids and insulin on proteolysis are separate and additive and may both be receptor mediated so that extracellular amino acid levels can regulate intracellular levels. It is likely that protein synthesis is regulated by intracellular amino acid levels but post-prandial stimulation through increases in amino acid levels appears to be unhelpful because of parallel increases in amino acid oxidation. Evidence for any influence of insulin on protein synthesis has yet to be unequivocally identified.

Estimates of daily net endogenous acid production in the elderly UK population : analysis of the National Diet and Nutrition Survey (NDNS) of British adults aged 65 years and over

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 group of British elderly aged 65 years and older; (2) compare and characterise NEAP by specific nutrients and food groups likely to influence dietary acid loading; (3) determine whether geographical location influenced NEAP. The National Diet and Nutrition Survey dataset, consisting of a 4 d weighed record and anthropometric data, was used to estimate dietary acidity. Dietary under-reporters were excluded by analysing only subjects with energy intakes >/= 1.2 x BMR. NEAP was estimated as the dietary potential renal acid load+organic acid excretion, the latter as a multiple of estimated body surface area. NEAP was lower in women compared with men (P < 0.001), and lower than values reported in a Swedish elderly cohort. Lower dietary acidity was significantly associated with higher consumption of fruit and potatoes and lower consumption of meat, bread and eggs (P < 0.02 to P < 0.001). Lower intakes of fish and cheese were associated with lower NEAP in men only (P < 0.01 to P < 0.001). There were regional differences for NEAP, with higher intakes in Scotland/Northern regions compared with Central/South-Western and London/South-Eastern regions (P = 0.01). These data provide an insight into the acid-generating potential of the diet in the British elderly population, which may have important consequences in this vulnerable group.

Identifying recommended dietary allowances for protein and amino acids: a critique of the 2007 WHO/FAO/UNU report

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 satisfies the metabolic demand and achieves nitrogen equilibrium and maintenance of the body protein mass, plus the needs for growth in children and pregnancy and lactation in healthy women. Insufficient evidence was identified to enable recommendations for specific health outcomes. A meta analysis of nitrogen balance studies identifies protein requirements for adults 10 % higher than previous values with no influence of gender or age, consistent with a subsequently published comprehensive study. A new factorial model for infants and children, validated on the basis of the adequacy of breast milk protein intakes and involving a lower maintenance requirement value, no provision for saltatory growth and new estimates of protein deposition identifies lower protein requirements than in previous reports. Higher values for adult amino acid requirements, derived from a re-evaluation of nitrogen balance studies and new stable isotope studies, identify some cereal-based diets as being inadequate for lysine. The main outstanding issues relate to the biological implausibility of the very low efficiencies of protein utilisation used in the factorial models for protein requirements for all population groups especially pregnancy when requirements may be overestimated. Also considerable uncertainty remains about the design and interpretation of most of the studies used to identify amino acid requirement values.