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D J Millward

Publications and source records attributed to D J Millward.

At least 37 records · Page 2Linked to original sources
PubMed1997

Protein requirements and ageing: metabolic demand and efficiency of utilization.

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 women) were infused with L-[1-13C]leucine for 9 h commencing in the postabsorptive state (0-3 h), continuing during the half-hourly feeding of low-protein meals (LP; protein 3% energy, 3-6 h), and during similar feeding of isoenergetic higher protein meals (HP; protein 15% energy, 6-9 h). Leucine oxidation and balance were determined from plasma [1-13C]-alpha-ketoisocaproate enrichment and expired 13CO2 excretion measured during the 3rd hour of each 3 h period. The protein intake during the HP phase was similar to the habitual intake estimated in the subjects from 24 h urinary N excretion. Metabolic demand was defined as equal to twice the body-protein equivalent of measured postabsorptive leucine oxidation. The efficiency of PPU was calculated from the increased leucine oxidation observed during feeding, and the apparent protein requirement was defined as metabolic demand/PPU and calculated in relation to both body weight (BW) and fat-free mass (FFM) determined by densitometry or bioimpedance. Metabolic demand in the young adults was 0.83 g protein/kg per d; in both elderly groups it was 36% lower when expressed per kg BW and 30% lower when expressed per kg FFM. The apparent protein requirement calculated from metabolic demand and PPU was 0.99 g protein/kg per d in the young adults and this was also lower in the elderly, although this was only significant in the men (0.66 g per kg BW, P = 0.013; 0.79 g per kg FFM, P = 0.02). The results show that in this group of healthy elderly adults protein requirements as assessed from leucine balance studies were either similar to or less than those of younger adults.

Adult↗
PubMed1997

Aging, protein requirements, and protein turnover.

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, indicates little reason for any revision. Furthermore, the 1985 recommendation is generally consistent with reports that the rate of whole-body protein turnover, a commonly assumed determinant of the protein requirement, exhibits minimal change with age per unit fat-free mass. Recent novel tracer studies aimed at evaluating protein requirements and turnover in a systematic way also support the 1985 recommendations. [1-13C]leucine balance studies have allowed measurement of metabolic demand from postabsorptive leucine oxidation and the efficiency of protein utilization from changes in leucine balance with feeding. The apparent protein requirement is metabolic demand divided by efficiency, an indication of protein needs and utilization during a standardized protocol at intakes similar to habitual ones. In healthy, mobile, elderly persons, metabolic demands are reduced by about one-third, with no significant impairment in efficiency of protein utilization. Thus, apparent protein requirements appear to fall with age from 0.98 +/- 0.17 to 0.69 +/- 0.22 g/kg. These changes with age reflect an improved restraint of proteolysis in the postabsorptive state, with little change with age in whole-body protein synthesis. The requirements of frail and immobile elderly and the efficiency of protein utilization of meals as eaten by elderly people remain to be evaluated.

Adult↗
PubMed1996

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.

Amino Acids↗
PubMed1996

Influences of dietary energy and protein on leucine kinetics during feeding in healthy adults.

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) were determined from plasma alpha-[1-13C]ketoisocaproate enrichment and expired 13CO2 excretion measured during the third hour of each 3-h period. Plasma insulin increased markedly with feeding to a level that was maintained with both diets. The negative postabsorptive leucine balance became less negative during the LP meals (P < 0.01) and was positive with the HP meals (P < 0.01). The significant responses to feeding (all P < 0.01) were for oxidation -13% (PA-LP), +50% (LP-HP), and +29% (PA-HP); for degradation -24% (PA-LP), -30% (LP-HP), and -47% (PA-HP); and for synthesis -14% (PA-LP), +29% (LP-HP), and +11% (PA-HP). These data support a feeding mechanism involving both an insulin-mediated, protein-conserving influence of dietary energy that inhibits degradation, lowers amino acid levels, and reduces oxidation, and amino acid-mediated augmentation of the inhibition of degradation, a stimulation of synthesis, and an increase in oxidation when leucine dietary supply exceeds the capacity for its net deposition.

Adult↗
PubMed1994

Nitrogen homeostasis in man: influence of protein intake on the amplitude of diurnal cycling of body nitrogen.

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 losses were determined from measured urinary N excretion corrected for changes in the body urea pool, and estimated faecal and miscellaneous losses. [13C]Leucine and [2H5]phenylalanine balances were measured during a primed, continuous infusion of the two amino acids during the fasting and feeding phase on the second day. 2. Increasing fasting N losses were observed (47 +/- 7, 60 +/- 6, 95 +/- 15 and 140 +/- 36 mg day-1 kg-1) on the four intakes, with corresponding increasing fed gains of 8.2 +/- 3.9, 40.2 +/- 7.1, 112 +/- 24 and 180 +/- 56 mg day-1 kg-1. 3. Increasing fed-state amino acid gains with increasing protein intake were observed with both [13C]leucine and [2H5]phenylalanine, whereas increasing fasting amino acid losses were confirmed with [13C]leucine. 4. The N equivalent of the leucine oxidation rate was mostly in the range of 10-50% lower than expected from the N excretion rates. This may reflect the timing of the amino acid balance measurements and non-uniform rates of gain and loss throughout the diurnal cycle. 5. We conclude on the basis of both N and amino acid balances that the amplitude of the diurnal cycling of body protein N in human adults increases with increasing dietary protein intake. Thus one component of the protein requirement for N balance reflects a demand for repletion of fasting losses which increases with increasing habitual protein intake.

Adult↗
PubMed1994

Nitrogen homeostasis in man: the diurnal responses of protein synthesis and degradation and amino acid oxidation to diets with increasing protein intakes.

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 8 h primed, continuous infusion during the fasting and feeding phase together with fed-state N turnover assessed with [15N]glycine after 12 days of adaptation to diets containing 0.36 (LP), 0.77 (MP), 1.59 (GP) and 2.07 (HP) g of protein day-1 kg-1. Measurements were also made of fasting and fed resting metabolic rate and plasma hormone levels. 2. Resting metabolic rate in the fasted and fed state was not influenced by dietary protein intake, but was increased by feeding (11-13%, P < 0.01) with no influence of dietary protein concentration. Fasting plasma insulin levels were not influenced by protein intake and were increased by feeding independent of protein intake. Fasted but not fed values of insulin-like growth factor-1 increased with protein intake, although no feeding response was observed. Thyroid hormones (free and total tri-iodothyronine) did not change in any state. 3. For leucine with increasing protein intake the increasing fasting losses reflected increasing rates of protein degradation, although the changes were small and only significant between GP and MP intakes. The increasing leucine gain on feeding was associated with increasing rates of protein synthesis and falling rates of protein degradation, reflecting a progressive inhibition of degradation with feeding, and a change from inhibition of synthesis (LP diet) to stimulation (GP and HP diets). Mean daily rates of synthesis and degradation did not change with protein intake. 4. Phenylalanine and tyrosine kinetics were calculated from adjusted values based on leucine kinetics and published data of the hepatic/plasma enrichment ratio. With the increased protein intake, the increasing fasting losses of phenylalanine (GP > MP) were mediated by increasing rates of degradation (paired t-tests). The increasing phenylalanine gain (GP > MP > LP) was due to increasing fed-state rates of synthesis and falling rates of degradation, reflecting a progressive inhibition of degradation, a stimulation of hydroxylation and a variable response of synthesis ranging from inhibition at the lowest intake to stimulation at higher intakes. For tyrosine a similar progressive inhibition of degradation with intake was shown. Mean daily rates of synthesis and degradation (phenylalanine) and degradation (tyrosine) did not change with protein intake.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Nitrogen homoeostasis in man: diurnal changes in nitrogen excretion, leucine oxidation and whole body leucine kinetics during a reduction from a high to a moderate protein intake.

1. The adaptation of the diurnal cycle of nitrogen (N) homeostasis 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 protein day-1 kg-1, N excretion fell slowly at a similar rate in fed and fasted states so that the lowered intake was unable to replete any of the postabsorptive losses for 3 days. There was a marked negative N balance, which persisted throughout the study, although with a significant reduction in N losses in both fed and fasted states on day 4, balances during days 4-9 (-32.8 +/- 28.3 mg of N day-1 kg-1) were less negative than during days 1-3 (-79.1 +/- 60.4 mg of N day-1 kg-1). 3. In experiment 2, during a 14 day period after a reduction from 1.89 to 0.77 g of protein day-1 kg-1, [1-13C]leucine oxidation and turnover were measured by primed intravenous infusion, during fasting and feeding in subjects before and on days 3, 7 and 14 after the dietary change. Leucine oxidation fell by 32% (P < 0.05) on day 3 in the fed state and by 12% (P < 0.05) during fasting, falling further in each case by day 7 with improved balance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1994

Dietary protein and the regulation of long-bone and muscle growth in the rat.

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 were made at 1, 3 and 7 days. In experiment 2, complete growth inhibition was induced by ad libitum feeding of a 0.5% protein diet with measurements at 7, 14 and 21 days followed by refeeding diets of 3%, 6%, 9%, 12% and 20% protein, with measurements after 3, 7, 10 and 14 days of refeeding (experimental days 24, 28, 31 and 35). Controls fed a 20% protein diet were studied at 0, 14, 21, 24, 28, 31 and 35 days. 2. Body weight growth stopped immediately in all reduced protein groups, with subsequent weight maintenance on the 7% protein diet, slight loss on the 3.5% protein diet or marked weight loss on the 0.5% protein diet, although food intake was maintained for 3 days, falling in all groups after this time. Inhibition of muscle growth was delayed in the 7% and 3.5% protein fed groups, with 12-15% increases in muscle weight after 7 days, but prompt growth inhibition occurred with the 0.5% protein diet with subsequent weight loss. In animals fed the control 20% protein diet, muscle weight (W) reflected tibial length (L) as W = L3.85/10(2.93) (r = 0.98, n = 98). Calculation of the muscle weight/bone length ratio (micrograms/mm3.85) indicated that a significant muscle deficit was apparent on day 3 and subsequently in the 0.5% protein fed rats, but not until day 7 in the 3.5% and 7% protein fed animals. 3. Total tibial length, epiphysis length and epiphyseal cartilage width were measured radiographically. In all groups there was no significant reduction in bone length growth during the first 3 days. After 3 days there were graded reductions on reduced protein intakes with complete inhibition on the 0.5% protein diet. Epiphyseal cartilage width responded sensitively, with a reduction within 24h of the 0.5% and the 3.5% protein diets, and within 3 days of the 7% protein diet. The epiphysis length was only minimally affected. 4. In experiment 2, food intake increased immediately on refeeding in all except the 3% protein fed group.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Dietary energy, glucocorticoids and the regulation of long bone and muscle growth in the rat.

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 radiographically. 2. In experiment 1, tibial length and gastrocnemius muscle growth were examined in ad libitum fed rats and during 4 days of severe energy restriction (25% ad libitum intake), starvation and ad libitum feeding with corticosterone treatment (10 mg/100 g), a mediator of the response to energy restriction. Weight loss occurred in all groups. Tibial growth continued in the 25% and starvation groups albeit at reduced rates with the inhibition of starvation > 25% group (P < 0.05), but was arrested after 2 days of corticosterone treatment. 3. Muscle growth inhibition was proportional to tibial growth inhibition of the 25% group, insofar as the muscle/bone ratio (W/L), was maintained. This inter-relationship between muscle and bone growth previously reported for ad libitum high-protein-fed rats, is likely to reflect the anabolic influence of bone on muscle via passive muscle stretching induced by length growth. For both starvation and corticosterone groups the muscle/bone ratio fell (P < 0.05 compared with the ad libitum group), suggesting that muscle growth inhibition included an additional direct catabolic influence of starvation and corticosterone treatment. 4. In experiment 2, measurements of bone, muscle and liver growth were made in rats fed 75%, or 50% and 25% ad libitum intakes with corticosterone treatment for 8 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Influence of dietary protein, energy and corticosteroids on protein turnover, proteoglycan sulphation and growth of long bone and skeletal muscle in the rat.

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 proteoglycan synthesis in bone and muscle to be established. 2. Protein deficiency was examined by ad libitum feeding of 20%, 7%, 3.5% and 0.5% protein diets with measurements at 1, 3 and 7 days (all diets), and 14 and 21 days (0.5% protein). In bone this induced delayed inhibition of tibial growth with parallel inhibition of protein synthesis, as measured by the phenylalanine flooding dose method. This was mediated by reductions in both ribosomal capacity (RNA/protein ratio) and activity (protein synthesis/RNA) in the 0.5% protein group. The pattern of inhibition of proteoglycan sulphation, measured as 35S uptake 60 min after injection of a tracer dose of labelled sulphate, was similar to that of protein synthesis. 3. In muscle there was an intermediate graded inhibition of protein synthesis by protein deficiency, mediated by reductions in both ribosomal capacity and activity in the 0.5% protein group, which preceded growth inhibition in the 7% and 3.5% groups, and which was progressive with time. Transient increases in proteolysis contributed to the growth inhibition is some groups, but the rate fell eventually in the 0.5% group. The pattern of response of proteoglycan sulphation differed from protein synthesis with a delayed inhibition, but with subsequent marked reduction. 4. Energy restriction was induced by diets fed for 4 or 8 days at 75%, 50% and 25% ad libitum intakes with protein intakes held constant, and corticosterone treatment involved a dose of 10 mg day-1 100-1 g (subcutaneous) with ad libitum feeding. In bone this induced a pattern of length growth inhibition which was dissociated from inhibition of protein synthesis in the moderately restricted (75% and 50%) groups. Only in the 25% group and in the 8 day corticosterone group was protein synthesis inhibited, through reductions in ribosomal capacity and activity. 35S uptake was also dissociated from growth inhibition, with reduced 35S uptake observed only after corticosterone treatment or 8 days of the 50% or 25% diets. 5. In muscle the energy restriction and corticosterone treatment induced parallel inhibitions of growth and protein synthesis, mediated by similar graded reductions in the RNA/protein ratios and in the 25% group in the KRNA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

The effects of two different periods of weight-reduction on selected performance parameters in elite lightweight oarswomen.

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 measurements. Maximal oxygen intake (VO2max), respiratory anaerobic threshold (Tvent), upper body anaerobic peak power (PP) and mean power (MP) outputs, and knee flexor (KF) and extensor (KE) isokinetic peak torques were among the physiological parameters assessed. No statistical differences were noted between the data obtained prior to the two weight-reduction periods, and both periods resulted in lower BW (p < 0.001) and FFM (p < 0.05); approximately 50% of the lost BW was FFM. At the end of the two-month weight-reduction period Tvent (p < 0.02) and KF (p < 0.02) decreased. In contrast, a similar BW loss during the four-month period was associated with higher VO2max (p < 0.01) and PP (p < 0.05) compared with values prior to weight reduction. Comparisons between the percentage changes pre to post BW loss showed that the longer weight-reduction period was associated with significantly improved VO2max (p < 0.01), Tvent (p < 0.005), PP (p < 0.05) and KF (p < 0.05). We conclude: a) the proportion (50%) of weight lost as FFM in the present elite rowers is higher than the suggested optimal figure of 22%, and b) compared to four months, 6-7% of BW loss over two months may adversely influence fitness-related parameters in international lightweight oarswomen.

Adipose Tissue↗
PubMed1993

Interactions between growth hormone and nutrition in hypophysectomized rats: body composition and production of insulin-like growth factor-I.

Hypophysectomy of adult rats results in a loss of body growth which can be reversed by treatment with GH. The increased growth caused by administration of GH is accompanied by an increase in food consumption. The effects of GH and interactions with nutrition were investigated by treating hypophysectomized rats with GH and either providing unrestricted food or preventing the increased food consumption by pair-feeding with the same intake as that of the hypophysectomized animals. Over the 7-day experimental period, the GH-treated animals grew significantly when food was available ad libitum but did not gain body weight when an increase in food intake was prevented. However, there was a significant interaction between GH and nutrition on body composition; GH significantly decreased body fat and increased the protein: fat ratio only in the animals with the restricted intake. Gastrocnemius muscle weight was increased by GH regardless of food intake, but heart weight did not increase and liver weight was actually decreased by GH treatment when food intake was restricted. Serum concentrations of insulin and insulin-like growth factor-I (IGF-I) were increased by GH in the rats with food available ad libitum but not in the pair-fed rats. However, the liver concentration of IGF-I and its mRNA were increased by GH although the increase in IGF-I mRNA was modulated by the restricted food intake. The decreased weight of the liver in the pair-fed GH-treated rats, despite the increase in IGF-I mRNA, suggests that IGF-I does not influence liver growth. In the gastrocnemius muscle, however, GH increased IGF-I mRNA concentration similarly in both rats with food available ad libitum and in pair-fed rats. Decreased nutrition therefore modulated the action of GH but emphasized its nutrient partitioning effect, thus increasing the anabolic drive towards skeletal muscle growth; this appeared to be mediated by the local production of IGF-I within the muscle.

Animal Nutritional Physiological Phenomena↗