Leonard Hoffer - Academia.edu (original) (raw)
Papers by Leonard Hoffer
Plasma concentrations of the branchedchain amino acids leucine, isoleucine and valine, and those ... more Plasma concentrations of the branchedchain amino acids leucine, isoleucine and valine, and those of leucine's and isoleucine's transamination products «-ketoisocaproic acid (KICA) and a-keto-0methylvaleric acid (KMVA), respectively, are known to increase after a protein meal or during extended fasting, but little or no increase in the concentration of valine's transamination product, a-ketoisovaleric acid (KIVA), has been observed under these conditions. To determine whether this could be explained by the conversion of KIVA to its a-hydroxy analogue, we measured the plasma concentrations of KICA, KMVA and KIVA, as well as their a-hydroxy analogues [a-hydroxyisocaproic acid (HICA), a-hydroxy-/S-methylvaleric acid (HMVA) and a-hydroxyisovaleric acid (HIVA)], in normal volun teers immediately after a protein meal or during a 60-h fast. We also determined the oxidoreduction equilibrium constants for HIVA/KIVA and HICA/KICA and their extent of plasma protein binding. In subjects in the postabsorptive state, the plasma concentrations of KICA and KMVA were 100 times those of HICA and HMVA, whereas that of KIVA was only twice that of HIVA. Shortly after a protein meal, KICA and KMVA concentrations increased significantly by 30 and 60%, respectively, whereas that of KIVA decreased by 25% (P < 0.05). HICA, HMVA and HIVA concentrations did not change. During prolonged fasting the plasma concentra tions of all six metabolites increased gradually. The high plasma keto/hydroxy acid ratios were not related to their Keq, which favored a-hydroxy analogue formation. The reduction of the branched-chain a-keto acids to their ahydroxy analogues seems to take place too slowly to attain thermodynamic equilibrium. The acute decrease in plasma KIVA after a protein meal may be due to a lower rate of valine intracellular transport or transamination in the presence of increased plasma leucine and isoleucine concentrations.
American Journal of Clinical Nutrition
Estimates of plasma alanine flux as measured in humans using L-['5N]alanine or L-[3,3,3-2H3]alani... more Estimates of plasma alanine flux as measured in humans using L-['5N]alanine or L-[3,3,3-2H3]alanine were compared by simultaneous intravenous infusion of both tracers. Plasma isotope enrichments were measured by chemical ionization gas chromatography-mass spectrometry. In 16 obese women before and during a hypocalonc diet and in 4 normal men in the postabsorptive and fed states, the fluxes were highly correlated (r2 = 0.93) although plasma alanine flux with the 2H tracer was two to three times greater than that obtamed with [15Njalanine. The fluxes decreased with the hypocaloric diet in obese subjects and increased during the fed state in healthy adults. Thus, although the estimates of alanine flux differed according to the tracer used, both appear to give equivalent information about changes in alanine kinetics induced by the nutritional conditions examined. Am J Clin Nutr 1988:48: 10 10-4.
The American journal of physiology
In a study of the mechanism of adaptation to protein deficiency, 10 moderately obese women underw... more In a study of the mechanism of adaptation to protein deficiency, 10 moderately obese women underwent a 3-wk fast followed by random allocation to a 1-wk refeeding regimen providing 80 g carbohydrate or protein. Protein metabolism was studied by means of nitrogen (N) balance, urinary 3-methylhistidine excretion, and postabsorptive plasma leucine flux using L-[1-13C]leucine infusions. After the 3-wk fast, plasma leucine flux and 3-methylhistidine excretion both decreased by 31% from control diet values (P less than 0.01), and N balance was -5.9 g/day. After protein refeeding, N balance was positive (+1.7 g/day, P less than 0.05) whereas leucine flux was unchanged from prolonged fasting values. After carbohydrate refeeding, N balance improved to -3.1 g N/day, whereas leucine flux decreased by a further 18% (P less than 0.05). Protein and carbohydrate refeeding were associated with further 23 and 31% reductions of 3-methylhistidine excretion compared with prolonged fasting (P less than 0.05). The results support the hypothesis that improved efficiency of protein retention in starvation is intimately associated with a decreased rate of protein turnover.
The American journal of physiology
Eight normal subjects, four subjects with intensively treated insulin-dependent diabetes mellitus... more Eight normal subjects, four subjects with intensively treated insulin-dependent diabetes mellitus (IDDM), and six subjects with conventionally treated IDDM consumed a test meal of 0.5 g protein and 10 kcal per kg body weight, first while adapted to a conventional diet high in protein, and then again after 5 days of dietary protein restriction. Metabolic N balance (N consumed minus urea production) and net protein utilization were measured over the 9 h after consumption of the test meal, as was recovery in urea of 15N from a tracer dose of [15N]alanine included in each test meal. After the first test meal, N balance and net protein utilization were similar and close to zero for all groups. After the second test meal, N balance and net protein utilization became positive for all groups (P < 0.05) but significantly less so (P < 0.05) for the conventionally treated than for the normal and intensively treated diabetic subjects. 15N recovery in urea was reduced for all groups after the second test meal (P < 0.05) but probably less effectively (P < 0.09) for the conventionally treated diabetic subjects. Metabolic adaptation to protein restriction may be less effective than normal in conventionally treated IDDM.
American Journal of Clinical Nutrition
We postulated that the return to nitrogen
The American journal of physiology
It is well known that inadequate insulin therapy stimulates body protein loss in insulin-dependen... more It is well known that inadequate insulin therapy stimulates body protein loss in insulin-dependent diabetes mellitus (IDDM). It is less well known, however, that accelerated body protein loss (as indicated by increased leucine oxidation) occurs in IDDM even during conventional glycemic control. It is not known whether intensified insulin therapy fully normalizes protein oxidation or, more importantly, whether such therapy is sufficient to allow the adaptive decrease of protein oxidation that normally occurs when protein intake is restricted below the customary surfeit level. We used two measures of protein oxidation [daily urinary nitrogen (N) excretion over several days of intensive insulin therapy and plasma [1-13C]leucine oxidation during short-term strict euglycemia] to assess the response of 7 men with IDDM and 12 normal men after adaptation first to a control diet providing maintenance energy and conventional (surfeit) protein then to an isoenergetic protein-free diet. After adaptation to the protein-free diet and during short-term strict euglycemia achieved using intravenous insulin, leucine turnover and oxidation decreased equivalently in normal and diabetic subjects. However, daily urinary obligatory N excretion, which indicated the effect of the low-protein diet and intensive subcutaneous insulin therapy over several days, was increased by 18% in the diabetic group (P less than 0.05). Even mildly elevated average blood glucose values well within the guidelines for intensive therapy were strongly correlated with high rates of urinary N excretion (r = 0.97, P = 0.0002). Thus insulin therapy of IDDM that imposes strict euglycemia is compatible with a normal ability to diminish body protein oxidation in response to protein restriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Orthomolecular Medicine
The American journal of physiology
Journal of Nutrition
The volume of human extracellular water (ECW) may be estimated from the sulfate space (SS). Altho... more The volume of human extracellular water (ECW) may be estimated from the sulfate space (SS). Although it may better approximate ECW volume than the bromide space, a common alternative, SS measurement is limited by the need to administer a radioactive substance, sodium [ 35 S]sulfate. In this paper, we demonstrate the measurement of the SS using the stable isotope, sodium [ 34 S]sulfate. Eight healthy nonobese men ingested 0.50 -0.78 mg (3.47-5.42 mol) Na 2 34 SO 4 /kg body weight and 30 mg NaBr/kg body weight. Sulfate concentrations and 34 SO 4 enrichments were measured by electrospray tandem mass spectrometry before and during the 5 h after tracer administration. SS was calculated by linear extrapolation of the natural logarithm of serum 34 SO 4 concentrations obtained at h 2, 3 and 4 compared with h 3, 4 and 5. The SS obtained using values between h 3 and 5 (187 Ϯ 17 mL/kg) was similar to published determinations using intravenous or oral radiosulfate, and was 80% of the simultaneously measured corrected bromide space (234 Ϯ 10 mL/kg, P ϭ 0.01). Oral sodium [ 34 S]sulfate administration is a suitable technique for measuring ECW and avoids radiation exposure. J. Nutr. 129: 722-727, 1999.
American journal of physiology. Endocrinology and metabolism, 2003
Persons with conventionally treated insulin-dependent diabetes mellitus (IDDM) appear to be impai... more Persons with conventionally treated insulin-dependent diabetes mellitus (IDDM) appear to be impaired in their ability to reduce fed-state urea production appropriately in response to dietary protein restriction (Hoffer LJ, Taveroff A, and Schiffrin A. Am J Physiol 272: E59-E67, 1997). To determine whether these conclusions apply to whole body sulfur amino acid (SAA) catabolism, we used samples from this protocol to measure daily urinary sulfate excretion and fed-state sulfate production after a high-protein test meal before and after dietary protein restriction. Eight normal subjects and six IDDM subjects treated with twice-daily intermediate- and short-acting insulin consumed a mixed test meal containing 0.50 g protein/kg after adaptation to 4 days of high protein intake (1.28 g protein/kg body wt) and again after 5 days of dietary protein restriction (0.044 g/kg). Adaptation to protein restriction decreased daily urinary sulfate and urea-N excretion by approximately 80%. Over the ...
The American journal of physiology, 1989
In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone b... more In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylation fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen...
British Journal of Nutrition, 1985
1. The effects of meal consumption on plasma leucine and alanine kinetics were studied using a si... more 1. The effects of meal consumption on plasma leucine and alanine kinetics were studied using a simultaneous, primed, continuous infusion of L-[ I-13C]leucine and ~-[3,3,3-~H,]alanine in four healthy, young, adult male subjects. The study included an evaluation of the effect of sampling site on plasma amino acid kinetics, with blood being drawn simultaneously from an antecubital and dorsal heated hand vein.
Nutrition, 2011
Objective: Hypovitaminosis C and D are highly prevalent in acutely hospitalized patients, but the... more Objective: Hypovitaminosis C and D are highly prevalent in acutely hospitalized patients, but the clinical significance of these biochemical abnormalities is not known. Because deficiencies of vitamin C and D have been linked to psychologic abnormalities, vitamin C or D provision could improve the mood state of acutely hospitalized patients. Methods: Double-blind clinical trial of the effect of vitamin C (500 mg twice daily) or vitamin D (1000 IU twice daily) on mood, as assessed with a validated instrument, the Profile of Mood States. Results: Vitamin C therapy increased plasma (P < 0.0001) and mononuclear leukocyte (P ¼ 0.014) vitamin C concentrations and was associated with a 34% reduction in mood disturbance (P ¼ 0.013). Vitamin D therapy increased plasma 25-hydroxyvitamin D concentrations (P ¼ 0.0004), but had no significant effect on mood. Conclusions: Treatment of hypovitaminosis C improves the mood state of acutely hospitalized patients.
Nutrition, 2010
Objective: Recent studies have indicated a high prevalence of hypovitaminosis C in acutely hospit... more Objective: Recent studies have indicated a high prevalence of hypovitaminosis C in acutely hospitalized patients. It is unclear whether hypovitaminosis C in this setting represents deficiency or tissue redistribution of the vitamin as part of the acute-phase response. Methods: We administered vitamin C for 1 wk to acutely hospitalized, but not critically ill patients with hypovitaminosis C, on the assumption that a large increase in plasma and mononuclear leukocyte vitamin C concentrations, a decrease in metabolic markers of oxidative stress, or an improvement in psychologic mood state would implicate the initial condition as nutritional deficiency rather than tissue redistribution. Results: Vitamin C administration increased plasma and mononuclear leukocyte vitamin C concentrations from subnormal (16.3 AE 12.4 mmol/L and 6.5 AE 5.5 mmol/L, respectively) to normal (71.0 AE 30.9 mmol/L, P < 0.0001, and 8.2 AE 6.8 mmol/L, P < 0.015); the mood disturbance score improved by 33% (P < 0.008). There was no increase in plasma glutathione concentrations or a reduction in plasma or mononuclear leukocyte malondialdehyde concentrations. An inverse relation was observed between plasma C-reactive protein and plasma vitamin C concentrations (P ¼ 0.006). Conclusion: Although associated with systemic inflammation, the metabolic features of hypovitaminosis C in acutely hospitalized, non-critically ill patients are more consistent with deficiency than with tissue redistribution.
Metabolism, 1994
The mechanism governing short-term adaptation to dietary protein restriction was investigated in ... more The mechanism governing short-term adaptation to dietary protein restriction was investigated in nine normal adults by measuring their metabolic response to a standard mixed meal, first while they were adapted to a conventional, high-protein diet (day 1) and then again after they had eaten two low-protein meals (day 2). Urea appearance (measured as the sum of its urinary excretion and the change in body urea pool size), body retention of 15N-alanine included in each test meal, and whole-body protein turnover were calculated over the 9 hours following meal consumption on each day. Postprandial urea nitrogen appearance was 5.05 +/- 0.26 g/9 h on day 1 and decreased to 4.16 +/- 0.31 on day 2 (P < .05). Whole-body N flux (Q), protein synthesis (S), and protein breakdown (B) all decreased significantly on day 2 as assessed using either urea or ammonium end-product enrichments; however, recovery of 15N in the test meal as 15N-urea was similar on both days, approximately 22%. It is concluded that short-term metabolic adaptation occurs within two meals of reduced protein intake. The mechanism appears not to involve selectively an increased "first-pass" retention of dietary amino acids, but rather a general reduction in fed-state whole-body protein breakdown.
Metabolism, 1994
We tested whether the primary or reciprocal pool models for whole-body leucine kinetics accuratel... more We tested whether the primary or reciprocal pool models for whole-body leucine kinetics accurately depict human adaptation to protein deficiency and repletion in the fed state by comparing model-derived leucine oxidation with urea appearance calculated from urinary urea excretion and changes in the body urea pool. Five normal men consumed a control diet providing maintenance energy and 80 g protein/d for 5 days; this was followed by 7 days of an isoenergetic protein-free diet, and finally by a return to the original control diet for 5 days. At the end of each dietary period, urea appearance and leucine oxidation were measured during a 4-hour intravenous infusion of crystalline amino acids providing a total N to leucine N ratio similar to that in mixed body proteins. Primary pool-derived fed-state leucine oxidation decreased after adaptation to protein deficiency and remained low during refeeding (18.6 +/- 1.2, 13.2 +/- 1.1, and 15.0 +/- 1.8 mumol.kg-1.h-1, respectively, P < .01), in agreement with the physiologic prediction. A similar pattern occurred with the reciprocal pool model (24.4 +/- 2.7, 17.3 +/- 2.0, and 20.3 +/- 2.7 mumol.kg-1.h-1, P < .01) as well as with urea N appearance (3.06 +/- 0.32, 2.34 +/- 0.24, and 2.38 +/- 0.26 mmol N.kg-1.4 h-1, P < .05). Despite these relative agreements, absolute rates of whole-body amino acid oxidation were 25% (reciprocal pool model) to 43% (primary pool model) lower than when estimated from urea N appearance.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolism, 1984
Fasting plasma glucose turnover, urinary 3-methylhistidine excretion, and fasting plasma protein ... more Fasting plasma glucose turnover, urinary 3-methylhistidine excretion, and fasting plasma protein profiles were compared in a 4-week randomized clinical trial of two very low-calorie weight-reduction diets. Diet A (360 kcal) provided 1.5 g egg protein per kg ideal body weight (IBW) but no carbohydrate. Diet B (340 kcal) provided 0.8 g egg protein per kg IBW plus 0.7 g carbohydrate per kg IBW. Eleven moderately obese healthy young women were studied. After 3 weeks of dieting, fasting plasma glucose appearance and oxidation decreased by equal amounts (20% and 30%, respectively) for both diets. 3-methylhistidine excretion remained at control rates for the first week on the diets, then fell by equal amounts (25% to 30%) with both diets. Similar declines were observed for both diets in serum prealbumin and retinol-binding protein concentrations. Mean serum transferrin declined with both diets, but the changes were not statistically significant. Serum albumin was unchanged by either diet. Thus, there were no significant differences between the two diets with regard to any of the measured parameters.
Metabolism, 1990
To study the influence of previous dietary protein depletion on nitrogen (N) loss and protein tur... more To study the influence of previous dietary protein depletion on nitrogen (N) loss and protein turnover during a total fast, we measured plasma leucine kinetics and urinary N and 3-methylhistidine (3MH) excretion in obese and normal subjects. In one study, 10 moderately obese women fasted for 2 weeks after adaptation either to a normal maintenance intake of 80 g protein and 150% of estimated resting energy expenditure (control group), or to 10 days of a 950-kcal, 200-g carbohydrate, 4-g protein diet (depletion group), with measurement of postabsorptive (or fasting) plasma leucine turnover on the maintenance diet and after 3 and 10 days of fasting. As measured after 10 days of fasting, body N loss was blunted by 17% when preceded by the protein-deficient diet. Plasma leucine flux and oxidation of the control group increased in early fasting and decreased by 10 days, in accordance with previous reports. Results for the depletion group were similar in absolute magnitude, despite the preceding protein-deficient diet. In a second study of five normal men, leucine kinetics were measured on a maintenance diet, after 10 days of a protein-free diet, and after 3 days of fasting. After protein depletion, leucine flux decreased by 19% (P less than .05). After 3 days fasting, leucine flux was 16% higher than on the maintenance diet (P less than .05), but 44% higher than the value on the protein-free diet 3 days earlier (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma concentrations of the branchedchain amino acids leucine, isoleucine and valine, and those ... more Plasma concentrations of the branchedchain amino acids leucine, isoleucine and valine, and those of leucine's and isoleucine's transamination products «-ketoisocaproic acid (KICA) and a-keto-0methylvaleric acid (KMVA), respectively, are known to increase after a protein meal or during extended fasting, but little or no increase in the concentration of valine's transamination product, a-ketoisovaleric acid (KIVA), has been observed under these conditions. To determine whether this could be explained by the conversion of KIVA to its a-hydroxy analogue, we measured the plasma concentrations of KICA, KMVA and KIVA, as well as their a-hydroxy analogues [a-hydroxyisocaproic acid (HICA), a-hydroxy-/S-methylvaleric acid (HMVA) and a-hydroxyisovaleric acid (HIVA)], in normal volun teers immediately after a protein meal or during a 60-h fast. We also determined the oxidoreduction equilibrium constants for HIVA/KIVA and HICA/KICA and their extent of plasma protein binding. In subjects in the postabsorptive state, the plasma concentrations of KICA and KMVA were 100 times those of HICA and HMVA, whereas that of KIVA was only twice that of HIVA. Shortly after a protein meal, KICA and KMVA concentrations increased significantly by 30 and 60%, respectively, whereas that of KIVA decreased by 25% (P < 0.05). HICA, HMVA and HIVA concentrations did not change. During prolonged fasting the plasma concentra tions of all six metabolites increased gradually. The high plasma keto/hydroxy acid ratios were not related to their Keq, which favored a-hydroxy analogue formation. The reduction of the branched-chain a-keto acids to their ahydroxy analogues seems to take place too slowly to attain thermodynamic equilibrium. The acute decrease in plasma KIVA after a protein meal may be due to a lower rate of valine intracellular transport or transamination in the presence of increased plasma leucine and isoleucine concentrations.
American Journal of Clinical Nutrition
Estimates of plasma alanine flux as measured in humans using L-['5N]alanine or L-[3,3,3-2H3]alani... more Estimates of plasma alanine flux as measured in humans using L-['5N]alanine or L-[3,3,3-2H3]alanine were compared by simultaneous intravenous infusion of both tracers. Plasma isotope enrichments were measured by chemical ionization gas chromatography-mass spectrometry. In 16 obese women before and during a hypocalonc diet and in 4 normal men in the postabsorptive and fed states, the fluxes were highly correlated (r2 = 0.93) although plasma alanine flux with the 2H tracer was two to three times greater than that obtamed with [15Njalanine. The fluxes decreased with the hypocaloric diet in obese subjects and increased during the fed state in healthy adults. Thus, although the estimates of alanine flux differed according to the tracer used, both appear to give equivalent information about changes in alanine kinetics induced by the nutritional conditions examined. Am J Clin Nutr 1988:48: 10 10-4.
The American journal of physiology
In a study of the mechanism of adaptation to protein deficiency, 10 moderately obese women underw... more In a study of the mechanism of adaptation to protein deficiency, 10 moderately obese women underwent a 3-wk fast followed by random allocation to a 1-wk refeeding regimen providing 80 g carbohydrate or protein. Protein metabolism was studied by means of nitrogen (N) balance, urinary 3-methylhistidine excretion, and postabsorptive plasma leucine flux using L-[1-13C]leucine infusions. After the 3-wk fast, plasma leucine flux and 3-methylhistidine excretion both decreased by 31% from control diet values (P less than 0.01), and N balance was -5.9 g/day. After protein refeeding, N balance was positive (+1.7 g/day, P less than 0.05) whereas leucine flux was unchanged from prolonged fasting values. After carbohydrate refeeding, N balance improved to -3.1 g N/day, whereas leucine flux decreased by a further 18% (P less than 0.05). Protein and carbohydrate refeeding were associated with further 23 and 31% reductions of 3-methylhistidine excretion compared with prolonged fasting (P less than 0.05). The results support the hypothesis that improved efficiency of protein retention in starvation is intimately associated with a decreased rate of protein turnover.
The American journal of physiology
Eight normal subjects, four subjects with intensively treated insulin-dependent diabetes mellitus... more Eight normal subjects, four subjects with intensively treated insulin-dependent diabetes mellitus (IDDM), and six subjects with conventionally treated IDDM consumed a test meal of 0.5 g protein and 10 kcal per kg body weight, first while adapted to a conventional diet high in protein, and then again after 5 days of dietary protein restriction. Metabolic N balance (N consumed minus urea production) and net protein utilization were measured over the 9 h after consumption of the test meal, as was recovery in urea of 15N from a tracer dose of [15N]alanine included in each test meal. After the first test meal, N balance and net protein utilization were similar and close to zero for all groups. After the second test meal, N balance and net protein utilization became positive for all groups (P < 0.05) but significantly less so (P < 0.05) for the conventionally treated than for the normal and intensively treated diabetic subjects. 15N recovery in urea was reduced for all groups after the second test meal (P < 0.05) but probably less effectively (P < 0.09) for the conventionally treated diabetic subjects. Metabolic adaptation to protein restriction may be less effective than normal in conventionally treated IDDM.
American Journal of Clinical Nutrition
We postulated that the return to nitrogen
The American journal of physiology
It is well known that inadequate insulin therapy stimulates body protein loss in insulin-dependen... more It is well known that inadequate insulin therapy stimulates body protein loss in insulin-dependent diabetes mellitus (IDDM). It is less well known, however, that accelerated body protein loss (as indicated by increased leucine oxidation) occurs in IDDM even during conventional glycemic control. It is not known whether intensified insulin therapy fully normalizes protein oxidation or, more importantly, whether such therapy is sufficient to allow the adaptive decrease of protein oxidation that normally occurs when protein intake is restricted below the customary surfeit level. We used two measures of protein oxidation [daily urinary nitrogen (N) excretion over several days of intensive insulin therapy and plasma [1-13C]leucine oxidation during short-term strict euglycemia] to assess the response of 7 men with IDDM and 12 normal men after adaptation first to a control diet providing maintenance energy and conventional (surfeit) protein then to an isoenergetic protein-free diet. After adaptation to the protein-free diet and during short-term strict euglycemia achieved using intravenous insulin, leucine turnover and oxidation decreased equivalently in normal and diabetic subjects. However, daily urinary obligatory N excretion, which indicated the effect of the low-protein diet and intensive subcutaneous insulin therapy over several days, was increased by 18% in the diabetic group (P less than 0.05). Even mildly elevated average blood glucose values well within the guidelines for intensive therapy were strongly correlated with high rates of urinary N excretion (r = 0.97, P = 0.0002). Thus insulin therapy of IDDM that imposes strict euglycemia is compatible with a normal ability to diminish body protein oxidation in response to protein restriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Orthomolecular Medicine
The American journal of physiology
Journal of Nutrition
The volume of human extracellular water (ECW) may be estimated from the sulfate space (SS). Altho... more The volume of human extracellular water (ECW) may be estimated from the sulfate space (SS). Although it may better approximate ECW volume than the bromide space, a common alternative, SS measurement is limited by the need to administer a radioactive substance, sodium [ 35 S]sulfate. In this paper, we demonstrate the measurement of the SS using the stable isotope, sodium [ 34 S]sulfate. Eight healthy nonobese men ingested 0.50 -0.78 mg (3.47-5.42 mol) Na 2 34 SO 4 /kg body weight and 30 mg NaBr/kg body weight. Sulfate concentrations and 34 SO 4 enrichments were measured by electrospray tandem mass spectrometry before and during the 5 h after tracer administration. SS was calculated by linear extrapolation of the natural logarithm of serum 34 SO 4 concentrations obtained at h 2, 3 and 4 compared with h 3, 4 and 5. The SS obtained using values between h 3 and 5 (187 Ϯ 17 mL/kg) was similar to published determinations using intravenous or oral radiosulfate, and was 80% of the simultaneously measured corrected bromide space (234 Ϯ 10 mL/kg, P ϭ 0.01). Oral sodium [ 34 S]sulfate administration is a suitable technique for measuring ECW and avoids radiation exposure. J. Nutr. 129: 722-727, 1999.
American journal of physiology. Endocrinology and metabolism, 2003
Persons with conventionally treated insulin-dependent diabetes mellitus (IDDM) appear to be impai... more Persons with conventionally treated insulin-dependent diabetes mellitus (IDDM) appear to be impaired in their ability to reduce fed-state urea production appropriately in response to dietary protein restriction (Hoffer LJ, Taveroff A, and Schiffrin A. Am J Physiol 272: E59-E67, 1997). To determine whether these conclusions apply to whole body sulfur amino acid (SAA) catabolism, we used samples from this protocol to measure daily urinary sulfate excretion and fed-state sulfate production after a high-protein test meal before and after dietary protein restriction. Eight normal subjects and six IDDM subjects treated with twice-daily intermediate- and short-acting insulin consumed a mixed test meal containing 0.50 g protein/kg after adaptation to 4 days of high protein intake (1.28 g protein/kg body wt) and again after 5 days of dietary protein restriction (0.044 g/kg). Adaptation to protein restriction decreased daily urinary sulfate and urea-N excretion by approximately 80%. Over the ...
The American journal of physiology, 1989
In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone b... more In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylation fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen...
British Journal of Nutrition, 1985
1. The effects of meal consumption on plasma leucine and alanine kinetics were studied using a si... more 1. The effects of meal consumption on plasma leucine and alanine kinetics were studied using a simultaneous, primed, continuous infusion of L-[ I-13C]leucine and ~-[3,3,3-~H,]alanine in four healthy, young, adult male subjects. The study included an evaluation of the effect of sampling site on plasma amino acid kinetics, with blood being drawn simultaneously from an antecubital and dorsal heated hand vein.
Nutrition, 2011
Objective: Hypovitaminosis C and D are highly prevalent in acutely hospitalized patients, but the... more Objective: Hypovitaminosis C and D are highly prevalent in acutely hospitalized patients, but the clinical significance of these biochemical abnormalities is not known. Because deficiencies of vitamin C and D have been linked to psychologic abnormalities, vitamin C or D provision could improve the mood state of acutely hospitalized patients. Methods: Double-blind clinical trial of the effect of vitamin C (500 mg twice daily) or vitamin D (1000 IU twice daily) on mood, as assessed with a validated instrument, the Profile of Mood States. Results: Vitamin C therapy increased plasma (P < 0.0001) and mononuclear leukocyte (P ¼ 0.014) vitamin C concentrations and was associated with a 34% reduction in mood disturbance (P ¼ 0.013). Vitamin D therapy increased plasma 25-hydroxyvitamin D concentrations (P ¼ 0.0004), but had no significant effect on mood. Conclusions: Treatment of hypovitaminosis C improves the mood state of acutely hospitalized patients.
Nutrition, 2010
Objective: Recent studies have indicated a high prevalence of hypovitaminosis C in acutely hospit... more Objective: Recent studies have indicated a high prevalence of hypovitaminosis C in acutely hospitalized patients. It is unclear whether hypovitaminosis C in this setting represents deficiency or tissue redistribution of the vitamin as part of the acute-phase response. Methods: We administered vitamin C for 1 wk to acutely hospitalized, but not critically ill patients with hypovitaminosis C, on the assumption that a large increase in plasma and mononuclear leukocyte vitamin C concentrations, a decrease in metabolic markers of oxidative stress, or an improvement in psychologic mood state would implicate the initial condition as nutritional deficiency rather than tissue redistribution. Results: Vitamin C administration increased plasma and mononuclear leukocyte vitamin C concentrations from subnormal (16.3 AE 12.4 mmol/L and 6.5 AE 5.5 mmol/L, respectively) to normal (71.0 AE 30.9 mmol/L, P < 0.0001, and 8.2 AE 6.8 mmol/L, P < 0.015); the mood disturbance score improved by 33% (P < 0.008). There was no increase in plasma glutathione concentrations or a reduction in plasma or mononuclear leukocyte malondialdehyde concentrations. An inverse relation was observed between plasma C-reactive protein and plasma vitamin C concentrations (P ¼ 0.006). Conclusion: Although associated with systemic inflammation, the metabolic features of hypovitaminosis C in acutely hospitalized, non-critically ill patients are more consistent with deficiency than with tissue redistribution.
Metabolism, 1994
The mechanism governing short-term adaptation to dietary protein restriction was investigated in ... more The mechanism governing short-term adaptation to dietary protein restriction was investigated in nine normal adults by measuring their metabolic response to a standard mixed meal, first while they were adapted to a conventional, high-protein diet (day 1) and then again after they had eaten two low-protein meals (day 2). Urea appearance (measured as the sum of its urinary excretion and the change in body urea pool size), body retention of 15N-alanine included in each test meal, and whole-body protein turnover were calculated over the 9 hours following meal consumption on each day. Postprandial urea nitrogen appearance was 5.05 +/- 0.26 g/9 h on day 1 and decreased to 4.16 +/- 0.31 on day 2 (P < .05). Whole-body N flux (Q), protein synthesis (S), and protein breakdown (B) all decreased significantly on day 2 as assessed using either urea or ammonium end-product enrichments; however, recovery of 15N in the test meal as 15N-urea was similar on both days, approximately 22%. It is concluded that short-term metabolic adaptation occurs within two meals of reduced protein intake. The mechanism appears not to involve selectively an increased "first-pass" retention of dietary amino acids, but rather a general reduction in fed-state whole-body protein breakdown.
Metabolism, 1994
We tested whether the primary or reciprocal pool models for whole-body leucine kinetics accuratel... more We tested whether the primary or reciprocal pool models for whole-body leucine kinetics accurately depict human adaptation to protein deficiency and repletion in the fed state by comparing model-derived leucine oxidation with urea appearance calculated from urinary urea excretion and changes in the body urea pool. Five normal men consumed a control diet providing maintenance energy and 80 g protein/d for 5 days; this was followed by 7 days of an isoenergetic protein-free diet, and finally by a return to the original control diet for 5 days. At the end of each dietary period, urea appearance and leucine oxidation were measured during a 4-hour intravenous infusion of crystalline amino acids providing a total N to leucine N ratio similar to that in mixed body proteins. Primary pool-derived fed-state leucine oxidation decreased after adaptation to protein deficiency and remained low during refeeding (18.6 +/- 1.2, 13.2 +/- 1.1, and 15.0 +/- 1.8 mumol.kg-1.h-1, respectively, P < .01), in agreement with the physiologic prediction. A similar pattern occurred with the reciprocal pool model (24.4 +/- 2.7, 17.3 +/- 2.0, and 20.3 +/- 2.7 mumol.kg-1.h-1, P < .01) as well as with urea N appearance (3.06 +/- 0.32, 2.34 +/- 0.24, and 2.38 +/- 0.26 mmol N.kg-1.4 h-1, P < .05). Despite these relative agreements, absolute rates of whole-body amino acid oxidation were 25% (reciprocal pool model) to 43% (primary pool model) lower than when estimated from urea N appearance.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolism, 1984
Fasting plasma glucose turnover, urinary 3-methylhistidine excretion, and fasting plasma protein ... more Fasting plasma glucose turnover, urinary 3-methylhistidine excretion, and fasting plasma protein profiles were compared in a 4-week randomized clinical trial of two very low-calorie weight-reduction diets. Diet A (360 kcal) provided 1.5 g egg protein per kg ideal body weight (IBW) but no carbohydrate. Diet B (340 kcal) provided 0.8 g egg protein per kg IBW plus 0.7 g carbohydrate per kg IBW. Eleven moderately obese healthy young women were studied. After 3 weeks of dieting, fasting plasma glucose appearance and oxidation decreased by equal amounts (20% and 30%, respectively) for both diets. 3-methylhistidine excretion remained at control rates for the first week on the diets, then fell by equal amounts (25% to 30%) with both diets. Similar declines were observed for both diets in serum prealbumin and retinol-binding protein concentrations. Mean serum transferrin declined with both diets, but the changes were not statistically significant. Serum albumin was unchanged by either diet. Thus, there were no significant differences between the two diets with regard to any of the measured parameters.
Metabolism, 1990
To study the influence of previous dietary protein depletion on nitrogen (N) loss and protein tur... more To study the influence of previous dietary protein depletion on nitrogen (N) loss and protein turnover during a total fast, we measured plasma leucine kinetics and urinary N and 3-methylhistidine (3MH) excretion in obese and normal subjects. In one study, 10 moderately obese women fasted for 2 weeks after adaptation either to a normal maintenance intake of 80 g protein and 150% of estimated resting energy expenditure (control group), or to 10 days of a 950-kcal, 200-g carbohydrate, 4-g protein diet (depletion group), with measurement of postabsorptive (or fasting) plasma leucine turnover on the maintenance diet and after 3 and 10 days of fasting. As measured after 10 days of fasting, body N loss was blunted by 17% when preceded by the protein-deficient diet. Plasma leucine flux and oxidation of the control group increased in early fasting and decreased by 10 days, in accordance with previous reports. Results for the depletion group were similar in absolute magnitude, despite the preceding protein-deficient diet. In a second study of five normal men, leucine kinetics were measured on a maintenance diet, after 10 days of a protein-free diet, and after 3 days of fasting. After protein depletion, leucine flux decreased by 19% (P less than .05). After 3 days fasting, leucine flux was 16% higher than on the maintenance diet (P less than .05), but 44% higher than the value on the protein-free diet 3 days earlier (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)