Changes In Dietary Carbohydrate Research Articles

Changes in dietary carbohydrate and lipid quality indices between 2008 and 2018: Analysis of the Brazilian dietary surveys.

The aim of the study was to evaluate characteristics and changes over a decade in dietary carbohydrate and lipid quality according to socio-demographic variables. Data was obtained from two Brazilian National Dietary Surveys 2008-2009 (n = 34 003) and 2017-2018 (n = 46 164) examining a nationwide representative sample of individuals ≥10 years old. Food intake was assessed by means of two non-consecutive diet records (2008-2009) and 24 h diet recalls (2017-2018). Carbohydrate Quality Index is a score ranging from 4 to 20 calculated from fibre intake, global dietary glycaemic index, solid/total carbohydrate (CHO) and whole grains/total grains CHO. Lipid Quality Index was estimated by dividing the sum of the dietary content of monounsaturated and polyunsaturated fatty acids by the sum of saturated and trans fatty acids. Indices were categorised into five categories (1 for lowest and 5 for highest quality). Socio-demographic variables were sex, age, income, urban/rural area and place of food consumption. The estimates (95% CI) were generated separately for each survey and then compared to identify changes in time. Our main findings refer to changes in diet quality according to income. At the lowest income level, the proportions of individuals in the best carbohydrate and lipid quality categories reduced from 26.9% to 20.6% and from 30.0% to 24.9%, respectively. Alternatively, at the highest income level, these proportions increased from 22.9% to 26.6% and from 11.9% to 15.7%, respectively. Furthermore, the quality of lipids improved in women and among individuals reporting some away-from-home food consumption, while the quality of carbohydrates was reduced among adolescents and in rural areas.

Effects of short-term graded dietary carbohydrate intake on intramuscular and whole body metabolism during moderate-intensity exercise.

Altering dietary carbohydrate (CHO) intake modulates fuel utilization during exercise. However, there has been no systematic evaluation of metabolic responses to graded changes in short-term (< 1 wk) dietary CHO intake. Thirteen active men performed interval running exercise combined with isocaloric diets over 3 days before evaluation of metabolic responses to 60-min running at 65% V̇O2max on three occasions. Diets contained lower [LOW, 2.40 ± 0.66 g CHO·kg-1·day-1, 21.3 ± 0.5% of energy intake (EI)], moderate (MOD, 4.98 ± 1.31 g CHO·kg-1·day-1, 46.3 ± 0.7% EI), or higher (HIGH, 6.48 ± 1.56 g CHO·kg-1·day-1, 60.5 ± 1.6% EI) CHO. Preexercise muscle glycogen content was lower in LOW [54.3 ± 26.4 mmol·kg-1 wet weight (ww)] compared with MOD (82.6 ± 18.8 mmol·kg-1 ww) and HIGH (80.4 ± 26.0 mmol·kg-1 ww, P < 0.001; MOD vs. HIGH, P = 0.85). Whole body substrate oxidation, systemic responses, and muscle substrate utilization during exercise indicated increased fat and decreased CHO metabolism in LOW [respiratory exchange ratio (RER): 0.81 ± 0.01] compared with MOD (RER 0.86 ± 0.01, P = 0.0005) and HIGH (RER: 0.88 ± 0.01, P < 0.0001; MOD vs. HIGH, P = 0.14). Higher basal muscle expression of genes encoding proteins implicated in fat utilization was observed in LOW. In conclusion, muscle glycogen availability and subsequent metabolic responses to exercise were resistant to increases in dietary CHO intake from ∼5.0 to ∼6.5 g CHO·kg-1·day-1 (46% to 61% EI), while muscle glycogen, gene expression, and metabolic responses were sensitive to more marked reductions in CHO intake (∼2.4 g CHO·kg-1·day-1, ∼21% EI).NEW & NOTEWORTHY The data presented here suggest that metabolic responses to steady-state aerobic exercise are somewhat resistant to short-term changes in dietary carbohydrate (CHO) intake within the 5-6.5 g CHO·kg-1·day-1 [46-61% energy intake (EI)] range. In contrast, reduction in short-term dietary CHO intake to ∼2.4 g CHO·kg-1·day-1 (21% EI) evoked clear changes indicative of increased fat and decreased CHO metabolism during exercise.

Trehalose metabolism confers developmental robustness and stability in Drosophila by regulating glucose homeostasis

Organisms have evolved molecular mechanisms to ensure consistent and invariant phenotypes in the face of environmental fluctuations. Developmental homeostasis is determined by two factors: robustness, which buffers against environmental variations; and developmental stability, which buffers against intrinsic random variations. However, our understanding of these noise-buffering mechanisms remains incomplete. Here, we showed that appropriate glycemic control confers developmental homeostasis in the fruit fly Drosophila. We found that circulating glucose levels are buffered by trehalose metabolism, which acts as a glucose sink in circulation. Furthermore, mutations in trehalose synthesis enzyme (Tps1) increased the among-individual and within-individual variations in wing size. Whereas wild-type flies were largely resistant to changes in dietary carbohydrate and protein levels, Tps1 mutants experienced significant disruptions in developmental homeostasis in response to dietary stress. These results demonstrate that glucose homeostasis against dietary stress is crucial for developmental homeostasis.

Molecular characterization and expression analysis of glucose transporter 1 and hepatic glycolytic enzymes activities from herbivorous fish Ctenopharyngodon idellus in respond to a glucose load after the adaptation to dietary carbohydrate levels

In the present study, we test the hypothesis that the ability of Ctenopharyngodon idellu to clear a glucose load is related to nutrient history of different dietary carbohydrate through the transport and glycolysis of glucose. Firstly, we obtained the complete coding sequence from C. idellus GLUT1 (ciGLUT1), composed by 2364 bp with an open reading frame of 1473 bp encoding 490 amino acids. Sequence alignment and phylogenetic analysis revealed a high degree of conservation (80–97%) among most fish and higher vertebrates. The analysis of the 5′ and 3′ UTRs showed the presence of several post-transcriptional regulatory elements. The highest ciGLUT1 expression was observed in the heart followed by brain, whereas relatively low values were detected in the muscle, gill, intestine, kidney, spleen and liver. Then, hepatic and intestine ciGLUT1 expressions and hepatic glycolytic enzymes activities were determined in fish subjected to a glucose load after being fed different dietary carbohydrate levels (20%, 40% and 60%) for 8 weeks. And the result showed that different dietary carbohydrate had no effect on ciGLUT1 mRNA of hepatic and intestine after 8 weeks trail. However, after the adaptation of carbohydrate levels, glucose administration caused a prompt increase of hepatic ciGLUT1 mRNA expressions in all treatments whereas it either had no effect or a negative effect on intestine ciGLUT1 mRNA. In terms of dietary carbohydrate levels, the ciGLUT1 expressions of fish fed high carbohydrate diet (60%) were significantly higher than the other groups after the glucose load. In additon, after the glucose administration, hepatic low Km hexokinases (HK) activities of fish fed high carbohydrate diets increased significantly and was also significantly higher than the other groups. The results indicated that the GLUT1 gene of C. idellus showed a typical structure of the glucose transporters family, supporting the concept that ciGLUT1 functions as a ubiquitous and constitutive basal level glucose transporter. Consistent with the function of the GLUT1 as a constitutive glucose transporter, ciGLUT1 expressions of hepatic and intestine were hardly affected by the changes in dietary carbohydrate. Furthermore, after the glucose load, the fish after a long-term high dietary carbohydrate adaptation showed a more efficient clearance of glucose through the more remarkable enhancements of hepatic ciGLUT1 expressions and HK activities.

Abstract P220: Elevated De Novo Lipogenesis Fatty Acids and Lower Omega-6 Fatty Acids Are Associated With Markers of Insulin Resistance and Respond to Changes in Dietary Carbohydrate Intake in Overweight Individuals on Weight Loss Diets

Background: High blood levels of certain fatty acids (FAs) in the de novo lipogenesis pathway (DNL; i.e., 16:0, cis-16:1n7) and low levels of omega-6 FAs (n-6 FA; i.e., 18:2n6) have been related to increased risk for type 2 diabetes. We hypothesized that individuals with insulin resistance (IR) would have higher DNL and lower n-6 FA plasma levels than insulin sensitive (IS) individuals, and that DNL FA levels would decrease on a low-carbohydrate (LC) diet and not change on a low-fat (LF) diet. Methods: Plasma FAs were measured as a % of total FA in subjects (n=61) with varying degrees of obesity and IR before and after 6 months of LF or LC weight loss diets. IR metrics were calculated pre- and post from oral glucose tolerance tests and fasting blood samples. FA medians (Interquartile Range), Spearman correlations (R) and Mann-Whitney test results are presented. Results: All differences shown are significant at P&lt;0.05 unless reported as not significant (NS). Compared to the IS group, IR individuals had higher 16:0 (IR: 22.9% [22.2, 24.3] vs IS: 21.7% [20.2, 22.5]) and 16:1n7 (IR: 1.8% [1.4, 2.2] vs IS: 1.3% [1.1, 1.6]), and lower 18:2n6 (IR: 30.8% [27.8, 31.6] vs IS: 32.5% [30.0, 34.6]) levels at baseline. 16:0 and 16:1n7 were directly related to BMI (0.40, 0.28), fasting insulin (0.40, 0.33), HOMA-IR (0.40, 0.43), TG:HDL (0.38, NS) and indirectly to Matsuda Index (-0.35, -0.34). 18:2n6 was directly related to the Matsuda Index (0.35) and indirectly to HOMA-IR (-0.37) and TG:HDL (-0.45). Diet x IR status analyses were not significant, thus FA changes on LC and LF diets were compared. 16:1n7 decreased on the LC diet and did not change on the LF diet (LC: -0.5% [-0.7, -0.3] vs LF: -0.1% [-0.3, 0.2]). 18:2n6 levels increased on the LC diet and decreased on the LF diet (LC: 0.9% [-0.3, 2.7] vs LF: -0.5% [-2.4, 0.6]). Changes in dietary carbohydrate (% of calories) correlated with changes in 16:1n7 directly (0.38) and 18:2n6 indirectly (-0.37). Changes in 16:1n7 were directly related to changes in weight (0.55) and TG:HDL (0.65), and changes in 18:2n6 were indirectly related to TG:HDL changes (-0.51). Conclusions: Elevated plasma DNL FA and lower 18:2n6 were evident in IR vs. IS individuals, and individual markers of IR were related to FA levels accordingly. DNL and 18:2n-6 responded to changes in carbohydrate intake. FA patterns may be a useful tool to identify IR individuals and track carbohydrate consumption.

Macronutrient Composition and Increased Physical Activity Modulate Plasma Adipokines and Appetite Hormones during a Weight Loss Intervention

We have shown previously that in overweight premenopausal women, changes in macronutrient composition and increasing the number of steps walked per day favorably affect body composition and plasma lipid profiles. As a follow-up, we evaluated the effect of moderate carbohydrate intake and increased physical activity on inflammation and regulation of appetite. Seventy premenopausal women with a body mass index (BMI) between 25 and 37 kg/m(2) participated in a 10-week weight loss intervention program consisting of the following macronutrient energy distribution: 40% carbohydrate, 30% fat, and 30% protein, in addition to a progressive increase in the number of steps taken per day. Plasma adiponectin, intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), leptin, and ghrelin levels were assessed at baseline and after 10 weeks. Subjects reduced body weight by 4.5%, waist circumference (WC) by 6.4%, and trunk fat by 4.6%. Plasma insulin and insulin resistance assessed by homeostasis model assessment (HOMA) were reduced after 10 weeks (p < 0.01). Plasma adiponectin was increased by 11% (p < 0.05), and ICAM-1 levels were decreased (p < 0.05) after 10 weeks. A negative correlation was found between changes in insulin and changes in adiponectin between baseline and 10 weeks (r = -0.397, p < 0.01), indicating a role of adiponectin in increasing insulin sensitivity. In addition, plasma ghrelin levels were increased by 17% (p < 0.001), indicating a signal for increased appetite associated with weight loss. These studies indicate that weight loss interventions involving moderate changes in dietary carbohydrate and increases in physical activity favorably affect insulin sensitivity and decrease inflammation.

Nonequilibrium thermodynamics and energy efficiency in weight loss diets.

Carbohydrate restriction as a strategy for control of obesity is based on two effects: a behavioral effect, spontaneous reduction in caloric intake and a metabolic effect, an apparent reduction in energy efficiency, greater weight loss per calorie consumed. Variable energy efficiency is established in many contexts (hormonal imbalance, weight regain and knock-out experiments in animal models), but in the area of the effect of macronutrient composition on weight loss, controversy remains. Resistance to the idea comes from a perception that variable weight loss on isocaloric diets would somehow violate the laws of thermodynamics, that is, only caloric intake is important ("a calorie is a calorie"). Previous explanations of how the phenomenon occurs, based on equilibrium thermodynamics, emphasized the inefficiencies introduced by substrate cycling and requirements for increased gluconeogenesis. Living systems, however, are maintained far from equilibrium, and metabolism is controlled by the regulation of the rates of enzymatic reactions. The principles of nonequilibrium thermodynamics which emphasize kinetic fluxes as well as thermodynamic forces should therefore also be considered.Here we review the principles of nonequilibrium thermodynamics and provide an approach to the problem of maintenance and change in body mass by recasting the problem of TAG accumulation and breakdown in the adipocyte in the language of nonequilibrium thermodynamics. We describe adipocyte physiology in terms of cycling between an efficient storage mode and a dissipative mode. Experimentally, this is measured in the rate of fatty acid flux and fatty acid oxidation. Hormonal levels controlled by changes in dietary carbohydrate regulate the relative contributions of the efficient and dissipative parts of the cycle. While no experiment exists that measures all relevant variables, the model is supported by evidence in the literature that 1) dietary carbohydrate, via its effect on hormone levels controls fatty acid flux and oxidation, 2) the rate of lipolysis is a primary target of insulin, postprandial, and 3) chronic carbohydrate-restricted diets reduce the levels of plasma TAG in response to a single meal.In summary, we propose that, in isocaloric diets of different macronutrient composition, there is variable flux of stored TAG controlled by the kinetic effects of insulin and other hormones. Because the fatty acid-TAG cycle never comes to equilibrium, net gain or loss is possible. The greater weight loss on carbohydrate restricted diets, popularly referred to as metabolic advantage can thus be understood in terms of the principles of nonequilibrium thermodynamics and is a consequence of the dynamic nature of bioenergetics where it is important to consider kinetic as well as thermodynamic variables.

SCFA increase intestinal Na absorption by induction of NHE3 in rat colon and human intestinal C2/bbe cells.

Short-chain fatty acids (SCFA), produced by colonic bacterial flora fermentation of dietary carbohydrates, promote colonic Na absorption through mechanisms not well understood. We hypothesized that SCFA promote increased expression of apical membrane Na/H exchange (NHE), serving as luminal physiological cues for regulating colonic Na absorptive capacity. Studies were performed in human colonic C2/bbe (C2) monolayers and in vivo. In C2 cells exposed to butyrate, acetate, proprionate, or the poorly metabolized SCFA isobutyrate, apical membrane NHE3 activity and protein expression increased in a time- and concentration-dependent manner, whereas no changes were observed for NHE2. In contrast, no significant changes in brush-border hydrolase or villin expression were noted. Analogous to the in vitro findings, rats fed the soluble fiber pectin exhibited a time-dependent increase in colonic NHE3, but not NHE2, protein, mRNA, and brush-border activity. These changes were region-specific, as no changes were observed in the ileum. We conclude that luminal SCFA are important physiological cues for regulating colonic Na absorptive function, allowing the colon to adapt to chronic changes in dietary carbohydrate and Na loads.

Carbohydrate intake and short-term regulation of leptin in humans.

The response of serum leptin to short (4 days) and prolonged (28 days) energy restriction (50% reduction in energy intake) was determined in 18 (9 male, 9 female) moderately obese humans (body mass index 32.0 +/- 0.6 kg/m2 mean +/- SEM), 9 of whom had mild non-insulin-dependent diabetes mellitus (NIDDM). Body composition was assessed before and at the end of the energy restriction using DEXA. The subjects lost a measured 2.6 +/- 0.4 kg of body fat after 28 days and an estimated 0.3 kg at 4 days. Serum leptin fell to 64 +/- 3% of baseline levels at day 4 and further to 46 +/- 4% at day 28. In a multiple correlation analysis, the change in leptin concentration at day 4 was significantly related to the change in dietary carbohydrate intake (partial r = 0.68, p < 0.005) but not to changes in fat (r = 0.12) or protein (r = 0.02) intakes. There was a 1:1 relationship between the changes in leptin and dietary carbohydrate (regression slope = 1.0 +/- 0.3). Gender, or the presence of NIDDM had no effects on these responses. This pronounced fall in serum leptin in association with reduced carbohydrate intake before substantial loss of body fat suggests a role for leptin in defending the body's carbohydrate stores and implicates leptin in the satiating effects of carbohydrate. Dietary or other interventions which maintain leptin levels during weight reduction may lead to improvements in weight loss.

Lipoprotein lipase activities in exercise-trained rats isocalorically fed high or low fat diets

Influences of exercise and changes in dietary carbohydrate and fat on tissue lipoprotein lipase (LPL) activities were studied in 40 female Sprague-Dawley rats. Rats were trained to run (n=20) on a treadmill 6 days/week, 60 minutes/day at 28 m/min on an 8° incline for 8 wk or remained sedentary (n=20). All rats were fed a control high carbohydrate diet (12% kcals fat) for 5 weeks and then one-half of the trained and nontrained groups were assigned to a high fat (HF) diet. The HF (73% kcals fat) fed rats were pair fed to be isocaloric and isonitrogenous with the animals receiving the control diet. Animals were fasted 12–14 hours before sacrifice. Feeding the HF diet increased body weight, fat pad weight and plasma TG levels, but had no effect on muscle weight or muscle TG content. Training at least doubled the LPL activivity of the red gastrocnemius muscle. The combination of HF feeding and exercise produced an elevation in the LPL activity of the red (135%) and white (80%) gastrocnemius muscles compared to control feeding and no exercise. The additive effect of the HF diet and exercise training also increased LPL activity of renal adipose tissue (43%) versus control feeding and no exercise. Feeding the HF diet reduced glycogen depletion in liver and skeletal muscle during exercise. This study demonstrates that skeletal muscle LPL activity is sensitive to the individual and combined effects of dietary fat and exercise.

Intestinal adaptations of rainbow trout to changes in dietary carbohydrate.

Although omnivores are able to alter the structure and functions of their digestive system in response to changes in dietary carbohydrate content, it is unclear whether carnivores are capable of such adaptive flexibility. Hence we recorded growth rates, intestinal morphometrics and histology, and nutrient uptake rates and concentrations of disaccharidases in the intestines of a carnivorous fish, the rainbow trout, fed different levels and types of carbohydrate. The trout is unable to adaptively regulate digestive system structure and function to increase glucose availability in response to increasing levels of dietary carbohydrates, even to easily digestible forms such as glucose. Paradoxically, a reduction in the concentrations of enzymes associated with carbohydrate digestion in response to elevated levels of easily digested carbohydrates suggests that carnivores may actually try to repress carbohydrate digestion when glucose is available in high quantities. Thus the lower levels of carbohydrate in the diet of trout throughout their evolution has resulted in a reduced ability to phenotypically regulate the digestion of carbohydrates.

Divergent responses of serum lipoproteins to changes in dietary carbohydrate and cholesterol in cynomolgus monkeys

The metabolic effects of dietary carbohydrates (simple versus complex) on lipogenesis, glucose, and insulin responses are well known, but information is lacking on the effect of carbohydrate types on different serum lipoprotein fractions. We therefore studied the differences in responses of serum lipids, lipoproteins, apoproteins, and plasma glucose and insulin to changes in dietary carbohydrates and cholesterol in 12 male cynomolgus monkeys ( Macaca fascicularis). For 6 weeks, each monkey was fed one of four semipurified, high-carbohydrate (76.5% cal) diets that provided sucrose or starch with and without 1 mg/kcal cholesterol. Sucrose diet without added cholesterol resulted in consistently higher serum total cholesterol than with a similar starch diet. In contrast, cholesterol-enriched starch diet caused marked increase in serum total cholesterol when compared to similar sucrose diet. Neither starch nor sucrose diets elicited a VLDL-triglyceride response. Observations on apoB, VLDL- and LDL-cholesterol levels essentially reflected serum total cholesterol changes by diet. Changes in HDL-subfractions to dietary carbohydrates were seen mainly in HDL 2, with starch producing lower values than sucrose ( p < 0.01). Among the four diets, cholesterol, triglyceride and phospholipid contents of HDL 2, as well as apoA-I and apoA-II contents of serum total lipoproteins were lowest with cholesterol-enriched starch diet feeding. High cholesterol diets increased the cholesterol to triglyceride ratios of LDL, irrespective of type of carbohydrate ( p < 0.01), whereas the ratios of cholesterol to phospholipids showed significant carbohydrate effect (starch > sucrose) and cholesterol effect for HDL 2. Neither plasma glucose nor insulin showed any diet-related differences. Thus, a high level of dietary carbohydrate with and without added cholesterol provoked divergent responses of serum lipids and lipoproteins between sucrose and starch. Although reasons for the paradoxical responses are not readily apparent, the experiment provides a useful model for further metabolic studies.

Effects of dietary carbohydrate and fat on plasma lipoproteins and apolipoproteins C-II and C-III in healthy men

Effects of isocaloric changes in dietary fat and carbohydrate on plasma apolipoproteins (apo) C-II, C-III, and lipoproteins were assessed in nine healthy men. Carbohydrate and fat comprised 80% of total calories. After a 1-week basal diet (40% of calories from carbohydrate), the subjects received either a high (65% of calories) or low (15% of calories) carbohydrate diet for 3 weeks; subsequently the diets were switched, those initially on high carbohydrate going on to low carbohydrate, and vice versa, and the new diets were maintained for 3 weeks. ApoC-II, C-III, and triglycerides initially rose and then declined during the high carbohydrate diet period; high density lipoprotein cholesterol (HDL-C) decreased. Comparing results after 3 weeks of high carbohydrate diet to those after 3 weeks on low carbohydrate, we observed the following significant differences: 1) total plasma apoC-II and C-III were higher; the apoC-III/C-II ratio in very low density lipoproteins (VLDL) and in the lighter HDL subfraction (HDL2) was lower indicating net lipoprotein enrichment with apoC-II than with apoC-III; 2) unsialylated apoC-III0 comprised a higher percent of total VLDL apoC-III mass; 3) HDL2 and HDL2/HDL3 ratio were lower. Isocaloric changes in dietary carbohydrate and fat cause significant alterations in plasma levels of VLDL and HDL 2, the two major lipoproteins that transport apoC-III and apoC-II. Diet-induced changes in circulating apoC-III and C-II may, in part, play a role in regulation of plasma triglycerides in man.

Effect of Carbohydrate and Noncarbohydrate Sources of Calories on Plasma 3,5,3′-Triiodothyronine Concentrations in Man*

ABSTRACT To evaluate the effect of changes in dietary carbohydrate (CHO) and excessive caloric consumption on circulating thyroid hormone levels, six normal weight subjects were fed five separate diets: three isocaloric diets with 20%, 40%, or 80% CHO and two hypercaloric (+2000 calories) diets with 20% or 40% CHO for 5 days each as outpatients. T4, T3, and rT3 concentrations were measured in plasma samples collected on the morning of the sixth day. At least 1 week of the subjects' usual diets intervened between each experimental diet. Mean T4 and rT3 levels were similar after all diets. Pair-wise comparisons among all five diets revealed significantly (P < 0.005) increased T3 concentrations after both hypercaloric diets compared to the iso-20 and iso-40 diets, and after the iso-80 compared to the iso-20 diet. A multiple regression analysis of the data revealed the highest correlation of T3 levels with total calories (r = 0.68; P < 0.001) rather than with the intake of CHO (r = 0.46; P < 0.025), fat (r = ...

Influence of dietary protein and carbohydrate on antipyrine and theophylline metabolism in man

This study was undertaken to examine the influence of changes in dietary carbohydrate and protein content on the oxidation of antipyrine and theophylline in man. When the diets of 6 normal volunteers were changed from their usual home diets to low carbohydrate-high protein diets, the plasma half-life of antipyrine decreased from 16.2 hr to 9.5 hr, and the half-life of theophylline decreased from 8.1 hr to 5.2 hr. When the subjects' diets were changed from low carbohydrate-high protein diets to a high carbohydrate-low protein diets, the mean antipyrine half-life increased from 9.5 hr to 15.6 hr and the mean theophylline half-life increased from 5.2 hr to 7.6 hr. These changes in half-lives were accompanied by changes in metabolic clearance rates but not in the apparent volumes of distribution of the drugs tested. Qualitatively similar results were obtained when the subjects were placed on standard diets followed by the standard diets supplemented with carbohydrate or protein. Supplementing the standard diets with carbohydrate caused an increase in drug half-lives, whereas a protein supplement caused a decrease in the drug half-lives. These data demonstrate marked influences of nutritional factors on oxidative biotransformation of drugs in man.

Effect of caloric restriction and dietary composition of serum T3 and reverse T3 in man.

To evaluate the effect of caloric restriction and dietary composition on circulating T3 and rT3 obese subjects were studied after 7-18 days of total fasting and while on randomized hypocaloric diets (800 kcal) in which carbohydrate content was varied to provide from 0 to 100% calories. As anticipated, total fasting resulted in a 53% reduction in serum T3 in association with reciprocal 58% increase in rT3. Subjects receiving the no-carbohydrate hypocaloric diets for two weeks demonstrated a similar 47% decline in serum T3 but there was no significant change in rT3 with time. In contrast, the same subjects receiving isocaloric diets containing at least 50 g of carbohydrate showed no significant changes in either T3 or rT3 concentration. The decline in serum T3 during the no-carbohydrate diet correlated significantly with blood glucose and ketones but there was no correlation with insulin or glucagon. We conclude that dietary carbohydrate is an important regulatory factor in T3 production in man. In contrast, rT3 concentration is not significantly affected by changes in dietary carbohydrate. Our data suggest that the rise in serum rT3 during starvation may be related to more severe caloric restriction than that caused by the 800 kcal diet.