C. De Palo

Effect of licorice on the reduction of body fat mass in healthy subjects

The history of licorice, as a medicinal plant, is very old and has been used in many societies throughout the millennia. The active principle, glycyrrhetinic acid, is responsible for sodium retention and hypertension, which is the most common side-effect. We show an effect of licorice in reducing body fat mass. We studied 15 normalweight subjects (7 males, age 22–26 yr, and 8 females, age 21–26 yr), who consumed for 2 months 3.5 g a day of a commercial preparation of licorice. Body fat mass (BFM, expressed as percentage of total body weight, by skinfold thickness and by bioelectrical impedance analysis, BIA) and extracellular water (ECW, percentage of total body water, by BIA) were measured. Body mass index (BMI) did not change. ECW increased (males: 41.8±2.0 before vs 47.0±2.3 after, p<0.001; females: 48.2±1.4 before vs 49.4±2.1 after, p<0.05). BFM was reduced by licorice: (male: before 12.0±2.1 vs after 10.8±2.9%, p<0.02; female: before 24.9±5.1 vs after 22.1±5.4, p<0.02); plasma renin activity (PRA) and aldosterone were suppressed. Licorice was able to reduce body fat mass and to suppress aldosterone, without any change in BMI. Since the subjects were consuming the same amount of calories during the study, we suggest that licorice can reduce fat by inhibiting 11β-hydroxysteroid dehydrogenase Type 1 at the level of fat cells.

Plasma lactate, GH and GH-binding protein levels in exercise following BCAA supplementation in athletes

Summary. Branched chain amino acids (BCAA) stimulate protein synthesis, and growth hormone (GH) is a mediator in this process. A pre-exercise BCAA ingestion increases muscle BCAA uptake and use. Therefore after one month of chronic BCAA treatment (0.2 g kg−1 of body weight), the effects of a pre-exercise oral supplementation of BCAA (9.64 g) on the plasma lactate (La) were examined in triathletes, before and after 60 min of physical exercise (75% of VO2max). The plasma levels of GH (pGH) and of growth hormone binding protein (pGHBP) were also studied. The end-exercise La of each athlete was higher than basal. Furthermore, after the chronic BCAA treatment, these end-exercise levels were lower than before this treatment (8.6 ± 0.8 mmol L−1 after vs 12.8 ± 1.0 mmol L−1 before treatment; p < 0.05 [mean ± std. err.]). The end-exercise pGH of each athlete was higher than basal (p < 0.05). Furthermore, after the chronic treatment, this end-exercise pGH was higher (but not significantly, p = 0.08) than before this treatment (12.2 ± 2.0 ng mL−1 before vs 33.8 ± 13.6 ng mL−1 after treatment). The end-exercise pGHBP was higher than basal (p < 0.05); and after the BCAA chronic treatment, this end-exercise pGHBP was 738 ± 85 pmol L−1 before vs 1691 ± 555 pmol L−1 after. pGH/pGHBP ratio was unchanged in each athlete and between the groups, but a tendency to increase was observed at end-exercise.The lower La at the end of an intense muscular exercise may reflect an improvement of BCAA use, due to the BCAA chronic treatment. The chronic BCAA effects on pGH and pGHBP might suggest an improvement of muscle activity through protein synthesis.

Free carnitine and acetyl carnitine plasma levels and their relationship with body muscular mass in athletes

SummaryThe purpose of the present study was to investigate the relationship between plasma carnitine concentration and body composition variation in relation to muscular and fat masses since there is no experimentally proved correlation between plasma carnitine and body masses. We used bioelectric impedance analysis (BIA), to determine body composition and to have a complete physical fitness evaluation. The post-absorptive plasma free carnitine and acetyl carnitine plasma levels, body composition as Fat-Free Mass (FFM) and Fat Mass (FM) in kg, as well as in percent of body mass, were analysed in 33 healthy subjects. A significant negative correlation was found between plasma acetyl carnitine and FFM in weight (kg) as well as in percent of body mass (respectively p < 0.0001; p < 0.01); a significant positive correlation was found only between FM in percent and plasma acetyl carnitine (p < 0.01). The observed negative correlation between plasma acetyl carnitine and muscular mass variation might reflect an oxidative metabolic muscle improvement in relation to muscular fat free mass increment and might be evidence that muscle metabolism change is in relation to plasma acetyl carnitine concentration.

The effect of propranolol on hypoglycaemia: Observations in five insulinoma patients

SummaryFive hypoglycaemic hyperinsulinaemic patients (three with proven benign insulinoma, one with proven metastasizing insulinoma, one with probable insulinoma not found at surgery) were treated with propranolol for a variable time ranging from two weeks to one year. Three patients showed favourable clinical results and a significant increase of the mean basal blood glucose level was found while two patients showed no improvement of the frequency of neuroglycopenic episodes and no significant increase of their mean basal blood glucose level. No patient showed a significant decrease in mean basal IRI concentration.A decrease of insulinaemic responses was observed during oral and intravenous glucose tolerance tests, a prolonged fast, and tolbutamide and glucagon tests performed in some patients.The results suggest that propranolol may induce in certain patients an improvement of basal clinical status through not undestood effects (probably hepatic), which leave the peripheral concentrations of insulin unchanged, whereas inhibition of insulin secretion may represent the main way by which the improvement of metabolic situation during physiological or pharmacological stimulation may have been achieved.

Branched chain amino acids chronic treatment and muscular exercise performance in athletes: a study through plasma acetyl-carnitine levels

SummaryIn relation to energy request during physical exercise, muscular tissue Branched Chain Amino Acids (BCAA) are metabolized particularly when the oxidation rises. But in the whole-human body, it is difficult to estimate, in a quantitative sense, the role played by BCAA in sustaining exercise. During a BCAA treatment, made on a group of athletes kept under observation, it was observed, through Conconis test, that this treatment influenced physical performance. Aim of present work is to investigate if BCAA chronic treatment effect on physiological trial is confirmed on blood circulating biochemical energy parameters and in particular on acetyl-carnitine, since acetyl-linked compounds may be an important biochemical factor.Fourteen athletic well trained male subjects, were randomly divided into two subgroups; a first group was submitted to a chronic treatment (n = 7) of BCAA (oral intake was 0.2 g/Kg die) and a second group, as controls (n = 7), assumed oral placebo. Conconis test demonstrated a significant difference (p < 0.005) in the exercise performance of the two sub-groups, comparing the measurements of ratios of deflection velocity (Vd), before and after the treatment. Therefore we studied the athletes performing a muscular exercise test (40 Km/h, cycle race, for 90 min) after one month of treatment. During this treatment period the subjects followed a well standardized diet. Samples of blood were drawn before, at the end and during the recovery (60 min) to study if traditional biochemical parameters varied and confirmed the observed differences in Conconis test. The measurements of concentrations of FFA, KB, free carnitine, acetyl-carnitine and BCAA were performed. Plasma BCAA levels did not demonstrate variations either before or after the exercise performance, or between the two groups. The biochemical factors, substrates and hormones, KB, FFA, lactate, insulin and growth hormone plasma levels did not demonstrate significant differences from the patterns present in literature. Plasma free and acetyl-carnitine followed the well known variations, but only acetyl-carnitine levels demonstrated, at the end increase in acetyl-carnitine levels could be related to a minor fatigue situation and to a larger energy supply availability perhaps present in BCAA treated athletes (Sahlin et al., 1990; May et al., 1989). Both mentioned hypothesis seem in concordance with a smaller acetyl-CoA substrate accumulation, or better for present study, is even more successful with athletes who give a better physical performance. In fact Conconis test in the two sub-groups of athletes seems to suggest that BCAA treated athletes were able to give a better performance, furthermore out of curiosity we point out that the athletes treated with BCAA won more races than the untreated.We would also like to add in conclusion that although confirming the difficulties of studies in the whole-body, our work gives an interesting clue about the possibility to use acetyl-carnitine plasma levels to understand the biochemical importance of the BCAA as substrate able to influence physical performance, but further research is needed.The phenomenon presence might be showed better perhaps by studying untrained groups during prolonged exercise and with physical performance at exhaustion. If treatment were able to help the physical performance and to shift the fatigue, then confirmation might be a less raised plasma acetyl-carnitine level. In effect blood ammonium levels in present study did not demonstrate any variation in and between sub-groups; this latter observation could be caused by the quantity of work load, and training state of the athletes (Ji et al., 1987; Kirkendall, 1990). Moreover, as observed by Hageloch et al. (1990), the ammonia increases less during prolonged endurance exercise, and in fact the athletes of present study were all middle distance racing cyclists, and the physical performance was a prolonged endurance exercise.

Effect of exercise on plasma kallikrein and muscular phospholipase A2 activity in rats.

Many experimental observations show that prolonged physical exercise produces an increase of muscular glucose uptake. Recent findings suggest that the kallikrein-kinin-prostaglandin system may be related to this phenomenon, but so far, no direct evidence of quantitative alteration in this system has been observed during exercise. We measured plasma kallikrein and muscular phospholipase A2 activity, respectively the first and the last steps of reactions leading to prostaglandin synthesis. We demonstrated, for the first time, that during exercise plasma kallikrein activity increases in rats. We also observed an increase of muscular phospholipase A2 activity after exercise and a positive correlation between these parameters. Our findings demonstrate, under physiological conditions of enhanced muscular glucose uptake, a concomitant significant increase of plasma kallikrein and muscular phospholipase A2 activity, supporting the hypothesis that activation of the kallikrein-kinin-prostaglandin system may play some part in the enhanced muscular glucose uptake during physical activity.

Effect of portacaval shunt on circulating free fatty acids and ketone bodies in rats

To ascertain whether portal diversion affects ketone body (KB) metabolism, fasting circulating levels of free fatty acids (FFA), acetoacetate (AcAc) and B-hydroxybutyrate (3-OH-B) were measured in portacaval shunted (PCS), sham-operated (S-O) and unoperated control (C) rats. In PCS animals blood KB concentration was clearly reduced when compared with S-O and C rats. Beta-hydroxybutyrate level was significantly lower in PCS rats, whereas AcAc concentration did not appear significantly modified in these animals. The hypothesis is proposed that hypoketonemia induced by portal diversion is due to reduced hepatic availability of fatty acids.

Branched-chainα-amino acid chronic treatment: responses of plasmaα-keto-related compounds and ammonia when used in physical exercise performance.

SummaryTo examine the effects of acute branched-chainα-amino acids (BCAA) oral administration following chronic BCAA intake, a group of well trained young swimmers (n = 12) was submitted to a one month chronic BCAA treatment (0.2g/Kg body weight per die; Leu: Val: Ileu = 2:1:1) and a physical exercise test before and after this period of treatment was carried out. The exercise tests (60min swim) were performed in a high circulating BCAA level state which was obtained through oral BCAA administration (or placebo) just before the beginning of the exercise. The groups will be referred to as BCAA/before, BCAA/after, placebo/before, placebo/after. Blood and plasma (antecubital vein) samples were collected from the different groups at different times: on the morning of the day before the test (basal time, rest 0), the following day 30min after an acute administration (oral dose placebo or BCAA acute treatment: Leu 4.8g, Val 2.4g, Ileu 2.4g), just before the beginning of the exercise performance (time 0min, rest 1), at the end of the exercise (time 60min, EE) and during recovery (time 120min, Re). Plasma ammonia levels increased significantly from rest 1 to the end of the exercise in all subjects, but it was significantly higher in BCAA treated than in placebo subjects in both the before and after chronic treatment groups (BCAA/before: from 38 ± 7 to 204 ± 65mmol/l; placebo/before: from 36 ± 10 to 93 ± 29mmol/l; BCAA/after: from 36 ± 9 to 171 ± 43mmol/l; placebo/after: from 30 ± 6 to 65 ± 16mmol/l). Plasma ammonia level increments observed before a chronic one month BCAA treatment were significantly higher than after this treatment (p < 0.05). Plasma alanine was at all times of the test higher before the BCAA chronic treatment than after; this difference resulted significant at rest 0, rest 1 and recovery times (p < 0.05). After acute BCAA administration, plasma BCAA levels increased from 618 ± 52mmol/l to 1893 ± 284mmol/l (p < 0.05) from the onset of exercise and remained elevated throughout the test. Placebo and basal (rest 0) levels both before and after the chronic treatment did not demonstrate any significant differences. Plasma BCAA and BCKA levels, in the BCAA/before demonstrated significantly higher levels than placebo/before at rest 1 time (BCAA/before vs placebo/before: Leu 86 ± 27 vs 620 ± 97mmol/l; KIC 60 ± 3 vs 87 ± 5mmol/l, Ileu 51 ± 19 vs 359 ± 56mmol/l, KMV 26 ± 1 vs 43 ± 2mmol/l, Val 290 ± 79 vs 915 ± 133mmol/l, KIV 14 ± 1 vs 24 ± 2mmol/l). The levels after the chronic treatment maintained circa these differences in the two groups BCAA/after and placebo/after. The plasma BCAA as well as the BCKA levels of acutely treated athletes, in physical exercise, showed a different profile before and after the chronic treatment. The chronic treated BCAA/after group in fact depicted a decreasing BCKA level profile at the end of the exercise and during recovery; on the contrary, before the chronic treatments, acutely treated athletes demonstrated a tendency to increase these levels during recovery. These data seem to confirm that increased BCAA availability, before exercise, result in significantly greater plasma ammonia responses during exercise than does placebo administration; furthermore this increment is lower after chronic treatment. The interpretation of the ammonia data is difficult since the exercise type could have an influence on this phenomenon. The differences in the profile patterns of alanine, BCAA and BCKA levels seem to indicate that the chronic treatment brings about a state in which there is a better use of BCAA compounds as energy supply.

Plasma Acetyl-Carnitine Concentrations during and after a Muscular Exercise Test in Patients with Liver Disease

In many human tissues, fuel is stored for immediate use, as well as for energy exchange between different parts of the body. Fat and glycogen represent, together with proteins, the principal energy storage materials. During energy requirement, e.g. muscular exercise, glycogen as a local reserve, is used first to supply energy needs. Acetyl-carnitine, as an active molecular group, represents an intermediate substrate, usable directly in the working tissue. The present study investigates whether plasma acetyl-carnitine could be a useful biochemical measure for information on fuel exchange in the body, and whether it is a rapidly available energy source exchangeable among tissues with different metabolic functions, such as muscle and liver. The present study investigated control and hepatopathic subjects after maximal and submaximal muscular exercise. Hepatopathic patients may be a useful model, as liver carnitine metabolism is likely to be impaired. Plasma acetyl-carnitine before, during and after maximal exercise in hepatopathic subjects did not differ, while in normal subjects it increased. After submaximal exercise, acetyl-carnitine increased in patients, as well in controls. In the patients (n = 9) with liver metabolism disorders we observed that during maximal exercise plasma acetyl-carnitine varied from 3.26 +/- 2.18 mumol/l (time 0 min) to 4.30 +/- 2.02 mumol/l (time 20 min) and from 1.99 +/- 1.36 mumol/l to 4.83 +/- 2.60 mumol/l (p less than 0.05) in the controls (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrine pancreatic function in pheochromocytoma

In six patients with pheochromocytoma oral glucose tolerance test (OGTT) and arginine test were carried out. Blood insulin and glucagon response were investigated. In subjects with adrenal tumor glycemic curve pattern was typical: a rapid and exaggerated increase of glycemia followed by an abrupt drop. Absolute insulinemic response to oral glucose was normal, but inappropriate to glycemic stimulus. Arginine infusion provoked a slightly above normal increase in blood glucose and a normal increase in blood glucagon. In three of the patients studied postoperatively, reduced glycemic response to glucose was observed, whereas there were no evident variations in blood insulin and glucagon response. These data suggest that in pheochromocytoma impaired glucose tolerance is partly due to the reduced insulin response to oral glucose load.