Biomedical subjects
A Laviano
Publications and source records attributed to A Laviano.
Food intake equals meal size times mean number.
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Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients.
OBJECTIVE: In obese patients, brain serotonergic stimulation via orally administered 5-hydroxy-tryptophan (5-HTP), the precursor of serotonin, causes decreased carbohydrate intake and weight loss. Since diabetes mellitus is associated with depressed brain serotonin, hyperphagia and carbohydrate craving, we hypothesized that in diabetic patients, orally administered 5-HTP stimulates brain serotonergic activity and thus normalizes eating behaviour. To test this hypothesis, we investigated whether in diabetic patients: 1) predicted brain serotonin concentrations are depressed as a result of decreased availability of the precursor, tryptophan; and 2) oral 5-HTP is effective in reducing energy and carbohydrate intake. SUBJECTS AND METHODS: 25 overweight non-insulin dependent diabetic outpatients were enrolled in a double-blind, placebo-controlled study, and randomized to receive either 5-HTP (750 mg/d) or placebo for two consecutive weeks, during which no dietary restriction was prescribed. Energy intake and eating behaviour, as expressed by macronutrient selection, were evaluated using a daily diet diary. Plasma amino acid concentrations and body weight, as well as serum glucose, insulin and glycosylated haemoglobin were assessed. RESULTS: 20 patients (nine from the 5-HTP group and 11 from the Placebo group) completed the study. Brain tryptophan availability in diabetic patients was significantly reduced when compared to a group of healthy controls. Patients receiving 5-HTP significantly decreased their daily energy intake, by reducing carbohydrate and fat intake, and reduced their body weight. CONCLUSIONS: These data confirm the role of the serotonergic system in reducing energy intake, by predominantly inhibiting carbohydrate intake, and suggest that 5-HTP may be safely utilized to improve the compliance to dietary prescriptions in non-insulin dependent diabetes mellitus.
Acute adaptive changes in food intake pattern following olfactory ablation in rats.
We determined whether acute compensatory feeding pattern changes after bulbectomy persist on a chronic basis, or whether physiological adaptation occurs to normalize acute changes. Rats were randomized to olfactory bulbectomy or sham operation; all had jugular vein catheterization. Food intake, meal number and size were studied during infusion of parenteral nutrients providing 100% daily caloric intake (PN-100) to minimize post-ingestive effects. Rats were randomly assigned to acute (from day 14 after operation, PN-100 infused for 4 days, followed by 4 days of saline infusion) or chronic study (PN-100 infused for 4 days from day 40, followed by 4 days of saline infusion). After olfactory ablation, acutely decreased meal size was offset by increased meal number, but 40 days after, baseline differences between meal size and number no longer existed. No qualitative differences in response to PN-100 were noted between acute and chronic groups. Findings suggest a functional adaptation of food intake regulatory mechanism between 14 and 40 days after bulbectomy.
Plasma tryptophan levels and anorexia in liver cirrhosis.
OBJECTIVE: Increased brain tryptophan (TRP) availability for serotonin synthesis may play a role in the pathogenesis of anorexia. Since in chronic liver failure, increased plasma and cerebrospinal fluid TRP concentrations are characteristically reported, we hypothesize that also in liver cirrhosis increased brain TRP availability may constitute the pathogenic mechanism of anorexia. To test this hypothesis, the association between anorexia and plasma TRP was investigated. METHODS: Anorexia and plasma amino acid concentrations were evaluated in 16 patients with liver cirrhosis and compared with those obtained in 13 healthy volunteers. RESULTS: According to a questionnaire, 11 cirrhotic patients were considered as anorectic. In these patients, brain TRP availability was significantly higher than in nonanorectic patients and controls. DISCUSSION: Increased brain TRP availability is also associated with anorexia in liver cirrhosis, and supports the hypothesis that increased serotonergic activity may constitute the common pathogenic mechanism for anorexia associated with different diseases.
Pathogenesis of cancer anorexia: personal perspective.
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Meal size and number: relationship to dopamine levels in the ventromedial hypothalamic nucleus.
Evidence shows a reciprocal relationship exists between the lateral hypothalamic area (LHA) and the ventromedial hypothalamic nucleus (VMN) in food intake regulation. Since a direct correlation between meal size and LHA-dopamine in Fischer rats was previously reported, we tested the hypothesis that an inverse association may exist between meal size and VMN-dopamine response. This was studied in awake 24-h food-deprived rats who were then allowed to eat freely for 20 min while the VMN-dopamine response was measured by microdialysis every 20 min for 2 h. In a second experiment, only one-half the amount freely eaten was provided during microdialysis. The following were observed. 1) Dopamine concentrations in VMN decreased during eating. 2) The degree and duration of decrease after the meal corresponded to the size of the meal. 3) When the decreased postmeal VMN-dopamine level had returned to baseline and food was available, rats ate once more. The findings show that, in normal rats, eating was associated with decreased dopamine levels in the VMN and was followed by a lag time during which no additional eating occurred. VMN dopamine levels thereby contribute to determining the duration of the intermeal interval and hence, by inference, the meal number.
Effects of administration of oral branched-chain amino acids on anorexia and caloric intake in cancer patients.
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Serotoninergic block in the ventromedial nucleus of hypothalamus improves food intake in anorectic tumor bearing rats.
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Carnitine supplementation accelerates normalization of food intake depressed during TPN.
When total parenteral nutrition (TPN; containing glucose, fat, and amino acids; caloric ratio 50:30:20) providing 100% of the rat's daily caloric intake is given for 3-4 days, food intake rapidly decreases by approximately 85%. After stopping TPN, there is a lag period of 3-4 days before food intake returns to previous level, which appears to be related to fatty acid oxidation and fat deposition. Carnitine plays a key role in the oxidation of fatty acids, and was demonstrated to reduce fat deposition in rats receiving TPN, by increasing beta oxidation. We therefore investigated whether rats receiving TPN supplemented with carnitine may prevent either the decrease or speed up the resumption or normalization of food intake, after TPN is stopped. Fourteen adult Fischer-344 rats had a central venous catheter inserted. After 10 recovery days, controls (n = 7) were infused with TPN providing 100% of rat's daily caloric intake for 3 consecutive days, followed by 4 more days of normal saline. The carnitine group (n = 7) received the same solution, but which provided 100 mg/kg/day carnitine. Daily food intake was measured and data were analyzed using ANOVA and Student's t-test. Both parenteral solutions depressed food intake maximally by almost 90% by day 3. Carnitine accelerated the normalization of food intake by decreasing the lag period by 1 day. We conclude that the addition of carnitine enhanced the normalization of post-TPN food intake and argue that this may be on the basis of enhanced fatty acid oxidation, a substrate known to play a significant role in the anorexia induced by TPN.
In 1995 a correlation between malnutrition and poor outcome in critically ill patients still exists.
After more than two decades of nutritional awareness, we designed a prospective study to determine whether malnutrition is still a significant issue in hospitalized patients. Patients admitted to an intensive care unit (ICU) were divided into well-nourished and malnourished groups, according to their nutritional status as assessed by serum albumin level and weight/height ratio. Severity of illness, as assessed by the Therapeutic Intervention Scoring System (TISS), was used to further stratify the study population. All patients were followed clinically until discharge or death and their outcome recorded. Of 129 patients studied, 43% were malnourished. Length of hospital stay (p = n.s.), incidence of complications (p < 0.01), and number of patients not discharged from hospital (p < 0.05) were greater in the malnourished patients than in the well-nourished. In patients with less severe degrees of illness, the existence of malnutrition led to a worse outcome than in sicker patients. To further assess the clinical setting in which hospital-related malnutrition develops or is exacerbated, postoperative patients admitted to the ICU (n = 66) were also studied in a nutritional survey; the results of this survey indicate that: (a) the incidence of malnutrition in the surgical population is similar to that in the whole study population, and (b) hospital-related malnutrition in surgical patients mainly develops during their preoperative stay in general wards. Whereas our conclusion that patients' outcome is adversely affected by a poor nutritional status is not new or startling, malnutrition continues to be a persistent problem in hospitalized patients, which can be readily identified using simple and easily available indices and, furthermore, readily treated.
Cancer anorexia: new pathogenic and therapeutic insights.
During tumor growth, anorexia and reduced food intake markedly contribute to the development of malnutrition, thus worsening overall patients' survival. A better understanding of the pathophysiology of eating behavior may lead to new and more effective therapies, aiming at counteracting the detrimental effects of anorexia and reduced food intake on nutritional status and survival in cancer patients. Brain tryptophan and serotonin concentrations seem to play a pivotal role in the regulation of eating behavior. Increased brain serotonin activity is indeed associated with a reduction of food intake. It has been recently hypothesized that increased availability of tryptophan to the brain and the consequent increased serotonin activity may represent the pathogenic mechanism for cancer-associated anorexia. According to this hypothesis, the modulation of brain serotonin activity may result in an improvement of anorexia. Reducing brain tryptophan availability represents a possible mechanism to restore brain serotonin activity to normal. There is evidence that the oral administration of neutral amino acids competing with tryptophan for brain entry results in a significant improvement of cancer anorexia. The same treatment may also be effective in improving secondary anorexia, which is associated with other chronic illnesses, including renal and liver failure, sepsis, and so forth, sharing a similar pathogenic mechanism.
From laboratory to bedside: new strategies in the treatment of malnutrition in cancer patients.
The objective of this review is to present and discuss the current and the possible future perspectives of artificial nutrition in preventing and treating cancer cachexia. English-language studies published in the last 25 years were retrieved using MEDLINE, bibliographies and consultation with experts. MEDLINE search terms included "cancer," "malnutrition," and "nutritional support." In vivo and in vitro controlled studies were selected, and data from each study were independently abstracted by the authors. Data obtained indicate that cancer cachexia is a common manifestation of advanced malignant disease, characterized by marasmus due to impaired nutrient metabolism, weight loss, and anemia. In patients, the presence of cachexia increases morbidity and mortality, delays or impedes the delivery of the adequate treatment, reduces the efficacy of anti-neoplastic therapy, and impairs patient's quality of life. Indirect evidence indicates that cancer cachexia is mediated by circulating cytokines, produced by the host in response to the presence of the malignancy. In the past two decades, nutritional support was used to counteract the detrimental effect of cancer cachexia on the host, but with limited success. More recently, the better understanding of the mechanisms of cancer cachexia and the identification of pharmacologic effects provided by specific nutrients, has formed the rationale for a "new" mode of nutrition therapy/nutritional support, adding pharmacotherapy to adjunctive initial care.
Innervated liver plays an inhibitory role in regulation of food intake.
BACKGROUND: With the onset of eating, the associated rise of dopamine in the lateral hypothalamus (LHA-DA) is thought to regulate quantity of food consumed per meal. Early release of LHA-DA induced by eating is facilitated by oronasal stimulation; we propose that the subsequent LHA-DA response induced by nutrients in the portal vein is dampened by the innervated liver. This was tested by measuring LHA-DA in normal rats: during parenteral feeding to bypass oronasal stimulation, while eating during parenteral feeding, and while eating only. METHODS: Rats had either total liver denervation or sham operation, with placement of a jugular vein catheter and LHA-DA microdialysis cannula. After a 3-week recovery period total liver denervated rats were randomized to parenterally fed, food only, and parenteral plus food groups each with sham-operated controls in which LHA-DA was measured. RESULTS: No difference in LHA-DA release in food only groups occurred between total liver denervated or sham-operated rats. A significantly higher rise in LHA-DA was observed in total liver denervated versus sham-operated rats in parenterally fed (129% +/- 4% versus 116% +/- 2%; p < 0.05) and parenteral plus food (151% +/- 4% versus 134% +/- 4%; p < 0.05) groups. CONCLUSIONS: In total liver denervation versus sham operation, an increase in LHA-DA release occurs during parenteral feeding and eating during parenteral feeding, suggesting that innervated liver inhibits LHA-DA release.
Cracking the riddle of cancer anorexia.
During tumor growth, anorexia and reduced food intake are among the major causes leading to malnutrition and eventually cachexia, which negatively affect patients' outcome. Consistent evidence from our laboratories in rats and humans indicates a key role for ventromedial hypothalamic (VMH) serotonergic system in the development of cancer anorexia. Thus, we postulated that during cancer, increased plasma tryptophan levels (the precursor of serotonin) lead to increased cerebrospinal fluid tryptophan concentrations and increased VMH serotonin synthesis, which then mediates the occurrence of anorexia. However, recent data strongly suggest that factors other than tryptophan supplied to the central nervous system might be involved in the pathogenesis of reduced food intake during tumor growth. Particularly, a significant role appears to be played by interleukin-1 (IL-1). We recently showed that IL-1 infusion in normal rats causes changes in food intake and its determinants, meal number and meal size, similar to those characterizing cancer anorexia, thus supporting the involvement of this cytokine in the development of anorexia. Interestingly, IL-1 and the VMH serotonergic system appear to be closely linked: peripherally infused IL-1 increases brain tryptophan and serotonin concentrations, while intracerebrally infused IL-1 increases neuronal firing rate and serotonin release. We therefore hypothesize that during tumor growth, increased production/secretion of IL-1 occurs, which facilitates the tryptophan supply to the brain. IL-1 can then also act on the VHM itself, where IL-1 receptors exist, to increase its neuronal activity and serotonin release. In other words, we believe that centrally acting IL-1 increases hypothalamic neuronal firing rate and serotonin release, while peripherally acting IL-1 is critical in supplying the hypothalamus with the precursor, tryptophan, in order to maintain the high rate of serotonin synthesis. Also, additional factors recently proposed as mediators of anorexia (including neuropeptide Y and nitric oxide) appear to be part of the hypothesized pathogenic mechanism.
Nutritional issues in cancer management.
The objective of this article was to investigate the relationship between nutrition and cancer, as it relates to the initiation, promotion, and treatment of tumor growth. English-language studies published in the last 25 years were retrieved using MEDLINE, bibliographies, and consultation with experts. MEDLINE search terms included "cancer", "malnutrition," and "nutritional support." In vitro and in vivo controlled studies addressing the impact of nutritional factors on cancer prevention and treatment were selected. Approximately 30% of cancers in the Western countries are diet-related. The presence of malignancy affects patients' nutritional status negatively, leading to increased morbidity and mortality. Standard nutritional support (both enteral and parenteral) is not always effective in significantly improving outcome in malnourished cancer patients, due to characteristic changes in host metabolism. Preliminary studies suggest that newer nutritional-pharmacologic agents may be beneficial in counteracting the derangement of host metabolism, and consequently in ameliorating cancer patients' nutritional status and outcome of malnourishment. This review suggests that dietary manipulations and nutritional-pharmacologic therapy might be highly effective adjuncts in controlling the symptoms of patients with neoplastic disease.
Eating-related increase of dopamine concentration in the LHA with oronasal stimulation.
Previously, we showed that eating was associated with an increase in lateral hypothalamic area dopamine (LHA-DA) release, which returns to previous level when eating stops. We therefore hypothesize that LHA-DA release may be primarily contributed to by oronasal stimulation. To test our hypothesis, microdialysis was used to compare LHA-DA release during oral and intragastric feeding. A gastrostomy tube was inserted in 12 rats. After recovery from surgery, in vivo microdialysis was performed. Six rats were allowed to drink a liquid diet, whereas in another six rats the same liquid diet was infused at paired doses (volume = 4.8 +/- 0.6 ml; time = 5-10 min) through the gastrostomy tube into the stomach. Oral feeding increased baseline LHA-DA from 10.6 +/- 0.2 to 14.0 +/- 0.8 pg/10 microliters dialysate (P < 0.01) within 20 min. No significant change in measured LHA-DA occurred during intragastric feeding [baseline: 10.5 +/- 0.3 pg/10 microliters; postintragastric: 10.2 +/- 0.3 pg/10 microliters (P < 0.01 vs. oral feeding)], indicating that LHA-DA release occurs with oronasal stimulation.
Comparison of long-term feeding pattern between male and female Fischer 344 rats: influence of estrous cycle.
We studied the effect of gender on food intake, meal number, and meal size in eight 10-wk-old female and seven age-matched male Fischer 344 rats for 44 consecutive days. Although food intake (g/100 g body wt) was similar in males and females (5.42 +/- 0.10 vs. 5.13 +/- 0.13 g food.day-1.100 g body wt-1, respectively; not significant), weight gain in males was approximately seven times greater than in female rats (1.49 +/- 0.07 vs. 0.21 +/- 0.03 g/day, respectively; P < 0.001). During this time, males had a relatively constant food intake. They increased their meal size but decreased their meal number. In female rats, food intake was relatively stable for the duration of the study, despite cyclically and reciprocally recurring changes in meal number and meal size, which are synchronized with the estrous cycle. Data confirm that net food intake is a dynamic process and suggest that, in the rat, the homeostasis of food intake in response to external as well as internal stimuli is maintained via the modulation of meal number and size.