Comparison of the performance of four different tools in diagnosing disease-associated anorexia and their relationship with nutritional, functional and clinical outcome measures in hospitalized patients.

BACKGROUND & AIMS: In hospitalized patients, lack of appetite, i.e., disease-associated anorexia, is the main factor determining insufficient food intake and weight loss, which in turn increase morbidity and mortality. Controversies exist on which tool should be preferred when diagnosing anorexia. Aim of the study was to evaluate in hospitalized medical patients, the performance of 4 different tools [i.e., self-assessment of appetite, FAACT-ESPEN score, visual analog scale (VAS), and the Anorexia Questionnaire (AQ)] in assessing disease-associated anorexia and predicting nutritional and clinical variables. MATERIALS AND METHODS: Hospitalized patients consecutively admitted to the Internal Medicine ward at our institution were considered. After informed consent was obtained, patients were asked to self-assess their appetite vs the previous month. The VAS, the FAACT-ESPEN score and the Anorexia Questionnaire were also submitted. Food intake immediately following the interview was recorded. Nutritional (i.e., body weight, height), functional (i.e., handgrip strength) and clinical variables (i.e., length of stay) were registered upon admission and before discharge. RESULTS: We studied 105 patients (74M:31F; 66.2 ± 16.3 yrs). The prevalence of anorexia as assessed by patients' self assessment, FAACT-ESPEN score, and the Anorexia Questionnaire was 23%, 10% and 48%, respectively. VAS did not show any correlation with food intake. Anorexic patients as identified by the self assessment of appetite showed reduced food intake and weaker handgrip strength than non-anorexic. The FAACT-ESPEN score correlated with body weight, food intake and handgrip strength, but was not related with length of stay. Anorexic patients as identified by the Anorexia Questionnaire showed reduced food intake, lower body weight, weaker handgrip strength and longer hospital stay than non-anorexic patients. DISCUSSION: The prevalence of anorexia significantly varies according to the diagnostic tool used. Except for VAS, all the tested tools identify patients with impaired nutritional and functional variables. However, only the Anorexia Questionnaire identifies patients with longer hospital stay. Our results suggest that in clinical practice, modification of appetite reflects different underlying mechanisms whose impacts on clinical outcome measures may differ. Therefore, an ideal anorexia assessment tool does not appear to exist, but it should be chosen according to the outcome measures to be assessed (i.e., Anorexia Questionnaire to predict length of stay).

Caloric restriction and L-carnitine administration improves insulin sensitivity in patients with impaired glucose metabolism.

BACKGROUND: Reduced circulating and tissue carnitine levels, possibly leading to impaired mitochondrial function, have been postulated to be involved in the pathogenesis of insulin resistance. However, whether L-carnitine administration may improve insulin sensitivity in patients with impaired fasting glucose (IFG) or type 2 diabetes mellitus (DM-2) is still controversial. The aim of the study was to explore the role of L-carnitine supplementation in influencing insulin sensitivity. METHODS: A randomized controlled study involving adult outpatients was designed. Adult patients referred to the outpatient clinic and within 10 days of the diagnosis of IFG or DM-2 were consecutively enrolled. Exclusion criteria were concomitant antidiabetic therapy and modifications of lifestyle during the previous 4 weeks. Patients were randomly assigned to receive a hypocaloric diet for 10 days (group C; n = 8) or the same dietetic regimen in addition to oral L-carnitine (2 g twice daily) supplementation (group LC; n = 8). Oral glucose tolerance test (OGTT), fasting plasma insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed at the beginning and end of the study. Data were statistically analyzed using the Student t test for paired and unpaired data. RESULTS: OGTT at 2 hours improved in both groups. Only in the L-carnitine-supplemented group did plasma insulin levels and HOMA-IR significantly decrease when compared to baseline values. CONCLUSIONS: Considering the role of caloric restriction in increasing the intestinal uptake of carnitine, the results suggest that oral L-carnitine administration, when associated with a hypocaloric feeding regimen, improves insulin resistance and may represent an adjunctive treatment for IFG and DM-2.

Tryptophan in wasting diseases: at the crossing between immune function and behaviour.

PURPOSE OF REVIEW: Wasting diseases are characterized by progressive deterioration of nutritional status that negatively influences patients' outcome. The better understanding of the pathogenic mechanisms of wasting may lead to effective therapies. Tryptophan metabolism has unique features suggesting a critical role in influencing human metabolism under normal and pathological conditions. RECENT FINDINGS: During disease, inflammatory response favours the local depletion of the essential amino acid tryptophan, thereby inhibiting cellular proliferation. Tryptophan depletion may also mediate immunotolerance to foreign antigens. In contrast, brain accumulation of tryptophan contributes to wasting by increasing oxidative stress and hypothalamic serotonin neurotransmission, and thereby triggering the onset of sickness behaviour followed by depressive-like behaviour. SUMMARY: Tryptophan metabolism is critical in mediating a number of important biological responses. Restoring tryptophan metabolism may well result in enhanced recovery from disease.

The driving brain: the CNS in the pathogenesis and treatment of anorexia-cachexia syndrome.

Over the past few years, medical care has dramatically improved knowledge of the pathogenic mechanisms of diseases, leading to more effective therapies as well as improved technologies, yielded to enhance survival for diseases that, just a few decades ago, would have been considered lethal. Unfortunately, not all diseases can be completely defeated. In many circumstances, therapies may delay the progression of the disease, leading to improved survival but bringing new issues to light. Of particular interest are nutritional and metabolic alterations due to both prolonged clinical course of disease and long-term therapies. Anorexia-cachexia syndrome often complicates the course of chronic illnesses. Anorexia (i.e., loss of appetite) and cachexia (i.e., loss of weight due to lean body mass and fat-mass wasting) are both associated with a number of diseases. The aim of this article is to highlight the clinical impact of the anorexia-cachexia syndrome and to review current and future etiologic therapeutic approaches.

Free tryptophan/large neutral amino acids ratios in blood plasma do not predict cerebral spinal fluid tryptophan concentrations in interleukin-1-induced anorexia.

Peripheral administration of interleukin-1 (IL-1) reduces food intake and affects brain serotonergic activity, suggesting a causal relationship. Furthermore, IL-1 increases the brain concentrations of the serotonin precursor, tryptophan (TRP), by unclear mechanism(s). We aimed at confirming the link between IL-1 administration, raised brain TRP concentrations and the development of anorexia, and at investigating the mechanisms of TRP entry into the brain. Thirty adult, overnight fasted Sprague-Dawley rats were randomly assigned to i.p. injections of 1 mug/kg BW of IL-1 alpha (n=10) or vehicle (n=10), or to pair-feeding with IL-1 animals (n=10). After 2 h, food intake, blood plasma concentrations of total TRP, free TRP, large neutral amino acids (LNAA; competing with TRP for brain entry) were measured. Cerebral spinal fluid (CSF) TRP concentrations were also measured. TRP brain availability was assessed by calculating the plasma ratio free TRP/LNAA. Following IL-1 injection, food intake significantly declined in IL-1 rats, which was paralleled by decreased plasma free TRP and increased plasma LNAA. Despite a decrease in the free TRP/LNAA ratios in plasma, IL-1 significantly increased concentrations of TRP in CSF. These data show that the acute peripheral administration of IL-1 induces anorexia and raises CSF TRP levels. Considering the possible role of the raised CSF TRP in influencing brain serotonin activity, it is postulated that increased serotonergic neurotransmission could be involved in IL-1 induced anorexia.

Antimyopathic effects of carnitine and nicotine.

PURPOSE OF REVIEW: The clinical course of most chronic diseases is associated with declined energy intake and nutrient-resistant progressive myopathy, characterized by accelerated proteolysis and impaired function. This anorexia/cachexia syndrome leads to deterioration of quality of life, and increased morbidity and mortality. The clinical efficacy of currently available therapeutic strategies is limited and more effective treatments are needed. RECENT FINDINGS: Chronic systemic inflammation, triggered and sustained by cytokines, and increased oxidative stress contribute to the pathogenesis of the anorexia/cachexia syndrome. Carnitine and nicotine have recently been tested as immunomodulating and antioxidant agents. In particular, carnitine supplementation has been shown to reduce chronic inflammation and oxidative stress in hemodialysis patients and, in cancer patients, yielding to reduced fatigue and improved outcome. Nicotine is able to induce the anti-inflammatory activity of the vagus nerve. In animal models of sepsis and cancer, the nicotine-induced supplementation resulted in better protection of nutritional status and improved survival. SUMMARY: In the continuous effort to develop more efficacious strategies against the anorexia/cachexia syndrome, carnitine and nicotine may represent a further therapeutic tool. More clinical studies are needed, however, before their use can be routinely suggested.

Branched-chain amino acids: the best compromise to achieve anabolism?

PURPOSE OF REVIEW: The anorexia-cachexia syndrome is highly prevalent in patients suffering from acute and chronic diseases, including cancer, chronic renal failure and liver cirrhosis. Once it has developed, it significantly influences the clinical course of the underlying disease, simultaneously impinging on patients' quality of life. Unfortunately, currently available therapeutic strategies do not appear to greatly impact on patients' morbidity, mortality and quality of life. More effective therapies are needed to promote appetite and food intake, to preserve lean body mass, and to ameliorate patients' psychological distress. RECENT FINDINGS: Branched-chain amino acids are neutral amino acids with interesting and clinically relevant metabolic effects. Their potential role as antianorexia and anticachexia agents was proposed many years ago, but only recent experimental studies and clinical trials have tested their ability to stimulate food intake and counteract muscle wasting in anorectic, weight-losing patients. By interfering with brain serotonergic activity and by inhibiting the overexpression of critical muscular proteolytic pathways, branched-chain amino acids have been shown to induce beneficial metabolic and clinical effects under different pathological conditions. SUMMARY: Based on the available data, branched-chain amino acids appear to exert significant antianorectic and anticachectic effects, and their supplementation may represent a viable intervention not only for patients suffering from chronic diseases, but also for those individuals at risk of sarcopenia due to age, immobility or prolonged bed rest, including trauma, orthopedic or neurologic patients.

Anorexia and serum leptin levels in hemodialysis patients.

BACKGROUND AND AIMS: Hyperleptinemia is a common feature in hemodialysis (HD) patients. However, the role of increased serum leptin levels in the pathogenesis of HD-related anorexia is still controversial. The purpose of the present prospective study was to ascertain whether hyperleptinemia is causally implicated in the pathogenesis of HD-related anorexia. METHODS: We measured the serum leptin levels and the serum leptin/body mass index (BMI) ratio in 24 healthy subjects and in 49 end-stage renal disease patients on maintenance HD. HD patients were subdivided into anorexic (14/49, 28.5%) and non-anorexic (35/49, 71.5%) according to a questionnaire discriminating for the presence of anorexia-related symptoms. RESULTS: Calorie (kcal/kg/day) and protein (g/ kg/day) intakes were significantly lower in anorexic than in non-anorexic patients (20.1 +/- 1.1 vs. 27.9 +/- 1.3, p = 0.004, and 0.82 +/- 0.05 vs. 1.19 +/- 0.05, p = 0.001, respectively). Accordingly, serum albumin, total lymphocyte count, mid-arm muscle circumference, and the protein equivalence of nitrogen appearance (PNA) were significantly lower in anorexic patients. The serum leptin concentration (ng/ml) was significantly higher in HD patients than in controls, in males (15.33 +/- 3.4 vs. 3.7 +/- 0.3, p = 0.003) and in females (42.3 +/- 7.2 vs. 10.5 +/- 1.3, p = 0.03). Similarly, serum leptin/BMI ratio was significantly higher in HD patients than in controls, in males (0.56 +/- 0.1 vs. 0.16 +/- 0.02, p = 0.0028) and in females (1.8 +/- 0.2 vs. 0.4 +/- 0.04, p < 0.0001). However, serum leptin levels were similar in anorexic and in non-anorexic patients, in males (15.3 +/- 5.6 vs. 16.9 +/- 4.2, p = 0.85) and in females (46.6 +/- 12.9 vs. 47.4 +/- 9.4, p = 0.96). No differences were observed between the 2 groups in the serum leptin/BMI ratio, in males (0.59 +/- 0.2 vs. 0.58 +/- 0.14, p = 0.92) and in females (1.5 +/- 0.4 vs. 1.8 +/- 0.3, p = 0.94). Similarly, no statistically significant differences in terms of serum leptin levels and leptin/BMI ratio were observed between patients with dietary energy intake of <30 or > or =30 kcal/kg/day and between those with a dietary protein intake of <1.2 or > or =1.2 g/kg/day. No significant correlations were found between serum leptin levels and PNA, albumin, cholesterol, total lymphocytes number, weight change, C-reactive protein, fibrinogen, ferritin, and complement. CONCLUSION: The present results indicate that mechanisms other than increases in serum leptin levels might be involved in the pathogenesis of HD-related anorexia.

Tumor-induced changes in host metabolism: a possible role for free tryptophan as a marker of neoplastic disease.

Tumor growth is associated with a number of metabolic abnormalities. Glucose metabolism is deranged as frequently revealed by an impaired oral glucose tolerance test. Lipoprotein lipase activity is depressed, resulting in hypertrigliceridemia after an exogenous lipid load. Also protein metabolism is deranged in cancer patients, as revealed by changes of plasma amino acid profile. Our previous studies on plasma amino acids have shown that increased plasma free tryptophan levels are a frequent finding in cancer patients. To sustain a possible role for free tryptophan as a marker of neoplastic disease, we measured its plasma concentrations in 241 patients with cancer. Plasma free tryptophan concentrations were found to be significantly elevated with respect to healthy controls in patients with breast, lung, colon, stomach, and cancer from various origin. The sensitivity of this marker in predicting the presence of the tumor was highest for stomach and lung cancer patients. High plasma free tryptophan concentrations seem to be directly related to the presence of the tumor, since in breast cancer patients they returned to within normal range after eradicative surgery.