The Appetite loss in older people is an important unmet clinical need in geriatrics. The International Conference on Frailty and Sarcopenia Research (ICFSR) organized a Task Force on April 20th 2022, in Boston, to discuss issues related to appetite loss in older people, in particular, the assessment tools currently available, its evaluation in the primary care setting, and considerations about its management. There is a high heterogeneity in terms of the etiology of appetite loss in older people and a gold standard assessment tool for evaluating this condition is still absent. Although this may render difficult the management of poor appetite in clinical practice, validated assessment tools are currently available to facilitate early identification of appetite loss and support care decisions. As research on biomarkers of appetite loss progresses, assessment tools will soon be used jointly with biomarkers for more accurate diagnosis and prognosis. In addition, efforts to foster the development of drugs with a favorable risk/benefit ratio to combat poor appetite should be strengthened.

Cachexia is a common complication of cancer and is associated with poor quality of life and a decrease in survival. Many patients with cancer cachexia suffer from inflammation associated with elevated cytokines, such as interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF). Single-agent trials to treat cancer cachexia have not led to substantial benefit as the type of cytokine which is elevated has rarely been specified and targeted. Cachexia may also be multifactorial, involving inflammation, anorexia, catabolism, depression, and pain, and targeting the multiple causes will likely be necessary to achieve improvement in weight and appetite. A PUBMED search revealed over 3000 articles on cancer cachexia in the past ten years. We attempted to review any studies related to inflammation and cancer cachexia identified by Google Scholar and PUBMED and further search for articles listed in their references. The National Comprehensive Cancer Network (NCCN) guidelines do not provide any suggestion for managing cancer cachexia except a dietary consult. A more targeted approach to developing therapies for cancer cachexia might lead to more personalized and effective therapy.

The world population is aging and the prevalence of noncommunicable diseases such as diabetes, hypertension, and chronic kidney disease (CKD) will increase significantly. With advances in medical treatment and public health, the human lifespan continues to outpace the health span in such a way that the last decade of life is generally spent in poor health. In 2015, the World Health Organization defined healthy aging as 'the process of developing and maintaining the functional ability that enables wellbeing in older age.' CKD is increasingly being recognized as a model of accelerated aging and is associated with physical performance decline, cognitive decline, falls and fractures, poor quality of life, loss of appetite, and inflammation. Frailty and dementia are the final pathways and key determinants of disability and mortality independent of underlying disease. CKD, dementia, and frailty share a triangular relationship with synergistic actions and have common risk factors wherein CKD accelerates frailty and dementia through mechanisms such as uremic toxicity, metabolic acidosis and derangements, anorexia and malnutrition, dialysis-related hemodynamic instability, and sleep disturbance. Frailty accelerates glomerular filtration decline as well as dialysis induction in CKD and more than doubles the mortality risk. Anorexia is one of the major causes of protein-energy malnutrition, which is also prevalent in the aging population and warrants screening. Healthcare systems across the world need to have a system in place for the prevention of CKD amongst high-risk older adults, focusing on screening for poor prognostic factors amongst patients with CKD such as frailty, poor appetite, and cognitive impairment and providing necessary person-centered interventions to reverse underlying factors that may contribute to poor outcomes.

Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic anorexia attain optimal body mass index (BMI) and nutritional status. However, these may have adverse effects on clinical status. This is an updated version of the original review.

Cancer cachexia is a metabolic disorder syndrome that causes skeletal muscle loss and progressive physical dysfunction, which is observed in more than half of patients with advanced pancreatic cancer. Cancer cachexia is considered to be associated with poor prognosis, worsening adverse events, decreased treatment compliance, and decreased treatment efficacy. The ghrelin receptor agonist leads skeletal muscle gain, weight gain, and the improvement of anorexia in patients with cancer cachexia, and has been approved as an anti-cachexia treatment in Japan. Cancer cachexia patients who present with cachexia symptoms such as appetite loss as well as weight loss are able to receive the treatment of the ghrelin receptor agonist, but the evidence for patients with advanced pancreatic cancer is limited. Further research is needed to evaluate the efficacy of the ghrelin receptor agonist for cancer cachexia in pancreatic cancer patients. Inhibition of inflammatory cytokine such as interleukin-1α and nutrition and exercise therapy are under development for anti-cachexia therapy.

Malnutrition is highly common among cancer patients and is associated with a poor quality of life, increased treatment toxicities and decreased survival. The screening of malnutrition should be performed in an early stage of cancer disease and should be rapid, not expensive and highly sensitive to identify the risk of developing malnutrition. Importantly, international clinical guidelines suggest to perform screening for malnutrition in all cancer patients and if the risk is present, they recommend to perform a full nutritional assessment. During the screening phase, different nutritional parameters are considered including the loss of appetite, low food intake, body weight loss and burden of the disease. These items are present in several screening tools, such as the Nutrition Risk Screening (NRS)-2002, the Malnutrition Universal Screening Tool (MUST) and the Mini Nutritional Assessment (MNA) which represent the most widely used tools to screen for an altered nutritional status in cancer patients. Recently, the Global Leadership Initiative on Malnutrition (GLIM) developed an assessment tool for the diagnosis of malnutrition taking into account the presence of i) involuntary body weight loss, ii) body mass index, iii) low muscle mass, iv) low food intake and disease burden/inflammation; in particular, body weight loss, decreased body mass index (BMI), and low muscle mass are considered as phenotypic criteria, whereas reduced food intake, disease burden and inflammation are defined as etiologic criteria. To perform the diagnosis of malnutrition, GLIM consensus considered the presence of at least one phenotypic and one etiologic criterion. The above-mentioned screening tools were validated in different clinical settings and suggesting the use of one tool vs another is challenging considering, among others, different factors including the type and stage of cancer and the setting (i.e., inpatient or outpatient care). Recent data obtained among large cohorts of cancer patients indicate that personalized nutritional therapy reduced mortality risk and ameliorated quality of life and functionality among cancer patients with high nutritional risk, supporting the urgent need for implementing screening and diagnosis of malnutrition in this context.

Delayed eating rhythms, relative to the sleep/wake period, commonly manifest as a lack of hunger in the morning (morning anorexia) and elevated hunger in the late evening (evening hyperphagia). These intake patterns are associated with adverse mental and physical health outcomes. We aimed to evaluate whether the timing of light exposure, an important environmental signal for circadian synchronization, explains the link between sleep/waketime preferences and delayed diurnal appetite. We also aimed to test whether disruptions in sleep quality, reflecting suboptimal circadian synchronization, identify individuals for whom sleep/waketime preference is associated with delayed diurnal appetite. Participants (N = 150) completed a measure of their sleep/waketime preferences and wore a device to capture their sleep efficiency and naturalistic light exposure for 48 consecutive hours. The timing of light exposure mediated the link between sleep/waketime preferences and evening hyperphagia, but not morning anorexia, such that a later peak in light exposure mitigated some of the risk for evening hyperphagia that was associated with later sleep/waketime preferences. Sleep efficiency moderated the association between sleep/waketime preference and morning anorexia, but not evening hyperphagia. Earlier sleep/waketime preference was associated with less morning anorexia among individuals with high sleep efficiency, but morning anorexia was consistently elevated among individuals with poor sleep efficiency. These results on the relation between sleep/waketime preference and two aspects of delayed diurnal appetite suggest that morning anorexia depends on sleep efficiency and evening hyperphagia may be influenced by the timing of daily light exposure. Future research should assess over longer periods, covering weekdays and weekends, and incorporate momentary reports of meals/snacks and appetite.

We aimed to evaluate the association of circulating growth differentiation factor 15 (GDF-15) with cachexia symptoms and the biological activity of advanced pancreatic cancer (APC). Treatment-naïve patients with liver metastasis of APC or with benign pancreatic disease were retrospectively analyzed. Clinical data, blood samples, and biopsy specimens of liver metastasis were collected prior to anti-cancer treatment. Serum GDF-15 levels and multiple protein expressions in lysates extracted from liver metastasis were measured by enzyme-linked immuno-sorbent assay and reverse-phase protein array, respectively. The cut-off for serum GDF-15 was determined as 3356.6 pg/mL, the mean plus two standard deviations for benign pancreatic disease. The high-GDF-15 group was characterized as showing low Karnofsky performance status (KPS) (p = 0.037), poor Eastern Cooperative Oncology Group performance status (ECOG-PS) (p = 0.049), severe appetite loss (p = 0.011), and high serum levels of carbohydrate antigen 19-9 (p = 0.019) and C-reactive protein (p = 0.009). Tumors of the high-GDF-15 group expressed high levels of phosphorylated (p)JNK (p = 0.007) and pAkt (p = 0.040). APC patients with high serum GDF-15 showed signatures of cachexia and activation of the signaling pathways involving Akt and JNK in the tumor. This study indicated circulating GDF-15 could be associated with cachectic symptoms in APC.

The coronavirus was first identified as the cause of pneumonia in Wuhan, a town in the Hubei Province of China, in December 2019. It usually has respiratory symptoms such as myalgia, headache, cough, and dyspnea. In the medical literature, digestive symptoms and liver disease have been reported in Coronavirus disease in 2019 (COVID-19) patients. In this review article, we summarized the recent studies of gastrointestinal and hepatic manifestations and management of COVID-19. The most common gastrointestinal symptoms were poor appetite/anorexia, nausea/vomiting, diarrhea, and abdominal pain. Elevated aminotransferase has been reported in patients with COVID-19. COVID-19 gastrointestinal and hepatic management is usually symptomatic except for high-risk populations such as patients with inflammatory bowel disease or autoimmune hepatitis, which require special attention.

Cancer cachexia is characterized by weight loss, anorexia, asthenia, and anemia among cancer patients and can lead to their decreased physical function, poor quality of life, and reduced survival. Progestins have been reported to have beneficial effects on appetite improvement in patients with cancer; however, serious complications have been reported as a result of their use. Traditional Chinese medicine (TCM) is a complementary and alternative system of medicine that may be effective in treating cancer cachexia. This review aims to identify existing evidence on the efficacy and safety of traditional Chinese herbs and common TCM technologies in treating cancer cachexia. We searched six databases - the Cochrane Library, PubMed, EMBASE, CINAHL, China National Knowledge Infrastructure, and Wan Fang Database, using medical subject headings and free text. The search was performed in January 2021, and the reference lists of relevant articles were also searched. A total of 4685 citations were identified, and 20 studies were included. The results showed that traditional Chinese herbs can improve appetite, weight, biomarkers, the Karnofsky performance status, cachexia-related symptoms, and quality of life in patients with cancer cachexia. Some traditional Chinese herbs may have superiority in curative effects and safety, compared with progestins. Interestingly, acupuncture can improve appetite, nausea, constipation, and quality of life among patients with cancer cachexia but cannot increase body weight. However, high-quality evidence regarding the effect of TCM technologies in treating cancer cachexia is limited. It would be beneficial to explore the use of moxibustion and other TCM technologies in future studies.

Cancer cachexia is defined as a multifactorial syndrome that causes anorexia and an ongoing loss of skeletal muscle mass (with or without loss of fat mass). When patients got cachexia, the effectiveness and tolerance for anti-cancer therapy is reduced, leading to their poor prognosis. Although known as such disease, there had been no effective cure for cancer cachexia. Ghrelin is a peptide hormone that promotes appetite and improve cachexia. However, there is a limitation as a drug because its half-life is short and must be intravenous injected. Anamorelin is a first novel drug, an orally active, non- peptidic ghrelin mimetic and growth hormone secretagogue approved in Japan in January 2021. Like ghrelin, anamorelin also increases the appetite and lean body mass of patients with cancer cachexia. On the other hand, in clinical trials, there was no statistical significance for increasing the 6-minute walk test distance and recovering non-dominant hand grip strength. As for the functional recovery, a new program has been developed for non-pharmacotherapy with nutritional and exercise interventions. These 2 kinds of interventions will become effective anti-cachexia therapy. Research is also underway to produce anti-cachexia drugs other than anamorelin. Somes are already in their clinical trials. Anti-cachexia therapy will be a new option for treating advanced cancer.

Background: Disease-related anorexia-cachexia is associated with poor prognosis of patients with cardiovascular disease (CVD) or cancer. Growth differentiation factor-15 (GDF-15) has emerged as a central regulator of appetite and body weight. However, the exact role of GDF-15 in lean patients has not been elucidated. Aim: Our aim is to evaluate whether the association of GDF-15 with mortality, including cancer death, differs according to body mass index (BMI) level. Methods and Results: We collected blood samples from 4,061 patients with CV risk factors who were enrolled in the nationwide practice-based J-HOP (Japan Morning Surge-Home Blood Pressure) study. Serum GDF-15 levels were determined by immunoassay analysis. During a mean follow-up period of 6.6 years, we observed 174 (6.7/1000 person-year) all-cause deaths, 68 (2.6/1000 person-year) cancer deaths, and 56 (2.2/1000 person-year) CV deaths. Patients were stratified according to the cut-points of GDF-15 at 1,200 ng/L and BMI at 22.5 and 25.0 kg/m2. The association between the GDF-15/BMI based study groups and each outcome was evaluated by Cox-proportional hazard models with adjustment for established risk factors. The multivariate Cox regression model showed that patients with elevated GDF-15 (≥1,200 ng/L) and low BMI (<22.5 kg/m2) were significantly associated with increased risk of all outcomes [all-cause death, hazard ratio (HR) 3.15, 95% confidence interval (CI) 1.85-5.34, p < 0.001; cancer death, HR 3.52, 95%CI 1.64-7.57, p = 0.001; CV death, HR 2.88, 95%CI 1.20-6.92, p = 0.018, respectively] compared to a reference group with non-elevated GDF-15 and normal BMI (22.5-25.0 kg/m2). In analyses of a subgroup with low BMI (<22.5 kg/m2), patients with elevated GDF-15 had 4.79-fold increased risk of cancer death and 11-fold greater risk of CV death when compared with patients with non-elevated GDF-15 (<1,200 ng/L) after adjustment for established risk factors. Conclusion: In patients with CV risk factors, GDF-15 was associated with all-cause, cancer, and CV death. This relationship was especially remarkable in patients with low BMI. The serum GDF-15 levels in patients with low BMI might be a useful marker to identify the potential for anorexia-cachexia associated with CVD and cancer.

Cancer cachexia often occurs in malignant tumors and is a multifactorial and complex symptom characterized by wasting of skeletal muscle and adipose tissue, resulting in weight loss, poor life quality and shorter survival. The pathogenic mechanism of cancer cachexia is complex, involving a variety of molecular substrates and signal pathways. Advancements in understanding the molecular mechanisms of cancer cachexia have provided a platform for the development of new targeted therapies. Although recent outcomes of early-phase trials have showed that several drugs presented an ideal curative effect, monotherapy cannot be entirely satisfactory in the treatment of cachexia-associated symptoms due to its complex and multifactorial pathogenesis. Therefore, the lack of definitive therapeutic strategies for cancer cachexia emphasizes the need to develop a better understanding of the underlying mechanisms. Increasing evidences show that the progression of cachexia is associated with metabolic alternations, which mainly include excessive energy expenditure, increased proteolysis and mitochondrial dysfunction. In this review, we provided an overview of the key mechanisms of cancer cachexia, with a major focus on muscle atrophy, adipose tissue wasting, anorexia and fatigue and updated the latest progress of pharmacological management of cancer cachexia, thereby further advancing the interventions that can counteract cancer cachexia.

Ageing is associated with reductions in appetite and food intake leading to unintentional weight loss. Such weight loss, particularly through muscle mass reduction, is associated with muscle weakness and functional decline, which represent predictors of poor health outcomes and contribute to frailty in older adults. Exercise-induced anorexia is an established phenomenon in young adults; however appetite and energy intake (EI) responses to resistance exercise are unknown in older adults. Twenty healthy older adults (68 ± 5 years, BMI 26.2 ± 4.5 kg m-2) undertook two 5-h experimental trials. Participants rested for 30 min before being provided with a standardised breakfast (196 kcal, 75.2% carbohydrate, 8.9% protein and 15.9% fat). Participants then rested for 1-h before completing: 1-h resistance exercise bout followed by 2-h of rest (RE) or, a control condition (CON) where participants rested for 3 h, in a randomised crossover design. Appetite perceptions were measured throughout both trials and on cessation, an ad libitum meal was provided to assess EI. A repeated-mesures ANOVA revealed no significant condition x time interaction for subjective appetite (p = 0.153). However, area under the curve for appetite was significantly lower in the RE compared with CON (49 ± 8 mm h-1 vs. 52 ± 9 mm h-1, p = 0.007, d = 0.27). There was no difference in EI (RE = 681 ± 246 kcal; CON = 673 ± 235 kcal; p = 0.865), suggesting that resistance exercise does not affect EI 2 h post-exercise in older adults despite a significant but modest reduction in appetite over a 5-h period. In conclusion, resistance exercise may be an appropriate means for optimising muscle mass adaptations without attenuating acute EI of older adults.

Loss of appetite (anorexia) is a typical behavioral response to infectious diseases that often reduces body weight. Also, anorexia can be observed in cancer and trauma patients, causing poor quality of life and reduced prospects of positive therapeutic outcomes. Although anorexia is an acute symptom, its initiation and endocrine regulation during antiviral immune responses are poorly understood. During viral infections, plasmacytoid dendritic cells (pDCs) produce abundant type I interferon (IFN-I) to initiate first-line defense mechanisms. Here, by targeted ablation of pDCs and various in vitro and in vivo mouse models of viral infection and inflammation, we identified that IFN-I is a significant driver of somatostatin (SST). Consequently, SST suppressed the hunger hormone ghrelin that led to severe metabolic changes, anorexia, and rapid body weight loss. Furthermore, during vaccination with Modified Vaccinia Ankara virus (MVA), the SST-mediated suppression of ghrelin was critical to viral immune response, as ghrelin restrained the production of early cytokines by natural killer (NK) cells and pDCs, and impaired the clonal expansion of CD8+ T cells. Thus, the hormonal modulation of ghrelin through SST and the cytokine IFN-I is fundamental for optimal antiviral immunity, which comes at the expense of calorie intake.

Cannabinoids have been used medicinally for thousands of years. Clinical trials support their use for treatment of chemotherapy-induced nausea and vomiting and HIV- and AIDS-related anorexia. Cancer anorexia cachexia syndrome (CACS) is a common debilitating condition and is associated with poor prognosis. The 2016 European Society for Parenteral and Enteral Nutrition clinical guidelines on nutrition in cancer patients concluded that "there are insufficient consistent clinical data to recommend cannabinoids to improve taste disorders or anorexia in cancer patients." The increased attention that cannabinoids have received in recent years warrants an updated evaluation of the literature on this topic, as practitioners are likely to encounter cancer patients interested in cannabinoid use. A systematic literature search was performed to assess the current body of evidence concerning cannabinoid use for the stimulation of appetite and oral intake by cancer patients. Over the past 20 years, 6 randomized controlled trials have evaluated the impact of cannabinoids on appetite-related outcomes in oncology patients in comparison with a control group or placebo. Based on this literature, cannabinoids do not appear to improve appetite, oral intake, weight, chemosensory function, or appetite-related quality of life. Limitations of the literature include small sample sizes, lack of adjustment for confounding variables, and difficulties conducting true placebo-controlled trials with a drug that may result in psychoactive side effects. Further exploration of the impact of cannabinoid use on CACS by using large, well-designed clinical trials is needed.

Anorexia and cachexia are major clinical problems seen in a large proportion of patients with advanced cancer. Weight loss has also been identified as an indicator of poor prognosis in cancer patients. Around 20% of patients with advanced cancer present mortality from the effects of malnutrition rather than from cancer itself. Early nutrition intervention has seen to improve outcomes in cancer patients such as weight gain, treatment tolerance, and improved quality of life (QoL). Effective therapies for addressing these threatening conditions are lacking. Pharmacotherapeutic agents such as corticosteroids, megestrol acetate, and cyproheptadine have several adverse reactions and also lack satisfactory results. Rasayana therapy is known to prevent loss of body mass and at the same time help to improve appetite and increase patient's QoL. The Rasayana compound used by us to prevent cachexia mainly includes swarna sindoor, Hirak bhasma, and suvarna bhasma. To evaluate benefits of Rasayana therapy on these variables, we maintain complete documentation of different clinical variables in all cancer patients. Here, in this observational study, we analyzed the data collected from a group of stage IV breast cancer patients (n = 30) receiving Rasayana therapy. Patients were followed at an interval of every 15 days from baseline for 3 months. Furthermore, at each visit, there weight was recorded on calibrated digital weight balance. QoL in these patients was recorded at quarterly interval using functional assessment of cancer therapies questionnaire. It was seen that in the duration of 3 months patients appetite increased significantly (P = 0.03). Significant weight gain was seen in patients (P = 0.04). Significant improvement was also seen in QoL especially related to QoL subdomains of physical wellbeing (P = 0.01), emotional wellbeing (P < 0.04), and functional wellbeing (P < 0.001). Rasayana therapy was seen to be well tolerated by all patients.

Malnutrition is highly prevalent in liver cirrhosis and its presence carries important prognostic implications. The clinical conditions and pathophysiological mechanisms that cause malnutrition in cirrhosis are multiple and interrelated. Anorexia and liver decompensation symptoms lead to poor dietary intake; metabolic changes characterised by elevated energy expenditure, reduced glycogen storage, an accelerated starvation response and protein catabolism result in muscle and fat wasting; and, malabsorption renders the cirrhotic patient unable to fully absorb or utilise food that has been consumed. Malnutrition is therefore a considerable challenge to manage effectively, particularly as liver disease progresses. A high energy, high protein diet is recognised as standard of care, yet patients struggle to follow this recommendation and there is limited evidence to guide malnutrition interventions in cirrhosis and liver transplantation. In this review, we seek to detail the factors which contribute to poor nutritional status in liver disease, and highlight complexities far greater than "poor appetite" or "reduced oral intake" leading to malnutrition. We also discuss management strategies to optimise nutritional status in this patient group, which target the inter-related mechanisms unique to advanced liver disease. Finally, future research requirements are suggested, to develop effective treatments for one of the most common and debilitating complications afflicting cirrhotic patients.

Prognostic prediction has been reported to affect the decision of doctors and non-physician health care providers such as nurses, social workers, pastors, and hospice volunteers on the selection of appropriate medical interventions. This was a case of a 65-year-old woman who presented with a poor oral intake. The patient had a history of sigmoid colon cancer with abdominal wall metastasis and peritoneal dissemination. On the day of admission, nausea, anorexia, and malaise were noted, requiring immediate intervention. The patient's prognosis was predicted using the Palliative Prognostic Index. The pharmacist suggested the use of dexamethasone tablets in order to alleviate the patient's symptoms. Indeed, the administration of dexamethasone alleviated the symptoms of nausea, loss of appetite, and malaise. To the best of our knowledge, this is the first case report to demonstrate that prognosis prediction is important not only for other medical staff but also for pharmacists when deciding the need to initiate a treatment and continue such treatment, and when providing pharmacist interventions.

Exclusion of nausea (N) and vomiting (V) from detailed consideration as symptoms of COVID-19 is surprising as N can be an early presenting symptom. We examined the incidence of NV during infection before defining potential mechanisms. We estimate that the overall incidence of nausea (median 10.5%), although variable, is comparable with diarrhea. Poor definition of N, confusion with appetite loss, and reporting of N and/or V as a single entity may contribute to reporting variability and likely underestimation. We propose that emetic mechanisms are activated by mediators released from the intestinal epithelium by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) modulate vagal afferents projecting to the brainstem and after entry into the blood, activate the area postrema (AP) also implicated in anorexia. The receptor for spike protein of SARS-CoV-2, angiotensin 2 converting enzyme (ACE2), and transmembrane protease serine (for viral entry) is expressed in upper gastrointestinal (GI) enterocytes, ACE2 is expressed on enteroendocrine cells (EECs), and SARS-CoV-2 infects enterocytes but not EECs (studies needed with native EECs). The resultant virus-induced release of epithelial mediators due to exocytosis, inflammation, and apoptosis provides the peripheral and central emetic drives. Additionally, data from SARS-CoV-2 show an increase in plasma angiotensin II (consequent on SARS-CoV-2/ACE2 interaction), a centrally (AP) acting emetic, providing a further potential mechanism in COVID-19. Viral invasion of the dorsal brainstem is also a possibility but more likely in delayed onset symptoms. Overall, greater attention must be given to nausea as an early symptom of COVID-19 and for the insights provided into the GI effects of SARS-CoV-2.