Leucine-Rich Diet Improved Muscle Function in Cachectic Walker 256 Tumour-Bearing Wistar Rats.

Skeletal muscle atrophy occurs in several pathological conditions, such as cancer, especially during cancer-induced cachexia. This condition is associated with increased morbidity and poor treatment response, decreased quality of life, and increased mortality in cancer patients. A leucine-rich diet could be used as a coadjutant therapy to prevent muscle atrophy in patients suffering from cancer cachexia. Besides muscle atrophy, muscle function loss is even more important to patient quality of life. Therefore, this study aimed to investigate the potential beneficial effects of leucine supplementation on whole-body functional/movement properties, as well as some markers of muscle breakdown and inflammatory status. Adult Wistar rats were randomly distributed into four experimental groups. Two groups were fed with a control diet (18% protein): Control (C) and Walker 256 tumour-bearing (W), and two other groups were fed with a leucine-rich diet (18% protein + 3% leucine): Leucine Control (L) and Leucine Walker 256 tumour-bearing (LW). A functional analysis (walking, behaviour, and strength tests) was performed before and after tumour inoculation. Cachexia parameters such as body weight loss, muscle and fat mass, pro-inflammatory cytokine profile, and molecular and morphological aspects of skeletal muscle were also determined. As expected, Walker 256 tumour growth led to muscle function decline, cachexia manifestation symptoms, muscle fibre cross-section area reduction, and classical muscle protein degradation pathway activation, with upregulation of FoxO1, MuRF-1, and 20S proteins. On the other hand, despite having no effect on the walking test, inflammation status or muscle oxidative capacity, the leucine-rich diet improved muscle strength and behaviour performance, maintained body weight, fat and muscle mass and decreased some protein degradation markers in Walker 256 tumour-bearing rats. Indeed, a leucine-rich diet alone could not completely revert cachexia but could potentially diminish muscle protein degradation, leading to better muscle functional performance in cancer cachexia.

Redox regulation by carotenoids: Evidence and conflicts for their application in cancer.

Carotenoids have been constantly investigated since the early fifty for their chemical, biochemical and biological properties being presence in foods. Among the more than 1100 carotenoids synthesized by plants and microorganisms, approximately 50 are present in the human diet, and about 20 can be detected in human blood and tissues. Review articles that discuss the anticancer and cancer preventing activity of phytochemicals have often in common the difficulty to find a coherency between the results deriving from experimental studies and the controversial or weak clinical indications arising from epidemiological and interventional studies. In this scenario, the class of carotenoids does not represent an exception. In fact, according with World Cancer Research Fund, strong evidence exists that high-dose supplementation of ß-carotene increases the risk of lung cancer, while for other types of cancer, the protective or harmful effects of food-containing carotenoids or carotenoid supplements have been considered limited, suggestive or unlikely. The analysis of the mechanistic evidence is complicated by the double nature of carotenoids being molecules acting either as antioxidant or pro-oxidant compounds. The present review analyzes the ambiguity and the unexpected results deriving from the epidemiological and interventional studies and discusses how the effects of carotenoids on cancer risk can be explained by understanding their capacity to modulate the cellular antioxidant response, depending on the concentration applied and the cellular metabolism. In the final part, a new global approach is proposed to study the contribution of carotenoids, but also of other phytochemicals, to disease prevention, including cancer.

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies.

As a multifactorial disease, treatment of cancer depends on understanding unique mechanisms involved in its progression. The cancer stem cells (CSCs) are responsible for tumor stemness and by enhancing colony formation, proliferation as well as metastasis, and these cells can also mediate resistance to therapy. Furthermore, the presence of CSCs leads to cancer recurrence and therefore their complete eradication can have immense therapeutic benefits. The present review focuses on targeting CSCs by natural products in cancer therapy. The growth and colony formation capacities of CSCs have been reported can be attenuated by the dietary agents. These compounds can induce apoptosis in CSCs and reduce tumor migration and invasion via EMT inhibition. A variety of molecular pathways including STAT3, Wnt/ß-catenin, Sonic Hedgehog, Gli1 and NF-κB undergo down-regulation by dietary agents in suppressing CSC features. Upon exposure to natural agents, a significant decrease occurs in levels of CSC markers including CD44, CD133, ALDH1, Oct4 and Nanog to impair cancer stemness. Furthermore, CSC suppression by dietary agents can enhance sensitivity of tumors to chemotherapy and radiotherapy. In addition to in vitro studies, as well as experiments on the different preclinical models have shown capacity of natural products in suppressing cancer stemness. Furthermore, use of nanostructures for improving therapeutic impact of dietary agents is recommended to rapidly translate preclinical findings for clinical use.

Nutraceuticals and their role in tumor angiogenesis.

Angiogenesis plays a pivotal role in cancer initiation, maintenance, and progression. Diet may inhibit, retard or reverse these processes affecting angiogenesis (angioprevention). Nutraceuticals, such as omega-3 fatty acids, amino acids, proteins, vitamins, minerals, fibers, and phenolic compounds, improve health benefits as they are a source of bioactive compounds that, among other effects, can regulate angiogenesis. The literature concerning the pro-angiogenic and/or anti-angiogenic nutraceuticals and the possible activated pathways in cancer and other non-neoplastic diseases by in vivo and in vitro experiments are reviewed.

[Real-world study in oncological outpatients of an oral supplement enriched with ω-3 fatty acids - effect on quality of life and nutritional parameters]. / Estudio en vida real de un suplemento oral enriquecido con ácidos grasos ω-3 en pacientes ambulatorios oncológicos: efecto sobre la calidad de vida y los parámetros nutricionales.

INTRODUCTION: Background: cancer patients are a group at high nutritional risk. Oral nutritional supplementation (ONS) can improve nutritional status. Objective: the objective of our study was to evaluate the effectiveness on nutritional parameters and quality of life of a ω3-enriched ONS in oncology outpatients in a real-world study. Material and methods: a total of 35 outpatient cancer patients who received 2 ONS per day were recruited. Chemistry, anthropometric, impedance measurement, nutritional survey, malnutrition universal screening tool (MUST) test, and EQ5D quality of life test were all used before and after 3 months of intervention. Results: mean age was 65.4 ± 10.7 years (18 females/17 males). Mean completion of the group was 81.7 ± 7.2 %. During the intervention, total protein (1.5 ± 0.2 g/dL; p = 0.01), albumin (0.9 ± 0.1 mg/dL; p = 0.04), and transferrin (53.9 ± 21.1 mg/dL; p = 0.02) levels increased. At the beginning of the study, 100 % of the patients were in the high nutritional risk category according to MUST. After the intervention, 34.3 % (n = 12) were in the low nutritional risk category, 51.4 % (n = 18) in the moderate nutritional risk category, and only 14.3 % (n = 5) in the category of high nutritional risk; previously, 100 % of patients had high nutritional risk (p = 0.02). The total score in the quality of life test increased significantly (0.51 ± 0.06 vs 0.84 ± 0.03 points; p = 0.01), with improvement in 5 dimensions. Conclusions: the use of a ω3-enriched ONS in a real-world study with cancer outpatients showed a beneficial effect on nutritional parameters and quality of life.

INTRODUCCIÓN: Antecedentes: los pacientes oncológicos son un grupo de alto riesgo nutricional. Los suplementos orales nutricionales (SON) pueden ayudar a mejorar su situación nutricional. Objetivo: el objetivo de nuestro estudio fue evaluar en un estudio en vida real la efectividad sobre los parámetros nutricionales y la calidad de vida de un SON enriquecido con ω-3 en pacientes ambulatorios oncológicos. Material y métodos: se reclutaron 35 pacientes oncológicos ambulatorios que recibieron 2 SON al día. Se realizaron: valoración bioquímica y antropométrica, impedanciometría, encuesta nutricional, test Malnutrition Universal Screening Tool (MUST) y test de calidad de vida EQ5D, antes y a los 3 meses de intervención. Resultados: la edad media fue de 65,4 ± 10,7 años (18 mujeres/17 hombres). La cumplimentación media del grupo fue de un 81,7 ± 7,2 %. Durante la intervención aumentaron los niveles de proteínas totales (1,5 ± 0,2 g/dl; p = 0,01), albúmina (0,9 ± 0,1 mg/dl; p = 0,04) y transferrina (53,9 ± 21,1 mg/dl; p = 0,02). Al inicio del estudio, un 100 % de los pacientes presentaban en el test MUST la categoría de alto riesgo nutricional. Tras la intervención, un 34,3 % (n = 12) presentaban la categoría de bajo riesgo nutricional, un 51,4 % (n = 18) presentaban en el test MUST la categoría de moderado riesgo nutricional, y solo un 14,3 % (n = 5) presentaban la categoría de alto riesgo nutricional; previamente, el 100 % de los pacientes tenían la categoría alto riesgo (p = 0,02). La puntuación total del test de calidad de vida aumentó significativamente (0,51 ± 0,06 vs. 0,84 ± 0,03 puntos; p = 0,01), mejorando cualitativamente las 5 dimensiones. Conclusiones: la utilización de un SON enriquecido con ω-3 en pacientes oncológicos ambulatorios en condiciones de vida real muestra un efecto beneficioso sobre los parámetros nutricionales y la calidad de vida.

Vitamin D supplementation prior to or during COVID-19 associated with better 3-month survival in geriatric patients: Extension phase of the GERIA-COVID study.

BACKGROUND: The objective of this extension phase of the quasi-experimental GERIA-COVID study was to determine whether vitamin D3 supplementation taken prior to or during COVID-19 was associated with better 3-month survival in geriatric patients hospitalized for COVID-19. METHODS: Intervention group was defined as all participants supplemented with vitamin D3 prior to or during COVID-19 (n = 67). Supplements were either bolus vitamin D3 (ie, 50,000 IU per month, or 80,000 IU or 100,000 IU or 200,000 IU every 2-3 months), or daily supplementation with 800 IU. Comparator group involved those without vitamin D supplements (n = 28). Outcome was 3-month mortality. Covariables were age, sex, functional abilities, history of malignancies, cardiomyopathy, undernutrition, number of acute health issues, antibiotics use, systemic corticosteroids use, and 25(OH)D concentration. RESULTS: 76.1 % (n = 51) of participants survived at 3 months in Intervention group, compared to only 53.6 % (n = 15) in Comparator group (P = 0.03). The fully-adjusted hazard ratio for 3-month mortality was HR = 0.23 [95 %CI: 0.09;0.58](P = 0.002) in Intervention group compared to Comparator group. Intervention group had also longer survival time (log-rank P = 0.008). CONCLUSIONS: Vitamin D3 supplementation was associated with better 3-month survival in older COVID-19 patients.

Inhibitory Potential of Dietary Nutraceuticals on Cellular PI3K/Akt Signaling: Implications in Cancer Prevention and Therapy.

BACKGROUND: The phosphatidyl inositol-3 kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) signaling has been associated with many cellular physiological events, such as proliferation, maturation, survival, and metabolism. Besides its role in normal cells, the pathway is often upregulated in various cancers. Due to its prominent role in the cancer progression events, it is now being considered as a target for cancer therapy and cancer chemoprevention. OBJECTIVES: The present review provides a concise outline of the role of the PI3K/Akt/mTOR pathway in carcinogenesis and progression events, including metastasis, drug resistance and stemness. Further, emphasis needs to be placed on the PI3K/Akt/mTOR pathway inhibitory potentials of various food-derived bioactive components in cancer prevention. METHODS: Data on the PI3K/Akt/mTOR inhibiting natural products and their bioactive compounds have been obtained from PubMed/Medline, Scopus, Eurekaselect, etc. Findings from the above citation databases from 2000-2021 are included in the manuscript. RESULTS: Numerous compounds from plants have been isolated and identified as anticancer agents; among these, a predominant class is nutraceuticals. The PI3K pathway is the predominant target of these natural products, and many of these drug candidates are under various stages of drug development. These compounds have shown a significant inhibitory effect on the kinase activities of PI3K and Akt, resulting in the abrogation of cancer initiation and progression events. In addition, these compounds have been shown to reverse the resistance to chemotherapeutic drugs and also reduce the population of cancer stem cells. CONCLUSION: The nutraceuticals are promising candidates as anticancer agents by blocking PI3K signaling cascades. As the PI3K is a central pathway to various receptors signaling, the dietary intervention may prove to be highly effective.

Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities.

Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet program. The ketogenic diet (KD) has recently emerged as a metabolic therapy in cancer treatment, targeting cancer cell metabolism rather than a conventional dietary approach. The ketogenic diet (KD), a high-fat and very-low-carbohydrate with adequate amounts of protein, has shown antitumor effects by reducing energy supplies to cells. This low energy supply inhibits tumor growth, explaining the ketogenic diet's therapeutic mechanisms in cancer treatment. This review highlights the crucial mechanisms that explain the ketogenic diet's potential antitumor effects, which probably produces an unfavorable metabolic environment for cancer cells and can be used as a promising adjuvant in cancer therapy. Studies discussed in this review provide a solid background for researchers and physicians to design new combination therapies based on KD and conventional therapies.

Postbiotics, Metabolic Signaling, and Cancer.

Postbiotics are health-promoting microbial metabolites delivered as a functional food or a food supplement. They either directly influence signaling pathways of the body or indirectly manipulate metabolism and the composition of intestinal microflora. Cancer is the second leading cause of death worldwide and even though the prognosis of patients is improving, it is still poor in the substantial part of the cases. The preventable nature of cancer and the importance of a complex multi-level approach in anticancer therapy motivate the search for novel avenues of establishing the anticancer environment in the human body. This review summarizes the principal findings demonstrating the usefulness of both natural and synthetic sources of postbotics in the prevention and therapy of cancer. Specifically, the effects of crude cell-free supernatants, the short-chain fatty acid butyrate, lactic acid, hydrogen sulfide, and ß-glucans are described. Contradictory roles of postbiotics in healthy and tumor tissues are highlighted. In conclusion, the application of postbiotics is an efficient complementary strategy to combat cancer.

[Analysis of nutritional interventions in the care process of oncological patients in Andalusia - The NOA project]. / Análisis de las intervenciones nutricionales en el proceso asistencial del paciente oncológico en Andalucía: el proyecto NOA.

INTRODUCTION: Introduction: malnutrition in cancer patients can lead to a reduction in patient quality of life, increased morbidity and mortality, and associated healthcare costs. Objective: to analyze nutritional interventions in the different phases of the oncological process, integrating the needs of patients and those of healthcare professionals. Material and methods: "Design Thinking" techniques were used to address the analysis of the current situation and identify key aspects. Thirteen professionals from 8 public health centers (endocrinology and nutrition, medical and radiotherapy oncology, primary care (PC), nursing and dietetics) participated in the study. Results: nutritional screening is not carried out in a systematic way in the different phases of the oncological process, and there is no universal consensus on the protocols for action and nutritional intervention. A wide compliance with the pathways and referral times of the selected processes has been observed. In the therapeutic phase, there is the possibility of consulting the Clinical Nutrition and Dietetics Unit (UNCYD) and 75 % have specific referral protocols. The nurse case manager is present in all hospitals and in PC. Patient access to the center psychologist was possible in 87 % of the hospitals. Participation of the UNCYD in Tumor Committees was low (only in 25 % of the centers). In all centers there is some kind of collaboration and support by patient associations and the School of Patients, especially in the therapeutic and the control and follow-up phases. Conclusions: variations are observed between the different hospitals and areas in Andalusia, both in terms of means and structures and in activities and procedures. Key points have been selected and prioritized to improve nutritional care in oncology.

INTRODUCCIÓN: Introducción: la desnutrición en los pacientes oncológicos puede conllevar una reducción de la calidad de vida del paciente y un aumento de la morbimortalidad y de los costes sanitarios asociados. Objetivos: analizar las intervenciones nutricionales en las diferentes fases del proceso oncológico, integrando las necesidades de los pacientes y las de los profesionales sanitarios. Material y métodos: se utilizaron técnicas de Design Thinking para abordar el análisis de la situación actual e identificar los aspectos clave. Participaron 13 profesionales de 8 centros sanitarios (endocrinología y nutrición, oncología médica y radioterápica, atención primaria (AP), enfermería y dietética) públicos de Andalucía. Resultados: no se realiza cribado nutricional de forma sistemática en las diferentes fases del proceso oncológico, y no existe consenso universal en los protocolos de actuación e intervención nutricional. Existe un cumplimiento generalizado de los circuitos y tiempos de derivación de los procesos seleccionados. En la fase terapéutica se dispone de la posibilidad de consultar a la Unidad de Nutrición Clínica y Dietética (UNCYD) y el 75 % disponen de protocolos específicos de derivación. La enfermera gestora de casos está presente en todos los hospitales y en AP. El acceso del paciente al psicólogo del centro era posible en el 87 % de los hospitales. Escasa participación de la UNCYD en los Comités de Tumores (solo en el 25 % de los centros). En todos los centros existe algún tipo de colaboración y apoyo de las asociaciones de pacientes y de la Escuela de Pacientes, especialmente en las fases terapéuticas y de control y seguimiento. Conclusiones: se observan variaciones entre los diferentes hospitales y territorios de Andalucía, tanto en la disposición de medios y estructuras como en las actividades y procedimientos. Se han seleccionado y priorizado puntos clave para mejorar la atención nutricional en oncología.

Clinical practice guidelines for the nutritional risk screening and assessment of cancer patients: a systematic quality appraisal using the AGREE II instrument.

PURPOSE: To evaluate the quality of published clinical practice guidelines (CPGs) regarding the nutritional risk screening and assessment of cancer patients and to identify high-quality CPGs for clinical healthcare professionals. METHODS: Guidelines for the nutritional risk screening and assessment of cancer patients were comprehensively searched in eight electronic databases, including The Lancet, PubMed, Cochrane Library, Excerpta Medica dataBASE (EMBASE), Web of Science, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBMdisc), and Wan Fang Data, through August 2020. Six relevant guideline databases, including the National Comprehensive Cancer Network (NCCN), the National Guideline Clearinghouse (NGC), the Guideline International Network (GIN), the New Zealand Guidelines Group (NZGG), the China Guideline Clearinghouse (CGC), and Medlive, and relevant nutrition society websites, were also searched through August 2020. The methodological quality of the included CPGs was appraised independently by three assessors using the Appraisal of Guidelines for Research and Evaluation, 2nd edition (AGREE II) tool. RESULTS: Seven CPGs were located, and the domain with the highest percentage was "clarity of presentation" (85.44%), while the domain with the lowest percentage was "applicability" (40.26%). From the AGREE II results, two guidelines were rated as "strongly recommended," three were assessed as "recommended with modifications," and two were deemed as "not recommended." CONCLUSION: Considering that the two "strongly recommended" guidelines were developed within the American and European contexts, translation, validation, and cultural adaptation are recommended prior to implementing these guidelines in other countries or healthcare contexts to improve their effectiveness and sensitivity for local cancer patients. TRIAL REGISTRATION: PROSPERO registration of the study protocol: CRD42020177390 (July 5, 2020).

Dietary Supplement Use after Cancer Diagnosis in Relation to Total Mortality, Cancer Mortality and Recurrence: A Systematic Review and Meta-Analysis.

To study post-diagnosis dietary supplement use in relation to total mortality, cancer mortality and recurrence among cancer survivors. PubMed and Cochrane Library were searched until April 2019 for observational studies (OS) and randomized clinical trials (RCT). Pooled risk ratios (RR) were calculated using random-effects models. Compared to no supplementation, calcium supplementation was associated with lower total (RR = 0.88, 95% confidence interval (CI): 0.77-1.00, I2=0%, four OS) and cancer mortality (RR = 0.71, 95% CI: 0.53-0.95, I2=0%, three OS) among all cancer survivors, and cancer mortality among colorectal cancer survivors (RR = 0.66, 95% CI: 0.47-0.94, I2=0%, two OS). Vitamin D supplementation was associated with lower total mortality (RR = 0.86, 95% CI: 0.76-0.99, I2=0%, three OS and two RCT). Among breast cancer survivors, supplementation with vitamin C (RR = 0.79, 95% CI: 0.68-0.92, I2=0%, four OS), D (RR = 0.85, 95% CI: 0.72-0.99, I2=0%, two OS), and E (RR = 0.76, 95% CI: 0.64-0.90, I2=0%, three OS) was associated with lower total mortality, while multivitamins (RR = 0.79, 95% CI: 0.64-0.97, I2=0%, two OS), vitamin C (RR = 0.76, 95% CI: 0.64-0.91, I2=0%, two OS), and E (RR = 0.69, 95% CI: 0.55-0.85, I2=0%, two OS) with lower cancer recurrence. Conclusions: Findings are mostly based on OS. More RCTs are needed to justify any recommendation for use.

Vitamin C and Cell Death.

Significance: Persistent oxidative stress is a common feature of cancer cells, giving a specific weapon to selectively eliminate them. Ascorbate in pharmacological concentration can contribute to the suspended formation of hydroxyl radical via the Fenton reaction; thus, it can be an important element of the oxidative stress therapy against cancer cells. Recent Advances: The main components of ascorbate-induced cell death are DNA double-strand breaks via the production of hydroxyl radical and ATP depletion due to the activation of poly (ADP-ribose) polymerase 1. Presumably, DNA damage can be the primary contributor to the anticancer activity of pharmacological ascorbate, as opposed to the rupture of bioenergetics. The caspase independency of high-dose ascorbate-induced cell death proposed the possible involvement of several types of cell death, such as ferroptosis, necroptosis, and autophagy. Critical Issues: Ascorbate can target at least two key molecular features of cancer cells as a part of the anticancer therapy: the intrinsic or acquired resistance to cell death and the dysregulated metabolism of cancer cells. It seems probable that different concentrations of ascorbate alter the nature of induced cell death. Autophagy and necroptosis may play a role at intermediate concentrations, but caspase-independent apoptosis may dominate at higher concentrations. However, ascorbate behaves as an effective inhibitor of ferroptosis that may have crucial importance in its possible clinical application. Future Directions: The elucidation of the details and the links between high-dose ascorbate-induced cancer selective cell death mechanisms may give us a tool to form and apply synergistic cancer therapies. Antioxid. Redox Signal. 34, 831-844.

[Ketogenic diet: a new nutritional strategy for cancer therapy?] / Le régime cétogène : une stratégie alimentaire efficace en complément des traitements contre le cancer ?

Cancer is a disease that can appear in several tissues and that kills more than 150 000 people in France every year. Cancer cells have mutations in their genome that lead to changes in their metabolism, compared to healthy cells. They use mostly glycolysis as their energy source, but not fatty acid oxidation. Currently, treatments used against cancer are nonspecific and have many side effects. Thus it appears increasingly important to find new strategies against cancer cells progression while protecting surrounding healthy cells and decreasing side effects. Ketogenic diet, which is a low-sugar high-fat diet, could be an interesting candidate as it alters the energy machinery of the cell and keeps away its primary energy source (glucose). This diet is largely used to treat refractory epilepsy and begins to be studied in oncology as well. This article describes the scientific evidence of the beneficial effects of the ketogenic diet and aims at showing how this complementary treatment could be useful against several cancers.

TITLE: Le régime cétogène : une stratégie alimentaire efficace en complément des traitements contre le cancer ? ABSTRACT: Le cancer est une pathologie qui touche tout type de tissu et qui tue chaque année en France plus de 150 000 personnes. Les cellules cancéreuses présentent des modifications dans leur métabolisme par rapport aux cellules saines, puisqu'elles tirent leur énergie très majoritairement de la glycolyse anaérobie et non de la phosphorylation oxydative mitochondriale : on parle de l'effet Warburg. À l'heure actuelle, les traitements les plus utilisés pour soigner le cancer en routine sont des traitements dits non spécifiques qui présentent de nombreux effets secondaires, altérant la vie des patients. Il semble de plus en plus crucial de trouver de nouvelles stratégies pour lutter contre la progression des cellules cancéreuses. Le régime cétogène, pauvre en sucres et riche en lipides, est un candidat intéressant, puisqu'il affaiblit la machinerie énergétique de la cellule cancéreuse. Ce régime est déjà utilisé dans le cadre de la prise en charge de l'épilepsie réfractaire aux traitements classiques, et commence à être étudié en cancérologie également. Cet article, qui fait le point sur les preuves scientifiques des effets bénéfiques du régime cétogène, souligne son intérêt thérapeutique potentiel comme traitement complémentaire pour lutter contre certains cancers.

Effects of 4 weeks of Lactobacillus plantarum 299v supplementation on nutritional status, enteral nutrition tolerance, and quality of life in cancer patients receiving home enteral nutrition - a double-blind, randomized, and placebo-controlled trial.

OBJECTIVE: Several human trials have confirmed that Lactobacillus plantarum 299v (Lp299v) relief the gastrointestinal symptoms observed in patients with irritable bowel syndrome, such as nausea, vomiting, and diarrhea. These symptoms are similar to those associated with home enteral nutrition and they affect nutritional status as well as patients' quality of life. The aims of this study were to determine the effect of Lp299v on nutritional status, enteral formula tolerance, and quality of life in cancer patients. PATIENTS AND METHODS: The current double-blind, randomized, and placebo-controlled study included 35 cancer patients receiving home enteral nutrition. There were 2 groups of participants consuming either 2 x 10^10 CFU of Lp299v (n=21) or placebo (n=14) for 4 weeks. RESULTS: An increase in the serum albumin concentration was significantly higher in the Lp299v group than in the placebo group at the endpoint (p=0.032). Moreover, the changes in the frequency of vomiting and flatulence were significantly reduced at week 4 compared to baseline in the Lp299v group (p=0.0117). The improvement of quality of life was observed in both groups; however, with no statistically significant differences between the analyzed groups (p>0.05). CONCLUSIONS: We have demonstrated that administration of Lp299v in cancer patients receiving home enteral nutrition may improve laboratory parameters, predominantly the concentration of albumin, however, overall it does not have an impact on nutritional status. Lp299v may reduce the gastrointestinal symptoms related to enteral nutrition; notwithstanding, the improvement of quality of life may be the result of enteral nutrition rather than the effect of administration of Lp299v.

Gut/Oral Bacteria Variability May Explain the High Efficacy of Green Tea in Rodent Tumor Inhibition and Its Absence in Humans.

Consumption of green tea (GT) and GT polyphenols has prevented a range of cancers in rodents but has had mixed results in humans. Human subjects who drank GT for weeks showed changes in oral microbiome. However, GT-induced changes in RNA in oral epithelium were subject-specific, suggesting GT-induced changes of the oral epithelium occurred but differed across individuals. In contrast, studies in rodents consuming GT polyphenols revealed obvious changes in epithelial gene expression. GT polyphenols are poorly absorbed by digestive tract epithelium. Their metabolism by gut/oral microbial enzymes occurs and can alter absorption and function of these molecules and thus their bioactivity. This might explain the overall lack of consistency in oral epithelium RNA expression changes seen in human subjects who consumed GT. Each human has different gut/oral microbiomes, so they may have different levels of polyphenol-metabolizing bacteria. We speculate the similar gut/oral microbiomes in, for example, mice housed together are responsible for the minimal variance observed in tissue GT responses within a study. The consistency of the tissue response to GT within a rodent study eases the selection of a dose level that affects tumor rates. This leads to the theory that determination of optimal GT doses in a human requires knowledge about the gut/oral microbiome in that human.

The legitimacy and safety of using alternative diets in cancer.

Alternative diets are used by cancer patients, especially among those who are not treated with conventional methods. Due to worrying data published by the World Health Organisation and its Agenda, the International Agency for Research on Cancer and the International Cancer Union, as well as epidemiological data from all over the world, it has been concluded that cancer will be the main cause of death in the world and that, therefore, the popularity of alternative diets among cancer patients may increase. The paper reviews the scientific literature and assesses the legitimacy and safety of selected alternative diets, as well as the description of research in terms of assumed anticancer efficacy in the following diets: ketogenic, Dr. Budwig and macrobiotic. The article also contains a summary of the analyzed scientific research and conclusions concerning the legitimacy of their use by cancer patients.

Nutritional Therapy to Modulate Tryptophan Metabolism and Aryl Hydrocarbon-Receptor Signaling Activation in Human Diseases.

The aryl hydrocarbon receptor (AhR) is a nuclear protein which, upon association with certain endogenous and exogenous ligands, translocates into the nucleus, binds DNA and regulates gene expression. Tryptophan (Trp) metabolites are one of the most important endogenous AhR ligands. The intestinal microbiota is a critical player in human intestinal homeostasis. Many of its effects are mediated by an assembly of metabolites, including Trp metabolites. In the intestine, Trp is metabolized by three main routes, leading to kynurenine, serotonin, and indole derivative synthesis under the direct or indirect involvement of the microbiota. Disturbance in Trp metabolism and/or AhR activation is strongly associated with multiple gastrointestinal, neurological and metabolic disorders, suggesting Trp metabolites/AhR signaling modulation as an interesting therapeutic perspective. In this review, we describe the most recent advances concerning Trp metabolism and AhR signaling in human health and disease, with a focus on nutrition as a potential therapy to modulate Trp metabolites acting on AhR. A better understanding of the complex balance between these pathways in human health and disease will yield therapeutic opportunities.

Cancer diets for cancer patients: Lessons from mouse studies and new insights from the study of fatty acid metabolism in tumors.

Specific diets for cancer patients have the potential to offer an adjuvant modality to conventional anticancer therapy. If the concept of starving cancer cells from nutrients to inhibit tumor growth is quite simple, the translation into the clinics is not straightforward. Several diets have been described including the Calorie-restricted diet based on a reduction in carbohydrate intake and the Ketogenic diet wherein the low carbohydrate content is compensated by a high fat intake. As for other diets that deviate from normal composition only by one or two amino acids, these diets most often revealed a reduction in tumor growth in mice, in particular when associated with chemo- or radiotherapy. By contrast, in cancer patients, the interest of these diets is almost exclusively supported by case reports precluding any conclusions on their real capacity to influence disease outcome. In parallel, the field of tumor lipid metabolism has emerged in the last decade offering a better understanding of how fatty acids are captured, synthesized or stored as lipid droplets in cancers. Fatty acids participate to cancer cell survival in the hypoxic and acidic tumor microenvironment and also support proliferation and invasiveness. Interestingly, while such addiction for fatty acids may account for cancer progression associated with high fat diet, it could also represent an Achilles heel for tumors. In particular n-3 polyunsaturated fatty acids represent a class of lipids that can exert potent cytotoxic effects in tumors and therefore represent an attractive diet supplementation to improve cancer patient outcomes.

The importance of enteral nutrition to prevent or treat undernutrition in children undergoing treatment for cancer.

Nutrition therapy is a therapeutic approach to treating medical conditions and symptoms via diet, which can be done by oral, enteral or parenteral routes. It is desirable to include nutritional interventions as a standard of care in pediatric cancer units (PCUs) at all levels of care. The interventions are dependent on available resources and personnel across all clinical settings. Enteral nutrition is easy, inexpensive, uses the gastrointestinal tract, maintains gut mucosal integrity, and allows for individualized nutritional strategies. This narrative review describes enteral nutritional interventions for children undergoing cancer treatment and is aimed at PCUs of all levels of care located in a low- and middle-income country.