The Molecular Link from Diet to Cancer Cell Metabolism.

Malignant cells remodel their metabolism to meet the demands of uncontrolled cell proliferation. These demands lead to differential requirements in energy, biosynthetic precursors, and signaling intermediates. Both genetic programs arising from oncogenic events and transcriptional programs and epigenomic events are important in providing the necessary metabolic network activity. Accumulating evidence has established that environmental factors play a major role in shaping cancer cell metabolism. For metabolism, diet and nutrition are the major environmental aspects and have emerged as key components in determining cancer cell metabolism. In this review, we discuss these emerging concepts in cancer metabolism and how diet and nutrition influence cancer cell metabolism.

Eating during the Hemodialysis Session: A Practice Improving Nutritional Status or a Risk Factor for Intradialytic Hypotension and Reduced Dialysis Adequacy?

Historically, eating during the hemodialysis treatment has been associated with increased risk for adverse intradialytic symptoms and events, risks that have resulted in the implementation of restrictive in-center nutrition policies. Recent studies, however, have recorded a shift in clinical practice with a higher proportion of physicians following the view that administration of intradialytic meals and supplements represents a simple and effective approach to enhance caloric intake and improve nutritional status among patients on hemodialysis. This shift towards less restrictive in-center nutrition practices is mainly supported by evidence from observational studies associating intradialytic nutritional supplementation with improvements in protein-energy wasting, inflammatory state, and health-related quality of life. In sharp contrast, earlier and recent interventional studies have documented that feeding during the hemodialysis treatment provokes a rapid postprandial decline in blood pressure and raises the incidence of symptomatic intradialytic hypotension. Furthermore, other studies have shown that postprandial redistribution in intravascular volume and enhanced blood supply to the gastrointestinal circulation may interfere with the adequacy of the delivered hemodialysis. Those who defend the position that intradialytic nutritional support is beneficial do not dispute the physiology of postprandial hemodynamic response, but they argue against its clinical significance. In this article, we provide an overview of studies that explored the effect of eating during the hemodialysis treatment on intradialytic hemodynamic stability and adequacy of the delivered hemodialysis. We reason that these risks have important clinical implications that are not counteracted by anticipated benefits of this strategy on caloric intake and nutritional status.

Physiological changes after spa treatment - a focus on endocrinology.

The paper presents the results of our effort to reveal objective parameters for evaluation of the spa treatment for patients with anxiety-depressive disorders. The study was based on our previous experience with neuroactive steroids and neurosteroids, which play a crucial role in the psychological well-being of patients by maintaining balance of the organism. A total number of 94 steroids were determinated in a group of 70 female patients diagnosed with anxiety-depressive disorders. Patients underwent a month spa treatment while maintaining unchanged medication dosing with SSRI (selective serotonin reuptake inhibitors). The other investigated factors contributing to improving the health of treated subjects were amino-acid homocysteine and serotonin. The blood samples were collected at the beginning and the end of the spa treatment. Serotonin in all patients increased by a relative 23 % (results given as relative differences in percent), while homocysteine decreased by 17.1 %. Statistically significant increases were found in 21 steroids, which indicate activation of the adrenal cortex. It can be assumed, that the overall improvement in the mental condition of patients, which was proved by questionnaire from Knobloch and Hausner, the increase in immune suppressive substances and anti-autoimmune responses, will maintain for a longer time after the spa treatment.

Diets, functional foods, and nutraceuticals as alternative therapies for inflammatory bowel disease: Present status and future trends.

Inflammatory bowel disease (IBD) is a serious health concern among western societies. The disease is also on the rise in some East Asian countries and in Australia. Health professionals and dietitians around the world are facing an unprecedented challenge to prevent and control the increasing prevalence of IBD. The current therapeutic strategy that includes drugs and biological treatments is inefficient and are associated with adverse health consequences. In this context, the use of natural products is gaining worldwide attention. In vivo studies and clinical evidence suggest that well-planned dietary regimens with specific nutrients can alleviate gastrointestinal inflammation by modulating inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin 1 (IL-1), IL-6, IL-1ß, and IL-10. Alternatively, the avoidance of high-fat and high-carbohydrate diets is regarded as an effective tool to eliminate the causes of IBD. Many functional foods and bioactive components have received attention for showing strong therapeutic effects against IBD. Both animal and human studies suggest that bioactive functional foods can ameliorate IBD by downregulating the pro-inflammatory signaling pathways, such as nuclear factor κB, STAT1, STAT6, and pro-inflammatory cytokines, including IL-1ß, IL-4, IL-6, COX-2, TNF-α, and interferon γ. Therefore, functional foods and diets have the potential to alleviate IBD by modulating the underlying pathogenic mechanisms. Future comprehensive studies are needed to corroborate the potential roles of functional foods and diets in the prevention and control of IBD.

Inflammageing and metaflammation: The yin and yang of type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is characterised by chronic low-grade inflammation, recently referred to as 'metaflammation', a relevant factor contributing to the development of both diabetes and its complications. Nonetheless, 'canonical' anti-inflammatory drugs do not yield satisfactory results in terms of prevention of diabetes progression and of cardiovascular events, suggesting that the causal mechanisms fostering metaflammation deserve further research to identify new druggable targets. Metaflammation resembles ageing-induced low-grade inflammation, previously referred to as inflammageing, in terms of clinical presentation and the molecular profile, pointing to a common aetiology for both conditions. Along with the mechanisms proposed to fuel inflammageing, here we dissect a plethora of pathological cascades triggered by gluco- and lipotoxicity, converging on candidate phenomena possibly explaining the enduring pro-inflammatory program observed in diabetic tissues, i.e. persistent immune-system stimulation, accumulation of senescent cells, epigenetic rearrangements, and alterations in microbiota composition. We discuss the possibility of harnessing these recent discoveries in future therapies for T2DM. Moreover, we review recent evidence regarding the ability of diets and physical exercise to modulate selected inflammatory pathways relevant for the diabetic pathology. Finally, we examine the latest findings showing putative anti-inflammatory mechanisms of anti-hyperglycaemic agents with proven efficacy against T2DM-induced cardiovascular complications, in order to gain insights into quickly translatable therapeutic approaches.

Nutritional Psychiatry: Where to Next?

The nascent field of 'Nutritional Psychiatry' offers much promise for addressing the large disease burden associated with mental disorders. A consistent evidence base from the observational literature confirms that the quality of individuals' diets is related to their risk for common mental disorders, such as depression. This is the case across countries and age groups. Moreover, new intervention studies implementing dietary changes suggest promise for the prevention and treatment of depression. Concurrently, data point to the utility of selected nutraceuticals as adjunctive treatments for mental disorders and as monotherapies for conditions such as ADHD. Finally, new studies focused on understanding the biological pathways that mediate the observed relationships between diet, nutrition and mental health are pointing to the immune system, oxidative biology, brain plasticity and the microbiome-gut-brain axis as key targets for nutritional interventions. On the other hand, the field is currently limited by a lack of data and methodological issues such as heterogeneity, residual confounding, measurement error, and challenges in measuring and ensuring dietary adherence in intervention studies. Key challenges for the field are to now: replicate, refine and scale up promising clinical and population level dietary strategies; identify a clear set of biological pathways and targets that mediate the identified associations; conduct scientifically rigorous nutraceutical and 'psychobiotic' interventions that also examine predictors of treatment response; conduct observational and experimental studies in psychosis focused on dietary and related risk factors and treatments; and continue to advocate for policy change to improve the food environment at the population level.

Neuro-nutraceuticals: The path to brain health via nourishment is not so distant.

In this Special Issue on "Nutraceuticals: Molecular and Functional Insights into how Natural Products Nourish the Brain", the editors bring together contributions from experts in nutraceutical research to provide a contemporary overview of how select chemically identified molecules can beneficially affect brain function at the molecular level. Other contributions address key emergent issues such as bioavailability, formulation, blood brain permeability, neuronal health and inflammation that impact upon how nutraceuticals ultimately leverage the brain to function better. Whilst nutraceutical is used as marketing term, it has no regulatory definition, and there is a continuing need for licensing authorities to ensure that adequate guidelines exist pertinent to the safety to guide consumers internationally. In terms of the benefit of nutraceuticals is it clear that some naturally occurring molecules can be advantageous to both the young and aged brain, and that they have actions that ultimately can be directed to aid either in the improvement of cognition or in the management of debilitating neurodegenerative and neuropsychiatric conditions.

Resonance Raman spectroscopic evaluation of skin carotenoids as a biomarker of carotenoid status for human studies.

Resonance Raman spectroscopy (RRS) is a non-invasive method that has been developed to assess carotenoid status in human tissues including human skin in vivo. Skin carotenoid status has been suggested as a promising biomarker for human studies. This manuscript describes research done relevant to the development of this biomarker, including its reproducibility, validity, feasibility for use in field settings, and factors that affect the biomarker such as diet, smoking, and adiposity. Recent studies have evaluated the response of the biomarker to controlled carotenoid interventions, both supplement-based and dietary [e.g., provision of a high-carotenoid fruit and vegetable (F/V)-enriched diet], demonstrating consistent response to intervention. The totality of evidence supports the use of skin carotenoid status as an objective biomarker of F/V intake, although in the cross-sectional setting, diet explains only some of the variation in this biomarker. However, this limitation is also a strength in that skin carotenoids may effectively serve as an integrated biomarker of health, with higher status reflecting greater F/V intake, lack of smoking, and lack of adiposity. Thus, this biomarker holds promise as both a health biomarker and an objective indicator of F/V intake, supporting its further development and utilization for medical and public health purposes.

Has the use of complementary and alternative medicine therapies by U.S. adults with chronic disease-related functional limitations changed from 2002 to 2007?

OBJECTIVES: This study examined changes in the use of complementary and alternative medicine (CAM) therapies by U.S. adults aged 18 years or older with chronic disease-related functional limitations between 2002 and 2007. DESIGN: The study was a cross-sectional survey. SETTING/LOCATION: The study was conducted in the United States. SUBJECTS: The study comprised adults aged 18 years or older with chronic disease-related functional limitations. METHODS: Data were obtained from the 2002 and 2007 U.S. National Health Interview Survey to compare the use of 22 CAM therapies (n=9313 and n=7014, respectively). Estimates were age adjusted to the year 2000 U.S. standard population. RESULTS: The unadjusted and age-standardized prevalence of overall CAM use (22 therapies comparable between both survey years) was higher in 2007 than in 2002 (30.6% versus 26.9%, p<0.001 and 34.4% versus 30.6%, p<0.001, respectively). Adults with functional limitations that included changing and maintaining body position experienced a significant increase in CAM use between 2002 and 2007 (31.1%-35.0%, p<0.01). The use of deep breathing exercises was the most prevalent CAM therapy in both 2002 and 2007 and increased significantly during this period (from 17.9% to 19.9%, p<0.05). The use of meditation, massage, and yoga also increased significantly from 2002 and 2007 (11.0%-13.5%, p<0.01; 7.0%-10.9%, p<0.0001; and 5.1% to 6.6%, p<0.05, respectively), while the use of the Atkins diet decreased (2.2%- 1.4%, p<0.01). CONCLUSIONS: Among U.S. adults with chronic disease-related functional limitations, the overall increase in CAM use from 2002 to 2007 was significant, particularly among those with changing and maintaining body position limitations.

Dietary therapy for patients with hypocitraturic nephrolithiasis.

Citrate is an inhibitor of urinary stone formation. Clinical and in vitro data suggest that increasing urine citrate levels will decrease the precipitation of calcium stones. Historically, low urinary citrate has been treated with oral potassium citrate or sodium citrate supplementation, but recent studies have shown the potential of dietary interventions to raise urine citrate levels. Dietary therapy with commercial or homemade beverages is attractive to patients who would prefer nonpharmacological intervention. To date, several drinks have shown promise but no single beverage has been found to consistently raise urine citrate levels in a reproducible fashion. Further research is necessary to develop the ideal dietary therapy for hypocitraturic calcium nephrolithiasis.

Fitoestrógenos y sus efectos sobre la osteoporosis en la mujer posmenopáusica / Phytoestrogens and their effects on osteoporosis in postmenopausal women

Los fitoestrógenos son sustancias de origen vegetal con efecto estrogénico débil, de inhibición enzimática y antioxidante. Desde un punto de vista clínico, se han barajado como una alternativa de tratamiento en la mujer menopáusica y sus síntomas asociados. Teniendo en cuenta que los estrógenos son los principales responsables del mantenimiento de la masa ósea en la mujer, inhibiendo la resorción ósea a través de su interacción con los osteoblastos, la reducción de sus niveles durante la menopausia constituirá un factor de riesgo para el desarrollo de osteoporosis en la mujer posmenopáusica. En este sentido, cabe plantearse si la terapia con fitoestrógenos constituye o no una herramienta terapéutica por su potencial efecto estrogénico en la prevención de la osteoporosis posmenopáusica. El objetivo de este trabajo ha sido proporcionar una revisión amplia y precisa acerca de la evidencia científica existente por el momento en torno al papel de los fitoestrógenos en la prevención de la osteoporosis en la mujer posmenopáusica y sus implicaciones en la clínica (AU)

Phytoestrogens are plant substances with a weak estrogenic effect, an enzyme inhibitory effect and antioxidant activity. The possibility of using them for menopause associated symptoms has been entertained. Given that estrogens are primarily responsible for maintaining bone mass in women by inhibiting bone resorption through their interaction with osteoblasts, reducing estrogen levels during menopause constitutes a risk factor for developing osteoporosis in postmenopausal women. In view of this, the question arises as to whether phytoestrogens, due to their potential estrogenic effect, constitute or not a therapeutic tool in the prevention of postmenopausal osteoporosis. The aim of this study was to provide a comprehensive, accurate review on the available scientific evidence regarding the role of phytoestrogens in preventing osteoporosis in postmenopausal women and its implications in clinical practice (AU)

Central nervous system nutrient signaling: the regulation of energy balance and the future of dietary therapies.

The mammalian target of rapamycin (mTOR) pathway coordinates cell growth in response to nutrient availability. Increasing evidence points to a role for mTOR to also direct whole-body energy balance in response to micronutrient as well as hormonal cues. This positions mTOR as a key central integrator of acute and chronic changes in fuel status. Energy balance is affected by mTOR in several organ systems, including the hypothalamus, where the pathway can modulate feeding. We propose that a greater understanding of this nutrient-sensitive pathway may open the door to more intelligent, effective diet design based on the effects of micronutrients on specific signaling pathways.

Vitamin D and the adaptive immune system with special emphasis to allergic reactions and allograft rejection.

Tolerance induction is a fascinating option to prevent allergic diseases or allograft rejection. Calcitriol is the hormonal form of vitamin D and is produced by two hydroxylation steps: a hepatic 25-hydroxylation of vitamin D and a subsequent renal 1alpha-hydroxylation. Calcitriol has important immunomodulatory properties. Calcitriol can prevent those inflammatory processes which are responsible for allograft rejection, whereas its effects on immunological responses related to allergic reactions are more complex and not fully elucidated. This article summarizes present knowledge on vitamin D and the adaptive immune system. Experimental and clinical studies support the assumption that calcitriol can decrease the risk of allograft rejection. Prospective randomized clinical trials are however needed to clarify whether administration of calcitriol, some of its analogues, or simple vitamin D supplementation is able to prevent rejection in solid organ transplanted patients. With respect to allergic reactions, human data are inconsistent at present. Some argue that vitamin D deficiency may cause allergic reactions whereas others argue that vitamin D excess leads to an increased allergy risk. In this context, current strategy of vitamin D supplementation in infants and the possibility of a bimodal effect on allergic reactions of both, vitamin D deficiency and excess are discussed.

Long-term impact of an antioxidant-deficient neonatal diet on lipid and glucose metabolism.

Newborn infants are at risk for oxidative stress leading to metabolic syndrome features. Oxidative stress can be induced by oxidant load such as oxygen supplementation, peroxides from intravenous nutrition, or low antioxidant defenses. We hypothesize that a modulation of antioxidant defenses during the neonatal period, without external oxidant challenge, will have a long-term influence on energy metabolism. Guinea pigs were fed between their third and their seventh day of life a regular chow leading to "mature" antioxidant defenses or a deficient chow leading to lower antioxidant defenses. Between weeks 1 and 14, the animals were fed regular chow. The hepatic oxidized redox status of glutathione associated with the deficient diet (-221 +/- 2 vs -228 +/- 1 mV, p < 0.01) was maintained until 14 weeks. At 13-14 weeks, animals fed the deficient diet presented lower plasma TG (479 +/- 57 vs 853 +/- 32 microM, p < 0.01), lower blood glucose (5.8 +/- 0.3 vs 6.9 +/- 0.3 mM, p < 0.05), and better tolerance to glucose (p < 0.05). Blood glucose correlated negatively with the redox status (r2 = 0.47, p < 0.01). Low antioxidant defenses during the neonatal period induce a better energy substrate profile associated with an oxidized redox status later in life. These findings suggest being aware of negative consequences when adopting "aggressive" antioxidant therapies in newborn infants.

Diet and Alzheimer's disease.

Alzheimer's disease (AD) is increasing in prevalence. There are no known preventive or curative measures. There is evidence that oxidative stress, homo-cysteine-related vitamins, fats, and alcohol have a role in the pathogenesis of AD. Some epidemiologic studies suggest that higher dietary intake of antioxidants, vitamins B(6), B(12), and folate, unsaturated fatty acids, and fish are related to a lower risk of AD, but reports are inconsistent. Modest to moderate alcohol intake, particularly wine, may be related to a lower risk of AD. The Mediterranean diet may also be related to lower AD risk. However, randomized clinical trials of supplements of vitamins E, B(12), B(6), and folate have shown no cognitive benefit, and randomized trials for other nutrients or diets in AD are not available. The existing evidence does not support the recommendation of specific supplements, foods, or diets for the prevention of AD.

[History and importance of functional foods]. / Geschichte und Bedeutung von Functional Foods.

A short overview on the historic developments is presented which resulted in a scientific consensus on the concept of functional food in 1999. The preconditions to be fulfilled by the functional foods are summarized. It is emphasized that easy measurable biological markers that are relevant for the expected health benefits may be important for measuring the effectiveness of the action of a functional food. Of special importance is also the recently published scientific consensus paper on the kind of experimental results that should be made available for the official acceptance of a claim. These proposals are at present serving as guidelines in the ongoing deliberations on the legislation for claims by the European Union.

Influencia de la dieta en la salud ósea / Influence of diet on bone health

En conclusión, es difícil determinar en qué medida la dieta es responsable del mantenimiento de la salud de la población. Las recomendaciones nutricionales pretenden prevenir el desarrollo de enfermedades crónicas y degenerativas, con el fin de promocionar la salud de los individuos. En este contexto nace la idea de dieta sana para el mantenimiento, entre otros, de la salud ósea. Hasta la fecha no existe una evidencia científica definitiva para establecer recomendaciones firmes en la relación dieta y salud ósea, con la excepción del calcio y la vitamina D. En el caso del calcio, se deben recomendar suplementos del mineral en poblaciones con ingesta inferior a 400-500 mg/día. Por el momento, se necesitan más estudios para establecer si el aumento de la ingesta de calcio en individuos con dietas suficientes y en poblaciones con bajo riesgo de fractura supone un beneficio adicional para el hueso. Con respecto a la vitamina D, la evidencia demuestra que los individuos a riesgo de presentar déficit, como son los ancianos que viven en residencias, deben recibir suplementos orales de esta vitamina. Sin embargo, se desconoce en el momento actual si mejorar el estado de esta vitamina en estos grupos vulnerables es una estrategia poblacional eficaz para prevenir la osteoporosis en el futuro. Para el resto de los componentes de la dieta, su relación con la salud ósea permanece en discusión. Las recomendaciones de dieta adecuada para promocionar la salud y evitar las enfermedades crónicas también son válidas para la osteoporosis. Estas medidas incluyen el consumo habitual de fruta, verdura y productos lácteos, sustituir la carne por productos de granja, pescado y legumbres, y reducir el contenido de sal, café y alcohol de la dieta(AU)

In conclusion, it is difficult to determine to what degree diet is responsible for health maintenance of the population. Nutritional recommendations aim to prevent the development of chronic and degenerative diseases in order to promote the individual's health. The idea of a healthy diet for maintenance, among others, of bone health arises in this context. Up to now, there is no definitive scientific evidence to establish firm recommendations on the diet and bone health relationship, except for calcium and vitamin D. In the case of calcium, mineral supplements should be recommended in populations with intake less than 400-500 mg/day. At present, more studies are needed to establish if the increase of calcium intake in individuals with sufficient diets and in populations with low risk of fracture mean an additional benefit for the bone. In regards to vitamin D, the evidence demonstrates that individuals at risk of having a deficit, as the elderly who live in residences, should receive oral supplements of this vitamin. However, at present, it is unknown if improving the state of this vitamin in these vulnerable groups is an effective populational strategy to prevent osteoporosis in the future. For the rest of the diet components, their relationship with bone health is still under debate. Recommendations of adequate diet to promote health and avoid chronic diseases are also valid for osteoporosis. These measures include usual intake of fruit, vegetables and lactic products, substitute mean with farm products, fish and pod vegetables and reducing salt content, coffee and alcohol in the diet(AU)