No abstract

Nutrition research is struggling to demonstrate beneficial health effects, since nutritional effects are often subtle and long term. Health has been redefined as the ability of our body to cope with daily-life challenges. Physiology acts as a well-orchestrated machinery to adapt to the continuously changing environment. We term this adaptive capacity “phenotypic flexibility.” The phenotypic flexibility concept implies that health can be measured by the ability to adapt to conditions of temporary stress, such as physical exercise, infections or mental stress, in a healthy manner. This may offer a more sensitive way to assess changes in health status of healthy subjects. Here, we performed a systematic review of 61 studies applying different nutritional stress tests to quantify health and nutritional health effects, with the objective to define an optimal nutritional stress test that has the potential to be adopted as the golden standard in nutrition research. To acknowledge the multi-target role of nutrition, a relevant subset of 50 processes that govern optimal health, with high relevance to diet, was used to define phenotypic flexibility. Subsequently, we assessed the response of biomarkers related to this subset of processes to the different challenge tests. Based on the obtained insights, we propose a nutritional stress test composed of a high-fat, high-caloric drink, containing 60 g palm olein, 75 g glucose and 20 g dairy protein in a total volume of 400 ml. The use of such a standardized nutritional challenge test in intervention studies is expected to demonstrate subtle improvements of phenotypic flexibility, thereby enabling substantiation of nutritional health effects.Electronic supplementary materialThe online version of this article (doi:10.1007/s12263-015-0459-1) contains supplementary material, which is available to authorized users.

ObjectiveThe aim is to characterize subgroups or phenotypes of rheumatoid arthritis (RA) patients using a systems biology approach. The discovery of subtypes of rheumatoid arthritis patients is an essential research area for the improvement of response to therapy and the development of personalized medicine strategies.MethodsIn this study, 39 RA patients are phenotyped using clinical chemistry measurements, urine and plasma metabolomics analysis and symptom profiles. In addition, a Chinese medicine expert classified each RA patient as a Cold or Heat type according to Chinese medicine theory. Multivariate data analysis techniques are employed to detect and validate biochemical and symptom relationships with the classification.ResultsThe questionnaire items ‘Red joints’, ‘Swollen joints’, ‘Warm joints’ suggest differences in the level of inflammation between the groups although c-reactive protein (CRP) and rheumatoid factor (RHF) levels were equal. Multivariate analysis of the urine metabolomics data revealed that the levels of 11 acylcarnitines were lower in the Cold RA than in the Heat RA patients, suggesting differences in muscle breakdown. Additionally, higher dehydroepiandrosterone sulfate (DHEAS) levels in Heat patients compared to Cold patients were found suggesting that the Cold RA group has a more suppressed hypothalamic-pituitary-adrenal (HPA) axis function.ConclusionSignificant and relevant biochemical differences are found between Cold and Heat RA patients. Differences in immune function, HPA axis involvement and muscle breakdown point towards opportunities to tailor disease management strategies to each of the subgroups RA patient.

RA patients could be divided in 2 groups according to CM theory. Molecular differences between the RA Cold and RA Heat groups were found which suggest differences in apoptotic activity. Subgrouping of patients according to CM diagnosis has the potential to provide opportunities for better treatment outcomes by targeting Western or CM treatment to specific groups of patients.

Introduction !The health care system in Western societies and one of its pillars, modern medicine, are increasingly under debate. The increasing costs of health care are reaching the level where it will not be sustainable in the near future. Recent estimates for the US health care system show an increase from 17% of the gross domestic product (GDP) in 2009 to over 20 % of the GDP in 2018, when the total cost will reach US $ 4.35 trillion [1]. At the same time, hopes for developing medicines that are more effective are fading away, since the pharmaceutical industry produces fewer new chemical entities (NCEʼs) that reach the market every year. In this era, crucial global issues have surfaced in various domains, including the financial, ecological, political, educational, religious/spiritual, and social realms. Mechanisms that previously functioned effectively must be replaced by new approaches. These challenges are not local, but global, and system thinking will be mandatory in the future. In such times of change, one must reflect and focus on the driving force of the system that needs to evolve. In health care, there must be a shift from an emphasis on economics, technological developments and political agendas back to a patient-centred health care environment. In health care, the paradigm of system thinking has emerged as systems biology. It is limiting to develop interventions on how a single compound interacts with a single target that is linked to a specific symptom. This "one-drug-fits-all" paradigm has shifted to an idea that patients require personalized medicines. Some successful examples have been used to treat cancer, including Herceptin ® (trastuzumab), Gleevec ® (imatinib mesylaat) and Iressa ® (gefitinib). However, a thorough systems approach has not yet been applied to design new drugs. Moreover, the patient is not yet seen as a unique individual. Treatments focus on a disease or a disease phenotype rather than the person, even though effective treatments rely on a proper systems diagnosis. In this paper, we describe how the global nature of challenges must be recognized to develop global solutions. These solutions must integrate diverse concepts and intuition to bring about a Abstract ! Innovative systems approaches to develop medicine and health care are emerging from the integration of Chinese and Western medicine strategies, philosophies and practices. The two medical systems are highly complementary as the reductionist aspects of Western medicine are favourable in acute disease situations and the holistic aspects of Chinese medicine offer more opportunities in chronic conditions and for prevention. In this article we argue that diagnosis plays a key role in building the bridge between Chinese and Western medicine. Recent advances in the study of health, healing, placebo effects and patientphysician interactions will be discussed pointing out the development of a system-based diagnosis. Especially, a system biology-based diagnosis can be used to capture phenotype information, leading towards a s...