Chlorogenic acid (CGA), an important biologically active dietary polyphenol, is produced by certain plant species and is a major component of coffee. Reduction in the risk of a variety of diseases ...following CGA consumption has been mentioned in recent basic and clinical research studies. This systematic review discusses in vivo animal and human studies of the physiological and biochemical effects of chlorogenic acids (CGAs) on biomarkers of chronic disease. We searched PubMed, Embase, Amed and Scopus using the following search terms: (“chlorogenic acid” OR “green coffee bean extract”) AND (human OR animal) (last performed on April 1st, 2015) for relevant literature on the in vivo effects of CGAs in animal and human models, including clinical trials on cardiovascular, metabolic, cancerogenic, neurological and other functions. After exclusion of editorials and letters, uncontrolled observations, duplicate and not relevant publications the remaining 94 studies have been reviewed. The biological properties of CGA in addition to its antioxidant and anti-inflammatory effects have recently been reported. It is postulated that CGA is able to exert pivotal roles on glucose and lipid metabolism regulation and on the related disorders, e.g. diabetes, cardiovascular disease (CVD), obesity, cancer, and hepatic steatosis. The wide range of potential health benefits of CGA, including its anti-diabetic, anti-carcinogenic, anti-inflammatory and anti-obesity impacts, may provide a non-pharmacological and non-invasive approach for treatment or prevention of some chronic diseases. In this study, the effects of CGAs on different aspects of health by reviewing the related literatures have been discussed.
The issue of placebo response and the extent of its effect on psychotherapy is complex for two specific reasons: i) Current standards for drug trials, e.g., true placebo interventions, ...double-blinding, cannot be applied to most psychotherapy techniques, and ii) some of the "nonspecific effects" in drug therapy have very specific effects in psychotherapy, such as the frequency and intensity of patient-therapist interaction. In addition, different psychotherapy approaches share many such specific effects (the "dodo bird verdict") and lack specificity with respect to therapy outcome. Here, we discuss the placebo effect in psychotherapy under four aspects: a) nonspecific factors shared with drug therapy (context factors); b) nonspecific factors shared among all psychotherapy traditions (common factors); c) specific placebo-controlled options with different psychotherapy modalities; and d) nonspecific control options for the specific placebo effect in psychotherapy. The resulting framework proposes that the exploration and enumeration of context factors, common factors, and specific factors contributes to the placebo effects in psychotherapy.
Accumulating evidence indicates that the gut microbiota communicates with the central nervous system, possibly through neural, endocrine, and immune pathways, and influences brain function. B. longum ...1714™ has previously been shown to attenuate cortisol output and stress responses in healthy subjects exposed to an acute stressor. However, the ability of B. longum 1714™ to modulate brain function in humans is unclear.
In a randomized, double-blinded, placebo-controlled trial, the effects of B. longum 1714™ on neural responses to social stress, induced by the "Cyberball game," a standardized social stress paradigm, were studied. Forty healthy volunteers received either B. longum 1714™ or placebo for 4 weeks at a dose of 1 × 10 cfu/d. Brain activity was measured using magnetoencephalography and health status using the 36-item short-form health survey.
B. longum 1714™ altered resting-state neural oscillations, with an increase in theta band power in the frontal and cingulate cortex (P < 0.05) and a decrease in beta-3 band in the hippocampus, fusiform, and temporal cortex (P < 0.05), both of which were associated with subjective vitality changes. All groups showed increased social stress after a 4-week intervention without an effect at behavioral level due to small sample numbers. However, only B. longum 1714™ altered neural oscillation after social stress, with increased theta and alpha band power in the frontal and cingulate cortex (P < 0.05) and supramarginal gyrus (P < 0.05).
B. longum 1714™ modulated resting neural activity that correlated with enhanced vitality and reduced mental fatigue. Furthermore, B. longum 1714™ modulated neural responses during social stress, which may be involved in the activation of brain coping centers to counter-regulate negative emotions.
Sex has been speculated to be a predictor of the placebo and nocebo effect for many years, but whether this holds true or not has rarely been investigated. We utilized a placebo literature database ...on various aspects of the genuine placebo/nocebo response. In 2015, we had extracted 75 systematic reviews, meta-analyses, and meta-regressions performed in major medical areas (neurology, psychiatry, internal medicine). These meta-analyses were screened for whether sex/gender differences had been noted to contribute to the placebo/nocebo effect: in only 3 such analyses female sex was associated with a higher placebo effect, indicating poor evidence for a contribution of sex to it in RCTs. This was updated with another set of meta-analyses for the current review, but did not change the overall conclusion. The same holds true for 18 meta-analyses investigating adverse event (nocebo) reporting in RCT in the placebo arm of trials. We also screened our database for papers referring to sex/gender and the placebo effect in experimental studies, and identified 28 papers reporting 29 experiments. Their results can be summarized as follows: (a) Despite higher sensitivity of pain in females, placebo analgesia is easier to elicit in males; (b) It appears that conditioning is effective specifically eliciting nocebo effects; (c) Conditioning works specifically well to elicit placebo and nocebo effects in females and with nausea; (d) Verbal suggestions are not sufficient to induce analgesia in women, but work in men. These results will be discussed with respect to the question why nausea and pain may be prone to be responsive to sex/gender differences, while other symptoms are less. Lastly, we will discuss the apparent discrepancy between RCT with low relevance of sex, and higher relevance of sex in specific experimental settings. We argue that the placebo response is predominantly the result of a conditioning (learning) response in females, while in males it predominantly may be generated via (verbal) manipulating of expectancies. In RCT therefore, the net outcome of the intervention may be the same despite different mechanisms generating the placebo effect between the sexes, while in experimental work when both pathways are separated and explicitly explored, such differences may surface.
Much has been written about the placebo effects in functional gastrointestinal disorders (FGD), especially in irritable bowel syndrome (IBS), driven by the early hypothesis that in randomized ...controlled trials (RCTs) of IBS, the placebo effect might be specifically high and thus, corrupts the efficacy of novel drugs developed for this condition. This narrative review is based on a specific search method, a database (
www.jips.online
) developed since 2004 containing more than 4,500 papers (data papers, meta-analyses, systematic reviews, reviews) pertinent to the topic placebo effects/placebo response. Three central questions—deducted from the body of current literature—are addressed to explore the evidence behind this hypothesis: What is the size placebo effect in FGD, especially in IBS, and is it different from the placebo effect seen in other gastrointestinal disorders? Is the placebo effect in FGD different from other functional, non-intestinal disorders,
e.g.
in other pain syndromes? Is the placebo effect in FGD related to placebo effects seen in psychiatry,
e.g.
in depression, anxiety disorders, and alike? Following this discussion, a fourth question is raised as the result of the three: What are the consequences of this for future drug trials in FGD? In summary it is concluded that, contrary to common belief and discussion, the placebo effect seen in RCT in FGD is not specifically high and extraordinary as compared to other comparable (
i.e.
functional) disorders. It shares less than expected commonalities with the placebo effect in psychiatry, and very few predictors have yet been identified that determine its effect size, especially some that are driven by design features of the studies. Current practice of RCT in IBS seems to limit and control the placebo effect quite well, and future trial practice,
e.g.
head-to-head trial, still offers options to maintain this control, even in the absence of placebos used.
Placebo and nocebo responses are mostly discussed in clinical trials with functional bowel disorders. Much less has been investigated and is known in gastrointestinal diseases beyond irritable bowel ...syndrome (IBS), especially in inflammatory bowel diseases (IBD). For the purpose of this review, we screened the Journal of Interdisciplinary Placebo Studies (JIPS) database with approximately 4,500 genuine placebo research articles and identified nine meta-analyses covering more than 135 randomized and placebo-controlled trials (RCTs) with more than 10,000 patients with Crohn´s disease (CD) and another five meta-analyses with 150 RCTs and more than 10,000 patients with ulcerative colitis (UC). Only three discussed nocebo effects, especially in the context of clinical use of biosimilars to treat inflammation. The articles were critically analyzed with respect to the size of the placebo response in CD and UC, its effects on clinical improvement versus maintenance of remission, and mediators and moderators of the response identified. Finally, we discussed and compared the differences and similarities of the placebo responses in IBD and IBS and the nocebo effect in switching from biologics to biosimilars in IBD management.
To systematically review the effects of probiotics on central nervous system function in animals and humans, to summarize effective interventions (species of probiotic, dose, duration), and to ...analyze the possibility of translating preclinical studies. Literature searches were conducted in Pubmed, Medline, Embase, and the Cochrane Library. Only randomized controlled trials were included. In total, 38 studies were included: 25 in animals and 15 in humans (2 studies were conducted in both). Most studies used
(eg,
,
, and
) and
(eg,
, and
), with doses between 10⁸ and 10¹⁰ colony-forming units for 2 weeks in animals and 4 weeks in humans. These probiotics showed efficacy in improving psychiatric disorder-related behaviors including anxiety, depression, autism spectrum disorder (ASD), obsessive-compulsive disorder, and memory abilities, including spatial and non-spatial memory. Because many of the basic science studies showed some efficacy of probiotics on central nervous system function, this background may guide and promote further preclinical and clinical studies. Translating animal studies to human studies has obvious limitations but also suggests possibilities. Here, we provide several suggestions for the translation of animal studies. More experimental designs with both behavioral and neuroimaging measures in healthy volunteers and patients are needed in the future.
Placebo effects are known for numerous clinical symptoms. Until recently, deception of placebos was thought to be essential for placebo effects, but intriguing new studies suggest that even placebos ...without concealment (open-label placebos) may help patients with various clinical disorders. Most of those studies compared open-label placebo treatments with no treatment conditions (or treatment "as usual"). Given that open-label placebo studies obviously cannot be blinded, additional control studies are important to assess the efficacy of open-label placebos. The current study aimed to fil this gap by comparing open-label with conventional double-blind placebos and treatment as usual. Patients with seasonal allergic rhinitis were randomly divided in different groups. The first group received open-label placebos, the second double-blind placebos, and the third was treated as usual. After 4 weeks, results demonstrated that open-label placebos improved allergic symptoms more than treatment-as-usual and even more as double-blind placebos. In addition, we observed that allergic symptoms in general (and also the open-label placebo effects) were reduced by the Covid-19 pandemic. The results suggest that seasonal allergic symptoms may be relieved by open-label placebos. We discuss these results by addressing possible different mechanisms of open-label and conventionally concealed placebo treatments.
Irritable bowel syndrome (IBS) is a heterogeneous functional disorder with a multifactorial etiology that involves the interplay of both host and environmental factors. Among environmental factors ...relevant for IBS etiology, the diet stands out given that the majority of IBS patients report their symptoms to be triggered by meals or specific foods. The diet provides substrates for microbial fermentation, and, as the composition of the intestinal microbiota is disturbed in IBS patients, the link between diet, microbiota composition, and microbial fermentation products might have an essential role in IBS etiology. In this review, we summarize current evidence regarding the impact of diet and the intestinal microbiota on IBS symptoms, as well as the reported interactions between diet and the microbiota composition. On the basis of the existing data, we suggest pathways (mechanisms) by which diet components, via the microbial fermentation, could trigger IBS symptoms. Finally, this review provides recommendations for future studies that would enable elucidation of the role of diet and microbiota and how these factors may be (inter)related in the pathophysiology of IBS.
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