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Treat more than heat-New therapeutic implications of Cimicifuga racemosa through AMPK-dependent metabolic effects.
Drewe, J, Boonen, G, Culmsee, C
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2022;:154060
Abstract
BACKGROUND Cimicifuga racemosa extracts (CRE) have obtained a "well-established use status" in the treatment of postmenopausal (i.e., climacteric) complaints, which predominantly include vasomotor symptoms such as hot flushes and sweating, as well as nervousness, irritability, and metabolic changes. Although characteristic postmenopausal complaints are known for a very long time and the beneficial effects of CRE on climacteric symptoms are well accepted, both the pathophysiology of postmenopausal symptoms and the mechanism of action of CREs are not yet fully understood. In particular, current hypotheses suggest that changes in the α-adrenergic and serotonergic signaling pathways secondary to estrogen depletion are responsible for the development of hot flushes. PURPOSE Some of the symptoms associated with menopause cannot be explained by these hypotheses. Therefore, we attempted to extend our classic understanding of menopause by integrating of partly age-related metabolic impairments. METHODS A comprehensive literature survey was performed using the PubMed database for articles published through September 2021. The following search terms were used: (cimicifuga OR AMPK) AND (hot flush* OR hot flash* OR menopaus* OR osteoporos* OR cancer OR antioxida* OR cardiovasc*). No limits were set with respect to language, and the references cited in the articles retrieved were used to identify additional publications. RESULTS We found that menopause is a manifestation of the general aging process, with specific metabolic changes that aggravate menopausal symptoms, which are accelerated by estrogen depletion and associated neurotransmitter dysregulation. Cimicifuga extracts with their metabolic effects mitigate climacteric symptoms but may also modulate the aging process itself. Central to these effects are effects of CRE on the metabolic key regulator, the AMP-activated protein kinase (AMPK). CONCLUSIONS As an extension of this effect dimension, other off-label indications may appear attractive in the sense of repurposing of this herbal treatment.
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Absorption and Metabolism of the Natural Sweeteners Erythritol and Xylitol in Humans: A Dose-Ranging Study.
Bordier, V, Teysseire, F, Senner, F, Schlotterbeck, G, Drewe, J, Beglinger, C, Wölnerhanssen, BK, Meyer-Gerspach, AC
International journal of molecular sciences. 2022;(17)
Abstract
The natural sweeteners erythritol and xylitol might be helpful to reduce sugar consumption and therefore prevent obesity and diabetes. The aim of the present study was to determine the absorption and metabolization into erythronate of different concentrations of erythritol and xylitol. Seventeen healthy lean participants received intragastric solutions of 10, 25, or 50 g erythritol or 7, 17, or 35 g xylitol on three study days in a randomized order. The study was double blinded with respect to the doses administered. We assessed plasma concentrations of erythritol, xylitol, and erythronate at fixed time intervals after administration with gas chromatography-mass spectrometry. We found: (i) a dose-dependent and saturable absorption of erythritol, (ii) a very low absorption of xylitol, (iii) a dose-dependent metabolization of erythritol into erythronate, and (iv) no metabolization of xylitol into erythronate. The implications of the metabolization of erythritol into erythronate for human health remain to be determined and more research in this area is needed.
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Comparative Effects of Metamizole (Dipyrone) and Naproxen on Renal Function and Prostacyclin Synthesis in Salt-Depleted Healthy Subjects - A Randomized Controlled Parallel Group Study.
Blaser, LS, Duthaler, U, Bouitbir, J, Leuppi-Taegtmeyer, AB, Liakoni, E, Dolf, R, Mayr, M, Drewe, J, Krähenbühl, S, Haschke, M
Frontiers in pharmacology. 2021;:620635
Abstract
Aim: The objective was to investigate the effect of metamizole on renal function in healthy, salt-depleted volunteers. In addition, the pharmacokinetics of the four major metamizole metabolites were assessed and correlated with the pharmacodynamic effect using urinary excretion of the prostacyclin metabolite 6-keto-prostaglandin F1α. Methods: Fifteen healthy male volunteers were studied in an open-label randomized controlled parallel group study. Eight subjects received oral metamizole 1,000 mg three times daily and seven subjects naproxen 500 mg twice daily for 7 days. All subjects were on a low sodium diet (50 mmol sodium/day) starting 1 week prior to dosing until the end of the study. Glomerular filtration rate was measured using inulin clearance. Urinary excretion of sodium, potassium, creatinine, 6-keto-prostaglandin F1α, and pharmacokinetic parameters of naproxen and metamizole metabolites were assessed after the first and after repeated dosing. Results: In moderately sodium-depleted healthy subjects, single or multiple dose metamizole or naproxen did not significantly affect inulin and creatinine clearance or sodium excretion. Both drugs reduced renal 6-keto-prostaglandin F1α excretion after single and repeated dosing. The effect started 2 h after intake, persisted for the entire dosing period and correlated with the concentration-profile of naproxen and the active metamizole metabolite 4-methylaminoantipyrine (4-MAA). PKPD modelling indicated less potent COX-inhibition by 4-MAA (EC50 0.69 ± 0.27 µM) compared with naproxen (EC50 0.034 ± 0.033 µM). Conclusions: Short term treatment with metamizole or naproxen has no significant effect on renal function in moderately sodium depleted healthy subjects. At clinically relevant doses, 4-MAA and naproxen both inhibit COX-mediated renal prostacyclin synthesis.
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Gastric emptying of solutions containing the natural sweetener erythritol and effects on gut hormone secretion in humans: A pilot dose-ranging study.
Wölnerhanssen, BK, Drewe, J, Verbeure, W, le Roux, CW, Dellatorre-Teixeira, L, Rehfeld, JF, Holst, JJ, Hartmann, B, Tack, J, Peterli, R, et al
Diabetes, obesity & metabolism. 2021;23(6):1311-1321
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Plain language summary
In recent years, erythritol, a non-calorie sweetener, has gained popularity due to the rise in obesity and Type 2 diabetes worldwide. The purpose of this randomised, placebo-controlled, double-blind, cross-over trial was to assess the effects of erythritol on the release of gut hormones, speed of gastric emptying, and the release of glucagon, motilin, and glucose-dependent insulinotropic polypeptide after erythritol administration. Erythritol in doses of ten, twenty-five, and fifty grams was well tolerated by the participants. The administration of erythritol induced a statistically significant dose-dependent stimulation of gut hormones such as plasma cholecystokinin, active glucagon‐like peptide‐1 and peptide tyrosine. Compared to the placebo, participants had slower gastric emptying with erythritol. Erythritol had no effect on the levels of motilin, glucose-dependent insulinotropic polypeptide, blood glucose, insulin, glucagon, blood lipids, or uric acid. Erythritol should be evaluated in larger, robust studies to determine whether it improves glycaemic control. However, healthcare professionals can use the results of this study to understand the potential uses of erythritol in the management of obesity and type 2 diabetes.
Abstract
AIM: To determine whether a dose-dependent effect in the stimulation of gut hormone release (plasma cholecystokinin [CCK], active glucagon-like peptide-1 [aGLP-1] and peptide tyrosine tyrosine [PYY]) is found for the natural sweetener erythritol. MATERIALS AND METHODS Twelve healthy, lean volunteers received solutions with 10, 25 or 50 g erythritol, or tap water enriched with 13 C-sodium acetate on four study days via a nasogastric tube in this randomized (active treatments), placebo-controlled, double-blind, cross-over trial. Blood samples and breath samples (13 C-sodium acetate method for measurement of gastric emptying [GE]) were taken at regular intervals, and sensations of appetite and gastrointestinal symptoms were rated. RESULTS We found (a) a dose-dependent stimulation of CCK, aGLP-1 and PYY, and slowing of GE, (b) no effect on blood glucose, insulin, motilin, glucagon or glucose-dependent insulinotropic polypeptide, (c) no effect on blood lipids and uric acid, and (d) no abdominal pain, nausea or vomiting. CONCLUSIONS Solutions with 10 and 50 g of erythritol stimulated gut hormone release. Emptying of erythritol-containing solutions from the stomach was slower compared with placebo. There was no effect on plasma glucose, insulin, glucagon, blood lipids or uric acid. All doses were well tolerated.
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Effect of the Natural Sweetener Xylitol on Gut Hormone Secretion and Gastric Emptying in Humans: A Pilot Dose-Ranging Study.
Meyer-Gerspach, AC, Drewe, J, Verbeure, W, Roux, CWL, Dellatorre-Teixeira, L, Rehfeld, JF, Holst, JJ, Hartmann, B, Tack, J, Peterli, R, et al
Nutrients. 2021;(1)
Abstract
Sugar consumption is associated with a whole range of negative health effects and should be reduced and the natural sweetener xylitol might be helpful in achieving this goal. The present study was conducted as a randomized, placebo-controlled, double-blind, cross-over trial. Twelve healthy, lean volunteers received intragastric solutions with 7, 17 or 35 g xylitol or tap water on four separate days. We examined effects on: gut hormones, glucose, insulin, glucagon, uric acid, lipid profile, as well as gastric emptying rates, appetite-related sensations and gastrointestinal symptoms. We found: (i) a dose-dependent stimulation of cholecystokinin (CCK), active glucagon-like peptide-1 (aGLP-1), peptide tyrosine tyrosine (PYY)-release, and decelerated gastric emptying rates, (ii) a dose-dependent increase in blood glucose and insulin, (iii) no effect on motilin, glucagon, or glucose-dependent insulinotropic peptide (GIP)-release, (iv) no effect on blood lipids, but a rise in uric acid, and (v) increased bowel sounds as only side effects. In conclusion, low doses of xylitol stimulate the secretion of gut hormones and induce a deceleration in gastric emptying rates. There is no effect on blood lipids and only little effect on plasma glucose and insulin. This combination of properties (low-glycemic sweetener which stimulates satiation hormone release) makes xylitol an attractive candidate for sugar replacement.
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Effect of the fixed combination of valerian, lemon balm, passionflower, and butterbur extracts (Ze 185) on the prescription pattern of benzodiazepines in hospitalized psychiatric patients-A retrospective case-control investigation.
Keck, ME, Nicolussi, S, Spura, K, Blohm, C, Zahner, C, Drewe, J
Phytotherapy research : PTR. 2020;(6):1436-1445
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Stress is an increasing problem that can result in various psychiatric and somatoform symptoms. Among others, benzodiazepines and valerian preparations are used to treat stress symptoms. The aim of this study was to investigate whether the prescription of a fixed herbal extract combination of valerian, lemon balm, passionflower, and butterbur (Ze 185) changes the prescription pattern of benzodiazepines in hospitalized psychiatric patients. In a retrospective case-control study, anonymized medical record data from 3,252 psychiatric in-house patients were analysed over a 3.5-year period. Cases (n = 1,548) with a prescription of Ze 185 and controls (n = 1,704) were matched by age, gender, hospitalization interval, and main International Classification of Diseases, Version 10 F-diagnoses. The primary objective was to investigate the effect of Ze 185 on the prescription pattern of benzodiazepines. Secondary objectives investigated the prescriptions of concomitant drugs and effectiveness of the hospital stay. Distribution of drug classes was analysed using the WHO's anatomic-therapeutic-chemical code. Data showed that both treatment modalities had a comparable clinical effectiveness but with significantly less prescriptions of benzodiazepines in the Ze 185 group (p = .006). This is of clinical importance because suitable alternatives to benzodiazepines are desirable. To obtain more support for this hypothesis, a dedicated randomized, controlled clinical trial monitoring drug safety is required.
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First-Phase Insulin and Amylin after Bariatric Surgery: A Prospective Randomized Trial on Patients with Insulin Resistance or Diabetes after Gastric Bypass or Sleeve Gastrectomy.
Nussbaumer, R, Meyer-Gerspach, AC, Peterli, R, Peters, T, Beglinger, C, Chiappetta, S, Drewe, J, Wölnerhanssen, B
Obesity facts. 2020;(6):584-595
Abstract
BACKGROUND Most patients with severe obesity show glucose intolerance. Early after sleeve gastrectomy (LSG) or gastric bypass (LRYGB), a marked amelioration in glycemic control occurs. The underlying mechanism is not yet clear. OBJECTIVE To determine whether the improvement in glycemic control on the level of endocrine pancreatic function is due to an increased first-phase insulin secretion comparing LRYGB to LSG. SETTING University of Basel Hospital and St. Clara Research Ltd., Basel, Switzerland. METHODS Sixteen morbidly obese patients with severe obesity and different degrees of insulin resistance were randomized to LSG or LRYGB, and islet cell functions were tested by intravenous glucose and intravenous arginine administration before and 4 weeks after surgery. RESULTS Fasting insulin and glucose levels and homeostasis model assessment insulin resistance were significantly lower in both groups after surgery compared to baseline, while no change was seen in fasting C-peptide, amylin, and glucagon. After intravenous glucose stimulation, no statistically significant pre- to postoperative change in area under the curve (AUC 0-60 min) was seen for insulin, glucagon, amylin, and C-peptide. No statistically significant pre- to postoperative change in incremental AUC for first-phase insulin release (AUC 0-10 min), second-phase insulin secretion (AUC 10-60 min), and insulin/glucose ratio could be shown in either group. Arginine-stimulated insulin and glucagon release showed no pre- to postoperative change. CONCLUSION Intravenous glucose and arginine administrations show no pre- to postoperative changes of insulin release, amylin, glucagon, or C-peptide concentrations, and no differences between LRYGB and LSG were found. The postoperative improvement in glycemic control is not caused by changes in endocrine pancreatic hormone secretion.
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Effects of a fixed herbal drug combination (Ze 185) to an experimental acute stress setting in healthy men - An explorative randomized placebo-controlled double-blind study.
Meier, S, Haschke, M, Zahner, C, Kruttschnitt, E, Drewe, J, Liakoni, E, Hammann, F, Gaab, J
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2018;:85-92
Abstract
BACKGROUND Considering the negative effects of stress on health, there is a growing interest in stress-reducing interventions. The present study examines the effects of a fixed combination of valerian, passion flower, lemon balm, and butterbur extracts (Ze 185) on biological and affective responses to a standardized psychosocial stress paradigm. PURPOSE The aim of the present study was to investigate the efficacy of Ze 185 on cortisol and anxiety stress responses to acute psychosocial stress in healthy subjects. STUDY DESIGN This study was a randomized, placebo-controlled, double blind study with 3 parallel groups. METHODS 72 healthy male participants were randomized to 3 groups (Ze 185, placebo or no treatment) during 4 days prior to a standardized psychosocial stress paradigm. Principle outcomes were salivary cortisol and self-reported anxiety responses to stress assessed at the fourth day. RESULTS The stress paradigm induced significant and large cortisol and self-reported anxiety responses. Groups did not differ significantly in their salivary cortisol response to stress, but participants in the Ze 185 condition showed significantly attenuated responses in self-reported anxiety in comparison to placebo (F(3, 41) = 3.33, p = 0.03) and no treatment (F(3, 43) = 2.77, p = 0.05). CONCLUSION The results show that Ze 185 significantly attenuated the subjective emotional stress response during an acute stress situation, without affecting biological stress responses. Given that a circumscribed biological stress response is to be considered as an adaptive mechanism, Ze 185 reduces self-reported anxiety response to stress without affecting assumingly adaptive biological stress responses.
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Green tea effects on cognition, mood and human brain function: A systematic review.
Mancini, E, Beglinger, C, Drewe, J, Zanchi, D, Lang, UE, Borgwardt, S
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2017;:26-37
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BACKGROUND Green tea (Camellia sinensis) is a beverage consumed for thousands of years. Numerous claims about the benefits of its consumption were stated and investigated. As green tea is experiencing a surge in popularity in Western culture and as millions of people all over the world drink it every day, it is relevant to understand its effects on the human brain. PURPOSE To assess the current state of knowledge in the literature regarding the effects of green tea or green tea extracts, l-theanine and epigallocatechin gallate both components of green tea-on general neuropsychology, on the sub-category cognition and on brain functions in humans. METHODS We systematically searched on PubMed database and selected studies by predefined eligibility criteria. We then assessed their quality and extracted data. We structured our effort according to the PRISMA statement. OUTCOME We reviewed and assessed 21 studies, 4 of which were randomised controlled trials, 12 cross-over studies (both assessed with an adapted version of the DELPHI-list), 4 were cross-sectional studies and one was a cohort study (both assessed with an adapted version of the Newcastle-Ottawa assessment scale). The average study quality as appraised by means of the DELPHI-list was good (8.06/9); the studies evaluated with the Newcastle-Ottawa-scale were also good (6.7/9). CONCLUSIONS The reviewed studies presented evidence that green tea influences psychopathological symptoms (e.g. reduction of anxiety), cognition (e.g. benefits in memory and attention) and brain function (e.g. activation of working memory seen in functional MRI). The effects of green tea cannot be attributed to a single constituent of the beverage. This is exemplified in the finding that beneficial green tea effects on cognition are observed under the combined influence of both caffeine and l-theanine, whereas separate administration of either substance was found to have a lesser impact.
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The impact of gut hormones on the neural circuit of appetite and satiety: A systematic review.
Zanchi, D, Depoorter, A, Egloff, L, Haller, S, Mählmann, L, Lang, UE, Drewe, J, Beglinger, C, Schmidt, A, Borgwardt, S
Neuroscience and biobehavioral reviews. 2017;:457-475
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The brain-gut-axis is an interdependent system affecting neural functions and controlling our eating behaviour. In recent decades, neuroimaging techniques have facilitated its investigation. We systematically looked into functional and neurochemical brain imaging studies investigating how key molecules such as ghrelin, glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), cholecystokinin (CCK), leptin, glucose and insulin influence the function of brain regions regulating appetite and satiety. Of the 349 studies published before July 2016 identified in the database search, 40 were included (27 on healthy and 13 on obese subjects). Our systematic review suggests that the plasma level of ghrelin, the gut hormone promoting appetite, is positively correlated with activation in the pre-frontal cortex (PFC), amygdala and insula and negatively correlated with activation in subcortical areas such as the hypothalamus. In contrast, the plasma levels of glucose, insulin, leptin, PYY, GLP-1 affect the same brain regions conversely. Our study integrates previous investigations of the gut-brain matrix during food-intake and homeostatic regulation and may be of use for future meta-analyses of brain-gut interactions.