scholarly journals High dose saccharin supplementation does not induce gut microbiota dysbiosis or glucose intolerance in healthy humans and mice

2020 ◽  
Author(s):  
Joan Serrano ◽  
Kathleen R Smith ◽  
Audra L Crouch ◽  
Vandana Sharma ◽  
Fanchao Yi ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Gut Microbiota ◽  
Glucose Intolerance ◽  
Ex Vivo ◽  
Daily Intake ◽  
Sweet Taste ◽  
High Dose ◽  
Double Blind ◽  
Genetic Ablation ◽  
Healthy Humans

Abstract Background : Non-caloric artificial sweeteners (NCAS) are widely used as a substitute for dietary sugars to control body weight or glycemia. Paradoxically, saccharin and other NCAS have been reported to induce glucose intolerance in mice fed a high-fat diet and in a subset of humans by directly inducing unfavorable changes in gut microbiota. These findings have raised concerns about NCAS and called into question their broad use. Whether these results can be generalized to healthy populations consuming conventional diets is unknown. It is also unclear how different NCAS, that do not share a common chemical structure, can produce identical direct effects on gut microbiota. A common feature of all NCAS is their strong affinity for sweet taste receptors (STRs) which are expressed in the intestine. However, their role in mediating NCAS-induced effects has not been addressed. Results : We conducted a double-blind, placebo-controlled, parallel arm study exploring the effects of saccharin on gut microbiota and glucose tolerance in healthy men and women. Participants were randomized to placebo, saccharin, lactisole (STR inhibitor), or saccharin with lactisole administered in capsules twice daily to achieve the maximum acceptable daily intake for two weeks. In parallel, we performed a ten-week study administering high-dose saccharin in the drinking water of chow-fed mice with genetic ablation of STRs (T1R2-KO) and wild-type (WT) littermate controls. In humans and mice alike, none of the interventions affected glucose or hormonal responses to a glucose tolerance test, nor ex vivo glucose absorption in mice. Similarly, saccharin supplementation did not alter microbial diversity or abundance at any taxonomic level in humans or mice. No treatment effects were also noted in readouts of microbial activity such as fecal metabolites or short chain fatty acids (SCFA). However, compared to WT, T1R2-KO mice were protected from age-dependent increases in fecal SCFA and the development of glucose intolerance.

scholarly journals High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Joan Serrano ◽  
Kathleen R. Smith ◽  
Audra L. Crouch ◽  
Vandana Sharma ◽  
Fanchao Yi ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Gut Microbiota ◽  
Glucose Intolerance ◽  
Trial Registration ◽  
Metabolic Effects ◽  
Common Mechanism ◽  
Oral Glucose ◽  
High Dose ◽  
Genetic Ablation ◽  
Healthy Humans

Abstract Background Non-caloric artificial sweeteners (NCAS) are widely used as a substitute for dietary sugars to control body weight or glycemia. Paradoxically, some interventional studies in humans and rodents have shown unfavorable changes in glucose homeostasis in response to NCAS consumption. The causative mechanisms are largely unknown, but adverse changes in gut microbiota have been proposed to mediate these effects. These findings have raised concerns about NCAS safety and called into question their broad use, but further physiological and dietary considerations must be first addressed before these results are generalized. We also reasoned that, since NCAS are bona fide ligands for sweet taste receptors (STRs) expressed in the intestine, some metabolic effects associated with NCAS use could be attributed to a common mechanism involving the host. Results We conducted a double-blind, placebo-controlled, parallel arm study exploring the effects of pure saccharin compound on gut microbiota and glucose tolerance in healthy men and women. Participants were randomized to placebo, saccharin, lactisole (STR inhibitor), or saccharin with lactisole administered in capsules twice daily to achieve the maximum acceptable daily intake for 2 weeks. In parallel, we performed a 10-week study administering pure saccharin at a high dose in the drinking water of chow-fed mice with genetic ablation of STRs (T1R2-KO) and wild-type (WT) littermate controls. In humans and mice, none of the interventions affected glucose or hormonal responses to an oral glucose tolerance test (OGTT) or glucose absorption in mice. Similarly, pure saccharin supplementation did not alter microbial diversity or composition at any taxonomic level in humans and mice alike. No treatment effects were also noted in readouts of microbial activity such as fecal metabolites or short-chain fatty acids (SCFA). However, compared to WT, T1R2-KO mice were protected from age-dependent increases in fecal SCFA and the development of glucose intolerance. Conclusions Short-term saccharin consumption at maximum acceptable levels is not sufficient to alter gut microbiota or induce glucose intolerance in apparently healthy humans and mice. Trial registration Trial registration number NCT03032640, registered on January 26, 2017.

scholarly journals A Single Administration of AZP-3601, a Novel, Long-Acting PTH Analog, Induces a Significant and Sustained Calcemic Response: Preliminary Data From a Randomized, Double-Blind, Placebo-Controlled Phase 1 Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A254-A254
Author(s):  
Soraya Allas ◽  
Michel Ovize ◽  
Michael D Culler ◽  
Clarisse Geraul ◽  
Jeroen van de Wetering ◽  
...  
Keyword(s):  
Serum Calcium ◽  
Clinical Symptoms ◽  
Phase 1 ◽  
High Dose ◽  
Single Administration ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Healthy Humans ◽  
Dose Dependent

Abstract Hypoparathyroidism is a rare disease characterized by a deficiency in parathyroid hormone (PTH) that results in hypocalcemia and hyperphosphatemia. Current treatment approaches, including high dose oral calcium and active vitamin D, as well as recombinant human PTH (1–84), do not provide adequate or consistent control of either serum calcium or clinical symptoms over a full 24-hour period. AZP-3601 is a novel 36 amino-acid PTH analog that has been designed to potently bind to the R0 conformation of the PTH1 receptor, which results in prolonged signaling responses in vitro and prolonged calcemic responses in animals despite having a short circulating half-life. A Phase 1 double-blind, placebo-controlled, single and multiple ascending dose study is being conducted to evaluate the safety, tolerability and pharmacodynamics of AZP-3601 in healthy adults. Here we report data from the first cohorts of the single ascending dose portion of the study. Sequential cohorts of 4 (cohort 1) to 8 (cohort 2 to 4) healthy male subjects aged 18–60 years, with a body mass index of 19–28 kg/m2, were assigned to receive 5, 10, 20 or 40μg of AZP-3601 or placebo at a ratio of 3:1. The study drug was administered in the morning by subcutaneous injection in the abdominal wall and was well tolerated with no remarkable adverse events. As compared with placebo controls, AZP-3601 treatment produced a clear, dose-dependent increase in mean albumin-adjusted serum calcium values from baseline. The normal physiological diurnal variation of albumin-adjusted serum calcium was gradually attenuated with 5 and 10μg AZP-3601, and was completely eliminated with 20μg. With the dose of 40μg AZP-3601, mean albumin-adjusted serum calcium values were significantly increased but stayed within normal laboratory range and remained elevated through at least 24 hours post-administration. We observed a dose-dependent decrease in mean endogenous serum PTH that was significantly correlated with the concomitant increase in mean serum calcium. These data provide initial evidence of the pharmacodynamic effect of AZP-3601 in healthy humans characterized by a sustained calcemic response for at least 24 hours following a single administration.

scholarly journals Effect of stevia on the gut microbiota and glucose tolerance in a murine model of diet-induced obesity

2020 ◽  
Vol 96 (6) ◽  
Author(s):  
Sarah L Becker ◽  
Edna Chiang ◽  
Anna Plantinga ◽  
Hannah V Carey ◽  
Garret Suen ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Gut Microbiota ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
High Fat ◽  
Low Fat ◽  
Treatment Groups ◽  
Low Fat Diet ◽  
Taxonomic Groups ◽  
Induced Changes

ABSTRACT Artificial sweeteners have been shown to induce glucose intolerance by altering the gut microbiota; however, little is known about the effect of stevia. Here, we investigate whether stevia supplementation induces glucose intolerance by altering the gut microbiota in mice, hypothesizing that stevia would correct high fat diet-induced glucose intolerance and alter the gut microbiota. Mice were split into four treatment groups: low fat, high fat, high fat + saccharin and high fat + stevia. After 10 weeks of treatment, mice consuming a high fat diet (60% kcal from fat) developed glucose intolerance and gained more weight than mice consuming a low fat diet. Stevia supplementation did not impact body weight or glucose intolerance. Differences in species richness and relative abundances of several phyla were observed in low fat groups compared to high fat, stevia and saccharin. We identified two operational taxonomic groups that contributed to differences in beta-diversity between the stevia and saccharin groups: Lactococcus and Akkermansia in females and Lactococcus in males. Our results demonstrate that stevia does not rescue high fat diet-induced changes in glucose tolerance or the microbiota, and that stevia results in similar alterations to the gut microbiota as saccharin when administered in concordance with a high fat diet.

scholarly journals Effect of Lactobacillus plantarum TWK10 on Exercise Physiological Adaptation, Performance, and Body Composition in Healthy Humans

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2836 ◽  
Author(s):  
Wen-Ching Huang ◽  
Mon-Chien Lee ◽  
Chia-Chia Lee ◽  
Ker-Sin Ng ◽  
Yi-Ju Hsu ◽  
...  
Keyword(s):  
Body Composition ◽  
Lactobacillus Plantarum ◽  
Athletic Training ◽  
Exercise Performance ◽  
Exercise Physiology ◽  
Physiological Adaptation ◽  
High Dose ◽  
Dependent Manner ◽  
Double Blind ◽  
Healthy Humans

Probiotics have been rapidly developed for health promotion, but clinical validation of the effects on exercise physiology has been limited. In a previous study, Lactobacillus plantarum TWK10 (TWK10), isolated from Taiwanese pickled cabbage as a probiotic, was demonstrated to improve exercise performance in an animal model. Thus, in the current study, we attempted to further validate the physiological function and benefits through clinical trials for the purpose of translational research. The study was designed as a double-blind placebo-controlled experiment. A total of 54 healthy participants (27 men and 27 women) aged 20–30 years without professional athletic training were enrolled and randomly allocated to the placebo, low (3 × 1010 colony forming units (CFU)), and high dose (9 × 1010 CFU) TWK10 administration groups (n = 18 per group, with equal sexes). The functional and physiological assessments were conducted by exhaustive treadmill exercise measurements (85% VO2max), and related biochemical indices were measured before and after six weeks of administration. Fatigue-associated indices, including lactic acid, blood ammonia, blood glucose, and creatinine kinase, were continuously monitored during 30 min of exercise and a 90 min rest period using fixed intensity exercise challenges (60% VO2max) to understand the physiological adaptation. The systemic inflammation and body compositions were also acquired and analyzed during the experimental process. The results showed that TWK10 significantly elevated the exercise performance in a dose-dependent manner and improved the fatigue-associated features correlated with better physiological adaptation. The change in body composition shifted in the healthy direction for TWK10 administration groups, especially for the high TWK10 dose group, which showed that body fat significantly decreased and muscle mass significantly increased. Taken together, our results suggest that TWK10 has the potential to be an ergogenic aid to improve aerobic endurance performance via physiological adaptation effects.

scholarly journals High-dose thiamine supplementation improves glucose tolerance in hyperglycemic individuals: a randomized, double-blind cross-over trial

2013 ◽  
Vol 52 (7) ◽  
pp. 1821-1824 ◽  
Author(s):  
F. Alaei Shahmiri ◽  
M. J. Soares ◽  
Y. Zhao ◽  
J. Sherriff
Keyword(s):  
Glucose Tolerance ◽  
High Dose ◽  
Double Blind

scholarly journals Daily intake of Citrus jabara fruit peel powder (Japanese Patent No. 5,323,127) improves allergy-like symptoms: A randomized double-blind parallel-group comparative study

2021 ◽  
Vol 5 (2) ◽  
pp. 21
Author(s):  
Seisho Azuma ◽  
Yoshinobu Murakami ◽  
Masahiko Taniguchi ◽  
Kimiye Baba ◽  
Toru Mima ◽  
...  
Keyword(s):  
Daily Intake ◽  
Safety Evaluation ◽  
Citrus Fruit ◽  
Oral Intake ◽  
High Dose ◽  
Life Questionnaire ◽  
Fruit Peel ◽  
Double Blind ◽  
Japanese Patent ◽  
Parallel Group

Citrus jabara (CJ) is a rare citrus fruit that used to grow naturally only in the southern part of the Kii Peninsula in Japan. Human intervention studies with oral intake of CJ fruit have shown its anti-allergic effects, but the testing method was a pre-post comparison study. In this study, we conducted a randomized, double-blind, parallel-group interventional study to evaluate the volume-dependent effects of oral intake of CJ fruit peel powder (Japanese Patent No. 5,323,127) on nasal and eye allergy-like symptoms. Ninety healthy adults were allocated to three groups and given test foods containing 1,000, 500, and 0 mg of CJ peel powder, with one packet per day for 4 weeks. After excluding those who dropped out or deviated from the study protocol, 73 were included in the efficacy analysis and 86 in the safety analysis. The high-dose group (1,000 mg/day) was significantly lower than the placebo group in the scores of “nasal and eye symptoms” at week 4, and “blocked nose” at weeks 2 and 4 in the evaluation of question I of Japanese Rhino-conjunctivitis Quality of Life Questionnaire (JRQLQ No. 1). The changes in scores (difference from the pre-observation period) on the Nasal and Eye Symptom Questionnaire showed a dose-dependent reduction in rhinorrhea. In the safety evaluation, there were no significant differences in examinations of physiology, hematology, and blood biochemistry between the groups, and no adverse events attributable to the test foods were observed. These results suggest that intake of CJ peel powder can alleviate allergy-like symptoms.

scholarly journals Universal adaptive evolution strategy of probiotic Lactobacillus plantarum to gut selection pressure from humans, mice and zebrafish

2021 ◽  
Author(s):  
Shi Huang ◽  
Shuaiming Jiang ◽  
Dongxue Huo ◽  
Celeste Allaband ◽  
Mehrbod Estaki ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Lactobacillus Plantarum ◽  
Ex Vivo ◽  
Acid Tolerance ◽  
Adaptive Strategy ◽  
Adaptation Strategy ◽  
Carbohydrate Utilization ◽  
Healthy Humans ◽  
Probiotic Lactobacillus

Abstract Improving the probiotic engraftment in humans requires a thorough understanding of in vivo gut-adaptive strategy of probiotics in diverse contexts. Here, we exposed the probiotic Lactobacillus plantarum HNU082 (Lp082) to gut microbiota of healthy humans, mice, and zebrafish for four weeks. Independent of host choice, Lp082 established and adapted the gut by acquiring highly consistent single-nucleotide mutations, which modulated carbohydrate utilization, and acid tolerance, and significantly promoted its in vivo competitive fitness. In turn, resident gut microbial strains, especially competing strains with Lp082 (e.g. Bacteroides spp. and Bifidobacterium spp.), actively respond to Lp082 engraftment by accumulating 10-70 folds more evolutionary changes than usual. Human gut microbiota exhibited a higher ecological and genetic stability than that of mice. Collectively, the highly convergent adaptation strategy of Lp082 across host environments lay the foundation for leveraging the animal model for ex vivo engineering of probiotics for better engraftment outcomes in humans.

Effects of the Tibetan herbal preparation PADMA 28 on blood lipids and lipid oxidisability in subjects with mild hypercholesterolaemia

VASA ◽  
2005 ◽  
Vol 34 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Brunner-La Rocca ◽  
Schindler ◽  
Schlumpf ◽  
Saller ◽  
Suter
Keyword(s):  
Endothelial Dysfunction ◽  
Blood Lipids ◽  
Ex Vivo ◽  
Hdl Cholesterol ◽  
Blood Lipid ◽  
Tibetan Medicine ◽  
Double Blind ◽  
Intraarterial Infusion ◽  
Padma 28

Background: Previous studies showed an anti-atherosclerotic effect of PADMA 28, an herbal formula based on Tibetan medicine. As the mechanisms of action are not fully understood, we investigated whether PADMA 28 may lower blood lipids and lipid oxidisability, and affect early endothelial dysfunction. Patients and methods: Sixty otherwise healthy subjects with total cholesterol ≥5.2 mmol/l and < 8.0 mmol/l were randomly assigned to placebo or PADMA 28, 3 x 2 capsules daily, for 4 weeks (double-blind). Blood lipids (total, LDL-, and HDL-cholesterol, triglycerides, Apo-lipoprotein A1 and B) and ex vivo lipid oxidisability were measured before and after treatment. In a subset of 24 subjects, endothelial function was assessed using venous occlusion plethysmography with intraarterial infusion of acetylcholine. Isolated LDL and plasma both untreated and pre-treated with PADMA 28 extract were oxidised by the radical generator AAPH. Conjugated diene formation was measured at 245 nm. Results: Blood lipids did not change during the study in both groups. In contrast to previous reports in mild hypercholesterolaemia, no endothelial dysfunction was seen and, consequently, was not influenced by therapy. Ex vivo blood lipid oxidisability was significantly reduced with PADMA 28 (area under curve: 5.29 ± 1.62 to 4.99 ± 1.46, p = 0.01), and remained unchanged in the placebo group (5.33 ± 1.88 to 5.18 ± 1.78, p > 0.1). This effect persisted one week after cessation of medication. In vitro experiments confirmed the prevention of lipid peroxidation in the presence of PADMA 28 extracts. Persistent protection was also seen for LDL isolated from PADMA 28-pretreated blood after being subjected to rigorous purification. Conclusions: This study suggests that the inhibition of blood lipid oxidisability by PADMA 28 may play a role in its anti-atherosclerotic effect.

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