Clinical Quickies (March-June 2023)

1. Ashwagandha is not Only an Adaptogen, but Possibly an Enhancer for Sexual Function in Healthy Females
2. Exercise-Based Intervention Reduces Arrhythmia Recurrence and Symptom Severity in A. Fib Patients
3. People with a Higher BMI may Have a Blunted Response to Vitamin D Supplementation
4. Pine Bark Extract with Gotu Kola Extract Could Reduce Central Cardiovascular Calcification in Twelve Months
5. Vitamin D Supplementation can Likely Reduce the Risk of Progressing from Pre-diabetes to Diabetes
6.Are Mixed Tocopherols an Overlooked Remedy for Helping Patients Suffering from Chronic Insomnia?
7. Moderate to Vigorous Physical Activities may Reduce the Risk of Progressing to Type 1 Diabetes in Children with Islet Autoantibodies
8. Vitamin D3 Supplementation Improves the Effectiveness of ED Medication, Especially in Patients with Low Vit D Levels
9. Low-Carbohydrate Diet may Cause Dysfunction in Glucose Homeostasis in Healthy Normal Weight Individuals
10. Healthy Individuals Become Less Glucose Tolerant After 2 Weeks of Ingesting Artificial Sweeteners, which Adversely Affect the Microbiome
11. Sucralose-6-Acetate Appears to Damage Rodent DNA and Induces Leaky Gut, Raising Concerns for Sucralose as a Safe Artificial Sweetener
12. Gel Based on Sage Extract Appears to Speed up Healing Time of Aphthous Ulcers

1. Ashwagandha is not Only an Adaptogen, but Possibly an Enhancer for Sexual Function in Healthy Females

BACKGROUND: Poor sexual function is a widespread problem affecting about 40% of women and this may worsen their quality of life. Ashwagandha (Withania somnifera) an adaptogenic herb has been reported to improve sexual satisfaction, sleep, and quality of life in women. 

OBJECTIVE: The purpose of the study was to evaluate the efficacy and safety of standardized Ashwagandha root extract in improving sexual function in healthy females. METHODS: In this prospective, randomized, placebo-controlled study, 80 women between 18 and 50 years of age without any hormonal disturbances and having hypoactive sexual desire disorder (HSDD) with a Female Sexual Function Index (FSFI) score <26, or Female Sexual Distress Scale (FSDS) score >11 were randomized to receive either capsule containing standardized Ashwagandha root extract 300mg twice daily (n=40), or identical placebo (n=40) for eight weeks. Sexual function was assessed using FSFI, FSDS, and Satisfying Sexual Encounters (SSEs). Assessments were done at baseline, four weeks, and eight weeks. Quality of life (QoL) was assessed using the general health questionnaire (GHQ-28) scale, and safety was assessed using clinical signs and symptoms. Repeat measures analysis of variance (ANOVA) was used for the assessment of treatment effect at different time periods. Nominal data were analyzed for differences using Fischer’s Chi-square test. 

RESULTS: There was statistically significant improvement (p<0.0001) in FSFI scores with Ashwagandha [14.20 (0.98) at baseline to 22.62 (2.06) at week 8] as compared to placebo [14.17 (0.71) at baseline to 19.25 (2.23) at eight weeks], and this improvement was observed in all sub-scales (desire, arousal, lubrication, orgasm, sexual satisfaction, and pain) of the FSFI scale. There was a greater improvement (p<0.0001) in FSDS scores with AG as compared to placebo. Although not statistically significant (p, 0.078), there was a greater reduction (improvement) in GHQ-28 scores at eight weeks with Ashwagandha as compared to placebo, and this trend was observed for all domains of GHQ-28 (global, physical, psychological, and social function). More women with Ashwagandha had improvement in SSEs at week 4 (p, 0.017) and week 8 (p, 0.002) as compared to placebo. Adverse events were comparable in the two groups. Two women reported nausea and one reported drowsiness with AG, whereas two reported nausea, one reported drowsiness and one reported nausea with drowsiness in the placebo group.

CONCLUSIONS: Oral administration of Ashwagandha 300mg twice daily administered for eight weeks improves the female sexual health in otherwise healthy women who do not have any hormonal disturbances. Ashwagandha is a known adaptogen, maintains general well-being and improves vitality.

Ajgoankar A, et al. Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract for Improvement of Sexual Health in Healthy Women: A Prospective, Randomized, Placebo-Controlled Study. Cureus. 2022 Oct 28;14(10):e30787.  doi: 10.7759/cureus.30787. eCollection 2022 Oct.

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2. Exercise-Based Intervention Reduces Arrhythmia Recurrence and Symptom Severity in A. Fib Patients

BACKGROUND: There are limited data on the effect of exercise interventions on atrial fibrillation (AF) recurrence and symptoms.

OBJECTIVES: The aim of this study was to determine the efficacy of an exercise and physical activity intervention on AF burden and symptoms among patients with symptomatic AF.

METHODS: This prospective, randomized controlled trial included 120 patients with paroxysmal or persistent, symptomatic AF, randomized 1:1 to receive an exercise intervention, combining home and supervised aerobic exercise over 6 months, or to receive usual care. The coprimary outcomes were: 1) AF recurrence, off antiarrhythmic medications and without catheter ablation; and 2) symptom severity assessed by using a validated questionnaire.

RESULTS: By 12 months, freedom from AF was achieved in 24 (40%) of 60 patients in the exercise group and 12 (20%) of 60 patients in the control group (HR: 0.50: 95% CI: 0.33 to 0.78). At 6 months, AF symptom severity was lower in the exercise group compared with the control group (mean difference -2.3; 95% CI: -4.3 to -0.2; P = 0.033). This difference persisted at 12 months (-2.3; 95% CI: -4.5 to -0.1; P = 0.041). Total symptom burden was lower at 6 months in the exercise group but not at 12 months. Peak oxygen consumption was increased in the exercise group at both 6 and 12 months. There were no between-group differences in cardiac structure or function, body mass index, or blood pressure.

CONCLUSIONS: Participation in an exercise-based intervention over 6 months reduced arrhythmia recurrence and improved symptom severity among patients with AF. (A Lifestyle-based, PhysiCal AcTIVity IntErvention for Patients With Symptomatic Atrial Fibrillation [the ACTIVE-AF Study]; ACTRN12615000734561).

Elliott AD, et al. An Exercise and Physical Activity Program in Patients With Atrial Fibrillation: The ACTIVE-AF Randomized Controlled Trial. JACC Clin Electrophysiol. 2023 Apr;9(4):455-465. doi: 10.1016/j.jacep.2022.12.002. Epub 2023 Jan 18.

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3. People with a Higher BMI may Have a Blunted Response to Vitamin D Supplementation

IMPORTANCE: In the Vitamin D and Omega-3 Trial (VITAL), the effects of randomized vitamin D supplementation (cholecalciferol), 2000 IU/d, reduced the risk of several health outcomes among participants with normal, but not elevated, body weights. It was unclear whether weight had any association with the outcomes of the supplementation.

OBJECTIVE: To investigate whether baseline body mass index (BMI) modifies vitamin D metabolism and response to supplementation.

DESIGN, SETTING, AND PARTICIPANTS: VITAL is a completed randomized, double-blind, placebo-controlled trial for the primary prevention of cancer and cardiovascular disease. In the present cohort study, an analysis was conducted in a subset of VITAL participants who provided a blood sample at baseline and a subset with a repeated sample at 2 years’ follow-up. VITAL was conducted from July 1, 2010, to November 10, 2018; data analysis for the present study was conducted from August 1, 2021, to November 9, 2021.

INTERVENTIONS: Treatment outcomes of vitamin D, 2000 IU/d, supplementation vs placebo associated with clinical and novel vitamin D-related biomarkers by BMI category adjusted for other factors associated with vitamin D status.

MAIN OUTCOMES AND MEASURES: Multivariable-adjusted means (SE) or 95% CIs of vitamin D-related serum biomarkers at baseline and follow-up: total 25-hydroxyvitamin D (25-OHD), 25-OHD3, free vitamin D (FVD), bioavailable vitamin D (BioD), vitamin D-binding protein (VDBP), albumin, parathyroid hormone (PTH), and calcium, and log-transformed as needed.

RESULTS: A total of 16 515 participants (mean [SD] age, 67.7 [7.0] years; 8371 women [50.7%]; 12420 non-Hispanic White [76.9%]) were analyzed at baseline, including 2742 with a follow-up blood sample. Before randomization, serum total 25-OHD levels were incrementally lower at higher BMI categories (adjusted mean [SE]: underweight, 32.3 [0.7] ng/mL; normal weight, 32.3 [0.1] ng/mL; overweight, 30.5 [0.1] ng/mL; obesity class I, 29.0 [0.2] ng/mL; and obesity class II, 28.0 [0.2] ng/mL; P < .001 for linear trend).

Similarly, baseline 25-OHD3, FVD, BioD, VDBP, albumin, and calcium levels were lower with higher BMI, while PTH level was higher (all P < .001 for linear trend). Compared with placebo, randomization to vitamin D supplementation was associated with an increase in total 25-OHD, 25-OHD3, FVD, and BioD levels compared with placebo at 2 years’ follow-up, but increases were significantly lower at higher BMI categories (all treatment effect interactions P < .001). Supplementation did not substantially change VDBP, albumin, PTH, or calcium levels.

CONCLUSIONS AND RELEVANCE: In this randomized cohort study, vitamin D supplementation increased serum vitamin D-related biomarkers, with a blunted response observed for participants with overweight or obesity at baseline. These longitudinal findings suggest that BMI may be associated with modified response to vitamin D supplementation and may in part explain the observed diminished outcomes of supplementation for various health outcomes among individuals with higher BMI.

Tobias DK, et al. Association of Body Weight With Response to Vitamin D Supplementation and Metabolism. JAMA Netw Open. 2023 Jan 3;6(1):e2250681. doi: 10.1001/jamanetworkopen. 2022.50681.

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4. Pine Bark Extract with Gotu Kola Extract Could Reduce Central Cardiovascular Calcification in Twelve Months

BACKGROUND: This ‘concept’ registry study evaluated the efficacy of Pycnogenol® and the combination Pycnogenol® and Centella Asiatica (Centellicum®) in controlling over 12 months the increasing number of arterial/cardiac calcifications in subjects with asymptomatic atherosclerosis.

METHODS: The study included 3 groups of 30 males with asymptomatic coronary calcifications. Group one was followed with standard management (SM); group 2 used SM and Pycnogenol® (150 mg/day); group 3 used the combination Pycnogenol® (150 mg/day) + Centellicum® (450 mg/day). All subjects took cardioaspirin (Bayer, 100 mg/day).

RESULTS: No dropouts, no clinical events were observed in 12 months. The 3 groups had comparable demographic and medical characteristics at baseline. No tolerability problems and no side effects from supplementation were reported. After 12 months, oxidative stress was significantly decreased (P<0.05) in both groups taking Pycnogenol®. The evaluation of the number of calcifications >1 mm indicated a trend in controls using SM towards a progressive increase in calcifications. At 12 months the decrease in the number of calcifications with the combined supplements (Pycnogenol® and Centellicum®) (group 3) was -9.952% and thus significantly better that in the other two groups (P<0.05). Pycnogenol® alone was more effective than SM alone in controlling the variation in calcifications (P<0.05). Considering a 34.88% increase in SM subjects, the total absolute difference between SM (34.8%) and the decrease observed in group 3 (-9.95%) was 44.75% (P<0.02). This indicates that supplementation with the combined supplements blocks the increase in calcified areas and, possibly, in time may decrease the number of calcified spots.

CONCLUSIONS: This study shows that there is a significant activity of the complex Pycnogenol®+ Centellicum® in reducing the progressive diffusion of central cardiovascular calcifications-associated with advanced plaques – in a relatively short period of time. Longer studies – focusing also on events – may better evaluate the efficacy of these standardized supplements combination on the evolution of atherosclerosis.

Hu S, et al. Central cardiovascular calcifications: supplementation with Pycnogenol® and Centellicum®: variations over 12 months. Minerva Cardioangiol. 2020 Feb;68(1):22-26. doi: 10.23736/S0026-4725.19.05052-7. Epub 2019 Oct 15.

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5. Vitamin D Supplementation can Likely Reduce the Risk of Progressing from Pre-diabetes to Diabetes

BACKGROUND: The role of vitamin D in people who are at risk for type 2 diabetes remains unclear.

PURPOSE: To evaluate whether administration of vitamin D decreases risk for diabetes among people with prediabetes.

DATA SOURCES: PubMed, Embase, and ClinicalTrials.gov from database inception through 9 December 2022.

STUDY SELECTION: Eligible trials that were specifically designed and conducted to test the effects of oral vitamin D versus placebo on new-onset diabetes in adults with prediabetes.

DATA EXTRACTION: The primary outcome was time to event for new-onset diabetes. Secondary outcomes were regression to normal glucose regulation and adverse events. Prespecified analyses (both unadjusted and adjusted for key baseline variables) were conducted according to the intention-to-treat principle.

DATA SYNTHESIS: Three randomized trials were included, which tested cholecalciferol, 20 000 IU (500 mcg) weekly; cholecalciferol, 4000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, versus matching placebos. Trials were at low risk of bias. Vitamin D reduced risk for diabetes by 15% (hazard ratio, 0.85 [95% CI, 0.75 to 0.96]) in adjusted analyses, with a 3-year absolute risk reduction of 3.3% (CI, 0.6% to 6.0%). The effect of vitamin D did not differ in prespecified subgroups. Among participants assigned to the vitamin D group who maintained an intratrial mean serum 25-hydroxyvitamin D level of at least 125 nmol/L (≥50 ng/mL) compared with 50 to 74 nmol/L (20 to 29 ng/mL) during follow-up, cholecalciferol reduced risk for diabetes by 76% (hazard ratio, 0.24 [CI, 0.16 to 0.36]), with a 3-year absolute risk reduction of 18.1% (CI, 11.7% to 24.6%). Vitamin D increased the likelihood of regression to normal glucose regulation by 30% (rate ratio, 1.30 [CI, 1.16 to 1.46]). There was no evidence of difference in the rate ratios for adverse events (kidney stones: 1.17 [CI, 0.69 to 1.99]; hypercalcemia: 2.34 [CI, 0.83 to 6.66]; hypercalciuria: 1.65 [CI, 0.83 to 3.28]; death: 0.85 [CI, 0.31 to 2.36]).

LIMITATIONS: Studies of people with prediabetes do not apply to the general population. Trials may not have been powered for safety outcomes.

CONCLUSION: In adults with prediabetes, vitamin D was effective in decreasing risk for diabetes.

PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42020163522)

Pittas AG, et al. Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials. Ann Intern Med. 2023 Mar;176(3):355-363. doi: 10.7326/M22-3018. Epub 2023 Feb 7.

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6. Are Mixed Tocopherols an Overlooked Remedy for Helping Patients Suffering from Chronic Insomnia?

ABSTRACT: Chronic insomnia disorder is one of the most common problems in postmenopausal women, exacerbated by underdiagnosis and improper treatment. This double-blinded, randomized, placebo-controlled trial was conducted to evaluate the potential of vitamin E to treat chronic insomnia as an alternative to sedative drugs and hormonal therapy. The study enrolled 160 postmenopausal women with chronic insomnia disorder, divided randomly into two groups. The vitamin E group received 400 units of mixed tocopherol daily, while the placebo group received an identical oral capsule.

The primary outcome of this study was sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI), a self-evaluated and standardized questionnaire. The secondary outcome was the percentage of participants using sedative drugs. There were no significant differences in baseline characteristics between the study groups. However, the median PSQI score at baseline was slightly higher in the vitamin E group compared with the placebo (13 (6, 20) vs. 11 (6, 20); p-value 0.019). After one month of intervention, the PSQI score was significantly lower (indicating better sleep quality) in the vitamin E group compared with the placebo (6 (1, 18) vs. 9 (1, 19); p-value 0.012). Moreover, the improvement score was significantly higher in the vitamin E group compared with the placebo (5 (-6, 14) vs. 1 (-5,13); p-value < 0.001).

In addition, there was a significant reduction in the percentage of patients using sedative drugs in the vitamin E group (15%; p-value 0.009), while this reduction was not statistically significant in the placebo group (7.5%; p-value 0.077). This study demonstrates vitamin E’s potential as an excellent alternative treatment for chronic insomnia disorder that improves sleep quality and reduces sedative drug use.

Thongchumnum W, et al. Effect of Vitamin E Supplementation on Chronic Insomnia Disorder in Postmenopausal Women: A Prospective, Double-Blinded Randomized Controlled Trial. Nutrients. 2023 Feb 27;15(5):1187. doi: 10.3390/nu15051187.

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7. Moderate to Vigorous Physical Activities may Reduce the Risk of Progressing to Type 1 Diabetes in Children with Islet Autoantibodies

OBJECTIVE: This study investigated physical activity and its association with the development of islet autoimmunity and type 1 diabetes in genetically at-risk children aged 5-15 years.

RESEARCH DESIGN AND METHODS: As part of the longitudinal Environmental Determinants of Diabetes in the Young (TEDDY) study, annual assessment of activity using accelerometry was conducted from age 5 years. Time-to-event analyses using Cox proportional hazard models were used to assess the association between time spent in moderate to vigorous physical activity per day and the appearance of one or several autoantibodies and progression to type 1 diabetes in three risk groups: 1) 3,869 islet autoantibody (IA)-negative children, of whom 157 became single IA positive; 2) 302 single IA-positive children, of whom 73 became multiple IA positive; and 3) 294 multiple IA-positive children, of whom 148 developed type 1 diabetes.

RESULTS: No significant association was found in risk group 1 or risk group 2. A significant association was seen in risk group 3 (hazard ratio 0.920 [95% CI 0.856, 0.988] per 10-min increase; P = 0.021), particularly when glutamate decarboxylase autoantibody was the first autoantibody (hazard ratio 0.883 [95% CI 0.783, 0.996] per 10-min increase; P = 0.043).

CONCLUSIONS: More daily minutes spent in moderate to vigorous physical activity was associated with a reduced risk of progression to type 1 diabetes in children aged 5-15 years who had developed multiple IAs.

Liu X, et al. Physical Activity and the Development of Islet Autoimmunity and Type 1 Diabetes in 5- to 15-Year-Old Children Followed in the TEDDY Study. Diabetes Care. 2023 Jul 1;46(7):1409-1416. doi: 10.2337/dc23-0036.

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8. Vitamin D3 Supplementation Improves the Effectiveness of ED Medication, Especially in Patients with Low Vit D Levels

ABSTRACT: This study aimed to compare the efficacy and risk of adverse events of sildenafil plus vitamin D3 versus sildenafil alone in improving erectile dysfunction (ED) in ED patients with low serum 25-hydroxy vitamin D3 (25-(OH)D3). The clinical data of ED patients with low serum 25-(OH)D3 treated at our center from December 2015 to December 2020 were retrieved, and the patients (n = 157) were randomly divided into an experimental group (n = 80) or a control group (n = 77). The experimental group was treated with 1 capsule of vitamin D3 (400u) daily for a month and advised to use 100 mg sildenafil (po) within 1 hour before sexual intercourse, while the control group was only given 100 mg sildenafil (po) 1 hour before sexual intercourse.

The indexes of international erectile function (IIEF-5), serum 25-(OH)D3 level, testosterone (T) level and adverse events between the two groups were compared before and after treatment. The results showed that the IIEF-5 values of the two groups were significantly higher after treatment than before treatment (p < 0.05). However, the serum levels of 25-(OH)D3 and T in the experimental group were significantly higher than before treatment (p < 0.05), while no significant differences were observed in the same markers in the control group before and after treatment (p > 0.05).

The overall effective rate, serum 25-(OH)D3 level and T level in the experimental group were significantly higher than the control group (p < 0.05). During the treatment, no significant difference in adverse events was observed between the two groups (p > 0.05), which mostly comprised mild and tolerable headache, dyspepsia, back pain and muscle soreness, not requiring any medical intervention. Although both methods could effectively treat ED patients with low 25-(OH)D3, the efficacy of sildenafil plus vitamin D3 was significantly superior to sildenafil alone, and the adverse reactions are mild and tolerable, which is worthy of clinical application.

Yang K, et al. Treating erectile dysfunction with sildenafil alone versus combined with vitamin D3 in patients with low serum 25-hydroxy vitamin D3: a prospective randomized controlled open trial. Journal of Men’s Health. 2023. 19(5);7-13.

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9. Low-Carbohydrate Diet may Cause Dysfunction in Glucose Homeostasis in Healthy Normal Weight Individuals

INTRODUCTION: Both obesity and a poor diet are considered major risk factors for triggering insulin resistance syndrome (IRS) and the development of type 2 diabetes mellitus (T2DM). Owing to the impact of low-carbohydrate diets, such as the keto diet and the Atkins diet, on weight loss in individuals with obesity, these diets have become an effective strategy for a healthy lifestyle. However, the impact of the ketogenic diet on IRS in healthy individuals of a normal weight has been less well researched. This study presents a cross-sectional observational study that aimed to investigate the effect of low carbohydrate intake in healthy individuals of a normal weight with regard to glucose homeostasis, inflammatory, and metabolic parameters.

METHODS: The study included 120 participants who were healthy, had a normal weight (BMI 25 kg/m2), and had no history of a major medical condition. Self-reported dietary intake and objective physical activity measured by accelerometry were tracked for 7 days. The participants were divided into three groups according to their dietary intake of carbohydrates: the low-carbohydrate (LC) group (those consuming <45% of their daily energy intake from carbohydrates), the recommended range of carbohydrate (RC) group (those consuming 45-65% of their daily energy intake from carbohydrates), and the high-carbohydrate (HC) group (those consuming more than 65% of their daily energy intake from carbohydrates). Blood samples were collected for the analysis of metabolic markers. HOMA of insulin resistance (HOMA-IR) and HOMA of β-cell function (HOMA-β), as well as C-peptide levels, were used for the evaluation of glucose homeostasis.

RESULTS: Low carbohydrate intake (<45% of total energy) was found to significantly correlate with dysregulated glucose homeostasis as measured by elevations in HOMA-IR, HOMA-β% assessment, and C-peptide levels. Low carbohydrate intake was also found to be coupled with lower serum bicarbonate and serum albumin levels, with an increased anion gap indicating metabolic acidosis. The elevation in C-peptide under low carbohydrate intake was found to be positively correlated with the secretion of IRS-related inflammatory markers, including FGF2, IP-10, IL-6, IL-17A, and MDC, but negatively correlated with IL-3.

DISCUSSION: Overall, the findings of the study showed that, for the first time, low-carbohydrate intake in healthy individuals of a normal weight might lead to dysfunctional glucose homeostasis, increased metabolic acidosis, and the possibility of triggering inflammation by C-peptide elevation in plasma.

Al-Reshed F, et al. Low carbohydrate intake correlates with trends of insulin resistance and metabolic acidosis in healthy lean individuals. Front Public Health. 2023 Mar 16;11:1115333.doi: 10.3389/fpubh.2023.1115333. eCollection 2023.

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10. Healthy Individuals Become Less Glucose Tolerant After 2 Weeks of Ingesting Artificial Sweeteners, which Adversely Affect the Microbiome

ABSTRACT: Non-nutritive sweeteners (NNS) are commonly integrated into human diet and presumed to be inert; however, animal studies suggest that they may impact the microbiome and downstream glycemic responses. We causally assessed NNS impacts in humans and their microbiomes in a randomized-controlled trial encompassing 120 healthy adults, administered saccharin, sucralose, aspartame, and stevia sachets for 2 weeks in doses lower than the acceptable daily intake, compared with controls receiving sachet-contained vehicle glucose or no supplement.

As groups, each administered NNS distinctly altered stool and oral microbiome and plasma metabolome, whereas saccharin and sucralose significantly impaired glycemic responses. Importantly, gnotobiotic mice conventionalized with microbiomes from multiple top and bottom responders of each of the four NNS-supplemented groups featured glycemic responses largely reflecting those noted in respective human donors, which were preempted by distinct microbial signals, as exemplified by sucralose. Collectively, human NNS consumption may induce person-specific, microbiome-dependent glycemic alterations, necessitating future assessment of clinical implications.

Suez J, et al. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. 2022 Sep 1;185(18):3307-3328.e19. doi: 10.1016/j.cell.2022.07.016. Epub 2022 Aug 19.

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11. Sucralose-6-Acetate Appears to Damage Rodent DNA and Induces Leaky Gut, Raising Concerns for Sucralose as a Safe Artificial Sweetener

ABSTRACT: The purpose of this study was to determine the toxicological and pharmacokinetic properties of sucralose-6-acetate, a structural analog of the artificial sweetener sucralose. Sucralose-6-acetate is an intermediate and impurity in the manufacture of sucralose, and recent commercial sucralose samples were found to contain up to 0.67% sucralose-6-acetate. Studies in a rodent model found that sucralose-6-acetate is also present in fecal samples with levels up to 10% relative to sucralose which suggest that sucralose is also acetylated in the intestines.

A MultiFlow® assay, a high-throughput genotoxicity screening tool, and a micronucleus (MN) test that detects cytogenetic damage both indicated that sucralose-6-acetate is genotoxic. The mechanism of action was classified as clastogenic (produces DNA strand breaks) using the MultiFlow® assay. The amount of sucralose-6-acetate in a single daily sucralose-sweetened drink might far exceed the threshold of toxicological concern for genotoxicity (TTCgenotox) of 0.15 µg/person/day. The RepliGut® System was employed to expose human intestinal epithelium to sucralose-6-acetate and sucralose, and an RNA-seq analysis was performed to determine gene expression induced by these exposures.

Sucralose-6-acetate significantly increased the expression of genes associated with inflammation, oxidative stress, and cancer with greatest expression for the metallothionein 1 G gene (MT1G). Measurements of transepithelial electrical resistance (TEER) and permeability in human transverse colon epithelium indicated that sucralose-6-acetate and sucralose both impaired intestinal barrier integrity. Sucralose-6-acetate also inhibited two members of the cytochrome P450 family (CYP1A2 and CYP2C19). Overall, the toxicological and pharmacokinetic findings for sucralose-6-acetate raise significant health concerns regarding the safety and regulatory status of sucralose itself.

Schiffman SS, et al. Toxicological and pharmacokinetic properties of sucralose-6-acetate and its parent sucralose: in vitro screening assays. J Toxicol Environ Health B Crit Rev. 2023 May 29;1-35. doi: 10.1080/10937404.2023.2213903. 

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12. Gel Based on Sage Extract Appears to Speed up Healing Time of Aphthous Ulcers

BACKGROUND: Recurrent Aphthous Stomatitis (RAS) is one of the most common lesions of the oral mucosa. Herbal medicine can be used for the treatment of this disease. The present study aimed to compare the effects of topical application of Sage (Salvizan) and triamcinolone acetonide gels on RAS.

METHODS: This double-blind clinical study recruited sixty patients with minor aphthous ulcers. Half of the patients were treated with Salvizan gel, and the other half were treated with oral triamcinolone acetonide gel. The effect of Salvizan topical gel was evaluated and compared with that of oral triamcinolone acetonide gel. Factors such as Pain recovery time, wound healing time, and pain level was evaluated. Data were analyzed by SPSS version 22 using independent t-test, paired t-test, repeated measures ANOVA, and survival analysis, including Kaplan-Meier and Cox regression.

RESULTS: The mean duration of pain recovery was 1.5 days for Salvizan and 2.5 days for triamcinolone acetonide (p < 0.001). Moreover, the duration of wound healing was 3.3 days for Salvizan and 6 days for triamcinolone acetonide (p < 0.001). Patients’ satisfaction from factors such as taste and smell had no significant difference between the two groups.

CONCLUSION: The results of this study showed that Salvizan gel is very effective in the treatment of RAS. It was significantly better than triamcinolone acetonide in the pain recovery and wound healing. These promising results favor herbal treatments and show that they can be used more commonly for treating diseases such as RAS.

Abbasi F, et al. The effect of sage (Salvizan gel) compared to triamcinolone acetonide on the treatment of recurrent aphthous stomatitis: a double-blinded randomized clinical trial. BMC Oral Health. 2023 Mar 18;23(1):157. doi: 10.1186/s12903-023-02861-y.

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