Effects of probiotic/synbiotic supplementation on body weight in patients with diabetes: a systematic review and meta-analyses of randomized-controlled trials.

OBJECTIVE: The aim of the present study was to assess the effect of probiotic/synbiotic supplementation on anthropometric measures in adults with diabetes, independent of body weight. METHODS: PubMed, Scopus, Web of Sciences and the Cochrane Library were searched for randomized controlled trials (RCTs) up until December 14, 2022. The effect sizes were pooled using an inverse-variance random-effects model. The methodological quality of studies as well as the quality of evidence was assessed using standard tools. RESULTS: Thirty-two RCTs met the established inclusion criteria. Overall, compared with the respective control groups, probiotic/synbiotic supplementation resulted in a significant reduction in body weight (weighted mean difference [WMD]: -0.50 kg; 95% CI: -0.83, -0.17; I2 = 79.8%, n = 27 studies]), body mass index (WMD: -0.24 kg/m2; 95% CI: -0.39, -0.09; I2 = 85.7%, n = 30 studies), and waist circumference (WMD: -0.90 cm; 95% CI: -1.13, -0.52; I2 = 0%, n = 11 studies). However, hip circumference and waist to hip ratio were not significantly improved. CONCLUSIONS: Our analysis revealed that probiotic/synbiotic supplementation may assist with weight management in patients with diabetes, especially when consumed at higher doses, in younger adults, and in participants with obesity. However, more studies are needed to elucidate the anti-obesity effects of specific strains of probiotics/synbiotics.

The effect of resveratrol supplementation on biomarkers of liver health: A systematic review and meta-analysis of randomized controlled trials.

This study aimed to evaluate the effect of resveratrol on liver biomarkers in adult participants, using systematic review and meta-analysis of randomized controlled trials. PubMed, Scopus, Web of Science and Cochran Library was searched, up to October 2021. The pooled effects were calculated using a random-effects model and expressed as weighted mean difference and 95% confidence interval. The methodological quality of studies as well as certainty of evidence were assessed by standard tools. Thirty-seven relevant trials were found. Although overall analysis found no significant change, subgroup analysis showed a significant improvement in alanine aminotransferase (ALT; -7.79 U/L) and glutamyl transferase (-6.0 U/L) in patients with liver disorders, and ALT (-2.22 U/L) in younger adults; however, high-dose supplementation (>1,000 mg/day) appeared to increase alkaline phosphatase concentration (+5.07 U/L). ALT also increased in older adults (+2.33 U/L) following resveratrol supplementation. We found resveratrol did not have a significant effect on liver health in the general population. However, resveratrol could be effective in patients with liver disorders. Our findings also suggest that high-dose resveratrol administration and supplementation in older adults should be performed with caution. Further high-quality clinical trials are also needed to firmly establish the clinical efficacy of resveratrol.

The effect of Vitamin C and Zn supplementation on the immune system and clinical outcomes in COVID-19 patients.

SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) is the most dangerous form of the coronavirus, which causes COVID-19. In patients with severe COVID-19, the immune system becomes markedly overactive. There is evidence that supplementation with select micronutrients may play a role in maintaining immune system function in this patient population. Throughout the COVID-19 pandemic, significant emphasis has been placed on the importance of supplementing critical micronutrients such as Vitamin C and Zinc (Zn) due to their immunomodulatory effects. Viral infections, like COVID-19, increase physiological demand for these micronutrients. Therefore, the purpose of this review was to provide comprehensive information regarding the potential effectiveness of Vitamin C and Zn supplementation during viral infection and specifically COVID-19. This review demonstrated a relation between Vitamin C and Zn deficiency and a reduction in the innate immune response, which can ultimately make patients with COVID-19 more vulnerable to viral infection. As such, adequate intake of Vitamin C and Zn, as an adjunctive therapeutic approach with any necessary pharmacological treatment(s), may be necessary to mitigate the adverse physiological effects of COVID-19. To truly clarify the role of Vitamin C and Zn supplementation in the management of COVID-19, we must wait for the results of ongoing randomized controlled trials. The toxicity of Vitamin C and Zn should also be considered to prevent over-supplementation. Over-supplementation of Vitamin C can lead to oxalate toxicity, while increased Zn intake can reduce immune system function. In summary, Vitamin C and Zn supplementation may be useful in mitigating COVID-19 symptomology.

Sodium status is associated with type 2 diabetes mellitus: a systematic review and meta-analysis of observational studies.

PURPOSE: The relationship between sodium intake and the risk of developing type 2 diabetes mellitus (T2DM) is inconsistent. We, therefore, aimed to summarize the current evidence by conducting a systematic review and meta-analysis of observational studies. METHODS: We retrieved studies which compared any marker of sodium status between individuals with T2DM and those without diabetes published in any language by searching online databases from inception up to June 2019. Summary effects were derived using random-effects model. RESULTS: A total of 44 studies with 503,830 participants from 25 countries were included in this study. Sodium status was significantly different between individuals with and without T2DM (Hedges' g = 0.21; 95% CI 0.02, 0.40; P = 0.029). Individuals with T2DM had higher sodium intake compared to non-diabetic controls (WMD = 621.79 mg/day; 95% CI 321.53, 922.06; P < 0.001) and 24-h urinary excretion was associated with likelihood of developing T2DM (OR = 1.27, 95% CI 1.15, 1.41; P < 0.001). Furthermore, salivary, hair, and platelet sodium were higher in patients with T2DM compared to controls (P < 0.05). CONCLUSION: The findings of the current meta-analysis suggest that sodium levels are higher in patients with T2DM compared to non-diabetic controls; however, given that these studies are observational, it is not possible to infer causality.

Glial Activation in the Thalamus Contributes to Vestibulomotor Deficits Following Blast-Induced Neurotrauma.

Vestibular impairment has become a frequent consequence following blast-related traumatic brain injury (bTBI) in military personnel and Veterans. Behavioral outcomes such as depression, fear and anxiety are also common comorbidities of bTBI. To accelerate pre-clinical research and therapy developments, there is a need to study the link between behavioral patterns and neuropathology. The transmission of neurosensory information often involves a pathway from the cerebral cortex to the thalamus, and the thalamus serves crucial integrative functions within vestibular processing. Pathways from the thalamus also connect with the amygdala, suggesting thalamic and amygdalar contributions to anxiolytic behavior. Here we used behavioral assays and immunohistochemistry to determine the sub-acute and early chronic effects of repeated blast exposure on the thalamic and amygdala nuclei. Behavioral results indicated vestibulomotor deficits at 1 and 3 weeks following repeated blast events. Anxiety-like behavior assessments depicted trending increases in the blast group. Astrogliosis and microglia activation were observed upon post-mortem pathological examination in the thalamic region, along with a limited glia response in the amygdala at 4 weeks. These findings are consistent with a diffuse glia response associated with bTBI and support the premise that dysfunction within the thalamic nuclei following repeated blast exposures contribute to vestibulomotor impairment.

The responses of different dosages of egg consumption on blood lipid profile: An updated systematic review and meta-analysis of randomized clinical trials.

Diverse notions exist regarding egg intake, which is one of the main sources of dietary cholesterol, and its effect on blood lipids. We conducted this study to update the previous meta-analysis for their flaw in calculated effect size. PubMed, Scopus, ISI, and Cochrane were searched up to April 2019, for relevant randomized controlled clinical trials. Mean changes in total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglyceride (TG), very low-density lipoprotein cholesterol (VLDL-C), LDL-C/HDL-C, TC/HDL-C, apolipoprotein (apo)A1, and apoB100 were assessed. Meta-analysis of 66 RCTs with 3,185 participants revealed that egg consumption can significantly increase TC, LDL-C, HDL-C, TC/HDL-C, apoA1/and B100, but there was no significant effect on other serum lipids. Dose-response analysis showed a linear effect for TC, HDL-C, ApoA1, ApoB100, and nonlinear for LDL-C, and TC/HDL-C. In conclusion, intake of more than one egg daily in less than 12 weeks may increase some blood lipids without any changes in the ratio of LDL-C/HDL-C. PRACTICAL APPLICATIONS: There are controversies reports for egg intake, which is one of the main sources of dietary cholesterol. This study provides comprehensive information about the effect of the number of eggs consumed per day (dietary cholesterol) on blood lipids for nutritionists, physicians, researchers, and the general population. In this regard, our results indicated that there is a linear correlation between consumption of greater than one egg per day in a short time (no long time) and increasing lipid profiles which may increase the risk of cardiovascular diseases. However, consumption of one egg daily can be safe and this can be a useful recommendation for prevention of cardiovascular disease and promotion of healthy life which indeed are the potential or actual uses of this research.

Effect of Egg Consumption on Blood Pressure: a Systematic Review and Meta-analysis of Randomized Clinical Trials.

PURPOSE OF REVIEW: We identified and quantified the results of randomized controlled trials (RCTs) that have assessed the impact of egg consumption on blood pressure in adults. RECENT FINDINGS: We conducted a comprehensive search of medical bibliographic databases up to February 2019 for RCTs investigating the effect of egg consumption on blood pressure in adults. Fifteen RCTs were included with a total of 748 participants. Overall, egg consumption had no significant effect on systolic blood pressure (weighted mean difference (WMD) = 0.046 mmHg; 95% CI - 0.792, 0.884) and diastolic blood pressure (WMD = - 0.603 mmHg; 95% CI - 1.521, 0.315). Subgroup analyses had no effect on pooled results and no heterogeneity was found among included studies. Egg consumption has no significant effects on systolic and diastolic blood pressure in adults. Due to several limitations among existing studies, general conclusions cannot be drawn regarding the beneficial or neutral impact of egg consumption on blood pressure in adults.

Differing Impact of Weight Cycling on Ambulatory Blood Pressure versus Conventional Blood Pressure Assessment: A Possible Explanation to Controversy.

BACKGROUND: Weight cycling (WC) is a widespread behavior associated with elevated laboratory blood pressure (BP). The impact WC may have on ambulatory BP (ABP) is unknown. METHODS: Impact of self-reported WC history on ABP was assessed via cross-sectional nonexperimental design. Sixty-five women completed the Weight and Lifestyle Inventory (WALI) questionnaire. The WALI has been shown to be a reliable index of WC (r=0.87, P<0.001). Data were analyzed looking at WC both as a continuous and criterion variable, and subjects were dichotomized as either WC or non-WC (NWC). RESULTS: WC (n=31) were older (39.7±8.9 vs. 33.1±11.3 years), had a higher percent body fat (47.1%±6.2% vs. 41.4%±7.8%), and were less fit (21.2±5.4 vs. 26.7±7.6 mL/kg/min) than NWC (n=34). No significant correlation between laboratory systolic BP (SBP, P=0.830) or diastolic BP (DBP, P=0.997) and WC was observed. A significant correlation between the number of WC and systolic ABP (r=0.326, P=0.010) and trend for diastolic ABP (r=0.238, P=0.065) was found. SBP (23% vs. 17%, P<0.001) and DBP (13% vs. 9%, P<0.001) load was higher for WC compared to NWC women. CONCLUSION: WC may deleteriously affect BP outcomes that might only be observed when ABP monitoring is used.

Effect of egg consumption on inflammatory markers: a systematic review and meta-analysis of randomized controlled clinical trials.

There is little evidence about whether eggs affect inflammation. The aim of this meta-analysis was to explore the effects of egg consumption on inflammation. A systematic search of online databases (Institute for Scientific Information (ISI), Scopus, Ovid, PubMed, Cochrane) was used to gather clinical trials that assessed the effect of egg consumption on circulating inflammatory biomarkers. Using a random-effects model, pooled weighted mean differences (WMD) and corresponding standard deviations (SD) were calculated. Of the 21 eligible studies found, nine trials were eligible for analysis. Eight trials assessed high-sensitivity C-reactive protein (hs-CRP), four trials assessed interleukin-6 (IL-6), and five trials assessed tumor necrosis factor-alpha (TNF-α). Egg consumption did not affect hs-CRP (WMD 0.24 mg/L; 95% CI: -0.43, 0.90; I2  = 53.8; P = 0.48), IL-6 (WMD 0.20 pg/mL; 95% CI: -0.71, 1.11; I2 = 69.3; P = 0.50), and TNF-α (WMD: -0.38 pg/mL; 95% CI: -0.87, 0.10; I2 = 0.00; P = 0.12) relative to controls. Overall, this meta-analysis revealed that egg consumption had no significant effect on serum biomarkers of inflammation in adults. © 2019 Society of Chemical Industry.

Voltage-Gated Calcium Influx Modifies Cholinergic Inhibition of Inner Hair Cells in the Immature Rat Cochlea.

Until postnatal day (P) 12, inner hair cells of the rat cochlea are invested with both afferent and efferent synaptic connections. With the onset of hearing at P12, the efferent synapses disappear, and afferent (ribbon) synapses operate with greater efficiency. This change coincides with increased expression of voltage-gated potassium channels, the loss of calcium-dependent electrogenesis, and the onset of graded receptor potentials driven by sound. The transient efferent synapses include near-membrane postsynaptic cisterns thought to regulate calcium influx through the hair cell's α9-containing and α10-containing nicotinic acetylcholine receptors. This influx activates small-conductance Ca2+-activated K+ (SK) channels. Serial-section electron microscopy of inner hair cells from two 9-d-old (male) rat pups revealed many postsynaptic efferent cisterns and presynaptic afferent ribbons whose average minimal separation in five cells ranged from 1.1 to 1.7 µm. Efferent synaptic function was studied in rat pups (age, 7-9 d) of either sex. The duration of these SK channel-mediated IPSCs was increased by enhanced calcium influx through L-type voltage-gated channels, combined with ryanodine-sensitive release from internal stores-presumably the near-membrane postsynaptic cistern. These data support the possibility that inner hair cell calcium electrogenesis modulates the efficacy of efferent inhibition during the maturation of inner hair cell synapses.SIGNIFICANCE STATEMENT Strict calcium buffering is essential for cellular function. This problem is especially acute for compact hair cells where increasing cytoplasmic calcium promotes the opposing functions of closely adjoining afferent and efferent synapses. The near-membrane postsynaptic cistern at efferent synapses segregates synaptic calcium signals by acting as a dynamic calcium store. The hair cell serves as an informative model for synapses with postsynaptic cisterns (C synapses) found in central neurons.

Re-Emergent Inhibition of Cochlear Inner Hair Cells in a Mouse Model of Hearing Loss.

Hearing loss among the elderly correlates with diminished social, mental, and physical health. Age-related cochlear cell death does occur, but growing anatomical evidence suggests that synaptic rearrangements on sensory hair cells also contribute to auditory functional decline. Here we present voltage-clamp recordings from inner hair cells of the C57BL/6J mouse model of age-related hearing loss, which reveal that cholinergic synaptic inputs re-emerge during aging. These efferents are functionally inhibitory, using the same ionic mechanisms as do efferent contacts present transiently before the developmental onset of hearing. The strength of efferent inhibition of inner hair cells increases with hearing threshold elevation. These data indicate that the aged cochlea regains features of the developing cochlea and that efferent inhibition of the primary receptors of the auditory system re-emerges with hearing impairment. SIGNIFICANCE STATEMENT: Synaptic changes in the auditory periphery are increasingly recognized as important factors in hearing loss. To date, anatomical work has described the loss of afferent contacts from cochlear hair cells. However, relatively little is known about the efferent innervation of the cochlea during hearing loss. We performed intracellular recordings from mouse inner hair cells across the lifespan and show that efferent innervation of inner hair cells arises in parallel with the loss of afferent contacts and elevated hearing threshold during aging. These efferent neurons inhibit inner hair cells, raising the possibility that they play a role in the progression of age-related hearing loss.

Retrograde facilitation of efferent synapses on cochlear hair cells.

Cochlear inner hair cells (IHCs) are temporarily innervated by efferent cholinergic fibers prior to the onset of hearing. During low-frequency firing, these efferent synapses have a relatively low probability of transmitter release but facilitate strongly with repetitive stimulation. A retrograde signal from the hair cell to the efferent terminal contributes to this facilitation. When IHCs were treated with the ryanodine receptor agonist, cyclic adenosine phosphoribose (cADPR), release probability of the efferent terminal rose. This effect was quantified by computing the quantum content from a train of 100 suprathreshold stimuli to the efferent fibers. Quantum content was sevenfold higher when IHCs were treated with 100 µM cADPR (applied in the recording pipette). Since cADPR is membrane impermeant, this result implies that an extracellular messenger travels from the hair cell to the efferent terminal. cADPR is presumed to generate this messenger by increasing cytoplasmic calcium. Consistent with this presumption, voltage-gated calcium flux into the IHC also caused retrograde facilitation of efferent transmission. Retrograde facilitation was observed in IHCs of a vesicular glutamate transporter (VGlut3) null mouse and for wild-type rat hair cells subject to wide-spectrum glutamate receptor blockade, demonstrating that glutamate was unlikely to be the extracellular messenger. Rather, bath application of nitric oxide (NO) donors caused an increase in potassium-evoked efferent transmitter release while the NO scavenger carboxy-PTIO was able to prevent retrograde facilitation produced by cADPR or IHC depolarization. Thus, hair cell activity can drive retrograde facilitation of efferent input via calcium-dependent production of NO.