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Beneficial Effects of the Very-Low-Calorie Ketogenic Diet on the Symptoms of Male Accessory Gland Inflammation.
Condorelli, RA, Aversa, A, Basile, L, Cannarella, R, Mongioì, LM, Cimino, L, Perelli, S, Caprio, M, Cimino, S, Calogero, AE, et al
Nutrients. 2022;(5)
Abstract
Introduction. Obesity exposes individuals to the risk of chronic inflammation of the prostate gland. Aim and design of the study. A longitudinal clinical study was conducted on selected overweight/obese patients with male accessory gland inflammation (MAGI) to evaluate the effects of body weight loss on their urogenital symptoms. Materials and methods. One hundred patients were selected and assigned to two groups undergoing two different nutritional programs. The first group (n = 50) started a Mediterranean diet (MedDiet) and the second (n = 50) a very-low-calorie ketogenic diet (VLCKD). Before and after three months on the diet, each patient was evaluated for body weight, waist circumference, and MAGI symptoms. The MAGI was assessed using the Structured Interview about MAGI (SI-MAGI), a questionnaire previously designed to assess the symptoms of MAGI. The questionnaire explores four domains, including urinary symptoms, ejaculatory pain or discomfort, sexual dysfunction, and impaired quality of life. Finally, in the two groups, the frequency of an α-blocker used to treat urinary tract symptoms was also evaluated. Results. Patients on MedDiet experienced significant amelioration in urinary symptoms and quality of life. Patients under VLCKD reported not only significant improvement of the same parameters, but also in ejaculatory pain/discomfort and sexual dysfunction. Finally, the percentage of patients on VLCKD taking the α-blocker decreased significantly. Moreover, patients under VLCKD showed a greater loss of body weight than those following the MedDiet. Discussion. The results of this study support the effectiveness of VLCKD in improving the symptoms of patients with MAGI. This improvement involved all of the domains of the SI-MAGI questionnaire and became manifest in a relatively short time. We suggest that a ketogenic nutritional approach can be used in overweight/obese patients with MAGI.
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DNA Methylation in Offspring Conceived after Assisted Reproductive Techniques: A Systematic Review and Meta-Analysis.
Cannarella, R, Crafa, A, Mongioì, LM, Leggio, L, Iraci, N, La Vignera, S, Condorelli, RA, Calogero, AE
Journal of clinical medicine. 2022;(17)
Abstract
Background: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate whether ART is associated with epigenetic dysregulation in the offspring. Methods. To accomplish this, we collected all available data on methylation patterns in offspring conceived after ART and in spontaneously conceived (SC) offspring. Results. We extracted 949 records. Of these, 50 were considered eligible; 12 were included in the quantitative synthesis. Methylation levels of H19 CCCTC-binding factor 3 (CTCF3) were significantly lower in the ART group compared to controls (SMD -0.81 (-1.53; -0.09), I2 = 89%, p = 0.03). In contrast, H19 CCCTC-binding factor 6 (CTCF6), Potassium Voltage-Gated Channel Subfamily Q Member 1 (KCNQ1OT1), Paternally-expressed gene 3 (PEG3), and Small Nuclear Ribonucleoprotein Polypeptide N (SNRPN) were not differently methylated in ART vs. SC offspring. Conclusion: The methylation pattern of the offspring conceived after ART may be different compared to spontaneous conception. Due to the lack of studies and the heterogeneity of the data, further prospective and well-sized population studies are needed to evaluate the impact of ART on the epigenome of the offspring.
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Advances in non-hormonal pharmacotherapy for the treatment of male infertility: the role of inositols.
Condorelli, RA, Cannarella, R, Crafa, A, Barbagallo, F, Gusmano, C, Avola, O, Mongioì, LM, Basile, L, Calogero, AE, La Vignera, S
Expert opinion on pharmacotherapy. 2022;(9):1081-1090
Abstract
INTRODUCTION Several antioxidants are available for the treatment of male infertility. Although the benefit of myo-inositol (MYO) and D-chiro-inositol (DCI) for female infertility is recognized, their role in male infertility is a matter of debate. AREAS COVERED The authors review the impact that treatment with MYO and/or DCI may have on conventional and bio-functional sperm parameters [mitochondrial membrane potential (MMP), sperm chromatin compactness, and sperm DNA fragmentation (SDF)], seminal oxidative stress (OS), and pregnancy, miscarriage, and live birth rates, and the possible mechanisms involved. Furthermore, the authors gather evidence on the effects of MYO and/or DCI on sperm function in vitro. EXPERT OPINION MYO can improve sperm count, motility, capacitation, acrosome reaction, and MMP. No data are currently available on the effects of DCI in vivo. Both MYO and DCI ameliorate sperm motility and MMP in vitro. Therefore, the use of inositols should be preferred in patients with idiopathic asthenozoospermia, especially in case of impaired sperm mitochondrial function. Due to their insulin-sensitizing action, a role for these molecules may be envisaged for the treatment of infertility caused by carbohydrate metabolism derangement.
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The Role of Resveratrol Administration in Human Obesity.
Mongioì, LM, La Vignera, S, Cannarella, R, Cimino, L, Compagnone, M, Condorelli, RA, Calogero, AE
International journal of molecular sciences. 2021;(9)
Abstract
Obesity is a widespread disease that is associated with numerous and serious comorbidities. These include metabolic syndrome, diabetes mellitus, cardiovascular-cerebrovascular disease, hypertension, obstructive sleep apnea syndrome, cancer, and sexual and hormonal disorders. The treatment of obesity has therefore become a goal of great clinical and social relevance. Among the therapeutic strategies against obesity, resveratrol has aroused great interest. This polyphenol has anticancer and antioxidant properties and cytoprotective and anti-inflammatory effects. Other favorable effects attributed to resveratrol are anti-lipid, anti-aging, anti-bacterial, anti-viral, and neuroprotective actions. Administration of resveratrol appears to improve the metabolic profile in obese and/or insulin-resistant patients. This article aims to review the main results of clinical studies evaluating the effects of administering resveratrol alone in overweight/obese patients.
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Relevance of sperm imprinted gene methylation on assisted reproductive technique outcomes and pregnancy loss: a systematic review.
Cannarella, R, Crafa, A, Condorelli, RA, Mongioì, LM, La Vignera, S, Calogero, AE
Systems biology in reproductive medicine. 2021;(4):251-259
Abstract
Recent evidence suggests that gamete-imprinted genes play a role in embryo and placenta development and growth. This systematic review aimed to evaluate whether altered methylation of sperm-imprinted genes associates with sperm DNA fragmentation (SDF), pregnancy loss rate and assisted reproductive technique (ART) outcome. To accomplish this, Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases were used for search strategy from each database inception until December 2020. Specific keywords were used. Studies satisfying the PECOS (Population, Exposure, Comparison/Comparator, Outcomes, Study design) model were retrieved. Ten studies could be included in the qualitative analysis. A significant association was reported between increased SDF rate and aberrant methylation of H19/IGF2 and KCNQ1 genes by two studies. A significantly lower H19 methylation was found in patients with idiopathic recurrent pregnancy loss (RPL) and in infertile patients compared to fertile men. Methylation of GLT2, PEG1/MEST, and ZAC/PLACL1 were similar in patients with RPL and controls. The ART outcome was similar in patients with aberrant and normal methylation of H19, SNRPN, KCNQ1OT1, PEG1/MEST, LIT1, PEG3, NESPAS, and GLT2. By contrast, a study showed an association between altered GLT2 methylation and more inferior ART results. If further confirmed by well-sized studies, these data might be helpful to identify possible epigenetic predictors of ART outcome. Particularly, aberrant methylation of H19/IGF2 and KCNQ1 genes might represent interesting targets that deserve further investigation.
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Very-low-calorie ketogenic diet: An alternative to a pharmacological approach to improve glycometabolic and gonadal profile in men with obesity.
Mongioì, LM, Cimino, L, Greco, E, Cannarella, R, Condorelli, RA, La Vignera, S, Calogero, AE
Current opinion in pharmacology. 2021;:72-82
Abstract
Obesity and metabolic diseases have become a worrying reality, especially in more developed societies. They are associated with the development of many comorbidities, such as type 2 diabetes mellitus, hypogonadism, hypertension, cerebrovascular and cardiovascular diseases, neoplasia, obstructive sleep apnea, and non-alcoholic fatty liver disease. Therefore, weight loss is of paramount importance. A promising therapeutic option to achieve this goal is the very-low-calorie ketogenic diet. This review aims to summarize the main effects of very-low-calorie-ketogenic diet on the glycometabolic and gonadal profiles of men with overweight/obesity.
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The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study.
La Vignera, S, Cannarella, R, Galvano, F, Grillo, A, Aversa, A, Cimino, L, Magagnini, CM, Mongioì, LM, Condorelli, RA, Calogero, AE
Endocrine. 2021;(2):392-399
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Abstract
BACKGROUND Overweight and obesity are increasingly spread in our society. Low testosterone levels are often present in these patients, the so-called metabolic hypogonadism, that further alters the metabolic balance in a sort of vicious cycle. Very low-calorie ketogenic diet (VLCKD) has been reported to efficiently reduce body weight, glycaemia, and the serum levels of insulin, glycated hemoglobin, but its effects on β-cell function and total testosterone (TT) levels are less clear. AIM: To evaluate the effects of VLCKD on markers suggested to be predictive of β-cell dysfunction development, such as proinsulin or proinsulin/insulin ratio, and on TT values in a cohort of overweight or obese nondiabetic male patients with metabolic hypogonadism. METHODS Patients with overweight or obesity and metabolic hypogonadism underwent to VLCKD for 12 weeks. Anthropometric parameters, blood testing for the measurement of glycaemia, insulin, C-peptide, proinsulin, TT, calculation of body-mass index (BMI), and HOMA index were performed before VLCKD and after 12 weeks. RESULTS Twenty patients (mean age 49.3 ± 5.2 years) were enrolled. At enrollement all patients presented increased insulin, HOMA index, C-peptide, and proinsulin levels, whereas the proinsulin/insulin ratio was within the normal values. After VLCKD treatment, body weight and BMI significantly decreased, and 14.9 ± 3.9% loss of the initial body weight was achieved. Glycaemia, insulin, HOMA index, C-peptide, and proinsulin significantly decreased compared to pre-VLCKD levels. Serum glycaemia, insulin, C-peptide, and proinsulin levels returned within the normal range in all patients. No difference in the proinsulin/insulin ratio was observed after VLCKD treatment. A mean increase of 218.1 ± 53.9% in serum TT levels was achieved and none of the patients showed TT values falling in the hypogonadal range at the end of the VLCKD treatment. CONCLUSIONS This is the first study that evaluated the effects of VLCKD on proinsulin, proinsulin/insulin ratio, and TT levels. VLCKD could be safely used to improve β-cell secretory function and insulin-sensitivity, and to rescue overweight and obese patients from β-cell failure and metabolic hypogonadism.
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The Role of Resveratrol in Human Male Fertility.
Mongioì, LM, Perelli, S, Condorelli, RA, Barbagallo, F, Crafa, A, Cannarella, R, La Vignera, S, Calogero, AE
Molecules (Basel, Switzerland). 2021;(9)
Abstract
Resveratrol (RSV) (3,4',5 trihydroxystilbene) is a natural non-flavonoid polyphenol widely present in the Mediterranean diet. In particular, RSV is found in grapes, peanuts, berries, and red wine. Many beneficial effects of this molecule on human health have been reported. In fact, it improves some clinical aspects of various diseases, such as obesity, tumors, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, and diabetes mellitus. However, little is known about the relationship between this compound and male fertility and the few available results are often controversial. Therefore, this review evaluated the effects of RSV on human male fertility and the mechanisms through which this polyphenol could act on human spermatozoa.
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Influence of 25-hydroxy-cholecalciferol levels on SARS-CoV-2 infection and COVID-19 severity: A systematic review and meta-analysis.
Crafa, A, Cannarella, R, Condorelli, RA, Mongioì, LM, Barbagallo, F, Aversa, A, La Vignera, S, Calogero, AE
EClinicalMedicine. 2021;:100967
Abstract
BACKGROUND The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 19 (COVID-19), a respiratory infection that, starting from December 2019, has spread around the world in a few months, becoming a pandemic. The lack of initial knowledge on its management has led to a great effort in developing vaccines and in finding therapeutic weapons capable of improving the clinical outcome of the affected patients. In particular, the possible role of vitamin D status in the management of COVID-19 has been widely analysed, resulting in a great amount of data. This systematic review and meta-analysis aimed to assess whether hypovitaminosis D is a risk factor for developing SARS-CoV-2 infection and whether it affects the worsening of the clinical course of COVID-19. METHODS Data were extracted through extensive searches in the Pubmed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases from December 2019 to January 2021, using the keywords: "Vitamin D", "25 hydroxy Vitamin D", "25 hydroxycholecalciferol", "cholecalciferol", "COVID 19″, "SARS-CoV-2″. We included observational cohort, cross-sectional, and case-control studies that evaluated differences in serum levels of 25‑hydroxy-cholecalciferol [25(OH)D] in patients who were positive or negative for SARS-CoV-2, in patients with mild or severe forms of COVID-19, and in patients who died or were discharged from the hospital. Finally, studies that evaluated the risk of developing severe illness or death in patients with vitamin D deficiency (VDD), defined as levels of 25(OH)D <20 ng/ml, were also included. We calculated the mean difference (MD) and the 95% confidence intervals (CI) for quantitative variables such as 25(OH)D levels in patients with or without SARS-CoV-2 infection, in those with mild vs. severe COVID-19, or those who have died vs. those who have been discharged. Instead, we calculated odds ratios and 95% CI for qualitative ones, such as the number of patients with severe illness/death in the presence of VDD vs. those with normal serum 25(OH)D levels. A p-value lower than 0.05 was considered statistically significant. The study was registered on PROSPERO (CRD42021241473). FINDINGS Out of 662 records, 30 articles met inclusion criteria and, therefore, were included in the meta-analysis. We found that the serum levels of 25(OH)D were significantly lower in patients with SARS-CoV-2 infection than in negative ones [MD -3.99 (-5.34, -2.64); p <0.00001; I2= 95%]. Furthermore, its levels were significantly lower in patients with severe disease [MD -6.88 (-9.74, -4.03); p <0.00001; I2=98%] and in those who died of COVID-19 [MD -8.01 (-12.50, -3.51); p = 0.0005; I2=86%]. Finally, patients with VDD had an increased risk of developing severe disease [OR 4.58 (2.24, 9.35); p <0.0001; I2=84%] but not a fatal outcome [OR 4.92 (0.83, 29.31); p = 0.08; I2=94%]. INTERPRETATION This meta-analysis revealed a large heterogeneity of the studies included due to the different enrolment criteria of patient samples (age, body mass index, ethnicity, comorbidities), the country where they live, all factors influencing serum 25(OH)D levels, and the different criteria used to define the severity of COVID-19. Furthermore, the observational nature of these studies does not allow to establish a cause-effect relationship, even taking into account that 25(OH)D represents a marker of acute inflammation. Treatment with vitamin D might be considered for the primary prevention of SARS-CoV-2 infection and the management of patients with COVID-19. However, further intervention studies are needed to prove this hypothesis.
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Possible long-term endocrine-metabolic complications in COVID-19: lesson from the SARS model.
Mongioì, LM, Barbagallo, F, Condorelli, RA, Cannarella, R, Aversa, A, La Vignera, S, Calogero, AE
Endocrine. 2020;68(3):467-470
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Plain language summary
Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Little is known about how it affects the endocrine system and it is likely that some patients who have recovered may suffer long-term consequences. The severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the SARS outbreak in 2003 has many similarities. This editorial looks at the possible effects on the endocrine system of SARS-CoV-2 by looking at the long-term effects seen in SARS. In the case of SARS-CoV, it was thought that the virus could directly damage pancreatic cells leading to type 2 diabetes. It is hypothesized that Covid-19 patients could develop this condition by the same mechanism. Although no study on SARS reported the link between obesity and higher mortality rate, there is evidence that obese Covid-19 patients have worse clinical outcomes. There is no data yet for Covid-19, but adrenal insufficiency and impaired thyroid function were shown in some cases of SARS. To identify and treat any possible long-term effects of Covid-19, endocrinologists should monitor hormone levels and metabolic functions.
Abstract
The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is centralizing the interest of the scientific world. In the next months, long-term consequences on the endocrine system may arise following COVID-19. In this article, we hypothesized the effects of SARS-CoV-2 taking into account what learned from the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused SARS in 2003.