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Testosterone does not affect lower urinary tract symptoms while improving markers of prostatitis in men with benign prostatic hyperplasia: a randomized clinical trial.
Rastrelli, G, Cipriani, S, Lotti, F, Cellai, I, Comeglio, P, Filippi, S, Boddi, V, Della Camera, PA, Santi, R, Boni, L, et al
Journal of endocrinological investigation. 2022;45(7):1413-1425
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Plain language summary
Benign prostatic hyperplasia (BPH) — also called benign prostate enlargement — is frequent in aging populations, with a 40 – 50% prevalence in men aged 50–60 years and up to 90% in men older than 80 years. The aim of this study was to verify whether testosterone therapy (TTh) in men with BPH, metabolic syndrome (MetS) and low testosterone is able to improve lower urinary tract symptoms (LUTS) and intraprostatic inflammation. This study is a double blind, randomised 24-week clinical trial in men with low testosterone and MetS and a candidate for prostate surgery for BPH. Patients (n=144) were centrally randomised 1:1 to one of the two groups; TTh or placebo. Results show that TTh administered for 24 weeks is a safe option and it improves prostatic inflammatory features thus ameliorating one of the pathogenic components of BPH. However, there were no differences in improvements of the urinary symptoms between both groups (TTh and placebo). Authors conclude that decreased inflammation is not accompanied by a consistent improvement in urinary symptoms, and that their findings show the safety of TTh in subjects with BPH of surgical significance.
Abstract
PURPOSE Benign Prostatic Hyperplasia (BPH) is a result of prostate inflammation, frequently occurring in metabolic syndrome (MetS). Low testosterone is common in MetS. A randomized clinical trial was designed to evaluate if 24 weeks of testosterone therapy (TTh) in BPH men with MetS and low testosterone improve urinary symptoms and prostate inflammation. METHODS One-hundred-twenty men with MetS waitlisted for BPH surgery were enrolled. They were categorized into normal testosterone (TT ≥ 12 nmol/L and cFT ≥ 225 pmol/L; n = 48) and testosterone deficient (TD) (TT < 12 nmol/L and/or cFT < 225 pmol/L; n = 72) then randomized to testosterone gel 2% (5 g/daily) or placebo for 24 weeks. At baseline and follow-up, questionnaires for urinary symptoms and trans-rectal ultrasound were performed. Prostate tissue was collected for molecular and histopathological analyses. RESULTS No differences in the improvement of urinary symptoms were found between TTh and placebo (OR [95% CI] 0.96 [0.39; 2.37]). In TD + TTh, increase in prostate but not adenoma volume was observed (2.64 mL [0.07; 5.20] and 1.82 mL [- 0.46; 0.41], respectively). Ultrasound markers of inflammation were improved. In a subset of 61 men, a hyper-expression of several pro-inflammatory genes was found in TD + placebo when compared with normal testosterone. TTh was able to counteract this effect. For 80 men, the inflammatory infiltrate was higher in TD + placebo than in normal testosterone (0.8 points [0.2; 1.4]) and TD + TTh men (0.9 points [0.2; 1.5]). CONCLUSIONS Twenty-four weeks of TTh in TD men with BPH and MetS improves ultrasound, molecular and histological proxies of prostate inflammation. This does not result in symptom improvement.
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Nicotinamide Riboside Enhances In Vitro Beta-adrenergic Brown Adipose Tissue Activity in Humans.
Nascimento, EBM, Moonen, MPB, Remie, CME, Gariani, K, Jörgensen, JA, Schaart, G, Hoeks, J, Auwerx, J, van Marken Lichtenbelt, WD, Schrauwen, P
The Journal of clinical endocrinology and metabolism. 2021;106(5):1437-1447
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Brown fat is a type of fat that burns energy to regulate the body’s temperature in cold conditions. A high level of activity in the brown fat has been associated with healthy whole-body metabolism. Several supplements have been investigated for their potential to activate brown fat, however many of these have limiting side effects. Nicotinamide riboside (NR), also known as vitamin B3, is a supplement which can boost energy burning pathways within the body. This randomised control trial was part of a larger trial including a study on human brown fat cells and aimed to determine whether NR supplementation in overweight and obese individuals may act on the activity of brown tissue. The results showed that 6 weeks of NR supplementation had no effect on brown tissue activity or energy expenditure. It was concluded that NR supplementation for 6 weeks in individuals with obesity had no effect on brown fat tissue for reasons unknown, as the cellular study showed an increase in activity. This study could be used by healthcare professionals to better understand the role of brown fat in metabolism.
Abstract
CONTEXT Elevating nicotinamide adenine dinucleotide (NAD+) levels systemically improves metabolic health, which can be accomplished via nicotinamide riboside (NR). Previously, it was demonstrated that NR supplementation in high-fat-diet (HFD)-fed mice decreased weight gain, normalized glucose metabolism, and enhanced cold tolerance. OBJECTIVE Because brown adipose tissue (BAT) is a major source of thermogenesis, we hypothesize that NR stimulates BAT in mice and humans. DESIGN AND INTERVENTION HFD-fed C56BL/6J mice were supplemented with 400 mg/kg/day NR for 4 weeks and subsequently exposed to cold. In vitro primary adipocytes derived from human BAT biopsies were pretreated with 50 µM or 500 µM NR before measuring mitochondrial uncoupling. Human volunteers (45-65 years; body mass index, 27-35 kg/m2) were supplemented with 1000 mg/day NR for 6 weeks to determine whether BAT activity increased, as measured by [18F]FDG uptake via positron emission tomography-computed tomography (randomized, double blinded, placebo-controlled, crossover study with NR supplementation). RESULTS NR supplementation in HFD-fed mice decreased adipocyte cell size in BAT. Cold exposure further decreased adipocyte cell size on top of that achieved by NR alone independent of ex vivo lipolysis. In adipocytes derived from human BAT, NR enhanced in vitro norepinephrine-stimulated mitochondrial uncoupling. However, NR supplementation in human volunteers did not alter BAT activity or cold-induced thermogenesis. CONCLUSIONS NR stimulates in vitro human BAT but not in vivo BAT in humans. Our research demonstrates the need for further translational research to better understand the differences in NAD+ metabolism in mouse and human.
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Unusual Early Recovery of a Critical COVID-19 Patient After Administration of Intravenous Vitamin C.
Waqas Khan, HM, Parikh, N, Megala, SM, Predeteanu, GS
The American journal of case reports. 2020;21:e925521
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Coronavirus disease (Covid-19) continues to spread globally and to date there are no proven treatments. Current treatment focuses on the management of the associated acute respiratory distress syndrome (ARDS). There are many studies demonstrating that in severe sepsis and ARDS; Vitamin C reduces systemic inflammation, prevents lung damage, reduces the duration of mechanical ventilation (MV) and the length of intensive care unit (ICU) stay in patients. This is a case report where a critically ill patient received high-dose Vitamin C intravenous (IV) infusions and recovered. A 74 year-old woman with Covid-19, developed ARDS and septic shock. Usual medications were given. She needed MV and deteriorated rapidly. On Day 7 she was administered Vitamin C (11g per 24 hours as a continuous IV infusion). Her clinical condition improved slowly after this. In this case, high dose IV Vitamin C was associated with fewer days on mechanical intervention, a shorter ICU stay and earlier recovery. These results show the importance of further investigation of IV Vitamin C to assess its efficacy in critically ill Covid-19 patients requiring mechanical ventilation and ICU care.
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) continues to spread, with confirmed cases now in more than 200 countries. Thus far there are no proven therapeutic options to treat COVID-19. We report a case of COVID-19 with acute respiratory distress syndrome who was treated with high-dose vitamin C infusion and was the first case to have early recovery from the disease at our institute. CASE REPORT A 74-year-old woman with no recent sick contacts or travel history presented with fever, cough, and shortness of breath. Her vital signs were normal except for oxygen saturation of 87% and bilateral rhonchi on lung auscultation. Chest radiography revealed air space opacity in the right upper lobe, suspicious for pneumonia. A nasopharyngeal swab for severe acute respiratory syndrome coronavirus-2 came back positive while the patient was in the airborne-isolation unit. Laboratory data showed lymphopenia and elevated lactate dehydrogenase, ferritin, and interleukin-6. The patient was initially started on oral hydroxychloroquine and azithromycin. On day 6, she developed ARDS and septic shock, for which mechanical ventilation and pressor support were started, along with infusion of high-dose intravenous vitamin C. The patient improved clinically and was able to be taken off mechanical ventilation within 5 days. CONCLUSIONS This report highlights the potential benefits of high-dose intravenous vitamin C in critically ill COVID-19 patients in terms of rapid recovery and shortened length of mechanical ventilation and ICU stay. Further studies will elaborate on the efficacy of intravenous vitamin C in critically ill COVID-19.