Mid-term functional and quality of life outcomes of robotic and laparoscopic ventral mesh rectopexy: multicenter comparative matched-pair analyses.

BACKGROUND: The aim of this study was to compare patients' mid-term functional and quality of life (QoL) outcomes following robotic ventral mesh rectopexy (RVMR) and laparoscopic ventral mesh rectopexy (LVMR). METHODS: The data of consecutive female patients who underwent minimally invasive ventral mesh rectopexy for external or symptomatic internal rectal prolapse at 3 hospitals in Finland between January 2011 and December 2016 were retrospectively collected. Patients were matched by age and diagnosis at a 1:1 ratio. A disease-related symptom questionnaire was sent to all living patients at follow-up in July 2018. RESULTS: After a total of 401 patients (RVMR, n = 187; LVMR, n = 214) were matched, 152 patients in each group were included in the final analyses. The median follow-up times were 3.3 (range 1.6-7.4) years and 3.0 (range 1.6-7.6) years for the RVMR and LVMR groups, respectively. The postoperative QoL measures did not differ between the groups. Compared with the LVMR group, the RVMR group had lower postoperative Wexner Incontinence Score (median 5 vs. median 8; p < 0.001), experienced significant ongoing incontinence symptoms less often (30.6% vs. 49.0%; p < 0.001) and reported less postoperative faecal incontinence discomfort evaluated with the visual analogue scale (median 11 vs. median 39; p = 0.005). RVMR patients had a shorter hospital stay (2.2 days vs. 3.8 days; p < 0.001) but experienced more frequent de novo pelvic pain (31.8% vs. 11.8%; p < 0.001). CONCLUSION: RVMR and LVMR patients had equal functional and QoL outcomes. Those who underwent RVMR had lower mid-term anal incontinence symptom scores but suffered more frequent de novo pelvic pain.

Redo ventral rectopexy: is it worthwhile?

BACKGROUND: Minimally invasive ventral mesh rectopexy (VMR) is a widely used surgical treatment for posterior pelvic organ prolapse; however, evidence of the utility of revisional surgery is lacking. Our aim was to assess the technical details, safety and outcomes of redo minimally invasive VMR for patients with external rectal prolapse (ERP) recurrence or relapsed symptoms of internal rectal prolapse (IRP). METHODS: This is a retrospective cohort study of patients with recurrent ERP or symptomatic IRP who underwent redo minimally invasive VMR between 2011 and 2016. The study was conducted at three hospitals in Finland. Data collected retrospectively included patient demographics, in addition to perioperative and short-term postoperative findings. At follow-up, all living patients were sent a questionnaire concerning postoperative disease-related symptoms and quality of life. RESULTS: A total of 43 redo minimally invasive VMR were performed during the study period. The indication for reoperation was recurrent ERP in 22 patients and relapsed symptoms of IRP in 21 patients. In most operations (62.8%), the previously used mesh was left in situ and a new one was placed. Ten (23.3%) patients experienced complications, including 2 (4.7%) mesh-related complications. The recurrence rate was 4.5% for ERP. Three patients out of 43 were reoperated on for various reasons. One patient required postoperative laparoscopic hematoma evacuation. Patients operated on for recurrent ERP seemed to benefit more from the reoperation. CONCLUSIONS: Minimally invasive redo VMR appears to be a safe and effective procedure for treating posterior pelvic floor dysfunction with acceptable recurrence and reoperation rates.

Restored pelvic anatomy is preserved after laparoscopic and robot-assisted ventral rectopexy: MRI-based 5-year follow-up of a randomized controlled trial.

AIM: Our aim was to compare the long-term anatomical outcomes between robot-assisted ventral mesh rectopexy (RVMR) and laparoscopic ventral mesh rectopexy (LVMR) for external or internal rectal prolapse. METHOD: This study is a follow-up of a single-centre randomized controlled trial (RCT). Thirty patients were randomly allocated to RVMR (n = 16) or LVMR (n = 14). The primary end-point was maintenance of the restored pelvic anatomy 5 years after the operation, as assessed by magnetic resonance (MR) defaecography. Secondary outcome measures included the Pelvic Organ Prolapse Quantification (POP-Q) measures and functional results assessed using symptom questionnaires. RESULTS: Twenty-six patients (14 RVMR and 12 LVMR) completed the 5-year follow-up and were included in the study. The MRI results, POP-Q measurements and symptom-specific quality of life measures did not differ between the RVMR and LVMR groups. The MRI measurements of the total study population remained unchanged between 3 months and 5 years. In the Pelvic Floor Distress Inventory (PFDI-20), the RVMR group had lower symptom scores (mean 96.0, SD 70.7) than the LVMR group (mean 160.6, SD 58.9; P = 0.004). In the subscales of pelvic organ prolapse (POPDI-6) (mean 23.2, SD 24.3 vs mean 52.4, SD 22.4; P = 0.001) and the Colorectal-Anal Distress Inventory (CRADI-8) (mean 38.4, SD 23.3 vs mean 58.6, SD 25.4; P = 0.009), the patients in the RVMR group had significantly better outcomes. CONCLUSION: After VMR, the corrected anatomy was preserved. There were no clinically significant differences in anatomical results between the RVMR and LVMR procedures 5 years after surgery based on MR defaecography. However, functional outcomes were better after RMVR.

Cost-analysis and quality of life after laparoscopic and robotic ventral mesh rectopexy for posterior compartment prolapse: a randomized trial.

BACKGROUND: The aim of this study was to assess, whether robotic-assistance in ventral mesh rectopexy adds benefit to laparoscopy in terms of health-related quality of life (HRQoL), cost-effectiveness and anatomical and functional outcome. METHODS: A prospective randomized study was conducted on patients who underwent robot-assisted ventral mesh rectopexy (RVMR) or laparoscopic ventral mesh rectopexy (LVMR) for internal or external rectal prolapse at Oulu University Hospital, Finland, recruited in February-May 2012. The primary outcomes were health care costs from the hospital perspective and HRQoL measured by the 15D-instrument. Secondary outcomes included anatomical outcome assessed by pelvic organ prolapse quantification method and functional outcome by symptom questionnaires at 24 months follow-up. RESULTS: There were 30 females (mean age 62.5 years, SD 11.2), 16 in the RVMR group and 14 in the LVMR group. The surgery-related costs of the RVMR were 1.5 times higher than the cost of the LVMR. At 3 months the changes in HRQoL were 'much better' (RVMR) and 'slightly better' (LVMR) but declined in both groups at 2 years (RVMR vs. LVMR, p > 0.05). The cost-effectiveness was poor at 2 years for both techniques, but if the outcomes were assumed to last for 5 years, it improved significantly. The incremental cost-effectiveness ratio for the RVMR compared to LVMR was €39,982/quality-adjusted life years (QALYs) at 2 years and improved to €16,707/QALYs at 5 years. Posterior wall anatomy was restored similarly in both groups. The subjective satisfaction rate was 87% in the RVMR group and 69% in the LVMR group (p = 0.83). CONCLUSIONS: Although more expensive than LVMR in the short term, RVMR is cost-effective in long-term. The minimally invasive VMR improves pelvic floor function, sexual function and restores posterior compartment anatomy. The effect on HRQoL is minor, with no differences between techniques.

A prospective pilot study on MRI visibility of iron oxide-impregnated polyvinylidene fluoride mesh after ventral rectopexy.

BACKGROUND: Magnetic resonance imaging (MRI) provides excellent information about pelvic anatomy after ventral rectopexy, but the position of the conventional mesh is not seen constantly. Iron oxide-impregnated polyvinylidene fluoride (PVDF) meshes are proven to have MRI visibility in hernia or vaginal reconstructive surgery. This prospective pilot study was designed to assess the visualization, position, and shape of the magnetic resonance (MR)-visible synthetic pelvic mesh used in minimally invasive ventral rectopexy. METHODS: Eight patients with pelvic organ prolapse were recruited for laparoscopic (LVMR) or robotic-assisted ventral mesh rectopexy (RVMR) with a synthetic MR-visible PVDF mesh. A follow-up visit was scheduled at 3 months after surgery. MR imaging was performed to evaluate the position and dimensions of the mesh and anatomical result. The visibility of the mesh in each sequence was assessed subjectively. RESULTS: The visibility of the mesh was best on T1-weighted flash images. The mesh was also well visualized on T2-weighted sagittal images. T2-weighted images, in general, provided best visualization of the surrounding anatomical structures and enabled assessment of the mesh fixation. CONCLUSIONS: T2 sagittal and T1-weighted flash images provide the best information about the position and integrity of the iron oxide-impregnated PVDF mesh after LVMR or RVMR with a short examination time.

Robot-assisted vs laparoscopic ventral rectopexy for external or internal rectal prolapse and enterocele: a randomized controlled trial.

AIM: The purpose of this prospective randomized study was to compare robot-assisted and laparoscopic ventral rectopexy procedures for posterior compartment procidentia in terms of restoration of the anatomy using magnetic resonance (MR) defaecography. METHOD: Sixteen female patients (four with total prolapse, twelve with intussusception) underwent robot-assisted ventral mesh rectopexy (RVMR) and 14 female patients (two with prolapse, twelve with intussusception) laparoscopic ventral mesh rectopexy (LVMR). Primary outcome measures were perioperative parameters, complications and restoration of anatomy as assessed by MR defaecography, which was performed preoperatively and 3 months after surgery. RESULTS: Patient demographics, operation length, operating theatre times and length of in-hospital stay were similar between the groups. The anatomical defects of rectal prolapse, intussusception and rectocele and enterocele were similarly corrected after rectopexy in either technique as confirmed with dynamic MR defaecography. A slight residual intussusception was observed in three patients with primary total prolapse (two RVMR vs one LVMR) and in one patient with primary intussusception (RVMR) (P = 0.60). Rectocele was reduced from a mean of 33.0 ± 14.9 mm to 5.5 ± 8.4 mm after RVMR (P < 0.001) and from 24.7 ± 17.5 mm to 7.2 ± 3.2 mm after LVMR (P < 0.001) (RVMR vs LVMR, P = 0.10). CONCLUSION: Robot-assisted laparoscopic ventral rectopexy can be performed safely and within the same operative time as conventional laparoscopy. Minimally invasive ventral rectopexy allows good anatomical correction as assessed by MR defaecography, with no differences between the techniques.

Laparoscopic ventral rectopexy in male patients with external rectal prolapse is associated with a high reoperation rate.

BACKGROUND: Laparoscopic ventral rectopexy has been used to treat male patients with external rectal prolapse, but evidence to support this approach is scarce. The aim of this study was to evaluate the results of this new abdominal rectopexy surgical technique in men. METHODS: This was a retrospective multicenter study. Adult male patients who were operated on for external rectal prolapse using ventral rectopexy in five tertiary hospitals in Finland between 2006 and 2014 were included in the study. Patient demographics, detailed operative, postoperative and short-term follow-up data were collected from patient registers in participating hospitals. A questionnaire and informed consent form was sent to all patients. The questionnaire included scores for anal incontinence, obstructed defecation syndrome, urinary symptoms and sexual dysfunction. The main outcome measure was the incidence of recurrent rectal prolapse. Surgical morbidity, the need for surgical repair due to recurrent symptoms and functional outcomes were secondary outcome measures. RESULTS: A total of 52 adult male patients with symptoms caused by external rectal prolapse underwent ventral rectopexy. The questionnaire response rate was 64.4 %. Baseline clinical characteristics and perioperative results were similar in the responder and non-responder groups. A total of 9 (17.3 %) patients faced complications. There were two (3.8 %) serious surgical complications during the 30-day period after surgery that necessitated reoperation. None of the complications were mesh related. Recurrence of the prolapse was noticed in nine patients (17 %), and postoperative mucosal anal prolapse symptoms persisted in 11 patients (21 %). As a result, the reoperation rate was high. Altogether, 17 patients (33 %) underwent reoperation during the follow-up period due to postoperative complications or recurrent rectal or mucosal prolapse. According to the postoperative questionnaire data, patients under 40 had good functional results in terms of anal continence, defecation, urinary functions and sexual activity. CONCLUSIONS: Laparoscopic ventral rectopexy is a safe surgical procedure in male patients with external prolapse. However, a high overall reoperation rate was noticed due to recurrent rectal and residual mucosal prolapse. This suggests that the ventral rectopexy technique should be modified or combined with other abdominal or perineal methods when treating male rectal prolapse patients.

Robotic-assisted and laparoscopic ventral rectopexy in the treatment of rectal prolapse: a matched-pairs study of operative details and complications.

BACKGROUND: Laparoscopic ventral rectopexy has been proven to be safe and effective in the treatment of rectal prolapse or intussusception. Robotic-assisted surgery may offer potential benefits to this operation. This study describes the comparison of robotic-assisted and conventional laparoscopic ventral rectopexy in terms of clinical parameters, operative details, postoperative complications and short-term outcomes. METHODS: Twenty patients operated on for rectal prolapse or intussusception using the Da Vinci Surgical System (Intuitive Surgical Inc, Sunnyvale CA, USA) were prospectively followed for 3 months. The cases were pair-matched with laparoscopically operated controls from registry files. RESULTS: Mean operating time was 159 min (standard deviation; ±37 SD) and 153 min (±33 SD) and mean total time in the operating theatre 231 min (±39 SD) and 234 min (±41 SD) for robotic-assisted and laparoscopic operations, respectively. Mean blood loss was 25 ml (±49 SD) in robotic-assisted and 37 ml (±50 SD) in laparoscopic procedures. There was one (5 %) significant complication in each group. Mean length of hospital stay was 3.1 (±2 SD) and 3.3 (±1.3 SD) days for the robotic-assisted and laparoscopic groups, respectively. The subjective benefit rate was the same in both groups: 16/20 (80 %). One patient in the robotic-assisted group continued to have symptoms of obstructed defecation, and there was one recurrence of prolapse in the laparoscopic group. CONCLUSIONS: Robotic-assisted laparoscopic ventral rectopexy is safe, feasible and not more time consuming than the laparoscopic technique even at the beginning of the learning curve. The short-term results are comparable with those of laparoscopy. We found no arguments to support the routine use of robotic assistance in rectopexy operations.

Topologically-imposed vacancies and mobile solid 3He on carbon nanotube.

Low dimensional fermionic quantum systems are exceptionally interesting because they reveal distinctive physical phenomena, including among others, topologically protected excitations, edge states, frustration, and fractionalization. Our aim was to confine 3He on a suspended carbon nanotube to form 2-dimensional Fermi-system. Here we report our measurements of the mechanical resonance of the nanotube with adsorbed sub-monolayer down to 10 mK. At intermediate coverages we have observed the famous 1/3 commensurate solid. However, at larger monolayer densities we have observed a quantum phase transition from 1/3 solid to an unknown, soft, and mobile solid phase. We interpret this mobile solid phase as a bosonic commensurate crystal consisting of helium dimers with topologically-induced zero-point vacancies which are delocalized at low temperatures. We thus demonstrate that 3He on a nanotube merges both fermionic and bosonic phenomena, with a quantum phase transition between fermionic solid 1/3 phase and the observed bosonic dimer solid.

Cardiovascular risk factors in type 2 diabetic patients in Bulgaria.

UNLABELLED: Type 2 diabetes mellitus is associated with an excessively high morbidity and mortality from cardiovascular disease. Macrovascular disease with its complications is the leading cause of death in Bulgaria. AIM OF THIS STUDY: To examine cardiovascular risk factors in patients with type 2 diabetes. MATERIAL AND METHODS: The study included 556 patients with type 2 diabetes and 575 healthy subjects. All participants filled a questionnaire on medical history, lifestyle and family history and standardised measurements were taken of some of their anthropometric parameters and blood pressure. Venous blood was drawn after an overnight fast for the examination of glucose, lipids, C-reactive protein and other cardiovascular risk factors. RESULTS: Seventy-eight percent of the diabetic subjects had a history of coronary heart disease. The diabetics had significantly higher body mass index (27.1 +/- 4.4 kg/m2 vs. 25.0 +/- 3.8 kg/m2; mean +/- SD), waist circumference (101 +/- 10.2 vs. 87 +/- 8), systolic (131 +/- 12 mm Hg vs. 123 +/- 11) and diastolic blood pressure (85 +/- 9 mm Hg vs. 78 +/- 7), blood glucose (8.4 +/- 2.3 mmol/l vs. 5.4 +/- 0.7), total cholesterol (5.8 +/- 0.78 mmol/l vs. 4.9 +/- 1.0), triglycerides (2.18 +/- 1.02 mmol/l vs. 0.98 +/- 0.60) and C-reactive protein (5.2 +/- 3.9 vs. 3.7 +/- 3.1 mg/l) as well as significantly lower levels of HDL-cholesterol (0.96 +/- 0.28 mmol/l vs. 1.45 +/- 0.47) vs. controls. CONCLUSIONS: Our study demonstrates that patients with type 2 diabetes in Bulgaria have significantly increased levels of cardiovascular risk factors, which could explain the excessive cardiovascular mortality of these patients.

Long-term effects of vitamin E, vitamin C, and combined supplementation on urinary 7-hydro-8-oxo-2'-deoxyguanosine, serum cholesterol oxidation products, and oxidation resistance of lipids in nondepleted men.

We studied the long-term effects of vitamins E and C and their combination on lipid peroxidation in vivo and in vitro. The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) trial is a double-masked placebo-controlled randomized clinical trial to study the effects of vitamin C (500 mg of slow release ascorbate per day), vitamin E (182 mg of RRR-alpha-tocopherol acetate per day), and the combination of both antioxidants. Lipid peroxidation measurements were carried out for 48 male participants at entry and at 12 and 36 months. Compared with placebo, vitamin E and the vitamin combination increased plasma lipid-standardized alpha-tocopherol during the first 12 months by 68.2% and 65.2% (P:<0. 001 for both), respectively, and reduced serum 7beta-hydroxycholesterol by 50.4% (P:=0.013) and 44.0% (P:=0.041), respectively. The net change of lipid standardized alpha-tocopherol was 63.8% after 36 months of vitamin E supplementation and 43.3% for the combination. Vitamin C supplementation elevated plasma total ascorbate level by 30.1% (P:=0.043) in 12 months and by 91.1% (P:=0. 001) in 36 months. Neither vitamin E, vitamin C, nor the combination influenced the urinary excretion rate of 7-hydro-8-oxo-2'-deoxyguanosine or the antioxidative capacity of plasma. Vitamin E and the combination of vitamins E and C enhanced the oxidation resistance of isolated lipoproteins and total serum lipids. Our data indicate that long-term supplementation of nondepleted men with a reasonable dose of vitamin E alone or in combination with slow release vitamin C reduces lipid peroxidation in vitro and in vivo, whereas a relatively high dose of vitamin C alone does not.

Determinants of plasma coenzyme Q10 in humans.

In the present study, we assessed the strongest determinants of plasma coenzyme Q10 (Qm10) in 518 men and women (aged 45-70 years) with a stepwise multivariate regression model. Male gender (P<0.001), serum cholesterol (P<0.001), serum gamma-glutamyltransferase (P<0.001), serum triglycerides (P< 0.001), age (P=0.017) and 4-day alcohol consumption (P=0.03) were the most important factors which were directly associated with plasma Q10). The intensity of conditioning exercise (P=0.03) and use of statins (P<0.05) showed an inverse association with plasma Q10. None of the assessed nutrients increased plasma Q10 levels significantly. Our results suggest that many confounding factors, in addition to serum cholesterol and triglycerides, should be taken into account when the role of plasma Q10 is examined in epidemiological research.

Effect of oral coenzyme Q10 supplementation on the oxidation resistance of human VLDL+LDL fraction: absorption and antioxidative properties of oil and granule-based preparations.

Coenzyme Q10 (Q10) is supposed to be an important endogenous lipid-soluble antioxidant. We studied 60 healthy 46 +/- 7 (mean +/- SD)-year-old smoking men. They were randomized into three groups to receive oil-based or granular Q10 (90 mg/d) or placebo for 2 months. Oil-based capsule elevated Q10 in plasma by 178% and in VLDL+LDL fraction by 160%. The granular preparation increased Q10 in plasma by 168% and in VLDL+LDL by 127%. However, the 2-month Q10 supplementation did not increase the oxidation resistance of VLDL+LDL fraction, as assessed by copper induced VLDL+LDL oxidation, haemin+H(2)O(2)-induced VLDL+LDL oxidation, total antioxidative capacity of LDL, and plasma malondialdehyde measurements. The first and the last dose was used to carry out a 12 h pharmacokinetic study (five subjects per group), which indicated that only a small part of supplemented Q10 was absorbed to the circulation in 12 h and that the absorption varied extensively between subjects. Our results suggest that at least among smoking men, 90 mg of orally supplemented Q10 daily does not increase the oxidation resistance of VLDL+LDL. Bioavailability of both the granular and the oil-based Q10 preparation was similar during the long-term supplementation, but one dose of 30 mg had only a marginal effect on the plasma levels of Q10.

A randomized, single-blind, placebo-controlled trial of the effects of 200 mg alpha-tocopherol on the oxidation resistance of atherogenic lipoproteins.

Supplementation with high doses of alpha-tocopherol has increased the oxidation resistance of LDL in many clinical trials. There have been only a few placebo-controlled trials in healthy persons of alpha-tocopherol doses usually contained in dietary supplements. We carried out a single-blind, placebo-controlled, randomized trial to examine the effect of 200 mg RRR-alpha-tocopheryl acetate/d on the oxidation resistance of atherogenic lipoproteins (VLDL+LDL including intermediate-density lipoproteins) in 40 smoking men. VLDL+LDL oxidation resistance was assessed as conjugated dienes after copper induction and hemin degradation after hydrogen peroxide induction. Also, the LDL total peroxyl-radical trapping antioxidant parameter (LDL TRAP) and plasma malondialdehyde were measured at baseline and after 2 mo of supplementation. Plasma RRR-alpha-tocopherol concentrations were measured at 2-h intervals for 12 h at baseline and after 2 mo of supplementation. Compared with placebo, 200-mg RRR-alpha-tocopheryl acetate supplementation elevated plasma and VLDL+LDL alpha-tocopherol concentrations, LDL TRAP, and oxidation resistance of VLDL+LDL. Plasma alpha-tocopherol increased by 88% (P < 0.0001), VLDL+LDL alpha-tocopherol increased by 90% (P < 0.0001), and LDL TRAP by 58% (P < 0.0001). The time to the start of oxidation (lag time) was prolonged by 34% when assessed with a copper-induced method and by 109% when assessed with a hemin + hydrogen peroxide-induced method; the time to maximal oxidation was prolonged by 21% (copper-induced method) in the vitamin E-supplemented group. Changes in plasma alpha-tocopherol, lipid-standardized alpha-tocopherol, and VLDL+LDL alpha-tocopherol correlated significantly with changes in LDL TRAP, lag time, and time to maximal oxidation. Differences in changes between groups in the area under the curve for plasma alpha-tocopherol were significant (P < 0.009). Our results suggest that 200 mg oral RRR-alpha-tocopheryl acetate/d had a clear effect on the in vitro oxidation of VLDL+LDL in smoking men.

Ascorbate and urate are the strongest determinants of plasma antioxidative capacity and serum lipid resistance to oxidation in Finnish men.

Copper-induced plasma lipoprotein oxidation resistance has usually been determined in separated low density lipoprotein (LDL) fractions, that do not contain water-soluble antioxidants present in blood plasma. The aim of this study was to find the main determinants of the measurements of copper-induced lipid oxidation resistance (lag time) in whole serum and plasma total peroxyl radical trapping capacity (TRAP) in a population sample of smoking (n = 25) or non-smoking (n = 26) middle aged men at high risk of cardiovascular diseases. Smokers had significantly lower plasma ascorbic acid values, but only slightly lower alpha-tocopherol, beta-carotene and serum urate values than non-smokers. Plasma ascorbic acid concentration explained 23.5% of the lag time variation (standardized regression coefficient beta = 0.48; P = 0.004) in smokers and 5.6% in non-smokers. Serum urate concentration was the strongest determinant of lag time in non-smokers (beta = 0.64, P < 0.001). In addition, serum albumin, lipid standardized alpha-tocopherol and serum high density lipoprotein (HDL) cholesterol entered the multivariate regression mode for lag time. For plasma TRAP, only urate and ascorbic acid entered the multivariate regression model. Lag times in serum and in isolated very low density lipoprotein (VLDL) and LDL fraction did not correlate, but the maximal rate of these reactions correlated significantly. These results confirm that lipid peroxidation resistance in serum or plasma are associated with ascorbic acid, urate, alpha-tocopherol, albumin and HDL concentrations. The measurement of lipid oxidation resistance in whole serum might be more physiological than in isolated lipoprotein fraction, as the effects of water-soluble antioxidants are not artificially removed.

Effect of combined coenzyme Q10 and d-alpha-tocopheryl acetate supplementation on exercise-induced lipid peroxidation and muscular damage: a placebo-controlled double-blind study in marathon runners.

To test the effects of combined coenzyme Q10 (Q10) and d-alpha-tocopheryl acetate supplementation on exercise-induced oxidative stress and muscular damage we conducted a double-blind study in 37 moderately trained male marathon runners. These were randomly allocated to receive either an antioxidant cocktail: 90 mg of Q10 and 13.5 mg of d-alpha-tocopheryl acetate daily (18 men) or placebo (19 men) for three weeks before a marathon (42km) run. Just before the run, plasma Q10 was 282% (p < 0.0001) and plasma vitamin E 16% (p < 0.007) higher in the supplemented group, than in the placebo group. Also the proportion of plasma ubiquinol of total Q10, an indication of plasma redox status in vivo, was significantly higher in the supplemented group. Furthermore, the susceptibility of the VLDL + LDL fraction, to copper-induced oxidation, was significantly reduced in the supplemented group, compared to the placebo group. The exercise increased lipid peroxidation significantly in both study groups, as assessed by the elevated proportion LDL of LDL and the increased susceptibility of lipoproteins to copper induced oxidation. However, the supplementation had no effect on lipid peroxidation or on the muscular damage (increase in serum creatine kinase activity or in plasma lactate levels) induced by exhaustive exercise. Plasma ascorbate, Q10, whole blood glutathione and serum uric acid concentrations increased during the exercise, elevating significantly the TRAP value of plasma by 10.3% and the proportion of plasma ubiquinol of total Q10 by 4.9%. These results suggest that even though exercise increases plasma lipid peroxidation, it also elevates the antioxidative capacity of plasma, as assessed by the increased plasma TRAP and the proportion of Q10H2 of total Q10. However, prior supplementation with small doses of Q10 and d-alpha-tocopheryl acetate neither attenuates the oxidation of lipoproteins nor muscular damage induced by exhaustive exercise such as encountered in a marathon run.

Antioxidative efficacy of parallel and combined supplementation with coenzyme Q10 and d-alpha-tocopherol in mildly hypercholesterolemic subjects: a randomized placebo-controlled clinical study.

It has been claimed that coenzyme Q10 (Q10) would be an effective plasma antioxidant since it can regenerate plasma vitamin E. To test separate effects and interaction between Q10 and vitamin E in the change of plasma concentrations and in the antioxidative efficiency, we carried out a double-masked, double-blind clinical trial in 40 subjects with mild hypercholesterolemia undergoing statin treatment. Subjects were randomly allocated to parallel groups to receive either Q10 (200 mg daily), d-alpha-tocopherol (700 mg daily), both antioxidants or placebo for 3 months. In addition we investigated the pharmacokinetics of Q10 in a separate one-week substudy. In the group that received both antioxidants, the increase in plasma Q10 concentration was attenuated. Only vitamin E supplementation increased significantly the oxidation resistance of isolated LDL. Simultaneous Q10 supplementation did not increase this antioxidative effect of vitamin E. Q10 supplementation increased and vitamin E decreased significantly the proportion of ubiquinol of total Q10, an indication of plasma redox status in vivo. The supplementations used did not affect the redox status of plasma ascorbic acid. In conclusion, only vitamin E has antioxidative efficiency at high radical flux ex vivo. Attenuation of the proportion of plasma ubiquinol of total Q10 in the vitamin E group may represent in vivo evidence of the Q10-based regeneration of the tocopheryl radicals. In addition, Q10 might attenuate plasma lipid peroxidation in vivo, since there was an increased proportion of plasma ubiquinol of total Q10.

Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men.

Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F2-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the "Antioxidant Supplementation in Atherosclerosis Prevention" (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of D-alpha-tocopheryl acetate daily), both vitamins (CellaVie), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F2-isoprostane concentration was lowered by 17.3% (95% CI 3.9-30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F2-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis.

Effect of supplementation of smoking men with plain or slow release ascorbic acid on lipoprotein oxidation.

OBJECTIVE: To study the effects of two month ascorbic acid supplementation on in vitro lipoprotein oxidation resistance and on in vivo lipid peroxidation, and to compare the absorption of two ascorbic acid preparations. DESIGN: Randomized, single blinded and placebo-controlled clinical trial. SETTING: Men, aged 36-65 y, smoking 11-40 cigarettes daily. SUBJECTS: Sixty-two subjects were recruited by newspaper advertisements and randomized. Fifty-nine subjects completed the study. INTERVENTION: Subjects were randomized into three groups to receive 250 mg BID of plain or slow release ascorbic acid tablets or placebo daily for two months. In the pharmacokinetic part of the study, the absorption of the ascorbic acid preparations was followed for 12 h. MAIN OUTCOME MEASURES: Plasma malondialdehyde (MDA) concentration and the oxidation resistance of VLDL + LDL. For the pharmacokinetic study, the area under the plasma concentration curve (AUC) of ascorbic acid. RESULTS: Plasma reduced ascorbic acid increased by 32% in the plain ascorbate group and by 54% in the slow release group during a two month supplementation. Plasma MDA increased in the plain ascorbic acid group compared with placebo group (P < 0.05), but there were no significant differences in the changes in lipoprotein oxidation reactions induced by copper or by hemin and H2O2. Plasma reduced and total ascorbic acid AUC values were significantly higher in both plain and slow release ascorbate groups compared with placebo group. CONCLUSIONS: Oral supplementation of 500 mg of ascorbic acid daily for two months alone without any other antioxidant does not appear to have protective effect on either in vitro lipoprotein oxidation resistance or in vivo lipid peroxidation in smoking men, but might even promote the formation of MDA.

Mercury-binding capacity of organic and inorganic selenium in rat blood and liver.

The mercury-binding capacity of seleno-DL-methionine and selenium dioxide was assessed in male Wistar rats. Mercury was supplied as fish loaves made of northern pike or rainbow trout. We used a selenium concentration of 3.4 mg/kg fish, about sixfold compared to the equivalent quantity of mercury. Seleno-DL-methionine had a tendency to increase both methyl mercury and total mercury in blood, although it also seemed to reduce the proportion of methyl mercury of total mercury. Selenium dioxide lowered mercury levels by 24-29% both in the blood and in the liver of rats that were fed with northern pike.