Low-Dose Niacin Supplementation Improves Motor Function in US Veterans with Parkinson's Disease: A Single-Center, Randomized, Placebo-Controlled Trial.
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ABSTRACT:
SUBMITTER: Wakade C
PROVIDER: S-EPMC8698595 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundInfantile beriberi-related mortality is still common in South and Southeast Asia. Interventions to increase maternal thiamine intakes, and thus human milk thiamine, are warranted; however, the required dose remains unknown.ObjectivesWe sought to estimate the dose at which additional maternal intake of oral thiamine no longer meaningfully increased milk thiamine concentrations in infants at 24 wk postpartum, and to investigate the impact of 4 thiamine supplementation doses on milk and blood thiamine status biomarkers.MethodsIn this double-blind, 4-parallel arm randomized controlled dose-response trial, healthy mothers were recruited in Kampong Thom, Cambodia. At 2 wk postpartum, women were randomly assigned to consume 1 capsule, containing 0, 1.2 (estimated average requirement), 2.4, or 10 mg of thiamine daily from 2 through 24 weeks postpartum. Human milk total thiamine concentrations were measured using HPLC. An Emax curve was plotted, which was estimated using a nonlinear least squares model in an intention-to-treat analysis. Linear mixed-effects models were used to test for differences between treatment groups. Maternal and infant blood thiamine biomarkers were also assessed.ResultsIn total, each of 335 women was randomly assigned to1 of the following thiamine-dose groups: placebo (n = 83), 1.2 mg (n = 86), 2.4 mg (n = 81), and 10 mg (n = 85). The estimated dose required to reach 90% of the maximum average total thiamine concentration in human milk (191 µg/L) is 2.35 (95% CI: 0.58, 7.01) mg/d. The mean ± SD milk thiamine concentrations were significantly higher in all intervention groups (183 ± 91, 190 ± 105, and 206 ± 89 µg/L for 1.2, 2.4, and 10 mg, respectively) compared with the placebo group (153 ± 85 µg/L; P < 0.0001) and did not significantly differ from each other.ConclusionsA supplemental thiamine dose of 2.35 mg/d was required to achieve a milk total thiamine concentration of 191 µg/L. However, 1.2 mg/d for 22 wk was sufficient to increase milk thiamine concentrations to similar levels achieved by higher supplementation doses (2.4 and 10 mg/d), and comparable to those of healthy mothers in regions without beriberi. This trial was registered at clinicaltrials.gov as NCT03616288.
| S-EPMC8246599 | biostudies-literature
Project description:BackgroundCreatine synthesis from guanidinoacetate consumes ~50% of s-adenosylmethionine (SAM)-derived methyl groups, accounting for an equivalent proportion of s-adenosylhomocysteine (SAH) and total homocysteine (tHcys) synthesis. Dietary creatine inhibits the synthesis of guanidinoacetate, thereby lowering plasma tHcys in rats.ObjectiveWe tested the hypotheses that creatine supplementation lowers plasma guanidinoacetate, increases blood SAM, lowers blood SAH, and lowers plasma tHcys.MethodsBangladeshi adults were randomly assigned to receive 1 of 4 treatments for 12 wk: placebo (n = 101), 3 g/d creatine (Cr; n = 101), 400 μg/d folic acid (FA; n = 153), or 3 g/d creatine plus 400 μg/d folic acid (Cr+FA; n = 103). The outcomes of plasma guanidinoacetate and tHcys, as well as whole blood SAM and SAH, were analyzed at baseline and week 12 by HPLC. Treatment effects of creatine supplementation were examined with the use of the group comparisons of Cr vs. placebo and Cr+FA vs. FA.ResultsPlasma guanidinoacetate declined by 10.6% (95% CI: 4.9, 15.9) in the Cr group while increasing nonsignificantly in the placebo group (3.7%; 95% CI: -0.8, 8.5) (Pgroup difference = 0.0002). Similarly, plasma guanidinoacetate declined by 9.0% (95% CI: 3.4, 14.2) in the Cr+FA group while increasing in the FA group (7.0%; 95% CI: 2.0, 12.2) (Pgroup difference < 0.0001). Plasma tHcys declined by 23.4% (95% CI: 19.5, 27.1) and 21.0% (95% CI: 16.4, 25.2) in the FA and Cr+FA groups, respectively (Pgroup difference = 0.41), with no significant changes in the placebo or Cr groups (Pgroup difference = 0.35). A decrease in guanidinoacetate over time was associated with a decrease in tHcys over time in the Cr+FA group (β = 0.30; 95% CI: 0.17, 0.43; P < 0.0001).ConclusionsOur findings indicate that whereas creatine supplementation downregulates endogenous creatine synthesis, this may not on average lower plasma tHcys in humans. However, tHcys did decrease in those participants who experienced a decline in plasma guanidinoacetate while receiving creatine plus folic acid supplementation. This trial was registered at clinicaltrials.gov as NCT01050556.
| S-EPMC4580963 | biostudies-literature
Project description:We previously reported that individuals with Parkinson's disease (PD) present with lower vitamin B3 levels compared to controls. It may be related to carbidopa interaction, defective tryptophan metabolism, and stresses of night sleep disorder. Vitamin B3 is the energy source for all cells by producing NAD+ and NADP+ in redox reactions of oxidative phosphorylation. Thus, some symptoms of PD such as fatigue, sleep dysfunction, and mood changes may be related to the deficiency of vitamin B3. Here, we conducted an effectiveness trial to determine the effect of 12 months of low-dose niacin (a vitamin B3 derivative) enhancement in PD individuals. An average of 9 ± 6-point improvement in the Unified Parkinson's Disease Rating Scale (UPDRS) III (motor) score was observed after 12 months of daily niacin compared to the expected decline in score (effect size = 0.78, 95% CI = 7-11). Additionally, secondary outcome measures improved. Notably, handwriting size increased, fatigue perception decreased, mood improved, frontal beta rhythm during quiet stance increased, and stance postural sway amplitude and range of acceleration decreased. Set shifting, however, as measured by the Trail Making-B test, worsened from 66 to 96 s. Other measures did not change after 12 months, but it is not clear whether this represents a positive benefit of the vitamin. For example, while the quality of night sleep remained the same, there was a trend towards a decrease in the frequency of awakening episodes. These results suggest that niacin enhancement has the potential to maintain or improve quality of life in PD and slow disease progression.
| S-EPMC8245760 | biostudies-literature
Project description:BackgroundNiacin has multiple lipoprotein effects that may provide cardiovascular benefit when added to statin monotherapy.MethodsIn this randomized, placebo-controlled trial (n = 75) of magnetic resonance imaging of carotid atherosclerosis, we performed a secondary comparison of combination niacin-statin (simvastatin 20 mg/Niacin-ER 2G [S20/N]) to monotherapy with moderate (20 mg [S20]) and high-dose (80 mg [S80]) simvastatin on lipids, apolipoproteins (apo), low density lipoprotein (LDL) and high density lipoprotein (HDL) particle subclasses, and inflammatory markers.ResultsAt baseline, average age was 71, 72% were male, 62.5% used statins, and average LDL-cholesterol was 111 mg/dL. At 12 months, S20/N, compared to S80, significantly reduced apoB (-36.6% vs -11.9%; P = .05) and lipoprotein(a) (-18% vs +3.5%; P = .001) and had at least an equivalent effect on LDL-cholesterol (-39.3% vs -24.3%; P = .24). The combination reduced the proportion of subjects with atherogenic LDL pattern-B (50% to 11.5%) compared to S80 (56% to 56%) (P = .01). Despite increases in plasma free fatty acids (+62.4%; F = 5.65, P = .005 vs S20 and S80), plasma triglycerides (-29.4%; F = 6.88, P = .002 vs S20 and S80), and very-low-density lipoprotein (-44.2%; F = 7.94, P < .001 vs S20 and S80), levels were reduced by S20/N. S20/N increased HDL-cholesterol levels (+18.1%) as compared to S20 (0%) and S80 (+5.9%) (P < .001 vs both statin arms), largely due to an increase in HDL particle size (+4.6%; P = .01 vs both statin arms).ConclusionsWe demonstrate that full-dose niacin/moderate-dose simvastatin combination has sustained benefits on atherogenic apoB lipoproteins, at least comparable to high-dose simvastatin, while also raising HDL-cholesterol. Results of large clinical trials will inform whether niacin-statin combinations reduce cardiovascular disease events.
| S-EPMC3088112 | biostudies-literature
Project description:An experiment was conducted to investigate the effect of niacin supplementation on hepatic lipid metabolism in rabbits. Rex Rabbits (90 d, n = 32) were allocated to two equal treatment groups: Fed basal diet (control) or fed basal diet with additional 200 mg/kg niacin supplementation (niacin). The results show that niacin significantly increased the levels of plasma adiponectin, hepatic apoprotein B and hepatic leptin receptors mRNA (p<0.05), but significantly decreased the hepatic fatty acid synthase activity and adiponectin receptor 2, insulin receptor and acetyl-CoA carboxylase mRNA levels (p<0.05). Plasma insulin had a decreasing tendency in the niacin treatment group compared with control (p = 0.067). Plasma very low density lipoproteins, leptin levels and the hepatic adiponectin receptor 1 and carnitine palmitoyl transferase 1 genes expression were not significantly altered with niacin addition to the diet (p>0.05). However, niacin treatment significantly inhibited the hepatocytes lipid accumulation compared with the control group (p<0.05). In conclusion, niacin treatment can decrease hepatic fatty acids synthesis, but does not alter fatty acids oxidation and triacylglycerol export. And this whole process attenuates lipid accumulation in liver. Besides, the hormones of insulin, leptin and adiponectin are associated with the regulation of niacin in hepatic lipid metabolism in rabbits.
| S-EPMC5088423 | biostudies-literature
Project description:We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain.The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning.
| S-EPMC3566631 | biostudies-literature
Project description:PurposeThe purpose of this study was to examine whether long-term ingestion of low-dose milk protein supplementation causes a greater increase in muscle mass and strength of older adults during low-to-moderate intensity exercise training intervention than isocaloric carbohydrate.MethodsIn a randomized, double-blind, and placebo-controlled design, 122 healthy older adults (60-84 year) received either an acidified milk protein drink containing 10 g of milk protein (MILK; n = 61) or an isocaloric placebo drink (PLA; n = 61) daily throughout 6 months of body weight and medicine ball exercise training. Measurements before and after the intervention included body composition, physical performance and blood biochemistry.ResultsLean body mass significantly increased in the MILK group (+ 0.54 kg, p < 0.001), but did not change in the PLA group (- 0.10 kg, p = 0.534). The increases in the MILK group were significantly greater than in the PLA group (p = 0.004). Fat mass (- 0.77 kg) and plasma uric acid levels (- 0.3 mg/dL) significantly decreased only in the MILK group (p < 0.001), with a significant group difference (p = 0.002 and p < 0.001, respectively). Most of the physical performance tests significantly improved in both groups, but no group differences were found.ConclusionWe conclude that low-dose milk protein supplementation (10 g of protein/day) combined with low-to-moderate intensity exercise training is associated with increased muscle mass, but not improved physical performance compared to carbohydrate combined with exercise in healthy older adults. This study was registered in the UMIN Clinical Trials Registry (UMIN000032189).
| S-EPMC7900046 | biostudies-literature
Project description:Several methods of treatment for hepatocellular carcinoma (HCC) are often used in combination for either palliation or cure. We established a multidisciplinary treatment team (MDTT) at the San Francisco Veterans Affairs Medical Center in November 2003 and assessed whether aggressive multimodality treatment strategies may affect survival. A prospective database was established and follow-up information from patients with presumed HCC was collected up to November 2006. Information from the American College of Surgeons (ACS) cancer registry from January 2000 to November 2003 identified patients with HCC that were evaluated at the same institution prior to the establishment of the MDTT. The establishment of a MDTT resulted in the doubling of patient referrals for treatment. Significantly more patients were evaluated at earlier stages of disease and received either palliative or curative therapies. The overall survival (p<0.0001) and length of follow-up (p<0.05) were significantly improved after the establishment of the MDTT. Stage-by-stage comparisons indicate that aggressive multimodality therapy conferred significant survival advantage to patients with American Joint Commission on Cancer (AJCC) stage II HCC (odds ratio 15.50, p<0.001). Multidisciplinary collaboration and multimodality treatment approaches are important in the management of hepatocellular carcinoma and improves patient survival.
| S-EPMC2597312 | biostudies-other
Project description:Background: Motor learning is impaired in Parkinson's disease (PD), with patients demonstrating deficits in skill acquisition (online learning) and consolidation (offline learning) compared to healthy adults of similar age. Recent studies in young adults suggest that single bouts of aerobic exercise (AEX), performed in close temporal proximity to practicing a new motor task, may facilitate motor skill learning. Thus, we aimed at investigating the effects of a single bout of aerobic cycling on online and offline learning in PD patients. Methods: 17 PD patients (Hoehn and Yahr 1 - 2.5, age: 64.4 ± 6.2) participated in this crossover study. Immediately prior to practicing a novel balance task, patients either performed 30 min of (i) moderate intensity (60-70% VO2max) aerobic cycling, or (ii) seated rest (order counterbalanced). The task required patients to stabilize a balance platform (stabilometer) in a horizontal position for 30 s. For each experimental condition, patients performed 15 acquisition trials, followed by a retention test 24 h later. We calculated time in balance (platform within ± 5° from horizontal) for each trial, and analyzed within- and between-subjects differences in skill acquisition (online learning) and skill retention (offline learning) using mixed repeated-measures ANOVA. Results: We found that the exercise bout had no effect on performance level or online gains during acquisition, despite affecting the time course of skill improvements (larger initial and reduced late skill gains). Aerobic cycling significantly improved offline learning, as reflected by larger 24-h skill retention compared to the rest condition. Conclusion: Our results suggest that a single bout of moderate-intensity AEX is effective in improving motor skill consolidation in PD patients. Thus, acute exercise may represent an effective strategy to enhance motor memory formation in this population. More work is necessary to understand the underlying mechanisms, the optimal scheduling of exercise, and the applicability to other motor tasks. Further, the potential for patients in later disease stages need to be investigated. The study was a priori registered at ClinicalTrials.gov (NCT03245216).
| S-EPMC6204491 | biostudies-literature
Project description:This study tested the efficacy of repeated intravenous ketamine doses to reduce symptoms of posttraumatic stress disorder (PTSD). Veterans and service members with PTSD (n = 158) who failed previous antidepressant treatment were randomized to 8 infusions administered twice weekly of intravenous placebo (n = 54), low dose (0.2 mg/kg; n = 53) or standard dose (0.5 mg/kg; n = 51) ketamine. Participants were assessed at baseline, during treatment, and for 4 weeks after their last infusion. Primary analyses used mixed effects models. The primary outcome measure was the self-report PTSD Checklist for DSM-5 (PCL-5), and secondary outcome measures were the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Montgomery Åsberg Depression Rating Scale (MADRS). There were no significant group-by-time interactions for PTSD symptoms measured by the PCL-5 or CAPS-5. The standard ketamine dose ameliorated depression measured by the MADRS significantly more than placebo. Ketamine produced dose-related dissociative and psychotomimetic effects, which returned to baseline within 2 h and were less pronounced with repeated administration. There was no evidence of differential treatment discontinuation by ketamine dose, consistent with good tolerability. This clinical trial failed to find a significant dose-related effect of ketamine on PTSD symptoms. Secondary analyses suggested that the standard dose exerted rapid antidepressant effects. Further studies are needed to determine the role of ketamine in PTSD treatment. ClinicalTrials.gov identifier: NCT02655692.
| S-EPMC8767037 | biostudies-literature