Standardized Extract of Valeriana officinalis Improves Overall Sleep Quality in Human Subjects with Sleep Complaints: A Randomized, Double-Blind, Placebo-Controlled, Clinical Study.

INTRODUCTION: Sleep deficit or poor sleep leads to ill-health, whereas sleep deprivation for longer periods of time increases the risk of developing adverse conditions associated with poor quality of life, and high socioeconomic impact. The treatments for sleep disturbances include melatonin and over-the-counter medicines like diphenhydramine and doxylamine, all of which have negative side effects. Valerian (Valeriana officinalis L.) is a traditional herb and the most preferred alternate sleep solution to manage sleep complaints. METHODS: Eighty adult subjects with sleep complaints were randomized in 1:1 ratio to receive either V. officinalis extract (VE) or placebo for 8 weeks in a double-blind, placebo-controlled, parallel, clinical study. Primary efficacy endpoints included the Pittsburgh Sleep Quality Index (PSQI) and sleep latency using wrist actigraphy (WA), as well as a number of secondary endpoints, including sleep parameters such as actual sleep time and sleep efficiency using WA, the Epworth Sleepiness Scale (ESS), the Beck Anxiety Inventory (BAI), the Visual Analogue Scale (VAS) for the feeling of waking up refreshed, and a tertiary endpoint of sleep parameters using polysomnography (PSG) in a subset of 20 subjects per group. Safety parameters included physical examination, vital sign measurements, hematology, and clinical chemistry tests. Adverse events and serious adverse events were monitored throughout the study period. RESULTS: Seventy-two subjects (35 and 37 subjects in the placebo and VE groups, respectively) completed the study and were included in the efficacy assessments. On Days 14, 28, and 56, the PSQI Total Score in the VE group decreased significantly (p < 0.05) compared to the placebo group. Further, the VE group showed significant improvements (p < 0.05) in sleep latency and actual sleep time on Days 3, 14, 28, and 56, and sleep efficiency on Days 14, 28, and 56, as evaluated by WA. There was a decrease (p < 0.05) in anxiety (BAI) on Days 14, 28, and 56, daytime drowsiness (ESS) on Days 28 and 56, and an increased feeling of waking up refreshed (VAS) on Days 28 and 56 compared to placebo. PSG results carried out in subset of subjects revealed significant improvements (p < 0.05) in total sleep time, sleep latency, and sleep efficiency on Day 56 in the VE group compared to the placebo group. No safety concerns were observed throughout the study. CONCLUSION: VE supplementation significantly improved various subjective and objective parameters of sleep in young subjects with mild insomnia symptoms, such as overall sleep quality, sleep latency, sleep efficiency, and total sleep time. We also observed decreased anxiety and daytime sleepiness, and improved feeling of being refreshed after waking up with VE supplementation. VE was found to be safe and well tolerated throughout the study. TRIAL REGISTRATION: Clinical Trials Registry of India: CTRI/2022/05/042818.

A proprietary black cumin oil extract (Nigella sativa) (BlaQmax®) modulates stress-sleep-immunity axis safely: Randomized double-blind placebo-controlled study.

Objective: Stress, sleep, and immunity are important interdependent factors that play critical roles in the maintenance of health. It has been established that stress can affect sleep, and the quality and duration of sleep significantly impact immunity. However, single drugs capable of targeting these factors are limited because of their multi-targeting mechanisms. The present study investigated the influence of a proprietary thymoquinone-rich black cumin oil extract (BCO-5) in modulating stress, sleep, and immunity. Methods: A randomized double-blinded placebo-controlled study was carried out on healthy volunteers with self-reported non-refreshing sleep issues (n = 72), followed by supplementation with BCO-5/placebo at 200 mg/day for 90 days. Validated questionnaires, PSQI and PSS, were employed for monitoring sleep and stress respectively, along with the measurement of cortisol and melatonin levels. Immunity markers were analyzed at the end of the study. Results: In the BCO-5 group, 70% of the participants reported satisfaction with their sleep pattern on day 7 and 79% on day 14. Additionally, both inter- and intra- group analyses of the total PSQI scores and component scores (sleep latency, duration, efficiency, quality, and daytime dysfunction) on days 45 and 90 showed the effectiveness of BCO-5 in the improvement of sleep (p < 0.05). PSS-14 analysis revealed a significant reduction in stress, upon both intra (p < 0.001) and inter-group (p < 0.001) comparisons. The observed reduction in stress among the BCO-5 group, with respect to the placebo, was significant with an effect size of 1.19 by the end of the study (p < 0.001). A significant correlation was also observed between improved sleep and reduced stress as evident from PSQI and PSS. Furthermore, there was a significant modulation in melatonin, cortisol, and orexin levels. Hematological/immunological parameters further revealed the immunomodulatory effects of BCO-5. Conclusion: BCO-5 significantly modulated the stress-sleep-immunity axis with no side effects and restored restful sleep.

Influence of CurQfen®-curcumin on cognitive impairment: a randomized, double-blinded, placebo-controlled, 3-arm, 3-sequence comparative study.

Background: Although curcumin is a blood-brain-barrier permeable molecule with the ability to bind and segregate ß-amyloid plaques and neurofibrillary tangles of hyperphosphorylated tau proteins, its poor oral bioavailability, rapid biotransformation to inactive metabolites, fast elimination from the systemic circulation, and hence the poor neuronal uptake has been limiting its clinical efficacy under neurodegenerative conditions. Objective: We hypothesized that the highly bioavailable CurQfen-curcumin (CGM), which has been shown to possess significant blood-brain-barrier permeability and brain bioavailability, would ameliorate dementia in neurodegenerative conditions. Methods: In the present double-blinded placebo-controlled 3-arm 3-sequence comparative study, 48 subjects characterized with moderate dementia due to the onset of Alzheimer's disease were randomized into three groups (N = 16/group) and supplemented with 400 mg × 2/day of either placebo (MCC), unformulated standard curcumin complex with 95% purity (USC), or CGM as a sachet for six months. The relative changes in cognitive and locomotor functions and biochemical markers were compared. Results: Supplementation with CGM produced significant (P < 0.05) improvement in the Mini-Mental State Examination (MMSE) and the Geriatric Locomotive Function Scale (GLFS) scores in both intra- and inter-group comparison by 2 × 2 repeated measures (RM) ANOVA. Further, analysis of the serum levels of specific biomarkers (BDNF, Aß42, tau protein, IL-6, and TNF-α) also revealed a significant (P < 0.05) improvement among CGM subjects as compared to placebo and the USC groups. Conclusion: Supplementation with CGM as sachet was found to offer significant delay in the progress of Alzheimer's disease, as evident from the improvements in locomotive and cognitive functions related to dementia. Clinical trial registration: http://ctri.nic.in, identifier: CTRI/2018/03/012410.

A phase I clinical trial to evaluate the safety of thymoquinone-rich black cumin oil (BlaQmax®) on healthy subjects: Randomized, double-blinded, placebo-controlled prospective study.

Black cumin or black seed (Nigella sativa L.) is a popular medicinal herb and culinary spice belonging to Ranunculacea family. Thymoquinone (TQ) is the major active phytoconstituent in black cumin and is abundant in the volatile oil fraction. Though black cumin oil containing low TQ content (less than 1%) has been clinically investigated, clinical efficacy and safety data of TQ-rich oil is limited. A recent study with black cumin oil formulation containing 5% TQ (BCO-5) exhibited significant clinical efficacy to alleviate sleep disorders and stress. So, the present phase 1 randomized, double-blinded, placebo-controlled trial evaluated the safety of BCO-5 at a dose of 200 mg/adult/day for 90 days on healthy subjects (n = 70). Both the biochemical and hematological parameters were analysed along with the adverse events or side effects to establish the clinical safety of BCO-5. The study reported neither serious adverse side effects nor any significant alterations in the hematological parameters. The absence of significant changes in the biochemical parameters related to liver function (ALT, AST, ALP), renal function (serum creatinine and urea) were also observed. However, analysis of lipid profile showed a significant (P < 0.05) reduction in total cholesterol, LDL, VLDL and triglycerides, but within the normal range. In conclusion, BCO-5 is safe at 200 mg/adult/day for human consumption and may be clinically evaluated for various health beneficial pharmacological activities where black cumin oil has been shown to have positive effects.

Influence of a low-dose supplementation of curcumagalactomannoside complex (CurQfen) in knee osteoarthritis: A randomized, open-labeled, active-controlled clinical trial.

A 6-week, randomized, open-label, active-controlled clinical trial was conducted to evaluate the influence of a low-dose curcumagalactomannosides (CGM) (400 mg once daily) in OA subjects. The treatment was compared with a standard combination of 500 mg glucosamine hydrochloride (GLN) and 415 mg chondroitin sulphate (CHN), supplied as a single oral dose twice a day. Out of 84 subjects randomized, 72 subjects who have completed the study were evaluated for the safety and efficacy of the treatments at baseline and subsequent visits (day 28 and 42), by measuring walking performance, VAS, KPS, and WOMAC scores. CGM exhibited 47.02, 21.43, and 206% improvement in VAS, KPS, and walking performance, respectively, compared to the baseline. Similarly, there was 31.17, 32.93, 36.44, and 35% improvement in the pain, stiffness, physical function, and total WOMAC scores. CGM also caused a substantial reduction in the serum inflammatory marker levels. The results indicate that a short-term supplementation of a low dosage CGM exerted superior beneficial effects than a high-dosage CHN-GLN combination in alleviating the pain and symptoms of OA subjects. Further clinical trials of extended duration in a larger population is required to substantiate the efficacy of CGM in the long-term management of OA.

A double blind, placebo-controlled randomized comparative study on the efficacy of phytosterol-enriched and conventional saw palmetto oil in mitigating benign prostate hyperplasia and androgen deficiency.

BACKGROUND: The present clinical trial was conducted to evaluate the efficacy and tolerability of a standardized saw palmetto oil containing 3% ß-sitosterol in the treatment of benign prostate hyperplasia (BPH) and androgen deficiency. METHODS: Subjects aged 40-65 years with symptomatic BPH were randomized to 12-week double-blind treatment with 500 mg doses of ß-sitosterol enriched saw palmetto oil, conventional saw palmetto oil and placebo orally in the form of capsules (n = 33 in each group). BPH severity was determined using the International Prostate Symptom Score (IPSS), uroflowmetry, serum measurement of prostate specific antigen (PSA), testosterone and 5α-reductase. During the trial, the androgen deficiency was evaluated using Aging Male Symptoms (AMS) scale, the Androgen Deficiency in the Aging Male (ADAM) questionnaire, serum levels of free testosterone. RESULTS: Subjects treated with ß-sitosterol enriched saw palmetto oil showed significant decrease in IPSS, AMS and ADAM scores along with reduced postvoiding residual volume (p < 0.001), PSA (p < 0.01) and 5α-reductase from baseline to end of 12-week treatment as compared to placebo. There was also a significant increment in the maximum and average urine flow rate (p < 0.001), and serum free testosterone level of subjects treated with enriched saw palmetto oil as compared to placebo. CONCLUSION: This study demonstrates the efficacy of ß-sitosterol enriched saw palmetto oil superior to conventional oil thus extending the scope of effective BPH and androgen deficiency treatment with improved quality of life through the intake of functional ingredients. TRIAL REGISTRATION: CTRI/2018/12/016724 dated 19/12/2018 prospectively registered. URL: http://ctri.nic.in/Clinicaltrials/advsearch.php.

Curcumagalactomannoside/Glucosamine Combination Improved Joint Health Among Osteoarthritic Subjects as Compared to Chondroitin Sulfate/Glucosamine: Double-Blinded, Randomized Controlled Study.

Objective: A combination of curcumagalactomannosides (CGM) (400 mg) with glucosamine hydrochloride (GLN) (500 mg) was evaluated against a standard dietary supplement combination chondroitin sulfate (CHN) (415 mg)/GLN (500 mg) for their effectiveness in alleviating the pain and symptoms among osteoarthritic subjects. Design: Randomized, double-blinded and active-controlled study. Settings/Location: The study was conducted in a hospital-based research center in Vadodara, Gujarat, India. Subjects: Eighty subjects (38 males and 42 females), with confirmed osteoarthritis (OA) (Class I-III), were randomized into two parallel groups designated as Group I (CGM-GLN) and Group II (CHN-GLN). Interventions: All the study subjects were supplemented with their corresponding intervention capsules (ether CGM along with GLN or CHN along with GLN), as a single oral dose twice a day, once in the morning 10-15 min before breakfast and again in the evening before dinner, for 84 days. Outcome measures: A validated treadmill uphill walking protocol was used for the study, and the efficiency of supplementation was evaluated using visual analogue scale (VAS) score, Karnofsky Performance Scale (KPS) score, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire at the baseline, 28th, and 84th day following the treatment. Mechanism of action of CGM-GLN combination was analyzed by measuring the levels of serum inflammatory markers interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), and soluble vascular cell adhesion molecule-1 (sVCAM) at the baseline and 84th day. Results: CGM-GLN was found to offer significant beneficial effects to pain, stiffness, and physical function of OA subjects compared with CHN-GLN, which was evident from the improvement in walking performance, VAS score, KPS score, and WOMAC score. The efficiency of CGM-GLN was almost double compared with the CHN-GLN by the end of the study (84th day). A significant reduction of inflammatory serum marker levels was observed among CGM-GLN subjects compared with CHN-GLN subjects. Compared with the baseline, CGM-GLN produced 54.52%, 59.08%, and 22.03% reduction in IL-1ß, IL-6, and sVCAM levels, respectively. Whereas CHN-GLN group of subjects expressed only 23.17%, 21.38%, and 6.82% reduction in IL-1ß, IL-6, and sVCAM levels, respectively. Conclusions: In conclusion, the present study demonstrated the potential benefits of CGM-GLN supplements in alleviating the symptoms and function of OA subjects compared with the standard CHN-GLN treatment. The augmented efficacy of CGM-GLN combination could be attributed to the enhanced anti-inflammatory effect of CGM.

A Novel Curcumin-Galactomannoside Complex Delivery System Improves Hepatic Function Markers in Chronic Alcoholics: A Double-Blinded, randomized, Placebo-Controlled Study.

Considering the recent interest in free (unconjugated) curcuminoids delivery, the present study investigated the efficacy of a novel food-grade free-curcuminoids delivery system (curcumin-galactomannoside complex; CGM) in improving the hepatic function markers (inflammation and oxidative stress) in chronic alcoholics. The double-blinded, placebo-controlled study randomized 48 subjects with elevated serum transaminases and gamma-glutamyl transferase (GGT) levels, who were allocated to two groups (n=24) and to receive either placebo or CGM at (250 mg × 2)/day for 8 weeks. While liver function markers (transaminases and GGT) in the placebo group showed an increase (~ 9.5%), CGM group indicated a significant decrease in transaminases (31%) and GGT (29%) from the baseline levels. The beneficial effect of CGM was also clear from the significant increase (p <0.001) in endogenous antioxidants (GSH, SOD, and GPx) and decrease in inflammatory markers (IL-6 and CRP) levels (p <0.001) as compared to both the baseline and placebo group. To summarize, the nutritional intervention of CGM-curcumin was found to offer a significant hepatoprotective effect to attenuate the alcohol induced alterations to hepatic function markers. The Indian Medical Council and Drug Controller General of India approved Clinical Trial Registry No. CTRI/2018/03/012385.