Bioavailability of calcium in an enriched postbiotic system compared to calcium citrate in healthy postmenopausal females; A randomized, double-blind, comparator-controlled, crossover study.

Introduction: Bioavailability of calcium is an important consideration when designing supplements for achieving adequate calcium intake, mainly in high-risk, and aged populations. Alternative supplementation strategies may be able to circumvent absorption issues commonly seen with calcium supplements. The objective of this study was to assess the bioavailability of a single serving of two calcium formulations vs. comparator product in healthy postmenopausal women. Methods: A total of 24 participants between 45 and 65 years were enrolled in a randomized, double-blind, three-phase, crossover study, with a 7-day washout period between phases. The bioavailability of calcium from calcium-carrying Saccharomyces cerevisiae (Ca-SC) or calcium-carrying Lactobacillus (Ca-LAB) in the form of postbiotic products versus calcium citrate, a conventional salt-based calcium supplement, was determined. Each product provided 630 mg of calcium and 400 IU of vitamin D3. After a 14-h (overnight) fast followed by a single dose of product with a standard low-calcium breakfast, both serum and urine calcium concentrations were assessed for up to 8 and 24 h, respectively. Results: Ca-LAB resulted in greater calcium bioavailability, demonstrated by significantly higher area under the curve and peak concentration both in blood and urine, and total calcium mass excreted in urine. The bioavailability of calcium was similar for Ca-SC and calcium citrate except for the peak concentration value that was significantly higher for calcium citrate. Both Ca-LAB and Ca-SC were well tolerated with no significant difference in adverse events between the products during the study. Discussion: These findings suggest that calcium enriched in a Lactobacillus-based postbiotic system is associated with higher levels of bioavailability as compared to calcium citrate, while a calcium-enriched yeast-based postbiotic does not influence calcium absorption.

A Randomized, Double-Blind, Placebo-Controlled, Parallel Study Investigating the Efficacy of a Whole Coffee Cherry Extract and Phosphatidylserine Formulation on Cognitive Performance of Healthy Adults with Self-Perceived Memory Problems.

INTRODUCTION: Cognition refers to brain functions including memory, learning, and thought processing and is increasingly important to individuals. However, impairment of cognitive function is a concern among North American adults. Therefore, effective and reliable treatments are needed. METHODS: This randomized, double-blind, placebo-controlled study examined the effects of 42 days of Neuriva® supplementation, a whole coffee cherry extract and phosphatidylserine supplement, on memory, accuracy, focus and concentration and learning among 138 healthy adults (40-65 years) with self-reported memory problems. Plasma brain-derived neurotrophic factor (BDNF) levels, Computerized Mental Performance Assessment System (COMPASS) tasks, the Everyday Memory Questionnaire (EMQ), and Go/No-Go tests were assessed at baseline and day 42. RESULTS: As compared to placebo, Neuriva® supplementation elicited greater improvements at day 42 in numeric working memory COMPASS task accuracy outcomes (p ≤ 0.024) which assessed memory, accuracy, and focus and concentration, and reaction time outcomes (p ≤ 0.031) which assessed memory as well as focus and concentration. Neuriva® supplementation improved overall accuracy (p = 0.035) in the picture recognition task that assessed memory, accuracy, and learning compared to placebo. No significant differences between groups were observed for BDNF, the EMQ, or Go/No-Go tests. CONCLUSION: Results suggest 42 days of Neuriva® supplementation was safe, well tolerated, and beneficial in improving memory, accuracy, focus and concentration, and learning in a healthy adult population with self-reported memory problems.

Consuming a Protein and Fiber-Based Supplement Preload Promotes Weight Loss and Alters Metabolic Markers in Overweight Adults in a 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Higher protein and fiber diets promote weight management and metabolic health. OBJECTIVES: This study aimed to determine if greater weight loss and positive changes in metabolic outcomes could be achieved with twice-daily consumption of a high-protein and fiber-based multi-ingredient nutritional shake (HPF) compared with an isocaloric low-protein, lower fiber-based placebo (LPF). METHODS: Study procedures were conducted by an independent research organization under clinicaltrials.gov registration NCT03057873. Healthy overweight and obese adults [n = 206; BMI (kg/m2): 27-35; 70% female] were randomly assigned to HPF or LPF. All participants were prescribed an energy-restricted diet (500 kcal/d less than energy needs) and consumed a HPF (17 g protein, 6 g fiber) or LPF (1 g protein, 3 g fiber) shake 30 min before breakfast and lunch for 12 wk. Primary outcomes included body weight and total body fat percentage. Blood samples were collected at days (D) 0, 28, 56, and 84 for secondary analyses related to metabolic markers of health. RESULTS: Although weight loss occurred in both groups, HPF had greater weight loss at D84 compared with LPF (-3.3 kg vs. -1.8 kg, P < 0.05). Percentage body fat decreased in both groups (HPF: -1.33%, LPF: -1.09%; P < 0.001) with no differences between groups. Serum total cholesterol, LDL cholesterol, and oxidized LDL decreased between -5.1% to -8.3%, whereas adiponectin increased over time in both groups; these changes occurred to a greater extent in HPF compared with LPF (all P < 0.05). CONCLUSIONS: A multi-ingredient HPF nutritional supplement shake consumed as a preload before breakfast and lunch positively influenced weight management and metabolic outcomes in overweight adults compared with an LPF placebo. These findings suggest that specific nutrient factors (i.e., potentially including protein, fiber, and bioactive content) other than calorie reduction alone influence the success of a weight-loss regimen. This trial was registered at www.clinicaltrials.gov as NCT03057873.

A Randomized, Double-blind, Placebo-controlled, Parallel Study Evaluating the Efficacy of Bacillus subtilis MB40 to Reduce Abdominal Discomfort, Gas, and Bloating.

INTRODUCTION: Bloating is a common yet poorly managed complaint among healthy people, with a complex etiology that impacts health and general well-being. The study intended to evaluate the efficacy and safety of supplementation with a probiotic, Bacillus subtilis MB40 (MB40), on bloating, abdominal discomfort, and gas in healthy participants. METHODS: In this multi-center, double-blind, placebo-controlled, parallel trial, 100 participants were randomized to receive either MB40 at 5 × 109 colony forming units (CFU; n = 50) or a placebo (n = 50) once daily for 4-weeks. Participants completed 3 questionnaires daily: a modified Abdominal Discomfort, Gas, and Bloating (mADGB) questionnaire, a modified Gastrointestinal Symptoms Rating Scale (mGSRS), and a Bowel Habits Diary (BHD). Participants' responses to each question were combined into weekly averages. RESULTS: At the end of 4-weeks, there were no significant differences in average weekly change in daily bloating intensity, number of days with and duration of bloating, abdominal discomfort and gas between MB40 and placebo groups. However, the male sub-group on MB40 achieved clinical thresholds with a greater decrease over placebo in the intensity of (1.38) and number of days with (1.32) bloating, the number of days (1.06) and duration (86-minutes) of gas, the number of days with abdominal discomfort (1.32) and diarrhea symptom score (1.02). Role limitation (physical; P = .026), vitality (P = .034) and social functioning (P = .037) were significantly improved from baseline to week 4 in the MB40 group. At 2-weeks, physical functioning (P = .017) significantly improved in the MB40 group versus placebo. CONCLUSIONS: Although MB40 supplementation did not significantly improve bloating across all populations, the male sub-group demonstrated clinically significant reductions in bloating intensity, number of days with abdominal discomfort, gas, bloating, and duration of gas, compared to placebo. Additionally, the male sub-group receiving MB40 had a 10% improvement in general health score. MB40 supplementation at a dose of 5 × 109 CFU daily for 4-weeks was also safe and well-tolerated as all biometric, vital, and hematological measures remained within normal laboratory ranges (Clinical Trials NCT02950012).

Pain Bloc-R Alleviates Unresolved, Non-Pathological Aches and Discomfort in Healthy Adults-A Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

The lack of effective treatment for chronic discomfort without negative side effects highlights the need for alternative treatments. Pain Bloc-R is a natural health product composed of vitamins B6, B12, D, white willow bark extract, Angelica root extract, acetyl L-carnitine HCl, caffeine, L-theanine, Benfotiamine, and L-tetrahydropalmatine. The objective of this study was to compare the effects of Pain Bloc-R, acetaminophen, and placebo on unresolved aches and discomfort as assessed by the brief pain inventory (BPI) and modified Cornell musculoskeletal discomfort questionnaires. This randomized, double-blind, placebo-controlled, crossover study consisted of three 7-day periods with Pain Bloc-R, acetaminophen, or placebo, each separated by a 7-day washout. Twenty-seven healthy adults (ages 22-63 years) were randomized to receive the three interventions in different sequences. The BPI "pain at its worst" scores were significantly lower when participants took Pain Bloc-R than when they took acetaminophen (21.8% vs. 9.8% decrease, p = 0.026) after seven days of supplementation. Pain Bloc-R achieved a significant improvement in the "pain at its least" score, significantly decreased the interference of discomfort in walking, and significantly decreased musculoskeletal discomfort total scores (34%, p = 0.040) after seven days. In a post hoc subgroup analysis based on age and gender, male participants ≤45 years taking Pain Bloc-R reported significant reductions in pain severity and pain interference vs. acetaminophen. Pain Bloc-R performed as well as acetaminophen in managing unresolved non-pathological pain in otherwise healthy individuals.

Efficacy of Lactobacillus paracasei HA-196 and Bifidobacterium longum R0175 in Alleviating Symptoms of Irritable Bowel Syndrome (IBS): A Randomized, Placebo-Controlled Study.

Specific probiotic strains can alleviate the gastrointestinal (GI) symptoms and psychiatric comorbidities of irritable bowel syndrome (IBS). In this randomized, double-blind, placebo-controlled study, the efficacy of Lactobacillus paracasei HA-196 (L. paracasei) and Bifidobacterium longum R0175 (B. longum) in reducing the GI and psychological symptoms of IBS was evaluated in 251 adults with either constipation (IBS-C), diarrhea (IBS-D), or mixed-pattern (IBS-M). Following a 2-week run-in period, participants were randomized to one of three interventions: L. paracasei (n = 84), B. longum (n = 83) or placebo (n = 81). IBS symptoms, stool frequency and consistency and quality of life were assessed by questionnaires. The differences from baseline in the severity of IBS symptoms at 4 and 8 weeks were similar between groups. Participants in this study were classified, after randomization, into subtypes according to Rome III. Within the L. paracasei group, complete spontaneous and spontaneous bowel movement frequency increased in participants with IBS-C (n = 10) after 8 weeks of supplementation (both p < 0.05) and decreased in participants with IBS-D (n = 10, p = 0.013). Both L. paracasei and B. longum supplementation improved the quality of life in emotional well-being and social functioning compared with baseline (all p < 0.05). In conclusion, L. paracasei and B. longum may reduce GI symptom severity and improve the psychological well-being of individuals with certain IBS subtypes.

A Whole-Food-Based Health Product (A-F Betafood®) Improves Gallbladder Function in Humans at Risk of Gallbladder Insufficiency: A Randomized, Placebo-Controlled Clinical Trial.

A-F Betafood® is a whole food-based health product. The product contains phytonutrients and bioactives with antioxidant properties that may support gallbladder and liver function. Herein, we investigated the efficacy of A-F Betafood® on gallbladder and liver function. In this randomized, placebo-controlled, parallel study fifty overweight but otherwise healthy adults received A-F Betafood® or placebo for 12 weeks. Gallbladder function as assessed by gallbladder volume, ejection fraction (GBEF), ejection rate, wall thickness and liver function determined via aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase, and high-sensitivity c-reactive protein analysis at baseline and week 12 were the primary outcomes. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides, and oxidative stress markers including oxidized low-density lipoprotein, tumor necrosis factor-α, adiponectin and malonyldialdehyde (MDA) were assessed as secondary outcomes. A-F Betafood®-supplementation significantly reduced gallbladder wall thickness (p = 0.049) by 9% compared to placebo from baseline to week 12. The A-F Betafood® group alone had significant improvements in gallbladder volume (32%; p = 0.044) and GBEF (19%; p = 0.047) at week 12. There were no changes in liver function, oxidative stress markers or blood lipid concentrations, though MDA concentrations decreased in both groups. Our findings demonstrate A-F Betafood®-supplementation significantly improves measures of gallbladder function and support healthy gallbladder function in the individuals with gall bladder condition.

Vitamin C Bioequivalence from Gummy and Caplet Sources in Healthy Adults: A Randomized-Controlled Trial.

Background: The efficacy of Vitamin C (L-ascorbic acid) supplementation can be assessed by uptake into the blood and retention in leukocytes. Vitafusion® Power C gummy is an alternative vitamin C source which may exhibit similar bioavailability to comparator caplets.Objective: The objective of this study was to evaluate the bioequivalence of vitamin C from a vitafusion® Power C gummy formulation and a comparator caplet in healthy adults.Methods: Thirty healthy men and women, 34.0 ± 11.4 years of age and Body Mass Index (BMI) 24.5 ± 3.6 kg/m2 completed the randomized examiner-blind, comparator controlled, cross-over trial with two sequences: gummy (1000 mg) to caplet (1000 mg) or caplet to gummy. Intake of foods fortified with Vitamin C was restricted 7 days prior to each dosing. Blood samples were collected pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 24 h post-dose for plasma and leukocytes; and urine was collected pre-dose and between 0-2, 2-4, 4-8, 8-12 and 12-24 h post-dose for L-ascorbic acid analysis.Results: Vitafusion® Power C gummy and comparator caplet demonstrated similar plasma absorption profiles as there were no significant differences in plasma L-ascorbic acid total Area Under the Curve (AUC)0-24h, and Tmax between gummy and caplet. The caplet did elicit a significantly higher Cmax than the gummy (p < 0.05), however, the difference was numerically small. Leukocyte L-ascorbic acid total AUC0-24h and Cmax were not significantly different between gummy and caplet, however Tmax of the gummy group was significantly longer (p = 0.012). Urinary L-ascorbic acid levels were also not significantly different between gummy and caplet. There were no serious adverse events and safety parameters remained within normal clinical range for both products.Conclusion: Vitafusion® Power C gummy exhibited similar Vitamin C absorption and bioavailability to a comparator caplet in healthy adults and were considered bioequivalent.

Effect of a Euglena gracilis Fermentate on Immune Function in Healthy, Active Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.

Euglena gracilis produce high amounts of algal ß-1,3-glucan, which evoke an immune response when consumed. This study investigated the effect of supplementation with a proprietary Euglena gracilis fermentate (BG), containing greater than 50% ß-1,3-glucan, on immune function as measured by self-reported changes in upper respiratory tract infection (URTI) symptoms. Thirty-four healthy, endurance-trained participants were randomized and received either 367 mg of BG or placebo (PLA) for 90 days. Symptoms were assessed by the 24-item Wisconsin Upper Respiratory Symptom Survey and safety via clinical chemistry, hematology, vitals, and adverse event reporting. Participants supplemented with BG over 90 days reported fewer sick days (BG: 1.46 ± 1.01; PLA: 4.79 ± 1.47 days; p = 0.041), fewer URTI symptoms (BG: 12.62 ± 5.92; PLA: 42.29 ± 13.17; p = 0.029), fewer symptom days (BG: 5.46 ± 1.89; PLA: 15.43 ± 4.59 days; p = 0.019), fewer episodes (BG: 2.62 ± 0.67; PLA: 4.79 ± 0.67; p = 0.032), and lower global severity measured as area under curve for URTI symptoms (BG: 17.50 ± 8.41; PLA: 89.79 ± 38.92; p = 0.0499) per person compared to placebo. Sick days, symptoms, and global severity were significantly (p < 0.05) fewer over 30 days in the BG group compared to PLA. All safety outcomes were within clinically normal ranges. The study provides evidence that supplementation with a proprietary Euglena gracilis fermentate containing greater than 50% ß-1,3-glucan may reduce and prevent URTI symptoms, providing immune support and protecting overall health.

Efficacy of Polydextrose Supplementation on Colonic Transit Time, Bowel Movements, and Gastrointestinal Symptoms in Adults: A Double-Blind, Randomized, Placebo-Controlled Trial.

The addition of fiber is one of the most important dietary means to relieve constipation through lifestyle modification. Polydextrose (PDX) has been reported in several studies to increase fecal bulk, soften stools, and increase the number of defecations. However, there are few studies on the effect of PDX on colonic transit time (CTT). Therefore, the aim of this study was to demonstrate the effect of PDX on CTT and other aspects of gastrointestinal function during two weeks (Day 1 to Day 14), preceded by a 2-week run-in period (Day -14 to Day -1). A total of 192 adults who were diagnosed with functional constipation per Rome III criteria were recruited for the study. Participants were randomized equally into 4 groups (12 g, 8 g, or 4 g of PDX or placebo per day). The primary endpoint was CTT, assessed using radio-opaque markers and abdominal X-rays on Day 0, the baseline; and Day 15, the end of the intervention. Secondary outcomes that were measured using inventories were the patient assessment of constipation symptoms and quality of life, bowel function index, relief of constipation, bowel movement frequency (BMF), stool consistency, degree of straining, and proportion of bowel movements. Ancillary parameters and harms were also evaluated. The recruited population was not sufficiently constipated (e.g., baseline values for CTT and BMF of 42 h and 8.7 BMF/week, respectively). Despite this limitation, our results demonstrated an increased number of bowel movements when supplemented with PDX at a dosage of 12 g per day for 2 weeks. This dosage also consistently improved the secondary outcomes that were measured using inventories at Day 15, compared with the baseline. No serious or significant adverse events were reported during the study.

A Randomized Double-Blind, Placebo Controlled, Four-Arm Parallel Study Investigating the Effect of a Broad-Spectrum Wellness Beverage on Mood State in Healthy, Moderately Stressed Adults.

OBJECTIVE: The objective of this study was to investigate the effect of a broad-spectrum wellness beverage (Zeal Wellness [ZW]) on standardized measures of mood states, including overall feelings of vitality, in healthy, moderately stressed adults. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted among 99 eligible participants prescreened for moderate stress. Participants were randomized to one of four groups and received ZW once daily (1-dose-ZW; 14 g), ZW twice daily (2-dose-ZW; 28 g), placebo once daily (1-dose-placebo), or placebo twice daily (2-dose-placebo) for 4 weeks. A stress/vitality questionnaire assessed stress and the Profile of Moods (POMS) Questionnaire assessed vigor via mental/physical energy and global mood state. Safety was assessed by clinical chemistry, liver, kidney function, and anthropometric measures and adverse event reporting. RESULTS: Participants receiving 2-dose-ZW reported a 6.6% decrease in scores on POMS-Total Mood Disturbance (TMD; p < 0.05) and a 6.8% decrease in the anger-hostility mood state (p < 0.022) compared to the combined placebo group at day 29. The 2-dose-ZW provided a 12.8% greater improvement in POMS-TMD scores when compared to participants receiving 1-dose-ZW after 28 days of supplementation (p = 0.014). Within groups, there was a 22.4% and a 9.6% decrease in POMS-TMD scores in participants with 2-dose-ZW and 1-dose-ZW, respectively. In addition, participants receiving 2-dose-ZW showed significant improvements (p = 0.001) in the POMS t-score iceberg profile, which represented a shift to a more healthy profile. CONCLUSION: These data show that daily supplementation with 2-dose-ZW significantly decreased POMS-TMD scores and anger-hostility mood state and shifted the POMS iceberg profile to a healthy profile compared to the combined placebo, reflecting the functional benefit of rice-bran-fruit-vegetable extracts based beverage on health.

Efficacy of a novel formulation of L-Carnitine, creatine, and leucine on lean body mass and functional muscle strength in healthy older adults: a randomized, double-blind placebo-controlled study.

BACKGROUND: Progressive decline in skeletal muscle mass and function are growing concerns in an aging population. Diet and physical activity are important for muscle maintenance but these requirements are not always met. This highlights the potential for nutritional supplementation. As a primary objective, we sought to assess the effect of a novel combination of L-Carnitine, creatine and leucine on muscle mass and performance in older subjects. METHOD: Forty-two healthy older adults aged 55-70 years were randomized to receive either a novel L-Carnitine (1500 mg), L-leucine (2000 mg), creatine (3000 mg), Vitamin D3 (10 µg) (L-Carnitine-combination) product (n = 14), L-Carnitine (1500 mg) (n = 14), or a placebo (n = 14) for eight weeks. We evaluated body mass by DXA, upper and lower strength by dynamometry, and walking distance by a 6-min walk test at baseline and after eight weeks of intervention. These measures, reflecting muscle mass, functional strength and mobility have been combined to generate a primary composite score. Quality of life, blood safety markers, and muscle biopsies for protein biomarker analysis were also conducted at baseline and the end of the study. RESULTS: The primary composite outcome improved by 63.5 percentage points in the L-Carnitine-combination group vs. placebo (P = 0.013). However, this composite score did not change significantly in the L-Carnitine group (P = 0.232), and decreased slightly in the placebo group (P = 0.534). Participants supplemented with the L-Carnitine-combination showed a 1.0 kg increase in total lean muscle mass (P = 0.013), leg lean muscle mass (0.35 kg, P = 0.005), and a 1.0 kg increase in lower leg strength (P = 0.029) at week 8. In addition, these increases were significant when compared to the placebo group (P = 0.034, P = 0.026, and P = 0.002, respectively). Total mTOR protein expression was increased in participants in the L-Carnitine-combination group at the end of the study compared to the baseline (P = 0.017). This increase was also significant when compared to the placebo (P = 0.039), suggesting that the increase in muscle mass and strength was due to new protein synthesis and mTOR pathway activation. CONCLUSIONS: The trial did reach its primary objective. L-Carnitine combined with creatine and L-leucine significantly improved the composite score which reflects muscle mass and strength, at the end of the study compared to placebo. The combination showed an increase in mTOR protein level, a driver for increased muscle mass which translated to an improvement in muscle strength. This new combination may provide a potential nutritional intervention to promote muscle growth and improved physical functioning in older adults.

Effectiveness of Lactobacillus helveticus and Lactobacillus rhamnosus for the management of antibiotic-associated diarrhoea in healthy adults: a randomised, double-blind, placebo-controlled trial.

Broad-spectrum antibiotic use can disrupt the gastrointestinal microbiota resulting in diarrhoea. Probiotics may be beneficial in managing this type of diarrhoea. The aim of this 10-week randomised, double-blind, placebo-controlled, parallel study was to investigate the effect of Lactobacillus helveticus R0052 and Lactobacillus rhamnosus R0011 supplementation on antibiotic-associated diarrhoea in healthy adults. Subjects were randomised to receive 1 week of amoxicillin-clavulanic acid (875 mg/125 mg) once per day, plus a daily dose of 8×109 colony-forming units of a multi-strain probiotic (n 80) or placebo (n 80). The probiotic or placebo intervention was maintained for 1 week after completion of the antibiotic. Primary study outcomes of consistency and frequency of bowel movements were not significantly different between the probiotic and placebo groups. The secondary outcomes of diarrhoea-like defecations, Gastrointestinal Symptoms Rating Scale scores, safety parameters and adverse events were not significantly different between the probiotic intervention and the placebo. A post hoc analysis on the duration of diarrhoea-like defecations showed that probiotic intervention reduced the length of these events by 1 full day (probiotic, 2·70 (sem 0·36) d; placebo, 3·71 (sem 0·36) d; P=0·037; effect size=0·52). In conclusion, this study provides novel evidence that L. helveticus R0052 and L. rhamnosus R0011 supplementation significantly reduced the duration of diarrhoea-like defecations in healthy adults receiving antibiotics.

An open label pilot study to evaluate the efficacy of Spanish black radish on the induction of phase I and phase II enzymes in healthy male subjects.

BACKGROUND: Humans are exposed to toxins which accumulate in the body, and are detoxified primarily in the liver. Studies have shown that cruciferous vegetables (such as radishes) may be beneficial to health by aiding detoxification of toxins in the liver. METHODS: This single-centre, open-label, pilot study investigated the effect of a dietary supplement containing Spanish Black Radish on hepatic function in healthy males by monitoring the profiles of plasma and urine acetaminophen metabolites and serum hormone concentrations at baseline and after 4 weeks of supplementation. A paired t-test was used to compare pre- and post-treatment of plasma and urine acetaminophen metabolite profiles, serum hormone concentrations and safety end points. RESULTS: Area under the curve (AUC) from 0 to 8 hours for the acetaminophen glucuronide metabolite and unchanged acetaminophen in plasma decreased from baseline to week 4 by 9% (P = 0.004) and 40% (P = 0.010), respectively. The AUC from 0 to 8 hours for acetaminophen sulfate and mercapturate metabolites in the urine increased by 11% (P = 0.010) and 37% (P = 0.024), respectively, from baseline to week 4. The AUC from 0 to 8 hours of serum estradiol-17ß decreased by 10% from baseline to week 4 (P = 0.005). All measures of clinical safety remained within acceptable laboratory ranges, however a significant reduction in plasma γ-glutamyl transferase levels was noted after 4 weeks of Spanish Black Radish treatment (P = 0.002). CONCLUSIONS: These changes in metabolite and hormone levels indicate that Spanish Black Radish supplements have a positive influence on the detoxification of acetaminophen suggesting up-regulation of phase I and phase II liver enzymes. This study was sponsored by Standard Process Inc. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT02137590 (Date of registration: May 12, 2014).

Efficacy of a natural mineral complex in North American adults with osteoarthritis of the knee: a randomized double-blind placebo-controlled study.

PURPOSE: This study evaluated the efficacy of a hydrothermal mineral complex (HMC) supplement in participants with knee osteoarthritis. PATIENTS AND METHODS: This was a double-blind, placebo-controlled, 12-week crossover study with 150 participants receiving either placebo or HMC for 4 weeks, with a 4-week washout period. The primary endpoint was WOMAC™ pain, and secondary endpoints were WOMAC™ physical function and stiffness, the 36-Item Short Form Health Survey (SF-36), high-sensitivity C-reactive protein, tumor necrosis factor α, interleukin 6, and safety. RESULTS: There were no significant differences in WOMAC™ pain, stiffness, or physical function scores between groups. Within groups, subjects on both HMC and placebo reported improvements (P<0.001) in all WOMAC™ domains. HMC performed significantly better in total SF-36 scores (P=0.05) and physical function (P=0.02), and had improved total physical activity (P=0.06) and social functioning (P=0.09) scores compared with placebo. Within groups, physical function (P=0.01), limitations due to mental health/emotional well-being (P=0.02), bodily pain (P=0.001), and total physical (P=0.003) and mental health scores (P=0.02) improved in participants on HMC, whereas improvements in bodily pain (P=0.001), general health (P=0.01), and total physical activity (P=0.04) were reported in placebo. Subjects on HMC with body mass index (BMI) <25 kg/m2 showed a trend toward decreased pain scores (P=0.10), while pain increased in those administered placebo. Minimal clinically important improvement (MCII) in WOMAC™ pain scores increased from 28% of HMC-administered participants at week 2 to 41% at week 4, and decreased to 37% after 2 weeks of washout. In comparison, 41% of placebo-administered subjects achieved MCII by week 2 and week 4. A 10.4% greater increase in tumor necrosis factor α levels was seen in participants receiving placebo than those receiving HMC (P=0.07). There were no differences between groups in adverse events. CONCLUSION: HMC significantly improved physical function and total physical activity, improving the quality of life of participants. HMC was most effective in normal-weight subjects. Increased dosage may be required for North American subjects with BMI >25 kg/m2.

Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation.

High serum concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease. The efficacy of pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD) risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP) guidelines. A total of 32 subjects were randomized to pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to 16) or placebo. Compared with placebo, the participants on pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040) and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively), and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively) that reached significance by week 16 (P=0.042). An 11% decrease in LDL-C from baseline was seen in participants on pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027) and 16 (P=0.010). The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants eligible for statins according to NCEP guidelines.

A randomized, double-blind clinical study on the safety and tolerability of an iron multi-amino acid chelate preparation in premenopausal women.

ABSTRACT Considerable risk of iron deficiency has been identified in premenopausal women because of the adverse effects associated with commercial iron preparations. This study examined the safety and tolerability of a novel iron multi-amino acid chelate (IMAAC) preparation in premenopausal women. A single-centre, randomized, double-blind, three-arm placebo-controlled (n = 60) study was conducted where subjects received one of three test materials: IMAAC (600 mg) or ferrous sulfate (600 mg) each containing 25 mg of elemental iron, or placebo as a single daily dose for 7 days. After testing, there were no significant differences found in any of the hematological outcomes between the different test groups. The safety analyses showed that a significantly (p = .044) higher number of patients reported adverse events when taking the ferrous sulfate supplement compared to IMAAC. A significantly lower number of adverse effects (p = .008) were reported by subjects on IMAAC. The current study demonstrated the superiority of the IMAAC preparation over ferrous sulfate with regards to tolerability and adverse effects.

Effects of formulation on the bioavailability of lutein and zeaxanthin: a randomized, double-blind, cross-over, comparative, single-dose study in healthy subjects.

PURPOSE: Lutein and zeaxanthin are macular pigments with a protective function in the retina. These xanthophylls must be obtained from the diet or added to foods or supplements via easy-to-use, stable formulations. The technique employed to produce these formulations may affect the bioavailability of the xanthophylls. METHODS: Forty-eight healthy volunteers were randomized into this double-blind, cross-over study investigating the plasma kinetics of lutein provided as two different beadlet formulations. Subjects (n = 48) received a single dose of 20 mg of lutein as either a starch-matrix ("SMB", FloraGLO® Lutein 5 %) or as a cross-linked alginate-matrix beadlet ("AMB", Lyc-O-Lutein 20 %) formulation. Plasma concentrations of lutein and zeaxanthin were measured at 0, 1, 3, 6, 9, 12, 14, 24, 26, 28, 32, 36, 48, 72, 168, and 672 h. RESULTS: The mean plasma AUC(0-72h), AUC(0-672h), and C(max) for total lutein and zeaxanthin and their all-E-isomers were significantly increased (p < 0.001) from pre-dose concentrations in response to SMB and AMB. There was no difference in lutein T max between the two test articles. However, by 14 h post-dose, total plasma lutein increased by 7 % with AMB and by 126 % with SMB. Total lutein AUC(0-72h) and AUC(0-672h) were 1.8-fold and 1.3-fold higher, respectively, for SMB compared to AMB. Both formulations were well tolerated by subjects in this study. CONCLUSION: These findings confirm that the bioavailability of lutein and zeaxanthin critically depends on the formulation used and document a superiority of the starch-based over the alginate-based product in this study.

A dried yeast fermentate prevents and reduces inflammation in two separate experimental immune models.

Diverse and significant benefits against cold/flu symptoms and seasonal allergies have been observed with a dried fermentate (DF) derived from Saccharomyces cerevisiae (EpiCor) in multiple published randomized trials. To determine if DF may influence other immune conditions, two separate animal studies were conducted. Study 1 examined the ability of DF to prevent or reduce inflammation when given orally for 14 days to rats prior to receiving 1% carrageenan (localized inflammation model). DF significantly (P < 0.05) reduced swelling at all time points (1, 2, 3, 6, 12, and 24 hours) versus the control. Edema severity and PGE2 levels were reduced by approximately 50% and 25% (P < 0.05), respectively. Study 2 examined the ability of DF to treat established inflammation induced by type-2 collagen in mice over 4 weeks (autoimmune arthritis model). Significantly reduced arthritis scores, antibody response to type-2 collagen, and interferon-gamma levels were observed compared to controls (all parameters P < 0.05). DF favorably impacts multiple acute and potentially chronic immunologic inflammatory control mechanisms and should be further tested in clinical trials.

Pantethine, a derivative of vitamin B(5) used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low- to moderate-cardiovascular risk North American subjects: a triple-blinded placebo and diet-controlled investigation.

Safety and efficacy of a biologically active derivative of vitamin B(5) (pantethine) on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) metabolism was studied in North American subjects at conventional low to moderate cardiovascular disease (CVD) risk. A total of 120 subjects initiated a therapeutic lifestyle change (TLC) diet 4 weeks before randomization (baseline) and maintained the diet throughout a 16-week study period; at baseline, subjects were randomized in a triple-blinded manner to either pantethine (600 mg/d, baseline to week 8, and 900 mg/d, weeks 9-16) or identically labeled, nonbiologically active placebo (n = 60 per group). We hypothesized that pantethine would lower TC and low-density lipoprotein in low-CVD-risk North American subjects in a similar manner as reported in high-CVD-risk subjects studied mainly in Italy and Japan. While sustaining a TLC diet and in comparison with placebo, pantethine demonstrated significant (P < .005) and sustained reductions (from baseline to week 16) in TC (6 mg/dL, 0.16 mmol/L, 3%), LDL-C (4 mg/dL, 0.10 mmol/L, 4%), and apolipoprotein B (4 mg/dL, 0.04 g/L, 5%). Our data suggest that pantethine supplementation for 16 weeks (600 mg/d for weeks 1-8 then 900 mg/d for weeks 9-16) is safe and significantly lowers TC and LDL-C over and above the effect of TLC diet alone. Although the absolute magnitude of these effects was small in these low- to moderate-risk North Americans (4-6 mg/dL), the results are noteworthy as prior studies have shown that, for each 1 mg/dL (0.026 mmol/L) reduction in LDL-C, there is a concomitant 1% reduction in overall future CVD risk.