-
1.
Broccoli sprout supplementation in patients with advanced pancreatic cancer is difficult despite positive effects-results from the POUDER pilot study.
Lozanovski, VJ, Polychronidis, G, Gross, W, Gharabaghi, N, Mehrabi, A, Hackert, T, Schemmer, P, Herr, I
Investigational new drugs. 2020;(3):776-784
-
-
Free full text
-
Abstract
Pancreatic ductal adenocarcinoma is a highly aggressive malignancy with short survival and limited therapeutic options. Broccoli sulforaphane is a promising new treatment due to the results of recent epidemiological, experimental and patient studies. Upon approval from the ethics committee and registration at ClinicalTrials.gov, 40 patients with palliative chemotherapy were placed into a placebo and treatment group in an unblinded fashion. Fifteen capsules with pulverized broccoli sprouts containing 90 mg/508 μmol sulforaphane and 180 mg/411 μmol glucoraphanin or methylcellulose were administered daily for up to 1 year. Twenty-nine patients were included in the treatment group and 11 patients were in the placebo group; these patients were followed for up to 1 year. The patient characteristics, overall survival and feasibility were assessed. Compared to those of the placebo group, the mean death rate was lower in the treatment group during the first 6 months after intake (day 30: 0%/18%, day 90: 0%/25%, and day 180: 25%/43%), and Kaplan-Meier analysis revealed a higher survival rate. There was a high drop-out rate (72% in the treatment group and 55% in the placebo group) after 1 year. We concluded from the Karnofsky index that the broccoli sprouts did not impact patient's self-care and overall abilities severely. The intake of 15 capsules daily was difficult for some patients, and the broccoli sprouts sometimes increased digestive problems, nausea and emesis. We did not obtain statistically significant results (p = 0.291 for the endpoint at day 180), but the knowledge about the feasibility is the basis for the development of new sulforaphane drugs.
-
2.
Natural Skin Care Products as Adjunctive to Prescription Therapy in Moderate to Severe Rosacea.
Draelos, ZD, Gunt, H, Levy, SB
Journal of drugs in dermatology : JDD. 2019;(2):141-146
Abstract
Background: Rosacea is characterized by irritation associated with erythema, telangiectasias and papules/pustules. Whole formula nature-based sensitive skin products are formulated to maintain skin barrier and appropriate hydration that can lead to soothing benefits. Objective: To evaluate the efficacy and tolerability of a regimen consisting of a cleanser containing natural oils, beeswax, and witch hazel and day and night creams containing natural oils, glycerin, and botanical anti-inflammatories (NR); and a synthetic dermatologist-recommended regimen of cetyl alcohol, sodium lauryl sulphate-containing cleanser, and glycerin, polyisobutene-containing lotion (CR) in subjects with rosacea. Methods: 80 female subjects with rosacea who received 6 weeks of 0.75% metronidazole gel, were randomized to receive NR or CR, twice daily, for 4 weeks in conjunction with the gel. Blinded investigator global assessment of rosacea, investigator-rated, and subject-rated overall skin appearance was assessed using a 5-point scale (0=none, 4=severe) at baseline, 2 weeks, and 4 weeks. Noninvasive skin assessments for skin hydration and skin barrier function were made by corneometry and TEWL, respectively. Results: NR resulted in improvement in investigator global assessment of rosacea measures at 4 weeks from baseline (erythema, 28%; telangiectasia, 26%; papules/pustules, 34%: P<0.001) and CR resulted in a 8 to 12% improvement. Differences between treatments were statistically significant. Overall skin appearance measured by the investigator was clinically and statistically improved from baseline by 32% and 12% with NR and CR, respectively. Overall skin appearance measured by subjects was improved by both NR and CR from baseline with no differences between treatments. Both regimens improved barrier function from baseline to week 4 (13%, NR; 14%, CR). NR decreased hydration by 21% from baseline at week 4 while CR increased hydration by 14% (P<0.001 from NR). No clinically significant tolerability issues were reported in either regimen at week 4. Conclusion: NR was effective, well tolerated, and superior to CR in the management of rosacea, concomitantly treated with metronidazole. National Clinical Trial Identifier: NCT03392558 J Drugs Dermatol. 2019;18(2):141-146.
-
3.
Population Pharmacokinetic Analysis of Alirocumab in Healthy Volunteers or Hypercholesterolemic Subjects Using a Michaelis-Menten Approximation of a Target-Mediated Drug Disposition Model-Support for a Biologics License Application Submission: Part I.
Martinez, JM, Brunet, A, Hurbin, F, DiCioccio, AT, Rauch, C, Fabre, D
Clinical pharmacokinetics. 2019;(1):101-113
-
-
Free full text
-
Abstract
BACKGROUND Alirocumab, a human monoclonal antibody, inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) to significantly reduce low-density lipoprotein cholesterol levels; pharmacokinetics (PK) are governed by non-linear, target-mediated drug disposition (TMDD). OBJECTIVES We aimed to develop and qualify a population PK (PopPK) model to characterize the PK profile of alirocumab, evaluate the impact of covariates on alirocumab PK and on individual patient exposures, and estimate individual predicted concentrations for a subsequent PK/pharmacodynamic (PD) analysis. METHODS Data from 13 phase I-III trials of 2799 healthy volunteers or patients with hypercholesterolemia treated with intravenous or subcutaneous alirocumab (13,717 alirocumab concentrations) were included; a Michaelis-Menten approximation of the TMDD model was used to estimate PK parameters and exposures. The final model comprised two compartments with first-order absorption. Elimination from the central compartment was described by linear (CLL) and non-linear Michaelis-Menten clearance (Vm and Km). The model was validated using visual predictive check and bootstrap methods. Patient exposures to alirocumab were computed using individual PK parameters. RESULTS The PopPK model was well-qualified, with the majority of observed alirocumab concentrations in the 2.5th-97.5th predicted percentiles. Covariates responsible for interindividual variability were identified. Body weight and concomitant statin administration impacted CLL, whereas time-varying free PCSK9 concentrations and age affected Km and peripheral distribution volume (V3), respectively. No covariates were clinically meaningful, therefore no dose adjustments were needed. CONCLUSIONS The model explained the between-subject variability, quantified the impact of covariates, and, finally, predicted alirocumab concentrations (subsequently used in a PopPK/PD model, see Part II) and individual exposures.
-
4.
A novel, multi-ingredient supplement to manage elevated blood lipids in patients with no evidence of cardiovascular disease: a pilot study.
Hobbs, T, Caso, R, McMahon, D, Nymark, M
Alternative therapies in health and medicine. 2014;(5):18-23
Abstract
CONTEXT Recent changes in usage guidelines have created the potential for millions more Americans to be prescribed statin medications. Caution should be advised because the risk of adverse effects of statins may outweigh their benefits and preclude their preventive use for patients without confirmed cardiovascular disease (CVD) who present with elevated blood lipids. However, statins have shown some benefit in primary CVD prevention. Red yeast rice (RYR) is a dietary supplement that has been demonstrated to reduce low-density lipoprotein (LDL) cholesterol levels in blood and omega-3 polyunsaturated fatty acids have been shown to reduce blood levels of triglycerides (TGs). Although effective, quality control issues aggravate risk of adverse effects for both of these supplements. Furthermore, low dosages per capsule, which require patients to manage and consume many capsules per day, also may reduce patient compliance to supplementation regimens. OBJECTIVES The authors' objective was to determine the effects of a multi-ingredient supplement (MIS) featuring RYR for primary support of cardiovascular (CV) health in patients who present no CVD history or symptoms other than elevated blood lipids. The MIS was formulated intentionally with a lower dosage of RYR than that used in prior studies in order to reduce the occurrence of adverse effects. Secondary to the objective of managing blood lipids, the authors were interested in determining the effects of the MIS in combination with a high-potency omega-3 polyunsaturated fatty acid supplement and its effect on TG levels and observing whether adverse effects would inhibit patient compliance. DESIGN The research team designed an open-label pilot study following a pre-post pragmatic design. Setting • The study took place at 2 primary care settings. PARTICIPANTS Nineteen patients with hypercholesterolemia were participants in the study. All participants were required to confirm that they had not taken any other pharmaceutical or supplement therapy to treat cholesterol for at least 30 d prior to baseline, establishing a washout period. At completion of the intervention, 3 participants were excluded for noncompliance with the protocol, although they had taken the supplements as directed. INTERVENTION(S): The recommended serving of the MIS supplement consisted of 1 softgel that contained 9 ingredients: a proprietary blend of RYR, bioflavonoids, polycosanol, 525 mg omega-3 fatty acids in the natural TG form (294 mg eicosapentaenoic acid [EPA], 147 mg docosahexaenoic acid [DHA]) as well as other supporting ingredients, resveratrol, coenzyme Q10 (CoQ10), folic acid vitamin B3 (niacin), B6, B12, and black pepper. Each serving of the omega-3 supplement contained 834 mg of omega-3 polyunsaturated fatty acids in the natural TG form (484 mg EPA, 234 mg DHA) and 33 IU vitamin E, (D-α-tocopherol). The studys participants were assigned to a group based on their initial TG levels. Participants with TG levels <140 mg/dL took the MIS only, and participants whose initial TG levels exceeded 140 mg/dL were assigned to take both the MIS and the omega-3 supplement, receiving 1384 mg of omega-3 daily (778 mg EPA, 381 mg DHA). All participants confirmed by poststudy survey that they took the recommended serving of 1 softgel/d of the assigned supplement(s) for a minimum of 30 d. OUTCOME MEASURE(S): At baseline and follow-up, standard venous blood labs were drawn and processed at nationally accredited labs. Although not standardized, all reports contained: total cholesterol, high-density lipoprotein (HDL), LDL, and TG levels. The research team acknowledges that this lack of standardization and additional lipid data, such as very low-density lipoprotein, is a limitation of the study. RESULTS Total cholesterol and LDL decreased significantly, by 12.0% (P = .0004) and 17.3% (P = .0001), respectively, for the 16 participants taking the MIS supplement. Participants with an LDL at baseline greater than 145 mg/dL (n = 7) benefited even more, with total cholesterol and LDL decreasing significantly by 17.1% (P = .01) and 24.5% (P = .0014), respectively. Although the results were not significant, adding the omega-3 supplement to the protocol resulted in a decrease in the TGs of the subgroup taking both supplements (n = 8), with that measure decreasing by 13.1% (P = .27) from baseline compared with a decrease of 2% (P = .95) for all participants. The subgroup taking both the MIS and omega-3 supplements experienced similar decreases in total cholesterol and LDL as participants taking only the MIS. No side effects were reported by participants, and all participants completed the assigned protocol. CONCLUSIONS The MIS supplement decreased total cholesterol and LDL significantly and offers a promising therapy for the management of cholesterol that may enable better patient compliance. The addition of an omega-3 supplement also decreased TGs in the subgroup that received both therapies, although this decrease was not significant, potentially because of the underpowered size of the subgroup. The research team plans future studies with more robust lipid testing and larger numbers of participants to support the findings of the current study.
-
5.
Relationship between adiponectin and leptin, and blood lipids in hyperlipidemia patients treated with red yeast rice.
Lee, CY, Jan, MS, Yu, MC, Lin, CC, Wei, JC, Shih, HC
Forschende Komplementarmedizin (2006). 2013;(3):197-203
Abstract
BACKGROUND This study aimed to investigate the possible relationships between adiponectin and leptin, blood lipids such as total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) as well as other clinical biomarkers in hyperlipidemia patients treated with red yeast rice. METHODS 30 patients with primary hyperlipidemia were recruited, treated with red rice yeast capsules 600 mg twice a day for 8 weeks, and followed up for 4 weeks. The primary endpoint was the mean difference in LDL-C from baseline to week 8, while the secondary endpoints were the mean percentage changes from baseline of total cholesterol, TG, HDL-C, adiponectin, and leptin. RESULTS At week 8, the decrease in LDL-C and total cholesterol was -38.11 ± 30.90 mg/dl (p < 0.0001) and -44.54 ± 27.46 mg/dl (p < 0.0001), respectively, and the increase in adiponectin was 35.83 ± 67.85 μg/ml (p = 0.017) as compared to baseline. Adiponectin also correlated positively with HDL-C (r2 = 0.39; p = 0.001). Serum leptin correlated negatively with TG (r2 = 0.19; p = 0.035), and there was a trend of correlation between leptin and HDL-C, but this was not statistically significant (r2 = 0.16; p = 0.052). CONCLUSION Red yeast rice can significantly increase adiponectin and can significantly lower LDL-C and total cholesterol levels. Adiponectin correlates positively with HDL-C while serum leptin correlates negatively with TG. Red yeast rice has a potentially protective effect in obesity-related and cardiovascular diseases.
-
6.
A natural product telomerase activator as part of a health maintenance program.
Harley, CB, Liu, W, Blasco, M, Vera, E, Andrews, WH, Briggs, LA, Raffaele, JM
Rejuvenation research. 2011;(1):45-56
-
-
Free full text
-
Abstract
Most human cells lack sufficient telomerase to maintain telomeres, hence these genetic elements shorten with time and stress, contributing to aging and disease. In January, 2007, a commercial health maintenance program, PattonProtocol-1, was launched that included a natural product-derived telomerase activator (TA-65®, 10-50 mg daily), a comprehensive dietary supplement pack, and physician counseling/laboratory tests at baseline and every 3-6 months thereafter. We report here analysis of the first year of data focusing on the immune system. Low nanomolar levels of TA-65® moderately activated telomerase in human keratinocytes, fibroblasts, and immune cells in culture; similar plasma levels of TA-65® were achieved in pilot human pharmacokinetic studies with single 10- to 50-mg doses. The most striking in vivo effects were declines in the percent senescent cytotoxic (CD8(+)/CD28(-)) T cells (1.5, 4.4, 8.6, and 7.5% at 3, 6, 9, and 12 months, respectively; p = not significant [N.S.], 0.018, 0.0024, 0.0062) and natural killer cells at 6 and 12 months (p = 0.028 and 0.00013, respectively). Most of these decreases were seen in cytomegalovirus (CMV) seropositive subjects. In a subset of subjects, the distribution of telomere lengths in leukocytes at baseline and 12 months was measured. Although mean telomere length did not increase, there was a significant reduction in the percent short (<4 kbp) telomeres (p = 0.037). No adverse events were attributed to PattonProtocol-1. We conclude that the protocol lengthens critically short telomeres and remodels the relative proportions of circulating leukocytes of CMV(+) subjects toward the more "youthful" profile of CMV(-) subjects. Controlled randomized trials are planned to assess TA-65®-specific effects in humans.
-
7.
[Etiology of acute enteric infection in children with arid zone and effect of probiotics].
Utemuradova, GE
Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2009;(3):98-100
Abstract
AIM: To study etiologic structure of acute enteric infections (AEI) with isolation of hemolytic and enteropathogenic Escherichia and to assess the efficacy of probiotic therapy during infections caused by E. coli. MATERIALS AND METHODS Bacteriologic tests were performed in 245 children < 3 years old with acute enteric infection. Influence of Colibacterin and Bifidumbacterin preparations on the dynamics of infectious process was assessed. RESULTS Hemolytic Escherichia, enteropathogenic E. coli, Shigella spp., and Salmonella spp. were isolated in 47.3%, 12.2%, 18.3%, and 1.8% of patients with AEI, respectively. The cause of AEI was identified in 77.1% of cases. Bifidumbacterin had good therapeutic effect on infections caused by pathogenic E. coli including its hemolytic forms. CONCLUSION Treatment with Bifidumbacterin improved state of the patients and resulted in suppression of growth of hemolytic Escherichia in the gut. Colibacterin had a good therapeutic effect in the group of patients with domination of staphylococci, enterococci, Proteus in the gut as well as in patients with isolated Shigella and Salmonella. Colibacterin is contraindicated in cases of colonization of the intestine by hemolytic E. coli.
-
8.
Revisiting the Cancer and Leukemia Group B/Southwest Oncology Group 80405 Trial: a phase III trial of chemotherapy and biologic agents for patients with untreated advanced colorectal adenocarcinoma.
Venook, AP, Blanke, CD, Niedzwiecki, D, Lenz, HJ, Taylor, JR, Hollis, DR, Sutherland, S, Goldberg, RM
Clinical colorectal cancer. 2007;(7):536-8
-
9.
Additional food folate derived exclusively from natural sources improves folate status in young women with the MTHFR 677 CC or TT genotype.
Hung, J, Yang, TL, Urrutia, TF, Li, R, Perry, CA, Hata, H, Cogger, EA, Moriarty, DJ, Caudill, MA
The Journal of nutritional biochemistry. 2006;(11):728-34
Abstract
The effectiveness of additional food folate in improving folate status in humans is uncertain particularly in people with the common genetic variant (677 C-->T) in the methylenetetrahydrofolate reductase (MTHFR) gene. To examine the effect of a doubling of food folate consumption on folate status response variables, women (n=32; 18-46 years) with the MTHFR 677 CC or TT genotype consumed either 400 (n=15; 7 CC and 8 TT) or 800 (n=17; 8 CC and 9 TT) microg/day of dietary folate equivalents (DFE) derived exclusively from naturally occurring food folate for 12 weeks. A repeated measures two-factor ANOVA was used to examine the effect of the dietary treatment, the MTHFR C677T genotype and their interactions on serum folate, RBC folate and plasma total homocysteine (tHcy) during the last 3 weeks of the study. Consumption of 800 microg DFE/day resulted in serum folate concentrations that were 67% (P=.005) higher than consumption of 400 microg DFE/day (18.6+/-2.9 vs. 31.0+/-2.7 nmol/L, respectively) and RBC folate concentrations that were 33% (P=.001) higher (1172+/-75 vs. 1559+/-70 nmol/L, respectively). Serum folate (P=.065) and RBC folate (P=.022) concentrations were lower and plasma tHcy was higher (P=.039) in women with the MTHFR 677 TT genotype relative to the CC genotype. However, no genotype by dietary treatment interaction was detected. These data suggest that a doubling of food folate intake will lead to marked improvements in folate status in women with the MTHFR 677 CC or TT genotype.
-
10.
Cancer and Leukemia Group B/Southwest Oncology Group trial 80405: a phase III trial of chemotherapy and biologics for patients with untreated advanced colorectal adenocarcinoma.
Venook, AP, Blanke, CD, Niedzwiecki, D, Lenz, HJ, Taylor, JR, Hollis, DR, Sutherland, S, Goldberg, RM
Clinical colorectal cancer. 2005;(4):292-4