Enzymatically hydrolyzed lactotripeptides do not lower blood pressure in mildly hypertensive subjects 1 3
|
|
- Cora Rice
- 5 years ago
- Views:
Transcription
1 Enzymatically hydrolyzed lactotripeptides do not lower blood pressure in mildly hypertensive subjects 1 3 Kim van der Zander, Michiel L Bots, Annette AA Bak, Mettina MG Koning, and Peter W de Leeuw ABSTRACT Background: Several placebo-controlled clinical studies suggest that products containing isoleucyl-prolyl-proline and valyl-prolylproline are able to lower blood pressure without adverse effects. The most efficient way of producing high concentrations of these lactotripeptides (LTPs) is enzymatic hydrolysis of dairy protein (casein) with the use of a mixture of several enzymes derived from the nongenetically modified organism Aspergillus oryzae, including proteases and peptidases. To date, no large studies of the blood pressure lowering properties of enzymatically produced LTP () powder in European populations have been published. Objective: This study was performed to evaluate the hypothesis that consumption of in a yogurt beverage for 8 wk significantly lowers blood pressure. Design: In this multicenter, double-blind, parallel, placebocontrolled trial, office blood pressure was evaluated in 275 Dutch hypertensive subjects. Blood pressures and body weight were measured on several days at baseline and at weeks 4 and 8 of the intervention between 2.5 and 3 h after intake of the test product. Twentyfour h urine samples were collected at baseline and at the end of the intervention for urinalysis of sodium, potassium, creatinine, and microalbumin excretion. Results: The results showed that 10.2 mg /d does not lead to a reduction in systolic blood pressure (P 0.66) or diastolic blood pressure (P 0.72) compared with placebo. Conclusion: This study showed no effect of an -enriched yogurt beverage on blood pressure in hypertensive subjects in a fairly large study. Am J Clin Nutr 2008;88: INTRODUCTION Several placebo-controlled clinical studies suggest that products containing isoleucyl-prolyl-proline (IPP) and valyl-prolylproline (VPP) are able to lower blood pressure without adverse effects (1 15). Although most of these studies have reported a statistically significant decrease in blood pressure in hypertensive subjects by these lactotripeptides (LTPs), the magnitude of this effect varies considerably. For instance, in Japanese studies, systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased over the 8-wk intervention by 10 and 4 mm Hg, respectively, at a dose between 2 and 4 mg LTP/d (1 10). On the other hand, in Finnish studies, a mean decrease in SBP and DBP of 4 and 2 mm Hg, respectively, was observed at higher doses of 5 6 mg LTP/d (13, 14). Furthermore, an even higher dose of 52.5 mg LTP had only modest effects on 24-h ambulatory SBP and DBP ( 4 and 2 mm Hg, respectively; P and P 0.048, respectively) and did not lower office blood pressure (OBP) at all (15). Because LTP reduced SBP in the European studies to a lesser degree than the anticipated 4 5 mm Hg based on Asian studies, these studies may have been underpowered to show an effect of LTP over and above that of placebo. For clinical studies, 3 different test products containing IPP and VPP are available: directly fermented milk (1 4, 6, 8, 9, 12 15), powdered fermented milk (FLTP powder) (5, 11), and powdered enzymatically hydrolyzed LTP () (7, 10). The most efficient way of producing high concentrations of LTP is the enzymatic hydrolysis of dairy protein (casein) with a mixture of several enzymes derived from the nongenetically modified organism Aspergillus oryzae, including proteases and peptidases (16, 17). After denaturization of the enzymes by sterilization, the resulting dried casein hydrolysate powder ( powder) contains 0.7% LTPs. Japanese researchers have confirmed the blood pressure lowering potential of in animal and human studies (7, 10, 17). We observed a dose-dependent blood pressure lowering effect of on office DBP (P 0.030) but not on SBP (PW de Leeuw, K van der Zander, AA Kroon, RJMW Rennenberg, and MMG Koning, unpublished observations, 2008) in a study of subjects per treatment group. Furthermore, in a recent study, Engberink et al (18) could not support a blood pressure lowering effect of (containing 10.4 mg LTP) compared with placebo in a study of 32 subjects per treatment group. It may be that these studies, which are summarized in Table 1, did not have enough power to show a small but significant effect of any dose of these peptides compared with placebo. To date, no other large studies of the blood pressure lowering properties of in European populations have been published. Therefore, the present study was performed to evaluate the hypothesis that consumption of in a yogurt beverage for 8 wk significantly lowers blood pressure in European hypertensive subjects. 1 From Unilever Food & Health Research Institute, Vlaardingen, Netherlands (KvdZ and MMGK); the Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Netherlands (MLB and AAAB); and the Cardiovascular Research Institute Maastricht and Academic Hospital Maastricht, Maastricht, Netherlands (PWdL). 2 Supported by Unilever Food & Health Research Institute, Vlaardingen, Netherlands. The test products were provided by the Unilever Food & Health Research Institute. 3 Reprints not available. Address correspondence to PW de Leeuw, Department of Medicine, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, Netherlands. p.deleeuw@intmed.unimaas.nl. Received February 14, Accepted for publication August 31, doi: /ajcn Am J Clin Nutr 2008;88: Printed in USA American Society for Nutrition 1697
2 1698 VAN DER ZANDER ET AL TABLE 1 Previous intervention studies on the effects of lactotripeptides (LTPs) on blood pressure 1 Reference Subjects Duration Results Fermented milk Hata et al 1996 (1) 36 grade 1 hypertensive 8 wk Significantly lower SBP (P 0.01) and DBP (P 0.05) compared with baseline Itakura et al 2001 (3) 18 grade 1 hypertensive 8 wk Lower SBP in hypertensive subjects compared with baseline 26 normotensive Kajimoto et al 2001 (4) 36 grade 1 hypertensive 8 wk Significantly lower SBP (P 0.05) and DBP (P 0.05) compared with baseline Hirata et al 2002 (2) 32 grade 1 hypertensive 8 wk Significantly lower SBP (P 0.05) and DBP (P 0.05) compared with baseline Kajimoto et al 2002 (6) 64 grade 1 hypertensive 8 wk Significantly lower SBP (P 0.01) and DBP (P 0.01) compared with baseline Mizushima et al 2004 (8) 46 grade 1 hypertensive 4 wk Lower SBP and DBP compared with baseline Nakamura et al 2004 (9) 106 high normotensive 12 wk Significantly lower SBP (P 0.01) and DBP (P 0.01) compared with baseline Seppo et al 2002 (12) 17 grade 1 hypertensive 8 wk Significantly lower SBP (P 0.05) and DBP (P 0.05) compared with placebo Seppo et al 2003 (13) 39 grade 1 hypertensive 21 wk Significantly lower SBP (P 0.05) compared with placebo Tuomilehto et al 2004 (14) 60/39 grade 1 hypertensive 10/5 wk Lower SBP and DBP compared with baseline/placebo Jauhiainen et al 2005 (15) 94 high normotensive 10 wk Significantly lower SBP (P 0.001) and DBP (P 0.05) compared with placebo FLTP Kajimoto et al 2001 (5) 81 grade 1 hypertensive 8 wk Significantly lower SBP (P 0.001) and DBP (P 0.001) compared with placebo Aihara et al 2005 (11) 40 high normotensive 4 wk Significantly lower DBP (P 0.05) in high-normotensive subjects and 40 grade 1 hypertensive SBP (P 0.01) in hypertensive subjects Engberink et al 2008 (18) 135 grade 1 hypertensive 8 wk No blood pressure lowering effect observed Mizuno et al 2005 (7) 48 high normotensive 6 wk Dose-dependent lower blood pressure 83 grade 1 hypertensive Effect on SBP was significant in hypertensive subjects compared with placebo (P 0.05 for low and middle dose; P 0.01 for high dose) Sano et al 2005 (10) 104 high normotensive 12 wk Significantly lower SBP (P 0.05) in high-normotensive and hypertensive 40 grade 1 hypertensive subjects compared with placebo and DBP (P 0.05) in hypertensive subjects compared with placebo Engberink et al 2008 (18) 135 grade 1 hypertensive 8 wk No blood pressure lowering effect observed 1 SBP, systolic blood pressure; DBP, diastolic blood pressure; FLTP, fermented powdered milk;, enzymatically hydrolyzed LTPs. SUBJECTS AND METHODS Subjects The study was performed at 3 sites located in the Netherlands from September 2005 until March Participants were recruited from Maastricht, Utrecht, and Amersfoort and their surroundings by preselection from databases, through advertisements in newspapers, and by door-to-door flyers. Subjects who expressed their interest in the study completed a telephone screening. Of these subjects, apparently eligible candidates received the information brochure and answered the personal and selection questionnaire. Finally, suitable subjects visited the research centers for screening. Subjects qualified for the study when they were between 35 and 70 y of age, were able to stop antihypertensive medication use 3 wk before screening, and fulfilled the blood pressure criteria. To minimize the risk of misclassification of a person s blood pressure, blood pressure was measured in duplicate on 2 separate screening visits(the second after an overnight fast). Inclusion criteria were an average (based on the 2 visits) systolic blood pressure between 140 and 179 mm Hg and an average diastolic blood pressure 100 mm Hg. Exclusion criteria were the use of blood pressure lowering medication or nonsteroidal anti-inflammatory drug use, abnormal results of biochemical analyses of blood and urine, smoking, unstable weight, alcohol abuse, milk allergy, and pregnancy. The Medical Ethics Committee of the Maastricht University and Academic Hospital approved the study protocol. The Medical Ethics Committee of University Medical Center Utrecht gave local approval (Utrecht and Amersfoort). All participants received both written and oral information and gave their written consent. The study was performed according to the International Conference on Harmonisation Good Clinical Practice guidelines. Study design This study was designed as a multicenter, randomized, doubleblind, parallel, placebo-controlled trial. When subjects qualified for inclusion in the trial, they were randomly assigned to receive either the test or the control product (Figure 1). The formulation was incorporated in a yogurt drink, and their effect was assessed compared with a control yogurt drink. Over a period of 8 wk, subjects consumed 2 bottles of test product (100 g) with their breakfast. The effect of treatment was measured between 2.5 and 3 h after intake by measuring OBP at baseline (visit days 1, 2, and 3), after 4 wk of intervention (visits day 4 and 5), and at week 8 of intervention (visit days 6, 7, and 8). Before the OBP measurements were made, subjects were weighed. Urine was collected for 24-h at the beginning and end of the study for urinalysis (see below). To calculate the background dairy intake of the subjects, records were kept for 3d(2 weekdays and one weekend day) before randomization and at the end of the intervention. Diet instructions For the duration of the study, subjects were asked to maintain their habitual sodium and dairy intakes and physical activity patterns. They had to refrain from the consumption of nondairy fermented foods, alcohol-containing beverages, or strenuous exercise for 12 h before the test day, which started after an overnight fast. Because of the effect of caffeine on blood pressure,
3 ENZYMATICALLY HYDROLYZED LACTOTRIPEPTIDES AND BLOOD PRESSURE Allocated to enzymatic hydrolyzed LTP 55 Used antihypertensive medication before the study 134 Completed intervention 4603 Completed telephone screening 1383 Answered selection questionnaire 1097 Screened 283 Eligible (=safety population) 275 Randomized (=ITT population) 3220 Excluded criteria (BMI, age) or voluntary withdrawal 286 Excluded criteria (medical history) or voluntary withdrawal 814 Excluded criteria (BP, routine lab analysis) or voluntary withdrawal 8 Lost during baseline criteria (BP) or voluntary withdrawal 139 Allocated to 56 Used antihypertensive medication before the study 137 Completed intervention FIGURE 1. Flow chart showing the selection process, randomization, and dropout rate of the study participants. ITT, intention-to-treat; LTP, Lactotripeptides; BP, blood pressure. only one caffeinated beverage was allowed per test day at breakfast. On the first test day, volunteers recorded what and how much they ate for breakfast and the time of consumption. On the basis of these records, subjects had exactly the same food and drinks on subsequent test days. Test and control products Unilever manufactured both the test and the control product from pasteurized yogurt. The substance added to the test product was a casein hydrolysate powder, enzymatically hydrolyzed by an Aspergillus oryzae protease (Arla Foods, Copenhagen, Denmark). The test product (200 g -enriched yogurt beverage) contained 28.9 mg IPP/L and 22.0 mg VPP/L. The addition of in the test product led to an extra protein and lactic acid content that was corrected for with skim milk powder and a lactic acid solution in the control product. Furthermore, pectin was added for stability and sugar and flavor for taste. Consequently, the nutritional composition of both test products was 13% carbohydrate, 1.5% fat, 3.6% protein, 90mgCa/100g,and141mgK/100g.Bothused(empty)andunused bottles had to be returned to the research center by the volunteers to assess adherence with the product. Blood pressure measurements OBP was taken on 2 (week 4) or 3 (baseline and week 8) consecutive days, while the subjects were in a sitting position, on the left arm after 15 min of rest with an oscillometric automatic device (Omron HEM 907; Omron Healthcare, Inc, Bannockburn, IL). Each measurement was derived from 3 successive readings separated by 30 s. If the difference in SBP between the last 2 measurements was 7 mm Hg, an additional measurement was performed. The mean of the last 2 readings was used for analysis. The first blood pressure measurements of each test day was not used in the statistical analysis of the data, but served the purpose of getting the volunteers accustomed (and thus relaxed) to the measurements. Twenty-four h urinalysis From the 24-h urine sample, 10 ml was used for the measurement of Na,K, microalbumin, and creatinine excretion. Medical Laboratories Stein & Colleagues analyzed all samples in one run after storage of the urine at 20 C. Statistical considerations On the basis of previous experiments, we expected a withinsubject variance in SBP over time of 71 (SD 2 ). Therefore, to demonstrate a decrease in SBP of 3 mm Hg with a power of 90%, 135 subjects were needed in each arm of the study. To allow for dropout, 13 more subjects were recruited. Statistical analysis was performed by using SAS Software (version 9.1; SAS Institute, Cary, NC). Descriptive analyses included distribution statistics (number of available observations, mean, SD) for continuous data. For OBP, the means of all measurements during the consecutive days of each week (4 or 8) were averaged, and change from baseline (week 0) was considered the response variable for the analysis. Data from visits 1, 2, and 3 were averaged for baseline values; those from visit 4 and 5 for the response at 4 wk; and those from visits 6, 7, and 8 for the response at 8 wk of intervention. The effects of treatment on both primary (blood pressure) and secondary outcomes (urinalysis, weight, and background diet) were evaluated for each week (4 or 8) by means of an analysis of covariance, including treatment, subject, and baseline blood pressure in the model. The difference in efficacy between placebo and active ingredient was estimated on the basis of adjusted means. No adjustments were made for multiplicity due to testing multiple(secondary) variables. The secondary analyses were expected to support the primary results. Tests on blood pressure variables were 1-sided, whereas they were 2-sided for the other variables with a significance level of 5%. Finally, we tested a restricted set of prespecified potential confounders on the magnitude of the treatment effect. These included starting cohort, weight change, site, and change in urinary the Na /K excretion ratio (only at week 8). RESULTS We enrolled 283 subjects into this study according to the flow chart in Figure 1. From the intention-to-treat population (ie, all individuals who had been randomly assigned and received at least one dose of the study treatment), 111 subjects had been taking antihypertensive medication in the past 3 mo before the study, but not during the intervention. Four volunteers dropped out during the study intervention; 2 withdrew consent because of personal circumstances (allocated to ) and 2 because their blood pressure increased to levels above the exclusion criteria(allocated to control). The characteristics of the study population at the start of the study are presented in Table 2. The groups were well balanced. Also, estimated adherence to treatment was excellent and comparable between the treatment groups (98% in both groups). Office blood pressure Eight weeks of intervention showed a minor decrease in blood pressure that was not statistically significantly different between
4 1700 VAN DER ZANDER ET AL TABLE 2 Baseline characteristics of study subjects 1 Characteristic (n 76 M, 60 F) (n 77 M, 62 F) Age (y) Body weight (kg) BMI (kg/m 2 ) Plasma lipid profile Total cholesterol (mmol/l) LDL cholesterol (mmol/l) HDL cholesterol (mmol/l) Triglycerides (mmol/l) SBP (mm Hg) DBP (mm Hg) Heart rate (beats/min) Urinary sodium (mmol/24 h) Urinary potassium (mmol/24 h) Dairy protein intake (g/d) Diary calcium intake (mg/d) All values are means SDs., enzymatically hydrolyzed lactotripeptides; SBP, systolic blood pressure; DBP, diastolic blood pressure. None of the differences between the 2 groups were statistically significant. the and control treatments (Table 3). The results of the per-protocol population (n 258), which included only those who adhered to the protocol, displayed similar results (data not shown). In exploratory post hoc confounder analysis, the magnitude of blood pressure lowering was not affected by age, sex, cohort, research site, previous use of antihypertensive medication, BMI, and urinary excretion of sodium and potassium. A posterior power analysis using the actual measured withinsubject variance of 24, showed that the present study had a power of 90% to detect a significant difference of 3 mm Hg between the treatment arms at week 8. TABLE 3 Diet markers and blood pressure during follow-up 1 Measurement (n 136) Body weight, background diet, and adverse events Body weight did not change significantly during the 8-wk study period ( kg in the group compared with kg in the control group; P 0.48). The background diet, as measured by 24-h urinary excretion of sodium and potassium and derived from the diary, also showed no significant changes during the study (Table 3). Adverse events were registered from all of the subjects (n 283) who participated in the study and have been coded according to ICD-9. A total of 169 subjects reported adverse events (AEs). Three serious AEs (hip operation, death after heart failure between screening and the start of the study, and a case of severe hypertension) were reported but were considered to be unrelated to the study. Only 2 AEs (severe hypertension and headache) led to discontinuation of (placebo) treatment. Frequency, intensity, and duration of AEs between treatment groups were not significantly different. The most common complaints were brief periods of upper respiratory tract infections and headache (ICD-9 codes , acute nasopharyngitis, and headache): 49 reports during -milk treatment and 59 reports during placebo treatment. Gastrointestinal AEs (ICD-9 code 787-related, diarrhea, vomiting, pyrosis, etc) were not very common (12 reports in each group). None of the AEs were considered to be related to any of the test products. DISCUSSION The results of the current study in 275 mild hypertensive subjects showed that 10.2 mg /d did not lead to a reduction in OBP compared with placebo. This lack of effect does not seem to result from inadequate intake as estimated adherence with the product in this study was excellent. Nevertheless, we recognize that our method of assessing adherence was rather crude, and that actual adherence may have been lower. Our findings are in contrast with those obtained in several populations, mainly Japanese Week 4 Week 8 (n 139) P value 2 (n 134) (n 137) P value 2 SBP (mm Hg) Change from baseline DBP (mm Hg) Change from baseline Heart rate (beats/min) Change from baseline Diet markers Urinary sodium (mmol/24 h) Change from baseline Urinary potassium (mmol/24 h) Change from baseline Dairy protein intake (g/d) Change from baseline Dairy calcium intake (mg/d) Change from baseline All values are least-squares means SEM (means adjusted for the imbalance in number of subjects and/or the number of observations because of dropouts and/or missing data)., enzymatically hydrolyzed lactotripeptides; SBP, systolic blood pressure; DBP, diastolic blood pressure. 2 P values (ANCOVA) refer to the differences between the 2 study groups at the respective time periods. 3 Significantly different from baseline, P 0.05.
5 ENZYMATICALLY HYDROLYZED LACTOTRIPEPTIDES AND BLOOD PRESSURE 1701 and Finnish (1, 2, 4 7, 10 13, 15). What could explain the discrepancy in results between our study and the others? We studied people who were generally healthy except for elevated blood pressure with sodium, potassium, and dairy intakes representative of the typical Dutch population. The number of subjects would a priori have been sufficient to demonstrate a blood pressure reduction from in this study. The posterior power analysis showed that the study was very well powered. Because the variability in measurements was reduced as much as possible by measuring OBP on several consecutive days, and was comparable with the variability associated with 24-h ambulatory measurements in other studies, the lack of effect was likely due to large individual variability in blood pressure responses to treatment. Nevertheless, we found no difference in the number of responders (based on a lowering of SBP of 3mmHg or the attainment of a SBP 140 mm Hg) between the and placebo treatments. This further supports the conclusion that does not affect blood pressure. From a theoretical point of view, several variables such as baseline blood pressure, race, and background diet were able to modify the response to. It has been suggested that LTPenriched products would have a greater effect in mild-tomoderate hypertensive patients and do not affect blood pressure in normotensive subjects (7, 10, 11). However, this cannot explain the lack of effect in this study, because blood pressure was clearly elevated in our patients (average blood pressure at baseline: 150/86 mm Hg). The potential influence of race and background diet as a cause of a differential effect in Asian and European populations is more difficult to assess. No studies that investigated different ethnicities have been reported. Therefore, it remains speculative why Japanese researchers showed a significant reduction in blood pressure by, whereas this could not be confirmed in European subjects (7, 10). It was observed that mainly small studies showed a large blood pressure lowering effects, whereas large studies showed smaller or no effects, which suggests publication bias. Until now, investigators used 3 different test products containing IPP and VPP in clinical studies: direct fermented milk (1 4, 6, 8, 9, 12 15), FLTP (5, 11), and powder (7, 10). Direct fermented milk has been investigated in most of the studies and resulted in an average decrease of 8 mm Hg SBP. Powdered fermented milk and powdered enzymatically hydrolyzed casein have been less well studied, but seemed to generate smaller effects on SBP: decreases of 6 and 3 mm Hg for FLTP and, respectively. These results have led to the speculation that a specific production route is important to the generation of LTP-induced blood pressure lowering effects; therefore, does not affect blood pressure or at least exploits rather modest effects compared with fermented products. However, it is unknown whether the smaller SBP decreases observed were due to the lower number of subjects that have been studied so far or that is indeed less effective than fermented products. Because fermented milk products at a similar LTP level have different (bioactive) peptide profiles, these products could theoretically generate a larger drop in blood pressure than. However, further research on fermented products or a head-to-head comparison of different LTP production routes on blood pressure reduction is needed to confirm this hypothesis. Foltz et al (19) recently confirmed that IPP is able to enter the blood circulation undegraded after oral ingestion of an enriched yogurt beverage. Although the acute oral bolus of LTP in that study is 5 times that in the current study, the maximum levels of IPP were observed min after intake of the -enriched beverage and min after intake of the control product. This raises the question of whether a reduction in blood pressure could be observed between 2.5 and 3 h after intake in this study. In contrast, however, Jauhiainen et al (15) observed a significant fall in 24-h ambulatory blood pressure after consumption of fermented milk for 10 wk. This could suggest that fermented milk is indeed more potent at reducing blood pressure than is. However, there may be more bioactives present in fermented milk products than in IPP alone, which could contribute to the effect over 24 h. A study that investigated the development of hypertension in spontaneously hypertensive rats indicated that intake of fermented milk indeed attenuated high blood pressure more effectively than did pure synthetically produced LTP or pure LTP combined with minerals (20). In conclusion, this study showed no effect of an -enriched yogurt beverage on the blood pressure of hypertensive subjects. We thank Peter Holleman, Linda van Osch, Inge Verkooijen, and Frans Thomassen for their substantive contributions to the study conduct. The authors responsibilities were as follows KvdZ: designed the study, monitored the study conduct, analyzed and interpreted the data, and wrote the manuscript; MLB: provided significant advice and consultation, critically evaluated the manuscript, and collected, analyzed, and interpreted the data; AAAB (Principle Investigator at the Utrecht/Amersfoort site and study physician): designed the study, provided significant advice and consultation, and critically evaluated the manuscript; MMGK: designed the study, monitored the study conduct, interpreted the data, and critically evaluated the manuscript; PWdL (Principle Investigator at the Maastricht site and study physician): designed the study, provided significant advice and consultation, interpreted the data, and critically evaluated the manuscript; and MLB, AAAB, and PWdL: had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. The sponsor monitored the study, but was not involved in on-site data collection, data analysis, or data interpretation. KvdZ and MMGK are employees of the Unilever Food & Health Research Institute, Vlaardingen, Netherlands. No conflicts of interest were declared by the other authors. REFERENCES 1. Hata Y, Yamamoto M, Ohni M, Nakajima K, Nakamura Y, Takano T. A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am J Clin Nutr 1996;64: Hirata H, Nakamura Y, Yada H, Moriguchi S, Kajimoto O, Takahashi T. Clinical effects of new sour milk drink on mild or moderate hypertensive subjects. J New Rem Clin 2002;51: Itakura H, Ikemoto S, Terada S, Kondo K. The effect of sour milk on blood pressure in untreated hypertensive and normotensive subjects. J Jap Soc Clin Nutr 2001;23: Kajimoto O, Nakamura Y, Yada H, Moriguchi S, Hirata H, Takahashi T. Hypotensive effects of sour milk in subjects with mild or moderate hypertension. J Jap Soc Nutr Food Sci 2001;54: Kajimoto O, Aihara K, Hirata H, Takahashi R, Nakamura Y. Hypotensive effects of the tablets containing Lactotripeptides (VPP,IPP). J Nutr Food 2001;4: Kajimoto O, Kurosaki T, Mizutani J, et al. Antihypertensive effects of liquid yoghurts containing lactotripeptides (VPP,IPP) in mild hypertensive subjects. J Nutr Food 2002;5: Mizuno S, Matsuura K, Gotou T, et al. Antihypertensive effect of casein hydrolyzate prepared using an Aspergillus oryzae protease in a placebocontrolled clinical study for subjects with high-normal blood pressure and mild-hypertension. Br J Nutr 2005;94: Mizushima S, Ohshige K, Watanabe J, et al. Randomized controlled trial of sour milk on blood pressure in borderline hypertensive men. Am.J. Hypertens 2004;17: Nakamura Y, Kajimoto O, Kaneko K, et al. Effects of the liquid yoghurts
6 1702 VAN DER ZANDER ET AL containing lactotripeptides (VPP,IPP) on high-normal blood pressure. J Nutr Food 2004;7: Sano J, Ohki K, Higuchi T, et al. Effect of casein hydrolysate, prepared with protease derived from Aspergillus oryzae, on subjects with highnormal blood pressure or mild hypertension. J Med Food 2005;8: Aihara K, Kajimoto O, Hirata H, Takahashi R, Nakamura Y. Effect of powdered fermented milk with Lactobacillus helveticus on subjects with high-normal blood pressure or mild hypertension. J Am Coll Nutr 2005; 24: Seppo L, Kerojoki O, Suomalainen T, Korpela R. The effect of a Lactobacillus helveticus LBK-16 H fermented milk on hypertension a pilot study on humans. Milchwissenschaft 2002;57: Seppo L, Jauhiainen T, Poussa T, Korpela R. A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects. Am J Clin Nutr 2003;77: Tuomilehto J, Lindstrom J, Hyyrynen J, et al. Effect of ingesting sour milk fermented using Lactobacillus helveticus bacteria producing tripeptides on blood pressure in subjects with mild hypertension. J Hum Hypertens 2004;18: Jauhiainen T, Vapaatalo H, Poussa T, Kyronpalo S, Rasmussen M, Korpela R. Lactobacillus helveticus fermented milk lowers blood pressure in hypertensive subjects in 24-h ambulatory blood pressure measurement Am J Hypertens 2005;18: Matsuura K, Mizuno S, Nishimura S, Gotou T, Yamamoto N. Quantitative analysis of antihypertensive peptides, Val-Pro-Pro and Ile-Pro- Pro, in casein hydrolyzate with Aspergillus oryzae protease by a LC-MS method. Milchwissenschaft 2004;60: Mizuno S, Nishimura S, Matsuura K, Gotou T, Yamamoto N. Release of short and proline-rich antihypertensive peptides from casein hydrolysate with an Aspergillus oryzae protease. J Dairy Sci 2004;87: Engberink MF, Schouten EG, Kok FJ, van Mierlo LA, Brouwer IA, Geleijnse JM. Lactotripeptides show no effect on human blood pressure: results from a double-blind randomized controlled trial. Hypertension 2008;51: Foltz M, Meynen EE, Bianco V, van Platerink C, Koning TM, Kloek J. Angiotensin converting enzyme inhibitory peptides from a lactotripeptideenriched milk beverage are absorbed intact into the circulation. J Nutr 2007; 137: Jauhiainen T, Collin M, Narva M, et al. Effect of long-term intake of milk peptides and minerals on blood pressure and arterial function in spontaneously hypertensive rats. Milchwissenschaft 2005;60:
Lactotripeptides Show No Effect on Human Blood Pressure Results From a Double-Blind Randomized Controlled Trial
Lactotripeptides Show No Effect on Human Blood Pressure Results From a Double-Blind Randomized Controlled Trial Mariëlle F. Engberink, Evert G. Schouten, Frans J. Kok, Linda A.J. van Mierlo, Ingeborg A.
More informationSCIENTIFIC OPINION. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) 2. European Food Safety Authority (EFSA), Parma, Italy
SCIENTIFIC OPINION Scientific Opinion on the substantiation of health claims related to isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) and maintenance of normal blood pressure (ID 615,
More informationBritish Journal of Nutrition
(2009), 101, 776 786 q The Authors 2008 doi:10.1017/s0007114508137722 Review Article Lactotripeptides and antihypertensive effects: a critical review Esther Boelsma 1 * and Joris Kloek 2 1 TNO Quality
More informationA fermented milk high in bioactive peptides has a blood pressure lowering effect in hypertensive subjects 1 3
A fermented milk high in bioactive peptides has a blood pressure lowering effect in hypertensive subjects 1 3 Leena Seppo, Tiina Jauhiainen, Tuija Poussa, and Riitta Korpela ABSTRACT Background: Angiotensin-converting
More informationEFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on
Downloaded from orbit.dtu.dk on: Feb 01, 2018 EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to isoleucyl-prolyl-proline
More informationThe milk protein-derived biologically active peptides
AJH 2005; 18:1600 1605 Lactobacillus helveticus Fermented Milk Lowers Blood Pressure in Hypertensive Subjects in 24-h Ambulatory Blood Pressure Measurement Tiina Jauhiainen, Heikki Vapaatalo, Tuija Poussa,
More informationClinical Trial Synopsis TL-OPI-525, NCT#
Clinical Trial Synopsis, NCT#00762736 Title of Study: A Phase II, Double-Blind, Randomized, Placebo-Controlled, Proof-of-Concept Study of the Efficacy, Safety, and Tolerability of Pioglitazone HCl (ACTOS
More informationPFIZER INC. THERAPEUTIC AREA AND FDA APPROVED INDICATIONS: See USPI.
PFIZER INC. These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved package insert. For publications based on this study, see associated bibliography.
More informationClinical Study Synopsis
Clinical Study Synopsis This Clinical Study Synopsis is provided for patients and healthcare professionals to increase the transparency of Bayer's clinical research. This document is not intended to replace
More informationInstitute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland 2
Nutrition and Metabolism Volume 2010, Article ID 287030, 6 pages doi:10.1155/2010/287030 Research Article Milk Products Containing Bioactive Tripeptides Have an Antihypertensive Effect in Double Transgenic
More informationRandomized double-blind controlled clinical trial of the blood pressure lowering effect of fermented milk with Lactococcus lactis: A pilot study 1,2
J. Dairy Sci. 101:1 7 https://doi.org/10.3168/jds.2017-13189 American Dairy Science Association, 2018. Randomized double-blind controlled clinical trial of the blood pressure lowering effect of fermented
More informationNew Hypertension Guideline Recommendations for Adults July 7, :45-9:30am
Advances in Cardiovascular Disease 30 th Annual Convention and Reunion UERM-CMAA, Inc. Annual Convention and Scientific Meeting July 5-8, 2018 New Hypertension Guideline Recommendations for Adults July
More informationClinical Trial Synopsis TL-OPI-518, NCT#
Clinical Trial Synopsis, NCT# 00225264 Title of Study: A Double-Blind, Randomized, Comparator-Controlled Study in Subjects With Type 2 Diabetes Mellitus Comparing the Effects of Pioglitazone HCl vs Glimepiride
More informationSYNOPSIS 2/198 CSR_BDY-EFC5825-EN-E02. Name of company: TABULAR FORMAT (For National Authority Use only)
SYNOPSIS Title of the study: A randomized, double-blind, placebo-controlled, parallel-group, fixed-dose (rimonabant 20 mg) multicenter study of long-term glycemic control with rimonabant in treatment-naïve
More informationSYNOPSIS. Publications No publications at the time of writing this report.
Drug product: TOPROL-XL Drug substance(s): Metoprolol succinate Study code: D4020C00033 (307A) Date: 8 February 2006 SYNOPSIS Dose Ranging, Safety and Tolerability of TOPROL-XL (metoprolol succinate) Extended-release
More informationSponsor Novartis. Generic Drug Name Vildagliptin/Metformin. Therapeutic Area of Trial Type 2 diabetes. Approved Indication Type 2 diabetes
Clinical Trial Results Database Page 1 Sponsor Novartis Generic Drug Name Vildagliptin/Metformin Therapeutic Area of Trial Type 2 diabetes Approved Indication Type 2 diabetes Study Number CLMF237A2309
More informationHigh-dose monotherapy vs low-dose combination therapy of calcium channel blockers and angiotensin receptor blockers in mild to moderate hypertension
(2005) 19, 491 496 & 2005 Nature Publishing Group All rights reserved 0950-9240/05 $30.00 www.nature.com/jhh ORIGINAL ARTICLE High-dose monotherapy vs low-dose combination therapy of calcium channel blockers
More informationThe impact of milk proteins and peptides on blood pressure and vascular function: a review of evidence from human intervention studies
, page 1 of 14 q The Authors 2013 doi:10.1017/s0954422413000139 The impact of milk proteins and peptides on blood pressure and vascular function: a review of evidence from human intervention studies Ágnes
More informationSupplementary Online Content
Supplementary Online Content Larsen JR, Vedtofte L, Jakobsen MSL, et al. Effect of liraglutide treatment on prediabetes and overweight or obesity in clozapine- or olanzapine-treated patients with schizophrenia
More informationLong-term intervention with Lactobacillus helveticus fermented milk reduces augmentation index in hypertensive subjects
(21) 64, 424 431 & 21 Macmillan Publishers Limited All rights reserved 954-37/1 $32. www.nature.com/ejcn EJCN Open ORIGINAL ARTICLE Long-term intervention with Lactobacillus helveticus fermented milk reduces
More informationManaging High Blood Pressure Naturally. Michael A. Smith, MD Life Extension s Healthy Talk Series
Managing High Blood Pressure Naturally Michael A. Smith, MD Life Extension s Healthy Talk Series Part 1 What is Blood Pressure? Blood Pressure Systole Systolic Forward Pressure 110 mmhg 70 mmhg Diastole
More informationAntihypertensive Trial Design ALLHAT
1 U.S. Department of Health and Human Services Major Outcomes in High Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic National Institutes
More informationThe clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only.
The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. Please note that the results reported in any single trial may not reflect the overall
More informationUsing the New Hypertension Guidelines
Using the New Hypertension Guidelines Kamal Henderson, MD Department of Cardiology, Preventive Medicine, University of North Carolina School of Medicine Kotchen TA. Historical trends and milestones in
More informationStudy Code: Date: 27 July 2007
These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved package insert in the country of prescription Sponsor/company: Generic drug name:
More informationSoy Protein. Muscle health benefits: for Sports Nutrition Recovery and during aging. May 9, Mark Cope, PhD
Soy Protein Muscle health benefits: for Sports Nutrition Recovery and during aging May 9, 2017 Mark Cope, PhD Blending Proteins to Provide Better Muscle Health Importance of Muscle Health The Benefits
More informationClinical Trial Results Database Page 1
Clinical Trial Results Database Page 1 Sponsor Novartis Pharmaceuticals Corporation Generic Drug Name Therapeutic Area of Trial Major Depressive Disorder (MDD) Approved Indication Treatment of major depressive
More informationRole of Minerals in Hypertension
Role of Minerals in Hypertension Lecture objectives By the end of the lecture students will be able to Define primary and secondary hypertention and their risk factors. Relate role of minerals with hypertention.
More informationSUPPLEMENTARY DATA. Supplementary Table 1. Baseline Patient Characteristics
Supplementary Table 1. Baseline Patient Characteristics Normally distributed data are presented as mean (±SD), data that were not of a normal distribution are presented as median (ICR). The baseline characteristics
More informationHypertension Clinical case scenarios for primary care
Hypertension Clinical case scenarios for primary care Implementing NICE guidance August 2011 NICE clinical guideline 127 What this presentation covers Five clinical case scenarios, including: presentation
More informationSession 39 I. Politis Agricultural University of Athens
Session 39 Email: i.politis@aua.gr I. Politis Agricultural University of Athens i.politis@aua.gr Opioid Antihypertensive Antithrombotic Immunoregulatory Enhancement or Suppression? Origin of immunoregulatory
More informationTreatment A Placebo to match COREG CR 20 mg OD + Lisinopril 10 mg OD (Days 1-7) Placebo to match COREG CR 40 mg OD + Lisinopril 10 mg OD (Days 8-14)
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More informationObesity Prevention and Control: Provider Education with Patient Intervention
Obesity Prevention and : Provider Education with Patient Summary Evidence Table and Population Cohen et al. (1991) 1987-1988 : RCT Location: Pittsburgh, PA Physician training session by a behavioral psychologist
More informationHealth Benefits of Lowering Sodium Intake in the US
Health Benefits of Lowering Sodium Intake in the US Lawrence J Appel, MD, MPH Professor of Medicine, Epidemiology and International Health (Human Nutrition) Director, Welch Center for Prevention, Epidemiology
More informationThe role of physical activity in the prevention and management of hypertension and obesity
The 1 st World Congress on Controversies in Obesity, Diabetes and Hypertension (CODHy) Berlin, October 26-29 2005 The role of physical activity in the prevention and management of hypertension and obesity
More informationprogramme. The DE-PLAN follow up.
What are the long term results and determinants of outcomes in primary health care diabetes prevention programme. The DE-PLAN follow up. Aleksandra Gilis-Januszewska, Noël C Barengo, Jaana Lindström, Ewa
More informationMilk Peptides and Blood Pressure 1,2
The Journal of Nutrition Effects of Probiotics and Prebiotics Milk Peptides and Blood Pressure 1,2 Tiina Jauhiainen 3,4 and Riitta Korpela 3 5 * 3 Valio Ltd., Research Center, Helsinki, Finland; 4 Institute
More informationRICHMOND PARK SCHOOL LIFESTYLE SCREENING REPORT Carmarthenshire County Council
RICHMOND PARK SCHOOL LIFESTYLE SCREENING REPORT 2016 Carmarthenshire County Council WHY LEAD A HEALTHY LIFESTYLE? A nutritious, well-balanced diet along with physical activity and refraining from smoking
More information5.2 Key priorities for implementation
5.2 Key priorities for implementation From the full set of recommendations, the GDG selected ten key priorities for implementation. The criteria used for selecting these recommendations are listed in detail
More informationThe 2015 Dutch food-based dietary guidelines:
The 2015 Dutch food-based dietary guidelines: supplementary information Appendix 1: explanation of how the Health Council of the Netherlands has handled interests of the committee. Appendix 2: 17 supplementary
More informationKnow Your Numbers Blood Pressure Cholesterol Blood Sugar
Know Your Numbers Blood Pressure Cholesterol Blood Sugar 2015 Wellness Warriors Sponsored by: Wayne State University Presented by: Debbie Cavender, RDN STRATEGIC WELLNESS, LLC The information in this presentation
More informationDairy matrix effects on T2 diabetes and cardiometabolic health?
Department of Nutrition, Exercise and Sports Dairy matrix effects on T2 diabetes and cardiometabolic health? Arne Astrup Head of department, professor, MD, DMSc. Department of Nutrition, Exercise and Sports
More informationValidation of the SEJOY BP-1307 upper arm blood pressure monitor for home. blood pressure monitoring according to the European Society of Hypertension
Validation of the SEJOY BP-1307 upper arm blood pressure monitor for home blood pressure monitoring according to the European Society of Hypertension International Protocol revision 2010 Short title: Validation
More informationBRIEF COMMUNICATIONS. KEY WORDS: Ambulatory blood pressure monitoring, placebo effect, antihypertensive drug trials.
AJH 1995; 8:311-315 BRIEF COMMUNICATIONS Lack of Placebo Effect on Ambulatory Blood Pressure Giuseppe Mancia, Stefano Omboni, Gianfranco Parati, Antonella Ravogli, Alessandra Villani, and Alberto Zanchetti
More informationSCIENTIFIC STUDY REPORT
PAGE 1 18-NOV-2016 SCIENTIFIC STUDY REPORT Study Title: Real-Life Effectiveness and Care Patterns of Diabetes Management The RECAP-DM Study 1 EXECUTIVE SUMMARY Introduction: Despite the well-established
More information2.0 Synopsis. Choline fenofibrate capsules (ABT-335) M Clinical Study Report R&D/06/772. (For National Authority Use Only) Name of Study Drug:
2.0 Synopsis Abbott Laboratories Individual Study Table Referring to Part of Dossier: (For National Authority Use Only) Name of Study Drug: Volume: Choline Fenofibrate (335) Name of Active Ingredient:
More informationPublished in: NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES. DOI: /j.numecd Document Version Peer reviewed version
The effect of yoghurt and its probiotics on blood pressure and serum lipid profile; a randomised controlled trial. Ivey, K., Hodgson, J., Kerr, D. A., Thompson, P., Stojceski, B., & Prince, R. (2015).
More informationNext generation pre, pro, and synbiotics
LP-LDL : Cholesterol & hypertension reduction Next generation pre, pro, and synbiotics Prevention Management Treatment February 2017 Stephen OHara Chief Executive Officer 1 Company Overview Founded in
More informationTENSIDYSS. Blood pressure regulator. Marine Ingredients developer for high health benefits
Marine Ingredients developer for high health benefits TENSIDYSS Blood pressure regulator MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS CONTENTS
More informationThis study may not be disseminated, reproduced in whole or in part without the written permission of Roduve Healthcare Solutions.
This study may not be disseminated, reproduced in whole or in part without the written permission of Roduve Healthcare Solutions. A Randomized Controlled Trial for Roduve Healthcare Solutions on the Efficacy
More informationThe effect of a change in ambient temperature on blood pressure in normotensives
(2001) 15, 113 117 2001 Nature Publishing Group All rights reserved 0950-9240/01 $15.00 www.nature.com/jhh ORIGINAL ARTICLE The effect of a change in ambient temperature on blood pressure in normotensives
More informationCONCORD INTERNAL MEDICINE HYPERTENSION PROTOCOL
CONCORD INTERNAL MEDICINE HYPERTENSION PROTOCOL Douglas G. Kelling Jr., MD Carmella Gismondi-Eagan, MD, FACP George C. Monroe, III, MD Revised, April 8, 2012 The information contained in this protocol
More informationThe clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only.
The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. Please note that the results reported in any single trial may not reflect the overall
More informationSupplementary Online Content. Abed HS, Wittert GA, Leong DP, et al. Effect of weight reduction and
1 Supplementary Online Content 2 3 4 5 6 Abed HS, Wittert GA, Leong DP, et al. Effect of weight reduction and cardiometabolic risk factor management on sympton burden and severity in patients with atrial
More informationThe Indian Polycap Study 1 & 2 (TIPS 1 & 2) and The International Polycap Study 3 & 4 (TIPS 3 & 4)
The Indian Polycap Study 1 & 2 (TIPS 1 & 2) and The International Polycap Study 3 & 4 (TIPS 3 & 4) Denis Xavier MD, MSc Professor and Head, Pharmacology, St. John's Medical College Coordinator, Division
More informationPrimary Outcome Results of DiRECT the Diabetes REmission Clinical Trial
Finding a practical management solution for T2DM, in primary care Primary Outcome Results of DiRECT the Diabetes REmission Clinical Trial Mike Lean, Roy Taylor, and the DiRECT Team IDF Abu Dhabi, December
More informationDairy consumption and cardiometabolic health do the trials support the epidemiology?
Dairy consumption and cardiometabolic health do the trials support the epidemiology? Karen Murphy, PhD RNutr & Georgina Crichton Food Industry Forum, 31 st August 2010 Dairy Australians are eating 1-1.5
More informationThe clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only.
The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. Please note that the results reported in any single trial may not reflect the overall
More informationHYPERTENSION: ARE WE GOING TOO LOW?
HYPERTENSION: ARE WE GOING TOO LOW? George L. Bakris, M.D.,F.A.S.N.,F.A.S.H., F.A.H.A. Professor of Medicine Director, ASH Comprehensive Hypertension Center University of Chicago Medicine Chicago, IL USA
More informationBritish Journal of Nutrition
(2011), 105, 118 122 doi:10.1017/s000711451000317x q The Authors 2010. The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons
More informationAmerican Diabetes Association: Standards of Medical Care in Diabetes 2015
American Diabetes Association: Standards of Medical Care in Diabetes 2015 Synopsis of ADA standards relevant to the 11 th Scope of Work under Task B.2 ASSESSMENT OF GLYCEMIC CONTROL Recommendations: Perform
More informationAntihypertensive Peptides from Milk Proteins
Pharmaceuticals 2010, 3, 251-272; doi:10.3390/ph3010251 Review OPEN ACCESS pharmaceuticals ISSN 1424-8247 www.mdpi.com/journal/pharmaceuticals Antihypertensive Peptides from Milk Proteins Pauliina Jäkälä
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and
More informationSponsor. Generic drug name. Trial indication(s) Protocol number. Protocol title. Phase of Drug Development. Study Start/End Dates
Sponsor Novartis Generic drug name SAB378 [Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone] Trial indication(s) Postherpetic neuralgia (PHN) Protocol number CSAB378A2201 Protocol title A multicenter,
More informationCardiac Pathophysiology
Cardiac Pathophysiology Evaluation Components Medical history Physical examination Routine laboratory tests Optional tests Medical History Duration and classification of hypertension. Patient history of
More informationFrom the desk of the: THE VIRTUAL NEPHROLOGIST
Hypertension, also referred to as high blood pressure or HTN, is a medical condition in which the blood pressure is chronically elevated. It is a very common illness. One out of three American adults has
More informationTraditional Asian Soyfoods. Proven and Proposed Cardiovascular Benefits of Soyfoods. Reduction (%) in CHD Mortality in Eastern Finland ( )
Proven and Proposed Cardiovascular Benefits of Soyfoods Mark Messina, PhD, MS Soy Nutrition Institute Loma Linda University Nutrition Matters, Inc. markjohnmessina@gmail.com 1000 80 20 60 40 40 60 20 80
More informationORIGINAL INVESTIGATION. C-Reactive Protein Concentration and Incident Hypertension in Young Adults
ORIGINAL INVESTIGATION C-Reactive Protein Concentration and Incident Hypertension in Young Adults The CARDIA Study Susan G. Lakoski, MD, MS; David M. Herrington, MD, MHS; David M. Siscovick, MD, MPH; Stephen
More informationClinical Study Synopsis
Clinical Study Synopsis This Clinical Study Synopsis is provided for patients and healthcare professionals to increase the transparency of Bayer's clinical research. This document is not intended to replace
More informationScreening Results. Juniata College. Juniata College. Screening Results. October 11, October 12, 2016
Juniata College Screening Results Juniata College Screening Results October 11, 2016 & October 12, 2016 JUNIATA COLLEGE The J.C. Blair Hospital CARES team screened 55 Juniata College employees on October
More informationIndividual Study Table Referring to Item of the Submission: Volume: Page:
2.0 Synopsis Name of Company: Abbott Laboratories Name of Study Drug: Meridia Name of Active Ingredient: Sibutramine hydrochloride monohydrate Individual Study Table Referring to Item of the Submission:
More informationSYNOPSIS OF RESEARCH REPORT (PROTOCOL BC20779)
TITLE OF THE STUDY / REPORT No. / DATE OF REPORT INVESTIGATORS / CENTERS AND COUNTRIES Clinical Study Report Protocol BC20779: Multicenter, double-blind, randomized, placebo-controlled, dose ranging phase
More informationYounger adults with a family history of premature artherosclerotic disease should have their cardiovascular risk factors measured.
Appendix 2A - Guidance on Management of Hypertension Measurement of blood pressure All adults from 40 years should have blood pressure measured as part of opportunistic cardiovascular risk assessment.
More informationIndividual Study Table Referring to Part of Dossier: Volume: Page:
Synopsis Abbott Laboratories Name of Study Drug: Paricalcitol Capsules (ABT-358) (Zemplar ) Name of Active Ingredient: Paricalcitol Individual Study Table Referring to Part of Dossier: Volume: Page: (For
More informationTodd S. Perlstein, MD FIFTH ANNUAL SYMPOSIUM
Todd S. Perlstein, MD FIFTH ANNUAL SYMPOSIUM Faculty Disclosure I have no financial interest to disclose No off-label use of medications will be discussed FIFTH ANNUAL SYMPOSIUM Recognize changes between
More informationHypertension: JNC-7. Southern California University of Health Sciences Physician Assistant Program
Hypertension: JNC-7 Southern California University of Health Sciences Physician Assistant Program Management and Treatment of Hypertension April 17, 2018, presented by Ezra Levy, Pharm.D.! Reference Card
More informationHow Low Do We Go? Update on Hypertension
How Low Do We Go? Update on Beth L. Abramson, MD, FRCPC, FACC As presented at the University of Toronto s Saturday at the University Session (September 2003) Arecent World Health Organization report states
More informationPhase 3 investigation of aprocitentan for resistant hypertension management. Investor Webcast June 2018
Phase 3 investigation of aprocitentan for resistant hypertension management Investor Webcast June 2018 The following information contains certain forward-looking statements, relating to the company s business,
More informationWhat s In the New Hypertension Guidelines?
American College of Physicians Ohio/Air Force Chapters 2018 Scientific Meeting Columbus, OH October 5, 2018 What s In the New Hypertension Guidelines? Max C. Reif, MD, FACP Objectives: At the end of the
More informationAngiotensin-converting enzyme inhibitory effects of dairy- and soy-derived peptides in pre-hypertensive overweight men and women
Functional Foods in Health and Disease 2013, 3(1):37-47 Page 37 of 47 Short Report Open Access Angiotensin-converting enzyme inhibitory effects of dairy- and soy-derived peptides in pre-hypertensive overweight
More informationIndividual Study Table Referring to Part of the Dossier. Use only) Name of Finished Product:
SYNOPSIS Fresenius Title of the study: A double-blind, randomized study comparing the safety and torelance of SMOFlipid 20% and Intralipid 20% in long-term treatment with parenteral nutrition Coordinating
More informationEfficacy/pharmacodynamics: 85 Safety: 89
These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved package insert in the country of prescription. Sponsor/Company: Sanofi Drug substance:
More informationLONG-TERM INTAKE OF MILK PEPTIDES ATTENUATES DEVELOPMENT OF HYPERTENSION IN SPONTANEOUSLY HYPERTENSIVE RATS
JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2001, 52, 4, 745 754 www.jpp.krakow.pl M. SIPOLA 1), P. FINCKENBERG 1), J. SANTISTEBAN 1), R. KORPELA 2), H. VAPAATALO 1), M.-L. NURMINEN 1) LONG-TERM INTAKE OF MILK
More informationBlood Pressure Measurement in SPRINT
Blood Pressure Measurement in SPRINT Karen C. Johnson, MD, MPH, FAHA Vice Chair, SPRINT Steering Committee University of Tennessee Health Science Center, Department of Preventive Medicine For the SPRINT
More informationRelation between the angiotensinogen (AGT) M235T gene polymorphism and blood pressure in a large, homogeneous study population
(2003) 17, 555 559 & 2003 Nature Publishing Group All rights reserved 0950-9240/03 $25.00 www.nature.com/jhh ORIGINAL ARTICLE Relation between the angiotensinogen (AGT) M235T gene polymorphism and blood
More informationStudy No.: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable:
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More informationStudy No.:MPX Title: Rationale: Phase: IIB Study Period: Study Design: Centres: Indication: Treatment: Objectives:
The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.
More informationhydrochlorothiazide in the treatment of moderate arterial
Br. J. clin. Pharmac. (1987), 23, 65S-69S Determination of the optimal dosage regimen of captopril + hydrochlorothiazide in the treatment of moderate arterial hypertension D. STERU1, M. CHILDS', S. LANCRENON',
More informationProject Summary: Draft Proposal Continued RESULTS. on the DASH Diet and 30 of the 40 original subjects on the Pro-DASH Diet.
Project Summary: Draft Proposal Continued RESULTS Subjects The HNFE 3034 Spring 2013 semester s research study included 34 of the 38 original subjects on the DASH Diet and 30 of the 40 original subjects
More informationMANAGEMENT OF HYPERTENSION IN PREGNANCY, THE ALGORHITHM
MANAGEMENT OF HYPERTENSION IN PREGNANCY, THE ALGORHITHM Are Particular Anti-hypertensives More Effective or Harmful Than Others in Hypertension in Pregnancy? Existing data is inadequate Methyldopa and
More informationModule 2. Global Cardiovascular Risk Assessment and Reduction in Women with Hypertension
Module 2 Global Cardiovascular Risk Assessment and Reduction in Women with Hypertension 1 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored,
More informationINDIVIDUAL STUDY TABLE REFERRING TO PART OF THE DOSSIER Volume: Page:
SYNOPSIS Protocol No.: TOPMAT-MIG-303 EudraCT No.: 2005-000321-29 Title of Study: A double-blind, randomised, placebo-controlled, multicentre study to investigate the efficacy and tolerability of in prolonged
More informationFructose, Uric Acid and Hypertension in Children and Adolescents
Fructose, Uric Acid and Hypertension in Children and Adolescents Daniel I. Feig, MD, PhD, MS Director, Division of Nephrology Department of Pediatrics University of Alabama, Birmingham Topics for Discussion
More informationSodium and potassium intake and risk of cardiovascular events and all-cause mortality: the Rotterdam Study
Eur J Epidemiol (2007) 22:763 770 DOI 10.1007/s10654-007-9186-2 CARDIOVASCULAR DISEASE Sodium and potassium intake and risk of cardiovascular events and all-cause mortality: the Rotterdam Study Johanna
More informationNew Hypertension Guidelines. Kofi Osei, MD
New Hypertension Guidelines Kofi Osei, MD None Disclosures Objectives The new blood pressure definitions and cardiovascular risk The role to time and location in the diagnosis of hypertension Apply evidence-based
More informationReport Operation Heart to Heart
Report Operation Heart to Heart Elkhorn Logan Valley Public Health Department (Burt, Cuming, Madison, and Stanton Counties) Gina Uhing, Health Director Ionia Research Newcastle, Nebraska Joseph Nitzke
More informationWeight Loss for Young Women - What Works?
Weight Loss for Young Women - What Works? Helen O Connor PhD APD 1 Research Team Hayley Griffin PhD APD 1, Hoi Lun Cheng APD 1, Kieron Rooney PhD 1, Prof Kate Steinbeck MBBS FRACP 2 1. Exercise & Sport
More informationClinical Studies 129
Clinical Studies 129 Syncope in migraine. The population-based CAMERA study Roland D. Thijs, 1* Mark C. Kruit, 2* Mark A. van Buchem, 2 Michel D. Ferrari, 1 Lenore J. Launer, 3,4 and J. Gert van Dijk
More informationANTIHYPERTENSIVE DRUG THERAPY IN CONSIDERATION OF CIRCADIAN BLOOD PRESSURE VARIATION*
Progress in Clinical Medicine 1 ANTIHYPERTENSIVE DRUG THERAPY IN CONSIDERATION OF CIRCADIAN BLOOD PRESSURE VARIATION* Keishi ABE** Asian Med. J. 44(2): 83 90, 2001 Abstract: J-MUBA was a large-scale clinical
More informationMolecular docking study of tripeptides VPP and IPP inhibiting angiotensin I converting enzyme to alleviate high altitude pulmonary edema
International Journal of Genetics and Molecular Biology Vol. 3(1), pp. 1-6, January 2011 Available online at http://www.academicjournals.org/ijgmb ISSN 2006-9863 2011 Academic Journals Full Length Research
More information