National Institute of Integrative Medicine

Melbourne, Australia

National Institute of Integrative Medicine

Melbourne, Australia
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Ried K.,National Institute of Integrative Medicine | Ried K.,University of Adelaide | Fakler P.,University of Adelaide | Stocks N.P.,University of Adelaide
Cochrane Database of Systematic Reviews | Year: 2017

Background: High blood pressure is an important risk factor for cardiovascular disease, contributing to about 50% of cardiovascular events worldwide and 37% of cardiovascular-related deaths in Western populations. Epidemiological studies suggest that cocoa-rich products reduce the risk of cardiovascular disease. Flavanols found in cocoa have been shown to increase the formation of endothelial nitric oxide which promotes vasodilation and therefore blood pressure reduction. Here we update previous meta-analyses on the effect of cocoa on blood pressure. Objectives: To assess the effects on blood pressure of chocolate or cocoa products versus low-flavanol products or placebo in adults with or without hypertension when consumed for two weeks or longer. Search methods: This is an updated version of the review initially published in 2012. In this updated version, we searched the following electronic databases from inception to November 2016: Cochrane Hypertension Group Specialised Register, CENTRAL, MEDLINE and Embase. We also searched international trial registries, and the reference lists of review articles and included trials. Selection criteria: Randomised controlled trials (RCTs) investigating the effects of chocolate or cocoa products on systolic and diastolic blood pressure in adults for a minimum of two weeks duration. Data collection and analysis: Two review authors independently extracted data and assessed the risks of bias in each trial. We conducted random-effects meta-analyses on the included studies using Review Manager 5. We explored heterogeneity with subgroup analyses by baseline blood pressure, flavanol content of control group, blinding, age and duration. Sensitivity analyses explored the influence of unusual study design. Main results: Thirty-five trials (including 40 treatment comparisons) met the inclusion criteria. Of these, we added 17 trials (20 treatment comparisons) to the 18 trials (20 treatment comparisons) in the previous version of this updated review. Trials provided participants with 30 to 1218 mg of flavanols (mean = 670 mg) in 1.4 to 105 grams of cocoa products per day in the active intervention group. The control group received either a flavanol-free product (n = 26 treatment comparisons) or a low-flavanol-containing cocoa powder (range 6.4 to 88 mg flavanols (mean = 55 mg, 13 treatment comparisons; 259 mg, 1 trial). Meta-analyses of the 40 treatment comparisons involving 1804 mainly healthy participants revealed a small but statistically significant blood pressure-reducing effect of flavanol-rich cocoa products compared with control in trials of two to 18 weeks duration (mean nine weeks):Mean difference systolic blood pressure (SBP) (95% confidence interval (CI): -1.76 (-3.09 to -0.43) mmHg, P = 0.009, n = 40 treatment comparisons, 1804 participants;Mean difference diastolic blood pressure (DBP) (95% CI): -1.76 (-2.57 to -0.94) mmHg, P < 0.001, n = 39 treatment comparisons, 1772 participants. Baseline blood pressure may play a role in the effect of cocoa on blood pressure. While systolic blood pressure was reduced significantly by 4 mmHg in hypertensive people (n = 9 treatment comparisons, 401 participants), and tended to be lowered in prehypertensive people (n= 8 treatment comparisons, 340 participants), there was no significant difference in normotensive people (n = 23 treatment comparisons, 1063 participants); however, the test for subgroup differences was of borderline significance (P = 0.08; I2 = 60%), requiring further research to confirm the findings. Subgroup meta-analysis by blinding suggested a trend towards greater blood pressure reduction in unblinded trials compared to double-blinded trials, albeit statistically not significant. Further research is needed to confirm whether participant expectation may influence blood pressure results. Subgroup analysis by type of control (flavanol-free versus low-flavanol control) did not reveal a significant difference. Whether the age of participants plays a role in the effect of cocoa on blood pressure, with younger participants responding with greater blood pressure reduction, needs to be further investigated. Sensitivity analysis excluding trials with authors employed by trials sponsoring industry (33 trials, 1482 participants) revealed a small reduction in effect size, indicating some reporting bias. Due to the remaining heterogeneity, which we could not explain in terms of blinding, flavanol content of the control groups, age of participants, or study duration, we downgraded the quality of the evidence from high to moderate. Results of subgroup analyses should be interpreted with caution and need to be confirmed or refuted in trials using direct randomised comparisons. Generally, cocoa products were highly tolerable, with adverse effects including gastrointestinal complaints and nausea being reported by 1% of participants in the active cocoa intervention group and 0.4% of participants in the control groups (moderate-quality evidence). Authors' conclusions: This review provides moderate-quality evidence that flavanol-rich chocolate and cocoa products cause a small (2 mmHg) blood pressure-lowering effect in mainly healthy adults in the short term. These findings are limited by the heterogeneity between trials, which could not be explained by prespecified subgroup analyses, including blinding, flavanol content of the control groups, age of participants, or study duration. However, baseline blood pressure may play a role in the effect of cocoa on blood pressure; subgroup analysis of trials with (pre)hypertensive participants revealed a greater blood pressure-reducing effect of cocoa compared to normotensive participants with borderline significance. Long-term trials investigating the effect of cocoa on clinical outcomes are also needed to assess whether cocoa has an effect on cardiovascular events and to assess potential adverse effects associated with chronic ingestion of cocoa products. © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.


MacPherson H.,Swinburne University of Technology | Ellis K.A.,University of Melbourne | Sali A.,National Institute of Integrative Medicine | Pipingas A.,Swinburne University of Technology
Psychopharmacology | Year: 2012

Rationale There is potential for multivitamin supplementation to improve cognition in the elderly. This randomized, double-blind, placebo-controlled trial was conducted to investigate the effects of 16 weeks multivitamin supplementation (Swisse Women's 50+ Ultivite ®) on cognition in elderly women. Methods Participants in this study were 56 community dwelling, elderly women, with subjective complaints of memory loss. Cognition was assessed using a computerized battery of memory and attention tasks designed to be sensitive to age-related declines to fluid intelligence, and a measure of verbal recall. Biochemical measures of selected nutrients, homocysteine, markers of inflammation, oxida-tive stress, and blood safety parameters were also collected. All cognitive and haematological parameters were assessed at baseline and 16 weeks post-treatment. Results The multivitamin improved speed of response on a measure of spatial working memory, however benefits to other cognitive processes were not observed. Multivitamin supplementation decreased levels of homocysteine and increased levels of vitamin B 6 and B 12, with a trend for vitamin E to increase. There were no hepatotoxic effects of the multivitamin formula indicating this supplement was safe for everyday usage in the elderly. Conclusion Sixteen weeks ssupplementation with a combined multivitamin, mineral and herbal formula may benefit working memory in elderly women at risk of cognitive decline. © 2011 Springer-Verlag.


Ried K.,University of Adelaide | Ried K.,National Institute of Integrative Medicine | Alfred A.,University of Adelaide
BMC Women's Health | Year: 2013

Background: Infertility affects about 15% of couples in Western-societies with most progressing to fertility clinics for treatment. Despite being common, infertility is often experienced as a lonely road for affected couples. In this paper we expand on our previously published findings of women's experiences with infertility or difficulty of viable pregnancy who had sought Traditional Chinese Medicine (TCM) therapy in Australia, and focus on women's quality of life, coping strategies, and support needs.Methods: We applied mixed methods using the Tuebingen Quality of Life and the COPE questionnaires and in-depth interviews with 25 women with primary or secondary infertility, recurrent miscarriages or unexplained stillbirth, and who had consulted a TCM practitioner. We used a thematic approach to analyse the interviews, and descriptive statistics to evaluate questionnaire responses.Results: Women reported through both questionnaires and interviews compromised quality of life due to the high level of distress, guilt, grief, and frustration caused by infertility. However, our women represented a highly motivated sample, actively seeking alternative support. While the TCM approach to infertility management increased women's sense of personal agency and control through education and continuity of care, the need for greater understanding and support on a societal level remains.Conclusions: In infertility, ongoing emotional and instrumental support is pivotal to the wellbeing and quality of life of the affected. Traditional Chinese Medicine addresses some support needs in infertility not routinely available in the Western model of care. More peer-led and professional-led support groups are greatly needed for women experiencing infertility to help break isolation and raise awareness of integrative approaches to fertility management. © 2013 Ried and Alfred; licensee BioMed Central Ltd.


Ried K.,University of Adelaide | Ried K.,National Institute of Integrative Medicine | Toben C.,University of Adelaide | Fakler P.,University of Adelaide
Nutrition Reviews | Year: 2013

Hypercholesterolemia is associated with an increased risk of heart disease. The effect of garlic on blood lipids has been studied in numerous trials and summarized in meta-analyses, with conflicting results. This meta-analysis, the most comprehensive to date, includes 39 primary trials of the effect of garlic preparations on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. The findings suggest garlic to be effective in reducing total serum cholesterol by 17±6mg/dL and low-density lipoprotein cholesterol by 9±6mg/dL in individuals with elevated total cholesterol levels (>200mg/dL), provided garlic is used for longer than 2 months. An 8% reduction in total serum cholesterol is of clinical relevance and is associated with a 38% reduction in risk of coronary events at 50 years of age. High-density lipoprotein cholesterol levels improved only slightly, and triglycerides were not influenced significantly. Garlic preparations were highly tolerable in all trials and were associated with minimal side effects. They might be considered as an alternative option with a higher safety profile than conventional cholesterol-lowering medications in patients with slightly elevated cholesterol. © 2013 International Life Sciences Institute.


Pase M.P.,Swinburne University of Technology | Grima N.,Monash University | Cockerell R.,Swinburne University of Technology | Stough C.,Swinburne University of Technology | And 3 more authors.
Journal of the American College of Nutrition | Year: 2015

Results: Treatment allocation had no effect on the primary cognitive outcomes at endpoint. Absolute increases in the red blood cell omega-3/6 ratio were associated with improvements in spatial working memory. The group receiving 6 g fish oil without the multivitamin displayed a significant decrease in aortic pulse pressure and aortic augmentation pressure, two measures of aortic blood pressure and aortic stiffness.Conclusions: Fish oil decreased aortic pulse pressure and augmentation pressure. Reductions in aortic blood pressure were not accompanied by consistent improvements in cognition.Objective: Fish oils and multivitamins are two of the most commonly used dietary supplements. Fish oil use may reduce vascular risk factors associated with cognitive decline, thus providing benefits to both heart and brain health. Multivitamins may also have direct effects on brain function. The present study investigated the effects of fish oil, with and without the addition of a multivitamin, on cognitive and cardiovascular function.Methods: In a randomized, placebo-controlled, double-blind fashion, 160 healthy adults aged 50–70 years were randomized to receive either 3 g of fish oil (240 mg eicosapentaenoic acid [EPA] + 240 mg docosahexaenoic acid [DHA]) with a multivitamin, 6 g of fish oil (480 mg EPA + 480 mg DHA) with a multivitamin, or 6 g of fish oil without a multivitamin or a placebo. Cognitive performance, brachial blood pressure, and aortic (central) blood pressure were measured at baseline, 6 weeks, and 16 weeks. © 2015, © American College of Nutrition.


Ried K.,University of Adelaide | Ried K.,National Institute of Integrative Medicine | Frank O.R.,University of Adelaide | Stocks N.P.,University of Adelaide
European Journal of Clinical Nutrition | Year: 2013

Background/objectives: Hypertension affects about 30% of adults worldwide. Garlic has blood pressure-lowering properties and the mechanism of action is biologically plausible. Our trial assessed the effect, dose-response, tolerability and acceptability of different doses of aged garlic extract as an adjunct treatment to existing antihypertensive medication in patients with uncontrolled hypertension. Subjects/methods: A total of 79 general practice patients with uncontrolled systolic hypertension participated in a double-blind randomised placebo-controlled dose-response trial of 12 weeks. Participants were allocated to one of three garlic groups with either of one, two or four capsules daily of aged garlic extract (240/480/960 mg containing 0.6/1.2/2.4 mg of S-allylcysteine) or placebo. Blood pressure was assessed at 4, 8 and 12 weeks and compared with baseline using a mixed-model approach. Tolerability was monitored throughout the trial and acceptability was assessed at 12 weeks by questionnaire. Results: Mean systolic blood pressure was significantly reduced by 11.8±5.4 mm Hg in the garlic-2-capsule group over 12 weeks compared with placebo (P=0.006), and reached borderline significant reduction in the garlic-4-capsule group at 8 weeks (-7.4±4.1 mm Hg, P=0.07). Changes in systolic blood pressure in the garlic-1-capsule group and diastolic blood pressure were not significantly different to placebo. Tolerability, compliance and acceptability were high in all garlic groups (93%) and highest in the groups taking one or two capsules daily. Conclusions: Our trial suggests aged garlic extract to be an effective and tolerable treatment in uncontrolled hypertension, and may be considered as a safe adjunct treatment to conventional antihypertensive therapy. © 2013 Macmillan Publishers Limited.


Rohner A.,University of Basel | Ried K.,National Institute of Integrative Medicine | Sobenin I.A.,Russian Cardiology Research and Production Complex | Bucher H.C.,University of Basel | Nordmann A.J.,University of Basel
American journal of hypertension | Year: 2015

BACKGROUND: Many patients prefer herbal medications to conventional drugs. Limited trial evidence suggests that garlic preparations reduce high blood pressure (BP).METHODS: We searched electronic databases through March 2014 to identify all randomized controlled trials that compared a garlic preparation to placebo in hypertensive patients. Trials were required to report BP values at baseline and after a follow-up of at least 4 weeks.RESULTS: Nine double-blind trials with 482 individuals fulfilled our inclusion criteria. Included trials were rather small, and the quality of the majority of included trials was moderate. Follow-up ranged from 8 to 26 weeks. All trials reported office BP measurements. Systolic BP and diastolic BP (SBP and DBP) were more effectively reduced in individuals treated with garlic preparations than in individuals treated with placebo. However, heterogeneity was high (weighted mean difference (WMD) for SBP was -9.1 mm Hg; 95% confidence interval (CI), -12.7 to -5.4; P for heterogeneity = 0.0006; and I2 = 71%; WMD for BP was -3.8 mm Hg; 95% CI, -6.7 to -1.0; P for heterogeneity = 0.00001; I2 = 80%). When analyses were restricted to higher-quality trials using intention-to-treat analysis or to trials with concealed treatment allocation and standardized and blinded BP measurement, effect sizes for SBP but not for DBP were lower and heterogeneity disappeared.CONCLUSIONS: Although evidence from this review suggests that garlic preparations may lower BP in hypertensive individuals, the evidence is not strong. A well-conducted and powered trial of longer duration is needed to confirm these findings. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.


Ried K.,National Institute of Integrative Medicine
Complementary Therapies in Medicine | Year: 2015

Objectives: To assess the effect of Traditional Chinese herbal medicine (CHM) in the management of female infertility and on pregnancy rates compared with Western medical (WM) treatment and update previous meta-analyses. Methods: We searched the Medline and Cochrane databases until December 2013 for randomized controlled trials and meta-analyses investigating Chinese herbal medicine therapy for female infertility and compared clinical pregnancy rates achieved with CHM versus WM drug treatment. Results: Forty RCTs involving 4247 women with infertility were included in our systematic review. Meta-analysis suggested a 1.74 higher probability of achieving a pregnancy with CHM therapy than with WM therapy alone (risk ratio 1.74, 95%CI: 1.56-1.94; p<. 0.0001; odds ratio 3.14; 95%CI: 2.72-3.62; p<. 0.0001) in women with infertility. Trials included women with PCOS, endometriosis, anovulation, fallopian tube blockage, or unexplained infertility. Mean pregnancy rates in the CHM group were 60% compared with 33% in the WM group. Conclusions: Our review suggests that management of female infertility with Chinese herbal medicine can improve pregnancy rates 2-fold within a 3-6 month period compared with Western medical fertility drug therapy. In addition, fertility indicators such as ovulation rates, cervical mucus score, biphasic basal body temperature, and appropriate thickness of the endometrial lining were positively influenced by CHM therapy, indicating an ameliorating physiological effect conducive for a viable pregnancy. © 2015 Elsevier Ltd.


Background: Garlic has been shown to have cardiovascular protective and immunomodulatory properties. Objectives: We updated a previous meta-analysis on the effect of garlic on blood pressure and reviewed the effect of garlic on cholesterol and immunity. Methods: We searched the Medline database for randomized controlled trials (RCTs) published between 1955 and December 2013 on the effect of garlic preparations on blood pressure. In addition, we reviewed the effect of garlic on cholesterol and immunity. Results: Our updated meta-analysis on the effect of garlic on blood pressure, which included 20 trials with 970 participants, showed a mean6SE decrease in systolic blood pressure (SBP) of 5.162.2mmHg (P < 0.001) and a mean6 SE decrease in diastolic blood pressure (DBP) of 2.5 6 1.6 mm Hg (P < 0.002) compared with placebo. Subgroup analysis of trials in hypertensive subjects (SBP/DBP ≥140/90 mm Hg) at baseline revealed a larger significant reduction in SBP of 8.7 6 2.2 mm Hg (P < 0.001; n = 10) and in DBP of 6.1 6 1.3 mm Hg (P < 0.001; n = 6). A previously published meta analysis on the effect of garlic on blood lipids, which included 39 primary RCTs and 2300 adults treated for aminimumof 2wk, suggested garlic to be effective in reducing total and LDL cholesterol by 10% if taken for > 2 mo by individuals with slightly elevated concentrations [e.g., total cholesterol > 200mg/dL (> 5.5 mmol/L)]. Garlic has immunomodulating effects by increasing macrophage activity, natural killer cells, and the production of T and B cells. Clinical trials have shown garlic to significantly reduce the number, duration, and severity of upper respiratory infections. Conclusions: Our review suggests that garlic supplements have the potential to lower blood pressure in hypertensive individuals, to regulate slightly elevated cholesterol concentrations, and to stimulate the immune system. Garlic supplements are highly tolerated and may be considered as a complementary treatment option for hypertension, slightly elevated cholesterol, and stimulation of immunity. Future long-term trials are needed to elucidate the effect of garlic on cardiovascular morbidity and mortality. © 2016 American Society for Nutrition.


Ried K.,National Institute of Integrative Medicine | Fakler P.,National Institute of Integrative Medicine
Integrated Blood Pressure Control | Year: 2014

Garlic supplements have shown promise in the treatment of uncontrolled hypertension, lowering blood pressure (BP) by about 10 mmHg systolic and 8 mmHg diastolic, similar to standard BP medication. Aged garlic extract, which contains S-allylcysteine as the bioactive sulfur compound, in particular is standardizable and highly tolerable, with little or no known harmful interaction when taken with other BP-reducing or blood-thinning medication. Here we describe biologically plausible mechanisms of garlic’s BP-lowering effect. Garlic-derived polysulfides stimulate the production of the vascular gasotransmitter hydrogen sulfide (H2S) and enhance the regulation of endothelial nitric oxide (NO), which induce smooth muscle cell relaxation, vasodilation, and BP reduction. Several dietary and genetic factors influence the efficiency of the H2S and NO signaling pathways and may contribute to the development of hypertension. Sulfur deficiency might play a part in the etiology of hypertension, and could be alleviated with supplementation of organosulfur compounds derived from garlic. © 2014 Ried and Fakler.

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