Fitoterapia 85 (2013) 84–94

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Fitoterapia

j ourna l homepage: www.e lsev ie r .com/ locate / f i to te

Review

Hibiscus sabdariffa L. in the treatment of hypertension andhyperlipidemia: A comprehensive review of animal andhuman studies

Allison L. Hopkins a,⁎, Marnie G. Lamm a, Janet L. Funk b, Cheryl Ritenbaugh a

a Department of Family and Community Medicine, University of Arizona, Tucson, AZ 85724, USAb Department of Medicine, University of Arizona, Tucson, AZ 85724, USA

a r t i c l e i n f o

⁎ Corresponding author. Tel.: +1 520 488 3751.E-mail address: hopkin28@email.arizona.edu (A.L.

0367-326X/$ – see front matter. Published by Elseviehttp://dx.doi.org/10.1016/j.fitote.2013.01.003

a b s t r a c t

Article history:Received 3 February 2012Accepted in revised form 3 January 2013Available online 17 January 2013

The effectiveness of Hibiscus sabdariffa L. (HS) in the treatment of risk factors associated withcardiovascular disease is assessed in this review by taking a comprehensive approach tointerpreting the randomized clinical trial (RCT) results in the context of the availableethnomedical, phytochemical, pharmacological, and safety and toxicity information. HSdecoctions and infusions of calyxes, and on occasion leaves, are used in at least 10 countriesworldwide in the treatment of hypertension and hyperlipidemia with no reported adverseevents or side effects. HS extracts have a low degree of toxicity with a LD50 ranging from 2,000to over 5,000 mg/kg/day. There is no evidence of hepatic or renal toxicity as the result of HSextract consumption, except for possible adverse hepatic effects at high doses. There isevidence that HS acts as a diuretic, however in most cases the extract did not significantlyinfluence electrolyte levels. Animal studies have consistently shown that consumption of HSextract reduces blood pressure in a dose dependent manner. In RCTs, the daily consumption ofa tea or extract produced from HS calyxes significantly lowered systolic blood pressure (SBP)and diastolic blood pressure (DBP) in adults with pre to moderate essential hypertension andtype 2 diabetes. In addition, HS tea was as effective at lowering blood pressure as thecommonly used blood pressure medication Captropril, but less effective than Lisinopril. Totalcholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides were lowered inthe majority of normolipidemic, hyperlipidemic, and diabetic animal models, whereashigh-density lipoprotein cholesterol (HDL-C) was generally not affected by the consumptionof HS extract. Over half of the RCTs showed that daily consumption of HS tea or extracts hadfavorable influence on lipid profiles including reduced total cholesterol, LDL-C, triglycerides, aswell as increased HDL-C. Anthocyanins found in abundance in HS calyxes are generallyconsidered the phytochemicals responsible for the antihypertensive and hypocholesterolemiceffects, however evidence has also been provided for the role of polyphenols and hibiscus acid.A number of potential mechanisms have been proposed to explain the hypotensive andanticholesterol effects, but the most common explanation is the antioxidant effects of theanthocyanins inhibition of LDL-C oxidation, which impedes atherosclerosis, an importantcardiovascular risk factor. This comprehensive body of evidence suggests that extracts of HSare promising as a treatment of hypertension and hyperlipidemia, however more high qualityanimal and human studies informed by actual therapeutic practices are needed to providerecommendations for use that have the potential for widespread public health benefit.

Published by Elsevier B.V.

Keywords:Hibiscus sabdariffa L.RoselleHypertensionCholesterolRandomized clinical trialsEthnopharmacology

Hopkins).

r B.V.

85A.L. Hopkins et al. / Fitoterapia 85 (2013) 84–94

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 852. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

2.1. Information sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 852.2. Search . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 852.3. Data collection process and data items . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86

3. Ethnomedicinal uses and preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 864. Phytochemical properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 865. Safety and toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 866. HS in the treatment of high blood pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

6.1. Animal studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 876.2. Human study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

7. HS in the treatment of elevated cholesterol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 887.1. Animal studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 887.2. Human studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89

8. Quality of RCT reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 899. Biological mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92

10. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92

1. Introduction1

Hibiscus sabdariffa L. (HS) (Malvaceae) tea is in wide-spread use across the world as a beverage and as a treatmentfor hypertension and hyperlipidemia. Two systematic reviewshave been published on the effectiveness of HS for thetreatment of hypertension [1,2]. However Ngamjarus andcolleagues [2] excluded all randomized clinical trials (RCTs) asbeing of too low quality, and Wahabi and colleagues [1]established the quality of studies using the Jadad scale, a scalewhich focuses exclusively on randomization, blinding andparticipant withdrawals [3–6]. Both reviews determined thatthe evidence available at the time of reviewwas inconclusive.

However, subsequent to the publication of these twoprevious reviews, expanded criteria allowing for a morecomprehensive evaluation of the totality of evidence relatedto the medicinal use of botanicals have been proposed byFonnebo and colleagues [7]. This review applies theseupdated and expanded criteria to assess data related to theuse of HS for hypertension, including data from a high qualitystudy published subsequent to earlier reviews [8]. Further-more, to obtain a more complete view of potential protectiveeffects of HS as relates to cardiovascular disease, evidencerelated to HS effects on cholesterol metabolism are alsoreviewed. These data are reviewed in the context ofethnomedicinal information on HS use, preparation, anddosage and updated phytochemical, pharmacological, and

1 RCT, randomized clinical trial; HS,H. sabdariffa,Hibiscus sabdariffa L.; AST,aspartate aminotransferase; ALT, alanine aminotrasferase; HCTZ,hydrocholorthiazide; GAE, gallic acid equivalents; CGE, cyanidin glucosideequivalents; ORAC, oxygen radical absorbance capacity; ACE, angiotensin Iconverting enzyme; PI3-K, phosphoinositol 3-kinase; LDL, low-densitylipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; CTGF,connective tissue growth factor; RAGE, receptor of advanced glycation endproduct; HMG-CoA, 3-hydroxy-3-methylglutaryl-coenzyme A; LD50, medianlethal dose; CONSORT, Consolidated Standards of Reporting Trials; SBP,systolic blood pressure; DBP, diastolic blood pressure.

toxicological information on HS, which was last reviewed byAli and colleagues in 2005 [9].

The objective of this review is to:

• Examine the evidence of the effectiveness of HS oncardiovascular risk factors based on ethnomedicinal, safetyand toxicity, pharmacological, phytochemical information

2. Methods

2.1. Information sources

The following databases were searched from commence-ment to November 14, 2012: AGRICOLA, AMED, BIOSISPreviews, Cochrane Library, International PharmaceuticalAbstracts, ISI Web of Knowledge, MEDLINE, Pubmed, NaturalMedicines Comprehensive Database. We also used otherresources, such as Clinical Trials.gov and Current ControlledTrials, WorldWideScience.org, OpenGrey, hand searching ofjournals and reference lists of all papers and relevant reviewsidentified, to find any additional studies that were notcaptured in the databases. Additionally, original articles wereretrieved from existing reviews [1,2,9] and re-reviewed.

2.2. Search

We used the search terms of Hibiscus or Hibiscus sabdariffaand hypertension or cholesterol. Using the additional searchterms of the commonnames for HS, including Sour Tea, Roselle,Red Sorrel, Karkade, Jamaica, or Flor de Jamaica, or herbal tea orherbal medicine in combination with high blood pressure,elevated blood pressure, hypertension, pre-hypertension, mildhypertension, or dyslipidemia, hypercholesterolemia, lipidprofiles, hypolipidemic effect, hyperlipidemic, or atherosclerosisdid not yield any further results.

The literature search using keywords “hypertension” and“hibiscus” resulted in the retrieval of 154 titles, 70 of whichwere duplicates and 28 were regarding species or conditions

86 A.L. Hopkins et al. / Fitoterapia 85 (2013) 84–94

not focused on in this review. After removing irrelevantarticles, 77 articles remained for review, of which 5 were RCTs[8,10–13]. In the second literature search “hibiscus” was keptas a keyword and “hypertension” was replaced with “choles-terol”. The search yielded 167 total titles, of which 58duplicates and 30 articles were removed because they focusedon irrelevant species or conditions. The remaining 79 articleswere reviewed, 5 of which were RCTs [14–18].

2.3. Data collection process and data items

The articles identified using the aforementioned searchstrategy were sorted into the following categories: ethnobot-any, safety and toxicity, pharmacology,with animal and humanstudies in separate categories, and phytochemistry. The datafrom the RCT studies were extracted and categorized by twoauthors (AH and ML) and presented in appropriate sections.The quality of trial and herbal intervention reporting in theRCTs was assessed by the same authors through determiningthe percentage of items reported from herbal interventionselaboration of the 2001 Consolidated Standards of ReportingTrials (CONSORT) statement, as these reflect the industrystandard for theminimum information necessary for reportingRCTs at the time most of the trials in this review were carriedout [4,19,20].

3. Ethnomedicinal uses and preparation

HS is consumed as a beverage in theUnited States [8],Mexico[11,13,16], Nigeria and other West African countries [21–25],Egypt [26], Iran [10,14,18], India [17,27,28], Thailand [29], andTawian [15,30,31], among other countries. Ethnomedicinalstudies have reported the use of HS for the treatment of variouscardiovascular risk factors including hypertension in Egypt,Jordan, and Trinidad and Tobago [32–35], hypotension in Jordanand Iraq [34,36], hyperlipidemia in Jordan, Greece, Brazil, andTrinidad and Tobago [33,35,37,38], and obesity in Iraq, Greece,and Brazil [36–38].

The flowers, or more specifically the calyxes, are typicallyprepared using an aqueous decoction or infusion [32,33,36,38].However, the Bedouins in the North Badia region of Jordan usethe leaves, as well as the flowers, and they drink the infusionshot when treating high blood pressure and cold when treatinglowblood pressure [34]. In Trinidad and Tobago only the leavesare used to treat high blood pressure and the flower and seedsare used to treat high cholesterol [35]. Dosing was onlydescribed in 1 [36] of the 7 ethnobotancial studies reviewed.Mati and colleagues [36] discovered that herbalists in theKurdistan Autonomous Region of Iraq recommend drinking 1cup/day of an infusion of 1 tsp (1/2 tsp when ground) of HSflowers in 1 cup warm water for the treatment of hypotensionand 2 cups/day of a decoction of 2 tsp of the HS flowers in 1/2 Lof water or 1 cup/day of a decoction of 50 g in 2 cups of waterfor the treatment of obesity.

4. Phytochemical properties

The main compounds found in HS flowers are organicacids, mainly citric and malic acids, anthocyanins, a myriad offlavonoids and glycosides, and fiber [9,39–41]. The calyxeshave the same organic acid and anthocyanin constituents, but

the presence of flavonoids and glycosides is minimal [9].Anthocyanins, particularly delphinidin-3-sambubioside andcyanidin-3-sambubioside, are generally believed to be theactive constituents responsible for the anti-hypertensive,antioxidant, and hypocholesterolemic effects of HS, possiblybecause they are found in high relative quantities in aqueousextracts [8,11,13,16]. However, Yang [42] compared apolyphenol rich (74%) extract containing protocatechuic acid(24.2%), catechin (2.7%), gallocatechins (2.4%), caffeic acid(19.9%), and gallocatechin gallates (30.0%) with an aqueousextract of HS containing anthocyanins (2.5%), polyphenolic acid(1.7%) and flavonoids (1.4%) and determined that the phenolrich extract exhibited a greater ability to decrease totalcholesterol and LDL-C cholesterol and increased HDL-C choles-terol dose-dependently suggesting the importance of poly-phenols in inducing anti-cholesterol effects. Hibiscus acid mayalso be playing a role in lower blood pressure and cholesterol[43].

The plant parts used, the color of the parts, the harvestingpractices and the preparation method greatly influence thevolatile composition of the extract and influence dosing [9].The HS varieties with deeper red calyxes exhibited greaterantioxidant activity as compared to lighter red orwhite varieties[44,45]. Greater antioxidant activity was found in flowers thatwere harvested at 35 days after flowering as compared to lessmature flowers [45]. Ethanol extractions of calyxes exhibited thehighest antioxidant activity as compared to ethanol extractionsof leaves and aqueous extractions of both plant parts [28].However, aqueous extractions are appropriate for studiesinterested in testing the effectiveness of traditional preparationpractices and capturing the broad public health implications ofthis herbal treatment.

Very little research has been done on the bioavailability ofHS extract. McKay and colleagues [8] provide the onlyexception in their clinical trial where they brewed HS teaby steeping 1250 mg of dried HS in 240 mL of boiled water,administering one such serving 3 times a day. No anthocy-anins were detected in the urine within one hour ofconsumption of this HS tea, which contained 22 mg gallicacid equivalents (GAE) total phenols, 7 mg cyanidin glucosideequivalents (CGE) total anthocyanins, 4 mg CGE delphinidin-3-sambubioside, 0.02 mg CGE cyanidin-3-sambubioside, and1950 μmol trolox equivalents/g oxygen radical absorbancecapacity (ORAC).

5. Safety and toxicity

Studies carried out in animals and humans have primarilydemonstrated either no change or decreases in measuresrelated to function of the liver (AST and ALT liver enzymes[16,46,47]) or kidney (creatinine [16,18,22,23,31,46,48], bloodurea nitrogen [18,31], and urea [16]) function (Table 1).However, at doses of 300 mg/kg/day of HS over a 3 monthperiod, an adverse effect on liver enzymes was observed,suggesting that at very high doses the extract could behepatotoxic [46]. Uric acid levels were reported to be elevatedin rodents given extremely high doses of HS, a potentialadverse effect that could exacerbate or contribute to thedevelopment of gout [23].

HS extracts administered at 500 mg/kg/day over the courseof 3 weeks exhibited diuretic properties in hypertensive

Table 1Effect of administration of HS extracts on creatinine, urea, AST, ALT, and electrolyte levels in rodents and humans.

Primary author, year, type of study Plant Part Extract mode Dose End time point Crea Urea AST ALT Mg Na K Cl

Fakeye, 2008, * C A, A; W/A 50a, 100a; 100a 7 NSLee, 2009, * F A 100a 60 NS DepLee, 2009, * F A 200a 60 NS DepFakeye, 2009, * C W/A 300a 90 N/A N/A N/AFakeye, 2009, * C A 300a 90 NS NS EleOnyenekwe, 1999, * P W 500a 60 Dep EleOnyenekwe, 1999, * P W 500a 60 Dep EleOnyenekwe, 1999, * P W 1000a 60 Dep EleKuo, 2012, * F W 1b 35 NS NS NS NSKuo, 2012, * F W 2b 35 NS Dep NS NSKuo, 2012, * F W 5b 35 NS Dep NS NSGurrola-Diaz, 2010, ** C A 100c 30 NS NS Red RedGurrola-Diaz, 2010, ** C A 100c 30 NS NS NS NSMohagheghi, 2011, ** C W 30/4d 30 NS NS NS NSNdu, 2011, * C A 40a 1 NS NS NSOdigie, 2003, * P W 250a 60 NS NS NS NS NSHerrera-Arellano, 2004, ** C W 9.62e 30 Inc NS NSHerrera-Arellano, 2007, ** C W 250e 30 NS NS Inc

Notes: Type of study: *=animal studies with rats or mice, **=human studies; Plant part used in extract=F=flower, C=calyx, P=petal; Extract mode: W=water, A=alcohol; Dose: a=mg of HS extract/kg weight of animal/day, b=%, c=mg of HS extract/day, d=mg HS plant part/glasses of water/day, e=mganthocyanins/day; End time point: number of days after start of treatment when measurement was taken; Crea=creatinine; Urea: some measurements in thiscolumn are Uric acid or Blood Urea Nitrogen; AST=aspartate aminotransferase; ALT=alanine aminotransferase; Mg=Magnesium; Na=Sodium; K=Potassium; Cl=Chlorine; Results: N/A=not available, NS=not significant, Dep=depressed, Ele=elevated, Red=reduced, Inc=increased, depressed orelevated used when values compared with appropriate control, increased or reduced used when values compared between baseline and end of treatment withinthe same group.

87A.L. Hopkins et al. / Fitoterapia 85 (2013) 84–94

animal models. HS consumption in most cases had nosignificant effect on electrolytes, includingmagnesium, sodium,potassium, and/or chlorine/chloride [11,13,18,22,49], althoughsodium [13] and chlorine levels [11] in humans increasedstatistically significantly from baseline to final measurement at30 days of receiving HS extract. The diuretic behavior ofHS extract in these two studies has been compared to thepotassium sparing group of diuretic pharmaceuticals, such asSpironolactone or aldosterone antagonists [11,13].

A few other studies among animals suggest that HSextracts have a low degree of acute toxicity with the medianlethal dose (LD50) ranging from 2000 to over 5000 mg/kg[23,46,49]. In contrast, one studied showed that doses as highas 4600 mg/kg can be administered for several months in ananimal model with no report of mortality, although negativeeffects on testes and sperm count were found [50]. Thevariation in these findings may be due to the type of solventsused for extraction, the method and length of administrationand the variety of HS used [46].

Herb-drug interactions between HS and hydrochlorothiazide(HCTZ) [49], a commonly prescribed diuretic medication, andacetaminophen [51], an antipyretic-analgesic over-the-countermedication, were examined. Co-administration of HS extract(40 mg/kg) and HCTZ (10 mg/kg) in rats caused a significantincrease in the volume of urine excreted, but electrolytelevels were more similar to controls than HCTZ alone [49].Pharmacokinetics measurements in rabbits suggest that co-administration of HS (20–40 mg/kg) and HCTZ (10 mg/kg)may result in retention of HCTZ, less clearing of HCTZ fromthe body with increased doses of HS, and slower HCTZelimination. These results suggest a possible herb-druginteraction and HS should not be used in conjunction withHCTZ. The only pharmacokinetic effect of consumption of HSin adult males before taking acetaminophen was enhanced

elimination of the acetaminophen [51]. Based on thesefindings, acetaminophen should be taken 3–4 hours beforedrinking HS to avoid shortening its therapeutic effect.

6. HS in the treatment of high blood pressure

6.1. Animal studies

The results from animal studies presented in Table 2consistently show the beneficial effects of HS extracts onlowering blood pressure [21–23,52]. Although the same effectson blood pressure occur in normotensive animal models, thepositive effects are greater in hypertensive animals [21,23].Aqueous extracts of HS calyxes and petals at doses rangingfrom 1 mg/kg/day through 1000 mg/kg/day were effective inreducing blood pressure among rodent models [21–23,52](Table 2). There is evidence that the positive effects are dosedependent at lower doses [21], but not at extremely high doses[23].

6.2. Human study

The clinical study populations ranged from pre and mildlyhypertensive [8,10] to stage 1 or 2 hypertensive [11,12](Table 3; Table 6 quality of reporting). Only one study choseto recruit people with the additional condition of type 2diabetes [10]. The study designs included comparing HS toblack tea [10], blood pressure medication [11,13], or a placebobeverage [8]. HS was generally prepared as a tea, but Herrera-Arellano and colleagues [11] prepared it as a standardizedaqueous extract. Dried calyxes of HS were used in the tea orextract in those studies (4 of 5) that specifiedwhich part of theplant was use [8,11,13]. The amount of HS plant part extractedper serving varied from 1.25 g to 10 g with lower doses being

Table 2Effect of administration of HS extract on rodent systolic and diastolic blood pressure.

Primary author,year

Condition Samplesize

PlantPart

Extractmode

Dose End timepoint

Within groupSBP

Between groupSBP

Within groupDBP

Between groupDBP

Mojiminiyi, 2007 Normo 6 rats C W 1a 1 Red RedMojiminiyi, 2007 Normo 6 rats C W 5a 1 Red RedMojiminiyi, 2007 Normo 6 rats C W 25a 1 Red RedMojiminiyi, 2007 Normo 6 rats C W 125a 1 Red RedOnyenekwe, 1999 Normo 5 rats P W 500a 21 Red N/A Red N/AOnyenekwe, 1999 Normo 5 rats P W 1000a 21 Red N/A Red N/AMojiminiyi, 2007 Hypera 6 rats C W 1a 1 NS NSMojiminiyi, 2007 Hyperb 6 rats C W 1a 1 Red RedMojiminiyi, 2007 Hypera 6 rats C W 5a 1 Red RedMojiminiyi, 2007 Hyperb 6 rats C W 5a 1 Red RedMojiminiyi, 2007 Hypera 6 rats C W 25a 1 Red RedMojiminiyi, 2007 Hyperb 6 rats C W 25a 1 Red RedMojiminiyi, 2007 Hypera 6 rats C W 125a 1 Red RedMojiminiyi, 2007 Hyperb 6 rats C W 125a 1 Red RedOdigie, 2003 Hyper 5 rats P W 250a 56 Red Dep N/A DepOnyenekwe, 1999 Hyper 5 mice P W 500a 21 Red Dep Red DepOnyenekwe, 1999 Hyper 5 mice P W 1000a 21 N/A N/A N/A N/AInuwa, 2012 Hyper 8 rats C W 10b 70 Red Dep Red DepInuwa, 2012 Hyper 8 rats C W 15b 70 Red Dep Red DepInuwa, 2012 Hyper 8 rats C W 20b 70 Red Dep Red DepInuwa, 2012 Hyper 6 rats F A 50a 5 NS NSInuwa, 2012 Hyper 6 rats F A 100a 5 NS NSInuwa, 2012 Hyper 6 rats F A 200a 5 NS NS

Notes: Condition: Normo=normotension, Hyper=hypertension, a=salt loaded induced, b=chronic oxide synthase inhibition induced; Plant part used inextract=F=flower, C=calyx, P=petal; Extract mode: W=water, A=alcohol; Dose: a=mg of HS extract/kg weight of animal/day, b=%; End time point:number of days after start of treatment when measurement was taken; SBP=Systolic blood pressure; DBP=Diastolic blood pressure; Results: N/A=notavailable, NS=not significant, Dep=depressed, Ele=elevated, Red=reduced, Inc=increased, depressed or elevated used when values compared withappropriate control, increased or reduced used when values compared between baseline and end of treatment within the same group.

88 A.L. Hopkins et al. / Fitoterapia 85 (2013) 84–94

administered up to 3 times per day and higher doses beingadministered only once. The duration of most of the studieswas 4 weeks [10,11,13], although one study only lasted 12 days[12] and another was 6 weeks long [8].

Systolic blood pressure (SBP) and diastolic blood pressure(DBP) declined with HS treatment in all but one study whereDBP did not achieve statistical significance relative to pre-treatment levels [10]. When comparing the results of the HSexperimental groups with the placebo and black tea groups,the decline in SBP and DBP was significantly greater in the HSexperimental groups [8,10,12]. When comparing effects of HSto those of two commonly used ACE-inhibitors, HS was aseffective as Captopril in lowering SBP and DSP in one study[13], but less effective than Lisinopril in another [11].

7. HS in the treatment of elevated cholesterol

7.1. Animal studies

The data presented in Table 4 indicates that results fromstudies of the effect of HS extract on animal cholesterolmetabolism are varied. Total cholesterol was reduced amonghealthy rats administered 1.5 mg/kg/day red and green HSpetal aqueous extract and 200 mg/kg/day flower alcoholextract ingested over the course of a month, respectively[24,25], however 200 mg/kg/day calyx alcohol extract ad-ministered for over two months showed no effect [30].High-density lipoprotein cholesterol (HDL-C) was not statis-tically significantly impacted by HS extract consumption[24,25,30] and low-density lipoproteins (LDL-C) was reduced

at lower doses [24], but no data was available at higher doses[25,30]. Triglycerides were significantly reduced at a dose of200 mg/kg/day HS flower alcohol extract [25].

In hyperlipidemic animal models all of the aqueous calyxand flower extracts reduced total cholesterol regardless of doseor length of administration [29,53,54]. Alcohol calyx and leafextracts also reduced total cholesterol at doses between 200and 500 mg/kg/day [27,28,30]. The majority of the studiesindicated that HDL-C levels in hyperlipidemic animal modelswere unaffected by the consumption of the HS extract[27,29,43,53,54] but one study reported an increase in HDL-Cwith consumption of 500 mg/kg/day leaf or calyx alcoholextracts for a month [28]. LDL-C cholesterol was consistentlyreduced among aqueous and alcohol calyx extracts regardlessof dose and duration of administration [27–29,43,53,54].Alcohol leaf extracts only showed a positive effect at dosesbetween 200 and 500 mg/kg/day [27,28]. Triglycerides werereduced among lower doses of aqueous calyx extracts[26,29,53], but not with extremely high doses [29,54]. Alcoholcalyx extracts were effective at reducing triglycerides at alldoses and administration lengths and subjects receivingalcohol leaf extracts responded positively to doses between200 and 500 mg/kg/day.

In diabetic animal models 100 and 200 mg/kg/day ethanolextracts of HS calyxes administered over the course ofapproximately 2 months showed a reduction of total choles-terol, LDL-C and triglycerides [30,31]. An extract of HS flowersusing the samedoses and extractionmethod,with a duration ofadministration half the previously mentioned studies, onlyexhibited a reduction in total cholesterol in diabetic rats [25].

Table3

Hyp

ertens

ionRC

Tinterven

tion

san

deffectson

systolic

bloo

dpressu

rean

ddiastolic

bloo

dpressu

re.

Prim

aryau

thor,

year

Cond

ition

Sample

size

Subs

tanc

ePlan

tpa

rtEx

tract

mod

eDose

#of

doses

perda

yDay

sdo

setake

nMea

nch

ange

inSB

P(SD)

Withingrou

pp-va

lue

Betw

eengrou

pp-va

lue

Mea

nch

ange

inDBP

(SD)

Withingrou

pp-va

lues

Betw

eengrou

pp-va

lues

McK

ay,2

010

Hyp

er31

(30)

AHFC

W1.2/24

0a3

421.3(1

0.0)

NS

0.5(7

.5)

NS

McK

ay,2

010

Hyp

er35

(35)

HS

CW

2.25

/240

b3

427.2(1

1.4)

Red

Dep

3.1(7

.0)

Red

Dep

Haji,19

99Hyp

er40

(23)

BTL

W2/1c

112

6.3(7

.7)

Red

3.5(6

.0)

Red

Haji,19

99Hyp

er40

(31)

HS

N/A

W2/1c

112

17.6

(6.8)

Red

Dep

a10

.9(5

.4)

Red

Dep

a

Moz

affari-K

hosrav

i,20

09Hyp

er,D

iab

30(2

6)BT

LW

2/24

0b2

308.4(1

1.0)

Inc

4.6(1

1.8)

NS

Moz

affari-K

hosrav

i,20

09Hyp

er,D

iab

30(2

7)HS

CW

2/24

0b2

3015

.4(7

.5)

Red

Dep

4.3(1

2.3)

NS

Dep

Herrera-A

rella

no,2

004

Hyp

er37

(32)

Med

a25

d2

2816

.4(9

.6)

Red

13.1

(7.2)

Red

Herrera-A

rella

no,2

004

Hyp

er53

(38)

HS

CW

9.62

e1

2814

.2(1

1.8)

Red

NS

11.2

(6.9)

Red

NS

Herrera-A

rella

no,2

007

Hyp

er93

(N/A

)Med

b10

d1

2823

.3(7

.0)

Red

15.4

(6.0)

Red

Herrera-A

rella

no,2

007

Hyp

er10

0(N/A

)HS

CW

250e

128

17.1

(10.0)

Red

Dep

b12

.0(7

.0)

Red

Dep

b

Notes:Co

ndition:

Hyp

er=

hype

rten

sion

,Diab=

diab

etes;Sa

mplesize

:be

ginn

ingof

stud

y(end

ofstud

y),N

/A=

notav

ailable;

Subs

tanc

e:AHFC

=artific

ialh

ibiscu

sfla

vorco

ncen

trate,

HS=

Hibiscu

ssabd

ariffa,

BT=

Black

tea,Med

=bloo

dpressu

remed

ication,

a=

Captop

ril,

b=

Lisp

inop

ril;Plan

tpa

rtus

edin

extract:C=

calyx,

L=leaf;E

xtract

mod

e:W

=water;D

ose:

a=

mLsu

bstanc

e/mLex

traction

subs

tanc

e;b=

gsu

bstanc

e/mLex

traction

subs

tanc

e,c=

spoo

nfulsof

subs

tanc

e/glassof

extraction

subs

tanc

e,d=

mgof

subs

tanc

e,e=

mgtotala

ntho

cyan

ins;

SBP=

Systolic

bloo

dpressu

re,D

BP=

Diastolic

bloo

dpressu

re,S

D=

stan

dard

deviation;

Resu

lts:

NS=

not

sign

ificant,D

ep=

depressed,

a=

morethan

compa

rator,

b=

less

than

compa

rator,Ele=

elev

ated

,Red

=redu

ced,

Inc=

increa

sed,

depressedor

elev

ated

used

whe

nva

lues

compa

redwithap

prop

riateco

ntrol,increa

sedor

redu

cedus

edwhe

nva

lues

compa

redbe

twee

nba

selin

ean

den

dof

trea

tmen

twithinthesamegrou

p.

89A.L. Hopkins et al. / Fitoterapia 85 (2013) 84–94

HDL-C was not significantly changed by HS extract consump-tion in diabetic animals [25,31].

7.2. Human studies

The clinical study populations were diverse and includedhealthy people as well as those with metabolic syndrome[16], hyperlipidemia [15,17], hypertension [18], or type 2diabetes [14] (Table 5; Table 6 quality of reporting). The studydesigns compared different doses of HS [15] or compared HS toblack tea [14,18], diet and a combination of HS and diet [16], ora placebo [17]. In two studies the dried calyxes of HS wereprepared and administered as a tea [14,18] and in the otherstudies fresh calyxes [15,16] or leaves [17] were prepared as astandardized powdered extract and administered in capsules.The doses of HS per serving and the frequency of administra-tion varied from .015 g of dried calyxes prepared in water andadministered twice daily [18] to 450 g of dried calyxesprepared in water and administered up to 3 times a day [15].Alcohol extractions formulated with 500 g of fresh calyxeswere administered once daily [16] and alcohol extracts madefrom 60,000 g of fresh leaves were administered twice daily[17]. The duration of the studies ranged from 15 days [18] to90 days [17] with most lasting 1 month [14–16].

The effect of HS on total cholesterol varied. One brief 15 daystudy reported a significant increase in total cholesterol amonghypertensive patients administeredHS [18]. In this same study,HDL-C increased and triglyceride and LDL-C values remainedunchanged. Of the remaining 4 studies, one showed nosignificant change in total cholesterol and the month longstudies showed significant decreases in total cholesterol amongparticipants with hypertension,metabolic syndrome and thosereceiving the two lower doses of HS [14–16]. HS significantlyincreased beneficial HDL-C levels in participants with andwithout metabolic syndrome [16] and hypertension [14]. LDL-C was significantly decreased as a result of the consumption ofHS in participants with metabolic syndrome [16], hyperlipid-emia [17], and type 2 diabetes [14]. Triglyceride levels weresignificantly decreased by HS in participants with hyperlipid-emia [17], type 2 diabetes [14], andwithoutmetabolic syndrome[16].

8. Quality of RCT reporting

The studies consistently reported the CONSORT itemsrelevant to all RCTs with scores ranging from 59% [15] of theitems reported to 96% [8] (Table 6). The items 1–6 and 12werereported by most RCTs and included information on eligibilitycriteria for participants, a description of the intervention,outcome measurements and statistical methods (item 12).Items from the results section including participant flow (item13), baseline data (item 15), and results from analyses (items17 and 18) were also generally included. In addition alldiscussion items, including interpretation of results (item 20)within the context of current evidence (item 22) and externalvalidity (item 21). However, there were several areas wherereporting could be improved, including sample size (item 7),randomization sequence allocation (item 8), allocation con-cealment (item 9), and implementation (item 10), blinding(item 11), recruitment (item 14), numbers analyzed (item 16),and adverse events (item 19).

Table 4Effect of administration of HS extract on animal total cholesterol, HDL-C, LDL-C and triglycerides.

Primary author,year

Condition Samplesize

PlantPart

Extractmode

Dose End timepoint

Withingroup TC

Betweengroup TC

Within groupHDL-C

Between groupHDL-C

Within groupLDL-C

Between groupLDL-C

Withingroup TG

Betweengroup TG

Olatunji, 2005 None 6 rats Pa W 1a 28 NS NS Dep NSOlatunji, 2005 None 6 rats Pb W 1a 28 NS NS Dep NSOlatunji, 2005 None 6 rats Pa W 1.5a 28 Dep NS Dep NSOlatunji, 2005 None 6 rats Pb W 1.5a 28 Dep NS Dep NSFarombi, 2007 None 5 rats F A 100a 28 NS NS N/A NSFarombi, 2007 None 5 rats F A 200a 28 Dep NS N/A DepPeng, 2011 None 8 rats C A 200a 63 NS N/A N/A NSChen, 2003 Hyper 6 rabbits N/A W 0.5b 70 Dep NS Dep DepChen, 2003 Hyper 6 rabbits N/A W 1b 70 Dep NS Dep DepEl-Saadany, 1991 Hyper 6 rats C N/A 5b 63 Dep N/A N/A DepEl-Saadany, 1991 Hyper 6 rats C N/A 10b 63 Dep N/A N/A DepHirunpanich, 2006 Hyper 6 rats C W 250a 42 NS Dep NS NS NS Dep NS NSHirunpanich, 2006 Hyper 6 rats C W 500a 42 Red Dep NS NS Red NS Red DepHirunpanich, 2006 Hyper 6 rats C W 1000a 42 Red Dep NS NS Red Dep Red NSChen, 2004 Hyper 6 rats F W 10000a 84 Dep NS Dep NSChen, 2004 Hyper 6 rats F W 20000a 84 Dep NS Dep NSCarvajal-Zarrabal, 2005 Hyper N/A rats C A 5c 28 Dep NS Dep DepCarvajal-Zarrabal, 2005 Hyper N/A rats C A 10c 28 NS NS Dep DepCarvajal-Zarrabal, 2005 Hyper N/A rats C A 15c 28 NS NS Dep DepPeng, 2011 Hyper 8 rats C A 100a 63 NS N/A N/A DepPeng, 2011 Hyper 8 rats C A 200a 63 Dep N/A N/A DepOchani, 2009 Hyper 6 rats C A 500a 30 Dep Ele Dep DepGosain, 2010 Hyper 6 rats L A 100a 28 NS NS NS NS NS NS NS NSGosain, 2010 Hyper 6 rats L A 200a 28 Red Dep NS NS Red Dep Red DepGosain, 2010 Hyper 6 rats L A 300a 28 Red Dep NS NS Red Dep Red DepOchani, 2009 Hyper 6 rats L A 500a 30 Dep Ele Dep DepFarombi, 2007 Diab 5 rats F A 100a 28 Dep NS N/A NSFarombi, 2007 Diab 5 rats F A 200a 28 Dep NS N/A NSLee, 2009 Diab 5 rats F A 100a 56 Dep NS Dep DepLee, 2009 Diab 5 rats F A 200a 56 Dep NS Dep DepPeng, 2011 Hyper, diab 8 rats C A 100a 63 NS N/A N/A DepPeng, 2011 Hyper, diab 8 rats C A 200a 63 Dep N/A N/A Dep

Notes: Condition: Hyper=hyperlipidemia, Diab=diabetes; Plant part used in extract: P=petal, F=flower, C=calyx, L=leaf, a=red, b=green; Extract mode: W=water, A=alcohol; Dose: a=mg of HS extract/kg weightof animal/day, b=%, c=g extract/100 g basal diet; End time point: number of days after start of treatment when measurement was taken; TC=total cholesterol, HDL-C=high-density lipoprotein cholesterol, LDL-C=low-density lipoprotein cholesterol, TG=triglycerides; Results: N/A=not available, NS=not significant, Dep=depressed, Ele=elevated, Red=reduced, Inc=increased, Depressed or elevated used when valuescompared with appropriate control, increased or reduced used when values compared between baseline and end of treatment within the same group.

90A.L.H

opkinset

al./Fitoterapia

85(2013)

84–94

Table5

CholesterolR

CTinterven

tion

san

deffectsof

cholesterolR

CTinterven

tion

son

totalc

holesterol,H

DL-C,

LDL-C,

andtriglyceride

s.

Prim

aryau

thor,y

ear

Cond

ition

Sample

size

Subs

tanc

ePlan

tpa

rtEx

tract

mod

eDose

#of

doses

perda

yDay

sdo

setake

nTC

(SD)

p-va

lue

HDL-C

(SD)

p-va

lue

LDL-C

(SD)

p-va

lue

TG(SD)

p-va

lue

Moh

aghe

ghi,20

11Hyp

erten

45(4

2)HS

CW

.015

/2a

20

206(3

9)44

.3(8

.3)

130.8(2

9)15

3.5(5

9)15

212(3

7)Inc

46(7

.2)

Inc

133.2(2

6)NS

157.5(5

8)NS

Gurrola-D

iaz,

2010

Non

e26

(26)

HS

CA

100b

10

202.6(4

1.6)

41.6

(10.3)

124.1(4

1.7)

148.0(6

1.3)

3019

7.5(3

7.0)

NS

45.8

(9.3)

Inc

124.5(3

5.5)

NS

113.8(5

4.1)

Red

Gurrola-D

iaz,

2010

MeS

y18

(18)

HS

CA

100b

10

199.8(4

0.5)

32.0

(5.8)

130.1(3

4.8)

172.3(1

07.4)

3017

9.7(2

1.2)

Red

44.5

(8.3)

Inc

104.1(2

0.4)

Red

137.6(6

2.1)

NS

Kuriyan

,201

0Hyp

erlip

30(2

8)HS

LA

500b

20

207.1(3

2.5)

42.0

(9.4)

155.3(1

3.9)

159.9(9

0.6)

9019

8.5(3

3.2)

NS

42.6

(8.9)

NS

127.6(2

4.1)

Red

143.3(7

3.9)

Red

Moz

affari-K

hosrav

i,20

09Diab

30(2

7)HS

CW

2/24

0c2

023

6.2(5

8.1)

48.2

(10.6)

137.5(5

3.4)

246.1(8

4.9)

3021

8.6(3

8.4)

Red

56.1

(11.3)

Inc

128.5(4

1.2)

Red

209.2(5

7.2)

Red

Lin,

2007

Hyp

erlip

14(N

/A)

HS

FW

500b

30

201.9(2

7.2)

2819

4.6(2

4.2)

Red

Lin,

2007

Hyp

erlip

14(N

/A)

HS

FW

500b

60

223.4(3

6.8)

2821

3.9(3

7.0)

Red

Lin,

2007

Hyp

erlip

14(N

/A)

HS

FW

500b

90

207.5(2

6.5)

2821

2.6(4

0.0)

NS

Notes:C

ondition

:Hyp

erten=

hype

rten

sion

,MeS

y=

metab

olicsynd

rome,Hyp

erlip

=hy

perlipidem

ia,D

iab=

diab

etes;S

amplesize:b

eginning

ofstud

y(end

ofstud

y),N

/A=

nota

vaila

ble;

Substanc

e:HS=

Hibiscussab

dariffa

;Plant

part

used

inex

tract:

C=

calyx,

L=leaf,F

=flo

wer;Ex

tractmod

e:W

=water,A

=alco

hol;Dose:

a=

gsu

bstanc

e/glassof

extraction

substanc

e,b=

mgof

HSex

tract,

c=

gof

substanc

e/mLof

extraction

substanc

e;TC

=total

cholesterol,HDL-C=

high

-den

sity

lipop

rotein

cholesterol,LD

L-C=

low-den

sity

lipop

rotein

cholesterol,TG

=triglyceride

s,SD

=stan

dard

deviation;

Results:

NS=

notsign

ificant,R

educ

ed=

Red,

Increa

sed=

Inc,

increa

sedor

redu

cedus

edwhe

nva

lues

compa

redbe

twee

nba

selin

ean

den

dof

treatm

entwithinthesamegrou

p.

91A.L. Hopkins et al. / Fitoterapia 85 (2013) 84–94

More specifically, most studies did not make clear thetype of RCT being conducted and in many cases there werestudy design problems. In several RCTs black tea was used asthe comparator, as opposed to a placebo, making the resultsdifficult to interpret because of the active pharmacologicalproperties of black tea [10,12,14,18]. McKay and colleagues[8] in the only placebo-controlled trial to date provided anotable exception to this trend by using a placebo drink thatwas non-active and is used in the beverage industry to mimicthe flavor of HS tea in commercially prepared drinks. In somecomparative effectiveness trials it was difficult to compareeffectiveness between treatments because the medicationwas not administered as directed by doctors [11], whereasother trials provided realistic comparators [13,16]. Theresults from the study on dose response are difficult tointerpret because the baseline values for total cholesteroldiffered substantially between groups [15].

Additionally, there were several problems specific to thecholesterol RCTs. Differences between groups were impossibleto assess because none of the studies included effect sizes orstatistical analyses of the between-group differences [14–18].Another problem with most of the cholesterol trials was shortstudy duration with 4 trials lasting 15 days [18] to 30 days[14–16] and only one trial of a longer 90 day duration [17]. Ingeneral, lipid profiles can take up to 2 months to reflectmeaningful change in patients given statin medication ormodifications to their diet and lifestyle [55,56]. The hyperten-sion trials selected patient populations with mild to moderatehypertension [8,11–13] with only one study providing theadditional condition of diabetes [10], whereas the patientpopulations in the cholesterol trials had an array of conditions,many of which did not include elevated cholesterol [14,16,18],making it difficult to assess the effectiveness of HS in treatinghyperlipidemia.

The quality scores for items specific to the herbal interven-tion were much lower, ranging from 28% [12] to 67% [8] forthe hypertension RCTs and from 33% [18] to 65% [15,16] for thecholesterol RCTs. Reporting was particularly lacking in theherbal description in the title or abstract (item 1), descriptionof how traditional theories and concepts were maintained,including traditional preparation and dosing practices (item3),all aspects of the intervention (items 4a, 4c–4f), exceptcharacteristics of the herbal product (item 4b), concomitantmedications (item 15), interpretation in the light of theproduct and dosage regimen used (item 20) and how theherbal product and dosage regimen used relates to self-care(item 21).

There were also several problems with the preparation ofHS. Many of the studies did not report the part of the plantthat was used in the preparation. Kuriyan and colleagues [17]used the leaves in their extract without explanation, whereasthe calyxes are most commonly used in HS preparations. Inaddition, the amount of HS used in preparations and the doseadministered varied greatly with Mohagheghi and colleagues[18] choosing to use an extremely small amount of HScalyxes in the preparation per dose and many of the studiesfailing to include any measure of marker constituents. Theabsence of information related to product content and themethod of preparation and the lack of uniformity of extractsmade it difficult to compare findings between studies. Inaddition, the lack of information regarding ethnobotanical

Table 6Quality of RCT reporting.

Primary author, year CONSORT2001 (%)

CONSORT HerbalInterventionsElaboration (%)

McKay, 2010 95.45 66.67Haji, 1999 81.82 27.78Mozaffari-Khosravi, 2009 81.82 50.00Herrera-Arellano, 2004 81.82 60.00Herrera-Arellano, 2007 68.18 55.00Mohagheghi, 2011 63.64 33.33Gurrola-Diaz, 2010 63.64 65.00Kuriyan, 2010 72.73 50.00Mozaffari-Khosravi, 2009 81.82 38.89Lin, 2007 59.09 65.00

92 A.L. Hopkins et al. / Fitoterapia 85 (2013) 84–94

use made it difficult to determine the relationship betweenthe studies and traditional therapeutic use.

9. Biological mechanisms

In vitro and in vivo studies focused on mechanism of actionhave determined several potential mechanisms of the HSextracts that may explain the hypotensive activity, including(1) vasodilation mediated through endothelium-derived re-laxant pathways and inhibition of calcium influx [9,57], (2) ACEinhibition [9] by the stimulation of new vessel formation and areduction of myocardial mass [52] or anthocyanins competingwith the substrate for the active site [58], (3) decrease in bloodviscosity through cyclooxygenase inhibitory activity [44], and(4) inhibition of adipocyte differentiation through the modu-lation of PI3-K/Akt and ERK pathway [59].

Other potential mechanisms have been tested to explainthe positive impact of HS extract on cholesterol metabolism.For example, cholesterol biosynthesis may be reduced byinhibiting HMG-CoA reductase [42,60]. Decreases in LDL-Cmay be the result of the inhibition of triacylglycerol synthesisby hibiscus acid racemization [43]. The positive effects of theextract in diabetic animal models may be partially the resultof the reduction in the expression of CTGF and RAGE [30].Additionally, although not directly related to the reductionin cholesterol but beneficial for improving cardiovascularrisk factors, HS may hinder atherosclerosis and improvevasoreactivity through (1) impediment of the formation ofmacrophage-derived foam cells [61] and/or (2) inhibition ofLDL-C oxidation due to antioxidant effects of the extract[25,28,29,31,53,54].

10. Conclusions

There are many strengths and limitations to the array ofevidence considered in this review. Ethnomedicinal studiesprovide evidence for the widespread use of a tea made withHS calyxes to treat hypertension and hyperlipidemia, butthese studies provide little guidance for animal and humanstudies through their lack of attention to cultivation,preparation, and consumption patterns.

HS extracts are generally considered to have a low degreeof toxicity. Studies demonstrate that HS consumption doesnot adversely effect liver and kidney function at lower doses,but may be hepatotoxic at extremely high doses. In addition,

electrolyte levels generally are not effected by ingesting HSextracts despite its diuretic effects.

Animal studies have consistently shown that consumptionof HS extract reduces blood pressure in a dose dependentmanner. They have also shown that total cholesterol, LDL-C, andtriglycerides were lowered in the majority of normolipidemic,hyperlipidemic, and diabetic animal models, whereas HDL-Cwas generally not affected by the consumption of HS extract.

The daily consumption of HS calyx extracts significantlylowered SBP and DBP in adults with pre to moderate essentialhypertension and type 2 diabetes. In addition, HS tea was aseffective at lowering blood pressure as Captropril, but lesseffective than Lisinopril. Over half of the RCTs showed thatdaily consumption of HS tea or extracts had a favorableinfluence on lipid profiles including reduced total cholesterol,LDL-C, triglycerides as well as increased HDL-C. Regrettablymany of the RCTs were of low quality and did a poor jobcharacterizing the HS extracts and utilized a form that is notwidely consumed making it difficult to determine the amountof public health benefit related to HS tea consumption. McKayand colleagues [8] provide a notable exception with their highquality placebo-controlled trial. As the findings related to theeffects of HS on blood pressure from lower quality studies areconsistent with those of this high quality study, the totality ofevidence suggests that HS consumption may have a publichealth benefit due to its anti-hypertensive effects.

Anthocyanins found in abundance in HS calyxes aregenerally considered the phytochemicals responsible for theantihypertensive and hypocholesterolemic effects, howeverevidence has also been provided for the role of polyphenolsand hibiscus acid. A number of potential mechanisms havebeen proposed to explain the hypotensive and anticholesteroleffects, but the most common explanation is the antioxidanteffects of the anthocyanins inhibit LDL-C oxidation whichimpedes atherosclerosis, an important cardiovascular riskfactor. Research on active compounds in HS and the mecha-nisms of action are still fairly nascent making it difficult tojustify carrying out RCTs using anything other than the wholeplant parts used in general practice.

This body of evidence interpreted together suggests thatHS has great potential to reduce risk factors associated withcardiovascular disease and merits further study.

Acknowledgements

This research was funded by the National Center forComplementary and Alternative Medicine at the NationalInstitutes of Health grant (T32AT001287). The funders had noinvolvement in the preparation or writing up of this research.

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