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Herbal Hypolipidaemics: an overview of Herbal Hypolipidaemics: an overview of
worldwide research on hypolipidaemic herbsworldwide research on hypolipidaemic herbs
Dr Rafe Bundy PhD RNutr
School of Food Biosciences
University of Reading
Presentation PlanPresentation Plan
Coronary Heart Disease and Cholesterol Hypolipidemic herbs : review of the human
literature Garlic, Guggul, Fenugreek, Red Yeast Rice, Artichoke
A new study of Artichoke: The ALE and Cholesterol Study
Coronary Heart Disease Coronary Heart Disease and Cholesteroland Cholesterol
Coronary Heart Disease is a BIG killer More than 1.4 million people in the UK suffer from angina 300,000 people have a heart attack each year Kills more than 110,000 people a year in England Cost impact to UK economy in 1999 about £7 billion
Primary cause of CHD is Atherosclerosis, linked to high blood cholesterol.
18 %and 22.4 %in UK have total cholesterol >6.5mmol/l (DoH 1998)
www.heartstats.org
Total Cholesterol is made up of Low Density Lipoprotein (LDL) Cholesterol High Density Lipoprotein (HDL) Cholesterol Other (Chylomicrons and VLDL)
The concentration of LDL and the ratio LDL/HDL is probably more important than the Total
Suggested healthy levels LDL-Cholesterol < 3.0-4.0mmol/l? HDL-Cholesterol >0.9 mmol/l LDL/HDL <3.0
Cholesterol Triacylglycerol (TAG)
Cell membranesFree cholesterol
Steroid hormones Androgens/Oestrogens
GlucorticoidsMineralocorticoids
Vitamin D
BileBile salts
Free cholesterol
Cell membranesPhospholipidsGlycoplipids
Hormones/messengersProstaglandins
Energy
General lipoprotein structure
ChylomicronsVLDL
LDL, HDL
Transport
Plasma
8g
Total Body Pool (excl. plasma)
132g
De novosynthesis
Dietary Cholesterol
1g
0.6g
0.4g 5gTurnover Bile
19g
(HMG CoA Reductase)
CMVLDLLDLHDL
FaecalLosses
1g
Daily Cholesterol Flux through the bodyDaily Cholesterol Flux through the body
GI TractGI Tract
Hypolipidemic herbs :Hypolipidemic herbs : review review of the human literatureof the human literature
Hypolipidemic Herbs: Literature ReviewHypolipidemic Herbs: Literature Review(based on Thompson and Ernst (2003) J Fam Prac. 52: p468-78 )
Randomized controlled trials in Humans Garlic (Allium satvium) Guggul (Commiphora mukul) Fenugreek (Trigonall foenum-graecum) Red yeast Rice (Monascus purpureus) Artichoke (Cynara scolymus)
In brief Yarrow (Achillea wilhelmsii), Holy Basil (Ocimum
sanctum), Eggpalnt (Solanum melongena), Arjun (Terminalia arjun), stannols
GarlicAllium satvium
Important to the ancient Egyptians and listed in their medical text Codex Ebers
Contains many important compounds including: allicin, S-allyl cysteine, diallyl-di-sulphide
46 Human studies since 1975 Most used garlic powder for 4 to 16 weeks Most show significant↓in TC and TAG LDL↓ 11 to 26 % (measured one-third of studies)
18 Human studies since 1993-2002 9 show NO effect on cholesterol Differences in composition may explain some
differences?
4 meta-analyses are available
GarlicGarlic: RCT trials for serum cholesterol reductionreduction (based on Banerjee and Maulik (2003) Nutrition Journal. 1: p1-14 )
Garlic: Meta-analyses for serum cholesterol reduction
Analysis Studies Setting Outcome
Warshafsky et al (1993)
5 RCT trials N=324TC > 5.17 mmol/l
TC↓9% approx. (significant) with garlic 0.5 to 1 clove/d
Slagy and Neil (1994)
16 trials (not all RCT)
N=952TC 6.4 mmol/l approx
TC↓12% approx. (significant)
Neil et al (1996)
17 trials (same as 1994 but including
1 new trial)
N=1067TC > 6.4 mmol/l approx
TC↓10% approx. (significant)
Stevinson et al (2000) +
13 RCT trials (included 5 new trials from 1996)
N=796TC 7.1 mmol/l approx
TC↓6% approx. (significant)
+ Conclusion: Garlic is superior to placebo – but the size of the effect is modest, and the robustness of the effect debateable. May in part be due to differences in Allicin yield?
Garlic: Summary of 13 RCT trials
From: Stevinson et al. (2000) Ann Intern Med. 19;133(6):420-9.
GuggulCommiphora mukul
Sticky gum resin from the mukul myrrh tree contains sterols guggulsterones E and Z
Guggul: RCT trials for serum cholesterol reduction (1)
Study Subjects Treatment Changes from baseline (%)
Singh et al (1994)
*****
N=61
TC 6.3 mmol/l
(Hypercholesterolemia)
Guggul sterones (100mg/d) or placebo
24 weeks
TC↓ 25.2
LDL↓ 16.9
Kuppurajan et al (1978)
*****
N=40
TC Not specified
(Obesity)
Gum guggul (6g/d)
Guggulu Fraction A (1g/d)
Clofibrate (1.5g/d)
Placebo 3 weeks
TC ↓ 17.5
TC ↓ 4.4
TC ↓ 2.4
TC ↓ 11.8
N=40
TC >7.8 mmol/l
(Hypercholesterolemia)
Gum guggul (6g/d)
Guggulu Fraction A (1g/d)
Clofibrate (1.5g/d)
Placebo 3 weeks
TC ↓ 23
TC ↓ 51
TC ↓ 55
TC ↓ 35
N=40
TC Not specified
(Hyperlipidemia)
Gum guggul (6g/d)
Guggulu Fraction A (1g/d)
Clofibrate (1.5g/d)
Placebo 3 weeks
TC ↓ 20
TC ↑ 14
TC ↓ 19
TC ↓ 21
Szapary et al (2003) ***
N=103
TC Not specified
(Hyperlipidemia)
Guggul sterones
(75 or 150mg/d) or placebo
8 weeks
No significant changes
Guggul: RCT trials for serum cholesterol reduction (2)
Study Subjects Treatment Changes from baseline (%)
Verma and Bordia (1998)
*
N=40
TC 7.1 mmol/l
(Hyperlipidemia)
Purified Gum Guggul (4.5g/d) or placebo
16 weeks
TC↓ 21.9
HDL↑ 35.8
LDL↓ 36.3
Bordia and Chuttani (1979)
*
N=20
TC 5.8 mmol/l
(Healthy)
Gum Guggulu Fraction A (1g/d) or placebo
4 weeks
TC ↓ 8.7
N=20
TC 7.2 mmol/l
(Coronary Artery Disease)
Gum Guggulu Fraction A (1g/d) or placebo
20 weeks
TC ↓ 7.3
Malhotra and Ahuja (1971)
*
N=44
TC Not specified
(Hyperliproteinemia)
Gum Guggulu Fraction A (1g/d)
EPC (1.5g/d)
Ciba (300mg/d)
6-34 weeks
TC ↓ 27
TC ↓ 24
TC ↓ 46
SUMMARY – Six trials involving 388 patients suggest TC↓ 7% to 27% over baseline
Fenugreek SeedsTrigonella foenum-graecum
Used as a yang tonic in the Chinese tradition
Contains soluble fibre, galactomannose and alkaloids, most abundantly trigonelline
Fenugreek: RCT trials for serum cholesterol reductionStudy Subjects Treatment Changes from
Baseline (%)
Singh et al (1998)
****
N=92TC Not specified(Hypercholesterolemia)
Fenugreek (60g/d) Triphala (6g/d)
Placebo
12 weeks
TC↓15.4 HDL ↓3.6 LDL↓18.8
TC↓4.7 HDL ↑ 5.3 LDL↓7.2
Prasanna (2000)
**
N=18
TC Not specified
(Obesity)
Fenugreek (50g/d)
Fenugreek (100g/d)
Placebo
3 weeks
TC↓26.1 HDL ↓6.7 LDL↓30.6
TC↓33.1 HDL ↑3.0 LDL↓38.2
Sharma and Raghuram (1990) **
N=15
TC 4.5 mmol/l
(NIDDM)
Fenugreek (100g/d) or no supplementation
1.5 weeks
TC↓16.7
Sharma and Raghuram (1990) **
N=5
TC Not specified
(NIDDM)
Fenugreek (100g/d) or no supplementation
3 weeks
TC↓21.0
Sharma et al (1990) *
N=10
TC Not specified
(NIDDM)
Fenugreek (100g/d) or no supplementation
1.5 weeks
“TC and LDL significantly reduced…compared to the control diet”
SUMMARY – Five trials involving 140 patients suggest TC↓ 15% to 33% over baseline
Red Yeast RiceMonascus purpureus
Some ‘statins’ are based on the active component mevinolin
Red Yeast Rice: RCT trials for serum cholesterol reduction
Study Subjects Treatment Changes from Baseline (%)
Keithly et al (2002)
***
N=14TC 5.4 mmol/l(HIV-related dyslipidemia)
Red Yeast Rice (2.4g/d) Placebo
8 weeks
TC↓30.8 LDL↓32.3
TC↓7.7 LDL↓26.3
Heber et al (1999)
***
N=83
TC 6.5 mmol/l
(Healthy)
Red Yeast Rice (2.4g/d) Placebo
12 weeks
TC↓16.1 LDL↓21.9
TC↓1.8 LDL↓2.6
Shen et al (1996) **
N=152
TC >6.5 mmol/l(Hypercholesterolemia)
Red Yeast Rice (5.0g/d) or control 8 weeks
TC↓19.2 HDL↑ 16.7 LDL↓ 27
TC↓1.5 LDL↑ 2.4
Wang et al (1997) *
N=446
TC >5.9 mmol/l(Hyperlipidemia)
Red Yeast Rice (2.4g/d) Jiagulan (1.2g/d)
TC↓22.9 HDL↑19.9LDL↓31.7TC↓6.7 HDL↑ 8.4 LDL↓ 8.3
SUMMARY – Four trials involving 695 patients suggest TC↓ 16% to 31% over baseline
Other herbs
Other herbs: RCT trials for serum cholesterol reduction (1)
Study Subjects Treatment Changes from Baseline (%)
Guimaraes et al (2000)
***
N=36
TC >6.4 mmol/l(Hypercholesterolemia)
Egg Plant (2% w/v infusion)
Placebo
5 weeks
TC↓6.8 HDL↑ 13.6 LDL↓1.5
TC↓4.4 HDL↓ 2.3 LDL↓13.5
N=16
TC >6.4 mmol/l(Hypercholesterolemia)Diet recommendations
Egg Plant
Placebo
5 weeks
TC↑ 23 HDL↑10 LDL↑15
TC↓7.4 HDL↑4 LDL↓8
Gupta et al (2001) ***
N=105
(Coronary Artery Disease)
Arjun (500 mg/d)Vitamin EPlacebo4 weeks
TC↓9.7 HDL↓4.1 LDL↓15.8
TC↓2.6 HDL↑9.1 LDL↓7.9
TC↑8.5 HDL↑8.3 LDL↑12.5
Sotaniemi et al (1995) **
N=36
(NIDDM)
Asian Ginseng (100mg)Asian Ginseng (100mg)Placebo8 weeks
No change TC, HDL, LDL
Other herbs: RCT trials for serum cholesterol reduction (2)
Study Subjects Treatment Changes from Baseline (%)
Agarwal et al (1996)
**
N=40
TC >6.4 mmol/l(Hypercholesterolemia)
(NIDDM)
Holy Basil
Placebo
8 weeks
TC↓ 7.6
TC↑ 1.3
Asgary et al (2000) ***
N=20(Hypercholesterolemia)
Yarrow (Achillea wilhelmsii)Placebo24 weeks
TC↓39 HDL↑20.4 LDL↓35.6
TC↑ 4.6 HDL↓4.3 LDL↑ 3.4
Petronelli et al (1981) *
N=20
(Dyslipidemia)
SilymarinPlacebo8 weeks
TC↑ 2.6
TC↓ 0.3
Stannols/Sterols: plant components that have been shown to reduce TC and LDL by 10 –15%
www.consumerlab.com
ArtichokeCynara scolymus
Artichoke Leaf Extract (ALE) contains cynarin
and luteolin
Globe Artichoke - HistoryGlobe Artichoke - History
First described in 4th century BC Used in Europe since Roman times for
improving digestive and urinary tract health Used mostly for indigestion (dyspepsia) in
Germany/Switzerland Modern research has concentrated on
Artichoke Leaf Extract (ALE)
ALE – Key ConstituentsALE – Key Constituents
Caffeoylquinic acids e.g. Cynarin, chlorogenic acid
Flavonoids e.g. Luteolin and derivatives
Bitters e.g. Cynaropicrin
ALE – Metabolic ActionsALE – Metabolic Actions
Hepatoprotective(similar to Milk Thistle)
Cholereticbile secretion
Carminative, Spasmolytic, Anti-emetic
Anti-atherogeniccholesterol
elimination (bile)cholesterol synthesis
LDL oxidation
ALE – previous human studiesALE – previous human studies
Study Subjects Treatment Change from Baseline (%)
Fintelmann & Menssen (1996) Post-Marketing Trial
N=302 Total Chol. 6.86 mmol/ Dyspepsia
Av. 1520 mg/d Artichoke extract 6 weeks
Total Chol. 11.5%
Fintelmann & Petrowicz (1998) Post-Marketing Trial
N=171 Total Chol. 6.31 mmol/l Dyspepsia
Av. 1600 mg/d Artichoke extract 6 months
Total Chol. 10.9% LDL Chol. 15.8% LDL/HDL 21%
N=59 (subset) Total Chol. >6.76 mmol/l
Total Chol. 15.1% LDL Chol. 20.8%
Petrowicz et al (1997) RCT Abstract only
N=44 Total Chol. <5.4mol/l? Healthy
1920 mg/d Artichoke extract vs. placebo 12weeks
No significant differences
Englisch et al (2000) RCT
N=143 Total Chol. >7.28 mmol/l Hypercholesetrolemia
1800 mg/d standardised dry extractvs. placebo 6 weeks
Total Chol. 18.5% vs.8.6% LDL Chol. 22.9% vs. 6.3% LDL/HDL 20.2% vs. 7.2%
The ALE and Cholesterol StudyThe ALE and Cholesterol Study
The ALE and Cholesterol Study:The ALE and Cholesterol Study:Aims and DesignAims and Design
Does ALE significantly alter plasma lipid profile in adults with moderately raised cholesterol?
Randomised double-blind placebo controlled parallel trial 12 weeks intervention 1280 mg Cynara Artichoke vs. placebo
The ALE and Cholesterol Study:The ALE and Cholesterol Study: Study Group Study Group
70 otherwise healthy individuals Total cholesterol 6.0 to 8.0 mmol/l, aged 18-75
Recruitment RBH Pathology Laboratory database search Information sent to patient via GP Further blood test if patient interested Exclusions
Pregnancy, major organ pathology or major mental illness, drug or alcohol abuse, biliary obstruction, cholesterol lowering drugs, anti-coagulants.
Additional recruitment through press release
The ALE and Cholesterol Study:The ALE and Cholesterol Study: Outcome Measures Outcome Measures
Primary Total cholesterol LDL- and HDL- cholesterol LDL oxidation Triglycerides
Secondary Plasma C-reactive protein, Bowel Health and
Quality of Life
SummarySummary CHD is a big killer, a huge drain on the NHS, the
economy, and society
There is clinical data showing some herbs have strong hypercholesteremic actions
Plasma
8g
Total Body Pool (excl. plasma)
132g
De novosynthesis
Dietary Cholesterol
1g
0.6g
0.4g
5gTurnover Bile
19g FaecalLosses
1g
Possible actions of herbs on cholesterol fluxPossible actions of herbs on cholesterol flux
GI TractGI Tract
Promote Secretion
ALEGarlic
Guggul
Inhibit Reabsorption
FenugreekInhibit Synthesis
ALEGarlic
Red Yeast RiceGuggul
Inhibit Absorption
StannolsFenugreek
SummarySummary CHD is a big killer, a huge drain on the NHS,
the economy, and society
There is clinical data showing some herbs have strong hypercholesteremic actions
We are further investigating ALE on plasma cholesterol, plus LDL-oxidation, triglycerides, bowel health and QoL
Food for thought - the Insulin link
Some herbs may be beneficial in hyperlipidemia and insulin resistance– is there a common pathway?
INSULIN
Glucose uptake into liver/muscle
(HMG CoA Reductase to produce cholesterol)
TAG uptake into adipose tissue
Release of Fatty Acids into plasma
- ++ +
AcknowledgementsAcknowledgements
Dr Ann Walker, Dr Steve Hicks University of Reading
Dr Hugh Simpson, Dr David Williams Royal Berkshire Hospital
Dr Dick Middleton Lichtwer Pharma Ltd.