Herbal Hypolipidaemics: an overview of

worldwide research on hypolipidaemic herbs

Dr Rafe Bundy PhD RNutr

School of Food Biosciences
University of Reading
 Presentation 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
and 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)

Transport

Steroid hormones
Bile Cell membranes Hormones/
Androgens/Oestrogens
Phospholipids
Energy
Cell membranes Glucorticoids Bile salts messengers
Free cholesterol Glycoplipids
Mineralocorticoids Free cholesterol Prostaglandins
Vitamin D

General lipoprotein
structure
Chylomicrons
VLDL
LDL, HDL
 Daily Cholesterol Flux through the body

GI Tract
GI Tract

1g Turnover Total Body Pool Bile

Dietary
0.4g Plasma 5g (excl. plasma) 19g Faecal
Cholesterol 8g Losses
CM
VLDL 132g
LDL
0.6g HDL 1g

De novo
synthesis
(HMG CoA Reductase)
Hypolipidemic herbs : review
of the human literature
 Hypolipidemic 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
Garlic
Allium 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
Garlic:
Garlic RCT trials for serum cholesterol reduction
(based on Banerjee and Maulik (2003) Nutrition Journal. 1: p1-14 )

 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

 Garlic: Meta-analyses for serum cholesterol reduction
Analysis Studies Setting Outcome
Warshafsky 5 RCT trials N=324 TC↓9% approx.
et al (1993) TC > 5.17 mmol/l (significant) with garlic
0.5 to 1 clove/d
Slagy and 16 trials (not all N=952 TC↓12% approx.
Neil (1994) RCT) TC 6.4 mmol/l approx (significant)
Neil et al 17 trials (same as N=1067 TC↓10% approx.
(1996) 1994 but including TC > 6.4 mmol/l approx (significant)
1 new trial)
Stevinson et 13 RCT trials N=796 TC↓6% approx.
al (2000) + (included 5 new TC 7.1 mmol/l approx (significant)
trials from 1996)

+
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.

Guggul
Commiphora 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 Guggul sterones TC↓ 25.2
TC 6.3 mmol/l (100mg/d) or placebo
***** LDL↓ 16.9
(Hypercholesterolemia) 24 weeks

Kuppurajan et al N=40 Gum guggul (6g/d) TC ↓ 17.5

(1978) TC Not specified Guggulu Fraction A (1g/d) TC ↓ 4.4
Clofibrate (1.5g/d) TC ↓ 2.4
***** (Obesity)
Placebo 3 weeks TC ↓ 11.8
N=40 Gum guggul (6g/d) TC ↓ 23
TC >7.8 mmol/l Guggulu Fraction A (1g/d) TC ↓ 51
Clofibrate (1.5g/d) TC ↓ 55
(Hypercholesterolemia)
Placebo 3 weeks TC ↓ 35
N=40 Gum guggul (6g/d) TC ↓ 20
TC Not specified Guggulu Fraction A (1g/d) TC ↑ 14
Clofibrate (1.5g/d) TC ↓ 19
(Hyperlipidemia)
Placebo 3 weeks TC ↓ 21

Szapary et al N=103 Guggul sterones No significant

(2003) *** TC Not specified (75 or 150mg/d) or changes
(Hyperlipidemia) placebo
8 weeks
 Guggul: RCT trials for serum cholesterol reduction (2)
Study Subjects Treatment Changes from
baseline (%)
Verma and Bordia N=40 Purified Gum Guggul TC↓ 21.9
(1998) TC 7.1 mmol/l (4.5g/d) or placebo
HDL↑ 35.8
(Hyperlipidemia) 16 weeks
* LDL↓ 36.3
Bordia and N=20 Gum Guggulu Fraction A TC ↓ 8.7
(1g/d) or placebo
Chuttani (1979) TC 5.8 mmol/l
4 weeks
* (Healthy)
N=20 Gum Guggulu Fraction A TC ↓ 7.3
(1g/d) or placebo
TC 7.2 mmol/l
20 weeks
(Coronary Artery Disease)
Malhotra and N=44 Gum Guggulu Fraction A TC ↓ 27
(1g/d)
Ahuja (1971) TC Not specified TC ↓ 24
EPC (1.5g/d)
* (Hyperliproteinemia) Ciba (300mg/d)
TC ↓ 46
6-34 weeks

SUMMARY – Six trials involving 388 patients suggest TC↓ 7% to 27% over baseline
Fenugreek Seeds
Trigonella 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 reduction
Study Subjects Treatment Changes from
Baseline (%)
Singh et al N=92 Fenugreek (60g/d) TC↓15.4 HDL ↓3.6 LDL↓18.8
(1998) TC Not specified Triphala (6g/d) TC↓4.7 HDL ↑ 5.3 LDL↓7.2
(Hypercholesterolemia) Placebo
****
12 weeks
Prasanna N=18 Fenugreek (50g/d) TC↓26.1 HDL ↓6.7 LDL↓30.6
(2000) TC Not specified Fenugreek (100g/d) TC↓33.1 HDL ↑3.0 LDL↓38.2
Placebo
** (Obesity)
3 weeks

Sharma and N=15 Fenugreek (100g/d) or no TC↓16.7

supplementation
Raghuram TC 4.5 mmol/l
1.5 weeks
(1990) ** (NIDDM)

Sharma and N=5 Fenugreek (100g/d) or no TC↓21.0

supplementation
Raghuram TC Not specified
3 weeks
(1990) ** (NIDDM)
Sharma et al N=10 Fenugreek (100g/d) or no “TC and LDL significantly
supplementation reduced…compared to
(1990) * TC Not specified
1.5 weeks the control diet”
(NIDDM)

SUMMARY – Five trials involving 140 patients suggest TC↓ 15% to 33% over baseline
Red Yeast Rice
Monascus 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 N=14 Red Yeast Rice (2.4g/d) TC↓30.8 LDL↓32.3
(2002) TC 5.4 mmol/l Placebo TC↓7.7 LDL↓26.3
(HIV-related 8 weeks
*** dyslipidemia)
Heber et al N=83 Red Yeast Rice (2.4g/d) TC↓16.1 LDL↓21.9
(1999) TC 6.5 mmol/l Placebo TC↓1.8 LDL↓2.6
(Healthy) 12 weeks
***
Shen et al N=152 Red Yeast Rice (5.0g/d) TC↓19.2 HDL↑ 16.7 LDL↓ 27
(1996) ** TC >6.5 mmol/l or control TC↓1.5 LDL↑ 2.4
(Hypercholesterolem 8 weeks
ia)
Wang et al N=446 Red Yeast Rice (2.4g/d) TC↓22.9 HDL↑19.9LDL↓31.7
Jiagulan (1.2g/d) TC↓6.7 HDL↑ 8.4 LDL↓ 8.3
(1997) * TC >5.9 mmol/l
(Hyperlipidemia)

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 N=36 Egg Plant (2% w/v infusion) TC↓6.8 HDL↑ 13.6 LDL↓1.5
al (2000) TC >6.4 mmol/l Placebo TC↓4.4 HDL↓ 2.3 LDL↓13.5
(Hypercholesterolemia 5 weeks
*** )
N=16 Egg Plant TC↑ 23 HDL↑10 LDL↑15
TC >6.4 mmol/l Placebo TC↓7.4 HDL↑4 LDL↓8
(Hypercholesterolemia 5 weeks
)
Diet recommendations
Gupta et al N=105 Arjun (500 mg/d) TC↓9.7 HDL↓4.1 LDL↓15.8
(2001) *** (Coronary Artery Vitamin E TC↓2.6 HDL↑9.1 LDL↓7.9
Disease) Placebo TC↑8.5 HDL↑8.3 LDL↑12.5
4 weeks
Sotaniemi et N=36 Asian Ginseng (100mg) No change TC, HDL, LDL
al (1995) ** (NIDDM) Asian Ginseng (100mg)
Placebo
8 weeks
Other herbs: RCT trials for serum cholesterol reduction (2)
Study Subjects Treatment Changes from
Baseline (%)
Agarwal et al N=40 Holy Basil TC↓ 7.6
(1996) TC >6.4 mmol/l Placebo TC↑ 1.3
(Hypercholesterolemia 8 weeks
** )
(NIDDM)
Asgary et al N=20 Yarrow (Achillea wilhelmsii) TC↓39 HDL↑20.4 LDL↓35.6
(2000) *** (Hypercholesterolemia Placebo TC↑ 4.6 HDL↓4.3 LDL↑ 3.4
) 24 weeks

Petronelli et N=20 Silymarin TC↑ 2.6

al (1981) * (Dyslipidemia) Placebo TC↓ 0.3
8 weeks

Stannols/Sterols: plant components that have been

shown to reduce TC and LDL by 10 –15%
www.consumerlab.com
Artichoke
Cynara scolymus

Artichoke Leaf Extract (ALE) contains cynarin

and luteolin
 Globe 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 Constituents
 Caffeoylquinic acids
 e.g. Cynarin, chlorogenic acid

 Flavonoids
 e.g. Luteolin and derivatives

 Bitters
 e.g. Cynaropicrin
 ALE – Metabolic Actions

Hepatoprotective
(similar to Milk Thistle) Anti-atherogenic
cholesterol
elimination (bile)
cholesterol
synthesis
LDL oxidation
Choleretic
bile secretion

Carminative, Spasmolytic, Anti-emetic

 ALE – previous human studies
Study Subjects Treatment Change from
Baseline (%)
Fintelmann & N=302 Av. 1520 mg/d
Menssen (1996) Total Chol. 6.86 mmol/ Artichoke extract Total Chol. 11.5%
Post-Marketing Trial Dyspepsia 6 weeks
Fintelmann & N=171 Av. 1600 mg/d Total Chol. 10.9%
Petrowicz (1998) Total Chol. 6.31 mmol/l Artichoke extract LDL Chol. 15.8%
Post-Marketing Trial Dyspepsia 6 months LDL/HDL 21%

N=59 (subset) Total Chol. 15.1%

LDL Chol. 20.8%
Total Chol. >6.76 mmol/l
Petrowicz et al N=44 1920 mg/d No significant differences
(1997) RCT Total Chol. <5.4mol/l? Artichoke extract vs.
Abstract only Healthy placebo
12weeks
Englisch et al (2000) N=143 1800 mg/d Total Chol. 18.5% vs.8.6%
RCT Total Chol. >7.28 mmol/l standardised dry LDL Chol. 22.9% vs. 6.3%
Hypercholesetrolemia extractvs. placebo LDL/HDL 20.2% vs. 7.2%
6 weeks
The ALE and Cholesterol Study
 The ALE and Cholesterol Study:
Aims 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:
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:
Outcome Measures
 Primary
 Total cholesterol
 LDL- and HDL- cholesterol
 LDL oxidation
 Triglycerides

 Secondary
 Plasma C-reactive protein, Bowel Health and
Quality of Life
 Summary
 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
Possible actions of herbs on cholesterol flux

Inhibit
GI Tract
Absorption GI Tract
Stannols
Fenugreek
1g Turnover Total Body Pool Bile
Dietary Plasma 5g (excl. plasma) 19g Faecal
Cholesterol 8g Losses
0.4g
132g
0.6g 1g

De novo Inhibit
Promote
synthesis Reabsorption
Secretion
Inhibit Fenugreek
ALE
Synthesis Garlic
ALE Guggul
Garlic
Red Yeast Rice
Guggul
 Summary
 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 TAG uptake Release of Fatty (HMG CoA Reductase
into liver/muscle into adipose tissue Acids into plasma to produce cholesterol)
 Acknowledgements
 Dr Ann Walker, Dr Steve Hicks
 University of Reading
 Dr Hugh Simpson, Dr David Williams
 Royal Berkshire Hospital
 Dr Dick Middleton
 Lichtwer Pharma Ltd.