Making a real difference:

herbs for hypertension

- new research, case histories & integrative medicine

Dr Ann Walker
Senior Lecturer in Human Nutrition

Hugh Sinclair Unit of Human Nutrition

The University of Reading, UK

Member of the National Institute of Medical Herbalists

Member of the College of Practitioners of Phytotherapy
 Classification of hypertension (mm Hg)

Category Diastolic Systolic

Mild 90-99 140-159

Moderate 100-109 160-179

Severe >110 >180

UKPDS* <85 < 150

*, UK Prospective Diabetes Study Br Med J 1998; 317:703-713.

Nutritional background
to hypertension
 Hypertension: DASH diet study
❧ >400 people, RCT, multicentre study:-
1 A typical USA diet
2 Low fat, low dairy, high fruit & veg, low Na diet
3 Combination diet - as (2) above but including
low-fat dairy products
❧ Combination diet lowered BP significantly more
than the other two diets
❧ Ca is important for vascular tone and
myocardial function
*, Dietary Approaches to Stop Hypertension,
Sacks et al. (2001) N Engl J Med 344, 3.
Comparison of
systolic and diastolic
responses to the
DASH diets using
random zero and
24 hour
monitoring
Case study: hypertension on a low dairy diet

Patient First visit Diet

details Nov 02 Supplements/d
Herbs
IT, female, ↑ Bp two yrs ↑
dairy, ↓
salt
79 yrs, ago, saw ↓
seed oils
non- nutritionist
smoker, who 1g Ca+0.5g Mg,
good diet, prescribed 1g vit C
except low low dairy. 1g Omega-3
dairy Latest 'nurse' 360 mg Rutin
intake, readings
BMI 21, 140/80 !! Hawthorn
Yarrow,
PMH: Catarrh, Cramp bark,
fainting insomnia. Limeflowers
 IT: response to hypotensive treatment

220
200
Started bendrofluazide 5mg/d
180
160
Diastolic
140
Systolic
120
100
80 Stress caused
by husband’s
60
dementia
Nov Dec June Sept Jan April
Catarrh↓
2002 2003 2004 sleeping OK
 Hypertension: RCTs on magnesium

❧ Sweden 1994. 39 hypertensive patients taking beta-

blockers. 365 mg Mg (as aspartate)/day for 8 weeks
Significant decrease in systolic Bp
❧ Holland 1994. 91 women with hypertension. 480
mg Mg (as aspartate)/day for 6 mo. Sig. drop (mm
Hg) of 2.7 systolic and 3.4 mm diastolic Bp
❧ Japan 1998. 60 hypertensive subjects: 480 mg Mg
(as oxide)/d for 8 weeks. Showed Mg to marginally
lower BP
❧ Mg is important for vascular tone and myocardial
function. Some studies have shown no effect.
 Hypertension: RCTs on vitamin C

❧ Observational studies and small controlled trials

suggest an inverse correlation between vit C
intake or plasma vit C levels and hypertension.
● USA 1999: 39 on medication for Bp. 500 mg vitamin
C/d. Outcome: Bp reduced by 10%
● UK 2000: 40 elderly subjects: 500 mg vit C for 3
months. Outcome: modest lowering systolic Bp
● USA 2002. 31 patients: 500mg. 1g or 2 g vitamin C.
No dose effect, but all significantly reduced Bp after 1
month of treatment and this persisted until the end of
the trial.
❧ Some studies have shown no effect
 Hypertension: RCTs on omega-3

❧ Australia 1998: 69 overweight

hypertensives on drug treatment RCT
dietary fish to given >3 g omega-3 EFAs as
fish per day 16 weeks. Significant drop in
Bp compared with no fish
❧ USA 1993: Two meta-analysis concluded
that omega-3 gives a dose-related
significant drop in Bp in hypertensive
subjects.
Hypertension: RCTs etc on coenzyme Q10
● USA 1994: three clinic reports on a total of 559
patients concluded that CoQ10 in doses ranging
from 75 to 600 mg/day is safe and effective
adjuctive treatment to drugs for hypertension in a
broad range of cardiovascular diseases.
● India 1999: 59 patients with hypertension and
coronary heart disease: 120 mg/d for 8 weeks.
Significant reduction in systolic and diastolic blood
pressure in active group.
● USA 2001: 83 subjects with systolic hypertension:
120 mg/d for 12 weeks. Mean reduction of 18
mm Hg in active group.
 Hawthorn (Crataegus spp)
- history of medicinal use
1305: Petrus de Crescentis: gout
1695: recorded use for hypertension by an
anonymous healer (LeClerc, 1935)
1800s: used in Lorraine, France for insomnia,
palpitations
1907: Ellingwood: heart tonic
1900s: researched in Germany for cardio-
vascular disease
Hawthorn (Crataegus laevigata)
♦ Active constituents:
● flavonoids including vitexin

● procyanidins, epicatechins

♦ Physiological actions:
● antioxidant, antisclerotic, smooth muscle

relaxant, hypotensive, vasodilator

♦ Traditional medicinal use:
● hypertension, atherosclerosis, poor

circulation, heart disease (including angina,

arrhythmia)
 FAM-1 Study
♦ The effects of a daily supplement of
Magnesium (600 mg/day as MgO) and/or
Hawthorn extract (500 mg/day ≡ 2.5 g of
dried leaves and flowers) for the
treatment of mild hypertension in
otherwise healthy subjects
♦ No of volunteers: 36 (18M/18F)
♦ Duration: 10 weeks
Diastolic blood pressure of 36 mildly hypertensive
men and women after a daily supplement of
600 mg Mg and/or 500 mg of Hawthorn extract
Blood pressure (mmHg)

100
98
96
94
92
90 * Baseline
10 weeks
88 *
86
84
82
80
Placebo Mg Hawthorn Mg +
Hawthorn
*, P = 0.081 v. other treatments
Walker et al. 2002
 W ELL-BEI NG QUEST I ONN AI R E
Circle a number on each of the following scales to indicate how often you feel each
phrase has applied to you in the past seven days

All the time Not at all

1. I feel that I am useful and needed 3 2 1 0

2. I have crying spells or feel like it 3 2 1 0

3. I find I can think quite clearly 3 2 1 0

4. My life is pretty full 3 2 1 0

5. I feel downhearted and blue 3 2 1 0

6. I enjoy the things I do 3 2 1 0

7. I feel nervous and anxious 3 2 1 0

8. I feel afraid for no reason at all 3 2 1 0

9. I get upset easily and feel panicky 3 2 1 0

10. I feel like I am falling apart 3 2 1 0

11. I feel calm and can sit still easily 3 2 1 0

12. I fall asleep easily 3 2 1 0

 W ELL-BEI NG QUESTI ONN AI R E (cont.)

13. I feel energetic, active or vigorous 3 2 1 0

14. I feel dull or sluggish 3 2 1 0

15. I feel tired, worn out or exhausted 3 2 1 0

16. I have been waking up feeling fresh 3 2 1 0

17. I am happy and satisfied with my life 3 2 1 0

18. I feel well adjusted to my life situation 3 2 1 0

19. I live the kind of life I want to 3 2 1 0

20. I feel eager to tackle my daily tasks 3 2 1 0

21. I feel that I can easily handle any 3 2 1 0

serious problem or major change in my life

22. My daily life is full of things that are 3 2 1 0

interesting to me
 Mean anxiety score of 36 mildly hypertensive
subjects at baseline and after a daily supplement of
600 mg Mg and/or 500 mg of Hawthorn extract
6 *, P = 0.094 v. other treatments

4
Anxiety scores

3
*
*
2

0
0 w eek Placebo Mg Haw thorn Mg + Haw thorn
5 w eek Treatm ent
10 w eek Walker et al. (2002)
Hawthorn - action in heart disease

♦ Strengthens heart function

♦ Normalises blood pressure
♦ Lowers high blood cholesterol and
triglyceride levels
♦ Antioxidant - counters toxins
♦ Anti-clotting

Lowers risk of heart attack and

stroke
Insulin Resistance Syndrome (IRS)

♦ Linked to central obesity (apple-shape)

♦ HIGH CIRCULATING INSULIN
♦ Insulin resistance
♦ Raised blood glucose
♦ Increased blood triglyceride levels
♦ Reduced blood HDL cholesterol
♦ Increased blood pressure
 The FAM-2 study
♦ The effects of Hawthorn flavonoids (1200 mg
extract 5:1/day ≡ 6 g dried leaves and
flowers) for the treatment of high blood
pressure in type II diabetes
♦ Double-blind
♦ Parallel, placebo-controlled
♦ Number of volunteers: 80
♦ Duration of the study: 4 months, 3 clinic visits
♦ Intention-to-treat analysis
 FAM 2 recruitment criteria
♦ Male and female type II diabetic patients with
high blood pressure
♦ Diastolic BP: 85-100 mmHg
♦ Systolic BP: 145-170 mmHg
♦ Age: 35-75 yrs
♦ Volunteers encouraged to continue their drug
treatment (as prescribed by their GP) and
maintain their dietary and lifestyle habits
throughout the study
FAM 2 study group characteristics
Hawthorn Placebo
(n=39) (n=40)

Gender: M/F 27/12 28/12

Age mean 62.6 61.3
BMI kg/m2 28.8 30.2
%‘little exercise’ 60 55
%'not stressed' 42.5 55
% non-smokers 97.5 97.5
 Number of volunteers taking
hypoglycaemic drugs

Drug name Hawthorn Placebo

n = 39 n = 40
Insulin 4 3
Metformin 19 20
Gliclazide 12 16
Others* 6 7
Av. no. drugs/ 1.9 2.1
volunteer
* Glimepide, Glipizide, Rosigliclazide, Acarabose, or Glibenclamide
No. of volunteers taking hypotensive drugs
Drug group Hawthorn Placebo
n = 39 n = 40

ACE inhibitors 19 15
Ca channel blockers 8 10
ß-blockers 6 7
Diuretics 10 4
Angiotensin II recptr 2 4
antagonists &
other drugs
Average no. of 2.5 2.2
drugs/ volunteer
No. of volunteers taking other drugs
for CVD

Drug group Hawthorn Placebo

n = 39 n = 40

Statins 9 6

Aspirin 8 6

Clofibrates 1 3

Digoxin 0 1
 FAM2 study:
glycaemic control (group means)
10

9.5

9
HbA1c
8.5 *
Fasting glucose
8

7.5

7
Placebo Placebo Hawthorn Hawthorn
baseline month 4 baseline month 4
*, difference from baseline, p = 0.076; response diff from placebo, p = 0.070
 FAM2 study:
mean fructosamine and fibrinogen (mg/dL)
360
*
350

340
Fructosamine
330
Fibrinogen
320

310

300
Placebo Placebo Hawthorn Hawthorn
baseline month 4 baseline month 4
*, > baseline (p = 0.005)
 FAM 2 study:
mean blood pressure data
160
150
140
130
120 Diastolic
110 Systolic
100
90
80
*
70
Placebo Placebo Hawthorn Hawthorn
baseline month 4 baseline month 4
*, response p=0.035 cf placebo
 FAM 2 study:
Blood pressure: baseline - outcome
1 p=0.016 p=0.096 cf baseline
0.5
0
-0.5
-1
Diastolic
-1.5
Systolic
-2
-2.5
-3
-3.5
-4 p=0.035 cf placebo
Placebo Hawthorn
 FAM2 study:
lipid data - subset analysis
(Hawthorn n = 28, placebo n = 32):

4 Total chol
LDL chol
3
HDL chol
2 TAG
* *
1

0
Placebo Placebo Hawthorn Hawthorn
baseline month 4 baseline month 4
 FAM 2 study: subset analysis:
lipaemic control, baseline - outcome
0.4

0.3
Hawthorn

0.2 p=0.015 p=0.017 cf baseline

0.1 Total cholesterol

HDL chol
0 TAG
-0.1
Placebo
-0.2

-0.3
p=0.068 p=0.015 cf placebo
Fasting insulin: subset analysis
80
70
*
60
50
Baseline
40
After 4 months
30
20
10
0
Placebo (n = 20) Hawthorn (n = 21)
Insulin: % change from baseline
20

15 *
10

0
Placebo Hawthorn
-5

-10

*significantly different from placebo, p = 0.02

 FAM-2 study:
Well being questionnaire

9
8
7 Depression
6 Anxiety
5 Vitality
4
3
2
Placebo Placebo Hawthorn Hawthorn
baseline month 4 baseline month 4
 FAM-2 study:
Well being questionnaire
60

50

40 Positive well-being

Total well-being
30

20

10

0
Placebo Placebo Hawthorn Hawthorn
baseline month 4 baseline month 4
Case study: hypertension + drug treatment

Patient First visit Diet

details Nov 02 Supplements/d
Herbs
CM, female ↑ Bp for 2 yrs ↑fruit&veg
55 yrs, 10mg/d ↓seed oils, use
good diet, Ca channel olive oil
but low on blocker
wholegrains Multi (A-Z)
& oily fish low vitality, 1g vit C
PMH fluid 300 mg Mg
Hospitalised retention,
for 'fainting'
1g Omega-3
spells caused cramps, 360 mg Rutin
by Atenolol. restless legs,
On thyroxine, palpitations. Hawthorn ≡ 5 dried
HRT herb/day
 CM: response to hypotensive treatment
140
120
100
80 Diastolic
60 Systolic

40
20
0 Other minor
June Aug Oct Jan
symptoms
2003 2004 resolved
Case study: hypertension no drug treatment

Patient First visit Diet

details Feb 03 Supplements/d
Herbs
SW, ↑ Bp 6 mo, ↑ fruit&veg, oily fish &
male, overwork, wholegrains,
37 yrs, ↓seed oils, use olive oil
poor low vitality,
diet, sore Multi (high potency)
low in throat↑ ↓ 1g vit C & 1g Omega-3
F&V, catarrh, 1g Ca+500mg Mg
whole- cramps,
grains, stiff neck, Hawthorn ≡ 5 dried herb/day
dairy & headache Skullcap, Cramp bark,
oily fish occ. Valerian, Withania, Astragalus,
Ginger
 SW: response to hypotensive treatment
(no drug therapy) - 2003

180
160
140
120
100 Diastolic
80 Systolic
60
40
20
0 Vitality
Feb April August Nov improved,
signed off
 Safety of Hawthorn

♦ Low acute toxicity: LD50: 6 g/kg body weight - similar

to food
♦ No restriction on long-term use
♦ No interaction with modern drugs including digoxin
(new study)
♦ No adverse reactions expected
♦ No contraindications known
♦ No significant adverse events have been reported in
clinical trials
♦ Overdose: not known
♦ Use of machines/driving: no adverse effects
expected.
Hawthorn dosage equivalent weight of
dried herb (fol+flos) used in studies

❧ FAM I pilot study (healthy, mildly

hypertensive subjects)
• 2.5 g per day ≡ 2.5 ml FE/d
❧ FAM 2 study (type 2 diabetic subjects)
• 6 g per day ≡ 6 ml FE/d
• For a herbal prescription 5 ml tid (15 ml/d)
≡ 40% prescription

FE, fluid extract 1:1

 Conclusions
♦ Hawthorn extract (≡ 6 g per day dried herb)
significantly reduced blood pressure after 4 months in
patients with type 2 diabetes
♦ Hawthorn’s other benefits in diabetic subjects
included:-
● lowering plasma triglycerides, increasing plasma HDL and
increasing insulin levels
♦ Hawthorn can be safely taken with other heart drugs,
making it very suitable for use in integrated medicine
♦ Combined nutritional & phyto- therapy can make a
meaningful difference to lowering hypertension within
6 months of treatment with or without modern drugs
 Acknowledgements
University of Reading:
● Dr George Marakis, Dr Rafe Bundy, Jessica Hope
Diabetes Centre, RBH:
● Dr Hugh Simpson, Eleanor Simpson
Royal Berkshire Hospital, Pathology Lab:
● Paul Robinson
Funding for human studies:
● Lamberts Healthcare Ltd & Lichtwer Pharma UK Ltd
● The University of Reading
New Vitality Clinic:
● Leigh Deller-Smith, Caroline Galloway,
Dr Steve Hicks, Dr Alan Lakin, Freda Miller