Natural Supplements 101 Introduction to Herbal Medicines HERB

HERB
Natural Supplements 101
Introduction to Herbal Medicines
Any plant or plant
part that is primarily
used for medicinal
purposes
R.L.Ogletree, Jr., Pharm.D.
Herbal vs. Homeopathy
Use a plant or part
of a plant which can
elicit desired
response.
Use enough of the
plant or extract to
get that response.
Use a compound
which can cause the
undesired condition.
Use very small
doses.
For a greater
response - use less.
Prevalence
80% of the world’s
population use
plants as their
primary
i
source off
medicines
52% of 200 patients
surveyed have used
supplements in last
year. JABFP 7-8 1996
Projected Market
Natural product market in US
$2.85 billion in 1994
$6.5 billion in 1998
Approx $10 billion in 2001
Approx $23 billion in 2007
Dietary Supplement Health
and Education Act of 1994
Sold as dietary
y supplements
pp
Can make “structure or function”
claims on label
Can not make health or therapeutic
claims on label
Poorly Regulated Market
RX and OTC drugs must be proven safe
and effective
Herbal products labeled as “Dietary
Dietary
Supplements,”
Dietary Supplement and Health
Education Act of 1994
DSHEA (continued)
Can have accompanying literature if a
“balanced view” is presented
Burden of proof for safety (or lack of) is
on the FDA
Disclaimer
Considerations
HERBAL LABELING
These statements have not been evaluated
by the FDA. This product is not intended
to diagnose, treat, cure, or prevent a
disease, but rather is a dietary supplement
intended solely for nutritional support.
Sold and recommended by lay public
Many preparations not standardized
Some complement standard therapy,
nott replace
l
it
Some treat conditions which have
limited drug options
Professional literature of Europe and
Asia abounds with efficacy and safety
studies
German Commission E
Established in 1978
to review and
approve herbal
t t
treatments
t
Looks at:
Safety
Historical data
Efficacy studies
Natural = Safe?
Some potentially dangerous
herbs
Ma Haung
ephedrine
often in combination with caffiene
Bitter Orange
synephrine
phenylephrine
More potentially dangerous
herbs:
Comfrey
used topically on wounds and internally
for g
gastric ulcers
contains unsaturated pyrrolizodine
alkaloids - hepatotoxic
Alfalfa
used a a diuretic and antiasthmatic
can exacerbate or reactivate SLE
More potentially dangerous
herbs:
5-HTP (5-hydroxytryptophan)
precursor to serotonin (5-HT,
5-hydroxytryptamine)
y
y yp
)
used for depression, weight loss, insomnia
orphan drug for postanoxic myoclonus
(along with carbidopa)
GI distress
heart valve problems?
Therapeutically useful herbs
and
d plant
l t components
t
Procyanidolic Oligomers
Procyanidolic Oligomers
Antioxidant
Also called pycnogenols, PCO’s OPC’s
Used by Jacques Cartier 1534-35
Major sources:
Grape seeds
Pine bark
Highly bioavailable
PCO’s continued
Mast cell stablization
Anti-inflammatory activities
antioxidant
cyclo-oxygenase inhibition
Inhibits XO
scavenges hydroxyl radicals (initiation step
of LPO)
scavenges peroxyl radicals(propagation step)
Strengthen vascular system
antioxidant
collagen cross-links
inhibits proteolytic enzymes
Procyanidolic Oligomers Applications
Diabetics
Smokers
Vascular problems
Chronic pancreatitis
Sun worshippers
Heavy drinkers
Exercisers
Allergy
Arthritis
PCO’s - Other Possible
Applications - Theoretical
PCO’s/Studies
Decreased capillary resistance in hypertension/diabetes
controlled,double-blind, 25 patients
150 mg/day PCO’s or placebo for 30 days
Significant improvement in the PCO group
Rheumatoid
Osteo-
Capillary resistance (mm Hg)
20
ADHD
Aminoglycoside therapy
Sem Hop (Paris)
1981;57:1399-1401
PCO’s/Studies - cont’d
8
7.2
Symptom scale
7
6
5
4
3.5
3
1.9
2
1
0
Baseline
45 days
90 days
Veno-lymphatic insufficiency
Phlebologie 1993;46:313
4,729 female subjects on
estrogen/ progestin or
progestin only therapy
showing s/s of venous
insufficiency (esp. feeling of
leg heaviness)
All subject on 150 mg/day
PCO’s
Five symptoms evaluated on a
0 (absent) to 3 (very important)
scale
2.4% adverse events - mostly
GI
18
18
16
15.5
14.7
14.6
14
12
10
Baseline
150 mg/day
30 days
Placebo
PCO’s vision studies
100 normal volunteers recieved 200 mg/day or
placebo for 5 weeks. Sig. improvement of vision in
low light or after glare in PCO group.
J Fr Ophthmol 1988;11:453
1988;11:453-460
460
40 myoptic patients recieved 150 mg/day or placebo
for 30 days. Ann Ott Clin Ocul 1988;114:85-93
85.7% of PCO vs 0% placebo group showed
increase in visual acuity.
40% of PCO vs 0% placebo group showed
improvement in electroretinograpical studies.
PCO dosing
Usually 150 to 300 mg/day in single or
divided doses
Separate from minerals - at least 2 hours
Some say 1 to 1.5 mg/pound for 2
weeks, then cut dose in half
Look for proanthocyanidin content
Echinacea
Also known as purple cone flower
Native to the U.S.
In the NF until the 1950’s
Currently, the most popular herb in U.S.
80-85% for pine bark
90-95% for grape seed
Echinacea Pharmacology
Enhances non-specific immunity
Promotes T-cell activation
Increases natural killer cell activity
Si l
Stimulates
macrophage
h
recriutment
i
Enhances phagocytosis
Stimulates production of IL-1, interferons,
TNF-alpha, and properdin
Inhibits hyaluronidase
Stimulates fibroblast production of hyaluronic
acid
Echinacea Uses
Prevent or treat flu or common cold
Prevent recurrent respiratory and UTIs
Improve
p
immune system
y
suppressed
pp
by
y
chemotherapy or radiation treatment
Topically for superficial wounds
Not recommended for AIDS patients
Not enough known
TNF-alpha
Echinacea Dosage
900 mg/day
Start at the first sign of flu or cold
Continous use should not exceed 8 weeks (a few days
should be plenty)
Use product standardized to at least 4% phenolic
compound
If using a liquid extract, it should cause the tongue to
tingle
Ginger (Zingiber
(Zingiber Officinale
Officinale))
Useful part - the rhizome , sometmes called the root
Primary Use is to prevent nausea and vomiting
Particularly useful to prevent motion sickness
A i ingredient
Active
i
di
- “Pungent
“P
properties”
i ” or
oleoresin
Works at level of the GI tract
Does not cause drowsiness or anticholinergic effects
Echinacea – Drug Interactions
Immunosuppressants – antagonizes
effects (theoretical)
Ginger Root Against
Seasickness*
Randomized, double-blind, placebo
controlled
80 healthy naval cadets on training
p
ship
None especially susceptible to
motion sickness
1 gram powdered ginger root Vs
placebo
scored symptoms of nausea, vertigo,
vomiting and cold sweating
*Acta Otolaryngol 1988;105:45-49
Ginger / Seasickness
60
60
Symptom Score
50
42
Placebo
Ginger
39
40
28
30
p < 0.05
19
18
20
5
10
5
0
Nausea
Vertigo
Vomiting
*
Cold
Sweating
*5 subjects in placebo grp vomited 2 or more times,
but none in the ginger grp vomited more than once
Ginger in Hyperemisis gravidarum - Eur J
Obstet Gynecol Reprod Biol 1991;38:191991;38:19-24
Randomized, double-blind, controlled , crossover
30 patients
250 mg or placebo q.i.d. for four days, then switch to
other group
Decreased vomiting and number of vomiting attacks
in ginger group
70.4% of patients preferred ginger to placebo
Note: Safety of the use of ginger during pregnancy
has not yet been determined
Ginger vs Dimenhydrinate vs Placebo
(Lancet, March 20,1982)
Enrolled 36 undergraduate men and women who reported
very high susceptibility to motion sickness
Randomized to ginger root (940mg), dimenhydrinate
(100mg) or placebo
Placed in rotating chair (4-17rpm)
Vertical component to motion as well
Recorded symptoms every 15s. up to six minutes
Results: mean times P-90s., D-216s., G-335s.
none of P or D gps able to stay in chair 6 minutes
half subjects on ginger stayed full time(p<0.001)
Ginger Dosage
Usually 2 to 4 grams/day
For motion sickness - 1 gram 30 minutes
prior to departure followed by 500 mg
q.i.d. Additional 500 mg at first sign of
nausea
Many recommend a 1 gram daily
maximum during pregnancy
Ginger – Drug Interactions
Black Cohosh
(Cimicifuga racemosa )
Concern with antiplatelet activity?
Uses
alternative to HRT for menopausal symptoms
dysmenorrhea
dyspepsia, rheumatism, sore throat, insect
repellant
Black Cohosh
Chemical Components
triterpene glycosides (actein)
27-deoxyacteine is used in Remifemin
formononetin (an isoflavone)
cinnamic acid esters
Black Cohosh
Mechanism
May bind estrogen receptors; “estriol-like” and
may affect vaginal lining (not associated with
greater risk of breast,
breast ovarian,
ovarian endometrial CA)
“Formononetin” may suppress LH
Contains salicylic acid
Black Cohosh
Safety
FDA: “Herb of undefined safety”
Likely safe if used in low doses;
possibly unsafe when used > 6 months
(G
(German
Commission
C
i i E)
Contraindicated in pregnancy/lactation
GI distress
Rare reports of liver toxicity
Breast cancer aggression?
Black Cohosh
Adverse Effects
GI, visual, decreased BP/HR, perspiration
(1 case report of seizures); increased
vaginal
g
epithelium
p
Insufficient information on salicylate
content
Black Cohosh - Efficacy
Possible effectiveness for menopausal
symptoms, (Menopausal Index, Ham-A)
Hot flushes
Insomnia
Night
h sweats
Also menstrual discomfort
Studies have used the product Remifenin
20 mg bid
Black Cohosh
Drug Interactions
Additive with BP meds?
Estrogenic substances? – not recommended
concomitantly
Insufficient info on salicylate content to
produce interactions
Evening Primrose Oil
High in Gamma-Linolenic Acid
Decreases cholesterol
Has been helpful in arthritis
Has been helpful in PMS
Helpful in atopic dermatitis
Helpful in diabetic neuropathy
Evening Primrose Oil
Daily Dose 4 grams EPO
EPO ~ 9% GLA
Daily Dose 360 mg GLA
Other sources of GLA
Borage Oil ~ 20 - 26% GLA
Black Currant Oil ~ 6 - 19 % GLA
Caution with seizure disorder?
EPO - Diabetic neuropathy
Improvements seen in:
Nerve conduction velocity
Hot and cold thresholds
Sensations
Tendon reflexes
Muscle strength
Pain was not assessed
Keen, et al. Diabetes Care 1993;16(1):8-15
Jamal, et al. Lancet May 10,1986:1098
Boulton, et al. Diabetologia 1997;40 Suppl1:A32 (abstr)
EPO – Drug Interactions
Phenothiazine – precipitate seizures?
Ginseng (Panax
(Panax))
Adaptogen
Ginsenosides
Rb1 and Rg1
increase brain protein synthesis
decrease 5-HT level
increases ACTH
increases ACh release (Rb1)
Ginseng - activities
Anti-stress
Improvement and facilitation of
memory and learning - esp.
esp reactions,
abstract thinking, and mental arithmetic
Modulation of cellular metabolic
processes on CHO, fats, and protein
Promotes hematopoesis
Free radical scavenger
Ginseng
Rg1
increases BP
CNS stimulant
Rb1
decreases BP
CNS depressant
Ginseng - Flu vaccine
Scalgione, et al. Drugs Exp Clin
Res 1996;22:65
227 volunteers
Randomized to Ginseng 200 mg/day or
placebo
After 4 weeks - flu vaccine
Looked at incidence of flu, antibody
titers and natural killer cell activity
Ginseng - Flu vaccine cont’d
Placebo
Ginseng
42
15
50
Ginseng - Flu vaccine cont’d
4 0 0
Placebo
171
Ginseng
272
2 0 0
40
0
30
20
A b tite rs
10
0
In c id e n c e o f F lu
Ginseng in diabetes
Sotaniemi, et al. Diabetes Care
1996;18:1373
36 newly diagnosed Type II diabetics
Randomized to Ginseng 100 mg,
mg 200
mg or placebo for 8 weeks
All were educated for dietary
modifications
Natural killer cell activity nearly
twice as high in ginseng group
Ginseng in diabetes, cont’d
Decreased HbA1C (200 mg group)
Decreased FBG
Improved
mood
well-being (200 mg)
vigor
physical activity (200 mg)
Ginseng in Chronic
Bronchitis
Randomized, open-label, placebocontrolled
75 patients (38 placebo, 37 ginseng)
acute attacks of chronic bronchitis
Augmentin® 875 bid for 9 days
ginseng G-115 100 mg or placebo bid for 9
days
Looking at clearance of bacteria from
lungs daily samples
Scaglione, et al. Clin Drug Invest 2001;21:41-45
Ginseng in Chronic Bronchitis
Results
Bacterial
Counts (% of
baseline)
120
100
Chronic bronchitis - productive cough
on most days at least 3 consecutive
months for at least 2 years
Acute exacerbation - rapid onset of
cough w/purulent sputum & dyspnea,
tachypnea, wheezing, and/or fever
(>38° C)
44 evaluable patients - 31 dropouts
22 missing bacterial counts at least 1 point
9 withdrew
Ginseng in Chronic Bronchitis
Results
Statistically sig. at days 4, 5, 6, and 7
Time to undetectable bacterial count
ABX only
80
ABX only
ABX + Ginseng
60
40
20
0
Baseline Day 4
Ginseng in Chronic Bronchitis
cont’d
Day 5
Day 6
Day 7
Day 8
median - 7 days
mean - 6.7 days
ABX + ginseng
median - 6 days
mean - 5.9 days
Both statistically sig.
Ginseng - Dosing
Use roots from 4 to 6 year old plants
At least 4% ginsenosides
Rb1 to Rg1 ratio of 2:1
Usually 200 to 400 mg/day
Often 2 months on, 1 month off
Siberian ginseng is not the same
Ginkgo biloba
Trees can live up to 1000 years
Very resistant to bacteria, pollution, and
insects
A ginkgo tree survived the Hiroshima
bomb
Most widely used herb in Europe
One of the most widely prescribed
drugs in Germany
Ginseng – Drug Interactions
Diuretics (furosemide) - decreases
diuretic activity
MAOI’s – increases CNS side effects
Insulin sulfonylureas – increases
Insulin,
hypoglycemic effects
Warfarin – increases bleeding risk
CYP3A4 inhibitor
Increased levels of nifedipine
Case report of imatinib (Tykerb)
hepatotoxicity
Ginkgo
Flavone glycosides, terpene lactones
Effects: antioxidant, vascular protectant, inhibit
platelet aggregation, PAF antagonist,
neuroprotectant
Primary uses: Conditions resulting from
decreased cerebral or peripheral circulation (Senile
dementia, vertigo, sudden deafness, intermittent
claudication, vascular impotence)
Also useful: Antioxidant, antiallergy, radiation
induced injury
Ginkgo / Studies
Many good double-blinded studies. Most in German
literature
Meta-analysis of 40 studies found Ginkgo to be useful
in improving such symptoms as difficulty in
concentration or memory, confusion, dizziness, tinnitis,
headaches, depressed mood, etc. Br J Clin Pharmacol
1992;34:352-385
Nine double-blind, randomized clinical trials with
ginkgo in intermittent claudication: increased distance of
pain-free walking by 75-110%, maximum walkling
distance by 52.6-119% and improved blood flow on
doppler ultrasound Am J Nat Med 1995, 2(1):10
Ginkgo - Antidepressant
Induced Sexual Dysfunction
Most had used other drugs to alleviate
(cyproheptadine, yohimbine,
amantadine,, buspirone,
p
, or
antidepressant dose)
Dose: 40 -60 mg bid up to 120 mg bid
Avg. daily dose = 207 mg
Ginkgo - Antidepressant
Induced Sexual Dysfunction
Open-label
63 patients (30 men, 33 women)
Taking antidepressants
Reporting sexual dysfunction
libido (76%)
erectile dysfunction (19%)
delayed or inhibited orgasm (54%)
Cohen, et al. J Sex & Marital Ther. 1998 24:139-143
Ginkgo - Antidepressant
Induced Sexual Dysfunction
Results
84% positive effect
91% women
76% men
n
Helped all 4 phases
desire
excitement (erection, lubrication)
orgasm
resolution (afterglow)
Ginkgo - Dosing
Usual dose 60 - 240 mg/day (usually in
divided doses)
Be sure to use a standardized extract
50:1 concentration
24% flavone glycosides
6% terpene lactones
Side Effects: rare; gastric upset, headaches
Give it time to work
St. John’s wort (Hypericum peforatum)
Named for John the Baptist
Wort - Olde English for plant
Active ingredients:
H
Hypericin
i i
Pseudohypericin
Hyperforin
Inhibits monoamine oxidase
Inhibits reuptake of dopamine, serotonin and
norepinephrine
Effects: antiretroviral, antidepressant
Ginkgo – Drug Interactions
Induces CYP2C19 – lowers levels of
omeprazole, valproic acid, phenytoin
Trazodone – coma
Anti-platelet activity – increases
bleeding risk of warfarin and NSAIDs
St. John’s Wort / Uses
Liscensed in Germany for: Depression,
anxiety, sleep disorders
as effective as standard antidepressants
fewer and milder side effects
Most widely prescribed antidepressant in
Germany
30%-50% of antidepressant Rx’s - around 3
million yearly
St. John’s Wort
(Scientific Evidence)*
Recent review and meta-analysis published
Randomized trials involving 1757 outpatients with
mild to moderate depression: superior to placebo
As effective as amitriptyline
amitriptyline, imipramine
imipramine,
maprotiline
Pooling studies of different preparations of herb
problematic
23 randomized, controlled studies identified between
1983-1994. NONE in the English language!
*BMJ 1996;313:253
St. John’s Wort Drug Interactions
MAO inhibitors
SSRI’s - serotonin syndrome
Triptans – serotonin syndrome (theoretical)
Di
Digoxin
i - lowers
l
di
dig. llevels
l
Indinavir, nevirapine, lamivudine - lowers levels
Cyclosporin, tacrolimus - lowers levels
Simvastatin, atorvastatin – lowers levels
Oral Contraceptives??
St. John’s wort
Dose: Commission E recommends 1 mg hypericin
content daily
Most studies used 2.7 mg hypericin content/day (0.9
mg tid)
Some studies now using 3 - 6% hyperforin
Side effects: GI, photosensitivity?, MAOI?
0 - 25% in studies
one study 3250 patients - 2.4%
2 to 4 weeks may be needed to see results
Fair skinned patients may have problem with UV-A
Saw Palmetto (Serenoa repens)
Also called sabal
Native to the Southeastern U.S.
Liposterolic extract is used
Antiandrogenic,
g
, antiestrogenic,
g
, antiinflammatory
y
Inhibits 5 alpha reductase
Alpha-1 antagonist
Use: benign prostatic hypertrophy
Can decrease prostate size
Can help with symptoms within 1 month
Studies have not shown an effect on PSA
BPH - Meta
Meta--Analyses
Saw Palmetto
18 trials
2939 p
pts
Alpha-1 blockers
25 trials
6840 p
pts
Wilt, et al. JAMA
Djavan, et al. Eur Urol
1998;280:1604
1999;36:1
Saw Palmetto Meta
Meta--Analysis
Mean flow: +2.22 ml/s (28% vs placebo)
Residual volume: -22.05 ml (43% vs
placebo)
BPH - Meta
Meta--Analyses
Saw Palmetto
Urinary tract sx:
28% abs vs placebo
Max flow: + 1.93
ml/s
/ (24%)
(
) abs vs
placebo
ADR’s: 0.8% vs
placebo
Dropouts: 2.1% vs
placebo
Alpha-1 blockers
Urinary tract sx: 10 to
20% abs vs placebo
Max flow: + 5 to 15%
abs vs placebo
ADR’s: 5-10% vs
placebo for terazosin &
doxazosin (5% for
tamsulosin & alfuzosin
Dropouts: 4-10% vs
placebo (Ter & Dox)
Saw Palmetto Dosage
160 mg twice a day
Be sure it is standardized to 85 - 95%
fatty acids and sterols
Well tolerated, but a few GI effects
Licorice
DGL
Glycyrhizin - mimics aldosterone
Uses
liver disorders
chronic fatigue
Precautions
sodium retention
potassium loss
More helpful in ulcers
Increased gastric prostaglandins
Increased mucus secretion
Usually chewable tablets
300 mg - 400 mg 20 min before meals
Deglycyrrhized licorice (DGL) - GI
disorders (activity probably due to
flavonoids)
Milk Thistle (Silybrum
marianum)
Active component - silymarin (a bioflavanoid
complex)
Hepatoprotective:
antioxidant
membrane stabilizer
stimulation of hepatocyte regeneration
Staple in European emergency departments
Uses: alcoholic liver disease, hepatitis (acute, chronic,
infectious, chemical), Amanita mushroom poisoning
Randomized Controlled Trial of Silymarin
in Patients with Cirrhosis of the Liver*
Double- blind, prospective randomized 170 patients
with cirrhosis (91 alcoholic; 79 non-alcoholic)
Silymarin: 140mg TID
Severity:
y Child A:89 B:69 C:12
Mean observation period 41 months
4-year survival rate: 58% silymarin ; 39% placebo
(p=0.036%)
Sub-group analysis: Treatment effective in patients
with alcoholic cirrhosis (p=0.01) and patients rated
Child A (p=0.03)
*J Hepatology 1989;9:105-113
Milk Thistle Dosage
200 mg three times a day
Can change to twice daily after improvement
Be sure p
product is standardized to p
provide
70% silymarin (140 mg in a 200 mg
capsule)
May cause transient loose stools
Valerian
ZZ
Z
Actions:
Enhances activity of GABA
Antagonizes
g
hypnotic
yp
effect of alcohol,, but
not impaired judgement or reaction times
Uses
Insomnia
Anxiety including
traffic stress and performance anxiety
Valerian
(Valeriana officinalis)
Name from Valere - to be in health
Used in WWI for “overwrought
nerves”
”d
during
i artillery
till
bombardment
Over 50 tons sold yearly in France
Active ingredients:
Volatile oil ?
Valepotriates ?
Smells like old socks - Excites cats
Hypnosedatives
Common Treatments of Insomnia
Benzodiazepines
Diphenhydramine
Disadvantages of Hypnosedatives
extended sedation
impaired cognition and motor activity
decreased REM sleep
anticholinergic side effects
dependence
Valerian Dosage
Anxiety: 100 - 200 mg per dose
Insomnia: 200 - 500 mg
Take 30 to 40 minutes prior to bedtime
Dose may need to be increased in
patients used to anxiolytics or
hypnotics
Large doses (>900 mg ) could cause
hangover
Do not abruptly stop benzodiazepines
Coenzyme Q 10
Also known as ubiquinone or
ubidecarenone
Endogenous lipid soluble anti
anti-oxidant
oxidant
Found mostly inside mitochondria
Important as an electron carrier for
respiratory energy transport
Synthesized from mevalonate
NON-BOTANICAL
NONNATURAL PRODUCTS
AND THEIR
IMPACT ON HEALTH
Coenzyme Q 10 Dilated cardiomyopathy
Ma, et al. Blood Press Suppl
19963:53 55
19963:53-55
61 patients
Mitochondrial membrane phospholipid
(MMP) injury
3 groups: placebo, captopril, CoQ10
Coenzyme Q 10 Cardiomyopathy
Coenzyme Q 10 - Dilated
cardiomyopathy, cont’d
At 12 weeks sig. MMP repair in
captopril and CoQ10 groups
2 year survival improvement
placebo:
captopril:
CoQ10:
24.7%
64.0%
72.7%
Coenzyme Q 10 Cardiomyopathy, cont’d
sig improvement in ejection fraction in
84% ((from 44% EF to 60% in 6 months))
85% improved 1 to 2 NYHA classes
Mortality:
12 month
24 month
11.1%
17.8%
Int J Tissue React 1990 12:169
143 patients
chronic stable non-hypertrophic
cardiomyopathy
98% NYHA class III or IV
followed for 6 years
New York Heart Assoc
Classification
I
Well compensated, no physical
limitations no sx at normal activity
II Sl. limitation of p
physical
y
activity,
y, sl.
increase in of sx at normal activity
III Comfortable only at rest. Sx with
less than normal activity
IV Sx at rest
Coenzyme Q 10 in AMI
Randomized, double-blind, placebo
control
144 patients
73 - Co Q 10 120 mg/day X 28 days
71 - placebo X 28 days
Started within 3 days of symptom onset
Singh, et al. Cardiovasc Drugs Ther 1998;12:347-353
Coenzyme Q 10 in
Isolated Systolic Hypertension
Randomized, double-blind, placebo
control
80 patients
32 - Co Q 10 60 mg bid X 12 wks
(additional 9 normotensive)
39 - placebo X 12 wks
SBP 150 -170; DBP<90
Burke, et al. Souther Medical Journal 2001;94(11):1112-1117
Co Q 10 in AMI (cont’d)
CoQ10
Placebo
angina
9.5%
28.1%
arrhythmias
9.5%
25.3%
poor left vent.
f
function
ti
88.2%
2%
22.5%
22 5%
total cardiac
events (fatal &
nonfatal)
15.0%
30.9%
increased Vits. A, E, C, beta-carotene in
tx group
Coenzyme Q 10 in ISH (cont’ed)
10 day washout
SBP > 175 once or > 170 x 3 consec.visits
excluded pt.
pt
Same for DBP > 115
Co Q10 levels baseline and after tx
Coenzyme Q 10 in ISH
results
Coenzyme Q 10 in ISH results
Co Q10 pts
55% responders (> 4 mmHg decrease in
SBP))
(43% > 7 MmHg)
45% non-responders
Avg reduction in
SBP For CO Q10
was 17.8 mmHg(+
7 3)
7.3)
170
165
160
155
Before
After
150
145
Coenzyme Q 10 in peridontal
dz
Patients w/ peridontal dz often have
CoQ10 (around 80% of normal)
The deficiency has been measured in
serum and local tissue
Studies using CoQ10 replacement have
shown improvement in 5 to 7 days
Use with physiotherapy not instead of it
Placebo
135
Co Q10
140
Avg reduction in
responders was
25.9mm Hg (+ 25.9)
Coenzyme Q10 and
Breast Cancer
32 high risk pts. (spread to axillary
nodes)
Co-Q10 (90 mg) and other antioxidants
for 18 months
Lockwood, et al. Molec Aspects Med 1994;15:S231
Coenzyme Q10 and
Breast Cancer Findings
No deaths (4 expected)
No weight loss
I
Improved
d QOL
Reduced analgesic usage
6 partial remission - 2 in full remission
after 24 months (dose increased to 300 390 mg)
Lockwood, et al. Molec Aspects Med 1994;15:S231
Coenzyme Q10 and
Cardiotoxicity
Less left ventricular fractional
shortening in Co-Q 10 group
Decrease in intraventricular septum
wall thickening only in placebo group
Fewer wall motion abnormalities in CoQ 10 group
Iarussi, et al. Molec Aspects Med 1994;15:S207
Coenzyme Q10 and
Cardiotoxicity
Children (3 - 15 y/o) w/acute
lymphoblastic leukemia & NonHodgkins lymphoma
On anthracyclines
10 Co-Q 10; 10 placebo
Cumulative anthracycline doses 210 270 mg/m2
Iarussi, et al. Molec Aspects Med 1994;15:S207
Coenzyme Q 10 - dosing
Breast Cancer - 390 mg/day
CHF at least 200 mg/day
Periodontal dz - 100
“Statin” pts. 100 mg/day
Fat soluble, so fatty form best
Q-gel
peanut butter
Coenzyme Q 10 – Drug Interactions
Warfarin – inconsistent
CoQ10 – vit K like molecule that can
antagonize
g
effects of warfarin
May decrease INR
Chemotherapy – decreases effectiveness
due to antioxidant activity (theoretical)
Chondroitin vs Diclofenac
Morreale, et al. J Rheum 1996;23:1385
Randomized, double-blind
146 patients with knee osteoarthritis
Diclofenac 50 mg t.i.d or chondroitin
400 mg t.i.d.
Diclofenac worked faster, but
chondroitin worked better and lasted
longer and cessation of tx
Glucosamine and Chondroitin
Glycosaminoglycans - components of
cartilage matrix
Chondrotin attracts fluids and nutrients
into proteoglycan molecules
Glucosamine stimulates chondrocyte
activity
Usually used in osteoarthritis
Glucosamine vs Ibuprofen
Vaz. Curr Med Res Opin 1982;8:145
Double-blind
40 outpatients
p
Randomized to Ibuprofen 400 mg t.i.d
or Glucosamine 500 mg t.i.d.
At 2 weeks, ibuprofen was better
At 8 weeks, Glucosamine was better
Side effect: Ibu-25% Gluc-11%
Glucosamine vs Ibuprofen
Qui, et al study
∗Qui, et al. Arzneim-Forsch 1998;48:469
Double-blind
178 outpatients
p
- knee OA
Randomized to Ibuprofen 400 mg t.i.d
or Glucosamine 500 mg t.i.d.
At 2 weeks, and 4 weeks knee pain
scores and knee swelling scores
Qui, et al study
Knee Pain Score
9
8
7
6
5
4
3
2
1
0
Pre-TX
GS
Ibu
4
weeks
Glucosamine vs Ibuprofen
∗Qui, et al. Arzneim-Forsch 1998;48:469
Knee Swelling Score
1.6
Adverse effects due to drugs
1.4
1.2
1
0.8
GS
Ibu
0.6
0.4
0.2
0
Pre-TX
4
weeks
GS - 6%
Ibu - 16%
Drug related drop-outs
GS - 0%
Ibu - 10%
Both statistically significant
Glucosamine 3 Year Study
212 patients
106 glucosamine 1500 mg qd
106 placebo qd
OA of knee
Symptoms - WOMAC scale - every 4
months
Dx progression - X-ray - joint space
width - baseline, 1 yr & 3 yr
Reginster, et al. Arthritis and Rheumatism 1999;9:S400(abstr)
Glucosamine - results
WOMAC scores
Per
Protocol
Glucosamine - results
WOMAC score change
Per
Protocol
ITT
1200
10
1000
5
800
0
Baseline
3 Years
600
400
-5
% change
-10
-15
200
0
Placebo
ITT
-20
Placebo
-25
Placebo
Placebo
Glucosamine - results
Joint Space Width (mm)
Per
Protocol
5.5
5.45
5
45
5.4
5.35
5.3
5.25
5.2
5.15
5.1
5.05
5
4.95
Per
Protocol
ITT
Baseline
3 Years
Placebo
Glucosamine - results
Joint Space Narrowing (mm)
Gluosamine
Glucosamine /Chondroitin
More “antireactive” than antiinflammatory
Chondroprotective
Osteoarthritis is degenerative more
than inflammatory
Glucosamine is more bioavailable than
chondroitin
0.35
03
0.3
0.25
0.2
0.15
0.1
0.05
0
-0.05
-0.1
-0.15
Placebo
ITT
mm change
Placebo
Glucosamine /Chondroitin
Glucosamine 500 mg po t.i.d
Chondroitin 400 mg po t.i.d.
Often available in combo
May want to give NSAIDS for first 2 to
4 weeks
MSM
Glucosamine – Drug Interactions
Theoretical concern that may increase
insulin resistance
May
y require
q
increased dose of insulin or
sulfonylurea – not likely
SAMe
S-adenosylmethionine
Sulfur containing amino acid
Metabolized to homocysteine
Studied in
depression
fibromyalgia
osteoarthritis
cirrhosis
Expensive
Methyl sufonyl methane
Dimethylsulfone
Sulfur containing product
Dehydrating agent
Facilitates attachment of flu viruses to
cells
No published human evidence in
arthritis
SAMe
Osteoarthritis - compared to
piroxicam
naproxen
ibuprofen
indomethacin
Generally - as affective, less side effects
Expensive ~ $150.00/month
SAMe - Meta
Meta--analysis
More effective than placebo
Depression - compared to
SAMe – Drug Interactions
Serotonin syndrome?
amoxapine
maprotaline
trazadone
imipramine
Generally - as affective, less side effects
Expensive ~ $250.00/month
Bressa. Acta Neurol Scand. 1994;Suppl 154:7-14
Chromium
Not an herb - a mineral
Glucose tolerance factor
Increases insulin efficiency
Decreases triglycerides
Increases HDL
Chromium study (China)
180 patients (60 in each group)
Type II diabetics
On other diabetes treatments (insulin,
(insulin
sulfonylureas,metformin, chinese herbs)
Placebo , 200 mcg/day, or 1000
mcg/day divided into 2 doses for 4
months
Anderson, et al. Diabetes. 1997;46(11):1786-91.
Chromium study - results
Chromium study - results
200
H e m o g lo b in A 1 C
10
9
8
7
6
5
9 .1
9 .4
9 .4
177
160
8 .5
7 .5
6 .6
177
129
150
100
Baseline
4 Months
50
B a s e lin e
P la c e b o
4 m o n th s
200 m cg
1000 m cg
Both chromium groups show sig. lower HbA1c at
4 months
Chromium – Drug Interactions
Insulin, sulfonylureas – enhances
hypoglycemic effects
Levothyroxine – lowers levels
Take levothyroxine 30 min before or 4 hrs
after chromium
NSAIDs – increase chromium levels
0
Placebo
1000 mcg
Fasting Blood Glucose
Patient Considerations
Use a reliable source
Interpret extravagant claims in light of
scientific evidence
There could be side effects
Hormonal systems have multiple
feedback mechanisms
Some could interact with other drugs
Very little information about use in
children, pregnant, or lactating women
Recommeded Reference
Sources
Recommended Web Sites
http://www.consumerlab.com
$19.95/yr
☺
☺
Memorial Sloan-Kettering Cancer Center
http://www.mskcc.org/mskcc/html/11570.cfm
☺
☺
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NATURAL
PRODUCTS
Pharmacists Letter/Prescriber’s Letter Guide to
Natural Products, 2002 $100
The Lawrence Review of Natural Products,
(
(monthly
thl update)
d t ) $60/yr
$60/
Facts and Comparison’s Guide to Popular Natural
Products, 2002, $30
Herbs of Choice, 1994 , Tyler,V $25/$13
Physicians & Pharmacists Guide to the Top Ten
Scientifically Proven Natural Products, Ogletree,
RL & Fischer,RG 1997