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Thrombosis Prevention
Anti-Inflammatories
Curcumin
Curcumin is the Latin name for the common yellow spice known as turmeric.
Curcumin is commonly used for its anti-inflammatory effects. Curcumin
has also been shown to lower cholesterol.
Research has examined the mechanism of the antiplatelet action of curcumin
(turmeric). Curcumin was shown to inhibit platelet aggregation induced
by ephedrine, ADP, platelet-activating factor (PAF), collagen, and arachidonic
acid. Curcumin acted most strongly against aggregation by PAF and arachidonic
acid. The mechanism appeared to be related to curcumin's inhibition of
thromboxane A2 (Shah et al. 1999). Curcumin should be taken with meals
to avoid the possibility of gastric irritation. The daily dose for most
people is 900 mg with 5 mg of bioperine to enhance assimilation.
DHEA
DHEA has been shown to inhibit inflammatory cytokines (Straub et al. 2000).
With reduced inflammation, less platelet aggregation and LDL migration
into the vessel walls occurs. This can lead to less thrombus formation
and atherosclerosis. DHEA also competitively inhibits cortisol, the other
main adrenal steroid (Boudarene et al. 2002). If cortisol levels are high,
DHEA may be depleted leading to immune deficiencies and reduced muscle
mass. High cortisol also worsens responses to stress.
Nettle Leaf (Urtica Dioica)
In Germany, nettle leaf is an herb with a long tradition of use as an
adjuvant remedy in the treatment of arthritis. It has also been used extensively
in the treatment of allergies. Nettle leaf extract has been found to contain
a variety of active compounds, such as cyclooxygenase and lipoxygenase
inhibitors, and substances that affect cytokine secretion (Obertreis et
al. 1996a; 1996b; Teucher et al. 1996).
Cytokines are proteins that carry messages between cells and regulate
immunity and inflammation. Two cytokines, tumor necrosis factor alpha
(TNF-a) and interleukin-one-beta (IL-1b), are examples of pro-inflammatory
cytokines (Pinto et al. 1999). These cytokines have been found to be elevated
in patients with allergies and arthritis. In animal models, it was shown
that inhibition of TNF-a results in decreased inflammation, while inhibition
of IL-1b effectively prevents cartilage destruction (Probert et al. 1995).
Nettle leaf reduces TNF-a levels by potently inhibiting the genetic
transcription factor that activates IL-lb and TNF-a. This pro-inflammatory
transcription factor, nuclear factor kappa beta ( NF-kb), is known to
be elevated in chronic inflammatory diseases and is essential to activation
of TNF-a. Nettle leaf is also thought to work by preventing degradation
of the natural inhibitor of NF-kb in the body (Riehemann et al. 1999).
In vessels, reduction of inflammatory cytokines (such as TNF-a) also reduces
platelet aggregation and the tendencies toward thrombus formation.
Antioxidants
Quercetin and Catechin
Quercetin and catechin (from green tea) are bioflavonoids with strong
antioxidant properties. Quercetin is primarily used for its beneficial
effects on allergies.
An article in the American Journal of Clinical Nutrition found that
catechin and quercetin inhibited collagen-induced platelet adhesion. The
authors proposed that the effects may be due to the ability of catechin
and quercetin to decrease hydrogen peroxide production (Pignatelli et
al. 2000). Quercetin may also inhibit platelet aggregation by its antioxidant
properties (Xie et al. 1996).
Another study examined the inhibition of thrombin-induced platelet aggregation
by a semisynthetic derivative of quercetin. The authors found that quercetin
inhibited platelet aggregation by reducing calcium mobilization and influx
(Liu et al. 1999, 2000).
Green Tea
Green tea has become very popular for the prevention and treatment of
a wide range of diseases. Green tea protects the cardiovascular system
and might prevent cancer.
A study in the journal Thrombosis Research examined the effects of green
tea tannins and epigallocatechin on platelet aggregation. Both substances
inhibited platelet aggregation induced by ADP and collagen in rats. They
also inhibited platelet aggregation induced by ADP, collagen, and epinephrine
in human blood samples (Kang et al. 1999).
In rabbits, Japanese researchers found that green tea inhibited aggregation
of platelets. The researchers noted that epigallocatechin suppressed collagen-induced
platelet aggregation. Epigallocatechin also inhibited platelet aggregation
induced by thrombin and platelet-activating factor (PAF) (Sagesaka-Mitane
et al. 1990).
Tomatoes
Lycopene, found in tomatoes, has been shown to have strong antioxidant
properties. Lycopene may be particularly effective in blocking the oxidation
of LDL cholesterol.
An article in the journal Platelets described a study of fruits and
their effect on human platelet aggregation in vitro. Researchers found
that tomato extract inhibited both ADP- and collagen-induced aggregation
by up to 70%. The antiplatelet components were found to be concentrated
in the yellow fluid around the seeds in tomatoes. Grapefruit, melon, and
strawberry were also found to have antiplatelet activity, but to a lesser
extent (Dutta-Roy et al. 2001).
Grape Juice
Grapes have gained popularity as a result of several studies that found
that consuming 1 cup of red wine daily had beneficial effects on the cardiovascular
system. Grapes contain proanthrocyanadins, which are concentrated in the
seeds and skin and impart the blue color. Studies have shown that the
antioxidant power of grape seed-skin extract is 50 times greater than
vitamin E and 20 times greater than vitamin C.
An article in the journal Circulation described a study that
examined the effects of purple grape juice on platelets. Laboratory tests
(in vitro) found that purple grape juice inhibited platelet aggregation,
increased nitric oxide production, and decreased superoxide formation.
The researchers then conducted a study with 20 healthy subjects who consumed
7 mL/kg daily of purple grape juice for 14 days. Purple grape juice supplementation
inhibited platelet aggregation, increased platelet nitric oxide production,
and decreased superoxide formation. The authors proposed that purple grape
juice may have beneficial effects in cardiovascular disease (Freedman
et al. 2001).
An article in the journal Nutrition described a study in which 10 healthy
subjects drank 5-7.5 mL/kg daily of purple grape juice, grapefruit juice,
or orange juice for 1 week. Drinking purple grape juice reduced platelet
aggregation by 77%. Orange and grapefruit juice had no effect. The authors
proposed that the flavonoids in grape juice may decrease the risk of thrombosis
(Keevil et al. 2000).
Sulfur-Containing Compounds
N-Acetyl-L-Cysteine
The amino acid N-acetyl-L-cysteine (NAC) inhibits platelet aggregation
by several mechanisms, including:
- Increasing the antiplatelet aggregating effects of L-arginine, which
promotes endogenous synthesis of nitric oxide (Anfossi et al. 1999,
2001). Increases in nitric oxide cause arterial vasodilation increasing
blood flow to the heart and brain in coronary artery disease or cerebral
ischemia. However, in doing so, nitric oxide generates the free radical
nitric peroxide, which is best quenched by gamma tocopherol, a fraction
of vitamin E. A recommended protocol for arterial vasodilation includes
the use of gamma tocopherol (200-400 IU) in combination with L-arginine
(1800-3600 mg) 2-4 times daily, and NAC (250 mg) 3 times daily. This
combination may lower blood pressure as well.
- Affecting platelet-derived growth factor, a key player in fibrosis
(Durante et al. 1999; Okuyama et al. 2001).
NAC is an antioxidant that is helpful in breaking up pulmonary and bronchial
mucus. NAC is also a precursor of glutathione.
Onions
Onion juice has been shown to reduce in vitro human platelet aggregation.
To retain their health benefits, onions should be eaten raw or lightly
steamed because high heat deactivates the active ingredients.
The antiplatelet aggregation action of onions is attributed to sulfur
compounds called thiosulfonates. The strongest thiosulfonates are allicin,
propyl propane thiosulfonate, and ethyl ethane thiosulfonate. All three
of these thiosulfonate compounds were shown to be significantly more potent
platelet aggregators than aspirin at nearly equivalent doses (Briggs et
al. 2000).
In a study using 9-week-old rats, the antithrombotic effects of Welsh
onion juice was examined. Two days after treatment (2 g/kg daily), the
raw Welsh onion juice consumption significantly lowered systolic blood
pressure, prolonged bleeding time, and diminished platelet adhesion as
compared to controls. The authors also found that boiled onion juice had
no effect (Chen et al. 2000).
An article in the journal Nutrition described a study in dogs in which
onion juice was administered 20 minutes after the coronary arteries were
mechanically damaged (narrowed). Treatment with onion juice reversed the
induced cyclic flow reduction within 2.5-3 hours in all five of the treated
dogs. The authors concluded that onion juice might help prevent platelet-mediated
cardiovascular disorders, but also noted that the effects might be greater
in dogs than in humans (Briggs et al. 2001).
Exercise
The effects of exercise on fibrinogen levels have been extensively studied.
Several studies demonstrate that regular exercise lowers fibrinogen levels
and reduces the risk of thrombosis (El-Sayed et al. 1999; 2000; Koenig
et al. 2000; Imhof et al. 2001; Verissimo et al. 2001).
Regular exercise is also well known to provide a host of other health
benefits, particularly for the cardiovascular system.
Prevention of blood clots is a complex task involving maintenance of
a fine balance between the process of coagulation and anticoagulation.
Patients on prescription medications (e.g., Coumadin), as well as those
who combine Coumadin with over-the-counter anti-inflammatories or aspirin,
need close monitoring, in particular weekly or biweekly testing of their
prothrombin using the INR and the TBT test. Patients taking supplements
(such as vitamins, herbs, or oils) should also have their thrombotic risk
factors evaluated in the same way. However, close monitoring of coagulation
balance is usually not necessary in people who are otherwise healthy.
Caution: Never
change an anticoagulation medication without physician approval: thrombosis,
bleeding, and sudden death can occur.
SUMMARY
The Life Extension Foundation recommends a comprehensive approach to
preventing thrombosis with a full assessment of cardiovascular health
(including the presence of hypertension and atherosclerosis) and levels
of homocysteine, fibrinogen, and cholesterol. A thrombosis prevention
protocol fits well with an overall approach to wellness including a healthy
diet and regular exercise. Smoking is a well-known risk factor for chronic
disease and should be avoided.
Thrombosis prevention involves several diverse mechanisms. Several laboratory
tests are recommended to assess the cardiovascular system and guide appropriate
treatment, including cholesterol and triglyceride levels, homocysteine,
template bleeding time, fibrinogen, and CRP (see the protocols on Medical
Testing, Cardiovascular Disease,
Stroke, and Diabetes
for specific recommendations).
The following supplements have demonstrated antithrombotic action by
lowering cholesterol, fibrinogen, and homocysteine; suppressing inflammation;
and by inhibiting platelet aggregation.
- Low-dose aspirin is widely recommended to help prevent abnormal platelet
aggregation, thus reducing heart attack and stroke risk. The Life Extension
Foundation recommends Healthprin, which contains 81 mg of enterically
coated aspirin. One tablet daily is recommended for its anticlotting
and anti-inflammatory effects. Some people may require more than 81
mg of aspirin daily, which can be determined by a TBT.
- Garlic inhibits thrombosis by multiple mechanisms. Garlic is available
in supplement form as Kyolic one-per-day caplets that supply 1000 mg
of odorless garlic. One to two caplets daily is suggested. Another form
of garlic is Pure-Gar Caps (900 mg garlic powder) or Pure-Gar with EDTA
(a chelating agent). Two to four of these garlic capsules are recommended
daily.
- Essential fatty acids GLA (from borage oil), DHA and EPA (from fish
oil). The most efficient way of obtaining all three of these antithrombotic
fatty acids is to take 6 capsules a day of a supplement called Super
GLA/DHA.
- Vitamin E is an antioxidant and platelet aggregation inhibitor. The
recommended dose for most people is 400 IU of alpha tocopheryl succinate,
200 mg of gamma tocopherol, and at least 50 mg of tocotrienols. Vitamin
E with gamma tocopherol is essential when taking arginine, nitroglycerin,
iso-sorbide mononitrate, or other nitrate medications.
- Homocysteine can also be lowered by vitamins B6 and B12 and folic
acid. For vitamin B6, 100-750 mg daily is recommended. Folic acid should
only be taken in the dose of 800-2400 mcg with at least 1000 mcg of
vitamin B12 to prevent masking a B12 deficiency. Trimethylglycine also
lowers homocysteine levels (see the Cardiovascular Disease protocol
for more information). TMG tablets contain 500 mg of trimethylglycine.
One to five tablets daily are recommended. TMG Powder is also available.
One scoop contains 500 mg of trimethylglycine. Two to five scoops daily
are recommended.
- Fibrinogen levels may be lowered by taking at least 2000 mg of vitamin
C; 1000 mg of niacin; and 2000 mg of bromelain or by using a fish oil
supplement that provides 5600 mg of EPA and 3200 mg of DHA.
- Curcumin is well known for its anti-inflammatory action. It has also
been shown to inhibit platelet aggregation. One 900-mg capsule with
5 mg of bioperine daily is recommended for healthy people. Curcumin
should be used with caution in patients with biliary tract obstruction
because it stimulates secretion of cholesterol bile acids from the liver
through the bile duct into the intestines. High doses of curcumin on
an empty stomach may contribute to stomach ulcers or gastric irritation.
- DHEA has been shown to suppress certain inflammatory cytokines that
cause elevated levels of CRP. Typical dosing for men and women is 25-50
mg daily. Refer to DHEA Replacement
Therapy protocol for information and precautions.
- Nettle leaf extract reduces inflammatory cyto-kines, which increase
platelet aggregation that can lead to thrombosis. A dose of at least
1000 mg daily is suggested.
- Quercetin is an antiplatelet agent. About 100-500 mg daily of highly
absorbable water-soluble quercetin is suggested.
- Green tea inhibits several factors involved in abnormal platelet
aggregation. Green tea extract is available in 350-mg capsules and in
300-mg decaffeinated capsules for persons who are sensitive to caffeine.
Two to four capsules daily is recommended for healthy people. Higher
amounts may be taken to further reduce thrombotic risk. Green tea is
best taken with meals. Green tea is also available in bulk leaf or in
tea bags for those who want to brew and drink the tea.
- Tomatoes have been shown to inhibit platelet aggregation. Lycopene,
the main constituent of tomatoes, is a powerful antioxidant. Lycopene
is available in supplement form: 10-30 mg a day is suggested.
- Policosanol has been shown to lower cholesterol, inhibit platelet
aggregation, and prevent thrombosis. Policosanol Tabs usually contain
10 mg of policosanol. To achieve optimal cholesterol levels, the normal
dose is usually 10-20 mg taken daily at bedtime. Monitor cholesterol
levels regularly because levels below 150-180 can be dangerous.
PRODUCT AVAILABILITY
Policosanol,
Super Ginkgo
Extract, Vitamin
E, Gamma
E Tocopherol/Tocotrienols, Essential
Fatty Acids (Super
GLA/DHA, perilla
oil, flaxseed
oil), DHEA,
trimethylglycine,
methylcobalamin
(B12), folic
acid, vitamin
B6, vitamin
C, bromelain,
Kyolic Garlic,
Pure-Gar,
Super K,
Healthprin
(low-dose aspirin), quercetin,
curcumin,
green
tea extract, Super
Lycopene, grape
seed-skin extract, and Life
Extension Mix are available by calling (800) 544-4440 or by ordering
online.
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