Cerebral Vascular Disease, Stroke, Cerebral Aneurysm, Vascular Disease – Part B
25th June 2007 by Arrow Durfee Posted in Uncategorized
The following may be predictive for the risk of stroke:
Fibrinogen levels are useful because fibrinogen is converted into fibrin under the influence of thrombin. Fibrinogen is often elevated after acute trauma or illness, inflammation, and as a side effect of birth control pills.
Triglyceride levels have been found to be a predictor of myocardial infarction, and elevated serum triglycerides have been specifically tied to the occurrence of atherothrombotic stroke and transient ischemic attacks.
Homocysteine levels have been shown to be a risk factor for cardiovascular disease, including atherosclerosis, heart attack, and stroke.
C-reactive protein (CRP) is a sensitive marker of inflammation in the body. Inflammation may be a crucial factor in atherosclerosis and is considered to be a strong predictor of myocardial infarction and stroke (Di Napoli et al. 2001; Ridker 2001).
In addition, overall cardiovascular risk should also be assessed with the following laboratory tests:
Total, HDL, and LDL cholesterol levels have been associated with cardiovascular risk for well over 40 years.
A comprehensive health assessment would also include measurements of the body’s hormones, including DHEA, testosterone, estradiol, and progesterone (for women).
It is important to realize that conventional medicine uses blood tests as a diagnostic tool. Standard reference ranges are based on statistics that find the average value for all people taking the test, including both healthy and unhealthy people. The Life Extension Foundation recommends optimal ranges as a standard to measure wellness.
Optimal Test Ranges
Blood Test Normal Reference Range Optimal Levels
Cholesterol Up to 199 mg/dL Between 180-200 mg/dL
LDL Cholesterol Up to 129 m g d /dL Under 100 mg/dL
HDL Cholesterol 35-150 mg/dL 55-150 mg/dL
Triglycerides Up to 199 mg/dL 60-100 mg/dL
Glucose 65-109 mg/dL 70-99 mg/dL
Homocysteine 5-15 micromol e /L Under 7.2 micromol e /L
Fibrinogen 200-460 mg/dL 200-300 mg/dL
DHEA Men: over 80 mcg/dL
Women: over 35 mcg/dL Men: 400-560 mcg/dL
Women: 350-430 mcg/dL
CRP Up to 4.9 mg/L Under 1.3 mg/L
Ideally under 0.5 mg/L
Drug Strategies for Treatment and Possible Rehabilitation
In the 1960s, hypertension was identified as a treatable risk factor for stroke, and the decline in the incidence of and mortality from a stroke started when physicians began implementing aggressive antihypertensive therapies. In the 1970s, aspirin was first demonstrated effective in preventing strokes, although few physicians prescribe aspirin even to this day to reduce the risk of ischemic stroke. Cigarette smoking has been proven conclusively to be a major risk factor for stroke, and smoking cessation produces a significant risk reduction within 2 years.
Researchers now believe there are an immense number of mechanisms at work causing brain cell damage and death following a stroke. Each of these mechanisms represents a potential route for intervention, as well as prevention. Given the multidimensional nature of ischemic brain cell injury, stroke experts predict that no single drug will be able to completely protect the brain during a stroke. More likely, a combination of agents will be necessary for full recovery potential.
Most strokes culminate in a core area of cell death (infarction) in which blood flow is so drastically reduced that the cells usually cannot recover. This threshold seems to occur when cerebral blood flow is 20% of normal or less. Brain cells ultimately die as a result of the actions of calcium-activated proteases (enzymes which digest cell proteins), lipases (enzymes which digest cell membranes), and free radicals formed as a result of the ischemic cascade.
Without neuroprotective agents, nerve and brain cells may be irreversibly damaged within several minutes. This knowledge is leading to unprecedented therapy development. Expanding knowledge regarding the nature of ischemic brain cell injury is leading researchers to focus on the development of calcium antagonists, glutamate antagonists, antioxidants, and other types of neuroprotective agents. The use of the drug Hydergine to treat acute stroke may be the most effective therapy to combine with t-PA to prevent permanent brain damage.
Those who have already suffered neurologic impairment caused by ischemic stroke may also consider the following drugs.
The most potent antioxidant that a hospital pharmacy normally stocks for the treatment of strokes is Hydergine. Insist that the emergency room doctor administer 10 mg of Hydergine sublingually and another 10 mg of Hydergine orally in liquid form. Hydergine is a powerful antioxidant that reduces free-radical damage. Hydergine will increase the amount of oxygen delivered to the brain, enhance the energy metabolism of brain cells, and protect brain cells against both the low- and high-oxygen environments that ischemic stroke victims often encounter (Marc-Vergnes 1974; Saletu et al. 1990).
Hydergine is used in Europe and the rest of the world as a treatment for stroke, but most emergency room physicians in the United States are reluctant to prescribe it because the FDA does not recognize its value in preventing brain cell death. Paralyzed stroke victims consume billions of healthcare dollars every year, and the reason most ischemic stroke victims are permanently paralyzed is that the FDA has stopped patients from being treated with medications to prevent brain cell death. Regrettably, some hospital formularies may not carry Hydergine or its generic equivalent.
Piracetam, a nootropic medication similar to pyroglutamate (an amino acid), would be useful in the treatment of ischemic stroke if it were approved in the United States for acute use. Piracetam appears to protect brain cells from injury and death during a stroke, thereby lessening the potential for permanent neurological damage. The recommended dosage for piracetam is 4800 mg taken orally. Piracetam is not currently available in the United States , but has been successfully used in Europe for 25 years as reported in the Journal of Pharmacopsychiatry (De Reuck et al. 1999). Piracetam may be obtained by prescription through selected compounding pharmacists throughout the United States . Non-FDA approved drugs, available in other countries, can often be legally prescribed in the United States when a licensed physician collaborates with a licensed compounding pharmacist to safely compound a substance for a particular patient (1938 Federal Government Compound Pharmacy Protection Act). Piracetam is also available from several offshore pharmacies.
A Belgian study indicated that piracetam may be very beneficial if administered within 7 hours after the onset of a stroke (De Deyn et al. 1997).
An article in the journal Stroke described a double-blind, placebo-controlled study of piracetam used to improve language recovery in post-stroke aphasia: 24 stroke patients were assigned to receive either placebo or 2400 mg of piracetam twice a day. After 6 weeks, the piracetam group showed improvement in six language functions, compared with only three in the placebo group. The authors concluded that piracetam as an adjunct to speech therapy improves the recovery of several language functions (Kessler et al. 2000).
A review of three studies of piracetam in ischemic stroke, however, did not find sufficient evidence to support routine use. The authors concluded that more clinical trials are needed (Ricci et al. 2000).
Nimodipine is a European drug especially recommended for head trauma victims. Nimodipine (brand name Nimotop) is a calcium channel blocker specific to the central nervous system. It prevents movement of calcium into the cells of blood vessels, thereby relaxing the vessels and increasing the supply of blood and oxygen. It dramatically improves cerebral blood flow. Nimodipine is an FDA-approved drug used to prevent and treat problems caused by a burst blood vessel around the brain, but it has been ignored by most neurologists treating victims of stroke and other age-related neurological diseases.
An article by Pantoni et al. (2000a) described a 26 week, multinational, double-blind, placebo-controlled study of nimodipine in patients with multi-infarct dementia. This study failed to show a significant effect of nimodipine on cognitive, social, or global assessments. However, a lower incidence of cerebrovascular and cardiac events was observed in the nimodipine-treated patients in comparison with the placebo group. A subgroup analysis found that those patients with subcortical vascular dementia performed better on the majority of neuropsychological tests and functional scales in comparison with patients on placebo (Pantoni et al. 2000b).
Studies on the use of nimodipine on thrombotic and ischemic stroke have shown mixed results (Chua et al. 2001). In one study, low-dose nimodipine therapy was shown over high-dose therapy to positively affect systolic and diastolic blood pressure (Ahmed et al. 2000). However, in a second study, higher dose nimodipine was more effective than lower dose therapy (240 versus 120 mg per a day) in reducing cerebrospinal fluid calcium, thereby improving cerebral blood flow (Bereczki et al. 2000).
There is a delayed response to nimodipine therapy. Nimodipine is recommended for at least 21 days in subarachnoid hemorrhage, and its beneficial effects in migraine prophylaxis usually become apparent after 1 or 2 months of therapy. This delayed benefit may be the reason why nimodipine has not been found to be effective in several clinical studies.
Nimodipine is highly recommended as long-term therapy for thrombotic stroke patients because of its well-known effect on increasing cerebral blood flow and because of its tolerance in most individuals. The most common side effect is hypotension. Rapid elimination rates correspond to a half-life of 1-2 hours which necessitates frequent dosing (e.g., every 4 hours). The recommended dose of nimodipine is 30 mg, three times a day.
Aminoguanidine is being studied for use in stroke because of its action as an inducible nitric oxide synthase inhibitor (Fasbender et al. 2000).
Aminoguanidine is one of the most widely used drugs in Europe . It works by preventing crosslinks caused by glycosylation (a chemical reaction between blood sugar and protein). Animal studies have found that aminoguanidine can prevent diabetic atherosclerotic blood vessel aging and molecular crosslinking in cells throughout the body. Aminoguanidine also prevents destructive crosslinking of collagen and elastin fibers in the brain, which is a primary cause of mental degeneration in the elderly.
An article in Brain Research described a study of aminoguanidine in a rat model of middle cerebral artery occlusion. Daily injections of aminoguanidine (100 mg/kg) began 6 hours after the occlusion. Treatment resulted in a slowing of the growth of ischemic lesions. Interestingly, serial measurements of nitric oxide and nitric oxide synthase activity found no difference between the treatment and placebo groups which suggested that the neuroprotective effects of aminoguanidine may be due to mechanisms other than nitric oxide metabolism (Cash et al. 2001).
An earlier study in the journal Brain Research also used aminoguanidine in a rat model of middle cerebral artery occlusion. The authors found that treatment for a longer period of time (more than 2 days) decreased the volume of ischemic injury. The average reduction was 21% at 3 days and 30% at 4 days (Zhang et al. 1998).
An article in the journal Stroke described a study of aminoguanidine used to treat rats with induced cerebral artery occlusion. Aminoguanidine administered 15 minutes after the onset of ischemia resulted in a significant reduction of infarct volume. Protection was also measured when aminoguanidine was administer e d 1 or 2 hours after the onset of ischemia (Cockroft et al. 1996).
Aminoguanidine and piracetam are European drugs that are not approved for general use in the United States by the FDA. They can, however, be purchased from offshore pharmacies for personal use and may be obtained by physician prescription through compounding pharmacists. The Life Extension Foundation maintains a list of offshore pharmacies that ship European drugs to United States citizens. This list is available by calling the Life Extension Foundation at (800) 226-2370.
Since it is difficult for Americans to obtain aminoguanidine, a nutrient called carnosine should be considered. Carnosine has demonstrated potent anti – glycosylation properties and protects brain cells by additional mechanisms. Carnosine is a peptide made from the amino acids beta-alanine and L-histidine. Several researchers have proposed that carnosine may be of benefit in protecting against stroke. Carnosine acts to regulate the metabolism of zinc and copper, which play a major role in the modulation of central nervous system excitability (Horning et al. 2000; Suslina et al. 2000; Trombley et al. 2000).
In a study in Brain Research Bulletin, rats were subjected to 45 minutes of reduced blood flow (ischemia) to the brain. The result was massive injury that caused 67% of the animals to die. In a group pretreated with carnosine, only 30% died in response to the ischemic injury, and a significant protective effect was shown to in cell membranes and cerebral enzyme levels. The scientists that conducted the study concluded that “carnosine protects against oxidative injury and thereby increases the survival of the animals” (Stvolinsky et al. 2000).
Based on extrapolations from this study and previous reports, the risk of acute death from a stroke in someone taking carnosine every day might be reduced by more than 50% and the chances of significant neuronal impairment that could cause paralysis would also be lowered. The volume of published data on carnosine shows multiple benefits, including antioxidant, anti – glycating, aldehyde quenching, and metal chelating actions.
To derive benefit from carnosine, enough must be consumed to saturate the carnosinase enzyme to make free carnosine available to the body. This dose is typically 1000 mg a day.
Nutrients to Aid in Brain Cell Rehabilitation and to Help Prevent New Strokes
Any disruption of blood flow to the brain causes massive free-radical damage that induces much of the reperfusion injury to brain cells characteristic of strokes. When blood flow is interrupted and subsequently restored (reperfused), tissues release iron, providing a catalyst for the formation of free radicals that often permanently damage brain cells. The Life Extension Foundation has spent millions of dollars conducting research that involves developing methods of protecting the brain cells from injury caused by blood flow disruption. The use of antioxidant nutrients, drugs, and hormones, along with specific calcium-channel blockers and cell membrane-stabilizing agents, provides enormous protection to brain cells.
If you know that an ischemic stroke is occurring, antioxidant vitamins and herbs such as ginkgo biloba would be of benefit. Magnesium in an oral dose of 1500 mg is a safe nutrient to relieve an arterial spasm, a common problem in thrombotic strokes. If you take high-potency antioxidant nutrients at least three times a day, your chances of fully recovering from an ischemic stroke may be significantly improved.
For those who have already incurred brain damage caused by ischemic stroke, a wide range of nutrients may be considered to aid in possible neurological recovery via several different mechanisms. The suggested doses of the nutrients listed below are contained in the summary that appears at the end of this protocol.
One of the most powerful aspects of natural supplements is that they have several different mechanisms by which they exert their beneficial effects. The supplements have been arranged in sections based on their primary action. A few supplements, however, are so important that they are in a section by themselves:
CDP-Choline (Citicholine) may reduce injury to the CNS and inhibit free-radical production.
Ginkgo biloba is a powerful antioxidant. It inhibits platelet aggregation, enhances cerebral blood flow, and is well-known for its beneficial effect on memory and cognitive function.
Essential fatty acids, especially docosahexaenoic acid (DHA), are important in neurological repair because the brain is composed almost entirely of fatty acids. They also have very strong anti-inflammatory properties.
Antioxidant therapy is important in stroke recovery to reduce the oxidative damage that occurs following cellular injury. Antioxidants, such as vitamin C, vitamin E, and alpha-lipoic acid, have been found to be beneficial in stroke.
Minerals play in an essential role in neurologic function primarily as neurotransmitters. Calcium, magnesium, potassium, and selenium are important nutrients.
Hormones such as DHEA have a definite influence on metabolism, including neurological function and repair.
Nitric oxide metabolism is the focus of scientific investigation for its effect on cerebral blood flow and blood pressure. Arginine facilitates nitric oxide synthesis.
Vinpocetine enhances cerebral circulation and improves neuronal energy metabolism.
A healthy diet is an essential part of any wellness plan and many studies have confirmed the beneficial effect of fruits and vegetables on cardiovascular risk.
Choline and pantothenic acid (vitamin B5) are used to produce acetylcholine, the major neurotransmitter that transmits nerve impulses between neurons. Choline is also needed for cell membrane integrity and to move fats in and out of cells. Choline is, therefore, essential for proper brain function because the brain is composed of millions of nerve cells and is composed almost entirely of fats.
CDP-choline is a unique form of choline that readily passes through the blood-brain barrier directly into brain tissue. CDP-choline is a rate-limiting intermediate in the biosynthesis of phosphatidylcholine, an important component of the neural cell membrane. CDP-choline (citicholine) may reduce central nervous system ischemic injury by stabilizing cell membranes and reducing free radical generation.
CDP-choline has been found to be of value in studies on animals and humans. It is approved in Europe and Japan for use in stroke, head trauma, and other neurological disorders (D’Orlando et al. 1995).
Animal Studies of CDP-Choline:
CDP-choline alone and in combination with urokinase resulted in a significant decrease in neuronal damage in a study on rats with focal ischemia induced by occlusion of the middle cerebral artery (Shuaib et al. 2000).
CDP-choline was shown to significantly attenuate blood-brain barrier (BBB) dysfunction after transient forebrain ischemia was induced in gerbils. CDP-choline substantially attenuated edema at 3 days and reduced neuronal death after 6-day reperfusion (Rao et al. 1999).
In a study of rats with induced carotid artery embolisms, CDP-choline was shown to reduce the median infarct size from 37% in the control group to 22% at a dose of 250 mg/kg and 11% at a dose of 500 mg/kg. CDP-choline was also studied in combination with recombinant tissue plasminogen activator (rt-PA). The infarct size was 24% with rtPA 5 mg/kg; 11% with rt-PA and 250 mg/kg CDP-choline; and 19% with rt-PA and 500 mg/kg CDP-choline (Andersen et al. 1999).
A study examined the effects of CDP-choline with medial cerebral artery occlusion induced in spontaneous hypertensive rats. CDP-choline significantly improved behavioral dysfunction (Arnowski et al. 1996).
A study of CDP-choline used to treat ischemia induced in rats demonstrated that CDP-choline significantly reduced infarct volume with a trend towards reducing brain edema and mortality (Schabitz et al. 1996).
Human Studies of CDP-Choline
Four studies of intravenously administered CDP-choline have been conducted outside the United States :
A multicenter, double-blind, placebo-controlled study of CDP-choline (1000 mg per a day intravenously for 14 days) was conducted on patients with acute, moderate to severe cerebral infarction: 133 patients received CDP-choline treatment and 139 received placebo. The group treated with CDP-choline showed significant improvements in level of consciousness compared with the placebo-treated group, and CDP-choline was an entirely safe treatment (Tazaki et al. 1988).
A double-blind, placebo-controlled study of CDP-choline (750 mg a day intravenously for 10 days) used within 48 hours of stroke onset showed a significant improvement on a quantified neurological assessment scale rating motor strength, muscular force, sensation, higher cortical function, and ambulation at 90 days. Patients treated with CDP-choline were significantly more likely to be ambulatory compared with placebo-treated patients at 90 days (Goyas et al. 1980).
A second double-blind, placebo-controlled trial of intravenous CDP-choline (250 mg 3 times a day for 10 days) in stroke patients treated within 48 hours of their symptoms found that a significantly higher percentage of patients had a very good to fairly good recovery with CDP-choline versus placebo treatment at 10 days after stroke (Boudouresques et al. 1980).
A small double-blind, placebo-controlled study examined the effects of CDP-choline (1000 mg a day of IV for 30 days) or placebo in 19 patients with acute stroke treated within 48 hours. In comparison to their baseline assessments, 76% of the CDP-choline-treated patients demonstrated im-provement compared with only 31% of the placebo-treated patients (Corso et al. 1982).
Two trials of orally administered CDP-choline have been conducted in the United States :
A randomized, double-blind, multicenter trial of CDP-choline was conducted on 259 stroke patients. Both the 500 mg per a day CDP-choline group and the 2000 mg a day CDP-choline (orally) group had a significant improvement in terms of the percent of patients who had a favorable outcome on the Barthel Index at 90 days. There were no drug-related serious adverse events or deaths in this study. This study suggests that oral CDP-choline can be used safely with minimal side effects in acute stroke treatment. CDP-choline appears to improve functional outcome and reduce neurologic deficit with 500 mg of CDP-choline appearing to be the optimal dose (Clark et al. 1997).
In a follow-up study in the journal Stroke, 394 patients with acute (24 hours) ischemic stroke received either CDP-choline (500 mg orally daily) or placebo for 6 weeks. No difference was found between the placebo and CDP-choline-treated groups. The authors, however, found a significantly higher percentage of patients with mild strokes in the placebo group (34%) than those treated with CDP-choline (22%). The researchers also found a similar discrepancy in the previous study (above) (Clark et al. 1997). Re-analysis of the data found that the 2000-mg dose provided the greatest therapeutic effect (instead of the 500-mg dose.) For this reason, the authors have chosen to use the 2000-mg dose in future trials (Clark et al. 1999).
A key difference was evident between the U.S. and non-U.S. trials. Those conducted in the United States by Clark et al. (1999) used oral doses of CDP-choline (500 and 2000 mg), whereas the non-U.S. trials used IV CDP-choline at various concentrations and dosages (750 mg per a day, 250 mg 3 times per a day, and 1000 mg per a day).
Ginkgo biloba is one of the oldest living species of tree, with individual trees living as long as 1000 years. Ginkgo is most commonly recommended to help with memory loss and Alzheimer’s disease. It is an antioxidant and inhibitor of platelet aggreg r ation, making a powerful combination for circulatory disorders, such as atherosclerosis.
Ginkgo appears not only to protect against free radicals and abnormal blood clotting, but also enhances neuronal metabolic rates that are severely impaired as a result of ischemic insult.
The conclusions of a report of 40 clinical trials stated that “positive results have been reported for ginkgo biloba extracts in the treatment of cerebral insufficiency” (Kleijnen et al. 1992).
Earlier, double-blind, placebo-controlled trials of ginkgo biloba extract involving 55 patients with acute cerebral ischemia showed a significant improvement in cognitive function based on the Matthews scale (Garg et al. 1995).
Ginkgo biloba was used with heart patients in a treadmill test in France . The doctors concluded: “In a comparison of the differences before and after treatment, the areas of ischemia decreased by 38%” after its use (Mouren et al. 1994).
A French study of mice at the Universite de la Mediterranee ( Marseille , France ) in 1998 reported that neuroprotective drugs such as ginkgo biloba extract could prevent ischemia-induced impairment (Pierre et al. 1999).
A Japanese study found that ginkgo biloba increased cerebral blood flow and reduced infarct volume and ischemic brain damage resulting from middle cerebral artery occlusion induced rats (Zhang et al. 2000).
Essential Fatty Acids
Essential fatty acids are important in both stroke prevention and during the repair of brain tissue damaged by stroke. The brain is almost entirely composed of fatty acids. The Framingham study confirmed that the friendly fats have a beneficial effect on stroke prevention. Essential fatty acids include alpha-linolenic acid ( ALA ) found in perilla and flaxseed oils and docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) found in cold-water fish oil. Fish oils reduce inflammation due to their high content of DHA and EPA. Fish oil acts as platelet aggregation inhibitors as well as triglyceride lowering agents.
Alpha-linolenic acid, an omega-3 fatty acid, may be the most efficient fatty acid in the prevention of stroke by helping to prevent abnormal blood clotting (Renaud 2001). Perilla oil and flaxseed oil are rich sources of alpha-linolenic acid.
An article in the journal Vascular Medicine described the Edinburgh Artery Study of over 1100 subjects examined in a random sample survey. Measurements of the fatty acid levels in red cells found that alpha-linolenic acid was significantly lower in those with stroke and lower limb disease (Leng et al. 1999).
These findings were confirmed in another study of 96 men with incidental stroke and 96 matched controls who were enrolled in the Multiple Risk Factor Intervention Trial. Statistical analysis of fatty acid levels found a 28% and 37% decrease in the risk of stroke with alpha-linolenic acid depending on the increase above average levels. Interestingly, an increase in stearic acid (a food additive derived from beef) was associated with a 37% increase in the risk of stroke (Simon et al. 1995).
Docosahexaenoic Acid (from Fish Oil)
Docosahexaenoic acid (DHA) from fish oil has been shown to prevent the development of hypertension in stroke-prone spontaneous hypertensive rats. Measurements also found that dietary DHA resulted in a decrease of arach i a donic acid (a fatty acid from animal meat that increases inflammation), and restored the inferior learning performance observed in the control group (Minami et al. 1997; Kimura 2000).
Another study found that omega-3 oils, such as fish, perilla, and flaxseed oils, prolonged the survival time of stroke-prone spontaneous hypertensive rats by about 10% as compared to the omega-6 safflower oil. They also found that rapeseed (canola) oil shortened the survival time by about 40% (Miyazaki et al. 2000).
An article in JAMA described the Nurses’ Health Study which found that dietary intake of fish and omega-3 polyunsaturated fatty acids were associated with a reduced risk of thrombotic infarction, primarily among women who did not regularly take aspirin (Iso et al. 2001).
An article in the journal Stroke described a study of 552 men in the town of Zutphen , The Netherlands between 1960-1970. Fewer strokes occurred among the 301 men who always reported fish consumption than among the men who changed fish consumption habits or did not consume fish at all during the study. The authors concluded that these results suggest that consumption of at least one portion of fish per week may be associated with a reduced stroke incidence (Keli et al. 1994).
Vitamin C may be useful in stroke because of its antioxidant properties (Grzegorczyk et al. 2001).
Although ascorbic acid does not pass the blood-brain barrier, its oxidized form, dehydroascorbic acid (DHAA), does. A study in the Proceedings of the National Academy of Science compared the effects of ascorbic acid and DHAA used to treat mice after induction of cerebral artery occlusion. Both DHAA and ascorbic acid reduced infarct volume when given before the ischemia, but only DHAA had an effect when administered after the ischemia. DHAA (250 mg/kg or 500 mg/kg) administered 3 hours after the ischemia reduced infarct volume by six- to ninefold, to only 5% with the highest DHAA dose (Huang et al. 2001a).
An article in the journal Stroke described a 20-year study in Japan that examined vitamin C levels and the risk of stroke. High serum vitamin C concentration was associated with reduced stroke, cerebral infarction, and hemorrhagic stroke risk (Yokoyama et al. 2000).
Vitamin E is well-known for its antioxidant, anti-inflammatory, and antiplatelet effects. Vitamin E increases the production of prostaglandin-I2, a platelet aggreg r ation inhibitor and vasodilator. Vitamin E has also been found to increase HDL (the “good” cholesterol).
The Life Extension Foundation recommends the complete spectrum of vitamin E be used including alpha tocopherol, gamma tocopherol, and the tocotrienols. Vitamin E should be used with care (under the advice of a knowledgeable physician) in patients on anticoagulant drugs (Coumadin).
The gamma tocopherol fraction is the most protective antioxidant for patients taking prescription drug nitrates such as nitroglycerine or isosorbide mononitrite or people using the amino acid arginine for its vasodilating effects.
Alpha-lipoic acid is a commercially available supplement with a variety of actions that may be beneficial during acute stroke. These actions include inhibiting platelet and leukocyte activation and adhesion, reducing free-radical generation, and increasing cerebral blood flow.
The effects of alpha-lipoic acid were studied on strokes induced in mice. Alpha-lipoic acid (100 mg/kg subcutaneous injection) or placebo was administered 1.5 hours before transient middle cerebral artery occlusion was induced. Infarct volume was significantly reduced, and neurologic function was significantly improved in the alpha-lipoic acid group as compared to placebo (Clark et al. 2001).
Most of the tissue damage that occurs from a stroke is observed during reperfusion, which is primarily attributed to oxidative injury from the production of oxygen free radicals. During the process, antioxidants such as glutathione and alpha-lipoic acid are depleted. Pretreatment with alpha-lipoic acid in rats subjected to reperfusion following cerebral ischemia dramatically reduced the mortality rate from 78% to 26% during 24 hours of reperfusion (Panigrahi et al. 1996).
Another study examined the neuroprotective effects of alpha-lipoic acid using models of focal cerebral ischemia in mice and rats. Alpha-lipoic acid was able to reduce the infarct area only when it was administered subcutaneously 1-2 hours before the occlusion of the middle cerebral artery (Wolz et al. 1996).
Calcium, magnesium, and potassium are the most abundant minerals in the body. They play an important role in many of the functions of the body.
Calcium is needed for the transmission of signals between neurons. Ionized calcium initiates the formation of blood clots. It stimulates the release of thromboplastin from platelets and is a cofactor in the conversion of prothrombin to thrombin.
An article in the journal Stroke described a study of calculated dietary intakes of calcium, potassium, and magnesium in the Nurses’ Health Study cohort. Women in the highest quintile of calcium intake had an adjusted relative risk of ischemic stroke that was 31% lower compared with those in the lowest quintile; for potassium intake the corresponding relative risk was 28% lower. The authors concluded that low calcium intake (and perhaps low potassium intake) may contribute to increased risk of ischemic stroke in middle-aged American women (Iso et al. 1999).
Magnesium regulates the absorption of calcium and complements its actions. Magnesium is a natural medicine calcium channel blocker which inhibits calcium ions into cells and can reduce stroke risk. Calcium functions to contract muscles, while magnesium relaxes them. Taking too much magnesium will loosen the stools, causing diarrhea. Magnesium also functions to decrease coagulation, while calcium is involved in increasing coagulation. It is important to maintain a proper ratio between calcium and magnesium.
The use of magnesium in acute stroke cases is at present controversial. Several studies report positive effects, while others do not. There are several reasons for this. The time-to-treatment variable is important because the damage from a stroke happens quickly. Studies in rats show that magnesium is extremely effective if used within 2 hours, but the effectiveness rapidly decreases. A 6-hour window of opportunity is recommended (Yang et al. 2000).
An interesting article in the journal Alcohol proposed that intravenous magnesium may be particularly useful in alcohol-induced hemorrhagic strokes , which are preceded by a rapid fall in intracellular free magnesium ions. They also propose that women are more prone to this fall in magnesium due to the hormonal effects on free magnesium. In support of this hypothesis, they state that premenstrual tension headaches and alcohol-induced headaches (e.g., hangovers) can be ameliorated with intravenous injections of magnesium sulfate (Altura et al. 1999; Babu et al. 1999).
A randomized, placebo-controlled, double-blind study examined the effects of magnesium sulfate given intravenously during the first 24 hours following a stroke. Intravenous magnesium was shown to have a significant positive effect (Lampl et al. 2001).
Potassium is also used by the body for conducting impulses between neurons. Potassium works with sodium to maintain muscle tone, blood pressure, and water balance. Studies have shown that a low potassium diet is related to a higher incidence of stroke (Bazzano et al. 2001). In a study reported in Circulation, diets rich in potassium, magnesium, and cereal fiber reduced the risk of stroke, particularly among hypertensive men. The authors concluded that potassium supplements may also be beneficial, but because of potential risks, use of potassium should be carefully monitored (Ascherio et al. 1998).
Selenium is a trace mineral that is involved in the synthesis of glutathione peroxidase, a key detoxification enzyme. A study examined the association between serum selenium concentration and 5-year risk of cardiovascular disease in 1110 men aged 55-74 years in two rural areas of Finland . In the total cohort, all-cause and cardiovascular deaths were associated significantly with serum selenium of less than 45 mcg/L, with an adjusted relative risk of 1.4 and 1.6, respectively. Among men free of stroke at the outset, low serum selenium was associated significantly with stroke mortality, an adjusted relative risk of 3.7 (Virtamo et al. 1985).
Elevated levels of serum homocysteine strongly predict stroke risk. Homocysteine detoxification requires several nutrients, including vitamin B6, vitamin B12 (cobalamin), and folic acid. Although these three vitamins are currently well publicized, other nutritional factors are also involved in detoxifying homocysteine. Methyl donors, such as trimethylglycine (TMG) and SAMe, are also needed.
B Vitamins and Trimethylglycine (TMG)
Currently, several studies are underway to evaluate the effectiveness of lowering homocysteine with vitamins. The Vitamins in Stroke Prevention (VISP) study is evaluating vitamin B6, B12, and folic acid in patients at least 35 years old that had a nondisabling ischemic stroke within 120 days and high plasma homocysteine (Spence et al. 2001).
The Life Extension Foundation recommends that people measure their homocysteine levels. Homocysteine is of particular concern for those at risk of stroke and victims of stroke. Supplementation with vitamin B6, vitamin B12, folic acid, and trimethylglycine are essential for stroke risk reduction in those whose homocysteine levels are above 7.2 (micromol/L) of blood. The methylating effects of TMG produce SAMe which has been shown to ease depression and remyelinate nerve cells. TMG should be taken with the B vitamin cofactors mentioned above for the full effects to be reached. See the Cardiovascular Disease protocol for more information.
S-adenosyl-L-methionine (SAMe) is an amino acid made naturally in the body. It has been shown to be a potent antidepressant in several double-blind studies (Bell et al. 1988; Kagan et al. 1990). SAMe is so effective that it has rapidly become one of the best-selling dietary supplements in the United States . Studies found that SAMe increases glutathione levels and decreases free radical activity. SAMe also inhibits lipid peroxidation. SAMe is a methyl donor that improves brain methylation which may account for its antidepressant properties.
In experiments with rats, SAMe was found to increase cellular energy levels (ATP and cAMP) and suppress the elevation of lactic acid that commonly follows ischemia. The authors concluded that SAMe protected energy failure and accelerated recovery from ischemia and that it is beneficial for treatment of cerebral ischemia in the acute stage (Katayama et al. 1985).
Policosanol is a natural supplement made from sugarcane. The main ingredient is octacosanol, an alcohol found in the waxy film that plants have over their leaves and fruit.
Octacosanol is a “long chain fatty alcohol” (similar to cholesterol which is also an alcohol). Policosanol is a combination of octacosanol and several other long chain fatty alcohols–hence the name “poli”-cosanol. Keeping octosanol together with other naturally occurring fatty alcohols makes it more stable. There is evidence that octosanol also works better when it is combined with other fatty alcohols. Research has shown that policosanol has the following benefits:
Lowers cholesterol. Several studies have compared policosanol with pr a o vastatin, lovastatin, and sim-vastatin. Policosanol was found to be more effective than all three at lowering LDL and total cholesterol, increasing HDL cholesterol, and improving the ratios of LDL to HDL and total cholesterol to HDL (Castano et al. 1999; Crespo et al. 1999; Prat et al. 1999).
Inhibits the oxidation of LDL (Menendez et al. 1999). Oxidized LDL is dangerous. It promotes the destruction of blood vessels by creating a chronic inflammatory response. Oxidized LDL can also provoke metalloproteinase enzymes (Xu et al. 1999). These enzymes promote blood vessel destruction, partly by interfering with HDL’s protective effect. Studies show that rats treated with policosanol have fewer foam cells, reflecting less inflammatory response causing less blood vessel destruction (Noa et al. 1996; Lindstedt et al. 1999).
Reduces the proliferation of cells. Healthy arteries are lined with a smooth layer of cells so that blood can race through with no resistance. One of the features of diseased arteries is that this layer becomes thick and overgrown with cells. As the artery narrows, blood flow slows down or is blocked completely. Policosanol was tested for its ability to stop the proliferation of these cells (Noa et al. 1996). According to the results, policosanol’s ability to stop cell overgrowth “is in agreement with the anti – proliferative effects reported for other lipid-lowering drugs, such as most of the statins” (Negre-Aminou et al. 1996).
Inhibits the formation of clots. Policosanol may work synergistically with aspirin in this respect. In a comparison of aspirin and policosanol, aspirin was better at reducing one type of platelet aggregation (clumping together of blood cells). But policosanol was better at inhibiting another type. Together, policosanol and aspirin worked better than either alone (Arruzazabala et al. 1997; Stusser et al. 1998). A related effect is that significant reductions in the level of thromboxane occur in humans after 2 weeks of policosanol (Carbajal et al. 1998). Thromboxane is a blood vessel-constricting eicosanoid produced by platelets.
Note: Eicosanoids are powerful chemicals created in cells that can do things such as create fever to kill infections; cause blood vessels in lungs to expand so you can breathe; and reduce inflammation. The body could not function without eicosanoids. Problems arise when eicosanoid reactions are disrupted by drugs, disease, poor diet, and other factors that interfere with their natural balance.
Decreases thrombus weight. Policosanol was shown to significantly decrease the thrombus weight in venous thrombosis experimentally induced in rats, with the protective effect persisting up to 4 hours after its oral administration (Carbajal et al. 1994).
Garlic is a well-known herb that is of great benefit in decreasing the risk of arteriosclerosis. It has been shown to decrease total and LDL-cholesterol; increase HDL-cholesterol; reduce serum triglyceride and fibrinogen concentration; lower arterial blood pressure and promote organ perfusion; enhance fibrinolysis; inhibit platelet aggregation; and lower plasma viscosity.
In a prospective, 4-year clinical trial, standardized garlic caused a 9-18% reduction and 3% regression in plaque volume; a decrease in LDL level by 4%; an increase in HDL concentration by 8%; and lowering in blood pressure by 7%. These effects resulted in a reduction of relative cardiovascular risk for infarction and stroke by more than 50% (Siegel et al. 1999).
Low-dose aspirin and certain nutrients can provide partial protection against abnormal blood clots, but if you have high fibrinogen levels, additional measures should be taken to prevent heart attack and stroke. Platelet-aggregation inhibitors reduce the risk of fibrinogen causing an abnormal blood clot. Some effective nonprescription platelet-aggregation inhibitors include low-dose aspirin, green tea, ginkgo biloba, garlic, and vitamin E.
High vitamin A and beta-carotene serum levels have been reported to reduce fibrinogen levels in humans. For example, animals fed a vitamin A-deficient diet have an impaired ability to break down fibrinogen, but when they are injected with vitamin A, they produce tissue plasminogen activators that break down fibrinogen (Kooistra et al. 1991). A study in the October 1997 Diabetes Care Journal indicates that no one antioxidant may be effective and that total antioxidant capacity is important in reducing the risk associated with fibrinogen and cardiovascular disease (Ceriello et al. 1997).
Additionally, both fish and olive oil have been shown to lower fibrinogen in women with elevated fibrinogen levels (Oosthuizen et al. 1994). The minimum daily amount of fish oil required to produce a fibrinogen-lowering effect is 6 grams. In study results reported in the July 1997 issue of the American Journal of Clinical Nutrition, researchers at Louisiana State University (Baton Rouge) indicated, based on two randomized, double-blind, placebo-controlled, parallel studies conducted in human subjects, that increasing the amount of fish oil consumed to 15 grams a day “decreased fibrinogen concentrations” (Hwang et al. 1997).
Elevated homocysteine levels have been shown to block the natural breakdown of fibrinogen by inhibiting the production of tissue plasminogen activators (Midorikawa et al. 2000). Folic acid, trimethylglycine (TMG), and vitamins B12 and B6 significantly reduce elevated homocysteine levels.
The therapeutic benefits of vitamins B6 and B12 were discussed in a 1998 Cardiovascular Reviews and Reports (United States), reinforcing the use of these vitamins as part of an integrated therapy or disease prevention approach. Another study in 1998, based on data from 80 clinical and epidemiological studies that included more than 10,000 patients, suggested that supplementation with B vitamins, in particular with folic acid, is an efficient, safe, and inexpensive means to reduce the elevated homocysteine levels implicated in cardiovascular risk and disease (Refsum et al. 1998).
Since the 1980s, vitamin C has been studied and found beneficial in the reduction of fibrinogen levels. In a report in the journal Atherosclerosis, heart disease patients were given either 1000 or 2000 mg a day of vitamin C to assess its effect on the breakdown of fibrinogen. At 1000 mg a day, there was no detectable change in fibrinolytic activity (fibrinogen breakdown) or cholesterol. At 2000 mg a day of vitamin C, however, there was a 27% decrease in the platelet-aggregation index, a 12% reduction in total cholesterol, and a 45% decrease in fibrinolytic activity (Bordia 1980).
For additional fibrinogen-lowering effect, the proteolytic enzyme bromelain derived from the pineapple plant may also be effective for coagulation inhibition (Lotz-Winter 1990).
For those seeking to lower elevated fibrinogen levels and inhibit coagulation, 2-6 capsules a day of a supplement called Herbal Cardiovascular Formula containing a standardized bromelain concentrate should be considered.
Low-dose niacin was reported effective in reducing plasma fibrinogen in a 1998 American Journal of Cardiology study that “demonstrated that niacin supplementation decreases plasma fibrinogen and low-density lipoprotein cholesterol in subjects with peripheral vascular disease.” The researchers reported further that those changes in fibrinogen levels are highly correlated with changes in low-density lipoprotein cholesterol in subjects taking niacin (Philipp et al. 1998).
While niacin is considered relatively safe, like cholesterol-lowering prescription drugs, it can cause liver toxicity when taken in high doses. Monitoring liver enzymes every 6 months is important when taking more than 1000 mg of niacin a day. Those with hepatitis should avoid niacin to avoid complications.
Restoring Youthful Hormone Levels
Maintaining healthy hormone levels may assist in rehabilitating neurological impairment due to stroke. Hormone levels naturally decline with aging. These declines contribute to numerous degenerative illnesses such as cardiovascular disease, immune impairment, cancer cell proliferation, and memory decline. The Life Extension Foundation has long endorsed hormone supplementation to prevent or reverse the signs of aging in both men and women. Several hormones have demonstrated an ability to facilitate brain cell energy, maintain proper levels of acetylcholine, and protect brain cell membrane function. These hormones help restore youthful synchronization of nerve impulses within the brain. Individuals who are experiencing cognitive decline from the effects of a stroke are advised to have their hormone levels checked and to discuss hormone replacement with their physician.
Pregnenolone and DHEA improve brain cell activity and enhance memory. (Pregnenolone is converted into DHEA in the body.) DHEA is the most plentiful steroid hormone in the human body, but its exact function is unknown. What is known is that its concentration plummets with age: its daily production drops from 30 mg at age 20 to less than 6 mg at age 80. DHEA is naturally synthesized in abundance in young people from pregnenolone in the brain and the adrenal glands. It is known to affect the excitability of neurons in the hippocampus, the part of the brain responsible for memory.
Current findings suggest that DHEA enhances memory by facilitating the induction of neural plasticity, the condition that permits the neurons (nerve cells of the brain) to change in order to record new memories. Studies have shown that DHEA not only improves memory deficits, but also relieves depression in older people and increases perceived physical and psychological well-being. DHEA has been shown to help preserve youthful neurological function. Together, pregnenolone and DHEA help to maintain the brain cells’ ability to store and retrieve information in short-term memory.
A study found that DHEA and 7-oxo-DHEA -acetate , which is formed from DHEA, completely reversed the memory deficit induced by an injection of scopolamine in young mice. Only acetyl- 7-oxo-DHEA -acetate , a precursor to oxo-DHEA was effective, however, in similar tests on older mice (Shi et al. 2000).
An article in the journal Stroke described a study of DHEA-S used to treat rabbits exposed to ischemia induced by temporary occlusion of infrarenal aorta. Treatment with DHEA-S 5 minutes after the ischemia significantly prolonged the duration of ischemia associated with a 50% probability of permanent paraplegia (paralysis of the lower extremities). The beneficial results were still measurable after 4 days. The authors concluded that DHEA-S may have substantial therapeutic benefit for the treatment of ischemic stroke (Lapchak et al. 2000).
DHEA competitively inhibits cortisol. This means as you take DHEA, cortisol lowers. This is often helpful in stroke risk patients who are often under high stress and have high cortisol and low DHEA levels. DHEA is contraindicated in both men and women with certain hormone-related cancers. See the DHEA Replacement protocol for more information.
Pregnenolone has been described as “the most potent memory enhancer yet found,” according to an article in the Proceedings of the National Academy of Sciences (Flood et al. 1995). Pregnenolone is a hormone formed from cholesterol that is a precursor to all adrenal hormones including progesterone, testosterone, androstenedione, ethiocolanone, estrogen, and DHEA.
Researchers have proposed that pregnenolone may play a role in stroke in regulating the balance between excitation and inhibition in the central nervous system. Pregnenolone enhances N-methyl-D-aspartate (NMDA)-gated currents in spinal cord neurons, while inhibiting receptors for the inhibitory amino acids glycine and gamma-aminobutyric acid, as well as non-NMDA glutamate receptors (Wu et al. 1991).
Melatonin is one of the most potent antioxidants known and readily crosses the blood-brain barrier to provide protection against free radicals generated after cellular injury (such as during a stroke). Melatonin has thousands of published research studies showing its benefits for almost every chronic disease, including cardiovascular disease, age-associated immune impairment, Alzheimer’s, and Parkinson’s disease. Melatonin induces drowsiness and is commonly used in insomnia.
Consideration should be given to the use of melatonin as part of an integrated treatment for thrombotic stroke. According to a 1998 report, “Melatonin is one of the most powerful scavengers of free radicals. Because it easily penetrates the blood-brain barrier, this antioxidant may, in the future, be used for the treatment of Alzheimer’s and Parkinson’s diseases, stroke, nitric oxide, neurotoxicity, and hyperbaric oxygen exposure” (Bubenik et al. 1998).
A study conducted at the University of Texas Health Sciences Center (San Antonio, Texas) and reported in the November 1998 Journal of Neuroscience Research indicates that “considering melatonin’s relative lack of toxicity and ability to enter the brain, these results along with previous evidence suggest that melatonin, which is a natural substance, may be useful in combating free radical-induced neuronal injury in acute situations such as strokes” (Tan et al. 1998).
In laboratory experiments funded by the Life Extension Foundation, in which severe brain ischemia is artificially induced, the addition of melatonin to a cocktail of antioxidants, calcium-channel antagonists, and cell membrane-stabilizing agents provided significant protection against brain damage.
As men age past year 40, hormonal changes occur that perceptibly inhibit physical, sexual, and cognitive function. The outward appearance of a typical middle-aged male shows increased abdominal fat and shrinkage of muscle mass, a hallmark effect of hormone imbalance. A loss of feeling of well-being, sometimes manifesting as depression, is a common psychological complication of hormone imbalance (Barrett-Conner et al. 1999; Rabkin et al. 1999; Schweiger et al. 1999; Seidman et al. 1999; Winters 1999).
According to Jonathan Wright, M.D., coauthor of the book Maximize Your Vitality & Potency: For Men Over 40, the following effects have been reported in response to low testosterone levels (Wright et al. 1998):
Loss of ability to concentrate
Moodiness and emotionality
Touchiness and irritability
Reduced intellectual agility
Reduced interest in surroundings
Reduced libido, erectile dysfunction, or both
The above feelings can all be clinical symptoms of depression, and testosterone replacement therapy has been shown to alleviate these conditions.
In a study conducted on healthy older men, short-term testosterone administration was shown to enhance cognitive function. Cherrier et al. (2001) described a randomized, double-blind, placebo-controlled study of 25 healthy volunteers aged 50-80 years. Participants received weekly intramuscular injections of either 100 mg testosterone enanthate or placebo (saline) for 6 weeks. Circulating total testosterone was raised an average of 130% from baseline at week 3 and 116% at week 6 in the treatment group. Estradiol increased an average of 77% at week 3 and 73% at week 6 in the treatment group. The treatment group had significant improvements in cognition for spatial memory (recall of a walking route), spatial ability (block construction), and verbal memory (recall of a short story) compared with baseline and the placebo group (Cherrier et al. 200l).
A study of 144 men with acute ischemic stroke and 47 healthy male controls found that both total and low free testosterone were associated with increased stroke severity and decreased 6-month survival. Low total testosterone resulted in significantly larger infarct size. The authors concluded that these results supported the idea that testosterone affects the pathogenesis of ischemic stroke in men (Jeppesen et al. 1996).
Human Growth Hormone
Human growth hormone (HGH) is produced naturally by the pituitary gland and secreted during sleep hours. HGH steadily declines during aging from a high of 300-450 mg/mL as a young adult to as low as 30 mg/mL in the elderly. A minimum of HGH must be present in the body to maintain a healthy immune system and brain functioning. HGH is present in cerebrospinal fluid and is able to cross the blood-brain barrier to reach receptor sites on the hypothalamus, pituitary, and hippocampus. The hippocampus controls a significant amount of cognitive functioning and memory.
Researchers have found low levels of HGH in several neurological disorders including Alzheimer’s disease, Parkinson’s disease, MS, and stroke. Considerable research has been done on the effects of HGH over the past decade. In studies on middle aged and elderly people, HGH supplementation has increased muscle mass, skin thickness, and bone mass, while decreasing body fat. In patients with senile dementia and Alzheimer’s disease, noticeable improvements have been observed with sustained use. Researchers theorize that HGH increases blood flow to the brain, regenerates neuronal dendrites and axons, and helps to rebuild protein that leads to the formation of RNA and DNA (Shippen et al. 1998).
An article in the journal Neurology described a study of the hormonal patterns in eight stroke patients and five matched healthy volunteers. Nocturnal plasma hormone measurements showed low growth hormone levels and elevated prolactin concentrations. Cortisol levels, however, were normal. The authors concluded: “Suprahypothalmic lesions influence hypothalamus function so as to facilitate prolactin secretion and inhibit growth hormone release” (Culebras et al. 1984).
Vinpocetine is derived from vincamine, the major indole alkaloid from the periwinkle plant. Vinpocetine has been used for many years in Europe to enhance memory and mental function. Vinpocetine improves blood supply to the brain, increases oxygen and glucose use by the brain, increases the vasodilation response to hypoxia (oxygen deficiency), and reduces abnormal coagulation of the blood.
An article in the European Journal of Neurology described a study of 30 patients diagnosed with acute ischemic stroke. The National Institute of Health Stroke Scale was marginally (but significantly) better in the group treated with vinpocetine at 3 months. No significant adverse effects were seen. The authors concluded that a full-scale trial of vinpocetine was feasible and warranted (Fegin et al. 2001).
Vinpocetine, derived from Vinca minor (lesser periwinkle), has been used as a prescription medication in Europe and Asia for over 20 years. Vinpocetine selectively increases blood flow to the brain and reduces neuronal excitotoxicity, resulting in improved stroke recovery and stroke preventive benefit. Vinpocetine has been shown to increase memory and cognition, improve intellectual performance, and enhance coordination. It has been shown to improve vision, hearing, and tinnit u i s (ringing in the ears) as well (Subhan et al. 1985; Balestreri et al. 1987; Hindmarch et al. 1991).
Theanine is an amino acid found in green tea that has a tranquilizing effect on the brain. Theanine increases GABA (gamma-amino butyric acid), an inhibitory neurotransmitter, while caffeine decreases it. Theanine creates a sense of well-being and relaxation without drowsiness.
An article in Neuroscience Letters described a study in which theanine was given to gerbils 30 minutes before an ischemic stroke was induced by bilateral occlusion of the carotid artery. The number of intact neurons in the hippocampus were was assessed 7 days after the ischemic event. Pretreatment with theanine was found to prevent neuronal death in a dose-dependant manner (Kakuda et al. 2000).
Fruits and Vegetables
An article in JAMA evaluated the relationship between fruit and vegetable intake and cardiovascular disease in two prospective cohort studies: the Nurses’ Health Study and the Health Professionals’ Follow-up Study. After controlling for standard cardiovascular risk factors, those with diets containing over five servings of fruit and vegetables per day had 31% risk reduction compared with the group that consumed the least amount. An increment of one serving per day of fruits or vegetables was associated with a 6% lower risk of ischemic stroke. Cruciferous vegetables, green leafy vegetables, citrus fruit including juice, and citrus fruit juice contributed most to the apparent protective effect of total fruits and vegetables. The authors concluded that these data support a protective relationship between consumption of fruit and vegetables (particularly cruciferous and green leafy vegetables and citrus fruit and juice) and ischemic stroke risk (Joshipura et al. 1999; Suter 1999).
Resveratrol (3,4′,5-trihydroxystilbene) is a phyto-estrogen (plant-based estrogen) found in the skins of most grapes. Its neuroprotective effects are attributed to its antioxidant, vasodilating, and antiplatelet aggregating actions. An article in Life Sciences described a study of resveratrol and infarct size. A middle cerebral artery occlusion was induced in rats 15 minutes after pre-treatment with resveratrol. Resveratrol significantly reduced the total infarction volume (Huang et al. 2001b). Supplemental grape seed-skin extract is a good source of resveratrol.
Consulting Your Physician
When over-the-counter supplements such as aspirin, vitamins, herbs, and oils are used as the primary antithrombotic therapy, the risk of undesirable side effects is reduced significantly. Although over-the-counter medications such as aspirin and natural therapies come with a lower risk of hemorrhaging, they should not be substituted for prescription medication if you are at a high risk for thrombosis.
In all circumstances requiring anticoagulation therapy or antithrombotic therapy, your physician should be consulted if you desire to substitute your medication because the risk can be life-threatening and the appropriate therapeutic dosing is crucial. Since medications such as Coumadin and heparin have a very narrow therapeutic range, anyone on these medications should have his or her blood tested frequently for one or more of the following: PT, PTT, INR. Once the effective dose is achieved, blood testing is recommended every 2-4 weeks to monitor the medication blood levels and avoid overdosing which could lead to hemorrhaging. The template bleeding time test should be conducted if over-the-counter drugs or natural supplements that affect the clotting cascade are added to the regimen. Some of these supplements include vitamins C and E, CoQ10, bromelain, ginseng, garlic, ginkgo biloba, curcumin, St. John’s wort, green tea, policosanol, vinpocetine (periwinkle), and fish oils. If you are taking any of these supplements, do not vary your dose of Coumadin without rechecking your PTT (and INR) and template bleeding time.