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Cerebral Vascular Disease
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.
CDP-Choline
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
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
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).
Antioxidants
Vitamin C
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
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. |