~Stroke and Cerebrovascular Disease, Part 3

Nutritional Support for Healthy Arteries

Nutritional therapy in cerebrovascular disease associated with atherosclerosis has several interrelated goals. These include reversing endothelial dysfunction with nutrients that stimulate endothelial nitric oxide production, reducing inflammation, enhancing and restoring cerebral blood flow, and providing antioxidant support to reduce the level of damaging free radicals. A number of nutrients have been studied that often accomplish several of these goals.

The following nutrients protect the endothelium:
  • L-arginine. L-arginine is a basic amino acid found in many proteins and is essential to growth and maintenance in all vertebrates. There is evidence that L-arginine plays a major role in maintaining blood vessel dilation and reducing blood pressure, a major risk factor for stroke. L-arginine helps lower blood pressure by serving as a precursor to nitric oxide, which helps keep blood vessels dilated and blood flowing easily (Chionglo BM et al 2006; Boger RH et al 2005).

    In an animal model of stroke, L-arginine was shown to induce an endothelium-dependent increase in cerebral blood flow (Willmot M et al 2005). Among humans, intravenous L-arginine has been shown to alleviate all stroke-like symptoms if administered within 30 minutes of their onset (Koga Y et al 2005). Another study showed that intravenous L-arginine given to patients undergoing carotid endarterectomy surgery was able to reduce the number of embolic signals (restrictions in blood flow) for up to 24 hours after the surgery (Kaposzta Z et al 2001). Although these results are encouraging, oral L-arginine has not been studied in human stroke patients—although human studies have been conducted in heart attack patients and patients with cardiovascular disease.

    While the association between L-arginine and nitric oxide is clear, a few newer studies have suggested that supplemental L-arginine alone may not boost nitric oxide among patients who recently had a heart attack. One study from Johns Hopkins Medical Institutions in Baltimore was stopped after researchers found an increased risk of death in heart attack patients taking L-arginine. There are several possible reasons for this, including the important point that nitric oxide can generate free radicals. By generating production of nitric oxide, L-arginine can raise free radical levels. Life Extension, however, notes that studies questioning L-arginine’s effectiveness failed to provide the necessary antioxidants to counteract any elevation in free radicals caused by the supplement. Thus, Life Extension believes that any person taking L-arginine to lower blood pressure and improve blood flow should also take antioxidants, such as vitamin C and vitamin E.

  • Acetyl-L-carnitine. Acetyl-L-carnitine is a derivative of carnitine. It is involved in the transport of fatty acid across the cell membrane, and it is used as energy in the mitochondria of the cell (Rebouche CJ 2006). It also provides the acetyl component for the synthesis of acetylcholine, an important neurotransmitter. One study has shown evidence that among stroke patients, acetyl-L-carnitine has a beneficial effect on abstract and concrete thinking and memory. The study concluded that acetyl-L-carnitine possesses antioxidant activity that offers protection against lipid peroxidation (Suslina ZA et al 2003). Two other studies reported that large doses of intravenous acetyl-L-carnitine significantly improved cerebral blood flow in patients with chronic cerebrovascular disease who had experienced ischemic stroke (Postiglione A et al 1991, 1990).

  • Propionyl-L-carnitine. Like acetyl-L-carnitine, propionyl-L-carnitine plays an important role is fatty acid oxidation. Research has shown that propionyl-L-carnitine can help protect against endothelial dysfunction. One study in human endothelial cells showed that the carnitine derivatives stimulate the production of nitric oxide in the endothelium, which has an antioxidant, antiproliferative, and anti-inflammatory effect (Calo LA et al 2006). Another study found that propionyl-L-carnitine stimulated nitric oxide’s ability to relax hypertensive arteries in rats (Bueno R et al 2005).
The following nutrients enhance cerebral blood flow, reduce blood pressure, and reduce the size of stroke lesions:
  • Vinpocetine. Vinpocetine has been widely studied for its ability to restore blood flow to the brains of stroke victims. It appears to have multiple effects that interfere with the ischemic cascade. Studies have shown that it reduces the depletion of adenosine triphosphate, which is the main cellular energy source, and functions as an antioxidant (Hadjiev D 2003; Vas A et al 2002). Recently, researchers have found that high-dose, intravenous vinpocetine (at doses up to 70 mg daily) is able to restore blood flow to the brain and reduce the size of ischemic stroke lesions, leading several researchers to identify vinpocetine as a potential therapy for the acute treatment of ischemic stroke (Szilagyi G et al 2005; Szapary L et al 2003; Dezsi L et al 2002). The protective effects are most pronounced in areas of the brain with the highest uptake (Szilagyi G et al 2005). These studies build on previous work showing that oral vinpocetine is also effective in enhancing cerebral blood flow (Dezsi L et al 2002).

  • CDP-choline. CDP-choline is a chemical compound present in a wide array of foods. It plays a life-sustaining role in the normal function of all cells and the structural integrity and signaling capacity of cell membranes, and it moves fats in and out of cells throughout the body (Zeisel SH et al 2006). More than 70 countries, including Japan, use CDP-choline as a prescription drug to treat stroke (Adibhatla RM et al 2005). It appears to have a neuroprotective and reparative effect on cerebral ischemic lesions, reducing the size of lesions during 12 weeks of treatment (Warach S et al 2000). Several additional studies indicate that CDP-choline leads to significant decreases in lesion size and can be used safely in acute stroke treatment (Clark WM et al 1997; Tazaki Y et al 1988). Regrettably, some U.S. studies failed to demonstrate efficacy, and the Food and Drug Administration did not approve it as a drug.

  • Potassium, calcium, and magnesium. Potassium can help lower blood pressure, decreasing risk of cerebrovascular disease and stroke (Sacks FM et al 2001; Suter PM 1999). Evidence has emerged that a balance of potassium, calcium, and magnesium may reduce platelet aggregation and improve insulin resistance. Other studies have shown that combining magnesium and calcium with potassium is more effective than any one of these supplements alone in reducing blood pressure, atherosclerosis, and risk of stroke (Ahsan SK 1998; Sacks FM et al 2001; Broadhurst CL 1997; Ravnskov U 1998; Gillman MW et al 1997; Ascherio A et al 1997; Tavani A et al 1997; Appel LK et al 1997).

  • Vitamin D. There is evidence from clinical trials that vitamin D may play a modest role in blood pressure control and insulin metabolism, both important in slowing the progression of atherosclerosis and reducing risk of stroke (Dakshinamurti K et al 1996; Lind L et al 1995; Boucher BJ 1998). A recent study also showed that deficiencies in vitamin D and flavonoids may predict heart attack and stroke (Marniemi J et al 2005). This new finding is relevant because the NHANES III study, funded by the National Institutes of Health, estimated that 42 percent of African American women between 15 and 49 years of age and 32 percent of white men and women are vitamin D deficient. The overall average increases to 50 percent in the over-fifty population, and vitamin D deficiency is much higher than that in older people, who have decreased capacity to produce vitamin D from exposure to sunlight (Holick MF 2006).

    Omega-3 fatty acids are another important nutrient for stroke victims and those at risk of stroke because of their ability to reduce inflammation. They are found in the oil of cold-water fish and in flaxseed oil. Most people get too much pro-inflammatory omega-6 fatty acids in their diet but not enough omega-3 fatty acids to balance the omega-6. The balance is essential in regulating blood pressure and also in reducing inappropriate platelet aggregation, inflammation, LDL, and other atherosclerosis risk factors (Knapp HR et al 1989; DeBusk RM 2000).

    Randomized clinical trials have found that patients with high omega-3 fatty acid intake experienced decreased incidence of stroke (He K et al 2002; Jeerakathil TJ et al 2001). Omega-3 intake may also slow the progression of atherosclerosis (Kris-Etherton PM et al 2005). One study found that eating coldwater fish as little as once per month reduced risk of ischemic stroke (He K et al 2002). American Stroke Association data indicate that individuals may not get enough omega-3 fatty acids through diet alone; the association suggests that individuals who don’t should consider taking a supplement. Those who have high levels of triglyceride (blood fat) may need larger doses of fish oil supplements (more than 4 g daily) than normally recommended for general prevention purposes (Kris-Etherton PM et al 2005).
The following nutrients are antioxidants:
  • Coenzyme Q10. Coenzyme Q10 (CoQ10) is a powerful antioxidant found in the energy-producing center of the body’s cells. It is involved in making the molecule known as adenosine triphosphate, which is the cell’s major energy source. CoQ10 provides several weapons against atherosclerosis and stroke; it prevents oxidation of LDL, reduces total cholesterol and triglyceride levels, improves insulin sensitivity, decreases glucose levels, and lowers blood pressure, among other things (Ernster L et al 1995; Digiesi V et al 1994, 1990; Langsjoen PH et al 1999; Morisco C et al 1993; Kontush A 1997). The primary food sources of CoQ10 are meat and seafood.

  • Green tea. Green tea catechins, which are rich in flavonoids, possess powerful antioxidant properties that have been studied in the context of limiting damage due to ischemic stroke. Animal studies have shown that green tea extract limits the size of stroke lesions in a dose-dependent manner when administered immediately after an ischemic episode, leading researchers to suggest that green tea may have promise in the acute treatment of ischemic stroke (Suzuki M et al 2004; Lee SY et al 2003). Another study found that animals that had a high intake of green tea experienced less cerebral damage after a stroke than did their counterparts who weren’t consuming green tea (Hong JT et al 2001).

  • Beta-carotene. Beta-carotene is an antioxidant. Large long-term studies have found that daily dietary intake of beta-carotene plays a protective role against atherosclerosis and decreases risk of ischemic stroke (Hak AE et al 2004; Hirvonen T et al 2000). Rich sources of beta-carotene include carrots, squash, green leafy vegetables, milk, lean meat, fish, and poultry.

  • Vitamin C. Vitamin C, also known as ascorbic acid, is a water-soluble antioxidant that protects other compounds from oxidation by being oxidized itself. While it has been shown to lower blood pressure (Duffy SJ et al 1999), other long-term follow-up studies in human beings have found that vitamin C also reduces risk of cardiovascular and heart disease and stroke (Simon JA 1992; Enstrom JE et al 1992; Gale CR et al 1995). A small, well-designed study also found that giving antioxidant vitamins, particularly vitamin C, within 12 hours of an ischemic stroke increased antioxidant capacity, reduced inflammation, and reduced the oxidation of dangerous lipids (Ullegaddi R et al 2005). An earlier, 20-year follow-up study reported that higher vitamin C concentrations reduced incidence of both ischemic and hemorrhagic stroke (Yokoyama T et al 2000). Another study examined the benefit of vitamin C in overweight men with high blood pressure and found that low plasma levels of vitamin C were associated with increased risk of stroke (Kurl S et al 2002).

    Although vitamin C provides cerebrovascular benefits when taken alone (Hirvonen T et al 2000), studies have shown that it may be more powerful when combined with other nutrients, vitamins, minerals, and antioxidants (Galley HF et al 1997; Sacks FM et al 2001; Fotherby MD et al 2000; Toivanen JL 1987; Hajjar IM et al 2001).

  • Vitamin E. Vitamin E is an antioxidant. It regulates oxidation reactions and protects polyunsaturated fatty acids and vitamin A. A large study supplying people with foods that have high levels of vitamin E (plant oils, green leafy vegetables, whole grains, butter, liver, egg yolk, milk, nuts, and seeds) found that higher intake of vitamin E helped reduce risk of death from stroke (Yochum LA et al 2000). Another study reported that eating foods high in antioxidant vitamins C and E helped lower the incidence of stroke, especially notable in smokers (Voko Z et al 2003).

    A study from Helsinki looked at vitamin E supplementation in high-risk individuals with high blood pressure and concluded that although vitamin E supplementation may increase the risk of hemorrhagic stroke, this small risk was outweighed by its protective effect against ischemic stroke (Leppala JM et al 2000). Studies have also shown benefits of vitamin E in improving insulin sensitivity and glucose metabolism, thereby lowering risk of atherosclerosis and stroke (Barbagallo M et al 1999).
Nutrients That Increase Glutathione

Glutathione is the major cellular antioxidant and has a central role in the antioxidant systems that help the body respond to oxidative insults. When glutathione levels are low, oxidative stress is more likely to occur (Thomas JA 2006). Deficiency in glutathione has been associated with atherosclerosis (Morrison JA et al 1999), and evidence indicates that increasing glutathione levels through diet or supplementation may reverse endothelial damage by enhancing nitric oxide production (Prasad A et al 1999). A number of nutrients have been shown to improve glutathione levels:
  • N-acetylcysteine. N-acetylcysteine (NAC) is an antioxidant that helps overcome oxidative stress and enhance glutathione levels (Jiang B et al 1999; Vasdev S et al 1997, 1996; Meister A et al 1986; Lu Q et al 2001). Moreover, NAC lowers homocysteine and lipoprotein that can lead to atherosclerotic changes and helps reverse platelet aggregation that can result in blood clots (Gavish D et al 1991; Wiklund O et al 1996; Bostom AG et al 1996; Hultberg B et al 1997; Horowitz JD 1991).

  • Garlic. Garlic has a long history of medicinal use. It supplies a component of glutathione metabolism, and it is an antioxidant that helps reduce damage from free radicals. Studies have demonstrated that garlic also slightly lowers cholesterol and has antiplatelet effects that help prevent blood clots (Barrett S 2006; Chang HS et al 2005).

  • Selenium. Selenium is a metallic and essential trace element required for glutathione peroxidase. Deficiencies in selenium can produce oxidative stress as well as other stresses that make people vulnerable to infection or disease. It has also been shown to protect against the effects of cerebral ischemia (Ansari MA et al 2004; Schweizer U et al 2004).
DHEA and Stroke

Dihydroepiandrosterone (DHEA) is the most abundant adrenal androgen in the body. It can be converted into both testosterone and estrogen, and many studies have shown that DHEA levels decline as people age. In recent years, researchers have investigated the relationship between DHEA levels and cerebrovascular disease, found compelling evidence that low levels of DHEA are associated with cerebrovascular disease, and even identified DHEA as a possible therapy for the treatment of ischemic stroke.

In one study, researchers hypothesized that DHEA functions as a neuroprotective agent that protects the central nervous system and brain against a variety of insults. After performing the study on rabbits, they found that DHEA, at a daily dose of 50 mg/kg, was able to significantly reduce the damaging effects of ischemia. Perhaps better yet, the protective effect of DHEA was durable, meaning that it lasted more than four days.

Continued . . .

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