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Cerebral Vascular Disease
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.
DHEA
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
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
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.
Testosterone
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
- Great timidity
- Feeling weak
- Inner unrest
- Memory failure
- Reduced intellectual agility
- Passive attitudes
- General tiredness
- Reduced interest in surroundings
- Hypochondria
- 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
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
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. |