HEALTH PROTOCOLS - STROKE by Life Extension

A stroke is the result of loss of blood flow, and subsequent oxygen, to part of the brain. Decreased blood flow to parts of the brain can be caused by blockage ...

HEALTH PROTOCOLS

Stroke

Overview

What is a Stroke?

A stroke is the result of loss of blood flow, and subsequent oxygen, to part of the brain. Decreased blood flow to parts of the brain can be caused by blockage, often from blood clots (ischemic stroke), or by the rupture of a brain blood vessel and subsequent hemorrhaging (hemorrhagic stroke). Strokes are one of the top causes of death and disability.

Ischemic and hemorrhagic strokes are severe and life-threatening. Other less severe types of strokes include transient ischemic attacks (“mini strokes” that resolve within 24 hours) and “silent” strokes that do not cause overt stroke-like symptoms.

Natural interventions such as olive leaf extract and olive oil as well as certain B-vitamins can help reduce the risk of a stroke.

Note: Emergency treatment within 4.5 hours of the onset of a stroke is essential. If you or someone you know exhibit any signs of a stroke, immediately call 911.

What are the Risk Factors for Stroke?

• Age
• Genetic factors
• High blood pressure
• High LDL cholesterol
• Insulin resistance/glucose intolerance
• Sleep apnea
• History of stroke or transient ischemic attack, and others

What are the Signs and Symptoms of a Stroke?

• Sudden numbness or weakness in face or limbs, usually on one side of the body
• Sudden confusion or difficulty speaking or understanding
• Sudden loss of vision
• Sudden severe headache with no apparent cause
• Sudden difficulty walking, dizziness, or loss of balance

Note: If you or someone you know experience stroke-like symptoms call 911 immediately, even if you are unsure whether a stroke occurred.

What are the Conventional Medical Treatments for Stroke?

• Emergency treatments for ischemic stroke:
• Intravenous tissue plasminogen activator (tPA) (ie, an enzyme that leads to clot breakdown)
• Aspirin and antiplatelet agents
• Surgery
• Secondary ischemic stroke prevention may include antiplatelet therapy such as low-dose aspirin or anticoagulant therapy such as warfarin. For patients who cannot take blood thinners, a surgical procedure called left atrial appendage occlusion is another option.
• Emergency treatments for hemorrhagic stroke:
• Surgery to stop the bleeding and drain the blood outside blood vessels
• Vitamin K if the patient was taking warfarin, to counteract its effects
• Nimodipine to control vasospasm and lower blood pressure
• Secondary hemorrhagic stroke prevention may include medications to control blood pressure.

What Natural Interventions Can Help Prevent a Stroke?

Note: Adhering to a Mediterranean-style diet has been associated with reduced all-cause mortality and lower incidence of several age-related diseases, including stroke.

• Olive leaf and olive oil. Olive, an important constituent of the Mediterranean diet, has anti-hypertensive and anti-atherosclerotic effects. A study showed older subjects who consumed olive oil had a 41% lower risk of ischemic stroke than subjects who never consumed olive oil.
• Nattokinase. Nattokinase, an enzyme extracted from fermented soybeans, can help reduce blood pressure in hypertensive patients. Nattokinase reduces the viscosity of blood, lowering blood pressure and clot risk.
• L-carnitine. L-carnitine, a cofactor in the metabolism of lipids, has been shown in preclinical studies to be neuroprotective.
• Vinpocetine. Vinpocetine is a derivative of vincamine, an extract from periwinkle. It has neuroprotective and cerebral blood flow-enhancing properties, as well as anti-inflammatory action.
• Vitamin D. Vitamin D deficiency is an independent risk factor for stroke in certain populations. A study also showed subjects with higher vitamin D levels had the lowest incidence of heart attack and stroke.
• Vitamins B6, B12, and folic acid. Treatment with these B-vitamins can lower stroke risk and overall stroke incidence. A review found that B-vitamin supplementation reduces stroke risk by approximately 12%.
• Omega-3 fatty acids. Omega-3 fatty acids have cerebrovascular protective abilities. In addition to clinical studies demonstrating cardioprotective abilities, a preclinical study found treatment with the omega-3 fatty acid docosahexaenoic acid (DHA) decreased mouse brain damage after an ischemic stroke.
• Dehydroepiandrosterone (DHEA). DHEA improves arterial dilation and protects against endothelial dysfunction. Higher levels of a DHEA metabolite have been associated with less severe strokes.
• Other natural interventions that may reduce the risk of stroke include garlic, vitamin C, flavonoids (eg, resveratrol), and rutin.

Introduction

Stroke is a major killer of Americans, claiming a life every 4 minutes, and is a leading cause of disability (Roger 2012; NSA 2012e). According to a 2012 report from the American Heart Association, about half of stroke survivors 65 or older had some difficulty with movement on one side of their body and over a quarter were institutionalized or in a nursing home 6 months following their stroke (Roger 2012).

A stroke is the result of loss of blood flow, and subsequently oxygen, to part of the brain. Stroke can be caused by either blockage, or rupture and subsequent hemorrhage (bleeding), of a blood vessel in the brain (PubMed Health 2012).

About 54% of stroke deaths happen outside of the hospital. This is partly because many stroke victims do not get to the hospital in time to receive potentially life-saving treatment (Washington State Dept. of Health 2012; Roger 2012).

Receiving emergency treatment within 4.5 hours of stroke onset can mean the difference between life and death (Del Zoppo 2009; Miller 2012). Unfortunately, one study showed that the median time to emergency department admission was 16 hours after onset of stroke symptoms. Only about half of the patients in this study were able to identify one stroke symptom (Zerwic 2007). Knowledge of signs and symptoms of stroke can help victims and their caregivers obtain emergency treatment in a timely manner (NSA 2012e; Roger 2012).

In addition to knowing how to react if stroke symptoms occur, Life Extension emphasizes the need for all aging individuals to take proactive stroke prevention measures. Also, recognition of an epidemic of “silent” strokes is critical. Silent strokes, or mini-strokes, do not cause outright stroke symptoms, but are associated with cognitive dysfunction and increase risk for overt stroke. Estimates indicate that over a quarter of the elderly population has experienced a silent stroke (Saini 2012; Masuda 2001; Lim 2010). Being aware of and taking steps to modify factors that increase stroke risk is paramount in reducing the likelihood of having a stroke or silent stroke (Slark 2012; Lim 2010). In one study, over 40% of possible stroke patients were unable to identify one stroke risk factor (Kothari 1997).

Maintaining optimal blood pressure levels is one of the most important ways to minimize stroke risk. For example, research suggests that people with blood pressure lower than 120/80 mmHg are about half as likely to suffer a stroke as those with higher blood pressure. It has also been reported that each 20/10 mmHg increase over 115/75 mmHg doubles the risk of several vascular complications, including heart attack, heart failure, stroke, and kidney disease (Franco 2004). Similarly, having impaired glucose tolerance nearly doubles stroke risk. Low levels of HDL-cholesterol (“good cholesterol”) and heart rhythm irregularities also significantly increase chances of having a stroke, and people with sleep apnea have twice the risk (Roger 2012).

The good news is that dietary and lifestyle management strategies coupled with natural compounds and certain drugs can target stroke risk factors. Also, comprehensive blood testing can help identify correctable factors involved in stroke and thus help guide prevention strategies.

This protocol will review the different types of stroke and their causes, risk factors, signs, and symptoms. Conventional treatments will be discussed, and strategies to mitigate stroke risk using integrative and scientifically studied natural modalities will be examined. ​

Types of Stroke

There are two main kinds of stroke, ischemic stroke, which makes up about 87% of all strokes, and hemorrhagic stroke (Roger 2012). Transient ischemic attacks (TIAs) and silent strokes are less severe types of stroke, but both can have long-term consequences such as memory impairment (Blum 2012; Wang 2013; NICE 2008; NSA 2009; Das 2008).

Ischemic stroke. An ischemic stroke arises from blockage of blood supply to part of the brain. There are 2 kinds of ischemic stroke: thrombotic and embolic.

• Thrombotic stroke. A thrombotic stroke is caused by a blood clot forming in a blood vessel leading to or in the brain and disrupting blood flow to part of the brain (NSA 2012b).
• Embolic stroke. Embolic stroke occurs when a blood vessel supplying the brain is blocked by circulating debris (ie, an embolus) that originated elsewhere in the body, such as when clots form on artificial heart valves or in the upper chamber of the heart. Embolic strokes are typically caused by blood clots (NSA 2012b).

Hemorrhagic stroke. Strokes caused by blood vessel(s) breaking and leaking blood into the brain are called hemorrhagic strokes. Hemorrhagic strokes account for about 13% of all strokes, but are responsible for more than 30% of all stroke deaths. There are 2 types of hemorrhagic stroke: subarachnoid and intracerebral (NSA 2012b, Roger 2012).

• Intracerebral hemorrhage. Intracerebral hemorrhage is the most common form of hemorrhagic stroke. It occurs when a blood vessel within the brain ruptures and leaks blood into the surrounding tissue. High blood pressure is the primary cause of this type of hemorrhage. Most intracerebral hemorrhages are accompanied by a sudden onset of symptoms, such as loss of consciousness, nausea or vomiting, numbness of the face, or severe headache with no known cause (NSA 2009a).
• Subarachnoid hemorrhage. Subarachnoid hemorrhage is usually caused by an aneurysm, a bulge in a blood vessel wall, bursting in a large artery on or near the delicate membrane surrounding the brain. Blood spills into the area around the brain, which is filled with protective cerebrospinal fluid (CSF). This causes the brain to be surrounded by blood-contaminated CSF. While there are no warning signs for a subarachnoid hemorrhage, symptoms could include a sudden severe headache often described by patients as the "worst headache of my life." At least 30% of subarachnoid hemorrhages lead to a condition called vasospasm, which occurs when blood vessels irritated by excess blood begin to spasm and narrow in size. This makes it difficult to supply the brain with enough blood to survive.

Transient ischemic attack. A transient ischemic attack (TIA), or “mini stroke”, can cause symptoms similar to a stroke, but they usually last only a few hours and are resolved within 24 hours. An example of a symptom shared by both stroke and TIA is visual abnormalities such as sudden vision loss. Since TIAs are short (ie, transient), they do not result in significant permanent brain damage (NICE 2008; NSA 2012d). However, history of TIA increases future stroke risk (Lager 2012,Easton 2009).

Silent stroke. Silent strokes lack overt stroke-like symptoms and commonly go unnoticed (Vermeer 2007). However, silent strokes typically cause lesions in the brain, which can be detected using imaging such as magnetic resonance imaging (MRI). These lesions, known as brain infarcts, are associated with age-dependent memory loss and reduced brain volume (Blum 2012). Studies suggest that silent stroke is a hidden epidemic among American’s, with up to 40% of people over age 70 exhibiting signs (Lim 2010). It is estimated that silent strokes are 5 times more common than symptomatic strokes (Wang 2013).

A silent stroke differs from a transient ischemic attack (TIA) in that TIA symptoms are detectable but usually only last a short time (NICE 2008). Silent strokes can be the result of minor hemorrhages, or they could be lacunar infarcts, in which a penetrating artery becomes occluded, resulting in lesions in the brain's white matter (Yatsu 2004; Norrving 2003). In a study of 2040 stroke-free subjects with an average age of 62, over 10% showed signs of silent stroke when examined by MRI, even though they were not aware of any symptoms (Das 2008).

Warning Signs of Stroke (NSA 2012a): Sudden numbness or weakness of face or limbs, usually on one side of the body Sudden confusion or trouble speaking or understanding Sudden loss of vision Sudden severe headache with no apparent cause Sudden trouble walking, dizziness, or loss of balance and coordination If you experience stroke-like symptoms call 911 without delay, even if it is unclear whether a stroke has occurred.

​

Complications of Stroke

Cognitive abilities, perception, coordination, speech, and balance can be impaired by a stroke. Paralysis is also possible. The specific effects depend on the location and extent of brain damage. For example, since the right hemisphere of the brain controls movement of the left side of the body, a stroke in the right hemisphere can cause paralysis on the left side of the body. A stroke in the cerebellum can cause problems with balance and coordination, and a brainstem stroke can damage involuntary "life-support" functions such as breathing and heart rate and could lead to death. The five most common complications of stroke that render many patients disabled are aphasia, pain, pseudobulbar affect, vascular dementia, and paralysis/spasticity (NSA 2012c,g,f).

• Aphasia. About 25% of all stroke survivors experience aphasia - impairment of the ability to speak and understand spoken or written language. Aphasia is the result of stroke-induced damage to brain regions involved in speech and language processing. Many patients with aphasia benefit from speech/language therapy (NSA 2012g; Mayo Clinic 2012c).
• Pain. Stroke victims may experience pain immediately following a stroke or weeks to months later. Some stroke victims experience local or mechanical pain that may be isolated to joints. This type of pain is caused by damaged muscle or other soft tissue. Other victims may experience a chronic central pain caused by damage to the brain. Central pain occurs because the damaged brain does not interpret pain messages properly, and may register even the slightest touch as painful (NSA 2012f).
• Pseudobulbar affect. A stroke that damages areas in the brainstem and cerebral cortex can cause a condition called pseudobulbar affect, which results in uncontrollable episodes of laughing or crying - often disrupting normal social interaction. Up to 52% of stroke victims report at least some symptoms of pseudobulbar affect (Rosen 2008; Parvizi 2001).
• Vascular Dementia. It is estimated that almost one-fifth of stroke victims will develop problems with their mental and cognitive abilities (NSA 2012c). This loss of intellectual ability is called vascular dementia and results from tissue damage caused by reduced blood flow to the brain. Evidence suggests that stroke doubles the risk of dementia (Sahathevan 2012). Common symptoms of vascular dementia include memory loss, confusion, and decreased attention span (Pendlebury 2009).
• Paralysis & Spasticity. Some stroke victims experience complete paralysis - the inability to voluntarily move muscles. In other cases, patients may experience a tightening or stiffness of muscles that impairs movement of the arms and/or legs. This condition, called spasticity, occurs because messages from parts of the brain to muscles are not properly conveyed (NSA 2010). In some cases, the damaged brain sends signals to muscles to contract for long periods of time, causing painful muscle spasms similar to severe cramping (Bhakta 2000).

Risk Factors for Stroke

Age, gender, race, ethnicity, and genetics have all been identified as non-modifiable risk factors for stroke, with age being the most important (Sacco 1997; Khaw 2006; Francis 2007).

• Age. The stroke rate more than doubles in men and women for each 10 years over age 65.
• Gender. Stroke rates are higher in men than women, but more women die of stroke each year.
• Race & ethnicity. Stroke rates vary extensively among different racial groups. For example, African-Americans are statistically twice as likely to die from strokes as whites. Stroke incidence has risen sharply in Chinese and Japanese populations. Specifically, stroke leads heart disease as a cause of death in Japan.
• Genetics/ hereditary factors. The Framingham Offspring Study demonstrated that family history of stroke is a strong predictor of future stroke risk.

Modifiable stroke risk factors include:

High Blood Pressure

Hypertension, the strongest risk factor for cardiovascular disease worldwide, is associated with about half of ischemic strokes (Kokubo 2012). Also, estimates indicate that 17 to 28% of hemorrhagic strokes among people with high blood pressure could be prevented with blood-pressure lowering treatment (Woo 2004). About 1 in 3 American adults have high blood pressure (AHA 2012b). According to the Cardiovascular Lifetime Risk Pooling Project, men with hypertension throughout middle age have the highest lifetime risk for stroke (Allen 2012).

Blood pressure is measured as systolic and diastolic pressure. Systolic pressure is measured when blood is expelled from the heart as it contracts. Diastolic pressure is measured between contractions. Systolic is the “top” or “first” number, diastolic is the “bottom” or “second”. For most aging individuals, Life Extension recommends an optimal blood pressure target of 115/75 mmHg.

Many clinicians have not adequately addressed the problem of hypertension because of the lax conventional definition of "acceptable" blood pressure. In 2012, it was shown that men and women with consistent blood pressure below 120/80 mmHg had the lowest lifetime risk of stroke and cerebrovascular disease (Allen 2012). It has also been reported that each 20/10 mmHg increase over 115/75 mmHg doubles the risk of several vascular complications, including heart attack, heart failure, stroke, and kidney disease (Franco 2004). Unfortunately, studies have shown that some medical professionals are unlikely to aggressively treat hypertension until blood pressure levels reach 160/90 mmHg (Hyman 2002).

Elevated blood pressure can contribute significantly to endothelial dysfunction> - impairment of normal function of the endothelium, the delicate cellular lining of the inside of blood vessels (Del Turco 2012; Davel 2011). High blood pressure can alter the endothelium and decrease the motility of the arteries and stiffen the arterial wall (Felmeden 2003). When arteries become stiff, they no longer contract and dilate normally, placing stress on the heart (NIH 2011). High blood pressure also contributes to atherosclerosis and blood clot formation. Refer to the Blood Pressure Management Protocol for more information.

Elevated Homocysteine Homocysteine is an amino acid derivative that can damage blood vessels. High homocysteine levels have been associated with an increased risk of stroke recurrence (1.74-fold) and all-cause death (1.75-fold) (Zhang 2010). Homocysteine disrupts endothelial tissue and inhibits the growth of new endothelial cells, which contributes to atherosclerotic plaque formation. Homocysteine can also disrupt the function of brain cells and compromise their survival (Manolescu 2010).

Life Extension recommends an optimal homocysteine level of less than 8 µmol/L. One comprehensive review showed that every 2.5 µmol/L increase above this level is associated with about a 20% increase in stroke risk (Homocysteine Studies Collaboration 2002).

C - reactive protein (hsCRP) C-reactive protein (CRP) is a protein in the blood that correlates with the level of systemic inflammation (Huang 2012b). Elevated CRP measured by a high-sensitivity C-reactive protein blood test is associated with incidence and severity of stroke. C-reactive protein is synthesized by liver cells, and its rate of synthesis is regulated by pro-inflammatory proteins such as interleukin-6 and interleukin-1. While in healthy humans the level of hsCRP is relatively low, it becomes elevated with inflammation, infection, and tissue damage (Casas 2008).

The Cardiovascular Health Study and Emerging Risk Factors Collaboration, both performed a decade ago, found that elevated hsCRP is a risk factor for stroke and can predict stroke outcome. In 2008, the JUPITER trial, which involved 17 802 healthy subjects with hsCRP levels greater than or equal to 2.0 mg/L, found that cholesterol-lowering statin drugs significantly reduced stroke incidence. This may be due in part to an anti-inflammatory effect of statins (Everett 2010; Elkind 2010). In a group of Chinese patients, high levels of C-reactive protein (above 3 mg/L) 15 days before ischemic stroke onset independently predicted death within 3 months (Huang 2012b). Another study involving 467 subjects found that elevated (highest vs. lowest quartile) hsCRP was associated with a more than 4-fold increase in risk of death over 4-years of follow-up after first ischemic stroke (Elkind 2010).

The plasma level of hsCRP is a powerful predictor of endothelial dysfunction, stroke, and vascular death in individuals without known cardiovascular disease. Levels of hsCRP higher than 1.5 mg/L are associated with an increased risk of death after ischemic stroke (Di Napoli 2001). Elevated levels of hsCRP may also be a predictor of secondary cerebrovascular events after an initial stroke (Di Napoli 2005). Life Extension recommends an optimal blood level for hsCRP of less than 0.55 mg/L in men and less than 1.0 mg/L in women.

Excess Fibrinogen

Fibrinogen is a component of blood involved in the clotting/coagulation process. It is converted through enzymatic reactions into the protein fibrin, which binds with other proteins to form a clot. High levels of fibrinogen are associated with cerebrovascular disease, even when other known risk factors such as cholesterol are normal (Kaslow 2011). A study in a Taiwanese population indicated that excess fibrinogen is a major independent predictor of future stroke risk (Chuang 2009). Life Extension recommends an optimal fibrinogen blood level of 295 - 369 mg/dL.

High LDL Cholesterol

Cholesterol, found in all the body's cells, is important for normal cellular function. Cholesterol is carried to and from cells by lipoproteins (high-density lipoprotein [HDL] and low-density lipoprotein [LDL]). LDL (“bad cholesterol”) can contribute to buildup of plaque in arterial walls (AHA 2012d). Studies indicate that high levels of LDL and triglycerides are associated with increased risk of stroke and transient ischemic attack. Statins, drugs that lower LDL cholesterol, reduce stroke risk by as much as 18% and reduce stroke-related deaths by 13% (Rothwell 2011). High levels of HDL (“good cholesterol”) are associated with reduced risk of stroke or cerebrovascular disease (Sacco 2001).

Cholesterol-lowering statin drugs not only reduce the incidence of first stroke, but also reduce chances of having a second, often more debilitating stroke. Statin use is recommended in those who have already experienced a stroke or transient ischemic attack and have an LDL cholesterol level of 100 mg/dL or higher, with the aim of reaching an optimal level of 70 mg/dL (Davis 2012). Life Extension recommends optimal HDL levels over 50-60 mg/dL. Refer to the Cholesterol Management protocol for more information.

Insulin Resistance / Glucose Intolerance

Insulin resistance is a metabolic disorder characterized by reduced sensitivity to the hormone insulin, which regulates blood sugar levels. Insulin signals cells to uptake glucose from the blood. In conditions where insulin levels are low or insulin does not function properly, such as diabetes, blood sugar levels are abnormal. Insulin resistance occurs when insulin levels are normal but its ability to regulate blood sugar is impaired. This results in elevated blood sugar. The insulin-resistant state is associated with hypertension, endothelial dysfunction, abnormal fibrinogen levels, and increased concentrations of LDL particles in the bloodstream (Furie 2008).

In a multiethnic, population-based study of non-diabetic individuals, insulin resistance was associated with a 2.8-fold increased occurrence of a first ischemic stroke (Rundek 2010). This result corroborates previous observational findings that insulin resistance is an independent risk factor for stroke. In the Helsinki Policeman Study, which involved 970 healthy men aged 34 to 64, the rate of stroke incidence was 2-fold higher in diabetes-free patients with higher insulin concentrations (top tertile) compared to those with lower insulin concentrations over a 22-year follow-up (Furie 2008; Pyorala 2000). Refer to the Diabetes protocol for more information.

Sleep Apnea

Many aging individuals suffer from episodic breathing lapses during sleep. This is called sleep apnea. The most common form of sleep apnea occurs when the upper airway collapses (partially or completely) for intermittent periods. This results in characteristic gasping or choking during nighttime breathing (Das 2012).

Sleep apnea deprives its victims of oxygen during sleep. Lack of oxygen due to sleep apnea is associated with inflammation, endothelial dysfunction, and oxidative stress. All of these factors compromise the integrity of blood vessels, increasing the likelihood a stroke-causing blood clot will form. Sleep apnea is independently associated with significantly increased stroke risk, ranging from about 1.5-fold to over 4-fold across several studies, but also may aggravate stroke risk factors such as high blood pressure, atrial fibrillation, and diabetes (Das 2012). One study showed that people with sleep apnea are more likely to die within the first month following stroke than those who breathe normally during sleep (Mansukhani 2011).

Many people with sleep apnea may not know they have it. Participating in a clinical sleep study is the most accurate way to assess sleep quality. Identification and correction of sleep apnea can significantly reduce overall cardiovascular risk (Buchner 2007). ​

Stroke Diagnosis and Treatment

Ischemic stroke damage is time-dependent. Following initial arterial occlusion, cell death cascades to greater areas of the brain until blood flow is reestablished (van der Worp 2007). Hemorrhagic stroke damage is also time-dependent. As blood continues to leak from the original rupture site, the area of the brain damaged by the hematoma increases (Qureshi 2001). It is therefore critical to treat stroke victims as fast as possible to avoid widespread brain damage.

Once a stroke victim has arrived at the hospital, physicians use imaging tests to determine what kind of stroke (ischemic or hemorrhagic) occurred (PubMed Health 2011). Determining the type of stroke is critical because the medications used to treat ischemic stroke will not work for hemorrhagic stroke, and vice versa (Lansberg 2012).

Brain imaging can help detect strokes and determine their nature.

• Computerized tomography angiography (CTA). Computerized tomography angiography is utilized to look for aneurysms, arterial and venous malformations, as well as narrowing of arteries in the neck and brain.
• Computerized tomography (CT). Computerized tomography is a medical imaging tool that can be used to identify cerebral hemorrhaging.
• Magnetic resonance imaging (MRI). Magnetic resonance imaging techniques can aid in the diagnosis of stroke (Schellinger 1999).
• Magnetic resonance angiography (MRA). Magnetic resonance angiography uses a magnetic field, radio waves, and a dye injected into the veins to evaluate arteries in the neck and brain.

Emergency treatment of ischemic stroke. Treatment of ischemic stroke within 4.5 hours of symptom onset is critical. Studies show that rapid dissolution of the blood clot within 4.5 hours of symptom onset can dramatically reduce brain damage (Lansberg 2012). Unfortunately, many ischemic stroke patients do not get to the hospital and receive the appropriate thrombolytic agent until significant brain damage has already occurred (Zerwic 2007).

• Intravenous injection of tissue plasminogen activator (tPA). tPA is FDA-approved to treat acute ischemic stroke (Roth 2011). tPA is an enzyme that converts plasminogen to plasmin - the major enzyme that stimulates clot breakdown. It helps decrease ischemic injury and salvage brain tissue. tPA administration within 4.5 hours of symptom onset is a first choice therapy among patients with no contraindications (Miller 2012; Del Zoppo 2009).Unfortunately, studies indicate that only 2 - 8% of ischemic stroke patients receive this potentially life-saving treatment (Alberts 2012). One study found that 18% of these treatment omissions are avoidable (Cocho 2005). In fact, in many instances, even eligible patients may be denied tPA treatment (Alberts 2012). Sadly, bureaucratic barriers, such as legal liability concerns and insufficient insurance reimbursement, contribute to these deadly denials (Bambauer 2006).Another oft-cited reason for tPA avoidance during acute ischemic stroke treatment is bleeding risk. Physicians often hesitate to treat ischemic stroke victims with tPA if the patient has been taking warfarin for fear of brain hemorrhage. However, evidence suggests that warfarin-treated stroke victims whose INR is less than or equal to 1.7 can be treated with tPA without excess risk of intracranial hemorrhage (Xian 2012).Part of the burden of ensuring timely treatment lies with the patient and/or their caregivers as well. Doctors cannot deliver tPA within the critical 4.5 hour window if a stroke victim arrives at the hospital long after this period has expired. Unfortunately, one study showed that the median time to emergency department admission was 16 hours after onset of stroke symptoms (Zerwic 2007). Calling 911 immediately upon experiencing stroke symptoms is the patient’s and his/her caregivers’ role in ensuring optimal stroke treatment.
• Aspirin & antiplatelet agents. Aspirin is established as an important treatment for ischemic stroke. Studies have shown that 160 or 300 mg doses of aspirin given within 48 hours of ischemic stroke onset can reduce the death rate over time (at hospital discharge or at 6 months ) (van der Worp 2007).
• Surgical procedures. If necessary, emergency procedures must be performed as soon as possible. For example, if a burst aneurysm (a weakness in a blood vessel) causes associated subarachnoid hemorrhage in the brain, a surgeon can clip the aneurysm and stop the bleeding. Another procedure, called balloon angioplasty, can be used to improve blood flow in occluded arteries (Mayo Clinic 2012b).

Secondary ischemic stroke prevention. After stroke, there is a significant risk of a repeat stroke or secondary stroke (Geeganage 2012). To help prevent secondary stroke, patients may be prescribed anti-platelet therapy, including low-dose aspirin or Plavix®, or anticoagulant therapy such as long-term warfarin (Coumadin®) (Alberts 2011; Awada 2011; Bousser 2012).

Emergency treatment of hemorrhagic stroke. Emergency treatment of hemorrhagic stroke focuses on controlling bleeding and reducing pressure in the brain. Surgical procedures are often used to drain the blood that collects outside the blood vessels during a hemorrhage (hematoma) (Dey 2012). If older types of anticoagulant medication (eg, Coumadin®, also known as warfarin) had been taken to prevent blood clots, intervention with vitamin K may be used to counteract the effects of warfarin. Anti-clotting agents (eg, aspirin and tPA) may increase bleeding and cannot be used (Mayo Clinic 2012b).

The medication nimodipine, a calcium channel blocker, is often used to help control vasospasm and may improve outcome among patients with subarachnoid hemorrhage. Nimodipine lowers central blood pressure, and its ability to control vasospasm is thought to be due to inhibition of vasoconstriction (Choi 2012; NSA 2009a; BAF 2011; Kim 2009). An experimental drug called clazosentan, an endothelin receptor antagonist, has been reported in some human and animal studies to reduce the risk of blood vessel spasm and constriction after hemorrhagic stroke and greatly improve chances of survival (Schubert 2008; Sabri 2011; Macdonald 2012). However, other studies have failed to corroborate these findings, so more investigation is needed (Macdonald 2011).

Secondary hemorrhagic stroke prevention. After the acute treatment, medications may be prescribed to control blood pressure, which is a major risk factor for a second stroke (Rashid 2003). Prescription medications for lowering blood pressure include diuretics, calcium channel blockers, beta blockers, ACE inhibitors, and others (AHA 2012a).​

Approaches to Stroke Risk Reduction

Stroke risk reduction hinges upon targeting a variety of known risk factors such as high blood pressure, elevated cholesterol, and insulin resistance, as well as improving dietary and lifestyle habits. However, one of conventional medicine’s most powerful ischemic stroke risk-reduction strategies is to mitigate the likelihood of blood clots using anticoagulants and antiplatelet medications. It is critical to understand that these medications reduce ischemic stroke risk, but increase hemorrhagic stroke risk. Hemorrhagic stroke risk reduction strategies primarily focus on reducing blood pressure, rather than avoiding clotting (Brott 2000; van der Worp 2007; Davis 2012; Bronner 1995; Brisman 2006).

Anticoagulant medications.

Warfarin (Coumadin®), an anticoagulant, has been associated with a 64% reduction in ischemic stroke risk (Lip 2012). Warfarin reduces blood clotting by antagonizing the effects of vitamin K (Siguret 2008). However, warfarin can interact with other drugs, and people taking warfarin require constant monitoring to protect against excessive bleeding.

Recently approved oral anticoagulant drugs are now available to treat blood clots after orthopedic surgeries and may reduce stroke risk is some populations (Boehringer Ingelheim Pharmaceuticals 2012; Mannucci 2011; Ru San 2012). Dabigatran (Pradaxa®), which is a direct thrombin inhibitor, and rivaroxaban (Xarelto™), which inhibits an enzyme involved in coagulation called factor Xa, are examples of anticoagulants that have recently been approved for human use.

These newer therapies may have significant benefits over warfarin, which interferes with vitamin K metabolism. First, they both inhibit clotting factors that do not depend on vitamin K, so they are less sensitive to fluctuations of dietary vitamin K intake. Dabigatran does not exhibit major interactions with foods or other medications (Steffel 2011). Unlike warfarin, people taking these medications do not need regular blood testing to monitor coagulation (Thethi 2011). In clinical trials, both treatments were at least as effective as warfarin for reducing stroke risk in patients with atrial fibrillation, and preventing/treating deep vein thrombosis, with a reduced risk of bleeding (Connolly 2009; Schulman 2009; Eriksson 2008). For more information see the Blood Clot Prevention protocol.

Advantages of Pradaxa® vs. warfarin include:

• Rapid onset of action
• Predictable, consistent anticoagulant effects
• Low potential for drug-drug interaction
• No requirement for anticoagulant blood test monitoring
• Preliminary efficacy and safety advantages vs. warfarin based on initial head-to-head, hard-endpoint data
• No need to maintain low vitamin K levels. Insufficient vitamin K promotes arterial calcification.

Disadvantages of Pradaxa® vs. warfarin include:

• No antidote for reversal of over anti-coagulation effect. When too much warfarin is given and the patient's INR indicates they are at risk for a major bleed (or are pathologically bleeding), vitamin K can be injected to immediately reverse warfarin's anti-coagulant effect. If too much Pradaxa® is taken, there is no immediate antidote.
• No long-term safety data on Pradaxa® (the case with virtually all newly approved drugs)
• More expensive than warfarin

Anti-platelet medications. Platelets are cell fragments in the blood involved in clot formation. Anti-platelet drugs make these cell fragments less sticky and less likely to clot. The most frequently used anti-platelet medication is aspirin. Aggrenox®, combination of low-dose aspirin and the anti-platelet drug dipyridamole, may be prescribed instead (Norrving 2006). Other alternatives include clopidogrel (Plavix®) or ticlopidine (Ticlid®) (Merck Manual 2007; Forbes 1998; Aw 2012; Murray 1994).

Left atrial appendage occlusion. For some patients with atrial fibrillation and who cannot take anti-coagulants or other blood-thinners, a surgical procedure called left atrial appendage occlusion has been shown to inhibit clot formation and decrease stroke risk (Holmes 2009; Lopez-Minguez 2012). The left atrial appendage is a muscular pouch that serves as a reservoir for one of the chambers of the heart (left atrium). In the presence of arrhythmia, blood in the appendage is prone to clotting (Alli 2012). ​

Natural Strategies to Reduce Stroke Risk

Conventional medications and surgeries used to prevent stoke and cerebrovascular disease are often associated with side effects and are limited in their ability to target the multiple factors that contribute to stroke. Life Extension emphasizes a global stroke prevention strategy. This strategy includes a series of preventive measures such as reducing chronic inflammation, maintaining healthy body weight, reducing cholesterol, suppressing homocysteine and fibrinogen levels, and lowering blood pressure (Houston 2010).

Mediterranean Diet. The traditional Mediterranean diet is rich in fruits, vegetables, whole grains, and fish, and low in red meat and sweets (Fung 2009). Adherence to a Mediterranean diet is associated with reduced all-cause mortality and lower incidence of several age-related diseases, including stroke (Mitrou 2007; Fung 2009). A 2011 study found that strict adherence to a Mediterranean diet decreased the likelihood of ischemic stroke irrespective of cholesterol levels, age, and gender (Kastorini 2011). In a separate population study, adherence to a Mediterranean diet significantly decreased the risk of ischemic stroke, heart attack, and vascular death (Gardener 2011). In a study surveying over 70 000 American women, a "prudent" diet of fruits, vegetables, fish and whole grains was associated with a lower risk of total and ischemic stroke compared to a "Western" diet high in processed meats, refined grains, and sweets (Ding 2006). Consuming a Mediterranean diet low in red meat and rich in fresh fruits and vegetables can also curtail excess homocysteine levels in people genetically prone to high homocysteine (Dedoussis 2004).

Targeted Nutritional Interventions

Olive leaf & olive oil. The Olea Europaea plant is an important constituent of the diet of Mediterranean cultures, and has anti-hypertensive and anti-atherosclerotic effects (El 2009). The leaves of the olive tree contain the active compounds oleuropein and oleacein. In a human trial, 1000 mg daily of olive leaf extract reduced blood pressure (Perrinjaquet-Moccetti 2008). Pretreatment with 100 mg/kg of olive leaf extract has also been shown to reduce brain damage in a rat model of ischemic stroke (Dekanski 2011). Olive oil also contains heart-healthy compounds. A French study showed that older subjects who consume olive oil in both cooking and in dressing have a 41% lower ischemic stroke risk compared with people who never use olive oil (Samieri 2011).

Nattokinase. A 2008 study demonstrated that nattokinase, an enzyme extracted from fermented soybeans, is helpful in reducing blood pressure in patients with hypertension (Kim 2008). The participants that received 2000 fibrinolytic units (FU) of nattokinase daily for 8 weeks had a reduction in systolic and diastolic pressure of almost 6 mmHg and 3 mmHg, respectively. Nattokinase breaks apart the protein fibrinogen, which contributes to blood viscosity and clotting. This reduction in blood viscosity may be one of the ways that nattokinase affects blood pressure. Nattokinase also inhibits the elevation of angiotensin II in the bloodstream (Fujita 2011).

L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine. L-carnitine is an essential co-factor in the metabolism of lipid molecules into cellular energy. L-carnitine has been shown to be neuroprotective in rat models of ischemic stroke (Wainwright 2003). Laboratory studies on human tissue specimens demonstrate that L-carnitine causes vasodilation. In one laboratory study, L-carnitine selectively inhibited a platelet-activating factor, demonstrating that L-carnitine has a protective effect against thrombosis in ischemic stroke. In a sample of 9 ischemic muscle specimens from 5 patients with vascular disease, L-carnitine levels were low, but were restored 2 days after a single injection followed by a 30-minute infusion of propionyl-L-carnitine (Andreozzi 2009). In an animal model of ischemic stroke, pre-treatment with acetyl-L-carnitine decreased brain damage (Zhang 2012).

Vinpocetine. Vinpocetine is derived from the chemical vincamine, which is an extract from the leaves of the lesser periwinkle plant. Since its synthesis in the 1960s, vinpocetine has shown both neuroprotective and cerebral blood-flow-enhancing properties. It is widely used in cerebrovascular disease in Japan, Hungary, Poland, Russia, and Germany (Patyar 2011).

Vinpocetine has neuroprotective effects due to its ability to block sodium channels and calcium channels in brain cells, preventing excitotoxicity and death of brain tissue (Bereczki 2008). Animal models reveal a role for vinpocetine in blocking inflammatory processes. This is significant because chronic inflammation leads to endothelial dysfunction and atherosclerosis, increasing the risk for stroke. In an animal model of ischemic stroke, damage to a brain area known as the hippocampus was reduced from 77% in untreated animals to 37% in animals treated with vinpocetine (Patyar 2011). Note: Women who are pregnant or could become pregnant should not use vinpocetine.

Vitamin D. Evidence from clinical trials suggests that vitamin D plays a modest role in blood pressure control (Witham 2009). Vitamin D regulates blood pressure by modulating calcium-phosphate metabolism, controlling endocrine glands, and improving endothelial function. Vitamin D deficiency appears to be an independent risk factor for stroke incidence in Japanese-American men (Kojima 2012) and Korean men (Park 2012). A recent study also showed that individuals whose vitamin D levels were greater than 30 ng/mL had the lowest incidence of heart attack and stroke (Park 2012). Vitamin D may also promote normal insulin metabolism (Houston 2010).

Vitamin B6, B12, and Folic Acid. B-vitamin therapy has been shown to lower homocysteine levels and independently reduce stroke risk (Saposnik 2009). Homocysteine levels can become elevated when serum B12 level are below 400 pmol/L (Spence 2011). Analysis of data on 5522 participants in a large trial to assess the role of B-vitamins in stroke risk reduction (the HOPE-2 trial) demonstrated that treatment with folic acid and vitamins B6 and B12 lowered plasma homocysteine levels and overall stroke incidence. In this study, the incidence of both ischemic and hemorrhagic stroke was lower in the vitamin group compared to the placebo group (Saposnik 2009). A 2012 review of 19 different studies found that B-vitamin supplementation reduces stroke risk by approximately 12% (Huang 2012a). Another 2012 study supported those findings by demonstrating that supplementation with folic acid can reduce stroke incidence by 8% (Huo 2012).

Omega-3 fatty acids. Omega-3 fatty acids are found in certain fat sources such as cold-water fish and flaxseed oil (Houston 2010). Studies have demonstrated that omega-3 fatty acids help regulate blood pressure and reduce platelet aggregation, inflammation, LDL-cholesterol, and other atherosclerosis risk factors (AHA 2010). A 2006 review article indicated that omega-3 fatty acids have a significant protective effect against cerebrovascular disease (Wang 2006). In a mouse model of ischemia, 3 months of treatment with docosahexaenoic acid (DHA) blunted inflammatory responses after an ischemic stroke and decreased brain damage (Lalancette-Hebert 2011).

Omega-3 intake may slow the progression of atherosclerosis by reducing plasma triglyceride levels (Mozaffarian 2011). In short-term clinical trials, consumption of omega-3 fatty acids stimulated nitric oxide production, which enhances the dilation of arteries and improves blood flow throughout the body. Omega-3 fatty acids have also been shown to improve endothelial function and prevent abnormal heart rhythms (arrhythmias) (Mozaffarian 2011; Reiffel 2006; Singer 2004). The American Heart Association suggests that some people may not get enough omega-3 fatty acids through diet alone and that these individuals should consider taking a dietary supplement (AHA 2010).

Garlic. Some clinical trials have found that increased consumption of garlic can lower blood pressure in hypertensive patients. Consumption of approximately 10 000 mcg of the active ingredient allicin, the amount contained in about four cloves of garlic, per day appears to be necessary to lower blood pressure (Houston 2010). A review of studies demonstrated that garlic consumption appears to lower systolic and diastolic blood pressure by an average of 16 and 9 mmHg, respectively (Reinhart 2008).

Dehydroepiandrosterone (DHEA). DHEA, an endogenous steroid hormone derived from cholesterol, is the most abundant circulating steroid in humans. DHEA improves arterial dilation and protects against endothelial dysfunction, a risk factor for stroke (Kawano 2003). In a study of over 300 postmenopausal women, higher levels of DHEA-s, a major metabolic derivative of DHEA, were associated with less severe stroke (Pappa 2012).

Vitamin C. Vitamin C, also known as ascorbic acid, is a water-soluble antioxidant that improves endothelial function. Numerous observational and clinical studies have documented that dietary intake of vitamin C can lower blood pressure and heart rate. Evaluation of published clinical trials has shown that intake of 250 mg vitamin C twice daily lowered systolic and diastolic blood pressure by about 7 mmHg and 4 mmHg, respectively. Vitamin C may lower blood pressure by reducing binding of angiotensin II to its receptor. Vitamin C also appears to enhance antihypertensive effects of some blood pressure medications (Houston 2010).

Flavonoids. Flavonoids are naturally occurring antioxidants found in fruits, vegetables, red wine, and tea (Houston 2010). A 2012 study showed that increased intake of flavonoids is associated with reduced risk of ischemic stroke in women, and that consumption of citrus fruits can reduce overall stroke risk (Cassidy 2012). An animal model showed that a single intravenous dose of the flavonoid resveratrol improved cerebral blood flow by 30% and protected against ischemia-induced brain damage (Lu 2006).

Rutin. Rutin is a flavonoid that occurs naturally in buckwheat and some fruits (eg, apples) (Kreft 2006; Lata 2009). Rutin inhibits an enzyme called protein disulfide isomerase (PDI), which participates in blood clot formation. Among nearly 5000 agents screened as potential PDI inhibitors in one study, rutin was one of the most potent (Jasuja 2012). An animal model showed that rutin inhibits the formation of blood clots (Jasuja 2012). ​

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Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the treatments discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.

The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. The publisher has not performed independent verification of the data contained herein, and expressly disclaim responsibility for any error in literature.

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