Thursday, February 21, 2008

Neurological-Restless Leg Syndrome

Fighting the Urge


A disorder of the central nervous system, restless leg syndrome (RLS) is characterized by the irresistible urge to move the legs. This urge usually occurs during sleep or periods of inactivity and is frequently accompanied, or caused by, uncomfortable and unpleasant sensations that are partially or completely relieved by movement. Some of the words patients with RLS use to describe the feeling include “creepy-crawly,” “burning,” “tingling,” “twitching,” and “painful.”

The symptoms of the condition tend to occur at exactly the wrong time—when people are trying to relax or sleep. As quality and quantity of sleep become an issue, daytime fatigue and exhaustion follow, affecting work and mental performance (National Institutes of Health 2005).

Although the cause of RLS is unknown, researchers believe that it results from abnormal functioning of the central nervous system. RLS produces excitability in a region of the brain known as the subcortical area. This excitability is caused by a dysfunction in a nerve-signaling chemical called dopamine (Allen RP et al 2001b; Odin P et al 2002). Dopamine is a central neurotransmitter that is particularly important in the regulation of movement.

The exact prevalence of RLS is undetermined. It may be more common than is currently thought because people may not report it to their physicians, and some physicians may wrongly attribute the symptoms to nervousness, insomnia, stress, arthritis, muscle cramps, or aging (National Institutes of Health 2005). RLS is associated with diabetes and smoking. Studies show that it affects between 1 percent and 5 percent of younger adults and up to 20 percent of adults older than 60 years (Kasper DL et al 2005). There is also a clear familial connection; about one third of patients with RLS have multiple family members who are also affected by the condition (Kasper DL et al 2005). The prevalence of RLS closely correlates to race. It is rare among Asians (0.1 percent to 5 percent) (Chaudhuri KR 2003) and most common among people of northern European descent.

Up to 90 percent of patients with RLS experience a more common condition known as periodic limb movement disorder (PLMD), which is especially common in patients who are undergoing dialysis (Rijsman RM et al 2004). PLMD is characterized by involuntary leg twitching or jerking movements during sleep that typically occur every 10 to 60 seconds, sometimes throughout the night. The symptoms cause repeated awakening and severely disrupted sleep. Unlike RLS, the movements caused by PLMD are involuntary. Although many patients with RLS also develop PLMD, most people with PLMD do not experience RLS (National Institutes of Health 2005).
Although the exact cause of RLS is unknown, a number of conditions are associated with it including:

1)Iron deficiency

2)Low dopamine levels

3)Lesions within the spinal cord or peripheral nerves

4)Pregnancy-related deficiencies in iron, folate, and magnesium (Lee KA et al 2001;

5)Manconi M et al 2004)

6)Kidney disease, particularly end-stage kidney disease

7)Medications, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, lithium, and caffeine (National Heart, Lung, and Blood Institute 2000)

RLS is classified into primary and secondary forms. Primary RLS occurs in the absence of other conditions. It tends to onset earlier and is associated with a single genetic defect (Desautels A et al 2001). Secondary RLS is linked to iron deficiency and other conditions such as pregnancy, anemia, kidney disease, and brain dysfunction (Bonati MT et al 2003; Rye DB 2004; Stiasny-Kolster K et al 2004). RLS is also associated with hyperalgesia (increased pain sensation), which is most likely connected to dopamine activity.

Iron and Dopamine Abnormalities

The brains of patients with RLS exhibit abnormalities in the relationship between iron and dopamine. An enzyme involved in dopamine synthesis—tyrosine hydroxylase—requires iron for proper function. In animal studies, iron insufficiency appears to cause abnormal dopamine function (Allen RP et al 2001a). It is believed that patients with RLS may have impaired iron absorption in the brain (Connor JR et al 2003). The iron deficiencies are pronounced in certain parts of the brain that help control body movement. In autopsies of people with RLS, iron levels have been particularly low in a region of the brain called the substantia nigra (Connor JR et al 2003).

Further evidence of the relationship between iron deficiency and RLS is found in the three major secondary causes of RLS—end-stage renal disease, pregnancy, and iron deficiency, which all involve low levels of iron (Allen RP et al 2001b).

Diagnosis and Conventional Treatment

The diagnosis of RLS begins by excluding other conditions, such as anemia, diabetes, kidney disease, and iron deficiency. Electromyography and nerve conduction studies are sometimes recommended to measure electrical activity in muscles and nerves; Doppler ultrasonography can be used to evaluate muscle activity in the legs.

Such tests can document any damage or disease in nerves and nerve roots (such as peripheral neuropathy and radiculopathy) or other leg-related movement disorders.

In some cases, sleep studies such as polysomnography (a test that records the patient's brain waves, heartbeat, and breathing for an entire night) are undertaken to identify the presence of PLMD (National Institutes of Health 2005). Actigraphy, a sleep test in which a wristwatch-like device is applied to the wrist or ankles to record and measure muscle movements during sleep, may also be recommended.

Once RLS is diagnosed, it can be treated with medications (Rye DB 2004 Dec). Some of the more common conventional medications used to treat RLS include:

Levodopa—Levodopa (L-dopa) is a form of dihydroxyphenylalanine, the immediate precursor to dopamine. However, unlike dopamine, it can be taken orally and cross the blood-brain barrier. Once inside brain cells, the medication converts to dopamine. L-dopa is usually given with other medications that inhibit its effect outside of the central nervous system (Odin P et al 2002). The disadvantages of L-dopa are its short-term effects (1 to 2 hours) and a side effect known as augmentation, whereby RLS symptoms appear earlier in the day and with increasing severity (Odin P et al 2002). L-dopa can also cause nausea.

Dopamine agonists—Alternatives to L-dopa including dopamine agonists such as cabergoline, ropinirole, and pramipexole. In general, dopamine agonists have milder augmentation symptoms compared to L-dopa and are considered the treatment of choice (Kasper DL et al 2005). They have had success in relieving symptoms in more than 70 percent of patients (National Institutes of Health 2005). L-dopa and dopamine agonists can significantly reduce the number of limb movements per hour and improve the subjective quality of sleep.

Sleep agents—Minor tranquilizers such as benzodiazepines (Kasper DL et al 2005).

Anticonvulsant medications—Medications that slow convulsions (Kasper DL et al 2005).

Some medications that induce or worsen RLS include atypical neuroleptic drugs, caffeine, classical neuroleptic drugs (such as D2 receptor antagonists), H2-blocking agents, lithium, metoclopramide, and mianserin (Odin P et al 2002).

Nutrients to Help Resist the Urge
Because RLS has been associated with specific nutrient deficiencies, researchers have studied the effects of supplementation in patients who have RLS. The results have been promising.

Iron
A deficiency in iron can trigger RLS. Not only can iron levels be low in people with RLS, but iron storage in the body appears to be abnormal due to a low level of a protein called ferritin and a high level of the transporter protein transferrin. Transferrin transports iron in cerebrospinal fluid and in plasma. Fewer symptoms of RLS are apparent in people with ferritin levels greater than 50 micrograms per liter (mcg/L) (Sun ER et al 1998). A ferritin deficiency can arise from low iron intake, inadequate absorption, or excessive blood loss.

Symptoms of RLS can improve or be resolved completely through oral or intravenous iron supplementation. Studies showed relief from symptoms of RLS after supplementation with 200 milligrams (mg) of intravenous iron administered over a few days (Allen RP et al 2001a,b; Nordlander NB 1953; O'Keeffe ST et al 1994).

The absorption of iron from food and supplements can vary based on the form of iron used. Intestinal uptake can vary based on biological need. Heme (deep red, ferrous component of hemoglobin) sources of iron, such as red meat, are utilized the most effectively by the body. Other chelated forms of iron, such as iron protein succinylate or iron bis-glycinate are also excellent. These forms of iron can reverse anemia more quickly and with less constipation than the typical iron salts most doctors prescribe (Hertrampf E et al 2004).

Other nutrients can enhance the activity of iron in the body. Adequate vitamin A is essential, as it helps to mobilize iron from storage sites. Adding zinc to iron supplements may increase hemoglobin levels more than taking iron supplements alone. In the same way, taking 250 to 500 mg of vitamin C can raise the absorption of iron, although it may also increase its side effects. Iron absorption will increase if it is ingested on an empty stomach (Allen RP et al 2001a).

Folic acid

Folic acid is the synthetic form of folate, the water-soluble B vitamin that helps produce and maintain new cells in part through the creation of DNA and RNA. Folate can even protect cells from changes to DNA (Mattson MP et al 2003). Also, folate is needed to make red blood cells and prevent anemia (National Kidney and Urologic Diseases Information Clearinghouse 2005).

RLS is related to folate deficiency, particularly in the form of RLS that is associated with familial inheritance and with pregnancy. Patients with this type of RLS have benefited from intake of between 5 and 10 mg of folic acid per day, or from taking folinic acid (Botez MI 1976; Botez MI et al 1977). People taking folic acid should ensure that they receive at least 500 to 1000 mcg of vitamin B12 each day to make sure the folic acid isn’t masking a vitamin B12 deficiency.

Some people do not have the enzyme 5-methyltetrahydrofolate reductase, which converts folate into its bioactive form. These individuals often present with high levels of homocysteine and associated health concerns such as heart disease and depression; folinic acid (5-formyltetrahydrofolate) is the only option. It is a metabolically active form of folate, capable of boosting levels of the coenzyme forms of the vitamin in circumstances where folic acid has little to no effect (Kelly GS 1998).

Magnesium

Magnesium has also been shown to partly relieve RLS. Particularly for people with nighttime RLS, 250 mg of magnesium citrate taken before bed may decrease symptoms and aid sleep. Therapeutic dosages range from 250 to 800 mg of elemental magnesium a day (Rijsman RM et al 1999).

Life Extension Foundation Recommendations

Eating a well-balanced diet and getting adequate amounts of iron, folate, magnesium, and vitamin E may help avert or reduce symptoms of RLS. It is also recommended that patients not smoke (Mountifield JA 1985) and reduce their intake of (or avoid entirely) caffeine, sugar, and alcohol (Lutz EG 1978).

To help monitor healthy blood levels of nutrients, patients with RLS might consider having the following blood tests:

1)Complete blood cell (CBC) count and chemistry panel

2)Serum ferritin

3)Red blood cell (RBC) count

4)Magnesium

5)Vitamin B12

The Life Extension Foundation suggests the following nutrients may be helpful in managing RLS:

Folic acid—400 to 800 mcg daily. Take with 500 to 1000 mcg of

vitamin B12 daily in the form of methylcobalamin.

Magnesium citrate—100 to 250 mg before bed, depending on the severity of the symptoms.

Iron—Dosing is based on individual needs. Better forms are iron protein succinylate or iron bis-glycinate. Take with 250 to 500 mg of vitamin C to help the body absorb the iron.


Restless Leg Safety Caveats

An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

Folic acid

1)Consult your doctor before taking folic acid if you have a vitamin B12 deficiency.

2)Daily doses of more than 1 milligram of folic acid can precipitate or exacerbate the neurological damage caused by a vitamin B12 deficiency.

Iron

Do not take iron if you have hemochromatosis or hemosiderosis.
Consult your doctor before taking iron supplements if you have an elevated serum ferritin level, alcoholic cirrhosis, a pancreatic insufficiency, or a history of chronic liver failure, chronic alcoholism, gastritis, peptic ulcer disease, or gastrointestinal bleeding.

Magnesium

1)Do not take magnesium if you have kidney failure or myasthenia gravis.

Vitamin B12 (cyanocobalamin)

1)Do not take cyanocobalamin if you have Leber's optic atrophy.

Wednesday, February 20, 2008

RESPIRATORY-ASTHMA

Asthma is the most common chronic pulmonary disorder in the United States. The condition is characterized by hypersensitivity and inflammation of the lung’s airway (bronchial) tissue, and asthma attacks can leave a person gasping for breath. While most cases are mild, more than 5000 deaths are attributed to asthma attacks each year, according to the American Academy of Allergy, Asthma and Immunology (AAAAI 2006).

The incidence of asthma cases has surged in recent years, although researchers aren’t sure exactly why. According to some studies, up to 5 percent of the US population is affected by asthma, with half of these cases developing before age 10 (Kasper DL et al 2005). Asthma attacks can be triggered by allergies and environmental irritants. Scientists have also discovered links between asthma and other diseases and conditions, including gastroesophageal reflux disease (GERD) and obesity (Flaherman V et al 2006).

People with asthma usually rely on medications to control their condition. During severe asthma attacks, patients need “rescue medications,” which are designed to restore airflow. When attacks aren’t occurring, many asthmatics take “maintenance medications,” or medications that have been shown to reduce the risk of acute asthma attacks. Both classes of medications have side effects, but because of the more severe side effects (such as high blood pressure) associated with rescue medications, the goal of conventional therapy is to prevent attacks with the right dosages of maintenance drugs.

Life Extension takes this philosophy one step further. Under the best circumstances, asthmatics could control their condition without the use of any medications, completely avoiding the side effects associated with prescription drugs. In recent years, researchers have learned a great deal about asthma and natural methods to inhibit the underlying inflammatory cascade that causes so much misery. Life Extension has also uncovered evidence that a common herbal extract, butterbur, is a highly effective asthma therapy. Finally, oxidative stress, which can wreak havoc with cells, has been linked to asthma, thus antioxidants have a definite role in therapy.

Lifestyle changes can also affect the frequency of asthma attacks and their severity. People who smoke are strongly encouraged to quit. Numerous smoking-cessation strategies are available, from nicotine replacement to group therapy. It may also help to reduce exposure to second-hand smoke and air pollution whenever possible. There is an increased risk of asthma among people who live in heavily populated urban areas. Finally, seeking treatment for diseases such as GERD and obesity may help reduce the severity of asthma.

Understanding Asthma: Inflammation and Oxidative Stress

Asthma is primarily a disorder of the bronchial tubes, the airways that connect the windpipe (trachea) and the lungs. The bronchial tubes are surrounded by smooth muscle. The tubes themselves are lined with mucus glands and contain inflammatory immune-system cells called mast cells, lymphocytes, and eosinophils. When activated, these cells produce inflammatory mediators such as histamine and leukotrienes, which bind with receptors on cells within the bronchial tubes.

During as asthma attack, a cascade of events is launched that results in the production of histamine and leukotrienes. Leukotrienes are derived from the inflammatory arachidonic acid. These inflammatory mediators cause a host of changes in bronchial tissue: they trigger a dramatic increase in mucus secretion and a simultaneous rapid constriction of the bronchial smooth muscle, which narrows the bronchial tubes and reduces the amount of air that can pass through them. Over the course of the subsequent few hours, inflammatory cells move into the area, capillaries begin to leak fluid, and direct tissue damage occurs, triggering further inflammation and swelling. The net result is wheezing and coughing and eventual trapping of air in the alveoli (a tiny, thin-walled, capillary-rich sac in the lungs, or air sac) and smaller airways. This air trapping is most dangerous to the asthmatic because it progressively limits the amount of air that can be exchanged between the lungs and the blood stream, eventually causing rising carbon dioxide levels and falling oxygen levels. The increased muscular effort required to move air increases oxygen demand, tissue metabolism, and acid production, eventually resulting in exhaustion and, in extreme cases, respiratory collapse and arrest.

Why the bronchial tubes become so sensitive in asthmatics is not fully understood, but research suggests that immune-system cells known as T cells play a central role. Some T cells induce inflammation to fight off a foreign threat, while others reduce inflammation once the threat has subsided. Conditions such as asthma, in which the body overreacts to threats, may be related to an imbalance or malfunction of these and other immune-system components (Tosca MA et al 2003; Howard TD et al 2002; Ray A et al 2000).

The idea behind nutritional supplementation is to disrupt this inflammatory cascade whenever possible. For example, omega-3 fatty acids have been shown to inhibit the production of arachidonic acid, which reduces the concentration of inflammatory leukotrienes (Wong KW 2005). Other nutrients, such as curcumin, interfere with other causative factors in the inflammatory cascade, such as inhibiting nuclear factor kappa beta and an enzyme that converts arachidonic acid to leukotriene B4.

It is very important that asthmatics take whatever steps are necessary to control their condition. Unchecked, asthma can cause permanent damage to the bronchial tubes, a situation known as airway remodeling. Under constant inflammatory stress, the bronchial tubes undergo structural change. The bronchial tubes thicken; the surrounding smooth muscle increases; the epithelium (the fragile layer of cells lining the bronchial tubes) sloughs off into the passageways; and mucus production increases. These changes can permanently reduce lung function and increase the frequency of asthma attacks (Larj MJ et al 2004; Nakagawa T et al 2004).

Scientists are also beginning to better understand the interaction between allergies, asthma, and oxidative stress. Oxidative stress occurs when highly reactive molecules, known as free radicals, interact with molecules within the body, especially DNA and mitochondrial membranes. Experimental evidence suggests that some pollutants, such as vehicle exhaust, may produce oxidative stress in the bronchial tubes (Gilmour MI et al 2006). Studies suggest that dietary supplementation with precursors of glutathione (an internal antioxidant), such as cysteine and alpha-lipoic acid, can enhance the pulmonary defenses, thus countering oxidative stress (Bridgeman MM et al 1991).

Interestingly, asthma and GERD seem to be strongly associated. GERD is a chronic condition in which partially digested stomach contents, including acid, flow backward into the esophagus. Heartburn and other symptoms usually result. Although the relationship between asthma and GERD is unclear, there is evidence for two related mechanisms. The irritation by acid of nerve receptors in the esophagus may produce a reflex irritability in the vagus nerve, producing increased sensitivity to cough-inducing stimuli in the lungs. Alternatively (or in addition), microscopic food particles and acid may be aspirated into the lungs from the refluxed material, triggering the initial round of inflammation that sets off the attack (Jiang SP et al 2005). Both mechanisms involve an initial inflammatory stimulus from the irritating stomach contents.

Good nutrition and eating habits are important in the prevention of GERD. For more information on how to treat GERD, see the chapter Gastroesophageal Reflux Disease.

Diagnosis and Medications Used to Treat Asthma
There is no single means of diagnosing asthma. A patient’s medical history, including any existing or former breathing difficulties, allergies, or skin conditions, such as eczema, are important clues. Family medical history is also important because asthma tends to run in families. Very often, patients have a history of chronic or recurrent cough for months or years before the diagnosis of asthma is finally made.

Physicians may perform pulmonary function tests to determine various parameters of lung function, such as total volume of air and the rate and force of expiration (breathing out). They may also perform a “bronchoprovocation” test, which involves the induction of a minor asthma attack by the use of histamine or some other substance.

Medication to treat asthma can be categorized as short-acting rescue medication or as maintenance medication. Rescue medications are designed to provide immediate relief from the symptoms of an asthma attack. Long-acting control medications reduce inflammation and prevent asthma attacks from occurring. Asthma experts agree that the major goal of medication is to optimize long-term control medications so that rescue medications, with their many side effects, can be minimized or eliminated (Simons FE 1999).

Bronchodilators are usually used as rescue medications (except when combined with steroids for long-term maintenance). They work by relaxing the bronchial muscles. These medications can be inhaled, injected, or taken orally. Bronchodilators are of three types:

Beta-2 agonists (e.g., albuterol). Short-acting beta-2 agonists are meant only for immediate relief of symptoms and may be given in conjunction with a maintenance medication. Long-acting beta-2 agonists are sometimes prescribed as stand-alone maintenance medications. Numerous brands of beta agonists are on the market.

Anticholinergics. These medications block the action of acetylcholine, a neurotransmitter. They produce effects similar to those of the beta-2 agonists, with a similar side effect profile.

Theophylline. Chemically similar to caffeine, this drug is not a first-line treatment because it is not as effective as other medications. Theophylline use has been associated with vitamin B6 deficiency (Shimizu T et al 1996).

Although effective for short periods of time, bronchodilators can be stressful for the body. These medications mimic the action of adrenaline, which is released during the “fight or flight” response and causes dilation of the bronchial tubes. Side effects include rapid heart rate, increased blood pressure, increased blood sugar levels, irregular heart rhythms, and a variety of other responses (Nizet TA et al 2004; Wraight JM et al 2004; Rodrigo GJ et al 2002).

In general, however, the goal of asthma therapy is to reduce the need for rescue medications by keeping patients stable on maintenance medications. Maintenance medications include the following:

Corticosteroids. These medications reduce inflammation by down-regulating production of inflammatory cytokines. Corticosteroids usually require several hours to onset, with peak effects not seen for one to three days. These medications can be inhaled or administered via nasal spray but also may be taken orally or injected.

Commonly used inhaled medications include Beclovent® (beclomethasone), Pulmicort® (budenoside), and AeroBid® (triamcinolone). Nasally administered medications include Beconase® (beclomethasone), Rhinocort® (budesonide), Flonase® (fluticasone), and Nasonex® (mometasone).

Long-term use of systemic (oral or injected) corticosteroids is associated with cataracts and glaucoma, osteoporosis, muscle weakness, chemical-induced diabetes, hypertension, adrenal gland dysfunction, and edema. Corticosteroids also deplete the body of calcium, magnesium, potassium, and zinc and may lead to osteoporosis. Some of these nutrients should be supplemented during long-term corticosteroid therapy (Banov CH 2004). Inhaled corticosteroid medications produce far fewer side effects because of the low doses of steroids involved. These drugs are associated with local side effects, however, such as thinning of the oral or nasal mucus membranes and yeast infections.

Leukotriene modifiers. These make up a relatively new class of drug that prevents or reduces inflammation by inhibiting the production or activity of leukotrienes. Leukotrienes are synthesized from arachidonic acid by lipoxygenase enzymes. Commonly used leukotriene modifiers include Singulair® (montelukast), Accolate® (zafirlukast), and Zyflo® (zileuton).

Mast cell stabilizers. These medications prevent mast cells (a type of immune cell) from releasing histamines, which can lead to an allergic reaction or an asthma attack. Mast cell stabilizers are less effective than other medications and are not frequently prescribed. They are usually reserved for individuals who cannot tolerate the side effects of other asthma medications.

A new type of treatment targets a class of immunoglobulins called immunoglobulin E, which activates mast cells and other inflammatory cells that trigger asthma attacks. Several trials have demonstrated the promise of this product in allergic asthma activity and as a therapy that may help patients reduce or avoid corticosteroids (Boushey HA Jr 2001). It is designed for use in moderate to severe asthma only. Side effects, which may be serious, include allergic reactions, hypotension (low blood pressure), arthritis, and kidney failure.

Butterbur: An Herbal Approach to Asthma
Butterbur (Petasites hybridus) is a perennial shrub that has been used since ancient times to treat a variety of conditions. As far back as the 17th century, butterbur was used to treat cough, asthma, and skin wounds (MMWR 2001). Today, researchers have uncovered the mechanism of action that makes butterbur effective.

Scientists have identified and isolated the compounds in butterbur that help reduce symptoms in asthma. Called petasins, these chemicals inhibit leukotrienes and histamines, which are responsible for symptom aggravation in asthma (Thomet OA et al 2002).

So far, a few research teams have examined butterbur’s effectiveness in asthmatics, with encouraging results. In one open trial of 64 adults and 16 children and adolescents, asthma patients were treated for two months with butterbur extract, followed by an optional two-month open trial. They were measured throughout the study for the severity and frequency of asthma attacks. According to researchers, all the measured symptoms improved throughout the study, and 40 percent of patients were able to reduce their intake of traditional asthma medications (Danesch UC 2004).

Another study examined butterbur in conjunction with inhaled corticosteroid therapy. In this trial, 16 asthmatics were given butterbur or placebo while they continued their constant dose of inhaled steroid medications. Butterbur therapy, at 50 mg daily, was shown to reduce several measures of symptoms, leading researchers to conclude that butterbur is an effective adjunct therapy to corticosteroids. They called for further study of butterbur as a stand-alone therapy for mild asthmatics, who might be able to forgo their prescription medications (Lee DK et al 2004).

Antioxidant Therapy
Researchers are also finding that antioxidants have the unique power to reduce lung and bronchial damage in people with asthma. The lungs are at particular risk for oxidative damage because their primary function is the exchange of oxygen and waste gases. Antioxidants protect the body’s tissues by scavenging oxidant molecules and rendering them less harmful. Antioxidants can be ingested, as in the case of vitamin C, or produced internally, as in the case of glutathione.

Nutritional approaches, although often slow to act in advanced disease, can enhance the effect of medical therapy by interfering with the inflammatory process and reducing oxidation, thereby potentially reducing the need for higher doses of medication. However, patients should always consult a physician before changing their diet or medication therapy.

Antioxidants (vitamins C, E, and A). A number of studies have suggested that consuming antioxidants such as vitamins C, E, beta-carotene, flavonoids, selenium, and other nutrients reduces the risk of bronchoconstriction associated with asthma.

For instance, studies have shown that vitamin C and possibly vitamin E supplementation can alleviate the severity of asthma symptoms (Ford ES et al 2004; Rubin RN et al 2004; Wijnhoven HA et al 2003; Trenga CA et al 2001; Fogarty A et al 2000; Hijazi N et al 2000; Seaton A et al 2000). Dietary supplementation with vitamin C and vitamin A (the substances that give fruits and vegetables their color) has also been associated with reduced susceptibility to asthma attacks. Other studies have demonstrated that vitamin C or E supplementation may be a valuable addition to the treatment of patients with allergic rhinitis (otherwise known as hay fever) and asthma.

Dietary supplementation of vitamin C has also been found to help a specific form of asthma called exercise-induced asthma (EIA). People with EIA are usually symptom free when not exercising. Studies have found that 1 or 2 g vitamin C daily diminished episodes of EIA. (Jaber R 2002).

Flavonoids. Flavonoids are the brightly colored pigments found in most fruits and vegetables. In plants, they assist with photosynthesis, but when consumed, they have antioxidant properties and have been associated with improved lung function. One study (Knekt P 2002) demonstrated that a high dietary intake of the flavonoids quercetin (found in wine, tea, and onions), naringenin (found in oranges and grapefruit), and hesperetin (found in oranges and lemons) was associated with a lower prevalence of asthma. It is interesting to note that quercetin has a chemical structure similar to cromolyn, a mast cell stabilizer sometimes used to treat asthma (Braunwald E et al 2001).

Other bioflavonoids are reported effective in the treatment of asthma. Researchers recently looked at the effects of lycopene (the red pigment found in tomatoes and some fruits) on patients with EIA. More than half of patients (55 percent) showed improvement in the amount of air they could exhale (Neuman I et al 2000). Other studies found that pycnogenol (an extract of French maritime pine bark) appeared to reduce asthmatic symptoms (Rohdewald P 2002).

Ginkgo biloba. Ginkgo biloba, a flavonoid-rich extract of leaves of the Ginkgo biloba tree, may be an effective asthma therapy, according to the results of several studies (Mahmoud F 2000; Li MH et al 1997).

Vitamin B6. Only a limited number of studies have been conducted on vitamin B6 as it pertains to asthma (Sur S et al 1993). Although the results did not show a clear improvement in all asthma cases, researchers found that the asthma drug theophylline appeared to lower the blood level of vitamin B6. Theophylline is rarely prescribed in the United States. In cases when it is prescribed, a patient’s vitamin B6 levels should be checked periodically to determine if supplementation is needed.

RESPIRATORY-ASTHMA

Minerals and Fatty Acids to Relieve Asthma Suffering

Selenium. Studies have shown that individuals with chronic asthma may suffer from a selenium deficiency, increased oxidative stress, and decreased glutathione activity (Allam MF et al 2004; Fogarty A et al 2000). Selenium is an essential dietary mineral that plays a vital role in activating glutathione. In a recent study, women with relatively low blood selenium levels during pregnancy gave birth to infants with a higher incidence of asthma (Shaheen SO et al 2004). These results suggest that dietary supplementation with selenium may diminish the susceptibility to asthma.

Magnesium. Several studies have indicated that patients with asthma have lower levels of magnesium within the cells lining the airways. When daily magnesium supplementation was given to children with mild to moderate asthma, a significant decrease in the use of rescue beta-agonist inhalers was demonstrated (Bede O et al 2003). These results suggest that intracellular magnesium levels are associated with the severity of asthma and the frequency of asthma attacks. Maintaining normal magnesium levels appears to be an important component of asthma therapy.

Zinc. Zinc appears to affect apoptosis, or “programmed cell death.” All cells contain genetic code that determines when they should die. A defect may cause cells to die prematurely, leading to inflammation, which can trigger an asthma attack. Zinc may have a role in preventing premature cell death in the asthmatic lung, which might have a protective effect (Truong-Tran AQ et al 2003). However, more research is necessary to determine the role zinc might play in the lungs generally and asthma specifically (Richter M et al 2003).

Calcium and vitamin D. Steroid use, particularly oral or systemic, is associated with the development of osteopenia (reduced bone density) and eventual osteoporosis (a condition in which bones lose mass and density) (Braunwald E et al 2001; Gennari C 2001). When asthma patients are on long-term oral steroid therapy, supplemental calcium and phosphate are recommended to prevent osteopenia. Calcium citrate contains the highest available elemental calcium in capsule form (Gennari C 2001). Periodic bone densitometry evaluation is recommended for assessing the development of osteoporosis (Mortensen L et al 1998).

Preventing osteopenia involves the oral intake of 1200 mg elemental calcium along with supplemental vitamin D (1000 IU) daily. In the event that osteoporosis develops, a bisphosphonate is usually added to the therapy (Gennari C 2001).

Omega-3 and other polyunsaturated fatty acids. Omega-3 fatty acids, also known as fish oils, may play a role in the prevention of asthma by reducing the tendency toward inflammation. A study of the immune status of neonates showed that the neonatal production of inflammatory cells associated with asthma was significantly decreased in infants of supplemented mothers (Dunstan JA et al 2003).

The current literature is supportive of dietary omega-3 polyunsaturated fatty acid use as a means of modifying asthma susceptibility and severity. However, fish oil supplementation has been associated with a worsening of asthma in aspirin-sensitive asthmatics (Jaber R 2002). Therefore, it should not be used by this subpopulation of asthmatics. If asthma patients are unsure about their sensitivity to aspirin, they should check with their doctor before taking fish oil supplements.

Borage oil. Borage oil, an herbal extract, contains a high percentage of a substance called gamma-linolenic acid (GLA). GLA is a type of fat that has been shown to regulate leukotrienes, biochemicals that can trigger asthma attacks. An asthma medication called zileuton works in much the same way.

Although more research must be done, borage oil, which contains GLA, may prove to be an attractive alternative as a dietary leukotriene-modifying therapy. Researchers found that daily supplementation of GLA had an impact on leukotrienes and warranted further study (Ziboh VA et al 2004).

Curcumin. Curcumin inhibits nuclear factor kappa beta, a major component for translating inflammatory stimuli into actions such as production of cytokines and changes in inflammatory cell function. Curcumin has been found to reduce the inflammatory responses of lymphocytes in human asthmatics, and in a laboratory animal model of asthma, treatment with curcumin reduced airway hyperresponsiveness (Kobayashi T et al 1997).

Life Extension Foundation Recommendations

Asthma is closely related to environmental health and allergies. People who suffer from allergies should obtain a high-quality high-efficiency particulate air filter in the home and avoid potential allergens whenever possible. Exercise may help improve lung function, but asthma patients should be aware that exercising in cold or polluted air (such as a winter morning run) can aggravate their condition.

Some asthma patients are given corticosteroids to reduce inflammation. Because these drugs can cause osteoporosis, people taking any form of corticosteroid should also supplement with calcium and vitamin D to support strong bones. The following dosages are suggested:

1)Calcium—1200 milligrams (mg) daily

2)Vitamin D—1000 international units (IU) daily

Similarly, although theophylline is rare in the United States, it is sometimes prescribed for asthma. This drug has been shown to reduce levels of vitamin B6. For people taking theophylline, the following dosage of vitamin B6 is suggested:

3)Vitamin B6—150 mg daily

Finally, all patients with asthma may be able to reduce their symptoms or reduce their medications by taking the following supplements that combat inflammation and target free radicals:

4)Butterbur—50 to 150 mg daily

5)Vitamin C—2000 to 3000 mg daily

6)Vitamin E—400 IU daily, with at least 200 mg gamma tocopherols

7)Vitamin A—5000 IU daily

8)Selenium—200 micrograms (mcg) daily

9)Quercetin—500 to 1000 mg daily (use only water-soluble quercetin)

10)Ginkgo biloba—120 mg daily

11)Lycopene—15 mg daily

12)Magnesium—340 to 1000 mg daily

13)Zinc—30 mg daily

14)EPA/DHA—1400 mg EPA and 1000 mg DHA daily

15)GLA—900 to 1800 mg daily

16)Curcumin—800 to 1600 mg daily


Product Availability
All the nutrients and supplements discussed in this section are available through the Life Extension Foundation Buyers Club, Inc.
The blood tests discussed in this section are available through Life Extension National Diagnostics, Inc.

Asthma Safety Caveats
An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

Curcumin

1)Do not take curcumin if you have a bile duct obstruction or a history of gallstones. Taking curcumin can stimulate bile production.

2)Consult your doctor before taking curcumin if you have gastroesophageal reflux disease (GERD) or a history of peptic ulcer disease.

3)Consult your doctor before taking curcumin if you take warfarin or antiplatelet drugs. Curcumin can have antithrombotic activity.

4)Always take curcumin with food. Curcumin may cause gastric irritation, ulceration, gastritis, and peptic ulcer disease if taken on an empty stomach.

5)Curcumin can cause gastrointestinal symptoms such as nausea and diarrhea.

EPA/DHA

1)Consult your doctor before taking EPA/DHA if you take warfarin (Coumadin). Taking EPA/DHA with warfarin may increase the risk of bleeding.

2)Discontinue using EPA/DHA 2 weeks before any surgical procedure.

Ginkgo biloba

1)Individuals with a known risk factor for intracranial hemorrhage, systematic arterial hypertension, diabetes, or seizures should avoid ginkgo.

2)Do not use prior to or after surgery.

3)Avoid concomitant use of ginkgo with NSAIDS, blood thinners, diuretics, or SSRI’s.
Gastrointestinal symptoms (nausea and diarrhea) may occur.

4)Allergic skin reactions may occur.

5)Elevations in blood pressure may occur.

GLA

1)Consult your doctor before taking GLA if you take warfarin (Coumadin). Taking GLA with warfarin may increase the risk of bleeding.

2)Discontinue using GLA 2 weeks before any surgical procedure.

3)GLA can cause gastrointestinal symptoms such as nausea and diarrhea.
Magnesium

Do not take magnesium if you have kidney failure or myasthenia gravis.
Quercetin

Quercetin can cause headache, mild tingling of the extremities, and gastrointestinal symptoms such as nausea.

Selenium

1)High doses of selenium (1000 micrograms or more daily) for prolonged periods may cause adverse reactions.

2)High doses of selenium taken for prolonged periods may cause chronic selenium poisoning. Symptoms include loss of hair and nails or brittle hair and nails.
Selenium can cause rash, breath that smells like garlic, fatigue, irritability, and nausea and vomiting.

Vitamin A

1)Do not take vitamin A if you have hypervitaminosis A.

2)Do not take vitamin A if you take retinoids or retinoid analogues (such as acitretin, all-trans-retinoic acid, bexarotene, etretinate, and isotretinoin). Vitamin A can add to the toxicity of these drugs.

3)Do not take large amounts of vitamin A. Taking large amounts of vitamin A may cause acute or chronic toxicity. Early signs and symptoms of chronic toxicity include dry, rough skin; cracked lips; sparse, coarse hair; and loss of hair from the eyebrows. Later signs and symptoms of toxicity include irritability, headache, pseudotumor cerebri (benign intracranial hypertension), elevated serum liver enzymes, reversible noncirrhotic portal high blood pressure, fibrosis and cirrhosis of the liver, and death from liver failure.

Vitamin C

1)Do not take vitamin C if you have a history of kidney stones or of kidney insufficiency (defined as having a serum creatine level greater than 2 milligrams per deciliter and/or a creatinine clearance less than 30 milliliters per minute.

2)Consult your doctor before taking large amounts of vitamin C if you have hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia, or erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. You can experience iron overload if you have one of these conditions and use large amounts of vitamin C.

Vitamin E

1)Consult your doctor before taking vitamin E if you take warfarin (Coumadin).

2)Consult your doctor before taking high doses of vitamin E if you have a vitamin K deficiency or a history of liver failure.

3)Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia.

4)Discontinue using vitamin E 1 month before any surgical procedure.

Zinc

1)High doses of zinc (above 30 milligrams daily) can cause adverse reactions.

2)Zinc can cause a metallic taste, headache, drowsiness, and gastrointestinal symptoms such as nausea and diarrhea.

3)High doses of zinc can lead to copper deficiency and hypochromic microcytic anemia secondary to zinc-induced copper deficiency.

4)High doses of zinc may suppress the immune system.

RESPIRATORY-BRONCHITIS (Acute)

Acute bronchitis is one of the most common reasons people in the United States seek medical care. It is important to distinguish episodes of acute bronchitis from the chronic bronchitis that is associated with chronic obstructive pulmonary disease (COPD), which is discussed elsewhere in this book.

During an episode of acute bronchitis, the tissue lining the bronchi becomes irritated and inflamed, causing increased secretion of mucus and a narrowing of the airways. This produces the characteristic cough (Treanor JJ et al 2000). For many people, the cough itself becomes an aggravating factor and worsens their condition.

Up to 95 percent of cases of acute bronchitis are caused by viral infection, with most of the rest caused by environmental irritants. The most common viral causes are influenza, parainfluenza, and the common cold viruses. Unfortunately, in many cases (up to 70 percent), antibiotics are prescribed for acute viral bronchitis, making it one of the leading situations in which antibiotics are misused. Accordingly, the American College of Physicians and the U.S. Centers for Disease Control have issued guidelines aimed at stopping physicians from automatically prescribing antibiotics to patients with acute bronchitis. According to these two organizations, the only form of bronchitis that should be treated with antibiotics is pertussis (whooping cough). However, because of the risk that acute bronchitis can also be caused by certain bacteria, some physicians will also prescribe antibiotics to certain patients to prevent further infection.

Unfortunately, there is little that can be done to stop an episode of acute bronchitis once it begins. The most common recommendation for treatment is to wait for the inflammation to subside naturally, which will relieve the coughing and other symptoms. In very severe cases, a physician might recommend medications that limit coughing, reduce mucus production, and open airways. However, many of these medications have unpleasant side effects.

Life Extension’s approach to acute bronchitis is based on two simple ideas:

1)The best defense is a good offense. Since acute bronchitis is usually caused by viral infection, every effort should be made to prevent exposure to these viruses from progressing to a full-blown infection. Life Extension has developed an aggressive program to help people avoid infections by these common viruses. To read about this program in detail, please see the chapters Influenza and Common Cold or refer to the section at the end of this chapter. It is important that people act quickly if they suspect they are coming down with a viral infection.

2)Although no medication or dietary supplement has been shown to specifically inhibit acute bronchitis, it may be possible to reduce symptoms by attacking the underlying cause of the condition, namely inflammation and its associated free radical damage and mucus production. Many nutrients have been shown to possess powerful anti-inflammatory and antioxidant capabilities.

Diagnosing and Treating Acute Bronchitis

The diagnosis of acute bronchitis can be somewhat complicated because of the many conditions it resembles. Patients with acute bronchitis typically show up at the physician’s office with a productive cough and signs of bronchial obstruction, including wheezing and breathlessness. Other symptoms may include chest pain and hoarseness. Fever is rarely associated with acute bronchitis, so if a fever is present in addition to a cough, the diagnosis is likely to be influenza or pneumonia. Other conditions that may be accompanied by a chronic cough and are sometimes mistaken for acute bronchitis include postnasal drip syndrome, asthma, and gastroesophageal reflux disease (GERD).

It is important to note that in nonsmokers, acute bronchitis should generally not be treated with antibiotics. These drugs are ineffective against the viruses that typically cause acute bronchitis, and their overuse leads to antibiotic-resistant pathogens. If therapy is warranted, physicians will likely suggest medications that control symptoms of acute bronchitis, such as coughing and mucus production. Pain relievers such as aspirin or nonsteroidal anti-inflammatories may be used, along with over-the-counter nasal decongestants. Cough suppression is not considered a primary treatment goal; the cough will resolve as the inflammation subsides and the bronchi heal.

People with acute bronchitis are also advised to drink plenty of fluids to help thin the mucus and hydrate the body. Expectorants, or medications that thin mucus, may also be recommended. The only antiviral drugs of value are those that specifically treat influenza virus in patients whose bronchitis is caused by this virus. There is some evidence that anti-influenza drugs can reduce the unnecessary use of antibiotics. Bronchodilators, which open airways, are rarely prescribed except to adults who are wheezing and have evidence of restrictive airway disease (Smucny J et al 2004).

Whether it is treated or not, acute bronchitis will typically resolve on its own as the inflammation of the bronchi gradually subsides and the airways open again. Nevertheless, the condition is aggravating and painful while it persists, so early intervention—at the first sign of symptoms of viral infection—is important to prevent acute bronchitis. More information on Life Extension’s aggressive early intervention programs for the common cold and influenza can be found elsewhere in this book. Life Extension also advocates that people practice good “viral hygiene” by washing their hands as frequently as possible and avoiding coming into close contact with infected people.

Antioxidant Therapy

Antioxidants, which combat free radicals and reduce oxidative stress, are important weapons in the fight against respiratory infections. During an infection, the immune system is activated into producing inflammatory cytokines and increasing free radical production (Biesalski HK et al 1995). The oxidative stress caused by increased free radical production enhances the inflammation already present, leading to a self-reinforcing cycle of inflammation and free radical production.

Vitamin C. Although few clinical trials have addressed antioxidants and acute bronchitis, it is logical that people suffering from inflammation of the bronchi and elevated free radical damage would benefit from a strong antioxidant defense. There is also good evidence that large doses of vitamin C can interfere with viral infections at the first sign of symptoms (Gorton HC et al 1999), thus reducing one’s risk of developing acute bronchitis.

a)In one study, investigators examined cold and flu symptoms in two groups of students. Individuals in the control group were given conventional pain relievers and decongestants, whereas those in the test group were treated with hourly doses of 1000 mg vitamin C for the first six hours and then three times a day thereafter. Flu and cold symptoms in the test group decreased 85 percent compared with the control group (Gorton HC et al 1999).

b)In a randomized, double-blind study, older patients hospitalized with acute respiratory infections (bronchitis and bronchopneumonia) were given 200 mg vitamin C daily. On evaluation two and four weeks after admission, significant increases in vitamin C concentration in plasma and white cells were noted, even in the presence of acute respiratory infection. Patients were further evaluated by a clinical scoring system based on primary symptoms of their respiratory illness. Those receiving vitamin C fared significantly better than those who received placebo (Hunt C et al 1994).

Vitamin E. Evidence from animal and human studies also shows that vitamin E, a powerful antioxidant, plays an important role in the maintenance of the immune system. Even marginal deficiencies in vitamin E may predispose individuals to viral infections by reducing the immune response. Therefore, supplying the body with additional antioxidants could reduce oxidative stress and enhance immune function (Beharka A et al 1997). A recent review has proposed that supplementation with antioxidants may improve or exert a protective effect on lung health (Romieu I 2005).

N-acetylcysteine. N-acetylcysteine (NAC) is a precursor of glutathione, an important internal antioxidant. NAC has been in clinical use for more than 30 years as a mucolytic drug. NAC is routinely used to boost antioxidant levels and dissolve mucus in people suffering from respiratory ailments (Kupczyk M et al 2002).

In a randomized study of 24 bronchitis patients with an average age of 66, the addition of 600 mg NAC twice daily to standard therapy improved symptoms and quality of life (Reichenberger F et al 2002). Other investigators have shown that administration of NAC reduces episodes of influenza and influenza-like illnesses, especially in older high-risk individuals (De Flora A et al 1997).

Inflammation and Additional Nutrient Support

Omega-3 fatty acids. The defining feature of acute bronchitis is inflammation that produces symptoms. Fortunately, many nutrients have been shown to reduce inflammation by interfering with the cascade of chemical reactions that causes inflammation. Among the best known are the omega-3 fatty acids. These essential fatty acids have been shown to decrease the production of bronchorestrictive leukotrienes by reducing the production of arachidonic acid. Some researchers believe that this effect explains why Eskimos, who eat a lot of these fatty acids in a diet rich in cold-water fish, experience less lung disease than other populations (Schwartz J 2000).

Curcumin. Curcumin, which is derived from the common spice turmeric, is also a natural anti-inflammatory. This supplement is a natural inhibitor of nuclear factor kappa beta, which mediates most inflammatory processes in the body. Curcumin has shown promise in protecting lung tissue against inflammation induced by chemical and infectious agents in the laboratory (Venkatesan N 2000). Although there are no human trials examining curcumin in acute bronchitis, its antioxidant and anti-inflammatory properties make it a logical therapy.

Bromelain. Bromelain, an extract of the pineapple plant, has also demonstrated anti-inflammatory and mucolytic properties (Maurer HR 2001). Bromelain is a collective term for enzymes found in pineapple fruit, stem, and leaves. These enzymes are proteolytic, meaning they break down protein into its constituent peptides and amino acids. Bromelain has been found to be a mucolytic, or a compound that breaks down mucus (Bernkop-Schnurch A et al 2000). A recent review also noted that bromelain may offer therapeutic benefits to individuals who have bronchitis and sinusitis (Maurer HR 2001).

Life Extension’s Flu and Common Cold Program

Because acute bronchitis is so often caused by the flu virus and the common cold, a summary of Life Extension’s flu and common cold prevention program is presented here. For a more complete description, please see the appropriate chapters. At the first sign of infection, consider taking the following supplements. This program is not meant for long-term consumption because of the high doses. Follow these recommendations for only a few days.

Vitamin C. Megadoses of vitamin C (1000 mg every hour for the first 6 hours and three times daily thereafter) administered during or after influenza infection decreased influenza symptoms in a large group of students (Gorton HC et al 1999).

Vitamin E. Both human and animal studies have shown that vitamin E can help fight influenza infection by boosting the immune system (Hara M et al 2005; Gay R et al 2004). Animal studies have shown that vitamin E, in conjunction with other antioxidants, can help protect against the flu by reducing the oxidative damage associated with the virus:

After being infected with the influenza virus, aged mice fed a diet supplemented with vitamin E had significantly lower pulmonary viral levels and maintained their body weight, unlike control mice or mice fed with other antioxidants. Levels of pro-inflammatory cytokines, including interleukin-6 and tumor necrosis factor-alpha, were lowest in the group supplemented with vitamin E (Han SN et al 2000).
Vitamin E was shown to reduce the viral activity in the lungs of middle-aged mice after exposure to influenza (Meydani M 1999).
Supplementation with vitamin E before infection helped protect the lungs of the mice against lipid peroxidation (Mileva M et al 2002).

Selenium and zinc. A combination supplement containing selenium and zinc can reduce the severity of flu infection.

1)In one study, seniors who received an experimental formula of zinc, selenium, fermentable oligosaccharides (a kind of sugar that enhances beneficial bacteria), and structured triacylglycerides for 183 days showed signs of enhanced immune function and had fewer days of upper respiratory symptoms (Langkamp-Henken B et al 2004).

2)A two-year supplementation program of vitamins and micronutrients showed that selenium and zinc significantly reduced infections in elderly residents of nursing homes (Girodon F et al 1997) and enhanced the residents’ immune response to influenza vaccination (Girodon F et al 1999).
Mice that are deficient in selenium are more susceptible to influenza infection (Beck MA 2001). In selenium-deficient mice, the pro-inflammatory response is stronger and the immune response is weaker than in mice that have an adequate level of selenium (Beck MA et al 2003). Moreover, the genome of viruses in selenium-deficient mice shifts toward more virulent, resistant strains (Beck MA et al 2004).

Zinc has also been studied extensively for its ability to inhibit the viruses (such as the rhinovirus) that cause the common cold (Hulisz D 2004; Prasad AS et al 2000; Marshall S 1998; Mossad SB et al 1996).

Lactoferrin. Lactoferrin is a subfraction of whey and has antiviral, antimicrobial, anticancer, and immune-enhancing effects. Lactoferrin is concentrated in the saliva, where it comes into direct contact with pathogens and kills or suppresses them through a variety of mechanisms (Kawasaki Y et al 1993; Schoen P et al 1997). Lactoferrin may stimulate macrophages, which in turn may help induce cell-mediated immunity (Zimecki M et al 2002). Lactoferrin is present naturally in many mucous membrane secretions, suggesting an innate antimicrobial function (Zimecki M et al 2002; Nishiya K et al 1982). A recent study showed that lactoferrin inhibits viral infection by interfering with the ability of certain viruses to bind to cell receptor sites (Waarts BL et al 2005).

Elderberry extract. Studies show that a black elderberry extract (Sambucol) has antiviral properties against 10 strains of influenza virus. In a double-blind, placebo-controlled, randomized study, elderberry extract reduced the duration of influenza symptoms by one to two days (Barak V et al 2001; Zakay-Rones Z et al 1995).

Tea. Green tea has been shown to inhibit bacteria and viruses and stimulate the immune system. Black tea and extracted components, such as catechin and saponins (Hayashi K et al 2000), inhibit influenza virus growth, infectivity, and symptoms (Iwata M et al 1997a,b). In a cell culture study, the active ingredients in green tea were found to be powerful inhibitors of all varieties of influenza virus (Song JM et al 2005).

Garlic.

Garlic has been valued for centuries for its medicinal properties. Garlic, and its active component, allicin, have a wide spectrum of antifungal, antibacterial, and antiviral action. It benefits the immune system by increasing the number of natural killer cells and the killer activities of spleen cells (Harris JC et al 2001; Kyo E et al 2001). One recent study tested an allicin-containing garlic supplement on a group of 146 volunteers for four months. Half the group took one garlic capsule daily while the other half received a placebo. The placebo group had 63 percent more infections than the group that took the garlic capsule. Even more significant, those who took garlic capsules and who did catch a cold experienced symptoms for an average of only 1.52 days, compared with 5.01 days for the placebo group (Josling P 2001). Aged garlic has also been shown to have antiviral properties, particularly against influenza B (Tsai Y et al 1985) and to have immunomodulatory effects (Kyo E et al 2001).

Dehydroepiandrosterone and melatonin. In addition, the hormones dehydroepiandrosterone (DHEA) and melatonin have been shown to bolster the body’s immune response (Maestroni GJ 1993, 1999; Padgett DA et al 1997, 2000). Taking higher-than-usual doses (200 to 400 mg) of DHEA in the morning and higher-than-usual doses (10 to 50 mg) of melatonin before bedtime would appear to be logical approaches to battling a viral infection.

Cimetidine. The antiviral drug cimetidine (Tagamet®) is an over-the-counter drug used to treat heartburn. It also has potent immune system-boosting effects that can drastically reduce the duration of certain viral infections. Because cimetidine is safe for most people to take, 800 to 1000 mg taken at night (or 200 mg three times a day and 400 mg at night) can help boost the immune system in the event of exposure to influenza. Cimetidine in 200-mg tablets can be purchased over the counter. The directions in over-the-counter package inserts indicate that it is safe to take as much as 800 mg cimetidine a day. Some published studies state that up to 1000 mg cimetidine daily is safe (Choi YS et al 1993).

Life Extension Foundation Recommendations

By staying healthy and avoiding viral infection and environmental pollutants whenever possible, your chances of contracting acute bronchitis will be greatly reduced. Acute bronchitis is more common during the winter months, the flu and cold season, than at other times. Common-sense strategies to prevent acute bronchitis include ensuring appropriate and thorough hand washing to avoid exposure to viruses and reducing exposure to such irritants as air pollution, tobacco, and smoke (Hueston WJ et al 1998).

If exposure to a potential virus has already occurred, Life Extension’s aggressive anticold and antiflu program may help reduce the risk of infection. At the first sign of infection, the following supplements may help ward off more serious illness:

1)Cimetidine—800 to 1000 milligrams (mg) daily

2)Pure Gar brand garlic—9000 mg once or twice daily (consume food after ingesting this amount of garlic to reduce esophageal burning)

3)Kyolic aged garlic extract—3600 mg daily

4)DHEA—200 to 400 mg daily in the morning

5)Lactoferrin—1200 mg daily

6)Zinc—two 24-mg lozenges every two hours while awake. This is a very high dosage of zinc and is toxic if taken for long periods. Take this much zinc only for a few days.

7)Melatonin—10 to 50 mg at bedtime

8)Vitamin C—6000 mg daily (1000 mg every hour for the first six hours), then 3000 mg daily (1000 mg several hours apart).

9)Vitamin E—400 international units (IU) daily

10)Green tea—725 mg daily. A decaffeinated form is available for people who are sensitive to caffeine.

11)Selenium—200 micrograms (mcg) daily

12)Elderberry extract—30 mg, three times daily

Once acute bronchitis has developed, the following nutrients might help reduce inflammation and provide your body with valuable antioxidant support:

13)Vitamin C—2000 to 3000 mg daily

14)Vitamin E—400 IU daily, with at least 200 mg gamma tocopherol

15)NAC—600 to 1800 mg daily

16)EPA/DHA—1400 mg EPA and 1000 mg DHA daily

17)GLA—900 to 1800 mg daily

18)Curcumin—800 to 1600 mg daily

19)Bromelain—500 mg daily, with food


Product Availability
All the nutrients and supplements discussed in this section are available through the Life Extension Foundation Buyers Club, Inc.

The blood tests discussed in this section are available through Life Extension National Diagnostics, Inc.

Bronchitis Safety Caveats
An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

Bromelain

1)Consult your doctor before taking bromelain if you are taking anticoagulants or antithrombotic agents. Bromelain can thin the blood.

2)Bromelain can cause gastrointestinal symptoms such as nausea and diarrhea.

3)Bromelain can cause bleeding from the uterus between menstrual periods (metrorrhagia) and excessive uterine bleeding during menstruation (menorrhagia).

Curcumin

1)Do not take curcumin if you have a bile duct obstruction or a history of gallstones. Taking curcumin can stimulate bile production.

2)Consult your doctor before taking curcumin if you have gastroesophageal reflux disease (GERD) or a history of peptic ulcer disease.

3)Consult your doctor before taking curcumin if you take warfarin or antiplatelet drugs. Curcumin can have antithrombotic activity.

4)Always take curcumin with food. Curcumin may cause gastric irritation, ulceration, gastritis, and peptic ulcer disease if taken on an empty stomach.

5)Curcumin can cause gastrointestinal symptoms such as nausea and diarrhea.

DHEA

1)Do not take DHEA if you could be pregnant, are breastfeeding, or could have prostate, breast, uterine, or ovarian cancer.

2)DHEA can cause androgenic effects in woman such as acne, deepening of the voice, facial hair growth and hair loss.

EPA/DHA

1)Consult your doctor before taking EPA/DHA if you take warfarin (Coumadin). Taking EPA/DHA with warfarin may increase the risk of bleeding.

2)Discontinue using EPA/DHA 2 weeks before any surgical procedure.

Garlic

1)Garlic has blood-thinning, anticlotting properties.

2)Discontinue using garlic before any surgical procedure.

3)Garlic can cause headache, muscle pain, fatigue, vertigo, watery eyes, asthma, and gastrointestinal symptoms such as nausea and diarrhea.

4)Ingesting large amounts of garlic can cause bad breath and body odor.

GLA

1)Consult your doctor before taking GLA if you take warfarin (Coumadin). Taking GLA with warfarin may increase the risk of bleeding.

2)Discontinue using GLA 2 weeks before any surgical procedure.
GLA can cause gastrointestinal symptoms such as nausea and diarrhea.

Green Tea

1)Consult your doctor before taking green tea extract if you take aspirin or warfarin (Coumadin). Taking green tea extract and aspirin or warfarin can increase the risk of bleeding.

2)Discontinue using green tea extract 2 weeks before any surgical procedure. Green tea extract may decrease platelet aggregation.

3)Green tea extract contains caffeine, which may produce a variety of symptoms including restlessness, nausea, headache, muscle tension, sleep disturbances, and rapid heartbeat.

Melatonin

1)Do not take melatonin if you are depressed.

2)Do not take high doses of melatonin if you are trying to conceive. High doses of melatonin have been shown to inhibit ovulation.

3)Melatonin can cause morning grogginess, a feeling of having a hangover or a “heavy head,” or gastrointestinal symptoms such as nausea and diarrhea.

NAC

1)NAC clearance is reduced in people who have chronic liver disease.

2)Do not take NAC if you have a history of kidney stones (particularly cystine stones).

3)NAC can produce a false-positive result in the nitroprusside test for ketone bodies used to detect diabetes.

4)Consult your doctor before taking NAC if you have a history of peptic ulcer disease. Mucolytic agents may disrupt the gastric mucosal barrier.

5)NAC can cause headache (especially when used along with nitrates) and gastrointestinal symptoms such as nausea and diarrhea.

Selenium

1)High doses of selenium (1000 micrograms or more daily) for prolonged periods may cause adverse reactions.

2)High doses of selenium taken for prolonged periods may cause chronic selenium poisoning. Symptoms include loss of hair and nails or brittle hair and nails.

3)Selenium can cause rash, breath that smells like garlic, fatigue, irritability, and nausea and vomiting.

Vitamin C

1)Do not take vitamin C if you have a history of kidney stones or of kidney insufficiency (defined as having a serum creatine level greater than 2 milligrams per deciliter and/or a creatinine clearance less than 30 milliliters per minute.

2)Consult your doctor before taking large amounts of vitamin C if you have hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia, or erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. You can experience iron overload if you have one of these conditions and use large amounts of vitamin C.

Vitamin E

1)Consult your doctor before taking vitamin E if you take warfarin (Coumadin).

2)Consult your doctor before taking high doses of vitamin E if you have a vitamin K deficiency or a history of liver failure.

3)Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia.

4)Discontinue using vitamin E 1 month before any surgical procedure.

Zinc

1)High doses of zinc (above 30 milligrams daily) can cause adverse reactions.

2)Zinc can cause a metallic taste, headache, drowsiness, and gastrointestinal symptoms such as nausea and diarrhea.

3)High doses of zinc can lead to copper deficiency and hypochromic microcytic anemia secondary to zinc-induced copper deficiency.

4)High doses of zinc may suppress the immune system.

RESPIRATORY-CHRONIC OBSTRUCTIVE PULMONARyY DISEASE

Emphysema and Chronic Bronchitis


Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating lung disease. The disease is characterized by irreversible airflow limitation in the lungs. The umbrella of COPD encompasses the following conditions:

1)Emphysema, in which the alveoli in the lungs, the tiny sacs where oxygen transfer takes place, are destroyed and enlarged

2)Chronic bronchitis, or the permanent inflammation of airways, accompanied by a chronic cough
COPD exacts a tremendous toll on society. It affects more than 16 million people in the United States, and by 2020 it is expected to rise from the sixth- to the third-most-common cause of death in the world (Kasper DL et al 2005). Unfortunately, there is no single safe and effective treatment. However, because COPD is an inflammatory disease in which sufferers are subjected to high levels of oxidative stress, high doses of antioxidants and natural anti-inflammatories may be able to slow the disease’s progression and reduce the amount of prescription medication needed.

Inflammation and Airway Restriction

The major cause of COPD in the United States is cigarette smoking, although it has also been linked to other factors, such as hyperresponsive airways, respiratory infections, and exposure to dust and environmental pollutants. The longer and more heavily people smoke, the more likely they are to develop COPD.

COPD is usually a progressive disease that develops slowly, often over the course of decades. In a typical case, a cigarette smoker would experience declining lung function for many years before being diagnosed with COPD and receiving therapy. During those years, while the disease is developing, the lungs are undergoing several changes characteristic of the disease.

The bulk of lung tissue is composed of alveoli, or tiny sacs, where the exchange of oxygen and carbon dioxide takes place. One of the primary factors in COPD is emphysema, which occurs when alveoli enlarge and cluster. This process destroys the very sensitive areas where gases are exchanged across thin walls. Emphysema occurs in stages. First, chronic exposure to an irritant, such as cigarette smoke, causes inflammatory cells (such as macrophages and neutrophils) to gather in the airspaces of the lung. These inflammatory cells release chemicals that damage the extracellular matrix of the lung, that is, the proteins that are responsible for providing structure to the lungs. Finally, the ability of the lung to repair the extracellular matrix is compromised, resulting in the coalescence of alveoli into larger, less efficient air chambers.

People with emphysema also suffer from airway obstruction, especially in airways less than 2 mm in diameter. A number of changes occur in these airways that aggravate the disease, including hypertrophy of smooth muscle cells, the formation of scar tissue in the airway walls (fibrosis), and the infiltration of inflammatory cells.

Underlying all this damage is an inflammatory response mounted by the immune system. In a typical case, cigarette smoke in the lungs would come into contact with macrophages (immune system cells) that normally patrol the airspace. In response to the toxins in the smoke, the macrophages release inflammatory chemicals and begin to recruit more immune-system cells, which in turn release more inflammatory chemicals, as well as enzymes that degrade the extracellular matrix.

These changes in the lung are detectable but incremental. Symptoms appear gradually and may actually have been present for many years before a patient seeks medical treatment. Coughing, sputum production, and breathlessness are the characteristic symptoms associated with COPD. Early in the disease, the patient’s physical examination may even be normal. Later in the disease, however, patients sometimes develop the classic “barrel chest” associated with COPD. It occurs because residual air is trapped in the lungs, leading to their hyperinflation. In addition, the increased effort required to exhale can produce wheezing, while pursed lips or grunting respirations may signal the patient’s efforts to keep the airways open by increasing pressure at the beginning of expiration (Lim TK 1996).

COPD is a variable condition, with some patients having more symptoms of emphysema, such as breathlessness and “air hunger,” while others manifest more symptoms of chronic bronchitis or asthma, such as wheezing and air trapping (Kasper DL et al 2005). The manifestations of COPD are not limited to the lungs. COPD also puts patients at increased risk of atherosclerosis and osteoporosis. Poor lung function and poor nutrition may cause muscle weakness, abnormalities in fluid and electrolyte balance, and depression.

Genetic Causes of COPD

Although cigarette smoking is the major risk factor for COPD, in recent years researchers have uncovered genetic abnormalities that may make people more susceptible to the disease. Hereditary deficiency of an enzyme called alpha-1 antitrypsin confers significant increased risk (Kasper DL et al 2005). Unlike other forms of COPD, lung damage in alpha-1 antitrypsin deficiency appears relatively early in life (Lee P et al 2002). Patients with alpha-1 antitrypsin deficiency also may have liver disease and other organ system damage, and they are more vulnerable to the damaging effects of cigarette smoke (US National Library of Medicine 2005).

Variations in other genes may explain some of the variability in severity and age at onset of COPD, and researchers hope to identify markers of these genes that will permit early identification of people at the greatest risk (US National Library of Medicine 2005; Meyers DA et al 2004).

Diagnosis and Conventional Treatment

COPD should be considered in any individual with a chronic cough, sputum production, shortness of breath, or risk factors such as tobacco use, alpha-1 antitrypsin deficiency, or occupational exposure to dust and chemicals. Diagnostic testing should include pulmonary function tests (PFTs). PFTs determine lung volume and capacity and take dynamic measurements, such as the amount of air the patient can force out of the lungs during a given time interval. The results of PFTs are used to determine the severity of COPD, which in turn can establish the likely prognosis and may help guide treatment (Pierson DJ 2006). Other tests, such as x-rays, computed tomography, and magnetic resonance imaging, may be performed if complications such as pneumonia are suspected.

COPD cannot be cured, in part because it usually is the result of years of development. According to the Global Initiative for Chronic Obstructive Lung Disease, effective COPD management has the following goals (Global Strategy 2004):

1)Preventing disease progression

2)Relieving symptoms

3)Improving exercise tolerance and health status

4)Preventing and treating complications and exacerbations

5)Reducing mortality

Among the most important steps for smokers is to quit smoking immediately. Studies have shown that if smoking is ceased early in the disease, the rate of lung decline might be slowed to that of a normal nonsmoker (Kasper DL et al 2005).

Bronchodilators are first-line therapy for COPD (Sutherland ER 2004). This large group of drugs includes the following (Weder MM 2005):

1)Beta agonists, or agents derived from adrenaline (such as albuterol)

2)Anticholinergics, or agents related to atropine (such as ipratropium)

3)Methylxanthines, or agents related to caffeine (such as theophylline)

All three categories have some effectiveness, but all three also produce significant side effects, such as increased heart rate and blood pressure, trembling, and cardiac arrhythmias. The anticholinergics, particularly some of the more recent long-acting agents such as tiotropium, may provide the best combination of tolerability and duration of action (Koumis T 2005). Side effects of these drugs include chest pain, blurred vision, and more. Theophylline has fallen out of use in the industrialized world because of better alternatives, but its low cost and wide availability make it a still-useful agent in less-developed countries (Weder MM 2005).

Patients who cannot be maintained on bronchodilators may need to start an inhaled steroid medication. At low doses, these medications are safe, and they have been shown to contribute to an improvement in quality of life for patients suffering from COPD (Calverley PM 2004).

When COPD patients experience an exacerbation of their disease, more aggressive medical therapy may be required. The most commonly used medications in this situation are the short-acting bronchodilators, which are sometimes used on an as-needed basis to relieve acute symptoms (Chorostowska-Wynimko J 2005; Urbano FL 2005). Inhaled and occasionally oral steroid medications may be added as well. If the acute exacerbation is caused by a bacterial infection, antibiotics may be prescribed.

The most severe exacerbations of COPD require hospitalization, often with mechanical ventilation in an intensive care unit. Unfortunately, ventilatory management of COPD patients is complex and has many pitfalls. This has led to increased use of home, noninvasive, positive-pressure ventilation systems that may stave off the need for more-aggressive treatment (Brochard L 2003; Wijkstra PJ 2003).

New drugs. About 70 therapeutic drugs are in development for related COPD needs. The newest class of drugs is phosphodiesterase-4 inhibitors; two of these, roflumilast and cilomilast, may be available in the near future (Business Wire 2004). Phosphodiesterase-4 inhibitors produce bronchial smooth muscle relaxation by taking away the intracellular stimulus that maintains contraction. This effect is similar to that of the other bronchodilators, though it is produced by a different and more targeted mechanism and produces fewer side effects. These drugs have been shown to reduce inflammation, improve lung function, decrease exacerbations, and improve quality of life (Vignola AM 2004).

Researchers are also reporting amazing results with retinoic acid, a biologically active form of vitamin A. In a mouse model of emphysema, retinoic acid was able to completely restore lung architecture and alveolar function (Hind M et al 2004; Maden M et al 2004). Human studies have been similarly encouraging. In one randomized, double-blind, placebo-controlled study, all-trans-retinoic acid was administered in low doses to 20 patients with severe emphysema. The drug was well tolerated, with few side effects, and the researchers called for longer studies with higher doses (Mao JT et al 2002). The same group of investigators also found that retinoic acid restores the balance of important enzymes called matrix metalloproteinases that are thought to contribute to alveolar breakdown (Mao JT et al 2003).

Flu vaccines. Flu vaccines can reduce COPD exacerbations, serious illness, and death by 50 percent. They are given in the fall or twice a year, in fall and winter. Vaccines that prevent infection with the bacterial organism pneumococcus can reduce complications such as pneumonia and may reduce the rate of exacerbations of the disease. (Alfageme I et al 2006; Ansaldi F et al 2005).

Nutritional Therapy

Medications and surgery can be effective in treating symptoms, but they do little to prevent disease progression. Mortality rates from COPD are still high, and quality of life is often severely impaired.

Nutritional supplementation aimed at increasing antioxidant capacity and reducing inflammation may offer significant added value (Schols A 2003; Romieu I et al 2001). In addition, people with COPD have increased energy requirements because it is harder for them to breathe. Difficulty breathing may affect eating, potentially resulting in malnutrition. Proper nutrition through a balanced diet and appropriate supplementation is important in COPD management.

Because of the role of oxidant stress in causing and perpetuating COPD (Drost EM et al 2005) and the low levels of natural antioxidants in patients’ tissues (Kluchova Z et al 2006; Rahman I et al 2006; Nadeem A et al 2005), antioxidant supplementation may be helpful (Kelly FJ 2005; Spurzem JR et al 2005; Romieu I et al 2001).

Vitamins A, C, and E. Levels of vitamins A and E are significantly lower during exacerbations of COPD than they are in stable COPD, suggesting that antioxidants should be used during exacerbations (Tug T et al 2005). Although vitamins A, C, and E are beneficial, vitamin A may be most important because it catalyzes removal of the most reactive form of oxygen radical (Tug T et al 2005). Serum levels of vitamin A are lower in those with moderate or severe COPD. Vitamin A supplements for 30 days improved performance on PFTs in one small study (Paiva SA et al 1996).

Vitamin E levels are low in smokers, increasing their susceptibility to injury from free radicals. Vitamin E supplementation can reduce the risk of COPD in smokers (Daga MK et al 2003). Serum vitamin C levels are also frequently reduced in COPD (Tug T et al 2005). High-dose vitamin C may prevent oxidant-mediated lung injury during inflammation. Vitamin C also reactivates vitamin E that has been depleted by oxidant molecules.

Coenzyme Q10. When coenzyme Q10 (CoQ10) was given to eight COPD patients with low levels of the nutrient, they experienced improved oxygenation of blood without a change in lung function. Oxygen pressure significantly improves, and heart rate decreases. Exercise performance increases. CoQ10 affects muscular energy metabolism in chronic lung diseases (Fujimoto S et al 1993).

N-acetylcysteine. N-acetylcysteine (NAC) is a powerful antioxidant that protects against toxins, including acrolein, found in cigarette smoke. NAC is a selective immune-system enhancer, improving symptoms by breaking down mucus and preventing recurrence of lung illness such as chronic bronchitis. Supplementation with NAC reduces exacerbation and improves chronic bronchitis (Stey C et al 2000).

L-carnitine. Respiratory infections increase the frequency and severity of exacerbations. L-carnitine may boost immune function, enhance fatty acid and glucose energy metabolism, and prevent wasting syndrome. In one very recent human trial, carnitine improved exercise tolerance and the strength of respiratory muscles in COPD patients; levels of the metabolic by-product lactate, which causes fatigue, were also reduced (Borghi-Silva A et al 2006).

Bromelain. Bromelain, which is present in the pineapple fruit, can benefit stable COPD patients and decrease exacerbations by reducing mucus production (Bernkop-Schnurch A et al 2000). Individuals allergic to pineapple may be sensitive to bromelain. Gastritis can be aggravated by bromelain (Jaber R et al 2002).

Essential Fatty Acids
Essential fatty acids are those that cannot be produced by the body and must come from dietary or supplemental sources. Omega-3 fatty acids are essential in modulating toxic inflammatory responses. Omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) protect against damaging inflammatory reactions and, with vitamin E, build healthy cell membranes and repair tissues (Ergas D et al 2002; Fernandes G et al 1996).

The destructive effects of chronic inflammation on cellular structures can be reduced by supplementing with EPA and DHA, which repair both cell and mitochondrial membranes (Chapkin RS et al 2002). Mitochondrial membranes, because of their involvement in energy production, are especially susceptible to oxidant damage.

Supplementing with omega-3 fatty acids improves oxygen transfer in adult respiratory distress syndrome, a condition in which oxidant damage and inflammation cause impaired lung function. Omega-3 supplements have been shown to be beneficial in patients with COPD. One study showed a significant improvement in dyspnea and pulse oximetry levels and a decrease in inflammatory markers in serum and sputum in a group of patients receiving supplementation, compared with controls (Matsuyama W et al 2005). Higher dietary levels of omega-3 fatty acids may protect smokers against COPD (Shahar E et al 1994).

Nondrug Strategies

Smoking cessation and patient education. The major cause of COPD is cigarette smoking. Comprehensive smoking cessation programs include counseling, organized “quit” plans, and when necessary, nicotine replacement therapy (such as gum, inhalers, skin patches, and other methods). Drugs such as bupropion (Wellbutrin®) are also effective when taken under a doctor’s care (Cornuz J 2006). Both hypnosis and acupuncture may be helpful in quitting smoking (Zwick H 2005). The National Network of Tobacco Cessation Quitlines at 1-800-QUITNOW (1-800-784-8669) can provide information on finding a quitline in any geographical area in the United States.

Exercise programs. Because air passage is obstructed in COPD, the lungs and heart work harder to carry oxygen throughout the body. Exercise programs strengthen chest muscles and facilitate breathing. Multidisciplinary pulmonary rehabilitation programs provide well-monitored exercise programs.

Breathing exercises. Breathing exercises induce relaxation and make breathing easier. Pursed-lip breathing stimulates relaxation, increasing oxygen intake and preventing shortness of breath. It has been shown to increase exercise tolerance and shorten recovery times (Garrod R et al 2005). Breathing exercise regimens are an important part of a COPD rehabilitation program. Respiratory therapists working closely with physicians can specify the best regimen for each individual (Beckerman M et al 2005).

Oxygen. Oxygen therapy alleviates a lack of oxygen but increases oxidative stress, potentially increasing damage to airways. Patients with COPD are known to have reduced antioxidant capacity (Kluchova Z et al 2006; Rahman I et al 2006), which may be further diminished by oxygen therapy (Nadeem A et al 2005). A recent study, however, demonstrated that supplemental oxygen actually reduced levels of oxidant molecules and inflammatory cytokines in exercising patients with COPD, presumably by supporting normal metabolism and preventing stress-induced oxidant species from being produced (van Helvoort HA et al 2006).

Surgery. Surgical interventions are becoming more important in COPD as techniques improve (Kasper DL et al 2005). When alveoli coalesce in emphysema, they can form large blebs, or bullae; surgical removal of these bullae can help restore lung volume and allow remaining healthy parts of the lung to function better. Similarly, lung volume reduction surgery has been used successfully to improve lung function and quality of life. Lung transplantation is also a consideration for COPD sufferers.

Life Extension Foundation Recommendations
Any patients with COPD, emphysema, or bronchitis are urged to stop smoking and to limit their exposure to environmental toxins whenever practical. Additionally, exercise, breathing exercises, and oxygen therapy may be helpful, as well as the use of steam and hot-mist vaporizers. If the breathing difficulty results in trouble eating, a strong multivitamin that includes magnesium is recommended to prevent malnutrition and restore energy to damaged cells.

Studies have shown that retinoic acid has a remarkable ability to restore alveolar architecture. Retinoic acid is available as Vesanoid (tretinoin) for the treatment of leukemia, but it can be prescribed for COPD.

In addition, the following nutrients have been shown to restore antioxidant capacity and help reduce inflammation:

1)Vitamin A—25,000 international units (IU) daily

2)Vitamin C—3000 milligrams (mg) daily

3)Vitamin E—400 IU daily (with at least 200 mg gamma tocopherol)

4)NAC—600 mg, three times daily

5)CoQ10—200 to 400 mg daily

6)Omega-3 fatty acids—1000 mg DHA and 1400 mg EPA daily

7)Gamma-linolenic acid—900 to 1800 mg daily

8)Acetyl-L-carnitine—2000 to 3000 mg daily

9)Bromelain—500 mg at the beginning of each meal


Product Availability
All the nutrients and supplements discussed in this section are available through the Life Extension Foundation Buyers Club, Inc.

The blood tests discussed in this section are available through Life Extension National Diagnostics, Inc. ORDER ON LINE
COPD Safety Caveats

An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

Acetyl-L-Carnitine

1)Acetyl-L-carnitine can cause gastrointestinal symptoms such as nausea and diarrhea.

Bromelain

1)Consult your doctor before taking bromelain if you are taking anticoagulants or antithrombotic agents. Bromelain can thin the blood.

2)Bromelain can cause gastrointestinal symptoms such as nausea and diarrhea.

3)Bromelain can cause bleeding from the uterus between menstrual periods (metrorrhagia) and excessive uterine bleeding during menstruation (menorrhagia).

Coenzyme Q10

1)See your doctor and monitor your blood glucose level frequently if you take CoQ10 and have diabetes. Several clinical reports suggest that taking CoQ10 may improve glycemic control and the function of beta cells in people who have type 2 diabetes.

2)Statin drugs (such as lovastatin, simvastatin, and pravastatin) are known to decrease CoQ10 level.

EPA/DHA

1)Consult your doctor before taking EPA/DHA if you take warfarin (Coumadin). Taking
2)EPA/DHA with warfarin may increase the risk of bleeding.

3)Discontinue using EPA/DHA 2 weeks before any surgical procedure.

GLA

1)Consult your doctor before taking GLA if you take warfarin (Coumadin). Taking GLA with warfarin may increase the risk of bleeding.

2)Discontinue using GLA 2 weeks before any surgical procedure.

3)GLA can cause gastrointestinal symptoms such as nausea and diarrhea.

NAC

1)NAC clearance is reduced in people who have chronic liver disease.

2)Do not take NAC if you have a history of kidney stones (particularly cystine stones).

3)NAC can produce a false-positive result in the nitroprusside test for ketone bodies used to detect diabetes.

4)Consult your doctor before taking NAC if you have a history of peptic ulcer disease. Mucolytic agents may disrupt the gastric mucosal barrier.

5)NAC can cause headache (especially when used along with nitrates) and gastrointestinal symptoms such as nausea and diarrhea.

Vitamin A

1)Do not take vitamin A if you have hypervitaminosis A.

2)Do not take vitamin A if you take retinoids or retinoid analogues (such as acitretin, all-trans-retinoic acid, bexarotene, etretinate, and isotretinoin). Vitamin A can add to the toxicity of these drugs.

3)Do not take large amounts of vitamin A. Taking large amounts of vitamin A may cause acute or chronic toxicity. Early signs and symptoms of chronic toxicity include dry, rough skin; cracked lips; sparse, coarse hair; and loss of hair from the eyebrows. Later signs and symptoms of toxicity include irritability, headache, pseudotumor cerebri (benign intracranial hypertension), elevated serum liver enzymes, reversible noncirrhotic portal high blood pressure, fibrosis and cirrhosis of the liver, and death from liver failure.

Vitamin C

1)Do not take vitamin C if you have a history of kidney stones or of kidney insufficiency (defined as having a serum creatine level greater than 2 milligrams per deciliter and/or a creatinine clearance less than 30 milliliters per minute.

2)Consult your doctor before taking large amounts of vitamin C if you have hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia, or erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. You can experience iron overload if you have one of these conditions and use large amounts of vitamin C.

Vitamin E

1)Consult your doctor before taking vitamin E if you take warfarin (Coumadin).

2)Consult your doctor before taking high doses of vitamin E if you have a vitamin K deficiency or a history of liver failure.

3)Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia.

4)Discontinue using vitamin E 1 month before any surgical procedure.

RESPIRATORY-SINUSITIS

Sinusitis

The sinuses are air-filled sacs in the facial bones of the head. They have several functions, including warming incoming air and helping to form certain sounds. When the sinuses become infected and inflamed, the condition is known as sinusitis. Sinusitis ranges from a minor annoyance to a serious condition that might require surgery.

The four pairs of sinuses are listed below, in order from highest frequency of infection to least:

1)Maxillary sinuses, located in the cheekbone, right below the eye sockets

2)Ethmoid sinuses, located behind the bridge of the nose

3)Frontal sinuses, located in the lower forehead, in the middle of the head just above the eye sockets

4)Sphenoid sinuses, located behind the eyes

The sinuses are lined with cells covered with small, hair-like projections called cilia, which help clear mucus from the chambers and keep them bacteria free (Rubin BK et al 2004). When the ability to clear the passageways is blocked, however, the sinuses may become infected. Sinusitis is classified by duration of illness (acute or chronic), by cause (infectious or other), and by the type of infectious agent involved (bacterial, fungal, or viral). According to the National Institutes for Health, approximately 37 million Americans are affected by sinusitis every year. Health care providers report nearly 32 million cases of chronic sinusitis every year (National Institute of Allergy and Infectious Diseases 2005).

Even if it is not considered serious, sinusitis can have a major impact on quality of life (Bhattacharyya N 2003; Chester AC 2003; Linder JA et al 2003). In rare cases, sinusitis can cause infections of the brain and other complications (National Institute of Allergy and Infectious Diseases 2005).

Researchers in Japan have found a link between chronic sinusitis in older people and cognitive impairment (Matsui T et al 2003). A study of an older population found significant differences in Mini-Mental Status Examination. Examination scores between people with chronic sinusitis and those without (Matsui T et al 2003) underscore the importance of treating sinusitis infections appropriately in this age group.

Causes and Risk Factors for Sinusitis
Acute sinusitis is almost always caused by bacteria, fungi, or viruses. Bacteria that cause sinusitis include streptococcal and staphylococcal strains, which also cause the common cold. Fungi are known to cause sinusitis, but mainly in immunocompromised people (such as those with HIV/AIDS) or people who are sensitive to fungi (Shin SH et al 2004; Parikh SL et al 2004). People at highest risk for sinusitis are those with allergies, asthma, or an increased immune response to fungi; smokers; or those with compromised immune systems (Kasper DL et al 2005).

Noninfectious risk factors for sinusitis include rapid changes in air pressure (e.g., when diving, flying, or high-altitude hiking) and exposure to chemical irritants (Rubin BK et al 2004; American Academy of Family Physicians 2005). Additional risk factors for sinusitis are conditions that cause sinus obstruction, such as tumors, and conditions that alter mucus clearance, such as cystic fibrosis (Rubin BK et al 2004).

Diagnosis of Sinusitis

No single test confirms a diagnosis of sinusitis. In most cases, the diagnosis will be made on the basis of symptoms, which depend on which sinus or sinuses are affected. Common symptoms include:

Headache

1)Pain in the forehead, over the area where the frontal sinuses are located

2)Upper jaw pain

3)Toothache

4)Pain in the eyes

5)Swelling of the eyelids or areas around the eyes

6)Earache

7)Neck pain

8)Tenderness on the sides of the nose

9)Loss of smell

10)Thick or colored nasal discharge

Conventional Treatment of Sinusitis

Decongestants. The major decongestants used in over-the-counter medications are phenylephrine and pseudoephedrine. Decongestants are usually coupled with a pain reliever, such as acetaminophen, ibuprofen, or aspirin. Over-the-counter medications are used to (1) reopen the nasal passages by reducing the volume of mucus, (2) reduce nasal congestion, (3) relieve pain and pressure, and (4) reduce the potential for complications.

Antibiotics. Antibiotics are used to treat bacterial sinusitis (Rubin BK et al 2004). In very serious cases, intravenous antibiotics may be recommended (Rubin BK et al 2004). They are ineffective in viral sinusitis.

Pain relievers. Pain relievers are often used in conjunction with decongestants. Acetaminophen, ibuprofen, and aspirin are all commonly used in sinusitis.

Corticosteroids. Steroids are used to suppress inflammation. They may be used in topical nasal sprays.

Nonpharmacological therapies. Sinusitis sufferers sometimes use the following therapies, sometimes in combination with pharmaceuticals.

1)Steam treatment

a)A warm, moist towel to the face

b)A humidifier

2)Nasal saline wash

a)If symptoms are mild to moderate, some healthcare providers will delay treatment with medications in favor of nasal saline solution. However, if symptoms continue for seven days or longer, more aggressive treatment is implemented.

3)Surgery

a)Surgical treatment to debride abscesses or to remove impacted mucus is used for very serious cases of sinusitis.

Nutrient and Supplemental Therapy
Because most cases of sinusitis are caused by bacterial or viral infection, such infections should be treated aggressively—at the first sign of infection—to prevent them from spreading into the sinuses. In addition to getting plenty of rest and drinking a lot of fluid, sufferers may take the following supplements, which have been shown to inhibit infection with viral or bacterial agents that cause the common cold and influenza:

Dehydroepiandrosterone (DHEA). Aging humans gradually lose youthful levels of DHEA, an adrenal hormone and precursor to other important hormones in the body (Shealy CN 1995). Numerous studies have shown that DHEA causes powerful immune-enhancing and antiviral effects (Ben-Yehuda A et al 1998; Corsini E et al 2002; Danenberg HD et al 1995, 1997; Degelau J et al 1997; Padgett DA et al 1997, 2000). The administration of 50 mg DHEA daily to older men resulted in the following immune enhancements compared to placebo :

1)35 percent increase in the number of monocyte immune cells

2)29 percent increase in the number of B immune cells

3)62 percent increase in B cell activity

4)40 percent increase in T cell activity

5)50 percent increase in interleukin (IL)-2

6)22 percent to 37 percent increase in natural killer (NK) cell number

7)45 percent increase in NK cell activity

One reason influenza can be so lethal to older people is that their immune systems are weak. A deficiency in DHEA appears to be partially responsible for the age-related decline in immune function (Fulop T Jr et al 1999; Khorram O et al 1997). One study showed that a metabolite of DHEA augmented activation of helper T cells and protected mice from a lethal influenza virus infection (Padgett DA et al 1997).

Lactoferrin. Lactoferrin has well-documented antiviral, antimicrobial, anticancer, and immune enhancing effects. Lactoferrin secretion is increased during sinusitis, leading researchers to conclude that it is a potent part of the body's natural defense mechanism against sinusitis.

Lactoferrin has been found to directly and indirectly inhibit viruses such as respiratory syncytial virus, human HIV, cytomegalovirus, and herpes simplex type I infection (Puddu P et al 1998; Superti F et al 1997; Harmsen MC et al 1995; Swart PJ et al 1996, 1998; Sano H et al 2003). Specifically, lactoferrin has been shown to increase NK cells (Yamauchi K et al 1998; Swart PJ et al 1998; Waarts BL et al 2005).

Lactoferrin may stimulate macrophages, which in turn may help to induce cell-mediated immunity. Although many of the studies of lactoferrin's functioning have involved animals, lactoferrin is naturally present in many mucous membrane secretions in people, suggesting an innate human antimicrobial function (Nishiya K et al 1982; Zimecki M et al 2002).

A recent study showed that human lactoferrin interferes with the ability of certain viruses to bind to cell receptor sites (Waarts BL et al 2005).

Melatonin. Melatonin, a hormone produced by the pineal gland, has immunity-enhancing benefits in addition to its well-known role as a sleep aid. Melatonin enhances the production of key immune system components, such as NK cells, IL-2, IL-4, IL-10, and gamma interferon (Lissoni P et al 1989, 1994, 1995; Maestroni GJ 1999; Bubenik GA et al 1998). Melatonin has been specifically shown to decrease viral load and prevent death in mice infected with certain viruses. One study of melatonin concluded, “The immunomodulatory, antioxidant, and neuroprotective effects of melatonin suggest that this indole must be considered as an additional therapeutic alternative to fight viral diseases” (Maestroni GJ 1999).

Another study reviewed animal research that examined the immune function benefits of melatonin and found that melatonin activated IL-2 and gamma interferon, the body's natural hormone-like agents that facilitate helper T cell production (Bonilla E et al 2004).

Garlic. With all the high-tech advances occurring in medicine, garlic might be expected to be a relic of the past. Yet the scientific literature documents that garlic has powerful effects against certain viruses.

For instance, one study tested one capsule daily of an allicin-containing garlic supplement (like Pure Gar) on a group of 146 volunteers (Josling P 2001). Over several months half the group received the garlic while the other half got a placebo. The placebo group had 63 percent more common cold infections than the garlic group. Even more significant, those in the garlic group who did catch a cold had symptoms for an average of only 1.52 days, compared with 5.01 days for the placebo group. The doctors who conducted this garlic study concluded, “An allicin-containing supplement can prevent attack by the common cold virus.”

Ribavirin is a prescription drug that has potent antiviral effects (Cattral MS et al 1996; Christie JM et al 1999; da Silva LC et al 2002; de Ledinghen V et al 2002; Di Bisceglie AM et al 1995; Fried MW et al 2002; Galban GE et al 2000; Kumada H 2002; Murphy ME et al 2000; Reichard O et al 1998; Schalm SW et al 1997a,b,1999; Schvarcz R et al 1995). Yet, a Chinese study has found that (at least in the test tube) garlic is more effective than ribavirin in inhibiting viruses that attack the intestinal tract (Luo R et al 2001). Since 1983 the Life Extension Foundation has recommended ribavirin to treat various viral infections, but in this particular study, garlic was shown to be superior.

A number of published studies indicate that both high-allicin garlic (such as Pure Gar) and aged garlic (such as Kyolic aged garlic) support healthy immune function while exerting antiviral effects (Guo NL et al 1993; Josling P 2001; Kyo E et al 2001; Liu ZF et al 2004; Moon DG et al 2000; Tsai Y et al 1985; Weber ND et al 1992). Garlic may be nature's most powerful weapon against certain viruses.

Essential fatty acids. Maintaining the proper ratio of omega-3 to omega-6 fatty acids can maximize the production of anti-inflammatory prostaglandins E1 and E3 while suppressing proinflammatory prostaglandin E2 and leukotriene B4. Most people consume too much omega-6 relative to omega-3 fatty acids. The main omega-3 fatty acids are docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). DHA and EPA exert anti-inflammatory and antithrombotic effects, partly by competing with pro-inflammatory chemicals (Calder PC 2005; Conner WE 2001). Studies suggest that fish oils reduce the production of pro-inflammatory cytokines such as interleukin-1 beta and tumor necrosis factor. Additionally, they can suppress B- and T-lymphocyte synthesis (Kelley DS et al 2000; Endres S et al 1993; Burns EA et al 2004).

Green tea. Green tea, which is rich in antioxidants, has demonstrated the ability to inhibit bacteria (Sakanaka S et al 2000; Stapleton PD et al 2004) and viruses (Song JM et al 2005) and has also been shown to have a protective effect on immune function (Yamamoto Y et al 2004).

Vitamin C. Vitamin C is a potent free radical scavenger and antioxidant derived from citrus fruits and green vegetables. It protects tissues from oxidative stress and enables the actions of vitamin E. Vitamin C in high doses may reduce symptoms associated with viruses and respiratory infections such as colds and flu, which are associated with sinusitis (Gorton HC et al 1999; Hemila H 2004). Multiple studies have found that high doses of vitamin C alleviate common cold and flu symptoms, indicating that the vitamin does indeed have physiologic effects on colds (Hemila H 1997, 2004; Gorton HC et al 1999). In a five-year clinical trial of 50 mg versus 500 mg vitamin C daily, the high-dose group reported fewer colds than the low-dose group (Sasazuki S et al 2005). From a meta-analysis of four double-blind, placebo-controlled trials, Linus Pauling found a 45 percent decrease in the incidence of colds when 1000 mg ascorbic acid (vitamin C) was used daily (Pauling L 1971). Some studies, however, show that vitamin C does not affect the frequency or duration of a common cold.

Zinc. Zinc supports the actions of antiseptic agents and kills microbes directly (Zeelie JJ et al 1998; Sheng J et al 2005). Zinc deficiency is closely associated with susceptibility to infection (Bogden 2004). A number of published studies show that, if zinc lozenges are taken within 24 hours of the onset of common cold symptoms, the severity and duration of cold miseries are significantly diminished (Hulisz D 2004; Prasad AS et al 2000; Marshall S 1998; Mossad SB et al 1996).

Rhinoviruses attach to specific cell receptor sites in sinus and throat tissues, become lodged in the nose and throat, and then replicate out of control. By binding to the same cell receptor sites as do cold viruses, zinc inhibits the ability of rhinoviruses to take hold in the body (Gwaltney JM 2002).

A meta-analysis of all the published literature on zinc lozenges was conducted in 2004 and concluded, “Clinical trial data support the value of zinc in reducing the duration and severity of symptoms of the common cold when administered within 24 hours of the onset of common cold symptoms. Additional clinical and laboratory evaluations are warranted to further define the role of ionic zinc for the prevention and treatment of the common cold and to elucidate the biochemical mechanisms through which zinc exerts its symptom-relieving effects” (Hulisz D 2004).

Patients seeking to relieve cold symptoms by means of zinc should suck on two 24-mg zinc lozenges at the very first symptom of a cold and take two more lozenges every two hours while awake. Once rhinoviruses bind to their receptor sites in the nasal tissues and begin replicating, zinc lozenges lose their efficacy. Considering how inexpensive zinc lozenges are, it makes sense to keep them on hand so that they are available immediately if cold symptoms appear.

One caveat is that chronic use of zinc in doses of more than 100 mg daily may suppress immune function (Chandra RK 1984). If someone takes two zinc lozenges every two hours over the course of a day, the total zinc intake could easily exceed 300 mg daily. This does not appear to be a problem in the short term. If your cold symptoms do not subside after a few days of taking zinc lozenges, it would be best to stop taking them. Remember that less than 100 mg zinc daily can improve immune function, but taking more than 100 mg daily concerns some doctors.

Propolis. Before the discovery of antibiotics, honey was used in the fight against bacteria. The antibacterial effects of this folk remedy have since been confirmed by scientific study ( Lusby PE et al 2005). In addition, in vitro and in vivo studies have shown that bee propolis has antiviral and anti-inflammatory properties and an inhibitory effect on the growth and adherence of streptococci bacteria (Cohen HA et al 2004; Duarte S et al 2003; Mirzoeva OK et al 1996; Serkedjieva J et al 1992; Szmeja Z et al 1989). One study demonstrated that propolis decreased the duration of the common cold to just a few days. This study showed that cold symptoms in the propolis treatment group improved 2.5 times faster than in the placebo group (Szmeja Z et al 1989).

Warning: Raw honey should NEVER be given to a child under one year of age because it presents a significant risk of potentially fatal botulism. This risk vanishes in older children and adults.

Beta-carotene and vitamin E. Beta-carotene has been shown to have a powerful effect in boosting NK cell activity in older men. In a controlled, double-blind study, the effects of 10 to 12 years of beta-carotene supplementation on NK cell activity were evaluated. Although no significant difference was seen in NK cell activity in the middle-aged groups, older men supplemented with beta-carotene had significantly greater NK cell activity than the control group of men of comparable age (Santos et al 1996).

The best-publicized study of the use of vitamin E to boost immune function appeared in 1997 (Meydani et al 1997). The double-blind, placebo-controlled study looked at healthy humans at least 65 years of age. Supplementation with vitamin E for four months improved certain clinically relevant indices of cell-mediated immunity. These results show that a level of vitamin greater than that currently recommended by the Food and Drug Administration enhances certain clinically relevant in vivo indices of T-cell-mediated immune function in healthy older persons.

N-acetylcysteine. N-acetylcysteine (NAC) is an acetylated ester of the amino acid L-cysteine. NAC raises levels of glutathione, a potent internal antioxidant (Roes EM et al 2002). For many years, NAC has been used to treat bronchitis and other lung conditions as an expectorant or mucus thinner as well as an anti-inflammatory.

Rosmarinic acid. Rosmarinic acid is a plant polyphenol found in plants of the Lamiaceae genus, which includes basil, sage, mint, rosemary, and perilla leaf (al Sereiti MR et al 1999). Oral supplementation with extracts of rosmarinic acid has been shown to suppress allergic reactions in mice and, more recently, in humans (Makino T et al 2001; Takano H et al 2004). Rosmarinic acid relieves allergy symptoms by preventing the activation of immune responder cells and by inducing apoptosis, or cellular suicide, in already activated immune responder cells (Hur YG et al 2004). Natural flavonoids like rosmarinic acid kill only excess allergy-activated immune cells while leaving the vast bulk of responder cells to fight off bacteria and other foreign invaders, thus possibly preventing the progression to allergic sinusitis.

Life Extension Foundation Recommendations

People with sinusitis often benefit from steam treatments and nasal saline wash. In addition, the following supplements are suggested to prevent infection:

1)DHEA —15 to 75 milligrams (mg) for three to six weeks, followed by blood testing to make sure optimal levels of this hormone are maintained. If symptoms of an infection are just beginning, 200 to 400 mg may be taken as soon as possible.

2)Lactoferrin —900 mg daily with meals, or 1200 mg at the first sign of infection

3)Melatonin —3 to 10 mg prior to bedtime, or up to 50 mg at the first sign of infection

4)Pure Garlic —9000 mg once or twice daily (eat other food immediately after ingesting the garlic to minimize stomach or esophageal burning.)

5)Kyolic aged garlic extract—3600 mg daily

6)Essential fatty acids ­—700 to 1400 mg of EPA and 500 to 1000 mg of DHA daily with food

7)Zinc—Suck on two 24-mg lozenges every two hours while awake, beginning at the first sign of symptoms. This should be continued for only a few days to avoid toxic side effects. Continue with 30 mg of orally ingested zinc daily.

8)Beta-carotene— 25,000 international units (IU) daily

9)Vitamin C—2.5 to 6 grams (g) daily

10)Vitamin E —400 IU of alpha-tocopherol and 200 mg or more of gamma-tocopherol daily

11)NAC— 600 mg twice daily with vitamin C
Propolis —500 to 1500 mg daily

12)Green tea —725 mg green tea powder extract. Use a decaffeinated formula if you are sensitive to caffeine.

13)Rosmarinic acid—100 mg daily


Sinusitis Safety Caveats

An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These include:

Beta-Carotene

1)Do not take beta-carotene if you smoke. Daily intake of 20 milligrams or more has been associated with a higher incidence of lung cancer in smokers.

2)Taking 30 milligrams or more daily for prolonged periods can cause carotenoderma, a yellowish skin discoloration (carotenoderma can be distinguished from jaundice because the whites of the eyes are not discolored in carotenoderma).
DHEA

3)Do not take DHEA if you could be pregnant, are breastfeeding, or could have prostate, breast, uterine, or ovarian cancer.

4)DHEA can cause androgenic effects in woman such as acne, deepening of the voice, facial hair growth and hair loss.

EPA/DHA

1)Consult your doctor before taking EPA/DHA if you take warfarin (Coumadin). Taking EPA/DHA with warfarin may increase the risk of bleeding.

2)Discontinue using EPA/DHA 2 weeks before any surgical procedure.

Garlic

1)Garlic has blood-thinning, anticlotting properties.

2)Discontinue using garlic before any surgical procedure.

3)Garlic can cause headache, muscle pain, fatigue, vertigo, watery eyes, asthma, and gastrointestinal symptoms such as nausea and diarrhea.

4)Ingesting large amounts of garlic can cause bad breath and body odor.

Green Tea

1)Consult your doctor before taking green tea extract if you take aspirin or warfarin (Coumadin). Taking green tea extract and aspirin or warfarin can increase the risk of bleeding.

2)Discontinue using green tea extract 2 weeks before any surgical procedure. Green tea extract may decrease platelet aggregation.

3)Green tea extract contains caffeine, which may produce a variety of symptoms including restlessness, nausea, headache, muscle tension, sleep disturbances, and rapid heartbeat.

Melatonin

1)Do not take melatonin if you are depressed.

2)Do not take high doses of melatonin if you are trying to conceive. High doses of melatonin have been shown to inhibit ovulation.

3)Melatonin can cause morning grogginess, a feeling of having a hangover or a “heavy head,” or gastrointestinal symptoms such as nausea and diarrhea.

NAC

1)NAC clearance is reduced in people who have chronic liver disease.

2)Do not take NAC if you have a history of kidney stones (particularly cystine stones).

3)NAC can produce a false-positive result in the nitroprusside test for ketone bodies used to detect diabetes.

4)Consult your doctor before taking NAC if you have a history of peptic ulcer disease. Mucolytic agents may disrupt the gastric mucosal barrier.

5)NAC can cause headache (especially when used along with nitrates) and gastrointestinal symptoms such as nausea and diarrhea.

Propolis

1)Propolis, when ingested, can cause hypersensitivity reactions such as rhinitis, conjunctivitis, rash, and bronchospasm.

Vitamin C

1)Do not take vitamin C if you have a history of kidney stones or of kidney insufficiency (defined as having a serum creatine level greater than 2 milligrams per deciliter and/or a creatinine clearance less than 30 milliliters per minute.

2)Consult your doctor before taking large amounts of vitamin C if you have hemochromatosis, thalassemia, sideroblastic anemia, sickle cell anemia, or erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency. You can experience iron overload if you have one of these conditions and use large amounts of vitamin C.

Vitamin E

1)Consult your doctor before taking vitamin E if you take warfarin (Coumadin).

2)Consult your doctor before taking high doses of vitamin E if you have a vitamin K deficiency or a history of liver failure.

3)Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia.

4)Discontinue using vitamin E 1 month before any surgical procedure.