Friday, July 08, 2005

Astragalus (Astragalus membranaceus)

Astragalus (Astragalus membranaceus)


Background


Astragalus products are derived from the roots of Astragalus membranaceus or related species, which are native to China. In traditional Chinese medicine, astragalus is commonly found in mixtures with other herbs, and is used in the treatment of numerous ailments, including heart, liver, and kidney diseases, as well as cancer, viral infections, and immune system disorders. Western herbalists began using astragalus in the 1800s as an ingredient in various tonics. The use of astragalus became popular in the 1980s based on theories about anti-cancer properties, although these proposed effects have not been clearly demonstrated in reliable human studies.

Some medicinal uses of astragalus are based on its proposed immune stimulatory properties, reported in preliminary laboratory and animal experiments, but not conclusively demonstrated in humans. Most astragalus research has been conducted in China, and has not been well designed or reported.

Gummy sap (tragacanth) from astragalus is used as a thickener (ice cream), emulsifier, denture adhesive, and anti-diarrheal agent.

Synonyms


Astragalus trigonus, Astragalus gummifera, Astragalus mollissimus, Astragalus lentiginosus , astragel, baak kei, beg kei, bei qi, buck qi, Fabacea (family) , goat's horn, goat's thorn, green dragon, gum dragon, gum tragacanthae, gummi tragacanthae, hoang ky, hog gum, huang-chi, Huang Qi, huangoi, huangqi, hwanggi, ji cao, Leguminosae (family), locoweed, membranous milk vetch, milk vetch, mongolian milk, mongolian milk vetch, neimeng hhuangqi, ogi, ougi, radix astragali, spino santo, Syrian tragacanth, tai shen, tragacanth, wong kei, yellow vetch, Zhongfengnaomitong.

Selected combination products that include this agent : Astragalus-Power, Baoyuan Dahuang, Biomune OSF Plus, Bu Zhong Yi Qi Tang, CH-100, Chi Power, Chinese Thermo-Chi, Deep Defense, Energy Boost Tincture, Equi-lizer Fast Start, Excel Energy, Fast Start, Fit America Natural Weight Control Aid, Formula One, Formula 3, Formula 3 Cell Activator, Fu-Zheng, Han-Dan-Gan-Le, Herbal Balance, Intra, Jian Yan Ling (JYL), Jiangtangjia, Magic Herb Diet Plus Formula + Chromium Picolinate, Man-Shen-Ling (MSL), Master Herb with Chromium Picolinate, Megawatt, Nature's Nutrition Formula One, Nature's Power Trim Super Fat Burner, New Image, New Image Plus, Sanhuang, Shengxue Mixture (SXM), Shen-Qi, Shi-quan-da-bu-tang (SQT), Thermojetics Beige, Tri-Chromaleane, Ultra Energy Now, Vita Chromaleane, Yi-qi Huo-xue injection (YHI), Yogi Herbal Tea.

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidenceGrade*Cancer
Although early laboratory and animal studies report increased immune cell function and reduced cancer cell growth associated with the use of astragalus, there is no reliable human evidence in these areas. Due to a lack of well-designed research, a firm conclusion cannot be drawn.

C
Chemotherapy side effects
In Chinese medicine, astragalus-containing herbal mixtures are sometimes used with the intention to reduce side effects of cancer treatments. Due to a lack of well-designed research, a firm conclusion cannot be drawn.
C
Low white blood cell count
Astragalus has been suggested as an immune system stimulant in preliminary laboratory and animal research, and in traditional accounts. There are published reports from China of white blood cell counts increasing during the use of astragalus preparations, although details are limited. Reliable scientific study has not been conducted in this area. High quality human research is necessary before a firm conclusion can be drawn.
C
Immune stimulation
Astragalus has been suggested as an immune system stimulant in preliminary laboratory and animal research, and in traditional accounts. Reliable human studies are lacking. High quality human research is necessary before a firm conclusion can be drawn.
C
Anti-viral activity
Anti-viral activity has been reported with the use of astragalus in laboratory and animal studies. Limited human research has examined the use of astragalus for viral infections in the lung, heart (pericarditis), liver (hepatitis B and C), cervix (papilloma virus), and in HIV disease. Studies have included combinations of astragalus with the drug interferon, or as a part of herbal mixtures. However, most studies have been small and poorly designed. Due to a lack of well-designed research, no firm conclusions can be drawn.
C
Upper respiratory tract infection
Astragalus is often used in Chinese medicine as a part of herbal mixtures to prevent or treat upper respiratory tract infections. Anti-viral activity has been reported in laboratory and animal studies, and in limited human reports. However, most studies have been small and poorly designed. Due to a lack of well-designed research, no firm conclusions can be drawn.
C
Coronary artery disease
In Chinese medicine, herbal mixtures containing astragalus have been used to treat heart diseases. There are several human case reports of reduced symptoms and improved heart function, although these are not well described. High quality human research is necessary before a conclusion can be drawn.
C
Heart failure
In Chinese medicine, herbal mixtures containing astragalus have been used to treat various heart diseases. There are several human case reports of reduced symptoms and improved heart function, and diuretic ("water pill") effects, although these are not well described. High quality human research is necessary before a conclusion can be drawn.
C
Myocarditis/endocarditis (heart infections)
Anti-viral activity has been reported in laboratory studies and animal models of myocarditis/endocarditis. Human research is limited in this area, and further research is necessary before a conclusion can be drawn.
C
Renal failure
Several animal and human studies report that kidney damage from toxins and kidney failure may be improved with the use of astragalus-containing herbal mixtures. Overall, this research has been poorly designed and reported. Astragalus alone has not been well evaluated. Better quality research is necessary before a conclusion can be drawn.
C
Liver protection
Several animal and human studies report that astragalus may protect the liver from damage related to toxins or hepatitis B and C. Overall, this research has been poorly designed and reported. Astragalus alone has not been well evaluated. Better quality research is necessary before a conclusion can be drawn.
C
ya you betcha
* Key to grades
A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use (it may not work);
F: Strong scientific evidence against this use (it likely does not work).


Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Adrenal insufficiency (Addison's disease), aging, AIDS/HIV, allergies, Alzheimer's disease, anemia, angina, ankylosing spondylitis, anorexia, antifungal, antimicrobial, antioxidant, asthma, blood thinner, bone-marrow suppression from cancer or HIV, bronchitis, cervicitis, "chi deficiency" (fatigue, weakness, loss of appetite), chronic fatigue syndrome, chronic hepatitis, cleanser, cyclosporine-induced immune suppression, dementia, demulcent, denture adhesive (astragalus sap), diabetes, diabetic foot ulcers, diabetic neuropathy, diarrhea, digestion enhancement, diuretic (urination stimulant), edema, fatigue, fever, gangrene, gastrointestinal disorders, genital herpes, graft-versus-host disease, hearing damage from toxins/gentamicin, heart attack, hemorrhage (bleeding), hemorrhoids, high cholesterol, high blood pressure, hyperthyroid, insomnia, joint pain, laxative, leprosy, leukemia, liver disease, low blood platelets, lung cancer, memory, menstrual disorders, metabolic disorders, minimal brain dysfunction, myalgia (muscle pain), myasthenia gravis, nephritis, night sweats, palpitations, pelvic congestion syndrome, postpartum fever, postpartum urinary retention, prostatitis, rectal prolapse, rotovirus enterocolitis (infants), shortness of breath, sperm motility, stamina/endurance enhancement, stomach ulcer, stroke, sweating (excessive), systemic lupus erythematosus (SLE), tissue oxygenation, uterine prolapse, uterine bleeding, weight loss, wound healing.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Standardization

Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the "active" ingredients. Anecdotal reports have recommended astragalus to be standardized to a minimum of 0.4% 4-hydroxy-3-methoxy-isoflavone-7-glycoside per dose. However, since astragalus is often added to herbal mixtures with unclear amounts used, standardization is not always possible.

Adults (18 years and older)

General use by mouth : In Chinese medicine, astragalus is used in soups, teas, extracts, and pill form. In practice and in most scientific studies, astragalus is one component of multi-herb mixtures. Therefore, precise dosing of astragalus alone is not clear. Safety and effectiveness are not clearly established for any particular dose. Various doses of astragalus have been used or studied, including 250 to 500 milligrams of extract taken 4 times daily; 1 to 30 grams of dried root taken daily (doses as high as 60 grams have been reported); or 500 to 1000 milligrams of root capsules taken 3 times daily. Dosing of tinctures or fluid extracts depends on strength of preparations.

Note : In theory, consumption of the tragacanth (gummy sap derived from astragalus) may reduce absorption of drugs taken by mouth, and should be taken at separate times.

Children (younger than 18 years)

There is not enough scientific data to recommend astragalus for use in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

In theory, patients with allergies to members of the Leguminosae (pea) family may react to astragalus. Cross-reactivity with quillaja bark (soapbark) has been reported for astragalus gum tragacanth.

Side Effects and Warnings

Some species of astragalus have caused poisoning in livestock, although these types are usually not used in human preparations (which primarily include Astragalus membranaceus ). Livestock toxicity, referred to as "locoweed" poisoning, has occurred with species that contain swainsonine ( Astragalus lentiginosus, Astragalus mollissimus, Astragalus nothrosys, Astragalus pubentissimus, Astragalus thuseri, Astragalus wootoni ), or in species that accumulate selenium ( Astragalus bisulcatus, Astragalus flavus, Astragalus praelongus, Astragalus saurinus, Astragalus tenellus ).

Overall, it is difficult to determine the side effects or toxicity of astragalus, because it is most commonly used in combination with other herbs. There are numerous reports of side effects ranging from mild to deadly in the United States Food and Drug Administration computer database, although most of these are with multi-ingredient products, and cannot be attributed to astragalus specifically. Astragalus used alone and in recommended doses is traditionally considered to be safe, although safety is not well studied. The most common side effects appear to be mild stomach upset and allergic reactions. In the United States, tragacanth (astragalus gummy sap) has been classified as GRAS (generally recognized as safe) for food use, but astragalus does not have GRAS status.

Based on preliminary animal studies and limited human research, astragalus may decrease blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare professional, and medication adjustments may be necessary.

Based on anecdotal reports and preliminary laboratory research, astragalus may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.

Preliminary reports of human use in China have noted decreased blood pressure at doses below 15 grams and increased blood pressure at doses above 30 grams. Animal research suggests possible blood pressure lowering effects. Due to a lack of well-designed studies, no firm conclusions can be drawn. Nonetheless, people with abnormal blood pressure or taking blood pressure medications should use caution and be monitored by a qualified healthcare professional. Palpitations have been noted in human reports in China.

Based on animal study, astragalus may act as a diuretic and increase urination. In theory, this may lead to dehydration or metabolic abnormalities. There is one report of pneumonia in an infant after breathing in an herbal medicine powder including Astragalus sarcocolla .

Astragalus may increase growth hormone levels.

Pregnancy and Breastfeeding

There is not enough scientific evidence to recommend the safe use of Astragalus membranaceus during pregnancy or breastfeeding. Studies of toxic astragalus species, such as Astragalus lentiginosus or Astragalus mollissimus (locoweed) have reported harmful effects during animal pregnancies, leading to abortions or abnormal heart development.

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January 01, 2004

Astragalus (Astragalus membranaceus)

Astragalus (Astragalus membranaceus)


Background


Astragalus products are derived from the roots of Astragalus membranaceus or related species, which are native to China. In traditional Chinese medicine, astragalus is commonly found in mixtures with other herbs, and is used in the treatment of numerous ailments, including heart, liver, and kidney diseases, as well as cancer, viral infections, and immune system disorders. Western herbalists began using astragalus in the 1800s as an ingredient in various tonics. The use of astragalus became popular in the 1980s based on theories about anti-cancer properties, although these proposed effects have not been clearly demonstrated in reliable human studies.

Some medicinal uses of astragalus are based on its proposed immune stimulatory properties, reported in preliminary laboratory and animal experiments, but not conclusively demonstrated in humans. Most astragalus research has been conducted in China, and has not been well designed or reported.

Gummy sap (tragacanth) from astragalus is used as a thickener (ice cream), emulsifier, denture adhesive, and anti-diarrheal agent.

Synonyms


Astragalus trigonus, Astragalus gummifera, Astragalus mollissimus, Astragalus lentiginosus , astragel, baak kei, beg kei, bei qi, buck qi, Fabacea (family) , goat's horn, goat's thorn, green dragon, gum dragon, gum tragacanthae, gummi tragacanthae, hoang ky, hog gum, huang-chi, Huang Qi, huangoi, huangqi, hwanggi, ji cao, Leguminosae (family), locoweed, membranous milk vetch, milk vetch, mongolian milk, mongolian milk vetch, neimeng hhuangqi, ogi, ougi, radix astragali, spino santo, Syrian tragacanth, tai shen, tragacanth, wong kei, yellow vetch, Zhongfengnaomitong.

Selected combination products that include this agent : Astragalus-Power, Baoyuan Dahuang, Biomune OSF Plus, Bu Zhong Yi Qi Tang, CH-100, Chi Power, Chinese Thermo-Chi, Deep Defense, Energy Boost Tincture, Equi-lizer Fast Start, Excel Energy, Fast Start, Fit America Natural Weight Control Aid, Formula One, Formula 3, Formula 3 Cell Activator, Fu-Zheng, Han-Dan-Gan-Le, Herbal Balance, Intra, Jian Yan Ling (JYL), Jiangtangjia, Magic Herb Diet Plus Formula + Chromium Picolinate, Man-Shen-Ling (MSL), Master Herb with Chromium Picolinate, Megawatt, Nature's Nutrition Formula One, Nature's Power Trim Super Fat Burner, New Image, New Image Plus, Sanhuang, Shengxue Mixture (SXM), Shen-Qi, Shi-quan-da-bu-tang (SQT), Thermojetics Beige, Tri-Chromaleane, Ultra Energy Now, Vita Chromaleane, Yi-qi Huo-xue injection (YHI), Yogi Herbal Tea.

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidenceGrade*Cancer
Although early laboratory and animal studies report increased immune cell function and reduced cancer cell growth associated with the use of astragalus, there is no reliable human evidence in these areas. Due to a lack of well-designed research, a firm conclusion cannot be drawn.

C
Chemotherapy side effects
In Chinese medicine, astragalus-containing herbal mixtures are sometimes used with the intention to reduce side effects of cancer treatments. Due to a lack of well-designed research, a firm conclusion cannot be drawn.
C
Low white blood cell count
Astragalus has been suggested as an immune system stimulant in preliminary laboratory and animal research, and in traditional accounts. There are published reports from China of white blood cell counts increasing during the use of astragalus preparations, although details are limited. Reliable scientific study has not been conducted in this area. High quality human research is necessary before a firm conclusion can be drawn.
C
Immune stimulation
Astragalus has been suggested as an immune system stimulant in preliminary laboratory and animal research, and in traditional accounts. Reliable human studies are lacking. High quality human research is necessary before a firm conclusion can be drawn.
C
Anti-viral activity
Anti-viral activity has been reported with the use of astragalus in laboratory and animal studies. Limited human research has examined the use of astragalus for viral infections in the lung, heart (pericarditis), liver (hepatitis B and C), cervix (papilloma virus), and in HIV disease. Studies have included combinations of astragalus with the drug interferon, or as a part of herbal mixtures. However, most studies have been small and poorly designed. Due to a lack of well-designed research, no firm conclusions can be drawn.
C
Upper respiratory tract infection
Astragalus is often used in Chinese medicine as a part of herbal mixtures to prevent or treat upper respiratory tract infections. Anti-viral activity has been reported in laboratory and animal studies, and in limited human reports. However, most studies have been small and poorly designed. Due to a lack of well-designed research, no firm conclusions can be drawn.
C
Coronary artery disease
In Chinese medicine, herbal mixtures containing astragalus have been used to treat heart diseases. There are several human case reports of reduced symptoms and improved heart function, although these are not well described. High quality human research is necessary before a conclusion can be drawn.
C
Heart failure
In Chinese medicine, herbal mixtures containing astragalus have been used to treat various heart diseases. There are several human case reports of reduced symptoms and improved heart function, and diuretic ("water pill") effects, although these are not well described. High quality human research is necessary before a conclusion can be drawn.
C
Myocarditis/endocarditis (heart infections)
Anti-viral activity has been reported in laboratory studies and animal models of myocarditis/endocarditis. Human research is limited in this area, and further research is necessary before a conclusion can be drawn.
C
Renal failure
Several animal and human studies report that kidney damage from toxins and kidney failure may be improved with the use of astragalus-containing herbal mixtures. Overall, this research has been poorly designed and reported. Astragalus alone has not been well evaluated. Better quality research is necessary before a conclusion can be drawn.
C
Liver protection
Several animal and human studies report that astragalus may protect the liver from damage related to toxins or hepatitis B and C. Overall, this research has been poorly designed and reported. Astragalus alone has not been well evaluated. Better quality research is necessary before a conclusion can be drawn.
C
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* Key to grades
A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use (it may not work);
F: Strong scientific evidence against this use (it likely does not work).


Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Adrenal insufficiency (Addison's disease), aging, AIDS/HIV, allergies, Alzheimer's disease, anemia, angina, ankylosing spondylitis, anorexia, antifungal, antimicrobial, antioxidant, asthma, blood thinner, bone-marrow suppression from cancer or HIV, bronchitis, cervicitis, "chi deficiency" (fatigue, weakness, loss of appetite), chronic fatigue syndrome, chronic hepatitis, cleanser, cyclosporine-induced immune suppression, dementia, demulcent, denture adhesive (astragalus sap), diabetes, diabetic foot ulcers, diabetic neuropathy, diarrhea, digestion enhancement, diuretic (urination stimulant), edema, fatigue, fever, gangrene, gastrointestinal disorders, genital herpes, graft-versus-host disease, hearing damage from toxins/gentamicin, heart attack, hemorrhage (bleeding), hemorrhoids, high cholesterol, high blood pressure, hyperthyroid, insomnia, joint pain, laxative, leprosy, leukemia, liver disease, low blood platelets, lung cancer, memory, menstrual disorders, metabolic disorders, minimal brain dysfunction, myalgia (muscle pain), myasthenia gravis, nephritis, night sweats, palpitations, pelvic congestion syndrome, postpartum fever, postpartum urinary retention, prostatitis, rectal prolapse, rotovirus enterocolitis (infants), shortness of breath, sperm motility, stamina/endurance enhancement, stomach ulcer, stroke, sweating (excessive), systemic lupus erythematosus (SLE), tissue oxygenation, uterine prolapse, uterine bleeding, weight loss, wound healing.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Standardization

Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the "active" ingredients. Anecdotal reports have recommended astragalus to be standardized to a minimum of 0.4% 4-hydroxy-3-methoxy-isoflavone-7-glycoside per dose. However, since astragalus is often added to herbal mixtures with unclear amounts used, standardization is not always possible.

Adults (18 years and older)

General use by mouth : In Chinese medicine, astragalus is used in soups, teas, extracts, and pill form. In practice and in most scientific studies, astragalus is one component of multi-herb mixtures. Therefore, precise dosing of astragalus alone is not clear. Safety and effectiveness are not clearly established for any particular dose. Various doses of astragalus have been used or studied, including 250 to 500 milligrams of extract taken 4 times daily; 1 to 30 grams of dried root taken daily (doses as high as 60 grams have been reported); or 500 to 1000 milligrams of root capsules taken 3 times daily. Dosing of tinctures or fluid extracts depends on strength of preparations.

Note : In theory, consumption of the tragacanth (gummy sap derived from astragalus) may reduce absorption of drugs taken by mouth, and should be taken at separate times.

Children (younger than 18 years)

There is not enough scientific data to recommend astragalus for use in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

In theory, patients with allergies to members of the Leguminosae (pea) family may react to astragalus. Cross-reactivity with quillaja bark (soapbark) has been reported for astragalus gum tragacanth.

Side Effects and Warnings

Some species of astragalus have caused poisoning in livestock, although these types are usually not used in human preparations (which primarily include Astragalus membranaceus ). Livestock toxicity, referred to as "locoweed" poisoning, has occurred with species that contain swainsonine ( Astragalus lentiginosus, Astragalus mollissimus, Astragalus nothrosys, Astragalus pubentissimus, Astragalus thuseri, Astragalus wootoni ), or in species that accumulate selenium ( Astragalus bisulcatus, Astragalus flavus, Astragalus praelongus, Astragalus saurinus, Astragalus tenellus ).

Overall, it is difficult to determine the side effects or toxicity of astragalus, because it is most commonly used in combination with other herbs. There are numerous reports of side effects ranging from mild to deadly in the United States Food and Drug Administration computer database, although most of these are with multi-ingredient products, and cannot be attributed to astragalus specifically. Astragalus used alone and in recommended doses is traditionally considered to be safe, although safety is not well studied. The most common side effects appear to be mild stomach upset and allergic reactions. In the United States, tragacanth (astragalus gummy sap) has been classified as GRAS (generally recognized as safe) for food use, but astragalus does not have GRAS status.

Based on preliminary animal studies and limited human research, astragalus may decrease blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare professional, and medication adjustments may be necessary.

Based on anecdotal reports and preliminary laboratory research, astragalus may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.

Preliminary reports of human use in China have noted decreased blood pressure at doses below 15 grams and increased blood pressure at doses above 30 grams. Animal research suggests possible blood pressure lowering effects. Due to a lack of well-designed studies, no firm conclusions can be drawn. Nonetheless, people with abnormal blood pressure or taking blood pressure medications should use caution and be monitored by a qualified healthcare professional. Palpitations have been noted in human reports in China.

Based on animal study, astragalus may act as a diuretic and increase urination. In theory, this may lead to dehydration or metabolic abnormalities. There is one report of pneumonia in an infant after breathing in an herbal medicine powder including Astragalus sarcocolla .

Astragalus may increase growth hormone levels.

Pregnancy and Breastfeeding

There is not enough scientific evidence to recommend the safe use of Astragalus membranaceus during pregnancy or breastfeeding. Studies of toxic astragalus species, such as Astragalus lentiginosus or Astragalus mollissimus (locoweed) have reported harmful effects during animal pregnancies, leading to abortions or abnormal heart development.

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Zhao XZ. [Effects of Astragalus membranaceus and Tripterygium hypoglancum on natural killer cell activity of peripheral blood mononuclear in systemic lupus erythematosus]. Zhongguo Zhong Xi Yi Jie He Za Zhi 1992;12(11):669-71, 645.
Zhou Y, Hirotani M, Rui H, et al. Two triglycosidic triterpene astragalosides from hairy root cultures of Astragalus membranaceus. Phytochemistry 1995;38(6):1407-1410.
Zhou Y, Huang Z, Huang T, et al. Clinical study of Shengxue Mixture in treating aplastic anemia. Chin J Integ Trad West 2001;7(3):186-189.
Zong PP, Yan TY, Gong MM. [Clinical and experimental studies of effects of Huayu decoction on scavenging free radicals]. Zhongguo Zhong Xi Yi Jie He Za Zhi 1993;13(10):591-3, 579.
Zuo L, Guo H. [Quantitative study on synergistic effect of radix astragali A6 and acyclovir against herpes simplex virus type I by polymerase chain reaction]. Zhongguo Zhong Xi Yi Jie He Za Zhi 1998;18(4):233-235.
January 01, 2004

Wednesday, July 06, 2005

Arginine (L-Arginine)

Arginine (L-Arginine)


Background


L-arginine was first isolated in 1886. In 1932, L-arginine was found to be required for the generation of urea, which is necessary for the removal of toxic ammonia from the body. In 1939, L-arginine was also shown to be required for the synthesis of creatine. Creatine degrades to creatinine at a constant rate, and is cleared from the body by the kidney.

Arginine is considered a semi-essential amino acid, because although it is normally synthesized in sufficient amounts by the body, supplementation is sometimes required (for example, due to inborn errors of urea synthesis, protein malnutrition, excess ammonia production, excessive lysine intake, burns, infection, peritoneal dialysis, rapid growth, or sepsis). Symptoms of arginine deficiency include poor wound healing, hair loss, skin rash, constipation, and fatty liver.

Arginine is a precursor of nitric oxide, which causes blood vessel relaxation (vasodilation). Preliminary evidence suggests that arginine may be useful in the treatment of medical conditions that are improved by vasodilation, such as angina, atherosclerosis, coronary artery disease, erectile dysfunction, heart failure, intermittent claudication/peripheral vascular disease, and vascular headache. Arginine also stimulates protein synthesis and has been studied for wound healing, bodybuilding, enhancement of sperm production (spermatogenesis), and prevention of wasting in people with critical illness.

Arginine hydrochloride contains high chloride content and has been used for the treatment of metabolic alkalosis. This use should be under the supervision of a qualified healthcare professional.

Most people likely do not need to take arginine supplements because the body usually makes sufficient amounts.

Synonyms


Arg, arginine, arginine hydrochloride (intravenous formulation), ibuprofen-arginate (Spedifen®), L-arginine, 2-amino-5-guanidinopentanoic acid.

Note : Arginine vasopressin is different from arginine/L-arginine, with an entirely different mechanism. NG-monomethyl-L-arginine is different from arginine/L-arginine, and functions as an inhibitor of nitric oxide synthesis.

Dietary sources of arginine : Walnuts, filberts, pecans, Brazil nuts, sesame and sunflower seeds, brown rice, raisins, coconut, gelatin, buckwheat, almonds, barley, cashews, cereals, chicken, chocolate, corn, dairy products, meats, oats, peanuts.

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidenceGrade*Growth hormone reserve test / pituitary disorder diagnosis
Intravenously administered arginine can be used to evaluate growth hormone reserve in individuals with suspected growth hormone deficiency. For example, in patients with suspected panhypopituitarism, growth/stature abnormalities, gigantism/acromegaly, or pituitary adenoma. This is an FDA labeled indication for arginine.

A
Inborn errors of urea synthesis
In patients with inborn errors of urea synthesis, high blood ammonia levels and metabolic alkalosis may occur, particularly in patients with ornithine carbamoyl transferase (OCT) deficiency or carbomoyl phosphate synthetase (CPS) deficiency. Arginine can be a helpful treatment by shifting the way the body processes nitrogen, but should be avoided in patients with hyperargininemia (high arginine levels). Other drugs may have similar benefits, such as citrulline, sodium benzoate, or sodium phenylbutyrate, although dialysis may be necessary initially. This use of arginine should be supervised by a qualified healthcare professional.
A
Adrenoleukodystrophy (ALD)
Adrenoleukodystrophy (ALD) is a rare inherited metabolic disorder characterized by the loss of fatty coverings (myelin sheaths) on nerve fibers in the brain, and progressive destruction of the adrenal gland. ALD is inherited as an x-linked genetic trait that results in dementia and adrenal failure. Injections of arginine have been proposed to help manage this disorder, although most study results are inconclusive. Further research is needed to evaluate the use of arginine in ALD.
C
Burns
A randomized, controlled clinical trial designed to evaluate immune function of patients given 15mg of arginine orally suggests that arginine may help with the recovery of immune function and protein function in partial-thickness burn patients. Further research is necessary in this area before a conclusion can be drawn.
C
Coronary artery disease / angina
There is initial evidence from several studies that arginine taken by mouth or by injection improves exercise tolerance and blood flow in arteries of the heart. Benefits have been shown in some patients with coronary artery disease and angina. A small randomized, controlled clinical trial studied the effects of a medical food bar enriched with L-arginine and a combination of other nutrients in the management of chronic stable angina. The authors found that this arginine-rich medical food, when used with traditional therapy, improves vascular function, exercise capacity and aspects of quality of life in these patients. However, further research is needed to confirm these findings and to establish doses that may be safe and effective.
C
Critical illness
Some studies suggest that arginine may provide benefits when added to nutritional supplements during critical illnesses (for example, in patients being treated in intensive care units). However, it is unclear what the specific role of arginine may be in improving recovery. A randomized, controlled clinical trial was designed to study the effects of a high-protein formula enriched with arginine, fiber, and antioxidants in early nutrition therapy of critically ill patients. The study measured infections in the hospital intensive care unit (ICU), length of hospital stay, and death rates. Patients fed the high-protein diet enriched with arginine, fiber and antioxidants developed fewer hospital infections than patients fed a standard high-protein diet. There was no difference in length of ICU hospital stay or death rate.
C
Dental pain (ibuprofen arginate)
A well-designed multicenter, randomized controlled clinical trial found that ibuprofen-arginate (Spedifen®) reduced pain faster after dental surgery compared to conventional ibuprofen alone. The study included 498 patients who were given either ibuprofen-arginate, ibuprofen, or placebo after dental surgery. The degree of the relief of pain, onset of action, and tolerability of both ibuprofen-arginate and ibuprofen were compared. It was found that ibuprofen arginate relieved pain faster and adverse events with ibuprofen arginate were similar to those seen with ibuprofen alone. Another similar trial concluded that patients treated with ibuprofen arginate rated its overall effectiveness higher than those treated with ibuprofen alone. Adverse event profiles were similar across all treatment groups. Further research is merited in this area.
C
Erectile dysfunction
Early studies propose that men with low nitrate levels in their blood or urine may find arginine supplements to be useful for managing erectile dysfunction (ED). A randomized, controlled clinical trial reported improvements in patients with mild-to-moderate ED following use of a combination of L-arginine, glutamate and yohimbine hydrochloride. Notably, yohimbine hydrochloride is an FDA-approved therapy for this condition, and the effects caused by arginine alone in this combination therapy are difficult to determine. It is not clear what doses of arginine may be safe or effective in treating this condition, and comparisons have not been made with other agents used for ED.
C
Gastrointestinal cancer surgery
Supplementation with an oral combination of arginine and omega-3 fatty acids may reduce length of hospital stay and infections after surgery in gastrointestinal cancer patients. There is conflicting evidence as to when to give the combination (either before or after surgery). Both strategies have been reported as superior to conventional treatment (no artificial nutrition) at reducing infections after surgery and reducing hospital stay. In a large, randomized, controlled clinical trial, malnourished cancer patients were given oral enteral nutrition supplemented by arginine, omega-3 fatty acids and RNA before surgery. It was found that supplementation with the combination before surgery reduced complications after surgery and hospital stay. A different randomized, controlled clinical trial in patients with gastrointestinal cancer studied the effects of an enteral diet supplemented with arginine, omega-3 fatty acids and glutamine (administered after surgery) on immune function and inflammatory response. This study reported the supplement to be well-tolerated with positive effects on immune and inflammatory response. Further research is needed to determine the possible effects of arginine alone.
C
Heart failure (CHF)
Studies of arginine in patients with chronic heart failure have shown mixed results. Some studies report improved exercise tolerance. Additional studies are needed to confirm these findings before a firm conclusion can be drawn.
C
Heart protection during coronary artery bypass grafting (CABG)
Arginine-supplemented "blood cardioplegic solution" is proposed to have protective properties for the heart. A randomized, controlled clinical trial using this solution in patients undergoing heart surgery (coronary artery bypass grafting) reports improved heart protection. Further research is needed before a firm conclusion can be drawn.
C
High blood pressure
A small study suggests that arginine taken by mouth may help to dilate the arteries and temporarily reduce blood pressure in hypertensive patients with type 2 diabetes. Larger, high-quality studies are needed before a recommendation can be made.
C
Migraine headache
Preliminary studies suggest that adding arginine to ibuprofen therapy may decrease migraine headache pain.
C
Peripheral vascular disease / claudication
Intermittent claudication is a condition characterized by leg pain and fatigue due to buildup of cholesterol plaques or clots in leg arteries. A small number of studies report that arginine therapy may improve walking distance in patients with claudication. Further research is needed before a firm conclusion can be drawn.
C
Recovery after surgery
One study suggests that arginine may provide benefits when used as a supplement after surgery. It is not clear what the specific role of arginine may be in improving immune function, or what dose is safe or effective.
C
Wound healing
Arginine has been suggested to improve the rate of wound healing in elderly individuals. A randomized, controlled clinical trial reported improved wound healing after surgery in head and neck cancer patients, following the use of an enteral diet supplemented with arginine and fiber. Arginine has also been used topically (on the skin) to attempt to improve wound healing. Further research is necessary in this area before a firm conclusion can be drawn.
C
Kidney disease
It has been suggested that arginine may be a useful supplement in people diagnosed with kidney failure. However, results from available studies do not support this claim. A small randomized, controlled clinical trial studied the ability of L-arginine to improve dilation of blood vessels in children with chronic renal failure. Results showed that blood vessel dilation (endothelial function) was not improved with oral L-arginine suggesting that dietary supplementation is not a beneficial or useful clinical approach in children with chronic renal failure.
D
Kidney protection during angiography
The contrast media or dye used during angiography to map a patient's arteries (or during some CT scans) can be toxic to the kidneys, especially to people with pre-existing kidney disease. A randomized, parallel, double-blind clinical trial studied the use of L-arginine to protect kidneys in patients with chronic renal failure undergoing angiography. The authors found no evidence that injections of L-arginine protect the kidney from damage due to contrast. Other therapies, such as N-acetylcysteine (NAC), have been found beneficial at protecting the kidneys from contrast-induced damage, particularly in patients at high-risk such as those with diabetes.
D
Cyclosporine toxicity
Animal studies report that arginine blocks the toxic effects of cyclosporine, a drug used to prevent organ transplant rejection. However, results from studies in humans have not found that arginine offers any protection from cyclosporine-induced toxicity.
D
Infertility
Although there are several studies in this area, it is not clear what effects arginine has on improving the likelihood of getting pregnant. Early evidence does not support the finding that arginine has any benefits in women who are undergoing in vitro fertilization, or in men with abnormal sperm.
D
Interstitial cystitis
Arginine has been proposed as a treatment for interstitial cystitis (inflammation of the bladder). However, most well-designed studies in humans have not found that arginine offers any improvements in treating symptoms such as urinary frequency or urgency.
D
Asthma
Although it has been suggested that arginine may be a treatment for asthma, studies in humans have actually found that arginine worsens inflammation in the lungs and contributes to asthma symptoms. Therefore, taking arginine by mouth or by inhalation is not recommended in people with asthma.
F
* Key to grades
A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use (it may not work);
F: Strong scientific evidence against this use (it likely does not work).


Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

AIDS/HIV, ammonia toxicity, anti-aging, beta-hemoglobinopathies, cancer, cardiac syndrome X, cold prevention, cystic fibrosis, dementia, diabetes, enhanced athletic performance, enhanced immune function, glaucoma, growth hormone stimulation, heart attack, hemolytic uremic syndrome (HUS), hepatic encephalopathy, immunomodulation, infection, pulmonary hypertension (high blood pressure in the lungs), high cholesterol, increased muscle mass, infantile necrotizing enterocolitis, inflammatory bowel disease, ischemic stroke, liver disease, lower esophageal sphincter relaxation, low sperm count, metabolic acidosis, obesity, osteoporosis, pain, peritonitis, preeclampsia, pre-term labor contractions, Raynaud's phenomenon, sepsis, sickle cell anemia, stomach motility disorders, stomach ulcer, stroke, supplementation to a low protein diet, thrombotic thrombocytopenic purpura (TTP).

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Standardization:

Intravenous arginine hydrochloride is available as a 10% solution (950 mOsm/L), winth 47.5mEq chloride ion per 100mL. There is no established standardization for oral arginine products.

Note : Most people likely do not need to take arginine supplements because the body usually makes sufficient amounts.

Adults (18 years and older):

Tablets/capsules: There are no standard or well-established doses of arginine, and many different doses have been used and studied. A dose that has been studied for treating coronary artery disease is two to three grams taken by mouth three times daily for three to six months. A studied dose for heart failure is 5.6 to 12.6 grams taken by mouth every day, divided into two or three equal doses, taken for six weeks. For erectile dysfunction, 1.6 grams taken by mouth three times daily for six weeks has been studied. For low sperm count, four grams daily for three months has been used. For women undergoing in vitro (test tube) fertilization, a dose of 16 grams daily by mouth has been studied, although this therapy should be discussed with the healthcare provider coordinating the in vitro program. For interstitial cystitis, 500 milligrams taken by mouth three times daily for six weeks has been used. For the long-term management of inborn disorders of the urea cycle, doses between 0.5 to 2 grams daily have been used.

Intravenous: Doses of arginine used intravenously depend on specific institutional dosing guidelines and should be given under the supervision of a healthcare provider.

Children (younger than 18 years):

Arginine supplements are not recommended in children because there is not enough scientific information available and because of potential side effects.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Anaphylaxis (severe allergic reaction) has occurred after arginine injections. People with a known allergy should avoid arginine. Signs of allergy may include rash, itching or shortness of breath.

Side Effects and Warnings

Arginine has been well tolerated by most people in studies lasting for up to six months, although there is a possibility of serious adverse effects in some individuals.

Stomach discomfort, including nausea, stomach cramps or an increased number of stools, may occur. People with asthma may experience a worsening of symptoms if arginine is inhaled, which may be related to allergy.

Other potential side effects include low blood pressure and changes in numerous chemicals and electrolytes in the blood. Examples include high potassium, high chloride, low sodium, low phosphate, high blood urea nitrogen and high creatinine levels. People with liver or kidney disease may be especially sensitive to these complications and should avoid using arginine except under medical supervision. After injections of arginine, low back pain, flushing, headache, numbness, restless legs, venous irritation and death of surrounding tissues have been reported.

In theory, arginine may increase the risk of bleeding. Patients using anticoagulants (blood thinners) or antiplatelet drugs, or with underlying bleeding disorders, should speak with a qualified healthcare provider before using arginine and should be monitored.

Arginine may increase blood sugar levels. Caution is advised in patients taking prescription drugs to control sugar levels.

Pregnancy and Breastfeeding

Arginine cannot be recommended as a supplement during pregnancy and breast-feeding because there is not enough scientific information available.

References

Bath PM, Willmot M Leonardi-Bee J, et al. Nitric oxide donors (nitrates), L-arginine, or nitric oxide synthase inhibitors for acute stroke. Cochrane Database Syst Rev 2002;(4): CD000398.
Beale RJ, Bryg DJ, Bihari DJ. Immunonutrition in the critically ill: a systematic review of clinical outcome. Crit Care Med 1999;27 (12) :2799-2805.
Bennett-Richards KJ, Kattenhorn M, Donald AE, et al. Oral L-arginine does not improve endothelial dysfunction in children with chronic renal failure. Kidney Int 2002;62(4): 1372-1378.
Black P, Max MB' Desjardins P, Norwood T, et al. A randomized, double-blind, placebo-controlled comparison of the analgesic efficacy, onset of action, and tolerability of ibuprofen arginate and ibuprofen in postoperative dental pain. Clin Ther 2002;24(7): 1072-1089.
Boger RH, Bode-Boger SM, Thiele W, et al. Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. J Am Coll Cardiol 1998;32(5):1336-1344.
Braga M, Gianotti L, Nespoli L, Radaelli G, et al. Nutritional approach in malnourished surgical patients: a prospective randomized study. Arch Surg 2002;137(2): 174-80.
Caparros T, Lopez J, Grau T. Early enteral nutrition in critically ill patients with a high-protein diet enriched with arginine, fiber, and antioxidants compared with a standard high-protein diet. The effect on nosocomial infections and outcome. JPEN J Parenter Enteral Nutr 2001;25(6):299-308; discussion 308-309.
Carrier M, Pellerin M, Perrault LP, et al. Cardioplegic arrest with L-arginine improves myocardial protection: results of a prospective randomized clinical trial. Ann Thorac Surg 2002; 73(3): 837-41; discussion 842.
Cartledge JJ, Davies AM, Eardley I. A randomized double-blind placebo-controlled crossover trial of the efficacy of L-arginine in the treatment of interstitial cystitis. BJU Int 2000;85(4):421-426.
Cen Y, Luo XS, Liu XX. Effect of L-arginine supplementation on partial-thickness burned patients. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 1999;13(4):227-231.
Chen J, Wollman Y, Chernichovsky T, et al. Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectile dysfunction: results of a double- blind, randomized, placebo-controlled study. BJU Int 1999;83(3):269-273.
Chuntrasakul C, Siltharm S, Sarasombath S, et al. Metabolic and immune effects of dietary arginine, glutamine and omega-3 fatty acids supplementation in immunocompromised patients. J Med Assoc Thai 1998;81(5):334-343.
de Luis DA, Aller R, Izaola O, et al. Postsurgery enteral nutrition in head and neck cancer patients. Eur J Clin Nutr 2002;56(11):1126-1129.
de Luis DA, Izaola O, Cuellar L, et al. Effects of c-reactive protein and interleukins blood levels in postsurgery arginine-enhanced enteral nutrition in head and neck cancer patients. Eur J Clin Nutr 2003;57(1):96-99.
Desjardins P, Black P, Papageorge M, et al. Ibuprofen arginate provides effective relief from postoperative dental pain with a more rapid onset of action than ibuprofen. Eur J Clin Pharmacol 2002;58(6):387-94.
Gianotti L, Braga M, Nespoli L, et al. A randomized controlled trial of preoperative oral supplementation with a specialized diet in patients with gasterointestinal cancer. Evid Based Nurs 2003;6(2):47.
Huynh NT, Tayek JA. Oral arginine reduces systemic blood pressure in type 2 diabetes: its potential role in nitric oxide generation. J Am Coll Nutr 2002;21(5):422-427.
Klotz T, Mathers MJ, Braun M, et al. Effectiveness of oral L-arginine in first-line treatment of erectile dysfunction in a controlled crossover study. Urol Int 1999;63(4):220-223.
Korting G, Smith S, Wheeler M, et al. A randomized double-blind trial of oral L-arginine for treatment of interstitial cystitis. J Urol 1999;161(2):558-565.
Lebret T, Herve JM, Gorny P, et al. Efficacy and safety of a novel combination of L-arginine, glutamate, and yohimbine hydrochloride: a new oral therapy for erectile dysfunction. Eur Urol 2002;41(6):608-613.
Lekakis JP, Papathanassiou S, Papioannou TG, et al. Oral L-arginine improves endothelial dysfunction in patients with essential hypertension. Int J Cardiol 2002;86(2-3):317-323.
Maxwell AJ, Zapien MP, Pearce GL, et al. Randomized trial of a medical food for the dietary management of chronic, stable angina. J Am Coll Cardiol 2002;39(1):37-45.
McGovern MM, Wasserstein MP, Aron A, et al. Biochemical effect of intravenous arginine butyrate in X-linked adrenoleukodystrophy. J Pediatr. 2003;142(6):709-713.
Mehlisch DR, Ardia A, Pallotta T. A controlled comparative study of ibuprofen arginate versus conventional ibuprofen in the treatment of postoperative dental pain. J Clin Pharmacol 2002;42(8):904-911.
Miller HI, Dascalu A, Rassin TA, et al. Effects of an acute dose of L-arginine during coronary angiography in patients with chronice renal failure: a randomized, parallel, double-blind clinical trial. Am J Nephrol 2003;23(2):91-95.
Sandrini G, Franchini S, Lanfranchi S, et al. Effectiveness of ibuprofen-arginine in the treatment of acute migraine attacks. Int J Clin Pharmacol Res 1998;18(3):145-150.
Wu GH, Zhang YW, Wu ZH. Modulation of postoperative immune and inflammatory response by immune-enhancing enteral diet in gastrointestinal cancer patients. World J Gastroenterol 2001;7(3): 357-362.
January 01, 2004

Thursday, June 23, 2005

Antineoplastons

Antineoplastons


Background


Antineoplastons are a group of naturally occurring peptide fractions which were observed by Stanislaw Burzynski, MD, PhD in the late 1970s to be absent in the urine of cancer patients. It was hypothesized that these substances may have anti-tumor properties. In the 1980s, Burzynski identified chemical structures for several of these antineoplastons, and developed a process to prepare them synthetically. Antineoplaston A10, identified as 3-phenylacetylamino-2,6-piperidinedione, was the first to be synthesized.

The use of antineoplastons in the treatment of various cancer types has been studied in the laboratory and in animals, and in limited preliminary human research. In 1991, the Cancer Therapy Evaluation Program of the National Cancer Institute (NCI) examined records of seven patients with brain tumors treated at the Burzynski Clinic in Texas. Based on their findings, the NCI sponsored a brain tumor clinical trial. However, due to difficulty recruiting patients, and a disagreement over study design, this research was canceled. The results in nine patients included prior to cancellation were reported, but were not conclusive. In 1997, Dr. Burzynski had legal troubles for permitting antineoplastons to be shipped out of Texas.

There is a lack of sufficient evidence from randomized, controlled trials in support of antineoplastons as a cancer treatment, and antineoplastons are not FDA approved therapies. Antineoplastons are not widely available in the United States, and safety and efficacy are not proven. Multiple studies of antineoplastons in various cancers have been sponsored by the Burzynski Research Institute. In recent years, antineoplastons have also been suggested to treat other conditions such as Parkinson's disease, sickle cell anemia, and thalassemia.

Synonyms


A1, A2, A3, A4, A5, A10, A10-1, AS2-1, AS2-5, AS5, Antineoplaston A, Antineoplaston H, Antineoplaston L, Antineoplaston O, Antineoplaston F, Antineoplaston Ch, Antineoplaston K, 3-N-phenylacetylaminopiperidine-2,6 dione, Phenylacetylglutamine (PAG), Phenylacetylisoglutamine (PAIG), Phenylacetic acid (PAA), 3-phenylacetylamino-2,6-piperidinedione, sodium phenylacetate.

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidenceGrade*Cancer
There is inconclusive scientific evidence regarding the effectiveness of antineoplastons in the treatment of cancer. Several preliminary human studies (case series, phase I/II trials) have examined antineoplaston types A2, A5, A10, AS2-1, and AS2-5 for a variety of cancer types. It remains unclear if antineoplastons are effective, or what doses may be safe. Until better research is available, no clear conclusion can be drawn.

C
HIV
A small preliminary study published by Dr. Burzynski and colleagues in 1992 reported increased energy and weight in patients with HIV, as well as a decreased number of opportunistic infections, and increased CD4+ counts overall. These patients were treated with antineoplaston AS2-1. However, this evidence cannot be considered conclusive. Currently, there are drug therapy regimens available for HIV with clearly demonstrated effects ("HAART" or "highly active anti-retroviral therapy), and patients with HIV are recommended to consult with a physician about treatment options.
C
Sickle cell anemia/thalassemia
A small preliminary study reported positive findings, but there is currently insufficient evidence to make a clear recommendation in this area.
C
* Key to grades
A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use (it may not work);
F: Strong scientific evidence against this use (it likely does not work).


Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Acute lymphocytic leukemia, adenocarcinoma, aging, astrocytoma, basal cell epithelioma, bladder cancer, brain/central nervous system tumors, cholesterol/triglyceride abnormalities, chronic lymphocytic leukemia, colon cancer, encephalitis, glioblastoma, hepatocellular carcinoma, leukocytosis, malignant melanoma, medulloblastoma, metastatic synovial sarcoma, Parkinson's disease, promyelocytic leukemia, prostate cancer, rectal cancer, skin cancer, thrombocytosis.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

Various doses of antineoplastons have been used in preliminary studies. Safety and effectiveness are not proven for any specific dose or use. Doses of antineoplaston A10 used by mouth in studies range from 10 to 40 grams daily or 100 to 288 milligrams per kilogram of body weight per day. Duration of use has varied. Antineoplaston AS2-1 has been studied at doses from 12 to 30 grams daily or 97 to 130 milligrams per kilogram of body weight per day. Antineoplastons have also been studied when applied to the skin, injected through the veins (intravenous) and injected into muscles (intramuscular).

Children (younger than 18 years)

There is insufficient available data to safely recommend the use of antineoplastons in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Allergic skin rash has been reported after injection of antineoplaston AS2-1. Individuals who have reacted to antineoplastons in the past should avoid this therapy.

Side Effects and Warnings

Adverse effects are reported in several preliminary studies. It is not clear how common these reactions are, or if they occur more frequently than with placebo. Since many patients taking antineoplastons have been diagnosed with serious illnesses such as advanced cancers, it is not clear if these effects may be from the illnesses themselves, or caused by antineoplastons.

Antineoplaston therapy has been associated with drowsiness, headache, fatigue, mild dizziness/vertigo, and confusion. Antineoplaston A10 is retained in the brain tissue of animals, although the importance of this in humans is not known. Weakness, nausea, vomiting, upset stomach, abdominal pain, and increased flatulence (gas) have been reported.

Various types of antineoplastons administered from weeks to years have been associated with sore throat, fever, chills, reduced blood albumin levels, liver function test abnormalities, low blood sugar levels (hypoglycemia), low potassium, and a strong body odor similar to urine.

Palpitations, high blood pressure (hypertension), and mild peripheral edema (water retention) have been noted. Chest pressure and irregular or fast heart beat have also been observed. Joint swelling, muscle/joint pain, muscle contractions in the throat, weakness, and finger rigidity have been reported in clinical trials.

Decreases in blood platelets, red blood cells, and white blood cells have been observed. Other serious reported effects include slow or abnormal breathing, metabolic/electrolyte abnormalities, cerebral edema (brain swelling), dangerously low blood pressure (hypotension), and death.

Pregnancy and Breastfeeding

The safety of antineoplastons during pregnancy or breastfeeding is not known, and therefore cannot be recommended.

References

Badria F, Mabed M, El Awadi M, et al. Immune modulatory potentials of antineoplaston A-10 in breast cancer patients. Cancer Lett 2000;157(1):57-63.
Badria F, Mabed M, Khafagy W, et al. Potential utility of antineoplaston A-10 levels in breast cancer. Cancer Lett 2000;157(1):67-70.
Buckner JC, Malkin MG, Reed E, et al. Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma. Mayo Clin Proc 1999;74(2):137-145.
Burzynski R. Isolation, purification, and synthesis of antineoplastons. Int J Exper Clin Chemother 1989;2:63-69.
Burzynski R. Treatment of bladder cancer with antineoplaston formulations. Adv Exp Clin Chemother 1988;2:37-46.
Burzynski SR, Conde AB, Peters A, et al. Retrospective study of antineoplastons A10 and AS2-1 in primary brain tumors. Clin Drug Invest 1999;18:1-10.
Burzynski SR, Kubove E, Burzynski B. Phase I clinical studies of antineoplaston A5 injections. Drugs Exp Clin Res 1987;13 Suppl 1:37-43.
Burzynski SR, Kubove E, Burzynski B. Phase II clinical trials of antineoplaston A10 and AS2-1 infusion in astrocytoma. In: Adam D, Buchner T, Rubinstein E, editors. Recent Advances in Chemotherapy. Munich: Futuramed Publishers, 1991:2506-2507.
Burzynski SR, Kubove E, Burzynski B. Treatment of hormonally refractory cancer of the prostate with antineoplaston AS2-1. Drugs Exp Clin Res 1990;16(7):361-369.
Burzynski SR, Kubove E, Szymkowski B, et al. Phase II clinical trials of novel differentiation inducer--antineoplaston AS2-1 in AIDS and asymptomatic HIV infection [abstract]. Int Conf AIDS 1992;8(3):61 (abstract no. PuB 7074).
Burzynski SR, Kubove E. Initial clinical study with antineoplaston A2 injections in cancer patients with five years' follow-up. Drugs Exp Clin Res 1987;13 Suppl 1:1-11.
Burzynski SR, Kubove E. Phase I clinical studies of antineoplaston A3 injections. Drugs Exp Clin Res 1987;13 Suppl 1:17-29.
Burzynski SR, Kubove E. Toxicology studies on antineoplaston A10 injections in cancer patients. Drugs Exp Clin Res 1986;12 Suppl 1:47-55.
Burzynski SR. Potential of antineoplastons in diseases of old age. Drugs Aging 1995;7(3):157-167.
Burzynski SR. Toxicology studies on antineoplaston AS2-5 injections in cancer patients. Drugs Exp Clin Res 1986;12 Suppl 1:17-24.
Choi BG. Synthesis of antineoplaston A10 as potential antitumor agents. Arch Pharm Res 1998;21(2):157-163.
Green S. 'Antineoplastons' An unproved cancer therapy. JAMA 1992;267 (21) :2924-2928.
Juszkiewicz M, Chodkowska A, Burzynski SR, et al. The influence of antineoplaston A5 on particular subtypes of central dopaminergic receptors. Drugs Exp Clin Res 1995;21(4):153-156.
Kumabe T. Antineoplaston treatment for advanced hepatocellular carcinoma. Oncology Rep 1998;5(6):1363-1367.
Liau MC, Szopa M, Burzynski B, et al. Quantitative assay of plasma and urinary peptides as an aid for the evaluation of cancer patients undergoing antineoplaston therapy. Drugs Exp Clin Res 1987;13 Suppl 1:61-70.
Soltysiak-Pawluczuk D, Burzynski SR. Cellular accumulation of antineoplaston AS21 in human hepatoma cells. Cancer Lett 1995;88(1):107-112.
Sugita Y, Tsuda H, Maruiwa H, et al. The effect of Antineoplaston, a new antitumor agent on malignant brain tumors. Kurume Med J 1995;42(3):133-140.
Tsuda H, Hara H, Eriguchi N, et al. Toxicological study on antineoplastons A-10 and AS2-1 in cancer patients. Kurume Med J 1995;42(4):241-249.
Tsuda H, Iemura A, Sata M, et al. Inhibitory effect of antineoplaston A10 and AS2-1 on human hepatocellular carcinoma. Kurume Med J 1996;43(2):137-147.
Tsuda H, Sata M, Kumabe T, et al. Quick response of advanced cancer to chemoradiation therapy with antineoplastons. Oncology Rep 1998;5(3):597-600.
Tsuda H, Sata M, Saitsu H, et al. Antineoplaston AS2-1 for maintenance therapy in liver cancer. Oncol Rep 1997;4:1213-1216.
Tweddle S, James N. Lessons from antineoplaston. Lancet 1997;349(9054):741.
January 01, 2004

Sunday, June 19, 2005

American Pennyroyal (Hedeoma pulegioides L.), European Pennyroyal (Mentha pulegium L.)

American Pennyroyal (Hedeoma pulegioides L.), European Pennyroyal (Mentha pulegium L.)


Background


The essential oil of pennyroyal is considered toxic. Death has been reported after consumption of half an ounce (15mL) of the oil. A characteristic noted in most cases of pennyroyal overdose is a strong minty smell on the patient's breath. The active metabolite menthofuran can be detected by gas chromatography in urine, blood, or other tissues. Overdose management includes oral decontamination by lavage, and/or administration of activated charcoal.

The similarity of the pathogenesis of pennyroyal-induced hepatic necrosis to that produced by acetaminophen, suggests a possible role for N-acetylcysteine (NAC) in the management of pennyroyal overdose. However, this application has not been confirmed by animal or human studies.

Anecdotal evidence and one case report suggest that the essential oil of pennyroyal may function as an abortifacient and emmenagogue (menstrual flow stimulant). However, it may do so at lethal or near-lethal doses, making this action unpredictable and dangerous. Future research to determine the safety and efficacy of the less toxic aerial parts of the pennyroyal plant on the menstrual cycle are needed before a recommendation can be made.

Synonyms


Aloe herbal horse spray, American pennyroyal, brotherwort, chasse-puces, churchwort, Cunila pulegioides , dictamne de Virginie, European pennyroyal, fleabane, flea mint, fretillet, Hedeoma phlebitides, herbal horsespray, herbe aux puces, herbe de Saint-Laurent, Labiatae (family) , la menthe pouliot (French), Lamiacea (family name), Lurk-in-the-Ditch , Melissa pulegioides , mentha pouillot, Miracle Coat spray-on dog shampoo, mock pennyroyal, mosquito plant, Old World pennyroyal, pennyroyal essential oil, petit baume, piliolerial, poley, pouliot royal, pudding herb, pudding grass, pulegium, pulegium oil, Pulegium vulgare, pulioll-royall, Pulegium regium, Run-by-the-Ground, squaw balm, squawmint, stinking balm, tickweed.

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidenceGrade*Abortifacient (uterus contraction stimulant/abortion inducer)
Folkloric use and several human case reports describe use of the essential oil of pennyroyal to cause abortion. However, it may do so at deadly or toxic doses, making this an unpredictable and dangerous use.

C
Menstrual flow stimulant (emmenagogue)
Folkloric use and several human case reports describe use of the essential oil of pennyroyal as an emmenagogue (menstrual flow stimulant). However, it may do so at lethal or near-lethal doses, making this action unpredictable and dangerous.
C
* Key to grades
A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use (it may not work);
F: Strong scientific evidence against this use (it likely does not work).


Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Acne, antiseptic, anti-spasm, anxiety, asthma, cancer, chest congestion, colds, colic, cough, cramps, diarrhea, digestion, diuretic (increasing urine flow), dizziness, dysentery, fever, flavoring agent, flea control, flu, fragrance (detergents, perfumes, soaps), gallbladder disorders, gas, gout, hallucinations, headache, hysteria, immortality, indigestion, insect repellant, intestinal disorders, itchy eyes, joint problems, kidney disease, leprosy, liver disease, bruises and burns, menstrual irregularities (stimulant, regulator), mouth sores, muscle pain, nosebleeds, pneumonia, potpourri, pregnancy, premenstrual syndrome, preparing the uterus for labor, purifier (water, blood), refrigerant, respiratory ailments, sedative, skin ailments (itching, burning, bruising), snake bites (venomous), stimulant, stomach pain, sunstroke, sweating, syncope, toothache, uterine fibroids, whooping cough.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Standardization

Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the "active" ingredients. American pennyroyal may contain up to 2% of volatile oil and European pennyroyal may contain up to 1% of volatile oil. Both oils are reported to contain 85% to 92% of the pennyroyal constituent pulegone.

Adults (18 years and older)

Note : No safe dose of pennyroyal has been established. The following doses have been used, but may be toxic.

Extract (1:2) : Doses of 20 to 40 milliliters per week of pennyroyal have been used but may be toxic.

Oil : Doses of 0.5 to 3 drops of pennyroyal oil have been used but may be toxic.

Tea/infusion : Based on traditional usage, 1 or 2 cups of tea per day made from 1 to 2 teaspoons of dried leaves per cup of boiling water, steeped for 10 to 15 minutes have been used but may be toxic. Pennyroyal tincture in tea water at doses of 0.25 to 0.5 teaspoonfuls (1.25 to 2.5 milliliters) up to twice daily for treating cough, congestion, and upset stomach, has been used but may be toxic.

Topical : Crushed plant material has been rubbed on the body as an insect repellant. Use of pennyroyal tincture mixed with skin cream and rubbed on the body has also been reported.

Veterinary : Pennyroyal has been used as an herbal flea collar for animals by hanging a bag of pennyroyal from a regular collar or using a pennyroyal garland. Safety and effectiveness of these preparations have not been proven.

Children (under 18 years old)

Pennyroyal is not recommended in children due to lack of scientific study and potential toxicity.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Allergic reactions to pennyroyal or to its components, including pulegone, may occur, although there are no reliable published reports.

Side Effects and Warnings

Pennyroyal herb and volatile oils have been associated with multiple reports of toxicity and adverse effects, including seizures, loss of consciousness, and death. In animals, pennyroyal (taken by mouth or placed on the skin) has been associated with liver, lung, and brain toxicity. Doses greater than 10 milliliters of pennyroyal may be associated with death. Cases of human overdose and death have been reported in infants, children, and adults.

Pennyroyal oil toxicity may cause nausea, vomiting, abdominal pain, burning in the throat, difficulty swallowing, diarrhea, excessive sweating, chills, fever, headache, ringing in the ears, dizziness, extreme thirst, muscle spasms, restlessness, tremor, excessive talkativeness, hallucinations, agitation, drowsiness, fatigue, confusion, mania, seizures, organ failure (brain, liver, lung, kidney, heart), altered (low or high) heart rate, altered (low or high) blood pressure, slow breathing, coma, loss of consciousness, and death. Typically, the first symptoms of poisoning, from either pennyroyal oil or pennyroyal leaves, occur in the stomach and bowels, and are often apparent soon after ingestion. Symptoms in pennyroyal overdose may mimic that of acetaminophen (Tylenol®) overdose, and the use of N-acetylcysteine (an antidote used for acetaminophen toxicity) treatment may prove beneficial.

Other side effects may include contact dermatitis, rash (when placed on the skin), malaise, lethargy, agitation, abnormal sensations, or change (increase or decrease) in pupil size. There are reports that pennyroyal may cause abortion. Pennyroyal has been used historically as an emmenagogue (menstrual stimulant) and may cause menstrual bleeding. There are reports that large amounts of pennyroyal may be irritating to the urinary tract. Pennyroyal may cause hypoglycemia (low blood sugar), hemolytic anemia (low red blood cell count due to destruction of cells), disseminated intravascular coagulation (widespread abnormal clotting and/or bleeding), and metabolic acidosis.

Pregnancy and Breastfeeding

Pennyroyal is not recommended during pregnancy or breastfeeding, due to the risk of uterine contractions, stimulation of menstruation, and abortion.

Many tinctures contain high levels of alcohol, and should be avoided during pregnancy.

References

Anderson IB, Nelson SD, Blanc PD. Pennyroyal metabolites in human poisoning. Ann Intern Med 1997;126(3):250-251.
Anderson IB, Mullen WH, Meeker JE et al. Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature. Ann Intern Med 1996;124(8):726-734.
Bakerink JA, Gospe SM, Jr., Dimand RJ et al. Multiple organ failure after ingestion of pennyroyal oil from herbal tea in two infants. Pediatrics 1996;98(5):944-947.
Black DR. Pregnancy unaffected by pennyroyal usage. J Am Oseopath Assoc 1985;85(5):282.
Buechel DW, Haverlah VC, Gardner ME. Pennyroyal oil ingestion: report of a case. J Am Osteopath Assoc 1983;82 (10) :793-794.
Burkhard PR, Burkhardt K, Haenggeli CA, et al. Plant-induced seizures: reappearance of an old problem. J Neurol 1999;246(8):667-670.
Carmichael PG. Pennyroyal metabolites in human poisoning. Ann Intern Med 1997;126(3):250-251.
Chen LJ, Lebetkin EH, Burka LT. Metabolism of (R)-(+)-menthofuran in Fischer-344 rats: identification of sulfonic acid metabolites. Drug Metab Dispos 2003;31(10):1208-1213.
Chen LJ, Lebetkin EH, Burka LT. Comparative disposition of (R)-(+)-pulegone in B6C3F1 mice and F344 rats. Drug Metab Dispos 2003;31(7):892-899.
Chen LJ, Lebetkin EH, Burka LT. Metabolism of (R)-(+)-pulegone in F344 rats. Drug Metab Dispos. 2001;29(12):1567-1577.
Ciganda C, Laborde A. Herbal infusions used for induced abortion. J Toxicol Clin Toxicol 2003;41(3):235-239.
Conway GA, Slocumb JC. Plants used as abortifacients and emmenagogues by Spanish New Mexicans. J Ethnopharmacol 1979;1(3):241-261.
Giorgi DF, Lobel D, Morasco R et al. N-acetylcysteine for pennyroyal oil toxicity. Vet Human Toxicol 1994;36(4):358.
Gordon WP, Huitric AC, Seth CL, et al. The metabolism of the abortifacient terpene, (R)-(+)-pulegone, to a proximate toxin, menthofuran. Drug Metab Dispos 1987;15(5):589-594.
Gordon WP, Forte AJ, McMurtry RJ, et al. Hepatotoxicity and pulmonary toxicity of pennyroyal oil and its constituent terpenes in the mouse. Toxicol Appl Pharmacol 1982;65(3):413-424.
Khojasteh-Bakht SC, Chen W, Koenigs LL, et al. Metabolism of (R)-(+)-pulegone and (R)-(+)-menthofuran by human liver cytochrome P-450s: evidence for formation of a furan epoxide. Drug Metab Dispos 1999;27(5):574-580.
Mack RB. "Boldly they rode ... into the mouth of hell". Pennyroyal oil toxicity. N C Med J 1997;58(6):456-457.
Martins HM, Martins ML, Dias MI, et al. Evaluation of microbiological quality of medicinal plants used in natural infusions. Int J Food Microbiol 2001;68(1-2):149-153.
Mazur LJ, De Ybarrondo L, Miller J, et al. Use of alternative and complementary therapies for pediatric asthma. Tex Med 2001;97(6):64-68.
Mizutani T, Nomura H, Nakanishi K, et al. Effects of drug metabolism modifiers on pulegone-induced hepatotoxicity in mice. Res Commun Chem Pathol Pharmacol 1987;58(1):75-83.
Sudekum M, Poppenga RH, Raju N, et al. Pennyroyal oil toxicosis in a dog. J Am Vet Med Assoc 1992;200(6):817-818.
Sullivan JB Jr, Rumack BH, Thomas H Jr, et al. Pennyroyal oil poisoning and hepatotoxicity. JAMA 1979;242(26):2873-2874.
January 01, 2004

American Pennyroyal (Hedeoma pulegioides L.), European Pennyroyal (Mentha pulegium L.)

American Pennyroyal (Hedeoma pulegioides L.), European Pennyroyal (Mentha pulegium L.)


Background


The essential oil of pennyroyal is considered toxic. Death has been reported after consumption of half an ounce (15mL) of the oil. A characteristic noted in most cases of pennyroyal overdose is a strong minty smell on the patient's breath. The active metabolite menthofuran can be detected by gas chromatography in urine, blood, or other tissues. Overdose management includes oral decontamination by lavage, and/or administration of activated charcoal.

The similarity of the pathogenesis of pennyroyal-induced hepatic necrosis to that produced by acetaminophen, suggests a possible role for N-acetylcysteine (NAC) in the management of pennyroyal overdose. However, this application has not been confirmed by animal or human studies.

Anecdotal evidence and one case report suggest that the essential oil of pennyroyal may function as an abortifacient and emmenagogue (menstrual flow stimulant). However, it may do so at lethal or near-lethal doses, making this action unpredictable and dangerous. Future research to determine the safety and efficacy of the less toxic aerial parts of the pennyroyal plant on the menstrual cycle are needed before a recommendation can be made.

Synonyms


Aloe herbal horse spray, American pennyroyal, brotherwort, chasse-puces, churchwort, Cunila pulegioides , dictamne de Virginie, European pennyroyal, fleabane, flea mint, fretillet, Hedeoma phlebitides, herbal horsespray, herbe aux puces, herbe de Saint-Laurent, Labiatae (family) , la menthe pouliot (French), Lamiacea (family name), Lurk-in-the-Ditch , Melissa pulegioides , mentha pouillot, Miracle Coat spray-on dog shampoo, mock pennyroyal, mosquito plant, Old World pennyroyal, pennyroyal essential oil, petit baume, piliolerial, poley, pouliot royal, pudding herb, pudding grass, pulegium, pulegium oil, Pulegium vulgare, pulioll-royall, Pulegium regium, Run-by-the-Ground, squaw balm, squawmint, stinking balm, tickweed.

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidenceGrade*Abortifacient (uterus contraction stimulant/abortion inducer)
Folkloric use and several human case reports describe use of the essential oil of pennyroyal to cause abortion. However, it may do so at deadly or toxic doses, making this an unpredictable and dangerous use.

C
Menstrual flow stimulant (emmenagogue)
Folkloric use and several human case reports describe use of the essential oil of pennyroyal as an emmenagogue (menstrual flow stimulant). However, it may do so at lethal or near-lethal doses, making this action unpredictable and dangerous.
C
* Key to grades
A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use (it may not work);
F: Strong scientific evidence against this use (it likely does not work).


Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Acne, antiseptic, anti-spasm, anxiety, asthma, cancer, chest congestion, colds, colic, cough, cramps, diarrhea, digestion, diuretic (increasing urine flow), dizziness, dysentery, fever, flavoring agent, flea control, flu, fragrance (detergents, perfumes, soaps), gallbladder disorders, gas, gout, hallucinations, headache, hysteria, immortality, indigestion, insect repellant, intestinal disorders, itchy eyes, joint problems, kidney disease, leprosy, liver disease, bruises and burns, menstrual irregularities (stimulant, regulator), mouth sores, muscle pain, nosebleeds, pneumonia, potpourri, pregnancy, premenstrual syndrome, preparing the uterus for labor, purifier (water, blood), refrigerant, respiratory ailments, sedative, skin ailments (itching, burning, bruising), snake bites (venomous), stimulant, stomach pain, sunstroke, sweating, syncope, toothache, uterine fibroids, whooping cough.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Standardization

Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the "active" ingredients. American pennyroyal may contain up to 2% of volatile oil and European pennyroyal may contain up to 1% of volatile oil. Both oils are reported to contain 85% to 92% of the pennyroyal constituent pulegone.

Adults (18 years and older)

Note : No safe dose of pennyroyal has been established. The following doses have been used, but may be toxic.

Extract (1:2) : Doses of 20 to 40 milliliters per week of pennyroyal have been used but may be toxic.

Oil : Doses of 0.5 to 3 drops of pennyroyal oil have been used but may be toxic.

Tea/infusion : Based on traditional usage, 1 or 2 cups of tea per day made from 1 to 2 teaspoons of dried leaves per cup of boiling water, steeped for 10 to 15 minutes have been used but may be toxic. Pennyroyal tincture in tea water at doses of 0.25 to 0.5 teaspoonfuls (1.25 to 2.5 milliliters) up to twice daily for treating cough, congestion, and upset stomach, has been used but may be toxic.

Topical : Crushed plant material has been rubbed on the body as an insect repellant. Use of pennyroyal tincture mixed with skin cream and rubbed on the body has also been reported.

Veterinary : Pennyroyal has been used as an herbal flea collar for animals by hanging a bag of pennyroyal from a regular collar or using a pennyroyal garland. Safety and effectiveness of these preparations have not been proven.

Children (under 18 years old)

Pennyroyal is not recommended in children due to lack of scientific study and potential toxicity.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

Allergic reactions to pennyroyal or to its components, including pulegone, may occur, although there are no reliable published reports.

Side Effects and Warnings

Pennyroyal herb and volatile oils have been associated with multiple reports of toxicity and adverse effects, including seizures, loss of consciousness, and death. In animals, pennyroyal (taken by mouth or placed on the skin) has been associated with liver, lung, and brain toxicity. Doses greater than 10 milliliters of pennyroyal may be associated with death. Cases of human overdose and death have been reported in infants, children, and adults.

Pennyroyal oil toxicity may cause nausea, vomiting, abdominal pain, burning in the throat, difficulty swallowing, diarrhea, excessive sweating, chills, fever, headache, ringing in the ears, dizziness, extreme thirst, muscle spasms, restlessness, tremor, excessive talkativeness, hallucinations, agitation, drowsiness, fatigue, confusion, mania, seizures, organ failure (brain, liver, lung, kidney, heart), altered (low or high) heart rate, altered (low or high) blood pressure, slow breathing, coma, loss of consciousness, and death. Typically, the first symptoms of poisoning, from either pennyroyal oil or pennyroyal leaves, occur in the stomach and bowels, and are often apparent soon after ingestion. Symptoms in pennyroyal overdose may mimic that of acetaminophen (Tylenol®) overdose, and the use of N-acetylcysteine (an antidote used for acetaminophen toxicity) treatment may prove beneficial.

Other side effects may include contact dermatitis, rash (when placed on the skin), malaise, lethargy, agitation, abnormal sensations, or change (increase or decrease) in pupil size. There are reports that pennyroyal may cause abortion. Pennyroyal has been used historically as an emmenagogue (menstrual stimulant) and may cause menstrual bleeding. There are reports that large amounts of pennyroyal may be irritating to the urinary tract. Pennyroyal may cause hypoglycemia (low blood sugar), hemolytic anemia (low red blood cell count due to destruction of cells), disseminated intravascular coagulation (widespread abnormal clotting and/or bleeding), and metabolic acidosis.

Pregnancy and Breastfeeding

Pennyroyal is not recommended during pregnancy or breastfeeding, due to the risk of uterine contractions, stimulation of menstruation, and abortion.

Many tinctures contain high levels of alcohol, and should be avoided during pregnancy.

References

Anderson IB, Nelson SD, Blanc PD. Pennyroyal metabolites in human poisoning. Ann Intern Med 1997;126(3):250-251.
Anderson IB, Mullen WH, Meeker JE et al. Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature. Ann Intern Med 1996;124(8):726-734.
Bakerink JA, Gospe SM, Jr., Dimand RJ et al. Multiple organ failure after ingestion of pennyroyal oil from herbal tea in two infants. Pediatrics 1996;98(5):944-947.
Black DR. Pregnancy unaffected by pennyroyal usage. J Am Oseopath Assoc 1985;85(5):282.
Buechel DW, Haverlah VC, Gardner ME. Pennyroyal oil ingestion: report of a case. J Am Osteopath Assoc 1983;82 (10) :793-794.
Burkhard PR, Burkhardt K, Haenggeli CA, et al. Plant-induced seizures: reappearance of an old problem. J Neurol 1999;246(8):667-670.
Carmichael PG. Pennyroyal metabolites in human poisoning. Ann Intern Med 1997;126(3):250-251.
Chen LJ, Lebetkin EH, Burka LT. Metabolism of (R)-(+)-menthofuran in Fischer-344 rats: identification of sulfonic acid metabolites. Drug Metab Dispos 2003;31(10):1208-1213.
Chen LJ, Lebetkin EH, Burka LT. Comparative disposition of (R)-(+)-pulegone in B6C3F1 mice and F344 rats. Drug Metab Dispos 2003;31(7):892-899.
Chen LJ, Lebetkin EH, Burka LT. Metabolism of (R)-(+)-pulegone in F344 rats. Drug Metab Dispos. 2001;29(12):1567-1577.
Ciganda C, Laborde A. Herbal infusions used for induced abortion. J Toxicol Clin Toxicol 2003;41(3):235-239.
Conway GA, Slocumb JC. Plants used as abortifacients and emmenagogues by Spanish New Mexicans. J Ethnopharmacol 1979;1(3):241-261.
Giorgi DF, Lobel D, Morasco R et al. N-acetylcysteine for pennyroyal oil toxicity. Vet Human Toxicol 1994;36(4):358.
Gordon WP, Huitric AC, Seth CL, et al. The metabolism of the abortifacient terpene, (R)-(+)-pulegone, to a proximate toxin, menthofuran. Drug Metab Dispos 1987;15(5):589-594.
Gordon WP, Forte AJ, McMurtry RJ, et al. Hepatotoxicity and pulmonary toxicity of pennyroyal oil and its constituent terpenes in the mouse. Toxicol Appl Pharmacol 1982;65(3):413-424.
Khojasteh-Bakht SC, Chen W, Koenigs LL, et al. Metabolism of (R)-(+)-pulegone and (R)-(+)-menthofuran by human liver cytochrome P-450s: evidence for formation of a furan epoxide. Drug Metab Dispos 1999;27(5):574-580.
Mack RB. "Boldly they rode ... into the mouth of hell". Pennyroyal oil toxicity. N C Med J 1997;58(6):456-457.
Martins HM, Martins ML, Dias MI, et al. Evaluation of microbiological quality of medicinal plants used in natural infusions. Int J Food Microbiol 2001;68(1-2):149-153.
Mazur LJ, De Ybarrondo L, Miller J, et al. Use of alternative and complementary therapies for pediatric asthma. Tex Med 2001;97(6):64-68.
Mizutani T, Nomura H, Nakanishi K, et al. Effects of drug metabolism modifiers on pulegone-induced hepatotoxicity in mice. Res Commun Chem Pathol Pharmacol 1987;58(1):75-83.
Sudekum M, Poppenga RH, Raju N, et al. Pennyroyal oil toxicosis in a dog. J Am Vet Med Assoc 1992;200(6):817-818.
Sullivan JB Jr, Rumack BH, Thomas H Jr, et al. Pennyroyal oil poisoning and hepatotoxicity. JAMA 1979;242(26):2873-2874.
January 01, 2004

Thursday, June 16, 2005

Aloe (Aloe vera)

Aloe (Aloe vera)


Background


Transparent gel from the pulp of the meaty leaves of Aloe vera has been used topically for thousands of years to treat wounds, skin infections, burns, and numerous other dermatologic conditions. Dried latex from the inner lining of the leaf has traditionally been used as an oral laxative.

There is strong scientific evidence in support of the laxative properties of aloe latex, based on the well-established cathartic properties of anthroquinone glycosides (found in aloe latex). However, aloe's therapeutic value compared with other approaches to constipation remains unclear.

There is promising preliminary support from in vitro, animal, and human studies that topical aloe gel has immunomodulatory properties which may improve wound healing and skin inflammation.

Synonyms


Acemannan, Aloe africana, Aloe arborescens Miller, Aloe barbadesis, Aloe capensis, Aloe ferox, aloe latex, aloe mucilage, Aloe perfoliata, Aloe perryi baker, Aloe spicata, Aloe vulgari, Barbados aloe, bitter aloe, Burn Plant, Cape Aloe, Carrisyn, hirukattali, Curaçao aloe, elephant's gall, First-Aid Plant, Ghai kunwar, Ghikumar, Hsiang-Dan, Jelly leek, kumari, lahoi, laloi, Lily of the Desert, Lu-Hui, Medicine Plant, Mediterranean aloe, Miracle Plant, mocha aloes, musabbar, natal aloes, nohwa, Plant of Immortality, Plant of Life, rokai, sabilla, Savila, Socotrine aloe, subr, True Aloe, Venezuela Aloe, Za'bila, Zanzibar Aloe.

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidence These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. Grade* Constipation (laxative) Dried latex from the inner lining of aloe leaves has been used traditionally as a laxative taken by mouth. Although few studies have been conducted to assess this effect of aloe in humans, the laxative properties of aloe components such as aloin are well supported by scientific evidence. A combination herbal remedy containing aloe was found to be an effective laxative, although it is not clear if this effect was due to aloe or to other ingredients in the product. Further study is needed to establish dosing and to compare the effectiveness and safety of aloe with other commonly used laxatives. A Seborrheic dermatitis (seborrhea, dandruff) One study using 30% aloe lotion suggests effectiveness for treating seborrheic dermatitis when applied to the skin twice daily for 4-6 weeks. Further study is needed in this area before a strong recommendation can be made. B Psoriasis vulgaris Evidence from one human trial suggests that 0.5% extract from aloe in a hydrophilic cream is an effective treatment of psoriasis vulgaris. However, there may have been problems with the way this study was conducted. Additional research is needed in this area before a strong recommendation can be made. B Genital herpes Limited evidence from human studies suggests that 0.5% extract from Aloe vera in a hydrophilic cream may be an effective treatment of genital herpes in men (better than aloe gel or placebo). Although seemingly well designed, there may have been problems with the way these studies were conducted. Additional research is needed in this area before a strong recommendation can be made. B Skin burns Preliminary evidence suggests that aloe may be effective in promoting healing of mild to moderate skin burns. However, the existing studies are small and poor in quality, and therefore no clear conclusion can be drawn. Further study is needed in this area. C Radiation dermatitis Reports in the 1930s of topical aloe's beneficial effects on skin after radiation exposure lead to widespread use in skin products. Currently, aloe gel is sometimes recommended for radiation-induced dermatitis, although scientific evidence is lacking. Results from two human studies are inconclusive. C Canker sores (aphthous stomatitis) There is weak evidence from two studies that treatment of recurrent aphthous ulcers of the mouth with aloe gel may reduce pain and increase the amount of time between the appearance of new ulcers. Further study is needed before a recommendation can be made. C Diabetes (type 2) Laboratory studies show that aloe can stimulate insulin release from the pancreas and can lower blood glucose levels in mice. Results from two poorly conducted human trials suggest that oral aloe gel may be effective in lowering blood glucose levels, although a third, smaller study found no effect. More research is needed to explore the effectiveness and safety of aloe in diabetics. C HIV infection Acemannan, a component of aloe gel, has been shown in laboratory tests to have immune-stimulating and anti-viral activities. Results from early human studies are mixed, and due to weaknesses in the way these studies were designed, firm conclusions are not possible. Without further human trials, the evidence cannot be considered convincing either in favor or against this use of aloe. C Cancer prevention There is preliminary evidence from a small case-control study that oral aloe may reduce the risk of developing lung cancer. Further study is needed in this area to clarify if it is aloe itself or other factors that may cause this benefit. C Pressure ulcers One well-designed human trial found no benefit of topical acemannan hydrogel (a component of aloe gel) in the treatment of pressure ulcers. D Infected surgical wounds In one study, application of aloe gel to surgical wounds after abdominal surgery was found to prolong wound-healing time. Further study is needed, since wound healing is a popular use of topical aloe. Aloe cannot be recommended for application to infected surgical wounds at this time. D * Key to grades : A : Strong scientific evidence for this use; B : Good scientific evidence for this use;

C : Unclear scientific evidence for this use; D : Fair scientific evidence against this use (it may not work);

F : Strong scientific evidence against this use (it likely does not work).

Uses based on tradition or theory The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. Alopecia (hair loss), antimicrobial, arthritis, asthma, bacterial skin infections, bowel disorders, chemoprotectant, chronic fatigue syndrome, chronic leg wounds, congestive heart failure, damaged blood vessels, elevated cholesterol or other lipids, frostbite, heart disease prevention, hepatitis, kidney or bladder stones, leukemia, lichen planus stomach ulcers, parasitic worm infections, scratches or superficial wounds of the eye, skin protection during radiation therapy, sunburn, systemic lupus erythematosus, tic douloureux, untreatable tumors, vaginal contraceptive, wound healing after cosmetic dermabrasion, yeast infections of the skin.

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels and discuss doses with a qualified healthcare provider before starting therapy.

Standardization

Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the "active" ingredients.

Standardized aloe products are not widely available. Although this is likely not a concern for the use of aloe gel to the skin, it may pose dangers with oral aloe (due to potential lowering of blood sugar levels). Oral aloe preparations often contain 10-30mg hydroxyanthracene derivatives per daily dose, calculated as anhydrous aloin.

Adults (18 years and older)

Topical (on the skin):

General use : Pure Aloe vera gel is often used liberally on the skin. There are no reports that using aloe on the skin causes absorption of chemicals into the body that may cause significant side effects. Skin products are available that contain aloe alone or aloe combined with other active ingredients.

Psoriasis vulgaris : Hydrophilic cream of 0.5% (by weight) of a 50% ethanol extract of aloe, combined with mineral and castor oils, three times daily for five consecutive days per week, for up to four weeks has been studied.

Genital herpes : Hydrophilic cream of 0.5% (by weight) of a 50% ethanol extract, combined with liquid paraffin and castor oil, three times daily on lesions for five consecutive days per week, for up to two weeks has been studied.

Oral (by mouth):

Constipation : The dose often recommended is the minimum amount to maintain a soft stool, typically 0.04-0.17g of dried juice (corresponds to 10-30mg hydroxyanthraquinones). As an alternative, in combination with celandin (300mg) and psyllium (50mg), 150mg of the dried juice/day of aloe has been found effective as a laxative in research.

Diabetes (type 2) : 5-15mL of aloe juice twice daily has been used but safety and efficacy of this dose has not been proven.

HIV infection : 1000mg-1600mg of acemannan orally in four equal doses. Effectiveness and safety have not been proven by studies.

Intravenous/Intramuscular:

Four cases of death have been associated with Aloe vera injections under unclear circumstances. Oral or injected use is not recommended due to lack of safety data.

Children (younger than 18 years)

Topical (skin) use of aloe gel in children is common and appears to be well tolerated.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

People with known allergy to garlic, onions, tulips, or other plants of the Liliaceae family may have allergic reactions to aloe. Individuals using aloe gel for prolonged times have developed allergic reactions including hives and eczema-like rash.

Side Effects and Warnings

The use of aloe on surgical wounds has been reported to slow healing and, in one case, to cause redness and burning after aloe juice was applied to the face after a skin-peeling procedure (dermabrasion). Application of aloe prior to sun exposure may lead to rash in sun-exposed areas.

The use of aloe or aloe latex by mouth for laxative effects can cause cramping or diarrhea. Use for over seven days may cause dependency or worsening of constipation after the aloe is stopped. Ingestion of aloe for over one year has been reported to increase the risk of colorectal cancer. Individuals with severe abdominal pain, appendicitis, ileus (temporary paralysis of the bowel), or a prolonged period without bowel movements should not take aloe.

Electrolyte imbalances in the blood, including low potassium levels, may be caused by the laxative effect of aloe. This effect may be greater in people with diabetes or kidney disease. Low potassium levels can lead to abnormal heart rhythms or muscle weakness. People with heart disease, kidney disease, or electrolyte abnormalities should not take aloe by mouth. Healthcare providers should monitor for changes in potassium and other electrolytes in individuals who take aloe by mouth for more than a few days.

Based on a small number of human studies, aloe taken by mouth may lower blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary.

Avoid aloe vera injections, which have been associated with cases of death under unclear circumstances.

Pregnancy and Breastfeeding

Although topical (skin) use of aloe is unlikely to be harmful during pregnancy or breastfeeding, oral (by mouth) use is not recommended due to theoretical stimulation of uterine contractions. It is not known whether active ingredients of aloe may be present in breast milk. The dried juice of aloe leaves should not be consumed by breastfeeding mothers.

References

Natural Standard developed the above evidence-based patient information based on a systematic review of more than 250 scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. References about effectiveness are listed below.

Bosley C, Smith J, Baratti P, et al. A phase III trial comparing an anionic phospholipid-based (APP) cream and aloe vera-based gel in the prevention and treatment of radiation dermatitis. Int J Radiat Oncol Biol Phys 2003;57 (2 Suppl) :S438.

Choi S, Kim KW, Choi JS, et al. Angiogenic activity of beta-sitosterol in the ischaemia/reperfusion-damaged brain of Mongolian gerbil. Planta Med 2002;68(4):330-335.

Chung JG, Li YC, Lee YM, et al. Aloe-emodin inhibited N-acetylation and DNA adduct of 2-aminofluorene and arylamine N-acetyltransferase gene expression in mouse leukemia L 1210 cells. Leuk Res 2003;27(9):831-840.

Ernst E, Pittler MH, Stevinson C. Complementary/alternative medicine in dermatology: evidence-assessed efficacy of two diseases and two treatments. Am J Clin Dermatol 2002;3(5):341-348.

Ferro VA, Bradbury F, Cameron P, et al. In vitro susceptibilities of Shigella flexneri and Streptococcus pyogenes to inner gel of Aloe barbadensis Miller. Antimicrob Agents Chemother 2003;47(3):1137-9.

Furukawa F, Nishikawa A, Chihara T, Shimpo K, Beppu H, Kuzuya H, Lee IS, Hirose M. Chemopreventive effects of Aloe arborescens on N-nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis in hamsters. Cancer Lett 2002;178(2):117-22.

Grover JK, Yadav S, Vats V. Medicinal plants of India with anti-diabetic potential. J Ethnopharmacol 2002;81(1):81-100.

Heggie S, Bryant GP, Tripcony L, et al. A Phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue. Cancer Nurs 2002;25(6):442-51.

Kaufman T, Kalderon N, Ullmann Y, et al. Aloe vera gel hindered wound healing of experimental second-degree burns: a quantitative controlled study. J Burn Care Rehabil 1988;9(2):156-159.

Montaner JS, Gill J, Singer J, et al. Double-blind placebo-controlled pilot trial of acemannan in advanced human immunodeficiency virus disease. J Acquir Immune Defic Syn Hum Retrovirol 1996;12:153-157.

Olsen DL, Raub W Jr., Bradley C, et al. The effect of aloe vera gel/mild soap versus mild soap alone in preventing skin reactions in patients undergoing radiation therapy. Oncol Nurs Forum 2001;28(3):543-547.

Schmidt JM, Greenspoon JS. Aloe vera dermal wound gel is associated with a delay in wound healing. Obstet Gynecol 1991;78(1):115-117.

Syed TA, Afzal M, Ashfaq AS. Management of genital herpes in men with 0.5% Aloe vera extract in a hydrophilic cream: a placebo-controlled double-blind study. J Derm Treatment 1997;8(2):99-102.

Syed TA, Ahmad SA, Holt AH, et al. Management of psoriasis with Aloe vera extract in a hydrophilic cream: a placebo-controlled, double-blind study. Trop Med Int Health 1996;1(4):505-509.

Syed TA, Cheema KM, Ahmad SA, et al. Aloe vera extract 0.5% in hydrophilic cream versus aloe vera gel for the measurement of genital herpes in males: a placebo-controlled, double-blind, comparative study. J Eur Acad Derm Veneriol 1996;7(3):294-295.

Thomas DR, Goode PS, LaMaster K, et al. Acemannan hydrogel dressing versus saline dressing for pressure ulcers: a randomized, controlled trial. Adv Wound Care 1998;11(6):273-276.

Vardy AD, Cohen AD, Tchetov T. A double-blind, placebo-controlled trial of Aloe vera ( A. barbadensis ) emulsion in the treatment of seborrheic dermatitis. J Derm Treatment 1999;10(1):7-11.

Vogler BK, Ernst E. Aloe vera: a systematic review of its clinical effectiveness. Br J Gen Pract 1999;49(447):823-828.

Williams MS, Burk M, Loprinzi CL, et al. Phase III double-blind evaluation of an Aloe vera gel as a prophylactic agent for radiation-induced skin toxicity. Int J Radiation Oncol Biol Phys 1996;36(2):345-349.

Saturday, June 11, 2005

Alfalfa (Medicago sativa L.)

Alfalfa (Medicago sativa L.)
Background
Alfalfa has a long history of dietary and medicinal use. A small number of animal and preliminary human studies report that alfalfa supplements may lower blood levels of cholesterol and glucose. However, most research has not been well designed. Therefore, there is not enough reliable evidence to form clear conclusions in these areas.
Alfalfa supplements taken by mouth appear to be generally well tolerated. However, ingestion of alfalfa tablets has been associated with reports of a lupus-like syndrome or lupus flares. These reactions may be due to the amino acid L-canavanine which appears to be present in alfalfa seeds and sprouts, but not in the leaves. There are also rare cases of pancytopenia (low blood counts), dermatitis (skin inflammation), and gastrointestinal upset.
Synonyms
Al-fac-facah, arc, buffalo herb, California clover, Chilean clover, Fabaceae , feuille de luzerne, isoflavone, jatt, kaba yonca, Leguminosae , lucerne, medicago, mielga, mu su, purple medic, phytoestrogen, purple medick, purple medicle, sai pi li ka, saranac, Spanish clover, team, weevelchek, yonja.
Evidence
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Uses based on scientific evidenceGrade*High cholesterol Reductions in blood levels of total cholesterol and low-density lipoprotein ("bad cholesterol") have been reported in animal studies and in a small number of human cases. High-density lipoprotein ("good cholesterol") has not been altered in these cases. Although this evidence is promising, better research is needed before a firm conclusion can be reached.
CAtherosclerosis (cholesterol plaques in heart arteries) Several studies in animals report reductions in cholesterol plaques of the arteries after use of alfalfa. Well-designed research in humans is necessary before a conclusion can be drawn.
CDiabetes A small number of rat studies report reductions in blood sugar levels following ingestion of alfalfa. Human data are limited, and it remains unclear if alfalfa can aid in the control of sugars in patients with diabetes or hyperglycemia.
C
* Key to gradesA: Strong scientific evidence for this use;B: Good scientific evidence for this use;C: Unclear scientific evidence for this use;D: Fair scientific evidence against this use (it may not work);F: Strong scientific evidence against this use (it likely does not work).
Uses based on tradition or theoryThe below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Allergies, appetite stimulant, asthma, bladder disorders, blood clotting disorders, boils, cough, convalescence, diuresis (increasing urination), estrogen replacement, gastrointestinal tract disorders, gum healing after dental procedures, hay fever, increasing breast milk, indigestion, inflammation, insect bites, jaundice, kidney disorders, menopausal symptoms, nutritional support, prostate disorders, rheumatoid arthritis, scurvy, skin damage from radiation, stomach ulcers, thrombocytopenic purpura, uterine stimulant, vitamin supplementation (vitamins A,C,E,K).
Dosing
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
Standardization
There are no standard or well-studied doses of alfalfa, and many different doses are used traditionally. Safety of use beyond 8 weeks has not been proven in studies.
Adults (18 years and older)
Dried herb : 5 to 10 grams of dried herb taken by mouth three times daily has been used.
Tablets : Two tablets (one gram each) of Cholestaid® (esterin processed alfalfa) taken by mouth three times daily for up to two months, then one tablet three times daily, has been recommended by the manufacturer.
Liquid extract : 5 to 10 milliliters (one to two teaspoonfuls) of a 1:1 solution in 25% alcohol taken by mouth three times daily has been used.
Seeds : For treating high cholesterol, 40 grams of heated seeds prepared three times daily and taken by mouth with food has been used.
Children (younger than 18 years)
There is not enough scientific data to recommend alfalfa supplements for use in children, and it is not recommended due to potential side effects.
Safety
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Allergies
Alfalfa should be avoided in people with allergies to members of the Fabaceae or Leguminous plant families. It remains unclear if alfalfa cross-reacts with grass, and caution is warranted in individuals with grass allergies.
Side Effects and Warnings
Alfalfa appears to be well tolerated by most individuals, although rare serious adverse effects have been reported.
Mild gastrointestinal symptoms may occur, such as stomach discomfort, diarrhea, gas, or larger/more frequent stools. Dermatitis (skin inflammation/redness) has been reported, and may be due to alfalfa allergy.
Blood sugar levels may be reduced, based on animal studies and a human case report. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a healthcare provider, and medication adjustments may be necessary.
Lupus-like effects have been associated with alfalfa use, including antinuclear antibodies in the blood, muscle pains, fatigue, abnormal immune system function, and kidney abnormalities. Therefore, people with a history of lupus (systemic lupus erythematosus), or family history of lupus should avoid alfalfa supplements.
Other rarely reported adverse effects include abnormal blood cell counts (pancytopenia) and lowered potassium levels (hypokalemia). In theory, thyroid hormone levels may be increased, gout flares may be stimulated, and estrogen-like effects may occur.
Contamination of alfalfa products with potentially dangerous bacteria (including Escherichia coli 0157:H7, Salmonella , and Listeria monocytogenes ) has been reported.
Many tinctures/liquid extracts contain high levels of alcohol, and should be avoided when driving or operating heavy machinery.
Pregnancy and Breastfeeding
Alfalfa supplements are not recommended during pregnancy and breastfeeding due to insufficient evidence and a theoretical risk of birth defects or spontaneous abortion. Amounts found in food are generally believed to be safe. Traditionally, alfalfa is believed to stimulate breast milk production, although this has not been well studied.
Tinctures/liquid extracts may contain high levels of alcohol, and should be avoided during pregnancy.
References
Alcocer-Varela J, Iglesias A, Llorente L, et al. Effects of L-canavanine on T cells may explain the induction of systemic lupus erythematosus by alfalfa. Arthritis Rheum 1985;28(1):52-57.
Anon. From the Centers for Disease Control and Prevention. Outbreaks of Escherichia coli O157:H7 infection associated with eating alfalfa sprouts-Michigan and Virginia, June-July 1997. JAMA 1997;278 (10) :809-810.
Backer HD, Mohle-Boetani JC, Werner SB, et al. High incidence of extra-intestinal infections in a Salmonella Havana outbreak associated with alfalfa sprouts. Public Health Rep 2000;115(4):339-345.
Bengtsson AA, Rylander L, Hagmar L, Nived O, Sturfelt G. Risk factors for developing systemic lupus erythematosus: a case-control study in southern Sweden.Rheumatology (Oxford). 2002 May;41(5):563-71.
Boue SM, Wiese TE, Nehls S, Burow ME, Elliott S, Carter-Wientjes CH, Shih BY, McLachlan JA, Cleveland TE. Evaluation of the estrogenic effects of legume extracts containing phytoestrogens. J Agric Food Chem. 2003 Apr 9;51(8):2193-9.
Dong Y, Iniguez AL, Ahmer BM, Triplett EW. Kinetics and strain specificity of rhizosphere and endophytic colonization by enteric bacteria on seedlings of Medicago sativa and Medicago truncatula. Appl Environ Microbiol. 2003 Mar;69(3):1783-90.
Elakovich SD, Hampton JM. Analysis of coumestrol, a phytoestrogen, in alfalfa tablets sold for human consumption. J Agric Food Chem 1984;32(1):173-175.
Farber JM, Carter AO, Varughese PV, et al. Listeriosis traced to the consumption of alfalfa tablets and soft cheese. N Engl J Med 1990;322(5):338.
Farnsworth NR. Alfalfa pills and autoimmune diseases. Am J Clin Nutr 1995;62(5):1026-1028.
Gill CJ, Keene WE, Mohle-Boetani JC, Farrar JA, Waller PL, Hahn CG, Cieslak PR. Alfalfa seed decontamination in a Salmonella outbreak. Emerg Infect Dis. 2003 Apr;9(4):474-9.
Howard MB, Hutcheson SW. Growth dynamics of Salmonella enterica strains on alfalfa sprouts and in waste seed irrigation water. Appl Environ Microbiol. 2003 Jan;69(1):548-53.
Hwang J, Hodis HN, Sevanian A. Soy and alfalfa phytoestrogen extracts become potent low-density lipoprotein antioxidants in the presence of acerola cherry extract. J Agric Food Chem 2001;49(1):308-314.
Jackson IM. Abundance of immunoreactive thyrotropin-releasing hormone-like material in the alfalfa plant. Endocrinology 1981;108(1):344-346.
Kaufman W. Alfalfa seed dermatitis. JAMA 1954;155(12):1058-1059.
Liao CH, Fett WF. Isolation of Salmonella from alfalfa seed and demonstration of impaired growth of heat-injured cells in seed homogenates. Int J Food Microbiol. 2003 May 15;82(3):245-53.
Mahon BE, Ponka A, Hall WN, et al. An international outbreak of Salmonella infections caused by alfalfa sprouts grown from contaminated seeds. J Infect Dis 1997;175(4):876-882.
Malinow MR, Bardana EJ, Jr., Goodnight SH, Jr. Pancytopenia during ingestion of alfalfa seeds. Lancet 1981;1(8220 Pt 1):615.
Malinow MR, Bardana EJ, Jr., Pirofsky B, et al. Systemic lupus erythematosus-like syndrome in monkeys fed alfalfa sprouts: role of a nonprotein amino acid. Science 1982;216(4544):415-417.
Malinow MR, McLaughlin P, Naito HK, et al. Effect of alfalfa meal on shrinkage (regression) of atherosclerotic plaques during cholesterol feeding in monkeys. Atherosclerosis 1978;30(1):27-43.
Malinow MR, McLaughlin P, Naito HK, et al. Regression of atherosclerosis during cholesterol feeding in . Am J Cardiol 1978;41:396.
Malinow MR, McLaughlin P, Stafford C. Alfalfa seeds: effects on cholesterol metabolism. Experientia 1980;36(5):562-564.
Mohle-Boetani J, Werner B, Polumbo M, et al. From the Centers for Disease Control and Prevention. Alfalfa sprouts-Arizona, California, Colorado, and New Mexico, February-April, 2001. JAMA 2002;287(5):581-582.
Molgaard J, von Schenck H, Olsson AG. Alfalfa seeds lower low density lipoprotein cholesterol and apolipoprotein B concentrations in patients with type II hyperlipoproteinemia. Atherosclerosis 1987;65(1-2):173-179.
Morimoto I, Shiozawa S, Tanaka Y, et al. L-canavanine acts on suppressor-inducer T cells to regulate antibody synthesis: lymphocytes of systemic lupus erythematosus patients are specifically unresponsive to L-canavanine. Clin Immunol Immunopathol 1990;55(1):97-108.
Ponka A, Andersson Y, Siitonen A, et al. Salmonella in alfalfa sprouts. Lancet 1995;345:462-463.
Prete PE. The mechanism of action of L-canavanine in inducing autoimmune phenomena. Arthritis Rheum 1985;28(10):1198-1200.
Roberts JL, Hayashi JA. Exacerbation of SLE associated with alfalfa ingestion. N Engl J Med 1983;308(22):1361.
Srinivasan SR, Patton D, Radhakrishnamurthy B, et al. Lipid changes in atherosclerotic aortas of Macaca fascicularis after various regression regimens. Atherosclerosis 1980;37(4):591-601.
Story JA, LePage SL, Petro MS, et al. Interactions of alfalfa plant and sprout saponins with cholesterol in vitro and in cholesterol-fed rats. Am J Clin Nutr 1984;39(6):917-929.
Swanston-Flatt SK, Day C, Bailey CJ, et al. Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetologia 1990;33(8):462-464.
Taormina PJ, Beuchat LR, Slutsker L. Infections associated with eating seed sprouts: an international concern. Emerg Infect Dis 1999;5(5):626-634.
Van Beneden CA, Keene WE, Strang RA, et al. Multinational outbreak of Salmonella enterica serotype Newport infections due to contaminated alfalfa sprouts. JAMA 1999;281(2):158-162.
Winthrop KL, Palumbo MS, Farrar JA, Mohle-Boetani JC, Abbott S, Beatty ME, Inami G, Werner SB. Alfalfa sprouts and Salmonella Kottbus infection: a multistate outbreak following inadequate seed disinfection with heat and chlorine. J Food Prot. 2003 Jan;66(1):13-7. January 01, 2004

Sunday, January 16, 2005

ANTIOXIDANTS

How do antioxidants work?

Antioxidants act as cell protectors.

Oxygen, an essential element for life, can create damaging by-products during normal cellular metabolism. Antioxidants counteract these cellular by-products, called free radicals, and bind with them before they can cause damage. If left unchecked, free radicals may cause heart damage, cancer, cataracts, and a weak immune system.

Antioxidants work by binding to the free radicals; transforming them into non-damaging compounds; or repairing cellular damage. Antioxidants come in a variety of forms and include Vitamin C, Vitamin E, the Carotenoids, and Selenium.

"Antioxidant defense systems limit [free-radical] formation and scavenge them, but antioxidant defenses are not 100 percent efficient," said Barry Halliwell, D.Sc., of the University of London and the University of California at Davis, speaking at a symposium sponsored by the International Life Sciences Institute (ILSI). Over time, "Oxidative stress can damage proteins, lipids, DNA and carbohydrates."

In an effort to beef up bodily defenses to combat free-radical activity, scientists are studying the effects of increasing individuals' antioxidant levels through the diet and dietary supplements.

Antioxidants and cancer prevention

Considerable laboratory evidence from chemical, cell culture, and animal studies indicates that antioxidants may slow or possibly prevent the development of cancer. However, information from recent clinical trials is less clear. In recent years, large-scale, randomized clinical trials reached inconsistent conclusions.

How might antioxidants prevent cancer?

Antioxidants neutralize free radicals as the natural by-product of normal cell processes. Free radicals are molecules with incomplete electron shells which make them more chemically reactive than those with complete electron shells. Exposure to various environmental factors, including tobacco smoke and radiation, can also lead to free radical formation. In humans, the most common form of free radicals is oxygen. When an oxygen molecule (O2) becomes electrically charged or "radicalized" it tries to steal electrons from other molecules, causing damage to the DNA and other molecules. Over time, such damage may become irreversible and lead to disease including cancer. Antioxidants are often described as "mopping up" free radicals, meaning they neutralize the electrical charge and prevent the free radical from taking electrons from other molecules.

Antioxidants and exercise

Although it is well known that vitamin deficiencies can create difficulties in training and recovery, the role of antioxidant supplementation in a well nourished athlete is controversial. The experimental studies are often conflicting and conclusions are difficult to reach. Nevertheless, most of the data suggest that increased intake of vitamin E is protective against exercise induced oxidative damage. It is hypothesized that vitamin E is also involved in the recovery process following exercise. Currently, the amount of vitamin E needed to produce these effects is unknown. The diet may supply enough vitamin E in most athletes, but some may require supplementation. There is no firm data to support the use of increased amounts of the other antioxidants.

Antioxidants and performance

In general, antioxidant supplements have not been shown to be useful as performance enhancers. The one exception to this is vitamin E which has been shown to be useful in athletes exercising at high altitudes. A placebo controlled study done on mountaineers demonstrated less free radical damage and decline in anaerobic threshold in those athletes supplemented with vitamin E. Although difficult to generalize, this finding suggests that supplementation with vitamin E might be beneficial in those triathletes who are adapting to higher elevations.

Antioxidants in clinical trials

Among the most widely-publicized research trials on antioxidants was a five-year study published in the Journal of the National Cancer Institute involving approximately 30,000 residents of north-central China. Participants were given either a placebo or a dietary supplement containing one of seven vitamin-mineral combinations. Persons who received a daily dose of beta carotene, vitamin E and selenium had a reduced cancer rate of 13 percent.

Although many questions remain as to the significance of these findings for other populations, the study represents the first large-scale randomized, prospective, placebo-controlled study showing the benefits of dietary supplementation with antioxidant vitamins and minerals. Much of the previous evidence was based on epidemiological studies of populations, which suggested an association between antioxidants and disease prevention but were not designed to reveal cause and effect relationships.

In another recent study reported at the American Heart Association (AHA) Scientific Session in November, women who consumed high amounts of antioxidant containing foods had a 33 percent lower risk of heart attack and a 71 percent lower risk of stroke, than women who ate few antioxidant-containing foods.

The study involved 1,795 female nurses, each of whom had a history of heart attack, chest pain due to coronary disease, or treatment for a blockage in a coronary artery. Food intake was analyzed according to subjects' estimated consumption of vitamins C and E, carotene and riboflavin.

Even after controlling for other variables that can contribute to cardiovascular risk such as age and high blood pressure, the nurses who consumed the most dietary antioxidants had the greatest disease reduction. Individual foods most closely associated with the health benefits included carrots, spinach and other greens.

"These data suggest that people at high risk because of a history of cardiovascular disease or events may benefit the most from increased consumption of fruits and vegetables," said principal investigator JoAnn Manson, M.D., of Brigham and Women's Hospital in Boston.

"These women were at especially high risk, and any intervention that impacts on that risk could potentially save a large number of lives," Manson added. Health care costs related to cardiovascular disease are expected to exceed $117.4 billion in 1993 alone, according to AHA.

Food sources of antioxidants

Antioxidants are abundant in fruits and vegetables, as well as in other foods including nuts, grains and some meats, poultry and fish. The list below describes food sources of common antioxidants.

Beta-carotene is found in many foods that are orange in color, including sweet potatoes, carrots, cantaloupe, squash, apricots, pumpkin, and mangos. Some green leafy vegetables including collard greens, spinach, and kale are also rich in beta-carotene.

Lutein, best known for its association with healthy eyes, is abundant in green, leafy vegetables such as collard greens, spinach, and kale.

Lycopene is a potent antioxidant found in tomatoes, watermelon, guava, papaya, apricots, pink grapefruit, blood oranges, and other foods. Estimates suggest 85 percent of American dietary intake of lycopene comes from tomatoes and tomato products.

Selenium is a mineral, not an antioxidant nutrient. However, it is a component of antioxidant enzymes. Plant foods like rice and wheat are the major dietary sources of selenium in most countries. The amount of selenium in soil, which varies by region, determines the amount of selenium in the foods grown in that soil. Animals that eat grains or plants grown in selenium-rich soil have higher levels of selenium in their muscle. In the United States, meats and bread are common sources of dietary selenium. Brazil nuts also contain large quantities of selenium.

Vitamin A is found in three main forms: retinol (Vitamin A1), 3,4-didehydroretinol (Vitamin A2), and 3-hydroxy-retinol (Vitamin A3). Foods rich in vitamin A include liver, sweet potatoes, carrots, milk, egg yolks and mozzarella cheese.

Vitamin C is also called ascorbic acid, and can be found in high abundance in many fruits and vegetables and is also found in cereals, beef, poultry and fish.

Vitamin E, also known as alpha-tocopherol, is found in almonds, in many oils including wheat germ, safflower, corn and soybean oils, and also found in mangos, nuts, broccoli and other foods.



Conclusion

Antioxidants protect cells from damage caused by unstable molecules known as free radicals.

Laboratory and animal research has shown antioxidants help prevent the free radical damage that is associated with cancer. However, results from recent studies in people (clinical trials) are not consistent.

Antioxidants are provided by a healthy diet that includes a variety of fruits and vegetables.



Recommendations

Follow a balanced training program that emphasizes regular exercise and eat 5 servings of fruit or vegetables per day. This will ensure that you are developing your inherent antioxidant systems and that your diet is providing the necessary components.

Weekend warriors should strongly consider a more balanced approach to exercise. Failing that, consider supplementation.

For extremely demanding races (such as an ultradistance event), or when adapting to high altitude, consider taking a vitamin E supplement (100 to 200 IU, approximately 10 times the RDA) per day for several weeks up to and following the race.

Look for upcoming FDA recommendations, but be wary of advertising and media hype.

Do not oversupplement.



References

Frei B (ed), Grei B. Natural antioxidants in human health and disease. New York, NY: Academic Press, 1994.

Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 1993;85:1483-91.

The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effects of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994;330:1029-35.

Omenn GS, Goodman G, Thomquist M, et al. The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers. Cancer Res 1994;54(7 Suppl):2038s-43s.

Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 1996;334:1145-9.

Lee IM, Cook NR, Manson JE. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: Women's Health Study. J Natl Cancer Inst 1999;91:2102-6.