Astragalus

Overview

Astragalus is an herb from traditional Chinese medicine (TCM) which is traditionally used for its immune enhancing properties, but is also recommended in TCM for "deficiency of chi" (life force) – which might include symptoms such as lack of energy and fatigue. Similar to Echinacea, astragalus exhibits immune-enhancing effects from the polysaccharides contained in the root. Modern medical practitioners have recently become involved in researching astragalus in reducing the side effects of chemotherapy, upper respiratory infections, promoting cardiovascular health, hepatoprotection, and male infertility.

Comments

Astragalus has been used as an herbal “tonic” for centuries in Traditional Chinese Medicine (TCM) and in Native American folk medicine. As a tonic, astragalus is used primarily as a “prevention” herb throughout the cold and flu season – a different usage than the more popular Echinacea, which is best used for early stage treatment as soon as you feel a cold or flu coming on. Most of what we know about astragalus, however, comes from test tube and animal experiments, which show that astragalus can help fight bacteria and viruses by enhancing various aspects of the body's normal immune response (enhanced function of specific immune system cells such as T cells, lymphocytes and neutrophils). In TCM, astragalus is often combined with other “tonic” herbs such as Ginseng, Cordyceps or Ashwagandha, to keep the immune system “humming” during periods of high stress.

The scientific evidence for the ability of astragalus to enhance the immune system and improve cardiovascular disease and cancer comes from human, animal, and in vitro studies. Some of these studies show significant beneficial results for astragalus. However, insufficient and unreliable data exists in the uses for this herb. Unless a patient has an autoimmune disease or is taking immune suppressant medications, this herb is an option for treatment and/or symptom relief in various conditions.

Scientific Support

The astragalus root is the part that contains the important saponin and polysaccharide constituents. These saponins have diuretic effects as well as anti-inflammatory and antihypertensive activity. Due to the various elements contained in the plant, (amino acids, coumarins, flavanoids, isoflavanoids, polysaccharides, and trace minerals), it is unclear which agents provide which activities.

Several chemical constituents of astragalus have been identified as potential active compounds, including saponins, flavonoids, polysaccharides and glycosides. Astragalus is often combined with other adaptogenic herbs, such as ginseng, and promoted as a guard against various internal and external stressors. Combination of astragalus with echinacea is common for protection against common infections of the mucous membranes (cold and flu).

Most of the scientific data on astragalus comes from Chinese clinical evidence, where astragalus appears to stimulate the immune system in patients with infections. At least one clinical trial in the U.S. has shown astragalus to boost T-cell levels close to normal in some cancer patients, suggesting the possibility of a synergistic effect of astragalus with chemotherapy. In animal studies, astragalus extracts have been shown effective in preventing infection of mice by influenza virus, possibly by increasing the phagocytotic activity of the white blood cells of the immune system.

In several Chinese studies (Duan et al. 2002, Zou et al. 2003) cancer patients have responded favorably to astragalus preparations (higher remission rate), probably owing to an inhibition of chemotherapy induced immune suppression (lesser decrease of white blood cell count and higher IgG and IgM levels). Numerous animal studies have indicated astragalus also possesses broad antioxidant and hepatoprotective effects, likely due to the presence of a variety of saponin and flavonoid compounds. As a general supporter of immune system function, astragalus has been studied in rodent models and in humans with a generally beneficial, if modest, effect on maintaining immune system function during chemotherapy and radiotherapy (Cha et al. 1994, Niu et al. 2001, Wu et al. 2001).

Safety/Dosage

When used as recommended, astragalus has no known side effects, but gastrointestinal distress and diarrhea are possible at high intakes. Astragalus is available as a single-ingredient supplement, but it may be even more effective in lower doses (100-200mg/day) when combined with other immune-stimulating herbs and nutrients. Approximately 500mg per day is recommended for stimulation of the immune system and to provide resistance to the effects of stress. Divided doses of 250mg per day of a standardized (for saponins and flavonoids) root extract are preferred. Use with caution in autoimmune disease due to the immunostimulating properties of astragalus. Consider discontinuing astragalus prior to surgery as astragalus may increase the risk of bleeding.

References

1.Cha RJ, Zeng DW, Chang QS. Non-surgical treatment of small cell lung cancer with chemo-radio-immunotherapy and traditional Chinese medicine. Zhonghua Nei Ke Za Zhi 1994; 462-6.

2.Chu DT, Lepe-Zuniga J, Wong WL, LaPushin R, Mavligit GM. Fractionated extract of Astragalus membranaceus, a Chinese medicinal herb, potentiates LAK cell cytotoxicity generated by a low dose of recombinant interleukin-2. J Clin Lab Immunol. 1988 Aug;26(4):183-7.

3.Chu DT, Wong WL, Mavligit GM. Immunotherapy with Chinese medicinal herbs. II. Reversal of cyclophosphamide-induced immune suppression by administration of fractionated Astragalus membranaceus in vivo. J Clin Lab Immunol. 1988 Mar;25(3):125-9.

4.Duan P, Wang ZM. Clinical study on effect of astragalus in efficacy enhancing and toxicity reducing of chemotherapy in patients of malignant tumor. Zhongguo Zhong Xi Yi Jie He Za Zhi 2002; 22: 515-7.

5.Li SQ, Yuan RX, Gao H. Clinical observation on the treatment of ischemic heart disease with astragalus membranaceus. Zhongguo Zhong Xi Yi Jie He Za Zhi 1995; 15: 77-80.

6.Liu ZG, Xiong ZM, Yu XY. Effect of astragalus injection on immune function in patients with congestive heart failure. Zhongguo Zhong Xi Yi Jie He Za Zhi 2003; 23: 351-3.

7.Luo HM, Dai RH, Li Y. Nuclear cardiology study on effective ingredients of Astragalus membranaceus in treating heart failure Zhongguo Zhong Xi Yi Jie He Za Zhi 1995; 15: 707-9.

8.Niu HR, Lai ZH, Yuan L. Observation on effect of supplementary treatments by astragalus injection in treating senile pulmonary tuberculosis patients. Zhongguo Zhong Xi Yi Jie He Za Zhi 2001; 21: 346-50.

9.Rittenhouse JR, Lui PD, Lau BH. Chinese medicinal herbs reverse macrophage suppression induced by urological tumors. J Urol. 1991 Aug;146(2):486-90.

10.Sinclair S. Chinese herbs: a clinical review of Astragalus, Ligusticum, and Schizandrae. Altern Med Rev. 1998 Oct;3(5):338-44.

11.Sun Y, Hersh EM, Talpaz M, Lee SL, Wong W, Loo TL, Mavligit GM. Immune restoration and/or augmentation of local graft versus host reaction by traditional Chinese medicinal herbs. Cancer. 1983 Jul 1;52(1):70-3.

12.Zhang JG, Gao DS, Wei GH. Clinical study on effect of Astragalus injection on left ventricular remodeling and left ventricular function in patients with acute myocardial infarction. Zhongguo Zhong Xi Yi Jie He Za Zhi 2002; 22: 346-8.

13.Zhang ZL, Wen QZ, Liu CX. Hepatoprotective effects of astragalus root. Journal of Ethnopharmacology 1990; 30: 146-49.

14.Zhao KS, Mancini C, Doria G. Enhancement of the immune response in mice by Astragalus membranaceus extracts. Immunopharmacology. 1990 Nov-Dec;20(3):225-33.

15.Zhou ZL, Yu P, Lin D. Study on effect of astragalus injection in treating congestive heart failure. Zhongguo Zhong Xi Yi Jie He Za Zhi 2001; 21: 747-9.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Cat's Claw

Overview

Although Cat’s Claw (or “una de gato”) is generally thought of as only coming from the rainforests of Peru, it is also found in the rainforests of surrounding countries such as Brasil and Bolivia. It has numerous traditional medicine uses, along with the popular uses today of immune system stimulation/modulation. It is known to possess antioxidant and anti-inflammatory activity, and has been used for numerous illnesses such as cancer, AIDS, colds/flu, yeast infections, intestinal/gastric ulcers and both osteo- and rheumatoid arthritis.

Comments

A lively debate exists for which chemotype (eg. containing pentacyclic or tetracyclic oxindole alkaloids) of cat’s claw and which species “is the best”. A recent preclinical study using in vitro methods by Sandoval et al (2002) concluded that although both species show antioxidant and anti-inflammatory effects, the presence of oxindole or pentacyclic alkaloids did not influence these activities. Sandoval et al (2002) further concluded that U.guianensis is more potent in these activities. Saventaro is the brand name of a cat’s claw extract that contains the pentacyclic oxindole alkaloids (manufactured by an Austrian company, Immodal Pharmaka).

Another debate exists as to which part of the plant is the most efficacious. Although many references have been made to the use of the root bark traditionally, today the stem bark is more popular, mostly due to its availability and higher sustainability of harvest.

Recent animal studies on a proprietary extract of cat’s claw called C-Med 100 have found that it has the ability to increase spleen cell numbers dose-dependently, but the effect was not due to increasing proliferation rate but rather their survival rate. Thus the authors noted the possible use of this extract for patients with leukopenia (Akesson et al., 2003).

Scientific Support

Rheumatoid Arthritis

An extract of the pentacyclic chemotype of U. tomentosa was studied in 40 rheumatoid arthritis patients (also taking sulfasalazine or hydroxychloroquine) for its safety and efficacy. The study design was a 52-week 2-phase study, with the first phase consisting of 24 weeks and being double-blind and placebo-controlled, and the second phase consisting of 28 weeks with all patients taking the cat’s claw treatment. In the first phase of the study the treatment group showed a statistically significant reduction in number of painful joints compared to the placebo group. In the second phase of the study, treatment resulted in a reduction in the number of painful and swollen joints, and in the Ritchie Index compared to the post-treatment values. Minor side effects were observed and the treatment was concluded to be relatively safe and of modest benefit (Mur et al., 2002).

Osteoarthritis

Cat’s claw was studied for its effect in patients with osteoarthritis of the knee, safety and for its in-vitro antioxidant and anti-inflammatory actions. In 45 patients with osteoarthritis of the knee, freeze-dried U.guianensis was given to 30 and placebo to 15, and hematological parameters were studied. No negative effects were found on the blood, liver, or experienced side effects compared to placebo. Symptoms that were significantly reduced by treatment were pain associated with activity and medical and patient assessment scores. However, no changes were found in knee pain at rest, at night, and knee circumference. In vitro studies of antioxidant (using the DPPH free radical scavenging method) and anti-inflammatory (measuring TNFalpha, and PGE2 production) activity showed both species to be equally efficacious. Due to the dosages studied, it was hypothesized that anti-inflammatory activity may result more from ability to inhibit TNFalpha rather than PGE2 (Piscoya et al, 2001).

The proprietary cat’s claw extract called C-MED 100 was studied for its ability to affect the response to 23 valent pneumococcal vaccine. C-MED 100 had been earlier found in preclinical studies to produce immune stimulating and anti-inflammatory effects. C-MED was concluded to enhance the immune response through observed lymphocyte/neutrophil ratios of peripheral blood, and the reduction of decline of antibody titer responses to the pneumococcal vaccination at 5 months. No negative side effects were found either through medical examination, clinical chemistry or blood cell analysis (Lamm et al., 2001).

Anti-cancer

In a preliminary study, a decoction of U.tomentosa bark was given to a smoker for 15 days and found to decrease the mutagenicity induced by Salmonella typhimuriium TA98 and TA100 through urine analysis. Fractions of the plant extract were tested in vitro and found to have no mutagenic effect in strains of S. typhimurium, bur rather to be able to protect against photomutagenic effects of 8-mehoxy-psoralen and UVA. These studies confirmed earlier reports of antimutagenic activity of cat’s claw, but not of its proported mutagenic effects (Rizzi et al., 1993).

Safety / Dosage

Generally dosage ranges from 20-60 mg daily for a week, and then 20 mg daily as a maintenance dose. The standardized product containing pentacyclic oxindole alkaloids (POAs) that is manufactured by Immodal Pharmaka (Saventaro) is standardized to contain a minimum of 260 µg POAs in every 20 mg dose. The C-MED-100 product (manufactured by CampaMed) is manufactured to eliminate the indole alkaloids (<0.05%) and other high molecular weight compounds such as tannins, and to contain 8% or more carboxyl alkyl esters. The recommended dose of this product is 350 mg daily (McKenna et al., 2002).

Cat’s claw is generally regarded as safe, but it is not recommended for pregnancy or lactation because it has not been fully evaluated. Initial and temporary gastrointestinal side effects are sometimes experienced, such as gas, bloating, nausea and diarrhea.

References

1.Akesson Ch, Pero RW, Ivars F. C-Med 100, a hot water extract of Uncaria tomentosa, prolongs lymphocyte survival in vivo. Phytomedicine. 2003 Jan;10(1):23-33.

2.Lamm S, Sheng Y, Pero RW. Persistent response to pneumococcal vaccine in individuals supplemented with a novel water soluble extract of Uncaria tomentosa, C-Med-100. Phytomedicine. 2001 Jul;8(4):267-74.

3.McKenna D, Jones K, Hughes K, Humphrey S. Botanical Medicines: The Desk Reference for Major Herbal Supplements, 2nd Ed. 2002 Haworth Press; Binghamton, NY

4.Mur E, Hartig F, Eibl G, Schirmer M. Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of uncaria tomentosa for the treatment of rheumatoid arthritis. J Rheumatol. 2002 Apr;29(4):678-81.

5.Piscoya J, Rodriguez Z, Bustamante SA, Okuhama NN, Miller MJ, Sandoval M. Efficacy and safety of freeze-dried cat's claw in osteoarthritis of the knee: mechanisms of action of the species Uncaria guianensis. Inflamm Res. 2001 Sep;50(9):442-8.

6.Rizzi R, Re F, Bianchi A, De Feo V, de Simone F, Bianchi L, Stivala LA. Mutagenic and antimutagenic activities of Uncaria tomentosa and its extracts. J Ethnopharmacol. 1993 Jan;38(1):63-77.

7.Sandoval M, Okuhama NN, Zhang XJ, Condezo LA, Lao J, Angeles' FM, Musah RA, Bobrowski P, Miller MJ. Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine. 2002 May;9(4):325-37.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Colostrum

Overview

Colostrum is the clear/cloudy “pre-milk” that female mammals secrete following giving birth and prior to producing milk. Colostrum for dietary supplements is usually derived from bovine sources and contains various immunoglobulins (also called antibodies) and antimicrobial factors (i.e. lactoferrin, lactoperoxidase, lysozyme) as well as growth factors such as IGF-I and IGF-II. The concentration of IGF-I in bovine colostrum is 200-2,000 mcg/liter, whereas normal milk contains less than 10 mcg/liter. In normal healthy adults, IGF-I occurs at a concentration of approximately 200 mcg/liter in serum. In terms of immunoglobulins, colostrum generally provides concentrations of IgG, IgM, and IgA that are 100-fold higher than in normal milk. The most prevalent claims for dietary supplements containing colostrum are in the area of generalized immune function as well as the specific areas of diarrhea prevention/treatment, overall gastrointestinal support, and improved recovery from intense exercise.

Comments

The amino acid sequences of human and bovine IGF-I are identical. The increase in serum IGF-I observed in several human studies is most likely due to an enhanced stimulation of endogenous IGF-I synthesis rather than a direct absorption of the growth factor from the adult gastrointestinal tract. It is likely that the natural target of colostrum-derived growth factors is the gastrointestinal tract, whereby the increased growth and turnover of the intestine provides for a healthier gut and an increased uptake of dietary components that may enhance growth, immune competence, and athletic performance generally.

Scientific Support

Bovine colostrum contains the same disease resistance factors (immunoglobins) which are found in human breast milk and unpasteurized cow's milk. The wide variety of “immune factors” which may be effective against various viruses, bacteria, yeast and other invaders. Among these immune factors are immunoglobins (IgA, IgG, IgM), lactoferrin, lactalbumin, glycoproteins, cytokines (such as IL-1, IL-6, and interferon Y) and various polypeptides, growth factors, vitamins and minerals. The antibodies present in colostrum are thought to combine with disease-causing microorganisms in the GI tract. By adhering to pathogens, colostrum antibodies may be able to reduce the adhesive properties of bacteria and decrease their ability to attach to the intestinal wall (which could prevent their entrance into the body). It is unlikely that the “full” antimicrobial benefits of colostrum can be realized unless you happen to be a baby cow – because the immunoglobulins are largely digested in the adult gut and cannot be absorbed intact (Mero et al. 2002). It may be possible, however, for partially digested immunoglobulin fragments to retain a small portion of their functional properties and deliver these immune benefits upon absorption.

Numerous studies have been conducted in adults and children to show the benefits of ingesting colostrum in neutralizing the activity of several strains of bacteria and parasites that cause diarrhea (Ashraf et al. 2001, Bolke et al. 2002, Huppertz et al. 1999, Mitra et al. 1995, Nord et al. 1990, Okhuysen et al. 1998, Plettenberg et al. 1993, Rump et al. 1992, Sarker et al. 2001, Tacket et al. 1988, Tawfeek et al. 2003). Both the prophylactic and treatment effects of colostrum feeding against bacterial and parasitic infections of the gastrointestinal tract may be the result of direct antimicrobial effects of colostrum-derived immune factors and/or a generalized stabilization of gut barrier function (Bolke et al. 2002, Playford et al. 2001). In studies of chronic gastritis, symptoms were improved and inflammation was reduced, but there was no evidence that colostrum was directly effective against H. pylori (the bacteria that causes stomach ulcers).

In terms of sports performance, several studies have investigated athletes while consuming colostrum (up to 60 grams per day) compared to placebo or to whey protein. These studies have found variable effects on IGF-I levels, but general benefits in terms of overall athletic performance and exercise recovery (Antonio et al. 2001, Brinkworth et al. 2002, Buckley et al. 2002, Buckley et al. 2003, Coombes et al. 2002, Hoffman et al. 2002) found no differences in plasma IGF-1 concentrations in either group during the study period, but the colostrum group ran further and did more work than the placebo group (equal to a 2% increase in performance). Another study examined rowing performance in a group of elite female rowers. Eight rowers completed a 9 week training program while consuming either colostrum (60 grams per day) or whey protein. By week 9, rowers consuming colostrum had greater increases in the distance covered and work done compared to the whey protein group.

Additional studies on bovine colostrum consumption suggests that it can also deliver some generalized anti-inflammatory benefits (Bolke et al. 2002, Playford et al. 2001) and help prevent and treat the gastric injury associated with non-steroidal anti-inflammatory drugs (NSAIDs). Such effects may also be of value for the treatment of other ulcerative conditions of the bowel such as colitis and irritable bowel syndrome (Khan et al. 2002).

Taken together, the available evidence for bovine colostrum is supportive of its benefits as an effective immune-supporting supplement – particularly when interactions with pathogens in the intestinal tract are possible. It is unlikely, however, that colostrum would provide immune benefits against airborne pathogens and upper respiratory tract infections such as cold and influenza or against pollen-related allergic responses (Leiferman et al. 1975).

Safety / Dosage

No adverse side effects are expected up to doses of 60 grams per day – but those individuals with milk allergies should avoid bovine colostrum. Doses of 10 grams and up have been used in the majority of human studies and it is unknown if lower doses will provide any meaningful immune or gastrointestinal benefits. Many capsule-form products provide no more than 1 gram of colostrum per serving, while powder forms may deliver levels associated with clinical effectiveness (10 grams and higher).

References

1.Antonio J, Sanders MS, Van Gammeren D. The effects of bovine colostrum supplementation on body composition and exercise performance in active men and women. Nutrition. 2001 Mar;17(3):243-7.

2.Ashraf H, Mahalanabis D, Mitra AK, Tzipori S, Fuchs GJ. Hyperimmune bovine colostrum in the treatment of shigellosis in children: a double-blind, randomized, controlled trial. Acta Paediatr. 2001 Dec;90(12):1373-8.

3.Bolke E, Jehle PM, Hausmann F, Daubler A, Wiedeck H, Steinbach G, Storck M, Orth K. Preoperative oral application of immunoglobulin-enriched colostrum milk and mediator response during abdominal surgery. Shock. 2002 Jan;17(1):9-12.

4.Brinkworth GD, Buckley JD, Bourdon PC, Gulbin JP, David A. Oral bovine colostrum supplementation enhances buffer capacity but not rowing performance in elite female rowers. Int J Sport Nutr Exerc Metab. 2002 Sep;12(3):349-65.

5.Buckley JD, Abbott MJ, Brinkworth GD, Whyte PB. Bovine colostrum supplementation during endurance running training improves recovery, but not performance. J Sci Med Sport. 2002 Jun;5(2):65-79.

6.Buckley JD, Brinkworth GD, Abbott MJ. Effect of bovine colostrum on anaerobic exercise performance and plasma insulin-like growth factor I. J Sports Sci. 2003 Jul;21(7):577-88.

7.Casswall TH, Sarker SA, Albert MJ, Fuchs GJ, Bergstrom M, Bjorck L, Hammarstrom L. Treatment of Helicobacter pylori infection in infants in rural Bangladesh with oral immunoglobulins from hyperimmune bovine colostrum. Aliment Pharmacol Ther. 1998 Jun;12(6):563-8.

8.Coombes JS, Conacher M, Austen SK, Marshall PA. Dose effects of oral bovine colostrum on physical work capacity in cyclists. Med Sci Sports Exerc. 2002 Jul;34(7):1184-8.

9.Davidson GP, Whyte PB, Daniels E, Franklin K, Nunan H, McCloud PI, Moore AG, Moore DJ. Passive immunisation of children with bovine colostrum containing antibodies to human rotavirus. Lancet. 1989 Sep 23;2(8665):709-12.

10.Ebina T, Sato A, Umezu K, Ishida N, Ohyama S, Oizumi A, Aikawa K, Katagiri S, Katsushima N, Imai A, et al. Prevention of rotavirus infection by oral administration of cow colostrum containing antihumanrotavirus antibody. Med Microbiol Immunol (Berl). 1985;174(4):177-85.

11.Greenberg and Cello. 1996. Treatment of severe diarrhea caused by Cryptosporidium parvum with oral bovine immunoglobulins concentrate in patients with AIDS. J. AIDS and Hum. Retrovirol. 13:348-354.

12.He F, Tuomola E, Arvilommi H, Salminen S. Modulation of human humoral immune response through orally administered bovine colostrum. FEMS Immunol Med Microbiol. 2001 Aug;31(2):93-6.

13.Hofman Z, Smeets R, Verlaan G, Lugt R, Verstappen PA. The effect of bovine colostrum supplementation on exercise performance in elite field hockey players. Int J Sport Nutr Exerc Metab. 2002 Dec;12(4):461-9.

14.Huppertz HI, Rutkowski S, Busch DH, Eisebit R, Lissner R, Karch H. Bovine colostrum ameliorates diarrhea in infection with diarrheagenic Escherichia coli, shiga toxin-producing E. Coli, and E. coli expressing intimin and hemolysin. J Pediatr Gastroenterol Nutr. 1999 Oct;29(4):452-6.

15.Khan Z, Macdonald C, Wicks AC, Holt MP, Floyd D, Ghosh S, Wright NA, Playford RJ. Use of the “nutriceutical”, bovine colostrum, for the treatment of distal colitis: results from an initial study. Aliment Pharmacol Ther. 2002 Nov;16(11):1917-22.

16.Leiferman KM, Yunginger JW, Larson JB, Gleich GJ. The effect of immune milk as a treatment for ragweed pollinosis. Ann Allergy. 1975 Dec;35(6):367-71.

17.McClead RE Jr, Butler T, Rabbani GH. Orally administered bovine colostral anti-cholera toxin antibodies: results of two clinical trials. Am J Med. 1988 Dec;85(6):811-6.

18.Mero A, Kahkonen J, Nykanen T, Parviainen T, Jokinen I, Takala T, Nikula T, Rasi S, Leppaluoto J. IGF-I, IgA, and IgG responses to bovine colostrum supplementation during training. J Appl Physiol. 2002 Aug;93(2):732-9.

19.Mero A, Miikkulainen H, Riski J, Pakkanen R, Aalto J, Takala T. Effects of bovine colostrum supplementation on serum IGF-I, IgG, hormone, and saliva IgA during training. J Appl Physiol. 1997 Oct;83(4):1144-51.

20.Mitra AK, Mahalanabis D, Ashraf H, Unicomb L, Eeckels R, Tzipori S. Hyperimmune cow colostrum reduces diarrhoea due to rotavirus: a double-blind, controlled clinical trial. Acta Paediatr. 1995 Sep;84(9):996-1001.

21.Nord J, Ma P, DiJohn D, Tzipori S, Tacket CO. Treatment with bovine hyperimmune colostrum of cryptosporidial diarrhea in AIDS patients. AIDS. 1990 Jun;4(6):581-4.

22.Okhuysen PC, Chappell CL, Crabb J, Valdez LM, Douglass ET, DuPont HL. Prophylactic effect of bovine anti-Cryptosporidium hyperimmune colostrum immunoglobulin in healthy volunteers challenged with Cryptosporidium parvum. Clin Infect Dis. 1998 Jun;26(6):1324-9.

23.Playford RJ, Floyd DN, Macdonald CE, Calnan DP , Adenekan RO, Johnson W, Goodlad RA, Marchbank T. Bovine colostrum is a health food supplement which prevents NSAID induced gut damage. Gut 1999 May: 44(5):653-8.

24.Playford RJ, MacDonald CE, Calnan DP, Floyd DN, Podas T, Johnson W, Wicks AC, Bashir O, Marchbank T. Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability. Clin Sci (Lond). 2001 Jun;100(6):627-33.

25.Plettenberg A, Stoehr A, Stellbrink HJ, Albrecht H, Meigel W. A preparation from bovine colostrum in the treatment of HIV-positive patients with chronic diarrhea. Clin Investig. 1993 Jan;71(1):42-5.

26.Rump JA, Arndt R, Arnold A, Bendick C, Dichtelmuller H, Franke M, Helm EB, Jager H, Kampmann B, Kolb P, et al. Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum. Clin Investig. 1992 Jul;70(7):588-94.

27.Sarker SA, Casswall TH, Juneja LR, Hoq E, Hossain I, Fuchs GJ, Hammarstrom L. Randomized, placebo-controlled, clinical trial of hyperimmunized chicken egg yolk immunoglobulin in children with rotavirus diarrhea. J Pediatr Gastroenterol Nutr. 2001 Jan;32(1):19-25.

28.Sarker SA, Casswall TH, Mahalanabis D, Alam NH, Albert MJ, Brussow H, Fuchs GJ, Hammerstrom L. Successful treatment of rotavirus diarrhea in children with immunoglobulin from immunized bovine colostrum. Pediatr Infect Dis J. 1998 Dec;17(12):1149-54.

29.Tacket CO, Losonsky G, Link H, Hoang Y, Guesry P, Hilpert H, Levine MM. Protection by milk immunoglobulin concentrate against oral challenge with enterotoxigenic Escherichia coli. N Engl J Med. 1988 May 12;318(19):1240-3.

30.Tacket, Binion, Bostwick, Losonsky, Roy and Edelman. 1992. Efficacy of bovine milk immunoglobulins concentrate in preventing illness after Shigella flexneri challenge. Amer. J. Trop. Med. Hyg. 47:276-283.

31.Takahashi, Eisenhuth, Lee, Schachtele, Laible and Binion. 1992. Nonspecific antibacterial factors in milk from cows immunized with human oral bacterial pathogens. J. Dairy Sci. 75:1810-1820.

32.Tawfeek HI, Najim NH, Al-Mashikhi S. Efficacy of an infant formula containing anti-Escherichia coli colostral antibodies from hyperimmunized cows in preventing diarrhea in infants and children: a field trial. Int J Infect Dis. 2003 Jun;7(2):120-8.

33.Warny M, Fatimi A, Bostwick EF, Laine DC, Lebel F, LaMont JT, Pothoulakis C, Kelly CP. Bovine immunoglobulin concentrate-clostridium difficile retains C difficile toxin neutralising activity after passage through the human stomach and small intestine. Gut. 1999 Feb;44(2):212-7.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

Echinacea

Overview

Echinacea is native to the United States and a small region of southern Canada. There are nine species of Echinacea: E. angustifolia, E. dicksoni, E. dubia, E. gloruisa, E. pallida, E. paradoxa, E. purpurea, E. simulate, E. angustifoliae; however, only three of the species are normally harvested for medicinal purposes: E. angustifolia, E. pallida, and E. purpurea. Originally, Echinacea was used in North America by Native Americans for therapeutic uses such as blood purification, snake bites, infections, and malignancy. In the late 1800’s a Nebraska physician, HCF Meyer, learned of its being used by Native Americans and proposed its uses to a pharmaceutical manufacturer, Lloyd Brothers of Cincinnati. The physician expounded on the uses of Echinacea proposing that it could be used for rheumatism, streptococcal erysipelas, stomach upset, migraines, pain, sores, wounds, eczema, sore eyes, snake bites, gangrene, typhoid, diphtheria, rabies, hemorrhoids, dizziness, herbal poisoning, tumors, syphilis, malaria, and bee stings. At this point it began to be marketed as an anti-infective (Cupp, 2000; Blumenthal et al., 2000; Rotblatt and Ziment, 2002).

Today, Echinacea is mostly used as an immune modulator to aide the body in fighting or preventing infections, such as the common cold, flu, and chronic infections such as respiratory and lower urinary tract infections. In addition, there have been a few studies that support its use for chronic candidiasis. The active components of Echinacea are phenolic compounds, terpenoid compounds, nitrogenous compounds, such as alkylamides and alkaloids, and carbohydrates, such as polysaccharides. Polysaccharide components have been proven to activate macrophages (stimulation of phagocytosis), increase leukocyte mobility, and increase cellular respiration that may lead to the attack of tumor cells (increased tumor necrosis factor) and microorganisms (Cupp, 2000; Blumenthal et al., 2000; Rotblatt and Ziment, 2002).

Comments

Echinacea seems to be a good example of an herb that proves there is no such thing as a generic herbal medicine. The quality of Echinacea in studies has definitely had some influence on the confounding results of studies. As there are a number of pharmacologically important compounds in Echinacea, researchers should be careful to characterize the nature of their preparation. Likewise, consumers and health care professionals should be aware of the potential of buying poor quality product.

Scientific Support

The Common Cold and Flu

In a recent randomized, double-blind, placebo-controlled study on the efficacy of a standardized preparation of Echinacea purpurea (100 mg freeze-dried pressed juice from the aerial portion of the plant 3 times daily) on the severity and duration of the common cold. Of the 180 patients that were enrolled and given the active or placebo treatment, no statistical differences were found between groups in the total symptom scores, or mean individual scores, nor was there a difference noted in the times to resolution of symptoms (Yale and Liu, 2004).

In another recent randomized, double-blind, placebo-controlled study Echinacea was again studied to elucidate it effects on the common cold. The authors theorized that much of the inconclusive nature of the studies to date were due to the utilization of poorly standardized products that were devoid of active components. Therefore, they used a preparation that was standardized to alkamides (0.25 mg/ml), cichoric acid (2.5 mg/ml) and polysaccharides (25 mg/ml) (Echinilin, Natural Factors Nutritional Products, Inc.). The 282 healthy subjects were given either echinacea or placebo to take at the onset of the first symptom related to a cold, consuming 10 doses on day one, and 4 doses on the subsequent seven days. The total daily symptom scores were 23.1% lower in the Echinacea group than in the placebo, and the response rate was greater in this group throughout the study (Goel et al., 2004).

A randomized, double-blind placebo-controlled community-based trial was conducted to determine the efficacy of dried, encapsulated, whole plant Echinacea as early treatment for the common cold. The study concluded that compared with placebo, unrefined Echinacea provided no detectable benefit or harm for those who had the common cold. The study was designed with a power of 80% requiring 150 participants. The study enrolled 148 participants (Barrett et al., 2002).

In another randomized double-blind placebo-controlled study, researchers determined the efficacy of an Echinacea compound herbal tea preparation given at early onset of cold or flu symptoms. The study concluded that treatment with the Echinacea herbal tea was effective for relieving symptoms in a shorter period of time that a placebo. The placebo used was a different herbal tea marketed to promote healthy digestion and that should not have improved or worsened the common cold or flu symptoms (Lindenmuth and Lindenmuth, 2000).

Researchers of an another randomized placebo-controlled double-blind study wanted to determine the effect of fluid extract (Madaus AG, 4 mL twice daily for 8 weeks) of E. purpurea on the incidence and severity of colds and respiratory infections. The study concluded that treatment with fluid extract of E. purpurea did not significantly decrease the incidence, duration or severity of colds and respiratory infections compared to placebo when tested in 109 participants (Grimm and Muller, 1999).

Four types of Echinacea preparations were studied in 246 people who easily caught colds. The treatment groups were given: a) an E. purpurea crude extract consisting of 5% root and 95% above ground parts (Echinaforce®, 6.78 mg/tablet, two tablets, three times daily); b) the same extract at a higher dosage (48.27 mg/tablet, two tablets, three times daily); a unspecified crude extract of the root (E.purpurea, 29.60 mg/tablet, two tablets, three times daily); and d) placebo. The participants were instructed to start taking their medication as soon as they felt a cold coming on until it was finished (not to exceed 7 days). The placebo and treatment d) produced similar results; whereas, the a) and b) treatments produced an improvement of cold symptoms by 62.7% and 64%. The physicians found Echinacea preparations to be 70% effective, while the patients judged them to be 80% effective. The authors concluded that Echinacea was an effective and low-risk alternative for treating the symptoms of the common cold (Brinkeborn et al., 1999).

The expressed juice of the aerial parts of Echinacea purpurea (Echinagard®) was studied in a placebo-controlled study of 120 patients who presented with the first signs of the common cold. There was a highly significant decrease in the median time required before the patients improved in the treatment group vs. placebo (zero vs. five days); in those patients determined to have developed “real colds”, the difference between the treatment and placebo groups was 4 days vs. 8 days, respectively (Hoheisel et al., 1997).

An herbal formulation containing Echinacea purpurea root extract (25 mL), vitamin C (100 mg), fennel seed extract (10.3 mg), eucalyptus leaf extract (12.3 mg), and rosemary leaf extract (20.1 mg) was studied in 32 patients against the common cold. The other herbs in the formulation were added to provide expectorant and antiseptic properties. The groups were given 4 tablets of either placebo or the herbal formulation for 44 days, and evaluated based on the amount of discharge of the thin nasal mucus they produced and the number of tissues they used. The results of the groups were significantly different: the placebo group used a mean number of 1,168 tissues and recovered in 4.37±1.57 days, and the treatment group used 882 tissues and recovered in 3.37±1.25 days (Scaglione and Lund, 1995).

The expressed juice of Echinacea purpurea (Echinacin® 4 mL, twice daily for 8 weeks) vs. placebo was studied in 108 patients who had frequent cold infections. The patients who received the Echinacea treatment took a longer period of time until contracting the cold: 40 days for the treatment group vs. 25 days for the placebo. Also, 35.2% of the patients who received the treatment remained without infections vs. 25.9% of those who received placebo. The placebo group contracted infections that were more severe, and they also showed evidence of a weakened immune system (Schöneberger, 1992).

General Immune Function

A systematic review of the trials in which Echinacea was used as an immunomodulator (26 total) concluded Echinacea to be an effective immunomodulator. However, the authors also noted that the studies were not high quality, and they recommended more well designed clinical trials to better ascertain the doses for specific conditions and preparations (Melchart et al., 1994).

A study of the immunological changes produced by an extract of E. purpurea in 12 men found a 120% increased rate of granulocytic phagocytosis. This was compared against a placebo group which only showed a 30% increase over the same period of time. After cessation of treatment, phagocytosis decreased to normal levels in 3 days. No changes were found in the immunoglobulin and leukocyte levels, or the erythrocyte sedimentation rate (Jurcic et al., 1989).

Exercise-induced immunosuppression was studied in 42 male tri-athletes. Three groups comprising E. purpurea extract, magnesium supplement, and placebo treatments were formed and followed as the athletes underwent regular competitive sprint training. The magnesium and placebo treated groups gave similar results, but the Echinacea group exhibited significantly enhanced exercise-induced decrease in levels of soluble IL-2 receptor (sIL-2R), significantly greater exercise-induced levels of urine IL-6, and significantly greater exercise-induced increases in cortisol concentrations. It was noted that the most common reported cytokine responses to strenuous exercise are increased in the release of IL-6 and sIL-2R and IL-6 in the acute phase response to injury or infection. The absence of a significant decrease of NK cells in the Echinacea groups suggested a counter-effect of cortisol on these cells (Berg et al., 1998)

Safety / Dosage

Since there are many types of Echinacea preparations available, and several immunologically-active compounds in Echinacea, dosage recommendations are varying. In the United States, commercial extracts are typically standardized to the echinacosides and 4-sesquiterpene esters; however, it has been suggested that the caffeic acid derivatives (such as echinacoside and cichoric acid) and the polysaccharides, glycoproteins, alkamides and polyacetylenes make better standards. Some of the typical dosage recommendations are listed below (McKenna et al., 2002):

•Dried root or tea – 1-2 grams, three times daily;

•Freeze-dried plant – 325-650 mg, three times daily;

•Juice of aerial portions stabilized in 22% ethanol – 2-3 mL, three times daily;

•Tincture (1:5) – 3-4 mL, three times daily;

•Fluid extract (1:1) – 1-2 mL, three times daily;

•Solid dry extract (6.5:1 or 3.5% echinacoside) 100-250 mg, three times daily.

Chronic use of Echinacea is discouraged by some sources because it is believed to loose its effectiveness at boosting the immune system when needed during long-term usage(Chua, 2003). When used at the recommended doses, side-effects from taking Echinacea are rare, and there is little or no toxicity associated with its use. The LD50 of fresh-pressed E. purpurea juice in mice is 50 mL/kg, i.v.; and the polysaccharides of the aerial portions of the plant produced an LD50 of 1,000 to 2,500 mg/kg i.p in mice. Long term administration of the fresh-pressed juice also produced no toxic effects at many times the human dose; and no significant acute or subacute toxicity was found from oral administration of up to 15 g/kg and 8 g/kg, respectively (McKenna et al., 2002).

Echinacea may interfere with drugs that have immunosuppressant effects such as cyclosporine, and corticosteroids. In vitro studies showed inhibition of 3A4 enzyme activity of the CytochromeP450 system that would suggest possible interactions with lovastatin, ketoconazole, fexofenadine, and triazolam, etc. Those taking metronidazole or disulfram should avoid due to varying alcohol contents of Echinacea preparations. The use of acetaminophen, amiodarone, methotrexate, or ketoconazole with Echinacea may possibly increase the risk of hepatotoxicity (Abebe, 2002).

References

1.Abebe W Herbal Medication: Potential for Adverse Interactions with Analgesic Drugs. J Clin Pharm Ther. 2002; 27: 391-401.

2.Barrett BP, Brown RL, Locken K, Maberry R, Bobula JA, D’alessio D. Treatment of the Common Cold with Unrefined Echinacea: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Intern Med. 2002; 137: 939-946.

3.Berg, A.; H. Northoff; D. Konig et al. 1998. Influence of Echinacin (EC31) treatment on the exercise-induced immune response in athletes. Journal of Clinical Research 1:367-380.

4.Blumenthal M, Goldberg A, Brinckmann J, Foster S, editors. Herbal Medicine: Expanded Commission E Monographs. Massachusetts: Integrative Medicine Communications; 2000.

5.Brinkeborn, R.M.; D.V. Shah; and F.H. Degenring. 1999. Echinaforce® and other Echinacea fresh plant preparations in the treatment of the common cold. A randomized, placebo-controlled, double-blind clinical trial. Phytomedicine 6:1-5.

6.Chua D Chronic Use of Echinacea Should be Discouraged. Am Fam Physician. 2003; 68(4): 617.

7.Cupp MJ, editor. Toxicology and Clinical Pharmacology of Herbal Products. New Jersey: Humana Press; 2000.

8.Goel V, Lovlin R, Barton R, Lyon MR, Bauer R, Lee TD, Basu TK. Efficacy of a standardized echinacea preparation (Echinilin) for the treatment of the common cold: a randomized, double-blind, placebo-controlled trial. J Clin Pharm Ther. 2004 Feb;29(1):75-83.

9.Grimm W, Muller H. A Randomized Controlled Trial of the Effect of Fluid Extract of Echinacea Purpurea on the Incidence and Severity of Colds and Respiratory Infections. Am J Med. 1999; 106: 138-143.

10.Hoheisel, O.; M. Sandberg; S. Dertram et al. 1997. Echinagard treatment shortens the course of the common cold: a double-blind, placebo-controlled clinical trial. European Journal of Clinical Research 9:261-268.

11.Jurcic, K; D. Melchart; M. Holzmann et al. 1989. Zwei probandenstudien zur stimulierung der granulozytenphagozytose durch echinaceaextraktthalitige präparate Two studies on the stimulation of the phagocytosis of granulocytes by drug preparations containing extracts of Echinacea in healthy volunteers. Zeitschrift für Phytotherapie 10: 67-70.

12.Lindenmuth GF, Lindemuth EB. The Efficacy of Echinacea Compound Herbal Tea Preparation on the Severity and Duration of Upper Respiratory and Flu Symptoms: A Randomized, Double-Blind Placebo-Controlled Study. J Altern Complement Med. 2000; 6(4): 327-334.

13.McKenna, D.J.; K. Jones; K. Hughes (eds). 2002.. Botanical Medicines: The Desk Reference for Major Herbal Supplements. Haworth Press: Bimhington, New York.

14.Melchart, D.; K. Linde; F. Worku et al. 1994. Immunomodulation with Echinacea – a systematic review of controlled clinical trials. Phytomedicine 1:245-254.

15.Rotblatt M, Ziment I. Evidenced-Based Herbal Medicine. Philadelphia: Hanley& Belfus; 2002.

16.Scaglione, F.; and B. Lund. 1995. Efficacy in the treatment of the common cold of a preparation containing an Echinacea extract. International Journal of Immunotherapy 11:163-166.

17.Schöneberger, D. 1992. The influence of immunostimulating effects of pressed juice from Echinacea purpurea on the course and severity of colds. Results of a double-blind study. Forum Immunologie 8: 2-12.

18.Yale SH, Liu K.Echinacea purpurea therapy for the treatment of the common cold: a randomized, double-blind, placebo-controlled clinical trial. Arch Intern Med. 2004 Jun 14;164(11):1237-41.

EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.