Formula 702.     120 tablets.   Total of 4 each day with meals.

Price range: 1-2 containers: $22.95 each.   3-5: $21.95.   6+: $20.95

Fatigue Relief works by providing the body with a basic blend of vitamins and minerals which are often missing in the typical American diet. 

Added to this multivitamin is a proprietary blend of herbs and other compounds which have been shown to reduce the symptoms of fatigue, including immune system weakness, a decrease in mental function, and low physical energy.

 

 

INGREDIENTS LIST (Click here.)

 

 

 

For more information and research on the ingredients in the vitamin and mineral base, see the appendices.

 
This proprietary blend contains several important ingredients: 

Goldenseal root is often combined with echinacea to boost the immune system.  The active component of goldenseal is berberine, a substance which fights infections and which is used in Chinese herbal medicine to treat upset stomach and diarrhea.  By assisting the body in digestion and immune response, goldenseal, combined with echinacea, helps relieve the immune system’s weakness as a result of fatigue.

Shiitake mushrooms are used as a treatment for hepatitis B, HIV, and stomach cancers, among other conditions.  The key compound of Shiitake mushrooms is called lentinan.  Lentinan helps the immune system by activating the body’s T cells, white blood cells produced by the Thymus and essential to the immune response.  Combined with raw Thymus concentrate, these two ingredients provide healthy assistance to the immune system.

German Chamomile belongs to the same family as echinacea, and it provides many of the same benefits.  Chamomile is generally used to treat upset stomach and upper respiratory infections, but it has been used to treat a variety of other conditions as well.  Importantly, chamomile is traditionally used to treat insomnia, menstrual cramps, and tension.  Chamomile can thus help to relieve some of the anxieties of fatigue.

Burdock root is known to herbalists as the most effective blood purifier.  Research indicates that burdock root may have anti-microbial properties; this would explain its reputation for clearing the bloodstream of harmful toxins.
 
Licorice is used primarily to treat stomach ulcers and bronchitis, but it is also used as a soothing agent.  Recent studies suggest that licorice may prevent the spread of cancer cells in patients with breast cancer (see research summaries below). 

Ligusticum porteri, also known as osha, is most often used to treat cold symptoms.  It has a soothing effect on the throat and also alleviates indigestion.  When fatigue starts to wear on the immune system, common cold and flu viruses have a better chance of attacking the body, but supplements like ligusticum porter can help prevent this breakdown from occurring.

Along with lowering blood pressure and increasing endurance, astragalus is used in chemotherapy patients to fight symptoms of immune deficiency.  In people with severe heart disease, astragalus may have antioxidant benefits.  Traditionally, astragalus is recommended for patients with chronic infections or cold symptoms.

Lomatium dissectum is an herbal remedy shown to have some effect on a variety of viral and bacterial infections, including Hepatitis C, influenza, AIDS, HIV, chronic fatigue, bronchitis, sinusitis, and colds.

Malic acid, when combined with magnesium, may be an effective treatment for fibromyalgia, a fatigue syndrome whose symptoms include nerve pain, tingling in the muscles, acute muscle or bone pain, and sensitivity of the skin.

The other components of the proprietary blend: raw adrenal concentrate, raw Thymus concentrate, N-Acetyl-L-Cysteine, Cysteine, L-Methionone, and Glutamic acid are all common supplements which improve the body’s ability to use energy effectively.  N-Acetyl-L-Cysteine is an antioxidant which works with the immune system.  Cysteine assists the body in creating L-Taurine, an important acid for the nervous system and a component of popular energy drinks such as Red Bull. 

Acting with the proprietary blend and the multi-vitamin support are the final contents of this formula: choline, inositol, PABA, Vanadium, and Boron. Choline and inositol provide support to cognitive function.  PABA is a food for bacteria and is for that reason sometimes used to assist the bacteria of the intestinal tract, thereby aiding digestion.  Vanadium is a trace element used to enhance athletic performance and to treat bipolar disorder.

Fatigue Relief is a carefully balanced formula designed to treat the symptoms of fatigue.  The components of this supplement are essential vitamins and minerals and a blend of herbs which have been shown to boost the immune system, increase endurance, and sharpen cognitive function.  

 

 

 

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STUDIES & CITATIONS:



Goldenseal:

“Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components.”
Author:                       Chatterjee,-P; Franklin,-M-R
Citation:         Drug-Metab-Dispos. 2003 Nov; 31(11): 1391-7
Abstract:        The concurrent use of herbal medicinals with prescription and over-the-counter drugs carries a risk for unanticipated adverse drug-botanical pharmacokinetic interactions, particularly as a result of cytochrome P450 (P450) inhibition. Extracts of goldenseal (Hydrastis canadensis) containing approximately equal concentrations ( approximately 17 mM) of two methylenedioxyphenyl alkaloids, berberine and hydrastine, inhibited with increasing potency (CYP2C9) diclofenac 4'-hydroxylation, (CYP2D6) bufuralol 1'-hydroxylation, and (CYP3A4) testosterone 6beta-hydroxylation activities in human hepatic microsomes. The inhibition of testosterone 6beta-hydroxylation activity was noncompetitive with an apparent Ki of 0.11% extract. Of the methylenedioxyphenyl alkaloids, berberine (IC50 = 45 microM) was the more inhibitory toward bufuralol 1'-hydroxylation and hydrastine (IC50 approximately 350 microM for both isomers), toward diclofenac 4'-hydroxylation. For testosterone 6beta-hydroxylation, berberine was the least inhib itory component (IC50 approximately 400 microM). Hydrastine inhibited testosterone 6beta-hydroxylation with IC50 values for the (+)- and (-)-isomers of 25 and 30 microM, respectively. For (-)-hydrastine, an apparent Ki value of 18 microM without preincubation and an NADPH-dependent mechanism-based inhibition with a kinactivation of 0.23 min(-1) and a KI of approximately 110 microM were determined. Cytochrome P450 metabolic-intermediate (MI) complex formation could be demonstrated for both hydrastine isomers. With expressed P450 isoforms, hydrastine formed a P450 MI complex with CYP2C9, CYP2D6, and CYP3A4. Coexpression of cytochrome b5 with the P450 isoforms enhanced the rate but not the extent of P450 MI complex

“A reproductive screening test of goldenseal.”
Author:                       Yao,-M; Ritchie,-H-E; Brown-Woodman,-P-D
Citation:         Birth-Defects-Res-B-Dev-Reprod-Toxicol. 2005 Oct; 74(5): 399-404

BACKGROUND: Goldenseal (Hydrastis canadensis L) is a multi-purpose herb (Hobbs, 1990: Pharm Hist 32:79-82) widely used for its antibiotic properties. It is traditionally contraindicated in pregnancy based on in vivo data but this contraindication has not been confirmed by conventional studies that have been peer reviewed.

METHODS: Female rats were dosed by gavage using 65 times the human dose of goldenseal daily on either gestation days (GD) 1-8 or GD 8-15. Controls received an equivalent dose of ethanol. On GD 20, fetuses were weighed and examined for signs of external, internal, or skeletal malformations. Rat fetuses were also explanted on GD 10.5 and cultured with decreasing concentrations of goldenseal for 26 hr. Embryos were examined for growth retardation and malformations.

RESULTS: There was no increase in pre- or post-implantation losses. There was no increase in fetal body weight in fetuses exposed to goldenseal. There was no difference in incidence of external or internal malformations. Goldenseal induced toxicity when GD10.5 embryos were cultured for 26 hr in rat serum to which extract was added.

CONCLUSIONS: It is likely that poor absorption of goldenseal from the small intestine could explain the discrepancy between the in vivo and in vitro results. It is unlikely that serum concentration from oral treatment could attain the LOEL achieved in vitro. The contrasting results highlight the continuing importance of in vivo work and the necessity of pharmacokinetic data when interpreting in vitro data. The data suggest that goldenseal, at the prescribed human dose, is unlikely to be absorbed to an extent to be unsafe to use in pregnancy despite the apparent cytotoxic effects in vitro. However, these results indicate that pharmacokinetic studies are required to confirm this conclusion. Copyright 2005 Wiley-Liss, Inc.

“Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.). 2. Palmatine, hydrastine, canadine, and hydrastinine.”
Author:                       Inbaraj,-J-J; Kukielczak,-B-M; Bilski,-P; He,-Y-Y; Sik,-R-H; Chignell,-C-F
Citation:         Chem-Res-Toxicol. 2006 Jun; 19(6): 739-44
Abstract:        Goldenseal is an herb that is widely used in dietary supplements, eye washes, and skin lotions. The presence of Goldenseal root powder in dietary supplements and the topical application of Goldenseal preparations raise the possibility that an adverse phototoxic reaction may result from an interaction between its constituent alkaloids and light in exposed tissues. We have previously shown that berberine, the major alkaloid in Goldenseal powder, in combination with UVA causes DNA damage and cell death in HaCaT keratinocytes [(2001) Chem. Res. Toxicol. 14, 1529]. We have studied the photochemical and photobiological properties of four minor alkaloids found in Goldenseal, namely, hydrastine, palmatine, canadine, and hydrastinine. UVA radiation of palmatine in aqueous solutions generated no (1)O(2), but in CH(2)Cl(2), copious amounts of (1)O(2) were detected (Phi = 0.2). Palmatine also photogenerated oxygen-centered radicals, (*)OH and O(2)(*)(-) in aerated aqueous buffer and acetonitrile, respectively, as detected by the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). In nitrogen-sparged acetonitrile containing DMPO, we observed the neutral palmatine radical formed by one-electron reduction. UVA irradiation (4 J/cm(2)) of HaCaT keratinocytes in the presence of palmatine (50 microM) resulted in a 50% decrease in cell viability but no DNA damage as measured by the comet assay. UVA irradiation of hydrastine, hydrastinine, or canadine (50 microM) did not cause DNA damage or cell death in keratinocytes. Although palmatine is photoactive, it is present in such small amounts in Goldenseal root powder that the phototoxicity of the herb is most likely due to berberine, the major constituent alkaloid.



ECHINACEA

Research:


Title:                 Echinacea in the prevention of induced rhinovirus colds: a meta-analysis.
Author:                       Schoop,-R; Klein,-P; Suter,-A; Johnston,-S-L
Citation:         Clin-Ther. 2006 Feb; 28(2): 174-83
Abstract:        BACKGROUND: The therapeutic effectiveness of Echinacea in the treatment and the prevention of colds has been debated. Studies of naturally occurring colds are hampered by variability in time from onset of symptoms to treatment and by heterogeneity in trial design. Experimental infection studies allow for the standardization of time to initiation of treatment, virus type and dose, and immune competence of volunteers. OBJECTIVE: To determine whether the negative results obtained in previous studies of Echinacea were a consequence of efficacy or of inadequate sample size, we performed a meta-analysis of experimental rhinovirus infection studies on the efficacy of Echinacea extracts to prevent symptomatic development of an experimentally induced cold. METHODS: We carried out a systematic search of English- and German-language literature using the MEDLINE, EMBASE, CAplus, BIOSIS, CABA, AGRICOLA, TOXCENTER, SCISEARCH, NAHL, and NAPRALERT, databases and the search terms Echinacea, black Sampson, coneflower, and Roter Sonnenbut. Matching documents were then searched for > or = 1 of the following terms: rhinovirus, RV, inoculation, Inokulation, induced, induziert, artificial, and artifiziell. Suitable studies were identified and pooled for analysis. The primary end point was the development of symptomatic clinical colds, as defined by the authors of the original studies. Results were reported as differences in the proportion of subjects with symptomatic episodes of a common cold, expressed as odds ratios (ORs) and 95% CIs. The secondary outcome was the difference in total symptom severity scores between treatment groups (assessed daily by integrating the severity scores of 8 individual cold-related symptoms that were rated on a scale from 0 [absent] to 4 [very severe]). RESULTS: A total of 234 articles were identified through the literature search; 231 were excluded from the analysis because they related to studies of spontaneous common colds. Three suitable studies were selected for pooling of data. Based on the analysis, the likelihood of experiencing a clinical cold was 55% higher with placebo than with Echinacea (OR, 1.55 [95% CI, 1.02-2.36]; P<0.043). The absolute difference in total symptom scores between groups was -1.96 (95% CI, -4.83 to 0.90; P=NS). CONCLUSIONS: This meta-analysis suggests that standardized extracts of Echinacea were effective in the prevention of symptoms of the common cold after clinical inoculation, compared with placebo. Further prospective, appropriately powered clinical studies are required to confirm this finding.


Title:                 Can Nutrition Limit Exercise-Induced Immunodepression?
Author:           Gleeson,-M
Citation:         Nutrition-reviews. 2006 Mar; 64(3): 119-131.
Abstract: Prolonged exercise and heavy training are associated with depressed immune cell function. To maintain immune function, athletes should eat a well-balanced diet sufficient to meet their energy, carbohydrate, protein, and micronutrient requirements. Consuming carbohydrate during prolonged strenuous exercise attenuates rises in stress hormones and appears to limit the degree of exercise-induced immune depression. Recent evidence suggests that antioxidant vitamin supplementation may also reduce exercise stress and impairment of leukocyte functions. Further research is needed to evaluate the effects of other antioxidants and dietary immunostimulants such as probiotics and echinacea on exercise-induced immune impairment.


A proprietary extract from the echinacea plant (Echinacea purpurea) enhances systemic immune response during a common cold.
Author:           Goel,-V; Lovlin,-R; Chang,-C; Slama,-J-V; Barton,-R; Gahler,-R; Bauer,-R; Goonewardene,-L; Basu,-T-K
Citation:         Phytother-Res. 2005 Aug; 19(8): 689-94
Abstract:        In a previous paper, it was reported that Echinilin (Factors R & D Technologies, Burnaby, British Columbia, Canada) a formulation prepared from freshly harvested Echinacea purpurea plants and standardized on the basis of three known active components (alkamides, cichoric acid and polysaccharides) is effective for the treatment of a naturally acquired common cold. However, the mechanism by which this effect is achieved remains unknown. In the present study, Echinilin or placebo were administered to volunteers at the onset of their cold for a period of 7 days, with eight doses (5 mL/dose) on day 1 and three doses on subsequent days. Fasting blood samples were obtained before and during their colds. The decrease in total daily symptomatic score was more evident in the echinacea group than in the placebo group. These effects of echinacea were associated with a significant and sustained increase in the number of circulating total white blood cells, monocytes, neutrophils and NK cells. In the later part of the cold, the echinacea treatment suppressed the cold-related increase in superoxide production by the neutrophils. These results suggest that Echinilin, by enhancing the non-specific immune response and eliciting free radical scavenging properties, may have led to a faster resolution of the cold symptoms. Copyright (c) 2005 John Wiley & Sons, Ltd.


Enhancement of natural killer cells and increased survival of aging mice fed daily Echinacea root extract from youth.
Author:           Brousseau,-M; Miller,-S-C
Citation:         Biogerontology. 2005; 6(3): 157-63
Abstract:        In spite of Echinacea-based products being among the best-selling herbs in the world to date, to allay assorted ailments, the debate is still on-going with respect to the efficacy of ingesting the herb intermittently, continuously, or only at the beginning of an affliction. We sought, therefore, to find out if mice, receiving dietary Echinacea daily, throughout life, from youth until late middle-age, demonstrated any longevity/survival differences, and/or any differences in their various populations of immune/ hemopoietic cells. Sustained and/or high levels of these cells are crucial for longevity. Some mice were maintained on a regular chow diet to which was added Echinacea purpurea daily (2 mg/mouse), from puberty (7 week) until just beyond 13 months of age (late middle-age in mice). Control mice, identically housed and maintained, received identical chow without the herb. Mice consuming untreated diet had a 79% survival by 10 months of age, while those consuming Echinacea daily in the diet were still 100% alive by 10 months. At approximately 13 months of age, mice consuming untreated diet had a 46% survival rate while those consuming Echinacea, were 74% alive at this time. Moreover, the key immune cells, acting as the first line of defense against developing neoplasms in mice and humans, i.e., natural killer (NK) cells, were significantly elevated in absolute number both in their bone marrow production site, as well as in the major organ to which they traffic and function, i.e., the spleen. The cells of the myeloid/granulocyte lineages remained steadfastly at control levels in both the bone marrow and spleen in Echinacea-consuming mice. Thus, it appears that regular intake of Echinacea may indeed be beneficial/prophylactic, if only for the reason that it maintains in an elevated state NK cells, prime elements in immune surveillance against spontaneous-developing tumors, a phenomenon which increases in frequency with progressive aging.

Report from The National Institutes Of Health And The U.S. National Library Of Medicine:

Echinacea species are perennials which belong to the Aster family and which originate in eastern North America. Traditionally used for a range of infections and malignancies, the roots and herb (above ground parts) of echinacea species have attracted recent scientific interest due to purported "immune stimulant" properties. Oral preparations are popular in Europe and the United States for prevention and treatment of upper respiratory tract infections (URI), and  Echinacea purpurea  herb is believed to be the most potent echinacea species for this indication. In the U.S., sales of echinacea are believed to represent approximately 10% of the dietary supplement market.

For URI treatment, numerous human trials have found echinacea to reduce duration and severity, particularly when initiated at the earliest onset of symptoms. However, the majority of trials, largely conducted in Europe, have been small or of weak design. Negative results exist of a U.S. trial in adults, which used a whole-plant echinacea preparation containing both  E. purpurea  and  E. angustifolia . Another clinical trial reported in July 2005 did not demonstrate any clinical benefit either. However, a 2006 meta-analysis investigating the efficacy of echinacea found that the likelihood of experiencing a clinical cold was 55% higher with placebo than with Echinacea (based on three trials). The sum of the current is conflicting and further well-designed studies are needed before a definitive conclusion can be drawn. Lack of benefit in children ages 2-11 has also been reported.

References:
Ang-Lee M, Moss J, Yuan C. Herbal medicines and perioperative care. JAMA. 2001;286(2):208-216.

Barrett B, Kiefer D, Rabago D. Assessing the risks and benefits of herbal medicine: an overview of scientific evidence. [Review]. Altern Ther Health Med. 1999;5(4):40-49.

Barrett B, Vohmann M, Calabrese C. Echinacea for upper respiratory infection. J Fam Pract. 1999;48:628-635.

Blumenthal M, Goldberg A, Brinckmann J. Herbal Medicine: Expanded Commission E Monographs. Newton, MA: Integrative Medicine Communications; 2000:88-102.

Borchers AT, Keen CL, Stern JS, Gershwin ME. Inflammation and Native American medicine: the role of botanicals. [Review]. Am J Clin Nutr. 2000 Aug;72(2):339-347.

Brinkeborn RM, Shah DV, Degenring FH. Echinaforce and other Echinacea fresh plant preparations in the treatment of the common cold. A randomized, placebo controlled, double-blind clinical trial. Phytomedicine. 1999;6(1):1-6.

Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications; 1998:67-69.

ConsumerLab.com. Product review: echinacea. Accessed at: http://www.consumerlab.com/results/echinacea.asp on April 1, 2002.

Ernst E. The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John's Wort,

Ginseng, Echinacea, Saw Palmetto, and Kava. [Review]. Ann Intern Med. 2002;136(1):42-53.

Frank LG. 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 Comp Alt Med. 2000;6(4):327-334.

Gallo M, Sarkar M, Au W, et al. Pregancy outcome following gestational exposure to echinacea. Arch Intern Med. 2000; 160:3141-3143.

Lindenmuth GF, Lindenmuth 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.

Mahady GB. Echinacea: recommendations for its use in prophylaxis and treatment of upper respiratory tract infections. Nutr Clin Care. 2001;4(4):199-208.

Melchart D, Walther E, Linde K, Brandmaier R, Lersch C. Echinacea root extracts for the prevention of upper respiratory tract infections: a double-blind, placebo-controlled randomized trial. Arch Fam Med. 1998;7:541–545.

Melchart D, Linde K, Fischer P, Kaesmayr J. Echinacea for preventing and treating the common cold. [Review]. Cochrane Database Syst Rev. 2000;(2):CD000530.

Melchart D, Linde K, Worku F, Sarkady L, Holzmann M, Jurcic K, et al. Results of five randomized studies on the immunomodulatory activity of preparations of echinacea. J Alt Comp Med. 1995;1(2):145–160.

Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158(20):2200–2211.

Mullins RJ, Heddle R. Adverse reactions associated with echinacea: the Australian experience. Ann Allergy Asthma Immunol. 2002;88(1):42-51.

O'Hara M, Kiefer D, Farrell K, Kemper K. A review of 12 commonly used medicinal herbs. Arch Fam Med. 1998;7(6):523-536.

Percival SS. Use of echinacea in medicine. [Review]. Biochem Pharmacol. 2000;60(2):155-158.

Rotblatt M, Ziment I. Evidence-Based Herbal Medicine. Philadelphia, PA: Hanley & Belfus, Inc; 2002:160-165.

Soon SL, Crawford RI. Recurrent erythema nodosum associated with Echinacea herbal therapy. J Am Acad Dermatol. 2001;44(2):298-299.

Turner RB, Riker DK, Gangemi JD. Ineffectiveness of Echinacea for prevention of experimental rhinovirus colds. Antimicrob Agents Chemother. 2000;44:1708-1709.

White L, Mavor S. Kids, Herbs, Health. Loveland, Colo: Interweave Press; 1998:22, 28-29.

Shiitake Mushrooms:

 “Augmentation of lymphokine-activated killer cell activity by lentinan.”
Author:           Tani, M : Tanimura, H : Yamaue, H : Tsunoda, T : Iwahashi, M : Noguchi, K : Tamai, M : Hotta, T : Mizobata, S
Citation:         Anticancer-Res. 1993 Sep-Oct; 13(5C): 1773-6
Abstract:        Lymphokine-activated killer (LAK) activity stimulated by interleukin 2 (IL-2) and/or lentinan was examined in the peripheral blood of 9 healthy subjects and 7 cancer patients. After 4 and 8 days culture, LAK killer activity stimulated by IL-2 and lentinan against autologous tumor and K562 cells was greater than that stimulated by IL-2 alone. The optimal concentration of lentinan for the generation of killer cells ranged from 25-500 ng/ml, a level which can be achieved in vivo by the administration of clinical doses of this agent. The expression of CD25 antigen, the alpha chain of the IL-2 receptor on the activated killer cells was increased by lentinan. Thus it was shown that LAK cells stimulated with IL-2 plus lentinan had strong cytotoxicity and might be useful as effector cells for adoptive immunotherapy.

 “Individual diversity of IL-6 generation by human monocytes with lentinan administration.”
Author:           Sakamaki, S : Kohgo, Y : Suzuki, M : Ogiwara, R : Suga, T : Kondo, N : Izawa, M : Kanisawa, Y : Niitsu, Y
Citation:         Int-J-Immunopharmacol. 1993 Aug; 15(6): 751-6
Abstract:        Effect of in vivo administration of lentinan on IL-6 generation by human peripheral blood monocytes was examined using 5 healthy volunteers. Monocytes isolated from them before and 3 days after intravenous administration of 2 mg lentinan per person were cultured for 2 days and then the levels of IL-6 in the supernatants of cultured monocytes were determined. In vivo lentinan administration elicited an increase in IL-6 generation by monocytes in 3 of 5 cases. Failure to increase IL-6 generation by monocytes in two cases is characteristic of lentinan, since these monocytes generated an apparent level of IL-6 in response to lipopolysaccharide, a potent monocyte activator. Thus, it was demonstrated that lentinan was capable of augmenting IL-6 generation by human monocytes and that there was individual difference in their responsiveness to lentinan.

 “Lentinan potentiates immunity and prolongs the survival time of some patients.”
Author:                       Matsuoka, H : Seo, Y : Wakasugi, H : Saito, T : Tomoda, H
Citation:         Anticancer-Res. 1997 Jul-Aug; 17(4A): 2751-5
Abstract:        For the selection of patients responding well to lentinan, we performed two immunological analysis of patients. Flow cytometric analysis was obtained from peripheral blood lymphocytes; the patients who had greater than 2.5 ratio of [CD11(-) CD8(+)/CD11(+) CD8(+) after treatment]/[CD11(-) CD8(+)/CD11(+) CD8(+) before treatment] at 10 days after lentinan administration showed prolonged survival. The analysis of the- levels of soluble factors such as IL-6, sIL-6R, TNF-alpha, G-CSF, sICAM-1, IAP, and PGE2 and the decreasing levels of G-CSF, IL-6, and PGE2 after lentinan administration had a statistically significant correlation with the ratio of [CD4(+) CD29(+)/CD4(+) CD29(-) after treatment]/[(CD4(+) CD29(+)/CD4(+)CD29(-) before treatment]. The decrease in IL-6, G-CSF, and PGE2 levels after lentinan administration indicated an increase in immunine potential. From these results, we belive that patients with over 2.5-fold increase in [CD11(-) CD8(+)/CD11(+) CD8(+) after treatment]/[CD11(-) CD8(+)/CD11(+) CD8(+) before treatment] and showing a decrease in IL-6, G-CSF, and PGE2 levels after lentinan administration should continue treatment with lentinan for a long period.

 “Immunoregulatory effects of the antitumor polysaccharide lentinan on Th1/Th2 balance in patients with digestive cancers.”
Author:           Yoshino, S : Tabata, T : Hazama, S : Iizuka, N : Yamamoto, K : Hirayama, M : Tangoku, A : Oka, M
Citation:         Anticancer-Res. 2000 Nov-Dec; 20(6C): 4707-11

BACKGROUND: Recent studies demonstrated that patients with advanced cancer may have impaired cell-mediated immunity caused by an imbalance between Th1 and Th2 responses. We evaluated the ability of lentinan (LNT) to modulate Th1 and Th2 responses in patients with digestive cancers.

METHODS: Peripheral blood samples were collected preoperatively from 28 patients with digestive cancers before and after intravenous administration of LNT (2 mg x 3 times/week). The proportions of CD4+ T-cells producing intracellular cytokines were determined with flow cytometry.

RESULTS: After LNT treatment, CD4+ IFN-gamma+ T-cell percentages increased significantly (p less than 0.05), whereas CD4+ IL-4+ T-cell and CD4+ IL-6+ T-cell percentages decreased significantly (p less than 0.02). No significant change occurred in proportions of CD4+ IL-10+ T-cells. The after/before LNT treatment percentages ratio of CD4+ IFN-gamma+ T-cells correlated negatively with that of CD4+ IL-4+ T-cells (p less than 0.01). The after/before treatment percentage ratio of CD4+ IL-4+ T-cells correlated positively with that of CD4+ IL-6+ T-cells (p less than 0.05).

CONCLUSION: LNT apparently can cancel Th2-dominant condition in patients with digestive cancers and may improve the balance between Th1 and Th2.

Chamomile:

“Inhibitory effect of chamomile essential oil on the sister chromatid exchanges induced by daunorubicin and methyl methanesulfonate in mouse bone marrow.”
Hernandez Ceruelos, A : Madrigal Bujaidar, E : de la Cruz, C
Toxicol-Lett. 2002 Sep 5; 135(1-2): 103-110
Different preparations of chamomile (Matricaria chamomilla) are used to treat various diseases, including inflammation and cancer; however, no studies on the plant's antigenotoxic capacity have been made. The aim of the present work was to determine the inhibitory effect of the chamomile essential oil (CO), on the sister chromatid exchanges (SCEs) produced by daunorubicin and methyl methanesulfonate (MMS) in mouse bone marrow cells. CO was analyzed and was found to contain 13 compounds, mainly bisabolol and its oxides, chamazulene, farnesene, germacrene and other sesquiterpenes. Initially, a toxic and a genotoxic analysis of CO were made; both showed negative results.

To determine whether CO can inhibit the mutagenic effects induced by daunorubicin, one group of mice was administered corn oil, another group was treated with the mutagen (10 mg/kg), a third group was treated with 500 mg/kg of CO; three other groups were treated first with CO (5, 50 and 500 mg/kg) and then with 10 mg/kg of daunorubicin. In the case of MMS, the experimental groups consisted of the following: the negative control group which was administered corn oil, a group treated with 25 mg/kg of MMS, a group treated with 1000 mg/kg of CO, and three groups treated first with CO (250, 500 and 1000 mg/kg) and then with MMS (25 mg/kg). The results indicated a dose-dependent inhibitory effect on the SCEs formed by both mutagens. In the case of daunorubicin, a statistically significant result was observed in the three tested doses: from the lowest to the highest dose, the inhibitory values corresponded to 25.7, 63.1 and 75.5%.

No alterations were found with respect to the cellular proliferation kinetics, but a reduction in the mitotic index was detected. As regards MMS, the inhibitory values were 24.8, 45.8 and 60.6%; no alterations were found in either the cellular proliferation kinetics or in the mitotic indices. Our results suggest that CO may be an effective antimutagen that could be considered for further study.

“Modulation of lipopolysaccharide-induced proinflammatory cytokine production in vitro and in vivo by the herbal constituents apigenin (chamomile), ginsenoside Rb(1) (ginseng) and parthenolide (feverfew).”
Smolinski,-A-T; Pestka,-J-J
Food-Chem-Toxicol. 2003 Oct; 41(10): 1381-90
Dietary supplements are not subject to the same pre-market approval as conventional drugs, thus the true efficacy and, in cases, safety of these products is not known. The objective of this study was to evaluate the potential anti-inflammatory properties of three herbal constituents, apigenin (chamomile), ginsenoside Rb(1) (ginseng) and parthenolide (feverfew) on lipopolysaccaharide (LPS)-induced proinflammatory cytokine production, and to determine if effects in cell culture could predict results in an intact animal model. Murine macrophage cells and mice were treated with the stimulant LPS and herbal constituents, and resultant culture supernatant and serum, respectively, were evaluated for interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha by ELISA. All three constituents inhibited LPS-induced IL-6 and/or TNF-alpha production in culture. Inhibition of these two cytokines was observed in mice, but did not display the same patterns of inhibition as cell culture data. The results suggest that all three constituents possessed anti-inflammatory properties, but that cell culture data can only be used to approximate potential effects in animals, and must be confirmed using appropriate animal models.

“Dietary intake of the flower extracts of German chamomile (Matricaria recutita L.) inhibited compound 48/80-induced itch-scratch responses in mice.”
Kobayashi,-Y; Nakano,-Y; Inayama,-K; Sakai,-A; Kamiya,-T
Phytomedicine. 2003 Nov; 10(8): 657-64
The antipruritic effects of the diets containing German chamomile on the compound 48/80-induced scratching in ddY mice were examined. Since it is reported that an injection of compound 48/80, but not histamine, induced scratching behaviour due to itch but not to pain in ddY mice (Kuraishi et al., 1995), compound 48/80-induced scratching in ddY mice seems to be a suitable parameter for evaluating antipruritic agents independent of histamine receptor antagonism. In the mice fed the diet containing 1.2 w/w % of the ethyl acetate extract of dried flower of German chamomile (Matricaria recutita L.) for 11 days, the compound 48/80-induced scratching behaviour was significantly suppressed. The ethyl acetate extract of German chamomile dose dependently suppressed compound 48/80-induced scratching without affecting body weight increase. The ethyl acetate fraction of the ethanol extract and the ethanol extract of hot water extraction residue of German chamomile flower also showed strong inhibition on the compound 48/80 -induced scratching. The inhibitory effects of the dietary intake of the German chamomile extracts on compound 48/80-induced itch-scratch response were comparable to oxatomide (10 mg/kg, p.o.), an anti-allergic agent.

“Antipruritic effect of the single oral administration of German chamomile flower extract and its combined effect with antiallergic agents in ddY mice.”
Kobayashi,-Y; Takahashi,-R; Ogino,-F
J-Ethnopharmacol. 2005 Oct 3; 101(1-3): 308-12
The single peroral administration of the ethyl acetate extract or essential oil of German chamomile (Matricaria recutita L.) showed remarkable antipruritic effects in the compound 48/80-induced itch-scratching test in ddY mice, if suitable vehicle was used. The ethyl acetate extract or essential oil of German chamomile dissolved in the vehicle of 10% ethanol, 10% Tween 80 and 80% physiological saline was orally administrated 2 h before pruritus provocation by compound 48/80 subcutaneous injection. The ethyl acetate extract or essential oil of German chamomile showed significant dose-dependent inhibition of the compound 48/80-induced scratching without affecting spontaneous motor activity. The antipruritic effects of antihistamine H1 antagonists, oxatomide (10 mg/kg) and fexofenadine (10 mg/kg), were only partial in this test. However, the antipruritic effects of these agents were remarkably enhanced by the combined administration of the ethyl acetate extract of German chamomile (300 mg/kg). Thus, the co-medication with the ethyl acetate extract, or essential oil of German chamomile and antihistamines might be effective for the pruritus which could not be perfectly resolved alone by conventional antihistamines.

“Hypnotic activities of chamomile and passiflora extracts in sleep-disturbed rats.”
Shinomiya,-K; Inoue,-T; Utsu,-Y; Tokunaga,-S; Masuoka,-T; Ohmori,-A; Kamei,-C
Biol-Pharm-Bull. 2005 May; 28(5): 808-10
In the present study, we investigated hypnotic activities of chamomile and passiflora extracts using sleep-disturbed model rats. A significant decrease in sleep latency was observed with chamomile extract at a dose of 300 mg/kg, while passiflora extract showed no effects on sleep latency even at a dose of 3000 mg/kg. No significant effects were observed with both herbal extracts on total times of wakefulness, non-rapid eye movement (non-REM) sleep and REM sleep. Flumazenil, a benzodiazepine receptor antagonist, at a dose of 3 mg/kg showed a significant antagonistic effect on the shortening in sleep latency induced by chamomile extract. No significant effects were observed with chamomile and passiflora extracts on delta activity during non-REM sleep. In conclusion, chamomile extract is a herb having benzodiazepine-like hypnotic activity

“Double-blind, randomized evaluation of clinical efficacy and tolerability of an apple pectin-chamomile extract in children with unspecific diarrhea.”
Becker,-B; Kuhn,-U; Hardewig-Budny,-B
Arzneimittelforschung. 2006; 56(6): 387-93

BACKGROUND: Acute diarrhea is one of the most common childhood diseases. The main aim of therapy is oral rehydration, mostly using a glucose-electrolyte solution. Results from a previous study (DIALOG I) investigating adjuvant treatment with a medicinal preparation containing an apple pectin-chamomile extract (Diarrhoesan) indicated a significantly reduced duration of diarrhea in children.

OBJECTIVES: The objective of the present clinical placebo-controlled, double-blind study (DIALOG II) was to assess the clinical efficacy and tolerability of the apple pectin-chamomile extract on a larger number of patients.

METHODS: The investigation was designed as a multicenter, randomized, double-blind, placebo-controlled parallel study enrolling 255 patients presenting with acute diarrhea. Patients were aged between 6 months and 6 years and treated on an outpatient basis with either an apple pectin-chamomile preparation or placebo. As a basic medication, each child received a glucose-electrolyte solution on the first day of treatment.

RESULTS: The primary outcome (primary efficacy parameter) included a combined analysis of stool frequency, stool The statistical analysis revealed a superior efficacy of the tested preparation over placebo with a significantly reduced stool frequency in the treatment group compared to the control group. The results were corroborated by efficacy assessment performed by investigators and patients. Treatment was well tolerated, with an incidence of adverse effects similar to placebo.

CONCLUSION: These findings support the concept of a beneficial influence of the investigated vegetable extract in shortening the course of the disease and relieving associated symptoms.

Burdock root:

“Effects of different types of dietary fiber preparations isolated from bamboo shoots, edible burdock, apple and corn on fecal steroid profiles of rats.”
Shimizu, J : Yamada, N : Nakamura, K : Takita, T : Innami, S
J-Nutr-Sci-Vitaminol-(Tokyo). 1996 Dec; 42(6): 527-39
This study was conducted to evaluate the effects of different types of dietary fibers (DF) under the conditions with or without cholesterol (Chol) loading on the amount and composition of steroids in rat feces. Rats were fed Chol-unsupplied diets containing 10% lard and 5% DF preparation isolated from four kinds of food, bamboo shoots, edible burdock, apple and corn, for three weeks. The respective diets were supplemented with 0.5% Chol and then given to the rats for a further two weeks. The excretion of total bile acid (BA) and several major BAs increased significantly in the apple group with or without Chol loading when compared with that in the cellulose (CP) or other DF groups. The tendency in the apple group was more noticeable when the diet was supplemented with Chol. This is presumably a major reason for the tendency of decrease in serum and liver Chol concentrations in the apple group. The ratio of secondary BAs to total BA in the feces was significantly low in the apple group. Although the lithocholic acid (LCA)/deoxycholic acid (DCA) ratio, a risk index for colorectal cancer, was significantly lower in the bamboo, burdock and apple groups than in the CP or corn groups when given the diet without Chol, the differences disappeared with the addition of Chol. The proportion of coprostanol, a secondary metabolite of Chol, was smaller in the former three groups than in the CP or corn groups. These results suggest that the intake of some DF by host animals works beneficially for the microbial conversion of BA and Chol in the large intestine but that the addition of Chol acts to cancel such beneficial effects.

Licorice:

“Glycyrrhizin, an active component of licorice roots, reduces morbidity and mortality of mice infected with lethal doses of influenza virus.”
Utsunomiya, T : Kobayashi, M : Pollard, R B : Suzuki, F
Antimicrob-Agents-Chemother. 1997 Mar; 41(3): 551-6
The antiviral effect of glycyrrhizin (GR), an active component of licorice roots, was investigated in mice infected with influenza virus A2 (H2N2). When mice that had been exposed to 10 50% lethal doses of the virus were treated intraperitoneally with 10 mg of GR per kg of body weight 1 day before infection and 1 and 4 days postinfection, all of the mice survived over the 21-day experimental period. At the end of this period, the mean survival time (in days) for control mice treated with saline was 10.5 days, and there were no survivors. The grade of pulmonary consolidations and the virus titers in the lung tissues of infected mice treated with GR were significantly lower than those in the lung tissues of infected mice treated with saline. GR did not show any effects on the viability or replication of influenza virus A2 in vitro. When splenic T cells from GR-treated mice were adoptively transferred to mice exposed to influenza virus, 100% of the recipients survived, compared to 0% survival for recipient mice inoculated with naive T cells or splenic B cells and macrophages from GR-treated mice. In addition, the antiviral activities of GR on influenza virus infection in mice were not demonstrated when it was administered to infected mice in combination with anti-gamma interferon (anti-IFN-gamma) monoclonal antibody. These results suggest that GR may protect mice exposed to a lethal amount of influenza virus through the stimulation of IFN-gamma production by T cells, because T cells have been shown to be producer cells of IFN-gamma stimulated with the compound.

”Licorice extract and its major polyphenol glabridin protect low-density lipoprotein against lipid peroxidation: in vitro and ex vivo studies in humans and in atherosclerotic apolipoprotein E-deficient mice.”
Fuhrman, B : Buch, S : Vaya, J : Belinky, P A : Coleman, R : Hayek, T : Aviram, M
Am-J-Clin-Nutr. 1997 Aug; 66(2): 267-75
Polyphenolic flavonoids are powerful antioxidants. In the present study we investigated the antioxidative activity against low-density-lipoprotein (LDL) oxidation of a not yet studied subclass of polyphenols, the isoflavans, which are present in licorice alcoholic extract. The study was performed in humans as well as in atherosclerotic apolipoprotein E-deficient mice (E zero), because their LDL is highly susceptible to oxidation. LDL oxidation was induced by incubating it with copper ions as well as with the aqueous or lipid-soluble free radical generators 2,2'-azobis'2-amidino propane hydrochloride (AAPH) and 2,2'-azobis 2,4-dimethylvaleronitrile (AMVN), respectively. The extent of LDL oxidation was determined by measuring the formation of conjugated dienes, thiobarbituric acid reactive-substances (TBARS), and lipid peroxides. By all methods in human studies, licorice ethanolic extract as well as a pure material, which was identified by gas chromatography-mass spectroscopy as the isoflavan glabridin, were shown to inhibit LDL oxidation by a mechanism involving scavenging of free radicals. In an ex vivo study, LDL isolated from the plasma of 10 normolipidemic subjects who were orally supplemented for 2 wk with 100 mg licorice/d was more resistant to oxidation than was LDL isolated before licorice supplementation. Dietary supplementation of each E zero mouse with licorice (200 micrograms/d) or pure glabridin (20 micrograms/d) for 6 wk resulted in a substantial reduction in the susceptibility of their LDL to oxidation along with a reduction in the atherosclerotic lesion area. These results could be related to the absorption and binding of glabridin to the LDL particle and subsequent protection of the LDL from oxidation by multiple modes as shown in humans and in E zero mice.

“Antioxidant constituents from licorice roots: isolation, structure elucidation and antioxidative capacity toward LDL oxidation.”
Vaya, J : Belinky, P A : Aviram, M
Free-Radic-Biol-Med. 1997; 23(2): 302-13
The present study analyzed the antioxidative properties of natural compounds from the root of the plant Glycyrrhiza glabra (licorice) toward LDL oxidation. Seven constituents, with antioxidant capacity were isolated from Glycyrrhiza glabra. The isolated compounds were identified as the isoflavans Hispaglabridin A (1), Hispaglabridin B (4), Glabridin (3), and 4'-O-Methylglabridin (2), the two chalcones, isoprenylchalcone derivative (5) and Isoliquiritigenin (6), and the isoflavone, Formononetin (7). Among these compounds, Glabridin constituted the major amount in the crude extract (11.6%, w/w) as detected by high-performance liquid chromatography (HPLC) analysis. The antioxidative capacities of the isolated compounds (1-7) were tested against beta-carotene destruction and LDL oxidation. The isoflavans (1-4) at a concentration of 50 microM inhibited beta-carotene consumption, following 90 min of incubation at 50 degrees C, similar to the inhibitory effect of the whole licorice crude extract (at 16 mg/1). The chalcones (5 and 6) exhibited moderate inhibition and the isoflavone 7 was almost inactive, whereas vitamin E (50 microM) completely inhibited beta-carotene consumption. The inhibitory effect of the constituents 1-7, at a concentration of 30 microM on 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced LDL oxidation was determined by measuring the amount of the thiobarbituric acid reactive substances (TBARS) and the amount of lipid peroxides. While compounds 1-6 exhibited high inhibitory activity, compound 7 and vitamin E were not active. A dose-dependent inhibitory effect of Glabridin, on the formation of cholesteryl linoleate hydroperoxide (CLOOH), in an AAPH-induced LDL oxidation system was also shown. Glabridin, at 5 or 40-60 microM concentration, inhibited the CLOOH formation by 62% and 90%, respectively. These results suggest that constituents 1-6 are very potent antioxidants toward LDL oxidation with Glabridin being the most abundant and potent antioxidant. As LDL oxidation is a key event in the formation of the early atherosclerotic lesion, the use of these natural antioxidants may be proven beneficial to attenuate atherosclerosis.


“Modulations of the Bcl-2/Bax family were involved in the chemopreventive effects of licorice root (Glycyrrhiza uralensis Fisch) in MCF-7 human breast cancer cell.”
Jo,-E.H.; Hong,-H.D.; Ahn,-N.C.; Jung,-J.W.; Yang,-S.R.; Park,-J.S.; Kim,-S.H.; Lee,-Y.S.; Kang,-K.S.
Journal of agricultural and food chemistry. 2004 Mar. 24, v. 52, no. 6 p. 1715-1719.
Recently, cancer chemoprevention with strategies using foods and medicinal herbs has been regarded as one of the most visible fields for cancer control. Genistein in soy, American ginseng, and resveratrol are well-known to have antiproliferative properties in human breast cancer. Licorice root is a botanical, a shrub native to southern Europe and Asia, which primarily has desirable qualities in sweetening and herbal medicine. In this study, licorice (Glycyrrhiza uralensis Fisch) root also inhibits cell proliferation in human breast cancer cell. The cell proliferation study demonstrated that licorice root reduced the proliferation of MCF-7 cells in a dose- and time-dependent manner. The extracts were fractionated in CHCl3, EtOAc, C6H14, and CH3OH-H2O (70:30), and these extracts of licorice root (50 microgram/mL) induced DNA fragmentation demonstrated by Hoechst 33258 staining. Apoptosis also determined the sub-G1 accumulation by flow cytometry analysis. These results were consistent with specific cleavage of P ARP and antiapoptotic protein Bcl-2 and up-regulation of proapoptotic protein Bax demonstrated by Western blotting. Our findings suggest that licorice root may have chemopreventive effects against human breast cancer through the modulation of the expression of the Bcl-2/Bax family of apoptotic regulatory factors.

“Estrogenic and antiproliferative properties of glabridin from licorice in human breast cancer cells.”
Tamir, S : Eizenberg, M : Somjen, D : Stern, N : Shel : ach, R : Kaye, A : Vaya, J
Cancer-Res. 2000 Oct 15; 60(20): 5704-9
There is an increasing demand for natural compounds that improve women's health by mimicking the critical benefits of estrogen to the bones and the cardiovascular system but avoiding its deleterious effects on the breast and uterus. The estrogenic properties of glabridin, the major isoflavan in licorice root, were tested in view of the resemblance of its structure and lipophilicity to those of estradiol. The results indicate that glabridin is a phytoestrogen, binding to the human estrogen receptor and stimulating creatine kinase activity in rat uterus, epiphyseal cartilage, diaphyseal bone, aorta, and left ventricle of the heart. The stimulatory effects of 2.5-25 microg/animal glabridin were similar to those of 5 microg/animal estradiol. Chemical modification of glabridin showed that the position of the hydroxyl groups has a significant role in binding to the human estrogen receptor and in proliferation-inducing activity. Glabridin was found to be three to four times more active than 2'-O-methylglabridin and 4'-O-methylglabridin, and both derivatives were more active than 2',4'-O-methylglabridin. The effect of increasing concentrations of glabridin on the growth of breast tumor cells was biphasic. Glabridin showed an estrogen receptor-dependent, growth-promoting effect at low concentrations (10 nM-10 microM) and estrogen receptor-independent antiproliferative activity at concentrations of greater than 15 microM. This is the first study to indicate that isoflavans have estrogen-like activities. Glabridin and its derivatives exhibited varying degrees of estrogen receptor agonism in different tests and demonstrated growth-inhibitory actions on breast cancer cells.



ASTRAGALUS:

“Effects of several Chinese herbal aqueous extracts on human sperm motility in vitro.”
Liu J, Liang P, Yin C, Wang T, Li H, Li Y, Ye Z.  Department of Urology, Tongji Hospital, Wuhan, China. jhliu@tjh.tjmu.edu.cn

The effects of six kinds of aqueous extracts of Chinese herbal medicine (Astragalus membranaceus, Acanthopanacis senticosi, Panax genseng and Ophiopogon japonicus, P. genseng and Aconitum carmichaeli, Salviae miltiorrhiae, Polyporus umbellatus polysaccharide) on sperm motility characteristics of 30 infertile male volunteers were studied in vitro with a computer-assisted sperm analysis at 15, 60 and 180 min after incubated with the drugs. The results showed that per cent viability, number of progressive motile spermatozoa, curvilinear velocity, average path velocity and amplitude of lateral head displacement were significantly enhanced by A. membranaceus (P < 0.05 or < 0.01), per cent viability, average path velocity and amplitude of lateral head displacement were significantly enhanced by A. senticosi (P < 0.05), but all the above were not affected by P. genseng and O. japonicus, P. genseng and A. carmichaeli, S. miltiorrhiae and P. umbellatus polysaccharide. It is suggested that A. membranaceus and A. senticosi can enhance the motility of human spermatozoa in vitro.

“Clinical and experimental study of treatment of nanmiqing capsule for chronic prostatitis”
Dai CF, Zhang ZZ, Qi XL, Zhang MX, Li YP.  Fujian College of Traditional Chinese Medicine, Fuzhou, Fujian 350003, China.

OBJECTIVES: To investigate the clinical effect and therapeutic mechanism of Nanmiqing capsule made of rheum palmatum, leech, astragalus memberanaceus on patients with chronic prostatitis(CP). METHODS: Seventy-six CP cases were treated with Nanmiqing, while 32 CP cases were treated with Qianliekang as a control. The changes of EPS were observed pre- and post-treatment. The rat model of CP got by Xiaozhiling inducing were treated with Nanmiqing and Qianliekang respectively. The concentration of endothelin, TXB2, 6-keto-PGF1 alpha and SOD, IgG, IgA in plasma were measured pre- and post-treatment, meanwhile, pathological changes of prostate tissues were observed. RESULTS: The total effective rate was 89.47% in treatment group, which was significantly higher than 71.88% in the control group (P < 0.01). Experimental study for CP rats showed that the Nanmiqing was more effective medicine than Qianliekang (P < 0.01). CONCLUSIONS: Nanmiqing was an effective medicine for CP. The mechanism of clearing heat and resolving toxin, activating blood and removing stasis and reinforcing Qi in chinese medicine could be the explanation of the useful treatment including three therapentic ways.

“Clinical and experimental study of the effect of kang er xin-I on viral myocarditis”
Yan HJ. Yunnan College of TCM, Kunming.

Kang Er Xin-I (KEX-I) is a proved recipe used to treat viral myocarditis. It consists of Lonicera japonica, Ophiopogon japonicus, Astragalus membranaceus mainly and possesses the effect of clearing away heat and toxic materials and supplementing the vital energy and nourishing. The clinical study was carried out with KEX-I according to a random, paired and cross-over design. Coenzyme Q10 was used as a control and left ventricular function was observed. The result showed: after being treated with KEX-I for two weeks, the 26 patients' chief cardiac functional indexes assessed with STI improved markedly, the value of PEP/LVET and ICT/LVCT all decreased and the difference between the two groups was significant. The experimental study showed that KEX-I can inactivate directly the virus of Coxsackie B3, protect the heart cells in mice, prevent attack by Coxsackie B3, promote the growth of internal interferon and increase the NK cell's function to regulate immunity in experimental mice.

 

Lomatium Dissectum:

Dr. Krebs Uses Lomatium for Influenza Epidemic

The following is verbatim from: Bulletin of the Nevada State Board of Health , No. 1 , Carson City, Nevada , January, 1920

AN INDIAN REMEDY FOR INFLUENZA

In publishing this paper the State Board of Health does not give its endorsement to the remedy until it has had further trial. We merely present the facts as stated by Dr. Krebs, with the idea of giving the matter publicity and encouraging others to give it a trial.

During the fall of 1918 when the influenza epidemic visited this section of Nevada, the Washoe Indian used a root in the treatment of their sick which was gathered along the foot-hills of this slope of the Sierra. The plant proved to be a rare species of the parsley family (Leptotaemia dissecta*), according to a report from the University of California.

The Indians gather this root in the late fall, November being considered the proper month for gathering. The root is used in the fresh or dry state. It is cut up and a decoction is made by boiling the root in water, skimming off the top and giving large doses of the broth. A pound of root is considered about the proper dose to treat a case of fever for three days, which is the longest time needed to break up a fever due to influenza or a pulmonary disease, although the Washoes used it as a panacea. Whether a coincidence or not, there was not a single death in the Washoe tribe from influenza or its complications, although Indians living in other parts of the State where the root did not grow died in numbers.

It was such a remarkable coincidence that the root was investigated by a practicing physician who saw apparently hopeless cases recover without any other medication or care of any kind. A preparation was prepared and employed in a great many cases among the whites, from the mildest to the most virulent types of influenza, and it proved, among other things, that it is the nearest approach we have today to a specific in epidemic influenza and the accompanying pneumonia.

Where used early it proved itself to be a reliable agent in preventing pulmonary complications. Other physicians were induced to give it a trial, with the same results. It is beyond the experimental stage, as its therapeutic action in this direction is established and beyond any doubt. The cases in which it has been used run into the hundreds. There is probably no therapeutic agent so valuable in the treatment of influenzal pneumonia and, as far as being tried, in ordinary lobar pneumonia if started early. Its action on coughs is more certain than the opiate expectorants and its benefit is lasting. It acts as a powerful tonic to the respiratory mucous membranes. It is a bronchial, intestinal and urinary antiseptic and is excreted by these organs. It seems to stimulate the pneogastries (sic) and causes a slow pulse with increased volume and reduced tension. It is a pronounced diaphoretic and somewhat diuretic, and it is a stimulating and sedative expectorant. In large doses it is a laxative, and in extreme doses emetic.

To make a therapeutically active preparation, the proper variety of the root must be selected in the late fall and properly cured out of the sun. Its active principles must be extracted with as little as possible of the objectionable constituents. The active principles of the root are decidedly complex. It contains a glucoside (as its solutions precipitate copper from Fehling's solution). It contains one or more alkaloids and an acid analogous to benzoic acid, one or more volatile and fixed oils, a resin and a gum. It can be seen from this that it resembles a balsam from the fact that it contains an oleogumresin and an acid besides alkaloids and glucosides. One can at once appreciate the fact that a reliable pharmaceutical preparation representing the action of the root is not readily made. The volatile oil, which is one of the principal therapeutic agents, is lost in making a decoction.

This particular variety of Leptotaemia* is not as common as believed as some, and it is this particular variety that has medicinal or therapeutic virtues. It grows in dry sandy soil, as a rule, under or between tall sagebrush or greasewood. The plant grows from two to four feet high and has a blossom similar to wild parsnip and leaves like a carrot. It is a perennial, and the older roots frequently weigh from two to six pounds. It sprouts early in April, blooms in May, seeds in June, and withers in July. A number of trials in transplanting the root have been made, but none were successful.

Leptotaemia dissecta * is destined to become one of the most useful if not the most important addition to our vegetable materia medica.

ERNST T. KREBS, M.D. Carson City, Nevada.
* The botanical name was changed in 1942 by Matthias and Constance, from Leptotaenia dissecta to Lomatium dissectum.
Source: http://www.lomatium.com/

“Antibacterial activity of components from Lomatium californicum.”
Chou,-S-C; Everngam,-M-C; Sturtz,-G; Beck,-J-J
Phytother-Res. 2006 Feb; 20(2): 153-6
The isolation, characterization and bioactivity testing of compounds from Lomatium californicum (Nutt.) are described. Ethyl acetate and hexane extracts of the roots of L. californicum were subjected to vacuum liquid chromatography (VLC), flash column chromatography (FCC) and separation by normal- and reverse-phase high-performance liquid chromatography (HPLC). Six compounds were isolated successfully and characterized by 1D and 2D nuclear magnetic resonance (NMR) experimentation. The bioactivity of the known compounds (+)-falcarindiol, coniferyl ferulate, ferulic acid and (Z)-ligustilide were confirmed against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. The known compounds senkyunolide I and trans-neocnidilide were also isolated but in too small a quantity for similar testing. Copyright 2006 John Wiley & Sons, Ltd.

“Phytotoxic and antifungal compounds from two Apiaceae species, Lomatium californicum and Ligusticum hultenii, rich sources of Z-ligustilide and apiol, respectively.”
Meepagala,-K-M; Sturtz,-G; Wedge,-D-E; Schrader,-K-K; Duke,-S-O
J-Chem-Ecol. 2005 Jul; 31(7): 1567-78       
The seeds of two Apiaceae species, Ligusticum hultenii and Lomatium californicum, were investigated. Preliminary bioassays indicated that methylene chloride extracts of seeds of both species contained selective phytotoxic activity against monocots and antifungal activity against Colletotrichum fragariae. Active constituents were isolated by bioassay-guided fractionation, and the structures were elucidated by NMR and GC-MS as apiol and Z-ligustilide, isolated from L. hultenii and L. californicum, respectively. Apiol and Z-ligustilide had I50 values of about 80 and 600 microM, respectively, for inhibition of the growth of Lemna paucicostata. The methylene chloride (CH2Cl2) extracts of the seeds and the isolated and purified compounds were tested against the 2-methylisobomeol-producing cyanobacterium (blue-green alga) Oscillatoria perornata, and the green alga Selenastrum capricornutum. The CH2Cl2 extracts of both Apiaceae species and apiol were weakly toxic to both species of phytoplankton, while Z-ligustilide was toxic to both with a lowest complete inhibitory concentration (LCIC) of 53 microM. Seeds of L. californicum and L. hultenii were found to be rich sources of Z-ligustilide (97 mg/g of dry seed) and apiol (40 mg/g of dry seed), respectively.

“Antiviral screening of British Columbian medicinal plants.”
McCutcheon, A R : Roberts, T E : Gibbons, E : Ellis, S M : Babiuk, L A : Hancock, R E : Towers, G H
J-Ethnopharmacol. 1995 Dec 1; 49(2): 101-10
One hundred methanolic plant extracts were screened for antiviral activity against seven viruses. Twelve extracts were found to have antiviral activity at the non-cytotoxic concentrations tested. The extracts of Rosa nutkana and Amelanchier alnifolia, both members of the Rosaceae, were very active against an enteric coronavirus. A root extract of another member of the Rosaceae, Potentilla arguta, completely inhibited respiratory syncytial virus. A Sambucus racemosa branch tip extract was also very active against respiratory syncytial virus while the inner bark extract of Oplopanax horridus partially inhibited this virus. An extract of Ipomopsis aggregata demonstrated very good activity against parainfluenza virus type 3. A Lomatium dissectum root extract completely inhibited the cytopathic effects of rotavirus. In addition to these, extracts prepared from the following plants exhibited antiviral activity against herpesvirus type 1: Cardamine angulata, Conocephalum conicum, Lysichiton americanum, Polypodium glycyrrhiza and Verbascum thapsus.



N-ACETYL-L-CYSTEINE:

The University of Maryland Medical Center:

Overview
Cysteine is an amino acid that can be found in many proteins throughout the body. N-acetyl-L-cysteine (NAC), a modified form of cysteine, helps break down mucus and detoxify harmful substances in the body. Both cysteine and NAC have been shown to increase levels of the antioxidant glutathione.

Antioxidants are substances that scavenge free radicals, damaging compounds in the body that alter cell membranes, tamper with DNA, and even cause cell death. Free radicals occur naturally in the body, but environmental toxins (including ultraviolet light, radiation, cigarette smoking, and air pollution) can also increase the number of these damaging particles.

Free radicals are believed to contribute to the aging process as well as the development of a number of health problems including heart disease and cancer. Antioxidants such as glutathione can neutralize free radicals and may reduce or even help prevent some of the damage they cause.

Uses
NAC offers a variety of potential therapeutic uses, particularly in the prevention or in the treatment of the following conditions:

Acetaminophen Poisoning
Healthcare practitioners commonly administer oral or intravenous NAC to prevent or reduce liver and kidney damage associated with overdoses of acetaminophen (also called paracetamol), an over the counter medication commonly used for pain or headache. Acetaminophen poisoning can occur at lower doses of the drug if someone drinks alcohol on a regular basis.

Heart Disease
In studies of people having a heart attack or those with ongoing chest pain, NAC, in combination with nitroglycerin (a drug that opens up blood vessels and improves blood flow), has been more effective than either NAC or nitroglycerin alone in reducing subsequent chest pain, heart attack, and the risk of death. However, individuals who receive both NAC and nitroglycerin may experience a severe headache. These results are promising, but further studies are needed to confirm the safety and effectiveness of NAC for heart disease.

Respiratory Illness
A review of scientific studies also found that NAC may help dissolve mucus and improve symptoms associated with chronic bronchitis, asthma, cystic fibrosis and emphysema. Chronic smokers also may benefit from NAC supplementation. Studies on large groups of people have found that NAC appears to have cancer prevention properties in people who are at risk for lung cancer.

Free radical damage is believed to contribute to the development and progression of acute respiratory distress syndrome (ARDS), a condition characterized by the rapid and progressive malfunction of the lungs. Although not all studies agree, some research of animals and people suggest that intravenous NAC may boost levels of glutathione and subsequently prevent and/or treat lung damage caused by ARDS. However, results of other studies have been conflicting. Further investigation is needed.

HIV/AIDS
HIV infection is considered to be a condition of excessive oxidative stress (caused by free radicals) where the antioxidant glutathione is depleted significantly. Therefore, it is believed that supplementation with cysteine may help strengthen the immune system in those with HIV and diminish the bodily damage associated with this infection.

In one well-designed study of people with HIV, those who took a daily supplement regimen including the amino acid glutamine (40 gram per day), vitamin C (800 mg), vitamin E (500 IU), beta-carotene (27,000 IU), selenium (280 mcg), and N-acetylcysteine (2400 mg) gained significantly more weight after 12 weeks than those who took placebo. Similarly, in a smaller-scale study using NAC in HIV positive patients, the supplement did increase glutathione levels while a placebo did not.

These studies and others support the theory that NAC may prove to be a useful addition to conventional medical care for those with HIV. Other studies, however, have shown negative results using NAC for those with HIV. Therefore, more research is needed before conclusions can be drawn about NAC supplements for this infection.

Other:
Low levels of cysteine may be linked to an increased risk of cervical dysplasia (changes to the opening of the uterus, that are precancerous or cancerous). Preliminary evidence also suggests that NAC supplements may:

---Improve symptoms associated with Sjogren's syndrome (an autoimmune disorder characterized by dry mouth and dry eyes)

---Enhance cognitive functioning in some individuals with Alzheimer's disease

---Prevent development of cataracts and macular degneration

---Slow down motor impairment in amyotrophic lateral sclerosis (ALS, often called Lou Gehrig's disease which is a progressive loss of control of voluntary muscles due to destruction of nerve cells in the brain and spinal cord)

---Help treat hepatitis C when combined with standard medical treatment

---Increase HDL cholesterol (the good kind of cholesterol).

---Further studies are needed to confirm these early findings.

Dietary Sources
The body synthesizes cysteine from the essential amino acid methionine. Cysteine is also found in most high-protein foods including ricotta, cottage cheese, yogurt, pork, sausage meat, chicken, turkey, duck, luncheon meat, wheat germ, granola, and oat flakes.

Available Forms
•             NAC aerosol spray (prescription)
•             NAC liquid solution (prescription)
•             NAC topical solution
•             L-cysteine powder
•             Cysteine/NAC tablets or capsules

How to Take It
NAC is administered either intravenously or orally in the hospital to treat acetaminophen (paracetamol) poisoning in both children and adults. Acetaminophen poisoning is a medical emergency and treatment must be started within eight hours of an overdose.

Pediatric
There is no specific pediatric recommendation for cysteine. If laboratory tests reveal that the child has an amino acid imbalance that requires treatment, a healthcare provider may recommend a complete amino acid supplement that contains cysteine.

Adult
Recommended adult doses of NAC vary depending on the health condition being treated. The following list provides guidelines for the most common uses.

Respiratory illness: 200 mg two times per day for chronic bronchitis. ARDS is a medical emergency and is treated in the intensive care unit in the hospital with intravenous NAC as part of a comprehensive treatment regimen.

Antioxidant protection/general health: 500 mg per day to start. Dosage may be increased, with expert guidance. Someone with HIV/AIDS may be put on a dose as high as 4,000 mg per day. Adding a multivitamin will ensure that you are getting the B vitamins you need when taking NAC.

Precautions
Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable healthcare provider.

Some forms of cysteine are toxic and should be avoided. These include D-cysteine, D-cystine, and 5-methyl cysteine.

NAC may raise levels of homocysteine, an amino acid believed to play a role in the development of heart disease. Be sure to have your health care provider check your homocysteine level if you are taking NAC.

Extremely high doses (more than 7 grams) of cysteine should be avoided because it may be toxic to human cells and may even lead to death.

Oral NAC may cause nausea, vomiting, and diarrhea.

Intravenous administration of NAC (to treat, for example, acetaminophen poisoning) may cause severe allergic reactions, even angioedema (significant swelling of the soft tissue just beneath the skin including the face, lips, and around the eyes) or anaphylaxis (a life-threatening allergy that leads to inability to breath). Plus, there has been one case report of seizures from intravenous administration of NAC to a young girl for paracetamol intoxication.

Cysteine supplements should not be taken by individuals with cystinuria, a kidney condition in which excessive amounts of cysteine (along with three other amino acids) are lost in the urine.

Possible Interactions
If you are currently being treated with any of the following medications, you should not use cysteine supplements without first talking to your healthcare provider.

Blood Pressure Medications, Angiotensin-converting Enzyme (ACE) Inhibitors
NAC may enhance the blood pressure-lowering effects of ACE inhibitors, medications commonly used to treat high blood pressure. Examples of ACE inhibitors include benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, quenipril, ramepril, and trandolapril.

Immunosuppressive Medications
Treatment with NAC may enhance the effectiveness of immunosuppressive medications such as azathioprine, cyclophosphamide, prednisolone, or prednisone. More research in this area is needed.

Cisplatin and Doxorubicin
Laboratory and animal studies have suggested that NAC may reduce the toxic effects associated with both cisplatin and doxorubicin, medications used to treat a variety of cancers. However, scientific studies are needed to see if these effects apply to people.

Nitroglycerin and Isosorbide
Although NAC may enhance the effectiveness of nitroglycerin and isosorbide (two medications commonly used to treat chest pain), this combination may also increase the risk of side effects such as severe headaches and may lead to abnormally low blood pressure.

Oxiconazole
Topical applications of NAC may increase the effectiveness of oxiconazole, an antifungal medication used for athlete's foot.

Supporting Research
Adair JC, Knoefel JE, Morgan N. Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease. Neurology . 2001;57(8):1515-1517.
Ames BN. Micronutrient deficiencies: A major cause of DNA damage. Ann NY Acad Sci . 2000;889:87-106.
Andreassen OA, Dedeoglu A, Klivenyi P, Beal MF, Bush AI. N-acetyl-L-cysteine improves survival and preserves motor performance in an animal model of familial amylotrophic lateral sclerosis. Neuroreport . 2000;11(11):2491-2493.
Ardissino D, Merlini PA, Savonitto S, Demicheli G, et al. Effect of transdermal nitroglycerin or N-Acetylcysteine, or both, in the long-term treatment of unstable angina pectoris. J Am Coll Cardiol . 1997;29(5):941-947.
Arstall MA, Yang J, Stafford I, Betts WH, Horowitz JD. N-acetylcysteine in combination with nitroglycerin and streptokinase for treatment of evolving acute myocardial infarction: safety and biochemical effects. Circulation . 1995;92:2855-2862.
Behr J, Maier K, Degenkolb B, Krombach F, Vogelmeier C. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Am J Respir Crit Care Med . 1997;156:1897-1901.
Beloqui O, Prieto J, Suarez M, et al. N-acetyl cysteine enhances the response to interferon-alpha in chronic hepatitis C: a pilot study. J Interferon Res . 1993;13:279-282.
Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP. Oxidative damage and protection of the RPE. Prog Retin Eye Res . 2000;19(2):205-221.
Carter EA. Enhanced acetaminophen toxicity associated with prior alcohol consumption in mice; prevention by N-acetylcysteine. Alcohol . Jan-Feb 1987; 4(1): 69-71.
Chevez-Barrios P, Wiseman AL, Rojas E, Ou CN, Lieberman MW. Cataract develoment in gamma-glutamyl transpeptidase deficient mice. Exp Eye Res . 2000;71(6):575-582.
Chirkov YY, Horowitz JD. N-Acetylcysteine potentiates nitroglycerin-induced reversal of platelet aggregation. J Cardiovasc Pharmacol . 1996;28(3):375-380.
Christman BW, Bernard GR. Antilipid mediator and antioxidant therapy in adult respiratory distress syndrome. New Horiz . Nov 1993; 1(4): 623-630.
D'Agostini F, Bagnasco M, Giunciuglio D, Albini A, De Flora S. Inhibition by oral N-acetylcysteine of doxorubicin-induced clastogenicity and alopecia, and prevention of primary tumors and lung micrometastases in mice. Int J Oncol . 1998;13:217-224.
Davreux CJ, Soric I, Nathens AB, et al. N-acetylcysteine attenuates acute lung injury in the rat. Shock . Dec 1997; 8(6): 432-438.
De Flora S, D'Agostini F, Masiello L, Giunciuglio D, Albini A. Synergism between N-Acetylcysteine and doxorubicin in the prevention of tumorigenicity and metastasis in murine models. Int J Cancer. 1996;67:842-848.
De Rosa SC, Zaretsky MD, Dubs JG, Roederer M, Anderson M, Green A, et al. N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest . 2000;30:915-929.
Domenighetti G, Quattropani C, Schaller MD. Therapeutic use of N-acetylcysteine in acute lung diseases. [Review, French]. Rev Mal Respir . 1999;16(1):29-37.
Domenighetti G, Suter PM, Schaller MD, Ritz R, Perret C. Treatment with N-acetylcysteine during acute respiratory distress syndrome: a randomized, double-blind, placebo-controlled clinical study. J Crit Care . 1997;12(4):177-182.
Doroshow JH, Locker GY, Ifrim I, Myers CE. Prevention of doxorubicin cardiac toxicity in the mouse by N-Acetylcysteine. J Clin Invest . 1981;68:1053-1064.
Droge W. Cysteine and glutathione deficiency in AIDS patients: a rationale for the treatment with N-acetyl-cysteine. [Review]. Pharmacology . 1993;46(2):61-65.
Franceschini G, et al. Dose-related increase in HDL-cholesterol levels after N-acetylcysteine in man. Pharmacol Res . Oct-Nov 1993; 28(3): 213-218.
Goodman MT, McDuffie K, Hernandez B, Wilkens LR, Selhub J. Case-control study of plasma folate, homocysteine, vitamin B12, and cysteine as markers of cervical dysplasia. Cancer . 2000;89:376-382.
Hershkovitz E, Shorer Z, Levitas A, Tal A. Status epilepticus following intravenous N-acetylcysteine therapy. Isr J Med Sci . 1996;32(11):1102-1104.
Iversen HK. N-acetylcysteine enhances nitroglycerin-induced headache and cranial artery response. Clin Pharmacol Ther . 1992;52:125-133.
Jackson IM, et al. Efficacy and tolerability of oral acetylcysteine (Fabrol) in chronic bronchitis: a double-blind placebo controlled study. J Int Med Res. 1984; 12(3): 198-206.
Kozer E, Koren G. Management of paracetamol overdose: current controversies. [Review]. Drug Saf . 2001;24(7):503-512.
Lenz AG, Jorens PG, Meyer B, et al. Oxidatively modified proteins in bronchoalveolar lavage fluid of patients with ARDS and patients at-risk for ARDS. Eur Respir J. 1999;13(1):169-174.
Marchetti G, Lodola E, Licciardello L, Colombo A. Use of N-acetylcysteine in the management of coronary artery diseases. Cardiologia . Jul 1999; 44(7): 633-637.
Micke P, Beeh KM, Schlaak JF, Buhl R. Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients. Eur J Clin Invest . 2001;31(2):171-178..
Muller F, Svardal AM, Nordoy I, Berge RK, Aukrust P, Froland SS. Virological and immunological effects of antioxidant treatment in patients with HIV infection. Eur J Clin Invest . 2000;30(10):905-914.
Patrick L. Hepatitis C: epidemiology and review of complementary/alternative medicine treatments. Alt Med Rev . 1999;4(4):220-238.
Pelle E, et al. Protection against cigarette smoke-induced damage to intact transformed rabbit corneal cells by N-acetyl-L-cysteine. Cell Biol Toxicol . Aug 1998; 14(4): 253-259.
Perry HE, Shannon MW. Efficacy of oral versus intravenous N-acetylcysteine in acetaminophen ovedose:results of an open-label, clinical trial. J Pediatr . Jan 1998;132(1): 149-152.
Pizzorno JE, Murray MT. Textbook of Natural Medicine . Vol 1. 2nd ed. Edinburgh: Churchill Livingstone; 1999:296-297.
Pizzulli, L, Hagendorff A, Zirbes M, Jung W, Lüderitz B. N-Acetylcysteine attenuates nitroglycerin tolerance in patients with angina pectoris and normal left ventricular function. Am J Cardiol . 1997;79:28-33.
Ruiz FJ, et al. N-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs. Am J Physiol . Sep 1994; 267 (3 Pt 2): R767-772.
Shabert JK, Winslow C, Lacey JM, Wilmore DW. Glutamine antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial. Nutrition . 1999;11:860-864.
Shils, ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease . 9th ed. Baltimore, MD: Williams & Wilkins; 1999:543-556.
Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med . Dec 15 1988; 319(24): 1557-1562.
Stavem K. Anaphylactic reaction to N-acetylcysteine after poisoning with paracetamol. Tidsskr Nor Laegeforen. May 30 1997; 117(14): 2038-2039.
Stey C, Steurer J, Bachmann S, Medici TC, Tramer MR. The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur Respir J . 2000 Aug;16(2):253-262.
Suárez C, Del Arco C, Lahera V, Ruilope LM. N-Acetylcysteine potentiates the antihypertensive effect of angiotensin converting enzyme inhibitors [letter]. Am J Hypertens . 1995;8:859-861.
van Hoogdalem EJ, van den Hoven WE, Terpstra IJ, van Zijtveld J, Verschoor, JSC. Nail penetration of the antifungal agent oxiconazole after repeated topical application in healthy volunteers, and the effect of acetylcysteine. Eur J Pharm Sci . 1997;5:119-127.
van Zandwijk N. N-acetylcysteine for lung cancer prevention. Chest . 1995;107(5):1437-1441.
Walters MT, et al. A double-blind, cross-over, study of oral N-acetylcysteine in Sjogren's syndrome. Scand J Rheumatol Suppl . 1986; 61: 253-258.

 

Review Date: 4/1/2002

Reviewed By: Participants in the review process include: Jacqueline A. Hart, MD, Department of Internal Medicine, Newton-Wellesley Hospital, Harvard University and Senior Medical Editor Integrative Medicine, Boston, MA; Gary Kracoff, RPh (Pediatric Dosing section February 2001), Johnson Drugs, Natick, Ma; Steven Ottariono, RPh (Pediatric Dosing section February 2001), Veteran's Administrative Hospital, Londonderry, NH; Margie Ullmann-Weil, MS, RD, specializing in combination of complementary and traditional nutritional therapy, Boston, MA. All interaction sections have also been reviewed by a team of experts including Joseph Lamb, MD (July 2000), The Integrative Medicine Works, Alexandria, VA;Enrico Liva, ND, RPh (August 2000), Vital Nutrients, Middletown, CT; Brian T Sanderoff, PD, BS in Pharmacy (March 2000), Clinical Assistant Professor, University of Maryland School of Pharmacy; President, Your Prescription for Health, Owings Mills, MD; Ira Zunin, MD, MPH, MBA (July 2000), President and Chairman, Hawaii State Consortium for Integrative Medicine, Honolulu, HI.

N-ACETYL-L-CYSTEINE:

The University of Maryland Medical Center:

Overview
Cysteine is an amino acid that can be found in many proteins throughout the body. N-acetyl-L-cysteine (NAC), a modified form of cysteine, helps break down mucus and detoxify harmful substances in the body. Both cysteine and NAC have been shown to increase levels of the antioxidant glutathione.

Antioxidants are substances that scavenge free radicals, damaging compounds in the body that alter cell membranes, tamper with DNA, and even cause cell death. Free radicals occur naturally in the body, but environmental toxins (including ultraviolet light, radiation, cigarette smoking, and air pollution) can also increase the number of these damaging particles.

Free radicals are believed to contribute to the aging process as well as the development of a number of health problems including heart disease and cancer. Antioxidants such as glutathione can neutralize free radicals and may reduce or even help prevent some of the damage they cause.

Uses
NAC offers a variety of potential therapeutic uses, particularly in the prevention or in the treatment of the following conditions:

Acetaminophen Poisoning
Healthcare practitioners commonly administer oral or intravenous NAC to prevent or reduce liver and kidney damage associated with overdoses of acetaminophen (also called paracetamol), an over the counter medication commonly used for pain or headache. Acetaminophen poisoning can occur at lower doses of the drug if someone drinks alcohol on a regular basis.

Heart Disease
In studies of people having a heart attack or those with ongoing chest pain, NAC, in combination with nitroglycerin (a drug that opens up blood vessels and improves blood flow), has been more effective than either NAC or nitroglycerin alone in reducing subsequent chest pain, heart attack, and the risk of death. However, individuals who receive both NAC and nitroglycerin may experience a severe headache. These results are promising, but further studies are needed to confirm the safety and effectiveness of NAC for heart disease.

Respiratory Illness
A review of scientific studies also found that NAC may help dissolve mucus and improve symptoms associated with chronic bronchitis, asthma, cystic fibrosis and emphysema. Chronic smokers also may benefit from NAC supplementation. Studies on large groups of people have found that NAC appears to have cancer prevention properties in people who are at risk for lung cancer.

Free radical damage is believed to contribute to the development and progression of acute respiratory distress syndrome (ARDS), a condition characterized by the rapid and progressive malfunction of the lungs. Although not all studies agree, some research of animals and people suggest that intravenous NAC may boost levels of glutathione and subsequently prevent and/or treat lung damage caused by ARDS. However, results of other studies have been conflicting. Further investigation is needed.

HIV/AIDS
HIV infection is considered to be a condition of excessive oxidative stress (caused by free radicals) where the antioxidant glutathione is depleted significantly. Therefore, it is believed that supplementation with cysteine may help strengthen the immune system in those with HIV and diminish the bodily damage associated with this infection.

In one well-designed study of people with HIV, those who took a daily supplement regimen including the amino acid glutamine (40 gram per day), vitamin C (800 mg), vitamin E (500 IU), beta-carotene (27,000 IU), selenium (280 mcg), and N-acetylcysteine (2400 mg) gained significantly more weight after 12 weeks than those who took placebo. Similarly, in a smaller-scale study using NAC in HIV positive patients, the supplement did increase glutathione levels while a placebo did not.

These studies and others support the theory that NAC may prove to be a useful addition to conventional medical care for those with HIV. Other studies, however, have shown negative results using NAC for those with HIV. Therefore, more research is needed before conclusions can be drawn about NAC supplements for this infection.

Other:
Low levels of cysteine may be linked to an increased risk of cervical dysplasia (changes to the opening of the uterus, that are precancerous or cancerous). Preliminary evidence also suggests that NAC supplements may:

---Improve symptoms associated with Sjogren's syndrome (an autoimmune disorder characterized by dry mouth and dry eyes)

---Enhance cognitive functioning in some individuals with Alzheimer's disease

---Prevent development of cataracts and macular degneration

---Slow down motor impairment in amyotrophic lateral sclerosis (ALS, often called Lou Gehrig's disease which is a progressive loss of control of voluntary muscles due to destruction of nerve cells in the brain and spinal cord)

---Help treat hepatitis C when combined with standard medical treatment

---Increase HDL cholesterol (the good kind of cholesterol).

---Further studies are needed to confirm these early findings.

Dietary Sources
The body synthesizes cysteine from the essential amino acid methionine. Cysteine is also found in most high-protein foods including ricotta, cottage cheese, yogurt, pork, sausage meat, chicken, turkey, duck, luncheon meat, wheat germ, granola, and oat flakes.

Available Forms
•             NAC aerosol spray (prescription)
•             NAC liquid solution (prescription)
•             NAC topical solution
•             L-cysteine powder
•             Cysteine/NAC tablets or capsules

How to Take It
NAC is administered either intravenously or orally in the hospital to treat acetaminophen (paracetamol) poisoning in both children and adults. Acetaminophen poisoning is a medical emergency and treatment must be started within eight hours of an overdose.

Pediatric
There is no specific pediatric recommendation for cysteine. If laboratory tests reveal that the child has an amino acid imbalance that requires treatment, a healthcare provider may recommend a complete amino acid supplement that contains cysteine.

Adult
Recommended adult doses of NAC vary depending on the health condition being treated. The following list provides guidelines for the most common uses.

Respiratory illness: 200 mg two times per day for chronic bronchitis. ARDS is a medical emergency and is treated in the intensive care unit in the hospital with intravenous NAC as part of a comprehensive treatment regimen.

Antioxidant protection/general health: 500 mg per day to start. Dosage may be increased, with expert guidance. Someone with HIV/AIDS may be put on a dose as high as 4,000 mg per day. Adding a multivitamin will ensure that you are getting the B vitamins you need when taking NAC.

Precautions
Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable healthcare provider.

Some forms of cysteine are toxic and should be avoided. These include D-cysteine, D-cystine, and 5-methyl cysteine.

NAC may raise levels of homocysteine, an amino acid believed to play a role in the development of heart disease. Be sure to have your health care provider check your homocysteine level if you are taking NAC.

Extremely high doses (more than 7 grams) of cysteine should be avoided because it may be toxic to human cells and may even lead to death.

Oral NAC may cause nausea, vomiting, and diarrhea.

Intravenous administration of NAC (to treat, for example, acetaminophen poisoning) may cause severe allergic reactions, even angioedema (significant swelling of the soft tissue just beneath the skin including the face, lips, and around the eyes) or anaphylaxis (a life-threatening allergy that leads to inability to breath). Plus, there has been one case report of seizures from intravenous administration of NAC to a young girl for paracetamol intoxication.

Cysteine supplements should not be taken by individuals with cystinuria, a kidney condition in which excessive amounts of cysteine (along with three other amino acids) are lost in the urine.

Possible Interactions
If you are currently being treated with any of the following medications, you should not use cysteine supplements without first talking to your healthcare provider.

Blood Pressure Medications, Angiotensin-converting Enzyme (ACE) Inhibitors
NAC may enhance the blood pressure-lowering effects of ACE inhibitors, medications commonly used to treat high blood pressure. Examples of ACE inhibitors include benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, quenipril, ramepril, and trandolapril.

Immunosuppressive Medications
Treatment with NAC may enhance the effectiveness of immunosuppressive medications such as azathioprine, cyclophosphamide, prednisolone, or prednisone. More research in this area is needed.

Cisplatin and Doxorubicin
Laboratory and animal studies have suggested that NAC may reduce the toxic effects associated with both cisplatin and doxorubicin, medications used to treat a variety of cancers. However, scientific studies are needed to see if these effects apply to people.

Nitroglycerin and Isosorbide
Although NAC may enhance the effectiveness of nitroglycerin and isosorbide (two medications commonly used to treat chest pain), this combination may also increase the risk of side effects such as severe headaches and may lead to abnormally low blood pressure.

Oxiconazole
Topical applications of NAC may increase the effectiveness of oxiconazole, an antifungal medication used for athlete's foot.

Supporting Research
Adair JC, Knoefel JE, Morgan N. Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease. Neurology . 2001;57(8):1515-1517.
Ames BN. Micronutrient deficiencies: A major cause of DNA damage. Ann NY A