Hemangiosarcoma in Dogs Herbal and Holistic Treatments

Dog Hemangiosarcoma

Canine hemangiosarcoma is an incurable tumor of cells that line blood vessels (endothelial cells). Based on current estimates of the lifetime risk of cancer in dogs and the prevalence of hemangiosarcoma, we predict that of 65 million pet dogs living in the United States today, as many as two million may get this cancer and die from it. Although dogs of any age and breed are susceptible to hemangiosarcoma, it occurs more commonly in dogs beyond middle age, and in breeds such as Golden Retrievers, German Shepherd Dogs, Portuguese Water Dogs, and Skye Terriers, among others. 

Hemangiosarcoma develops slowly and is essentially painless – so clinical signs are usually not evident until the advanced stages when the tumors are resistant to most treatments. Less than 50% of dogs treated with standard-of-care for this tumor (surgery and intensive chemotherapy) survive more than six months. Many dogs die from severe internal bleeding before there is an opportunity to institute treatment. 

DIAGNOSIS/INITIAL EVALUATION

Because these tumors arise in internal organs there is often little warning that they are present prior to time they cause severe clinical signs of disease. A common estimate of the average time from discovery of the tumor until death occurs in affected dogs is six to eight weeks but death occurs more rapidly than this in a number of cases.
Visible bleeding, usually in the form of nosebleeds, and signs associated with blood loss, such as tiring easily, episodes of unexplained weakness, pale color to the mucous membranes of the mouth and eyes, increased respiratory rates, abdominal swelling and depression are the most common presenting signs for patients with hemangiosarcoma. A few dogs just suddenly die with no clinical signs having been noted by their families prior to death. Bleeding disorders associated with hemangiosarcoma are sometimes confused with immune mediated hemolytic anemia (IMHA) because the type of anemia caused by the two conditions is very similar and early clinical signs are often very similar, as well. Hemangiosarcomas can cause very large tumors, sometimes as large as ten or more pounds, when they affect the spleen.

In most instances tumors of this size in this location are found on physical exam. In other cases the tumor affects the heart and is hard to find on a physical exam and even easy to miss or X-rays. Sometimes there are hundreds of small tumors spread throughout the body and surgical exploration or an autopsy are the only ways to identify the problem.
The blood disorder that most commonly accompanies the presence of hemangiosarcoma tumors is disseminated intravascular coagulation (DIC). This is blood clotting that is occurring inappropriately inside the blood vessels. It uses up all of the blood clotting elements rapidly and dogs with this condition usually have platelet deficiencies, increased blood clotting times, decrease in fibrin content in the blood and an increase in fibrin degradation products (FDPs). This is probably the cause of death in most dogs affected with hemangiosarcoma.
Diagnosis of hemangiosarcoma can be accomplished in a number of ways. Identification of a tumor in the spleen or heart raises a high degree of suspicion for this tumor. Abdominal swelling is also highly suggestive in an older large breed dog. If fluid is aspirated from the abdomen and it looks like blood it is even more suggestive of hemangiosarcoma. If blood is drawn and will not clot when left in the syringe it is another sign that a dog may have this tumor. In some cases careful evaluation of the type of bleeding disorder present is necessary to raise the suspicion of hemangiosarcoma.
Canine hemangiosarcoma is among the most challenging and mysterious diseases encountered in veterinary practice. It is an incurable tumor of cells that line blood vessels, called vascular endothelial cells. Hemangiosarcoma is relatively common in dogs; it is estimated that this type of cancer accounts for 5-7% of all tumors seen in dogs. Considering the lifetime risk of cancer for dogs is between 1 in 2 and 1 in 3, we can calculate that 1.5 to 2.5 million of the ~72 million pet dogs in the United States today will get hemangiosarcoma and succumb from it. (WHAT!?) 

Although dogs of any age and breed are susceptible to hemangiosarcoma, it occurs more commonly in dogs beyond middle age (older than 6 years), and in breeds such as Golden Retrievers, German Shepherd Dogs, Portuguese Water Dogs, Bernese Mountain Dogs, Flat Coated Retrievers, Boxers and Skye Terriers, among others. According to the Golden Retriever Health Study published in 2000, the estimated lifetime risk of hemangiosarcoma in this breed is 1 in 5, illustrating the magnitude of this problem.

Unlike other cancers, hemangiosarcoma is almost an exclusive disease of dogs. In dogs, the common primary sites for hemangiosarcoma are the spleen, the right atrium of the heart, and the subcutis, which is the tissue beneath the skin. The pattern of growth for these tumors involves infiltration into normal tissues surrounding the tumor as well as distant spread (metastasis). The disease is indolent; in other words, it does not cause pain and the rate of growth in the early stages is relatively slow. Dogs harboring even large hemangiosarcomas may show no clinical signs or evidence that they have a life threatening disease. Generally, the tumor cells retain some normal aspects of behavior, so they try to make blood vessels. But these vessels are tortuous and malformed, and blood cells tend to pool in them and clot. The clots then prevent blood and nutrients from reaching tumor cells, in turn causing them to die. This creates small ruptures in the tumor through which blood may escape into the abdomen, heart sac, chest, or subcutaneous space. Depending on the amount of blood lost, affected dogs may show non-specific (constitutional) signs such as lethargy and weakness, but these are transient and resolve as dogs reabsorb the blood components and make new blood cells. The clinical signs are recurrent, but they also are subtle enough to go unnoticed for some time. Since hemangiosarcoma tends to metastasize aggressively to lungs, liver, intestines, and the membranous connective tissue that supports the intestines), distant spread (either microscopic or macroscopic) has inevitably occurred once the disease is finally diagnosed. The eventual outcome for patients with this disease often follows the rupture of a large or rapidly growing tumor, which results in acute, severe hemorrhage, collapse, shock, and death.

What Causes Hemangiosarcoma
We do not precisely know what causes canine hemangiosarcoma. The observations that the disease occurs more commonly in dogs than in other animals, and that some breeds are at higher risk than others tell us that heritable factors must contribute to risk. Tumors arise when cells accumulate mutations that eliminate normal constraints of growth and genetic integrity. These mutations provide cells a selective growth advantage within their environment, essentially the same evolutionary phenomenon that we call natural selection, albeit on a microscopic scale. Most mutations arise because the enzymes that control cell division are not foolproof. 
Fortunately, most of these mutations are silent (they neither help nor hurt the cell or the organism), and the body has mechanisms to eliminate most cells that acquire deleterious mutations. 
We have identified some of the fundamental properties of canine hemangiosarcoma, and it is possible one or more of these may prove to be an “Achilles heel” for the tumor. For example, most of these tumors make growth factors that they need to survive, or they “coerce” cells in their environment to do this for them. One of these growth factors is vascular endothelial growth factor-A or VEGF, which acts by binding specific receptors on the hemangiosarcoma cells. New drugs under development by various pharmaceutical companies are designed specifically to interfere with the signals transmitted by these receptors. The reliance of hemangiosarcoma cells on VEGF signals to survive should make them more sensitive than normal cells to these drugs. Several groups are working to bring these drugs into the clinic, but the process is slow because testing must be done in a careful, deliberate way to ensure the compounds are safe and effective. 

Standard Treatment for Canine Hemangiosarcoma
Standard Treatment and prognosis for Hemangiosarcoma vary by location. Cutaneous Hemangiosarcoma is often curable with surgery alone, provided the lesion is small and confined to the dermis. Cutaneous  Hemangiosarcoma often occur in areas of glabrous skin on lightly pigmented dogs and arise as a result of sunlight exposure.Lesions that are larger or deeper may be either primary or metastatic lesions and warrant more aggressive treatment. Treatment of splenic, atrial, or subcutaneous Hemangiosarcoma consists of surgical excision of the primary tumor and adjuvant chemotherapy. Recommended chemotherapy for Hemangiosarcoma is single-agent doxorubicin, intravenously given every 3 weeks. Use of an indwelling catheter is important because of the catastrophic tissue slough that occurs after doxorubicin extravasation. Owners should be warned of the potential of cardiotoxicity. A total of 4-6 doses of doxorubicin are recommended. Median survival time after surgery alone is reported to be 2-3 months, with the addition of chemotherapy increasing the median survival time to 4-6 months. The VAC protocol may be useful; however it has a higher morbidity rate with no increase in survival time. Dogs with splenic Hemangiosarcoma that have ruptured may have a poorer prognosis than those not ruptured. Currently several drugs are being investigated for their antiangiogenic properties, and may be useful for treatment of Hemangiosarcoma in the future. Follow-up for Hemangiosarcoma should include monthly thoracic radiographs and physical examinations.
Regrettably, the standard-of-care for this disease has not seen significant advancement over the past 20 or 30 years. There is presently no readily available, effective test for early diagnosis of hemangiosarcoma. Careful analysis of blood samples by experienced pathologists may hint at the presence of chronic hemorrhage and blood vessel abnormalities that are suggestive of hemangiosarcoma. However, this method is neither sensitive nor specific to confirm the diagnosis. Non-invasive imaging methods are useful aids to diagnose the disease. In particular, ultrasound is moderately specific, but it is not sensitive, and the tumor must be large enough to be grossly visible. In addition, biopsies are required for confirmation of imaging results. Repeated biopsies of tissues where the tumors may arise (without other evidence for the presence of a tumor) are of little use to provide early diagnosis, and considering the fact that there is some risk to these procedures, such an approach is practically and ethically unacceptable.
The options for therapy of canine hemangiosarcoma are limited, largely because the disease is not diagnosed until the late stages. The conventional standard treatment consists of surgery to shrink or remove the primary tumor, when possible, followed by intensive chemotherapy. In some cases, surgery is not feasible, or it can be impractical or inappropriate (for example, if there is evidence of extensive metastatic spread to sites beyond the primary tumor). Median survival for dogs treated with surgery alone is approximately 90 days, and that is extended to approximately 180 days by the addition of chemotherapy using one of several protocols available. Because the goal for chemotherapy in pet dogs is to extend life with good quality, toxicity is generally not a major issue of concern(WHAT?!), and when it occurs it is most often managed without much difficulty.

Surgery and chemotherapy have limited success in prolonging survival times and increasing quality of life in dogs with HSA. Splenectomy alone gives an average survival time of 1–3 months. Advances in medical oncology are resulting in increased survival rates and a better quality of life for veterinary cancer patients. An understanding of mechanisms of metastasis has led to the development of new treatments designed to delay or inhibit tumor spread. Promising new treatment options include novel delivery systems (inhalation or intracavitary chemotherapy); use of immunomodulators such as liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine; antimetastatic agents such as inhibitors of angiogenesis (interferons, thalidomide), matrix metalloproteinase inhibitors, and minocycline; dietary modifications; and gene therapy. Inhibitors of angiogenesis (meaning anti-angiogenesis) seem to be safe and, unlike conventional chemotherapy, do not induce drug resistance. Although many of the newer approaches are still under development and review, the use of multimodality therapy incorporating innovative treatment modalities may offer the best therapeutic option for dogs affected with HSA.

The nature of hemangiosarcoma itself draws attention to the prolific formation of blood vessels through the tumors. These vessels typically rupture causing loss of blood internally. Yun Nan Bai Yao herbs really helps slow the bleeding. As another integral part of natural healing for hemangiosarcoma is to help prevent the formation of new blood vessels with anti-angiogenesis supplements. Powerful medicinal mushrooms have been shown to discourage the rapid growth of these blood vessels and support the immune system. 

A basic start I have seen people using is:

A dog cancer diet – See Diets for dog cancer at top of page or search box

Yunnan Baiyao – not only does it control bleeding but also seems to slow this cancer down.

Medicinal Mushrooms and Beta Glucans
Mushrooms have been used in traditional Chinese medicine for more than 2,000 years. The compound in the mushroom that is believed to have immune-boosting properties is polysaccharopeptide, or PSP. In the last two decades, some studies have suggested that PSP Beta glucans also has a tumor-fighting effect. Read about medicinal Mushrooms and Beta Glucans below.

Chai Hu Jia Long Gu Mu Li Tang with a good amount of added Dang Gui and San Qi. This is the magic ingredient which makes this protocol work, in my opinion. And you need the added ingredients. It is not available with the additives commercially. This formula is now available from a etsy store Kingdom of Basil however you need to be working with a holistic vet or a western vet open to alternative medicine if you use it. Large amounts of Dang Gui can cause diarrhea and often this formula needs to be supplemented with something if it does. You need the San Qi to control the bleeding with this cancer. In addition you need to make sure that this formula uses ginseng (Ren Shen) and not Dang Shen. Chai Hu Jia Long Gu Mu Li Tang contains the root formula Xiao Chai Hu Tang which is used quite often for cancer.

IP6 – this supplement is important in stimulating the immune system’s natural killer cells to destroy cancer tissue. It is an antioxidant and has effects in inhibiting cancer cell growth and division. Not much research has been done in humans with this supplement but a lot of cancer studies have been done in animals.
Many dose dogs at 800-1600mg twice a day.

More then any other cancer I work with I think this is the most important one to make sure you have a good holistic vet on board. I know, I know I have said that a few times already.

• Astragalus

 "I saw this thread and just joined the boards so I could give you a little information. Our lab was diagnosed with this disease on March 8. He was given 1 month to live (large spleen tumor and spread to the liver) but has been doing okay. No additional bleeding, no weight loss, pink gums etc. The oncologist said we could have the spleen removed (but the cancer would remain since it had spread) and do chemo (they would not do chemo without the surgery); this might extend his life by a few months but we felt the pain and stress with little extension of live was not worth it for him. The vet oncologist put him on a Chinese herb called Yunnan payio/baiyo that inhibits bleeding (2 capsules 2 times a day for an 80 lb dog). We can get this from the vet or order online (cheaper). We also give many other supplements and feed a high protein, no grain diet with supplements of omega 3 fatty acids. Other supplements include milk thistle (for the liver), immune support, anemia meds, medicinal mushrooms, and others. "

Mushroom Derived Compound Lengthens Survival in Dogs With Cancer

Mushroom-Derived Compound Lengthens Survival in Dogs With Cancer, Study Suggests


 Dogs with hemangiosarcoma that were treated with a compound of Beta glucans derived from the Coriolus versicolor mushroom had the longest survival times ever reported for dogs with the disease. These promising findings offer hope that the compound may one day offer cancer patients -- human and canine alike -- a viable alternative or complementary treatment to traditional chemotherapies.


The study was conducted by two University of Pennsylvania School of Veterinary Medicine faculty. They published their findings in an open-access article in the journal Evidence-Based Complementary and Alternative Medicine.

The Coriolus versicolor mushroom, known commonly as the Yunzhi or Turkey Tail mushroom, has been used in traditional Chinese medicine for more than 2,000 years. The compound in the mushroom that is believed to have immune-boosting properties is polysaccharopeptide, or PSP. In the last two decades, some studies have suggested that PSP Beta glucans also has a tumor-fighting effect.

"There have been a series of studies looking at groups of people with cancer,"  "The issue with those studies is that they weren't necessarily measuring what most people would think is the most clinically important result, which is, do people taking PSP Beta glucans live longer?"

To address this critical question,University of Pennsylvania School of Veterinary Medicine pursued a study in dogs with naturally occurring hemangiosarcoma, an aggressive, invasive cancer that arises from the blood cells and typically affects the spleen. It commonly strikes golden retrievers and German shepherds.

Fifteen dogs that had been diagnosed with hemangiosarcoma participated in the trial. Divided into three groups of five, each group received a different dose -- 25, 50 or 100 mg/kg/day -- of (Beta glucans), a formulation of PSP.

The owners were instructed to give their dog capsules of (Beta glucans), compounded by Penn pharmacists, daily. Each month, the owners brought their dogs to Penn's Ryan Veterinary Hospital for follow-up visits. There, the researchers took blood samples and conducted ultrasounds to determine the extent that tumors developed or grew and spread in the dogs' bodies.

Based on the ultimate endpoints -- how quickly the tumors progressed and how long the dogs actually lived -- the results of the researchers' trial suggest that the Beta glucans was effectively fighting the tumors.

"We were shocked," University of Pennsylvania School of Veterinary Medicine said. "Prior to this, the longest reported median survival time of dogs with hemangiosarcoma of the spleen that underwent no further treatment was 86 days. We had dogs that lived beyond a year with nothing other than this mushroom as treatment."

There were not statistically significant differences in survival between the three dosage groups, though the median survival time was highest in the 100 mg group, at 199 days, eclipsing the previously reported median survival time.

The results were so surprising, in fact, that the researchers asked Penn Vet pathologists to recheck the dogs' tissue biopsies to make sure that the dogs really had the disease.

"They reread the samples and said, yes, it's really hemangiosarcoma," University of Pennsylvania School of Veterinary Medicine said.

Chemotherapy is available for treating hemangiosarcoma, but many owners opt not to pursue that treatment once their dog is diagnosed. "It doesn't hugely increase survival, it's expensive and it means a lot of back and forth to the vet for the dog," Cimino Brown said. "So you have to figure in quality of life."

 As an added benefit, University of Pennsylvania School of Veterinary Medicine have found no evidence of adverse effects from the Beta glucans treatment.

 "Although hemangiosarcoma is a very sad and devastating disease, in the long term, if we prove that this works, this treatment can be a really nice alternative for owners to have increased quality time with their pet at the end of its life."

Evid Based Complement Alternat Med. 2012;2012:384301. doi: 10.1155/2012/384301. Epub 2012 Sep 5.

Single agent polysaccharopeptide delays metastases and improves survival in naturally occurring hemangiosarcoma.
Brown DC, Reetz J.

Source

Veterinary Clinical Investigations Center, Department of Clinical Studies, School of Veterinary Medicine and University of Pennsylvania, 3900 Delancey Street, Philadelphia, PA 19104-6010, USA.

Abstract

The 2008 World Health Organization World Cancer Report describes global cancer incidence soaring with many patients living in countries that lack resources for cancer control. Alternative treatment strategies that can reduce the global disease burden at manageable costs must be developed. Polysaccharopeptide (PSP) is the bioactive agent from the mushroom Coriolus versicolor. Studies indicate PSP has in vitro antitumor activities and inhibits the growth of induced tumors in animal models.  The investment of resources required to complete large-scale, randomized controlled trials of PSP in cancer patients is more easily justified if antitumor and survival benefits are documented in a complex animal model of a naturally occurring cancer that parallels human disease. Because of its high metastatic rate and vascular origin, canine hemangiosarcoma is used for investigations in antimetastatic and antiangiogenic therapies. In this double-blind randomized multidose pilot study, high-dose PSP Beta Glucans significantly delayed the progression of metastases and afforded the longest survival times reported in canine hemangiosarcoma. These data suggest that, for those cancer patients for whom advanced treatments are not accessible, PSP as a single agent might offer significant improvements in morbidity and mortality.

[Study on effects of Astragalus, Angelica and their combination on vascular endothelial cell proliferation in vitro].

[Article in Chinese]
Lei Y, Gao Q, Li YS.
Source

Xiyuan Hospital, China Academy of TCM, Beijing 100091.

Abstract

OBJECTIVE:

To study the effects of Astragalus membranaceus (AM), Angelica sinensis (AS) and their combination on human umbilical vein endothelial cell (HUVEC) proliferation and cells cycle.

METHODS:

The effects were observed and studied by means of taking the cultured HUVECs as model to determine the cell proliferation with MTT method, cell cycle was analyzed with cytometry, and vascular endothelial growth factor (VEGF) expression with SABC method. The regulatory effects of AM, AS and their combination on the HUVEC proliferation promoting were observed and studied.

RESULTS:

AM and AS, used singly or in combination, could promote the growth of endothelial cells, increase the cell population in S phase, the effects showed more significant when used in combination (P < 0.05 or P < 0.001). Meanwhile, VEGF expression in all the medicated group was up-regulated, but in the PBS control group, it showed only weak expression (P < 0.05 or P < 0.01).

CONCLUSION:

AM and AS have effect in promoting vascular endothelial cell proliferation and DNA synthesis, and showed synergistic effect when they were used in combination, suggesting that these two Chinese herbs could have certain effect on the genesis and development of neogenetic vascularization in ischemic myocardium.

.

from akc on hemangiosarcoma

"We also looked for trends in HSA occurrence compared with lymphomas. Dog lymphosarcomas have remained fairly constant, at about 1.5% of diagnoses, while canine HSAs have increased from less than 1% to approximately 1.5%. The location of canine HSA was found to be the skin in 32.8% of all HSA cases, the spleen in 28.8% of cases, and the heart in only 7.1% of cases. The tumors were diagnosed with a female-male ratio of 41:56 percent. The breeds of highest incidence were the Saluki (32/73), Golden Retriever (119/5196), German Shepherd Dog (37/2796), Labrador Retriever (47/5159), and Boxer (16/2033). The average age of dogs in HSA cases was 9 years, while it was roughly 11 years for the Saluki."

" An understanding of mechanisms of metastasis has led to the development of new treatments designed to delay or inhibit tumor spread. Promising new treatment options include novel delivery systems (inhalation or intracavitary chemotherapy); use of immunomodulators such as liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine; antimetastatic agents such as inhibitors of angiogenesis (interferons, thalidomide), matrix metalloproteinase inhibitors, and minocycline; dietary modifications; and gene therapy. Inhibitors of angiogenesis seem to be safe and, unlike conventional chemotherapy, do not induce drug resistance. "

"The distinction between a haematoma, a haemangioma and a haemangiosarcoma is of very great significance if a surgical procedure is to be carried out. The former two present little threat as a result of contamination during surgery whilst a haemangiosarcoma presents a very severe threat. The removal of a haemangiosarcoma is extremely hazardous as any blood or tissue contamination of other organs or of the abdominal cavity will almost certainly result in seeding of neoplastic cells. "

"Radiographs or X-rays can be of help diagnosing the presence of the tumor but again an ultrasound image will give you an almost immediate confirmation . More importantly it will also indicate to you how far the disease has progressed in term of metastasis to other organs."also shows pictures

"The spleen is attached to the stomach by the gastrosplenic ligament

The spleen has a tremendous blood supply

The spleen has filters which cleanse the blood

Dogs and cats can function normally without a spleen

Clinical signs of diseases of the spleen

Pale gums – due to bleeding into the abdomen from a ruptured tumor

Distention of the abdomen

Weakness

Loss of appetite

Hemangiosarcoma, the most common type of tumor of the spleen is highly malignant

Most dogs with this disease have microscopic spread of the tumor to the lungs, liver, heart or other regions of the body

Chemotherapy and surgery can increase the survival to about 1 year with hemangiosarcoma of the spleen if macroscopic spread is not present

"Since the tumor usually grows on a highly vascular organ such as a spleen or liver ,when it ruptures it results in a sudden abdominal bleed in the affected pet. Since the blood loss is contained within the body the owner never notices it .This correlated to the weak phase whereby the pet owner sees their pet as " off " .Again since the blood is not really lost it is reabsorbed within a few days by the dog hence giving it back it's strength .The problem is that with each bleeding episode the dog is effectively seeding it own body with new sites for the tumors to grow anew."

Electrochemotherapy: potentiation of local antitumour effectiveness of cisplatin in dogs and cats. This study showed that electrochemotherapy with cisplatin is an effective, safe and simple local treatment of different histological types of cutaneous and subcutaneous (on skin or just below skin) tumors in cats and dogs.          

 

Milk Thistle Silymarin Silybin for Cancer

Questions and Answers About Milk Thistle

    What is milk thistle?

    Milk thistle is a plant whose fruit and seeds have been used for more than 2,000 years as a treatment for disorders of the liver, bile ducts, and gallbladder. Milk thistle is native to Europe but can also be found in the United States and South America.

    The medicinal ingredient found in milk thistle is silymarin, an extract of milk thistle seeds. It is an antioxidant that protects against cell damage. Silymarin contains 4 compounds: silybin (the most active), isosilybin, silychristin, and silydianin. Most research has studied silymarin or its major compound silybin, instead of the plant in its whole form.

    The botanical name for milk thistle is Silybum marianum. Milk thistle is also called holy thistle, Marian thistle, Mary thistle, St. Mary thistle, Our Lady's thistle, wild artichoke, Mariendistel (German), and Chardon-Marie (French).

    What is the history of the discovery and use of milk thistle as a complementary and alternative treatment for cancer?

    The ancient Greeks and Romans used milk thistle as a treatment for liver ailments and snake bites. During the Middle Ages, milk thistle was recommended to treat liver toxins.  The German Commission E, which studies the safety and efficacy of herbs for the German government, recommends milk thistle for liver damage due to toxins, cirrhosis of the liver, and as a supportive therapy for chronic inflammation of the liver.

    Despite milk thistle's long history of use for liver complaints, it was not until 1968 that researchers extracted silymarin from milk thistle seeds and suggested that it might be the plant's active ingredient. Silymarin was later discovered to be a mixture of flavonolignans, a family of plant-based substances with antioxidant effects.






Milk Thistle Shows Promising Applications in Treating Liver Disease, Cancer


When the Romans prescribed milk thistle 2,000 years ago, they did so for a variety of health concerns, including serpent bites, melancholy, plague and milk production, in addition to “carrying off bile.”1,2    Now, the popularity of milk thistle is soaring, not only for treating chronic liver problems for which it is best known, but also for its ability to protect other organs from the damaging effects of radiation, chemotherapy, other xenobiotics and chronic disease.3   For example, its antioxidant actions decrease gentamicin-induced nephrotoxicity in dogs;4   milk thistle also promotes kidney function in patients with end-stage diabetic nephropathy.5 
  
What’s in It
Milk thistle extract,  the first substance extracted from the crushed seeds, contains up to 80 percent silymarin, the main active constituent.6  In contrast, the silymarin content of unprocessed seeds may fall as low as 4 percent silymarin.7   Some manufacturers standardize the silymarin content to ensure equivalence between batches. Silibinin (or silybin), a semi-purified fraction of silymarin, acts as an important marker for research to track pharmacokinetics and ensure adequate plasma and target tissue concentrations.8  Monitoring pharmacokinetics becomes especially important when studying phytomedicinals exhibiting poor or erratic bioavailability, as do the flavonolignans comprising silymarin.  Complexing silibinin with phophatidylcholine dramatically improves oral availability; manufacturers may also add vitamin E and zinc to further manage liver dysfunction--doing so does not attenuate bioavailability .9

Working for the Liver
The plant stimulates liver repair and detoxification through four main avenues: 
1. antioxidation, free radical scavenging and glutathione regulation; 
2. stabilization of cell membranes and permeability, which limits hepatotoxin entry into hepatocytes; 
3. ribosomal RNA synthesis promotion, stimulating liver regeneration; and 
4. slowing transformation of stellate hepatocytes into myofibroblasts, slowing the onset of cirrhosis arising through collagen deposition.10

New Applications for Cancer
The most salient new applications for milk thistle arise in its role as an adjunct for cancer chemoprevention, treatment and to reduce side effects of treatment.11,12    Specifically, silymarin has led to reductions in tumor incidence and the number of chemically-induced tumors in rat models for colon, tongue and bladder cancer. It has also held back the growth of human prostate cancer and lung cancer xenografts in mice bred as immunodeficient.13  Milk thistle derivatives protect the kidneys from radiation injury and cisplatin nephrotoxicity14,15    and may protect the heart from doxorubicin-induced lipid peroxidation. When combined with omega 3 fatty acids, milk thistle has reduced the number of radionecrosis sites in cancer patients and prolonged survival.16  Milk thistle potentiated antitumor effects of drugs like cisplatin in both in vivo and in vitro studies.17   



Adverse Effects
Milk thistle’s ability to promote liver regeneration you might think it could conceivably stimulate tumor growth in cases of hepatocellular carcinoma,22  but  studies showed that milk thistle demonstrated strong anticancer (pro-apoptotic and growth-inhibiting) activity against human hepatocellular carcinoma cells.23   

Overall, the majority of patients tolerate even high doses of milk thistle; as with most herbs, adverse effects typically involve mild gastrointestinal upset at initial dosing.  





    What is the theory behind the claim that milk thistle is useful in treating cancer?

    To research the claim that milk thistle is useful in treating cancer, its active substance silymarin and its major compound silybin have been the most widely studied ingredients.

    Silymarin and silybin may protect the liver against damage from toxic chemicals by blocking toxins from entering the cell or by moving toxins out of the cell before damage begins.

    Silymarin and silybin have been studied in the laboratory in cancer cells as well as in animal tumors of the tongue, skin, bladder, colon, and small intestine. They have been tested for their potential to:

        Make chemotherapy less toxic.
        Make chemotherapy more effective.
        Stop or slow the growth of cancer cells and block tumors from starting or continuing to grow.
        Help to repair liver tissue.

    In Europe, the active compound silybin is given by intravenous infusion as the only effective antidote for Amanita phalloides, a rare mushroom toxin that causes deadly liver failure.

    Most milk thistle supplements are measured by how much silybin they contain. 

    Have any preclinical (laboratory or animal) studies been conducted using milk thistle?

    Research in a laboratory or using animals is done to find out if a drug, procedure, or treatment is likely to be useful in humans. Preclinical studies are done before clinical trials (in humans) are begun.

    Silymarin, the active substance found in milk thistle seeds, has been studied in laboratory research. These studies have shown that it acts as an antioxidant by:

        Strengthening cell walls to prevent toxins from crossing into the cell.
        Stimulating enzymes that make toxins less harmful to the body.
        Blocking damaging substances called free radicals from attacking cells.

    Silybin, the major compound found in silymarin, has been studied in laboratory experiments using cancer cell lines (cells adapted to grow in the laboratory). These studies show that silybin:

        May help cisplatin and doxorubicin (chemotherapy drugs) work better against ovarian and breast cancer cells.
        May have direct anticancer effects against prostate, breast, and cervical cancer cells.
        May slow down cell growth, as shown in prostate cancer cell lines.

    In laboratory tests using rat livers, silymarin and silybin have also been found to boost the regrowth of liver tissue.

    Tests on colorectal cancer cells transplanted into mice found that silybin given twice a day decreased tumor growth.

    Have any clinical trials (research studies with people) of milk thistle been conducted?

    There is 1 case report describing the use of silymarin in a patient with promyelocytic leukemia who required breaks in chemotherapy due to abnormal liver enzyme levels. During 4 months of treatment with silymarin, the patient had normal liver enzyme levels and was able to undergo chemotherapy without breaks. A second case report describes a patient with hepatocellular carcinoma whose symptoms improved when he took 450 milligrams of silymarin per day, without anticancer therapy.

    A randomized clinical trial in children with acute lymphoblastic leukemia found that silymarin decreased the harmful effects of chemotherapy on the liver without working against the cancer treatment. The children taking silymarin needed fewer chemotherapy dose reductions because of side effects than the children who did not take milk thistle.

    A number of clinical trials have studied milk thistle or silymarin in the treatment of patients with hepatitis, cirrhosis, or disorders of the bile ducts.  In a trial of biologic therapy for patients with chronic hepatitis, patients taking silymarin had fewer symptoms and a better quality of life compared to patients not taking silymarin. 


References

1. PDR® for Herbal Medicines™. 2nd ed. Montvale, NJ: Medical Economics, 2000. 
2. Lee DY, Liu Y: Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle). J Nat Prod 66 (9): 1171-4, 2003.  [PUBMED Abstract]
3. Hruby K, Csomos G, Fuhrmann M, et al.: Chemotherapy of Amanita phalloides poisoning with intravenous silibinin. Hum Toxicol 2 (2): 183-95, 1983.  [PUBMED Abstract]
4. Wagner H, Hörhammer L, Münster R: [On the chemistry of silymarin (silybin), the active principle of the fruits from Silybum marianum (L.) Gaertn. (Carduus marianus L.)] Arzneimittelforschung 18 (6): 688-96, 1968.  [PUBMED Abstract]
5. Campos R, Garrido A, Guerra R, et al.: Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med 55 (5): 417-9, 1989.  [PUBMED Abstract]
6. Farghali H, Kameniková L, Hynie S, et al.: Silymarin effects on intracellular calcuim and cytotoxicity: a study in perfused rat hepatocytes after oxidative stress injury. Pharmacol Res 41 (2): 231-7, 2000.  [PUBMED Abstract]
7. Lettéron P, Labbe G, Degott C, et al.: Mechanism for the protective effects of silymarin against carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice. Evidence that silymarin acts both as an inhibitor of metabolic activation and as a chain-breaking antioxidant. Biochem Pharmacol 39 (12): 2027-34, 1990.  [PUBMED Abstract]
8. Zhao J, Agarwal R: Tissue distribution of silibinin, the major active constituent of silymarin, in mice and its association with enhancement of phase II enzymes: implications in cancer chemoprevention. Carcinogenesis 20 (11): 2101-8, 1999.  [PUBMED Abstract]
9. Valenzuela A, Guerra R, Videla LA: Antioxidant properties of the flavonoids silybin and (+)-cyanidanol-3: comparison with butylated hydroxyanisole and butylated hydroxytoluene. Planta Med (6): 438-40, 1986.  [PUBMED Abstract]
10. Valenzuela A, Guerra R, Garrido A: Silybin dihemisuccinate protects rat erythrocytes against phenylhydrazine-induced lipid peroxidation and hemolysis. Planta Med 53 (5): 402-5, 1987.  [PUBMED Abstract]
11. Valenzuela A, Aspillaga M, Vial S, et al.: Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Med 55 (5): 420-2, 1989.  [PUBMED Abstract]
12. Mira ML, Azevedo MS, Manso C: The neutralization of hydroxyl radical by silibin, sorbinil and bendazac. Free Radic Res Commun 4 (2): 125-9, 1987.  [PUBMED Abstract]
13. Mira L, Silva M, Manso CF: Scavenging of reactive oxygen species by silibinin dihemisuccinate. Biochem Pharmacol 48 (4): 753-9, 1994.  [PUBMED Abstract]
14. Koch HP, Löffler E: Influence of silymarin and some flavonoids on lipid peroxidation in human platelets. Methods Find Exp Clin Pharmacol 7 (1): 13-8, 1985.  [PUBMED Abstract]
15. Garrido A, Arancibia C, Campos R, et al.: Acetaminophen does not induce oxidative stress in isolated rat hepatocytes: its probable antioxidant effect is potentiated by the flavonoid silybin. Pharmacol Toxicol 69 (1): 9-12, 1991.  [PUBMED Abstract]
16. Bosisio E, Benelli C, Pirola O: Effect of the flavanolignans of Silybum marianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. Pharmacol Res 25 (2): 147-54, 1992 Feb-Mar.  [PUBMED Abstract]
17. Altorjay I, Dalmi L, Sári B, et al.: The effect of silibinin (Legalon) on the the free radical scavenger mechanisms of human erythrocytes in vitro. Acta Physiol Hung 80 (1-4): 375-80, 1992.  [PUBMED Abstract]
18. Scambia G, De Vincenzo R, Ranelletti FO, et al.: Antiproliferative effect of silybin on gynaecological malignancies: synergism with cisplatin and doxorubicin. Eur J Cancer 32A (5): 877-82, 1996.  [PUBMED Abstract]
19. Bhatia N, Zhao J, Wolf DM, et al.: Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: comparison with silymarin. Cancer Lett 147 (1-2): 77-84, 1999.  [PUBMED Abstract]
20. Zi X, Agarwal R: Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: implications for prostate cancer intervention. Proc Natl Acad Sci U S A 96 (13): 7490-5, 1999.  [PUBMED Abstract]
21. Duthie SJ, Johnson W, Dobson VL: The effect of dietary flavonoids on DNA damage (strand breaks and oxidised pyrimdines) and growth in human cells. Mutat Res 390 (1-2): 141-51, 1997.  [PUBMED Abstract]
22. Vailati A, Aristia L, Sozzé E, et al.: Randomized open study of the dose-effect relationship of a short course of IdB 1016 in patients with viral or alcoholic hepatitis. Fitoterapia 64 (3), 219-28, 1993. 
23. Salmi HA, Sarna S: Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol 17 (4): 517-21, 1982.  [PUBMED Abstract]
24. Parés A, Planas R, Torres M, et al.: Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 28 (4): 615-21, 1998.  [PUBMED Abstract]
25. Moscarella S, Giusti A, Marra F, et al.: Therapeutic and antilipoperoxidant effects of silybin-phosphatidylcholine complex in chronic liver disease: preliminary results. Current Therapeutic Research 53 (1): 98-102. 
26. Marena C, Lampertico M: Preliminary clinical development of silipide: a new complex of silybin in toxic liver disorders. Planta Med 57 (Suppl 2): A124-5, 1991. 
27. Marcelli R, Bizzoni P, Conte D, et al.: Randomized controlled study of the efficacy and tolerability of a short course of IdB 1016 in the treatment of chronic persistent hepatitis. European Bulletin of Drug Research 1 (3): 131-5, 1992. 
28. Flisiak R, Prokopowicz D: Effect of misoprostol on the course of viral hepatitis B. Hepatogastroenterology 44 (17): 1419-25, 1997 Sep-Oct.  [PUBMED Abstract]
29. Ferenci P: [Therapy of chronic hepatitis C] Wien Med Wochenschr 150 (23-24): 481-5, 2000.  [PUBMED Abstract]
30. Buzzelli G, Moscarella S, Giusti A, et al.: Therapeutic effects of a new silybin complex in chronic active hepatitis (CAH). [Abstract] Hellenic Journal of Gastroenterology 5 (Suppl): A-151, 38, 1992. 
31. Albrecht M, Frerick H, Kuhn U, et al.: Therapy of toxic liver pathologies with Legalon®. Z Klin Med 47: 87-92, 1992.

Footnotes:

1. Mulrow C, Lawrence V, Jacobs B, et al. Milk thistle: effects on liver disease and cirrhosis and clinical adverse effects. Evid Rep Technol Assess. 2000. Chapter 1. Introduction. Obtained on 1-26-08 at http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1.section.29172.

2. Post-White J, Ladas EJ, and Kelly KM. Advances in the use of milk thistle (Silybum marianum). Integrative Cancer Therapies. 2007;6(2):104-109.

3. Greenlee H, Abascal K, Yarnell E, and Ladas E. Clinical applications of Silybum marianum in oncology.  Integrative Cancer Therapies. 2007;6(2):158-166.

4. Varzi HN, Esmailzadeh S, Morovvati H, et al. Effect of silymarin and vitamin E on gentamicin-induced nephrotoxicity in dogs. J Vet Pharmacol Therap. 2007;30:477-481.

5. Greenlee H, Abascal K, Yarnell E, and Ladas E. Clinical applications of Silybum marianum in oncology.  Integrative Cancer Therapies. 2007;6(2):158-166.

6. Kroll DJ, Shaw KS, and Oberlies NH. Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integrative Cancer Therapies. 2007;6(2):110-119.

7. Greenlee H, Abascal K, Yarnell E, and Ladas E. Clinical applications of Silybum marianum in oncology.  Integrative Cancer Therapies. 2007;6(2):158-166.

8. Kroll DJ, Shaw KS, and Oberlies NH. Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integrative Cancer Therapies. 2007;6(2):110-119.

9. Filburn CR, Kettenacker R, and Griffin DW.  Bioavailability of a silybin-phosphatidylcholine complex in dogs.  J Vet Pharmacol Therap.  2007;30:132-138.

10. Sagar SM. Future directions for research on Silybum marianum for cancer patients. Integrative Cancer Therapies.  2007;6(2):166-173.

11. Kroll DJ, Shaw KS, and Oberlies NH.  Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integrative Cancer Therapies. 2007;6(2):110-119.

12. Greenlee H, Abascal K, Yarnell E, and Ladas E. Clinical applications of Silybum marianum in oncology.  Integrative Cancer Therapies. 2007;6(2):158-166.

13. Malewicz B, Wang Z, Jiang C, et al. Enhancement of mammary carcinogenesis in two rodent models by silymarin dietary supplements. Carcinogenesis. 2006;27:1739-1747.

14. Greenlee H, Abascal K, Yarnell E, and Ladas E. Clinical applications of Silybum marianum in oncology.  Integrative Cancer Therapies.  2007;6(2):158-166.

15. Gaedeke J, Fels LM, Bokemeyer C, et al. cisplatin nephrotoxicity and protection by silibinin. Nephrol Dial Transplant. 1996;11(1):55-62.

16. Greenlee H, Abascal K, Yarnell E, and Ladas E. Clinical applications of Silybum marianum in oncology.  Integrative Cancer Therapies. 2007;6(2):158-166.

17. Greenlee H, Abascal K, Yarnell E, and Ladas E. Clinical applications of Silybum marianum in oncology.  Integrative Cancer Therapies.  2007;6(2):158-166.

18. Kroll DJ, Shaw KS, and Oberlies NH.  Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integrative Cancer Therapies. 2007;6(2):110-119.

19. Greenlee H, Abascal K, Yarnell E, and Ladas E. Clinical applications of Silybum marianum in oncology. Integrative Cancer Therapies.  2007;6(2):158-166.

20. Van Erp NPH, Baker SD, Zhao M et al. Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res. 2005;11(21):7800-7805.

21. Chauret N, Gauthier A, Martin J, et al.  In vitro comparison of cytochrome P450-mediated metabolic activities in human, dog, cat, and horse.  Drug Metabolism and Disposition. 1997;25(10):1130-1136.

22. Greenlee H, Abascal K, Yarnell E, and Ladas E.  Clinical applications of Silybum marianum in oncology.  Integrative Cancer Therapies. 2007;6(2):158-166.

23. Varghese L, Agarwal C, Tyagi A, et al. Silibinin efficacy against human hepatocellular carcinoma. Clin Cancer Res.  2005;11(23):8441-8448.

24. Malewicz B, Wang Z, Jiang C, et al. Enhancement of mammary carcinogenesis in two rodent models by silymarin dietary supplements. Carcinogenesis. 2006;27:1739-1747.

I give Lucy 1 Milk Thistle capsule in her PM meal.

Astragalus Root for Cancer and the immune system

Clinical Summary
Astragalus root works by stimulating several factors of the immune system

Astragalus root is widely used in Traditional Chinese medicine for its tonifying properties. Studies done in China suggest that astragalus, when used with angelica, has reno protective effects (6). In addition, astragalus decreases the proteinuria associated with idiopathic membranous nephropathy (7) and exhibits natriuretic action (8). Astragalus may also suppress airway hyper reactivity associated with allergic asthma in vivo (9). It also increases M-cholinergic receptor density in senile rats (11), which suggests that it may have a role in combating senility. Astragalus extract acts as a nerve-growth promoting factor in vitro and in vivo (17), and alleviates obstructive uropathy in mice in combination Angelica sinensis and standard care (18).
An herbal formula containing astragalus as a major ingredient has been shown to reduce fatigue in athletes (10).

Astragalus extracts inhibit tumor growth (5), delay chemical-induced hepatocarcinogenesis in rats (4), and have antiangiogenic property (19). In vitro, animal, and anecdotal human data show that astragalus reduces immune suppression, a side effect of chemotherapy (1) (2), and may also enhance the effects of platinum-based chemotherapy (3).
Conclusions from a meta-analysis suggest benefits of astragalus-based treatments for hepatocellular cancers, but data need to be evaluated in larger, well designed trials (16).
Improvement in quality of life was reported following use of an injectable form of astragalus with vinorelbine and cisplatin in patients with advanced non-small cell lung cancer (NSCLC) (20). However, it is not known whether orally administered astragalus will exert the same effect.


Purported Uses

    Cardiovascular disease
    Chemotherapy side effects
    Common cold
    Diabetes
    HIV and AIDS
    Immunostimulation
    Microbial infection
    Strength and stamina
    Cancer
    Astragalus root also prevents bone loss and shows osteogenesis ability! Many cancer soften and destroy bone, such as in nasal cancer and bone cancers.


Constituents

    Triperpenoid saponins (cycloastragenol, astragaloside I to VIII, and cyclocanthoside)
    Cycloartane triterpene
    Polysaccharide
    Isoflavonoids
    Amino acids
    (12)


Mechanism of Action

Astragalus works by stimulating several factors of the immune system. The polysaccharides potentiate the immune-mediated antitumor activity of interleukin-2 in vitro (13), improve the responses of lymphocytes from normal subjects and cancer patients, enhance the natural killer (NK) cell activity of normal subjects, and potentiate the activity of monocytes (14), increasing phagocytosis perhaps by regulating tumor necrosis factor (TNF) production (5). The saponins potentiate NK cell activity and restore steroid-inhibited NK cell activity in vitro. They also increase phagocytosis and demonstrate hepatoprotective effects on chemically-induced liver injury in vitro (6) and in vivo (4). Chinese studies suggest that astragalus, when used with angelica, has renal protective effects by mediating gene expression. Astragaloside IV, a saponin constituent, increases tissue-type plasminogen activator (t-PA) synthesis and downregulates the expression of plasminogen activator inhibitor type 1 (PAI-1) (21). Astragalus increases M-cholinergic receptor density in senile rats, suggesting that astragalus may have a role in combating brain senility (11). An herbal formula containing astragalus can reduce fatigue in athletes by increasing uptake and utility of oxygen (10).

Adverse Reactions
Adverse effects have not been reported.

Traditional Chinese medicine Astragalus reverses predominance of Th2 cytokines and their up-stream transcript factors in lung cancer patients.
Oncol Rep. 2003.
Th2 cytokine is predominant in tumor patients and was found to be associated with tumor progression. Reversing of Th2 dominant status is thought to be a promising strategy. Our results demonstrate that traditional Chinese medicine Astragalus might reverse the Th2 predominant status in lung cancer patients, which is a probable alternative therapeutic regime in future.



Literature Summary and Critique

Most of the clinical trials on astragalus were conducted in China using multiple-herbal formulas that contain astragalus as the major component. The selection of herbs is based on Traditional Chinese Medicine.

Wu P, Dugoua JJ, Eyawo O, Mills EJ. Traditional Chinese Medicines in the treatment of hepatocellular cancers: a systematic review and meta-analysis. J Exp Clin Cancer Res. 2009 Aug 12;28:112.
This analysis included 45 randomized controlled trials of oral TCM preparations for hepatocellular cancers and involved 3,236 patients. Survival, tumor response, and performance scores were examined. The authors report that products containing ginseng, astragalus and mylabris had a larger treatment effect (OR 1.34, 95% CI, 1.04-1.71, P = 0.01) than the pooled broad estimate. They observed a similar pattern for  astragalus-based treatments (OR 1.35, 95% CI, 1.001-1.80. P = 0.048).
Astragalus and other TCM products may be effective against hepatocellular cancers. However, the methodology of trials was poor; all the studies were conducted in China and publication bias in favor of only positive reports is likely. The results should be evaluated in well designed trials.

McCulloch M, et al. Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer: Meta-analysis of randomized trials. J clin Oncol 2006;24(3):419-430.
This analysis sought to determine whether Chinese herbal medicine containing Astragalus increases the effectiveness of platinum-based chemotherapy for advanced non-small-cell-lung cancer. Thirty-four randomized studies involving 2,815 patients were analyzed. Results suggest that when used in conjunction with platinum-based chemotherapy, Astragalus-based medicine improved survival, tumor response, performance status, and reduced chemotherapy toxicity when compared with chemotherapy alone.
However, the low quality of the studies analyzed is a drawback and the results are therefore, not conclusive. Well-designed studies are warranted.

Taixiang W, et al. Chinese medical herbs for chemotherapy side effects in colorectal cancer patients (Review). The Cochrane Database Syst Rev 2005; (1):CD004540.
Four clinical trials were included in this review to assess the effectiveness of Astragalus (Huangqi) compounds on the quality of life, side effects of chemotherapy, and on adverse effects in colorectal cancer patients. A decoction of Huangqi compounds was used in combination with chemotherapy in three studies, whereas the fourth study compared Huangqi compounds with two other Chinese herbal formulas. Patients who were given Huangqi compounds experienced a reduction in nausea and vomiting along with a decrease in the rate of leucopenia and an increase in CD3, CD4 and CD8 subsets of T-lymphocytes when compared to those treated with chemotherapy alone in the three studies or with other Chinese formulas in the fourth study.
Use of Chinese herbal medicine along with chemotherapy appears promising for patients with colorectal cancer; however, a major limitation of this review is that it includes only four studies and the studies are of poor quality. Further properly designed trials are needed to confirm these observations.

References

1. 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;25:125-9.
2. Taixiang W, Munro AJ, Guanjian L. Chinese medical herbs for chemotherapy side effects in colorectal cancer patients. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD004540.
3. McCulloch M, See C, Shu XJ, et al. Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer: meta-analysis of randomized trials. J Clin Oncol. 2006 Jan 20;24(3):419-30.
4. Cui R, He J, Wang B, et al. Suppressive effect of Astragalus membranaceus Bunge on chemical hepatocarcinogenesis in rats. Cancer Chemother Pharmacol. 2003 Jan;51(1):75-80.
5. Cho WC, Leung KN. In vitro and in vivo anti-tumor effects of Astragalus membranaceus.Cancer Lett. Jul 8 2007;252(1):43-54.
6. Yu L, Lu Y, Li J, Wang H. Identification of a gene associated with astragalus and angelica's renal protective effects by silver staining mRNA differential display. Chin Med J (Engl) 2002;115:923-7.
7. Ahmed MS, Hou SH, Battaglia MC, et al. Treatment of idiopathic membranous nephropathy with the herb Astragalus membranaceus. Am J Kidney Dis. Dec 2007;50(6):1028-1032.
8. Ai P, Yong G, Dingkun G, et al. Aqueous extract of Astragali Radix induces human natriuresis through enhancement of renal response to atrial natriuretic peptide. J Ethnopharmacol. Mar 28 2008;116(3):413-421.
9. Shen HH, Wang K, Li W, et al. Astragalus Membranaceus prevents airway hyperreactivity in mice related to Th2 response inhibition.J Ethnopharmacol. Mar 5 2008;116(2):363-369.
10. Chen KT, Su CH, Hsin LH, et al. Reducing fatigue of athletes following oral administration of huangqi jianzhong tang. Acta Pharmacol Sin. 2002 Aug;23(8):757-61.
11. Shi R, He L, Hu Y, et al. The regulatory action of radix astragali on M-cholinergic receptor of the brain of senile rats. J Tradit Chin Med 2001;21:232-5.
12. Tang W, et al. Chinese Drugs of Plant Origin. Berlin: Springer-Verlag; 1992.
13. Qun L, Luo Q, Zhang ZY, et al. Effects of astragalus on IL-2/IL-2R system in patients with maintained hemodialysis. Clin Nephrol. 1999 Nov;52(5):333-4.
14. Chu DT, Lepe-Zuniga J, Wong WL, et al. Fractionated extract of Astragalus, a Chinese medicinal herb, potentiates LAK cell cytotoxicity generated by a low dose of recombinant interleukin-2. J Clin Lab Immunol 1988;26:183-7.
15. Upton R. Astragalus root: analytical, quality control and therapeutic monograph. American Herbal Pharmacopoeia. 1999;1:1-25.
16. Wu P, Dugoua JJ, Eyawo O, Mills EJ. Traditional Chinese medicines in the treatment of hepatocellular cancers: a systematic review and meta-analysis. J Exp Clin Cancer Res. 2009 Aug 12;28(1):112.
17. Lu MC, Yao CH, Wang SH, et al. Effect of Astragalus membranaceus in rats on peripheral nerve regeneration: in vitro and in vivo studies. J Trauma. 2010 Feb;68(2):434-40.
18. Wojcikowski K, Wohlmuth H, Johnson DW, Gobe G. Effect of Astragalus membranaceus and Angelica sinensis combined with Enalapril in rats with obstructive uropathy. Phytother Res. 2010 Jun;24(6):875-84.
19. Auyeung KK, Woo PK, Law PC, Ko JK. Astragalus saponins modulate cell invasiveness and angiogenesis in human gastric adenocarcinoma cells. J Ethnopharmacol. 2011 Aug 12.
20. Guo L, Bai SP, Zhao L, Wang XH. Astragalus polysaccharide injection integrated with vinorelbine and cisplatin for patients with advanced non-small cell lung cancer: effects on quality of life and survival. Med Oncol. 2011 Sep 18.
21. Zhang WJ, Wojta J, Binder BR. Regulation of the fibrinolytic potential of cultured human umbilical vein endothelial cells: astragaloside IV downregulates plasminogen activator inhibitor-1 and upregulates tissue-type plasminogen activator expression. J Vasc Res. 1997 Jul-Aug;34(4):273-80.

I give Lucy one Swansonvitamins Astragalus Root capsule in her PM meal.