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Benzopyrones 

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Benzopyrones

Drugs or herbal substances commonly used in Alternative Medicine, falls under the broader class of drugs called flavonoids. Some forms have been found useful in assisting in the treatment of cancers because of their ability to act as inhibitors and suppressants of tumor growths. Other types have been shown to help in the treatment of lymphatic developmental disorders. While these agents have been used for lymphedema in Europe and India there continues to be much debate of their effectiveness. In the United States the FDA has yet to approve their use.

The controversy focuses in two main areas.

First, many of the clincal tests done have been critized for their methodology and lack of control.  This has made the results confusing and/or difficult to verify.  There are also conflicting results in these tests.  For example coumarin was touted as being quite effective in the treatment of arm lymphedema, however in one study done at the Mayo Clinic, it was shown to be actually of little value. 

Secondly is the problem of toxicity.  Coumarin, which was widely used in the 1990's for lymphedema proved to be somewhat toxic with a significant number of people coming down with damaged livers.

Reportedly, this problem is being researched and if that issue can be resolved, then we should see Coumarin reemerge as a treatment option.

Clearly, we need research done by independent scientists in tightly controlled properly done studies.  If these substance can be used and if they can help us, then we must verify it and have them available as an integral part of our management program.

Pat O'Connor

April 27, 2008

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Flavonoids

Broad spectrum of herbal, substances used in Alternative and Complimentary medicine. Flavonoids which are water soluble (versus oil soluble as the carotenes are) have demonstrated antioxidant properties and as such may assist the body in eliminating free radical agents.

These substances were first discovered by Albert Szent-Gyorgi, Ph.D., a Nobel laureate who also discovered vitamin C.

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Benzopyrones in the Treatment of Lymphedema

It has been proposed that benzopyrones would be beneficial for lymphedema patients because of their ability to breakdown the
proteins in the excess lymph fluid and stimulate lymphatic activity.

These drugs bind to accumulated interstitial proteins, inducing macrophage phagocytosis and proteolysis. As a result The resulting protein fragments pass more readily into the venous capillaries and are removed by the vascular system.

Also, as an antioxidant it would help the body cleanse itself of toxins.

The best research available has been due to one individual, J.R. Casley-Smith. He described the benzopyrones, coumarin and troxerutin, for this purpose in 1974. What he has reported is that the process of resolving or having noticeable results from benzopyrones generally takes several months. He also points out that benzopyrones do not remove the cause of protein-rich edemas.

Clearly then, they can only be used as an adjunct to decongestive therapy, compression bandaging and correct garment usage.

Coumarin which is the most widely used benzopyrone has also been implicated in liver toxicity.

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Benzo-pyrones for reducing and controlling lymphedema of the limbs

Cochrane Database Syst Rev. 2004

Badger C, Preston N, Seers K, Mortimer P.

BACKGROUND: Lymphedema is the accumulation of excess fluid in the body caused by obstruction of the lymphatic drainage mechanisms. It can be caused by a number of factors, including congenital predisposition, parasitic infection or surgery. Lymphoedema is chronic and progressive and affects a significant proportion of the population. The standard treatment regimes include compression hosiery, skin care and exercise. The use of drugs in treatment, particularly benzo-pyrones, has gained favour over the last ten years. Benzo-pyrones, originally developed for use in vascular medicine, are prescribed to reduce vascular permeability and thus the amount of fluid forming in the subcutaneous tissues. Advocates for this treatment method believe that, as a result of reducing filtration, the drugs have some beneficial effect on pain and discomfort in the swollen areas. Proponents also claim that these drugs increase macrophage activity, encouraging the lysis of protein, which in turn reduces the formation of fibrotic tissue in the lymphoedematous limb. 

OBJECTIVES: To assess the effectiveness of benzo-pyrones compared to placebo or to different benzo-pyrones in reducing limb volume, pain and discomfort in lymphoedematous limbs. To assess the effect of benzo-pyrones on the quality of affected tissues and on the patient's quality of life and, finally, to establish the incidence of adverse effects 

SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group register (September 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4,2003), MEDLINE, EMBASE, CINAHL, UnCover, PASCAL, SIGLE, reference lists produced by The British Lymphology Society, the National Research Register (NRR) and The International Society of Lymphology congress proceedings. 

SELECTION CRITERIA: Types of studies considered for review were randomised controlled trials testing Paroven, coumarin, Venastat, Cyclo 3 Fort or Daflon versus placebo (with both groups having or not having standard physical treatment 

DATA COLLECTION AND ANALYSIS: Eligibility for inclusion was confirmed by two blinded reviewers who screened the papers independently using a checklist of criteria relating to the randomisation and blinding of the trial. Both reviewers extracted data from the eligible studies using a data extraction form. 

MAIN RESULTS: Overall, 15 trials were included that evaluated the role of benzo-pyrones. Three trials of oxerutin were found. Each tested the drug over 6 months using the same dose of drug against placebo. Two were crossover trials and one a parallel group trial with a total number of 127 participants and data available for only 81 of them. There were insufficient data provided in any of the trials to calculate the per cent reduction or increase in baseline excess limb volume. Standard deviations or confidence intervals and the numbers in the groups at the different stages of the trial were missing for all the data in two of the reports and for much of the data in the third, making any attempt at meta-analysis impossible.

One trial testing Cyclo 3 Fort (approved name) over 3 months was found and involved 57 patients but provided insufficient data to allow a proper analysis of its findings. A single trial of Daflon (approved name) was found, lasting 6 months and involving 104 participants; once again there was insufficient information provided in the report to reach a conclusion about the effectiveness of the drug. Three trials of coumarin combined with troxerutin were found and tested two different doses of the drug against each other with no placebo, however, numbers of participants in the trial groups and baseline data were not provided. Eight trials of coumarin were identified. Two of the reports were confirmed as reporting the same trial and a further trial potentially also referred to the same trial but this was unconfirmed. A further two papers appeared to refer to the same trial but this was not confirmed. Three trials involved the same researcher. 

Five studies were conducted in India or China and they added anti-filarial dia or China and they added anti-filarial drugs to the interventions tested. The numbers of participants withdrawn and the numbers included in the analyses in all these trials were not extractable; the reporting of outcome measures in most of the trials was not clear. Loprinzi's 1999 trial in the USA reported the conduct of the trial and its findings with more detail, however, its conclusions were very much at odds with the findings of the other trials, finding that no difference was observed between those on the active preparation (coumarin) and placebo in any of the outcomes under investigation. This trial also reported a case of hepato-toxicity in a patient receiving the active preparation. 

REVIEWERS' CONCLUSIONS: Meta-analysis was not performed due to the poor quality of the trials. It is not possible to draw conclusions about the effectiveness of Benzopyrones in reducing limb volume, pain, or discomfort in lymphoedematous limbs from these trials.

Cochrane Library

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External Links: 

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Pharmaceutical Options in the Treatment of Lymphedema

http://www.lymphedemablog.com/tag/benzopyrones/

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The Benzo-pyrone Drugs in the Treatment of Lymphoedema (and other High-Protein Oedemas)

J.R. Casley-Smith & Judith R. Casley-Smith (L.A.A., 94 Cambridge Tce., Malvern, SA 5061, Australia)

http://www.lymphoedema.org.au/index.htm

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Comparative Study of the Clinical Efficacy of Two Different Coumarin Dosages in the Management of Arm Lymphedema After Treatment for Breast Cancer

http://www.u.arizona.edu/~witte/contents/1999.1.burgos.pdf

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Lymphovenous Canada: Liver toxicity raises doubts about coumarin

http://www.lymphovenous-canada.ca/benzo.htm

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Lack of effect of coumarin in women with lymphedema after treatment for breast cancer.

Loprinzi CL, Kugler JW, Sloan JA, Rooke TW, Quella SK, Novotny P, Mowat RB, Michalak JC, Stella PJ, Levitt R, Tschetter LK, Windschitl H.

Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. loprinzi.charles@mayo.edu

Abstract

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9929524&dopt=Abstract

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Contribution of a combination of alpha and beta benzopyrones, flavonoids and natural terpenes in the treatment of lymphedema of the lower limbs at the 2d stage of the surgical classification

Vettorello G, Cerreta G, Derwish A, Cataldi A, Schettino A, Occhionorelli S, Donini I.

Istituto di Clinica Chirurgica, Universita degli Studi, Ferrara.

Abstract

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8999369&dopt=Abstract

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Chinese Herbs for the Treatment of Lymphedema

Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon

*scroll down as this site has an excellant section on benzopyrones*

http://www.itmonline.org/arts/lymphedema.htm

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Current Status of Selenium and Other Treatments for Secondary Lymphedema

Frank Bruns, MD, Oliver Micke, MD, and Michael Bremer, MD

Department of Radiotherapy, Hannover Medical School, Hannover, Germany, and Department of Radiotherapy, Münster University Hospital, Münster, Germany

http://www.ncbi.nlm.nih.gov/pubmed/15352655

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Why Nutrients Called Flavonoids Are Good For You

http://www.drpasswater.com/nutrition_library/flavonoids.html

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Natural product biosynthesis inspired concise and stereoselective synthesis of benzopyrones and related scaffolds.

http://pubs.acs.org/doi/abs/10.1021/ol200389p

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Anti-inflammatory properties of dietary flavonoids.

http://www.ncbi.nlm.nih.gov/pubmed/17612370

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Index of articles for  Lymphedema Treatment :

Lymphedema Treatment 

http://www.lymphedemapeople.com/wiki/doku.php?id=treatment

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Acupuncture Treatment

 http://www.lymphedemapeople.com/thesite/lymphedema_acupuncture_treatment.htm

Aqua Therapy for Postsurgical Breast Cancer Arm Lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=aqua_therapy_for_postsurgical_breast_cancer_arm_lymphedema

Aqua Therapy in Managing Lower Extremity Lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=aqua_therapy_in_managing_lower_extremity_lymphedema

Artificial Lymph Nodes

http://www.lymphedemapeople.com/wiki/doku.php?id=artificial_lymph_nodes

Artificial Lymphatic System

http://www.lymphedemapeople.com/wiki/doku.php?id=artificial_lymphatic_system

Auricular Therapy

http://www.lymphedemapeople.com/wiki/doku.php?id=auricular_therapy

Ball Massage technique

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=377

Compression Bandages for Lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=compression_bandages_for_lymphedema

Benzopyrones Treatment

http://www.lymphedemapeople.com/thesite/lymphedema_benzopyrones_treatmen.htm

Chi Machine

http://www.lymphedemapeople.com/thesite/lymphedema_and_the_chi_machine.htm

Choosing a Rehabilitation Provider or Physical Therapist

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=1120

Complex Decongestive Therapy

http://www.lymphedemapeople.com/wiki/doku.php?id=manual_lymphatic_drainage_mld_complex_decongestive_therapy_cd

Complications of Lymphedema Debulking Surgery

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=200

Compression Garments Stockings for Lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=compression_garments_stockings_for_lymphedema

Compression Pumps for Lymphedema Treatment

http://www.lymphedemapeople.com/wiki/doku.php?id=compression_pumps_for_lymphedema_treatment

Coumarin powder/ointment

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=768

Craniosacral Therapy

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=432

Daflon 500 and Secondary Lymphedema

Deep Oscillation Therapy

http://www.lymphedemapeople.com/wiki/doku.php?id=deep_oscillation_therapy

Diaphragmatic Breathing

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=113

Diuretics are not for lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=diuretics_are_not_for_lymphedema

Endermologie Therapy

http://www.lymphedemapeople.com/thesite/lymphedema_and_endermologie_therapy.htm

Essential Oils

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=435

Elastin Ampules

Farrow Wrap

http://www.lymphedemapeople.com/wiki/doku.php?id=farrow_wrap

Flexitouch Device - Initial Observations

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=155

Flexitouch Device for Arm Lymphedema

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=273

Homeopathy

http://www.lymphedemapeople.com/thesite/lymphedema_and_homeopathy.htm

How to Choose a Lymphedema Therapist

http://www.lymphedemapeople.com/wiki/doku.php?id=how_to_choose_a_lymphedema_therapist

How to be Safe with Complementary and Alternative Medicine

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=66

Infrared Therapy for Lymphedema

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=429

Kinesio Taping (R)

http://www.lymphedemapeople.com/thesite/lymphedema_and_kinesio_taping.htm

Kinesiology Therapy

http://www.lymphedemapeople.com/thesite/lymphedema_and_kinesiology_therapy.htm

Laser Treatment

http://www.lymphedemapeople.com/thesite/lymphedema_laser_treatment.htm

Laser Treatment - Sara's Experience

 http://www.lymphedemapeople.com/thesite/lymphedema_laser_treatment_saras_experience.htm

Light Beam Generator Therapy

http://www.lymphedemapeople.com/thesite/lymphedema_and_light_beam_generator_therapy.htm

Liposuction Treatment

 http://www.lymphedemapeople.com/thesite/lymphedema_liposuction_treatment.htm

Low Level Laser

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=114

Lymph Node Transplant

http://www.lymphedemapeople.com/wiki/doku.php?id=lymph_node_transplant

Lymphatic venous anastomoses

Lymphedema Treatment Programs Canada

http://www.lymphedemapeople.com/thesite/lymphedema_treatment_programs_canada.htm

Lymphedema Sleeves

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_sleeves

Lymphedema Surgeries

http://www.lymphedemapeople.com/thesite/lymphedema_surgeries.htm

Lymphedema Treatments are Poorly Utilized

http://www.lymphedemapeople.com/thesite/lymphedema_treatments_are_poorly_utilized.htm

Lymphobiology

http://www.lymphedemapeople.com/thesite/lymphedema_and_lymphobiology.htm

Lymphocyte injection therapy

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=632

Lymphomyosot

Magnetic Therapy

http://www.lymphedemapeople.com/thesite/lymphedema_and_magnetic_therapy.htm

Manual Lymphatic Drainage

http://www.lymphedemapeople.com/wiki/doku.php?id=manual_lymphatic_drainage_mld_complex_decongestive_therapy_cdt

Mesotherapy

http://www.lymphedemapeople.com/wiki/doku.php?id=mesotherapy

Microsurgeries

http://www.lymphedemapeople.com/thesite/lymphedema_and_microsurgery.htm

Naturopathy: A Critical Appraisal

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=202

Patient self-massage for breast cancer-related lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=patient_self-massage_for_breast_cancer_related_lymphedema

Reflexology Therapy

http://www.lymphedemapeople.com/thesite/lymphedema_and_reflexology_therapy.htm

Self Massage Therapy – Self MLD

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=227

Short Stretch Bandages

http://www.lymphedemapeople.com/wiki/doku.php?id=short_stretch_bandages_for_lymphedema

Surgeries

http://www.lymphedemapeople.com/thesite/lymphedema_surgeries.htm

Wholistic Treatment

http://www.lymphedemapeople.com/thesite/lymphedema_wholistic_treatment.htm

Treatment Information for Lymphedema Forum

http://www.lymphedemapeople.com/phpBB2/viewforum.php?f=8

Why Compression Pumps cause Complications with Lymphedema

http://www.lymphedemapeople.com/phpBB2/viewtopic.php?t=327

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Join us as we work for lymphedema patients everywehere:

Advocates for Lymphedema

Dedicated to be an advocacy group for lymphedema patients. Working towards education, legal reform, changing insurance practices, promoting research, reaching for a cure.

http://health.groups.yahoo.com/group/AdvocatesforLymphedema/

Subscribe: AdvocatesforLymphedema-subscribe@yahoogroups.com

Pat O'Connor

Lymphedema People / Advocates for Lymphedema

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For information about Lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema\

For Information about Lymphedema Complications

http://www.lymphedemapeople.com/wiki/doku.php?id=complications_of_lymphedema

For Lymphedema Personal Stories

http://www.lymphedemapeople.com/phpBB2/viewforum.php?f=3

For information about How to Treat a Lymphedema Wound

http://www.lymphedemapeople.com/wiki/doku.php?id=how_to_treat_a_lymphedema_wound

For information about Lymphedema Treatment 

http://www.lymphedemapeople.com/wiki/doku.php?id=treatment

For information about Exercises for Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=exercises_for_lymphedema

For information on Infections Associated with Lymphedema

http://www.lymphedemapeople.com/wiki/doku.php?id=infections_associated_with_lymphedema

For information on Lymphedema in Children

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_in_children

Lymphedema Glossary

http://www.lymphedemapeople.com/wiki/doku.php?id=glossary:listing

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Lymphedema People - Support Groups

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Children with Lymphedema

The time has come for families, parents, caregivers to have a support group of their own. Support group for parents, families and caregivers of chilren with lymphedema. Sharing information on coping, diagnosis, treatment and prognosis. Sponsored by Lymphedema People.

http://health.groups.yahoo.com/group/childrenwithlymphedema/

Subscribe: childrenwithlymphedema-subscribe@yahoogroups.com

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Lipedema Lipodema Lipoedema

No matter how you spell it, this is another very little understood and totally frustrating conditions out there. This will be a support group for those suffering with lipedema/lipodema. A place for information, sharing experiences, exploring treatment options and coping.

Come join, be a part of the family!

http://health.groups.yahoo.com/group/lipedema_lipodema_lipoedema/?yguid=209645515

Subscribe: lipedema_lipodema_lipoedema-subscribe@yahoogroups.com

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MEN WITH LYMPHEDEMA

If you are a man with lymphedema; a man with a loved one with lymphedema who you are trying to help and understand come join us and discover what it is to be the master instead of the sufferer of lymphedema.

http://health.groups.yahoo.com/group/menwithlymphedema/

Subscribe: menwithlymphedema-subscribe@yahoogroups.com

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All About Lymphangiectasia

Support group for parents, patients, children who suffer from all forms of lymphangiectasia. This condition is caused by dilation of the lymphatics. It can affect the intestinal tract, lungs and other critical body areas.

http://health.groups.yahoo.com/group/allaboutlymphangiectasia/

Subscribe: allaboutlymphangiectasia-subscribe@yahoogroups.com

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Lymphatic Disorders Support Group @ Yahoo Groups

While we have a number of support groups for lymphedema... there is nothing out there for other lymphatic disorders. Because we have one of the most comprehensive information sites on all lymphatic disorders, I thought perhaps, it is time that one be offered.

DISCRIPTION

Information and support for rare and unusual disorders affecting the lymph system. Includes lymphangiomas, lymphatic malformations, telangiectasia, hennekam's syndrome, distichiasis, Figueroa
syndrome, ptosis syndrome, plus many more. Extensive database of information available through sister site Lymphedema People.

http://health.groups.yahoo.com/group/lymphaticdisorders/

Subscribe: lymphaticdisorders-subscribe@yahoogroups.com

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Lymphedema People New Wiki Pages

Have you seen our new “Wiki” pages yet?  Listed below are just a sample of the more than 140 pages now listed in our Wiki section. We are also working on hundred more.  Come and take a stroll! 

Lymphedema Glossary 

http://www.lymphedemapeople.com/wiki/doku.php?id=glossary:listing 

Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema 

Arm Lymphedema  

http://www.lymphedemapeople.com/wiki/doku.php?id=arm_lymphedema 

Leg Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=leg_lymphedema 

Acute Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=acute_lymphedema 

The Lymphedema Diet 

http://www.lymphedemapeople.com/wiki/doku.php?id=the_lymphedema_diet 

Exercises for Lymphedema  

http://www.lymphedemapeople.com/wiki/doku.php?id=exercises_for_lymphedema 

Diuretics are not for Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=diuretics_are_not_for_lymphedema 

Lymphedema People Online Support Groups 

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_people_online_support_groups 

Lipedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=lipedema 

Treatment 

http://www.lymphedemapeople.com/wiki/doku.php?id=treatment 

Lymphedema and Pain Management 

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_and_pain_management 

Manual Lymphatic Drainage (MLD) and Complex Decongestive Therapy (CDT)

http://www.lymphedemapeople.com/wiki/doku.php?id=manual_lymphatic_drainage_mld_complex_decongestive_therapy_cdt 

Infections Associated with Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=infections_associated_with_lymphedema 

How to Treat a Lymphedema Wound 

http://www.lymphedemapeople.com/wiki/doku.php?id=how_to_treat_a_lymphedema_wound 

Fungal Infections Associated with Lymphedema 

http://www.lymphedemapeople.com/wiki/doku.php?id=fungal_infections_associated_with_lymphedema 

Lymphedema in Children 

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_in_children 

Lymphoscintigraphy 

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphoscintigraphy 

Magnetic Resonance Imaging 

http://www.lymphedemapeople.com/wiki/doku.php?id=magnetic_resonance_imaging 

Extraperitoneal para-aortic lymph node dissection (EPLND) 

http://www.lymphedemapeople.com/wiki/doku.php?id=extraperitoneal_para-aortic_lymph_node_dissection_eplnd 

Axillary node biopsy 

http://www.lymphedemapeople.com/wiki/doku.php?id=axillary_node_biopsy

Sentinel Node Biopsy 

http://www.lymphedemapeople.com/wiki/doku.php?id=sentinel_node_biopsy

 Small Needle Biopsy - Fine Needle Aspiration 

http://www.lymphedemapeople.com/wiki/doku.php?id=small_needle_biopsy 

Magnetic Resonance Imaging 

http://www.lymphedemapeople.com/wiki/doku.php?id=magnetic_resonance_imaging 

Lymphedema Gene FOXC2

 http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_foxc2

 Lymphedema Gene VEGFC

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_vegfc

 Lymphedema Gene SOX18

 http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_sox18

 Lymphedema and Pregnancy

http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_and_pregnancy

Home page: Lymphedema People

http://www.lymphedemapeople.com

Page Updated: Jan. 15, 2012