Medicines and Selenium Supplements for Lymphedema

Medicines and Selenium Supplements for Lymphedema

This blog will focus on prescription medicine and selenium supplements for lymphedema.  I do have another blog on Herbs for Lymphedema. But before you jump to that, be sure to read this information about selenium as it has more research and more promising results than herbal products for lymphedema.

I’m doing this to help you decide if a medication or selenium supplement for lymphedema is right for you. But, this blog does not substitute for medical advice and you should consult your medical care team before taking any supplements. Also, to be clear, I have no financial interest in any lymphatic drainage supplement company, nor do I sell any lymphatic drainage supplements.

As I review the research on supplements for lymphedema patients, I’m limiting my reporting to human studies only. I am not reporting on any animal studies. Also, I am reporting on studies on lymphedema only, not on chronic venous insufficiency.

You can read this post from top to bottom, or navigate using this Table of Contents

Medicines for Lymphedema

A few prescription medicines have been studied for use against lymphedema, including corticosteroids, diuretics, cyclophosphamide, pamidronate, terbutaline sulfate and theophylline. This is my review of the research for medicines and lymphedema.

one blister pack of white pills and coloured pills on top
Prescription medicines and supplements have been tested with lymphedema. This blog will review the results. Image by Matvevna from Pixabay.

Corticosteroids for Lymphedema

Corticosteroids are drugs that resemble our body’s hormones that are produced by the adrenal gland and include cortisone, prednisone and dexamethasone. They are often prescribed to treat inflammation are given for as short a time as possible and weaned off of gradually. People often just call them ‘steroids’, but are not the same as the drugs used in athletic doping.

While I could not find any trials, I was able to find, this summary statement from a couple of papers. “Lymphedema is an inflammatory condition, corticosteroids have shown only short-term benefit but unfortunate have left individuals susceptible to infection (Micke, 2003 and Bruns, 2004).

Diuretics for Lymphedema

Diuretics are drugs that make the body lose more fluid through the kidneys. Essentially, they make you pee more and are often called ‘water pills’ for this reason.

These are very valuable for individuals with congestive heart failure, high blood pressure or ascites. Sometimes individuals with these conditions can have edema in the ankles and lower legs. This edema can look similar to lymphedema, but while diuretics can help edema due to high blood pressure or congestive heart failure, they are not recommended for lymphedema.

This is because lymphedema fluid is high in protein and when the water is removed from the lymphedema after taking diuretics, the lymph fluid becomes more concentrated with protein. This encourages the area to develop more fibrosis (hardening) (Micke, 2003).

A more recent publication described it this way “diuretics, although widely prescribed for this chronic, edematous condition, are rarely useful and may in fact be deleterious” (Cooke, 2012).

box of furosemide tablets
Diuretics, like furosemide are not recommended for lymphedema. Image from Dailymed.nlm.nih.giv

 

Cyclophosphamide for Lymphedema

This study was done in the 1960’s in Liverpool, England. Four people with arm lymphedema and functioning deep lymphatics had 150-200 mg of cyclophosphamide in 4-5 ml of saline injected slowly over about 1 hour into the wrist (Kitchen, 1971).

Cyclophosphamide is a form of chemotherapy used to treat lymphoma (cancer or the lymph nodes), multiple myeloma, leukemia, ovarian, and breast cancer among others.

Patient 1 experienced almost immediate pain relief and softening of the arm within one day. The arm circumference reduced by one inch in the mid-bicep area. Eight months later, the arm remained soft and edema free.

Patient 2 had an increase in swelling and pain of the arm three days after the cyclophosphamide. An antibiotic was given and the pain and swelling was reduced and continued to reduce until four months later the mid-bicep was down 1 ½  inches, and was softer. But the hand continued to feel cold.

Patient 3 had a reduction in arm swelling one day after cyclophosphamide. Two weeks later the arm was still softer, but had not gone down in size.

Patient 4 had an arm circumference of 25 inches before cyclophosphamide and four months after cyclophosphamide, had reduced only one inch.

Despite the authors conclusions that intra-lymphatic cyclophosphamide is worth considering if symptoms are severe and the patient’s general condition is otherwise good, this technique seems to have been abandoned as I am not aware of any hospital that is treating patients in this way.

No other research has cited this paper except a 2019 review article that was reviewing the use of pharmacotherapy in lymphedema (Forte, 2019). So, it seems this technique never got any traction for whatever reason.

Clearly a lot has changed in lymphedema care since the 1960’s and new trials would have to be done for this to be considered.

Ketoprofen for Lymphedema

Ketoprofen is a non-steroidal anti-inflammatory, otherwise known as an NSAID. Ketoprofen is a pharmaceutical drug, but it is available both over-the-counter and by prescription. It is used to relieve pain from various sources including arthritis or gout.

According to healthlinkBC, it works by blocking your body’s production of certain natural substances that cause inflammation (healthlinkBC, 2018). Unfortunately, there are potential side-effects including stomach bleeding, high blood pressure and various GI effects.

There are two studies by the same researchers which I will describe for you.

Ketoprofen and Lymphedema Study #1

In this study from Stanford University, 21 people with either primary or secondary lymphedema were given 75 mg of ketoprofen three times per day (total 225 mg) for four months (Rockson, 2018). This was an open-label study, which means, the subjects knew that they were receiving ketoprofen.

Results

The patients experienced a significant reduction in skin thickness, which is a hallmark of lymphedema and previously has been shown to correlate with the severity of the lymphedema. But, no difference in volume of lymphedema.

Ketoprofen and Lymphedema Study #2

This was done by the same research team at Stanford University. This time 30 individuals completed the study (Rockson, 2018).

Because of the reported side-effects of ketoprofen, anyone with cardiovascular disease, high blood pressure or a smoker were not allowed to participate.

This time, it was a placebo-controlled trial. This means that the participants received either a placebo or ketoprofen, but didn’t know which one they were taking. The dosage was 75 mg per day, three times a day.

Results

This trial also showed a significant reduction in skin thickness. In addition, blood levels of inflammation were reduced, which was expected, as ketoprofen is an anti-inflammatory, this is significant as one type of immune cells, called macrophages can produces inflammatory messengers called leukotriene B4 (LTB) which have the potential to injure the skin cells.

Bottom Line for Ketoprofen and Lymphedema

While it was certainly positive that the skin thickness reduced, it was disappointing to see that the limb volume did not. The researchers discuss that, limb volume in lymphedema is mainly due to an increase in the size of the fat cells within the lymphedema limb and that the fat cells may need more than four months in order to respond.

However, this may prove problematic as ketoprofen and other NSAIDS come with a warning that users may experience cardiovascular toxicity. While there were no serious side-effects and no cellulitis during the four month trial, we can’t assume that longer term usage will also be side-effect free.

The use of ketoprofen for lymphedema would require a serious risk-benefit discussion with your physician. Certainly if you have risk factors for heart disease then the potential benefits of reduced skin thickness and inflammation may not be worth the potential risks of cardiotoxicity. Especially when an anti-inflammatory diet has also shown to be able to reduce blood levels of inflammation and comes without risks.

Pamidronate for Lymphedema

This trial was conducted in Iran with 12 patients that had lymphedema that was unresponsive to manual lymphatic drainage, lymphatic pump or compression garments.

The patients received 60 mg of disodium pamidronate concentrated solution (15 mg/ml) via IV infusion diluted in 500 ml of dextrose or normal saline infused over six hours (Beigi, 2011)

Pamidronate is used to treat high levels of calcium in the blood that may be caused by certain types of cancer and used to treat bone damage in multiple myeloma (MedlinePlus, 2015).

If their serum calcium levels were normal or low, then also received a calcium supplement before the infusion. No other medications were given.

After the pamidronate infusion, they were asked to continue their usual treatments of elevation and compression.

Liquid dripping through the chamber on IV tubing
Unlike the other medicines reviewed above which were oral pills, this one was an IV infusion. Photo by Hiroshi Tsubono on Unsplash

Results

The lymphedema volume decreased progressively with each month’s infusion. The patients reported improvements in the use of their limb. There were no side-effects except for deep muscle pain that subsided after the infusion.

The authors concluded that Pamidronate had incredible effects on lymphedema including improved patient comfort, increased use of the limb and reduced lymphedema volume. They suggest randomized, double blind studies with a placebo to confirm these findings.

Terbutaline Sulfate, Theophylline and Lymphedema

Terbutaline and theophylline are prescribed to treat wheezing, shortness of breath and chest tightness caused by asthma, emphysema and chronic bronchitis (Medline Plus, 2017 and 2019).

There was a single case report published by Doctors Moore and Ballas from the University of Iowa Hospitals, one of the few North American pharmatherapy and lymphedema publications (the other being the Rockson trial from Stanford).

In this case study, a 53 year old woman with angioedema, capillary leak syndrome and non-pitting lymphedema in all four limbs plus her abdomen. She was given terbutaline sulfate 5 mg, five times a day plus theophylline 200 mg, twice a day (Moore, 2009).

One week after the treatment there was an improvement in her lymphedema. Her weight decreased by 14 kg (31 lbs) after 10 months of treatment (0.73 lbs/week).

The two physicians who published the study surmised that the medications likely increased the levels of cyclic adenosine monophosphate (cAMP) which is known to decrease endothelial cell permeability. They concluded that “we propose the use of this therapeutic modality for patients with idiopathic lymphedema”.

Say what? I’ve read a lot of research in my time…the typical conclusions are “more study is needed with larger randomized controlled trials”. I’m surprised by this conclusion after only one case study of a woman who seems to have a rather unique presentation of angioedema, capillary leak syndrome and non-pitting lymphedema in all four limbs plus her abdomen.

But, I’m guessing not to many clinicians have followed this advice, as a dozen years later, this is not standard therapy for lymphedema.

Bottom Line for Medicines for Lymphedema

Based only on the research here and no clinical experience of my own with any of these medicines for lymphedema, it seems that cyclophosphamide, Pamidronate and possibly the combination of Terbutaline Sulfate and Theophylline deserve a second look.

It seems research is lacking in pharmaceutical approaches to lymphedema, but I am hoping that this could be re-energized and that researchers are willing to look at this and people with lymphedema are willing to participate in trials.  Until then, it would be difficult for a physician to prescribe any of these with great confidence.

Selenium for Lymphedema 

Selenium is an essential mineral found naturally in many foods. Selenium exists in two forms; inorganic and organic (this refers to the chemistry and not organic farming). Food sources include Brazil nuts, seafoods and organ meats (NIH, 2021)

Of all the nutritional supplements for lymphedema, selenium has the greatest number of studies. I’ll walk you through them here.

Two original papers were published in German in 1996 and 1997 but are summarized in English in a review paper published in 2000. I’ll describe it for you.

A brand of selenium called Selenase® was used in the research. This is a sterile solution of sodium selenite in drinking ampoules with 200 micrograms of selenium in 2 ml of solution.

The reason selenium is being investigated is that selenium is an anti-oxidant with strong anti-inflammatory properties. This can work on the microcirculation in the area of lymphedema, which is characterized by inflammation (Kasseroller, 2000).

Brazil nuts on cutting board beside bowl
Selenium is an essential trace mineral that is found in our food. Brazil nuts, pictured above provides you with your daily requirement for selenium. Other food sources include seafood and organ meats. Image by Geraldine Dukes from Pixabay.

Selenium for Lymphedema Study #1 (Kasseroller, 2000)

This study involved 179 women who had had a mastectomy for breast cancer and developed lymphedema as a result. It had been 12 months since their last decongestive therapy session for their stage I or II lymphedema.

After enrolling in the study, the participants were advised to do self-care for their lymphedema including hygiene and skin care, were given identical lotion and wrappings and were advised to follow a low fat and low salt diet (more on lymphedema diet).

They all received decongestive therapy twice a day including compression bandaging and exercise for three weeks. They were blinded and randomized to either received placebo or Selenase® as follows:

  • 1000 micrograms per day (333 micrograms of  three times a day) before meals for week one
  • 300 micrograms per day for weeks two and three
  • 100 micrograms for the remaining three months if they weighed less than 70 kg (154 lbs.)
    • or 200 micrograms if they weighed more than 70 kg (154 lbs.)

The participants in the placebo group following the same regimen in terms of volume of solution, but there’s was a saline placebo.

Results

After three weeks of Selenase®, the blood selenium levels did increase from 69 (+/- 8) to 112 (+/- 24) micrograms/litre. While the selenium blood levels did not change in the placebo group, which confirms what was expected.

The lymphedema volume reduced as follows;

  • – 524 ml in the Selenase® group
  • – 420 ml in the placebo group

The average weight loss in the two groups were as follows;

  • – 1.5 kg (3.3 lbs.) in the Selenase® group
  • – 1.0 kg (2.2 lbs.) in the placebo group

In addition, compared to placebo, the Selenase® takers had greater improvements in;

  • Peeing during the night
  • Vision
  • Dry skin
  • Heat sensitivity in the lymphedema arm
  • Softer skin in the lymphedema arm
  • Mood
  • Skin fold index
  • Skin fold thickness
  • Incidence of erysipelas (bacterial infection in the skin)

When the Selenase® takers compared their current reduction in limb volume to their previous compression bandaging. There were mixed results, two had 14% less reduction but six participants had better results with the compression bandaging while on Selenase® with a 33% improvement in lymphedema reduction.

Bottom Line for Selenase® Study #1

The Selenase®  was well tolerated in the study with no reported side-effects. It should be noted that vitamin C supplements should not be taking with Selenase® as it can reduce the effectiveness.

In the discussion section of the paper, it was noted that Selenase® works best for those with lymphedema of two years duration or less as advanced lymphedema can become fibrotic and calcified and Selenase® is less effective in these individuals. But it did still protect against erysipelas (skin infections) and help to soften the limb.

It should be noted that the Selenase® was given along with compression bandaging. It is thought that one of the mechanisms of action of the selenium is that it can help to unclog lymphatic capillaries and provide a spontaneous reduction in lymph volume but also to improve the efficacy of decongestive bandaging.

3 boxes of Selenase and vials of clear liquid
The version of sodium selenate used in the trials is Selenase, made by the German company Biosyn

Selenium for Lymphedema Study #2 (Micke, 2002)

This study was done in Germany with 48 patients who had received radiation for cancer treatment. Twelve had lymphedema in the arm and 36 had head and neck lymphedema.

The trial consisted of sodium selenite, brand name Selenase® by mouth once a day for four to six weeks. The dosage was dependent on a persons size, but on average was 500 micrograms per day (dosage was 350 micrograms per metre2 body surface area). The Selenase® was started between 2 and 16 months after radiation finished.

Results

One of the measures used in the study was a visual analog scale. Simply put, the physician and the patient rates their estimation of their condition by a 0-10 scale. A higher number means a lower quality of life.

Before the study the average visual analog scale rating of all patients was 7.3 (+/-1.9). Following selenium treatment it was 3.0 (+/-2.6). This means, there was an improvement in the estimation of health.

A more quantitative finding was actually measuring the airway opening using a microlaryngoscope. Thirteen of 20 patients who had this scope showed an improvement in the airway edema. No side effects were reported by any of the participants.

In addition, most patients who have edema in the laryngeal area will require a tracheostomy. But in this study, at least during the four months while they were on the Selenase®, only 5 out of 20 needed a temporary tracheostomy and 2 out of 20 needed a permanent tracheostomy.

Conclusions on Study #2

The authors of this study concluded that “selenium supplementation resulted in a reduction in lymphedema”, however without a control group they are stating this based on the fact that most people with lymphedema get worse over time and this group did not. They report no side-effects of the selenium supplementation.

I did enjoy the authors discussion as to the mechanism of action, specifically;

  • Lymphostasis creates more reactive oxygen species (“free radicals”) and selenium is a strong anti-oxidant
  • Many people diagnosed with cancer of the head and neck region usually present with low blood levels of selenium (and zinc) and decreased anti-oxidant enzymes
  • Selenium “unclogs’ lymph capillaries invaded by leukocytes by preventing sticky adhesion molecules from attaching to the lymphatic capillaries
  • Selenium may stimulate macrophages (‘big eater’ immune cells) to break down (or eat up) the excess tissue protein in the lymph fluid

Selenium for Lymphedema Study #3 (Bruns, 2004)

Like the previous study, this one was also done in Germany and used the sodium selenite brand Selenase®. This study included 36 patients with cancer in the head or neck region. There was no placebo group in this study, meaning that all 36 people received the selenium supplement.

The dosage used was about  500 micrograms per day (calculated based on the patient’s body size: 350 micrograms/m2 body surface area by mouth). This was given for 4-6 weeks.

Results

A scoring system was used to grade the severity of the lymphedema before and after treatment. Ten out of sixteen patients showed improvements in their lymphedema using the Földi and Földi scoring system and twelve out of sixteen improved using the Miller scoring system.

Patients also completed quality of life questionnaires before and after treatment. These improved significantly.

This paper also appears to report on the same 20 patients had endolaryngeal swelling as the Micke, 2002 study above, so I won’t repeat those findings.

There were no side-effects reported from the selenium supplementation and it was well tolerated.

Selenium for Lymphedema Study #4 (Zimmerman, 2005)

Similar to study #3 described above, this study also took place in Germany with individuals following surgery for squamous cell oral cancer. Twenty people were enrolled in a study to give 1000 micrograms of sodium selenite either by IV or by mouth daily for three weeks starting prior to their oral surgery or placebo. This study did not specify any particular brand of supplement used.

This was a placebo-controlled, double-blinded and randomized trial – in other words, the best type of research design.

Of the 18 men and 2 women, half received the sodium selenite and the other half a placebo starting on the day of their surgery for a neck dissection and continuing for three weeks.

Lymphedema was measured in the tragus, nostrils, corner of the mouth and tip of the chin. All measurements were made by the same person to avoid variation in technique.

Results

These authors were looking at several outcomes, including lymphedema measurements and blood levels of selenium and anti-oxidant glutathione peroxidase.

Patients who received selenium had a more rapid reduction in lymphedema at all of the time parameters; one week post surgery, two weeks post surgery.

The higher the blood levels of selenium and glutathione peroxidase, the lower the severity of lymphedema.

These authors report that 1000 micrograms per day should not be expected to produce any side-effects and that it is of particular benefit to patients who have undergone extensive lymph node removal.

I did enjoy reading the description of lymphedema fibrosis in this paper, which I will summarize here for you; When there is an increase in lymphatic fluid in the interstitium (the extracellular spaces outside of the blood), there is an increase in protein in this space also. The lymph vessels dilate as a result of the increased work load and the lymph capillaries become leakier.

The increased protein concentrations activate fibroblasts – cells whose job is it to create fibrosis. This also attracts immune cells like neutrophilic granulocytes that create reactive oxygen species, otherwise known as ‘free radicals’ or ‘pro-oxidants’.

These free radicals have been shown to reduce the flow of lymphatic fluid, by reducing the frequency of the contractions and the amount of fluid moved with each contraction. Selenium has the ability to reduce these levels of reactive oxygen species.

Conclusions

These authors concluded that sodium selenite is a suitable treatment for secondary lymphedema due to oral cancer surgery and they recommend that selenium be started immediately after surgery.

Selenium for Lymphedema Study #5 (Han, 2019)

This is the most recent of the lymphedema selenium studies and took place in Korea in 26 women with stage II and III breast cancer related lymphedema.

This was a randomized, double-blinded, placebo controlled trial, in other words, the gold standard in clinical research.

Fourteen were in the treatment group and they received 500 micrograms of Selenase® by IV injection dissolved in 50 ml of 0.9% saline for five times over two weeks.

The twelve women in the control group received an identical volume of saline by IV. All 26 women were educated on how to do their own manual lymphatic drainage.

Results

All 26 women had similar blood levels of selenium before the trial. As expected, only the fourteen that received the selenium by IV had an increase in their blood selenium levels at the two week test. This elevated level didn’t last though, it came back down to pre-supplement levels by one month after the last infusion.

Of the 14 women that received the selenium, 12 of them were stage III and 2 were stage II lymphedema at the beginning of the study. Nine of the 12 reduced from a stage III to stage II lymphedema, while none of the placebo group improved their staging. By one month post selenium, 10 of the 14 who received selenium had achieved and maintained a lower stage.

These authors concluded that, while they don’t know the exact mechanism of how the selenium reduced the lymphedema, they can confirm that it did. They support that sodium selenite supplementation could be a safe and cost-effective treatment for lymphedema.

Selenium and Lymphedema Final Thoughts

All of the five selenium and lymphedema studies demonstrated a positive result with no side-effects. But, the science seems to be moving incredibly slowly, with only five small studies done in twenty years.

Selenium seems to be a very reasonable addition to a lymphedema treatment plan that includes lymphedema diet plus manual lymphatic drainage, compression garments, skin care and exercise – together known as complex decongestive therapy.

I also see that there was a trial done at Princess Margaret Hospital in Toronto on sodium selenite but sadly the results were not published (ClinicalTrials.gov, 2010). But, I do see in a PDF document on the Princess Margaret Website called “Guide to Lymphedema”, there is a brief mention on selenium in a list that begins with “together we can discuss the less common ways of looking after lymphedema found in the community” which includes, kinesiology taping, hyperbaric oxygen, manual lymph drainage and selenium among other strategies.

However, I have yet to meet a client that has been recommended selenium for their lymphedema. If you have, then I’d love to hear of your experience with it!

There was a review published in 2016 that recommended further trials of selenium and lymphedema are needed to confirm the results to date and the specify the selenium dosage and duration (Pfister, 2016).

One of the recommendations of the Micke study published in 2003 is for “larger randomized trials with longer follow-ups”. But where are these studies? It’s been almost 20 years and the science hasn’t been done. Is this due to cost? No funding? No profit on the other side? I’m not sure, but I’m disappointed that this potentially helpful, seemingly low risk treatment has not been more aggressively studied.

Regarding the Zimmerman trial with selenium prescribed on the day of surgery and continued for three weeks. I would think in most people with cancer treatment this would not interfere with either radiation or chemotherapy as most oncologists would provide at least three weeks for recovery from surgery before giving more treatment…(and in many cases chemo and/or radiation comes before surgery).

But I still think it’s worth mentioning that most oncologists don’t want their patients to take anti-oxidants during chemotherapy or radiation. The idea being that anti-oxidants could inadvertently repair the cancer cells that chemo and radiation are designed to damage.

In fact, there is support for that concern, there was a study in breast cancer patients that showed that taking an anti-oxidant supplement before and during cancer treatment, increased the risk of recurrence and death by 40% (hazard ration1.4) (Ambrosone, 2020). Although this study didn’t specifically ask about selenium supplementation, it did include other anti-oxidants (vitamins C, A, E, carotenoids and coenzyme Q10).

It’s one more reason to discuss the possible use of selenium with your physician to consider all the factors in your individual situation. You would not want the anti-oxidant supplement (selenium) that you take to improve your lymphedema increasing your risk of recurrence of cancer.

If this is something you are considering for your lymphedema, I would recommend the following;

  • Ask your physician to read this blog post to get up to speed on the research (all the studies are hyperlinked in the reference section below for more detail)
  • Have your serum and whole blood selenium levels checked
  • If you do supplement, use the same form of selenium specified in 4 out of 5 studies, namely Selenase®
  • Discuss with your physician whether oral or IV is the right route for you
  • Discuss the right dosing regime. These are the dosages used in research to date;
    • 333 micrograms of Selenase® three times a day before meals (1000 ug total) for one week. Then 300 micrograms for two weeks. Then 100 micrograms for the remaining three months if they weighed less than 70 kg (154 lbs.) or 200 micrograms if they weighed more than 70 kg (Kasseroller, 2000)
    • 500 micrograms per day (dosage was 350 micrograms per metre2 body surface area) by mouth once a day for four to six weeks  (Micke, 2002)
    • 1000 micrograms of sodium selenite either IV or by mouth daily for three weeks starting prior to their oral surgery (Zimmerman, 2005)
    • 500 micrograms per day (350 micrograms/m2 body surface area) sodium selenite medication by mouth daily for a period of 4–6 weeks after radiotherapy (Bruns, 2004)
    • 500 micrograms of Selenase® by IV injection dissolved in 50 ml of 0.9% saline for five times over two weeks (Han, 2019)
  • Stop your trial after 3 weeks or after checking your blood levels
  • Continue with your manual lymphatic drainage, compression and lymphedema diet
  • Continue to work with your lymphedema therapist

Additional Lymphedema Blogs

If you enjoyed this blog, then check out;

Better yet, sign up to receive notice of my latest blogs that way you won’t miss out on important information.

Additional Resources for Lymphedema

  • Lymphedema Nutrition School
    • The Lymphedema Nutrition School exists as either a self-study program, which you work through at your own pace or the live group format, in which you meet live via zoom for 10 sessions.
    • The self study you can join at any time and the live group program has new programs beginning about every other month.
    • Find out more at Just Wellness Nutrition School were all the programs are hosted.

References for Supplements for the Lymphatic System

Ambrosone CB, Zirpoli GR, Hutson AD, McCann WE, McCann SE, Barlow WE, Kelly KM, Cannioto R, Sucheston-Campbell LE, Hershman DL, Unger JM, Moore HCF, Stewart JA, Isaacs C, Hobday TJ, Salim M, Hortobagyi GN, Gralow JR, Budd GT, Albain KS. Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221). J Clin Oncol. 2020 Mar 10;38(8):804-814. doi: 10.1200/JCO.19.01203. Epub 2019 Dec 19. PMID: 31855498; PMCID: PMC7062457.

Beigi AA, Sadeghi AM, Masoudpour H, Shirazinejad S, Mottaghi P. Intravenous pamidronate for refractory lymphedema. Iran Red Crescent Med J. 2011 Apr;13(4):263-6. Epub 2011 Apr 1. PMID: 22737476; PMCID: PMC3371959.

Bruns F, Büntzel J, Mücke R, Schönekaes K, Kisters K, Micke O. Selenium in the treatment of head and neck lymphedema. Med Princ Pract. 2004 Jul-Aug;13(4):185-90. doi: 10.1159/000078313. PMID: 15181321.

Clinical Trials.gov. NCT00188604The Use of Selenium to Treat Secondary Lymphedema – Breast Cancer. Last updated April 13, 2000. Accessed May 6, 2021.

Cooke JP. Lymphangiogenesis: a potential new therapy for lymphedema? Circulation. 2012 Feb 21;125(7):853-5. doi: 10.1161/CIRCULATIONAHA.111.083477. Epub 2012 Jan 24. PMID: 22275500; PMCID: PMC3357957.

Forte AJ, Boczar D, Huayllani MT, Lu X, McLaughlin SA. Pharmacotherapy Agents in Lymphedema Treatment: A Systematic Review. Cureus. 2019 Dec 5;11(12):e6300. doi: 10.7759/cureus.6300. PMID: 31815082; PMCID: PMC6897350.

Han HW, Yang EJ, Lee SM. Sodium Selenite Alleviates Breast Cancer-Related Lymphedema Independent of Antioxidant Defense SystemNutrients. 2019;11(5):1021. Published 2019 May 7. doi:10.3390/nu11051021

HealthLinkBC. Ketoprofen- Oral. Last updated, October 2018. Accessed April 28, 2021.

Kasseroller RG, Schrauzer GN. Treatment of secondary lymphedema of the arm with physical decongestive therapy and sodium selenite: a review. Am J Ther. 2000 Aug;7(4):273-9. doi: 10.1097/00045391-200007040-00008. PMID: 11486162.

Kitchen G, Garrett MJ. A trial of intra-lymphatic cyclophosphamide in patients with arm lymphoedema due to metastatic breast carcinoma. Clin Radiol. 1971 Jul;22(3):379-81. doi: 10.1016/s0009-9260(71)80088-0. PMID: 4326922.

Medline Plus. Pamidronate Injection. Last updated Dec 15, 2015. Accessed May 8, 2021.

Medline Plus. Terbutaline. Last updated May 15, 2017. Accessed May 3, 2021.

Medline Plus. Theophylline. Last updated Nov 15, 2019. Accessed May 3, 2021.

Micke O, Bruns F, Mücke R, Schäfer U, Glatzel M, DeVries AF, Schönekaes K, Kisters K, Büntzel J. Selenium in the treatment of radiation-associated secondary lymphedema. Int J Radiat Oncol Biol Phys. 2003 May 1;56(1):40-9. doi: 10.1016/s0360-3016(02)04390-0. PMID: 12694822.

Moore JC, Ballas ZK. A novel therapy for lymphedema. Arch Intern Med. 2009 Jan 26;169(2):201-2. doi: 10.1001/archinternmed.2008.580. PMID: 19171818.

National Institutes of Health, Office of Dietary Supplements. Selenium for Healthy Professionals. Last updated March 26, 2021. Accessed May 5, 2021.

Pfister C, Dawzcynski H, Schingale FJ. Sodium selenite and cancer related lymphedema: Biological and pharmacological effects. J Trace Elem Med Biol. 2016 Sep;37:111-116. doi: 10.1016/j.jtemb.2016.05.005. Epub 2016 May 24. PMID: 27267968.

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