What is the Effect of Obesity on Lymphoedema?    

What is the Effect of Obesity on Lymphoedema? 
Clinical experience has shown that obesity inhibits the effective management of lymphoedema. 
An increase in the amount of adipose tissue (fat)  in the body causes greater pressure on lymphatic and blood vessels, particularly in the legs, adversely affecting lymphatic drainage and venous return to the heart. 
Generally speaking, obese people suffer from greater immobility so experience a reduced muscle pump effect from exercise. Sometimes  they have difficulty elevating their legs and are therefore less able to benefit from the effect of gravity in assisting lymph drainage. They may also have a poor body posture causing an increase in abdominal pressure and consequent reduced lymphatic drainage. Respiratory function can be impaired causing difficulty performing deep breathing exercises, so the respiratory pump effect is adversely affected. 
In addition, obese oedematous limbs are more difficult to massage and bandage adequately due to their size and shape, thus making treatment by physical means less effective. 
  
  
  

 
What is the Influence of Body Mass Index (BMI) on Lymphoedema?
The BMI is an accurate, universally accepted method of determining whether a person's weight is proportionate to their height. This was recommended in the USA by the National Institute of Health Consensus Development Conference in 1985 as an accurate index for the prediction of medically significant obesity. The body weight in kilograms is divided by the height in metres squared, the resultant number being the BMI number which is equally applicable to men and women. 
For example, in a person of height 1.75m and weight 75kg 
 
This is within the normal range of 20 - 25. 
  
Underweight range - below 20 BMI 
Normal weight range - 20 -25 BMI 
Overweight range - 25 - 27.3 BMI 
Obese range - over 27.3 BMI 
   Some authors claim that being overweight is a contributing factor in the onset of post-mastectomy secondary arm lymphoedema. Werner et al (1991) established a direct relationship between obesity and the development of secondary arm lymphoedema in a study of 282 patients who received breast surgery, axillary lymph node clearance and radiotherapy in the treatment of breast cancer. It was found that obese women (BMI over 27.3) had a risk of arm lymphoedema which was more than double that of the rest of the population (27.4% compared with 12.5%). These authors identified a high BMI as the single most powerful predictor of the development of arm lymphoedema after breast surgery management.  
Besides obesity being claimed to be a causative factor in the development of post-mastectomy lymphoedema, Bertelli et al (1992) claim that arm lymphoedema patients who increase their body weight post-operatively achieve less of a reduction of oedema from treatment than patients who receive the same treatment but who do not put on weight post-operatively. In a study of 120 patients with arm lymphoedema who received the same treatment, those who did not gain weight after their mastectomy achieved a 25% reduction of oedema.  
In summary, the foregoing evidence would appear to confirm the influence of a high Body Mass Index on lymphoedema in two ways. Firstly, people who are overweight who undergo surgery for breast cancer are twice as likely to develop post-operative secondary arm lymphoedema as those who are not overweight. Secondly, people with lymphoedema who put on weight after having undergone surgery for breast cancer achieve approximately half the reduction of oedema from treatment as those who do not put on weight post-operatively.  

BREAST CANCER LYMPHEDEMA:
ROLE OF INSULIN RESISTANCE/FOXC2
Not everyone with lymphedema is overweight - although to the uninformed eye the swollen limbs associated with lymphedema might seem to be a sign of obesity. People with lymphatic filariasis (a form of lymphedema in tropical countries) can have large limbs while at the same time be emaciated. 

 

In industrialized countries where obesity is common, being significantly overweight may aggravate an already serious condition - and where lymphedema doesn't exist - lead to the development of the condition by putting additional stress on the lymphatic system. 

However determining the level of overweight in people with lymphedema, can be a challenge in the face of the additional weight caused by the swelling. Accepted methods of calculating body weight may simply not apply. 

Cautions Health Canada "Special consideration is also needed when using the [body weight]classification system. It may underestimate or overestimate health risks in specific groups such as: young adults who have not reached full growth, adults who naturally have a very lean body build, highly muscular adults, adults over 65 years of age, and certain ethnic and racial groups." (Canadian Guidelines for Body Weight Classification in Adults - Quick Reference Tool for Professionals, 2003) 

To make matters more complicated, another condition, known as lipedema, where the lower limbs become enlarged through fatty deposits, can be confused with lymphedema, because the two conditions look similar and are often found at the same time in an individual. (See: An Interview with Rebecca Morris, founder of the National Lipedema Association) 

"It is the connection between the fatty tissues in our bodies and the lymphatic system which has really caught the attention of scientists around the world..."
But it is the connection between the fatty tissues in our bodies, such as lipids (fats absorbed through the lymphatics in the bowel) and adipose tissue (a specialized connective tissue that functions as the major storage site in the body for fat), and the lymphatic system which has really caught the attention of scientists around the world. Some experts are hoping that understanding that relationship may lead to better treatments - and potentially a cure for lymphedema and its sister condition - lipedema - in the future. 

"We did not start out with any intention of investigating the lymphatic system. It was a spin-off rather than my intention. We got into it when I became interested about the relationship between pathological obesity in humans who developed diabetes, lymphatic problems and related disorders and the natural obesity in wild animals - which are fat for part of the year because they need to function effectively in the wild - and remain healthy and active," says Dr. Caroline Pond, a scientist with Open University in the UK. Pond has been undertaking research on adipose tissue since the early 1980s and on its interactions with the lymphatic system since the early 1990s. 

"It worked out that adipose tissue that is found connected with the lymph nodes and probably with the lymph vessels has special properties that equip it to interact locally with the lymphoid cells. We tried to ask the question - what determines where the adipose tissue forms and where it doesn't - given that adipose tissues in different parts of the body have different properties and play different roles in the functioning of the body as a whole." 

"This specialized adipose tissue
seems to be a sort of private little lunch bag 
for the lymph vessels..."
Much to Pond and her colleagues' surprise, what they found was that adipose tissue associated with the lymphatic system never disappeared - even when the animals she studied were fasting. "This specialized adipose tissue seems to be a sort of private little lunch bag for the lymph vessels and the lymph nodes that provide just the material they wanted, when they wanted it.", says Pond. "When animals were deprived of food, these tissues did not contribute their share to the fasting situation." 

Although Pond was not able to undertake her experiments for longer than an eight-week period on her laboratory rats, she found that when lymph nodes were artificially stimulated to imitate a local infection, the long-term exposure to infection caused an increase in the mass of adipose tissue. 


This finding suggested support for the theories of health care professionals that untreated inflammation from infections could aggravate the swelling associated with lymphedema. (See: Changes in adipocytes and dendritic cells in lymph node containing adipose depots during and after many weeks of mild inflammation, Dawn Sadler, Christine Mattacks and Caroline Pond, J. Anat (2005) 207, pp 769-781) 
Pond, who is the author of a popular book on the biology of obesity and fats called: The Fats of Life (Cambridge University Press, 1998 - available from Amazon), is hoping her research will inspire others around the world to pursue more research in this area. 

On the other side of the Atlantic at St. Jude Hospital for Children in Memphis, Tennessee, Dr. Guillermo Oliver's research team reported in 2005 that leaky lymphatic vessels were the leading cause of adult onset obesity in a laboratory model. 

"Leaky lymphatic vessels were the leading cause
of adult onset obesity in a laboratory model."
Abnormal leakage of lymph fluid from the ruptured lymphatic vessels - caused by the absence of the Prox1 gene in laboratory mice - was stimulating the accumulation of fat, particularly in regions of the body rich in lymphatics (abdomen and thorax/chest). The Prox1 gene is required for development of the lymphatic system. None of Oliver's laboratory mice, however, showed any external signs of lymphedema. 
 

Oliver was just as surprised as Pond by the findings. "It's just a matter of common sense that if the blood vascular system have many diseases and disorders which are a consequence of defects in the blood vascular system, it is just as likely that there are many conditions which involve lymphatic defects. They exist but we don't recognize them because they are asymptomatic." 

"There are a lot of things we need to do to determine how Prox1-related obesity happens and how often it happens before we can determine how many people are affected by it. All of this will take time. All we know is that there could be, among the obese population, a group of individuals for whom being overweight could be caused by something else other than over-eating and lack of exercise." 

But says Oliver, "Dieting and exercising is always good. Whether you are obese or not. It is a matter of quality of life. Exercising is good for your state of mind, for your heart, for everything. So I would say, no matter what the cause of your obesity - it can only do good." 

"Eventually we hope to identify
what factor in the lymph
may be triggering the obesity..."
"We are not an obesity lab. We do basic research. So we will just keep doing what we have been doing, keeping an eye on what we can do to move this to the next level. We need to understand how lymphatics form in normal conditions because if you don't understand the basics, you cannot understand pathological conditions. Eventually we hope to identify what factor in the lymph may be triggering the obesity. 



We would like to understand what could be the cause of this extreme obesity. If we can find what it is maybe the clinicians can eventually identify a group of patients with this combination that means lymphatic defects. And maybe eventually in the future we can find a drug or a therapy that may some way attack or block whatever substance is responsible for promoting this form of obesity." 


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Obesity has been suggested as a major predictive factor for arm edema in breast cancer. 

At the May 2, 2006 annual meeting of the American Society of Breast Disease (ASBD) Lucy K. Helyer, MD, surgical oncology fellow, Princess Margaret Hospital University Health Network reported on recent findings from their study which confirms earlier research in this area. 

Dr. Helyer followed 137 women with breast cancer who underwent sentinel node biosys. Close to 36% of patients who were obsese developed lymphedema in contrast to about 16% of overweight patients, about 7% of normal weight patients and none in underweight patients. Other studies have previously shown a link between obesity and lymphedema. These include: Arm edema in conservatively managed breast cancer: obesity is a major predictive factor, Therapeutic Radiology, 1991, Jul: 180(1):18; Obesity and cancer: the risks, science, and potential management strategies, Oncology 2005 Jun; 19(7): 871-81). Authors Say and Donegan (A biostatistical evaluation of complications from mastectomy. Surg. Gynecol, 1974) have suggested that individuals who are overweight often have prolonged operations and multiple transfusions, leading to arm edema, which they attributed to poorer vascularity of overweight patients. Other authors such as Haagensen (Diseases of the Breast, Philadelphia: Saunders, 1971) have suggested that infection is more difficult to avoid in patients who are obese. 

"Being active is important to a woman's health, her self-esteem and can prevent obesity."
 

"I can't tell you what proportion of obese patients develop lymphedema, as we have not specifically looked at this," says Dr. Roanne Segal, who does research on fitness and adjuvant therapy for breast cancer patients at the Ottawa Hospital. "What I look at is lymphedema as it relates to exercise, and offer recommendations and referrals for individuals who either have or develop lymphedema. Being active is important to a woman's health, her self-esteem and can prevent obesity." 

While women who undergo adjuvant therapy for their breast cancer commonly gain weight, "We believe the reasons behind the weight gain by women who have breast cancer are multi-factoral," says Dr. Segal. "These can include chemotherapy, hormonal factors, changes in their dietary intake as well as their habitual levels of activity which may include exercise. Pre-menopausal women commonly gain more than post-menopausal women. And we have preliminary evidence linking higher re-occurrence rates and possible survival that is inferiorly affected by obesity. With post-menopausal women - the average weight gain is one pound per year. With the treatment we are pushing menopausal changes." 

"We have enough research challenging the myth that you can't exercise because of lymphedema..."
From our perspective we have done some research and are developing protocols in the area of exercise for women who have been treated for breast cancer. I think we can safely say that we have evidence that women can exercise safely, that is there is no evidence to suggest that in the setting of a properly prescribed resistance or weight training program, woman who have undergone an axillary surgery for breast cancer have an increase chance of developing lymphedema. 

We strongly advocate, however, that prior to exercise an evaluation of both the woman's physical fitness or readiness for exercise as well as arm measures are undertaken such that monitoring if possible. 

In the last several decades, there has been enough controversy over the issues of both the ability of the woman post treatment for breast cancer as well as the ability to perform activities using the upper extremities. That myth was founded in what "seemed" to make sense, based on the theory that axillary surgery would damage the lymphatic system in such a way and to a magnitude that upper arm exercises would cause damage. 

With the advent of both highly trained surgeons, minimization of surgery (sentile node biopsy and improved radiotherapy techniques), alterations to the lymphatic system are minimized. In addition there is now mounting evidence through large randomized clinical trials that these type of exercise programs are both safe without any increased incidence of lymphedema. We have enough research challenging the myth that you can't exercise because of lymphedema - that this belief is not as prevalent anymore for health care providers." 

"Dr. Brorson noticed increased adipose tissue ("fat wrapping")in the large and small intestines - common in patients with Crohn's disease, where inflammation plays an important role..."
 

At the 2005 International Society of Lymphology conference in Salvador, Brazil, Dr. Hakan Brorson, with the Malmo University Hospital, Sweden, reported on his observations of increased adipose tissue content in the involved areas of patients he has treated. Dr. Brorson has been using liposuction to treat patients with non-pitting lymphedema who do not respond to more conventional forms of treatment, for 11 years. 

Dr. Brorson studied 44 women who had received liposuction in his clinic for breast cancer related lymphedema and found a very high level of adipose tissue. He noticed increased adipose tissue ("fat wrapping"), in the large and small intestines - common in patients with Crohn's disease, where inflammation plays an important role. He suggested that further research be undertaken to determine whether anti-inflamatory medication might reduce the development of excess adipose tissue in patients with lymphedema. 

Dr. Terence Ryan, of Oxford University, presented similar themes in his presentation, "Adipose Tissue and Lymphatic Failure: is there more to this story?" His presentation noted that there is increasing support for the notion that a fat cell is not just a container of fat but an endrocrine organ and a cytokine activated cell. (Cytokines are soluble proteinaceous substances critical to the functioning of immune responses.) He suggested that the physiological imbalance of blood flow and lymphatic drainage leads to impaired clearance of lipids and its uptake by macrophages (white blood cells which ingest pathogens and expel waste materials). 

At the conference Ryan asked whether the segments of lymphoid tissue in the skin might stimulate an enlargement of adipose tissue there. He suggested that perhaps that the filariasis worm (responsible for lymphedema in tropical areas) might be attracted to the lymphatic nodes because of their metabolic relationship with fatty deposits. 

Some experts believe that obesity may be responsible for aggravating existing or underlying cases of lymphedema.
"As the population ages, we develop disorders such as lymphedema from previous cancer surgery or secondary lymphedema that result from previous radiation treatment. The biggest challenge we see with lymphedema and wound healing relates to lymphedema of the lower legs. The average age of patients with chronic wounds with diabetic foot problems is about 60 and persons with venous leg ulcers is about 70 years old," says Dr. Gary Sibbald, a dermatologist internist with the University of Toronto. 

"...there's a...group that relates to individuals who have increased body weight. In these individuals the venous return and the lymphatic return to the heart is obstructed so that lymphedema develops. This can be a vicious cycle, which requires working with the patient to control the weight problem." (See Lymphovenous Canada's interview with Dr. Sibbald) 

Says Ryan, "I have traveled to a number of countries advocating morbidity control. It was in Guyana that I finally concluded that obesity inhibits effective management, not just in individuals but in populations", (Lymphatic Filariasis and the International Society of Lymphology, Lymphology, Vol. 37, No. 3, Sept. 2004). "The knowledge that obesity is a rising epidemic draws attention to its cofactor in lymphatic filariasis. There are clinical facts that an obese person with lymphedema suffers from greater immobility, rarely takes a deep breath, cannot elevate, and has a body posture that aggravates lymph drainage. In obesity, the tissues are less responsive to massage and to compression, there is considerable additional venous loading, and the skin's barrier function is more easily breached." 



So it would seem to make sense for all of us to watch our weight and exercise whether we have lymphedema or not. 

"There are probably 25 reasons why you don't want anybody to be greater than ideal body weight and I'm not saying you have to make Twiggy people out of everybody," says Dr. Segal. "For hypertension, heart disease, diabetes, joint problems - normal body weight is better than being obese. 

"A huge segment of our population is grossly obese. The statistics are growing at an incredible rate and I don't think we have seen the tip of the iceberg. Particularly in the United States, in the next 10 or 15 years we are going to see a cohort of children who become teenagers, who are obese now. What happens when they become more sedentary as adults?" 




RESOURCES AND SOURCES:
Canadian Community Health Survey: obesity among children and adults, Statistics Canada, 2004 
The Obesity Epidemic in Canada, Sheena Starky, Economics Division, Library of Parliament, Parliamentary Information and Research Service, July 15, 2005 
The Elusive Adipose Connection, Lymphatic Research and Biology, Vol. 2, Number 3, 2004 
Adipose tissue and the immune system, Caroline Pond, Prostaglandins, Leukotriens and Essential Fatty Acids 73 (2005) 17-30 
Site-specific differences in fatty acid composition of dendritic cells and associated adipose tissue in popliteal depot, mesentery, and omentum and their modulation by chronic inflammation and dietary lipids, Christine Mattacks, Dawn Sadler, and Caroline Pond, Lymphatic Research and Biology, Volume 2, Number 2, 2004 
Fatty acid compositions of lipids in mesenteric adipose tissue and lymphoid cells in patients with and without Crohn's disease and their therapeutic implications, Edward Westcostt, Alastair Windsor, Christine Mattacks, Caroline Pond and Stella Knight, Inflamm Bowel Dis, Number 9, Sept. 2005 
Changes in adipocytes and dendritic cells in lymph node containing adipose depots during and after many weeks of mild inflammation, Dawn Sadler, Christine Mattacks and Caroline Pond, J. Anat (2005) 207, pp 769-781) 
Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity. Harvey NL, Srinivasan RS, Dillard ME, Johnson NC, Witte MH, Boyd K, Sleeman MW, Oliver G. Nat Genet. 2005 Oct; 37(10):1072-81. Epub 2005 Sep 18. 
The lymphatic vasculature: recent progress and paradigms. Oliver G, Alitalo K. Annu Rev Cell Dev Biol. 2005; 21:457-83. 
The rediscovery of the lymphatic system: old and new insights into the development and biological function of the lymphatic vasculature. Oliver G, Detmar M. Genes Dev. 2002 Apr 1; 16(7):773-83. 
Obesity and cancer: the risks, science and potential management strategies. McTiernan, Anne, Oncology (Williston Park), 2005 Jun: 19(7):871-81 
Arm edema in conservatively managed breast cancer: obesity as a major predictive factor. Werner, RS, McCormick, B, Petrek J, Cox L, Cirrincione C, Gray JR, Yaholm J. Radiology, 1991 July: 180(1); 177-84 
Lymphatic Filariasis and the International Society of Lymphology: Adipose Tissue. TJ Ryan, Lymphology, Vol. 37, No. 3, Sept. 2004. 
Lower risk of fat formation and fibrosis if lymphedema is treated in time. Brorson H. Lakartidningen. 2005 Aug 8-21; 102(32-33):2220-5. 
Adipose tissue in lymphedema: the ignorance of adipose tissue in lymphedema. Brorson H. Lymphology. 2004 Dec; 37(4):175-7. 
Microlymphatic aneurysms in patients with lipedema. Amann-Vesti BR, Franzeck UK, Bollinger A. Lymphology. 2001 Dec; 34(4):170-5. 
The role of operative management of varicose veins in patients with lymphedema and/or lipedema of the legs. Foldi M, Idiazabal G. Lymphology. 2000 Dec; 33(4):167-71. 
Lipedema complicated by lymphedema of the abdominal wall and lower limbs. Zelikovski A, Haddad M, Koren A, Avrahami R, Loewinger J. Lymphology. 2000 Jun; 33(2):43-6. 
No lymphedema, no obesity. How can lipedema be treated? Stiefelhagen P. MMW Fortschr Med. 2001 Sep 6; 143(35-36):15. 
Lymphedema, lipedema, and the open wound: the role of compression therapy. Macdonald JM, Sims N, Mayrovitz HN. Surg Clin North Am. 2003 Jun; 83(3):639-58.