Lipoedema: What We Do Know

Lipoedema is a disorder characterized by an excessive accumulation of subcutaneous body fat, characterized by pain or soreness as well as accumulation of fat deposits, particularly in the extremities. The onset of lipoedema often occurs at times of female hormonal change such as puberty, during pregnancy, perimenopause or menopause.

The pathophysiology of the pain is not fully understood, but increased inflammation, compression of peripheral nerves by proliferating adipose tissue, and fluid accumulation in the area occupied by lipedema have been implicated as possible causes.​​​
​​But, what we do know: ​​


1. Lipoedema is chronic-low grade inflammatory condition. The SAT (subcutaneous adipose tissue) is inflamed with the formation of fibrotic tissue. The vascular system is also inflamed with leaky vessels, and the lymphatics become inflamed with the progression of lipoedema.
​Anti-inflammatory diet and nutraceuticals could be possibly helpful to control swellings and pain and  reduce tissue inflammation
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2. When there is chronic inflammation there is always Histamine involved.
 It is suggested that Histamine released by mass cells causes pain, swellings, itching in the interstitial tissue.  Chronic inflammation-induced, mass cells dependent dysfunction of lymph vessels may cause significant local stasis of lymph, and increased number of lymph protein. The result of this -  altered tissue environment as it is seen in lipoedema, lymphedema, and local fibrotic tissue.
Testing histamine intolerance, reducing consumption of high histamine foods and high inflammatory foods, taking the supplements which help to break down histamine and lower inflammation, could be beneficial in lipoedema management. ​
3. Oestrogen as a Contributing Factor to the development of lipoedema. 
Oestrogen control the distribution of body fat and food intake, regulate leptin expression, increase insulin sensitivity, and reduce inflammation through signaling pathways mediated by its receptors, estrogen receptor alpha (ERα) and ERβ. The decrease of ERα and increased ERβ concentration results in excess fat commonly stored in the gluteal-femoral region. Fluctuation of hormones in perimenopause, the drop of oestrogen in menopause/postmenopause may contribute to lipoedema development. 
Functional testing of hormones and oestrogen metabolites, and how efficiently oestrogen is neutralised and cleared out is necessary in to prescribe personalised nutrition and nutraceutical plan to balance hormones, reduce inflammation and manage further lipoedema development. ​
While exact aetiology of lipedema remains unclear, genetic factors are believed to play a significant role. Emerging researches suggest that gene polymorphisms (variations in DNA sequences) may contribute to susceptibility, progression, or clinical manifestations of lipedema.

Potential Gene Polymorphisms Associated with Lipedema​:

1. Hormone-Related Genes
  • Lipedema predominantly affects women, suggesting a hormonal influence. Polymorphisms in estrogen receptor genes (ESR1, ESR2) or COMT, gene involved in estrogen metabolism may contribute to fat distribution and vascular dysfunction.
  • FSHR (Follicle-Stimulating Hormone Receptor) gene variants have been explored due to their role in adipose tissue regulation.
2. Adipogenesis and Fat Metabolism Genes
  
  • PPARγ (Peroxisome Proliferator-Activated Receptor Gamma)– A master regulator of adipogenesis; polymorphisms may influence fat storage and distribution.
  • LEP (Leptin) & LEPR (Leptin Receptor) – Polymorphisms may alter satiety signaling and fat storage.

3. Inflammatory and Immune-Related Genes  
  • TNF-α (Tumor Necrosis Factor Alpha), Polymorphisms may contribute to chronic low-grade inflammation in lipedema.
  • IL6 (Interleukin-6) – unregulated in some lipedema patients; genetic variants could influence inflammatory responses.
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4. Detoxification genes:
  • Slow CYP1A1/CYP3A4 variants are linked to reduced estrogen breakdown and increased fat storage.  
  • Dysfunctional CYP1B1 has been associated with poor estrogen conversion and increased 4-HO therefore accumulation of fibrotic painful fat.  
  • CYP450 polymorphisms slow down detoxification of environmental toxins/endocrine disruptors making lipedema worse 
Life Code Gx nutrigenomics tests provides  personalised insights into your genetic makeup, helps to identify what influence Lipedema development and progression, and to tailor personalised treatment.
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