Ketogenic Diet: A Nutritional Therapeutic Tool for Lipedema?

Abstract

Purpose of review: This review aims to provide an overview of the current evidence on the efficacy, also considering the anti-inflammatory properties and safety of very low-calorie ketogenic diet (VLCKD) as a potential treatment for lipedema, particularly in the context of obesity.

Recent findings: Lipedema is a chronic disease characterized by abnormal and painful fat buildup on the legs and/or arms. It is often misdiagnosed as obesity or lymphedema. However, although lipedema and obesity can coexist, unlike obesity, lipedema usually affects the legs and thighs without affecting the feet or hands, and the abnormal deposition of adipose tissue in lipedema is painful. The current lifestyle interventions are often unsuccessful in the management of lipedema. There is no consensus on the most effective nutritional approach for managing lipedema. Recent studies have suggested that VLCKD may be an effective treatment for lipedema, demonstrating that it is also superior to other nutritional approaches such as Mediterranean diet or intermittent fasting. Lipedema is a chronic and debilitating disease characterized by abnormal and painful accumulation of adipose tissue in the legs. VLCKD has been shown to be an effective treatment for lipedema, especially in the context of obesity, due to its anti-inflammatory properties. However, further research is needed to determine the long-term safety and efficacy of VLCKD as a treatment for lipedema.

Keywords: Diet; Fat; Inflammation; Lipedema; Nutrition; Obesity; Very low-calorie ketogenic diet.

Fig. 1

Macroscopic and microscopic features of subcutaneous tissue in lipedema. Lipedema is characterized by an increased accumulation of SAT in terms of augmented number of adipocytes (hyperplasia) due to the upregulation of mitotic clonal expansion genes. Such SAT expansion, accompanied by increased lipid accumulation within the adipocyte (hypertrophy), is responsible for (i) recruitment of immune cells and (ii) ECM rearrangement (increased Na+ concentration, collagen deposition, and alterations of proteoglycans and glycosaminoglycans). These two events result, on the one hand, in triggering inflammation and, on the other hand, in promoting pathogenic alterations of both vascular and lymphatic functions that, in turn, determine IF accumulation and IS expansion. The excessive IF surrounding adipocytes represents a source of nutrients, thus further promoting fat cell hypertrophy. Abbreviations: SAT, subcutaneous adipose tissue; ECM, extracellular matrix; IF, interstitial fluids; IS, interstitial space

Fig. 2

The obesity-lipedema-inflammation vicious cycle. Obesity is a typical lipedema feature, but it is not an exclusive condition. These two phenotypes, however, are strongly related, with a bi-directional relationship. Both conditions are characterized by fat accumulation at the visceral but also subcutaneous level, especially in the upper and lower limbs, in the higher entity (grater SAT expansion) in lipedema. Obesity and lipedema can be mutually converted into each other, and both contribute to trigger and/or exacerbate a flogosis status, contributing to the development of a chronic low-grade inflammation condition. Inflammation, in turn, is responsible for impairment in vascular and lymphatic function, insulin resistance, empowerment of androgenic activity, and the development of metabolic disorders that contribute to further accumulation of adipose tissue, promoting hypertrophic and hyperplastic processes, thus perpetuating the cycle. Abbreviation: SAT, subcutaneous adipose tissue

Fig. 3

Very low-calorie ketogenic diet (VLCKD) for subjects with lipedema. Lipedema is often misdiagnosed as obesity or lymphedema, but its adipose tissue accumulation is resistant to lifestyle interventions. Nutritional strategies such as the VLCKD have shown potential for reducing inflammation, which is a significant contributor to lipedema’s pathogenesis. However, the evidence for the efficacy and safety of VLCKD in the treatment of lipedema is currently limited, and more research is needed to establish its efficacy