The Benefits of Low-Carbohydrate, High-Fat (LCHF) Diet on Body Composition, Leg Volume, and Pain in Women with Lipedema

This study aimed to assess the potential benefits of a low-carbohydrate, high-fat (LCHF) diet on body composition, leg volume, and pain reduction in women with lipedema compared to overweight or women with obesity. The study included 113 female participants, 56 with lipedema and 57 with overweight/obesity (BMI >25 kg/m2) without lipedema. All subjects were prescribed a low-carbohydrate, high-fat (LCHF) diet with anti-inflammatory properties to adhere to for a duration of 7 months. Measurements of anthropometry, body weight, composition, and pain (VAS) were conducted at the study's commencement and conclusion. 52 participants completed the study. Both groups experienced a similar weight reduction, amounting to 12.9% compared to the baseline (−10.8 kg vs. −11.9 kg; p = 0.14, for lipedema and women with overweight/obesity, respectively). The most reduction was in body fat mass. Improvements in various parameters were observed, except for ankle circumferences, which decreased more in the lipedema group. Lipedema participants showed significantly reduced pain levels following the LCHF diet (4.6 ± 2.6 vs 3.0 ± 2.3; p  <  0.001). The LCHF diet holds promise for weight loss, body fat reduction, leg volume management, and pain alleviation in women with lipedema. These findings provide valuable insights into potential therapeutic strategies for lipedema management.


Introduction
Lipedema is a chronic and progressive condition that predominantly afects women.Clinical manifestations of lipedema include abnormal and disproportionate fat distribution between the legs and trunk, with adipose tissue accumulating symmetrically in the lower and/or upper extremities, sparing the hands and feet [1,2].
Te worldwide prevalence of lipedema was estimated to be approximately 11% [3,4].Te disease often manifests during hormonal changes, such as puberty, pregnancy, or menopause [5].Te cause of lipedema remains unknown, but several hypotheses about its pathophysiology have been proposed: genetic predisposition, hormonal infuence, fat cell changes, microvascular dysfunction, capillary damage, lymphatic disturbances, and infammation [1,5,6].Lipedema is often observed in familial clusters, suggesting a genetic component.It is thought to follow an autosomal dominant inheritance pattern with incomplete penetrance, with up to 60% of patients having afected frst-degree relatives.Lipedema tends to manifest during hormonal changes and is believed to be infuenced by estrogen.Changes in the distribution of estrogen receptors in fatty tissue may play a role.It is unclear whether lipedema involves an increase in the number of fat cells (hyperplasia) or enlargement of existing fat cells (hypertrophy).Studies suggest alterations in the initial stages of fat cell diferentiation.Primary dysfunction in lymphatic and blood capillaries may result from hypoxia due to excessive fat tissue expansion, leading to endothelial dysfunction and increased angiogenesis.It may also be linked to mechanical issues in lymph drainage.Capillary damage may lead to a greater tendency to form hematomas and petechiae.Increased capillary permeability can cause tissue edema, initially compensated for by increased lymph drainage, but insufciency may develop as the disorder progresses.Lymphatic scintigraphy shows early disturbances in lymphatic transport capacity.Capillary abnormalities can be worsened by issues in large blood vessels, like aorta stifness, which may lead to vascular remodeling and hypertension.Dysregulation of the veno-arterial refex (VAR) also contributes to edema and hematoma formation.Increased pain perception in lipedema may result from dysregulation of sensory nerve fbers due to infammation.Mechanical compression of nerve fbers by fatty tissue does not explain the pain as it does not occur in other types of lipohypertrophy or lymphedema [5,6].
Diagnosing lipedema may involve observing symptoms such as easy bruising and spontaneous or palpation-induced pain, which patients describe as burning, pressing, heavy, and increasing throughout the day.Afected individuals often experience sensations of heaviness and tightness in the afected extremities [7,8].Infammatory changes in the adipose tissue may contribute to the pain, but the exact underlying mechanisms are still not fully understood [1].
Lipedema can be classifed into four stages based on the severity of fat accumulation and skin changes.In the frst stage (mild), fat accumulation is mild, and the skin appears smooth and symmetrical, with a slight increase in the size of afected areas.Te second stage (moderate) exhibits more noticeable fat accumulation, resulting in a pear-shaped or column-like appearance of the legs, and the skin may develop small nodules.Te third stage (severe) is characterized by a substantial increase in volume, larger nodules, and increased skin irregularities.In the fourth stage (very severe), lipedema can lead to signifcant deformities and functional limitations, with marked enlargement and fbrosis of the legs [5,9,10].Additionally, lipedema is further classifed into fve types based on the distribution of fat and its appearance (type 1-buttocks, type 2-buttocks, hips, and thighs, type 3-buttocks, hips, thighs, and calves, type 4-arms, and type 5-calves) [5].
Conservative therapy for lipedema emphasizes promoting a healthy lifestyle, personalized weight control strategies, and graded activity training programs.As a signifcant proportion of lipedema patients are with overweight or obesity, dietary interventions play an essential role in management [1,8,13,14].Our previous research demonstrated that a low-carbohydrate, high-fat diet (LCHF) was more efective in lipedema treatment than diets with a low glycemic index [15].However, the efcacy of any diet in lipedema treatment may be enhanced by its antiinfammatory potential [16].
Studies have also suggested that LCHF diets can be benefcial for individuals with overweight or obesity, leading to decreased adiposity and appetite control through hormonal changes, including reduced levels of the hunger hormone leptin [17][18][19][20].Some authors have reported a reduction in perceived pain in lipedema patients following an LCHF diet [21][22][23].While the low-carbohydrate, high-fat (LCHF) diet has shown potential benefts for individuals with lipedema and patients with overweight/obesity, it is essential to be aware of potential nutritional defciencies that may arise from this dietary approach.LCHF diets emphasize high-fat and low-carbohydrate food sources, which can lead to a reduced intake of certain nutrients, such as fber, vitamins, and minerals [15,24].Tis study is notable for being the frst to directly compare the efects of a lowcarbohydrate, high-fat (LCHF) diet in individuals with lipedema to those dealing with overweight or obesity.Additionally, we thoroughly examined changes in both body composition and lower limb volume, a crucial aspect in evaluating the efectiveness of the diet for women with lipedema.Te assessment of pain further confrms the benefts of the LCHF diet across various aspects.
Our study aimed to determine the potential benefts of a low-carbohydrate, high-fat (LCHF) diet on body composition, leg volume, and pain reduction in women with lipedema compared to women with overweight/obesity.

Study Design.
Tis study encompassed a dietary intervention case-control design, characterized by its prospective nature spanning a duration of seven months.Notably, the study was conducted at a singular research center, ensuring controlled conditions for data collection and analysis.

Study Groups.
Te study enrolled a total of 113 female patients from the Angiology Outpatient Clinic at Wroclaw Medical University in Poland, including 56 with a diagnosis of lipedema based on typical clinical symptoms [10] and 57 with overweight or obesity (BMI >25 kg/m 2 ) but without lipedema.Exclusion criteria included pregnancy, breastfeeding, a period of 6 months after pregnancy, various medical conditions such as lymphedema, edema in the course of chronic vein insufciency or heart failure, diabetes mellitus, kidney or liver failure, hormonally unbalanced thyroid disease, cancer, and implanted devices.Figure 1 demonstrates the scheme of the research.Te study was conducted in accordance with the Declaration of Helsinki and approved by the Bioethics Committee at Wroclaw Medical University, Poland (KB-456/ 2019).Written informed consent was obtained from all participants.Te study was initiated in January 2021 and concluded in May 2022.Of the original study population, 52 patients (28 in the lipedema group and 24 with overweight/ obesity) completed the study.Lipedema patients were classifed into 4 clinical stages and 5 types of the disease based on established criteria [5].

Measurement of Anthropometric and Body Composition
Parameters.A TANITA HR-001 growth meter (Tanita, Japan) was used for height measurement.A TANITA MC-2 Journal of Obesity 780MA (Tanita, Japan) was used for weight and body composition parameters.Parameters such as body fat percentage (%), body fat (kg), lean body mass (kg), total body water (kg), and visceral fat level were obtained.Patients were instructed not to consume food or drink for minimum 4 hours, not to engage in vigorous physical activity for 12 hours, and not to use diuretics for 6 hours prior to the study.Body mass index (BMI) was calculated as the ratio of body weight (kg) to height (m) squared.Waist, hip, thigh, calf, and ankle circumferences were measured with a standard tape measure to the nearest 1 cm.Te mean value of the waist-hip ratio (WHR) was calculated as the ratio of waist to hip circumference.Leg circumferences were measured with a standard tape measure to the nearest 0.5 cm.Te measurements were taken at 4 cm intervals from the ankle to the groin on the side of the leg.Based on these measurements, we calculated the volume of the leg (in milliliters) using the equation for a truncated cone [25].

Assessment of Pain Level in the Leg.
Te study employed validated method to assess pain levels-the visual analog scale (VAS).Te visual analog scale is one of the most frequently used instruments to measure pain intensity.VAS is graphically represented by a graduated scale ranging from 0 (no pain at all) to 10 (full of pain), on which a patient indicates her perceived level of pain [26].Te VAS was assessed at baseline and after completing dietary intervention.

Dietary Intervention.
Te LCHF diet utilized a structure similar to a typical ketogenic diet, with less than 50 g of carbohydrates per day.Te diet was designed with a Mediterranean style and focused on the quality of the food consumed, with many food products chosen for their antiinfammatory properties.Te daily energy intake was divided into 3 meals, consisting of a source of protein, fat, and vegetable additives.Te sources of protein included eggs, cheese (such as Gouda, cheddar, feta, mozzarella, and full-fat quark), lean poultry, or beef, with the exclusion of animal protein sources such as pork, ofal, and fatty skin poultry.Te sources of fat included products high in MUFA (monounsaturated fatty acids), such as olive oil, avocado, olives, almonds, and hazelnuts, as well as PUFA (polyunsaturated fatty acids), such as canola and linen oil, walnuts, linen seeds, and oily marine fsh such as salmon, herring, mackerel, and sardines.Each meal also included non-starchy vegetables such as tomato, cucumber, pepper, spinach, sprouts, caulifower, zucchini, cabbage, radish, and Journal of Obesity aubergine, as well as one small portion (25−30 g) of berry fruits per day.Te LCHF diet was also enriched with herbs and spices with anti-infammatory properties, such as turmeric, cloves, garlic, thyme, rosemary, and black/green tea once a day.Additionally, in some cases, a daily snack consisting of nuts, seeds, or fresh vegetables was incorporated.Te most detailed description of our LCHF diet we provided in our previous study [15].Table 1 presents an exemplary 7-day dietary plan implemented among the subjects.
Te diet plans were personalized for each participant by a clinical dietician using DietetykPro software (DietetykPro, Wroclaw, Poland) in order to increase adherence to the diet.Te daily energy requirements for each participant were calculated based on their resting metabolic rate (RMR) and physical activity level (PAL) ratio.RMR was measured using the indirect calorimetry method with the Fitmate device (Cosmed, Rome, Italy) according to standard procedures [14].PAL was determined individually for each patient, typically ranging from 1.3 to 1.5 [27].Te energy intake for each participant was set at 75-85% of their total energy requirements based on their body weight.Te energy and nutritional status of diets was calculated based on the Polish Tables of Nutritional Value of Products and Dishes [28] and using the USDA (U.S.Department of Agriculture) food products database [29].
A 24 hour nutritional interview was conducted as part of regular monthly assessments, either through phone calls or personal visits.Specifc intervals during the study, at 2.5 and 5 months, were also utilized for data collection.Tese measures provided valuable information regarding participants' adherence to the prescribed diet.Tis approach allowed us to identify common dietary mistakes, such as the consumption of carbohydrate-rich products, meal skipping, or unnecessary fat restrictions.Participants who did not comply with the prescribed diet were excluded to maintain the integrity of the study and ensure consistency of the intervention across the study group.

Statistical Analysis.
Results are presented as mean values ± standard deviation or median and quartiles Q1 and Q3, when the data distribution was normal or non-normal, respectively.Te conformity of the distribution in the given variable to the normal distribution was verifed using the Shapiro-Wilk test.If the distribution signifcantly deviated from normal, we employed nonparametric tests, such as the Mann-Whitney U test for independent samples and the Wilcoxon test for repeated measurements.In cases where the distribution did not show a signifcant diference from normal, the T-test was used.To compare the diferences between baseline and fnal anthropometric and body composition measurements, three types of tests were used: T-test, Wilcoxon, and Mann-Whitney U tests (depending on the results of the test checking normality of distribution and the test checking the homogeneity of variation).Te Wilcoxon test was used to determine if there are diferences in the VAS before and after dietary intervention.Results for all analyses were considered statistically signifcant when p < 0.05.Te power of the used tests was analyzed posteriori.Given an alpha level of 0.05 and a II-type error (beta) of 0.2, with fnal group sizes of 24 and 28, the efect sizes are as follows: (i) for the t-test for independent groups, d � 0.79; (ii) for the Mann-Whitney test, d � 0.81; (iii) for the Wilcoxon test for matched pairs, d z � 0.79.Here, d represents |μ 1 -μ 2 |/σ for the t-test, d z represents |μ z |/σ z for the Wilcoxon test, where μ 1 and μ 2 are means in populations 1 and 2, σ is the standard deviation common to populations 1 and 2, μ z is the means of the diferences between matched pairs, σ z is the standard deviation of the diferences between matched pairs, and d is Cohen's efect size.STATISTICA v 13.0 from StatSoft Inc. (StatSoft Inc., USA) was used for statistical analysis of the results.

Results
Te study found that the median age of participants in the patients with lipedema was 39.0 (33.0, 62.0) years, while in the women with overweight/obesity, it was 49.0 (41.5, 59.0) years; however, the diference between the two groups was not statistically signifcant (p � 0.14).However, at baseline, there were signifcant diferences between the groups regarding waist and ankle circumferences, as indicated in Table 2. Additionally, the mean waist-to-hip ratio (WHR) was found to difer between the two groups, which is understandable given the disproportionate distribution of fat between the upper and lower body in lipedema females.
Te majority of women in the lipedema group were at stage 2, accounting for 50% of the group.Furthermore, type 3 lipedema was the most prevalent type, accounting for 67.9% of the group.Te prevalence of lipedema stages and types in the study group is presented in Figure 2.
Despite individualized diet plans in both groups, the composition of the diets did not difer signifcantly.In both groups were defcit of a fber, with the median intake being 34.4% and 35.2% of the daily recommendations for Polish adults in the lipedema and patients with overweight/obesity, respectively.Moreover, the diets in both groups were defcient in various essential nutrients, such as iron, magnesium, potassium, iodine, manganese, thiamine, calcium, folate, and vitamin D. Te detailed diet composition in both groups is presented in Table 3. Compliance with the recommended intake of vitamins and minerals in the study groups is presented in Figure 3. Te detailed comparison of vitamin and mineral intake with Polish recommended levels has been added to Table S1 in the supplementary materials.
After 7 months of following a low-carbohydrate, high-fat (LCHF) diet, participants in both groups experienced a reduction in body weight, with the majority of this reduction attributed to a decrease in body fat mass.Additionally, improvements in various anthropometric and body composition parameters were observed, with most of these improvements being statistically signifcant.Interestingly, there were no signifcant diferences between the lipedema and patients with overweight/obesity, except for ankle circumferences, which decreased more signifcantly in the lipedema group.Additionally, total body water did not change signifcantly in the lipedema group, in contrast to the patients with overweight/obesity, where it decreased.A comparison of anthropometric and body composition 4 Journal of Obesity Journal of Obesity measurements before and after dietary intervention in the study groups is presented in Table 4.
Te study fndings revealed a notable decrease in pain levels among participants with lipedema following a 7month adherence to the low-carbohydrate, high-fat (LCHF) diet, as assessed by visual analog scale (VAS) scores (Table 4).Te individual variations in perceived pain after implementing the LCHF diet are illustrated in Figure 4, demonstrating the impact of the dietary intervention on pain reduction in each participant.

Discussion
Te objective of this study was to examine the potential benefts of a low-carbohydrate, high-fat (LCHF) diet on body composition, leg volume, and pain reduction in women with lipedema compared to women with overweight/obesity.Te results of the study provide preliminary evidence supporting the viability of an LCHF diet as a treatment option for reducing leg volume and managing pain in individuals with lipedema.6 Journal of Obesity Te study's fndings revealed signifcant improvements in various parameters following the implementation of the LCHF diet.Notably, the women with lipedema and overweight/obesity experienced signifcant reductions in body weight, body fat mass, and leg volume.Tese results suggest that the LCHF diet may have a potential role in reducing adiposity and leg volume, irrespective of baseline body composition.Te reduction in body weight was predominantly attributed to a decrease in body fat mass, highlighting the efcacy of the LCHF diet in targeting fat loss, a desirable outcome in the context of obesity treatment.Furthermore, the reduction in visual analog scale (VAS) scores indicates a favorable impact of the LCHF diet on pain perception among the lipedema group.Tis suggests that the diet intervention not only addresses physiological changes but also contributes to improved subjective well-being in individuals with lipedema.
A meta-analysis conducted by Castellana et al. [30] encompassing adults with overweight and obesity demonstrated the efectiveness of a low-calorie ketogenic diet in reducing body weight, BMI, and waist circumferences.Tese fndings align with the present study, afrming the potential of ketogenic diets in promoting sustainable weight loss.In addition, the comparison between low-carbohydrate ketogenic diet (LCKD) and low-fat diet studies further substantiates the superiority of LCKD in body weight reduction and fat mass loss.Te study by Al Aamri et al. [31] showcased the pronounced efects of LCKD in comparison to a low-fat diet.Tis aligns with our fndings and reinforces the potential of LCHF diets to induce signifcant weight loss.Similarly, a meta-analysis conducted by Zhou et al. [18] and other individual studies [17,19] supports the notion that LCHF diets are efective in reducing body weight in individuals with overweight and obesity.Tis consistency in results underscores the robustness of the efect and the potential utility of LCHF diets as a weight management strategy.
Findings from other studies exploring LCHF diets in lipedema patients echo the present study's results.Te study involving a 7-week LCHF diet intervention reported reductions in body weight and body circumferences, along with pain reduction.Tis aligns with our fndings, emphasizing the potential of LCHF diets to address both physiological and pain-related aspects of lipedema.In one particular investigation involving nine women diagnosed with lipedema and exhibiting a BMI within the range of 30 to 45 kg/m 2 , a seven-week regimen of LCHF diet was administered.Tis dietary intervention comprised 70-75% energy from fats, 5-10% energy from carbohydrates, and 20% from protein.Te outcome of this dietary intervention manifested as a substantial decrease in body weight by approximately 4.1 kg and a reduction in various body circumferences.However, the change in fat mass was not statistically signifcant, with a decrease of only 1.5 kg.Additionally, a decrease in pain perception was reported following the LCHF diet.Remarkably, when the participants reverted to their standard diet after the intervention, they observed maintenance of body weight but experienced a recurrence of pain.Tis led to the conjecture that the pain relief might be attributed to the anti-infammatory potential of the LCHF diet itself, rather than solely to the weight loss induced by it [21].Te mechanisms underlying pain reduction following the LCHF diet in lipedema patients remain speculative.It is hypothesized that the reduction in leg volume may alleviate hypoxia, leading to a reduction in adipocyte hyperplasia and, subsequently, pain reduction.Further research is needed to elucidate these mechanisms and explore the potential anti-infammatory efects of LCHF diets in pain management.
Moreover, a case study reported signifcant body weight reduction and pain improvement following a ketogenic diet in a lipedema woman.In this instance, a ketogenic diet was employed, comprising 1300 kcal daily intake with 30% energy from proteins, 66% energy from fats, and 4% energy from carbohydrates.Furthermore, omega-3 fsh oil, along with vitamins C and D, was supplemented in her dietary plan.Remarkably, the woman exhibited a substantial reduction in body weight, amounting to 41 kg, which corresponded to a reduction of approximately 20% in body fat.Tis dietary intervention also improved pain perception, consequently enhancing her overall quality of life.However, the authors of this case study approached their conclusions with caution, refraining from asserting the ketogenic diet as the exclusive solution for lipedema treatment [22].Nevertheless, it is notable that our previous research corroborates the pronounced benefts of the ketogenic diet for achieving an efective reduction in body fat, particularly in the lower limbs, in lipedema-afected women [15,32].
Te constraints inherent to our study may arise from the challenge of discerning lipedema from obesity, particularly in cases where patients exhibit subtle lipedema symptoms or a higher degree of obesity.Nevertheless, our study employed rigorous criteria for group selection, and all female participants underwent a thorough evaluation by an angiologist.As a result, the potential for erroneous categorization within the study cohorts has been markedly minimized.
In conclusion, this study contributes valuable insights into the potential benefts of an LCHF diet for reducing weight, body fat mass, and leg volume and managing pain in women with lipedema.Te consistent fndings across various parameters, coupled with support from existing literature, underscore the potential therapeutic role of LCHF diets in addressing both physiological and subjective aspects of lipedema.Further research is warranted to validate these fndings, elucidate underlying mechanisms, and establish the long-term efcacy and safety of LCHF diets in lipedema treatment.Clinical practitioners may consider incorporating LCHF diets as a potential therapeutic strategy for managing

Figure 1 :
Figure 1: Te scheme of the research.

Figure 3 :
Figure 3: Compliance of vitamin and mineral intake with Polish recommendations (%) in study groups.

− 8 5 VASFigure 4 :
Figure 4: Change in pain level of each participant before and after dietary intervention in the lipedema group.

Table 1 :
Sample weekly nutritional plan in anti-infammatory LCHF diet.

Table 3 :
Diet composition in lipedema and overweight/obesity groups.

Table 4 :
Comparison of anthropometric and body composition measurements before and after dietary intervention in the study groups.