The term “Obesity paradox,” also sometimes called “reverse epidemiology” refers to the growing evidence that obesity in individuals with cardiovascular, pulmonary or renal disease leads to better overall outcomes in terms of reduced mortality both in and out of the hospital, reduced morbidity, and improved survival rates.1 It is crucial to know what obesity is, which the World Health Organization (WHO) defines as “abnormal or excessive fat accumulation that presents a health risk.2 Objectively, Body Mass Index (BMI) is used to categorize obesity and individuals with a BMI of more than or equal to 30 are classified as obese whereas overweight is defined as a BMI of greater than or equal to 25. (Table 1) As per the available factsheets provided by the WHO, as of 2022, 2.5 billion of the world population falls under the overweight category with around 890 million people living with obesity.3 Per predictions, by 2030, nearly 1 in 2 people in the United States will fall under the umbrella of obesity with a prevalence of >50 % in around 29 states.4 Besides the BMI, there are other indices which can be used to evaluate obesity and include waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtR), abdominal volume index (AVI), conicity index (CI), and new unconventional indicators like body shape index (ABSI), and body roundness index (BRI).5,6 Obesity is a metabolic issue and affects multiple organ systems increasing the risk of heart failure, coronary artery disease, atrial fibrillation, and venous thromboembolism [cardiovascular system], stroke and idiopathic intracranial hypertension [neurology], obstructive sleep apnea and obesity hypoventilation syndrome [pulmonary], diabetes mellitus, dyslipidemia, and metabolic syndrome [endocrine], metabolic dysfunction associated fatty liver disease and cholelithisis [gastrointestinal].7 There are multiple postulated mechanisms that have been discussed regarding the obesity paradox. Firstly, obesity offers muscle and fat reserves that buffer metabolic consequences, while higher cholesterol levels may neutralize endotoxins, reducing inflammation in chronic heart failure. Secondly, lower NT-proBNP levels in obese patients after myocardial infarction suggest improved outcomes and moreover, obesity is linked to reduced prothrombotic factors, better endothelial function, and increased ghrelin production, enhancing cardiac contractility. Soluble TNF-α receptors and adipokines offer cardioprotective benefits, while endothelial progenitor cells aid myocardial regeneration and lastly, in cancer, obesity is associated with less aggressive tumors and better treatment outcomes.1 Obesity paradox describes counterintuitive findings of improved outcomes and therefore it is essential to confirm the findings published in the literature.8 and multiple studies have been done pertaining to this issue however none of them have been able to come up with a definite conclusion or mechanism and one of the major factor contributing to this discrepancy is using BMI rather than total body fat composition is the indicator and ignoring the various confounders like age, existing comorbidities, socioeconomic background, and more.9 With the help of this review, we have tried to summarize various studies that have discussed obesity paradox in commonly occuring conditions like in critically ill patients, patients with cardiovascular diseases, chronic kidney disease, and malignancy.

The obesity paradox is associated with a decreased risk of cardiovascular, cancer, and chronic kidney disease, and various hypotheses have postulated the beneficial effect of obesity on these systems. Patients with cardiovascular diseases, chronic kidney disease, and cancer are generally suffering from malnutrition–inflammation complex syndrome (MICS) as they are generally cachectic, hypoalbuminemia, with muscular atrophy, along with an inflammatory syndrome and increased tumor necrosis factor (TNF)-alpha, which can result in bacterial or endotoxin translocation and are more susceptible to the ravages of inflammatory diseases.10 In addition, patients with malnutrition also suffer from lower levels of total cholesterol and lipoproteins, which is directly proportional to the mortality in these patients. However, patients who are above the BMI of 25kg/m2 generally have better nutritional status with higher levels of lipopolysaccharides and higher total cholesterol levels, which provide an adequate amount of lipoproteins, which can actively bind to and eliminate circulating endotoxins, thus reducing their harmful effects in causing inflammation and subsequent atherosclerosis.11 In addition, Patients who are above the BMI of 25kg/m2 tend to have lower levels of prothrombotic factors (e.g., thromboxane B2) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, which protect against cardiovascular disease. The release of NT-proBNP by cardiomyocytes due to increased wall tension may be considered a significant prognostic factor for mortality in acute coronary disease with thromboxane B2 levels correlated negatively with BMI and leptin, which is paradoxically better in subjects with BMI above 30kg/m2.12 Furthermore, the increased mobilization of endothelial progenitor cells may protect patients with BMI above 40kg/m2 from atherosclerosis by promoting the regeneration of the damaged myocardium and neoangiogenesis. This process ultimately leads to a reduction in afterload due to higher flow-mediated dilation and lower intima-media thickness. It also enhances myocardial contractile function and metabolic processes in cardiomyocytes while reducing apoptosis and fibrosis of the myocardium.1,13

Obesity significantly affects cardiovascular (CV) physiology, leading to hemodynamic and structural changes such as increased blood volume, cardiac output, and left ventricular (LV) filling pressures, especially in severe obesity. These changes contribute to left ventricular hypertrophy (LVH), altered LV geometry (both concentric and eccentric), and impaired systolic and diastolic function. Notably, diastolic dysfunction prevalence escalates with increasing obesity severity, being highest in Class III obese individuals.

Despite these adverse effects, multiple studies have revealed an obesity paradox in heart failure—where overweight and mildly obese patients exhibit better prognosis than normal-weight individuals. This paradox has been consistently demonstrated across studies and meta-analyses, particularly in Class I and II obesity. Proposed mechanisms include increased metabolic reserves, lower circulating natriuretic peptide levels (resulting in earlier HF diagnosis), and improved tolerance to cardioprotective therapies. However, this protective effect diminishes in Class III (morbid) obesity, where long-term outcomes worsen. Additionally, sex-specific effects are noted: overweight women with HF demonstrate a modest survival benefit, while this benefit is inconsistent or reversed in men after adjusting for confounders. A key modifier of this paradox is cardiorespiratory fitness (CRF). Studies show that individuals with preserved CRF (e.g., peak VO₂ ≥14 mL/kg/min) fare better irrespective of BMI, whereas those with low CRF and low BMI face significantly higher mortality. These findings underscore that fitness, not fatness, may be more prognostically relevant. The interplay between frailty, cachexia, and HF also provides critical context. Weight loss, particularly unintentional, is a powerful predictor of mortality, representing the “reverse” of the obesity paradox. Cachexia, marked by fat and lean mass loss, signals poor outcomes, and often accompanies right ventricular dysfunction.14,15

Obesity also appears to be linked to lower-stage cancer, smaller tumor size, and less aggressive biological subtypes. Additionally, being overweight or obese may have a positive impact on treatment outcomes, as excess adipose tissue can affect how the body processes cancer treatment drugs and provide a nutritional supply for surgical and anticancer treatments.1, 16 Researchers have proposed various mechanisms to explain the protective role of obesity in HF. Similar to coronary heart disease (CHD), patients with BMI above 30kg/m2 tend to be younger than their lean counterparts. Additionally, HF may be diagnosed at an earlier stage in patients with BMI above 30kg/m2 due to symptoms associated with elevated weight, such as dyspnea and edema (lead time bias).17 In addition, circulating levels of B-type natriuretic peptide (BNP) are lower in individuals with BMI of 25kg/m2 suffering from acute and chronic HF compared to individuals with BMI <18kg/m2, potentially leading to an earlier clinical presentation and better prognosis.11 Furthermore, Higher arterial pressure values in individuals with BMI of >30kg/m2 may allow for more intensive treatment with cardioprotective medications such as beta-blockers and renin-angiotensin-aldosterone system inhibitors. Finally, cardiorespiratory fitness may influence the obesity paradox in HF patients. Some authors have proposed the "compulsory exercise" hypothesis, suggesting that obesity requires more physical activity, which is recommended in HF and may explain the better prognosis in these patients.18 In addition, as stated obesity do significantly increases the risk of developing heart failure (HF), yet paradoxically, obese patients with established HF exhibit better survival outcomes compared to their leaner counterparts. This "obesity paradox" may be explained by greater metabolic reserves, attenuated neurohormonal activation, and reduced cardiac stress in obese individuals. However, using BMI as a surrogate for adiposity limits insight, as it does not distinguish between fat and lean body mass. Emerging data suggest that favorable body composition and preserved muscle mass, rather than adiposity alone, may mediate this paradox.19

Obesity is seen in around 20 % of the patients admitted to the Intensive Care Unit (ICU). It increases the risk of various clinical conditions like diabetes mellitus, cardiovascular diseases, hypertension, obesity hypoventilation syndrome etc.. Despite its association with increased morbidity and mortality in the general population, several studies have reported better outcomes in obese patients compared to their non-obese counterparts admitted to the ICU.20 The potential mechanism of obesity paradox in the critically ill ICU patients remains the same as in any other areas of observed paradox and include greater metabolic reserve, protective cytokine release, and hormonal changes in insulin, adiponectin, leptins etc.21 This ever so debatable “obesity paradox” has been studied using various parameters like in-hospital mortality rates, length of ICU stay, post-ICU discharge critical illness, mortality, survival rates, and quality of life and has been observed in a range of common critical conditions like circulatory shock, bacterial or viral pneumonia. Plecko et al. included 259,177 patients of age greater than 18 who were admitted to the ICU and found that there was lower hospital mortality with an average decrease of 2 % and 3.25 % for the 25–30, 30–35 kg/m2 groups compared to patients with a BMI of <24.9 kg/m2 and patients with a BMI of greater than 25 kg/m2 had a lower risk of hypoglycemic episodes which in turn might have led to the mortality benefit.22 Evaluating 2882 patients admitted with septic shock, Arabi et al. observed that obese patients had lower hospital mortality compared to normal weight patients.23. Besides circulatory shock, respiratory failure is another common indication of ICU admission and Sasabuchi et al. found that a obesity was associated with lower hospital mortality in mechanically ventilated patients whereas non-mechanically ventilated patients showed a J-curve association.24 Another study done in Australia & New Zealand concluded that increasing BMI was associated with a decrease in hospital mortality with 11.9 % in the underweight group in comparison to 5.3 % in patients with class II obesity.25 A multicenter cohort study looked at the in-hospital mortality and 28-day mortality in patients admitted to the ICU for the management of COVID-19, non-COVID viral and bacterial pneumonia. During the subgroup analysis, it was concluded the obesity paradox was true for both non-COVID and bacterial pneumonia groups however in-hospital mortality and 28-day mortality was similar in patients with all BMI categories in COVID-19 pneumonia group.26 On the contrary, another study done in New Zealand and Australia found that patients admitted for COVID-19 pneumonia, those with a BMI > 40 had an improved survival time of up to 2- years compared to the rest of the groups.27 Looking at the patients who were successfully discharged from the Intensive Care Unit (ICU), a study found that patients with a BMI>30 i.e. who were classified as obese had a lower 4 year hazard ratio for post-discharge mortality at 28 % as compared to 62 % seen in the underweight group (BMI<18.5).28 We can list endless data on the obesity paradox in critically ill patients however it is important to understand the clinical relevance. Many researchers feel that most of these studies had some confounding and selection biases as they did not account for any existing comorbidities and the fact that there is paucity of literature on how pharmacokinetics of drugs changes during a critical illness in obese patients.28

Coronary Heart Disease is often linked to high BMI of >30kg/m2, but various new studies have shown the paradoxical correlation between them.29 A study conducted with 529 consecutive patients with coronary heart disease (CHD) participating in cardiac rehabilitation and exercise training (CRET) programs found that patients with a BMI of 25 kg/m² or higher (393 patients) had a lower mortality rate compared to patients with a BMI lower than 25 kg/m² (136 patients) (4.1 % vs. 13.2 %, P < 0.001).30 Similarly, a study conducted by Romero-Corral et al., analyzing 40 studies involving nearly 250,000 patients, found that patients with a BMI of 25 kg/m² or higher and with coronary heart disease (CHD) had a lower risk of total and cardiovascular mortality compared to underweight and normal-weight patients.31 In another study by Buettner et al. assessing the impact of BMI of 30 kg/m² on outcomes after unstable angina (UA) / non-ST-segment elevation MI (NSTEMI) in 1676 patients treated with an early invasive strategy found that at three years, there was a notable decrease in all-cause mortality: from 9.9 % for patients with a normal BMI, to 7.7 % for overweight patients, to 3.6 % for BMI of 30 kg/m² patients.31,32 In a trial examining the glycoprotein IIb/IIIa inhibitor, abciximab, in patients with UA/NSTEMI not scheduled for coronary intervention, lower body weight was associated with increased 1-year mortality (9.6 % in the < 75 kg group compared with 7.4 % and 6.6 % in patients weighing 75–90 kg and > 90 kg, respectively [P < 0.001]). The finding of a better prognosis in obese CHD patients receiving contemporary treatment is further supported by data from large angioplasty registries and revascularization trials.33 Similarly in a study by Minutello et al. reported the protective effect of obesity in a study involving 95,435 consecutive patients who underwent percutaneous coronary intervention (PCI) over four years. Compared to healthy-weight patients, those with class I (BMI 30–34.9 kg/m2) or class II (BMI 35–39.9 kg/m2) obesity had lower in-hospital mortality and major adverse cardiac events. On the other hand, patients at both extremes (underweight [BMI < 18.5 kg/m2] and class III obesity [BMI > 40 kg/m2]) had significantly higher mortality and event rates.34 Similarly, Gruberg et al. studied 9633 consecutive patients with mainly stable coronary heart disease (CHD) undergoing PCI. found that normal-weight patients had worse clinical outcomes compared to overweight and obese patients despite having better baseline cardiovascular risk profiles and similar angiographic coronary artery disease (CAD) among all BMI groups. Complications such as hypotension, pulmonary edema, renal function worsening, major bleeding, access-site hematoma, vascular complications, and 1-year overall mortality rates were significantly higher in patients with BMI of 18kg/m2 to 24.9kg/m2 compared with patients with BMI of >25kg/m2.35,36 In a recent study on patients with a previous history of PCI, Uretsky et al. found approximately a 40 % relative risk reduction for the primary outcome, including all-cause mortality, non-fatal myocardial infarction (MI), and non-fatal stroke in overweight and obese patients.37 A recent systematic review of cohort studies on patients with coronary artery disease (CAD) found that lower overall and cardiovascular mortalities were observed in overweight and moderately obese patients. It is important to note that obese and overweight patients who develop coronary heart disease are, on average, younger than lean patients and have a higher left ventricular ejection fraction. Another novel study suggests that obese patients who experience acute myocardial infarction (AMI) tend to have less severe and complex coronary artery disease (CAD) compared to non-obese individuals. This indicates a potential physiological mechanism for this observation.38 Furthermore, a recent meta-analysis by Tan and colleagues demonstrated that obese and overweight patients who undergo percutaneous coronary intervention (PCI) are more likely to receive intensive medication treatment with aspirin, β-blockers, and statins, which may contribute to reduced hospitalization time and lower short- and long-term mortality rate.39 However, a large retrospective study found that overweight and obese patients have higher survival rates after AMI, even after accounting for age and medication treatment. Additionally, measurements of adiposity, such as waist-to-hip ratio (WHR), were positively correlated with obesity and CAD.38 In conclusion, obese and non-obese individuals may develop cardiovascular disease through different mechanisms due to their distinct cardiovascular risk factors, suggesting that they should be considered as two separate populations.Although Hypertension is a common risk factor for obesity, there has been a paradoxical relation between higher BMI and better prognosis in patients diagnosed with HTN. Uretsky et al. found that in the International Verapamil SR-Trandolapril Study (INVEST) cohort, overweight and obese patients with treated high blood pressure and known coronary heart disease had a nearly 30 % lower all-cause mortality rate at 24 months.40 Similar findings were reported in other studies, such as the Systolic Hypertension in the Elderly Program (SHEP) study and the Hypertension Detection and Follow-Up Program (HDFP), with overweight patients showing a decreased risk of stroke and total mortality compared to lean patients. In summary, there appears to be an unexpected relationship between BMI, essential hypertension, and mortality, with the lowest risk observed at a BMI of 28 to 29 kg/m2 for total mortality and CV-terminating events.Obesity is associated with hypertension and coronary artery disease, both of which are associated with heart failure (HF).41 Additionally, excessive body weight can cause left ventricle remodeling, leading to systolic and diastolic dysfunctions. However, recent studies have indicated that obesity may be linked to improved survival in HF. A recent meta-analysis involving 22,807 participants showed that individuals with BMI of <18kg/m2 had the highest risk of adverse events, including cardiovascular mortality, all-cause mortality, and re-hospitalizations, during a mean 2.9-year follow-up.42 Conversely, those with an BMI of >25kg/m2 had the lowest risk. Another study involving 6142 patients with acutely decompensated HF from 12 prospective studies found a strong obesity paradox, mainly in older HF patients, those with reduced left ventricular function, and recent-onset HF.43 Similarly, in another study by Lavie et al. on patients with systolic heart failure (HF), the role of cardiorespiratory fitness (CRF) was shown to influence survival outcomes significantly. The study revealed that individuals with low CRF exhibited higher annual mortality rates than those with high CRF, irrespective of body mass index (BMI). Notably, the obesity paradox—where overweight and obese patients have better prognoses—was evident only in the low CRF group. This suggests that CRF is a critical modifier of the obesity paradox in HF patients, emphasizing the importance of fitness over adiposity in predicting survival.44 Similarly, another study by Tutor A et al. has emphasized the role of cardiorespiratory fitness (CRF) in this paradox, suggesting that higher CRF levels may mitigate the adverse effects of obesity on cardiovascular outcomes.45 Exercise-based CR in CHD patients reduces cardiovascular mortality, cardiac events, and hospitalizations, while improving HRQoL and being cost-effective, even under contemporary medical management as shown by study conducted by To update and assess the impact of exercise-based cardiac rehabilitation (CR) in coronary heart disease (CHD) patients. A meta-analysis of 85 randomized controlled trials (RCTs) involving 23,430 participants with ≥6-month follow-up was conducted. Compared to no-exercise controls, CR significantly reduced cardiovascular mortality (RR 0.74), hospitalizations (RR 0.77), and myocardial infarction (RR 0.82). Improvements in health-related quality of life (HRQoL) and cost-effectiveness were noted. No significant benefit was observed for overall mortality or revascularization rates. Effects were consistent across different CHD subgroups and CR delivery models.46 In another study by McAuley et al. In this study of 9563 men with known or suspected coronary heart disease (CHD), cardiorespiratory fitness (CRF) was shown to modify the association between adiposity and mortality significantly. Over a mean follow-up of 13.4 years, low CRF was associated with increased all-cause and cardiovascular mortality across most BMI categories, especially in obese class II/III individuals. However, among men with high CRF, there were no significant differences in mortality regardless of adiposity measures such as BMI, waist circumference, or body fat percentage. These findings suggest that fitness is a stronger predictor of survival than fatness in CHD and should not be overlooked.47

Although obesity itself is considered to be a risk factor for the development of Chronic Kidney Disease (CKD), obesity paradox refers to an observation that obesity does provide survival benefit in advanced CKD.48, 49 As per CDC, during 2017- March 2020, the prevalence of obesity among US adults was 41.9 %. It was observed that compared to individuals without reduced eGFR 41.7 %, adults with reduced eGFR had greater prevalence of obesity 49.1 %.44 An advanced PubMed search was done using the keywords AND and around 24 articles were found that have discussed this particular topic in detail. Patients with advanced CKD i.e. with a glomerular filtration rate (GFR) of <30 and those with an End Stage Renal Disease (ESRD) who are on dialysis have a high annual mortality rate of 10 to 20 %, which is even higher that some common malignancies or cardiovascular conditions.45 From the available studies, one thing is certain that obesity is definitely associated with an increased incidence of CKD and loss of renal function and in a study including 3 million US veterans without a history of renal disease (GFR>60), it was found that adults with a BMI>30 were associated with a rapid loss of renal function.46 On the contrary, there is enough evidence to suggest that obesity was associated with better outcomes in CKD patients.50 CKD patients can be subdivided into advanced CKD (GFR<30), dialysis dependent, or renal transplant patients and data for obesity paradox differs across this. While meta-analyses done in the past suggest improved survival in predialysis advanced CKD and dialysis dependent CKD patients, however, analyses have shown poor outcomes in pretransplant obese patients.51,52 Retrospective cohort study done on 2852 NHANES participants from 1999–2006, showed protective association of high fat mass in CKD patients, particularly among patients with lower muscle mass.53 Cohort study conducted on 3605 Asian patients with CKD stages 1–5, who were divided into 6 groups depending on their BMI, showed low BMI was associated with poor renal outcome in all CKD stages, whereas high BMI was associated with poor renal outcome in CKD stages 1–3 but better renal outcome in CKD stage 4–5.54 The various mechanisms which can explain obesity paradox include Time-discrepancy between competing risk factors for death ( undernutrition vs overnutrition), reverse causation, survivor bias, alteration of circulating cytokines, favorable genetic variants/ expression, more stable hemodynamic status, endotoxin-lipoprotein interaction, uremic toxin sequestration and neurohormonal alterations.55 During these investigations, it was understood that CKD patients on long term dialysis had higher survival chances when they had a higher BMI arising from increased muscle mass.It was also concluded that higher body fat and BMI are associated with higher cardiovascular and all cause death rates in patients.56 Various weight loss strategies including surgical route have been tried but data was not consistent and did not offer any benefit as shown by a study by Choudhury et al. studied the outcome of obese CKD stage 3b patients with 3 different weight loss strategies including sleeve gastrectomy, Roux-en-Y gastric bypass and medical weight management, study showed that surgical interventions including sleeve gastrectomy and Roux-en-Y bypass only showed survival improvement in CKD stage 3b patients with class II and class III obesity, and not with class I obesity.57

Cancer is the second leading cause of death in the United States after heart disease. Obesity has long been considered a strong risk factor for cancer, however, recent studies have established an inverse relationship between obesity and cancer incidence and mortality, highlighting the existence of an 'obesity paradox' in the field of oncology. Emerging literature suggests that the relationship between BMI and cancer survival is U-shaped and that being overweight, may not increase risk and might even offer protection. A systematic review and metaanalyis done by Choi et al. in 2013 to examine association between BMI and Renal Cell Carcinoma (RCC) -specific survival among patients treated by nephrectomy found a statistically significant inverse association between high BMI and cancer-specific death (HR = 0.47; 95 % CI = 0.29 to 0.77) which also persisted after multivariable adjustment for stage, tumor size, grade, symptom presence, and baseline weight loss.58 Literature also highlights various genetic associations between obesity and its implicated survival in patients with these cancers. In a study done by Hakimi et al., they hypothesized that obese patients have downregulation of an oncogene overexpressed in many cancers, including clear cell RCC, called FASN (coding for fatty acid synthase) , which is also a rate limiting enzyme in fatty acid metabolism, a process essential for tumor growth. Another genetic association involves upregulation of an apoptotic protein TRAIL (TNF-related apoptosis-inducing ligand) in obese individuals which downregulates FASN, enzyme acetyl-CoA carboxylase, and GLUT-4 channels through the cleavage of caspase 3 and caspase 8.59,60 In addition, a 2017 study by Bette J. Caan revealed that the risk of colorectal cancer (CRC) is higher at both very low and very high BMI levels, showing a split effect.61 The most favorable outcomes were observed in individuals with average BMI, often falling within the overweight or Class 1 obesity categories, where the risk of CRC was 35 % lower compared to those with a normal BMI. Moreover, Wu et al., in their 2014 meta-analysis of 29 studies, found that BMI measured before, during, and after cancer treatment had different associations with patient outcomes.62 They observed that an increased pre-diagnosis BMI was linked to poor survival in patients with colorectal cancer (CRC), while post-treatment overweight was associated with better outcomes.63 A similar pattern was seen in the World Cancer Research Fund breast cancer report and across various studies.64,65 In the context of Non-Small Cell Lung Cancer (NSCLC), the 'Obesity Paradox' has also been observed. A 2016 study by Tatsuo Nakagawa demonstrated that obesity may be associated with a favorable prognosis and improved overall survival in patients with operable NSCLC.66 Earlier it was believed that obese patients would have more postoperative pulmonary complications after resection owing to decreased diaphragm excursion and lower lung volumes due to restriction, however this concept has been disproven as newer studies now show that patients who are underweight have more pulmonary and infectious complications. In a study done by Thomas et al., they categorized 19,635 patients into different categories based on their BMI- Overweight (25–30), Obese (>30) and revealed that patients who were overweight had lower mortality (OR: 0.72 p = 0.002) and obese patients had even more lower mortality (OR: 0.52 p < 0.001) compared to normal-weight patients and hence a statistically significant protective effect of obesity was observed.67 This comes with certain limitations, as BMI, the only readily available marker for overweight and obesity, cannot differentiate between fat and muscle mass. Additionally, disproportionate use of metformin (Glucophage), statins, as well as smoking has variable contributions in obese and non-obese patients.68 Another possible limitation is BMI measurement timing, as Lennon et al. highlighted. Understanding the reasons behind the obesity paradox is crucial for its application in clinical settings, underscoring the need for a framework to leverage obesity in cancer prevention effectively.5