A recent study published in the journal Nutrients has challenged long-standing perceptions about cholesterol and longevity. Conducted among nonagenarians in Sardinia’s Blue Zone, the research suggests that moderate hypercholesterolemia (where LDL-C is equal to or more than 130 mg/dL) may be associated with longer lifespans. However, this potential protective effect was not observed in individuals with excessively high cholesterol levels, particularly among women.For decades, medical guidelines have emphasised the need to lower cholesterol levels to reduce cardiovascular disease risk. However, emerging evidence indicates that the relationship between cholesterol and health outcomes may be more nuanced, particularly in older populations. The Sardinian study, led by a team of Italian researchers, examined whether higher cholesterol levels could act as a marker of resilience in aging populations.Known as the 'cholesterol paradox,' the phenomenon describes findings that indicate higher cholesterol levels may correlate with lower mortality rates in elderly populations. Some experts believe this could result from reverse causality, where declining cholesterol levels are a consequence of poor health rather than a cause. In this study, the researchers controlled for this by excluding participants with severe illnesses or poor self-rated health, yet the association between higher LDL-C and longer survival remained.The study focused on a cohort of 168 nonagenarians (81 men and 87 women) from Sardinia’s Blue Zone, a region renowned for its unusually high number of long-lived residents. Data collection began in 2018 and continued until December 2024, during which 20 participants remained alive. To ensure the accuracy of their findings, the study included only those whose four grandparents were born within the Blue Zone, thereby reducing genetic variability.Researchers assessed lipid profiles using blood samples collected after an overnight fast. Serum cholesterol levels, including total cholesterol, LDL, HDL, and triglycerides, were measured according to established guidelines. Participants were then categorized based on LDL-C levels, with a threshold of 130 mg/dL separating those with moderate hypercholesterolemia from those with lower levels.The findings indicated that those with LDL-C levels above 130 mg/dL had a significantly longer median survival of 3.82 years, compared to 2.79 years among those with lower LDL-C levels. Statistical analysis revealed that moderate hypercholesterolemia was associated with a 40% lower mortality risk, even after accounting for factors such as sex, smoking status, and comorbidities. Interestingly, however, total cholesterol levels above 250 mg/dL did not confer additional survival benefits and were linked to shorter lifespans in women.The study also highlighted lifestyle factors that may influence the cholesterol paradox. Over 85% of male participants and 69% of female participants reported engaging in physical activity at least three times per week, suggesting that exercise may play a role in mitigating the risks associated with elevated cholesterol levels.Moreover, dietary habits emerged as another potential factor. Participants with higher LDL-C levels reported greater cereal consumption, while those with lower non-HDL cholesterol levels consumed more olive oil. However, the study did not assess dietary intake over time, making it difficult to draw definitive conclusions about diet’s role in the observed associations.While these findings suggest that moderate hypercholesterolemia may not be as detrimental for very old individuals as previously thought, the researchers emphasized that the study’s limitations warrant caution. The relatively small sample size, single-point cholesterol measurement, and focus on a genetically unique population mean that the results may not be generalizable to other groups.Nevertheless, the study raises important questions about current cholesterol management guidelines for older adults. As life expectancy continues to rise, it may be necessary to adopt more individualized approaches to cardiovascular health, considering not just cholesterol levels but also genetic, dietary, and lifestyle factors.