Higher 'bad' cholesterol levels may help Sardinia’s seniors live longer, study finds

By Dr. Chinta SidharthanReviewed by Susha Cheriyedath, M.Sc.Feb 24 2025

A new study of Sardinia’s longest-living residents reveals that moderate LDL cholesterol levels may be a secret to longevity—challenging mainstream medical advice on cholesterol management.

Study: The Cholesterol Paradox in Long-Livers from a Sardinia Longevity Hot Spot (Blue Zone). ​​​​​​​Image Credit: Naeblys / Shutterstock

A recent study published in the journal Nutrients on nonagenarians from Sardinia’s Blue Zone challenged conventional wisdom. It revealed that individuals with moderate hypercholesterolemia (LDL-C ≥130 mg/dL) may have longer lifespans. However, this effect was not observed in individuals with very high cholesterol levels, particularly women. By examining the cholesterol profiles of a long-lived population, the team of Italian researchers aimed to determine whether high cholesterol levels are a risk or a hidden advantage.

Hypercholesterolemia

For decades, high cholesterol has been associated with an increased risk of cardiovascular disease, one of the leading causes of death worldwide. Medical guidelines have long emphasized the importance of lowering cholesterol levels to prevent heart attacks and strokes. However, recent studies suggest a more complex relationship between cholesterol and longevity, particularly in older populations.

The "cholesterol paradox" refers to findings that indicate higher cholesterol levels may be linked to lower mortality rates in elderly individuals. Some researchers argue this is due to reverse causality—where declining cholesterol is a result, rather than a cause, of worsening health. The Sardinian study accounted for this possibility by excluding participants with severe illnesses or poor self-rated health, yet still found an association between higher LDL-C and longer survival. Others believe cholesterol may play a protective role in aging by supporting immune function and cellular repair. Despite these debates, the relationship between cholesterol and survival remains unclear.

Investigating the cholesterol paradox

The researchers examined the cholesterol levels in one of the world’s longest-living populations: the elderly residents of Sardinia’s Blue Zone. The study was conducted in a region in central Sardinia, Italy, where a large number of people live past 90.

The team selected 168 nonagenarians (81 men and 87 women) from this population in 2018 and followed their health status until December 2024, at which point 20 participants were still alive. To ensure the accuracy of their findings, the study only included individuals with all four grandparents born within the Blue Zone.

Lipid profiles were measured using standard blood tests after an overnight fast, and serum cholesterol levels—including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides—were analyzed following established medical guidelines. The participants were divided into two groups based on a threshold of 130 mg/dL of LDL-C.

The study also collected extensive lifestyle and health data, including diet, physical activity, smoking status, comorbidities, and self-rated health. The researchers conducted statistical analyses using various regression models to determine the association between cholesterol levels and longevity.

Furthermore, to reduce confounding factors, individuals taking both cholesterol-lowering medications and loop diuretics were excluded from the study. Additionally, the researchers accounted for factors such as sex, hypertension, and overall health status in their analysis. However, the study measured cholesterol only at baseline and did not track long-term cholesterol trends over the participants’ lifetimes.

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Major findings

The study found that moderate LDL cholesterol levels (≥130 mg/dL but below extreme levels) were associated with longer survival among the nonagenarians studied. Participants with LDL-C levels above 130 mg/dL had a significantly longer median survival (3.82 years) than those with LDL-C levels below this threshold (2.79 years).

The regression analysis also confirmed that individuals with moderate hypercholesterolemia, with LDL-C levels ≥130 mg/dL, had a 40% lower risk of mortality compared to those with normal cholesterol levels. This finding remained significant even after adjusting for potential confounding factors such as sex, smoking status, and comorbidities.

However, the study did not find a simple linear relationship between cholesterol and longevity. Participants with total cholesterol levels above 250 mg/dL did not experience additional survival benefits, and in women, very high cholesterol was linked to shorter survival.

These results challenged the prevailing assumption that lower cholesterol is always beneficial for longevity. Instead, they suggested that higher cholesterol levels in very old individuals might not be inherently harmful and could, in some cases, have protective effects. Some researchers speculate that cholesterol might support immune function, reduce the risk of infections, and contribute to cellular maintenance, all of which are crucial in aging populations.

However, the study had various limitations. The relatively small sample size could affect the generalizability of the results. Additionally, cholesterol levels were measured only at baseline, meaning that the researchers could not assess long-term cholesterol trends over the participants’ lifetimes. Another limitation is that most participants were on antihypertensive therapy, making it difficult to determine whether blood pressure control influenced survival outcomes.

The study also explored potential dietary influences on cholesterol levels. It found that higher LDL-C levels correlated with greater cereals consumption, while olive oil intake was associated with lower non-HDL cholesterol. However, the role of diet in the cholesterol paradox remains unclear and requires further research.

Despite these limitations, the study adds to a growing body of evidence suggesting that cholesterol management guidelines may need reconsideration for older adults. The findings raise the question of whether cholesterol-lowering treatments are beneficial for individuals over 90 or whether such interventions might be unnecessary—or even harmful—in some cases.

Conclusions

Overall, the findings suggested that the widely held belief that lower cholesterol is always better may not apply to individuals in their 90s. Instead, moderate hypercholesterolemia might be a marker of resilience in aging populations.

While these results do not suggest abandoning cholesterol management altogether, they do highlight the need for more nuanced, age-specific approaches to cardiovascular health. The study indicated that future research should explore whether cholesterol-lowering treatments benefit or potentially harm aging individuals.

The authors also speculated that genetic and environmental factors may contribute to the cholesterol paradox in Sardinia’s long-lived population. One hypothesis is that historical exposure to malaria may have selected for individuals with naturally higher cholesterol levels, which could offer some immune advantages while not increasing cardiovascular risk.

As research continues, the study underscores the importance of personalizing medical guidelines rather than applying one-size-fits-all recommendations across all age groups.