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

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

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

A study recently published in the journalNutrientsTo non-agenarians from Sardinia's Blue Zone called for conventional wisdom. It has been shown that people with moderate hypercholesterolemia (LDL-C ≥130 mg/dl) can have a longer lifespan. However, this effect was not observed in people with very high cholesterol levels, particularly women. By studying the cholesterol profiles of a long-lived population, the team of Italian researchers aimed to determine whether high cholesterol levels represented a risk or a hidden benefit.

Hypercholesterolemia

For decades, high cholesterol has been linked to an increased risk of cardiovascular disease, a leading cause of death worldwide. Medical guidelines have long emphasized the importance of reducing cholesterol levels and preventing 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 indicating that higher cholesterol levels may be associated with lower mortality rates in older individuals. Some researchers argue that this is due to reverse causality - whereby falling cholesterol levels are a result rather than a cause of worsening health. The Sardinian study eliminated this possibility by excluding participants with severe illness or poor self-rated health, but found a link 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.

Examining the cholesterol paradox

Physical activity played a key role - the study found that 85.2% of men and 69.0% of women exercised at least three times a week, suggesting that lifestyle factors may contribute to the cholesterol paradox.

The researchers examined cholesterol levels in one of the longest-living populations in the world: 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 over 90 live.

The team selected 168 nonagenarians (81 men and 87 women) from this population in 2018 and tracked their health until December 2024, at which point the 20 participants were still alive. To ensure the accuracy of their results, the study only included people with all four grandparents born in the blue zone.

Lipid profiles were measured using standard blood tests after a quick overnight stay and serum cholesterol levels - including total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides were analyzed according to established medical guidelines. Participants were divided into two groups based on a threshold of 130 mg/dL 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 analyzes using various regression models to determine the association between cholesterol levels and longevity.

To reduce confounding factors, people taking both cholesterol-lowering medications and loop diuretics were also excluded from the study. In addition, the researchers took factors such as gender, high blood pressure and general health into account in their analysis. However, the study only measured cholesterol levels at baseline and did not track long-term cholesterol trends over the participants' lifetime.

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Key insights

Dietary habits matter - The study found a significant positive correlation between LDL cholesterol levels and grain consumption, while olive oil intake was associated with lower non-HDL cholesterol levels.

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

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 individuals with normal cholesterol levels. This finding remained significant even after adjusting for potential confounding factors such as gender, 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 had no additional survival benefit, and in women, very high cholesterol levels were associated with shorter survival.

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

Genetic resilience may be a factor - researchers believe historical exposure to malaria in Sardinia may have favored genetic traits that allow high cholesterol without increased risk of heart disease.

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

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

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

Conclusions

Cholesterol-lowering drugs may need to be reconsidered—researchers have questioned whether statin use is beneficial or necessary in very old adults because lowering cholesterol may not always improve survival in this population.

Overall, the results suggest that the popular belief that lower cholesterol is always better may not apply to individuals in their 90s. Instead, moderate hypercholesterolemia may be a marker of resilience in aging populations.

While these results do not suggest abandoning cholesterol management altogether, they do demonstrate the need for more nuanced, age-specific approaches to cardiovascular health. The study found that future research should examine 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 the long-lived Sardinian population. One hypothesis is that historical exposure to malaria has selected for individuals with naturally higher cholesterol levels, which may provide some immune benefits without increasing cardiovascular risk.

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

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