Linoleic acid has long been celebrated for its potential cardiovascular benefits due to its low-density lipoprotein (LDL cholesterol) lowering properties. However, the whole body of research shows that linoleic acid is not heart-healthy as it was once previously believed.

Instead, intake of linoleic acid, particularly in the context of an imbalanced omega-6 to omega-3 fatty acid ratio, contributes to the development and progression of cardiovascular disease.

One of the primary concerns surrounding linoleic acid is its role in promoting inflammation, a key driver of atherosclerosis and other cardiovascular conditions. While linoleic acid can lower LDL cholesterol, it also increases the production of pro-inflammatory eicosanoids when metabolized.

The impact of linoleic acid on cardiovascular health is heavily influenced by the dietary n-6/n-3 fatty acid ratio. A high intake of linoleic acid, relative to omega-3 fatty acids, is associated with an increased risk of atherosclerosis.

This is primarily due to the pro-inflammatory nature of linoleic acid when omega-3 intake is insufficient to counterbalance the production of inflammatory mediators. The modern Western diet, characterized by an overwhelming predominance of omega-6 fatty acids, exacerbates this issue, increasing the prevalence of cardiovascular disease.

Oxidized Low-density Lipoprotein (oxLDL)

The causal link between linoleic acid and oxidized low-density lipoprotein (oxLDL) further implicates linoleic acid in the pathogenesis of cardiovascular disease.

Without oxLDL atherosclerotic plaque formation does not happen, and studies have shown that diets high in linoleic acid lead to elevated levels of oxLDL. There is a strong link between circulating oxLDL and the risk of atherosclerotic cardiovascular disease, suggesting that linoleic acid’s role in elevating oxLDL levels is the key mechanism through which it promotes cardiovascular disease

Fundamentally, linoleic acid causes LDL Cholesterol to become oxLDL through two key mechanisms.

Firstly, when linoleic in the diet is increased the composition of LDL Cholesterol changes to incorporate more of this unstable fatty acid, making the LDL particle more susceptible to oxidation.

Secondly, dietary linoleic acid is the primary driver of oxidative stress in the human body in a western context. So not only does linoleic acid make LDL particles weaker and more susceptible to oxidation, it then creates an environment of increased oxidative stress which oxidizes the LDL particle.

Lp-PLA2

Clinical studies also highlight the adverse effects of linoleic acid on cardiovascular health. For example, Scientists found that an 8-week intake of linoleic acid-rich soybean oil significantly increased Lp-PLA2 activity, an inflammatory marker associated with cardiovascular events, in healthy adults. This finding is particularly concerning, as it suggests that even in the absence of overt cardiovascular disease, high linoleic acid intake can predispose individuals to inflammation and subsequent cardiovascular complications.

Linoleic Acid’s Interaction With Other Fats

The complexity of linoleic acid’s impact on cardiovascular health is further underscored by its interaction with other dietary fats. For instance while linoleic acid lowers LDL cholesterol, this is outweighed by its pro-inflammatory effects when consumed in a diet low in omega-3 fatty acids or high in saturated fats.

Specifically, saturated fat, found in abundance in nature and historical human diets, is inert if not beneficial in the absence of linoleic acid. It is only when linoleic is introduced into the diet that this fat contributes to pathogenesis.

Human Trials

We are always cautious to discuss human trials for 2 reasons.

Firstly it takes at least 8 years to remove a significant amount of linoleic acid from your body so any modern study needs to have a washout period of at least 8 years at the start (impossible).

Secondly, the only place to find modernized subjects who do not require a washout is pre-1980, and the studies conducted then has some questionable controls. That said, the human trials conducted pre-1980 do show that increased linoleic acid diets lead to an increase in cardiovascular disease.

The Sydney Diet Heart Study, a randomized controlled trial conducted between 1966 and 1973, examined the effects of increasing linoleic acid intake by substituting safflower oil (which is about 75% linoleic acid) for saturated fats from sources like animal fats, margarines, and shortenings.

The study compared this intervention with a control group that received no specific dietary guidance. The findings revealed that 17.6% of participants in the safflower oil group died, compared to 11.8% in the control group, representing a 62% higher relative risk of death. 

Additionally, 17.2% of those in the safflower oil group died from cardiovascular disease, versus 11% in the control group, indicating a 70% increase in the relative risk of death from cardiovascular disease.

The Minnesota Coronary Experiment was a randomized, double-blind clinical trial involving more than 9,000 men and women that ran between 1968 and 1973.

The study compared a control diet containing 5% omega-6 polyunsaturated fatty acids with another diet that had three times the amount of omega-6, primarily sourced from trans fat-rich margarine and seed oils. Participants on the 15% omega-6 diet experienced a reduction in cholesterol levels.

The study’s data revealed that 41% of individuals in the seed oil group had at least one heart attack, compared to 22% in the control group.

In light of this evidence, it is essential to reconsider the role of linoleic acid in cardiovascular disease prevention. The current dietary guidelines, which promote linoleic acid-rich oils as heart-healthy, need to be revised to reflect the risks associated with linoleic acid intake. 

Reducing the intake of omega-6-rich oils is a more effective strategy for preventing cardiovascular disease. The mechanisms in which linoleic acid leads to marked increases in oxLDL alone can justify the position that linoleic acid causes cardiovascular disease.