Unsaturated fats may not always be anti-inflammatory, study finds

ISLAMABAD: Unsaturated fats, such as those found in oily fish, nuts, seeds, avocados, and olive oil, are recommended as part of a healthful diet.

Studies have linked these fatty acids to reduced levels of inflammation and lowered LDL (‘bad’) cholesterol. However, a new study suggests that both omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are linked to increased levels of some inflammatory markers in the blood.

Oily fish, nuts, seeds, avocados, and olive oil are all advocated as part of a healthful diet, mostly because of their high concentrations of unsaturated fatty acids. Studies suggest that unsaturated fatty acids, particularly omega-3Trusted Source, may reduce both inflammation, and levels of low-density lipoprotein, LDL or ‘bad’ cholesterol, which is linked to heart disease.

However, a new study has suggested that polyunsaturated fatty acids may actually increase levels of some inflammatory biomarkers in the blood plasma.

The research, which is published in The International Journal of Epidemiology, found that both omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) were associated with raised levels of glycoprotein acetyls (GlycA)Trusted Source, biomarkers associated with increased cardiovascular risk.

The researchers carried out their primary analysis on 2,802 participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, which recruited a total of 14, 541 pregnant women residing in southwest England in 1991 and 1992, and has followed them and their offspring since then. They replicated their analysis using data from 12,401 participants in the UK Biobank.

“Using two large datasets, ALSPAC and the UK Biobank, along with a genetic technique called Mendelian randomization, the researchers examined whether these fats cause changes in inflammation, rather than just being associated with it, exploring actual causality. This approach is especially powerful because it helps minimize the usual confounding factors found in nutrition studies, such as lifestyle or other dietary habits. In other words, the researchers went beyond asking who has more inflammation and what they eat and instead tried to determine whether the fats themselves were directly responsible.”

The researchers assessed the ALSPAC offspring after 24 years. In their analysis, they controlled for household social class at birth, maternal highest education qualification at birth, maternal and paternal smoking status during pregnancy, offspring sex at birth, type of drinker at age 24 , type of smoker at 24 , and at age in months at 24-year clinic.

Daisy Crick, corresponding author, Institute for Molecular Bioscience, Queensland University, Australia, and MRC Integrative Epidemiology Unit, The University of Queesland, Australia, explained their research:

“Dietary fatty acids were measured using levels of DHA, total omega-3 LA, total omega-6, and the omega-6:omega-3 ratio found in the blood. Inflammation was measured using substances in the blood called biomarkers and specifically we used the biomarkers C-reactive protein (CRP), Interleukin-6 (IL-6) and Glycoprotein Acetyls (GlycA).”

Can omega-3s be inflammatory? The researchers found that in both cohorts, both omega-3 and omega-6 levels were associated with higher levels of GlycA.

“Surprisingly, the results showed that both omega-3 and omega-6 fatty acids were associated with higher levels of a marker called GlycA (a novel inflammatory marker), which reflects low-grade chronic inflammation. This was unexpected, especially for omega-3s, which are widely promoted as anti-inflammatory.”

“Omega-3s are found in dark fatty fish, like salmon and sardines, and in plant-based foods like flaxseeds, chia seeds, and walnuts. Most people think of them as calming to the immune system. Yet in this study, higher omega-3 levels were linked to more inflammation, not less, at least when GlycA was used as the measurement,” he added. Omega-6 to omega-3 fatty acid ratio could be key In the ALSPAC cohort, there was a consistent association between a higher omega-6:omega-3 ratio and all three inflammatory biomarkers.

“This [finding] supports earlier findings that it’s not just about how much omega-3 you consume; it’s about how balanced your overall intake is. In fact, research highlights how this ratio has shifted dramatically in recent history. A century ago, people typically consumed a 4:1 ratio of omega-6 to omega-3. Today, due to modern diets rich in industrial seed oils, that ratio has ballooned to around 15:1 to 20:1. This shift creates a pro-inflammatory environment that could be contributing to chronic diseases, allergies, and autoimmune disorders.”

“Our findings suggest that it’s not as simple as ‘omega-3 is anti-inflammatory, and omega-6 is pro-inflammatory’. Just increasing the consumption of omega-3 through diet or supplements might not be enough to lower inflammation. Instead, our results suggest that it might be more useful to look at the balance or ratio between omega-6 and omega-3 in the diet. Improving the balance between the two fats could be a better method for people who want to reduce inflammation in their bodies.”

Although the study found an association between PUFAs and some of the 3 biomarkers, the authors emphasize that different biomarkers measure different aspects of inflammation, so by assessing only 3 biomarkers, they may have missed some important effects of PUFAs on inflammation. Further research using additional biomarkers is needed to better understand the relationship between PUFAs and inflammation.

“It is important to remember that the study measured just three inflammatory markers. The immune system is incredibly complex, and omega fatty acids might influence other pathways that weren’t captured here. For example, omega-3s might still help resolve short-term inflammation or protect against specific diseases, even if they raise GlycA slightly. More research using a broader range of immune biomarkers will help clarify this relationship.”

Despite this limitation, the findings highlight that there may be more to the relationship between fatty acids and health than previously thought.

“The relationship between fatty acids and inflammation is complex and our findings only tell part of the story. Although we show that omega-3 fats are associated with increases in some biomarkers of inflammation, it does not rule out other potential beneficial effects of these fatty acids in the diet.”