Depression is a complex and chronic mental disorder that is characterized by low mood, loss of interest, slowed thinking, poor eating and sleeping (Park et al., 2019). According to the World Health Organization (WHO), >350 million people worldwide suffer from depression (Kuehn, 2020). By 2030, depression is predicted to become the leading disease with the highest global burden of disease (Marwaha et al., 2023). However, the causes of depression are still not fully understood, and a definitive cure remains unavailable. Current research suggests that depression is a multifactorial disorder influenced by genetics, environment and nutrition (Marwaha et al., 2023). Dietary fatty acids, an important nutrient in the diet, have been believed to be linked to depression due to their specific characteristics. Research has shown that unsaturated fatty acid deficiencies reduce serotonin function and dopamine activity in the frontal cortex on the left side (Patrick and Ames, 2015). Moreover, excess saturated fats can trigger chronic inflammation, which can reduce serotonin and frontal cortex activity and ultimately worsen depression. Omega-3 polyunsaturated fats, known for their anti-inflammatory properties, have been found to be inversely associated with depression in older adults (Lai et al., 2016). On the other hand, higher intake of total dietary fat and saturated fat has been positively associated with depression (Lai et al., 2016). In addition, during an 8-week period of feeding Sprague-Dawley (SD) rats various high-fat diets (lard, saturated fat, and olive oil, unsaturated fat), both the lard and olive oil groups exhibited weight gain. However, anxiety-depressive behaviors were observed specifically in the lard group and not in the olive oil group (Nakajima et al., 2019). Short-chain fatty acids (such as propionic acid and butyric acid) were also found to be lower in depressed people in a small population study of 117 women (Skonieczna-Żydecka et al., 2018). Taken as a whole, these studies suggest that different types of fatty acids may have different effects on depression. However, the fatty acids in these studies were all saturated or saturated with <20 carbons. There is still a lack of research on the relationship between very long chain saturated fatty acids (VLSFAs) and depression in neither human nor animal study.

VLSFAs are saturated fatty acids that contain 20 or more carbons (Lemaitre et al., 2015). Due to the difficulty in assessing total dietary FFA intake, most studies focused on circulating VLSFAs levels, an objective indicator of combined diet and metabolism. Circulating VLSFAs originate both from the dietary and endogenous synthesis. VLSFA are present in some foods, such as peanuts, macadamia nuts, cashews, canola oil, and other nuts and oils (Lemaitre et al., 2015). Studies have shown that circulating VLSFAs levels can be increased through short-term feeding trials of peanuts and macadamia nuts (Garg et al., 2003; Lam et al., 2012). It can also be synthesized in the endoplasmic reticulum by elongation of 16:0 and 18:0 in the presence of enzymes of the elongation of very long chain fatty acids (ELOVL) family (Sassa and Kihara, 2014). Recent studies have found a clear correlation between high levels of circulating VLSFAs and a lower risk of heart disease and type 2 diabetes (Fretts et al., 2019; Lemaitre et al., 2018), as well as lower mortality (McBurney et al., 2021). In addition, a higher proportion of VLSFAs in the plasma was found to be protective against cognitive decline in the Atherosclerosis Risk in Communities (ARIC) cohort (D. Li et al., 2020). These studies suggest that the association of circulating saturated fatty acids with health risks may vary depending on the length of the saturated fatty acid chain and VLSFAs may play a protective role in many health problems.

Here, we conducted this study to examine the association between circulating VLSFAs and depression using survey data from the 2011–2014 National Health and Nutrition Examination Survey.