Cardiovascular diseases (CVD) are the primary cause of mortality worldwide (1). Numerous risk factors including smoking, dyslipidemia, hypertension, obesity, lack of physical activity, and ethnicity are closely associated with CVD (1). It is noteworthy that behavioral risk factors could prevent up to 90% of CVD incidents (2). Additionally, dietary habits and specific dietary components significantly influence CVD (3). LA, a crucial fatty acid that must be ingested through diet sources like vegetable and nut oils, poultry, meat, eggs, milk, and margarine, cannot be synthesized by humans (4, 5). AA, derived from LA, is also a key PUFA (6, 7).

Growing research highlights the potential impact of omega-6 PUFAs on reducing CVD risk (8–10). For instance, a meta-analysis found that higher LA levels in the body were linked to a reduced risk of coronary heart disease (CHD) (11). However, no significant association was found between AA levels and CHD risk (8). Another analysis demonstrated that increasing dietary LA by 5% of total energy, substituting saturated fats, correlated with a 9% reduction in CHD incidents (9). A comprehensive analysis from 11 studies indicated that omega-6 PUFAs were associated with a decrease in both CHD events and mortality, showing hazard ratios of 0.87 and 0.74, respectively (8). Another study showed replacing saturated fats with omega-6 PUFAs significantly cut total cholesterol by 19%, LDL-C by 22%, and increased HDL-C by 14% among nutrition students (9). Further, each 5% replacement of saturated fats with PUFAs reduced LDL-C by 10 mg/dL and the TC ratio by 0.16 (12).

Despite these findings, some studies offer mixed results. The Sydney Diet Heart Study, an RCT with 458 middle-aged men with recent coronary events, reported increased mortality rates when replacing saturated fats with LA (13). Additionally, comprehensive reviews have found no definitive links between omega-6 PUFA intake and CVD outcomes (14, 15). It is suggested that diets high in omega-6 PUFAs might elevate proinflammatory mediators like prostaglandins and leukotrienes, which could adversely affect CVD risk (4, 16).

The limitations of individual studies, including small sample sizes, variations in research design, and diverse participant profiles, underline the need for broader investigations. This study utilized the 2021 Global Burden of Disease data to explore the effects of a diet low in omega-6 PUFAs on CVD. Moreover, future CVD trends were predicted using the ARIMA model, validated by previous research (17, 18).

This investigation assessed the global consequences of cardiovascular disease (CVD) linked to diets deficient in omega-6 polyunsaturated fatty acids over the period from 1990 to 2021, identifying a significant decline. The most impacted demographic was males over the age of 75, who displayed elevated incidence rates. Projections for the future indicate a likely reduction in mortality rates in regions with higher social development index (SDI) scores, although high mortality and age-standardized death rates from such diets are expected to continue in Russia and the North Africa and Middle East region. This study represents the first extensive review of CVD effects stemming from insufficient intake of omega-6 polyunsaturated fatty acids.

Prior analyses, including a meta-analysis of 25 case-control studies, found a negative correlation between levels of linoleic acid (LA) in blood and tissues and coronary heart disease (CHD) risk (8). While arachidonic acid (AA) was not significantly linked to CHD risk, lower levels of AA in adipose tissue were tied to increased CHD event risk in longitudinal studies, yet were associated with a reduced risk in cross-sectional analyses (8). A different meta-analysis covering 13 cohort studies involving 30,602 subjects (with 12,479 CHD events, including 5,882 fatalities) highlighted the protective effects of increased LA intake against CHD occurrences and mortality, indicating that substituting saturated fats with LA could lower CHD event and death risks by 9 and 13%, respectively (9). Earlier analyses, including 60 clinical trials (33), and another encompassing 8 randomized control trials (RCTs) with 13,614 participants experiencing 1,042 CHD events (12), noted that omega-6 PUFAs positively influenced blood lipids and reduced CHD events. Moreover, a Cochrane review of dietary fat modifications through RCTs indicated that substituting saturated fats with monounsaturated or polyunsaturated fatty acids modestly but effectively decreased CVD risk over a minimum of 6 months (34).

A study of 1,551 middle-aged men explored the impact of dietary LA and total PUFA consumption on CVD mortality, revealing an inverse relationship with CVD deaths (35). A systematic review of 19 studies including 6,461 adults (average age: 50 years) suggested minimal effects on mortality or CVD events over 1–8 years by increasing omega-6 PUFA intake, though it could potentially lower heart attack risks (36). Omega-6 PUFAs were found to reduce serum total cholesterol (TC) by 6%, without significant changes to triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). It is important to note that limited event numbers and the underrepresentation of participants from developing countries and women may have affected these findings (13).

Additional cohort research indicates that a diet low in saturated fatty acids and enriched with omega-6 PUFAs correlates with decreased CHD risk and lower levels of LDL-C (10, 11). Jakobsen et al. (11) demonstrated that substituting carbohydrates with PUFAs (omega-6) can reduce levels of TC, HDL-C, LDL-C, and TG. However, the validity of these findings is limited due to the short duration of interventions and the inclusion of non-randomized studies, which may undermine their clinical relevance (34).

The impact of omega-6 PUFAs on CVD risk remains debated. While some studies support the positive effects of omega-6 PUFA supplementation on cardiovascular outcomes, contrasting studies present divergent results. A potential explanation for the complex relationship between omega-6 PUFAs and CVD risk involves the enhanced synthesis of 2-series prostaglandins and 4-series leukotrienes, which are proinflammatory and may adversely influence residual CVD risk (4, 16). Furthermore, compounds like AA, a highly unsaturated fatty acid, could increase LDL-C and VLDL oxidation, elevating their atherogenic potential (4). Conversely, certain investigations show no correlation between omega-6 PUFA consumption and CVD risk, including a 14-year longitudinal study involving 43,732 men which found no link between overall fat consumption, cholesterol, and stroke risk (37). Additionally, an analysis of prospective observational studies and RCTs indicated that high PUFA intake coupled with low saturated fat intake did not significantly alter CVD outcomes (15). Likewise, a Cochrane review involving 660 participants detected no significant connections between varying omega-6 PUFA intake levels and CVD risk factors (14). Furthermore, another systematic review concluded that replacing saturated fats with cis-PUFAs, akin to omega-6 PUFAs, markedly reduced TC, supporting findings of our current study (38–46).

Previously, another study analyzes the global impact of nonoptimal dietary fat intake on coronary heart disease (CHD) mortality, highlighting the health burden linked to low ω-6 polyunsaturated fat (PUFA) intake and high saturated (SFA) and trans fats (TFA) consumption. It reveals significant disparities in CHD mortality, particularly in countries with poor dietary management and lower socioeconomic status. Targeted public health interventions, such as promoting ω-6-rich foods and reducing SFA and TFA intake, could substantially lower CHD rates, especially in high-risk regions. Additionally, regional variations indicate that global dietary guidelines should be tailored to local nutritional contexts. The study underscores the effectiveness of past interventions while revealing ongoing challenges in food policy. Ultimately, it provides a vital evidence base for future public health strategies to combat diet-related CHD worldwide. Future research should continue to track these trends and evaluate the impact of targeted dietary interventions (33).

Firstly, the variability in results could be attributed to the heterogeneity in dietary sources and the composition of omega-6 PUFAs in different studies. For example, arachidonic acid (AA), a type of omega-6 PUFA, has been shown in some studies to promote inflammatory processes that could exacerbate CVD risks. In contrast, linoleic acid (LA), another omega-6 PUFA, is often associated with protective effects against CVD. This discrepancy suggests that not all omega-6 PUFAs uniformly affect CVD risk, and their impact could be context-dependent based on their specific biochemical pathways and interactions within the body.

Secondly, the methodological differences across studies, such as the duration of follow-up, the age and baseline health conditions of participants, and how dietary intake was assessed, can also lead to conflicting results. Longitudinal studies might capture more reliable effects of long-term dietary patterns, whereas cross-sectional studies may not adequately reflect the chronic nature of dietary impacts on cardiovascular health.

Furthermore, genetic factors could play a significant role in modulating the effects of omega-6 PUFAs on CVD risk. Individual genetic variability in fatty acid metabolism might influence how these fats affect the individual’s risk profile. This aspect is often not fully accounted for in many studies, leading to an incomplete picture.

To enhance the credibility and depth of our discussion on this topic, future research should aim to standardize the types of omega-6 PUFAs studied and consider a more detailed analysis of the genetic and metabolic contexts of study populations. Additionally, more rigorous control of dietary assessment methods and a comprehensive evaluation of inflammatory markers could provide clearer insights into the pathways through which omega-6 PUFAs influence CVD risk. Addressing these complexities in a detailed manner would not only resolve the existing controversies but also significantly advance our understanding of the nutritional management of cardiovascular health.

This study has several limitations. First, the time frame of the data used primarily comes from the Global Burden of Disease (GBD) database, which provides epidemiological information for the selected period but does not adequately reflect the latest trends in dietary habits and public health interventions. This may impact the generalizability of the findings. Second, the study lacks data on genetic susceptibility and lifestyle factors (such as physical activity, smoking, and psychological stress), limiting our ability to explore the potential effects of these variables on cardiovascular disease risk. Finally, the analysis does not delve into the molecular mechanisms by which omega-6 polyunsaturated fatty acids (PUFAs) influence cardiovascular disease, restricting our understanding of the mechanisms of action and preventing the formulation of new intervention strategies.

Besides, a notable limitation is the inconsistent data quality and accessibility from less developed areas, particularly Sub-Saharan Africa. Relying on mathematical models to estimate CVD burdens in these regions introduces considerable uncertainty. Moreover, while the study spans from 1990 to 2021, offering a long-term overview, it may not capture the latest dietary shifts or the impact of recent public health initiatives, potentially skewing the study’s findings. This temporal limitation indicates that the latest changes in dietary habits and health policies might not be accurately reflected in the study’s outcomes.

This study thoroughly analyzes the global influence of cardiovascular disease (CVD) connected to insufficient intake of omega-6 polyunsaturated fatty acids from 1990 to 2021, highlighting a significant decrease over the period. The group most impacted included seniors above the age of 75, with men experiencing a particularly high incidence. Predictions suggest that areas with high socio-demographic index (SDI) values could see decreases in mortality, DALY rates, ASMR, and ASDR in the future. At the national level, places like Russia and regions in North Africa and the Middle East are expected to continue experiencing substantial CVD burdens linked to diets deficient in omega-6 polyunsaturated fatty acids through 2030 and 2050.

These insights are vital for developing CVD prevention tactics and underline the need to regulate dietary patterns.