Omega-3 and omega-6 are two types of polyunsaturated fatty acids. They are both required for the body to function but have opposite effects when it comes to the inflammatory response and cardiovascular health. Too much omega-6 and too little omega-3 are among the causes for many diseases in modern society.
Fat is perhaps the most diverse class of dietary macronutrients in regards to nutritional value and physiological effects. Currently, most people understand the differences between the good (unsaturated fat), bad (saturated fat) and ugly (trans-fat) fats described in Fat Metabolism 101. We know that oils derived from animal fat are not good for our health due to their high levels of saturated fat and cholesterol, and that oils derived from plants are generally good for our health due to their unsaturated fat content. However, not all unsaturated fats are healthy. Many plant seed oils such as sunflower, peanut and corn oil are rich in inflammatory polyunsaturated fatty acids (PUFAs) and devoid of anti-inflammatory PUFAs. On the other hand, some plant seed oils such as canola and olive oil have balanced PUFAs and are considered healthier. Therefore, it is important to distinguish between the types of PUFAs in dietary oils for optimal health.
PUFAs are fatty acids that have two or more double bonds in each molecule. There are two types of PUFAs in dietary oil: omega-3 and omega-6, also known as ω-3 and ω-6. They are distinguished by the position of the first double bond. Omega-3 fatty acids have their first double bond at the third carbon atom from the methyl end of the carbon chain while omega-6 fatty acids have their first double bond at the sixth carbon atom from the methyl end (Fig.1).
The most common omega-3 fatty acids in the human diet are ALA, EPA, and DHA while the most common omega-6 fatty acids are LA and AA (Table 1). The omega-3 fatty acid ALA and the omega-6 fatty acid LA are referred to as essential fatty acids because the body cannot synthesize them. Essential fatty acid deficiency can lead to dermatitis, stunted growth in infants and children, increased susceptibility to infection, and poor wound healing. In human cells all long-chain omega-3 fatty acids are synthesized from ALA and all long-chain omega-6 fatty acids are synthesized from LA.
|Types||Abbreviation||Common Name||Structure||Dietary Sources|
|Omega-3||ALA||α-Linolenic acid||C18 : 3||Oils: flaxseed, olive, canola|
|EPA||Eicosapentaenoic acid||C20 : 5||Fish oil, marine algae|
|DHA||Docosahexaenoic acid||C22 : 6||Fish oil, marine algae|
|Omega-6||LA||Linoleic acid||C18 : 2|| Oils: corn, soybean,
|AA||Arachidonic acid||C20 : 4|| Small amount in meat,
dairy products and eggs
Long-chain omega-3 fatty acids (EPA and DHA) provide many health benefits with regard to their cardiovascular disease prevention properties and anti-inflammatory effects. DHA is also directly involved in visual and neuronal cell development. Adequate amounts of omega-6 fatty acids are also beneficial to human health since many bioactive signaling molecules, especially ones involved in immune response and cardiomyocyte (muscle cells) contraction, are derived from them. However, omega-6 fatty acids tend to be over-supplied while omega-3 fatty acids are under-supplied in modern Western diets due to industrialized food oil production. This overwhelming intake of omega-6 leads to hyperimmune responses and interferes with the proper function of omega-3 fatty acids, causing detrimental effects associated with chronic cardiovascular diseases and inflammatory responses (Table 2).
|Chronic Diseases||Risk Factors||Comments||Omega-3||Omega-6|
|Arrhythmias (irregular heart beat)||Causes sudden cardiac death||Lowers||Increases|
|Thrombosis (clot)||Leads to myocardial infarction or stroke||Lowers||Increases|
|Atherosclerotic plaque||Leads to atherosclerosis||Lowers||Increases|
|Triglycerides||Cardiovascular risk factor||Lowers||Increases|
|IL-1 (Interleukin 1)||Inflammation response||Lowers||Increases|
|IL-6 (Interleukin 6)||Inflammation response||Lowers||Increases|
|CRP (C-reactive protein)||Inflammation response||Lowers||Increases|
Due to the opposing effects of omega-3 and omega-6 fatty acids, a healthy diet should contain a balanced omega-6:omega-3 ratio. Human beings evolved eating a diet with a omega-6:omega-3 ratio of about 1:1. Modern Western diets exhibit omega-6:omega-3 ratios ranging between 15:1 to 17:1. Epidemiology and dietary intervention studies have concluded that while an exceptionally high omega-6:omega-3 ratio promotes the development of many chronic diseases, a reduced omega-6:omega-3 ratio can prevent or reverse these diseases. For example, a ratio of 4:1 was associated with a 70% reduction in mortality in secondary coronary heart disease prevention and a ratio of 2.5:1 reduced rectal cell proliferation in patients with colorectal cancer. A lower omega-6:omega-3 ratio in women was associated with decreased risk for breast cancer. A ratio of 2:1–3:1 suppressed inflammation in patients with rheumatoid arthritis, and a ratio of 5:1 had a beneficial effect on patients with asthma, whereas a ratio of 10:1 had adverse consequences.
Furthermore, a high omega-6:omega-3 ratio is especially detrimental to carriers of certain genetic variations. For example, minor allele carriers of the APOA5 gene have elevated triglycerides levels and minor allele carriers of 5-lipoxygenase polymorphism in the gene promoter region exhibit increased risk for atherosclerosis. Other gene polymorphisms that are affected by this ratio include CD36 (a cell surface scavenger receptor) and TCF7L2 (a transcription factor). Lowering the omega-6:omega-3 ratio is particularly important for these variant carriers to prevent chronic diseases.
Fig.2 shows the fatty acid composition as well as the omega-6:omega-3 ratio in common food sources. It is clear that many plant seed oils contain no omega-3. Long-term ingestion of these oils without supplementing omega-3 from other sources will gradually incur hyperimmune responses and associated chronic diseases. It is also clear that most animal-based fats are actually well-balanced with regard to the omega-6:omega-3 ratio (chicken fat is an exception), but due to the high percentage of saturated fat, consumption of animal fat still needs to be restricted in an appropriate amount. Overall, canola oil has the most balanced fatty acid composition, not only due to a good omega-6:omega-3 ratio, but also because it contains a high percentage of monounsaturated fat which is beneficial to human health. Olive oil, although moderately high in the omega-6:omega-3 ratio, also contains a high percentage of monounsaturated fat. Most importantly, olive oil also contains a high amount of antioxidants and the substance squalene that has been shown to have anti-cancer effects. Therefore, olive oil is another good choice of healthy food oil. Deep sea fish oils such as salmon fat are excellent sources of omega-3. Flaxseeds oil is also a rich source of omega-3. It is a good option to use for a omega-3 supplement.
The opposing effects of omega-3 and omega-6 fatty acids on human health are due to three molecular mechanisms: 1) they compete for the same set of enzymes to produce signaling molecules that have opposing physiological functions. While omega-3 derived signaling molecules are pro-inflammatory, omega-6 derived are anti-inflammatory; 2) they compete for direct transcription factors binding to modulate the expression of different sets of target genes; and 3) they compete to incorporate into cell membranes, directly impacting the function of the membrane.
Once consumed from the diet and inside human cells, PUFAs are stored in the phospholipids of the cell and organelle membranes or in glycerides and phospholipids of lipid bodies in human cells. When needed, these fatty acids are released from phospholipids by PLA2 (phospholipase A2) and are further converted to signaling molecules. Shorter chain PUFAs, LA and ALA, can be further processed to produce longer carbon chains and more double bonds by the same set of enzymes (enlogases and desaturases). However, omega-3 and omega-6 fatty acids are not inter-convertible in human and animals. All the longer chain products derived from omega-3 fatty acids remain omega-3, and omega-6 derivatives remain omega-6 (Fig.3). For example, AA (omega-6) can be synthesized from LA (omega-6), but not from ALA (omega-3) in the human body. Similarly, DHA (omega-3) and EPA (omega-3) can be synthesized from ALA (omega-3), but not from LA (omega-6). In addition, both types are also precursors of (and share the enzymes to produce) signaling molecules that work through cell surface receptors like the GPCRs (G protein coupled receptors) as well as through nuclear hormone receptor transcription factors directly to regulate processes related to cardiovascular function and inflammation response.
Overall, the signal molecules derived from omega-6 are pro-arrhythmic (irregular heart beat or muscle contraction) and pro-inflammatory while the signal molecules derived from omega-3 are anti-arrhythmic and anti-inflammatory (Table 3).
|Types||AA (ω-6) derived||EPA & DHA (ω-3) derived|
|Thromboxanes||TXA2||Platelet activator||TXA3||Platelet inhibitor|