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Nutrition and Metabolism

Omega-3 and Omega-6 Fatty Acids

Fat is perhaps the most diverse class of dietary macronutrients (the other three classes are carbohydrates, proteins and fibers) concerning the nutrition value and physiological effects on human health. Currently, most people understand the good (unsaturated fat), the bad (saturated fat) and the ugly (trans fat) that have been described in “Fat Metabolism 101”.  We know that animal fat derived oils are not good to human health due to their high content of saturated fatty acids and cholesterol, and that plant seeds derived oils are good due to the high content of unsaturated fat and zero cholesterol.  Few people, however, realize that not all unsaturated fats are good to human health.  Many plant seeds oils such as sunflower oil, peanut oil and corn coil are rich in polyunsaturated fatty acids (PUFAs) that are pro-inflammatory and devoid of the PUFAs that are anti-inflammatory.  On the other hands, some plant seeds oils such as rapeseed oil (Canola) and olive oil has balanced PUFAs that are overall good for human health.  Therefore, it is important to distinguish the type of PUFAs in dietary oils.

PUFAs are fatty acids that have two or more double bonds in each molecule.  There are two types of PUFAs in dietary oil: ω-3 and ω-6.  They are distinguished by the position of the first double bond counting from the methyl end of the carbon chain.  The ω-3 fatty acids are PUFAs with the first double bond occurs at the third carbon atom from the methyl end of the carbon chain. The ω-6 fatty acids are PUFAs with the first double bond occurs at the sixth carbon atom from the methyl end of the carbon chain (Fig.1).

Figure 1. The structural representation of ALA (ω-3) and LA (ω-6), two essential fatty acids and the most common PUFAs found in dietary oil. The red numbers represents the carbon atoms counting from the methyl end of the chain.  The blue counts from the carboxyl end.

The most common ω−3 fatty acids in human diet include ALA, EPA, and DHA.  The most common ω−6 fatty acids are LA and AA (Table 1).  The ω−3 fatty acid ALA and the ω−6 fatty acid LA are also essential fatty acids since they are indispensible for normal physiology yet human body cannot synthesize them, thus has to obtain them from diet. Essential fatty acid deficiency leads to dermatitis, decreased growth in infants and children, increased susceptibility to infection, and poor wound healing. In human cells, besides dietary intake, all the long-chain ω−3 fatty acids are synthesized from ALA and all the long-chain ω−6 fatty acids are synthesized from LA. 

Table 1. The most common ω−3 and ω−6 fatty acids and their dietary sources.

Types Abbreviation Common Name Structure Dietary Sources

ω-3

ALA (essential) α-Linolenic acid C18 : 3 Flaxseeds oil, olive oil, rapeseeds oil (Canola)
EPA Eicosapentaenoic acid C20 : 5 Fish oil, marine algae
DHA Docosahexaenoic acid C22 : 6 Fish oil, marine algae
ω-6 LA (essential) Linoleic acid C18 : 2 Corn, soybean, and peanut oils. Sunflower seeds oil
AA Arachidonic acid C20 : 4 Peanut oil, meat, dairy products and eggs

Overall, ω−3 fatty acids are anti-cardiovascular diseases and anti-inflammation while ω−6 fatty acids are pro-cardiovascular diseases and pro-inflammation. Long-chain ω−3 fatty acids (EPA and DHA) provide many health benefits with regard to its cardiovascular diseases prevention and anti-inflammation effects. DHA, a long-chain ω−3 fatty acid, is also directly involved in visual and neuronal cells development. Adequate amount of ω−6 fatty acids are also beneficial to human health since many bioactive signaling molecules, especially the ones that are involved in immune response and cardiomyocytes contraction, are derived from them. However, in modern Western diet, ω−6 fatty acids tend to be over supplied while ω−3 fatty acids under supplied due to industrialized food oil production from sources that were otherwise unavailable. The overwhelmingly over-intake of ω−6 leads to hyper immune responses and interferes with the proper function of ω−3 fatty acids, causing detrimental effects that are blamed for chronic cardiovascular diseases and inflammatory responses (Table 2).

Table 2.  The effects of ω−3 and ω−6 fatty acids on chronic diseases.

Chronic Diseases Risk Factors Comments ω-3 ω-6
Cardiovascular Diseases Arrhythmias (irregular heart beat) Causes sudden cardiac death Lowers Increases
Thrombosis (clot) Leads to myocardial infarction or stroke Lowers Increases
Aatherosclerotic plaque Leads to atherosclerosis Lowers Increases
HDL Good cholesterol Increases Lowers
LDL Bad cholesterol Lowers Increases
Triglycerides Cardiovascular risk factor Lowers Increases
Inflammatory Responses 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 ω−3 and ω−6 fatty acids, it is advocated that a healthy dietary regime should contain a balanced ω−6:ω−3 ratio.  Human beings evolved on a diet with a ratio of ω−6:ω−3 about 1:1 and our genetic makeup is well adapted to this ratio. Modern Western diets are deficient in ω-3 while are excessive in ω-6 fatty acids, exhibiting a ω−6:ω−3 ratio from 15:1 to 17:1.  Epidemiology and dietary intervention studies have concluded that while the exceptionally high ω−6:ω−3 ratio promotes the development of many chronic diseases, reduced ω−6:ω−3 ratio prevents or reverses these diseases.  For example, a ω−6:ω−3 ratio of 4:1 was associated with a 70% reduction of mortality in secondary prevention of coronary heart disease. A ratio of 2.5:1 reduced rectal cell proliferation in patients with colorectal cancer. The lower ω−6:ω−3 ratio in women with breast cancer was associated with decreased risk. 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 ω−6:ω−3 ratio is especially detrimental to populations with certain genetic variations.  For example, the minor allele carriers of the APOA5 -1131T>C polymorphism have elevated triglycerides levels and the minor allele carriers of 5-lipoxygenase polymorphism in the gene promoter region exhibit increased risk for atherosclerosis. Other gene polymorphisms that interacts with the ω−6:ω−3 ratio include CD36 (a cell surface scavenger receptor) and TCF7L2 (a transcription factor) genotypes. Therefore, keep a low dietary ω−6:ω−3 ratio is important to prevent chronic diseases. 

Fig.2 provides the fatty acids composition as well as ω−6:ω−3 ratio in common food sources. It is noticeable that many plant seeds oils contain no ω−3.  Long term usage of these oils without supplement from other ω−3 rich sources will gradually and accumulatively inflict hyper immune response and associated chronic diseases.  It is also noticeable that most animal based fat are actually well balanced with regard to the ω−6:ω−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 represents the most balanced fatty acids composition, not only a good ω−6:ω−3 ratio, but also a high percentage of monounsaturated fat that is beneficial to human health.  Olive oil, although moderately high in the ω−6:ω−3 ratio, also contains high percentage of monounsaturated fat.  Most importantly, olive oil also contain high amount of antioxidant and the substance squalene that has been shown 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 ω−3.  Flaxseeds oil is rich in ω−3. It is a good source of ω−3 supplement.

Figure 2. The fatty acid composition and ω-6:ω-3 ratio in most common dietary fat.

The opposing effects of ω−3 and ω−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 ω−3 derived signaling molecules are pro-inflammatory, ω−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 impact the function of membrane.

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