The fats we eat fall into three basic types based on the length of their carbon chains and the presence (and number) of any double bonds between carbons. In the standard nomenclature, fats of varying lengths containing no double bonds are termed saturated fats, those with a single double bond are termed monounsaturated, and those with two or more double bonds, polyunsaturated or PUFA.
The PUFA family nomenclature further divides according to the location of the first double bond; they may be either an omega-6 (when the bond appears 6 from the end) or omega-3 (3 from the end). The many biologic functions of PUFAs, from control of blood pressure to blood clotting to brain development, are determined by the location of the double bond. In broad terms, omega-3s (also called n-3s) are anti-inflammatory in nature, and omega-6s (also called n-6s) are pro-inflammatory.
By modifying other fatty acids, the body can make all the fatty acids it needs, with two exceptions: linoleic acid (LA) and alpha-linolenic acid (ALA), which are deemed “essential.” The n-3 family of fatty acids derives from ALA, and the n-6 group from LA. Humans obtain LA dietarily, from animal fats, whole grains, and mostly nowadays from plant or seed oils such as sunflower, safflower, and corn oils. ALA can be obtained from green leafy vegetables, flaxseed, and rapeseed oil. Patterson et al. also note common ancestral sources of LA, such as nuts and olives or olive oil and oily fish, which are sources of preformed n-3 end products. The ancestral ratios of n-6:n-3 are believed to have ranged from about 1:1 to perhaps as much as 4:1.
Consumption patterns have changed in the last several decades, chiefly in the types of fats consumed, with a marked increase in the dietary intake of LA, primarily from seed oils, corn oil, and soybean oil. These changes have driven the ratio to somewhere between 10:1 and 20:1. The rise in this ratio parallels increases in the incidence of diseases involving inflammatory processes, such as cardiovascular disease, obesity, inflammatory bowel disease, rheumatoid arthritis, cancer, and neurodegenerative and psychiatric illnesses including Alzheimer’s disease and depression. High intake of n-6 PUFA coupled with low intake of n-3 PUFA shifts the physiologic state toward inflammation, clotting, vasoconstriction, and increased blood viscosity, leading to the development of diseases associated with these conditions.
PUFAs also become incorporated into cell membranes throughout the body, where they play a key role in membrane fluidity and the regulation of cell signaling processes. Other functions of PUFA require conversion (through elongation and desaturation) to a cascade of molecules, culminating, in the case of LA in arachidonic acid (AA) and ALA, into the long-chain fatty acid derivatives eicosapentanoic acid (EPA) and docosahexanoic acid (DHA). EPA and DHA are critical to kidney, liver, and brain function as well as brain development. Dysregulation of the balance between derivatives in the n-6 family over those of the n-3 family has been shown to lead to hepatic steatosis (aka fatty liver) in mice. Decreased activity of the enzymes involved in the conversion of LA and ALA to their downstream derivatives has been demonstrated in humans with fatty liver disease as well.
The Western diet is currently very high in LA, which induces an increase in the preference of these enzymes to convert the n-6 family over the n-3 family. Unfortunately, whereas conversion of the n-3 family would have an anti-inflammatory effect, n-6 conversion leads to higher levels of AA and thus to inflammatory cytokines, series 2 prostaglandins, thromboxanes, leukotrienes, and interleukins.
Long-chain PUFAs and their derivatives have been shown to regulate gene expression. By this mechanism, operating through such transcription factors as peroxisome proliferator-activated receptor alpha and nuclear factor κB, they impact the development of the so-called “diseases of affluence” related to metabolic syndrome. An abundance of n-6 fatty acids and deficiency of n-3 may contribute to the development of non-alcoholic fatty liver disease (NAFLD) by disrupting gene transcription in a way that favors the deposition of fatty acids in the liver over oxidizing them and increases de novo lipogenesis. Tipping the balance back toward normal by decreasing n-6 fat (LA) intake and/or increasing n-3 fat intake with fish oil has been shown to improve the condition.
In the cardiovascular system, under normal circumstances and with a proper balance of n-6 and n-3 PUFAs coming in, the healthy endothelium elaborates sufficient nitrous oxide and prostaglandins to maintain a balance between pro- and anti-inflammatory molecules. Numerous lines of evidence link excessive LA to atherosclerosis. In the atherosclerotic state, the balance shifts toward pro-inflammatory cytokines that induce oxidative stress and produce reactive oxygen species (ROS), resulting in vasoconstriction, vasospasm, platelet aggregation, and easier oxidation of LDL. An abundance of n-6 PUFA relative to n-3 PUFA leads to the development of a pro-inflammatory state. Similar mechanisms suggest LA may promote other inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and Alzheimer’s disease.
In sum, an unbalanced intake of dietary n-6 and n-3 PUFAs is detrimental to human health across many of the body’s systems. Patterson et al. suggest supplementing n-3 with flaxseed or fish oil, or increasing intake of fish may be a remedy. The authors oddly seem to ignore the other side of the equation, which is that reducing intake of n-6 fatty acids by avoiding the LA ubiquitous in processed foods and plant oils may be a powerful aid in improving the n-6/n-3 balance.
Drs. Michael and Mary Dan Eades are the authors of 14 books in the fields of health, nutrition, and exercise, including the bestseller Protein Power.
Dr. Mary Dan Eades was born in Hot Springs, Arkansas, and received her undergraduate degree in biology and chemistry from the University of Arkansas, graduating magna cum laude. After completing her medical degree at the University of Arkansas, she and her husband have been in private practice devoting their clinical time exclusively to bariatric and nutritional medicine, gaining first-hand experience treating over 6,000 people suffering from high blood pressure, diabetes, elevated cholesterol and triglycerides, and obesity with their nutritional regimen.
Together, the Eades give numerous lectures to the general public and various lay organizations on their methods of treatment. They have both been guest nutritional experts on over 150 radio and television shows, including national segments for FOX and CBS.