How does our diet today differ from that of our ancestors? What is the role of fats in our biology that influences our health? What are the recommendations for essential dietary fats? The second part of this series on fatty acids (FAs) will address these questions.
Changes in ratio of n-6 to n-3 FA over time
Researchers have suggested that our ancestral diets were very different from our diet today. Nutrition estimates of our Paleolithic ancestors (400,000-45000 years ago) are variable total fat intake (21-58% of energy), higher in polyunsaturated fats (PUFAs) and lower in saturated fat. Hunter-gatherers, whose diets consisted mostly of wild game, birds and fish, are estimated to have eaten equal quantities of the essential fatty acids (EFAs) n-6 and n-3 FAs (estimated ratio of 1:1).
During the Agricultural Revolution (10,000 years ago), cereals became a part of our food supply and humans became dependent on cereal grains for the major proportion of their food supply. Cereal grains, which are high in carbohydrates and n-6 FAs, and low in n-3 FAs and antioxidants, replaced a large proportion of fresh vegetables and fruit.
The Industrial Revolution (~140 years ago) saw a shift in the ratio of dietary n-6 to n-3 corresponding to the increase in domestic animal production for meat consumption. The eicosapentaenoic acid (EPA; n-3) content of wild animals averages about 4% of FAs in their fat, while domestic animals raised for meat production sometimes have undetectable amounts of EPA in their tissues. Overall, n-6 FA consumption increased at the expense of n-3 FAs.
This change also reflected the modern plant food industry as use of cereal grains for domestic livestock grew. New technologies enabled mass processing of vegetables for oil used in cooking and as food additives. Hydrogenation of oils to solidify them facilitated the increase of trans-fatty acids (TFAs) in the diet.
Modern agriculture decreased the n-3 FA content in many foods. Food from wild plants contains a favorable balance of n-3 and n-6 FAs. Wild-caught fish contains more n-3 FAs than fish grown in fish farms. Similarly, eggs from free-range chickens have a n-6:n-3 ratio of 1.4:1 whereas the typical USDA eggs have a ratio of 19:1.
Between 1935-1939, the ratio of dietary n-6:n-3 FAs was about 8:1, and in 1985, that ratio increased to 12:1. Accompanying this was a shift in the consumption of fats, oils, fruit, vegetables, and nuts, accounting for 68% of the alpha-linolenic acid (ALA; n-3) content in the food supply.
PUFAs in the American diet today: an imbalance of n-3:n-6
In today’s American diets, PUFAs contribute ~7% of total energy intake and 19-22% of energy intake from fat. These levels are within recommended intakes for both men and women. Linoleic acid (LA; n-6) contributes 84-89% of total energy from PUFA. Only 9-11% of total PUFA energy (1.1-1.6 g/d) is derived from ALA. The highly unsaturated fatty acids (HUFAs) -EPA and DHA together- provide less or equal to 0.1-0.2% (0.2 g/d) of energy intake.
Grains, vegetables, meat, fish and poultry are the predominant contributors of ALA to the diet along with fats, oils and salad dressings. To increase ALA intake, increase consumption of vegetable oils high in ALA at the expense of other fats in the diet. Because the conversion of ALA to the HUFAs is inefficient, augmenting EPA and DHA intake may be a better approach. To appreciably boost EPA and DHA intake, it will be necessary to increase fish oil consumption.
Biological roles
When EFAs are excluded from the diet of animals, they display retarded growth, dry skin, kidney lesions, and early death. We now know that these fatty acids play an important role in cardiovascular health, hypertension, diabetes, cancer, arthritis and other inflammatory diseases in humans.
The short- and long-term effects of the balance between n-6 and n-3 FAs are mediated by eicosanoid metabolism, gene expression, and cytokine production. The n-3 and n-6 FAs have opposing physiological functions and they often compete in enzyme activity. For example, LA and ALA compete for the rate-limiting enzyme Δ6-desaturase in the synthesis of long-chain PUFAs.
Membranes
The primary long-term and non-specific effects of PUFAs are their influence on cell membranes. Over time, dietary fats are incorporated into these membranes forming two layers of fatty acids. The number of double bonds in the chain influences FA structure in the cell membrane and thus alters membrane-associated functions, even in the brain.
The building blocks of all cell membranes are lipids, making up about 50% of the mass of most membranes. Two fatty acid chains attach to a phosphate head forming a phospholipid. These molecules form a stable bilayer with the fatty acid tails buried in the interior of the membrane.
The physical properties of cell membranes are largely determined by their flexibility. An important role of lipid bilayers is that they perform as two-dimensional fluids in which individual molecules are free to rotate and move sideways. This fluidity is influenced by temperature and lipid composition.
Phospholipids containing unsaturated and short-chain fatty acids are less rigid and more fluid. Some fats such as cholesterol that are incorporated into the membrane make it stiff and resistant to interaction with other substances inside and outside the cell.
The remaining 25-75% of cell membranes is made up of various proteins, which are inserted into the bilayer and carry out specific functions. Consequently, the lipid composition of the membrane affects activity of transport proteins and cellular receptors in the membranes. Thus changes in membrane fluidity dynamics can impact the functioning of the cell.
Signal molecules
Membrane FAs also serve as parent molecules for FAs inside the cell. Enzymes release and convert membrane phospholipids to FAs which are active and can serve as signaling molecules within cells. Of these signaling substances, arachidonic acid has received the most attention because of its bioactive products called eicosanoids (see diagram depicting the pathway).
Dietary EPA and DHA partially replace the n-6 FAs, especially arachidonic acid, in most cell membranes of platelets, erythrocytes, liver and immune cells (neutrophils, monocytes). However, n-6 fatty acids are the most abundant in cell membranes and serve as the precursor for arachidonic acid and affect eicosanoid synthesis.
What are eicosanoids?
In response to certain signals, arachidonic acid is released from the cell membrane and further converted to eicosanoids. Because n-6 FAs are typically the primary lipids in cell membranes, most eicosanoids are derived from these precursors.
Eicosanoids have 20-carbons and have widespread biological activity. They have a short half-life of tens of seconds to minutes before they are degraded. Therefore, eicosanoids typically act locally by passing on signals between nearby cells (paracrine) and acting on the cells from which they are synthesized (autocrine). They bind to receptors in the cell membrane surface by which a cascade of signals inside the cell elicits a response.
There are several types of eicosanoids differing in their structure and biological activity. Examples are prostaglandins, thromboxanes, leukotriens, and lipoxins. Commonly referred to as ‘good’ eicosanoids and ‘bad’ eicosanoids, those of the n-3 type generally oppose the functions of the n-6 type. Nevertheless, eicosanoids derived from n-3 FAs are less active than those from n-6 FAs.
These substances mediate a variety of functions. The most studied effects have been on cells of the immune system, on blood clotting regulation, and smooth muscle. Eicosanoid products formed in large amounts contribute to formation of thrombus (blood clots in vessels), atheromas (fatty deposits in an artery), allergic and inflammatory disorders (especially in susceptible individuals), and proliferation of cells. Consequently, n-6 FAs and eicosanoids are implicated in the development of many diseases.
Gene Expression
Recent developments in molecular biology techniques have demonstrated that HUFAs can regulate expression of genes independently from their role in cell membranes. Current research concentrates on mediators of gene regulation that are stimulated by metabolites of the EFAs: peroxisome proliferator-activated receptors (PPARs). These nuclear receptors are found in many tissues cells and are involved in lipid metabolism as well as several other metabolic systems. Additionally, HUFAs can also regulate several other genes, especially in the liver, that are involved with metabolism.
Immune System
The amount and type of lipids modulate the immune system because incorporation of FAs into tissues modifies immune reactions. As previously mentioned, the balance of dietary PUFAs can alter arachidonic acid metabolism and eicosanoids synthesis thus influencing inflammatory activity.
The n-3 FAs are especially potent therapeutic agents for inflammatory conditions. When the n-3 PUFA intake is high, the balance of n-6 and n-3-derived eicosanoids is shifted towards a mixture with decreased inflammatory activity. This is accomplished by n-3’s partially replacing arachidonic acid in cell membranes. For instance, EPA competes with arachidonic acid as a substrate for eicosanoids, leading to the formation of the less active leukotriene B.
A lower n-6:n-3 ratio results in a reduced production of major cytokine mediators of inflammation, such as IL-6, IL-1, and TNF-α. Various studies demonstrate that supplementing the diet with n-3 FAs (3.2 g EPA and 2.2 g DHA) without changing arachidonic acid and DHA content in normal human subjects increased EPA content more than 7-fold in immune cells (neutrophils and monocytes). Furthermore, the anti-inflammatory effects of fish oils are partly mediated by inhibiting the 5-lipoxygenase pathway in neutrophils and monocytes and impede the leukotriene B4-mediated function of LTB5.
Cardiovascular Disease (CVD)
Epidemiological and clinical studies suggest that consuming n-3 FAs reduces the risk of CVD. A diet high in n-6 FAs increases blood viscosity, vasospasm, vasoconstriction, and decreased bleeding time. Plus, a higher ratio of n-6:n-3 FAs in platelet membranes is associated with a higher death rate from CVD.
Because studies strongly suggest that inflammation facilitates the initiation of CVD, dietary interventions may play a role in reducing disease incidence. Many experiments in animals and tissue cultures, as well as clinical and population trials, support evidence that n-3 FAs from fish and marine oils favorably impact heart disease.
Intervention studies suggest that intakes of 200 g/day of fish or 2 g of n-3 EPA and DHA improve several hematological parameters implicated in the etiology of CVD. Research suggests that n-3 FAs:
- Decrease risk for arrhythmias, irregular heartbeats hat lead to sudden cardiac death.
- Decrease risk for thrombosis, which can lead to hear attack and stroke.
- Decrease triglycerides.
- Slightly lower blood pressure
- Reduce inflammatory response.
- Increase endothelial function.
- Slow the progression of atherosclerosis.
Body Composition
Although all fats provide the same amount of energy per gram (9 kcal), the effects of fats on weight gain differ according to their chemical makeup. Consumption of a diet high in saturated fat seems to be associated with increased risk of gaining weight, while PUFAs may reduce that risk. In fact, some studies suggest that PUFAs protect against developing obesity. While the evidence for this is strong in animals, preliminary studies suggest that the same may occur in humans. Pharmacological doses of fish oil (40% of energy intake) have been shown to decrease fat mass in rats, but this dosage may not be practical or healthy in humans. Many studies also suggest that monounsaturated fats (MUFAs) and n-3 FAs may be more effective than n-6 FAs.
The question remains if altering the fat composition of an energy-restricted diet significantly contributes to weight loss. Some studies suggest that the HUFAs bestow a partitioning effect by decreasing fat mass and sparing lean body mass. This is supported by evidence in animal models, although the data in humans remains inconclusive.
Recommended intake
Nearly all medical organizations recommend a reduction in saturated fats (to ~10% of daily energy intake) and elimination of TFAs. While they also urge increasing dietary PUFAs, the recommendations for specific FAs have been inconsistent. Recently an international working group of scientists met to discuss the scientific evidence and formed recommendations for dietary intake of EFAs. The consensus reached supports a reduction of dietary n-6 FAs while increasing n-3 FAs to reduce excesses of arachidonic acid and eicosanoids.
Because too much LA and arachidonic acid and not enough n-3 FAs in the diet can cause these excesses, dietary changes can be employed to avoid their adverse effects. Reducing the amount of plant oils rich in LA, which converts to arachidonic acid, and simultaneously increasing the amount of dietary n-3 FAs can achieve this. Depending on the overall composition of an individual’s diet, supplementing with flax oil often corrects imbalances of FAs.
The enzyme that converts LA to arachidonic acid is the same that converts ALA to the highly HUFAs (EPA and DHA). Each of these precursors competes for this same enzyme. Thus dietary ALA can inhibit the conversion of the typically large amounts of LA in the Western diet.
Additionally, because the conversion of ALA to n-3 HUFAs is the rate-limiting (and rather inefficient) step, intake of HUFAs will help achieve a healthier diet. Fish oils contain the highest levels of EPA and DHA and studies have documented a rise in levels of these FAs in the body after consumption of at least two servings per week of fatty fish such as salmon and mackerel.
However, several concerns surround eating commercial fish. Ocean-caught fish may contain environmental contaminants, especially heavy metals. Although levels of these contaminants have been verified in older predatory fish, many species of fish that contain n-3 FAs are low in contaminants such as mercury. As mentioned previously, farmed fish tend to contain a higher profile of n-6:n-3 FAs because of their diet. Individuals will have to weigh these concerns with the amount of fish they eat.
An alternative to eating fish is fish oil supplements. Although more expensive, distillation methods can remove contaminants as well as any fishy taste. Additionally, several producers chemically analyze their products for heavy metals. Another source of EPA and DHA is plant or non-fish marine extracts. However, they are not readily available on the market and relatively expensive.
Increasing evidence suggests that MUFAs should contribute a major portion of dietary fat intake. The American Association for Diabetes recommends that 60-70% of the daily total energy intake should be partitioned between carbohydrates and MUFAs. These FAs, like HUFAs, improve the plasma lipid profile and are linked with decreases in atherosclerosis markers. Additionally, MUFA-enriched diets have been associated with higher vitamin E status, thus offering a protective effect on oxidative status. Because lipid peroxidation is associated with high intakes of PUFAs, a balance of dietary MUFAs and PUFAs may optimally reduce risk of cardiovascular disease, especially long-term.
We are what we eat
Research continues to explore and define the roles of nutritional components in our health and well-being. The historic perspective of low-fat diets is now challenged. We now know that the type of fats consumed is possibly more important than how much.
This two-part article provided a basic overview of the role of essential fatty acids. By now, readers have learned:
- Modern Western diets are vastly different from that of our ancestors and are likely a contribution to the increase in disease incidence.
- The size and structure of fatty acids determines their roles in the body.
- They are a large and important component of cell membranes in all tissues.
- Fatty acids also serve as signals inside the cell independently of cell membranes.
- Absolute and relative levels of essential fatty acids determine their biological effects.
- Products of n-6 fatty acids form substances that mediate our immune system. Excess levels are also associated with development of diseases such as heart and circulatory systems.
- World health and medical organizations recommend increasing levels of n-3 and lowering n-6 fatty acids. In addition to these changes, they advise including monounsaturated fatty acids in our diet.
