How Signals Get Skewed

Biology is a balancing act, and a delicate one at that. Often, seemingly healthy diets can be lacking or overabundant in one or more essential nutrients. And when such an imbalance occurs, it can undermine health, often surreptitiously. Depression may be a case in point.

Omega-3s are a cornerstone group of polyunsaturated fatty acids, and one for which the balance is particularly critical. Composed of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both of which are found in marine sources, and alpha-linolenic acid (ALA), found in plants, omega-3s are not made by the body and must be supplied by diet, making them essential fats.

Omega-3s are highly concentrated in the brain, where they are integral to the function of nerve cell membranes. Throughout the body they are linked to production of compounds—metabolites known as resolvins, maresins, and protectins—that help counter inflammatory processes.

The problem is that a sufficient level of omega-3s is difficult to achieve—and the cause is not exclusively inadequate omega-3 intake. Blame must be shared with the omega-6 fatty acids, related polyunsaturated fatty acids found in an overwhelming number of foods, especially processed ones—vegetable oils, dairy, meat (including that from animals raised on grain rather than grass), cereal, salad dressings, Burger King onion rings, and much more. Omega-6s are also essential to a healthy body, particularly to the human cell membrane. However, they are metabolized by some of the same enzymes that process omega-3s, which leads to a certain amount of biologic competition.

Bodies function optimally when omega-6 and omega-3 fatty acids are consumed in a roughly 1:1 ratio. The human diet once ideally balanced the fatty acid groups, and it still does in hunter-gatherer societies. Unfortunately, contemporary diets supply a wildly imbalanced ratio, often a 20:1 preponderance of omega-6s. Not only do they usurp metabolic pathways, they also readily undergo oxidation, leading to the expression of inflammation-inducing cytokines.

A balanced ratio of omega-3s and -6s keeps inflammation in check, reining in the cytokines. By fostering inflammation, today's omega imbalance is thought to play a contributing role in conditions ranging from diabetes to stroke to major depression.

"The food industry has overloaded our diet with omega-6, which when consumed in excess creates chronic inflammation," says Ohio State University's Akhlaq Farooqui, a longtime researcher of fatty acid metabolism and neural processes. His studies suggest that consumption patterns of omega fats lead to a chronic, mild level of inflammation that flies under the radar of the body's immune system without triggering an acute defensive response but, over time, induces subtle changes in neurotransmitters. Such changes, in turn, beget depressive symptoms.

Clinical studies have shown that omega-3s benefit patients with major depression. "Now the question is which omega-3s are responsible for that effect," says Beth Levant, a professor at the University of Kansas Medical Center. Her work focuses on the link between omega-3s and neuropsychiatric function, notably postpartum depression.

DHA is the predominant species of omega-3 in the brain, but it may not be the fatty acid most relevant to all brain functions. Says Levant: "Based on emerging clinical trials, in which different omega-3 formulations are given to patients with major depression, the evidence points to EPA as the omega-3 with the largest antidepressant effect."

Don't write off DHA, however. Ongoing studies suggest that it is concentrated in brain blood vessel walls and is key for maintaining the blood-brain barrier, shielding the brain from toxins and pathogens.

How Inflammation Leads to Depression

Omega-6 fats are readily oxidized, leading to production of proinflammatory cytokines, which in turn act on key neurotransmitter systems. Availability of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) at synapses is diminished, changes that dampen motivation and increase alarm and anxiety. At the same time, the excitatory neurotransmitter glutamate (Glu) is overexpressed, diminishing the capacity for new behavior by lowering levels of brain-derived neurotrophic factor (BDNF).

Fatty Facts

• Omega-3s and omega-6s are both poly-unsaturated fatty acids, meaning there are many double bonds in the molecules' structures.
• The 2015-2020 Dietary Guidelines for Americans recommends consumption of at least 8 ounces of seafood per week, including species rich in DHA.
• The American Heart Association recommends intake of 1 gram a day of EPA and DHA for people with heart disease and two meals of oily fish a week for those without heart disease.
• Studies show that intake of 1 gram of DHA daily boosts cognitive function in adults, improving memory and processing speed.
• A DHA-rich diet can support the development of cognition in children.
• Fatty fish like trout, salmon, and tuna contain the most omega-3s. Generally, the amount of omega-3s is related to the fat content of the species.
• Tilapia and catfish contain omega-3s but also high levels of unhealthy fatty acids. They have not been shown to have positive effects on heart health.
• For nonfish eaters, algal oil is a source of omega-3s.
• Plant-based ALA is converted into EPA and DHA in the body, but controversy surrounds how much conversion takes place.
• The disproportionately large amounts of omega-6s that Americans consume come primarily from corn oil, sesame oil, soybean oil, and sunflower oil.
• Symptoms of omega-3 deficiency include fatigue, dry skin, moodiness, depression, memory problems, and cardiovascular problems.