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“Omega Ratio” Matters to Mood; Low Cholesterol Levels Deemed Depressing
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More evidence that fat-intake imbalance worsens mood and induces inflammation; Driving cholesterol levels too low may promote mental problems

by Craig Weatherby

Two new studies on depression and dietary fats combine to highlight the importance of omega-3s, the dangers of consuming too many omega-6 fats, and the risks of driving cholesterol levels too low.

During the past four decades, researchers have been preoccupied with the ways in which health – especially cardiovascular health – is impacted by people’s intake of cholesterol and saturated fatty acids from meats and dairy foods, and by polyunsaturated fatty acids from seed oils.

Key Points

  • People with a history of self-harming have low omega-3 and cholesterol levels.

  • Having a high ratio of omega-6 fatty acids to omega-3s in your diet increases bodily inflammation and depression risk.

  • Inflammation and low omega-3 levels are independent risk factors for depression, and combine to make matters worse.

Although the idea that cholesterol levels are the key factor in heart health has begun to crumble in the face of contrary evidence, cholesterol-lowering remains the number one way doctors try to reduce cardiovascular risk.

But findings from Ireland add weight to existing concerns about excessive cholesterol-lowering.

Cholesterol levels can go too low for mental health

Commander Joe Hibbeln, M.D. of the US Public Health Service is a psychiatrist at the National Institute on Alcohol Abuse and Alcoholism, where he treats outpatients and conducts clinical trials related to nutrition and mental health.

We’ve spoken with him repeatedly about omega-3s and depression: opportunities we’ve prized, since Joe Hibbeln is one of the most published, respected, and innovative researchers in this field.

Dr. Hibbeln co-authored a study with researchers at the National University of Ireland, whose results question the wisdom of conventional attitudes toward cholesterol.

Cholesterol is essential to proper nerve and brain function, and it’s known that very low cholesterol levels can be dangerous to mental health.

As the authors said at the outset of their report, “Low cholesterol has been reliably demonstrated in people who self-harm.” (Garland MR et al 2007)

The US-Irish team wanted to determine whether people who self-harm – for example, attempt suicide or cut themselves – also have low levels of polyunsaturated omega-3 and omega-6 fatty acids.

Dr. Hibbeln and his colleagues recruited 40 patients with a history of self-harm and 40 healthy control subjects, and measured their blood levels of cholesterol and fatty acids.

They found that depressed patients with a history of self-harm averaged lower total cholesterol levels (163 mg/dL) and lower levels of omega-3 and omega-6 fatty acids, compared with the non-depressed controls (189 mg/dL cholesterol).

The patients with the lowest levels of omega-3 and omega-6 fatty acids also scored the worst on tests of impulsivity and depression.

No association was found between the self-harming patients’ total or LDL cholesterol levels and their mental health test scores, probably because they already had very low cholesterol levels.

As Dr. Hibbeln’s group wrote, “Lower plasma [omega-3 and omega-6] levels combined with low cholesterol concentrations were associated with self-harm as well as impulsivity and affect [depression].” (Garland MR et al 2007)

And given the import of the findings summarized below, it seems unlikely that a lack of omega-6s is the main problem for these patients.

Instead, it is seems more plausible that self-harming impulses stem from their low average cholesterol levels combined with their lack of omega-3s.

The overlooked “omega factor” in depression

Medical authorities have long advocated replacing saturated fats with polyunsaturated fats, as a proven way to improve heart health.

But until very recently, they focused solely on the omega-6 polyunsaturated fatty acids that increasingly dominate the fatty part of Americans’ diets.

While unfortunate, this omega-6 emphasis was not unreasonable, for two reasons:

  1. Research on omega-3s was lacking;

  2. Doctors had ample evidence that omega-6 fatty acids could lower cholesterol levels, which was and remains –to an excessive extent – a key focus of cardiovascular prevention efforts.

This single-minded focus on cholesterol, saturated fats, and omega-6 fatty acids has had negative consequences:

  • Americans consume far too many omega-6 fatty acids and far too few omega-3 fatty acids--a pattern with broadly adverse consequences;

  • Much of the omega-6 fat Americans eat comes in the form of “trans” omega-6 fats, created when vegetable oils are hydrogenated (partially saturated) to increase their shelf life or resistance to the heat of frying.

  • The links between high cholesterol levels and risk of heart-related death are weak and inconsistent.

  • Excessive avoidance of cholesterol or excessive lowering of cholesterol production in the body via drug therapies can lead to long-term health problems.

Doctors’ narrow focus on the balance between saturated fats and omega-6 fatty acids led them to overlook early evidence that the ratio of omega-6 to omega-3 polyunsaturated fatty acids in people’s diets is just as important to cardiovascular health.

Yet, people’s omega-6:omega-3 intake ratio impacts a much broader range of preventive health issues I addition to heart health, ranging from Alzheimer’s, allergies, and arthritis to diabetes, cancer, and depression.

The current scientific consensus is that the human body evolved and thrives on diets providing about three molecules of omega-6s to every molecule of omega-3s.

But the average American consumes a whopping 10 to 40 times more omega-6s than omega-3s, and this imbalance is a prescription for accelerated aging and degenerative disease (See “New Report Finds Americans Need Far More Omega-3s”).

The results of a new study add impetus to the urgency of re-balancing American diets away from excess omega-6 intake and toward increased omega-3 intake.

Omega-imbalanced diets found to drive inflammation and depression

Most dietary omega-6s come from America’s most common vegetable oils – corn, soy, canola, sunflower, safflower, and cottonseed – which predominate in home cooking and in packaged and restaurant foods.

Why is fish oil, not flax oil, the preferred omega-3 supplement?

  • Humans can survive and thrive on the short-chain omega-3s in leafy green plant foods, but only because our bodies can convert about 10 percent of them to the long-chain omega-3s (EPA and DHA) needed to make optimally healthy cell membranes and the critical, anti-inflammatory messenger chemicals called eicosanoids.
  • Fish and fish oil are the only good dietary sources of long-chain omega-3s. This is why long-chain omega-3s are also known as “marine” omega-3s, and why nutrition experts recommend taking fish oil rather than flax oil as your primary source of supplemental omega-3s.

Americans also get lots of omega-6 fat from factory-farmed cattle, pigs, and poultry, which are fed grain-heavy diets high in omega-6s and low in omega-3s.

(Nutrition-savvy doctors recommend eating “free-range” meats and poultry raised on pasture grasses, which, compared with grains like corn, are high in omega-3s and low in omega-6s.)

Researchers from Ohio State University took blood samples from 43 older adults (average age 67) and compared their omega-6 and omega-3 blood levels with the blood levels of pro-inflammatory immune-system proteins (cytokines) in participants’ blood (Kiecolt-Glaser JK et al 2007).

They found that people with high ratios of omega-6 to omega-3 (i.e., lots of omega-6, not much omega-3) were more likely to suffer from depression and inflammatory diseases.

The subjects’ symptoms of depression were assessed using a standard test called the Center for Epidemiological Studies Depression Scale.

They reported that the participants who met the diagnostic criteria for depression had significantly higher omega-6/omega-3 ratios as well as higher levels of pro-inflammatory cytokines, compared with those who were not clinically depressed.

In other words, having a high omega-6/omega-3 intake ratio makes it more likely that a person will be depressed and display low-grade “silent” inflammation: the kind associated with increased risk of heart disease, osteoporosis, senility, and diabetes.

The Ohio team also found that having high omega-6/omega-3 ratios and clinical depression raised levels of inflammation more than either factor alone.

Depression, inflammation, and omega-3s: the close connections

These are some of the recent findings in support of the idea that depression could be a condition induced by low-grade systemic inflammation (Das UN 2007):

  • Depression occurs more frequently in people whose intakes of omega–3 fatty acids are low.

  • Administering pro-inflammatory cytokines to animals and people induces symptoms of depression.

  • Many depressed patients have high blood levels of pro-inflammatory cytokines.

  • Depression is more frequent in people with immune-system dysfunctions characterized by high levels of pro-inflammatory cytokines.

  • Anti-depressant drugs block symptoms of sickness induced by pro-inflammatory cytokines.

  • Pro-inflammatory cytokines activate the hypothalamo-pituitary-adrenocortical axis (HPAA), which is also activated in depressed patients.

  • Pro-inflammatory cytokines activate the same cerebral noradrenergic systems active in depressed patients.

  • Several pro-inflammatory cytokines activate serotonin-related brain systems implicated in major depression and its treatment.

Conversely, depression could promote inflammation, since the central nervous system regulates the production of pro-inflammatory cytokines.

And there are reasons to believe that dietary omega-3s could simultaneously discourage inflammation and any depression it might promote (Das UN 2007):

  • People diagnosed with depression have low blood and cell membrane levels of omega-3s.

  • Omega-3 fatty acids suppress the production of key pro-inflammatory cytokines -10 and, finally, by acting like inhibitors of cyclooxygenase.

  • Controlled clinical trials and other studies have shown that consumption of long-chain marine omega-3s (EPA and DHA) yields a longer period of remission in depressed patients.

Fortunately, this vicious, self-reinforcing cycle can be broken by taking four steps:

  1. Avoid packaged and restaurant foods.

  2. Avoid standard vegetable oils in favor of olive oil, macadamia nut oil, and “hi-oleic” sunflower or safflower oils.

  3. Favor fish and grass-fed meats over conventionally raised beef, pork, and poultry.

  4. Avoid farmed salmon, which is fed grain and is therefore high in omega-6s. (In the only human test conducted to date, feeding men standard farmed salmon raised their blood levels of pro-inflammatory cytokines. See “Farmed Salmon's Diet Yields Unhealthful Cardiovacular Effects”.)

Omega-3 EPA affects blood flow and the immune system in ways that enhance brain function. Omega-3 DHA makes it easier for brain cell membranes to change shape and transit electrical signals.


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