New Findings About Omega-3 Fatty Acids and Depression

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New Findings About Omega-3 Fatty Acids and Depression

 

 

 

By Alan C. Logan, ND, FRSH

 

 

 

Omega-3 fatty acids are polyunsaturated fatty acids that are considered

essential because they cannot be synthesized by the human body. Dietary sources

of omega-3 fatty acids include plants (particularly flax, canola, walnuts and

hemp) and fish (particularly ocean fish such as sardines, anchovies, salmon and

mackerel). Plants contain the parent omega-3, alpha-linolenic acid (ALA), which

can be converted into eicosapentanoic acid (EPA) and docosahexanoic acid (DHA).1

 

 

 

Dietary fish and fish oil supplements are a direct source of EPA and DHA. The

influence of ALA, EPA and DHA in human health has been the subject of intense

research over the last three decades. Although best known for cardiovascular

benefits, new findings indicate that the influence of omega-3 fatty acids in

mental health, particularly EPA, may currently be underestimated.

Epidemiological, experimental and new clinical studies have all shown a strong

connection between omega-3 fatty acids, or a lack thereof, and major depression.

 

 

 

These exciting new findings are not entirely surprising when one considers that

the brain itself is 60 percent fat and that one-third of all fatty acids are of

the polyunsaturated variety.2,3 As discussed below, the current research

highlights the critical role of these fatty acids in the central nervous system

(CNS).

 

 

 

Omega-3 Intake Declines, Depression Rates Climb

 

 

There has been a significant drop-off in omega-3 fatty acid intake within

Western countries over the last century. The opposite can be said of omega-6

intake. Although essential, omega-6-rich oils are found in abundance in the

North American food supply. Currently these omega-6 oils (corn, safflower,

sunflower, cottonseed, sesame) are outnumbering omega-3 fatty acids by a ratio

of up to 20:1.4,5

 

 

 

This ratio is a long way off the close to 1:1 omega-6 to omega-3 ratio as

recommended by the international panel of essential fatty acid experts in the

Journal of the American College of Nutrition.6 The average daily intake of

EPA/DHA combined is 130mg in North America, 520mg short of published

recommendations and 870mg short of the 1000mg recommended by the American Heart

Association in cases of heart disease.1

 

 

 

In direct contrast to the depletion of omega-3 fatty acids from the Western food

supply, the rates of depression have dramatically increased in Western

countries. In addition, depression is now occurring more commonly in younger

persons. The average age of onset of depression has continued to dip over the

last 100 years. Scientists investigating the change in rates of depression have

made it clear that these findings cannot be explained away by changes in

attitudes of health professionals or society, diagnostic criteria, reporting

bias, institutional or other artifacts.7,8 Perhaps the inadequate omega-3

intake, the major deviations in fatty acids ratios and the quarter-century-old

message that all fat is unhealthy has had an untold influence on rates of

depression.

 

 

 

Fish Consumption and Depression

 

 

There have been a number of studies that have examined national and

international fish consumption data and compared them to rates of depression.

Dr. Joseph Hibbeln of the National Institutes of Health is a pioneer in this

area. He, and his group, have shown that higher national consumption of fish for

a nation equals lower rates of depression versus countries consuming the least

amount of fish.9 He has also shown that higher fish consumption is correlated

with lower risk of postpartum depression10 and seasonal affective disorder.11

 

 

 

Other researchers have shown that even within a nation, fish consumption is

associated with lower risk of depression and higher mental health status.12,13

Finally, researches are now observing increasing rates of depression in regions

of the world that are moving away from traditional omega-3-rich diets to typical

Western foods.14

 

 

 

Laboratory Tests in Depression

 

 

The epidemiological studies clearly suggest that adequate omega-3 fatty acids

may be an important protective factor in depression. Correlation, however, does

not prove causation. To add to the strength of the epidemiological studies,

scientists have examined the levels of omega-3 fatty acids in the blood cells

and fat storage cells of those with major depression.

 

 

 

Four studies have shown that those with depression do indeed have lower levels

of omega-3 fatty acids in the blood.15-18 One of the studies showed that the

lower the level of EPA, the more severe the clinical depression.15 In addition,

a recent study showed that the patients with depression have 35 percent less DHA

in fat storage cells versus healthy controls.19

 

 

 

Experimental Studies

 

 

Over the last decade, neuroscientists have been examining the consequences of

omega-3 deficiencies in the central nervous system. Alterations in serotonin and

dopamine levels, as well as the functioning of these two important

neurotransmitters is evident in an omega-3 deficiency. The changes observed in

omega-3 deficiency in animals is strikingly similar to that found in autopsy

studies of human depression.20

 

 

 

In addition to changing serotonin and dopamine levels and functioning, omega-3

deficiencies are known to compromise the blood-brain barrier, which normally

protects the brain from unwanted matter gaining access.21 Omega-3 deficiency can

also decrease normal blood flow to the brain,22,23 an interesting finding given

the studies which show that patients with depression have compromised blood flow

to a number of brain regions.24,25 Finally, omega-3 deficiency also causes a 35

percent reduction in brain phosphatidylserine (PS) levels.26 This is also of

relevance when considering that PS has documented antidepressant activity in

humans.27,28

 

 

 

Mechanisms of EPA/DHA Regulation of Mood

 

 

DHA is found in high levels in the cells of the central nervous system

(neurons); here it acts as a form of scaffolding for structural support.29 When

omega-3 intake is inadequate, the nerve cell becomes stiff as cholesterol and

omega-6 fatty acids are substituted for omega-3.30 When a nerve cell becomes

rigid, proper neurotransmission from cell to cell and within cells will be

compromised.31

 

 

 

While DHA provides structure and helps to ensure normal neurotransmission, EPA

may be more important in the signaling within nerve cells.32 Normalizing

communications within nerve cells has been suggested to be an important factor

in alleviating depressive symptoms.33 In addition, EPA can lower the levels of

two important immune chemicals, tumour necrosis factor alpha (TNFa) and

interleukin 1 beta (IL-1ß), as well as prostaglandin E2.34

 

 

 

All three of these chemicals are elevated in depression.35-38 In fact, higher

levels of TNFa and IL-1ß are associated with severity of depression.39 Finally,

EPA has been hypothesized to increase brain-derived neurotropic factor (BDNF),

which is known to be lower in depressed patients.20 BDNF is neuroprotective,

enhances neurotransmission, has antidepressant activity and supports normal

brain structure. BDNF may prevent the death of nerve cells in depression.

 

 

 

Clinical Studies

 

 

There have been some published case reports indicating that flaxseed oil may be

helpful in cases of bipolar depression and the anxiety disorder agoraphobia.40

The first controlled clinical trial indicating that omega-3 fatty acids may be

of benefit in depression was published in 1999. In this case, 9:6 g of EPA/DHA

versus placebo led to longer periods of remission and improvement in depressive

symptoms in those with bipolar depression.41

 

 

 

Some researchers theorize that such high doses of EPA/DHA may not be necessary

and that low levels of pure EPA may be of benefit.32 In a study published in the

American Journal of Psychiatry, researchers showed that just 2g of pure EPA

could improve the symptoms of treatment-resistant depression. The researchers

found that the EPA (versus placebo), when added to an ineffective antidepressant

for one month, significantly improved depressive symptoms.42

 

 

 

A larger study published in Archives of General Psychiatry replicated these

findings, however, this time various doses of EPA were examined. Those on

ineffective antidepressants were given 1g, 2g or 4g of pure EPA or a placebo in

addition to the medication. Interestingly, the 1g daily dose of EPA led to the

most significant improvements over the three-month study; it appeared that less

was more. There were significant improvements in depressive symptoms, sleep,

anxiety, lassitude, libido and thoughts of suicide.43

 

 

 

Researchers from Taiwan Medical University published a recent study in which

they found that a 4.4g EPA and 2.2g DHA mix could alleviate depression versus

placebo in those with treatment-resistant depression. This was a two-month study

involving patients who were on antidepressants that were not working. As with

the other omega-3 studies discussed, the fish oil was well tolerated and no

adverse events were reported.44

 

 

 

There is also evidence that omega-3 oils may be of benefit in treating

depressive symptoms outside of major depressive disorder. Canadian researchers

showed that Antarctic krill oil (400mg EPA, 240mg DHA) could improve depressive

symptoms associated with premenstrual syndrome.45 Harvard researchers have also

shown that just 1g of pure EPA is beneficial in the treatment of borderline

personality disorder. This personality disorder, which is particularly difficult

to treat, is characterized by both depressive and aggressive symptoms. This was

a two-month placebo-controlled study and the results showed that EPA has a

mood-regulating effect, improving both depression and aggression versus

placebo.46

 

 

 

To date, with one exception, all studies conducted on omega-3 fatty acids and

mood have had a positive outcome. The singular negative study examined pure DHA

in patients with depression. The results in the case showed that DHA alone was

no better than placebo in alleviating depressive symptoms.47

 

 

 

Conclusion

 

 

Although an influence of EPA and DHA on brain physiology and structure is

apparent, the precise mechanisms whereby omega-3 fatty acids may alleviate

depression remain unknown. The results of the clinical trials reinforce the

epidemiological and experimental studies, underscoring the importance of

adequate omega-3 intake in those with depression.

 

 

 

The long-term studies of fish oil supplements in the area of cardiovascular

health, some spanning three-plus years, have shown that they are safe and well

tolerated.48,49 Patients with depression or depressive symptoms should discuss

omega-3 fatty acids with their health care providers. While scientists continue

to unravel the neuropsychological influences of omega-3 fatty acids, it should

be recognized that they are not a substitute for appropriate mental health

evaluation and care.

 

 

 

Alan C. Logan is a naturopathic physician licensed in Connecticut. Valedictorian

of the Canadian College of Naturopathic Medicine, class of 2001, his recent

medline-indexed article “Neurobehavioral Aspects of Omega-3 Fatty Acids:

Possible Mechanisms and Therapeutic Value in Major Depression” is available to

medical professionals by writing to Dr. Logan at aclnd.

 

 

 

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