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Three New Studies Bolster Mood Benefits of Omega-3s
6/12/2006
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Leading psychiatric journal publishes positive evidence review regarding anti-depression benefits of omega-3s; positive preliminary research in childhood depression and adult suicide risk
by Craig Weatherby


The effect of omega-3 fatty acids on mood took center stage this month, when the June issue of the American Journal of Psychiatry featured the positive results of three studies exploring aspects of a subject highly relevant to public health.

These findings add to the considerable body of evidence that supports the widely hypothesized association between mood disorders and three negative characteristics common to diets in developed countries:
  • Inadequate intake of omega-3s;
  • Correspondingly low tissue levels of omega-3s;
  • Excessive intake of omega-6 fatty acids, which compete with dietary omega-3s for inclusion in cell walls and influence on the metabolic pathways that exert profound effects on the myriad internal and external factors associated with all of the major degenerative diseases.
The Three Studies, in Brief
  • In a small clinical trial in depressed children aged 6-12 years, only those who received fish oil supplements enjoyed a major drop in depression.

  • A two-year pilot cohort study involving 30 suicide-prone psychiatric patients indicates that either low tissue levels of the omega-3 fatty acid DHA or a high ratio of omega-6 to omega-3 fatty acids predicts increased risk of suicide.

  • A new evidence review confirms that higher omega-3 intake can alleviate depression in people with low intake of omega-3s and excessive intake of omega-6 fatty acids. More research is needed on bipolar disorder and postpartum depression.
Study 1: Omega-3s may alleviate childhood depression
Some three percent of prepubescent children suffer from major depression: a small proportion that nonetheless adds up hundreds of thousands of miserable kids and even greater numbers of desperate parents and care givers.

Clinical studies in adolescent children indicate that about half receive some relief from treatment with either selective serotonin reuptake inhibitors (e.g., Prozac, Zoloft) or placebo pills.

However, these potent psychotropic drugs are not without their risks, and the efficacy of drug or nutrient treatment of prepubescent children is unknown. As the authors of this study said, “Major depressive disorder in children may be more common than previously thought, and its therapeutics are unclear.”

The authors had experienced success in a previous study testing the effects of omega-3s in depressed adults, so they decided to conduct a small “pilot” study in children between the ages of 6 and 12, to see whether omega-3s might help children as well.

The trial was conducted in Israel, at child psychiatry clinics in the Medical Center of Israel and the Beer-Sheva Mental Health Center. The researchers recruited 28 children, 20 of whom completed enough of the 16-week study for their data to be included.

Evaluations of the children’s status were made at the start and end of the study and at three points between. The Israeli team used two kinds of evaluation tools: tests administered and graded by the doctors, and self-evaluations done by the children.

Each child received 1,000 mg of fish oil daily, either in one dose or in two 500 mg doses, depending on their ability to swallow a larger capsule. The 1,000 mg fish oil capsules contained 400 mg of EPA and 200 mg of DHA. Combined, the two 500 mg fish oil capsules supplied slightly smaller amounts of omega-3s (380 mg of EPA and 180 mg of DHA).

The active and placebo capsules were identical except for a slight difference in color, which could be distinguished only by an experienced observer able to compare them simultaneously, and no child reported a fishy taste when asked specifically.

And as the graph above shows, the results were very encouraging: the depression-rating scores of the children who took the fish oil capsules dropped by 50 percent, while almost no positive effect was detected in the children taking the placebo capsules.

The Israelis came to these positive conclusions:
  • “The effect of omega-3 is highly significant. Among the children on omega-3 treatment, seven out of 10 had a greater than 50% reduction in CDRS [Childhood Depression Rating Scale test] scores. Of those on placebo, zero out of 10 had a greater than 50% reduction in CDRS scores ….”

  • “Four out of 10 children in the omega-3 group met the remission criteria of … a CDRS score [of less than] <29 at study exit; no subject in the placebo group met this criteria …”

  • “The self-rating CDI [Childhood Depression Inventory test] results were similar … CGI [Clinical Global Impression test] results were also highly significant.

  • “There were no clinically relevant side effects reported.”
This small, preliminary study holds strong promise that omega-3s might provide a safe adjunct treatment for depressed children, and its findings warrant further testing in a larger trial.

Study 2: Evidence for fish fats evaluated in three major mood disorders

The authors of this evidence review (Parker G 2006) hail from Australia’s Prince of Wales Hospital. They examined current evidence concerning the effect of dietary omega-3s on three common mood disorders: 1) depression (moderate to severe); 2) bipolar disorder (i.e., manic–depression); and 3) postpartum depression.

Rather than a formal statistical examination (i.e., meta-analysis), the Australian team sought only to detect general trends and identify data gaps. In addition to their generally positive conclusions, the authors call for studies designed to determine which omega-3 fatty acid—EPA or DHA—provides the greatest mood-enhancing benefit.

We’ve summarized their findings with regard to three mood disorders:

Depression: strong evidence of benefit
Several months before the current evidence review, the authors of another evidence review (Sontrop J 2005) had this to say about omega-3s and depression: “The relationship between ... [omega-3s] ... and depression is biologically plausible and is consistent across study designs, study groups, and diverse populations, which increases the likelihood of a causal relationship.”

Likewise, the authors of the current review (Parker G 2006) concluded that most evidence shows omega-3s can exert therapeutic effects in depressed people, and that higher seafood consumption and higher tissue levels of fish-borne omega-3s yield reduced rates of mood disorders.

While they identified one recent clinical study in which supplemental omega-3s produced no apparent positive effect on depression (Hakkarainen R 2004), they noted two likely reasons for this unusual failure, and proposed an intriguing explanation related to the successful outcome of a Finnish omega-3/depression study in women (Timonen M 2004):
  • The subjects’ intake of EPA and DHA—the long-chain omega-3s used and found effective in almost all depression studies—was less than 0.5 grams (500 mg) per day (experts recommend getting at least 660 mg per day);

  • Most of the omega-3 fatty acids consumed by the men in this negative study was alpha-linolenic acid; the form found in plants, only 5–15 percent of which gets converted into the long-chain “marine” forms essential to brain function (EPA and DHA).

  • The negative findings of this male-only cohort study could be related to gender, since the results of a recent study in Finland showed that low fish consumption was only associated with depression in women. The Finns’ finding may mark the discovery of a distinction in the two gender’s degree of need for dietary omega-3s vis-à-vis depression-prevention. (The Australian evidence-reviewers noted that these results could indicate differences in the ways the two genders metabolize neurotransmitters and phospholipids.)
Bipolar Disorder (manic-depression): possibility of benefit; more study needed
The evidence with regard to this disorder—in which patients swing from depressed to hyperactive “manic” states—is less abundant and less clear than for “regular” depression. The results of two studies indicate that omega-3 supplements may help patients with bipolar disorder, but it remains to seen whether these possible benefits stem from some mood-stabilizing propensity of omega-3s or simply from their documented anti-depressant effect.

Postpartum Depression: mixed evidence; plausible rationale; more study needed
While the worldwide average rate of postpartum depression is 12.4 percent, national rates vary nearly 50-fold, from just 0.5 percent of mothers in affluent, seafood-loving Singapore to a horrifically high 24.5 percent of mothers in poverty-stricken South Africa.

We’ve reported the mixed results of small, “pilot” clinical trials that sought to determine the preventive effect of dietary omega-3s (see “New Study Supports Omega-3 Therapy in Post-Partum Depression”).

The authors of the current review note two things:
  1. Studies in women and animals indicate that it is safe for them to take omega-3 supplements during pregnancy and the postpartum period;

  2. The results of a cross-national analysis by leading clinician and omega-3 researcher Joe Hibbeln, M.D. (Hibbeln JR 2002) show that both higher seafood consumption and higher DHA content in the mothers’ breast milk predicted a lower risk of postpartum depression, and that higher reported seafood consumption predicted a higher DHA content in the mothers’ milk.
The Australian evidence-review team noted that omega-3 intake is likely to play a role in postpartum depression since, during the third trimester, the fetus accumulates an average of 67 mg of DHA per day, which is more than many women consume from fish or supplements (Innis SM 2003). For such women, transfer of DHA to the baby through the placenta and breast milk poses a risk of significant depletion of their own omega-3s during pregnancy and nursing, which could raise their risk of postpartum depression.

Study 3: Higher omega-3 tissue levels may reduce suicide attempts
Psychiatrist and omega-3 researcher Joe Hibbeln, M.D. is Chief of the Outpatient Clinic in the Laboratory of Clinical Studies at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland. We had the opportunity to hear him speak, and then speak with him at length, during last year’s Seafood & Health conference and at Dr. Andrew Weil’s Nutrition & Health conference in March of this year.

One of the studies published in the June issue of the American Journal of Psychiatry—which took place in Dr. Hibbeln’s clinic—compared the relationship between the tissue levels of omega-3s in seriously depressed patients and the rate at which they attempted suicide.

Dr. Hibbeln’s team recruited 33 adults seeking treatment for major depression who were free of any neurological or medical disease or substance dependence and were off antidepressant medications for at least 14 days prior to the start of the study.

His clinic has a reputation for suicide research and treatment of suicidal patients and attracts a high proportion of suicide attempters. Just over half of the subjects had a history of previous suicide attempt, and upon admission, most had failed recent depression treatment.

At the outset, the subjects’ blood levels of omega-3s (EPA and DHA) and the ratios of omega-6 to omega-3 fatty acids in their blood were recorded. The volunteers received inpatient (8 weeks) or outpatient (6 months) treatment from the research team, followed by community-based treatment.

Evaluations were performed at three, 12, and 24 months (by raters unaware of the subjects’ omega-3 status), with "time-to-subsequent-suicide-attempt" as the outcome against which the suicide-prevention power of higher blood levels of omega-3s would be measured. In addition, the results were adjusted to account for any medications prescribed during the follow-up period, and the subjects’ individual attributes.

Three of the 33 subjects dropped out, 23 did not attempt suicide, and seven made at least one suicide attempt, of which two were fatal.

As the research team concluded, “Lower docosahexaenoic acid [omega-3 DHA] percentages of total phospholipid fatty acids [i.e., tissue concentrations of DHA] … and higher omega-6/omega-3 ratio predicted subsequent suicide attempts …”

That is, with all other factors being equal, the subjects with the lowest blood levels of omega-3 DHA were the quickest to attempt suicide.

In addition, the subjects’ fatty acid status predicted the "time-to-subsequent-suicide-attempt" period, regardless of treatment with drugs or other therapies. In other words, the effects of low DHA blood levels or high omega-6/omega-3 ratios with regard to the main outcome measure—time to suicide attempt—were not altered by adjusting for the number of medications prescribed during the follow-up period.

Sources
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