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Omega-3 DHA Alleviates Agitation in Early-Onset Alzheimer’s
Omega-3 DHA found to reduce agitation among carriers of early-onset gene, and depression among other patients
12/3/2007by Craig Weatherby
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Last year, scientists at Sweden's widely respected Karolinska Institute reported positive results from the first controlled clinical trial of omega-3 fish oil supplements in people diagnosed with various stages of Alzheimer’s disease (See “Fish Oil May Halt Memory Decline in Alzheimer's”).

That study indicated that while supplemental omega-3s may be able to slow mental decline in people at early stages of Alzheimer’s, these fish fats probably can’t do much to slow mental decline substantially in people who are already at moderate to severe stages of the mind-destroying disease.

As they said in their 2006 report, diets high in omega-3s can help deter Alzheimer’s disease:

“Combined data from… epidemiologic [population-and-diet] studies point to preventive effects from long-term fish intake. Those results and the results from the present study support the idea that omega-3 fatty acids have a role in primary prevention of AD but not in treatment of manifest disease.” (Freund-Levi Y et al 2006)

The Swedes also noted that Alzheimer’s is characterized by inflammation in the brain and that omega-3s exert anti-inflammatory effects.

But by the time Alzheimer’s symptoms appear, the damage caused in patients’ brains by accumulation of amyloid protein plaque and nerve “tangles” is probably too advanced for symptoms to be alleviated much by anti-inflammatory drugs like aspirin or by anti-inflammatory food factors such as omega-3s and food-borne antioxidants.

As the Swedes wrote in 2006, there seems to be a critical period, two or more years before the onset of dementia, during which levels of inflammatory chemicals are elevated in the brains of people with mild to moderate AD.

Before or during this two-year pre-symptom window, omega-3s and other anti-inflammatory food factors – such as curcumin (from turmeric) or fellow polyphenols found in tea, berries, cherries, grapes, cocoa, and other antioxidant-rich foods – could help slow the advance of the disease.

Omega-3 DHA may target early-onset gene

Now, the same research team, led by Yvonne Freund-Levi, M.D., has reported the results of a second controlled clinical trial.

Their goal was to test the effects of marine omega-3s on people with various genetic profiles, including one associated with early onset of Alzheimer’s disease (AD).

Mental performance declines naturally with age, but genetics play a part in the complex progression of Alzheimer’s.

People with a gene that codes for a fat-protein compound in the blood called apolipoprotein E4 (ApoE4) tend to develop Alzheimer's disease at an earlier age, compared with people bearing the ApoE2 or ApoE3 gene.

The Swedes recruited 204 Alzheimer's patients (aged 65 to 83), all of whom were taking anti-Alzheimer’s drugs – acetylcholinesterase inhibitors such as Aricept, Exelon, and Razadyne. (These drugs do not cure Alzheimer's, but may delay cognitive decline and reduce behavioral problems.)

As in the clinical trial published in 2006, they gave some patients a fish oil supplement high in omega-3 DHA and low in omega-3 EPA.

(Most medical studies, except this team’s prior study in Alzheimer’s patients, employ standard fish oil supplements, that, like whole fish, contain significantly more omega-3 EPA than DHA.)

The Swedish team drew blood to determine which kind of ApoE genes each participant had: ApoE2, ApoE3, or the ApoE4 gene linked to high risk of early onset Alzheimer’s.

Then they divided the participants randomly into test (omega-3) and control (placebo) groups, with the test group slated to receive supplements containing 1.7 grams of DHA and 0.6 grams of EPA every day for six months.

After this initial six-month period, all of the participants in both groups took DHA-rich omega-3 supplements during a subsequent six-month stage of the study.

Results show greatest benefit for carriers of early onset gene

Overall, the outcomes showed no substantial difference between the patients receiving the omega-3 supplement and the placebo group.

However, when the researchers looked at the subgroup bearing the ApoE4 gene, the ones who’d received the omega-3 DHA supplement showed reduced agitation symptoms.

And the patients who bore the late-onset genes (ApoE2 or ApoE3) showed improvement in symptoms of depression.

As they wrote, “Supplementation with omega-3 in patients with mild to moderate AD … [showed] … possible positive effects on depressive symptoms in non-APOE4 carriers and agitation symptoms in APOE4 carriers.” (Freund-Levi Y et al 2007)

The Swedish authors observed no marked anti-inflammatory effects among the patients taking omega-3s.

It seems plausible to hypothesize that omega-3s may work at a more fundamental level, since we know that they affect the activation of cellular genetic switches called nuclear transcription factors.

While these switches influence the onset or cessation of inflammation, they have broader impacts as well, many of which likely remain to be discovered.


  • Freund-Levi Y, Basun H, Cederholm T, Faxen-Irving G, Garlind A, Grut M, Vedin I, Palmblad J, Wahlund LO, Eriksdotter-Jonhagen M. Omega-3 supplementation in mild to moderate Alzheimer's disease: effects on neuropsychiatric symptoms. Int J Geriatr Psychiatry. 2007 Jun 21; [Epub ahead of print]
  • Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol. 2006 Oct;63(10):1402-8.
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