Omega-3s from fish are essential to brain function and health.
Omega-3 EPA and DHA abound in virtually every human cell, and in seafood … and DHA is by far the dominant fat in human brains, where it plays many essential roles.
Some, though not all, population studies link higher fish intake to lower risk of Alzheimer’s disease (AD) and other forms of dementia.
Importantly, there’s loads of evidence that omeg-3-rich diets delay brain aging and promote optimal brain function … as described in dozens of articles in the Omega-3s & Brain Health section of our news archive.
And the results of clinical trials testing omega-3s in people with mild cognitive impairment or age-related cognitive decline show measurable, albeit modest, improvements (Otaegui-Arrazola A et al. 2013).
In a study published last year, researchers showed that omega-3s prompt immune-system cells to absorb amyloid-beta protein, which forms a pro-inflammatory, cell killing plaque in Alzheimer's patients’ brains (Hjorth E et al. 2013).
Yet – surprisingly – most of the published clinical trials testing omega-3 supplements in patients with established Alzheimer’s disease have so far detected no significant benefits.
The exceptions include a few small clinical studies that found minor but measurable benefits … see “Omega-3 Fish Oil Aided Alzheimer’s Patients”, “Omega-3s Seen to Ease Alzheimer’s Symptoms”, and “Omega-3 DHA Alleviated Agitation in Early-Onset Alzheimer’s”.
Critically, researchers note that to date, most of the trials were rather short ... and that any benefit of omega-3s may be negated in the one-quarter of Alzheimer’s patients who carry the APOE4 gene variation and in those with other potent risk factors (Cederholm T et al. 2013).
These other risk factors include the standard American diet’s extreme excess of generally pro-inflammatory omega-6 fats, which hinder absorption of dietary omega-3s … see “Omega-3 Displays More Alzheimer’s-Deterring Effects: Omega-3/Omega-6 dietary ratio found a key factor”.
In light of the minor-to-negative clinical trial results seen so far, why should researchers keep testing omega-3 supplements?
For one thing, studies in rodents with Alzheimer’s showed that long-term intake of omega-3s reduced brain-cell death and the amyloid-beta plaque linked to the disease, while improving cognitive function (Hooijmans CR et al. 2012).
And in addition to improving poor vascular health – which is implicated in dementia – the body uses omega-3s to moderate and end the kind of chronic brain inflammation linked with Alzheimer’s disease, which is believed to promote and worsen the disease.
Also, as we reported four years ago, Alzheimer's patients apparently have difficulty making omega-3 DHA, which is critical to brain functions, so it’s been thought that supplemental DHA might help.
Now, research from Sweden provides more evidence of that difficulty making DHA … and found signs that the role of omega-3s (EPA and DHA) in resolving inflammation suggests that they might help prevent or delay Alzheimer’s and other forms of dementia.
However, it seems likely the promise of omega-3s is limited to delaying or (in some cases) preventing Alzheimer’s disease ... and only if a person's diet is rich in omega-3s for decades in advance of any obvious symptoms.
That hopeful hypothesis fits with newer evidence – such as findings from the famed "Nun's study" – showing that people display subtle verbal signs of higher risk decades before the onset of any symptoms.
Swedish study sees encouraging effects
As with other neurodegenerative diseases, Alzheimer's is characterized by chronic inflammation in the brain.
Prolonged inflammation, which provokes the release of inflammatory and toxic substances, can damage or kill neurons (brain cells).
The body uses omega-3 EPA and DHA to end or “resolve” inflammation when it is no longer needed for wound-healing or fighting infections … see “Aspirin Mimics a Fishy Omega-3”.
Specifically, EPA and DHA are used to make “specialized pro-resolving mediators” (SPMs), which prompt immune system cells to clear debris from dead cells and stimulate the release of growth factors that foster tissue repair.
Recent research from Sweden’s famed Karolinska Institute shows that patients with Alzheimer's disease may be unable to properly end inflammation in the brain (Wang X et al. 2014).
According to lead author Marianne Schultzberg, PhD, “Our hypothesis is that stimulation of resolution of inflammation in Alzheimer's disease may result in reduced neuronal (brain-cell) death in the brain, and in turn have a beneficial effect in disease progression and cognition.” (KI 2014)
Indeed, her team’s study showed that the brain and cerebrospinal fluid levels of omega-3s necessary for brain-tissue recovery – through clearance of harmful inflammatory substances – are lower than normal in patients with Alzheimer's disease.
The Karolinska group also found that these lower levels of omega-3s correlate with a lower degree of cognitive function … especially memory capacity.
Study examined brain tissue and spinal fluid from patients and health controls
The Karolinska team analyzed cerebrospinal fluid from 15 patients with Alzheimer's disease, 20 patients with mild cognitive impairment and 21 control subjects.
They also analyzed postmortem brain tissue taken from the hippocampus (memory center) of 10 Alzheimer's patients and 10 control subjects.
Their analysis showed that a key omega-3-mediated resolution pathway definitely exists in the brain, and they said that their findings “strongly suggest” a dysfunction of this pathway in Alzheimer’s disease.
Accordingly, the scientists suggested that omega-3 supplements may offer “a new and promising therapy in neurodegenerative disorders such as Alzheimer’s disease.” (Wang X et al. 2014)
We should note the results of a (short-term) study in patients with mild to moderate Alzheimer’s, which found that omega-3 supplements did not reduce inflammatory markers in their blood or cerebrospinal fluid (Freund-Levi Y et al. 2009).
The Swedish researchers are now investigating how inflammation-resolving omega-3s (EPA and DHA) affect brain-cell death.
And they’re probing whether diets rich in these seafood-source omega-3s can prevent brain degeneration and improve memory function in animals with an Alzheimer's-like disease.
Their research was funded with support from the Swedish Research Council, Swedish Brain Power, and various non-for-profit foundations not associated with omega-3 companies.
- Cederholm T, Salem N Jr, Palmblad J. ω-3 fatty acids in the prevention of cognitive decline in humans. Adv Nutr. 2013 Nov 6;4(6):672-6. doi: 10.3945/an.113.004556. eCollection 2013 Nov
- Freund-Levi Y, Hjorth E, Lindberg C, Cederholm T, Faxen-Irving G, Vedin I, Palmblad J, Wahlund LO, Schultzberg M, Basun H, Eriksdotter Jönhagen M. Effects of omega-3 fatty acids on inflammatory markers in cerebrospinal fluid and plasma in Alzheimer's disease: the OmegAD study. Dement Geriatr Cogn Disord. 2009;27(5):481-90. doi: 10.1159/000218081. Epub 2009 May 12.
- Hjorth E, Zhu M, Toro VC, Vedin I, Palmblad J, Cederholm T, Freund-Levi Y, Faxen-Irving G, Wahlund LO, Basun H, Eriksdotter M, Schultzberg M. Omega-3 fatty acids enhance phagocytosis of Alzheimer's disease-related amyloid-β42 by human microglia and decrease inflammatory markers. J Alzheimers Dis. 2013;35(4):697-713. doi: 10.3233/JAD-130131.
- Hooijmans CR, Pasker-de Jong PC, de Vries RB, Ritskes-Hoitinga M. The effects of long-term omega-3 fatty acid supplementation on cognition and Alzheimer's pathology in animal models of Alzheimer's disease: a systematic review and meta-analysis. J Alzheimers Dis. 2012;28(1):191-209. doi: 10.3233/JAD-2011-111217. Review.
- Otaegui-Arrazola A, Amiano P, Elbusto A, Urdaneta E, Martínez-Lage P. Diet, cognition, and Alzheimer's disease: food for thought. Eur J Nutr. 2014 Feb;53(1):1-23. doi: 10.1007/s00394-013-0561-3. Epub 2013 Jul 27.
- Wang X, Zhu M, Hjorth E, Cortés-Toro V, Eyjolfsdottir H, Graff C, Nennesmo I, Palmblad J, Eriksdotter M, Sambamurti K, Fitzgerald JM, Serhan CN, Granholm AC, Schultzberg M. Resolution of inflammation is altered in Alzheimer's disease. Alzheimers Dement. 2014 Feb 12. pii: S1552-5260(14)00030-2. doi: 10.1016/j.jalz.2013.12.024. [Epub ahead of print]