Findings hold new hope for effective Alzheimer’s treatment; human trials in progress
by Craig Weatherby
A growing body of evidence supports the old adage that “fish is brain food.” However, the matter is not fully settled, as shown by the opposing conclusions of two recent evidence reviews.
In 2005, researchers at RAND Health’s Southern California Evidence-Based Practice Center in Santa Monica, California analyzed the most relevant and well-designed studies regarding the effects of omega-3 fatty acids on measures of cognitive function in normal aging and rates of dementia (Issa M 2005).
As the RAND team concluded, “The available data are insufficient to draw strong conclusions … However, limited evidence suggests a possible association between omega-3 fatty acids and reduced risk of dementia.”
And, earlier this year, doctors in the geriatric department of Singapore’s Tan Tock Seng Hospital published their review of the available evidence that omega-3s might prevent cognitive impairment and dementia in mentally healthy seniors (Lim WS 2006). They intended to review the results of randomized, placebo-controlled, doubled blind studies lasting at least six months, but could find none that met these criteria.
As a result, the Singapore team could only come to an equivocal conclusion: “There is a growing body of evidence from biological, observational and epidemiological studies that suggests a protective effect of … [omega-3s] … against dementia. However, until data from randomized trials become available for analysis, there is no good evidence to support the use of dietary or supplemental [omega-3s] for the prevention of cognitive impairment or dementia.”
The results of two controlled clinical trials are expected in 2008, so we may have more definitive evidence then.
In the meantime, the results of an animal study conducted at the Massachusetts Institute of Technology offer encouraging evidence of the brain-health benefits of omega-3s. Such "mechanistic" studies, which seek to illuminate the mechanisms by which nutrients or drugs work at the cellular level, provide both credible evidence of likely benefit and the rationale for conducting the kind of controlled clinical studies in progress right now.
MIT results bolster hope for the brain benefits of omega-3s
Until very recently, the dominant hypothesis of Alzheimer’s disease was that the amyloid protein plaques and tangles seen in the brains of patients caused the disorder and patients’ dramatic cognitive declines.
But drugs and antioxidants that target amyloid protein plaques and tangles, while slightly effective in slowing the progression of dementia in Alzheimer's disease, have failed to produce the kind of substantial benefits one would expect if these rogue proteins were the cause of Alzheimer’s disease.
This failure has led researchers to propose that the dementia seen in Alzheimer's results not primarily from amyloid plaques and tangles, but instead from damage to synapses in the parts of the brain involved in learning and memory.
Earlier this month, Richard Wurtman, Distinguished Professor of Neuropharmacology at MIT, announced novel findings concerning the effects of omega-3s on the cell membranes that form synapses (Wurtman R 2006).
The MIT group fed gerbils a “cocktail” consisting of three natural bodily chemicals—omega-3 fatty acids, uridine and choline—essential to the body’s ability to make the phospholipids that constitute the primary component of cell membranes in the brain.
As hoped, the trio of supplements produced a large increase in the levels of brain proteins found within synapses, which indicates that more synaptic membranes had formed: an effect that allows messages to cross from one neuron (brain cell) to the next more readily and easily.
Dr. Wurtman believes that if these results are duplicated in placebo-controlled human trials currently underway at several medical centers, the omega-3/uridine/choline cocktail could ameliorate the effects of Alzheimer's as powerfully as the dopamine precursor L-dopa can alleviate the symptoms of Parkinson's disease and slow its progression.
Omega-3s alone strengthen synapses: trio adds synergistic benefits
While the most dramatic increase in membrane growth was observed in gerbils fed all three compounds, the levels of synaptic membrane protein levels rose significantly in gerbils given omega-3 fatty acids alone.
As Dr. Wurtman noted, "To my knowledge, this is the first concrete explanation for the behavioral effects of taking omega-3 fatty acids."
And last year, a French team found that treatment of rat neuroblastoma cells with omega-3s for three days significantly enhanced the length of these brain cells' neurites (Shrivastava R 2005).
The ability of omega-3s to increase synaptic membrane formation is backed by the results of recent studies by scientists at the National Institute on Alcohol Abuse and Alcoholism (Calderon F 2004)) China’s Nanjing University (Cao D 2005) and England’s Cambridge University (Darios F 2006), which showed that marine omega-3 called DHA can promote the growth of small outgrowths of neuronal cell membranes called neurites.
We’ll let you know what comes out of the clinical trials of omega-3s and the omega-3/choline/uridine cocktail when they are published, and we’ll keep our fingers crossed on behalf of everyone who has Alzheimer’s disease or is at risk of developing it.
How much omega-3 brain insurance should you take out?
In the meantime, given the generally positive findings of the studies conducted to date and the absence of serious side effects, it only makes sense to ensure that you are getting the recommended omega-3s into your diet.
Each 1000 mg capsule of Vital Choice sockeye salmon oil provides about 160 mg of the two key omega-3s (90 mg EPA and 70 mg DHA), so you would need to take two to four capsules per day to meet the guidelines set by the two scientific bodies with the greatest expertise in this area: the US Institute of Medicine (IOM) and the International Society for the Study of Fatty Acids and Lipids (ISSFAL).
Given that ISSFAL represents the most knowledgeable fatty acid researchers in the world, we think it makes more sense to rely on their recommendation, which is that adults of both genders should consume at least 660 mg of long-chain, marine-source omega-3s (EPA and DHA), which you can obtain by taking four capsules of our sockeye oil per day.
In contrast, one would only need to take two capsules per day to meet the IOM’s adequate daily intake level for women (260 mg) or three per day to meet the IOM recommendation for men (400 mg).
Note: If you take blood-thinning drugs or have a serious cardiovascular condition—especially a diagnosis of angina or an irregular heartbeat that involves use of an implantable cardioverter defibrillator (ICD)—check with your doctor before taking any omega-3 supplements. While omega-3s are proven to protect against heart attacks and strokes, they may be inadvisable in certain circumstances.
- Wurtman R, Ulus I, Cansev M, Watkins W, Wang L, Marzloff G. Increased dendritic spine density in adult gerbil hippocampus following oral UMP and DHA supplementation. The International Academy of Nutrition & Aging 2006 SYMPOSIUM II Nutrition and Alzheimer’s Disease/Cognitive Decline. Oral Presentation May 2, 2006, InterContinental Chicago.
- Wurtman RJ, Ulus IH, Cansev M, Watkins CJ, Wang L, Marzloff G. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Res. 2006 Apr 19; [Epub ahead of print]
- Darios F, Davletov B. Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3. Nature. 2006 Apr 6;440(7085):813-7.
- Shrivastava R, Vincent B, Gobron S, Cucuat N, John GW. Evidence for growth-promoting effects of omega n - 3 fatty acids alone and in combination with a specific vitamin and mineral complex in rat neuroblastoma cells. Nutr Neurosci. 2005 Oct-Dec;8(5-6):317-21.
- Marszalek JR, Lodish HF. Docosahexaenoic acid, fatty acid-interacting proteins, and neuronal function: breastmilk and fish are good for you. Annu Rev Cell Dev Biol. 2005;21:633-57. Review.
- Cao D, Xue R, Xu J, Liu Z. Effects of docosahexaenoic acid on the survival and neurite outgrowth of rat cortical neurons in primary cultures. J Nutr Biochem. 2005 Sep;16(9):538-46.
- Calderon F, Kim HY. Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem. 2004 Aug;90(4):979-88. Erratum in: J Neurochem. 2004 Sep;90(6):1540.
- Cansev M, Watkins CJ, van der Beek EM, Wurtman RJ. Oral uridine-5'-monophosphate (UMP) increases brain CDP-choline levels in gerbils. Brain Res. 2005 Oct 5;1058(1-2):101-8. Epub 2005 Aug 29.
- Wang L, Pooler AM, Albrecht MA, Wurtman RJ. Dietary uridine-5'-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats. J Mol Neurosci. 2005;27(1):137-45.
- Issa AM, Mojica WA, Morton SC, Traina S, Newberry SJ, Hilton LG, Garland RH, Maclean CH. The efficacy of omega-3 fatty acids on cognitive function in aging and dementia: a systematic review. Dement Geriatr Cogn Disord. 2006;21(2):88-96. Epub 2005 Dec 9. Review.
- Lim WS, Gammack JK, Van Niekerk J, Dangour AD. Omega 3 fatty acid for the prevention of dementia. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005379. Review.