National Alzheimers Disease Institute

 

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Alzheimer’s Disease

Omega-3 Fatty Acids (e.g. Fish Oil)

P. Anthony Chapdelaine, Jr., MD, MSPH, Exec. Dir./Sec.*

 

The NIH says this about fish oil/omega-3s: “Among the nutritional and dietary factors studied to prevent cognitive decline in older adults, the most consistent positive research findings are for omega-3 fatty acids, often measured as how much fish people ate. However, taking omega-3 supplements did not have any beneficial effects on the cognitive functioning of older people without dementia.”1

In stating their blanket dismissal of omega-3 fatty acids as being “not beneficial” in preventing cognitive decline in people with normal functioning brains, the NIH ignores a 2014 retrospective cohort study which it supported through multiple NIH Institutes and Centers along with support from a number of drug companies.2

That cohort study concluded that: “FOS [fish oil supplement] use during follow-up was associated with significantly lower mean cognitive subscale of the Alzheimer’s Disease Assessment Scale and higher Mini-Mental State Examination scores among those with normal cognition [emphasis added]. Associations between FOS use and the outcomes were observed only in APOE ε4-negative participants [emphasis added]. FOS use during the study was also associated with less atrophy in one or more brain regions of interest.”

There is now excellent evidence that sufficient omega-3 fatty acid, from fish or supplements, by itself can prevent or minimize the risk of Alzheimer’s Disease in people without the genetic marker APOE ε4 who do not currently have AD.

Results from a randomized, placebo-controlled, double-blind, multi-center studies presented at the 2009 International Conference on Alzheimer’s Disease in Vienna presented by the Alzheimer’s Association showed that supplementing patients with “probable” AD for eighteen months with DHA fatty acids, as expected, did not affect mental decline (although it appeared to slow cognitive decline in those patients who had the APOE ε4 gene).3

On the other hand, also presented at this 2009 Conference, were results of a six month study involving patients with normal, age-related, mild memory complaints, which showed that patients taking DHA had a healthier, decreased heart rate and an improvement in memory equivalent to a person three years younger! This was after only six months.4

William Thies, PhD, the chief medical and scientific officer for the Alzheimer’s Association concluded that, “These two studies raise the possibility that [interventions] for Alzheimer’s must be given very early in the disease for them to be truly effective.”

The NIH and a reference they quote, the Cochrane Review – in which two reviewers only looked at three controlled studies of people with mild to moderate AD (but not people without AD) – give the appearance of creating what in logic is known as a straw-man, which they proceed to knock down. Perhaps inadvertently, the reviewers set up a false target (a claim which nobody made in the first place) and then proceed to prove that “claim” is wrong. There is no claim that omega-3s will prevent or reverse existing AD (although no one knows what might happen after several decades of taking omega-3s because there are no prospective studies that have ever looked at that issue). The only claim being made is that omega-3s will help protect people from cognitive decline who don’t have the genetic marker APOE ε4 (less than one-out-of-a-thousand patients who have AD!) and also don’t have AD.

In other words, most people who don’t have AD to begin with will likely find a degree of protection from AD by the consistent consumption of adequate omega-3 fatty acids!

This Cochrane Review of three studies is typical for academic medicine and the NIH, as illustrated by another study presented at the International Conference on Alzheimer’s Disease quoted above3, which was later published in JAMA in 2010, and which looked at mild to moderate AD and concluded that fish oil did not prevent cognitive decline over eighteen months.5 However, these researchers did not study, or know, whether omega-3 would prevent such decline in healthy adults who take the fish oils over many years or decades.

A pair of studies conducted by the Dutch National Institute for Public Health and the Environment and researchers at the University of North Carolina that was published in the American Journal of Clinical Nutrition in 2007 pointed out that very few studies had ever been done to determine the effect of omega-3 fatty acids on preventing cognitive decline in older normal patients with mild cognitive impairment. They concluded that for these people, but not for people with mild to moderate AD, omega-3 fatty acids do prevent age-related cognitive decline. Drawing on these studies, researchers at Taipei City Hospital (Taiwan) had a group of participants with mild to moderate AD and another group with mild cognitive decline randomized to taking daily fish oil or placebo for six months. The results were clear: the fish oil helped all participants’ general clinical function compared with placebo, but did not help cognitive decline in AD; however, omega-3 fatty acids did slow down the decline in cognitive function for people with mild cognitive impairment.6

Results from a prospective cohort study of over 8000 non-demented participants age 65 or over in three French Cities in 2009 and 2000, in which there was at least one re-examination over the next four years, were reviewed by an independent panel of neurologists, which determined there were 281 cases of dementia (183 were considered Alzheimer’s Disease).7 (This study may be found also at the NIH website.)

Daily consumption of fruits and vegetables decreased the overall dementia rate.

Eating fish weekly decreased the incidence of having Alzheimer’s Disease (but only among those who did not have the APOE ε4 gene) and also decreased the likelihood of having any type of dementia.

Those participants who used omega-3 oils regularly showed a marginal decrease for any kind of dementia.

Our conclusions must be that fish oils must be started early, before significant cognitive decline appears, if there is to be a protective effect among elderly people; that omega-3 oils can have a positive effect in preventing at least some AD, but only in those without the APOE ε4 gene (a minority of people); that consuming fruits and vegetables consistently (organic when possible) contributes to protection from cognitive decline, including AD.

What About the EPA Part of Omega-3 Fatty Acids?

There is evidence supporting the use of EPA (EPA and DHA are major components of fish oil) in improving memory and learning in rats, reducing the risk of Alzheimer’s Disease. A study by researchers from Canada and Thailand published in the Journal of Neurochemistry in 2010 looked at acetylcholine release and “growth factor” expression in the rat brain’s hippocampus, both of these factors being linked to memory deficits when the brain’s acetylcholine neurotransmitter decreases with age.8 The EPA-fed rats, compared with the controls, showed a decrease in acetylcholine release and growth factor expression (in other words, showed a decrease in the loss of acetylcholine) and showed an improvement in memory.

This is an important clue to one of the factors involved in AD, one which likely holds true in humans as well.

Thus one more reason to supplement with omega-3 fatty acids.

What About Alpha-Lipoic Acid and Omega-3 Fatty Acids?

In three lab experiments completed in 2008, researchers made an interesting discovery, showing that Alpha-lipoic acid “can potently inhibit peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation,” two contributors to neurodegenerative diseases, including Alzheimer’s Disease.9

What makes this so interesting is that a small double-blind, placebo-controlled study of 39 individuals with AD, published in 2014, showed that the study participants who took a combination of a small dose of alpha-lipoic acid and omega-3 fatty acids were able to slow their cognitive decline over the year of the study.10 Omega-3 fatty acids (fish oil) alone did not slow cognitive decline, which is consistent with other studies as we have already discussed, since the fish oils only seem to work as a preventive (i.e. before AD symptoms manifest). Now we have a mechanism to help explain some of alpha-lipoic acid’s protection from cognitive decline in AD patients: the inhibition of peroxynitrite-mediated DNA genetic damage and inhibition of hydroxyl radical formation.

Note that the alpha-lipoic acid used in this small study was the racemic (mixed) form, not the pure d-alpha-lipoic acid form. Racemic lipoic acid has been shown to be inferior to alpha-lipoic acid. The racemic dose of 600 mg given in the study is functionally much less than half that of the more effective d-alpha lipoic acid. Nonetheless, even the inadequate dose used in this study, when combined with the omega-3 fatty acid, showed some protection against cognitive decline over the course of a year for AD participants.

Bottom Line

Thomas Shea, PhD and colleagues at the University of Massachusetts have conducted many years of laboratory and clinical research on cognitive and neuro degeneration. They have concluded that AD arises from a combination of factors, including genetics, poor diet, and environmental factors, none of which alone would typically cause the disease, and as they state:

“Overall consideration of the most recent collective evidence suggests that the optimal approach for Alzheimer’s disease would seem to combine early, multicomponent nutritional approaches (a Mediterranean-style diet, multivitamins and key combinatorial supplements), along with lifestyle modifications such as social activity and mental and physical exercise, with ultimate addition of pharmacological agents when warranted.”11

Ignore the current NIH recommendations and take concentrated omega-3 fish oil capsules from a reputable source. Also, a reputable multivitamin with d-alpha-lipoic acid and a decent supply of mixed natural vitamin E and buffered vitamin C. Eat fruits and vegetables daily. Exercise (moderately as tolerated, which can be walking) at least 20 minutes daily. Spend time with family and friends. Avoid toxins from food, pesticide use, exposure to heavy metals in your drinking or food supply.

 

* The National Alzheimer’s Disease Institute is a project of The National Fund for Alternative Medicine

 

References/Sources

  1. https://nccih.nih.gov/health/alzheimer/ataglance
  2. Daiello LA, Gongvatana A, et al, “Association of Fish Oil Supplement Use with Preservation of Brain Volume and Cognitive Function,” Alzheimer’s Dement, 2015, 11(2), Pgs 226-235, doi:10.1016/j.jalz.2014.02.005.
  3. Quinn JF, Raman R, et al, “A Clinical Trial of Docosahexanoic Acid (DHA) for the Treatment of Alzheimer’s Disease,” Presentation #O1-04-02, 12 July 2009, Alzheimer’s Association 2009 International Conference on Alzheimer’s Disease (ICAD 2009) in Vienna.
  4. Yurko-Mauro K, McCarthy D, et al, “Results of the MIDAS Trial: Effects of Docosahexaenoic Acid on Physiological and Safety Parameters in Age-Related Cognitive Decline,” Presentation #O1-04-01, 12 July 2009, Alzheimer’s Association 2009 International Conference on Alzheimer’s Disease (ICAD 2009) in Vienna.
  5. Quinn JF, Raman R, et al, “Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease: A Randomized Trial,” JAMA, 2010, 304(17), Pgs 1903-1911.
  6. Chiu CC, Su KP, et al, The Effects of Omega-3 Fatty Acids Monotherapy In Alzheimer’s Disease and Mild Cognitive Impairment: A Preliminary Randomized Double-blind Placebo-controlled Study,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2008, 32(6), Pgs 1538-1544.
  7. Barberger-Gateau P, Raffaitin C, et al, “Dietary Patterns and Risk of Dementia: the Three-City Cohort,” Neurology, 2007, 69(20), Pgs. 1921-1930.
  8. Taepavarapruk P, Song C, “Reductions of Acetylcholine Release and Nerve Growth Factor Expression Are Correlated with Memory Impairment Induced by Interleukin-1beta Administrations: Effects of Omega-3 Fatty and EPA Treatment,” Journal of Neurochemistry, 2010, 112(4), Pgs 1054-1064.
  9. Jia Z, Zhu H, et al, “Alpha-lipoic Acid Potently Inhibits Peroxynitrite-mediated DNA Strand Breakage and Hydroxyl Radical Formation: Implications for the Neuroprotective Effects of Alpha-lipoic Acid,” Mol Cell Biochem, 2009, 323(1-2), Pgs 131-138, doi: 10.1007/s11010-008-9971-6.
  10. Shinto L, Quinn J, et al, “A Randomized Placebo-Controlled Pilot Trial of Omega-3 Fatty Acids and Alpha Lipoic Acid in Alzheimer’s Disease,” J Alzheimers Dis, 2014, 38(1), doi: 10.3233/JAD-130722.
  11. Shea TB, Remington R, “Nutritonal Supplementation for Alzheimer’s Disease?” Curr Opin Psychiatry, 2015, Mar 28(2), Pgs 141-147, doi: 10.1097/YCO.0000000000000138.