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Dr. Sears' Blog

Breaking down the latest research on Anti-Inflammatory Nutrition
Written By: Dr. Barry Sears, Ph. D | Creator of the Zone Diet

Written by Dr. Barry Sears
on February 09, 2016

A recent study published in JAMA indicated that eating more fish appears to reduce the probability of developing Alzheimer’s. However, that association was only significant for those individuals with high ApoE4 levels in the blood.

What is ApoE4? It’s protein that’s an integral part of circulating lipoproteins.

What’s the connection with Alzheimer’s? Those individuals who have a certain genetic mutant of this protein (know as ApoE4) are at much higher risk for developing Alzheimer’s. In fact, about 14 times higher. That’s a lot, but why? And what do levels of lipoproteins high in ApoE have to do with Alzheimer’s?

With Fish Oil, It’s Easier to Fight Alzheimer’s

In the past, lipoproteins (like LDL or bad cholesterol) were usually associated only with heart disease. The first insight of the relationship with Alzheimer’s comes with a recent study that indicated those with high levels of ApoE4 in their lipoproteins have difficulty in transferring omega-3 fatty acids into the brain. Without adequate levels of omega-3 fatty acids being supplied to the brain, you will have a limited chance to reduce neuroinflammation that is the underlying cause of Alzheimer’s. This explains why it was only in the subjects that had high levels of ApoE4 had any benefits by consuming more fish in reducing the development of Alzheimer’s.

And here’s another important point that seems to be lost on Alzheimer’s researchers: there is a big difference between the anti-inflammatory actions of omega-3 fatty acids and the pro-resolution activity of the same fatty acids.

The resolution of inflammation remains the Holy Grail of medicine because it is only this resolution response that brings the inflammatory response back to equilibrium. However, the resolution response can only be optimized with adequate levels of EPA and DHA in diet in order to supply the building blocks to make the pro-resolution hormones known as resolvins.

Even more importantly, the key fatty acid for resolution in the brain appears to be EPA, not DHA.

Don’t Forget: You Need EPA in Your Blood

You need EPA in your blood to make pro-resolution hormones. The best marker for your ability to resolve inflammation is the AA/EPA ratio. This was supported in a study that demonstrated that AA/EPA ratio in both Alzheimer’s patients and cognitively impaired patients was significantly elevated compared to age-matched subjects with normal cognitive functioning.

That observation from 16 years ago was extended by recent work demonstrating the resolution response in older individuals is reduced. The only way to increase that resolution response regardless of age is to increase your intake of EPA and DHA

Brain Trauma: It’s Like an Accelerated Form of Alzheimer’s

I view severe brain trauma as an accelerated form of Alzheimer’s. I demonstrated several years ago in animal studies that giving high-dose omega-3 fatty acids would reduce the production of amyloid precursor proteins (APP) in the brain induced by severe head trauma.

Appearance of APP in the brain is the first step toward the development of an Alzheimer’s plaque in the brain. As I demonstrated in that article, the blood marker that was the best correlated with the reduction of APP formation was a reduced AA/EPA ratio.

Applying the same protocol to humans with severe brain trauma has shown when you reduce the AA/EPA ratio to less than two, then seemingly “miraculous” recoveries become commonplace.

Danger: Fish vs. Fish Oil

One of the problems of consuming adequate levels of fish to generate the resolution benefits from omega-3 fatty acids is that all fish contain some levels of a known neurotoxin called poly chlorinated biphenyls (PCBs). PCBs are known neurotoxins. So eating a lot of fish to reduce neuroinflammation may have unintended consequences like increased PCB levels.

This problem can be overcome by supplementing with purified omega-3 supplements, but only if they are suitable for long-term use. This is because omega-3 fatty acids have to be consumed at levels sufficient to induce a sufficient resolution response.

This is why Zone Labs is the only company that provides the levels of PCBs in every lot we sell. There are general industry standards for max PCB levels, and then there are Zone Labs standards on max PCB levels, which are nearly 20 times lower.

You need adequate levels of omega-3 fatty acids to achieve adequate blood levels of omega-3 fatty acids necessary to promote resolution of neuroinflammation in the brain.

Don’t Guess, Test Your Blood

How do you know if you are taking enough? The blood will tell you. In other words, “don’t guess, always test.” Your goal is achieve an AA/EPA ratio between 1.5 and 3. There are several sources for such testing that requires only a drop of blood. I recommend you try the most inexpensive source to test your blood through Zone Diagnostics.

Are higher intakes of omega-3 fatty acids your only dietary approach to reduce the likelihood of Alzheimer’s? Not by a long shot. Recent studies by the same authors of the recent article on fish oil and Alzheimer’s published a study on the ability of the MIND diet to reduce Alzheimer’s.

What is the MIND diet? It is simply the DASH diet with extra polyphenols, especially those coming from blueberries. Furthermore, high levels of purified cocoa polyphenols also have demonstrated the ability to improve cognitive function. The hypothesized mechanism for polyphenols is their reduction of insulin resistance.

Reduce Your Risk and Improve Your Odds

If you want to reduce the likelihood of developing Alzheimer’s, your best choice is to follow an anti-inflammatory diet such as the Zone Diet. Then, supplement that anti-inflammatory diet with refined omega-3 fatty acids and polyphenols.

How do you determine your success? Make sure you are in the Zone. The blood will tell you that with precision. As I described in The Mediterranean Zone, the clinical markers you are looking to achieve are the following:

  1. AA/EPA ratio between 1.5 and 3
  2. TG/HDL ratio less then 1
  3. Glycosylated hemoglobin (HbA1c) of 5.0%

This is not a multiple-choice test. All of these clinical markers have to be in the correct ranges or you are simply not in the Zone. If your blood says you aren’t in the Zone, then maybe you will be lucky when it comes to developing Alzheimer’s. Personally, I would rather be in the Zone than simply hoping to be lucky.New call-to-action References:

  1. Morris MC, Brockman J, Schneider JA, Wang Y, Bennett DA, Tangney CC, van de Rest O. “Association of seafood consumption, brain mercury level, and APOEε4 status with brain neuropathology in older adults.” JAMA 315:489-497 (2016).
  2. Vandal M, Alata W, Tremblay C, Rioux-Perreault C, Salem N, Calon F, and Plourde M. “Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2.” J Neurochem 129:516-526 (2014).
  3. Georgiou T, Neokleous A, Nikolaou D, and Sears B. "Pilot study for treating dry age-related macular degeneration (AMD) with high-dose omega-3 fatty acids.” PharmaNutrition 2:8-11 (2014).
  4. Conquer JA, Tierney MC, Zecevic J, Bettger WJ, and Fisher RH. “Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment.” Lipids 35:1305-1312 (2000).
  5. Wang X, Zhu M, Hjorth E, Cortes-Toro V, Eyjolfsdottir H, Graff C, Nennesmo I, Palmblad J, Eriksdotter M, Sambamurti K, Fitzgerald JM, Serhan CN, Granholm AC, and Schultzberg M. “Resolution of inflammation is altered in Alzheimer's disease.” Alzheimers Dement 11:40-50.e2 (2015).
  6. Mills JD, Bailes JE, Sedney CL, Hutchins H, and Sears B. “Omega-3 dietary supplementation reduces traumatic axonal injury in a rodent head injury model.” J Neurosurgery 114:77-84 (2011).
  7. Sears B, Bailes J, and Asselin B. “Therapeutic uses of high-dose omega-3 fatty acids to treat comatose patients with severe brain injury.” PharmaNutrition 1: 86-89 (2013).
  8. Morris MC, Tangney CC, Wang Y, Sacks FM, Bennett DA, and Aggarwal NT. “MIND diet associated with reduced incidence of Alzheimer's disease.” Alzheimers Dement 11:1007-1014 (2015).
  9. Mastroiacovo D, Kwik-Uribe C, Grassi D, Necozione S, Raffaele A, Pistacchio L, Righetti R, Bocale R, Lechiara MC, Marini C, Ferri C, and Desideri G. “Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects.” Am J Clin Nutr 101:538-548 (2015).
  10. Sears, B. The Mediterranean Zone. Ballantine Books. New York, NY (2014).

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