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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 June 21, 2016

Recently, the National Center for Health Statistics announced that death rates in America are increasing for the first time in a decade. The biggest increase in deaths was 15% from Alzheimer’s disease.  Find out the real cause of Alzheimer’s disease and what you can do to prevent it using the Zone.

Our “war” on cancer seems like a victory compared to our pathetic results combating Alzheimer’s. In fact, both “wars” are going nowhere since we often concentrate on defending old theories instead of thinking outside the box. This is especially true in Alzheimer’s where the prevailing theory has been that amyloid plaques, which are clusters of proteins that develop between the nerve cells of the brain, cause Alzheimer’s disease. But what if that theory is wrong? Then billions of dollars in research and equal amounts in drug development studies may have been wasted.

Challenging the Theories on the Cause of Alzheimer’s

What is known about Alzheimer’s disease is that it's associated with aging, inflammation, and the ApoE4 genotype which is a risk factor for developing late onset Alzheimer's. Meanwhile, the amyloid plaque hypothesis remains popular, even though clinical data that suggests the causal relationship of amyloid plaques with the loss of mental cognition is not that strong 1-3.

New evidence suggests that amyloid plaque formation may be initially a protection mechanism to prevent microbial invasion in the brain 4. Unlike the rest of the organs in the body where white cells in the blood are transformed into killer cells (neutrophils and macrophages) that can enter the infected area to destroy microbial invasion, the brain is relatively isolated by the blood-brain barrier (BBB). Therefore, the brain relies on Plan B: the formation of a sticky cage built of beta amyloid proteins to trap the microbe so it eventually dies. The cage that is left behind is the amyloid plaque. This hypothesis is in line with new research that shows the BBB is leakier in Alzheimer’s patients than in age-matched normal subjects 5.

Inflammation May Be the Real Cause of Alzheimer’s

So where does inflammation and ApoE4 enter this picture? Inflammation must balance with resolution to maintain wellness.

Evidence supports that a faulty resolution response in Alzheimer’s is caused by a lack of resolution6 which is usually a consequence of inadequate levels of omega-3 fatty acids to produce the hormones known as resolvins. This ties in nicely with the ApoE connection. This particular protein controls the flow of omega-3 fatty acids into the brain. Those individuals who have an ApoE4 mutation, meaning that the resolution of inflammation caused by the debris of the dying microbe trapped within the amyloid plaque cage in the brain is compromised7, have microbial debris that remains a constant source of inflammation that eventually causes the death of brain cells.

How to Resolve Inflammation in the Brain

So what can you do? It turns out a lot. First, reduce the leakiness of the BBB8. Leakiness is usually caused by increased production of leukotrienes derived from arachidonic acid (AA). The best way to reduce arachidonic acid is to follow a strict Zone Diet.

Second, increase the levels of omega-3 fatty acids in your blood so more omega-3s can get into the brain to generate resolvins. If you happen to have the ApoE4 mutation, then you should take even more omega-3 fatty acids which include EPA and DHA from fish oil9.

Not surprisingly, the AA/EPA ratio is higher in Alzheimer’s patients than in age-matched normal subjects10. Zone Labs offers a Cellular Inflammation Test Kit that you can use to find your AA/EPA ratio. If you want to be even more preventative, then add high-doses of polyphenols to your diet, as they demonstrate an increase in cognitive improvement, most likely by reducing insulin resistance in the brain11.

The best prevention for inflammation in the brain is a comprehensive anti-inflammatory nutrition program which includes calorie-restriction, without hunger or fatigue, coupled with high-doses of omega-3 fatty acids and polyphenols. The diet has to be adequate in protein, moderate in carbohydrate (but rich in fermentable fiber), and low in fat (especially omega-6 and saturated fats) which is built into the Zone’s program.

If people don’t start following an anti-inflammatory diet, Alzheimer’s rates will continue to rise and tax dollars will continue to skyrocket, funding research in the wrong area of focus — preventing the formation of amyloid plaques.

Research has proven that amyloid plaques can actually be useful. In animal models, researchers were able to prevent the formation of amyloid plaques through genetic engineering, but the animals quickly died of infection when microbes entered their brains4. It is the resolution of inflammation left by amyloid plaques, and not the plaques themselves, that is the real danger in terms of Alzheimer’s.New call-to-action


  1. Bennett DA et al. “Neuropathology of older persons without cognitive impairment from two community-related studies.” Neurol 66:1837 (2006).
  2. Morris JC et al. “ApoE predicts amyloid-beta, but not tau Alzheimer pathology in cognitively normal aging.” Ann Neurol 67:122 (2010).
  3. Herrup K. “The case for rejecting the amyloid cascade hypothesis.” Nat Neurol 18:794 (2016).
  4. Kumar DKV et al. “Amyloid-beta peptide protects against microbial infection in the mouse and worm models of Alzheimer’s disease.” Science Translational Medicine 8:340ra72 (2016).
  5. Backes WH et al. “Blood-brain-barrier leakage in patients with early Alzheimer’s disease.” Radiology doi.org/10.1148/radiol.2016152244 (2016).
  6. Wang W et al. “Resolution of inflammation is altered in Alzheimer’s disease.” Alzheimer’s and Dementia 11:40 (2015).
  7. Vandal M et al. “Reduction in DHA transport to the brain of mice expressing human APOE4 compared to APOE2.” J Neurochem 129:516 (2014).
  8. Cloughesy TF and Black KL. “Pharmacological blood-brain-barrier modification for selective drug delivery.” J Neuro-Oncology 26:125 (1995).
  9. Chouinard-Watkins R et al. “A diet rich in docosahexaenoic acid restores liver arachidonic acid and docosahexaenoic acid concentrations in mice homozygous for the human apolipoprotein E ϵ4 allele.” J Nutr doi:10.3945/jn.116.230052 (2016).
  1. Conquer JA et al. “Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment.” Lipids 35:1305 (2000).
  2. Bell L et al. “A Review of the Cognitive Effects Observed in Humans Following Acute Supplementation with Flavonoids, and Their Associated Mechanisms of Action.” Nutrients 7:10290 (2015).

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