Kerry D Friesen, M.D.

Inflammation Overload!

Posted on 25. Jan, 2009 by Kerry D Friesen, M.D. in Brain Health, Men's Health, Women's Health

Remember you heard it here first.

There now exists a formidable body of literature linking cardiovascular disease and neurodegenerative disorders. More than ten years ago I found myself lecturing my patients on the not-so- subtle connection between abdominal obesity; insulin resistance; syndrome-X and endothelial-cell dysfunction. With abdominal obesity, fat is progressively packed around internal organs until it literally takes on a life of it’s own. Adipocyte (fat cell) signalling becomes so strong that it becomes the dominant “endocrine” or hormone secreting organ in the body. In the vernacular, all hormonal “hell” breaks loose.

IT’S ALL ABOUT BALANCE

Resistance is futile. You have become one with your fat cells. The delicate yin and yang balance between your immune system and other major organ systems is lost. The cytotoxic and neurotoxic effects of inflammatory mediators like TNF-alpha; peroxynitrite and IL-6 to name a few, reign supreme. Over time, free-radical formation and the subsequent oxidative damage result in irreversible mitochondrial DNA decay and cell death. If the affected cells reside in your brain, then any one of a multitude of neurodegenerative diseases is possible. If they happen to line the vascular endothelium in your heart, then you are well on you way to your first heart attack.

Most people reading this blog will find themselves in between the two extremes. In this “no-mans land” of disease, doctors euphemistlcally tell patients they have a “touch of sugar” (you have frank diabetes) or their blood pressure is a “little elevated” (you’ve been diagnosed with high blood pressure) or your “good cholesterol” (HDL) is a little low (you are at high-risk for heart disease and diabetes). I could go on…

INTERLEUKIN-6 FYI: FOR YOUR INFLAMMATION

As it turns out, the common denominator in the above scenario is inflammation overload. Nothing, not even the micro-circulation of the brain escapes the damaging effects of IL-6 and tumor-necrosis factor-alpha. Atherosclerosis “hardening of the arteries”, impairs blood flow to the already hypermetabolic brain tissue, as a result underperfused neurons respond with ß-amyloid plaque deposition, acetylcholine signaling defects, oxidative stress and more inflammation.

The only known genetic risk factor for Alzheimer’s disease not surprisingly, is a gene that codes for Apolipoprotein E4. Apolipoprotein E in one of its three isoforms, is responsible for the transport of triglyceride, phospholipid, cholesteryl esters, and cholesterol into cells.

Of the three main isoforms of the apo E allele, apoE3 is most common, followed by apoE4 and lastly apoE2. The lifetime risk for Alzheimer’s disease in someone with apoE3 is about 9%. The lifetime risk for Alzheimer’s in someone with the apoE4 allele is a whopping 29%. If you happen to be homozygous for apoE4 (both alleles on paired chromosomes are apoE4) the lifetime risk for Alzheimer’s sky-rockets to 91% by age 80. Apparently the apoE4 allele is so inefficient at cholesterol metabolism within the brain that sulphated galactocerebroside (sulphatide) levels drop. Sulfatide has everything to do with neuronal plasticity, cell growth and repair in addition to normal signal transduction.

How do you know if you possess the apoE4 allele? While various labs offer this test Berkley Heart Lab is consistently the most reliable.

In addition, the one-time Apo E test will help decide whether or not diet will have an effect on elevated cholesterol levels. If you possess the apoE4 isoform without question diet therapy can have dramatic effect on your LDL-C (bad cholesterol) levels. If you have seen your doctor and were told you had elevated LDL-C and have altered your diet without success, then this test is for you.

Here are the five easy steps I recommend for my patients. In this case, I personally take a double dose of my own medicine.

1. Consider Apolipoprotein E testing (ask your doctor)
2. Adopt the Mediterranean diet
3. Increase Omega-3-FA consumption
4. Decrease Omega-6-FA intake (PUFA in the form of vegetable oil)
5. Dramatically increase your intake of dietary polyphenols† (see list below)

PASS THE POLYPHENOLS PLEASE

To put it another way, make a concerted effort to bathe your body’s biochemical milieu daily in a rich blend of phytochemicals. This is the essence of the “French Paradox”, that is, while the French consume much more saturated fat than their North American counterparts, they also consume far less omega-6-FA’s and far more polyphenols (in the form of red wine primarily), and have much less heart disease to show for it. It is precisely when science flies in the face of convention that you know you’re “gettin’ warm”.

†Food sources rich in polyphenols include onion, apple, green-tea, red wine, red grapes, grape juice, strawberries, raspberries, blueberries, cranberries and walnuts to name a few.

Polyphenols can be classified as non-flavonoids and flavonoids. The flavonoids quercetin and catechins are currently the most extensively studied polyphenols.

Tags: apo E, coronary artery disease, endothelial cell dysfunction, IL-6, inflammation, polyphenols