INFLAMMATION PART 6 ENDOTHELIAL DYSFUNCTION
DIFFERENT TYPES OF LDL.
From the above discussion I mentioned the different types and patterns of LDL. Let’s examine them a little closer. Basically we have two main types of LDL particle (in addition to a recently discovered very atherogenic, glycated particle). If you get a special blood test called a lipoprotein profile using NMR technology such as the one offered by LipoScience® your blood will have a predominance of either pattern type A or pattern B lipoproteins. Pattern A which contains the large, fluffy, and buoyant particle type is harmless because it does not oxidize easily. It’s the healthy, preferred form to have. Then there is pattern B where the sdLDL particle predominates. Pattern B is highly atherogenic. It is associated with three times more likely chance to cause a heart attack than pattern A. It is small, easily oxidized, and easily slips under the endothelium. Pattern B is the one associated with metabolic syndrome which is a highly inflammatory, prediabetic, atherogenic disorder affecting 80 million Americans.
It is interesting that most of the discussion in your doctor’s office, refers to LDL as if there were only one type. Yet only one type promotes disease i.e., the small, dense, easily oxidized type found in pattern B. That’s why having your cholesterol checked from the device in doctor’s office is incomplete. That test gives only a gross accounting of total LDL and not the type of LDL which predominates in you.
THE AHA RECOMMENDED DIET PROMOTES PATTERN B
The next obvious question is how does one develop pattern B? Scientists speculate that pattern B LDL is easier to oxidize because it is small and dense. The easiest way to develop pattern B is to eat Elite. That means eat according to the AHA and the USDA’s recommendations. I know it sounds strange that the AHA would recommend a diet that promotes heart disease but that’s exactly what they are doing. Is this deliberate, accidental or just bad advice? I don’t really know. I’ll give them a break and say no, it’s not deliberate but it’s still baffling. The Elite’s recommendations are antiquated, and completely outdated yet these same people cannot muster up the courage to admit that they were wrong. To save face they simply ignore the results of hundreds of studies that contradict their penchant toward a high-carb, high omega 6 PUFA diet. That’s all fine and dandy if you are interested in staying sick. While they save their faces we sacrifice our hearts and much more. Politics as usual I guess.
AVOID THE HEART SMART POLYUNSATURATED OILS
Do what I did and ignore their dangerous advice. Rather than politics as usual you will not want to eat Elite. Here’s one good reason. The endothelial surface contains special enzymes that can readily oxidize LDL. The longer LDL is exposed to these surface enzymes the better chance of being oxidized. The membrane of the LDL particle is particularly susceptible to oxidation if it is formed from Ω6PUFA and far less susceptible to oxidative damage if made of saturated fat. The findings of a Harvard study show that a diet rich in omega 6PUFA leads to a worsening of cardiac health while diets rich in saturated fat healed their atherosclerosis.
A 2004 study from Brigham and Women’s Hospital and Harvard School of Public Health showed that in postmenopausal women, the more PUFA [Ω6PUFA] they ate, and to a much lesser extent the more carbohydrate they ate, the worse their atherosclerosis became over time. The more saturated fat they ate, the less their atherosclerosis progressed; in the highest intake of saturated fat, the atherosclerosis reversed over time.[1]
When it leaves the liver LDL is in the form of VLDL (very low density lipoprotein see Fig. 9) which is rich in triglycerides (TG). After dropping off some TG to muscle cells, fat cells, and other tissues in need, it eventually becomes LDL (low density lipoprotein). However, once the lipoprotein leaves the liver it is vulnerable to oxidation no matter what form it’s in. Therefore, as VLDL travels around and eventually becomes an LDL particle some oxidation may have occurred. The longer it remains in the blood stream exposed to endothelium the greater chance it has of becoming more oxidized. As Dr Russell Blaylock puts it:
When inflammation occurs in the body, for whatever reason, immune cells release inflammatory chemicals called cytokines and chemokines. If this state of inflammation persists too long, LDL cholesterol begins to oxidize (take on an extra electron). LDL cholesterol is singled out because it is a smaller molecule and more likely to oxidize than larger molecules such as high-density lipoprotein (HDL) cholesterol. (However, under certain conditions HDL cholesterol can oxidize and contribute to atherosclerosis.)
MY SUPER MEDITERRANEAN DIET PROMOTES PATTERN A
Once the body’s antioxidants are all used up LDL becomes oxLDL, and often times winds up in a foam cell. We also know that the greater the quantity of oxLDL in a person’s blood the greater the associated risk for heart disease (see above graphs). This is a much more reliable risk factor to examine in a patient than a simple LDL cholesterol assay. Because of the propensity to oxidize we do not want to have pattern B with sdLDL particles floating about just waiting to drop kick you into a shallow grave. You want to be in an antiinflammatory state where LDL cannot easily convert into oxLDL. To accomplish this we want to be sure to:
- Do what’s needed to convert your LDL pattern from B to A. There are several things we can do. The main one is a dietary change. Numerous studies clearly show that by reducing non-fibrous carbohydrate consumption you lower triglycerides (TG), raise your HDL and effortlessly convert your LDL into the harmless pattern A. My SMD plan does this very effectively. It’s a moderate (safe) carb, moderate protein, higher (safe) fat diet. Trial after trial demonstrates the enormous changes in lipid status (changes into pattern A) and the massive decrease in oxidative stress when employing this special type of diet. Part of the SMD’s success is from using therapeutic doses of fish oil. Adding fish oil further amplifies the beneficial effect on both lipids and inflammation by both decreasing TG’s and changing LDL to pattern A.
- Do what you can to change your oxidation status and reduce excessive free radical formation in your body. For example, in the Everything Gives You Cancer chapter I recommend blenderized FAV’s with raw, organic, cacao powder. Raw, or for that matter processed cacao, is an amazingly powerful antioxidant which has been shown to markedly lower oxLDL levels with daily consumption. There are several other antioxidants that I discuss in this book. All are useful for this purpose as is the generous consumption of FAV.
- Do not eat proinflammatory foods. Another major player is avoiding Ω6PUFA which puts your LDL at much greater risk for oxidation. My SMD eliminates all Industrial Dinners and other sources of Ω6PUFA. Instead we eat more Ω3PUFA, monosaturates like EVOO, and saturated fats like coconut oil. Excessive sugar consumption is also proinflammatory. My SMD reduces the consumption of simple sugars and replaces them with fresh FAV.
- Get plenty of exercise. Moderate daily exercise is anti-inflammatory. It acts as a powerful tool for reversing much of the damage a poor lifestyle dishes out. Marathon runners, especially by their fourth decade and older, and those that push themselves too hard are generating inflammation-do not abuse yourself. Moderate exercise, even sprinting intervals, is healthy but going ape is not smart.
Chronic sugar and excessive non-fibrous carbohydrate (like bread for example) consumption increases your TG, lowers HDL and promotes pattern B. Keep in mind that anything rapidly converted to sugar like cereal grains works just as well as pure sugar in raising your TG, lowering HDL and promoting pattern B. Fructose is particularly bad as it can raise TG’s very rapidly.
Figure 9 Lipoprotein degradation after excretion from the liver[2]
Furthermore, the same antioxidant strategy we use for preventing the formation of oxLDL works to eliminate endothelial dysfunction as well. In fact, you will see that my Super Mediterranean Diet (SMD), and my food pyramid provide an antioxidant rich environment for the prevention of many disorders caused by a modern lifestyle including pattern B. Therefore, always strive to eat an antioxidant rich diet full of fresh fruits and veggies (FAV). Don’t stress over your cholesterol level per se, stress over your “oxidative stress.”
Whether LDL can initiate damage to the endothelium by itself is academic because my anti-inflammatory regimen heals endothelium and reduces oxLDL at the same time. Even if regular old LDL (pattern A) could, through some miracle of junk science, become implicated in causing heart disease on its own it still needs to be oxidized at some point before it can generate an immune response. However, it appears that in spite of millions of dollars spent on research to prove elevated LDL to be an important initiator of disease no such connection has ever been confirmed. The above graphs by Barry Sears show oxLDL clearly increases CVD risk not LDL, which is consistent with everything we talk about in this book. Therefore, the idiot rule for addressing this entire enterprise is to simply follow my suggestions which will reduce oxidation, and inflammation regardless of which biochemical pathway science eventually proves to be responsible for the atherosclerotic pathway.
ALL BETS ARE OFF
Many authors would have you believe that LDL cholesterol plays no role in atherogenesis. I’m one of them. While native LDL may indeed be harmless all bets are off regarding your LDL if you are in an inflammatory state and consume significant amounts of omega 6PUFA. To quote Dr Blaylock:
The only real reason high levels of LDL cholesterol are dangerous is that the more you have, the more likely it is that some of it will oxidize and many of the fats we eat, especially omega-6 fats (vegetable oils) are actually oxidized on our plates, even before we eat them.”
We do have proof that diets rich in “heart smart” oils promote LDL oxidation and progression of atherosclerosis (A 2004 study from Brigham and Women’s Hospital and Harvard School of Public Health see above) and diets rich in saturated fat & cholesterol decrease LDL oxidation. [Emphasis mine]
SIMPLE REALLY
By eating according to my plan and following my lifestyle suggestions both culprits, endothelial dysfunction and oxLDL are dealt with in short order. It’s a one size fits all approach and it works exceedingly well. That’s also what makes it so simple. You do not have to anguish over each risk factor and how best to quell their harmful effects using dozens of supplements, pills and powders. This is also the main reason why you must consume only pharmaceutical grade fish oil that is not oxidized i.e., rancid, since any rancid oil is highly atherogenic. Furthermore, be sure to take your antioxidant vitamins like vitamin E with your fish oil to eliminate the chances for it to oxidize once in your body.
In summary the very beginnings of atherosclerosis require two players: injury to the endothelial surface-endothelial dysfunction-and oxLDL. OxLDL can first form in the bloodstream, and can therefore initiate endothelial damage on its own. Likewise, endothelial dysfunction opens another wide pathway for sdLDL to become trapped and oxidized. Therefore one of the best preventive things you can do is start eating according to my SMD plan which encompasses the above suggestions 1 through 4. This approach has a healing effect on the endothelium, it reduces oxLDL, and atherosclerosis. But wait there’s more: a multitude of other, related, inflammatory diseases such as cancer, stroke and hypertension are dealt with as well. Read the dietary advice chapter, Welcome to the Industrial Diner, for a more thorough explanation on safe fats and safe carbohydrates.
NITRIC OXIDE AND ENDOTHELIAL DYSFUNCTION: THE FIRST AMIGO OF INFLAMMATION
OxLDL is concerning because it can activate or damage the endothelium on its own. We will now cover other irritating agents (IA) that can cause endothelial dysfunction which is at the very core of this disease.
Every single person with atherosclerosis has endothelial dysfunction. It is the uniting concept through which coronary artery disease must be understood.
Current research supports the theory that the endothelium, the living, breathing, endocrine organ, is at the core of the initiation of disease while oxidized LDL (which may also be the initiator of disease) promotes and keeps the process active along with a host of other factors. We call this endothelial dysfunction or more specifically endothelial “activation” as the initial step. If we are to prevent heart disease from forming or progressing we must understand what causes endothelial activation and what we can do to stop the process or even to reverse it. So what exactly is the endothelium?
The endothelium is a very active, living organ of approximately 2 tennis courts in surface area if laid out end to end-which line every blood vessel in the body.
The endothelial cell (EC) produces antiplatelet and antithrombotic [blood clot] components to keep the lumen open. It also produces vasodilators and vasoconstrictors to regulate blood flow. ECs line vessels in every organ system and regulate the flow of nutrient substances, diverse biologically active molecules, and the blood cells themselves. This gate-keeping role of endothelium is effected through the presence of membrane-bound receptors for numerous molecules including proteins (e.g., growth factors, coagulant, and anticoagulant proteins), lipid transporting particle (e.g., low-density lipoprotein [LDL]), metabolites (e.g., nitrous oxide and serotonin), and hormones (e.g., endothelin-1), as well as through specific junctional proteins and receptors that govern cell-cell and cell-matrix interactions.[3]
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Figure 10 Endothelial balance: vasodilatation Vs vasoconstriction[4]
[The] endothelium produces vasodilators and vasoconstrictors, procoagulants and anticoagulants, inflammatory and anti-inflammatory, fibrinolytics and antifibrinolytics, oxidizing and antioxidizing, and many others [Figure 10]. When endothelial cells lose their ability to maintain this delicate balance, the conditions are right for the endothelium to be invaded by lipids and leukocytes (monocites (sic) and T-lymphocytes). The inflammatory response is incited and fatty streaks appear, the first step in the formation of the atheromatous plaque. If the situations persist, fatty streaks progress and the plaque are exposed to rupture and set the condition for thrombogenesis and… vascular occlusion [heart attack]. [5]
[1] (http://www.cholesterol-and-health.com/Does-Cholesterol-Cause-Heart-Disease-Myth.html) 12/14/2011
[2] The Brain, the liver, and diabetes; http://www.biochem.arizona.edu/classes/bioc462/462bh2008/462bhonorsprojects/462bhonors2007/gsantarelli/lipidhomeostasis.html (From original [Nelson and Cox , page 822, 2004]) 12/16/2011
[3] Blood. May 15, 1998 vol. 91 no.
[4] Regulatory functions of the endothelium. Normal or anti-atherogenic vs dysfunction or atherogenic propierties. From Esper RJ, et al.[5] Esper et al. Cardiovascular Diabetology 2006 5:4 doi:10.1186/1475-2840-5-4
[5] Ricardo J Esper, Endothelial dysfunction: a comprehensive appraisal http://www.cardiab.com/content/5/1/4
Category: ENDOTHELIAL DYSFUNCTION, Inflammation, PREVENTIVE MEDICINE
