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Beyond Cholesterol: The Real Link Between Diet and Heart Disease

One of the best ways to live longer is to reduce your likelihood of dying from a heart attack since it continues to be the #1 killer in America. If we could prevent heart disease tomorrow, it is estimated that the average life expectancy of every American would increase by ten years.

We are led to believe by extensive drug marketing that elevated cholesterol is the cause of heart disease.  Unfortunately, about 50 percent of the people who are hospitalized with heart attacks have normal cholesterol levels. What’s more, 25 percent of people who develop premature heart attacks have no traditional cardiovascular risk factors at all.  So what if cholesterol was only a minor, secondary player in developing heart disease?

 The Cholesterol Hype

Cholesterol does have a role in heart disease, but it is a secondary factor that plays a far lesser role in fatal heart attacks than the marketing of drug companies leads you to believe.

It has been known since 2001 that oxidized LDL is a far better predictor for the development of atherosclerotic lesions than the traditional measurement of LDL (1). But it was also at this time that the first statin studies began to appear. This gave the pharmaceutical industry a patented drug to “prevent” heart disease but unfortunately statins could not specifically lower oxidized LDL.  Furthermore, the LDL story was such an easy story to tell because it could be summarized “if your cholesterol levels are high, you are going to die”.  That marketing statement ignored the fact that the most common drug (i.e. aspirin) to prevent heart attacks had no effect on reducing cholesterol. Today lowering LDL cholesterol (but not necessarily lowering oxidized LDL) is the number-one priority of every cardiologist in America.

Various epidemiological studies have found that increased serum cholesterol levels occur more often in heart disease patients. But that increase is only 5 to 10 percent higher in those who develop heart disease than those who don’t. This doesn’t help explain why about half the people who die from heart disease don’t have elevated LDL cholesterol levels (less than 130 mg/dl). It also means that high LDL cholesterol is not a very good predictor of heart disease. On the other hand, a very different picture emerges if you look at the levels of oxidized LDL levels. You can see a very striking relationship in the prediction of heart disease with increasing levels of oxidized LDL levels (1).  Even so the best way to lower oxidized LDL is not a statin, but high-dose polyphenol extracts (2), since they have anti-oxidant properties to help combat oxidation.

 Unresolved Cellular Inflammation: The Reason Heart Disease Kills

A heart attack is simply the death of the muscle cells in the heart due to lack of oxygen caused by a constriction in blood flow. If this lack of oxygen is prolonged, and enough heart muscle cells die, your heart attack becomes a fatal one. What causes that constriction in blood flow is the rupture of soft vulnerable plaques that line the artery.  Although you can’t see them, when they rupture they release a mass of cellular debris that accelerates the clotting process to stop blood flow and therefore stop oxygen from being delivered to the heart.

The reason heart disease remains the primary killer of Americans is not due to cholesterol, but unresolved chronic inflammation in the arteries that causes these soft vulnerable plaques to rupture.  You may be asking yourself, “What on earth is unresolved cellular inflammation?” This is simply inflammation that falls below the threshold of perceived pain. That’s what makes it so dangerous. You have no indication it is present and therefore you make no effort to reduce it.  This inflammation results from an increased production of inflammatory mediators such as eicosanoids. Statins have no effect on reducing eicosanoid levels in the body.

Eicosanoids, Resolvins, and Heart Disease

Eicosanoids are the hormones that intensify inflammation.  You need some to activate the immune system, but in excess they promote cellular inflammation.  These hormones are generated by the combination of high levels of insulin and omega-6 fatty acids in your blood.  On the other hand, resolvins are the hormones that resolve inflammation. These hormones are generated by the levels of omega-3 fatty acids in your blood. You need to have both eicosanoids and resolvins in the proper balance in order to be in a state of wellness because you have to turn on inflammation as well as turn it off. Unfortunately, most of us produce too many eicosanoids, which leads to increasing levels of unresolved cellular inflammation and eventually to chronic diseases like heart disease.

Managing Unresolved Cellular Inflammation

The Zone Diet was developed primarily to reduce the overproduction of eicosanoids. Adequate levels of omega-3 fatty acids in the diet (usually requiring supplementation) will ensure adequate levels to promote the formation of resolvins.

A variety of factors forge the linkage between unresolved cellular inflammation and fatal heart attacks. First of all, eicosanoids make soft vulnerable plaque more likely to rupture. Eicosanoids act as powerful constrictors of your arteries and can lead to a vasospasm, a potentially fatal cramp or “charley horse” that prevents blood flow to the heart. Vasospasm is the second cause of fatal heart attacks. In addition, lack of sufficient levels of omega-3 fatty acids in the heart muscle can also lead to a fatal heart attack caused by chaotic electric rhythms in the heart. This condition, called sudden death, accounts for more than 50 percent of all fatal heart attacks.

How can you tell if you have the right balance of eicosanoids to resolvins for heart health?  That knowledge comes from the AA/EPA ratio in the blood.  Arachidonic acid (AA) is the building block of eicosanoids and eicosapentaenoic acid (EPA) is the building block of resolvins.  You want to maintain that AA/EPA ratio close to 1.5, and ideally have about 4 percent of your total fatty acids in the blood consisting of EPA (3-5)

How The Zone Can Help Promote A Healthy Heart

For optimal heart health you need the appropriate balance of eicosanoids to resolvins. This is why I recommend a multi-factorial dietary approach. This entails the Zone Diet, omega-3 fatty acids, and polyphenol extracts. The Zone Diet can help reduce the overproduction of eicosanoids. Consuming adequate levels of omega-3 fatty acids can help increase the production of resolvins and the use of maqui polyphenol extracts can help minimize oxidized LDL (2).  This three-part dietary system or what I call the Zone Pro-Resolution Nutrition system will all be described in greater detail in my upcoming book, The Resolution Zone.{{cta('14dee37e-1816-403a-a6e8-a67c8b9cf45b')}} References

  1. Holvoet P, Mertens A, Verhamme P, Bogaerts K, Beyens G, Verhaeghe R, Collen D, Muls E, and Van de Werf F. “Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease.”  Arterioscler Thromb Vasc Biol 21:844-848 (2001)
  2. Davinelli S, Bertoglio JC, Zarrelli A, Pina R, and Scapagnini G. “A Randomized Clinical Trial Evaluating the Efficacy of an Anthocyanin-Maqui Berry Extract on Oxidative Stress Biomarkers.”  J Am Coll Nutr 34 Suppl 1:28-33 (2015)
  3. Sears B. “Omega-3 fatty acids and cardiovascular disease:  Do placebo doses give placebo results?”  CellR4 5:e2302 (2017)
  4.  Sears B. “Omega-3 fatty acids and cardiovascular disease: Dose and AA/EPA ratio determine the therapeutic outcome.”  CellR4 6:e2531 (2018)
  5. Sears B. “Appropriate doses of omega-3 fatty acids for therapeutic results.” CellR4 6: e2578 (2018) 

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Dr. Sears Q&A: Weight Loss

With so much interest in weight loss and so much buzz around weight loss drugs, we put together some of the top questions we get in this latest Q&A blog. Here Dr. Sears answers your questions on weight loss, weight loss drugs and what he thinks is the most scientifically backed way to lose weight. See what he has to say.Question: What medical conditions could impede weight loss, and how can they be identified?  Answer:  Any condition associated with insulin resistance will make it difficult to lose weight.  This would include diabetes, heart disease, neurological disease, etc.  Also, any drug that induces insulin resistance will also make it difficult to lose weight.  These include corticosteroids and many neurological drugs. Question: How do hormones affect weight loss, and which imbalances are most detrimental? Answer: High levels of insulin (caused by insulin resistance), high levels of cortisol (caused by stress), and low levels of satiety hormones such as GLP-1 will make weight loss difficult. Question: Is there a connection between sleep quality and weight loss? Answer: Poor quality sleep increases cortisol levels that lead to insulin resistance. The higher your level of insulin resistance, the more difficult it is for any organ to remove glucose from the blood for transport into the cell, where it can be converted to energy. This i Question: Do any weight loss supplements work?  Answer: Not really. You have to restrict calories to activate AMPK which causes your body to effectively burn excess stored body fat.   Question: What medications are FDA approved for weight loss? Answer: There are number of approved older drugs, but the most widely used is still an old drug (Phentermine) that was only recently approved for long-term use. However, the new injectable GLP-1 receptor agonists are more powerful and more popular. The scientific name for the most well-known injectable weight-loss drug is semaglutide, which is marketed under the tradenames Ozempic and Wegovy. In simple terms, these injectable drugs activate the release of the hormone GLP-1 from the gut that goes directly to the brain to tell you to stop eating. These drugs were initially developed to treat type 2 diabetes, but the clinical studies in overweight and obese individuals demonstrated significant weight loss at higher levels. Question: What are the unintended side effects of weight loss medications (i.e. GLP-1s, dual GIP/GLP-1). Answer: One major problem is that the lack of hunger caused by the drug makes you less likely to consume sufficient protein to maintain lean body mass.  Lean body mass is defined as functional tissue such as organs (including the brain) and bone.  Nearly 40 percent of the weight loss in obese patients comes from loss of lean body mass.  Without adequate protein (especially on a diet that is calorie-restricted because of lack of hunger), the replacement of damaged cells is compromised.  The skin and hair are the first site to suffer.  This lack of protein also makes it difficult to maintain mitochondrial function that provides energy for each of your 30 trillion cells. As a result, fatigue (both mental and physical) is often experienced. Question: Would you recommend an injectable weight loss drug? Answer: The answer is no. There is a big difference between weight loss and fat loss. Weight loss is the combined loss of stored body fat and lean body mass (i.e., muscle). You want to lose fat but not muscle. Although the weight loss using weekly semaglutide injections is impressive according to the literature, a deeper look shows that about 40 percent of that weight loss is due to loss of lean body mass. That is not a good sign. It suggests that the injections reduce hunger to the extent that the person has little desire to eat enough protein to maintain muscle mass. In essence, the drug increases the patients' sarcopenia (muscle loss). One of the consequences of sarcopenia is increased frailty. Also once you stop using these weight loss drugs, the weight quickly returns. Question: Does a high protein diet help with weight loss? Answer: Most high protein diets are ketogenic diets that disrupt metabolism in addition to being high fat.  The appropriate diet is protein-adequate (about 30 grams of protein at each meal), carbohydrate-moderate (primarily non-starchy vegetables, low-fat (to reduce calories) and rich in fermentable fiber.  The common name for such a diet is the Zone diet. The ideal amount of protein at each meal for weight loss is about 30 grams. Less than 30 grams of protein at meal will not generate the hormonal signals from the gut to stop hunger. Too much protein at meal, greater than 30 grams, will inhibit AMPK activity which helps cells burn excess stored fat.  

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Aging: Can You Slow It Down?

The first few weeks of the New Year are often focused on the resolve to lose weight, when in actuality people should focus their goals on slowing down aging, no matter the time of year. The only regimen that clinically achieves results in slowing the aging process is calorie restriction without malnutrition. Why? It’s not simply losing weight but orchestrating the complex interplay of reducing senescent cells, reprograming your metabolism, and changing gene expression, leading to a longer and better life.   A Timeline of Calorie Restriction   The first recorded human experiments with calorie restriction began with the written books of Luigi Cornaro in the 16th century, as I outlined in my book The Anti-Aging Zone, published in 1999. However, the molecular mechanisms of why calorie restriction is so effective required more recent breakthroughs in metabolism and epigenetics that were confirmed with the CALERIE study that carefully controlled the diets of 225 participants over two years and then ongoing testing of their retained blood samples.     The results of the CALERIE study have been impressive. However, the one clear take-home lesson was that reduction of insulin resistance was the most predictive blood marker correlated with the genetic changes and the decrease in senescent cells that ultimately accelerate aging.   The Zone on Calorie Restriction   The Zone diet is a calorie-restricted diet that was patented to reduce insulin resistance. It requires balancing macronutrients at each meal to generate the rapid hormonal changes that give rise to satiety. Only then can you follow calorie restriction for a lifetime without hunger and fatigue. It starts with having enough protein at each meal to create satiety in the brain's appetite control center. You need about 30 grams of protein (no more, but no less) at each meal to generate the same hormonal responses induced by the recent injectable weight loss drugs. However, you also must balance that protein with an adequate level of low-glycemic carbohydrates (about 40 grams) to stabilize blood glucose levels, and then add a dash of monounsaturated fat (about 15 grams). Over the years, it has been demonstrated by more than 40 research publications that the Zone diet is superior to ketogenic diets and the Mediterranean diet under controlled clinical research.    A New Technology to Slow Down Aging  Unfortunately, many people think the Zone diet requires too much thinking.  That’s why I developed Zone Foods to overcome that problem. The first generation of Zone Foods demonstrated dramatic reductions in insulin resistance compared to a control group, getting an equal number of calories (1). The second generation of Zone Foods offers greater variety and even more appetite suppression without thinking. This second generation will include new and improved versions of the Zone Pasta and Zone Bars, with new additions of Zone Muffins, Zone Oatmeal, Zone Granola, Zone Soups, and Zone Cookies (coming soon!). Each Zone Food contains 15 grams of protein, balanced with the appropriate level of low-glycemic carbohydrates, so any combination of two Zone Foods will provide the critical 30 grams of protein at a meal to stop hunger and maintain peak mental awareness for the next five hours. The growing variety of Zone Foods makes following the Zone diet incredibly easy. If you are never hungry, that indicates that you are reducing insulin resistance. The long-term benefit to you is slowing aging, which is only possible with lifelong use of Metabolic Engineering that starts with the Zone diet as its foundation. You May Also Like: Reaching the Zone Using Metabolic Engineering

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