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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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062524---Keto-Blog

Ketogenic Diets and Aging

Chances are, you or someone you know has tried the keto diet at some point in time. This high-fat, very low-carbohydrate eating plan appeals to many due to its promise of rapid weight loss. In this blog, Dr. Sears explores some of the latest scientific findings on ketogenic diets and provides caution before hopping on this trend. What is a Ketogenic Diet? The ketogenic diet is a high-fat, very low-carbohydrate eating plan. This significant reduction in carbohydrates to induce a metabolic state is called ketosis. This only occurs when there is not enough carbohydrates in your liver to completely convert fatty acids to carbon dioxide and water. The normal conversion generates the chemical energy (ATP) that keeps us alive. In the absence of ketosis, each fatty acid generates 108 molecules of ATP when oxidized in the mitochondria. Ketone bodies make less ATP when they are metabolized by mitochondria. How much less? About five times less. This is like switching the gasoline in your car from high-octane fuel to low octane fuel as ketone bodies increase in the blood. Furthermore, contrary to popular belief, ketones are not an ideal energy source for the brain, as glucose remains the preferred fuel for ATP production in brain cells. Lack of blood glucose is a highly stressful situation for the brain. This is why the body secretes the stress hormone cortisol from the adrenal glands during ketosis to breakdown protein and convert the amino acids into glucose for the brain. This explains why even under complete starvation for 38 days, the blood glucose levels never dropped below 68 mg/dL. This is still considered as a normal blood sugar level. Where did this blood glucose come from if there was none in the diet for 38 days? The answer is neo-glucogenesis primarily using lean body mass. Ketogenic Diets Pros and Cons Interest in ketogenic diets rises and falls about every 20 years. They’re very low-carbohydrate diets that claim that carbohydrates make you fat and keep you fat. This is simply not true. It is not carbohydrates per se but a disrupted metabolism that makes you fat. To be more specific, it is the inhibition of AMPK, the master regulator of your metabolism that makes you fat. Why? As AMPK activity increases, you burn stored fat faster. Frankly, I’ve always been amazed by the re-emergence of ketogenic diets. Eighteen years ago, I published the premier clinical study demonstrating that, under equal calorie intake in which all the food was provided to the subjects for six weeks, the Zone Diet was better than a ketogenic diet in reducing total weight, excess body fat, and inflammation. Now, a recent study revealed some more very concerning findings about the long-term effects of ketogenic diets. This new study indicated that following a keto diet causes a rise in senescent cells, popularly known as “zombie cells.” Zombie Cells are damaged cells that no longer divide but don't die. That’s bad enough, but zombie cells continue spreading inflammation throughout the body. As the number of zombie cells increases in your body, they become a living nightmare. Why? Zombie cells accelerate aging because they cause the earlier development of many chronic diseases. In this study they found that zombie cells in the animals began to appear while they were on a ketogenic diet. The zombie cells then disappeared when researchers changed the diet to a “non-ketogenic diet” (i.e., the Zone diet). And when the animals were given a Keto diet again, the zombie cells reappeared. Notice a trend? If you want to hear more about this study you can listen to our recent podcast at Dr.Sears.com. Based on earlier blogs, this adds to the list of downsides for following a ketogenic diet versus the Zone Diet. PROS Rapid initial weight loss: This is primarily due to the loss of retained water from the glycogen stores in the liver, which is rapidly used up to maintain blood sugar levels. Since these glycogen stores in the liver contain significant levels of retained water, much of the initial weight loss is water rather than stored body fat. If your main goal is loss retained water, this can be seen as a benefit. Of course, going to a sauna would also work. Reduced hunger: Ketogenic diets are rich in protein. Any increase in protein intake can help reduce hunger. CONS Production of acetone: One of the ketone bodies produced during ketosis is acetone, which is also the main chemical in nail polish. Increased calcium loss: A ketogenic diet can lead to higher calcium loss from bones. Limited fat utilization: High levels of dietary fat reduce the likelihood of using stored body fat for energy unless you also significantly restrict calories. Reduced energy levels: The lack of ATP production on a ketogenic diet can lead to easier fatigue during mild exercise. Damage from cheat meals: After seven days on a keto diet, a single high-carb cheat meal can damage blood vessels. Lack of polyphenols: This makes it difficult to activate genes that optimize metabolism by improving mitochondrial efficiency in converting fat into ATP. No long-term weight loss advantage: Long-term studies show no difference in weight loss between a ketogenic diet and a low-fat, high-carb diet. No short-term metabolic advantage: Careful studies demonstrate that fat loss on a ketogenic diet is the same as on a low-fat, high-carb diet with the same caloric intake. Compromised gut health: A lack of fermentable fiber from carbohydrates can lead to poor gut health and an increased risk of developing a leaky gut, which can cause significant inflammation. Furthermore, short-chain fatty acids (SCFA) are the metabolic product of fermentable fiber. These SCFA are powerful epigenetic signaling agents that enhance gene transcription. Ketosis generates a different type of hydroxylated short fatty acid (3-hydroxyl butyrate, that has no effect on gene transcription. In addition, the lack of SCFA has significant negative consequences on the gut-brain axis. Cortisol build-up: To produce glucose for the brain, cortisol levels increase to breakdown protein to make sufficient glucose via neoglucogenesis. Excess cortisol can lead to insulin resistance that cause regain of some of initially loss body fat. In addition, increased cortisol levels cause a depressed immune system as well as destruction of memory cells in the hippocampus. The initial benefits of following the ketogenic diet result in some initial weight loss (primarily water weight rather than fat loss), long-term studies show no significant differences in overall weight loss. Now new findings show a ketogenic diet may lead to significant adverse health consequences by accelerating the formation of zombie cells. Call me crazy, but I feel the key to longevity and wellness comes down to better metabolic control instead of living in a constant state of ketosis. Following Metabolic Engineering® for a lifetime provides that pathway of losing body fat without ketosis. References 1. Johnston CS, Tjonn SL, Swan PD, White A, Hutchins H, and Sears B. “Ketogenic low-carbohydrate diets have no metabolic advantage over nonketogenic low-carbohydrate diets.” Am J Clin Nutr 2006 83:1055-61. 2. White AM, Johnston CS, Swan PD, Tjonn SL, and Sears B. “Blood ketones are directly related to fatigue and perceived effort during exercise in overweight adults adhering to low-carbohydrate diets for weight loss: a pilot study.” J Am Diet Assoc. 2007 107:1792-1796. 3. Sung-Jen Wei, Joseph R Schell, E Sandra Chocron, Mahboubeh Varmazyad, Guogang Xu, Wan Hsi Chen, Gloria M Martinez, Felix F Dong, Prethish Sreenivas, Rolando Trevino Jr , Haiyan Jiang, Yan Du, Afaf Saliba, Wei Qian, Brandon Lorenzana, Alia Nazarullah, Jenny Chang, Kumar Sharma, Erin Munkácsy, Nobuo Horikoshi, David Gius. Ketogenic diet induces p53-dependent cellular senescence in multiple organs. Sci Adv. 2024 May 17;10(20):eado1463. doi: 10.1126/sciadv.ado1463. 4. Owen OE, Felig P, Morgan AP, Wahren J, Cahill GF Jr. Liver and kidney metabolism during prolonged starvation. J Clin Invest. 1969 Mar;48(3):574-83. doi: 10.1172/JCI106016. 5. Chriett, S., Dąbek, A., Wojtala, M. et al. Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule. Sci Rep 9, 742 (2019). https://doi.org/10.1038/s41598-018-36941-9. 6. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020 Jan 31;11:25. doi: 10.3389/fendo.2020.00025. 

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050824---Tofu-Blog

Tofu: Tips and Recipes Ideas

I have been eating tofu for a very long time, much longer than the 30 or so years I have been following the Zone Diet. Back then many of my favorite recipes came from the Tassajara cookbooks by Edward Espe Brown, the celebrated chef from the kitchen at California’s famous Zen Mountain Center, and cookbooks by Louise Hagler, a.k.a. Wendy Louise, a well-known authority on vegetarian cooking who is associated with a community in Tennessee known as The Farm. Those books are still among the best resources for tofu recipes. My mantra has always been if you don’t like something, don’t eat it. Keep this in mind if you’re new to tofu, start slowly by combining it with flavors and foods you like.    Tips and Suggestions    Firm-sprouted tofu is my preference for the Zone Diet. Unlike traditional tofu, which contains significant amounts of both protein and carbohydrate, sprouted has almost no carbohydrates. It’s lighter tasting, refreshing, and very filling.   Freezing tofu results in a chewy, sponge-like texture. I don’t recommend freezing, but some people prefer it when using tofu to substitute for meat in a recipe.    Baked tofu comes in a variety of flavors and makes an excellent quick meal with some vegetables and fruit added. It’s also great in salads.     Tofu made it into the book “The Top 100 Zone Foods” by Barry Sears.    Some recipes call for draining the tofu first. I find that usually isn’t necessary.   Tofu takes on the flavor of whatever is added to it.    Add nutritional yeast flakes to give a cheesy flavor to vegan tofu scrambles and dips. It’s also rich in protein and vitamin B12.   Cherry Vanilla Tofu “Ice Cream”   Tip: This doesn’t freeze or store well, so prepare only the amount you plan to serve immediately.   Using an immersion blender or a food processor blend equal parts of frozen dark cherries and firm tofu, plus some vanilla extract (preferably alcohol-free for best flavor). Serve immediately.  Tofu Scramble  This is great for breakfast, lunch, or dinner, and we’ve even brought it on long day hikes for a snack.   Crumble some firm tofu and stir in a generous amount of seasonings, taking care not to overdo it with the salt. Heat in a well-seasoned or nonstick skillet with a little Zone-friendly oil to the desired doneness.    Optional: If time allows, sauté some chopped onion in the skillet before adding the tofu and seasonings.    My favorite seasoning combination for this dish at my house is onion powder, garlic powder, turmeric, paprika, some oregano or thyme, nutritional yeast flakes, salt, and ground black pepper. The yellow color of the turmeric makes it somewhat like scrambled eggs.   Tofu Veggie Almond Pasta Salad   Dressing: Thin some smooth almond butter by stirring in some water, a little vinegar, and either soy sauce or Bragg’s Liquid Aminos (an unfermented soy sauce found in the health food section of most grocery stores).    Toss together cooked Dr. Sears’ Zone PastaRx Fusilli, tofu cut into cubes, matchstick cut red bell pepper, chopped green parts of scallions (a.k.a. green onions), and the almond butter dressing. Serve immediately or chill to serve later. It will keep well in the fridge for two or three days.   Use your imagination and see what you can come up with.  Experiment and have fun with it. Try using tofu to make cheesecakes, whipped desserts, tofu chocolate pudding, tofu “cream” based soups, tofu pot pie (think chicken pot pie), tofu burgers, tofu burritos, Buffalo tofu (like Buffalo wings), layered Mediterranean dips, tofu “meatballs”, grilled tofu, and more.    Enjoy! 

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