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Omega-3 Fatty Acids and Blood Pressure

The FDA recently announced limited health claims for the use of omega-3 fatty acids in the treatment of hypertension and heart disease.  These are qualified health claims since each of the allowed claims must carry the following language, “FDA has concluded that the evidence is inconsistent and inconclusive”.  Nonetheless this indicates the FDA is beginning to acknowledge that omega-3 fatty acids have potential in the treatment of hypertension and cardiovascular disease. These health claims can only be used if a single-serving size contains at least 0.8 g of EPA and DHA.

It took more than five years of study by the FDA to even allow these limited health claims as the petition for them was launched in 2014.  The primary scientific document that used was a meta-analysis of various clinical trials published in the American Journal of Hypertension (1).  More than 70 clinical trials were included in the analysis.  Although the average reduction in systolic blood pressure by 1.5 mm Hg and diastolic blood pressure by 1 mm Hg was seemingly small, the effects in untreated hypertensive subjects was far greater (4.5 mm Hg reduction in systolic pressure and 3.1 mm Hg reduction in diastolic pressure).  Furthermore, the reduction in the diastolic pressure was only observed if the daily dose of EPA and DHA was greater than 2 grams per day.  Ironically, a lower dose of EPA and DHA between 1 and 2 grams per day had no effect on diastolic blood pressure.  Therefore, it seems that the FDA qualified health claim would be far stronger if the minimum omega-3 dosage was greater than 2 grams per day as opposed to the stated 0.8 grams per day.  Of course, there might be a problem since at those levels of daily EPA and DHA, intake of commercially available omega3s may contain too many toxins such as PCBs.

The benefits of a higher dose of EPA and DHA for treating hypertension has been confirmed in more recent studies (2,3). In these studies, there were equivalent drops in systolic blood pressure at 0.7 and 1.8 grams of EPA and DHA per day, but the higher dose (1.8 grams per day) had a drop in diastolic pressure, but not with the lower dose (0.7 grams per day) (4).

This differential effect of omega-3 fatty acids on risk of heart disease was illustrated in two recent trials (5,6).  At a low dose of 0.8 grams of omega-3 fatty acids per day, there was no clinical benefits.  At a higher dose of 3.9 grams of omega-3 fatty acids, there was a strong cardiovascular benefit.  Further analysis of the high-dose omega-3 data indicated that among statin-treated individuals, the addition of the high-dose omega-3 fatty acids reduced the occurrence of a first heart attack, secondary heart attack, and total ischemic events by approximately 30 percent compared to statins alone (7).  As pointed out in a recent commentary by me, the appropriate dose of omega-3 fatty acids are best measured by the reduction in the arachidonic acid (AA) to eicosapentaenoic acid (EPA) ratio in the blood (8).  Unfortunately, the AA/EPA ratio was not reported in any of the hypertension or cardiovascular trials.

Hopefully future clinical investigators will use the levels of omega-3 fatty acids required to reach an appropriate AA/EPA ratio (1.5 to 3) to obtain much stronger research findings so that the health claim for omega-3 fatty acids in hypertension and cardiovascular disease is not followed by the qualifier, “FDA has concluded that the evidence is inconsistent and inconclusive” .

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  1. Miller PE et al. “Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure:  A meta-analysis of randomized controlled trials.”  American Journal of Hypertension 27:885-896 (2014)
  2. Yang B et al. “Lowering effect of n-3 fatty acid supplements on blood pressure in Inner Mongolia hypertensive patients.”  J Agric Food Chem 67: 184-192 (2019)
  3. Casanova MA et al. “Omega-3 fatty acids supplementation improves endothelial function and arterial stiffness in hypertensive patients with hypertriglyceridemia and high cardiovascular risk.”  J Am Soc Hypertension 11; 10-19 (2017).
  4. Minihane AM et al. “Consumption of fish oil provide eicosapentaenoic acid and docosahexaenoic acid reduces blood pressure in adults with systolic hypertension.” J Nutr 146: 516-523 (2016)
  5. Manson JE et al. “Marine n-3 fatty acids and prevention of cardiovascular disease and cancer.”  N Engl J Med 380: 23-32 (2019)
  6. Bhatt DL et al. “Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia.” N Engl J Med 380: 11-22 (2019)
  7. Bhatt DL et al. “Effects of icosapent ethyl on total ischemic events.”  Am Coll Cardiol 73: 2791-2802 (2019)
  8. 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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