Zone Living Articles
What Is An Effective Dose of Omega-3 Fatty Acids?
The November 10, 2018 issue of the New England Journal of Medicine contained two articles on the use of omega-3 fatty acids to treat cardiovascular conditions (1,2). One study (the VITAL trial) used essentially a low dose of omega-3 fatty acids (0.84 grams of omega-3 fatty acids) and found no cardiovascular benefits (1). The other study (the REDUCE-IT trial) used a much higher dose of omega-3 fatty acids (3.8 grams of omega-3 fatty acids) and found significant cardiovascular benefits (2). The FindingsBoth studies used the same endpoint for determining cardiovascular benefits. The low-dose study found no benefits, while the high-dose study found highly significant benefits. This is probably because the omega-3 fatty acid dosage used in the REDUCE-IT trial was 4.6 times greater than that used in VITAL. However, this is far from breaking news. These findings from REDUCE-IT simply confirmed the 2007 JELIS Trial conducted with much larger group of patients (18,000) who were also all taking statins (3). Are There Any Differences Between EPA and DHA? Both studies demonstrated some basic misunderstandings on the mechanism of omega-3 fatty acids and its impact on cardiovascular disease. Both the products used in the studies are only approved to lower very high levels of triglycerides (greater than 500 mg/dL) and not approved for treating heart disease. In addition, one product contained a combination of EPA and DHA (Lovaza) and the other product only contained EPA (Vascepa). Since the REDUCE-IT trial that used the EPA-only product worked, this might imply that DHA is dangerous. This is a story that starts with a statement that EPA lowers LDL cholesterol and DHA raises LDL cholesterol levels and therefore only EPA containing products are useful. That’s a marketing statement that is only partially true. A meta-analysis showed that EPA lowers LDL cholesterol levels by 0.7% and DHA raises LDL cholesterol levels by 2.6% (4). If you have a high LDL cholesterol level of 130 mg/dL, this means using EPA-rich omega-3 supplements will lower your LDL cholesterol by 1 mg/dL and using DHA-rich omega-3 fatty acid supplements will raise your LDL cholesterol by 3.5 mg/dL (4). These changes are clinically meaningless. Furthermore, the same meta-analysis study indicated that DHA-rich omega-3 fatty acid supplements are better than EPA-rich omega-3 fatty supplements in reducing triglycerides and increasing HDL cholesterol. These differential lipid effects between EPA-rich or DHA-rich omega-3 fatty acid products essentially balance themselves and suggest that there are no differences between EPA and DHA in lowering total lipid levels. Both are beneficial. Therefore, it is not the absence of DHA that is important, but the dose used. Lowering lipid levels, however, is not the reason that high-dose omega-3 fatty acids have the benefits in reducing cardiovascular events. The Real Benefits of Omega-3 Fatty Acids It is well established that heart disease is an inflammatory disease (5,6). Much of that inflammation is mediated by pro-inflammatory proteins called cytokines. A recent Harvard study indicated that reducing one of these inflammatory cytokines (IL-1b) using a targeted monoclonal antibody could reduce heart attacks without lowering LDL levels (7). An even earlier trial in 1989 in normal subjects demonstrated that high-dose omega-3 fatty acids (5 grams per day) significantly lowered the levels of a variety of pro-inflammatory cytokines (8). This is why the AA/EPA ratio in the blood is the best marker for determining the reduction of pro-inflammatory cytokine production. But reducing cytokine levels to lower inflammation is dramatically enhanced by the simultaneous increase in a group hormones known as resolvins. Resolvins to the Rescue Omega-3 fatty acids can produce two groups of hormones. One are pro-inflammatory hormones known as eicosanoids and the other is a group of pro-resolution hormones known as resolvins. When it comes to eicosanoids, DHA cannot produce eicosanoids and the eicosanoids produced from EPA are weakly inflammatory. Since the eicosanoids generated from EPA are 10-100 times less inflammatory compared to those generated from AA the end result is that as EPA is increased at the expense of AA in the body. This means the intensity of the inflammatory response is significantly reduced (9). What might appear to be an “anti-inflammatory” effect, is actually a significant reduction of the intensity of overall inflammation. The real benefits of omega-3 fatty acids comes from their production of resolvins. This is why you need both EPA and DHA as each omega-3 fatty acid makes different types of resolvins that interact with different receptors. Furthermore, you need a much higher concentration of both EPA and DHA in the blood to generate the levels of resolvins that are necessary to resolve existing inflammation (10-12). Thus, the real benefits of high-dose omega-3 fatty acids may come from their ability to increase resolvin production as well as the reduction of pro-inflammatory cytokines. This would explain why the low-dose of omega-3 fatty acids used in the VITAL study generated essentially negative results. Unless you generate adequate levels of resolvins and simultaneously reduce cytokines by sufficiently lowering the AA/EPA ratio with high-dose omega-3 fatty acid supplementation, it is unlikely you will have significant clinical benefits. This was demonstrated in the subsequent analysis of the JELIS study when it was demonstrated that only when the AA/EPA ratio had been reduced to a level of less than 1.3 that statistically significant differences in cardiovascular events between the active and control groups become apparent (13). It was also demonstrated in an earlier study that the level of EPA (3.8 grams per day) used in the REDUCE-IT study would lower the AA/EPA ratio to 1.2 (14). Using a lower dose of 1.9 grams of EPA per day, the AA/EPA ratio was only reduced to 2.3. Based on the clinical results of the JELIS and REDUCE-IT studies, it appears that you have to reduce the AA/EPA to less than 1.3 using high-dose omega-3 fatty acid supplementation to see a therapeutic effect in treating cardiovascular disease by a combination of two factors of increasing resolvins as well as lowering cytokine levels. Since you need both EPA and DHA for optimal clinical benefits, I happen to believe a 2:1 ratio of EPA and DHA provides the greatest overall benefits to omega-3 fatty acid supplementation. The REDUCE-IT trial indicates you probably need 4 grams of EPA per day to get a cardiovascular benefit, but that means to get an optimal cardiovascular result you would want another 2 grams of DHA per day or a total of 6 grams of EPA and DHA per day. How Do You Know How Much EPA and DHA to Take? It is virtually impossible to measure either eicosanoids or resolvins in the blood and it is relatively difficult to measure cytokines, but you can easily measure the AA/EPA ratio. The published data from the JELIS and REDUCE-IT trials indicates that to have maximum cardiovascular benefits, the AA/EPA ratio should less than 1.3. This is why you should always test, not guess about your health. Furthermore, don’t believe statements that omega-3 fatty acids have no health benefits. They do, but only if you lower the AA/EPA ratio in the blood to an appropriate range, which requires higher amounts of omega-3 fatty acids to do so (15, 16). {{cta('9a69e3f7-d8f4-4170-b5dd-dacbbf27467a')}} References Mason JE, Cook NR, Lee I-M, Christen W, Bassuk SS, Mora S, Gibson H, Albert CM, Gordon D, Copeland T, D’Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, and Burning JE. “Marine n-3 fatty acids and prevention of cardiovascular disease and cancer." New Engl J Med doi: 10.1056/NEjMoa1811403 (2018) Bhatt DL, Steg G, Mill M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT, Juliano RA, Jiao L, Granowitz G, Tardif J-C, and Ballantyne CM. “Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia.” New Engl J Med doi: 10.1056/NEJMoa 1812792 (2018) Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, and Shirato K. “Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 369: 1090-1098 (2007) Jacobson TA, Glickstein SB, Rowe JD, and Soni PN. “Effects of eicosapentaenoic acid and docosahexaenoic acid on low density lipoprotein cholesterol and the other lipids.” J Clin Lipidol 6:5-18 (2012) Libby P, Ridker PM, and Maseri A. “Inflammation and atherosclerosis.” CirculationMar 105: 1135-1143 (2002) Geovanini GR and Libby P. “Atherosclerosis and inflammation: overview and updates.” Clin Sci 132:1243-1252 (2018) Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, and Glynn RJ. . “Antiinflammatory therapy with canakinumab for atherosclerotic disease.” N Engl J Med 377: 1119-1131 (2017) Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, Cannon JG, Rogers TS, Klempner MS, and Weber PC, Schaeffer EJ, Wolff SM, and Dinarello CA. . “The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells.” N Engl J Med 320: 265-71 (1989) Calder PC. “Omega-3 fatty acids and inflammatory processes: from molecules to man.” Biochem Soc Trans. 2017 Oct 15;45(5):1105-1115. Spite M, Clària J, and Serhan CN. “Resolvins, specialized proresolving lipid mediators, and their potential roles in metabolic diseases.” Cell Metab 19: 21-36 (2014) Elajami TK, Colas RA, Dalli J, Chiang N, Serhan CN, and Welty FK. “Specialized proresolving lipid mediators in patients with coronary artery disease and their potential for clot remodeling.” FASEB J 30: 2792-2801 (2016) See VHL, Mas E, Prescott SL, Beilin LJ, Burrows S, Barden AE, Huang RC, and Mori TA. “Effects of prenatal n-3 fatty acid supplementation on offspring resolvins at birth and 12 years of age: a double-blind, randomised controlled clinical trial.” Br J Nutr 118: 971-980 (2017) Itakura H, Yokoyama M, Matsuzaki M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, and Matsuzawa Y. “Relationships between plasma fatty acid composition and coronary artery disease.” J Atheroscler Thromb 18: 99-107 (2011) Braeckman RA, Manku MS, Bays HE, Stirtan WG, and Soni PN.. “Icosapent ethyl: Effects on plasma and red blood cell fatty acids.” Prostagl Leuko Essen Fatty Acid 89: 195-201 (2013) Sears B. “Omega-3 fatty acids and cardiovascular disease: Do placebo doses give placebo results?” CellR4 5:e2302 (2017) Sears B. “Omega-3 fatty acids and cardiovascular disease: Dose and AA/EPA ratio determine the therapeutic outcome.” CellR4 6:e2531 (2018
Food Journaling and Weight Loss
You might be surprised to learn that one of your biggest assets when it comes to weight loss or weight maintenance is as simple as having a pen and paper. When getting started on a weight loss routine or trying to get through a weight loss plateau keeping a record of everything you eat or drink over the course of the day can be a huge piece of your success. Studies have shown that people who keep food journals can lose twice as much weight as those who don’t (1). Food journals are also helpful to improve food choices and identify deficiencies, food triggers or potential allergens in your diet. How to Start Food Journaling: Find What Works Best For You: There are numerous ways to track, but the key is finding something that works for you. If it’s not easy you won’t stick with it. Sometimes a pen and paper is the best way to jot things down as you go, plus its portable so you can keep on hand. There are also plenty of apps you can access too for easy tracking. Record Everything: No matter how big or small write-it down. It’s the little things that add up like beverages, condiments, eating leftovers when cleaning up from dinner or the candy on your co-workers desk. Track after Your Meal: Try and record everything you eat as close to meal time as possible. If you wait until the end of the day you’ll be likely to forget what you had or estimate incorrectly so write as you go. Be Accurate: Having a food scale or measuring cups and spoons may be helpful to ensure your portions sizes are accurate. We often over estimate our portions so this is a good place to start. This is especially helpful if you feel as though you've been doing everything right and the scale doesn't seem to budge. You don’t have to keep this up long just until you get comfortable that you are estimating correctly. If you aren’t home to weigh things out, use the nutrition facts panel as a guide or many restaurants have their calorie information posted online. Getting acquainted with these portions sizes can help too. Write How You Feel and Time of Day: When we are tired, irritable, emotional or stressed that is when we are more likely to throw the towel in on healthy eating. When tracking your intake make a note of how you feel. This can be a note about what made you eat (tired, boredom, stress) or how the meal itself made you feel (tired, fatigued, energetic). This gives you the insight to know what your triggers are and how to better navigate them moving forward. If You Cheat, Track It: If you’ve completely overindulged, it’s ok, just write-it down. There is no guilt here, just get back on track at your next meal. You gain the most insight when you log your cheat meals as it allows you to track how frequently the indulgences occur. Logging also increases the likelihood that your next meal will be healthier, rather than forming a new pattern of poor choices. {{cta('daffa570-1055-4766-af51-e09d66a17e47')}} Keeping a food journal keeps you accountable for your food choices. If you have to write down a poor food choice, you’ll be less apt to put it in your mouth. Whether you’re just starting on your weight loss journey, trying to maintain your current weight or want to identify food cravings, journaling is great way to identify patterns, cravings and how your emotional triggers influence your food choices. References: Hollis JF, Gullion CM, Stevens VJ, Brantley PJ, Appel LJ, Ard JD, Champagne CM, Dalcin A, Erlinger TP, Funk K, Laferriere D, Lin PH, Loria CM, Samuel-Hodge C, Vollmer WM, Svetkey LP; Weight Loss Maintenance Trial Research Group. Weight loss during the intensive intervention phase of the weight-loss maintenance trial. Am J Prev Med. 2008 Aug;35(2):118-26. doi: 10.1016/j.amepre.2008.04.013.
Three Hormones That Could Be Impacting Your Weight
Many of the problems that prevent us from reaching our weight loss goals are due to hormonal imbalance. If you are careful about your food choices, exercise regularly and still aren't seeing the scale budge, your hormones may be to blame. When trying to reach the Zone, you’ll often hear us talk about the importance of hormonal control. When our hormones are unbalanced it can accelerate the aging process, decrease our overall wellness, and hinder our ability to perform or maintain our weight. Here we’ll focus specifically on hormones that might be impacting your weight and what you can do to manage them. What are hormones? For many of us, our first introduction to the word hormones was somewhere in our early teens. While it may be a word that is familiar to us, defining it could prove more challenging. Hormones are chemical messengers that travel in our blood, tissues and organs helping with communication throughout our body. While they do impact growth, development and the aging process they also play a critical role in how our body gets energy from the foods we eat, known as metabolism. Hormones are powerful in that small amounts produce big changes within our bodies (1). This is why the foundation for reaching the Zone is based upon using the foods we eat and supplements we take to control our hormones. Hormones and Weight Dr. Sears has written about this extensively, but the real reason we gain weight is not due to insulin per se, but increased insulin resistance. Insulin resistance is caused by increased inflammation in our insulin-sensitive cells. This makes it difficult for insulin to communicate its message to its target cells in the liver, muscles, and adipose tissues. Increased insulin resistance forces the pancreas to produce even more insulin to try to get that message to the target cell in an effort to respond. As a result, insulin levels rise in the blood and stay constantly elevated. In the case of the fat cells in the adipose tissue, these constantly elevated insulin levels drive circulating fat into your existing fat cells and block the release of stored fat. This makes it difficult to lose weight. The Solution: To optimize your insulin levels for fat loss requires following an anti-inflammatory eating plan like the Zone Diet which is based upon controlling insulin levels at every meal and snack. This is achieved by balancing the protein-to carbohydrate ratio at each meal coupled with the use of small amounts of monounsaturated fats know to be anti-inflammatory. Since diet is one of the main reasons we develop insulin resistance, it’s also one of the easiest changes we can make to help reverse it. Adiponectin is a protein hormone that plays a role in insulin resistance. Individuals who are overweight, obese or have high levels of insulin resistance have been shown to have low levels of adiponectin. The leaner you are, the more circulating adiponectin you have which is strongly correlated with decreased insulin resistance in the fat cells. It is thought that adiponectin works by increasing fatty acid oxidation leading to improvements in insulin sensitivity (2). The Solution: In addition to an anti-inflammatory diet to help reduce insulin resistance and keep adiponectin levels high, supplementation with omega-3 fatty acids has been shown to increase circulating levels of adiponectin (3) as well as exercise (4). Cortisol is a hormone that the body produces under stress and can hinder our ability to lose weight. You need some cortisol, but where you run into issues is when the body is producing excessive amounts. In addition to stressful conditions we might be under in our day to day lives, excessive exercise, fasting, inflammation, and excess insulin can increase cortisol production. Cortisol is produced during fasting conditions when energy stores are depleted. During this time blood glucose and insulin levels begin to drop and as a result cortisol is released. Cortisol levels naturally rise in the morning, but its release signals the body to begin breaking down muscle for energy. This is why it’s critical to eat an appropriate breakfast coming off an overnight fast to restore blood sugar levels and replenish glycogen and to avoid skipping meals. In addition, when we have too much insulin circulating in our bodies it can drive down blood glucose levels resulting in the increased cortisol levels and making it difficult for it our bodies to release stored fat. The Solution: There a number of ways to reduce cortisol. One is to follow the Zone Diet to reduce diet-induced inflammation. The second is to resolve inflammation using high-dose omega-3 fatty acids. The third is to use polyphenols which help repair tissue damage caused by inflammation. The three of these together form the basis for the Zone Pro-Resolution Nutrition Program. Finally, there is the traditional way using stress reduction. Stress reduction can include meditation, relaxation, or moderate exercise (too intense can actually increase cortisol) to help reduce excess cortisol levels by reducing the activation of the sympathetic nervous system. Many of the problems that prevent us from reaching our goals are due to hormonal imbalance. The Zone Pro-Resolution Nutrition program consisting of the reduction, resolution, and repair of diet-induced inflammation is your best pathway to get to the Zone and make your goals a reality. {{cta('61bf66d9-5561-4209-b869-f696d6532948')}} References Available at: https://medlineplus.gov/hormones.html. Accessed: September 6, 2018. Lihn AS1, Pedersen SB, Richelsen B. Adiponectin: action, regulation and association to insulin sensitivity. Obes Rev. 2005 Feb;6(1):13-21. Wu JH, Cahill LE, Mozaffarian D. Effect of fish oil on circulating adiponectin: a systematic review and meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2013 Jun;98(6):2451-9. Markofski MM, Carrillo AE, Timmerman KL, Jennings K, Coen PM, Pence BD, Flynn MG. Exercise training modifies ghrelin and adiponectin concentrations and is related to inflammation in older adults. J Gerontol A Biol Sci Med Sci. 2014 Jun;69(6):675-81.
Intermittent Fasting vs The Zone Diet
Abstaining from food and beverage, other than water, for a period of time (a.k.a fasting) has been used since the beginning of time out of necessity for survival, spiritual reasons, and health promotion. Intermittent Fasting (IF) is an eating pattern that goes between days of fasting or partial fasting and eating. IF has become increasing popular in the health and fitness arena for its perceived role in weight loss and improved health. Here we’ll tell you more about it and give you Dr. Sears’ take on this old concept but new trend. What is Intermittent Fasting? Calorie restriction is the reduction of calorie intake without compromising nutrition. Calorie restriction has been shown to be the most effective way to help slow down the aging process. A recent study showed that restricting calories over a two year period of time slowed metabolism and reduced oxidative stress, two key pieces for reducing the rate of aging and protecting against age-related disease (1). Intermittent fasting (IF) tries to replicate the benefits of calorie restriction, without having to continuously restrict calories. The idea being that not restricting calories daily makes compliance easier to follow. IF involves restricting calories 1-3 days per week and then eating as you normally would on your non-restricted days. There are several approaches to Intermittent Fasting but the premise is you eat normally a few days a week and drastically cut back on calories the other days. This form involves a day in which food and beverages (other than water) are completely restricted followed by a day where foods and beverages can be consumed normally. There are variations within alternate day fasting as well. A more scientifically investigated form involves eating 25 percent of your needed calories on one day and then 125 percent of your needed calories on the next day. The total calorie intake would be 75 percent of needed calories (2). Some calories can be consumed on fast days but it’s severely restricted to 20-25% of your energy needs (approximately 500-600 calories). This is the basis for the 5:2 diet where you restrict energy two non-consecutive days and then eat normally the other 5 days. This involves daily fasting intervals ranging from 12-20 hours. Religious fasts often use time-restricted feeding (i.e. Ramadan). The Science The science on calorie restriction (CR) itself is strong, but what about using the IF approach to calorie restriction? Many of the benefits of intermittent fasting such as improved metabolic profiles, decreased weight and reduced risk for chronic disease have been widely studied in animals. Despite the success of those studies, the same benefits are mixed when it comes to human trials (3), which may be related to compliance. In studies comparing similar caloric intake using both IF and CR there are no differences between the two groups in either weight loss, improvements in blood markers (glucose, insulin, lipids, inflammation) and chronic disease risk (4). Both may be equally effective for weight loss and cardio-protection. In one series of carefully controlled long-term trials (the CALERIE studies), the goal was to have individuals reduce calorie intake by 25 percent on a continuous basis. Even though individuals could only reduce their intake by 15% these calorie restricted (CR) experiments demonstrated significant clinical benefits (1). The data is clear that if you can restrict calories there are benefits to be gained. Intermittent Fasting vs. The Zone Diet Intermittent fasting is based on the idea that continuous calorie restriction is too hard to follow for the lifetime. So maybe you can do it for a couple of days with fasting or mini-fasts, knowing you can eat normally or overeat the next day or every other day. Regardless of the approach used, the answer appears to be that there is no benefit of intermittent fasting compared to consuming the same number of restricted calories day in and day out according to recent studies. Furthermore, there is no difference in weight loss between a continuous calorie–restricted diet and an intermittent fasting diet because the weekly intake of calories consumed is about the same. However, subjects in these studies using intermittent fasting tend to be less compliant as they are hungrier on their fasting days. The key to the Zone Diet is not simply the restriction of calories, but the constant maintenance of hormonal balance that results in stable blood glucose levels so that you are not hungry between meals. After all, who wants to be hungry no matter what the potential health benefits may be. In addition, if you use Ramadan as an example in which observant Muslims who fast all day and then only eat after the sun goes down, you see that they do lose weight, but the lost weight is all regained shortly after the fasting period is over. This isn’t ideal for long-term health benefits. In addition 16 hour fasts may place stress on your bodies hormonal systems as one may run the risk of upsetting the hormonal levels like insulin, glucagon, and cortisol. The Zone Diet is built upon the concept of calorie restriction coupled with hormonal balance, so that you are never hungry or fatigued and can easily follow it for a lifetime. Following a calorie restricted Zone Diet will yield many of the clinical positive benefits often attributed to various forms of fasting but with greater long-term compliance.{{cta('a8225404-c675-40b7-8eaa-4836beb805da')}} References: 1. Leanne M. Redman, Steven R. Smith, Jeffrey H. Burton, Corby K. Martin, Dora Il'yasova, Eric Ravussin. Metabolic Slowing and Reduced Oxidative Damage with Sustained Caloric Restriction Support the Rate of Living and Oxidative Damage Theories of Aging. Cell Metabolism, 2018.2. Trepanowski JF, Kroeger CM, Barnosky A, Klempel MC, Bhutani S, Hoddy KK, Gabel K, Freels S, Rigdon J, Rood J, Ravussin E, Varady KA. Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. JAMA Intern Med. 2017 Jul 1;177(7):930-938. 3. Horne BD, Muhlestein JB, Anderson JL. Health effects of intermittent fasting: hormesis or harm? A systematic review.Am J Clin Nutr. 2015 Aug;102(2):464-70. 4. Patterson RE, Laughlin GA, LaCroix AZ, Hartman SJ, Natarajan L, Senger CM, Martínez ME, Villaseñor A, Sears DD, Marinac CR, Gallo LC.Intermittent Fasting and Human Metabolic Health. J Acad Nutr Diet. 2015 Aug;115(8):1203-12