Triglyceride versus Ethyl Ester Fish Oil
Fish oils are more common in the consumer marketplace which requires individuals be more educated about what they are consuming. This isn’t as easy as you think if you don’t know what to look for. In this blog, Dr. Sears explores fish oil purity and what to know about the difference between ethyl esters and triglycerides. The Growth of the Fish Oil Market Before 2001 the sales of fish oil products in the United States were minimal. Prior to 2001, most of what was sold at that time consisted of the same cod liver oil that your great-grandparents gave your grandparents before they could leave the house each morning. It tasted terrible because it wasn’t purified and required having to take a tablespoon daily because it wasn’t very concentrated since it was derived from extracted cod livers. All of that changed starting in 2002, as shown by this graph taken from the Washington Post. In 2001, I wrote extensively about this change in my book The OmegaRx Zone: The Miracle of the New High-Dose Fish Oil. I described the breakthroughs taking place in the processing of omega-3 fatty acid concentrates and how this could eventually usher in a new era of medicine. Yet less than eight percent of American adults were consuming fish oil supplements by 2012 (2). Why Not Just Eat Fish? Consuming fish solely as a source of omega-3 fatty acids in the diet sounds good in theory, but what is considered an acceptable level of intake? The goal should be to consume enough omega-3 fatty acids to deliver at least 2.5 grams of EPA and DHA daily. You require those levels because omega-3 fatty acids are essential nutrients the body cannot make, and the diet must supply them. If you were to translate 2.5 grams of EPA and DHA into fish consumption, that would be about 40 oz. of canned tuna or 8 oz of canned salmon daily. Unfortunately, the types of fish that Americans prefer to eat are lean fish that have minimal amounts of EPA and DHA. Furthermore, fish don’t make omega-3 fatty acids; they accumulate them from marine sources (such as plankton) that can produce them. Unfortunately, another downside to consuming large quantities of fish is that they accumulate toxins that we have thrown into the oceans, such as polychlorinated biphenyls (PCBs). Without adequate levels of EPA and DHA, it is impossible to control inflammation in every organ in the body. Currently, the average American consumes about 100 mg of EPA and DHA. Unfortunately, those are deficient levels resulting in an increase in inflammation-driven diseases over the past 20 years. How EPA and DHA are increased in fish oils To increase the concentration of EPA and DHA found in crude fish oils and reduce the PCBs found in all fish oils, you must convert crude fish oil into ethyl esters and then concentrate the EPA and DHA by molecular distillation. You can’t do that with the natural triglycerides found in crude fish oils that you consume eating regular fish. Once you convert crude fish oils into a high-potency omega-3 fatty acid ethyl ester, they become exceptionally prone to oxidation. Some manufacturers reassemble the purified ethyl esters back into triglycerides. Unfortunately, this synthetic step causes increased oxidation and the repositioning of EPA and DHA from their natural position into unnatural configurations in reconstituted triglycerides. These reconstituted fish oils are essentially “Frankenstein fats” that make it difficult for the body to convert the omega-3 fatty acids into phospholipids which are the final depots for omega-3 fatty acids in the body. What To Know When Choosing an Omega-3 Omega-3 fatty acids are essential for human health, but only if they are purified from PCBs, not oxidized, and easily converted into phospholipids for long-term storage. Let’s start with PCBs. PCBs are never completely removed from an omega-3 fatty acid concentrate, but depending on the refining technology, they can be reduced to very low levels. At Zone Labs, we only use selected lots of crude fish oil processed to have incredibly low PCB levels. As a result, we have the most rigid standards for the upper limits of PCBs (less than two parts per billion (2 ppb) all 209 PCB isomers) for any company, including drug companies. Furthermore, we test every finished lot of our final product used by the consumer and post the results on our website. Another major problem is oxidative stability. Any processing of crude fish oil will cause increased oxidation leading to rancidity. Rancidity is measured by a standard test known as TOTOX which measures the levels of peroxides, aldehydes, and ketones in the final product you purchase. TOTOX levels govern all edible oil trading in the world. If the TOTOX level of any oil is greater than 26 milliequivalents/kg, it is considered unsuitable for human consumption. You can also smell these oxidation products, so even the freshest fish begin to smell. As you might expect, omega-3 fatty acid concentrates are more prone to oxidation. To get around that smell problem, some manufacturers add lemon flavors to their products. This dramatically increases the TOTOX levels in the finished product that you purchase. If a fish oil product has a lemon taste and smell you can likely assume its TOTOX levels are far greater than the upper limit of 26 milliequivalents/kg, and it is not suitable for human consumption. Safety of Ethyl Esters Virtually all long-term clinical studies of the safety of omega-3 fatty acids have been done with ethyl esters. These ethyl esters are ultimately converted into phospholipids that can be measured in the blood (3 ). A recent study has demonstrated that the higher the omega-3 fatty acids in the phospholipids in the blood, the lower the levels of cardiovascular disease and mortality (4). This is also true of chronic kidney disease (5). Of course, those benefits will only be obtained if the omega-3 fatty acid product quality going into the patient is suitable for human consumption. This is why we pride ourselves in having the omega-3 fatty acids products with the lowest levels of PCBs and TOTOX compared to any company worldwide, including the largest drug companies. References Sears B. The OmegaRx Zone. Regan Books. New York, NY (2001) Clarke TC, Black LI, Stussman BJ, Barnes PM, Nahin RL. Trends in the use of complementary health approaches among adults: United States, 2002-2012. Natl Health Stat Report 2015:1-16. 3, Browning LM, Walker CG, Mander AP, West AL, Madden J, Gambell JM, Young S, Wang L, Jebb SA, Calder PC. Incorporation of eicosapentaenoic and docosahexaenoic acids into lipid pools when given as supplements providing doses equivalent to typical intakes of oily fish. Am J Clin Nutr. 2012 Oct;96(4):748-58. doi: 10.3945/ajcn.112.041343. Harris WS, Del Gobbo L, Tintle NL. The Omega-3 Index and relative risk for coronary heart disease mortality: Estimation from 10 cohort studies. Atherosclerosis. 2017 Jul;262:51-54. doi: 10.1016/j.atherosclerosis.2017.05.007. Ong KL, Marklund M, Huang L, Rye KA, Hui N, Pan XF et al. Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease: pooled analysis of 19 cohorts. BMJ. 2023 Jan 18;380:e072909. doi: 10.1136/bmj-2022-072909.
Stress and Omega-3 Fatty Acids
It’s common knowledge that stress can be a killer. But what is not clear is why is it harmful and what you can do to reduce it? A new research article provides more insight into both questions (1). The subjects in this study were middle-aged, overweight healthy adults. Thirty days before the trial, the subjects were split into three groups consuming either placebo capsules, 1.25, or 2.5 grams of EPA and DHA daily. The stress they were exposed to was being given 10 minutes to prepare a 5-minute speech. This speech entailed telling why they were the best candidates for a job. Furthermore, the speech was delivered in front of two live judges wearing white lab coats who were told to keep neutral facial expressions during the speech. The subjects couldn’t use any notes for their job interview speech in front of the judges. If they didn’t use their allotted 5-minute time, they were told to continue speaking until their five minutes were up. If that wasn’t enough stress, they also had to immediately do an oral 5-minute serial subtraction test after their speech before the same judges. If they made a mistake, they would have to start over from the beginning. This test is known as the Trier Social Stress Test, which produces stress and inflammation (2). About one and half hours before this stress test, the subjects had their blood drawn for cytokine levels and saliva for cortisol levels. Then, they ate a standardized breakfast and then answered a questionnaire on their current state of anxiety. After the 20-minute stress test, the same parameters were measured several times over the next two hours. What happened? Quite a lot. Those taking the 2.5 grams of EPA and DHA per day had significantly lower cortisol levels during and for the next two hours after the test. They also had lower pro-inflammatory cytokine levels and less inhibition of the telomerase enzyme activity that repairs damage to your DNA caused by stress. Similar results of lowered cytokine levels were found in a study of elderly, obese healthy adults taking 2.5 grams of EPA and DHA per day (3). So, what are the implications? If you are in a high-stress occupation, then taking adequate daily levels of EPA and DHA can be your best defense against the inflammation and damage to your DNA that comes with that occupation-induced stress. This group would also include elite athletes who live in a world of constant stress due to training and competition. However, most of us live with chronic low-level stress. The impact of this type of stress on the immune system is the same. It is unlikely that stress will be eliminated in our lives. Still, you can significantly reduce the inflammatory and genetic consequences of that stress by taking adequate EPA and DHA levels on a lifetime basis. References Madison AA et al. Omega-3 supplementation and stress reactivity of cellular aging biomarkers. Mol Psychiatry doi:10.1038/s41380-021-01077-2 (2021) Allen AP et al. Biological and psychological markers of stress in humans: Focus on the Trier Social Stress Test. Neurosci Biobehav Rev 38: 94-124 (2014) Tan A et al. Supplementation with eicosapentaenoic acid and docosahexaenoic acid reduces high levels of circulating pro-inflammatory cytokines in aging adults. Prostaglandins Leukot Essent Fatty Acids 132:23-29 (2018)
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
Fats Explained-What Is Fat And Why Do We Need It?
In the early 90s dietary fat was considered a “villain” and carbohydrates were the “heroine”. The thinking was that by lowering fat in the diet you could decrease the risk of heart disease. Many began to believe that eating fat, made you fat. As a result the food industry began replacing fat with carbohydrates in food products leading to greater consumption of low-fat, high-sugar foods (think Snackwells cookies). Guide to Fat While fat does provide more calories per gram (9kcal/gram) compared to carbohydrate and protein (4kcals/gram), we now know it’s not as simple as swapping out one ingredient for another. In fact there are many benefits to be gained by consuming the right types of fat, the key is moderation. Here we’ll break down what fats are, why you need them, and what to know when choosing them. What is Fat and Why We Need It? Fat is a major energy source for producing energy (ATP) as needed in the body (9kcal/gram) Involved in cell signaling and gene expression An important regulator of inflammation, insulin action, and brain function Sends hormonal signals to the brain saying you are full and satisfied Slows the rate at which carbohydrates enter the blood stream, helping to minimize spikes in blood sugar Helps with the absorption of fat-soluble vitamins (A,D,E,K) Major contributor to cell structure and function Types of Fat Monounsaturated Fat (Omega-9): Monounsaturated fats are fatty acids that contain one (mono) double bond and are liquid at room temperature. These fats can be made by our body, making them non-essential nutrients. You might also hear them referred to as omega-9 fats. Monounsaturated fats are considered “good fats” as their intake may help to promote a healthy heart. Sources: Oils (Olive oil, high-oleic safflower and sunflower oil), avocado, and nuts.{{cta('25ec2a28-187f-4376-8d99-d9c3a928be8e')}} Polyunsaturated (Omega-3 and Omega 6 Fats): Polyunsaturated fats include both omega-6 fatty acids and omega-3 fatty acids. Going back to chemistry these fatty acids contain more than one (poly) double bond and are liquid at room temperature. Polyunsaturated fats are considered essential, meaning they must be supplied by our diet as our bodies can’t make them on their own. Omega-6 Fats: Linoleic Acid is an essential omega-6 fat that has the ability to be made into Arachidonic Acid, a precursor to hormones (prostaglandins, thromboxanes and leukotrienes) linked to inflammation. You need small amounts in the diet, but overconsumption can lead to increased levels of inflammation. Since many processed foods are made with vegetable oils rich in omega-6 fats, most Americans are overconsuming these fats in their diets. Sources of omega-6 fatty acids: nuts, seeds, vegetable oils (sunflower, corn, cottonseed, soybean) Omega-3 Fats Alpha-linolenic acid (ALA) is an essential omega-3 fat (found flaxseed, canola oil, nuts) that has the ability to be converted into EPA and DHA. EPA and DHA have been widely studied for their anti-inflammatory benefits. Only about 1-10% of the omega-3s in ALA are converted into EPA and DHA, so to reap the most benefits it’s important to get EPA and DHA directly through fish and fish oils. Sources of omega-3 fatty acids: Fatty fish and fish oil, nuts, flaxseed. Saturated Fats: Saturated Fat can be made in the body (non-essential) and can be used for structural and metabolic functions. Intake of saturated fat should be limited as higher consumption has been linked to the risk of heart disease. Studies show that replacing saturated fats with mono and polyunsaturated fats may reduce the risk of heart disease. Sources: Whole milk, cream, butter, cheese, meat and oils (coconut oil, palm oil, and palm kernel oil). Trans-Fat: Trans-fats can occur naturally in animal products (milk, butter, cheese, meat), but the majority of trans-fat in our diet comes from the manufacturing process. This is done through a process called hydrogenation where hydrogen is added to vegetable oil, making them go from a liquid at room temperature to a solid. You’ll often see trans-fats listed on labels in the form of partially hydrogenated oils. As of June 18, 2018 trans-fats can no longer be produced, but you may still see them in marketplace through the start or 2020 to give manufacturers time to get them out of circulation. Trans-fats have been shown to be detrimental to health as their intake has been associated with increased levels of LDL (“bad”) cholesterol and the risk for heart disease. Intake should be avoided. Sources: Listed as "partially hydrogenated vegetable oil", found in many processed foods and most bakery products (cookies, cakes, crackers and pastries). Fat Recommendations for the Zone Diet We recommend fat consumption come primarily from heart-healthy monounsaturated fat and anti-inflammatory omega-3 fats rich in EPA (Eicosapentaenoic Acid) and DHA (Docosahexaenoic Acid). Simultaneously we suggest reducing the consumption of vegetable oils rich in omega-6 fats, and avoid intake of fats rich in arachidonic acid, known to be pro-inflammatory. When making a Zone meal we recommend aiming for one that is under 12 grams of fat with 25 grams of protein, about 35 grams of net carbs (total carbohydrates minus fiber) and approximately 400 calories or less. When you have the right amount of fat, balanced with protein and low glycemic carbohydrates, it helps minimize hungry and fatigue for up to 4-5hours. How Much Omega3 Should You Be Getting Each Day EPA and DHA are the two omega-3 fatty acids that have been most widely studied in the literature for their clinical benefits in lowering inflammation. Dr. Sears recommends individuals consume at least 3000mg of EPA and DHA daily for wellness. It would be difficult to meet this recommended intake of EPA and DHA from eating fish alone. While there are benefits to consuming fish, the current recommendations for adults (excluding pregnant woman and children) is to consume no more than 12 ounces of fish per week to minimize intake of contaminants like mercury, polychlorinated biphenyls (PCBs), and dioxins. This is why we recommend OmegaRx 2 as it’s highly purified to remove as many PCBs as possible making it your best choice for purity and potency. Try our zesty avocado dip as a dressing or on the side with chicken and spinach salad. Instructions: In a blender blend together avocado, mango and lime juice. Grill the chicken breast and top with avocado dressing (or on the side). Serve with spinach salad topped with Zoned Herb Dressing (made ahead of time) and Brussels sprouts drizzled with extra virgin olive oil, salt and pepper.
Dr. Barry Sears Answers Your Questions on Omega-3 Fish Oil
Dr. Sears answers some of the top questions we receive about fish oil and omega-3 fatty acids and what makes OmegaRx 2 unique. What are EPA and DHA?EPA is an abbreviation for the omega-3 fatty acid Eicosapentaenoic Acid. DHA is short for Docosahexaenoic Acid. The anti-inflammatory properties of fish and fish oil are mainly due to these two omega-3 fatty acids. The benefit of EPA and DHA comes from reducing cellular inflammation by inhibiting the formation of inflammatory hormones (e.g. eicosanoids) derived from the omega-6 fat, Arachidonic Acid (AA). However, their greatest benefits come from the generation of pro-resolution hormones (i.e. resolvins) that turn off the inflammatory process. If someone considers themselves healthy, why would they need to take omega-3 fatty acids?Omega-3 fatty acids are considered essential fatty acids meaning they must be supplied in our diets. They are the building blocks for hormones that resolve existing inflammation. Unresolved inflammation is the primary reason we gain weight, develop chronic disease, and age at a faster rate. The typical American diet is very low in omega-3 fatty acids and rich in omega-6 fatty acids (the building blocks for pro-inflammatory hormones). This is why you need a high concentration of purified omega-3 fatty acids to make a difference in addition to lowering the levels of omega-6 fatty acids in the diet. Why is fish oil superior to krill oil, flaxseed or other omega-3 products on the market?Fish oil is made by heating fish to release the stored fats. From this crude fish oil, the omega-3 fatty acids can be further refined/purified into omega-3 concentrates. Krill oil is actually made of small shrimp that have been harvested and extracted using harsh chemicals (hexane and acetone). Furthermore, the omega-3 fatty acid content in krill oil is much lower than in omega-3 concentrates derived from fish oil. Flax seed oil is rich in alpha-linolenic acid (ALA). Although ALA is an omega-3 fatty acid, it has no health benefits unless converted into EPA and DHA. This conversion is very inefficient (about 1-10%) so you would have to consume large quantities to get the same benefits of a much smaller amount of omega-fatty acid concentrates. What is it about OmegaRx2 that makes it different from other brands?The answer is purity and potency. OmegaRx 2 is highly purified to remove as many PCBs as possible and our standards are eighteen times more rigid than the industry standards. In addition, Zone Labs publishes the purity data for every lot of OmegaRx 2 on our website to give our customers total transparency. All omega-3 fatty acids are prone to oxidation which is why we publish the levels of stability (defined by the TOTOX level or rancidity in layman terms) on every lot of OmegaRx2 as well. Our post production levels of rancidity are among the lowest on the market. Finally, the concentration of OmegaRx 2 is among the highest concentration of any non-prescription omega-3 fatty acid product on the market. How much fish oil do you recommend people take?I recommend taking a daily minimum of 3 grams of EPA and DHA. That said, we use our Cellular Inflammation test to determine the ideal amount an individual requires. This test looks at the ratio of two key fatty acids in the blood: Arachidonic Acid (AA), an omega-6 fatty acid which is the building block for pro-inflammatory hormones, and EPA which is the building block for pro-resolution hormones. The AA/EPA ratio or Cellular inflammation Score will tell you with the most precision how much you need to take on a daily basis to optimize your overall wellness. It has been demonstrated that decreasing the AA/EPA ratio is strongly associated with a longer life. If my cellular inflammation score is ideal, do I need the heightened concentration? If your Cellular Inflammation Score is between 1.5 to 3 you are in the ideal range to promote future wellness. The higher the Cellular Inflammation Score, the more inflamed you are. The average American has a Cellular Inflammation Score of 20. Resolution of inflammation is key to maintaining wellness, and this can only be achieved with a lower score. It is possible to achieve an ideal AA/ EPA ratio or Cellular Inflammation Score within 30 days with the correct dosage of OmegaRx 2. When will people start seeing the benefits after they begin to supplement and what will they be?I generally tell people that it takes about 30 days to truly see the impact of supplementation in the blood, but it's only a matter of days that their benefits subside once you stop taking them. This means you have to be consistent with your intake of purified fish oils and take it daily. Omega-3 fatty acids have been shown to help support a healthy heart, brain function, behavior and mood regulation, cellular rejuvenation, athletic performance and recovery, and improved vision. Their benefits are due to their role in resolving excess cellular inflammation. Do you have tips for how to take it? Most people do just fine taking our recommended dose of 4 capsules or 1 teaspoon of OmegaRx 2 daily. I always suggest taking it with food and if you want to split up your dose between morning and night to see how you do that is fine too. How long do you have to take it?For a lifetime if you want to maintain wellness. Once you stop taking omega-3 fatty acids your levels of omega-3s will soon return to baseline within a few days. What are the benefits of omega-3 fatty acids across the lifespan? Fish oil or omega-3 fatty acids are critical across the lifespan. This is why they are essential nutrients. It starts in the womb as they support brain development in utero in addition to minimizing post-partum depression for the mother. We now know that the dietary and metabolic environment the fetus is exposed to in the womb can echo through the rest of his or her so it’s critical to have good nutrition and adequate levels of omega-3s throughout pregnancy and after. The rise in conditions such as autism, ADHD, diabetes and heart disease in early childhood and young adulthood may have a connection with the high levels of omega-6 fatty acids in our diet and low amounts of omega-3s. I strongly believe that chronic conditions associated with aging such as heart disease, diabetes, cancer, and dementia start with the failure to resolve inflammation so by getting adequate levels of omega-3s early on you can help to promote a lifetime of wellness. {{cta('70a4b644-a93c-4f8b-83ec-5be1500ed236')}}
What is Cellular Inflammation?
People (including virtually all physicians) are constantly confused what cellular inflammation is. So I decided to take the opportunity to explain the concept in more detail. There are two types of inflammation. The first type is classical inflammation, which generates the inflammatory response we associate with pain such as, heat, redness, swelling, pain, and eventually loss of organ function. The other type is cellular inflammation, which is below the perception of pain. Cellular inflammation is the initiating cause of chronic disease because it disrupts hormonal signaling networks throughout the body. Definition of Cellular Inflammation The definition of cellular inflammation is increased activity of the gene transcription factor know as Nuclear Factor-kappaB (NF-κB). This is the gene transcription factor found in every cell, and it activates the inflammatory response of the innate immune system. Although the innate immune system is the most primitive part of our immune response, it has been resistant to study without recent breakthroughs in molecular biology. In fact, the 2011 Nobel Prize in Medicine was awarded for the earliest studies on the innate immune system and its implications in the development of chronic disease. There are several extracellular events through which NF-κB can be activated by distinct mechanisms. These include microbial invasion recognized by toll-like receptors (TLR), generation of reactive oxygen species (ROS), cellular generation of inflammatory eicosanoids, and interaction with inflammatory cytokines via defined cell surface receptors. We also know that several of these initiating events are modulated by dietary factors. This also means that appropriate use of the diet can either turn on or turn off the activation of NF-κB. This new knowledge is the foundation of anti-inflammatory nutrition (1-3). Understanding Cellular Inflammation Although the innate immune system is exceptionally complex, it can be illustrated in a relatively simple diagram as shown below in Figure 1. Figure 1. Simplified View of the Innate Immune System Essential fatty acids are the most powerful modulators of NF-κB. In particular, the omega-6 fatty acid arachidonic acid (AA) activates NF-κB, whereas the omega-3 fatty acid eicosapentaenoic acid (EPA) does not (4). Recent work suggests that a subgroup of eicosanoids known as leukotrienes that are derived from AA may play a significant factor in NF-κB activation (5,6) Extracellular inflammatory cytokines can also activate NF-κB by their interaction with specific receptors on the cell surface. The primary cytokine that activates NF-κB is tumor necrosis factor (TNF) (7). Toll-like receptors (TLR) are another starting point for the activation of NF-κB. In particular, TLR-4 is sensitive to dietary saturated fatty acids (8). The binding of saturated fatty acids to TLR-4 can be inhibited by omega-3 fatty acids such as EPA. Finally ROS either induced by ionizing radiation or by excess free radical formation are additional activators of NF-κB (9). Anti-inflammatory Nutrition To Inhibit Cellular Inflammation Anti-inflammatory nutrition is based on the ability of certain nutrients to reduce the activation of NF-κB. The most effective way to lower the activation of NF-κB is to reduce the levels of AA in the target cell membrane thus reducing the formation of leukotrienes that can activate NF-κB. Having the patient follow an anti-inflammatory diet, such as the Zone Diet coupled with the simultaneous lowering omega-6 fatty acid intake are the primary dietary strategies to accomplish this goal (1-3). Another effective dietary approach (and often easier for the patient to comply with) is the dietary supplementation with adequate levels of high-dose fish oil rich in omega-3 fatty acids, such as EPA and DHA. These omega-3 fatty acids taken at high enough levels will lower AA levels and increase EPA levels. This change of the AA/EPA ratio in the cell membrane will reduce the likelihood of the formation of inflammatory leukotrienes that can activate NF-κB. This is because leukotrienes derived from AA are pro-inflammatory, whereas those from EPA are non-inflammatory. The increased intake of omega-3 fatty acids is also a dietary approach that can activate the anti-inflammatory gene transcription factor PPAR-γ (10-12), decrease the formation of ROS (13) and decrease the binding of saturated fatty acids to TLR-4 (14). This illustrates the multi-functional roles that omega-3 fatty acids have in controlling cellular inflammation. A third dietary approach is the adequate intake of dietary polyphenols. These are compounds that give fruits and vegetables their color. At high levels they are powerful anti-oxidants to reduce the generation of ROS (15). They can also inhibit the activation of NF-κB (16). Finally, the least effective dietary strategy (but still useful) is the reduction of dietary saturated fat intake. This is because saturated fatty acids will cause the activation of the TLR-4 receptor in the cell membrane (8,14). Obviously, the greater the number of these dietary strategies implemented by the patient, the greater the overall effect on reducing cellular inflammation. Clinical Measurement of Cellular Inflammation Since cellular inflammation is confined to the cell itself, there are few blood markers that can be used to directly measure the levels of systemic cellular inflammation in a cell. However, the AA/EPA ratio in the blood appears to be a precise and reproducible marker of the levels of the same ratio of these essential fatty acids in the cell membrane. As described above, the leukotrienes derived from AA are powerful modulators of NF-κB. Thus a reduction in the AA/EPA ratio in the target cell membrane will lead to a reduced activation of NF-κB by decreased formation of inflammatory leukotrienes. The cell membrane is constantly being supplied by AA and EPA from the blood. Therefore the AA/EPA ratio in the blood becomes an excellent marker of the same ratio in the cell membrane (17). Currently the best and most reproducible marker of cellular inflammation is the AA/EPA ratio in the blood as it represents an upstream control point for the control of NF-κB activation. The most commonly used diagnostic marker of inflammation is C-reactive protein (CRP). Unlike the AA/EPA ratio, CRP is a very distant downstream marker of past NF-κB activation. This is because one of inflammatory mediators expressed in the target cell is IL-6. It must eventually reach a high enough level in the blood to eventually interact with the liver or the fat cells to produce CRP. This makes CRP a more long-lived marker in the blood stream compared to the primary inflammatory gene products (IL-1, IL-6, TNF, and COX-2) released after the activation of NF-κB. As a consequence, CRP is easier to measure than the most immediate inflammatory products generated by NF-κB activation. However, easier doesn’t necessarily translate into better. In fact, an increase AA/EPA ratio in the target cell membrane often precedes any increase of C-reactive protein by several years. An elevated AA/EPA ratio indicates that NF-κB is at the tipping point and the cell is primed for increased genetic expression of a wide variety of inflammatory mediators. The measurement of CRP indicates that NF-κB has been activated for a considerable period of time and that cellular inflammation is now causing systemic damage. In Summary I believe the future of medicine lies in the control of cellular inflammation. This is most effectively accomplished by the constant application of anti-inflammatory nutrition. The success of such dietary interventions can be measured clinically by the reduction of the AA/EPA ratio in the blood. {{cta('4f5c5df9-024e-4218-ab5e-8490f8243f6f')}} References: Sears B. The Anti-Inflammation Zone. Regan Books. New York, NY (2005). Sears B. Toxic Fat. Thomas Nelson. Nashville, TN (2008). Sears B and Riccordi C. “Anti-inflammatory nutrition as a pharmacological approach to treat obesity.” J Obesity doi:10.1155/2011/431985 (2011). Camandola S, Leonarduzzi G,Musso T, Varesio L, Carini R, Scavazza A, Chiarpotto E, Baeuerle PA, and Poli G. “Nuclear factor kB is activated by arachidonic acid but not by eicosapentaenoic acid.” Biochem Biophys Res Commun 229:643-647 (1996). Sears DD, Miles PD, Chapman J, Ofrecio JM, Almazan F, Thapar D, and Miller YI. “12/15-lipoxygenase is required for the early onset of high fat diet-induced adipose tissue inflammation and insulin resistance in mice.” PLoS One 4:e7250 (2009). Chakrabarti SK, Cole BK, Wen Y, Keller SR, and Nadler JL. “12/15-lipoxygenase products induce inflammation and impair insulin signaling in 3T3-L1 adipocytes.” Obesity 17:1657-1663 (2009). Min JK, Kim YM, Kim SW, Kwon MC, Kong YY, Hwang IK, Won MH, Rho J, and Kwon YG. “TNF-related activation-induced cytokine enhances leukocyte adhesiveness: induction of ICAM-1 and VCAM-1 via TNF receptor-associated factor and protein kinase C-dependent NF-kappaB activation in endothelial cells.” J Immunol 175: 531-540 (2005). Kim JJ and Sears DD. “TLR4 and Insulin Resistance.” Gastroenterol Res Pract doi:10./2010/212563 (2010). Bubici C, Papa S, Dean K, and Franzoso G. “Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance.” Oncogene 25: 6731-6748 (2006). Li H, Ruan XZ, Powis SH, Fernando R, Mon WY, Wheeler DC, Moorhead JF, and Varghese Z. “EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: Evidence for a PPAR-gamma-dependent mechanism.” Kidney Int 67: 867-874 (2005). Kawashima A, Harada T, Imada K, Yano T, and Mizuguchi K. “Eicosapentaenoic acid inhibits interleukin-6 production in interleukin-1beta-stimulated C6 glioma cells through peroxisome proliferator-activated receptor-gamma.” Prostaglandins LeukotEssent Fatty Acids 79: 59-65 (2008). Chambrier C, Bastard JP, Rieusset J, Chevillotte E, Bonnefont-Rousselot D, Therond P, Hainque B, Riou JP, Laville M, and Vidal H. “Eicosapentaenoic acid induces mRNA expression of peroxisome proliferator-activated receptor gamma.” Obes Res 10: 518-525 (2002). Mas E, Woodman RJ, Burke V, Puddey IB, Beilin LJ, Durand T, and Mori TA. “The omega-3 fatty acids EPA and DHA decrease plasma F(2)-isoprostanes.” Free Radic Res 44: 983-990 (2010). Lee JY, Plakidas A, Lee WH, Heikkinen A, Chanmugam P, Bray G, and Hwang DH. “Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids.” J Lipid Res 44: 479-486 (2003). Crispo JA, Ansell DR, Piche M, Eibl JK, Khaper N, Ross GM, and Tai TC. “Protective effects of polyphenolic compounds on oxidative stress-induced cytotoxicity in PC12 cells.” Can J Physiol Pharmacol 88: 429-438 (2010). Romier B, Van De Walle J, During A, Larondelle Y, and Schneider YJ. “Modulation of signaling nuclear factor-kappaB activation pathway by polyphenols in human intestinal Caco-2 cells.” Br J Nutr 100: 542-551 (2008). Yee LD, Lester JL, Cole RM, Richardson JR, Hsu JC, Li Y, Lehman A, Belury MA, and Clinton SK. “Omega-3 fatty acid supplements in women at high risk of breast cancer have dose-dependent effects on breast adipose tissue fatty acid composition.” Am J Clin Nutr 91: 1185-1194 (2010).
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