Fork U with Dr. Terry Simpson

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Fructose: Evil or Misunderstood? Nov 10, 2021

Show notes

Ever since the YouTube video of Dr. Lustig and the evils of fructose went viral in 2010, many have advocated that fructose is the single most common cause of obesity in the United States.

The video had metabolic pathways that had the hypothesis that most fructose either becomes fat in the liver, or that it might go down a pathway to cause joint issues, leaky gut, and inflammation causing obesity.

Here are the two chemical structures of glucose, also known as the "good sugar" and fructose, or the bad sugar. I cannot help but thinking of the good witch and the bad witch on the Wizard of Oz.

Dr. Lustig's hypothesis was based on studies done in mice and rats. In those studies, published two years before the viral video, found that high fructose diets in mice lead to increased "gut leak" and led to liver damage (1). This was even confirmed with a small study of 8 men (2) who had their complex carbohydrates replaced by fructose and fed normal caloric diets - meaning, these eight men had increased liver fat, more de novo fat formation (de novo lipogenesis) .

This all makes that logical sense since sugar-sweetened beverages are associated with chronic inflammation and these days everything to do with chronic inflammation increases the risk of obesity, diabetes, heart disease, and aging.

Then came a double-blinded, randomized, crossover study where a group of people were fed a standard diet but drank 25% of their calories as either fructose (the evil sugar), or glucose (the good one) or a high fructose corn syrup sweetened beverage. Oddly, there was no difference in any of those groups with regard to markers of inflammation, intestinal permeability, or inflammation in the fat tissue.

To quote from the study: "Excessive amounts of fructose, HFCS, and glucose from SSBs consumed over 8 d did not differentially affect low-grade chronic systemic inflammation in normal-weight to obese adults." SSB = sugar sweetened beverages.

There have been a number of human trials looking at sugar-sweetened beverages and inflammation, and the results are not consistent. Even finding that people who drink large amounts of either glucose of fructose didn't find changes in inflammation or visceral fat.

Mice are not men, and the link between gut permeability, leading to systemic and chronic inflammation, occurs in mice, but not men. And while in mice fructose can lead to inflammation and liver issues, this doesn't happen in human beings. (4)

The key may not be fructose itself, but increased caloric intake. If you eat more, you will increase in weight, but it is not fructose alone. It is, in fact, high caloric intake combined with sugars. Meaning, that great tasting snack with the high levels of sugars and fats act in concert with the increased calories consumed to give you that portly look.

To be fair, all of the studies were short term, less than a couple of weeks. Fructose, over the long term, may still be a bad actor.

What about fruit? It is exceedingly difficult to eat enough whole fruits to make this a problem. To eat the excess amount in some of these studies you would have to eat several pounds of apples, and most people simply cannot do that in a day. And whole fruit consumption, as a part of the Mediterranean diet reduces the burden of cardiovascular disease, diabetes, and even erectile dysfunction.(5)

In fact less than 10% of most Western dieters have adequate levels of fruit (6) leading to a serious threat to human health. Maybe a couple of apples a day will keep the doctor away.

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Fork U is part of the Your Doctors Orders network of podcasts and is hosted by noted physician and surgeon Dr. Terry Simpson.

Follow Dr. Terry Simpson on TikTok for bite-sized content on healthy eating
Visit TerrySimpson.com for additional details on Dr. Simpson
Follow @DrTerrySimpson on Twitter for skepticism, travel, and much more.

Fork U is produced by Simpler Media and is recorded in the studios of ProducerGirl Productions.

REFERENCES:

(1) Bergheim I, Weber S, Vos M, Krämer S, Volynets V, Kaserouni S, McClain CJ, Bischoff SC. Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin. J Hepatol. 2008 Jun;48(6):983-92. doi: 10.1016/j.jhep.2008.01.035. Epub 2008 Mar 14. PMID: 18395289.

(2) Schwarz JM, Noworolski SM, Wen MJ, Dyachenko A, Prior JL, Weinberg ME, Herraiz LA, Tai VW, Bergeron N, Bersot TP, Rao MN, Schambelan M, Mulligan K. Effect of a High-Fructose Weight-Maintaining Diet on Lipogenesis and Liver Fat. J Clin Endocrinol Metab. 2015 Jun;100(6):2434-42. doi: 10.1210/jc.2014-3678. Epub 2015 Mar 31. PMID: 25825943; PMCID: PMC4454806.

(3) Kuzma JN, Cromer G, Hagman DK, Breymeyer KL, Roth CL, Foster-Schubert KE, Holte SE, Weigle DS, Kratz M. No differential effect of beverages sweetened with fructose, high-fructose corn syrup, or glucose on systemic or adipose tissue inflammation in normal-weight to obese adults: a randomized controlled trial. Am J Clin Nutr. 2016 Aug;104(2):306-14. doi: 10.3945/ajcn.115.129650. Epub 2016 Jun 29. PMID: 27357093; PMCID: PMC4962158.

(4) Chung M, Ma J, Patel K, Berger S, Lau J, Lichtenstein AH. Fructose, high-fructose corn syrup, sucrose, and nonalcoholic fatty liver disease or indexes of liver health: a systematic review and meta-analysis. Am J Clin Nutr. 2014 Sep;100(3):833-49. doi: 10.3945/ajcn.114.086314. Epub 2014 Aug 6. PMID: 25099546; PMCID: PMC4135494.

(5) Widmer RJ, Flammer AJ, Lerman LO, Lerman A. The Mediterranean diet, its components, and cardiovascular disease. Am J Med. 2015 Mar;128(3):229-38. doi: 10.1016/j.amjmed.2014.10.014. Epub 2014 Oct 15. PMID: 25447615; PMCID: PMC4339461.

(6) Dreher ML. Whole Fruits and Fruit Fiber Emerging Health Effects. Nutrients. 2018 Nov 28;10(12):1833. doi: 10.3390/nu10121833. PMID: 30487459; PMCID: PMC6315720.

Red Meat: Is it good or bad? The answer is... sometimes Oct 26, 2021

Show notes

On my tiktok channel (@drterrysimpson or terrysimpson309) putting up a review of red meat the comments are reflective of the polarization that makes politics look like gentle disagreements.Nutrition is nuanced - meaning, it is rare that something is good or bad for us, except for Death Cap Mushrooms, they will kill you, although I hear they are delicious. The same is true for red meat. What we have are rarely the types of nutrition studies where we feed people precise amounts of food and see the results (the DASH diet studies were great with this -ref 1 ). Instead we rely on what people tell us, which can be accurate, or not - and we look at markers for disease instead of the disease itself (looking at end points of heart disease we look at LDL, cholesterol, C-reactive protein, and rather non-specific markers.Red Meat and Glycemic Control and InflammationIn this study (ref 2) they examined the premise that red meat's has an effect on inflammatory markers and glycemic control. So the study was a meta analysis of randomized control of glycemic control and inflammatory markers.Adults that were studied were given various quantities of red meats and then checked for glycemic control and inflammation. The end result "Total red meat consumption, for up to 16 weeks, does not affect changes in biomarkers of glycemic control or inflammation for adults free of, but at risk for, cardiometabolic disease. "Does this put this to bed - not really, but the proposed ill effect of red meat is not something that is seen in these studies. Here are the markers they studied: glucose, insulin levels, HOMA-R, Hemoglobin A1c, C-reactive protein, IL-6, and TNF-alpha.This was a group of studies that went to about 16 weeks (four months) so any longer term issues with red or even red processed meats, were not seen. But there were clearly no indication found in these studies.What about other markers for heart disease?So the next question is the effect of red meat on lipids, lipoproteins and blood pressure(ref 3)? It turned out that increasing red meat did not affect those variables for heart disease.What if you check not just red meat, but "red meat with diets that replaced red meat with a variety of foods. We stratified comparison diets into high-quality plant protein sources (legumes, soy, nuts); chicken/poultry/fish; fish only; poultry only; mixed animal protein sources (including dairy); carbohydrates (low-quality refined grains and simple sugars, such as white bread, pasta, rice, cookies/biscuits); or usual diet. We performed random-effects meta-analyses comparing differences in changes of blood lipids, apolipoproteins, and blood pressure for all studies combined and stratified by specific comparison diets."- from ref 4. They found that changing red meat for plant protein had a minimal effect, and yet other studies (ref 2) found that plant protein had no significant difference at all.Those short term studies, which are clear changes with specific amounts over a short period of time, appear to contrast with the studies of various groups where they look at the risk of type 2 diabetes and red meat consumption. Take reference 5, where they looked at the increase of diabetes in different groups based on self-reporting of red meat intake. These studies are not as powerful as the controlled trials above, and they are confounded by other variables - people who eat more red meat have higher caloric intake and more obesity, they also tend to drink more and to smoke more. It is not easy to isolate, statistically, those variables out and this is always the issue with large cohort studies.Take the many studies of the Seventh Day Adventist group, who are considered America's Blue Zone in Loma Linda, California. They don't eat meat, they live longer -- but there is more, that group tends to exercise more, they do not smoke, they do not drink, and they have a strong sense of community. When studied (reference 6) it appears to have an increased in all cause mortality with an increase in red meat and processed meat. But again, a cohort study where it is difficult to refine the variables is not as strong as a study where you feed people precise amounts and look for surrogate markers of disease.The other issue with following cohort groups is what else they consume. Red meat eaters who increase vegetables have lower long term risk of colo-rectal cancer or as we say - the risk of colon cancer is mitigated by increased vegetable and fibrous foods. While looking at cohorts of meat eaters they tend not to eat much in the way of this food, in some studies they can account for this, in some studies they cannot and it becomes all the more confusing (ref 7).When looking at red meat and heart disease, researchers have wondered why poultry doesn't seem to cause an increase in heart disease as red meat. One thought is that it is the increased iron with red meat, or the heme protein. While this has never been proven, and there are no good animal models for this, one unique theory is the reason people who exercise more have less issue with red meat is not only being in shape, but that exercise causes a faster turnover of blood cells allowing less build up of iron and thus less issues with heart disease (reference 8). I know, it is a long way around for a hypothesis that seems interesting and novel but doesn't quite make it out of any laboratory model. But from so many studies in medicine and science, while we can make a perfectly good logical argument, biology often is more elegant than our sense of logic.Another novel idea is that red meat is as a source of glycation end products which can lead to inflammation. So stick with me here - " Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars. AGEs are prevalent in the diabetic vasculature and contribute to the development of atherosclerosis." - from ref 9. These are thought to be a marker, or even one of the terminal pathways for atherosclerosis and perhaps even neuropathy from diabetes. And while it again, makes a logical argument to decrease red meat and inflammation, the studies do not show that a decrease in red meat will actually do this. Again, logic doesn't make biology.Is it Good or is it Bad?Isn't that what we all want to know? When the Annals of Internal Medicine published five papers looking at red meat it caused quite a stir, because many were thinking red meat was bad.The first one (ref 10) looked at 61 articles with 55 cohorts and they found: "Low-certainty evidence was found that a reduction in unprocessed red meat intake of 3 servings per week is associated with a very small reduction in risk for cardiovascular mortality, stroke, myocardial infarction (MI), and type 2 diabetes. Likewise, low-certainty evidence was found that a reduction in processed meat intake of 3 servings per week is associated with a very small decrease in risk for all-cause mortality, cardiovascular mortality, stroke, MI, and type 2 diabetes." So giving up a bit of meat doesn't have a lot of evidence that it makes a large difference.What about Cancer?No one wants cancer, so what about red meat and cancer? Well this brings us to reference 11. To quote: "Of 118 articles (56 cohorts) with more than 6 million participants, 73 articles were eligible for the dose-response meta-analyses, 30 addressed cancer mortality, and 80 reported cancer incidence. Low-certainty evidence suggested that an intake reduction of 3 servings of unprocessed meat per week was associated with a very small reduction in overall cancer mortality over a lifetime. Evidence of low to very low certainty suggested that each intake reduction of 3 servings of processed meat per week was associated with very small decreases in overall cancer mortality over a lifetime; prostate cancer mortality; and incidence of esophageal, colorectal, and breast cancer." So we think, with a lot of uncertainty, that reducing intake of meat or processed meat may have a small decrease in mortality from cancer. Is it worth that decrease in risk - we are not certain.Are you willing to give up red meat?I mean, it is delicious, but let's look at the data in reference 12. If we cannot say for certain that meat will cause you a problem then most people are not willing to give it up - to quote: "Low-certainty evidence suggests that omnivores are attached to meat and are unwilling to change this behavior when faced with potentially undesirable health effects." So for all the preaching that vegans might do to give up meat, it turns out that meat lovers are not going to change behavior especially given the evidence is pretty weak.Cancer and Heart Disease and DeathThe final of the great five papers was looking at the effect of lower vs higher intake of meat have little or no impact on mortality from heart disease or cancer. To quote "Of 12 eligible trials, a single trial enrolling 48 835 women provided the most credible, though still low-certainty, evidence that diets lower in red meat may have little or no effect on all-cause mortality (hazard ratio [HR], 0.99 [95% CI, 0.95 to 1.03]), cardiovascular mortality (HR, 0.98 [CI, 0.91 to 1.06]), and cardiovascular disease (HR, 0.99 [CI, 0.94 to 1.05]). That trial also provided low- to very-low-certainty evidence that diets lower in red meat may have little or no effect on total cancer mortality (HR, 0.95 [CI, 0.89 to 1.01]) and the incidence of cancer, including colorectal cancer (HR, 1.04 [CI, 0.90 to 1.20]) and breast cancer (HR, 0.97 [0.90 to 1.04])." This is reference 13.So can I enjoy the steak?In conclusion you can. The difficulty with red meat is that everyone looks at cigarettes and thinks we have that kind of association, but we don't. You can cherry pick data, but when you look at all the data it is small. Look at the relative risk of eating red meat - it doesn't get to 2, where as the relative risk of cancer from smoking is 20 - and this is a log scale.This is not the end, we still need real studies with more variables that are able to be controlled in a tight environment, or statistically removed.If you are obese, don't exercise, and don't otherwise eat well it is differentOne thing is clear from a number of studies - if you are overweight, if you don't exercise, if you don't eat a lot of vegetables, legumes, whole grains, and fruits, then eating red meat is not the best choice. Not only is it filled with saturated fat and calorie dense, so it will increase all risk factors - the other variables in your life probably need to change, as they all have their own mortality and morbidity associated with them.Hey - hit me up on tiktok for comments - join the fray - and listen to the podcast-----Fork U is part of the Your Doctors Orders network of podcasts and is hosted by noted physician and surgeon Dr. Terry Simpson.Follow Dr. Terry Simpson on TikTok for bite-sized content on healthy eatingVisit TerrySimpson.com for additional details on Dr. SimpsonFollow @DrTerrySimpson on Twitter for skepticism, travel, and much more.Fork U is produced by Simpler Media and is recorded in the studios of ProducerGirl Productions. REFERENCES(1). Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER 3rd, Simons-Morton DG, Karanja N, Lin PH; DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001 Jan 4;344(1):3-10. doi: 10.1056/NEJM200101043440101. PMID: 11136953.(2). O'Connor LE, Kim JE, Clark CM, Zhu W, Campbell WW. Effects of Total Red Meat Intake on Glycemic Control and Inflammatory Biomarkers: A Meta-Analysis of Randomized Controlled Trials. Adv Nutr. 2021 Feb 1;12(1):115-127. doi: 10.1093/advances/nmaa096. PMID: 32910818; PMCID: PMC7850054.(3). O'Connor LE, Kim JE, Campbell WW. Total red meat intake of ≥0.5 servings/d does not negatively influence cardiovascular disease risk factors: a systemically searched meta-analysis of randomized controlled trials. Am J Clin Nutr. 2017 Jan;105(1):57-69. doi: 10.3945/ajcn.116.142521. Epub 2016 Nov 23. PMID: 27881394; PMCID: PMC5183733.(4). Guasch-Ferré M, Satija A, Blondin SA, Janiszewski M, Emlen E, O'Connor LE, Campbell WW, Hu FB, Willett WC, Stampfer MJ. Meta-Analysis of Randomized Controlled Trials of Red Meat Consumption in Comparison With Various Comparison Diets on Cardiovascular Risk Factors. Circulation. 2019 Apr 9;139(15):1828-1845. doi: 10.1161/CIRCULATIONAHA.118.035225. PMID: 30958719.(5). Pan A, Sun Q, Bernstein AM, Manson JE, Willett WC, Hu FB. Changes in red meat consumption and subsequent risk of type 2 diabetes mellitus: three cohorts of US men and women. JAMA Intern Med. 2013 Jul 22;173(14):1328-35. doi: 10.1001/jamainternmed.2013.6633. PMID: 23779232; PMCID: PMC3847817.(6). Alshahrani SM, Fraser GE, Sabaté J, Knutsen R, Shavlik D, Mashchak A, Lloren JI, Orlich MJ. Red and Processed Meat and Mortality in a Low Meat Intake Population. Nutrients. 2019 Mar 14;11(3):622. doi: 10.3390/nu11030622. PMID: 30875776; PMCID: PMC6470727.(7) Turner ND, Lloyd SK. Association between red meat consumption and colon cancer: A systematic review of experimental results. Exp Biol Med (Maywood). 2017 Apr;242(8):813-839. doi: 10.1177/1535370217693117. Epub 2017 Jan 1. PMID: 28205448; PMCID: PMC5407540.(8). Qi L, van Dam RM, Rexrode K, Hu FB. Heme iron from diet as a risk factor for coronary heart disease in women with type 2 diabetes. Diabetes Care. 2007 Jan;30(1):101-6. doi: 10.2337/dc06-1686. PMID: 17192341.(9). Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006 Aug 8;114(6):597-605. doi: 10.1161/CIRCULATIONAHA.106.621854. PMID: 16894049.(10). Zeraatkar D, Han MA, Guyatt GH, Vernooij RWM, El Dib R, Cheung K, Milio K, Zworth M, Bartoszko JJ, Valli C, Rabassa M, Lee Y, Zajac J, Prokop-Dorner A, Lo C, Bala MM, Alonso-Coello P, Hanna SE, Johnston BC. Red and Processed Meat Consumption and Risk for All-Cause Mortality and Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Cohort Studies. Ann Intern Med. 2019 Nov 19;171(10):703-710. doi: 10.7326/M19-0655. Epub 2019 Oct 1. PMID: 31569213.(11). Han MA, Zeraatkar D, Guyatt GH, Vernooij RWM, El Dib R, Zhang Y, Algarni A, Leung G, Storman D, Valli C, Rabassa M, Rehman N, Parvizian MK, Zworth M, Bartoszko JJ, Lopes LC, Sit D, Bala MM, Alonso-Coello P, Johnston BC. Reduction of Red and Processed Meat Intake and Cancer Mortality and Incidence: A Systematic Review and Meta-analysis of Cohort Studies. Ann Intern Med. 2019 Nov 19;171(10):711-720. doi: 10.7326/M19-0699. Epub 2019 Oct 1. PMID: 31569214.(12). Valli C, Rabassa M, Johnston BC, Kuijpers R, Prokop-Dorner A, Zajac J, Storman D, Storman M, Bala MM, Solà I, Zeraatkar D, Han MA, Vernooij RWM, Guyatt GH, Alonso-Coello P; NutriRECS Working Group. Health-Related Values and Preferences Regarding Meat Consumption: A Mixed-Methods Systematic Review. Ann Intern Med. 2019 Nov 19;171(10):742-755. doi: 10.7326/M19-1326. Epub 2019 Oct 1. PMID: 31569219.(13). Zeraatkar D, Johnston BC, Bartoszko J, Cheung K, Bala MM, Valli C, Rabassa M, Sit D, Milio K, Sadeghirad B, Agarwal A, Zea AM, Lee Y, Han MA, Vernooij RWM, Alonso-Coello P, Guyatt GH, El Dib R. Effect of Lower Versus Higher Red Meat Intake on Cardiometabolic and Cancer Outcomes: A Systematic Review of Randomized Trials. Ann Intern Med. 2019 Nov 19;171(10):721-731. doi: 10.7326/M19-0622. Epub 2019 Oct 1. PMID: 31569236.

Full show notes at the publisher

The Carnivore Diet and Myths Oct 10, 2021

Show notes

The Carnivore diet is the most extreme of the low-carbohydrate diets, with its expressed point that humans did great on a diet of flesh and evolved to eat a diet high in fats.

While we cannot make up what people ate in the past, we can see about the diet of the Yupik’s of Alaska. These people have been studied extensively by the Center for Alaska Native Health Research (CANHR) at the University of Alaska in Fairbanks who partnered with Genetics of Coronary Artery Disease in Alaska Native people.

First the CANHR found that Alaska Natives who ate processed meats (hot dogs, lunch meat, fried chicken) had higher triglycerides. Those Yupik’s who consumed lots of omega-3 fatty acids and ate lots of meats with saturated fats developed coronary artery disease. As much as we like to get our omega-3 fatty acids from the sources, and few in the world eat as many as the Yupik’s, that cannot protect you from coronary artery disease in the presence of the over-consumption of saturated and trans fatty acids. It further showed that, at least for the Yupik’s, consuming processed meats, and meats high in saturated fats like beef, pork, lamb and chicken with skin was not healthy for the Alaska Natives.

The Carnivore diet excludes greens and berries, however sea greens and berries are a large part of the traditional Yupik diet. The diet that they have is high in marine mammals, fish, game animals, greens and berries that provide high levels of fat soluble vitamins (A,D,E, and K) as well as iron.

The Biotruth of the Carnivore Diet:

A biotruth is a logical fallacy, usually found to be a misunderstanding of evolution. In this case the idea that early human ancestors were meat eaters and that the adaptation of cultivation of crops led to chronic disease.

When CT scans were looked at from 137 mummified remains from four geographical regions, ancient Egypt, Peru, the Pueblo, and Unangan from the Aleutian Islands were examined they found atherosclerosis in all of them.

“Interpretation: Atherosclerosis was common in four preindustrial populations including preagricultural hunter-gatherers. Although commonly assumed to be a modern disease, the presence of atherosclerosis in premodern human beings raises the possibility of a more basic predisposition to the disease.”

It should be noted that those were diverse diets from those who ate primarily marine mammals and fish to those whose diet was composed primarily of vegetation with little meat.

The Myths of LDL

The low carbohydrate community propose that LDL isn’t an issue with heart disease. This flies in the face of the recent article in JAMA looking at 34 clinical trials and finding that lowering LDL-C not only decreased the risk of heart disease, but all causes of mortality. While the low-carb crowd likes to point out how sugar indeed has a role in development of heart disease, they quietly forget to point out that diets rich in meats are overwhelmingly an issue.

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Fork U is part of the Your Doctors Orders network of podcasts and is hosted by noted physician and surgeon Dr. Terry Simpson.

Follow Dr. Terry Simpson on TikTok for bite-sized content on healthy eating
Visit TerrySimpson.com for additional details on Dr. Simpson
Follow @DrTerrySimpson on Twitter for skepticism, travel, and much more.

Fork U is produced by Simpler Media and is recorded in the studios of ProducerGirl Productions.

-----

REFERENCES

Brand-Miller JC, Griffin HJ, Colagiuri S. The carnivore connection hypothesis: revisited. J Obes. 2012;2012:258624. doi: 10.1155/2012/258624. Epub 2011 Dec 22. PMID: 22235369; PMCID: PMC3253466.

Bersamin A, Luick BR, King IB, Stern JS, Zidenberg-Cherr S. Westernizing diets influence fat intake, red blood cell fatty acid composition, and health in remote Alaskan Native communities in the center for Alaska Native health study. J Am Diet Assoc. 2008 Feb;108(2):266-73. doi: 10.1016/j.jada.2007.10.046. PMID: 18237575; PMCID: PMC6542563.

Ryman TK, Boyer BB, Hopkins S, Philip J, Beresford SA, Thompson B, Heagerty PJ, Pomeroy JJ, Thummel KE, Austin MA. Associations between diet and cardiometabolic risk among Yup'ik Alaska Native people using food frequency questionnaire dietary patterns. Nutr Metab Cardiovasc Dis. 2015 Dec;25(12):1140-5. doi: 10.1016/j.numecd.2015.08.003. Epub 2015 Aug 21. PMID: 26607703; PMCID: PMC4684467.

Thompson RC, Allam AH, Lombardi GP, Wann LS, Sutherland ML, Sutherland JD, Soliman MA, Frohlich B, Mininberg DT, Monge JM, Vallodolid CM, Cox SL, Abd el-Maksoud G, Badr I, Miyamoto MI, el-Halim Nur el-Din A, Narula J, Finch CE, Thomas GS. Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations. Lancet. 2013 Apr 6;381(9873):1211-22. doi: 10.1016/S0140-6736(13)60598-X. Epub 2013 Mar 12. PMID: 23489753.

Bersamin A, Zidenberg-Cherr S, Stern JS, Luick BR. Nutrient intakes are associated with adherence to a traditional diet among Yup'ik Eskimos living in remote Alaska Native communities: the CANHR Study. Int J Circumpolar Health. 2007 Feb;66(1):62-70. doi: 10.3402/ijch.v66i1.18228. PMID: 17451135.

Ebbesson SO, Risica PM, Ebbesson LO, Kennish JM. Eskimos have CHD despite high consumption of omega-3 fatty acids: the Alaska Siberia project. Int J Circumpolar Health. 2005 Sep;64(4):387-95. doi: 10.3402/ijch.v64i4.18015. PMID: 16277122.

Bjerregaard P, Young TK, Hegele RA. Low incidence of cardiovascular disease among the Inuit--what is the evidence? Atherosclerosis. 2003 Feb;166(2):351-7. doi: 10.1016/s0021-9150(02)00364-7. PMID: 12535749.

Navarese, E. P., Robinson, J. G., Kowalewski, M., Kolodziejczak, M., Andreotti, F., Bliden, K., Tantry, U., Kubica, J., Raggi, P., & Gurbel, P. A. (2018). Association Between Baseline LDL-C Level and Total and Cardiovascular Mortality After LDL-C Lowering: A Systematic Review and Meta-analysis. JAMA, 319(15), 1566–1579. https://doi.org/10.1001/jama.2018.2525

Fish Oil and Atrial Fibrillation Sep 25, 2021

Show notes

Fish oil is the bomb - Greenland Yupik and the rise of fish oil

Fish oil first became a "hot topic" when a 1980 publication showed that Yupik in Greenland had a lower incidence of cardiovascular disease.

Their paper concluded, "The rarity of ischemic heart disease in Greenland Eskimos may partly be explained by the antithrombotic effect of the long-chained polyunsaturated fatty acids, especially eicosapentaenoic acid prevalent in diets rich in marine oils." (Bang HO, Dyerberg J, Sinclair HM. The composition of the Eskimo food in north western Greenland. Am J Clin Nutr. 1980 Dec;33(12):2657-61. doi: 10.1093/ajcn/33.12.2657. PMID: 7435433).

This led to more scientific bodies looking at the evidence for fish oil, and ultimately omega 3 fatty acids, and if it did reduce the incidence of cardiovascular disease. And even 22 years after the publication of that study, the American Heart Association put out a statement that fish oil was protective against cardiovascular disease. (Kris-Etherton PM, Harris WS, Appel LJ; American Heart Association. Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002 Nov 19;106(21):2747-57. doi: 10.1161/01.cir.0000038493.65177.94. Erratum in: Circulation. 2003 Jan 28;107(3):512. PMID: 12438303)

The other predictable tract this led on was the inevitable marketing of fish oils in the supplement industry trying to sell fish oil capsules, from whatever source, as a "must take" to prevent the number one killer in the United States. As with most supplements, being unregulated, they would make claims that their oil was better than others - because it came from krill, or it was vegan-based, or from cod, or pick something that sounds like it can be marketed. Some would claim their fish oil was more pure omega 3 fatty acids. Radio and television spots were secured, and when it was confirmed that the "good cholesterol" or HDL was indeed raised by omega 3 fatty acids it raised their game and intensity of marketing.

Back in the world of science, testing continued and the results that came back didn't match the conclusions.

Some papers would conclude that fish oil didn't produce a significant decrease in first time cardiac events but might help prevent secondary cardiac events (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, Shirato K; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomized open-label, blinded endpoint analysis. Lancet. 2007 Mar 31;369(9567):1090-8. doi: 10.1016/S0140-6736(07)60527-3. Erratum in: Lancet. 2007 Jul 21;370(9583):220. PMID: 17398308).

In 2004 the Cocharane database looked at 48 randomized controlled trials and concluded that taking fish oils did not reduce mortality from cardiovascular disease. It also concluded that it didn't matter where the fish oil came from, fish or plant sources, or other sources. This, as you might imagine, throws a monkey wrench into the statement by the American Heart Association that fish oils were good for you, especially coming two years later.

Marketing moves faster than medicine, so while doctors and scientists were working to find out why there were inconsistent results, the marketing of fish oils continued to expand. Given that there was no regulation in the supplement industry, they continued to market the "benefits" of their product. By 2020 the sales of over-the-counter fish oil products became to a SIX BILLION dollar industry, (https://www.grandviewresearch.com/industry-analysis/omega-3-supplement-market).

Scientists worked at looking at the different components of dietary, or essential fatty acids. Because the literature was confusing, and the American Heart Association had a bit of salmon egg on their face, they decided to get their best and brightest to review the data and come to a conclusion. They did come to some interesting conclusions: 8 percent of the US population in 2012 had consumed fish oil capsules in the previous 30 days. When they looked at the purity of the supplement they were pleased to find that "the analytical content of EPA and DHA was for the most part reflective of the labeled amounts." They found that free fatty acids were more bioavailable than the products containing ethyl esters. But the more interesting conclusions were:

(a) people who have not had a heart attack, the supplementation with fish oils will not prevent one.

(b) people who have diabetes, and thus at a higher risk of heart attacks, also had no benefit from taking fish oils

(c) people who have a high risk of cardiovascular disease could not conclude that they would have a benefit from taking fish oils

(d) they did recommend people who had had a previous heart attack might benefit from a lower dose of fish oil but their recommendation was a class 2b - meaning the evidence is weak and the usefulness or effectiveness is not known.

(e) There was no reduction in stroke risk by taking fish oil

(f) For people who had a stroke, taking fish oil capsules did not offer protection against a second stroke

(g) For people with heart failure they concluded it was "reasonable" to take fish oil but thought further randomized control trials were needed

This should have been a nail in the coffin for the marketing of fish oil, or fish oil frenzy, but alas, it was not. If you wish to see the full report, it is available online. (Siscovick DS, Barringer TA, Fretts AM, Wu JH, Lichtenstein AH, Costello RB, Kris-Etherton PM, Jacobson TA, Engler MB, Alger HM, Appel LJ, Mozaffarian D; American Heart Association Nutrition Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Epidemiology and Prevention; Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Clinical Cardiology. Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association. Circulation. 2017 Apr 11;135(15):e867-e884. doi: 10.1161/CIR.0000000000000482. Epub 2017 Mar 13. PMID: 28289069; PMCID: PMC6903779)

But that was just conclusions based on many other reports, so the American Heart Association enrolled over 77,000 people in their own trial to quantify the effects of omega-3 fatty acid supplementation on fatal coronary heart disease (CHD), nonfatal heart attacks, stroke, major vascular events, and all-cause mortality. The study was well designed, and it showed no benefit from taking fish oil capsules. From their own words: "This meta-analysis demonstrated that omega-3 fatty acids had no significant association with fatal or nonfatal coronary heart disease or any major vascular events. It provides no support for current recommendations for the use of such supplements in people with a history of coronary heart disease."

Their full report is available if you wish to see it: Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, Geleijnse JM, Rauch B, Ness A, Galan P, Chew EY, Bosch J, Collins R, Lewington S, Armitage J, Clarke R; Omega-3 Treatment Trialists’ Collaboration. Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77 917 Individuals. JAMA Cardiol. 2018 Mar 1;3(3):225-234. doi: 10.1001/jamacardio.2017.5205. PMID: 29387889; PMCID: PMC5885893.

Ultimately it was FISH and not fish oil that has the beneficial effect for cardiac diseases, and to this day you can see the recommendation to have fish in your diet twice a week, which is still in the American Heart Association guidelines.

The role of fish oil and atrial fibrillation

Even to this day, studies will disagree about the value of fish oil for cardiac health. For example, the studies looking at pharmaceutical-grade fish oil, came to different conclusions however there is one conclusion both studies came to: there is an increased risk of atrial fibrillation.

The one study was called REDUCE-IT (Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019 Jan 3;380(1):11-22. doi: 10.1056/NEJMoa1812792. Epub 2018 Nov 10. PMID: 30415628) which concluded that " Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo."

The other study was called STRENGTH which concluded "Among statin-treated patients at high cardiovascular risk, the addition of omega-3 CA, compared with corn oil, to usual background therapies resulted in no significant difference in a composite outcome of major adverse cardiovascular events. These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients." That paper can be seen in its full version (Nicholls SJ, Lincoff AM, Garcia M, Bash D, Ballantyne CM, Barter PJ, Davidson MH, Kastelein JJP, Koenig W, McGuire DK, Mozaffarian D, Ridker PM, Ray KK, Katona BG, Himmelmann A, Loss LE, Rensfeldt M, Lundström T, Agrawal R, Menon V, Wolski K, Nissen SE. Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. JAMA. 2020 Dec 8;324(22):2268-2280. doi: 10.1001/jama.2020.22258. PMID: 33190147; PMCID: PMC7667577)

So a meta-analysis of those studies combined with four other trials looking at omega 3 found that omega-3 supplementation led to a 30 percent increase in the risk of atrial fibrillation. (Lombardi M, Carbone S, Del Buono MG, Chiabrando JG, Vescovo GM, Camilli M, Montone RA, Vergallo R, Abbate A, Biondi-Zoccai G, Dixon DL, Crea F. Omega-3 fatty acids supplementation and risk of atrial fibrillation: an updated meta-analysis of randomized controlled trials. Eur Heart J Cardiovasc Pharmacother. 2021 Jul 23;7(4):e69-e70. doi: 10.1093/ehjcvp/pvab008. PMID: 33910233; PMCID: PMC8302253)

It is a dose-response curve, but even doses as low as 1 gram per day still increased risk of this.

The answer is never over in science because other studies show that the evidence is low, but that there might be positive outcomes from supplementation. (Khan SU, Lone AN, Khan MS, Virani SS, Blumenthal RS, Nasir K, Miller M, Michos ED, Ballantyne CM, Boden WE, Bhatt DL. Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis. EClinicalMedicine. 2021 Jul 8;38:100997. doi: 10.1016/j.eclinm.2021.100997. PMID: 34505026; PMCID: PMC8413259)

Overall?

For those who look at the science of literature, the risk of atrial fibrillation brings to the level of harm for omega-3 supplementation, but not for eating it in food. Meaning, food doesn't cause this as an issue but clearly, the supplements do. Further, it does not matter where the supplements come from.

What food sources are there for omega-3?

Mackerel is a small fatty fish, typically 100 grams (or 3.5 ounces) contains 4100 mg of omega 3 fatty acid per serving. Mackerel also has 200 % of the daily B12 requirement and 100 percent of the selenium requirement.

Salmon is perhaps my favorite. Salmon has 4123 mg per 100 grams or 3.5 ounces. Salmon will lower the risk of heart disease, as well as provide a great source of vitamin D, B, and selenium.

Herring has 946 grams per serving (100 grams or 3.5 ounces) and has 100% of your vitamin D requirement per day.

Those allergic to seafood and to crustaceans often can take mollusks (although please check with your allergists first). But oysters have 370 mg in 6 raw oysters per 100 grams or 3.5 ounces.

Sardines are also helpful with 2,200 in 100 grams or 3.5 ounces. And Anchovies have 351 mg per 100 grams (so that Cesar salad made in the original manner is going to be good for you.

For those that want a non-fish substitute Chia seeds have 5060 per ounce (28 grams) or 2 tablespoons. So 1 tablespoon, which is my typical amount in overnight oats, has 2500 mg.

Flax seeds are also good having 2350 mg per tablespoon in whole seeds.

Walnuts, 2570 mg of omega-3 per 7 walnuts or ounce.

Even soybeans, which are a healthy legume, contain 670 mg in 1/2 cup or 1443 per 100 grams. Edamame is more than a snack!

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Fork U is part of the Your Doctors Orders network of podcasts and is hosted by noted physician and surgeon Dr. Terry Simpson.

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Fork U is produced by Simpler Media and is recorded in the studios of ProducerGirl Productions.

Fork U: The latest podcast from Dr. Terry Simpson Sep 20, 2021

Show notes

Welcome to Fork U, the latest podcast from Dr. Terry Simpson.

If you enjoyed the previous episodes of Culinary Medicine and Your Doctors Orders, you'll love these quick, impactful bits of information that are easily digestible. (See what I did there?)

No need to adjust your podcast or subscribe to anything new, you are already here!

With that, here is the first episode of the new podcast, Fork U, where you can learn a bit about food and medicine.