Ep. 5: Prof. Tom Brenna, Omega 3 and Omega 6 in Human Health—with Dr Brian Kerley

Human results of a low-linoleic diet with adequate omega-3 on neurodevelopment. The WHO change their guidelines. How to protect against blindness. Why the Dietary Guidelines can't get it right, and where they do. Fish vs fish oil for omega-3 DHA benefits. Fish consumption and mercury, is it a problem? Farmed vs. wild-caught fish. On the essentiality of linoleic acid. Linoleic acid impairs fertility Biography: Tom Brenna, Ph.D., Professor, Department of Pediatrics, Dell Medical School, UT Austin; https://dellmed.utexas.edu/directory/tom-brenna "Tom Brenna is a professor of pediatrics at Dell Medical School. He moved to Austin after 28 years as a professor of human nutrition, chemistry, chemical biology and food science at Cornell University in Ithaca, New York. His group's basic research into the chemical, biochemical, metabolic, genetic and ecological aspects of fatty acids have had a decisive influence on modern knowledge of these key nutrients. "Brenna's research couples nutrition and chemistry in a broadly interdisciplinary program. His research group has been funded by institutes and centers at the National Institutes of Health (National Institute of General Medical Sciences, National Eye Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Center for Complementary and Integrative Health) since 1992. Most of the work of the Brenna Lab is translational, tying basic research to biomedicine and human nutrition…." Professor Emeritus, Division of Nutritional Sciences, Cornell University. https://www.human.cornell.edu/people/jtb4 _______________________________________ Co-host Dr. Brian Kerley https://www.seedoilrebellion.com/ https://twitter.com/SeedOilDsrspctr   Looking to fix your diet by getting rid of seed oils? Check out the Seedy app! https://www.seedyapp.com/   Tucker Goodrich Blog: http://yelling-stop.blogspot.com/ Youtube: https://www.youtube.com/channel/UCDpWmYeRapRkrZ9zw8M7iFg Podcast: https://sites.libsyn.com/408758 Twitter: https://twitter.com/TuckerGoodrich _______________________________________ Show Notes Nina Teicholz' organization is The Nutrition Coalition. https://www.nutritioncoalition.us/ Q: "What are you working on right now? What the most recent and interesting thing that you have published?" RCT of low-linoleic therapeutic foods: Stephenson, K., Callaghan-Gillespie, M., Maleta, K., Nkhoma, M., George, M., Park, H. G., Lee, R., Humpheries-Cuff, I., Lacombe, R. J. S., Wegner, D. R., Canfield, R. L., Brenna, J. T., & Manary, M. J. (2021). Low linoleic acid foods with added DHA given to Malawian children with severe acute malnutrition improve cognition: A randomized, triple blinded, controlled clinical trial. The American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqab363 Hsieh, J.-C., Liu, L., Zeilani, M., Ickes, S., Trehan, I., Maleta, K., Craig, C., Thakwalakwa, C., Singh, L., Brenna, J. T., & Manary, M. J. (2015). High-Oleic Ready-to-Use Therapeutic Food Maintains Docosahexaenoic Acid Status in Severe Malnutrition. Journal of Pediatric Gastroenterology and Nutrition, 61(1), 138–143. https://doi.org/10.1097/MPG.0000000000000741 Codex Alimentarius: New Ready-to-Use Therapeutic Foods guidelines. https://www.fao.org/fao-who-codexalimentarius/news-and-events/news-details/en/c/1458680/ "WHO summary on the available evidence for the essential fatty acid profiles in ready-to-use therapeutic foods for treating children with severe wasting" https://www.fao.org/fao-who-codexalimentarius/sh-proxy/en/?lnk=1&url=https%253A%252F%252Fworkspace.fao.org%252Fsites%252Fcodex%252FMeetings%252FCX-720-42%252FLinks%252FWHO_summary_on_EFA_in_RUTF.pdf Saturated fat and cardiovascular disease: "Saturated Fats and Health: A Reassessment and Proposal for Food-based Recommendations: JACC State-of -the-Art Review": * http://www.sciencedirect.com/science/article/pii/S0735109720356874 "Though no human randomized controlled trials on minimal omega-3 requirements in pregnancy and lactation have been conducted, the weight of animal evidence compellingly shows that randomizing pregnant or lactating humans to diets that include high linoleate oils as the sole source of fat would be frankly unethical because they would result in suboptimal child development." Brenna, J. T. (2011). Animal studies of the functional consequences of suboptimal polyunsaturated fatty acid status during pregnancy, lactation and early post-natal life. Maternal & Child Nutrition, 7 Suppl 2, 59–79. https://doi.org/10.1111/j.1740-8709.2011.00301.x "Put another way, only 2 ways are known to increase circulating DHA status in humans: 1) consume (preformed) DHA, or 2) lower dietary LA." Kothapalli, K. S. D., Park, H. G., & Brenna, J. T. (2020). Polyunsaturated fatty acid biosynthesis pathway and genetics. Implications for interindividual variability in prothrombotic, inflammatory conditions such as COVID-19. Prostaglandins, Leukotrienes and Essential Fatty Acids, 162, 102183. https://doi.org/10.1016/j.plefa.2020.102183 "We generated a paper showing that that is the case, back in 2007 or 2009. I think it's this, since the last sentence is "Present evidence indicates that n-3 LCPUFA status can be improved by increasing their intake or by decreasing LA intake, and a combination of the two is likely to be most effective.": Brenna, J. T., Salem, N., Sinclair, A. J., & Cunnane, S. C. (2009). α-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins, Leukotrienes and Essential Fatty Acids, 80(2), 85–91. https://doi.org/10.1016/j.plefa.2009.01.004 "That's why the story of just having a ratio between omega-6 and omega-3 is just not a way to think about this as a general concept. If you increase [non-DHA] omega-3 you don't get more DHA, but if you decrease omega-6 linoleic, you do get more. "Would you like an update on that? We found a third way…" Klatt, K. C., McDougall, M. Q., Malysheva, O. V., Taesuwan, S., Loinard-González, A. (Alex) P., Nevins, J. E. H., Beckman, K., Bhawal, R., Anderson, E., Zhang, S., Bender, E., Jackson, K. H., King, D. J., Dyer, R. A., Devapatla, S., Vidavalur, R., Brenna, J. T., & Caudill, M. A. (2022). Prenatal choline supplementation improves biomarkers of maternal docosahexaenoic acid status among pregnant participants consuming supplemental DHA: A randomized controlled trial. The American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqac147 "we had done studies in the 1990s, and followed up after the turn of the millennium, that showed that just with oils you get a better targeting of DHA and another n-3 that's important, arachidonic acid [AA, I think he is mis-speaking here, as AA is n-6, not n-3] to the brain if they come in as a phospholipid and not a tryglyceride. Cunnane, S. C. (2002). Arachidonate metabolism in neonates. Pediatric Research, 51(3), 263–264. https://doi.org/10.1203/00006450-200203000-00001 Wijendran, V., Huang, M.-C., Diau, G.-Y., Boehm, G., Nathanielsz, P. W., & Brenna, J. T. (2002). Efficacy of dietary arachidonic acid provided as triglyceride or phospholipid as substrates for brain arachidonic acid accretion in baboon neonates. Pediatric Research, 51(3), 265–272. https://doi.org/10.1203/00006450-200203000-00002 Zhang, Q., Wu, W. X., Nathanielsz, P. W., & Brenna, J. T. (1995). Distribution of arachidonic, eicosapentaenoic, docosahexaenoic and related fatty acids in ovine endometrial phospholipids in late gestation and labor. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 53(3), 201–209. https://doi.org/10.1016/0952-3278(95)90117-5 "This one is a much more technological. I will explain it, and I will also say that I have a bit of a business interest… in the company that's doing this…." "DHA and all PUFAs are well known to be susceptible to oxidation…" Liu, Y., Bell, B. A., Song, Y., Zhang, K., Anderson, B., Axelsen, P. H., Bohannan, W., Agbaga, M.-P., Park, H. G., James, G., Brenna, J. T., Schmidt, K., Dunaief, J. L., & Shchepinov, M. S. (2022). Deuterated docosahexaenoic acid protects against oxidative stress and geographic atrophy-like retinal degeneration in a mouse model with iron overload. Aging Cell, 21(4), e13579. https://doi.org/10.1111/acel.13579 Q: "Why is consuming more linoleic acid reducing DHA in the body?" A:           Mohrhauer, H., & Holman, R. T. (1963). The effect of dose level of essential fatty acids upon fatty acid composition of the rat liver *. Journal of Lipid Research, 4(2), 151–159. https://doi.org/10.1016/S0022-2275(20)40341-4 Paper that introduced omega nomenclature for fats: Holman, R. T. (1964). Nutritional And Metabolic Interrelationships Between Fatty Acids. Federation Proceedings, 23, 1062–1067. Zhang, J. Y., Kothapalli, K. S. D., & Brenna, J. T. (2016). Desaturase and elongase limiting endogenous long chain polyunsaturated fatty acid biosynthesis. Current Opinion in Clinical Nutrition and Metabolic Care, 19(2), 103–110. https://doi.org/10.1097/MCO.0000000000000254 Q: "Interesting. But you would think based on that… Let's touch on your experience with the dietary guidelines a little bit, you would think that that would be reflected in some of the recommendations on how we eat." A:           Astrup, A., Teicholz, N., Magkos, F., Bier, D. M., Brenna, J. T., King, J. C., Mente, A., Ordovas, J. M., Volek, J. S., Yusuf, S., & Krauss, R. M. (2021). Dietary Saturated Fats and Health: Are the U.S. Guidelines Evidence-Based? Nutrients, 13(10), 3305. https://doi.org/10.3390/nu13103305 McGovern Report 1977: Needs, U. S. C. S. S. C. on N. and H., & Mottern, N. (1977). Dietary Goals for the United States. U.S. Government Printing Office. https://www.google.com/books/edition/Dietary_Goals_for_the_United_States/kNH4BNDQETQC?hl=en Sandy, D. B. (1989). The Production and Use of Vegetable Oils in Ptolemaic Egypt. Scholars Press. https://www.google.com/books/edition/The_Production_and_Use_of_Vegetable_Oils/mg1tQgAACAAJ?hl=en NEED TO SEND TO BRENNA Menayang, A. (2017, April 30). Mars pledges to use 100% high-oleic peanuts in M&Ms, Munch Bar, by end of 2017. Foodnavigator-Usa.Com. https://www.foodnavigator-usa.com/Article/2017/05/01/Mars-and-peanut-industry-to-use-only-high-oleic-peanuts-in-products O'Keefe, S. F., Wiley, V. A., & Knauft, D. A. (1993). Comparison of oxidative stability of high- and normal-oleic peanut oils. Journal of the American Oil Chemists' Society, 70(5), 489–492. https://doi.org/10.1007/BF02542581 Q: "What's a plausible dream study you would like to perform?" Gornoski, D. (2021, October 3). Professor Ameer Taha on Lipid Oxidation, Linoleic Acid, OXLAMS (No. 2021-10–03) [Mp3]. https://aneighborschoice.com/professor-ameer-taha-on-lipid-oxidation-linoleic-acid-oxlams/ Ramsden's headache studies: Mann, J. D., Faurot, K. R., MacIntosh, B., Palsson, O. S., Suchindran, C. M., Gaylord, S. A., Lynch, C., Johnston, A., Maiden, K., Barrow, D. A., Hibbeln, J. R., & Ramsden, C. E. (2018). A sixteen-week three-armed, randomized, controlled trial investigating clinical and biochemical effects of targeted alterations in dietary linoleic acid and n-3 EPA+DHA in adults with episodic migraine: Study protocol. Prostaglandins, Leukotrienes and Essential Fatty Acids, 128, 41–52. https://doi.org/10.1016/j.plefa.2017.11.002 Ramsden, C. E., Domenichiello, A. F., Yuan, Z.-X., Sapio, M. R., Keyes, G. S., Mishra, S. K., Gross, J. R., Majchrzak-Hong, S., Zamora, D., Horowitz, M. S., Davis, J. M., Sorokin, A. V., Dey, A., LaPaglia, D. M., Wheeler, J. J., Vasko, M. R., Mehta, N. N., Mannes, A. J., & Iadarola, M. J. (2017). A systems approach for discovering linoleic acid derivatives that potentially mediate pain and itch. Science Signaling, 10(493). https://doi.org/10.1126/scisignal.aal5241 Ramsden, C. E., Faurot, K. R., Zamora, D., Suchindran, C. M., MacIntosh, B. A., Gaylord, S., Ringel, A., Hibbeln, J. R., Feldstein, A. E., Mori, T. A., Barden, A., Lynch, C., Coble, R., Mas, E., Palsson, O., Barrow, D. A., & Mann, D. J. (2013). Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: A randomized trial. Pain, 154(11), 2441–2451. https://doi.org/10.1016/j.pain.2013.07.028 Ramsden, C. E., Ringel, A., Feldstein, A. E., Taha, A. Y., MacIntosh, B. A., Hibbeln, J. R., Majchrzak-Hong, S. F., Faurot, K. R., Rapoport, S. I., Cheon, Y., Chung, Y.-M., Berk, M., & Douglas Mann, J. (2012). Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans. Prostaglandins, Leukotrienes and Essential Fatty Acids, 87(4), 135–141. https://doi.org/10.1016/j.plefa.2012.08.004 Ramsden, C. E., Zamora, D., Faurot, K. R., MacIntosh, B., Horowitz, M., Keyes, G. S., Yuan, Z.-X., Miller, V., Lynch, C., Honvoh, G., Park, J., Levy, R., Domenichiello, A. F., Johnston, A., Majchrzak-Hong, S., Hibbeln, J. R., Barrow, D. A., Loewke, J., Davis, J. M., … Mann, J. D. (2021). Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: Randomized controlled trial. BMJ, 374, n1448. https://doi.org/10.1136/bmj.n1448 Q: COVID-19 paper: Kothapalli, K. S. D., Park, H. G., & Brenna, J. T. (2020). Polyunsaturated fatty acid biosynthesis pathway and genetics. Implications for interindividual variability in prothrombotic, inflammatory conditions such as COVID-19. Prostaglandins, Leukotrienes and Essential Fatty Acids, 162, 102183. https://doi.org/10.1016/j.plefa.2020.102183 Goodrich, T. (2020, June 2). Does Consumption of Omega-6 Seed Oils Worsen ARDS and COVID-19? [Blog]. Yelling Stop. http://yelling-stop.blogspot.com/2020/06/does-consumption-of-omega-6-seed-oils.html Dyerberg, J., & Jørgensen, K. A. (1982). Marine oils and thrombogenesis. Progress in Lipid Research, 21(4), 255–269. https://doi.org/10.1016/0163-7827(82)90011-X McReynolds, C. B., Cortes-Puch, I., Ravindran, R., Khan, I. H., Hammock, B. G., Shih, P. B., Hammock, B. D., & Yang, J. (2021). Plasma Linoleate Diols Are Potential Biomarkers for Severe COVID-19 Infections. Frontiers in Physiology, 12. https://doi.org/10.3389/fphys.2021.663869 Quote from Ralph Holman: "It seems reasonable to suggest that 18:3w3 intake be increased during pregnancy, lactation, and infancy, when the requirements for w3 PUFA are highest, during the development of the nervous system, which is rich in lipids containing high proportions of c3 PUFA. The mental apparatus of the coming generation is developed in utero, and the time to begin supplementation is before conception. A normal brain cannot be made without an adequate supply of w3 PUFA, and there may be no later opportunity to repair the effects of an w3 fatty acid deficiency once the nervous system is formed." Holman, R. T., Johnson, S. B., & Ogburn, P. L. (1991). Deficiency of essential fatty acids and membrane fluidity during pregnancy and lactation. Proceedings of the National Academy of Sciences of the United States of America, 88(11), 4835–4839. https://doi.org/10.1073/pnas.88.11.4835 Q: Seafood Nutrition Partnership: https://www.seafoodnutrition.org/ Tom's bio there: https://www.seafoodnutrition.org/profile/tom-brenna/ Hibbeln, J. R., Spiller, P., Brenna, J. T., Golding, J., Holub, B. J., Harris, W. S., Kris-Etherton, P., Lands, B., Connor, S. L., Myers, G., Strain, J. J., Crawford, M. A., & Carlson, S. E. (2019). Relationships between seafood consumption during pregnancy and childhood and neurocognitive development: Two systematic reviews. Prostaglandins, Leukotrienes and Essential Fatty Acids, 151, 14–36. https://doi.org/10.1016/j.plefa.2019.10.002 Seychelles study (not Mauritius): Davidson, P. W., Leste, A., Benstrong, E., Burns, C. M., Valentin, J., Sloane-Reeves, J., Huang, L.-S., Miller, W. A., Gunzler, D., van Wijngaarden, E., Watson, G. E., Zareba, G., Shamlaye, C. F., & Myers, G. J. (2010). Fish consumption, mercury exposure, and their associations with scholastic achievement in the Seychelles Child Development Study. NeuroToxicology, 31(5), 439–447. https://doi.org/10.1016/j.neuro.2010.05.010 Q: "Talk to us a little bit about farmed vs. wild-caught fish. That's a big thing in the ancestral health community.": Nichols, P. D., Glencross, B., Petrie, J. R., & Singh, S. P. (2014). Readily Available Sources of Long-Chain Omega-3 Oils: Is Farmed Australian Seafood a Better Source of the Good Oil than Wild-Caught Seafood? Nutrients, 6(3), 1063–1079. https://doi.org/10.3390/nu6031063 P.S. Discussion of Mark's Puder's research: Anez-Bustillos, L., Dao, D. T., Fell, G. L., Baker, M. A., Gura, K. M., Bistrian, B. R., & Puder, M. (2018). Redefining essential fatty acids in the era of novel intravenous lipid emulsions. Clinical Nutrition, 37(3), 784–789. https://doi.org/10.1016/j.clnu.2017.07.004 Carlson, S. J., O'Loughlin, A. A., Anez-Bustillos, L., Baker, M. A., Andrews, N. A., Gunner, G., Dao, D. T., Pan, A., Nandivada, P., Chang, M., Cowan, E., Mitchell, P. D., Gura, K. M., Fagiolini, M., & Puder, M. (2019). A Diet With Docosahexaenoic and Arachidonic Acids as the Sole Source of Polyunsaturated Fatty Acids Is Sufficient to Support Visual, Cognitive, Motor, and Social Development in Mice. Frontiers in Neuroscience, 13, 72. https://doi.org/10.3389/fnins.2019.00072 "Mouse-o-pause", mouse menopause: Nehra, D., Le, H. D., Fallon, E. M., Carlson, S. J., Woods, D., White, Y. A., Pan, A. H., Guo, L., Rodig, S. J., Tilly, J. L., Rueda, B. R., & Puder, M. (2012). Prolonging the female reproductive lifespan and improving egg quality with dietary omega-3 fatty acids. Aging Cell, 11(6), 1046–1054. https://doi.org/10.1111/acel.12006 Cunnane, S. C. (2003). Problems with essential fatty acids: Time for a new paradigm? Progress in Lipid Research, 42(6), 544–568. https://doi.org/10.1016/S0163-7827(03)00038-9 Quotable: "The general idea that we call Evidence-Based Medicine, which, I'm afraid eliminates 95% of all the evidence that informs nutrition, and focuses 100% on human studies. Human studies are the worst studies. They are by far the worst. I don't think it's possible that a serious argument can be made otherwise." "The food industry is not a bunch of evil guys who are just out to take everybody's money… So I'm not here to beat up food companies." "Coconut's a seed, but it's a weird seed." "Some species [of fish] will eat grain, and if they eat grain, then their fatty-acid profile will look like the grain you feed them." "Salmon have the good sense to die if you don't feed them DHA." "Farmed fish actually had a higher amount of DHA than the wild caught." Brenna's Industrial Food Principle: "When we produce animal foods, their nutrient profile should match that of the wild-caught." "It sounds like you're saying you're better off eating a farm-raised salmon than an industrially-raised chicken?" "Yeah, I'm probably going to get in trouble for saying that, but I think that's probably right." "Otherwise, you've got the cheapest food in the world and the most expensive medicines in the world. Family physicians don't like stuff like that; pediatricians don't like stuff like that. We want to feed people well, and worry about medicine in well-fed people, rather than having to correct nutrient deficiencies by giving them drugs." "Low linoleic acid maintains fertility." "You'll often read in the medical literature that linoleic and alpha-linolenic are essential, and DHA and arachidonic are conditionally essential, and it sounds like they got it backwards." "They do. And it's a meme has never died, from the 1950s."