Interview: "Seed Oil Research with Prof. Bruce Hammock, Prof. Bruce German, and Tucker Goodrich" on A Neighbor's Choice with David Gornoski

For a change, I'm doing the interviewing, thanks to David who arranged this. A really mind-bending discussion.

"In this special roundtable podcast, David Gornoski and nutritional researcher Tucker Goodrich talk with distinguished professors Bruce Hammock and J Bruce German to discuss what their research of linoleic acid has revealed about our immune system, severe burns, pain blockers, ARDS mortality, mass consumption of vegetable oils, and more. How can we increase Omega-3 fatty acids without increasing Omega-6 in our bodies? Does decreasing Omega-6 in our bodies also decrease the susceptibility to severe cases of COVID?

"Bruce Hammock PhD is the Distinguished Professor of Entomology and UCD Comprehensive Cancer Center and Director of the NIEHS-UCD Superfund Research Program at University of California, Davis. "J. Bruce German PhD is a chemist and food scientist at UC, Davis. Professor German researches the role of fats and other components in the diet.

(I will update this post if I get any new info, there are a few missing references below.

P.S. Finished the show notes, 32 and above are new. Still missing a few references.)

It's probably better to watch the video if you can, there's a lot of non-verbal communication going on!

Here's the podcast:

And here's the direct link to ANC.

Show notes:

Bruce D. Hammock: Hammock Laboratory of Pesticide Biotechnology

J. Bruce German

References in order of mention (see the names in the references section below for links to the study):

1. Hammock recent research on leuktoxin and COVID-19: (McReynolds, Cortes_Puch, et al., 2021; McReynolds, Cortes-Puch, et al., 2021).
2.  Japanese research on burns and leukotoxin: (Hayakawa et al., 1990; Kosaka et al., 1994).
3. Diols, not epoxides are the actual toxin: (Moghaddam et al., 1997; Zheng et al., 1998)
4. Stearic acid in plaques of American soldiers in Korean war: TK
5. Crocodile oil study: (Watkins et al., 2001)
6. Leukotoxin and brown fat: (Kulterer et al., n.d.; Lynes et al., 2017)
7. N-6 (omega-6) PUFA and ARDS survival: (Bursten et al., 1996)
8. Arachidonic acid metabolic pathways: (Hildreth et al., 2020)
9. "Seventy-five percent, by weight, of the drugs sold in the world: (Rice, 2020)
10. COX and LOX inflammatory pathways: (Archambault et al., 2020).
11. Discovery of soluble Epoxide Hydrolase (sEH): (Kodani & Hammock, 2015)
12. sEH, horses, and tendonitis (laminitis): (Guedes et al., 2013; Rice, 2020)
13. Human trials of sEH inhibitor: (Hammock et al., 2021)
14. Diabetic pain & neuropathy: TK
15. Bill (William E. M.) Lands: (Wikipedia, 2020)
16. Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 [n-3] polyunsaturated fatty acids in human plasma lipid pools: (Taha et al., 2014)
17. Age-related Macular Degeneration and N-6: TK
18. "We're funded by the National Institutes of Drug Abuse"... (Hammock et al., 2021)
19. Excess linoleic acid: (Okuyama et al., 1996)
20. Fred Kummerow: trans fats researcher, on his diet: (Kummerow, 2015)
21. Vernoleate bursting into flames, "another name for leukotoxin": (Bafor et al., 1993)
22. Synthetic n-3 and farmed fish: (Kitessa et al., 2014)
23. "The Environmental Impact of Vegetable Oils": (Nobbs, 2021)
24. Dog study on leukotoxin: (Fukushima et al., 1988)
25. Elevated leukotoxin in CVD and T2DM: TK
26. N-6, sEH, and dementia ("Walter Swardfager in Toronto"): (Yu et al., 2019)
27. HNE inducing amyloid plaque: (Arimon et al., 2015)
28. Unsaturated aldehydes and tear gas: (Corson & Stoughton, 1928)
29. Omega-3 and COVID-19: (Arnardottir et al., 2021)
30. ARDS and trauma victims: (Plurad et al., 2009)
31. John Kinsella and ARDS (may not be right paper): (Riyami et al., 1990)
32. Kathleen Gura and Omega-6 infusions: (de Meijer et al., 2010)
33. K-rations and Ancel Keys: (Oliver, 2004)
34. Ancel Keys and Minnesota Coronary Experiment: (Ramsden et al., 2016)
35.  Seed oils and torpor/hibernation: (Geiser & Kenagy, 1987; Ruf & Geiser, 2015)
36. Linoleic acid diols and hibernation: TK
37. Susan Allport, linoleic acid lowers BMR: (Allport, 2010)
38. sEH and diabetes; sEH with n-3 eliminates T2DM w/ less n-6 (work by "Joan de Clerin"?): TK
39. Mothers and babies: (German, 2011)
40. Generational effects of high n-6: (Mamounis et al., 2020)
41. Breast milk high in omega-6 (Tsimane vs American): (Martin et al., 2012)
42. Bill Lands "NIX6 and EAT3" web site: EFAEducation.org

References:

Allport, S. (2010, November). One person’s response to a high omega-6 diet [Magazine]. American Oil Chemists’ Society. https://www.aocs.org/stay-informed/inform-magazine/featured-articles/one-persons-response-to-a-high-omega-6-diet-november-2010?SSO=True

Archambault, A.-S., Zaid, Y., Rakotoarivelo, V., Doré, É., Dubuc, I., Martin, C., Amar, Y., Cheikh, A., Fares, H., Hassani, A. E., Tijani, Y., Laviolette, M., Boilard, É., Flamand, L., & Flamand, N. (2020). Lipid storm within the lungs of severe COVID-19 patients: Extensive levels of cyclooxygenase and lipoxygenase-derived inflammatory metabolites. MedRxiv, 2020.12.04.20242115. https://doi.org/10.1101/2020.12.04.20242115

Arimon, M., Takeda, S., Post, K. L., Svirsky, S., Hyman, B. T., & Berezovska, O. (2015). Oxidative stress and lipid peroxidation are upstream of amyloid pathology. Neurobiology of Disease, 84, 109–119. https://doi.org/10.1016/j.nbd.2015.06.013

Arnardottir, H., Pawelzik, S.-C., Öhlund Wistbacka, U., Artiach, G., Hofmann, R., Reinholdsson, I., Braunschweig, F., Tornvall, P., Religa, D., & Bäck, M. (2021). Stimulating the Resolution of Inflammation Through Omega-3 Polyunsaturated Fatty Acids in COVID-19: Rationale for the COVID-Omega-F Trial. Frontiers in Physiology, 11. https://doi.org/10.3389/fphys.2020.624657

Bafor, M., Smith, M. A., Jonsson, L., Stobart, K., & Stymne, S. (1993). Biosynthesis of vernoleate (cis-12-epoxyoctadeca-cis-9-enoate) in microsomal preparations from developing endosperm of Euphorbia lagascae. Archives of Biochemistry and Biophysics, 303(1), 145–151. https://doi.org/10.1006/abbi.1993.1265

Bursten, S. L., Federighi, D. A., Parsons, P. E., Harris, W. E., Abraham, E., Moore, E. E. J., Moore, F. A., Bianco, J. A., Singer, J. W., & Repine, J. E. (1996). An increase in serum C18 unsaturated free fatty acids as a predictor of the development of acute respiratory distress syndrome. Read Online: Critical Care Medicine | Society of Critical Care Medicine, 24(7), 1129–1136. https://doi.org/10.1097/00003246-199607000-00011

Corson, B. B., & Stoughton, R. W. (1928). REACTIONS OF ALPHA, BETA-UNSATURATED DINITRILES. Journal of the American Chemical Society. https://doi.org/10.1021/ja01397a037

de Meijer, V. E., Le, H. D., Meisel, J. A., Gura, K. M., & Puder, M. (2010). Parenteral Fish Oil as Monotherapy Prevents Essential Fatty Acid Deficiency in Parenteral Nutrition Dependent Patients. Journal of Pediatric Gastroenterology and Nutrition, 50(2), 212–218. https://doi.org/10.1097/MPG.0b013e3181bbf51e

Fukushima, A., Hayakawa, M., Sugiyama., S., Ajioka, M., Ito, T., Satake, T., & Ozawa, T. (1988). Cardiovascular effects of leukotoxin (9,10-epoxy-12-octadecenoate) and free fatty acids in dogs. Cardiovascular Research, 22(3), 213–218. https://doi.org/10.1093/cvr/22.3.213

Geiser, F., & Kenagy, G. J. (1987). Polyunsaturated lipid diet lengthens torpor and reduces body temperature in a hibernator. The American Journal of Physiology, 252(5 Pt 2), R897-901. https://doi.org/10.1152/ajpregu.1987.252.5.R897

German, J. B. (2011). Dietary lipids from an evolutionary perspective: Sources, structures and functions. Maternal & Child Nutrition, 7(s2), 2–16. https://doi.org/10.1111/j.1740-8709.2011.00300.x

Guedes, A. G., Morisseau, C., Sole, A., Soares, J. H., Ulu, A., Dong, H., & Hammock, B. D. (2013). Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis. Veterinary Anaesthesia and Analgesia, 40(4), 440–448. https://doi.org/10.1111/vaa.12030

Hammock, B. D., McReynolds, C. B., Wagner, K., Buckpitt, A., Cortes-Puch, I., Croston, G., Lee, K. S. S., Yang, J., Schmidt, W. K., & Hwang, S. H. (2021). Movement to the Clinic of Soluble Epoxide Hydrolase Inhibitor EC5026 as an Analgesic for Neuropathic Pain and for Use as a Nonaddictive Opioid Alternative. Journal of Medicinal Chemistry, 64(4), 1856–1872. https://doi.org/10.1021/acs.jmedchem.0c01886

Hayakawa, M., Kosaka, K., Sugiyama, S., Yokoo, K., Aoyama, H., Izawa, Y., & Ozawa, T. (1990). Proposal of leukotoxin, 9,10-epoxy-12-octadecenoate, as a burn toxin. Biochemistry International, 21(3), 573–579. https://pubmed.ncbi.nlm.nih.gov/2222499/

Hildreth, K., Kodani, S. D., Hammock, B. D., & Zhao, L. (2020). Cytochrome P450-derived linoleic acid metabolites EpOMEs and DiHOMEs: A review of recent studies. The Journal of Nutritional Biochemistry, 86, 108484. https://doi.org/10.1016/j.jnutbio.2020.108484

Kitessa, S. M., Abeywardena, M., Wijesundera, C., & Nichols, P. D. (2014). DHA-Containing Oilseed: A Timely Solution for the Sustainability Issues Surrounding Fish Oil Sources of the Health-Benefitting Long-Chain Omega-3 Oils. Nutrients, 6(5), 2035–2058. https://doi.org/10.3390/nu6052035

Kodani, S. D., & Hammock, B. D. (2015). The 2014 Bernard B. Brodie award lecture-epoxide hydrolases: Drug metabolism to therapeutics for chronic pain. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 43(5), 788–802. https://doi.org/10.1124/dmd.115.063339

Kosaka, K., Suzuki, K., Hayakawa, M., Sugiyama, S., & Ozawa, T. (1994). Leukotoxin, a linoleate epoxide: Its implication in the late death of patients with extensive burns. Molecular and Cellular Biochemistry, 139(2), 141–148. https://doi.org/10.1007/BF01081737

Kulterer, O. C., Niederstaetter, L., Herz, C. T., Haug, A. R., Bileck, A., Pils, D., Kautzky-Willer, A., Gerner, C., & Kiefer, F. W. (n.d.). The presence of active brown adipose tissue determines cold-induced energy expenditure and oxylipin profiles in humans. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/clinem/dgaa183

Kummerow, F. (2015, February). My Diet. World Nutrition. http://archive.wphna.org/wp-content/uploads/2015/01/WN-2015-06-01-02-72-78-Idea-Fred-Kummerow-My-diet-JF.pdf

Lynes, M. D., Leiria, L. O., Lundh, M., Bartelt, A., Shamsi, F., Huang, T. L., Takahashi, H., Hirshman, M. F., Schlein, C., Lee, A., Baer, L. A., May, F. J., Gao, F., Narain, N. R., Chen, E. Y., Kiebish, M. A., Cypess, A. M., Blüher, M., Goodyear, L. J., … Tseng, Y.-H. (2017). The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue. Nature Medicine, 23(5), 631–637. https://doi.org/10.1038/nm.4297

Mamounis, K. J., Shvedov, N. R., Margolies, N., Yasrebi, A., & Roepke, T. A. (2020). The effects of dietary fatty acids in the physiological outcomes of maternal high-fat diet on offspring energy homeostasis in mice. Journal of Developmental Origins of Health and Disease, 11(3), 273–284. https://doi.org/10.1017/S2040174419000540

Martin, M. A., Lassek, W. D., Gaulin, S. J. C., Evans, R. W., Woo, J. G., Geraghty, S. R., Davidson, B. S., Morrow, A. L., Kaplan, H. S., & Gurven, M. D. (2012). Fatty acid composition in the mature milk of Bolivian forager-horticulturalists: Controlled comparisons with a US sample. Maternal & Child Nutrition, 8(3). https://doi.org/10.1111/j.1740-8709.2012.00412.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

McReynolds, C. B., Cortes_Puch, I., Ravindran, R., Khan, I., Shih, P.-A. B., Hammock, B. D., Yang, J., & Hammock, B. G. (2021). Lipid mediators detected in COVID-19 patients and healthy controls (Version 4, p. 135850 bytes) [Data set]. Dryad. https://doi.org/10.25338/B8M92X

Moghaddam, M. F., Grant, D. F., Cheek, J. M., Greene, J. F., Williamson, K. C., & Hammock, B. D. (1997). Bioactivation of leukotoxins to their toxic diols by epoxide hydrolase. Nature Medicine, 3(5), 562–566. https://doi.org/10.1038/nm0597-562

Nobbs, J. (2021, March 30). The Environmental Impact of Vegetable Oils [Blog]. Jeff Nobbs. https://www.jeffnobbs.com/posts/the-environmental-impact-of-vegetable-oils

Okuyama, H., Kobayashi, T., & Watanabe, S. (1996). Dietary fatty acids—The n-6n-3 balance and chronic elderly diseases. Excess linoleic acid and relative n-3 deficiency syndrome seen in Japan. Progress in Lipid Research, 35(4), 409–457. https://doi.org/10.1016/S0163-7827(96)00012-4

Oliver, M. (2004, November 25). Ancel Keys, 100; Diet Researcher Developed K-Rations for Troops. Los Angeles Times. https://www.latimes.com/archives/la-xpm-2004-nov-25-me-keys25-story.html

Plurad, D., Green, D., Inaba, K., Belzberg, H., Demetriades, D., & Rhee, P. (2009). A 6-year review of total parenteral nutrition use and association with late-onset acute respiratory distress syndrome among ventilated trauma victims. Injury, 40(5), 511–515. https://doi.org/10.1016/j.injury.2008.07.025

Ramsden, C. E., Zamora, D., Majchrzak-Hong, S., Faurot, K. R., Broste, S. K., Frantz, R. P., Davis, J. M., Ringel, A., Suchindran, C. M., & Hibbeln, J. R. (2016). Re-evaluation of the traditional diet-heart hypothesis: Analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ, 353. https://doi.org/10.1136/bmj.i1246

Rice, M. E. (2020). Bruce D. Hammock: Science Should Be Fun. American Entomologist, 66(1), 14–19. https://doi.org/10.1093/ae/tmaa010

Riyami, B. M., Tree, R., Kinsella, J., Clark, C. J., Reid, W. H., Campbell, D., & Gemmell, C. G. (1990). Changes in alveolar macrophage, monocyte, and neutrophil cell profiles after smoke inhalation injury. Journal of Clinical Pathology, 43(1), 43–45. https://doi.org/10.1136/jcp.43.1.43

Ruf, T., & Geiser, F. (2015). Daily torpor and hibernation in birds and mammals. Biological Reviews, 90(3), 891–926. https://doi.org/10.1111/brv.12137

Taha, A. Y., Cheon, Y., Faurot, K. F., MacIntosh, B., Majchrzak-Hong, S. F., Mann, J. D., Hibbeln, J. R., Ringel, A., & Ramsden, C. E. (2014). Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 90(5), 151–157. https://doi.org/10.1016/j.plefa.2014.02.003

Watkins, S. M., Lin, T. Y., Davis, R. M., Ching, J. R., DePeters, E. J., Halpern, G. M., Walzem, R. L., & German, J. B. (2001). Unique phospholipid metabolism in mouse heart in response to dietary docosahexaenoic or α-linolenic acids. Lipids, 36(3), 247–254. https://doi.org/10.1007/s11745-001-0714-8

Wikipedia. (2020). William E.M. Lands. In Wikipedia. https://en.wikipedia.org/w/index.php?title=William_E.M._Lands&oldid=994164694

Yu, D., Hennebelle, M., Sahlas, D. J., Ramirez, J., Gao, F., Masellis, M., Cogo-Moreira, H., Swartz, R. H., Herrmann, N., Chan, P. C., Pettersen, J. A., Stuss, D. T., Black, S. E., Taha, A. Y., & Swardfager, W. (2019). Soluble Epoxide Hydrolase-Derived Linoleic Acid Oxylipins in Serum Are Associated with Periventricular White Matter Hyperintensities and Vascular Cognitive Impairment. Translational Stroke Research, 10(5), 522–533. https://doi.org/10.1007/s12975-018-0672-5

Zheng, J., Plopper, C., & Hammock, B. (1998). Leukotoxin-diol produces greater acute lung injury in mice than does leukotoxin. FASEB Journal, 12(5). https://ucdavis.pure.elsevier.com/en/publications/leukotoxin-diol-produces-greater-acute-lung-injury-in-mice-than-d

What Prevents Us From Losing Weight?

One of the biggest failures of the diet and nutritional science worlds is the inability to help people lose weight and keep it off. 

"Treatment of obesity by reducing calorie intake, despite having a good success rate in promoting initial weight-loss, has a generally poor outcome for long-term weight control [7]." (McNay, 2013)

I recently came across McNay 2013, a fascinating study that looks at how this happens (in mice, but seems quite relevant!): "High fat diet causes rebound weight gain."

They used a fairly standard "high-fat diet" (HFD) to induce obesity in mice. The fats in the diet were lard and soybean oil, the usual suspects.

A very busy chart. From (McNay 2013)
Fig. 1 a and b. (AL = ad libitum)

What's interesting is that they then attempted to cure the obesity they had caused, using a variety of approaches: a high-carb diet (HCD), a high-protein diet (HPD), and a ketogenic diet (KD), and calorie restriction (CR)—a "diet" of the eat less variety.

CR worked best, regardless of the composition of the diet—they were under-eating by 30%, and that's easy to do to a mouse in a cage. However, this had a negative effect on the mice's brain.

The other diets also worked for weight reduction, in the order of KD best, then HCD, then HPD. The HFD mice stayed fat (Fig. 1a). For final weight of the mice allowed to eat to their heart's content, they KD also worked best, then the control, the HPD, the HCD, and the HFD was the worst (Fig. 1b).

The HFD also had a negative effect on the brains of the mice, regardless of how much they were eating. This effect also persisted to a small extent even when the mice were switched to one of the other, weight-loss-inducing diets.

However, once the CR mice were again allowed to eat as much as they pleased on their diets:

"As expected, all mice showed significant rebound weight gain after release from CR... However, rebound BW [body weight] was significantly different across treatment groups with obese mice treated with HFD-CR rebounding to a higher BW than controls.... Although DIO [diet-induced obesity] mice treated with non-HFD showed a trend towards higher  rebound BW than controls, this only reached statistical significance at a one point in the case of HCD.... Hence the failure to achieve long-term weight control following CR only occurred in obese mice fed HFD during CR, coinciding with the maintenance of altered hypothalamic remodelling."

So the damage to their brain from the HFD persisted even though weight-loss due to dieting (CR).

However, "The increase in rebound BW in DIO mice treated with HFD-CR was not permanent but resolved after 6 weeks of ad-lib chow re-feeding."

Now the HFD wasn't actually the high-fat diet, here, that's a bit of a misnomer. It was 45 % energy. The KD was 93.4 % energy from fat—that's a high-fat diet!

"It is of particular interest that the specific effect of moderately high fat diet  (HFD) to alter hypothalamic proliferative remodelling is not shared by ultra high fat ketogenic diet (KD)."

So fat alone isn't the problem. It's the combination of fat and carbohydrate, and a good dose in seed oils (provided here from lard and soybean oil), as has been shown in other studies. In other words, the diet we are told to eat by the dietary guidelines.

And the "eat less" advice we constantly hear doesn't work at all, unless you also change your diet.

"These data support the view that treating obesity with CR does not by itself cure obesity despite treating the overt symptom of increased BW."

(My colleague Peter at the Hyperlipid blog also had some thoughts on this paper.)

---

Dobromylskyj, P. (2021, May 19). Of mice and men (2) In the brain [Blog]. Hyperlipid. http://high-fat-nutrition.blogspot.com/2021/05/of-mice-and-men-2-in-brain.html

 
McNay, D. E. G., & Speakman, J. R. (2013). High fat diet causes rebound weight gain. Molecular Metabolism, 2(2), 103–108. https://doi.org/10.1016/j.molmet.2012.10.003

Interview: The Seed Oil/COVID-19 Connection—Discussing Leukotoxin on A Neighbor's Choice with David Gornoski

From last Friday, May 7th: discussing some follow-up data to this post from last year: 

Does Consumption of Omega-6 Seed Oils Worsen ARDS and COVID-19?

"David Gornoski is joined by nutritional researcher Tucker Goodrich. The two talk about camping as a break from modern excessiveness; the connection between linoleic acid and COVID; and more. Are people who are high in Omega-6 fatty acids more susceptible to COVID? What is ARDS? Should chicken consumption be decreased? Is butter bad for us as certain “studies” claim? Are peanut and palm oils good for us? Listen to the full episode to find out."

Here's the direct link, and here's the embedded player: 

Interview: "Tucker Goodrich Talks Seed Oils" with David Gornoski on A Neighbor's Choice

 I know, what a shocking topic!

"Nutritional researcher Tucker Goodrich returns to the show and joins David Gornoski in a fascinating conversation on the COVID effects on immunity, the validity of mask mandates, seed oils, and more. Should science be made subject to the whims and fancy of whoever that funds it? Is Fauci’s advice on virology unquestionable?"

Here's the direct link, and here's the embedded player: 

This is, by the way, a radio show released after the fact as a podcast. It's very cool to be getting some feedback from a mass audience.