Welcome to Dr. Mercola listeners and subscribers, if any of you make it here!
For existing readers, the Youtube version of this interview has been released. Here's the podcast version, on Apple Podcasts.
Here's Dr. Mercola's article on this topic:
How Linoleic Acid Wrecks Your Health
For new visitors, here are a few of my key posts, some of which are mentioned in the interview.
Why this is likely the major reason contributing to metabolic dysfunction and the epidemic of chronic disease
Criteria that I concluded had to be true for the cause (whatever it was) of chronic disease.
1. Trans-Species
This is a problem that we see in all human populations, and the animal species
that associate with them, which includes pets but also feral animals like rats,
pigeons, and racoons.
This eliminates genetic causes, and many pathogens, which do not cross species
lines easily.
2. Diet-based
Several crucial books (Price,
1938; Stefansson, 1960; Trowell & Burkitt, 1981) looked at healthy,
traditional cultures compared to sick ones, and made a clear suggestion that it
was diet based T&B made it clear that it affected diseases seemingly
unrelated to diet, like auto-immunity.
This eliminates other proposed mechanisms, like pollution (fattest country on
earth is in the South Pacific: what is the pollution?).
3. Novel
Must be a food that was recently introduced, contemporaneously with the
emerging pandemics of T2DM and obesity. (Taubes,
2008) looked at diabetes emergence in the 1800s, (Lee
et al., 1964) looked at emergence of ischaemic heart disease in the 20th
century vs traditional cultures.
4. Mechanistic
confirmation
Too easy to be fooled by epidemiology without some mechanistic
confirmation, as happened to Ancel Keys. (Ramsden
et al., 2016)
5. Contained
in D12492
This is the diet used to induce chronic diseases in lab animals. It seems
silly, but no-one went through this diet to figure out what ingredient actually
had the measured effect until 2012!
How you figured this out so early
Jen’s explanation (more complimentary): "Always open-minded and not biased as to what other people were believing and the trends. Simply were assessing evidence-based research and making decisions according to that."
My version: "Dumb luck and stubborn."
Had dramatic personal experience that couldn’t be explained by physicians, so looked into why it had happened. Stuck with exploration even when mentor in topic abandoned it.
Some seminal studies that provide irrefutable evidence of the hypothesis
“Irrefutable” is hard, if such a study had been done you wouldn’t be talking to me, this would be old news. Must follow Bill Lands, a pioneer in PUFA research, and “connect the dots”.
(Alvheim et al., 2012) shows what induces obesity, explains mechanism behind human-approved drug that treated multiple aspects of chronic diseases. Compare to D12492.
“Large randomized trials with rimonabant have demonstrated efficacy in treatment of overweight and obese individuals with weight loss significantly greater than a reduced calorie diet alone. In addition, multiple other cardiometabolic parameters were improved in the treatment groups including increased levels of [HDL], reduced triglycerides, reduced waist circumference, improved insulin sensitivity, decreased insulin levels, and in diabetic patients improvement in [HbA1c].” (Bronander & Bloch, 2007)
(Medina-Navarro et al., 2003) showing a physiological level of glucose and PUFA produced a poison in vitro. My tweet: “Etiology of metsym & chronic disease, in one chart. At physiologic lvls. God...”
(Singh et al., 2008) “Fat accumulation in Caenorhabditis elegans triggered by the electrophilic lipid peroxidation product 4-hydroxynonenal (4-HNE). Tweet: “N-6 metab 4-HNE induces obesity across species, "the process is conserved and thus likely to be universal."”
(Liu et al., 2011) “Formation Of 4-Hydroxynonenal From Cardiolipin Oxidation: Intramolecular Peroxyl Radical Addition And Decomposition”
(Witztum & Steinberg, 1991)
(Ghosh et al., 2004) “Brief episode of STZ-induced hyperglycemia produces cardiac abnormalities in rats fed a diet rich in n-6 PUFA” (Goodrich, 2018)
(Skulachev et al., 2009) “An attempt to prevent senescence: A mitochondrial approach”
(Bethancourt et al., 2019) “Household use of cooking oil increased and was positively associated with female BMI. Consumption of domesticated animal products did not change significantly but was positively associated with female BMI and male waist circumference. Conclusions Even small increases in energy-dense market-based foods can contribute to adiposity gains among a moderately active, subsistence-based population.”
(Maciejewska et al., 2015) “Following the six-month dietary intervention, hepatic steatosis resolved completely in all patients. This resulted in a significant decrease in the concentrations of all eicosanoids (LX4, 16-HETE, 13-HODE, 9-HODE, 15-HETE, 12-HETE, 5-oxoETE, 5-HETE) and key biochemical parameters (BMI, insulin, HOMA-IR, liver enzymes).”
(Goodrich, 2016) “The Cause of Metabolic Syndrome: Excess Omega-6 Fats (Linoleic Acid) in Your Mitochondria”
Will dive a bit into cardiolipin as I believe that is a major reason to explain the dilemma
Yes, covered in links above, plenty of material for discussion
Your best guess as to ideal LA consumption for optimal health and how to do that
LA is not essential, despite what was thought over last 90 years. Consumption should be minimal, discuss what should be avoided. (Alvheim et al., 2013; Blasbalg et al., 2011; Carlson et al., 2019)
Can tangent a bit to carnosine as a way to supply a sacrificial scavenger for reactive carbonyl species (RCS) or in LA context better known as OXLAMs or oxylipids
(Nègre-Salvayre et al., 2017) “A recent study
by Colzani and colleagues analyzed and compared the ability of several
classical carbonyl scavengers to prevent the carbonylation of proteins, and
concluded that carnosine is the most effective scavenger for HNE...”
(Zhao
et al., 2015) “Carnosic Acid as a Major Bioactive Component in Rosemary Extract
Ameliorates High-Fat-Diet-Induced Obesity and Metabolic Syndrome in Mice”
References
Alvheim, A. R., Malde, M. K., Osei‐Hyiaman, D., Hong, Y. H., Pawlosky, R. J., Madsen, L., Kristiansen, K., Frøyland, L., & Hibbeln, J. R. (2012). Dietary Linoleic Acid Elevates Endogenous 2-AG and Anandamide and Induces Obesity. Obesity, 20(10), 1984–1994. https://doi.org/10.1038/oby.2012.38
Alvheim, A. R., Torstensen, B. E., Lin, Y. H., Lillefosse, H. H., Lock, E.-J., Madsen, L., Hibbeln, J. R., & Malde, M. K. (2013). Dietary linoleic acid elevates endogenous 2-arachidonoylglycerol and anandamide in Atlantic salmon (Salmo salar L.) and mice, and induces weight gain and inflammation in mice. The British Journal of Nutrition, 109(8), 1508–1517. https://doi.org/10.1017/S0007114512003364
Bethancourt, H. J., Leonard, W. R., Tanner, S., Schultz, A. F., & Rosinger, A. Y. (2019). Longitudinal Changes in Measures of Body Fat and Diet Among Adult Tsimane’ Forager-Horticulturalists of Bolivia, 2002-2010. Obesity, 27(8), 1347–1359. https://doi.org/10.1002/oby.22556
Blasbalg, T. L., Hibbeln, J. R., Ramsden, C. E., Majchrzak, S. F., & Rawlings, R. R. (2011). Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. The American Journal of Clinical Nutrition, 93(5), 950–962. https://doi.org/10.3945/ajcn.110.006643
Bronander, K. A., & Bloch, M. J. (2007). Potential role of the endocannabinoid receptor antagonist rimonabant in the management of cardiometabolic risk: A narrative review of available data. Vascular Health and Risk Management, 3(2), 181–190. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994026/
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
Ghosh, S., Qi, D., An, D., Pulinilkunnil, T., Abrahani, A., Kuo, K.-H., Wambolt, R. B., Allard, M., Innis, S. M., & Rodrigues, B. (2004). Brief episode of STZ-induced hyperglycemia produces cardiac abnormalities in rats fed a diet rich in n-6 PUFA. American Journal of Physiology. Heart and Circulatory Physiology, 287(6), H2518-2527. https://doi.org/10.1152/ajpheart.00480.2004
Goodrich, T. (2016, February 5). The Cause of Metabolic Syndrome: Excess Omega-6 Fats (Linoleic Acid) in Your Mitochondria. Yelling Stop. http://yelling-stop.blogspot.com/2016/02/the-cause-of-metabolic-syndrome-excess.html
Goodrich, T. (2018, June 28). What’s Worse—Carbs or Seed Oils? Understanding a High-PUFA Diet. Yelling Stop. http://yelling-stop.blogspot.com/2018/06/whats-worsecarbs-or-seed-oils.html
Lee, K. T., Nail, R., Sherman, L. A., Milano, M., Lee, K. T., Deden, C., Imai, H., Goodale, F., Nam, S. C., Lee, K. T., Goodale, F., Scott, R. F., Snell, E. S., Lee, K. T., Daoud, A. S., Jarmolych, J., Jakovic, L., & Florentin, R. (1964). Geographic Pathology of Myocardial Infarction: Part I. Myocardial infarction in orientals and whites in the United States; Part II. Myocardial infarction in orientals in Korea and Japan; Part III. Myocardial infarction in Africans in Africa and negroes and whites in the United States; Part IV. Measurement of amount of coronary arteriosclerosis in Africans, Koreans, Japanese and New Yorkers. The American Journal of Cardiology, 13(1), 30–40. https://doi.org/10.1016/0002-9149(64)90219-X
Liu, W., Porter, N. A., Schneider, C., Brash, A. R., & Yin, H. (2011). Formation Of 4-Hydroxynonenal From Cardiolipin Oxidation: Intramolecular Peroxyl Radical Addition And Decomposition. Free Radical Biology & Medicine, 50(1), 166–178. https://doi.org/10.1016/j.freeradbiomed.2010.10.709
Maciejewska, D., Ossowski, P., Drozd, A., Ryterska, K., Jamioł-Milc, D., Banaszczak, M., Kaczorowska, M., Sabinicz, A., Raszeja-Wyszomirska, J., & Stachowska, E. (2015). Metabolites of arachidonic acid and linoleic acid in early stages of non-alcoholic fatty liver disease—A pilot study. Prostaglandins & Other Lipid Mediators, 121, 184–189. https://doi.org/10.1016/j.prostaglandins.2015.09.003
Medina-Navarro, R., Durán-Reyes, G., Díaz-Flores, M., Kumate Rodríguez, J., & Hicks, J. J. (2003). Glucose autoxidation produces acrolein from lipid peroxidation in vitro. Clinica Chimica Acta; International Journal of Clinical Chemistry, 337(1–2), 183–185. https://doi.org/10.1016/j.cccn.2003.07.005
Nègre-Salvayre, A., Garoby-Salom, S., Swiader, A., Rouahi, M., Pucelle, M., & Salvayre, R. (2017). Proatherogenic effects of 4-hydroxynonenal. Free Radical Biology and Medicine, 111, 127–139. https://doi.org/10.1016/j.freeradbiomed.2016.12.038
Price, W. (1938). Nutrition and Physical Degeneration. A Project Gutenberg of Australia EBook. http://gutenberg.net.au/ebooks02/0200251h.html
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Singh, S. P., Niemczyk, M., Zimniak, L., & Zimniak, P. (2008). Fat accumulation in Caenorhabditis elegans triggeredby the electrophilic lipid peroxidation product 4-Hydroxynonenal (4-HNE)—Full Text. Aging, 1(1), 68–80. https://doi.org/10.18632/aging.100005
Skulachev, V. P., Anisimov, V. N., Antonenko, Y. N., Bakeeva, L. E., Chernyak, B. V., Erichev, V. P., Filenko, O. F., Kalinina, N. I., Kapelko, V. I., Kolosova, N. G., Kopnin, B. P., Korshunova, G. A., Lichinitser, M. R., Obukhova, L. A., Pasyukova, E. G., Pisarenko, O. I., Roginsky, V. A., Ruuge, E. K., Senin, I. I., … Zorov, D. B. (2009). An attempt to prevent senescence: A mitochondrial approach. Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1787(5), 437–461. https://doi.org/10.1016/j.bbabio.2008.12.008
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Zhao, Y., Sedighi, R., Wang, P., Chen, H., Zhu, Y., & Sang, S. (2015). Carnosic Acid as a Major Bioactive Component in Rosemary Extract Ameliorates High-Fat-Diet-Induced Obesity and Metabolic Syndrome in Mice. Journal of Agricultural and Food Chemistry, 63(19), 4843–4852. https://doi.org/10.1021/acs.jafc.5b01246
