Monday, December 14, 2020

Bill Lands (aka William E.M. Lands, PhD) Resources on n-6 and n-3 PUFAs

Bill Lands is one of the titans in the field of human PUFA metabolism. As Wikipedia puts it: "...[he] is an American nutritional biochemist who is among the world's foremost authorities on essential fatty acids."

I don't call him "Bill" to be familiar, after he retired he switched from publishing as William E.M. to Bill.

Here's a select bibliography of interesting things he's written and done.

He's pretty fiery, so be sure to watch those video of his speech in (I think) 1999 at the NIH workshop, whence this quote:

It's in four parts, but it's well worth it. 

Or this:

"Fifty years later, I still cannot cite a definite mechanism or mediator by which saturated fat is shown to kill people." (Lands 2008)

Graff, G., Sacks, R. W., & Lands, W. E. M. (1983). Selective loss of mitochondrial genome can be caused by certain unsaturated fatty acids. Archives of Biochemistry and Biophysics, 224(1), 342–350.

Lands, B. (2008). A critique of paradoxes in current advice on dietary lipids. Progress in Lipid Research, 47(2), 77–106.
Lands, B. (2014). Historical perspectives on the impact of n-3 and n-6 nutrients on health. Progress in Lipid Research, 55, 17–29.
Lands, B. (2020, February 1). Essential Fatty Acids Home Page. EFA Education.
NIH. (1999a, April 7). 1 of 4—Dr William Lands on Cardiovascular Disease Omega-6.
NIH. (1999b, April 7). 2 of 4—Dr William Lands on Cardiovascular Disease Omega-6.
NIH. (1999c, April 7). 3 of 4—Dr William Lands on Cardiovascular Disease Omega-6.
NIH. (1999d, April 7). 4 of 4—Dr William Lands on Cardiovascular Disease Omega-6.
NIH. (1999e, April 7). Workshop on the Essentiality of Omega-6 and Omega-3 Fatty Acids.
Strandjord, S. E., Lands, B., & Hibbeln, J. R. (2018). Validation of an equation predicting highly unsaturated fatty acid (HUFA) compositions of human blood fractions from dietary intakes of both HUFAs and their precursors. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 136, 171–176.
Wikipedia. (2020). William E.M. Lands. In Wikipedia.

Friday, December 11, 2020

Podcast Interview: "Linoleic Acid- Interview with Tucker Goodrich" with Dr. Joseph Mercola

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
They did a transcript of the interview, also! (PDF, I'm impressed!)

For new visitors, here are a few of my key posts, some of which are mentioned in the interview.

Below are the extremely rough notes that Dr. Mercola and I worked off in the interview, including a bibliography.

Questions are welcome in the comments.

I'm on twitter here, and am active.

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”


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.

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.

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.

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.

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.

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.

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.

Goodrich, T. (2016, February 5). The Cause of Metabolic Syndrome: Excess Omega-6 Fats (Linoleic Acid) in Your Mitochondria. Yelling Stop.

Goodrich, T. (2018, June 28). What’s Worse—Carbs or Seed Oils? Understanding a High-PUFA Diet. Yelling Stop.

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.

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.

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.

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.

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.

Price, W. (1938). Nutrition and Physical Degeneration. A Project Gutenberg of Australia EBook.

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.

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.

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.

Stefansson, V. (1960). Cancer: Disease of Civilization?: An Anthropological and Historical Study. Hill and Wang.

Taubes, G. (2008). Good Calories, Bad Calories. Penguin RandomHouse.

Trowell, H. C., & Burkitt, D. P. (1981). Western Diseases, Their Emergence and Prevention. Harvard University Press.

Witztum, J. L., & Steinberg, D. (1991). Role of oxidized low density lipoprotein in atherogenesis. Journal of Clinical Investigation, 88(6), 1785–1792.

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.


Podcast Interview: Linoleic Acid- Interview Preview with Tucker Goodrich with Dr. Joseph Mercola

 This is coming up this weekend. Not sure how it will be available, but I'll post an update.

Podcast Interview: Tucker Goodrich on Vegetable Oils Being at the Heart of Modern Disease with Brian Sanders at Peak Human

File this under better late than never, it's from 2018. The show notes are pretty extensive, so I won't go over it here, please follow the link and show Brian some love.

What makes this interview special is that afterward, Joe Kalb decided to do a fact check of what I said (horrors!).

Vegetable Oils are Bad: Tucker Goodrich, Peak Human podcast review (Part 1)
The Peak Human podcast with host Brian Sanders and guest Tucker Goodrich is my favorite health podcast episode of 2018. In the podcast, Goodrich makes a persuasive case as to what he believes is the primary cause of the diseases of civilization (diabetes, coronary heart disease, autoimmune disease, cancer, etc). In this 94 minute podcast, he strongly posits that one type of food is at the root of the health problems of our times.

What is the primary cause of these health issues? Vegetable oils. Or seed oils, as they are more accurately but less commonly known.

These seed oils are industrially-processed oils containing high levels of Omega-6 fatty acids, which break down into toxic products in our bodies. These vegetable oils (corn oil, sunflower oil, canola oil, soybean oil, safflower oil, etc.) are cheap and therefore ubiquitous in our modern food supply. Tucker Goodrich postulates that these oils, even more than refined carbohydrates, are driving the diseases that plague most of the civilized world. 
Goodrich makes the case by looking at the effects of consuming vegetable oils from several valid perspectives. In my view, he approaches the modern disease problem from all the correct angles. Some of the perspectives from which he approaches the problem are...

Joe put a lot of work into this (an amazing amount of work!) as you can tell by the fact that he broke the work into three parts! 

"Vegetable Oils are Bad: Tucker Goodrich, Peak Human podcast takeaways (Part 2)"

Most of the fact-check is in this post: 

"Vegetable Oils are Bad: Tucker Goodrich, Peak Human listening companion (Part 3)"

 Thanks a lot to Brian for doing the interview, and for Joe for fact-checking me. 

I must confess I was terrified when I heard he had done this!

Brian has a movie coming out now, also. Food Lies, there's a trailer at the link!