"PORSCHE’S “INNODRIVE” CRUISE CONTROL “will throw the car into a blind corner at speeds you’d never d…"

Sounds fun!

Link via Instapundit

Podcast Ep 9: Dave Feldman, Citizen Scientist—What Causes Heart Disease

 

Trying something new, thanks to the many issues with Blogger, and Google, in general.

New posts are going to be at the Substack I have set up, I'll make a more complete notice once I figure it out a bit better.

First one is the shownotes for this podcast, and links to the files.

Ep 9: Dave Feldman, Citizen Scientist—What Causes Heart Disease

"Regulation of ferroptosis by lipid metabolism"

Ferroptosis = seed oil toxicity. "Sensitivity to ferroptosis is governed by the levels of peroxidizable polyunsaturated lipids..."

Link via scott dixon[Author]

"Associations between Plasma Lipid Mediators and Chronic Daily Headache Outcomes in Patients Randomized to a Low Linoleic Acid Diet with or without Added Omega-3 Fatty Acids"

Interesting follow-up to the headache research: Essential omega-3 fatty acids offer benefit to headache sufferers.

Link via Taha AY

"Enhancement of the liver's neuroprotective role ameliorates traumatic brain injury pathology"

That's a surprise! The liver dynamically produces brain-protective factors in response to injury.

Link via Hammock BD

"Calorie restriction and pravastatin administration during pregnancy in obese rhesus macaques modulates maternal and infant metabolism and infant brain and behavioral development"

"...negative impacts were also found in both mothers and infants. Our study emphasizes the importance of assessing gestational interventions for maternal obesity on both maternal and offspring long-term outcomes."

Link via Taha AY

"Neuroprotective effect of herbal extracts inhibiting soluble epoxide hydrolase (sEH) and cyclooxygenase (COX) against chemotherapy-induced cognitive impairment in mice"

Interesting. (The memory-preserving compound is known commercially as "Mentat". Heh.) "Chemotherapy-induced cognitive impairment (CICI) is a novel clinical condition characterized by memory, learning, and motor function deficits. Oxidative stress and inflammation are potential factors contributing to chemotherapy's adverse effects on the brain. Inhibition of soluble epoxide hydrolase (sEH) has been proven effective in neuroinflammation and reversal of memory impairment."

Link via Hammock BD

"The Education Department Helps Combat Woke Discrimination"

Medicine is going racist, apparently. Not good.

Link via RSSOpinion

"Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids"

Fascinating. MUFAs (oleic acid) improve fat beta-oxidation and longevity.

Link via scott dixon[Author]

"What Should I Eat?" A Call To Action: The Seedy App

One question I get continuously is about how and what to eat if you are trying to avoid seed oils.

While it seems simple at first, since vegetable oils of one type or another are in the vast majority of processed foods, this is not a simple question.

I once spent my lunch hour in the salad dressing aisle at Whole Foods, trying to figure out what to eat. I read every single label, and finally found one single dressing that listed olive oil as its sole fat ingredient—no other oil. Most 'cream' dressings are more soybean oil than dairy!

So it's certainly not as simple as question as it might seem at first.

People reducing their seed oil intake (starting with me!) have reported the following benefits:

• Lost weight.
• Reduced blood pressure.
• Reduced insulin resistance.
• Improvement of fatty liver disease.
• Resolution of auto-immune conditions.
• Reduced susceptibility to sunburn

Two of the people experiencing such benefits are Ashley and Dr. Brian Kerley . 

They have faced a similar conundrum, as they removed seed oils from their diets they experienced benefits to their health, but they encountered the same difficulty in finding seed-oil free foods, and as they started spreading the news, they started encountering more and more people with the same questions. (See our discussion on YouTube below.)

Ashley initially started going to supermarkets and doing what I had done, going through the aisles and reading the labels, but she was compiling lists that people could buy as PDFs. These were very popular, but not super-easy to use, and obviously don't scale well. This was part of their Seed Oil Rebellion.

Visit the Seed Oil Rebellion site.

A fellow with some experience in mobile apps reached out to Ashley and Brian with the idea of an app that folks could use while in the supermarket, and he had an alpha version fleshed out.

The initial version worked well as a proof-of-concept, and fulfilled some basic requirements, but getting it to the next step is going to require some more effort.

Why Is This Important?

1. We think this is the biggest health issue of our times. Just speaking about America, the vast majority of Americans (some studies find ~90%) are sick with some sort of "chronic disease" such as heart disease, certain types of cancer, obesity, diabetes, or an auto-immune condition. All of these diseases are related to linoleic acid from seed oil consumption in one way or another, according to the medical research.
   
2. Government-sponsored research shows clear health risks from seed oils. For instance, two of the most commonly-used oils, canola and soybean, contain alpha-linolenic acid, which converts to a carcinogen when heated, and is the only recognized cause for an increasing epidemic of lung-cancer in non-smoking women around the world. The similar omega-6 fat in all seed oils is linoleic acid, and it produces a similar chemical, which the U.S. National Toxicology Program found "could be expected" to be carcinogenic. They did this analysis in response to a request from the National Cancer Institute. It's a mystery why they didn't complete the research into potential carcinogenicity of a major food source in the U.S. These are only two of the many toxic compounds produced by cooking with and consuming seed oils.
3. Government agencies, influential non-government organizations, and other medical professionals nevertheless continue to recommend the consumption of seed oils. It's clear that any change in policy may take further decades to occur. Can we wait?
4. Consumer pressure can accomplish what governments will fail to attempt. Removal of trans-fats, for instance, began when corporations like Cargill and McDonalds recognized the hazards and responded to anticipated customer demand. This occurred long before the FDA was embarrassed into banning them. Cargill recommended a fat that would produce lower amounts of toxins, and while this was done for economic reasons, the outcome is the same: greater health benefits for consumers of McDonald's' products.
5. Increasing our individual health can cause a fundamental reshaping of the obesogenic food environment. But as more people are able to make this change, corporations will notice and will start to respond to the demand by producing better food options, and choosing healthier, more environmentally sound fat sources such as dairy, Zero Acre's Cultured Oil, and other low-linoleic.

What Should You Do?

If you would like to support or participate in the seed oil rebellion, please visit our Seedy web site and help us* get this project to the next phase of development, while helping transform the American and world food supply to a healthier direction.

Please Visit The Seedy App Website!

---

* Ashley, Brian, and I are all founding stockholders in Seedy App Inc.

Requiescat in pace Ray Peat

Dr. Ray Peat

Ray Peat, a legendary figure in nutrition science, died on Thanksgiving. We don't know any details beyond that single fact, but he will continue to have an impact for years.

I didn't agree with all of his positions, but his cautionary work about dietary PUFAs was trail-breaking, even though he didn't do the research. There's a huge role in science for people who actually read the papers and connect the dots, to get a coherent picture out of the rubbish bin that medical science all too often is. He did an impressive job of that.

He'll be missed.

Thanks to David Gornoski for reaching out to Dr. Peat and making these two podcasts happen, I was honored to have the chance to speak to him, and to have learned from him.

Interview: Ray Peat, with David Gornoski on A Neighbor's Choice

"My Big Fat Panel: How Seed Oils Cause Obesity" on A Neighbor's Choice with David Gornoski

David put together a retrospective of some of our discussions with Dr. Peat:

Peat's kind of a niche, but he's also kind of a genius.

— Tucker Goodrich (@TuckerGoodrich) August 10, 2017

Yep. Peat is a bit of a genius, as is Skulachev. Add @DrPhilMaffetone to the list of guys decades ahead of their time...

@PeatDon

— Tucker Goodrich (@TuckerGoodrich) January 1, 2019

"A Clue to Rheumatoid Arthritis"

Yeesh. Are there any known endogenous antigens that mimic bacterial infection? And that are *already* known to be involved in Rheumatoid Arthritis? Beuller... Beuller...

Link via AAAS: Keyword search for query

Here's the clue:

"Unsaturated aldehyde, 4-hydroxynonenal (HNE) alters the structural integrity of HSA with consequences in the immuno-pathology of rheumatoid arthritis"

Are Seed Oils Inflammatory?

 tl:dr; Yes. This deserves a longer post, and will get it at some point, but for now this will have to do.

Gil Carvalho, a vegan MD/PhD, has a video out titled "Are Seed Oils Inflammatory?! (The *Evidence* No One Shows)" which I have not watched, and will not watch.

Carvalho is a movement vegan, and as such is presumed to be dishonest, based on the experience of myself and others (detailed here, here, and here on this blog).

But this video he has done seems to be misleading people about this topic, which is the intent, of course.

As I pointed out on Twitter, even Harvard has come around on this topic. 

How can you identify a movement vegan? He's the last guy arguing that seed oils aren't a problem.

Even Harvard has come around.https://t.co/481Rhh1eZn

— Tucker Goodrich (@TuckerGoodrich) October 19, 2022

The only folks who are arguing that seed oils are NOT inflammatory are movement vegans, the flat-earthers of nutrition science.

Brad Marshall of Fire in a Bottle did watch the video, and did a nice analysis of the "misrepresentation" and "low-quality evidence" Carvahlo uses. Watch the whole thing. I did.

(Brad goes through a number of studies I was not aware of, and which I will need to follow up on. Really some excellent work by Brad here. We need to get Brad some white-board software!)

Brad also has a post on this: 

Seed Oil and Fryer Oil Reality Video. D6D.

There's not much left to discuss, but there was one point I didn't think Brad handled fully.

At the beginning of Brad's discussion of Carvalho's video talks about a strawman argument concerning arachidonic acid and inflammation. That rang a bell.

One thing about these movement vegans: they all recycle the same arguments. Walter Willett or Dariush Mozaffarian make some bogus point, and they all latch on to it and recycle it for years. 

So here's a rebuttal I made on this argument a while back. From Brad's video with Carvalho's excerpts, it appears to be the same misleading nonsense.

My conclusion to this section applies to Carvalho as well, even more, as he is a medical doctor.

All this evidence was available when he wrote that. One can only conclude he’s completely unaware of the evidence on this subject. Spreading misinformation about an important health topic like this is not helpful and may prevent many people from undertaking an intervention that could provide significant benefits, as in these migraine sufferers.

Inflammation

Finally, we start to get to some actual science, and some claims we can evaluate beyond “no evidence provided!”:

“Let’s start with inflammation. The putative mechanism with regard to inflammation is that the omega-6 linoleic acid [LA] acts as a precursor to arachidonic acid [AA]; AA acts a substrate to form eicosanoids, and the eicosanoids AA is used to form may be pro-inflammatory. Ergo, as the logic goes, increasing PUFA – particularly LA – increases inflammation.”

Well, that’s not the most logical starting point, as one generally doesn’t start in the middle of the story, and of course he doesn’t quote anyone actually saying this.  He continues:

“Except there is no evidence that either increasing or decreasing LA levels alters levels of AA in humans. A review of 36 human intervention studies [his link to (Rett & Whelan, 2011)] highlighted that neither increasing LA levels by up to 551%, or decreasing LA levels by 90%, altered concentrations of AA in plasma, serum, or red blood cells [erythrocytes], despite increasing LA intake resulting in increased membrane phospholipid LA content. Putative mechanism does not = biological effect. The following illustration helps to illustrate why:”

Image from (Flanagan 2020b) Red notation mine.

See diagram to right (provenance unknown, he does not list a reference, but as it does not represent what he describes it as representing—see D6D—it’s unlikely that he created it).

This is, believe it or not, a necessarily drastically over-simplified version of metabolism and inflammatory pathways in which n-6 is involved! It leaves out quite a few well-recognized inflammatory pathways, however.

As that image makes clear, there are many different pathways, not just the one Flanagan provides the studies for. (Yes, this begins to look like another strawman, but we’re not keeping track!)

So let’s start by looking backwards, from the most well-recognized and effective marker/mediator of inflammation, C-reactive protein (CRP) (Watson et al., 2019)—which is not in the image above. CRP isn’t just a marker, it’s an active player in the body’s immune system:

“...it can be said that CRP possesses the functionality of a host defense molecule against not only atherosclerosis but against all diseases caused by proteins when proteins behave like a pathogen or a toxic molecule, in a life cycle that begins as free CRP in circulation and ends in ligand-bound mCRP at sites of inflammation...” (Singh & Agrawal, 2019)

Oxidized LDL (oxLDL) is such a toxic molecule, and indeed one of the roles of CRP is to bind to oxLDL and help remove it:

Figure 1 from (Deleanu et al.,2016),
showing oxidation of n-6 fats in oxLDL.

"...CRP also binds to the PC moiety of oxidized phosphatidylcholine [PtC] present in OxLDL and apoptotic cells, where CRP triggers the early steps of the classical complement pathway..."

“In addition, CRP only bound to unsaturated PtC in proportion to their degree of oxidation and unsaturation (Fig. 2A) and did not bind to the saturated PtC even if exposed to the same oxidizing conditions (Fig. 2A)." (Chang et al., 2002)

We’ve known since the 1980s that what is oxidizing in LDL is n-6 fats, (Deleanu et al., 2016) and:

“The nature of the substrate for lipid peroxidation, mainly the polyunsaturated fatty acids in lipid esters and cholesterol, is a dominant influence in determining susceptibility. As noted by Esterbauer et al. (52), there is a vast excess of polyunsaturated fatty acids in LDL, in relationship to the content of natural, endogenous antioxidants. The importance of the fatty acid composition was impressively demonstrated by our recent studies of rabbits fed a diet high in linoleic acid (18:2) or in oleic acid (18:1) for a period of 10 wk. LDL isolated from the animals on oleic acid-rich diet were greatly enriched in oleate and low in linoleate. This LDL was remarkably resistant to oxidative modification, measured either by direct parameters of lipid peroxidation (i.e., TBARS and conjugated dienes) or by the indirect criterion of uptake by macrophages (53)….

“In a recent study, human volunteers were fed a similar oleic acid-rich diet. When their
LDL was tested for susceptibility to oxidative modification, it was reduced albeit to a lesser degree than that noted in the rabbit studies (54). These studies demonstrate the feasibility of dietary modification of LDL fatty acid content in order to reduce its susceptibility to modification.”  (Witztum & Steinberg, 1991)

Multiple studies have confirmed that dietary manipulation can alter the fatty-acid composition of LDL, and hence its susceptibility to oxidation (Abbey et al., 1993; Hargrove et al., 2001; Parthasarathy et al., 1990; Reaven et al.,1994; Spiteller & Spiteller, 2000).

Thus:

“In conclusion, our data show that Ox-LDL and hs-CRP levels correlate positively in ACS [acute coronary syndrome] patients, supporting the hypothesis that Ox-LDL and CRP may play a direct role in promoting the inflammatory component of atherosclerosis in these individuals.” (Zhang et al., 2012)

Table 4 from (Bemelmans et al., 2004) Image cropped to focus on CRP.

Notably, while CRP is a reaction to inflammation, oxLDL is a cause of inflammation, due to its oxidized, dietarily induced n-6 fats (Hao et al., 2015; Kennedy et al., 2011; Norris et al., 2011; Que et al., 2018; Shapira & Pinchasov, 2008; Stiekema et al., 2019; van der Valk Fleur M. etal., 2016; Witztum, 2002) and ad nauseum, if you are interested.

So where does this get us as to diet and inflammation? (Bemelmans et al., 2004) looked at the question directly:

“Because of the lower CRP level, the present results suggest that a six-fold increased ALA intake may have anti-inflammatory effects, when investigated against an LA-rich background diet.”

While (Su et al., 2017) performed a systematic review and meta-analysis of RCTs in humans and found:

“However, in subjects with greater increase in LA intake, LA tends to increase the blood concentration of CRP.”

Attribution for CRP and OxLDL images at end.

There are a number of caveats and conditions which are not discussed here, and a discussion of the scope of the inflammation induced via oxLDL is outside the need for a simple proof that it happens, QED.

So let’s go back to Flanagan. After introducing his little diagram above and his supporting studies, he states:

“This is where the buck just stops for the inflammation argument. There is no evidence that the putative mechanism is operative, nor that there is an inflammatory effect of dietary LA in actual Homo Sapiens.”

Well. Obviously that’s wrong.

Let’s discuss another pathway, demonstration of which is a little less involved than the above, although crucial, path from dietary LA to CRP. This pathway, unlike the rather more obvious one above, is in his diagram.

“Does inflammation have a role in migraine?”

“Migraine is a prevalent disorder, affecting 15.1% of the world’s population…. We propose that the increase in migraine frequency leading to chronic migraine involves neurogenic neuroinflammation, possibly entailing increased expression of cytokines via activation of protein kinases in neurons and glial cells of the trigeminovascular system.” (Edvinsson et al., 2019)

This hypothesis was tested, in an animal model of course (we will get to why an animal model) in 2020:

“In preclinical models, HODEs, EpOMEs and DiHOMEs have been observed to participate in numerous (patho)physiological processes during inflammatory pain including mechanical and thermal hyperalgesia [excess pain]… We demonstrate two 11-hydroxy-epoxides increased proportions of responsive TNs [trigeminal neurons] in a concentration-dependent fashion, similar to PGE2. Further investigation revealed that exposure produced Ca2+ responses with high potency, at μM range, comparable to well-known pain mediators, LA and 9-HODE (Patwardhan et al., 2010, 2009).” (Doolen et al., 2020)

Here’s Flanagan’s diagram again, this time with the emphasized terms above circled. (I also highlighted soluble epoxy hydrolase (sEH), as this will be mentioned later):

Incidentally, LA is a “well-known pain mediator”? Hmm…

Now, they’re using “our rodent friends” here because they already demonstrated that reducing dietary linoleic acid in humans (and increasing n-3) reduces headache/migraine pain. In science, when one notices an effect in humans, one attempts to find out via an animal model what the mechanism is (Flanagan would probably still find this “odd”):

“In this randomized trial, the combination of increasing dietary n-3 fatty acids with concurrent reduction in n-6 LA (the H3-L6 intervention) produced statistically significant, clinically relevant improvements in headache hours per day, severe headache days, and headache-related quality of life compared to baseline, and compared to the n-6-lowering (L6) intervention. Prior to the intervention, this chronic headache population averaged 23 headache days per month and 10 headache hours per day, despite using an average of 6 different headache-related medications per subject.” (Ramsden, Zamora, et al., 2013b)

Now, before one jumps to the conclusion that it was the n-3 fats that had the effect and not the n-6 lowering, let’s look at another study, (Pradalier et al., 2001). The title will suffice, I think: “Failure of omega-3 polyunsaturated fatty acids in prevention of migraine: a double-blind study versus placebo.”

(While it’s outside the scope of this discussion, it’s important to note that the n-3 and n-6 fats interact, via some of the pathways above, and that increasing n-3 can replace n-6 in tissue, provided you also lower n-6. That may explain these results.)

“We hypothesized that hyperactive metabolism of n-6 linoleic (n-6 LA) and arachidonic (n-6 AA) acids, and insufficient metabolism of n-3 eicosapentaenoic (n-3 EPA) and docosahexaenoic (n-3 DHA) acids, contribute to headache pathogenesis."

The success of (Ramsden, Zamora, et al., 2013b) has led to a further, much larger, test detailed in (Mann et al., 2018), which is ongoing.

One of the really interesting findings in the study was:

“As expected, the L6 intervention reduced erythrocyte n-6 LA and a number of its pronociceptive [pro-pain] derivatives compared to baseline. Unexpectedly, the L6 intervention also reduced a number of pronociceptive HETEs compared to baseline, despite no change in their precursor n-6 AA in erythrocytes.”

So what this tells us is that Flanagan’s argument, that since AA didn’t change in blood, there was no effect possible on inflammation, was wrong.

“Although biochemical effects were less pronounced compared to the H3-L6 group, this L6 intervention did significantly alter erythrocyte fatty acids and their bioactive derivatives in a manner that we hypothesized would reduce pain.”

AA quantity seems to be tightly regulated in serum. Those studies were correct. But there are many other studies showing that the downstream metabolites of AA, like these HETEs, are still affected by dietary LA. This has been demonstrated in many other conditions with inflammatory components, which are outside the scope of this discussion.

I highlighted sEH in Flanagan’s diagram, because it was discovered by Bruce D. Hammock (Kodani & Hammock, 2015), who recently said:

“Seventy-five percent, by weight, of the drugs sold in the world work on a single pathway called the arachidonic cascade, where arachidonic acid is converted by cyclooxygenase into prostaglandins, which are strongly pro-inflammatory.” (Rice, 2020)

That’s the pathway detailed in Flanagan’s diagram. Overstimulation of that pathway arguably, is our biggest health problem. Aspirin, for instance, prescribed for cardiovascular disease prevention, works on that pathway. Obviously, one of the most common uses for drugs like aspirin is headache.

Hammock further commented, in a recent podcast:

"So we've got... a very fine-tuned biochemical system and we've sort of thrown the monkey wrench into it by eating too much of a good thing with [linoleic acid]." (Gornoski, 2021)

What was it Flanagan said again?

“This is where the buck just stops for the inflammation argument. There is no evidence that the putative mechanism is operative, nor that there is an inflammatory effect of dietary LA in actual Homo Sapiens.”

All this evidence was available when he wrote that. One can only conclude he’s completely unaware of the evidence on this subject. Spreading misinformation about an important health topic like this is not helpful and may prevent many people from undertaking an intervention that could provide significant benefits, as in these migraine sufferers.

Here's the post this discussion on Inflammation is from:

Thoughts on 'Of Rats and Sidney Diet Heart...', Alan Flanagan's Post Defending Seed Oils

"Evidence of increased sequestration of pro-resolving lipid mediators within brain esterified lipid pools of multiple sclerosis patients"

Fascinating. "RESULTS: The concentration of 7 esterified pro-resolving fatty acid epoxides within neutral lipids were significantly higher by 126%-285% in postmortem prefrontal cortex of MS compared to control participants. The concentration of esterified linoleic acid-derived 9(10)-epoxy-octadecenoic acid, a pro-inflammatory epoxide, was higher by 206% in MS compared to controls. No significant changes were observed in free or phospholipid-bound oxylipins. "CONCLUSION: In MS, several pro-resolving lipid mediators are trapped within prefrontal cortex neutral lipids, potentially limiting their supply and availability in the free bioactive form. This may explain why inflammation resolution is impaired in MS patients."

Link via Taha AY

Should the FDA Exist? and Heart Disease Linked to Seed Oils—A Neighbor's Choice with David Gornoski

Nice Friday evening discussion. Thank you David!

"Should the FDA Exist? Tucker Goodrich: Heart Disease Linked to Seed Oils"

"David Gornoski is joined by Tucker Goodrich and the two comment on the CDC’s unscientific pushing of the vaccines; the legitimacy of the VAERS system; the legitimacy of the FDA and the CDC; EcoHealth Alliance receiving more grants; seed oil consumption and the rise of coronary heart disease; whether sugar contributes to cardiovascular disease; and more."

Visit A Neighbor's Choice website at https://aneighborschoice.com"

Radio, so no video this time. Podcast:

 

"Soluble Epoxide Hydrolase Is Associated with Postprandial Anxiety Decrease in Healthy Adult Women"

More evidence that metabolism of omega-6 fats (in this case through sEH plays a role in a wide variety of conditions.

Link via Hammock BD

"Synthesis, In Vitro Profiling, and In Vivo Evaluation of Benzohomoadamantane-Based Ureas for Visceral Pain: A New Indication for Soluble Epoxide Hydrolase Inhibitors"

"Overall, these results suggest painful bladder syndrome as a new possible indication for sEHI, opening a new range of applications for them in the visceral pain field."

Link via Hammock BD

"German Energy Apocalypse Update VI"

Another catastrophe birthed of human arrogance and ignorance. "The rising costs for electricity and gas will have dramatic consequences for industry. The energy crisis is a “total catastrophe” which could threaten the existence of the whole sector, says Julius Wagner, Head Manager of the German Hotel and Restaurant Association in Hessen. 'In comparison, the Corona crisis was a walk in the park.'"

Link via eugyppius: a plague chronicle

"Ether lipid deficiency disrupts lipid homeostasis leading to ferroptosis sensitivity"

Ferroptosis = omega-6 toxicity. Oleic acid is protective.

Link via scott dixon[Author]

"Anti-Inflammatory Activity of Soluble Epoxide Hydrolase Inhibitors Based on Selenoureas Bearing an Adamantane Moiety"

Link via Hammock BD