Wednesday, December 7, 2022

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:

Thursday, December 1, 2022

Thoughts on "Sugar on Your Coconut Oil?"

 Peter posted some interesting thoughts on obesity/NAFLD in a low-linoleic context. I posted the following as a comment over there, but wanted to surface it here. So read this first:

"Sugar on your coconut oil?"


Thanks for Parekh 1998, hadn't seen that one.

It raises a couple of thoughts.

Igarashi et al., 2015 (10.1016/j.bbalip.2015.05.006) found that sugar stimulated the endocannabinoid system, but to a less extent than LA, but via the same mechanism:

"Additionally, we report the unexpected finding that 7-day maintenance on a diet high in sucrose can also disable feeding-dependent OEA and LEA mobilization. The results suggest that FAE-mediated satiety signaling is suppressed by high fat or high sucrose in the diet, and that this suppression might contribute to hyperphagia and the development of obesity."

So if you have a high fat diet that's too low in LA, sucrose might substitute for it, in part.

Second, the other extra-mitochondrial LA obesity pathway is generation of the obesogen HNE, which of course only comes from LA and other n-6 fats. Cannizzaro et al., 2017 (10.1186/s12986-016-0149-z) measured the harm of a HFD (for maximal confusion, this is a High FRUCTOSE Diet):

“The level of HNE-modified proteins in plasma was increased almost 2-fold by HFD treatment, while RGZ completely normalized the level of HNE adducts (Fig. 6a).”

Which gets us back to Surwit. If you want to reduce the obesogenic effect of the Surwit diet, Chang et al., 2020 (10.21203/rs.3.rs-104384/v1) block the proliferation of HNE by stimulating the HNE detox pathway in the form of aldehyde dehydrogenase (ALDH):

“Importantly, the ALDH2 activator AD-9308 increased both the catalytic activity of WT and mutant enzyme, reduce serum 4-HNE levels, and effectively alleviated diet-induced obesity, fatty liver, insulin resistance, and glucose intolerance in both Aldh2-KI and WT mice in a dose-dependent manner.”

So sucrose/fructose is required to reduce the production of anti-obesogen OEA and stimulate production of obesogen HNE, in a low-LA environment?

The first and third of those posts are from my Obesity post.


Tuesday, November 8, 2022

How Seed Oils Make You Fat, with Tucker Goodrich and Jeff Nobbs—Fundamental Health with Dr. Paul Saladino


Another terrific discussion with Paul Saladino

"Today, Paul interviews Tucker Goodrich, Wall Street technology [exec] extraordinaire and independent researcher, and Jeff Nobbs, co-founder and CEO of Zero Acre Farms. They take a deep dive into the epidemic of seed oil consumption. They examine conflicting arguments, and then explain why seed oils are likely making humans fat, diabetic, and causing atherosclerosis."

Embedded video:


Podcast:


We discuss these two posts on Zero Acre's website:

"How Vegetable Oils Make Us Fat"

"Seed Oils as a Driver of Heart Disease"

Jeff has retained me as a paid consultant to Zero Acre to help him and his team develop content like this to spread the news about the health issues with industrial seed oils. As such, I thought it was important, when Paul reached out to me initially, to include Jeff. 

He's the real deal, he's doing this because he understands it and believes in it, and he and the Zero Acre team want to make sure we get the science right.

It's an excellent discussion, I think. Enjoy!

Monday, November 7, 2022

"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:

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. 

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: 


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 2020bRed 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., 1993Hargrove et al., 2001Parthasarathy et al., 1990Reaven et al.,1994Spiteller & 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., 2015Kennedy et al., 2011Norris et al., 2011Que et al., 2018Shapira & Pinchasov, 2008Stiekema et al., 2019van der Valk Fleur M. etal., 2016Witztum, 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, HODEsEpOMEs 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

Wednesday, November 2, 2022

"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

Tuesday, November 1, 2022

The Bitter Truth About Seed Oils, Inflammation, and Disease—The Genius Life with Max Lugavere


A really fun interview with a guy who has definitely done his homework.

"What you'll learn from this episode:

    • "How 89% of Americans are metabolically unhealthy, and even our pets have a 60% rate of obesity.
    • "What is the Israeli paradox, and why has India developed more metabolic health disorders since more people have switched from ghee to seed oils?
    • "Why seed oils are inflammatory—and how they affect your LDl, including the difference between oxidized LDL and non-oxidized LDL.
    • "What is a VLDL test, and how can this (often uncovered) test help you understand your real risk factor for atherosclerosis?
    • "The false dichotomy of seed oils vs. saturated fat—and the alternative, anti-inflammatory options: extra virgin olive oil and avocado oil.
"And so much more!


We covered a lot of topics, but heart disease was definitely a big one. 

I've already had a request for some of the references behind that discussion, if you are interested in more I suggest reading this post I co-authored over at Zero Acre:

"Seed Oils as a Driver of Heart Disease"

From that article: 

"Highlights

  • "The United States saw a catastrophic rise in heart disease during the mid-20th century most likely related to changes in dietary linoleic acid intake.
  • "Researchers found a significant disparity in the incidence and prevalence of heart disease, with cultures eating pre-industrial diets having extremely low incidence, if any, compared to populations eating industrialized diets.
  • "Before any human trials had been conducted, leading public health organizations assumed that lowering serum cholesterol levels and increasing seed oil consumption would lead to better health outcomes.
  • "In the United States, steadily rising seed oil consumption drove linoleic acid intake up from 2% of calories in the early 1900s to around 8.9-9.4% by 2010.
  • "By the late 20th century, research had revealed that the susceptibility of LDL particles to oxidation was a much better predictor of heart disease than changes in total cholesterol or LDL cholesterol levels.
  • "Numerous human clinical trials demonstrate that, like smoking, increased seed oil consumption increases LDL’s susceptibility to oxidation, posing a major concern when it comes to cardiovascular disease.
  • "Like smoking, seed oil consumption also induces oxidative stress, induces insulin resistance, damages the arterial endothelial wall, and increases oxidized LDL – a common mechanism that causes heart disease."

And if you are wondering, this is the puppy.


Friday, October 21, 2022

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!

"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:
 

Do Seed Oils Cause Heart Disease?

tl:dr—Seed oils are associated, and probably causal, in cardiovascular disease.

"Figure 3. Mendelian randomization analysis. A significant deviation from zero of the estimate of causal effect using all SNPs (solid red line) suggests a causal relationship between the metabolite and CHD." (Ganna et al., 2014)

Oh dear. So sorry... *

"The Mendelian randomization analysis... suggested a weak, but positive causal effect of MG 18:2 on CHD risk (odds ratio, 1.05... per SD increment in MG 18:2; P-value = 0.05) and a lack of causal effect for LysoPC 18:1, 18:2 and SM 28:1."

Even worse:

"...In the multivariable analysis for association with CHD, we separately included two covariates in addition to the main cardiovascular risk factors: [CRP] and statin treatment. The associations between the four metabolites and incident CHD were essentially the same...

"Lysophosphatidylcholines were negatively associated with BMI, markers of inflammations and subclinical cardiovascular disease, while a reverse pattern was observed for MG 18:2."

“We found evidences [sic] for a causal effect of MG 18:2 on CHD independently of triglycerides levels."

And: "We observed a strong positive association between MG 18:2 and CHD."

So what are they saying? A few terms, so you can understand the jargon:

  • Mendellian randomization is a way of correlating observational (epidemiological) data cross-referenced to genetic data. This is supposed to establish “causation” using epidemiology. **
  • MG 18:2 is monoglyceride linoleic acid (LA, chemical symbol C18:2). Linoleic acid attached to a glycerol molecule, in other words.
    LA is the most common fat found in seed oils. Fats are generally consumed as either triglycerides or phospholipids, in this case two fats have been removed from a tri-glyceride, leaving one, a mono-glyceride.
  • CHD is coronary heart disease.
  • CRP is c-reactive protein, part of the body’s inflammatory response, and used as a marker of inflammation.
  • Phosphatidylcholines (PC) are a way of packaging fats, used extensively in the body’s cellular membranes. Tri-, di-, or mono-glycerides attach three, two, or one fat(s) to a glyceride backbone, here two fats are attached to a choline backbone. You’ve heard of lecithin? This is the chemical name for lecithin.
  • Lysophosphatidylcholine (LysoPC) is a PC from which one fat has been removed.

So they looked at metabolites of various things in the body (Metabolomics) and found a correlation between a form of linoleic acid (LA) and heart disease. LA is generally found in triglycerides (TG), but here they found the association with TG was weaker than that of LA with heart disease. TG is an established risk factor for heart disease.

Moreover they found that this effect became stronger as the amount of LA increased: “a weak, but positive causal effect of MG 18:2 on CHD risk (odds ratio, 1.05... per SD [standard deviation] increment in MG 18:2…” This is known as a dose-response, and suggests that causation is present (criteria 5 in the Bradford Hill list of criteria for determining possible causation from observed data).

More:

"Several observations suggest an involvement of MG 18:2 in the pathogenesis of CHD. First, MG 18:2 is central in the synthesis and breakdown of triglycerides and a causal effect of plasma triglyceride levels on CHD risk have recently been supported by a large Mendelian randomization analysis [11]. Although highly correlated, when both MG 18:2 and triglycerides were included in the same model, both showed independent significant associations with CHD. Moreover, when separately added to a model with main cardiovascular risk factors, MG 18:2 was a better predictor of CHD than triglycerides. Second, MG 18:2 was associated with higher levels of cardiovascular risk factors and markers of subclinical CVD and oxidative stress. Third, Mendelian randomization analysis suggested a weak, but positive causal effect of MG 18:2 on CHD risk. Several SNPs reported for association with CHD remained associated with MG 18:2 (in the PCSK9, HHIPL1, PLG, ApoE/ApoC1, COL4A1/COL4A2 regions, P-values,0.05), even after adj. for main cardiovascular risk factors.”

"Our study has several strengths. To our knowledge, this is the largest study investigating the metabolome in relation to incident CHD."

"In conclusion, in the largest study of the metabolome in relation to incident CHD to date, we identified [LysoPC]s 18:1, 18:2, monoglyceride 18:2 and sphingomyelin 28:1 as risk factors of coronary heart disease and suggested a causal effect for monoglyceride 18:2 on CHD."

So much for the claims there’s no epidemiology supporting the hypothesis that LA from seed oils is causal in heart disease.

"Large-scale metabolomic profiling identifies novel biomarkers for incident coronary heart disease" (Ganna et al., 2014)

Of course linoleic acid is hardly "novel"... The link between LA and heart disease goes all the way back to the 1950s:

“Our results are in accord with the recent work of [(Böttcher et al., 1960)] who showed conclusively that human atherosclerotic plaques have a high content of linoleic acid which increases with the severity of the disease….

“This result would support the view that linoleic acid is essential for the production of atherosclerotic plaques.” (Gresham & Howard, 1961)

If you want more information on the link between seed oil and heart disease, see our work here (Zero Acre Editorial Team, 2022)

I discussed with Prof. Tom Brenna the importance of choline and phospholipids in the metabolism of fat in the body (Goodrich,2022), and I find it very interesting that the correlations between LA in phospholipid form (LysoPC 18:2) and triglyceride form (MG 18:2) is different. Monoglycerides can have very distinct effects on the body (Poursharifiet al., 2017), this may be such a case.

So what's the most messed up thing about this analysis?

They never mention the word "linoleic," or any part of it.

I found this while pulling threads, I never would have found it looking for any useful search term.

* Came across this paper today, while working on something concerning diabetes (Al-Sariet al., 2021). Really, you shouldn’t have to dig into something like this (ChEBITeam, 2018) to find a pretty important paper, but the Tower of Babel story is true in every important way, except perhaps for not actually having happened.

** I have some serious issues with MR, which I will not go into here, but since I have been told that there is no evidence using MR that LA causes CVD, I found this satisfying.

References

Al-Sari, N., Schmidt, S., Suvitaival, T., Kim, M., Trošt, K., Ranjan, A. G., Christensen, M. B., Overgaard, A. J., Pociot, F., Nørgaard, K., & Legido-Quigley, C. (2021). Changes in the lipidome in type 1 diabetes following low carbohydrate diet: Post-hoc analysis of a randomized crossover trial. Endocrinology, Diabetes & Metabolism, 4(2), e00213. https://doi.org/10.1002/edm2.213

Böttcher, C. J. F., Woodford, F. P., Romeny-Wachter, C. C. T., Houte, E. B., & Gent, C. M. V. (1960). Fatty-Acid Distribution In Lipids Of The Aortic Wall. The Lancet, 275(7139), 1378–1383. https://doi.org/10.1016/S0140-6736(60)91153-3

ChEBI Team. (2018). Phosphatidylcholine 35:4 (CHEBI:91322) [Informational]. European Molecular Biology Laboratory; Chemical Entities of Biological Interest. https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:91322#25502724

Ganna, A., Salihovic, S., Sundström, J., Broeckling, C. D., Hedman, A. K., Magnusson, P. K. E., Pedersen, N. L., Larsson, A., Siegbahn, A., Zilmer, M., Prenni, J., Arnlöv, J., Lind, L., Fall, T., & Ingelsson, E. (2014). Large-scale metabolomic profiling identifies novel biomarkers for incident coronary heart disease. PLoS Genetics, 10(12), e1004801. https://doi.org/10.1371/journal.pgen.1004801

Goodrich, T. D. (2022, September 1). Podcast Ep. 5: Prof. Tom Brenna on Omega-3 and Omega-6 in Human Health—with Dr Brian Kerley [Blog]. Yelling Stop. http://yelling-stop.blogspot.com/2022/09/podcast-ep-5-prof-tom-brenna-on-omega-3.html

Gresham, G. A., & Howard, A. N. (1961). The Effect of Dietary Fats and Synthetic Glycerides on the Production of Atherosclerosis and Thrombosis in the Rat. British Journal of Experimental Pathology, 42(2), 166–170. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2082415/

Poursharifi, P., Madiraju, S. R. M., & Prentki, M. (2017). Monoacylglycerol signalling and ABHD6 in health and disease. Diabetes, Obesity & Metabolism, 19 Suppl 1, 76–89. https://doi.org/10.1111/dom.13008

Zero Acre Editorial Team. (2022, August 12). Seed Oils as a Driver of Heart Disease [Advertisement]. Zero Acre. https://www.zeroacre.com//white-papers/seed-oils-as-a-driver-of-heart-disease

 

Friday, October 14, 2022

"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

Thursday, October 13, 2022

"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

Saturday, October 8, 2022

"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

Sunday, October 2, 2022

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

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

Link via scott dixon[Author]

Thursday, September 8, 2022

Podcast Ep. 6: Dr. Joshua Durham; Family Doc Gets Red-pilled by Seed Oils—with Dr. Brian Kerley

Dr. Durham is a Family Physician in Boise, Idaho; and is my doctor.


I think this is a great podcast. I really do believe that if we are going to fix our diet problem, we're going to do it one anecdote at a time.

Dr. Durham shares his own story of how, a former athlete, he found himself fat and ill at 38 years old.

And we discuss how this has changed his practice of medicine, since he now has his own success story to tell to his patients.

He also shares some of his patient success stories, and the challenges with getting people to fix their diets.

YouTube:

Rumble:

Podcast:


Show notes:

Joshua Durham, DO

·        https://www.saintalphonsus.org/provider/joshua-durham

Blog comment:

Dr. Durham: “If you need a family Dr. here in Boise hit me up. I went from 235lbs to keto to carnivore and then finally came across your info. Now at 195 I feel comfortable knowing what I can and can't have and why I was so sick. Felt great on carnivore but can't live that way forever. Thank you for your work.”

·        http://yelling-stop.blogspot.com/2021/04/experts-do-as-we-say-not-as-we-do.html?showComment=1620609617154#c416429453974276542

“Doctor of Osteopathy vs. Medical Doctor- What are the Differences?”

·        https://hecec.human.cornell.edu/2016/02/12/doctor-of-osteopathy-vs-medical-doctor-what-are-the-differences/

Dr. Eric Westman

·        https://ericwestmanmd.com/

New Atkins for a New You: The Ultimate Diet for Shedding Weight and Feeling Great by Eric C. Westman, Stephen D. Phinney, Jeff S. Volek

·        https://amzn.to/3qd9fzy (this link benefits the podcast!)

Dr. Durham: “Good fat/bad fat” I wrote a post about this: “Good Keto vs. Bad Keto

·        http://yelling-stop.blogspot.com/2021/09/good-keto-vs-bad-keto.html

Dr. Durham: “Then I saw your interview with Paul Saladino…”

·        “How Seed Oils Destroy Your Mitochondria and Lead To Chronic Disease, with Tucker Goodrich” https://carnivoremd.com/how-seed-oils-destroy-your-mitochondria-and-lead-to-chronic-disease-with-tucker-goodrich/

“…and then I watched Brad Marshall…”

·        Brad’s blog is here: https://fireinabottle.net/

Drs. Kerley and Durham compare “elevator pitches” to patients.

Dr. Durham: “I needed 4 pills based on the guidelines, and I was 38 years old.”

Tucker: “Lean-Mass Hyper Responder”:
Norwitz, N. G., Soto-Mota, A., Kaplan, B., Ludwig, D. S., Budoff, M., Kontush, A., & Feldman, D. (2022). The Lipid Energy Model: Reimagining Lipoprotein Function in the Context of Carbohydrate-Restricted Diets. Metabolites, 12(5), 460. https://doi.org/10.3390/metabo12050460

Dr. Durham: 40:02 “American College of Cardiology article…”
Astrup, A., Magkos, F., Bier, D. M., Brenna, J. T., de Oliveira Otto, M. C., Hill, J. O., King, J. C., Mente, A., Ordovas, J. M., Volek, J. S., Yusuf, S., & Krauss, R. M. (2020). Saturated Fats and Health: A Reassessment and Proposal for Food-based Recommendations: JACC State-of -the-Art Review. Journal of the American College of Cardiology, 76(7), 844–857. https://doi.org/10.1016/j.jacc.2020.05.077
See Episode 5, in which we interview Tom Brenna, one of the co-authors of that article: https://www.youtube.com/watch?v=rrQ8q_ctGUQ

Tucker: “The AGEs, same thing—Chris Masterjohn did a great post years ago looking into it:
Masterjohn, C. (2011, October 7). Where Do Most AGEs Come From? O Glycation, How Thy Name Hast Deceived Me! | [Blog]. Chris Masterjohn, PhD. https://chrismasterjohnphd.com/blog/2011/10/07/where-do-most-ages-come-from-o

Tucker: “Polyunsaturated fats are about 10x as effective in producing advanced glycation end products [than glucose]…”
Fu, M.-X., Requena, J. R., Jenkins, A. J., Lyons, T. J., Baynes, J. W., & Thorpe, S. R. (1996). The Advanced Glycation End Product, N-(Carboxymethyl)lysine, Is a Product of both Lipid Peroxidation and Glycoxidation Reactions. Journal of Biological Chemistry, 271(17), 9982–9986. https://doi.org/10.1074/jbc.271.17.9982

Tucker: Lp(a):

·        Hazard ratio 16.8: Tsimikas, S., Brilakis, E. S., Miller, E. R., McConnell, J. P., Lennon, R. J., Kornman, K. S., Witztum, J. L., & Berger, P. B. (2005). Oxidized Phospholipids, Lp(a) Lipoprotein, and Coronary Artery Disease. New England Journal of Medicine, 353(1), 46–57. https://doi.org/10.1056/NEJMoa043175

·        Hazard ratio 1 in Africa: Paré, G., Çaku, A., McQueen, M., Anand, S. S., Enas, E., Clarke, R., Boffa, M. B., Koschinsky, M., Wang, X., Yusuf, S., & null,  null. (2019). Lipoprotein(a) Levels and the Risk of Myocardial Infarction Among 7 Ethnic Groups. Circulation, 139(12), 1472–1482. https://doi.org/10.1161/CIRCULATIONAHA.118.034311

·        2 sure-fire ways to raise Lp(a):
1. Statins: Yeang, C., Hung, M.-Y., Byun, Y.-S., Clopton, P., Yang, X., Witztum, J. L., & Tsimikas, S. (2016). Effect of therapeutic interventions on oxidized phospholipids on apolipoprotein B100 and lipoprotein(a). Journal of Clinical Lipidology, 10(3), 594–603. https://doi.org/10.1016/j.jacl.2016.01.005
2. Healthy diet: Navab Mohamad, Reddy Srinivasa T., Van Lenten Brian J., & Fogelman Alan M. (2004). Apparent Paradox of Low-Fat “Healthy” Diets Increasing Plasma Levels of Oxidized Low-Density Lipoprotein and Lipoprotein(a). Arteriosclerosis, Thrombosis, and Vascular Biology, 24(3), 392–393. https://doi.org/10.1161/01.ATV.0000118014.49565.fc

·        Pork and LDL: Stewart, J. W., Kaplan, M. L., & Beitz, D. C. (2001). Pork with a high content of polyunsaturated fatty acids lowers LDL cholesterol in women. The American Journal of Clinical Nutrition, 74(2), 179–187. https://doi.org/10.1093/ajcn/74.2.179

Treating Lp(a)/OxLDL with antibodies: https://www.oxitopepharma.com/approach

Dr. Kerley: Robb Wolf interview: https://www.youtube.com/watch?v=Lku8kJdHOqY

Wooden breast in chickens:
Soglia, F., Mudalal, S., Babini, E., Di Nunzio, M., Mazzoni, M., Sirri, F., Cavani, C., & Petracci, M. (2016). Histology, composition, and quality traits of chicken Pectoralis major muscle affected by wooden breast abnormality. Poultry Science, 95(3), 651–659. https://doi.org/10.3382/ps/pev353

“Dr. Mark Cucuzzella – A Doctor’s Perspective On Treating Diabetes” https://robbwolf.com/2016/07/26/episode-329-dr-mark-cucuzzella-a-doctors-perspective-on-treating-diabetes/

 

Thursday, September 1, 2022

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

This is a special episode, which Brian and I are very excited for.


Prof. Brenna is a leading researcher on polyunsaturated fats in child nutrition, who has done both animal and human work demonstrating the importance of a low-linoleic, high DHA diet for human health. 

In addition to his academic credentials linked below, he also served on the 2015 Dietary Guidelines Advisory Committee, and on the most recent FAO/WHO Expert Panel on Fats and Fatty Acids, so he's had a real impact on the world dietary recommendations. See the show notes below for more background, and the papers we discussed.

I hadn't spoken to Prof. Brenna prior to this interview, although I had listened to a presentation he made for the International Society for the Study of Fats and Lipids (ISSFAL) of which he is a past president, so I knew he was engaging and quotable. He didn't disappoint.

What I was surprised by was how he made many of the same points about the issues with seed oils that I make, unsolicited by me. 

It was a great discussion.

Post transitioned to Substack. Please click the link to read there and subscribe!

Tuesday, August 9, 2022

Interview: Brad Marshall, Tucker Goodrich on Obesity Causes, Reductive Stress—A Neighbor's Choice with David Gornoski

Brad Marshall, David, and my dog get together to talk about our commonalities and where we differ.

(That yipping you hear in the background is my new puppy. Sorry about that.)

"David Gornoski, Brad Marshall, and Tucker Goodrich get together for an investigative conversation on what exactly is causing the obesity crisis in modern society. What do we make of the idea of stearic acid as dietary fiber? Is reductive stress driving the obesity crisis? Do we get in a state of torpor after consuming linoleic acid? Is more sugar the way to go, as Dr. Ray Peat suggests?

Check out Brad Marshall's blog Fire in a Bottle here: https://fireinabottle.net
Visit A Neighbor's Choice website at https://aneighborschoice.com"

Podcast:

Tuesday, July 26, 2022

Cultured Oil, Zero Acres’ Answer to Seed Oils; Interview of Jeff Nobbs on A Neighbor's Choice with David Gornoski

Zero Acre launched their product today. See their website and their blog for lots of information. 

I think these two graphics, from their article "Cultured Oil Health Report" really get to why this is going to be a game-changer.

"How cooking oils turn toxic" shows how superior a low-linoleic acid oil like Cultured Oil is to the alternatives we've been told to use.

It's a game changer, especially for stir frying or sauteing which is a major cause of lung cancer.


And "Susceptibility to oxidation" shows how Cultured Oil is superior to all but the most traditional animal fats. (It's better than lard or duck fat since both those animals are fed high-grain & seed oils diets currently. Fix the feed, and they become a better option.)



What's the reason for this superior performance? It's obvious. "Linoleic acid content of liquid oils" shows Cultured Oil has the lowest linoleic acid content of any available liquid oil, comparable to only coconut oil, which has it's own oxidation issues due to the short-chain fats that comprise that oil.



David Gornoski and I interviewed Jeff Nobbs, the founder of Zero Acre a little while back, and had a great talk about the new product.

"In this special nutrition science podcast, David Gornoski and Tucker Goodrich are joined by Jeff Nobbs, co-founder of Zero Acre Farms. The discussion starts off with the realization that seed oils are harmful to our health. Jeff Nobbs and Tucker Goodrich also explain the mission of Zero Acre Farms, the development of cultured/fermented oil, whether cultured oil will be safe for consumption, whether we can feed the world with existing fats, and more."