🧵🧵🧵

The meta-analysis below is often considered strong evidence that dietary linoleic acid from seed oils does not affect inflammation.

It is a meta-analysis after all, looking at results across many clinical trials, sitting near the top of the "hierarchy of evidence" in biomedicine.

But... instead of taking its results at face-value, what do you find if peek under the hood, and take a look at the underlying trials themselves?

The main conclusion of the meta-analysis is: "increasing dietary LA [linoleic acid] intake does not have a significant effect on the blood concentrations of inflammatory markers."

Despite that main conclusion, the meta-regression they performed found a positive association between the change in linoleic acid intake and inflammatory marker CRP.

But I wouldn't take any of those things to the bank, because....

When you look into the individual RCTs cited, you find wildly different patient populations, study designs, experimental manipulations of dietary fats, durations, etc.

Some are not double-blind. Some are funded by corporations like Unilever.

The variability in design and patient populations is astounding, ranging from obese women who may also be smokers to dyslipidemic men or healthy patients, all varying in wildly in average age, from different parts of the world.

Some of the RCTs don't actually manipulate linoleic acid intake across a dose range, but give supplemental omega-3 PUFAs in the form of flax oil or fish oil, with something like corn oil as a placebo. Trials differ in the specific oils used, doses, etc.

The full table of clinical trials can be seen in the last image of this post.

Below in this thread are descriptions of the first three trials I looked at, which were simply the first three listed that lasted 12 weeks or longer.

This is meant to give a basic sense for the variance across trials.

1/5

This trial looked at women is abdominal obesity. Half used coconut oil and half used soybean oil, supplemented for 12 weeks and instructed to eat a hypocaloric diet.

The result used in the meta-analysis was changes in CRP.

CRP did NOT significantly change for the soybean oil group or the coconut oil group. It barely budged for SO, but dropped for CO... although the two groups differed at *baseline* for CRP, so 🤷‍♂️🤷‍♂️🤷‍♂️

As usual for many diet studies, the dietary data collections are pretty absurd: "a 24 h dietary recall was applied to subjects for a 3 day period (1 day of which was during a weekend) immediately before and 12 weeks after dietary intervention."

Another weird observation: omega-6s are supposed to decrease total and LDL cholesterol, while saturated fat is supposed to increase LDL.

But...

The soybean oil (seed oil) group saw an INCREASE in total cholesterol, LDL, and LDL:HDL, with a drop in HDL.

Is this a good trial? Should be included as evidence, one way or the other, on whether seed oils (ω-6 PUFAs) affect inflammation in the general population?

Next trial...

2/5

How has dietary fat consumption, especially as it relates to animal fat, changed over time?

Thanksgiving 🧵

🦃

1/ All of the information snippets in this thread come from this article (link in bio), which goes into much more detail.

2/

🧵A basic summary of this new lipidomics paper linking colon cancer to an imbalance between pro-inflammatory & pro-resolving processes, with a potential connection to seed oils.

More details in an upcoming podcast...

1/

https://twitter.com/trikomes/status/1866931314743709934

The paper references Virchow, who originally proposed that cancer represents a chronically inflamed, poorly healing wound.

🤔

2/

Here's what I'm reading ahead of my conversation with @garytaubes tomorrow.

We will be discussing the causes of obesity, including a compare/contrast of the major scientific models that are out there (e.g. energy balance, carbohydrate-insulin, etc.).

https://twitter.com/trikomes/status/1831775669979902003

Two views of how obesity arises:

Energy balance:
"obesity is often associated with excessive appetite and food intake. This currently prevailing view holds that excessive fat accumula- tion results because energy intake exceeds energy expenditure.1,2 Excessive food consumption is now considered the primary cause of the imbalance."

vs.

Fuel partitioning:
"individuals appear to accumulate and sustain excessive adiposity even with restricted food intake. This view attributes the fundamental cause of obesity to intrinsic metabolic defects that shift fuel partitioning from pathways for mobilization and oxidation to those for synthesis and storage."

Fastest downloaded episodes of the podcast so far this year:

#1
"DMT, Serotonin, Inflammation, Psychedelics, and Past, Present & Future of Psychedelic Medicine" with David Nichols & @lab_nichols #2
"Gut-Brain Communication, Vagus Nerve, Fats & Sugars, Food Addiction, Gut Hormones & Weight Loss Drugs" with Will de Lartigue

🧵#ScienceBreakdown: "Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors"

Interesting new paper by @DEOlsonLab, @LinTianPhD, et al. looking at why some serotonin 2A receptor agonists promote neuroplasticity, but others do not.

1/ Various small molecules, from endogenous neurotransmitters like serotonin to tryptamine #psychedelics, activate 5HT2A receptors... and yet they can lead to very different effects.

Getting at why this is was one of the basic motivations for this study.

2/

🧵I've done several episodes about #COVID, including the origins of the #SARSCoV2, the biological & epidemiology of the virus, and how mRNA vaccines work.

Here are a few good ones, and a long-from article, that focus on these topics:

1/7 "The Mystery of SARS-CoV-2 & the Origins of COVID-19" with @Ayjchan:

Listen here: mindandmatter.substack.com/p/podcast-45-a…

2/7

🧵Mind & Matter content series on @Leafly.

A written content series with a new article each month exploring the relationship between humanity and psychoactive drugs.

In this thread, I will collect links to each article in the series.

All articles: leafly.com/news/tags/mind…

1/ "Death and psychedelics: How science is reviving this ancient connection"

Explores the relationship between #psychedelics & death. It integrates the perspective of thinkers ranging from Timothy Leary to Aldous Huxley to @BrianMuraresku.

Read here: leafly.com/news/science-t…

2/

Just learned that fluvoxamine, a common SSRI used to treat depression and other psychiatric conditions, increases the half-life of caffeine in the bloodstream.

Like, to an absurd degree:

1/ Fluvoxamine does this by inhibiting a cytochrome P450 enzyme that metabolizes caffeine. Caffeine levels remain elevated for way longer than normal.

This would be bad for sleep.

2/

🧵"Psychoplastogens" = drugs that rapidly induce physical changes in the brain (neuroplasticity).

Examples: ketamine, psilocybin, LSD, DMT, MDMA.

Neuroscientists can literally watch new connections sprout overnight, as in the example below.

Movie:

1/ There are other plasticity-promoting psychoactive drugs, such as SSRIs, that are not psychoplastogens because they induce plasticity on a slower time scale (weeks).

Psychoplastogens can stimulate plasticity when exposed to neurons for <1 hour.

pubs.acs.org/doi/abs/10.102…

2/

#ScienceBreakdown:

"The Phytochemical Diversity of Commercial #Cannabis in the United States."

This is a preprint for a study I recently completed with collaborators at @CUSystem: @bkeegan, @cannagenomics.

Descriptive summary of the study below.

biorxiv.org/content/10.110…

1/ Some questions we asked:

How diverse is #cannabis in the US in terms of cannabinoid + terpene content?

Are similar or distinct chemical phenotypes (chemotypes) seen across US states?

What are the most common chemotypes we reliably see and about how many are there?

...

2/

#ScienceBreakdown: A group of scientists (@DEOlsonLab) created an ibogaine analog lacking nasty properties of ibogaine but retaining desirable ones. It is also claimed to be non-hallucinogenic.

Background and dissection of study below.

Full study: sci-hub.st/https://www.na…

1/ Background:

Ibogaine is an alkaloid found in iboga, a shrub from West Africa. It's a dissociative psychedelic and can induce intense hallucinations that last for many hours.

Prelim evidence suggests it may help treat addiction, but it can also have serious side-effects.

2/

#ScienceBreakdown: Is DMT produced by the pineal gland in the mammalian brain?

I often see this claim on the internet and am surprised how often I'm asked about it. Below, a breakdown of a 2019 study in (mostly) rats looking at this.

1/n

#psychedelics

nature.com/articles/s4159… For those that don't know, DMT is arguably the most powerful hallucinogen. It's typically smoked/vaporized. Subjective effects are intense but short-acting (minutes). The peak minutes produce a completely transformed experience, utterly alien compared to normal consciousness.

2/

#ScienceBreakdown: "Administration of THC Post-Staphylococcal Enterotoxin B Exposure Protects Mice From Acute Respiratory Distress Syndrome."

Full study here: frontiersin.org/articles/10.33…

Breakdown of the study in this thread.

#cannabis

1/ Acute Respiratory Distress Syndrome (ARDS) = deadly condition where lungs get super inflamed b/c immune system responds too strongly. This leads to lots of collateral damage to throughout the body.

Mortality rate in humans = 38.5%. No current drugs exist that help very much.

2/

Getting questions about recent @Forbes article. Article makes good points + gives good advice, but also makes erroneous claims based on misreading recent #cannabis research. Basic claims of article + breakdown of the new study in this thread. 1/

forbes.com/sites/chrisrob… Many #cannabis consumers buy weed based on THC level, trying to get the most THC for their $. High THC weed sells faster. Article says that buying weed based just on THC is a bad idea. There's more to quality than just THC %. I agree with this, but the article goes further... 2/

1/n, Several people asked me about this headline, on a recent preprint claiming that #cannabis extracts high in #CBD have, "the potential of reducing [#coronavirus] infection by 70 to 80 percent.” Quite a claim. Let's briefly look at the study... 2/n, Remember, this a preprint, so hasn't been peer-reviewed and people are rushing to get #COVIDー19 related studies out ASAP. Let's briefly look at what they did and some results. Are the experiments/results compelling, or is this an absurd rush job (place your bets now!) ...