A Conspiracy to Protect Linoleic Acid?

tl;dr: Yeah, it's nuts. But look at the evidence. Why the blind spot?

I have been noticing for years a peculiar phenomenon: papers that ought to be discussing linoleic acid’s role in disease oddly ignore it.

The latest instance, and what spurred me to write this post was an editorial I came across this morning:

“Alzheimer's May Not Actually Be a Brain Disease, Expert Reveals” (Weaver, 2024b)

The title’s a bit misleading, what he means is that it’s a process that isn’t specific to the brain.

“Rather, we believe that Alzheimer's is principally a disorder of the immune system within the brain…”

“We believe that beta-amyloid is not an abnormally produced protein, but rather is a normally occurring molecule that is part of the brain's immune system. It is supposed to be there.” (Weaver, 2024)

I definitely agree that Alzheimer’s is a process that is not specific to the brain, and have written about it a number of times on X.

Link to post.

Beta-Amyloid is not only produced in the brain, but throughout the body (Miklossy, 2010). Additionally, when I interviewed Ameer Taha, I asked him what he would do if someone gave him $1B to do some research project. His answer was: he would want to show that linoleic acid causes Alzheimer’s.

PUFA and Alzheimer’s

So I was pretty excited to go look through Weaver’s recent research and see what he had found to support this:

“Because of striking similarities between the fat molecules that make up both the membranes of bacteria and the membranes of brain cells, beta-amyloid cannot tell the difference between invading bacteria and host brain cells, and mistakenly attacks the very brain cells it is supposed to be protecting.” (Weaver, 2024b)

In heart disease and atherosclerosis, it’s long been known that the oxidized phospholipids on ApoB particles (oxLDL) are indistinguishable from those of certain types of bacteria, and that germ-line (written into inherited DNA) antibodies detect both those common bacteria and oxLDL:

“Furthermore, the E06 antibody gene is identical… to T15 natural antibodies that provide optimal protection against pneumococcal infection in mice…. Thus, there is molecular mimicry between the PC of OxLDL and the PC of pathogen.” (Tsimikas, 2006)

This is not only seen in heart disease.

“Most importantly, the presence of oxidation-specific epitopes is not only restricted to OxLDL and atherosclerotic lesions, but in fact these epitopes are ubiquitously present in inflamed tissues found in many different diseases, including rheumatoid arthritis, Alzheimer’s disease and haemachromatosis [60] amongst others” (Chou, 2008)

Figure 1 from (Chou, 2008)

And it’s been known for decades that dietary linoleic acid is a determinant of the presence of oxLDL (Steinberg, 1990; Witztum, 1991).

The missing fat

Weaver has a couple of very interesting recent papers. One is a survey of Alzheimer’s risk factors (Weaver, 2023), and the other is a survey of endogenous molecules that stimulate the immune system (Weaver, 2024a). In the risk factor paper Weaver states:

“Given the complexity of diabetes, the possible mechanistic links between diabetes and AD are multi-fold and include Aβ misfolding and oligomerization, tau hyperphosphorylation and aggregation, neuroinflammation, damaging pro-oxidative processes and dysfunctional mitochondria.” (Weaver, 2023)

“Pro-oxidative processes” sounds promising, that will involve Ω-6 PUFA, but he only discusses saturated fat, and cites a couple of crappy papers—no diet details—looking at “high-fat, high-cholesterol” diets. There’s no mention of linoleic acid, or even of PUFAs. Which is odd as there’s a whole raft of papers looking at PUFAs and Alzheimer’s disease, and it’s been shown that oxidized Ω-6 fats cause amyloidosis.

“The present study demonstrates a direct cause-and-effect correlation between oxidative stress and altered amyloid-β production, and provides a molecular mechanism by which naturally occurring product of lipid peroxidation may trigger generation of toxic amyloid-β42 species.” (Hardas, 2013)

The other is a survey of “endogenous antimicrobial-immunomodulatory molecules” (EAIM) (Weaver, 2024a). As oxLDL is one of the definitive EAIMs, now we’re talking! He has a section on lipids, in which he states:

“…accordingly, in principle, lipids are a logical structural framework in which to identify endogenous compounds which may be both immunomodulatory and antimicrobial. Polyunsaturated fatty acids fulfil this requirement.” (Weaver, 2024a)

He doesn’t discuss saturated fats at all.

“Polyunsaturated fatty acids (PUFAs), specifically arachidonic, docosahexaenoic, eicosapentaenoic, α-linolenic, γ-linolenic, and dihomo-γ-linolenic acids function as endogenous anti-viral, anti-bacterial, and anti-fungal agents (Figure 5).[49]” (Weaver, 2024a)

Specifically? Wait a minute…

The missing PUFA

PUFAs mentioned in (Weaver, 2024a).

See what’s missing? The #1 fat in the Western diet is a PUFA, the precursor for the other Ω-6 fats, and it’s missing (???, in red). (He leaves out the intermediate Ω-3 fats, which is OK).

His reference for these fats is [49], (Das, 2018). Here’s what he writes:

“Previously, it was suggested that polyunsaturated fatty acids (PUFAs): linoleic, a-linolenic, c-linolenic (GLA), dihomo-GLA (DGLA), arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acids (DHA) function as endogenous anti-bacterial, anti-fungal, anti-viral, anti-parasitic, and immunomodulating agents.” (Das, 2018)

So for some reason Weaver left LA out. This is odd; as mentioned, LA is the primary PUFA in the diet of industrial man, and his own source mentions it first, as is appropriate.

We know that Weaver is familiar with linoleic acid in the context of neurodegeneration because he published this case report in 2018:

“Topically Applied Linoleic/Linolenic Acid for Chronic Migraine” (Santos, 2018)

“Topical”? There are so many things wrong with this idea, which I won’t go into here, but he at least cites another poor-quality paper to justify it:

“Prophylactic Treatment of Migraine with Gamma-Linolenic and Alpha-Linolenic Acids” (Wagner, 1997)

The missing migraine papers

But this is an uncontrolled trial from 1997. The big problem here is that in 2013 the NIH published a RCT on Ω-6 and Ω-3:

“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.” (Ramsden, 2013)

And five (!) other papers looking at the same project, all prior to 2018:

Pubmed link to these papers.

How on Earth do you miss that when looking for research concerning migraine and PUFA, but find a poor-quality 1997 trial from Germany?

“Once is happenstance. Twice is coincidence. Three times is enemy action.”—Ian Fleming

Weaver isn’t the only scientist who fails to mention linoleic acid when he ought to. I’ve been collecting a whole series of such studies and posting them to X.

Here’s an example: