A seed oil toxic metabolite accumulates and damages human hearts

4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification (2023)

In a nutshell

Ignore the fiendishly complicated title of this paper…
…we now know how a seed oil metabolite can cause human heart disease
Avoid the accumulation of seed oil metabolites for good health

We are only just beginning to understand how certain “chronic diseases” are actually forms of malnutrition caused by industrially processed ingredients in our food

Context

One of the most harmful industrially processed food ingredients is seed oils, a subject which I’ve addressed in detail and updated more recently.

Seed oils deliver unnaturally high and toxic levels of linoleic acid (LA) when we use them for cooking and in things like salad dressings, mayonnaise, etc. LA is chemically very unstable and when it becomes incorporated in our cells it breaks down into reactive and harmful metabolites. One of those metabolites is a compound called 4-hydroxynonenal (4-HNE) [1].

4-HNE is the subject of this paper [2] review.

Objective and results of the investigation

The authors set out to investigate the ways in which 4-HNE damages the human heart, and how its effect might be lessened or reversed.

The authors identified a pathway in mitochondria in which accumulation of 4-HNE did result in heart failure in rats tested. The pathway is presented as a perpetuating cycle:

4-HNE accumulates in the cell
Accumulated 4-HNE directly affects an enzyme (Dicer) that is responsible for creating certain genetic material (microRNA)
Lack of microRNA leads to heart failure
The failing heart produces less of the enzyme responsible for 4-HNE clearance

This process as presented by the authors begs the question - where does it start? I suspect it’s a case of the natural level of 4-HNE production being exceeded because mitochondria contain unnaturally high levels of unstable LA (from seed oil). The unnaturally high levels of 4-HNE then create damage through the pathway described.

The authors also showed that the harmful effects of accumulated 4-HNE can be reversed. They achieved this by stimulating production of the enzyme that breaks down 4-HNE. They boosted the production of the useful enzyme with a pharmaceutical drug.

Why is the paper interesting?

When I wrote about how unnaturally high levels of LA in seed oils cause harm, I stated:

“When we consume too much LA, our mitochondria accumulate too much of it. This causes a change in membrane structure and the production of harmful metabolites. Both lead to mitochondria becoming less effective.”

This paper shows the pathway through which one of the harmful metabolites (4-HNE) causes mitochondrial damage.

I also find it interesting that the authors recommend pharmaceutical intervention to reverse the harmful effects of a seed oil metabolite. They do not advocate simply not consuming seed oils in the first place.

How does the paper help me to understand health and longevity?

The more I understand something, the more confident I become in the steps I take for my health. This paper, provides significant evidence for the way in which unnaturally high levels of LA from seed oils in the human body cause harm. For my part, they have no place in my diet.

Study outline

A series of measurements were made on failing hearts from rats and humans. No human clinical studies were involved.

References

Mercola J, D'Adamo CR. Linoleic Acid: A Narrative Review of the Effects of Increased Intake in the Standard American Diet and Associations with Chronic Disease. Nutrients. 2023 Jul 13;15(14):3129. doi: 10.3390/nu15143129. PMID: 37513547; PMCID: PMC10386285.
Kiyuna LA, Candido DS, Bechara LRG, Jesus ICG, Ramalho LS, Krum B, Albuquerque RP, Campos JC, Bozi LHM, Zambelli VO, Alves AN, Campolo N, Mastrogiovanni M, Bartesaghi S, Leyva A, Durán R, Radi R, Arantes GM, Cunha-Neto E, Mori MA, Chen CH, Yang W, Mochly-Rosen D, MacRae IJ, Ferreira LRP, Ferreira JCB. 4-Hydroxynonenal impairs miRNA maturation in heart failure via Dicer post-translational modification. Eur Heart J. 2023 Nov 21;44(44):4696-4712. doi: 10.1093/eurheartj/ehad662. PMID: 37944136.