I often receive questions about phytosterols & their probable connection to Atherosclerosis.
#plant-based adherents often promote these plant sterols for their lowering effect.
If these sterols are PER SE atherogenic, that seems quite DANGEROUS.
A look at the evidence 1/12
#plant-based adherents often promote these plant sterols for their lowering effect.
If these sterols are PER SE atherogenic, that seems quite DANGEROUS.
A look at the evidence 1/12
Some context: Phytosterols are similar to cholesterol, serve as structural components of the membranes of plants, just as cholesterol does for our cells.
Our body tries to prevent absorption through transporter ABCG5/8 also interpreted as a “defense mechanism” against them.2/12
Our body tries to prevent absorption through transporter ABCG5/8 also interpreted as a “defense mechanism” against them.2/12
In 1976, we first detected these sterols in atherosclerotic plaque buildup.
Even more worrisome is that they seem to already build up in infants pre-birth crossing the placenta and being worsened by vegetable oil-based infant formula after birth. 3/12
pubmed.ncbi.nlm.nih.gov.
Even more worrisome is that they seem to already build up in infants pre-birth crossing the placenta and being worsened by vegetable oil-based infant formula after birth. 3/12
pubmed.ncbi.nlm.nih.gov.
Now let's take a first principles look at the evidence and go from a zoomed-in perspective(in vitro) up to human outcomes and see what we can glean from this regarding the effects of phytosterols on ASCVD.
4/12
4/12
In vitro: there is evidence for cytotoxic effects on endothelial vein cells and necrotic death in macrophages.
This could hypothetically lead to induced macrophage death --> plaque necrosis --> plaque rupture and eventually cardiovascular events.
5/12
sciencedirect.com
This could hypothetically lead to induced macrophage death --> plaque necrosis --> plaque rupture and eventually cardiovascular events.
5/12
sciencedirect.com
unlike potentially beneficial apoptosis (controlled cell death), necrosis(uncontrolled) is always detrimental
6/12
6/12
Animal: Comparitive studies comparing phytosterols vs ezetimibe.
both groups lowered cholesterol equally.
the phytosterol group had double the atherosclerotic lesions, impaired vasorelaxation, increased cerebral lesions, increased fibrinogen, & higher blood pressure.
7/12
both groups lowered cholesterol equally.
the phytosterol group had double the atherosclerotic lesions, impaired vasorelaxation, increased cerebral lesions, increased fibrinogen, & higher blood pressure.
7/12
Animal: if you knock out, our phytosterol defence mechanism(ABCG5/8) in mice.
When these mice are fed a normal diet they accumulate these phytosterols in organs & develop complex cardiac lesions. If supplemented they developed hepatosplenomegaly and die prematurely.
8/12
When these mice are fed a normal diet they accumulate these phytosterols in organs & develop complex cardiac lesions. If supplemented they developed hepatosplenomegaly and die prematurely.
8/12
Human: Sitosterolemia is a similar rare genetic mutation in ABCG5/8 in humans and is associated with xanthomas, severe coronary heart disease, aortic stenosis, hematologic disorders, and early cardiovascular death.
9/12
9/12
Human: multiple case, retrospective, & prospective cohort studies found significant associations between higher phytosterol levels & cardiovascular diseases.
As of this moment, there are no prospective, placebo-controlled, randomized trials to investigate this link.
10/12
As of this moment, there are no prospective, placebo-controlled, randomized trials to investigate this link.
10/12
Human Mendelian Randomisation: When looking at a predicted equal increase in non-HDL Cholesterol, the genetics SNPs related to Plant sterols resulted in a 2x increase in CVD risk compared to other non plant sterol related SNPs resulting in 1,5x.
11/12
academic.oup.com
11/12
academic.oup.com
So as a closer I will leave you with this quote from @drlipid, which he made on a #PlantBased podcast known for promoting these plant sterols.
He said it quite well and on this occasion I agree, it might also be a clue towards our evolutionary diet😉 12/12
#carnivorediet #keto
He said it quite well and on this occasion I agree, it might also be a clue towards our evolutionary diet😉 12/12
#carnivorediet #keto
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