Can a Guacamole Overdose Kill You?-Part 2
The Skinny on Sitosterolemia- How This Rare Genetic Disease Can Accelerate atherosclerosis.
This picture of an avocado, whose texture is due to its high content of plant sterols, is reproduced by subscription to Shutterstock.
Here is the second installment on sitosterolemia. Please refer to the previous post for the introduction to sitosterol and why we are covering the topic. https://pauldthompsonmd.substack.com/p/can-a-guacamole-overdose-kill-you
When should clinicians entertain the possibility of sitosterolemia.
Clinicians should consider the possibility of sitosterolemia and consider measuring blood sitosterol blood levels or performing a genetic analysis:
o In young patients with xanthomas and normal or only moderately elevated cholesterol levels
o When there is an extremely good response to a low cholesterol diet
o When there is an extremely good LDL-C reduction in response to ezetimibe and/or bile sequestrant resins
o When there is a poor LDL-C response to statins.(1)
· Clinicians should also consider the possibility of sitosterolemia in patients with unexplained hemolytic anemia or macrothrombocytopenia (1) because sitosterol can affect membrane function of red cells and platelets.
· The good LDL response to a low-cholesterol diet is because defects in ABCG5 or 8 enhance cholesterol absorption, by reducing intestinal cholesterol excretion. So reducing the dietary cholesterol reduces the chance for absorption. Interestingly, most cholesterol in the gut is produced by the liver, but when there are ABCG5 or 8 defects, less hepatic cholesterol is excreted into the bile, again increasing the importance of the dietary cholesterol.
· The good LDL response to ezetimibe is because ezetimibe blocks the NPC1 L-1 receptor which mediates intestine sterol absorption, so ezetimibe reduces the augmented sitosterol and cholesterol absorption caused by the genetic defect.
· The LDL cholesterol reduction with bile sequestrants may be 50% vs the 17% usually experienced with these drugs.(1) I am not sure why this happens.
· The poor LDL response to statins is because statins reduce hepatic cholesterol production, but hepatic cholesterol production is already reduced in sitosterolemia because of the over absorption of dietary/biliary cholesterol.
· The diagnosis of sitosterolemia requires direct measurement of blood sitosterol levels or genetic testing. This should be considered for any of the signs noted above or for unexplained hemolytic anemia or platelet disorders.
· This test can be ordered from Quest or by sending samples to Boston Heart Lab. Specifics for getting the measurement are available on the Boston Heart Lab website. (I have no financial connections with this company.)
We are going to take another break here and finish up this topic next week with the most important question of all: Can heterozygosity for defective ABCG5 or 8 genes causes coronary artery disease, such as in the case of Joe Moore, the University of Alabama quarterback discussed in Part 1 of this topic? Sorry to delay the answer but I really want to keep all of these reasonably short so that you have time to read them.
Dr. Ernie Schaefer, Founder and Medical Director of Boston Heart Labs, advised me in preparing this post, but is not responsible for the final product..
1. Yoo, E-G. Sitosterolemia: a review and update of pathophysiology, clinical spectrum, diagnosis, and management. Ann Pediatr Endocrinol Metab. 2016 Mar;21(1):7-14. PMID: 27104173
#atherosclerosis #coronaryartery #cholesterol #phytosteral #sitosterol #ezetimbie #bile