so I think if you forget actual drugs on the market that we know of and how they work, the question is purposely not asking you that specifically...If you flip it in your head to think what the problem is that leads to inc TG its because of VLDL therefore they said administering a DRUG with which of the following EFFECTS is MOST appropriate--->DECREASING VLDL b/c that's the culprit

Although drugs we know of have the other characteristics, for this guy, we would be looking for the effect of VLDL everything else is a side thing that doesn't directly address his condition

Fibrates decrease triglycerides by reducing the production of VLDL.

The answer is due to an exception outlined here where niacin is used in pts w/o diabetes who have refractory hypertriglyceridemia at high risk or has a hx of pancreatitis.

I agree that fibrates are first line (and so does that article) but NBME was honing in on a specific exception that niacin can also be used since VLDL and TGs are high in hypertriglyceridemia.

The "clue" they had was "recurrent pancreatitis" which is supposedly a lead towards niacin.

I also put increase HDL....

Fibrates, used for hypertriglyceridemia, act by upregulating LPL, which on its way transforms VLDL ( and CHYLOMICRONS) in free fat acid that will be stored in adipose tissue> therefore DECREASING VLDL LEVELS .

Other than chylomicrons, VLDL have the highest triglyceride content of any of the lipoproteins. Since decreasing chylomicrons isn't an option, decreasing VLDL is your only choice to keep it out of circulation.

After I did this NBME, I got QID 166 wrong (I put niacin); and now I'm not sure which is the right way to think about it. In 166, the pt has hyperTG and answer is to treat him with fibrates to prevent recurrences - idk if anyone else had this confusion.

First Aid Page 94

Type 4 -hypertriglyceridemia is caused by Hepatic overproduction of VLDL. If we just consider the primary issue, then it is easy to see why decreasing VLDL would be the answer.

(full disclosures, I also was think about the types of medication that should be used)

Guys, there are two ways to go about this question:

You recognize this guy has familial hypertriglyceridemia.

1. You recognize that chylomicrons and VLDL are the only two triglyceride molecules in this entire list. This narrows it down to 1 answer, decreasing VLDL, because the other answer choice was to increase chylomicrons. Boom, this is one way of answering it.

2. You recognize that we give fibrates for hypertriglyceridemia. They have 1 MOA, which is to active peroxisome proliferator activator alpha, and that increases HDL levels, decreases VLDL levels, and upregulates Lipoprotein lipase. This also narrows it down to two options, increase in HDL and decrease in VLDL levels. Whats the function of HDL? it leads to CETP upregulation and decreases cholesterol levels. It isn't useful in the reduction of triglycerides. Boom, your answer is still decreasing VLDL.

from uworld: fibrates activate PPAR-alpha to increase LPL and decrease VLDL production

familial HyperTG is is due to overproduction of VLDL. It's familial dyslipidemia type 4. Annoying to keep all of those straight but check out FA p.94 (2018)