Posted by: leigh | August 5, 2012

Fat-soluble molecule exposures and changes in body composition: an exercise

I received a very polite and well-thought out question that I would be remiss in not answering. Sorry it’s taken a while, micycle, life has taken several sharp left turns on me this week.

As a principle, I don’t give medical advice or anything that might sound like medical advice. I actually skirt the whole giving any kind of advice on the internet thing when it comes to the things people do with their bodies, in favor of informing them what the effects may be. So in response to such a question, I am going to just put some discussion out there about what happens when one is exposed to a fat-soluble molecule and then loses or gains a bunch of weight.

Now, say I’ve got a friend Joe who has some substantial fat stores and a friend Tim who has lesser fat stores. Joe and Tim happen to be hanging out together in the wrong place at the wrong time, and they are both exposed to the same weight-adjusted dose of a fat-soluble drug, let’s call it X.

What is the first thing that X does? It gets into the bloodstream and circulates around the body. As soon as it encounters some fatty tissue, it will preferentially move to the fat and hang out there. The rest is sent around the body, causes whatever effect it may cause on various body systems, is broken down by the liver, and eventually gets sent out of the body.

Who has a greater initial exposure effect- Joe or Tim? Joe has more fat to sequester the X molecules, so the rest of his body is exposed to a lower effective dose immediately. Tim has less fat and more of the X affects his organ systems acutely.

What about in the longer run? Who is worse off? The stored X equilibrates out of the fat over time to provide Joe with a longer duration, lower-level exposure. If X has toxic effects, Joe will likely need continued treatment to counter the effects of X over several weeks. Tim, on the other hand, is much more likely to recover fairly quickly with prompt treatment.

What if Joe loses weight? What will happen? Will he get rid of the X more quickly? If Joe substantially decreases his body fat (not just a pound or two), his fat cells will become smaller. The X will become more concentrated, and the concentration gradient between the blood and fat will become greater. This will favor more X equilibrating from the fat to the bloodstream so that it can be metabolized and cleared. It will also cause an acute toxic syndrome, if X has toxic effects, as the drug once again affects his organ systems. Eventually the blood concentration of drug will drop below the threshold that causes systemic effects/can be detected but this is not going to be immediate. It’s worth noting that we’re talking a pretty substantial weight loss, and a couple lbs here or there for your average 175-lb adult male would not have such dramatic effects.

What if Joe gains weight? Will he extend the amount of time required to clear the drug? A substantial weight gain would decrease the concentration of X in the fat cell as the fat volume increases inside the cell, but there would still be more X in the fat than in the blood. So the concentration gradient would still favor release of X into the bloodstream. Whether or not the concentration of X in the blood would be below the lowest adverse affect exposure level- or detectable- depends on the amount of X that was stored in the fat to begin with.

How about if Joe just eats a lot of fatty foods- will that slow the release of X into the bloodstream? The factor of interest here is the difference in concentration between X stored in the fat cells and X circulating in the bloodstream. Adding fatty acids to the bloodstream does not change this factor. So, no, eating a lot of fatty foods will not help except in the case of preventing weight loss.

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  1. I think you just got conned into doing some kid’s homework for him.

  2. nah, he wanted advice on passing a drug test by losing weight and then eating a lot of fatty foods. i don’t do advice on that so i wrote this instead, he can arrive at his own conclusions.

  3. That was a fun post :)

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