The more, the better: N-Acetylcysteine and pharmacokinetics

As you probably know, N-acetylcysteine (NAC) is a highly used antioxidant. NAC is not a bogus medicine. Its reducing capacity makes it a valuable antidote of acetaminophen poisoning. Apart from its utility as mucolytic, NAC is a common ingredient of many “anti-aging pills”. The idea behind NAC as anti-aging agent is that it would protect the cells from oxidative stress. NAC is pretty safe, so it can be administered for long periods at significant doses without visible side effects. It would be nice, however, to know how much and how often it should be administered. This leads us to NAC pharmacokinetics. It is not our today’s objective to write a treatise on pharmacokinetics, so we will go through a couple of concepts to illustrate where is the point. A simple definition will suffice: Pharmacokinetics is what the body does to the drug. Being so, it implies:

• The absorption of the drug.
• The distribution of the drug among all its organs.
• The metabolism of the drug.
• The elimination of the drug and its metabolites.

A simple and informative way to have a gross view of what happens to a drug in humans it to administer it and take blood samples at defined intervals. In the case of NAC, if it is administered orally we will be able to know how much of it enters the blood stream, and how long it stays there.

We are in 2006 at the time I am writing this, and it may seem that any study on NAC that is 15 years old is probably irrelevant. After all, a blog is about hectic news, isn’t it?

In fact, by 1991 there were even reviews published about NAC pharmacokinetics. A fast search in PubMed shows a very interesting piece of information. The terminal half life of NAC if of 6.25 hours. That means that, excluding absorption effects, NAC levels decrease to 50% of its initial concentration in 6.25 hours. Translated to practical words, it implies that a single dose of 200 mg of NAC will be like a 50 mg dose after 12 hours. We don’t know how much NAC is needed to protect from aging. We don’t even know if NAC has any real anti‑aging effect. But it is clear that if we bet for the protective effects of NAC, it is reasonable to expect that high blood levels of NAC will have better chances of showing anti‑aging effects. Given its high safety window, its not probable that maximizing exposure will yield any undesired effects.

Having said all that, the question is: How can we increase exposure with this kind of pharmacokinetics profile? We can increase exposure by dividing the daily dose in as many takes as reasonable. This will ensure an almost constant level of NAC. For this purpose, it is better to take two doses of X mg every 12 hours than taking 2X mg every 24 hours. This assumes that X mg orally is enough for its desired effects.

How can we do this in a practical way?

• We can buy NAC in small doses and take them more often.
• We can divide a big dose in small ones (I don’t like this one, it is cumbersome).
• If NAC is included in a multivitamin complex, we can split the pill of the day and take each half in different moments.

As you can imagine, this analysis applies to any molecule that has a short half life, so it is probably a good idea to divide any anti‑aging complex in fragments, so they can be taken along the day. For the components that have long half lives, it won’t make any difference to take them in more than one dose along the day.

I only know about one of those supplements that are already fragmented. The Kurzweil’s & Grossman’s “Total Care Daily Formula” has a serving size of 6 tablets (yes, I know… quite difficult to swallow). Those six tablets can be taken one by one along the day*. I will be happy to know about other supplements that can have a daily dosage of more than one pill. Do not hesitate to comment on it (or any other issue about this post) if you want to do so.

In fact, I wish there were vitamin/antioxidant supplements formulated like small candies, so I could take one every time I have a craving for something sweet…

Next time we will talk about vitamin C and its pharmacokinetics.

*(I don’t have any relationship with Ray & Terry’s)