I had a request to write a post on supplement timing, that is, how time of day or other timing such as with meals, or whether in the fed or fasted state, matters. I practice timing of supplements myself, although the hard scientific evidence for these practices is sparse. Nevertheless, I think reasons and logic make a fairly compelling case for doing so.
Categories of Timing
Timing of supplements can be broken down into various types. Here’s how I would classify them.
1. Time of day, such as in the morning or evening.
2. Fed or fasted. Some supplements may be absorbed better on an empty stomach, others with a meal. Perhaps more importantly, some supplements could abolish the effects of intermittent fasting.
3. Anabolic or catabolic phase. Humans have a strong diurnal rhythm of anabolism and catabolism, and derangement of this rhythm, that is a weakening of the amplitude of these processes, is a prominent cause of aging. Maintaining peak health and slowing aging requires that attention be paid to the rhythm of anabolism and catabolism, so that amplitude does not diminish and these processes continue to operate as they would in young, healthy people. Therefore, if a supplement can either augment or diminish these, one must time the supplements properly to ensure good regulation of our diurnal rhythm that rids us of junk and builds new, better functioning physiological machinery.
Let’s look at each of these.
Time of Day
The late Seth Roberts used to discuss taking vitamin D in the morning. He and a number of his readers reported much better results from doing so, particularly on sleep. The logic of this is that vitamin D is normally produced in the skin by the action of sunlight, and therefore we may be adapted to receiving vitamin D during the daytime. Whether that time is morning or the afternoon may obviously vary, but it seems clear enough that it would not be at night. Vitamin D taken during the day may reinforce our circadian rhythms; taken at night, it may disrupt them, and thus disrupt sleep and any number of other physiological processes.
To my knowledge, there are no scientific studies on whether this effect is real, but it does make sense, and I don’t think anecdotal accounts should be disregarded. Since it’s no great difficulty to take vitamin D at one time of the day or another, I follow this guideline by taking it in the morning.
Another supplement that can be usefully taken according to time of day is magnesium, which in this case should be taken at night. Magnesium promotes relaxation and thus may promote restful sleep. Some readers of mine have reported that magnesium completely cured their insomnia. I follow this guideline also and take 200 mg magnesium citrate right before bed.
Fed or Fasted
This category has some overlap with anabolism and catabolism, since if you have fasted long enough you will be in a state of catabolism, if fed, you are in anabolism.
N-acetylcysteine (NAC) is a supplement that should be taken with a meal. The rationale for NAC is the replenishment of the body’s most abundant and important internal antioxidant, glutathione. NAC supplies cysteine, which is rate-limiting for glutathione synthesis, but glutathione’s other two building blocks are glycine and glutamate, the former an amino acid, the latter derived from one. Older people do not appear to have diminished levels of glutamate, but they do have lower levels of glycine. These components are equally necessary, and if NAC is taken in the fasted state, glycine may be lacking, and therefore no glutathione is synthesized. So if you supplement with NAC, eat some form of protein with it.
Curcumin by itself is readily metabolized by the liver, and for this reason many supplement manufacturers have added piperine, a derivative of black pepper, to their curcumin. Piperine inhibits the metabolism of curcumin. But curcumin is also difficult to absorb from the gut, and a high-fat meal increases absorption greatly. So I take curcumin with a high-fat meal – and since just about all of my meals are high fat, no problem.
I take zinc with meals for a simple reason: it can make me feel slightly nauseous on an empty stomach. Others have reported this to me as well. If it doesn’t do that to you, then no big deal, otherwise, take it with food. I have no problem with it when I do that.
Anabolism and Catabolism
This is perhaps the most important category. If you are fasting for health – as opposed to doing it to lose weight – you do so because fasting increases autophagy, so you don’t want to take a supplement that might hinder that. If in anabolism, that is during the fed state or around workouts, the same holds, you don’t want to diminish it, and you do want to enhance it.
In the fasted state, I take resveratrol, which I avoid around workouts. Resveratrol enhances autophagy and diminishes IGF-1 and mTOR signaling, so it should increase the benefits of fasting. Whether the effects of resveratrol are strong enough to decrease anabolism from a workout is something I doubt, but I think no one really knows, and since it isn’t difficult to arrange my timing, I don’t take it within a few hours, before or after, workouts.
Lithium extends life by promoting autophagy. However, the mechanism by which it does so is independent of mTOR, meaning that it is not connected to fasting or workouts. Therefore I’m indifferent as to when I take lithium.
As we’ve noted many times here, both fasting and calorie restriction promote longevity. But antioxidants may not only abolish the health effects of exercise, but also abolish the health effects of calorie restriction and intermittent fasting. In this regard, vitamin C is the most important antioxidant, so do not take this when fasting or exercising. Vitamin C diminishes or abolishes the radical oxygen species that are important signaling molecules in exercise and fasting, and which signal the cells to upgrade their stress defense mechanisms and to grow muscle. On days that I take vitamin C, I do so long after workouts and when I’m in the fed state.
Whey is the anabolic protein par excellence. When taken before or after workouts, it enhances anabolism by providing a high level of essential amino acids and branched-chain amino acids (BCAAs). At this point, it perhaps goes without saying that it should not be taken when fasting, as it will totally abolish autophagy. Take it around workouts and in the fed state. Perhaps less obvious, if you take either BCAAs or leucine as a supplement, which I do myself sometimes, this will also abolish autophagy. Take these during the fed state if you fast for health.
Creatine I don’t think has an effect one way or another on autophagy or fasting, but as a matter of convenience I add it to my whey shakes and therefore take it during the fed state.
You should be cognizant of whether a particular supplement interferes with intermittent fasting or anabolism or exercise, and take them at the appropriate times. You want to see results from all the hard work you do, whether in the gym or in kitchen avoidance, and some supplements either enhance or interfere with that work. Likewise, you want to sleep well, and also get the most benefit from your supplements.
If any readers feel that I’ve omitted something, or have questions, by all means let me know.