This is a frequent topic which I get a lot of questions about. Why don’t my pre-workout supplements keep their full efficiency after a couple of uses.

The need to alternate or switch supplements

You’ve been in this situation: you start a new supplement, you get an amazing effect from it, then 2 weeks later, nothing. No more of that feeling you were looking for?! What happened?

The answer is pretty simple: homeostatic equilibrium

In simple terms, your body and brain have balanced themselves. This is one of the reasons that taking the same nootropic, stimulants or any supplements that create an immediate effect will eventually stop working. The problem is not with the supplement, but the mechanism by which our body regulates itself and deactivates or removes receptors to keep the body stable.

The best example is caffeine. If you are not used to drinking coffee, your first cup will give you a nice stimulation, better focus, better mood, and higher energy. Caffeine increases dopamine and adrenaline levels in the brain, which is why you have that increased state of mind and feeling of presence. A lot of pre-workout supplements count on it to give the users the feeling of it “working’’ in the workout.

It creates a difference in the average level of those neurotransmitters. While you can love this feeling, your body and brain don’t like to be off balance. So, to counteract this, they will gradually deactivate or even remove dopamine receptors so that it doesn’t get that imbalance any longer. This is also one of the reasons why you get a lower mood when coming off a stimulant.

How can we keep the effects in the long term?

  • Include some off days:

What you need to understand first is that you can’t always be 120% of what you can be. It’s overkill. You need to get off your stimulant 2-3 times a week, at least. Off days are relatively good for this, as you need to mobilize less energy and less focus, so why not let your body recover by itself.

  • Use more than one product to get stimulated:

Another strategy is to keep more than one product on hand. At least 2 or 3 would be ideal.

Let’s say that on Monday, you have a heavy workout session to do. Focus on supplements that will stimulate the nervous system, motivation, and willingness, mainly, dopamine precursors and releasers.

Here’s a suggested stack:

  • Dl-phenyalanine
  • L-tyrosine or N-acetyl-tyrosine (just a more available source of tyrosine, crosses the blood-brain barrier, so less dose is needed and acts directly in the brain)
  • Theacrine or methylliberine (same effect but shorter action, good if you are working out later in the day)
  • Caffeine + L-theanine (increases the focus effect of caffeine while decreasing the jittery feeling)

If on Tuesday you have a more bodybuilding focused session, more hypertrophy work and time under tension, using less weight – why boost your nervous system to the sky? You don’t necessarily need that boost to complete the task. Instead, focus on supplements that will increase the mind-muscle connexion, quality of contraction and blood flow in the muscles.

Here’s a suggested stack:

  • Beet roots
  • L-citrulline
  • Beta-alanine
  • Glycerol

If you need to increase focus, I would instead act on a subtler stimulation and less dopaminergic effect. Play on acetylcholine to increase the quality of muscle contraction. Increasing acetylcholine will also release some dopamine and noradrenaline but to a lesser extent.

Suggested stack:

  • Phosphatidylserine (helps with brain plasticity and fluidity and also helps to keep cortisol at healthy levels)
  • Choline bitartrate or alpha GPC (acetylcholine precursors)
  • Rhodiola Rosea will help with the reuptake of dopamine and keep more of what you naturally produce

On Wednesday, you could train a more strongman or athletic type of workout, or more cardiovascular demanding session, which will require a lot of energy produced and more endurance. Focus on supplements that support the mitochondria, cardiovascular and energy released.

  • CoQ10
  • PQQ (pyrroloquinoline quinone)
  • Cordyceps (studies show an ATP increase of 18%, will also create some dopaminergic effect by increasing levels of tyrosine hydroxylase, which is an enzyme that converts tyrosine in L-DOPA, direct precursors to dopamine. Another way to increase mood and motivation by a different pathway.)

If you wish to increase focus and attention span, focus on a different pathway than the preceding days.

  • Theobromine, a natural product of cocoa, is part of the methylxanthine family which share similar stimulation effects to caffeine, but act on a different pathway which will not add to the tolerance effect you can develop by consuming the same product every day.

Now there can be a withdrawal to always trying to boost neurological functions. The main concern is to keep sensitivity to the receptors. For example, always tapping into the adrenaline receptors can only lead to desensitization, and you don’t want this. So, to counteract this accumulation effect, you should find strategies to help regain sensitivity to receptors.

Magnesium is one of the best ways to help adrenergic receptors getting off adrenaline. This will turn your CNS off to a lower degree and helps you relax.

Glycine is also a great way to lower cortisol production, which becomes essential especially if you’ve been working out some heavy sessions, which can make your CNS overrun and creates fatigue and dopamine depletion over time.

Another way to help lower CNS and brain activity is to increase GABA production. To assist this process, I like to use Taurine as it promotes GABA production and also helps P5P (bioavailable vitamin B6) productivity and communication in the conversion of neurotransmitters.

Another supplement I find really useful when punching neurotransmitters through hard workouts and high stimulation is Bacopa. It has a unique ability to increase and balance more than one neurotransmitter, mainly serotonin, dopamine, noradrenaline, and acetylcholine. So, it creates a sense of control and well being, leading to less cortisol being produced. This is what we call ‘’mood equilibrium’’.

Phosphatidylserine (PS) is probably the icing on the cake when we talk about equilibrium. PS has the ability to increase brain plasticity and fluidity but also helps to regulate cortisol and ACTH levels (Adrenocorticotropic hormone – which controls cortisol levels too).

What we can see in most studies is that PS is able to lower and balance cortisol levels with only 400mg. But not only can it balance cortisol levels, it also increases focus and attention span by improving the communication and signaling between neurons.

How to stack this out?

I would use PS and Bacopa on days next to your heaviest or most CNS driven workouts. It would be then used as a ‘’recalibration’’ day to help balance neurotransmitters and get ready to knock another heavy day later in the week. I would also use taurine 2-3 x on this day, totaling 3-5gr at the end of the day.

As for magnesium and glycine, I suggest you take them two times a day on your heaviest sessions. Ideally, immediately post workout to help in freeing the adrenergic receptors, which has higher chances to stay activated by adrenaline on heavy sessions.

You should also take another dose in the evening or before bed to continue the release of the receptors and to keep a longer time with low cortisol production. This will also really help in the recovery process.

Let’s give you a concrete example:

Monday heavy session

Post workout: 3gr glycine + 250mg magnesium glycinate (the bounded amino acids glycine will lower cortisol)

Before bed: 3gr glycine + 250mg magnesium taurate (the bounded amino acids taurine will increase GABA, more suited for pre-bed use)

Tuesday bodybuilding session (or less CNS driven)

Morning: 2gr taurine + 150mg bacopa

15-30 min pre-workout: 2gr taurine + 400mg phosphatidylserine

Evening: 2gr taurine + 150mg bacopa

Applying this for a couple of weeks will make a great difference in your recovery process but also keep the efficiency of your pre-workout supplements and help you get more productive workout sessions.

What you need to know

Our body has some amazing mechanisms to keep its balance and homeostasis. Supplements will always keep their effect but our body will protect itself by deactivating or removing receptors so they won’t continuously destabilize our system.


Stéphane Aubé

Written by Stéphane Aubé

Stéphane Aubé has worked in the fitness industry for more than 12 years. He works as a trainer and advisor for Hungry For Victory, a company he founded which specializes in nutrition and physical development for athletes of all disciplines. He has wo…