Friday, January 15, 2010

Does Tyrosine Supplementation Actually Work for ADHD? (part 1: theory and background)

Can ADHD Symptoms be Cured or Treated via Tyrosine Supplementation?

Due to the extensive nature of this topic, we will be investigating the answer to this question over a number of consecutive blog posts. First, some background on tyrosine, and why it is often a suggested (and even prescribed) on a relatively frequent basis by clinicians for treatment of ADHD and related disorders:

The appeal of a natural ADHD treatm
ent strategy such as supplementation with tyrosine or other amino acids in lieu of drugs:

As a parent, teacher or guardian of an ADHD child (or possibly as ADHD sufferers ourselves), we often have an inherent bias against medications for the attention deficit hyperactivity disorders. This is quite understandable. After all, who really wants to "drug" themselves or their child, especially if a more "natural" benign treatment method is currently available? While many of the claims against ADHD medications are either fabricated (as an example, while many "natural" ADHD treatment websites often love to assert otherwise, Ritalin is not the equivalent to crack cocaine) or over-hyped, there are definitely legitimate concerns and risks surrounding medication treatments for the disorder. Potential complications include:
The list goes on, but we get the idea.


1. There is an imbalance of brain chemicals dopamine and norepinephrine in the ADHD brain:

One of the basic premises of ADHD is that it is caused by a chemical imbalance of certain neurotransmitters in the brain, including dopamine and norepinephrine. While the following description is a gross over-simplification of the process involved, the current theory is that the balance of the brain chemical dopamine inside vs. outside of brain cells is out of whack in certain key "ADHD" brain regions.

(As a side note, here is a link to some of main brain regions believed to be "different" between the ADHD and non-ADHD population, as well as another earlier post on the difference between an ADHD brain and an OCD (obsessive compulsive disorder) brain. Additionally, variations among individuals involving specific "ADHD genes" may play a role in dopamine level differences. Please take each post with a grain of salt, as they are more generalizations and examples than non-negotiable absolutes).

Again, this is a great oversimplification of a complicated process, but the general idea is that most ADHD medications (the stimulants in particular) work by either directly or indirectly increasing the levels of dopamine outside of the neuronal cells in the brain and restoring this imbalance. Please note, however, that this generalized "dopamine deficiency" theory of ADHD is by no means a consensus among the medical profession and is being challenged by some professionals.

2. Direct dietary supplementation with dopamine for ADHD treatment is ineffective:

Our first thought might be to just try to supplement the body with large amounts of dopamine to try to correct this neuro-chemical imbalance. The problem with this strategy is that we have to deal with an entity known as the Blood Brain Barrier.

In a nutshell, the Blood Brain Barrier is a barrier meant to prevent potentially harmful agents in the blood from making their way into the brain. In other words, it is a crucial protective measure which is vital to the survival of our bodies and respective nervous systems from the rapid influx of potentially harmful agents. The problem is that this barrier also screens out a number of potentially helpful agents, including many types of therapeutic drugs (this is one of the biggest challenges in the design of psychiatric medications, in addition to acting on their targets, these drugs must be able to actually get into the brain in the first place).

Unfortunately, it has long been known that the chemical dopamine itself does not have a particularly sound affinity for the blood brain barrier (although a number of "tricks" involving manipulation of protein "transporters" in and around the brain, as well as using slightly modified related compounds have been used to increase levels of this important neurochemical). As a result, direct unaided dopamine supplementation for ADHD does not work. Enter the amino acid tyrosine.

3. The amino acid tyrosine is a chemical precursor to both dopamine and norepinephrine.

Unlike dopamine, the amino acid tyrosine can cross the blood brain barrier (under the right conditions). The following diagram highlights the general pathway (including chemical intermediates) from tyrosine (listed as "L-tyrosine" in the diagram) all the way to dopamine, norepinephrine, and even epinephrine (adrenaline):
(Please note, the diagram depicted above is a reproduction of a larger image originally found here. The blogger apologizes for the low quality of the image depicted here; feel free to check out the larger image in the link above if needed.)

The attempt to generate higher levels of dopamine and norepinephrine by supplying the body with the dopamine and norepinephrine precursor tyrosine is an example of what is known in medicine as precursor loading. As we will see later on, precursor loading strategies are often a mixed bag of rewards and risks, with varying degrees of overall effectiveness. This blogger intentionally wishes to remain neutral on the subject at hand here, with the goal in mind of providing unbiased information advocating both for and against tyrosine treatment for ADHD.

You do not need to be a biochemist or know chemical structures or pathways; the above picture is just simply a visual tool to demonstrate that there are a number of steps in the conversion process of tyrosine to dopamine and norepinephrine. Using the above diagram for reference, we will see that there are a number of "hoops" we need to jump through in order to make tyrosine supplementation worthwhile as a possible ADHD treatment. We will break this down into smaller steps in the next collection of posts and summarize the overall potential (as well as review what the current literature has to say on this process) at the very end.

I have broken down some of the major steps of this process, which need to be considered to maximize the effectiveness of this tyrosine treatment for ADHD. Each of these steps will be addressed in the next few posts:

  1. The supplement must be able to cross the blood brain barrier. This process involves special "transporters", and can be influenced by outside factors, including other dietary amino acids. This will be discussed in the next post.

  2. In order to proceed on to dopamine, tyrosine must first be converted into an intermediate called L-dopa (please note that L-dopa can cross the blood brain barrier as well, and is sometimes used as a prescribed supplement for ADHD treatment in its own right. This will be discussed later on, including advantages or disadvantages of supplementing with L-dopa vs. supplementing with tyrosine).

  3. In order to convert to L-dopa, tyrosine requires the enzyme Tyrosine Hydroxylase, as well as cofactors ("helpers" to the enzyme), which will be discussed in detail in a later section.

  4. In order to convert from L-dopa to dopamine, a class of enzymes known as decarboxylases is needed. This too, requires cofactors (which in this case are specific vitamin and mineral derivatives) to operate properly. It is important to note that deficiencies in these nutrients can severely inhibit this step of the process (and, in the blogger's opinion, can be a seriously overlooked reason for the relative ineffectiveness of tyrosine supplementation in a number of cases, and that simply maintaining adequate levels of these nutrients could greatly aid the process in this crucial step). Again, these challenges will be discussed at a later time.

  5. Norepinephrine imbalances are also seen in many ADHD cases, so the dopamine to norepineprhine conversion process is also important. This, too, requires specific enzymes and cofactors.

  6. It is also critical that we don't overlook side reactions in the process. As we might expect, tyrosine can convert to a number of other things in the body besides dopamine, and the enzymes and systems involved in these pathways often "compete" with one another, each with its own accompanying side effects. These competing processes can cause potential problems, including the depletion of several crucial vitamins and minerals (the B vitamins in particular) and may also cause a buildup of potentially harmful biochemical products (such as homocysteine). Perhaps not surprisingly, some of these key vitamins and minerals used up by the above metabolic processes are often found to be deficient in the general ADHD population.

    We have investigated some of these B vitamin and homocysteine effects with respect to ADHD in an earlier post. The point here is this: if we flood our system with tyrosine, we must realize that we are feeding the first step of a whole slew of biochemical products in addition to our desired end products of dopamine and norepinephrine. We must account for these effects and do everything possible nutritionally to minimize the potential harm of chemical imbalances caused by these processes.
Of course there are other factors besides these six, but hopefully, we can start to see that supplementation with this amino acid in hopes of treating ADHD (or at least reducing symptoms of the disorder) has numerous complications, as well as potential drawbacks and limitations. However, this blogger feels that if we are to have a go with tyrosine supplementation, all the other pieces of this metabolic puzzle (nutrients, enzyme systems and otherwise) must be firmly in place to maximize the effectiveness of this ADHD treatment strategy. While this is certainly a tall order, it is my aim as a blogger to both highlight these necessary puzzle pieces and give potential ways to optimize their effectiveness in the next few posts.