Michelle Marsh Bra Size

Michelle Marsh Bra Size: 32FF

Michelle Marsh is a stunning English glamour model and singer, featured in such magazines as Maxim, Loaded and Perfect 10.

Michelle Kwan Bra Size

Michelle Kwan Bra Size: 30B

Michelle Kwan is a wonderfully talented American figure skater, known as a two time Olympic medalist and five time world champion in figure skating.

ADHD and Vitamin D Deficiency: Any Evidence?

Is there any link between vitamin D levels and ADHD? A review of the current evidence:

We have spent a lot of time looking at correlations between vitamins, minerals, omega-3 fatty acids and amino acids (and their deficiencies) and ADHD. However, it is important to note that just because low levels of a particular nutrient are seen alongside the disorder, it does not necessarily mean that this deficiency is the cause of ADHD (i.e. correlation does not imply causation). In other words, the nutrient deficiency and ADHD symptoms might both be secondary effects of a larger primary cause, such as an enzyme deficiency or metabolic dysfunction.

In the case of vitamin D, the association with ADHD is a lot more muddled than with some of the other nutrients which have a relatively strong connection with the disorder (iron, zinc, magnesium, and omega-3 fatty acids to name a few). The amount of information in the literature is relatively scarce, as well. A search in the journal database Pubmed (where this blogger gets most of his articles and information) for "ADHD" and "vitamin D" turns up only a small handful of search results, the majority of which focus on other disorders and only mention ADHD peripherally.

However, given the fact that vitamin D is such a "hot" vitamin and has been a popular supplement as of late, we should investigate some of its potential benefits with regard to ADHD and related disorders. Please keep in mind that many of these points below are more theoretical or speculative, because most of the hard, concrete evidence in well-documented clinical controlled studies simply does not exist at the moment. Nevertheless, here are some possible ways in which vitamin D may help in cases of ADHD or related disorders:

• Vitamin D can boost levels of the antioxidant glutathione in the brain. One way that vitamin D does this is by regulating an enzyme called gamma-glutamyl transpeptidase, which plays a role in both the metabolism and recycling of glutathione. We have spoken at length about how antioxidant deficits can worsen ADHD symtpoms, and how fatty acids (namely omega-3's) are frequently administered for ADHD and related disorders. Given the high makeup of these omega-3 fatty acids in the brain, and their susceptibility to oxidation and damage in the central nervous system, protecting them by boosting antioxidant levels (either directly or indirectly) is a good bet.
  
  
• One of the current theories surrounding ADHD is that it is (at least partially) an energy deficiency syndrome, or is the result of impaired metabolic abilities in key regions of the central nervous system. While highly debatable, this theory holds that impaired glucose metabolism in various parts of the brain may be a major contributing factor to the presence or severity of this disorder.
  
  While this blogger is currently neutral on this deficiency theory, it is interesting to note that vitamin D can help regulate glucose tranport into the brain, which would (at least in theory) improve this possible cause of the disorder. It is believed that vitamin D works by targeting multiple enzymes involved in glucose transport and metabolism. Much more study needs to be done to confirm this assertion, but this may be another potential benefit of boosting vitamin D levels in the ADHD patient.
  
  
• Vitamin D may play a role in catecholamine synthesis. Catecholamines include the neurotransmitters dopamine and norepinephrine, both of which are believed to be tightly regulated and highly involved in the treatment of ADHD (deficiencies of both dopamine and norepinephrine in the "gaps" between neuronal cells are often seen in cases of ADHD).
  
  
• Vitamin D boosts the effects of an enzyme called choline acetyltransferase in the mammalian brain. This enzyme is used in the manufacture of another neurotransmitting agent called acetylcholine. Acetylcholine is thought to play a major role in maintaining a state of sustained attention, a critical shortcoming in those with ADHD. In other words, keeping adequate levels of vitamin D could potentially help prop up lower levels of this attention-sustaining neurochemical.
  
  
• Learning and memory deficits, both of which are heavily present in the ADHD population, have been tied to prenatal vitamin D deficiencies in the rat model. This involves a process called synaptic plasticity, which relates to memory formation in an individual. If this finding extends to humans, it could have serious implications on maintaining adequate vitamin D intake in pregnant women.
  
  
• Problems with fine motor control are sometimes seen as a secondary characteristic in a fraction of the ADHD population. These problems may be exacerbated in a vitamin D deficient state.
  
  
• Perhaps the strongest correlation, however, may be between vitamin D and depressive-like symptoms, particularly those associated with seasonal affective disorders (SAD). Please keep in mind, however, that studies on vitamin D levels and depression are highly variable; a number of studies have been done on the topic and found no such linkage between the two. We have previously investigated possible connections between ADHD and SAD in an earlier post.
  
  This may make intuitive sense, since vitamin D production is triggered by sunlight, so in the dark winter months, the levels of this vitamin are often much lower (this may also be a major contributing factor as to why illnesses run so much more rampant during the winter months). In other words, vitamin D supplementation may be particularly useful in individuals with ADHD who also have co-occuring depressive or anxiety-ridden symptoms.

To summarize: Vitamin D does not have as many pronounced direct effects on ADHD as do some of the other vitamins, minerals, fatty acids and amino acids we have previously discussed. Nevertheless, the vitamin does seem to have multiple neurodevelopmental and neuroregulatory properties, and may go well with comorbid disorders such as schizophrenia, speech difficulties, memory problems, and (perhaps most strongly) depressive symptoms. Please keep in mind, however, that it may not be possible to simply "supplement these problems away" with extra vitamin D. This blogger just wants to point out that a deficiency in this vitamin often manifests itself in many ways, some of which closely parallel ADHD or related disorders. Nevertheless, supplementing may not be a bad idea, especially if you live in an area that gets minimal sunlight for part of (or all of) the year. Some rough guidelines for vitamin D intake can be found here.

Do Tyrosine Supplements for ADHD Actually Work? (part 8)

Blogger's note: If you are interested in taking tyrosine as a supplement for ADHD or related disorders, the above diagram is a summary of the key nutrients which interact or play a role in tyrosine metabolism. In this blogger's opinion, we want to avoid deficiencies (or, in some cases, excesses) of any of these nutrients. If you are in a rush and do not want to read this whole posting, this table may be a good starting point. I have listed a number of links at the bottom to other sites as far as recommended daily intakes are concerned for the majority of these nutrients. This list is by no means extensive, but this will hopefully highlight the major impact factors in maximizing the benefits of tyrosine supplementation as an ADHD treatment strategy.

(If the above diagram is not easily visible, most browsers will allow you to left-click the image to get a blow-up version, or you should be able to right-click the image with your mouse and view the image in a new window).

We have spent the past seven postings on the pathway of tyrosine metabolism and the implications of supplementing with this amino acid nutrient (and its derivatives for ADHD). But does it actually work?

For the last seven postings, we have been examining the following metabolic pathway of tyrosine. Included are the major enzymes and key nutrients responsible for this process to occur efficiently:



Here's a brief review of the evidence for (and against) tyrosine supplementation. Much has been covered in the previous 7 blog posts, but some is new. Links to the studies (or summaries of the studies if the full article is not available) are provided in most cases.

Potential advantages of tyrosine supplementation for ADHD:

• Tyrosine is a precursor to common neurotransmitters believed to be involved in ADHD (neurotransmitters are chemicals involved in various signaling or messaging processes in the nervous system) dopamine, norepinephrine and epinephrine (adrenaline). Imbalances (typically shortages) in the regions or "gaps" between neuronal cells of these chemicals often occur in ADHD and related disorders, so the idea with tyrosine is that it can theoretically boost levels of these deficiencies and potentially help correct this imbalance.
  
  
• Tyrosine can readily cross the blood brain barrier. This barrier has been discussed extensively elsewhere, but, in summary, the blood brain barrier is responsible for the passage of nutrients and metabolic products in and out of the brain (and also helps keep harmful agents out of the brain). L-DOPA, a derivative of tyrosine, and the first major product of tyrosine metabolism in most cases, is also able to make it across the blood brain barrier. Most of the major products beyond this point cannot, making tyrosine (or L-DOPA) potential supplementation agents which can be taken orally.



• As a "natural" and common amino acid, tyrosine is something the body already is accustomed to metabolizing through the diet. Note that tyrosine shares several enzymes and transporters with other amino acids and nutrients.



• Numerous anecdotal reports have found tyrosine to be useful for comorbid (co-existing) disorders to ADHD, such as depression. Given the high frequency of comorbid disorders associated with ADHD, tyrosine's versatility may potentially give us some "2-for-1" deals with regards to helping treat multiple symptoms or disorders at once.



• Tyrosine is a good starting point for nutrient-based treatments in metabolic disorders involving the amino acid phenylalanine (such as phenylketonuria). Phenylalaline is converted to tyrosine in a fashion similar to how tyrosine is converted to L-DOPa, via an enzyme-based chemical modification called hydroxylation (in which an "OH" chemical group is added to the molecule).



• Numerous anecdotal reports involving tyrosine supplementation for ADHD symptoms have indicated positive results (at least initially, we will see, however, that many of these benefits are often short-lived).



• Many physicians have (and continue to) prescribe tyrosine for ADHD and related disorders, and, in many anecdotal cases, the individuals taking the tyrosine have seen marked improvement in a matter of days regarding ADHD symptoms (focus, impulse control, decrease in hyperactivity, etc.)



• Tyrosine may be used in conjunction with medications for ADHD and other related disorders. In other words, it may boost their effects (although this may be a double-edged sword, as some of these drugs are potent, so co-supplementation with tyrosine can possibly increase their side-effects and risks by several orders of magnitude in some cases). In this blogger's opinion, this may be the strongest potential use of tyrosine (as opposed to supplementation on it's own, which may often be short-lived). I personally believe that we often grossly underestimate the effects of supplements on medications, tyrosine's effects on stimulants (and other drugs targeting various types of dopamine-related pathways) are no exception.



• Tyrosine supplements are typically easily metabolized and cleared from the body, lessening potential side effects from residual metabolites (which is the case for several drugs).



• The enzymes responsible for tyrosine metabolism are often dependent on vitamin and mineral nutrients, and can be much more effective if adequate levels of these nutrients are supplied. I have provided a table of some of these key nutrients in a table at the bottom (and top) of this posting.
  

Disadvantages to tyrosine supplementation for ADHD:

• Beneficial responses of tyrosine for ADHD treatment are often short lived (and usually disappear within 2 to 4 weeks, as the body appears to "adapt" or tolerate the higher levels of tyrosine supplementation.



• In most cases, the imbalances of dopamine and norepinephrine are believed to be due as much to the transporters (or agents which shuttle these chemical in and out of the neuronal cells) or receptors (places on the cells where the dopamine or norepinephrine bind). Most ADHD medications (including the stimulants) typically work by blocking, modifying or reversing the modes of action of these transporters in an attempt to restore a proper "inside" vs. "outside" chemical balance. Interestingly, genetics appears to play a role as to the extent of how a certain transporter or receptor functions, and genes may even affect dosage requirements for certain ADHD medications (such as Adderall, or Strattera). In other words, blasting the body with high levels of tyrosine in hopes of using it as a precursor does not necessarily remediate these transporter issues.



• Localization is a problem. Imbalances of dopamine and norepinephrine in ADHD are often seen only in a handful of specific brain regions, so flooding the whole system with tyrosine may not be conducive to zeroing in on these target brain regions. Interestingly, however, the synthesis of monoamine neurotransmitters such as dopamine and norepinephrine may not be tied down entirely to specific brain regions, as there may be some flexibility as to where these chemicals are generated based on the demands (and failures) of other parts of the brain and central nervous system.
  
  
• While side effects may potentially be lower, tyrosine (or L-DOPA) does have some metabolites which can be harmful at high levels. The pro-inflammatory agent homocysteine is one such example, and has been discussed at length in a previous tyrosine for ADHD blog post.



• While anecdotal reports on the benefits of tyrosine supplementation for ADHD treatment abound, the actual number of published studies showing positive results for tyrosine (especially in the last 10-20 years) is surprisingly low.



• As mentioned earlier, tyrosine can "compete" with other amino acids such as tryptophan, valine, leucine and isoleucine for entry into the brain, because they share a similar system of transporters. In fact, there are a number of parallels between the tyrosine to dopamine/norepinephrine pathway and the tryptophan to serotonin pathway, in that they share similar enzymatic processes. In other words, it is possible to create imbalances or reduce the effectiveness of one amino acid (and its desired products of metabolism) if the presence of a competing amino acid is too high. This interference is often seen especially in the tyrosine/tryptophan and can potentially promote imbalances in the serotonin to dopamine ratios.



• Genetic disorders (which are relatively uncommon) or nutrient deficiencies can hamper the efficiency of several enzymes required for tyrosine metabolism. Even being short in one nutrient can cause problems. Given the nutritional status of many with ADHD, this may be a grave problem. As a result, there are numerous opportunities for the tyrosine supplement to be compromised.
  

Ways to improve the effectiveness of tyrosine supplementation for ADHD:

As a blogger on the subject, I always try to remain neutral (many times, however, this can be extremely difficult). When researching the stories and studies on tyrosine supplementation for ADHD, the one thing that continuously caught my attention was the degree of discord between the studies on tyrosine supplementation for ADHD (most of which showed no significant improvement) and the number of clinicians who prescribed it (and individuals who reported benefits from tyrosine). Again, this disagreement may be due to a number of things (differences between study conditions and the treated individuals, co-treatment with ADHD medications, the placebo effect, immediate vs. long-term effects, etc.), so we need to be very careful when making a comparison.

Having said all of this, and weighing everything I've read and researched, I admit (as a blogger) to being skeptical about the overall effectiveness of the whole tyrosine supplementation thing for ADHD. There just don't seem to be enough positive studies grounded in long-term improvements which tyrosine. Nevertheless, the number of positive reports on tyrosine from individuals are too great to ignore in most cases, so an outright condemnation of tyrosine for ADHD is by no means warranted.

It is important to note that none of the studies I've seen (both those supporting or refuting the idea of tyrosine for ADHD) have paid much attention into controlling for the co-factors of the enzymes responsible for metabolizing tyrosine. Just as a reminder, co-factors are essentially vitamins, minerals and other nutrients which are used to help enzymes function properly (or at least more efficiently).

So if we do decide to begin a tyrosine supplementation program, we should make sure we have adequate levels of the following nutrients (I have listed the major nutrients, and where it helps in the tyrosine metabolic processes. It is important to note that this list is not 100% complete, there are several other nutrients which play a role indirectly in the process, but I am just highlighting the major ones I've come across in the studies I've seen on the metabolic pathways of tyrosine to dopamine, norepinephrine and epinephrine):

Here are some links to recommended daily levels of the following nutrients and "cofactors" which can potentially affect the outcome of tyrosine supplementation for ADHD:

• Iron
• Zinc
• Magnesium
• Copper
• Vitamin B6
• Vitamin B12
• Folic Acid
• Vitamin C
• (no official doses have been set for S-Adenosyl Methionine or SAMe, as this can be produced in the body, a ballpark supplemental dose for SAMe is around 100-200 mg twice a day, but of course varies per individual)

A quick summary of this blogger's overall thoughts and advice on tyrosine supplementation for ADHD:

• There are (surprisingly) few well-controlled clinical studies which show tyrosine to be an effective long-term strategy for treating ADHD. In spite of this, tyrosine supplements are often prescribed by a number of physicians (seemingly in a disproportionate manner when compared to other agents with more promising clinical studies). This disparity is at least noteworthy.



• For those (few) studies who do tout the benefits of tyrosine supplements for ADHD, the symptom improvements are often short-lived (often only a few short weeks).



• However, this blogger personally believes that many of the studies may have shown minimal effects due (at least in part) to the fact that many of the other nutritional "puzzle pieces" (such as those given in the tables above) were either neglected or not necessarily in place. These vitamin and mineral-based cofactors can play a huge role in the metabolic conversion of tyrosine to its desired products, and has been discussed at length in the seven previous blog posts on tyrosine and ADHD. Had these studies incorporated some of these co-treatment strategies, some of the results might possibly have been different.



• Please note that while "natural", tyrosine supplementation is not always benign. Health risks, such as amino acid imbalances (due to the competitive nature of several amino acids with tyrosine to get into the brain), cardiovascular issues and even some types of cancers (which are often more associated with a derivative of tyrosine, L-DOPA, however) are very real. Additionally, biochemical side effects of tyrosine metabolism also exist, and can be magnified greatly if rampant tyrosine supplementation is undertaken. The pro-inflammatory agent homocysteine is one such example. However, nutrient-based treatments via B vitamins can often offset a potential homocysteine buildup.



• The dosages for tyrosine supplementation can vary widely ranging from as low as 100 milligrams all the way up to 5000 milligrams (or more, toxicity often begins to set in around 10,000 mg, but this of course widely varies by individual). 2-3 supplements of 500-1000 mg/day is typical in a number of cases (lower doses are almost always a must for children), but dosing should always be under the guidance of a physician.



• Most of the tyrosine supplemental strategies hinge or ride on the theory that ADHD is a dopamine or norepinephrine deficiency issue. However, much of the evidence on the disorder seems to indicate that the transport of these chemical neurotransmitters across neuronal cell membranes and an imbalance of the "inside-the-cell" vs. "outside-the-cell-in-the-gaps-between-neuronal-cell" concentrations of these agents is the real culprit. In other words, flooding the body with tyrosine in hopes that it will generate more dopamine and norepinephrine will not necessarily address this basis of imbalance.



• This blogger personally believes that tyrosine supplementation may be of much greater benefit if used in conjunction with a medication (often a stimulant or other dopamine "releasing" agent). Please note that these supplement-drug interactions may be extremely potent, so please only do this under the supervision of a physician.

In other words, tyrosine supplementation for ADHD treatments is theoretically viable, and has had numerous success stories. Maintaining adequate intake of the nutrient cofactors listed in the tables above helps supply the body's enzymes with the tools they need to metabolize tyrosine most effectively. When dietary intake of these nutrients is sufficient, and tyrosine is wisely used in conjunction with proper pharmaceutical agents, this blogger personally believes that there may be great tangible benefits with regards to ADHD symptoms and treatment.

Do Tyrosine Supplements for ADHD Actually Work? (part 7)

Homocysteine Buildup: The (Potential) Dark Side of Tyrosine and L-DOPA Supplementation for ADHD

Throughout the last six posts on this blog, all of which were concerned with tyrosine supplementation strategies for ADHD, we alluded to the fact that introducing high levels of tyrosine into the body can precipitate a number of other biochemical processes besides the conversion to dopamine and norepinephrine in the brain of the ADHD patient. For reference, I have included the diagram we've been following for the past six blog posts on ADHD and supplementing with tyrosine (you can click on the diagram below and get a larger picture in most browsers):

As we can see, there are a number of enzymes, processes and intermediate steps involved in just this one pathway of tyrosine. Please note that other nutrients, such as ascorbic acid (a.k.a. vitamin C, which has a number of connections to ADHD) and S-Adenosyl methionine (also known as SAM or SAMe, which has also been discussed in greater detail in relation to ADHD elsewhere) are required in this process.

Also, a number of enzymes are required to make this process go.

Here is a quick summary of some of the enzymes used and some of the key vitamins and minerals required (either directly or indirectly) to optimize this enzyme's function:

Tyrosine Hydroxylase: (iron, vitamin C, magnesium, zinc, copper, folic acid or folate, niacin). This is perhaps the most important step of the process, in that it is the slowest or "rate-limiting" step. Because of this, we want to make sure all necessary nutrient "co-factors" (helpers) are in place to help move along this "slow" step as fast as possible)

Dopa Decarboxylase: (vitamin B6, zinc. Also note that excessive levels of some other amino acids, such as leucine, isoleucine, valine, and, especially, tryptophan can compromise this step of tyrosine metabolism. Furthermore, buildup of one of the products of tryptophan metabolism, serotonin, can inhibit or begin to shut down the activity of this Dopa Decarboxylase enzyme and compromise our tyrosine-to-dopamine conversion pathway. This spells bad news if we want to attempt to regulate these dopamine levels in an ADHD brain)

Dopamine Beta Hydroxylase: (vitamin C, but also requires additional antioxidants to "recycle" the used vitamin C)

Phenylethanolamine N-methyltransferase: (S-Adenosyl-methionine or SAMe)

Keep in mind that this list is not extensive. However, the vitamins and minerals are some of the key players in the conversion processes of tyrosine metabolism.

Other Pathways of Tyrosine Metabolism and the Generation of Homocysteine

This is extremely important. A lot of times we get lulled into believing that just because we're using a natural or dietary-based treatment strategy instead of potentially harmful medications, we are immune to negative and/or dangerous side effects typically associated with drugs. However, as a blogger, I urge everyone to reject this idea as quickly as possible. While the side effects as a whole may be a bit more benign or have more room for error for nutrient-based ADHD treatments, going overboard can be just as harmful.

Minerals such as iron, copper and chromium all can be extremely toxic at high levels, and overdosing on certain vitamins (especially the fat soluble ones such as vitamins A and E, which are more difficult to flush out of the system than the water soluble ones), can also be harmful (or even fatal). Even the water-soluble B vitamins can cause problems if overdone (there is a high degree of interaction among most of these, and there is a relatively delicate balance between their levels. Over-supplementing on one, therefore, can greatly compromise the others).

Amino acid supplementation can also be tricky. We mentioned in an earlier posting that chemically similar amino acids often "compete" with each other in areas such as entry into the brain and competition for the same enzymes. As a result, if we go overboard with supplementing on one type of amino acid (such as tyrosine, in the case of ADHD treatment), we need to examine some of the possible repercussions of disturbing the balance of the other amino acids and the products of their metabolism.

Additionally, we need to be aware of other biochemical pathways in the body in which tyrosine is involved. While it may be true that supplementing with tyrosine can boost levels of dopamine and norepinephrine (although the extent of this is debatable, and will be discussed in our final "wrap-up" post), boosting tyrosine intake can result in higher levels some potentially harmful agents such as the compound homocysteine. For this, we will begin by examining the last step of the tyrosine metabolic process (this was covered in the last post in more detail):

Here we see that tyrosine-derived norepinephrine can be converted to epinephrine (adrenaline) in a process which utilizes the enzyme (phenylethanolamine N-methyltransferasePNMT). Even without a chemistry background, we can still see the chemical transformation process above. A methyl (CH3) group was added to the Nitrogen (N) on the right side of the norepinephrine molecule to form norepinephrine. But where does this methyl group come from?

As mentioned in the last post on ADHD and tyrosine, the compound S-Adenosyl Methionine or SAMe, is a very important nutrient in a number of biochemical processes, in that it is able to "donate" (give-up) a CH3 methyl group. This is a relatively rare property among nutrients, and we are just beginning to scratch the surface with regards to the role of this nutrient in treating neurological and psychological disorders such as depression, ADHD and the like.

However, when SAMe does donate it's CH3 methyl group, as in the case above, we are left with homocysteine (please note that there are a few additional steps to go from SAMe to homocysteine, it is not a 1-step conversion process. For simplicity, however, we will not go into these in any further detail. Nevertheless, homocysteine is a major end product of SAMe-related CH3 donor reactions, such as the one given above).

In other words, higher tyrosine (or L-DOPA) levels can make their way to this step of the metabolic process and begin to deplete SAMe levels and lead to high levels of homocysteine. High levels of homocysteine are known as hyperhomocysteinemia, is commonly seen in Parkinson's patients, who often take large amounts of L-DOPA (the second step of tyrosine metabolism in our first diagram in this blog post). Numerous studies have shown that long-term treatment with L-DOPA leads to elevated homocysteine levels in the blood of Parkinson's patients.

Elevated homocysteine levels have been linked from everything from cancer to diabetes to autoimmune disorders to stroke (however, please note that these results are far from unanimous, there are a number of studies showing the contrary for each of the diseases listed. Furthermore, there is still some debate as to whether the high levels of homocysteine are a causal factor for these disorders or just another side effect or symptom of these disorders. Nevertheless, the near-ubiquitous presence of high homocysteine levels in so many diseases across the board should at least suggest that homocysteine-lowering efforts are of great potential benefit, at least in this blogger's opinion).

With regards to ADHD, the actual role of homocysteine is, admittedly, much more murky. While the mechanisms and overall physiology of an ADHD brain vs. a Parkinson's brain show acute differences (In ADHD, chemical imbalances between the "inside" and "outside" regions of a neuron exist, which can be chemically modified via medications which target the proteins which shuttle this neuro-transmitting agents in and out of the cells. In Parkinson's, however, the imbalances are caused by cell death and neuronal degeneration, requiring overall higher levels of neurotransmitters like dopamine need to be supplied via chemical precursor agents like L-DOPA), the fact that the two disorders both share similar treatment methods should (in this blogger's opinion) at least sound a warning bell that some of the negative effects for one might also be prevalent in the other.

Surprisingly, there are very few studies (at least to the best of this blogger's knowledge) on homocysteine levels in the ADHD population, so it is difficult to get a good read on the subject. Nevertheless, given some of the points made earlier on tyrosine or L-DOPA supplementation or treatment and homocysteine buildup, we should at least examine some of the ways to reduce high homocysteine levels. Fortunately (at least in most cases), homocysteine-lowering efforts often respond very well to vitamin and mineral based treatments via supplementation or food fortification. At the center of this are the some of the well-known B vitamins.

B vitamin-based nutritional "weapons" which can combat potentially high homocysteine levels arising from tyrosine or L-DOPA supplementation:

• Vitamin B6 (whose "active" form is known as pyridoxal phosphate. For simplicity, we will just be referring to this compound by its common vitamin name, vitamin B6)
• Cobalamin (a version of vitamin B12)
• Folate (a derivative of Folic Acid or Vitamin B9. For simplicity, as in the diagram below, we will just refer to this modified form of folate as "folic acid", but please note that there is a modest chemical difference here)
  

While the above diagram may look extremely complicated and "busy", please try not to get distracted. The first four "steps" at the top (the arrows simply refer to a metabolic pathway by showing the gradual transformation of one tyrosine-based compound to the next. We have discussed each of these steps in great detail in the previous postings) have already been covered extensively.

The last step, the conversion of norepinephrine to epinephrine was discussed in the last posting on ADHD and tyrosine. The curved arrow simply refers to the fact that the norepinephrine to epinephrine conversion requires another nutrient-based compound SAMe. The norepinephrine essentially "steals" a methyl (CH3) group from SAMe, leaving SAMe to transform into another compound S-Adenosylhomocysteine (which then proceeds to our "dreaded" homocysteine). To put it another way, in order to make the norepinephrine to epinephrine conversion, the valuable nutrient SAMe must be "sacrificed" to a more potentially harmful compound homocysteine.

If this SAMe to homocysteine conversion process is not kept in check, we run the potential risk of homocysteine buildup. However, based on the diagram above (look at the far right side of the diagram for this part), there are 2 different ways to "dump off" high levels of homocysteine by converting it to other more benign compounds. However, each of these two "paths" requires at least one type of B vitamin.

Path #1: conversion of homocysteine to the amino acid cysteine: This is actually a multi-step process, but for the sake of brevity and simplicity, I have left out some of the middle steps. The two major points of note here as follows:

1. This process requires a specific enzyme called cystathione beta-synthase (don't worry about remembering this enzyme, just remember that this enzyme requires a form of vitamin B6 as a cofactor or "helper to function). Thus, to optimize this vitamin B6-based conversion process, we want to make sure that we don't have any deficiencies of this vitamin. Please note that we already mentioned the need for vitamin B6 in another step of the tyrosine supplementation process for ADHD, the conversion of L-DOPA to dopamine. Thus, it is doubly important that we don't come up short on this vitamin.
   
   A rough summary of recommended dosage levels for B6 will be given at the end of this post (Blogger's note: not to go into too much detail here, but this homocysteine to cysteine conversion process is also dependent on another amino acid called serine. I have not included serine as an essential nutrient because serine deficiencies are rare. However, there are some genetic disorders in which serine synthesis is compromised. Seizures and related symptoms are common among those with this genetic defect on serine metabolism).
   
   
2. The conversion of homocysteine to cysteine is (largely) irreversible. This is good news if we want to "dump off" homocysteine levels and not have to worry about the process chemically finding its way back to homocysteine (at least not through this pathway).

Path #2: the conversion of homocysteine to the amino acid methionine: While path #1 is dependent on one type of B vitamin (B6), this pathway is dependent on 2 different B's: a form of vitamin B12 and a derivative of folic acid (vitamin B9). Without going into too much detail, this process requires a methyl (CH3) "donor" (which, in this case, is the modified form of folic acid here. This is very similar to like way the nutrient SAMe acts in helping the conversion from norepinephrine to epinephrine as mentioned earlier).

Please note that, unlike the last case, this process is chemically reversible (which means that the process can go backwards and regenerate homocysteine to a certain extent). This process also requires a special enzyme called homocysteine methyltransferase. Again, don't worry too much about this enzyme, just note that it requires a form of vitamin B12 to function.

To summarize: if we want to keep the "cycle" going to avoid homocysteine buildup by converting homocysteine to methionine, we need 2 different B vitamins: The folic acid as the chemical modifier, and vitamin B12 to help the enzyme involved in the process to function properly.

Perhaps not surprisingly, taking B12 (also known as cobalamin) and a form of folic acid (folate) together has shown to be advantageous in a number of cases. Combinations of folate and cobalamin have also shown to be useful in reducing homocysteine levels in those treated with L-DOPA.

A quick summary on using B vitamins to reduce potential homocysteine buildup from tyrosine (or L-DOPA) supplementation:

• Homocysteine can be an inflammatory compound that is produced indirectly as a result of tyrosine metabolism. High levels of this compound have been linked to a wide number of diseases and health risks.
  
  
• Vitamin B6 can be used to help "shunt" homocysteine to a common (and typically less-harmful) amino acid known as cysteine. This process is (essentially) irreversible. B6 is also a requirement for an earlier step of the tyrosine or L-DOPA metabolic process, the conversion of L-DOPA to dopamine.
  
  
• Vitamin B12 and folic acid can both assist in the conversion of homocysteine to another amino acid, methionine. Unlike the cysteine conversion process above, this process is reversible, meaning that it is possible to "work" backwards towards homocysteine in a bi-directional pathway.
  
  
• Because of the importance of these 3 B vitamin-derived factors in the prevention of homocysteine buildup, it is imperative that we try to avoid shortages of these agents at all costs (but be careful about over-supplementing, B vitamins work best in specific ratios, and overdosing on one can compromise the functions of the other, as we have noted in previous posts on ADHD and nutrient deficiencies).
  
  
• Here are some good sites which list the suggested daily amounts for folic acid (folate), vitamin B6 and vitamin B12. Going slightly higher is often fine (as these agents have relatively high "ceilings" between recommended amounts and toxicity levels), but try to keep the ratio of these different B vitamins as close to the same as in the recommended amounts as possible. Again, please make sure your physician is in the know if you choose to supplement with anything significantly above the recommened levels.

This is our second-to-last post on ADHD and tyrosine. The last one on tyrosine supplementation strategies for ADHD will give a recap of all the key enzymes, nutrients, and chemical intermediates we've covered throughout the past seven postings. It will also provide a summary of what the main studies on exactly how effective tyrosine supplements really are based on clinical studies. Finally, we will briefly mention how tyrosine may be able to augment the effects of common ADHD stimulant medications.