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Organix Step 3: Neurotransmitters

Neurotransmitters are the body’s chemical messengers. The Organix test looks at the activity of four important ones that influence our energy levels, response to stress, mood, sleep patterns and weight regulation. Just like we determine the efficiency of a car’s engine by measuring the exhaust, we measure the function of these neurotransmitters by measuring their metabolites, or breakdown products, in urine.

The Stress Neurotransmitters: Norepinephrine, Epinephrine, and Dopamine

When we encounter a stressor, our body produces norepinephrine and epinephrine that stimulate our “fight or flight” or stress response. The by-product in urine is vanilmandelate (VMA). Dopamine is also involved in the stress response as well as in memory, movement and mood, and its by-product is homovanillate (HVA).

Figure 1

Low levels of these metabolites have been associated with low levels of these neurotransmitters in the central nervous system manifesting in symptoms such as depression, sleep disturbances, anxiety and fatigue. Supplementing with the precursor, tyrosine, will insure proper levels needed to make these neurotransmitters. In addition, low levels of VMA and HVA can indicate poor adrenal function, as these are also made in the adrenal medulla. Addressing stress, and supporting adrenal function with vitamin C, B-vitamins and herbs such as ginseng and ashwaganda may also improve levels.

High levels of VMA and HVA reflect a higher-than-normal turnover of these neurotransmitters due to a chronic stress response, elevated cortisol, or drugs such as caffeine, ephedra, pseudoephedrine and cocaine. Neuroblastic tumors can also cause a profound elevation in VMA. Stress management techniques, reduction in use of neuro-stimulating drugs, and addition of calming herbs and nutrients such as rhodiola, GABA, glycine or theanine, have all been used effectively to reduce levels of these neurotransmitters. If VMA levels are very high in relation to HVA, a workup to rule out tumor growth may be indicated.

The Mood Neurotransmitter: Serotonin

Serotonin is considered the “happy” neurotransmitter as it regulates mood, satiety, and sleep. 5-Hydroxyindoleacetate (5-HIAA) is a urinary metabolite of serotonin. Low levels of 5-HIAA represent low levels of circulating serotonin, and can manifest in symptoms such as depression, mood disorders and sleep disturbances or insomnia. Simple supplementation of 5-hydroxytryptophan or tryptophan or increased intake of tryptophan rich foods such as turkey, bananas, lentils, walnuts or eggs can help support the body’s production of serotonin to correct the low level.

High levels of 5-HIAA can occur in patients who are on 5-hydroxytryptophan, or tryptophan. Dietary intake of the tryptophan-rich foods the night before the urine collection can also mildly elevate 5-HIAA levels.

Selective serotonin reuptake inhibitors (SSRIs), which are used as anti-depressants, can also increase urinary 5-HIAA excretion. 5-HIAA is actually a good measure of the effectiveness of the SSRI. If your patient is taking an SSRI and 5-HIAA is low, it can mean that the patient is a “non-responder” to that SSRI—meaning there simply isn’t enough serotonin to make the SSRI effective.

Very high levels of 5-HIAA can be a sign of a carcinoid tumor when dietary tryptophan supplementation is ruled out. A 24-hour urinary 5-HIAA is recommended in cases like this.

The Kynurenin Pathway

Tryptophan, in addition to making serotonin, is the parent compound in the Kynurenin Pathway (see figure below). This pathway is very active in the liver and is the way that our bodies make niacin, a B-vitamin.

This pathway is also active in the brain as a way to fight off pathogens such as viruses or bacteria. These pathogens stimulate an inflammatory response by the body and this pathway becomes activated. Quinolinate, a member of this pathway, interacts with NMDA receptors of glutamatergic neurons in the brain and stimulates the release of glutamate—an excitatory neurotransmitter. The actions of quinolinate are responsible for the symptoms we experience when we have the flu, such as achy muscles and sensitivity to light and sounds. Chronic stimulation of this pathway can lead to glutamate excitotoxicity and can cause the neurons to degenerate.

Ultimately, the best solution for reducing the production of quinolinate is to identify the underlying cause of the inflammatory response such as viral infection, parasite infection, bacterial infections, or possibly food sensitivities. In the meantime, supplementing with magnesium and glycine can reduce the damaging effects of quinolinate.

The analytes kynurenate and picolinate are also a part of this pathway. They typically rise in concert with quinolinate when there is an inflammatory response. If kynurenate is elevated by itself, it becomes a marker of vitamin B-6 deficiency as does its partner, xanthurenate which we talked about in the B-vitamin status section.

Figure 2

In conclusion, the neurotransmitter section of the Organix profile provides valuable information about your patient’s response to stress and how he can improve mood, energy level, sleep and anxiety. It also gives insight into the patient’s inflammatory response and underlying viral or bacterial burdens.

We've reached the half-way point! Next week we'll move on to Step 4 of this great test.

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Comments (14) -

Christine
Christine Canada
6/23/2010 7:04:34 PM #

Hi, is there a link between high levels of kynurenate, low levels of B6, chronic depression and addictions (drugs, alcool and sex)...  

Thanks

Christine

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Cass Nelson-Dooley
Cass Nelson-Dooley United States
7/7/2010 12:36:44 PM #

Yes, vitamin B6 is important in the treatment of neurological disorders and kynurenic acid may explain that effect. Kynurenic acid is a glutamate receptor antagonist and it is elevated when there are insufficient vitamin B6 levels. High kynurenic acid has been implicated in the pathogenesis of schizophrenia. Clinical improvement has been seen with vitamin B6 supplementation in cases of depression, ADD, and schizophrenia (Gaby, Wright 2007). Because B6 is important for neurotransmitter synthesis and catabolism, it could also be very important in addictions, where neurotransmitters may be abnormal.

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Kimberly H.
Kimberly H. United States
8/21/2012 9:05:11 PM #

Hit a wall with 37yo, f, sensitive to everything. Great presentation, but still looking for answers.Elevated HVA, very low 5hia. Low Quin, moderate Xanth & Kynur. So, inflammation not the problem? Adverse reactions to SSRI, 5htp, L- Tryptophan. Nueroscience showed normal urine Serotonin & low 5hia. Cannot bring 5hia up. Severe anxiety, depression. B vits were all -DL* or very elevated ,but cannot tolerate them. Adverse to Methyls/co-factors, Vit C, etc.. OAT did show dysbiosis, but reacts to probiotics. What else can I look for in results that may help identify issue with Serotonin utilization & breakdown?  Or possible alt test?  Thanks so much.

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Kim H.
Kim H. United States
8/22/2012 9:40:37 AM #


If Kynurenate and Xanthurenate are in 3rd quntile and Picolinate in 4th quintile, would that indicate a B6 need? I suspected inflammation, but the Quinolinate is low. I ask because this person cannot tolerate any B's right now, esp active form.
Could this explain a very low 5hia? This person also cannot tolerate 5 htp or Tryptophan supplements.
Thanks.

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Kim H.
Kim H. United States
8/22/2012 12:21:07 PM #

Sorry for the double post. It had appeared the first did not go though, but I see that it did.

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AK
AK United States
12/5/2010 10:06:08 PM #

Some of these metabolites have large reference ranges spanning an order of magnitude.

Homovanilinate for example... Can a low but still in reference range level still be causing significant symptoms?

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Nathan Goodyear
Nathan Goodyear United States
12/6/2010 9:48:38 AM #

look at the other co-factors to get a better idea of the trend ie  tetrahydrobiopterin, Cu, B6...  When these are low and the metabolites are low normal, the clients will need therapy.  You are just catching them early or with a mild imbalance.

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Eve Bralley
Eve Bralley United States
12/14/2010 12:29:55 PM #

AK, please view our presentation on reference ranges and how to interpret them.  www.metametrix.com/.../how-to-read-metametrix-laboratory-reports-reference-ranges.  When looking at the results, you take the values along with patient symptoms to determine treamtments.  

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Eve Bralley
Eve Bralley United States
12/14/2010 1:12:40 PM #

Good point Nathan.  The cofactors are important to look at when determining treatment for these analyte imbalances.  Thanks for the comment!

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Kathleen Pisani
Kathleen Pisani United States
1/29/2011 5:07:41 PM #

Hi, I was just wondering about a couple of things. First, how does phosphitydle serine play into the neurotransmitters? I know that it helps lower cortisol, but I don't know how it does that or what else it does. IT seems to ease my ADD symptoms. Also, I am wondering if organix give indications of vit a and d absorption?
Thank you.
Kat

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Barb
Barb
8/12/2012 4:43:21 PM #

Well presented. That was just the kind of motivation I needed on it.

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cnelsondooley
cnelsondooley United States
8/23/2012 2:02:46 PM #

Kathleen,

Phosphatidylserine is important in the lipid membrane for a number of functions. See section 3 on phosphaytidylserine's biological function on this site:
http://lipidlibrary.aocs.org/lipids/ps/index.htm

A healthy lipid bilayer in all cells, especially the nervous system, is critical for neurotransmitter signalling. Some sources have said that phosphatidylserine can ameliorate the effects of elevated stress hormones. Metametrix doesn't offer testing for phosphatidylserine but tests looking at amino acids (serine, ethanolamine, phosphoethanolamine) and adrenal health may indicate the need for phosphatidylserine support.

Thank you for your comment!
Cass Nelson-Dooley, MS

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Annie
Annie United Kingdom
11/22/2012 8:24:05 AM #

Hi if 5 hydroxyindoleacetate and kynurenate is high this points to a need for B6 and possibly Tyrosine.  However the breakdown of seratonin (as a stress response) is depeleting the reserves - would the patient benefit from supplementary 5 HTP? Many thanks for any assistance.

Reply

cnelsondooley
cnelsondooley
12/6/2012 1:34:09 PM #

Annie,
We generally interpret high 5-hydoxyindoleacetate (high serotonin turnover) to indicate that there is excess serotonin. The clinician may want to remove causes of stress or gut imbalance that might lead to high serotonin. Of course clinicians are encouraged to interpret the test results as they see fit, based on what they know about the patient's presentation and history. Some clinicians might choose to supplement with 5-HTP when serotonin turnover is high, but it is not the usual approach.
Thanks for your comment!
Cass Nelson-Dooley, MS

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