Formerly known as Neuro-Biogenic Amines.

For providers who want a more comprehensive look at neurotransmitter secretion and the metabolism of these markers, consider the Comprehensive Neurotransmitter Profile. This profile includes all of the markers that are part of the NeuroBasic Profile (Serotonin, GABA, Dopamine, Norepinephrine, Epinephrine, Glutamate, Glycine, Histamine, and Phenethylamine), with the addition of the following:

DOPAC: DOPAC is the primary metabolite of dopamine formed via the actions of the MAO enzyme. When DOPAC is elevated and dopamine is low/low range, slowing the activity of the MAO enzyme may help to increase dopamine levels.

3-MT: 3-MT is formed by direct metabolism of dopamine by the COMT enzyme. Very high levels of 3-MT may have stimulant qualities. When 3-MT is elevated and dopamine is low/low range, slowing the activity of the COMT enzyme may help to increase dopamine levels.

Normetanephrine: Normetanephrine is a metabolite of norepinephrine formed via the actions of the COMT enzyme. When normetanephrine is elevated and norepinephrine is low/ low range, slowing the activity of the COMT enzyme may help to increase/maintain norepinephrine levels.

Metanephrine: Metanephrine is a metabolite of epinephrine formed via the actions of the COMT enzyme. When metanephrine is elevated and epinephrine is low/low range, slowing the activity of the COMT enzyme may help to increase/maintain norepinephrine levels.

5-HIAA: Clinically, urinary 5-HIAA is an indicator of serotonin synthesis and metabolism by the MAO enzyme. Some medications as well as dietary consumption of foods rich in serotonin (avocados, eggplant, tomatoes, bananas, melons, pineapple, grapefruit, plums, nuts/nut butters) may elevate 5-HIAA levels. It is recommended to avoid these foods for 3 days prior to sample collection. When 5-HIAA is elevated and serotonin is low/low range, slowing the activity of the MAO enzyme may help to increase serotonin levels.

Tryptamine: Tryptamine is a trace amine derived directly from tryptophan by a vitamin B6-dependent enzyme. Trace amines (tryptamine, tyramine, PEA) may have stimulant effects at high levels. Tryptophan supplementation may increase tryptamine levels. Decreased tryptamine levels may be associated with depression. Tryptamine is normally metabolized by MAO; low enzyme activity may increase tryptamine levels.

Tyrosine: Tyrosine is the amino acid precursor for dopamine, norepinephrine and epinephrine. Low tyrosine levels may increase irritability and lower mood, mental performance, energy levels, body temperature and thyroid function. Tyrosine hydroxylase converts tyrosine into the dopamine precursor L-DOPA.

Tyramine: Tyramine is a trace amine derived directly from tyrosine by a vitamin B6-dependent enzyme. Trace amines (tryptamine, tyramine, PEA) may have stimulant effects at high levels. Foodstuffs such as hard cheeses, chocolates, and red wines contain large amounts of tyramine. Decreased tyramine levels may be associated with depression. Tyramine is normally metabolized by MAO; low enzyme activity may increase tyramine levels.

Taurine: Taurine is an essential amino acid that has an inhibitory effect on neurons; it is important for balancing the action of excitatory neurotransmitters, particularly glutamate. Symptoms of elevated taurine may include apathy, sleep changes, irritability, recklessness, poor concentration, aches and pains, or social withdrawal. Taurine is an ingredient in many “energy drinks.” Decreased CNS taurine synthesis has been reported in individuals with autoimmune and neurodegenerative diseases, including rheumatoid arthritis, Parkinson’s disease, Alzheimer’s disease, and motor neuron diseases such as amyotrophic lateral sclerosis (ALS).

Overview

Symptoms and conditions:

• Depressed mood
• Anxiety
• Adrenal dysfunction
• Fatigue
• Poor sleep
• Loss of mental focus, or cognitive fog
• ADD and ADHD
• Addiction or dependency
• Loss of appetite control
• Compulsive behavior
• Cravings
• Low libido
• Sexual dysfunction

Spot vs 24h Collection - which one should I choose for my patient?

Spot collections have been validated for both first and second morning voids. Collecting the first void of the day provides a medium that can be tested before the impact of stress or foods. This is great news for practitioners testing children and adults who have difficulty continuing to fast until the second void of the day. Additionally, patients experiencing stressful morning schedules due to family matters, commuting, or strenuous exercise may want to consider choosing a first AM void, avoiding potential impact to the catecholamine levels in a second morning void.

Within the field of integrative medicine, the second morning void of urine had been the standard collection method for testing urinary neurotransmitters. The second void has its challenges, however, as patients should refrain from medications, food, exercise, caffeine, nicotine, large quantities of water, and stress before collection of this sample, which can be a challenge for some patients, especially children.

Doctor’s Data has completed in-house studies of spot collections and 24-hour urine collections. It was determined that for most neurotransmitters, the first morning void correlated best with the 24-hour collection. For the NT’s that are directly influenced by diet and daily stressors, one must decide whether it makes sense to identify the trough levels (first morning) or their average over the course of the day. Epinephrine and norepinephrine are especially reflective of stress, and tend to show a higher average in a 24-hour collection than is seen in a first morning collection. This may also be true of serotonin, 5-HIAA and dopamine which can be affected by ingestion of certain foods.

When doing a 24-hour urine collection, ALL urine during a 24-hour period must be collected and accounted for. The total volume is multiplied by the measured concentration. Reference ranges have been determined based on performing a complete 24-hour collection. If the collection is not done correctly, or the volume of urine is not measured correctly, then the results are not valid.

Like many standardized clinical laboratories, Doctor’s Data uses urine creatine to calculate the excreted components in random urine samples. The primary reason for using creatinine for these purposes is that its excretion rate is consistent in patients with normal kidney function, and is an excellent indicator of hydration status of the patient. As such, creatinine is widely used to help standardize the reporting of the measured concentrations of excreted components in urine, and for many analytes has been a suitable and more convenient alternative to collecting a 24-hour urine sample. However, creatinine does have known limitations, including compromised kidney function, where excretion rates are not constant and/or restricted. In such cases, a 24-hour collection is highly recommended.

To summarize:

Spot 1st or 2nd void:

Pros:

Morning baseline collection
One sample
Less influence from environmental stressors and foods

Cons:

Doesn't capture the variability of NTs and metabolites due to daily rhythms or the influence of stress and foods

24 hour urinary NT collection:

Pros:

Allows for the pooling of NTs (average excretion over a day)
Will be reflective of environmental influences of foods and stressors
The only viable option for patients with kidney disease

Cons:

Compliance. Collection of multiple samples over a 24 hour period is likely to result in at least one missed sample, which will skew results
While a first or second morning void is typically adequate for neurotransmitter assessment, in complex cases, it may be helpful to study an individual at a baseline level (first morning) as well as a 24-hour assessment which may better reflect the period of sustained elevation that occurs over the course of the day.

Profile Includes:
Catecholamine Fractionation, free: Dopamine, Epinephrine, & Norepinephrine, Serotonin, Histamine, Amino Acids: GABA, Glutamate,
Glycine, & Phenethylamine (PEA) , Creatinine
5-Hydroxyindolacetic acid (5-HIAA), 3,4-Dihydroxyphenylacetic acid (DOPAC), 3-Methoxytyramine (3-MT), Metanephrine Fractionation: Metanephrine & Normetanephrine, Amino Acids: Taurine, Tyrosine, Tyramine & Tryptamine

Practical

Sample required:

Urine

Average processing time:

21 days

Best Practices for Specimen Collection

2 days before and during collection: Avoid avocados, eggplant, tomatoes, bananas, melons, pineapple, grapefruit, plums, fruit juice, nuts, nut butters, wine, cheese, rice, and chocolate

1 day before and during collection: Avoid strenuous exercise, alcohol, caffeinated beverages, and nicotine products. On the day before and during testing, it is recommended to avoid all supplements and medications until after all samples have been collected (including those that regulate allergy, mood, sleep, pain and inflammation.) Never discontinue prescription medications without consulting your physician.

For patients on psychoactive medications (i.e., SSRIs, benzodiazepines, etc.):

• Many medications can be stopped for the purposes of testing, but psychoactive medications are handled differently. Psychoactive medications should not be stopped suddenly and should be continued as usual the day before collection to ensure results reflect neurotransmitter levels under the influence of these medications. On the day of collection, be sure to take any morning medication doses after the first morning urine collection. (Timing of medication dosing does not need to be adjusted if collecting a 24-hour urine sample.)

• For medications prescribed on an as-needed (prn) basis (i.e., certain anxiety medications): Try to collect urine as far from the last dose of prn prescriptions as possible.

• If tapering off psychoactive medications: Testing can be done during this process to help guide amino acid and co-factor therapy to assist with this transition. Please collect urine between tapered doses - i.e., if one takes medication every other day, test on the day following medication use.

• To test endogenous (levels without the influence of supplements) neurotransmitter levels: It is recommended to wait 6-8 weeks after discontinuing psychoactive meds to test endogenous neurotransmitter levels.

For patients on amino acid or melatonin supplementation:

To test endogenous levels away from the influence of supplements: 

• Because amino acids metabolize at different rates and melatonin can convert into serotonin, both amino acid and melatonin supplementation need to be avoided for at least one week prior to spot urine collection. It is also recommended to avoid supplements throughout the day when performing a 24-hour urine collection.

To test therapeutic levels (to see how supplementation is impacting neurotransmitters):

• Make sure you have been taking supplements daily leading up to collection.

• Ensure at least a 24-hour dosage interval between last dose and time of urine collection. Supplementation can be resumed after AM collection. For a 24-hour urine collection, supplementation should be paused until the collection is completed. 

• Note: It may take 6 months or longer to see improvements in neurotransmitter levels with amino acid and cofactor treatment, whereas symptoms may start to improve as soon as weeks into therapy. Lifestyle and dietary changes are often necessary, along with amino acid and cofactor support, to establish and maintain optimal neurotransmitter balance.

For patients who use recreational substances:

To test endogenous levels away from the influence of substances:

• Ask your provider how long to avoid recreational substances prior to urine collection. Typically, it takes 5 to 7 half-lives for a substance to be eliminated from the blood. 

To test neurotransmitters with current substance use:

• It is recommended to test neurotransmitters as far from the last use as possible. If recreational substance use is infrequent, please check with your provider to determine the best day to test.