Advanced Neurochemistry:

Size: px

Start display at page:

Download "Advanced Neurochemistry:"

Ashlyn Charles
5 years ago
Views:

1 Advanced Neurochemistry: Bridging the Gap between Theory and Application in Neurotransmitter Balancing Lylen Ferris, ND Labrix Clinical Services

2 Does this testing measure brain levels of neurotransmitters? We cannot measure what is in the synapse, but we can test whole body production. i.e. testing cannot tell you exactly how much dopamine is in the brain, but it does reflect whole body levels of dopamine. Neurotransmitter testing is a good general guide to treatment and correlates with symptoms. If you look at the literature, urinary NT testing has considerable validity over the last 20 years or so.

3 Validity of Neurotransmitter Testing Moriarty M, et al. Development of an LC MS/MS method for the analysis of serotonin and related compounds in urine and the identification of a potential biomarker for attention deficit hyperactivity/hyperkinetic disorder. Anal Bioanal Chem. 2011; 401: Kushnir MM, et al. Analysis of catecholamines in urine by positive ion electrospray tandem mass spectrometry. Clin Chem. 2002; 48: Dvorakova M, et al. Urinary catecholamines in children with attention deficit hyperactivity disorder (ADHD): modulation by a polyphenolic extract from pine bark (pycnogenol). Nutr Neurosci. 2007; 10: Koo Loeb JH, et al. Women with eating disorder tendencies display altered cardiovascular neuroendocrine and psychosocial profiles. Psychosom Med. 2000; 62: Audhya T, et al. Correlation of serotonin levels in CSF, platelets, plasma and urine. Biochim Biophys Acta. 2012; 1820: Kaluzna Czaplinkska J, et al. Determination of tryptophan in urine of autistic and healthy children by gas chromatography/mass spectrometry. Med Sci Monit. 2010; 16: Marc DT, Ailts JW, Campeau DC, Bull MJ, Olson KL. Neurotransmitters excreted in the urine as biomarkers of nervous activity: validity and clinical applicability. Neurosci Biobehav Rev Jan; 35(3):635 44

4 How long does my patient need to supplement with amino acids? We recommend supplementing for at least 2 3 months before retesting. Long term support may be necessary for symptom management.

5 Should I retest my patient while she is taking amino acids? Or wait until she stops? It depends on what you are looking for If your patient is doing well and you want to check for therapeutic levels, then have her continue to take her aminos while testing (Just don t take the morning of the test until after the urine sample has been collected). If you are interested in knowing endogenous levels, then stop amino supplements for at least two weeks before testing. Keep in mind that after treatment, your patients might have new endogenous levels.

6 Common Question How will SSRIs and SNRIs effect test results? This will vary for each individual. Most people do not do baseline testing before beginning an SSRI, SNRI, etc. It is generally understood that SSRIs will, over time, deplete serotonin levels. Whitaker, Robert. New Rat Study: SSRIs Markedly Deplete Brain Serotonin. Psychology Today: Mad in America. Published Nov. 1, 2010.

7 How long does it take to metabolize psychotropic drugs? Depends upon the half life of the drug in question Prozac Lexapro Effexor Cymbalta Zoloft 1 16 days hours 5 11 hours 8 17 hours 1 4 days As a general rule, we recommend waiting 6 8 weeks before testing. Over 95 % of a drug is lost or eliminated after 5 halflives. Ritschel, W.A Handbook of Basic Pharmacokinetics, 2nd ed., Drug Intelligence Publications

8 Are results still valid/can you test patients who are using psychotropic drugs? Yes. You will get a snapshot of your patient s imbalances while they are taking the drug.

9 When should I test patients using psychotropic drugs? Recommended to test patients while they are using pharmaceuticals. Caveat: patient must have been taking the pharmaceutical for at least 6 weeks If medication withdrawal is desired, you will be able to support them while they wean.

10 Can patients take amino acids while using psychotropic drugs? Yes. Addressing imbalances can improve their health and symptom picture. If weaning is a goal, addressing imbalances will support them as they transition off of the drug. If using an SSRI or SNRI, can help avoid issues like serotonin syndrome by assessing serotonin levels before adding 5HTP or other serotonin boosting supplements.

11 Is Serotonin Syndrome a real concern? Serotonin syndrome occurs when the patient takes medications or supplements that cause high levels of serotonin to accumulate in the body To be diagnosed, the patient must exhibit at least 3 of the following symptoms: Agitation and restlessness Diarrhea Heavy sweating not due to activity Fever Mental status changes such as confusion Muscle spasms Hyperreflexia Shivering Tremor Uncoordinated movements

12 How long should a patient be off of amino acids before testing? A minimum of two weeks for the patient to reach endogenous levels. Keep in mind, they may have new endogenous levels. Remember that you can test patients while taking aminos. They just need to avoid taking them the morning of collection.

13 How will a methylation deficiency/defect manifest? MTHF is required for the production of tetrahydrobiopterin (BH4), a cofactor in the conversion of tryptophan to 5 HTP and tyrosine to L Dopa. When a defect is present, neurotransmitter levels will likely be lower. Additionally, MTHF is important for MAO and COMT, so if these individuals are supplementing to boost serotonin or catecholamines, levels could be higher than expected because they are not able to break them down as efficiently. The conversion from norepinephrine to epinephrine is a methytransferase.

14 Sample NT Reports with Established MTHFR Defect

15 How much MTHF or methylcobalamin does my patient need? It depends: Does your patient have an established MTHFR mutation? Or do they just need methyl support? Conventionally: Deplin 7.5, 15mg po qd Newer thinking: L methyl folate: 400 mcg qd Methylcobalamin: 1,000 mcg qd Established MTHFR mutations may need more Low B12 status, in the presence of MTHF supplementation, leads to methyl trapping as 5 MTHF cannot donate methyl groups to cobalamin. Low B12 status blocks conversion of MTHF to methionine. Methylcobalamin moves cycle forward to create SAMe and homocysteine.

Why is L theanine mentioned so frequently?

that are running in excess Antagonist of glutamate Can increase serotonin, dopamine and GABA

The neuropharmacology of L theanine (N ethyl L glutamine): a possible neuroprotective and

16 Why is L theanine mentioned so frequently? An incredible adaptogen Can help to boost processes that are sluggish Yet can slow processes that are running in excess Antagonist of glutamate Can increase serotonin, dopamine and GABA levels Acts as a GABA agonist Nathan PJ. The neuropharmacology of L theanine (N ethyl L glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother. 2006;6(2): Weeks BS. Formulations of dietary supplements and herbal extracts for relaxation and anxiolytic action: Relarian. Med Sci Monit Nov;15(11): RA

17 L theanine and symptom management May be useful for reducing high blood pressure Rogers PJ. Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology (Berl) Jan;195(4): Improves memory and attention Park SK, et al. A combination of green tea extract and l theanine improves memory and attention in subjects with mild cognitive impairment: a double blind placebo controlled study. J Med Food Apr;14(4): L theanine and caffeine in combination are beneficial for improving performance on cognitively demanding tasks. Owen GN. The combined effects of L theanine and caffeine on cognitive performance and mood. Nutr Neurosci Aug;11(4): Foxe JJ. Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task. Neuropharmacology Jun;62(7): Can improve cognitive dysfunction in the elderly. Kakuda T. Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction. Pharmacol Res Aug;64(2):162 8.

18 How do omegas help with NT balancing? Increase serotonergic neurotransmission. Vines A, et al. The role of 5HT1A receptors in fish oil mediated increased BDNF expression in the rat hippocampus and cortex: a possible antidepressant mechanism. Neuropharmacology Jan;62(1): Increases serotonin and dopamine levels in rats fed a diet high in DHA. Jiang LH, et al. Pure docosahexaenoic acid can improve depression behaviors and affect HPA axis in mice. Eur Rev Med Pharmacol Sci Nov; 16(13): Protects rat brain function and NT secretion (GABA, 5HT, DA) when exposed to toxins. El Ansary AK. On the protective effect of omega 3 against propionic acid induced neurotixicity in rat pups. Lipids Health Dis Aug 19;10:142. Omega 3 deficiency worsens age induced degradation of glutamatergic transmission. Latour A. Omega 3 fatty acids deficiency aggravates glutamatergic synapse and astroglial aging in the rat hippocampal CA1. Aging Cell Feb;12(1): EPA may be more efficacious than DHA in treating depression. Martins JG. EPA but not DHA appears to be responsible for the efficacy of omega 3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta analysis of randomized controlled trials. J Am Coll Nutr Oct;28(5):

19 How do omegas help with NT balancing? DHA protects dopaminergic neurons Tanriover G, et al. The effects of docosahexaenoic acid on glial derived neurotrophic factor and neurturin in bilateral rat model of Parkinson s disease. Folia Histochem Cytobiol Sep 20;48(3): Omega 3 fatty acids restores dopamine neurotransmission deficits after TBI. Shin SS, Dixon CE. Oral fish oil restores striatal dopamine release after traumatic brain injury. Neurosci Lett Jun 8;496(3): Diets deficient in omega 3 polyunsaturated fatty acids lower dopamine neurotransmission. Narendran R, et al. Improved working memory but no effect on striatal vesicular monoamine transporter type 2 after omega 3 polyunsaturated fatty acid supplementation. PLoS One. 2012;7(10). High cellular membrane DHA content and free DHA in the medium enhance the release of norepinephrine. Mathieu G, et al. DHA enhances the noradrenaline release by SH SY5Y cells. Neurochem Int Jan;56(1): Fish oil supplementation (7.2g/day) blunted epinephrine (and cortisol) secretion in response to mental stress. Delarue J, et al. Fish oil prevents the adrenal activation elicited by mental stress in healthy men. Diabetes Metab Jun; 29(3):

20 Are there any cautions that need to be considered when prescribing amino acid therapy? Uncontrolled HTN and Hyperthyroid Bipolar Avoid L Glutamine and L Tyrosine as they might trigger a manic phase. Hashimoto s/graves May feel jittery on L Tyrosine, L Phenylalanine Low blood pressure Be wary of GABA or taurine Lactating women Be cautious with L dopa (Macuna pruriens) supplementation. (Dopamine lowers prolactin levels.) Start low, go slow your patients should be fine Ongur D, et al. Abnormal glutamatergic neurotransmission and neuronal glial interactions in acute mania. Biol Psychiatry Oct 15;64(8):

21 What drugs can have a negative effect on NT levels? Psychotropic drugs Any medication that depletes co factors H2 blockers, proton pump inhibitors, antacids, antibiotics, Metformin, anti inflammatory drugs, and OCPs deplete folate OCPs also deplete Mg, B6, B12, vitamin C, Zn, Se Proton pump inhibitors and H2 blockers can also lead to deficiencies in B12, vitamin C, Ca, Fe and Mg Heidelbaugh J. Proton pump inhibitors and risk of vitamin and mineral deficiency. Ther Adv in Drug Safe, 2013;4(3): Zengo G. Neurotransmitters & GI Health Testing & Treatment. PracticalCME Medical Training, Accessed 12/10/13

22 My patient has some elevations and some low levels. What should I treat first? This really depends on what is most important for your patient and their individual results and symptom picture. Aim to achieve balance

23 Levodopa Levodopa is a medication that converts to Dopamine. Carbidopa is a medicine (called a decarboxylase inhibitor) that, when taken with levodopa, helps prevent the levodopa from converting to dopamine outside the brain. Decreases side effects caused by increased dopamine levels outside the brain: nausea, vomiting, low blood pressure Enhances effects of levodopa so that lower doses (80% less) are needed to control symptoms Most effective medicine for relieving the symptoms of tremor, stiffness and slowness, and helps improve muscle control, balance and walking. The majority of people taking levodopa develop complications within 5 to 10 years. Dyskinesias: uncontrolled, involuntary movements Elevations in homocysteine Accessibility verified 10/22/14. Accessibility verified 11/17/14.

L Dopa Dosages Usual adult dose for Parkinson s Disease Initial: 250 500mg bid According to drugs.

24 L Dopa Dosages Usual adult dose for Parkinson s Disease Initial: mg bid According to drugs.com, most patients have been adequately treated with mg of levodopa per day, administered as divided doses ranging from 4 8 hours during the waking day. Accessed 10/22/14

25 Macuna vs. L dopa DopaLift: contains 425 mg [standardized to contain 60%Ldopa] per 2 capsules This equates to 255 mg L dopa per 2 capsules Common starting dose of Levodopa is mg bid

26 Macuna vs. L dopa Patient reports taking 2 DopaLift caps (255 mg L dopa) q am x 6 months Patient reports taking Carbidopa/Levodopa (25/100) 6x/day (equals 600mg Levodopa daily)

Baclofen is also a GABA agonist Letter to the editor: Phenibut, the appearance of another potentially

27 Phenibut Concerns about dependence and unresponsiveness Few published cases of negative effects Still, caution should be taken If dependence is an issue, patients given Baclofen to ease withdrawal symptoms Baclofen is also a GABA agonist Letter to the editor: Phenibut, the appearance of another potentially dangerous product in the United States. The American Journal of Medicine. Vol 127. No 8, August 2014.

28 What are the parameters for upper range and lower range? Test Range Lower range Upper range Serotonin GABA Dopamine Norepinephrine Epinephrine Glutamate N/E ratio <10.0 >8.0

29 Pediatric Ranges Test Ages 1 6 Low range Upper range Serotonin GABA Dopamine Norepinephrine Epinephrine Glutamate Test Ages 7 17 Low range Upper range Serotonin GABA Dopamine Norepinephrine Epinephrine Glutamate

Your First Neurotransmitter Reports. Ruth Hobson, ND Staff Physician Labrix

Your First Neurotransmitter Reports Ruth Hobson, ND Staff Physician Labrix Sample NT Test Report Adult Reference Ranges Female 17+ Analyte Range Lower range Upper range Serotonin 52-155 72.6 134.4 GABA