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Depression, 5HTP and L-Tryptophan: Laboratory Markers Matter
CorePsych Updates: Crossroads
March 15, 2010Psychiatric Diagnostic Labels: Functional or Static?
April 17, 2010L-Tryptophan or 5HTP: How Laboratory Markers Can Guide Evolved Treatment
Guest Post: Dr Richard Lord
Guest Post: Dr Richard Lord
Depression Treatment History
Consider the typical progression of a patient with major depression: They usually go through periods of poor appetite and limited food intake, and they systematically show decreases in average stomach acid output. So, their protein intake and digestive capacity become deteriorated. At the same time, they are placed on SSRI therapy that increases their demand for serotonin production. The major catabolic end product from serotonin metabolism is 5-hydroxyindoleacetic acid (5-HIA), which is mainly excreted in urine. {The important point here: 5-HIA [some call it 5-HIAA], the breakdown product from serotonin metabolism, can be measured accurately in the laboratory.}
The Details of Deterioration
The typical patient who has been placed on SSRIs will show levels of 5-HIA that are ~2 times the upper 95% reference limit, or 4-5 times the mean [the breakdown values are significantly elevated in the urine]. That means that the percentage of dietary tryptophan that is flowing into the serotonin pathway is now more like 4-5 times the usual ~10%. Tryptophan as a limiting amino acid, meaning that the amounts found in foods are relatively small in proportion to the other amino acids. When the cells of human tissues need to be replaced, synthesis of thousands of proteins comes to a halt the moment tryptophan is not available.
Neurotransmitter Organ Reserve Matters
Thus, patients with long term major depression can have serious difficulty with maintenance of organ reserve. So, which organs will most quickly show the effects of inadequate ability to maintain reserve? Is it not those that have the greatest turnover and routine demands? And, does that not take us straight to the gut and digestive organs? The parietal cells that make hydrochloric acid, the enterocytes that line the inner surface of the small intestines, and the pancreatic cells that must produce many grams of digestive enzymes daily, lose their ability to keep up with demand.
Treatment Failure: Deeper Cellular Consequences
Thus, it is no wonder that the progression of patients with major depression is so often a downward spiral as more and more drugs are used with less and less efficacy because the ability of their bodies to reverse the major organ reserve loss becomes more and more restricted. The energetic demands of the parietal cells cannot be met because they can’t crank up the rate of mitochondrial enzyme production. The massive daily loss of enterocytes is not matched by new formation of cells at the base of the villi because they can’t supply amino trytophanyl-t-RNA at sufficient rates for ribosomal protein synthesis of everything from calbindin to glutathione-S-transferase. The absence of L-tryptophan alone can produce all of these effects. And, no additional amounts of any other amino acids will help, because the protein synthesis process ceases the moment the ribosome fails to receive a single tryptophan for insertion.
What To Do Next
So, are you going to recommend therapy with large doses of tryptophan for patients on typical SSRI therapy for major depression? No, because you may induce the dangerous serotonin syndrome. This is one of the most challenging nutritional intervention decisions that you will face. A solution that has merit for your investigation is the use of customized free-form amino acid supplement powders based on plasma amino acid profile results. Because of the presence of the full spectrum of amino acids, the large neutral amino acids limit the rate at which blood tryptophan is transferred across the blood-brain barrier. Many clinicians are learning that their patients with major depression (and the frequently accompanying condition of chronic fatigue) respond very positively to this intervention.
Outcome Over Time
Once their organ reserves are restored, they can stop the free-form supplements and go back to dietary protein, or, for an interval, use isolated whey or other superior protein supplements.
Comments on 5-HTP Supplementation
What about the use of 5-HTP as an alternative therapy to support brain serotonin? It can help with mood stabilization. But, does it help with protein synthesis? No, because the conversion of tryptophan to 5-hydroxytryptophan (serotonin) is not a reversible process. So it serves only to slightly spare the loss of tryptophan. What is needed is a consistent increase in available L-tryptophan to drive protein synthesis everywhere, and allow the organ reserve capacity to be rebuilt, – turning the course of the degenerative spiral towards rebuilding of health.
Ed Note
I'm very pleased to share with you this first guest post at CorePsych Blog, written by Dr Richard Lord, Chief Science Officer at Metametrix Laboratories – and teaches at the Metametrix Institute. For those interested in further understanding Laboratory Evaluations see Dr Lord and Dr Bralley's book linked below. These three YouTube videos on Autism will provide an excellent window into Dr Lord's engaging personality and deep insights into specific measurements for treating Autism. I strongly recommend you follow this link over to his presentations on file at Metametrix.
Dr Richard Lord
– Received his BS in Chemistry from Georgia State University, and his PhD in Biochemistry from the University of Texas in 1970. Postdoctoral and staff fellowships were completed at the Clayton Foundation Biochemical Institute (oligopeptide properties), the University of Arizona (insulin self-association), and the National Institutes of Health – Institute of Arthritis and Metabolic Diseases (human thyroid-binding globulin). He served as clinical laboratory director at Horizon Laboratories from 1974-1981, then, for the next eight years, Dr. Lord was Professor and Chairman in the Department of Chemistry for Life University where he was instrumental in the initiation and design of a BS degree in Nutritional Science. Dr. Lord joined Metametrix in 1989 where he currently fills the role of Chief Science Officer.
In addition to co-authoring and editing the books, Laboratory Evaluations in Molecular Medicine and Laboratory Evaluations for Integrative and Functional Medicine, Dr. Lord also publishes technical articles, lectures live at the Applying Laboratory Evaluations to Improve Clinical Outcome Seminars, and consults with health professionals regarding clinical applications of testing for metabolites and toxicants. Dr. Lord has participated in Think Tanks on Orthomolecular Medicine, Environmental Medicine and Autism.
Thanks Richard for this excellent review [emphasis with italics and subheadings my own],
cp
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18 Comments
A very informative and scientific review about 5-HTP and L-Tryptophan, depression is a serious matter for men and women, through this article I found out how 5-HTP and L-Tryptophan helps the medication for a depressed person.
Elsie Frank,
5-HTP
WholeHealth
Speaking of evolved treatment, interestingly, a Lancet study found that Cognitive Behavioral therapy delivered through online IMing and video was found to be more than twice as effective for treating depression compared to in-person visits. The study-leaders hypothesized that it might be easier for patients to remain on their treatment regimen when they could do so via computer; alternatively, therapeutically-supported writing (via IM) may have its own unique therapeutic value.
http://www.Breakthrough.com offers secure online counseling, and clients can see providers licensed anywhere in their state, making for good problem-specialty matching.
Daniel,
Yes, breakthrough is the way of the future for some folks. My policy is to first see them in the office if meds are indicated, – unless we are simply doing the biomedical testing.
cp
Dr. Parker, agreed, esp regarding medication. It’s fascinating, however, the possibilities that open up with web-based counseling itself — not just for clients, who will benefit from the convenience, privacy, and lack of limitation regarding location, but for providers as well, who can open up their market to any state in which they are licensed. There is also the potential of lowering overhead and admin costs, and easing the insurance filing process, while expanding a client base and maintaining a high quality of care.
Doctor Parker,
My 18 yo son has been taking 4 mg of intuniv since December 09. I don’t believe there has been any significant change for the better since he began, actually, I think his attention has become worse. Plus his always tired. He has a terrible time falling asleep at night. Waking up is a nightmare. Now that it’s summertime, he rarely gets up before noon. He is also diagnosed with GAD and depression. His current meds include lithium 1200 mg, effexor 150 mg, adderall xr 20 and 5 mg regular adderall for a kick start. He very much wants to succeed in school and is entering college in the fall.
I wanted to stop the Intuniv in early Spring, but doc and Josh were afraid of what it might do to his schooling, so we waited. Doc recommends titrating down 1mg a week until off. My question to you is, do you agree with this schedule? When we tried to stop the Effexor, it was a nightmare or heroin withdraw proportions.
thanks for your thoughts.
Jean,
With all of the problems he’s having [sleep, nightmares, oversleeping, etc.] it’s inappropriate to speculate about what-to-do next without a much more careful examination. So important for kids going off to school: a good ongoing contact with their primary psych during vacations.
Your doc’s schedule for d/c the Intuniv is completely reasonable – and Intuniv will absolutely not create the problems you experienced with Effexor. They are two completely different drugs with different actions.
cp
Dr. Parker,
My son is currently on a regimen of Focalin XR 15 mg once daily & Intuniv 2 mg once daily. His Neurologist has suggested we try adding Prozac at starting dose of 5 mg to address issues dealing with anxiety. Could you elaborate as to why exactly this should be avoided, as your article mentions, so that I can discuss in detail before we consider adding it to his regimen. Also, have you any experience with “lip licking” on increased dosage of Intuniv (3 mg). A brief trial was instigated but abandoned after my son twice developed a rash around his mouth from compulsatory licking. Thank you for your time & consideration.
KK
KK,
Clearly a problem with MPH products and Prozac, not often reported, but definitely seen in my offices. Prozac interferes with it’s own metabolism making a person feel “Prozac Stupid.” Also take a look at this reference for further info on these interactions if your doc remains unsure – the details are available. Use instead Celexa, low dose, or Zoloft is approved for children and is clean on 2D6 interactions.
On the Intuniv question – yes a tic disorder can arise with Intuniv, not common, but have seen it. My suspicion is that it is glutamate related, and I am watching for the opportunity to do neurotransmitter testing on the next one I see. They are so uncommon I have been waiting. Suggest talking with your doc to lower the dose and go more slowly on short term, with a lower dose.
Summary thoughts: ask about frequency of BM, test for IgG, look for more metabolic slowing downstream from other contributions rather than just straight ADHD.
cp
Dr. P.
You have changed the lives of myself and my children with the education of ADHD and the deeper path beneath it. I have learned so much about integrative medicine and the importance of functional medicine within my personal treatment of ADHD.
It is a journey that I am still on but my eyes are open because of you. My children’s future is changed forever because of the information you have given us. My daughter has headed in the direction of medicine and seeks to attend a university where she can become a D.O. because of you and its integrative medicine that she seeks to learn and practice… All our best wishes with the publication of your new book.
Susan and children
Susan,
Thanks so much for your very kind remarks – you definitely made my day. The real future of psychiatry does live in that interesting interface between mind and body – and so often the brain is the canary in the coal mine. You would have loved the Autism Research Institute meeting in Baltimore – all of the deep biomedical men and women were there – a really interesting international group. I will be posting soon a video of my friend from Cairo, Egypt, and some comments from friends in Brazil and Norway. Very cool place to be – both in practice and geography!
Thanks!
cp
Dr Parker,
i have a 4 year old son who has been using intuniv since it came out in Sept. before that we were on a low dose of Tenex (.5 mg). He was diagnosed with combined ADHD at the age of 3 after severe behavioral problems began to arise. In the beginning we tried stimulants but he metabolized them so quickly followed by extreme impulsivity and anger issues so we took him off of them. The doctor recommended Tenex last summer. Then, we started intuniv. We have tried several different dosages of Intuniv as well as dosing at different times of the day but something is still “off”. For instance, he does fine for a couple of weeks and then has a crash of some sort with sever hyperactivity and tantruming at school. There are instances where you would never guess that he was on meds one day and then the next day he is great and has no problems at home or school . Recently he complained of headache and vomited which i read can be a side effect (while on 3 mg). The neurologist ordered several different blood panels…when the results came back there were markers of inflammation and possible lupus like symptoms. He recommended we see a rheumatologist. Today, again we had a random vomiting episode after a very hyper two days. It is all so confusing that one day he is fine and the next he is so off.
I am concerned that he is having side effects to the medication. He has not one allergy of any kind including food allergies but has not been tested for intolerances. there are other issues such as auditory sensitivity with loud talking, severe exzema, and a horrifying experience where he hemorraghed after a tonsilectomy.
With all of these strange things over the last year and a half, i am at a loss. I have been reading this blog and am interested in what your opinion is about my son.
Thanks!
Amanda,
Your son very likely has significant problems with immune dysfunction, or else he wouldn’t be suffering with “RA or Lupus” at 4 yo. He may not have any food intolerances of the IgE variety, seen, for example, when one eats shrimp and immediately breaks out in hives, -but he very likely has an IgG antibody issue, or some other problem that requires a more biomedical approach. The Narrow Therapeutic Window Response to Intuniv is quite typical of metabolic challenge, and I would jump on it ASAP. One test that may be helpful as a preliminary review: LabCorp has a 96 Food Sensitivity panel #680230 that might show you something. If not stay with that program and there are a number of other tests that can be run to unearth the underlying challenges.
cp
Dr Parker,
Recently had an episode of hallucinations on 3 mg of Intuniv. Have you ever heard of such? Our devel. ped was surprised by it. We also had other issues with 3 mg Intuniv like pica. I still haven’t had the chance to do the bloodwork but i wanted to know if you have ever heard of these issues on Intuniv. thanks amanda
Amanda,
Yes, increasing the glutamate can sometimes bring unwanted tic like symptoms, licking lips, picking etc. Paradoxical, but in evidence. The hallucination thing in children always, repeat that, always drives me hard down the road of immune dysfunction. I can’t begin to tell you the kids I have seen and rather dramatically corrected by chasing down the IgG food allergies and removing the offending food [mentioned in many comments on these postings]. This finding my friends is not snake oil, is clearly in the literature, but will have a hard time finding an audience with psychologically oriented docs who are biased to superficial psych diagnosis.
So, inevitably the first question is: How many times a day does he go #2?
cp
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Jedi,
I must confess you aren’t the first one I’ve heard about with the challenge with Prozac – as you can see it with a quick search here, it remains tops on my least-favorite-psych-drug list. I do however have some suggestions:
1. I will be writing a post soon on the testing available for immune dysfunction – you do need an IgG series, LabCorp has one, #680230 for 96 foods, and that’s just a start. Take a look at the links on this post to Metametrix, as we use them for evolved testing, and I sincerely think we would have a productive outcome chasing down those details with their lab – you can look for the specific IgG4 testing over there.
2. Likely your Prozac problem was encouraged by unknown pre-existing bowel/immune issues. As much trouble as i have had with that medication I can tell you in all fairness, it could easily have been intensely aggravated by underlying immunity issues – been there, seen that.
3. Your neurotransmitters, by just what you have said here, are completely off and could be easily measured and likely could have targeted treatments that very well might turn you around – can’t promise, but is highly likely.
If you are interested in chasing down the details give me a call over at the Services page on the Nav bar, – I do believe we could uncover the other culprits. We can’t reverse what we don’t know. We can significantly reverse what we see thru specific evidence.
cp