Effective Nutritional Intervention for Neurotransmitter Deficiency and Cortisol Excess
The following article was published in the October 2011 issue of The Townsend Letter, and updated for this blog in August 2014, September 2017, and May, 2023.
I have been the director of three clinics in the San Francisco Bay Area that have treated a variety of mood disorders, compulsive eating, and chemical dependency–for over 30 years. In that time, we have provided nutrient therapy to several thousand chronic insomniacs. The careful diagnosis, and the targeted and closely-monitored treatment of the underlying causes of each client’s sleep disorder have led to successful outcomes in almost every case. At least half of our sleepless clients have responded quickly and well to neurotransmitter precursors such as tryptophan or GABA and/or melatonin. Others have required specific cortisol-lowering regimens instead or in addition. These latter cases have tended to involve more severe sleep disturbances and, often, the use of the highly addictive benzodiazepines, the only class of pharmaceuticals in current use capable of temporarily suppressing cortisol levels.
Initial Interviews of Insomniacs
A detailed sleep function assessment has been crucial for our clinic’s ability to determine the course of successful therapy:
- How long have you had a sleep problem?
- Did it begin during or after a particularly stressful time?
- Does insomnia run in your family?
- What time do you get to sleep?
- How long does it take to fall asleep?
- How long do you sleep?
- How often do you wake up in the night? For how long? When?
- Do you need to take benzodiazepines such as Xanax, Ativan, or Klonopin to sleep? Or marijuana? Or alcohol? Or carbs? If so, when?
- Do you have the symptoms of any of the following three types of insomnia?
Type One Insomnia: Serotonin/Melatonin Deficiency
This is the most common cause of insomnia, in our experience: When levels of the extraordinarily and broadly beneficial neurotransmitter, serotonin, are subnormal, there is typically inadequate surplus to use for conversion to melatonin. What results is difficulty in falling asleep (night owl syndrome) which is more common than in staying asleep (though either or both difficulties may be present.) Either way, worries and obsessive or angry thoughts tend to make wakefulness unpleasant. This syndrome can be genetic and longstanding (though the severity has typically increased over time.)
The following is a list of the common symptoms of serotonin deficiency, which helps us rule this syndrome in or out as a cause of the particular insomnia being endured. We ask that it be filled out using a severity scale from 0 to 10.
- night-owl, hard to get to sleep
- disturbed sleep, premature awakening
- negativity, depression
- worry, anxiety
- low self-esteem
- obsessive thoughts or behaviors
- hyperactivity / tics
- perfectionism, controlling behavior
- winter blues
- irritability, anger (e.g., PMS)
- dislike hot weather
- panic attacks; phobias (fear of heights, small spaces, snakes, etc.)
- fibromyalgia, TMJ, migraine
- afternoon or evening cravings for carbs, alcohol, or pot
* The frequent use of benzos is not part of this syndrome.
Re Serotonin Testing: Blood platelet testing for serotonin levels is superior to any testing other than cerebrospinal fluid testing, and almost as hard to find. (Health Diagnostics Lab in New Jersey does provide it.) Blood plasma testing gives a rougher idea of actual levels. Research and practice have convinced us that urinary neurotransmitter testing is extremely unreliable. (See my article on this subject originally published in the Townsend Letter of October 2006 and posted here.
TREATMENT FOR TYPE ONE INSOMNIA: Tryptophan (500 – 2000 mg for adults–less with children), taken when insomnia occurs, e.g., at bedtime and/or in the night, is the first treatment of choice. 5-HTP raises cortisol so we avoid it in serious insomnia cases where hypercortisolemia is often an issue (otherwise nightmares or other sleep deterioration can result.) If tryptophan does not do the whole job, we add melatonin (.5 – 5 mg. or more) as an immediate-release supplement for bedtime and/or in-the-night insomnia.
Re Dosing: We start with the lowest dose and have our clients go up as needed. Children under 14 start with a smaller amount from an opened capsule (mixed with mashed fruit or any other palatable protein-free food, if necessary). The younger and more sensitive the child, the less provided. Sensitive adults should also start with less than one capsule of the lowest dose.
Type Two Insomnia: GABA Deficiency
Gamma amino butyric acid is the brainʼs primary inhibitory (i.e., calming) neurotransmitters. It neutralizes adrenaline as a primary function. A GABA deficiency can accompany a serotonin/melatonin deficiency, or cause sleep problems on its own. Here, muscle tension and other symptoms of overstress interfere with sleep. The following is a list of common symptoms of GABA deficiency which, again, helps us to determine if this syndrome is a significant factor in a particular case of insomnia.
- overstressed or burned out
- unable to relax/loosen up
- stiff or tense muscles
- often feel overwhelmed
- may experience panic attacks
- when resorting to sleep meds, respond best to the benzodiazepines
Re GABA testing: We are not satisfied with any lab testing for levels of this neurotransmitter. (GABA is not found in the platelets and urine testing is especially unreliable when it comes to GABA level testing, with high urinary levels of GABA often found in cases where low GABA symptoms abound and a trial of GABA has immediate benefit.)
TREATMENT OF TYPE TWO INSOMNIA: 100-500 mg or more of GABA taken whenever sleep is a problem can be very helpful along with, or instead of, tryptophan/melatonin. The urine testing labs often suggest that levels of the inhibitory neurotransmitter GABA be enhanced, but do not recommend GABA supplementation itself is mystifying. GABA is often effective at quite low doses (100-500 mg. at bedtime and/or later in the night on awakening) for all over-stressed states, including many cases of insomnia. We do avoid GABA 750 mg, as the reverse syndrome (e.g., anxiety) may develop at such high doses. Clients who do need higher doses, raise them by 500 mg. increasing til they get the ideal dosing. In the few non-responders to GABA, L-theanine provides a very similar calming effect. Dosing: start at 100 mg. theanine and go up as needed.
Type Three Insomnia: High Cortisol
A number of things can raise nocturnal levels of the hormone cortisol temporarily: alcohol or caffeine use and evening exercise among them. (For accurate testing and effective treatment, these factors need to be eliminated.) Excessive stress always raises our levels of the stress-coping giant, cortisol, the chief of our stress-response team (which also includes adrenaline and endorphin.) Chronic stress, e.g., protracted pain or financial, legal or emotional problems, can lead to a permanent hypercortisol state—even long after the precipitating events have resolved. (The chronic GI destress of parasites can cause a high early morning cortisol spike.)
Strangely, this disturbance typically occurs at night, when cortisol levels should be at their lowest. The quality of insomnia is typically an alert “ready to get to work” one or an agitated, hyper-vigilant, or even a panicky one.
Because chronically elevated cortisol suppresses serotonin and exhausts GABA, the worried Type One and tense Type Two Insomnia conditions are a regular, but minor, feature here (and treating them often fails). The balance of this article will concentrate on the less well understood, but increasingly common dynamics of insomnia caused by excessive nocturnal cortisol output.
TESTING NIGHTTIME CORTISOL LEVELS: In addition to the initial sleep status assessment, salivary cortisol testing is critically important–specifically, salivary collections in the night at the time(s) that sleep is disturbed. Without the results of such testing, we cannot be sure if a particular personʼs insomnia is high-cortisol related or not, and should be reluctant to suggest therapy. For the most part we find this to be the most clinically relevant test we’ve ever encountered. Because we are often concerned about daytime as well as nighttime adrenal function, our clinic usually recommends the standard four samples: three daytime samples plus a bedtime (10 – 12PM) sample. We add a 1 – 5AM sample, if early A.M. awakening is a problem. Use bedtime reference ranges to evaluate any samples collected between 10PM and 5AM. Alternatively, you could order one or more single sample cortisol test vials to be used only during the sleepless period(s). Practitioners who cannot order salivary testing may order tests from ZRT Lab through the Canary Club at canaryclub.org. We’ve found ZRT to provide clinically relevant cortisol test results consistent for over 15 years. (But do not assume all other testing, e.g., urinary neurotransmitter testing is useful or that their test interpretation and advice is always helpful.)
LOWERING CORTISOL LEVELS: We start by providing, basic adrenal support using high dose multi-vitamins, multi-minerals, and extra vitamin C to support a blood-sugar stabilizing diet of at least 3 meals, each including at least 25 grams of protein, adequate fat (preferably including saturated fat), and no sugar or other refined carbs. If compliance is a problem, we refer clients to the questionnaires
from my books The Diet Cure or The Craving Cure to identify whether persistent carbohydrate cravings may be due to neurotransmitter deficits, chronic undereating/dieting, food allergy, or yeast overgrowth.
Providing nutrient supplements that specifically lower cortisol: Perhaps 15% of cases of chronically elevated nocturnal cortisol respond well to GABA and/or tryptophan or melatonin. The rest require the nutrients I’ll mention next.
The use of phosphatidyl serine to lower cortisol is advocated by many practitioners. However, we have found that the phosphorylated form of serine (e.g., Seriphos)) has a much stronger cortisol-lowering impact. DiagnosTech Lab’s comparison trials demonstrated this years ago and we’ve confirmed its findings in thousands of cases. Our clinic has used both forms and can attest to the superiority of the phosphorylated form. It is, in fact, one of a very few substances that can permanently subdue really stubborn cortisol elevation after only a few days or weeks of use. Hydrolyzed casein (Lactium) is another supplement we occasionally add. Seriphos (1,000 mg.) one to three capsules per night. Lactium may be used (85 mg) by those who are not casein sensitive, if needed. (See the case studies at the end of this article.)
Cortisol-lowering herbs: Holy Basil can be even more helpful than Lactium, as can Magnolia bark in the combination formula Relora for those who do not benefit from Seriphos. Acupuncture/Chinese herbs for kidney/adrenal treatment should always be considered, especially when cortisol is elevated or subnormal during the day as well as at night.
Avoid supplementation with stimulating, cortisol-elevating nutrients. For example, insomnia caused by high cortisol is not eliminated, but, rather, exacerbated by the use of the stimulating amino acid, l-tyrosine (l-tyrosine converts to noradrenaline and adrenaline.) If indicated by the noradrenalin deficiency symptoms of fatigue or poor concentration, we might recommend tyrosine in the AM only. Typically, we forgo such treatment until after cortisol levels are lowered, and often find that the resulting improved sleep alone restores energy and focus.
The “adaptogenic” herbal mixtures recommended by so many practitioners typically contain Ashwaganda, which can elevate, and licorice, which certainly elevates cortisol. Ashwaganda has proven to often be energizing (and licorice certainly is.) We have found these herbs, even when combined with more calming herbs, to be too stimulating for many of our already hyper and sleepless high-cortisol clients.
Other Cortisol-Normalizing Considerations: For stress reduction/management, the use of caffeine, alcohol, sugar, and other cortisol-elevating drugs as well as excessive dieting or exercise (which also elevate cortisol) may need to be evaluated and addressed.
Where benzodiazepines have been used as regular sleep aids and addiction has resulted, a gradual taper, supported by all of the above nutrients, as needed, and guidance by the Ashton Manual may be required. IVs emphasizing vitamin C (15-25 or more grams) and taurine are helpful on taper days to reduce or eliminate withdrawal symptoms. (IV-administered GABA often has brief adverse effects on breathing.)
Eliminating Disrupted Sleep Associated with Elevated Cortisol: Two Successful Cases
With the proper use of the right tools, the stubborn insomnia caused by neurotransmitter deficiency and/or chronically elevated cortisol can be relieved very quickly. Here are two examples from cases written up by health professionals enrolled in my certification program at The NeuroNutrient Therapy Institute (NNTI).
Case #1 from the practice of Julian Isaacs, PhD, Marin County, California:
VA is a forty-one-year-old single woman with a history of childhood familial psychological abuse. She presents as an intelligent individual who is under considerable stress. She is working a demanding job as well as training to be a nurse. She contacted this office with reference to her sleep disorder.
Her diet was reported as being of good quality and she was not taking any kind of stimulant food or drinks, nor does she drink alcohol. She exercises and lives a stable if very demanding and busy life. She reported highly disturbed nocturnal sleep patterns. Surprisingly, despite disturbed sleep she reported normal energy levels. She was not depressed or significantly anxious in the day. She had trouble with sleep onset, the sleep latency period often being up to an hour or more. But she would also awaken every night in the very early morning (2 – 3 am) and usually be unable to get back to sleep. She described awakenings as being accompanied by “adrenalin rushes”, with accelerated heartbeat, anxiety and hypervigilance. However, she denied cognitive awareness of external threats or fears for body integrity or anxious ruminative content. She had tolerated this condition for two years until being informed by a friend of my amino acid activities.
Her first neurotransmitter deficiency questionnaire suggested needs for tryptophan and GABA for stress, sleep onset and sleep stability. Accordingly, she was advised to take one 500 mg Tryptophan capsule at 4-hour intervals during the day, starting at noon, for stress and three at night, half an hour before retiring, for sleep onset. By her report this reduced stress and shortened sleep onset somewhat. However, the adrenaline rush at nocturnal awakenings continued unabated. She was then advised to take one GABA sublingual tablet (125 mg) prior to going to sleep and immediately after each nocturnal awakening. She did this for a week and then the GABA dose was increased to two tablets after nocturnal awakening, which reduced the anxiety after awakenings somewhat but did not prevent the awakenings nor subsequent insomnia.
It was then determined that her nocturnal awakenings were due to high nocturnal cortisol levels and a trial of Seriphos (1000 mg capsules of Phosphorylated Serine) as a cortisol antagonist at night time. She was advised to take a single capsule at 8pm at night.
She found this process effective the very first night, but asked to modify the dosage to be at bedtime rather than before. This worked even better. She tried doubling the dose for three nights but decided that a single capsule was enough. She continued taking it for a total of three weeks. She then reported that she spontaneously felt sleepy at night at 10.30pm before taking the Seriphos. She was advised to stop taking it immediately and a few days later to try gradually withdrawing the tryptophan, which she did. Happily, she found that both her sleep onset insomnia and awakenings had resolved and have not returned as of our last contact, three months after we began meeting.
Case #2 from the practice of Sabrina Nioche, NNTS, Certified Health Coach, Mammoth, California
M is a 53-year-old male. His sleep problems started when the real estate crisis joined forces with a three-year divorce. This lasting stress took it out of him. He could not stay asleep, plus he felt constantly agitated and his blood pressure was very high. I had suggested GABA several years previously and he had experienced great relief from it then.
This time we combined tryptophan with the GABA in the late afternoon to help prepare for sleep. He repeated the same protocol 30-60 minutes before bedtime. We did not get the desired result so I chose to test his nighttime cortisol levels. At 1:30am his cortisol was through the roof. So we implemented a new protocol of the Seriphos and Lactium combination. He takes 3 Seriphos at bedtime with 2 Lactium capsules. Because Lactium takes effect more quickly, he takes more Lactium if he wakes up in the night. He has not slept this well in years. He texted to thank me after sleeping for 11 hours more recently. He is no longer as tired because he is sleeping. His agitation and blood pressure are problems of the past as well.
Notes on Additional Causes of Insomnia:
- As a possibly Bipolar Spectrum symptom: lithium orotate OTC (5-15 mg 1-3x/day), Lithium carbonate Rx, or Seroquel Rx as needed.
- As a consequence of Pain: d-phenylalanine (500-1000 mg) at bedtime. (See “Amino Acids and Diet in Chronic Pain Management”)
For my Virtual Clinic’s help:
Our staff nutritionists have provided successful nutritional solutions, based on the techniques described here and in The Mood Cure, for more than 20 years. Contact the Julia Ross Virtual Clinic for Insomnia.