Stress & sleep lab package – cortisol, melatonin, neurotransmitters

The cell stress profile measures 8-OHdG (8-hydroxy-deoxyguanosine), 4-hydroxynitrophenylacetic acid, methylmalonic acid and citrulline in morning urine, relative to creatinine. 8-OHdG is formed when reactive oxygen species attack the genetic material and is regarded as a marker of oxidative DNA damage; values in healthy adults depend on smoking, among other things (PubMed 32466448). Methylmalonic acid rises in vitamin B12 deficiency (PubMed 23301732, PubMed 28660890).

4-hydroxynitrophenylacetic acid and citrulline are assigned to nitric oxide metabolism. There are no guidelines for using these urine markers in an individual; they are indications, not a diagnosis.

Cortisol rises markedly after waking and falls over the day; the morning sample about 30 minutes after waking captures this awakening response (PubMed 26563991). In a review, a flatter slope from morning to evening was on average associated with poorer health outcomes, but the association was weak (PubMed 28578301). The laboratory also measures DHEA from the morning sample.

The values apply to the one collection day and depend strongly on keeping exactly to the times (PubMed 26563991).

Melatonin is released at night in darkness; light suppresses its production (PubMed 25908646). It is measured in saliva at 2:00 a.m. How much melatonin a person produces varies greatly by nature: in one study, night-time peak values in saliva ranged from 2 to 84 pg/ml (PubMed 18725972).

A single low value is therefore not proof of a deficiency. Sleep medicine determines the timing of the internal clock with a series of evening samples (PubMed 39158010).

The test measures tryptophan and its breakdown via the kynurenine pathway down to quinolinic acid and NAD, calculates IDO and KMO activity and determines Neopterin, plus serotonin, dopamine, adrenaline and noradrenaline. Around 95% of tryptophan is broken down via the kynurenine pathway, mainly in the liver; cortisol and inflammatory messengers influence this breakdown (PubMed 28469468, PubMed 32153576).

Important: serotonin and the other urine values come from the body, not from the brain (PubMed 32479926).

MicroRNAs (miRNAs) are short pieces of genetic material that control how strongly genes are read. The Stress Monitor determines several miRNAs from one drop of capillary blood, including miR-15a, miR-16, miR-21, miR-106 and let-7, and summarises them in the report.

Circulating miRNAs are being researched as markers of psychological strain. A review found many candidates but hardly any consistent results between studies (PubMed 28673667). They are therefore research markers; there are so far no established cut-offs and no statement for the individual person.

Under strain, the body responds via two systems: the sympathetic nervous system and the adrenal medulla release adrenaline and noradrenaline within seconds; the stress axis of hypothalamus, pituitary gland and adrenal cortex releases cortisol somewhat more slowly. The two systems influence each other (PubMed 8597393). Cortisol also follows a fixed daily rhythm (PubMed 26563991).

Stress and sleep influence each other in both directions: strain activates the stress axis and can disturb sleep, and poor sleep in turn changes the stress response (PubMed 35822937). The internal clock controls melatonin and cortisol in opposite directions; with night work, both rhythms remain largely aligned to the day (PubMed 34969316).

These relationships are well described. How strongly they act in an individual, however, cannot be determined with laboratory values.

The package shows several measures on one to two days. Each has its own limits: cortisol depends strongly on the time of sampling (PubMed 26563991), melatonin varies greatly from person to person (PubMed 18725972), messengers in urine do not reflect the brain (PubMed 32479926), and there are no established markers yet for miRNAs (PubMed 28673667). "Adrenal fatigue" as a cause of exhaustion is not supported by evidence (PubMed 27557747).

Several values together therefore do not make a diagnosis. Their use lies in having measurements for the conversation with the ORY expert team or with your doctor or naturopath, for example from the ORY expert network.

In research, the package's measures are associated with the following complaints, with varying strength of evidence:

• Trouble falling or staying asleep: stress and sleep influence each other via the stress axis (PubMed 35822937). Well described.
• Sleep problems with shift and night work: melatonin and cortisol rhythms hardly adapt (PubMed 34969316). Well established.
• Tiredness and exhaustion: studies on cortisol in exhaustion are contradictory (PubMed 27557747); with inflammation, increased tryptophan breakdown has been observed together with tiredness (PubMed 32153576). Weak evidence.
• Stress load and tension: stress activates catecholamines and cortisol (PubMed 8597393). Well established as a bodily reaction, not measurable for the individual case.
• Drive and mood: dopamine and serotonin contribute to these in the brain (PubMed 23141060, PubMed 32479926); urine values do not reflect this (PubMed 35854107).

These are associations from studies, not causes in an individual person. A laboratory test cannot explain complaints and does not provide a diagnosis. Persistent complaints belong in a medical assessment first.

If you have thoughts of harming yourself or feel you are in an acute crisis: in Germany, the TelefonSeelsorge can be reached free of charge around the clock on 0800 111 0 111. In acute danger, call the emergency number 112.

With loud snoring and pauses in breathing, marked daytime sleepiness or nodding off at the wheel, restless legs in the evening or sleep problems that persist for weeks, the first step is a doctor's practice. For sleep disorders, the European guideline provides for a medical interview with sleep history, questionnaires and a sleep diary, and an examination in a sleep laboratory if other sleep disorders are suspected (PubMed 38016484). A saliva test does not replace this assessment.

If sleep problems come with persistent low mood, anxiety or exhaustion, this belongs in a GP, psychotherapy or psychiatry practice first.

The same applies to signs of a hormonal disorder such as rapid weight gain around the trunk with high blood pressure (PubMed 18334580), severe exhaustion with weight loss and low blood pressure (PubMed 26760044) or sudden bouts of a racing heart with sweating and high blood pressure (PubMed 24893135). Chest pain, shortness of breath or circulatory collapse are an emergency: call 112.

This page does not give treatment recommendations. Whether a result means anything at all and which steps make sense depends on your overall situation: complaints, previous findings, medication, sleep and stress. For sleep disorders, the European guideline names cognitive behavioural therapy as the first-line treatment (PubMed 38016484); that complaints can be steered via individual laboratory values is not supported by evidence.

What makes sense for you belongs in a conversation with the ORY expert team or with your doctor or naturopath, for example from the ORY expert network. Do not take preparations that influence messengers or hormones on your own because of a laboratory value, especially not alongside prescribed medication.

According to the instructions, no antibiotics for at least 4 weeks and no probiotics for at least 2 weeks beforehand. Each of the five analyses has its own instructions in the kit; complete the request form in advance and lay out all tubes in the order of the schedule. The samples are spread over one night and the following day:

• Night, 2:00 a.m. – melatonin: in the dark, before brushing your teeth or at least 30 minutes afterwards, no food and no mouthwash in the 30 minutes before. Rinse your mouth with water, let saliva flow passively until the tube is half full without foam; store in the fridge (2–8 °C).
• Morning – urine for the cell stress profile and the neurotransmitter test, exactly as described in the enclosed instructions.
• Approx. 08:00 – morning cortisol: about 30 minutes after waking, fasting, before breakfast and coffee.
• Approx. 10:00 – capillary blood: wash hands with warm water, prick the side of the fingertip, wipe away the first drop, do not squeeze, soak the circles of the collection card and let it dry for 15–20 minutes.
• Approx. 12:00 – midday cortisol: at least 30 minutes after eating or drinking, no smoking in the 30 minutes before.
• Approx. 20:00 – evening cortisol: at least 30 minutes after dinner.

Put all samples with the request form in the prepaid shipping bag and post it the next morning, only Monday to Thursday, not on Fridays or before public holidays. State cortisone and hormone-containing medication on the request form; only pause prescribed medication after talking to your doctor.

The analysis usually takes 7–21 days from the time the sample arrives at the laboratory. As soon as the report is ready, you will be notified. The 10-minute results consultation with the ORY expert team is included in the price.

The stress axis & sleep-wake rhythm lab package costs €762 including VAT, shipping, return postage and results consultation. Ordered individually, the five analyses cost €955 together.

Statutory health insurance in Germany generally does not cover laboratory analyses you order yourself. With private insurance, reimbursement may be possible; how it works is described under "Reimbursement by private insurance".

The package (€762) contains the cell stress profile (€165), the cortisol day profile (€155), the melatonin test (€55), the neurotransmitter tryptophan metabolism test (€305) and the Epigenetics Stress Monitor (€275). If you only want to measure one area, you can order the analyses individually; for serotonin and catecholamines alone there is Neurotransmitter Basic (€105).

Which scope makes sense for you can be clarified in the free initial consultation.