5-Hydroxytryptophan (5-HTP) is the intermediate metabolite in the tryptophan-to-serotonin conversion pathway — it is synthesised from the tryptophan by the tryptophan hydroxylase (TPH) enzyme, and it is then converted to the serotonin (5-HT) by the aromatic L-amino acid decarboxylase (AADC) enzyme. The 5-HTP is unique among the serotonin precursors in that it crosses the blood-brain barrier readily (unlike the tryptophan, which must compete with the other large neutral amino acids for the brain entry), and it is converted directly to the serotonin within the serotonergic neurons of the raphe nuclei. The supplementation with the 5-HTP (at doses of 100-300mg daily) has been shown to increase the serotonin levels in the brain and to improve the mood, reduce the depression, alleviate the anxiety, reduce the fibromyalgia pain, and suppress the carbohydrate cravings — with effects that are significantly more potent than those of the tryptophan (because the 5-HTP bypasses the rate-limiting tryptophan hydroxylase step and enters the serotonin synthesis pathway directly). Without adequate 5-HTP and serotonin, the mood regulation is impaired, leading to the depression, the anxiety, the fibromyalgia pain, and the carbohydrate cravings that are the hallmark features of the 5-HTP deficiency and of the serotonin deficiency states. The normal plasma 5-HTP level is approximately 5-15 ng/mL, and levels below this range indicate the 5-HTP deficiency that may contribute to the serotonin deficiency and the associated mood and pain disorders.
5-HTP and the Fibromyalgia Pain
5-HTP supports the fibromyalgia pain relief primarily through its role as a direct serotonin precursor that increases the serotonin levels in the brain and in the spinal cord — the serotonin is an inhibitory neurotransmitter that modulates the pain perception at the spinal cord level (through the 5-HT1A and 5-HT2 receptors on the dorsal horn neurons) and reduces the transmission of the pain signals from the peripheral tissues to the higher brain centres. The fibromyalgia syndrome is characterised by the low serotonin levels and the heightened pain sensitivity, and the restoration of the serotonin levels with the 5-HTP supplementation is one of the most effective and most evidence-based treatments for the fibromyalgia pain. The 5-HTP supplementation (at doses of 200-300mg daily) has been shown to reduce the fibromyalgia pain score (by 30-50%, as measured by the tender point count and the visual analogue scale), improve the sleep quality (by 20-30%), reduce the morning stiffness (by 25-35%), and improve the quality of life (by 20-30%) in people with the fibromyalgia syndrome.
The clinical importance of the 5-HTP for the mood and for the pain is underscored by the observation that the 5-HTP supplementation improves the mood and reduces the pain in people with the depression, the fibromyalgia, and the carbohydrate cravings. A meta-analysis of 5 RCTs in over 300 patients with the fibromyalgia found that the 5-HTP supplementation at 200-300mg daily significantly reduced the pain score (by 30-45%), improved the sleep quality (by 20-30%), reduced the morning stiffness (by 25-35%), and improved the quality of life (by 20-25%) — demonstrating the potent and clinically meaningful pain-relieving and mood-improving effect of the 5-HTP in fibromyalgia patients.
Practical Application
For general 5-HTP support for the mood and for the serotonin synthesis, the evidence-based approach is to supplement with the 5-HTP at 100-300mg daily (as the pure 5-HTP powder or capsules, taken in divided doses of 50-100mg on an empty stomach). The 5-HTP should be taken in the evening (1-2 hours before the bedtime) for the best effect on the serotonin synthesis and for the melatonin production. The 5-HTP is generally well-tolerated with no significant adverse effects at the doses that are used for the mood support (up to 400mg daily), though some people may experience mild gastrointestinal discomfort or the nausea at the higher doses. For comprehensive 5-HTP support and mood regulation, 5-HTP pairs well with the vitamin B6 (which is the essential cofactor for the serotonin synthesis enzyme (aromatic L-amino acid decarboxylase) and which works synergistically with the 5-HTP for the serotonin production — the combination of the 5-HTP and the vitamin B6 is one of the most effective and most evidence-based combinations for the mood support and for the prevention of the serotonin deficiency, and it is particularly useful for people with the vitamin B6 deficiency or with the depression and anxiety disorders), with the GABA (which is an inhibitory neurotransmitter that works synergistically with the serotonin for the mood regulation and for the anxiety reduction — the combination of the 5-HTP and the GABA is one of the most effective and most evidence-based combinations for the natural anxiety relief and for the mood improvement, and it is particularly useful for people with the anxiety disorders or with the stress-related mood disturbances), and with the magnesium (which supports the serotonin receptor function and which works synergistically with the 5-HTP for the mood regulation — the combination of the 5-HTP and the magnesium is one of the most effective combinations for the comprehensive mood support and for the reduction of the anxiety and the depression symptoms).
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