• Griffonia
    Griffonia
  • Griffonia
    Griffonia

5-HTP

L-5-HYDROXYTRYPTOPHAN

DMF

Linnea extracts and manufactures 5-HTP as a botanical ingredient for pharmaceutical purposes.

In investigations into the causes of neuropsychiatric disorders, sufficient evidence has been found to support the theory whereby an unbalanced metabolism of amino acids, and Serotonin in particular, plays an important role in causing these disorders. In fact, these substances are present in a reduced quantity in the brain tissue of depressed patients and in some neurological syndromes their rate of metabolite production is low.

Since exogenous Serotonin cannot be used, it must be synthesized at the sites where it acts from the amino acid precursor, Tryptophan. Only 1% of exogenous Tryptophan is however transformed into Serotonin. A natural alternative is the use of the food supplement L-5-Hydroxytryptophan (5-HTP), that is the direct Serotonin precursor in the brain. It passes through the blood/brain barrier easily and acts by providing more of the basic raw material the body needs to metabolise Serotonin and thus raise Serotonin levels.

Source

5-HTP is extracted from the seeds of the Griffonia tree, which belongs to the Fabaceae family and grows principally in West Africa.

Griffonia simplicifolia is a woody climbing shrub native to West and Central Africa where it is found mostly in thickets, usually near mounds of the termite Macrotermes, on plains, in forests, in secondary vegetation and on old farms. Griffonia simplicifolia is an extremely adaptable evergreen plant that produces fairly large quantities of highly palatable herbage of good nutritive value and large, viable seeds.

Traditionally, Africans use different parts of the plant for different purposes. The stem and roots are used as chewing sticks that aid wound healing whilst leaf juice is used as an enema and in the treatment of kidney ailments. A decoction of stems and leaves is also used to stop vomiting, to treat congestion of the pelvis and as an aphrodisiac. Griffonia simplicifolia seeds are carefully harvested through a selected network of suppliers. Every shipment leaving West Africa is inspected previously by a Linnea representative in situ so as to ensure raw material of the highest quality all over the world.

Activity

5-HTP is the precursor in the biosynthesis of the neurotransmitters Serotonin and Melatonin from Tryptophan. While Tryptophan has a general effect on the whole body, 5-HTP crosses the blood-brain barrier easily, skips the hydroxylation phase, which is obligatory for Tryptophan, and is completely transformed into Serotonin by 5-hydroxytryptophan decarboxylase (present in nervous and liver tissue) [1].

Serotonin is an important neuromediator in the modulation of several specific activities at the CNS level, including control of the pain threshold, regulation of sleep patterns, the activity of the neuroendocrine pituitary gland, the motor integrating mechanisms of the extra-pyramidal system and neuronal excitability. It is also involved in thermal and eating regulation and the control of sexual and aggressive behaviour [2].

Common Applications and Evidence

Common Applications

5-HTP is a nutritional supplement used principally to maintain sleeping patterns, lighten moods (anxiety, depression) and treat obesity-related binge eating [1,3]. It has also been found to be effective in relieving the symptoms of several diseases such as fibromyalgia, premenstrual syndrome, attention deficit disorder and chronic headaches [4].

Clinical Evidence

Depression

Considering the major role of Serotonin in depression and 5-HTP in Serotonin synthesis, 5-HTP has been used for a long time in Europe as an alternative anti-depressant [5]. The antidepressant efficacy of 5-HTP has been studied in more than 900 patients treated with doses ranging from 50 mg/day to 600 mg/day for a period of 4 weeks to 8 months and most of them found 5-HTP superior to the placebo. A number of open-label studies have also been conducted in comparison with other active substances [2]. 5-HTP was found to be effective in reducing depression scores (on the Hamilton’s Rating Scale for Depression, Zung’s Depression Status Inventory, Clinical Global Impression Scale, Mini Mental State Examination, etc.) and in reducing mild-to-moderate depression with the advantage of giving fewer side effects than conventional anti-depressants. 5-HTP supplementation is thus considered a possible significant addition to the antidepressant armamentarium [6,7,8].

Migraine, headache and other pain syndromes

Many Authors in the past have demonstrated that Serotonin plays a role in mitigating migraine attacks. They found that the plasma levels of Serotonin were significantly reduced during the attack while its main metabolite 5-HIAA (5-Hydroxyindoleacetic Acid) was excreted in increasing quantities in the urine. Serotonin and its precursor 5-HTP also act as analgesics [1,9]. It has been postulated that both a reduction in Serotonin levels and a malfunctioning of the antinociceptive system are involved in causing migraine. Clinical experience with 5-HTP in migraine is based on several trials conducted on more than 400 adult patients for a period of 6 weeks to 24 months and on more than 150 paediatric patients (aged 6-14 years) for 6 weeks to 3 months [9,10]. In all open-label trials and placebo-controlled trials, treatment with 5-HTP was shown to significantly improve the symptom scores (migraine index, pain score, etc.), reducing the frequency and severity of the headache. Almost 74% of patients were considered as responders to treatment with an improvement in the symptoms in 86% of cases. A study conducted for the Portuguese Headache Society also demonstrated that 5HTP is an effective prophylactic treatment for chronic tension headaches and juvenile headaches that does not cause the adverse reactions often associated with similar drugs [11].

Sleep disorders

Serotonin, like other neuromediators, is involved in the regulation of hypnotic activity. The duration and quality of sleep and its REM phase are also influenced by the activity of Serotonin [12]. Several studies conducted on adults and children have shown that 5-HTP, thanks to its role in the synthesis of Serotonin and Melatonin, has a positive effect on the regulation of sleep patterns. The doses tested ranged from 300 mg to 100 mg and the lower dose seems preferable since, according to anecdotal reports, higher doses tend to cause vivid dreams or even nightmares [13,14].

Obesity

Clinical studies demonstrate that serotonergic drugs specifically reduce appetite prior and subsequent to the consumption of fixed calorie loads, and also reduce pre-meal appetite and calories intake during ad libitum meals. Significant weight loss in obese patients has been observed in treatment with 5-HTP for two consecutive 6-week periods with or without diet prescription. A reduction in carbohydrate intake and early satiety were also reported. These findings together with the high tolerance observed suggest that 5-HTP may be used to treat obesity safely [15,16].

Technical Description
Name of the plant Griffonia simplicifolia
Part of the plant used Seeds
Formula C11H12N2O3
IUPAC Name L-5-Hydroxytryptophan
Synonyms Oxitriptan, 5HTP, L-Amino-3-(5-Hydroxy-1H-indol-3yl) propionic acid
Molecular Weight 220.2 g/mol
CAS N. 4350-09-8

Structural Formula
5 HTP

Bibliografic References
  1. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Alternative medicine review : a journal of clinical therapeutic 3 (4): 271–80 (1998). Birdsall TC.
  2. Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan. Pharmacol Ther. 109(3):325- 38 (2006). Turner EH, Loftis JM, Blackwell AD
  3. Monoamine precursors in the treatment of psychiatric disorders. In: Wurtman RJ, Wurtman JJ, eds. Nutrition and the Brain. New York: Raven Press :89-139 (1986). van Praag HM, Lemus C.
  4. Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. J Int Med Res. 18(3):201-9. Caruso I, Sarzi Puttini P, Cazzola M, Azzolini V.
  5. Management of depression with serotonin precursors. Biol Psychiatry 16: 291–310 (1981). Van Praag HM.
  6. 5-Hydroxytryptophan (5-HTP) and a MAOI (nialamide) in the treatment of depressions. A double-blind controlled study. Int Pharmacopsychiatry. 11(1):8-15, (1976). Aliño JJ, Gutierrez JL, Iglesias ML
  7. The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study. Arch Psychiatr Nervenkr. 224(2):175-86 (1977). Angst J, Woggon B, Schoepf J.
  8. Second-tier natural antidepressants: review and critique. J Affect Disord. 130(3):343-57 (2011). Iovieno N, Dalton ED, Fava M, Mischoulon D
  9. Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. J Neurosurg Sci ;29(3):239-48 (1985). De Benedittis G, Massei R
  10. L-5HTP treatment in primary headaches: an attempt at clinical identification of responsive patients. Cephalalgia 4(3):159-65 (1984). Bono G, Micieli G, Sances G, Calvani M, Nappi G
  11. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebocontrolled study. Headache. 40(6):451-6 (2000). Ribeiro CA.
  12. Effect of 5-hydroxytryptophan, a serotonin precursor, on sleep disorders. Ann Med Psychol 1:792-798 (1977). Soulairac A, Lambinet H.
  13. Clinical studies of the effect of the serotonin precursor, L-5- hydroxytryptophan, on sleep disorders. Schweiz Rundsch Med Prax. Aug 23;77(34A):19-23 (1988). Soulairac A, Lambinet H
  14. Headache in association with sleep disorders in children: a psychodiagnostic evaluation and controlled clinical study--L-5- HTP versus placebo. Drugs Exp Clin Res. 13(7):425-33 (1987). De Giorgis G, Miletto R, Iannuccelli M, Camuffo M, Scerni S
  15. Serotonergic drugs : effects on appetite expression and use for the treatment of obesity. Drugs. 67(1):27-55 (2007).Halford JC, Harrold JA, Boyland EJ, Lawton CL, Blundell JE
  16. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr. 1992 Nov;56(5):863-7 .Cangiano C, Ceci F, Cascino A, Del Ben M, Laviano A, Muscaritoli M, Antonucci F, Rossi- Fanelli F
  17. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett. 15;150(1):111-22 (2004). Das YT, Bagchi M, Bagchi D, Preuss HG.
  18. Data from “pharmaceutical substances” Kleeman 4th ed. 2000.
  19. Registry of Toxic Effects of Chemical Substances (RTECS)

 

5 HTP