5-HTP

Tryptophan is an essential amino acid and influences serotonin levels

What is 5-hydroxytryptophan (5-HTP)

5-Hydroxytryptophan (5-HTP) is a metabolite of the amino acid L-tryptophan (LT), which is produced as an intermediate product during the conversion of L-tryptophan to serotonin. When 5-HTP is used, the conversion of L-tryptophan to 5-HTP is bypassed with the help of the enzyme tryptophan hydrolase - and thus the rate-limiting step in serotonin synthesis. Among other things, the human body uses 5-HTP to produce melatonin. Tryptophan hydrolase can be inhibited by numerous factors, including stress, insulin resistance, vitamin B6 deficiency and insufficient magnesium intake. At the same time, these same factors can increase the conversion of L-tryptophan to kynurenine by catalyzing tryptophan oxygenase, thus reducing the amount of L-tryptophan available for serotonin production. 5-HTP acts as an antioxidant, whereas L-tryptophan can actually increase oxidative damage. In commercial production, 5-HTP is obtained by extraction from the seeds of the African plant Griffonia simplicifolia.

How 5-HTP works

The effect of 5-HTP is mainly based on increasing serotonin levels in the central nervous system. It has been shown that after oral administration of 5-HTP, the concentrations of other neurotransmitters and centrally active substances such as melatonin, dopamine, noradrenaline and betaendorphin also increase.

Health benefits of 5-HTP supplementation

5-HTP can support weight loss by increasing the feeling of satiety 5-HTP can increase the feeling of satiety, which can cause you to eat less and lose weight. Weight loss can increase the production of hormones that make you hungry. These persistent feelings of hunger can make weight loss difficult to sustain in the long term (1, 2, 3). 5-HTP can counteract these hunger-inducing hormones by suppressing your appetite, helping you to lose weight (4). In one study, 20 subjects suffering from diabetes were randomly assigned to either a group that received 5-HTP or a group that received only a placebo. The results of this study showed that those who received 5-HTP consumed about 435 kcal less per day (5). In addition, 5-HTP primarily inhibited the absorption of calories in the form of carbohydrates, which was associated with better blood sugar control. Many other studies have found that 5-HTP increased satiety and supported weight loss in overweight and obese people (6, 7, 8, 9). In addition, animal studies have shown that 5-HTP may reduce excessive food intake due to stress or depression (10, 11).

• Summary: 5-HTP can increase satiety, which can help you eat less and lose weight.

5-HTP may help with depression by increasing serotonin levels

The effects of 5-HTP on symptoms of depression have been well studied. Although the exact cause of depression is not well understood, scientists believe that a serotonin imbalance can affect mood in a way that can lead to depression (12, 13). It is believed that 5-HTP supplements may alleviate symptoms of depression by increasing serotonin levels. Several small studies have concluded that 5-HTP can alleviate depression. However, two of these did not include a placebo group, which limits the validity of the results (14, 15, 16, 17, 18). Many of the studies conducted suggest that the potential antidepressant effects of 5-HTP are stronger in combination with other substances or pharmaceutical antidepressants than when these compounds are used alone (15, 19, 20, 21). In addition, many study reviews conclude that further, higher quality studies are needed before 5-HTP can be recommended for the treatment of depression (22, 23).

• Summary: 5-HTP supplements increase serotonin levels in the body, which can alleviate symptoms of depression. This is especially true when 5-HTP is combined with other antidepressant substances or medications.

5-HTP can alleviate the symptoms of fibromyalgia

Supplementation with 5-HTP could alleviate the symptoms of fibromyalgia - a disease characterized by pain in muscles and bones, as well as general weakness. There is as yet no known cause of fibromyalgia, but low serotonin levels have been linked to the condition (25).

The latter has led scientists to believe that increasing serotonin levels through 5-HTP supplements could help people suffering from fibromyalgia (26). In fact, some research suggests that 5-HTP can alleviate the symptoms of fibromyalgia, including muscle pain, sleep problems, anxiety and fatigue (26, 27, 28). In one study, subjects suffering from fibromyalgia who were given 5-HTP in combination with antidepressants known as monoamine oxidase inhibitors reported a significant reduction in pain (29). Overall, however, not enough research has been conducted to draw clear conclusions regarding the efficacy of 5-HTP for the treatment of fibromyalgia symptoms.

• Summary: 5-HTP may increase serotonin levels, which could help alleviate symptoms of fibromyalgia. However, further human studies are needed.

5-HTP may help reduce the frequency of recurrent migraine headaches It is believed that 5-HTP may help with migraines. Although the exact causes of migraine attacks are still under investigation, some scientists believe that migraine attacks may be triggered by low serotonin levels (30, 31). One study investigated the ability of 5-HTP and methylseid - a widely used migraine medication - to prevent migraine attacks (32). This study concluded that supplementation with 5-HTP over a 6-month period significantly reduced the number of migraine attacks in 71% of subjects (32). In another study with 48 test subjects, supplementation with 5-HTP resulted in a 70% reduction in the frequency of migraine attacks, while a reduction of only 11% was observed in the placebo group (33). Many other studies also suggest that 5-HTP could be an effective treatment option for migraine (28, 34, 35).

• Summary: 5-HTP may reduce the frequency of migraine attacks by increasing serotonin levels.

5-HTP may promote better sleep by increasing melatonin production

5-HTP stimulates the production of serotonin, which can be unconverted into the hormone melatonin. Melatonin plays an important role in regulating sleep. Levels of this hormone begin to rise in the evening, which promotes sleep, while they fall in the morning to make it easier to wake up. For this reason, supplementation with 5-HTP could promote sleep by increasing melatonin production.

A human study found that a combination of 5-HTP and gamma-aminobutyric acid (GABA) reduced the time it took to fall asleep, increased sleep duration and also improved sleep quality (36). GABA is a chemical messenger that promotes relaxation. A combination of 5-HTP and GABA is thought to have synergistic effects (36). In fact, several studies conducted on animals suggest that 5-HTP improves sleep quality and the effect is stronger when 5-HTP is combined with GABA (37, 38). However, while these results are promising, the lack of human studies makes it difficult to recommend 5-HTP for improving sleep quality, especially when used in isolation.

• Summary: 5-HTP may promote better sleep by increasing melatonin levels.

How the body absorbs 5-HTP

5-HTP is well absorbed after oral administration. Around 70 percent of the administered dose reaches the bloodstream. The presence of other amino acids does not hinder the absorption of 5-HTP. 5-HTP can therefore be taken with meals without impairing its effectiveness. In contrast to L-tryptophan, 5-HTP cannot take on any other metabolic physiological tasks, such as the formation of niacin or proteins. The serotonin level in the brain is strongly dependent on the 5-HTP and L-tryptophan levels in the central nervous system (CNS). 5-HTP can easily cross the blood-brain barrier without being dependent on the involvement of a transport molecule. L-tryptophan, on the other hand, can only enter the CNS with the help of a transport molecule. As this transport molecule is also utilized by several other amino acids, the presence of these competing amino acids can delay L-tryptophan transport into the brain.

Optimal dosage

The initial dosage for 5-HTP is usually 50 mg three times a day with meals. If the user does not respond sufficiently after two weeks, the dose can be increased to 100 mg three times a day. As some users react with slight nausea at the start of 5-HTP treatment, a gradual treatment with an initial dose of 50 mg and subsequent titration upwards is recommended.

With 5-HTP, the optimal dosage depends heavily on the desired effect and the area of application.

Here are some guidelines:

• Weight management: 250-300 mg per day, 30 minutes before a meal (5).
• Depression / mood improvement: 50-100 mg, three times a day with meals. A noticeable effect can be expected after one week at the earliest (18).
• Fibromyalgia: 100 mg, three to four times daily with meals. A noticeable effect can be expected after one week at the earliest (26).
• Migraine: 100-200 mg, two to three times a day with meals. A noticeable effect can be expected after one week at the earliest (32).
• Sleep support: 100-300 mg, 30 to 45 minutes before bedtime. A combination with GABA can improve the effect (36).

Safety and side effects

5-HTP is potentially safe and harmless when taken orally. However, there are concerns that 5-HTP may cause a serious side effect called eosinophilia. Some people believe that this side effect is caused only by contaminants in some 5-HTP products, but there is not enough scientific data to say whether this side effect is caused by 5-HTP itself, a contaminant or other factors. Until more is known, 5-HTP should be used with caution. Other potential side effects of 5-HTP include heartburn, stomach pain, nausea, vomiting, diarrhea, drowsiness, sexual problems, and muscle problems.

Precautions and warnings

• Pregnancy and lactation: 5-HTP may not be safe and safe to take orally during pregnancy and lactation.
• Down syndrome: There are reports that 5-HTP has caused seizures in some people suffering from Down syndrome. In a group of subjects suffering from Down syndrome, 15% of the study participants who received 5-HTP over an extended period of time experienced seizures.
• Operations: 5-HTP can affect a brain chemical called serotonin. Some medications administered during surgery can also affect serotonin levels. Taking 5-HTP before surgery could result in too high serotonin levels in the brain, which can result in serious side effects including heart problems, tremors and anxiety. For this reason, you should stop taking 5-HTP at least 2 weeks before an operation.

Interactions

5-HTP should not be combined with the following medications:

Medications for depression (antidepressants, MAO inhibitors).

5-HTP can increase the levels of a brain chemical called serotonin. Some medications for depression can also increase serotonin levels. Taking 5-HTP in combination with these anti-depressant medications could result in excessive serotonin levels in the brain, which can lead to serious side effects including heart problems, tremors and anxiety. For this reason, 5-HTP should not be used when taking medication for depression.

Care should be taken when combining 5-HTP with the following medications:

Dextromethorphan

5-HTP can increase the levels of a brain chemical called serotonin. Dextromethorphan can also increase serotonin levels. Taking 5-HTP in combination with dextromethorphan could result in too high serotonin levels in the brain, which can lead to serious side effects including heart problems, tremors and anxiety. For this reason, 5-HTP should not be used when taking dextromethorphan.

Meperidine

5-HTP can increase levels of a brain chemical called serotonin. Meperidine can also increase serotonin levels. Taking 5-HTP in combination with meperidine could result in excessive serotonin levels in the brain, which can lead to serious side effects including heart problems, tremors and anxiety. For this reason, 5-HTP should not be used when taking meperidine.

Pentazocine

5-HTP can increase levels of a brain chemical called serotonin. Pentazocine can also increase serotonin levels. Taking 5-HTP in combination with pentazocine could result in too high serotonin levels in the brain, which can lead to serious side effects including heart problems, tremors and anxiety. For this reason, 5-HTP should not be used when taking pentazocine.

References

1. https://www.ncbi.nlm.nih.gov/pubmed/29360396
2. https://www.ncbi.nlm.nih.gov/pubmed/20150577
3. https://www.ncbi.nlm.nih.gov/pubmed/19675105
4. https://www.ncbi.nlm.nih.gov/pubmed/16846858
5. https://www.ncbi.nlm.nih.gov/pubmed/9705024
6. https://www.ncbi.nlm.nih.gov/pubmed/2468734
7. https://www.ncbi.nlm.nih.gov/pubmed/1722953
8. https://www.ncbi.nlm.nih.gov/pubmed/1384305
9. https://www.ncbi.nlm.nih.gov/pubmed/22142813
10. https://www.ncbi.nlm.nih.gov/pubmed/14724051
11. https://www.ncbi.nlm.nih.gov/pubmed/8728550
12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471964/
13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3638388/
14. https://www.ncbi.nlm.nih.gov/pubmed/696719
15. https://www.ncbi.nlm.nih.gov/pubmed/28787372
16. https://www.ncbi.nlm.nih.gov/pubmed/4556909
17. https://www.ncbi.nlm.nih.gov/pubmed/4596091
18. https://www.ncbi.nlm.nih.gov/pubmed/11869656
19. https://www.ncbi.nlm.nih.gov/pubmed/4547418
20. https://www.ncbi.nlm.nih.gov/pubmed/1909444
21. https://www.ncbi.nlm.nih.gov/pubmed/23380314
22. https://www.ncbi.nlm.nih.gov/pubmed/27692695
23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415362/
24. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990568/
25. https://www.ncbi.nlm.nih.gov/pubmed/9802912
26. https://www.ncbi.nlm.nih.gov/pubmed/2193835
27. https://www.ncbi.nlm.nih.gov/pubmed/1521674
28. https://www.ncbi.nlm.nih.gov/pubmed/3913752
29. https://www.ncbi.nlm.nih.gov/pubmed/8906292
30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117050/
31. https://www.ncbi.nlm.nih.gov/pubmed/17970989
32. https://www.ncbi.nlm.nih.gov/pubmed/3536521
33. https://www.ncbi.nlm.nih.gov/pubmed/3308389
34. https://www.ncbi.nlm.nih.gov/pubmed/6397729
35. https://www.ncbi.nlm.nih.gov/pubmed/7034490
36. https://www.ncbi.nlm.nih.gov/pubmed/19417589
37. https://www.ncbi.nlm.nih.gov/pubmed/26921634
38. https://www.ncbi.nlm.nih.gov/pubmed/27150227

Further studies

1. Pharmacol Biochem Behav. 2003 Mar;74(4):877-82. selective augmentation of genioglossus electromyographic activity by L-5-hydroxytryptophan in the rat. Berry RB, Hayward LF.
2. Altern Med Rev. 2000 Feb;5(1):64-71. Use of neurotransmitter precursors for treatment of depression. Meyers S.
3. Biol Pharm Bull. 2003 Oct;26(10):1491-3. Effects of insulin and adrenalectomy on elevation of serum leptin levels induced by 5-hydroxytryptophan in mice. Yamada J, Sugimoto Y, Ujikawa M.
4. Eur J Pharmacol. 2000 Oct 6;406(1):159-62. serum leptin levels after central and systemic injection of a serotonin precursor, 5-hydroxytryptophan, in mice. Yamada J, Ujikawa M, Sugimoto Y.
5. Chin J Physiol. 1995;38(4):235-40. Serotonergic mechanisms involved in the suppression of feeding by 5-HTP in rats. Ju CY, Tsai CT.
6. Int J Obes Relat Metab Disord. 1998 Jul;22(7):648-54. effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients. Cangiano C, Laviano A, Del Ben M, Preziosa I, Angelico F, Cascino A, Rossi-Fanelli F.
7. Altern Med Rev. 1998 Aug;3(4):271-80. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Birdsall TC.
8. Adv Exp Med Biol. 1996;398:35-41. brain serotonin, carbohydrate-craving, obesity and depression. Wurtman RJ, Wurtman JJ.
9. Brain Res. 1991 Aug 2;555(2):245-50. Involvement of corticotrophin releasing factor (CRF) in the thermogenic and anorexic actions of serotonin (5-HT) and related compounds. Le Feuvre RA, Aisenthal L, Rothwell NJ.
10. Eur J Pharmacol. 1999 Oct 21;383(1):49-51. The serotonin precursor 5-hydroxytryptophan elevates serum leptin levels in mice. Yamada J, Sugimoto Y, Ujikawa M.
11. Int J Obes. 1987;11 Suppl 3:109-23. medial hypothalamic serotonin in the control of eating behavior. Leibowitz SF, Weiss GF, Shor-Posner G.