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5-HTP is Nature’s Best Answer to Boosting Brain Serotonin Levels

By Dr. Michael Murray

In this article:


5-Hydroxytryptophan (5-HTP) is an amino acid that is the halfway step in the manufacture of tryptophan to the important brain chemical serotonin. As a dietary supplement, 5-HTP is derived most often from a natural source – a seed from an African plant (Griffonia simplicifolia). 

5-HTP is primarily used to boost levels of serotonin in the brain. It seems that low serotonin levels are a common consequence of modern living as the conversion of tryptophan to 5-HTP is reduced by a stress-filled lifestyle. Low brain serotonin levels make people feel anxious, more emotional, hungry, crave carbohydrates, and experience poor sleep quality. Obviously, these affect many people these days. Fortunately, clinical studies have shown that 5-HTP produces excellent results in dealing with situations associated with low serotonin levels. In fact, 5-HTP is the best natural approach based upon the results from these studies.1,2

Table 1 - The Effects of Different Levels of Serotonin

Optimal Level of Serotonin

Low Level of Serotonin

Hopeful, optimistic

Depressed

Calm

Anxious

“Good-natured”

Irritable

Patient 

Impatient

Reflective and thoughtful

Impulsive

Able to concentrate

Short attention span

Creative, focused

Blocked, scattered

Able to think things through

“Flies off the handle”

Responsive

Reactive

Does not overeat carbohydrates

Craves sweets and high carbohydrate foods

Sleeps well with good dream recall    

Insomnia and poor dream recall

‌‌‌‌How does Tryptophan Compare to 5-HTP?

In short, it really doesn’t, 5-HTP supplementation produces much better results compared to use of tryptophan. Tryptophan must be converted in the brain to 5-HTP first before it is then converted to serotonin. This conversion of tryptophan to 5-HTP is defined as the rate-limiting step in serotonin manufacture. So in short, if you are not converting tryptophan into 5-HTP, taking more tryptophan will not raise brain serotonin levels. 

The conversion of tryptophan to 5-HTP is impaired in many people due to high levels of stress-related hormones like cortisol, resistance to insulin and poor blood sugar control, or insufficient levels of key nutrients like B6 and magnesium. In addition, in order for tryptophan to enter the brain it must be transported via a carrier. This carrier also transports other amino acids to the brain, so it is not that efficient. 5-HTP easily crosses into the brain and does not require a carrier. While only 3% of an oral dose of L-tryptophan is converted to serotonin, in contrast more than 70% of an oral dosage of 5-HTP is converted to serotonin.3,4 5-HTP has an additional benefit in that it also increases feel-good serotonin levels, known as endorphins.

In the 1970s, the mood-elevating and calming effects of 5-HTP were compared to L-tryptophan.5,6  The results with 5-HTP were far superior. In fact, L-tryptophan was only slightly better than a placebo in most studies. In one study, 74 subjects matched in clinical features (e.g., age, sex) and mood scores were given either 5-HTP (200 mg/day), L-tryptophan (5 g/day), or a placebo.7 The subjects underwent a detailed mood evaluation using a standardized mood scale questionnaire at the beginning of the study and at the end of the 30-day trial. Results from this study showed that 17 out of 26 subjects given 5-HTP experienced a significant enhancement of mood compared to only 10 out of 25 given tryptophan and 4 out of 23 taking the placebo. 

Additional studies have shown 5-HTP to exert very favorable effects in improving mood scores compared to either a placebo or other mood-elevating compounds.7 5-HTP also exerts significant effects in promoting feelings of calm and focus.

‌‌‌‌How Does 5-HTP Improve Sleep Quality?

5-HTP has also shown better results than tryptophan in improving sleep quality. Serotonin has shown effects in promoting a better night’s sleep and also serves as the building block in the manufacture of melatonin. Several double-blind clinical trials have shown 5-HTP to produce good results in helping promote and maintain sleep, both in those that typically do not sleep well as well as in normal subjects. 

5-HTP supplementation has shown to help encourage REM (rapid eye movement) sleep. Dreaming is linked to REM sleep and is an important part of a healthy sleep cycle. 5-HTP increases REM sleep by about 25% while also increasing deeper levels of sleep (stages 3 and 4). It is able to increase the measures of quality sleep without increasing total sleep time by reducing less “deep” stages of sleep.10 In one study, the participants who took 200 mg of 5-HTP increased REM sleep by 15 minutes over the five nights of the study. That translates to an increase of dream time by about 3 minutes a night.

While 5-HTP does improve sleep quality even if it is taken during the day, it is important to mention that in the double-blind, placebo-controlled studies where 5-HTP supplementation was given during the day, it produced no greater reports of daytime drowsiness or fatigue than the placebo.8,9

‌‌‌‌How Effective is 5-HTP in Reducing Carbohydrate Cravings? 

5-HTP can be very helpful in reducing excessive carbohydrate consumption and supporting weight loss. More than fifty years ago, researchers conducted experiments in rats that were genetically inclined to develop obesity and showed that 5-HTP supplementation caused a significant reduction in food intake and prevented excessive weight gain. These rats were clinically obese as a result of a genetically determined low level of activity of the enzyme that converts tryptophan to 5-HTP, leading to low levels of serotonin in the brain. As a result, these rats craved carbohydrates and weren’t getting the message to stop eating until they consumed far greater amounts of food than normal rats. 

There is some evidence that many humans may be similarly predisposed to obesity due to genetic factors including this same mechanism of reduced formation of 5-HTP from tryptophan. Providing 5-HTP in a pre-formed manner could lead to higher brain serotonin levels, and further, reduced carbohydrate intake and appetite control.

Four human clinical trials showed that 5-HTP worked well as a weight loss aid in overweight women.11-14 These studies were conducted in Italy and showed that 5-HTP was able to reduce calorie intake and promote satiety despite the fact that these women were making no conscious effort to lose weight or reduce calorie intake. The studies showed that there were fewer calories from pasta and bread being consumed in the 5-HTP group. As a result, during the 5-6 weeks of these studies the average weight loss amounted to between 1 and 1.5 pounds per week. Think about how effective 5-HTP might be if a person aligned their diet and exercise program along with it.

‌‌‌‌What is the Best Way to Take 5-HTP?

5-HTP can cause stomach irritation and nausea, so for best results use enteric-coated capsules or tablets. These pills are prepared in a manner so that they will not dissolve in the stomach. Chewable tablets containing 5-HTP are another way to avoid nausea. When 5-HTP is being used for anything other than a nighttime sleep aid, the initial dosage is 50 mg three times per day. If the response is not sufficient after two weeks, the dosage can be increased to 100 mg three times per day. 

When 5-HTP is being used to promote a good night’s sleep, the usual dosage is 50 to 150 mg about a half hour before retiring. It is best to start with the 50 mg dosage for at least three days before increasing dosage. 5-HTP can be taken with food, but if taken for weight loss, take it 20 minutes before meals.

‌‌‌‌Are There any Contraindications for 5-HTP?

5-HTP is generally well-tolerated. There are a few situations where it should not be used:

  • Pregnancy or lactation
  • Parkinson’s disease unless a person is also taking the drug Sinemet® (carbidopa and levodopa).
  • Scleroderma (linked to a defect in tryptophan metabolism).
  • Patients taking the drugs methysergide and cyproheptadine.
  • If you are taking any other prescription medication, consult with your doctor or pharmacist regarding any possible interaction with 5-HTP.

‌‌‌‌Is 5-HTP Safe for Long-Term Use?

5-HTP can be used indefinitely as some people with a genetic defect in the conversion of tryptophan to 5-HTP require lifelong supplementation. Some experts recommend being monitored by regular (every year) eosinophil determination if 5-HTP is being used for long periods of time. This determination is part of a standard laboratory blood test known as a complete blood count (CBC) and helps screen for any unusual reaction to 5-HTP. 

References:

  1. Murray M.T., 5-HTP: The Natural Way to Overcome Depression, Obesity, and Insomnia. Bantam NY 1999.
  2. Turner E.H.; Loftis J.M.; Blackwell A.D..  Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan.  Pharmacol Ther  (2006) 109  325–338.
  3. In: (editors: Filippini G.A.; Costa C.V.L.; Bertazzo A.. )  Recent Advances In Tryptophan Research, Tryptophan and Serotonin Pathways.  Plenum Publ Corp: New York, NY.
  4. Magnussen I.E.; Nielsen-Kudsk F..  Bioavailability and related pharmacokinetics in man of orally administered L-5-hydroxytryptophan in steady state.  Acta Pharmacol Toxicol (Copenh)  (1980) 46  257–262.
  5. Byerley W.F.; Judd L.L.; Reimherr F.W.; et al. 5-Hydroxytryptophan. A review of its antidepressant efficacy and adverse effects.  J Clin Psychopharmacol  (1987) 7  127–137.
  6. Van Praag H.M..  Studies on the mechanism of action of serotonin precursors in depression.  Psychopharmacol Bull  (1984) 20  599–602.
  7. Jangid P.; Malik P.; Singh P.; Sharma M.; Gulia AK.. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr. (2013) 6(1) 29-34.
  8. Poldinger W.; Calanchini B.; Schwarz W..  A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine.  Psychopathology  (1991) 24  53–81.
  9. Wyatt R.J.; Zarcone J.; Engelman K..  Effects of 5-hydroxytryptophan on the sleep of normal human subjects.  Electroencephalogr Clin Neurophysiol  (1971) 30  505–509.
  10. Ceci F.; Cangiano C.; Cairella M.; et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects.  J Neural Transm  (1989) 76  109–117.
  11. Cangiano C.; Ceci F.; Cairella M.; et al. Effects of 5-hydroxytryptophan on eating behavior and adherence to dietary prescriptions in obese adult subjects.  Adv Exp Med Biol  (1991) 294  591–593.
  12. Cangiano C.; Ceci F.; Cascino A.; et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan.  Am J Clin Nutr  (1992) 56  863–867.
  13. Cangiano C.; Laviano A.; Del Ben M.; et al. Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients.  Int J Obes Relat 
  14. Das Y.T.; Bagchi M.; Bagchi D.; et al. Safety of 5-hydroxy-L-tryptophan.  Toxicol Lett  (2004) 150  111–122.

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