5-HTP can satisfy your appetite, lower BMI, and reduce hip circumference …

How to Hinder
Feelings of Hunger

Implicitly or explicitly, not having an opinion about
how we know when to stop eating is nearly inescapable
By Will Block

A well governed appetite is the greater part of liberty.
— Lucius Annaeus Seneca

F ood can play many roles in our lives. Delectable … scrumptious … lip-smacking … delicious food is one of the great pleasures of life. Food can also be a vehicle for self-medication (for example, for mood alteration). But excessive consumption of food can be a major problem, leading to overweight and obesity, which are forerunners of disease. What is at the root of appetite, hunger, and craving—you may have wondered? Exactly what is it that determines when you’ve had enough food? Implicitly or explicitly, not having an opinion about how we know when to stop is nearly inescapable.

Can’t Get No Satisfaction?

Without any clear idea of how we push ourselves away from the table, we might not be able to exercise some level of self-control. Horrifically, we might rapidly eat ourselves to death. The simple answer people usually give for how they stop is that they become satisfied. But is this a meaningful answer or merely a circular one?* More to the point, why does satisfaction come sooner for some and later for others … or why does it come sooner at some times, and later at other times? To the point, what can we learn and put into practice to master our appetites, especially when there is so much at stake regarding our health?

* Circular reasoning (CR) is a type of logical fallacy in which the proposition to be proved is assumed implicitly or explicitly in one of the premises. In other words, CR is a sentence or argument that restates rather than proves, and thus runs in a circle: Ingredient X is a great satisfier because it is fulfilling. The terms in the beginning of the sentence (great satisfier) and the end of the sentence (fulfilling) are interchangeable.

No One Has Cracked the Code

To help us to understand, and through that knowledge possibly change our behavior, a number of biochemical pointers have been identified. These include what are known as satiety hormones (anorexigenics) and hunger hormones (orexigenics). Among the former are leptin, obestatin, and cholecystokinin (CCK), and among the latter are ghrelin and orexin. There are many others in each category. But regrettably, there are many complex interactions among them that occur within the gastric and upper small intestines, and no one to date has cracked the code.

The Risk Factors of Overweight

When you carry around excess body weight, it’s not only a drag on your energy—not to mention the loss of esteem it engenders from negative self-image—the extra weight is also seriously detrimental to your health. Too much fat baggage spikes the most important risk factors for nearly all causes of morbidity and mortality. If you are overweight, and more so if you are obese, there is a substantial likelihood that you are on your way to one or more debilitating illnesses, such as type-2 diabetes, heart disease, cancer, and osteoarthritis, especially when it comes to weight-bearing joints. And altogether, these conditions lead to substantial economic burdens in your overall health care budget.

Too much fat baggage spikes the most
important risk factors for nearly all
causes of morbidity and mortality.

To date, conventional weight-management programs, in both the short- and long-term, are by and large unsatisfactory because there is no magic bullet (see “Durk Pearson & Sandy Shaw’s 21st Century Weight Loss Program” in the December, 2006 and the January 2007 issue). Rather, while adopting a low-glycemic diet, supplementing with a variety of dietary supplements, and orchestrating a physical exercise program can suffice, the discipline is often too great for many people.

Serotonin Helps Control Feeling of Appetite

It is fortunate that an important field of research deals with dietary supplements that contain molecules which act by controlling feelings of appetite. These appetite modulators include tryptophan, since it is a precursor of the neurotransmitter serotonin. Serotonin (5-hydroxy­tryptamine or 5-HT) is a monoamine neurotransmitter.* Derived from tryptophan, serotonin is a biochemical primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS) of animals, including humans. There is widespread acceptance that serotonin is a contributor to feelings of well-being and happiness.

* Monoamine neurotransmitters are either neurotransmitters or neuromodulators characterized by one amino group that is connected to an aromatic ring by a two-carbon chain (-CH2-CH2-). Every monoamine is derived from aromatic amino acids such as tryptophan, phenylalanine, tyrosine, and the thyroid hormones by the action of aromatic amino acid decarboxylase enzymes.

When tryptophan is consumed as part of your diet it is transported within the cells, where it is altered through enzymatic hydroxylation to form 5-hydroxytryptophan (5-HTP). Afterward, a decarboxylation process creates 5-HT (serotonin), which is synthesized within the serotoninergic neurons of the CSN, as well as within a type of endocrine cells of the GI system. Serotonin is thought to be a neuroinhibitor, exercising modulatory activity within the CNS, and with inhibitory effects on sexual behavior, sensitivity to pain, and appetite. In cases of serotonin deficiency (which can arise in different ways), there is a tendency to become depressed, to sleep poorly, and to overeat. It is believed that genetically-induced serotonin deficiency is a common factor in obesity, and there is no doubt that this compound has a major influence on eating behavior.1

The Take Away Lesson from Infamous Phen-Fen

The drug fenfluramine was one member of the now infamous phen-fen treatment for weight loss. Although very successful, fenfluramine was later associated with damage to the valves of the heart, pulmonary hypertension, and serotonergic receptor damage, and was withdrawn from the market. Because fenfluramine raised serotonin levels, it seems reasonable to believe that other substances that affect serotonin might also be useful for weight reduction.

Increased Serotonin Diminishes Appetite

Scientific papers about the effects of serotonin on appetite are not new to the literature. In fact, research goes back to the 1960s, and perhaps earlier. In a paper published in 1964,2 it was shown that increased levels of serotonin in rats—produced via intraperitoneal (body cavity) injections of the serotonin precursor 5-hydroxytryptophan (5-HTP) in small doses (from 1.9 mg/kg of body weight up to 15 mg/kg of body weight)—had the immediate results of reducing food consumption as the dose of 5-HTP increased. These doses are the equivalents of 26 mg to 207 mg of 5-HTP for a 187 lb human.

Genetically-induced serotonin
deficiency is a common factor in
obesity, and there is no doubt that
this compound has a major influence
on eating behavior.

Without Conscious Effort, 5-HTP Reduces Caloric Intake

In studies with humans, there have been several showing that use of 5-HTP can suppress appetite and cause weight loss. One such investigation, done at the University of Rome in 1989, examined 19 obese female subjects with a body mass index (BMI) ranging between 30 and 40, who were given either 5-HTP at 8 mg/kg/day or placebo in a double-blind crossover study.3 An amazing 79% of the women reported a decrease in appetite while taking 5-HTP. This was borne out by measurements of their actual caloric intake. And this reduced caloric intake occurred despite the fact that the 19 participants made no conscious effort to eat less. Also, placebo participants consumed about 2,300 calories per day, while those taking 5-HTP ate 508 calories less (1,800 calories daily), a 22% reduction compared to placebo. 5-HTP use led to a significantly enhanced sense of satiety after eating over, the course of 5 weeks. Furthermore, women taking 5-HTP effortlessly lost more than 3 lbs, an average of 3.1 lb with 5-HTP, vs. 0.9 lb with placebo. The amount of 5-HTP used daily (taken in three divided servings) was 3.6 mg per pound of body weight; this corresponds to a total of 450 mg per day for a 125-lb woman, or 900 mg per day for a 250-lb woman.

5-HTP Produces Weight Loss, Diet or Not

In a second study, the same Italian researchers put 14 obese women on a 1200-calorie/day diet for 6 weeks.4 Some were given 300 mg of 5-HTP 30 minutes before meals (a total of 900 mg per day), while the others were given placebo. Over the 6-week period, the women taking 5-HTP lost 6.8 lb, on average, compared with 1.5 lb for the women on placebo.

Reduced caloric intake occurred
despite the fact that
the 19 participants made
no conscious effort to eat less.

In the same study, the researchers had previously tested the same women during a 6-week period in which they were given the same daily 5-HTP (or placebo) regimen, but without any dietary restrictions. Over that 6-week period, the average weight loss was less (not surprisingly), but still appreciable: 3.5 lb with 5-HTP and 1.1 lb with placebo. Thus, with or without dietary restrictions, the women in this study lost substantial amounts of weight (10.3 lb total) while taking 5-HTP—4 times as much as with placebo (2.6 lb total).

5-Fold Greater Weight Loss with 5-HTP

In yet a third study, of essentially the same design as the one just discussed, but with 20 obese women, the same Italian researchers found that 300 mg of 5-HTP taken 30 minutes before meals resulted in a 6-week weight loss of 7.3 lb with 5-HTP vs. 1.8 lb with placebo when the women were on the restrictive 1200-calorie/day diet.5 Without the diet, the women had 6-week weight losses of 3.7 lb and 0.6 lb, respectively. Thus, the total weight losses over the 12-week period of this study were 11 lb with 5-HTP and 2.4 lb with placebo—a nearly 5-fold difference. The 11-lb weight loss represented 5% of the women’s starting weight of 220 lb.

In this third study, 5-HTP also produced dramatic results in terms of the women’s feelings of early satiety, i.e., feeling full earlier than usual during a meal. When the women were not on the restrictive diet, 100% of those who were taking 5-HTP reported early satiety. Even when they were on the diet, however (but taking 5-HTP), this feeling persisted: the figure then was a remarkable 90%. Clearly, the feeling of early satiety led the women to eat less than usual, resulting in the weight losses observed.

Slow Buildup Is Best with 5-HTP

In the studies discussed above, about two-thirds of the women reported mild nausea while taking these very large doses (up to 900 mg/day) of 5-HTP; in the second and third studies, nausea occurred during the first 6 weeks but not during the second 6 weeks. In real life, the easy way to avoid nausea caused by 5-HTP is to start with a small amount and build it up gradually over a period of 2 weeks; this is sufficient time to allow the body to adjust, demonstrating that the supplement is well tolerated.

Benefits from Lower Levels of 5-HTP

From the above studies, it isn’t clear whether lower amounts of 5-HTP might not have similar, or even equivalent benefits to those described above. There is no indication in the literature that this has been tested before. Now, in a new randomized, double-blind, placebo-controlled trial, 20 healthy, overweight females were randomly assigned to either 5-HTP (10 subjects) or a placebo (10 matched subjects) over the course of 4 weeks.6 At the same time, each of the subjects was also given a personalized reduced-caloric diet to follow. The amounts of 5-HTP or placebo used were 10.24 mg 5 times daily (total 51.2 mg daily), involving fasting in the morning, at mid-morning, before lunch, in the afternoon, and before dinner, or an identical placebo for 4 weeks. The active ingredients were delivered via oral cavity spray. Their effectiveness was evaluated by the assessment of 24-hour urinary 5-hydroxyindoleacetic acid levels (5-HIAA). The urinary excretion of 5-HIAA, the main metabolite of serotonin, reflects the content and turnover of GI serotonin. The amount of serotonin reaching the CNS is affected by the extent to which 5-HTP is transformed to serotonin in the periphery and 5-HIAA is the best reflection of that conversion.

Secondary endpoints were the assessment of sensation of appetite, body composition, and severity of binge eating. It was found that the supplemented group had a significant increase of 24-h urinary 5-HIAA levels, and a decrease in appetite while the placebo group did not show significant changes. There were significant changes in body composition, as measured by the mean change in BMI, skinfold thicknesses, arm circumference, and hip circumference.

The study found that 5-HTP administered via spray to the oral cavity is adequately absorbed, as confirmed by the increases in 24-h urinary 5-HIAA. Also found was that supplementation with 5-HTP increases the feeling of satiety associated with a decrease in BMI.

This is the first study in humans, to our knowledge, that demonstrates the effectiveness of 5-HTP sprayed in small quantities directly into the oral cavity for reducing BMI. The existing literature, reviewed above, has only found efficacy in controlling appetite with the use of oral solid supplements between 500–900 mg per day of 5-HTP. In a previous study, the same researchers demonstrated that a lower quantity of 5-HTP (39 mg daily), administrated as a sublingual spray 5 times a day, is effective in reducing the hunger feeling.7

When the women were not on
the restrictive diet, 100% of those
who were taking 5-HTP
reported early satiety.

Combination Pharmacotherapy?

To be fair, the researchers thought that the effect on BMI could be linked to the presence of other active components in the dietary supplement. These included Centella asiatica L. (11.7mg), Taraxacum officinale (11.7mg), Cynara scolymus (9.75mg), Paullina sorbilis L. Mart (4.55mg), and Alga klamath (39 mg). However, there is no credible scientific information indication any satiety, weight loss, or BMI decreases in any amounts for these ingredients. Furthermore, the suggestion that “combination pharmacotherapy,” can produce results not found for any component in any amount seems unlikely. However, of the other ingredients, Guaranà (P. sorbilis) is known for its stimulatory effect on fat metabolism; Gotu kola (C. asiatica) is useful for its beneficial effects on blood and lymph circulation; Dandelion (T. officinale) has an anti-oxidative and diuretic effect; artichoke (C. scolymus) has a detoxifying action; and klamath algae (A. klamath) has a high content of nutritive substances including phenylethylamine, which has been shown to improve mood, albeit at much higher ingested levels.

When Less Oral Solid 5-HTP May Yield Similar Sublingual Benefits

5-HTP drink mix as a first course?
Regarding the mood status (not enough 5-HTP?) and the severity of binge eating, there were no significant differences identified between groups. Again, it is important to stress that the observed safety of the supplements was consistent with the known effects of 5-HTP supplementation from previous studies. Finally, the present study indicates that 5-HTP given via spray to the oral cavity is adequately absorbed, as confirmed by the increase in 24-h urinary 5-HIAA. And to repeat, supplementation of overweight women with sprayed 5-HTP increased feelings of satiety associated with a decrease in BMI. It may be that smaller amounts of solid oral 5-HTP, say 37.5 mg at a time, taken 5 times daily—and especially when properly cofactored with vitamins, other amino acids, minerals, and other nutrients chosen from detailed studies of the body’s metabolic pathway maps—will produce the equivalent effects of 10.24 mg taken in 5 oral spray administrations, which may very well succeed for the desired payoffs: satiety, lower BMI, and reduce waist circumference. It seems to be a good bet.


  1. Wurtman RJ, Wurtman JJ. Brain serotonin, carbohydrate-craving, obesity and depression. Adv Exp Med Biol 1996;398:35-41.
  2. Joyce D, Mrosovsky N. Eating, drinking and activity in rats following 5-hydroxytryptophan (5-HTP) administration. Psychopharmacologia 1964 Jun 8;5:417-23.
  3. 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.
  4. Cangiano C, Ceci F, Cairella M, Cascino A, Del Ben M, Laviano A, Muscaritoli M, Rossi-Fanelli F. Effects of 5-hydroxytryptophan on eating behavior and adherence to dietary prescriptions in obese adult subjects. Adv Exp Med Biol 1991;294:591-3.
  5. Cangiano C, Ceci F, Cascino A, Del Ben M, Laviano A, Muscaritoli M, Antonucci F, Rossi-Fanelli F. 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.
  6. Rondanelli M, Opizzi A, Faliva M, Bucci M, Perna S. Relationship between the absorption of 5-hydroxytryptophan from an integrated diet, by means of Griffonia simplicifolia extract, and the effect on satiety in overweight females after oral spray administration. Eat Weight Disord 2011 Dec 5. [Epub ahead of print]
  7. Rondanelli M, Klersy C, Iadarola P, Monteferrario F, Opizzi A. Satiety and amino-acid profile in overweight women after a new treatment using a natural plant extract sublingual spray formulation. Int J Obes (Lond) 2009 Oct;33(10):1174-82.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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