5 HTP and Weight Loss

What is 5 HT?

5 HT is also known as 5-hydroxytryptamine or more commonly as serotonin. It is a monoamine neurotransmitter synthesized from the amino acid, tryptophan.

L-tryptophan is converted to 5-hydroxy-L-tryptophan or 5 HTP. 5 HTP is the precursor of serotonin. Therefore, all the effects of 5 HTP in weight loss are due to serotonin or 5 HT.

The two major sites of serotonin secretion in the body are the central nervous system and the enterochromaffin cells of the gastrointestinal system. The enterochromaffin cells are responsible for 90% of the serotonin produced in the body. A very small amount of 5 HT is also produced in bone cells.

5 HT is stored and transported in platelets. When platelets encounter blood clots, they release their store of serotonin and the monoamine compound serves as a vasoconstrictor while also promoting healing.

5 HT also controls the release of growth factors such as insulin-like growth factor and hormones such as insulin. It can also directly act as a growth factor.

Serotonin receptors abound in the central nervous system as well as the cardiovascular and musculoskeletal systems.

These receptors not only control serotonergic activities, but they also control the release of other neurotransmitters such as glutamate, GABA, dopamine, acetylcholine, epinephrine, and norepinephrine as well as hormones such as prolactin, oxytocin, cortisol, vasopressin, and substance P.

Therefore, 5 HT exerts its effects on several organ systems in the body. In the brain, it can produce excitatory and inhibitory responses depending on the serotonin receptors mediating the response. Because of these effects, 5 HT can cause profound effects and its levels should be closely monitored.

When 5 HT levels rise above normal values, a state of serotonin toxicity called serotonin syndrome results.

Alternatively, when 5 HT levels are low, clinical symptoms of depression, social withdrawal, lethargy, and weight gain results.

Generally, carbohydrates increase 5 HT levels in the blood and brain while proteins decrease the amount of serotonin produced.

This is ironic because the precursor of serotonin is tryptophan, an amino acid.

However, proteins flood the body with other amino acids that compete with tryptophan to cross into the brain. Carbohydrates, on the other hand, drive amino acids to be absorbed into different cells of the body and leave tryptophan behind. This increases the amount of tryptophan that can cross into the brain to be used in the synthesis of 5 HT.

Furthermore, proteins rich in tryptophan are great for the production of 5 HT. Such protein sources include meat, poultry, dairy products, and nuts.

Also, foods containing higher amounts of tryptophan than similar branched amino acids such as leucine, which may compete for absorption and transport across the blood-brain barrier, encourage 5 HT syntheses.

Such foods with high tryptophan to leucine ratios include banana and papaya. Whole wheat and rye bread have low tryptophan-leucine ratios and can, therefore, inhibit 5 HT production.

How 5 HT and 5 HTP Control Appetite

Recent studies are providing new insights into how 5 HT reduces appetite. The process starts while eating and continues thereafter.

At first, the smell of food triggers the release of dopamine in the brain. Dopamine then increases appetite.

However, serotonin levels are then increased gradually while eating. This serotonin then binds to 5 HT2C receptors found on the brain cells that produce dopamine. This action stops further release of dopamine and suppresses appetite.

However, 5 HT2C is not the only serotonin receptor involved in suppressing appetite, 5 HT1B is also involved.

Also, serotonin receptors found in the hypothalamus inhibits a compound called neuropeptide Y. Neuropeptide Y stimulates hunger and food cravings.

Lastly, 5 HT also activates a different set of receptors called MC4Rs (melanocortin-4 receptors).

Serotonin drugs that bind to 5 HT1B and 5 HT2C receptors are especially useful in the treatment of obesity because they reduce appetite. Such drugs include D-fenfluramine, fluoxetine, sibutramine, other SSRIs (selective serotonin receptor inhibitors), and 5 HT2C receptor agonists.

5 HT, Appetite and Weight Loss

When 5 HT reduces the appetite, it inhibits the incessant carbohydrate cravings that fuel obesity.

Either through serotonin receptors like 5 HT1B and 5 HT2C or other receptors such as MC4Rs, 5 HT has been used successfully to achieve weight loss.

Although some drugs that can reduce appetite and promote weight loss have been withdrawn from the market, experts believe that a better understanding of serotonin and melanocortin systems and how they are intertwined can help produce better drugs for weight loss.

Most of the current 5 HT drugs do not provide very specific actions. Because they bind to other 5 HT receptors besides 5 HT1B and 5 HT2C, these drugs can trigger very serious side effects that make them too risky to use for achieving weight loss.

Clinical Studies of 5 HT, 5HT Drugs, Appetite, and Weight Loss

Some studies have been done on the relationship between appetite, obesity, and the drugs that increase the levels of 5 HT. One of these is a 2005 study published in the journal, Current Drug Therapies.

The study identified that 5 HT drugs can reduce appetite before and during eating.

However, because these drugs target multiple serotonin receptors in different parts of the body, they do produce rather serious side effects.

The new drugs currently being tried for treating obesity and promoting weight loss are known to target 5 HT2C receptors only in the central nervous system.

Another study published in the journal, Neuropsychopharmacology, in 2002 even went deeper by studying how different variants of 5 HT2C receptors affect weight loss.

The study involved 57 healthy girls who were experiencing weight loss and 91 healthy girls who had normal weights. The researchers looked for subtypes of 5 HT2C receptors.

It is known that the gene responsible for coding for 5 HT2C receptors exhibit polymorphism. In this case, in some of the proteins making up the proteins of 5 HT2C receptors, the amino acids, serine, and cysteine are normally substituted for each other.

This study found out that there were more girls with the serine-substituted subtype of 5 HT2C receptors in the weight loss group than in the normal-weight group.

This means that 5 HT2C is indeed involved in appetite control and weight loss and also that some people will respond to serotonin better than others and achieve more pronounced weight loss over the same period of time.

A 1999 study published in the journal, Obesity Research, described the dose-response of sibutramine in achieving weight loss.

Sibutramine is an SNRI (serotonin and norepinephrine receptor inhibitor). This means that it blocks the clearance of the neurotransmitters, serotonin, and norepinephrine from nerve endings allowing both of them to act longer.

The study was completed by 683 obese patients who were randomly assigned different doses (1, 5, 10, 15, 20, or 30 mg per day) of sibutramine or placebo over 24 weeks.

The result not only shows that weight loss was dependent on the dose of sibutramine taken but also that after 4 weeks, each dose of sibutramine showed the same difference in producing weight loss as early as the 4^th week of the study.

Also, the weight loss produced came with other benefits such as:

• Increased serum levels of high-density lipoprotein cholesterol
• Reduced serum levels of triglycerides low-density lipoprotein, total cholesterol, and uric acid

The most common adverse effects of this drug were dry mouth, insomnia, and anorexia although there were also slight increases in pulse rate and blood pressure in some patients.

5 HTP, 5 HT Drugs, and Weight Loss

Sibutramine is one of the few FDA-approved drugs for treating obesity and achieving weight loss.

Besides its ability to produce clinically significant weight loss, sibutramine also reduces abdominal fat and reduces metabolic syndromes caused by high levels of lipids, blood glucose, uric acid, and insulin.

Recently, a new drug known as Belviq was approved by the FDA for treating obesity in people with high cholesterol levels, high blood pressure, or type 2 diabetes. It is the first weight-loss drug to be approved by the FDA in 13 years.

Belviq contains lorcaserin and it suppresses appetite by binding to 5 HT2C receptors in the brain.

However, while it is better than the placebo in trials, Belviq did not produce any dramatic effects. In 3 trials pooling over 8,000 obese patients who took the drug for a year or longer, Belviq produced an average of 3 – 3.7% reduction in weight.

However, the recommendation given is that Belviq should be stopped in patients who do not experience at least 5% in weight reduction after 12 weeks of using the drug. For such patients, taking Belviq for longer is not likely to produce better results.

Belviq does have its side effects including serotonin syndrome when it is used along with some other 5 HT drugs. It may also cause headache, fatigue, dizziness, dry mouth, constipation, nausea, low blood sugar, and cough.

Belviq is recommended to be used along with lifestyle changes such as exercise and a low-calorie diet.

However, 5HT drugs produce some serious side effects, especially on the heart. Most of such drugs that were previously approved for weight loss have been withdrawn from the market because of these side effects. Therefore, the FDA is wary of approving new ones without comprehensive clinical trials.

Even lorcaserin which is the active ingredient of Belviq was previously rejected in 2010 because of concerns of high risks of cancer in animal studies (more studies have shown that such risks are very low in humans).

Still, most people prefer alternatives to conventional 5 HT drugs for achieving weight loss.

Instead, there are natural proprietary 5 HTP formulas such as the one used in Serotonin Plus Weight Loss Plan or even herbal preparations that help improve serotonin production in the body.

Basically, the aim is to increase the level of serotonin in the brain. This can be achieved by taking natural 5 HTP preparations (5 HT is the precursor to serotonin) which are safer than 5 HT drugs; it can also be done by taking tryptophan and vitamin B6 supplements since tryptophan is the amino acid used to synthesize serotonin in the brain and vitamin B6 is a cofactor needed to drive serotonin synthesis.

Also, diet plays an important role in serotonin synthesis.

Low serotonin levels increase appetite especially cravings for carbohydrates and carbohydrates do improve serotonin synthesis because they reduce the number of other amino acids competing with tryptophan for entry into the brain.

Therefore, low-caloric carbohydrates and low-fat foods are recommended for combining with 5 HT medications. By taking carbohydrates with low calories, weight gain can be prevented while increasing serotonin synthesis in the brain.