How Appetite Suppressants Work

Appetite suppressants affect the appetite-regulating region of the brain called the hypothalamus; and work within the brain by blocking the re-uptake of the chemicals serotonin and norepinephrine to improve satiety.123456
Researchers and medical experts have worked for years to develop appetite suppressants – dietary supplements in the form of over-the-counter (OTC) and prescribed medications, which work by reducing your appetite for food, thereby helping you to lose weight. More specifically, the potential of treating obesity is enormous, bearing in mind that a volitional weight loss of 10 kg is associated with important risk factor improvement: blood pressure -10 mmHg; total cholesterol -10%; LDL cholesterol -15%; triglycerides -30%; fasting glucose -50%; and HDL cholesterol +8%.7
Appetite suppressants have a long history that dates back to the 1950s, when the German and Finnish militaries were reported to have issued amphetamines to soldiers for the enhancement of warfare during the Second World War.8 Following the war, amphetamines were redirected for use in the commercial marketplace, and sold as appetite suppressants until outlawed in most parts of the world by the late 1950s due to safety issues among which were addiction, tachycardia, and hypertension.9 Instantly appetite suppressing drugs became a rage among those who wanted to lose weight without effort, and such drugs were extensively prescribed by doctors all over the world. The industry then became flooded with OTCs, the most common of which was based on hoodia (which much later became a top selling product in its own right), a genus of 13 species in the flowering plant family apocynaceae, under the subfamily asclepiadoideae. Several appetite suppressants were based on a mix of natural ingredients, mostly using the natural diuretic green tea as the base, in combination with other plant extracts such as fucoxanthin found naturally in seaweed. Drugs of this class are frequently called stimulants and are members of the phenethylamine family, related to amphetamines for which the street name is ‘Speed’.

The market was later saturated with more appetite suppressants. Dexatrim is known generically as phenylpropanolamine a decongestant that works by constricting (shrinking) blood vessels (both veins and arteries) in your body. The constriction of blood vessels in your sinuses, nose, and chest allows drainage in these areas, which decreases congestion making it ideal for the treatment of allergies, hay fever, sinus irritation, and the common cold. However, phenylpropanolamine also causes a significant decrease in appetite, and is used in a variety of OTC diet products. Unfortunately, phenylpropanolamine has been associated with an increased risk of hemorrhagic stroke (bleeding into the brain or into tissue surrounding the brain), and although the risk is low the U.S. Food and Drug Administration (FDA) recommends that consumers not use any products that contain phenylpropanolamine.
Later renamed fat-burners due to the addition thermogenic ingredients, appetite suppressants like Ephedra, Apidex, and Fen-phen could be purchased without prescriptions. It was during the 1990s that the side-effects, sometimes mild and sometimes life-threatening started showing up. Many such drugs were either suspected or proven to damage heart valves and lead to heart attacks. In the year 2000, these drugs were withdrawn from the market owing to their harmful effects.

FDA-Approved Appetite Suppressants
Appetite suppressants affect the appetite-regulating region of the brain called the hypothalamus. They work by blocking the re-uptake of the chemicals serotonin and norepinephrine, which create that feeling of satiety received after eating a big meal. With more of these chemicals circulating in the brain, a feeling of fullness can occur. Appetite suppressants are the cornerstone of the pharmacological approach to treating obesity.

There are a number of anorexiant medications approved by the FDA for weight management. Anorexiants work by changing the way neurotransmitters behave in the brain. Neurotransmitters are chemicals stored in nerve cells that are released when a nerve is stimulated. A neurotransmitter is released from the axon (or end) of a nerve fiber and crosses a very tiny gap between nerve cells (known as the synapse) to stimulate the adjacent cell. Thus, neurotransmitters are chemicals used to create communication between nerve cells, or between nerve cells and other tissues, such as fatty tissue.
The most effective and most commonly prescribed anorexiant medication is Phentermine. It and all other anorexiants available work largely by activating an adrenalin-like neurotransmitter, known as norepinephrine (NE), both within the central nervous system and the sympathetic nervous system. There is some evidence that overweight individuals suffer from diminished baseline sympathetic nervous system activity or sympathetic “tone”. This has the ramification of relatively decreasing the basal metabolic rate of overweight and obese individuals. Consequently, by utilizing sympathomimetic amines one can effectuate an increase in the basal metabolic rate, which can be hugely important for weight loss purposes.
Besides phentermine, this class of medications includes two other notable appetite suppressants known as phendimetrazine and diethylpropion. By using a combination of long- and short-acting compounds, appetite suppression can be effectively experienced for extended lengths of time. An example of such a combination would be the use phentermine in the morning, followed by phendimetrazine or diethylpropion in the late afternoon.

Researched-Based Evidence on Anorexiant Medications
Numerous peer-reviewed clinical studies and journal articles have confirmed the appetite suppressing and weight loss properties of these medications, including the following.

An 866 eligible subject study, which at weeks 52 and 108 found that phentermin/topiramate (PHEN/TPM CR) was associated with significant, sustained weight loss along with improved cardiovascular and metabolic variables, and decreased rates of incident diabetes in comparison with placebo. PHEN/TPM CR was well tolerated over 108 weeks, with reduced rates of adverse events occurring between weeks 56 and 108, compared with rates between weeks 0 and 56.10
A meta-analytic study of 20 English-language weight-reduction studies, reported on the effect of > or = 6 months of pharmacologic therapy on weight loss and its maintenance to determine the clinical benefits of extended treatment, propose of treatment guidelines, and to identify future research needs. The pharmacologic agents included phentermine, mazindol, fenfluramine, dexfenfluramine, and fluoxetine. This study concluded that the benefits of extended treatment appear to outweigh the risks for those patients who are unable to lose sufficient weight without pharmacologic therapy, but who maintain adequate weight loss with long-term pharmacologic therapy.11
Diethylpropion is a selective serotonin 2C receptor agonist that works by decreasing food intake with few side effects. Its outcomes on weight are modest, but may be helpful in certain selected patients. The phentermine/topiramate combination has proved to be highly effective, achieving a 10% reduction in weight in the majority of patients.12
Past therapies for the treatment of obesity have typically involved pharmacological agents usually in combination with a calorie-controlled diet. Meta-analyses support a significant though modest loss in bodyweight with a mean weight difference of 4.7 kg (95% CI 4.1 to 5.3 kg) for rimonabant, 4.2 kg (95% CI 3.6 to 4.8 kg) for sibutramine and 2.9 kg (95% CI 2.5 to 3.2 kg) for orlistat compared to placebo at ≥12 months. Of the Phase III pharmacotherapies, lorcaserin, taranabant, topiramate, and bupropion with naltrexone all demonstrated significant weight loss compared to placebo at ≥12 months.12

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