pharmacological treatment of obesity

Anorexics, anorexigenics or appetite suppressants are substances (dietary supplements or drugs) that reduce the appetite and cause a person to eat less

Criteria of an ideal appetite suppressant:

1- Should be safe and acceptable for long term administration.

2- Should produce a dose related reduction in the body fat.

3- Should spare body proteins and other body tissues.

4- Should be free from significant side effects and abuse potential.

Categories of drugs used to treat obesity:

A) Adrenergic agonists:

Amphetamine and related drugs such as methamphetamine are a group of drugs that act by increasing levels of norepinephrine, serotonin, and dopamine in the brain (indirectly acting sympathomimetics acting centrally).

Amphetamines are not recommended as they are addictive and have many side effects like Dry mouth and Difficulty in sleeping.

Other adrenergic agonists like phenylpropanolamine (PPA) which is a noncatecholamine sympathomimetic weight-loss agent. It acts indirectly by stimulating release of noradrenaline and stimulation of α and β receptors, It acts peripherally. but there is an association between phenylpropanolamine and hemorrhagic stroke and that phenylpropanolamine not to be considered safe for over-the-counter use.

A number of drugs have been developed and marketed to replace amphetamines as appetite suppressants. These anorectic drugs include phendimetrazine and phentermine (lonamin®, Fastin®, Adipex®). They produce some amphetamine-like effects. Of these diet pills, phentermine is the most widely prescribed and most frequently encountered on the illicit market. Fenfluramine and dexfenfluramine are used in combination with phentermine (fenphen). They were removed from the U.S. market due to heart valve problems.

Fenphen: An anti-obesity medication (an anorectic) which consisted of two drugs: fenfluramine and phentermine. After reports of valvular heart disease and pulmonary hypertension, primarily in women who had been undergoing treatment with Fen-phen, the Food and Drug Administration (FDA) requested its withdrawal from the market in September 1997. It shows also problems due to euphorigenic effects.

B) Serotonergic agents:

Stimulate release of serotonin and prevent its reuptake. Fenfluramine and dexfenfluramine increase the level of the neurotransmitter serotonin, a chemical that regulates mood, appetite and other functions. but They were removed from the U.S. market due to heart valve problems.

Other serotonergic agents:

Sibutramine (Meridia®, Sibotrim®, Slimax® and Dietmax®):

It works by inhibiting the reuptake of serotonin and norepinephrine (it also inhibits dopamine reuptake but to a lesser extent). Consequently causing a feeling of satiety and leading to an increase in thermogenesis. It differs from the mechanism of action of fenfluramine and dexfenfluramine in that it does not induce the release of serotonin (This induction is believed to have led to fenfluramine's risk for valvular heart disease).

Serotonin activates some neurons and melanocortin-4 receptors, or MC4Rs, to curb appetite and at the same time blocks other neurons that normally act to increase appetite.

Sibutramine hydrochloride is given by mouth in an initial daily dose of 10 mg, usually taken in the morning. Patients who cannot tolerate 10 mg daily may benefit from a dose of 5 mg daily. Treatment with sibutramine should be re-evaluated if weight loss is less than 2 kg in the first 4 weeks of therapy. At this stage, the dose may be increased to a maximum of 15 mg daily, taking into consideration effects on heart rate and blood pressure, or treatment may need to be stopped. Treatment should not be given for longer than 1 year.

Side effects: Allergic reactions (difficulty in breathing, swelling of lips, tongue, or face or hives), irregular heartbeat, high blood pressure (severe headache, blurred vision) or seizures.

Other, less serious side effects include: restlessness, tremors, nervousness, mild headache, insomnia, dry mouth or constipation.

Contra-indications:

Sibutramine should be avoided in patients with a history of eating disorders such as anorexia nervosa and bulimia nervosa.

It is also contra-indicated in patients with uncontrolled or poorly controlled hypertension and should be used with caution in patients with a history of, or with, well-controlled hypertension. Blood pressure and heart rate should be monitored.

Sibutramine should not be used in patients with a history of cerebrovascular disease or cardiovascular disorders such as cardiac arrhythmias, heart failure, peripheral arterial occlusive disease and coronary artery disease. It should be avoided in patients with severe hepatic or renal impairment; caution has been advised when using sibutramine in those with mild to moderate renal impairment as the impairment in serotonin metabolism is closely correlated with the decrease in renal function. Accumulation of serotonin in the circulation occurs increasing its side effects.

Sibutramine should also not be used in patients with bipolar disorder, Tourette's syndrome (inherited neuropsychiatric disorder with onset in childhood, characterized by the presence of multiple physical tics and at least one vocal tic (, hyperthyroidism, phaeochromocytoma, benign prostatic hyperplasia (Serotonin produced a reversible and dose-dependent contraction of the detrusor muscle), or a history of drug or alcohol abuse. It should be used with caution, if at all, in patients with glaucoma. Sibutramine should also be used with caution in patients with a history of depression, seizures or gallstones (which may be precipitated or exacerbated by weight loss), or a family history of motor or verbal tics.

Any centrally-acting drug such as sibutramine may impair the ability to perform tasks requiring judgement or motor or cognitive skills; if affected, patients should not drive or operate machinery.

Sibutramine is in the FDA pregnancy category C. Also it is not known whether Meridia passes into breast milk. It is recommended not to use sibutramine unless after consulting a doctor. The safety and effectiveness of sibutramine have not been studied in children younger than 16 years of age.

Interactions:

Sibutramine should not be given with, or within at least 2 weeks of stopping an MAOI such as isocarboxazid, tranylcypromine or phenelzine. At least 2 weeks should elapse between discontinuation of sibutramine and starting therapy with an MAOI.

There is a risk of the serotonin syndrome (accumulation of vasoconstrictor catecholamines and risk of hypertensive crisis and cerebral hemorrhage) developing if sibutramine is used with other serotonergic drugs such as:

· SNRIs: venlafaxine, amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), imipramine (Tofranil)

· SSRIs: fluoxetine (Prozac), paroxetine (Paxil), or fluvoxamine (Luvox)

· Sumatriptan, lithium, pethidine, fentanyl, dextromethorphan and pentazocine.

Caution is advised when sibutramine is given with other drugs that may increase heart rate or blood pressure such as ephedrine, phenylpropanolamine, and pseudoephedrine. It should not be used with other centrally acting anorectics. Alcohol should be avoided.

Inhibitors of the cytochrome P450 isoenzyme CYP3A4, such as ketoconazole and erythromycin, may increase plasma concentrations of sibutramine. Conversely, inducers of this isoenzyme, such as rifampicin, phenytoin, carbamazepine and phenobarbital, may reduce plasma concentrations of sibutramine.

C) Drugs affecting fat absorption:

Orlistat (XENICAL®)

XENICAL Unlike other weight-loss drugs that act in the brain or central nervous system to suppress appetite or to speed up metabolism but ,works in the digestive system to block about one-third of the fat in the food you eat from being digested.

Mechanism of action : XENICAL is a pancreatic lipase inhibitor, attaches to the lipases and blocks them from breaking down some of the fat you have eaten, the undigested fats cannot be absorbed and is eliminated in your bowel movement.

Dose : The recommended dose is one capsule 120-mg by mouth at each main meal or up to 1 hour after a meal that contains fats (up to three times a day).

Meal should contain no more than about 30% of calories from fat and if you occasionally miss a meal or have a meal without fat, you can omit your dose of XENICAL.

Side Effects : As XENICAL blocks the absorption of dietary fat, some changes in bowel habits will occur.

These changes include gas with oily discharge, an increased number of bowel movements and an inability to control them, particularly after meals containing higher amounts of fat than are recommended.

Contraindications: XENICAL shouldn't be taken during pregnancy, nursing, diabetes (reduce blood glucose level) or with food absorption problems.

XENICAL reduces the absorption of any fat soluble substances such as fat soluble vitamins, so daily multivitamin is recommended with spacing of doses.

Acarbose (GLUCOBAY®)

Mechanism of action: A competitive inhibitor of intestinal alpha-glucosidases and pancreatic alpha-amylase which delay the absorption of complex carbohydrates so reduces the abnormally high blood sugar levels that occur after each meal hence it has been prescribed for treatment of diabetes.

Furthermore, the reduced rate of digestion leaves one feeling full for long time in this way, acarbose can aid weight loss by acting as a powerful appetite suppressant but need concomitant diet control and exercise.

Dosage: For appetite suppression, take one 50mg tablet up to three times daily.

The tablets should be chewed and swallowed prior to a meal or with the first mouthful of food.

Taking acarbose even about 15 minutes before the meal considerably reduces its efficacy.

Studies of several years show that, the effect of acarbose remained constant over the entire period of treatment meaning, the enzymes in the small intestine lose none of their activity and their susceptibility to inhibition by acarbose is maintained.

Side effects: Bloated feeling, diarrhea, stomach pain or discomfort.

In combination with other diabetic medications, (Glyburide, Glipizide, Metformin or insulin), acarbose may cause hypoglycemia (low blood glucose).

Caution: kidney disease, liver disease, stomach or bowel disease, unusual or allergic reaction to acarbose, pregnant or trying to get pregnant and breast-feeding.

Some drugs should not be taken at the same time with acarbose, include thiazides and diuretics, oral contraceptives, thyroid treatments, estrogens, phenytoin, sympathomimetics, calcium channel blockers and isoniazid.

Glucobay® dose not produce significant loss in body weight when used alone and not approved by FDA for obesity but for management of blood glucose level in diabetes.

Chitosan (chitocal®)

Chitosan is a polysaccharide obtained from exoskeleton of crustaceans e.g. shrimps.

Chitocal® also contains Gymnema Sylvestre; an Indian herb called Gurmar that means the sugar destroyer which prevent the absorption of 50% of dietary sugars.

It can excrete 72% of dietary fat with proper dose. The average weight loss is about 3-7kg monthly with regular use of Chitocal.

Mechanism of action:

1) Chitosan is dissolved in the stomach forming a gel which traps any fats and decrease its absorption and storage

2) Reduce LDL and triglycerides level

3) It greatly inhibits the absorption of carbohydrates

Advantages:

• Reduce body fats especially abdominal, buttocks & thigh fats.
• No drug-drug interactions.
• Safe for cardiac, renal, hepatic and hypertensive patients.
• No special diets are needed. Eat what you want from any kind of food you like, just reduce the quantities.
• The excellent choice for long term obesity control.
• Great safety, locally acting on alimentary foods, no CNS, hormonal or enzymatic effects.

Dose: 1 capsule 1/4 hr before light meals.

2-3 capsules 1/4 hr before main meal.

For maintenance of desired weight; 1-2 capsule 1/4 hr before the main meal.

Side effects: It decreases the bioavailability of essential fatty acids and fat soluble vitamins when administered concomitantly.

D) Others:

1- Chromium picolinate Chromate^®, Chromax^®, Hi chrome^®, Diet booster^®:

-Chromium picolinate is a nutritional supplement that works to increase the efficiency of insulin to optimal levels. The most common usage for chromium picolinate is as a weight loss aid; claims that this supplement can melt fat, drastically reduce appetite and increase metabolism account for the popularity of chromium picolinate in our diet-obsessed culture.

- Chromium is a naturally-occurring mineral, trace amounts of which are found in everyday foods like meat, poultry, fish, and whole-grain breads.

- Picolinic acid is a metabolite of tryptophan. It forms a stable absorbable complex with chromium so aids in efficient chromium absorption and increases its bioavailability.

Relation between chromium picolinate and insulin:

- Chromium is used to treat diabetic patients as it is considered an integral part of "glucose tolerance factor" (GTF). Each GTF molecule, a hormone like compound, requires chromium as its central atom. GTF works with insulin to transport glucose from the blood into the cells.

- Chromium picolinate works by stimulating the activity of insulin, thus significantly aiding the metabolism of glucose and fat, managing the breakdown of glucose and fat. It also increases sensitivity of insulin receptors.

-Also improved insulin efficiency causes an increase in the production of serotonin, which subsequently reduces appetite.

- In 1968, it was demonstrated that when animals do not receive adequate levels of chromium, insulin is not optimally effective, and damage to insulin-dependent systems can occur. This led the FDA to recommend a daily chromium intake of approximately 130 mcg.

Other actions of chromium include:

· Prevent further fat deposition by burning excess fat leading to decrease in the body weight.

· Enhance penetration of amino acids inside the muscle cells so increase lean body mass.

- Processing destroys much of the chromium content in foods (that can be considered one of the reasons of high obesity percentage in USA).

- It is considered safe with no or little side effects.

- Trivalent ion compounds are used as hexavalent chromium is toxic orally.

- The greatest benefit of chromium picolinate may be its ability to decrease appetite but other claims about burning fats, improving metabolism and increasing muscle mass have no reliable scientific evidences.

2- Caffeine

-Caffeine is a mild stimulant to the central nervous system. It is not addictive, though it can be habit forming.

- Caffeine is a thermogenic agent that stimulates lipolysis, restricts accumulation of fats and increases fat cell capacity to release fats.

- It reduces edema by improving local micro circulation.

- The effect of caffeine on weight loss was examined by Westernp-Plantenga et al (2005). The study concluded that high caffeine consumers reduce weight, fat mass and waist circumference more than low caffeine consumers and placebo consumers.

- Caffeine increases the release of epinephrine into the blood, thus stimulating the release of free fatty acids (disassembled molecules of triglycerides) from fat tissue and/or skeletal muscle

3- Conjugated linoleic acid

- CLA interferes with the enzyme "lipoprotein lipase" that the body uses to move fat from blood to fat cells and enhances the enzyme "hormone-sensitive lipase" which breaks down fats already stored in fat cells, so muscles can burn it, this makes fat cell thinner. It is claimed to result in nutrient partitioning so that ingested calories will be directed to muscles. It is important to monitor cholesterol levels as it may reduce HDL and cholesterol. CLA may help to reduce body fat and increase muscle.

Safety of CLA:

- CLA is a natural nutrient that enhances the immune system, prevents cancer and is of low side effects.

- It was found to increase WBCs count but no long term animal studies of safety. The U.S. Food and Drug Administration (FDA) doesn't test these products to verify the claims listed on manufacturers' labels.

Side Effects : Some people report feeling slightly green or nauseous after taking their CLA, or isolated cases of gastrointestinal upset or loose stools. These side effects typically are reduced when the product is taken with protein (i.e. with milk), and usually decrease after about 2 weeks taking the supplement.

4- Bran:

Bran is the hard fibrous outer layer of grain. It is often produced as a by-product of milling in the production of refined grains.

Bran contains cellulose, polysaccharides and hemicelluloses and is particularly rich in dietary fiber and omegas with significant quantitities of starch, protein, vitamins and dietary minerals.

Bran is a locally acting appetite suppressant that swells in stomach. Fibers, especially the insoluble kind, have good bulking properties. It has an amazing capacity to absorb water and expand. This makes people feel less hunger and that they have eaten a lot, so it can shut down the hunger signals. It can help also to control blood sugar level.

Bran has been used for several decades as a means to end constipation. Its high dietary fiber content helps stools become softer and more bulky. It may work for people with irritable bowel syndrome. We can say that its main use is as bulk laxative.

It should be administrated with large amount of water to avoid intestinal obstruction and shouldn't be taken before sleep.

It is contraindicated in intestinal obstruction. It may decrease the absorption of some concomitantly administrated drugs as Fe, Zn and Ca containing drugs.

Wheat bran has been shown to reduce colon and rectal cancer in rats, which often leads people to assume it will confer the same benefits to humans. In fact, this has not been shown. Other types of bran may provide this beneficial side effect. Specifically rice bran, which is high in antioxidants, may have some cancer prevention abilities.

Also by increasing stool speed, bran ensures that bowel contents don't stagnate, so that means carcinogens, or cancer-causing agents, can't hang around long enough to cause trouble. And if carcinogens are present, a bulkier stool dilutes them.

Herbal products:

Diet Pep :

is a weight loss product with a range of ingredients, including herbs and vitamins. The manufacturers of Diet Pep claim that not only will it help in losing weight but this supplement will also increase the energy levels at the same time. There are two versions of the product available, Diet Pep, and Ultra Diet Pep. Both versions are intended to be taken once or twice a day in tablet form.

The vitamins in this product consist of Calcium, Potassium and Chromium. The herbs in Diet Pep are Ginger Root, Dandelion Root, Green Tea extract and Guarana.

The herbs which are included in Diet Pep are herbs that help reduce appetite and to increase energy levels. The vitamins in this product are classic vitamins that are included in many weight loss pills, like chromium.

The main difference between Diet Pep and the more expensive version of Diet Pep, which is marketed as Ultra Diet Pep, is the addition of the of B6 and B12, which -according to the manufacturers- will also help you beat stress.

Due to the large number of stimulants in this product, Diet Pep could be potentially dangerous to anyone who has a history of stroke, heart attacks or high blood pressure.

Examples of diet pep include:

Diet Pep Ephedra Free:

Guarana, Green Tea, Citrus Aurantium and DynaChrome Chromium

Ultra Diet Pep 2000

Vitamin C, Vitamin B-6, Pantothenic Acid, DynaChrome Chromium, Kola Nut, Siberian Ginseng, Guarana, Wild Yam, Dandelion, Standardized Kelp, Passion flower and Licorice

Another product is Avesil which contains

Clinical Strength Super Citrimax (Burns fat and Decreases appetite)

Green Tea Extract, O-polynicotinate Chromium and Caffeine

1- Ephedra:

It contains the sympathomimetic alkaloid ephedrine. Physiologically, Ephedra stimulates the brain, causing nervousness and making the heartbeat faster. Ephedra temporarily expands the bronchial tubes which make breathing easier.

As a weight loss pill, Ephedrine acts as a natural stimulant of central nervous system increasing energy expenditure through improved hydrolysis of fat, increasing basal metabolic rate and suppressing appetite. Appetite suppression is due to decreasing gastric emptying rate.

Ephedra is best known for its fat burning (thermogenic) properties. It induces thermogenesis by activation of β-receptors. Some research shows the Ephedra promotes fat loss while sparing lean muscle. People also use Ephedra as an energy booster and to help with weight loss.

According to the FDA’s website, the short-term use of Ephedra or Ephedra plus caffeine is associated with a statistically significant increase in short-term weight loss compared to placebo but usage of ephedrine along with caffeine can also be extremely dangerous as caffeine augments the effectiveness of ephedrine.

There are no studies assessing the long-term effects of the use of Ephedra containing dietary supplements. The recommended use of Ephedra is for a short time and not more than 10mg of Ephedra per day.

Adverse effects:

- Cardiovascular: tachycardia, cardiac arrhythmias, Angina pectoris, vasoconstriction with hypertension.

- Gastrointestinal: nausea, vomiting and appetite loss.

- Anxiety, headaches, tremors and insomnia.

Contraindications:

1- Ephedrine should not be used in conjunction with certain antidepressants such as:

- SNRIs (serotonin-norepinephrine re-uptake inhibitors)

- MAOI (Monoamine oxidase inhibitors), as this increases the risk of the above symptoms due to excessive serum levels of norepinephrine.

2- Ephedrine should be used with caution in patients with hypertension, hyperthyroidism, prostatic hypertrophy, diabetes mellitus, cardiovascular disease, during delivery if maternal BP > 130/80 mmHg and lactation.

3- Closed angle glaucoma, phaeochromocytoma, insomnia and anxiety

Due to high incidence of abuse of ephedra, FDA has banned the sale of ephedra in the USA

2- Guarana:

It contains a form of caffeine called guaranine which is 2.5 times stronger than caffeine. It increases the metabolic thermogenesis through stimulation of β-receptors which induce the breakdown and release of stored body fats and thereby allow it to be turned into energy

In the United States, guarana has the status of being generally recognized as safe (GRAS)

Uses: CNS stimulate, weight loss and diuretic

The side effects of guarana would be expected to be similar to those of tea or coffee, such as heartburn, gastritis, insomnia, anxiety and heart arrhythmias (benign palpitations or more serious disturbances of heart rhythm).

Combination products containing guarana and ephedra would be expected to present additional risk.

Interactions:

1- With herbs containing caffeine and black or green tea.

2- With CNS stimulants, Oral contraceptives, MAOI's, diabetes therapy, CNS depressants and theophylline.

Contraindications: Don't use with gastric disease, ulcers, cardiac disease, depression, anxiety, pregnancy/lactating and children.

In a double-blind, placebo-controlled study: the use of guarana plus ephedra for weight loss showed significantly greater weight loss in the treated group than in the placebo group.

3- Gymnema Silvestre:

Gymnema is referred to as gurmar, which means 'sugar killer'.

The hypoglycemic (blood sugar-lowering) action of gymnema is attributed to gymnemic acid which has the same arrangement as glucose molecules and thus competes for glucose receptors in small intestine. That results in decreasing glucose absorption and maintains BSL in diabetes mellitus type ІІ

So we can say that gymnema can reduce glucose absorption from the intestine, improve uptake of glucose into cells and prevent adrenal hormones from stimulating the liver to produce glucose, thereby reducing blood sugar levels.

Dose: Approximately 500-600 milligrams of gymnema Silvestre each day, in 2-3 divided doses. Within the recommended dose it is generally safe and effective Interactions mainly with the hypoglycemic drugs (insulin for example)

4- Siberian ginseng:

Stabilize blood sugar and decrease craving for sweets

It is believed to have adaptogenic properties, which means that it enhances the body’s ability to cope with external stresses (both physical and mental). It commonly used by endurance athletes to enhance stress resistance during intense periods of training. It is considered as a natural energizer.

The most common side effects associated with ginseng are headaches and sleep and gastrointestinal problems. Ginseng may also cause allergic reactions in some users. Not for patient with hypertension, hypoglycemia or heart disease.

5- Dandelion:

The medicinal properties of dandelion (Taraxacum officinale) are varied and essential to overall health.

Weight Loss: dandelion has been used in weight loss trials and produced significant results. Controlled tests on laboratory mice and rats by the same Romanians indicated that a loss of up to 30% of body weight in 30 days was possible when the animals were fed dandelion extract with their food.

It reduces craving for sweets and boosts metabolism. It has high fiber content which is low in calories and slows down digestion so the food stays in the stomach longer and decreases hunger. Some herbal based weight loss pills contain dandelion due to its laxative and diuretic effect (mistake).

Other uses: Lowers Blood Sugar, tonic, gentle diuretic, cleanse your skin and eliminate acne, mild laxative, lower high blood pressure, lower serum cholesterol

People who have a biliary obstruction or cholecystitis should not take dandelion in any form. General side effects include itching, hives and dehydration.

6- Green tea:

The beneficial effects of green tea are attributed to the polyphenols, particularly the catechins, which make up 30% of the dry weight of green tea leaves. Recent studies have suggested a role for catechins especially epigallocatechin gallate (EGCG) in promoting weight loss. Also green tea contains caffeine.

Catechins influence metabolism mainly by increasing thermogenesis (burning of fats) and Suppressing appetite

Animal Studies on a group of female laboratory mice with green tea showed significantly decrease in food intake, body weight gain, and fat mass.

Human Studies: Intake of green tea was found to increase thermogenesis. The thermogenic effect was found to be greater than that due to the amount of caffeine found in the tea. In addition, the excretion of norepinephrine was higher during treatment with the green tea extract than with placebo. This supports the finding that there was an increase in thermogenesis due to increased norepinephrine levels in the body due to sympathetic activation.

7- Kelp:

Kelp refers to several species of large, brown algae. Kelp is a type of seaweed (any type of vegetation growing in the ocean).

Primary chemical constituents of kelp include mucilage, Na alginate, mannitol, beta-carotene, zeaxanthin, bromine, potassium, volatile oils, and many other minerals. Kelp is a good source of many antioxidant vitamins and minerals—especially iodine

Sodium alginate has the unique property of forming a thick gel in water which, when taken orally, can provide laxative effects.

Many of the beneficial properties of kelp have been attributed to its iodine content. Kelp has shown some useful results in the treatment of underactive thyroid glands (hypothyroidism) and goiter. Through the regulation of thyroid function, there is an improvement in all the associated symptoms. Where obesity is associated with thyroid trouble, this herb may be very helpful in reducing the excess weight. Iodine is used to increase metabolism and fat burning properties. It is believed that kelp stimulates a hormone produced by the thyroid gland responsible for boosting metabolism and so help in burning more calories.^4,8

There is no appropriate "therapeutic" dosage of kelp, as it is not yet scientifically proved whether kelp is truly therapeutic for any conditions. However, because of its high iodine content, it is important not to have overdoses of kelp. The recommended daily allowance of iodine is quite small but long term iodine intake could have medical consequences such as hyperthyroidism so the use of kelp for weight loss over a long period of time is not recommended. Also some kelp supplements have been found to contain levels of arsenic high enough to be toxic.

8- Pullulan:

Pullulan is a water soluble, neutral linear polysaccharide consisting of α–1, 6-linked maltotriose residues. It is a fungal exopolysaccharide produced by fermentation of liquefied corn starch by the fungal species Aureobasidium pullulans

It is a slow digesting macromolecule which is tasteless as well as odorless hence it is used as a low-calorie food additive providing bulk and texture.

It has fiber like action and can decreases spikes in blood sugar levels. Pullulan attenuated the postprandial glycemic excursion (movement outward and back or from a mean position)

Recently pullulan is also being investigated for its biomedical applications in various aspects like targeted drug and gene delivery, tissue engineering, wound healing and also even in diagnostic imaging using quantum dots.

9- Passion flower:

It belongs to Passiflora family. It has traditionally been used to combat anxiety.

One component of passionflower -a flavonoid called chrysin- has shown sedative and anti-anxiety effects and in one study of mice it acted similar to a benzodiazepine in preventing induced seizures. Other species of passion flower appear to include somewhat different active compounds, including flavonoids and alkaloids. Main alkaloids are the harmine and harman alkaloids (passiflorine, aribine, loturine, yageine, etc.). Nervous symptoms and cramps that inhibit sleep are alleviated by ingestion of the herb.

Passion flower appears completely nontoxic, and has been approved for food use by the FDA. However Pharmacological investigations in animals indicate that relatively large doses of harman derivatives excite the central nervous system, producing hallucinations and convulsions. Passion flower should be used with caution in conjunction with CNS-depressants or stimulants.

Drugs misused in obesity:

1- Laxatives (stimulant):

Taking laxatives for weight control or weight loss purposes is neither good for fat-loss, nor good for health because:

A) The laxatives increase the bowel (large intestine) activity. Laxatives do not act on the small intestine where most of the calories are absorbed. The actual purpose of taking a laxative is to stimulate the large bowel to empty, which occurs only after the food and calories have been absorbed via the small intestines.

B) Most weight loss is usually fluid-loss leading to electrolyte disorder (blood's potassium level to drop, which may cause heart and/or muscle problems) and dehydration which can be followed by periods of water retention and an appearance of bloating.

C) Prolonged use leads to cramps, bloating, water retention and laxative dependence so when stop the drug the patient will have constipation. Excess use of stimulant laxatives cause severe constipation and pain for long periods (as much as for decades) due to the colon losing its function. It eventually led to surgery removing the colon altogether. It may also cause permanent damage to the gastrointestinal tract (rectal bleeding) and the weakening and softening of the bones, a condition known as osteomalacia.

The reason people seem to lose weight while taking laxatives is usually because they are reducing their caloric intake and food consumption, and/or compulsively exercising.

2- Thyroxin:

A) The body will try to cope with thyroxin by shutting off the normal function of the thyroid gland over time, so upon stopping the tablets patient will not have enough natural thyroxin. It may cause hormonal disturbance and feed back inhibition of thyroid gland.

B) Thyroxin has an effect on every part of the body. It even makes heart muscle go more quickly and induce risk of a whole range of heart problems. Every organ of the body may be affected by an excess of thyroxin.

Some slimy creams containing iodine which is absorbed into the body and increase level of thyroxin.

3- Hypoglycemic drugs:

It will decrease BGL and in diabetic patients may be a risk of hypoglycemic coma.

4- Diuretics:

diuretics will increase water and electrolyte loss leading to dehydration. The weight loss is mainly water and will be regained again when the patient feel thirsty. It will not affect fats. It may be effective for first days but then the body no longer responds to it.

Some times a diuretic is required with herbal products as most of them are thermogenic, increasing sweating and decreasing urine volume, therefore increasing incidence of crystal formation, so diuretics such as Uva ursi are used to increase volume and to avoid crystaluria. E.g. Diet-Booster.

5- Ipecac Syrup:

Many people with eating disorders abuse a syrup called Ipecac to help induce vomiting. Ipecac should only be used in cases of accidental poisoning. Repeated use can cause the heart muscle to weaken. It can cause irregular heartbeats, chest pains, breathing problems, rapid heart rate and cardiac arrest.

Ipecac is very dangerous and it has been the cause of death in many people suffering with an eating disorder.