What is Human Chorionic Gonadotropin (hCG) Diet

Human Chorionic Gonadotropin (hCG) is a natural hormone the body makes during pregnancy. Decades of scientific research have shown that Human Chorionic Gonadotropin (hCG) does not help people who are overweight or obese to lose extra pounds ¹.

hCG diet supplement which stands for human chorionic gonadotropin diet supplement craze was first promoted for weight loss in the 1950s. It faded in the 1970s, especially when it became apparent that there was a lack of evidence to support the use of hCG for weight loss. Most studies have found that hCG has nothing to do with weight loss. It is the super-low-cal diet that is associated with the hCG diet supplement that will result in weight loss.

The hCG diet limits you to 500 calories a day for 8 weeks while taking hCG, either by getting an injection or by taking a “homeopathic” product, such as oral drops, pellets, pills or sprays, which you can buy at the store ¹.

• FDA advises consumers who have purchased homeopathic HCG for weight loss to stop using it, throw it out, and stop following the dieting instructions. Harmful effects should be reported online to FDA’s MedWatch program ² or by phone at 800-FDA-1088 (800-332-1088) and to the consumer’s health care professional.

Products that claim to contain hCG are typically marketed in connection with a very low calorie diet, usually one that limits calories to 500 per day. Many of these popular hCG products claim to “reset your metabolism,” change “abnormal eating patterns,” and shave 20-30 pounds in 30-40 days.

“These products are marketed with incredible claims and people think that if they’re losing weight, hCG must be working,” says the acting director of FDA’s Division of Non-Prescription Drugs and Health Fraud. “But the data simply does not support this; any loss is from severe calorie restriction. Not from the hCG.”
(Source ³).

People lose weight on the hCG diet not because of the Human Chorionic Gonadotropin hormone, but from the very low calorie they’re only eating, about 500 calories per day on the diet.

• In general, women need 1,600 to 2,400 calories per day and men need 2,000 to 3,000 calories per day to maintain a healthy weight.

Many research studies have shown that hCG does not move fat away from problem areas in the body or decrease the feeling of hunger that goes with low calorie
diets.

Following a healthy diet when eating only 500 calories a day is possible. But eating so few calories could be unsafe and should be done only under a medical guidance and supervision. Even if you’re not dieting, using hCG could be harmful.

hCG is approved by FDA as a prescription drug for the treatment of female infertility, and other medical conditions. It is not approved for weight loss. hCG helps a woman’s eggs to mature and be released from the ovaries. In fact, the prescription drug label notes there “is no substantial evidence that it increases weight loss beyond that resulting from caloric restriction, that it causes a more attractive or ‘normal’ distribution of fat, or that it decreases the hunger and discomfort associated with calorie-restricted diets.”

Health care providers understand that hormones are powerful and must be prescribed with caution. A bit too much or too little of any hormone can result in health problems. For this reason, doctors must keep a close watch on treatments that affect hormone levels.

hCG is not approved for OTC sale for any purpose.

** HCG Diet Products Are Illegal (source ³).

The Food and Drug Administration (FDA) is advising consumers to steer clear of these “homeopathic” human chorionic gonadotropin (HCG) weight-loss products. They are sold in the form of oral drops, pellets and sprays and can be found online and in some retail stores.

FDA and the Federal Trade Commission have issued seven letters to companies warning them that they are selling illegal homeopathic HCG weight-loss drugs that have not been approved by FDA, and that make unsupported claims.

A hCG Diet is a Potentially Dangerous Diet

Living on 500 calories a day is not only unhealthy—it’s hazardous, according to FDA experts. Consumers on such restrictive diets are at increased risk for side effects that include gallstone formation, an imbalance of the electrolytes that keep the body’s muscles and nerves functioning properly, and an irregular heartbeat ¹.

A nutritionist at FDA’s Center for Food Safety and Applied Nutrition, echoes concerns about such restrictive diets. They can be dangerous, she says, and potentially fatal.

Very low calorie diets are sometimes prescribed by health care professionals for people who are moderately to extremely obese as part of medical treatment to lessen health conditions caused by obesity, like high blood pressure. But even then, strict—and constant—medical supervision is needed to ensure that side effects are not life threatening.

Without medical oversight, consumers on very low calorie diets may not be getting enough vitamins, minerals and most critically protein.

• FDA advises consumers who have purchased homeopathic HCG for weight loss to stop using it, throw it out, and stop following the dieting instructions. Harmful effects should be reported online to FDA’s MedWatch program ² or by phone at 800-FDA-1088 (800-332-1088) and to the consumer’s health care professional.

Risks of Injected hCG ¹

Women

• irregular periods and
• vaginal bleeding
• ovarian cysts
• blood clots
• breast tenderness
• headaches
• possible increased long-term risk of breast cancer for pre-menopausal women

Men

• breast enlargement
• breast tenderness
• blood clots
• decreased sperm production and infertility

Doctors worry that injectable hCG—which can affect sex hormones in both men and women—can cause harmful or unexpected effects.

Doctors also worry that hCG might not be safe in those with liver, kidney, or heart disease.

hCG Dietary Supplements ¹

hCG is a protein, so it is broken down as food when taken by mouth. This process makes it inactive, meaning the hCG contained in drops and pills will have no effect on the body.

A homeopathic form of hCG is sold widely as an over-the-counter supplement. Homeopathy seeks to trigger the body to heal itself by giving very small doses of highly diluted substances. Most homeopathic products are so diluted that none of the healing substance—in this case,  no hCG remains.

Whether or not an over-the-counter product actually contains hCG, doctors have concerns about the safety of dietary supplements. The FDA does not regulate food supplements the way it regulates prescription drugs. So trying to figure out if a particular product is safe can be confusing.

Internet sites selling hCG products online, for example, often do not list the ingredients in their product. Even when ingredients are clearly listed on the package, there is no guarantee that the contents are exactly what the package says. Supplements can contain too much or too little of the ingredient you want—or none at all. They can contain potentially harmful substances that aren’t listed on the label. Even a product labeled “natural” is not necessarily safe.

The FDA ⁴ and the Federal Trade Commission ⁵ recently warned companies that sell homeopathic hCG products that they are breaking the law by selling drugs that have not been approved, and by making unproven claims about their effects. The FDA and FTC also caution that these products may be unsafe.

What about the 500-calorie diet ?

A 500-calorie diet makes it hard to meet your nutritional needs. You need more than 40 different nutrients for good health and should be eating 5 to 9 servings of fruits and vegetables a day. Multivitamins are not a solution to eating a poor diet. A very low-calorie diet can also cause gallstones, an irregular heartbeat, and other health problems.

Some people with health problems related to their weight might be candidates for a very low-calorie diet, but they must be carefully supervised by a health professional.

What You Can Eat and What You Can’t

You won’t be eating much. The diet lets you have two meals a day, lunch and dinner. Each meal has to include one protein, one vegetable, one bread, and one fruit.

You can broil or grill veal, beef, chicken breast, fresh white fish, lobster, crab, or shrimp as long you don’t eat any visible fat. No salmon, eel, tuna, herring, or dried or pickled fish are allowed.

Vegetable choices include spinach, chard, chicory, beet greens, green salad, tomatoes, celery, fennel, onions, red radishes, cucumbers, asparagus, and cabbage.

Bread can be one bread stick or one piece of melba toast.

For fruit, you can choose an orange, an apple, a handful of strawberries, or half a grapefruit. The diet allows as much water, coffee, and tea as you want. You can also have up to 1 tablespoon of milk per day.

You can use sugar substitutes but not sugar to sweeten drinks. Butter and oils aren’t allowed.

Losing Weight Safely

Doctors agree that the best way to lose extra pounds and keep them off is to eat a healthy diet with plenty of whole grains, vegetables—including legumes like peas and beans and fresh fruits, and to limit fried foods or fatty meat products. Drinking water instead of sugary sodas and being sure to exercise for 30 minutes a day, most days of the week, are also key.

References

1. The Hormone Health Network. hCG Diet. http://www.hormone.org/hormones-and-health/myth-vs-fact/hcg-diet
2. US Food and Drug Administration. MedWatch: The FDA Safety Information and Adverse Event Reporting Program. https://www.fda.gov/Safety/MedWatch/default.htm
3. US Food and Drug Administration Warning: https://www.fda.gov/forconsumers/consumerupdates/ucm281333.htm
4. US Food and Drug Administration. HCG Diet Products Are Illegal. https://www.fda.gov/forconsumers/consumerupdates/ucm281333.htm
5. Federal Trade Commission. Joint FDA/FTC Warning Letter Concerning Product Labeling of Human Chrorionic Gonadotropin (HCG) Drugs. https://www.ftc.gov/public-statements/2011/11/joint-fdaftc-warning-letter-concerning-product-labeling-human-chrorionic

Caffeine and Weight Loss

Caffeine is a widely consumed stimulant, which can be consumed in several forms (e.g. coffee, energy drinks, etc.), is one of the most commonly used psychoactive substance worldwide ¹. Recent data from nationally representative samples indicate about 89% of American adults consume caffeinated products daily with virtually no difference between men and women in how frequently the products are used ². Caffeine is a naturally occurring alkaloid substance found in numerous plant species with coffee beans, tea leaves, cocoa beans, and kola nuts are the primary natural sources of this compound ³. Caffeine is added to numerous foods and beverages (e.g., soft drinks and energy drinks). Chocolate and cocoa ⁴ are also sources of caffeine, as are certain dietary supplements ⁵ and medications ⁴.

There has been some concern regarding the potential adverse health effects of caffeine, especially with regard to cardiovascular disease and diabetes mellitus risk ⁶. Acute caffeine consumption increases blood pressure and plasma lipids, and these effects led to speculation that chronic caffeine consumption would increase cardiovascular disease risk ⁷; however, epidemiological studies have generally concluded that caffeine consumption is not associated with higher cardiovascular risk ⁸. Short-term metabolic studies have suggested caffeine has adverse effects on glucose tolerance and whole-body glucose management ⁹ which could increase diabetes risk, but longer-term investigations found that coffee consumption was associated with a lower risk of Type 2 diabetes ¹⁰. Other studies suggested there were positive effects of caffeinated products, including reduced liver dysfunction ¹¹, slower age-related cognitive declines ¹², improvement in some types of athletic performances ¹³, and reduced intensity of exercise-induced delayed onset muscle soreness ¹⁴. A comprehensive review of the health effects of caffeine concluded that adult consumption ≤400 mg/day (6 mg/kg body weight for a 65 kg person) was not associated with adverse effects on cardiovascular health, bone status, male reproductive systems, adult behavior, or cancer risk, although it was recommended that women of reproductive age should consume <300 mg/day because of possible effects on fertility and conception ¹⁵.

Caffeine is generally regarded as a safe substance and has a very long history of use. A comprehensive review of the effects of caffeine consumption on human health, commissioned by Health Canada, concluded that for the healthy adult population, moderate chronic intakes of caffeine up to 400 mg/d are not associated with adverse effects on cardiovascular health, calcium balance and bone status, behavior, cancer risk, and male fertility ¹⁶. Several recent meta-analyses support these conclusions ¹⁷, ¹⁸. However, it was suggested that women planning to become pregnant, as well as pregnant and lactating women, limit caffeine ingestion to ≤300 mg/d because of some evidence that caffeine consumption may adversely affect fertility and fetal growth ¹⁹.

Recommended Maximum Caffeine Intake Levels for Children and Women of Childbearing Age Children ¹⁶:

• 4 – 6 years 45 mg/day
• 7 – 9 years 62.5 mg/day
• 10 – 12 years 85 mg/day

Women who are planning to become pregnant, pregnant women and breast feeding mothers ¹⁶:

• 300 mg/day

Caffeine is considered a diuretic during periods of rest which results in a greater volume of fluid loss through urine ²⁰. For instance, a study conducted by Neuhäuser-Berthold et al. ²¹ demonstrated a loss in total body water of approximately 1.1 kg following the consumption of a 321 mg serving of caffeine in the form of coffee in the morning and afternoon. Moreover, Passmore et al. ²² examined the effects of early day caffeine consumption on urine output in several doses (45, 90, 180, and 360 mg) and found a statistical difference following the highest dose. Caffeine’s role as a diuretic is relatively understood, but it is unclear if caffeine consumption truly burns more calories, and increases the breakdown of fat.

Caffeine is frequently added to dietary supplements with claims it facilitates weight loss. The labels of supplements that contain caffeine don’t always list it, so you might not know if a supplement has caffeine.

In humans, caffeine has been shown to stimulate thermogenesis and fat oxidation ²³, ²⁴, ²⁵. In humans caffeine stimulates thermogenesis by unknown mechanisms and it is hypothesized that lactate and triglyceride production and increased vascular smooth muscle tone may be responsible for the major part of the thermogenic effect of caffeine ²⁴. The magnitude of thermogenesis was smaller in obese (4.9 +/- 2.0%) than in lean subjects (7.6 +/- 1.3%) ²⁵. The thermogeneic response to caffeine was prolonged during the night in lean women only. The coffee-induced stimulation of energy expenditure was mediated by a concomitant increase in lipid and carbohydrate oxidation. The magnitude of this effect was, however, blunted in obese women (lipid oxidation increased by 29 and 10% in lean and obese women, respectively) ²⁵. Despite the high levels of urinary methylxanthine excretion, thermogenesis and lipid oxidation were less stimulated in obese than in lean subjects ²⁵.

More recently it has been shown caffeine affects the thermogenesis by inhibiting the enzyme phosphodiesterase ²⁶. This enzyme degrades intracellular cyclic amino mono phosphate ²⁷. Phosphodiesterase usually hydrolyses cyclic adenosine monophosphate (cAMP) to AMP, but after consumption of caffeine, cAMP concentration rises and sympathetic nerve system activity will be increased and inactive hormone-sensitive lipase will be activated, which promotes lipolysis ²⁸. The sympathetic nerve system activity and lipoysis are dependent on cAMP, because cAMP activates the protein kinase A ²⁹. Besides the inhibition of phosphodiesterase, caffeine also affects the thermogenesis through the stimulation of substrate cycles such as the Cori-cycle and the free fatty acid-triglyceride cycle ³⁰. Caffeine is a methylxanthine, which has a thermogenic impact. In the Cori cycle, lactate moves from the muscles to the liver, where it will be converted into pyruvate. The pyruvate will be converted to glucose by the enzyme lactate dehydrogenase and circulate back to the muscles through the blood ³⁰. Acheson et al. ²⁸ showed that free fatty acids turnover and lipid oxidation are increased after the consumption of caffeine but that it requires a large increase in free fatty acids turnover to have a small increase in lipid oxidation. Nonoxidative lipid turnover, the hydrolysis and reesterification of triacylglycerol, is greater than the increase in oxidative lipid disposal ²⁸. They also found that caffeine antagonizes the inhibitory effects of adenosine on lipolysis by adenylyl cyclase. Nonadrenergic thermogenic mechanisms can also be involved, as caffeine antagonizes the ryanodine receptor, the calcium ion release channel of sarcoplasmatic reticulum in skeletal muscle that for instance increases glycolysis and adenosine triphosphate turnover after stimulation ²⁸.

Caffeine inhibit two enzymes, which interrupt the pathway of norepinephrine-activated thermogenesis ³¹. As sympathetic nerve system activity is determined by the concentration of norepinephrine, more norepinephrine means a higher activity and increased energy expenditure. Sympathetic nerve system activity regulates the resting metabolic rate, which is the largest component of the daily energy expenditure. Norepinephrine makes it possible to increase the usage of adenosine triphosphate (ATP) through ion pumping and substrate cycling ³². The rate of mitochondrial oxidation is also involved in the increased thermogenesis due to the poor coupling of adenosine triphosphate (ATP) synthesis, which leads to heat production. Gene expression of the uncoupling proteins also increases when cAMP activates the protein kinase A, after the inhibition of phophodiesterase by caffeine ³³. The protein kinase A stimulates hormone-sensitive lipase, which increases the concentration of free fatty acids by the conversion of triglycerides. Uncoupling proteins activity will be enhanced through this ³³.

Single-dose oral administration of 100 mg caffeine increased the resting metabolic rate of both lean and postobese human volunteers by 3–4% over 150 min and improved the defective diet-induced thermogenesis observed in the postobese subjects ²³. Measurements of energy expenditure in a room respirometer indicate that repeated caffeine administration (100 mg) at 2-h intervals over a 12-h day period increased the energy expenditure of both subject groups by 8–11% during that period but had no influence on the subsequent 12-h night energy expenditure ²³. The net effect was a significant increase in daily energy expenditure of 150 kcal in the lean volunteers and 79 kcal in the postobese subjects. Caffeine at commonly consumed doses can have a significant influence on energy balance and may promote thermogenesis in the treatment of obesity ²³.

Caffeine ³⁴, ³⁵, ³⁶, ³⁷ has been shown to increase energy expenditure in humans, and weight loss has reduced risk factors for diabetes in clinical trials ³⁸. Consequently, it seems possible that both coffee and tea consumption may decrease diabetes risk by helping individuals control their body weight. However, in a small study involving fifty healthy adults aged 18 to 50 years (42% male) where participants consumed a beverage containing 0, 1, or 3 mg/kg caffeine (order randomized). Thirty minutes later, participants consumed a buffet breakfast, ad libitum. After leaving the laboratory, participants completed hourly appetite assessments and dietary habit books until midnight or bedtime. The study results suggest caffeine has weak, transient effects on energy intake and do not support caffeine as an effective appetite suppressant ³⁹.

Caffeine may also slightly boost weight loss or prevent weight gain, but there’s no sound evidence that increased caffeine consumption results in significant or permanent weight loss ⁴⁰.

Efficacy of caffeine

For many years caffeine is known for its stimulating properties and the thermogenic effects have been extensively examined. Besides enhancing energy expenditure, caffeine also affects energy intake. However, these acute effects have not resulted into a successful long-term approach yet (Table 1) ⁴¹. Only in a prospective study from Lopez-Garcia et al.,69 who studied the effect of caffeine on long-term weight change in a cohort, it was found that people who increased the caffeine consumption over 12 years gained less weight than those who decreased the caffeine consumption. Previous studies suggest that sensitivity to caffeine may be lost over time, which means that body weight regulation cannot be sustained for a longer period of time while receiving the same dosage.

Table 1: Short-term and long-term studies with caffeine

Author	Year	Duration (hours or weeks)	Sample size (n)	BMI (kg/ m2)	Gender	Age (years)	Dosage (mg)	Outcome
Short-term study
Acheson et al.42	1980	3	CAF=27	18–30	M/F	21–35	CAF=300–600	Increase in EE in normal weight (10–16%) and obese subjects; however, only increase in fat oxidation in normal weight subjects
Tremblay et al 43	1988	1.5	CAF=20	21.5	M/F	20.8	CAF=300	Decrease in energy intake in men (21.7%)
Dulloo et al.44	1989	2.5/24	CAF=18 and 11	26.1–29.6	M/F	20–35	CAF=100 and 600	Increase in EE after 2.5 h (3–4%) and 24 h (8–11%); net increase in lean subjects 150 kcal and postobese 79 kcal
Astrup et al.30	1990	3	CAF=6	21.9	M/F	20–32	CAF=100, 200 and 400	Net increase in EE after 100 and 400 mg of 27.6 and 97.2 kcal
Bracco et al.45	1995	24	CAF=20	<25 and 25>	F	20–35	CAF=500	Increase in EE and lipid oxidation in lean (7.6; 29%) and obese subjects (4.9; 10%)
Arciero et al.46	1995	1.5	CAF=20	25.1	M	19–80	CAF=300–350	Increase in EE of 9.5–11%
Dulloo et al.47	1999	24	CAF=10	25.1	M	25	CAF=150	No difference in EE between caffeine and placebo group
Hollands et al 48	2001	2	CAF=12	22.3	M/F	20–46	CAF=100	Increase in EE of 16%
Rumpler et al.49	2001	23	CAF=12	18–30	M	25–60	CAF=270	Increase in EE of 3.4%=331 kJ day−1
Acheson et al.28	2004	4	CAF=8	25.5	M	23.1	CAF=770	Increase in EE of 13.3%
Gregersen et al.50	2009	13.5	CAF=15	22.4	M	23.6	CAF=150	No significant difference in EE between caffeine and placebo group
Long-term study
Pasman et al.41	1997	56	CAF=13	31.2	F	34.8	CAF=100 per day	No weight maintenance (+66.1% body weight regain)

Abbreviations: CAF = caffeine; EE = energy expenditure; BMI = body mass index; M = male; F = female.

[Source ⁵¹]

Caffeine Supplements

Caffeine is one of the ingredients now being included in many of the weight loss supplements. It’s added for its energy enhancement, appetite suppressant, and “fat-burning” properties.

On September 1, 2015, the FDA issued warning letters to five distributors of pure powdered caffeine because these products are dangerous and present a significant or unreasonable risk of illness or injury to consumers. (Source ⁵²). Pure powdered caffeine products are potentially dangerous and have contributed to at least two deaths ⁵³. The FDA advises consumers to avoid pure powdered caffeine. It is nearly impossible to accurately measure pure powdered caffeine with common kitchen measuring tools and you can easily consume a lethal amount.

The difference between a safe amount and a toxic dose of caffeine in these pure powdered products is very small. Safe quantities of these products can be nearly impossible to measure accurately with common kitchen measuring tools. Volume measures, such as teaspoons, are not precise enough to calculate how many milligrams of caffeine are in the serving size. Pre-existing conditions can intensify the effects of caffeine and make the product more dangerous for these individuals.

One teaspoon of pure powdered caffeine (100 percent caffeine) is equivalent to the amount of caffeine in about 28 cups of regular coffee. While consumers of caffeinated products such as coffee, tea, and soda may be aware of caffeine’s less serious effects – such as nervousness and tremors – they may not be aware that these pure powdered caffeine products are much more potent and can cause serious health effects, including rapid or dangerously erratic heartbeat, seizures and death. Vomiting, diarrhea, stupor and disorientation are also symptoms of caffeine toxicity.

 

Does caffeine work ?

In a prospective cohort study ⁵⁴ to assess the effect of weight change on the relationship between coffee and tea consumption and diabetes risk. The finding of that study found that for less than or equal to 60-years-old subjects, the risk of diabetes was significantly, negatively and independently associated with the consumption of ground-caffeinated coffee, ground-decaffeinated coffee and regular tea offers clues to the underlying causes of the reduction in diabetes risk. It suggests that each of these beverages contains constituents that are involved in reducing diabetes risk, and that are not contained, or not active, in the other two beverages. Caffeine appears to have been involved in the reduction of diabetes risk, possibly by inducing weight loss, because: (1) caffeine accounted for the significance of the negative association between diabetes risk and ground-caffeinated coffee, after the effects of ground-decaffeinated coffee and regular tea had been considered; (2) caffeine also accounted for the significance of the negative association between weight gain and ground-caffeinated coffee, after the effects of ground-decaffeinated coffee had been considered; and (3) the negative association between caffeine intake and diabetes risk was only significant for subjects with prior weight loss. These findings are consistent with the finding in several previously-published studies that caffeine induces thermogenesis ³⁴, ⁵⁵, ³⁶ and stimulates lipid oxidation ³⁴, ³⁶, ³⁷  in humans. Caffeine might thereby help individuals control their weight, and hence decrease diabetes-risk.

In addition, some studies found that even decaffeinated coffee may contribute to modest weight loss, suggesting that substances or factors besides caffeine may play a role in weight loss.

A series of four trials ⁵⁶ was carried out to investigate the effects of caffeine and coffee on the metabolic rate and substrate utilization in normal weight and obese individuals. In the first trial 8 mg/kg caffeine was compared with a placebo in normal weight subjects. Metabolic rate increased significantly during the 3 hr after caffeine ingestion. While plasma glucose, insulin, and carbohydrate oxidation did not change significantly, plasma free fatty acid levels rose from 432 +/- 31 to 848 +/- 135 muEq/liter and were accompanied by significant increases in fat oxidation during the last hour of the test. In the second and third trials the effects of coffee providing 4 mg/kg caffeine were studied in control and obese subjects. Metabolic rate increased significantly in both groups; however, significant increases in fat oxidation were only observed in the control group. Plasma free fatty acids did not change in the obese. In the fourth trial, coffee was taken with a 3080 kJ meal. The thermic effect of the meal was significantly greater after coffee than after decaffeinated coffee and again fat oxidation was significantly greater after coffee. In conclusion caffeine/coffee stimulates the metabolic rate in both control and obese individuals; however, this is accompanied by greater oxidation of fat in normal weight subjects. Weight-loss dietary supplements with caffeine might help you lose a little weight or gain less weight over time. But when you use caffeine regularly, you develop a tolerance to it. This tolerance might lessen any effect of caffeine on body weight over time.

Although research about the connection between caffeine and weight isn’t definitive, there are a few theories about how caffeine might affect weight, including:

• Appetite suppression. Caffeine may reduce your desire to eat for a brief time, but there’s not enough evidence to show that long-term consumption aids weight loss.
• Calorie burning. Caffeine may stimulate thermogenesis — one way your body generates heat and energy from digesting food. But this probably isn’t enough to produce significant weight loss.

It is possible that subjects with weight loss, and hence lower diabetes risk, were also, coincidentally, prone to drinking ground coffee and regular tea, and that the prior weight loss caused the negative association between these beverages and diabetes risk. However, given that previous studies have yielded evidence supporting the weight-reduction potential of both regular tea ³⁴ and caffeine ³⁴, ³⁶, ³⁷ it seems more likely that the beverages themselves promoted the weight loss and hence the reduction in diabetes risk. In addition, some studies found that even decaffeinated coffee may contribute to modest weight loss, suggesting that substances or factors besides caffeine may play a role in weight loss.

The bottom line: Be cautious about using caffeine products to help with weight loss. When used in moderation (400 milligrams or less) by healthy adults, caffeine is generally safe. But too much caffeine might cause nervousness, insomnia, nausea, increased blood pressure and other problems.

Also keep in mind that some caffeinated beverages, such as specialty coffees, are high in calories and fat. So instead of losing weight, you might actually gain weight if you drink too many of these.

Safety of caffeine

Caffeine is safe at low doses. But it can make you feel nervous, jittery, and shaky. It can also affect your sleep. At high doses (above about 400 milligrams [mg] a day for adults), it can cause nausea, vomiting, rapid heartbeat, and seizures. Combining caffeine with other stimulant ingredients can increase caffeine’s effects.

Caffeine is found in many beverages, including coffee, tea, energy drinks and colas; in products containing cocoa or chocolate; and in a variety of medications and dietary supplements, including supplements aimed at weight loss.

Caffeine appears to be a safe thermogenic agent for weight control. In adults, the short-term lethal dose for caffeine is estimated at 5–10 g per day (either intravenously or orally), which is equivalent to 75 cups of coffee, 125 cups of tea or 200 cola beverages ⁵⁷. Long-term ingestion of caffeine has been suggested to have some minor adverse effects on human health. Astrup et al. ³⁰ observed only small and insignificant changes in blood pressure and pulse rate after 100 and 200 mg caffeine. In contrast, 400 mg caffeine significantly increased systolic and diastolic blood pressure by an average value of 6.3 mmHg. Furthermore, after 400 mg caffeine, significantly more subjects reported side effects such as palpitation, anxiety, headache, restlessness, dizziness compared with placebo ³⁰. Robertson et al. ⁵⁸ administrated 250 mg oral caffeine to nine subjects who were not used to coffee. Systolic blood pressure increased 10 mmHg 1 hour after caffeine consumption. Heart rate showed a decrease after the first hour followed by an increase above baseline after 2 hours ⁵⁸. However, in a subsequent study that examined the chronic effects of caffeine ingestion (150 mg day−1 for 7 days), tolerance to these effects was developed after 1–4 days ⁵⁹. Thus no long-term effects of caffeine on blood pressure, heart rate or plasma rennin activity were demonstrated. Furthermore, in the short term, Bracco et al. ⁴⁵ did not find a significantly altered heart rate during the day after 4 mg caffeine per kg body weight was consumed five times daily. Accordingly, the use of caffeine is relatively safe, as it is quite certain that, although acute caffeine consumption may alter some cardiovascular variables, chronic ingestion of caffeine has little or no health consequences.

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4. Heckman MA, Weil J, Gonzalez de Mejia E. Caffeine (1, 3, 7-trimethylxanthine) in foods: a comprehensive review on consumption, functionality, safety, and regulatory matters. J Food Sci 2010;75:R77–87.
5. Andrews KW, Schweitzer A, Zhao C, Holden JM, Roseland JM, Brandt M, Dwyer JT, Picciano MF, Saldanha LG, Fisher KD, et al. The caffeine contents of dietary supplements commonly purchased in the US: analysis of 53 products with caffeine-containing ingredients. Anal Bioanal Chem 2007;389:231–9.
6. Knapik JJ, Trone DW, McGraw S, Steelman RA, Austin KG, Lieberman HR. Caffeine Use among Active Duty Navy and Marine Corps Personnel. Nutrients. 2016;8(10):620. doi:10.3390/nu8100620 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084008/
7. Cai L., Ma D., Zhang Y., Lui Z., Wang P. The effect of coffee consumption on serum lipids: A meta-analysis of randomized controlled trials. Eur. J. Clin. Nutr. 2012;66:872–877. doi: 10.1038/ejcn.2012.68
8. Wilson P.W.F., Bloom H.L. Caffeine consumption and cardiovascular risk: Little cause for concern. J. Am. Heart Assoc. 2016;5:e003089. doi: 10.1161/JAHA.115.003089
9. Shearer J., Graham T.E. Performance effects and metabolic consequences of caffeine and caffeinated energy drink consumption on glucose disposal. Nutr. Rev. 2014;72:121–136. doi: 10.1111/nure.12124
10. Ding M., Bhupathiraju S.N., Chen M., VanDam R.M., Hu F.B. Caffeinated and decaffeinated coffee consumption and risk of Type 2 diabetes: A systematic review and a dose-response meta-analysis. Diabetes Care. 2014;37:569–586. doi: 10.2337/dc13-1203 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898757/
11. Feld J.J., Lavoie E.G., Fausther M., Dranoff J.A. I drink for my liver, doc: Emerging evidence that coffee prevents cirrhosis. F1000Research. 2015;4:95. doi: 10.12688/f1000research.6368.2
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Weight Loss and Diet Pills Review

More than two-thirds of adults and one-third of children in the United States are overweight or obese. Obesity or being overweight may increase the risk of many health problems, including type 2 diabetes, heart disease, and certain cancers. If you’re pregnant, excess weight may lead to short- and long-term health problems for you and your child. Achieving a healthy weight, eating a healthy diet, and being physically active can help prevent these weight-related diseases.

Some people, in their efforts to lose weight, turn to unproven dietary supplements (sometimes marketed as “fat burners” or appetite suppressants), which can have harmful side effects. If you’re thinking about starting a new weight-loss program, talk with your health care provider, who can assess your weight and health risks, determine whether you need to lose weight, and provide information that will help you make informed decisions about an effective weight-loss program.

The use of weight loss supplements for weight loss has become increasingly popular, as reflected by the $55.4 billion spent in the U.S. in 2006 for weight loss and diet control and on more than 85,000 different combinations of vitamins, minerals, botanicals, amino acids, probiotics, and other supplement ingredients ¹, ². Based on a study by the National Center for Complementary and Alternative Medicine, 36% of adults ³ and 1 in 10 teens ⁴ are using some form of weight loss supplements at some point in their lives, which rises to 62% when including megavitamins or prayer. Dietary supplements can easily be purchased by people of all ages at pharmacies, grocery stores, health food stores, gyms, and other retailers. And unlike prescription medications, supplements do not require premarketing approval before they reach store shelves. Under the Dietary Supplement Health and Education Act of 1994, anything labeled as a dietary supplement is assumed to be safe until proven otherwise. The FDA is charged with the unenviable task of identifying and removing dangerous supplements only after they have caused harm. Although dietary and herbal supplements are governed under the Dietary Supplement Health and Education Act of 1994, weight loss supplements are not presently regulated by the U.S. Federal Drug Administration and the safety profiles of many are unknown ⁵, ⁶. And potentially dangerous supplements are widely available ⁷.

More than 500 supplements have already been found to be adulterated with pharmaceuticals or pharmaceutical analogues, including new stimulants, novel anabolic steroids, unapproved antidepressants, banned weight-loss medications, and untested sildenafil analogues ⁸. In 2013 alone, researchers discovered two new stimulants in widely marketed supplements. Researchers have identified a new analogue of methamphetamine, N,α-diethyl-phenylethylamine (N,α-DEPEA), in a popular sports supplement ⁹. FDA scientists discovered another stimulant, β-methylphenethylamine (β-MePEA) — a novel analogue of amphetamine — in nine supplements ¹⁰. N,α-DEPEA and β-MePEA have never been studied in humans, and their adverse effects are entirely unknown; yet they are sold as “natural” products without having undergone any premarketing testing for safety. Although supplements containing N,α-DEPEA were voluntarily withdrawn from the market, supplements containing β-MePEA remain widely available. ⁷.

Epidemiologists at the Centers for Disease Control and Prevention recently confirmed what an astute liver-transplant surgeon in Honolulu already suspected: OxyElite Pro, a popular over-the-counter supplement, was responsible for a cluster of cases of severe hepatitis and liver failure ¹¹. Although patients began to develop severe hepatitis in May 2013, the Food and Drug Administration (FDA), whose job it is to remove dangerous supplements from store shelves, did not learn of the cases until mid-September, 4 months later. By February 2014, the CDC had linked 97 cases, resulting in 47 hospitalizations, three liver transplantations, and one death, to OxyElite Pro. This dietary supplement was recalled, but nothing has been done to prevent another supplement from causing organ failure or death. Nor have any changes been made to improve the FDA’s ability to detect dangerous supplements ⁷.

The Dangers of Over-the-Counter Diet Pills and Muscle-Building Dietary Supplements

The American Academy of Pediatrics is strongly opposed to the use of supplements for weight loss and muscle building in adolescents ¹², ¹³. Yet a national survey found that 11% of teens had ever used a weight loss supplement. In the same survey, 5% of teens had used creatine, one of many dietary supplements sold for muscle building.

Research shows that dietary supplements sold for weight loss and muscle building often contain drugs that are prescription-only, illegal, or untested for human use. This can lead to serious health risks, including stroke, testicular cancer, severe liver injury, and even death ¹⁴, ¹⁵, ¹⁶, ¹⁷.

The rate of liver failure caused by dietary supplements has risen 185% in the past decade ¹⁸. In the United States, 16% of cases of serious drug-induced liver injury are attributed to dietary supplements. The vast majority are those sold for weight loss and muscle building ¹⁹.

Drugs found in supplements for weight loss and muscle building have included:

• The active ingredient in Meridia, a prescription weight-loss drug pulled from the market in 2010 ²⁰,
• Drugs that have been designed to be chemically similar to methamphetamine (aka speed) ²¹,
• Antidepressants such as fluoxetine, the active ingredient in Prozac ²²,
• Anabolic steroids and precursor chemicals, which can cause young athletes to fail doping tests and have been associated with testicular cancer ²³,

Many supplements whose labels say they contain “pro-hormones,” “natural steroids,” or “testosterone boosters” actually contain designer anabolic steroids–with dangerous consequences. Use of these compounds through dietary supplements is widespread. In younger men, these supplements may be a common cause of liver injury, problems with bile secretion, testicular disorders, growth of breast tissue, and infertility. Authors advise against dietary supplement use, especially those known or suspected to contain designer steroids ²⁴.

Recalls are not enough to protect people from supplements containing unlisted, unapproved ingredients. In November 2009, the U.S. Food and Drug Administration banned Pai You Gou, a dietary supplement sold for weight loss, after detecting at least two banned pharmaceutical compounds, sibutramine and phenolphthalein, in this product. Sibutramine and phenolphthalein have serious and well-documented side effects. But almost a year after the recall, nearly one in four Brazilian-born Massachusetts women were still using this product ²⁵.

Dietary supplements marketed for weight loss and muscle building have dangerous side effects, including hepatitis and liver failure. The U.S. Centers for Disease Control and Prevention documented a series of severe acute hepatitis (liver injury) and liver failure of unknown cause. Of the 29 confirmed cases of acute hepatitis and liver failure, 24 patients reported using OxyELITE Pro, a dietary supplement sold for weight loss and muscle gain, within 60 days before illness onset ²⁶. Dangerous stimulants are often found in widely available supplements for weight loss and muscle building. When one stimulant is banned, supplement makers often continue using the banned substances, or replace them with a related chemical. Many of these chemicals have never been tested for safety in humans.

Researchers found N,α-DEPEA, in a widely available muscle-building supplement. N,α-DEPEA is a banned and potentially dangerous designer stimulant closely related to methamphetamine ²⁷.

Half of supplements marketed as containing the herbal ingredient acacia rigidula were found to contain β-methylphenylethylamine (BMPEA). BMPEA is a stimulant that has not been assessed for safety or efficacy in humans. It is closely related to the banned compound DMAA, which has been associated with several deaths ²⁸.

Another DMAA substitute, 1,3-dimethylbutylamine (DMBA), has also been banned by the FDA. Despite the ban, researchers found at least a dozen supplements to contain DMBA in dosages ranging from 13 to 120 mg per serving ²⁹.

Muscle-building supplements may lead to increased risk of testicular germ cancer in men. A study of nearly 1000 men found that men who developed testicular germ cancer had used more muscle-building supplements than similar men who did not develop testicular germ cancer. The association was particularly strong among early users, long-term users, and use of two or more types of muscle-building supplements ³⁰.

Diet pills may block the function of other drugs, including cancer treatments. Diet pills may also be associated with organ toxicity. Research suggests that the diet drug orlistat limits the function of a kind of protein, CES2, needed to activate a common cancer drug, PPD. Orlistat has also been associated with gastrointestinal issues, as well as liver toxicity ³¹.

Diet pills may decrease users’ vitamin D levels. Researchers found that adolescent participants’ vitamin D levels decreased after one month of taking orlistat, despite participants also taking a multivitamin daily. Vitamin D is important for bone health, cell growth, and immune function ³².

Diet pills could be abused by people with eating disorders. In anticipation of the release of alli (the brand of orlistat now available over the counter), researchers expressed concerns regarding the potential for alli to be abused by people with eating disorders. Their concerns are based on documentation of adult and adolescent eating disorder patients frequently abusing supplements sold for weight loss, as well as the possibility that alli’s FDA approval would make it more appealing than other products sold for weight loss ³³.

What is healthy weight loss ?

It’s natural for anyone trying to lose weight to want to lose it very quickly. But evidence shows that people who lose weight gradually and steadily (about 1 to 2 pounds per week) are more successful at keeping weight off. Healthy weight loss isn’t just about a “diet” or “program”. It’s about an ongoing lifestyle that includes long-term changes in daily eating and exercise habits. For a free copy of Maintaining a Healthy Weight on the Go go here ³⁴.

• To lose weight, you must use up more calories than you take in. Since one pound equals 3,500 calories, you need to reduce your caloric intake by 500—1000 calories per day to lose about 1 to 2 pounds per week ³⁵.
• Once you’ve achieved a healthy weight, by relying on healthful eating and physical activity most days of the week (about 60—90 minutes, moderate intensity), you are more likely to be successful at keeping the weight off over the long term.

Losing weight is not easy, and it takes commitment ³⁴.

The good news is that no matter what your weight loss goal is, even a modest weight loss, such as 5 to 10 percent of your total body weight, is likely to produce health benefits, such as improvements in blood pressure, blood cholesterol, and blood sugars ³⁶.

For example, if you weigh 200 pounds, a 5 percent weight loss equals 10 pounds, bringing your weight down to 190 pounds. While this weight may still be in the “overweight” or “obese” range, this modest weight loss can decrease your risk factors for chronic diseases related to obesity.

So even if the overall goal seems large, see it as a journey rather than just a final destination. You’ll learn new eating and physical activity habits that will help you live a healthier lifestyle. These habits may help you maintain your weight loss over time.

Health care providers use your Body Mass Index (BMI), to measure of your weight in relation to your height, to define overweight and obesity and is universally expressed in units of kg/m², resulting from mass in kilograms and height in meters. People who have a BMI between 25 and 30 kg/m² are considered overweight. Obesity is defined as having a BMI of 30 kg/m² or greater. BMI is considered an important measure for understanding population trends. For individuals, it is one of many factors that should be considered in evaluating healthy weight, along with waist size, body fat composition, waist circumference, blood pressure, cholesterol level and blood sugar.

To calculate your body mass index, you divide your body weight in kilograms by your height in meter squared (commonly expressed as kg/m²), see the body mass index formula below.

To find out about your body mass index (BMI), you can use a FREE online BMI calculators from the Centers for Disease Control and Prevention (CDC) :

• Adults (BMI Calculator Adults. https://www.cdc.gov/healthyweight/assessing/bmi/adult_BMI/english_bmi_calculator/bmi_calculator.html)

For children and adolescents (younger than 20 years of age), overweight and obesity are based on the Centers for Disease Control and Prevention’s (CDC’s) BMI-for-age growth charts, which are available at Centers for Disease Control and Prevention (CDC Clinical Growth Charts https://www.cdc.gov/growthcharts/clinical_charts.htm).

The CDC has a BMI percentile calculator for children and teens at ³⁷.

• Children (BMI Calculator Children. https://www.cdc.gov/healthyweight/bmi/calculator.html)

Body Mass Index for Men and Women Adults

The body mass index is an attempt to quantify the amount of tissue mass (muscle, fat, and bone) in an individual, and then categorize that person as underweight, normal weight, overweight, or obese based on that value. Commonly accepted body mass index ranges are:

A) Underweight: under 18.5 kg/m²,

B) Normal weight: 18.5 to 25 kg/m²,

C) Overweight: 25 to 30 kg/m²,

D) Obese: over 30 to 39.9 kg/m².

E) Severely Obese: over 40 kg/m².

Prescription Weight Loss Pills

Weight-loss medicines, weight loss pills or prescription diet pills approved by the Food and Drug Administration (FDA) might be an option for some people.

If you’re not successful at losing 1 pound a week after 6 months of using lifestyle changes, medicines may help. You should only use medicines as part of a program that includes diet, physical activity, and behavioral changes.

Weight-loss medicines might be suitable for adults who are obese (a BMI of 30 or greater). People who have BMIs of 27 or greater, and who are at risk for heart disease and other health conditions like type 2 diabetes or high blood pressure, also may benefit from weight-loss medicines. You’ll still need to focus on diet and exercise while taking these drugs, and they’re not for everyone.

Only orlistat, lorcaserin (Belviq) and phentermine/topiramate (Qsymia) are FDA-approved for long-term use; the others are approved only for short-term use (usually considered ≤12 weeks).

Table 1. Drugs with an FDA-approved indication for obesity

Generic Name	Trade Name(s)	Mechanism of action	Dosage	Whole-sale price per mo.*	Mean weight change relative to placebo at 1y, kg**	Interactions	Contraindications&	Common Adverse Events&	Cautions and Warnings&
Phenterminea	Adipex-P, Fastin, Oby-Cap, lonamin, Others	Noradrenergic causing appetite suppression	15– 37.5mg/d	$6– $45	Not Available	Guanethidine, CNS stimulants, alcohol, tricyclic antidepressants; requirements for insulin or oral hypoglycemic medications may be altered	Pregnancy or nursing, advanced cardiovascular disease, uncontrolled hypertension, hyperthyroidism, glaucoma, agitated states, history of drug abuse, MAOIs	Insomnia, elevation in heart rate, dry mouth, taste alterations, dizziness, tremors, headache, diarrhea, constipation, vomiting, gastro- intestinal distress, anxiety, and restlessness.	Do not increase beyond recommended dose if tolerance to the anorexiant effect develops. Caution prescribing to patients with even mild hypertension. Caution for patients using alcohol or other CNS active drugs or engaging in hazardous activity.
Diethylpropiona	Tenuate, Tenuate Dospan, Tepanil	Noradrenergic causing appetite suppression	25mg 3 times/d or 75mg sustained- release/d	$47– $120	Not Available	Same as phentermine	Same as phentermine	Same as phentermine	Same as phentermine
Phendimetrazineb	Bontril	Noradrenergic	17.5–70mg 2–3 times/d or 105mg sustained- release/d	$6– $20	Not Available	Same as phentermine	Same as phentermine	Same as phentermine	Same as phentermine
Benzphetamineb	Didrex	Noradrenergic causing appetite suppression	25–50mg 1–3 times/d	$20– $50	Not Available	Same as phentermine	Same as phentermine	Same as phentermine	Same as phentermine
Orlistatc	Xenical, Alli	Lipase inhibitor causing excretion of ~30% of ingested triglycerides in stool	60 or 120mg 3 times/d within 1 hr of a fat- containing meals, plus a daily multi- vitamin	For 60mg TID: $45 For 120mg TID: $207	For 60mg TID:−2.5 kg (−1.5 to −3.5) For 120mg TID: −3.4 kg (−3.2 to −3.6)	Decreased drug concentrations of cyclosporine and levothyroxine. Doses should be temporally separated from orlistat. Fat soluble vitamin absorption is decreased by orlistat	Pregnancy, chronic malabsorption syndromes, cholestasis	Oily Spotting, Flatus with Discharge, Fecal Urgency, Fatty/Oily Stool, Increased Defecation, Fecal Incontinence	Use with caution in those at risk for renal insufficiency, since treatment may increase urinary oxalate. Cholelithiasis and, rarely, severe liver injury including hepatocellular necrosis and acute hepatic failure leading to death, have been reported
Lorcaserina	Belviq	Highly selective serotonergic 5-HT2C receptor agonist causing appetite suppression	10mg two times/d	$240	−3.2 kg (−2.7 to −3.8)	Triptans, MAOIs including linezolid, SSRIs, SNRIs, dextro- methorphan, tricyclic antidepressants, bupropion, lithium, tramadol, tryptophan, and St. John’s Wort	Pregnancy	Headache, dizziness, fatigue, nausea, dry mouth, cough, and constipation, and back pain, cough and hypoglycemia in patients with type 2 diabetes.	Risk for Serotonin Syndrome or Neuroleptic Malignant Syndrome-like Reactions. Evaluate patients for signs or symptoms of valvular heart disease. Euphoria, hallucination, and dissociation have been seen with supra- therapeutic doses. Use with caution in men at risk for priapism
Phentermine / Topiramate-ERa	Qsymia	Noradrenergic + GABA- receptor activator, kainite/AMPA glutamate receptor inhibitor causing appetite suppression	3.75/23mg /d for 2 weeks, then 7.5/46mg/ d, escalating to a maximum of 15/92mg/d	$140 – $195	For 7.5/46mgd: −6.7 kg (−5.9 to −7.5) For 15/92mg/d −8.9 kg (−8.3 to −9.4)	Oral contraceptives, alcohol and other CNS depressants, non-potassium- sparing diuretics	Pregnancy, Glaucoma, Hyperthyroidism, MAOIs

Abbreviations: MAOI = monoamine oxidase inhibitor, CNS = central nervous system, SSRI = selective serotonin-reuptake inhibitors, SNRI = selective serotonin-norepinephrine reuptake inhibitors.

*Reference prices found on March 8, 2013.
**Weight change relative to placebo (95 percentile confidence interval) using intent-to-treat analyses for each medication at 1 year. No studies for older noradrenergic agents (phentermine, diethylpropion, phendimetrazine, and benzphetamine) met inclusion criteria for length of treatment, sample size, and attrition.
^a Medications listed on Drug Enforcement Administration Schedule IV are associated with a lower risk of abuse than
^b Medications on Schedule III;
^c Orlistat is a non-Drug Enforcement Administration scheduled drug.
^& Common adverse events for noradrenergic agents include those listed as common in the NIDDK Weight-control Information Network Fact Sheet “Prescription Medications for the Treatment of Obesity”100 as adverse event frequency is not available in the drug package inserts for these agents. For orlistat, lorcaserin, and phentermine/topiramate ER, common adverse events are those listed in the drug package inserts that are reported to occur more frequently than placebo and with more than 5% prevalence.

[Source ³⁸]

1) Orlistat (Xenical)

How it works: Blocks your body from absorbing about a third of the fat you eat. Orlistat is a gastrointestinal lipase inhibitor which, when taken three times a day during or up to 1 hour after meals, leads to the excretion of approximately 30% of ingested fat.

Orlistat is available both in prescription (120mg) and over-the-counter (60mg) strength. Orlistat 120mg is FDA-approved for use in adults and adolescents age 12–16years.

When a doctor prescribes orlistat, it’s called Xenical (Orlistat 120mg). If you get it without a prescription, it’s called Alli, which has half of Xenical’s dose. Alli is the reduced-strength, 60-milligram version of orlistat (Xenical) a 120-milligram prescription drug.

The mean weight reduction attributable to orlistat 120mg three times daily at 12 months is modest: among adults participating in behavioral weight control programs and prescribed a lower fat diet (~30% of calories from fat), orlistat-treated patients lost on average 3.4 kg (~3.1% of initial weight) more than placebo-treated participants. The percentage of orlistat 120mg-treated participants who achieved clinically-meaningful (≥5%) weight loss at 1 year varied from 35–73% and the proportion losing ≥10% varied from 14–41%, with both ≥5% and ≥10% weight loss at 1 year significantly greater for orlistat-treated than for placebo-treated participants. At the end of a second year of treatment when a weight-maintenance diet was prescribed, orlistat 120mg-treated participants had lost approximately 3.3 kg (~3.3% of initial weight) more and orlistat 60mg-treated participants had lost approximately 2.5 kg (~2.5% of initial weight) more than those given placebo.

Because of its weight-loss related and weight-loss independent ³⁹ actions, orlistat 120mg treatment is associated with significant improvements in cardiovascular risk factors including decreases in total- and LDL- cholesterol, fasting glucose, and systolic and diastolic blood pressures after 1 year of treatment ⁴⁰.

Data from the XENDOS trial ⁴¹ of 3,305 patients treated for up to 4 years (attrition at 4 years: 48% for orlistat-treated and 66% for placebo-treated) found, in an intention-to-treat approach, that orlistat use decreased body weight over 4 years by 2.7 kg (approximately 2.4% of initial body weight) more than placebo and significantly decreased risk for developing type 2 diabetes from 9.0% with placebo to 6.2% with orlistat. Because orlistat leads to obligate increases in undigested stool triglycerides, it may cause considerable gastrointestinal adverse effects that may be decreased by co-administration of fiber-containing supplements ⁴².

Side effects include abdominal cramping, passing gas, leaking oily stool, having more bowel movements, and not being able to control bowel movements.

These side effects are generally mild and temporary. But they may get worse if you eat high-fat foods.

These adverse effects may cause patients who do not reduce their fat intake to discontinue therapy. Indeed, despite being FDA-approved in 1999 for indefinite treatment of obesity, among those prescribed orlistat 120mg clinically, fewer than 10% take it for at least 1y and <2% of patients use the medication for 2 years ⁴³.

Rare cases of severe liver injury have been reported in people taking orlistat, but it’s not certain that the drug caused those problems.

What else you should know: You should be on a low-fat diet (less than 30% of your daily calories from fat) before taking orlistat.

Also, take a multivitamin at least 2 hours before or after taking orlistat, because the drug temporarily makes it harder for your body to absorb vitamins A, vitamin D, vitamin E, and vitamin K.

Orlistat is the only drug of its kind that’s approved in the U.S. All other prescription weight loss drugs curb your appetite, including the following.

2) Belviq (Lorcaserin Hydrochloride)

How it works: Curbs your appetite. Lorcaserin is a selective serotonin 2C (5HT_2c) receptor agonist that was anticipated to recapitulate the weight loss effects of fenfluramine without its adverse cardiac effects ⁴⁴. Lorcaserin 10mg twice daily was FDA-approved in 2012 on the basis of two large randomized, placebo-controlled trials in nondiabetic patients (BLOOM n=3182, 50% attrition) ⁴⁵; BLOSSOM n=4004, 45% attrition) ⁴⁶, along with a third, smaller trial in adults with type 2 diabetes (BLOOM-DM n=603, 34% attrition) ⁴⁷. In these trials, participants received low-intensity nutritional and exercise counseling. Lorcaserin decreased body weight modestly, by about 3.2 kg (~3.2% of initial body weight) more than placebo ⁴⁸. However, significantly more patients treated with lorcaserin 10mg twice daily than placebo lost ≥5% (BLOOM: 47 vs. 20%, BLOSSOM: 47 vs. 25%, BLOOM-DM: 37 vs. 16%) or ≥10% (BLOOM: 23 vs. 8%, BLOSSOM: 23 vs. 10%, BLOOM-DM: 16 vs. 4%) of their initial weight. Reduction in body weight below baseline in the one study ⁴⁵ with data from participants who took lorcaserin for 2 years had average weight loss of 5.6 kg, versus 2.4 kg among placebo-treated participants. Blood pressure, total cholesterol, LDL”bad” cholesterol, and triglycerides also decreased significantly more in lorcaserin-treated participants ⁴⁹. Among patients with diabetes, lorcaserin treatment led to lower body weight and improved glycated hemoglobin concentrations.30 Adverse effects (Table 1) include headache, nausea, fatigue, and dizziness ⁴⁹. Although neither incidence of valvulopathy nor hypertension was statistically greater during lorcaserin than placebo treatment, both were numerically somewhat more prevalent and the FDA has requested that a post-approval trial to assess the long-term cardiovascular effects of lorcaserin be conducted ⁵⁰.

Side effects: The most common side effects in people who don’t have diabetes are headache, dizziness, nausea, fatigue, dry mouth, and constipation.

The most common side effects in those who have diabetes are low blood sugar (hypoglycemia), headache, back pain, cough, and fatigue.

People taking some depression medications with Belviq need to be monitored very closely for a rare but serious reaction that includes fever and confusion.

Women who are pregnant or planning to get pregnant shouldn’t take Belviq.

What else you should know: If you don’t lose 5% of your weight after 12 weeks of taking Belviq, you should stop taking it, because it’s unlikely to work for you, the FDA says.

3) Contrave

How it works: Contrave is a combination of two FDA-approved drugs, naltrexone and bupropion, in an extended-release formula. Naltrexone is approved to treat alcohol and opioid dependence. Bupropion is approved to treat depression, seasonal affective disorder, and help people stop smoking.

Side effects: The most common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea. Contrave has a boxed warning about the increased risk of suicidal thoughts and behaviors associated with bupropion. The warning also notes that serious neuropsychiatric issues linked to bupropion have been reported. Contrave can cause seizures and must not be used in patients who have seizure disorders. The drug can also increase blood pressure and heart rate.

What else you should know: If you don’t lose 5% of your weight after 12 weeks of taking Contrave, you should stop taking it, because it’s unlikely to work for you, the FDA says.

4) Saxenda

How it works: Saxenda is a higher dose of the type 2 diabetes drug Victoza. It mimics an intestinal hormone that tells the brain your stomach is full.

Side effects: Nausea, vomiting, diarrhea, constipation, low blood pressure, and increased appetite. Serious side effects can include raised heart rate, pancreatitis, gallbladder disease, kidney problems, and suicidal thoughts.

What else you should know: If you don’t lose 4% of your weight after 16 weeks of taking Saxenda, you should stop taking it, because it’s unlikely to work for you, the FDA says.

5) Phentermine

Your doctor may prescribe this under the names Adipex or Suprenza.

How it works: Curbs your appetite.

Phentermine is by far the most widely prescribed obesity medication in the US, with 25.3 million prescriptions dispensed to an estimated 6.2 million users between 2008–2011 ⁴³. Phentermine originally approved indication was obesity; and the drug was used on-label until 1977 when it, along with all other drugs approved for treating obesity, were approved a second time after an amendment to the Food Drug and Cosmetic Act required that the FDA approve new drugs based on efficacy as well as safety. There was protracted opposition to re-approval from those who maintained the sympathomimetic obesity drugs that had dangerous addiction potential. No evidence of addiction had appeared during 18 years of increasingly frequent use, but the FDA re-approved them all, having silenced the opposition by announcing the drugs would be approved for short-term use only ⁵¹. The FDA has jurisdiction over pharmaceutical companies but cannot regulate medical practice, jurisdiction over which resides in the individual US states. US physicians treating obesity, well aware of these statuary boundaries, continued to use phentermine and the other sympathomimetic amine anorectic drugs off-label long-term. Surveys of prescribing practices among physicians treating obesity have confirmed that a majority of these physicians continue to prescribe the sympathomimetics off-label in this manner ⁵².

A meta-analysis of 6 studies ranging from 2 to 24 weeks ⁵³ found that patients using 15–30mg/day phentermine had a mean additional weight loss relative to placebo of 3.6 kg, with mean total weight loss of 6.3 kg. The longest published placebo-controlled trial of phentermine ⁵⁴ lasted 36 weeks in 108 obese women treated with phentermine 30mg/day either continuously or intermittently (alternating months) and found similar weight loss in the continuous (12.2 kg) and intermittent (13.0 kg) arms vs. 4.8 kg with placebo. However, attrition was 41%, and data were presented only for completers, which is likely to overstate efficacy ⁵⁴. Among completers, transient symptoms of central nervous system stimulation such as insomnia, irritability, and anxiety did not differ between those receiving continuous (24%) vs. intermittent (27%) therapy, compared with 8% for those taking placebo. Several short-term placebo-controlled studies of phentermine have shown elevations in pulse or smaller decreases in pulse and/or blood pressure than would be expected given the degree of weight loss ⁵⁵.

Approved for long-term use ? No. It’s approved for short-term use (a few weeks) only.

Side effects can be serious, such as raising your blood pressure or causing heart palpitations, restlessness, dizziness, tremor, insomnia, shortness of breath, chest pain, and trouble doing activities you’ve been able to do.

Phentermine may make you drowsy, hampering your ability to drive or operate machinery. As with some other appetite suppressants, there’s a risk of becoming dependent upon the drug.

Less serious side effects include dry mouth, unpleasant taste, diarrhea, constipation, and vomiting.

Don’t take it late in the evening, as it may cause insomnia.

If you take insulin for diabetes, let your doctor know before you take phentermine, as you may need to adjust your insulin dose.

You should not take phentermine if you have a history of heart disease, stroke, congestive heart failure, or uncontrolled high blood pressure. You also shouldn’t take it if you have glaucoma, hyperthyroidism, or a history of drug abuse, or if you are pregnant or nursing.

What else you should know: Phentermine is an amphetamine. Because of the risk of addiction or abuse, such stimulant drugs are “controlled substances,” which means they need a special type of prescription.

Although there are no published data on the frequency of use, phentermine is occasionally prescribed for patients with label contraindications. Coronary artery disease, stroke, arrhythmias, congestive heart failure, and uncontrolled hypertension are listed specifically. In the absence of controlled data supporting these contraindications, there is no unambiguous evidence that suggests these conditions are absolute contraindications. However, US obesity medicine specialists, based on the known mechanism of action of phentermine, and the pathophysiology of the illness, would consider congestive heart failure, uncontrolled hypertension, untreated clinically significant arrhythmias, and severe advanced coronary artery disease to be absolute contraindications ⁵⁶. However, in cases of less severe coronary artery disease, medically treated arrhythmias and patients who have past history of stroke, some US obesity medicine specialists would weigh the benefits of weight loss in obese, overweight and overfat subjects after a thorough assessment, that would likely include consultation with the patient’s cardiologist and/or medical specialist ⁵⁶. This viewpoint is supported by reduced mortality observed in the Sibutramine Cardiovascular Outcomes (SCOUT) trial for patients with cardiovascular disease who had moderate weight loss ⁵⁷. The expectation is that the same will be discovered with cardiovascular outcome trials that the FDA has mandated for the newer obesity drugs since weight loss in overweight and obese patients induces improvement in cardiac dysfunction common in such patients ⁵⁸.

Other contraindications include hyperthyroidism, glaucoma and history of drug abuse ⁵⁶. Most physicians would likely agree that phentermine not be used until hyperthyroidism has been treated but most would also agree a history of successful treatment of hyperthyroidism is not a contraindication. As with other medications that have anticholinergic side effects, phentermine is contraindicated in patients with narrow-angle glaucoma. However, it is not contraindicated in patients with open-angle glaucoma.

Phentermine use in clinical practice has not been associated with phentermine cravings, withdrawal, or excessive use leading to psychological or physical impairment. Although there is a widespread presumption that phentermine abuse is common, actual phentermine abuse is not common and appears limited to the use of the drug as a stimulant among people trying to stay awake and those trying to boost their energy level. Phentermine is longer acting than caffeine and does not have the adverse gastrointestinal effects of high doses of caffeine, so some students studying for exams and some long-haul truck drivers use it to stay awake and alert. Evidently, some patients with stimulant use disorder who use cocaine, methamphetamine or other strong stimulants add phentermine to a drug cocktail in an attempt to heighten the stimulant effects, but no data have been published on the frequency of this practice. A telephone survey of 50 addiction treatment centers in the USA found only 2 instances of patients using such cocktails among several thousand admissions, suggesting the addition of phentermine to such cocktails is uncommon ⁵⁹. Stimulant use disorder due to phentermine alone as the favored drug has not been described, and no such entity is included in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) ⁶⁰. Clinically significant psychiatric distress similar to that described in the DSM-5 in discussing stimulant use disorders has never been observed in overweight or obese patients treated with phentermine. A phentermine withdrawal syndrome has never been observed or described. Patients with either overt attention deficit or some of its symptoms typically “like” phentermine because they function better when taking it. Patients who have difficulty staying in control of eating also “like” phentermine because they have less cravings and enjoy better control of their eating behaviors. Patients with symptoms of attention deficit are quite common among the overweight and obese. For these reasons, “liking” phentermine should not be interpreted as an indication phentermine has high abuse potential. Phentermine treatment enhances control of impulsive behavior and control of other harmful eating behaviors; these are goals of behavioral treatment in obese patients.

It may be reasonable to prescribe phentermine for subjects who have a history of recovery from drug abuse. The author has found this safe in carefully selected patients provided their recovery is genuine, recovery has endured for at least several years and phentermine does not induce phentermine cravings or desire for their former drugs of abuse.

The label also lists contraindications that are absolute and seldom ignored, and these include recent monoamine oxidase inhibitor use, agitated states, pregnancy, nursing mothers and known hypersensitivity or idiosyncratic reactions to sympathetic amines.

Phentermine label warnings

Some consider prescribing phentermine despite specific label warnings to be an off-label use. It is recommended that the label warnings be included in an informed consent, and that any concern of the patient be thoroughly discussed and the discussion documented. The rationale for decisions to prescribe phentermine contrary to a warning would best be explicitly documented in the patient record.

Co-administration with other weight-loss drugs

US physicians view this warning as an anachronism since the FDA has approved the two combination drugs phentermine/topiramate and bupropion/naltrexone ⁵⁶. The warning against combining weight-loss medicines appeared in the phentermine label in 2000 after 1997 reports of valvulopathy induced by the combination of phentermine and fenfluramine, and both dexfenfluramine and fenfluramine were taken off-market. Surveys of US physicians treating obesity have revealed these physicians frequently combined the various antiobesity drugs with other drugs approved for obesity and with a variety of other drugs that have an effect on weight loss. For example, these physicians combined phentermine and topiramate long before the FDA approved a fixed dose combination (Qsymia) in 2012 ⁵⁶. Other combinations in use are discussed.

Primary pulmonary hypertension

Primary pulmonary hypertension has not been associated with phentermine monotherapy. As discussed in a previous communication, isolated reports of primary pulmonary hypertension occurring in patients who have taken phentermine have relied on theoretical but unproven adverse effects and ignored the underlying incidence of idiopathic pulmonary hypertension ⁶¹.

Valvular heart disease

This warning first appeared in the label in 2000 after valvulopathy was discovered in patients taking phentermine and fenfluramine in 1997 and before publication of a report suggesting that fenfluramine, but not phentermine, activated cardiac 5HT2B serotonin receptors that then induced valvulopathy ⁶². Although the label states “… there have been rare cases of valvular heart disease in patients who reportedly have taken phentermine alone.”

Tolerance

Tolerance refers to a reduced response to a drug after repeated use. Tolerance is a normal physiologic process that occurs with substances of abuse but also with some medicines (e.g., diphenhydramine). Tachyphylaxis refers to very rapid development of tolerance.

Hazardous task ability

Labels for most drugs that work in the central nervous system include this warning. There is no specific evidence that phentermine degrades mental or physical performance. Generally, stimulants will enhance rather than degrade mental and physical performance until extremely high doses are used. The Federal Aviation Administration (FAA) has not accepted phentermine for pilots ⁶¹. The only antiobesity drug acceptable to the FAA is orlistat ⁶¹.

Risk of abuse and addiction

The Diagnostic and Statistical Manual of Mental Disorders: DSM-5 ⁶⁰ does not have criteria for “addiction” but instead sets forth criteria for diagnosing stimulant-related disorders and discusses “stimulant use disorder” and “stimulant withdrawal” with amphetamine and cocaine as prototypical stimulants. Phentermine is not specifically mentioned in the DSM-5. Stimulant use disorder is defined as a pattern of repeated use leading to clinically significant impairment or distress as manifested by two or more of a list of 11 symptoms, including intense cravings for the substance leading to self-destructive social and job or profession-related behaviors. In phentermine post-marketing studies, we found that long-term phentermine use, even at doses higher than 37.5 mg/day, did not induce phentermine cravings, and that abrupt cessation of long-term phentermine did not induce a stimulant withdrawal syndrome ⁶³.

Assessment of drug “liking” is currently used as a measure of addiction potential ⁶⁴. Phentermine has been used in studies as an example of a liked drug ⁶⁵. However, patients taking phentermine often “like” the drug for a variety of valid reasons but do not have other signs or symptoms of addiction or physical dependence. Some like phentermine because they have lost weight taking it and enjoy a better quality of life. Many patients in medical weight management programs have adult attention deficit or at least some symptoms of attention deficit, and many are not taking specific attention medicines. These patients typically are less scattered, can focus better and are more productive when taking phentermine and, realizing this, “like” taking the drug. Discussions of drug liking of phentermine as a sign of addiction typically fail to consider the prevalence of attention deficit in the obese population as a reason for drug liking. Nor do such discussions differentiate between hedonic drug liking versus drug liking because of medical benefits.

Use with alcohol

There is an extensive literature on the effects of ethanol and a wide variety of stimulants in animals and humans. However, there are no specific reports on the effects of combining phentermine and ethanol in humans.

Hypertension

Phentermine-induced increases in blood pressure are often mentioned in both the medical and general literature, but few instances have been recorded ⁶⁶. US obesity medicine practitioners typically do not prescribe phentermine with poorly controlled hypertension until it is under control, but they do prescribe it in the presence of controlled hypertension, then monitor the patient’s blood pressure closely, discontinuing phentermine if blood pressure rises ⁶¹.

6) Diethylpropion

Diethylpropion has a similar adverse-effect and weight loss profile to phentermine, but is much less frequently prescribed, with approximately 1 million prescriptions dispensed between 2008–2011 ⁴³. A meta-analysis of 9 small studies ranging from 6–52 weeks ⁶⁷ found that patients using diethylpropion 75mg/day had a mean additional weight loss relative to placebo of 3.0 kg, with a mean total weight loss of 6.5 kg.

7) Phendimetrazine

Phendimetrazine, despite the paucity of randomized controlled trials ⁶⁷ is prescribed three times more frequently than diethylpropion for obesity treatment, with more than 3 million phendimetrazine prescriptions estimated to have been filled between 2008–2011 ⁴³. In the completer’s analyses from two small 12-week trials ⁶⁸, phendimetrazine appears to have similar weight loss to other noradrenergic drugs.

8) Benzphetamine

Benzphetamine is less commonly prescribed for obesity treatment than the other noradrenergic drugs ⁶⁷ and there are few data from controlled trials evaluating its safety or efficacy ⁶⁷.

Common adverse effects of noradrenergic drugs are shown in Table 1. Because these medications were approved prior to the requirements for long-term trials with adequate power to ascertain clinical endpoints, an adverse effect of noradrenergic obesity drugs on cardiovascular disease events cannot be excluded, and is of concern given their known effect on heart rate and blood pressure.

9) Qsymia

How it works: Curbs your appetite. Qsymia combines phentermine with the seizure/migraine drug topiramate. Topiramate causes weight loss in several ways, including helping you feel full, making foods taste less appealing, and burning more calories.

Phentermine/topiramate-Extended Release (ER) is the first FDA-approved combination drug for obesity, combining low-dose phentermine with a non-standard dose of the antiepileptic medication topiramate-Extended Release (ER).

Phentermine/topiramate-ER, is administered as a once-daily capsule in 4 fixed-dose combinations: 3.75mg phentermine/23mg topiramate (starting dose); 7.5mg phentermine/46mg topiramate (recommended dose); 11.25mg phentermine/69mg topiramate (titration dose); and 15mg phentermine/92mg topiramate (top dose). Dosage is increased over 14 days to 7.5mg phentermine/46mg topiramate, with additional titration to the top dose if weight loss is inadequate ⁶⁹.

Phentermine/topiramate-ER was recommended for approval based largely on 2 one-year Phase 3 clinical trials (EQUIP, n=1267) ⁷⁰; CONQUER, n=2487) ⁷¹. All groups received a low-intensity lifestyle program. All underwent dose titration over 4 weeks to assigned dose followed by 52 weeks on drug or placebo. EQUIP ⁷⁰; CONQUER, n=2487) ⁷² randomized a higher-risk sample of adults with BMI 27–45 kg/m² and ≥2 obesity-associated comorbid conditions, to placebo or phentermine/topiramate-ER. 31% of participants withdrew. One year weight loss was 8.1 kg (7.8%) with the recommended dose and 10.2 kg (9.8%) with the top dose, vs. 1.4 kg (1.2%) with placebo. In addition, 62% (recommended dose) and 70% (top dose) lost ≥5% of initial weight vs. 21% for placebo, with 37%, 48%, and 7% respectively losing ≥10% of initial weight. Many cardiovascular disease risk factors improved with active drug treatment at recommended- or top-dose ⁷³. SEQUEL ⁷⁴ an extension to CONQUER, followed 78% of CONQUER participants at sites selected for high enrollment and retention and who had completed the initial 56-week trial for a total of 108 weeks. 84% completed their second year of treatment with sustained weight loss of 9.3% and 10.5% at the recommended and top doses, respectively, vs. 1.8% for placebo, and continued differences in many cardiovascular disease risk factors. In addition, there was a significantly lower incidence of progression to type 2 diabetes in the top-dose group (0.9%) vs. placebo (3.7%).

An area of considerable concern, given that most users of obesity medications are women of reproductive age, is the potential for oral clefts in the offspring of women who become pregnant while taking topiramate ⁷⁵. A risk evaluation and mitigation strategy was developed to minimize the likelihood of pregnancy in women with reproductive potential that includes provider training, dispensing only via certified pharmacies, and supplying patient information regarding risks and the necessity of using effective contraception ⁷⁶. Women with childbearing potential should have a negative pregnancy test prior to starting phentermine/topiramate-ER and monthly thereafter ⁷⁶. A small increase in resting heart rate has been observed in the clinical trials of phentermine/topiramate-ER at higher doses, with more patients on top-dose (56.1%) than placebo (42.1%) having increases of more than 10 beats per minute, leading to some concerns regarding its potential long-term effect on cardiovascular disease events. Phentermine/topiramate-ER was approved with a requirement for a post-marketing trial of to assess long-term cardiovascular safety ⁵⁰. The labeling recommends against prescription in patients with recent or unstable cardiac or cerebrovascular disease, and suggests regular monitoring of resting heart rate ⁶⁹.

Side effects: The most common side effects are tingling hands and feet, dizziness, altered sense of taste, insomnia, constipation, and dry mouth.

Serious side effects include certain birth defects (cleft lip and cleft palate), faster heart rate, suicidal thoughts or actions, and eye problems that could lead to permanent vision loss if not treated.

Women who might become pregnant should get a pregnancy test before taking Qsymia, and should use birth control and get monthly pregnancy tests while on the drug.

You also shouldn’t take Qsymia if you have glaucoma, hyperthyroidism, heart disease, or stroke. Get regular checks of your heart when starting the drug or increasing the dose.

What else you should know: If you don’t lose 3% of your weight after 12 weeks on Qsymia, the FDA recommends that you stop taking it or that your doctor increase your dose for the next 12 weeks — and if that doesn’t work, you should gradually stop taking it.

Bottom Line

• Most dietary supplements marketed for rapid weight loss, such as acai and hoodia, don’t work for keeping weight off in the long term, and some are dangerous. For example, ephedra, which was used in weight loss supplements, was banned because of unreasonable risk of injury or illness.
• Researchers have studied the weight loss potential of a variety of dietary supplements, including omega-3s and fish oil; chitosan, a dietary fiber from shellfish; green tea extracts; Chinese herbs; and bitter orange (Citrus aurantium) extract. None have been shown to be effective for weight loss, and each of these has side effects.
• There’s some emerging evidence suggesting that some mind and body approaches, such as yoga and meditation, particularly mindful eating, may be useful as complements to other weight-loss interventions.

Safety

• The U.S. Food and Drug Administration (FDA) banned the sale of dietary supplements containing ephedra, which was marketed for weight loss, because of serious health risks, such as cardiovascular complications and even risk of death. Ephedra is also called ma huang.
• Many ephedra-free supplements are now being sold, but side effects of some of their ingredients are similar to the banned products. Some ephedra-free supplements also have a lot of caffeine or herbs, such as guarana, that contain caffeine. The products can cause increased heart rate and abnormal heart rhythms.
• Many dietary supplements marketed for weight-loss (including ones sold as “fat burners” or appetite suppressants) have not been tested for safety.
• What’s on the label may not be what’s in the bottle. Analyses of dietary supplements, including herbal supplements, sometimes find differences between labeled and actual ingredients. Also, the FDA has found weight-loss products tainted with prescription drug ingredients.
• Dietary supplements for weight loss are sometimes misused by people with eating disorders, such as anorexia nervosa or bulimia nervosa, to lose weight or induce vomiting.
• If you’re considering a dietary supplement for weight loss, remember that “natural” does not necessarily mean “safe.”
• Mind and body practices, such as meditation and yoga, are generally considered safe for healthy people when practiced appropriately under the guidance of a well-trained instructor. If you have any underlying health conditions, talk to your health care provider about any complementary approach you may be interested in using.

References

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28. Cohen P, Bloszies C, Yee C, Gerona R. An amphetamine isomer whose efficacy and safety in humans has never been studied, β-methylphenylethylamine (BMPEA), is found in multiple dietary supplements. Drug Testing and Analysis. 2015;8(3-4), 328-333.
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41. Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27(1):155–161 http://care.diabetesjournals.org/content/27/1/155.long
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43. Use of prescription antiobesity drugs in the United States. Hampp C, Kang EM, Borders-Hemphill V. Pharmacotherapy. 2013 Dec; 33(12):1299-307. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740913/
44. Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med. 1997;337(9):581–588.
45. Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363(3):245–256.
46. Fidler MC, Sanchez M, Raether B, et al. A One-Year Randomized Trial of Lorcaserin for Weight Loss in Obese and Overweight Adults: The BLOSSOM Trial. J Clin Endocrinol Metab. 2011
47. O’Neil PM, Smith SR, Weissman NJ, et al. Randomized Placebo-Controlled Clinical Trial of Lorcaserin for Weight Loss in Type 2 Diabetes Mellitus: The BLOOM-DM Study. Obesity (Silver Spring) 2012;20(7):1426–1436.
48. Chan EW, He Y, Chui CS, Wong AY, Lau WC, Wong IC. Efficacy and safety of lorcaserin in obese adults: a meta-analysis of 1-year randomized controlled trials (RCTs) and narrative review on short-term RCTs. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2013;14(5):383–392.
49. BELVIQ (lorcaserin hydrochloride) tablets, for oral use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022529lbl.pdf
50. Colman E, Golden J, Roberts M, Egan A, Weaver J, Rosebraugh C. The FDA’s assessment of two drugs for chronic weight management. The New England journal of medicine. 2012;367(17):1577–1579.
51. Colman E. Anorectics on trial: a half century of federal regulation of prescription appetite suppressants. Ann Intern Med. 2005;143(5):380–385
52. Schmidt SL, Bryman D, Greenway FL, Hendricks EJ. How physician obesity medicine specialists treated obesity before 2012 new drug approvals. Obes Surg. 2015;25(1):186–190. https://www.ncbi.nlm.nih.gov/pubmed/25344465
53. Haddock CK, Poston WS, Dill PL, Foreyt JP, Ericsson M. Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials. Int J Obes Relat Metab Disord. 2002;26(2):262–273
54. Munro JF, MacCuish AC, Wilson EM, Duncan LJ. Comparison of continuous and intermittent anorectic therapy in obesity. Br Med J. 1968;1(5588):352–354. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1984840/pdf/brmedj02070-0040.pdf
55. Ryan DH, Bray GA. Pharmacologic treatment options for obesity: what is old is new again. Curr Hypertens Rep. 2013;15(3):182–189.
56. Hendricks EJ. Off-label drugs for weight management. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2017;10:223-234. doi:10.2147/DMSO.S95299. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473499/
57. Caterson ID, Finer N, Coutinho W, et al. Maintained intentional weight loss reduces cardiovascular outcomes: results from the Sibutramine Cardiovascular OUTcomes (SCOUT) trial. Diabetes Obes Metab. 2012;14(6):523–530.
58. de las Fuentes L, Waggoner AD, Mohammed BS, et al. Effect of moderate diet-induced weight loss and weight regain on cardiovascular structure and function. J Am Coll Cardiol. 2009;54(25):2376–2381.
59. Bryman D, Hendricks EJ, Schmidt SL. Incidence of addiction and abuse due to phentermine, diethylpropion, and phendimetrazine in the United States. Telephone Survey of Emergency Rooms and Addiction Treatment Centers ed. Unpublished manuscript. 2013
60. American Psychiatric Association, DSM-5 Task Force . Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. American Psychiatric Association: Arlington, VA; 2013.
61. Hendricks EJ, Rothman RB. RE: pulmonary hypertension associated with use of phentermine? Yonsei Med J. 2011;52(5):869–870 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159930/
62. Rothman RB, Baumann MH, Savage JE, et al. Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation. 2000;102(23):2836–2841.
63. Hendricks EJ, Greenway FL. A study of abrupt phentermine cessation in patients in a weight management program. Am J Ther. 2011;18(4):292–299.
64. Berridge KC, Robinson TE. Liking, wanting, and the incentive-sensitization theory of addiction. Am Psychol. 2016;71(8):670–679.
65. Schoedel KA, Addy C, Chakraborty B, et al. Human abuse potential and cognitive effects of taranabant, a cannabinoid 1 receptor inverse agonist: a randomized, double-blind, placebo- and active-controlled, crossover study in recreational polydrug users. J Clin Psychopharmacol. 2012;32(4):492–502.
66. Hendricks EJ, Rothman RB. Phentermine therapy for obesity does not elevate blood pressure. Diabetes Obes Metab. 2011;13(10):963–964. https://www.ncbi.nlm.nih.gov/pubmed/21896124
67. Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials. Haddock CK, Poston WS, Dill PL, Foreyt JP, Ericsson M. Int J Obes Relat Metab Disord. 2002 Feb; 26(2):262-73. https://www.ncbi.nlm.nih.gov/pubmed/11850760/
68. Sustained-action phendimetrazine in obesity. Hadler AJ. J Clin Pharmacol J New Drugs. 1968 Mar-Apr; 8(2):113-7. https://www.ncbi.nlm.nih.gov/pubmed/4871210/
69. Qsymia (phentermine and topiramate extended-release) capsules, for oral use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022580s004lbl.pdf
70. Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP) Obesity (Silver Spring) 2012;20(2):330–342. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270297/
71. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341–1352. https://www.ncbi.nlm.nih.gov/pubmed/21481449
72. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight a randomized adults without diabetes and with BMI ≥35 kg/m² to placebo, phentermine/topiramate-ER 3.75/23mg (starting dose), or 15/92mg (top dose). 40% of participants withdrew. At the top dose, mean 1 year weight loss was 10.9% vs. 1.6% of initial weight for placebo. 67% of patients given the top dose lost ≥5% of initial weight and 47% lost ≥10% of initial weight, compared with 17% and 7%, respectively for placebo. CONQUER ((Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9774):1341–1352. https://www.ncbi.nlm.nih.gov/pubmed/21481449
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74. Garvey WT, Ryan DH, Look M, et al. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr. 2012;95(2):297–308. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260065/
75. Margulis AV, Mitchell AA, Gilboa SM, et al. Use of topiramate in pregnancy and risk of oral clefts. American journal of obstetrics and gynecology. 2012;207(5):405, e401–407. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484193/
76. QSYMIA (phentermine and topiramate extended-release) Capsules. Risk evaluation and mitigation strategy (REMS). https://www.fda.gov/downloads/forindustry/userfees/prescriptiondruguserfee/ucm361075.pdf

Weight Loss Supplements Review

When you want to drop some weight, it’s tempting to look for help anywhere you can. If your thoughts turn to weight loss supplements or herbal remedies, keep in mind that research gives many of them mixed reviews. In some cases, there isn’t a lot of science to back up the claims, and some have health risks. Limited research also makes it difficult to judge the safety of a weight-loss supplement. And a product isn’t necessarily safe simply because it’s natural.

More than two-third of adults and almost one-third of children and adolescents in the United States are overweight or obese ¹, ². Forty-five percent of overweight Americans and 67% of those who are obese are trying to lose weight ³.

Health experts agree that making lifestyle changes—including following a healthy eating pattern, reducing caloric intake, and engaging in physical activity—is the basis for achieving long-term weight loss ⁴, ⁵, ⁶, ⁷. But because making diet and lifestyle changes can be difficult, many people turn to dietary supplements promoted for weight loss in the hope that these products will help them more easily achieve their weight-loss goals.

Use of weight-loss supplements in the United States is fairly common. Approximately 15% of U.S. adults have used a weight-loss dietary supplement at some point in their lives, with more women reporting use (20.6%) than men (9.7%) ⁸. Americans spend about $2 billion a year on weight-loss dietary supplements in pill form (e.g., tablets, capsules, and softgels) and to lose weight is one of the top 20 reasons why people take dietary supplements ⁹.

Dietary supplements promoted for weight loss encompass a wide variety of products and come in a variety of forms, including capsules, tablets, liquids, powders, and bars ¹⁰. Manufacturers market these products with various claims, including that these products reduce macronutrient absorption, appetite, body fat, and weight and increase metabolism and thermogenesis. The average product contains 10 different ingredients, but some contain as many as 96 ¹⁰. Common ingredients include botanicals (herbs and other plant components), dietary fiber, and minerals.

In its report on dietary supplements for weight loss, the U.S. Government Accountability Office concluded that “little is known about whether weight loss supplements are effective, but some supplements have been associated with the potential for physical harm” ¹¹. Many weight-loss supplements are costly, and some of these products’ ingredients can interact or interfere with certain medications. So it is important to consider what is known—and not known—about each ingredient in any dietary supplement before using it.

People who are considering using weight-loss supplements should talk with their health care provider to discuss these products’ potential benefits and risks. This is especially important for those who have medical conditions, including high blood pressure, diabetes, or heart disease. Yet according to a large national survey, less than one-third of U.S. adults who use weight-loss dietary supplements discuss this use with a health care professional.

Regulation of Weight-Loss Dietary Supplements

The U.S. Food and Drug Administration (FDA) regulates dietary supplements promoted for weight loss in accordance with the Dietary Supplement Health and Education Act of 1994. Like other dietary supplements, weight-loss supplements differ from over-the-counter or prescription medications in that the FDA does not classify them as drugs. Unlike drugs, dietary supplements do not require premarket review or approval by the FDA. Supplement manufacturers are responsible for determining that their products are safe and their label claims are truthful and not misleading. However, manufacturers are not required to provide that evidence to the FDA before marketing their products. If the FDA finds a supplement to be unsafe, it may remove the product from the market or ask the manufacturer to voluntarily recall the product. The FDA and the Federal Trade Commission (FTC) may also take regulatory actions against manufacturers that make unsubstantiated weight-loss claims about their products. The FDA does not permit dietary supplements to contain pharmaceutical ingredients, and manufacturers may not promote these products to diagnose, treat, cure, or prevent any disease.

The Dietary Supplement Label

All products labeled as a dietary supplement carry a Supplement Facts panel that lists the contents, amount of active ingredients per serving, and other added ingredients (like fillers, binders, and flavorings). The manufacturer suggests the serving size, but you or your health care provider might decide that a different amount is more appropriate for you.

Common Ingredients in Weight-Loss Dietary Supplements

Weight-loss dietary supplements contain a wide variety of ingredients. Not surprisingly, the amount of scientific information available on these ingredients varies considerably. In some cases, purported benefits are based on limited theoretical data or animal and laboratory studies rather than human clinical trials. In other cases, studies supporting a given ingredient’s use are small, of short duration, and/or of poor quality, limiting the strength of the findings. In almost all cases, additional research is needed to fully understand the safety and/or efficacy of a particular ingredient ³.

Complicating the interpretation of many study results is the fact that most weight-loss dietary supplements contain multiple ingredients, making it difficult to isolate the effects of each ingredient and predict the effects of the combination. Furthermore, dosages and amounts of active components vary widely among weight-loss supplements, and a product’s composition is not always fully described in published studies ¹². Studies may also use different and sometimes inappropriate assessment techniques to measure the effectiveness of a given treatment. All of these factors can make it difficult to compare the results of one study with another.

Table 1 briefly summarizes the findings discussed in more detail in this fact sheet on the safety and efficacy of the most common ingredients of weight-loss dietary supplements. These ingredients are listed and discussed in the table and in the text in alphabetical order. Dosage information is provided when such information is available. However, because ingredients might not be standardized and many products contain proprietary blends of ingredients, the active compounds and their amounts might not be comparable among products ¹³.

 

Table 1: Common Ingredients in Weight-Loss Dietary Supplements* ¹⁴

Ingredient	Proposed Mechanism of Action	Evidence of Efficacy	Evidence of Safety+
Bitter orange (synephrine)	Increases energy expenditure and lipolysis, acts as a mild appetite suppressant	Small clinical trials of poor methodological quality Research findings: Possible effect on resting metabolic rate and energy expenditure; inconclusive effects on weight loss	Some safety concerns reported Reported adverse effects: Chest pain, anxiety, and increased blood pressure and heart rate
Caffeine (as added caffeine or from guarana, kola nut, yerba mate, or other herbs)	Stimulates central nervous system, increases thermogenesis and fat oxidation	Short-term clinical trials of combination products Research findings: Possible modest effect on body weight or decreased weight gain over time	Safety concerns not usually reported at doses less than 400 mg/day for adults, significant safety concerns at higher doses Reported adverse effects: Nervousness, jitteriness, vomiting, and tachycardia
Calcium	Increases lipolysis and fat accumulation, decreases fat absorption	Several large clinical trials Research findings: No effect on body weight, weight loss, or prevention of weight gain based on clinical trials	No safety concerns reported at recommended intakes (1,000–1,200 mg/day for adults) Reported adverse effects: Constipation, kidney stones, and interference with zinc and iron absorption at intakes above 2,000–2,500 mg for adults
Chitosan	Binds dietary fat in the digestive tract	Small clinical trials, mostly of poor methodological quality Research findings: Minimal effect on body weight	Few safety concerns reported, could cause allergic reactions Reported adverse effects: Flatulence, bloating, constipation, indigestion, nausea, and heartburn
Chromium	Increases lean muscle mass; promotes fat loss; and reduces food intake, hunger levels, and fat cravings	Several clinical trials of varying methodological quality Research findings: Minimal effect on body weight and body fat	No safety concerns reported at recommended intakes (25–45 mcg/day for adults) Reported adverse effects: Headache, watery stools, constipation, weakness, vertigo, nausea, vomiting, and urticaria (hives)
Coleus forskohlii (forskolin)	Enhances lipolysis and reduces appetite	Few short-term clinical trials Research findings: No effect on body weight	No safety concerns reported Reported adverse effects: None known
Conjugated linoleic acid	Promotes apoptosis in adipose tissue	Several clinical trials Research findings: Minimal effect on body weight and body fat	Few safety concerns reported Reported adverse effects: Abdominal discomfort and pain, constipation, diarrhea, loose stools, dyspepsia, and (possibly) adverse effects on blood lipid profiles
Ephedra (ma huang, ephedrine)	Stimulates central nervous system, increases thermogenesis, reduces appetite	Several short-term clinical trials of good methodological quality, many of ephedra combined with caffeine Research findings: Modest effect on short-term weight loss	Significant safety concerns reported; banned as a dietary supplement ingredient Reported adverse effects: Anxiety, mood changes, nausea, vomiting, hypertension, palpitation, stroke, seizures, heart attack, and death
Fucoxanthin	Increases energy expenditure and fatty acid oxidation, suppresses adipocyte differentiation and lipid accumulation	Studied only in combination with pomegranate-seed oil in one trial in humans Research findings: Insufficient research to draw firm conclusions	No safety concerns reported but not rigorously studied Reported adverse effects: None known
Garcinia cambogia (hydroxycitric acid)	Inhibits lipogenesis, suppresses food intake	Several short-term clinical trials of varying methodological quality Research findings: Little to no effect on body weight	Few safety concerns reported Reported adverse effects: Headache, nausea, upper respiratory tract symptoms, and gastrointestinal symptoms
Glucomannan	Increases feelings of satiety and fullness, prolongs gastric emptying time	Several clinical trials of varying methodological quality, mostly focused on effects on lipid and blood glucose levels Research findings: Little to no effect on body weight	Significant safety concerns reported with tablet forms, which might cause esophageal obstructions, but few safety concerns with other forms Reported adverse effects: Loose stools, flatulence, diarrhea, constipation, and abdominal discomfort
Green coffee bean extract (Coffea aribica, Coffea canephora, Coffea robusta)	Inhibits fat accumulation, modulates glucose metabolism	Few clinical trials, all of poor methodological quality Research findings: Possible modest effect on body weight	Few safety concerns reported but not rigorously studied; contains caffeine Reported adverse effects: Headache and urinary tract infections
Green tea (Camellia sinensis) and green tea extract	Increases energy expenditure and fat oxidation, reduces lipogenesis and fat absorption	Several clinical trials of good methodological quality on green tea catechins with and without caffeine Research findings: Possible modest effect on body weight	No safety concerns reported when used as a beverage, contains caffeine; some safety concerns reported for green tea extract Reported adverse effects (for green tea extract): Constipation, abdominal discomfort, nausea, increased blood pressure, liver damage
Guar gum	Acts as bulking agent in gut, delays gastric emptying, increases feelings of satiety	Several clinical trials of good methodological quality Research findings: No effect on body weight	Few safety concerns reported with currently available formulations Reported adverse effects: Abdominal pain, flatulence, diarrhea, nausea, and cramps
Hoodia (Hoodia gordonii)	Suppresses appetite, reduces food intake	Very little published research in humans Research findings: No effect on energy intake or body weight based on results from one study	Some safety concerns reported, increases heart rate and blood pressure Reported adverse effects: Headache, dizziness, nausea, and vomiting
Pyruvate	Increases lipolysis and energy expenditure	Few clinical trials of weak methodological quality Research findings: Possible minimal effect on body weight and body fat	Few safety concerns reported Reported adverse effects: Diarrhea, gas, bloating, and (possibly) decreased high-density lipoprotein levels
Raspberry ketone	Alters lipid metabolism	Studied only in combination with other ingredients Research findings: Insufficient research to draw firm conclusions	No safety concerns reported but not rigorously studied Reported adverse effects: None known
White kidney bean (Phaseolus vulgaris)	Interferes with breakdown and absorption of carbohydrates by acting as a “starch blocker”	Several clinical trials of varying methodological quality Research findings: Possible modest effect on body weight and body fat	Few safety concerns reported Reported adverse effects: Headache, soft stools, flatulence, and constipation
Yohimbe (Pausinystalia yohimbe, yohimbine)	Has hyperadrenergic effects	Very little research on yohimbe for weight-loss Research findings: No effect on body weight; insufficient research to draw firm conclusions	Significant safety concerns reported Reported adverse effects: Headache, anxiety, agitation, hypertension, and tachycardia

* References to support statements in Table 1 are provided in subsequent text.
+Listed in order of severity, with the most severe reported side effects listed last.

 

1) Bitter orange (synephrine)

Bitter orange is the common name for the botanical Citrus aurantium. This plant is a source of p-synephrine (often referred to simply as synephrine) and other protoalkaloids ¹⁵, ¹⁶, ¹⁷, ¹⁸. As alpha-adrenergic agonists, synephrine alkaloids can mimic the action of epinephrine and norepinephrine. However, the extent to which bitter orange and synephrine cause similar cardiovascular and central-nervous-system effects to epinephrine and norepinephrine (e.g., increased heart rate and blood pressure) is not clear.

Studies suggest that bitter orange increases energy expenditure and lipolysis and that it acts as a mild appetite suppressant ¹⁵, ¹⁹. After the FDA banned the use of ephedrine alkaloids in dietary supplements in 2004 (see section on ephedra [ma huang]), manufacturers replaced ephedra with bitter orange in many products; thus, bitter orange became known as an “ephedra substitute” ²⁰. Although synephrine has some structural similarities to ephedrine, it has different pharmacological properties.

Efficacy: Several small human studies have examined whether bitter orange is effective for weight loss ²¹. Interpreting the results of these studies is complicated by the fact that bitter orange is almost always combined with other ingredients in weight-loss supplements.

In one study, 20 healthy overweight adults (body mass index [BMI] >25) took a product containing 975 mg bitter orange extract (6% synephrine alkaloids), 528 mg caffeine, and 900 mg St. John’s wort; a placebo; or nothing (control) each day for 6 weeks ²². All participants also took part in a circuit-training exercise program and were counseled to follow an 1,800 kcal/day diet. At the end of the study, participants taking the combination bitter orange product had a significantly greater reduction in percent body fat and fat mass and a greater increase in basal metabolic rate than those in the placebo and control groups. Participants in all groups lost weight, but the authors did not report whether the mean reduction in body weight in the treatment group (1.4 kg) was significantly greater than that in the placebo (0.9 kg) or control groups (0.4 kg) ²³.

In another study, 8 healthy overweight or obese people (BMI 25–40) received counseling to follow a 1,200–1,500 kcal/day diet and were randomized to take either an herbal supplement containing bitter orange (18 mg synephrine/day) and other ingredients, including guarana extract as a source of caffeine (396 mg caffeine/day), or placebo ²⁴. The peak rise in resting metabolic rate at baseline was significantly higher in participants taking the herbal supplement than those in the placebo group, but the difference was not significant at the end of the 8-week study. The herbal supplement also produced a significant increase in mean body weight (1.13 kg) compared with placebo (0.09 kg) at the end of the study. However, this increase in body weight did not significantly affect body fat and lean tissue levels or waist circumference. The authors noted that the weight gain might have occurred by chance because the trial was insufficiently powered to detect this small difference.

The authors of a 2012 review of 23 small human clinical studies involving a total of 360 participants concluded that synephrine increases resting metabolic rate and energy expenditure ¹⁹. The authors of an earlier review of animal studies, clinical trials, physiologic studies, and case reports concluded that synephrine alkaloids have a “suggestion of some benefit to weight loss,” but the available data are very limited and cannot be considered conclusive ¹⁵. The authors of both reviews stated that longer-term clinical trials with rigorous designs and large samples are needed to determine the value of bitter orange for weight loss.

Safety: Products containing bitter orange have significant safety concerns. Reported adverse effects include chest pain, anxiety, ventricular fibrillation, ischemic stroke, myocardial infarction, and death ²⁵. However, many of the products with these effects contained multiple herbal ingredients, and the role of bitter orange in these adverse effects cannot be determined. Some studies indicate that bitter orange and synephrine—as bitter orange extract or pure synephrine–—raise blood pressure and heart rate in humans and rats, but other studies show that they do not have these effects ²⁶, ²⁷, ²⁸, ²⁹. Thus, some researchers have suggested that synephrine might not act directly as a cardiovascular stimulant [18,27,29]. Instead, caffeine, other stimulants in multi-component formulations, other constituents of bitter orange or adulterants, such as m-synephrine (which is not naturally present in bitter orange), might be responsible for its observed effects.

2) Caffeine, including caffeine from guarana, kola nut, yerba mate, or other herbs

Caffeine (either added to a weight-loss supplement or as an herbal source that naturally contains caffeine, such as guarana (Paullinia cupana), kola (or cola) nut (Cola nitida), and yerba mate (Ilex paraguariensis), is commonly found in dietary supplements promoted for weight loss. Green tea and other forms of tea also contain caffeine (see section on green tea). Some weight-loss supplement labels do not declare the amount of caffeine in the product, only the herbal ingredients. As a result, consumers might not be aware that the presence of certain herbs means that a product contains caffeine and possibly other stimulants ³⁰.

Caffeine is a methylxanthine that stimulates the central nervous system, heart, and skeletal muscles. It also increases gastric and colonic activity and acts as a diuretic ³¹, ³². Its half-life is about 6 hours. Caffeine increases thermogenesis in a linear, dose-dependent fashion in humans ³³. A 100 mg dose of caffeine, for example, increased energy expenditure by a mean of 9.2 kcal/hr more than placebo in healthy humans. Caffeine might also contribute to weight loss by increasing fat oxidation through sympathetic activation of the central nervous system and by acting as a diuretic. Habitual use of caffeine however, may diminish these effects due to the development of caffeine tolerance.

Efficacy: Clinical trials examining the effects of caffeine on weight loss have all been short term and have used combination products. In one study, 167 overweight or obese participants (BMI 25–40) took a supplement containing ma huang (90 mg/day ephedrine) and kola nut (192 mg/day caffeine) or placebo ³⁴. Participants were counseled to eat a normal diet except for limiting dietary fat to 30% of calories and to exercise moderately. After 6 months, those in the treatment group lost significantly more weight (mean weight loss 5.3 kg) than those in the placebo group (2.6 kg) and had significantly greater body fat reduction.

In another study, 47 overweight adults (BMI 26–30) were randomized to take a combination product containing 336 mg yerba mate (1-1.5% caffeine), 285 mg guarana (3–6% caffeine), and 108 mg damiana (a botanical extract that contains ethereal oils, resins, and tannins but not caffeine) or placebo 15 minutes before each main meal for 45 days while maintaining their normal eating habits ³⁵. At the end of the study, participants taking the herbal product lost a mean of 5.1 kg compared to 0.3 kg for those taking the placebo.

Data from a 12-year prospective observational study provide some insight into the long-term association between caffeine intake and body weight ³⁶. In this study, researchers followed 18,417 healthy men and 39,740 healthy women who were enrolled in either the Nurses’ Health Study or the Health Professionals Follow-Up Study. On average, participants gained some weight during the study, but men who increased their caffeine intake during the 12 years of follow-up gained a mean of 0.43 kg less than those who decreased their caffeine consumption. For women, the corresponding mean difference in weight gain was 0.35 kg less.

Safety: For healthy adults, the FDA states that 400 mg/day caffeine is “not generally associated with dangerous, negative effects” ³⁷. For comparison, an 8- ounce cup of brewed coffee contains about 85 mg caffeine ³⁸. The FDA has not set a safe level of intake for children, but the American Academy of Pediatrics discourages children and adolescents from consuming caffeine and other stimulants.

Caffeine can cause sleep disturbances and feelings of nervousness, jitteriness, and shakiness. Caffeine can be toxic when used in high doses, causing nausea, vomiting, tachycardia, seizures, and cerebral edema ³¹. Toxic effects have been reported with doses of 15 mg/kg (about 1,000 mg for a 150-lb adult) and fatalities with doses above 150 mg/kg (about 10,000 mg for a 150-lb adult). Combining caffeine with other stimulants, such as bitter orange and ephedrine, can potentiate these adverse effects.

3) Calcium

Calcium is an essential mineral that is stored in the bones and teeth, where it supports their structure and function. Calcium is required for vascular contraction and vasodilation, muscle function, nerve transmission, intracellular signaling, and hormonal secretion ³⁹. The Recommended Dietary Allowance (average daily level of intake sufficient to meet the nutrient needs of 97%–98% of healthy individuals) for calcium ranges from 1,000 to 1,300 mg/day for children and adults aged 4 years and older.

Several studies have correlated higher calcium intakes with lower body weight or less weight gain over time ⁴⁰, ⁴¹, ⁴², ⁴³. Two explanations have been proposed. First, high calcium intakes might reduce calcium concentrations in fat cells by decreasing the production of parathyroid hormone and the active form of vitamin D. Decreased intracellular calcium concentrations, in turn, might increase fat breakdown and discourage fat accumulation in these cells. Second, calcium from food or supplements might bind to small amounts of dietary fat in the digestive tract and prevent absorption of this fat. Dairy products, in particular, might contain additional components that have even greater effects on body weight than their calcium content alone would suggest ⁴⁴, ⁴⁵, ⁴⁶, ⁴⁷.

Efficacy: The results from clinical trials examining the effects of calcium on body weight have been largely negative. For example, supplementation with 1,500 mg/day calcium (from calcium carbonate) was investigated in 340 overweight or obese adults (BMI ≥25) with mean baseline calcium intakes of 878 mg/day (treatment group) and 887 mg/day (placebo group) ⁴⁸. Compared to placebo, calcium supplementation for 2 years had no clinically significant effects on weight. Three reviews of published studies on the effects of calcium from supplements or dairy products on weight management produced similar conclusions ⁴⁹, ⁵⁰, ⁵¹. The authors of a 2006 meta-analysis of 13 randomized controlled trials concluded that neither calcium supplementation nor increased dairy product consumption has a statistically significant effect on weight reduction ⁵¹. A 2009 evidence report from the Agency for Healthcare Research and Quality showed that, overall, clinical trial results do not support an effect of calcium supplementation on weight ⁴⁹. Also, a 2012 meta-analysis of 29 randomized controlled trials found no benefit of increased consumption of dairy products on body weight and fat loss in long-term studies ⁵⁰. Overall, the results from clinical trials do not support a link between higher calcium intakes and lower body weight, prevention of weight gain, or weight loss.

Safety: The Tolerable Upper Intake Level (UL; maximum daily intake unlikely to cause adverse health effects) for calcium established by the Institute of Medicine of the National Academies is 2,500 mg/day for adults aged 19–50 years and 2,000 mg for adults aged 51 and older ³⁹. High intakes of calcium can cause constipation and might interfere with the absorption of iron and zinc, although this effect is not well established. High intakes of calcium from supplements, but not foods, have been associated with an increased risk of kidney stones ³⁹, ⁵², ⁵³, ⁵⁴.

4) Chitosan

Chitosan is a polysaccharide derived from the exoskeletons of crustaceans. It is purported to promote weight loss by binding dietary fat in the digestive tract [30]. However, the amount of fat that chitosan binds is clinically insignificant ⁵⁵.

Efficacy: In a small study, 12 healthy men and 12 healthy women (BMI 20–36) followed the same diet for 12 days (five meals per day with 38% of energy from fat). Chitosan capsules taken before meals (total of 2.5 g/day) slightly increased fecal fat excretion in the men compared to the control group ⁵⁵. However, the amount of fat that the chitosan trapped would result in a loss of only 1 pound of body fat over about 7 months. Chitosan had no significant effect on fecal fat excretion in the women compared to the control group.

One clinical trial randomly assigned 59 overweight or obese women (BMI 27–40) to receive either chitosan (3 g/day divided between the two largest meals) or placebo for 8 weeks while continuing their normal dietary and exercise habits ⁵⁶. At the end of the study, those in the treatment group lost a mean of 1 kg body weight compared to a mean weight gain of 1.5 kg in the placebo group. In a 28-day trial, chitosan (2 g/day divided into two equal doses) failed to reduce body weight compared to placebo in 28 overweight women and 6 overweight men who maintained their normal diet during the study ⁵⁷. The authors of a Cochrane review that included 13 trials examining the effect of chitosan on body weight found that chitosan, when taken for 4 weeks to 6 months, reduced body weight by a mean of 1.7 kg compared with placebo ⁵⁸. They concluded that chitosan appears to be more effective than placebo for short-term weight loss, but most studies have been of poor quality. The authors noted that results from high-quality trials indicate that chitosan has minimal effects on body weight and these effects are probably clinically insignificant.

Safety: The adverse effects of chitosan are minor and primarily affect the gastrointestinal tract. These effects include flatulence, bloating, mild nausea, constipation, indigestion, and heartburn. Because chitosan is derived from shellfish, people who are allergic to shellfish could theoretically be allergic to chitosan ⁵⁹.

5) Chromium Picolinate

Chromium in its trivalent form (chromium III) is an essential trace mineral that potentiates the action of insulin. The Institute of Medicine of the National Academies has established an Adequate Intake for chromium of 20–35 mcg/day for non-pregnant, non-lactating adults ⁶⁰. Dietary supplements commonly contain chromium in the form of chromium picolinate, which consists of chromium and picolinic acid, although they might also contain other forms, including chromium nicotinate and chromium yeast ⁶¹. Poor chromium status may contribute to impaired glucose tolerance and type 2 diabetes ⁶⁰. Researchers have hypothesized that chromium supplements increase lean muscle mass and promote fat loss, but study results have been equivocal ³⁰, ⁶². Some research indicates that these supplements might also reduce food intake, hunger levels, and fat cravings [66], although data on these effects are sparse.

Efficacy: Several studies have evaluated the effects of chromium supplements, usually in the form of chromium picolinate, on weight loss. A 2013 Cochrane review analyzed the results from 9 randomized controlled trials of chromium picolinate supplements in a total of 622 overweight or obese participants (BMI ≥25) ⁶². Trial durations ranged from 8 weeks to 6 months, and doses of chromium picolinate were 200 to 1,000 mcg/day. Six of the trials included resistance or weight training, and three did not. The authors found that chromium picolinate supplementation reduced body weight by 1.1 kg more than placebo, but the amount of weight loss did not correlate with the dose of chromium picolinate. The authors stated that the effect is of “debatable clinical relevance” and the overall quality of the evidence is low.

Also in 2013, a systematic review and meta-analysis of 11 randomized, controlled trials (including most of the trials evaluated in the Cochrane review) examined the effects of chromium supplementation in a total of 866 overweight or obese individuals ⁶¹. The authors concluded that chromium reduces body weight by 0.5 kg and percent body fat by 0.46% when taken at daily doses of 137 to 1,000 mcg for 8 to 26 weeks. Like the authors of the Cochrane review, these authors noted that the effect is small and of “uncertain” clinical relevance. Similar findings were reported from an earlier meta-analysis of 12 trials ⁶³.

Safety: Trivalent chromium appears to be well tolerated. Adverse effects from clinical trials include watery stools, headache, weakness, nausea, vomiting, constipation, vertigo, and urticaria (hives). Chromium does not have an established UL because few serious adverse effects have been linked to high chromium intakes. Hexavalent chromium (chromium IV) is toxic and is not found in food or dietary supplements.

6) Coleus forskohlii (forskolin)

Forskolin is a compound isolated from the roots of Coleus forskohlii, a plant that grows in subtropical areas, such as India and Thailand. Forskolin is purported to promote weight loss by enhancing lipolysis and reducing appetite ⁶⁴, ⁶⁵.

Efficacy: Although animal studies indicate that forskolin reduces food intake ⁶⁴, research in humans is very limited and inconclusive. In a small, randomized, double- blind trial, 19 overweight or obese females (BMI 25–35) aged 18–40 years received either forskolin (250 mg of 10% forskolin extract taken before breakfast and dinner for a total daily dose of 500 mg) or placebo while continuing their usual diet for 12 weeks ⁶⁶. Compared to placebo, forskolin had no effect on body weight, appetite, caloric intake, or macronutrient intake. The same forskolin product and dose were evaluated in another 12-week, randomized, double-blind trial involving 30 overweight men (BMI ≥26) ⁶⁵. In this study, forskolin did not affect body weight, but it did significantly decrease mean body fat by 4.14% compared with placebo (0.96%).

Safety: No significant adverse events were reported in the two 12-week trials detailed above, but forskolin has not been evaluated in longer-term trials. Additional research is needed to better understand its safety and side effects for both short- and long-term use.

7) Conjugated Linoleic Acid (CLA)

Conjugated linoleic acid (CLA) is a derivative of linoleic acid that is present mainly in dairy products and beef. CLA exists in several different isomeric forms, including c9t11 -CLA and t10c12-CLA, and is available in dietary supplements as a triacylglycerol or as a free fatty acid ⁶⁷. Researchers have suggested that CLA enhances weight loss by promoting apoptosis in adipose tissue ⁶⁸.

Efficacy: Although CLA appears to reduce body fat mass in animals ⁶⁸, results from human studies suggest that its effects are small and of questionable clinical relevance ⁶⁹. One double-blind, placebo-controlled trial evaluated the effects of CLA supplementation (as a 50:50 mixture of c9t11-CLA and t10c12-CLA) in 180 overweight male and female volunteers (BMI 25–30) consuming an ad libitum diet ⁶⁷. Participants received CLA as a free fatty acid (3.6 g CLA isomers), CLA as a triacylglycerol (3.4 g CLA isomers), or placebo daily for 1 year. At the end of the study, supplementation with CLA as a free fatty acid and as a triacylglycerol significantly reduced body fat mass by a mean of 6.9% and 8.7%, respectively, compared with placebo. Supplementation with CLA as a free fatty acid (but not as a triacylglycerol) also increased lean body mass compared with placebo.

In another double-blind crossover trial, daily supplementation with CLA oil (6.4 g CLA isomers—approximately equal amounts of c9t11-CLA and t10c12-CLA) for 16 weeks significantly reduced BMI and total adipose mass compared with safflower oil in 35 obese postmenopausal women (BMI >30) with type 2 diabetes⁷⁰.

The authors of a systematic review and meta-analysis of 7 randomized controlled trials concluded that taking CLA for 6–12 months reduces body weight by a mean of 0.7 kg and body fat by a mean of 1.33 kg compared to placebo ⁶⁹. However, the authors noted that the “magnitude of these effects is small, and the clinical relevance is uncertain.”

Safety: CLA appears to be well tolerated. Most reported adverse effects are minor, consisting mainly of gastrointestinal disturbances, such as abdominal discomfort and pain, constipation, diarrhea, loose stools, and dyspepsia ⁷¹.

CLA might adversely affect lipid profiles, although results from studies are inconsistent. Some research indicates that CLA has no major effect on lipid profiles, but other research shows that certain CLA isomers might decrease high-density lipoprotein (HDL) cholesterol and increase lipoprotein(a) levels ⁶⁷, ⁷¹, ⁷², ⁷³, ⁷⁴, ⁷⁵. The CLA isomer t10c12-CLA has also been reported to increase insulin resistance and glycemia in obese men with metabolic syndrome ⁷⁵.

8) Ephedra (ma huang) – banned by the FDA since 2004

Ephedra (also known as ma huang), a plant native to China, is the common name for three main species: Ephedra sinica, Ephedra equisentina, and Ephedra intermedia ⁷⁶. The active compounds, which are in the plant’s stem and account for about 1.32% of the plant’s weight, are the alkaloids ephedrine, pseudoephedrine, norephedrine, and norpseudoephedrine ⁷⁷, ⁷⁸.

In the 1990s, ephedra—frequently combined with caffeine—was a popular ingredient in dietary supplements sold for weight loss and enhanced athletic performance. The FDA no longer permits the use of ephedra in dietary supplements because of safety concerns that are detailed below, but information is provided here due to continued interest in this ingredient.

In 2004, the FDA banned the U.S. sale of dietary supplements containing ephedra. The FDA found that these supplements had an unreasonable risk of injury or illness—particularly cardiovascular complications—and a risk of death.

Efficacy: Ephedrine acts as a stimulant in the central nervous system. It also may increase thermogenesis and act as an appetite suppressant. The authors of a meta-analysis that included 20 clinical trials concluded that ephedrine and ephedra are modestly effective for short-term weight loss (6 months or less), but no studies have assessed their long-term effects.

Safety: While ephedra was available as a dietary supplement ingredient in the United States, its use with or without caffeine was associated with numerous reported adverse effects, including nausea, vomiting, psychiatric symptoms (such as anxiety and mood change), hypertension, palpitations, stroke, seizures, heart attack, and death ⁷⁹, ⁸⁰. Although these reported adverse effects could not be linked with certainty to the use of ephedra-containing dietary supplements, the FDA deemed the safety concerns serious enough to prohibit the sale of dietary supplements containing ephedrine alkaloids in 2004 ⁸¹. As a result of this ruling, manufacturers are no longer permitted to sell dietary supplements containing ephedrine alkaloids in the United States.

9) Fucoxanthin

Fucoxanthin is a carotenoid that is found in brown seaweed and other algae. Results from laboratory and animal studies suggest that fucoxanthin might promote weight loss by increasing resting energy expenditure and fatty acid oxidation as well as by suppressing adipocyte differentiation and lipid accumulation ⁸², ⁸³.

Efficacy: Only one human clinical trial has been conducted on the possible weight-loss effects of fucoxanthin. This 16-week trial used Xanthigen®, a dietary supplement containing brown seaweed extract and pomegranate-seed oil ⁸⁴. In one arm of this study, 110 obese (BMI >30) premenopausal women, 72 of whom had non-alcoholic fatty liver disease (NAFLD), received either a placebo or Xanthigen® three times a day before meals for a total daily dose of 2.4 mg fucoxanthin and 300 mg pomegranate-seed oil. Participants followed a controlled diet that limited total energy intake to 1,800 kcal/day. Compared to the placebo group, those receiving Xanthigen® lost significantly more body weight by the end of the trial (mean loss of 6.9 kg vs. 1.4 kg for placebo in participants with NAFLD; mean loss of 6.3 kg vs. 1.4 kg for placebo in those without NAFLD). Because this is the only clinical trial on a dietary supplement containing fucoxanthin, additional research is needed to understand its potential effects on body weight.

Safety: The safety of fucoxanthin has not been thoroughly evaluated in humans. Although participants using Xanthigen® in the clinical trial described above reported no adverse effects ⁸⁴, further investigation of the safety and potential side effects of fucoxanthin at various levels of intake is required.

10) Garcinia cambogia (hydroxycitric acid)

Garcinia cambogia is a fruit-bearing tree that grows throughout Asia, Africa, and the Polynesian islands ⁸⁵. The pulp and rind of its fruit contain high amounts of hydroxycitric acid (HCA), a compound that some researchers believe inhibits lipogenesis, increases hepatic glycogen synthesis, suppresses food intake, and reduces weight gain ⁸⁵, ⁸⁶.

Efficacy: Studies in rats have found that Garcinia cambogia suppresses food intake and inhibits weight gain. In humans, however, the evidence on whether Garcinia cambogia or HCA is effective for weight loss is conflicting, and any effects it has appear to be small ⁸⁵, ⁸⁶, ⁸⁷.

In one randomized, placebo-controlled trial, 89 mildly overweight women (weighing 10–50 lb more than ideal body weight) received Garcinia cambogia (800 mg, 30–60 minutes before meals for a total daily dose of 2.4 g/day [1.2 g HCA]) or placebo and followed a 1,200 kcal diet for 12 weeks ⁸⁸. Women receiving Garcinia cambogia lost significantly more weight (3.7 kg) than those receiving placebo (2.4 kg). However, Garcinia cambogia did not alter appetite, and the study produced no evidence that the supplement affected feelings of satiety. In another double-blind, placebo-controlled trial, 135 overweight men and women (BMI 27–38) received either Garcinia cambogia (1,000 mg, 30 minutes before each meal for a total daily dose of 3,000 mg/day [1,500 mg HCA]) or placebo and followed a high-fiber, low-energy diet for 12 weeks ⁸⁹. Participants in both groups lost weight, but the between-group weight-loss differences were not statistically significant. HCA also had no effect on body fat loss.

A 2011 review and meta-analysis of 12 randomized, controlled trials with a total of 706 participants examined the effects of HCA on weight loss ⁹⁰. The findings from 9 of the trials (those that had data suitable for statistical pooling) indicate that when taken for 2–12 weeks, HCA reduces body weight in the short term by a mean of 0.88 kg compared to placebo. However, the authors noted that when they considered only rigorously designed trials, the effect was no longer statistically significant. Therefore, the effect of HCA on body weight remains uncertain. The authors of a 2013 review of Garcinia cambogia/HCA reached similar conclusions, noting that whether Garcinia cambogia/HCA is effective for obesity “remains to be proven in larger-scale and longer-term clinical trials” ⁹¹.

Safety: The reported adverse effects of Garcinia cambogia and HCA are generally mild and include headache, nausea, upper respiratory tract symptoms, and gastrointestinal symptoms. Cases of liver toxicity have been reported in people taking products containing Garcinia cambogia, other botanical ingredients, and minerals. However, it is unclear whether this toxicity can be attributed to Garcinia cambogia. Because all clinical trials of Garcinia cambogia and HCA have been short, its long-term safety is unknown.

11) Glucomannan

This is made from the konjac plant. Like other dietary fibers, it’s supposed to help you lose weight by blocking fat in your food from being absorbed into your body.

Glucomannan is a soluble dietary fiber derived from konjac root (Amorphophallus konjac). Some researchers believe that, like guar gum, glucomannan absorbs water in the gastrointestinal tract, thereby increasing feelings of satiety and fullness and prolonging gastric emptying ⁹², ⁹³.

Efficacy: Glucomannan appears to have beneficial effects on blood lipids and glucose levels ⁹³, but its effects on weight loss are inconsistent. In one study conducted in Italy, 2 g/day glucomannan (in 2 divided doses) in 60 obese children (mean age 11.2 years) for 2 months did not significantly affect weight loss compared to placebo ⁹⁴. In a small study conducted in the United States, 20 obese women (weighing ≥20% more than ideal body weight) consumed 3 g/day glucomannan (1 g before each meal) or placebo for 8 weeks ⁹⁵. At the end of the study, glucomannan produced significantly greater weight loss (mean loss of 2.5 kg) than placebo (mean gain of 0.7 kg). In another study conducted in the United States, supplementation with glucomannan (3.9 g/day) for 4 weeks in 63 healthy men did not significantly affect body weight compared with placebo ⁹⁶.

The authors of a 2015 systematic review of six randomized controlled trials with a total of 293 participants concluded that 1.24 to 3.99 g/day glucomannan for up to 12 weeks does not have a significant effect on body weight compared to placebo ⁹⁷, ⁹⁸. Similarly, a 2014 meta-analysis of eight trials that included 301 participants found that glucomannan did not significantly affect weight loss compared to placebo ⁹⁹. The authors of an older meta-analysis of 14 studies designed primarily to investigate glucomannan’s effect on lipid and blood glucose levels concluded that 1.2 to 15.1 g/day glucomannan reduces body weight by a small but statistically significant amount (mean loss 0.79 kg more than placebo) over about 5 weeks ⁹³.

Safety: Little is known about the long-term safety of glucomannan. Glucomannan appears to be well tolerated for short-term use, with minor adverse effects including loose stools, flatulence, diarrhea, constipation, and abdominal discomfort. The use of tablet forms of glucomannan was reported to be associated with seven cases of esophageal obstruction in 1984–1985 in Australia ⁹². Caution is therefore warranted when these forms of glucomannan are used. Powdered or capsule forms have not been associated with this effect.

12) Green coffee bean extract (Coffea aribica, Coffea canephora, Coffea robusta)

Coffee beans (Coffea aribica, Coffea canephora, Coffea robusta) are green until they are roasted. Compared to roasted beans, green coffee beans have higher levels of chlorogenic acid. Green coffee extract, likely due to its chlorogenic acid content, has been shown in mice and humans to inhibit fat accumulation and modulate glucose metabolism ¹⁰⁰, perhaps by reducing the absorption of glucose in the gut ¹⁰¹. Green coffee beans also contain caffeine (see section on caffeine above).

Efficacy: Only a few clinical trials have examined the effects of green coffee bean on weight loss, and all are of poor methodological quality. Onakpoya and colleagues conducted a meta-analysis of three trials in which overweight participants received either 180 or 200 mg/day green coffee extract for 4 to 12 weeks ¹⁰¹. The researchers concluded that green coffee extract has a moderate but significant effect on body weight (mean weight loss of 2.47 kg more than placebo), but they noted that the methodological quality of all studies included in the meta-analysis was poor.

Another small clinical trial claimed to show a benefit of green coffee extract for weight loss  ¹⁰², but it was strongly criticized by the FTC for having several critical flaws in the study design. Two of the three study authors subsequently retracted the journal publication.

Safety: Green coffee extract appears to be well tolerated, but its safety has not been rigorously studied. Reported adverse effects include headaches and urinary tract infections. The caffeine in green coffee beans acts as a stimulant and can cause adverse effects, depending on the dose and whether it is combined with other stimulants (see section on caffeine above).

 

13) Green tea (Camellia sinensis) and green tea extract

Green tea (Camellia sinensis) is a popular beverage consumed worldwide that has several purported health benefits ¹⁰³. Green tea is present in some dietary supplements, frequently in the form of green tea extract. The active components of green tea that are associated with weight loss are caffeine (see section on caffeine above) and catechins, primarily epigallocatechin gallate (EGCG), which is a flavonoid. A typical brewed cup of green tea has about 240–320 mg catechins ¹⁰³ and 45 mg caffeine. Experts have suggested that green tea and its components might reduce body weight by increasing energy expenditure and fat oxidation, reducing lipogenesis, and decreasing fat absorption ¹⁰⁴, ¹⁰⁵.

The authors of a meta-analysis of 6 randomized controlled trials with a total of 98 participants found that caffeine alone or in combination with catechins significantly increases energy expenditure in a dose-dependent fashion compared with placebo ¹⁰⁴. This effect might be important for maintaining weight loss by helping to counteract the decrease in metabolic rate that can occur during weight loss. Catechins combined with caffeine also significantly increase fat oxidation, but caffeine alone does not. Other human research indicates that EGCG alone does not increase resting metabolic rate, fat oxidation, or the thermic effect of feeding (the increase in metabolic rate associated with the digestion and absorption of food) ¹⁰⁶, ¹⁰⁷.Taken together, these findings suggest that green tea catechins and caffeine might act synergistically.

Efficacy: Several human studies have examined the effects of green tea catechins on weight loss and weight maintenance. A 2012 Cochrane review analyzed the results from 14 randomized controlled trials of green tea preparations in a total of 1,562 overweight or obese participants ¹⁰⁸. The trials lasted from 12 to 13 weeks, and doses of green tea catechins ranged from 141 to 1,207 mg. Green tea supplementation reduced body weight by a mean of 0.95 kg more than placebo. However, when the authors analyzed the six studies that were conducted outside of Japan (where study methodologies were less heterogeneous than in the Japanese studies), they found no statistically significant difference in weight loss for green tea compared to placebo.

Another systematic review and meta-analysis included 15 randomized controlled trials, 6 of which examined the effects of caffeine (39–83 mg/day) with and without green tea catechins (576–690 mg/day) on anthropometric measurements. The authors reported that green tea catechins combined with caffeine over a median of 12 weeks modestly yet significantly reduced body weight by a mean of 1.38 kg and waist circumference by a mean of 1.93 cm compared with caffeine alone ¹⁰⁹. Only two studies in this meta-analysis examined the effects of green tea catechins alone. Their results suggest that green tea catechins alone do not affect body weight or other anthropometric measurements.

A similar meta-analysis of 11 randomized controlled trials found that people who took EGCG combined with caffeine for 12–13 weeks lost a mean of 1.31 kg more body weight (or gained 1.31 kg less weight) than those in control groups ¹¹⁰. In 2010, the European Food Safety Authority examined health claims related to green tea and concluded that “a cause and effect relationship has not been established between the consumption of catechins (including EGCG) from green tea…and contribution to the maintenance or achievement of a normal body weight.” ¹¹¹. Taken together, the findings of these studies suggest that if green tea is an effective weight-loss aid, any effect it has is small and not likely to be clinically relevant ¹⁰⁸, ¹⁰⁹.

Safety: No adverse effects have been reported from the consumption of green tea as a beverage. For green tea extract, most reported adverse effects are mild to moderate, including nausea, constipation, abdominal discomfort, and increased blood pressure ¹¹². However, consumption of green tea extract—primarily ethanolic extracts of green tea—has been linked to liver damage in several case reports. These reports prompted the U.S. Pharmacopeia (USP) to systematically review the safety of green tea products in 2008 ¹¹³. Using clinical case report data and animal pharmacological and toxicological information, the USP concluded that the consumption of green tea products “probably” caused 7 cases of liver damage and “possibly” caused another 27 cases. The USP noted that problems are more likely to occur when green tea extract is taken on an empty stomach and therefore, advises taking green tea extracts with food to minimize the possible risk of liver damage. Other research indicates that green tea polyphenols do not elevate liver enzymes or cause liver dysfunction when consumed by healthy men for 3 weeks at a dose of 714 mg/day ¹¹⁴. Liver damage from green tea extracts could be partly due to contaminants in some products, but some researchers advise using dietary supplements containing green tea extract with caution.

14) Guar Gum

 

Guar gum is a soluble dietary fiber derived from the Indian cluster bean Cyamopsis tetragonolobus ¹¹⁵. Guar gum is present in certain dietary supplements and is an ingredient in some food products, especially gluten-free baked goods, because it helps bind and thicken these products. Like glucomannan, guar gum is purported to promote weight loss by acting as a bulking agent in the gut, delaying gastric emptying, increasing feelings of satiety, and, theoretically, decreasing appetite and food intake ¹¹⁵.

Efficacy: In a meta-analysis of 20 randomized, double-blind, placebo-controlled trials that statistically pooled data from 11 trials, Pittler and colleagues evaluated the effects of guar gum for body weight reduction in a total of 203 adults ¹¹⁵. Trial participants included people with hypercholesterolemia, hyperlipidemia, or type 1 or type 2 diabetes; menopausal women; and healthy volunteers. Doses of guar gum ranged from 9 to 30 g/day; most participants followed their usual diet, and some received dietary advice. Compared with placebo, guar gum had no significant effect on weight loss. The authors concluded that guar gum is not effective for body weight reduction.

Safety: Reported adverse effects for guar gum are primarily gastrointestinal and include abdominal pain, flatulence, diarrhea, nausea, and cramps [125,126]. Case reports indicate that guar gum can cause severe esophageal and small-bowel obstruction if taken without sufficient fluid ¹¹⁶, ¹¹⁷. However, these reports were about a guar gum product that is no longer available ¹¹⁶. In their meta-analysis, Pittler and colleagues concluded that given the adverse effects associated with the use of guar gum, the risks of taking it outweigh its benefits ¹¹⁵.

15) Hoodia (Hoodia gordonii)

Hoodia gordonii is a succulent plant that grows in the Kalahari Desert of southern Africa. The San people have traditionally used hoodia as an appetite suppressant during long hunts. This anecdotal evidence, combined with results of a few animal studies indicating that hoodia reduces food intake ¹¹⁸, led to the widespread marketing of hoodia as a weight-loss supplement in the United States.

Efficacy: Despite its immense popularity as a weight-loss supplement, very little scientific research on hoodia has been conducted in humans ¹¹⁹ and a mechanism of action for its potential weight-loss effects has not been proposed. In a randomized, controlled trial, 49 healthy overweight women (mean BMI 25) aged 18–50 years were randomized to receive Hoodia gordonii purified extract (2,220 mg/day in two divided doses taken 1 hour before breakfast and dinner) or placebo combined with an ad libitum diet for 15 days ¹²⁰. Compared to placebo, hoodia extract had no significant effect on energy intake or body weight.

Safety: Hoodia has been reported to cause significant increases in heart rate and blood pressure ¹²⁰. It also raises bilirubin and alkaline phosphatase levels (which may indicate impaired liver function), although the clinical significance of these findings is unclear because hoodia has not been reported to affect levels of other liver enzymes. Other side effects include headache, dizziness, nausea, and vomiting.

Various news reports indicate that some hoodia products contain little or no hoodia ¹²¹. According to a report released in 2007, only 30%–60% of hoodia products contain adequate amounts of hoodia, although the authors did not indicate whether “adequate” refers to a therapeutic dose or indicates that the quantity of hoodia matches the label claim ¹²²; more recent data on hoodia content in supplements are not available.

16) Pyruvate

Pyruvate (a derivative of pyruvic acid) is a three-carbon compound that is generated in the body through glycolysis ¹²³. Pyruvate is also available as a dietary supplement, frequently in the form of calcium pyruvate. Researchers have suggested that pyruvate enhances exercise performance and reduces body weight and body fat, possibly by increasing lipolysis and energy expenditure ¹²⁴, ¹²⁵.

Efficacy: Only a few studies have examined the effects of pyruvate supplementation in humans. Although some of these studies suggest that pyruvate decreases body weight and body fat, others do not. In a double-blind, placebo-controlled trial, 26 overweight men and women (BMI ≥25) were given 6 g/day pyruvate or placebo for 6 weeks ¹²³. All participants received counseling to follow a 2,000 kcal/day diet and completed 45–60 minutes of circuit training 3 times per week. At the end of the trial, the pyruvate group had significant decreases in body weight (mean loss of 1.2 kg), body fat, and percent body fat compared to baseline but no significant changes in lean body mass. In the placebo group, these measurements did not change significantly compared to baseline.

Another small study of 14 obese women (BMI 28–53) found that pyruvate produces greater weight loss and fat loss when isoenergetically substituted for a glucose placebo for 21 days as part of a low-energy diet ¹²⁶. However, a double-blind, placebo-controlled trial in 23 overweight women (mean BMI 27.4) who followed their normal diets and participated in weight training and 30 minutes of walking 3 times per week had a different outcome ¹²⁵. In this trial, supplementation with 5 g/day calcium pyruvate for 30 days did not significantly affect body weight, body fat, percent body fat, or lean body mass compared with placebo. The authors of a systematic review and meta-analysis of 6 randomized controlled trials in a total of 203 participants concluded that pyruvate (when taken for 3–6 weeks) reduces body weight by a mean of 0.72 kg and body fat by a mean of 0.54 kg compared to placebo ¹²⁴. However, the authors noted that the methodological quality of all trials is weak, preventing them from drawing firm conclusions.

Safety: The safety of pyruvate has not been rigorously studied. Pyruvate causes gas, bloating, diarrhea, and borborygmus (rumbling noise in intestines resulting from gas) but has no serious adverse effects when it is administered for up to 6 weeks. Pyruvate might also increase LDL levels and decrease HDL levels. Additional research is needed to better understand the safety and possible side effects of this compound.

17) Raspberry ketone

 

Raspberry ketone is an aromatic compound found in red raspberries (Rubus idaeus). Its chemical structure has some similarities to those of capsaicin (present in hot red peppers) and synephrine, compounds whose effects on obesity and lipid metabolism have been investigated ¹²⁷. Raspberry ketone might help prevent weight gain by altering lipid metabolism. Although it has been touted on the Internet and national television as an effective way to burn fat, little evidence exists to support this claim.

Efficacy: Only one randomized controlled trial has examined the effects of a dietary supplement containing raspberry ketone and other ingredients. In this trial, 70 overweight men and women aged 21–45 (BMI >27) received daily supplementation with either a placebo or a weight-loss product, Prograde MetabolismTM (METABO) ¹²⁸. This product contained 2,000 mg of a proprietary blend of raspberry ketone, caffeine, bitter orange, ginger, garlic, cayenne, L-theanine, and pepper extract along with B- vitamins and chromium. During the 8-week study, participants followed a calorie-restricted diet (approximately 500 calories less per day than estimated needs) and engaged in moderate exercise (60 minutes, 3 days per week). Compared to the placebo group, those receiving METABO lost significantly more body weight (mean loss of 1.9 kg vs. 0.4 kg for placebo) and fat mass. However, 25 of the 70 participants dropped out of the study, and results were reported for only the 45 participants who completed the study (i.e., the authors did not complete an intention-to-treat analysis). Furthermore, the product contained many ingredients in addition to raspberry ketone, making it impossible to determine the effects of raspberry ketone alone.

Safety: Participants in the METABO study described above had no serious adverse effects ¹²⁸. However, additional research on raspberry ketone is needed to more thoroughly understand its safety and side effects.

18) White kidney bean/bean pod (Phaseolus vulgaris)

White kidney bean or bean pod (Phaseolus vulgaris) is a legume that is native to Mexico, Central America, and South America and is cultivated worldwide ¹²⁹. Phaseolus vulgaris extract is an ingredient in some weight-loss dietary supplements marketed as carbohydrate- or starch-absorption “blockers.” Laboratory research indicates that Phaseolus vulgaris extract inhibits alpha-amylase activity, so experts have hypothesized that the plant interferes with the breakdown and absorption of carbohydrates in the gastrointestinal tract. Phaseolus vulgaris might also act as an appetite suppressant ¹²⁹.

Efficacy: The effect of Phaseolus vulgaris on weight loss and body fat has been examined in a few clinical trials, with inconsistent results. In a randomized, double-blind, placebo-controlled trial conducted in Italy, 60 overweight women (weighing 11–33 lb more than ideal body weight) aged 20–45 followed a 2,000–2,200- calorie meal plan and took a tablet containing approximately 445 mg dried aqueous extract of Phaseolus vulgaris (Phase 2® Starch Neutralizer IV) or a placebo once daily before eating a carbohydrate-rich meal ¹³⁰. After 30 days, those receiving Phaseolus vulgaris extract lost significantly more weight (mean weight loss 2.93 kg) than those receiving placebo (mean weight loss 0.35 kg). Those in the Phaseolus vulgaris group also experienced a significantly greater reduction in fat mass, adipose tissue thickness, and waist–hip–thigh circumference. However, in a similar trial conducted in the United States in 39 overweight adults (mostly women, BMI 30–43) aged 20–69, those who consumed 1,500 mg Phase 2® starch neutralizer twice daily with lunch and dinner (total daily dose 3,000 mg) for 8 weeks with a high-fiber/low-fat diet did not experience significantly greater weight loss than those receiving a placebo ¹³¹.

The authors of a 2011 review of 6 trials (including the 2 trials described above) with a total of 247 participants concluded that Phaseolus vulgaris significantly reduces body fat (mean difference 1.86 kg compared to placebo) but does not significantly affect weight loss ¹²⁹. However, the authors noted that the quality of the trials included in their review was poor, making it impossible to draw firm conclusions.

After the publication of this review, a 12-week clinical trial in 123 overweight and obese men and women found that Phaseolus vulgaris modestly yet significantly reduced body weight and body fat ¹³². Participants consumed either a placebo or 1,000 mg Phaseolus vulgaris (IQP-PV-101; marketed under Phase 2®, Starchlite®, and PhaseliteTM brands) 3 times per day before meals for a total daily dose of 3,000 mg while following a mildly hypocaloric diet (500 kcal/day less than basal energy needs). Compared to placebo, those receiving Phaseolus vulgaris lost significantly more body weight (mean loss of 2.91 kg vs. 0.92 kg for placebo) and body fat (2.23 kg vs. 0.65 kg for placebo).

Safety: Reported adverse effects for Phaseolus vulgaris are fairly minor and include headaches, soft stools, flatulence, and constipation ¹²⁹. No serious adverse effects of Phaseolus vulgaris have been reported in clinical trials, but no trials have lasted longer than 13 weeks.

19) Yohimbe (Pausinystalia yohimbe, yohimbine)

Yohimbe (Pausinystalia yohimbe, Pausinystalia johimbe) is a West African evergreen tree. The tree’s bark contains the alkaloid yohimbine, which is the main active constituent of yohimbe ¹³³. Yohimbine has hyperadrenergic physiological effects because it acts as an alpha-2 receptor antagonist ⁶, ¹³⁴. Yohimbe extract is found in some dietary supplements that are promoted for libido enhancement, body building, and weight loss ¹³³, but it is used primarily as a traditional remedy for sexual dysfunction in men. A form of yohimbine—yohimbine hydrochloride—is a prescription drug used to treat erectile dysfunction ¹³³, ¹³⁵.

Efficacy: Very little research has been conducted on the use of yohimbe for weight loss and/or its effect on body mass. In a small clinical trial, yohimbine (5 mg taken 4 times/day) resulted in greater weight loss (mean weight loss 3.55 kg) than placebo (mean weight loss 2.21 kg) in 20 obese females (mean BMI 40 and 43 for placebo and yohimbine groups, respectively) who followed a low-energy diet (1,000 kcal/day) for 3 weeks ¹³⁶. However, in another clinical trial in 47 men (weighing >20% more than ideal body weight), high-dose yohimbine (peak dose 43 mg/day) for 6 months had no effect on body weight or body fat compared with placebo ¹³⁷. The authors of a 2011 review of yohimbe concluded that no conclusive evidence indicates that yohimbe affects body weight or body mass ¹³⁴. The author of a 2010 review of yohimbe reached similar conclusions, noting that results from small human trials of yohimbine for weight loss are contradictory and the evidence base is insufficient to support a weight loss claim for this compound ¹³³.

Safety: Yohimbe can be dangerous. Taking 20 to 40 mg has been reported to increase blood pressure slightly, whereas doses of 200 mg or higher can cause headaches, hypertension, anxiety, agitation, tachycardia, myocardial infarction, cardiac failure, and death ¹³⁸. Although yohimbe is generally well tolerated at low doses, no safe dose has been established for it. Yohimbe should only be used under medical supervision because of its potential to produce serious adverse effects ¹³⁸.

Safety Considerations

More than 500 supplements have already been found to be adulterated with pharmaceuticals or pharmaceutical analogues, including new stimulants, novel anabolic steroids, unapproved antidepressants, banned weight-loss medications, and untested sildenafil analogues ¹³⁹. In 2013 alone, researchers discovered two new stimulants in widely marketed supplements. Researchers have identified a new analogue of methamphetamine, N,α-diethyl-phenylethylamine (N,α-DEPEA), in a popular sports supplement ¹⁴⁰. FDA scientists discovered another stimulant, β-methylphenethylamine (β-MePEA) — a novel analogue of amphetamine — in nine supplements ¹⁴¹. N,α-DEPEA and β-MePEA have never been studied in humans, and their adverse effects are entirely unknown; yet they are sold as “natural” products without having undergone any premarketing testing for safety. Although supplements containing N,α-DEPEA were voluntarily withdrawn from the market, supplements containing β-MePEA remain widely available. ¹⁴².

Epidemiologists at the Centers for Disease Control and Prevention recently confirmed what an astute liver-transplant surgeon in Honolulu already suspected: OxyElite Pro, a popular over-the-counter supplement, was responsible for a cluster of cases of severe hepatitis and liver failure ¹⁴³. Although patients began to develop severe hepatitis in May 2013, the Food and Drug Administration (FDA), whose job it is to remove dangerous supplements from store shelves, did not learn of the cases until mid-September, 4 months later. By February 2014, the CDC had linked 97 cases, resulting in 47 hospitalizations, three liver transplantations, and one death, to OxyElite Pro. This dietary supplement was recalled, but nothing has been done to prevent another supplement from causing organ failure or death. Nor have any changes been made to improve the FDA’s ability to detect dangerous supplements ¹⁴².

The rate of liver failure caused by dietary supplements has risen 185% in the past decade ¹⁴⁴. In the United States, 16% of cases of serious drug-induced liver injury are attributed to dietary supplements. The vast majority are those sold for weight loss and muscle building ¹⁴⁵.

Drugs found in supplements for weight loss and muscle building have included:

• The active ingredient in Meridia, a prescription weight-loss drug pulled from the market in 2010 ¹⁴⁶,
• Drugs that have been designed to be chemically similar to methamphetamine (aka speed) ¹⁴⁷,
• Antidepressants such as fluoxetine, the active ingredient in Prozac ¹⁴⁸,
• Anabolic steroids and precursor chemicals, which can cause young athletes to fail doping tests and have been associated with testicular cancer ¹⁴⁹,

Many supplements whose labels say they contain “pro-hormones,” “natural steroids,” or “testosterone boosters” actually contain designer anabolic steroids–with dangerous consequences. Use of these compounds through dietary supplements is widespread. In younger men, these supplements may be a common cause of liver injury, problems with bile secretion, testicular disorders, growth of breast tissue, and infertility. Authors advise against dietary supplement use, especially those known or suspected to contain designer steroids ¹⁵⁰.

Recalls are not enough to protect people from supplements containing unlisted, unapproved ingredients. In November 2009, the U.S. Food and Drug Administration banned Pai You Gou, a dietary supplement sold for weight loss, after detecting at least two banned pharmaceutical compounds, sibutramine and phenolphthalein, in this product. Sibutramine and phenolphthalein have serious and well-documented side effects. But almost a year after the recall, nearly one in four Brazilian-born Massachusetts women were still using this product ¹⁵¹.

Dietary supplements marketed for weight loss and muscle building have dangerous side effects, including hepatitis and liver failure. The U.S. Centers for Disease Control and Prevention documented a series of severe acute hepatitis (liver injury) and liver failure of unknown cause. Of the 29 confirmed cases of acute hepatitis and liver failure, 24 patients reported using OxyELITE Pro, a dietary supplement sold for weight loss and muscle gain, within 60 days before illness onset ¹⁵². Dangerous stimulants are often found in widely available supplements for weight loss and muscle building. When one stimulant is banned, supplement makers often continue using the banned substances, or replace them with a related chemical. Many of these chemicals have never been tested for safety in humans.

Researchers found N,α-DEPEA, in a widely available muscle-building supplement. N,α-DEPEA is a banned and potentially dangerous designer stimulant closely related to methamphetamine ¹⁵³.

Half of supplements marketed as containing the herbal ingredient acacia rigidula were found to contain β-methylphenylethylamine (BMPEA). BMPEA is a stimulant that has not been assessed for safety or efficacy in humans. It is closely related to the banned compound DMAA, which has been associated with several deaths ¹⁵⁴.

Another DMAA substitute, 1,3-dimethylbutylamine (DMBA), has also been banned by the FDA. Despite the ban, researchers found at least a dozen supplements to contain DMBA in dosages ranging from 13 to 120 mg per serving ¹⁵⁵.

Muscle-building supplements may lead to increased risk of testicular germ cancer in men. A study of nearly 1000 men found that men who developed testicular germ cancer had used more muscle-building supplements than similar men who did not develop testicular germ cancer. The association was particularly strong among early users, long-term users, and use of two or more types of muscle-building supplements ¹⁵⁶.

Diet pills may block the function of other drugs, including cancer treatments. Diet pills may also be associated with organ toxicity. Research suggests that the diet drug orlistat limits the function of a kind of protein, CES2, needed to activate a common cancer drug, PPD. Orlistat has also been associated with gastrointestinal issues, as well as liver toxicity ¹⁵⁷.

Diet pills may decrease users’ vitamin D levels. Researchers found that adolescent participants’ vitamin D levels decreased after one month of taking orlistat, despite participants also taking a multivitamin daily. Vitamin D is important for bone health, cell growth, and immune function ¹⁵⁸.

Diet pills could be abused by people with eating disorders. In anticipation of the release of alli (the brand of orlistat now available over the counter), researchers expressed concerns regarding the potential for alli to be abused by people with eating disorders. Their concerns are based on documentation of adult and adolescent eating disorder patients frequently abusing supplements sold for weight loss, as well as the possibility that alli’s FDA approval would make it more appealing than other products sold for weight loss ¹⁵⁹.

Summary

The evidence supporting the use of dietary supplements to reduce body weight and stimulate weight loss is inconclusive and unconvincing, and the cost of these products can be considerable. The best way to lose weight and keep it off is to follow a sensible approach that incorporates a healthy eating plan, reduced caloric intake, and moderate physical activity under the guidance of a heath care provider. For some individuals with a high BMI who have additional health risks, physicians may prescribe adjunctive treatments, including FDA-approved prescription medications or bariatric surgery, in addition to lifestyle modifications. Lifestyle changes that promote weight loss might also improve mood and energy levels and lower the risk of heart disease, diabetes, and some cancers.

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158. McDuffie JR, Calis KA, Booth SL, Uwaifo GI, Yanovski, JA. Effects of orlistat on fat-soluble vitamins in obese adolescents. 2002;22(7):814-822.
159. Cumella EJ, Hahn J, Woods BK. Weighing Alli’s Impact: Eating disorder patients might be tempted to abuse the first FDA-approved nonprescription diet pill. Behavioral Healthcare. 2007;27:32–34.

What is Hoodia ?

Hoodia (hoodia gordonii) also called Kalahari cactus or Xhoba (Masson) — is a flowering, cactus-like plant that grows in the Kalahari Desert indigenous to the arid regions of South Africa, Botswana, and Namibia in Africa ¹. Historically, the San Bushmen are said to chew the plant to help stave off hunger or to suppress appetite and thirst during long hunts. However, it may be more accurate to say that Hoodia is a food source and was used mostly to quench thirst. ². An initial exploratory research with several species of Hoodia showed that H. gordonii contained steroid glycosides have appetite suppressant properties that decreased food intakes and body weights in lab rats ³. The research indicated the efficacy of Hoodia gordonii extract-12 and Hoodia gordonii extract-20, which are 2 major steroid glycosides present in Hoodia gordonii, that pointed to these steroid glycosides as potential lead appetite-suppressing components of H. gordonii. A safety study with a 13-wk repeated administration of Hoodia gordonii extract4 (which contained 79.3% steroid glycosides) also showed that Hoodia gordonii extract induced significant dose-dependent reductions in food intakes and body weights in laboratory rats (SL Nicholson, A Orsi, G Salmon, CW Tam, and CL Ward, unpublished observations, 2007).

From this limited but supportive research evidence and very substantial anecdotal literature, extracts of Hoodia gordonii have become widely promoted as food supplements with putative weight-management properties. This development has arisen despite a lack of published evidence for efficacy and safety from randomized placebo-controlled human clinical trials that used well-characterized material and known dose-exposures to Hoodia gordonii ⁴.

Today, hoodia dietary supplements are used as an appetite suppressant for weight loss.

Dried extracts of stems and roots of Hoodia are used to make powders, capsules, chewable tablets and liquid preparations for making teas. Some hoodia products also contain other herbs or minerals, such as green tea or chromium. Because it is sold as a dietary supplement, hoodia escapes the level of scrutiny the FDA gives prescription drugs and medications sold over the counter.

Widely sold over the Internet and in health food and discount stores, Hoodia gordonii is typically offered in capsules or tablets, but is also available in milk chocolate chews. A 30-day supply often costs $35 and up.

We know very little about hoodia because only one study of this herb has been done in people. No conclusive evidence to support the claim of appetite suppression.

Little is known about the safety of hoodia. However, the one completed study in people raises concerns ⁴. In that study, participants taking hoodia had more side effects than those taking placebos, including nausea, vomiting, dizziness, and odd skin sensations; they also had increases in blood pressure and undesirable changes in some blood tests.

Still, some dietary supplement manufacturers market hoodia products as a way to suppress appetite and aid in weight loss. The Federal Trade Commission has warned manufacturers to stop making these unsubstantiated and misleading claims about hoodia and weight loss.

In addition, the quality of hoodia products varies widely. In some cases, hoodia products have been found to contain unidentified ingredients that could be harmful.

Remember, just because an herbal supplement may be natural doesn’t mean it is safe. Steer clear of products that make unproven claims. And always check with your doctor before taking supplements.

Hoodia and Weight Loss

Extracts from Hoodia gordonii have been shown to decrease food intakes and body weights in animals and were proposed as a food supplement or ingredient for weight management ⁴. The Hoodia species with purported appetite-suppressing properties is Hoodia gordonii. In the 1990s, researchers isolated an extract of the plant called P57, an oxypregnane steroidal glycoside, is the only reported active constituent from this plant as an appetite suppressant, which is thought to stimulate feelings of satiety in the brain ⁵, ⁶.

In a very small randomised study involving 49 healthy overweight women aged 18–50 yrs ⁴. The women were divided into two groups, 25 women were given the Hoodia gordonii extract 2 servings/day of 1110 mg Hoodia gordonii extract in a raspberry-flavored yogurt drink and the other 24 women got placebo formulated in a yogurt drink, to be taken 1 hour before breakfast and dinner for 15 days ⁴. The women in both groups could eat whatever they like without any restriction. After 15 days there were no difference between the women in terms of the amount of food intakes and body weights. However, the women taking the Hoodia gordonii extract had episodes of nausea, emesis (vomiting) and disturbances of skin sensation ⁴. Moreover, the consumption of HgPE for 15 d appeared to be associated with significant adverse changes in some vital signs and laboratory parameters – blood pressure, pulse, heart rate, bilirubin, and alkaline phosphatase showed significant increases in the Hoodia gordonii extract group ⁴.

In a literature review, the reviewer did not find any published, peer-reviewed randomized controlled trials examining efficacy of Hoodia. In addition, the reviewer found literature that suggests some commercial products may not actually contain Hoodia at all ⁷. It’s not known if this is still a problem for hoodia supplements sold today.

Hoodia Side Effects

We know very little about hoodia because only one study of this herb has been done in people.

In the one small study of hoodia in people, overweight women who took hoodia for 15 days didn’t lose more weight than those who took a placebo ⁴.

Little is known about the safety of hoodia ². However, the one completed study in people raises concerns. In that study, participants taking hoodia had more side effects than those taking placebos, including nausea, vomiting, dizziness, and odd skin sensations; they also had increases in blood pressure and undesirable changes in some blood tests.

Hepatotoxicity (Liver Toxicity)

Hoodia has been in use as a weight loss agent for several years and has not been convincingly linked to instances of acute liver injury. In a small controlled trial, serum alkaline phosphatase [8-17 U/L] and bilirubin [0.2-0.6 mg/dL], but not ALT levels, were slightly higher in patients on Hoodia compared to placebo, but no patient developed symptoms or clinically apparent liver injury ⁸.

Whether hoodia interacts with medicines or other supplements is not known.

References

1. Bruyns P. Stapeliads of Southern Africa and Madagascar. Hatfield, South Africa: Umdaus Press, 2005.
2. National Center for Complementary and Integrative Health. Hoodia. https://nccih.nih.gov/health/hoodia
3. van Heerden FR, Marthinus HR, Maharaj VJ, Vleggaar R, Senabe JV, Gunning PJ. An appetite suppressant from Hoodia species. Phytochemistry 2007;68:2545–53. https://www.ncbi.nlm.nih.gov/pubmed/17603088?dopt=Abstract
4. Blom WAM, Abrahamse SL, Bradford R, et al. Effects of 15-d repeated consumption of Hoodia gordonii purified extract on safety, ad libitum energy intake, and body weight in healthy, overweight women: a randomized controlled trial. American Journal of Clinical Nutrition. 2011;94(5):1171-1181. http://ajcn.nutrition.org/content/94/5/1171.long
5. Preuss HG, Rao CV, Garis R, et al. An overview if the safety and efficacy of a novel, natural hydroxycitric acid extract (HCA-SX) for weight management. JMed. 2004;35:33-48.
6. Avula B, Wang YH, Pawar RS, Shukla YJ, Schaneberg B, Khan IA. Determination of the appetite suppressant P57 in Hoodia gordonii plant extracts and dietary supplements by liquid chromatography/electrospray ionization mass spectrometry (LC-MSD-TOF) and LC-UV methods. J AOAC Int 2006;89:606–11. https://www.ncbi.nlm.nih.gov/pubmed/16792058?dopt=Abstract
7. J Clin Pharm Ther. 2010 Oct;35(5):609-12. doi: 10.1111/j.1365-2710.2009.01116.x. Case report. Efficacy of Hoodia for weight loss: is there evidence to support the efficacy claims ? http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2710.2009.01116.x/abstract;jsessionid=ADA538F21D99256D9FB968A8F34CE7AD.f04t02
8. National Institutes of Health, National Library of Medicine. HOODIA. https://livertox.nlm.nih.gov/Hoodia.htm

What is Acai Berry

The acai berry is a grapelike fruit harvested from acai palm trees, which are native to the rainforests of Central and South America. The acai fruit has long been an important food source for indigenous peoples of the Amazon region.

Acai berry is the a reddish-purple fruit. Acai is widely consumed as an edible fruit or juice and is also available as a dietary supplement (acai products are available as juices, powders, tablets, and capsules).

There is no definitive evidence that acai has any special health benefits.

Acai berries are widely touted as a so-called superfood, with proponents claiming that they are helpful for a variety of health concerns, including arthritis, weight loss, high cholesterol, erectile dysfunction, skin appearance, detoxification and general health.

Acai berries contain antioxidants, fiber and heart-healthy fats. They may have more antioxidant content than other commonly eaten berries, such as cranberries, blueberries and strawberries. But, research so far on acai berries is limited, and claims about the health benefits of acai berry haven’t been proved.

The acai berry’s anthocyanin content gives it its rich purple color. Anthocyanins are powerful antioxidants that may protect the body against cancer, inflammation, diabetes, aging, neurological diseases, and bacterial infections.

Keep in mind that many fruits besides acai berries provide antioxidants and other nutrients that are important to your health – and you can get similarly antioxidant-rich whole fruits and vegetables for a fraction of the cost of acai berry and in their natural form (without extra sugar or calories). Blueberries, blackberries, and raspberries are more economical choices that deliver similar health benefits

However, if you’d like to try acai, check your local health food or gourmet stores — acai berry can be consumed raw, in tablet form, in beverages such as juice, smoothies or energy drinks, or in other food products such as jelly or ice cream.

Acai berry is safe to consume, as long as you’re not allergic to the fruit. But, use caution when consuming products made with acai that may have other ingredients, such as caffeine.

If you’re taking amounts of acai higher than you’d normally eat as food, such as in dietary supplements, be sure to check with your doctor. This is especially important for people taking medications for high cholesterol or diabetes, and for people with kidney disease, as large amounts of acai might affect the management of these conditions.

It’s also important to let your doctor know that you’ve been eating acai berries if you’re scheduled to have a magnetic resonance imaging (MRI) test. Very large doses of acai might affect the results of MRI scans.

Can acai berries boost weight loss ?

Some weight loss products tout acai, but few studies have tested whether acai promotes weight loss.

Most dietary supplements sold for rapid weight loss, such as acai and hoodia, aren’t effective at keeping weight off in the long term.(Source ¹).

Researchers who investigated the safety profile of an acai-fortified juice in rats observed that there were no body weight changes in animals given the juice compared with animals that didn’t receive it.

Currently there is no high-quality, independent studies have been published about the efficacy of acai supplements in promoting rapid weight loss. (Source ²).

• There is no scientific evidence based on clinical studies to support the use of acai supplements for any health-related purpose.
• In a laboratory study examining the safety profile of an acai-fortified juice found no changes in body weight compared with controls.

Many people who want to lose weight turn to unproven dietary supplements. These are sometimes called “fat burners” or appetite suppressants. But before you try them, remember two things:

⇒ These products make all sorts of claims for which they are not accountable.

⇒ ‘Natural’ doesn’t mean ‘safe.’

These products are not tested for safety by the FDA or anyone else. And they can have harmful side effects. (Source ¹).

Therefore the Federal Trade Commission has taken action against companies that marketed acai weight loss products in allegedly deceptive ways.

There’s no doubt that berries and other fruits are a key part of any healthy diet. The jury’s still out on whether there is something special about acai’s ability to help shed excess pounds.

Acai Berry Safety and Side Effects

There is little reliable information about the safety of acai as a supplement. It is widely consumed as an edible fruit or as a juice.
People who are allergic to acai or to plants in the Arecaceae (palm) family should not consume acai.

Consuming acai might affect MRI test results. If you use acai products and are scheduled for an MRI, check with your health care provider.

Conclusion:

There’s no definitive scientific evidence based on studies in people to support the use of acai for any health-related purpose.

No independent studies have been published in peer-reviewed journals that substantiate claims that acai alone promotes rapid weight loss.

There is little reliable information about the safety of acai as a supplement. It is widely consumed as an edible fruit or as a juice.

Most dietary supplements sold for rapid weight loss, such as acai and hoodia, aren’t effective at keeping weight off in the long term.(Source ¹).

A preliminary study suggested that eating acai fruit pulp might reduce blood sugar and cholesterol levels in overweight people.

Laboratory studies have focused on acai’s potential antioxidant properties, and a juice blend with acai as the main ingredient has been shown to have an antioxidant effect in people. (Antioxidants are substances that may protect cells against certain types of damage.) Acai berries have no known health benefit that’s different from similar fruits, e.g. blueberries, blackberries, and raspberries.

References

1. American Heart Association’s Heart Insight Magazine Spring 2015 – Dietary Supplements – http://heartinsight.heart.org/Spring-2015/Dietary-Supplements/
2. National Center for Complementary and Integrative Health – Weight Control and Complementary and Integrative Approaches:
   What the Science Says at https://nccih.nih.gov/health/providers/digest/weightloss-science

Garcinia Cambogia

Garcinia cambogia, a tropical fruit also known as the Malabar tamarind, brindle berry or garcinia is a popular weight-loss supplement. Garcinia cambogia is made into a tea, capsules, extracts, tablets, and lotion.

Garcinia cambogia (Malabar tamarind) is native to India and Southeast Asia. The rind of its fruit is used to flavor fish curries and preserve food. The rind contains a chemical called hydroxycitric acid, which has been studied for its effect on appetite. Garcinia cambogia supplements with hydroxycitric acid are marketed for weight loss.

Garcinia cambogia has also been used as a dietary supplement for weight loss, rheumatism, intestinal problems, and other conditions.

Hydroxycitric acid (HCA) is the active ingredient found in the fruit of the Garcinia cambogia plant ¹. It is believed that hydroxycitric acid aids in weight loss by inhibiting lipogenesis by inhibiting the adenosine triphosphate (ATP)-citrate-lyase enzyme which is responsible for converting citrate to acetyl-coenzyme A and ultimately fatty acid synthesis. It is also theorized that HCA may improve exercise endurance by increasing lipid oxidation and decreasing carbohydrate metabolism and stimulate appetite suppression ², ¹.

And if you’re about to take what you think of as “natural” dietary supplements, such as Garcinia cambogia, you should be aware that FDA has found some of these products also contain hidden active ingredients contained in prescription drugs ³.

Garcinia Cambogia (Hydroxycitric Acid) in the treatment of Obesity

In a small randomized, double-blind, placebo-controlled trial to measure the effects of Garcinia Cambogia (Hydroxycitric Acid) on body weight change and fat mass ⁴. The 135 participants (19 men and 116 women) with an average BMI of 32 kg/m2 were randomized to receive 3000 mg of Garcinia cambogia (1500 mg of Hydroxycitric Acid) per day or placebo along with a high fiber, low-calorie diet for 12 weeks. The placebo group lost 4.1 kg, and the Garcinia cambogia group lost 3.2 kg. There were no significant differences in estimated percentage of body fat mass loss between treatment groups, and the fraction of subject weight loss as fat was not influenced by treatment group. In addition, the placebo group demonstrated a decrease in percent body fat mass of 2.16%, and the Hydroxycitric Acid group demonstrated a 1.44% decrease. The most commonly reported adverse events were headache, upper respiratory tract symptoms, and gastrointestinal symptoms. The study authors concluded that Garcinia cambogia failed to produce significant weight loss and fat mass loss beyond that observed with placebo ⁵.

A double-blind, placebo-controlled parallel group study performed by Mattes and Bormann ⁶ enrolled 89 mildly overweight females to evaluate Garcinia cambogia (Hydroxycitric Acid) on weight loss and appetite suppression. The participants were randomized to receive 2.4 grams of Garcinia cambogia (1.2 grams of Hydroxycitric Acid) or placebo per day, in addition to a low calorie diet. At the end of 12 weeks, it was noted that the Hydroxycitric Acid group lost significantly more weight than the placebo group (3.7 kg versus 2.4 kg). There were no changes on appetitive variables ⁶.

In another small double-blind, randomized, placebo-controlled, parallel-group designed study ⁷. 44 subjects aged 20 to 65 years with a visceral fat area >90 cm2 were enrolled. Subjects were randomly assigned to receive treatment for 12 weeks with G cambogia (containing 1000 mg of Hydroxycitric Acid per day) or placebo. At the end of the treatment period, both groups were administered placebo for 4 weeks to assess any rebound effect. Each subject underwent a computed tomography scan at the umbilical level at −2, 0, 12, and 16 weeks.

The conclusion from that study ⁷ showed that Garcinia cambogia reduced abdominal fat accumulation in subjects, regardless of sex, who had the visceral fat accumulation type of obesity. It is therefore expected that G cambogia may be useful for the prevention and reduction of accumulation of visceral fat.

However in another study ⁸ involving 135 subjects who were randomized to either active hydroxycitric acid (n = 66) or placebo (n = 69), there were no significant differences in estimated percentage of body fat mass loss between treatment groups and the fraction of subject weight loss as fat was not influenced by treatment group. The conclusion was Garcinia cambogia failed to produce significant weight loss and fat mass loss beyond that observed with placebo.

Although several studies have found that the administration of Garcinia cambogia extracts is associated with body weight and fat loss in both experimental animals and humans, we should be cautious when interpreting the results as other randomized, placebo-controlled clinical trials have not reported the same outcomes. Furthermore, most studies in humans have been conducted on small samples and mainly in the short term. None of them have shown whether these effects persist beyond 12 weeks of intervention. Therefore, there is still little evidence to support the potential effectiveness and long-term benefits of Garcinia cambogia extracts.

While Garcinia cambogia appears to be well tolerated, there is limited data with regards to its efficacy. The data that is available, however, does not demonstrate significant weight loss. Therefore, Garcinia cambogia or Hydroxycitric Acid is not recommended at this time.

How Much Do We Know About Garcinia Cambogia ?

Garcinia cambogia has been studied for weight loss, but there aren’t a lot of recent, reliable studies on its effectiveness.

• There’s no convincing evidence that garcinia cambogia will help you lose weight or control cholesterol.
• In a very small study, women who were overweight were given garcinia cambogia extract or a placebo for 60 days. Triglyceride levels of the participants getting garcinia cambogia decreased by almost one-third. Triglycerides are a type of fat in blood and high levels may raise a person’s risk of developing heart disease. The participants’ HDL (the “good” cholesterol), LDL (the “bad” cholesterol), total cholesterol, and body weight didn’t change.
• In another study, people who were overweight were given either garcinia cambogia extract, soy leaf extract, or a placebo. After 10 weeks, none of the supplements promoted weight loss or lowered total cholesterol.

What Do We Know About Safety ?

Taking garcinia cambogia for short periods (12 weeks or less) appears safe for most people ⁹.

In an animal study to investigate the effect of long-term Garcinia cambogia supplementation on adipogenesis and obesity-related metabolic changes, such as glucose intolerance and hepatic steatosis, in mice fed a high fat diet. The study also examined the effect of Garcinia cambogia on liver dysfunction, collagen accumulation, inflammation and oxidative stress on obesity-prone mice that were fed a high-fat diet (45 kcal% fat) with or without Garcinia cambogia for 16 wk. . (source ¹⁰). The result of that study was Garcinia cambogia protects against high-fat diet-induced obesity by modulating adipose fatty acid synthesis and β-oxidation but induces hepatic fibrosis, inflammation and oxidative stress. Furthermore, some studies have reported the potential for hepatotoxicity of “Hydroxycut”, a formulation that contains GC among other ingredients ¹¹, ¹².

Possible Side Effects

When you take garcinia cambogia, you might get:

• Dizziness
• Dry mouth
• Headache
• Upset stomach or diarrhea

You definitely don’t want to use it when you’re pregnant or nursing, or if you have kidney or liver problems.

References

1. Natural Medicines Comprehensive Database. Stockton, Calif, USA: Therapeutic Research Faculty; Garcinia cambogia.
2. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C. JAMA. 1998 Nov 11; 280(18):1596-600. https://www.ncbi.nlm.nih.gov/pubmed/9820262/
3. U.S. Food and Drug Administration – Beware of Products Promising Miracle Weight Loss – https://www.fda.gov/forconsumers/consumerupdates/ucm246742.htm
4. Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C. Garcinia cambogia (Hydroxycitric Acid) as a Potential Antiobesity AgentA Randomized Controlled Trial. JAMA. 1998;280(18):1596-1600. doi:10.1001/jama.280.18.1596. http://jamanetwork.com/journals/jama/fullarticle/188147
5. Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C. Garcinia cambogia (Hydroxycitric Acid) as a Potential Antiobesity Agent A Randomized Controlled Trial. JAMA. 1998;280(18):1596-1600. doi:10.1001/jama.280.18.1596. http://jamanetwork.com/journals/jama/fullarticle/188147
6. Effects of hydroxycitric acid on appetitive variables. Mattes RD, Bormann L. Physiol Behav. 2000 Oct 1-15; 71(1-2):87-94. https://www.ncbi.nlm.nih.gov/pubmed/11134690/
7. Curr Ther Res Clin Exp. 2003 Sep; 64(8): 551–567. Effects of garcinia cambogia (Hydroxycitric Acid) on visceral fat accumulation: a double-blind, randomized, placebo-controlled trial – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4053034/
8. JAMA. 1998 Nov 11;280(18):1596-600. – Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. – https://www.ncbi.nlm.nih.gov/pubmed/9820262
9. Crit Rev Food Sci Nutr. 2012;52(7):585-94. – Evaluation of the safety and efficacy of hydroxycitric acid or Garcinia cambogia extracts in humans. – https://www.ncbi.nlm.nih.gov/pubmed/22530711
10. World J Gastroenterol. 2013 Aug 7; 19(29): 4689–4701. Garcinia Cambogia attenuates diet-induced adiposity but exacerbates hepatic collagen accumulation and inflammation – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732841/
11. Stevens T, Qadri A, Zein NN. Two patients with acute liver injury associated with use of the herbal weight-loss supplement hydroxycut. Ann Intern Med. 2005;142:477–478. – https://www.ncbi.nlm.nih.gov/pubmed/15767636
12. Dara L, Hewett J, Lim JK. Hydroxycut hepatotoxicity: a case series and review of liver toxicity from herbal weight loss supplements. World J Gastroenterol. 2008;14:6999–7004. – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773866/