Ephedrine and Caffeine Combination

Elizabeth Crum

Table of Contents

What does adding stimulants to diet pills do?

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Claims made about Ephedrine/Caffeine combination

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1.enhances thermogenesis

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2.preserves lean body mass

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3.improves weight loss

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Ephedrine/Caffeine Products

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Opponents

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Side Effects

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Conclusion

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Resources

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What does adding stimulants to diet pills do?

            It is believed that adding caffeine to diet pills may increase weight loss (http://www.vitamins.com/encyclopedia/Concern/Weight_Loss.htm and http://www.mothernature.com/ency/Concern/Weight_Loss.asp). Many diet pills contain caffeine or guaranine, which is found in the herb guarana and is almost identical to caffeine.  Caffeine acts as a stimulant of the central nervous system.  The stimulant also increases the body’s metabolism and is a mild diuretic.  It is rare to find caffeine in a diet pill without the combination of ephedrine.  The combination of the two stimulants is more effective than the use of them individually.

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Claims made about the Ephedrine/Caffeine Combination in diet pills:

It Enhances Thermogenesis

            Ephedrine and caffeine work individually and as a combination when ingested into the body (http://www.endureplus.com/caffeine_ephedrine.htm).  Caffeine has properties that stimulate the central nervous system and the energy metabolism in the peripheral tissues. These stimulations can cause four other reactions: adenosine receptor blockage, improved neuromuscular transmission, increased muscle contractility, and increased adrenalin levels.  Ephedrine also stimulates parts of the central nervous system and the peripheral tissues known as the adrenergic receptors.  Essentially ephedrine can act like adrenalin in the body so a person’s energy level increases also.  The effect of the combination of ephedrine and caffeine is best described as promoting thermogenesis (http://www.lef.org/magazine/mag98/dec98_heat.html).  Thermogenesis is the “chemical production of heat within the body to promote the oxidation of body fat.”  The ingestion of ephedrine and caffeine promotes weight loss because energy expediture increases and the intake of food decreases.  In Larry Hobbs’s Ephedrine and Caffeine: The Ideal Diet Pill?, he lists six reasons why ephedrine and caffeine are a remarkable combination (http://www.ephedra.demon.nl/stories/artik001.htm or http://www.bennrye.com/articles/articles2.htmlorhttp://www.lowcarbnexus.com/ec.htm):

1.      Increases fat loss.

2.      Maintains muscle mass.

3.      Prevents the fall of HDL cholesterol during weight loss.

4.      Increases insulin sensitivity.

5.      Reduces lipogenesis.

6.      Is very safe (despite recent sensationalist news reports to the contrary).

Larry Hobbs’s article is posted on three different internet sites and is backed with many references.

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It Preserves A Lean Body Mass

            Larry Hobbs discusses three experiments in his article. The first experiment is done to prove that a diet pill with the ephedrine-caffeine combination is the ideal diet pill because it increases fat loss and simultaneously maintains muscle mass. The study shows that dieting women given the ephedrine-caffeine diet pill lost twice as much fat as the women receiving the placebo.  The two groups had similar total weight loss.  The diet pill group lost 22.2 pounds while the placebo group lost 18.5 pounds.  The difference is that the placebo group lost three-quarters more muscle than the ephedrine-caffeine (EC) group. Another study proves that the EC combination is more effective than the  Redux diet pill.  The EC lost 29% more body weight than the Redux group.  The third study is done to show that ephedrine and caffeine are not effective if not combined.  The test is done on a group of people with a 1,000 calorie per day diet.  The two groups that were taking ephedrine and caffeine individually did not have an enhanced weight loss.  After six months, the EC combination group lost 6.6 to 10.1 pounds.  Although the explanations of these experiments are found on a website with many references, they are not very detailed.  Another problem is that Larry Hobbs does not footnote throughout his article so it is misleading as to where the information is coming from and if the information has actually been proven true.

            In a medical journal called Metabolism, a study on the effect of ephedrine/caffeine mixture on energy expenditure and body composition in obese women is explained.  The study was a double-blinded placebo-controlled trial.  A third party formed two groups with 16 healthy obese women: an ephedrine/caffeine group and a placebo group.  Both groups were also put on a 4.2-MJ/d diet and watched for eight weeks receiving their drug three times a day.  All the patients had their body composition and 24-hour energy expenditure measured three times throughout the study: (1) during pre-treatment on a weight maintenance diet (2) at the first day of treatment with the diet and drug (3) at the last day of treatment which would be the 56th day.  At the end of the study weight loss was not different in the two groups, but the E+C group lost 4.5 kg more body fat and 2.8 kg less fat-free mass.  The E+C group also had a smaller decrease in energy expenditure.  It was 7% at Day 1 and 8% at Day 56 compared to 10% and 13% in the placebo group.  This shows that the promotion of fat loss and the preservation of fat-free body mass can be obtained pharmacologically during weight loss. (Astrup, Buemann, Christensen, Toubro, Torbek, Victor, Quaade, 1992)

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It Improves Weight Loss

            Another website gives detailed description of an experiment that was performed on monkeys (http://www.lef.org/magazine/mag98/dec98_abs.html).  Researchers wanted to test the hypothesis that ephedrine and caffeine promote weight loss by increasing energy expenditure and decreasing food intake.  The test is done on two different groups of monkeys: 6 lean monkeys which means they have 4-9% body fat and 6 mildly-to-moderately obese monkeys which means they have 13-44% body fat.  The monkeys are watched during a 6-week control period, an 8-week drug treatment period, and then a 7-week placebo treatment period.  During the second period,  the monkeys are given 6 mg of ephedrine and 50 mg of caffeine three times a day by way of mouth.  At the end of each period, a glucose tolerance test is performed and the energy expenditure is measured so that the body composition can be determined.  The results show that there is a decrease in the body weight of the obese monkeys and 19% of the decrease is in body fat.  Even though the food intake is only decreased in the obese monkeys, the lean monkeys also have a decrease in body fat. This experiment proves that the ephedrine-caffeine combination can enhance a small weight loss in individuals that are already lean without of change in their diet.  This experiment is more informative than the ones that Larry Hobbs describes.  The details make it easier for a person to understand how and to what extent ephedrine and caffeine affect a living creature.  An in depth description of this study can be found in the American Journal of Clinical Nutrition.  The study was very precise and the results were well charted. (Ramsey, Colman, Swick, Kemnitz, 1998)

Comparison Of Control Period Variables In The Obese and Lean Groups

Of Rheus Monkeys

Values greater in the obese than in the lean animals (P<0.10)

Values not significantly different between obese and lean animals (P>0.10)

Values lower in obese than in lean animals (P<0.10)

Body Weight (0.003)

Lean Tissue Mass (0.053)

Fat Mass (0.006)

Leptin (0.004)

Basal insulin (0.033)

Basal glucose (0.023)

Morning Energy Expenditure (0.179)

Afternoon Energy Expenditure (0.670)

Evening Energy Expenditure (0.236)

24-hour Energy Expenditure (0.999)

Triiodothyronine (0.978)

Glucose Effectiveness (0.145)

Glucose Disappearance Rate (0.120)

Acute Insulin Response To Glucose (0.573)

2nd-Phase Insulin Response To Glucose (0.455)

Insulin Response To Tolbutamide (0.111)

Food Intake (0.015)

Insulin Sensitivity (0.047)

Disposition Index (0.068)

 

            To better understand the EC combination, there is also a major study that is performed on actual human beings that is described in great detail (http://www.lef.org/magazine/mag98/dec98_heat.html).  This particular study compares the weight loss effects in the EC combination diet pill and the Dexfenfluramine (Redux) diet pill, which has now been banished because it contains a compound associated with a rare and serious defect in the heart valve.   The double-blind trial is 15-weeks long and consists of 103 patients that are 20-80% overweight.  The patients are randomly divided into two groups.  One group received 15 mg of Redux twice a day, and the other group received a combination of 20 mg of ephedrine and 200 mg of caffeine three times a day.  After the treatment ended, the EC combination group lost an average of 18 pounds per person while the Redux group lost an average of 15 pounds per person. Both groups had a similar reduction in systolic and diastolic blood pressure.  43% of the patients in the Redux and 54% of the patients in the EC combination group complained about side effects.  The EC group had more central nervous system complaints like agitation while the Redux group complained of gastrointestinal symptoms.  A positive aspect is that the adverse effects did decrease after the first month of dosage.  An in depth description of this study can be found in the International Journal of Obesity.  New data has proven that this ephedrine/caffeine combination is a thermogenic and anorectic agent that is both effect and safe for long periods of treatment.  This study is different than the majority of studies done on the ephedrine/caffeine combination because it was compared to another active treatment.  Also, the study was not performed in an obesity unit; therefore, the study was done in a clinical situation closer to one where the drugs would normally be prescribed. (Breum, Pedersen, Ahlostrom, Moller, 1994)

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Products containing the Ephedrine-Caffeine combination

            A whole website is devoted to a review of nutritional supplements (http://www.supplementwatch.com/reviews/weight_loss_products.html).  This website has been set up by a Scientific Advisory Council, which consists of scientists from all over the United States (http://www.supplementwatch.com/about/science_board.html).  Nine of the eleven scientists on the council have their Ph.D.  They  started the site called “The Supplement Watch” in 1999 in response to the confusion that many people have about dietary and nutritional supplements.  There is a search provided so that it is easy to locate any supplement.  All the products are rated on a 100 point scale. There are five different categories each worth 20 points each: Claims, Theory, Scientific Support, Safety, and Value.  The product can then be placed in one of five categories depending on how many points it receives: 100-90points = Try it!, 90-80 = Recommended, 80-70 = Promising, 70-60 = Hold Off, and less than 60 = Don’t Waste Your Money! The Ephedrine-Caffeine combination products given a review are TwinLab Ripped Fuel, TwinLab Diet Fuel, Met-Rx Thermicore, Muscletech’s Hydroxycut, Xenadrine RFA-1 by Cytodyne Technologies, Metacuts by Metaform, Zyladex Plus Medlab, Bio-energetic Weight  Control Trek Alliance, and Metabolife356.  With the exception of Zyladex Plus Medlab, which received low ratings on all five sections, all the other supplements scored fairly high on the claims, theory, and scientific support sections.  These products are valid.  The manufacturers just forget to tell the consumers the adverse effects of taking the supplements.  Most of the directions for these EC diet pills recommend a dosage of ephedrine that the Food and Drug Administration would consider too much for a person to consume in one day.  FDA advises a person not to consume more than 24 mg a day or more than 8 mg at one time.  Many different side affects can occur from taking these pills: nervousness, headache, insomnia, heart palpitations, and dizziness.  Ephedrine and caffeine could also have an effect on blood pressure and blood sugar.  People with high blood pressure, a history of cardiovascular or thyroid disease, diabetes, prostate problems or are taking prescription medicine are advised not to take these products.

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Opponents of Caffeine and its effects on weight loss

Another reliable website is provided by the Mayo Clinic (http://www.mayo.edu/)  More than 2,000 physicians and 35,000 allied health staff work in the Mayo system, treating nearly a half a million patients annually.  The site provides a question and answer section where the effects of caffeine are directly addressed (http://www.mayohealth.org/mayo/askdiet/htm/new/qd990324.htm).  The Mayo Clinic does agree that larger doses of ephedrine and caffeine or other stimulants may have slightly enhance weight loss in individuals that exercise and maintain a low fat diet, but the adverse effects are far greater than the small enhancement of weight loss.  Caffeine does stimulate the nervous system, which then increases  heart rate, but it does not increase metabolic rate or the ability for the body to burn more calories than usual.  The dosage in the diet pills is said to be equal to 6 strong cups of coffee a day.  This high level of caffeine will cause “jitters, irritability, insomnia, and elevated blood pressure.”  The Mayo Clinic also agrees that caffeine does suppress appetite, but this suppressive effect does not last long enough to lead to a large amount of weight loss.  Caffeine is also a diuretic, which seems good because excess water would leave the body via urine, but the problem is that even though the body weight is decreasing, the body fat is not.  Mayo claims that there are not any studies that show a significant and permanent weight loss from caffeine.

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Side Effects of Taking An Ephedrine/Caffeine Combination Diet Pill

A double blind trial was done to compare the effects and safety of an ephedrine/caffeine compound to ephedrine, caffeine, and placebo individually in obese people.  The randomized study was done on 180 obese patients.  All the patients were treated by a diet and then they received one of four pills: an ephedrine/caffeine combination (20mg/200mg), ephedrine (20mg), caffeine (200mg), or a placebo three times a day for 24 weeks.  The results of the side effects were charted so that they could be compared.

NUMBER OF PATIENTS

 

E+C

EPHEDRINE

CAFFEINE

PLACEBO

DIZZINESS

5

2

5

1

HEADACHE

2

2

3

0

TREMOR

5

4

1

0

DEPRESSED

MOOD

1

2

2

0

EUPHORIA

2

1

2

0

INSOMNIA

9

8

3

3

DRY MOUTH

0

3

0

0

POSTURAL HYPOTENSION

2

2

1

1

PALPITATION

2

1

0

0

TACHYCARDIA

2

2

0

0

CONSTIPATION

0

1

0

2

 

 

                                                                        SIDE EFFECTS

                                        

NUMBER OF SYMPTOMS

 

 

E+C

EHPEDRINE

CAFFEINE

PLACEBO

4

27

25

22

5

8

3

2

2

3

12

5

5

1

1

16

3

1

1

1

20

2

4

1

1

24

4

3

5

2

 

 

 

TIME OF REPORT (WEEK)


The only time that more symptoms were reported in the E+C, E, and C than in the placebo was at week 4.  The side effects were present in all three non-placebo studies at the beginning of the study, but by the eighth week they all reached placebo level.  Although there were several withdrawals, they were distributed equally among the three groups so the trial was completed with 141 patients. (Astrup, Breum, Toubro, Hein, Quaade, 1992)

            Side effects were also recorded during the study that compared ephedrine/caffeine combination with dexfenfluramine in the treatment of obesity. (Breum et al., 1994)

 

 

Dexfenfluramine

Ephedrine/Caffeine

CNS Side Effects

 

 

Dizziness

4

1

Headache

3

2

Twitching and Tremor

0

5

Insomnia

1

8

Agitation

0

3

Paraesthesia

3

0

Nausea

6

5

Thirst

5

1

Fatigue

3

1

Cardiovascular Side Effects

 

 

Palpitations

0

4

Gastro-intestinal Side Effects

 

 

Diarrhoea

6

0

Constipation

2

1

Other Side Effects

 

 

Dry Mouth

1

2

 

 

            Another trial found in The International Journal of Obesity, studies the effects of the ephedrine/caffeine combination.  This particular study describes a 24-week follow up trial of a prior 24-week double-blind placebo-controlled study comparing the E+C combination to using each of the drugs individually.  The first trial was stopped so that the withdrawal symptoms could be studied.  After the 2-week period of not taking the E+C combination, 99 patients out of 127 with continued with the follow up study.  These 99 patients were put back on the E+C combination and after another 24-week period there was a result of an additional 1.1 kg weight loss.  This study proves that the E+C combination is safe and effective in improving and maintaining weight loss. (Toubro, Astrup, Breum, Quaade, 1993)

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Conclusion

Different internet sites give different opinions about the effects of caffeine on weight loss.  It is common for the websites promoting caffeine use for weight loss to have quick shopping links to purchase these ephedrine-caffeine combination diet pills. For example, http://www.ephedra.demon.nl/stories/artik001.htm , http://www.bennrye.com/articles/articles2.html, http://www.lowcarbnexus.com/ec.htm, http://www.lef.org/magazine/mag98/dec98_abs.html, and http://www.lef.org/magazine/mag98/dec98_heat.html all supported the EC diet pill, but they do not mention the health risks that could occur form taking the supplement because they want the shopper to go to the online store  that is linked  to the website and purchase the supplements.  Other sites such as, http://www.mayohealth.org/mayo/askdiet/htm/new/qd990324.htm and http://www.supplementwatch.com/reviews/weight_loss_products.html, support the idea that EC diet pills can enhance weight loss, but they are not trying to sell anything.  These sites are produced to inform the public of nutritional facts and health risks involved with dietary supplements.  There is only one site that even mentions that caffeine could not be a permanent form of weight loss.  It is easy to lose weight, but keeping it off is the challenge.  How can caffeine be a solution for weight loss? A person’s body gets use to the substances ingested each day, especially something addicting like caffeine, so discontinuing the use of the pills could also leave the person feeling weak, tired, and fatigued easily.  If a person uses caffeine as a temporary appetite suppressor, the lost weight would be easy to gain back.

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Resources

Ahlstrom, F., Breum, L., Frimodt-Moller, J., & Pedersen, J.K. (1994). Comparison of an ephedrine/caffeine and dexfenfluramine in the treatment of obesity. A double-blind multi-centre trial in general practice. Internaltional Journal of Obesity. 18, 99-103.

American Society for Clinical Nutrition. (1998). Energy expenditure, body composition,  and glucose metabolism in lean and obese rhesus monkeys treated with ephedrine and caffeine. American Journal for Clinical Nutrition, 68:42-51.

Astrup, A., Breum, L., Hein, P., Toubro, S., & Quaade, F. (1992). The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo  in obese subjects on an energy restricted diet. A double blind trial. International Journal of Obesity. 16, 269-277.

Astrup, A., Breum, L., Toubro, S., & Quaade, F. (1993). The acute and chronic effects of ephedrine/caffeine mixtures on energy expediture and glucose metabolism in humans. International Journal of Obesity. 17 (Suppl. 3), S73-S77.

Astrup, A., Buemann, B., Christensen, N. J., Toubro, S., Torbek, G., Victor, O. J., & Quaade, F. (1992) The effect of ephedrine/caffeine mixture on energy  expenditure and body composition in obese women. Metabolism. 686-688.

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