The HCG Diet: Does It Work?

By David Kiefer, MD, Clinical Instructor, Family Medicine, University of Washington, Seattle; Clinical Assistant Professor of Medicine, University of Arizona, Tucson; Adjunct Faculty, Bastyr University, Seattle. Dr. Kiefer reports no financial relationships relevant to this field of study.

Welcome to the time of the new year's resolution. top of the list? Finally drop that 10-15 pounds and get back to the desired high school weight, or at least make an inroad into that recalcitrant body mass index (BMI) and associated health conditions such as hypertension, metabolic syndrome, or non-insulin-dependent diabetes. Weight loss is on a lot of people's minds,1 and is big business; people spend $40 billion yearly on weight loss programs and products.2 Also, about one-third of people in the United States will make a weight loss pledge for the new year. In addition, it may be a common question posed to one's health care provider: "I've tried everything. What else can I do?"

There are a plethora of diets and dietary supplements purported to be the magic bullet, though arguably one of the most trendy approaches is that encompassing human chorionic gonadotropin, or HCG (alternatively, in the scientific literature, it is abbreviated hCG). The 250,000 visits to the Dr. Oz discussion of this diet on YouTube may further support the popularity or, at the very least, the interest in this weight loss approach. Dr. Oz interviewed patients and doctors who attested to how they were able to lose 1 pound daily, on average, and were "never hungry" despite eating only 500 calories daily. The U.S. government recently became involved in this topic by expressing its opinion through an FDA and FTC lawsuit against some of the manufacturers of HCG products.3

To bring together the popular hype and medical research, this review will capture some of the results of clinical trials, comment on possible mechanisms of action, and discuss overall efficacy and safety of the HCG hormone and diet.

HCG Diet Components

The use of HCG in weight loss is often cited as originating with Dr. Albert T.W. Simeons in the 1950s.4 His protocol involved HCG injections (125 mcg intramuscularly 6 days per week for 6 weeks) and a variety of well-scripted dietary restrictions totaling only 500 calories daily. Since this initial use of HCG for weight loss, many variations on the protocol have surfaced, including the use of HCG drops (usually homeopathic) or a shorter treatment duration, for no less than 26 days (with 23 injections). Some companies support only pharmaceutical grade injections, while others criticize the unproven homeopathic drops favoring instead their particular formulation that includes a proprietary blend of amino acids. All have very convincing testimonials of success from health care practitioners and patients alike.

As mentioned in the January issue of Alternative Medicine Alert, HCG Diet Direct, HCG Platinum, and Nutri Fusion Systems are three of the companies listed in the FDA/FTC lawsuit.5 These and other products contain statements such as "Appetite Control and Detox," and "Weight Loss Formula," and may have homeopathic HCG (dosed from 6X-60X), with or without amino acids, herbal medicines, and other nutraceutical ingredients.

Despite the diversity of marketing and specific proprietary blends, the weight loss claims are similar: less hunger; preferential weight loss (20-40 pounds over 40 days) from thighs, abdomen, and hips; and mental support for the emotional aspect of dieting.4,6 One expert points out that the HCG component of these protocols may, in fact, be completely irrelevant, as most people on 500 calories daily would be expected to lose 1 pound daily with or without any supplemental nutrients or pharmaceuticals.7

Entire books and volumes of information on the Internet are dedicated to the specifics about the actual food part of the HCG protocol. Many current HCG diets are variations of the original Simeons protocol: any food intake for the first 2 days of injections, then begin the 500 calorie per day diet involving weighed quantities of protein and specific amounts of fruits, vegetables, and carbohydrates, but no fat, in two meals daily.8

Physiology of HCG

HCG is a hormone with numerous functions in the placenta, uterus, and fetus during pregnancy, including the promotion of progesterone production from the corpus luteum via binding to a combined hCG/LH receptor.9 There are two subunits (alpha and beta) in each HCG molecule, and four independent HCG variants (HCG, hyperglycosylated HCG, free beta subunit, and pituitary HCG); the beta subunit is conserved in these four variants, which are produced in different parts of the body and have different physiological effects.9 The common marketing claim that HCG "helps the developing fetus to get the necessary nutrients" seems to be the branch point from which a case is made for how the body mobilizes fat stores during the weight loss protocol. Most experts document, however, that HCG helps with fetal growth and development by promoting adequate blood vessel development in the placenta and by signaling mechanisms and receptors in fetal organs;9 there is no mention of a peripheral effect on maternal physiology that then leads to enhanced fetal nourishment.

One popular HCG website ventures into another hypothesized mechanism of action by stating that "The presence of HCG in the body signals the hypothalamus to release stored fats when low levels of calories are consumed."10 It is true that HCG receptors have been found in the central nervous system, including the hypothalamus, a possible etiology for nausea and vomiting of pregnancy rather than appetite control as proposed by the aforementioned website.9

One clinical trial allows some extrapolation to the realm of the hypothesized effect of HCG on weight loss. This double-blind, placebo-controlled clinical trial shed some light into how HCG might be affecting muscle and fat. Addressing suspected hypothalamic-pituitary dysfunction in older men, recombinant HCG was administered, with the hopes of helping with symptoms of testosterone deficiency, including energy, libido, and mood changes.11 Some of the thought for the use of HCG in this capacity comes from positive results for young men with gonadotropin deficiency or in idiopathic infertility, an FDA-approved indication for HCG therapy. In the above study, 250 mcg of HCG was self-administered subcutaneously twice weekly in 20 men for 3 months (and then the group was followed for 1 additional month), and numerous parameters were followed, including lean body mass and fat mass. In the treatment group, lean body mass and body weight increased compared to the placebo group (approximately 6 pounds and 2 pounds, respectively), and calculated fat mass, primarily at the mid-thigh, decreased approximately 4 pounds, all at the 3-month time point. Adverse effects were statistically similar between the two groups, but three people in the HCG group developed nipple tenderness (though not gynecomastia). This would seem to indicate that HCG may cause a change in fat vs lean body mass at those dosages.

Clinical Trials

In the 1970s, there was a flurry of interest in the United States for the weight loss effects of HCG, followed by a few German articles in the 1980s, and then very little since. After mostly equivocal results, most recommendations were that the HCG protocol was not effective for weight loss and should not be used.

There has been one meta-analysis that encapsulates some of this scientific work.12 The review examined 24 HCG weight loss studies published between 1966 and 1993, finding 14 randomized controlled trials, only one of which had conclusive data showing positive results (20-pound weight loss over 6 weeks for the HCG group, compared to 11 pounds for the placebo group). Subsequently, an effort to exactly duplicate the methodology of the reported positive study failed to find any difference between placebo and HCG injections.13 All remaining trials detailed in the meta-analysis failed to find any benefit in weight loss or other measured parameters for HCG injections over placebo. Some of these trials are discussed below.

An example of one of the early clinical trials randomized 40 obese women ages 20-40 years to receive intramuscular HCG (no dose listed) or placebo 6 days weekly for 6 weeks; weight, hunger, localized fat reduction, and mood were measured.4 Both groups followed a very low-calorie (approximately 500 calories) diet. Seven of the women were excluded from the final analysis, but intention-to-treat analysis was not done, compromising the final results. Both groups demonstrated the same loss of weight, and similarities were found in all other parameters measured.

Another study randomized 202 people to either HCG injections (125 mcg daily for 6 days of the week) or saline placebo injections for 6 weeks, while all were closely following the Simeons diet limited to 500 calories daily.8 After this initial 6-week period, there was a 6-week "weight maintenance" phase, and then a 6-week crossover treatment period. Measurements were made for body weight and percentage body fat, neither of which was different between the two groups. For example, over 6 weeks, the average body weight loss was 6.8 kg for the HCG group and 7.0 kg for the placebo group. The dropout rates for the HCG and placebo groups were similar between the two (57 and 49, respectively); this is not an easy protocol to follow, presumably accounting for the high dropout rate.

Another research group addressed the difficulties in following this diet by studying hospitalized (and therefore more closely watched and diet-controlled) obese women — six on the HCG injection protocol and five on a placebo injection — for six weeks in a double-blind fashion (randomization not mentioned).14 Both groups followed a 500 calorie per day diet. Numerous laboratory parameters, skinfold thickness, and circumference in several body areas were measured in the two groups. Results for the two groups for all of these categories were statistically similar; the weight loss was approximately 9 kg. Of note, urinary ketones and serum uric acid increased for both groups during the treatment periods, the latter possibly a concern for people with a history of, or at risk for, gout.

Sounding a bit like a broken record, a more recent study with a similar protocol except for a caloric intake just above 1000 calories daily (to address the blunted metabolic rate that can occur with severe calorie restriction) found no change in any of a myriad of laboratory and clinical measurements between placebo and HCG injections.15

The above-mentioned clinical trials all examined the original Simeons protocol using HCG injections for weight loss. More recently, the shift in the public's use of HCG has been to oral administration of HCG, primarily in a homeopathic form. Unfortunately, the medical literature is frustratingly mute on this version of the HCG protocol.

Dosing

There are numerous over-the-counter products with a variety of HCG dosages and forms. It is possible to purchase oral drops, pellets, and sprays, some with proprietary blends of other nutrients, such as amino acids. One product may dose the HCG at 10 drops three times daily, but its homeopathic strength of 6X would be difficult to compare to a 30X form mixed with several amino acids. Another propriety combination of HCG and amino acids (910 nanograms in 10 drops) is dosed 10 drops three times daily. The medical literature does not provide guidance about the most efficacious dosing for these over-the-counter formulations. The use of pharmaceutical-grade injectable HCG first proposed by Simeons and studied by the vast majority of clinical trials is 125 mcg intramuscularly or subcutaneously once daily 6 days per week. The use of recombinant alpha HCG for ovulation induction or assisted reproductive technology, as a comparison, is 250 mcg subcutaneously once daily for just one dose.

Adverse Effects

When adverse effects were followed and detailed, and this was not always the case, most of the clinical trials reviewed above found no significant adverse effect rate differences between the HCG treatment and placebo groups. Notable exceptions are the report of nipple tenderness11 and laboratory abnormalities (mentioned above), presumably due to the ketosis or rapid weight loss from severe calorie restriction. In addition, one review mentions adverse effects associated with HCG injections might include blood clots, headaches, restlessness, depression, and dizziness, although the source of this information is not listed; it is possible that these events were extrapolated from the use of HCG to treat infertility, given that the on-line drug reference Micromedex mentions thromboembolic disorders and ovarian hyperstimulation syndrome as possible adverse effects.6 Although not an adverse effect per se, the literature mentions one case of a women with infertility who, upon beginning injections of HCG for weight loss, became pregnant.15 There are, of course, dangers with rapid weight loss and severe calorie restriction, including the precipitation of gallstones and nutrient deficiencies.

Conclusion

Human chorionic gonadotrophin is a hormone most well-known for its supportive effect in pregnancy, with four different types of HCG having a wide range of effects on the fetus, placenta, and uterus. Less obvious is its relevance to overall adult physiology, in general, and weight loss, in specific, although one small clinical trial using HCG for men with testosterone deficiency did show an increase in lean body mass and body weight (so much for weight loss!) and a loss of body fat mass, supporting the claims of some of the HCG marketing machine. Most of the clinical trials were in the 1970s and 1980s, and followed the original Simeons method of 125 mcg intramuscular HCG administration combined with a 500-calorie diet. Minus one positive result that couldn't be corroborated, without exception, clinical trials failed to demonstrate a weight loss or physiological or psychological benefit to HCG over placebo. Adverse effects of HCG are rare, but may include the precipitation of gout, thromboemolobic events, and hyperstimulation of ovaries. A completely different set of adverse effects are possible when considering the totality of the HCG protocol, which involves a severely low calorie diet.

Recommendations

A risk-benefit approach to the analysis of the HCG diet protocol would dictate to not recommend this weight loss method. HCG injections have been examined and found to not be of use beyond the weight loss that would be expected with a 500-calorie a day diet. In addition, the use of HCG and such severe calorie restriction are not without risks. However, the homeopathic and liquid forms for sale and seemingly widely popular have not been subjected to any clinical trials, so it is difficult to say whether these forms would similarly be ineffective, even though the proposed HCG mechanism does not entirely make sense and would lead us to believe that even the oral HCG alternative to the Simeons protocol would also fail to lead to convincing weight loss. Obesity is on the rise, and many people are desperate for a kick start to lose weight and achieve health; this is the primary reason mentioned for the short-term use of the HCG protocol. Rather than involving HCG, perhaps the ideal approach for our patients does focus on a healthy diet, with calorie restriction in the short term and sustainable long-term changes in eating habits and lifestyle.

References

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5. U.S. Food and Drug Administration. Fraudulent HCG Products for Weight Loss. Available at: www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/MedicationHealthFraud/ucm282465.htm. Accessed December 10, 2011.

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10. Bowen T. HCG Effect on the Hypothalamus. eHow. Available at: www.ehow.com/facts_7358921_hcg-effect-hypothalamus.html. Accessed January 9, 2012.

11. Liu PY, et al. A double-blind, placebo-controlled, randomized clinical trial of recombinant human chorionic gonadotropin on muscle strength and physical function and activity in older men with partial age-related androgen deficiency. J Clin Endo Metab 2002;87:3125-3135.

12. Lijesen GK, et al. The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: A criteria-based meta-analysis. Br J Clin Pharmacol 1995;40:237-243.

13. Stein MR, et al. Ineffectiveness of human chorionic gonadotropin in weight reduction: A double-blind study. Am J Clin Nutr 1976;29:940-948.

14. Shetty KR, Kalkhoff RK. Human chorionic gonadotropin (HCG) treatment of obesity. Arch Intern Med 1977;137:151-155.

15. Bosch B, et al. Human chorionic gonadotrophin and weight loss. A double-blind, placebo-controlled trial. S Afr Med J 1990;77:185-159.