Complementary and Alternative Therapy for Weight Management

Anne E. Becker

Alexandra Perloe

Kate E. Nyquist

Lee M. Kaplan

Obesity is the worst epidemic of our time with more than 75 million adults and 15 million children and adolescents affected in the United States alone. There are an equal number of people in this country who are overweight without obesity; thus, more than two-thirds of adult Americans and a third of our youth have overweight or obesity. Moreover, the average weight of the population is rising, and the prevalence of obesity, particularly severe obesity, continues to increase. With its more than 60 related comorbidities, disorders of excess body weight have a powerful effect on the health, longevity, and quality of life of the overall population. Despite a strong expression of need from the general public, the public health sector, and the medical community, current treatments remain inadequate to the challenge. Lifestyle modification, including change in diet and physical activity, is the mainstay of treatment and prevention efforts. These changes can be promoted through a wide variety of approaches, including individual and group education and counseling, cognitive-behavioral therapies, structured diets and exercise programs, meal replacement therapy, and residential programs. Such interventions may be complemented by use of prescription or over-the-counter medications, or complementary approaches, which is the subject of this review. In patients with particularly severe or medically complicated obesity, bariatric surgery is often effective, but the significant risk associated with surgical interventions limits their use to less than 1 in 400 patients with obesity each year. Each of these therapies is associated with good short-term (e.g., 3 to 6 months) success, with at least 10% weight loss in more than 75% of treated individuals. The overriding challenge is maintenance of that success. With all except for surgical interventions, substantial weight regain is the rule, and much of our current efforts must be directed at developing strategies to limit this phenomenon. It is the common frustration with weight regain and the resulting “yo-yo” dieting that propels many people to seek a wide variety of standard and alternative therapies, some proven but many unstudied. Combined with the powerful cultural preference for thinness, these challenges frequently cause people with overweight and obesity to grasp for any program or product that promises success, no matter how improbable.

In evaluating patients with overweight or obesity, it is important to focus on both the causes of the excess weight and its medical and psychosocial consequences. Weight disorders, like most other diseases, arise from a combination of genetic predisposition and environmental influences. Unfortunately, more than 80% of people are genetically predisposed to overweight or obesity, and the changing environment over the past century has allowed this predisposition to be expressed. For different individuals, however, the specific causes of the excess weight vary, and it is important to distinguish metabolic, behavioral, and identifiable environmental (e.g., medications, brain injury, sleep deprivation) determinants. The relative contributions of these factors can be very helpful in determining the most appropriate treatment strategies. In addition, understanding the impact of the patient’s weight on his or her
health and physical, psychologic, and social functioning can be very helpful in directing the patient to appropriate intervention.

SOCIOCULTURAL CONSIDERATIONS

This review focuses on complementary and alternative medicine (CAM) treatment approaches used in U.S. populations for weight management, although we acknowledge use of folk and traditional strategies for weight management across diverse populations (1). In addition to health-related goals associated with weight loss, weight management is motivated by the social desirability of fitness in American society as well as the stigma associated with obesity. The strong cultural preference for slenderness is supported by mass media glamorization and routinization of thinness. Overweight and obesity also confer a social and economic disadvantage. For example, overweight during adolescence predicts lower educational attainment and lower chance of marriage among women when they reach adulthood (2). This phenomenon is far more prominent for disorders of excess body weight than for other chronic medical conditions. Similarly, there is an inverse relationship between socioeconomic status and central obesity (3). Moreover, the stigma of obesity is so pronounced that it is even associated to being in the presence of an individual with obesity (4).

POPULARITY OF CAM WEIGHT LOSS STRATEGIES

Given the high prevalence of overweight and obesity among Americans, the tangible health and social goals of weight management, and the high rate of weight regain even after successful weight loss, it is not difficult to understand the cultural appeal of weight loss. What is harder to fathom is how otherwise discerning and sophisticated consumers can so easily overlook the lack of empirical support for weight loss therapies pitched to them. Dieting—practiced at any given time by approximately 45% of American women and 30% of American men (5)—has become culturally normative in the United States. In 1958, obesity specialist Albert Stunkard made the observation that, “Most obese persons will not stay in treatment. Of those who stay in treatment, most will not lose weight, and of those who do lose weight, most will regain it” (6). Unfortunately, this statement is still true.

The high prevalence of overweight, the sustained interest in even normal weight individuals in staying fit, and the high recurrence of weight gain contribute to demand for complementary and alternative therapies for weight management. These therapies include natural supplements, acupuncture, and many popular diets, and are widespread in use. For example, an estimated 15% of adults (21% of women; 10% of men) have used a weight-loss supplement, including 8.7% within the past year. Women aged 18 to 34 years are the group most likely to take these supplements (7). Diet books are perennial best sellers, and they remain top-selling books for the Internet vending giant, amazon.com.

There is such a proliferation of products in the popular and CAM sectors for weight management that space does not permit an exhaustive review here. The authors have selectively reviewed available information from the scientific and medical literature relating to natural supplements, and nonpharmacologic, non-Western biomedical technologies, and present a brief discussion of popular commercial dieting approaches that draw upon biomedical principles, but have been more commonly accessed and promoted in the popular rather than the professional health literature. This chapter focuses on empirical evidence for the efficacy of these diverse therapies.

The adverse effects described in the randomized controlled trials (RCTs) on efficacy of natural supplements on weight management are also selectively reviewed. However, readers
should be cautioned that many serious adverse events that would have stopped a trial of a pharmaceutical agent would likely not have been identified by the authors’ search methods. Moreover, important safety issues, including significant adverse events, or supplement-drug interactions relevant to many clinical populations may not be fully addressed by the trials available for review.

NATURAL SUPPLEMENTS

Natural supplements in common use for weight loss were identified through selective systematic search of the scientific literature, perusal of popular Internet sites promoting or describing complementary and alternative natural therapies for weight loss, and anecdotal clinical experience. This included a search of Medline for scientific papers containing both terms (stem words and their derivatives) related to CAM and weight management in the title and/or abstract from 1950 through December 2007 to identify CAM weight-loss therapies that might have empirical support. The following CAM-related terms were searched: complementary, alternative, nutraceutical, herbal, natural, and supplement. The following weight management-related terms were searched: weight, satiety, appetite, diet, and full. A list of natural supplements was then generated from the content of the resulting articles. In addition, the Web sites www.chasefreedom.com, www.webmd.com, and www.drweil.com were checked to identify information about natural supplements in common clinical use. Finally, the retrieved reference list was reviewed for any omissions of nutritional supplements that had been encountered in clinical practice of eating and weight disorders management. A total of 56 agents (including some chemically related products) were identified (Table 14.1).

Using the 56 identified compounds and products as search terms, the scientific literature was searched to identify papers reporting RCTs evaluating these agents’ efficacy for weight loss and/or obesity therapy. The Medline database from 1950 to December 2007 was searched for papers that contained at least one of the 56 product terms and at least one of the following weight-related stem or derivative words in the title or abstract: weight, satiety, appetite, diet, full, overweight, obesity, and obese. The resulting search was then limited to papers that described RCTs. Only publications with available abstracts and full text in English were reviewed; those that reported on an RCT evaluating weight loss were retained for review. This search protocol resulted in approximately 60 original publications describing the results of RCTs with weight loss or maintenance as a key outcome.

LIMITATIONS

With few exceptions, only studies reporting on RCTs are reviewed. The authors recognize that this restriction imposes a Western biomedical efficacy standard on agents that may normally be used within popular traditions, based on alternative standards for efficacy. It also risks omitting agents for which RCTs may not be economically viable. Nonetheless, we believe that these limitations are compensated for by allowing allopathic practitioners a familiar and convincing standard for evaluation of each agent that allows comparison with studies of non-CAM strategies. Some of the described studies reported completer rather than intention-to-treat analyses. We urge caution in interpreting these results because of the bias that this approach is likely to introduce.

The nutritional supplements, nonpharmacologic approaches, and popular diets reviewed in this chapter do not represent an exhaustive list of putative therapies for weight management. Information that is not indexed in Medline may bias against healing traditions that do not disseminate information in English or in the Medline-indexed clinical literature. Moreover, indigenous use of compounds for weight management that have not been tapped by more mainstream traditions is likely to be significantly underrepresented in this approach. Finally, some of the agents investigated may have alternate names or spellings not included in our search.

TABLE 14.1 Complete List of Agents Included in Search for Randomized Controlled Trials (RCTs)

Agents for Which an RCT Measuring Weight Loss Was Identified	Agents for Which No RCT Measuring Weight Loss Was Identified
Bofu-tsusho-san	Alginate
Caffeine	Bisacodyl
Capsaicin/cayenne pepper	Cascara
Chitosan	Chaso
Chromium picolinate/chromium	Coleus
Conjugated linoleic acid	Cyperus root
Ephedrine (ephedra/ma huang)^a	Dandelion
Gallic acid	Germander
Glucommanan	Ginger root/Zingiber officinale
Goami no. 2	Ginkgo biloba
Green tea extracts/Camellia sinensis/epigallocatechin gallate	Ginseng
Guar gum	Globin digest
Guggul (Triphala Guggul, Gokshurado Guggul, Sinhanad Guggul)	Hoodia gordonii
5-Hydroxytryptophan	Inulin, Capsicum, L-phenylalanine
Hydroxycitric acid/Garcinia cambogia	7-KETO
L-carnitine	Kola nut
Magnolia officinalis and Phellodendron amurense	25-N-fen (nitrosofenfluramine)
Number Ten: rhubarb, ginger, astragulus, red sage, turmeric	Oligofructose
Pyruvate	Orshido
Synephrine/bitter orange/Citrus aurantium/phenylephrine	Pamabrom
Thiamin/arginine/caffeine/citric acid	Pausinystalia yohimbe
Tyrosine	Phytoestrogens
Yerba mate/Yerba maté, guarana, damiana	Plantago psyllium
	Potassium taurine bicarbonate/K-water
	Saw palmetto
	Senna, aloe, buckthorn, rhubarb root, cascara, castor oil (in tea)
	Spirulina
	St. John’s wort
	Theophylline, theobromine
	Usnic acid
	Wakame/fucoxanthin
	Willow bark/white willow
^aThese agents are omitted from this review because of the current FDA ban on supplements containing these products.

TABLE 14.2 Selected Summary of Findings of RCTs of CAM Treatments for Weight Loss

Compound (Other Names)	Reference	Study, Population, Composition, and Size	Study Design/Selected Outcomes	Duration	Key Findings on Weight (pos/neg/mixed)	Adverse Effects (Selected)
Ayurvedic (Triphala Guggul in combination with Gokshurado Guggul, or Sinhanad Guggul, or Chandraprabha Vati)	Paranjpe et al., 1990 (68)	77 adults (at least 20% above IBW) recruited; 48 completers	Double-blind RCT for weight loss	3 mo	Pos: treatment groups had significantly greater weight loss compared to placebo group (a range of 7.9-8.2 kg mean loss vs. 2.4 kg mean loss)	22 dropped out of study (10 from active treatment group for unspecified reasons; “minor side effects,” including nausea and mild diarrhea also reported in 8 on active treatment
Bofu-tsusho-san (BF): contains 18 “crude drugs,” including ephedrine and caffeine	Hioki et al., 2004 (65)	85 obese Japanese women (BMI 36.5±4.8 kg/m²) with impaired glucose tolerance and insulin resistance; 81 completers	Double-blind RCT body composition and weight loss	24-wk BF or placebo partially overlapping with 2 month diet and exercise	Unclear: significant reduction in weight (i.e., 10.8 kg in BF group and 9.4 kg in placebo group), and body fat at end of study compared with baseline in both groups; but no between-group differences evaluated	Cardiovascular or central nervous system effects not reported by subjects; loose bowel movements resulted in 3 withdrawals
Capsaicin/hot red pepper	Lejeune et al., 2003 (15)	91 overweight adults (BMI between 25 and 35 kg/m2)	Double-blind placebo-controlled trial for weight maintenance following a VLED; comparison groups stratified for characteristics but not randomized for this trial segment	3 mo weight maintenance following 4 wk VLED	Neg: weight regain during maintenance phase was not significantly different between groups	10 participants on active treatment complained about capsules on first or second day and had dosage reduced
Chitosan (Absorbitol)	Kaats et al., 2006 (59)	150 overweight adults; 134 completers	RCT for safety and efficacy on weight loss and body composition; supplement + behavior modification compared with placebo + behavior modification and compared with no treatment groups; weight loss + other outcomes	60 d	Pos: supplement group had significantly greater mean weight loss (−2.8 lbs) compared with placebo group (−.6 lbs) and compared with control group (+.8 lbs); supplement group also had significantly greater mean reduction in body fat mass lbs (−2.6) compared with placebo (+.6) and control (+.1)	None mentioned
Chitosan (Absorbitol)	Mhurchu et al., 2004 (60)	250 overweight/obese adults; 164 completers	Double-blind RCT for effect on body weight; intention to treat analysis	24 wk	Pos: the chitosan group lost significantly more weight than the placebo group (mean −0.4 kg vs. +0.2 kg)	10 SAEs (6 in placebo, 4 in chitosan group; SAEs in chitosan group included 3 hospitalizations and 1 cancer incidence); significantly more participants in chitosan group reported GI side effects (abdominal pain, bloating, constipation, indigestion, diarrhea) compared with placebo group
Chitosan (Absorbitol)	Ho et al., 2001 (62)	88 obese (body fat percentage >20% in males, >30% in females), hypercho-lesterolemic Asian subjects; 68 completers	Double-blind RCT for effect of Absorbitol (a salt of chitosan) on weight and body composition; intention to treat analyses	4-wk placebo run-in period followed by 12-wk treatment phase	Neg: no significant between-group differences in weight, BMI, lean mass or fat mass	No significant between-group differences in AEs; 7 active treatment vs. 5 placebo participants reported GI-related AEs, (i.e., epigastric discomfort, constipation, nausea, diarrhea, throat dryness)
Chromium (chromium picolinate [CrPic] and chromium polynicotinate)	Hockney et al., 2006 (33)	112 adults who met criteria for schizophrenia or schizoaffective disorder, all taking stable dose of antipsychotic medication	Double-blind RCT on efficacy for weight loss	3 mo	Neg: no significant between-group difference on weight change at 3 months	Authors report that the supplement was “well tolerated,” and that “no specific adverse effects were identified”; notably, midway through the study, new study participants were randomized to chromium polynicotinate vs. placebo because of a U.K. Foods Standards Agency recommendation that CrPic not be used as a nutritional supplement (due to genotoxicity in animals)
CrPic and Picolinic acid (PA)	Lukaski et al., 2007 (34)	83 premenopausal women (BMI: 18 to 30 kg/m²)	Double-blind RCT on weight, body composition, iron nutritional parameters (during a controlled diet)	14 days with all subjects on controlled basal chromium diet 12 wk treatment with CrPic vs. PA vs. placebo, with continuation of controlled diet	Neg: supplementation did not affect body weight or body composition; no between-group differences with respect to iron nutritional parameters	None mentioned. No adverse effects on iron nutritional factors found
CrPic-containing compound (also including, choline bitartrate, inulin, vanadium sulfate, manganese picolinate, capsicum, L-phenylalanine, peppermint oil, St. John’s wort extract 0.3% (compound is patented as Biotrol)	Hoeger et al., 1998 (30)	158 “moderately obese” adults; 123 completers	Double-blind RCT on weight loss and body composition	4-wk comparison of diet/exercise + supplement vs. diet/exercise + placebo	Mixed: Pos: diet/exercise/Biotrol (DXB) showed significant greater reduction in percent fat and fat mass and greater preservation of fat-free mass (all P<0.05) than the diet/exercise/placebo group Neg: no between-group difference in body weight or BMI	Reported as none
Conjugated linoleic acid (CLA)	Gaullier et al., 2004 (39)	180 healthy overweight adults (BMI 25 to 30) of which 157 completed study	Double-blind RCT on body composition and safety comparing CLA-free fatty acid (FFA), CLA-triacylglycerol, and olive oil placebo	1 yr	Pos: in those taking – CLA-triacylglycerol weight/BMI reduction minimal, yet significantly more than placebo at 1 yr Neg.: no difference in CLA-FFA vs. placebo in weight or BMI Pos: body fat mass (BFM) significantly lower in both CLA groups than in placebo (−1.7 kg in CLA-FFA and −2.4 kg in CLA-triacylglycerol)	At 1 yr, lipoprotein-a concentrations were higher in both CLA groups than in placebo, and thrombocyte levels were higher in CLA-FFA than placebo; AEs were “evenly distributed” among groups; GI symptoms most frequently reported
CLA	Gaullier et al., 2007 (40)	118 healthy overweight adults randomized (18 to 65 yr, BMI 28 to 32) 105 who completed at least one post-baseline visit included in analyses presented here; 93 completers	Double-blind RCT comparing CLA to olive oil placebo on BFM and BMI	6 mo	Pos: significant difference between groups in BFM decrease; percent BFM with CLA showing greater decrease than placebo Neg: no significant difference between groups in weight or BMI, except in subjects with BMI ≥30, who showed significant weight loss (1.9 kg) and BMI reduction in CLA group compared to placebo	AEs reported by 37% of subjects, with similar frequency in CLA and placebo groups; most AEs in GI and musculoskeletal systems; one male subject on CLA suffered a moderate acute myocardial infarction, which was deemed “possibly” linked to treatment; significant between-group differences reported for insulin c-peptide and for CRP (both significantly higher in CLA group at 6 mo)
CLA	Malpuech-Brugère et al., 2004 (44)	90 healthy “moderately overweight” adults, BMI 25 to 30); 84 randomized; 82 completed study	Double-blind RCT on body composition, weight, and BMI comparing 2 different CLA isomers (at 2 dosages) with placebo	6 wk run-in period with all on placebo, then 18-wk intervention	Neg: no significant differences in weight, BMI, waist-to-hip ratio, percent body fat, BFM, or lean body mass between baseline and end of study in any of the study groups	Elevated liver function marker in 1 participant and menstrual complaints in 1 participant (both participants in a CLA group)
CLA triglyceride (CLA-TG)	Gaullier et al., 2005 (48)	134 healthy overweight adults [from previous Gaullier study (40)]; 125 completers	Open extension study of previous double-blind RCT [Gaullier et al. (40)] for effect of CLA-TG on body composition and safety	1 yr	Body weight, BMI, and BFM were reduced in CLA treatment groups at 24 months (compared to baseline) and at 24 months (compared to 12-month start time for CLA) in group that had started on placebo	7 AEs felt to be CLA related; these were rated as mild and mostly GI complaints; lipoprotein-a levels and leukocyte and thrombocyte counts increased with CLA
CLA	Larsen et al., 2006 (49)	122 healthy Caucasian adults with BMI 28 to 35; 101 randomized, 83 completed at least 26 weeks of treatment and included in “modified” intention to treat analysis	Double-blind RCT with two treatment arms for weight regain after 8-wk dietary run-in with energy restriction	1 yr after 8-wk dietary run-in	Neg: no significant between-group difference in change in body weight or fat mass	A statistically significant increase in leukocyte concentration was observed in CLA-treated group; AEs were common but did not differ between groups
Glucomannan (purified fiber)	Walsh et al., 1984 (8)	20 obese women	RCT for weight loss and cholesterol	8 wk	Pos: weight loss: mean 5.5 lbs (±1.5) at 8 wk; significantly more than placebo (P<0.005); serum cholesterol decrease significantly more than placebo	No AEs reported by study participants
Glucomannan	Vido et al., 1993 (9)	60 overweight children under 15 yr (mean 11.2 yr)	Double-blind RCT on weight and satiety	2 mo	Neg: no significant between-group difference in weight loss	No between-group differences except in lipid profile (including significantly higher triglycerides in supplement group)
Goami no. 2 (fiber-rich rice)	Lee et al., 2006 (14)	11 healthy nonobese adults and 10 healthy obese adults (BMI >25)	RCT crossover design for weight, BMI, body fat content, biochemical parameters	4-wk diet + supplement, 6-wk washout, 4-wk diet with alternate supplement	Pos: obese and healthy control subjects each had a significantly greater change in BMI after supplement diet phase than control phase	Most subjects noted digestive difficulty; one subject excluded due to poor compliance
Green tea	Kovacs et al., 2004 (54)	104 overweight or moderately obese adults (BMI 25 to 35)	Double-blind comparison on weight maintenance after a period of weight loss from VLED; group assignment stratified by selected traits	13-wk weight maintenance period (with green tea or placebo) following weight loss with VLED	Neg: during maintenance period, weight regain was not significantly different between treatment groups	None mentioned
Green tea in participants with habitual high vs. low caffeine intake	Westerterp-Plantenga et al., 2005 (53) [a follow-up to Kovacs et al. (54)]	76 overweight and moderately obese subjects; including 38 habitual low-caffeine consumers (<300 mg/d caffeine) and 38 habitual highcaffeine consumers (>300 mg/d caffeine)	Double-blind RCT on weight maintenance after weight loss during VLED with green tea vs. placebo in high vs. low habitual caffeine consumption groups	3-mo weight maintenance trial following 4-week VLED	Pos: during weight maintenance: in the low-caffeine intake group, green tea recipients regained less weight compared with placebo subgroup Neg: no between-group differences in high caffeine intake group	Reported as none
Green tea (extract; in a compound also containing L-tyrosine, caffeine, cayenne, and calcium carbonate)	Belza et al., 2007 (56)	80 overweight to obese adults 75 completers	Double-blind RCT on thermogenesis, body fat loss; intention to treat analysis	8 wk hypocaloric diet + simple release supplement vs. enteric coated supplement vs. placebo following 4-week low cal diet	Neg: no significant between-group differences in weight loss	Self-reported AEs were frequent (with a majority relating to headache and GI complaints) but not different between groups.
Green tea (including epigallocatechin gallate)	Chan et al., 2006 (58)	34 Chinese adult women with polycystic ovary syndrome and BMI ≥28; 29 completers	Double-blind RCT on weight and body fat; intention to treat analysis	3 mo	Neg: no significant between-group differences in weight, body fat, or BMI	No “significant side effects” recorded; green tea group had statistically significant increase in fasting triglyceride after treatment
Guar gum (water-soluble fiber)	Pasman et al., 1997 (10)	31 obese women	RCT on weight maintenance after weight reduction	14 mo guar gum vs. no supplement after a 2-mo very lowcalorie diet	Neg: no effect on long-term weight maintenance	None mentioned
Guar gum (water-soluble fiber)	Kovacs et al., 2001 (13)	28 mainly overweight adult men	RCT crossover on energy intake, body weight, appetite, and satiety; 3 comparison treatments: semi-solid meal + supplement vs. semi-solid meal vs. solid meal	Baseline 1 wk with selfselected diet; then 2-wk intervention, 4-wk washout, repeated twice for two alternates	Neg: no significant difference in weight loss among treatments	Diets were “well tolerated,” supplement resulted in higher level of nausea and flatulence
(−)-Hydroxycitric acid (HCA) (in Garcinia atroviridis)	Roongpisuthipong et al., 2007 (24)	50 obese Thai adult women; 42 completers	Double-blind RCT comparing supplement vs. placebo during a 1,000 kcal/day diet	8 wk	Pos: HCA group lost significantly more weight at 8 wk than did placebo group (mean loss of 2.8 kg vs. 1.4 kg) and had greater reduction of BMI	None mentioned
Calcium-potassium salt of (−)-hydroxycitric acid (HCA-SX), and HCA-SX plus niacin-bound chromium (NBC) and Gymnema sylvestre extract (GSE) (“HCA-SX formula”)	Preuss et al., 2005 (23)	90 adult obese subjects; 82 completers	Combination of data from two double-blind RCTs assessing efficacy of HCA-SX and “HCA-SX formula” vs. placebo on weight, BMI, lipid profiles	8 wk	Pos: HCA-SX + NBC + GSE group had significantly greater weight loss (mean loss of 6.1 kg) and BMI reduction than -HCA-SX and placebo groups; HCA-SX also had significantly greater weight loss (mean of 4.9 kg) and BMI reduction than placebo group	AEs were mild and transient; no between-group differences in the number of participants reporting AEs
HCA (as Garcinia cambogia)	Mattes and Bormann, 2000 (22)	89 mildly overweight adult females; analysis was subgroup of study of “compliant” females	Subgroup analysis of “compliant” participants from an RCT on weight, body composition, appetitive variables comparing 1,200 kcal/day diet + HCA vs. diet + placebo	12 wk	Mixed: Pos: significantly greater, though modest, weight loss in HCA group: (3.7 kg compared with placebo (2.4 kg) Neg: no significant difference in fat mass reduction between groups	None mentioned
HCA (as Garcinia cambogia)	Heymsfield et al., 1998 (27)	135 overweight adults; 84 completers	Double-blind RCT on body weight, BFM; intention to treat analysis	12 wk (high-fiber/low-energy diet)+ HCA vs. diet + placebo	Neg: no significant between-group difference in weight loss	Some headache, upper respiratory symptoms, GI symptoms reported, but no significant difference between reports in HCA and placebo groups
HCA (in a supplement also containing kidney bean pod extract and chromium yeast) with supplement containing asparagus, green tea, black tea, guarana, mate, and kidney beans	Opala et al., 2006 (25)	105 overweight adults; 98 completers	Double-blind RCT on weight, body composition	84±2 d (12 wk) diet (1,500 kcal/day) + “increased exercise” by walking + supplements vs. diet/exercise + placebo	Mixed: Neg: no significant between-group difference in weight or BMI reduction Pos: statistically significant decrease in body fat measured by skinfold in supplement group	No changes in lab safety parameters; significantly greater GI symptoms in supplement group
5-Hydroxytryptophan (5-HTP)	Cangiano et al., 1992 (18)	28 obese adults; 20 completers	Double-blind RCT 5-HTP vs. placebo	12-wk study (divided into two 6-wk periods; no diet prescribed in first period, 5,040 kJ/d diet prescribed in second period)	Unclear: subjects receiving 5-HTP showed significant weight loss compared to baseline; placebo groups did not show significant weight loss from baseline; no between-group comparisons presented	“Episodic” nausea reported by 80% of subjects given 5-HTP during first 6 wk, and 20% during ensuing 6 wk
L-Carnitine	Villani et al., 2000 (37)	36 adult Australian women (mean BMI 24.7±0.66, mean percent body fat 35.2%); 28 completers	Double-blind RCT on body composition, resting energy expenditure (weight included); random assignment of pairs after BMI matching	8 wk with concurrent walking 4 days/week	Neg: no significant between-group differences in weight, fat mass, or fat-free mass after intervention period	Half (9 of 18) the L-C group reported nausea and diarrhea; 5 of the L-C group withdrew due to side effects, including 4 with persistent diarrhea
L-Carnitine	Elmslie et al., 2006 (38)	60 bipolar patients taking sodium valproate and with clinically significant weight gain (BMI>25); 44 completers	Double-blind RCT on weight change; intention to treat analysis	26-wk trial with energy-restricted low-fat diet, encouragement to exercise ≥30 min 5 times per week, and lifestyle advice	Neg: no significant between-group difference in weight, BMI, or waist circumference reduction	None mentioned
Magnolia officinalis and Phellodendron amurense extract (supplement called NP 33-39)	Garrison and Chambliss, 2006 (66)	42 healthy, overweight premenopausal women who typically eat more in stressful situations; 28 completers	Double-blind RCT on weight change and other measures	6 wk	Neg: no significant weight change between baseline and end of treatment for treatment group; no between-group differences in weight loss amount reported	Two participants on supplement withdrew due to side effects (heartburn, shaking hands, perilabial numbness, sexual dysfunction, and thyroid dysfunction) deemed by study physician “possibly related” to treatment; fatigue and headaches deemed “probably not related”
Number Ten (NT) (an herbal supplement of rhubarb, ginger, astragulus, red sage, turmeric) supplement with gallic acid (GA)	Roberts et al., 2007 (28)	105 healthy overweight adults randomized	RCT comparing two doses of NT+GA to placebo	24 wk, with interim analysis at 8 wk showing negative results; study discontinued at that time	Neg: at 8 wk, low-dose group lost 1.2% of body weight, which was statistically greater that weight loss in placebo; high dose group was not different from placebo; study discontinued due to negative results Neg: at 24 wk, analysis of completers showed no difference between NT-GA supplement group and placebo on weight loss	No significant between-group difference in effects on blood pressure or pulse rate of laboratory value changes, but there was a statistically significant drop in Hgb and Hct in high-dose NT-GA group compared with placebo and a drop in uric acid in NT-GA groups compared with placebo
Pyruvate	Kalman et al., 1999 (20)	26 healthy overweight adults	Double-blind RCT on weight and body composition	6-wk trial with placebo control concurrent with 3 d per wk exercise routine	Unclear: statistically significant but modest reduction from baseline in weight (-1.6%), in BF (−14.0%) at 6 wk compared to no change in placebo group; between-group differences not calculated	None mentioned
Pyruvate	Stanko et al., 1994 (19)	34 adults with hyperlipidemia (cholesterol ≥5.70 mmol/L), of whom 16 were ≥20% above “ideal body weight”	RCT on weight and fat loss and concentrations of cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride	4 wk on lowcholesterol/low-fat diet; followed by random assignment to pyruvate or placebo for 6 wk	Pos: body weight and fat decreased to a greater extent in the pyruvate group than in the placebo group, though losses were small in both groups (weight loss of −0.7±0.2 kg with pyruvate vs. −0.1±0.2 kg with placebo; body fat loss of −0.5±0.2 kg vs. −0.1±0.1 kg)	Side effects were more frequent in pyruvate supplement group participants: gas and bloating (65%) loose stool (24%) and diarrhea (35%)
Thiamin, arginine, caffeine, citric acid (TACC)	Muroyama et al., 2003 (21)	31 subjects with high percent body fat (≥25%); 29 completers	RCT on body composition	16-wk trial concurrent for 12 wk with dietary intervention	Mixed: only triceps skinfold thickness was significantly reduced in TACC group compared with the control group at 16 weeks	None mentioned
White bean extract (Phaseolus vulgaris)	Udani and Singh, 2007 (63)	27 healthy adults (BMI 23 to 31); 25 completers	Double-blind RCT for effect of white bean extract on weight loss	4-wk supplement vs. placebo concurrent with diet, exercise, and behavioral intervention	Neg: there was no significant between-group difference in reduction of weight or waist size	There were no side effects or adverse events during the trial; there were no significant between-group differences or differences between baseline and the close of the study on safety parameters (lab studies)
YGD capsules (an herbal preparation containing yerba mate from leaves of Ilex paraguayensis), guarana (seeds of Paullinia cupana) and Damiana (leaves of Turnera diffusa var. aphrodisiaca)	Andersen and Fogh, 2001 (64)	47 overweight adults (BMI 25.8-30.4)	Double-blind RCT on weight loss	YGD vs. placebo supplementation for 45 days while maintaining current normal diet	Unclear: no tests of statistical significance were presented but mean weight loss after 45 d of 5.1±0.5 kg in YGD group vs. only 0.3±0.08 kg in placebo group	None mentioned
Nonpharmacologic Therapies to Promote Weight Loss
Acupuncture	Wang, 2002 (74)	120 adolescents and adults with “simple obesity”	RCT (control group intervention included a diet tea and dietary instruction rather than placebo)	30 d (30 min, once every other day, for 15 sessions Control group: 1 mo diet tea + dietary instructions “forbidding” carbohydrates	Pos: BMI reduction significantly greater in acupuncture group: loss of 2.45±0.53 vs. 1.04±0.47	Not mentioned
Electroacupuncture	Hsu et al., 2005 (72)	72 obese women in Taipei (BMI >30); 63 completers	RCT comparing 3 groups: (1) electroacupuncture, (2) sit-up exercises, and (3) no treatment (no placebo) on weight, BMI, and waist circumference (WC)	6 wk acupuncture treatment, 40 min twice a week; sit-ups 10 times/d	Pos: percent reduction in BW, BMI, and WC significantly greater for electroacupuncture group than no-treatment group and sit-up group	No subjects withdrew due to adverse effects; 3 subjects developed “mild” ecchymosis, one patient noted abdominal discomfort after electroacupuncture
Hypnotherapy	Stradling et al., 1998 (77)	60 obese adults (BMI >30) with obstructive sleep apnea; 46 completers	RCT on weight loss, with three arms: (1) hypnotherapy with suggestions about food intake (active treatment); (2) dietary advice alone; (3) dietary advice with hypnotherapy with stress reduction	18 months: 2 sessions of hypnotherapy a month apart with instructions to use it daily	Neg: no significant between-group differences in weight loss; at 18 mo, only the hypnotherapy with stress reduction group showed significant, but small, weight loss: 3.8 kg (±5.8) from baseline	None mentioned
Abbreviations: RCT, randomized controlled trial; CAM, complementary and alternative medicine; Pos, positive; Neg, negative; IBW, ideal body weight; BMI, body mass index; RMR, resting metabolic rate; BP, blood pressure; SAE, serious adverse event; GI, gastrointestinal; AE, adverse event; VLED, very low energy diet; BFM, body fat mass; NCA, hydroxycitric acid.