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W E I G H T- L O S S S U P P L E M E N T S A N D A LT E R N AT I V E T R E AT M E N T S

Because of the difficulty of maintaining long-term weight loss, the field of weight control is open to much misinformation and commercial abuse. This extends to weight-loss products and services. These are constantly changing, and new products and programs are being added constantly, so it is not possible to provide an exhaustive review of all alternative treatments available. In addition, for many weight-loss products and services there is little published information and there have been no trials at the level of evidence required for these guidelines. Recent surveys have nevertheless shown that over 7 per cent of the population in the US regularly use non-prescription weight-loss products; the figure increases to almost 30 per cent for obese young women. Among users of prescription weight-loss products over one-third also use non-prescription products.1

10.1

W E I G H T- L O S S S U P P L E M E N T S

Popular non-prescription weight-loss treatments have been reviewed in detail by Egger et al.2 There have also been more general reviews of nutritional food supplements3 and a wide range of alternatives for weight loss.4 Table 10.1 shows the most commonly available non-prescription supplements and summarises the evidence and risks associated with each of them. The products are discussed here in three categories: those with a scientific rationale and an acceptable level of (positive or negative) evidence; those with a scientific rationale but no acceptable level of (positive or negative) evidence; and those with no scientific rationale and/or no acceptable level of (positive or negative) evidence.

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Source Rind of a type of citrus fruit Inhibits lipogenesis from CHO; reduces appetite through gluconeogenesis Spicy foods; chilli Seeds of a climbing shrub from Brazil and Uruguay Synthesised from lysine Fruit/jams Increases satiety ** * (in food) Fat metaboliser ** Increases metabolic rate ** * (caffeine) Yes No No Increases energy expenditure ** * (in food) Yes x -tive No Proposed action Theoretical rationalea Supporting evidenceb Potential risk Seawrack or bladderwrack (types of seaweed) Marine crustacean shells Inhibits fat absorption * (with low energy diet) Supplement Extract from maidenhair Stress reduction, prevents oedema Improves insulin sensitivity * -tive Yes Yes Increases metabolic rate through increased activity of thyroid gland * No * Yes

Table 10.1

Constituent

Active ingredient

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Brindleberry

Hydroxycitric acid (HCA)

Peppers

Capsaicin

Caffeine/ guarana

Caffeine

L-carnitine

L-carnitine

Fibre/pectin

Water-soluble dietary fibre-polymer of galacturonic acid

Fucus vesiculosus kelp

Iodine

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Chitosan

Deacetylated chitin (amino polysaccharide)

Chromium picolinate

Soluble chromium

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Identification and assessment of common ingredients in popular weight-loss supplements

Gingko biloba EGb761

Flavonoid, terpenes

Table 10.1

Constituent Extract from seeds Soy beans Seeds, flowers and bark of tree Extract from plant Component of liver/muscle Prevents fat accumulation in liver Perennial herb Antidepressant * Oestrogenic properties; increases circulation Antioxidant. Benefits circulation by decreasing oedema; increased flushing No Increases fat transport * No Antioxidant; benefits circulation No

Active ingredient

Source

Proposed action

Theoretical rationalea

Supporting evidenceb

Potential risk

Grapeseed extract

Bioflavonoids

Soy lecithin

Phosphoplipid

Horse chestnut

Saponins

Dried sweet clover

Isoflavine

No No Yes

Inositol

Vitamin-like compound

St Johns wort

Not clear

a. x = theory is inaccurate/disproved; - = no evidence supporting theoretical rationale in weight loss; * or ** = level of evidence supporting rationale in weight loss

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10.1.1

Supplements with a scientific rationale and some supporting evidence

Brindleberry
Brindleberry (Garcinia camboia or G. indica) comes from the rind of an exotic citrus fruit, the Malabar tamarind; the active ingredient in the rind is hydroxycitric acid (HCA), which inhibits the extra-mitochondrial enzyme adenosine triphosphate-citrate (pro-3S)-lyase. It is marketed as an appetite suppressant and fat store inhibitor. Of a number of studies published to date examining the effects of HCA on weight loss in humans, only two have been controlled and randomised,5,6 although both were short term. Neither study found any difference between obese individuals given HCA and those given a placebo over 12 weeks. The study by Heymsfield,6 however, has been criticised for not measuring the appetite-suppressant effect or the bioavailability of HCA.7,8 It has also been suggested that the high-fibre diet used in the study may have limited bioavailability, leading to a lack of effect.8 In another 12-week RCT study subjects receiving HCA showed a significantly greater reduction in body weight compared with those receiving a placebo (3.73.1kg as opposed to 2.42.9kg), but no effects on appetitive variables were observed.9 The suggestion that HCA can increase fat oxidation has also not been supported in a three-day study of supplementation.10 Furthermore, acute doses of HCA, even when provided in large quantities, do not increase total fat oxidation in vivo in endurance-trained humans.11 There is thus no convincing evidence supporting the use of brindleberry for weight loss.

Caffeine
Caffeine is one of the most widely consumed drugs in the world. It is also the main constituent of natural products such as guarana (Paullinia cupana), which is derived from a South American vine leaf, is promoted for its stimulant effects and weight loss, and is found in several non-prescription weight-loss products. Caffeine is a central nervous system stimulant that increases circulating epinephrine through a de-inhibitory effect on adenosine receptors and suppresses lipolysis by inhibiting adenylate cyclase activity.12 This results in a greater availability of free fatty acids in the bloodstream for oxidation and, hence, greater potential use of fats in the energy cycle. The role of caffeine in increasing free fatty acids in the circulationwhether mediated through norepinephrine or notis now well accepted,12-14 although it has not always been demonstrated.15 The release of free fatty acids helps spare glycogen in endurance events.16 Caffeine has been shown to stimulate the metabolic rate in young, elderly and obese individuals by 7 to 22 per cent for three to 24 hours after ingestion.17,18 A number of short-term controlled studies have shown some effects on thermogenesis and weight loss,19,20 although possibly less so in the obese19 and the elderly.21 Caffeine has also been shown to decrease the perception of work effort.16,22 Nine studies examining the effects of caffeine and weight loss in humans have been reported to date.2 Only one separated the effect of caffeine (200 milligrams daily) added to an energy-restricted diet in a placebo-controlled double-blind trial,20 it was reported that caffeine did not result in greater weight loss than diet alone. The
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remaining studies examined the effectiveness of caffeine in combination with soluble dietary fibre and chromium or the sympathomimetic agent ephedrine. Caffeinechromium-dietary fibre combinations have not been found to cause greater weight loss, but the caffeine-ephedrine combination has.23,19 Molnar et al. for example,24 showed a greater decrease in body weight (14.4 versus 2.2 per cent) and body fat (6.6 versus 0.5 kilograms) in adolescents after 20 weeks of treatment with a caffeineephedrine mix than with a placebo, with 81 per cent of subjects in the treatment group decreasing their body weight by at least 5 per cent compared with only 31 per cent in the control group. The combination of guarana (which is exceptionally high in caffeine) and ma huang (which contains ephedra, a source of ephedrine-type alkaloids) has recently been examined in an eight-week randomised double-blind placebo-controlled study of overweight men and women.25 Active treatment produced more weight loss (4.0 versus 0.8 kilograms) and fat loss (2.1 versus +0.2 per cent) than the placebo, but only 36 per cent of subjects completed the study. Many subjects withdrew because of side effects such as a dry mouth, insomnia and headache. Nutritional supplements containing ephedra have been linked to numerous episodes of ephedrine toxicity,26,27 and large doses of caffeine can induce cardiac arrhythmia.28 It is important to be aware of the potential adverse effects of these drug combinations.3 In a sophisticated analysis of the mechanisms involved in the anti-obesity effect of oolong tea, Japanese researchers showed a lipolytic effect of caffeine as well as suppression of pancreatic lipase activity.29 Relative to placebo, green tea extract (containing caffeine and catechin polyphenols) produces a greater increase in 24-hour energy expenditure and an increase in fat oxidation. In contrast, equivalent amounts of caffeine have no effect.30 Dulloo et al. have proposed that the thermogenic properties of green tea may reside primarily in an interaction between the high content of catechin polyphenols and caffeine and sympathetically released noradrenaline.31 Since caffeine consumption is part of many peoples lifestyles and since current data suggest no adverse effects of its use in moderation, continued moderate use can widen the scope of weight-loss eating plans. At best, it may offer some mild weightloss benefit. Although caffeine and ephedrine do appear to have a weight loss effect, the side effects of this combination appear to make it unsuitable for general use. There is at present no evidence for the use of guarana as a weight-loss supplement alone, although it is known to have stimulatory effects.

Chitosan
Chitosan is an amino polysaccharide derived from the powdered shells of marine crustaceans such as prawns and crabs. It forms the basis of a range of nonprescription products. As a food supplement, its positive anions are supposed to bind to negatively charged lipids from dietary fats through intestinal viscosity,32,33 preventing fat digestion and reducing fat storage. A further proposed mechanism is through inhibition of pancreatic lipase, which is necessary for fat absorption.

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A number of trials have shown a weight-loss effect in humans when chitosan is given with a low-energy diet for up to four weeks. However, a meta-analysis that pooled the studies results34 showed that the average amount of weight lost (3.3 kilograms) in the chitosan group compared with the controls would require a faecal fat loss of 100 grams a day. This would not seem possible given a low energy intake of 4 to 5 megajoules. It seems, therefore, that other mechanisms are at play or that there are flaws in the studies. In a recent randomised double-blind placebo-controlled trial, no effect of chitosan was found when there was no planned reduction in food intake.35 The authors admit that higher dosages still need to be tested, but it appears that, at least in the absence of a low-energy diet, chitosan has no effect on weight loss. A further randomised controlled trial showed that chitosan did not reduce body weight in overweight subjects over a four-week period,35 nor did it reduce plasma lipids or obesity in hypercholesterolaemic obese Asian subjects over a 16-week period.36 A positive effect of the substance with a low-energy diet may be plausible given that, as a malabsorptive agent, it may reduce future fat intake, but it would not decrease existing body fat in the absence of a negative energy balance. This was demonstrated in one of the few well-structured studies on chitosan published to date.35 Appropriate dosage levels of chitosan are untested, and loss of nutrients could be a problem. More studies are necessary to provide proof of its effectif there is oneand under what circumstances.

Chromium
The trace element chromium is involved in the control of blood sugars. Its exact biological role in humans is uncertain, although it is thought to function in insulinsignalling pathways as a component of the glucose tolerance factor.37 Chromium picolinate, an organic derivative of chromium, is used in many weight-loss formulas to increase chromium absorption. Chromium could theoretically help weight loss by enhancing the insulin-stimulated synthesis of the appetite-suppressing neuropeptide serotonin or by stimulating protein synthesis and thus energy use. A number of double-blind placebo-controlled studies have reported on the effects of chromium supplementation and exercise on body composition in non-obese individuals. Two have shown a greater effect on fat loss with supplementation38,39 but have been criticised on methodological grounds.40 A number of other studies have shown no effect.41-47 However, niacin-bound chromium given to modestly dieting and exercising African-American women has been shown to be associated with a significant loss of fat and sparing of muscle compared with a placebo over a twomonth treatment period.48 Two further studies of obese individuals randomised to either diet or diet-plus-exercise programs have failed to show greater weight and fat loss with chromium supplementation.49,50 On the basis of current evidence, therefore, there is little theoretical or practical support for using chromium supplements to assist with weight loss. Excess ingestion of chromium supplements may also cause serious renal impairment51 and there has recently been a suggested cancer link with use of the substances, prompting the UK Foods Standards Agency Expert Group on Vitamins and Minerals to advise people not to take chromium picolinate.104

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10.1.2

Supplements with a scientific rationale but no acceptable evidence

Capsaicin
Capsaicin is the major pungent ingredient of hot chillies and peppers. Generally, it is available in foods, but recently it has been marketed through supplements in the form of pepper, cayenne and capsaicin capsules. Capsaicin selectively activates afferent neurones, primarily those associated with pain perception, in the mouth.52 The neurones release a complex array of neuropeptides, including cholecystokinin, which is thought to suppress food intake.53 Capsaicin may also increase the secretion of epinephrine, which stimulates gluconeogenesis and lipolysis, and increases oxygen consumption,54 thermogenesis55 and gastric emptying rate.56 Thus, the proposed effects of capsaicin in weight loss are through reduced energy intake and increased energy expenditure. Little work on the appetite-suppressant effects of capsaicin has been done in humans. One study has shown, however, that an entree of spicy food may reduce the intake of food in a main meal by approximately 840 kilojoules;57 this effect may be increased when caffeine is also consumed.58 Other studies by the same group have shown that ingestion of red pepper increases diet-induced thermogenesis and lipid oxidation in Japanese females.59 Although capsaicin can increase energy expenditure in lean young women, there is evidence it does not do this in obese young women.60 There is also some evidence of a sustained increase in oxygen consumption following a meal containing a chilli extract.61 However, some studies showed no changes in oxygen consumption, fat utilisation or body temperature.62,63 Thus, while spicy foods containing capsaicin may be enjoyed by those in a weightcontrol program, there is no evidence that capsaicin exerts a thermogenic effect if ingested as a supplement rather than as a whole food, and there are no long-term controlled studies demonstrating the effects of capsaicin on weight loss.

L-carnitine
L-carnitine is a non-essential amino acid supplied by a normal diet, particularly meat, but also synthesised by the liver, kidneys and brain from methionine and lysine. Carnitine plays an important role in fat metabolism, transporting fats into the mitochondria for energy production. It has therefore been hypothesised that increasing the availability of carnitine will increase the transport of fat into the mitochondria and the rate of fat oxidation. On this basis, carnitine has been widely marketed as a fat burner or fat-loss agent.64 Two studies have shown no changes in the rate of fat oxidation following L-carnitine supplementation in humans.65,66 In addition, eight weeks of L-carnitine ingestion combined with walking did not significantly alter the total body mass or the fat mass of overweight women compared with a placebo combined with walking.67 There are thus no studies that support the use of L-carnitine for long-term weight loss.

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Dietary fibre
Pectin is a form of soluble dietary fibre. Foods high in fibre are filling and can lead to early satiation during meals and snacks. This should have a beneficial effect in treating obesity by decreasing total energy intake. Foods high in dietary fibre also have a lower energy density since dietary fibre contributes fewer kilojoules than other carbohydrates.68 Whether particular types of fibre added to dietary supplements in small amounts have any direct effect on weight loss, however, is unproven. One study claimed that as little as 5 grams of pectin could delay gastric emptying and increase satiety,69 but the subjects were not overweight and no weight-loss effect was shown. Another small study, of eight overweight people in Germany, claimed success for a formula diet containing 3 grams of apple pectin and 14.3 grams of wheat bran;70 however, there was no control group, the formula diet was 2800 kilojoules, and the study lasted only two weeks. Longer term studies have shown no effects on weight loss from fibre supplements.50,71 A diet high in fibre-rich foods, on the other hand, has been shown to have a positive effect for weight loss.72 Thus, although dietary fibre may have an important role to play in weight management, there is no evidence that supplements containing small amounts of fibre such as pectin have any influence on weight loss. A recent meta-analysis suggests that another viscous fibre, guar gum, is also not efficacious for reducing body weight.73

Iodine
Fucus vesiculus is a form of seaweed, or kelp. Seaweeds are rich in iodine, a mineral that plays a role in the normal action of the thyroid gland. Since the thyroid gland controls metabolic rate, products high in iodine are promoted as a way of speeding up the bodys metabolism, thereby burning more energy, which is supposed to translate into weight loss. It is well documented that excess iodine can lead to hyperthyroidism and in some cases, especially in the elderly, can result in weight loss. Hyperthyroidism and hypothyroidism have also been shown to be stimulated by an excessive intake of iodine through kelp tablets or eating iodine-rich seaweed.74,75 The human thyroid gland can, however, tolerate wide fluctuations in iodine supply because feedback mechanisms operate between the thyroid and the pituitary. Although obesity can result from hypothyroidism, very few cases of obesity are caused by the condition. There is no evidence that taking extra iodine in the form of kelp can lead to weight loss in non-thyroid deficient individualsexcept in a few rare cases in which excessive intake may cause hyperthyroidism, with its accompanying problems, including weight loss. There are also potential risks of a very high iodine, or kelp, intake,74,75 especially in older adults, although the quantities of iodine in most weightloss supplements are unlikely to pose a significant health risk, unless products are taken in excess.

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Ginko
Ginkgo biloba (EGb 761) is the ancient maidenhair tree and its leaves contain flavonoids. Gingko is sometimes promoted for stress reduction or for cerebral insufficiency in older people, but it is also present in some weight-loss products. Its proposed association with weight loss comes through inhibiting stress-induced corticosteroid hypersecretion. Ginkgo supplements have been associated with a reduction in adrenal peripheral benzodiazepine receptors76 and hence may reduce stress. Other proposed attributes of ginkgo are as an antioxidant and its action in improving circulation. Management of stress has been suggested as one of the cornerstones of long-term weight loss.77 There is a close relationship between the serotonin-influencing drugs used in depression and the treatment of stress and the drugs currently or previously prescribed for weight control. There may therefore be benefit in stress reduction for weight loss. Some well-controlled trials do support the use of ginkgo as a mild anxiolytic.78-80 One review81 described improvement in cerebral insufficiency and intermittent claudication in several studies. There is, however, no suggestion in the literature that the treatment of any of these conditions would affect weight loss.

Phenylpropanolamine
Phenylpropanolamine, or PPA, is a non-prescription product that appears to cause weight loss by central appetite suppression.82 There are, however, safety concerns associated with this product.83 Combined studies of PPA and PPA with caffeine give weight loss of 0.14 to 0.27 kilograms a week greater than that achieved with a placebo.84 The safety and efficacy of low-dose PPA, pseudoephedrine, and PPA with benzocaine in causing weight loss have been investigated in placebo-controlled studies in obese subjects.82 Two doses of PPA (12.5 milligrams three times a day and 75 milligrams a day) produced twice the weight loss of a placebo, but the difference was not statistically significant. Pseudoephedrine was no different from the placebo in inducing weight loss. The PPA-benzocaine group produced more adverse events than the benzocaine group (p = 0.03), the placebo group (p = 0.03) or the PPA group (p = 0.09), without additional weight loss.

Cellulite treatments
A 12-week randomised controlled trial assessed the effectiveness of two different treatments for cellulite85twice-daily application of aminophylline cream and twiceweekly treatment with Endermologie ES1. No difference was detected in thigh girth at two points and in thighfat depth measurement by ultrasound between active and placebo treatment or active and no treatment.

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10.1.3

Supplements with no scientific rationale and no acceptable evidence

A range of supplements for which there is no scientific rationale and no acceptable evidence are promoted. Grapeseed extract contains a class of antioxidants called proanthocyanids. These are added to some proprietary slimming products in the hope that they will have some effect on body fat, although there are no suggestions about the mechanism of action and there is no evidence of efficacy. Lecithin is a phospholipid involved in the digestion, absorption and transport of fat around the body. This has given rise to the idea that taking extra lecithin will keep fat moving around the body and prevent it being deposited in fat depots. There is, however, no biochemical basis for such a belief, so it is not surprising that there are no reported trials of lecithin for weight loss. It has been claimed that escin, a seed extract from the horse chestnut, aids circulation and prevents oedema. However, of over 300 entries in Medline, none refers to its effectiveness, or even potential effectiveness, in weight management. Isoflavones, which are phytoestrogens derived from soybeans and sweet clover, are often included in non-prescription weight-loss formulations. No studies have directly examined isoflavones and weight loss, and there is no sound theoretical suggestion that isoflavones would have any role in weight loss. Inositol is a phospholipid that can be made by the body from glucose. High concentrations are found in skeletal muscle, and this has made the substance popular as a supplement for people wishing to increase their lean body mass. One studyoften quoted by supplement sellersclaimed that inositol increased lean body mass, but the study was on four males and the results have not been published in the peer-reviewed literature. Nor is there any theoretical reason why inositol would be involved in weight loss. St Johns wort (Hypericum performatum) has long been used in alternative medicine. A 1996 meta-analysis of randomised clinical trials revealed that St Johns wort does possess clinically significant antidepressive effects.86 It appears to act like other antidepressant medications, although its exact mechanisms are not known. There are no suggestions in the literature (including the herbal literature) that hypericum has any effect on weight loss, nor have there been any studies demonstrating, or attempting to demonstrate, this effect.

A number of other substancesamong them milk thistle, collagen hydrolysate, citrin K, glycerine, aminogen, calcium pyruvate, potassium sorbate, sodium benzoate, and even demineralised waterhave also been used in weight-loss preparations, and the list is being added to constantly by eager marketers. There is no theoretical or practical rationale for the weight-loss effectiveness of any of these substances and there are no published data supporting their effectiveness either singly or in combination.
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10.1.4

Summary

There is a large number of weight-loss supplements on the non-prescription market and a high turnover of them. Most products are accompanied by a recommendation to adopt an energy-controlled diet plus exercise. If these recommendations are followed, they are likely to have at least a short-term weight-loss effectoften confused with the effectiveness of the product. Nevertheless, although there is no convincing evidence for any of these products, many have a plausible rationale and warrant further evaluation. It should also be noted that, while individual substances appear to lack effectiveness, the possible benefits of synergistic effects between ingredients cannot be ruled out. One placebocontrolled clinical study on a widely used product, Cellasene, which contains Ginkgo biloba, sweet clover, seaweed, grapeseed oil, lecithin, and evening primrose oil, found no effects of the product after two months.87 However, another natural dietary combination was found to accelerate the rate of fat loss during a four-week diet and exercise program.88 Similarly, a mixed herbal preparation containing yerba mat, guarana and damiana has been found to reduce body weight by 5.1 kilograms, compared with 0.3 kilograms with a placebo, over 45 days in healthy overweight subjects; the mix also helped maintain weight loss in a group of overweight subjects who continued the treatment for 12 months.89 A similar effect has been found in a 12-week randomised controlled trial with 40 obese subjects using a weight-reduction agent based on natural ingredients;90 there was a significant difference in weight reduction in favour of the active group (3.5 versus 1.2 kilograms), most of this reduction being due to fat loss. A herbal preparation known as Slimax has been marketed in Australia for several years and is claimed to reduce body weight. It appears to enhance lipolysis in animal studies.91 A six-week double-blind clinical trial in overweight and obese subjects has shown that a daily dose of about 40 milligrams dry weight of the preparation produced a significant 8.5 per cent decrease in body weight and an 8 per cent decrease in waist circumference. These differences were, however, not statistically significant when compared with the differences noted in the placebo group.92 Whilst the evidence for all of these products is not sufficient to warrant the products acceptance, continued evaluation is recommended. Evidence-based statement At present no non-prescription supplements have demonstrated sufficient evidence of long-term weight loss and lack of significant side effects. Recommendation: level D It is important to advise patients about the lack of evidence for the use of alternative, over-the-counter weight-loss medications and, in some cases, the possible dangers of their use. Evidence level Good quality evidence not available

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10.2

C O M M E R C I A L W E I G H T- L O S S P RO G R A M S

In the US 13 per cent of women and 5 per cent of men participate in organised weight-loss programs.93,94 There is some evidence in the literature of more successful weight loss with commercial programs compared with non-commercial programs, both when these programs were first introduced95 and more recently.96 However, few randomised controlled trials of commercial weight-loss programs have been carried out. One recent randomised controlled trial compared the effects of a self-help program (brief counselling and provision of printed materials) with a commercial program (Weight Watchers) on weight loss in overweight and obese men and women.96 After 26 weeks subjects in the commercial program had greater decreases in body weight (4.8 versus 1.4 kilograms) and waist circumference (4.3 versus 0.7 centimetres) compared with those in the self-help program. The short-term success of commercial programs has been ascribed to financial incentives and supportive group pressure. However, there is also some evidence of more successful long-term maintenance of weight loss from two recent studies. Lowe et al. have shown that five years following successful completion of a commercial weight-loss program (Weight Watchers) 43 per cent of subjects maintained a weight loss of 5 per cent of more and 19 per cent maintained a weight loss of at least 10 per cent.97 Similarly, Gosselin and Cote have shown that five to 11 years after women had participated in a popular commercial weight-loss program called Mincavi, based on Canadas Food Guide, 29 per cent maintained a weight loss of at least 5 per cent and 14 per cent maintained a weight loss of at least 10 per cent.98 Therefore, in some individuals commercial weight-loss programs can lead to effective weight maintenance long after the individuals have left the program. Long-term success has also been shown with a commercially based waist loss program in Caucasian99 and Indigenous Australian men,100 although these studies were not randomised and no controls were included. There is some evidence that people participating in commercial weight-loss programs have significantly higher rates of depressive symptomatology, psychosocial disability and body dissatisfaction compared with people seeking other forms of treatment.101,102 Programs that involve group supportWeight Watchers, for exampleare associated with psychological benefits and improved quality of life.103 These psychological changes may help motivate overweight people to maintain the physical activity and nutritional practices necessary to lose and maintain weight.

10.3

G A P S I N K N OW L E D G E

Supplements that are claimed to induce weight loss and to have a plausible mode of action warrant further evaluation with long-term randomised controlled trials. The synergistic effects between different components that can be found in these products would also be worth evaluating, although they are difficult to test. Good-quality randomised controlled trials of commercial weight-loss programs are also needed.

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REFERENCES
1 2 3 4 Blanck HM, Khan LK, Serdula MK. Use of nonprescription weight loss products: results from a multistate survey. JAMA 2001;286(8):9305. Egger G, Cameron-Smith D, Stanton R. The effectiveness of popular, non-prescription weight loss supplements. Med J Aust 1999;171:6048. Morelli V, Zoorob RJ. Alternative therapies. Part I: depression, diabetes, obesity. Am Fam Physician 2000;62(5):105160. Allison D, Fontaine KR, Heshka S, Mentore JL, Heymsfield SB. Alternative treatments for weight loss: a critical review. Crit Rev Food Sci Nutr 2001; 41(1):128. Rothacker DQ, Waitman BE. Effectiveness of a Garcinia cambogia and natural caffeine combination in weight loss: a double-blind placebo-controlled pilot study. Int J Obes 1997;21(suppl. 2):53. Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomised controlled trial. JAMA 1998;280(18):1596600. Badmaev V, Majeed M, Conte AA. Garcinia cambogia for weight loss. JAMA 1999;282(3):2334; discussion 235. Firenzuoli F, Gori L. Garcinia cambogia for weight loss. JAMA 1999;282(3):234; discussion 235. Mattes RD, Bormann L. Effects of (-)-hydroxycitric acid on appetitive variables. Physiol Behav 2000;71(12):8794. Kriketos AD, Thompson HR, Greene H, Hill JO. (-)-Hydroxycitric acid does not affect energy expenditure and substrate oxidation in adult males in a postabsorptive state. Int J Obes Relat Metab Disord 1999;23(8):86773. van Loon LJ, van Rooijen JJ, Niesen B, Verhagen H, Saris WH, Wagenmakers AJ. Effects of acute (-)-hydroxycitrate supplementation on substrate metabolism at rest and during exercise in humans. Am J Clin Nutr 2000;72(6):144550. Dodd SL, Herb RA, Powers SK. Caffeine and exercise performance. Sports Med 1993;15:(1):1423. Flinn S, Gregory J, McNaughton LR, Tristram S, Davies P. Caffeine ingestion prior to incremental cycling to exhaustion in recreational athletes. Int J Sports Med 1990;11:18893. Fredholm B. On the mechanism of action of theophylline and caffeine. Acta Med Scand 1985;217:14953. Anselme F, Collomp K, Mercier B, Ahmaidi S, Prefaut C. Caffeine increases maximal anaerobic power and blood lactate concentration. Eur J Appl Physiol 1992;65(2):18891. Cole KJ, Costill DL, Starling RD, Goodpaster BH, Trappe SW, Fink WJ. Effect of caffeine ingestion on perception of effort and subsequent work production. Int J Sport Nutr 1996;6(1):1423. Arciero PJ, Gardner AW, Calles-Escandon J, Benowitz NL, Poehlman ET. Effects of caffeine ingestion on NE kinetics, fat oxidation, and energy expenditure in younger and older men. Am J Physiol 1995;268(6 Pt 1):E1192E1198.
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Horton TJ, Geissler CA. Post-prandial thermogenesis with ephedrine, caffeine and aspirin in lean, pre-disposed obese and obese women. Int J Obes Relat Metab Disord 1996;20(2):917. Astrup A, Buemann B, Christensen NJ, Toubro S, Thorbek G, Victor OJ et al. The effect of ephedrine/caffeine mixture on energy expenditure and body composition in obese women. Metabolism 1992;41:6868. Astrup A, Toubro S, Cannon S, Hein P, Breum L, Madsen J. Caffeine: a double-blind, placebo-controlled study of its thermogenic, metabolic, and cardiovascular effects in healthy volunteers. Am J Clin Nutr 1990;51(5):75967. Arciero PJ, Gardner AW, Calles-Escandon J, Benowitz NL, Poehlman ET. Effects of caffeine ingestion on NE kinetics, fat oxidation, and energy expenditure in younger and older men. Am J Physiol 1995;286(6 Pt 1):E1192E1198. Graham TE, Rush JW, van Soeren MH. Caffeine and exercise: metabolism and performance. Can J Appl Physiol 1994;19(1):11138. Astrup A, Breum L, Toubro S, Hein P, Quaade F. 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. Int J Obes 1992;16:26977. Molnar D, Torok K, Erhardt E, Jeges S. Safety and efficacy of treatment with an ephedrine/caffeine mixture. The first double-blind placebo-controlled pilot study in adolescents. Int J Obes Relat Metab Disord 2000;24(12):15738. Boozer CN, Nasser JA, Heymsfield SB, Wang V, Chen G, Solomon JL. An herbal supplement containing ma huangguarana for weight loss: a randomized, double-blind trial. Int J Obes Relat Metab Disord 2001;25(3):31624. Haller C, Benowitz N. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. New Engl J Med 2000;343(25):18338. Gurley BJ, Gardner SF, White LM, Wang PL. Ephedrine pharmacokinetics after the ingestion of nutritional supplements containing Ephedra sinica (ma huang). Ther Drug Monit 1998;20(4):43945. Cannon ME, Cooke CT, McCarthy JS. Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products. Med J Aust 2001;174(10):5201. Han L-K, Takaku T, Kimura Y, H. O. Anti-obesity action of oolong tea. Int J Obes 1999;23:98105. Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr 1999;70(6):10405. Dulloo AG, Seydoux J, Girardier L, Chantre P, Vandermander J. Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity. Int J Obes Relat Metab Disord 2000;24(2):2528. Ormrod DJ, Holmes CC, Miller TE. Dietary chitosan inhibits hypercholesterolaemia and atherogenesis in the apolipoprotein E-deficient mouse model of atherosclerosis. Atherosclerosis 1998;138(2):32934.

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Nauss JL, Thompson JL, Nagyuvary J. The binding of micellar lipids to chitosan. Lipids 1983;18:71419. Ernst E, Pittler MH. A metaanalysis of chitosan for body weight reduction. Perfusion 1998;11:4615. Pittler MH, Abbot NC, Harkness EF, Ernst E. Randomized, double-blind trial of chitosan for body weight reduction. Eur J Clin Nutr 1999;53(5):37981. Ho SC, Tai ES, Eng PH, Tan CE, Fok AC. In the absence of dietary surveillance, chitosan does not reduce plasma lipids or obesity in hypercholesterolaemic obese Asian subjects. Singapore Med J 2001;42(1):610. Anderson RA. Chromium, glucose intolerance and diabetes. J Am Coll Nutr 1998;17(6):54855. Evans G. The effect of chromium picolinate on insulin controlled parameters in humans. Int J Biosoc Med Res 1989;11:16380. Kaats GR, Fischer JA. The effects of chromium picolinate supplementation on body composition in different age groups. Am Aging Assoc Abstr 1991;21:138. Anderson RA, Polansky MM, Bryden NA, Roginski EE, Mertz W, Glinsmann W. Chromium supplementation of human subjects: effects on glucose, insulin, and lipid variables. Metabolism 1983;32(9):8949. Campbell WW, Joseph LJ, Daver SL, Cyr-Campbell D, Anderson RA, Evans WJ. Effects of resistance training and chromium picolinate on body composition and skeletal muscle in older men. J Appl Physiol 1999;86(1):2939. Clancy SP, Clarkson PM, DeCheke ME, Nosaka K, Freedson PS, Cunningham JJ. Effects of chromium picolinate supplementation on body composition, strength and urinary chromium loss in football players. Int J Sports Med 1994;4:14253. Hallmark M, Reynolds TH, DeSouza CA, Dotson CO, Anderson RA, Rogers MA. Effects of chromium and resistive training on muscle strength and body composition. Med Sci Sports Exerc 1996;28(1):13944. Lukaski HC, Bolonchuk WW, Siders WA, Milne DB. Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men. Am J Clin Nutr 1996;63(6):95465. Trent LK, Thieding-Cancel D. Effects of chromium picolinate on body composition. J Sports Med Phys Fitness 1995;35(4):27380. Lukaski HC. Magnesium, zinc, and chromium nutriture and physical activity. Am J Clin Nutr 2000;72(2 suppl.):585S593S. Walker LS, Bemben MG, Bemben DA, Knehans AW. Chromium picolinate effects on body composition and muscular performance in wrestlers. Med Sci Sports Exerc 1998;30(12):17307. Crawford V, Scheckenbach R, Preuss HG. Effects of niacin-bound chromium supplementation on body composition in overweight African-American women. Diab Obes Metab 1999;1(6):3317. Grant K, Chandler RM, Castle AL, Ivy JL. Chromium and exercise training: effect on obese women. Med Sci Sports Exerc 1997;29(8):9928. Pasman W, Westerterp-Plantenga MS, Saris WH. The effectiveness of long-term supplementation of carbohydrate, chromium, fibre and caffeine on weight maintenance. Int J Obes 1997;21(12):114351.
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Cerulli J, Grabe DW, Gauthier I, Malone M, McGoldrick MD. Chromium picolinate toxicity. Ann Pharmacother 1998;32(4):42831. Buck SH, Burks TF. The neuropharmacology of capsaicin: review of some recent observations. Pharmacol Rev 1986;38(3):179226. MacLean DB. Abrogation of peripheral cholecystokinin-satiety in the capsaicin treated rat. Regul Pept 1985;11(4):32133. Watanabe T, Kawada T, Kurosawa M, Sato A, Iwai K. Adrenal sympathetic efferent nerve and catecholamine secretion excitation caused by capsaicin in rats. Am J Physiol 1988;255(1 Pt 1):E23E27. Wahlqvist ML, Wattanapenpaiboon N. Hot foodsunexpected help with energy balance? Lancet 2001;358(9279):3489. Debreceni A, Abdel-Salam OM, Figler M, Juricskay I, Szolcsanyi J, Mozsik G. Capsaicin increases gastric emptying rate in healthy human subjects measured by 13C-labeled octanoic acid breath test. J Physiol Paris 1999;93(5):45560. Yoshioka M, St-Pierre S, Drapeau V, Dionne I, Doucet E, Suzuki M et al. Effects of red pepper on appetite and energy intake. Br J Nutr 1999;82(2):11523. Yoshioka M, Doucet E, Drapeau V, Dionne I, Tremblay A. Combined effects of red pepper and caffeine consumption on 24 h energy balance in subjects given free access to foods. Br J Nutr 2001;85(2):20311. Yoshioka M, St-Pierre S, Suzuki M, Tremblay A. Effects of red pepper added to high-fat and high-carbohydrate meals on energy metabolism and substrate utilization in Japanese women. Br J Nutr 1998;80(6):50310. Matsumoto T, Miyawaki C, Ue H, Yuasa T, Miyatsuji A, Moritani T. Effects of capsaicin-containing yellow curry sauce on sympathetic nervous system activity and diet-induced thermogenesis in lean and obese young women. J Nutr Sci Vitaminol (Tokyo) 2000;46(6):30915. Cameron-Smith D, Colquhoun EQ, Ye JM, Hettiarachchi M, Clark MG. Capsaicin and dihydrocapsaicin stimulate oxygen consumption in the perfused rat hindlimb. Int J Obes 1990;14(3):25970. Edwards SJ, Montgomery IM, Colquhoun EQ, Jordan JE, Clark MG. Spicy meal disturbs sleep: an effect of thermoregulation? Int J Psychophysiol 1992;13(2): 97100. Glickman-Weiss E, Hearon CM, Nelson AG, Nelson AG, Day R. Does capsaicin affect physiologic and thermal responses of males during immersion in 22 degrees C? Aviat Space Environ Med 1998;69(11):10959. Heinonen O. Carnitine and physical activity. Sports Med 1996;22(2):10914. Vukovich M, Costill DL, Fink WJ. Carnitine supplementation: effect on muscle carnitine and glycogen content during exercise. Med Sci Sports Exerc 1994;26(9):11229. Sulkers EJ, Lafeber HN, Degenhart HJ, Przyrembel H, Schlotzer E, Sauer PJ. Effects of high carnitine supplementation on substrate utilization in low-birthweight infants receiving total parenteral nutrition. Am J Clin Nutr 1990;52(5): 88994. Villani RG, Gannon J, Self M, Rich PA. L-carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women. Int J Sport Nutr Exerc Metab 2000;10(2):199207.
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Livesey G. Fibre as energy in man. In: Kritchevsky D, ed. Dietary fibre in health and disease. Minnesota: Eagan Press, 1995:4657. Tiwary CM, Ward JA, Jackson BA. Effect of pectin on satiety in healthy US Army adults. J Am Coll Nutr 1997;16(5):4238. Matzkies F, Budelski I, Webs B. Effect of a fiber-containing dietary formula on metabolism. Fortschr Med 1982;100(19):91720. Pasman WJ, Westerterp-Plantenga MS, Muls E, Vansant G, van Ree J, Saris WH. The effectiveness of long-term fibre supplementation on weight maintenance in weight-reduced women. Int J Obes 1997;21(7):54855. Catellanos V, Rolls B. Diet composition and the regulation of food intake and body weight. In: Dalton S, ed. Overweight and weight management. Galthersburd, MD: Aspen Publications, 1997. Pittler MH, Ernst E. Guar gum for body weight reduction: meta-analysis of randomized trials. Am J Med 2001;110(9):72430. Konno N, Makita H, Yuri K, Iizuka N, Kawasaki K. Association between dietary iodine intake and prevalence of subclinical hypothyroidism in the coastal regions of Japan. J Clin Endocrinol Metab 1994;78(2):3937. Shilo S, Hirsch HJ. Iodine-induced hyperthyroidism in a patient with a normal thyroid gland. Postgrad Med J 1986;62(729):6612. Marcilhac A, Dakine N, Bourhim N, Guillaume V, Grino M, Drieu K. Effect of chronic administration of Ginkgo biloba extract or Ginkgolide on the hypothalamicpituitaryadrenal axis in the rat. Life Sci 1998;62(25):232940. Wing R. Behavioral approaches to the treatment of obesity. In: Bray GA, Bouchard C, James WPT, eds. Handbook of obesity. New York: Marcel Dekker, 1998:85574. Porsolt RD, Martin P, Lenegre A, Fromage S, Drieu K. Effects of an extract of Ginkgo biloba (EGB 761) on learned helplessness and other models of stress in rodents. Pharmacol Biochem Behav 1990;36(4):96371. Rapin JR, Lamproglou I, Drieu K, De Feudis FV. Demonstration of the anti-stress activity of an extract of Ginkgo biloba (EGb761) using a discrimination learning task. Gen Pharmacol 1994;25(5):100916. White H, Scates PW, Cooper BR. Extracts of Ginkgo biloba leaves inhibit monoamine oxidase. Life Sci 1996;58(16):131521. Garg R, Nag D, Agrawal A. A double blind placebo controlled trial of Ginkgo biloba extract in acute cerebral ischaemia. J Assoc Physicians India 1995;43 (11):7603. Greenway F, Herber D, Raum W, Morales S. Double-blind, randomized, placebo-controlled clinical trials with non-prescription medications for the treatment of obesity. Obes Res 1999;7(4):3708. Fillmore CM, Bartoli L, Bach R, Park Y. Nutrition and dietary supplements. Phys Med Rehabil Clin N Am 1999;10(3):673703. Greenway FL. Clinical studies with phenylpropanolamine: a metaanalysis. Am J Clin Nutr 1992;55(1 suppl.):203S205S. Collis N, Elliot LA, Sharpe C, Sharpe DT. Cellulite treatment: a myth or reality. A prospective randomized, controlled trial of two therapies, Endermologie and aminophylline cream. Plast Reconstr Surg 1999;104(4):111014; discussion 111517.
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Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D. St Johns wort for depressionan overview and meta-analysis of randomised clinical trials. BMJ 1996;313:2538. Lis-Balchin M. Parallel placebo-controlled clinical study of a mixture of herbs sold as a remedy for cellulite. Phytother Res 1999;13(7):6279. Hoeger WW, Harris C, Long EM, Hopkins DR. Four-week supplementation with a natural dietary compound produces favorable changes in body composition. Adv Ther 1998;15(5):30514. Andersen T, Fogh J. Weight loss and delayed gastric emptying following a South American herbal preparation in overweight patients. J Hum Nutr Diet 2001;14(3):24350. Thom E. A randomized, double-blind, placebo-controlled trial of a new weight-reducing agent of natural origin. J Int Med Res 2000;28(5):22933. Wijaya E, Wu Z-M, Ng F. Effect of Slimax, a Chinese herbal mixture, on obesity. Int J Pharmacognosy 1995;33:416. Ignjatovic V, Ogru E, Heffernan M, Libinaki R, Lim Y, Ng F. Studies on the use of Slimax, a Chinese herbal mixture, in the treatment of human obesity. Pharmaceut Biol 1999;37:16. Levy AS, Heaton AW. Weight control practices of US adults trying to lose weight. Ann Intern Med 1993;119(7 Pt 2):6616. Latner J. Self-help in the long-term treatment of obesity. Obes Rev 2001;2:8797. Williams AE, Duncan B. A commercial weight-reducing organization: a critical analysis. Med J Aust 1976;1(21):7815. Heshka S, Greenway F, Anderson JW, Atkinson RL, Hill JO, Phinney SD et al. Self-help weight loss versus a structured commercial program after 26 weeks: a randomized controlled study. Am J Med 2000;109(4):2827. Lowe MR, Miller-Kovach K, Phelan S. Weight-loss maintenance in overweight individuals one to five years following successful completion of a commercial weight loss program. Int J Obes Relat Metab Disord 2001;25(3):32531. Gosselin C, Cote G. Weight loss maintenance in women two to eleven years after participating in a commercial program: a survey. BMC Womens Hlth 2001;1(1):2. Egger G, Bolton A, ONeill M, Freeman D. Effectiveness of an abdominal obesity reduction program in men: the GutBusters waist loss program. Int J Obes 1996;20:22735. Egger G, Fisher G, Piers S, Bedford K, Morseau G, Sabasio S. Abdominal obesity reduction in indigenous men. Int J Obes Relat Metab Disord 1999;23(6):5649. Goldstein LT, Goldsmith SJ, Anger K, Leon AC. Psychiatric symptoms in clients presenting for commercial weight reduction treatment. Int J Eat Disord 1996;20(2):1917. Cash TF. Body-image attitudes among obese enrollees in a commercial weightloss program. Percept Mot Skills 1993;77(3 Pt 2):1099103. Miller-Kovach K, Hermann M, Winick M. The psychological ramifications of weight management. J Womens Hlth Gend Based Med 1999;8(4):47782. UK Foods Standards Agency. Safe Upper Levels for Vitamins and Minerals. Available at: http://www.foodstandards.gov.uk/ouradvisors/vitandmin/120281
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