Obesity practically defines the human condition in developed countries, and increasingly in developing ones throughout the world. The incidence and prevalence of weight issues and obesity continues to become problematic both for individuals and society.1^,2^,3 In the US alone, annual health care costs associated with weight problems and obesity total between $93 billion and $117 billion.4^,5 Obesity has therefore become a challenge for public health professionals, doctors, researchers and scientists—not to mention, of course, overweight individuals.

Although the energy-balance equation in weight maintenance seems straightforward, individuals have difficulty succeeding at weight-loss outside of an experimental, supervised design, and few can successfully maintain it long-term.6^,7 Diet management and adequate exercise are critical to any sustained weight loss and maintenance program; however, they are apparently often not enough. Functional foods and dietary supplements may prove useful as adjunctive support in helping to maintain weight management and in the prevention and treatment of weight problems and obesity.

The following is a selective review of potentially useful nutrients in the fight against obesity, including an analysis of the current research regarding dietary calcium, diacylglycerols, conjugated linoleic acid, green tea extract/epigallocatechin gallate (EGCG), L-carnitine and artificial sweeteners. All of these are currently available to manufacturers and consumers and are being marketed as anti-obesity agents with weight-loss potential.

Calcium
One of the newest areas of obesity and weight-loss research to emerge in the past few years involves dietary calcium and its possible effect on body mass index (BMI), body composition, weight loss and weight regulation.8^,9^,10

Calcium intake was first correlated with body weight reduction as a secondary outcome in hypertension studies conducted 20 years ago.11 Longitudinal observations of calcium intake as a predictor of obesity fuelled greater interest, and today calcium is widely accepted as a critical modulator of chronic disease.12 In particular, high calcium intake can help lower blood pressure, favourably alter lipid profiles and prevent cardiovascular disease, and regulate body weight to both prevent and treat obesity.8^,13^,14

To date, numerous studies have been conducted in the animal model that concludes that high intakes of dietary calcium can prevent weight gain, maximise lean body mass, and facilitate weight loss. Repeated studies indicate a substantially greater effect when diets are rich in dairy products as opposed to calcium supplementation (See "State Of The Science" sidebar, below). At the cellular level, calcium-rich diets attenuate obesity by minimising adipocyte lipid accretion and weight gain during periods of overconsumption and by increasing lipolysis and preserving thermogenesis during periods of hypocaloric intake, markedly accelerating weight loss.8^,10^,11^,12^,14

There are currently few published studies specifically designed to assess the role of calcium for weight loss in humans, though some have been completed. However, re-evaluation of studies designed to test hypertension or skeletal endpoints support the results from the animal model: High intakes of calcium-rich dairy products protect against obesity, enhance weight and fat loss in conjunction with caloric restriction, increase or preserve lean body mass, and significantly reduce abdominal adiposity.10^,11^,12^,13^,14 Increased dairy consumption also has a strong inverse association with insulin-resistance syndrome (obesity, glucose intolerance, hypertension, dyslipidaemia) and may reduce the risk of Type 2 diabetes and cardiovascular disease.15^,16

Many studies demonstrate high calcium/kcal intake to be a negative predictor of body weight and fat gain.17 Individuals with the lowest calcium intakes have the highest body weights, per cent body fat (per cent BF), fat mass (FM), BMI, waist circumference, and total abdominal adipose tissue,12^,18^,19^,20 whereas those with the highest intakes are leaner and weigh less. These findings prompted one researcher to predict a weight decrement of 8.2 kg for every calcium intake increment of 1,000mg, confirmed by population data.17

This is not to say that every analysis of calcium as an anti-obesity agent has been positive. A review by Barr found only one study out of 17 for calcium supplementation that resulted in weight loss, though the studies evaluated were not designed to reduce body weight or fat mass.21 Likewise, while Norwegian investigators found calcium intake and BMI to be positively correlated in men but not in women, authors cite flaws in study design and recommend cautious interpretation of their data.²² Large clinical trials to assess the effects of supplemental calcium and other components of dairy products on body weight will help clarify this apparent relationship.

Diacylglycerols
Diacylglycerols (DAGs) have shown tremendous promise in clinical trials to benefit lipid metabolism and could make a strong showing in the US market. DAG oil is currently sold in Japan as ?Healthy Econa Cooking Oil? (Kao corporation), and is being test-marketed in the Atlanta and Chicago US markets as Enova. Several double-blind, controlled studies on DAG in humans have elicited promising results for CVD risk and weight control.23 Specifically, DAG oil has been associated with decreased postprandial serum and chylomicron triglycerides,24^,25 decreased serum HbA1c, increased fat oxidation,26 decreased body fat accumulation and decreased visceral fat,27^,28^,29^,30 enhanced weight loss,31 and decreased appetite and desire to eat,26 all of which factor importantly into the management of obesity.

Diacylglycerol is a natural component (2?10 per cent) of various edible oils and is present in the diet in very small concentrations.31 Recent studies illustrate beneficial effects on lipid metabolism and energy balance when DAG is partially substituted for TAG traditionally found in the diet. TAG is the form in which most fats are consumed. They carry three fatty acids on a glycerol backbone molecule. DAGs carry two fatty acids in the first and second positions on the backbone (1,2 DAGs) or in the first and third positions (1,3 DAGs).

In one randomised, double-blind, parallel intervention trial, 131 men and women consumed either DAG or TAG incorporated into food products in conjunction with a reduced-energy deficit diet for 24 weeks. The oil used (Econa Oil, Kao Corporation, Biological Science Laboratories, Tochigi, Japan) was prepared from rapeseed oil (canola) in a process that turned approximately 90 per cent of the fat into DAG by weight, with a 3?to?7 ratio of 1,2-diacylglycerol to 1,3-diacylglycerol. Doses varied according to individual caloric needs for weight loss to supply about 15 per cent of the total dietary energy from either DAG or TAG oil. At all time points during the study after randomisation, both mean body weight loss and mean fat loss were greater in the DAG oil (?3.6 per cent and ?8.3 per cent, respectively) group than the TAG oil group (?2.5 per cent and ?5.6 per cent, respectively).31

Similarly, another study examined the effects of long-term ingestion (16 weeks) of DAG in a double-blind controlled study of 38 men. Again, the DAG group lost significantly more weight than the TAG group (?2.6 ? 0.3 kg vs. ?1.1 ? 0.4 kg) and reduced both waist circumference and BMI over the TAG group. In addition, the DAG group lost more body fat, total fat, visceral fat, subcutaneous fat and hepatic fat, all measured via computed tomography.27

More recently, diacylglycerol oils (80 per cent DAG by weight, 65-70 per cent in 1,3-DAG form, Healthy Econa brand oil, Kao Corporation) have been shown to reduce appetite, feelings of hunger and desire to eat, perhaps due to the increase in fat oxidation and with important implications for body-weight control.26

Conjugated Linoleic Acid
Since its isolation from grilled meat and the subsequent demonstration in the late 1980s of its anti-carcinogenic properties, conjugated linoleic acid (CLA) has been heavily scrutinised.32 CLA is a collective term for the mixture of naturally occurring positional and geometric isomers of linoleic acid with conjugated double bonds and is perhaps the most controversial potential anti-obesity agent.33

There are many possible isomers of CLA. The predominant dietary isomer of CLA is cis9, trans 11, formed by the bacteria of ruminants and found primarily in meat and dairy products.34 Most of the CLA supplements studied and available as supplements for human consumption contain a mixture of isomers that are approximately 30?40 per cent each of the c9,t11 and the t10,c12, though significant recent developments indicate a need for isomer-specific studies to evaluate isomer-specific mechanisms.33

CLA isomers have been shown to modulate immune function,32 alter markers of atherosclerosis,35 and modify risk of obesity and diabetes.36^,37 Of the numerous studies conducted on CLA as an anti-obesity agent, the most compelling and consistent research thus far is in the animal model, where feeding mixed isomers has been shown to attenuate obesity, particularly through minimised fat accretion, decreased fat mass and increased lean body mass.38^,39^,40 This is especially true during periods of growth and maturation, though effects also depend on species, age, gender, and most importantly, CLA isomer composition.40^,41^,42^,43 Interestingly, weight loss is not a consistent result of CLA supplementation even in the animal model,44 though some studies demonstrate rapid and significant weight loss.45 The most recent studies in mice and hamsters credit t-10,c-12, as opposed to c-9,t-11, for minimising weight gain and reducing body fat.33^,43^,44

Despite the trend of positive body composition data from the animal model, human studies offer inconsistent and inconclusive results.32^,33 While some favourably link CLA to decreases in adipocyte fat accumulation, few show CLA to enhance weight loss, and some indicate a dyslipidaemic effect from CLA supplementation.33^,46^,47 In fact, recent research urges caution regarding CLA as an anti-obesity supplement for humans, as data are not only conflicting but new evidence suggests unfavourable and clinically significant adverse effects including oxidative stress, insulin sensitivity and cardiovascular disease.33^,46^,47

So far, human studies on CLA as a weight-loss or fat-loss agent have shown substantial differences in study design, including major differences in study duration, subject characteristics, CLA-isomer composition, and dosage and even measurement methods and reporting of parameters. 32^,33 Without uniformity, each study has been interpreted individually. It is fair to say, however, that most do not show any changes in body weight, and few show changes in body composition. Of 11 studies greater than four weeks duration and published in peer-reviewed journals, none resulted in weight loss, only three found a decrease in fat mass and only one found a slight increase in fat-free mass (assumed to correspond to lean body mass). In trying to translate animal studies into a human model, it is important to note that the doses used in human studies (25?80mg/kg/day) can be anywhere from 1/10 to 1/50 of the amounts used in animals. Efficacious doses used in rats, for example, correlate to 130g CLA/day in humans. 33 [For an update on the expanding body of literature on CLA, go to www.wisc.edu/fri/clarefs.htm.]

Specific attention should be paid to the one study that directly measured insulin sensitivity.47 In a double-blind, placebo-controlled, 12-week trial of 60 obese men, 3.4 g/day of purified (75 per cent) t10,c12 CLA markedly increased 8-iso-PGF 2-alpha (578 per cent), a marker of non-enzymatic lipid peroxidation in vivo (essentially a marker of increased oxidative stress), and C-reactive protein (110 per cent), a marker of inflammation and strong predictor of cardiovascular disease. This study confirms an earlier study that demonstrates that t10,c12 isomer induces insulin resistance and suggests an intervention-mediated correlation between oxidative stress and impaired insulin sensitivity.46 Ironically, the isomer now thought to be most influential for favourable changes in body composition has also been linked to significant adverse effects that could seriously harm individuals most likely to be attracted to CLA supplementation—those with obesity and susceptibility to Type 2 diabetes.33

This is not the only study to uncover these alarming results. Several animal studies also document t10,c12-CLA-induced hyperinsulinaemia, insulin resistance and lipodystrophy.48^,49^,50 Yet, in sharp contrast, studies with mixed CLA isomers have shown reversal of insulin resistance in rodents37 and favourable alterations in several metabolic variables in human subjects with Type 2 diabetes.33 Again, these paradoxical findings are most likely the result of differences in isomer composition and dose, as well as species studied and metabolic status of the experimental model. Much further study is needed regarding individual isomers and dose specifications to reach an accurate and reproducible conclusion regarding CLA as an anti-obesity agent in humans.

Epigallocatechin Gallate (EGCG)
Epigallocatechin gallate (EGCG) constitutes greater than or equal to 50 per cent of the total catechins in tea and is widely accepted as the most pharmacologically active tea catechin.51 Many studies have shown that tea polyphenols can afford protection against diseases such as cancer,53^,54 coronary artery disease, stroke,52^,55 osteoporosis and obesity.56^,57 As a potentially thermogenic plant extract, much interest has been directed toward EGCG as an anti-obesity agent.58^,59 Like research with CLA, however, replicating results from animal models in human trials has been difficult, largely due to differences in experimental protocol, particularly with dose and method of delivery, and because the science is still evolving. Unlike CLA, however, EGCG has not been associated with potential cardiovascular risks—or any other risks.

Studies thus far suggest that both green tea and EGCG can lower serum and LDL cholesterol,60 increase HDL cholesterol, and lower serum glucose.51^,57 EGCG also has been shown to enhance weight loss, decrease BF,58 increase thermogenesis and fat oxidation,59^,61^,62 and modulate adipocyte function.51^,63 At this time, there are only a couple of studies in the published literature designed to specifically assess EGCG intake and weight/fat loss in humans. One study with a very small cohort (ten men) suggests supplementation with green tea extract (50mg caffeine + 90mg EGCG three times a day; AR25, Exolise, Arkopharma Laboratories, Nice, France) increases energy expenditure (EE) and decreases respiratory quotient (RQ) more than the same amount of caffeine or placebo.59

This suggests that green tea extract has thermogenic properties that promote fat oxidation beyond that of caffeine alone, and the study?s authors credit the combination of caffeine and EGCG for the EE effect. Because this was also a short-term study and all measurements were done during three separate occasions in a respiratory chamber, there are no changes in body weight or body composition to report. A study with oolong tea also suggests a metabolic boost from tea consumption but attributes the increase in EE to the caffeine. In that study, caffeine alone produced a greater effect on EE than did the oolong tea, which contains less EGCG than green tea extract. 61

Although some studies have demonstrated substantial, acute and rapid weight loss in rats given EGCG,58 the studies followed protocols that would be impractical in humans. For example, rapid weight loss was achieved in rats given very large doses of EGCG (30?100mg EGCG/kg body weight/day) as intra-peritoneal injections. As context, EGCG is thought to be poorly absorbed in the gastrointestinal tract, hence the interest in intravenous delivery.64 Human doses of comparable amounts would be 2,100?7,000mg EGCG/day for a 70kg man. This seems an impractical consideration for the human model. Of note, weight loss in the rats was reversed when administration of EGCG ceased.

To date, only one study, involving only ten subjects, suggests 270mg EGCG/day stimulates thermogenesis in lean and overweight humans.59 Until further investigation of EGCG on long-term energy balance and substrate utilisation occurs, it is difficult to calculate realistic and effective dosing requirements.

L-carnitine
Because of its role in fatty-acid oxidation, L-carnitine has caused much speculation as to its possible role as an ergogenic aid and as a potential mediator of fatty acid metabolism. However, it is difficult to assess its value as a weight-loss supplement because few human studies have been designed to evaluate that end.65

Indeed, no studies in the peer-reviewed literature demonstrate L-carnitine as an effective weight-loss aide in humans.65^,66 Much of the research available with human data has assessed L-carnitine in exercise performance, substrate utilisation, and metabolic markers of exercise stress and recovery.67 While some studies have investigated L-carnitine in combination with other nutrients (choline, caffeine) on fat metabolism, body fat and serum leptin, it is not possible to attribute specific positive effects, if any, to L-carnitine alone.68^,69 For example, one group of researchers examined carnitine and choline supplementation along with exercise in 19 healthy young women. The results, like those from a study in rats that also included caffeine, suggest a decrease in body fat and serum leptin comparable to mild exercise, yet cannot attribute the loss to L-carnitine alone because the intervention also included supplementation with choline and exercise.68 Some animal studies do show favourable effects of L-carnitine on body weight and body composition, yet others show no benefit.65^,66^,69^,70

One double-blind study was designed specifically to explore the efficacy of L-carnitine supplementation and weight loss in humans.65 It found no change in total body mass, fat mass or resting lipid utilisation between the L-carnitine and placebo groups. There was a significant and equal increase in resting energy expenditure (REE) for all subjects attributable to the exercise intervention, but with no difference between the two groups. Of note, five of the L-C group experienced nausea and diarrhoea with L-C supplementation (2g twice daily). Further studies are needed to elucidate what relationship might exist between L-C supplementation and weight loss.

Artificial Sweeteners
Despite their widespread use in foods and supplements for several decades, there is still no consensus regarding the usefulness of substituting artificial sweeteners for sucrose to regulate body weight or enhance weight loss. Considering the effect of the obesity epidemic and the relationship of high-energy diets and overconsumption, determining the effect of non-caloric sugar substitutes is important.

In a quest to answer just that, investigators in Denmark designed a long-term (ten-week) study to evaluate the effect of sucrose vs. artificially sweetened foods and beverages on weight control in 41 obese subjects.71 After ten weeks of supplementation, body weight and fat mass increased in the sucrose group by 1.6 and 1.3 kg, respectively, and decreased in the sweeteners group by 1.0 kg and 0.3 kg, respectively. In addition to weight gain, the sucrose group also experienced an increase in both systolic and diastolic blood pressure, whereas the sweeteners group enjoyed a decrease in both. Changes in blood pressure were related to changes in body weight, changes in sucrose intake, changes in energy intake and total energy.

The results of this study, while in favour of sweeteners, hardly close the debate. To the contrary, even the study investigators were surprised by the results, expecting instead to find further evidence that ingesting sweeteners increases body weight whereas ingesting sucrose decreases body weight, as proposed by numerous other studies.72^,73^,74

Although several investigators conclude that sweeteners do not increase appetite and can enhance weight loss and help to minimise weight gain,75^,76^,77^,78 others show that people who regularly consume artificial sweeteners in favour of sucrose weigh more and have higher body fat and BMI. An eight-year longitudinal study in France concluded that regular consumers of artificially sweetened products had higher body weight, body mass index, triglycerides and hyperglycaemia than non-users.72 To an uncritical eye, these findings may suggest a causal relationship between consuming artificial sweeteners and becoming overweight, yet a more likely scenario is that the subjects were already overweight and therefore chose artificial sweeteners for caloric reduction to enhance weight loss.

Foods Play The Heavy
While this review may have resulted in as many questions as answers, it is important to remember that what is shown to be metabolically efficacious in reducing weight in a controlled study will not always be behaviourally applied. Part of the science of building better foods must consider human nature. Product marketing should address the multi-faceted approach needed to successfully combat the obesity epidemic, along with documented, repeated, attendant human clinical trials proving product efficacy and safety. There is no magic bullet, though there are promising adjunctive therapies to diet and exercise. The synergies among laboratory testing, safety and everyday living will be paramount in the design of functional foods that are successful in addressing obesity worldwide.

Anne-Marie Nocton, MS, MPH, RD, is a nutrition consultant and advocate specializing in obesity prevention. She formerly directed nutrition research studies at the University of Tennessee.

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