Japanese researchers at the House Wellness Foods Corporation have been experimenting for several years with mixtures of caffeine and glucosylhesperidin, to find ways of speeding up fat loss with no side effects. So far the Japanese have only published animal studies, but recently they published the first human study on the slimming effect of the caffeine-glucosylhesperidin combination.
Glucosylhesperidin – or G-hesperidin – is a semi-synthetic compound. Chemists make the stuff by extracting hesperidin from citrus fruit peel, and then attaching it to the carbohydrate dextrin. [Structural formula shown below.]
Going by the patents, glucosylhesperidin is thousands of times more soluble than hesperidin, and so more likely to be more easily absorbable. And that makes glucosylhesperidin an interesting substance for supplements manufacturers.
Animal studies have shown that glucosylhesperidin reinforces the slimming effect of caffeine. Hesperidin, the natural analogue of glucosylhesperidin, reinforces the slimming effect of synephrine. Korean research has shown that hesperedin, the basic flavonoid in hesperidin, may also have a muscle strengthening effect. So you may see glucosylhesperidin cropping up in all kinds of bodybuilding and slimming supplements available online.
The Japanese divided 75 subjects on the plump side, with a BMI of 24-30, into five groups. Over a period of twelve weeks one group took a placebo and four other groups took supplements which supplied them with a daily 500 mg glucosylhesperidin.
One of the supplements groups got only glucosylhesperidin. The subjects in the three other supplements groups took in addition to the glucosylhesperidin also 25, 50 or 75 mg caffeine.
At the end of the 12 weeks, the subjects who had taken 500 mg glucosylhesperidin and 75 caffeine daily had lost fat. This supplement combination led above all to a reduction of subcutaneous fat.
The subjects who had taken 500 mg glucosylhesperidin and 75 mg caffeine lost a total of 1.43 kg weight. Four weeks later the weight had remained off.
The subjects did not change their diet. They also didn’t do any more exercise than they already did. No side effects were observed.
“Our results showed that intake of a combination of 500-mg G-hesperidin and 75-mg caffeine for 12 weeks significantly reduced abdominal fat (especially subcutaneous fat), body weight […] in subjects with a moderately high BMI”, the researchers wrote. “Therefore, a combination of G-hesperidin and caffeine may be useful for the prevention or treatment of obesity.”
Oral intake of a combination of glucosyl hesperidin and caffeine elicits an anti-obesity effect in healthy, moderately obese subjects: a randomized double-blind placebo-controlled trial
We have previously shown that a combination of glucosyl hesperidin (G-hesperidin) plus caffeine reduces accumulation of body fat, whereas G-hesperidin or caffeine alone shows little effect on high-fat diet-induced obesity in mice. The aim of this study is to evaluate the anti-obesity effect of G-hesperidin plus caffeine on body fat and serum TG in healthy subjects with moderately high body mass index (BMI) and serum TG. Since we considered that there are individual differences in caffeine sensitivity, we conducted dose-finding study of caffeine combined with G-hesperidin.
Seventy-five healthy subjects with moderately high BMI (24–30 kg/m2) and serum TG (100–250 mg/dl) were divided and assigned to 12-week intervention with daily intakes of 500 mg of G-hesperidin with or without 25, 50, or 75 mg of caffeine, or placebo in a randomized double-blind placebo-controlled design .
After intervention, decreases in abdominal fat area (AFA), especially subcutaneous fat area (SFA), were significantly greater in the G-hesperidin with 50-mg caffeine group (AFA:-8.4?±?21.9 v.s. 16.3?±?34.1 cm2; p?< ?0.05, SFA: -9.3?±?17.1 v.s. 11.2?±?18.3 cm2; p?0.01) and in the G-hesperidin with 75-mg caffeine group (AFA:-17.0?±?31.4 v.s. 16.3?±?34.1 cm2; p?0.01, SFA: -12.4?±?18.7 v.s. 11.2?±?18.3 cm2; p?0.01) than in the placebo group. Fat-decreasing effects of G-hesperidin were enhanced dose-dependently by caffeine addition. BMI decreases were significantly greater in the G-hesperidin with 75-mg caffeine group than in the placebo group (-0.56?±?0.74 v.s. -0.02?±?0.58 kg/m2; p?0.05). G-hesperidin with/without caffeine had no effect on serum TG (p?>?0.05 v.s. placebo).
These data suggested that a combination of 500-mg G-hesperidin with 50- or 75-mg caffeine may be useful for the prevention or treatment of obesity.
Prevalence of obesity continues to increase worldwide, mainly as a result of changing lifestyles. It is known that visceral fat-type obesity induces type-2 diabetes mellitus, hyperlipidaemia, hypertension and increases the risk of cardiovascular disease [1–3]. Subcutaneous fat-type obesity is associated with excessive weight gain, and is thought to be the main risk factor for osteoarthritis of the knee [4–7], sleep apnoea , and menstrual abnormalities [9–11]. Consequently, research on the prevention and treatment of obesity has been expanded.
Glucosyl hesperidin (G-hesperidin) is synthesized by enzymatic means from hesperidin purified from oranges (Citrus aurantium) and dextrin. Its solubility in water is over 10,000-fold greater than that of hesperidin . G-hesperidin has been reported to reduce serum levels of triglyceride (TG) in animals [13–15] and subjects with hypertriglyceridemia [16, 17]. The mechanism of the TG-lowering effect of G-hesperidin is thought to be down-regulation of the synthesis/secretion of very-low-density lipoprotein in hepatocytes , inhibition of lipogenesis, and induction of beta oxidation of fatty acids in high-fat diet-fed rats . Studies have shown that daily intake of G-hesperidin (500 mg) in subjects with a moderately high BMI for 12 weeks decreases abdominal fat significantly during the period, but these decreases do not differ significantly from those of subjects taking a placebo . Therefore, the anti-obesity effect of G-hesperidin is incompletely understood.
Caffeine is one of the most widely consumed dietary components (e.g., tea, coffee) with pharmacological effects and psychostimulant activity. Caffeine has been reported to induce lipolysis of adipocytes , fat oxidation , energy expenditure  and thermogenic responses  in humans. However, caffeine has not been shown to reduce body fat in humans, so its effects upon fat metabolism are, in general, considered to be insignificant .
We have shown before that combining food ingredients involved in lipid metabolism is useful for the prevention or treatment of obesity. For example, a mixture of thiamine, L-arginine, caffeine, and citric acid has been shown to have an anti-obesity effect in obese mice and humans with a high BMI [25, 26]. We have also shown that a combination of G-hesperidin and caffeine reduces accumulation of body fat through (at least in part) inhibition of hepatic lipogenesis, whereas G-hesperidin or caffeine alone show little effect on high-fat diet-induced obesity in mice .
We conducted an exploratory trial to investigate the anti-obesity effects of a combination of G-hesperidin and caffeine in subjects with a BMI of 24–30 kg/m2 and serum levels of TG of 100–250 mg/dl at a potentially effective dose of G-hesperidin (500 mg)  with that of caffeine (25, 50, or 75 mg) .