Review: Evidence-based Clinical Research of Anti-obesity Supplements in Japan (2024)

Table 1.

List of Anti-obesity ingredients with company names, product names and the amount of active ingredients.

Table 2.

Evidence list of active ingredients, references, study designs, numbers of subjects, intervention periods, and results.

Ash*taba (Angelica Keiskei)

Ash*taba is a green and yellow vegetable of the Apiaceae Angelica family and contains a rich balance of vitamin and mineral nutrients. Similar to kale, it is often used as a nutritious food ingredient, but has even higher contents of protein; carotene; potassium; vitamins E, K, and B; pantothenic acid; niacin; and dietary fiber. Zhang et al. (2013) demonstrated that ash*taba contains the two main phytochemicals 4-hydroxyderricin (4HD) and xanthoangelol (XAG) (chemical structures ​11), which have various biological effects that lead to anti-tumor, anti-inflammatory, and anti-diabetic activities. 4HD and XAG inhibited differentiation of 3T3-L1 (3T3 is a cell line derived from mouse and used in biological research on adipose tissue) adipocytes by suppressing the expression of cytidine-cytidine-adenosine-adenosine-thymidine enhancer-binding proteins (C/EBP)-β, C/EBP-α, and peroxisome proliferator-activated receptor (PPAR) γ. These effects lead to activation of AMP-activated protein kinase (AMPK), extracellular Signal-regulated kinase (ERK) 1/2, and c-jun N-terminal kinase (JNK) signaling pathways, indicating potential benefits of ash*taba 4HD and XAG in the prevention of obesity and obesity-related disorders [10]. Ohnogi. et al. (2012) reported that ingestion of ash*taba green juice (6.2 g/day) for 8 wks resulted in significant reduction in visceral fat areas (−25.5 cm², p < 0.01), body weight (−1.4 kg, p < 0.05), BMI (−0.5, p < 0.05), and body fat (−2.1%, p< 0.01) in nine adult subjects with metabolic syndrome [11].

Bofu-tsusho-san (An Oriental Herbal Medicine)

Bofu-tsusho-san (BF), a traditional Japanese herbal medicine “kampo” comprising 18 crude components (Table ​33), has been an effective treatment for obesity, constipation, and hypertension. In a clinical trial, BF reduced body weight and improved glucose tolerance [12]. In addition, several pharmacological studies have reported its ability to counter obesity, fatty liver, and arteriosclerotic diseases [13]. As in traditional Chinese medicine, BF was used to reduce fever after bouts of influenza and promote bowel movements. After administering BF, it was demonstrated that BF activates the brown adipose tissue (BAT) and promote the lipolysis in white adipose tissue (WAT). Furthermore, reports of thermogenic responses to BF components from Ephedrae herba (EH), Glycyrrhizae radix (GR), Forsythiae fructus (FF), and Schizonepetae spica (SS) extracts have been reported. These inhibit cyclic adenosine monophosphate (cAMP) phosphodiesterase as shown with caffeine [12]. Nakayama et al. (2007) also showed that BF extracts activated thermogenesis in BAT and inhibited phosphodiesterase activity, resulting in weight loss [14].

Hioki et al. (2004) conducted the randomized, double-blind, placebo-controlled study of BF. Eighty-one obese Japanese women (BMI 36.5 ± 4.8 kg/m²) with IGT and IR were randomized to receive either placebo (n = 40) or BF (24 mg/day) treatments (n = 41). After 24 wks, the BF group had significantly reduced bodyweight (90.8 ± 17.9 to 80 ± 10.3, p < 0.01) and abdominal visceral fat (197.6 ± 69.7 to 104.4 ± 28.0, p < 0.01), without decreases in resting metabolic rates (1986.2 ± 402.5 to 1821 ± 420.6). Whereas the placebo group showed body weight loss (90.3 ± 12.2 to 83.4 ± 13.4, p < 0.05), with no significant changes in abdominal visceral fat (177.2 ± 73.3 to 140.9 ± 60.4) [12].

Capsinoids

Capsinoids are abundant in non-pungent chili peppers (Capsicum anuum L.; Solanacae or pepper fruit; variety CH-19 Sweet) (chemical structures ​22). Watanabe et al. (2011) researched the effects of capsinoids, increased basal metabolism, fatty acid oxidation and decreased body fat. These effects are mediated by transient receptor potential channels (TRP) and the sympathetic nervous system [15].

BAT is a site for cold- and diet-induced thermogenesis, and therefore may be a target for body fat management. Yoneshiro et al. (2013) conducted a 6wk, placebo-controlled study and reported that cold-induced thermogenesis (CIT) was increased after administration of capsinoids (9 mg/day) (200.0 ± 33.9 vs 81.0 ± 32.5 kcal/d) [16]. Because CIT is proportional to BAT activity, these data suggest capsinoid-induced recruitment of BAT.

Orally administered capsiate activates transient receptor potential cation channel, subfamily V, member 1 (TRPV1) receptors on vagal afferents in the gut with equal potency to capsaicin, and results in increased sympathetic efferent activity and thermogenesis in animals [17].

Snitker et al. (2009) conducted a 12-wk, placebo-controlled, double-blind, randomized study in which 80 subjects (BMI 30.4 ± 2.4) were recruited and randomly assigned to capsinoid (6 mg/day) or placebo treatment groups. Capsinoids were well tolerated and mean ± SD weight changes of 0.9 ± 3.1 and 0.5 ± 2.4 kg were observed in capsinoid and placebo groups, respectively (p = 0.86). Abdominal adiposity was also significantly decreased (p = 0.049) in the capsinoid group [17].

DHA/EPA

EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are essential fatty acids (chemical structures ​33). These essential omega-3 fatty acids are found in cold-water fish and are highly unsaturated, with 5 or 6 double bonds on their carbon chains. These polyunsaturated fats play important roles in human physiology⁵.

Inoue et al. (2013) suggested that the ratio of EPA to arachidonic acid (EPA/AA ratio) may have a major role in obesity. The EPA/AA ratio, but not the DHA/AA ratio, was correlated with visceral fat accumulation among men (n = 134) [18].

Some mechanisms by which EPA and DHA act against obesity have been proposed. Specifically, EPA is a ligand of PPARα and activates the expression of genes that encode key enzymes of fatty acid transport and β-oxidation. EPA also improves glucagon like peptide-1 (GLP-1) levels and enhances GLP-1 secretion from intestinal cells by activating G-protein-coupled receptor 120 (GRP120) [19]. GLP-1 also improves insulin secretion and satiety, and moderates postprandial glucose levels. These actions of GLP-1 effectively facilitate visceral fat reduction.

Hill et al. (2007) recruited 75 overweight volunteers (BMI > 25) and investigated the effects of fish oil intake and regular exercise. Subjects were divided into fish oil (FO), FO and exercise (FOX), sunflower oil (SO, control), or SO and exercise (SOX) groups. Oil treatments comprised 6 g of tuna FO/d (including 1.9 g of n-3 fatty acid) or 6 g of SO/d and the exercise regimens involved walking for 45 min for 3 d/week. After the 12-wks intervention, FO supplementation lowered triacylglycerols, increased high density lipoprotein cholesterol (HDL), and improved endothelium-dependent arterial vasodilation (p < 0.05). Both fish oil and exercise independently reduced body fat compared with baseline measurements (p < 0.05) [20].

Forskohlii (South Asian herb)

Coleus forskohlii (CF) is a native Indian coleus plant of the Lamiaceae family that grows wild in arid and semi-arid regions of India and Thailand (chemical structures ​44). The rhizome part of the perennial CF plant has been traditionally used in Ayurvedic medicine as a remedy for heart disease, and respiratory, gastrointestinal, and central nervous systems disorders [21]. The active ingredients forskolin and diterpene act directly on adenylatecyclase, which activates cAMP and stimulates fat catabolism in human adipose cells [22]. CF regulates thermogenic responses to food, increases basal metabolic rates, and increases utilization of body fat. Theoretically, increased release of fatty acids from adipose tissue may also increase thermogenesis, facilitate body fat loss, and increase lean body mass. Enhanced lipolysis is associated with increased use of fat energy, and enhances fat loss without muscle mass loss [23].

Kamohara et al. (2013) performed an 8-wk open-label study of 15 healthy volunteers, who received 1000 mg of CF extract/d (10% forskolin). Subjects achieved significant decreases in BMI (24.92 ± 0.87 to 23.99 ± 0.86 kg/m², p = 0.0038), body weight (66.33 ± 3.00 to 63.96 ± 3.10 kg, p = 0.0038), fat content (29.64 ± 2.19 to 27.77 ± 2.27 kg, p = 0.0038), lean body mass (44.34 ± 2.98 to 43.93 ± 3.01 kg, p = 0.0044), and basal metabolic rates (1379.1 ± 74.4 to 1363.9 ± 77.5 kcal, p = 0.0254) [21].

Garcinia Cambogia

Hydroxycitric acid is an anti-obesity active ingredient found in rinds from the Indian fruit Garcinia cambogia (GC). GC derived hydroxycitric acid (chemical structure ​structure5)5) decreases the synthesis and secretion of very low density lipoprotein (VLDL) in the liver by inhibiting citrate lyase, which ensures the availability of cytosolic acetyl-CoA after mobilization of citrate from mitochondria. As a precursor of malonyl-CoA, acetyl-CoA is the major de novo substrate for fatty acid biosynthesis. Under conditions of decreased fat secretion from the liver, increased plasma chylomicron levels may compensate by providing lipids derived from dietary sources, potentially under the influence of the hormone leptin [24]. Finally, hydroxycitric acid competitively inhibits the extramitochondrial enzyme adenosine triphosphate-citrate (pro-3S)-lyase, which may inhibit de novo lipogenesis as a citrate cleavage enzyme. Taken together, these mechanisms suggest that GC may lower body weight and reduce fat mass in humans [25].

Various supplements contain GC with other components. However, GC is investigated in only one clinical study. Namely, Hayamizu (2003) et al. performed a double-blind, randomized, placebo-controlled, parallel-group design trial of 44 subjects (GC, n = 18; placebo, n = 21) aged 20–65 years with visceral fat areas of >90 cm². Subjects were randomly assigned to receive GC extract for 12 wks (1667.25 mg/9 tablets, containing 1000 mg of hydroxycitric acid). At 16 wk, the GC group had significantly reduced visceral, subcutaneous and total fat areas compared with placebo group (p < 0.001). However, neither body weight nor BMI were significantly lower in the GC group [26].

Lactoferrin

Lactoferrin (LF) is an iron-binding glycoprotein found in exocrine secretions such as breast milk, tears, sweat, and saliva. It is accepted that LF is a protective factor that prevents attacks from exogenous bacteria and viruses. LF has been shown to influence master regulators of adipocyte differentiation such as PPARγ, and inhibits the expression of genes encoding lipid synthesis enzymes, and hence lipid accumulation in preadipocytes. In recent experiments, LF increased cellular cAMP concentrations and reduced the expression of perilipin, further promoting lipolysis in mature adipocytes. Furthermore, the well-known lactoferrin receptor lipoprotein receptor related protein-1 (LRP1) is expressed in mesenteric fat and mediates accumulation of lactoferrin, suggesting that lactoferrin acts directly on adipocytes as visceral lactoferrin [27-28].

Ono et al. (2010) performed a double-blind, placebo-controlled design study of 22–60-year-old Japanese men and women (n = 26) with abdominal obesity (BMI > 25 kg/m² and visceral fat area > 100 cm²). Subjects consumed enteric-coated LF (eLF) (300 mg/d as bovine LF) or placebo tablets for 8 wks and total visceral and subcutaneous fat areas were measured using computed tomography. In comparison with the placebo group, visceral fat area was significantly reduced in the eLF group (−1.8 vs. −14.6 cm², respectively, p = 0.009; ANCOVA). Decreases in body weight, BMI, and hip circumference in the eLF group (−1.5 kg, −0.6 kg/m², and −2.6 cm, respectively) were also significantly greater than those in placebo group (1.0 kg, 0.3 kg/m², and −0.2 cm; p = 0.032, 0.013, and 0.041, respectively). There was also a tendency for a reduced waist circumference in the eLF group (−4.4 cm) when compared with the placebo group (−0.9 cm; p = 0.073) [28].

L-Carnitine

L-Carnitine (LC) is a vitamin-like amino acid derivative (chemical structure ​structure6)6) involved in metabolism of lipid and use of fat energy. LC promotes transport of long chain fatty acids across the selective inner membrane into the mitochondrial matrix for further β-oxidation. In addition to endogenous supply from liver, kidney, and other organs, LC is also ingested from foods such as lean meat [29].

Wutzke et al. (2004) showed that oral administration of LC to healthy human subjects for 10 days significantly facilitated fatty acid oxidation, indicating that LC may be a limiting factor for fat catabolism. Oyanagi et al. (2011) showed protective effects of LC vs. free fatty acid against mitochondrial membrane disruption, resulting in sustained β-oxidation functionally. These observations suggest that LC supplementation may attenuate obesity by improving rate limiting mitochondrial processes [30-31].

Odo et al. (2013) recruited 24 overweight (BMI 25.8–26.6 kg/m²) male subjects for a double-blind randomized placebo-controlled study. In this trial, low-dosage (500 mg/day) LC supplementation and motivation training for 4 wks resulted in significant body weight loss (82.0 ± 2.2 to 80.9 ± 1.8 kg, p < 0.01) and decreased serum triglyceride levels (218 ± 45 to 145 ± 42, p < 0.01) compared with non-motivated placebo-treated subjects [32].

Oligonol (Lychee polyphenol)

Oligonol is a lychee fruit-derived polyphenol that is oligomerized during manufacture of catechin-type monomers and proanthocyanidin oligomers (chemical structure ​77). Diabetes-induced hepatic damage is occasionally observed in patients with metabolic syndrome. Oligonol has been shown to protect against hepatic damage by regulating oxidative stress and lipid metabolism in vitro and in vivo [33]. Ogasawara et al. (2010) demonstrated a mechanism for oligonol-improved lipid metabolism that involves the mitogen activated-protein kinase (MAPK) signaling pathway. Oligonol stimulated lipolysis in primary adipocytes by activating Ras and phosphorylated (Raf-1) and MEK1/2 independent of autocrine/paracrine interleukin 6 (IL6), leading to significant activation of ERK1/2 proteins and decreased secretion of IL-6 from adipocytes [34].

Nishihira et al. (2009) performed a randomized double-blind, placebo-controlled clinical trial of oligonol in 18 adult volunteers with abdominal circumference of >85 cm. Subjects were enrolled and divided into groups treated with 50 mg oligonol or placebo/d for 10 wks. Clinical parameters such as waist circumference (p < 0.01), subcutaneous fat area (p < 0.05) and visceral fat area (80.5 ± 45.8 to 68.6 ± 36.5 cm², p < 0.05) were significantly decreased in the oligonol group compared with placebo treated subjects [35].

Tea Catechin

Polyphenol bioactivities have recently become topical in medicine and cosmetics. Green tea, which has been consumed in Asian countries for centuries, contains low-molecular-weight polyphenols comprising mainly flavanol (flavan-3-ol) monomers, which are referred to as catechins (chemical structure ​88) [36]. Green tea components have been shown to affect PPAR signaling pathways. Lee et al. (2004) reported that green tea and its main constituent epigallocatechin gallate (EGCG) increased the activation of PPAR [37]. Tea catechins also suppressed adipocyte differentiation and downregulated PPARγ and C/EBPα [38], which is a family of ligand-activated transcription factors of the nuclear receptor superfamily and is critical to fat metabolism and activation of PPARs.

Nagao et al. (2005) investigated the effects of tea catechin in 38 healthy normal to overweight men. Subjects were divided into 2 groups with similar BMI and waist circumference distribution, and ingested 1 bottle of oolong tea/d containing 690 mg of catechins (green tea extract group; n = 17) or 1 bottle of oolong tea/d containing 22 mg of catechins (control group; n = 18). After 12 wks, the green tea extract group achieved significant reduction in body weight (p < 0.01; vs. placebo p < 0.05), BMI (p < 0.01; vs placebo p < 0.05), waist circumference (p < 0.01; vs placebo p < 0.05), body fat mass (p < 0.01; vs placebo p < 0.05), and subcutaneous fat area (p < 0.01; vs placebo p < 0.05). Changes in the concentrations of malondialdehyde-modified LDL were positively associated with changes in body fat mass and total fat area in the green tea extract group [36].

Yeast Hydrolysate

The typical yeast Saccharomyces cerevisiae is used routinely in the production of sake and bread. Yeast hydrolysates (YH) from S. cerevisiae are solubilized using protein degradation enzymes. Jung et al. (2013) indicated that YH may act against obesity by suppressing appetite through appetite-related neurotransmitters in the central nervous system (CNS). YH is rich in cyclo-his-pro (CHP), which plays an important role in the regulation of leptin and has been associated with presynaptic dopaminergic mechanisms and leptin-like functions in CNS. Importantly, CHP reduces body weight by inhibiting food intake [39].

Jung et al. (2013) also conducted the first randomized, double-blind, placebo-controlled study of YH. They showed that YH treatment for 10 wks inhibited abdominal fat accumulation in 54 obese (BMI > 25) men and women aged 20–50 years. From wk 6, energy intake in the YH (1 g/d) treatment group was significantly reduced compared with that in the control group (placebo 1 g/d; P < 0.05). Reduction in body weight and body mass index (BMI) between baseline and wk 10 were also significantly greater in the YH group than in the control group (body weight, -2.60 vs. +0.83 kg, p < 0.001; BMI: -0.90 vs. +0.29 kg/m²; p < 0.001)⁷.

Table 4.

List of anti-obesity materials, company names, and resons for exclusion from table 1.

¹Global strategy on diet, physical activity and health. In The Fifty-seventh World Health Assembly, 2007; pp 38-55.

²Trends in the Market for Dietary Supplement, Health Ingredients and Production Technology. http://www.kenko-media.com/food_devlp/skpdf/1303-sd-01.pdf [Accessed on 3^rd October 2013].

³Chemical structures were drawn based on the Pub Chem Compound database.

⁴Whiting, S.; Derbyshire, E.; Tiwari, B. K., Capsaicinoids and capsinoids. A potential role for weight management? A systematic review of the evidence. Appetite 2012, 59 (2), 341-8.

⁵Dr. Hoffman Home Page. What are EPA/DHA? http://www.drhoffman.com/page.cfm/84 [Accessed on 3^rd October 2013].

⁶Technical Resources International, GarciniaCambogia, http://ntp.niehs.nih.gov/ntp/htdocs/Chem_Background/ExSumPdf/GarciniaCambogiaExt_508.pdf [Accessed 25^th November 2013].

⁷Jung, E. Y.; Cho, M. K.; Hong, Y.-H.; Kim, J. H.; Park, Y.; Chang, U. J.; Suh, H. J., Yeast hydrolysate can reduce body weight and the abdominal fat accumulation in obese adults. Nutrition 2013. in press

⁸Ministry of Health, Labor and Welfare. Food for Specified Health Uses (FOSHU). http://www.mhlw.go.jp/english/topics/foodsafety/fhc/02.html [Accessed 3^rd October 2013].

⁹National Center for Complementary & Alternative Medicine (NCCAM). Dietary and Herbal Supplements. http://nccam.nih.gov/health/supplements[Accessed 1^st October 2013].

4HD

 = 4-hydroxyderricin

AA

 = Arachidonic acid

AMPK

 = AMP-activated protein kinase

BAT

 = Brown adipose tissue

BF

 = Bofu-tsusho-san

BMI

 = Body mass index

C/EBP

 = CCAAT enhancer-binding protein

CAM

 = Complementary and alternative medicines

cAMP

 = Cyclic adenosine monophosphate

CCAAT

 = Cytidine-cytidine-adenosine-adenosine-thymidine

CF

 = Coleus forskohlii

CHP

 = Cyclo-his-pro

CIT

 = Cold-induced thermogenesis

CNS

 = Central nervous system

DHA

 = Docosahexaenoic acid

EGCG

 = Epigallocatechin gallate

EH

 = Ephedrae herba

eLF

 = Enteric-coated LF

EPA

 = Eicosapentaenoic acid

ERK

 = Extracellular Signal-regulated kinase

FF

 = Forsythiae fructus

FO

 = Fish oil

FOSHU

 = Food for specified health use

FOX

 = FO and exercise

GC

 = Galcinia cambogia

GLP-1

 = Glucagon like peptide-1

GLP120

 = G-protein-coupled receptor 120

GR

 = Glycyrrhizae radix

HDL

 = High density lipoprotein

IGT

 = Impaired glucose tolerance

IL-6

 = Interleukin 6

IR

 = Insulin resistance

JNK

 = c-jun N-terminal kinase

LC

 = L-carnitine

LF

 = Lactoferrin

LRP1

 = Lipoprotein receptor related protein-1

MAPK

 = Mitogen activated-protein kinase

NCCAM

 = National center for complementary and alternative medicine

PPAR

 = Peroxisome proliferator-activated receptor

Pro-3S

 = Triphosphate-citrate

Raf-1

 = Ras and phosphorylated

SO

 = Sunflower oil

SOX

 = SO and exercise

SS

 = Schizonepetae spica

TOKUHO

 = Tokutei hokenyou shokuhin (in Japanese)

TRP

 = Transient receptor potential channels

TRPV1

 = Transient receptor potential cation channel, subfamily V, member 1

VLDL

 = Very low-density lipoprotein

WAT

 = White adipose tissue

XAG

 = Xanthoangelol

YH

 = Yeast hydrolysates

1. Park T, Kim Y. Phytochemicals as potential agents for prevention and treatment of obesity and metabolic diseases. Anti-Obes. Drug Discov. Dev. 2011;1:150–185. [Google Scholar]

2. Santos AP, Rogero MM, Bastos DH. Edible plants, their secondary metabolites and antiobesogenic potential. Recent Pat. Food Nutr. Agric. 2010;2(3):195–212. [PubMed] [Google Scholar]

3. Rayalam S, Della-Fera MA, Baile CA. Phytochemicals and regulation of the adipocyte life cycle. J. Nutr. Biochem. 2008; 19(11):717–726. [PubMed] [Google Scholar]

4. Krzyzanowska J, Czubacka A, Oleszek W. Dietary phytochemicals and human health. Adv. Exp. Med. Biol. 2010;698:74–98. [PubMed] [Google Scholar]

5. Visioli F, Borsani L, Galli C. Diet and prevention of coronary heart disease: the potential role of phytochemicals. Cardiovasc. Res. 2000;47(3):419–425. [PubMed] [Google Scholar]

6. Visioli F, Bogani P, Grande S, Detopoulou V, Manios Y, Galli C. Local food and cardioprotection: the role of phytochemicals. Forum Nutr. 2006;59:116–129. [PubMed] [Google Scholar]

7. Gonzalez-Castejon M, Rodriguez-Casado A. Dietary phytochemicals and their potential effects on obesity: a review.Pharmacol. Res. Off. J. Ital. Pharmacol. Soc. 2011;64(5):438–455. [PubMed] [Google Scholar]

8. Dwyer JT, Allison DB, Coates PM. Dietary supplements in weight reduction. J. Am. Diet. Assoc. 2005;105(5) Suppl. 1:S80–86. [PubMed] [Google Scholar]

9. Sumi R, Maeda K, Ito T, editors. In The Guidebook of Japanese Society for Medical Use of Functional Foods. Japan: Ishiyaku Shuppan:; 2012. Metabolic System- Obesity. pp. 37–40. [Google Scholar]

10. Zhang T, Sawada K, Yamamoto N, Ashida H. 4-Hydroxyderricin and xanthoangelol from Ash*taba (Angelica keiskei) suppress differentiation of preadiopocytes to adipocytes via AMPK and MAPK pathways. Mol. Nutr. Food Res. 2013;57(10):1729–1740. [PubMed] [Google Scholar]

11. Ohnogi H, Hayami S, Kudo Y, Enoki T. Efficacy and Safety of Ash*taba (Angelica keiskei) on the Patients and Candidates with Metabolic Syndrome: A Pilot Study. Jpn J. Complement. Alternat. Med. 2012;9(1):49–55. [Google Scholar]

12. Hioki C, Yoshimoto K, Yoshida T. Efficacy of bofu-tsusho-san an oriental herbal medicine in obese Japanese women with impaired glucose tolerance. Clin. Exp. Pharmacol. Physiol. 2004;31(9):614–619. [PubMed] [Google Scholar]

13. Shimada T, Kudo T, Akase T, Aburada M. Preventive effects of Bofutsushosan on obesity and various metabolic disorders. Biol. Pharm. Bull. 2008;31(7):1362–1367. [PubMed] [Google Scholar]

14. Nakayama T, Suzuki S, Kudo H, Sassa S, Nomura M, Sakamoto S. Effects of three Chinese herbal medicines on plasma and liver lipids in mice fed a high-fat diet. J. Ethnopharmacol. 2007;109(2):236–240. [PubMed] [Google Scholar]

15. Watanabe T, Ohnuki K, Kobata K. Studies on the metabolism and toxicology of emerging capsinoids. Expert Opin. Drug Metab. Toxicol. 2011;7(5):533–542. [PubMed] [Google Scholar]

16. Yoneshiro T, Aita S, Matsush*ta M, Kayahara T, Kameya T, Kawai Y, Iwanaga T, Saito M. Recruited brown adipose tissue as an antiobesity agent in humans. J. Clin. Investig. 2013;123(8):3404–3408. [PMC free article] [PubMed] [Google Scholar]

17. Snitker S, Fujishima Y, Shen H, Ott S, Pi-Sunyer X, Furuhata Y, Sato H, Takahashi M. Effects of novel capsinoid treatment on fatness and energy metabolism in humans: possible pharmacogenetic implications. Am. J. Clin. Nutr. 2009;89(1):45–50. [PMC free article] [PubMed] [Google Scholar]

18. Inoue K, Kishida K, Hirata A, Funahashi T, Shimomura I. Low serum eicosapentaenoic acid / arachidonic acid ratio in male subjects with visceral obesity. Nutr. Metab. 2013;10(1):25. [PMC free article] [PubMed] [Google Scholar]

19. Senmaru T, f*ckui M, Kobayashi K, Iwase H, Inada S, Okada H, Asano M, Yamazaki M, Hasegawa G, Nakamura N, Iwasaki M, Yabe D, Kurose T, Seino Y. Dipeptidyl-peptidase IV inhibitor is effective in patients with type 2 diabetes with high serum eicosapentaenoic acid concentrations. J. Diabetes Investig. 2012;3(6):498–502. [PMC free article] [PubMed] [Google Scholar]

20. Hill AM, Buckley JD, Murphy KJ, Howe PR. Combining fish-oil supplements with regular aerobic exercise improves body composition and cardiovascular disease risk factors. Am. J. Clin. Nutr. 2007;85(5):1267–1274. [PubMed] [Google Scholar]

21. Kamohara S, Noparatanawong S. A Coleus forskohlii extract improves body composition in healthy volunteers: An open-label trial. Person. Med. Univ. 2013;2:25–27. [Google Scholar]

22. Astell KJ, Mathai ML, Su XQ. A review on botanical species and chemical compounds with appetite suppressing properties for body weight control. Plant Food Hum. Nutr. 2013;68(3):213–221. [PubMed] [Google Scholar]

23. Henderson S, Magu B, Rasmussen C, Lancaster S, Kerksick C, Smith P, Melton C, Cowan P, Greenwood M, Earnest C, Almada A, Milnor P, Magrans T, Bowden R, Ounpraseuth S, Thomas A, Kreider R B. Effects of coleus forskohlii supplementation on body composition and hematological profiles in mildly overweight women. J. Int. Soc. Sports Nutr. 2005;2:54–62. [PMC free article] [PubMed] [Google Scholar]

24. Oluyemi KA, Omotuyi IO, Jimoh OR, Adesanya OA, Saalu CL, Josiah SJ. Erythropoietic and anti-obesity effects of Garcinia cambogia (bitter kola) in Wistar rats. Biotechnol. Appl. Biochem. 2007;46 (Pt. 1):69–72. [PubMed] [Google Scholar]

25. Heymsfield SB, Allison DB, Vasselli JR, Pietrobelli A, Greenfield D, Nunez C. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. JAMA. 1998;280(18):1596–1600. [PubMed] [Google Scholar]

26. Hayamizu K, Ishii Y, Kaneko I, Shen M, Okuhara Y, Shigematsu N, Tomi H, Furuse M, Yoshino G, Shimasaki H. Effects of garcinia cambogia (hydroxycitric acid) on visceral fat accumulation: a double-blind randomized placebo-controlled trial. Curr. Ther. Res. 2003;64(8):551–567. [PMC free article] [PubMed] [Google Scholar]

27. Ono T, Morish*ta S, Murakoshi M. Novel function of bovine lactoferrin in lipid metabolism: Visceral fat reduction by enteric-coated lactoferrin. Pharma Nutrition. 2013;1(1):32–34. [Google Scholar]

28. Ono T, Murakoshi M, Suzuki N, Iida N, Ohdera M, Iigo M, Yoshida T, Sugiyama K, Nishino H. Potent anti-obesity effect of enteric-coated lactoferrin: decrease in visceral fat accumulation in Japanese men and women with abdominal obesity after 8-week administration of enteric-coated lactoferrin tablets. Br. J. Nutr. 2010;104(11):1688–1695. [PubMed] [Google Scholar]

29. Costell M, O'Connor JE, Grisolía S. Age-dependent decrease of carnitine content in muscle of mice and humans. Biochem. Biophys. Res. Commun. 1989;161(3):1135–1143. [PubMed] [Google Scholar]

30. Oyanagi E, Yano H, Uchida M, Utsumi K, Sasaki J. Protective action of l-carnitine on cardiac mitochondrial function and structure against fatty acid stress. Biochem. Biophys. Res. Commun. 2011;412(1):61–67. [PubMed] [Google Scholar]

31. Wutzke KD, Lorenz H. The effect of l-carnitine on fat oxidation, protein turnover, and body composition in slightly overweight subjects. Metab. Clin. Exp. 2004;53(8):1002–1006. [PubMed] [Google Scholar]

32. Odo S. A pilot clinical trial on l-carnitine supplementation in combination with motivation training: effects on weight management in healthy volunteers. Food Nutr. Sci. 2013;04(2):222–231. [Google Scholar]

33. Noh JS, Park CH, Yokozawa T. Treatment with oligonol, a low-molecular polyphenol derived from lychee fruit, attenuates diabetes-induced hepatic damage through regulation of oxidative stress and lipid metabolism. Br. J. Nutr. 2011;106(7):1013–1022. [PubMed] [Google Scholar]

34. Ogasawara J, Kitadate K, Nishioka H, Fujii H, Sakurai T, Kizaki T, Izawa T, Ishida H, Tanno M, Ohno H. Oligonol an oligomerized lychee fruit-derived polyphenol, activates the Ras/Raf-1/MEK1/2 cascade independent of the IL-6 signaling pathway in rat primary adipocytes. Biochem. Biophys. Res. Commun. 2010;402(3):554–559. [PubMed] [Google Scholar]

35. Nishihira J, Sato-Ueshima M, Kitadate K, Wakame K, Fujii H. Amelioration of abdominal obesity by low-molecular-weight polyphenol (Oligonol) from lychee. J. Funct. Foods. 2009;1(4):341–348. [Google Scholar]

36. Nagao T, Komine Y, Soga S, Meguro S, Hase T, Tanaka Y, Tokimitsu I. Ingestion of a tea rich in catechins leads to a reduction in body fat and malondialdehyde-modified LDL in men. Am. J. Clin. Nutr. 2005;81(1):122–129. [PubMed] [Google Scholar]

37. Lee K. Transactivation of peroxisome proliferator-activated receptor alpha by green tea extracts. J. Vet. Sci. 2004;5(4):325–330. [PubMed] [Google Scholar]

38. Abe K, Okada N, Tanabe H, f*ckutomi R, Yasui K, Isemura M, Kinae N. Effects of chronic ingestion of catechin-rich green tea on hepatic gene expression of gluconeogenic enzymes in rats. Biomed. Res. 2009;30(1):25–29. [PubMed] [Google Scholar]

39. Jung EY, Hong YH, Kim JH, Park Y, Bae SH, Chang UJ, Suh HJ. Effects of yeast hydrolysate on hepatic lipid metabolism in high-fat-diet-induced obese mice: yeast hydrolysate suppresses body fat accumulation by attenuating fatty acid synthesis. Ann. Nutr. Metab. 2012;61(2):89–94. [PubMed] [Google Scholar]