Diacylglycerol Oil

Scientific Name(s): Diacylglycerol oil

Common Name(s): Enova , Healthy Econa , DAG oil

Uses

Clinical trials have focused on the use of diacylglycerol (DAG) oil as adjunctive therapy for weight loss and body fat reduction, especially in metabolic syndrome. However, information from clinical trials is limited.

Dosing

DAG oil has been used in clinical trials as replacement for usual consumption of cooking oil, as well as at a variety of fixed daily dosages.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Clinical trials have reported few or no adverse effects.

Toxicology

Chronic rat toxicity studies have revealed no treatment-related effects of DAG oil consumption at levels of up to 5.5% of the diet. No evidence of gene mutation or genotoxic potential has been demonstrated in Ames mutation tests.

History

DAG oil was developed in Japan and launched in February 1999 by Kao Corporation as Healthy Econa cooking oil and is now widely used for cooking and salad oil in Japan. Kao Corporation has since introduced DAG in other products, such as mayonnaise, margarine, and canned tuna. 1 , 2

In 2000, the Food and Drug Administration (FDA) granted Kao and its partner, Archer Daniels Midland Company, “generally recognized as safe” (GRAS) status for their DAG oil product. In the United States, DAG oil is commercially available as Enova oil and may be used in home cooking and vegetable oil spreads. 3

Chemistry

DAG oil is made from the esterification of fatty acids originating from natural edible plant oils, such as soybean and rapeseed oils. 1 , 3 , 4 DAG oil contains only 2 fatty acids and, therefore, has metabolic characteristics distinct from those of conventional triacylglycerol (TAG) oils containing 3 fatty acids. 5 DAG oil is more hydrophilic and water soluble when synthesized enzymatically with the reverse reaction of 1,3-specific lipase. 1 , 5 , 6 Standardized DAG oil contains 1,2-DAG and 1,3-DAG in a 3:7 ratio. 3

The proposed mechanism of action involves the main digestive product of DAG oil, 1- (or 3-)monoacylglycerol, which is poorly re-esterified into TAG in the small intestinal mucosa. 1

Uses and Pharmacology

The majority of published clinical trials have been conducted by the Kao Corporation, primarily among Japanese populations. The design of some of the trials also limits the strength of the findings. Issues present in some of the trials were that they were open-label and single-blind, small sample size with post-hoc subgroup analysis, and inadequate randomization as evidenced by differences in the study groups at onset of the study.

Few quality, independent clinical trials conducted in American populations are available in the literature. 7

Metabolic Syndrome

The majority of studies report the effect of DAG oil consumption on reducing increases in postprandial triglyceride serum levels, especially among insulin-resistant and high body mass index populations. 1 , 8 , 9 , 10 , 11 , 12 Positive changes in certain lipid components, such as remnant-like lipoprotein particle triglycerides, remnant-like lipoprotein particle cholesterol, and chylomicron triglyceride, are reported. 11 , 12 Limited data exist showing a positive effect on glucose metabolism, 1 , 10 , 13 while some trials have shown decreases in body weight with long-term consumption. 8 , 9 , 13 , 14 , 15

However, no difference was found for lipid profiles or glucose and insulin metabolism in some of the trials after 12 weeks and after 1 year of consumption of DAG oil versus TAG oil. 2 , 13 , 14 , 16 In a small (n = 25) crossover study among insulin-resistant participants in the United States, 5 weeks of a DAG oil–enriched diet had no effect on postprandial plasma triglycerides versus TAG oil, and fasting and postprandial glucose and insulin levels were unaffected. 7

Dosage

DAG oil has been used in clinical trials as replacement for usual consumption of cooking oil, as well as at a variety of fixed daily dosages ranging from 10 g per 60 kg body weight to 0.5 g/kg body weight. 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Experiments in rats have shown no adverse fetal/embryonic effects. 21 , 22

Interactions

None well documented. DAG oil reportedly does not affect the absorption of the fat-soluble vitamins A, D, E, or K. 5

Adverse Reactions

Clinical trials report no adverse effects. 19 , 23

Toxicology

1,2-DAG has the potential to activate protein kinase C, an enzyme reportedly involved in tumor promotion activity, and topical application of DAG oil in mice has been reported to increase the incidence of skin carcinomas, leading to concerns regarding the safety of the oil. 3 , 23 However, experiments in rats have failed to demonstrate increased oral cancers, and no difference in protein kinase C activity for DAG oil compared with TAG oil was demonstrated. 3 , 23 It is likely that rapid metabolism of DAG, which reaches the interior of the cell quickly, reverses any protein kinase C activation. Tumor-promoting phorbol esters, on the other hand, are not rapidly metabolized and, therefore, cause persistent protein kinase C activation.

Chronic rat toxicity studies have revealed no treatment-related effects of DAG oil consumption at levels of up to 5.5% of the diet 24 , 25 , 26 (although an anomaly in the findings was noted in one experiment at a lower dosage 25 ). The safety profile of heated DAG oil was found to be the same as that for unheated DAG oil in an experiment in rats. 27 No evidence of gene mutation or genotoxic potential was demonstrated in Salmonella typhimurium or Escherichia coli Ames mutation tests. 3

Bibliography

1. Yanai H, Tomono Y, Ito K, Furutani N, Yoshida H, Tada N. Diacylglycerol oil for the metabolic syndrome. Nutr J . 2007;6:43.
2. Hunter BT. Recent findings about oils. Consum Res Mag . 2002;85:8-9.
3. Amended final report on the safety assessment of glyceryl dilaurate, glyceryl diarachidate, glyceryl dibehenate, glyceryl dierucate, glyceryl dihydroxystearate, glyceryl diisopalmitate, glyceryl diisostearate, glyceryl dilinoleate, glyceryl dimyristate, glyceryl dioleate, glyceryl diricinoleate, glyceryl dipalmitate, glyceryl dipalmitoleate, glyceryl distearate, glyceryl palmitate lactate, glyceryl stearate citrate, glyceryl stearate lactate, and glyceryl stearate succinate. Int J Toxicol . 2007;26(suppl 3):1-30.
4. Umemura T, Maeda M, Kijima A, et al. Lack of promotion activity of diacylglycerol oil on 4-nitroquinoline 1-oxide induced carcinogenesis in the oral cavity of SD rats. Food Chem Toxicol . 2008;46(9):3206-3212.
5. Tada N, Yoshida H. Diacylglycerol on lipid metabolism. Curr Opin Lipido . 2003;14(1):29-33.
6. Matsuo N. Diacylglycerol oil: an edible oil with less accumulation of body fat. Lipid Tech . 2001;13(5):129-133.
7. Reyes G, Yasunaga K, Rothenstein E, et al. Effects of a 1,3-diacylglycerol oil-enriched diet on postprandial lipemia in people with insulin resistance. J Lipid Res . 2008;49(3):670-678.
8. Yamamoto K, Takeshita M, Tokimitsu I, et al. Diacylglycerol oil ingestion in type 2 diabetic patients with hypertriglyceridemia [published correction in Nutrition . 2006;22(3):343]. Nutrition . 2006;22(1):23-29.
9. Ai M, Tanaka A, Shoji K, et al. Suppressive effects of diacylglycerol oil on postprandial hyperlipidemia in insulin resistance and glucose intolerance. Atherosclerosis . 2007;195(2):398-403.
10. Takase H, Shoji K, Hase T, Tokimitsu I. Effect of diacylglycerol on postprandial lipid metabolism in non-diabetic subjects with and without insulin resistance. Atherosclerosis . 2005;180(1):197-204.
11. Taguchi H, Watanabe H, Onizawa K, et al. Double-blind controlled study on the effects of dietary diacylglycerol on postprandial serum and chylomicron triacylglycerol responses in healthy humans. J Am Coll Nutr . 2000;19(6):789-796.
12. Yamamoto K, Asakawa H, Tokunaga K, et al. Long-term ingestion of dietary diacylglycerol lowers serum triacylglycerol in type II diabetic patients with hypertriglyceridemia. J Nutr . 2001;131(12):3204-3207.
13. Li D, Xu T, Takase H, et al. Diacylglycerol-induced improvement of whole-body insulin sensitivity in type 2 diabetes mellitus: a long-term randomized, double-blind controlled study. Clin Nutr . 2008;27(2):203-211.
14. Kawashima H, Takase H, Yasunaga K, et al. One-year ad libitum consumption of diacylglycerol oil as part of a regular diet results in modest weight loss in comparison with consumption of a triacylglycerol control oil in overweight Japanese subjects. J Am Diet Assoc . 2008;108(1):57-66.
15. Yamamoto K, Tomonobu K, Asakawa H, et al. Diet therapy with diacylglycerol oil delays the progression of renal failure in type 2 diabetic patients with nephropathy. Diabetes Care . 2006;29(2):417-419.
16. Takeshita M, Katsuragi Y, Kusuhara M, et al. Phytosterols dissolved in diacylglycerol oil reinforce the cholesterol-lowering effect of low-dose pravastatin treatment. Nutr Metab Cardiovasc Dis . 2008;18(7):483-491.
17. Nagao T, Watanabe H, Goto N, et al. Dietary diacylglycerol suppresses accumulation of body fat compared to triacylglycerol in men in a double-blind controlled trial. J Nutr . 2000;130(4):792-797.
18. Maki KC, Davidson MH, Tsushima R, et al. Consumption of diacylglycerol oil as part of a reduced-energy diet enhances loss of body weight and fat in comparison with consumption of a triacylglycerol control oil. Am J Clin Nutr . 2002;76(6):1230-1236.
19. Yasunaga K, Glinsmann WH, Seo Y, et al. Safety aspects regarding the consumption of high-dose dietary diacylglycerol oil in men and women in a double-blind controlled trial in comparison with consumption of a triacylglycerol control oil. Food Chem Toxicol . 2004;42(9):1419-1429.
20. Hibi M, Takase H, Yasunaga K, et al. Fat utilization in healthy subjects consuming diacylglycerol oil diet: dietary and whole body fat oxidation. Lipids . 2008;43(6):517-524.
21. Morita O, Knapp JF, Tamaki Y, Nemec MD, Varsho BJ, Stump DG. Safety assessment of dietary diacylglycerol oil: a two-generation reproductive toxicity study in rats. Food Chem Toxicol . 2008;46(9):3059-3068.
22. Morita O, Knapp JF, Tamaki Y, Varsho BJ, Stump DG, Nemec MD. Effects of dietary diacylglycerol oil on embryo/fetal development in rats. Food Chem Toxicol . 2008;46(7):2510-2516.
23. Meguro S, Osaki N, Onizawa K, et al. Comparison of dietary triacylglycerol oil and diacylglycerol oil in protein kinase C activation. Food Chem Toxicol . 2007;45(7):1165-1172.
24. Soni MG, Kimura H, Burdock GA. Chronic study of diacylglycerol oil in rats. Food Chem Toxicol . 2001;39(4):317-329.
25. Ichihara T, Yoshino H, Doi Y, et al. No enhancing effects of diacylglycerol oil on tumor development in a medium-term multi-organ carcinogenesis bioassay using male F344 rats. Food Chem Toxicol . 2008;46(1):157-167.
26. Chengelis CP, Kirkpatrick JB, Bruner RH, et al. A 24-month dietary carcinogenicity study of DAG (diacylglycerol) in rats. Food Chem Toxicol . 2006;44(1):98-121.
27. Morita O, Tamaki Y, Kirkpatrick JB, Chengelis CP. Safety assessment of heated diacylglycerol oil: subchronic toxicity study in rats. Food Chem Toxicol . 2008;46(8):2748-2757.

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