A Novel Emulsion Gel Formulation Improves the Bioavailability of DHA in Healthy Adults: A Randomized Controlled Clinical Study

Xiaomin Huang¹, Shaofeng Huo², Xuan Sun³, Qiuyu Xu¹, Weiguo Zhang⁴, Suqiong Fang¹, Bingqi Xie¹, Yirui Zheng¹ and Peng Chen^1,

¹R&D, Sirio Pharma Co., Ltd, Shantou, Guangdong, China

²R&D, Sirio Life Technology (Shanghai) Co., Ltd, Shanghai, China

³R&D, Sirio Healthcare (Anhui) Co., Ltd, Maanshan, Anhui, China

⁴Las Colinas Institutes, Irving, TX, United States

Cite this paper:
Xiaomin Huang, Shaofeng Huo, Xuan Sun, Qiuyu Xu, Weiguo Zhang, Suqiong Fang, Bingqi Xie, Yirui Zheng and Peng Chen. A Novel Emulsion Gel Formulation Improves the Bioavailability of DHA in Healthy Adults: A Randomized Controlled Clinical Study. Journal of Food and Nutrition Research. 2024; 12(11):508-512. doi: 10.12691/jfnr-12-11-6

Abstract

Docosahexaenoic acid (DHA) is an omega-3 long-chain polyunsaturated fatty acid (LCPUFA), playing roles structurally and functionally from growth to health and the pathogenesis of diseases. Being a common nutrient supplement, the bioavailability of DHA is practically important. This study assessed the bioavailability of DHA after oral administration of emulsified DHA Gel Tablet, which was developed and manufactured by SIRIO and non-emulsified DHA algal oil in healthy individuals. The protocol was designed as a randomized, open, parallel clinical study. 19 healthy adults between 23 and 40 years old were randomly assigned into two groups receiving equal doses (300 mg) but different forms of DHA (DHA Gel Tablet, n = 10; DHA algal oil, n=9) in a fasting state. The blood was sampled at 0, 1, 2, 2.5, 3, 3.5, 4, 5, and 6 hours after ingestion. Free DHA in plasma was measured by liquid chromatography with LC-MS/MS. The maximum plasma concentration (C_max), the time to maximum concentration (T_max), and the area under the curve (AUC_0-6) were calculated from the measurements of free DHA. Compared with the DHA algal oil, the DHA Gel Tablet exhibited a higher C_max (0.772 ± 0.556 vs 0.308 ± 0.186 μg/ml, P= 0.0293) and greater AUC_0-6 (1.611 ± 1.366 vs 0.550 ± 0.311 μg/ml*h, P =0.0491). The pharmacokinetic results showed that the C_max and AUC of the DHA Gel Tablet were 2.506 times higher and 2.929 times larger, indicating higher bioavailability of DHA treated with the emulsion technology. No side effects were observed in either group.

Keywords:
algal lipids docosahexaenoic acid lipid absorption nutrition n-3 fatty acid physiology

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Figures

References:

[1]	F. Zapata-Gonzalez et al., "Human dendritic cell activities are modulated by the omega-3 fatty acid, docosahexaenoic acid, mainly through PPARγ: RXR heterodimers: comparison with other polyunsaturated fatty acids," Journal of Leucocyte Biology, vol. 84, no. 4, pp. 1172-1182, 2008.
[2]	G. Y. Sun et al., "Docosahexaenoic acid (DHA): An essential nutrient and a nutraceutical for brain health and diseases," Prostaglandins, Leukotrienes and Essential Fatty Acids, vol. 136, pp. 3-13, 2018.
[3]	G. C. Burdge and P. C. Calder, "Conversion of $\alpha $-linolenic acid to longer-chain polyunsaturated fatty acids in human adults," Reproduction Nutrition Development, vol. 45, no. 5, pp. 581-597, 2005.
[4]	G. C. Burdge, A. E. Jones, and S. A. Wootton, "Eicosapentaenoic and docosapentaenoic acids are the principal products of α-linolenic acid metabolism in young men," British Journal of Nutrition, vol. 88, no. 4, pp. 355-363, 2002.
[5]	A. H. Mariamenatu and E. M. Abdu, "Overconsumption of omega-6 polyunsaturated fatty acids (PUFAs) versus deficiency of omega-3 PUFAs in modern-day diets: the disturbing factor for their “balanced antagonistic metabolic functions” in the human body," Journal of lipids, vol. 2021, pp. 1-15, 2021.
[6]	I. S. f. t. S. o. F. A. a. L. ISSFAL. Global Recommendations for EPA and DHA Intake (Rev 19 November 2014) [Online] Available: https://www.issfal.org/.
[7]	C. N. S. CNS, in Chinese DRIs Handbook. Chinese Nutrition Society CNS: Chinese Nutrition Society CNS, 2013.
[8]	S. Forsyth, S. Gautier, and N. Salem Jr, "Dietary intakes of arachidonic acid and docosahexaenoic acid in early life-with a special focus on complementary feeding in developing countries," Annals of Nutrition and Metabolism, vol. 70, no. 3, pp. 217-227, 2017.
[9]	Y.-B. Zhou et al., "A correlation study of DHA intake estimated by a FFQ and concentrations in plasma and erythrocytes in mid-and late pregnancy," Nutrients, vol. 9, no. 11, p. 1256, 2017.
[10]	W. Lv and D. Xu, "Docosahexaenoic acid delivery systems, bioavailability, functionality, and applications: A review," Foods, vol. 11, no. 17, p. 2685, 2022.
[11]	I. J. Haug, L. B. Sagmo, D. Zeiss, I. C. Olsen, K. I. Draget, and T. Seternes, "Bioavailability of EPA and DHA delivered by gelled emulsions and soft gel capsules," European journal of lipid science and technology, vol. 113, no. 2, pp. 137-145, 2011.
[12]	Z. He, W. Zeng, X. Zhu, H. Zhao, Y. Lu, and Z. Lu, "Influence of surfactin on physical and oxidative stability of microemulsions with docosahexaenoic acid," Colloids and surfaces B: Biointerfaces, vol. 151, pp. 232-239, 2017.
[13]	C.-C. Yang, C.-F. Hung, and B.-H. Chen, "Preparation of coffee oil-algae oil-based nanoemulsions and the study of their inhibition effect on UVA-induced skin damage in mice and melanoma cell growth," International Journal of Nanomedicine, pp. 6559-6580, 2017.
[14]	E. Jiménez-Martín, A. Gharsallaoui, T. Pérez-Palacios, J. R. Carrascal, and T. A. Rojas, "Suitability of using monolayered and multilayered emulsions for microencapsulation of ω-3 fatty acids by spray drying: effect of storage at different temperatures," Food and bioprocess technology, vol. 8, pp. 100-111, 2015.
[15]	M. Ding, T. Zhang, H. Zhang, N. Tao, X. Wang, and J. Zhong, "Effect of preparation factors and storage temperature on fish oil-loaded crosslinked gelatin nanoparticle pickering emulsions in liquid forms," Food Hydrocolloids, vol. 95, pp. 326-335, 2019.
[16]	E. Liu, S. Zhao, X. Li, X. Meng, and B. Liu, "Preparation, characterization of PLGA/chitosan nanoparticles as a delivery system for controlled release of DHA," International Journal of Biological Macromolecules, vol. 185, pp. 782-791, 2021.
[17]	Q. Xiao, G. Chen, Y. Zhang, H. Weng, M. Cai, and A. Xiao, "Evaluation of a novel self-emulsifiable dodecenyl succinylated agarose in microencapsulation of docosahexaenoic acid (DHA) through spray-chilling process," International Journal of Biological Macromolecules, vol. 163, pp. 2314-2324, 2020.
[18]	C. Qiong et al., "Digestive properties and bioaccessibility of two different algal oil dosage forms based on gastrointestinal dynamic digestion system," Modern Food Science & Technology, vol. 37, no. 8, 2021.
[19]	C. T. Chen et al., "Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain," Scientific reports, vol. 5, no. 1, p. 15791, 2015.
[20]	M. Armand et al., "Characterization of emulsions and lipolysis of dietary lipids in the human stomach," American Journal of Physiology-Gastrointestinal and Liver Physiology, vol. 266, no. 3, pp. G372-G381, 1994.
[21]	M. Armand et al., "Physicochemical characteristics of emulsions during fat digestion in human stomach and duodenum," American Journal of Physiology-Gastrointestinal and Liver Physiology, vol. 271, no. 1, pp. G172-G183, 1996.
[22]	I. Garaiova, I. A. Guschina, S. F. Plummer, J. Tang, D. Wang, and N. T. Plummer, "A randomised cross-over trial in healthy adults indicating improved absorption of omega-3 fatty acids by pre-emulsification," Nutrition Journal, vol. 6, pp. 1-9, 2007.
[23]	I. Ikeda, "Digestion and absorption of structured lipids," 2000.
[24]	P. Borel et al., "Digestion and absorption of tube‐feeding emulsions with different droplet sizes and compositions in the rat," Journal of parenteral and enteral nutrition, vol. 18, no. 6, pp. 534-543, 1994.
[25]	M. Armand et al., "Digestion and absorption of 2 fat emulsions with different droplet sizes in the human digestive tract," The American journal of clinical nutrition, vol. 70, no. 6, pp. 1096-1106, 1999.
[26]	S. K. Raatz, J. B. Redmon, N. Wimmergren, J. V. Donadio, and D. M. Bibus, "Enhanced absorption of n-3 fatty acids from emulsified compared with encapsulated fish oil," Journal of the American Dietetic Association, vol. 109, no. 6, pp. 1076-1081, 2009.
[27]	A. Acevedo-Fani and H. Singh, "Biophysical insights into modulating lipid digestion in food emulsions," Progress in lipid research, vol. 85, p. 101129, 2022.