Changes in Bioavailability of Omega-3 (DHA) through Alpha-Tocopheryl Phosphate Mixture (TPM) after Oral Administration in Rats

Abstract

Benefits of Omega-3 Docosahexaenoic acid (DHA) supplements are hindered by their poor solubility and bioavailability. This study investigated the bioavailability of various formulations of Omega-3 and tocopheryl phosphate mixture (TPM), following oral administration in rats, and assessed whether TPM could improve the oral absorption of DHA. The rats were administered with a high (265.7 mg/kg) or low dose (88.6 mg/kg) of DHA. TPM was examined at 1:0.1 w/w (low TPM dose) and 1:0.5 w/w (high TPM dose). Over 24 h, the DHA plasma concentration followed a TPM dose-dependent relationship, reflected in the higher mean Cmax values (78.39 and 91.95 μg/mL) and AUC values (1396.60 and 1560.60) for the low and high TPM, respectively. The biggest difference between the low dose DHA control (LDCont) and TPM formulations was at 4 h after supplementation, where the low and high TPM showed a mean 20% (ns) and 50% (p < 0.05) increase in DHA plasma concentrations versus the control formulation. After correcting for baseline endogenous DHA, the mean plasma DHA at 4 h produced by the LD-HTPM was nearly double (90%) the LDC control (p = 0.057). This study demonstrated that co-administering omega-3 with TPM significantly increases the bioavailability of DHA in the plasma, suggesting potential use for commercially available TPM + DHA fortified products.

Essential Fatty Acids as Biomedicines in Cardiac Health

“…On the negative side, the acquisition of beneficial properties from omega 3 fatty acids is restricted due to poor water solubility and weak oral bioavailability. For example, fish oils are prone to lipid oxidative processes due to their high level of unsaturation, which can affect their regular consumption by promoting a fishy and rancid odor, and even promote adverse effects for health [126][127][128]. Notably, in fish oils, DHA and EPA are naturally bound by default in triacylglycerides, while a wide variety of fish oil capsules are composed of fatty acids bound in ethyl-esters and re-esterified triacylglycerides.…”

“…Previous studies suggested that lipid-based formulations can improve the bioavailability of ω-3, as well as their ingestion with high-fat meals, which can improve their bioavailability [128]. It was also recommended that the ingestion of emulsified forms of omega-3 oils should have higher bioavailability patterns because such supplements can be enriched with absorption enhancers that advance the permeability for the epithelium cells [131].…”

“…In a separate study, a new formulation based on in vivo investigations demonstrated a significant increase in the bioavailability of DHA in the plasma. In this research, ω-3 tocopheryl phosphate mixture (TPM) was prepared from DHA and EPA (DHA 500 and EPA 50 mg/g) combined with tocopheryl phosphate dissolved in foodgrade canola oil (OA 61%, LA 21%, and ALA 11%), which contributed to doubling DHA levels in plasma after 4 h, compared with the control treatment with omega-3 oil (DHA 500TG) without the addition of tocopheryl phosphate mixture [128]. The before-mentioned availability of alpha-tocopheryl phosphate (TPM) as a new lipid excipient for oral delivery for poorly aqueous soluble agents was also correlated with a superior bioavailability in earlier studies, due to compelling safety characteristics, demonstrated to provide cardiopro-tective effects and mitigate atherosclerosis and inflammation [128,140,141].…”

“…In this research, ω-3 tocopheryl phosphate mixture (TPM) was prepared from DHA and EPA (DHA 500 and EPA 50 mg/g) combined with tocopheryl phosphate dissolved in foodgrade canola oil (OA 61%, LA 21%, and ALA 11%), which contributed to doubling DHA levels in plasma after 4 h, compared with the control treatment with omega-3 oil (DHA 500TG) without the addition of tocopheryl phosphate mixture [128]. The before-mentioned availability of alpha-tocopheryl phosphate (TPM) as a new lipid excipient for oral delivery for poorly aqueous soluble agents was also correlated with a superior bioavailability in earlier studies, due to compelling safety characteristics, demonstrated to provide cardiopro-tective effects and mitigate atherosclerosis and inflammation [128,140,141]. Conclusively, the encapsulation and formation of microcapsules will improve the bioavailability of FAs by creating bioactive compounds which can be easily incorporated in food matrixes, to ensure a protected delivery via the digestive system.…”

Vitamin E: Regulatory Role on Signal Transduction

“…At the intestinal epithelium, competition between the hydrophobic vitamins A, D, E, and K for selective uptake involving CD36 and SR-BI also modulates the efficiency of vitamin E uptake (38,39). Vitamin E can also influence the uptake of other lipids from the diet, as demonstrated with a mixture of αTP and di-tocopheryl phosphate able to increase the plasma levels of DHA by twofold (69).…”