Trans Lipid Library: Synthesis of Docosahexaenoic Acid (DHA) Monotrans Isomers and Regioisomer Identification in DHA-Containing Supplements

Abstract

Docosahexaenoic acid (DHA) is a semiessential polyunsaturated fatty acid (PUFA) for eukaryotic cells that is found in natural sources such as fish and algal oils and widely used as an ingredient for omega-3 containing foods or supplements. DHA effects are connected to its natural structure with six cis double bonds, but geometrical monotrans isomers can be formed during distillation or deodorization processes, as an unwanted event that alters molecular characteristics and annihilates health benefits. The characterization of the six monotrans DHA regioisomers is an open issue to address for analytical, biological, and nutraceutical applications. Here we report the preparation, separation, and first identification of each isomer by a dual approach consisting of the following: (i) the direct thiyl radical-catalyzed isomerization of cis-DHA methyl ester and (ii) the two-step synthesis from cis-DHA methyl ester via monoepoxides as intermediates, which are separated and identified by nuclear magnetic resonance spectroscopy, followed by elimination for the unequivocal assignment of the double bond position. This monotrans DHA isomer library with NMR and GC analytical characterization was also used to examine the products of thiyl-radical-catalyzed isomerization of a fish oil sample and to evaluate the trans isomer content in omega-3 containing supplements commercially available in Italy and Spain.

Biomimetic Ketone Reduction by Disulfide Radical Anion

“…The comprehension of free radical reactivity taking place in naturally occurring processes can be very important for chemistry in two main ways: (1) inspiring new synthetic methods based on the same mechanisms that nature uses to prepare biomolecules, and (2) designing biomimetic models to simulate the free radical damages and to provide molecular libraries for mechanistic and biomarker discovery. Two successful examples of these approaches from our group are the syntheses of 5 ,8-cyclopurine lesions [1][2][3] and mono-trans PUFA isomers [4][5][6]. Indeed, there are strict relationships between reactivity involving free radicals and processes taking place in nature [7].…”

A Journey through ω-3 Supplements: Future Perspectives for Precision Nutrition

“…At the same time, levels of trans-isomers have been measured in different concentrations [36] likely due to the high temperatures and pressures used during the manufacturing of concentrated supplements [37]. The dietary intake of trans-fatty acids (TFA) has adverse effects on blood lipid levels, because they cause an increase on LDL-cholesterol and a decrease on HDL-cholesterol [38], both well-established markers of cardiovascular disease [39].…”

Free-Radical-Mediated Formation of Trans-Cardiolipin Isomers, Analytical Approaches for Lipidomics and Consequences of the Structural Organization of Membranes

“…In lipid chemistry, the free-radical-mediated cis-trans isomerization process contributes, together with hydrogenation and lipid peroxidation processes, to cause alteration of the naturally occurring unsaturated fatty-acid-containing lipids [ 1 , 2 , 3 ]. These processes have a trans-disciplinary relevance, being identified in biological pathways of radical stress as well as in industrial food and nutraceutical production [ 3 , 4 , 5 , 6 ]. Analytical protocols have been established to determine trans lipid presence in living organisms as well as in nutraceutical formulations, which can affect health [ 4 , 5 , 6 ].…”

“…These processes have a trans-disciplinary relevance, being identified in biological pathways of radical stress as well as in industrial food and nutraceutical production [ 3 , 4 , 5 , 6 ]. Analytical protocols have been established to determine trans lipid presence in living organisms as well as in nutraceutical formulations, which can affect health [ 4 , 5 , 6 ].…”