Docosahexaenoic acid Other names: Doconexent

A regular intake of the concentrate in diet leads to a sustained reduction in plasma triglyceride levels following which the values remain on a plateau with continued use or return within two or three months to previous levels if the concentrate is discontinued. The polyunsaturated fatty acids are incorporated into the normal lipid metabolism but are not identifiable to any extent in depot fat. The mechanism of effect appears to be via inhibition of triglyceride synthesis.

Docosahexaenoic acid is a poor substrate for the enzymes responsible for triglyceride synthesis and it inhibits esterification of other fatty acids. So, it reduces the synthesis of triglycerides in the liver.

During and after absorption, there are three main pathways for the metabolism of the omega-3 fatty acids:

• the fatty acids are first transported to the liver where they are incorporated into various categories of lipoproteins and then channelled to the peripheral lipid stores;
• the cell membrane phospholipids are replaced by lipoprotein phospholipids and the fatty acids can then act as precursors for various eicosanoids;
• the majority is oxidised to meet energy requirements.

Animal pharmacokinetic studies have shown that there is a complete hydrolysis of the ethyl ester accompanied by satisfactory absorption and incorporation of DHA into the plasma phospholipids and cholesterol esters.

The absorption of DHA is similar to that of other dietary lipids, i.e. mainly from the upper part of the small intestine and it is distributed into plasma fatty acids and blood cell lipids. The concentration of DHA in the plasma phospholipids corresponds DHA incorporated into the cell membranes. The total plasma glyceride levels of DHA increase from a pre-treatment level of 0.5% to a peak of 15% at 12 days, falling then to plateau levels of 18% after 16 days.

There is a corresponding decrease in the level of ω6 fatty acids in free and bound form as plasma triglycerides. DHA is widely distributed following absorption from the gut and the effect has been quantified in weanling and adult rats. DHA accumulated in all tissues except adipose tissue and to a lesser extent in platelets. DHA has a high affinity for retina, brain and heart lipids.

Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction. In addition non-clinical literature data on safety pharmacology are indicating that there is no hazard for humans.