The disclosure provides methods of synthesizing very long chain fatty acids, including deuterated very long chain fatty acids. The fatty acids can by polyunsaturated fatty acids. The methods include the step of reacting a protected leaving group (L)-substituted saturated aliphatic group with a halo-substituted unsaturated aliphatic group to form a protected aliphatic group. The protected aliphatic group is deprotected to form an alcohol. The alcohol is then oxidized, thereby forming a very long chain fatty acid.