Omega-6 Polyunsaturated Fatty Acids (PUFA)

Linoleic acid (LA) and Gamma-linolenic acid (GLA) are key Omega-6 PUFA (have more than one double bond in their structure) which are converted in the body by metabolism to longer carbon chain Omega-6 fatty acids with additional double bonds (Figures 1 and 2). Gamma-linolenic acid  is by convention designated as 18: 3 (n-6) meaning it has 18 carbon atoms and three cis double bonds located at the 6th (therefore designated as an Omega-6 fatty acid), 9th, and 12th positions from the methyl end of the molecule (Figure 1).

Linoleic acid is found in sunflower and corn oils, whereas evening primrose and borage oils contain both LA and GLA. LA has to be converted in the body into GLA for certain biological functions, and this conversion is a metabolically slow process. The longer chain Omega-6 PUFA derived from GLA, particularly arachidonic acid, are found in the membranes of cells of the vascular, immune and nervous systems, and factors such as genes, diet and disease can reduce LA’s conversion to GLA. This can be due to inefficient conversion by the key enzyme delta-6-desaturase (Figure 2). GLA is rapidly converted in the body to the longer chain omega-6 PUFA dihomo-γ-linolenic acid (DGLA) and then desaturated to arachidonic acid (AA) and even further to longer chain omega-6 PUFA (Figure 2). Depending on the activity of Δ5 desaturase in some cell types (which have low activity of the enzyme) only a small fraction of DGLA is converted to AA, whilst in other cell types there is higher conversion to AA. This conversion to DGLA can subsequently produce anti-inflammatory mediators (certain eicosanoids) as well as regulation of pro-inflammatory cytokines. According to some scientists’ further conversion to arachidonic acid (AA) produces similar effects in chronic inflammatory disease. One way to overcome the metabolic limitations in conversion is to supplement the diet with appropriate oil containing GLA.  

Fig 2. Metabolism of n-6 (Omega-6) Polyunsaturated Fatty Acids

Polyunsaturated Fatty Acids in Multiple Sclerosis and Rheumatoid Arthritis

Multiple Sclerosis

Over a dozen published scientific research papers beginning in the early 1970’s have shown that circulating and cellular lipids in Multiple Sclerosis (MS) patients have a disturbed Omega-6 fatty acid pattern. This disturbed Omega-6 fatty acid metabolism in MS is thought by some scientists to lead to dysregulated immune-inflammatory processes as well as loss of specific fatty acids e.g., arachidonic acid which are required by neurones for brain health. The combined data of three clinical trials in MS with Linoleic Acid alone showed reduced relapse rate and severity, and in mildly affected MS a decrease in long term progression. Furthermore, three pilot clinical trials using lipid treatments in MS, where GLA was an important component, have shown significant reductions in relapse rate and improvement in neurological status i.e., improvement of neurological disability scores. In addition, there is evidence, based on both its known biological functions and from studies in MS patients, that GLA can improve cognitive function. 

Rheumatoid arthritis

In a similar way to the importance of immune-inflammatory processes in Multiple Sclerosis these processes are also important in Rheumatoid arthritis (RA) a chronic immune-inflammatory disease that affects the joints rather than the brain. Lower risk as well as clinical improvement of RA has been linked to both the dietary intake of Omega-6 and Omega-3 fatty acids and their levels in blood. Moreover,  GLA has been extensively studied for its potential to reduce the clinical symptoms of RA. Several clinical trials have demonstrated that GLA can reduce joint pain, swelling, and stiffness in RA patients receiving GLA supplements and were able to show significant overall improvements in disease activity when compared to those RA patients receiving a placebo. Furthermore, the anti-inflammatory effects of GLA are attributed to its ability in RA to inhibit the production of inflammatory cytokines and other inflammatory mediators. 

In summary GLA is an omega-6 fatty acid converted in the body to dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA), which can subsequently produce anti-inflammatory mediators and regulate pro-inflammatory cytokines. Because of these biological effects, GLA can be helpful in managing chronic inflammatory diseases by reducing production of pro-inflammatory cytokines and other mediators. This can reduce inflammation and clinical symptoms in conditions such as rheumatoid arthritis, multiple sclerosis and other conditions.