Title: Diabetes and n-6 Esential Fatty Acids EFAs

Key words: diabetic neuropathy, omega-6 fatty acids, linoleic acid, prostaglandins, gamma linolenic acid, supplementation

Date: Dec 1999

Category: 13. Specific Conditions

Type: Article

Author: Dr van Rhijn



Diabetes and n-6 Essential Fatty Acids EFAs

The Possible Benefits Of Supplementation in Neuropathy



Polyneuropathy is a common complication of diabetes secondary to direct or indirect (via microcirculation) damage to the nerves. Although the exact mechanism remains unclear, microangiopathy and endoneurial hypoxia are important factors in the pathogenesis. Abnormalities in n-6 essential fatty acid (EFA) metabolism make an important contribution to neuropathy and will be further discussed below.

The Importance of n-6 EFA’s

Dietary linoleic acid (LA, C18:2 w -6), passes through sequential steps of desaturation and elongation producing a variety of beneficial metabolites such as the prostaglandin (PGE) precursors dihomogammalinolenic acid (DGLA, C20:3 w -6) and arachidonic acid (AA, C20:4 w -6) which are important constituents of the phospholipids of neuronal membranes. The first step in the metabolism of LA, D -6-desaturase to gamma linolenic acid (GLA, C18:3 w -6) is impaired in diabetes (especially Type I)1, 2, resulting in normal or elevated LA levels3 and in reduced conversion to DGLA and AA. The enzyme D -6-desaturase is inhibited by glucagon and glucose but stimulated by insulin. Impaired incorporation of the EFAs into cell membranes applies equally to both types of diabetes. Reduction in these EFAs and the prostaglandins (series 1 & 2) derived from them cause a variety of microvascular, haemorrheological, nerve conduction4 and other abnormalities, leading to reduced blood flow and neuronal hypoxia. Generation of oxygen-free radicals escalates the hypoxia, leading to neural capillary endothelial damage and subsequent impairment of axonal transport, eventual demyelination and reduced neural ATP-ase activity5. The reduced prostaglandin production may lead to vasoconstriction, platelet aggregation, reduced insulin secretion & sensitivity and hyperglycaemia. EFA deficiency cause capillary defects similar to those occurring in diabetic nerves. DGLA & AA are important for nerve structure and function. AA also promotes insulin secretion and DGLA potentiates insulin effects on lipogenesis in adipocytes.


GLA (480 mg/day) administration, in the form of a variant of evening primrose oil (6 g of EPO: SC-1100) to patients with Type I diabetes, prevented deterioration of mild diabetic polyneuropathy (neuronal phospholipids structure) even reversing the condition6, 7 and improved the microcirculation8 (reduced blood viscosity, platelet activation and increased red blood cell membrane viscosity). Further studies showed statistical significant improvement on 28 neurological parameters (especially motor & sensory nerve conduction velocity) after supplementation, when compared with a placebo group9,10. These GLA studies were confirmed in rats with experimental diabetes mellitus, which prevented nerve ischaemia11, corrected nerve conduction12 and normalized impaired production of nitric oxide13. The improvement in neurological function was independent of diabetic control as GLA has no effect on glycosylated haemoglobin levels. GLA also reduces calcium excretion, triglycerides and cholesterol.


Diabetic patients are at risk of developing retinopathy and neuropathy and may require much higher amounts of linoleic acid to provide long-chain PUFA's (GDLA & AA). Direct supplementation with GLA avoids the first rate limiting step (D -6-desaturase). All studies have confirmed the safety of GLA treatment, which clearly improves both subjective symptoms and functional parameters in symptomatic diabetic neuropathy.



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