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

 

Introduction

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.

Supplementation

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.

Conclusion

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.

 

References

  1. Jones, D.B. et al. Low phospholipids arachidonic acid values in diabetic platelets. BMJ. 1983; 286: 176 – 175.
  2. Horrobin, D.F. Essential fatty Acids in the Management of Impaired Nerve Function in Diabetes. Diabetes. 1997; 46, Suppl., 2, S90 – S93.
  3. Tilvis, R.S. & Miettinen, T.A. Fatty acid composition of serum lipids, erythrocytes and platelets in insulin-dependent diabetic women. J. Clin. Endocr. Metab. 1985; 61: 741 - 745.
  4. Horrobin, D.F. et al. Prostaglandin E1 modifies nerve conduction and interferes with local anaesthetic action. Prostaglandins. 1977; 14: 103 - 110.
  5. Jamal, G.A. The use of Gamma linolenic Acid in the prevention and treatment of Diabetic Neuropathy. Diabet. Med. 1994; 11: 145 – 149.
  6. Keen, H. et al. Treatment of diabetic neuropathy with g -linolenic acid. Diabetes Care. 1993; 16: 8-15.
  7. Horrobin, D.F. The roles of essential fatty acids in the development of diabetic neuropathy and other complications of diabetes mellitus. Prostag. Leucot. E.F.A Rev. 1988; 31: 181 – 197.
  8. Jamal, G.A. Pathogenesis of diabetic neuropathy: the role of the n-6 fatty acids and their eicosanoids derivatives. Diabet. Med. 1990; 7: 574 – 579.
  9. Jamal, G.A. & Carmichael, H. The effect of g -linolenic acid on human diabetic peripheral neuropathy: a double-blind placebo-controlled trial. Diab. Med. 1990; 7:319 - 323.
  10. The g -Linolenic Acid Multicenter Trial Group:. Treatment of diabetic neuropathy with g -linolenic acid. Diab. Care. 1993; 16: 8 - 15.
  11. Stevens, E.J. et al. Essential fatty acids treatment prevents nerve ischaemia and associated conduction anomalies in rats with experimental diabetes mellitus. Diabetologia. 1993; 36: 397 - 401.
  12. Cameron, N.E. & Cotter, M.A. Potential therapeutic approaches to the treatment or prevention of diabetic neuropathy: evidence from experimental studies. Diabet. Med. 1993; 10: 593 - 605.
  13. Omawari, N. et al. Deficient nitric oxide is responsible for reduced nerve blood flow in diabetic rats: prevention by essential fatty acids (Abstract). Br. J. Pharmac. 1995; 116: 63.