Gamma-linolenic Acid (GLA) Supplementation For Diabetic Neuropathy
Gamma-linolenic acid (GLA), also called gamolenic acid is an essential omega-6 fatty acid. It is synthesized from linoleic acid, through the process of dehydration via an enzyme called d6 desaturase. Omega-6 fatty acids together with Omega-3 fatty acids are collectively known as polyunsaturated fatty acids (PUFAs). These are necessary to maintain optimal health by promoting skin and hair growth, increasing bone density and prevention of osteoporosis, and regulation of metabolism via the thyroid gland.
Despite being essential for normal functioning, these fatty acids are not endogenously produced by the human body. They must be obtained from exogenous nutritional sources. The most important sources of dietary GLA are hemp seed oil, evening primrose oil, and borage oil containing 5%, 10%, and 20% of GLA respectively. Black currant oil, which contains 15-20% of gamma linoleic acid, has a very limited market supply. Spirulina (often called blue-green algae) also contains GLA.
These fatty acids have different functions. Omega-3 fatty acids help reduce inflammation while some omega-6 fatty acids like linoleic and arachidonic acid promote inflammation. An exception to this is the Gamma-linolenic acid, which has anti-inflammatory properties. Due to this, GLA had the reputation of being the good omega-6 fatty acid. A balanced consumption of Omega-3 and Omega-6 fatty acids is essential.
Innate synthetic dilemma of GLA
Despite the abundance of linoleic acid from food sources such as vegetable oil and animal fat, the production of gamma-linoleic acid is still lower than what is required by the body. This is largely due the impaired activity of the enzyme d6 desaturase, which manufactures it from linoleic acid. Biochemical studies done on this enzyme prove that it is highly unstable and its concentration in most tissues is low, if not difficult to establish. D6 desaturase activity is particularly impaired amongst diabetics. Other factors associated with impaired enzymatic activity are aging, stress, alcoholism and smoking.
Apart from this innate predicament in biosynthesis, the metabolism of gamma-linolenic acid is also problematic. Once manufactured, it is readily degraded into its byproducts other fatty acids in the PUFA pathway, namely di-homo-gamma linoleic acid (DGLA) and arachidonic acid. This may be the reason why tissue concentrations of gamma-linolenic acid remain low despite the abundance of its precursor for the modern diet.
GLA and its role in nerve repair
Diabetic neuropathy is seen in half of patients with diabetes. It is a debilitating disease, which causes various problems such as orthostatic hypotension, silent cardiac ischemia, hyperhidrosis, vasomotor instability, gastroparesis and motor deficits.
This type of neuropathy has two stages of pathogenesis. First, hyperglycemia among diabetics has serious biochemical sequelae, wherein there is increased protein glycation and free radical attack causing nerve damage. Second, there is impaired production of nitric oxide in the nerve fiber covering. Nitric oxide is important for blood vessel dilatation and ultimately perfusion of the nerves. Impairment of nitric oxide production leads to impaired delivery of nutrients to the nerve sheath, causing nerve damage.
Seventy to eighty percent of the human nervous system is composed of lipids.
Research suggest that the impairment of our innate impaired production of gamma linolenic acid lead to defective nerve function because metabolites of GLA are known to be important in nerve membrane structure, neurovascular function, and nerve conduction. Hence, since the early 1990’s, investigations regarding gamma linoleic acid supplementation and its effect on diabetic animal models have been well documented.
It is worth mentioning that extensive studies on these have been made by the late, David Frederick Horrobin. He is a strong advocate of fatty acid supplementation and is the founder of a biotechnology company, which promotes primrose oil supplementation. He conducted research which hypothesizes that gamma linoleic acid supplementation corrects impaired nerve function in animal models of diabetes.
To date, there are several multi-center, randomized, placebo-controlled trials in humans with diabetic neuropathy. These studies have shown significant benefits of gamma-linoleic acid supplementation as compared with placebo in neurophysiological parameters, neurophysiologic thresholds, temperature studies and clinical sensory evaluations. Improvements is nerve conduction studies provide a strong evidence that supplementation could be beneficial in preventing diabetic neuropathy.
Current recommendations for diabetic neuropathy
Strict blood sugar control by regular monitoring and optimal medication compliance is central to the primary prevention of diabetic neuropathy. Gamma linoleic acid and alpha-lipoic supplementation are also recommended to prevent diabetic neuropathy. Among other substances, controlled trials prove that these two substances were found to decrease the neurologic disability score amongst patients with diabetic neuropathy, as evidenced by improving nerve conduction studies.
Patient and their families should be counseled and emphasis regarding self-preventive measures should be undertaken. Early referral to specialist care and therapeutic foot ware can prevent foot ulceration from diabetic neuropathy. This will improve the quality of life and lower health care costs from this chronic disease.
References:
- Horrobin DF (1997) Essential fatty acids in the management of impaired nerve function in diabetes. Diabetes 46:S90 –93
- Jamal, G.A. and Carmichael, H. (1990), The Effect of γ-Linoleic Acid on Human Diabetic Peripheral Neuropathy: A Double-blind Placebo-controlled Trial. Diabetic Medicine. 7: 319–323. doi: 10.1111/j.1464-5491.1990.tb01397.x
- Cho, H., Nakamura, M., Clarke, S. (1999), Cloning, Expression, and Nutritional Regulation of the Mammalian ∆-6 Desaturase. J. Biol. Chem. 274:471-477. doi: 10.1074/jbc.274.1.471.
- Keen, H et al (1993) Treatment of diabetic neuropathy with gamma-linoleic acid. The gamma-Linolenic Acid Multicenter Trial Group. Diabetes Care.1993 Jan;16(1):8-15.
- Morell P, Quarles RH (1999), Characteristic Composition of Myelin. In: Siegel GJ, Agranoff BW, Albers RW, et al., editors. Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition. Philadelphia: Lippincott-Raven; 1999. Available from: http://www.ncbi.nlm.nih.gov/books/NBK28221/
- Senthil, K et al. (2013). Primary and Secondary prevention od diabetic neuropathy: an update. Indian Journal of Preventive Medicine. 2013 Jan-June 1(1).
- Coste TC, Gerbi A, Vague P, Pieroni G, Raccah D. Neuroprotective effect of docosahexaenoic acid-enriched phospholipids in experimental diabetic neuropathy. Diabetes. 2003;52:2578–85.
- Pitel, S, et al. At Low Doses, a g-Linolenic Acid-Lipoic Acid Conjugate Is More Effective Than Docosahexaenoic Acid-Enriched Phospholipids in Preventing Neuropathy in Diabetic Rats. Journal of Nutrition. 137: 368–372, 2007.
- Partial Replacement with Menhaden Oil Improves Peripheral Neuropathy in High-Fat-Fed Low-Dose Streptozotocin Type 2 Diabetic Rat
http://www.hindawi.com/journals/jnme/2012/950517/ - Gamma-Linolenic Acid (GLA)
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