User:Logan Rutherford

Metabolism and Eicosanoids



The first step in the metabolism of Linoleic Acid (LA) is performed by Δ-6-desaturase, which converts LA into Gamma Linolenic Acid (GLA).

LA is able to perform at least some of its functions without metabolism. For instance, by itself it maintains the water impermeability of the skin. However, most functions do require its conversion to GLA. This has interesting consequences vis-à-vis bottle-fed babies: breast milk contains GLA, while some formulas contain only LA. Breast milk fed babies have higher concentrations LA metabolites than bottle-fed babies, leading some to hypothesize that infants’ desaturase activity is inadequate for optimal health.

GLA is converted to Dihomogamma Linolenic Acid (DGLA), which in turn is converted to Arachidonic Acid (AA). One of the possible fates of AA is to be transformed into a group of metabolites called eicosanoids, a class of paracrine hormones. The three types of eicosanoids are prostaglandins, thromboxanes, and leukotrienes. Eicosanoids are only produced from AA and tend to be pro-inflammatory.

For example, both Thrombaxane and LeukotrieneB4 are proaggretory and vasoconstrictive eicosanoids. An increased intake of Omega 3 fatty acids with a decrease in Omega 6 fatty acids has been shown to attenuate inflammation due to reduced production of these eicosanoids.

One study monitoring two groups of survivors of myocardial infarction concluded that “the concentration of alpha-linolenic acid was increased by 68%, in the experimental group, and that of linoleic acid reduced by 7%...the survivors of a first myocardial infarction, assigned to a Mediterranean alpha-linolenic acid rich diet, had a markedly reduced rat of recurrence, other cardiac events and overall mortality.”

Possible Roles in Disease

Cancer Prevention

A study in mice has shown that dietary intake of Conjugated Linoleic Acid (CLA) can help prevent cancer in mice. The study looked at a specific isomer of LA and studied its effect on cancer induced by dimethylbenz(a)anthracene. The study suggested a significant effect of CLA intake on the reduction of carcinogenesis.

Cystic fibrosis

Since children with cystic fibrosis suffer from Essential Fatty Acid Deficiency due to malabsorption, it was hypothesized that high doses of LA might aid in their growth. The study looked at two groups of infants with cystic fibrosis on diets with two different levels of LA. It was shown that supplementary LA, indeed, has a positive effect on the growth of infants with cystic fibrosis, especially between 6 and 9 months of age.

Multiple sclerosis

Initial studies on the effect of unsaturated fatty acids on MS have shown conflicting results. However, a meta-analysis of three studies indicates that LA intake might have a positive impact on the development of the disease in MS patients. It is hypothesized that LA plays its role by reducing pro-inflammatory cytokines in the blood of patients and as a result has a modulatory effect on inflammation. It is this anti-inflammatory effect that might play the role in combating autoimmunity in MS patients.

Dermatitis

Dermatitis is one of the first signs of an Essential Fatty Acid deficiency in both humans and animals. Until 1955, one of the most widely applied treatments for atopic eczema was a high dose of LA.

Diabetes

A number of studies have shown that diabetics require higher than normal intakes of LA. Because diabetics have consistently been shown to have above normal levels of LA while having lower than normal levels of LA metabolites, it is believed that diabetics have impaired Δ-6-desaturase activity. Increased intakes of LA have been shown to attenuate diabetic complications in numerous studies.

1- Mammary Cancer Prevention by Conjugated Dienoic Derivative of Linoleic Acid Cancer Research 51, 6118-6124, November 15, 1991

2- Effect of linoleic acid intake on growth of infants with cystic fibrosis, The American Journal of Clinical Nutrition, 1996, vol. 63, no5, pp. 746-752.

3- Multiple sclerosis and nutrition. http://msj.sagepub.com/cgi/reprint/11/1/04

4- David F. Horrobin (1993).“Fatty acid metabolism in health and disease: the role of   Δ-6-desaturase.” American Journal of Clinical Nutrition. 57: 732S-7S.

5- Piomelli, Daniele (2000). "Arachidonic Acid". Neuropsychopharmacology: The Fifth Generation of Progress. http://www.acnp.org/g4/GN401000059/Default.htm. Retrieved on 4/16/09.

6- John E. Kinsella, Belur Lokesh, and Richard A. Stone (1990) “Dietary n-3 polyunsatruated fatty acids and amelioration of cardiovascular disease: possible mechanisms.” American Journal of Clinical Nutrition. 52: 1-28.

7- Michel de Lorgeril, and Serge Renaud (6/11/94). “Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.” Lancet 343: 8911.