The endocannabinoid signaling system: a marriage of PUFA and musculoskeletal health (A Review)
Journal Title (Medline/Pubmed accepted abbreviation): J. Nutr. Biochem.
Year: 2010
Volume: 21
Page numbers: 1141-1152
doi (if applicable): 10.1016/j.jnutbio.2010.04.011
The endocannabinoid (EC) system is an endogenous pathway that has only recently been studied in detail. It is known to be involved in appetite and more recent evidence suggests that it is involved in glucose metabolism and insulin regulation. Endogenous cannabinoid receptor agonists include anandamide (AEA) and 2-arachidonoylglycerol (2-AG) which are synthesized from arachidonic acid, an omega-6 fatty acid. Delta-9 tetrahydrocannabinoid (THC) is an exogenous activator of the cannabinoid system and is found in marijuana. There are two primary cannabinoid receptors, CB1 and CB2. AEA, 2-AG, and Δ-9-THC bind to CB1with higher affinity than CB2. CB1 is present in skeletal muscle and it has been shown that AEA interferes with glucose uptake due to mechanisms that reduce insulin sensitivity. There is also evidence that substrates that bind the CB1decrease fatty acid oxidation in skeletal muscle. Moreover, an increase in CB agonists increases glucose uptake, and triglyceride synthesis in adipose tissue, leading to an unhealthful body composition and eventually obesity.  The cannabinoid system also plays an important role in bone formation. CB2 is populous in bone cells and it has been shown that low levels of AEA and 2-AG are associated with increased bone loss in mice, although higher levels may have an opposite effect due to nonspecific interactions with other pathways. 
With regard to muscle health, the authors hypothesize that omega-3 polyunsaturated fatty acids (PUFAs) can reduce CB agonist concentrations, thus leading to increased insulin sensitivity, increased glucose uptake by skeletal muscle, increased fatty acid oxidation by skeletal muscle, etc, therefore having similar beneficial effects as exercise. There is direct evidence that an increase in omega-3/omega-6 polyunsaturated fatty acids (i.e. and increase in the consumption of omega-3’s without increasing total fat intake) may aid in bone formation in growing rats. Docosahexaenoic acid (DHA) has been shown to be the most effective in supporting bone formation and preventing bone loss. DHA replaces some arachidonic acid in tissues, thereby reducing the flux through the EC pathway. The interconnections among omega-3 and omega-6 fatty acids, prostaglandins, endocannabinoid signaling and bone formation are still being elucidated. 

Interpretation of findings/Key practice applications:

 It is important to have habitual omega-3 fatty acid intake in order to achieve maximum bone mass and strength, insulin sensitivity, substrate utilization by skeletal muscle, and crosstalk between muscle and bone in order to glean maximal benefits from exercise.

Limitations of the review:

This research is only in its infancy and there is a lot of information in this review that is simply speculative. There are a lot of associations between endocannabinoids and biomarkers but mechanisms are still poorly defined. It is likely that the relationship between the EC system and musculoskeletal health will not be completely understood for some time, but this article raises interesting connections and possibilities for future study.
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