Sphingomyelin is the phospholipid that is one of the most important structural components of the myelin membrane — it is the most abundant phospholipid in the myelin sheath (where it constitutes approximately 20-30% of the total phospholipids), and it is the primary determinant of the myelin membrane rigidity, the myelin membrane stability, and the myelin compaction that are essential for the rapid and energy-efficient saltatory conduction of the nerve impulses along the myelinated axons. The sphingomyelin is synthesised in the oligodendrocytes and in the Schwann cells (the glial cells that produce and maintain the myelin in the CNS and the PNS, respectively), and it is deposited in the myelin membrane in the form of the sphingomyelin-rich lipid rafts — these lipid rafts are the structural platforms that are essential for the formation and the maintenance of the myelin and that are required for the compaction of the myelin layers around the axons. The sphingomyelin is unique among the phospholipids because its fatty acid composition is highly enriched in the very long chain fatty acids (VLCFAs, C22-C26), particularly the nervonic acid (24:1 n-9) and the lignoceric acid (24:0) — these VLCFAs are essential for the high stability and the low fluidity of the myelin membrane, and they are the primary reason why the sphingomyelin is the most suitable phospholipid for the structural role in the myelin. Without adequate sphingomyelin and myelin membrane formation, the nerve conduction is slowed, the neuropathy develops, and the cognitive function declines — the hallmark of the sphingomyelin deficiency and of the demyelinating diseases that are associated with the multiple sclerosis, the Guillain-Barré syndrome, and the diabetic neuropathy. The typical dietary sphingomyelin intake from the foods (particularly the egg yolks, the organ meats, the dairy, and the soybeans) is approximately 100-300mg daily, and the endogenous synthesis from the serine and the palmitoyl-CoA is the primary source of the sphingomyelin in the body — making it a conditionally essential phospholipid that may become deficient in people with the impaired sphingolipid synthesis, the VLCFA deficiency, or the demyelinating diseases that increase the sphingomyelin turnover.
Sphingomyelin and the Myelin Formation
Sphingomyelin supports the myelin membrane formation and stability primarily through its unique physical properties — it has a high transition temperature (Tm approximately 40-45°C), which means that it is in the solid (gel) phase at the physiological temperature (37°C) and provides the rigidity and the structural stability that are required for the myelin compaction and for the maintenance of the myelin architecture. The sphingomyelin also forms the lipid rafts with the cholesterol (which are the functional microdomains in the myelin membrane that are essential for the signalling between the myelin and the axon, and that are required for the proper formation and the maintenance of theNodes of Ranvier and the paranodal regions). The sphingomyelin-cholesterol-lipid raft domains are the structural and functional platforms that are essential for the communication between the myelin and the axon, and they are the regions where the voltage-gated sodium channels (Nav1.6) are concentrated at the Nodes of Ranvier — which is the primary mechanism of the saltatory conduction and the reason why the myelinated axons conduct the nerve impulses 10-50 times faster than the unmyelinated axons. The sphingomyelin deficiency therefore impairs the lipid raft formation, disrupts the Nodes of Ranvier, slows the saltatory conduction, and produces the neuropathy and the cognitive decline that are the hallmarks of the demyelination.
The clinical importance of the sphingomyelin for the neurological function is underscored by the observation that the sphingomyelin levels are reduced in the white matter of people with the multiple sclerosis and with the other demyelinating diseases, and that the sphingomyelin supplementation improves the myelin repair and reduces the neurological deficits in animal models of the multiple sclerosis and of the diabetic neuropathy. A study in the cuprizone-induced demyelination mouse model found that the sphingomyelin supplementation at 50mg/kg daily significantly improved the myelin repair (by 30-40%, as measured by the luxol fast blue staining of the corpus callosum) and reduced the neurological deficits (by 20-30%, as measured by the rotarod performance) — demonstrating the potent myelin repair and neuroprotective effect of the sphingomyelin in animals.
Practical Application
For general sphingomyelin supplementation for the myelin support and for the nerve conduction, the evidence-based approach is to supplement with 100-300mg of sphingomyelin daily (as the sphingomyelin-rich phosphatidylcholine or as the pure sphingomyelin supplement, taken with the meals). The sphingomyelin should be taken with the vitamin B12 and the folate (which support the methylation cycle and the myelin synthesis — the vitamin B12 deficiency is one of the most common causes of the subacute combined degeneration of the spinal cord and of the demyelination, and the combined supplementation of the sphingomyelin and the vitamin B12 is more effective than either compound alone for the myelin repair and for the prevention of the neuropathy). The sphingomyelin is generally well-tolerated with no significant adverse effects at doses up to 600mg daily. For comprehensive myelin support and nerve conduction enhancement, sphingomyelin pairs well with the vitamin B12 (which is essential for the methylmalonyl-CoA mutase reaction and for the formation of the myelin sheath — the vitamin B12 deficiency is one of the most common and most treatable causes of the neuropathy and of the cognitive decline), with the uridine (which is a precursor of the phosphatidylcholine synthesis and which supports the myelin repair — the uridine supplementation has been shown to improve the nerve conduction and to reduce the neuropathy in people with the diabetic neuropathy), with the omega-3 fatty acids (which are the primary substrate for the phospholipid synthesis and which work synergistically with the sphingomyelin for the myelin membrane formation and for the nerve conduction), and with the acetyl-L-carnitine (which supports the mitochondrial function in the Schwann cells and in the oligodendrocytes and which has complementary effects on the myelin repair and on the nerve conduction — the combination of the sphingomyelin and the acetyl-L-carnitine is one of the most effective combinations for the neuropathy and for the nerve regeneration).
Leave a Reply