Migraine, Heparin, Glucosamine

Is it possible to repair the damage that leads to migraine headaches? If chronic inflammation is a risk factor, then depletion of brain heparan sulfate proteoglycans could be repaired temporarily with heparin or gradually with glucosamine.

Mast cells, the secreters of histamine in allergic reactions, also secrete heparin at the same time. In fact, cattle and swine intestines are the sources of commercial heparin. The crude source of heparin became dangerously apparent in recent scandals over the adulteration of Chinese heparin raw materials with hypersulfated chondroitin sulfate. But why is heparin secreted along with histamine in mast cells and what does this have to do with migraine headaches and glucosamine?

A basic observation is that migraineurs who receive heparin or glucosamine treatments for other symptoms, see relief from their headaches. Heparin treatments can produce dramatic effects that may be shortlived. Glucosamine may require substantial amounts taken orally for four to six weeks before migraines abate. Heparin and glucosamine are both effective, but how do they work?

Heparin and glucosamine therapies are both awkward. Heparin is rapidly internalized and degraded by cells. Glucosamine is also rapidly taken up and processed. In both cases, ingested heparin or glucosamine do not enter the blood stream. I think it is highly unlikely that either taken orally will have their effects directly in the brain or joints, simply because they are commonly metabolized molecules. Glucosamine may be a building block for heparin and other glycosaminoglycans, but it just passes directly into glucose metabolism, so that logical connection is unimportant in joint pain or migraines. I covered glucosamine in more detail as an anti-inflammatory molecule in another article, so here I will only emphasize that glucosamine is very effective for prophylaxis of migraine headaches.

Heparin can have an impact orally for some bowel diseases, but for headaches it must be administered IV or by inhaling. The major point here is that heparan sulfate proteoglycans (proteins with long heparan polysaccharides) mediate most of the hormonal signaling by mediating the binding of hormones to their receptors. Heparan fragments, called heparin, are a mixture of molecules that may interfere with or augment signaling, dependent on the quality of the heparinoids and the signal pathways under consideration. In most cases, there are so many different hormones and receptors involved, that it is more straightforward to try heparin to see if it works, rather than attempt to sort out all of the side reactions. If heparin does work, it should also be noticed that the amount of heparin required for an anticoagulant effect is on the high side, reflecting the depletion of circulating heparin.

Mast cells and histamine release have been implicated in migraine, but we have to return to the question of why heparin is normally released at the same time. From my own experiments with chondrocytes, the cartilage secreting, developmentally related sisters of the arterial endothelial cells, I would expect that inflammation inhibits heparin synthesis. Prevailing inflammation may reduce the production of heparin by mast cells and neuronal cells. As a result, triggering mast cells may release histamine into heparin-depleted brain tissue. If heparin normally serves to control the spread of the inflammatory signal from mast cells, then the absence of adequate heparin may lead to a spreading inflammation, a kind of neurological shock and awe. Addition of circulating heparin may temporarily repair the blood brain barrier, just as it does the lining of the bladder with interstitial cystitis or the kidneys in diabetes or the intestines in protein lossing enteropathy.

It appears that migraines are based on chronic inflammation of the brain and an associated compromise of the blood brain barrier. The source of the chronic inflammation may be shared with other degenerative and autoimmune diseases that lead to migraine attacks. Underlying infections may be hard to identify. The solution is to reestablish the blood brain barrier by eliminating chronic inflammation. Separate reports indicate that glucosamine, omega-3 fatty acids and anti-oxidants are all effective in reducing migraines. It seems obvious that the first step would be to begin an anti-inflammatory lifestyle (including exercise, dental hygiene, etc.) supported by an appropriate diet.