This Dutch study was conducted to determine whether Minoxidil has an inhibitory effect on certain enzymes involved in collagen synthesis.
Collagen is the most abundant protein in the human body and provides stability and, to some extent, elasticity. It’s a common structural protein that can be found in bone, skin, tendons and blood vessels and gives both strength and flexibility to these biological structures. The protein can be visualized like a rope twined from 3 smaller ropes. This triple-helix structure gives collagen its properties with each “rope†consisting of many amino acids in a string. The most common amino acids present are proline and glycin, but hydroxyproline and hydroxylysine can also be found, the latter two provide stability to the helix through hydrogen bonds and cross-linking.
In men suffering from androgenetic alopecia, male pattern baldness (male pattern baldness), it’s common to find perifollicular fibrosis (PF). Perifollicular fibrosis is when the collagen surrounding the follicle becomes rigid and forms a scar-like capsule around the follicle, cutting it off from circulation, and thus nutrition.
This condition is time dependent, the closer to the onset of male pattern baldness the less PF-affected follicles you will find. This then increases with the passing of time and is why long-term hair loss sufferers generally respond poorly to hair loss treatments.
PF can also occur from mechanical trauma, like when you pluck (or wax) your hair. When the anagen hair is pulled up from the follicle it can cause damage and formation of scar tissue. This is why frequently plucked hairs may grow smaller and smaller with time, because it gets less and less nutrition.
Collagen in these rigid formations often shows a higher content of hydroxyallysine cross-links. Hydroxyallysine is a modified version of hydroxylysine, hydroxylysine is in turn formed through the action of lysyl hydroxylase (LH).
When lysyl hydroxylase is inhibited, hydroxylysine isn’t formed, and therefore no hydroxyallysine is either, this then leads to an unstable triple-helix and weak collagen structures. This happens in scurvy, a condition caused by a lack of vitamin C, since lysyl hydrolyxase needs vitamin C to work.
It has been suggested that if LH could be inhibited to form less hydoxylysine in fibrose tissue, it would then become less rigid and would not cut off the nutrition to the follicle. Some scientists have postulated that minoxidil works through this exact mechanism, by stopping follicular fibrosis and by providing the affected follicles with more nutrition by stimulating angiogenesis (the formation of blood vessels).
This study examined minoxidil’s inhibitory effect on LH and how that affected collagen synthesis.
The study found that minoxidil reduced LH1 much more than LH2b and LH2b, and more than LH3 in a time- and dose-dependent manner in fibroblasts in vitro (in a Petri dish), but still had no effect on the formed hydroxyallysine cross-linked in the collagen.
A possible explanation for this is that minoxidil had the most suppressive effect on LH1, which is thought to have a preference for triple-helical lysine residues. To reduce the number of hydroxyallysine cross-links one needs to only reduce hydroxylation of lysine at the end of the proteins, the telopeptides, and very little in the helix itself. The hydroxylase thought to be responsible for this is LH2b, and that wasn’t suppressed as much by the minoxidil. One theory is that LH2b is only needed in small amounts to hydroxylate enough telopeptide lysine residues, and/or that it does so in conjuction with LH3.
The researchers concluded that it’s unlikely that minoxidil works by acting as an anti-fibroticum, but they did confirm minoxidil’s inhibitory effect on the lysyl hydroxylases. The study also provided additional information about the different lysyl hydroxylases, which may prove useful in further studies.
