Reversing atherosclerosis with melanocortin stimulating hormone

High levels of melanocortin-stimulating hormone (commonly refereed to as a-MSH, aka the hormone that released to make you tan in response to UV light) may play a much more significant role than previously acknowledged in the management of atherosclerosis, particularly in the reabsorption of atherosclerotic plaques.

Stimulation of α-MSH through POMC precursor (POMC is part of the reason why I don’t think using things like melanotan works for this. You need to signal POMC and the genes it regulates with UV exposure rather than using the hormone directly) exhibits very potent anti-inflammatory properties and promotes homeostatic mechanisms that can lead to the regression of atherosclerotic lesions.

Another one of the predominant theoretical mechanisms by which α-MSH might facilitate the reabsorption of atherosclerotic plaques is through the promotion of reverse cholesterol transport and cholesterol efflux

Reverse cholesterol transport is the process of transporting cholesterol from peripheral tissues back to the liver for excretion. It involves the transfer of cholesterol to high-density lipoprotein (also known as HDL or ‘good cholesterol) particles, which carry it to the liver.

Cholesterol efflux is the specific mechanism by which cholesterol is removed from cells and transferred to HDL. This process is needed for maintaining cholesterol balance and preventing cardiovascular diseases. Both RCT and cholesterol efflux are essential for preventing heart disease and plaque accumulation

I’ve talked about RCT and CE before, particularly in the context of plasmalogens and heart disease. Plasmalogens supplementation and α-MSH production both appear to stimulate RCT and cholesterol efflux

α-MSH induces the expression of ATP-binding cassette transporters, specifically ABCA1 and ABCG1, which promote cholesterol efflux from macrophages. This reduces lipid accumulation within arterial plaques, promoting their regression

Some studies have shown that the expression of BOTH POMC and α-MSH is associated with plaque stability. Again, you need the sun for this. Not peptides like melanotan that only increase a-MSH.

In unstable plaques, the levels of α-MSH-producing enzymes are down-regulated, which I think could lead to reduced local availability of α-MSH. On the other hand, higher levels of systemic POMC and α-MSH have been correlated with more stable plaques, suggesting that enhancing α-MSH levels could be a therapeutic strategy to stabilize existing plaques and prevent cardiovascular events.

The hypothesis that cardiovascular disease is essentially an autoimmune condition (a sustained attack against the endothelium) may also have some relevance here to MSH and its impact on immune cells like macrophages. In the case of atherosclerosis, the immune system's response to lipid accumulation and endothelial injury directly resembles autoimmune processes, where immune cells target the vascular lining.

The melanocortin 1 receptor is another player in the immune system balance, particularly in the context of atherosclerosis. This receptor is expressed on immune cells as mentioned, including monocytes and macrophages. It directly mediates anti-inflammatory actions upon stimulation by its natural ligand (aka α-MSH). MC1-R signaling in atherosclerosis likely extends beyond mere anti-inflammatory effects — there appears to be an interplay between immune regulation in CVD and MC1

MC1-R activation has been shown to exert significant anti-inflammatory effects. And chronic inflammation causes lipid accumulation in arterial walls. The receptor's activation mitigates inflammatory processes that contribute to plaque formation and instability. We also know that MC1-R is involved in regulating the behavior of leukocytes, including their proliferation and migration into the vasculature. For instance, deficiency in MC1-R signaling has been linked to increased leukocyte counts and altered migration patterns of immune cells, particularly CD4+ T cells and monocytes. That dysregulation will exacerbate atherosclerosis by promoting the accumulation of pro-inflammatory cells and mediators in arterial plaques, causing plaque instability.

MC1-R also plays a role in cholesterol transport within macrophages, which is needed to prevent foam cell formation—a key event in atherosclerosis progression.

MC1-R activation helps maintain lipid homeostasis and appears to prevent the development of atherosclerotic lesions.

So the big question is, how do we stimulate MC1-R and a-MSH? Sun exposure. Not just any sun exposure. Mid-day, intense UVA light. UVA light specifically is what stimulates the release of a-MSH from the pituitary.

In order to stimulate MC1-R and a-MSH, your skin needs to TAN. This means that morning sun exposure (when the sun is mostly red light and the UV index is low) won’t do it. You need to be getting intense, mid-day UVA light without sunscreen. Obviously without burning. Build up exposure slow

Getting a slight tan is a good sign you’re likely producing enough a-MSH! It really is that simple. I think there could be a case to be made for people with severe plaque build up really trying to safely accumulate as much sun exposure as possible. If you live somewhere where the UV index is low most of the year, there could also be a solid case to be made for moving to a sub-tropical or lower latitude.

I always tell people to never go full jack kruse. But this is one instance where lots of sun exposure does seem to be a powerful tool to modify disease trajectory.