Alpha-MSH: Get Tan While Being Indoors…oh yeah and Deactivate Autoimmunity

What Is a-MSH and How To Increase It Naturally 

Alpha-Melanocyte Stimulating Hormone plays a role in many autoimmune, inflammatory, and chronic conditions. 




  1. Basics
  2. Benefits
  3. Downsides
  4. Caveats
  5. Increase a-MSH
  6. Decrease a-MSH
  7. Testing 
  8. Mechanism Of Action
  9. More Research


One main role of Alpha-Melanocyte Stimulating Hormone (a-MSH) is to increase melanocytes, which make you tan. R

Different levels of a-MSH are not the major cause of racial variation in skin color. R

However, in many red-headed people, and other people who do not tan well, there are variations in their hormone receptors, causing them to not respond to a-MSH in the blood. R

a-MSH Is High In

  • Addison’s R
  • Chronic Fatigue Syndrome R
  • Chronic Haemodialysis R
  • Congestive Heart Failure R
  • Cushing’s R
  • HIV R
  • Infections (like XMRV) R
  • Insulin Resistance R
  • Obesity R
  • Pregnancy R
  • Psoriasis R
  • Sepsis R

a-MSH Is Low In

  • Acute Brain Injury R
  • Alopecia R
  • Alzheimer’s Disease R
  • Anorexia (or being extremely thin) R R
  • Arthritis R
  • Binge Drinking Alcohol R
  • Bulimia R
  • CIRS R
  • HPA physical damage R
  • Multiple sclerosis R
  • Vitligo R


1. Ameliorates Autoimmunity


a-MSH can decrease the immune system’s response to lectins. R

Certain plant lectins contribute to autoimmunity. R

Encephalomyelitis (EAE) is an autoimmune disorder that inflames the brain and spinal cord. R R

a-MSH was able to inhibit T cells and stop the autoimmune attack of EAE on the central nervous system. R R

a-MSH can also be used to suppress autoimmune disease and possibly reestablish tolerance to autoantigens. R

It may also help against HIV. R

2. Helps Chronic Inflammatory Response Syndrome



Chronic Inflammatory Response Syndrome (CIRS) is an acute and chronic, systemic inflammatory response syndrome acquired following exposure to the interior environment of a water-damaged building with resident toxigenic organisms as well as Volatile Organic Compounds (VOCs). R

In CIRS, blocked leptin receptors will no longer create the initiation of steps that lead to production of a-MSH. R

Low a-MSH can cause sleep problems, “leaky gut”, chronic pain, and the ability for resistant staph (e.g. MARCoNS) to survive in biofilms on the mucous membranes. R

3. Improves Alzheimer’s Disease

Increased galanin and decreased α-MSH levels are seen in the brain and cerebrospinal fluid (CSF) of Alzheimer’s (AD) patients. R

Autoantibodies to galanin and a-MSH are also seen in the CSF of some AD patients. R

α-MSH treatment promoted the survival of GABAergic interneurons in the hippocampus and improved spatial memory as well as alterations in anxiety in a mouse model of AD. R

a-MSH also increases brain derived neurotrophic factor. R

4. Increases Love and Sex Drive



a-MSH can increase nitric oxide (NO) delivery, which helps blood flow and the vascular system. R

In men, a-MSH increases male libido (by binding to MC3R and MC4R receptors). R

It also contributes to erections. R R

In women, 24 hours after treatment, it increased sexual arousal and satisfaction. R

a-MSH can also stimulate oxytocin, the cuddle/love hormone, in the dendrites of the hypothalamic neurons. R 

a-MSH is selective on where oxytocin neurons are released. R

5. Helps Multiple Sclerosis

In Multiple Sclerosis (MS), abnormal a-MSH levels were found in over 70% of patients. 

This may support the idea that  MS may be associated with pineal failure and suggest, furthermore, that alterations in the secretion of alpha-MSH also occur during exacerbation of symptoms. R

Melatonin and a-MSH regulate the protective effect against demylenation. R

6. Protects the HPA-Axis


a-MSH can limit stimulation and inflammation from IL-1b on the hypothalamic-pituitary-adrenal (HPA). R R

Low a-MSH can decrease anti-diuretic hormone, leading to thirst, frequent urination, neurally-mediated hypotension, low blood volume, and electric shocks from static electricity. R

7. Supports the Thyroid

a-MSH stimulates thyrotropin-releasing hormone (TRH). R

TRH is the precursor to thyroid-stimulating hormone (TSH) and prolactin. R

It also increases T3 in obese male rats. R

8. May Help With Sleep

Lack of a-MSH causes sleep problems. R

a-MSH suppresses orexin, a hormone that keeps you awake, so may help to take a-MSH before bed. R

9. Is An Anti-Microbial

a-MSH exerts potent antibacterial activities against a wide variety of gram-positive and gram-negative bacteria, essentially present on the gastrointestinal tract. R

It has shown to fight:

  • Staphyloccucs aureus R
  • Candida albicans R
  • E. Coli R

Other neuropeptides, such as neurokinin 1 (NK1), neuropeptide y (NPY), and proenkephalin A (PEA), are reported to have antimicrobial properties. R

10. Restores Insulin Sensitivity

a-MSH is able to increase insulin sensitivity and glucose update, while decreasing liver glucose production. R

11. Helps with Weight Loss

a-MSH reduced food intake in women. R

Specifically, it helps reduce abdominal fat. R

a-MSH regulates aldosterone in rats. R

Interestingly, a-MSH increased food intake of arthritic rats.  R

12. Helps Arthritis

In arthritic rats, α-MSH decreased the external signs of arthritis and increased food intake. R

It also decreased hypothalamic expression of IL-1β, COX-2, proopiomelanocortin, and prohormone-converting (PC) enzymes PC1/3 and PC2 mRNA in arthritic rats. R

13. Is An Anti-Inflammatory 



a-MSH is an anti-inflammatory hormone. R

It helps build a tolerance to our own and foreign  protein (like E. Coli). R R

a-MSH lowers TNF-a (which causes inflammation). R R

Cyclic AMP response element-binding protein (CREB) can also be activated by melanocortin activation resulting in improved cell survival from metabolic and oxidative stress. R

14. Helps Skin Disorders

a-MSH can improve the skin’s defense against hapten exposure.

Melanocortin receptor agonists and α-MSH have also demonstrated anti-inflammatory and inhibitory effects in a number of inflammatory skin models including atopic dermatitis, psoriasis, and antigen-induced chronic allergic skin inflammation. R R R

In vitiligo, melanocytes have high amounts of inflammation and oxidative stress.  R

They also have high levels of IL-8. R

a-MSH reduces levels of IL-8 and is an anti-inflammatory. R 

It also restores melanocyte receptor function and re-pigments the skin. R R

MC1R agonists administered to human fibroblasts in vitro decreased collagen type I, III, and V production induced by TGF-β. R R

15. Prevents Binge Drinking

Binge drinking causes a significant reduction of a-MSH levels in the brain. R

Melanocortin (MC) receptor agonists can attenuate alcohol intake. R

MC receptor antagonists stop ethanol drinking in mice. R

MC receptor signaling protects against binge-like alcohol (BLA) drinking. R

16. Protects the Brain After Traumatic Brain Injury

In patients with traumatic brain injury, for instance, decreases in plasma a-MSH occur and are associated with worse outcome. R

a-MSH helped with stroke recovery. R

17. Helps with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease resulting in loss of self-tolerance with multiple organs, such as the kidney, skin, joints, and the central nervous system. R

Central nervous system-associated disease in SLE patients is mainly due to one of two pathophysiologic changes: thrombotic disease or generalized CNS inflammation. R

α-MSH and ACTH have anti-fever effects, one of the many of the symptoms in SLE. R R R 

a-MSH has difficulty crossing the Blood-Brain Barrier (BBB). R

In SLE, the BBB becomes more permeable. R

This allows a-MSH to lessen pro-inflammatory responses and reduce neuronal damage on the CNS in SLE. R R

18. Protects the Kidneys

MC1R has been identified and co-localized on podocytes in human kidney tissue. R

Activation of these receptors leads to immunomodulatory and renoprotective effects. R

Proteinuria (the presence of excess proteins in urine), was significantly reduced by α-MSH. R

In models of kidney failure and inflamed kidney cells, a melanocortin agonist was able to stop the death of those cells. R




1. May Make Chronic Fatigue Syndrome Worse



a-MSH is usually higher in chronic fatigue syndrome (CFS) patients. R

α-MSH may be a biomarker for CFS in patients who have suffered from the disease for less than 5 years. R

Rats modeled with CFS were subjected to continuous stress for 5 days. They had hyper-secretion of a-MSH, but after 5 days then a-MSH levels droppedR

Hypothetically, melanotrophis in humans with CFS may become used up or impaired after prolonged stress. R

Dopamine synthesis is suppressed in some hypothalamic neurons in CFS patients, and melanotrophs may thus be hyper-activated. R

Or it may be that they just become desensitized. 

Patients with CFS usually have flushing, lower blood pressure, and increased pain. a-MSH can cause these. R

a-MSH also decreases weight, which many CFS patients have problems gaining weight. R

Stress can exacerbate CFS and increase MSH production (from the pituitary gland). R R

a-MSH suppresses orexin, which is a hormone that keeps you awake. R

2. Can Cause Depression

a-MSH increases prolactin.

High prolactin in males can cause depression. R

a-MSH increases Corticotropin-Releasing Hormone (CRH). R

Also a-MSH may be elevated in depression due to both low melatonin levels and hypersecretion of CRH. R

Administration of an a-MSH inhibitor has shown to significantly improve depressive symptoms. R

3. Can Cause Stress and Anxiety

CRH is the precursor to Adrenocorticotropic Hormone (ACTH) and cortisol. R

a-MSH activates the MC4R in the amygdala. R

This activates the HPA axis and can cause anxiety and reduce appetite. R

a-MSH also lowers GABA, which is necessary for feeling calm. R R R

If anxiety is brought on by inflammation, such as IL-1b, then a-MSH could theoretically decrease anxiety by decreasing inflammation. R



a-MSH can contribute to opioid tolerance, making pain killers (such as morphine) less effective. R

Anorexia and Bulimia

Anorexia nervosa (AN) has been proposed to be an autoimmune disease. R

Specifically it is caused by delayed exposure to common micro-organisms in which auto-antibodies to regulatory peptides and hypothalamic neurons, which cross react with microbial antigens, disturb appetite and lead to decreased intake of food. R

Good and bad E. Coli are naturally found in the gut. R

They have proteins that can confuse the gut causing antibodies to a-MSH. R

Anorexic patients may have autoantibodies to a-MSH, causing them to be skinny. R

Antibodies to a-MSH (along with ACTH, and LHRH) have been correlated with both AN and bulimia nervosa (BN). R R


Histamine intolerance symptoms are very similar to high a-MSH receptor activity. R

MC4R activation can cause fatigue, weight loss, lower blood pressure, increase pain, and flushing. R


If you sunburn easily, it could be from low MSH, or even low NAD+. R R


Since stress raises a-MSH temporarily, it can also increase antibodies to a-MSH which will lower it. R 

Increase Alpha-MSH

These are some ways to increase a-MSH.





  • Adiponenctin R
  • Corticotropin-Releasing Hormone R
  • Estrogen R
  • Insulin R
  • Leptin R R R R
  • Lower Dopamine R
  • Metharmon-F (Sex steroid-thyroid hormone) R
  • Resistin R
  • Thyrotopin Releasing Hormone R


  • α-Amidating Monooxygenase R
  • Carboxypeptidase E R
  • Cyclic AMP R
  • FOXO1 Activation R
  • N-Acetyltransferase R
  • STAT3 R


  • Gold Based Implants (made for regulating diabetes could inject a-MSH) R

Decrease Alpha-MSH

These are some ways to decrease a-MSH.

Lifestyle/ Diet


  • Dopamine R
  • GABA R
  • Ghrelin R
  • Low Leptin R
  • Melanocyte-inhibiting factor R
  • Melatonin R


  • Semax (It may antagonize a-MSH at the MC4R and MC5R sites. It has been shown to not antagonize a-MSH at the MC3R and it is unknown how it interacts with MC1R and MC2R. I find this information interesting as when I consistently take Semax I do get a darker skin tone. So take this bullet point with a grain of salt. It may also work on MIF instead, creating it’s anti-depressant effects.) R


  • AgRP R
  • NPY (by inhibiting POMC) R R
  • PRCP R
  • SIRT1 activation R


  • CIRS R
  • Removal of the Pituitary Gland R




My a-MSH Levels

I have always had low weight and a harder time in gaining weight. My a-MSH levels are at 13 pg/mL. This lower level even accounts for that I was in the sun for at least 3 hours each day. Here are some factors as to why I have had low a-MSH.

  • When living in Boston, I never got sun. Sun increases a-MSH. R
  • I did Doctor’s Data’s comprehensive parasitology test x3. It showed I have high amounts of “beneficial” E. Coli.
  • This may mean I have anti-bodies to a-MSH. R
  • I have high levels of IL-8, which may impair a-MSH production (through modulating NF-kappa B and AP-1). R

I tried an experiment to see how the sun affected my a-MSH levels. I cut my time to only 1 hour in the sun per day. After only a few months my a-MSH levels dropped to 7 pg/mL. I could feel the effects. Now I am in the process of bringing this back up to above 13 pg/mL.

Healthy a-MSH Levels

Dr. Shoemaker believes people with Chronic Inflammatory Response Syndrome (CIRS), be at least 35-81 pg/mL. 

This number doesn’t seem to make sense as I haven’t seen any studies that show healthy MSH levels to be that high

For example:

  • In a study of 30 healthy vs CFS, healthy levels of a-MSH have been shown to be 14.5 pg/mL. R
  • 17.9 was for people with CFS. R
  • Tramautic brain injury (TBI) patients had levels of 10.4 pg/mL. R
  • Subarachnoid hemorrhage had levels of 6.9 pg/mL. R
  • Healthy controls have also shown to have levels of 21-22 pg/mL. R
  • People with stroke had 12.8 pg/mL. R

Check Your a-MSH Levels

You can check your alpha-MSH levels here.

Mechanism Of Action


Melanocyte stimulating hormones (MSH), also known as melanotropins or intermedins, are a family of peptide hormones/neuropeptides separated into 3 categories:

  1. Alpha-Melanocyte Stimulating Hormone (a-MSH)
  2. β-melanocyte-stimulating hormone (β-MSH),
  3. γ-melanocyte-stimulating hormone (γ-MSH) 

They are produced by cells in the intermediate lobe of the pituitary gland. R

Circulating α-MSH can originate from the pituitary gland and/or blood cells. R

It can also be produced by the skin (that’s what causes tanning). R 

α-MSH produced by neurons in the arcuate nucleus has helps regulate appetite and sexual behavior. R

α-MSH secreted from the intermediate lobe of the pituitary regulates the production of melaninR

Pro-opiomelanocortin (POMC) can be cleaved enzymatically into a-MSH. R

Adrenocorticotropic hormone (ACTH) can also be cleaved to form a-MSH. R


  • Inhibits antigen presentation and costimulation by DCs R
  • Stimulates IL-10 production R
  • Inhibits T cell proliferation R
  • Stimulates expansion of Treg cells R
  • Stimulates generation tolergenic DCs R
  • Decreases IL-1b, TNF-a, IL-8, and ICAM-1 (through inhibition of NF-kB) R
  • Reduces IFN-γ from T cells R
  • Increases TGF-B1 R

Melanocortin Receptors

Melanocortin receptors are expressed in many cells including astrocytes, microglia, endothelial cells, and neurons. R R R

  1. Melanocortin peptides bind with different affinities and selectivity to five identified melanocortin receptor subtypes (melanocortin receptors (MC1–5R) that are distributed on multiple cell populations distributed throughout the body. R
  2. The MC1R is involved in skin and hair pigmentation and immune cell regulation. R
  3. ACTH is the only melanocortin peptide that activates MC2Rs in the adrenal gland to stimulate glucocorticoid synthesis and release. R
  4. MC3R regulates immune cell function. R
  5. Both MC3R and MC4R have roles in energy homeostasis and regulate neuronal interactions with autonomic functions. R R R
  6. The MC5R is expressed on a broad range of tissues throughout the body, but its function remains to be fully elucidated, although this receptor has been implicated in sebaceous gland function and in the stress response, based on its primary expression in exocrine glands. R

By inhibiting NF-kB, a-MSH prevents NF-κB from translocating to the nucleus and driving pro-inflammatory mediator transcription. R R

Melanocortin receptors also act on ERK1/2 signaling, Jak/STAT signaling, and AP-1 transcription R R R 

More Research

  • Semax may antigonise a-MSH at the MC4R and MC5R sites. It has been shown to not antogonise a-MSH at the MC3R and it is unknown how it interacts with MC1R and MC2R.
  • In some animals, MSH is increased when the animal is in a dark location (making skin get darker and harder for predators to spot). It is often called melanophore-stimulating hormone. 
  • MSH decreases ADH/Vasopressin in rat studies. R