Your Oral and Topical Minoxidil is not working
Minoxidil is a pro drug it needs conversion to work it is mainly converted by a enzyme known as SULT1A1( SULFOTRANSFERASE ENZYME ) this enzyme exist in hair follicles
Work of MINOXIDIL
1. Prolongs Anagen phase (growth phase)
2. Shortens Telogen phase (shedding phase)
3.Follicle Cell proliferation (growth of cell at hair follicle)
4. Upregulates VEGF ( Vascular Endothelial Growth Factor) formation of new blood vessel
5. Active nutrients transportation
6.Blood vessel widens more blood flow
i guess every one knows this lets get to the real deal
Minoxidil is inactive it self and is a neutral molecule when we apply or use minoxidil. SULT1A1 in hair follicle binds with minoxidil to form MINOXIDIL SULFATE ( ACTIVE FORM ) in this process SO3- binds with minoxidil via SULT1A1 enzyme and in simple terms the MINOXIDIL SULFATE opens ATP channel K+ ions rush out of cell this make cell more negative (hyper polarization ) hyperpolarized cell = relaxed cell which means blood vessel relaxes and widens blood flow
Low SULT1A1 = barely any conversion = poor response
This is genetically determined but can be altered to some point:feelshah:
Some people genuinely cannot respond well to topical minoxidil no matter the dose
This is also why oral minoxidil mogs for some non-responders cause oral has much more SULT1A1 activity than topical
Question is how to maximize its production ?
Remember PAPS is the sulfate donor
No PAPS = no sulfonation regardless of enzyme levels
PAPS requires sulfur and ATP to synthesize
Low sulfur intake = limiting step
Direct inhibitors
Minoxidil itself at high doses can saturate and deplete PAPS
Using too much topical minoxidil = diminishing returns
Also many healthy polyphenols compete with or block sulfonation at liver but does little effect at hair follicle but it does
PAPS synthesis requires inorganic sulfate. Your body gets sulfate from:
MSM (Methylsulfonylmethane) A supplement for this has a weak effect for human ig research has only been conducted to rats but weak research has been done on humans
NAC (N-Acetyl Cysteine) raises cysteine which is imp for PAPS synthesis this mechanism works but is indirect works best by combining with minoxidil
Taurine sulfur containing
Dietary sulfur foods eggs, meat there are some vegetables but seriously who eats them
MSM is the most direct and bioavailable sulfate source for PAPS synthesis. but low rsearch
2. Support things for SULT1A1 enzyme
SULT1A1 needs cofactors to function properly:
Magnesium : involved in PAPS synthesis
B vitamins (especially B2/riboflavin) : sulfur metabolism
Selenium : supports sulfur enzyme activity generally
Zinc : general enzyme cofactor
but low potency for working with minoxidil
3. Thyroid Function
important
Thyroid hormones upregulate SULT1A1 expression
Hypothyroidism is associated with poor sulfonation
if you're a poor minoxidil responder you might have bad thyroid
Tips : have good thyroid plus dont consume soylent food supplement MSM and NAC and will talk about its potency in next thread and avoid these polyphenols 2 to 3 hrs around application although the research is mostly done around SULT1A1 in liver cell for polyphenols and has a little effect on hair but has a effect .
Now ill be taking about MSM( Methyl Sulfonate methane )
MSM is a sulfur compound found in primitive plants ,animal and humans it also can be chemically made but the quantity is low in plants and animal and other foods
PHYSICAL PROPERTIES
Colourless, Odorless and white crystalline solid
MAIN USE
Commonly used for joint health supplement and is a anti inflammatory drug
SIDE EFFECTS
Mild gastrointestinal pain, headaches, insomnia, or skin rashes. not extreme tho
WORKING MECHANISM
Methylsulfonylmethane (MSM) works primarily by modulating the body's response to inflammation and oxidative stress at the cellular and genetic levels It acts as an adaptable regulator rather than a direct blocker, influencing several key biological pathways simultaneously
HOW THIS WORK FOR HAIR ?
1.SULFUR DONATION
MSMis a bioavailable sulfur it can provide bioavailable sulfur for SULT1A1 enzyme activity
2. ENHANCED PENETRATION
MSM increases cell membrane permeability when used with minoxidil it will penetrate deeper into skin works via ion and membrane modulation
Take this drug more than 3g a day to work but not fix for working with minoxidil due to
Low research for human hair but we have mechanism
FDA approved drug
NEXT NAC ( N-acetylcysteine )
WORKING MECHANISM
1.OXIDATIVE STRESS REDUCTION
Spoiler
It neutralizes free radicals and reactive oxygen species (ROS) that can damage hair follicles and trigger premature transition to the shedding phase.
2.GLUTATHOINE SYNTHESIS
By providing cysteine NAC helps maintain high levels of glutathione in the follicle, which is essential for protecting the rapidly dividing cells in the hair bulb
3.Inhibiting Hair-Loss Signals
NAC can suppress certain inflammatory mediators like PGD2 and TGF-β, which are known to inhibit hair growth in conditions like androgenetic alopecia (AGA)
Side Effects
While generally well tolerated, high intake can cause gastrointestinal issues such as nausea, vomiting, or diarrhea
Can work with minoxidil really well no fixed dosages for hair while some common dosages is 600 to 1200 mg told by some physicians
TBH these can be potent but has low roi and now will be taking about some other ways to max the usages
1. MICRO NEEDLING : We all know use it 3 times a week for 2 min at a part
2. USING TOPICAL TRETINOIN
Tretinoin upregulates the sulfotransferase enzyme. This can convert non-responders into responders
Apply a thin layer of tretinoin (0.01% to 0.025%) to thinning areas before minoxidil use it 3 to 4 times per week
Minoxidil is a pro drug it needs conversion to work it is mainly converted by a enzyme known as SULT1A1( SULFOTRANSFERASE ENZYME ) this enzyme exist in hair follicles
Work of MINOXIDIL
1. Prolongs Anagen phase (growth phase)
2. Shortens Telogen phase (shedding phase)
3.Follicle Cell proliferation (growth of cell at hair follicle)
4. Upregulates VEGF ( Vascular Endothelial Growth Factor) formation of new blood vessel
5. Active nutrients transportation
6.Blood vessel widens more blood flow
i guess every one knows this lets get to the real deal
Minoxidil is inactive it self and is a neutral molecule when we apply or use minoxidil. SULT1A1 in hair follicle binds with minoxidil to form MINOXIDIL SULFATE ( ACTIVE FORM ) in this process SO3- binds with minoxidil via SULT1A1 enzyme and in simple terms the MINOXIDIL SULFATE opens ATP channel K+ ions rush out of cell this make cell more negative (hyper polarization ) hyperpolarized cell = relaxed cell which means blood vessel relaxes and widens blood flow
Why SULT1A1 Levels Matter So Much ?
High SULT1A1 in follicles = converts lots of minoxidil = great responseLow SULT1A1 = barely any conversion = poor response
This is genetically determined but can be altered to some point:feelshah:
Some people genuinely cannot respond well to topical minoxidil no matter the dose
This is also why oral minoxidil mogs for some non-responders cause oral has much more SULT1A1 activity than topical
Question is how to maximize its production ?
What Decreases SULT1A1 / Blocks Sulfonation
PAPS Depletion (3'-Phosphoadenosine-5'-Phosphosulfate)Remember PAPS is the sulfate donor
No PAPS = no sulfonation regardless of enzyme levels
PAPS requires sulfur and ATP to synthesize
Low sulfur intake = limiting step
Direct inhibitors
Minoxidil itself at high doses can saturate and deplete PAPS
Using too much topical minoxidil = diminishing returns
Also many healthy polyphenols compete with or block sulfonation at liver but does little effect at hair follicle but it does
What Actually Supports SULT1A1 & Sulfonation
1. Sulfur Intake — Most ImportantPAPS synthesis requires inorganic sulfate. Your body gets sulfate from:
MSM (Methylsulfonylmethane) A supplement for this has a weak effect for human ig research has only been conducted to rats but weak research has been done on humans
NAC (N-Acetyl Cysteine) raises cysteine which is imp for PAPS synthesis this mechanism works but is indirect works best by combining with minoxidil
Taurine sulfur containing
Dietary sulfur foods eggs, meat there are some vegetables but seriously who eats them
MSM is the most direct and bioavailable sulfate source for PAPS synthesis. but low rsearch
2. Support things for SULT1A1 enzyme
SULT1A1 needs cofactors to function properly:
Magnesium : involved in PAPS synthesis
B vitamins (especially B2/riboflavin) : sulfur metabolism
Selenium : supports sulfur enzyme activity generally
Zinc : general enzyme cofactor
but low potency for working with minoxidil
3. Thyroid Function
important
Thyroid hormones upregulate SULT1A1 expression
Hypothyroidism is associated with poor sulfonation
if you're a poor minoxidil responder you might have bad thyroid
Tips : have good thyroid plus dont consume soylent food supplement MSM and NAC and will talk about its potency in next thread and avoid these polyphenols 2 to 3 hrs around application although the research is mostly done around SULT1A1 in liver cell for polyphenols and has a little effect on hair but has a effect .
Now ill be taking about MSM( Methyl Sulfonate methane )
MSM is a sulfur compound found in primitive plants ,animal and humans it also can be chemically made but the quantity is low in plants and animal and other foods
PHYSICAL PROPERTIES
Colourless, Odorless and white crystalline solid
MAIN USE
Commonly used for joint health supplement and is a anti inflammatory drug
SIDE EFFECTS
Mild gastrointestinal pain, headaches, insomnia, or skin rashes. not extreme tho
WORKING MECHANISM
Methylsulfonylmethane (MSM) works primarily by modulating the body's response to inflammation and oxidative stress at the cellular and genetic levels It acts as an adaptable regulator rather than a direct blocker, influencing several key biological pathways simultaneously
HOW THIS WORK FOR HAIR ?
1.SULFUR DONATION
MSMis a bioavailable sulfur it can provide bioavailable sulfur for SULT1A1 enzyme activity
2. ENHANCED PENETRATION
MSM increases cell membrane permeability when used with minoxidil it will penetrate deeper into skin works via ion and membrane modulation
Take this drug more than 3g a day to work but not fix for working with minoxidil due to
Low research for human hair but we have mechanism
FDA approved drug
NEXT NAC ( N-acetylcysteine )
WORKING MECHANISM
1.OXIDATIVE STRESS REDUCTION
Spoiler
It neutralizes free radicals and reactive oxygen species (ROS) that can damage hair follicles and trigger premature transition to the shedding phase.
2.GLUTATHOINE SYNTHESIS
By providing cysteine NAC helps maintain high levels of glutathione in the follicle, which is essential for protecting the rapidly dividing cells in the hair bulb
3.Inhibiting Hair-Loss Signals
NAC can suppress certain inflammatory mediators like PGD2 and TGF-β, which are known to inhibit hair growth in conditions like androgenetic alopecia (AGA)
Side Effects
While generally well tolerated, high intake can cause gastrointestinal issues such as nausea, vomiting, or diarrhea
Can work with minoxidil really well no fixed dosages for hair while some common dosages is 600 to 1200 mg told by some physicians
TBH these can be potent but has low roi and now will be taking about some other ways to max the usages
1. MICRO NEEDLING : We all know use it 3 times a week for 2 min at a part
2. USING TOPICAL TRETINOIN
Tretinoin upregulates the sulfotransferase enzyme. This can convert non-responders into responders
Apply a thin layer of tretinoin (0.01% to 0.025%) to thinning areas before minoxidil use it 3 to 4 times per week
