The Science of Healthy Hair, Hair Loss and How to Regrow Hair

Hair Biology and Psychology

• Hair is fascinating from a cellular biology and stem cell perspective 
  • Every individual strand of hair has its own stem cell niche
  • Hair growth duration varies depending on the hair and its location on the body

• Hair loss can cause anxiety and stress

  • Psychological well-​​being can impact hair coloration and growth rates
  • Hair thinning or loss can lead to anxiety or depression for some people
    Hair Loss and Hair Growth

• Hair loss affects 50% of men and women by age 50

  • Causes anxiety, leading to attempts to halt or reverse hair loss
• Hair loss occurs gradually from age 30 to 50
• Psychological states can impact hair growth/​​loss and vice versa

Biology of Hair and Stem Cells

• Hair growth relies on endogenous stem cells (cells within the body)
• Hair consists of a root (below the skin) and a shaft (above the skin)
• Hair bulb: a small pocket at the base of the root containing stem cells 
  • Stem cells divide and give rise to daughter cells, which become various types of cells that make up the hair
• Hair is made up of a protein called keratin
• Melanin-​​producing cells give hair its pigment

Sebaceous Glands and Sebum

• Sebaceous glands are located next to hair roots within the dermal layer of the skin
• Produce sebum, an oily substance that: 
  • Forms a seal where the hair exits the skin, providing waterproofing
  • Helps maintain skin health and hair growth

Mechanical and Chemical Approaches to Hair Loss

• Mechanical approaches: massaging the scalp, micro-needling

• Chemical approaches: targeting hormones such as estrogen, thyroid hormone, insulin-​​like growth factor, and androgens (e.g., testosterone, dihydrotestosterone) that regulate hair growth and stem cell populations
  Sebum and Hair Growth

• Sebum: essential for waterproofing and immune system function

  • Strong antibacterial and antimicrobial properties
  • Protects hair root and surrounding region from infection
• Relevant to psoriasis and fungal components causing hair loss

Erector Pili Muscle

• Lies diagonally between hair bulb and skin surface
• Contracts when cold or scared, causing goosebumps 
  • Pulls skin down around hair follicles
  • Hairs stand up, trapping air for warmth (more effective in hairier individuals)
• Important for huskies and other animals in cold environments

Hair Growth Process

• Hair grows from the bottom up, starting deep within the root
• Three phases of hair growth: 
  1. Anagen (growth) phase 
     • Duration varies depending on body region
     • Scalp hair: 2–8 years (average 6 years)
     • Eyebrow hair: 4.2 months (average)
  2. Catagen (transition) phase
  3. Telogen (resting) phase

Factors Affecting Hair Growth

• Duration of anagen phase differs between individuals 
  • Longer anagen phase = longer hair growth period
• Rate of hair growth likely similar within a given body region 
  • Differences in hair length more likely due to anagen phase duration

• Increasing blood flow to hair stem cells and melanocytes can slow hair loss and extend hair growth duration

  • Methods: scalp massage, avoiding tight hats, using peppermint oil or menthol-​​type oils
  • Best used in conjunction with other hair growth treatments
    Hair Growth Phases and Factors

• Three critical stages of hair life cycle:

  • Anagen phase: hair growth
  • Catagen phase: hair receding and dying
  • Telogen phase: rest period, no new hair proteins added 
    • Hair can reenter the life cycle and grow again if conditions are right
• Hormones act as accelerators and brakes on these phases

Minoxidil and Hair Growth

• Minoxidil (Rogaine) was originally a hypertension drug 
  • Lowers blood pressure by causing vasodilation
  • Increases blood flow to hair follicles, extending the anagen phase
  • Can slow hair loss on the scalp and other areas of the body
• Side effects of minoxidil: 
  • Lowered blood pressure
  • Swelling of ankles
  • Headaches
  • Dizziness

Minoxidil and Prolactin

• Minoxidil can increase the hormone prolactin 
  • Prolactin is antagonistic to dopamine, which is associated with motivation and drive
• Side effects of increased prolactin: 
  • Reduction in libido
  • Reduction in overall feelings of well-being
  • Apathy
  • Gynecomastia (male breast tissue growth)
  • Milk letdown in extreme cases

• Women who take minoxidil can experience similar side effects as men
  Minoxidil for Hair Loss

• Mainly used to slow hair loss, not reverse it

• Dosage is crucial 
  • Oral minoxidil: ranges from 0.25 mg to 5 mg per day
  • Topical minoxidil: typically 5% concentration, used once or twice daily
• Minoxidil works by increasing blood flow to the hair stem cell niche 
  • Oral minoxidil: wide dosage range, from 0.25 mg to 5 mg per day
  • Topical minoxidil: typically 5% solution, used once or twice daily
  • Leave solution on the scalp for 3–5 minutes for absorption

Other Treatments for Hair Loss

• Low-​​dose Tadalafil (2.5–5 mg) 
  • Increases blood flow to the scalp, similar to minoxidil
• Platelet-​​rich plasma (PRP)
  • Controversial treatment, involves injecting platelets into the scalp
  • Expensive and results may be temporary
  • Not sufficient clinical data to support its use

• Microneedling

  • Mechanical stimulation of the hair follicle and stem cell niche
    Microneedling for Hair Growth

• Microneedling involves using small needles to create micro-​​injuries in the skin

  • Stimulates hair growth by reactivating stem cells in the hair follicles
  • Can be used in combination with other hair growth treatments for better results
• Microneedling can cause some pain and bleeding, but is generally well-tolerated 
  • Needle lengths of about 1mm seem to be more effective than shorter lengths
• Combination of microneedling and minoxidil treatment is more effective than either treatment alone 
  • Can even recover “dead zones” on the scalp where hair no longer grows
  • However, minoxidil treatment may need to be continued indefinitely to maintain results

Botox for Hair Growth

• Botox (Botulinum neurotoxin) is a bacterial toxin that inhibits nerve cell communication 
  • Commonly used to reduce wrinkles by paralyzing facial muscles

• Botox injections can be applied to the scalp to relieve tension

  • May improve blood flow and stimulate hair growth
    Botox for Hair Loss

• Botox treatment becoming common for scalp

  • Decreases tensile nature of scalp skin, allowing more blood flow to hair follicles
• Requires skilled practitioner to avoid cosmetic issues
• Botox wears off, needs repeated injections
• Efficacy for hair loss not yet clear, needs more clinical studies
• Alternative: low dose tadalafil for increased blood flow without side effects

Cutis Verticis Gyrata

• More common in men, but occurs in women too
• Lumping of skin on scalp, associated with pattern hair loss
• Botox injections can help flatten folds and improve hair growth

Chemical Variables in Hair Growth

• IGF‑1 (Insulin Growth Factor 1) and Cyclic AMP: accelerators of hair growth 
  • Extend the anagen (growth) phase
• PDE (Phosphodiesterase) and TGF-​​beta 2: brakes on hair growth 
  • Shorten the anagen phase or extend the catagen (receding) or telogen (quiescent) phases

Androgen-​​Related Alopecia

• Testosterone and its derivatives (e.g., dihydrotestosterone or DHT) inhibit IGF‑1 and Cyclic AMP
• Higher testosterone levels in younger individuals, but more conversion to DHT with age
• DHT binds to androgen receptors, inhibiting hair growth
• Pattern of androgen receptors on scalp is inherited, affecting hair loss patterns

• Androgen receptors on face responsible for beard growth, which can increase with age and DHT levels
  Androgen Receptors and Hair Growth

• Androgen receptors differ between scalp, face, and back

  • High density of androgen receptors on the back leads to hair growth
  • High density of androgen receptors on the scalp can lead to hair loss
• Treatments for hair loss often focus on inhibiting DHT or the conversion of testosterone to DHT

Chemically Adjusting Hair Growth Pathway

• Caffeine can stimulate hair growth and halt hair loss 
  • Potent Pde inhibitor, indirectly stimulates IGF One
  • Can be applied topically in ointments or creams
  • Comparable efficacy to minoxidil without side effects
  • Not a replacement for minoxidil, but a good alternative
• Increasing IGF One can also promote hair growth 
  • Prescription drugs like growth hormone and Cermorellin can increase IGF One
  • Comes with potential side effects and risks, including increased cancer risk

• Insulin sensitivity is important for IGF One activity

  • Avoid insulin resistance and obesity to prevent hair loss
  • Supplements like Myoinostatol, Berberine, and Metformin can improve insulin sensitivity
  • Regular exercise and a healthy diet are crucial for maintaining insulin sensitivity and hair health
    Metformin and Berberine

• Equally effective in reducing blood sugar levels

• Can improve insulin sensitivity
• Should be taken with carbohydrates to avoid discomfort

Iron and Hair Growth

• Iron and ferritin play a key role in cell growth pathways for hair
• Blood levels of iron should be measured before supplementing 
  • Women: 25–100
  • Men: 30–150
• Iron can be obtained through nutrition and supplementation

Dihydrotestosterone (DHT) and Hair Loss

• DHT shortens the growth phase of hair and miniaturizes hair follicles
• Reducing DHT can help maintain hair growth and prevent hair loss

Saw Palmetto

• Weakly inhibits 5‑alpha reductase, reducing DHT
• Low side effects, low cost, and available over the counter
• Typically taken at 300mg per day, divided into 2–3 doses

Herbal Compounds and Hair Growth

• Difficult to study due to multiple variables and combinations
• Some may have minor effects on hair growth, but clinical studies are lacking
• Curcumin may inhibit 5‑alpha reductase and DHT, but can have side effects

Ketoconazole

• Antifungal initially developed to treat dandruff and psoriasis
• Can increase hair number and diameter, but may cause dry, brittle hair
• Mechanism of action involves disrupting fungal growth and reducing DHT
• 80% response rate in maintaining hair when used 2–4 times per week with 3–5 minutes of scalp contact time

• Unclear if it can stimulate new hair growth
  Ketoconazole Shampoo for Hair Loss

• Ketoconazole shampoo can help with hair thinning and loss

  • Recommended usage: 2–4 times per week, 3–5 minutes of scalp contact
  • Massage into the scalp and around hair follicles
• Likely works by offsetting reductions in the hair growth phase and exacerbation of the hair shedding phase
• Important to use a shampoo with at least 2% concentration of Ketoconazole 
  • Many available options are 1% or lower
• Side effects are generally mild, affecting 1–8% of users 
  • Irritation of the scalp, thinning and brittleness of hair
  • Can be offset by using shampoos containing biotin

Finasteride for Hair Growth

• Finasteride inhibits five alpha reductase, reducing DHT and promoting hair growth 
  • Can increase hair count by 20% and hair thickness by 20–30%
  • Reduces hair loss in 90% of users
• Side effects can be significant if not dosed properly 
  • Sexual side effects, reduced motivation, and depressive symptoms
• Comes in oral and topical forms 
  • Topical form was developed to reduce systemic side effects
  • However, topical form can still enter systemic circulation
• Dosing is crucial for minimizing side effects 
  • Start with the lowest effective dose (0.1–0.2 mg orally)
  • Topical finasteride dosing is harder to control, but 1% solution is thought to be equivalent to 1 mg systemic finasteride

• Patience is key, as hair growth may not be noticeable for the first few months of treatment
  Finasteride and Dosage Recommendations

• Finasteride sensitivity varies among individuals

• Recommended starting dosage: 0.5 to 1 mg per day 
  • Some may need to reduce dosage or stop taking it due to side effects
• Results take time; increasing dosage too quickly is not advised
• Long-​​term commitment needed; start with a low dose for an extended period (e.g., 25 weeks) before considering increasing dosage

Topical Finasteride

• Associated with 30% to 50% fewer or less severe side effects than oral finasteride
• Recommended starting dosage: 1 ml of 0.25% solution, taken once per week
• Monitor DHT levels and work with a doctor

Post-​​Finasteride Syndrome

• Occurs after stopping finasteride use
• Symptoms include reduced libido, erectile dysfunction, and depression
• More common in younger males (20s and 30s) than older males
• DHT likely plays a role in brain development and maturation, which may be affected by finasteride use

Dutasteride

• Inhibits all three isoforms of the 5‑alpha reductase enzyme
• Works 2 to 5 times faster than finasteride for hair regrowth
• Reduces DHT by 95%
• Typical dosage: 0.5 to 2.5 mg taken orally
• Associated with significant side effects, including reduced sex drive, increased estrogen and prolactin levels, and gynecomastia

• Some people choose Dutasteride for faster results, despite the side effects
  Mild Inhibition of DHT Pathway for Hair Growth

• Topical caffeine, salt palmetto, and ketoconazole can mildly reduce DHT

• Finasteride is a potent stimulus for increasing hair growth
• Combination treatments involving mechanical and chemical stimuli are most effective 
  • Microneedling and finasteride can lead to significant hair regrowth
  • Can also use ketoconazole shampoo and salt palmetto

Individual Response to Hair Growth Treatments

• People have highly individual responses and side effect profiles to treatments
• Start with minimal effective dosages and consult a medical professional
• Consider both mechanical approaches (e.g., massage, microneedling) and chemical pathways (e.g., sal palmetto, ketoconazole shampoo)

Evaluating Hair Growth Treatments

• Understand the biology of hair growth and the mechanisms of various treatments
• Place treatments into categories based on their known or potential mechanisms
• Evaluate which treatments might be right for you