Half of men experience some degree of hair loss by the time they turn 50 and 40% of women are affected by age 70. “Pattern” hair loss is the most common cause of hair loss in both men and women.

Two medications are available to treat pattern hair loss: minoxidil (Rogaine) for men and women and finasteride (Propecia) for men. Unfortunately, neither of these medications is very effective, and both have side effects.

A number of integrative interventions including solubilized keratin, essential fatty acids, and saw palmetto extract may prevent hair loss and promote healthy hair growth.

Causes

• Hereditary and genetic factors: Influences age of onset, rate, and degree of hair loss
• Hormonal: Includes pregnancy, menopause, and hormonal disorders such as polycystic ovary syndrome and thyroid abnormalities
• Medical: Includes autoimmune diseases, skin conditions, and severe physical or emotional trauma
• Drug-induced: Includes chemotherapy and radiation therapy, beta-blockers, and oral contraceptives
• Nutritional: Severe protein and essential fatty acid deficiencies; overall malnutrition and crash diets; and iron, zinc, biotin, and vitamin D deficiencies

Treatment

• Finasteride, an oral medication approved for men, is a 5α-reductase inhibitor that suppresses the conversion of testosterone to dihydrotestosterone (DHT), which contributes to male pattern hair loss.
• Topical minoxidil is a vasodilator approved in both 2% and 5% formulations for treatment of pattern hair loss in men and women.
• Surgical hair restoration in the form of hair transplantation is widely used to treat pattern hair loss in men and women.
• Scalp cooling is an effective method of preventing hair loss induced by chemotherapy, reducing the risk by 62%.

Novel and Emerging Strategies

• While dutasteride, a medication like finasteride, has not been FDA approved as a treatment for hair loss, evidence indicates it effectively improves scalp hair growth, possibly even more than finasteride.
• Topical estrogens are available in Europe for use in hair disorders. In a trial in 53 women with female pattern hair loss, volunteers applied a topical 0.025% 17α-estradiol solution to their scalps daily for eight months. The treatment led to improvements in hair density, and was well tolerated during the study period.
• Early research indicates topical caffeine may exert positive effects on hair growth, including a stimulatory effect on hair follicles.

Integrative Interventions

• Solubilized keratin: In a placebo-controlled study in women with stressed or damaged hair, there was less hair loss, improved hair strength, and better hair appearance in the group taking Cynatine, a novel form of solubilized keratin.
• Essential fatty acids: A trial in women with early-stage hair loss found daily supplementation with fish oil, black currant seed oil (providing gamma-linolenic acid), lycopene, and vitamins C and E led to improved hair density compared with a control group.
• Silicon: In a study of women with fine hair who received orthosilicic acid (which provides silicon) or placebo for nine months, hair strength and elasticity were better preserved and hair thickness increased in the supplemented group.
• Saw palmetto: In a two-year trial comparing the effects of oral saw palmetto extract to finasteride in 100 men with mild-to-moderate pattern balding, finasteride led to hair regrowth in 68% of subjects, while 38% of those in the saw palmetto group experienced improved hair growth.
• Tocotrienols: In a study involving 38 women and men with various types and degrees of hair loss, those receiving supplements with alpha-tocopherol plus mixed tocotrienols experienced a more than 34% increase in hair numbers over eight months, while those receiving placebo experienced a slight decrease in hair numbers.

Half of men experience some degree of hair loss by the time they turn 50. Forty percent of women are affected by age 70 (Stough 2005; Levy 2013; Qi 2014; Hawit 2008).

“Pattern” hair loss is the most common cause of hair loss in both genders. In genetically susceptible individuals, the male hormone dihydrotestosterone, or DHT, contributes to pattern hair loss (Qi 2014; Santos 2015; Mayo Clinic 2015). An autoimmune condition called alopecia areata is another relatively common cause of hair loss, affecting about 2% of people at some point during their lives (Stough 2005; Levy 2013; Qi 2014; Hawit 2008). Other less common causes of hair loss include some medications, severe trauma or stress, and nutritional deficiencies.

Two medications are available to treat pattern hair loss: minoxidil (Rogaine) for men and women as an over-the-counter topical treatment, and finasteride (Propecia), an oral prescription drug for men that blocks the conversion of testosterone to DHT. Unfortunately, neither of these medications is remarkably effective, and both have side effects (Mayo Clinic 2015; Levy 2013).

Surgical hair restoration is an effective but expensive and invasive option for both men and women with long-term hair loss (Levy 2013; Stough 2005). For people undergoing chemotherapy—one of the most common medical causes of hair loss—scalp cooling can help maintain hair density (Shin 2015).

Intriguing new scientific findings are uncovering the next generation of therapies to combat hair loss. For instance, several trials have found that injecting platelet-rich plasma into the scalp can safely increase hair density (Ferneini 2016; Singh 2016). And the recent discovery that stem cells in hair follicles regulate hair growth has led to new avenues of research that may yield more promising treatments (Santos 2015).

In addition to a healthy diet (Lin 2016), a number of integrative interventions, including solubilized keratin (Beer 2014), essential fatty acids (Le Floc'h 2015), zinc (Karashima 2012), and saw palmetto extract (Murugusundram 2009; Rossi 2012) may prevent hair loss and promote healthy hair growth.

In this protocol, you will learn about different types of hair loss and their causes. Conventional as well as novel and emerging treatment strategies will be reviewed, and several integrative interventions that may help promote healthy hair growth will be examined.

An average person’s scalp contains 250,000‒500,000 hair follicles. Each follicle undergoes repeated cycles of three phases (Santos 2015):

• anagen, the growth phase, during which hair elongates;
• catagen, the regression phase, during which the follicle shrinks and detaches from its hair; and
• telogen, the resting phase.

On a healthy scalp, about 90–95% of hair follicles are in the anagen phase at any given time (Qi 2014; Santos 2015). Under normal circumstances, scalp hair shedding of 50‒150 hairs per day is matched by new hair growth at the same rate, so there is no net loss or gain (Fiuraskova 2003; Ahanogbe 2015).

Cells at the base of the hair follicle, in a region called the dermal papilla, are responsible for initiating and regulating the hair follicle cycle (Driskell 2011). These dermal papilla cells are regulated by hormones, growth factors, and inflammatory cytokines (Santos 2015; Inui 2013).

Types of Hair Loss

Androgenetic alopecia, also called male and female “pattern” hair loss, is the most common type of alopecia in men and women. Male pattern hair loss typically causes thinning and recession along the front hairline and temples, as well as the crown of the head. Female pattern hair loss usually causes thinning at the crown of the head (Qi 2014).

Male pattern hair loss is triggered mainly by the effects of the androgen (male hormone) dihydrotestosterone (DHT) on the dermal papilla cells of the hair follicle. DHT is made from testosterone by the enzyme 5-alpha reductase. DHT shortens the anagen phase in genetically predisposed hair follicles, resulting in smaller and shorter hairs (Fiuraskova 2003; Qi 2014). Female pattern baldness may involve a follicular sensitivity to DHT (Herskovitz 2013); however, the drop in estrogen after menopause may also contribute to changes in hair follicles that result in increased hair loss (Levy 2013).

Other types of alopecia include (Qi 2014; Hawit 2008; Mayo Clinic 2015):

• Alopecia areata. Alopecia areata, an autoimmune condition in which the immune system attacks hair follicles, can affect children and adults of both genders. It causes round patches of balding, mostly on the scalp and beard region.
• Telogen effluvium. Telogen effluvium is a condition in which 20–50% of scalp hair follicles abnormally transition into the telogen (resting) phase and shed their hair. Telogen effluvium is often triggered by physical or psychological stress, or illness. More women than men have telogen effluvium.
• Anagen effluvium. Anagen effluvium is a condition in which the shafts of hairs in the anagen (growth) phase are weakened and break. It is most commonly triggered by radiation therapy and cancer chemotherapy, but may also be related to heavy metal toxicity or exposure to other poisons (Harrison 2009).
• Cicatricial (scarring) alopecias. Hair loss that involves scarring is usually related to an underlying condition or disease. Chronic pressure to the scalp from certain hairstyles can result in traction alopecia, while application of chemicals can also cause long-term inflammation and scarring. Unlike other types of hair loss, cicatricial alopecias are often permanent.

Medical Conditions Associated with Hair Loss

Cardiovascular disease and metabolic syndrome. Androgenetic alopecia may be an indicator of cardiovascular risk. In one study, 80 men and 70 women with early-onset androgenetic alopecia had significantly higher triglyceride as well as total and LDL-cholesterol levels, and lower HDL cholesterol, than men and women without hair loss (Arias-Santiago 2010). In another study, male androgenetic alopecia was correlated with high blood pressure (Ahouansou 2007).

Early onset of pattern hair loss may be a stronger predictor of cardiovascular disease than later-onset androgenetic alopecia. In one study, men with early-onset androgenetic alopecia were more than three times as likely to need coronary artery bypass surgery before age 60 than men with later-onset hair loss and those without hair loss (Matilainen 2001). In addition, early-onset androgenetic hair loss has been linked to an increased risk of metabolic syndrome in men (Banger 2015; Gopinath 2016), while female pattern hair loss has been associated with metabolic syndrome in women (Herskovitz 2013).

Prostate conditions. Research has not consistently found a connection between androgenetic alopecia and benign prostate enlargement, even though both are related to high levels of DHT (Arias-Santiago 2012; Dastgheib 2015; Qi 2014; Carson 2003). However, a review of studies concluded male pattern hair loss occurring at the crown of the head was associated with a 25% increase in prostate cancer risk (Amoretti 2013). Additional evidence found a 56% increase in prostate cancer deaths in men with any balding and an 83% increase in men with moderate balding, pointing to a relationship between male pattern hair loss and fatal prostate cancer (Zhou 2016). Further evidence for this connection is found in research showing that use of finasteride, a 5-alpha reductase inhibitor that reduces serum DHT levels, is associated with reduced overall prostate cancer risk (Wilt 2008; Chau 2015); although it may be less effective at preventing high-grade than low-grade prostate cancers (Hoque 2015).

Because some evidence suggest androgenetic alopecia may correlate with increased prostate cancer risk, men experiencing male pattern hair loss, especially those whose hair loss began at an early age, should monitor their prostate health and take steps to prevent prostate cancer. More information about keeping your prostate healthy is available in the Prostate Cancer Prevention protocol.

Risk of hair loss increases with age and is higher in those with a family history of hair loss (Mayo Clinic 2015). While men have higher rates of androgenetic alopecia, women have a higher risk of telogen effluvium (Qi 2014).

Causes of Hair Loss

Causes of hair loss generally fall into five categories: hereditary, hormonal, medical, drug-related, and nutritional:

• Hereditary causes. Heredity is an important influence on age of onset, rate, and degree of hair loss (Mayo Clinic 2015).
• Hormonal causes. Hair loss is more common at times of hormonal changes such as during pregnancy, after childbirth, and with menopause. Even the onset of puberty can mark the beginning of hair loss in some men (Mayo Clinic 2015). Other hormonal causes of hair loss include polycystic ovary syndrome (PCOS), hyperthyroidism and hypothyroidism (Mayo Clinic 2015; Goodman 2015; Levy 2013).
• Polycystic ovary syndrome. Polycystic ovary syndrome (PCOS), which affects about 5–10% of women, can lead to female pattern hair loss (Herskovitz 2013; Quinn 2014; Madnani 2013).
• Thyroid abnormalities. Both hyper- and hypothyroidism, as well as autoimmune thyroid disease with normal levels of thyroid hormone, are associated with alopecia areata (Lyakhovitsky 2015; Branisteanu 2014).
• Medical causes. Several medical conditions can cause hair loss:
• Some autoimmune diseases (Chen, Wang, Lin 2016)
• Tinea capitis, a fungal infection of the scalp (Ahanogbe 2015), psoriasis, seborrhea, and allergic contact dermatitis (Harrison 2009; Mubki 2014a)
• Trichotillomania (a psychological disorder characterized by hair pulling) (Ahanogbe 2015)
• Liver or kidney failure (Harrison 2009)
• Inflammatory bowel disease (Harrison 2009)
• Chronic infections such as HIV (Harrison 2009)
• Severe physical or emotional trauma (Harrison 2009; Ahanogbe 2015)
• Heavy metal poisoning (Harrison 2009)
• Drug causes. Most drug-induced hair loss is reversible, and is generally due to telogen effluvium or anagen effluvium (Piraccini 2006; Tosti 2007). Many different medications have caused cases of hair loss, with only a few regularly causing this side effect. Cancer chemotherapy drugs, on the other hand, cause hair loss in most people who take them (Santos 2015; Llau 1995). Radiation therapy is another potential cause of hair loss in cancer patients (Qi 2014). General anesthesia during surgery has been associated with telogen effluvium (Desai 1984), although general stress associated with surgery may contribute as well. Some other drug categories that may cause hair loss include (Llau 1995; Mubki 2014a):
• Anticoagulants
• Beta-blockers
• Oral contraceptives
• Anti-thyroid medications
• Anti-seizure medications
• Retinoids
• Amphetamines
• Mood stabilizers
• Antidepressants
• Antimicrobial and antiviral medications
• Nutritional causes. Severe protein and essential fatty acid deficiencies; overall malnutrition and crash diets; and iron, zinc, biotin, and vitamin D deficiencies can cause hair loss (Harrison 2009; Mubki 2014a).

Other contributing factors. Unhealthy scalp and hair care practices can contribute to hair loss. The following practices may help prevent unnecessary hair damage and loss (Mayo Clinic 2015; AAD 2017):

• Avoid tight hairstyles that put pressure on the scalp, such as tight braids, buns, and ponytails.
• Avoid twisting, rubbing, and pulling on hair, and comb hair gently with a wide-toothed comb.
• Avoid harsh hair treatments like hot rollers, curling irons, hot oil treatments, and permanents.

Androgenetic Alopecia Treatment

Two drugs, finasteride and minoxidil, are approved by the Food and Drug Administration (FDA) for the treatment of hair loss in men. Finasteride is an oral medication that inhibits 5-alpha reductase and blocks the conversion of testosterone to DHT (AHLA 2010; Qi 2014). Minoxidil lengthens the anagen phase, shortens the telogen phase, increases the growth rate, and increases the size of hair follicles. Minoxidil can be considered in men who do not respond adequately to finasteride treatment, or as an add-on to other treatments. Topical minoxidil is FDA approved in both 2% and 5% formulations for treatment of pattern hair loss in men and women (Ahanogbe 2015; Stough 2005).

These medications are only effective during active use, so they must be used continuously and indefinitely (Qi 2014; Levy 2013). In addition, they may cause unwanted side effects. Minoxidil may cause itching and irritation of the scalp, as well as excessive facial hair growth in women (Levy 2013). Finasteride may cause sexual dysfunction in some men (Ahanogbe 2015).

Alopecia Areata Treatment

For many people with alopecia areata, the condition is primarily a cosmetic concern (Messenger 2021). However, hair is an important aspect of a self-image and hair loss can be deeply emotionally and psychologically distressing for some people with alopecia areata (Messenger 2021; NAAF 2022a). Thus, psychosocial support is a central component of management.

There is no curative treatment for alopecia areata, and evidence for the effectiveness of existing treatments is limited (Messenger 2021). However, a promising step forward occurred in June 2022 when the FDA approved the first systemic treatment for alopecia areata—the Janus kinase (JAK) inhibitor baricitinib (Olumiant).

Psychological support. Psychosocial support is a primary component of the management of alopecia areata, due to the emotionally distressing nature of the condition itself as well as the uncertainty of its course and treatment (Messenger 2021; NAAF 2022a).

Although a physician or other health care provider may be chiefly responsible for guiding the patient through the challenge of managing the emotions attendant to hair loss, other resources can be vital. Professional counseling can be helpful, as can patient support groups. The National Alopecia Areata Foundation has a variety of resources available to help patients (Messenger 2021; NAAF 2022a).

Local and topical therapies:

• Corticosteroids. For people who opt for treatment, superficial injection or topical application of corticosteroids is a first-line therapy when there is patchy hair loss or less than 50% of the scalp is involved. People with less than 25% scalp involvement may be the best candidates for this treatment, due to the large number of injections necessary to treat a larger area. There are no randomized controlled trials of this therapy for alopecia areata (Messenger 2021; Majid 2012). Side effects of corticosteroid injections are generally minor (NAAF 2022b).
  
  Potent topical corticosteroid application is also sometimes used in cases of partial scalp involvement, particularly in populations such as children who may not tolerate intralesional injections. Evidence for effectiveness of this approach is limited (Messenger 2021; Majid 2012).
• Immunotherapy. In patients with extensive hair loss, topical immunotherapy has been a common treatment. This therapy involves the use of irritant chemicals (diphenylcyclopropenone or squaric acid dibutyl ester) that induce contact dermatitis, which is theorized to then modulate immune response (Messenger 2021; Majid 2012; Mahasaksiri 2021). Randomized trials have not been conducted for this treatment for alopecia areata, and the response rate in uncontrolled trials has been uneven (Messenger 2021). Local side effects are common (NAAF 2022b).
• Anthralin. Topical anthralin, a synthetic, tarry psoriasis medication, is an irritant agent. It is considered a second-line treatment for alopecia areata (NAAF 2022b; Hon 2022). Topical anthralin is believed to work through modulating immune response (Majid 2012). It appears to be less effective than intralesional steroids or topical immunotherapy, and the evidence base for its use is anecdotal. Side effects result from the topical irritant nature of this treatment and include redness and scaling. Anthralin stains skin, clothing, and hair brown (Messenger 2021).

Systemic therapies:

• JAK inhibitors. In June 2022 the FDA approved baricitinib, the first systemic drug for severe alopecia areata (FDA 2022). It is an oral medication that inhibits Janus kinases (JAK) 1 and 2. JAK enzymes are involved in signaling pathways related to inflammation. Baricitinib has been approved since 2018 for the treatment of some people with rheumatoid arthritis. Various JAK inhibitors are in use for a range of inflammatory, autoimmune, and blood disorders, including other types of arthritis and ulcerative colitis (European Medicine Agency 2022). They include ruxolitinib (Jakafi), tofacitinib (Xeljanz), and upadacitinib (Rinvoq) (Harrington 2020). Ruxolitinib and tofacitinib have been used in alopecia areata (Messenger 2021).
  
  The approval of baricitinib for alopecia areata was based on the results of two randomized controlled trials (King 2022). The 1,200 participants enrolled in these trials had at least 50% hair loss at baseline. They received either 2 or 4 mg of baricitinib or placebo. After 36 weeks, about one-third of individuals in the 4 mg groups had reached 80% scalp hair coverage; about one in five people in the 2 mg group achieved 80% scalp hair coverage. In the placebo groups, just 3–5% of participants achieved this same level of scalp hair coverage.
  
  Baricitinib can cause a range of adverse effects, including increased infections, acne, cholesterol elevation, serum creatine phosphokinase and liver enzyme elevation, and headaches, among others. Longer randomized controlled trials are necessary to clarify the safety and long-term effectiveness of baricitinib for alopecia areata (FDA 2022; King 2022).
• Systemic corticosteroids. Oral systemic corticosteroids are sometimes used to control active, severe disease. However, duration of use is limited by typical corticosteroid side effects, so this is considered a temporary measure (NAAF 2022b).
• Methotrexate. Observational studies indicate methotrexate (Trexall) may be effective for alopecia areata, particularly in adults and in combination with systemic corticosteroids. Rigorous controlled studies are needed to confirm the efficacy of methotrexate, which has a considerable adverse effect profile (Messenger 2021; Majid 2012).
• Azathioprine. Small uncontrolled studies suggest azathioprine (Azasan) may stimulate hair regrowth in some patients with moderate-to-severe alopecia areata, with some improvement potentially continuing after the cessation of treatment. Controlled studies are necessary to confirm azathioprine’s benefit in this condition (Messenger 2021).
• Sulfasalazine. Sulfasalazine (Azulfidine) is used to treat ulcerative colitis, rheumatoid arthritis, and other autoimmune disease. Its exact mechanism of action is not yet understood, though it is believed to be attributable at least in part to immune-suppressive and immune-modulating activity (Messenger 2021; Choi 2022).
  
  Uncontrolled studies of sulfasalazine in alopecia areata show a relatively low rate of response with a potentially substantial relapse rate. Sulfasalazine usage is associated with a range of side effects, and it is recommended that blood count and liver function tests be carefully monitored early in treatment (Messenger 2021).

Telogen Effluvium Treatment

Telogen effluvium is generally triggered by a major physical or psychological stressor; the stressor typically occurs two to four months before hair loss begins. Hair regrowth typically occurs within four to six months if the stressor is short-lived, but if repetitive or chronic, hair loss may continue and topical minoxidil may be suggested (Qi 2014; Harrison 2009; Ahanogbe 2015).

Anagen Effluvium Prevention

Anagen effluvium is usually caused by chemotherapy or radiation therapy and normal hair regrowth typically begins within three to six months of treatment discontinuation. Scalp cooling is an effective method of preventing hair loss in some cases of chemotherapy-induced alopecia, reducing the risk of this type of hair loss by 62% (Shin 2015; FDA 2015; Qi 2014; Nangia 2017). A scalp cooling procedure that applies a refrigerated cap 30 minutes before, during, and up to 90 minutes after chemotherapy treatment is believed to prevent hair loss by reducing the amount of chemotherapeutic drug reaching the hair follicle, and lowering the rate of biochemical activity within the hair follicles (Shin 2015; FDA 2015; Qi 2014).

Novel and Off-Label Medications

Several new medications for treating androgenetic alopecia are currently under investigation (Gupta 2016; Vano-Galvan 2017; Cranwell 2016):

• Dutasteride (Avodart). Dutasteride, like finasteride, is a 5-alpha reductase inhibitor used to treat benign prostate enlargement. While dutasteride has not been approved by the FDA as a treatment for hair loss, considerable evidence indicates it effectively improves scalp hair growth, possibly even more than finasteride, and is relatively well tolerated (Cranwell 2016; Shanshanwal 2017; Choi 2016; Chung 2016; Gold Standard 2014).
• Prostaglandin analogs. Two drugs in this family, latanoprost (Xalatan) and bimatoprost (Latisse), have been studied for their effect on hair loss. Bimatoprost is FDA approved to promote eyelash growth, and one controlled study found latanoprost increased hair density and encouraged pigmentation of scalp hair in men with androgenetic alopecia (Choi 2015; Blume-Peytavi 2012).
• Estrogens. Estrogens have anti-androgenic effects and may play a role in hair follicle growth cycles. Oral contraceptives that contain estrogens treat hair loss associated with polycystic ovarian syndrome, a condition in women associated with excessive levels of androgens. Topical estrogens are available for use in hair disorders in Europe (Goodman 2015; Levy 2013). In a trial in 53 women with female pattern hair loss, volunteers applied a topical 0.025% 17α-estradiol solution to their scalps daily for 8 months. The treatment led to improvements in hair density, and was well tolerated during the study period (Kim, Lee, Lee 2012).
• Topical retinoids. Vitamin A plays an important and complex role in hair follicle function, and both deficiency and excess can trigger hair loss (Holler 2013; Duncan 2013; Cheruvattath 2006). A topical solution made with tretinoin (all-trans retinoic acid, a form of vitamin A, also known as Retin-A) and minoxidil may improve minoxidil’s efficacy (Kwon, Pyo 2007). In one such study, 5% minoxidil plus 0.01% tretinoin once daily was as effective in promoting hair growth as 5% minoxidil twice daily in men with androgenetic alopecia (Shin 2007). Tretinoin was shown in one trial to promote hair regrowth more effectively when combined with minoxidil than when used alone (Bazzano 1986).

Several medications that are not FDA approved for hair loss may be used off label in some cases (Table 1).

Topical Caffeine

Early research indicates topical caffeine may exert positive effects on hair growth, including a stimulatory effect on hair follicles. In hair follicle samples from men and women with androgenetic alopecia, caffeine exerted hair growth-promoting and anagen phase-lengthening effects. Caffeine’s positive effect on hair may result from inhibition of 5-alpha reductase, the enzyme involved in converting testosterone to dihydrotestosterone. It may also enhance blood flow to hair follicles (Herman 2013; Fischer 2014; Fischer 2007). In a laboratory study, treatment of hair fibers with a topical caffeine preparation that also contained vitamins B3 and B5, dimethicone, and an acrylate chemical led to growth of stronger hairs with wider shaft diameters (Davis 2011). In another study, caffeine blocked the inhibitory effect of testosterone on growth of hair follicles taken from scalp biopsies of men with androgenetic alopecia (Eicheler 1998).

Platelet-Rich Plasma Injections

Plasma—the fluid in which blood cells are suspended—contains proteins, glucose, electrolytes, and other compounds (URMC 2017). Plasma enriched with platelets, called platelet-rich plasma, is an abundant source of growth factors used successfully in several medical fields such as wound care, cosmetic surgery, and dermatology. Growth factors in platelet-rich plasma promote tissue regeneration and the growth of new blood vessels. Studies have shown platelet-rich plasma also prolongs the active growth (anagen) phase of the hair growth cycle (Ferneini 2016; Singh 2016).

In a randomized controlled trial, 25 participants with androgenetic alopecia received platelet-rich plasma injections on half of their scalp and placebo on the other half. Each participant received three treatments at one-month intervals. Six months after the first treatment, hair density increased on the platelet-rich plasma side of their scalps compared with placebo (Alves 2016). In a similar trial, 20 participants with pattern hair loss received platelet-rich plasma injections on half their scalp and placebo on the other. Each participant received three treatments at one-month intervals. After three treatment cycles, number of hairs in the target area and total hair density improved in areas treated with platelet-rich plasma versus control areas. No side effects were noted during treatment (Gentile 2015). Another clinical trial found platelet-rich plasma injections outperformed minoxidil (5%) in treating alopecia areata in 90 volunteers (El Taieb 2016).

New Medication Delivery

Iontophoresis is a technique in which a small electrical charge is applied to the skin to facilitate the penetration of molecules capable of being charged (ionizable) past the superficial layers of the skin. Iontophoretic delivery of minoxidil has increased drug accumulation in the hair follicle five-fold, and therefore has potential to increase the drug's effectiveness (Gelfuso 2013; Ashburn 1995). Microencapsulation, a technique in which a substance is coated with a delivery-enhancing chemical, has also increased minoxidil concentration in hair follicles. Combining microencapsulation with iontophoresis appears to have potential for improving uptake and possibly effectiveness of minoxidil, but this hypothesis awaits verification in clinical trials (Gelfuso 2015; Silva 2014).

B vitamins

Forty-six women with diffuse alopecia received 200 mg per day of oral vitamin B5 plus daily intramuscular injections of vitamin B6 for 20–30 days. The treatment was repeated after six months and resulted in improved hair condition and reduced hair loss (Brzezinska-Wcislo 2001). Results from animal studies demonstrated vitamin B6, in combination with the amino acid L-cystine, prevented hair loss caused by the chemotherapy drug doxorubicin (D'Agostini 2007; D'Agostini 2013).

Severe biotin (vitamin B7) deficiency can occur as the result of certain genetic mutations, causing hair loss as well as several other serious health problems (Zempleni 2008). In one study, 38% of women with self-reported hair loss exhibited biotin deficiency (Trueb 2016). In dogs, biotin supplementation may help improve hair growth (Frigg 1989), but human clinical trials have yet to verify this finding. Some preliminary evidence suggests that biotin supplementation may help treat alopecia caused by the medication valproic acid (Famenini 2014).

Vitamin D

A growing body of evidence shows that vitamin D participates in regulation of the hair cycle (Amor 2010; Malloy 2011; Vegesna 2002; Aoi 2012). In a case series of 210 women with female pattern hair loss, over 60% had below-normal vitamin D levels (Siah 2016). Low serum vitamin D levels are associated with autoimmune disorders including alopecia areata (Mahamid 2014; Aksu Cerman 2014). Telogen effluvium has been associated with vitamin D deficiency (Cheung 2016), and low vitamin D levels have been linked to greater hair loss in women with telogen effluvium and female pattern hair loss (Rasheed 2013).

In a 12-week trial, 48 patients with mild-to-moderate alopecia areata were treated twice daily with a topical solution containing calcipotriol, a synthetic form of vitamin D. At the end of the trial, more than 62% of participants had 75% or better hair regrowth, and 27% of participants had 100% hair regrowth (Cerman 2015). The case of a 7-year old boy with alopecia areata is also compelling: after failing to respond to topical minoxidil plus hydrocortisone, the boy experienced complete hair regrowth after three months of treatment with topical calcipotriol (Kim, Lee, Kim 2012). A study on 20 children with alopecia areata and 34 healthy controls found that vitamin D levels were inversely related to alopecia severity scores—as vitamin D levels went up, alopecia severity scores went down (Unal 2017).

Animal and preclinical models indicate topical vitamin D as well as calcipotriol may help prevent chemotherapy-induced alopecia, with some evidence suggesting this treatment can enhance hair regrowth (Jimenez 1992; Schilli 1998; Paus 1996; Wang 2006). In one study, topical vitamin D significantly reduced chemotherapy-induced hair loss in female mice (Chen 1998).

Saw Palmetto

Saw palmetto (Serenoa repens) is popularly used to treat prostate enlargement and androgenetic alopecia (Murugusundram 2009). A randomized controlled trial in 26 men aged 23‒64 with mild-to-moderate androgenetic alopecia found a combination of 200 mg saw palmetto extract, 50 mg beta-sitosterol, along with complementary amounts of lecithin, choline, inositol, niacin, and biotin was effective for measures of hair growth and quality. Self-assessment of satisfaction with hair growth and appearance, and investigative staff assessment of hair density both markedly improved (Prager 2002). An uncontrolled study in 50 men aged 20 to 50 years with androgenetic alopecia found a topical saw palmetto extract increased hair count (Wessagowit 2015). Another trial compared the effects of 320 mg oral saw palmetto extract daily to 1 mg finasteride daily in 100 men with mild-to-moderate androgenetic alopecia over two years. Finasteride led to hair regrowth in 68% of subjects, while 38% of those in the saw palmetto group experienced improved hair growth; treatment with saw palmetto was well tolerated (Rossi 2012). Researchers believe saw palmetto’s ability to inhibit 5-alpha reductase is at least partly responsible for its positive effects (Murugusundram 2009), and some have proposed that combining saw palmetto or beta-sitosterol with anti-inflammatory agents such as carnitine and alpha-lipoic acid may enhance its effectiveness (Chittur 2011; Chen, Wang, Mouser 2016).

Essential Fatty Acids

A trial in 120 women with early-stage hair loss found six months of daily supplementation with 460 mg fish oil, 460 mg black currant seed oil (providing gamma-linolenic acid [GLA]), 1 mg lycopene, and small amounts of vitamins E and C led to improved hair density compared with a control group. The supplemented group also had more anagen-phase hair and less telogen-phase hair compared with placebo (Le Floc'h 2015).

In a rodent study, most animals taking docosahexaenoic acid (DHA), an omega-3 fatty acid found mainly in fish oil, were protected from chemotherapy-induced alopecia (Takahata 1999). In another study of six rhesus monkeys with hair loss, daily treatment with omega-3 (72 mg) and omega-6 (26 mg) fatty acids was associated with decreased alopecia (Hamel 2017). Several studies have found attaching DHA to paclitaxel (Taxol), a commonly used chemotherapy drug, reduced the drug’s toxic side effects, including alopecia (Bradley 2001; Wolff 2003; Harries 2004).

Solubilized Keratin

Protein deficiency is a well-established cause of hair loss, and one protein, keratin, is the main component and primary structural element of hair. Age-related decline in keratin synthesis may lead to deterioration of the stability and flexibility of the hair shaft (Giesen 2011; Mubki 2014b). This could leave hair vulnerable to dryness and breakage with brushing and use of styling products and tools.

In one study, a supplement containing a novel form of solubilized keratin (Cynatine) plus vitamins and minerals was compared with placebo in 50 women who had signs of stressed or damaged hair. Cynatine contains a specially-processed, highly bioavailable peptide form of keratin, a rich source of cysteine. After 90 days, the Cynatine formula group had less hair loss; improved hair strength; improved anagen phase, telogen phase, and anagen:telogen ratio; and better hair appearance compared with placebo (Beer 2014).

Silicon

Silicon, a trace element present in the body in small quantities, is thought to function as a structural component of hair (Martin 2013). Silicon compounds are common in many edible plants (Jurkic 2013). Two studies have looked at the effect of supplementing with orthosilicic acid, which provides silicon, on hair health. In one study, 50 women were given 10 mg orthosilicic acid or placebo daily for 20 weeks. By the end of the study, hair brittleness decreased in women receiving the silicon supplement (Barel 2005). In the second study, 48 women with fine hair received the same compound or placebo for nine months; hair strength and elasticity were better preserved and hair thickness increased in the supplemented group compared with placebo (Wickett 2007).

Zinc

Zinc deficiency has been associated with hair loss (Saper 2009; Kil 2013). Zinc plays an important role in normal hair follicle activity, preventing follicle regression and enhancing follicle recovery (Kil 2013). Also, zinc may act as an anti-androgen and modulator of 5-alpha reductase (Gupta 2014).

Men and women with androgenetic alopecia, telogen effluvium, and alopecia areata have all been found to have lower serum zinc levels than people with no hair loss (Kil 2013). Early research suggests using supplements to correct zinc deficiency in people with related telogen effluvium can improve hair loss (Karashima 2012).

Lower zinc levels in patients with alopecia areata have been correlated with increased severity, longer duration, and higher likelihood of treatment resistance (Abdel Fattah 2016; Bhat 2009). In one uncontrolled clinical study, 15 subjects with alopecia areata and low zinc levels (≤ 70 mcg/dL) received 50 mg zinc gluconate per day. After 12 weeks, hair regrowth was seen in nine subjects and was correlated with improved zinc status (Park 2009). In addition, case reports suggest continued zinc gluconate supplementation may help maintain hair recovery after treatment of alopecia areata in those who respond to ultraviolet light therapy plus zinc (Lux-Battistelli 2015).

Tocotrienols

Tocotrienols—members of the vitamin E family—are naturally found in barley, wheat germ, and certain types of grains and nuts (Ahsan 2015). Similar to tocopherols, the more familiar form of vitamin E, there are four tocotrienols labeled alpha, beta, gamma, and delta (Ahsan 2015; Peh 2016). Tocotrienols are recognized to have important vitamin E activity, particularly with regard to their anti-inflammatory, cholesterol-lowering, and radioprotective properties (Peh 2016; Jiang 2014).

Emerging evidence suggest tocotrienols may help promote healthy hair. In a study involving 38 women and men with various types and degrees of hair loss, those receiving supplements with 23 IU alpha-tocopherol plus 50 mg mixed tocotrienols experienced > 34% increase in hair numbers over eight months, while those receiving placebo experienced a slight decrease in hair numbers (Beoy 2010).

Green Tea

There is evidence that green tea and its main polyphenol, epigallocatechin gallate (EGCG), may help prevent hair loss and aid in hair regrowth. In a mouse study, a topical EGCG solution protected against testosterone-induced hair loss (Kim 2011). In a study in mice with spontaneous hair loss, a green tea polyphenol solution added to drinking water promoted hair growth versus no growth with plain water (Esfandiari 2005). EGCG stimulated dermal papilla cells and promoted hair growth in human hair follicles in a laboratory setting as well as in human subjects (Kwon, Han 2007).

Selenium

Selenium intake is important for healthy hair follicle function, and selenium deficiency may play a role in hair loss (Sengupta 2010; Hwang 2011). In an eight-week randomized controlled trial in 64 women with polycystic ovary syndrome, 32 received 200 mcg supplemental selenium daily while the other half received placebo. At the end of the trial, the selenium group had a significant reduction in hair loss compared with placebo (Razavi 2016).

Topical Melatonin

Melatonin may be helpful as a topical treatment for hair loss. While not yet known how melatonin might combat alopecia, its ability to counteract oxidative stress, thought to play an important role in hair loss (Trueb 2009), and its ability to stimulate hair follicle growth (Fischer 2012) have been suggested.

In an early controlled trial, 40 women with female pattern hair loss or diffuse alopecia applied 1 mL of either a 0.1% topical melatonin solution or placebo solution to their heads nightly. After six months, the topical melatonin group had significantly more hair in anagen phase (Fischer 2004).

A set of four studies in men and women with early-stage androgenetic alopecia evaluated melatonin combined with other topical agents as a treatment for hair loss. In the first study, a 0.0033% melatonin solution, also containing biotin and a Ginkgo biloba extract, was applied nightly to the scalps of 30 men and women for 90 days. Both investigators and participants reported a decrease in severity of alopecia on day 30 and an even greater improvement on day 90. In the second study, 35 men used the same solution nightly for six months. Investigators noted an average 29% increase in hair number and density after three months and an almost 43% increase in number and 41% increase in density after six months, with more than 50% of participants responding to treatment. The third study used a hair count test, in which participants counted the number of hairs lost during 60 seconds of combing each morning, as the measure of response. Lost hair counts decreased over the 90-day trial in 20 female participants but not in 40 male participants using the melatonin solution. The final study included 901 men and 990 women who applied the solution nightly. Hair pull tests showed no hair loss in nearly 62% and new hair growth in nearly 23% of participants after 90 days of treatment. In addition, treatment with melatonin solution appeared to improve seborrhea (red, itchy, scaly skin) in participants with this condition of the scalp (Fischer 2012).

Iron

Iron deficiency can cause telogen effluvium (Grover 2013; Levy 2013; Malkud 2015). Low levels of ferritin, an iron-storing protein, have been observed in women with female pattern hair loss (Park 2013; Rasheed 2013), telogen effluvium (Moeinvaziri 2009; Rasheed 2013), and premenopausal hair loss (Deloche 2007). One study found lowest ferritin levels were associated with most severe hair loss. Assessment of iron status, and iron supplementation if necessary, can be considered in women with hair loss (Rasheed 2013).