Table 1.
Summary of clinical investigations on complementary and alternative treatments for alopecia
| Authors | Disease | Intervention | Control treatment | Patients, n | Quality ratingª | Study design | Efficacy | Safety |
|---|---|---|---|---|---|---|---|---|
| Natural Products | ||||||||
| Hertel et al. [9] 1989 | Diffuse alopecia | Oral L-cystine (70 mg), retinol, sss and gelatin | NA | 36 | 2 | Cohort study | Reduction of the telogen rate by 8.3%, increase of the anagen rate by 11%, and increase of the hair density by 6.9% | No AEs |
| Hertel et al. [9] 1989 | Diffuse alopecia | Oral L-cystine (70 mg), retinol, and gelatin | Placebo tablet | 47 | 1 | Double-blind RCT | Decrease in telogen rate by 13.5 vs. no change with placebo; 8% improvement in anagen rate vs. 7.8% decrease with placebo | No AEs |
| Morganti et al. [10] 1998 | AGA | Oral L-cystine, L-methionine, copper, zinc, soy oil, gelatin 4 times daily | Soy oil, starch placebo tablet | 24 | 2 | Cohort study | Significant mean change in total hair count after 50 weeks, 29 vs. 11% for placebo (p < 0.005) | No AEs |
| Gehring et al. [11] 2000 | AGA | Oral millet seed extract, L-cystine (2 mg) and calcium pantothenate twice daily (Priorin®) | Placebo tablet | 40 | 2 | Cohort study | Increased anagen rate (p = 0.0225) | No AEs |
| Lengg et al. [12] 2007 | TE | L-cystine, medicinal yeast, pantothenic acid, thiamine, keratin, para-aminobenzoic acid (Pantogar®) | Placebo capsule (lactose, microcrystalline cellulose and magnesium stearate) | 30 | 1 | Double-blind RCT | Significant improvement and normalization of the mean anagen hair rate after 6 months (p = 0.008) compared with placebo | GI symptoms (n = 4), weight gain (n = 4), transient elevation in pancreatic enzymes (n = 1) |
| Rushton et al. [13] 2002 | TE | L-lysine (1.5 g), iron, vitamin B12, vitamin C, biotin, selenium | NA | 22 | 2 | Cohort study | Significant reduction in hair shedding (39%, p < 0.001) | No AEs |
| Sisto et al. [18], 2012 | AGA | Caffeine shampoo | Placebo shampoo | 66 | 1 | Double-blind RCT | Greater improvement in intensity of hair loss, speed of progression of hair loss, and number of hairs shed while combing in treatment group; 84.8% in treatment group vs. 36.4% placebo group reported treatment satisfaction at 6 months | No AEs |
| Bussoletti et al. [19], 2011 | AGA | Caffeine shampoo | NA | 30 | 2 | Cohort study | Number of hairs extracted in hair-pull test decreased 7.17% after 3 months and 13.15% after 6 months; 67% were satisfied with the product | No AEs |
| Bussoletti et al. [20], 2018 | AGA | Caffeine shampoo | Control shampoo | NR | 1 | Double-blind RCT | Fewer hairs pulled in a hair-pull test at 6 months, compared with subjects using the control shampoo (−3.1 vs. −0.5 hairs) | No AEs |
| Bussoletti et al. [21], 2011 | AGA | Caffeine lotion | NA | 40 | 2 | Cohort study | Decrease in the number of hairs extracted with the hair-pull test by 8.14% after 2 months and 15.33% after 4 months Decrease in 75% of patients after 2 months and 83% after 4 months |
No AEs |
| Dhurat [22], 2017 | AGA | Caffeine 0.2% topical liquid | MXD 5% | 210 | 1 | Open-label RCT | After 6 months, mean improvement in anagen ratio was 10.59% in the caffeine group vs. 11.68% in the MXD group (p = 0.574) | Headache (n = 1) in MXD cohort |
| Golpour et al. [23], 2013 | AGA | Caffeine + MXD 2.5% solution | MXD 2.5% solution | 60 | 1 | Double-blind RCT | After day 120, caffeine + MXD was more effective than MXD alone Prior to day 120, no statistically significant difference: 58.33% of patients (21/24) in caffeine + MXD group were satisfied with treatment vs. 41.37% (20/29) with MXD alone | Burning sensation and erythema (n = 6) in MXD group |
| Pazoki-Toroudi et al. [24], 2013 | AGA | Caffeine 1% + MXD 5% + azelaic acid 1.5% vs. MXD 5% | Placebo | 71 | 1 | Double-blind RCT | At 12 weeks, the solution consisting of caffeine 1%, MXD 5%, and azelaic acid 1.5% was found to be superior to MXD alone Dermatologist objective assessment and patient subjective self-assessment responses were significantly more positive in the combined topical solution group | No AEs |
| Harada et al. [26], 2007 | AA/AT/AGA | Capsaicin and isoflavone | Placebo (olive oil and dextrin) | 48 | 3 | Cohort study | Significant increase in IGF-I serum levels in treatment group vs. placebo Hair growth in 20/31 (64.5%) of capsaicin and isoflavone-treated groups compared to 11.8% of placebo | No AEs |
| Hordinsky et al. [27], 2004 | AA | Capsaicin cream (0.075%) | NA | 2 | 4 | Case series | Vellus hair regrowth by day 21 | Burning pain sensation (n = 2) |
| Yilmaz et al. [28], 2002 | AA | Capsaicin cream (0.075%) | NA | 14 | 2 | Cohort study | 7/14 (50%) reported hair growth after 3 weeks | No AEs |
| Ehsani et al. [29], 2009 | AA | Capsaicin ointment | Clobetasol 0.05% ointment | 50 | 1 | RCT | Significant increase in vellus and noncosmetic hair growth, but not cosmetically significant hairs | AEs: eczematous reaction (n = 1) |
| Harada et al. [30], 2008 | AA/AGA | Topical raspberry ketone (0.01%) | NA | 10 | 3 | Cohort study | Promoted hair regrowth in 50.0% (5/10) | No AEs |
| Pumthong et al. [32], 2012 | AGA | 5% topical hexane extract of Curcuma aeruginosa (turmeric) vs. 5% MXD vs. combination therapy | Hair tonic base | 87 | 1 | Double-blind RCT | TAHC: after 6 months, no significant improvement in any group when compared to placebo On photographic review, combination therapy and 5% MXD showed statistically significant results Subjective assessment of hair regrowth/shedding: only combination group statistically significant |
Itch reported (n = 1) |
| Hajheydari et al. [35], 2007 | AA | 5% garlic gel + betamethasone cream | Placebo gel | 40 | 1 | Double-blind RCT | After 3 months, good and moderate responses were observed in 19 (95%) of the garlic gel cohort and 1 (5%) in the placebo cohort | No AEs |
| Lassus and Eskelinen [36], 1992 | AGA | Marine extract (Viviscal®) | Fish extract | 40 | 1 | Double-blind RCT | 95% of patients had both clinical and histological improvements Mean increase of nonvellus hair of 38% after 6 months | No AEs |
| Lassus and Santalahti [37], 1992 | AA/AT | Marine extract (Viviscal®) | NA | 40 | 2 | Cohort study | 85% of AA patients showed improvement 45% of AT patients showed significant improvement |
No AEs |
| Lassus et al. [40], 1994 | AGA | Marine extract (Viviscal®) supplement and shampoo | NA | 30 | 2 | Cohort study | Hair loss decreased for 100% of patients after 2 months 92% of patients showed signs of hair growth | All patients had mild to moderate dying of the scalp |
| Majass et al. [41], 1996 | AA/AT/AU | Marine extract (Viviscal®) | NA | 84 | 2 | Cohort study | 92% of AA, 83.3% of AT, and 31.8% of AU patients showed signs of hair growth after 6 months | No AEs |
| Pereira [42], 1997 | AGA | Marine extract (Viviscal®) 600 mg daily | NA | 200 | 2 | Cohort study | After 6 months, 75.3% of patients had a significant decrease in hair loss and 14.6% had partial regrowth | No AEs |
| Thom [43], 2001 | AGA and AA | Marine extract (Hairgain®) | Placebo | 60 | 1 | Double-blind RCT | After 6 months, hair growth increased 32.4% with Hairgain® compared to 0.9% with placebo After 12 months, hair growth increased 63.9% No response seen in the 4 patients with AT |
No AEs |
| Stephens & Associates [44], 2010 | FPHL | Marine extract (Viviscal®) | NA | 16 | 2 | Cohort study | After 10 weeks, 46% reduction in hair loss 75% reported increased thickness in the body of the hair 75% increase in overall hair volume |
Headache (n = 1) |
| Jackson [45], 2011 | FPHL (AA) |
Marine extract (Viviscal®) | NA | 16 | 2 | Cohort study | Greatest change in hair growth and quality occurred during first 2 months Decrease in hair shedding |
No AEs |
| Ablon [46], 2012 | FPHL | Marine extract (Viviscal®) | Placebo | 15 | 1 | Double-blind RCT | 111% increase in terminal hairs after 3 months vs. no change with placebo 125% increase in terminal hairs after 6 months vs. no change with placebo After 3 and 6 months, improvement in overall hair volume, thickness, and scalp coverage |
No AEs |
| Stephens & Associates [47], 2013 | FPHL | Marine extract (Viviscal®) | Placebo | 72 | 1 | Double-blind RCT | 7.4% increase in hair diameter after 6 months 8.3% reduction in hair shedding after 3 months | No AEs |
| Bloch [48], 2014 | FPHL | Marine extract (Viviscal®) | NA | 52 | 2 | Cohort study | After 6 months, improvement in hair volume (94%), hair thickness (92%), nail growth rate (91%), and nail strength (92%) | No AEs |
| Ablon [49], 2015 | FPHL | Marine extract (Viviscal®) | Placebo | 60 | 1 | Double-blind RCT | After 3 months, 32% increase in mean number of terminal hairs, 8.2% increase in vellus hairs, 39% reduction in hair shedding, and increase in quality of life scores | No AEs |
| Ablon and Dayan [38], 2015 | FPHL | Marine extract (Viviscal®) | Placebo | 40 | 1 | Double-blind RCT | After 3 months, 57% increase in terminal hairs After 6 months, 80% increase in terminal hairs and 12% increase in hair diameter |
No AEs |
| Rizer et al. [50], 2015 | FPHL | Marine extract (Viviscal®) | Placebo | 96 | 1 | Double-blind RCT | Hair shedding was significantly reduced from 52.1 at baseline to 42.6 at 3 months and 42.7 at 6 months with increase in mean hair diameter of vellus-like hairs | No AEs |
| Ablon [51], 2016 | AGA | Marine extract (Viviscal®) | Placebo | 60 | 1 | Double-blind RCT | Significant increase in total hair count, total hair density, and terminal hair density after 180 days Hair-pull test significantly lower in treatment group |
No AEs |
| Fischer et al. [53], 2004 | AGA and diffuse alopecia | Melatonin 0.1% solution | Placebo | 40 | 1 | Double-blind RCT | Increased anagen hair rate in occipital hair in women with AGA Increased anagen hair rate in frontal hair in women with diffuse alopecia | No AEs |
| Fischer et al. [54], 2012 | AGA | Melatonin 0.0033% solution | NA | 30 | 2 | Cohort study | Significant reduction in alopecia after 30 days and 90 days | No AEs |
| Fischer et al. [54], 2012 | AGA | Melatonin 0.0033% solution | NA | 35 | 2 | Cohort study | 29.2% increase in hair count in 54.8% of patients and 29.1% increase in hair density in 54.8% after 3 months 42.7% increase in hair count in 58.1% of patients and 40.9% improved hair density in 58.1% after 6 months |
Occasional itchiness |
| Fischer et al. [54], 2012 | AGA | Melatonin 0.0033% solution | NA | 60 | 2 | Cohort study | Significant improvement in hair texture and reduced hair loss | Temporary reddening, sensitivity, itching, or burning (n = 4) |
| Fischer et al. [54], 2012 | AGA | Melatonin 0.0033% solution | NA | 1,891 | 2 | Cohort study | Significant decrease in patients with severe and moderately severe hair loss: from 61.6 to 33.7% after 30 days to 7.8% after 90 days Increase in patients with no hair loss: increased from 12.2 to 25.5% after 30 days to 61.5% after 90 days Improvement in seborrhea |
No AEs |
| Sharique and Al-Obaidi [55], 2002 | AA | Onion juice | Tap water | 62 | 2 | Single-blind, placebo-controlled trial | At week 8, full hair regrowth seen in 86.9% patients with onion juice vs. 13.3% with tap water | Mild erythema in 60.8% of patients (14/23) in the onion juice cohort. Unpleasant odor |
| Kamimura et al. [56], 2000 | AGA | Topical 1.0% procyanidin B-2 (apple juice) | Placebo | 29 | 1 | Double-blind RCT | Significantly greater increase in number of total hairs (6.68 vs. 0.08 for placebo) and number of terminal hairs (1.99 vs. −0.82 for placebo) compared to placebo after 6 months | No AEs |
| Takahashi et al. [58], 2001 | AGA | Topical 1.0% procyanidin B2 (apple juice) | Placebo | 29 | 1 | Double-blind RCT | Significantly greater increase in hair counts after 4 months (3.67 vs. −2.54 for placebo) 78.9% showed increase in hair diameter vs. 30.0% for placebo |
No AEs |
| Takahashi et al. [59], 2005 | AGA | Topical 0.7% procyanidin (apple juice) | Placebo | 43 | 1 | Double-blind RCT | Significantly greater increase in hair counts after 6 months (3.3 vs. −3.6 for placebo) Total increase of 23 hairs/cm2 after 12 months |
No AEs |
| Tenore et al. [60], 2018 | AGA | Oral procyanidin: AFA polyphenolic extract 400 mg (AMS) + biotin, selenomethionine (AMSbzs) | Maltodextrin tablets | 250 | 1 | Double-blind RCT | Both supplement groups improved all clinical parameters at 1 and 2 months Specifically, AMSbzs increased the hair number/cm2 by 125.2%, the hair weight by 42.1%, and the keratin content by 40.1% at 2 months |
No AEs |
| Cho et al. [64], 2014 | AGA | Pumpkin seed oil (400 mg daily) | Placebo | 76 | 1 | Double-blind RCT | After 24 weeks, mean increase in hair count of 40% compared to 10% with placebo Patient-reported improvement and satisfaction scores were higher than placebo |
AEs: pruritus (n = 2), abdominal discomfort (n = 1) |
| Panahi et al. [66], 2015 | AGA | Rosemary oil lotion (3.7 mg/mL 1,8-cinole) | MXD 2% | 100 | 1 | RCT | Rosemary oil was noninferior to minoxidil Both groups had significant increase in hair count at 6 months |
No AEs |
| Prager et al. [69], 2002 | AGA | Saw palmetto (Serenoa repens) 200 mg + 50 mg β-sitosterol × 21 weeks | Placebo | 26 | 2 | Double-blind RCT | 60% of patients (6/10) with “improved” outcomes compared to baseline, vs. 11% (1/9) for control | AEs reported: Treatment group: acne (n = 1) GI symptoms (n = 3); Placebo group: frequent urination (n = 1), lightheadedness (n = 1), heightened sensations (n = 1), awareness of heartbeat (n = 1) |
| Rossi et al. [70], 2012 | AGA | Saw palmetto (S. repens) 320 mg daily × 24 months |
Finasteride 1 mg daily | 100 | 1 | RCT | Hair growth score higher in the finasteride group 38% of patients treated with S. repens had an increase in hair growth (mainly on the vertex) 68% of those treated with finasteride noted an improvement Effect of S. repens over the frontal area was inferior to finasteride |
No AEs |
| Wessaagowit et al. [71], 2016 | AGA | Topical saw palmetto (S. repens) concentrated serum, 3.3 mL × 4 weeks, lotion, 2 mL × 24 weeks | NA | 50 | 2 | Cohort study | Average hair count and terminal hair count increased at weeks 12 and 24 compared to baseline | Reported AEs: feeling of coldness (16%), mild burning (12%), an unpleasant smell (2%), an itchy scalp (2%), acne on the forehead (2%), and abrasion when using the finger that touched the products to scratch the scrotum (2%) |
| Berth-Jones and Hutchinson [88], 2009 | AT/AU | Vitamin D (calcipotriol ointment 50 µg/g applied b.i.d. for 6 months) | Placebo | 20 | 1 | Double-blind RCT | No response to calcipotriol in patients with AT or AU | AEs: pruritus with or without erythema (n = 8), eczema (n = 1) |
| Orecchia and Rocchetti [89], 1995 | AA/AU/AT | Vitamin D (calcipotriol ointment 50 µg/g applied daily for 6 months) | NA | 28 | 2 | Cohort study | Failure of calcipotriol to potentiate squaric acid dibutylester effectiveness | AEs: redness and/or scaling (n = 15) |
| Kim et al. [90], 2012 | AA | Vitamin D (calcipotriol topical solution 50 µg/mL applied daily for 3 months) | NA | 1 | 5 | Case report | Complete hair regrowth at 3 months No relapse at 9 months | No AEs |
| Çerman et al. [91], 2015 | AA | Vitamin D (topical calcipotriol 0.005% b.i.d. for 12 weeks) | NA | 48 | 3 | Cohort study | Significantly lower SALT score at 12 weeks compared to baseline Hair regrowth greater than >50% seen in 75% of patients, hair regrowth of >75% seen in 62.5%, and complete regrowth in 27.1% |
No AEs |
| Narang et al. [92], 2017 | AA | Vitamin D (topical calcipotriol 0.005% b.i.d. for 12 weeks) | NA | 22 | 2 | Cohort study | 59.1% of patients had hair regrowth, with onset at 4.21 ± 2.13 weeks 9 patients with 0% change, 4 patients with 25% change, 3 patients with 26–50% change, 6 patients with >50% change | AEs seen in 7/22 (31.8%) patients: irritation, scaling, erythema, pruritus, pigmentation, and folliculitis |
| Beoy et al. [94], 2010 | “hair loss” | Mixed tocotrienols (Vitamin E) 50 mg mixed, plus 23 IU of α-tocopherol |
Placebo | 38 | 1 | Double-blind RCT | After 8 months, 34.5% increase in number of hairs after 8-month supplementation compared to 0.1% for placebo | No AEs |
| Berger et al. [102], 2003 | AGA | 1% pyrithione zinc shampoo daily, 1% pyrithione zinc daily + 5% MXD b.i.d., and 5% MXD b.i.d. | Placebo | 200 | 1 | RCT | All treatment groups showed increase in hair counts at 9 weeks Increase in hair count for pyrithione zinc was less than half that of MXD No increase in hair count with combination therapy vs. MXD | No AEs |
| Siavash et al. [103], 2017 | AGA | Zinc sulfate 50 mg/day, calcium pantothenate 100 mg/day or 1 mL 2% MXD b.i.d. |
NA | 73 | 1 | RCT | Positive outcomes reported in all treatment groups 2% MXD resulted in a greater increase in hair density Oral zinc and pantothenate resulted in thicker hair shafts | Dandruff (n = 3) and pruritus (n = 3) in the minoxidil group |
| Park et al. [104], 2009 | AA (with low zinc levels) | Zinc gluconate 50 mg/day | NA | 20 | 2 | Cohort study | After 12 weeks, cosmetic satisfaction or terminal hair growth in 9/15 patients | Nausea (n = 2) |
| Alhaj et al. [105], 2007 | AA (with low zinc levels) | Zinc 50 mg/day | NA | 1 | 5 | Case report | Zinc supplementation in a 4-year-old child resulted in resolution of hair loss after 3 weeks and was maintained for 4 months | No AEs |
| Sharquie et al. [106], 2012 | AA | Zinc sulfate (5 mg/kg/day) | Placebo | 100 | 1 | Double-blind RCT | Zinc, then placebo: complete hair regrowth in 60% of patients after 3 months of zinc Placebo, then zinc: after 3 months of placebo, 10% of patients completely regrew hair; supplementation with zinc for 3 months resulted in 67% of patients with complete regrowth |
Mild gastric upset in 8 (11.6%) patients |
| Mind and Body Medicine | ||||||||
| Ge [112], 1990 | AA | Acupuncture | NA | 9 | 4 | Case series | Complete regrowth in 8/9 patients | No AEs |
| Zhu and Wu [113], 2011 | AA | Acupuncture | Cystine 0.1 g and vitamin B1 20 mg t.i.d., 2% MXD b.i.d. | 78 | 1 | RCT | Total hair regrowth in 58.1 vs. 34.3% for control Greater than 70% regrowth in 30 vs. 31% for control | No AEs |
| Yoon [114], 2014 | AGA | Acupuncture, pharmacopuncture, needle-embedding | NA | 1 | 5 | Case report | Hair loss improved “remarkably” | No AEs |
| Hay et al. [115], 1998 | AA | Aromatherapy (thyme, rosemary, lavender, and cedarwood) | Carrier oils | 86 | 1 | Double-blind RCT | 19/43 (44%) showed improvement vs. control 6/41 (15%) | No AEs |
| Putt et al. [117], 1994 | AA | Massage, relaxation | NA | 1 | 5 | Case report | Full hair regrowth | No AEs |
| Willemsen et al. [118], 2006 | AA | Hypnotherapy | NA | 21 | 4 | Case series | Significant hair regrowth in 12 patients after 3–8 sessions Total hair regrowth in 9 patients. Relapse occurred in 5 patients | No AEs |
| Harrison and Stepanek [119], 1991 | AA | Hypnotherapy | NA | 12 | 4 | Case series | Of the 5 patients that completed the study, only 1 saw “significant hair growth” and 3 had minimal regrowth | No AEs |
| Willemsen et al. [120], 2010 | AA | Hypnotherapy | Control | 41 | 2 | Cohort study | Improvement in depression and anxiety 8 patients had a nonsignificant hair regrowth of <50% | No AEs |
| Teshima et al. [122], 1991 | AU | Psychotherapy | Immunotherapy | 11 | 4 | Case series | 5/6 patients with combination therapy (psychotherapy + immunotherapy) had full regrowth vs. 1/6 with immunotherapy alone | No AEs |
| Other | ||||||||
| Anninos et al. [125, 126], 2005, 2004 | AU | Transcranial magnetic stimulation | NA | 3 | 5 | Case reports | Diffuse hair regrowth (mainly parietal and occipital areas) | No AEs |
| Bureau et al. [127], 2003 | AGA | Essential oils + low-intensity electromagnetic pulses | Control | 69 | 1 | Double-blind RCT | After 26 weeks, mean hair counts were significantly improved in the treatment group compared to control | No AEs |
| Itamura [129], 2007 | AA | Homeopathy (Mercurius) | NA | 1 | 5 | Case report | After 3 months, significant (75%) improvement per patient | No AEs |
| Shaoqiong et al. [130], 2005 | AA | Traditional Chinese medicine concoction | NA | 1 | 5 | Case report | After 3 months, scalp hairs grew to 7 cm | Scalp pruritus |
AA, alopecia areata; AEs, adverse events; AGA, androgenetic alopecia ALT, alternative; AMS, Annurca apple polyphenolic extract microencapsulated with maltodextrins (AppleMetS); AMSbzs, Annurca apple polyphenolic extract microencapsulated with maltodextrins, biotin, selenium, and zinc; AT, alopecia totalis; AU, alopecia universalis; b.i.d., twice daily; COMP, complementary; MXD, minoxidil; NA, not applicable; NR, not reported; RCT, randomized clinical trial; TAHC, total area hair count; t.i.d., 3 times a day. ª Quality rating scale (1–5) is modified from the Oxford Centre of Evidence-Based Medicine for ratings of individual studies: 1 - properly powered and conducted randomized clinical trial; systematic review with meta-analysis; 2 - well-designed controlled trial without randomization; prospective comparative cohort trial (including low-quality RCT); 3 - case-control studies; retrospective cohort study; 4 - case series with or without intervention; cross-sectional study; 5 - opinion of respected authorities; case reports.