Ingredients of Trichological Shampoos with Alleged Beneficial Effects on Hair—What Is Really Known About Their Efficacy? A Scoping Review of an Area with More Unknowns than Knowns

Abstract

Numerous ingredients in trichological shampoos are advertised as “active against hair loss”; however, the body of evidence behind such claims seems very limited or, in many cases, nonexistent. The aim of this study was to compile an inventory of substances advertised by shampoo manufacturers as “active” against hair loss and systematically review available evidence from clinical trials that would corroborate such claims. We screened declared compositions of trichological shampoos for ingredients advertised as active against hair loss or promoting hair growth. The second step was a systematic review of clinical trials of these substances used topically in the treatment of hair loss. A query in PubMed, Scopus, and Web of Science followed PRISMA and PICO guidelines with the strength of evidence assessed according to GRADE guidelines. We identified 43 trichological shampoos in which 112 individual ingredients were advertised as “active”. Of these, 36 ingredients were indicated as “active” in at least two shampoos and were subject to further study. In the search for evidence, 103,639 articles were screened for relevant information. Ultimately, we identified 29 clinical trials that tested 16 of the 36 ingredients for efficacy against hair loss. Only four ingredients were tested individually: adenosine (four trials; highest strength of evidence: moderate), caffeine (four trials; moderate), placental protein (two trials; low), and melatonin (one trial; moderate). Another 12 ingredients of interest were only tested as parts of complex preparations: Achillea millefolium extract, arginine, biotin, hydrolyzed wheat protein, hydrolyzed soy protein, Panax ginseng, panthenol, piroctone olamine, Prunus amygdalus dulcis, Rosmarinus officinalis, Serenoa serrulata, and Urtica dioica. Such a study design made it impossible to attribute the observed effects to any specific ingredient. No clinical trials of efficacy could be found for the remaining 20 (55.6%) substances repeatedly cited as “active”. At the present stage, scientific evidence for efficacy against hair loss is available only for caffeine, adenosine, placental proteins, and melatonin, but the overall strength of evidence is low. Moreover, a substantial majority of topical ingredients promoted as “active against hair loss” were never actually tested in clinical trials to verify such claims. While unsubstantiated claims of supposed beneficial properties often refer to alleged scientific evidence, there are major gaps to be filled in the field of non-prescription treatments for hair loss.

1. Introduction

Hair loss is a physiological phenomenon, but excessive hair loss can lead to visible thinning and even baldness, causing serious psychological distress and reduced quality of life [1]. It may be a sequela of nutritional deficiency or serious diseases or a side effect of pharmacotherapy, including cancer treatment [1,2,3,4,5,6]. To date, the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have only approved topical minoxidil and oral finasteride for the treatment of baldness [7]. Due to its adverse hormonal effects, finasteride is approved for treatment only in men [8]. This is in spite of the fact that emerging evidence suggests efficacy of both oral minoxidil and topical finasteride as well as of oral finasteride in female pattern hair loss (FPHL) [9,10,11]. Other pharmacological off-label modalities with emerging evidence of efficacy in hair loss are spironolactone and dutasteride [12,13]. Numerous other treatment modalities have been discussed, including topical ketoconazole, isotretinoin, botulinum toxin type A, melatonin, pirfenidone, prostaglandin E2 (PGE2) and the PGF2α analogs bimatoprost and latanoprost, cetirizine, Janus kinase (JAK) inhibitors, adenosine, caffeine, veratric acid, nutritional supplements, botulinum toxin, platelet-rich plasma, radiofrequency (RF) electric currents, low-level laser therapy, autologous stem cells, exosomes, and combination therapies [14,15,16,17,18,19,20,21,22,23]. Next to legal considerations with regard to off-label treatments, concerns about drug safety and possible adverse effects of pharmacotherapy seem to be factors discouraging patients and some doctors from initiating hair loss therapy with pharmacologic agents [24,25,26]. The fear of “chemical” therapies voiced by many patients has sparked a renaissance of natural ingredients in drugs and cosmetics because products of “natural origin” are in high demand [27]. Herbal remedies have been used for centuries, and they are still sought for due to the general reception of “natural” as “safe” [28]. In response to this demand, industry searches for complementary and alternative therapies with better effectiveness and less adverse effects than the therapies approved nowadays [29]. This trend is also reflected in the realm of topical products against hair loss, referred to as “trichological products”—a term supposed to underscore their intended superiority over common hair care products. According to Trüeb et al., the term “trichology” emerged around 1902, referring to the knowledge taught to people pursuing the practice of hair care and treatment of human hair and scalp in health and disease, who otherwise were not medically qualified or licensed [30]. In the indexed medical literature, the adjective “trichological” was first used by Camacho et al. in 1978 (in French) and Plewig et al. in 1979 (in German) in reference to the clinical investigation of hair [31,32]. By 2000, the term appeared altogether in only ten PubMed-indexed articles (also in English and Polish), including four articles in which it featured in titles [32,33,34,35]. With the advent of the “International Journal of Trichology (IJT)” in 2009, the term “trichology” eventually entered the mainstream medical vocabulary [36]. As of 30 July 2025, PubMed listed 1061 articles featuring the terms “trichology” or “trichological” in any indexed field, including 36 article titles. On the other hand, the presence of these terms in the scientific literature seems to have boosted their use in marketing, which has contributed to a dilution of their meaning and amplifying their unscientific and mercantile aspects [37,38]. This is also the impression when looking at topical trichological products, i.e., shampoos, lotions, tonics, solutions, liquids, foams, and serums presented by producers and resellers as allegedly more “specialist”, “professional”, and “science-based” [39].

In our preliminary study [40], we observed that virtually all producers of trichological shampoos boasted about a range of ingredients supposed to be “active” against hair loss. The majority of these ingredients were of organic origin, ranging from well-defined biomolecules like adenosine and caffeine to complex and less standardized plant and animal organ extracts. A critical look at the ingredient lists led us to a suspicion that many of them have not actually undergone clinical trials that would confirm their alleged activity. This notion was seminal for a series of systematic reviews in order to collate and critically assess the evidence behind claims of the ingredients’ beneficial effects on the hair. Recently, we published systematic reviews of topical agents with the most numerous (albeit still relatively few) clinical trials in hair loss: placenta derivatives, caffeine, and adenosine [14,18,41]. The aim of the present scoping review was to conclude this cycle by collating the evidence with regard to the remaining topical ingredients advertised as active against hair loss and to map the knowledge gaps in this area.

In the present article, the umbrella term “topical trichological products” will be used when referring collectively to all products—either rinse-off or leave-on—that are applied to the scalp for the purpose of preventing hair loss or promoting hair growth and declared by the producers as “trichological”, i.e., possessing special, “science-based” or “scientifically proven” properties that allegedly put these products above “ordinary” hair care products. Topical trichological products can be divided into two types: rinse-off products, represented by “trichological shampoos” intended for a short (minutes) period of contact with the scalp while washing hair, and “trichological leave-on products” that are intended to be left on the skin for a longer period (hours). These leave-on products may come in the form of solutions, lotions, liquids, serums, tonics, foams, etc.

2. Materials and Methods

2.1. Compilation of an Inventory of Ingredients Declared as Active in Trichological Shampoos

Trichological shampoos offered online in Poland between January and December 2024 were identified using the Google search engine by combining phrases like “trichological shampoo(s)”, “trichological preparation(s)”, “against hair loss”, “against baldness”, “stimulating hair regrowth”, “trichological company”, or “trichology company” in the Polish language. Products were included in further analysis if (1) they were distributed exclusively through trichologist offices, (2) the manufacturer unequivocally declared that the shampoo was effective against hair loss or promoted hair growth by using phrases like “against hair loss”, “against alopecia”, “against effluvium”, “preventing hair loss”, “strengthening hair”, “inhibiting hair loss”, and “stimulating hair growth” in Polish or English, and (3) a complete INCI list of ingredients was available from the manufacturer’s website. Next, a list was compiled of ingredients that were indicated as “active” by at least one producer. Based on experience from our previous research, we predicted that there would be a multitude of various ingredients indicated as “active” in individual products [39]. Therefore, further analyses were limited to ingredients declared as “active” in at least 2 shampoos.

2.2. Evidence Acquisition from Published Clinical Trials

A scoping review was conducted according to PRISMA and PICO protocols from January 2025 to July 2025. The protocol of the scoping review was registered and made public in the Open Science Framework (OSF) database [42]. Scientific publications indexed in PubMed, Web of Science, and Scopus were searched using the query “X AND (hair OR alopecia OR effluvium OR bald OR baldness OR pilo* OR pili)”, where “X” was substituted with the names of substances from the list described above. For each substance, the INCI name was used in the query, as well as synonyms retrieved from the PubChem chemistry database (National Institutes of Health, Bethesda, MD, USA). In all queries, the “all fields” option was enabled. No additional filters were used, such as language or publication date. After removing duplicates, the retrieved articles underwent an initial screening by title and abstract. Articles selected in this step underwent a second, full-text review done independently by both authors to select articles that met the inclusion criteria. For articles selected by only one co-author, consensus was reached through discussion. In the case of trial reports selected in the described way, their reference lists and “similar articles” listed in PubMed were additionally screened for relevant articles.

2.3. Inclusion and Exclusion Criteria

This analysis included publications presenting the results of clinical trials on the effectiveness of topical substances of interest in patients with hair loss. In order to ensure the scientific integrity in this rather commercially biased area, only original articles published in peer-reviewed journals were included. Review articles, conference abstracts, posters, meeting reports, and gray literature were excluded from the present study. Due to the scarcity of clinical trials in this area, no further exclusion criteria were applied, such as lack of a control group or blinding, nor a sample size threshold.

2.4. Assessing the Strength of Evidence and Retrieving Relevant Data

The GRADE classification system was used to assess the strength of evidence in the included studies on a scale ranging from very low, through low and moderate, to high [43]. Data relevant to this review were extracted into pre-designed tables reflecting the PICO criteria (

Table 1. Inclusion criteria for the human studies covered in this systematic review.

PICO Criterion	Description
Patients/Participants	People suffering from baldness, hair loss, effluvium, or alopecia
Intervention	Ingredients of interest tested in topical anti-hair loss preparations
Comparator/Control	Placebo or other topical anti-hair loss preparations, no comparator
Outcomes	Phototrichogram, trichoscopy, investigator assessment (IA), participant assessment (PA)

).

When assessing the strength of evidence, special attention was paid to the study design, information on the concentration of the tested substance, the route of administration and formulation, as well as the outcome measures selected. The entire search and selection process is presented in Figure 1.

3. Results

3.1. Ingredients Advertised as “Active” in Trichological Shampoos

Forty-three trichological shampoos of 17 brands from six countries fulfilled the inclusion criteria. Italian products predominated, with 16 trichological shampoos offered on the Polish market in the observation period, followed by 12 from Spain, 6 from Poland, 4 from Taiwan, 4 from the USA, and 1 from The Netherlands. In those 43 trichological shampoos, a total of 112 unique ingredients declared by at least one manufacturer as “active” were identified, 76 of which were indicated each in only one product. To ensure the feasibility of the project, the subsequent search for evidence was limited to 36 (32.1%) ingredients that were declared as “active against hair loss” in two or more trichological shampoos (

Table 2. Ingredients declared by the manufacturer as “active against hair loss” that were present in at least two of the forty-three analyzed trichological shampoos.

Ingredient	CAS Number	Origin	N	A
Achillea millefolium extract	84082-83-7	Plant	5	4
Adenosine	58-61-7	Animal, various	3	3
Aloe barbadensis	85507-69-3	Plant	6	2
Arginine	74-79-3	Synthetic, plant, animal	4	4
Biotin	58-85-5	Synthetic, plant	10	2
Caffeine	58-08-2	Synthetic, plant	7	6
Calcium pantothenate	137-08-6	Synthetic, natural	5	2
Capsicum	85940-30-3	Plant	9	7
Cinchona succirubra bark extract	84776-28-3	Plant	3	3
Citrus paradisi extract	90045-43-5	Plant	2	2
Gardenia jasminoides meristem cell culture	-	Plant	2	2
Glycine soja germ extract	-	Plant	2	2
Humulus lupulus extract	8060-28-4	Plant	5	2
Hydrolyzed collagen	92113-31-0	Animal	5	4
Hydrolyzed keratin	69430-36-0	Animal, plant	6	2
Hydrolyzed soy protein	68607-88-5	Plant	5	2
Hydrolyzed wheat protein	94350-06-8	Plant	6	2
Lavandula angustifolia oil	8000-28-0	Plant	2	2
Melaleuca ericifolia oil	85085-48-9	Plant	2	2
Malus domestica fruit cell culture	-	Plant	5	3
Medicago sativa extract	84082-36-0	Plant	2	2
Melatonin	73-31-4	Synthetic	4	3
Menthol	1490-04-6	Plant	11	3
Panax ginseng root extract	84650-12-4	Plant	6	2
Panicum miliaceum	90082-36-3	Plant	2	2
Panthenol	81-13-0	Synthetic	23	2
Piroctone olamine	68890-66-4	Synthetic	2	2
Placental protein	84195-59-5	Animal	5	3
Prunus amygdalus dulcis oil	8007-69-0	Plant	4	4
Rosmarinus officinalis leaf extract	84604-14-8	Plant	9	6
Royal jelly	8031-67-2	Animal	2	2
Serenoa serrulata fruit extract	84604-15-9	Plant	11	8
Tocopherol	1406-66-2	Plant, synthetic	7	2
Tocopheryl acetate	7695-91-2	Plant, synthetic	11	2
Tussilago farfara extract	84625-50-3	Plant	3	3
Urtica dioica extract	84012-40-8	Plant	9	3

Abbreviations: CAS—Chemical Abstracts Service; N—number of trichological shampoos that according to the manufacturer’s declaration contained the given ingredient of interest; A—number of trichological shampoos in which the given ingredient was advertised as “active”.

).

3.2. Published Evidence Behind the “Active” Ingredients in Trichological Shampoos

The bibliographic query returned altogether 103,639 articles mentioning one or more of the thirty-six ingredients compiled in the first step, of which 19,928 duplicates were excluded. After reading the abstracts, a further 83,711 articles were excluded as not fulfilling the inclusion criteria. The remaining 609 articles were read in full text, which ultimately resulted in the selection of 29 articles meeting the inclusion criteria. These were clinical trial reports of substances listed in Table 2, studied in participants with various types of hair loss defined as androgenetic alopecia (AGA, 22 studies, 3695 participants in total), telogen effluvium (TE, 3 studies, 154 participants), unspecified hair loss (3 studies, 107 participants), female pattern hair loss (FPHL, 2 studies, 46 participants), thinning hair (1 study, 84 participants), diffuse alopecia (DA, 1 study, 28 participants), and postpartum hair loss (1 study, 25 participants). Details on the hair problems in the study populations are presented in

Table 3. Types of hair loss included in the clinical trials of ingredients of interest.

Hair Problem	Main Features	Diagnostic Methods Used	Ref.
Androgenetic alopecia	Miniaturization of hair follicles in androgen-dependent areas	Dermatoscopy, trichoscopy	[44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65]
Telogen effluvium	It occurs about three months after the triggering factor, e.g., infection, drug use, hormonal disorders, metabolic diseases, nutritional deficiencies, or stress	Positive pull test, trichogram, laboratory tests for underlying conditions	[63,66,67]
Hair loss (unspecified)	Losing more hair than usual for longer than three months	Positive pull test, trichogram, laboratory tests for underlying conditions	[44,48,68]
Female pattern hair loss	Miniaturization of hair follicles in androgen-dependent areas	Dermatoscopy, trichoscopy	[50,69]
Thinning hair	A noticeable reduction in hair density	Dermatoscopy, trichoscopy	[70]
Diffuse alopecia	A large number of hairs prematurely entering the telogen phase, resulting in diffuse hair loss	Dermatoscopy, trichoscopy	[45]
Postpartum hair loss	Typically occurs about three months after childbirth	Positive pull test, trichogram, laboratory tests for underlying conditions	[71]

.

Eleven studies were identified that focused on single substances of interest: adenosine, caffeine, placental proteins, and melatonin. With regard to testing the efficacy of individual substances against hair loss, scientific evidence of varying strength according to the GRADE scale was available only for four ingredients: caffeine (four studies; highest strength of evidence: moderate), adenosine (four studies; moderate); placental proteins (two studies, moderate); and melatonin (one study; moderate). Ingredients tested individually in more than one clinical trial were presented in separate systematic reviews devoted to adenosine [18], caffeine [14], and placental proteins [41].

Adenosine was subject to four trials. In all four, it was tested in trichological leave-on products. In one trial, involving 94 males with AGA, the efficacy of 0.75% adenosine lotion was compared with 5% minoxidil lotion [60]. After 6 months of treatment, a complete recovery was not observed in any participant. Relative recovery (returning hair growth in 30% to 65% of the affected area) was noted in one participant (2.4%) of the MNX group and one participant (1.9%) of the adenosine group (p = 0.99, ns). This means that in the remaining participants in both groups the recovery rate was below 30%, which the authors interpreted as “no recovery or treatment failure”. On the other hand, the rate of patients satisfied with the treatment in the adenosine group (69.8%) was significantly higher than the minoxidil group (31.7%, p = 0.003). A possible explanation for this discrepancy might be the method of hair counting applied in the study that seems to not be validated, as it also failed to detect any effect of minoxidil, a well-established and officially approved topical treatment for hair loss [7]. Because of this weakness, the strength of evidence in this study was assessed as low, and obvious calculation errors constituted another reporting flaw in the paper (the percentages shown in Table S1 in the Supplementary Material were adjusted based on the raw data presented in the article) [60]. In a subsequent study of 38 men with AGA, after 6 months of treatment there was an increase in the mean proportion of thick hair (≥60 µm in diameter) by 5.5%, and hair density by 4.9% in the group receiving adenosine 0.75% lotion with a simultaneous decrease in these variables by 8.5% and 3.8% in the placebo group (p < 0.001 and 0.049, respectively). A parallel decrease was observed in the mean proportion of vellus hair by 1.4% in the adenosine group and an increase by 6.6% (p = 0.015) in the placebo group. The strength of evidence presented in this study was assessed as low [61]. A further study of 101 males with AGA compared the effects of adenosine lotion 0.75% with niacinamide lotion 0.1%. After 6 months, the mean ratio of thick hairs (analyzed both as ≥60 µm and ≥80 µm) rose in the adenosine group (10.4% and 5.1%, respectively), which was more than in the niacinamide group (6.1%, p = 0.033; 2.5%, p = 0.027). No significant differences were observed with regard to hair density and vellus hair. The strength of evidence in this study was rated as moderate [62]. Finally, one randomized, double-blind, placebo-controlled study with moderate strength of evidence looked into the efficacy of a lotion with adenosine 0.75% in 27 females with FPHL. After 12 months, “improvement” or “slight improvement” was pronounced in 85% of adenosine-treated patients, as compared with 36% patients from the placebo group (p = 0.024). The authors reported that the mean anagen hair growth rate in the adenosine group increased significantly both after 6 and 12 months of treatment (p = 0.014 and 0.031, respectively); however, no numerical values were given, only a graph that showed apparently minor differences. In the placebo group, the ratio of thick hair was reportedly reduced significantly over the observation period compared with the baseline (p = 0.006 after 6 months and 0.002 after 12 months). Also, for this outcome measure, no numerical values were disclosed, and only a difference of approximately 10 percentage points could be seen in the graph. An increasing, yet statistically nonsignificant trend was shown in the graph for the adenosine group [69]. In our previous work, we carried out a meta-analysis of data extracted from three of the above trials that showed a tendency to increased hair density (OR = 1.03, 95% CI: 0.89–1.20, p = 0.68), an increase in thick hair (OR = 1.4, 95% CI: 0.82–2.38, p = 0.21), and a decrease in thin hairs (OR = 0.93, 95% CI: 0.61–1.43, p = 0.75) after 6 months of alopecia treatment with a 0.75% adenosine lotion [18].

Topical caffeine as the sole molecule was tested for efficacy in four eligible clinical trials. In one of them, caffeine was tested in a trichological leave-on product (lotion), and in the remaining three it was applied in the form of shampoos (rinse-off). In a multicenter, prospective, randomized, open-label noninferiority trial, a leave-on solution with 0.2% caffeine was compared with 5% MNX in 161 males with AGA. After 6 months, the mean anagen rate increased by 10.6% in the adenosine group and by 11.7% in the MNX group (difference: 1.1 percentage points, ns). The strength of evidence in this study was assessed as moderate [55]. A further randomized, double-blind study compared a shampoo (rinse-off) with either caffeine (concentration not disclosed) or a placebo in 66 men with AGA. Among numerous, mainly subjective outcome measures (compare Table S1 in the Supplementary Material), the authors considered patients’ contentment as the primary efficacy parameter. After 6 months, the rates of both contentment with the shampoo, and intent to continue the treatment (each 84.8%), were in the caffeine group significantly higher than in the placebo group (each 36.4%, p < 0.001). Also, an investigator found a reduction in hair loss in 72.7% participants receiving caffeine shampoo, and in 33.3% of those treated with the placebo (p = 0.003). Due to inconsistent and incomplete reporting, this randomized study’s strength of evidence was assessed as low on the GRADE scale [56]. In a prospective, open-label, uncontrolled trial (strength of evidence: very low), 30 men with AGA applied a commercial shampoo with caffeine at an undisclosed concentration. After daily use for 6 months, the mean number of hairs lost in the pull test decreased from 20.07 at start down to 18.63 after 3 months (−7.5%) and 17.43 (−13.1%) after 6 months (each p < 0.001). At the end of the study, 67% of participants expressed their satisfaction with the product [57]. Finally, a caffeine-containing shampoo (concentration not stated) was tested in an uncontrolled, open-label trial involving 30 women with TE over a period of 6 months. On the pull test, the mean number of pulled hairs decreased from 21.2 at start down to 20.3 after 3 months (−4.2%, nonsignificant, ns) and 19.2 after 6 months (−9.4%, p = 0.003). The authors mentioned in the paper a range of other outcome measures with a declared significant change; however, no numerical values were presented for these variables [67]. The lack of a control group in this study significantly weakens the evidence, as TE is self-limiting in many cases; moreover, hair loss is subject to seasonal fluctuations [14].

With regard to placenta derivatives (INCI: placental protein, hydrolyzed placental protein), there were two dedicated trials, both presenting low strength of evidence. One double-blind, randomized controlled trial compared the efficacy of a commercial cow placenta tonic lotion (leave-on, undisclosed composition and conc.) with minoxidil 2% lotion in 74 women with AGA [54]. The percentage of patients who were rated as having “moderate” or “marked” growth was 44.2% in the cow placenta group and 32.2% in the minoxidil group (p = 0.90, ns). The authors reported a mean increase in hair count by 10.2 hairs per “area” (size not disclosed) in the cow placenta group and 10.9 hairs per “area” in the minoxidil group (p = 0.63, ns). However, the longitudinal analysis (before–after) for each group was missing, making it impossible to interpret the actual effect (percentage change), which led to a lower rating of the strength of evidence in this paper [54]. The second trial studied the influence of an in-house-prepared serum with porcine placenta extract (leave-on) on the regrowth rate of shaved hair in healthy humans with a second untreated shaved patch as a control [72]. Regrowth of shaved hair was reportedly significantly faster in the treated than untreated areas, with the mean growth rate higher by 23.6% after 2 weeks and by 55.7% after 1 month (each p < 0.05). Despite the elegant study design, we assessed the strength of the evidence as low, primarily because of doubts as to the extent to which regrowth of shaved hair in healthy volunteers is representative of hair regrowth in alopecia [41]. Furthermore, there is a considerable heterogeneity of products referred to as “placental proteins/hydrolysates” with regard to both the animal species and processing of the material; therefore, results from trials of one placenta product cannot be automatically transferred to other placenta products. The main conclusions from the previously published systematic reviews are summarized in

Table 4. Topical ingredients tested individually in clinical trials that were subject to previous systematic reviews in the series. More details are presented in Table S1 in the Supplementary Material.

Ingredient	Total Participants	GRADE	Overall Conclusions	Ref.
Adenosine	466	Tested individually: - moderate: 2 trials [62,69] - low: 2 trials [60,61] Tested in complex products: - low: 2 trials [64,70] - very low: 1 trial [63]	Published trials seem to support the effectiveness of topical adenosine products against hair loss Limited data from clinical trials Very low to moderate strength of evidence	[18]
Caffeine	684	Tested individually: - moderate: 1 trial [55] - low: 1 trial [56] - very low: 2 trials [57,67] Tested in complex products: - moderate: 2 trials [65,70] - very low: 3 trials [58,59,68]	Published trials seem to support the effectiveness of topical caffeine products against hair loss Limited data from clinical trials Very low to moderate strength of evidence	[14]
Placenta derivatives	127	Tested individually: - low: 2 trials [54,72] Tested in complex products: - very low: 1 trial [71]	Published trials seem to support the effectiveness of topical placenta products against hair loss Very limited data from clinical trials Very low to low strength of evidence	[41]

GRADE—strength of evidence expressed in the GRADE scale [43].

.

Beyond the three active substances listed in Table 4, we were able to identify one more trial that studied the efficacy of a single topical agent advertised as an active ingredient in trichological shampoos—melatonin [44]. This double-blind, randomized, placebo-controlled trial of melatonin 0.1% alcoholic solution (leave-on) involved 40 women with either AGA (12 participants) or diffuse alopecia (DA, 28 participants) divided into respective subgroups. The participants were further randomized to receive melatonin 1% alcoholic solution or alcohol solvent alone serving as a placebo. After 6 months of treatment in patients with AGA, the anagen (active growth) rate found in the occipital region was significantly higher in the melatonin group than in the placebo group. A reverse, yet nonsignificant trend was seen in the frontal region in these patients. On the other hand, after 6 months of treatment with melatonin in DA patients, a significantly higher anagen rate was reported in frontal hair of melatonin-treated patients as compared with the placebo group, with a nonsignificant reverse tendency in occipital hair [44]. In summarizing the findings, it seems that in women with AGA topical melatonin exerts beneficial effects on occipital, but not frontal, hair, whereas in DA it exerts beneficial effects on frontal, but not occipital, hair. However, due to the small study populations it seemed appropriate to assign moderate strength of evidence to this otherwise well-designed and well-reported study. The main results from the clinical trial of topical melatonin in hair loss are summarized in

Table 5. An overview of the double-blind, randomized, placebo-controlled study of the efficacy of topical melatonin in hair loss [44].

Patients	Intervention	Comparator	Outcome (Reviewers’ Summary)	GRADE
12 F with AGA	Melatonin 0.1% alcoholic solution (leave-on)	Alcohol	After 6 months of treatment, a significantly higher anagen rate (85.0%) in mean occipital hair of the melatonin-treated group than in the placebo group (82.1%, p = 0.012). A reverse tendency in frontal hair (80.4% versus 84.9%; ns).	moderate
28 F with DA	Melatonin 0.1% alcoholic solution (leave-on)	Alcohol	After 6 months of treatment, a significantly higher anagen rate (83.8%) in mean frontal hair of the melatonin-treated group than in the placebo group (81.1%, p = 0.046). A reverse tendency in occipital hair (83.7% versus 84.9%; ns).	moderate

Abbreviations: AGA—androgenic alopecia; DA—diffuse alopecia; ns—nonsignificant; GRADE—strength of evidence expressed in the GRADE scale [43].

.

Beyond adenosine, caffeine, placental proteins, and melatonin, another 12 substances out of the 36 listed in Table 2 were tested in trials only as ingredients of complex topical trichological products containing multiple substances considered “active”. This renders it impossible to attribute any observed effects to specific ingredients. This was the case of A. millefolium extract, which was tested in a complex mixture of 6 substances in one trial (strength of evidence: medium), arginine—5 to 23 substances (two trials; highest strength of evidence: very low), biotin—3 to 7 substances (seven trials; low), hydrolyzed wheat protein—23 substances (one trial; very low), hydrolyzed soy protein—23 substances (one trial; very low), P. ginseng—4 substances (one trial; moderate), panthenol—3 to 4 substances (two trials; low), piroctone olamine—3 to 5 substances (three trials; very low), P. amygdalus dulcis—23 substances (one trial; very low), R. officinalis—4 to 23 substances (two trials; moderate), S serrulata—4 to 27 substances (three trials; moderate), and U. dioica—6 substances (one trial; moderate). Some of the complex products also included adenosine, caffeine, placental proteins, or melatonin. Key features of these studies of complex topical trichological products are collated in

Table 6. An overview of clinical trials of complex topical trichological products containing substances of interest (underlined). More details are presented in Table S2 in the Supplementary Material.

Study Design	Patients	Intervention	Comparator	Major Outcomes	GRADE	Ref.
Single-center, uncontrolled	18 P with AGA, hair loss, and thinning hair	Marketed hair lotion (leave-on) with biotin, thioglycoran, HUCP 1, thurfyl nicotinate, sodium pantothenate (undiscl. conc.)	None	After 60 d: incr. anagen hair ratio (p < 0.001), incr. growth rate (p < 0.001).	very low	[48]
Single-center, open-label, uncontrolled	20 M with AGA	Lotion (leave-on) with piroctone olamine (0.25%), triclosan (0.3%)	None	HCD index sign. decr. after 6 m of treatment (−22.2%, p < 0.05) and further on. Negative logarithmic correlation (r = −0.64, p < 0.01) between time of treatment and HCD index.	very low	[51]
Single-center, open-label, uncontrolled	30 M and F with AGA	Lotion (leave-on) with melatonin 0.0033%, Ginkgo biloba (undiscl. conc.), biotin (undiscl. conc.)	None	IA of alopecia severity decr. after 30 d (−34.1%, p < 0.001) and 60 d (−39.0, p < 0.001). P assessment of alopecia severity decr. after 30 d (−68.3%, p < 0.001) and 60 d (−75.1%, p < 0.001).	very low	[44] 2
Single-center, open-label, uncontrolled	35 M with AGA			Incr. hair density after 3 m (+29.1%, p < 0.001) and 6 m (+40.9%, p < 0.001). Rate of P satisfied (mostly satisfied) with the shampoo 93.2% after 3 m and after 6 m.	very low
Multicenter, open-label, uncontrolled	60 M and F with hair loss or thinning hair			Hair stylist assessment after 90 d: impr. of hair texture score by 18.5% (p < 0.001), impr. hair loss score by 11.8% (p < 0.001).	very low
Multicenter, open-label, uncontrolled	1800 M and F with AGA			IA: proportion of P with severe and moderate hair loss decr. from 61.6% at the beginning to 33.7% after 30 d (p < 0.001) and to 7.8% after 90 d (p < 0.001). Proportion of P with no hair loss incr. from 12.2% to 25.5% after 30 d (p < 0.001) and 61.5% after 90 d (p < 0.001).	very low
Single-center, open-label, uncontrolled	50 M with AGA	Marketed serum (leave-on) and shampoo (rinse-off) with S. serrulata, green tea extract, peony root extract, piroctone olamine, oligopeptides (undiscl. conc.)	None	Sign. incr. in hair density after 6 w (+21.5%, p < 0.001) and 12 w (+74.1%, p < 0.001).	very low	[53]
Single-center, open-label, uncontrolled	25 F with postpartum hair loss	Shampoo (rinse-off) and tonic (leave-on) with equine placental growth factor (PIGF), pumpkin extract, panthenol, and niacinamide (undiscl. conc.)	None	After 3 m: increased vertex hair thickness (+5.6%, p = 0.028), increased occipital hair density (+8.1%, p < 0.001)	very low	[71]
Single-center, open-label, prospective uncontrolled	56 M and F with AGA (36 P)and TE (24 P)	Lotion (leave-on) with oleanolic acid, apigenin, biotinyl tripeptide-1, 2-4-diamino pyrimidine-3-oxide, adenosine, G. biloba, biotin (undiscl. conc.)	None	After 6 m, 79% of P reported reduced hair loss, 86% of P were satisfied with the results	very low	[63]
Single-center, randomized, placebo-controlled, single-blind	120 M and F with AGA	Shampoo (rinse-off) and solution (leave-on) with Urtica urens leaf extract, U. dioica root extract, Matricaria chamomilla flower extract, A. millefolium aerial part extract, Ceratonia siliqua fruit extract, Equisetum arvense leaf extract (undiscl. conc.)	Placebo shampoo and solution	After 6 m, impr. anagen/telogen rate for both shampoo (sh) and solution (so, p < 0.001). Efficacy ranking: sh + so> so > sh > placebo	moderate	[46]
Single-center, open-label, uncontrolled	5 M with AGA	Solution (leave-on) with MNX (10%), finasteride (0.1%), biotin (0.2%), caffeine citrate (0.05%)	None	After 6 m, assessment by a non-blinded expert: clinical improvements “visually noticeable” in all 5 patients. A blinded physician rated the overall effect as +0.75 in 1 P, +1.00 in 2 P, and +1.25 in a further 2 P on a scale where 0 means “no change”, +1—“slightly incr.”, and +2 “moderately incr”. After 180 d,100% of P satisfied with the treatment.	very low	[49]
Randomized, double-blind, controlled	16 M and 16 F with AGA	Marketed hair tonic (leave-on) with acetyl tetrapeptide-3, biochanin A (red clover extracts), P. ginseng extract, Salvia officinalis oil (undiscl. conc.)	3% MNX solution	Blinded experts’ assessment after 24 w: in the vertex area, hair status improved (from “slightly” to “greatly”) in 100% of participants in both I and C groups, “excellent improvement” in 12.5% of the I group and 21.0% of the C group (ns). In the frontal area, hair status improved in 87.5% of the I group and 85.0% of the C group (ns). Incr. in terminal hair count in both the I group (8.3%, p = 0.009) and the C group (8.7%, p = 0.002), no significant differences between groups. Increased HMI in both groups: I (13.8%, p = 0.008) and C (31.5%, p = 0.026) after 24 w, no difference between the two groups (p = 0.158).	moderate	[50]
Single-center, randomized, double-blind, controlled	24 M withAGA	Morning: 5% MNX lotion (leave-on) Evening: Lotion (leave-on) with R. officinalis, Olea europaea, lipidosterolic extract of S. serrulata (undiscl. conc.)	5% MNX lotion (morning and evening)	Hair diameter bigger in the I group than in the C group after 24 w (+19.0%, p = 0.005) and 36 w (23.9%, p = 0.001). No significant changes in hair density. PA score significantly lower (better outcome) in the I group than in the C group (for various questions, a decrease by 45.4% to 59.1%, p from 0.001 to 0.007).	moderate	[52]
Multicenter, open-label, observational	527 M and F with AGA	Marketed cosmetic solution (leave-on) with DPNO, arginine, 6-O glucose linoleate (SP94), piroctone olamine, Vichy mineralizing water (undiscl. conc.)	None	After 3 m, 89.0% of P and 96.7% of treating dermatologists satisfied with the product.	very low	[47]
Two-center, open, randomized, controlled	100 F with positive pull test (TE)	Marketed hair lotion (leave-on) with acetyl tetrapeptite-2, biotin, creatine, panthenol, pyridoxine HCl (undiscl. conc.) + marketed neutral shampoo (rinse-off)	Marketed neutral shampoo only	After 8 w, the decr. in density of telogen hairs was higher in the intervention group than in controls (p = 0.046). Reduction in the total number of hairs shed in 60 s was larger in the I group than in the C group after 8 w (−31.8% vs. −13.5%, p= 0.039) and 16 w (−43.6% vs. −33.1%, p = 0.058). No significant difference in Anagen/Telogen Ratio between the I group and the C group (p = 0.320).	low	[66]
Randomized, controlled, double-blind	62 M with AGA	Foam (leave-on) with polyphenols (DHQG and EGCG2), NHE, zinc salt (anion unspecified), glycine, caffeine (undiscl. conc.)	Vehicle	After 3 and 6 m: stronger decrease in telogen rate in the I group than in the C group (p = 0.02). Increase in hair density observed in both the I group (p = 0.001) and the C group (p = 0.04). No significant differences between I and C.	Moderate	[65]
Single-center, open-label, uncontrolled	150 P with AGA (60 M and 90 W)	Marketed serum (leave-on) in a roller with caffeine, S. serrulata, and 25 other ingredients (undiscl. conc.)	None	After 8 w, incr. thickness and density of crown and vertex hair (p < 0.05), no significant changes in frontal hair. P satisfaction rates in various aspects of hair growth between 80 and 100%, except hair length (40%).	very low	[58]
Single-center, open-label, uncontrolled	32 M and F with hair loss or alopecia	Marketed hair serum (leave-on) with P. amygdalus dulcis oil, hydrolyzed wheat protein, hydrolyzed soy protein, caffeine, arginine, R. officinalis leaf oil, and 17 other ingredients (undiscl. conc.)	none	Incr. hair growth rate after 30 d (+10.5%, p < 0.01) and 60 d (+31.6%, p < 0.01). Incr. hair thickness after 30 d (+24%, p < 0.01) and 60 d (+34%, p < 0.01). Incr. hair density after 30 d (+25%, p < 0.01) and 60 d (+40%, p < 0.01).	very low	[68]
Single-center, open-label, uncontrolled	20 M with AGA	Liquid (leave-on) with Procapil™ 3% 3, caffeine (undiscl. conc.), zinc PCA 4 (undiscl. conc.)	None	After 12 w: a 26.9% decrease in hair loss (p = 0.026), a 53% increase in terminal/vellus hair ratio (p = 0.028), and no significant changes in anagen rate and density. IA: improvement (slight to much) in 68.4% of P.	very low	[59]
Single-center, randomized, placebo-controlled, double-blind	46 P with AGA (27 M and 19 W)	Solution “APN” (leave-on) with adenosine (0.75%), panthenol (1%), niacinamide (2%)	Solution with MNX 5%	After 4 m, incr. in hair density (I group: +6.2%, p < 0.001; C group: +5.0%, p < 0.01) and hair thickness (I: +10.3%, p < 0.001; C: +5.1%, p < 0.001). No direct comparisons of I vs. C.	low	[64]
Single-center, randomized, placebo-controlled, single-blind	84 M and F with self-perceived “thinning hair”	Shampoo (rinse-off) with caffeine (0.4%) and adenosine (0.2%)	Placebo shampoo	After 3 m, hair density incr. by 10.2%, hair loss decr. by 35.5% (each p < 0.001 as compared with baseline and the C group).	low	[70]

Abbreviations: AGA—androgenic alopecia; C—comparator/control (placebo, sham treatment); d—days; DHQG—dihydroquercetin-glycoside; DPNO—2,4-diamino-pyrimidine-N-oxide, EGCG2—epigallocatechingallate-glucoside 2; F—female(s); I—intervention (verum, test treatment); IA—investigator’s assessment; incr.—increase(d); decr.—decrease(d); HCD index—hair cycle disturbance index; HMI—hair mass index; impr.—improved/improvement; M—male(s); MNX—minoxidil; m—month(s); NHE—nicotinic acid hexyl ester; ns—nonsignificant; P—participant(s); PA—participant’s assessment; sign.—significant(ly); TE—telogen effluvium; undiscl. conc.—undisclosed concentration(s); w—week(s). ¹ The ingredient hidden under the acronym HUCP was not disclosed by the authors of the source paper. In the context of hair loss products, Sawaya and Shapiro used it for hyaluronic acid [73], and no other uses or explanation could be found in the indexed literature or PubChem. ² Article [44] presents data from 4 separate trials. ³ Procapil™—a proprietary complex of oleanolic acid, apigenin, and biotinoyl tripeptide-1. ⁴ Zinc PCA—a complex of one zinc anion and two molecules of pyrrolidone carboxylic acid (PCA).

.

Looking at the formulations of topical products tested in all 41 included trials of topical anti-hair loss preparations (as listed in Table 4, Table 5 and Table 6), there were 27 “leave-on” topical products (lotions, solutions, extracts, serums, or fluids; 79.4%) and 7 “rinse-off” topical products (shampoos; 20.6%). Two studies tested two products in one trial: shampoo and solution [46] and serum and shampoo [53]. The shortest study lasted 1 month [72], and the longest 18 months [51]. The total number of subjects participating in the analyzed studies was 4065, of which 1802 (44.3%) were men, 1546 (38.0%) women, and 717 (17.6%) were mixed groups with an undisclosed sex ratio. The age range in the studies was 18 to 75 years. The strength of evidence according to the GRADE methodology was assessed as very low in 20 studies (51.2%), low in 10 (24.4%), and moderate in the remaining 10 (24.4%). The presence or absence of an appropriate comparator had a significant impact on the assessment of the strength of evidence provided in the analyzed trials. Further factors that reduced the assessment were a lack of blinding, non-validated or error-prone outcome measurements, a lack of information on the concentration of the tested substance, testing a mixture of substances considered to be active, a small sample size, and a short follow-up period.

Other than the four ingredients tested in dedicated clinical trials (adenosine, caffeine, melatonin, and placental proteins) and the twelve substances tested only as ingredients of complex mixtures, or the remaining twenty (55.6%) ingredients advertised in trichological shampoos as “active” (Table 1), no clinical trials of efficacy were retrieved in the present literature query.

4. Discussion

The present analysis demonstrates that, among numerous ingredients of trichological shampoos advertised as “active against hair loss”, clinical evidence of varying strength is only available for adenosine, caffeine, placental proteins, and melatonin. The mechanisms of action of the first three substances were discussed in detail in our previous articles [14,41,74]. Therefore, in this paragraph, we provide only the key facts. Adenosine is a pivotal molecule for most fundamental biological processes, such as energy transfer by adenosine triphosphate (ATP) and adenosine diphosphate (ADP), signal transduction by cyclic adenosine monophosphate (cAMP), inositol triphosphate (IP3), and IP3/diacylglycerol via the G-protein-coupled adenosine receptors A₁, A_2A, A_2B, and A₃. Stimulation of the A_2B receptor increases cellular cAMP levels, FGF-7 expression, and activation of the Wnt/β-catenin pathway, leading to increased expression of genes regulating cell proliferation in the hair unit [18]. Adenosine stimulates dermal papilla cell proliferation and epithelial cell differentiation in the hair bulb and increases blood flow around the hair unit, which is crucial for the induction and maintenance of hair growth. Adenosine induces and prolongs the anagen phase, thereby accelerating hair growth. The therapeutic effects of minoxidil against hair loss are mediated by adenosine A₁ and A₂ receptors [18]. Caffeine is an adenosine receptor agonist with biological effects similar to adenosine [14]. Furthermore, it acts as a phosphodiesterase inhibitor, preventing the breakdown of cyclic adenosine monophosphate (cAMP) in cells. Caffeine also has antioxidant properties and may counteract oxidative stress that damages the hair unit. It also increases the expression of insulin-like growth factor 1 (IGF-1), which initiates and maintains the anagen phase [74]. The biological effects of placenta depend on the degree of processing. Fresh human placenta has the strongest stimulating effect due to its high content of active hormones, growth factors, proenzymes and enzymes, transport and storage proteins, structural proteins, and nutrients. Human placenta in various forms is available to consumers in Japan, China, Singapore, and India. In the EU and USA, the use of human cells and tissues, including placenta, in cosmetic products is prohibited due to concerns about transmissible diseases. Animal placenta for cosmetic applications has to be processed in order to remove or inactivate biologically active molecules in order to be classified as a cosmetic ingredient rather than a medicinal product. In such a processed form, only hair or skin-conditioning functions are ascribed to placenta proteins and placenta protein hydrolysates [41]. Melatonin regulates a range of physiological processes, including the regulation of the circannual and circadian cycles, as well as aging. In the context of the physiology and pathology of the hair unit, melatonin’s potent antioxidant and antiapoptotic properties seem pivotal to its beneficial effects [44].

In the cosmetic industry and cosmetic marketing, advertisers draw on common assumptions about science to present skin-care products as “scientific” or “science-based” [75]. The use of scientific terms associated with objective knowledge and the impartiality of science is used to overcome the common consumer skepticism toward advertising by creating a sense of credibility and “transparency” on product ingredients and their benefits [76,77,78]. The scientific jargon used in marketing lacks explanation, but at the same time science is employed to explain phenomena beyond its explanatory powers, such as beauty standards [79]. This practice is referred to as “science-washing”, defined as the use of science beyond what evidence shows, without appropriate credentials or in instances where science cannot give the answer [80]. This term, which accurately indicates the dependence of marketing disinformation on scientific authority, is currently encountered in public discourse, rather than peer-reviewed scientific literature [81,82]. Science-washing effectively distorts our understanding of scientific terms and reduces the role of science to a menial, commercial function. This tendency manifests in the marketing use of terms like “cosmeceuticals”, “dermocosmetics”, or “hypoallergenic” products, which were initially proposed by scientists in the pursuit of more effective and safer cosmetics, but were later effectively incorporated into marketing vocabulary [83,84,85,86,87]. Recommendations of cosmetic products by medical associations or scientific institutions may be perceived as another form of “science-washing” [88,89]. Another related and partly overlapping term, “scienceploitation”, is used mainly in reference to unethical practices of offering seemingly science-based but not validated and not approved therapy methods like stem cell treatments [90,91,92]. In contrast to these “scientific-turned-marketing” terms, the words “trichology” and “trichological” seem to have gone down the reverse, “marketing-turned-scientific”, path: as already discussed in the introduction, these terms were coined in the commercial context and only later entered mainstream scientific terminology, without actually ever leaving the realm of marketing.

The overall impression from the present study is that the majority of substances added as “active ingredients” to topical trichological products actually have no scientific backing. At present, only four (adenosine, caffeine, placental proteins, and melatonin) have been individually studied in dedicated clinical trials, though the resulting evidence is mostly of low strength due to flaws in study design and size. Moreover, for two advertised “active ingredients” of trichological shampoos in Table 1 (niacinamide and Zingiber officinale), there is evidence speaking against their beneficial effects, which will be discussed in detail below. Twelve ingredients were only tested in clinical trials as components in complex products combining various substances presumed to be beneficial to hair (Table 6). This was the case for A. millefolium extract, arginine, biotin, hydrolyzed wheat protein, hydrolyzed soy protein, P. ginseng extract, panthenol, piroctone olamine, P. amygdalus dulcis oil, R. officinalis, S. serrulata, and U. dioica. Regardless of the questionable strength of scientific evidence in most of these studies, such a study design in no way authorizes drawing any conclusions about individual effects of these ingredients on hair. To illustrate this, let us imagine a hypothetical shampoo “XYZ” with ingredients X, Y, and Z, of which ingredient X will have an unfavorable effect on hair, ingredient Y will have a beneficial effect much stronger than the untoward effect of X, and ingredient Z will be neutral. In a clinical trial, the overall effect of the imaginary product “XYZ” would prove beneficial, owing to the strong activity of ingredient Y, while X would lessen the net effect and Z would constitute an unnecessary ballast. Therefore, an assumption that the efficacy of the shampoo “XYZ” is a proof of the effectiveness of each ingredient X, Y, and Z will amount to the form of faulty reasoning referred to as the fallacy of division, which is also known as the “whole-to-part fallacy” [93]. The fallacy of division occurs when, from an observed property of an entire item (here: a complex topical trichological product), one infers that the same property is attributable to each of its parts (here: ingredients) [94]. Arguably, some ingredients must be active if beneficial effects of a complex product are confirmed in well-designed, controlled trials. However, the actual effect of each ingredient, whether beneficial, neutral, or detrimental, will remain obscure until separately tested in a randomized, controlled trial against a suitable placebo. It must be stressed, therefore, that the information collated in Table 6 should by no means be regarded as a proof of efficacy of any of the ingredients listed. The table was created merely in order to document the search process as well as map the gaps in the current state of knowledge.

For the remaining 20 (55.6%) ingredients declared as “active” in analyzed trichological shampoos, their activity was not studied in any published clinical trials, not even as parts in complex products. This observation largely confirms our concerns stemming from the study of 92 products—shampoos, mesotherapy solutions, lotions, serums, and conditioners of predominantly international brands—available in Poland between 2018 and 2019. In that study, we found that, among 448 unique ingredients listed in the products, 207 were advertised as “active” against hair loss in at least one of them [39]. At that time, scientific evidence of varying (predominantly very low) quality could be found in the medical literature for just eight (3.9%) of these ingredients. Only 38.0% of the products contained at least one ingredient with confirmed beneficial effects on hair, including 8.7% containing two such ingredients. The majority of the topical trichological products (62.0%) analyzed in that study would not contain any ingredient with a confirmed influence on hair growth, either beneficial or detrimental. Interestingly, ingredients supported with available evidence were not at all the most widespread ones in the analyzed products. We also found that, according to the evidence available at the time of the study, some ingredients advertised as “active” could actually worsen hair condition [39]. For example, 6-gingerol—the major active constituent of ginger (Z. officinale)—was demonstrated to cause a dose-dependent inhibition of hair growth in ex vivo cultures of human hair units [95], as well as in an in vivo mouse model [96]. In spite of this evidence, Z. officinale was present on ingredient lists of 4 out of 92 topical trichological products (4,3%), including three scalp mesotherapy solutions and one lotion—in all of them, ginger was promoted as “beneficial for hair” [39]. Fortunately, we did not find Z. officinale in the ingredient lists of any of the trichological shampoos analyzed in the first study and in our follow-up evaluation of trichological shampoos available on the market from February 2022 to May 2023 [40], and it was also not found in the present analysis.

A closer look at niacinamide offers an interesting, multi-dimensional insight into the interaction between published scientific evidence and the composition of topical trichological products. The period 2015–2020 may arguably be considered as formative for the perception of niacinamide. A literature query combining the term “hair” with “niacinamide”, “nicotinamide”, or “vitamin B3” revealed that all relevant original research on the influence of topical niacinamide on hair appeared in the indexed literature between 2015 and 2020. During that period, the first three original studies were published of the effect of niacinamide on hair growth [62,97,98]. Other than that, by the time of completing the present review, only one further experimental paper was published with indirect relevance to the topic, and four clinical trials of complex products with niacinamide, where it was impossible to single out its individual influence on hair. The first of the three relevant studies was a double-blind, randomized clinical trial of Japanese men with AGA, in which participants were treated with lotions containing either adenosine 0.75% or niacinamide 0.1% [62]. The authors stated explicitly that they did not consider niacinamide to be a hair growth promoter and used it as a “placebo-like lotion” because they did not receive clearance for a placebo-controlled study. They reported significant improvements in both compared groups after 6 months of treatment in terms of an increase in thick hair ratio and a decrease in vellus (thin) hair ratio. Nevertheless, the increase in objectively measured hair diameter, as well as the percentage of patients who noticed increased thickness of hair, was significantly higher in the adenosine group. No significant change in hair density was observed in either group, with a tendency toward an increase seen in the adenosine group (p = 0.097), but not in the niacinamide group (p = 0.554) [62]. Altogether, these results seem to speak in favor of adenosine, rather than niacinamide, as the hair-growth-promoting agent. Unfortunately, the lack of a placebo in this study did not allow the authors to compensate for bias, including seasonal changes in hair growth and loss [14]. The second study relevant to the topic, published in 2018, demonstrated inhibitory effects of niacinamide in ex vivo human hair follicles [97]. Two years later, Oblong et al. thoroughly compiled existing evidence to conclude that niacinamide actually has a net neutral effect on human hair growth [98]. This led us to consider niacinamide as equivalent to a placebo in our previous paper [18]. The last, so far, study of niacinamide was conducted in cultured human dermal papilla cells—specialized mesenchymal cells at the base of the hair follicle that are crucial for hair growth and pigmentation but are not hair cells themselves [99]. Moreover, the authors measured markers of oxidative stress, rather than proliferation or growth, and only speculatively suggested that “niacinamide could enhance hair growth by preventing oxidative stress-induced cell senescence and premature catagen entry of hair follicles”. Beyond that, four trials were published: two randomized, double-blind studies and two open-label studies of complex products that consisted of three to six presumably “active” ingredients—a design rendering it impossible to single out and assess the actual effect of niacinamide [64,100,101,102]. Collectively, the above research seemed to indicate that niacinamide has either a neutral or an unfavorable effect on hair growth.

Expectedly, published research results questioning the supposed beneficial effects of niacinamide on hair should be noticed and addressed accordingly by manufacturers of topical trichological products that are promoted as “science-based”. Taking into account the lag between product design and emergence on the market, we propose to consider the data from the previous study of 2018–2019 as representative of the “before evidence” period with regard to niacinamide effects on hair [39] and the study of 2024 as representative of the “after evidence” period [40]. Comparison of the data from these studies suggests that there was indeed a change in the usage of niacinamide: In the analysis of topical trichological products available between October 2018 and August 2019 [39], niacinamide was present in 9 out of 31 (29.0%) trichological shampoos, including 5 (16.1%) in which it was declared as an “active ingredient”. In the latter analysis, niacinamide was listed in only 1 of 43 (2.3%) trichological shampoos available in 2024 [41]. This single shampoo, in which niacinamide was both present and pronounced as an “active ingredient”, was launched after completion of the first study, i.e., after August 2019, apparently in spite of the already published report suggesting unfavorable effects of niacinamide on hair growth [97]. Nevertheless, within the 5-year span between both studies, the overall presence of niacinamide in trichological shampoos on the market decreased significantly from 29.0% to 2.3% (chi² test, Yates’ p = 0.02). Altogether, this might be cautiously interpreted as a sign that most manufacturers of trichological shampoos follow the medical literature and abandon ingredients when scientific evidence speaks against them. Unfortunately, another observation from the current scoping review is that the lack of positive evidence does not discourage them from using untested ingredients and declaring them as “active”. This was true in the case of the majority (20 out of 36) of ingredients included in the present analysis.

Another problem with the alleged science-based composition of trichological shampoos is illustrated by the case of Curcuma (turmeric): As of May 2025, the “Plants of the World Online” database listed 237 entries for the genus Curcuma, including 183 accepted species [103]. The species arguably best known to the general public is C. longa, which is the source of yellow turmeric—a spice with a myriad of health benefits ascribed to it, many confirmed scientifically [104,105,106,107,108,109,110]. Notably, no study of the influence of C. longa on hair has been published to date. Another species from the genus—C. aeruginosa—was demonstrated to inhibit testosterone 5α-reductase in experimental settings and proved effective against androgenetic alopecia in a randomized, double-blind clinical trial [111,112,113]. However, this picture is not entirely clear, as another randomized, double-blind trial showed that C. aeruginosa effectively inhibits the growth of axillary hair [114]. It remains unclear whether this difference is due to different hair types (scalp versus axillary), different fractions of the plant material used (root aqueous extract versus root oil), or other factors. Nevertheless, among the anti-hair loss products analyzed in the previous study, three (mesotherapy solutions and a topical lotion) included yet another Curcuma species—white turmeric (C. zedoaria)—that was declared as “active” in two of these [39]. For this particular species, there is no evidence published at present that would support the alleged beneficial influence on the hair, beyond an anecdotal mention of C. zedoaria use traditional in hair oils [115]. Even in the case of the “right” Curcuma species, there is still a question about the originality, quality, purity, and safety of the raw material used [116]. Nevertheless, for the average consumer who usually only knows that “turmeric is good for health”, information about the presence of turmeric in a product would probably be a sufficient incentive to purchase, without realizing the multitude and diversity of plant species hidden under the names “Curcuma” and “turmeric” and the problem of raw material quality. This story may be viewed either as another example of the division fallacy in the realm of topical trichological products or as another example of “science-washing”.

As mentioned above, the overall strength of evidence in the trials included in the present review was low. Many of these trials showed flaws in study design, including selection bias, a lack of adequate controls, and a lack of compensation for seasonal hair loss, as discussed in detail in our previous two papers [14,18]. Guyatt et al. suggested that publication bias should especially be suspected when the available evidence comes from a number of small studies, most of which have been commercially funded [117]. When looking at the trials on topical hair loss products, this might indeed be the case. Out of eleven trials of individual ingredients:

• In only two studies, the authors explicitly declared the absence of conflicts of interest (COIs) both with regard to the funding of the study and financial relations between authors with potentially commercial beneficiaries, of which a non-proprietary, in-house preparation was used in one study [72] and a commercial brand of product was named in the other [54].
• Six trials were disclosed (sometimes vaguely or indirectly) as industry-funded or -sponsored [45,55,56,57,61,62]. Except for the above-mentioned two studies, in the remaining three trials there was no statement in this regard.
• In five trials, at least some of the co-authors were disclosed as employees of manufacturers of products tested or received other financial gratifications from them for performing the study [45,55,61,62,69]. In two trials, the authors declared the absence of any link to manufacturers [54,72], while there was no statement in this regard in the remaining four [56,57,60,67].
• Tested products were identified by brand or trade name in five trials [54,55,56,57,67], non-proprietary, in-house preparations were described in three trials [45,60,72], and no statement was provided in the remaining three [61,62,69].
• Possible bias or study limitations were addressed in only two of the eleven trials [54,55].

Industry involvement in research does not automatically imply bad science. Collaboration between academia and industry is fundamental to technological progress [118,119]. On the other hand, the overlapping areas of clinical research, industry, and marketing seem to open the door to the specific type of bias referred to as “sponsorship bias”. Steel defines sponsorship bias as a situation when the financial interests of funders of scientific research influence claims made by scientists, especially in peer-reviewed publications. He pointed out that such claims are not necessarily false but may encourage recipients to infer false conclusions [120]. Sponsorship bias seems instrumental to science-washing. This phenomenon is not limited to hair care products, as it also affects regulated products, such as medicines, dietary supplements, or food for special medical purposes [121,122,123,124].

Next to research reports published in peer-reviewed journals, evidence can be found in other sources, e.g., academic theses and dissertations, research and committee reports, government reports, conference papers, and reports from ongoing research—information sources referred to collectively as “gray literature” [125,126]. Gray literature may reveal important details about topics that would otherwise be missed [127]. With a steady increase in information posted online, traditional systematic literature reviews could be combined with reviews of gray literature into “multivocal literature reviews” [128]. We abstained from relying on gray literature in our research, as the realm of topical trichological products seems especially prone to various kinds of bias with commercial claims oftentimes disguised as “scientific evidence”. This problem seems confirmed by the overall low quality of the analyzed peer-reviewed publications. We reasoned that the gray literature in this area might be even less trustworthy and would add to the uncertainty of the results. Therefore, we decided to confine our sources of data to full trial reports published in peer-reviewed journals, considering the peer-review process by independent referees as a means of providing a minimum of scientific quality and integrity. Moreover, a more detailed reporting of trial design enabled us to assess the strength of evidence provided in the trial reports. Assessing the strength of evidence according to GRADE is typical of systematic, rather than scoping, reviews. In fact, the present article was initially intended as a systematic review, closing a four-piece series of systematic reviews. In the process of writing, however, we have realized that the multitude of supposedly active substances covered, the heterogeneity in trial design and reported outcomes, as well as the numerous knowledge gaps would not allow us to register and complete this study as a systematic review. Instead, it seemed more reasonable and appropriate to register and finalize the present paper as scoping review. Due to the sheer volume of retrieved information, three active ingredients with sufficient data from published trials—adenosine, caffeine, and placental proteins—were presented in separate systematic reviews [14,18,41]. The present article concludes the series and offers an inventory of the many unknowns in the field of topical prescription-free treatments for hair loss.

5. Conclusions

Of the plethora of topical agents allegedly active against hair loss, only four have actually been tested in dedicated clinical trials: adenosine (four trials), caffeine (four trials), placenta proteins (four trials), and melatonin (one trial). The majority of these trials seem flawed in design and susceptible to bias and the strength of evidence delivered by them is predominantly low. Furthermore, a dozen ingredients with alleged efficacy against hair loss were only tested clinically as part of complex products, which makes it impossible to draw any conclusion about each such ingredient individually. Even more worryingly, a substantial majority of topical ingredients promoted as active against hair loss were never actually tested clinically in this regard. We conclude, therefore, that there are major gaps to be filled in the field of non-prescription treatments for hair loss, while unsubstantiated claims of supposed beneficial properties often refer to alleged scientific evidence.