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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 14
| Issue : 2 | Page : 49-54 |
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Targeted nutritional supplementation for telogen effluvium: Multicenter study on efficacy of a hydrolyzed collagen, vitamin., and mineral-based induction and maintenance treatment
Eva Maria Arias1, Nuria Floriach1, Gerardo Moreno-Arias2, Alejandro Camps2, Salvador Arias3, Ralph Michel Trüeb4
1 R&D Department, Laboratorio Genové, Sant Llorenç d'Hortons, Spain
2 Department of Dermatology, Centro Médico Teknon, Barcelona, Spain
3 Department of Dermatology, Hospital Universitario Virgen de las Nieves, Granada, Spain
4 Centre for Dermatology and Hair Diseases Professor Trüeb, Zurich-Wallisellen, Switzerland
| Date of Submission | 18-May-2021 |
| Date of Acceptance | 30-Oct-2021 |
| Date of Web Publication | 04-Apr-2022 |
Correspondence Address:
Ralph Michel Trüeb
Center for Dermatology and Hair Diseases Professor Trüeb, Bahnhofplatz 1A, CH-8304 Wallisellen
Switzerland
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijt.ijt_57_21
 Abstract | | |
Background: The condition of the hair is closely related to the nutritional state. Normal supply, uptake, and transport of nutrients are of fundamental importance in tissues with a high biosynthetic activity such as the hair follicle. Objective: The objective of the study was to evaluate the efficacy of a nutritional-based induction and maintenance treatment for telogen effluvium formulated with a combination of hydrolyzed collagen, amino acids, vitamins, and minerals. Patients and Methods: The clinical studies were conducted with each nutritional treatment individually, and both in sequential combination. Anagen/telogen ratio, hair density, and tolerability of treatment were assessed at baseline, 4 weeks of induction therapy, and another 12 weeks of maintenance treatment. Trichogram results showed a significant improvement of the anagen/telogen ratio between baseline and final visit at 16 weeks, with an increase of hair in anagen and a reduction of hair in telogen. Furthermore, a significant increase was observed in hair density. The effect size of the combination treatment was higher than that of each of the two products used separately as monotherapy. Conclusions: The study results provide a proof of concept for targeted nutritional supplementation for the treatment of telogen effluvium, with a special emphasis on the role of collagen, besides specific amino acids, vitamins, and minerals.
Keywords: Alopecia, collagen, hair cycle, hair loss, nutritional supplements, telogen effluvium
How to cite this article:
Arias EM, Floriach N, Moreno-Arias G, Camps A, Arias S, Trüeb RM. Targeted nutritional supplementation for telogen effluvium: Multicenter study on efficacy of a hydrolyzed collagen, vitamin., and mineral-based induction and maintenance treatment. Int J Trichol 2022;14:49-54 |
How to cite this URL:
Arias EM, Floriach N, Moreno-Arias G, Camps A, Arias S, Trüeb RM. Targeted nutritional supplementation for telogen effluvium: Multicenter study on efficacy of a hydrolyzed collagen, vitamin., and mineral-based induction and maintenance treatment. Int J Trichol [serial online] 2022 [cited 2023 Jun 1];14:49-54. Available from: https://www.ijtrichology.com/text.asp?2022/14/2/49/342546 |
| Introduction | |  |
The quantity and quality of the hair are closely related to the nutritional state of an individual. Normal supply, uptake, and transport of proteins, calories, trace elements, and vitamins are of fundamental importance in tissues with a high biosynthetic activity such as the hair follicle. Since the hair shaft is composed almost entirely of protein, protein is critical for the production of normal healthy hair. The rate of mitosis is sensitive to the calorific value of diet, provided mainly by carbohydrates. Finally, a sufficient supply of vitamins and trace metals is essential for the biosynthetic and energetic metabolism of the follicle.
And yet, there is hardly another field with so much prejudice, misconception, and debate as nutritional supplementation therapy and hair health. A central question that arises is whether increasing the content of a seemingly adequate diet with specific amino acids, vitamins, and/or trace elements may further promote hair growth and quality. It is generally believed that unless hair loss is due to a specific nutritional deficiency, there is only so much that nutritional therapies can do to enhance hair growth and quality. Nonetheless, there are a number of factors, such as life cycle needs, dietary habits, lifestyle, environmental toxins, age, and co-morbidities, that may influence hair health to such a degree that it can be expected that a nutritional therapy can boost hair that is suffering from these issues.
The normal hair cycle lasts between 3 and 5 years,[1] with a normal shedding of between 50 and 100 hairs per day, depending on the age, sex, amount of hair, seasonal, and hormonal factors.[2] Typically, 85%–90% of the hair on the scalp is actively growing during the anagen phase of the hair cycle, while a maximum of 15% are in the resting or telogen phase of the cycle, before eventually being shed in exogen.
Many factors may lead to a pathologically increased hair loss. Whatever the cause, the follicle tends to behave in a similar way. Studies on the dynamics of the follicular cycle have originally depended on the microscopic evaluation of plucked hairs with quantitative measuring of the number of individual hair roots (trichogram).[3] Today, the objective of trichogram measurements is to evaluate and count the status of individual hair roots and to establish the ratio of anagen to telogen roots.
Telogen effluvium is the most common cause of hair loss and results from an increase in the percentage of follicles in telogen >20%, resulting in an increased shedding of telogen hairs. In the original description of Kligman,[4] telogen effluvium is an acute diffuse hair loss brought about by a variety of triggers. However, the acuity and degree of telogen effluvium will depend on the severity and the time of exposure to the causative event.[5],[6] Besides acute telogen effluvium, clinical experience proves that chronic telogen effluvium also exists, which is arbitrarily defined as diffuse telogen hair loss persisting longer than 6 months. It either represents a primary disorder of synchronization, or it is secondary to a variety of identifiable systemic disorders, such as iron deficiency, thyroid disease, dietary habits, and drugs. The cause of chronic telogen effluvium may be multifactorial and is often difficult to establish.
The objective of the present study was to evaluate the efficacy of a nutritional-based induction therapy followed by maintenance treatment formulated with a combination of hydrolyzed collagen, amino acids (L-cystine, L-methionine), vitamins (of the B group), and minerals (iron, zinc, and selenium) for telogen effluvium.
| Patients and Methods | | |
Women and men aged between 18 and 75 years with telogen effluvium were initially recruited for the pilot study with the drinkable solution of hydrolyzed collagen (8 g), calcium pantothenate (Vitamin B5), pyridoxine hydrochloride (Vitamin B6), and zinc sulfate for induction therapy.
Test persons who were informed on the study design and product and agreed to participate by signing a respective informed consent sheet were administered sachets composed of hydrolyzed collagen (8 g), calcium pantothenate (Vitamin B5), pyridoxine hydrochloride (Vitamin B6), and zinc sulfate (marketed as Pilopeptan Intensive® or Trichosense Intensive®) for 1 month in a single-center, open, uncontrolled study with the objective to evaluate the efficacy of the drinkable solution treatment of telogen effluvium. The study was carried out in Spain at the Centro Dermatológico Estético Alicante.
Exclusion criteria were clinical and/or biological signs of hyperandrogenism in women (hirsutism, hyperseborrhea, severe acne, and polycystic ovary syndrome) or use of hormonal treatments with pro-androgenic activity in women, systemic diseases (diabetes, arterial hypertension, severe ischemic heart disease, collagen vascular diseases, neoplastic disease, anaemia, metabolic diseases, chronic inflammatory bowel disease, nutritional deficiencies, and hypocaloric diet), pathologies on the scalp (psoriasis and dermatitis), drugs known to cause hair loss (fluoxetine, anticoagulants, retinoids, and others), history of serious injuries or surgical interventions under general anesthesia preceding 3 months, pregnancy, use of other specific treatments (topical minoxidil and aminexil, finasteride, or oral antiandrogens), or participation in any other therapeutic efficacy protocol for hair in the last 3 months, and noncompliance, that is, nonattendance to follow-up visits, or interference of lifestyle with compliance with the protocol.
Three control visits were established, at the beginning of the study (T0), 15 days from the start of the study, and another 15 day from the second visit, as the endpoint (T15 and T30). The variables evaluated were the percentage of hair follicles in anagen and telogen phase at T0 and T30.
Evaluation by the researcher from the global photographs of the patient's scalp, percentage of hair in anagen and telogen phase at the baseline visit and at the end of the study, and the number and type of adverse reactions related to the use of oral treatment were determined to assess the tolerance of the product at visits T15 and T30. Hair-quality evaluation was determined by means of the improvement in the appearance of the hair related to hair loss reduction effect, hair quantity, hair thickness/volume, hair resistance, overall treatment satisfaction, shine, softness, volume, and hair appearance.
A single-center, randomized, placebo-controlled, double-blind study was then performed with the purpose to investigate the effect of the nutritional supplement in tablet form (marketed as Pilopeptan Woman® or Trichosense Woman®) on the improvement of telogen effluvium. Two intervention groups were established that included 25 volunteers randomized into each group. One group took tablets with the active ingredients, composed of hydrolyzed collagen (300 mg), thiamine hydrochloride (Vitamin B1), riboflavin (Vitamin B2), nicotinamide (Vitamin B3) calcium pantothenate (vitamin B5), pyridoxine hydrochloride (Vitamin B6), Vitamin B7 (biotin), folic acid (Vitamin B9), L-cystine (100 mg), L-methionine (50 mg), ferric pyrophosphate, zinc sulfate, sodium selenite, and hyaluronic acid as sodium salt (10 mg), while the other group received placebo, to be taken as one tablet daily for 5 months.
All volunteers received a detailed explanation of the study and written informed consent. The inclusion criteria were women in otherwise good health with telogen effluvium and an anagen/telogen ratio <4, who had signed the written consent and were informed of the objective of the study, sufficient motivation, and time availability. Exclusion criteria were the same as in the first study.
Three control visits were stablished at baseline point (T0), after 90 months (T90), and at the end of the study (T150). Global photographic assessment and photomicrographs of the scalp were performed, besides the trichogram and phototrichogram with the TricoScan® technique, at baseline visit and at the end of the study. Subjective parameters were also evaluated comparing the observations at the beginning of the study with the endpoint to asses if those parameters were improved.
The study was evaluated and approved by the Ethics Committee of Quirónsalud Hospital group in Barcelona.
Finally, for the sequential combination of both nutritional supplements, a multicenter, open-label, uncontrolled study was performed with the objective to determine the effectiveness of a combined induction and maintenance therapy in women with telogen effluvium.
The inclusion criteria were otherwise healthy women over the age of 18 years diagnosed with telogen effluvium with an anagen/telogen ratio ≤4. The exclusion criteria were the same as in the former studies.
Test persons were administered the drinkable solution in the first 1 month, followed by tablets for another 3 months.
Three control visits were stablished at the beginning of the study (T0) in which the baseline diagnostics were assessed, control visits at 4 weeks after starting the treatment (T30), and the final visit (T120). The main variables analyzed in the study were again the percentage of hair in anagen and telogen, obtained with the trichogram at T0 and T120. Subjective parameters were evaluated to determine whether volunteers observed any difference during the study.
Again, the protocol and all study materials were approved by the Ethics Committee of Quirónsalud Hospital group in Barcelona. The study was multicentric and carried out in different hospitals and medical centers in Spain by 20 researchers.
| Statistics | | |
The percentage of hair in anagen and telogen phase between the three treatments was compared by parametric assay, one-way ANOVA test. Differences between the initial values and the endpoint values of the percentage of hair in anagen and telogen phase for each treatment were evaluated by a t-test. Statistical analysis was performed using the SPSS 26.0 statistical software (SPSS Inc., Chicago, IL, USA) and P < 0.05 was considered significant.
| Results | | |
A total of 50 participants (25 women and 25 men) were included in the pilot study with the liquid formulation with high-dose collagen (Pilopeptan Intensive®).
Again, a total of 50 women between the age 18 and 60 years were enrolled in the study with the tablets (Pilopeptan Woman®).
Finally, 160 women between ages 19 and 87 years were recruited in the combination therapy of liquid formulation (Pilopeptan Intensive®) followed by tablets (Pilopeptan Women®), with a total of 142 women completing the study.
The three groups of test persons in the consecutive studies with liquid formulation tablet formulation, and combination therapy, were selected to evaluate whether significant differences were observed with the nutritional supplements taken individually or in combination. The data analysis was done by comparing the values obtained at baseline with the results at the end of the studies. The results are expressed as mean and standard deviation of the percentage of hair in anagen phase and the percentage of hair in telogen phase, as shown in [Figure 1] and [Figure 2]. | Figure 1: Percentage of hairs in anagen phase from the baseline visit to the final visit comparison with Pilopeptan Intensive®, Pilopeptan Woman® tablet®, and the combination of both nutritional supplements. Brackets between bars of each treatment indicate significant differences between groups (P < 0.05, one-way ANOVA test)
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 | Figure 2: Percentage of hairs in telogen phase from the baseline visit to the final visit comparison with Pilopeptan Intensive®, Pilopeptan Woman® tablets, and the combination of both nutritional supplements. Brackets between bars of each treatment indicate significant differences between groups (P < 0.05, one-way ANOVA test)
Click here to view |
The results obtained show that the drinkable solution (Pilopeptan Intensive®) increased anagen percentage from baseline 67.92% ± 6.21% to 71.52% ± 6.27% (P < 0.05) at closeout, and with the tablets (Pilopeptan Woman®), improvement was observed from a percentage of hairs in anagen from 68.63% ± 4.72% to 75.68% ± 7.05% (P < 0.001) (normalization).
The highest increase in the percentage of hairs in anagen phase was observed with the sequential combination treatment (Pilopeptan Intensive® and Pilopeptan Woman®).
Regarding the improvement in anagen phase between each treatment [Figure 1], significant differences were observed between the combination treatment compared to individual treatments, with lower improvement.
The percentage of hairs in telogen a of the women groups of the three studies was also assessed. The results had shown that when the data were compared from the baseline visit to the end of the study (final visit) in the three studies, the number of hairs in telogen phase was reduced. The study with the drinkable solution showed an initial percentage of 19.96 ± 3.68 and 16.64% ± 3.17% (P < 0.05) at the end of the study. For the tablets study, the percentage of hairs in telogen phase was reduced from 31.38 ± 4.72 to 24.32 ± 7.06 (P < 0.001). The treatment of both nutritional supplements in combination with telogen effluvium showed the highest improvement with a reduction of the telogen phase [Figure 2] from 46.40% ± 21.50% to 23.82% ± 14.28% (P < 0.001). When the three treatment groups were compared, the results revealed that significant improvement with the combination treatment was obtained compared with the intake of the nutritional supplements individually.
These results suggest that women with telogen effluvium could significantly improve hair loss when the combination of the drinkable solution as induction treatment was followed by the tablets as a maintenance treatment.
Photographs of the scalp were obtained to evaluate the clinical improvement with the treatments. The images demonstrate the improvement both in the photomicrographs and global photographic assessment.
Hair density was also evaluated in the study with tablets and in the combination study. In both cases, significant improvement was observed. In addition to the assessment of the objective parameters, hair-quality evaluation was determined by means of the improvement in the appearance of the hair related to hair loss reduction effect, hair quantity, hair thickness/volume, hair resistance, overall treatment satisfaction, shine, softness, volume, and hair appearance. The comparison between the evaluation analyzed at the baseline visit with the results obtained at the end of the studies showed that the mean values collected from the volunteers were improved in the three studies performed.
| Discussion | | |
Since an important commercial interest lies in the nutritional value of various vitamin and amino acid supplements, a critical question that arises is whether increasing the content of an already adequate diet with specific amino acids, vitamins, and/or trace elements may further promote hair growth, specifically in women with telogen effluvium.
Protein is the main component of hair, with the primary component of the hair fiber being keratin, which is made from amino acids. The most abundant of these is cysteine which gives the hair fiber much of its strength through the linking of the sulfur in cysteine molecules of adjacent keratin proteins together in disulfide bonds. Meanwhile, the hair follicle exhibits a high rate of metabolism. As a group, B complex vitamins are important for metabolic functions and therefore required to utilize other nutrients such as carbohydrates and amino acids. Further insights into the role of oxidative stress open additional strategies for interventions into hair loss, since it has been shown that particularly in androgenetic alopecia, the hair papilla fibroblasts react more sensitive to oxidative stress.[7] Specifically, the body possesses endogenous defense mechanisms, such as antioxidative enzymes and nonenzymatic antioxidative molecules (glutathione and selenium), protecting it from free radicals.
Finally, the role of collagen in the aging of the hair follicle has just begun to be unraveled. Matsumura et al.[8] found that hair follicle stem cell aging results from proteolysis of type XVII collagen (COL17A1/BP180) by protease expression in response to DNA damage in stem cells and their commitment to epidermal differentiation. Meanwhile, the bioavailability of hydrolyzed collagen has been demonstrated in mice: orally administered 14C hydrolyzed collagen was digested and more than 90% absorbed within 6 h, with measurable accumulation in the skin.[9] A study in humans found hydrolyzed collagen absorbed as small peptides in the blood.[10] Ingestion of hydrolyzed collagen may affect the skin by increasing the density of collagen fibrils and fibroblasts, thereby stimulating collagen production.[11] It has been suggested, based on mouse and in vitro studies, that hydrolyzed collagen peptides have chemotactic properties on fibroblasts[12] or an influence on the growth of fibroblasts.[13]
The nutritional proposed in this study is based on an induction formulation with high-dose hydrolyzed collagen (8 g), Vitamins B5, B6, and zinc, and a maintenance formulation with lower-dose hydrolyzed collagen (300 mg), and added B complex vitamins, L-cystine, L-methionine, iron, selenium, and hyaluronic acid.
Anagen/telogen ratio, hair density, and tolerability of treatment were assessed at baseline, at 4 weeks of induction therapy, and another 12 weeks of maintenance therapy (16 weeks).
The trichogram results showed a significant improvement of the anagen/telogen ratio between baseline and the final visit at 16 weeks, with an increase of hair in anagen and a reduction of hair in telogen. In addition, a tendency toward increase of hair density and hair quality was observed between the respective visits.
The effect size of the combination treatment was higher than that of the use of each of the two products separately as monotherapy.
Low frequencies of adverse events due to treatment were recorded. Due to the once-a-day dosage, patient comfort and compliance were satisfactory.
| Conclusions | | |
The combination of an induction and a maintenance treatment based on nutritional supplements including hydrolyzed collagen, specific amino acids, vitamins, and minerals was effective in the following parameters studied: percentage of hair in anagen, percentage of hair in telogen, anagen/telogen ratio, and hair density. Better results were obtained with the sequential combination therapy compared to the individual nutritional supplements.
Academic medicine has notoriously resisted the concept that nutritional therapy might have health benefits of any significance. Part of this resistance arises from the fact that the potential benefits of nutritionals have been advocated by outsiders, who took their message directly to the public bypassing the establishment, and part from the fact that the concept of a deficiency disorder did not fit in well with the prevailing biomedical paradigms of disease.[14] The results of these studies provide a proof of concept for targeted nutritional supplementation for healthy hair based on knowledge of the physiology and biochemistry of hair growth and aging, with a special emphasis on the role of collagen, besides specific amino acids, vitamins, and minerals.
In summary, the clinical study data summarized above suggest that the specific hydrolyzed collagen-, amino acid-, vitamin-, and mineral-based nutritional treatment represent an effective induction and maintenance treatment option for women with telogen effluvium.
Financial support and sponsorship
Studies have been financed by Laboratorio Genove S. A.
Conflicts of interest
Trüeb RM performs consultant activities for Laboratorio Genove S. A. and Hans Karrer GmbH.
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| 4. | Kligman AM. Pathologic dynamics of human hair loss, I: Telogen effluvium. Arch Dermatol 1961;83:175-98. |
| 5. | Harrison S, Sinclair R. Telogen effluvium. Clin Exp Dermatol 2002;27:389-95. |
| 6. | Headington JT. Telogen effluvium. New concepts and review. Arch Dermatol 1993;129:356-63. |
| 7. | Bahta AW, Farjo N, Farjo B, Philpott MP. Premature senescence of balding dermal papilla cells in vitro is associated with p16(INK4a) expression. J Invest Dermatol 2008;128:1088-94. |
| 8. | Matsumura H, Mohri Y, Binh NT, Morinaga H, Fukuda M, Ito M, et al. Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis. Science 2016;351:aad4395. |
| 9. | Oesser S, Adam M, Babel W, Seifert J. Oral administration of 14C labelled gelatine hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57/BL). J Nutr 1999;129:1891-5. |
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| 11. | Matsuda N, Koyama Y, Hosaka Y, Ueda H, Watanabe T, Araya T, et al. Effects of ingestion of collagen peptide on collagen fibrils and glycosaminoglycans in the dermis. J Nutr Sci Vitaminol (Tokyo) 2006;52:211-5. |
| 12. | Postlethwaite AE, Seyer JM, Kang AH. Chemotactic attraction of human fibroblasts to type I, II, and III collagens and collagen-derived peptides. Proc Natl Acad Sci U S A 1978;75:871-5. |
| 13. | Shigemura Y, Iwai K, Morimatsu F, Iwamoto T, MoriT, Oda C, et al. Effect of prolyl-hydroxyproline (Pro-Hyp), a food-derived collagen peptide in human blood, on growth of fibroblasts from mouse skin. J Agric Food Chem 2009;57:444-9. |
| 14. | Goodwin JS, Tangum MR. Battling quackery: Attitudes about micronutrient supplements in American academic medicine. Arch Intern Med 1998;158:2187-91. |
[Figure 1], [Figure 2]
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