1. Research and Development Aripam Medical Center, Ashdod, Israel. Email: nadavpam@gmail.comnadavpam@gmail.com Research and Development Aripam Medical Center, Ashdod, Israel. Email: nadavpam@gmail.comnadavpam@gmail.com Medical evidences of the therapeutic effect of edible gelatin on telogen effluvium and androgenetic alopecia in both men and women Medical evidences of the therapeutic effect of edible gelatin on telogen effluvium and androgenetic alopecia in both men and women By Nadav Pam M.D.

2. Family: Married to Sara and father to Ori and Nadav. 1978: Graduated from the School of Medicine at the Technion, Haifa, Israel. 1979 – 1985: Medical doctor at I.D.F 1985 – 1990: Resident in the department of dermatology in Rambam hospital, Haifa. 1997: A member of the American Academy of Dermatology (AAD). 1991- 2013: Chief executive officer of Aripam Medical Center, one of the largest dermatological clinics in southern Israel. Aripam Clinic is the leading clinic in Israel in Acne phototherapy & esthetic treatment. 2001: He was the a co-author with Dr. Samuel Yorav of the book, titled: “Acne the real story”. Family: Married to Sara and father to Ori and Nadav. 1978: Graduated from the School of Medicine at the Technion, Haifa, Israel. 1979 – 1985: Medical doctor at I.D.F 1985 – 1990: Resident in the department of dermatology in Rambam hospital, Haifa. 1997: A member of the American Academy of Dermatology (AAD). 1991- 2013: Chief executive officer of Aripam Medical Center, one of the largest dermatological clinics in southern Israel. Aripam Clinic is the leading clinic in Israel in Acne phototherapy & esthetic treatment. 2001: He was the a co-author with Dr. Samuel Yorav of the book, titled: “Acne the real story”.

3. Gelatin and safety In 1993 the FDA reiterated the “GRAS” (Generally Reconsidered As Safe) status of gelatin and stated that there was no objection to the use of gelatin from any source and any country provided that the hide from animals showing signs of neurological disease were excluded and also specified raw materials were excluded from the manufacturing process In the year 2000 the European Union approved the use of gelatin In the lecture of Infusion and transfusion therapy by Dr. Madách Krisztina, gelatin is used as an artificial colloid and is used as an I.V. plasma expander with estimated time of 90-120 min and it has the smallest influence on homeostasis among the artificial colloids such as: HES (hydroxyethyl starches) and Dextran (40 Rheomacrodex, 70 Macrodex)* In 1993 the FDA reiterated the “GRAS” (Generally Reconsidered As Safe) status of gelatin and stated that there was no objection to the use of gelatin from any source and any country provided that the hide from animals showing signs of neurological disease were excluded and also specified raw materials were excluded from the manufacturing process In the year 2000 the European Union approved the use of gelatin In the lecture of Infusion and transfusion therapy by Dr. Madách Krisztina, gelatin is used as an artificial colloid and is used as an I.V. plasma expander with estimated time of 90-120 min and it has the smallest influence on homeostasis among the artificial colloids such as: HES (hydroxyethyl starches) and Dextran (40 Rheomacrodex, 70 Macrodex)* *Dr. Madách Krisztina, Semmelweis University Department of Anesthesiology and Intensive Therapy, titled: "Volume resuscitations, pros and cons of crystalloids and colloids, indications and pitfalls of transfusion therapy", 2008, slide 29/33.

4. The hypothesis of therapeutic effect of oral gelatin on hair loss in both men and women 1. Gelatin exhibited one of the highest specific dynamic effects of any food which is caused by increase peripheral blood flow. Increased blood flow had been shown to increase the growth rate of some tissues in both animals and men. 2. Gelatin causes vasodilation of peripheral blood vessels therefore improving the hair follicle blood circulation. 3. Gelatin is composed of 18 amino acids which are delivered via the blood stream to the hair follicle which are the building blocks for hair follicle growth. 4. The hair follicle stays longer time in the anagen stages due to increase availability of the amino acids provided by gelatin consumption. 5. Delaying the progression of the miniaturization of the hair follicle in androgenic alopecia by mechanisms mentions above (1, 2, 3, 4). 6. It is possible that there are changes of signals with the milieu of amino acids in gelatin, through change of proteins produced and released within the hair follicle that promotes and stimulates hair growth in the anagen stage.

5. The specific dynamic action of gelatin* As early as 1926, Rapport et al., discovered that gelatin exhibited one of the highest specific dynamic effects of any food The increase in body temperature due to specific dynamic effect was thought to be cause by an increase in peripheral blood flow This hypothesis is supported by an article in which finger blood volume was found to increase following gelatin ingestion Moreover, increased blood flow had been shown to increase the growth rate of some tissues in both animals and men As early as 1926, Rapport et al., discovered that gelatin exhibited one of the highest specific dynamic effects of any food The increase in body temperature due to specific dynamic effect was thought to be cause by an increase in peripheral blood flow This hypothesis is supported by an article in which finger blood volume was found to increase following gelatin ingestion Moreover, increased blood flow had been shown to increase the growth rate of some tissues in both animals and men * THE SPECIFIC DYNAMIC ACTION OF GELATIN HYDROLYSATES by DAVID RAPPORT, From the Department of Physiology, Western Reserve University Medical School, Cleveland. Received for publication, October 8, 1926. Published the American Society of Biological Chemists, Inc., Vol 71. p. 75-86 in English.

6. Food Derived Collagen Peptides in Human Blood after Ingestion of Gelatin* Identification of several food derived collagen peptides in human blood after oral ingestion of gelatin. Healthy human volunteers ingested gelatin hydrolysates 9.4g - 23g from porcine skin, chicken feet and cartilage and after 12h of fasting. After oral ingestion the peptide form of hydroxyproline (Hyp) significantly increased and reached a maximum level of 20- 60 nmol/ml after 30-60 min and then decreased to half of the maximum level at 5h after ingestion. The ratio of the peptide form of Hyp to the free one was approximately 1:3. Major constituents of food derived collaged peptides in human serum and plasma were identified as Pro-Hyp. In addition, small but significant amount of Ala-Hyp, Ala-Hyp-Glu, Pro-Hyp-Gly, Leu-Hyp, IIe-Hyp and Phe-Hyp were contained. Identification of several food derived collagen peptides in human blood after oral ingestion of gelatin. Healthy human volunteers ingested gelatin hydrolysates 9.4g - 23g from porcine skin, chicken feet and cartilage and after 12h of fasting. After oral ingestion the peptide form of hydroxyproline (Hyp) significantly increased and reached a maximum level of 20- 60 nmol/ml after 30-60 min and then decreased to half of the maximum level at 5h after ingestion. The ratio of the peptide form of Hyp to the free one was approximately 1:3. Major constituents of food derived collaged peptides in human serum and plasma were identified as Pro-Hyp. In addition, small but significant amount of Ala-Hyp, Ala-Hyp-Glu, Pro-Hyp-Gly, Leu-Hyp, IIe-Hyp and Phe-Hyp were contained. *Koji Iwai, et al. article titled: “identification of food derived collagen peptides in human blood after oral ingestion of gelatin Hydrolysates. Department of Food Sciences and Nutritional Health, Kyoto Prefectural University, Japan. Published at the journal of agricultural and food chemistry. 2—5. 53, 6531-6536. DOI 10.1021/jf050206p. Published on American Chemical Society 2005.

8. Effect of gelatin-cysteine diet on growth of human hair* A favorable effect on the growth of hair has been reported in 1982, by Morganti et al. effect of gelatin-cysteine diet supplement on growth of human hair. The study was double blind, lasted 3 month, and involved 40 volunteers aged between 20-40 years. The diet of the volunteers was 2 gram gelatin and 0.8 gram cysteine every day or placebo (starch tablets). The results of this study suggested that the dietary supplementation of gelatin and cysteine combination promoted more intense hair growth and leads to substantial increase in the diameter of the fibers 1-3. A favorable effect on the growth of hair has been reported in 1982, by Morganti et al. effect of gelatin-cysteine diet supplement on growth of human hair. The study was double blind, lasted 3 month, and involved 40 volunteers aged between 20-40 years. The diet of the volunteers was 2 gram gelatin and 0.8 gram cysteine every day or placebo (starch tablets). The results of this study suggested that the dietary supplementation of gelatin and cysteine combination promoted more intense hair growth and leads to substantial increase in the diameter of the fibers 1-3. 1. Morganti P., Randazzo S.D., Bruno C, (1982) "effect of gelatin cysteine on hair after a three months treatment“, J. Soc. Cosmet. Chemists 33, 95. 2. Randazzo S.D., Morganti P., (1982) titled: "The influence of gelatin cysteine supplementation on the amino acids composition of human hair", accepted for presentation on XVI intern. Congress of Dermatology May 23-28 Tokyo. 3. Morganti P., Bruno C. Colelli G (1983) Geltina - cistina. Cheratogenesi e struttura pilifcra Boil, Soc, It. Biol Sper 59:20.

9. Gelatin - cystine therapy in seborrheic alopecia* In 1986, Padova et al. published an article on gelatin- cysteine in seborrheic alopecia in which, 60 Subjects (40 females, and 20 males) affected by Seborrhea alopecia took part. Each volunteer took four capsules a day for 3 month. Every capsule contained 500 mg gelatin and 200 mg l- cysteine (In total 2-gram gelatin and 800 mg cysteine daily). The results were significant reduction in seborrhea in 30% of the subjects and significant reduction in sebum level. In 1986, Padova et al. published an article on gelatin- cysteine in seborrheic alopecia in which, 60 Subjects (40 females, and 20 males) affected by Seborrhea alopecia took part. Each volunteer took four capsules a day for 3 month. Every capsule contained 500 mg gelatin and 200 mg l- cysteine (In total 2-gram gelatin and 800 mg cysteine daily). The results were significant reduction in seborrhea in 30% of the subjects and significant reduction in sebum level. *M.P. DE Padova, A. TOSTI, titled: “Gelatin - Cyctine in Seborrheic Alopecia”, department of dermatology university of Bologna – Italy, February 15, 1985. J Appl. Cosmetol 1968;4;55-60 (April/June 1986).

10. Gelatin effect in androgenetic alopecia:* In yet another article by Morganti et al. he reexamined the influence of gelatin with the addition of cysteine and serenoa repens on hair growth (serenoa repens is commonly known as saw palmetto and sabal serrulatum, it is a small palm tree, normally reaching a height of around 2–4 m). The study was conducted for a long period application of 50 weeks of a new cosmetic lotion, on 48 volunteers (24 women and 24 men) aged between 21 and 38 years, affected by androgenetic alopecia (type 3 and 4 according to Hamilton). 12 subjects also took a dietary supplement (4 pills per day) based on gelatin and cysteine. The solution and the dietary supplement (placebo and active) were assigned in a randomized double blind manner. Hair mass and the mean hair number were controlled according to Price et al. exclusion criteria included use of topical or oral drug or diet supplement within the previous 6 months. The obtained results showed an increase of hair mass from 20 to 30% (p<0.005) together with a contemporary increase of hair number (from 17 to 27%) (p<0.005) compared to the placebo for subject using the lotion only. With the diet supplement a further increase of 50% (p<0.005) in hair growth and significant decrease of blood ROS (Reactive Oxygen Species) were obtained. In yet another article by Morganti et al. he reexamined the influence of gelatin with the addition of cysteine and serenoa repens on hair growth (serenoa repens is commonly known as saw palmetto and sabal serrulatum, it is a small palm tree, normally reaching a height of around 2–4 m). The study was conducted for a long period application of 50 weeks of a new cosmetic lotion, on 48 volunteers (24 women and 24 men) aged between 21 and 38 years, affected by androgenetic alopecia (type 3 and 4 according to Hamilton). 12 subjects also took a dietary supplement (4 pills per day) based on gelatin and cysteine. The solution and the dietary supplement (placebo and active) were assigned in a randomized double blind manner. Hair mass and the mean hair number were controlled according to Price et al. exclusion criteria included use of topical or oral drug or diet supplement within the previous 6 months. The obtained results showed an increase of hair mass from 20 to 30% (p<0.005) together with a contemporary increase of hair number (from 17 to 27%) (p<0.005) compared to the placebo for subject using the lotion only. With the diet supplement a further increase of 50% (p<0.005) in hair growth and significant decrease of blood ROS (Reactive Oxygen Species) were obtained. *Morganti P., G. Fabrizl. B james, C. Bruno, titled: “Effect of gelatin-cystine and serenoa repens extract on free radicals level and hair growth”, Presented at Singapore clinical dermatology 200 – Singapore 18-20 June, 1998

11. Pam Z., Wikonkal N., Pam N., - 15th Annual Meeting of the European Hair Research Society (EHRS), Jerusalem, Israel, July 6-9, 2011. *http://www.ijtrichology.com/article.asp?issn=0974-7753;year=2011;volume=3;issue=3;spage=35;epage=50;aulast =

12. Supportive clinical data for edible compositions for preventing hair loss by a pediatric gastroenterologist and nutritionist* **Inventor Zeev Pam -United states patent application publication: Pub. No.: US 2012/0142598-A1- Jun.7.2012. http://www.freepatentsonline.com/20120142598.pdfhttp://www.freepatentsonline.com/20120142598.pdf

13. Results of gelatin in female pattern hair loss The clinical results in TE are faster than in AGA. In TE the recommended duration of the treatment is 3–6 months while in AGA the clinical treatment is at least 12 months. In females who have both TE and AGA the treatment time depends on clinical results. The clinical results in TE are faster than in AGA. In TE the recommended duration of the treatment is 3–6 months while in AGA the clinical treatment is at least 12 months. In females who have both TE and AGA the treatment time depends on clinical results.

14. Results of gelatin in male pattern hair loss The recommended duration of the treatment in male pattern hair loss is at least 3-6 months of daily dosage of 1.5g-3g of gelatin. According to Dr. Zeev Pam, clinical experience the treatment for male pattern hair loss may even be longer than 6 month with the dosage of 1.5-3 grams gelatin daily or even higher as a gelatin tablet or as gelatin powder. Dr. Zeev Pam, theorized that gelatin supplementation is beneficial in the early stages of androgenic alopecia by dilation of the peripheral blood vessels and supplying the necessary amino acids for the hair follicle and delaying the worsening of the androgenic alopecia stages. Dr. Zeev Pam, suggested that there is a beneficial results from the combination therapy of gelatin with other methods such as: 1. LLLT 2. vitamins and other food supplements and extracts such as: biotin, taurine, zinc, green tea, silica, grape seed, saw palmetto. 3. fatty acids 4. drugs for hair loss treatment such as finasteride, minoxidil and topical revivogen. The recommended duration of the treatment in male pattern hair loss is at least 3-6 months of daily dosage of 1.5g-3g of gelatin. According to Dr. Zeev Pam, clinical experience the treatment for male pattern hair loss may even be longer than 6 month with the dosage of 1.5-3 grams gelatin daily or even higher as a gelatin tablet or as gelatin powder. Dr. Zeev Pam, theorized that gelatin supplementation is beneficial in the early stages of androgenic alopecia by dilation of the peripheral blood vessels and supplying the necessary amino acids for the hair follicle and delaying the worsening of the androgenic alopecia stages. Dr. Zeev Pam, suggested that there is a beneficial results from the combination therapy of gelatin with other methods such as: 1. LLLT 2. vitamins and other food supplements and extracts such as: biotin, taurine, zinc, green tea, silica, grape seed, saw palmetto. 3. fatty acids 4. drugs for hair loss treatment such as finasteride, minoxidil and topical revivogen.

15. Medical indication for the use of gelatin for hair diseases Seborrheic alopecia 1 Improve alopecia of the diffuse type 2 Androgenetic alopecia 3 Telogen effluvium 4 Improves linear growth and diameter of hair 5 Seborrheic alopecia 1 Improve alopecia of the diffuse type 2 Androgenetic alopecia 3 Telogen effluvium 4 Improves linear growth and diameter of hair 5 1. M.P DE Padova, A. TOSTI, title: “Gelatin - Cyctine in Seborrheic Alopecia”, department of dermatology university of Bologna – Italy, February 15, 1985. J Appl. Cosmetol 1968;4;55-60 (April/June 1986). 2. Titled: “Low dosage retinol and L-cystine combination improve alopecia of the diffuse type, following long-term oral administration”. By Hertel H, Gollnick H, Matthies C, Baumann I, Orfanos CE. Universitäts-Hautklinik und Poliklinik, Freien Universität Berlin. Hautarzt. 1989 Aug;40(8):490-5. 3. Morganti P., G. Fabrizl. B james, C. Bruno, titled: “Effect of gelatin-cystine and serenoa repens extract on free radicals level and hair growth”, Presented at Singapore clinical dermatology 2000 – Singapore 18-20 June, 1998 4. Zeev Pam, M.D. presented a lecture titled: "Low dosage gelatin based treatments with single dose, daily, for minimum of 3-6 months in female pattern hair loss." Presented at the first International Annual Convention on the advance in hair research of the Israeli Society of Dermatology and Venereology at the Technion, faculty of medicine, Israel, in June 2010 5. Randazzo S.D., Morganti P., titled: "The influence of gelatin cysteine supplementation on the amino acids composition of human hair", accepted for presentation on XVI intern. Congress of Dermatology May 23-28, 1982, Tokyo.

16. Acknowledgments On behalf of the Pam Family: Sara, Ori and Nadav We would like to thank Prof. Dr. Eli Sprecher and all the members of the Israeli Dermatology Association for honoring the memory of our beloved Zeev Pam 1953-2013. On behalf of the Pam Family: Sara, Ori and Nadav We would like to thank Prof. Dr. Eli Sprecher and all the members of the Israeli Dermatology Association for honoring the memory of our beloved Zeev Pam 1953-2013.