Klinisk Studie I
Klinisk Studie av NISIM Shampoo og NISIM Extract
Studiet viser resultater for behandling av Androgenic Alopecia - gentisk hårtap. Nedenfor vises et kort sammendrag av det kliniske studiet. Et mer omfattende sammendrag på engelsk er vist nederst på siden.
Merk også at det finnes et annet studie 'Cellular Changes in Scalp Tissue Biopsies Scalp Biopsi on men with Androgenic Alopecia' som bl.a påviser reduksjon av DHT (DiHydro Testosterone) i hodebunnen ved bruk av NISIM Shampoo og NISIM Extract.
•148 deltagere – alle menn.
• Alder fra 24 til 68 år
•37.5 år gjennomsnittlig alder
• Studiets varighet var på 5 mnd med bruk av NISIM Shampoo og NISIM Extract
• Alle deltagerene var i kategori 3 til 7 på Hamilton Norwood skalaen
• Studie område var på 2,5cm i diameter i områder med lite hår.
• Deltagerne shamponerte hver dag, og brukte Extract hver morgen og hver kveld.
Konklusjon - Klinisk Studie av NISIM Shampoo og NISIM Extract
• De som var i tideligere stadier på Hamilton Norwood viste best resultater.
• Studiet viser at alder på person har ingen betydning for gjenvekst av hår.
• Dosering og riktig bruk er viktig for best resultat.
• Studiet konkluderer med at NISIM shampo og extract er effektive på minst 8 av 10 med Androgenic Alopecia – Genetisk håravfall.
Klinisk Studie - Resultater
85,7 % av deltagerne hadde en 30% økning av hårmengden eller mer.
NISIM Klinisk Studie
Klinisk Studie av ”NISIM New Hair Biofactors”
A.J. Farmilo, Ph.D.
H.L. Minuk,M.D. F.R.C.P. (C)A.B.I.M.
Hår har ingen vital funksjon når det gjelder fysisk velvære hos mennesker. Allikevel bør ikke den psykososiale tilstanden undervurderes. Hodehår kan være feminismens gyllne krone og et potent symbol på maskulinitet og sikkerhet hos menn. Å reversere utviklingen av ’unormalt’ håravfall hos menn og kvinner har i hundreder av år blitt neglisjert fra vitenskaplig og medisinsk hold. Minoxidil (vanligvis kjent som Rogaine) og Diaxozide har vist seg i tidligere studier å kunne reversere skallethet hos menn, skjønt i små prosentvise andeler hos de pasienter som er blitt gjenstand for undersøkelser.
Denne undersøkelsen demonstrerte påliteligheten av NISIM Shampoo og NISIM Extract og produktenes effekt på gjenvekst av nytt hår. Behandlingsopplegget går ut på rensing av hodebunnen med NISIM Shampoo og passende hodemassasje ved bruk av NISIM Extract.
Pasienter og Metoder
Ett- hundre-og-sekstifire menn med gentetisk hårtap fra Toronto-området (Canada) ble undersøkt. Etter samtykke og kartlegging av medisinsk bakgrunn, inkludert den tidsperioden hårtapet hadde utviklet seg, ble pasientene valgt ut. Pasienter som brukte noen form for midler basert på corticosteroid cytotoxic eller andre typer av hårvekstmidler så som minoxidil ble utelatt fra videre undersøkelser. Det ble bestemt at undersøkelsen skulle være uavhengig. Alle deltagere ble omhyggelig forklart og vist hvordan det spesial-lagede middel for rensing av hodebunnen og den sammensatte oppløsning av urter skulle anvendes. Da alt dette var ivaretatt, ble samtlige fotografert med et Minolta ”instant pro” kamera med høy oppløsning. Rommet var godt opplyst for å muliggjøre nøyaktige undersøkelser av hodebunn og individuelle hårstrå. Kameraet ble stilt opp nøyaktig 25 cm fra de hårløse og tynnhårede områdene, og det ble etter behov tatt bilder forfra, bakfra og ovenfra. Deltagerne ble bedt om å vente til bildene var fremkalt og om å undertegne sine respektive bilder.
Gjennomføring og Dosering
NISIM produktene som i sin helhet bestod av urter, ble gratis utdelt til deltagerne. Hver person fikk utdelt 250 ml av NISIM Shampoo og NISIM Extract. Alle deltagerne ble personlig og omhyggelig instruert om hvordan de best skulle bruke produktene.
Vurdering og Gradering
Bildene som ble tatt før behandlingen ble nøye gransket. Før behandlingen begynte, ble en 2.5 cm diameter sirkel tegnet inn på hodebunnen der hårtapet hadde startet og alltid i nærheten av det området hvor hårtapet var betydeligst. Opptelling av hår ble foretatt ved hjelp av et forstørrelsesglass (4x) montert på en sirkulær lampe av lysstoffrør. Uavhengig opptelling ble utført to ganger av to av oss (MS og AJF) og middelverdien av de to opptellingene ble brukt for statistiske formål. Hårstråene innenfor den 2.5 cm- diameter store sirkelen ble tellet opp, inkludert hårstråene på den sirkulære grensen. Etter fem (5) måneder av behandlingsprogrammet, ble den endelige opptelling foretatt. De samme kriteria som ble lagt til grunn for den første fotograferingen ble brukt for å bestemme den nøyaktige beliggenheten av det 2.5 cm-diameter store området på hodebunnen, og den samme prosedyren ble fulgt for å telle hårrøttene innenfor og på grensen for det innsirklede området.
Ved avslutningen av det fem (5) måneder-lange behandlingsprogrammet, ble fotografiene delt inn i følgende grupper:
Gruppe(0): Deltagere hvis bilder ikke viste noen forandring i forhold til bildene som ble tatt ved starten av behandlingen.
Gruppe (1): Deltagerne som hadde moderat gjenvekst sammenlignet med bildene som ble tatt ved starten. Gruppe (2): Deltagere som hadde betydelig gjenvekst i forhold til starten.
Av etthundre-og-sekstifire deltagerne som startet undersøkelsen, ble elleve ekskludert på grunn av gjentatte fravær fra foto-seanser og manglende bruk av produktet. Fire ble ekskludert på grunn av irregulær bruk av både middelet for hodebunnsrensing og av urte-oppløsningen og en person måtte avbryte på grunn av flytting. De resterende 148 deltagere brukte urte-oppløsningen minimum to ganger daglig i fem måneder, slik opplegget for undersøkelsen forutsatte.
Gjenveksten av hår ble registrert hos noen av deltagerne så tidlig som to måneders etter behandlingen startet. Etter tre måneder hadde et betraktelig antall menn moderat gjenvekst; både tynne, lyse, dunete hår og mørkere, halvt utvokste samt fullvokste hårstrå.. Det er viktig å nevne at de tynne, fine hårene, skjønt synlig for det nakne øye, ikke kunne oppdages på bildene. Derfor ble alle våre kvantitative og kvalitative vurderinger basert på halvt utvokste og/eller på fullvokste hårstrå.
Kriteria for å analysere virkningen av Urteoppløsningen
Følgende parametere ble brukt for å klassifisere gjenvekst av hår: Begynnende gjenvekst med mindre enn 30 % økning av halvt utvokste og/eller fullvokste hårstrå ble regnet som ingen forandring. Gruppen som hadde moderat gjenvekst bestod av de personer som under opptellingen etter fem måneders behandling hadde en økning på 30 % -100 % i antall fullvokste hår basert på bildene som ble tatt før og etter behandlingen. Den siste gruppen omfattet de personer som hadde betydelig gjenvekst. Denne gruppen hadde den største økningen av alle menn som var med i undersøkelsen og hadde en gjenvekst på 100 % og større.
Virkningen av NISIM på hårtap og gjenvekst av hår
Skjønt det ble utført uavhengig vurdering av kvalitet og kvantitet viste det seg å være en sterk korrelasjon mellom de to gruppene. Generelt sett hadde 88 % av den kvalitative gruppen forbedring i noen grad. Av den gruppen som ble gjenstand for kvantitativ undersøkelse hadde 85,7 % forbedring av gjenvekst i noen grad (innefor en pålitelighetsgrense av 95 %). Innenfor den kvalitative gruppen var det 6 av 50 menn, tilsvarende 12 % av totalen, som ikke hadde noen gjenvekst. (Gruppe 0) I den kvantitative gruppen var det 14 av 98 menn, tilsvarende 14,3 %, som ikke hadde noen økning av hårveksten. Gjennomsnittlig økning ved opptellingen for denne gruppen var 6,7 %. De fleste personer i denne gruppen fikk derfor noe gjenvekst, men ikke i nevneverdig grad.
Den kvalitative gruppen med moderat gjenvekst (Gruppe 1) bestod av 16 deltagere, eller 32 %. I den kvantitative gruppen var det 44 av 98 menn, eller 44,.9 %, som hadde en økning i området 30 % - 100 %. Økningen var i området 32 % - 98 % med et gjennomsnitt på 61,5 %. I den kvalitative gruppen (Gruppe 2) var det 28 av 50, eller 56 % som hadde betydelig gjenvekst. I den kvantitative gruppen var det 40 av 98, eller 40,8 % som hadde betydelig gjenvekst (Større enn 100 %) Disse menn hadde en økning på 100 % eller mer ved opptellingen. Økningen basert på opptellingen var mellom 102 % og 472 % med et gjennomsnitt på 194 %. Fotografiene av disse menn og kvinner viste betydelige kosmetiske forandringer, noe som stemmer godt over ens med våre kvantitative funn.
Fra fotografiene som ble tatt månedlig gjennom undersøkelsesperioden, ble det observert et mønster i gjenveksten hos de deltagere som hadde betydelig økning i løpet av perioden på 5 måneder. De første hårstrå som lot seg telle, kom til syne øverst eller på kronen av hodet etter 10-12 ukers behandling. Etter videre behandling ble det observert ny hårvekst i ytterkant av det området som var uttynnet eller helt snaut. Gjenvekst foran på hodet og ved tinningene kunne observeres etter 16-20 ukers behandling. Disse områdene viste seg å være de vanskeligst stedene å få håret til å vokse igjen.
Virkning av Behandling vs Alder
Gjennomsnittlig alder av de 176 personene som deltok var 38,7 år. Gjennomsnittlig alder av de respektive gruppene var som følger:
Ingen - forandring: (Gruppe 0): 41,8 år
Moderat-gjenvekst: (Gruppe 1): 36,7 år
Betydelig-gjenvekst: (Gruppe 2): 38,5 år
Den yngste deltager i undersøkelsen var 24 år og den eldste 68 år.
Denne uavhengige undersøkelsen har påvist gjenveksten av hår hos 148 menn som ble behandlet med en urte-ekstrakt anvendt lokalt på hodet der håret var blitt tynt eller blitt helt borte. Behandlingsopplegget omfattet regulær rensing av hodebunnen med natur-ekstrakt og anvendelse av 5-10 ml urte-ekstrakt minimum to ganger daglig. Dataene fra undersøkelsen viser at hårveksten økte betydelig på omtrent 85 % av deltagerne i løpet av fem-måneders-perioden. Metodologien anvendt i undersøkelsen indikerer at resultatene som ble oppnådd ikke bare henger sammen med NISIM urte-ekstrakten som ble brukt i behandlingen, men også med den generelle fremgangsmåten for behandlingen. I tidligere litteratur om minioxidil (Rogaine)ble det påvist at en rimelig forventning til en ”placebo-type” effekt utgjorde 10-15% økning av hårveksten. Ved å sette en grense i disse undersøkelsene for moderat gjenvekst på 30 % økning, vil man kunne se bort fra enhver økning som skyldes en ”placebo-type” effekt.
Det er gjort forsøk på å korrelere virkningen (ingen forandring, moderat forandring, betydelig forandring) med flere faktorer. Ingen av de faktorene som ble undersøkt viste tydelige korrelasjoner, skjønt noen trender ble notert. Antall år håravfallet eller skalletheten hadde utviklet seg, viste seg ikke å ha noen sammenheng med det endelige resultat. Det må imidlertid bemerkes at antall år i denne forbindelse ble oppgitt av deltagerne og kunne ikke bli verifisert nøyaktig. Antall år er gjenstand for vurdering og behøver derfor ikke være særlig pålitelig. For å avhjelpe denne usikkerheten ble resultatene delt inn i grupper. Selv om det ble brukt grupperinger, var det ingen av gruppene som antydet at det var sammenheng med resultatene i betydelig grad.
Hva gjelder gjenvekst av hår, synes denne urte-ekstrakten å være mer effektiv enn minoxidil (Rogaine) og har ingen bieffekter. En studie gjort av Alnais viser at 2 % minoxidil-materiale anvendt lokalt, økte hårveksten med 24 % i løpet av 20 uker. Denne undersøkelsen viste en økning på 89 % over det samme tidsrom. Resultatene er ikke direkte sammenlignbare fordi plasseringen på hodebunnen av de målte områdene var forskjellig Men i en populasjonsstudie viste Alain at 34-46 av 83 deltagere (48 %) ikke hadde noen gjenvekst etter 24 uker, mens vårt resultat viser at bare 14 av 98 (14 %) ikke hadde gjenvekst etter 20 uker.
Her er et før -og etter bilde av en av deltagerne etter 5 måneders bruk av NISIM Shampoo og NISIM Extract
Det ble i studiet 'Cellular Changes in Scalp Tissue Biopsies Scalp Biopsi on men with Androgenic Alopecia' funnet reduserte konsentrasjoner av DiHydro Testosterone i hodebunnen etter bruk av NISIM Shampoo og NISIM Extract.
Link til dette studiet:
Engelsk Sammendrag - Klinisk Studie av NISIM Shampoo og NISIM Extract
Effect of Topical Application of an All Natural Compound Solution on Male Pattern Baldness
A. I. Farmilo, Ph D. M. A. Stratis, R.T. J. S. McGrail, M.D. M.S. F.R.C.S.(C) H. L. Minuk, M.D. F.R.C.P.(C) A.B.LM.
One-hundred-and-forty-eight participants with varying degrees of male pattern baldness (androgenic alopecia) from Stage III to Stage VIII, participated in an open-ended study using an all natural compound solution to determine the effects of hair re-growth.
The participants were photographed and initial hair counts were done in a 2.5cm diameter area of their balding scalp. After five months of treatment the participants were re-photographed and hair counts were done on the same 2.5cm diameter area of the scalp. The results indicate that 85.7% of the men in the study had an increase in their terminal hairs of 30% or greater. When evaluating the percent increase more closely we find that we can break the data down into three separate groups:
- 1. Significant re-growth.
- 2. Moderate re-growth.
- 3. No change.
The group showing a significant re-growth was 40.8% of the study group, and had an increase of 100% or greater (doubling, tripling or more) of terminal hairs counted on their five month post-treatment photo and compared to their initial pre-treatment photo. Of this group the highest increase of hairs was 472%, the lowest increase was 102% with mean at 193.7% increase of hairs.
The group of men showing moderate re-growth, which we classed as 30%I00% increase in terminal hair re-growth, was 44.9% of the study group. The mean increase of that group was 61.5% increase of hair re-growth.
The remainder of the group, classed as no change, was 14.3% of the study group, with the range being minus 13% to +27% increases in hair counts with the mean at 6.7%.
The participants were also classed according to their degree of baldness using Hamilton's classification scheme (See Figure #1) Class IV balding men showed the greatest percent increase at an overall average of 144% more terminal hairs than pre-treatment, with Classes V and VI both slightly less at approximately 120% average increase. Class VII and VIII responded the poorest at 102% and 65% average increases respectively.
Another factor considered was the amount of treatment used during the study. The participants were told to use at least one bottle per month (five bottles in five months) but were allowed to use more if desired. We did not see and significant advantage to using more than one bottle per month. Our conclusion is that the stimulatory effect of the compound is achieved at the use rate of one bottle per month.
The age range of the participants in the ability to re-grow hair was not a factor. The range of the participants in this study was 24-68 years old, with the average age being 38.7 years.
In summary, this study concludes that the Analog Compound has a stimulatory effect on hair growth for at least 8 out of 10 men with androgenic alopecia. The earlier stages of balding appear to respond to a higher degree, but significant improvement was seen in participants at all stages of baldness. There appears to be an optimum rate of use of the product, and age does not seem to be a factor in response. Further studies are being carried out to determine significant factors in the response to the treatment, and to analyze the mechanism of action of the compound.
Hair performs no vital function relative to the medical well being of humans. Yet the psycho-social implications can never be underestimated. Scalp hair can be the crowning glory for the femininity of women and a potent symbol of masculinity and security in men.
Hair consists of a cylinder of impacted, keratinized cells. The hair, together with the 3-layered inner root sheath is formed by the division of cells in the matrix which surrounds the dermal papilla (7, 10). Hair growth varies from individual to individual and from various regions of the body (7).
The correlation of body hair and hormones has long been established as the major cause of balding in men and hirsutism in women (5, 12, 15, 16). The interaction between androgenic hormones like dihydrotestosterone (DHT), receptor sites and the scalp have been a fascinating area of research. At the cellular level, androgens like DHT are transported into the cytoplasm, attached to a cytosol receptor, and are then translocated as a hormone-receptor complex, to the nucleus of the target cells (5, 12, 15). We know the action of testosterone involves the reduction of the hormone itself to DHT by the reducing enzyme 5-alpha reductase (19, 20). Several theories of anti-androgenic action have been put forward to prevent the production of DHT or the binding of DHT to its receptor sites:
1) Inhibit or block the production of the 5-alpha reductase enzyme from acting on testosterone (20) or;
2) prevent the binding of DHT to its target cells by a competitive non androgenic substance (15, 20).
The reversal of male pattern baldness (androgenic alopecia) in men has for century's eluded science and medicine. Minoxidil and Diazoxide have shown in past studies to reverse alopecia in men, although in only small percentages of the patients studied (1, 2, 3, 4, 13, 14).
Other scientific studies done on controlled groups of balding or thinning men was the "Pulsed Electrostatic Field" experiment that reported a good percentage of hair re-growth, but required constant weekly visits to medical offices, thus limiting its universal acceptance (8).
This study demonstrated the safety and efficacy of a natural compound solution to stimulate hair growth. The solution is coupled with a treatment regimen which includes scalp cleansing and proper scalp massaging. This treatment is demonstrated at the Analog Clinic with proper instructions and can then be performed at home.
PATIENTS AND METHODS
One hundred and sixty four males with male pattern baldness from the greater Toronto area were studied at the Analog hair clinic. After informed consent, past medical histories and years of balding, the men were selected. Patients that were using any form of corticosteroids, cytotoxic agents or any other form of hair re-growth agents like minoxidil were excluded from the study. In this study all stages of Hamilton's classification of male pattern baldness were used and none were excluded (6).
Since the methodology involved in this study includes proper scalp cleansing and massaging of the scalp along with the all natural compound solution, it was difficult for us to establish a relevant placebo. The other problem in establishing a relevant placebo was the lack of knowledge of the active ingredients (producing the hair re-growth) in the all natural compound solution, thus it was decided to run an open-ended study.
All men were instructed and shown very carefully how to use the specially formulated scalp cleanser and all natural compound solution. Once this was handled all the men were photographed with a high resolution Minolta "instant pro" camera. The room was brightly illuminated for close examination of the scalp and individual hair(s). The same room and chair were going to be used throughout the duration of the study. The camera was position exactly 25cm from the balding or thinning areas with frontal, top and rear pictures taken as needed. The participants were asked to wait for the picture to develop and sign their respective photos along with the current date.
Administration and Dosage
The all natural compound solution was supplied at no charge to the participants. Each person received 250m1 of the alcohol based all natural compound solution along with 250m1 of a specially formulated deep scalp cleanser. They were all individually and carefully instructed on the proper usage of both the scalp cleanser and all natural compound solution. The stressed importance of proper hygiene and regular application was duly emphasized. All participants were instructed to apply the solution at least three times a day, to the balding or thinning areas of their scalp. They were told to apply 2-3ml of the solution on each application and were further instructed how to massage the scalp firmly.
Classification of male pattern baldness (See Figure #I)
Evaluation and Assessment Grading
The photos taken prior to the treatment were closely evaluated and graded according to Hamilton's classification (Sec Figure #1). Before the treatment was initiated, a 2.5cm circle in diameter was drawn in the balding area, always very near the border of the area demonstrating the most significant hair loss. The circle was located with reference to a precise three point measurement using the bridge of the nose and the intersection of a line drawn using the midway point between the tops of each ear. Initial hair counts were done using 4 X magnifying lens mounted on a circular fluorescent lamp. Independent counts were made by two of us (MS and AJF), times 2, and the average of the two counters were used for statistical purposes. The hairs in the 2.5cm area were counted, including hairs on the circular boundary. The final counts on the participants were done after five (5) months on the treatment program. The same criteria established from the initial photograph was used to determine the exact location of the 2.5cm
area on the scalp and the same procedure was used to count hair roots within and on the boundary of the inscribed circular area.
For the participants in which their photos prior to or after five months of treatment were not countable, a qualitative analysis was done. At the conclusion of the five (5) month treatment program, the photos were graded under the following categories:
A zero (0) grading was given to the photos that revealed no change from their initial pre-treatment photo.
A grading of one (1) was given to the participants with moderate re-growth of hair from their respective original photos.
And a grading of two (2) was assigned to the men with a significant re-growth of hair from their original photos.
This qualitative assessment was made by one person on two different days and, was checked by a second qualified person. The results were found to be consistent between the two graders.
Of the one hundred and sixty-four participants starting the study, eleven were eliminated because of their repeated absence from photo sessions, and failure to use the product. Four were eliminated due to their irregular use of both the scalp cleanser and the all natural compound solution, and one person was discontinued because he relocated to another country. The remainder of the 148 participants applied the all natural compound solution at least twice daily for the five months as required for this study. The participants have committed themselves for at least another three more months of treatment enabling us to do further quantitative analysis after eight months of treatment.
The re-growth of hair was first noticed on some participants as early as two months into the treatment. By the third month, a substantial number of men demonstrated moderate re-growth; both fine vellus hair (peach fuzz) and darker pigmented intermediate and terminal hairs were observed. It is noteworthy to mention that the fine vellus hairs, although visible to the naked cyc, were not detectable by the photos. Thus all of our quantitative and qualitative assessments were made from any intermediate and/or terminal hairs.
Criteria for Analysis of Response to All Natural Compound Solution
Of the 148 participants, 98 had discrete balding areas that allowed us to perform individual hair counts before and after the treatment. The percent increases or decreases were recorded along with other data that was accumulated during the study. The remaining 50 participants were graded qualitatively and graded as discussed previously. The results were analyzed with two major group headings of participants, one with actual hair counts and the second group with no hair counts.
The group that had actual hair counts done had to be closely evaluated and we had to detennine the percentage increase that we considered re-growth. In order to account for the human error in counting the hairs the mean standard deviation between the two counters was determined on all the counts, and was calculated to be +/- 7.38%. Using the 7.38% figure. we calculated 2X the standard deviation of pre-treatment and five month post-treatment counts and determined that participants with less than 29.52% increase in intermediate and/or terminal hairs were counted as no change. This correlated well with no substantial hair re-growth in the corresponding participants photograph. The moderate improvement group we determined were the men that showed an increase of final hair counts of greater than 30% and up to 100% increases of terminal hairs, in their five month photos as compared to their original photos. Their photographic change was more noticeable and also correlated well with their relative percentage increase. The last group we identified was the significant increase group, this group showed the best improvement of all the men in the study and we included those with hair count increases of 100% or greater.
Response of the All Natural Compound Solution on Baldness
Although the qualitative and quantitative assessments were done independently, there was a strong correlation between the two groups (See table #1). Overall, 88% of the qualitative group showed some degree of improvement. Of the group studied quantitatively, 85.7% showed a degree of re-growth (within 95% confidence limits). With the qualitative group, 6 of the 50 men were categorized as having no change (category 0), representing 12% of the total. The quantitative group (98 participants), 14 men or 14.3% did not show any increase in hair counts. The range of hair count increases for this group was (minus) -13% to +27%, with the mean being 6.7%. The photographs of these participants did not show any visible improvement of hair growth.
The moderately improved qualitative group (category I ), consisted of 16 participants or 32%. In the quantitatively studied group, 44 of the 98 men fell into the range of —30% to +100%. This represents 44.9% of the men. The range of increase was 32% to 98%, with the mean at 61.5%. The participants showing significant re-growth in the qualitative group (category 2), was 28 of 50, or 56%. In the quantitatively studied group, the number of men with significant re-growth (greater than 100%) was 40 of 98, or 40.8%. These men had hair count increases of 100% or more. The range of hair count increases was 102% to 472%, with a mean increase of 194%. The photograph of these men showed significant cosmetic changes which correlates very well with our quantitative findings.
Product Safety and Sensitivity Studies
The all natural compound solution had been subjected to the following safety and sensitivity studies:
I) The Mutagenesis Assay also known as the Modified Ames Assay.
II) The Guinea Pig Dermal Photosensitivity and Photoallergenicity study.
III) The Rat Oral LDso Determination test.
The final test results of the all natural compound solution show the solution to be "non mutagenie, non-phototoxiephotoallergenic and no gross pathological changes were found at the end of the Rat Oral LDso study. The LDso was in excess of 5.0 grams, (5.52m1) per kilogram of body weight.
Correlation of Response with Duration of Baldness
There appeared to be no correlation between the efficacy of the product and the duration of baldness. The lowest increase was 89% in the group with over 20 years of balding, followed by a 107% increase in the group balding for 6-10 years. The highest increase of 149% occurred in the group balding for 16-20 years. However, the standard deviation of these values range from 30-70% of the counts, so there is no statistical significance between these values. Assessing the results by the population groupings (no change, moderate change, and significant change), similarly shows no outstanding trends (See Figure #2).
Correlation of Response with Initial Hair Count
The mean initial hair count for the group which showed no increase the mean was 28 (range 10-86), and for the group which showed significant increase the mean was 26 (range 7-58). There is no statistically significant difference between the mean initial hair counts of any of the three groups studied as a function of initial hair counts (See Figure #3), a higher percentage of significant growth occurred in the participants with initial hair counts in the under 30 range (52 +1-14%) than in the participants with initial hair counts over 30 (24 +/-11%). These data imply that although there does not seem to be any relationship between the initial hair counts and the efficacy of the product, there may he a higher chance of significant changes in individuals with lower initial hair counts. This effect could be just a "ceiling" on the total number of hairs which re-grow, thus giving a high percentage increase of those individuals starting from a low number.
Pattern of Hair Re-growth
From those photos taken monthly during the course of the study, a pattern of re-growth was observed in those participants who demonstrated a significant increase in hair counts over the five months. The first countable hairs were seen after 10-12 weeks of treatment and were first detected on the crown or vertex of the head. Following further treatment, hair was then observed re-growing in the margin or fringe of the thinning or balding areas of the scalp. Hair re-growth in the fronto-temporal region of the scalp was noted after 16.20 weeks of treatment, and this region appeared to be the most resistant to re-growth to date. We suspect that 8-12 months further into the treatment, better conclusions can be reached as to the full extent at which the product can diminish whole areas of balding.
Correlation of Response with the Amount of Product Used
Participants were grouped according to the number of bottles of product used during the five month period of the study. Since each bottle contained 250m1 of product, and the recommended rate of use was 5-10m1 twice daily, the expected use rate over the five months was 1500-3000m1 (6-12) bottles, or 250-500m1/month (1-2 bottles/month). However, the participants were allowed by the study to use as much of the product as they wished, and the range of product consumption was 750-6500m1 over the course of the study. or 250- 1300m1/month. Data correlating the response with rate of use are shown in Figures 44 and #5. Figure #4 shows the response based on the monthly use rate, and indicates that the best response occurs with the use of 250-750m1/month. Figure #5 shows the population statistics for these data. Participants have a 46 +1-3% chance of a significant change when using between 250-750m1/month, but only a 25 (1-8% chance of significant change when using more than 750m1/month. From these data, it appears that there is likely a maximum effective dose of the product, probably in the 250-750mlimonth range, and that excessive use of the product does not help the response rate.
Correlation of Response with Stage of Baldness
The results for qualitative and quantitative measured groups were assessed separately for the purposes of this evaluation. From the qualitatively assessed group, the results are shown in Table 2 and Figure 6. The participants with stages IV and V baldness had the best cosmetic (qualitative) result, with an average of 70% showing a significant improvement. The participants with stages III, and VI and VIIMII had a much lower percentage showing a significant increase of only 18%, although those at stage III and VI showed a moderate cosmetic improvement in 30-40% of the cases.
The data from the quantitative results are shown in Table 3 and Figure 7. The data measured from these participants appears to be, on the whole, consistent with the results obtained front the qualitatively measured group, but show much less dramatic changes between the different stages. Stage IV appears to have a much lower response rate in the significant re-growth category (11% compared to 63%), and a much higher response rate in the moderate category (78% compared to 37%). Conversely, the response rate for stages VII and VIII appear to be much higher in the quantitative measurements than in the qualitative assessments. However we could conclude that participants at all stages of baldness have a chance of responding to the treatment, with those at stages HI, IV, V, and VI probably showing the most significant overall improvements.
Correlation of Response with Age
The average age of the 176 participants was 38.7 years. The mean ages for their respective groups were as follows:
The no change group was 41.8 years.
Moderate group was 36.7 years.
Significant group was 38.5 years.
The youngest participant in the study was 22 years old and the oldest participant was 63. There was no correlation between age and response to treatment.
This open-ended study has demonstrated the hair re-growth response of 148 men who have been treated with an all natural compound solution applied topically to balding or thinning regions of the scalp. The treatment program included regular scalp cleansing with a natural extract scalp cleanser and application of at least 5-10m1 of the all natural compound solution at least twice daily. The data showed that hair counts increased significantly for approximately 85% of the participants in the five-month period. Further studies determining the requirement to continue this treatment are planned.
The study methodology implies that the results obtained relate not only to the all natural compound solution used in the treatment, but also the overall treatment regimen. From previous minoxidil papers (2, 21) it was determined by them that a reasonable expectation for a "placebo-type" effect was a 10-15% increase in hair counts. Thus, by setting the cut-off in this study for moderate re-growth at a 30% increase, any increase due to a -placebo-type" effect is discounted.
An attempt was made to correlate the response (either no change, moderate change or significant change) with a number of factors. None of the factors studied gave a strong correlation, although there were some trends noted. The number of years of balding or thinning hair did not appear to have any correlation with the final results. However, it should be noted that the number of years thinning was a number given by the participants and could not be verified accurately. Thus it is a subject of assessment and may not be very reliable. To help balance this uncertainty, the results were grouped. Regardless of the groupings used, there was no grouping which demonstrated a significant correlation with results. This differs from the De Villcz study (2), in which the suggestion is made that the individual most likely to benefit from topical minoxidil treatments was bald less than five years, had a smaller diameter (less than 10cm) of balding arca, and had greater than 100 intermediate hairs in the centre of the balding area. The difference probably results from the method used to determine the area of hair counts in our study. The area counted was always on the edge of the balding area, or in an area with some countable hairs. For the quantitative studies, balding of the type described by De Villez would have been excluded since it was difficult to count accurately more than 150 hairs in the 2.5cm diameter circle. Thus these individuals would have fallen into our qualitative assessed group. Another difference probably arises from the fact that this study will count hairs in the prescribed area regardless of the overall cosmetic effect. An individual who starts with 9 hairs, and increases to 36 hairs would have a 400% increase, and yet the cosmetic effect may not be very significant.
The correlation of response with balding pattern provided an insight that the response might be related to the extent that the cosmetic effect was best at the earlier stages of baldness, and the percentage increase in hair counts was most significant at the middle stages of baldness. This is not unexpected, and it is hoped that this correlation will be proved or disproved during the extension of this study.
The correlation between response and rate of use of the product also demonstrated a maximum effective use rate for the product. This implies that whatever action is resulting in hair re-growth occurs at a certain treatment level, and then cannot be enhanced by additional treatments. This result is subject to the fact that the participants in the study are expected to perform the treatments correctly and consistently. Each participant was shown two to three times how to do the treatments, and each had treatments done in the clinic at their photo intervals each month. This kept a certain control over the application of the product. However, there may be errors in use which would cloud the data in this study.
The mechanism by which the all natural compound solution stimulates hair re-growth is not known. Further studies are currently under way to determine any histological changes on the balding scalp biopsies before and after treatment. The area of particular interest in the ensuing study is to determine if the all natural compound solution has any anti-androgenic properties (15, 20). Medical scientists have been aware that there may be a genetic tendency towards androgenic alopecia (5, 6, 12), but its action is still not entirely clear. Testosterone or BHT, play a role in hair loss, as does blood flow, stress and a number of other factors (6, 7, 20).
Studies have shown the effects of minoxidil and its metabolites at the cellular level, from the point of view of stimulated cell division and cell metabolism and also played a role as a potassium channel opening agent (13). Which of these effects arc responsible for hair growth is not clear. Results from subsequent studies to be reported later may show a role of this all natural compound solution in cell division and metabolic activity.
In terms of hair re-growth, this all natural compound solution appears to be more effective than minoxidil and has no known side effects. A study by Alanis, et al (21) showed that a 2% minoxidil preparation applied topically increased hair counts by about 24% after 20 weeks. This study showed an increase of 89% in the same time period. Because of the differences in locating the measured regions of the scalp, these results are not directly comparable, but in a population study, Alanis' results showed that 34-46 out of 83 participants (48%) had no growth after 24 weeks, whereas our results show only 14 out of 98 (14%) had no growth after 20 weeks. Thus our conclusion is that this product does stimulate re-growth of hair in cases of androgenic alopecia, and that over 85% of men will respond favorably to the
ACKNOWLEDGEMENTS: The authors would like to thank the National Research Council
of Canada (NRC) for their continued advice, assistance and support.