Revista Brasileira De Medicina Vol. 54 - No 3 - March 1997: 144-149
Treatment of Androgenetic Alopecia with a Marine-Based Extract of Proteins and Polysaccharides
Jose Marcos Pereira
Senior lecturer in Dermatology,
Faculty of Medicine of Santa Casa, Sao Paulo
SUMMARY
A group of 200 patients received an oral dose of 600 mg of marine-based extract mixture of proteins and polysaccharides daily for six months as treatment for androgenetic alopecia. 178 patients completed the treatment. A significant decrease of hair loss was observed by 75.3% of the patients and 14.6% of the patients showed partial regrowth of hair. In less severe cases, independently of the duration of hair loss and age of the patients the result of the treatment was significantly superior as compared with patients with long-term severe baldness.
Please note that this is an official English translation of the study ‘Uso de extrato de proteínas e polissacarídeos de origem marinha no tratamento da alopecia androgenética'.
INTRODUCTION
It is historically evident that humans have always taken care of their hair. The hair protects the scalp from trauma and ultraviolet-light, but it has also an important role in a sexual sense serving as a decoration. For this reason hair has been adored and worshipped in different populations, religious groups, mythologies, cultures, social classes and sciences. The loss of hair has an impact upon the sensitive psychological status of a human being. At all times and in all cultures baldness has been treated with various recipes, magical medicine extracts and exotic wonder medicines, but the results of different treatments have always been poor.
There are descriptions of scalp anatomy and formulations for preventing hair loss in over 4000 years old Egyptian papyruses, as mentioned by Ebers and Hearst. One exotic example that can be mentioned is a preventive mixture against hair loss, which included equal amounts of fat from lion, hippopotamus, crocodile, goose and snake. Already Cleopatra advised her lover Julius Caesar, who was severely bald, to indulge house mouse (never a wild one), horse teeth, fat from bear and caribou (bone) marrow. The Egyptian Hakiem-El-Demagh, who has been considered to be the first doctor to be specialized in scalp disorders and illnesses, developed numerous recipes against baldness. Hypocrites’ recommendation for enhancement of regrowth of hair was to massage the scalp with opium blended with rose, cotton and olive oil, or with nettle-extract that was strengthened with dove’s poop.
Van Leeuwenhoek (1632-1723) was the first to carry out scientific research on hair by using a microscope. In 1942, Hamilton took a big step forward in the scientific research of androgenetic baldness by classifying the degree of baldness and by linking hair loss to testosterone and genotype. Since then several attempts have been carried out in order to create anti-androgenic medicines, i.e., drugs that would prevent the effects of testosterone on the hair follicle. The following compounds may be classified as anti-androgenic medicines: cloctol, progesterone, oestrogen, spironolactone, ciprosterone’s acetate, flutamid, cimetidin and cetoconazol. However, none of these is recommendable due to their severe adverse effects. Some drugs, like finasteride, are capable of preventing the function of the enzyme 5-alpha-reductase, but the side effects have limited their usage. Various compounds without any anti-androgenic effect have been used to reduce hair loss and enhance hair regrowth. The following products have no known hormonal effect on the hair follicle: minoxidil, retinic acid, diazoxid, viprostol, ciclosporin etc., as well as the recently discovered protein-polysaccharide mixture obtained from cartilageous fish.
MATERIAL AND METHODS
200 men aged between 17 and 45 were chosen for the trial. Sixty-nine patients (34.5%) were younger than 26 years of age, 57 patients (28.5%) were 26 - 30 years old and 74 patients (37 %) were over 30 years of age. Each patient was treated twice a day with a tablet of 300 mg of a marine-based extract of proteins and polysaccharides for 180 days.
Subjective Impression
The patients were advised to observe changes in the scalp as well as other reactions during the study period.
Duration of Hair Loss
The duration of hair loss was not taken into account, because the start of hair loss is often slow and imperceptible. Few of the patients were able to exactly specify when the hair loss had started, while many of them had noticed the balding when other individuals had started to comment on the thinning of their hair. By that time hair loss and balding had obviously continued for many years unnoticed by the patients.
Clinical Classification
All patients included in the study suffered from androgenetic alopecia. Individuals suffering from patchy non-telogenic baldness were excluded from the study group, because their special features require separate research.
Even though Hamilton, a specialist in anatomy, classified androgenetic alopecia well in theory, it is difficult to use his criteria in practice due to individual variations. The majority of the patients can not be accurately classified with the Hamilton scale, since in the case of some patients the alopecia is localized to the crown, while in other cases to the forehead. In many cases it is situated in the temple area, known as temple baldness. In some patients one specific area remains stable, whereas adjacent areas show a steady progressive mode of balding. The fact that in the early stages of alopecia androgenetica the visible changes are more of a qualitative than a quantitative nature should also be notified.
For practical reasons the study was restricted to an oval area extending from the crown over the temples to the front area. The areas situated in the front and the back of an imagined line from one ear to the other, were evaluated on a five-grade scale based on the severity of the baldness (0= normal hair growth; 1 = mild thinning; 2 = moderate thinning; 3 = severe thinning; 4 = baldness). Each patient was given a classification A(n) and P(m). A referred to the frontal part and P to the back part of the area, whereas ‘n’ and ‘m’ were evaluations according to the severity scale. The classification of a healthy individual would thus be A0P0 and that of a patient with alopecia totalis would be A4P4.
The classification depended on the clinical evaluation because the thinning of hair is in most cases rather a qualitative than a quantitative observation as regards to clinical appearance. When long and thick hair changes into short and thin, it looks thinner, although no real quantitative changes have occurred.
Spontaneous Hair Loss
Each patient was asked to collect spontaneously lost hair daily. Thus, hair found from bath, clothes, towels, bed etc. during a period of five days were counted daily and stored in an envelope.
Density of Hair
A puncture stick for marking the target area was developed. It had a sharp, square head sized 5x5 mm which was gently pressed against the skin in the area where the trichogram was to be carried out. The number of hairs were counted in this square area with the help of a dermatoscope. The number of hairs corresponded to the density of hairs on an area of 25mm2. When multiplied by 4 the density of hairs on one square centimetre (cm2) was obtained.
Trichogram
A trichogram was carried out both at baseline and at the end of the treatment. The analysis was done from an area situated in the intersection of a line between the ears and the interparietal line, i.e., in the sagitalic point. The collection of hairs was performed with the use of a conventional technique.
The Thickness of the Scalp
The thickness of the skin of the scalp was measured in the trichogram area. Local anesthesis was used and a needle was stacked perpendicularly until it reached the periostium. The needle was inserted with the help of a needle holder.
The Rate of Hair Growth
Next to the area where the trichogram was to be performed, a small amount of hairs were cut with a scalpel. After one week the length of regrown hairs was measured and the rate of hair growth (mm/day) could be estimated.
Balding of the Temples
The depth and the width of the bald area were measured from the imagined hair line to the bottom of the bald surface. The measurement was done vertically.
Forehead Baldness
Certain types of androgenetic alopecia occur on the lower forehead. Therefore the distance from the hair line to the middle between the eyebrows was measured.
Calculation of Vellus Hairs
For evaluation of the presence of vellus hairs in areas of normal hair growth, areas of thinning of the hair or bald areas a piece of paper was applied vertically on the scalp. Vellus hairs at the edge of the paper were calculated. The evaluation was carried out in an area where the thinning of the hair was most prominent, independently whether this area was in the front or the back part of the bald area. By plucking, a sample of these hairs were taken for further analysis.
Laboratory Tests
A randomly chosen group of 30 patients was tested for safety reasons. The following tests were done: complete blood count, serum uric acid, ALT, AST and serum urea.
Photography
All patients were photographed at baseline and after the treatment.
RESULTS
Patients and age
200 patients started the six months treatment and 178 (89%) completed the trial. The age of the patients had no influence on any of the test data.
The Subjective Impression of the Patients
No adverse reactions or unexpected events were reported by the patients and the following observations were reported. Altogether 131 (73.5%) observed reduction of hair loss after two months of treatment. 32 (17.9%) of the patients did not observe any reduction of hair loss during the treatment period. 15 patients (8.4%) had never noticed any hair loss during the balding process and were therefore not evaluable for analysis.65 patients (36.5%) had noticed thickening of their hair. 98 patients (55%) did not notice any change in the thickness of the hair. 15 patients (8.4%) claimed that the bald area had increased in size.
Clinical Classification
All participants who completed the treatment were classified from 0-3 both for the front and the back end of the tested area. Patients who in some areas had a value of 4 were not evaluable for this study.
As the evaluation was done on two different areas in each patient (front and back) totally 356 areas were evaluated. The results after the treatment were as follows: in 63 areas the medial value declined from 3.5 (7.9%) to 2. In 115 areas the medial value declined from 2.25 (21.7%) to 1 and in 125 areas the value declined from 1.26 (20.8%) to 0. In 53 areas the initial value was 0 and no changes were observed. In conclusion, out of 240 areas (1 and 2 together) improvement was documented in 51 areas (21.25%). During the six months treatment period deterioration could not be observed in any of the areas.
Density of Hair
The evaluation of the density of hair is difficult, because when calculating the number of individual hairs in a specific area the newly grown, changed hairs, telogenic hairs, will also be calculated along with the normal hairs. It is well known that in the early stages of androgenetic alopecia the changes are more qualitative than quantitative, and only after a long period of time will there be an increase in quantity.
In the beginning of the treatment the average hair density was 210 individual hairs in one cm2. After the treatment the corresponding figure was 218 individual hairs in one cm2. The change was not statistically significant.
Spontaneous Hair Loss
In androgenetic alopecia the spontaneous hair loss is characterized by small, telogenic hairs. The head of this type of hairs has a flame-like shape. The intensity of androgenetic alopecia correlates with a high number of this type of hairs. The daily spontaneous hair loss showed individual variations, but at baseline the average daily hair loss was 75. After six months of treatment the corresponding figure was 40 hairs. The size of the telogenic hairs was slightly bigger after treatment as compared with baseline.
Trichogram
At baseline, the telogenicity varied between 30-70% in the area selected for the trichogram. The severity of telogenisation corresponded to the clinical severity of alopecia. The results were expressed as follows:
•	the telogenicity of 45 (25.3%) patients was 50-70%. In these cases no changes were observed after the treatment period;
•	the telogenicity of 76 (42.7%) patients was 40-50%. In 28 of these the mean telogenicity value decreased 20%;
•	the telogenicity of 57 (32%) patients was 25-40%. In 30 (52.6%) of these cases the mean decrease of the telogenicity value was 30%.
These results showed, that the treatment had a statistically significant improvement of alopecia androgenetica as shown by the laboratory tests.
Thickness of the Skin of the Scalp
The skin thickness of the scalp varied from 4 to 9 mm; in the majority of the patients it varied from 4 to 6 mm. After the treatment no thickening of the skin of the scalp was observed in any of the treated patients.
The Rate of Hair Growth
At baseline the mean rate of hair growth was 0.39 mm per day. After treatment 138 patients (75%) observed an increase in the rate of hair growth, which then reached a mean value of 0.44 mm per day.
Temple Baldness
At baseline 144 (80.9%) patients had more than 3 cm deep bald areas on the temples. The mean depth was 5 cm. These areas did not change during the treatment period.
Forehead Baldness
Altogether 165 (92.5%) patients had a distance of 6 to 7 cm from the hair border line to the eyebrows at baseline. The figures did not change during the treatment.
Estimate of Vellus Hairs
Normally hairs grow in two different ways. In the first case, after hair loss when all hairs are in the growing or anagenic phase hairs grow normally. In the second case, as in androgenetic alopecia, all hairs do not grow normally and a majority of hairs remain in the telogenic phase, which can be seen by the thin and small size of the hairs. The proportion of telogenic hairs in relation to the severity of androgenetic alopecia can be expressed as follows. A low number of hairs on the scalp correlates with a high number of telogenic hairs. The patients classified as 1 and 2 had a moderate number of vellus hairs. Patients classified as 3 had a high number of vellus hairs and the telogenicity was 80-100%. After treatment patients with a classification 3 showed neither quantitative nor qualitative changes. Out of the 240 areas with a classification 1 or 2 153 (63.8%) areas showed a decline of telogenic hairs after treatment. In 57 areas the telogenicity had increased, indicating a detoriation of the androgenetic alopecia.
Laboratory Tests
One of the 30 patients tested for safety showed a minor rise in the ALT and AST values after treatment. No subjective symptoms were reported. Shortly after treatment the laboratory values returned to normal.
Photography
The photographs taken from the patients, clearly showed clinical cure in many cases. Pictures 1-6 present 12 patients with visible regrowth of hair. Each photo shows two patients before and after treatment. The texts under the photos show the clinical classification of the patients.
Further Observations of Interest
•	160 (89.9%) patients observed better growth of their beard.
•	49 (27.5%) observed stronger nails and better growth of nails after treatment.
•	115 (64.6%) patients had red patches on the scalp at baseline, which disappeared during the treatment.
•	21 (11.7%) patients reported better hair growth in other parts of the body, especially on the chest, back and shoulders.
•	4 (4.2%) patients thought they had gained weight.
•	1 (0.5%) patient who had conglobatic acne was completely cured during the treatment.
DISCUSSION
Androgenetic alopecia causes various anatomical changes in the hair and the skin of the scalp. In the present study the advantages of trichology was utilized. Certain tests were of importance while others were rather insignificant. In the following each part of the present study will be discussed and the results will be interpreted.
The subjective impressions of the patients were in general positive, but these must be considered with certain reservations. Many of the patients easily overestimate their symptoms, whereas others are unable to make any observations. The clinical classification was useful, although it is rather subjective and requires great experience from the investigator. With the help of the classification used it was possible to roughly estimate the severity of the disorder. The division into different areas proved to be practically useful. Significant improvement was observed in 21.25% of the original areas, which corresponds to 14.6% of the patients, as two healed areas can appear in one patient. When comparing the values of different areas it was noticed that the results of the treatment were better in cases, in which the balding was in its early stage. When comparing the results between areas classified as 1 or 2 with areas classified as 3, a statistically significant difference was obtained (p<0.05). This leads to the conclusion that the earlier the treatment of androgenetic alopecia is initiated the larger is the likelyhood that positive results will be achieved.The fact that the patients collected spontaneously lost hairs gave important additional information about the decrease in hair loss.
The analysis of the density of the hair is rather quantitative than qualitative and does not indicate healing, the reason why it is better suited in cases with androgenic alopecia of long duration. The trichogram was without doubts objective and showed that healing of hair loss is both clinical and anatomical. This test also clearly showed that the more moderate the baldness is, i.e., the less telogenicity exists, the better treatment results can be achieved. Unless a decrease of hair loss is observed, the decrease of telogenic hairs corresponds to clinical improvement. Although the thinning of the scalp is related to the development of alopecia androgenetica, no such relationship could be observed before or after treatment in the present study. The results of measuring the rate of hair growth showed significance, corresponding with the observation that most patients got improved growth of their beard. However, the correlation between the clinical and laboratory tests with the cure rate could not be shown.
The bald areas on the forehead and the temples remained unchanged during the treatment period, indicating as earlier has been shown that these respond poorly to the treatment. The calculation of the number of vellus hairs was of interest, since a decrease of number of this hair type, meaning a decrease of telogenic hairs meant an increase of the number of anagenic hairs, an indication of that anagenic hairs replaced telogenic hairs. As anagenic hairs have a longer lifespan, a higher amount may result in settlement of the disorder or even partial cure. This result also suggested that the earlier the treatment is initiated the better the new hair will grow.
Taking photographs from the patients prior to and after treatment was of great value showing improvement and should be carried out as a routine procedure when treating different types of hair loss. One patient had a minor increase of the serum ALT and AST values at the end of treatment. The values decreased to normal shortly after the treatment and it is difficult to interpret whether these abnormalities had any relation to the treatment or not. No further adverse reactions were reported or observed.
In conclusion, it is difficult to evaluate the severity of androgenetic alopecia in any studies, since there are so many variables involved. The early changes are more qualitative and quantitative changes can be observed only in cases with long-term hair loss. In addition, there are great individual variations. In the present study, which was based both on clinical and laboratory observations, the results suggest that the use of a marine-based extract mixture of proteins and polysaccharides is beneficial for treatment of androgenetic alopecia in order to reach a stable state of baldness. In early stages of the disorder when balding is mainly qualitative, this treatment results in clinical cure. The age of the patients or the duration of hair loss did not seem to have any effect on the treatment result. None of the patients was completely cured, i.e., got all lost hair back.
Acknowledgements
I want to express my gratitude to Prof. Doctor Manoel Carlos Sampaio de Almeida Ribeiro, Faculty of Medicine of Santa Casa, Sao Paulo, for performing the statistical analyses in the present study.