SUMMARY
Evidence is accumulating that cartilage polysaccharides derived from marine fish have a repairing effect on solar elastosis. In a double-blind trial, the efficacy and safety of two commercial preparations, Vivida and Imedeen, were compared in the treatment of sun-damaged skin in women aged 40-60 years. A group of 15 women received 500 mg/day Vivida and another 15 women received 380 mg/day Imedeen orally for 90 days. Subjective assessment revealed statistically significant improvements in skin condition in both treatment groups but Vivida was significantly (P < 0.01) more effective than Imedeen for all parameters. In the Vivida group, mean epidermal thickness increased from 0.14 to 0.26 mm, dermal thickness from 0.90 to 1.51 mm and the elasticity index from 47% to 71%. In the Imedeen group, epidermal thickness increased from 0.13 to 0.18 mm, dermal thickness from 0.80 to 0.97 mm and the elasticity index from 48% to 56%. After 90 days, the differences between the two groups for all three parameters were statistically significant (P < 0.001). The mean erythemal index decreased from 0.24 to 0.20 in the Vivida group, but increased from 0.23 to 0.25 in the Imedeen group. In the Vivida group, five patients developed transient, mild pimples during the first weeks of treatment, but no other adverse effects occurred.

On observe actuellement une accumulation de preuves tendent à montrer que les polysaccharides du cartilage dérivés des poissons marins ont un effet réparateur sur l'élastose solaire. Dans une étude en double aveugle, l'efficacité et la sécurité d'emploi de deux préparations commerciales, Vivida et Imedeen, ont été comparées lors du traitement de la peu endommagée par le soleil de femmes âgées de 40 à 60 ans. Un groupe de 15 femmes a recu 500 mg par jour de Vivida et 15 autres femmes ont recu 380 mg par jour d'Imedeen per os pendant 90 jours. Une évaluation subjective a montré des améliorations statistiquement significatives de l’état de la peau dans les deux groupes, mais Vivida s'est révélé significativement (P < 0.01) plus efficace qu'Imedeen pour tous les paramètres. Dans le groupe trait‚ par Vivida, l'épaisseur épidermique moyenne est passée de 0,14 à 0,26 mm, l'épaisseur dermique de 0,90 à 1,51 mm et l'indice d'élasticité de 47% à 71%. Dans le groupe traité par Imedeen, l'épaisseur épidermique moyenne est passée de 0,13 à 0,18 mm, lépaisseur dermique de 0,80 à 0,97 mm et l'indice d'’èlasticitè de 48% à 56%. Après 90 jours, les diffèrences entre les deux groupes pour les trois paramères étaient statistiquement significatives (P < 0,001). L'indice d'érythème moyen était passé de 0,24 à 0,20 dans le groupe traité par Vivida, mais il avait augmenté dans celui traité par Imedeen, passant de 0,23 à 0,25. Dans le groupe traité par Vivida, cinq patients ont développé des boutons transitoires et bénins pendant les premières semaines du traitement, mais aucun autre effet secondaire n'a été noté.

INTRODUCTION
Premature ageing of the skin due to excessive exposure to sunlight is an increasing problem. Actinically damaged skin or solar elastosis is a clinical entity that is characterized by thinning of the skin, laxity, wrinkles, yellowing, mottling and leathery dryness with variable premalignant and malignant neoplasms.

Photodamaged skin undergoes structural changes. Accumulation of tangled, thickened and abnormal elastic fibres is observed 1,2 , with a simultaneous loss of collagen and an increase in ground substance glucosaminoglycans 3 , and at the end-stage of actinic damage the dermal matrix is almost completely degenerated into an amorphous mass. The dissolution of the collagen and elastin network causes laxity and loss of resilience in sun-exposed areas of the skin. 4

It has been recently shown that extracts from cartilage derived from marine fish have a strikingly good repairing effect on photodamaged skin 5,6. There are, at the present, two commercially available products containing different amounts of active polysaccharides: Vivida tablets contain 500 mg polysaccharides whereas Imedeen tablets contain 380 mg polysaccharides. In the present double-blind clinical trial Vivida and Imedeen were compared when given at the recommended daily doses of 500 and 380 mg, respectively for 90 days.

PATIENTS
The 30 females (age range 40-60 years) with moderate to severe solar elastosis included in the study had exposed themselves to excessive natural sunlight or solarium irradiation for several decades. All patients had skin type II or III, and all were otherwise in good health and had given oral informed consent before they were enrolled in the study.

TREATMENT
At baseline, the study subjects were randomly allocated to one of the two treatment schedules: 15 women (mean age 50 years: mean duration of signs of photodamage 12 years) received 500 mg /day natural polysaccharides (Vivida) taken orally for 90 days: and 15 women (mean age 47 years: mean duration of photodamage 9 years) received 380 mg/day polysaccharides (Imedeen), Intermed Enterprises SA, Switzerland) taken orally for 90 days. The tablets were supplied in identical packages with instructions.

CLINICAL ASSESSMENTS
At baseline and after 90 days all subjects were examined clinically and asked for their subjective impression of the treatment. The following clinical variables were recorded and graded on a three-point scale by the physicians (0, absent; 1, moderate; 2, severe): thinning of the skin; laxity of the skin; wrinkles; mottles; dryness of the skin: brittleness of the hair: and brittleness of the nails. In addition, the thickness of epidermis and dermis was measured 2 cm laterally from the left eye using Dermascan C equipment (Cortex Ltd, Denmark) 7 and the elasticity index of the skin from the left cheek was determined using Dermaflex A equipment (Cortex Ltd, Denmark) 8 . An erythemal index was measured using an erythemal index meter (Diastron Ltd, UK) also using skin from the left cheek. A total of five measurements of each parameter were carried out at each visit and the mean value of the measurements was recorded for each subject.

STATISTICAL ANALYSIS
For statistical analysis, the Student's t-test and the signed test were used.

RESULTS
At baseline, the signs of photodamage were similarly distributed in the patients in the two study groups (Table 1). All patients had severe to moderate thinning of the facial skin, laxity, wrinkles and dryness of the skin. In addition, most of the patients had moderate to severe mottles and brittle nails and approximately half had brittle hair.

At the end of the 90 days' treatment in all patients treated with Vivida, the thickness of the skin was normal as was turgor and the smoothness of the skin (Table 1). Patients in the Vivida treatment group also considered that their nails and hair were normal. In this treatment group there was furthermore a definite improvement in both wrinkles and mottles. In the group treated with Imedeen for 90 days, a definite but less dramatic effect on the clinical parameters was recorded (Table 1). The difference between the two treatment groups was statistically significant (P < 0.01) for all parameters.

Table 2 illustrates the epidermal and dermal thickness, skin elasticity and erythema before and after oral treatment with the polysaccharides. At the baseline, values for the two treatment groups were similar but after treatment with Vivida the patients displayed a larger increase in epidermal and dermal thickness and in skin elasticity than did patients receiving Imedeen; the difference between the two treatment groups was statistically highly significant (P < 0.001). In the Vivida treatment group the mean erythemal index had decreased moderately after treatment, whereas in the Imedeen treatment group a slight mean increase was observed.

In the Imedeen treatment group no adverse effects were reported: however, in the Vivida treatment group five women developed transient mild pimples during the first month of treatment.

DISCUSSION
The results of treatment with Vivida reported in the present study compared well with those previously reported by Lassus et al 5 who administered a daily dose of 500 mg active polysaccharides (Imedeen). A decrease in the daily dose of Imedeen from 500 mg to 380 mg resulted in a marked decrease in the efficacy in the present study, suggesting that the effect of the polysaccharides used was dose-dependent. This observation is supported by the initial results of a study in progress, which has found an increase in pro-collagen, and collagen III in suction blister fluid, and a partial normalization of the histological changes in patients treated with Vivida. No such changes, however, could be observed in patients treated with Imedeen.

Both Vivida and Imedeen caused no or only minimal adverse effects. The mild transient pimples which occurred in one-third of the subjects treated with Vivida were not considered to be of clinical importance.

REFERENCES

1. Sams VM, Smith JG Jr: Alterations in human dermal fibrous connective tissue with age and chronic sun damage. In: Advances in Biology of Skin, vol. 6 (Montagna W. ed), New York: Pergamon Press. 1965: pp 199 - 210.
2. Schwartz W: Morphology and differentiation of connective tissue fibers. In: Connective Tissue (Turnbridge RE. ed). Springfield: Charles C Thomas 1957: pp 144 - 156.
3. Gross J. Schmitt FO: The structure of human skin collagen as studied with the electron microscope. Exp Med 1948: 88: 555 - 567.
4. Parry DAD, Barnes GRS, Craig AS: A comparison of the size distribution of collagen fibrils in connective tissue as a function of age and possible relation between fibril size distribution and mechanical properties. Proc R Soc Lond [Biol] 1978: 203: 305 - 321.
5. Lassus A, Jeskanen L, Happonen HP et al: Imedeen for the treatment of degenerated skin in females, J Int Med Res 1991; 19:147 - 152.
6. Eskelinen A, Santalahti J: Special natural cartilage polysaccharides for the treatment of degenerated skin in females. J Int Med Res 1992:20:99 - 105.
7. Serup J, Holm P, Stender I-M et al: Skin atrophy and teleangiectasia after topical corticosteroids as measured non-invasively with high frequency ultrasound evaporimetry and laser flowmetry: methodological aspects including evaluations of regional differences. Bioeng Skin 1987: 3: 43 - 58.
8. Serup J, Northeved A: Skin elasticity in psoriasis: in vivo measurement of tensile distensibility, hysteresis and resilient distension with a new method: comparison with skin thickness as measured with highfrequency ultrasound. J Dermatol (Tokyo) 1985: 12:318 - 324.
9. Diffey BL. Oliver RJ, Farr PM: A portable instrument for quantifying erythema induced by ultraviolet radiation. Br J Dermatol 1984: 111:663 - 672.

A Eskelinen and J Santalahti
Natural Cartilage Polysaccharides for the Treatment of Sun-damaged Skin in Females: a Double-blind Comparison of Vivida and Imedeen.
The Journal of International Medical Research
1992: 20:227 - 233
Received for publication 23 January 1992
Accepted 25 January 1992

Table 1
Assessment of clinical signs of photodamage to facial skin in women with moderate to severe solar elastosis treated orally with 500 mg/day Vivida (n = 15) or 380 mg/day Imedeen (n = 15) for 90 days

Table 2
Mean epidermal and dermal thickness, skin elasticity and erythemal index in women with moderate to severe photodamage of facial skin treated orally with 500 mg/day Vivida (n = 15) or Imedeen (n = 15) for 90 days