SUMMARY
VIVIDA when used orally has been previously shown to be effective in treating degenerated skin of women. In the present study, 30 women with moderate to severe sun-damaged facial skin applied VIVIDA cream twice daily for 120 days on one side of the face and placebo to the other. VIVIDA was significantly (P < 0.001) more effective than placebo in improving wrinkles. The effects of VIVIDA cream on mottles and telangiectasis were also significantly (P < 0.01) greater than those of placebo. Scanner measurement showed that epidermal thickness increased from 0.13 mm to 0.29 mm and dermal thickness from 0.91 mm to 1.29 mm on the VIVIDA-treated side; only minimal changes were observed on the placebo-treated side. The elasticity index increased from about 50% to 69% on the VIVIDA-treated side and from 49% to 50% on the placebo-treated side.

KEY WORDS: VIVIDA CREAM, PLACEBO CREAM, SUN-DAMAGED SKIN, BIOLOGICALLY AGED SKIN

INTRODUCTION
Ageing of the skin due to excessive exposure to sunlight or biologically aged skin is an increasing problem. The growing incidence of biologically aged skin is because of the increasing mean age of population in developed countries. Clinical features of solar-damaged or biologically aged skin include thinning of the skin, laxity, wrinkles, yellowing, mottling and leathery dryness with variable premalignant and malignant neoplasms.

When examined histologically photo-damaged skin displays structural changes; accumulation of tangled, thickened and abnormal elastic fibres is typical (1,2) . At the same time, there is a large loss of collagen and an increase in the ground substance glucosaminoglycans (3).. In the final stage of photo-ageing, the dermal matrix becomes almost completely degenerated into an amorphous mass. The dissolution of the collagen and elastin network causes laxity and loss of resilience, especially in sun-exposed areas of the skin (4) .

It has recently become evident that extracts from marine fish, when taken orally, have a strikingly good repairing effect on photo-damaged and aged skin (5,6). In the present double-blind trial, the effects of a 1% cream (VIVIDA cream) were compared with vehicle cream for 120 days.

PATIENTS
A total of 30 females (age range 40 – 60 years) with moderate to severe sun- or biologically damaged facial skin and of skin type II- III volunteered to take part in the study. All women were in good physical health. Oral informed consent was obatained from each patient at the start of the study.

TREATMENT
At baseline, the study subjects were randomized to use either active cream (VIVIDA) on one side and placebo cream on the other side of the face in a double-blind fashion; active and placebo creams were applied twice daily for 90 days. Both creams were packed in jars that looked identical and their consistency was indistinguishable.

CLINICAL ASSESSMENT
At baseline and after 30, 60, 90 and 120 days all patients underwent a physical examination and the skin of the face was clinically evaluated. The following clinical parameters were recorded and graded on a scale of 0 – 3 (0, absent; 1, mild; 2, moderata; 3, severe): thinning of the skin; laxity; wrinkles; mottles; dryness; and telangiectasis. At baseline and after 120 days’ treatment, photographs of treated areas were taken. In addition, the thickness of the epidermis and dermis was measured 2 cm laterally from the eyes using Dermascan C (7) equipment (Cortex Ltd, Denmark) and the elasticity index of skin from the cheeks were determined using Dermaflex A (8) equipment (Cortex Ltd, Denmark). The erythemal index was measured with the use of an erythema index meter (9) (Diastron Ltd., UK) using the skin from the cheeks. A total of five measurements were carried out on both sides of the face at each visit and the mean values of the measurements were calculated and recorded.

STATISTICAL ANALYSIS
Statistical analysis was carried out using the Student’s t-test and the sign test.

All 30 patients (mean age 46 years), who have experienced the clinical signs of skin ageing for a mean of 8 years (range 3 – 21 years), complied with the treatment regimen and attended follow-up examinations as agreed. At baseline the skin’s appearance on both sides of the face was identical (Tables 1 and 2). All patients had a large number of shallow wrinkles (<1 mm depth) on both sides of the face; the majority also had a large number of moderately deep (1mm) wrinkles or deep (>1 mm) wrinkles (Fig. 1). After treatment, no change compared with baseline was observed for the side of the face treated with placebo cream. On the actively treated side, however, all shallow wrinkles were no longer apparent, only three subjects had a few moderately deep wrinkles remaining and in the majority, only a few deep wrinkles were left (Fig 2, Table 1). The difference between the effect of VIVIDA cream and that of placebo cream was highly significant (P < 0.001).

Most patients had moderately or severely thin skin at baseline. The thickness of the skin was improved on the actively treated side in 29/30 of the patients; no improvement was observed on the placebo-treated side after treatment (Table 2). The difference in the two treatment groups was statistically highly significant (P<0.001). The effect of VIVIDA cream on mottles and telangiectasis was significantly (P<0.01) better than that of placebo cream (Table 2). Furthermore, there was a significant (P<0.001) improvement in the dryness of the skin on the actively treated side as compared with the placebo-treated side (Table 2).

The clinical effect of the active cream started very rapidly and dramatically; after 28 days both the trial subjects and the investigator could agree on which side had been treated with VIVIDA. The difference between the two sides increased rapidly for a further 8 weeks, but subsequently even the VIVIDA-treated side changed only minimally.

Scanner measurements showed that epidermal thickness increased from 0.13 mm to 0.29 mm and dermal thickness from 0.91 mm to 1.29 mm on the VIVIDA-treated side, whereas only minimal changes could be observed on the placebo-treated side (P<0.001). There was a significant (P<0.001) difference between the two groups in the changes in the mean elasticity index; it increased form 50% to 69% on the actively treated side and from 49% to 50% on the placebo-treated side (Table 3). The erythemal index was normal on both sides before treatment and did not change significantly on either side during the treatment period.

No adverse reactions were observed or reported. The vehicle was well accpted by the trial subjects.

Table 1
Effect of 1% VIVIDA or placebo cream applied twice daily for up to 120 days on facial wrinkles in 30 women with sun-damaged or age-damaged skin.

Table 2
Clinical effect of 1% VIVIDA or placebo cream applied twice daily for up to 120 days on facial wrinkles in 30 women with sun-damaged or age-damaged skin.

The results of the present study indicated that in addition to changes to the epidermis, the topical application of 1% VIVIDA cream brought distinct changes in the dermis. The results of the present study demonstrated that VIVIDA compared with vehicle cream significantly improved the clinical signs of photo-damaged or biological ageing when applied to the cheeks of women. It was found that thinning of the skin, fine wrinkles and dryness, which are characteristic features of aged skin, were rapidly eradicated when VIVIDA was applied. Furthermore, there was a rapid and dramatic improvement in laxity, deeper wrinkles, mottles and teleangiectiasis. Both clinical and ultrasound evaluations showed that VIVIDA when applied topically had a particularly good effect on epidermal defects and was better than orally administered VIVIDA (5,6). By contrast, orally administered VIVIDA had stronger effects on the dermis compared with the topically applied preparation. These results, therefore, suggest the combined use of oral and topical VIVIDA may bring about even greater repair of damaged skin than moderately use either alone.

The molecular mechanisms by which the natural marine protein in VIVIDA can exert a modulating effect on epithelial differentiations is far from clearly understood. Studies have shown that elastotic changes in mice can be reversed by the topical application of retinoic acid, for example (10). In the case of VIVIDA, however, the mechanism of action has yet to be established.

It is interesting to note that oral and topically applied VIVIDA both bring about improvements to damaged skin. Studies, however, of the absorption of the cream have still to be carried out.

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