An Introduction to Mesotherapy

Mesotherapy for Skin Quality

Dr Loredana Nigro introduces the various mesotherapy options to address skin quality and ageing

Mesotherapy was developed in 1952 by Dr Michel Pistor who described it succinctly as, ‘A little volume, a few times and in the right place’.1 Today, it is a well-established treatment in which liquid or gel compounds are injected intradermally at various depths, at multiple injection sites, to trigger or support aesthetically corrective processes in the skin, through a combination of physical stimulation, pharmacological effect, and appropriate microdosing.1 Although there are many indications – such as cellulite, stretch marks and alopecia – this article will focus on the core ingredients supporting skin rejuvenation. Various injection techniques and devices are used, from manual injection and nappage, to sophisticated devices, which deliver grid dosage of the required substrates, but they are outside the remit of this article.1-3 Mesotherapy is often used synergistically with other protocols, including topical application regimes, intra-dermal treatments such as carboxytherapy (which improves microcirculation and detoxification), or with energy-based treatments such as highfrequency ultrasound.1,4,5

Safe-use guidelines The indications for mesotherapy are broad and usually specific to the combination of injection technique and substrates. Combinations are formulated according to the use, case and experience of the practitioner,1 and one of the main uses of mesotherapy is to improve skin condition and firmness. Inappropriate use of mesotherapy substrates has led to controversy; for example, the injection of phosphatidylcholine for lipolysis has been associated with unpredictable and extreme post-treatment inflammation, and was banned in Brazil in 2002.6 Safe and effective mesotherapy treatments combine professional administration by an aesthetic practitioner with an appropriate selection of injectable components or ingredients.6 In my practice, a useful rule of thumb is that mesotherapy products should bear the CE marking, which certifies that they comply with the relevant EU directive on medical devices.7 The extracellular matrix To understand mesotherapy, it’s useful to consider skin structure, specifically the extracellular matrix (ECM) – the three-dimensional network of macromolecules. These include elastin, collagen and other glycoproteins in the inter-cellular space that support skin structure and therefore appearance. Significant drivers of ageing skin include:8,9 • Loss of collagen and elastin in the matrix – causing volume loss and laxity • Downregulation of the collagen I/III ratio – reducing smoothness of natural repair • Oxidative damage and degradation of the matrix itself • Hyper- or irregular pigmentation

Ingredients Maintaining a competent ECM is crucial to optimising the appearance of the ageing skin. The principal of mesotherapy is to introduce appropriate and effective combinations of compounds into the skin based on their demonstrated pharmacological, metabolic or physical effects on skin ageing.

Hyaluronic acid Ubiquitous in aesthetics, hyaluronic acid, or HA, is a glycosaminoglycan which is a key component of the ECM. It has an important role in skin hydration, healing and structure, as well as the structural functions of other tissues.10 In young adults, approximately 50% of the body’s HA content is found in the skin, but this diminishes rapidly to zero during skin senescence, leading to subcutaneous volume loss and skin ageing.11-13 Studies associate HA with scar-free healing, and increased synthetic ratio of collagen I/III, improving skin quality.14 HA naturally degrades rapidly, and therefore regular intradermal administration supports improved structural rejuvenation.11 In addition to its intrinsic effects, HA is useful as a base delivery substrate for other pharmacologically active mesotherapy ingredients because of its mucoadhesive, biodegradable and non-toxic nature.15 One three-month study looked at the efficacy of a non-cross-linked HA filler delivered by mesotherapy (via serial puncture 2-2.5mm depth) to 55 women with cutaneous ageing signs. One cheek was injected with the HA and the other with saline physiological solution. A trained panel blindly scored skin complexion radiance from standardised and calibrated photographs. They found that non-reticulated HAbased mesotherapy significantly and sustainably improves skin elasticity and complexion radiance.10

Organic silicon Silicon is the third most commonly occurring trace element in humans and is critical in synthesis of collagen and elastin, as well as the cross

Ingredient

Hyaluronic acid

Organic silicon

Highly polymerised DNA

DMAE Formulation

Gel solution with HA. Typically low molecular weight and non-crosslinked.

Typically monomethylsilanetriol and maltodextrinstabilised orthosilicic acid in a HA base (<20Mmol)

Fragmented sodium deoxyribonucleotide, other nucleosides/nucleotides

DMAE in HA base – 0.1-0.5% Lines/wrinkles Firming Dull/dehydrated Acne scaring Pigmentation

Vitamins Multiple vitamins in appropriate concentrations: A,B,C,E,K, coenzymes

Table 1: Mesotherapy ingredient indication matrix for skin rejuvenation and quality. Information amended from table provided by mesoestetic.

polymerisation of collagen – a reasonable proxy for its ‘firming’ effect. In addition, silicon is metabolised by the thymus in humans, which suffers significant age-related atrophy. This is likely the cause for the steep decline of silicon levels in the body as we age.16 While elemental silicon has very low bioavailability, organic silicon compounds such as monomethylsilanetriol and maltodextrin stabilised orthosilicic acid are readily absorbed,17 and in oral administration studies, have led to significant improvements in hair, skin and nail quality.17,18 The local injection of organic silicon has been shown to upregulate hyaluronan synthase 2 and proline hydroxylase, improving fibroblast resilience, local HA synthesis, maintenance of HA levels, and mitigate stem cell senescence.19,20 Synergistic use of injectable organic silicon, along with HA, maximises bioavailability of local components for collagen synthesis, polymerisation (tightening), and improvement of collagen I/III ratios.16,17,19

Highly polymerised DNA A relatively new ingredient in mesotherapy is highly polymerised fragments of DNA (HPDNA).21 HPDNA and, more generally, nucleosides and nucleotides, improve wound healing, mitigate inflammation, and upregulate metabolism in the fibroblasts, which produce collagen.21 HPDNA supports the formation and synthesis of collagen type I proteins in vivo, in preference to collagen III, which leads to a denser ECM typical of younger skin. Controlled trials have demonstrated a marked improvement in in vivo skin would healing22,23 and collagen I synthesis under the application of HPDNA, without adverse outcomes. In my opinion, this suggests potential efficacy in combination with the direct tissue action of mesotherapy and synergistic kinetic or energy-based treatments for rejuvenation, but more studies would be useful.21

Dimethylaminoethanol Dimethylaminoethanol (DMAE) has broad clinical indications, and increased rigidity of the cervicofacial region was noted with oral administration for unrelated conditions in the 1970s.16 Studies have shown significant mitigation of periorbital fine wrinkles, forehead lines and lip fullness with application of topical 3% gel.24,25 Although, potential cytotoxicity concerns have been raised relating to the high 3% concentrations required to topically penetrate the epidermis.16,23 Non-toxic 0.1-0.2% micro-doses of DMAE can be delivered intradermally via mesotherapy, and have been shown to reduce the epidermal and dermal thinning associated with ageing, and to completely mitigate the age-related upregulation of collagen III relative to collagen I.26,27 DMAE has also been shown through in vivo trials to improve dermis thickness and water content of the stratum corneum.26,28

Mesotherapy practitioners will usually choose ingredients that best suit the indication and will formulate combination treatments for individual patients to address their bespoke skin concerns

Vitamins Vitamins are critical for normal rejuvenation, and many older patients have vitamin deficiencies.29 Micro-dosing of various vitamins and coenzymes through mesotherapy can demonstrably improve skin quality, particularly:30 • Vitamin C: a powerful antioxidant that directly ameliorates hyperpigmentation, reduces wrinkles and firms the skin. It has been shown to increase the number of fibroblasts, increasing collagen synthesis and the collagen I/III ratio.31 • Vitamin A: upregulates regeneration of melanocytes and the stratum corneum, has an antioxidant effect, and regulates skin glands and oiliness. • Vitamin E: physiologically supports skin repair. • B-vitamins and coenzymes: support optimal metabolism and physiological development of the skin and ECM.

Treatments and outcomes Mesotherapy practitioners will usually choose ingredients that best suit the indication and will formulate combination treatments for individual patients to address their bespoke skin concerns. An indication grid of common mesotherapy ingredients is explained in Table 1. There are some ingredients that are not listed, however these are the main ones for rejuvenating skin.

Summary Mesotherapy has a broad treatment range. Clinical practitioners can develop their own specific treatment protocols based upon research, experience and recommendations from providers and industry bodies. In my own experience, mesotherapy for skin quality is a demonstrably effective treatment. The periodic intra-dermal introduction of hyaluronic acid, along with pharmacologically active compounds and vitamins, provides a direct approach to rebuild and maintain the ECM – boosting collagen growth and volumisation, normalising pigmentation, and maximising the patient’s critical collagen I/III ratio. Although there is some research, it is limited and more studies would be beneficial in this area.

Dr Loredana Nigro graduated from WITS Medical School in Johannesburg in 2003. She worked in internal medicine in South Africa’s public health sector until 2009, and decided in 2010 to move into aesthetic and antiageing medicine in private practice. She is currently a senior aesthetic clinician at Riverbanks Clinic in Harpenden and works with patients of all ages and skin types. Dr Nigro is also a KOL and clinical consultant for mesoestetic UK.

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