Mesotherapy for Skin Quality

By Dr Loredana Nigro / 08 Aug 2019

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 high-frequency 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.

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

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 HA-based 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 crosspolymerisation 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 healing 22,23 and collagen I synthesis under the application

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

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

Figure 1: Effects of treatment for pigmentation and skin firmness with vitamin C, DMAE, HA, organic silicon. Images courtesy of mesoestetic.

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

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.

References
  1. Konda D, Mesotherapy: What is new? Indian J Dermatol Venereol Leprol. 2013 Jan-Feb;79(1):127-34.
  2. Mesotherapy Worldwide, Physician - Protocol Corner. <http://www.mesotherapyworldwide.com/Mesotherapy_Protocols_Corner.htm>
  3. Sivagnanam G, Mesotherapy the French Connection, Journal of Pharmacology and Pharmacotherapeutics, January-June 2010, Vol 1, Issue 1.
  4. Mesoestetic Mesotherapy Guide, data on file with Dr Loredana Nigro.
  5. Aurora Tedeschi, et al., Mesotherapy with an Intradermal Hyaluronic Acid Formulation for Skin Rejuvenation: An Intrapatient, Placebo-Controlled, Long-Term Trial Using High-Frequency Ultrasound, Aesthetic Plastic Surgery February 2015, Volume 39, Issue 1, pp 129–133.
  6. Kamalpour et al., Injection Adipolysis: Mechanisms, Agents, and Future Directions. The Journal of Clinical and Aesthetic Dermatology [01 Dec 2016, 9(12):44-50]
  7. COUNCIL DIRECTIVE 93/42/EEC, 1993. <https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:31993L0042&from=EN>
  8. Journal of Tissue Engineering, et al., The extracellular matrix: Structure, composition, age-related differences, tools for analysis and applications for tissue engineering’, Journal of Tissue Engineering, 2014 Dec 20;5:2041731414557112.
  9. Human skin pigmentation: melanocytes modulate skin color in response to stress Gertrude-E. Costin,1 and Vincent J. Hearing† talks about pigment
  10. Martine Baspeyras, et al., Clinical and biometrological efficacy of a hyaluronic acid-based mesotherapy product: a randomised controlled study, Arch Dermatol Res. 2013; 305(8): 673–682.
  11. Papakonstantinou, E., Roth, M., & Karakiulakis, G. (2012). Hyaluronic acid: A key molecule in skin aging. Dermato-Endocrinology, 4(3), 253–258. doi:10.4161/derm.21923
  12. Tzellos TG, Klagas I, Vahtsevanos K, Triaridis S, Printza A, Kyrgidis A, et al. Extrinsic ageing in the human skin is associated with alterations in the expression of hyaluronic acid and its metabolizing enzymes. Exp Dermatol 2009; 18:1028-35; PMID:19601984; http:// dx.doi.org/10.1111/j.1600-0625.2009.00889.x
  13. Noble PW. Hyaluronan and its catabolic products in tissue injury and repair. Matrix Biol 2002; 21:25-9; PMID:11827789.
  14. M.A.Croce et al., Hyaluronan affects protein and collagen synthesis by in vitro human skin fibroblasts, Tissue and Cell, Volume 33, Issue 4, August 2001, Pages 326-331.
  15. Gangliang Huang & Hualiang Huang (2018) Application of hyaluronic acid as carriers in drug delivery, Drug Delivery, 25:1, 766-772, DOI: 10.1080/10717544.2018.1450910
  16. JJ, Hampson GN. Orthosilicic acid stimulates collagen type 1 synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro. Bone. 2003 Feb;32(2):127-35
  17. Anderson Oliveira Ferreira et al., Anti-Aging Effects of Monomethylsilanetriol and Maltodextrin-Stabilized Orthosilicic Acid on Nails, Skin and Hair, Cosmetics 2018, 5, 41.
  18. doi: 10.1186/1743-7075-10-2.
  19. Fabiano Svolacchia, et al., Organic Silicium In Aesthetic Medicine: A Review Of Letterature And Meta-Analysis, December 2017/
  20. Margherita Maiol et al., REAC technology and hyaluron synthase 2, an interesting network to slow down stem cell senescence, Scientific Reports volume 6, Article number: 28682 (2016).
  21. Tao Jiang, et al., Structurally Ordered Nanowire Formation from Co-Assembly of DNA Origami and Collagen-Mimetic Peptides, J. Am. Chem. Soc, 2017.
  22. Uhoda, N. Faska, C. Robert, G. Cauwenbergh, and G. E. Piérard, “Split face study on the cutaneous tensile effect of 2-dimethylaminoethanol (deanol) gel,” Skin Research and Technology, vol. 8, no. 3, pp. 164–167, 2002.
  23. B.Sommerfeld, Randomised, placebo-controlled, double-blind, split-face study on the clinical efficacy of Tricutan on skin firmness, Phytomedicine, Volume 14, Issue 11, 5 November 2007, Pages 711-715.
  24. Fabiano Svolacchia, The PDRN (polydeoxyribonucleotide) In Cosmetic Medicine, Biological Introduction, Literature And Meta-Analysis, 2018.
  25. Alfredo Gragnani, et al., Dimethylaminoethanol Affects the Viability of Human Cultured Fibroblasts, Aesthetic Plastic Surgery 31(6):711-8, January 2008.
  26. Su Liu et al., Effects of Dimethylaminoethanol and Compound Amino Acid on D-Galactose Induced Skin Aging Model of Rat, The Scientific World Journal, Volume 2014.
  27. Tadini, K.A et al., In vivo skin effects of a dimethylaminoethanol (DMAE) based formulation, An International Journal of Pharmaceutical Sciences, Volume 64, Number 12, 1 December 2009, pp. 818-822(5).
  28. Johnson KA, et al., Vitamin nutrition in older adults, Clinics in Geriatric Medicine [01 Nov 2002, 18(4):773-799.
  29. Prikhnenko S, Dalens M, Polycomponent mesotherapy formulations for the treatment of skin aging and improvement of skin quality, 7 April 2015 Volume 2015:8 Pages 151—157.
  30. Nermin M. Yussif et al., Evaluation of the Anti-Inflammatory Effect of Locally Delivered Vitamin C in the Treatment of Persistent Gingival Inflammation: Clinical and Histopathological Study, Journal of Nutrition and Metabolism, 2016.

Comments

Log-in to post a comment