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5 Vegan Alternatives To Collagen Supplements

Supplements to Promote Collagen Production

What is Collagen and How is it Formed?

Collagen is the underlying structural component of connective tissues such as the skin, cartilage, and bone.1 There are 29 different types of collagen, with collagen type I being the most abundant type in the body.1,2 Types I, II, III, V, VI, VII, XII, XIII, XIV, XVII, and XXIX have been found in the dermis and epidermis.1 The structure of collagen contains a triple helical region and two nonhelical regions.1,2 The triple helix is the defining element in all types of collagen.1

Collagen is made from the amino acids glycine and proline, or glycine and hydroxyproline.2 Collagen synthesis occurs when one of three different types of crosslinking takes place including lysyl oxidase, sugar mediated, or transglutaminase.1 Specialized cells, such as fibroblasts and chondrocytes, will form collagen.1 Fibroblasts form collagen type I and chondrocytes form collagen type II.1 Different vitamins, minerals, and herbs may help enhance collagen synthesis due to their function as cofactors or ability to increase fibroblast activity.1 Co-factors including vitamin C, and copper are required for collagen synthesis as they are essential to the enzymes involved in the process.1 Some of the enzymes required for collagen production include prolyl hydroxylase, lysyl hydroxylase, and lysyl oxidase.1 These vegan alternatives for collagen supplements and herbs may be helpful because they are integral to the synthesis of collagen:

  • Vitamin C
  • Copper
  • Panax ginseng
  • Aloe vera
  • Centella asiatica

Vitamin C

Pre-clinical

Ascorbate is an essential cofactor in the production of collagen.2,3 It is needed during the hydroxylation of proline and lysine residues on procollagen, and increases gene transcription of procollagen.4 While there are several pre-clinical trials, there are limited clinical trials on oral supplementation of vitamin C and collagen production. A study done in 1981 using human skin fibroblasts from a 3-day old boy found L-ascorbate and D-isoascorbate to increase collagen production by 8 times.5 Treatment of the cells resulted in changes in the prolyl and lysyl hydroxylase activities.5

Topical use

A study involving 10 postmenopausal women treated with topical 5% Vitamin C for 6 months showed an increase mRNA levels of collagen types I and III in 6 of the participants.3 An increase in the mRNA levels of the enzymes involved in cross-linking and post-translational processing of collagen were observed as well.3 A pilot study involving 10 individuals treated with a topical containing 10% ascorbic acid, a water soluble acid, and 7% tetrahexyldecyl ascorbate, found an increase of the mRNA for type I collagen after 12 weeks of application.6 This topical was also found to reduce photodamage by decreasing wrinkle severity scores.6

Oral supplementation

There are not many clinical trials specifically looking at oral supplementation of vitamin C for collagen production. A randomized controlled trial with healthy post-menopausal females used a supplement drink containing soy isoflavones, lycopene, vitamin C and vitamin E, along with a capsule of fish oil to evaluate its effects on skin aging.7 After 14 weeks of supplementation, a 10% reduction in wrinkle depth was seen compared to the placebo group.7 Increased levels of collagen were seen in skin biopsies after 14 weeks as well.7 Overall, there is a lack of studies evaluating oral supplementation with vitamin C alone and its effect on collagen synthesis. Further studies are needed to evaluate its efficacy.

Table 1. Vitamin C and Collagen Synthesis

Type of Study

Intervention

Test group

Duration

Outcome

Reference

In-vitro

L-ascorbate and D-isoascorbate

Human skin fibroblasts from a 3-day old boy

 

Increased collagen production by 8 times and prolyl and lysyl hydroxylase activity present

5

Placebo controlled trial

5% Vitamin C topical preparation

10 post-menopausal women

6 months

Increased mRNA levels of collagen types I and III in 6 of the participants

3

Double-blind half face study

10% ascorbic acid, water soluble acid & 7% tetrahexyldecyl ascorbate topical preparation

10 individuals with photodamaged skin

12 weeks

Increased mRNA for type I collagen and decreased wrinkle severity scores

6

 

 

 

 

 

 

Randomized double-blind placebo-controlled randomized study

Supplement drink containing soy isoflavones, lycopene, vitamin C and vitamin E, along with a capsule of fish oil

160 post-menopausal women

14 weeks

10% reduction in wrinkle depth and Increased levels of collagen were seen in skin biopsies

7

Randomized, double-blinded, placebo controlled crossover-design study

5 or 15 g of vitamin C-enriched gelatin

(One hour after the initial supplement, the subjects completed 6 min of jump roping to stimulate collagen synthesis)

88 healthy males

3 days

Increased levels of the amino acids glycine, proline, hydroxyproline, and hydroxylysine were found after one hour of supplementation.

8

 

Copper

Pre-clinical

Copper is essential for collagen fibril assembly.2 The lysyl oxidase enzyme used to form collagen is a copper-dependent enzyme.2 A study using human skin explants exposed to copper ions found increases in elastin and procollagen 1 concentrations compared to the placebo explants after one day of exposure.8 TGF-β levels were also increased after 4 days of exposure in the copper exposed group.8 Another study using skin biopsies of female patients with photoaged skin found a 0.1% copper-zinc malonate cream to increase the accumulation of elastin tissue and elastin biosynthesis.9

Topical use

Copper can be absorbed through the skin and induce proliferation of fibroblasts.10 A study done in 2009 utilizing copper oxide containing pillowcases in women between the ages of 40-60 found a visible reduction in wrinkles and crows’ feet after 2 and 4 weeks of use.10 There were no specific biomarkers used to evaluate the direct effect on collagen production in this study, but an F-ray 3D topography surface measurement camera was used to show reduced wrinkles and skin sagging.10 A similar study was done in 2012 on individuals aged 30-60 and found similar results, specifically with reduction of crows’ feet.11

Another study using a topical gel containing a 0.066% copper chlorophyllin complex was found to improve photodamaged skin in women after 8 weeks of use.12 Assessment was done using photographs and self-assessment questionnaires.12 Currently there are no clinical trials evaluating the efficacy of using oral supplementation of copper alone as in intervention to improve skin quality and collagen formation. However, there are some studies using a combination of antioxidants and minerals, including copper, for this benefit.13

Table 3. Copper and Collagen Synthesis

Type of Study

Intervention

Test group

Duration

Outcome

Reference

In-vitro

Copper ions

Human skin explants

 

Increased elastin and procollagen 1 concentrations after 1 day of exposure

9

In-vitro

0.1% copper-zinc malonate cream

Skin biopsies of 21 female patients with photoaged facial skin

6 weeks

Increased accumulation of elastin tissue and elastin biosynthesis

10

Double-blind, placebo-controlled, parallel, randomized study

Copper oxide containing pillowcase

Women between the ages of 40-60

4 weeks

Reduced wrinkles, crows’ feet, and skin sagging

11

Double-blind, parallel, randomized study

Copper oxide containing pillowcase

Individuals aged 30-60

8 weeks

Reduced wrinkle depth and overall improvement of skin

12

Single-center pilot study

Topical gel containing a 0.066% copper chlorophyllin complex

 

8 weeks

Improved photodamaged skin in women

13

 

Panax ginseng

Pre-clinical

A ginsenoside called compound K, naturally occurs in Panax ginseng, and has been found to decrease the activity of collagen degrading enzymes such as metalloproteinase-1 and cyclooxygenase-2.14 It has also been shown to increase collagen type I expression level as well.14,15 Mouse cells treated with compound K were found to have increased melanin synthesis and skin moisture levels.14

Oral supplementation

A Korean red ginseng extract was used in a randomized controlled study with healthy women participants over 40 years old over a period of 6 months.15 The extract contained 45.3% of powdered Korean red ginseng and 54.6% of powdered Torilus fructus and Corni fructus as a 300mg hard capsule.15 The daily dose was 3g per day, requiring the participants to take 10 capsules per day.15 The researchers found the extract to significantly increase type 1 procollagen expression and fibrillin-1 fiber length in human skin biopsies of the participants.15 Majority of the 86 participants did not experience side effects, however, one of them experienced gastrointestinal upset and dropped out.15 Another proposed mechanism for collagen production by this herb is through its estrogen-like activity, as one study found long term ingestion of ginseng to be associated with swollen and tender breasts.15 Estrogen can effect collagen production since it is known to increase hyaluronic acid synthesis and prevent skin wrinkling.15 Topical application of 17 beta-estradiol has been found to stimulate TGF-beta signaling and increase type I procollagen synthesis.15

Table 4. Panax ginseng and Collagen Synthesis

Type of Study

Intervention

Test group

Duration

Outcome

Reference

In vitro animal study

A stock solution (20mM) of Compound K (from Panax ginseng) in 100% dimethyl sulfoxide (DMSO)

Mouse cells

 

Decreased activity of collagen degrading enzymes such as metalloproteinase-1 and cyclooxygenase-2.

Increased melanin synthesis and skin moisture levels

15

Randomized, double-blind, placebo-controlled study.

Extract containing 45.3% of powdered Korean red ginseng and 54.6% of powdered Torilus fructus and Corni fructus as a 300mg hard capsule taken 10x/day (daily dose 3g)

Women over 40 years old

6 weeks

Increased type 1 procollagen expression and fibrillin-1 fiber length in human skin biopsies of the participants

16

 

Aloe vera

Pre-clinical

The sterol compound in aloe has been found to promote synthesis of type I and type III collagen in human dermal fibroblast cells.16,17 Aloe has also been shown to decrease the collagen degrading MMP-1 gene expression.16 There are studies with conflicting results on Aloe’s function in wound healing, however, a study done on male rats found a topical solution of 5% Plantago major and 5% Aloe vera to increase fibroblast proliferation, collagen bundle synthesis, and re-vascularization in skin wounds after 15 days of use.18

Oral supplementation

A randomized double-blind placebo controlled trial used 40g of an aloe sterol extract in women aged 30-59 and found increased skin barrier function, moisture levels, and elasticity after 12 weeks of use.17 Ultrasound images were used to assess collagen content in the dermis on the forearms of the participants, which were increased after taking the aloe sterol at weeks 4, 8 and 12.17

Table 5. Aloe vera and Collagen Synthesis

Type of Study

Intervention

Test group

Duration

Outcome

Reference

Animal study

A topical solution of 5% Plantago major and 5% Aloe vera

Male rats

15 days

Increased fibroblast proliferation, collagen bundle synthesis, and re-vascularization in skin wounds

19

Randomized double-blind placebo-controlled trial

40g of an aloe sterol extract

64 women aged 30-59

12 weeks

Increased skin barrier function, moisture levels, and elasticity.

Increased collagen content present on ultrasound images.

18

 

Centella asiatica

Pre-clinical

Centella asiatica, otherwise known as Gotu kola, contains the compounds asiaticoside and madecassosode which has been shown to promote fibroblast proliferation and extracellular matrix formation.19 An animal study done on rats found a significantly higher collagen content than the placebo group after 5 and 12 days of treatment with an herbal patch containing Centella asiatica, Echinacea purpurea, and Sambucus nigra.19 Another animal study done on rabbits found an asiticoside rich hydrogel to enhance wound healing over 40% faster than the untreated wounds and 15% faster than commercially available topicals.20 Moderate formation of granulation tissues, fibroblasts, and collagen were seen as well as a thickened epithelial layer.20

Topical application

A randomized controlled comparison study conducted on burn victims in Iran found significantly better wound healing in the group that used a topical centella ointment than the group using 1% silver sulfadiazine after 3 days of use.21 While there was no specific evaluation on collagen production in this study, the centella group was shown to have re-epithelialization and complete healing after 10 days of use.21 

Oral supplementation

A registry study was done using an oral supplement with 225mg Gotu kola leaf extract 3 times a day alongside a hydrating control cream in women with postpartum stretch marks.22 The researchers found an increase in skin thickness after 6 weeks of using the supplement.22 Collagen factors were evaluated using ultrasound imaging and were visibly denser in the oral centella group.22 More clinical studies are needed to evaluate the efficacy of oral supplementation with centella asiaticum on collagen production.

Table 6. Centella asiatica and Collagen Synthesis

Type of Study

Intervention

Test group

Duration

Outcome

Reference

Animal study

Herbal patch containing Centella asiatica, Echinacea purpurea and Sambucus nigra

Rats

12 days

Significantly higher collagen content than the placebo group after 5 and 12 days of treatment

20

Animal study

Asiticoside rich hydrogel

Rabbits with an incisional wound

12 days

Enhanced wound healing over 40% faster than the untreated wounds and 15% faster than commercially available topicals.

Moderate formation of granulation tissues, fibroblasts, and collagen were seen as well as a thickened epithelial layer

21

Randomized controlled comparison study

Topical centella ointment or a 1% silver sulfadiazine topical

75 burn victim patients

2 weeks

Centella group was shown to have re-epithelialization and complete healing after 10 days of use and had better results than the 1% silver sulfadiazine group

22

Registry study

Oral supplement with 225mg gotu kola leaf extract 3 times a day (675mg/d) alongside a hydrating control cream

or

Other stretch mark cream

or

Hydrating control cream only

78 healthy women at least 6 months postpartum with stretch marks

6 weeks

Increased skin thickness, reduced visibility of stretch marks, and visibly denser collagen factors on ultrasound imaging.

23

 

Key Takeaways

  • Topicals containing vitamin C, copper, and Centella asiatica may be useful to promote collagen production. Oral supplementation with Panax ginseng, Aloe vera sterols, and Centella asiatica may be beneficial for collagen production as well.
  • Pillowcases containing copper oxide may be beneficial for patients who don’t want to take something internally, or have a hard time being compliant with topical treatments, since they have been shown to reduce wrinkling after 4-8 weeks of sleeping on them.
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References

References

  1. Sorushanova A, Delgado LM, Wu Z, et al. The Collagen Suprafamily: From Biosynthesis to Advanced Biomaterial Development. Adv Mater. 2019;31(1):e1801651.
  2. Wu M, Crane JS. Biochemistry, Collagen Synthesis. In: StatPearls. Treasure Island (FL)2020.
  3. Nusgens BV, Humbert P, Rougier A, et al. Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis. The Journal of investigative dermatology. 2001;116(6):853-859.
  4. Levine M, Violet PC. Breaking down, starting up: can a vitamin C-enriched gelatin supplement before exercise increase collagen synthesis? The American journal of clinical nutrition. 2017;105(1):5-7.
  5. Murad S, Grove D, Lindberg KA, Reynolds G, Sivarajah A, Pinnell SR. Regulation of collagen synthesis by ascorbic acid. Proc Natl Acad Sci U S A. 1981;78(5):2879-2882.
  6. Fitzpatrick RE, Rostan EF. Double-blind, half-face study comparing topical vitamin C and vehicle for rejuvenation of photodamage. Dermatol Surg. 2002;28(3):231-236.
  7. Jenkins G, Wainwright LJ, Holland R, Barrett KE, Casey J. Wrinkle reduction in post-menopausal women consuming a novel oral supplement: a double-blind placebo-controlled randomized study. Int J Cosmet Sci. 2014;36(1):22-31.
  8. Ogen-Shtern N, Chumin K, Cohen G, Borkow G. Increased pro-collagen 1, elastin, and TGF-beta1 expression by copper ions in an ex-vivo human skin model. J Cosmet Dermatol. 2019.
  9. Mahoney MG, Brennan D, Starcher B, et al. Extracellular matrix in cutaneous ageing: the effects of 0.1% copper-zinc malonate-containing cream on elastin biosynthesis. Experimental dermatology. 2009;18(3):205-211.
  10. Borkow G, Gabbay J, Lyakhovitsky A, Huszar M. Improvement of facial skin characteristics using copper oxide containing pillowcases: a double-blind, placebo-controlled, parallel, randomized study. Int J Cosmet Sci. 2009;31(6):437-443.
  11. Baek JH, Yoo MA, Koh JS, Borkow G. Reduction of facial wrinkles depth by sleeping on copper oxide-containing pillowcases: a double blind, placebo controlled, parallel, randomized clinical study. J Cosmet Dermatol. 2012;11(3):193-200.
  12. Sigler ML, Stephens TJ. Assessment of the safety and efficacy of topical copper chlorophyllin in women with photodamaged facial skin. Journal of drugs in dermatology : JDD. 2015;14(4):401-404.
  13. Genovese L, Corbo A, Sibilla S. An Insight into the Changes in Skin Texture and Properties following Dietary Intervention with a Nutricosmeceutical Containing a Blend of Collagen Bioactive Peptides and Antioxidants. Skin pharmacology and physiology. 2017;30(3):146-158.
  14. Kim E, Kim D, Yoo S, et al. The skin protective effects of compound K, a metabolite of ginsenoside Rb1 from Panax ginseng. J Ginseng Res. 2018;42(2):218-224.
  15. Cho S, Won CH, Lee DH, et al. Red ginseng root extract mixed with Torilus fructus and Corni fructus improves facial wrinkles and increases type I procollagen synthesis in human skin: a randomized, double-blind, placebo-controlled study. Journal of medicinal food. 2009;12(6):1252-1259.
  16. Cho S, Lee S, Lee MJ, et al. Dietary Aloe Vera Supplementation Improves Facial Wrinkles and Elasticity and It Increases the Type I Procollagen Gene Expression in Human Skin in vivo. Ann Dermatol. 2009;21(1):6-11.
  17. Tanaka M, Yamamoto Y, Misawa E, et al. Effects of Aloe Sterol Supplementation on Skin Elasticity, Hydration, and Collagen Score: A 12-Week Double-Blind, Randomized, Controlled Trial. Skin pharmacology and physiology. 2016;29(6):309-317.
  18. Ashkani-Esfahani S, Khoshneviszadeh M, Noorafshan A, et al. The Healing Effect of Plantago Major and Aloe Vera Mixture in Excisional Full Thickness Skin Wounds: Stereological Study. World J Plast Surg. 2019;8(1):51-57.
  19. Chaushu L, Weinreb M, Beitlitum I, Moses O, Nemcovsky CE. Evaluation of a topical herbal patch for soft tissue wound healing: an animal study. J Clin Periodontol. 2015;42(3):288-293.
  20. Sh Ahmed A, Taher M, Mandal UK, et al. Pharmacological properties of Centella asiatica hydrogel in accelerating wound healing in rabbits. BMC Complement Altern Med. 2019;19(1):213.
  21. Saeidinia A, Keihanian F, Lashkari AP, et al. Partial-thickness burn wounds healing by topical treatment: A randomized controlled comparison between silver sulfadiazine and centiderm. Medicine (Baltimore). 2017;96(9):e6168.
  22. Hu S, Belcaro G, Hosoi M, Feragalli B, Luzzi R, Dugall M. Postpartum stretchmarks: repairing activity of an oral Centella asiatica supplementation (Centellicum(R)). Minerva Ginecol. 2018;70(5):629-634.