Limonene is a Permeation Enhancer and Boosts Skin Absorption of Vitamins

Posted by Dr. Natasha Ryz on

The delivery of active ingredients into the skin is a challenge.

The outermost layer of the skin is called the stratum corneum.

The stratum corneum is a brick wall that protects you.

Skin Barrier is like a brick wall that protects you from the outside environment

The stratum corneum is very selective about what is allowed to cross the wall and enter your body. 

There are a few who are allowed in - for instance molecules that are small and lipophilic - "i.e. fat-loving" can pass though the wall.

The stratum corneum is supported by other parts of the skin, including a viable epidermis, dermis and subcutaneous connective tissue, and these layers add additional barriers to active ingredients being absorbed into the skin (Gupta et al, 2019).

 Skin Barrier. Stratum Corneum protects you like a brick wall

What is Limonene?

Limonene is a terpene found naturally in citrus peel.

Limonene is the main constituent of essential oils from citrus, including sweet orange, grapefruit, lemon, lime and bergamot. 

Limonene is a Permeation Enhancer and may boost the absorption of active ingredients into your skin

Limonene is widely used in skincare products for its fresh, pleasant citrus aroma. 

Limonene is a well known permeation enhancer (Chen et al, 2016; Mendanha et al, 2017) and can boost absorption of nutrients and active ingredients into your skin barrier (Valgimigli et al, 2012).

What is a Permeation Enhancer?

Permeation enhancers help the skin absorb active ingredients.

More specifically, permeation enhancers are substances that can improve the absorption of drugs or active ingredients through the skin by increasing skin permeability. 

This can be challenging, as the goal is to increase absorption, without causing any damage to the skin barrier. 

Ideally, permeation enhancers should be non-irritating, non-toxic, non-allergenic, compatible with the drugs or active compounds, have good solvent properties, inexpensive, easy removal from the skin and quickly regain its natural barrier (Herman et al, 2015).

Permeation enhancers of the skin include fatty acids, alcohols and glycols, terpenes, surfactants, urea, among others (Gupta et al, 2019).

As permeation enhancers, the most commonly used terpenes include limonene, 1,8-cineole, menthol, nerolidol, and others (Chen et al, 2016).

Due to their high enhancement effect and low skin irritation, terpenes of natural origin are now receiving much attention in pharmaceutical and cosmetic formulations as permeation enhancers (Chen et al, 2016).

What is Your Skin Barrier?

The skin barrier can be described as a "brick-and-mortar" model, where the skin cells called corneocytes are the bricks, and the surrounding fats form the mortar.

Your skin barrier includes the outermost layers of skin, called the stratum corneum.

The stratum corneum is apart of the epidermis, which is the outer layer of your skin.

The epidermis is mainly made of skin cells called keratinocytes. 

Layers of the skin barrier

As keratinocytes get older, they migrate up the cell layers are turn into corneocytes, and populate the stratum corneum.

So the stratum corneum is filled with corneocytes (dead skin cells), and is the outer layer of the epidermis.

Skin Barrier. Your Stratum Corneum is a brick wall that protects you

When your skin barrier is healthy, it feels and appears smooth, soft, and plump.

In contrast, a damaged skin barrier looks dry, rough, dull, and dehydrated, and may become irritated and inflamed.

Learn More: What is Your Skin Barrier?

How does Limonene Increase Absorption?

Essential oils and their terpenes have been widely investigated as safe and suitable skin penetration enhancers for both hydrophilic and hydrophobic drugs but mechanism of their action is not fully understood (Herman et al, 2015).

There are only few possible pathways for epidermal penetration of active compounds, which include:

  1. Penetration through the intercellular spaces of the stratum corneum.
  2. Appendage penetration through hair follicle, sebaceous and/or sweat glands.
  3. Transcellular (intracellular) permeation across the corneocytes of the stratum corneum.


Drug permeation routes across the skin. Herman et al, 2016

(Herman et al, 2016)

Can Limonene increase absorption of Active Compounds?

Essential oils have been shown to be successful in delivering a range of different drugs across the skin including: 5-FU, ibuprofen, p-aminobenzoic acid, labetolol hydrochloride, flurbiprofen, piroxicam, trazodone hydrochloride, estradiol, ketoconazole, chlorhexidine digluconate, nitrendipine, diclofenac sodium, indomethacin, benzoic acid and carvedilol (revewed by (Herman et al, 2015).

However, more research is required to understand the exact mechanism of absorption.

Limonene has been shown to increase the skin absorption of various topical compounds and drugs (reviewed by Chen et al, 2016 and Herman et al, 2016).

Can Limonene increase absorption of Vitamins?

Topical bioavailability of lipid- and water-soluble vitamins is a critical issue for skincare formulations.

Using 17-day-old SkinEthic(®) reconstructed human epidermis, Valgimigli et al, 2012 studied the role of lemon essential oil in enhancing the penetration of α-tocopherol (vitamin E) and retinyl acetate (vitamin A), pyridoxine (vitamin B6) and ascorbic acid (vitamin C), released from oil in water (O/W) or water in oil (W/O) emulsions.

Lemon essential oil contains 60-78% limonene, as well as 2.2% α-pinene and 0.5% p-cymene.

Individual terpenes, D-limonene, α-pinene and p-cymene had skin permeability coefficients Ps (10(-3) cm h(-1)) of 0.56 ± 0.03 (or 0.73 ± 0.02), 0.72 ± 0.05 (or 0.98 ± 0.05) and 0.84 ± 0.04 (or 1.14 ± 0.04), respectively, when incorporated in a W/O (or O/W) emulsion (Valgimigli et al, 2012).

Vitamins B6, C and A had Ps values of (3.0 ± 0.4) × 10(-3), (7.9 ± 0.6) × 10(-3) and (0.37 ± 0.02) × 10(-5) cm h(-1), respectively, and their flux through the skin was enhanced by a factor of 4.1, 3.4 and 5.8, respectively, in the presence of lemon essential oil. The penetration of vitamin E was nine-fold enhanced.

Lemon essential oil produced only reversible modification of of the skin barrier, as determined through transepidermal water loss (TEWL), and it is a safe and effective penetration enhancer for topical administration of lipid- and water-soluble vitamins.

However, more research is required to determine is limonene as a single compound can increase absorption of vitamins into the skin.

Is Limonene Safe?

After applying to the skin, essential oils and their components are rapidly metabolized, not accumulated in the organism and fast excreted, which strongly suggests that they can be successfully use as safe penetration enhancers (Herman et al, 2016). 

Limonene is considered to have low toxicity (reviewed by Sun, 2007) and is recognized as a safe ingredient for skincare under the current regulatory guidelines for cosmetics (reviewed by Kim et al, 2013). 

Read More: Is Limonene Safe for Your Skin? Yes! 


The delivery of active ingredients into the skin is a challenge.

Limonene is a well known permeation enhancer and may boost absorption of nutrients and active ingredients, including vitamins into your skin barrier.

However, more research is required.


Almirall, M.; Montaña, J.; Escribano, E.; Obach, R.; Berrozpe, J.D. Effect of d-limonene, alpha-pinene and cineole on in vitro transdermal human skin penetration of chlorpromazine and haloperidol. Drug Res. 1996, 46, 676–680.

Api AM, Ritacco G, Hawkins DR. The fate of dermally applied [14C]d-limonene in rats and humans. Int J Toxicol. 2013 Mar-Apr;32(2):130-5.

Aqil M, Ahad A, Sultana Y, Ali A. Status of terpenes as skin penetration enhancers. Drug Discov Today. 2007 Dec;12(23-24):1061-7.

Ahad A, Aqil M, Kohli K, Chaudhary H, Sultana Y, Mujeeb M, Talegaonkar S. Chemical penetration enhancers: a patent review. Expert Opin Ther Pat. 2009 Jul;19(7):969-88. 

Charoensumran P, Ajiro H. Cationic Moieties in Polystyrene Gels Swollen with d-Limonene Improved Transdermal Delivery System. Polymers (Basel). 2018 Oct 27;10(11):1200. 

Chen J, Jiang QD, Chai YP, Zhang H, Peng P, Yang XX. Natural Terpenes as Penetration Enhancers for Transdermal Drug Delivery. Molecules. 2016 Dec 11;21(12):1709.

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Gupta R, Dwadasi BS, Rai B, Mitragotri S. Effect of Chemical Permeation Enhancers on Skin Permeability: In silico screening using Molecular Dynamics simulations. Sci Rep. 2019 Feb 6;9(1):1456.

Herman A, Herman AP. Essential oils and their constituents as skin penetration enhancer for transdermal drug delivery: a review. J Pharm Pharmacol. 2015 Apr;67(4):473-85.

Sapra B, Jain S, Tiwary AK. Percutaneous permeation enhancement by terpenes: mechanistic view. AAPS J. 2008;10(1):120-32.

Sun, J. D-Limonene: Safety and clinical applications. Altern. Med. Rev. 2007, 12, 259–264.

Takayama K, Nagai T. Limonene and related compounds as potential skin penetration promoters. Drug Dev Ind Pharm 1994; 20: 677–684.

Valgimigli L, Gabbanini S, Berlini E, Lucchi E, Beltramini C, Bertarelli YL. Lemon (Citrus limon, Burm.f.) essential oil enhances the trans-epidermal release of lipid-(A, E) and water-(B6, C) soluble vitamins from topical emulsions in reconstructed human epidermis. Int J Cosmet Sci. 2012 Aug;34(4):347-56.

Yang, Z.; Teng, Y.; Wang, H.; Hou, H. Enhancement of skin permeation of bufalin by limonene via reservoir type transdermal patch: Formulation design and biopharmaceutical evaluation. Int. J. Pharm. 2013, 447, 231–240.

Zhang CF, Yang ZL, Luo JB. [Effects of D-limonene and L-limonene on transdermal absorption of ligustrazine hydrochloride]. Yao Xue Xue Bao. 2006 Aug;41(8):772-7. Chinese.

Essential Oil Safety Essential Oils Limonene Skin Barrier Skin Science Terpenes

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