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A (ridiculously) deep guide to getting great skin with Vitamin C

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This writeup was lead-authored by our senior technical adviser, Sunbin Song, PhD. Sunbin graduated from MIT with a degree in Biology before receiving a doctorate in neuroscience from Georgetown and becoming a research scientist at National Institute of Health. 

Hi there! Welcome to Maelove’s “More than Skin Deep” series. In this writeup, we go deep into how Vitamin C helps your skin and what you should look for when choosing a Vitamin C skincare product. 

Is Vitamin C in skincare just a hype? Or is it a real deal? You'll find out here.

What’s covered:

  • What makes Vitamin C such a good skincare ingredient?
  • What should I look for in a Vitamin C based skincare product?
  • If I already consume Vitamin C in my diet, why do I need to apply it on my skin?
  • Should I look specifically for ascorbic acid? How about the other types of Vitamin C?
  • Do I need to specifically look for L-ascorbic acid? Or is ascorbic acid acceptable?
  • How often and when should I apply?
  • Should I use Vitamin C if I have acne or rosacea?
  • Are there any drawbacks when it comes to using Vitamin C products?
  • Final thoughts and Appendices.

A quick note: This writeup is meant to provide you with helpful information that can be verified with publicly available information. So, there are no mentions of proprietary research or specific product recommendations.

 

What makes Vitamin C such a good skincare ingredient?

There is a simple reason your dermatologist keeps recommending Vitamin C: topically applied Vitamin C is one of the best proven ways to keep your skin healthy.

What makes Vitamin C such a good skincare ingredient

Vitamin C improves your skin in 3 key ways:

  • Vitamin C resists premature aging caused by the sun’s Ultraviolet (UV) rays
  • Vitamin C keeps your skin looking and feeling bouncier by boosting collagen production
  • Vitamin C helps brighten your skin and evens out the tone by preventing sun spots, melasma and acne marks (hyperpigmentation caused by UV or inflammation)

Sounds great, right? Let's delve deeper into how Vitamin C works for your skin.

 

Benefit 1 - Vitamin C is an effective antioxidant that protects your skin from premature aging by sun damage

As you may know, UV rays from the sun are the main cause of premature aging of skin.

When your skin is exposed to UV rays, free radicals are spawn. These free radicals can then cascade through your skin like ricocheting bullets tearing up collagen and wreaking havoc on your skin cells. 

UV spawns free radicals

Free radicals cause premature aging

The damages caused by free radicals speed up the aging process in human skin, which we see visibly as sunspots, wrinkles and ruptured blood vessels (called actinic purpura - which is bleeding from fragile capillary blood vessels just beneath the skin surface).

Of course, there is nothing wrong with getting older! But why rush it?

As you know, wearing a good broad spectrum SPF is still the most important thing you can do for anti-aging. However, even good sunscreens only block about half of the free radicals spawned from UV exposure (Telang et al 2013).

Free radicals are vicious on your skin and skin cells, so you want as much protection against free radicals as possible. That’s where antioxidants come into play.

Cells use Vitamin C to neutralize free radical

Antioxidants can clean up roving free radicals in your body like water puts out fire. So, ramping up topical antioxidants like Vitamin C is a great way to keep your skin looking youthful and healthy.

The good news is that sunscreen and antioxidants protect your skin in different ways (you aren't just doubling up on the same thing), so using them together is complementary and boosts each other’s effectiveness.

You can read more in depth about free radicals and skin health in Appendix A at the end of this writeup.

Wait! How about blue light?

Blue light is within the spectrum of visible light, and you can get blue light from a light bulb or a phone screen. While you only get UV light outside (from the sun), you can be exposed to blue light both indoors and outdoors, during the day and at night.

If you stare at a screen all day, you may be tanning your face a little with the blue light emitted by the screen (especially if your skin is very fair).

And it’s possible that blue light can increase free radicals in your skin. Although, in our view, it’s very unlikely that the blue light from screens can inflict significant damage to your skin.

There hasn’t been much research on whether antioxidants work specifically against the effects from blue light exposure. However, we believe that Vitamin C should work just fine because antioxidants work against free radicals in general.

To summarize, Vitamin C is good for your skin even if you stay indoors all day. 

Wait, one more question! How about cigarette smoke or pollution?

Yes, these things can also cause free radical creation. And yes, Vitamin C helps there as well.

 

Benefit 2 - Vitamin C is a collagen booster, and it will help keep your skin firmer and bouncier

Collagen is what keeps your skin from wrinkling and sagging. Therefore, you want to preserve the collagen you have and continue regenerating it regularly.

Your skin looks smoother and firmer with healthy collagen

 

collapsed collagen and skin

Collagen is an elongated fibrous protein. When seen under a microscope, collagen looks like braided steel cables and provides structure and support to your skin like scaffolding under a tent.

We steadily lose collagen in our skin over time - roughly 1% per year - which leads to wrinkles and sagging as we get older. In women, collagen loss can be dramatically sped up during menopause.

Without the supportive collagen fibers, your skin loses strength and flexibility. Skin then begins to sag and wrinkle.

As we mentioned in the previous section, Vitamin C, in its role as an antioxidant, can protect and preserve collagen from destruction caused by UV exposure and free radicals. In addition, Vitamin C can also help rebuild and regenerate collagen as well, thereby partially reversing the negative effects of collagen loss.

Vitamin C boosts collagen formation both by fueling production of the building blocks of collagen (procollagen peptides) and by helping enzymes weave these peptides into collagen fibers.

VC boosts collagen

So, you can think of Vitamin C as a collagen booster. If you want to keep away wrinkles and sagging as long as possible, Vitamin C can help.

  • Vitamin C upregulates mRNA production of collagen polypeptides for type I and III by increasing transcription of the genes and stabilizing the transcripts (Nusgens et al. 2001).
  • Vitamin C is used as a cofactor for enzymes necessary to cleave and fold the collagen polypeptides into a triple helical shape that then forms the collagen fibers (Nusgens et al. 2001).
  • Vitamin C also inhibits the breakdown of collagen by inhibiting the synthesis of collagenase 1 (Nusgens et al. 2001, Pullar et al. 2017).
  • These benefits have been demonstrated in placebo-controlled studies of intrinsically aged skin in postmenopausal women (Nusgens et al. 2001) as well as photo-damaged skin (Traikovitch 1999) with improvements also noted in skin appearance for fine wrinkling, tactile roughness, coarse rhytids, skin laxity/tone, and sallowness/yellowing.
  • Note that the necessary role of Vitamin C in collagen formation also leads to its beneficial role in wound healing and skin repair, and its role in the development of scurvy when Vitamin C is severely lacking (Pullar et al. 2017).

 

Benefit 3 - Vitamin C brightens and evens out your skin tone by reducing hyperpigmentation (such as dark spots and acne marks)

Hyperpigmentation is a condition when patches of skin get darker than their surroundings, and it occurs when there is an overproduction of melanin - which are dark pigments responsible for skin color.

hyperpigmentation caused by UV

Common causes of hyperpigmentation are sun exposure and inflammation (such as acne). Excessive UV radiation and inflammation can stimulate melanocytes to push melanin production into overdrive. Melanin is encapsulated in organelles called melanosomes which are transported to the skin surface to induce pigmentation (DeDormeal et al. 2019).

Melanin typically serves to protect against UV radiation so in principle, is good for you. However, the aesthetic side effects of hyperpigmentation, sunspots, and melasma are often unwanted in terms of appearance.

Vitamin C tempers overproduction of melanin, and helps keep the unwanted aesthetic side effects of hyperpigmentation at bay. Vitamin C inhibits the enzymatic activities that make melanin in your skin, so you get a brightening effect.

VC can moderate hyperpigmentation

Published research suggests a minimum 10% Vitamin C concentration in order to get the full benefit of fighting hyperpigmentation.

Then Vitamin C goes a step further. Vitamin C is also an effective anti-inflammatory that can promote skin healing thus further helping to prevent unwanted blemishes and scars from forming in the first place.

  • Vitamin C inhibits an enzyme involved in melanin synthesis (tyrosinase) which leads to reduction of melanin and melanin intermediates such as dopaquinone (DeDormeal et al. 2019, Pullar et al. 2019).
  • Topical Vitamin C reduced UV induced skin pigmentation. In a meta-analysis (study of studies) of 31 Randomized placebo-controlled studies, Vitamin C successfully showed a concentration reliant ability to reduce pigmentation increases from UV light exposure (DeDormeal et al. 2019).
  • The beneficial effect was low at 2% Vitamin C concentration, moderate between 3-7%, and had the highest effect at 10% (DeDormael et al. 2019). (Note to reader: This suggests that to get the benefits of reduced hyperpigmentation, a concentration of Vitamin C in any topical product you consider should be at least 10%).
  • Specifically, at 10% concentration, 85% of subjects showed a strong reduction in pigmentation, 13% a moderate reduction, and 2% a mild reduction. At 2% concentration, 0% showed a strong reduction, 15% a moderate reduction, and 85% showed a weak reduction.
  • Vitamin C can also inhibit proinflammatory cytokines and hence as an anti-inflammatory agent can be used to treat acne or rosacea, as well as promote wound healing and prevent post-inflammatory hyperpigmentation (Pullar et al. 2017).

 

OK, I’m convinced. What should I look for in a Vitamin C product?

Look for these 3 things at minimum: (1) 10% or higher ascorbic acid (2) Addition of Vitamin E and other antioxidants (3) Acidic formulation of pH 3.5 or below

Look for: 10% or higher ascorbic acid

As we mentioned in the section above on hyperpigmentation, in order to enjoy Vitamin C’s skin brightening benefits, make sure the product has a minimum 10% ascorbic acid.

VC and AA

Look for: addition of Vitamin E and other antioxidants

The presence of other antioxidants can help stabilize ascorbic acid and also boost the skin benefits. Think of these additional antioxidants as the supporting cast to the star, ascorbic acid.

Vit C is like batman

Two of the most well known and proven boosters of ascorbic acid are Vitamin E and ferulic acid.

Therefore, we recommend that you look for products that feature Vitamin C (ascorbic acid), Vitamin E and ferulic acid at a minimum.

  • Vitamin C is hydrophilic while Vitamin E is lipophilic, and the two together protect hydrophilic and lipophilic components of the cell. In fact, without this synergy between Vitamin C and E, each in isolation is minimally effective.
  • Vitamin E potentiates antioxidant efficacy of Vitamin C four-fold (Lin et al. 2003).Ferulic acid (a potent antioxidant of plant origin) when combined with Vitamins C and E increases the antioxidant efficacy of Vitamin C eight-fold (Lin et al. 2005).
  • Vitamin C is particularly effective as an antioxidant when used in conjunction with Vitamin E, as Vitamin C regenerates oxidized Vitamin E.

 

Look for: acidic pH

Acidic pH is needed

You’ve probably already heard a lot about Vitamin C serums being acidic. The reason is because ascorbic acid needs to be in a low pH (acidic) formulation for it to be able to penetrate the skin surface barrier.

To summarize simply, electrically neutral molecules are potentially able to get through the water-proof skin surface barrier. And at a low pH, ascorbic acid is in an electrically neutral form. This is why effective Vitamin C serums are all acidic.

We suggest a product with a pH of 3.5 or lower, which is around the same acidity as wine. 

The need for acidity is why we recommend Vitamin C serums in a water based formula, rather than a cream. It’s much easier to achieve the needed level of pH in a water based formula.

You can read more about how ascorbic acid can be formulated to penetrate the skin surface barrier in Appendix B at the end of this writeup.

 

If I already consume Vitamin C in my diet, do I need to also apply it on my skin?

You should apply Vitamin C directly on your skin because ingesting Vitamin C isn’t enough to maintain optimum skin health.

The basic reason is simple. When you ingest Vitamin C, it’s taking a long, roundabout way to reach your skin - going from gut to bloodstream to skin tissue. And there is a limit on how much Vitamin C can get absorbed and transported at each step.

For example, your gut will only absorb enough Vitamin C for critical body functions - such as staving off scurvy. Your gut isn’t going to soak in extra Vitamin C just to maintain supple skin.

Ingested Vitamin C

As we get older, we start losing those capillaries (micro-sized blood vessels that lie just beneath the skin surface) that carry nutrients to every nook and cranny of our skin. Therefore, even less nutrients can reach your skin cells via bloodstream as we age - further diminishing your Vitamin C supply.

Finally, as Vitamin C in the skin fights off free radicals generated by UV rays (and other environmental aggressors, such as second-hand cigarette smoke), Vitamin C is depleted from the skin at a faster rate than in other organs.

Think of your skin as the pawns in a chess game: the first line of defense against environmental attacks, but also the first to experience wear and tear. This is why it’s vital to keep replenishing your skin with nutrients to continue healing from the wear and tear.

If you apply Vitamin C on your skin, it goes directly to your skin cells. Think of it as skipping the middlemen. It’s just a much more effective, direct way of getting your skin the nutrient it wants.

Direct application is better

NOTE: I’m sure you’re thinking- But wait! What is SVCT? SVCT stands for Sodium Dependent Vitamin C Transporters. Transporters are specialized proteins in our body that help move nutrients and other needed substances to various parts of our bodies.

For now, just remember that Vitamin C is useless unless it can hitch a ride in SVCT. Think of SVCT like USPS or Fedex for Vitamin C in your body. SVCT specializes in moving Vitamin C around your body and delivers it to the ultimate destination - your cells.

You can find more information on how SVCT works in Appendix C.

 

Are there other types of Vitamin C, or should I look specifically for ascorbic acid?

Yes, we think it’s best to stick to ascorbic acid.

Ascorbic acid is the naturally occurring form of Vitamin C. The Vitamin C we find in foods (such as berries, vegetables, etc) is of the ascorbic acid variety. And most importantly, our body can readily utilize ascorbic acid, which is why it is referred to as the most “bioavailable” form of Vitamin C.

Ascorbic acid is best

Other ingredients you might see pitched as Vitamin C - such as ascorbyl phosphate, ascorbyl-palmitate, Tetrahexyldecyl Ascorbate, etc - are a derivative form of Vitamin C, and these cannot be used by our body. These derivatives must first be converted to ascorbic acid in order for our body to use them (bioavailability).

That’s not to say that the Vitamin C derivatives don’t work - just that there is a lack of extensive evidence compared to ascorbic acid. Maybe they work, but why take the chance when there is a sure thing?

In conclusion, ascorbic acid seems to be the safest bet to ensure that you’re getting the Vitamin C benefits you’re looking for.

Furthermore, studies have proven that ascorbic acid, when formulated properly, can penetrate through the skin surface barrier and increase Vitamin C concentrations inside epidermal skin cells. It’s less clear whether Vitamin C derivative formulations can do the same.

  • SVCT is the transporter that makes Vitamin C available to be used by skin cells. SVCT specifically transports ascorbic acid and not the derivative forms of Vitamin C.
  • Therefore, Vitamin C derivatives must first be converted to ascorbic acid via enzymatic processes in order to be uptaken by the SVCT transporters into the cell and used by the cell.
  • Some Vitamin C derivatives - such as magnesium ascorbyl phosphate or ascorbyl-6-palmitate - have been shown to not penetrate skin cells well, which limits their effectiveness. This lack of absorption may be due to inefficient conversion to ascorbic acid (Pinnel et al. 2001) (see the figure below reproduced from Pinnel et al). AA absorbs best

Do I need to look specifically for L-ascorbic acid? Or is just ascorbic acid acceptable?

You definitely want L-ascorbic acid, however there is no need to look specifically for the L form because it’s understood that everyone uses it by default.

FDA regulation specifies that L-ascorbic acid is listed as “ascorbic acid” in ingredient lists. Technically, it’s a violation for a brand to put “L-ascorbic acid” in the ingredient list.

But if you want to be absolutely sure, contact the brand and ask to clarify if they use the L form of ascorbic acid.

You can read more about the L- form of ascorbic acid in Appendix D.

 

Is more Vitamin C better? Should I look for products with a very high Vitamin C concentration?

In our opinion, if you apply the product daily then somewhere between 10 to 20% concentration is plenty to keep your skin cells well supplied with Vitamin C.

Interestingly, your skin might actually absorb less when Vitamin C concentration gets very high. It could be counterproductive when Vitamin C concentration goes above 20%.

We’re aware that there is an arms race of products touting high concentrations of Vitamin C as the selling point. However, calibrating an effective skincare formulation isn’t as simple as just overloading on an ingredient. There are many other factors to account for in formulating an effective skincare product.

In practice, there doesn’t seem to be a huge difference whether Vitamin C concentration is 12%, 15% or 20%. At 15% Vitamin C concentration, your skin can reach saturation after 3 days of consistent application (Pinnel et al. 2001), and at that point, you can maintain it with a consistent, daily application. 

too much Vit C is not good

 

How often and when should I apply?

We recommend applying Vitamin C twice daily. This is because the level of Vitamin C in your skin is constantly being depleted 24 hours a day, day and night.

However, if your routine allows for just one application a day, then we recommend using Vitamin C as part of your morning routine. That way you start the day with the highest Vitamin C level as you face the environmental aggressors (UV rays, pollution, etc).

During the day, your Vitamin C level is steadily depleted as Vitamin C is used to mop up free radicals. And while you sleep, Vitamin C is further depleted to fuel the heal and rebuild cycle of your skin.

So, the key is that you regularly replenish Vitamin C in your skin to keep fueling that protect -> heal -> rebuild cycle.

There isn’t a one size fits all on exactly how much to apply as lifestyle affects the rate of Vitamin C depletion. We recommend applying just a thin layer to coat your skin evenly up to twice a day. That should be plenty to keep the level of Vitamin C high in your skin tissue.

Make sure to cleanse your skin before applying Vitamin C to maximize the chance the product you apply can actually get through the skin surface barrier.

Most importantly, always combine your Vitamin C with a good broad spectrum sunscreen for a more complete photoprotection in the morning. Sunscreens and antioxidants work by different mechanisms, so they are supplemental to one another (Lin et al. 2005).

 

Should Vitamin C be used when people have rosacea or acne?

Vitamin C can very well be beneficial to those with rosacea and/or acne due to its anti-inflammatory, wound-healing and scar-prevention benefits.

That being said, the formulation necessary for Vitamin C serums might not necessarily be optimal for sensitive skin because the low pH can be potentially irritating for those skin types.

Ultimately, our recommendation is to use a Vitamin C serum if your skin can tolerate it, but to discontinue use if irritation occurs. Simple as that.

 

What are the drawbacks of Vitamin C?

As every rose has its thorn, so does Vitamin C.

Ascorbic acid can cause potential skin sensitivity, has a shorter shelf life than many other skincare ingredients due to its delicate nature, and typically does not have the most pleasant scents associated with it.

Ascorbic acid serums, assuming they’re well formulated, will have low pH (roughly around the same level of acidity as white wine), which can be irritating for sensitive skin.

Ascorbic acid is also very delicate. An ascorbic acid serum will generally expire in about 2 months of opening (unless you keep it refrigerated). For this reason, Vitamin C serums are not something you want to ration to save up for a long time. If you keep your Vitamin C product in the fridge, that will double its lifespan to about 4 months after opening.

Your Vitamin C serum is fine if the color is in the shade of white wine or apple juice (a light to medium yellow color). Once it gets darker, that means the ascorbic acid in the formula might have broken down and lost its effectiveness, at which point you should switch to a fresh bottle. However, these serums won’t “spoil” or go rancid in a way that becomes harmful to your skin. They would just be ineffective (due to ascorbic acid breaking down).

Finally, ascorbic acid products tend to have an unpleasant scent unless there is added fragrance. If you’re very sensitive to smells, then you might not love applying Vitamin C on your face.

The products you see on the market that contain derivative forms of Vitamin C are created to address one or more of these drawbacks of ascorbic acid, and not necessarily because those derivatives are better for the skin than ascorbic acid.

 

Final thoughts

To recap, Vitamin C is an extensively studied and proven ingredient that protects, heals and rebuilds your skin. Vitamin C can also reduce hyperpigmentation and brighten your skin tone.

If you aspire to achieve or maintain healthy and glowing skin, Vitamin C is one of the cornerstone ingredients you should have in your skin care routine. Make sure the Vitamin C product you pick meets this minimum checklist :

  1. 10% or higher ascorbic acid
  2. Addition of Vitamin E and other antioxidants
  3. Acidic formulation of pH 3.5 or below

The best product is the one you’d actually use, so find a product that you enjoy using and stick to it regularly. As your doctor would tell you, adherence and consistency are the key to achieving success and retaining good results for the long run.

 

Why we wrote this

There is so much information about skin care on the internet, and it can be overwhelming to figure out what to believe.

We wanted to summarize the main, validated scientific findings on the what and the how of beneficial skincare ingredients in a deep, but fun and easy to understand manner. That way, you'll be informed about how skincare ingredients and products work. You’ll also be empowered to filter information and have more productive conversations with your physician.

This writeup is not a sales pitch but is meant to provide you with helpful information that can be verified with widely available public information. So, there are no mentions of any proprietary research or specific product recommendations.

 

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Appendix A - Free radicals and skin health

When UV radiation hits the skin, the photon of radiation interacts with trans-urocanic acid and oxygen in skin to generate reactive oxygen species (ROS) such as singlet oxygen (1O2) and superoxide anion (O2−•), which sets off a chain reaction resulting in the creation of other ROS (Hansen and Simon 1998, Herrling et al. 2007, Kaz ́mierczak-Baran ́ska et al. 2020, Poljsak and Dahmane 2012) (See the figure below, reproduced from Mittler 2017).

 ros cascade

ROS and their free radical cascades destroy proteins, lipids (leading to lipid peroxidation), and nucleic acids and signal cell death (apoptosis) in the skin. ROS act like ricocheting bullets - damaging collagen, the extracellular matrix of the dermis, and cellular DNA – leading to solar elastosis and skin cancer. ROS also induce collagenases (enzymes which breakdown collagen) and together lead to photoaged skin (Hansen and Simon 1998, Herrling et al. 2007).

ROS scavenging molecules, known as antioxidants, are prevalent in skin and the main ones are Vitamin C (for the watery cytosol) and Vitamin E (for the fatty lipid layers). Antioxidants like Vitamin C work by donating electrons to neutralize free radicals (Telang 2013, Pullar et al 2017, Traikovich 1999; Lin et al 2005, Kaz ́mierczak-Baran ́ska et al. 2020).

As the most plentiful antioxidant in the skin, Vitamin C prevents lipid peroxidation and protects the keratinocyte from apoptosis – all signs of skin protection (Pullar et al. 2017; Telang 2013, Traikovich 1999). Vitamin C as an antioxidant serves as an anticancer agent (Nusgens et al. 2001).

Vitamin C is equally effective against harmful effects from both UVB and UVA. UVA penetrates deeper into the skin and damages dermis contributing to collagen breakdown and melanoma formation, while UVB damages epidermis contributing to epidermal mutations, skin cancer, and sunburn (Lin et al. 2005; Telang 2013, Traikovich 1999).  Both UVA and UVB will lead to premature aging of skin - lines, wrinkles, spots and sagging.

Glycosaminoglycan synthesis as part of extracellular matrix formation is increased by Vitamin C, and Vitamin C may also influence gene expression of antioxidant enzymes involved in DNA repair. Vitamin C hence has been shown to increase repair of oxidatively damaged bases (Pullar et al. 2017).

 

Appendix B - Ascorbic acid and skin barrier penetration

The visible skin surface of your skin is called the stratum corneum. This outermost skin barrier is about the same thickness as a sheet of printer paper.

The stratum corneum is 15-20 layers of flattened cells that contain keratin and are further embedded in a lipid matrix of ceramides, cholesterol, and fatty acids. This structure makes the stratum corneum much less permeable and is hence, a protective barrier that wraps our bodies. Think of stratum corneum like a thin wetsuit for your body.

Water-fearing (hydrophobic) molecules that are typically lipophilic (fat-loving) are nonpolar (have no ionic charge) and can diffuse through the stratum corneum, while water-loving (hydrophilic) molecules have an ionic charge, which makes them easily dissolve in water but also makes them impermeable through the stratum corneum.

However, even for hydrophilic molecules such as Vitamin C, when in solution, they can exist in unionized (nonpolar) and ionized (polar) forms while in solution, and at the pH of its pKa, exists in 50% ionized and 50% unionized forms.

Unionized, nonpolar forms, like lipophilic compounds, can pass through the stratum corneum. 

The pH of the formulation should be 3.5 or lower. At this pH, Vitamin C is protonated and uncharged and this both stabilizes Vitamin C in solution and additionally allows it to be in a form that transports well across the stratum corneum (Pinnel et al. 2001; Lin et al. 2005) (See the figure below reproduced from Pinnel et al).

Ascorbic acid penetrates skin better at lower pH

Vitamin C at neutral pH cannot pass the stratum corneum. Ascorbic acid is polar, and hence, hydrophilic in water at a neutral pH. The stratum corneum does not allow any polar particles through. It only allows nonpolar particles through. Hence, lipophilic molecules, which are nonpolar, can go through the stratum corneum.

The trick is that if pH goes below the pKa of a compound, the Vitamin C in solution will lose its charge and be mostly in the nonpolar form. Hence, at a low pH below 3.5, Vitamin C is nonpolar and acts like a lipophilic particle and slips through the stratum corneum. Once through that barrier, it can now be uptaken by the SVCT receptors in the epidermis (otherwise, the epidermis has to steal Vitamin C from the dermis which gets it from the bloodstream).

With a serum, you are getting a L-ascorbic acid which is hydrophilic versus a lipophilic cream that has some other lipophilic version of Vitamin C that even though it passes through the stratum corneum, hasn’t necessarily been shown to work if not converted to ascorbic acid enzymatically. No formulations have been as extensively studied and proven to be effective as those with L-ascorbic acid in water based solution.

 

Appendix C - How Vitamin C gets uptaken by your skin cells

In order for a skincare ingredient to truly deliver its full benefit, it needs two levels of absorption. First, it needs to be able to get past the water-proof outer barrier of the skin (penetrate through the stratum corneum, the skin surface barrier) as discussed above in considerations of pH.

Second, after getting past the stratum corneum the ingredient then needs to be able to get absorbed into skin cells in order to be utilized as nutrients. Scientists call this process of absorption of a substance by cells an “uptake.”

SVCT works at the second level where it helps “transport” Vitamin C inside skin cells so the cells can utilize Vitamin C as a nutrient. In other words, SVCT enables ascorbic acid uptake by skin cells.

SVCT also enables absorption of Vitamin C from your stomach and intestines into the bloodstream as well as transporting Vitamin C out of the bloodstream into appropriate body tissues.

First, there is a limited amount of Vitamin C that can enter into the bloodstream irrespective of how much one ingests because it is limited by the amount of uptake by the Vitamin C transporters in the gut. Major bottleneck is the availability of SVCT transporters each step of the way.

Your body doesn’t need much Vitamin C for essential functions (such as fending off scurvy) so you won’t necessarily absorb as much Vitamin C as you ingest. The intestines have a limited ability to absorb vitamin C.

Studies have shown that absorption of vitamin C decreases to less than 50% when taking amounts greater than 1000 mg. In generally healthy adults, megadoses of vitamin C are not toxic because once the body’s tissues become saturated with vitamin C, absorption decreases and any excess amount will be excreted in urine.

Likewise in the topical application context, it is not possible to go beyond saturation. Your Vitamin C transporters will not transport beyond saturation, and basically, the worst thing you can do is waste product. Your skin will not be harmed even if you applied Vitamin C too much or too often.

Even high doses of dietary Vitamin C have limited impact on blood stream levels as the absorption relies on transporters in the gut. This is why topical Vitamin C is favored in dermatology (Lin et al 2005, Telang 2013).

Delivery of Vitamin C to skin via SVCT

Dermis, the deeper layer of skin, can get vitamin C from the micro blood vessels that penetrate all throughout dermis.

But epidermis, the skin surface layer, does not have direct access to the bloodstream. So it's most effective to directly administer vitamin C to the epidermis by applying vitamin C on the skin.

The epidermis (outermost layer) and dermis have dedicated transporter types specifically for Vitamin C (see the figure above: Delivery of Vitamin C to skin. SVCT = Sodium Dependent Vitamin C Transporters. Reproduced from Pullar et al. 2017).

The dermis transporters can pull Vitamin C into the skin from the bloodstream but the epidermis depends on diffusion from the dermis unless it receives it from topical application. Dietary Vitamin C alone in the bloodstream can lead to a deficiency of Vitamin C in the epidermis particularly with aging. Further, UV exposure depletes Vitamin C from the epidermis. Several reports indicate Vitamin C levels are lower in aged and/or photoaged skin (Pullar et al. 2017).

 

Appendix D - More about ascorbic acid and its chiral forms

There are two isomers of Ascorbic Acid (L as in 'levo' and D as in 'dextro'). See the figure below. The thick triangles are the molecule sticking out at you and the hashed lines are the molecule going into the page. The configurations are different. The differences can be seen more clearly in 3-D models, but 2-D is what we have to work with here.

chiral forms of ascorbic acid

The reason you want L-ascorbic acid goes back to the SVCT transporters.

You need transporters to get the hydrophilic Vitamin C into the cells or else it will not work and both of the primary Vitamin C transporters (SVCT1 and SVCT2) show much greater affinity for the L- rather than the D- form.

So that's why you need the L- form because SVCT transporters don't have good affinity for the D-form (Carr and Vissers 2013).

You sometimes get the "R" and "S" nomenclature for enantiomers of a chiral compound with R = right or clockwise, and S = sinister which means left in latin or counterclockwise.

 

References

Carr AC and Vissers MCM (2013). “Synthetic or Food-Derived Vitamin C - Are they equally bioavailable?” Nutrients 5: 4284-4304.

De Dormael R, Bastien P, Sextus P, Gueniche A, Ye Daniel, Tran C, Chevalier V, Gomes C, Souverain L, Tricaud C (2019). “Vitamin C Prevents Ultraviolet-induced Pigmentation in Healthy Volunteers: Bayesian Meta-analysis Results from 31 Randomized Controlled versus Vehicle Clinical Studies.” J Clin Aesthet Dermatol. 12(2): E53-E59.

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