What Really Works for Dark Spots? A Clinical Study Offers Clues
A clinical study compared a hydroquinone-free formula containing tranexamic acid, niacinamide, vitamin C and arbutin with 4% hydroquinone. What did the researchers discover?
Sun spots, acne marks and melasma can appear easily, but improving their appearance often takes time. This is because a dark spot is not simply a mark sitting on the surface of the skin. It develops when the skin produces more pigment in one area than it normally would.
Hydroquinone is one of the best-known ingredients used to treat hyperpigmentation. Although it can be effective, it may also cause redness, dryness, burning or irritation in some people.
Could a formula without hydroquinone provide similar results with less irritation?
A small clinical study published in 2020 compared 4% hydroquinone with a hydroquinone-free formula containing tranexamic acid, niacinamide, vitamin C, arbutin, epidermal growth factor and other ingredients.
The results were encouraging. After one month, the hydroquinone-free formula was rated more favourably for the overall appearance of hyperpigmentation and was better tolerated by the participants.
However, this does not mean hydroquinone is no longer useful or that every product containing these alternative ingredients will produce the same results. To understand what the study really tells us, we must also examine its limitations.
Why do dark spots develop?
Melanin is the natural pigment that gives our skin its colour. It also helps protect the skin from the effects of sunlight.
You can think of melanin as part of the skin’s natural defence system. However, sun exposure, inflammation, hormonal changes or skin injuries can cause certain areas to produce more melanin than usual. These areas then appear darker than the surrounding skin.
This condition is called hyperpigmentation, which simply means that some areas of the skin have developed more colour.
Common causes include:
- Sun exposure
- Acne
- Skin irritation or injury
- Hormonal changes
- Melasma
- Certain medications
- Age-related sun spots
Not every dark spot has the same cause. For this reason, the most suitable skincare or treatment may differ from one person to another.
What is hydroquinone?
Hydroquinone is a powerful ingredient used to reduce the appearance of dark spots.
The skin uses several enzymes when producing melanin. Enzymes can be thought of as tiny helpers that perform specific jobs in the skin. One of these enzymes is called tyrosinase.
Hydroquinone slows the activity of tyrosinase and can therefore reduce the production of new pigment. It may be used to treat:
- Melasma
- Sun spots
- Dark marks left after acne
- Pigmentation following inflammation or skin injury
Hydroquinone is not an ordinary moisturizing ingredient. It is a strong active treatment, particularly when used at a concentration of 4%.
Possible unwanted effects include:
- Redness
- Dryness
- Burning
- Itching
- Irritation
- Increased sensitivity
Incorrect or prolonged use may rarely cause a more serious blue-black discolouration known as exogenous ochronosis. For this reason, higher-strength hydroquinone should be used under the guidance of a qualified healthcare professional and with proper sun protection.
What question did the researchers ask?
The researchers wanted to answer a straightforward question:
Could a formula containing several skin-brightening ingredients provide results similar to or better than 4% hydroquinone without causing as much irritation?
They tested a proprietary formula called SKNB19. Its featured ingredients included:
- Tranexamic acid
- Niacinamide
- Vitamin C
- Arbutin
- Epidermal growth factor
- Other supporting ingredients
These substances do not all work in the same way. Some may influence pigment production, while others may affect how pigment is transferred between skin cells or support the skin barrier and renewal process.
The researchers wanted to determine how these ingredients performed when used together in one complete formula.
How was the study conducted?
The study included 18 adults with facial hyperpigmentation.
Each participant applied:
- The hydroquinone-free SKNB19 formula to one side of the face
- A 4% hydroquinone product to the other side
The side assigned to each product was selected randomly. This helped reduce the risk of researchers consciously or unconsciously choosing one side for a particular treatment.
The hydroquinone-free formula was applied twice a day, in the morning and evening. The 4% hydroquinone product was applied once each evening.
Three-dimensional facial images were taken before treatment began and again one month later.
The results were assessed in two ways:
- Participants rated changes in their overall appearance, redness, irritation and how well they tolerated each product.
- Five independent reviewers compared the before-and-after images. The group included two dermatologists, two facial plastic surgeons and one oculoplastic surgeon.
Comparing two products on opposite sides of the same person’s face can be useful. Age, genetics, skin type and lifestyle are the same on both sides, which reduces some of the differences that arise when comparing two separate groups of people.
What happened after one month?
According to the researchers, the hydroquinone-free formula significantly improved the overall appearance of hyperpigmentation.
In the participants’ self-assessments:
- The side treated with SKNB19 was rated 28.5% better than the side treated with hydroquinone.
In the independent reviewers’ assessments:
- The SKNB19-treated side was rated 27% better.
- In side-by-side comparisons, 88.2% of the SKNB19-treated sides appeared equal to or better than the hydroquinone-treated sides.
The study also examined how well the products were tolerated:
- The hydroquinone-free formula caused significantly less irritation.
- One participant left the study because of severe intolerance to hydroquinone.
- No participant had to discontinue SKNB19 because of intolerance.
- Participants reported less redness with SKNB19, although the difference was not strong enough to be considered statistically significant.
What does “27% better” really mean?
This result can easily be misunderstood.
It does not mean that 27% of every dark spot disappeared. It also does not mean that the participants’ skin became 27% lighter.
The participants and independent reviewers gave scores based on the overall appearance of each side of the face. When these scores were compared, the hydroquinone-free side received more favourable ratings.
A more accurate way to explain the result is:
After one month, the side treated with the hydroquinone-free formula was rated more favourably for the overall appearance of hyperpigmentation than the side treated with 4% hydroquinone.
These percentages apply only to the proprietary SKNB19 formula tested in this study. They cannot automatically be applied to every product containing vitamin C, niacinamide, arbutin or tranexamic acid.
How might the ingredients in the formula work?
Tranexamic acid
Sun exposure, hormones and inflammation can send signals that encourage the skin to produce more pigment. Tranexamic acid may help interrupt some of these signals.
It has been studied particularly for melasma and pigmentation connected with inflammation. Its effect can depend on the concentration, formulation, application method and type of pigmentation being treated.
Niacinamide
Niacinamide is a form of vitamin B3. It may help reduce the transfer of pigment from pigment-producing cells to surrounding skin cells.
Niacinamide can also support the skin barrier—the protective outer layer that helps the skin retain moisture and defend itself against irritation.
This is important because irritated skin may develop new areas of discolouration, particularly in people who are prone to post-inflammatory hyperpigmentation.
Vitamin C
Vitamin C is an antioxidant that helps protect the skin against environmental stress. It may also influence tyrosinase, the enzyme involved in melanin production.
However, “vitamin C” is not one standard ingredient. A product’s performance depends on:
- The form of vitamin C
- Its concentration
- The formula’s pH
- Its stability when exposed to light and air
- How effectively it reaches the skin
Two products labelled “vitamin C” may therefore perform very differently.
Arbutin
Arbutin may help slow the activity of tyrosinase and reduce excess pigment production.
Although arbutin is chemically related to hydroquinone, it is not the same substance. Its effectiveness depends on the type of arbutin used, its concentration, purity and stability within the finished product.
Epidermal growth factor
Epidermal growth factor is associated with communication between skin cells and the skin’s renewal processes. It is not usually described as a traditional pigment-reducing ingredient.
Because all the ingredients were tested together, the study does not show how much epidermal growth factor—or any single ingredient—contributed to the final result.
Does this study show that hydroquinone is ineffective?
No.
Hydroquinone remains an effective treatment for certain forms of hyperpigmentation. However, because it is a powerful active ingredient, it may also cause irritation or other unwanted effects.
The study compared only one particular hydroquinone-free formula with 4% hydroquinone. Its findings can be summarized as follows:
In this small group of participants, the tested hydroquinone-free formula performed as well as or better than 4% hydroquinone after one month and caused less irritation.
This does not mean that hydroquinone never works or should never be used. The right option depends on the cause of the pigmentation, the person’s skin and the advice of a qualified healthcare professional.
What were the study’s strengths?
The study had several valuable features:
- Both products were compared on the same person.
- The side assigned to each product was selected randomly.
- Standardized images were taken before and after treatment.
- Five independent medical specialists reviewed the images.
- The researchers assessed irritation, redness and tolerability as well as appearance.
- Participants also reported their own experience with each product.
Tolerability matters because even a powerful product cannot provide consistent results if irritation prevents someone from using it regularly.
What were the study’s limitations?
Although the results were encouraging, several important limitations must be considered.
Only 18 people participated
Eighteen participants form a very small study group. One person also left because of severe intolerance to hydroquinone.
The results cannot automatically be applied to every age group, skin tone or type of hyperpigmentation.
The study lasted only one month
Dark spots often require more than one month of care.
The study does not tell us:
- Whether the results lasted
- Whether the pigmentation later returned
- How the products would be tolerated for several months
- Whether delayed side effects could develop
The products were not applied equally often
SKNB19 was applied twice a day, while hydroquinone was applied once each evening.
The difference in results may therefore have been influenced not only by the formulas but also by how frequently they were used.
The main assessments were based on appearance
Participants and specialists evaluated the overall appearance of the face using rating scales and images.
These observations are useful, but objective measurements—such as a device-based melanin index—could have strengthened the evidence.
The ingredients were not tested separately
Tranexamic acid, niacinamide, vitamin C, arbutin and epidermal growth factor were combined in the same product.
The study does not prove that niacinamide alone is better than hydroquinone or that tranexamic acid alone produced the result. It evaluated the complete proprietary formula.
How does Akita interpret this research?
This study supports an important product-development principle: a skincare product should not be judged by one fashionable ingredient or by the length of its ingredient list.
Hyperpigmentation can involve several processes. A well-designed formula may therefore combine ingredients that work through different pathways. But simply placing several popular ingredients in one product does not guarantee that the finished formula will be effective.
Important questions include:
- Are the active ingredients used at suitable concentrations?
- Do they remain stable in the formula?
- Can they work well together?
- Is the finished product well tolerated?
- Has its safety and stability been evaluated?
- Was effectiveness tested on the finished product or only assumed from individual raw ingredients?
Akita follows a whole-formula approach. In Akita skincare products that require a water phase, ordinary water is replaced with Akita Non-De-Oiled Rose Water. This is part of how the complete formula is developed, rather than treating the water phase as an unimportant filler.
However, the scientific boundary must remain clear: the 27% and 28.5% results belong only to the SKNB19 formula evaluated in this study. They are not results obtained from an Akita product.
Claims about an Akita formula must be based on tests and analyses performed on that specific finished product. The correct way to use outside research is to learn from its formulation principles—not to transfer its percentages to another brand.
Why is sunscreen essential when treating dark spots?
Think of dark-spot care as emptying water from a boat. If water continues to enter while you are removing it, the boat will keep filling again.
A dark-spot product may help improve existing pigmentation, while unprotected sun exposure continues to tell the skin to produce more melanin.
For this reason:
- Use a broad-spectrum sunscreen every day.
- Reapply it when necessary.
- Use shade, hats and protective clothing.
- Avoid combining so many strong active ingredients that the skin becomes irritated.
- Support the skin barrier with an appropriate moisturizer.
Using more products does not always produce faster results. Excessive irritation may make pigmentation worse, especially in people prone to post-inflammatory dark marks.
Can hydroquinone-free formulas be effective alternatives?
This study suggests that a carefully developed formula containing ingredients that work through different pathways may help improve the appearance of dark spots.
After one month, the tested hydroquinone-free formula:
- Improved the overall appearance of hyperpigmentation
- Was rated more favourably than 4% hydroquinone
- Caused less irritation
- Was better tolerated by the participants
However, one small study involving 18 people cannot prove that this formula can permanently replace hydroquinone.
The most accurate conclusion is:
Well-formulated, hydroquinone-free products may offer a promising approach to hyperpigmentation. Their value, however, must be judged through safety, stability and efficacy testing of the complete finished formula—not simply by reading ingredient names on the label.
Frequently Asked Questions
Does hydroquinone bleach the skin?
Hydroquinone is not intended to change a person’s natural skin colour. It reduces melanin production in areas where excess pigment has developed, helping dark spots look more even with the surrounding skin.
Is hydroquinone dangerous?
Hydroquinone can be effective when used appropriately, but it may cause irritation and other unwanted effects. Higher concentrations, including 4%, should be used under professional guidance.
Does this study prove that the hydroquinone-free formula is better?
No. The findings are encouraging, but the study included only 18 participants and lasted one month. Larger and longer studies are needed.
Is niacinamide more effective than hydroquinone?
This study cannot answer that question. Niacinamide was used with several other ingredients and was not tested on its own.
Are arbutin and hydroquinone the same?
No. They are chemically related but are not the same substance. Their effects, strengths and recommended uses differ.
Will every product containing these ingredients provide the same results?
No. Concentration, ingredient quality, pH, stability and the design of the complete formula can all affect performance.
Will combining several dark-spot products give faster results?
Not necessarily. Using too many powerful products at once may damage the skin barrier and cause irritation. That irritation can sometimes make dark marks worse.
Is sunscreen necessary when using a dark-spot product?
Yes. Sun exposure can encourage the skin to produce more pigment. Consistent sun protection is one of the most important parts of any routine for uneven skin tone.
Important: This article is for educational purposes and does not provide a diagnosis or treatment plan. Consult a dermatologist if pigmentation changes rapidly, spreads, does not improve or becomes irritated.
Reference – APA 7
Kalasho, B. D., Minokadeh, A., Zhang-Nunes, S., Zoumalan, R. A., Shemirani, N. L., Waldman, A. R., Pletzer, V., & Zoumalan, C. I. (2020). Evaluating the safety and efficacy of a topical formulation containing epidermal growth factor, tranexamic acid, vitamin C, arbutin, niacinamide and other ingredients as hydroquinone 4% alternatives to improve hyperpigmentation: A prospective, randomized, controlled split face study. Journal of Cosmetic Science, 71(5), 263–290. https://pubmed.ncbi.nlm.nih.gov/33022197/
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