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Photodermatol Photoimmunol Photomed. 2022;38:459–464.  | 459wileyonlinelibrary.com/journal/phpp
1  |  INTRODUC TION
Acne vulgaris is a common chronic inflammatory skin disease that 
mainly occurs in adolescents. Currently, topical antibiotics and reti-
noids are used as the first- line treatment of mild- to- moderate acne 
vulgaris, but the side effects of retinoids, such as teratogenicity, 
dryness of the skin and mucous membranes, desquamation, muscle 
pain,1 and the more commonly observed drug resistance related to 
antibiotics,2 have limited their clinical application. Phototherapy, in-
cluding red and blue light therapy, intense pulsed light (IPL) therapy, 
laser therapy, and photodynamic therapy (PDT), was developed to al-
leviate the side effect and increase the effectiveness. Light- emitting 
diode (LED) red and blue light have been officially approved for the 
treatment of mild- to- moderate acne vulgaris by the FDA in 2009, 
and it is also recommended for the treatment of moderate acne vul-
garis by the acne guideline in China.3 The therapeutic effect of red 
Received: 6 September 2021  | Revised: 10 December 2021  | Accepted: 27 December 2021
DOI: 10.1111/phpp.12769 
O R I G I N A L A R T I C L E
Comparison of red light and blue light therapies for mild- to- 
moderate acne vulgaris: A randomized controlled clinical study
Jiahua Li | Jiandan Li | Linglin Zhang | Xiaojing Liu | Yajing Cao | Peiru Wang  | 
Xiuli Wang
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Jiahua Li and Jiandan Li are Co- first authors. 
Institute of Photomedicine, Shanghai Skin 
Disease Hospital, School of Medicine, 
Tongji University, Shanghai, China
Correspondence
Peiru Wang and Xiuli Wang, Institute of 
Photomedicine, Shanghai Skin Disease 
Hospital, School of Medicine, Tongji 
University, Shanghai 200092, China.
Emails: wangpeiru@tongji.edu.cn (PW); 
wangxiuli_1400023@tongji.edu.cn (XW)
Funding information
This work was supported by the 
National Natural Science Foundation of 
China under Grant number 81803158, 
81903241, and the Emerging Frontier 
Technology Project of Shanghai Shenkang 
Hospital Development Center under Grant 
number SHDC12019130
Abstract
Background: Red and blue light therapies are safe and effective treatments for mild- 
to- moderate acne vulgaris. However, very few previous studies have directly com-
pared the characteristics of these two methods.
Objective: To compare the efficacy and side effects of red light (RL) and blue light 
(BL) for acne vulgaris and to assess these two therapies in different types of lesions.
Materials and Methods: A total of 28 subjects with mild- to- moderate acne vulgaris 
were randomized into the RL group or the BL group. Subjects in each group received 
different light treatments, and they were followed up regularly until 2 weeks after the 
last treatment. The improvement rates of different types of acne lesions were com-
pared between the 2 groups, as well as the incidence of adverse reactions.
Results: At the 2- week follow- up, the average improvement rate of total acne lesions 
was 36.2% in the RL group and 30.7% in the BL group (p > .05). The average improve-
ment rate of inflammatory and non- inflammatory lesions was 51.5% and 17.3% in the 
RL group, compared with 26.4% and 10.0% in the BL group (all p > .05). Treatment- 
related adverse reactions were observed distinctly in the BL group.
Conclusions: Red light and BL therapies have similar efficacy in mild- to- moderate 
acne vulgaris, especially for inflammatory lesions. RL had advantages with fewer ad-
verse reactions compared with BL.
K E Y W O R D S
acne vulgaris, blue light, LED, red light
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mailto:
https://orcid.org/0000-0003-0006-4269
mailto:
mailto:wangpeiru@tongji.edu.cn
mailto:wangxiuli_1400023@tongji.edu.cn
http://crossmark.crossref.org/dialog/?doi=10.1111%2Fphpp.12769&domain=pdf&date_stamp=2022-01-19
460  |    LI et aL.
light (RL) on acne is considered to be mediated by photobiomodula-
tion (PBM), thus playing a role in anti- inflammation and promoting 
skin recovery.4,5 Blue light (BL) therapy for acne mainly acts through 
an endogenous photodynamic reaction, which has a broad- spectrum 
inhibitory effect on bacteria, such as C. acnes.6
At present, there is still no unified consensus on the treatment 
regime for mild- to- moderate acne vulgaris with RL and BL. Studies 
comparing the two lights directly are lacking, which makes their re-
spective characteristics in the treatment, such as the efficacy on 
various types of acne lesions, unclear. In this study, we aimed to 
compare the efficacy and safety of LED RL and BL in treating mild- 
to- moderate acne vulgaris and help the clinicians to optimize the 
treatment for acne vulgaris patients.
2  |  MATERIAL S AND METHODS
2.1  |  Study design
This study was designed as a 6- week, prospective, randomized con-
trolled clinical study that compared the efficacy and safety between 
RL and BL in the treatment for mild- to- moderate acne vulgaris. 
According to a random number table, all enrolled subjects were ran-
domly assigned into either the RL or BL group. The subjects were 
scheduled to receive a 4- week course of treatment, 3 treatments 
per week, and a follow- up visit at 2 weeks after the final treatment.
This study was approved by the Ethics Committee of Shanghai 
Dermatology Hospital (2018– 21(ke)). Informed consent was ob-
tained from all subjects before enrollment.
2.2  |  Subject enrollment
Subject enrollment and informed consent were performed in the 
outpatient department of Shanghai Dermatology Hospital from July 
2019 to August 2020.
The main inclusion criteria were as follows: (1) Male or female 
patients aged ≥13 years. (2) Patients diagnosed with grade I– III acne 
vulgaris according to the Pillsbury Scale.7
The main exclusion criteria were as follows: (1) Photosensitivity or 
taking photosensitizer drugs. (2) Received topical or systemic treat-
ment with antibiotics or tretinoin within 1 month. (3) Received corti-
costeroids, immunosuppressants, or other acne- influencing drugs in 
2 weeks. (4) Pregnancy or lactation. (5) Having serious systemic dis-
eases refer to malignant tumors, cardiovascular and cerebrovascular 
diseases, and other diseases that cannot tolerate red and blue light 
treatment or other skin diseases at the treatment site (face).
2.3  |  Devices and treatment protocols
Omnilux Revive (manufactured by GlobalMed Technologies Co.) 
equipped with RL or BL devices was applied in this study. In the 
RL group, apparatus generating LED- RL with a wavelength of 
633 ± 10 nm, power density of 80 mW/cm ², distance of 10– 15 cm, 
and total energy density of 96 J/cm² was used. With the BL mode, 
LED- BL with a wavelength of 415 ± 10 nm, power density of 
40 mW/cm², distance of 5– 10 cm, and total energy density of 48 J/
cm² was used.8 RL or BL was illuminated for 20 min for the whole 
face. Goggles were worn during the treatment to protect the retina 
from damage.
2.4  |  Efficacy assessments
VISIA skin analysis system (manufactured by Canfield Ltd.) was used 
to collect subjects’ facial photographs before the 1st, 4th, 7th, 10th, 
and 12th treatments and at the 2- week follow- up. During each infor-
mation collection, high- definition facial photographs of the subjects’ 
frontal face, left 45- degree side face, and right 45- degree side face 
were taken in a fixed position and fixed distance with white light.
Among them, high- definition photographs of the face were used 
to evaluate therapeutic efficacy. First, accordingto the photographs, 
objective assessments of acne severity were conducted by two der-
matologists not involved in treatments, using the method of acne 
lesion classification count, by which the acne lesions of subjects 
were classified into inflammatory lesions (papules, pustules, or nod-
ules) and non- inflammatory lesions (comedones). Second, the acne 
lesion improvement rate of each subject was calculated using the 
following formula: improvement rate = (number of lesions before 
therapy - number of lesions after therapy) / number of lesions before 
therapy × 100%. Third, the efficacy evaluation of each subject was 
assessed according to the A. R. Shalita's standard.9 Finally, the effec-
tive rate in the RL or BL group was calculated individually using the 
following formula: effective rate = (number of cured cases + num-
ber of significantly effective cases + number of effective cases) / 
number of cases in group × 100%. The effective rate and improve-
ment rate of total, inflammatory, and non- inflammatory acne lesions 
were compared between the RL and BL groups. During therapy, the 
variations in skin color were observed to assess the effects on color 
mediated by RL or BL.
2.5  |  Adverse effect
Occurrence, severity, and duration of objective symptoms, like er-
ythema or scaling, observed and other subjective complained dis-
comforts were evaluated and recorded at each visit. All evaluations 
and recordings of adverse events were conducted by the same re-
searcher who did not participate in treatments.
2.6  |  Statistical analysis
Statistical analysis was conducted using the Statistical Package for 
the Social Sciences (SPSS) version 25.0 software (IBM Corporation). 
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    |  461LI et aL.
The paired t- test or Wilcoxon signed- rank test was performed 
to analyze the variations in acne lesion counts in each group. The 
independent- samples t- test or Mann– Whitney U test was used to 
compare the acne lesion improvement rate between the RL and BL 
groups. A two- sided Fisher exact test was performed for compar-
ing the effective rate between the two groups. To reduce the bias 
of study results, a multiple interpolation method or mean imputa-
tion was performed to process the missing quantitative data and 
qualitative data, respectively.10 p < .05 was considered statistically 
significant.
3  |  RESULTS
3.1  |  Patient characteristics
Of the 116 patients who were screened, 28 patients were eligible 
for this study and were equally randomized into 2 groups (Figure 1). 
The characteristics of the participants can be found on Table 1. The 
RL group included 2 males and 12 females; the BL group included 
3 males and 11 females. The Fitzpatrick skin Type of subjects was II 
to IV. The mean age in the RL group was 24.9 ± 2.8 years (range, 17– 
28 years); the mean age in the BL group was 26.7 ± 5.8 years (range, 
17– 35 years). In the RL group, there were 9 subjects with Pillsbury 
Grade I, 4 with Grade II, and 1 with Grade III; there were 7 subjects 
with grade I, 5 with grade II, and 2 with grade III in the BL group. 
There were no statistically significant differences in mean age, gen-
der composition of subjects, skin type, and acne severity at baseline 
between the two groups.
3.2  |  The improvement rate of different types of 
lesions after RL is comparable to that after BL
At the 2- week follow- up, the average improvement rate of total acne 
lesions was 36.2 (±27.3)% in the RL group and 30.7 (±33.2)% in the 
BL group; however, the difference between the 2 groups was not 
statistically significant (p = .636). The average improvement rate of 
inflammatory acne lesions was 51.5 (±28.8)% in the RL group and 
26.4 (±63.7)% in the BL group, but the difference between the two 
groups was not statistically significant (p = .187). The average im-
provement rate of non- inflammatory acne lesions was 17.3 (±42.9)% 
in the RL group and 10.0 (±49.9)% in the BL group, which was also 
not statistically different (p = .890) (Figure 2).
3.3  |  The effective rate of acne vulgaris after RL is 
similar to that after BL
According to the A. R. Shalita standard, 7 effective cases, 4 improved 
cases, 2 ineffective cases, 1 aggravated case, and no cured or signifi-
cantly effective case were observed in the RL group. The effective 
rate of RL was 50.00%. In the BL group, there were 0 cured cases, 
1 significantly effective case, 4 effective cases, 3 improved cases, 
4 ineffective cases, and 2 aggravated cases. The effective rate of 
BL was 35.71%. The effective rate of acne vulgaris in the RL and BL 
groups is shown in Table 2. There was no statistical difference in the 
effective rate between the two groups (p = .704). Figure 3 shows the 
improvement of acne lesions in both groups.
3.4  |  Adverse effects and skin pigmentation
No treatment- related adverse reactions were observed in the RL 
group, while 3 subjects (21.43%) with mild skin dryness, desquama-
tion, or itching were observed in the BL group. Among them, 1 sub-
ject had experienced dryness and desquamation 3 times (after the 
1st, 2nd, and 6th treatments), 1 subject had reported skin itching, 
dryness, and desquamation at the 1st treatment, and another 1 sub-
ject had experienced dryness on both cheeks after the 3rd treatment. 
All of the above- mentioned adverse reactions were mild and toler-
able. Skin dryness and desquamation were relieved within a few days. 
Skin itching was a transient discomfort, and it was relieved in the mid-
dle of the treatment. Skin pigmentation was observed distinctly in the 
BL group compared to the RL group (Figure 4). No case of secondary 
scarring or infection was observed throughout the study.
F I G U R E 1  Flow chart. RL, red light; BL, 
blue light
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462  |    LI et aL.
4  |  DISCUSSION
Although there are many clinical studies of RL and BL in treating 
acne vulgaris, most of them are about "combined application of RL 
and BL" or "application of RL or BL alone." There is no clinical study 
that directly compares RL and BL therapies, and only limited data 
are available on the efficacy and safety of these methods. The best 
indication for RL and BL is unclear, which creates some confusion in 
the clinical application of red and blue light therapies for acne vul-
garis in dermatology.
In this study, both RL and BL showed a therapeutic effect on 
mild- to- moderate acne vulgaris. More specifically, RL showed a sat-
isfactory therapeutic effect in the treatment of inflammatory acne 
lesions. In terms of that, the improvement rate in the RL group was 
more than 50%. However, the effects on non- inflammatory acne le-
sions were not that ideal in both groups. The results of our study are 
different from those of Na's,11 in which both inflammatory and non- 
inflammatory skin lesions were improved after RL therapy.
Moreover, it seems that BL had a faster onset than RL, while the 
therapeutic effect of RL lasted longer (Figure 2). It was observed 
that before the 2nd week, the improvement rate in the BL group was 
higher than that in the RL group, but after that, RL started to catch 
up with BL. After the 4th week, when all treatments had already 
been conducted, compared to the decrease in the BLgroup, the im-
provement rate in the RL group still maintained an upward trend. 
The factor that may have accounted for this phenomenon is that 
the primary therapeutic mechanism of BL is anti- C. acne through 
an endogenous photodynamic reaction, which means that as long 
as BL starts, the therapeutic effect would be produced, but when 
the treatment is terminated, the anti- C. acne effect may also end.12 
Therefore, despite the faster onset observed in the BL group, the 
4- week course of treatment could not maintain the efficacy well, 
and it may require a longer course of BL treatment to achieve a bet-
ter effect. However, the anti- inflammation and skin barrier recovery 
effects of RL on acne vulgaris were mediated by PBM, which could 
induce various changes in the intercellular signaling pathway13; thus, 
it may have a slower onset but may last longer. In clinical practice, 
when we combine RL and BL in the treatment of acne vulgaris, BL 
can be used first to ensure faster efficacy.
In terms of side effects, both RL and BL were safe in our study, 
with a few mild adverse reactions observed in the BL group and no 
case of adverse reaction observed in the RL group. The most com-
mon adverse reactions of BL reported in the previous study14 are 
skin dryness, desquamation, and itching. Usually, the symptoms 
are mild and transient, which will not cause severe discomfort and 
could be relieved without taking any other treatments. However, 
ophthalmological studies showed that myopia could be caused by 
RL exposure,15 which still has not drawn enough attention from 
dermatologists. Also, there are pieces of evidence of retina damage 
caused by BL exposure.16 Therefore, very stringent eye protection 
measures are needed after RL and BL therapies. In the East Asian 
area, female patients worry that their facial skin color would become 
darker after taking the RL or BL therapy. Our results showed that 
obvious pigmentation was observed in the BL group. Previous basic 
TA B L E 1  Baseline characteristics of subjects in the RL group and 
BL group
RL group BL group p- Value
Sample size, n 14 14 - 
Sex, n (M/F) 2/12 3/11 .622
Age, years (M ± SD) 24.9 ± 2.8 26.7 ± 5.8 .306
Skin phototype, n (II/
III/IV)
2/8/4 1/9/4 .822
Pillsbury Grade, n (I/
II/III)
9/4/1 7/5/2 .819
Abbreviations: BL, blue light; RL, red light.
F I G U R E 2  Comparison of average improvement rates of (A) total lesions, (B) inflammatory lesions, and (C) non- inflammatory lesions 
between the RL group and BL group. No statistical differences (p ≥ .05) between the 2 groups at the 2- week follow- up. BL, blue light; RL, red 
light
TA B L E 2  Effective rate of acne vulgaris in the RL group and BL 
group
Effective rate
RL group 7/14 (50.00%)
BL group 5/14 (35.71%)
p- Value .704
Abbreviations: BL, blue light; RL, red light.
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    |  463LI et aL.
research also showed transient melanogenesis effect in normal skin 
after exposure to BL,17 and we found that the skin color gradually re-
covered after stopping BL therapy. The pigmentation may be related 
to skin phototype in the study because it mainly occurred in subjects 
with skin types III and IV. Regazzetti et al.18 found that blue light- 
induced (5– 90 J/cm2) pigmentation in darker skin types results from 
activation of opsin 3. For the long- term side effects of light ther-
apy, BL can induce oxidative stress preferentially in mitochondria, 
but green, red, far red, or infrared light did not.19 Therefore, longer 
exposure to high- energy blue light can also increase the amount of 
DNA damage, cell and tissue death, and injury, causing skin barrier 
damage, hyperpigmentation, and photoaging.20 Conversely, red light 
is often reported to prevent photoaging,21 but attention needs to be 
paid to the potential harm that long- term exposure to high doses of 
red light.
The limitations of this study are the small sample size and the 
gender ratio imbalance of subjects; females accounted for the vast 
majority (23/28); thus, the conclusions may be more applicable to 
female patients. Besides, the follow- up time of this study was only 
2 weeks; thus, a longer follow- up may be required to observe the 
F I G U R E 3  Photographs of the RL group (A) and BL group (B) at baseline, 2- week, 4- week, and after the 2- week follow- up of the 
treatment. Clinical improvements were observed in both groups. BL, blue light; RL, red light
F I G U R E 4  Pigmentation of subjects at 
each follow- up visit in both the RL group 
and BL group. BL, blue light; RL, red light
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464  |    LI et aL.
long- term efficacy and safety of RL and BL in the treatment of acne 
vulgaris.
To sum up, in our study, both RL and BL were effective for treat-
ing mild- to- moderate acne vulgaris patients, especially for inflam-
matory lesions but ineffective for non- inflammatory lesions. Despite 
the tendency of superiority observed in the RL group, no statistically 
significant difference was found between the RL and BL in terms of 
efficacy. However, considering the maintenance of efficacy and the 
lower incidence of adverse reactions, LED- RL may be a more recom-
mendable therapy than LED- BL for treating mild- to- moderate acne 
vulgaris, which may need a large- scale multi- center clinical trial to 
obtain further confirmation.
ACKNOWLEDG EMENTS
The authors would like to thank the personnel of the "Institute of 
Photomedicine" for their cooperation in this study. We thank LetPub 
for its linguistic assistance during the preparation of this manuscript.
CONFLIC T OF INTERE S T
The authors report no conflict of interest.
AUTHOR CONTRIBUTIONS
All authors contributed to the study's conception and design. Jiahua 
Li conceived and designed the analysis. Material preparation, data 
collection, and paper were performed by Jiahua Li and Jiandan Li. 
Analysis and interpretation of the data were supported by Linglin 
Zhang, Xiaojing Liu, and Yajing Cao. Peiru Wang and Xiuli Wang con-
ducted a critical review of the manuscript, contributing important 
intellectual content. All authors gave final approval of the version 
for publication.
DATA AVAIL ABILIT Y S TATEMENT
The datasets generated and/or analyzed during the current study 
are available from the corresponding author on reasonable request.
ORCID
Peiru Wang https://orcid.org/0000-0003-0006-4269 
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How to cite this article: Li J, Li J, Zhang L, et al. Comparison of 
red light and blue light therapies for mild- to- moderate acne 
vulgaris: A randomized controlled clinical study. Photodermatol 
Photoimmunol Photomed. 2022;38:459– 464. doi:10.1111/
phpp.12769
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https://doi.org/10.1111/phpp.12769
https://doi.org/10.1111/phpp.12769
	Comparison of red light and blue light therapies for mild-­to-­moderate acne vulgaris: A randomized controlled clinical study
	Abstract
	1|INTRODUCTION
	2|MATERIALS AND METHODS
	2.1|Study design
	2.2|Subject enrollment
	2.3|Devices and treatment protocols
	2.4|Efficacy assessments
	2.5|Adverse effect
	2.6|Statistical analysis
	3|RESULTS
	3.1|Patient characteristics
	3.2|The improvement rate of different types of lesions after RL is comparable to that after BL
	3.3|The effective rate of acne vulgaris after RL is similar to that after BL
	3.4|Adverse effects and skin pigmentation
	4|DISCUSSION
	ACKNOWLEDGEMENTS
	CONFLICT OF INTEREST
	AUTHOR CONTRIBUTIONS
	DATA AVAILABILITY STATEMENT
	REFERENCES

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