Lasers in Medical Science

https://doi.org/10.1007/s10103-020-03100-4

REVIEW ARTICLE

ILIB (intravascular laser irradiation of blood) as an adjuvant therapy

in the treatment of patients with chronic systemic diseases—an
integrative literature review
Ruan Felipe Ferreira Tomé 1 & Diego Filipe Bezerra Silva 2,3 & Carlus Alberto Oliveira dos Santos 2 &
Gabriella de Vasconcelos Neves 2 & Ana Karina Almeida Rolim 2 & Daliana Queiroga de Castro Gomes 2

Received: 3 May 2020 / Accepted: 7 July 2020

# Springer-Verlag London Ltd., part of Springer Nature 2020

Abstract
To perform an integrative review of the literature on the effectiveness of intravascular laser irradiation of blood (ILIB) as an
adjunct therapy in the treatment of chronic systemic diseases. This is an integrative literature review that included non-
randomized and randomized controlled clinical trials that specifically evaluated the therapeutic effect of ILIB on chronic systemic
diseases, without restriction of time, and written in English. The Medical Publications (PubMed)/MEDLINE database was used.
MeSH (Medical Subject Headings) was used to select search descriptors with the Boolean operators “AND/OR.” After applying
the inclusion and exclusion criteria, 13 articles were selected. Coronary diseases were the most prevalent, followed by type 2
diabetes mellitus, with the coronary artery being the most widely used access route for ILIB application. Despite the varied
parameters and protocols for using this kind of therapy, all studies have shown satisfactory results in the patients’ clinical
condition. ILIB proved to be effective in all organic systems, showing some positive result. However, studies on the effect of
this therapy on various diseases are still scarce in the literature, and there is a need for more well-designed clinical trials to better
understand the role of ILIB in various systemic diseases.

Keywords Low-level light therapy . Blood . Humans . Disease

Introduction oxidase. This is unit IV in the mitochondrial electron transport

For 40 years, low-level laser therapy (LLLT) or
photobiomodulation (PBM) has been used in experimental
and clinical fields as adjuvant therapy. LLLT can stimulate
or inhibit altered biological functions and normalize them
[1]. To generate biological effects, when the laser reaches
the target tissue, it primarily needs to be absorbed. When cells
are irradiated, light is absorbed mainly by cytochrome c
* Diego Filipe Bezerra Silva
diegofilipeb@gmail.com
1 [5]. It has been reported that this treatment is used to accelerate
Faculdades Integradas de Patos, R. Horácio Nóbrega, S/N Belo
Horizonte 58704-000 Brazil
2 modulation [6]. These characteristics are mainly due to the
Post Graduate Program in Dentistry, State University of Paraíba, R.
Baraúnas, 351 – Bairro Universitário Campina Grande PB
58429-500 Brazil
3
Departament of Dentistry, State University of Paraíba, R. Baraúnas,
351 – Bairro Universitário Campina Grande PB Brazil
chain [2], where the third phase of cellular respiration takes
place. After the absorption of photons, there is an increase in
adenosine triphosphate (ATP), a brief burst of reactive oxygen
species, an increase in nitric oxide, and a modulation of calci-
um levels [2].
LLLT can produce reactive oxygen species (ROS) in nor-
mal cells, but when used in oxidatively stressed cells or in
animal models of disease, ROS levels are lowered. PBM is
able to up-regulate antioxidant defenses and reduce oxidative
stress. One of the most reproducible effects of LLLT is an
overall reduction in inflammation, which is particularly im-
portant for various disorders like inflammation in the lung [3]
and brain [4], and oral mucositis due to antineoplastic therapy
wound healing, collagen production, and immune system
monochromaticity, the main property of laser light, that is,
an extremely narrow spectral area (line), which makes it much
easier to define and control the energy of the laser light, allo-
cate it on the surface, and deliver it to the required location [7].

The highly effective LLLT techniques are designed and
widely used: locally, in the projection of internal organs, laser
acupuncture, reflexology, intracavitary, and transdermal and
intravascular lighting, when called laser irradiation of blood
(ILIB), in addition to associated and combined techniques [8].
ILIB is a therapeutic technique that was first discovered and
performed in the former Soviet Union in the 1980s [9]. The
ILIB process modulates redox signaling in the respiratory
chain, through the stimulation of mitochondrial components,
being able to induce positive effects on the expression of im-
munoglobulins, interferons, and interleukins [10]. It is be-
lieved that this technique has several analgesic, spasmolytic,
and sedative effects [11]. It is also able to facilitate blood
circulation, causing widespread effects of intravenous blood
irradiation in almost all systems, and can be used in the treat-
ment of various diseases [12].
In addition, it increases the arteriovenous oxygen differ-
ence, which may be able to end tissue hypoxia and promote
oxygen enrichment, which is a sign of normalization of tissue
metabolism, and improves the oxidation of energy-carrying
molecules, such as glucose and pyruvate [13]. Besides the
elimination of hypoxia and the normalization of tissue metab-
olism, there is an increase in the synthesis of ATP with a
normalization of the cell membrane potential. Clinical and
laboratory studies have analyzed the therapeutic effects of
ILIB in many systemic conditions [6, 9, 10]. It has been re-
ported that more than 50 types of diseases can be treated with
this method, including cardiovascular and peripheral ischemic
vascular diseases (such as cerebral infarction, heart failure,
acute myocardial infarction, and angina pectoris); infectious,
autoimmune, and connective tissue diseases; nervous and
mental disorders; endocrine metabolic disease; acute chole-
cystitis; and acute and chronic diseases, such as bronchitis
and pneumonia [14].
Despite the biological effects, such as inflammation mod-
ulation and hemoglobin oxygenation, promoted by PBM [1],
there is still no consensus in the literature on the parameters to
be used in this form of treatment and on its effectiveness in
improving the clinical condition of patients who undergo
treatment with ILIB. Thus, the aim of the present study was
to carry out an integrative review of the literature on the ef-
fectiveness of ILIB as an adjuvant therapy in the treatment of
chronic systemic diseases.
Methods
The theme of this integrative literature review was established
based on the following clinical question: “Is ILIB an effective
adjunctive therapeutic alternative in the treatment of chronic
systemic diseases?” This study included non-randomized and
randomized controlled clinical trials that specifically evaluat-
ed the therapeutic effect of ILIB on chronic systemic diseases,
Lasers Med Sci
without restriction of time, and written in English. The exclu-
sion criteria were studies not related to the theme, review
articles, case reports, letters to the editor/editorials, personal
opinions, books/book chapters, textbooks, reports, conference
abstracts, patents, and laboratory studies.
The Medical Publications (PubMed)/MEDLINE database
(including electronic publications ahead of print) was used as
the primary study source. A manual search was also per-
formed through a systematized analysis of the references of
eligible articles. MeSH (Medical Subject Headings) was used
to select search keywords with the Boolean operators “AND”/
“OR”. The search strategy included the following keywords:
“low-level light therapy”, “laser therapy”, “lasers (and the
synonym “laser”)”, “humans”, “patients”, “disease”, “blood”,
“treatment outcome”, “arteries” ,“chronic disease” and
“veins”. The results obtained were exported to the EndNote
Web™ software (Thomson Reuters, Toronto, Canada), and
the duplicates were removed. The remaining results were
exported to Microsoft Word™ 2013 (Microsoft Ltd.,
Washington, USA), and the remaining duplicates were re-
moved manually. The search was carried out in June 2020,
and a total of 357,342 articles were found. After identification
in the database, the search filters were applied, and 328,948
studies were eliminated. Afterwards, 28,377 duplicate studies
that were not related to the theme were excluded. Then, 17
papers have been through analysis of the title and abstract,
leading to the exclusion of three articles, thus maintaining
14 articles for reading the full text. Subsequently, 13 articles
were selected for this review (Fig. 1).
Results and discussion
The publications selected, based on the methods described
above, to assess the effectiveness of ILIB as an adjuvant ther-
apy in the treatment of chronic systemic diseases are described
in Tables 1 and 2. Table 1 contains information regarding the
main objective of the study and demographic data of the pa-
tients, in addition to the present systemic disease.
There seems to be widespread effects of ILIB on almost all
organ systems, so that this therapy can be used to treat various
diseases [15, 24]. In the present review, coronary heart disease
was the most prevalent [16–20], followed by diabetes mellitus
[6, 13, 15]. Percutaneous coronary intervention is a procedure
commonly performed in the treatment of coronary artery dis-
ease [19, 20], which is based on the mechanical dilation of
atherosclerotic lesions [19]. However, restenosis remains a
considerable problem that affects the long-term efficiency of
this procedure [18, 20].
Restenosis after coronary interventions is believed to be the
result of endothelial rupture that leads to thrombus formation,
vascular remodeling, and migration and proliferation of
smooth muscle cells [17]. The main cause of restenosis within
Lasers Med Sci

Table 1 Information from articles regarding the main objective of the study, number of patients, age, sex, and diagnosis of the disease

Authors Objective Number of patients Age (years) Diagnosis

per group/sex

Kazemikhoo et al. [6] To evaluate the effects of ILIB on the expression of 13 _ Type 2 diabetes
arginase and epidermal growth factor receptor in mellitus
type 2 diabetic patients.
Chiran et al. [9] To assess the efficacy of synergic administration of 23 12.3 ± 2.9 Juvenile idiopathic
ILIB and etanercept in selected subtypes of arthritis
juvenile idiopathic arthritis.
Huang et al. [10] To investigate the clinical effects of intravascular 11/female, 25/male 28 to 65 anos Spinal cord injury
laser irradiation of blood therapy on oxidative
stress and mitochondrial dysfunction in subjects
with chronic spinal cord injury resulting from
trauma.
Kazemikhoo et al. [13] To evaluate the effects of ILIB on the metabolites 4/female, 5/male Mean: 60/female, Type 2 diabetes
of blood in diabetic type 2 patients using 61.14/male mellitus
metabolomics.
Kazemikhoo and To compare blue and red light effects on the blood 15/female, 9/male 63.7 Type 2 diabetes
Ansari [15] sugar level in diabetic type 2 patients. mellitus
de Scheerder et al. [16] To evaluate the feasibility and safety of ILIB as an 81 _ Heart diseases
adjunct to coronary stent implantation or to treat
in-stent restenosis in patients.
de Scheerder et al. [17] To evaluate the feasibility of intravascular low-power 68 Mean: 64.9 Heart diseases
red laser light therapy to reduce restenosis in patients
after coronary stenting of de novo lesions compared
with a historic group.
Derkacz et al. [18] To evaluate the influence of low-power 808-nm laser 101 _ Heart diseases
illumination of coronary vessels after percutaneous
angioplasty in preventing restenosis.
Derkacz et al. [19] To determine the effect of intravascular low-energy 26/female, 75/male 59.1 ± 10.5 Heart diseases
laser irradiation used during percutaneous coronary
intervention on the activity of inflammatory process
assessed by the serum levels of interleukins.
Derkacz et al. [20] To evaluate the effect of intravascular low-level laser 26/female, 75/male 59.1 ± 10.5 Heart diseases
therapy on selected growth factor levels in subjects
undergoing percutaneous coronary interventions.
Timofeyev et al. [21] To look into the functional activity of blood T- and 69/female, 6/male 20 to 74 Rheumatoid arthritis
B-lymphocytes of peripheral blood in rheumatoid
patients treated with ILIB.
Burduli and Gutnova [22] To study the effect of ILIB on plasma content of 69/female, 16/male 53.1 ± 5.2 Chronic pancreatitis
chronic pancreatitis in patients with chronic
pancreatitis.
Babaev et al. [23] To evaluate clinical and laboratory efficiency of ILIB 86 23 to 72 Liver disease
course for short periods of time at short-term exposure
to low-power laser radiation minimizing the potential
risk of hypocoagulation.

a stent is neointimal hyperplasia caused by the activation of
smooth muscle cells induced by vessel damage and by the
implantation of a foreign body. This process has histological
and pathophysiological similarities with the healing of
wounds in other tissues [17]. This causes a local inflammatory
response, mediated mainly by interleukins and the production
of vascular endothelial growth factor (VEGF), which, in turn,
promotes adventitial angiogenesis. The constitutive expres-
sion of VEGF is increased after vascular injury. FGF-2
(fibroblast growth factor-2) can stimulate endothelial cells to
produce VEGF, and overexpression of VEGF has been found
in endothelial cells after injury and interruption in the endo-
thelial cell monolayer [20].
Despite the immunomodulation effect promoted by ILIB,
in the study by Derkacz et al. [20], ILIB at the injury site
during coronary angioplasty did not influence insulin-like
growth factor-1 (IGF-1) and VEGF concentrations. On the
other hand, in the study by Derkacz et al. [19], it was observed
that ILIB during the percutaneous coronary intervention pro-
cedure results in a decrease in the levels of pro-inflammatory
interleukin (IL) 1β and IL 6, as well as in an increase in the
levels of anti-inflammatory IL 10.

Fig. 1 Flowchart of the selection
process for the articles included in
the integrative review
In diabetes mellitus, there is a low serum insulin to gluca-
gon rate and high levels of fatty acids. Gluconeogenesis in-
creases in livers and secretes large amounts of low-density
lipoproteins and accumulation of fatty acids. These fatty acids
are oxidized by the liver, which produces acetone,
acetoacetate, and beta-hydroxybutyrate [13]. There is a de-
crease in arginine and a dysregulation of endothelial cells, as
well as an increase in pro-inflammatory cytokine activity. In
the study by Kazemikhoo et al. [6], a significant decrease in
the expression of positive cells for arginase and epidermal
growth factor receptor (EGFR) was observed after ILIB ther-
apy (P < 0.01), which can reduce neuroinflammation and its
secondary damage. EGFR has important roles in regulating
cell activation, and decreasing its expression can decrease tis-
sue inflammation [6]. Arginine causes the release of several
hormones, such as insulin, glucagon, adrenal catecholamines,
prolactin, and growth hormone [24], and the regulation of
arginase expression consequently leads to greater expression
of arginine.
In this review, two studies with chronic rheumatological
diseases, these being rheumatoid arthritis [21] and subtypes
of juvenile idiopathic arthritis [9], were also selected. In the
study of Chiran et al. [9], increased efficacy in remission of
subtypes of juvenile idiopathic arthritis was observed when
ILIB applied synergistically with etanercept. This is a tumor
necrosis factor alpha (TNFα) fusion protein inhibitor. TNFα
is a powerful pro-inflammatory cytokine and has increased
Lasers Med Sci
titers, both in serum and in the synovial fluid of juvenile idi-
opathic arthritis patients. This cytokine has two distinct sig-
naling pathways, mediated by two types of receptors, tumor
necrosis factor receptor 1 (TNFR1) and tumor necrosis factor
receptor 2 (TNRF2). Etanercept acts both as an antagonist, by
blocking the membrane-attached form of TNFα interaction
with TNFR1 or TNFR2, and as an agonist, by initiating re-
verse signaling [9].
Originally, in this treatment, the laser light directly irradi-
ates the circulating blood through a sterile disposable catheter,
introducing 2 mm of optical fiber [6]. In the studies selected in
this review, several vessels were used for the application of
ILIB, such as coronary artery [16–20], according to the pres-
ent disease. The most used wavelengths at ILIB include 630,
650, 890, and, more recently, 450 nm, which basically gener-
ate two possible types of action, the vascular endothelium and
the blood [25]. In the studies used for this review, two articles
used the blue light source, at a 405-nm wavelength [13, 15],
while the majority used red in the electromagnetic spectrum,
varying from 630 to 650 nm and the infrared at a 808-nm
wavelength. Only one study compared ILIB in two wave-
lengths, 630 nm and 808 nm; however, it was observed that
ILIB promoted similar and beneficial results in both blue and
red [15], while in one study, three light sources were used
synergistically, 405, 536, and red 630 nm [9].
Despite the varied parameters and protocols for using this
kind of therapy, all studies showed satisfactory results in the
Lasers Med Sci

Table 2 ILIB usage protocols and main results found in the selected studies

Authors Methods Laser parameters Location of the Application time Main results
application

Kazemikhoo Samples of venous blood Wavelength: 630 nm. Cubital vein 1800 s Laser therapy can have a
et al. [6] without fasting were Power density: beneficial effect for
collected in standard 1.5 mW/cm2 diabetic patients by
5-ml sodium heparin decreasing the
tubes for flow cytome- expression of arginase
try for study before and and activating the nitric
after laser therapy. oxide synthase/nitric
oxide pathway, in-
creasing nitric oxide
production and
vasodilation, and de-
creasing the expression
of EGFR which can
reduce neuroinflamma-
tion.
Chiran et al. The patients were Wavelength: 630 nm at Cubital region, but if no Laser therapy was given ILIB and etanercept have
[9] randomized into two the beginning of the vein could be located, in three sets (10 min an increased efficacy in
asymmetric groups, session, followed by alternate sites at the for each wavelength) promoting the
using block green radiation forearm or the dorsal of five consecutive remission of selected
randomization with an (536 nm) and violet region of the hand were daily sessions, with a subtypes of juvenile
allocation ratio of 3:2. radiation (405 nm) at used. Large veins at 7-week interval be- idiopathic arthritis, if
Group I (60% of the the end. palpation were the tween every set of applied synergistically.
patients) received ILIB, standard of choice. sessions.
and group II (40% of the
patients) received
placebo laser. This was
also combined with
stratified randomization
to ensure a good balance
of arthritis subtypes in
each group.
Huang et al. The study group Wavelength: 632.8 nm. A 24-gage intravenous 3600 s: 15 times in ILIB intervention
[10] underwent 1 h daily of Energy: 14.4 J. catheter was used for 3 weeks significantly increase
ILIB for 15 days over Power: 4 mW an elbow venous punc- subjects’ mitochondrial
3 weeks. The sham ture (phlebotomy). DNA copy number,
group underwent ILIB white blood cell
with no laser power. adenosine triphosphate
synthesis, and total
antioxidant capacity;
significantly reduce
malondialdehyde
production;
significantly decrease
LDL; and significantly
increase HDL.
Kazemikhoo Were compared blood Wavelength: 405 nm. Large veins of the upper 1800 s The results showed
et al. [13] samples of nine diabetic Power: 1.5 mW limb significant decrease in
type 2 patients, using glucose, glucose 6
metabolomics, before phosphate,
and after ILIB with a dehydroascorbic acid,
blue-light laser. R-3 hydroxybutyric
acid, L-histidine, and
L-alanine, and signifi-
cant increase in
L-arginine level in
blood, and blood sugar
levels in the patients
have reduced signifi-
cantly (p < 0.05)
A vein in the forearm.
 Lasers Med Sci

Table 2 (continued)

Authors Methods Laser parameters Location of the Application time Main results
application

Kazemikhoo Each blue and red laser Red laser (630 nm) and 25,200 s: 1800 s per No significant differences
and Ansari therapy was prescribed blue (405 nm). session, making a total were found between
[15] at least seven times for Power density: of 14 sessions. wavelengths, but the
each patient, and the 1.5 mW/cm2 highly significant
blood sugar level of all effect of ILIB, using
patients was measured each of these
before and after laser wavelengths, on
therapy with the decreasing blood sugar
ExiChek blood glucose levels suggests this as
monitoring system. an effective therapeutic
method in type 2
diabetic patients. ILIB
can be an effective
therapy in diabetic
patients, alone or
associated with
medications.
de Scheerder Eighty-one patients were Wavelength: 650 nm. Coronary artery 60 s ILIB can easily be used as
et al. [16] treated with ILIB, for Power: 30 mW. an adjunct to stent
in-stent restenosis Power: 1.8 J. Energy deployment or as a new
(n = 27), elective density: 0.95 J/cm2 treatment modality for
stenting for recurrent in-stent restenosis. No
restenosis (n = 16), and procedural or
stenting for treatment of in-hospital complica-
a suboptimal percutane- tions occurred in con-
ous transluminal coro- junction of the use of
nary angioplasty result ILIB.
(n = 38).
De Scheerder Sixty-eight consecutive Wavelength: 650 nm. Coronary artery 180 s Angiographic follow-up
et al. [17] patients with angina Energy: 1.8 J. revealed restenosis in
class 2 to 4 with at least Power: 10 mW nine patients (14.7%).
one high-grade stenosis Red-light intravascular
were used consecutive- therapy is safe, is
ly. feasible, and has re-
duced the rate of reste-
nosis after coronary
stenting.
Derkacz The procedure of laser Wavelength: 808 nm. Coronary artery _ Intravascular laser
et al. [18] intravascular Energy density: illumination can bring
illumination was 9 J/cm2. Power advantages comparable
performed on 52 density: to those of drug-eluting
patients (laser group), 100 mW/cm2 stents without risk of
and another 49 patients late thrombosis.
formed the control
group. All patients were
monitored for major
adverse cardiac events
at the 6- and 12-month
follow-up points.
Derkacz In 52 subjects, additional Wavelength: 808 nm. Coronary arteries _ In patients undergoing
et al. [19] radiation of the dilatated Energy density: laser angiography,
lesion was performed 9 J/cm2. Power restenosis was
(laser group). The density: observed in six cases
remaining 49 subjects 100 mW/cm2 (15%), and in the
underwent a classical control group, it
angioplasty procedure appeared in 12 cases
and constitute the (32.4%). A
control group. After the significantly lower
procedure, all patients mean stenosis was
were given observed in the
Lasers Med Sci

Table 2 (continued)

Authors Methods Laser parameters Location of the Application time Main results
application

acetylsalicylic acid, laser-treated group,

clopidogrel, which resulted in a
simvastatin, and, when lower degree of steno-
possible, the sis in patients diag-
angiotensin-converting nosed with restenosis.
enzyme inhibitor and
β-adrenolytic agent.
Derkacz In all individuals, serum Wavelength: 808 nm. Coronary artery 90 s In irradiated individuals, a
et al. [20] levels of insulin-like Energy density: control angiography
growth factor-1 9 J/cm2. Power revealed a lower rate of
(IGF-1), vascular endo- density: late weight loss when
thelial growth factor 100 mW/cm2 compared with the
(VEGF), transforming control group.
growth factor-b1
(TGF-b1), and fibro-
blast growth factor-2
(FGF-2) were measured
before angioplasty, then
6 and 12 h and 1 month
after the procedure. In
all patients, a control
angiography was per-
formed 6 months later.
Timofeyev The immunological study Wavelength: 632.8 nm. Cubital vein Three to five sessions, ILIB provided some
et al. [21] of peripheral blood of Power density: with a week interval symptomatic but
patients was conducted 1.0 ± 0.1 mW/cm2 between each session. unstable relief in
before and after each The duration of one patients with a high
ILIB procedure. The session was 1200 s level of circulating
blood level of immune complexes
circulating immune and a high functional
complexes was activity of
observed. The T-lymphocytes. There
functional properties of was no effect in
T- and B-lymphocytes patients with a high
were investigated in the level of circulating
rosette-forming test and immune complexes
leucocyte migration and decreased number
test. The ability of Th of lymphocytes.
and Ts to form stable
rosettes in the
theophylline-sensitive
test was also studied.
Burduli and The control group Wavelength: 630 nm. _ Seven daily irradiation After addition of ILIB to
Gutnova comprised 45 patients Power: 1.5–2.0 mW sessions (each session: complex therapy of
[22] receiving drug therapy 1200 s) exacerbation of chronic
including analgesics, pancreatitis, the
spasmolytics, protease initially elevated
inhibitors, antisecretory concentration of
drugs, infusion therapy, ceruloplasmin in blood
and enzymes. Patients plasma significantly
of the main group decreased and returned
(n = 45) apart from the to normal.
same drug therapy
additionally received
ILIB
Babaev et al. The main group included Power: 2 mW Cubital vein 900 s a day for 7 days Traditional therapy
[23] patients with chronic supplemented for
nonspecific liver 7 days in the
diseases with signs of low-intensity ILIB
the hepatocellular course was followed by
insufficiency syndrome, a significant, more
 Lasers Med Sci

Table 2 (continued)

Authors Methods Laser parameters Location of the Application time Main results
application

who received a course pronounced reduction

of ILIB during the in total bilirubin, trans-
treatment additionally to aminase activity, LDH
the basic therapy. and AP levels, and in-
The control group creased total cholester-
included patients treated ol.
for chronic
parenchymal liver
disease with clinical
features of
hepatocellular
insufficiency. They
received no ILIB course
along with basic
therapy.

clinical condition of patients, regardless of the disease in ques-
tion. However, studies on the effect of this therapy on various
diseases are still scarce in the literature, and there is a need for
more well-designed clinical trials to better understand the role
of ILIB in various systemic diseases. One of the limitations of
this review was the restriction of the database to only one,
despite being considered the most used by the scientific com-
munity and where most important international journals are
indexed.
Conclusion
The present review allowed the identification of the main clin-
ical studies about ILIB found in the English literature, thus
allowing the confirmation of their positive participation in the
various chronic systemic diseases, with respect to the modu-
lation of inflammation, decreasing the levels of pro-
inflammatory cytokines. On the other hand, it was possible
to observe a variety of protocols for the use of this therapy,
confirming once again the need for more clinical trials that
establish standardized protocols. In addition, it is also neces-
sary to elucidate knowledge in relation to its disadvantages
and contraindications, a point not addressed by the studies.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical approval This article does not contain any studies with human
participants or animals performed by any of the authors.
Informed consent The patients provided informed consent.
References
1. Wang X, Tian F, Soni SS, Gonzalez-Lima F, Liu H (2016)
Interplay between up-regulation of cytochrome-c-oxidase and he-
moglobin oxygenation induced by near-infrared laser. Sci Rep 6:
30540. https://doi.org/10.1038/srep30540
2. Hamblin MR (2017) Mechanisms and applications of the anti-
inflammatory effects of photobiomodulation. AIMS Biophys 4(3):
337–361. https://doi.org/10.3934/biophy.2017.3.337
3. Miranda da Silva C, Peres Leal M, Brochetti RA, Braga T, Vitoretti
LB, Câmara NOS et al (2015) Low level laser therapy reduces the
development of lung inflammation induced by formaldehyde expo-
sure. PLoS One 10(11):e0142816. https://doi.org/10.1371/journal.
pone.0142816
4. Wang X, Tian F, Reddy DD, Nalawade SS, Barrett DW, Gonzalez-
Lima F, Liu H (2017) Up-regulation of cerebral cytochrome-c-
oxidase and hemodynamics by transcranial infrared laser stimula-
tion: a broadband near-infrared spectroscopy study. J Cereb Blood
Flow Metab 37(12):3789–3802. https://doi.org/10.1177/
0271678X17691783
5. Cavalcanti AL, de Macêdo DJ, Dantas FSB, Menezes KS, Silva
DFB, de Melo Junior WA, Cavalcanti AFC (2018) Evaluation of
oral mucositis occurrence in oncologic patients under antineoplastic
therapy submitted to the low-level laser coadjuvant therapy. J Clin
Med 7(5):90. https://doi.org/10.3390/jcm7050090
6. Kazemikhoo N, Sarafnejad AF, Ansari F, Mehdipour P (2016)
Modifying effect of intravenous laser therapy on the protein expres-
sion of arginase and epidermal growth factor receptor in type 2
diabetic patients. Lasers Med Sci 31(8):1537–1545. https://doi.
org/10.1007/s10103-016-2012-x
7. de Freitas LF, Hamblin MR (2016) Proposed mechanisms of
photobiomodulation or low-level light therapy. IEEE J Sel Top
Quantum Electron 22(3):7000417. https://doi.org/10.1109/
JSTQE.2016.2561201
Lasers Med Sci
8. Moskvin SV (2017) Low-level laser therapy in Russia: history,
science and practice. J Lasers Med Sci 8(2):56–65. https://doi.org/
10.15171/jlms.2017.11
9. Chiran DA, Litscher G, Weber M, Ailioaie LM, Ailioaie C,
Litscher D (2013) Intravenous laser blood irradiation increases ef-
ficacy of etanercept in selected subtypes of juvenile idiopathic ar-
thritis: an innovative clinical research approach. Evid Based
Complement Alternat Med 2013:168134. https://doi.org/10.1155/
2013/168134
10. Huang SF, Tsai YA, Wu SB, Wei YH, Tsai PY, Chuang TY (2012)
Effects of intravascular laser irradiation of blood in mitochondria
dysfunction and oxidative stress in adults with chronic spinal cord
injury. Photomed Laser Surg 30(10):579–586. https://doi.org/10.
1089/pho.2012.3228
11. Momenzadeh S, Abbasi M, Ebadifar A, Aryani M, Bayrami J,
Nematollahi F (2015) The intravenous laser blood irradiation in
chronic pain and fibromyalgia. J Lasers Med Sci 6(1):6–9
12. Yang WH, Lin SP, Chang ST (2017) Case report: rapid improve-
ment of crossed cerebellar diaschisis after intravascular laser irradi-
ation of blood in a case of stroke. Medicine (Baltimore) 96(2):
e5646. https://doi.org/10.1097/MD.0000000000005646
13. Kazemi Khoo N, Iravani A, Arjmand M, Vahabi F, Lajevardi M,
Akrami SM, Zamani Z (2013) A metabolomic study on the effect of
intravascular laser blood irradiation on type 2 diabetic patients.
Lasers Med Sci 28(6):1527–1532. https://doi.org/10.1007/s10103-
012-1247-4
14. Xu Y, Lin Y, Gao S (2015) Study on the selection of laser wave-
lengths in the intravascular low-level laser irradiation therapy.
Lasers Med Sci 30(4):1373–1376. https://doi.org/10.1007/s10103-
015-1732-7
15. KazemiKhoo N, Ansari F (2015) Blue or red: which intravascular
laser light has more effects in diabetic patients? Lasers Med Sci
30(1):363–366. https://doi.org/10.1007/s10103-014-1672-7
16. de Scheerder IK, Wang K, Zhou XR, Szilard M, Verbeken E, Ping
QB, Yanming H, Jianhu H, Van de Warf F (2000) Intravascular
low-power red laser light as an adjunct to coronary stent implanta-
tion: initial clinical experience. Catheter Cardiovasc Interv 49(4):
468–471. https://doi.org/10.1002/(sici)1522-726x(200004)49:
4<468::aid-ccd27>3.0.co;2-y
17. de Scheerder IK, Wang K, Kaul U, Singh B, Sahota H, Keelan MH,
Kipshidze NN, Moses J (2001) Intravascular low-power laser irra-
diation after coronary stenting: long-term follow-up. Lasers Surg
Med 28(3):212–215. https://doi.org/10.1002/lsm.1040
18. Derkacz A, Protasiewicz M, Poreba R, Szuba A, Andrzejak R
(2010) Usefulness of intravascular low-power laser illumination
in preventing restenosis after percutaneous coronary intervention.
Am J Cardiol 106(8):1113–1117. https://doi.org/10.1016/j.
amjcard.2010.06.017
19. Derkacz A, Protasiewicz M, Poręba R, Doroszko A, Andrzejak R
(2013) Effect of the intravascular low energy laser illumination
during percutaneous coronary intervention on the inflammatory
process in vascular wall. Lasers Med Sci 28(3):763–768. https://
doi.org/10.1007/s10103-012-1142-z
20. Derkacz A, Protasiewicz M, Rola P, Podgorska K, Szymczyszyn A,
Gutherc R, Poręba R, Doroszko A (2014) Effects of intravascular
low-level laser therapy during coronary intervention on selected
growth factors levels. Photomed Laser Surg 32(10):582–587.
https://doi.org/10.1089/pho.2013.3700
21. Timofeyev VT, Poryadin GV, Goloviznin MV (2001) Laser irradi-
ation as a potential pathogenetic method for immunocorrection in
rheumatoid arthritis. Pathophysiology 8(1):35–40. https://doi.org/
10.1016/s0928-4680(00)00059-6
22. Burduli NM, Gutnova SK (2010) Effect of intravenous laser irradi-
ation of the blood on plasma content of ceruloplasmin in patients
with chronic pancreatitis. Bull Exp Biol Med 149(6):697–698.
https://doi.org/10.1007/s10517-010-1027-8
23. Babaev AV, Gogolev DE, Reiner OV, Korochkin IM, Fandeev
AV, Pivovarov VY, Fedulaev YN, Drachan KM (2012) Effect of
intravenous low-intensity laser irradiation of the blood on clinical
and laboratory parameters of hepatocellular insufficiency. Bull Exp
Biol Med 153(5):754–757. https://doi.org/10.1007/s10517-012-
1818-1
24. Kazemikhoo N, Ansari F, Nilforoushzadeh (2015) The hypoglyce-
mic effect of intravenous laser therapy in diabetic mellitus type 2
patients; a systematic review and meta-analyses. Med Clin Rev 1:7.
https://doi.org/10.21767/2471-299X.1000007
25. Mi XQ, Chen JY, Liang ZJ, Zhou LW (2004) In vitro effects of
helium-neon laser irradiation on human blood: blood viscosity and
deformability of erythrocytes. Photomed Laser Surg 22(6):477–
482. https://doi.org/10.1089/pho.2004.22.477
Publisher’s note Springer Nature remains neutral with regard to jurisdic-
tional claims in published maps and institutional affiliations.