Stanford University School of Medicine, CA, USA
Low Level Light Therapy, or LLLT, is a very important new area of photomedicine. However, there
are a number of reasons why LLLT has not been accepted into the main stream of science and
medicine, and I will discuss a few of them below. Let me add, however, that I know from personal
experience that LLLT works on wound healing, and carpal tunnel syndrome, when done properly.
I have been trying for over 40 years to teach photobiology to laser people, and more recently, to
LED people as well. At a laser meeting in the 1970s, at the height of the feeling that lasers were
magical, I made a slide to demonstrate the biological effect of a laser. It showed a man dropping a
big laser on his foot, and yelling OUCH. I said that this is the ONLY type of biological effect that a
laser can have on a person. A laser is an expensive flashlight, and it is the light produced BY the
laser that has a chance of producing a biological effect, assuming that it is of the correct wavelength and output, etc.
Because so many bad papers have been published on LLLT, it has not achieved the universal
acceptance that that it deserves. There are two main reasons for bad papers on LLLT; one is the
lack of proper scientific training by the authors, and the other is their lack of knowledge of photobiology. I will give you some examples of very bad science.
At an LLLT Congress some years ago, the speaker proclaimed that LLLT was effective at reducing high blood
pressure. In the so-called clinical trial, the patient came
in and had his blood pressure taken. Then various
areas around the patient's neck were irradiated with a
laser, whose wavelength I don't remember. Then they
measured the patient's blood pressure again, and low
and behold, the blood pressure was lower. Was this
another magical success for LLLT? NO!
I asked the speaker if he had also tested the patient's
blood pressure 30 minutes after the therapy, or after 1
hour, or 2 hours, and he said no. Then I told him my
story. While preparing for my trip to that Congress, I
was running about the drug store picking up toothpaste, etc., and I saw a new blood pressure machine,
and decided to try it. My blood pressure was way
above normal. After a few moments of sitting and
reading the signs on the machine, I decided to test my
blood pressure again, and low and behold it was normal, even without laser treatment. Sitting down in a
chair for a few moments worked magic.
energy densities for the 904 nm LED was much lower
(25.5 and 16.9 J/cm2) than those of the 633 nm laser
(132.7 and 39.8 J/cm2). Could this be the reason for
the failure of the 904 nm radiation?
Also, the light treatment only delayed the death of the
nerve, it did not reverse the damage. So what is the
point of the publication? It is not a success story for
LLLT. It is bad science. This paper should not have
been published.
Unfortunately, this paper is cited in “The Laser Therapy
Handbook” 2; p.13) as proving that coherence is very
important in LLLT.
Enwemeka et al. 3,4) have published two papers about
controlling infections of methicillin-resistant
Staphylococcus aureus with blue light. This is certainly
of great interest, but in each paper these authors proclaim with wonderment that the survival curves are not
linear.
decades. Of course, radiation survival curves are NOT
linear, and no radiation biologist would plot data on
linear graph paper. They use semi-log plots, because
these plots provide a lot of information about the
organism being studied.
Figure 1 shows a survival curve on Staphylococcus
aureus, which was irradiated with blue light, and plotted with linear coordinates. 4) All that one can conclude from this plot is that cells were killed.
However, if you plot the same data on semi-log paper,
you obtain much more useful information (Figure 2).
You immediately see that 30% of the cells are much
more sensitive than the remaining 70%, and both
curves show one-hit kinetics. But why are there two
populations of cells with markedly different sensitivities to blue light?
Since the authors do not mention how the bacteria
were grown, we do not know if part of the cells were
in a different phase of the cell cycle, e.g., stationary
phase, and this might be why their radiation sensitivity
was different. Without a proper description of how the
authors performed this experiment, we will never
know the answer.
from these survival curves; the slope of the lines (D0),
where extensions of the curve crosses the 100% sur-
vival line (Dq), or crosses the zero dose line (n), etc.
So the conclusion is, if you are going to run radiation
biology experiments, you should first learn how to
perform radiation biology experiments, and how to
plot, and interpret the data.
Clearly, the absence of proper scientific training is a
big factor in the production of bad papers on LLLT. I
don't want to put ALL of the blame on authors for bad
papers, I also have to include bad reviewers and bad
editors, and, unfortunately, there are a lot of these.
Fortunately, there are only a few basic laws of photobiology, but if researchers and clinicians do not know
them, then their studies will be worthless, and they
will mislead other people who are similarly untrained.
Again, I have to put some of the blame on bad reviewers and bad editors.
The First Law of Photochemistry states that: light
must be absorbed for photochemistry to occur. This is
a very simple concept, but it is the basis for performing photobiological experiments correctly.
Since photobiological and phototherapeutic effects are
initiated by photochemistry, unless light of a particular
wavelength is absorbed by a system, no photochemistry will occur, and no photobiological effects will be
observed, no matter how long one irradiates with that
wavelength of light. A significant number of papers in
the laser and LED phototherapy literature would not
have been published if the authors and the reviewers
had known the First Law of Photochemistry.
And now for a word of caution. You should not
believe everything that you read. Just because it is
published in a book, this does not make it true.
Many of you know that I started the American Society
for Photobiology, but I bet that none of you know that
I am also considered to be the Father of Photochemistry.
It must be true, it is in the book by Tuner and Hode! 2;
p.336)
“According to what is known as ‘Kendrick Smith's First
Law of Photo Chemistry', light must be absorbed
before photochemistry can occur.”
Figure 3. Ultraviolet radiation survival curve for
different strains of Escherichia coli.
Not only do they have it wrong about the First Law of
Photochemistry, they also spelled my first name incorrectly. There is no “ K” at the end of Kendric.
Unfortunately, there are a great number of errors in
this book.
The First Law of Photochemistry has been around
since the 1800's. Actually, it is known as the GrotthusDraper Law.
Low Level Light Therapy is real and beneficial, and I
get very upset when people publish false statements,
or perform bad science and photobiology. Until the
LLLT field gets rid of the bad science and falsehoods
that are published, LLLT will continue to be considered
snake oil medicine by most qualified scientists and
physicians.
There are two other laws of photochemistry that
should be mentioned for the sake of completeness,
even though they have little relevance to phototherapy.
The Second Law of Photochemistry states that for
each photon of light absorbed by a chemical system,
only one molecule is activated for a photochemical
reaction.
This law is true for ordinary light intensities, however,
with high-powered lasers, two-photon reactions can
occur. Two-photon reactions are not important for
LLLT.
er the dose.
This law is true for chemicals in a test tube, but the
response of cells to radiation usually involves a
sequence of interacting biological reactions, making a
linear “dose x time” relationship highly unlikely. For
example, giving a total UV radiation dose to cells all at
once kills more cells than the same dose when fractionated. DNA repair systems are induced by the first
irradiation, and have a chance to repair much of the
damage before the next irradiation.
There is no reciprocity when damage is produced
and repaired, but there is reciprocity over a narrow
range of doses for photoreceptors that trigger a
response, such as phytochrome in plants. The relevancy of reciprocity to LLLT remains to be demonstrated.
An Absorption Spectrum is a plot of the probability
that light of a given wavelength will be absorbed by
the system under investigation. Because of its unique
electronic structure, each chemical compound has a
different absorption spectrum.
The Bunsen-Roscoe Law of Reciprocity: a photochemical effect is directly proportional to the total
energy dose, irrespective of the time required to deliv-
Each of the wavelengths absorbed by a chemical compound will be absorbed to different degrees, again
because of the unique electronic structure of the compound. Therefore, an absorption spectrum of the compound that one is interested in will determine the optimum wavelength to use to obtain the maximum
absorption with the least amount of light (Figure 4).
into tissues might produce the best effect in deep tissues, even though that wavelength was not the most
efficient in a thin layer of cells.
To quote from a review by Calderhead: 8) “To sum up,
the wavelength of a therapeutic source therefore has a
double importance, namely to ensure absorption of the
incident photons in the target chromophores, and to
be able to do so at the depths at which these chromophores exist. The waveband in which the wavelength of the incident photons is located determines
not only which part of the cell is the target, but also
the primary photoaction. Wavelength is thus probably
the single most important consideration in phototherapy, because without absorption, there can be no reaction.”
Another point discussed in this review is that two different wavelengths might produce a better effect under
certain conditions, such as wound healing. Calderhead
8) reports that mast cells, neutrophils, and
macrophages are the first cells to respond to a wound,
and that these cells respond best to 830 nm light. In
contrast, fibroblasts, which are involved later, respond
better to 633 nm light. The suggestion has been made
that it might be better to irradiate first with 830 nm
light, followed by 633 nm light, and then again with
833 nm light to activate the myofibroblasts.
The multiplicity of cell types in tissues, and the concept that they may respond better to different wavelengths, does complicate the phototherapy of tissues. It
is just one more thing to keep in mind when planning
experiments or clinical trials.
A requirement for a good paper on photobiology is to
specify everything about the light source, i.e., wavelength(s), power, dose, area of exposure, time, etc.,
There are published experimental and clinical studies
that were conducted with good scientific methodology,
but they did not describe the characteristics of the light
source, or they did not even mention the light source.
Therefore, these studies cannot be repeated or extended by another author. Such a paper is totally useless.
This is like describing a new cure for cancer, without
mentioning the name of the drug that was used in the
clinical study.
So many acronyms are used in the Low Level Laser
Therapy field that it is confusing to readers, e.g., low
level laser therapy (LLLT), low-power laser irradiation
(LPLI), low power laser therapy (LPLT), low-energy
laser irradiation (LELI), etc., etc. It would be a great
boon to the field if there could be some standardization of nomenclature. Since lasers just produce light, I
would urge the use of the simple and preferred term,
PHOTOTHERAPY.
The wavelength of light produced by the laser must be
specified, preferably throughout the text of an article in
place of acronyms like He-Ne laser.
Also, a laser should be chosen for the wavelength of
light that it produces, not because, and I quote from a
published paper, “The selection of such a laser for
therapeutic use was based on its safety and commercial availability.” Whatever happened to WAVELENGTH? This is another example of bad science and
bad reviewers.
Even with the proper wavelength and dose of radiation, phototherapy will not be effective on every system and/or situation. The magnitude of the phototherapy effect depends on the physiological state of the
cells at the moment of irradiation. For example, when
irradiating fresh wounds, the effect of the irradiation
can be minimal or nonexistent. This happens when
cellular proliferation is active, and the regeneration of
the tissue is occurring at a more or less normal rate.
Light will only stimulate cell proliferation if the cells
are growing poorly at the time of the irradiation. If a
cell is fully functional, there is nothing for radiation to
stimulate, and no therapeutic benefit will be observed.
An analogy would be that patients will show NO beneficial effect of vitamin therapy if they already receive
an adequate supply of vitamins in their daily diet.
It should be cautioned, however, that an excessive
dose of radiation can be detrimental. Thus, at proper
doses of light there can be a stimulation of growth, but
at high doses an excessive amount of singlet oxygen
may be produced, and its chemical action can be detrimental to cells. This is another reason for determining
an action spectrum.
More and more papers are appearing in the light therapy literature using non-laser light sources, such as
LEDs. As with laser studies, all the characteristics of the
light emitted by the light source must be specified if a
paper is to be useful.
Phototherapy, whether using low intensity radiation of
the proper wavelength from a laser, an LED, or a filtered incandescent lamp, can be beneficial in a number of clinical situations, from pain remission to wound
healing. Unfortunately, the absence of this type of phototherapy from the mainstream of medicine makes it
currently unavailable to many patients who would
benefit from it.
The absence of this type of therapy from the mainstream of science and medicine is because so many of
the studies have been conducted without proper scientific methodology, and performed by people who lack
an understanding of the properties and biological
effects of light.
This paper is a plea to scientists, physicians, phototherapy groups, societies and journals, to raise the standards for running and publishing experiments and clinical trials, by learning the basics of photobiology, and
thereby accelerating the acceptance of Low Level Light
Therapy into the mainstream of science and medicine.
Great progress has been made in the last 10 years, but
we still have a way to go.