Photobiomodulation

Harvest with her copy of Intermediate Physics for Medicine and Biology.

My Treeing Walker Coonhound Harvest is getting older and having some trouble with arthritis. The vet says she’s showing signs of hip dysplasia, but it’s not too severe yet. I want to nip this problem in the bud, so we have started a treatment regime that includes oral supplements, pain medication, moderate exercise, weight control, and massage. We’re also trying photobiomodulation, sometimes called low-level laser therapy or cold laser therapy.

Russ Hobbie and I don’t mention photobiomodulation in Intermediate Physics for Medicine and Biology. Is it for real? That’s what I want to discuss in today’s blog post. I’ll give you a hint: my answer will be “maybe.”

Harvest getting photobiomodulation treatment.

We bought a device called Lumasoothe 2 Light Therapy for Pets (lumasoothe.com). I use it in it’s IR Deep Treatment Mode, which shines three wavelengths of light—infrared (940 nm), red (650 nm) and green (520 nm)—from an array of light emitting diodes. I doubt the green light can penetrate to the hip, but red and especially infrared are not attenuated as much. In IPMB, Russ and I talk about how red light is highly scattered, and you can see that by noticing how the red spreads out to the sides of the applicator (kind of like when you hold a flashlight up to your mouth and your checks glow red). The light is delivered in pulses that come at a frequency of about 2.5 Hz (I used the metronome that sits atop my piano to estimate the frequency). I can’t imagine any advantage to pulsing the light, and suspect it’s done simply for the visual effect. I apply the light to Harvest’s hips, about 15 minutes each side.

Mechanisms and Applications of the Anti-Inflammatory Effects of Photobiomodulation.

When we first purchased the device, I assumed it worked by heating tissue. But researchers and device manufacturers insist the mechanism is not thermal. So how does it work? To explore that and other issues, I searched the literature, and found a particularly clear open-access review article by Michael Hamblin, then with the Harvard-MIT Division of Health Sciences and Technology: “Mechanisms and applications of the anti-inflammatory effects of photobiomodulation” (AIMS Biophysics, Volume 4, Pages 337–36, 2017). Hamblin has a long history of research on photodynamic therapy (analyzed in Chapter 14 of IPMB), and his more recent work has focused on photobiomodulation.

Hamblin begins (with references removed),

Photobiomodulation (PBM) was discovered almost 50 years ago by Endre Mester in Hungary. For most of this time PBM was known as “low-level laser therapy” as ruby laser (694 nm) and HeNe lasers (633 nm) were the first devices used. Recently a consensus decision was taken to use the terminology “PBM” since the term “low-level” was very subjective, and it is now known that actual lasers are not required, as non-coherent light-emitting diodes (LEDs) work equally well. For much of this time the mechanism of action of PBM was unclear, but in recent years much progress has been made in elucidating chromophores and signaling pathways.

Any time you are talking about a therapy, the dose is crucial. According to a study by medcovet, the output of Lumasoothe is 0.225 J/cm² per minute (it’s advertised at 6.4). I don’t know which of these values to use, so I’ll just pick something in the middle: 1 J/cm². If we divide by 60 seconds, this converts to about 0.017 W/cm². The intensity of sunlight that reaches the earth’s surface is about 0.1 W/cm², so the device puts out less than the intensity of sunlight (at noon, at the equator, with no clouds). The advertised intensity would be similar to the intensity of sunlight. Of course, sunlight includes a wide band of frequencies, while the Lumasoothe emits just three. 

There seems to be an optimum dose, as is often found in toxicology. Hamblin explains

The “biphasic dose response” describes a situation in which there is an optimum value of the “dose” of PBM most often defined by the energy density (J/cm²). It has been consistently found that when the dose of PBM is increased a maximum response is reached at some value, and if the dose in increased beyond that maximal value, the response diminishes, disappears and it is even possible that negative or inhibitory effects are produced at very high fluences.

Joules per square centimeter per minute may not be the best unit to assess heating effects of the Lumasoothe. Let’s assume that 0.017 W/cm² of light penetrates into the tissue about one centimeter (a guess). This means that the device dumps 0.017 watts into a cubic centimeter of tissue. That volume of tissue has a density of about that of water: 1 g/cm³. So the specific absorption rate should be about 0.017 W/g or 17 W/kg. That’s not negligible. A person’s metabolism generates only about 1.5 W/kg. Diathermy to heat tissues uses about 20 W/kg. I don’t think we can rule out some heating using this device. (However, I shined it on my forearm for about two minutes and didn’t feel any obvious warming.)

Hamblin believes there are non-thermal mechanisms involved.

Cytochrome c oxidase (CCO) is unit IV in the mitochondrial electron transport chain. It transfers one electron (from each of four cytochrome c molecules), to a single oxygen molecule, producing two molecules of water. At the same time the four protons required, are translocated across the mitochondrial membrane, producing a proton gradient that the ATP synthase enzyme needs to synthesize ATP. CCO has two heme centers (a and a3) and two copper centers (CuA and CuB). Each of these metal centers can exist in an oxidized or a reduced state, and these have different absorption spectra, meaning CCO can absorb light well into the NIR [near infrared] region (up to 950 nm). Tiina Karu from Russia was the first to suggest that the action spectrum of PBM effects matched the absorption spectrum of CCO, and this observation was confirmed by Wong-Riley et al in Wisconsin. The assumption that CCO is a main target of PBM also explains the wide use of red/NIR wavelengths as these longer wavelengths have much better tissue penetration than say blue or green light which are better absorbed by hemoglobin. The most popular theory to explain exactly why photon absorption by CCO could led [sic] to increase of the enzyme activity, increased oxygen consumption, and increased ATP production is based on photodissociation of inhibitory nitric oxide (NO). Since NO is non-covalently bound to the heme and Cu centers and competitively blocks oxygen at a ratio of 1:10, a relatively low energy photon can kick out the NO and allow a lot of respiration to take place.

That’s a considerable amount of biochemistry, which I’m not an expert in. I’ll assume Hamblin knows a lot more about it than I do. I worry, however, when he writes “the assumption that…” and “the most popular theory…” It makes me wonder how well this mechanism is established. He goes on to suggest other mechanisms, such as the production of reactive oxygen species and a reduction in inflammation.

Hamblin concludes

The clinical applications of PBM have been increasing apace in recent years. The recent adoption of inexpensive large area LED arrays, that have replaced costly, small area laser beams with a risk of eye damage, has accelerated this increase in popularity. Advances in understanding of PBM mechanisms of action at a molecular and cellular level, have provided a scientific rationale for its use for multiple diseases. Many patients have become disillusioned with traditional pharmaceutical approaches to a range of chronic conditions, with their accompanying distressing side-effects and have turned to complementary and alternative medicine for more natural remedies. PBM has an almost complete lack of reported adverse effects, provided the parameters are understood at least at a basic level. The remarkable range of medical benefits provided by PBM, has led some to suggest that it may be “too good to be true”. However one of the most general benefits of PBM that has recently emerged, is its pronounced anti-inflammatory effects. While the exact cellular signaling pathways responsible for this anti-inflammatory action are not yet completely understood, it is becoming clear that both local and systemic mechanisms are operating. The local reduction of edema, and reductions in markers of oxidative stress and pro-inflammatory cytokines are well established. However there also appears to be a systemic effect whereby light delivered to the body, can positively benefit distant tissues and organs.

I have to admit that Hamblin makes a strong case. But there is another side to the question. Hamblin himself uses that worrisome phrase “complementary and alternative medicine.” I have to wonder about thermal effects. We know that temperature can influence healing (that’s why people often use a heating pad). If photobiomodulation causes even a little heating, this might explain some of its effect.

I’ve talked a lot in this blog about websites or groups that debunk alternative medicine. Stephen Barrett of quackwatch looked at Low Level Laser Therapy in 2018, and concluded that “At this writing, the bottom line appears to be that LLLT devices may bring about temporary relief of some types of pain, but there’s no reason to believe that they will influence the course of any ailment or are more effective than standard forms of heat delivery.” Mark Crislip writing for Science Based Medicine in 2012 concluded “I suspect that time and careful studies on the efficacy of low level laser will have the same results as the last decade of acupuncture studies: there is no there there.” Jonathan Jarry wrote about “The Hype Around Photobiomodulation,” saying “That is not to say that all of PBM’s applications are hogwash or that future research will never produce more effective applications of it. But given biomedical research’s modest success rate these days and the ease of coming up with a molecular pathway that fits our wishes, we’re going to need more than mice studies and a plausible mechanism of action to see photobiomodulation in a more favourable light. A healthy skepticism is needed here, especially when it comes to claims of red light improving dementia.” 

What about clinical trials? An interesting one titled “Photobiomodulation Therapy is Not Better Than Placebo in Patients with Chronic Nonspecific Low Back Pain: A Randomised Placebo-Controlled Trial” was published in the journal PAIN in 2021 (Volume 162, Pages 1612–1620). It concluded “Photobiomodulation therapy was not better than placebo to reduce pain and disability in patients with chronic nonspecific LBP [low back pain].” The importance of a randomized, controlled study with an effective placebo is crucial. We need more of these types of studies.

Are Electromagnetic Fields Making Me Ill?

So, what’s the bottom line? In my book Are Electromagnetic Fields Making Me Ill?, I divided different medical devices, procedures, and hypotheses into three categories: Firmly Established, Questionable, and Improbable (basically: yes, maybe, and no). I would put photobiomodulation therapy in the maybe category, along with transcutaneous electrical nerve stimulation, bone healing using electromagnetic fields, and transcranial direct current stimulation. As a scientist, I’m skeptical about photobiomodulation therapy. But as dog lover, I’m using it every day to try and help Harvest’s hip dysplasia. This probably says more about how much I love Harvest than about my confidence in the technique. My advice is to not get your hopes up, and to follow your vet’s advice about traditional and better-established treatments. The good news: I don’t see much potential for side effects. Is it worth the money to purchase the device? My wife and I were willing to take a moderately expensive bet on a low probability outcome for Harvest’s sake. because she’s the goodest gurl. 

Mechanisms & History of Photobiomodulation with Dr. Michael Hamblin

https://www.youtube.com/watch?v=udnRpZ8l1_0

Source: http://hobbieroth.blogspot.com/2025/06/photobiomodulation.html