Deepest Penetration Red Light Therapy: Systemic Effects for Brain, Organ, and Deep Tissue Treatments

Red and Near-Infrared wavelengths of light are known to penetrate the deepest into the skin out of the entire sunlight spectrum.

However, can they reach important target tissues like muscles, bones, internal organs, and the brain? If they don't, can it have any effect on them?

Such questions would cast doubt on the efficacy of red light therapy. Often LED application can't reach very deep, Red wavelengths lack penetration, and not implementing skin contact method will severely limit penetration.

If the photons can't reach the target cells, many assume there would be no effect or benefit.

Photon Penetration vs Deeper Effects

We noted in a previous blog that Red and Near-Infrared (NIR) can reach anywhere from 1 to 50 mm into the skin, which depends not only on wavelength but also on intensity and how treatment is administered (skin contact or non-contact). Even if we say it "reaches" 50mm deep, the final intensity at that depth is greatly attenuated (diminished) to only trace amounts.

So, there are many cases where photon penetration would be insufficient to deliver enough dose to the deeper target tissues.

However, photobiomodulation studies often note Red and Near-Infrared (NIR) light benefits deeper than the actual photon penetration depth, or benefits completely different parts of the body than the area treated.

Such benefits and applications are identified in the literature as a variety of names including Systemic Effects, Indirect Effects, Abscopal Effects, Remote treatment, Global effects, or Bystander effects.

Leading researchers are now utilizing systemic targets and methods to improve red light therapy treatments, benefits, and our understanding of how red light therapy is really working.

In a recent interview on the ProNeuroLIGHT LLC YouTube channel, Dr. Hamblin says this:

"I think this is one of the key issues in photobiomodulation today, to what extent is the organ and the tissue you are shining the light the important thing, and to what extent is the systemic effect involving stem cells and blood irradiation."

So we should be paying attention to these systemic mechanisms we will cover in this blog as Dr. Hamblin recently notes as a key issue for modern photobiomodulation.

By understanding the systemic targets ourselves then we can utilize it properly to benefit tissues deeper into the body despite limited direct photon penetration.

Systemic Mechanisms:

We know the primary photo-chemical mechanisms of how photons are absorbed by intercellular structures like the mitochondria will up-regulate ATP production, NO release, Ca+ flux, increase Oxygen consumption, produce signalling ROS, form EZ water, and much more.

But what happens after that? Do these effects only occur inside the cell that the photon was absorbed?

Even a 1998 paper by Tuner and Hode discusses how the systemic effects of red light therapy can affect study designs.

"The effect of a laser beam is not limited to the site of optical diffusion. Through metabolic mediators, the effect can reach very distant parts of the body." [23]

How Systemic Effects Occur:

1. Promote NO release to increase circulation. [8]
2. Improve circulation and lymph movement [9]
3. Stem cell upregulation and release into the bloodstream [1]
4. Immune Cell modulation and upregulation [1]
5. Microbiome modulation (photobiomics) can affect the brain and immune system [7]
6. Stimulate the Cell-Free Mitochondria in the Blood [1]
7. Antioxidant production including subcellular melatonin production [2]
8. Cytokine and Growth Factor release from the cells [3]
9. Macrophages switch phenotype from pro-inflammatory to anti-inflammatory mechanisms. [video]

Activated metabolites in the cells will initiate signalling mechanisms and growth factor release as a cascade of benefits that often take place long after treatment has ended. As well stimulation to stem cells, immune cells, improved circulation, improved lymph movement, and stimulated mitochondria in the blood will carry benefits to other parts of the body.

Skin Improvements via Systemic Methods:

One randomized, double-blind, placebo controlled, split-face study used non-contact LED therapy for wrinkle treatment. They observed skin improvements in layers of the skin deeper than the theoretical penetration depth of 633nm.[3] This led them to comment on what they called the bystander effects of red light therapy.

 "healing had been observed in regions other than the directly irradiated sites,
suggesting that the bystander effect may also occur in beneficial biological events. The current understanding of the bystander effect is that irradiated cells may secret intercellular signaling molecules or that the gap junctional communication between irradiated cells and non-irradiated cells may play an important role in causing this phenomenon." [3]

Similarly, split-face trials for red light therapy can be challenging. A split-face trial is often used in facial care trials where the treatment is only applied to one half of the face. That way the untreated half of the face can remain as it's own control.

However, for red light therapy the systemic effects and bystander effects can cause improvements on the untreated side of the face. Which is why the previous study used both a true placebo group and a split-face treatment.

Here is what another LED skincare study discussed about the lack of placebo control in their split-face trial.

it is entirely possible that even the unirradiated side on the LED-irradiated subjects healed faster than a true unirradiated subject."[4]

It is a remarkable challenge that red light therapy is so effective; researchers have to take extra precautions to monitor if the systemic and bystander effects will interfere with their study design.

Blood Irradiation:

Light irradiation of the blood is a common therapy with PBM. One article notes that it has been used for decades in Russia, with the article focusing on how blood irradiation can improve Asthma.[20]

Blood irradiation is often shown to improve oxygenation of red blood cells. [13] In an early 2020 article, the cell-free mitochondria has discovered in the blood as another possible explanation of activation of the blood by photon absorption. [19] The article on Asthma discusses the improved antioxidant and immune response. [20]

Blood irradiation can be administered intravenously by a syringe with fiber optic tip to deliver the light directly onto the blood, or it can be done transdermally particularly targeting large veins near the surface of the skin (inner wrists, aorta artery behind the belly button, and jugular vein).

Intranasal Red Light Therapy (putting LEDs and lasers up the nose) is often considered to be a systemic treatment of the blood, although it is often marketed for targeting the base of the brain. The inner nostril is rich with blood flow (ever get a "nose bleed"?) so it is a valuable site for blood irradiation.

"Systemic effects of nostril-based intranasal irradiation via the blood cells and components could likely contribute to the observed neurotherapeutic effects (Hennessy and Hamblin, 2016). The tissue around the nasal cavity has abundant blood capillaries with relatively slow blood flow." [18]

One article recommends about 20 minutes of exposure for proper blood irradiation, much longer than the recommended exposure time for direct treatments.[14] This will be important later.

Another study recently published online in 2023 treated the left radial artery in the wrist for 20 female nurses with low back pain. They treated the wrist for 30 minutes with at 100mW laser resulting in 33 J/cm^2 total dose. [15] Imagine signing up for a trial to treat your chronic low back pain and then you get treatment to your wrist?

We can appreciate that using red light therapy anywhere on the skin will have some blood irradiation, so there is always some expected systemic effects regardless of treatment area and type as we already noted in the skincare trials.

Dr. Hamblin said this in the same interview: "wherever you shine the light in the body, you will be irradiating the blood, by definition"

Systemic Wound Healing:

A remarkable 2004 human study inflicted two identical 1.27cm^2 wounds on forearms of 22 participants (both male and female). Half were given multiple-wavelength LED/Laser therapy on only one wound, and the other half only had placebo treatment. The intensity was 75mW/cm^2, dose 8 J/cm^2, and treatment area of 19.2 cm^2. [17]

The study found that both wounds of the treatment group healed faster than the untreated group, even for the 2nd wound that wasn't irradiated.

The authors made this profound statement:

"They suggested that LLLT may have caused release of tissue growth factors into circulation, which may have affected surrounding tissues or entire systems. Indirect healing could be a very beneficial effect of this modality in treating tissue damage of large size or at multiple locations. It might also suggest that deeper tissues could be affected by light therapy."[17]

Another study found excellent systemic effects from 830nm for burn injuries.

"An extra bonus associated with LED-LLLT is the systemic effect whereby tissues distant to the irradiated site also benefit from the LLLT effect. A recent study clearly demonstrated the powerful systemic effect of 830 nm LED-LLLT, whereby indirectly treated burn injuries distant to the actual irradiated area healed significantly faster than unirradiated controls. ¹⁷⁾" [24]

Stem Cell Upregulation

It is commonly observed that treatment on bones near the surface of the skin like the tibia (shin bone) can stimulate stem cell production. These stem cells can enter the circulatory system and often confer whole-body systemic benefits as well the stem cells are often directed towards areas of pathology in the body.

One 2011 study showed that targeting rat tibia improved healing of their infarcted hearts, initiating the investigations into stem cell responses from targeting bones with PBM.[16]

A recent 2023 article targeted the legs and abdomen of rats inflicted with Parkinson's disease, and no treatment to the brain.[5] They made this statement about the results.

"the degree of neuroprotection provided by remote PBM was at least as, if not more, effective than transcranial PBM." [5]

They noted that the benefits from targeting the abdomen are also that adipose tissue contains a rich source of mesenchymal stem cells, so this is also a target mechanism for stem cell stimulation by PBM. [5]

Which we know that many people undergo stem cell therapies that extract their own stem cells from adipose tissue and re-inject it to heal injured areas. Perhaps PBM can be a low cost indirect method of stem cell treatment for the body.

Brain Treatments Through Systemic Therapy

Leading researchers on red light therapy to the brain like Michael Hamblin and John Mitrofanis will often write about the systemic effects.

In one article, Dr. Hamblin writes: "It is in fact very likely that the beneficial effects of PBM on the brain cannot be entirely explained by penetration of photons through the scalp and skull into the brain itself. "[11] Referring to to the systemic effects and the lack of penetration to the brain.

They recognize that only 1-3% of the Red/NIR light can penetrate the scalp and scull, with minimal light reaching the midbrain regions.[10] Yet, treatment certainly benefits the brain. So they have to understand the systemic mechanisms to explain the effects, as well they can utilize knowledge of systemic targets to improve brain treatments.

A recent 2021 review article titled "Exploring the Use of Intracranial and Extracranial (Remote) Photobiomodulation Devices in Parkinson's Disease: A Comparison of Direct and Indirect Systemic Stimulations" is a very important article for understanding the systemic mechanisms for brain health. [10]

The article concluded the following:

"The direct stimulation may form the primary mechanism of neuroprotection, while the indirect systemic stimulation forms a secondary and complementary mechanism. We propose that for a maximal neuroprotective impact both types of stimulation should be activated, and both be working together."[10]

So, directly targeting the head is still the most important aspect of treatment for the brain. However, there could be systemic mechanisms at play with blood absoption in the scalp and stem cell activation in the skull bone. Since that is where 97-99% of the photons would be absorbed with only 1-3% reaching the brain itself.

Dr. Hamblin states: "when you put the light on the head, first of all it has to go through the scalp and there is a lot of blood flowing in the scalp. Then it has to go through the skull and theres a lot of bone marrow in the skull. So by definition before the photons get into the brain they have to go through the blood and the bone marrow."

So essentially targeting the head and the scalp can have simultaneous systemic effects and direct effects for the small amount that reaches the brain.

Cells with high mitochondria counts will be more responsive to red light therapy. This means they can benefit from low doses, but also will be more sensitive to biphasic dose response, overdose, or overheating. So indirect treatments could be safer in the long run.

We can see that brain disease treatments can be enhanced by targeting the gut, adipose tissue, tibia, and bloodstream as "remote" and systemic targets.

Kidney Disease Indirect Treatment

One 2022 review article on the prospects of PBM to improve Kidney health summarizes the importance of considering systemic and remote treatment methods.[12]

They recognize to target the kidney would have skin, muscle, bone, and fat in the way hindering direct photons reaching the kidney itself. Yet directly treating over the kidneys and absorption into nearby fat and muscles can reduce inflammation and still confer healing. [12]

"PBM can also provide protective effect through indirect systemic effects such as immune/inflammatory response or activation of secondary messenger pathways and transcription factors." [12]

They give a quick list of 13 articles showing systemic indirect responses for cardiovascular disease, diabetic retinopathy, Alziemer's, Parkinson's, lung injury, and depression.[12]

And they remind us that combining direct and systemic treatment methods can improve benefits and outcomes.

Combatting a Virus

Another recent January 2023 study used only 2.9 mW/cm^2 intensity 940nm LED vest covering the chest and abdomen for 15 minutes to treat a recent novel coronavirus of unknown origin.[21]

Many would assume this treatment would lack penetration due to the low intensity, usage of LEDs, and longer wavelength used that has higher water absorption. However, the study was successful in reducing systemic inflammation and cardiopulmonary issues typically associated with the virus.[21]

The authors don't speculate on the mechanisms, but they note many other studies that also confirm their findings of a systemic reduction of inflammation particularly with this type of virus. The results of this study were also reviewed on this popular MedCram YouTube Channel. We give our perspective on our own YouTube channel.

Another recent study published April 2023 used either a transcranial 1070nm helmet or a 660/850nm full-body bed to treat brain fog from long covid (post covid) symptoms. [22]  Although they assumed the direct helmet treatment would perform better, both treatments performed nearly equally. Both devices delivered 24mW/cm^2 intensity for 14 minute treatments 3 times a week for 4 consecutive weeks. Although both had the same dose in J/cm^2, the bed delivered about 27 times more total energy because it covers much more body area. The full-body bed showed slightly better improvement over the helmet, but it was not statistically significant. [22] But it could be said the systemic effect of full-body irradiation was why it was able to be as good or even slightly better than the direct treatment.

How to use Systemic Therapy?

Here are a few tips to enhance red light therapy treatments with systemic treatments.

1. Always target as close as possible to the injured area or area you are trying to improve. For example, even if the photons don't directly reach the brain or gut or muscle or other deep organs, still treat directly over those areas because that gives you the best bystander effects. If there are bandages or clothes or hair or other barriers, then treat the bare skin as close as possible to the injured site.

2. Target "remote" areas for systemic benefits as a compliment to direct treatments. For example it is becoming commonplace for chronic brain diseases to not only treat the head directly, but also treat the gut and tibia for systemic support. Check out our other article on other areas to target for systemic full-body benefits.

3. Even though non-contact red light therapy (treatments at a distance and not with skin-contact) is inherently superficial absorption, they can still benefit deeper into the body via these systemic mechanisms. Use reasonable dosages and intensities and have patience with the systemic and cumulative dose responses over time.

4. The wavelengths and penetration depths may be of secondary importance, as long as you are treating in the therapeutic window of 600nm-1100nm. Deeper penetration depth does not always mean better benefits, we need to understand the activation of more superficial systemic pathways to understand the true benefits of red light therapy.

5. Using multiple-wavelengths particularly combinging Red and Near-Infrared often shows improved results over single-wavelength irradiation for a wide variety of applications. This could be explained now by the activation of multiple systemic mechanisms, and not just from direct penetration. Read more about multiple-wavelength treatments in this blog.

Non-Contact Full-Body LED Red Light Therapy is a Systemic Therapy:

Utilizing non-contact red light therapy (like full-body panels) can certainly have deeper effects despite its apparent lack of penetration. However, users must be clearminded of the real target is the blood and systemic effects.

Dr. Hamblin notes:

"As time goes on, the systemic effects of photobiomodulation are becoming more well accepted. You know one of these reasons for this is that the whole field is moving away from what used to be laser therapy when people had a focused laser beam and they shone it as a point on a joint or a wound or something... into large area LED arrays and large area LED arrays is certainly deliver a lot more systemic photobiomodulation than a focused laser beam."

Dr. Hamblin reminds us we have to consider large non-contact LED panels and LED beds as more of a systemic treatment, since we know the direct penetration can be limited due to a lack of skin contact application and not being a focused laser beam.

For proper dosing, activating systemic mechanisms seems to have a minumum amount of exposure time, perhaps to get enough exposure into the circulating bloodstream and to initiate the signalling mechanisms. It is an interesting coincidence that the 20 minutes recommended for blood irradiation is also a common effective dosing time for non-contact full-body LED red light therapy.

Which may help confirm that non-contact LED full-body light therapy is indeed a systemic therapy that needs adequate exposure time to impact the circulating blood and activate systemic mechanisms.

Ironically, we could say "full body light therapy" doesn't directly treat anything at all, it is mostly targeting superficial and systemic mechanisms.

A good compliment to a large red light therapy panel which delivers systemic therapy would be a torch (flashlight) or handheld cluster for direct skin contact. This way we can combine the indirect benefits of full-body panels plus the direct treatment pathways as recommended to benefit deeper organs and tissues.

Rather than people endlessly wasting money on oversized modular panel setups, getting a moderate-sized body-light panel plus a smaller direct contact device is much more efficient and cost effective to optimize treatments to combine both direct and indirect therapies at home.

Conclusions:

In a previous blog we uncovered the myth that Far-Infrared is often falsely claimed to reach 3-4 inches into the body. We know the actual photon penetration is very shallow from water absorption, but the benefits observed are 3-4 inches into the body.  Far-infrared sauna also clearly offers full body benefits like for cardiovascular health and brain health despite limited photon penetration.

And none can deny that UV-B absorption, which is very superficial, helps synthesis of Vitamin D which is crucial for whole body health and function. Our skin certainly does not play a passive role in how it blocks and filters light, it plays an active role in bringing the benefits of light deeper into the body.

Observations of systemic and remote benefits of Red & NIR Light Therapy have been commonplace for decades. But many mechanisms are still being recently discovered or speculated about. Which often makes it hard to believe until we fully understand the mechanisms.

Yet now it seems more logical that many of the benefits of Red and NIR are conveyed by indirect and systemic mechanisms, rather than direct penetration.

As mentioned in our previous blog on penetration depths, it is not advised to use excessively high power or intensity for the sake of deep penetration at the risk of damaging the skin. We can utilize a combination of direct targeting and systemic targets as a safer and more balanced approach.

By using direct targeting and systemic targets combined then we can find safe and effective ways to treat the deepest regions of the body, even if there is often an apparent lack of photon penetration.

[1]

[2]

Zimmerman, S. and Reiter, R. 2019. Melatonin and the Optics of the Human Body. Melatonin Research. 2, 1 (Feb. 2019), 138-160. DOI:https://doi.org/https://doi.org/10.32794/mr11250016.

[3]

[4]

[19]