biphasic dose response, cumulative dose response, dosing, how often, red light therapy - April 10, 2022

How Often Should We Use Red Light Therapy? The Hidden Secrets of Cumulative Dose

How often should we use our Red Light Therapy panels? Can we use them multiple times a day? Do we need a break from using them too often?

To figure out how often to use red light therapy, we must understand important concepts like the Cumulative Dose and Rest Periods between doses. We will dive into the important mechanisms of how red light therapy works after a treatment has ended.

Although these concepts seem to be common-knowledge in the scientific literature, we have seen very little coverage of these important aspects of proper dosing protocols in other blogs.

We will cover:

Cumulative Dose definition for Red Light Therapy.
The cellular effects that happen after a treatment.
The Importance of Rest Time Between Doses .
How dosing too often leads to an inhibitory biphasic response.
Clinical examples of different dosing intervals for hair, skin, brain, and full body.

Perhaps you received a red light therapy device with some guidance for the distance to stand away from the panel and how long to use the panel. However, the guidelines on “How Often” we should use a red light therapy panel at home often seems vague.

By now, many of our readers appreciate the intricacies of intensity, time, energy fluence, and even skin contact for an effective dose of red light therapy. However, it is often only implied that Red Light Therapy should be administered at a routine interval.

One study that we will be referencing explains it nicely:

“While selection of the correct wavelength and power density (W/cm2) is important, consistent application of the necessary dose (energy density or fluence: in joules per cm2 [J/cm2]) is required if the best therapeutic effects are to be achieved.” [1]

This is a profound statement that reminds us that we need consistent applications of red light therapy to achieve the best benefits, and perhaps we often get too fixated on the individual parameters of a single dose.

But now we have opened yet another can of worms. It begs the question of what we define as “consistent application”?

Should we do red light therapy only once a day or can we do it twice a day? Is 3 times a day is too much? Perhaps we should only do it once every other day? Once a week? Or once a month?

Remember the Biphasic Dose response of Red Light Therapy tells us that too little of a dose leads to no response, but too much leads to an inhibitory response. We usually want to stay in the beneficial middle-range called the stimulatory response.

Does the Biphasic Dose Response play a role in how often we should use Red Light Therapy? Logically, if we do 10 doses a day, that seems like too much. Will the cumulative dose force us to cross the threshold into a lack of benefits?

Looking at it another way, we ask how long should we wait in between red light therapy treatments? If we “pause” a treatment for 5 minutes and then return to finish it, then logically we would consider that as a continuation of the original treatment. If we wait 12 hours to return to the treatment, then perhaps that is a new dose all together.

This helps formulate our concept and definition of Cumulative dose for red light therapy. Where the cumulative dose describes the raising level of red light therapy effects that accumulates across multiple doses during a relatively short time span.

Cumulative dose is probably a new term for most people in this Red Light Panel industry, since it also implies that we need to restrain ourselves from excessive treatments or too high of a dose. Which may hurt the bottom line of some business models that promote “more is better”.

Although the dosing interval has not been thoroughly studied in the science, once again we have dug up many interesting articles that can help us provide a framework of understanding of this important aspect of Red Light Therapy dosimetry.

What is the Cumulative Dose effect for Red Light Therapy?

Let’s jump right into defining and explaining what the Cumulative Dose is, since that is the crux of what we need to understand for the correct dosing interval.

Cumulative Dose tells us that there is a building or stacking of effects in the body that accumulate across separate treatments. Especially if doses of red light therapy are administered multiple times in one day or on consecutive days.

One study informally defines the cumulative dose as:

“The dose from one treatment lasts some time and what “remains” of the dose is added to the dose at the next treatment. Adequate time between doses is essential to allow the cells time to respond to the initial dose and will also avoid a situation where the accumulated dose eventually ends up above the bio-stimulating range or even in the bioinhibitory range, with consequently poorer results.” [1]

Another study tells us this about cumulative dose:

“this therapy produces effects on muscle tissue lasting 24 to 48 hours, suggesting possible cumulative effects if applied repetitively.” [2]

Now that we have roughly defined what Cumulative Dose is, let’s take a look at some of the science that explains why it is so important.

What Happens after a Single Dose of Red Light Therapy?

Thinking about Cumulative Dose forces us to appreciate that Red Light Therapy is doing its work in our cells long AFTER the treatment session has ended. The typical western mindset makes us assume we are only getting benefits DURING the treatment, but this certainly is not the case.

Remember that upregulated Adenosine Triphosphate (ATP) production in the mitochondria is the principal mechanism of benefits for doing red light therapy in the first place. However, has anyone told you that the ATP increase not only happens during treatment, but ATP production is increasing to a peak at about 6 hours after the Red light therapy session ended? They can still find remains of the effects of the LED therapy up to 24 to 48 hours after the dose was administered! [2] [3]

Cytochrome C Oxidase (CCO) enzyme activity is also considered a primary mechanism for red light therapy. Researchers have repeatedly found elevated activity of CCO for 24 hours AFTER treatment ended. [4]

Even more metabolites of red light therapy effects found 24-48 hours after treatments include Nitric Oxide (NO), Heat Shock Protein (Hsp70), Interleukin-2 (IL-2) and Calcium release. [1][5]

Some studies have graphed or visualized the cellular response in a similar way that we show below.

Red Light Therapy Cellular Effects after Single Dose

In the graph above, after a single dose of Red Light Therapy there are several cellular responses that peak several hours after treatment. Then the response tends to diminish back to baseline after about 48 hours. Keep this graph in mind for the next section.

Cumulative Response and Rest Periods between Doses

Similar to the rest periods between exercise, where after exercise many of the repair mechanisms take place for building muscle tissue – we should also be considering rest periods between red light therapy doses.

Let’s say we are doing a daily dose of red light therapy, exactly every 24 hours we do another dose. According to our theory in the previous section, many of the cellular responses like ATP, CCO, NO, and Calcium are still at an elevated level. Since it perhaps takes over 48 hours for those effects to subside.

Now we have a building of these cellular responses and the cumulative dose starts to take over.

Cumulative Dose Red Light Therapy Biphasic Dose Response How Often Red Light Therapy

The graph above, which is similar to the graphs seen in PocketDentistry.com and this study, shows us how the cumulative dose of stacking cellular effects could start to cross the line into the inhibitory region. [1]

Ideally, if the doses are adequately spaced apart, there is less risk of the Cumulative dose crossing the line to the cellular inhibition range.

Risks of Too Dosing too Often – Biphasic Response

Several studies, usually longer-term studies, have mentioned that they are particularly mindful of not allowing the cumulative dose to reach a point of cellular inhibition, meaning they crossed the line to the higher end of the biphasic dose response.

For our all-important ATP production, one study noticed a biphasic dose response as the cumulative dose progressed. Obviously, it is quite important to keep our most important biomarker of red light therapy effectiveness in the stimulatory range.

“The ATP results support published findings that suggest that the cumulative dose administered determines the biostimulatory or bioinhibitory effect of the laser irradiation.” [1]

One long term study on muscle performance had this to say about the possible negative response from the cumulative dose.

“It could be envisaged that cumulative exposure or excessive light doses could produce an inhibition or a lack of positive effects on human skeletal muscles based on the biphasic dose response” [2]

Another study mentions the possible danger of the suppressive effects when a treatment is administered repeatedly (chronically) every other day for 30 days.

“…showing the depletion in the adaptive cell response under increased cumulative dose. Similar effects were observed for the NO and IL-2 production. Taken together, these dose response relationships show the risks of possible danger of chronic treatment with the low-energy laser light.” [5]

Another study has noticed the potential issue that clinical doses combined with too much sunlight exposure in one’s daily lifestyle may affect the cumulative dose, thus leading to a biphasic dose response.

“Equally, the potential of sunlight to deliver significant light doses of red to near-infrared wavelengths means that additional exposure to sunlight might need to be restricted when using LED or laser light sources to deliver controlled light doses. Given the reported biphasic response of some models to light therapy (Huang et al., 2011), too much light may be as ineffective (and possibly even detrimental) as too little light. We think that this is a potentially important aspect of light therapy that has been somewhat overlooked with respect to clinical use.” [6]

As far as we can tell, the cumulative dose response has indeed been largely overlooked in the current state of this industry.

Short-Term vs Long-Term studies Dosing

Many studies on red light therapy have been short-term, and have used higher doses to illicit a healing response in just a few treatments. Which is a big opportunity for manufacturers to cherry-pick the higher-intensity and higher-dose studies to sell their overpowered products.

However, with the cumulative dose and biphasic dose response in mind, some researchers reconsider the intensity and dose to lower levels when designing longer-term studies.

One study noted that while a single treatment for TBI in rats was effective at 50mW/cm^2 and 36 J/cm^2, for the longer-term study they decided to use only 25 mW/cm^2 and 18 J/cm^2 per dose. [7] That is a dramatic difference of cutting the dose and intensity per session in half, simply because the researchers were concerned of the biphasic dose response of the cumulative doses.

This is also very clever because they acknowledge the importance of time and they didn’t want to simply cut the dose and the time in half. They wanted to cut the dose in half, but keep the time the same. So, they also reduced the intensity.

These are a very important considerations, that using a device longer-term (like a red light panel that you own at home and plan you use for many years) should consider either spacing the dose apart further, or decreasing the intensity and dosage. Whereas most of the dosing recommendations you have received so far have likely come from shorter term studies so companies can upsell you on higher intensity products.

Practical Applications of Cumulative Dose – Hair, Skin, Athletics, Brain, and Full Body treatments

Not to worry, most human studies on Red Light Therapy do not report negative outcomes based on cumulative dose response. As shown earlier, researchers are mindfully designing their protocols appropriately to avoid too much cumulative dose.

Here we will take note of a few long-term studies and how often they used their devices.

Hair Growth Dosing Interval:

Hairs are fickle little buggers and hair growth clearly something that requires a long-term treatment protocol. It is the perfect example to consider cumulative dose! Naturally, we don’t want too much of a dose which would inhibit growth. The blog over at OverMachoGrande covers this very well and introduces many of the concepts that we also have covered in this blog.

A more recent review article of home-use hair restoration caps shows that nearly all of them recommend dosing every other day. [8] Not daily, since that could be too much and inhibit hair growth.

Skin Dosing Interval:

A recent long-term at-home study for reducing wrinkles around the neck used daily dosage frequency. They reported an improvement in skin, but more importantly noted that there was no long-term issues for thyroid function. Now that you understand the cumulative response, this is a very good thing that the thyroid was safe for daily treatments of red light therapy in this case. [9]

Athletic Performance Interval:

In a review article on athletic performance, the long-term studies tended to do treatments 2 to 3 times per week. [10] Perhaps this isn’t necessarily because of the cumulative dose response, but more for convenience of doing the treatments in conjunction with the training regimen. We will need to see more studies in the future with at-home devices for muscle recovery and athletic performance.

In general, it seems research does the red light therapy treatments in conjunction with the same day as exercise to help maximize the benefits for both. So if you work out 5 or 7 times a week, then it makes sense to do red light therapy just as often as exercise.

Brain Interval:

There are some studies with Vielight that were administered daily at home. [11] However, there is another study that really highlights the cumulative response.

One study treated aged rats and young rats daily for 58 days. The aged rat brains showed CCO activity improvement after the course of treatment, while the young rats showed the opposite effect. The researchers assumed the young rats already had elevated CCO activity and the biphasic dose response caused a suppressive effect on them. [12]

This is an important distinction that healthy, young people likely would need less dosage, else would reach an inhibitory dose especially with cumulative doses.

At Home Devices Review:

One publication reviewed all articles on at-home usage of red light therapy. They noted that most of the treatments were done daily. Although one study was done twice a day and another was 3 times a day. [11]

Full-Body Red Light Bed Interval:

The only long-term study protocol (just a protocol, not yet conducted) for full-body light therapy plans to use a full-body pod to treat fibromyalgia syndrome 3 times a week. [13] Obviously, they haven’t completed the study yet, but at least this shows the researchers have confidence that 3 treatments per week should be sufficient to treat this condition.

However, we might assume they only do 3 times a week for the convenience of the patients to not have to drive to the clinic too often. Perhaps if they had at-home units they might want to do it more often.

Conclusions

In the course of understanding "how often" we should do red light therapy revealed some very important concepts. We learned about the cumulative response, cellular effects after treatment, biphasic doses across multiple treatments, how longer-term treatments may reduce the intensity or dose per treatment, and looked at some real examples of long-term repeated dosing protocols.

Here are a few of the conclusions of optimal dosage protocols we can be confident about:

Optimal benefits of red light therapy come from routine usage.
Many cellular mechanisms like ATP production are active after treatment, not just during treatment.
The Cumulative dose is the building of effects across separate treatments.
Chronic or too repetitive doses will cross to inhibitory effects in accordance with the biphasic dose response.
Daily usage of red light therapy is common for at-home trials. For some conditions 2 to 3 times per day is appropriate.
Reducing the intensity for long-term usage is important compared to short-term doses we commonly see are higher.
As little as 2 to 3 times a week is certainly effective in many studies.
Some conditions like hair growth are important to space out to every other day to avoid inhibition.
Healthy, young individuals should consider lower doses and longer spacing between doses to avoid biphasic dose response.

We postulate that many of the “high intensity” panels on the market may give customers instant gratification with feelings of warmth and benefits that come quickly. However, they should be mindful of the long-term effects of repeated usage, and take note if there is a decline in those benefits over time. That would be the inhibition taking over per the cumulative dose concepts we learned here.

While there still is a lot we need to learn about proper dosing protocols, it is clear that daily usage of low intensity red light therapy can be the ideal way to do treatments. If you are short on time or do higher intensity, then perhaps only 2-3 times a week is sufficient. Typically for only severe or acute issues would do treatments more than once a day.

As with most of our blogs, it is a story of moderation with dosing red light therapy. This time we need to consider how red light therapy affects us across multiple doses with long-term usage. We don’t always give you an exact prescription, but these are important mechanisms to be aware of so you can customize your dose to make red light therapy work for you.

References:

[1]

Hawkins D, Abrahamse H. Effect of multiple exposures of low-level laser therapy on the cellular responses of wounded human skin fibroblasts. Photomed Laser Surg. 2006 Dec;24(6):705-14. doi: 10.1089/pho.2006.24.705. PMID: 17199470.

https://pubmed.ncbi.nlm.nih.gov/17199470/

[2]

Ferraresi, Cleber et al. “Effects of Light-Emitting Diode Therapy on Muscle Hypertrophy, Gene Expression, Performance, Damage, and Delayed-Onset Muscle Soreness: Case-control Study with a Pair of Identical Twins.” American journal of physical medicine & rehabilitation vol. 95,10 (2016): 746-57. doi:10.1097/PHM.0000000000000490

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026559/

[3]

Ferraresi C, de Sousa MV, Huang YY, Bagnato VS, Parizotto NA, Hamblin MR. Time response of increases in ATP and muscle resistance to fatigue after low-level laser (light) therapy (LLLT) in mice. Lasers Med Sci. 2015 May;30(4):1259-67. doi: 10.1007/s10103-015-1723-8. Epub 2015 Feb 21. PMID: 25700769.

https://pubmed.ncbi.nlm.nih.gov/25700769/

[4]

Albuquerque-Pontes GM, Vieira RP, Tomazoni SS, Caires CO, Nemeth V, Vanin AA, Santos LA, Pinto HD, Marcos RL, Bjordal JM, de Carvalho Pde T, Leal-Junior EC. Effect of pre-irradiation with different doses, wavelengths, and application intervals of low-level laser therapy on cytochrome c oxidase activity in intact skeletal muscle of rats. Lasers Med Sci. 2015 Jan;30(1):59-66. doi: 10.1007/s10103-014-1616-2. Epub 2014 Jun 24. PMID: 24957189.

https://pubmed.ncbi.nlm.nih.gov/24957189/

[5]

Novoselova EG, Glushkova OV, Cherenkov DA, Chudnovsky VM, Fesenko EE. Effects of low-power laser radiation on mice immunity. Photodermatol Photoimmunol Photomed. 2006 Feb;22(1):33-8. doi: 10.1111/j.1600-0781.2006.00191.x. PMID: 16436179.

https://pubmed.ncbi.nlm.nih.gov/16436179/

[6]

A New Perspective on Delivery of Red-Near-Infrared Light Therapy for Disorders of the Brain

Published on September 19, 2016

Author: Nathan S. Hart

Specialty: Neuroscience
Institution: Experimental and Regenerative Neurosciences, School of Animal Biology, University of Western Australia
Address: Perth, Western Australia, Australia
Institution: Department of Biological Sciences, Macquarie University
Address: North Ryde, New South Wales, Australia

Author: Melinda Fitzgerald

Specialty: Neuroscience, Neurology
Institution: Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia
Address: Crawley, Western Australia, 6009, Australia

https://www.discoverymedicine.com/Nathan-S-Hart/2016/09/a-new-perspective-on-delivery-of-red-near-infrared-light-therapy-for-disorders-of-the-brain/

[7]

Xuan, Weijun et al. “Repeated transcranial low-level laser therapy for traumatic brain injury in mice: biphasic dose response and long-term treatment outcome.” Journal of biophotonics vol. 9,11-12 (2016): 1263-1272. doi:10.1002/jbio.201500336

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025344/

[8]

Lueangarun, Suparuj et al. “A Systematic Review and Meta-analysis of Randomized Controlled Trials of United States Food and Drug Administration-Approved, Home-use, Low-Level Light/Laser Therapy Devices for Pattern Hair Loss: Device Design and Technology.” The Journal of clinical and aesthetic dermatology vol. 14,11 (2021): E64-E75.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675345/

[9]

Lee, Young In et al. “The Use of a Light-Emitting Diode Device for Neck Rejuvenation and Its Safety on Thyroid Glands.” Journal of clinical medicine vol. 10,8 1774. 19 Apr. 2021, doi:10.3390/jcm10081774

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073506/

[10]

Ferraresi, Cleber et al. “Photobiomodulation in human muscle tissue: an advantage in sports performance?.” Journal of biophotonics vol. 9,11-12 (2016): 1273-1299. doi:10.1002/jbio.201600176

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167494/

[11]

Gavish L, Houreld NN. Therapeutic Efficacy of Home-Use Photobiomodulation Devices: A Systematic Literature Review. Photobiomodul Photomed Laser Surg. 2019 Jan;37(1):4-16. doi: 10.1089/photob.2018.4512. PMID: 31050938.

https://pubmed.ncbi.nlm.nih.gov/31050938/

[12]

Cardoso, Fabrízio Dos Santos et al. “Photobiomodulation of Cytochrome c Oxidase by Chronic Transcranial Laser in Young and Aged Brains.” Frontiers in neuroscience vol. 16 818005. 18 Mar. 2022, doi:10.3389/fnins.2022.818005

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971717/

[13]

Navarro-Ledesma S, Gonzalez-Muñoz A, Carroll J, Burton P. Short- and long-term effects of whole-body photobiomodulation on pain, functionality, tissue quality, central sensitisation and psychological factors in a population suffering from fibromyalgia: protocol for a triple-blinded randomised clinical trial. Ther Adv Chronic Dis. 2022 Feb 21;13:20406223221078095. doi: 10.1177/20406223221078095. PMID: 35222905; PMCID: PMC8864274.

https://pubmed.ncbi.nlm.nih.gov/35222905/

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