The Safety and Benefits of Overdosing Red Light Therapy: Cellular Inhibition and Apoptosis

The Safety and Benefits of Overdosing Red Light Therapy: Cellular Inhibition and Apoptosis

Is overdosing Red Light Therapy safe? How much harm can overdosing red light therapy cause? Should it be avoided at all costs? Or can it be utilized in specific contexts for alternative medical applications with minimal side effects?

High doses of Red Light Therapy are reported to cause mitochondrial or cellular inhibition, which is the opposite effect that we typically want from the therapy. 

"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." [1]

Excessive overdosing red light therapy will greatly increase ROS to trigger apoptosis (cell death). 

"In summary, LLLT at lower energy range inhibits apoptosis but paradoxically promotes apoptosis at a higher energy range." [2]

Overdosing red light therapy currently appears to be generally safe with negligible DNA damage (i.e. no risk of cancer inducing effects so far). [11][12]

High doses often temporarily inhibit function, they do not generally cause damage. This is a reversible effect. Meaning the functionality returns to normal after some period of time. 

After an overdose, one could wait for a washout period of 2-5 days before resuming to normal low doses. A singular, inadvertent overdose would not be expected to cause any permanent harm. 

Reported acute side effects of overdosing are temporary pain, skin redness (erythema), edema (swelling), and hyperpigmentation. Typically these are short term effects and resolve after a few hours or days. [3] [4]

Note that human experiments on overdosing have been only on targeted spots, we don't yet know the side effects of whole body overdosing. 

Also, there are no long-term studies on chronically overdosing red light therapy. There are many indications that repeated overdosing of Red/NIR light therapy would lead to long term effects like advanced photoaging of the skin. [5]

"Furthermore, while PBM has been found to be harmless in numerous studies, its long-term effects, particularly when applied to ongoing treatment for atopic disorders, require thorough examination. The risk of tissue overheating, unintended stimulation of proinflammatory pathways, and the possibility of reduced efficacy with prolonged use are all possible concerns." [6]

To learn about overdosing red light therapy, we can examine studies that purposely use high doses for clinical applications. There is a small field of research that purposely inhibits unwanted cells or functions. This is therapeutically advantageous in many contexts such as:

  • Inhibiting fibroblast activity to reduce scar formation
  • Inhibiting nerve cells for temporary pain relief (analgesia)
  • Suppress overactive immune cells like in psoriasis and eczema 
  • Slowing or killing cancer cell proliferation or viability

Medical Disclaimer: Examining these medical applications is for educational purposes only. Please review with a doctor before applying Red Light Therapy for medical conditions. 

Researchers understand that inhibitory overdoses of red light therapy exist since they are purposely using them for unique benefits. However, this is currently only a small set of promising studies so far. 

"Dose" vs Fluence:

Fluence is the appropriate term for Energy Density; the amount of radiant energy absorbed per unit area. In Photobiomodulation, the common unit for fluence is Joules Per Centimeter Squared (J/cm^2).

The fluence is often incorrectly referred to as the "dose" of Red Light Therapy. Hence, we use quotes when using the word "dose" to refer to fluence. The term fluence is more accurate, but we often use "dose" since it is a term more people will be familiar with in the current vernacular.

Since it will be too distracting in this blog to use quotes every time, we are also dropping the usage of quotes when referring to dose as fluence (J/cm^2).

High Fluence Low Power Laser Therapy (HF-LPLT)

This blog will be discussing the effects of high dose (J/cm^2) red light therapy. 

More precisely, studies have often called this technique High Fluence Low Power Laser Therapy. Abbreviated to HF-LPLT. More recent studies have also used LED. 

HF-LPLT also uses low powers or intensities similar to PBM and LLLT. This is an important underlying assumption for the rest of this blog. The high doses are being delivered with minimal heat and relatively low intensity as the main reason why this technique is very safe. 

The general range of PBM fluences are under 50 J/cm^2, where higher fluence is associated with inhibition and/or apoptosis. 

"The second important factor is energy density. In general, lower energy density (0.05 J/cm2–10 J/cm2) promotes cell proliferation, while higher energy density (above 50 J/cm2) enhances apoptotic processes." [7]

One article describes this High Fluence Low Power Laser Therapy as:

"Fluence, according to the International System of Units, is the energy density integrated over the unit surface of a sphere. Just like PBM using low fluences of light, high-fluence low-power laser irradiation (HF-LPLI) stimulates mitochondrial chromophores, but this time it overstimulates them, which in turn activates the mitochondrial apoptosis pathway, altering the cell cycle, inhibiting cell proliferation and even causing cell death. HF-LPLI (usually fluences above 80 J cm−2)" [8]

Other quotes on High Dose red light therapy establish even higher thresholds:

"High-fluence LED-RL phototherapy is phototherapy with fluence >160 J/cm2 per treatment session. " [9]

And:

"However, our laboratory team has studied the inhibitory properties of red light greater or equal to 320 J/cm2 to treat pathological hyperproliferative processes, including fibrosis " [10]

Thus, there is no definitive threshold for "high" dose or "overdosing" red light therapy. The above quotes indicate it may be greater than 50, 80, 160, or 320 J/cm^2. The threshold of "high" dose may depend on the specific type of cell being treated, the pathology, and the level of intended inhibition or apoptosis. 

DNA Safety of High Fluence Red Light Therapy:

Many of the preliminary studies on High Fluence have focused on establishing safety. Like most therapies, the benefits must outweigh the risks. 

Two articles investigated if overdosing Red and Near-Infrared light would induce DNA damage. [11][12] Checking if overdosing red light therapy could be a risk for causing cancer. 

They found that markers of DNA damage were insignificant with Red and NIR light up to doses of 1280 J/cm^2 (Red) and 264 J/cm^2 (NIR). [11][12] These were the maximum doses tested in each study. It is possible they did not yet find a threshold where damage could theoretically occur. 

However, they note that their studies were done "in vitro". This means it was done on isolated cells (i.e. on a petri dish). 

"Future studies may confirm that no DNA damage occurs from RL in animal models and human subjects." [11]

The authors recommend future studies on whole living animals or humans, called an "in vivo" trial. As the complexity of a whole human or animal could yield different results than with isolated cells.

A review article of Light Therapy on the skin also reported these results:

"PBM applied through LLLT or LED is generally regarded as safe. RL and NIR light do not seem to induce DNA damage, even at fluences up to 1280 J/cm2." [56]

Human Study Scar Reduction from High Fluence Red Light Therapy

Fibroblasts are cells in the skin that produce important connective tissue like collagen and elastin. 

"Photobiomodulation (PBM) promotes fibroblast cell proliferation, migration, release of growth factors and wound healing." [13]

A main mechanism of stimulatory Photobiomodulation is that it increases fibroblast activity to produce tissues for wound healing, and for improving skin quality. [14]

However, overactive fibroblasts are responsible for forming scars (fibrosis). as they create excessive tissue. Scars can form in response to a skin injury (cut, wound, surgical scars), autoimmune condition, or infection. [15]

Many in vitro (isolated cells) HF-LPLT studies have confirmed that high doses will inhibit fibroblast activity. [16][17][18][19][20][21][22]

So while overdosing red light therapy may be bad for skincare or wound healing, it is good in the context of inhibiting overactive fibroblasts. 

"Our group has previously demonstrated that RL irradiation can significantly inhibit HDF proliferation and collagen production without significantly increasing apoptosis levels or altering gross cellular morphology" [11]

As the above quote confirms, the authors are confident they can inhibit collagen production without causing cell death or damage. This is an important point we will explore more later: the functions are often temporarily hindered by overdosing, but it does not cause cell death or damage. 

This research culminated towards a trial on humans. The treatment took place within one week after face-lift surgery to address the scar formation. It was a split-face design, so only one side of the face was actually treated and the opposite side used a placebo treatment.  [23]

They used a 633nm LED device with an intensity of 36mW/cm^2 at 10mm away from the skin. They had 3 different groups for dosing. One was 160 J/cm^2 (30min) , 320 J/cm^2 (60min) , and 480 J/cm^2 (90min).[23]

The results were subtle and not statistically significant, but the authors found enough safety and efficacy to recommend proceeding with more trials. 

"Because all doses displayed excellent tolerability and conferred improvements in multiple endpoints, all three doses merit further assessment in a phase III study."[23]

A recent June 2025 review article examined similar studies for reducing fibrosis from cancer treatments and side effects. They also emphasis utilizing higher doses for purposeful inhibitory fibroblast modulation. [55]

Pain Relief (analgesia) from High Dose Red Light Therapy

Photobiomodulation and LLLT has long been known to alleviate pain. However, there are two pathways this can be induced depending on the dosage.

  • Low Doses: reduce inflammation and promote healing for longer term pain relief
  • High Doses: inhibit nerve signaling to temporarily reduce pain sensations

*as always, the effects are not cleanly binary but are on a gradient with a lot of overlap.

Similar to taking an Asprin drug for relieving pain. High Dose red light therapy will inhibit pain signals but not necessarily address the root cause of the problem. In contrast, low doses may not have immediate pain relief, but can address the longer-term issue like reducing inflammation and promoting healing. 

"Using light to block nociceptor activity is a notably different approach than most other PBM research that focuses on stimulating cell processes such as anti-inflammation, vascular perfusion, and ATP production to treat pain,. Selective inhibition is achieved using higher irradiances and fluences than standard PBM at the neural target, but can otherwise consist of similar total energies as standard PBM and is fundamentally light-based (and presumably not heat-based)." [24]

As the above quote describes, using high fluence to block nerve activity is a different approach than conventional PBM techniques. 

Thus, some rodent studies have used 180 J/cm^2 [25] , 1833.6 J/cm2, 611.2 J/cm2 [26] to provoke nerve inhibition for pain relief. Often directly exposing the nerve to the laser to these high doses (not through the skin). 

One human study had 44 people use laser treatment before a tooth extraction.  The laser was a 1064nm pulsed laser delivering a pulsed dose of 73-107 J/cm^2. This was compared to standard numbing agents. They found the laser treatment performed statistically similar to the numbing agent for blocking pain. [27]

Pain relief from high dose red light therapy is more akin to a numbing agent, and not necessarily utilized for long-term healing like conventional low-dose Photobiomodulation. Although this is revolutionary as the pain relief is immediate and without drugs or needles. 

Overdosing Red Light Therapy is Temporary and Reversible

It is important to note the mechanism of high doses on nerve cells is not to cause damage, but to temporarily inhibit their activity. As noted in the following 3 quotes.

"PBM changes are reversible with no side effects or nerve damage." [28]

And:

"Our data showing suppression of firing without producing nerve damage support these studies." [29]

And:

"Treatment with PBM, using relatively high-energy densities, is often used to elicit an analgesic effect. Light is usually applied to the painful area and is thought to cause temporary inhibition of axonal transport in small diameter nerve fibers (A⁢𝛿 and C)." [30]

The quotes above explains this inhibition is reversible and works on mechanisms that do not cause damage. Meaning the nerve integrity is still in tact, it just temporarily blocks nerve transduction (signaling).

Timeframe of Nerve Inhibition:

As usual, the effects of Photobiomodulation occur minutes after the treatment has ended, peaks over a few hours, then returns to baseline in about 24 hours. The effects of overdosing red light therapy is likely temporary and washes out after 1-2 days. 

One article measured the nerve firing was reduced 5 minutes after receiving the laser treatment. The inhibition lasted for 3 hours. [29]

"LLLT has been shown to inhibit action potentials in peripheral nerves equating to a 30% neural blockade within 10 to 20 min of application, which is reversed within 24 h []. " [31]

Another article used relatively high doses on rodent brains to reduce pain sensations. The peak reduction in pain occurs 2-3 hours after the PBM treatment. At about 24 hours later the effectiveness subsides. 

"The assessment of pain threshold in mice demonstrated that photoneuroinhibition of pain was a temporary and reversible process, with a peak between 2 and 3 h and finished by 24 h after transcranial laser irradiation." [30]

This article also showed pain reduction peaked 2-3 hours post PBM treatment. 

"NIR (810 nm) laser irradiation to the lower back of mice reversibly increased the pain threshold in the hind paw up to threefold, with a peak at 2–3 hours post-PBM. A dose response was observed, with 6 and 30 J/cm2 being effective and 1.2 J/cm2 being ineffective." [32]

This is why occasionally "overdosing" red light therapy does not generally lead to any permanent damage. The inhibitory effects are often short-lasting and reversible. An overdose could be followed by abstinence from red light therapy for a period of time so the effects fade to return to baseline. 

Biphasic Response to the Biphasic Response:

The adage of "more is not better" rings true with Red Light Therapy dosing. As we increase the dose, the biological effects cross the threshold from stimulatory to inhibitory. 

However, one new human study found there is also an optimal dose to achieving the proper inhibitory response. Naturally we would assume that once we are in the inhibitory region, more dose would simply cause more inhibition. But this is not the case. 

A 600mW 810nm laser was used to inhibit dental pain. They compared 2 different doses to the conventional anesthesia spray. They applied the 600mW laser for 40 seconds to one group and for 180 seconds (3 minutes) for another group. The 40 second treatment time performed better than the 180 second treatment time and the spray. [57]

Thus, they found the dose of 48 J/cm^2 performed better than the dose of 216 J/cm^2.[57]

Even with inhibitory dosing, there is some optimal window or goldilocks' dosing zone for achieving the proper effects. Which of course would imply the dose-response effects are not a simple biphasic response but multi-phasic with many different effects. Especially as the doses and intensities extend beyond the normal scope of Photobiomodulation parameters, only within the conventional window of parameters of PBM that the effects appear to be mostly biphasic. 

High Fluence for Psoriasis and Atopic Dermatitis 

Psoriasis and Atopic Dermatitis (eczema) are inflammatory skin conditions. Recent research shows the root cause is overactive immune T cells. [33] As such, modulating or inhibiting the overactive skin cells with light is a viable treatment avenue. [34]

Phototherapy is already conventionally employed as treatment for both of these conditions. They typically use Ultraviolet (UV) light. [35][36]  Ultraviolet is ideal for its superficial application and being efficient at causing an inhibitory effect.  

However, some early indications show that high dose Red Light Therapy could also serve the same purpose. 

One study used 633nm wavelength at 3.0 J/cm^2 and had 40% of the patients have an improvement in psoriasis. [37]

However, an earlier study used 830nm at 60 J/cm^2 and 633nm at 126 J/cm^2 for a larger improvement in their group. [38] Perhaps the higher dose was the reason for the higher effectiveness to inhibit the immune cell activity and skin cell turnover. 

High Fluence Light Therapy on Cancer:

High Dose Red Light Therapy has also been proposed to inhibit cancer cells and arrest tumor growth.

Note that these are typically on isolated cells or small animals, and should not be attempted at home without a doctor's approval or supervision. 

"When this high dose is used, light inactivates Cox (instead of activating Cox), inducing a superoxide burst in the electron transport chain and, finally, produces oxidative damage against cancer cells []" [39]

The above quote notes that overdosing red light therapy inactivates Cytochrome C Oxidase (Cox), which they highlight is the opposite effect of low dose red light therapy. 

One study used 256 J/cm^2 to inhibit cell viability of colorectal cancer cells. [40]

Another study used 160 J/cm^2 with a 633nm laser to inhibit liver carcinoma cells, and confirmed the apoptotic pathway was initiated by ROS. [41]

A study from the same group used 120 J/cm^2 with a 633nm laser to inhibit lung adenocarcinoma cells. [42]

A 2019 study used up to 40 J/cm^2 from different laser wavelengths 636nm, 825nm, and 1060nm on breast cancer cells. [43]

"in this project we investigated the possible bioinhibitory effect that treatment with high fluences of 20 and 40 J/cm2"[43]

However, they found that the doses used were ineffective or caused proliferation of the cancer. 

"The use of LILI alone with the aim to eradicate cancer cells has still not yield convincing results"[43]

Using red light therapy on cancer cells is still controversial due to the biphasic nature of the treatment. However, this section was just to expand the point that higher doses are expected to have inhibitory responses on cells, and discuss some of the mechanisms they found. 

Mechanisms of High Fluence Red Light Therapy

Here are some of the reported mechanisms that causes cellular inhibition or initiates apoptosis from overdosing red light therapy.

  • Triggers mitochondrial oxidative stress [44]
  • High ROS production inhibits functions or triggers apoptosis [45] 
  • High Nitric Oxide will block cellular functions [26] 
  • Accelerates Calcium (Ca+) uptake into the cells [46]
  • Initiates a burst of superoxide anion radical O2− [47]
  • Triggers the caspase-3 pathway for apoptosis [48]
  • Induces the Mitochondrial permeability transition (mPT) for apoptosis or necrosis [49]
  • Activates glycogen synthase kinase 3β (GSK3β) for an apoptotic pathway [50]

Safety in Low Intensity with High Fluence

One article exposed pancreas cells and rodents to 2.8mW/cm^2 for up to 24 hours of continuous exposure time. For a maximum dose of 241.9 J/cm^2 at 24 hours of exposure. They note that there was no toxic effects, in contrast to previous studies that used higher intensities to achieve a similar dose. [51]

The authors explain that under long-term light stimulus the cells may respond by finding a new equilibrium for normal functioning. [51]

Similar to how long-term low-intensity exposure to indoor Red/NIR lighting (incandescent bulbs) or sunlight is often not given much attribution of Photobiomodulation effects. As we would also be concerned of inhibitory effects from long term exposures of ambient lighting. Perhaps during long exposure times the cells adapt to return to a new normal function, as indicated by this study. 

High Dose Safety for Brain Treatments

A recent May 2025 article reports on a study conducted on 31 humans to assess the safety of 3 different doses on the brain through the head (transcranial Photobiomodulation, tPBM). Each participant got a single treatment of each dose, and were monitored for potential side effects. [53] The 3 doses (and 1 sham treatment) were spaced 1 week apart. 

They used an 808nm laser with doses of 60, 100, and 180 J/cm^2. [53] The participants were surveyed for a long list of potential side effects. Overall there were no statistically significant side effects reported.[53] 

The authors noted that 6-10% of the participants report "delayed or absent orgasm" as a side effect. The High dose treatment had 13.3% of participants report tinnitus (ringing in the ears or trouble hearing) as a side effect. [53]  Although 10% of the participants reported tinnitus after the sham (placebo) treatment too. The authors recommend that these types of side effects should be monitored with larger studies with more people in the future. 

Other interesting side effects but only reported by 1 to 3 participants out of 31:

  • "Apathy/emotional Indifference"
  • "Weakness or Fatigue"
  • "Stuffy Nose"
  • "Clenching of teeth at night"
  • "Nightmares or other sleep disturbance"
  • "Diminished mental acuity/sharpness"
  • "Heartbeat rapid or pounding"

The participants were also evaluated for biomarkers relating to depression, but with a single dose there was no significant improvement. [54]

A single high dose (technically 3 high doses in 4 weeks) with reasonable range of parameters does not show any significant or concerning side effects on the brain, nor does it show significant improvement. This does establish a good margin of safety for future studies to build from. 

They comment that typical side effects from previous studies on the brain are minor and include transient headaches, insomnia, irritability, visual disturbances, strange mouth taste, and abdominal bloating. [53]

High Intensity + High Dose + Heat?

One study on rodent testicles applied 200mW/cm^2 for 30 minutes with either 670nm or 808nm wavelength lasers. For a dose of 360 J/cm^2 for 5 consecutive days.

They found atrophy of the testis cells from the 808nm laser, likely due to the deeper penetration. The 670nm showed no damage to testicles, likely because more of the energy was absorbed by the superficially by the skin thus protecting the organ. 

We can easily see multiple layers of problems with this study design:

  • Very high intensity
  • Very long exposure time
  • Very high fluence
  • Repeated exposures on consecutive days

If one or more of these parameters was drastically reduced, they likely could have avoided such significant problems. 

There was no mention of monitoring tissue temperature during treatment. That may have also played a big role in these results. 

This article was published in 2013. The authors discuss that through this experiment they have learned about the Biphasic Dose Response the hard way. 

"That is, laser irradiation of higher doses is associated with the growth inhibition and cell lethality [11]. A biphasic dose response has been frequently observed where laser irradiation of lower doses have a much better effect in stimulating and repairing tissue as compared with that of  higher doses [16]." [52]

In the year 2025, we hope that consumers do not have to learn about the Biphasic Dose Response the hard way. 

Conclusions:

High Fluence Low Power Light Therapy is a promising area of research. The advantage is delivering high energy density (J/cm^2) that inhibit specific cells while minimizing risks of cellular damage, phototoxicity, or overheating. 

However, the downside is the low power requires very long exposure times, often over 30 minutes or even on the scale of hours. 

This is why it rare to inadvertently overdose Red Light Therapy. Using reasonable intensity ranges 5 to 50 mW/cm^2 and appropriate exposure times 1 to 20 minutes would avoid overdosing to the inhibitory range. 

To illicit cellular inhibition or apoptosis, other types of light therapies are often used. For example:

  • Wavelengths like UV, Blue, 750nm, and 950nm will cause cellular inhibition or apoptosis at much lower doses. 
  • Photodynamic Therapy (PDT) combines photosensitizers and light therapy for an inhibitory response.
  • High Intensity light therapy can produce inhibitory responses not only quicker but with lower doses, often when combined with heat. 

These methods are already much more prominent for the same applications we discussed in this blog for High Fluence low power light therapy. Thus, we we don't see many articles using High Fluence Low Power when these other techniques are being explored as faster, more consistent options. 

However, researching high fluence red light therapy gives us new insights into the relative safety of overdosing red light therapy. 

 

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