Right light therapy is said to target cytochrome C oxidase, complex IV, of the mitochondria. Most complexes of the mitochondria contain functional groups that absorb one wavelength of visible light or another. Absorption of light may translate into increased membrane potential, which translates into more ATP. This post introduces the role of ATP in the cross-bridge cycle of skeletal muscle. Is there a scientific basis for increased ATP production and less muscle cramping?
Light and heme Fe in mitochondria[1]
A previous post examined nitrosothiol and nitric oxide bound heme iron regulation of guanylyl cyclase. Cytochrome C oxidase of the mitochondria has two heme groups that can bind to nitric oxide. This binding can explain some of red light therapy. We have known about the influence of 660 nm red light with a power density of 10 mW/cm’ at room temperature on isolated rat liver mitochondria. [1]
Deciphering electron transport chain complexes
Electrons may enter the electron transport chain by two means: NADH and succinate, both products of the Tri Carboxylic Acid cycle. ATP synthase, also known as complex V, is not really part of the electron transport chain. This cartoon is a Wikimedia Commons image of the electron transport chain. Fig 1 of Yu 2023 [1] pretty much said the same thing. The coupling site I1 of the electron respiratory chain, which is located on the path of electrons from cytochrome b to cytochrome c, was evaluated using succinate as an electron donor and using rotenone to block between NADH and CoQ path.
Data in table 3 were generated with commercial colorimetric kits. An oxygen electode was used to generate data in Table 1.
Succinate and ascorbate are ways of introducing electrons other than NADH. Complex V and lactate dehydrogenase activities were not effected by 660 nm red light.
The Phosphate Potential refers to the concentration of ATP (adenosine triphosphate) in a system divided by the product of the concentrations of ADP (adenosine diphosphate) and inorganic phosphate. This is in very simple terms. One takes a natural log of this number and does some other things that are beyond the scope of this post. Both phosphate potential and energy charge reflect the energy state of the isolated mitochondria. After a 7 min incubation, but not 12 min, both the phosphate potential and energy charge were significantly increased.
Slide share is a good source of some of these electron transport complexes showing light absorbing F-S centers and heme groups. The following list compares results of Yu 1997 with the functional groups according to a slide show taken from Lehninger .
- Complex I NADH-Q reductase (slide 17-19), Fe-S centers, 660nm at 1.2 J/cm2 and 2.4 J/ccm2increased activity
- Complex II succinate dehydrogenase, (slide 20) FAD and an fe-S center. red light had no effect
- Complex III cytochrome C reductase (slide 22) a heme group and an Fe-S center. All intensities tested increased the activity, sometimes up to about five fold.
- Complex IV cytochrome C oxidase (slide 25) two heme groups and two coppers. All intensities tested increased activity almost two fold.
Yu and coauthors seem to be proposing the same model as proposed in the light and guanylyl cyclase post. What happens when light is absorbed by a biological molecule? The electronically excited state decays to a vibrationally excited state. This vibration might facilitate the transfer of a proton out of the matrix. Oxidative metabolism seems to refer to the ATP synthesis coupled transport of the H+ back into the matrix of the mitochondria. The oxidative part is of course oxidation of NADH, succinate, or ascorbate in a manner that necessitates that coming together of the complexes. Does vibration that occurs with photon absorption and subsequent decay facilitate this process?
Red vs other colors [2]
This study out of Bologna used an Italian “flash light” type device to irradiate cultured fibroblasts at subsequent measurement of the mitochondrial membrane potential with Mito Tracker. See Fig 2.
| Wavelength (nm) | Color | Nominal peak power (mW) | Used LED (data sheets available on request) | Current value for a irradiance of 0.1 mW/cm2 (mA) | Membrane potential |
|---|---|---|---|---|---|
| 440 | blue | 19–23 mW | LLS-UV400 | 3.65 | no change |
| 525 | green | 100 cd | G58A5111P | 4 | <2x at 24 hr |
| 645 | Red | 11 mW | LED-645-03 | 5.90 | >2x @ 24 & 48 |
| 660 | Red | 15 mW | LED-660N-03 | 10 | no change |
| 780 | FR/IR | 45 mW | ELD-780-525 | 11 | 2x @ 24 hr |
| 900 | IR | 48 mW/sr | B5B-900-8 | 26 | no change |
Cells were exposed for short intervals a t24, 48, and 72 hours. The membrane potential was measured with MitoTracker. Green light of 525 nm and red light of 645 and 780 nm resulted in several fold increases in membrane potential at 24 hours. Mitofuscin, a mediator of mitochondria fusion, was increased by 645 nm light but not by 900 nm light.
This post will not go too deeply into this study, but we should not that there are lightly to be multiple light absorbing functional groups in the electron transport chain complexes.
ATP production in mouse soleus and gastrocnemius [3]
“Recently, low-level laser (light) therapy has been used to increase muscle performance in intense exercises. However, there is a lack of understanding of the time response of muscles to light therapy.
- The first purpose of this study was to determine the time response for light-emitting diode therapy (LEDT)-mediated increase in adenosine triphosphate (ATP) in the soleus and gastrocnemius muscles in mice. Each subgroup was analyzed for muscle ATP content or fatigue at specified time after LEDT.
- Second purpose was to test whether LEDT can increase the resistance of muscles to fatigue during intense exercise. Fifty male Balb/c mice were randomly allocated into two equal groups: LEDT-ATP and LEDT-fatigue. The fatigue test was performed by mice repeatedly climbing an inclined ladder bearing a load of 150 % of body weight until exhaustion.
LEDT used a cluster of LEDs with 20 red (630 ± 10 nm, 25 mW) and 20 infrared (850 ± 20 nm, 50 mW) delivering 80 mW/cm2 for 90 s (7.2 J/cm(2)) applied to legs, gluteus, and lower back muscles.
Both groups were subdivided into five equal subgroups:
- LEDT-sham,
- LEDT-5 min,
- LEDT-3 h,
- LEDT-6 h LEDT-6 h was the subgroup with the highest ATP content in soleus and gastrocnemius compared to all subgroups (P < 0.001). In addition, mice in LEDT-6 h group performed more repetitions in the fatigue test (P < 0.001) compared to all subgroups
- LEDT-24 h. “
A high correlation between the fatigue test repetitions and the ATP content in soleus (r = 0.84) and gastrocnemius (r = 0.94) muscles was observed. The closer the correlation coefficient is to 100, the more confident we are that the tow are correlated. It should be remembered that the gastrocnemius and soleus are the two calf muscles in human. These two muscle groups tend to cramp in an enigmatic condition called night cramps.
This is why increasing ATP production by the mitochondria can reduce muscle fatigue. Central to this argument is that it may also reduce muscle cramping by those nasty “rigor” cross-bridges.
References
- Yu W, Naim JO, McGowan M, Ippolito K, Lanzafame RJ. (1997) Photomodulation of oxidative metabolism and electron chain enzymes in rat liver mitochondria. Photochem Photobiol. 1997 Dec;66(6):866-71 Sci-Hub free paper
- Baldassarro VA, Alastra G, Lorenzini L, Giardino L, Calzà L. Photobiomodulation at Defined Wavelengths Regulates Mitochondrial Membrane Potential and Redox Balance in Skin Fibroblasts. Oxid Med Cell Longev. 2023 Aug 24;2023:7638223. PMC free article
- 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. PubMed
Red Light Therapy Home on mitochondria and night cramps
Do you experience nocturnal cramping of your soleus and gastrocnemius or other leg muscles? The causes are many. Interestingly, magnesium is one of the few effective treatments. Magnesium stabilizes the high energy phosphate in ATP that is essential for release of rigor cross-bridges. Dehydration is another issue that can compromise blood flow and hence generation of ATP, which of course requires oxygen, see the featured image. With these things said, how might a person suffering from night cramps use red light? Do they use it for six hours as per the Ferraresi mouse study, or do they build a tent to irradiate their legs as they fall asleep to aid in blood flow and ATP production so their muscles do not start cramping?
Best Practices for Using Red Light Therapy for Mitochondrial Health
You can effectively use red light therapy and obtain good results if you carry out the process intelligently. In order to enhance mitochondrial activity, employ a machine that radiates particular wavelengths and keeps a distance of 6-12 inches between the machine and the target area. Using this process with a good tool such as the Total Spectrum device 3-5 times per week would be adequate, and the session should be 10-20 minutes for improved outcomes. In addition, you should read the directions in our detailed instructions that come with your device in order to use this treatment appropriately.
If you would like to order your own red light therapy device from Red Light Therapy Home, use this promo code for a 6% discount
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