Mitochondrial dysfunction - a decline in mitochondrial quality and activity, has been associated with normal aging and correlated with the development of a wide range of age-related diseases, including infertility.
Introduction
You might remember from your high school biology class that every cell in the body has specialized structures (organelles) called mitochondria. These organelles are responsible for the production of Adenosine Triphosphate (ATP) - the primary energy unit in our bodies. When a cell has plenty of ATP it can carry on with its specialized function, repair itself (against cancer, viruses, etc.), and perfectly replicate itself (without chromosome abnormalities). Unfortunately, as we age, the mitochondria begin to slow down and the cells have a harder time repairing themselves and replicating themselves without mistakes…i.e. aging.
Several studies have shown that mitochondria influence or regulate a number of key aspects of aging. And because of this, scientists have been trying to come up with different strategies to improve mitochondrial quality and function. For example, by understanding that ATP is generated directly by the mitochondria through a process known as the electron transport chain (see blog about CoQ10), which depends mainly on CoQ10 and NAD+, health practitioners are now recommending these two supplements to heal different health conditions.
Another strategy that is becoming very popular and attracting the attention of many health practitioners is red light therapy. Red light therapy is a natural treatment that uses specific wavelengths of visible and invisible light to stimulate the production of ATP inside the mitochondria. Unlike natural sun therapy, red light therapy does not contain UV light so it’s safe for the skin.
Red Light Therapy
Light therapy has been around since 1967 when a Hungarian physician by the name of Endre Mester developed the first low-level laser therapy device. He first tested its effects on skin cancer, and later on wound healing. As technology advanced, allowing LED light bulbs to be more efficient and cheaper to produce, LEDs became very popular with light therapy. While not as targeted or strong as a laser, LEDs still give off consistent color of light, making them great for light therapy.
Under the umbrella of Photobiomodulation, the technical name for light therapy, there are a few technologies and terms that are worth reviewing:
Low-level light therapy or low-level laser therapy (LLLT). These are high-powered lasers that are usually used surgically to kill certain cells or remove tissue. They are also used in dermatology clinics to improve skin complexion and reduce signs of aging. They can deliver red and near infrared light.
LED light therapy refers to light treatment using light-emitting diode (LED) devices as opposed to lasers. LEDs are very safe since they generate very little heat and there’s no danger of burns. Medical-grade LED devices can deliver professional results.
Infrared Therapy could refer to either near-infrared (wavelengths from 810 to 850nm) or far-infrared (wavelengths over 1,000nm). Unlike far-infrared light (like those found in infrared saunas) which generates heat, near-infrared light, like red light, does not generate heat.
Visible red wavelengths (620-650nm) treat each layer of skin tissue, helping with health issues such as arthritic joints, over-trained muscles, and inflammatory skin conditions. Near-infrared wavelengths (810-850) penetrate significantly deeper into the skin, helping with deeper tissues.
How photobiomodulation works
At the end of the electron transport chain there is an enzyme known as Cytochrome C Oxidase (CcO), which is the primary site of cellular oxygen consumption. It is here where the oxygen atom needs to attach to finish the last step of ATP production and generate energy. Unfortunately, due to diet and lifestyle, there can be more free radicals inside the cell than oxygen. One of these free radical molecules is nitric oxide (NO). This molecule, having an unpaired electron on its outer layer, has a higher affinity for the CcO enzyme than oxygen so it attaches there first. Once NO is attached to this enzyme, oxygen cannot attach and the ATP process cannot be completed. Photobiomodulation unbinds NO from the CcO enzyme allowing an oxygen atom to bind to the enzyme and complete the ATP process. The now free and unstable (high affinity to attach to other molecules) NO can bind to other molecules in the body. For example, by binding to soluble guanylate cyclase (sGC), NO produces a vasodilator effect. This can increase regional blood flow to an area of interest, such as the ovaries, the testes, or even the penis in case of erectile dysfunction.
Amongst the many studies and research papers on the topic of red light therapy and its benefits on mitochondria, they all seem to agree that photobiomodulation can free up the CcO enzyme from NO, allowing for oxygen to occupy that site. A review published in 2014 by Lasers in Medical Science, a peer-reviewed medical journal covering laser medicine, explains that:
“ Light can indeed reverse the inhibition caused by NO binding to cytochrome oxidase, both in isolated mitochondria and in whole cells.”
At the cellular level red and infrared light therapy can dissociate NO from CcO, which disinhibits the enzyme and allows it to better utilize oxygen, participate in the electron transfer chain, and create ATP.
As reported by many studies, near infrared light (NIR) enhances the activity of mitochondria by increasing cytochrome c oxidase activity. The reason for this is that cytochrome c oxidase contains several chromophores (molecule which absorbs light at a particular wavelength), including two copper centers that are involved in enzyme catalysis (copper broadly absorbs NIR in the range of 700–1000 nm). When light in the range of NIR hits the cytochrome c oxidase enzyme, it unbinds it from the other molecules making the site available for oxygen once again.
Mitochondrial Quality and Fertility
ATP production is extremely important for highly metabolically active cells such as sperm and egg cells. Most human cells have around 2,000 mitochondria, but human egg cells have as many as 600,000. By making sure that the mitochondria in a human egg are working at their full potential, the quality of that egg is improved. According to a study published by The Journal of Assisted Reproduction and Genetics, women with mitochondrial DNA mutations have a lower implantation rate and a higher aneuploidy rate (any number of chromosomes other than the usual 46). In addition, since mitochondria are inherited from mother to child, it is important that oocyte mitochondria be intact.
A scientific review published by Current Opinion in Obstetrics and Gynecology, summarized their findings by saying that:
“ Optimal energy production is required for oocyte and embryo development, and mitochondrial abnormalities have devastating reproductive consequences”
A study conducted in Denmark where 239 women between the ages of 34 and 50 were treated for infertility using photobiomodulation reported having a 66% success with 159 pregnancies – including one woman of 50 years old!
An animal study published in 2017 by Lasers in Medical Science where red light (RL), near infrared light (NIRL) and Clomiphene (Clomid) – a drug used in fertility clinics to stimulate egg (oocyte) growth, were compared to see which provided the best folliculogenesis cycle (egg maturation). While NIRL and RL proved to produce better or same folliculogenesis than Clomid, the increase was significantly better with NIRL. The study concluded that: “This indicates that NIRL increases ovarian activity to produce oocyte that certainly can be used in future studies for finding a cure to ovarian negligence to produce more oocyte and treat diseases caused by it like PCOS”.
Laser Therapy, a journal for laser surgery, phototherapy, and photobioactivation, published in 2012 a Japanese study titled “Personal Overview of the Application of LLLT in Severely Infertile Japanese Females”. The study, which included 701 severely infertile females and lasted from 1996 until 2012, concluded that: “The use of 830 nm LLLT in the proximal priority technique at the parameters used in the present study, on its own or as an adjunct to other techniques, resulted in successful induction of pregnancy in just over 21% of severely infertile females”.
Other Benefits
Since the benefits of photobiomodulation are directly linked to the improvement of mitochondrial quality and activity, the benefits of RL and NIRL are many. From pain management to better skin, to hair growth and nail fungal infection, light therapy offers many applications. For example, temporomandibular pain, or TMJ, has been shown to improve after 4 weeks of treatment of near infrared light. Reduced pain after orthodontic treatment has been shown during near-infrared treatments. A study published in 2021 by the International Journal of Medical Sciences titled “Near Infrared (NIR) light therapy of eye disease” concluded that: “Therefore, NIR light is significant for applications to eye and neuron therapies to retinal damage by correction of mitochondrial disorders”.
An additional benefit of photobiomodulation, and a very important one for fertility, is stress reduction. Due to the natural production of endorphins as one of the many biological responses of photobiomodulation, stress level can be reduced significantly.
Acupuncture and Photobiomodulation
While light therapy is usually done by itself, adding a few acupuncture needles can enhance the treatment, although there is not a lot of literature showing the benefits of acupuncture when combined with light therapy. In the case of facial acupuncture, however, there is an article showing benefits when combining these two therapies, and there are a few studies showing the positive effect of applying infrared light directly on acupuncture points.
The Treatment
By following the Japanese and Danish studies, the best protocol seems to be two to three treatments per week (depending on age) during the follicular phase of a woman, and one to two times in the post-ovulation phase to assist egg quality and uterine lining production. If conception does not take place, then the protocol is repeated the following month. Acupuncture is used to support implantation and to continue to support developing follicles in the ovaries.
Conclusion
Red Light Therapy has been shown to offer many benefits: from relieving aches and pains to improving skin quality through collagen production to helping ease side effects of traumatic brain injuries. In the past few years red light therapy has entered the world of fertility with a very promising outlook. Since photobiomodulation is based on increasing the quality and activity of mitochondria, its application is almost endless.
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