Methylene blue is a photosensitizer that is used extensively in medicine particularly to distinguish between malignant and healthy cells. A photosensitizer absorbs light, which results in a photochemical change within the molecule. When light strikes a solid object, it can either be scattered or absorbed. According to photochemistry, absorbance is necessary for photochemical changes to happen. Compounds that exhibit absorbance are called chromophores. The absorbed light leads to an energy exchange in which the molecule can release heat and/or fluorescence.
Methylene blue is a phenothiazine dye and is the only molecule in this class to be extensively evaluated for clinical applications. It is effective at marking tumors both for diagnosis and surgery. Currently, methylene blue is being tested at reducing pathogens in blood products. The Red Cross is using methylene blue to reduce bacterial contamination in blood products and for eliminating plaque.
More research is investigating additional uses of methylene blue and its derivatives, including treatment for chronic skin tumors. The compound has been in use for over a century and is used as a treatment for diseases including methemoglobinemia, malaria, vasoplegia, septic shock, cancer chemotherapy, and Alzheimer’s disease.
Methylene blue as an antioxidant
Aging cells cannot fight against free radicals due to a decrease in the skin’s normal arsenal of antioxidants. While this varies between individuals, the depletion still impacts the need for antioxidants especially due to environmental pollutants that negatively affect the skin.
Antioxidants are essential at all ages to maintain healthy skin: researchers in both dermatology and cosmetic science are pinpointing many free radical-induced skin disorders. Methylene blue is a unique antioxidant that targets reactive oxygen species (ROS) and induces permanent changes in cellular aging. A unique feature of methylene blue is the ability to make permanent changes within the cell by keeping ROS at low levels in all three of the major skin layers. This reverses cell senescence.
In addition, fibroblasts showed a significant increase in cell division leading to increased skin thickness in elderly patients along with an increase in hydration to levels associated with younger skin. Other studies found a reduction of both beta-galactosidase and the P16 gene, which are indicators of cell senescence and aging. Further simulations have confirmed these results.
Using methylene blue to protect the mitochondria
The penetration and cellular uptake of methylene blue make this compound special. The antioxidant properties of methylene blue have been known since its discovery in 1876. As scientists have studied this compound, they have learned a lot about the role of uncontrolled ROS and their effects on skin health and disease. Thus, more attention has been given to antioxidants in recent years for prevention and cure.
The mitochondria provide energy by converting carbohydrates into adenosine triphosphate (ATP), which cycles and recycles the converted energy to cells by means of the electron transport chain. In this process, ROS are formed through cellular metabolic waste
As a result, the regulation of ROS within the mitochondria is most efficient through the electron transport chain containing an antioxidant, which can move freely in and out of the mitochondrial membranes.
Methylene blue penetrates mitochondria and modulates ROS
Penetration into intercellular compartments of the mitochondrion and lipid membranes reflects methylene blue’s amphipathic properties (it is both oil and water-soluble). It is compatible with many solvents and has a low redox potential of 11mV. Most antioxidants are either predominantly oil or water-soluble. The amphipathic feature of methylene blue enables it to move in and out of mitochondria giving it the ability to regulate the accumulation of ROS in mitochondrial membranes and mitigate senescence and premature aging of the skin.
These properties of methylene blue translate into a self-generating antioxidant that can exist both in its oxidized and reduced forms simultaneously. The ability to accept electrons in the oxidized state or reject elections in the reduced state allows it to enter the electron transport chain and mitigate free radical buildup. This directly impacts cell functioning and can reverse the aging process.
Studies have found that this property at relatively low methylene blue concentrations (0.5 to 2.5 µM) is effective. At this low concentration, there is no blue staining of cells. However, repeated use could lead to cumulative effects on the skin which should be addressed in pre-clinical/clinical studies.
Anti-aging benefits of methylene blue
Aging skin becomes thin, dry, and wrinkled and has reduced water retention. Tissue staining studies have shown that treatment of skin with methylene blue (0.5 µM) results in increased thickness of the dermis as well as elevated skin hydration. It should be noted that several studies used simulation models, so results may not be easily reproduced. Even so, the ability to improve the hydration of aged skin has perceivable benefits like a healthier glow, wrinkle reduction, and smoothness.
Aging skin also loses collagen and elastin, which impact skin thickness. This occurs because of decreased enzyme production and increased ROS in the dermis, which results in a degenerative cycle increasing the aging process. After the age of forty, production of both elastin and collagen falls off rapidly while the ROS accumulates, adding to the degenerative cycle.
Increased levels of ROS are a prime cause of both skin aging and disorders as the buildup directly results in both the breakdown and production of collagen and elastin. Elastin is an extremely important dermal protein that maintains skin resilience, pliability, and elasticity. The harmful effects of low levels of collagen and elastin show up as sagging, wrinkled skin.
These effects may be avoided using an antioxidant such as methylene blue. Researchers conducting skin tissue work demonstrated an increase in elastin fibers within the dermis after two weeks of treatment with methylene blue. The participants were able to see the benefits directly.
These unique properties of methylene blue mean that it may fill a key role in antioxidant skin products. Along with both water and oil soluble vitamins and polyphenols, dermatology and cosmetic science now have an additional product.