Some publications have been written about the therapeutic potential of osmolytes for diverse diseases, among which cancer and neurodegenerative diseases like Alzheimer's.
Osmolytes are considered to be protective molecules that organisms can accumulate during periods of stress, especially when water consumption is not possible.
The uptake of osmolytes by cells is known to be controlled by a transcription factor called NFAT5 (or TonEBP) in the literature. NFAT5 is also associated with a number of diseases: auto-immune and cardiovascular ones, diabetes and cancer.
When mammalian cells are osmotically stressed, this transcription factor allows the expression of genes that code for proteins (“transporters”) involved in the transport of osmolytes inside them:
Functionally, NFAT5 activates a large number of target genes implicated in osmoprotective responses, including those encoding aldose reductase, the betaine transporter, and the inositol transporter [113]. With its wide range of cell type and tissue expression patterns, NFAT5 plays a prominent role in restoring intracellular osmotic balance under hypertonic conditions.
Inside cells, osmolytes allow to counter osmotic stress without disturbing the normal processes. It is also thought that they allow for the proper folding of proteins (in their 3D structure or “conformation”) and also have an effect on the properties, in particular the structure, of the water they are concentrated into:
All selected stabilizing osmolytes enhance water structure in their surroundings, which promotes tighter protein folding in aqueous systems.
Also, it has been proposed in the literature that the state of intracellular water (i.e. structured or un-structured), is a driver of the cell’s health state:
Interestingly, aging cells show an increase in intracellular water volume, but this fact is barely explored in aging studies. All cells have a crowded cytoplasm, where the high concentration and proximity of macromolecules create an environment that excludes many small molecules, including water. In this crowded environment, water can be found in two states termed low density water (LDW), which shows low reactivity and has an ice-like structure, and high density water (HDW) that has a disorganized structure and is highly reactive. LDW predominates in a macromolecular crowded environment, while HDW is found only in microenvironments within cytoplasm. In this sense, we hypothesized that the failure in the water homeostasis mechanisms with time changes the equilibrium between LDW and HDW, increasing the concentration of intracellular HDW. Being reactive, HDW leads to the generation of reactive oxygen species and disturbs the crowded cytoplasm environment, resulting in a diminished efficiency of metabolic reactions. Noteworthy, the cell becomes less prone to repair damage when the concentration of HDW increases with time, resulting in aging and finally death. Interestingly, some biological mechanisms (e.g., anhydrobiosis) reduce the concentration of intracellular water and prolong the life of cells and/or organisms. In this sense, anhydrobiosis and related biological mechanisms could be used as a platform to study new anti-aging therapies.
Aging as a consequence of intracellular water volume and density
This publication makes the hypothesis that during aging (and diseases), the intracellular water loses its structure which impairs the metabolic efficiency and the cell's repair mechanisms.
It is also noted in the end of this excerpt that, anhydrobiosis (which means “life without water”) and designates life forms that are able to withstand important levels of dehydration without dying, and which is, from what is known, made possible thanks to osmolytes, could be studied to help fight against aging.
Another publication proposes that in addition to provide osmolytes, being in a state of hyperosmolarity (“dehydration”) could be helpful as it would have for effect to flush the unstructured water and stimulate the uptake of osmolytes. This could thus help restore the normal metabolism of cancer cells:
The decrease in the cytoplasmic kosmotropic osmolytes gradually transforms the structured water into unstructured water, which eventually causes a reduction in the order-information degree of the cellular thermodynamic-energy system, which upon reaching the maximum tolerable entropy, causes the cell a “near-death state”. […]
Measures that transform unstructured water into structured water, such as peritumoral hyperosmolality and increased intracellular kosmotropic osmolytes, and strategies that increase mitochondrial oxidative phosphorylation may restore physiological and cellular bioenergetics. […]
Research efforts have suggested that the promotion of hyperosmolarity can be used as a form of treatment.
Hyperosmolarity increases EZ (structured) water inside the cell, which in turn promotes apoptosis.
Structured Water and Cancer: Orthomolecular Hydration Therapy
TLDR:
Osmolytes are substances that could help cells structure their intracellular water and restore their proper oxidative metabolism.
Flushing unstructured water from cells with help of hyperosmolarity (e.g. by drinking less water) might help this process.
Very interesting. I once looked at mannitol which was claimed to be helpful in Parkinson's - I discovered it was an osymolyte and this may be the why it works to help clean up the brains of people with Parkinson's https://www.outthinkingparkinsons.com/articles/mannitol