Multiple sclerosis has been the subject of numerous studies that have tried to figure out ways to fight and prevent the disease. One recent finding could be the key to discovering more about multiple sclerosis, and it has to do with the disease's waste disposal.
Waste Disposal Explained
Like most organisms, cells in the body produce waste that they have to get rid of. They remove waste in a process called autophagy or "self-eating". In this process, waste products are surrounded by an inner folding cell of the membrane which forms a vacuole (space in the cytoplasm of a cell containing liquid). This vacuole fuses with a lysosome (a specialized vacuole packed with digestive enzymes) to safely dispose of the waste and release the products into the body for recycling purposes.
Autophagy as a process has only recently been discovered, and it was deemed so groundbreaking that it won Yoshinori Ohsumi the Nobel Prize of 2016. Neurons in particular have been showed to be incredibly dependent on autophagy. This is because they often have far projections (also called dendrites and axons) that do not divide and are metabolically active. This all leads to a high requirement for autophagy to occur in most neurons. Autophagy is so important that dysregulation of autophagy is present in many neurodegenerative diseases like Parkinson's disease and even normative aging. This finding of dysregulation in Parkinson's made researchers question if waste disposal is dysregulated in multiple sclerosis, another neurodegenerative disease.
One study conducted by Patergnani et al. Attempted to find out how waste disposal was affected when multiple sclerosis is present in the body. They took blood and cerebral spinal fluid sample from 40 patients who had relapsing-remitting multiple sclerosis (RRMS), 40 people with other inflammatory central nervous system diseases, 40 people with non-inflammatory central nervous system diseases, and 20 healthy control patients. They measured a biological marker of autophagy (ATG5) to see if autophagy was increased or decreased in MS patients.
Researchers found increased levels of ATG5 in both the blood samples and cerebral spinal fluid of multiple sclerosis patients. This seems to imply that autophagy occurs more than usual in multiple sclerosis cells. ATG5 was also linked to TNFalpha, an inflammatory cytokine within the cerebral spinal fluid that is linked to central nervous system inflammation. This may mean that increased autophagy could be a sign of inflammation of the central nervous system, one of the symptoms of multiple sclerosis.
The biggest question for researchers after this finding is how this upregulation of waste disposal actually affects multiple sclerosis patients. Is the autophagy protective or harmful? How does it relate to the progression of disease? These questions and more must be answered before researchers know the effects of autophagy well enough for them to be of use. It should be noted that one tangentially related study may imply that autophagy is actually beneficial. That study and its implications will be discussed below.
Fasting Mimicking Diets and Multiple Sclerosis
Dietary interventions have previously proven to be very ineffective in treating multiple sclerosis symptoms, but one new study could change that. This study sets out to prove that 3-day periodic cycles of fasting mimicking diets can reduce multiple sclerosis symptoms. Choi et al. used clinical trials on mice with similar symptoms to multiple sclerosis patients in order to show the effects fasting can have on multiple sclerosis symptoms.
Researchers specifically focused on low calorie, low protein, and even ketogenic diets when trying to produce fasting mimicking diets. After giving mice these types of diets over 3-day cycles, researchers began to see vast improvements in certain aspects of the mices' health. The first thing they noticed was that it reduced disease severity when using an experimental autoimmune encaphalomyelitis model. This could mean that fasting mimicking diets could reduce disease severity in neurodegenerative diseases like multiple sclerosis. The diets do this by reducing the reactivity and levels of autoimmune cells that cause multiple sclerosis symptoms to worsen.
Another beneficial aspect of fasting mimicking diets was that they reduced the number of immune cells infiltrating the spinal cord. These autoimmune cells are often the cause of many of these degenerative diseases as they end up attacking the body's healthy cells. Researchers believed that another related effect was an increase in regulatory T cells, which also prevented autoimmune cells from getting into the spinal cord.
Fasting mimicking diets were also shown to reduce TH1 and TH17 in the spinal cord, inflammatory cytokines that could lead to inflammation of the whole system. This effect may be regulated by temporary elevation of corticosterone, dampening of T cell activation, and reduced APCs in the spinal cord. Overall though, inflammation of the spinal cord should be reduced when using fasting mimicking diets.
Fasting mimicking diets also stimulate myelination by promoting oligodendrocyte regeneration. Myelination the process of propagating oligodendrocyte precursor cells to form oligodendrocytes to create new myelin sheaths on demyelinated axons in the central nervous system. Myelination is an important aspect of a healthy central nervous system as the sheaths prevent damage and inflammation in the central nervous system. Multiple sclerosis is known to cause demyelination at a rapid rate, so stimulating myelination could do wonders in reducing the damage MS can do to the central nervous system.
Lastly, researchers conducted a randomized trial to determine if fasting mimicking diets were safe and/or feasible for relapsing-remitting multiple sclerosis patients. The trials showed that there was a high compliance rate in patients who partook in the trials, and that disease severity was reduced for the most part. There were also very few adverse events reported when patient's undertook the diets. There still needs to be more testing done to ensure the diets' safety and efficacy, but based upon these trials the outlook is quite promising.
What Does It All Mean?
Researchers in the first study found that autophagy (the process of eliminating waste in the body's cells) is increased in patients with multiple sclerosis. A different research team found that diets that mimicked fasting (low calorie, low protein, ketogenic etc.) reduced some adverse effects of multiple sclerosis in mice.
Those who read through the information above may wonder how the two studies are at all possibly related. Basically, fasting mimicking diets tend to have the same effects as autophagy (reduction of waste and T cells) which means that autophagy may be beneficial after all. Since these diets tend to have benefits relating to multiple sclerosis, further studies may confirm that autophagy can have the same protective effect. If autophagy is actually protective, these diets could work alongside increased autophagy even more and reduce the symptoms of multiple sclerosis (all without the use of drugs). It also could lead to the introduction of better antibiotics and treatment plans for multiple sclerosis patients in the future. We do have to stress that these studies are all very recent and likely will need more trials before becoming standard treatments. Make sure to talk to your doctor about trying any specific diet or treatment for your own multiple sclerosis.