I am inviting you to think seriously about this idea : What if MS is nothing else but Diabetes ?. I know it may sound crazy, but just keep an open mind. Let’s look at the evidence.
Sugar metabolism and brain health
Sugar metabolism is abnormal in MS (and other related conditions)
Anti-diabetes drugs Metformin and Pioglitazone help treat MS
Altered metabolism of sugar in MS- more details and why is not detected by blood tests
MS: Striking similarities with diabetes type 1, 2 and 3
Solutions to altered metabolism of sugar
My opinion
1.Sugar metabolism and brain health
Your brain needs glucose for energy, to keep the the brain cells healthy and generate neurotransmitters our body needs sugar(glucose) to generate energy (in the form of ATP). Although the human brain is very little, only 2% of the body weight, it uses 25% of the total glucose, and the energy requirement is highest in the cells of the adult brain [1]. In the brain, this energy from glucose will be used for brain cells survival and generate neurotransmitters [2].
2.Sugar metabolism is abnormal in MS
The brain does not get enough glucose, causing mitochondrial dysfunction and neurodegeneration. One molecule breaks down into 2 molecules of pyruvate during a process called glycolysis. Since 1950 (that’s almost 7 decades ago !) scientists discovered that MS is associated with a defect in pyruvate metabolism, as the levels of blood pyruvate (both fasting and after eating) were higher in people with MS during relapse.
Normal cell metabolism (aka cell respiration)
Glucose——->Pyruvate——–> CO2+ 32 ATP molecules
There is some evidence that the metabolism of sugar starts to malfunction before neurodegeneration in MS , and the following mechanism has been proposed :
The absorption and use of glucose of the brain decreases, leading to mitochondrial dysfunction (meaning less ATP molecules) and then followed by the signs of brain degeneration (i.e. brain cells will start to degenerate (axonal atrophy) and/ or die (neuronal loss ) [3], [4]. As the disease progresses, there will be more degeneration and the sugar metabolism is further reduced . A vicious cycle which makes things worse over time.
One study found that people with MS had decreased sugar metabolism in specific brain areas (in case you want to know..prefrontal, premotor, supplementary motor areas, putamen areas of the brain ) compared with those without MS , and that the poor sugar metabolism in the brain correlates with fatigue [5].
Although a small study by design, this study gives us a big warning sign ……40 percent of the brain can’t work at best because has limited glucose available (remember, the glucose is needed for cell survival and neurotransmitter production ? ) This study shows that individuals with MS have a lower glucose uptake in 40% of the brain when compared with healthy people [6].
The impairment in sugar metabolism of the brain can also explain the reduced brain volume and enlarged ventricle (both findings associated with MS) [7]. Defective sugar metabolism is linked with abnormal fat metabolism and protein metabolism as they are all connected (the metabolism of fats and proteins will be covered in details in other posts) .
I will just give an example here : insulin resistance causes changes in certain fats ( lipoproteins) in MS [8]. The lipoprotein ApoA-I is particularly important for brain health as it prevents neurodegeneration and inflammation, and promotes the repair of the nerve cells [9], [10].
Optimizing the metabolism of fat is very important, considering that the brain is the most fat- rich organ, and the myelin sheath destroyed by MS is 70% fat. Insulin resistance in people with MS also correlates with more disability [11].
3. Anti-diabetes drugs Metformin and Pioglitazone can help reverse MS
Anti-diabetes drugs found to significantly improve symptoms and reduce number of lesions on MRI
Back to my ideea… what IF MS is nothing else than diabetes ? That means that anti-diabetes drugs could help ? Well, they do help. Pioglitazone, an FDA-approved drug used to treat type 2 diabetes had been found to help reverse MS. Initially, this drug was found in animal models of MS to delay the onset of the diseases and decrease the severity of symptoms . In humans, pioglitazone was studies for both safety and efficiency in secondary MS . This case study reveals dramatic improvement with pioglitazone ( 15 mg daily increased by 15 mg biweekly to 45 mg ): this drug helped improved the weight, cognition, attention span , strength, coordination and overall neurological function. Depression also improved,as noted by increased stamina and well being [12].
Do you want to know the result of a 2016 study published in the JAMA ?
“Of 50 patients with MS, after 6 months of treatment, 20 patients with MS who were treated with metformin and 10 who received pioglitazone showed a significant decrease in the number of new or enlarging T2 lesions as well as of gadolinium-enhancing lesions”…
(more technical findings: Compared with controls, both treatments led to a decrease in mean (SD) leptin levels and increase in mean (SD) adiponectin serum levels. Mean (SD) number of myelin basic protein peptide-specific cells secreting interferon γ and interleukin (IL)-17 were significantly reduced in patients receiving metformin compared with controls.. Patients treated with pioglitazone showed significant decreases in the mean (SD) number of myelin basic protein peptide-specific cells secreting IL-6 and tumor necrosis factor compared with controls; tumor necrosis factor. Both metformin and pioglitazone resulted in a significant increase in the number and regulatory functions of CD4+CD25+FoxP3+ regulatory T cells compared with controls. [13].
Note : this study was conducted in obese individuals with MS who also had metabolic syndrome (Metabolic syndrome is a cluster of conditions — increased blood pressure and blood sugar levels, excess body fat around the waist, and abnormal cholesterol or triglyceride levels) while the other study (case study) mentioned above was in a person with MS who was underweight (30 Kgs)
Liraglutide, another drug with anti-diabetes, weight reducing drugs showed positive effects in the animal model of MS- significantly reduced the disease severity and neurodegeneration while raising the antioxidant levels. Would be interesting to see studies in humans [14].
Technical : Mechanism of action metformin : metformin decreases Th17 and raises Treg cell percentages along with the levels of associated cytokines. Suppressed activation of mTOR and its downstream target, HIF-1α, likely mediated the protective effects of metformin [15].
Metformin is considered a future therapy for neurodegenerative diseases, according to some scientists [16].
Mechanism of action pioglitazone : pioglitazone is a PPARγ agonist. PPARγ plays a key role in regulation of glucose and lipid metabolism is markedly increased in CSF of MS patients [17]. PPAR-γ has anti-inflammatory and neuroprotective effects and PPAR-γ agonists protect OL progenitors against the maturational arrest induced by the inflammatory cytokine TNF-α by affecting mitochondrial functions [18].
Altered metabolism of carbs in MS- more details and why is not detected by blood tests
Blood glucose levels can be normal, even if there is an impaired metabolism of sugar Disturbances in the metabolism of sugar contributes to neurodegeneration, this is not a new idea. People with MS have decreased insulin sensitivity compared with healthy individuals [19] , and increased insulin resistance (reduced ability of insulin to stimulate glucose utilization) [20] and abnormally low concentration of insulin in the blood in the brain area (a condition called brain or central hypoinsulinemia) .
If we look at the hormone insulin, it is an anabolic hormone that plays a key role in energy and metabolism. Abnormal insulin levels lead to increased oxidative stress, mitochondrial dysfunction and destruction (which are found in MS, Parkinson’s and Alzheimer’s disease) [21].
Technical : Hyperinsulinemia appears to develop as a compensatory mechanism in the context of insulin resistance to overcome receptor insensitivity and maintain glucose homeostasis. Insulin receptors are widely expressed in brain regions that are prone to neurodegeneration (for example medial temporal lobe and prefrontal cortex, which are involved in long-term memory and working memory) . However, insulin must be transported from the periphery because there is very little insulin synthesized in the brain) . Paradoxically, this peripheral hyperinsulinemia resulting from insulin resistance is correlated with brain (aka central) hypoinsulinemia because of saturation of the blood-brain barrier transport mechanism [22], [23], [24] .
There is an increased levels of activity of extra mitochondrial pathways of glucose metabolism (as shown by increased levels of lactate, sorbitol, and fructose in the CSF of SPMS patients and to a lesser extent to RRMS patients). These changes may contribute to mitochondrial dysfunction and neuroaxonal degeneration (typically found in MS progression) [25].
Why your blood sugar levels may be normal, and yet the metabolism of glucose is impaired ?
Generally speaking, most people with insulin resistance will not notice symptoms, thus not get medical attention. The body will try to compensate and produce extra insulin for many years (yet, we’ve seen that in MS the brain does not get enough glucose and even that amount is not used efficiently ) . When the body’s insulin production fail to keep with the demand, then hyperglycemia will develop (this is detected by blood tests-that check the glucose levels). Once the glucose reaches a high enough level, then diabetes type 2 occur. Both hyperinsulinemia and insulin resistance are linked with altered levels of lipids/cholesterol.
Symptoms of insulin resistance include : feeling hungry constantly, sleepy after eating, craving sweets (especially after meals), problems loosing excess weight. Typical symptoms of diabetes like increased appetite, thirst and urination can also occur. All these symptoms may aggravate from eating too much, too little exercise or stress.
MS -Striking similarities with diabetes type 1, 2, and 3
All three forms of diabetes (and MS) have one thing in common : altered metabolism of sugar
Everyone knows the most common form of diabetes found mostly in adults, which is type 2 diabetes. Insulin resistance is a key trigger for this condition, it is earliest detectable defect in pre-diabetic individuals)[26].
Type 1 diabetes affects younger people, and just like MS- it has an autoimmune component. Interestingly. A team of researchers from the Hospital of Sick Children, Toronto, Canada found that MS and type 1 diabetes are closely linked conditions. “Much to our surprise, we found that immunologically, type I diabetes and multiple sclerosis are almost the same – in a test tube you can barely tell the two diseases apart,” said Dr. Dosch, the study’s principal investigator. He also found that the autoimmunity targets both the central nervous system and the pancreas in both type 1 diabetes and MS . The researchers also point that a major environmental factor for diabetes is exposure to cow’s milk ( read my posts about the harms of cow s milk for those with MS and its role in autoimmunity ) [27]. Type 1 diabetes also increases significantly the risk for MS [28].
Finally type 3 diabetes was more recently discovered, while researching Alzheimer’s disease (note: Alzheimer s disease shares many similarities with MS). Basically type 3 diabetes found in AD is indeed a form of diabetes which (unlike diabetes type 2) selectively involved the brain but otherwise has molecular and biochemical features that overlap with type 1 and type 2 diabetes [29].
Solutions to altered metabolism of sugar
By improving insulin resistance, you will help your brain cells use glucose more efficiently. Your brain can use not only glucose as a fuel, but also ketone bodies . How lucky we are to have alternate source of energy available ! (by the way, lactate is another source of energy for brain, however- glucose and alanine are the predominant sources of lactate, and the metabolism of lactate is also impaired in MS [38], [39] ).
Besides treating the insulin resistance, another viable solution to impaired sugar metabolism is to let the brain use ketone bodies as a source of energy . Unlike sugar metabolism which is reduced , the ketone bodies metabolism is not affected. For this purpose, the body has to be in a state of ketosis which can be achieved with ketogenic diet, fasting, supplements that promote ketosis and fasting mimicking diet.
In addition, insulin resistance can be improved in other ways like : supplements (for example probiotics [30] , exercise like HIIT [31] or special procedures like fecal microbiota transplantation [33], [34].
7. Impaired sugar metabolism plays a key role in MS, totally worth looking into it. MS closely resembles type 3 diabetes, with overlapping features of diabetes type 1 and 2. Using therapies and research for diabetes could be extremely useful for MS – we have already seen the benefits of the anti-diabetes drugs,and would be great to see more studies. Pioglitazone is a PPAR-γ agonist, it looks more effective (but not as safe as metformin) [35] , [36], [37]. Would be interesting to see how insulin therapy would work for MS.
Considering CAM therapies, I have some really good news : certain diets/foods , supplements and alternative therapies can effectively manage diabetes. Plus they have an excellent safety profile, too.
The defective metabolism of sugar plays a key role not only in the progression, but also in the development of MS, I think. It makes a lot of sense to look at hormonal, and metabolic aspects of MS- because right now MS is considered just a simple autoimmune, degenerative condition affecting the central nervous system .
