ALS Tied To Increased Fat Oxidation (FAO), Increasing Glucose May Treat It

haidut

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I made a few posts in the past about ALS characterized by adrenal hyperactivity and suppressed gonadal function, as well as mitochondrial dysfunction and copper deficiency. Also, non-familial ALS is known to occurs 4-5 times more often in active/retired elite athletes. All of these findings strongly suggest ALS is linked to stress and dysregulated metabolism. The study below explains that the metabolic dysregulation of ALS is tied to increased fatty acid oxidation (FAO) and increased glycolysis due to glucose wastage as a result. The increased requirements of glucose and its increased wastage due to upregulated glycolysis are apparently a major reason for the progressive character of this condition. As such, providing extra (5-10 higher than normal dietary levels) dietary glucose enabled the affected neurons to survive much longer and be much more resilient to degeneration. So, according to the studies below, the metabolic phenotype of ALS is not much different from cancer and diabetes (type I). As such, just like them, ALS is also a wasting disease. If providing extra dietary glucose and/or restoring glucose metabolism with chemicals like DCA is therapeutic to ALS, might the same approach work in cancer and diabetes I?? My guess is YES.

Now, the study only looked at supplying extra glucose to the malfunctioning neurons. It did not look at why patients with ALS waste away so rapidly. The culprit, hinted at by the increased FAO, is increased lipolysis. It is that same uncontrolled lipolysis that is responsible for the wasting seen in diabetes I and (partially) cancer as well. So, considering the benefits of niacinamide and aspirin in restraining excessive glycolysis, I'd venture a guess that adding either one of those nutrients to the extra dietary glucose regimen would be dramatically more effective.

Peat spoke in one interview about a friend of his who was diagnosed with ALS about 20 years ago and is not only still alive but highly active and gainfully employed. His secret? Apparently, 3-5 tablets of aspirin daily when the disease was first starting and then decreasing this to 1 tablet daily about 6 months later and continuing on 1 tablet daily to this day. The late Stephen Hawking was diagnosed with ALS in the 1960s and survived for decades, albeit with severe motor deficits. Later on in his life doctors started questioning if his condition was ALS because, you know, nobody can survive with ALS for so long. I wonder if Mr. Hawking's self-professed habit of taking an aspirin tablet twice a week had something to do with it...

Metabolic Dysregulation in Amyotrophic Lateral Sclerosis: Challenges and Opportunities. - PubMed - NCBI

"...These models provide the tools for genetic and dietary interventions that can distinguish between cause and consequence. For example, although the primary cause remains unknown, in ALS muscles, there seems to be a reduction in glycolysis that is compensated by utilization of alternate fuels such as fatty acids (Figure 1). In contrast, in motor neurons, the impairment in mitochondrial function may lead to compensatory mechanisms that counterbalance the defects in oxidative phosphorylation such as increased glycolysis as reported in cultured cells, or altered interactions with lactate producing glial cells.

Another study using asymptomatic SOD1G86R mice indicated decreased glucose handling in glycolytic muscles of the diseased animals [43]. This is due to concerted effects caused by downregulation of the key glycolytic enzyme phosphofructokinase 1 (PFK 1), and upregulation of pyruvate dehydrogenase kinase 4 (PDK4), an enzyme that inhibits pyruvate dehydrogenase complex through phosphorylation, thus blocking conversion of pyruvate into acetyl-coA. As a consequence, the lipid pathway was stimulated in these animals as early as during the pre-symptomatic stage, and remained active till end stage of the disease, thus switching the fuel preference towards fatty acids by suppressing glucose utilization. Consistent with this, treatment with DCA, a specific inhibitor of PDK, restored normal mRNA expression of Pdk and Pfk1 mRNAs, and resulted in decreased expression of denervation and atrophy markers. This was further translated at the functional level by restoration of muscle strength, larger muscle fibers and overall weight gain in DCA-treated animals compared to non-treated SOD1G86R mice. Thus altogether, this and previous reports show that as the glycolytic muscles progressively lose their ability to utilize glucose, they switch to lipids as an alternate energy source, and that, this metabolic switch happens largely in the early pre-symptomatic stage.

Glycolysis upregulation is neuroprotective as a compensatory mechanism in ALS | eLife

People with ALS May Benefit From More Glucose

"...Increased glucose, transformed into energy, could give people with amyotrophic lateral sclerosis, or ALS, improved mobility and a longer life, according to new findings by a University of Arizona-led research team."

People with ALS use more energy while resting than those without the disease, while simultaneously they often struggle to effectively make use of glucose, the precise ingredient a body needs to make more energy. Experts have not known exactly what happens in a patient’s cells to cause this dysfunction or how to alleviate it. “This project was a way to parse out those details,” said Manzo, who described the results, published online in eLife, as “truly shocking.”

"...The study revealed that when ALS-affected neurons are given more glucose, they turn that power source into energy. With that energy, they’re able to survive longer and function better. Increasing glucose delivery to the cells, then, may be one way to meet the abnormally high energy demands of ALS patients. “These neurons were finding some relief by breaking down glucose and getting more cellular energy,” Manzo said."

“The fact that we uncovered a compensatory mechanism surprised me,” Zarnescu said. “These desperate, degenerating neurons showed incredible resilience. It is an example of how amazing cells are at dealing with stress.” The novelty of the findings partially lies in the fact that metabolism in ALS patients has remained poorly understood, Zarnescu said."

"...Their findings were consistent with a pilot clinical trial, which found a high carbohydrate diet was one possible intervention for ALS patients with gross metabolic dysfunction. “Our data essentially provide an explanation for why that approach might work,” Zarnescu said. “My goal is to convince clinicians to perform a larger clinical trial to test this idea.”
 

haidut

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I wonder if a high carb low fat diet would help Parkinson’s people.

It should, but I think increasing salt intake may be even more helpful given the recent post about low SERT expression in PD. SERT functionality is sodium-dependent.
 

haidut

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@haidut this is fantastic. You are posting amazingly useful material here. Thank you!!!

Thanks :):
Check out the other post on MS. Basically, both MS and ALS may turn out to be the same "spectrum" of diseases, as doctors like to say.
 
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Thanks :):
Check out the other post on MS. Basically, both MS and ALS may turn out to be the same "spectrum" of diseases, as doctors like to say.

I have found that increasing CO2 (using Buteyko for instance) is incredibly helpful for MS. It may cure MS.
 

haidut

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I have found that increasing CO2 (using Buteyko for instance) is incredibly helpful for MS. It may cure MS.

We are not allowed to say cure when it comes to officially named conditions. So, I would restate that increasing CO2 may cause "permanent remission" of MS :):
 

Inaut

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@ecstatichamster did you do a Buteyko course or read a book? I'm pretty consistent with breathing through my nose but I'd like to learn a proper/effective techique. Right now its 4 second inhale, 7 sec exhale, 20 second breath hold.
 

Regina

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Thanks :):
Check out the other post on MS. Basically, both MS and ALS may turn out to be the same "spectrum" of diseases, as doctors like to say.
Both fantastic. Thanks so much for these finds. The ALS one is simple enough to send around to friends and family.
 

Kelj

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People with ALS use more energy while resting than those without the disease,

Isn't this the much touted effect of exercise? Could this explain the high incidence of ALS among athletes? I would describe it as a persistent under supply of energy relative to expenditure.

It is interesting to me that Stephen Hawking said,

"According to The Telegraph, Professor Hawking released a public advisory on why people need to stop eating too much. He emphasized that this gluttony leads to serious health problems and causes even death due to complications from obesity. "We eat too much and move too little," the famous physicist and cosmologist added."

He was brilliant, but I think this was very bad advice....the advice that has caused so much trouble. We often say,
"(whatever) isn't rocket science". Ray Peat has this to say:

"Nutrition is one of the most important sciences, and should certainly be as prestigious and well financed as astrophysics and nuclear physics, but while people say “it doesn’t take a brain surgeon to figure that out,” no one says “it doesn’t take a nutritionist to understand that.”

The science of what is happening when food interacts with our bodies is complicated. Some, like Haidut, have truly accumulated a lot of knowledge which can help us tremendously, and more importantly, keep seeking knowledge. I am always stunned, however, by how many times the simple advice of just eat, and eat a wide variety of foods and enough to support your activity is at the bottom of the research.
 

haidut

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Isn't this the much touted effect of exercise? Could this explain the high incidence of ALS among athletes? I would describe it as a persistent under supply of energy relative to expenditure.

Yes, and is also seen in cancer and diabetes and the whole process is driven by excessive/uncontrolled lipolysis. There is a study I posted on the forum years ago showing that if lipolysis reaches a certain critical level the organism goes into hypercatabolic mode because that excessive lipolysis almost fully blocks glucose oxidation and the body interprets the blockage of glucose as an energy deficiency so it keeps increasin adrenaline and cortisol to provide even more fat and glucose from tissues. If this is not stopped by something like insulin in case of diabetics then the person dies from wasting away within weeks. I do not see any reason why the same lipolysis-blocking methods should not work in something like cancer or ALS. Giving extra glucose is one way to block excessive lipolysis and apparently it worked. So should niacinamide, aspirin, etc.
 

Kelj

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There has been a mini experiment going on in my family which illustrates this perfectly. We felt that our family's health was going south following a low carb diet. We decided to institute a recovery by eating ad libitum and emphasizing sugars and other carbs. One of us had been an almost professional level exerciser. The recovery of health has definitely been a longer and harder process for this person. Although we all started out overweight by the bmi charts, the recovery was characterized by weight gain then weight loss until normal weight was achieved, except where the heavy exerciser was concerned. This person ate more than before, but lost weight rapidly until a typical anorexic physique (the stereotype physique, I should say) was obtained. This was turned around by first, the realization that for these habitual over exercisers, the metabolism has been seriously altered. We realized that the calorie amount that the impaired digestive tract felt like eating was not enough. This person had to persist in eating well above the minimum calorie requirement for age, height and gender. Counting calories to achieve this high level of intake was absolutely crucial. Ensuring plenty of sugar was equally crucial. Heavy exercise requires some seriously high energy intake to support it. This has been a dangerous lesson to learn first hand.
 

haidut

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Heavy exercise requires some seriously high energy intake to support it. This has been a dangerous lesson to learn first hand.

Thanks for sharing. Glad everybody got better.
Btw, Michael Phelps would fully agree with your assessment. He was starting to become anorexic about a year ago but in his case it was alcohol abuse that was interfering with ability to absorb, digest and utilize food.
 
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