This Is MS Multiple Sclerosis Knowledge & Support Community

The following article appeared in the September 2010 issue of the AARP Bulletin, although online it is attributed to the May issue.

http://www.aarp.org/health/conditions-t ... sease.html

This article does not mention Dennis J Selkoe (whose ideas were discussed on page 5 of this thread), but I think his ideas are fundamental to this new hypothesis that Alzheimer's disease is the result of clumps of amyloid beta protein called oligomers.

I continue to believe that excess insulin plays a key role in both MS and Alzheimer's. In Alzheimer's Disease, the Insulin Degrading Enzyme (IDE) is drawn first to the insulin (and used up in breaking down that hormone) and then is not available to break down the amyloid beta, allowing it to accumulate in the brain.

In MS, excess insulin is circulating in the bloodstream, causing damage to the blood vessels, even permeating the blood brain barrier, and triggering the immune system (including cholesterol deposits intended to repair the damage, but which may account for narrowing, i.e., stenosis).

I agree. I have hypoglycemia. I believe that cortisol drives down insulin and so in its exhaustion insulin might have its way. I hate insulin cuz it makes me so nervous and angry. insulin is a key that unlocks the cells so energy can enter. look up cortisol on wikipedia and then see all the things that that hormone is responsible for and in its absence would be disasterous. one thing is the prevention of the proliferation of T cells. another is that it moves sodium into the cells and potassium out. another is moving gastric acid into the stomach. what happens without the acid is too much bacteria and in my opinion too much vitamin K =highplatelets and too much folate also would disrupt B-12 there in the gut. it goes on and on but these hormones are the key YES!!

Although I posted the following information a few months ago to Leonard's thread, "I think I found it…," I feel that the information is also relevant to ideas in this thread:

I now think that "insulin resistance hypothesis" is more appropriate than "excess insulin hypothesis" as the starting point for MS.

The following article describes insulin resistance, and the list of symptoms even includes hemochromatosis, which others on this website have long suspected of being involved in their MS diagnosis:

http://www.news-medical.net/health/What ... tance.aspx

In the following article, the Yale researcher describes his hypothesis for insulin resistance:

"Our hypothesis was that the metabolic syndrome is really a problem with how we store energy from food," Shulman explained. "The idea is that insulin resistance in muscle changes the pattern of energy storage."

After providing the study's subjects with two meals high in carbohydrates, Shulman and his colleagues turned to magnetic resonance spectroscopy to measure the production of liver and muscle triglyceride, the storage form of fat, and of glycogen, the storage form of carbohydrates. "What we found is that (insulin) sensitive individuals took the energy from carbohydrate in the meals and stored it away as glycogen in both liver and muscle," said Shulman.

In the insulin resistant subjects, the energy obtained from their carbohydrates rich meals was rerouted to liver triglyceride production, elevating triglycerides in the blood by as much as 60 percent and lowering HDL cholesterol (the good cholesterol) by 20 percent. "In contrast to the young, lean, insulin-sensitive subjects, who stored most of their ingested energy as liver and muscle glycogen, the young, lean, insulin-resistant subjects had a marked defect in muscle glycogen synthesis and diverted much more of their ingested carbohydrate into liver fat production," Shulman and his colleagues reported.

"What we see," he noted, "is alterations in patterns of energy storage. An additional key point is that the insulin resistance, in these young, lean, insulin resistant individuals, was if MS independent of abdominal obesity and circulating plasma adipocytokines, suggesting that these abnormalities develop later in the development of the metabolic syndrome."

The new findings promise to help untangle the early molecular events of a syndrome at the root of one of the world's most significant health issues. "Knowing how insulin resistance alters energy storage before it leads to more serious problems can help those susceptible prevent the onset of the metabolic syndrome," Shulman said.

Another key observation was that skeletal muscle insulin resistance precedes the development of insulin resistance in liver cells, and that fat production in the liver is increased. "These findings also have important implications for understanding the pathogenesis of nonalcoholic fatty liver disease, one of the most prevalent liver diseases in both adults and children Shulman said.

http://www.news-medical.net/news/2007/07/17/27656.aspx

This focus on energy storage is reminiscent of Dr. Terry Wahls' ideas on mitochondria. Dr. Shulman's comment that insulin resistance alters energy storage before leading to more serious problems suggests to me that insulin resistance may be the culprit leading to MS. Apparently, skeletal muscle insulin resistance is the first step toward general insulin resistance (and then MS? Nonalcoholic fatty liver disease? Other "autoimmune diseases?").

I find hope in the article's conclusion that exercise can counter skeletal muscle insulin resistance, I need to find time for more exercise!

If insulin resistance is implicated in MS, then the causes of insulin resistance will be important to us too:

Since I have suspected that glucosamine, a sugar-based supplement, and all artificial sweeteners stimulated the pancreas to produce insulin, I found the article's sentence especially interesting:

http://www.news-medical.net/health/Caus ... tance.aspx

An American study has shown that glucosamine (often prescribed for joint problems) may cause insulin resistance.

Has anyone seen this "American study?"

lyndacarol wrote:Since I have suspected that glucosamine, a sugar-based supplement, and all artificial sweeteners stimulated the pancreas to produce insulin, I found the article's sentence especially interesting:

http://www.news-medical.net/health/Caus ... tance.aspx

An American study has shown that glucosamine (often prescribed for joint problems) may cause insulin resistance.

Has anyone seen this "American study?"

I have not seen the study they refer to. Interestingly, the Mayo Clinic recently noted on their site that glucosamine does not affect insulin resistance. The references are near the bottom of the page linked below.

[color=blue]Mayo Clinic[/color] wrote:Question
Glucosamine: Does it affect blood sugar?
Is it safe to take glucosamine supplements if I have diabetes?
Answer
from Maria Collazo-Clavell, M.D.

Even though glucosamine is technically a type of sugar, it doesn't appear to affect blood glucose levels or insulin sensitivity. Some preliminary research had suggested that glucosamine might worsen insulin resistance, which can contribute to increases in blood sugar in people with type 2 diabetes. But subsequent studies refuted these findings.

Glucosamine is one of the most popular dietary supplements sold in the United States, although study results have been mixed regarding its ability to reduce osteoarthritis pain. While glucosamine doesn't appear to affect glucose levels or insulin sensitivity, the supplement can interact with other medications you might be taking — such as warfarin (Coumadin), a blood thinner.

NHE

NHE – a few more thoughts:

It is my understanding that "hyperinsulinemia (excess insulin)" is synonymous with "insulin resistance." The news-medical article stated "An American study has shown that glucosamine (often prescribed for joint problems) may cause insulin resistance."

Perhaps glucosamine does not raise blood glucose, just as the Mayo Clinic article does state (thank you so much, NHE, for that information), but affects only the pancreas and its insulin secretion.

Several years ago I read a Discover magazine article on artificial sweeteners; it was mentioned that artificial sweeteners increased insulin production in a mouse study. I suspect the same happens with humans. (Elsewhere, I have read that even a sweet sensation in the mouth causes the pancreas to secrete insulin.)

Although blood glucose is most commonly the trigger for insulin secretion, there may be MANY other reasons for the pancreas to pump out the hormone – the "sweetness" of artificial sweeteners, even infection of the pancreas by a virus or bacteria (even the inflammation of pancreatitis). I think the damaging culprit is insulin, not necessarily glucose.

Just sharing a few of my thoughts.

Hi Lynda,

.. and the insulin resistance is caused by the ligands that block the Vitamine D nuclear receptor.
The glucose transport will be inhibited.
And the poor cells will die (long term); or as a minimum the ion pump will not be charged (fast) enough (short term) giving typical symptoms..
The whole pallet of inflammatory diseases will need to be "re-engineered".
http://www.discoverymedicine.com/Shaopi ... infection/

The VDR dysfunction is the culprit of MS; of course the vascular narrowings in the neck cause the BBB to break creating the right conditions for MS to develop..
see this page (18) at
http://www.thisisms.com/forum/general-d ... 8-255.html

Leo

lyndacarol wrote:NHE – a few more thoughts:

It is my understanding that "hyperinsulinemia (excess insulin)" is synonymous with "insulin resistance." The news-medical article stated "An American study has shown that glucosamine (often prescribed for joint problems) may cause insulin resistance."

Perhaps glucosamine does not raise blood glucose, just as the Mayo Clinic article does state (thank you so much, NHE, for that information), but affects only the pancreas and its insulin secretion.

Several years ago I read a Discover magazine article on artificial sweeteners; it was mentioned that artificial sweeteners increased insulin production in a mouse study. I suspect the same happens with humans. (Elsewhere, I have read that even a sweet sensation in the mouth causes the pancreas to secrete insulin.)

Although blood glucose is most commonly the trigger for insulin secretion, there may be MANY other reasons for the pancreas to pump out the hormone – the "sweetness" of artificial sweeteners, even infection of the pancreas by a virus or bacteria (even the inflammation of pancreatitis). I think the damaging culprit is insulin, not necessarily glucose.

Just sharing a few of my thoughts.

"Mike" might disagree that glucosamine does any harm to MSers.(SEE BELOW)

jackD

Glucosamine-like supplement suppresses multiple sclerosis attacks

UCI study shows promise of metabolic therapy for autoimmune diseases
— Irvine, Calif., September 30, 2011 —

A glucosamine-like dietary supplement suppresses the damaging autoimmune response seen in multiple sclerosis, according to a UC Irvine study.

UCI’s Dr. Michael Demetriou, Ani Grigorian and others found that oral N-acetylglucosamine (GlcNAc), which is similar to but more effective than the widely available glucosamine, inhibited the growth and function of abnormal T-cells that in MS incorrectly direct the immune system to attack and break down central nervous system tissue that insulates nerves.

Study results appear online in The Journal of Biological Chemistry.

Earlier this year, Demetriou and colleagues discovered that environmental and inherited risk factors associated with MS — previously poorly understood and not known to be connected — converge to affect how specific sugars are added to proteins regulating the disease.

“This sugar-based supplement corrects a genetic defect that induces cells to attack the body in MS,” said Demetriou, associate professor of neurology and microbiology & molecular genetics, “making metabolic therapy a rational approach that differs significantly from currently available treatments.”

Virtually all proteins on the surface of cells, including immune cells such as T-cells, are modified by complex sugar molecules of variable sizes and composition. Recent studies have linked changes in these sugars to T-cell hyperactivity and autoimmune disease.

In mouse models of MS-like autoimmune disease, Demetriou and his team found that GlcNAc given orally to those with leg weakness suppressed T-cell hyperactivity and autoimmune response by increasing sugar modifications to the T-cell proteins, thereby reversing the progression to paralysis.

The study comes on the heels of others showing the potential of GlcNAc in humans. One reported that eight of 12 children with treatment-resistant autoimmune inflammatory bowel disease improved significantly after two years of GlcNAc therapy. No serious adverse side effects were noted.

“Together, these findings identify metabolic therapy using dietary supplements such as GlcNAc as a possible treatment for autoimmune diseases,” said Demetriou, associate director of UCI’s Multiple Sclerosis Research Center. “Excitement about this strategy stems from the novel mechanism for affecting T-cell function and autoimmunity — the targeting of a molecular defect promoting disease — and its availability and simplicity.”

He cautioned that more human studies are required to assess the full potential of the approach. GlcNAc supplements are available over the counter and differ from commercially popular glucosamine. People who purchase GlcNAc should consult with their doctors before use.

Lynda, could you please have a look at this: http://intelegen.com/nutrients/insulin_ ... weight.htm

and in particular at its recommendations:

A total approach to insulin resistance requires an understanding of its multifaceted aspects and the increased necessity for nutritional and lifestyle interventions. The use of diet, exercise, nutritional supplements and medications such as metformin are central not only to restoring metabolic balance, but for biological age reversal and life extension as well. The following program is recommended for optimal results.

1. Follow a low glycemic or BDK diet

2. Exercise regularly

3. Take 200-800 mcg of chromium and 50-150 mcg of vanadium daily

4. Take 500 mg of metformin two or three times per day or five to six capsules of VRP's GluControl.

What is your appreciation? does it resonate with things in your thread?

Leo

http://www.hardickchiropractic.com/inde ... order.html
Dr. Hans Michael Dosch, the study’s principal investigator and senior scientist at SickKids in Toronto, had previously concluded in a 1999 paper that there were surprising similarities between diabetes and multiple sclerosis, a central nervous system disease.

well, that's what the establishment might have liked... whow what prospect for study..

but the reality of course is that it is just the other way around: that multiple sclerosis is, just like diabetes, not a neurological disorder but a metabolic disease with some neurological "side" effects
(see for instance http://www.thisisms.com/forum/general-d ... 15188.html ).

http://www.thisisms.com/forum/general-d ... 18911.html
A related post regarding MS like disease induced in mice with diabetes

CureOrBust wrote:http://www.thisisms.com/forum/general-d ... 18911.html
A related post regarding MS like disease induced in mice with diabetes

Thank you.
I quote from the link: They found that the influx of certain immune cells, called macrophages, from the young mouse helped resident stem cells restore effective remyelination in the old mouse’s spinal cord.
This is possibly one path one could go and explore further ...

But I think there is a more direct route to tackle the disease, rather than to restore after things went wrong. I believe that the Vitamin D and in particular a dysfunctioning of the Vitamin D Receptor (VDR) due to commensal intestinal bacteria is the culprit of demyelination, slowing down both oligodendrocytes and Schwann cells to function properly and demyelination as a result.

This article makes the point: Autophagy [that is macro- micro- and chaperon mediated phagy] contributes to anti-aging, antimicrobial defense, and tumor suppression. The functions of autophagy overlap remarkably with those of the Vitamin D/VDR signaling.
http://www.discoverymedicine.com/Shaopi ... infection/

This is also the point where a low glucose diet and things like metformin come into the picture, see for example
http://intelegen.com/nutrients/insulin_ ... weight.htm
The Swank (low fat) diet may have precisely this effect and that is why it is working for MS.
I believe this was also Lynda's point.

Although gwa posted this Medical News Today article more than three years ago in the General Discussion forum, I think the second paragraph with its mention of adiponectin and insulin sensitivity requires that it be added to this "Insulin – Could This Be the Key?" thread as well: http://www.medicalnewstoday.com/releases/120456.php

Medical News Today
Link Found Between Bisphenol A And Metabolic Syndrome In Human Tissue
07 Sep 2008

New research from the University of Cincinnati (UC) implicates the primary chemical used to produce hard plastics - bisphenol A (BPA) - as a risk factor for metabolic syndrome and its consequences.

In a laboratory study, using fresh human fat tissues, the UC team found that BPA suppresses a key hormone, adiponectin, which is responsible for regulating insulin sensitivity in the body and puts people at a substantially higher risk for metabolic syndrome.

Metabolic syndrome is a combination of risk factors that include lower responsiveness to insulin and higher blood levels of sugar and lipids. According to the American Heart Association, about 25 percent of Americans have metabolic syndrome. Left untreated, the disorder can lead to life-threatening health problems such as coronary artery disease, stroke and type 2 diabetes.

Nira Ben-Jonathan, PhD, and her team are the first to report scientific evidence on the health effects of BPA at environmentally relevant doses equal to "average" human exposure. Previous studies have primarily focused on animal studies and high doses of BPA.

They report their findings in the Aug. 14, 2008, online edition of the journal Environmental Health Perspectives. This scientific data comes just before a key Federal Drug Administration meeting about the safety of the chemical in consumer products scheduled for Sept. 16, 2008.

"People have serious concerns about the potential health effects of BPA. As the scientific evidence continues to mount against the chemical, it should be given serious attention to minimize future harm," says Ben-Jonathan, a professor of cancer and cell biology at UC who has studied BPA for more than 10 years.

"Experimenting with human tissue is the closest we can come to testing the effects of BPA in humans. It's a very exciting breakthrough because epidemiological studies looking at BPA effects on humans are difficult since most people have already been exposed to it," she adds.

Scientists estimate that over 80 percent of people tested have measurable BPA in their bloodstream. The UC study was designed to mimic a realistic human exposure (between 0.1 and 10 nanomolar) so that a more direct correlation between human exposure and health effects could be drawn.

To conduct this study, the UC team collected fresh fat tissue from Cincinnati patients undergoing several types of breast or abdominal surgery. These samples included three types of fat tissue: breast, subcutaneous and visceral (around the organs).

Tissue was immediately taken to the laboratory and incubated with different concentrations of BPA or estrogen for six hours to observe how the varied amounts of BPA affected adiponectin levels. The effects of BPA were then compared to those of estradiol, a natural form of human estrogen.

They found that exposing human tissues to BPA levels within the range of common human exposure resulted in suppression of a hormone that protects people from metabolic syndrome.

"These results are especially powerful because we didn't use a single patient, a single tissue source or a single occurrence," she adds. "We used different fat tissues from multiple patients and got the same negative response to BPA."

----------------------------
Article adapted by Medical News Today from original press release.
----------------------------

UC's Eric Hugo, PhD, Terry Brandebourg, PhD, Jessica Woo, PhD, J. Wesley Alexander, MD, and Christ Hospital surgeon Jean Loftus, MD, participated in this study. The study was funded by grants from the National Institute of Environmental Health Sciences.

Source: Amanda Harper
University of Cincinnati

Article URL: http://www.medicalnewstoday.com/articles/120456.php



I am now intrigued with adiponectin. Could I be deficient in this hormone?

And thanks to NHE's General Discussion posting some time ago:

http://www.medterms.com/script/main/art ... ekey=17982

Source: http://www.medterms.com
MedTerms is the Medical Dictionary of MedicineNet.com

Definition of Adiponectin
Adiponectin: A protein hormone produced and secreted exclusively by adipocytes (fat cells) that regulates the metabolism of lipids and glucose. Adiponectin influences the body's response to insulin. Adiponectin also has antiinflammatory effects on the cells lining the walls of blood vessels.

High blood levels of adiponectin are associated with a reduced risk of heart attack. Low levels of adiponectin are found in people who are obese (and who are at increased risk of a heart attack).

Adipocytes produce and secrete a number of proteins, including leptin, adipsin, properdin, and tumor necrosis factor (TNF). An adipose tissue-specific factor was isolated and termed APM1 (AdiPose Most abundant gene transcript 1). The protein product of APM1 is adiponectin. The APM1 gene maps to chromosome 3q27.

I am consolidating this mention of AICAR with this thread on insulin – they seem to be related and it makes it easier for me to find the information:

http://www.thisisms.com/forum/post18262 ... se#p182623

The following information about the hormone irisin fits here in the same way:

http://www.medicalnewstoday.com/articles/240325.php

in the CCSVI forum, pairOdime posted very good information on the newly discovered hormone irisin:

http://www.thisisms.com/forum/post185031.html#p185031

Here is some very interesting information on a newly discovered hormone named Irisin. Some are suggesting possible implications for neurodegenerative conditions as well....very interesting.

http://www.ncbi.nlm.nih.gov/pubmed?term=irisin

http://www.nature.com/nature/journal/va ... 10777.html

http://scienceblog.com/51556/scientists ... rn-energy/


Quote:
The scientists said their findings merely scratch the surface of irisin’s multiple effects. They are continuing to explore the hormone’s possible benefits in metabolic diseases like diabetes, insulin resistance, and obesity, which constitute a growing epidemic around the world, as well as neurodegenerative illnesses like Parkinson’s disease.
Spiegelman added that as growing evidence implicates obesity and physical inactivity in cancer development, it’s conceivable irisin-based drugs may have value in prevention and treatment of the disease.

Nature. 2012 Jan 11. doi: 10.1038/nature10777. [Epub ahead of print]

A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis.

Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Boström EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Højlund K, Gygi SP, Spiegelman BM.

Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, Floor 11, Boston, Massachusetts 02115, USA.

Abstract
Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-γ co-activator-1 α (PGC1-α). Here we show in mouse that PGC1-α expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.

PMID:
22237023
[PubMed - as supplied by publisher]

Of course, there is no substitute for a proper diet and exercise when possible.

A video with information on functional medicine practitioners:
First up is Dr. Mark Hyman on diabesity; his opinion is that food is the best medicine; he urges 2 tests (Insulin Response Test & NMR Cholesterol Test); he states that insulin, the fat-storage hormone, causes belly fat and inflammation. He also discusses sensitivity to foods (dairy, gluten, corn, eggs, soy, etc.) which may also cause inflammation.

http://www.doctoroz.com/videos/dr-oz-s- ... tives-pt-2

Thanks to want2bike we have this presentation from Dr. Mark Hyman on Functional Medicine:



Although Dr. Wendy Warner, the fourth and last of these Functional Medicine doctors, is discussing weight gain/menopause, I think Dr. Oz's animation of the weight gain flowchart (about .30 in the video) has value to those of us with MS:

http://www.doctoroz.com/videos/dr-oz-s- ... tives-pt-6

We know that inflammation is involved in MS; I'm sure that excess insulin is also involved; visceral fat (internal fat around the organs) secretes cytokines (a.k.a. adipokines) as well as the estrogen Dr. Warner focuses on. Perhaps we have to interrupt the flow at several points: foods to reduce inflammation, diet to reduce insulin secretion, diet and exercise to reduce fat and the resulting cytokines. This may be the mechanism of Dr. Wahls' program.

I think we all need a Functional Medicine (disease detective) doctor – how do we find one?