Insulin--Could This Be the Key?

If it's on your mind and it has to do with multiple sclerosis in any way, post it here.
User avatar
CureOrBust
Family Elder
Posts: 3374
Joined: Wed Jul 27, 2005 2:00 pm
Location: Sydney, Australia

Re: Insulin--Could This Be the Key?

Post by CureOrBust »

a little (ok a lot) off topic, but I think this paper supplies a lot of good science in what happens to the body (and brain) during low glucose availability (ie during fasting)

https://www.ncbi.nlm.nih.gov/pmc/articl ... 2-0077.pdf
Brain Metabolism during Fasting
Abstract.
Catheterization of cerebral vessels in three obese patients undergoing 5-6 wk of starvation demonstrated that /8-hydroxybutyrate and acetoacetate replaced glucose as the predominant fuel for brain metabolism. A strikingly low respiratory quotient was also observed, suggesting a carboxylation mechanism as a means of disposing of some of the carbon of the consumed substrates.
...snip...
Discussion:
Finally, our subjects failed to show any
deficit on psychometric testing, and electroencephalographic tracings remained unchanged, which suggests that the keto acids did fulfill the predominant energy requirement in a satisfactory fashion.
User avatar
CureOrBust
Family Elder
Posts: 3374
Joined: Wed Jul 27, 2005 2:00 pm
Location: Sydney, Australia

Re: Insulin--Could This Be the Key?

Post by CureOrBust »

lyndacarol wrote:I have not succeeded in decreasing my insulin level; there is no medication to lower the level; there is no "excess insulin therapy"; diet is the only recognized method for reducing the insulin level – nothing has worked for me.
OK, sorry if the following appears antagonistic (you know I mean no aggression :wink: ), however, if you have true conviction that lowering your insulin levels would improve (if not cure your MS) have you not tried total and complete fasting? and I am not talking a single day, and yes it should be performed under medical supervision :!: .
User avatar
CureOrBust
Family Elder
Posts: 3374
Joined: Wed Jul 27, 2005 2:00 pm
Location: Sydney, Australia

Re: Insulin--Could This Be the Key?

Post by CureOrBust »

Reversal of Behavioral and Metabolic Abnormalities, and Insulin Resistance Syndrome, by Dietary Restriction in
Mice Deficient in Brain-Derived Neurotrophic Factor

http://endo.endojournals.org/content/14 ... 6.full.pdf
User avatar
lyndacarol
Family Elder
Posts: 3394
Joined: Thu Dec 22, 2005 3:00 pm
Contact:

Re: Insulin--Could This Be the Key?

Post by lyndacarol »

EXCELLENT information, CureOrBust! The first supports the idea I have read elsewhere: ketone bodies are a perfectly acceptable fuel source for the brain; in fact, I have read ketone bodies are the preferential fuel source for the brain.

CureOrBust wrote:
lyndacarol wrote:I have not succeeded in decreasing my insulin level; there is no medication to lower the level; there is no "excess insulin therapy"; diet is the only recognized method for reducing the insulin level – nothing has worked for me.
OK, sorry if the following appears antagonistic (you know I mean no aggression :wink: ), however, if you have true conviction that lowering your insulin levels would improve (if not cure your MS) have you not tried total and complete fasting? and I am not talking a single day, and yes it should be performed under medical supervision :!: .
AND, for those who may not understand the supportive relationship that CureOrBust and I have, I know that no aggression is intended by the question here. My answer? I have tried complete fasting (having only green tea or water) for a maximum of three days. It is NOT easy – I felt a little dizzy on the third day (because my physician told me that it takes three days to reduce insulin production). Despite your admonition, I did not inform my physician. I returned to regular eating immediately – possibly undoing any long-term improvement in my insulin level. I plan to try it again, but will progress to a ketogenic diet after fasting.

The recent documentary, "Eat, Fast and Live Longer", mentioned Mark Mattson, one of the authors of the Endocrinology Journal article you posted – thank you. I believe his work with insulin resistance syndrome/dietary restriction is extremely important! It spurs me on to try this approach more diligently.
User avatar
CureOrBust
Family Elder
Posts: 3374
Joined: Wed Jul 27, 2005 2:00 pm
Location: Sydney, Australia

Re: Insulin--Could This Be the Key?

Post by CureOrBust »

The documentary, "Eat, Fast and Live Longer" and a lot of the articles appear to attempt to reduce IGF-1 (Insulin like Growth Factor). One of the things that is hard to reconcile, is that I am sure I have read numerous articles that say IGF-1 is good for MS. How do you reconcile this contradiction?

eg: The insulin-like growth factor system in multiple sclerosis.
Abstract wrote:Multiple sclerosis (MS) is a chronic disorder of the central nervous system characterized by inflammation, demyelination, and axonal degeneration. Present therapeutic strategies for MS reduce inflammation and its destructive consequences, but are not effective in the progressive phase of the disease. There is a need for neuroprotective and restorative therapies in MS. Insulin-like growth factor-1 (IGF-1) is of considerable interest because it is not only a potent neuroprotective trophic factor but also a survival factor for cells of the oligodendrocyte lineage and possesses a potent myelinogenic capacity. However, the IGF system is complex and includes not only IGF-1 and IGF-2 and their receptors but also modulating IGF-binding proteins (IGFBPs), of which six have been identified. This chapter provides an overview of the role of the IGF system in the pathophysiology of MS, relevant findings in preclinical models, and discusses the possible use of IGF-1 as a therapeutic agent for MS.
IGF-1 May Give Hope to MS
Recent laboratory experiments on IGF-1 have demonstrated a stimulation of the protective sheath around nerves known as the myelin sheath. In degenerative diseases like multiple sclerosis and ALS or Lou Gehrig’s disease, damage around the sheath stops signals from being transmitted between the brain and nerves.

IGF-1 has been found to regrow these sheaths according to the University of Michigan scientists. Although several growth factors are currently being studied, IGF-1 appears to be most effective at inducing the growth of the sheath and preventing neuronal cell death according to chief researcher Hsin-Lin Cheng. Michigan scientists presented the first results from their experiments with IGF-1 at a conference in New Orleans. The scientists said they removed nerve cells called dorsal root nerves from newborn rats and grew them in a dish. They found that if they stimulated the conditions of diabetes in the dish and then applied the IGF-1 it helped the nerves remain normal.

Tests with IGF-1 are now underway on 40 people with neuropathy at the Mayo Clinic in Rochester, Minnesota. According to these researchers, IGF-1 may provide a new treatment for a whole group of diseases that have not heretofore been treatable.
Sure, the last one is from a whole website promoting IGF-1 :confused:
User avatar
CureOrBust
Family Elder
Posts: 3374
Joined: Wed Jul 27, 2005 2:00 pm
Location: Sydney, Australia

Re: Insulin--Could This Be the Key?

Post by CureOrBust »

PS If you search in google with the following, it should come up with the whole 58 min video on some "Vimeo" site as the first hit.

Google Search

The thing that really caught my attention was the interview with Mark Matteson, at around 46:35 to 46:53, where Mark Matteson's research (on mice) found that the fasting mice developed new neuron growth. :mrgreen:

[edit: may be due to it being based on http://www.google.com.AU]
Last edited by CureOrBust on Sun Apr 28, 2013 4:40 am, edited 1 time in total.
User avatar
NHE
Volunteer Moderator
Posts: 6221
Joined: Sat Nov 20, 2004 3:00 pm
Contact:

Re: Insulin--Could This Be the Key?

Post by NHE »

Your Google search didn't work for some reason. However, you can watch the video on PBS's site.

http://video.pbs.org/video/2363162206
User avatar
lyndacarol
Family Elder
Posts: 3394
Joined: Thu Dec 22, 2005 3:00 pm
Contact:

Re: Insulin--Could This Be the Key?

Post by lyndacarol »

CureOrBust wrote:The documentary, "Eat, Fast and Live Longer" and a lot of the articles appear to attempt to reduce IGF-1 (Insulin like Growth Factor). One of the things that is hard to reconcile, is that I am sure I have read numerous articles that say IGF-1 is good for MS. How do you reconcile this contradiction?

eg: The insulin-like growth factor system in multiple sclerosis.
Abstract wrote:Multiple sclerosis (MS) is a chronic disorder of the central nervous system characterized by inflammation, demyelination, and axonal degeneration. Present therapeutic strategies for MS reduce inflammation and its destructive consequences, but are not effective in the progressive phase of the disease. There is a need for neuroprotective and restorative therapies in MS. Insulin-like growth factor-1 (IGF-1) is of considerable interest because it is not only a potent neuroprotective trophic factor but also a survival factor for cells of the oligodendrocyte lineage and possesses a potent myelinogenic capacity. However, the IGF system is complex and includes not only IGF-1 and IGF-2 and their receptors but also modulating IGF-binding proteins (IGFBPs), of which six have been identified. This chapter provides an overview of the role of the IGF system in the pathophysiology of MS, relevant findings in preclinical models, and discusses the possible use of IGF-1 as a therapeutic agent for MS.
IGF-1 May Give Hope to MS
Recent laboratory experiments on IGF-1 have demonstrated a stimulation of the protective sheath around nerves known as the myelin sheath. In degenerative diseases like multiple sclerosis and ALS or Lou Gehrig’s disease, damage around the sheath stops signals from being transmitted between the brain and nerves.

IGF-1 has been found to regrow these sheaths according to the University of Michigan scientists. Although several growth factors are currently being studied, IGF-1 appears to be most effective at inducing the growth of the sheath and preventing neuronal cell death according to chief researcher Hsin-Lin Cheng. Michigan scientists presented the first results from their experiments with IGF-1 at a conference in New Orleans. The scientists said they removed nerve cells called dorsal root nerves from newborn rats and grew them in a dish. They found that if they stimulated the conditions of diabetes in the dish and then applied the IGF-1 it helped the nerves remain normal.

Tests with IGF-1 are now underway on 40 people with neuropathy at the Mayo Clinic in Rochester, Minnesota. According to these researchers, IGF-1 may provide a new treatment for a whole group of diseases that have not heretofore been treatable.
Sure, the last one is from a whole website promoting IGF-1 :confused:
I cannot reconcile the contradiction, but I can't discount this article in Momentum magazine (NMSS application). It belongs here for its mention that IGF-1 actually worsened MS:

This idea was expressed (page 67) in the Winter 08-09 issue of the MS Society publication named Momentum; it does refer to earlier "success in promoting myelin formation." Of course, that poor mouse! BUT which abstract fits people?…
The growth factor IGF-1 had shown some success in promoting myelin formation, so a Society-funded team led by Stephane Genoud, PhD (The Salk Institute, La Jolla, Calif.), injected it into mice with EAE. The injections actually worsened the disease. (Journal of Neuroimmunology 2005; 168:40-5) Such failures are important to pinpoint before they affect people with MS in clinical trials.
Here is the abstract of the work mentioned:


1: J Neuroimmunol. 2005 Nov;168(1-2):40-5. Epub 2005 Aug 24. Links
Targeted expression of IGF-1 in the central nervous system fails to protect mice from experimental autoimmune encephalomyelitis.Genoud S, Maricic I, Kumar V, Gage FH.
Laboratory of Genetics, The Salk Institute, 10010 N Torrey Pines Rd, La Jolla, CA 92037, USA.

Insulin-like growth factor 1 (IGF-1) has been identified as a critical molecule in the induction of myelination in the central nervous system (CNS). Systemic injection of IGF-1 has been shown to have a varied and transiently protective effect on the clinical course of experimental autoimmune encephalomyelitis (EAE). Since systemic IGF-1 can also modulate peripheral immune lymphocytes, we examined whether a sustained and local delivery of IGF-1 into the spinal cord would have any influence on the chronic course of EAE in C57/BL6 mice. The capability of adeno-associated virus (AAV) to be retrogradely transported efficiently from muscle to motor neurons of the spinal cord was used to overcome the difficulty routinely encountered when attempting chronic delivery of molecules into the CNS. We demonstrate that AAV-mediated delivery of IGF-1 in CNS did not have any beneficial effect on the clinical course of EAE. Injection of AAV-IGF1 after induction of the disease worsened the clinical symptoms. Furthermore, CNS expression of IGF-1 did not affect the pathogenic anti-MOG T cell response, as examined by proliferation and cytokine secretion. Thus, enhanced expression of IGF-1 in the CNS during inflammation does not have a significant effect on myelination. These data have important implications for the potential use of IGF-1 in the treatment of multiple sclerosis.

PMID: 16120466 [PubMed - indexed for MEDLINE]

_________________

Fundamentally, I think the IGF-1 IS worsening people's MS. Does anyone have the results of the Mayo Clinic test of IGF-1 mentioned above: "Tests with IGF-1 are now underway on 40 people with neuropathy at the Mayo Clinic in Rochester, Minnesota."?
Last edited by lyndacarol on Sun Apr 28, 2013 12:11 pm, edited 1 time in total.
PointsNorth
Family Elder
Posts: 683
Joined: Mon Sep 04, 2006 2:00 pm
Location: LeftCoast Canada
Contact:

Re: Insulin--Could This Be the Key?

Post by PointsNorth »

I've found that when I've missed a meal I get symptom improvement. I would like to try the feed/fast cycle. Maybe fast on Monday-Wed-Fri and feed the rest of the week?

Thx for the links NHE and lynda.
Albany 2010. Brooklyn 2011
Hayes inspired Calcitriol+D3 2013-2014
Coimbra Protocol 2014-16
DrG B12 Transdermal Spray 2014-16
Progesterone 2015-16
Low-Dose Immunotherapy 2015-16
My Current Regimen http://www.thisisms.com/forum/regimens-f22/topic25634.html
User avatar
CureOrBust
Family Elder
Posts: 3374
Joined: Wed Jul 27, 2005 2:00 pm
Location: Sydney, Australia

Re: Insulin--Could This Be the Key?

Post by CureOrBust »

PointsNorth wrote:I've found that when I've missed a meal I get symptom improvement. I would like to try the feed/fast cycle. Maybe fast on Monday-Wed-Fri and feed the rest of the week?
When I was at my worst (first diagnosed and on Rebif), I noticed that after eating lunch, I would be a little worse off. But, that may not be directly because of insulin.

As for your plans to fast, three days a week is pretty severe. From the Doco earlier linked, Mark Matteson was suggesting a 5:2 pattern; ie 2 days of fast (<600cal), and 5 days of feast a week. I did a single day of fast on Saturday, and it made Sunday a struggle, not to mention how difficult Saturday was in regards to hunger. However, I took it to the extreme, in more ways than one. I ate 0 calories, and only drank filtered water when I was hungry, which was often. In addition to 0 calories, I also exercised in the morning for 20min on a cross trainer (on high resistance considering), which would of expended a lot if not all the sugars from my blood.

Sunday was tough, maybe today was a little better than Friday, or not. Tomorrow, if I get a chance, I will buy some instant soup in a cup like he used in the doco, and try a 600 cal or less day. In the doco, the docs got him to try it for a few weeks.
CaveMan
Family Elder
Posts: 101
Joined: Sat Apr 28, 2012 8:11 pm

Re: Insulin--Could This Be the Key?

Post by CaveMan »

I saw that doco a while back, there are multiple ways of doing calorie restriction/Fasting.
I adopted a 20/4 protocol a while back, that is a fasting period of 20 hours (including sleep) and a 4 hour eating window in the evening.
It is important to include a large variety of foods in this eating window as this is the one and only meal time/day.
The other thing to consider is allowing your body plenty of time to adapt, so gradually making breakfast later and later, till it becomes lunch, then making lunch later and later till it becomes dinner.
There are many potential benefits which include improved glucose control which IMO is at the core of many chronic diseases, but the warning is to go slow, real slow, don't get ahead of yourself, many people go too fast feel great for a while then start going downhill, this is because their bodies have not fully adapted and the body has enacted a series of metabolic adjustments to deal with the food restriction and one of those may be downregulating thyroid function.
You should go in with the idea of nudgeing your body in the right direction, not enforcing a strict regimen, your body is in charge and if you push too hard it will counter move, like a true Chess master, and sabotage your process, so keep it slow and comfortable.
I would suggest a minimum of three months, preferably closer to 12 months of eating better and drifting slowly to a 20/4 IF protocol.

Be wary of possible thyroid downregulation, so a metabolic slowdown ("starvation response"), this happens when individuals have not allowed enough time for their body to switch from sugar burning to fat burning as a primary fuel source.
It's basically going into the early stages of Ketosis, for a full ketogenic diet healthy individuals can switch over in 2-3 weeks generally, with a small dose of "low carb flu", but those with significant metabolic dysfunction may take 12 months or more, if the body is not allowed adequate time for healing and adjustment then you may find yourself in a worse place than you started at.

Insulin control of blood glucose is very crude and poor as that was never it's primary role to control maximum glucose levels, whereas we have multiple systems and hormones for managing low blood glucose very precisely, this suggests we were never really designed to consume a high carbohydrate diet daily in every meal.
I think when we are properly tuned our bodies are quite capable of managing seasonal and opportunistic carb binges, but these should be the exception rather than the norm.

Once Insulin & Glucose are under control and the inflamatory threats like Omega 6 PUFA's are removed then Leptin levels also begin to recede, Leptin is likely the first hormone dysregulated, many years before Insulin or high blood glucose appears.
I am just an interested individual trying to crack the autoimmune nut.
Partner has Graves Disease, 5 years, showing good test results, looking forward to potential remission in the near future.
3 friends have MS, 1 just recently diagnosed, severity 7/10.
User avatar
Leonard
Family Elder
Posts: 1063
Joined: Fri Dec 18, 2009 3:00 pm
Location: Brussels

Re: Insulin--Could This Be the Key?

Post by Leonard »

CaveMan wrote:Insulin control of blood glucose is very crude and poor as that was never it's primary role to control maximum glucose levels, whereas we have multiple systems and hormones for managing low blood glucose very precisely, this suggests we were never really designed to consume a high carbohydrate diet daily in every meal.
I think when we are properly tuned our bodies are quite capable of managing seasonal and opportunistic carb binges, but these should be the exception rather than the norm.

Once Insulin & Glucose are under control and the inflamatory threats like Omega 6 PUFA's are removed then Leptin levels also begin to recede, Leptin is likely the first hormone dysregulated, many years before Insulin or high blood glucose appears.
@Caveman, we think alike. MS stands for Metabolic Syndrome, a dysregulated metabolism; the sclerosis in our brains are just symptoms on the fringes... our consciousness is located between our ears , but our biological center is the gut. the gut microbiota makes who we are, biologically...

insulin sensitivity is key. and perhaps, with Caveman, the leptin regulation. this is determined by the gut microbiota. there are only a few "bloodgroups"/dominant enterotypes. hunger, fasting etc will influence the microbiota; extreme low calory diet for 6 weeks can even heal diabetes. and as we know, feces transplantation is a real option, and is becoming ever more real for me..

I invite all to look at this presentation: http://www.cvgk.nl/legacy/bestanden/cvc ... rp-def.pdf
Anonymoose
Family Elder
Posts: 1190
Joined: Tue Oct 09, 2012 6:33 am

Re: Insulin--Could This Be the Key?

Post by Anonymoose »

Hi Lyndacarol,

I was wondering if you could post a summary of things you have tried to do to lower your insulin resistance. What has helped? What hasn't helped? Do you have test results to document progress or lack thereof or are you just working from a symptom perspective (I certainly do :) )? Does your resistance decrease when you somehow partially address immune factors (this might be accomplished by raising vitamin d levels)?

Are you going to try the fasting thing again? That would be interesting to observe but not pleasant for you (unless you experience significant improvements).

It seems like proving a causal relationship between insulin resistance and MS can only be done by getting the resistance under control and seeing what happens to MS. It's mind-boggling that you've tried so many things that should help with insulin resistance, yet, as far as I know, you've still not been able to correct it. Maybe it's a downstream component of the MS cascade and you need to go upstream to have an impact??

Just trying to wrap my head around this concept in the context of your experience. I agree that it likely contributes to the MS picture in some people but I wonder if it is truly the cause of (some) MS. In search of the ever-elusive answers...
CaveMan
Family Elder
Posts: 101
Joined: Sat Apr 28, 2012 8:11 pm

Re: Insulin--Could This Be the Key?

Post by CaveMan »

This paper may be worth a read, not specifically MS, but does talk about ancestral diets and the impacts of changes in microbiota composition with modern diets.
The primary distinction being the consumption of grains, flour, processed sugars being Acellular carbohydrates where as traditional diets that were high in carbohydrate consumed cellular carbohydrates like fruit, nuts & starchy tubers.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402009/
I am just an interested individual trying to crack the autoimmune nut.
Partner has Graves Disease, 5 years, showing good test results, looking forward to potential remission in the near future.
3 friends have MS, 1 just recently diagnosed, severity 7/10.
Anonymoose
Family Elder
Posts: 1190
Joined: Tue Oct 09, 2012 6:33 am

Re: Insulin--Could This Be the Key?

Post by Anonymoose »

Thanks caveman. How does that jive with reversal of type 2 diabetes via a vegan/modern diet, presumedly rich in nuts, grains, and legumes? Even if it is the result of lower caloric and fat intake, it still includes the "guilty" foods outlined in the study you referenced. This study doesn't document reversal, I recall hearing a lot about it in recent years but haven't time to find a documenting at the moment. It does speak to some insulin related issues though.
http://www.ncbi.nlm.nih.gov/m/pubmed/19339401/
So much conflicting info!
Post Reply

Return to “General Discussion”