A new concept and treatment options for MS

If it's on your mind and it has to do with multiple sclerosis in any way, post it here.

Postby jimmylegs » Thu Apr 28, 2011 1:18 pm

Hepatic zinc in hemochromatosis.
http://www.ncbi.nlm.nih.gov/pubmed/2040101
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"intensive" therapy

Postby willowford » Thu Apr 28, 2011 5:18 pm

jimmylegs wrote:okay here's why i opened this topic today: interesting points on CBC radio, white coat black art. the topic was overdiagnosis and the guest was saying that managing diabetics by tryig to get them looking 'normal' had resulted in higher mortality. i went looking for the study and it's called 'accord'. turns out they were specifically managing glucose, which made me think of this topic. so here's some info about glucose management.

http://www.diabetesincontrol.com/index. ... le&id=5516
Accord Study Stops Intensive Diabetes Management Due To Increase in Deaths. Treating to normal blood sugars may cause an increase in death.

Effects of Intensive Glucose Lowering in Type 2 Diabetes
The Action to Control Cardiovascular Risk in Diabetes Study Group
http://www.nejm.org/doi/full/10.1056/NEJMoa0802743
Background
Epidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors.

Methods
In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up.

i'm curious what form the intensive therapy took.. no time to investigate further right now though.


Hey Jimmylegs,
There has been MANY of these types of studies. a lot of diabetes funds go towards lowering HbA1c because it is well established that this lowers the risk of heart disease (because that's the big issue with diabetes, the symptoms themselves are often not as debilitating as MS or other disease - the risk of heart attacks is the problem). Intensive (or aggressive) therapy basically means lowering that HbA1c to a level that is known (from previous studies) to have lower risk of adverse outcomes (mostly heart related). Basically, metformin as you know is the first line care (type 2 only), then (if still blood glucose is high) other agents can be added (there are several classes - won't bore you with details cause this isn't a diabetes forum - but there are at least 3 classes out there now, each having at least 2 different drug types to choose from depending on the patient). THEN if even that is not enough (blood glucose still high), they'll have to start receiving insulin. This is actually the case with some type 2 diabetes patients as they get older - even if they're blood glucose was well controlled with meds all their life, over time the pancreas are unable to sustain insulin release, causing hypoinsulinemia - at this time, metformin/other meds do basically nothing - cause of the insulin deficiency - so insulin injections are then the only option.

Hope this helps (and is not too detailed for your original question).
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Postby Leonard » Fri Apr 29, 2011 10:39 am

It is well known that Vitamin D helps suppress the inflammation by the immune system. I believe the same is true for cortisol.

I wonder, and this is also in earlier post in this thread, whether this line of reasoning is conceptually correct. It could well be the other way around.

What do I mean with this: With higher intra-cellular vitamin D levels, the insulin works better and therefore improves the absorption of glucose. As a result, the entire nutritional condition of the cells will improve. And consequently, the inflammation will reduce or the immune system be put to rest. Then we do not speak of suppression (as a pro-action of the vitamin D) but a calming down / put to rest (as a reaction to a better nutritional condition).

More or less the same story could be set up for cortisol. From wikipedia: Its primary functions are to increase blood sugar through gluconeogenesis, suppress the immune system; .. Again, it is perhaps conceptually incorrectly to see the suppression while extra cortisol will improve the nutritional situation of the cells as a reaction of which the immune system calms down. Again, no pro-active suppression by cortisol, but a reaction due to an improved nutritional condition of the cells.

If the latter is conceptually correct, this would be a direct confirmation of the low glucose hypothesis. The very deep - almost dogmatic believe - in the medical world about the concept of suppression (it looks like a doctrine) may stand in the way of a healthy view about what is really going on out there in our micro-cosmos. I think we come close to really solving this thing..
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Postby jimmylegs » Fri Apr 29, 2011 3:52 pm

@willow

your comment about hba1c and heart disease made me decide to search for research on hba1c and magnesium. found this:

Diabetes. 1986 Apr;35(4):459-63.
Magnesium deficiency in IDDM related to level of glycosylated hemoglobin.
Abstract
Magnesium and potassium were analyzed in plasma, erythrocytes, and urine collected during 24 h and in muscle biopsies from 25 subjects with insulin-dependent, type I diabetes mellitus (IDDM). Magnesium was also measured in mononuclear cells. The results were compared with those of 28 healthy controls, and were also correlated with the degree of diabetic control as estimated by analysis of the level of glycosylated hemoglobin (HbA1c). Subjects with IDDM had significantly lower muscle (P less than 0.01) and plasma (P less than 0.001) concentrations of magnesium compared with those of healthy controls. The HbA1c levels correlated significantly with the concentrations of magnesium in muscle (r = -0.62, P less than 0.001), plasma (r = -0.62, P less than 0.001), and mononuclear cells (r = -0.47, P less than 0.05). The results indicate that some patients with IDDM have lowered contents of magnesium in striated muscular and/or plasma, and that those parameters are dependent on the degree of diabetic control.

interesting! and:

http://www.ncbi.nlm.nih.gov/pubmed/21288611

Clin Nutr. 2011 Jan 31. [Epub ahead of print]
Influence of magnesium status and magnesium intake on the blood glucose control in patients with type 2 diabetes.
Abstract
BACKGROUND & AIMS: This study was undertaken to assess magnesium intake and magnesium status in patients with type 2 diabetes, and to identify the parameters that best predict alterations in fasting glucose and plasma magnesium.
METHODS: A cross-sectional study was carried out in patients with type 2 diabetes (n = 51; 53.6 ± 10.5 y) selected within the inclusion factors, at the University Hospital Onofre Lopes. Magnesium intake was assessed by three 24-h recalls. Urine, plasma and erythrocytes magnesium, fasting and 2-h postprandial glucose, HbA1, microalbuminuria, proteinuria, and serum and urine creatinine were measured.
RESULTS: Mean magnesium intake (9.37 ± 1.76 mmol/d), urine magnesium (2.80 ± 1.51 mmol/d), plasma magnesium (0.71 ± 0.08 mmol/L) and erythrocyte magnesium (1.92 ± 0.23 mmol/L) levels were low. Seventy-seven percent of participants presented one or more magnesium status parameters below the cut-off points of 3.00 mmol/L for urine, 0.75 mmol/L for plasma and 1.65 mmol/L for erythrocytes. Subjects presented poor blood glucose control with fasting glucose of 8.1 ± 3.7 mmol/L, 2-h postprandial glucose of 11.1 ± 5.1 mmol/L, and HbA1 of 11.4 ± 3.0%. The parameters that influenced fasting glucose were urine, plasma and dietary magnesium, while plasma magnesium was influenced by creatinine clearance.

CONCLUSIONS: Magnesium status was influenced by kidney depuration and was altered in patients with type 2 diabetes, and magnesium showed to play an important role in blood glucose control.
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Postby Leonard » Fri Apr 29, 2011 11:21 pm

@jimmylegs: is very interesting, thank you!
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Postby Leonard » Sun May 01, 2011 2:51 am

this paper is also very interesting from a conceptual point of view:

http://www.ncbi.nlm.nih.gov/pubmed/20865368

Convergence of metabolic and immune signaling is likely at least partially driven by the evolutionary need during times of food insufficiency to minimize loss of energy to processes that are temporarily nonessential to the survival of the species.

Can we conclude from here: MS is a protective re-action of the species with a perfectly healthy immune system? Incidently this is something Zamboni suggested already a few years ago.
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Postby Leonard » Sun May 01, 2011 3:02 am

The community as a whole can conceptualise very well. I see this happen in other work areas as well where the old model of research, development and innovation is broken and/or overtaken by the Internet.

In modern development, new fora are set up where the experts meet. Everybody is supposed to represent only his personal opinion (not even the one of his employer) and there is a bottom-up approach.

The Internet allows to communicate and self organise without the need of big (public) institutions. This atomic organisation then coordinates by social mechanisms.

The game changed from best organising (industrial/governmental) support for a certain idea (and also convincing the experts in there) to a much broader social movement that is organised bottom-up. This new form allows for an initiative that starts very small and gets more and more momentum like a grassroots campaign. Or there is an alliance large enough to start the marketing machine, the bloggers and the experts to steer the crowd into a certain direction.

The old model is broken; it will never be restored. It is precisely what Brafman and Beckstrom described in their book The Starfish and the Spider: there is a revolution raging all around us. I have seen it happen in other sectors where the resistance to change was huge and the inertia was enormous with hundreds of billions of capital invested. But it happened. That revolution will also embrace the medical world; there is no escape. Now only our health...
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Postby Leonard » Sun May 01, 2011 11:39 am

jimmylegs wrote: CONCLUSIONS: Magnesium status was influenced by kidney depuration and was altered in patients with type 2 diabetes, and magnesium showed to play an important role in blood glucose control.


Magnesium apparently is also important to maintain the right balance of minerals sodium, pottassium and calcium; and therefore for the proper operation of the ion pump and therefore for our motor functions.

Could it be that somehow all these things are connected in one way or the other? in a way that we have not seen yet?
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Postby jimmylegs » Sun May 01, 2011 12:10 pm

or maybe one that we have seen?

“Let food be thy medicine…” Hippocrates
http://www.bmj.com/content/328/7433/0.8.full

...quoting Hippocrates: “Let food be thy medicine and medicine be thy food” (p 211). Although many patients are convinced of the importance of food in both causing and relieving their problems, many doctors' knowledge of nutrition is rudimentary. Most feel much more comfortable with drugs than foods, and the “food as medicine” philosophy of Hippocrates has been largely neglected. That may be about to change. Concern about obesity is rocketing up political agendas, and a growing interest in the science of functional foods is opening up many therapeutic possibilities (p 180).
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Postby Leonard » Mon May 02, 2011 1:52 am

jimmylegs wrote:or maybe one that we have seen?

“Let food be thy medicine…” Hippocrates
http://www.bmj.com/content/328/7433/0.8.full

...quoting Hippocrates: “Let food be thy medicine and medicine be thy food” (p 211). Although many patients are convinced of the importance of food in both causing and relieving their problems, many doctors' knowledge of nutrition is rudimentary. Most feel much more comfortable with drugs than foods, and the “food as medicine” philosophy of Hippocrates has been largely neglected. That may be about to change. Concern about obesity is rocketing up political agendas, and a growing interest in the science of functional foods is opening up many therapeutic possibilities (p 180).


Thanks jimmylegs. I think it's probably not quite as simple as that 'let food be thy medicine..'.

What seems impaired is the feeding at the micro-cellular level. Clearly, this might well have some relation to what you eat but I think the issue is probably a bit more complicated than that because there are all sort of glands, hormones, minerals and vitamins involved in the process of micro-cellular feeding and the operation of the mitochondria (the power generators of the cells). And if there are unbalances there you may just eat all the right things but you will not be able to overcome your problem.

A Google search on cell nutrition and immunity reveals a huge amount of literature on the effects of malnutrition on cellular health and impaired immune competence. A variety of conditions may contribute to malnutrition including pancreatic insufficiency, bile duct obstruction, and other liver diseases.

I am not an expert and for me all this is too difficult to understand or simply too much to absorb. But what I take from the papers is that there is ample evidence that nutritional insult to cells contributes to the abnormalities of inflammation. [yes the direction is important here too!!] The effect of malnutrition is not simply to reduce the availability of endogenous stores of nutrients utilized by the host in defence processes; it may lead to increased susceptibility to secondary infection through reduced synthesis of IL-1 and impaired cell-mediated immunity.

Studies then also found that after adequate nutrition was re-instituted, the production of IL-1 returned to normal, and that nutritional support in inflammatory disease (by providing adequate energy and protein to meet endogenous requirements) restored normal cellular function. Therapeutic applications may be possible and in fact be desirable to address any unbalances in the metabolism.

I have said it may times before on this forum: I wish endocrinologists would jump on this train. I think that liberation from venous insufficiency in the neck (ccsvi) and restoring normal bloodflow are very important; but at the same time that in order to fully solve the MS problem the dimension of micro-cellular feeding must be addressed too.
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Postby jimmylegs » Mon May 02, 2011 6:12 am

i didn't read that one in a lot of detail but.. where do you think cell nutrition comes from?
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Postby Leonard » Mon May 02, 2011 9:29 am

jimmylegs wrote:i didn't read that one in a lot of detail but.. where do you think cell nutrition comes from?


As this article on TIMS suggests http://www.thisisms.com/article181.html sex hormones play a role in MS. Women may also have a more violent hormonal imbalance. Here the explanation may be found why MS occurs twice as much in women than in men.

But there are other hormones which may play a role too. For instance, the adrenal gland is responsible for the cortisol production which is important to increase the blood sugar through gluconeogenesis. The pancreas produces the insulin necessary for the absorption of glucose; and here is the diabetes link. Also the regulation of the insulin may be important. Deficiencies may not necessarily be revealed by the standard 2 hours fast serum insulin test but may need more time (e.g. insulin counter-regulation seen in multiple sclerosis http://www.ncbi.nlm.nih.gov/pubmed/2291833 ). And there may be other hormones involved.

And as we have seen in earlier posts on this thread, the mineral balance is important too. In particular magnesium and zinc seem important to keep the right balance of sodium, potassium and calcium, that in turn seems critical to maintain the equilibrium of the ion pump necessary for our motor functions. Furthermore magnesium seems important because of its role in the blood sugar metabolism
http://www.ncbi.nlm.nih.gov/pubmed/21288611 (thanks jimmylegs)
http://www.livestrong.com/article/36166 ... diabetics/

And Vitamines may play an important role too. As I have understood it, the Vitamines B3, B6 and B12 end up in the final stage as CoQ10, so these would seem important to ensure the power generator of the mitochondria can function. And I think the ion pump will be connected somehow as well.

As far as I understood, how all these hormones, minerals and vitamins relate to each other is not fully understood. I believe that there is a search ongoing in various countries (Denmark, Canada) on precisely this issue.

So, the nutritional condition of the cells will depend not only on the glucose/sugar intake (I personally take a lot of sugar to keep going.. ) but on a variety of other factors. For instance, cholesterol is necessary for a good function of the adrenal gland, and incidently for the production of Vitamin D from sunlight. Where the Vitamin D is important again for the good working of the insulin. http://www.ncbi.nlm.nih.gov/pubmed/18187309 http://findarticles.com/p/articles/mi_m ... _19913495/
http://endo.endojournals.org/cgi/conten ... t/119/1/84 .
(It is known that many MS patients suffer from exhaust of the adrenal gland and Vitamin D shortage).

In our modern society, we have been taught that high cholesterol is bad. That we all need to use unsaturated fats on a vegetal basis. But what happened? People with heart diseases and obesities have increased exponentially. In Japan for instance, people think different and high cholesterol is seen there as a healthy condition. To this end, I often ask myself the question whether – after having been liberated from ccsvi – I should switch from a low fat diet (which was good when I had the serious stenoses in the neck) to take more saturated fats to get the hormone balance right.

As I said, I think we need the endocrinologists to jump on this train.
Last edited by Leonard on Mon May 02, 2011 12:12 pm, edited 2 times in total.
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Postby jimmylegs » Mon May 02, 2011 10:51 am

i am aware that hormones can play a role, and at the same time i am pretty sure that the expression of hormones also can be optimal or otherwise depending on nutritional status.

for example zinc does great things for various issues seen in ms. it also boosts testosterone levels. i can feel the hormone balance change when my zinc levels are up. it's very interesting.
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Postby Leonard » Tue May 03, 2011 1:28 am

your adrenal glands or possible adrenal fatigue being the root of the problem? this website is interesting: http://drlensblog.com/?p=1458

recognise this? well I do ..
http://www.drrind.com/therapies/metabol ... oms-matrix

I think we really come close now...

MS = ccsvi + hormonal imbalance/adrenal gland malfunction??
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Postby jimmylegs » Tue May 03, 2011 1:36 pm

this is super basic but here ya go anyway

http://www.livestrong.com/article/63550 ... l-fatigue/
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