This Is MS Multiple Sclerosis Knowledge & Support Community

I posted this on another forum a few days ago and got no real definative answers
so I thought I would ask here.
Mabye these questions have been asked before (just havent really learned how to navigate this site yet).

Recently I was told that my B's & D's were extremly low and need to take supplements to bring them up.
For now I blame the new diet (diet is good though) for the low levels but staying open minded
looking for answers.
I eat plenty of meats,seafood & get plenty of sunshine.
And have for many years. probally could eat more salads,fruits & veggies.

And I am going to an MS center next month. I have so many of the symptoms of MS looking to rule it out.

So now I have a few questions.

1) What causes B levels to be so low?
2) What causes D levels to be so low?
3) Can taking supplements mask the reasons why they are so low?
4) How long (wks,mths,yrs) do levels so low start to cause serious problems?
5) Will there be permanent issues/damage caused by such low levels if they have been untreated for many years?

These questions actually stem from my other post.
Any insight or direction to find the answers to the questions would be greatly appreciated.

Rick

it's all about cofactors and antinutrients

zinc is required for adequate systemic response to b and d intakes (for the b's i'm talking b12 in particular. that's what I've seen specifically in research. i'd have to go looking for more studies in order to back up the zinc link to any other b vits.

zinc is typically low normal in ms and many other illnesses, vs high normal in healthy controls. do you know what I mean if I say correcting my zinc deficiency tripled my dose-response to d3? (update: probably the work i had done on magnesium status was a more important factor in my much improved dose response to vit d3)

you might also be like many other ms patients and require more magnesium to interact w/ b and d vits. again, ms patients are low normal for magnesium, healthy controls high normal.

if you can get serum zinc and serum magnesium tested that could help tell the tale

yes you can do permanent damage from nutrient depletion. while it can take ages to manifest nutrient issues - depending on the individual - it would be a very good idea to expedite fixing the low levels.

Patients with MS (and other autoimmune diseases) are unable to properly metabolize vitamin D and vitamin B12. The inability to properly metabolize vitamin B12 will lead to the inability to properly metabolize vitamin B1. No other B vitamin is more dependent on its fellow B vitamins than B1. If you are deficient in B12, you will not be able to absorb B1. It will be excreted in the urine.
Folate is also dependent on vitamin B12. Deficiency of vitamin B12 will trap folate in a form that is unusable by the body.
Foods high in protein are highest in B3 or niacin, and a great deal of evidence shows MS patients are unable to properly metabolize proteins.

Research shows that the problem with vitamin B12 in MS and other autoimmune diseases is with the "binding and transport". Here are a few MS studies on this.

Multiple sclerosis associated with vitamin B12 deficiency.
Reynolds, E.H., J.C. Linnell, J.E. Faludy. 1991. Arch Neurol. 48(8):808-11.
“…A vitamin B12 binding and/or transport is suspected. The nature of the association of multiple sclerosis and vitamin B12 deficiency is unclear but is likely to be more than coincidental. Further studies of vitamin B12 metabolism, binding, and transport in multiple sclerosis are indicated, as these cases may offer a clue to the understanding of a still mysterious neurologic disorder.”

Vitamin B12 metabolism in multiple sclerosis.
Reynolds, E.H., T Bottiglieri, M. Laundy, R.F. Crellin, S.G. Kirker. 1992. Arch Neurol.
49(6):649-52.
“…Patients with MS had significantly lower serum vitamin B12 levels…than neurological and normal controls…There is a significant association between MS and disturbed vitamin B12 metabolism… The cause of the vitamin B12 disorder and the nature of the overlap with MS deserve further investigation.”

MS patients lack enzymes called "protease". These enzymes are responsible for digesting dietary proteins and for the binding and transport of vitamin B12. Without these enzymes, you will be unable to properly metabolize vitamin B12 and proteins. if you eat proteins, they will end up in your bloodstream and trigger a cascade of negative responses.

In the following study from Mayo College of Medicine the researchers stated that an “array of studies” implicate protease in multiple sclerosis pathogenesis.

The multiple sclerosis degradome: enzymatic cascades in development and progression of central nervous system inflammatory disease.
Scarisbrick IA.
“An array of studies implicate different classes of protease and their endogenous inhibitors in multiple sclerosis (MS) pathogenesis based on expression patterns in MS lesions, sera, and/or cerebrospinal fluid (CSF). Growing evidence exists regarding their mechanistic roles in inflammatory and neurodegenerative aspects of this disease…”

A lack of protease would also lead to arthritis and an inability to properly metabolize vitamin D. Here is some information from my book on this.

Lita Lee, Ph.D., a chemist and enzyme nutritionist, explained the connection to an inability to properly digest proteins, vitamin D metabolism, and arthritis clearly when she wrote: “All forms of arthritis involve abnormal calcium metabolism. Ninety-nine percent of the body calcium is (or should be) in the bones and teeth. The other one percent, found in the blood, is just as important because it is essential in the blood clotting mechanism, muscle and nerve function, vitamin D function, and the function of hormones that control calcium metabolism (called parathyroid hormones). Of the one percent of calcium in the blood, half is protein-bound and half is ionized. Both require adequate protein digestion. If you are deficient in protein because you can’t digest it, you cannot carry protein-bound calcium. If you lack optimum acidity from inadequate digestion of protein, you will not have enough ionized calcium. In either case, you are a candidate for arthritis.
The abnormal deposit of calcium is one of the factors involved in arthritis and arthritic inflammation. Soft tissue, any kind of body tissue other than bones and teeth, is a target for depositing calcium. Wherever this happens, pathology occurs: in the joints, around inflamed areas (osteoarthritis), in the arteries (arteriosclerosis), in the kidneys (kidney stones), in the soft lenses of the eyes (cataracts), in the brain (stroke) and so on” (Lee, 2009).
As Dr. Lee stated, blood-borne calcium is essential for vitamin D function. The inability to carry protein-bound calcium would explain the low levels of vitamin D found in autoimmune disease. Without blood borne calcium, you would not be able to properly metabolize vitamin D. The problem lies in the binding and transport, just as with vitamin B12. In autoimmune disease, taking additional vitamin D or calcium in supplement form, that you are not able to properly metabolize, would just give your body more vitamin D and calcium to deposit in your joints and tissues. It may also lead to another autoimmune disease called sarcoidosis. Sarcoidosis is an inflammatory condition that produces tiny lumps of cells called granulomas in various organs of the body. These granulomas clump together into large or small groups, resulting in organ damage. Dysregulated calcium and vitamin D metabolism are well-recognized features of sarcoidosis.

phew found it, this was driving me crazy not being able to find it

Effect of Zinc Supplementation on Serum Homocysteine in Type 2 Diabetic Patients with Microalbuminuria
"Zinc supplementation reduced serum homocysteine and increased vitamin B12 and folate concentrations in type 2 diabetic patients with microalbuminuria."

Thank you Jimmy Legs and annesse,
Some of it I understand and some of it well not so much,but I get the jist of it.

Another question if it's not too much trouble.
What should I expect when I go for my 1st appt at the MS center with an MS specialist?

I think the cause of the Vit B deficiency is the gut; the vit is insufficiently produced in the gut.
The cause is an unbalanced gut microbiota. This then give problems for mitochondrial health.

The Vit D question is more tricky. Vit D has many functions in the body, in the blood but also in the gut; and its function may vary during different phases of life. I believe that there is a complex regulatory loop that regulates the vit D concentration in the blood, from inactive to active and the reverse path as well. Some MS patients will have a very high 1.25 active D in their blood, regulating down the inactive 25 OH despite sun baths etc ... Supplementation may have some beneficial effects, and can be seen through increased levels in the blood, but perhaps its real function is in the gut where it helps grow natural peptides that help improve gut microbiota functioning...

on balancing gut microflora composition via nutrition

Increased dietary zinc oxide changes the bacterial core and enterobacterial composition in the ileum of piglets
http://animalsci.highwire.org/content/89/8/2430.full
"This study was conducted to investigate the effects of increased dietary ZnO on the bacterial core and enterobacterial composition in the small intestine of piglets that were fed diets containing a total of 124 or 3,042 mg of Zn per kilogram of diet, respectively. ... Increased dietary ZnO led to an increase of less prominent species and, thus, had a major impact on the bacterial composition and diversity in piglets. This effect may help to stabilize the intestinal microbiota in the sensitive postweaning period. ... The dominating L. reuteri was influenced by greater ZnO supplementation, whereas the second most dominant L. amylovorus was not affected. Other lactobacilli, like L. salivarius, L. johnsonii, or L. helveticus, seemed to trade places in rank. The species specific response to ZnO supplementation may indicate different tolerance mechanisms against greater Zn inclusion; however, it could also be a result of interspecies competition. Considering the drastic increase in abundance of Weissella spp. and Leuconostoc spp., bacteriocin production may also have played a role. Like many other LAB, both genera are known to produce bacteriocins active against other LAB (Papathanasopoulos et al., 1997; Srionnual et al., 2007).
Sequences of the Clostridiales order in the bacterial core mainly consisted of Sarcina ventriculi, an acid-tolerant strict anaerobic species, found in the intestinal tract of piglets and other mammals (Crowther, 1971; Vatn et al., 2000; Thanantong et al., 2006). This species seemed to be very sensitive against ZnO or indirect modifications induced by increased dietary ZnO. The fact that S. ventriculi has also been found in the stomach of horses (Husted et al., 2010), lambs, dogs (Vatn et al., 2000), and free-living Colobus monkeys (Owaki et al., 1974), together with its ability to grow at low pH, indicates that this species may be autochthonous to the stomach of mammals.
An interesting result was observed for Enterobacteriaceae. Although not statistically significant, most detected species increased numerically in relative abundance because of increased dietary ZnO. It should be mentioned that sequence data were generated from a PCR using the same concentration of target DNA, and thus, some species with low relative abundance may have fallen below the detection limit because of the high abundance of a few dominant members. Nevertheless, enterobacteria seemingly gained colonization potential by increased dietary ZnO; substantially more enterobacterial species were detected in animals from the high dietary ZnO trial group. This is in agreement with a previous study by Højberg et al. (2005). Furthermore, a survey of Canadian pig farms revealed an increased presence of an enteropathogenic E. coli strain in farms using dietary greater dietary ZnO (Amezcua et al., 2008). Also, an increase in enterobacterial diversity was observed in a study with piglets (Katouli et al., 1999). These results indicate that dietary ZnO causes an enhanced colonization with enterobacteria in the small intestine of piglets. Consequently, the frequently observed diarrhea-reducing effect of ZnO may not be related to direct reducing effects on pathogenic E. coli, but rather to an increase of the enterobacterial group, which would increase competition among enterobacteria."

rick to answer your question about the 1st appt, I suspect there will be not much about nutrients or gut flora

Hi Rick~I just wanted to make a few more points on vitamin B12 and D, and these missing enzymes, which might be helpful as you search for a cause of your illness.

First-a lack of vitamin B12 and D would result from these missing enzymes (protease and DNase1) Since I believe the evidence shows that all autoimmune diseases originate with these enzymes, you would expect to see the exact same symptoms and findings in any systemic autoimmune disease as you see in MS. Your "diagnosis" will be based on your most current severe manifesting symptom, or on the severity of the disease process as determined by bloodwork, MRI etc.

Remember, according to Mayo College of Medicine, "numerous studies have implicated protease in MS."

Now, take another autoimmune disease, such as Sjogens syndrome (dry eyes and mouth). Sjogens patients also lack these enzymes. Since these enzymes are necessary to bind and transport vitamin B12 and to carry protein-bound calcium, which is essential for proper vitamin D metabolism, you would expect Sjogrens patients to also lack vitamin B12 and D, just as MS patients do.

Here is a study on the B12.
Iron and vitamin deficiencies, endocrine and immune status in patients with primary Sjögren’s syndrome.
Lundström, I.M., F.D. Lindström. 2001. Oral Dis. 7(3):144-9.

“…In total, current or previously treated iron and vitamin deficiencies were registered for 63% of the 1st degree SS patients (iron 51%, vitamin B12 25%...thyroid disease was found in a total of 33% and 30% had had autoimmune thyroiditis… Rheumatoid factor (RF) was detected in 85%...”

Here is the info on the vitamin D.

http://www.lef.org/news/LefDailyNews.ht ... n=VITAMINS
Recent findings seem to show that low vitamin D levels in patients with SS could be associated with severe complications such as lymphoma and peripheral neuropathy. According to the news reporters, the research concluded: "Vitamin D supplementation may be an additional tool for optimization of SS treatment."

For more information on this research see: Novel aspects of Sjogren's syndrome in 2012. Bmc Medicine, 2013;11():93. (BioMed Central - http://www.biomedcentral.com/; Bmc Medicine - http://www.biomedcentral.com/bmcmed/)

Low vitamin B12 will lead to "white matter lesions" since vitamin B12 is necessary to maintain myelin. You would therefore expect to find white matter lesions in Sjogrens on par with those found in MS. The following study confirms that this is the case.

In the following study when fifty-eight Sjögren syndrome (SS) patients with neurologic manifestations associated with SS had magnetic resonance imaging (MRI) of the brain, the researchers found that 70% of the patients had white matter lesions and 40% met the radiologic criteria for MS.


Medicine (Baltimore). 2004 Sep;83(5):280-91.
Neurologic manifestations in primary Sjögren syndrome: a study of 82 patients.
Delalande S, de Seze J, Fauchais AL, Hachulla E, Stojkovic T, Ferriby D, Dubucquoi S, Pruvo JP, Vermersch P, Hatron PY.
Department of Neurology, CHRU Lille France
“…We retrospectively studied 82 patients (65 women and 17 men) with neurologic manifestations associated with primary SS, as defined by the 2002 American-European criteria…Thirty-three patients had brain involvement and 13 patients had optic neuropathy. The disease mimicked relapsing-remitting multiple sclerosis (MS) in 10 patients and primary progressive MS in 13 patients… Thirty percent of patients (all with CNS involvement) had oligoclonal bands… Fifty-eight patients had magnetic resonance imaging (MRI) of the brain. Of these, 70% presented white matter lesions and 40% met the radiologic criteria for MS…”

You would also expect to find evidence of these missing enzymes in Sjogrens.

In the following study the researchers identified subclinical exocrine pancreatic insufficiency in not only Sjögren’s syndrome, but in rheumatoid arthritis (RA) patients as
well. In the Sjögren’s patients tested, 58.3% had a “significant decrease” in pancreatic enzymes. [The exocrine pancreas is where DNase1 and protease originate]

Pancreatic duct antibodies and subclinical insufficiency of the exocrine pancreas in Sjögren’s syndrome.

D’Ambrosi, A., A. Verzola, P. Buldrini, C. Vavalle, S. Panareo, S. Gatto, R. La Corte, L.
Vicentini, A. Boccafogli, R. Scolozzi. 1998. Recenti Prog Med 89(10):504-9.

“In previous studies we reported evidence of subclinical exocrine pancreatic insufficiency in primary or secondary Sjögren’s syndrome (SSI, SSII) and rheumatoid arthritis (RA)…test results, compared to controls, showed a statistically significant decrease in duodenal juice volumes, bicarbonates and enzymes in 58.3% of SSI, and in 30% of RA…”

In an additional study entitled “Exocrine pancreatic function in Sjögren’s syndrome” the researchers concluded, “Exocrine pancreatic impairment was found to be present in 63% of the patients” (Coll, 1989).

You can do this with every autoimmune disease. They are all connected to the exact same disease pathway.

linking back to the topic of protease deficiency from the other thread in which we recently were posting on this subject:
http://www.thisisms.com/forum/general-d ... 22430.html

jimmylegs wrote:I think we have to consider primary zinc deficiency as well, not just secondary. poor zinc status could affect the expression of relevant genes and protease activity
Large doses of zinc oxide increases the activity of hydrolases in rats.
http://www.ncbi.nlm.nih.gov/pubmed/15068813
"ZnO supplementation dose dependently increased the plasma Zn concentration and significantly increased amylase, lipase, trypsin and total protease activity in pancreatic homogenates and small intestinal contents."
...there are diverse explanations for the lower zinc status seen in many ms patients. in my case it was a long history of veganism. I had quite seriously deficient zinc status, and there wasn't much in the way of protein going on either.
question re histidine. "The essential amino acid histidine (which MS patients lack)" can you provide a research link for this statement? I wouldn't mind checking that out. on reading that the foods highest in histidine include beef, turkey, lamb, chicken, and so on, I wouldn't be surprised if I was low in this essential amino acid upon diagnosis!

annesse wrote:Transdermal histamine in multiple sclerosis, part two: A proposed theoretical basis for its use.
“…Here we include preliminary findings on the impairments of digestion and assimilation in MS patients seen in a private clinic. Although only a small number of patients was surveyed, an association was found between impaired gastric acid production, impaired protein hydrolysis, and subnormal plasma histidine levels in patients with MS."

jimmylegs wrote:Here is an additional study on zinc and histidine.
Effects of amino acids on zinc transport in rat erythrocytes.
S P Aiken, N M Horn, and N R Saunders
“A significant proportion of plasma zinc exists complexed with amino acids… [*if* the zinc is there to begin with] These properties suggest that zinc is being transported as a zinc-histidine complex, utilizing an amino acid carrier system…”

perhaps it's a bit more of a two way street re transport and the missing zinc piece is part of the reason histidine levels (and protease levels in general) are lower in ms patients.

Wow thanks for all that,
No matter the out come at the MS center I will need to get involved with vitamins and a healthier diet
so I dont end up with more problems than I have now.

which is better than over analizing my situation and looking for an answer
that can only be answered by the specialists.

Rick

sounds like a good plan all round, rick