B12 insufficiency/MS

[lyndacarol]

From the Journal of Agricultural and Food Chemistry, (January 19, 1998) comes the idea that microwaving partially destroys the B12 in milk and meats: http://pubs.acs.org/doi/abs/10.1021/jf970670x

Effects of Microwave Heating on the Loss of Vitamin B12 in Foods

Fumio Watanabe, Katsuo Abe, Tomoyuki Fujita, Mashahiro Goto, Miki Hiemori, and Yoshihisa Nakano
Department of Food and Nutrition, Kochi Women's University, Kochi 780, Japan, and Department of Applied Biological Chemistry, Osaka Prefecture University, Sakai 593, Japan

J. Agric. Food Chem., 1998, 46 (1), pp 206–210
DOI: 10.1021/jf970670x
Publication Date (Web): January 19, 1998
Copyright © 1998 American Chemical Society

Abstract
To clarify the effects of microwave heating on the loss of vitamin B12 in foods, raw beef, pork, and milk were treated by microwave heating and then their vitamin B12 contents were determined according to a chemiluminescent vitamin B12 assay with hog intrinsic factor. Appreciable loss (∼30−40%) of vitamin B12 occurred in the foods during microwave heating due to the degradation of vitamin B12 molecule by microwave heating. When hydroxo vitamin B12, which predominates in foods, was treated by microwave heating and then analyzed by silica gel 60 thin layer chromatography, two vitamin B12 degradation products were found. One of the compounds with a Rf of 0.16 was purified and partially characterized. The vitamin B12 degradation product did not show any biological activity in the growth of a vitamin B12 requiring microorganism, Euglena gracilis Z, and was not bound to hog intrinsic factor, a mammalian vitamin B12 binding protein. Intravenous administration of the compound (1 μg/day) for 7 days to rats showed that the compound neither has toxicity nor acts as a vitamin B12 antagonist in mammals. These results indicate that the conversion of vitamin B12 to the inactive vitamin B12 degradation products occurs in foods during microwave heating.

Or if you prefer, from PubMed: http://www.ncbi.nlm.nih.gov/pubmed/?term=10554220

[NHE]

Hyperhomocysteinemia is associated with cognitive impairment in multiple sclerosis.
J Neurol. 2008 Jan;255(1):64-9.

• Hyperhomocysteinemia (HHcy) has been associated with cognitive impairment in various neurological diseases. Cognitive impairment occurs early in multiple sclerosis (MS). Conflicting data have been reported regarding plasma total homocysteine (tHcy) levels in MS patients, and the impact of HHcy on cognitive impairment in MS is not known. This study investigated whether plasma total homocysteine levels are increased in MS and if HHcy is associated with cognitive impairment in MS. We compared tHcy levels in 94 patients with MS and 53 healthy age-matched controls. We used a neuropsychological test battery that included the Raven's Coloured Progressive Matrices, the Visual Search Test, the Trail Making Test A and B, the Immediate and Delayed Recall of a Short Story, the 30 Paired Word Associates, the Rey-Osterrieth Complex Figure Test, and the Semantic and Verbal Fluency Tests. Clinical (sex, age, type of MS, relapse, disease duration, coexisting disease, smoking habit, and physical disability) and laboratory variables (HHcy, low serum levels of folate and vit.B12, MTHFR genotype) were evaluated for their ability to predict cognitive impairment. The mean tHcy was higher in patients (13.19 micromol/L, SD5.58) than in controls (9.81 micromol/L, SD2.53; p < 0.001). Univariate analysis determined the following factors to be associated with cognitive impairment: higher age at observation, chronic progressive course of disease, longer disease duration,moderate or severe physical disability, and frequency of HHcy. With multivariate regression analysis, there remained a significant association only between frequency of HHcy and cognitive impairment (beta 0.262, p = 0.01). We conclude that tHcy levels are increased in MS and that HHcy is associated with cognitive impairment in this disease.

[NHE]

B12 & homocysteine study in the news...

http://www.bbc.com/news/health-30022534

Taking vitamin B12 and folic acid supplements does not seem to cut the risk of developing dementia in healthy people, say Dutch researchers.

In one of the largest studies to date, there was no difference in memory test scores between those who had taken the supplements for two years and those who were given a placebo.

The research was published in the journal Neurology.

Alzheimer's Research UK said longer trials were needed to be sure.

B vitamins have been linked to Alzheimer's for some years, and scientists know that higher levels of a body chemical called homocysteine can raise the risk of both strokes and dementia.

Vitamin B12 and folic acid are both known to lower levels of homocysteine.

That, along with studies linking low vitamin B12 and folic acid intake with poor memory, had prompted scientists to view the supplements as a way to ward off dementia.

Yet in the study of almost 3,000 people - with an average age of 74 - who took 400 micrograms of folic acid and 500 micrograms of vitamin B12 or a placebo every day, researchers found no evidence of a protective effect.

All those taking part in the trial had high blood levels of homocysteine, which did drop more in those taking the supplements.

But on four different tests of memory and thinking skills taken at the start and end of the study, there was no beneficial effect of the supplements on performance.

I suggest that the study's negative results were due to the fact that the researchers started the study with patients that had an average age of 74. Perhaps the damage from high homocysteine was already done and lowering it at that point was not preventive. It would be interesting if the study started with patients at a younger age, say 40 or 50, and then followed them for an extended time period. Perhaps reducing homocysteine at a younger age would be more protective against dementia.

[NHE]

Vitamin B12 and folate (aka methylfolate) work together. They are like the two wheels of a bicycle in that you're not going to get very far with only one or the other. To that end, I recommend watching this presentation by Dr. Benjamin Lynch as an introduction to the methylation cycles involving folate and vitamin B12.

[lyndacarol]

"Everything You Want Your Doctor to Know about Vitamin B12"

Once again, I highly recommend this 50-minute documentary featuring Sally M. Pacholok, RN, BSN & her husband Jeffrey J. Stuart, D.O. (authors of the book, Could It Be B12? An Epidemic of Misdiagnoses); Lawrence Solomon, M.D., hematologist with Yale Medical School; Ralph Green, M.D., hematologist at UC Davis; and Donald Jacobsen, PhD, at the Cleveland Clinic (Homocysteine Research Lab).

Apparently, a movie has been made about Sally Pacholok and will be released in January 2015: http://www.imdb.com/title/tt3520022/

Recently, I learned there was an October 2006 BBC documentary "Inside Out" – Dr. Joseph Chandy and B12. Since BBC productions are usually very good, I suspect this documentary would be very informative.

I have been unable to locate the entire documentary, but found this 10-minute video:


Janette first appeared in the BBC InsideOut documentary in October 2006. Since then the NHS has forced her doctor to withdraw B12 replacement therapy on a number of occasions, and she tells of her struggles with having B12 and then having it taken away.

She has bravely agreed to be filmed without her usual wig, but her memory is playing up because it is so long since her last injection.


Is there a way to see the entire BBC documentary? http://www.bbc.co.uk/programmes/article ... inside-out

[lyndacarol]

http://www.ncbi.nlm.nih.gov/pubmed/17921401

Am J Clin Nutr. 2007 Oct;86(4):1187-92.

Proportion of individuals with low serum B12 concentrations without macrocytosis is higher in the post-folic acid fortification period than in the pre-folic acid fortification period.
KF Wyckoff, V Ganji
Rush University Medical Center, Chicago, IL, USA.

Abstract

BACKGROUND:
Large intakes of folic acid may delay the diagnosis of vitamin B-12 deficiency, which could lead to irreversible neuropathy.
OBJECTIVE:
The objective of this study was to determine whether the proportion of individuals with low serum vitamin B-12 without macrocytosis (undiagnosed vitamin B-12 deficiency) has increased in the post-folic acid fortification period.
DESIGN:
Individuals aged >or=19 y with low serum vitamin B-12 (<258 pmol/L) and mean corpuscular volume (MCV) measured between 1995 and 2004 were identified from medical records. The proportion and odds ratios of individuals with low serum vitamin B-12 without macrocytosis by sex, race, and age according to prefortification (n = 86), perifortification (n = 138), and postfortification (n = 409) periods were determined.
RESULTS:
MCV was significantly lower in the postfortification period (88.6 fL) than in the prefortification (94.4 fL; P < 0.001) and perifortification (90.6 fL; P = 0.007) periods. The proportion of subjects with low serum vitamin B-12 without macrocytosis was significantly higher in the postfortification (approximately 87%) and perifortification (approximately 85%) periods than in the prefortification period (approximately 70%; P < 0.001). In a sex-, race-, and age-adjusted analysis, the odds ratio for having low serum vitamin B-12 without macrocytosis was 3.0 (95% CI: 1.7, 5.2) in the postfortification period relative to the prefortification period.
CONCLUSIONS:
Subjects with low serum vitamin B-12 were likely to be without macrocytosis in the postfortification period. MCV should not be used as a marker for vitamin B-12 insufficiency. It is possible that folic acid fortification may have led to a correction of macrocytosis associated with vitamin B-12 insufficiency.

[NHE]

B12 deficiency can sometimes be difficult to diagnose. Roughly 80% of serum B12 is bound to haptocorrin and is inactive. In addition, serum homocysteine can be elevated in B12 deficiency though it's also elevated in the case of folate deficiency so it's not specific to B12. Moreover, high methylmalonic acid (MMA) measurements thought to be specific to low B12 can sometimes give false negatives. This can occur if a patient is taking antibiotics at the time that MMA is tested. The following paper suggest that it may be more accurate to measure holotranscobalamin which is the active form of B12 in the serum.

Cobalamin deficiency.
Subcell Biochem. 2012;56:301-22.

• Cobalamin (Cbl, vitamin B12) consists of a corrinoid structure with cobalt in the centre of the molecule. Neither humans nor animals are able to synthesize this vitamin. Foods of animal source are the only natural source of cobalamin in human diet. There are only two enzymatic reactions in mammalian cells that require cobalamin as cofactor. Methylcobolamin is a cofactor for methionine synthase. The enzyme methylmalonyl-CoA-mutase requires adenosylcobalamin as a cofactor. Therefore, serum concentrations of homocysteine (tHcy) and methylmalonic acid (MMA) will increase in cobalamin deficiency. The cobalamin absorption from diet is a complex process that involves different proteins: haptocorrin, intrinsic factor and transcobalamin (TC). Cobalamin that is bound to TC is called holotranscobalamin (holoTC) which is the metabolically active vitamin B12 fraction. HoloTC consists 6 and 20% of total cobalamin whereas 80% of total serum cobalamin is bound to another binding protein, haptocorrin. Cobalamin deficiency is common worldwide. Cobalamin malabsorption is common in elderly subjects which might explain low vitamin status. Subjects who ingest low amount of cobalamin like vegetarians develop vitamin deficiency. No single parameter can be used to diagnose cobalamin deficiency. Total serum cobalamin is neither sensitive nor it is specific for cobalamin deficiency. This might explain why many deficient subjects would be overlooked by utilizing total cobalamin as status marker. Concentration of holotranscobalamin (holoTC) in serum is an earlier marker that becomes decreased before total serum cobalamin. Concentrations of MMA and tHcy increase in blood of cobalamin deficient subjects. Despite limitations of these markers in patients with renal dysfunction, concentrations of MMA and tHcy are useful functional markers of cobalamin status. The combined use of holoTC and MMA assays may better indicate cobalamin status than either of them. Because Cbl deficiency is a risk factor for neurodegenerative diseases an early diagnosis of a low B12 status is required which should be followed by an effective treatment in order to prevent irreversible damages.

[lyndacarol]

http://teachneuro.blogspot.ca/2011/09/l ... -sign.html

L'hermitte's sign can occur as a result of:

compressive myelopathy
radiation myelopathy
subacute combined degeneration of the spinal cord (vB12 deficiency)
copper deficiency
tumors
etc.

[jimmylegs]

ETC

[Blue2014]

Can anyone tell me how long I should be off of any supplements containing B-12 before getting tested so that my results are not skewed? All of my prior testing was completed while I was taking a multi-vitamin that contained B-6 and B12.

[jimmylegs]

i like to wait for 2 weeks between end of any supplement regimen, and bloodwork. i also do my tests fasting vs random.

[lyndacarol]

http://www.researchgate.net/publication ... _sclerosis

Metabolic Brain Disease
September 2006, Volume 21, Issue 2, pp 117-133

Iron and the folate-vitamin B12-methylation pathway in multiple sclerosis

S.J. van Rensburg, M.J. Kotze, D. Hon, P. Haug, J. Kuyler, M. Hendricks, J. Botha, F.C.V. Potocnik, T. Matsha, R.T. Erasmus

Received: 31 July 2005 / Accepted: 18 November 2005
© Springer Science+Business Media, Inc. 2006

Abstract

Some subjects with multiples sclerosis (MS) present with low blood iron parameters. Anecdotal reports and a single patient study suggest that iron supplementation may be beneficial in these subjects. Myelin is regenerated continually, but prerequisites for this process are iron and a functional folate-vitamin B12-methylation pathway. The aim of this study was to determine iron status, folate and homocysteine in MS subjects, and to evaluate the effect on MS symptoms if deficiencies were addressed. Results: In relapsing-remitting MS subjects, serum iron concentration correlated significant weight with age at diagnosis (r = 0.49; p = 0.008). In Caucasian female MS subjects, serum iron and ferritin concentrations were significantly lower than in matched controls. In a 6-month pilot study, 12 subjects taking a regimen of nutritional supplements designed to promote myelin regeneration, improved significantly neurologically as measured by the Kurtzke EDSS (Total Score means 3.50 to 2.45, 29.9%; p = 0.021). These were significantly improved (p = 0.002) compared to 6 control group patients taking multivitamins (Kurtzke Score increased by 13.9% from 4.83 to 5.50). Both groups had significantly reduced homocysteine concentrations at 6 months, suggesting that methylation is necessary but not sufficient for myelin regeneration.

Introduction

Multiple sclerosis (MS) is a disorder in which autoreactive immune responses are involved in the attack on myelinated axons, thereby interfering with the conduction of signals to the periphery (Steinman, 1993). The disease process is often progressive, leading to chronic disability. The diagnosis of MS is extremely stressful for patients and care-givers alike because at diagnosis neurologists cannot deduce from the severity of the symptoms what the disease outcome will be. After an initial remission, some subjects experience few symptoms for long periods of time, while others deteriorate rapidly. The diagnosis of MS is mainly clinical (Poser and Brinar, 2004), assisted by cerebrospinal fluid analysis (Friedman et al., 2005), while magnetic resonance imaging (MRI) is gaining importance in diagnosis and follow-up (McDonald et al., 2001).

The aetiology of MS is complex and multi-factorial, involving genetic and environmental factors, while a viral component is also implicated (De Villiers et al., 2006). Furthermore, a combination of different factors may cause disease in different patients. Metals have previously been implicated in the aetiology of MS (Clausen, 1993). The role of excess iron has been investigated, but three clinical trials attempting to remove excess iron by chelation with desferrioxamine have been inconclusive (LeVine and Chakrabarty, 2004). A study by Grant et al. (2003) showed that low iron concentrations in food protected mice against developing experimental autoimmune encephalomyelitis (EAE), a mouse model for studying autoimmunity in MS. Contrary to these findings, a single patient study demonstrated stabilisation of the MS disease process with no further degeneration when a patient took iron supplements daily together with other nutrients (Rooney et al., 1999). The role of iron in the aetiology and pathology of MS has thus not been elucidated.

Since myelin regeneration is a prerequisite for remission, it is important to note that iron is indispensable for myelin synthesis. Iron deficiency during early postnatal life as well as in later life, results in a reduced amount of myelin in the spinal cord and white matter of rat pups (Yu et al., 1986; Beard et al., 2003). In mice, the disruption of iron availability, either by limiting dietary iron intake or by altering iron storage capacity, resulted in decreased myelin proteins and lipids (Ortiz et al., 2004). Proteolipid protein was most consistently affected, suggesting that limiting iron to oligodendrocytes results not only in hypomyelination but also in a decrease in myelin compaction, i.e. in the structure of the myelin. Electron microscopic studies have revealed high concentrations of iron in the cytoplasm of oligodendrocytes and within myelin (Connor and Menzies, 1996). Many of the enzymes involved in the biosynthetic pathways that produce myelin utilize iron as part of their catalytic center (LeVine and Chakrabarty, 2004). Myelinogenesis is a highly energy-intensive process resulting in a high metabolic demand for iron. Hulet et al. (1999) found ferritin receptors on oligodendrocytes and suggested that the significance of a cellular ferritin receptor was that ferritin was capable of delivering 2,000 times more iron per mole of protein than transferrin to the oligodendrocytes.

Iron enrichment within both oligodendrocytes and myelin raises the possibility that an imbalance in the management of iron during the disease process could lead to the production of iron-catalyzed free radicals that would cause oxidative damage. Toshniwal and Zarling (1992) found that the inflammation during an acute exacerbation causes so much lipid peroxidation that pentane can be measured in the breath of the patients, but during remission exhaled pentane was similar to values recorded for control subjects.

Vascular damage in MS is implicated in the finding of higher homocysteine levels in MS subjects (Vrethem et al., 2003). Interestingly, iron deficiency may also be linked to increased homocysteine levels. Prolonged iron deficiency anaemia is associated with gastritis and atrophy of glands producing intrinsic factor in the stomach (Davidson and Markson, 1955, 1959). Optimal functioning of the folate-vitamin B12-methyl transfer cycle continuously providing activated methyl groups, is a prerequisite for myelin production and maintenance, and long-term deficiencies of this pathway cause demyelinating diseases of the brain and spinal cord (Selzer et al., 2003). Inborn errors of metabolism involving the genes of the methyl transfer pathway are known to cause inadequate myelination and serious disability from childhood, but supplementation with the chemical metabolite following each metabolic block was found to restore the myelin as well as some of the functional deficiencies (Surtees et al., 1991).

Polymorphisms in the genes of the methyl transfer pathway may occur without having an effect on the phenotype under normal circumstances, but when the substrates or co-factors of this pathway are depleted, demyelination may follow (Selzer et al., 2003). The latter case study illustrates this principle. The authors describe extensive demyelination of the brain and subsequent death of a child after anesthesia with nitrous oxide, which irreversibly oxidizes the cobalt in cobalamine (vitamin B12). The activity of methionine synthase (the enzyme which utilizes cobalamine) is reduced to zero after 2 h of anaesthesia (Selzer et al., 2003). This adverse effect was amplified in the patient by the fact that he had two polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR) which reduced the activity of this enzyme as well, effectively blocking the production of active methyl groups. Importantly, in the deceased patient normal vitamin B12 levels were measured (403 pg/mL) even though the activity of the enzyme was zero, i.e. in this study the vitamin B12 assay did not distinguish between active and inactive (oxidized) vitamin B12. This may explain the results of Vrethem et al. (2003) who found increased homocysteine levels in MS subjects, but without decreased vitamin B12. Other researchers have found decreased levels of vitamin B12 and folic acid in serum and CSF of MS subjects (Reynolds et al., 1992; Frequin et al., 1993; Kolesar, 2000).

The aims of the present open-label pilot study were to determine iron parameters, as well as folate and homocysteine concentrations in a group of MS subjects, and to correct deficiencies while observing possible effects on MS symptoms.

[lyndacarol]

From the article: The conundrum of iron in multiple sclerosis - Time for an individualised approach
Susan J van Rensburg · Maritha J Kotze · Ronald van Toorn ·

"The symptoms of vitamin B12 deficiency may mimic those of MS (Ungley and Campbell 1951); misdiagnosis of MS with consequent disability is particularly tragic in light of the fact that vitamin B12 deficiency is an easily diagnosed and treatable disorder. Objective evidence for improvement is provided by doing the EDSS; differences can already be seen over 3–6 months and can be confirmed over longer periods (Nordvik et al. 2000; van Rensburg et al. 2006). Since MS patients differ it should never be assumed that disease progression is inevitable. "

ABSTRACT: Although the involvement of immune mechanisms in multiple sclerosis (MS) is undisputed, some argue that there is insufficient evidence to support the hypothesis that MS is an autoimmune disease, and that the difference between immune- and autoimmune disease mechanisms has yet to be clearly delineated. Uncertainties surrounding MS disease pathogenesis and the modest efficacy of currently used disease modifying treatments (DMTs) in the prevention of disability, warrant the need to explore other possibilities. It is evident from the literature that people diagnosed with MS differ widely in symptoms and clinical outcome--some patients have a benign disease course over many years without requiring any DMTs. Attempting to include all patients into a single entity is an oversimplification and may obscure important observations with therapeutic consequences. In this review we advocate an individualised approach named Pathology Supported Genetic Testing (PSGT), in which genetic tests are combined with biochemical measurements in order to identify subgroups of patients requiring different treatments. Iron dysregulation in MS is used as an example of how this approach may benefit patients. The theory that iron deposition in the brain contributes to MS pathogenesis has caused uncertainty among patients as to whether they should avoid iron. However, the fact that a subgroup of people diagnosed with MS show clinical improvement when they are on iron supplementation emphasises the importance of individualised therapy, based on genetic and biochemical determinations.
Metabolic Brain Disease 03/2012; 27(3):239-53. DOI:10.1007/s11011-012-9290-1 · 2.64 Impact Factor

[jackD]

I had an interesting experience directly related to the B-12/MS problem.

My doctor an Internist/cardiologist had one of his patients who had suspected she had MS call me to talk about MS.

She had severe TN Trigeminal Neuralgia facial pain for many months and had seen lots of doctors and had all kinds of tests. While we were talking she mentioned she did not eat any meat for religious reasons and had recently gone to a VERY VERY strict NO ANIMAL products diet.

Based on what I had read in this thread in the past I suggested she insist our doctor give her a B-12 shot to see if it could help.

She did it the next day.

Unfortunately I had a visit with him the day after that.

He told me in a rather stern firm tone "I do the diagnosing around here!".

She called me two days later and told me the terrible facial pain was gone.

I also suggested she see a dietician and learn if a healthy diet could be found. I just talked two days ago to her and she has now a diet plan that includes some meat at least once a month plus other animal product choices.

I visited with my doctor yesterday and he thanked me for helping her and that she had stated she held me in high regard.

It had a happy ending for all.

jackD

[NHE]

It's good to hear there was a happy ending. I hope that she continues with the B12 shots. Once neurological symptoms appear due to B12 deficiency, there's not enough B12 found in even a healthy, well rounded diet to correct the deficiency.