VITAMIN B12 DEFICIENCY:
Vitamin B12 is essential for making DNA, forming and maintaining myelin sheaths, making neurotransmitters, and the production of red blood cells.
It is possible to be misdiagnosed with MS when you actually have B12 deficiency, and such a misdiagnosis can be devastating, but researchers have also found that many people with confirmed MS also have low B12. Optimising B12 in the diet, and checking that you are able to properly absorb and metabolise this vitamin can be part of your health optimisation strategy.
This article in the Journal of The Neurological Sciences discusses the difficulties of making a differential diagnosis between B12 deficiency and MS. http://www.direct-ms.org/pdf/NutritionMS/B12%20and%20MS.pdf
Did your doctor test you for B12 deficiency as soon as possible once neurological symptoms became evident, and are they monitoring your B12 status as you age?
In a nutshell:
More detail:
Vitamin B12 deficiency can mimic the symptoms of MS, including lesions found on MRI
B12 deficiency can damage the myelin around the nerve and the nerve itself. Like progressive MS, damage can occur particularly in the spinal cord (Subacute combined degeneration of the spinal cord), and usually affects older adults after the age of 40. Like progressive MS, the neurological damage caused by B12 deficiency is not primarily inflammatory. Any invasion of dead patches of nerves by inflammatory immune cells in the CNS which has been damaged by B12 deficiency would presumably then only be associated with normal bodily ‘clean-up’ processes in the CNS.
Neurological symptoms could include decreased or brisk reflexes, loss of control of the toes and/or feet, loss of the sense of where parts of your body are positioned, foot drop and tripping over your toes, muscle weakness, ataxic gait (an unsteady, uncoordinated walk), weakness, burning, tingling and numbness, L’Hermittes sign (a sudden electric shock – like pain when the head is bent forward) sudden ice-pick pains, incontinence, brain atrophy (shrinkage), optic neuropathy, fatigue, insomnia, tremors and paralysis.
Psychiatric symptoms could include cognitive decline, ‘brain fog’ memory loss, confusion, disorientation, anxiety, depression, disorientation, paranoia, psychoses, schizophrenia, ADHD, and dementia.
B12 deficiency can occur for many reasons, including poor diet, gastro intestinal difficulties in processing food, ageing, metabolism problems, medications, and surgery amongst others
For a person to receive sufficient B12, it must firstly be present in the diet. B12 can only be found in animal products, you cannot obtain it from plants or sunlight. Also, being a water soluble vitamin (not stored in fat) your stocks must be replenished every day. So vegetarians and vegans are two groups who are at obvious risk of B12 deficiency. Additionally, some foods are B12 analogues and can block B12.
B12 is only needed in tiny amounts, but most people who are deficient in B12 eat foods with plenty of vitamins, because the second and third steps of absorption and metabolism are also crucial to getting B12 to where it is needed. Even if you are getting enough B12 in your food, you still have to absorb it and metabolise it properly.
Some of the problems with absorption can be not enough hydrochloric acid or the enzyme pepsin released in the stomach to break the B12 out of food. Dysfunction in the production of intrinsic factor or pancreatic proteases will also reduce the absorption of B12, as will gastrointestinal problems such as ulcerative colitis, Crohn’s disease, atrophic gastritis (inflammation and deterioration of the stomach lining), gastric ulcers, small intestinal bacterial overgrowth (SIBO), intestinal parasites or bacteria such as giardia, or H.pylori infections.
Use of medications such as proton pump inhibitors, antacids, and many others may lead to a deficiency in B12, including steroids and immune modulating drugs which are used to treat MS. A potent drug called Methotrexate which is sometimes used for Multiple Sclerosis, can also be related to B12 deficiency.
Vitamin C supplementation (Ascorbic acid) supplements can reduce the body’s capacity to absorb and utilise B12 and may convert it into biologically unavailable forms.
This article by San Pathology (a service operated by Sydney Adventist Hospital in Sydney Australia) concisely summarises some of the complexities surrounding B12 testing and deficiency, and notes the link between high dose Vitamin C and the destruction of B12 in the body.
http://www.sah.org.au/assets/files/PDFs/Pathology%20PDFs/Vitamin%20B12%20Update_San%20Dr.pdf
Surgery to remove part of the bowel or gastric bypass surgery can also lead to B12 deficiency, as can the use of proton pump inhibitors or antacids which reduce the hydrochloric acid levels, and antibiotics, which can reduce or eradicate populations of bacteria that are essential to the absorption of B12 in the gut. There are many other medicines which can create deficiencies, and the use of nitrous oxide for anaesthesia or recreational use can also cause an acute loss of B12 capacity in the body.
Hypothyroidism will accelerate B12 deficiency, as will low Vitamin B2. Genetic problems (See errors of B12 metabolism) or other metabolic problems may also cause people to be unable to process B12 effectively.
Ageing can be involved in many of these processes, and some authorities warn that anyone over forty is at increased risk of B12 deficiency, and anyone over sixty has up to a 40% risk of having a significant deficiency.
Once a deficiency is in place, it may be very difficult to correct using food alone, and many will require large doses of the correct type of supplements to overcome the deficiency and be monitored for life.
Nitrous oxide (an anaesthetic), inactivates B12 in the body and can cause life threatening harm. People with neurological diseases like MS should consider talking this over with their surgeon and/or anaesthetist, dentist or obstetrician before undergoing anaesthesia where this compound is going to be used, and consider having their B12 levels monitored before and afterwards.
Damage may occur at levels much higher than the lower limit set by pathology labs and Neurological damage may occur years before blood tests become unusual
Pathology lab reference ranges and units of measurement differ around the world and may even vary between pathology labs in the same country. However, reference ranges in your locality may have been set for changes in the blood, not neuropsychiatric change, and may be out of step with best practice in countries where this is recognised.
MTHFR Australia discusses this issue here http://www.mthfrsupport.com.au/vitamin-b12-reference-range-level-set-low/
In Australia, it is difficult to get comprehensive information on lab testing. It appears that total levels of B12 that are circulating in the blood are tested (serum B12) but this may include both active and inactive forms of the vitamin, leading to potentially inaccurately high reporting of levels.
Results are quoted in pmol/L, and one well known Australian lab’s reference range is 135-650 pmol/L. Doctors may therefore consider patients to be ‘normal’ even at the lower reference range, even if neuropsychiatric symptoms are present, and these could begin at levels of around 300 pmol/L (including brain shrinkage). At these lower ranges, there is a grey zone where damage may be occurring but it is ignored or ascribed to another cause that is non-treatable (like 'normal' ageing) or treatable with drugs (such as antidepressants) that do not address the cause. Japan is reported to have raised the lower limit to 500 pmol/L in the 1980’s.
However, steps are being made to improve this. Some lab reports now come with the following advice: “From 1 November 2014, active B12 (holotranscobalomin) testing will be performed on all patients with low or equivocal (up to 260 pmol/L) total B12 results. “ This acknowledges that B12 levels are risky up to 260 pmol/L and that testing for holotranscobalomin at the very least, will give a clearer picture.
A February 2014 Australian Government Department of Health MBS reviews - Vitamin B12 testing report noted that “There is currently no consensus on the best method to estimate vitamin B12 deficiency and vitamin B12 status. A 2011 systematic review … found low levels of test sensitivity and, to a lesser extent, specificity.” There is currently no internationally agreed definition for vitamin B12 deficiency based on clinical manifestations or on the ‘cut-off’ values that are used to define vitamin B12 deficiency, which vary between 120-200 pmol/L.”
Consider: this is a potentially devastating neuropsychiatric condition with a very narrow treatment window to avoid irreversible damage, and an Australian Government Health Department report has found that testing may be insensitive, and that there is no internationally agreed definition for laboratory or clinical B12 deficiency. It appears that doctors may be relying on essentially non-existent guidelines or at best potentially inaccurate or inconsistent guidelines for the diagnosis of this potentially crippling condition in Australia.
The report may be found here;
http://www6.health.gov.au/internet/main/publishing.nsf/Content/7C28F0B6D06F9FFCCA257EB9001D769B/$File/Vitamin%20B12%20testing%20Review%20Report.pdf
B12 deficiency is a complex subject and to fully understand all the biochemical interactions and the impact on the body is a field of study in itself; Your doctor may think of B12 deficiency in terms of changes in your blood that relate to anaemia and not in terms of neuropsychiatric issues. Neuropsychiatric problems may precede blood abnormalities by many years; If you are tested for B12 deficiency your doctor may not have in-depth knowledge of the issue and may instead be guided by pathology lab ranges
The above report notes the lack of an international standard for laboratory and clinical B12 deficiency. A review of the literature on the multiple intricacies involved in the subject will quickly convince the reader of the complexities involved in the clinical apprehension of B12 deficiency, interpreting lab results, diagnosing an outright deficiency or functional deficiency, unravelling causes, appreciating individual biochemical responses, and instituting and monitoring treatment. Entire books have been written on the subject. It is unlikely that general practitioners everywhere will be well acquainted with the topic or be fully aware of the pitfalls. Furthermore your doctor may have been trained to pick up on B12 deficiency in the presence of symptoms of anaemia, but neuropsychiatric symptoms can precede blood changes for many years, and the widespread use of folate fortified foods may mean that these changes are seen less and less, while an underlying B12 deficiency remains.
Jill Benson, writing in the publication Vitamin B12 deficiency - why refugee patients are at high risk notes: “The medical profession has often relied on the presence of megaloblastic anaemia as an indication to check vitamin B12 status. Changes in the blood film with macrocytosis and hypersegmented neutrophils are late manifestations of folate or vitamin B12 deficiency and should not be relied upon as an indication for testing of vitamin B12 levels. In addition, those with a very low vitamin B12 and a normal folate may not have a megaloblastic picture but will still be at risk of developing neuropsychiatric and cardiovascular sequelae. Serum concentrations of vitamin B12 may be low in the presence of normal tissue levels if there is concomitant folate deficiency, pregnancy, iron deficiency or in certain rare inherited disorders of vitamin B12 metabolism. There is no universal agreement on the recommendations for the treatment of vitamin B12 deficiency in those who do not have pernicious anaemia. All patients with vitamin B12 < 220pmol/L should have their H. pylori status ascertained with serum antibodies (if they have not had previous treatment), breath test or stool antigen...”
Your doctor may also consider B12 deficiency to be rare, or a disease of advanced old age. It may therefore take an informed patient who is experiencing neurological symptoms to satisfy themselves that B12 deficiency is not involved in their illness.
You may have adequate B12 in your blood, but have a functional deficiency because of the way your body metabolises B12
Inborn errors of metabolism are caused by genes that result in less than perfect conversion of B12 at the cellular level. MTHFR gene mutations are common, and other similar genes have been identified. A person with such a disorder may have normal amounts of B12 in their blood, but be unable to use it properly. Given that B12 deficiency looks exactly like MS both clinically and on MRI, a serum B12 blood test that leads a doctor to rule out B12 deficiency would point to MS. However, if there was an inborn error of metabolism creating a practical or functional deficiency of B12, how would a neurologist determine that, unless they actually checked for it genetically or used a full B12 test panel that pointed to such a metabolic problem?
Is a search for inborn errors of metabolism that produce symptoms which look like MS standard practice when considering differential diagnosis for MS? Should it be?
People with a diagnosis of MS, or waiting for a diagnosis that is tending towards MS, could consider genetic counselling or consulting a metabolic specialist to determine whether they have genes which do not allow them to utilise vitamins properly, especially B group vitamins. Gene tests can be obtained online at relatively low cost, and can point to a metabolic error early in the disease process. Please see the Errors of B12 metabolism page for more information.
Just testing for serum B12 may not be enough. Other tests may be needed to get a full picture of your B12 status; You may be told that your tests are fine when you are not
As outlined above, there is a lack of consensus on what constitutes a normal range for serum B12, and serum B12 can even be replete, whilst a serious deficiency exists. However there are other tests that can give a much clearer picture of how B12 is being metabolised in the body.
Methylmalonic Acid (MMA): Elevated levels may indicate a B12 deficiency.
Homocysteine (Hcy): Elevated levels may also indicate a B12 deficiency. In Australia, the reference range for homocysteine appears to be 6.0 to 14.0 umol/L. This too would appear to be too high. According to Sally M. Pacholok and Jeffrey J. Stuart, writing in Could it be B12? the upper limit should be 12 umol/L. It would appear that having a homocysteine level more towards the middle of the range would be considered optimal. If your test is dismissed as ‘normal’, but your levels of homocysteine are above 10 or 12 umol/L you may want to discuss with your doctor whether you have a functional B12 deficiency, and investigate further.
Caution! The response of your doctor to a high or high normal homocysteine test may be to prescribe 'folate'. This could mask any ongoing B12 deficiency, and even worse could be detrimental to people who have a genetic incapacity to metabolise B12 properly, such as an MTHFR gene mutation, or another mutation which is related to the B12 methylation process. This article in the New England Journal of Medicine notes this masking effect in a discussion relating to B12 deficiency and the drug methotrexate.
Holotranscobalomin (HoloTC): Only around 20% of what is measured by the serum B12 test is an active form of B12 that can be used by our bodies. The HoloTC test measures this active B12, so gives a much more accurate picture of what is available to our bodies.
Given the severity of outcomes for people with confirmed or suspected MS, patients with early neurological symptoms should consider asking their doctors and/or neurologists for a full panel of B12 tests that include Serum B12, Holotranscobalomin, Homocysteine and Methylmalonic Acid, obtain a copy of the tests, and investigate the results until they are satisfied and comfortable that Vitamin B12 is not a factor in their illness. For people who have MS without an obvious B12 deficiency, consideration should be given to monitoring B12 status as the person ages.
There is a small time frame available to treat B12 deficiency successfully. After that, damage can be irreversible or only partially reversible
The critical window for treating B12 deficiency seems to be around six months and treatment after this time should still be addressed, but may be less effective at reversing the damage already done. When caught early, recovery from B12 deficiency can be dramatic. However, little is known about recovery in longstanding cases, but it may take months or years, and unfold in a stepwise rather than a linear fashion.
Since it may take months to get in to see a neurologist, and they may not test for B12 immediately, and a follow up consult may be some months later, it can be seen how urgent it may be for a primary care doctor to quickly and comprehensively check someone who is exhibiting neuropsychiatric signs and/or symptoms of B12 deficiency and for neurologists to consider this as a possibility early on.
If treated for B12 deficiency you may be given a type of B12 that is not the best for your body, or uses an inefficient delivery method, or both
If you have a deficiency, or are low on B12 and are trying to bring your levels up, your doctor may advise you to ‘take some B12’ or write a prescription. However, the form most easily found in health food stores and chemists is called cyanocobalomin and may not be the best form for you, or available in a form that reliably delivers the compound to where it is needed in your body.
Cyanocobalamin is a commercially produced synthetic chemical that is a non-active form of Vitamin B12 that has to be converted in the liver to a usable form. It contains cyanide. Before the body can use this form of B12, it has to be detoxified in the liver by de-cyaniding it to create the active form. The body may have to go through as many as four steps to convert cyanocobalamin to an active form of B12.
B12 is water soluble, is not stored in the body, and is non-toxic. However, if the patient has Leber’s hereditary optic neuropathy, the administration of cyanocobalamin could lead to blindness. Furthermore, without examination, it cannot be known how well a patient can convert this inactive B12 to active B12. If a patient has liver dysfunction, or other impaired detox capacity, they may not be able to detoxify the cyanide as well as others, and smokers are likely to have increased cyanide also.
The two different forms of active B12 are adenosylcobalamin and methylcobalamin and one or both of these may be more suitable for your circumstances than cyanocobalomin. These may not be easy to find at your local stockist of vitamins, but they are readily available online.
There are also several different delivery methods. Tablets and capsules have to make their way through the gastrointestinal tract and only relatively small amounts of B12 may be absorbed. It is difficult therefore to predict dosage rates, and to correct a deficiency, much larger doses in particular circumstances may be needed than what is recommended on packaging.
Injections of B12 are said to be an emergency measure for acute deficiency (to get levels up quickly), but because so much of the B12 is excreted so rapidly after an injection, they may not be of practical use in chronic deficiency. They are painful, and must usually be given to the patient in a clinic. Unless a different form is specifically asked for, they are likely to contain cyanocobalomin.
Sublingual tablets of active B12 are held under the tongue for long periods to allow the B12 to be absorbed more directly, but the long timeframes for which the tablets must be held in place may make this method quite impractical for some people.
Transdermal oils are rubbed into the skin to deliver B12 in tailored doses in a more readily absorbed manner, which is quickly completed as part of a daily routine. See b12oils.com
You may need to monitor your B12 status for life:
Vitamin B12 deficiency can be difficult to correct. Once corrected by supplementation, it does not mean that the underlying problem that was causing the deficiency has been corrected, or that monitoring or supplementation can be discontinued.
Links:
Comprehensive information on Vitamin B12 http://vitaminb12deficiency.net.au/Home.htm
Information on Vitamin B12 and transdermal oils b12oils.com
Vitamin B12 and MS http://vitaminb12deficiency.net.au/VB12MS.htm
You tube video relating to the book “Could it be B12?” by Pacholok and Stuart https://www.youtube.com/watch?v=QqjyAeOLyKM
The book “Could it be B12?” by Pacholok and Stuart http://b12awareness.org/about-us-sally-pacholok-jeffrey-stuart-could-it-be-b12-deficiency/
Biolab UK information on B12 deficiency and testing/reference ranges http://www.biolab.co.uk/docs/vitaminB12.pdf
Biolab UK information on Vitamin B12 uptake in the body, and testing issues
http://www.biolab.co.uk/index.php/cmsid__biolab_test/Vitamin_B12_and_methylmalonic_acid_profile
Australian Government Vitamin B12 review report, February 2014 http://www6.health.gov.au/internet/main/publishing.nsf/Content/7C28F0B6D06F9FFCCA257EB9001D769B/$File/Vitamin%20B12%20testing%20Review%20Report.pdf
Australian Government review of Vitamin B12 testing protocols http://www6.health.gov.au/internet/main/publishing.nsf/Content/7C28F0B6D06F9FFCCA257EB9001D769B/$File/Vitamin%20B12%20testing%20Protocol.pdf
MTHFR Australia discussion on whether B12 reference ranges are set too low http://www.mthfrsupport.com.au/vitamin-b12-reference-range-level-set-low/
Like progressive MS, B12 deficiency is also progressive, may take years to develop, and mimic all the symptoms of MS, including lesions found on MRI. Even where there is no obvious B12 deficiency or functional B12 deficiency, in MS patients where myelin repair is to be hoped for, the demand for B12 is likely to be increased as myelin is replaced in damaged areas of the CNS. Since progressive MS often develops later in life (usually after 40), could an actual or functional vitamin B12 deficiency be involved? A B12 deficiency could result in either an MS mis-diagnosis or be present along with confirmed MS, and optimising B12 metabolism could therefore be crucial in optimising health. Please see the ‘Errors of B group vitamin metabolism’ page for more information.
Vitamin B12 is essential for making DNA, forming and maintaining myelin sheaths, making neurotransmitters, and the production of red blood cells.
It is possible to be misdiagnosed with MS when you actually have B12 deficiency, and such a misdiagnosis can be devastating, but researchers have also found that many people with confirmed MS also have low B12. Optimising B12 in the diet, and checking that you are able to properly absorb and metabolise this vitamin can be part of your health optimisation strategy.
This article in the Journal of The Neurological Sciences discusses the difficulties of making a differential diagnosis between B12 deficiency and MS. http://www.direct-ms.org/pdf/NutritionMS/B12%20and%20MS.pdf
Did your doctor test you for B12 deficiency as soon as possible once neurological symptoms became evident, and are they monitoring your B12 status as you age?
In a nutshell:
- B12 deficiency can mimic the symptoms of MS, including lesions found in the CNS on MRI
- B12 deficiency can occur for many reasons, including poor diet, gastrointestinal difficulties in processing food, ageing, cellular metabolism problems, medications and surgery, amongst others
- Neurological damage may occur at levels much higher than the present lower limit set by some pathology labs
- Neurological damage may occur years before blood tests become unusual
- B12 deficiency is a complex subject and to fully understand all the biochemical interactions and the impact on the body is a field of study in itself
- Your doctor may think of B12 deficiency in terms of changes in your blood that relate to anaemia and not in terms of neuropsychiatric issues. Neuropsychiatric problems may precede blood abnormalities by many years
- If you are tested for B12 deficiency your doctor may not have in-depth knowledge of the issue and may be guided by pathology lab ranges that do not relate to your situation
- You may have adequate B12 in your blood, but have a functional deficiency because of the way your body metabolises B12
- Just testing for serum B12 may not be enough. Other tests may be needed to get a full picture of your B12 status
- You may be told that your tests are fine when you are not
- There is a small time frame available to treat B12 deficiency successfully. After that, existing damage can be irreversible
- If treated for B12 deficiency you may be given a type of B12 that is not the best for your body, or uses an inefficient delivery method, or both
- You may need to supplement, and monitor your B12 status for life
More detail:
Vitamin B12 deficiency can mimic the symptoms of MS, including lesions found on MRI
B12 deficiency can damage the myelin around the nerve and the nerve itself. Like progressive MS, damage can occur particularly in the spinal cord (Subacute combined degeneration of the spinal cord), and usually affects older adults after the age of 40. Like progressive MS, the neurological damage caused by B12 deficiency is not primarily inflammatory. Any invasion of dead patches of nerves by inflammatory immune cells in the CNS which has been damaged by B12 deficiency would presumably then only be associated with normal bodily ‘clean-up’ processes in the CNS.
Neurological symptoms could include decreased or brisk reflexes, loss of control of the toes and/or feet, loss of the sense of where parts of your body are positioned, foot drop and tripping over your toes, muscle weakness, ataxic gait (an unsteady, uncoordinated walk), weakness, burning, tingling and numbness, L’Hermittes sign (a sudden electric shock – like pain when the head is bent forward) sudden ice-pick pains, incontinence, brain atrophy (shrinkage), optic neuropathy, fatigue, insomnia, tremors and paralysis.
Psychiatric symptoms could include cognitive decline, ‘brain fog’ memory loss, confusion, disorientation, anxiety, depression, disorientation, paranoia, psychoses, schizophrenia, ADHD, and dementia.
B12 deficiency can occur for many reasons, including poor diet, gastro intestinal difficulties in processing food, ageing, metabolism problems, medications, and surgery amongst others
For a person to receive sufficient B12, it must firstly be present in the diet. B12 can only be found in animal products, you cannot obtain it from plants or sunlight. Also, being a water soluble vitamin (not stored in fat) your stocks must be replenished every day. So vegetarians and vegans are two groups who are at obvious risk of B12 deficiency. Additionally, some foods are B12 analogues and can block B12.
B12 is only needed in tiny amounts, but most people who are deficient in B12 eat foods with plenty of vitamins, because the second and third steps of absorption and metabolism are also crucial to getting B12 to where it is needed. Even if you are getting enough B12 in your food, you still have to absorb it and metabolise it properly.
Some of the problems with absorption can be not enough hydrochloric acid or the enzyme pepsin released in the stomach to break the B12 out of food. Dysfunction in the production of intrinsic factor or pancreatic proteases will also reduce the absorption of B12, as will gastrointestinal problems such as ulcerative colitis, Crohn’s disease, atrophic gastritis (inflammation and deterioration of the stomach lining), gastric ulcers, small intestinal bacterial overgrowth (SIBO), intestinal parasites or bacteria such as giardia, or H.pylori infections.
Use of medications such as proton pump inhibitors, antacids, and many others may lead to a deficiency in B12, including steroids and immune modulating drugs which are used to treat MS. A potent drug called Methotrexate which is sometimes used for Multiple Sclerosis, can also be related to B12 deficiency.
Vitamin C supplementation (Ascorbic acid) supplements can reduce the body’s capacity to absorb and utilise B12 and may convert it into biologically unavailable forms.
This article by San Pathology (a service operated by Sydney Adventist Hospital in Sydney Australia) concisely summarises some of the complexities surrounding B12 testing and deficiency, and notes the link between high dose Vitamin C and the destruction of B12 in the body.
http://www.sah.org.au/assets/files/PDFs/Pathology%20PDFs/Vitamin%20B12%20Update_San%20Dr.pdf
Surgery to remove part of the bowel or gastric bypass surgery can also lead to B12 deficiency, as can the use of proton pump inhibitors or antacids which reduce the hydrochloric acid levels, and antibiotics, which can reduce or eradicate populations of bacteria that are essential to the absorption of B12 in the gut. There are many other medicines which can create deficiencies, and the use of nitrous oxide for anaesthesia or recreational use can also cause an acute loss of B12 capacity in the body.
Hypothyroidism will accelerate B12 deficiency, as will low Vitamin B2. Genetic problems (See errors of B12 metabolism) or other metabolic problems may also cause people to be unable to process B12 effectively.
Ageing can be involved in many of these processes, and some authorities warn that anyone over forty is at increased risk of B12 deficiency, and anyone over sixty has up to a 40% risk of having a significant deficiency.
Once a deficiency is in place, it may be very difficult to correct using food alone, and many will require large doses of the correct type of supplements to overcome the deficiency and be monitored for life.
Nitrous oxide (an anaesthetic), inactivates B12 in the body and can cause life threatening harm. People with neurological diseases like MS should consider talking this over with their surgeon and/or anaesthetist, dentist or obstetrician before undergoing anaesthesia where this compound is going to be used, and consider having their B12 levels monitored before and afterwards.
Damage may occur at levels much higher than the lower limit set by pathology labs and Neurological damage may occur years before blood tests become unusual
Pathology lab reference ranges and units of measurement differ around the world and may even vary between pathology labs in the same country. However, reference ranges in your locality may have been set for changes in the blood, not neuropsychiatric change, and may be out of step with best practice in countries where this is recognised.
MTHFR Australia discusses this issue here http://www.mthfrsupport.com.au/vitamin-b12-reference-range-level-set-low/
In Australia, it is difficult to get comprehensive information on lab testing. It appears that total levels of B12 that are circulating in the blood are tested (serum B12) but this may include both active and inactive forms of the vitamin, leading to potentially inaccurately high reporting of levels.
Results are quoted in pmol/L, and one well known Australian lab’s reference range is 135-650 pmol/L. Doctors may therefore consider patients to be ‘normal’ even at the lower reference range, even if neuropsychiatric symptoms are present, and these could begin at levels of around 300 pmol/L (including brain shrinkage). At these lower ranges, there is a grey zone where damage may be occurring but it is ignored or ascribed to another cause that is non-treatable (like 'normal' ageing) or treatable with drugs (such as antidepressants) that do not address the cause. Japan is reported to have raised the lower limit to 500 pmol/L in the 1980’s.
However, steps are being made to improve this. Some lab reports now come with the following advice: “From 1 November 2014, active B12 (holotranscobalomin) testing will be performed on all patients with low or equivocal (up to 260 pmol/L) total B12 results. “ This acknowledges that B12 levels are risky up to 260 pmol/L and that testing for holotranscobalomin at the very least, will give a clearer picture.
A February 2014 Australian Government Department of Health MBS reviews - Vitamin B12 testing report noted that “There is currently no consensus on the best method to estimate vitamin B12 deficiency and vitamin B12 status. A 2011 systematic review … found low levels of test sensitivity and, to a lesser extent, specificity.” There is currently no internationally agreed definition for vitamin B12 deficiency based on clinical manifestations or on the ‘cut-off’ values that are used to define vitamin B12 deficiency, which vary between 120-200 pmol/L.”
Consider: this is a potentially devastating neuropsychiatric condition with a very narrow treatment window to avoid irreversible damage, and an Australian Government Health Department report has found that testing may be insensitive, and that there is no internationally agreed definition for laboratory or clinical B12 deficiency. It appears that doctors may be relying on essentially non-existent guidelines or at best potentially inaccurate or inconsistent guidelines for the diagnosis of this potentially crippling condition in Australia.
The report may be found here;
http://www6.health.gov.au/internet/main/publishing.nsf/Content/7C28F0B6D06F9FFCCA257EB9001D769B/$File/Vitamin%20B12%20testing%20Review%20Report.pdf
B12 deficiency is a complex subject and to fully understand all the biochemical interactions and the impact on the body is a field of study in itself; Your doctor may think of B12 deficiency in terms of changes in your blood that relate to anaemia and not in terms of neuropsychiatric issues. Neuropsychiatric problems may precede blood abnormalities by many years; If you are tested for B12 deficiency your doctor may not have in-depth knowledge of the issue and may instead be guided by pathology lab ranges
The above report notes the lack of an international standard for laboratory and clinical B12 deficiency. A review of the literature on the multiple intricacies involved in the subject will quickly convince the reader of the complexities involved in the clinical apprehension of B12 deficiency, interpreting lab results, diagnosing an outright deficiency or functional deficiency, unravelling causes, appreciating individual biochemical responses, and instituting and monitoring treatment. Entire books have been written on the subject. It is unlikely that general practitioners everywhere will be well acquainted with the topic or be fully aware of the pitfalls. Furthermore your doctor may have been trained to pick up on B12 deficiency in the presence of symptoms of anaemia, but neuropsychiatric symptoms can precede blood changes for many years, and the widespread use of folate fortified foods may mean that these changes are seen less and less, while an underlying B12 deficiency remains.
Jill Benson, writing in the publication Vitamin B12 deficiency - why refugee patients are at high risk notes: “The medical profession has often relied on the presence of megaloblastic anaemia as an indication to check vitamin B12 status. Changes in the blood film with macrocytosis and hypersegmented neutrophils are late manifestations of folate or vitamin B12 deficiency and should not be relied upon as an indication for testing of vitamin B12 levels. In addition, those with a very low vitamin B12 and a normal folate may not have a megaloblastic picture but will still be at risk of developing neuropsychiatric and cardiovascular sequelae. Serum concentrations of vitamin B12 may be low in the presence of normal tissue levels if there is concomitant folate deficiency, pregnancy, iron deficiency or in certain rare inherited disorders of vitamin B12 metabolism. There is no universal agreement on the recommendations for the treatment of vitamin B12 deficiency in those who do not have pernicious anaemia. All patients with vitamin B12 < 220pmol/L should have their H. pylori status ascertained with serum antibodies (if they have not had previous treatment), breath test or stool antigen...”
Your doctor may also consider B12 deficiency to be rare, or a disease of advanced old age. It may therefore take an informed patient who is experiencing neurological symptoms to satisfy themselves that B12 deficiency is not involved in their illness.
You may have adequate B12 in your blood, but have a functional deficiency because of the way your body metabolises B12
Inborn errors of metabolism are caused by genes that result in less than perfect conversion of B12 at the cellular level. MTHFR gene mutations are common, and other similar genes have been identified. A person with such a disorder may have normal amounts of B12 in their blood, but be unable to use it properly. Given that B12 deficiency looks exactly like MS both clinically and on MRI, a serum B12 blood test that leads a doctor to rule out B12 deficiency would point to MS. However, if there was an inborn error of metabolism creating a practical or functional deficiency of B12, how would a neurologist determine that, unless they actually checked for it genetically or used a full B12 test panel that pointed to such a metabolic problem?
Is a search for inborn errors of metabolism that produce symptoms which look like MS standard practice when considering differential diagnosis for MS? Should it be?
People with a diagnosis of MS, or waiting for a diagnosis that is tending towards MS, could consider genetic counselling or consulting a metabolic specialist to determine whether they have genes which do not allow them to utilise vitamins properly, especially B group vitamins. Gene tests can be obtained online at relatively low cost, and can point to a metabolic error early in the disease process. Please see the Errors of B12 metabolism page for more information.
Just testing for serum B12 may not be enough. Other tests may be needed to get a full picture of your B12 status; You may be told that your tests are fine when you are not
As outlined above, there is a lack of consensus on what constitutes a normal range for serum B12, and serum B12 can even be replete, whilst a serious deficiency exists. However there are other tests that can give a much clearer picture of how B12 is being metabolised in the body.
Methylmalonic Acid (MMA): Elevated levels may indicate a B12 deficiency.
Homocysteine (Hcy): Elevated levels may also indicate a B12 deficiency. In Australia, the reference range for homocysteine appears to be 6.0 to 14.0 umol/L. This too would appear to be too high. According to Sally M. Pacholok and Jeffrey J. Stuart, writing in Could it be B12? the upper limit should be 12 umol/L. It would appear that having a homocysteine level more towards the middle of the range would be considered optimal. If your test is dismissed as ‘normal’, but your levels of homocysteine are above 10 or 12 umol/L you may want to discuss with your doctor whether you have a functional B12 deficiency, and investigate further.
Caution! The response of your doctor to a high or high normal homocysteine test may be to prescribe 'folate'. This could mask any ongoing B12 deficiency, and even worse could be detrimental to people who have a genetic incapacity to metabolise B12 properly, such as an MTHFR gene mutation, or another mutation which is related to the B12 methylation process. This article in the New England Journal of Medicine notes this masking effect in a discussion relating to B12 deficiency and the drug methotrexate.
Holotranscobalomin (HoloTC): Only around 20% of what is measured by the serum B12 test is an active form of B12 that can be used by our bodies. The HoloTC test measures this active B12, so gives a much more accurate picture of what is available to our bodies.
Given the severity of outcomes for people with confirmed or suspected MS, patients with early neurological symptoms should consider asking their doctors and/or neurologists for a full panel of B12 tests that include Serum B12, Holotranscobalomin, Homocysteine and Methylmalonic Acid, obtain a copy of the tests, and investigate the results until they are satisfied and comfortable that Vitamin B12 is not a factor in their illness. For people who have MS without an obvious B12 deficiency, consideration should be given to monitoring B12 status as the person ages.
There is a small time frame available to treat B12 deficiency successfully. After that, damage can be irreversible or only partially reversible
The critical window for treating B12 deficiency seems to be around six months and treatment after this time should still be addressed, but may be less effective at reversing the damage already done. When caught early, recovery from B12 deficiency can be dramatic. However, little is known about recovery in longstanding cases, but it may take months or years, and unfold in a stepwise rather than a linear fashion.
Since it may take months to get in to see a neurologist, and they may not test for B12 immediately, and a follow up consult may be some months later, it can be seen how urgent it may be for a primary care doctor to quickly and comprehensively check someone who is exhibiting neuropsychiatric signs and/or symptoms of B12 deficiency and for neurologists to consider this as a possibility early on.
If treated for B12 deficiency you may be given a type of B12 that is not the best for your body, or uses an inefficient delivery method, or both
If you have a deficiency, or are low on B12 and are trying to bring your levels up, your doctor may advise you to ‘take some B12’ or write a prescription. However, the form most easily found in health food stores and chemists is called cyanocobalomin and may not be the best form for you, or available in a form that reliably delivers the compound to where it is needed in your body.
Cyanocobalamin is a commercially produced synthetic chemical that is a non-active form of Vitamin B12 that has to be converted in the liver to a usable form. It contains cyanide. Before the body can use this form of B12, it has to be detoxified in the liver by de-cyaniding it to create the active form. The body may have to go through as many as four steps to convert cyanocobalamin to an active form of B12.
B12 is water soluble, is not stored in the body, and is non-toxic. However, if the patient has Leber’s hereditary optic neuropathy, the administration of cyanocobalamin could lead to blindness. Furthermore, without examination, it cannot be known how well a patient can convert this inactive B12 to active B12. If a patient has liver dysfunction, or other impaired detox capacity, they may not be able to detoxify the cyanide as well as others, and smokers are likely to have increased cyanide also.
The two different forms of active B12 are adenosylcobalamin and methylcobalamin and one or both of these may be more suitable for your circumstances than cyanocobalomin. These may not be easy to find at your local stockist of vitamins, but they are readily available online.
There are also several different delivery methods. Tablets and capsules have to make their way through the gastrointestinal tract and only relatively small amounts of B12 may be absorbed. It is difficult therefore to predict dosage rates, and to correct a deficiency, much larger doses in particular circumstances may be needed than what is recommended on packaging.
Injections of B12 are said to be an emergency measure for acute deficiency (to get levels up quickly), but because so much of the B12 is excreted so rapidly after an injection, they may not be of practical use in chronic deficiency. They are painful, and must usually be given to the patient in a clinic. Unless a different form is specifically asked for, they are likely to contain cyanocobalomin.
Sublingual tablets of active B12 are held under the tongue for long periods to allow the B12 to be absorbed more directly, but the long timeframes for which the tablets must be held in place may make this method quite impractical for some people.
Transdermal oils are rubbed into the skin to deliver B12 in tailored doses in a more readily absorbed manner, which is quickly completed as part of a daily routine. See b12oils.com
You may need to monitor your B12 status for life:
Vitamin B12 deficiency can be difficult to correct. Once corrected by supplementation, it does not mean that the underlying problem that was causing the deficiency has been corrected, or that monitoring or supplementation can be discontinued.
Links:
Comprehensive information on Vitamin B12 http://vitaminb12deficiency.net.au/Home.htm
Information on Vitamin B12 and transdermal oils b12oils.com
Vitamin B12 and MS http://vitaminb12deficiency.net.au/VB12MS.htm
You tube video relating to the book “Could it be B12?” by Pacholok and Stuart https://www.youtube.com/watch?v=QqjyAeOLyKM
The book “Could it be B12?” by Pacholok and Stuart http://b12awareness.org/about-us-sally-pacholok-jeffrey-stuart-could-it-be-b12-deficiency/
Biolab UK information on B12 deficiency and testing/reference ranges http://www.biolab.co.uk/docs/vitaminB12.pdf
Biolab UK information on Vitamin B12 uptake in the body, and testing issues
http://www.biolab.co.uk/index.php/cmsid__biolab_test/Vitamin_B12_and_methylmalonic_acid_profile
Australian Government Vitamin B12 review report, February 2014 http://www6.health.gov.au/internet/main/publishing.nsf/Content/7C28F0B6D06F9FFCCA257EB9001D769B/$File/Vitamin%20B12%20testing%20Review%20Report.pdf
Australian Government review of Vitamin B12 testing protocols http://www6.health.gov.au/internet/main/publishing.nsf/Content/7C28F0B6D06F9FFCCA257EB9001D769B/$File/Vitamin%20B12%20testing%20Protocol.pdf
MTHFR Australia discussion on whether B12 reference ranges are set too low http://www.mthfrsupport.com.au/vitamin-b12-reference-range-level-set-low/
Like progressive MS, B12 deficiency is also progressive, may take years to develop, and mimic all the symptoms of MS, including lesions found on MRI. Even where there is no obvious B12 deficiency or functional B12 deficiency, in MS patients where myelin repair is to be hoped for, the demand for B12 is likely to be increased as myelin is replaced in damaged areas of the CNS. Since progressive MS often develops later in life (usually after 40), could an actual or functional vitamin B12 deficiency be involved? A B12 deficiency could result in either an MS mis-diagnosis or be present along with confirmed MS, and optimising B12 metabolism could therefore be crucial in optimising health. Please see the ‘Errors of B group vitamin metabolism’ page for more information.