Title

Subtitle

B12 in Brief

  • 82% of all EPI dogs have insufficient B12 levels that if not corrected will prohibit the dog from optimally healing. Lack of weight gain, lethargy, lack of appetite, continued loose stools, etc., all suggest possible insufficient B12.
  • If possible, ask for a Cobalamin (B12) blood test to be done at the same time as a TLI test to save money. Dog must be fasted for 12-15 hours. Texas A&M Gastro Lab http://vetmed.tamu.edu/gilab/service/assays/b12folate is the premier laboratory to test B12 levels.
  • The current preferred B12 regimen is with generic B12 injections not multivitamin or complex B12 injections. Read below for proper dosing and various dosing regimens.
  • B12 levels in an EPI patient needs to be in the normal upper-mid range level... just normal range is not sufficient!
  • In general, over-the-counter B12 pills tend not to work. However, B12 pills that have the intrinsic factor included tends to work very well at increasing the B12 levels in most EPI dogs.  Although the Intrinsic Factor is needed to transport "digested" B12 into the blood stream, supposedly the intrinsic factor delivery system should not be destroyed by EPI- -however- - oddly enough in most cases when B12 pill with the intrinsic factor is given it has the best success rate for increasing B12 levels along with the recommended protocol of giving B12 shots. ***Sometimes some B12 pills given at very high doses without the intrinsic factor included may or may not work... and again, oddly enough, clinically this should work, but in reality it doesn't always work ***                  (May 2016- -this is currently being studied at TAMU with possibly promising results)  
  • The few products that now produce B12 pills with the intrinsic factor included that "appear" to work very well, although no clinical studies have been done to substantiate this. We do always recommend doing injections first (per current protocol.. although this may soon change) , if you chose to, maintain the upper B12 levels with pills, talk to your vet about using Wonderlabs Trinfac B12 (Methycobalamin B12 with the intrinsic factor) or...  Wonderlabs PET Factor B-12 (also with Methycobalamin B12 with the intrinsic factor)  capsules http://www.wonderlabs.com/itemleft.php?itemnum=K9688 or if you are in the UK, you can purchase B12 with Intrinsic Factor from Chemeyes, http://www.chemeyes.co.uk/ (similar to "Trinfac/Pet Factor B-12") . 
  • Sometimes in "some" cases sublingual tabs help- -but check ingredients for dangerous artificial sweeteners. Avoid Xylitol, and ask your vet if it is safe if it contains Mannitol or Sorbital. Also with sublinqual tabs, there have been multiple reports of these pills working for a while and then no longer effective.
  • If upon initial EPI diagnosis, your dog has insufficient B12 levels... talk to your vet about also possibly treating for SIBO as SID/SIBO can deplete B12 stores.



Epi4Dogs is pleased to announce that Wonderlabs is offering a deep international shipping discount - no expiration date - on ALL their products. Many of our EPI members have used Wonderlabs B12 + Instrinsic Factor capsules or PetFactor B12 as their B12 supplementation with approximately 95-98% success rate with increasing the B12 levels in our compromised EPI dogs. Please feel free to check out either the Pet Factor B12 product https://www.wonderlabs.com/itemleft.php?itemnum=K9688 or the Trinfac B12 product https://www.wonderlabs.com/itemleft.php?itemnum=6881.... or any other Wonderlabs product.


May 2016  - Oral B12 supplementation research

As of May 2016....  B12 shots are still the proper protocol for B12 for EPI dogs. Currently there are oral B12 studies currently being conducted at TAMU with some promise http://vetmed.tamu.edu/gilab/research/oral-cobalamin-study

However, until we have further confirmation, at this time, Epi4Dogs position on B12 is the following: 

  • B12 injections work most of the time with simple cyanocobalamin serum, if not, change the version of the B12 serum to Hydroxycobalmin or Methycobalamin serum
  • Oral B12 Methycobalmin with Intrinsic factor works 98% of the time
  • Oral B12 Methycobalamin without Intrinsic Factor may or may not work, worth trying, but observe dog closely for 3 months in case it doesn?t work.
  • Oral B12 Cyanocobalmin without Intrinsic Factor may or may not work, worth trying, but observe dog closely for 3 months in case http://onlinelibrary.wiley.com/doi/10.1111/jvim.13797/fullit doesn?t work. 
 
Jan 2016
 "Oral Cobalamin Supplementation in Dogs with Chronic Enteropathies and Hypocobalaminemia" 
  1. L. Toresson1,2,*
  2. J.M. Steiner3
  3. J.S. Suchodolski3 and
  4. T. Spillmann1

 
.... the dosing for the oral Cyanocobalmin is slated to be the same as the shots... by weight:

cats, dogs up to 5 kg (10 lb)                       

250 µg   this is also 250mcg of oral B12

dogs, 5-15kg (10-30 lb)

400 µg this is also 400 mcg of oral B12

dogs, 15-30 kg (30-65 lb)

800 µg this is also 800 mcg of oral B12

dogs, 30-45 kg (65-100 lb)

1200 µg this is also 1200 mcg of oral B12

dogs above 45 kg (100 lb)

1500 µg this is also 1500 mcg of oral B12

Below are links to PDF's of other 2015+2016 specific company research supporting an oral B12 product TAMU is currently reviewing.... however... do to multiple and repeated individual cases of EPI owners tried and tested B12 levels with and without the intrinsic factor included in oral B12.... Epi4Dogs current position is to recommend oral B12 with intrinsic factor over products without the intrinsic factor included (even though this too may work in cases)  until additional research can prove otherwise........ 

 1 CN_2016_Nutramax_D Cobalamin Deficiency FNL.pdf 

2 Cobalamin Deficiency Info Sheet 04.1151.00.pdf

 

 

*** Please follow the current TAMU (Texas A&M University) B12 protocol for EPI dogs and cats  ***

The difference B12 can make ......

The below is an actual chart of Seth's EPI dog, "Donna"   .... that visually shows the amazing difference B12 can make in an EPI dog that did not have optimal B12 levels.  Thank you Seth for sharing this with us!

 3/26/2013 - 2nd B12 shot - 53 lbs

4/2/2013 - 3rd B12 shot - 56.8 lbs

4/10/2013 - 4th B12 shot - 58.9 lbs

4/17/2013 - 5th B12 shot - 60 lbs

4/22/2013 - 2 cups a meal, 2 times a day. (my vet recommended we only feed her twice a day since she gained back almost 20 lbs :))

5/15/2013 - 6th B12 shot 63.8 lbs

6/27/2013 - 7th B12 shot - 64.5 lbs 

9/1/2013 - Her stool was not looking good so based on the advice of everybody here, I started her on the Tylan again. I will include it in her meal for 45 days.

9/4/2013 - 64 lbs

11/7/2013 - 60 lbs. Her stool went back to normal. I think the Tylan for 45 days was successful. :)


  

revised TAMU cobalamin (B12) therapy - revised January 2011.... re-confirmed 9/20/12

 (per 2010  Dr. Jorg Steiner (TAMU) in his presentation "Endoscopy is not  enough: how lab work can help in the diagnosis of gastrointestinal problems" 82% of all EPI dogs have deficient B12 levels)

January 2011 - from TEXAS A & M UNIVERSITY website

Current Website Link: http://vetmed.tamu.edu/gilab/research/cobalamin-information 

Previous Website Link: http://vetmed.tamu.edu/gilab/research/cobalamin-information#dosing

Cobalamin: Diagnostic use and therapeutic considerations

Dog

Introduction

Cobalamin (Vitamin B12) is a water-soluble, cobalt-containing vitamin with an important role in biochemical processes referred to as single carbon transfers. During these reactions, functional units such as methyl groups (-CH3) are transferred onto or between biologically important compounds. Cobalamin is a co-factor for at least three enzymes that carry out these types of reactions, acting as a transitional carrier of the single carbon group. A typical reaction catalyzed by a cobalamin dependant enzyme, methionine synthase, is illustrated in figure 1. Single carbon biochemistry is an area of great interest in the human population, as deficiencies in the activity of these enzymes may be associated with hyperhomocysteinemia. Hyperhomocysteinemia is a recognized risk factor for cardiovascular disease. Deficiency in cobalamin may also be associated with demyelinating neuropathies, dementia and megaloblastic anemia (Pernicious Anemia) in human patients.

In companion animal medicine, most attention to cobalamin has been directed towards its use as a diagnostic marker for gastrointestinal disease. Recent evidence from studies at the Gastrointestinal Laboratory have also shown that supplementation of cobalamin is important to get the best response to therapy for gastrointestinal disease.

A typical cobalamin dependant reaction, where a methyl group (-CH3) is added to homocysteine to make methionine

Figure 1: A typical cobalamin dependant reaction, where a methyl group (-CH3) is added to homocysteine to make methionine

Cobalamin Deficiency in Gastrointestinal Disease

In animals with reduced cobalamin absorption, regardless of the cause, it is reasonable to expect that eventual depletion of bodily cobalamin stores will occur and cobalamin deficiency will ensue. As all cells in the body require cobalamin for single carbon metabolism, it has been hypothesized that cobalamin deficiency may actually contribute to the clinical signs and manifestations of gastrointestinal disease in some patients. Studies of radiolabelled cobalamin in cats have demonstrated that the half-life of this compound is significantly reduced with gastrointestinal disease.

While the serum concentration of cobalamin is used diagnostically, the reactions catalyzed by cobalamin dependant enzymes occur in the mitochondria, making it difficult to assess the state of cobalamin availability in the patient. Tissue-level deficiency of cobalamin is associated with an increase in the urinary and serum concentrations of an organic acid called methylmalonic acid, which is an alternative product of a cobalamin dependant pathway within the mitochondria. Using this compound as a marker of cobalamin deficiency, we have been able to demonstrate that cats and dogs with very low serum cobalamin do indeed have a significant tissue-level cobalamin deficiency (Figure 2.). Interestingly, in cats, there was no change in serum concentration of homocysteine (see figure 1. Elevation in homocysteine is expected with cobalamin deficiency due to reduced methionine synthase activity) even in the face of extreme cobalamin deficiency. In dogs, preliminary evidence suggests that there is an increase in serum homocysteine concentration with reduced serum cobalamin concentration.

Serum concentrations of methylmalonic acid are extremely high in cats with cobalamin deficiency, when compared to clinically healthy cats with normal serum cobalamin

Figure 2: Serum concentrations of methylmalonic acid are extremely high in cats with cobalamin deficiency, when compared to clinically healthy cats with normal serum cobalamin.

Cobalamin Therapy

As described above, there is compelling evidence that significant tissue-level cobalamin deficiency is present in some companion animal patients with gastrointestinal disease. The significance of this finding for the clinical management of these patients is also becoming clearer. A recent study has examined the effect of cobalamin supplementation on the outcomes of treatment for feline patients with severe cobalamin deficiency and histories suggesting chronic gastrointestinal disease.5 In this study, serum concentrations of methylmalonic acid normalized following parenteral cobalamin supplementation, indicating that cobalamin deficiency was the cause of the high methylmalonic acid in serum. There was an overall weight gain in these patients, and a decrease in the frequency of clinical signs such as vomiting and diarrhea. During the course of the study, there was no change to the therapeutic regime other than the introduction of parenteral cobalamin supplementation.

Dogs with exocrine pancreatic insufficiency will commonly present with subnormal serum cobalamin concentrations. Therapy with bovine pancreatic enzyme extracts is not sufficient to restore cobalamin absorption in dogs with EPI, as intrinsic factor appears to be species specific. Failure to absorb cobalamin in dogs with EPI may be due to all three potential causes of low serum cobalamin. Pancreatic secretion of intrinsic factor is reduced or absent, secondary bacterial overgrowth of the intestine is common, and the mucosa may be compromised by the presence of excessive bacterial numbers and toxic metabolites. Dogs with exocrine pancreatic insufficiency should be considered at high risk for the development of cobalamin deficiency. As clinical signs of cobalamin deficiency include chronic wasting or failure to thrive, malaise, and gastrointestinal signs such as diarrhea, serum cobalamin concentration should be measured in any dog with poor response to enzyme replacement therapy for EPI.

Therapeutic Dosing and Route

Cobalamin should be supplemented whenever serum cobalamin concentration is in the low normal range (approximately less than 300 ng/L) in both dogs and cats. Most commonly, cyanocobalamin is chosen for supplementation, as it is both widely available and inexpensive. Very little evidence-based information about cobalamin supplementation in dogs and cats is available. However, as in people, cobalamin deficiency leads to cobalamin malabsorption so that cobalamin should always be supplemented parenterally. Since cobalamin is a water-soluble vitamin, excess cobalamin is excreted through the kidneys and clinical disease due to over-supplementation has not been described.

We currently recommend SC injection of 250 µg per injection in cats and, depending on the size of the patient, 250-1500 µg per injection in dogs. We have recently changed our suggested dosing schedule for cobalamin supplementation: q 7 days for 6 weeks, then one dose after 30 days, and retesting 30 days after the last dose. If the underlying disease process has resolved and cobalamin body stores have been replenished, serum cobalamin concentration should be supranormal at the time of reevaluation. However, if serum cobalamin concentration is within the normal range, treatment should be continued at least monthly and the owner should be forewarned that clinical signs may recur sometime in the future. Finally, if the serum cobalamin concentration at the time of reevaluation is subnormal, further work-up is required to definitively diagnose the underlying disease process and cobalamin supplementation should be continued weekly or bi-weekly.

It should be pointed out that in rare cases cobalamin supplementation fails to increase serum cobalamin concentration for reasons that are not currently understood. In these cases another formulation of cobalamin, such as hydroxocobalamin, might be effective.
Cobalamin may also have a pharmacologic effect as an appetite stimulant. Anorectic feline patients with cobalamin deficiency often start to eat again once they are being supplemented and appetite wanes once again when cobalamin is no longer administered weekly, despite a normal serum cobalamin concentration. In these patients cobalamin supplementation should be continued on a weekly or biweekly dosing schedule.

Recommendations

We currently recommend that all dogs and cats with chronic histories of gastrointestinal disease should have serum cobalamin concentrations measured. This is particularly important in any case with sub-optimal response to previously instituted therapy. As cobalamin is inexpensive, water soluble and any excess is readily disposed, cobalamin supplementation should certainly be considered for any animal with a serum cobalamin concentration lower than the laboratory reference range.

Further Reading

  1. Simpson KW, Fyfe J, Cornetta A, Sachs A, Strauss-Ayali D, Lamb SV, Reimers TJ (2001), Subnormal concentrations of serum cobalamin (Vitamin B12) in cats with gastrointestinal disease, Journal of Veterinary Internal Medicine 15: 26-32
  2. Vaden SL, Wood PA, Ledley FD, Cornwell PE, Miller RT, Page R (1992), Cobalamin deficiency associated with methylmalonic acidemia in a cat, Journal of the American Veterinary Medical Association 200 No.8: 1101-1103
  3. Ruaux CG, Steiner JM, Williams DA. (2001), Metabolism of amino acids in cats with severe cobalamin deficiency. American Journal of Veterinary Research 62: 1852-1858
  4. Ruaux CG, Steiner JM, Williams DA. (2005), Early Biochemical and Clinical Responses to Cobalamin Supplementation in Cats with Signs of Gastrointestinal Disease and Severe Hypocobalaminemia. Journal of Veterinary Internal Medicine 19: 155-160
  5. Simpson KW, Morton DB, Batt RM (1989), Effect of exocrine pancreatic insufficiency on cobalamin absorption in dogs, American Journal of Veterinary Research 50: 1233-1236

Gastrointestinal Laboratory | Dr. Jörg M. Steiner | Department of Small Animal Clinical Sciences
Texas A&M University | 4474 TAMU | College Station, TX 77843-4474
Phone 979 862 2861 | Fax 979 862 2864 | [email protected] | Web Content: Dr. Jan Suchodolski

B12 Veterinarian Protocol SUMMATION FOR EPI DOG OWNERS:

Once done with the weekly injections of B12 for 6 weeks....the next shot should be given at 30 days and then re-test after 30 days. The following are just suggestions on what B12 protocol to "start" following after you receive the B12 test results.  As time passes, the B12 regimen may need to be adjusted.

  • if the B12 re-tested levels come back at normal B12 levels... this means the EPI dog most likely NEEDS B12 injections to be given monthly.... and most likely for life.... and low or low normal B12 may occur yet again.
  • if the B12 re-tested levels come back at very high normal B12 levels... this means no shot needed right now but re-test in the future (maybe in 3 to 6 months) to ascertain what the B12 levels are at and how frequently you may need to supplement with SQ B12 to maintain appropriate high normal B12 levels
  • if the B12 re-tested levels come back at low-normal or low B12 levels... this means that the dog needs to be placed on weekly or bi-weekly B12 injections.
  • if the B12 re-tested levels come back at still low or low nornal B12 levels even after weekly or bi-weekly injections... this means that your EPI dog may require a different compound of B12, such as hydroxocobalamin vs. cobalamin.
It is very important that people with EPI dogs realize that when these dogs develop an issue with B12... it will most likely be a lifelong issue .... and that again, as we find with other facets of EPI,  you simply have to find the right balance of B12 to maintain.

B12 tutorial by Oregon State University

Oregon State University has an EXCELLENT tutorial on the process of B12 in the body put together by:

The Micronutrient Information Center is a public service of the Linus Pauling Institute. .

 Please click on this link to read this informational piece in it's entirety:

http://lpi.oregonstate.edu/mic/vitamins/vitamin-B12 

This link leads to a website provided by the Linus Pauling Institute at Oregon State University.  Epi4Dogs is not affiliated or endorsed by the Linus Pauling Institute or Oregon State University. 

previous TAMU'S  Cobalamin - B12Protocol

Texas A & M ....PREVIOUS ....B12 protocol...... recently updated January 2011 (see above)

Taken from Texas A&M G.I. Lab previous protocol for B12

Cobalamin (Vitamin B12) is a water-soluble, cobalt-containing vitamin with an important role in biochemical processes referred to as single carbon transfers. During these reactions, functional units such as methyl groups (-CH3) are transferred onto or between biologically important compounds. Cobalamin is a co-factor for at least three enzymes that carry out these types of reactions, acting as a transitional carrier of the single carbon group. A typical reaction catalyzed by a cobalamin dependant enzyme, methionine synthase, is illustrated in figure 1. Single carbon biochemistry is an area of great interest in the human population, as deficiencies in the activity of these enzymes may be associated with hyperhomocysteinemia. Hyperhomocysteinemia is a recognized risk factor for cardiovascular disease. Deficiency in cobalamin may also be associated with demyelinating neuropathies, dementia and megaloblastic
anemia (Pernicious Anemia) in human patients.

In companion animal medicine, most attention to cobalamin has been directed towards its use as a diagnostic marker for gastrointestinal disease. Recent evidence from studies at the Gastrointestinal Laboratory have also shown that supplementation of cobalamin is important to get the best response to therapy for gastrointestinal disease.

COBALAMIN DEFICIENCY IN GASTROINTESTINAL DISEASE

In animals with reduced cobalamin absorption, regardless of the cause, it is reasonable to expect that eventual depletion of bodily cobalamin stores will occur and cobalamin deficiency will ensue. As all cells in the body require cobalamin for single carbon metabolism, it has been hypothesized that cobalamin deficiency may actually contribute to the clinical signs and manifestations of gastrointestinal disease in some patients. Studies of radiolabelled cobalamin in cats have demonstrated that the half-life of this compound is significantly reduced with gastrointestinal disease.

While the serum concentration of cobalamin is used diagnostically, the reactions catalyzed by cobalamin dependant enzymes occur in the mitochondria, making it difficult to assess the state of cobalamin availability in the patient. Tissue-level deficiency of cobalamin is associated with an increase in the urinary and serum concentrations of an organic acid called methylmalonic acid, which is an alternative product of a cobalamin dependant pathway within the mitochondria. Using this compound as a marker of cobalamin deficiency, we have been able to demonstrate that cats and dogs with very low serum cobalamin do indeed have a significant tissue-level cobalamin deficiency (Figure 2.). Interestingly, in cats, there was no change in serum concentration of homocysteine (see figure 1. Elevation in homocysteine is expected with cobalamin deficiency due to reduced methionine synthase activity) even in the face of extreme cobalamin deficiency. In dogs, preliminary evidence suggests that there is an increase in serum homocysteine concentration with reduced serum cobalamin concentration.

 

COBALAMIN THERAPY

As described above, there is compelling evidence that significant tissue-level cobalamin deficiency is present in some companion animal patients with gastrointestinal disease. The significance of this finding for the clinical management of these patients is also becoming clearer. A recent study has examined the effect of cobalamin supplementation on the outcomes of treatment for feline patients with severe cobalamin deficiency and histories suggesting chronic gastrointestinal disease.5 In this study, serum concentrations of methylmalonic acid normalized following parenteral cobalamin supplementation, indicating that cobalamin deficiency was the cause of the high methylmalonic acid in serum. There was an overall weight gain in these patients, and a decrease in the frequency of clinical signs such as vomiting and diarrhea. During the course of the study, there was no change to the therapeutic regime other than the introduction of parenteral cobalamin supplementation.

Dogs with exocrine pancreatic insufficiency will commonly present with subnormal serum cobalamin concentrations.
Therapy with bovine pancreatic enzyme extracts is not sufficient to restore cobalamin absorption in dogs with EPI, as intrinsic factor appears to be species specific. Failure to absorb cobalamin in dogs with EPI may be due to all three potential causes of low serum cobalamin. Pancreatic secretion of intrinsic factor is reduced or absent, secondary bacterial overgrowth of the intestine is common, and the mucosa may be compromised by the presence of excessive bacterial numbers and toxic metabolites. Dogs with exocrine pancreatic insufficiency should be considered at high risk for the development of cobalamin deficiency. As clinical signs of cobalamin deficiency include chronic wasting or failure to thrive, malaise, and gastrointestinal signs such as diarrhea, serum cobalamin concentration should be measured in any dog with poor response to enzyme replacement therapy for EPI.

THERAPEUTIC DOSING AND ROUTE

As cobalamin deficiency in companion animals is usually secondary to reduced cobalamin absorptive capacity, the use of dietary cobalamin supplementation is at best highly inefficient, and most likely ineffective, in the restoration of bodily cobalamin stores. The route of choice for cobalamin supplementation is by parenteral injection. Generic formulations of cobalamin are readily available and extremely cost effective. The doses we currently recommend for dogs and cats are given in table 1. The dose regime is typically one dose weekly for six weeks, one dose every two weeks for six weeks, then dose monthly. Remeasure serum cobalamin concentrations one month after last administration. Unless the intestinal disease is totally resolved, it is likely that the patient will continue to require regular cobalamin supplementation, the frequency necessary is assessed by regular measurement of serum cobalamin concentration.

Table 1 : Recommended dosages of cobalamin for dogs and cats

 

Animal Bodyweight Range
Dose/injection
cats, dogs up to 5 kg (10 lb)
250 µg
dogs, 5-15kg (10-30 lb)
400 µg
dogs, 15-30 kg (30-65 lb)
800 µg
dogs, 30-45 kg (65-100 lb)
1200 µg
dogs above 45 kg (100 lb)
1500 µg

Most generic cobalamin preparations are 1mg/ml, i.e. 1000µg/ml. Multi-vitamin and B-complex injectable formulations contain very much lower concentrations of cobalamin, and often cause pain at the injection site, their use is not recommended.

Cobalamin is non-irritant and may be given subcutaneously or intramuscularly, most clinicians deliver it subcutaneously.

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The Importance of B12 in EPI Dogs - Updated: March 5, 2010

Journal of Veterinary Internal Medicine

Volume 21 Issue 1, Pages 54 - 60 Published Online: 5 Feb 2008 -

The results of a study " Prognostic Factors in Canine Exocrine Pancreatic Insufficiency: Prolonged Survival is Likely if Clinical Remission is Achieved" performed at the University of Liverpool School of Veterinary Science by Daniel J. Batchelor, Peter-John M. Noble, Rebecca H. Taylor, Peter J. Cripps, Alexander J. German, published in the Journal of Veterinary Internal Medicine in February 2008 concludes that "Long-term prognosis in canine EPI is favorable for dogs that survive the initial treatment period. Although there are few predictors of good RIT (Response to Initial Treatment) or long-term survival, severe cobalamin deficiency is associated with shorter survival. Therefore, parenteral cobalamin supplementation should be considered when hypocobalaminemia is documented." 

The ABSTRACT of the study is as follows:

Background: Response to therapy in canine exocrine pancreatic insufficiency (EPI) varies considerably, making it difficult to determine prognosis for individual patients.
Hypothesis: Response to initial treatment (RIT) and survival are affected by signalment, clinical variables, and therapeutic regimen employed.
Animals: Client-owned dogs diagnosed with EPI between 1990 and 2002 were included in this study.
Methods: The study comprised a retrospective, questionnaire-based review.

Results: One hundred seventy-eight completed questionnaires were returned. RIT was good in 60% of treated dogs, partial in 17%, and poor in 23%. On univariate analysis, dogs that received antibiotics (P = .037) or had high serum folate concentration (P = .037) had a poorer RIT. On multivariate analysis, there were no strong predictors of good RIT. Nineteen percent of treated dogs were euthanized within 1 year, but overall median survival time for treated dogs was 1919 days. No clear benefit of changing to a fat-restricted diet could be demonstrated, but marked hypocobalaminemia (< 100 ng/L) was associated with shorter survival (P = .012). Use of uncoated pancreatic enzyme supplements, antibacterials, or H2 antagonists was not associated with longer survival. Breed, sex, age at diagnosis (≥4 years or > 4 years), and clinical signs at diagnosis also made no difference.   

Cobalamin (B12) and Folate levels

Texas A&M Guidelines  http://www.cvm.tamu.edu/gilab/assays/b12folate.shtml

     The normal range for Cobalamin (B12) is   252-908 ng/L .... low B12 levels are an indication that there is a B12 deficiency. It is absorbed in the distal small intestine (in the ileum). Low B12 levels are seen in dogs with EPI...  due to bacterial overgrowth in the upper small intestine, or disease affecting the distal small intestine.

(explanation of proximal small distal disease : "Low serum folate concentrations particularly draw attention to the possibility of dietary hypersensitivity since the proximal small intestine is exposed to the highest concentrations of food antigens. A hypersensitivity reaction causing mucosal damage is therefore most likely to result in folate malabsorption"http://www.revmedvet.com/2000/RMV151_559_563.pdf

simply put... A food intolerance could cause the low folate:

"Decreased serum folate can therefore be suggestive of damage to the proximal small intestine, as this is the main site for the absorption of dietary folate. There may be many causes of damage at this site, including dietary sensitivity which particularly affects the proximal small intestine where intraluminal dietary antigens are at their highest concentration e.g. gluten enteropathy in Irish setters. Alternative possible causes of proximal intestinal damage include idiopathic “inflammatory bowel disease” and lymphoma". http://www.ivis.org/journals/vetfocus/19_1/en/2.pdf  )

The normal range for Folate is  7.7 - 24.4 µg/L ... high folate levels are an indication of SIBO (small bacterial intestinal overgrowth). Values above the normal range are consistent with bacterial overgrowth in the upper small intestine. 

The following is the Texas A&M University - GI lab requirements for a B12 (and Folate) blood test. The absolute minimum SERUM requirements for a Cobalamin & Folate test is 400 µl (if doing a cTLI test add 500 µl). Any volume less than this can result in cancellation or incomplete testing. http://www.cvm.tamu.edu/gilab/assays/sampleguidelines.shtml        

Sample Handling Requirements:
For our tests, we require a 12 hour fasted serum sample. Please note that the serum MUST be separated from the blood clot and serum should be transferred into a new tube. The serum sample may be sent in a red top tube or any other leak-proof tube without additives as long as the serum is separated from the clot. Wrap the tube in enough absorbent material (e.g., paper towels) to absorb its entire contents in case of a spill, and place it in a plastic (i.e., ziploc) bag. Include at least one gel ice pack with your shipment to keep the sample at cool temperatures. Do not include ice cubes. Please note that lipemia and hemolysis may interfere with some test results, therefore we prefer a clear serum sample that is not lipemic or hemolytic to avoid inaccurate results.     
                            

Shipping Guidelines:
We recommend that you send your sample with Fed-Ex or UPS. This does not have to be sent overnight, The sample may be shipped 2nd day or Ground depending on when the actual assay is run (serum samples for TLI, PLI, cobalamin, and folate are stable for up to 2 weeks at room temperature). Please note that there is NO Saturday delivery at Texas A&M University. Note: Due to delivery procedures at such a large university, packages sent with the US Postal Service can often be delayed or even lost within departments. Please DO NOT use the US Postal Service as a carrier.

Please prepare your package:
1. Plastic, leak-proof sample tubes in a sealed plastic bag with enough absorbent material to soak entire contents in case of a spill.
2. Several frozen gel ice packs to account for longer transport or dry ice (Shipping dry ice has specific regulations; please contact your carrier for instructions)
3. Packing material for extra padding
4. Fill out the appropriate carrier’s shipping label with the address noted above and attach it to the box. We cannot pay shipping fees. Please note that the GI Lab does not accept packages marked “Bill Receiver”. Unfortunately, we must refuse these packages and we are not liable for any resultant delays. Somewhere on the outside of the package, as well as on the shipping label, please mark “Exempt Animal Specimen.” This is a requirement of the Texas Department of Transportation.

International Shipments:
In addition to the guidelines listed above, please include the following:
Please attach the following statement to the outside of the box. Also include a copy inside the box on official letterhead with a signature.
“This shipment contains only canine/feline serum for diagnostic testing. These samples are not contagious or infectious, and have not been derived from animals exposed to agents of agricultural concern. This shipment has no commercial value.”

 

Different types of B12 research / suggestions..........

http://veterinarycalendar.dvm360.com/avhc/article/articleDetail.jsp?id=724664&sk=&date=&pageID=3

 (Please visit the DMV360 website for this article / information... link provided above)

Cobalamin: Don't leave home without it (Proceedings)


CVC IN BALTIMORE PROCEEDINGS


Diagnosis of cobalamin deficiency

A definitive diagnosis of cobalamin deficiency can be challenging. Clinical signs are ultimately caused by cobalamin deficiency on a cellular level. However, the cellular cobalamin status is difficult to assess. Serum cobalamin concentration has been traditionally measured to help assess cobalamin status, but some patients with cobalamin deficiency on a cellular level do not always have severely decreased serum cobalamin concentrations. Thus, in order to avoid missing patients with cobalamin deficiency, cobalamin supplementation should be considered even when serum cobalamin concentration is low normal. Several assays for the measurement of serum concentrations of cobalamin in humans are available. In order to be used in dogs and cats, these assays designed for use in humans must be validated for use in dogs and cats. The GI Lab at Texas A&M University has recently analytically validated an automated chemiluminescence assay designed for the measurement of cobalamin concentration in humans for use in dogs and cats. A reference range for serum cobalamin concentration in dogs and cats was established using this assay (http://www.cvm.tamu.edu/gilab/assays/b12folate.shtml). It should be noted that reference ranges are not transferrable between labs and each lab should have their own reference range established.

Serum or urine methylmalonic acid (MMA) concentration can also be used as an indicator of cobalamin status. Cobalamin deficiency leads to accumulation of MMA and thus concentrations of MMA are often dramatically increased in the serum or urine of patients with cobalamin deficiency. Serum MMA concentrations have been shown to be increased in cats with cobalamin deficiency and have been shown to decrease with cobalamin supplementation. Also, recently dogs with severely decreased serum cobalamin concentrations were shown to have increased serum MMA concentrations. Interestingly, several dogs with low-normal serum cobalamin concentrations were also shown to have increased serum MMA concentrations, demonstrating that a severely decreased serum cobalamin concentration is not optimally sensitive for the diagnosis of cobalamin deficiency on a cellular level and that a cut-off value for cobalamin supplementation should be chosen that is in the low-normal reference range. This is especially true if one considers that cobalamin supplementation is minimally invasive, safe, and relatively cheap. As suggested by these data, measurement of serum MMA concentration may be a better diagnostic test for cobalamin deficiency than serum cobalamin concentration. However, measurement of MMA concentration in serum or urine is technically involved and expensive. Thus, MMA is currently not routinely assessed in patients evaluated for cobalamin deficiency.

Another way to assess cobalamin status is indirectly by use of a Schilling test. The Schilling test involves the oral administration of radioactively marked cobalamin that has been bound to an animal protein. However, to the author's knowledge the Schilling test has never been systematically evaluated in dogs or cats and is not practical for routine clinical practice.

Thus, the only routinely available diagnostic tool to assess cobalamin status in dogs and cats is serum cobalamin concentration, which should be evaluated in every dog and cat with chronic signs of gastrointestinal disease or with clinical signs compatible with cobalamin deficiency that cannot be attributed to other conditions (i.e., unexplained immunodeficiencies, anemias, neuropathies).

Cobalamin supplementation

Patients with severe cobalamin deficiency often do not respond to therapy of the underlying gastrointestinal disorder until cobalamin is supplemented. Unfortunately, only empirical suggestions are available concerning protocols for cobalamin supplementation in dogs or cats. However, there is no indication that over-supplementation of cobalamin leads to clinical disease. In humans, the standard route of cobalamin application is by parenteral administration. This is because cobalamin deficiency has been shown to lead to cobalamin malabsorption in the ileum. However, there are recent data that would suggest that with certain forms of cobalamin deficiency, oral or nasal supplementation may be efficacious. There are no such data for dogs or cats and the data in humans is controversial. Thus, currently, the recommendation is to supplement cobalamin in veterinary patients by subcutaneous injection. The most common form of cobalamin used for supplementation is cyanocobalamin, but hydroxocobalamin can also be used. The author empirically uses the following dosing schedule: 150-250 µg per injection in cats, 250-1500 µg per injection in dogs; SC q 7 days for 6 weeks, then q 14 days for 6 weeks, then q 30 days for one injection, then reevaluate serum cobalamin concentration one month later. If the underlying disease process has resolved and cobalamin body stores have been replenished, serum cobalamin concentration should be supranormal at the time of re-evaluation. However, if serum cobalamin concentration is in the normal range, treatment should be continued at least monthly and the owner should be warned that clinical signs may recur sometime in the future. Finally, if serum cobalamin concentration at the time of recheck is subnormal, further work-up is required to definitively diagnose the underlying disease process and cobalamin supplementation should be continued weekly or bi-weekly. In a recent study cats with chronic gastrointestinal disease that had failed therapy and were shown to have cobalamin deficiency quickly gained weight after initiation of cobalamin supplementation.

It is also interesting to note that the recommended dose for cobalamin supplementation in humans by far exceeds what is believed to be the physiologic cobalamin requirement in humans. Thus, there is speculation that the beneficial responses of cobalamin supplementation in human patients with cobalamin deficiency may at least in part be due to pharmacologic effects of cobalamin.

ANECDOTAL "Other B12" OBSERVATIONS ...

The following are ANECDOTAL observations in using other forms of B12

These B12 observations ARE NOT scientifically proven veterinarian methods recommended to manage insufficient B12 levels in EPI dogs...... however...... these methods have been observed to work in many cases with epi4dogs forum members with EPI dogs that need to manage their B12 levels. 

Our hope is that our "anecdotal" observations might be enough evidence for the veterinarian research community to do clinical trials with these other B12 management techniques to support (or not) our observations.

 

1. Many EPI owners have recently found success with "maintaining"  B12 levels (after a regimen of B12 injections) with B12 pills that has the "intrinsic factor" included in the product. This product is "Intrinsi B12/Folate" and uses the cyanocobalamin form of B12 manufactured by Metagenics: http://www.metagenics.com/products/detail.asp?pid=163

Approximate cost is $46 per bottle of 180 tablets. Dosage depends on the individual dog.... some take 1 pill daily, some 1/2 pill, some take 1 pill 3 times a week.

PLEASE discuss this product/option with your vet. This may or may not be an option for you and your dog. Your vet will need to test your dog's B12 level before and after to test for effectiveness and recommended dose.

 

2.  More and more members are now using another B12 pill product with the "intrinsic factor" included that was initially called "Trinfac-B" but is now called "PET Factor B-12" with Folate and Methyl B12 produced by Wonder Laboratories  ... at 1/3 the cost of Metagenics that has been observed to give excellent results as an a B12 alternative for EPI dogs. 
http://www.wonderlabs.com/itemleft.php?itemnum=K9688

Approximate cost is $13 per bottle of 90 capsules. Dosage depends on the individual dog.... some take 1 pill daily, some take 2 pills daily,  some 1/2 pill, some take 1 pill 3 times a week.

PLEASE discuss this product/option with your vet. This may or may not be an option for you and your dog. Your vet will need to test your dog's B12 level before and after to test for effectiveness and recommended dose. 

 

2a. There is now available in the UK a comparable 1000mcg Methycobalamin B12 capsule that also includes the 40mg of the Intrinsic Factor, like the USA Wonderlabs "PET Factor B-12". Please feel free to check out the UK version of B12/Intrinsic Factor capsule at Chemeyes, LLC   http://www.chemeyes.co.uk/ 


3.  Another observation is that "some"  EPI  cases (dogs) with low B12 can be maintained with sublingual methylcobalamin B12 tabs. 

PLEASE discuss these products/option with your vet. These may or may not be an option for you and your dog. Your vet will need to test your dog's B12 level before and after to test for effectiveness and recommended dose. 

"Possible" warning with Folate, B6  & B12 and Kidney disease 

December 16, 2013

 

As most of you know, i browse through a lot of research... so when something catches my eye that i think "might" be interesting to our group, i post about it.

 

Well.... i was just made aware of a Folate, B6 and B12 issue in one human study (published in JAMA 2010) that even caught the researchers off-guard! 

 

"Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy (kidney disease caused by diabetes)
A Randomized Controlled Trial"

http://jama.jamanetwork.com/article.aspx?articleid=185758

so please be in mind, that:

 

  • this is a human study not a dog study so it may not be relevant
  • they want to do MORE studies since this result has never happened before....

 

 However, the reason why i think it is important to share here is because not only did i find it interesting.... but also i wanted to share that sometimes, no matter how much science / researchers  think they know about something, sometimes new research or even new technology comes along and changes everything.... so we really need to try to stay current on our information and we must always try to remember that nothing is absolute. 

 

Anyway,  the scoop of the article is that these researchers were trying to determine if  B-vitamin therapy can

 

  • (1) slow progression of diabetic nephropathy and
  • (2) prevent vascular complications.

  

"Since  B-vitamin therapy has been shown to lower the plasma concentration of homocysteine and improve endothelial function"... they assumed that the "B-vitamin therapy would slow the progression of diabetic nephropathy and prevent vascular events".

 

"Participants were randomized 1:1 to receive a single tablet of B vitamins that contained 2.5 mg/d of folic acid, 25 mg/d of vitamin B6, and 1 mg/d of vitamin B12, or a matching placebo".

 

 

Conclusion Among patients with diabetic nephropathy, high doses of B vitamins compared with placebo resulted in a greater decrease in GFR and an increase in vascular events.

The  increased vascular events (MI, stroke, revascularization, etc.)  "was double that in the placebo group"

 

Because  these vitamins are water-soluble and renally excreted, vitamin toxicity may be more of a concern in patients with impaired renal function. (kidney disease)


"Our trial is the first study to our knowledge to show significant detrimental effects from pharmacological doses of B vitamins (folic acid, vitamin B6, and vitamin B12)."

 

This study was done on patients with diabetic nephropathy (kidney disease) .

 

My take away from this article is that "IF" your dog has a kidney condition.... no matter how much we have been told that B vitamins are safe / water soluble and any extra is just peed out........ that for those battling a kidney condition.... PLEASE talk to your vet first about how much B vitamins (folate, B6 and B12) your dog should or shouldn't be getting..... since kidneys are where these extra vitamins are excreted and if they are impaired because of kidney disease.... this process may not be functioning properly enough to get rid of these extra vitamins.

wondering about FOLATE levels in B12 in supplementation ???

A nice explanation about the folate levels in B12 supplementation from one of our members, Kathy:

 

Kathy and Ted
Member
Posts: 2515

I will explain this as best I can.

Folate is Vitamin B9. High folate levels are indicative of low B12 because the body needs B12 to change folate ( B9) into its active form. Because the B12 is low the folate can be high. Talking the oral B12 with folate will not raise the folate level because now the two vitamins, B12 and B9 will be working together,  the B12 will utilize the B9. Folic acid (B9) must be present for the proper use of B12.

Hope this makes sense.

 

B12 availability

If you are interested in giving B12 injections at home, ask your vet to show you how to do it properly. Ask your vet if you can purchase the B12 serum from them... or....you can purchase it from your pharmacist, or on-line.

http://www.b12-shot.com/ 

B12-Shot.com is located in British Columbia, Canada. You can simply place your order online, and they will ship to the States. 

Rubramin PC® (Cyanocobalamin Injection) contains cyanocobalamin (vitamin B12) in a clear, red, sterile, nonpyrogenic, aqueous solution in a potency of 1000 mcg/mL (cobalt: 40 mcg/mL) for intramuscular use. Each mL of solution also contains 10 mg benzyl alcohol as a preservative and sodium chloride for isotonicity; pH has been adjusted between 4.5 and 7.0 with sodium hydroxide or hydrochloric acid.

Cyanocobalamin is very hygroscopic in the anhydrous form, and sparingly soluble in water (1:80). The vitamin B12 coenzymes are very unstable in light.

Rubramin PC® - Clinical Pharmcaology 

-----------------------------------------

B12 (Cobalamin) Serum now available in Australia (April 2013):

There is now a B12 injectable liquid available in Australia which can be purchased from various pet stores and online sources. Many vets that give your EPI dog a B12 injection will already be using this particular brand and product - It is made by Troy and its composition is Cyanocobalamin 1.0mg/mL. It is not a multi-plex B12 or other strain of the vitamin.

Some dogs may require ongoing injections (weekly, fortnightly or monthly) if they are unable to keep a high enough B12 level utilising Wonderlabs Trinfac B12 pill. Needles and syringes can be purchased directly from your vet or from a local pharmacy, as well as the needle disposal bin for a small fee of under $10.

A few online sources of Vitamin B12 are:

http://www.mypetwarehouse.com.au/TROY-VITAMIN-B12-100ML-p-14619

http://www.thevetshed.com.au/shop/horse-products/supplements/troy-b12-injection/130620

http://www.vetnpetdirect.com.au/TROYB12#.UXCkA6Kj3-s

Be sure to discuss this avenue with your vet if this is something you would like to partake in.

Depending on where you source the needles and syringes from, you are looking at approximately $40-$50 which will include the B12 liquid, needles, syringes and the needle disposal bin. Prices are subject to change depending on where you make the purchases from and will vary from state to state.

As per Texas A&M Gastroenterology Lab posted on  http://www.epi4dogs.com/b12.htm the recommended dosages of Cobalamin for EPI dogs and cats is as follows:

Animal Bodyweight Range (Dose/injection)

·         Cats, dogs up to 5 kg (10 lb) 250 µg (0.25mL)

·         Dogs, 5-15kg (10-30 lb) 400 µg (0.4mL)

·         Dogs, 15-30 kg (30-65 lb) 800 µg (0.8mL)

·         Dogs, 30-45 kg (65-100 lb) 1200 µg (1.2mL)

·         Dogs above 45 kg (100 lb) 1500 µg (1.5mL) 

 

B12 (Cobalamin) Availability in Canada 

 B12 Injectible Serum from Alveda Pharma soon to be available (Aug 2013) at http://thepetpharmacy.ca/ 

About that "Intrinsic Factor" .................

 

Veterinarian clinical studies recommend generic B12 serum injections to supplement an EPI dog with low B12 levels. When given a B12 (simple Cyanocobalamin serum) injection, the B12 goes right into the blood stream. If B12 is digested, it does not seem to be adequately absorbed unless given in very high doses, which may or may not work with some dogs, or what does seem to work with most EPI dogs are special B12 pills made with methycobalamin version of B12 and included is 40 mg of Intrinsic Factor (which is used to transport the B12 from the digestive system into the blood stream) . Although technically the Intrinsic Factor delivery system should not typically be destroyed by the EPI condition....... it appears that when given these B12 pills with the Intrinsic Factor, the B12 is better absorbed by the individual. So.... it may be possible that with EPI maybe in some cases or to some degree there is a problem with the intrinsic factor delivery system... or else something else can be attributed to why these pills work well... maybe it is using the Methycobalamin version of b12 vs. Cyanocobalamin.  We just don't know why these special "Trinfac or Pet Factor B12 pills made with Methycobalamin and Intrinsic Factor appears to work so well with these EPI cases, but they do.

So, what we have observed here on epi4dogs and at k9-EPI Global is that, although there is no clinically controlled research to back up our claims, many EPI pet owners have used special B12 capsules that have the Intrinsic Factor included in the contents of Methycobalamin B12 (which is more potent than Cyanocobalamin) and when their dogs with low B12 are re-tested (via Cobalamin "B12" blood test) after being on these special B12 capsules, their B12 levels were greatly improved.  This Methylcobalamin B12 with the Intrinsic Factor is  available in the USA at Wonderlabs "PET Factor B12" http://www.wonderlabs.com/itemleft.php?itemnum=K9688  ...or  "Trinfac" made for humans, but it is the exact same thing http://www.wonderlabs.com/itemleft.php?itemnum=6881 but now, thanks to Chemeyes, LLC  in the UK for accommodating epi4dogs, Chemeyes http://www.chemeyes.co.uk/now carries a Trinfac B product (capsule) that is of the same composition as the Wonderlabs "PET Factor B12"called the "Trinfac "product http://www.chemeyes.co.uk/#!trinfac-b/czna .   (see below)

UK

Chemeyes, LLC "Trinfac B" with Intrinsic Factor"   http://www.chemeyes.co.uk/#!trinfac-b/czna or you can email Cameron directly at: [email protected]     or     call him at: 0845 838 1367

Vitamin B12 as methylcobalamine: 1000mcg
Folate: 800mcg
Intrinsic Factor: 40mg

 

USA

Wonderlabs "PET Factor B-12" (formerly TRINFAC-B)" can be purchased at:

http://www.wonderlabs.com/itemleft.php?itemnum=K9688 

Or.... you can purchase the human version (same stuff) called Trinfac:

http://www.wonderlabs.com/itemleft.php?itemnum=6881 

Folate 800mcg
Vitamin B12 (Methycobalamin) 1000mcg
Intrinsic Factor 40mg

 Wonderlabs B12 with intrinsic factor included products such as B12 Trinfac and PET Factor B12 are highly recommended by Epi4Dogs for use as your EPI pet's B12 supplementation. To-date, with approximately 1000+ EPI patients on the Wonderlabs B12 products, we estimate a positive result of about 95% with this product. Currently Wonderlabs is now interested in your feedback if using their B12 product(s). By giving them your feedback, not only will you assist Wonderlabs, but this data can be compiled to further assist EPI B12 research.

To submit feedback for Wonderlabs Pet Factor, click here:  https://www.wonderlabs.com/itemleft.php?itemnum=K96882

To submit feedback for Wonderlabs B12 Trinfac, click here:  https://www.wonderlabs.com/itemleft.php?itemnum=6881

Understanding B12 (references)

Very little evidence-based information about cobalamin (B12) supplementation in dogs and cats is available.
Hence, the listing below of human studies on B12.
Understanding B12

http://www.aafp.org/afp/2003/0301/p979.html#afp20030301p979-b9 

http://ods.od.nih.gov/factsheets/vitaminb12-HealthProfessional/

References

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