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A Silent Epidemic with Serious Consequences—What You Need to Know about B12 Deficiency

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Reviewed by Chris Masterjohn, PhD

This tired man rubbing his eyes may be experiencing B12 deficiency.
Fatigue is a common symptom of B12 deficiency.

What do all of these chronic diseases have in common?

  • Alzheimer’s, dementia, cognitive decline, and memory loss (collectively referred to as “aging”)
  • Multiple sclerosis (MS) and other neurological disorders
  • Mental illnesses like depression, anxiety, bipolar disorder, and psychosis
  • Cardiovascular disease
  • Learning or developmental disorders in kids
  • Autism spectrum disorder
  • Autoimmune disease and immune dysregulation
  • Cancer
  • Male and female infertility

Answer: Their signs and symptoms can all be mimicked by a vitamin B12 deficiency.

An Invisible Epidemic

B12 deficiency isn’t a bizarre, mysterious disease. It’s written about in every medical textbook, and its causes and effects are well-established in the scientific literature.

However, the condition is far more common than most healthcare practitioners and the general public realize. Data from a Tufts University study suggests that 40 percent of people between the ages of 26 and 83 have plasma B12 levels in the low normal range—a range at which many experience neurological symptoms. Nine percent had an outright nutrient deficiency, and 16 percent exhibited “near deficiency.” Most surprising to the researchers was the fact that low B12 levels were as common in younger people as they were in the elderly. (1)

That said, this type of deficiency has been estimated to affect about 40 percent of people over 60 years of age. It’s entirely possible that at least some of the symptoms we attribute to “normal” aging—such as memory loss, cognitive decline, and decreased mobility—are at least in part caused by a deficiency.

Why Is It Underdiagnosed?

B12 deficiency is significantly underdiagnosed for two reasons. First, it’s not routinely tested by most physicians. Second, the low end of the laboratory reference range is too low.

This is why most studies underestimate true levels of deficiency. Many deficient people have so-called “normal” levels of B12.

Yet, it is well-established in the scientific literature that people with B12 levels between 200 pg/mL and 350 pg/mL—levels considered “normal” in the U.S.—have clear vitamin deficiency symptoms. (2) Experts who specialize in the diagnosis and treatment of a deficiency, like Sally Pacholok, R.N., and Jeffrey Stuart, D.O., suggest treating all patients that are symptomatic and have B12 levels less than 450 pg/mL. (3) They also recommend treating patients who show normal B12 levels but also have elevated urinary methylmalonic acid (MMA), homocysteine, or holotranscobalamin, which are other markers of a deficiency in vitamin B12.

B12 deficiency can mimic the signs of Alzheimer’s, dementia, multiple sclerosis, and several mental illnesses. Find out what this vitamin does and learn how to treat a deficiency. #B12 #B12deficiency #cognitivedecline

In Japan and Europe, the lower limit for B12 is between 500 and 550 pg/mL. Those levels are associated with psychological and behavioral symptoms, such as:

  • Cognitive decline
  • Dementia
  • Memory loss (4)

Some experts have speculated that the acceptance of higher levels as normal in Japan and the willingness to treat levels considered “normal” in the U.S. explain the low rates of Alzheimer’s and dementia in that country.

What Is Vitamin B12 and Why Do You Need It?

Vitamin B12 works together with folate in the synthesis of DNA and red blood cells. It’s also involved in the production of the myelin sheath around the nerves and the conduction of nerve impulses. You can think of the brain and the nervous system as a big tangle of wires. Myelin is the insulation that protects those wires and helps them to conduct messages.

Severe B12 deficiency in conditions like pernicious anemia (an autoimmune condition where the body destroys intrinsic factor, a protein necessary for the absorption of the vitamin) used to be fatal until scientists figured out death could be prevented by feeding patients raw liver, which contains high amounts of B12. But anemia is the final stage of a deficiency. Long before anemia sets in, deficient patients will experience several other problems, including fatigue, lethargy, weakness, memory loss, and neurological and psychiatric problems.

The Stages of a Deficiency

B12 deficiency occurs in four stages, beginning with declining blood levels of the vitamin (stage I), progressing to low cellular concentrations of the vitamin (stage II), an increased blood level of homocysteine and a decreased rate of DNA synthesis (stage III), and finally, macrocytic anemia (stage IV). (5)

Common B12 Deficiency Symptoms

The signs can look like the symptoms of several other serious disorders, and the neurological effects of low B12 can be especially troubling.

Here are some of the most common vitamin B12 deficiency symptoms:

  • Tingling or numbness in the hands and feet
  • Brain fog, confusion, and memory problems
  • Depression
  • Premature aging
  • Cognitive decline
  • Anemia
  • Weakness
  • Fatigue
  • Reduced appetite and weight loss
  • Constipation
  • Trouble balancing (6)

Children can also show symptoms, including developmental issues and learning disabilities if their B12 levels are too low.

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Why Is It So Common?

The absorption of B12 is complex and involves several steps—any of which can go wrong. Any of the following can cause B12 malabsorption:

  • Intestinal dysbiosis
  • Leaky gut and gut inflammation
  • Atrophic gastritis or hypochlorhydria, or low stomach acid
  • Pernicious anemia
  • Medications, especially proton pump inhibitors (PPIs) and other acid-suppressing drugs
  • Alcohol
  • Exposure to nitrous oxide, during either surgery or recreational use

This explains why a deficiency can occur even in people eating large amounts of B12-containing animal products. In fact, many of my patients that are B12 deficient are following a Paleo diet where they eat meat two or three times daily.

Who Is at Risk for a Deficiency?

In general, the following groups are at greatest risk for a deficiency:

  • Vegetarians and vegans
  • People aged 60 or over
  • People who regularly use PPIs or acid-suppressing drugs
  • People on diabetes drugs like metformin
  • People with Crohn’s disease, ulcerative colitis, celiac, or IBS
  • Women with a history of infertility and miscarriage

Note to Vegetarians and Vegans: B12 Is Found Only in Animal Products

You cannot get B12 from plant-based sources. This vitamin is only found in animal products. That’s why vegetarians and vegans need to know the signs of deficiency—and the steps necessary to fix the problem.

B12 is the only vitamin that contains a trace element (cobalt), which is why it’s called cobalamin. Cobalamin is produced in the gut of animals. It’s the only vitamin we can’t obtain from plants or sunlight. Plants don’t need B12, so they don’t store it.

A common myth among vegetarians and vegans is that it’s possible to get B12 from plant sources like:

  • Fermented soy
  • Spirulina
  • Brewers yeast

However, plant foods said to contain B12 actually contain B12 analogs called cobamides that block the intake of and increase the need for true B12. (7) That explains why studies consistently demonstrate that up to 50 percent of long-term vegetarians and 80 percent of vegans are deficient in B12. (8, 9)

Seaweed is another commonly cited plant source of B12, but this idea is controversial. Research indicates that there may be important differences in dried versus raw purple nori; namely, raw nori may be a good source of B12, while dried nori may not be. One study indicated that the drying process used for seaweed creates B12 analogs, making it a poor source of the vitamin, while animal research suggests that dried nori can correct a B12 deficiency. (10, 11) Seaweed may provide B12, but it’s not clear if those benefits are negated when that seaweed is dried. I recommend caution for that reason.

The Impact of a Deficiency on Children

The effects of B12 deficiency on kids are especially alarming. Studies have shown that kids raised until age six on a vegan diet are still B12 deficient even years after they start eating at least some animal products. In one study, the researchers found an association between a child’s B12 status and their performance on testing measuring:

  • Spatial ability
  • Fluid intelligence
  • Short-term memory

Researchers found that formerly vegan children scored lower than their omnivorous counterparts in each area. (12)

The deficit in fluid intelligence is particularly troubling, the researchers said, because this area impacts a child’s ability to reason, work through complex problems, learn, and engage in abstract thinking. Defects in any of these areas could have long-term consequences for kids.

I recognize that there are many reasons why people choose to eat the way they do, and I respect people’s right to make their own choices. I also know that, like all parents, vegetarians and vegans want the best for their children. This is why it’s absolutely crucial for those that abstain from animal products to understand that there are no plant sources of B12 and that all vegans and most vegetarians should supplement with B12.

This is especially important for vegetarian or vegan children or pregnant women, whose need for B12 is even greater. If you’re not willing to take a dietary supplement, it may be time to think twice about your vegetarian or vegan diet.

How to Treat a Deficiency

One of the greatest tragedies of the B12 epidemic is that diagnosis and treatment are relatively easy and cheap—especially when compared to the treatment patients will need if they’re in a late stage of deficiency. A B12 test can be performed by any laboratory, and it should be covered by insurance. If you don’t have insurance, you can order it yourself from a lab like DirectLabs.com.

As always, adequate treatment depends on the underlying mechanism causing the problem. People with pernicious anemia or inflammatory gut disorders like Crohn’s disease are likely to have impaired absorption for their entire lives and will likely require B12 injections or high-dose oral cobalamin indefinitely. This may also be true for those with a severe deficiency that’s causing neurological symptoms.

Typically in the past, most B12 experts recommended injections over high-dose oral cobalamin for people with pernicious anemia and an advanced deficiency involving neurological symptoms. However, recent studies have suggested that high-dose oral or nasal administration may be as effective as injections for those with B12 malabsorption problems. (13, 14)

Try Supplementing

Cyanocobalamin is the most frequently used form of B12 supplementation in the U.S. But recent evidence suggests that hydroxocobalamin (frequently used in Europe) is superior to cyanocobalamin, and methylcobalamin may be superior to both—especially for neurological disease.

Japanese studies indicate that methylcobalamin is even more effective in treating neurological symptoms and that it may be better absorbed because it bypasses several potential problems in the B12 absorption cycle. (15, 16) On top of that, methylcobalamin provides the body with methyl groups that play a role in various biological processes important to overall health.

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Chris Kresser in kitchen

Change Your Diet

Nourishing your body through whole food is the best way to get the vitamins and nutrients you need. If you’re low on B12, try eating some vitamin-rich foods like:

Eating other kinds of seafood, like octopus, fish eggs, lobster, and crab, can also help you attain normal B12 levels. If you’re seafood-averse, you can also get this vitamin from:

  • Lamb
  • Beef
  • Eggs
  • Cheese

It’s important to note, though, that the amount of B12 in these foods is nowhere near as high as the levels in shellfish and organ meats.

What to Do if You’re Experiencing Vitamin B12 Deficiency Symptoms

If you suspect you have a deficiency, the first step is to get tested. You need an accurate baseline to work from.

If you are B12 deficient, the next step is to identify the mechanism causing the deficiency. You’ll probably need help from a medical practitioner for this part. Once the mechanism is identified, the appropriate form (injection, oral, sublingual, or nasal) of supplementation, the dose, and the length of treatment can be selected.

So, next time you or someone you know is “having a senior moment,” remember: It might not be “just aging.” It could be B12 deficiency.

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1,962 Comments

Join the conversation

  1. Chris Kresser,

    I was reading a lot of information about the absorption of B12. Eight years ago, I started having numbness and tingling in my feet, feeling tired and having trouble with memory. I saw about 4 neurologists including one at Cleveland clinic. I had a few MRI’s, spinal and numerous blood tests.
    No one could find out what was causing this. They told me to go back to my regular physician.
    Two years later a family member told an internal doctor about me. I went to see him and I had another MRI and blood tests and it was was not MS, which none of the MRI’s showed MS, but he found I had a VERY SEVERE B12 deficiency. My level was an extremely low 41. Of course within these past 2 years before he found it was my B12, my conditions were getting worse. He started me on B12 injections regimin which made my level go up but unfortunately, I had permanent nerve damage.

    My balance is very bad, I have numbness and tingling from the waist down extreme stiffness and spasms in my legs and feet. And in my hand too. I use the Nasal spray now which my level has been in the 700 range which my dr, is satisfied. But now I have to use a cane, or a rollater, and in the house I just hold onto things. I’m on baclofen and valium for stiffness and spasms. I’m unable to work at any job.
    I was evaluated at the Mellon center in Cleveland clinic. I’ve been denied soc. security disability and ssi
    each time I’ve applied. Now since it has been 8 years later, I still haven’t fully accepted being disabled but everyday I try my best to get things accomplished but at a slower pace. I wish somehow or way I could get my message out to people how important B12 is.

    I just wanted to share my story with you.
    If you could email me back to let me know that you received my message.

    Thank you.

    Judy

    • Judy,
      Your story is an indictment of our medical system. If one of those doctors had given you a B12 test earlier on, think of the misery and ill health you might have been spared. And all that expense spared as well.

      It’s probable you’re still not getting optimal treatment. In some people, the serum can show an adequate level of B12, but the CNS can still be grossly deficient in B12. Your symptoms suggest you have subacute combined degeneration (SCD). Nasal sprays are not an adequate treatment for SCD.

      Freddd (see his prior posts) has made a remarkable recovery from his SCD based on a protocol of his own devising. It’s a very long road, but you too might be able to experience some recovery. Greg’s company, Mentor Consulting, makes a transdermal product called Red B12, that I think is a much better treatment for B12 deficiency diseases. He gave his email previously: [email protected]. Some people have had a recovery previously thought impossible via rigorous application of Red B12. It is possible to replete your CNS B12, and sometimes seemingly permanent nerve damage can be reversed.

      • Hi Judyj,
        Thank you for sharing your remarkable story with the group. As Lynn has said it is a remarkable indictment of the general medical system. Every time I read a story like this I am amazed that vitamin B12 deficiency was missed for so long, particularly considering your neuronal symptoms. As Lynn has said it is such an easy thing to at least try early on and the test for deficiency is so cheap and easy. I am sure that you are now well and truly around the literature on VB12 deficiency. I have attempted to add some more information on my web-site http://www.vitaminb12deficiency.net.au . My reading of the literature suggests that it may take months or even years to reverse the neuronal damage, during this time it is essential that you keep your levels up. Once the damage has been done to the neurones, they can recover, but it is very slow. The lipids and myelin basic protein have a very slow turnover time, so these have to be gradually replaced for you to get normal function. In this regard Freddd’s story is relevant as by persisting he gradually got better. Many studies in the literature appear to not take this slow turn over into consideration and finish too early.
        As Lynn has also eluded to it is important to get the levels in the CNS up again and several studies have shown that this does not happen with either high dose oral or with sprays or sublinguals, or if it does it is very, very slow, which may explain why it took Freddd so long. It is for this reason that we designed the transdermal product that Lynn eluded to.
        Apart from the treatment, one of the most important things to also identify is why you became deficient, as this also has a massive implication later on. Evidence suggests that if you are severely vitamin B12 deficient you also have trouble with intestinal absorption of most of your water soluble vitamins, so it would be useful for you to have your levels of these checked.
        So be patient, you are on a long road, but at least you have turned the corner. You will find that this group is very supportive if you have further questions.

        • Hi Greg,

          I was so happy that I finally got a response from somebody. As there are support groups for MS patients there is nothing for people like me and joining this might help me with my depression sometimes. I will read the link you gave me. I will keep you up to date on things.

          Thanks!

  2. For people in general that have B12 less than 100 – what was the prognosis? How are you guys feeling and how long did it take to start feeling better? I feel like crap and my B12 is 84 and i have been on shots for 8 weeks now (once a week) and i still feel all the numbing/tingling and muscle spasms! Its like the stock market – one week i am great, another week i feel terrible. Hope its an improving trend though…

    Please HELP!

    • Boy 84 is REALLY LOW. IT is going to take you some time to get up over 300, so be patient. Do you know what type of VB12 you are being injected with CN-Cbl, OHCbl, AdoCbl or MeCbl. My guess would be CN-Cbl. If you are getting a small boost following injection that is a good sign. Trouble with injections is that they give a huge amount of VB12, but the effect is only transient. Many discussions with this on the site if you require further info, but just ask if you want more information. There are many people on the site who are only too willing to help.

      • Greg – thanks much! I feel great a day after the injection…then i started feeling better days on at a time, then a week at a time. Shortly there after, i started working out again and now i feel like crap – almost like back to square one. Did another blood draw to check my new levels. Waiting on results. I dont know if my withdrawal is more than what i am injecting into my system. Do you know if injections once a week is good enough? I am on the cyanocobalamin B12…forget the actual name. I also take the lozenges nightly. Can you OD on the lozenges or B12 in general?

        thanks again to the entire community in general…we shall overcome!

        • Hi GD, So some good news there. At least the VB12 is having some effect as it brings you back “from the grave”. So it now looks like you are in the “overdoing it” category. With your injections, you get a big boost all at once, but it will take you possibly years of injections to get your levels up to say >400 so that they will stay up. Some people with uptake problems need injections for life, so it shows that the injections won’t last and don’t necessarily completely restock the system. So as you try to get your levels up and maintain them you will feel a boost but it will only be transient as your liver stores (and arguably your CNS stores) won’t be “filled up”.
          Don’t think many people on the group like CN-Cbl, it is a provitamin and is not converted to AdoCbl and MeCbl as effectively as either HO-Cbl or giving the mix of Me/AdoCbl.
          As for the lozengers, there is much better technology out there, and many people complain of the effects on eroding your teeth, etc with lozenges.
          Over-dosing, well they have injected 5 gm HOCbl iv for cyanide poisoning, so not very likely with your doses.

          • Greg, don’t you think that the RedB12 would be a better solution? Shouldn’t it give a better release for GD?

            • Madge,
              Greg has shared much with me about the biochemistry of B12 and why using a transdermal application such as Red B12, or subcutaneous injections, provides a sustained release of B12 into the body, and thus is far superior to the peaks and troughs experienced from IM injections of B12. I agree with you that GD would be better off with Red B12, but I think Greg is being careful about not overpromoting Red B12.

              GD,
              I have been using Red B12 from transdermoil.com for around three months, after using sublingual methylB12 for several years. I can tell a noticeable increase in energy and upbeat mood lately. Since I’m taking other supplements as well, it’s hard to attribute that energy strictly to Red B12, but the timing makes me think it’s largely responsible. I am one of those people whose teeth were getting etched from sublingual mB12. With MTHFR, CUBN, and FUT2 mutations, I will be on methyl B12 for life, so I’m grateful that a transdermal application method that gets the B12 into the cellular level is now available.

              If you have MTHFR, FUT2, or CUBN mutations, the cyanoB12 isn’t going to do you much good. You will need either hydroxyB12 or methylB12. There are research articles out there that I’ve read with results that say cyanoB12 doesn’t work as well for anyone, even for people without those mutations. CyanoB12 injections are convenient to obtain and cheaper, but for many people cyanoB12 just don’t do the job. Subcutaneous injections are better than IM for B12, but I think Red B12 is even better. No injection needed.

              • I totally agree with Lynn (and no I don’t like to push the product – guess I never was a salesperson).
                GD and Madge, what is also very important (and you can see that from Lynn’s comments) is why GD is deficient.Do you know if it is diet, disease or genetics? It is very important to determine this as it makes a lot of difference down the track. Mind you, if you look at all the possible neuronal problems of being deficient in VB12, I for one would also be taking VB12 for life (and for neurones).

  3. I was feeing fluish the past 3 day with low grade fever, ear ache, tiredness, sinus pain, loss of appetite. The last 2 days have had pins and needle feeing in my arms and legs more just in my arms today and just got some red blemishes on my but. I went to the doc yesterday and he said it was just the flu. don’t have flu symptoms as bad today just pins and needles

    I have been on a dairy an gluten free diet off and on since July, trying my best to stay off it but its hard.

    I think my calcium is low ad could my b12 be also. I also have 1 petechial on my elbow and one on my chest.

    scared I have cancer.

    • Hi Eliot,
      Great point about the deficiency in cattle and sheep. This is particularly a problem in areas of low cobalt in the soil, and hence the bacteria in the gut of these animals can’t make sufficient vitamin B12 (as no cobalt), hence the cattle or sheep become deficient. This is also an example of what we can learn from these animals as far as vitamin B12 deficiency and its consequences, which are actually quite similar to the human story. Thus in pregnant animals, the VB12 levels in the foetus are a reflection of the mothers. Thus if the mother is deficient, so too is the foetus and neonate. After birth, the levels of VB12 in both mothers and neonate drop dramatically and then slowly climb back. This also happens in humans. Why on earth mothers are not told this escapes me.
      The next point is that the symptoms of deficieny in the neonatal animals is similar to humans, failure to thrive, developmental delay etc, etc. Following up further in the literature you also find in animals (as in humans) those that are deficient have poor differentiation in the gut, and have compromised immune systems leading to an inability to maintain the barrier function in the intestine with resultant gastro-intestinal tract problems. If you follow the thread of many of the discussions even on this web-site, it is a very common finding in humans who are VB12 deficient. I would urge all of you who are considering to have a diet low in vitamin B12 to supplement, if only for the sake of the unborn and new-born child. They do not deserve to be developmentally delayed, pre-term and/or have microencephaly (small heads).
      In short there is much that we can learn from livestock animals as far as the consequences of cobalt/vitamin B12 deficiency.
      I thank you for making us aware of the area, which I for one had temporarily neglected.

  4. I am 22 years old, I was diagnosed with serve B12 deficiency this year. My symptoms started when I was in grade 9 however. I was sitting at my desk when my fingers on my right hand started to feel tingly. The feeling began to slowly move up my right arm, as well as my left. The second set of symptoms I had followed a year later. While showering I became VERY disoriented, dizzy, had tunnel vision, and collapsed. My most recent symptoms, I was speaking to a friend of mine when my head started to feel… airey. I became very dizzy, lost my vision, and in my head all could hear was a household fire alarm going off. I then blacked out while standing and my legs gave out. Luckily my boyfriend was there to break my fall. I had neglected to attend my doctor’s office for regular shots.

  5. Hi,
    Can anyone advise me on this: I have pronounced peripheral neuropathy plus significant weakness down my right side – to the extent of walking with crutches now. No gross neurology on MRI scan, but longstanding M.E. I guessed at B12 deficiency and went for a test. After the test I started just taking the sublingual B12 myself while waiting for the results. This helped a bit -but the test came back very high! Over 2000. This has been consistent over the past year. I just came off supplements for 3 weeks to get retested, and my symptoms have really deteriorated as a result – but the test is still sky-high. I can’t get injections because my level is high, and the GP and neurologist have nothing to offer.
    So, my question – why could my B12 be really high, with deficiency symptoms that improve with B12?? And what do I do now? I asked for an active B12 test but the lab refused it (English National Health System).
    Thanks for any help,
    Leilani

    • Hi Leilani,
      There will be many others who have contributed to this discussion over the years who have had similar, misleadingly high vitamin B12 levels, who might re-affirm this on the forum. By my records, over half the people who have had similar problems have had levels over 1000 and also have had troubles with their doctors prescribing vitamin B12.
      Looking at the literature this paradoxical effect, it is not particularly well dealt with, but it also probably confounds, or affects many studies looking at vitamin B12 deficiency, as if there are people with symptoms such as yours and yet have high vitamin B12 levels, they will say the effect/symptom has nothing to do with vitamin B12 deficiency.
      So what can be going on. My guess (as no-one appears to have done the study) is that either you have a very high circulating level of haptocorin (a vitamin B12 binding protein), which keeps the vitamin B12 in serum, but the B12 is not available to nerves etc, so you look as if you have good vitamin B12, but in fact you don’t (yes your active B12 test would tell you this). Another possibility is that you have a bacterial over-load in your intestine that is making defective B12, which once again shows up as positive on the B12 test (once again the active B12 test may tell you this). There is also an increasing amount of evidence that suggests that in chronic inflammation there is continual synthesis of nitric oxide, which reacts with vitamin B12 making NO-VB12, which also is not active, but would show up as B12 in the serum (once again this would show up in the active B12 test).
      So if the B12 that is being measured is “inactive B12” you would need to replace it with active B12. This presumably is what was happening when you were supplementing.
      Of the people whose levels that I know were high, most if not all appear to have improved with high dose mixed adenosyl/methyl VB12.

      • Thanks for this, Gregg,
        It’s great to have some idea of what to look for. I’ll take your comments to my doctor and find a way to get the active b12 test.
        Regards,
        Leilani

    • St. Thomas’s Hospital in London will do an active B12 but you have to pay for it. I investigated and if your GP writes a letter they will carry one out, but the onus is on you to pay.

    • I don’t know what my serum level was before I started taking the sublinguals, but it was 800 after. My doctor — who never heard of MMA — advised against taking more B12, which I ignored.

      Three months before (when I hadn’t taken B12 yet), I could barely walk into her office, where I complained about all the symptoms I had. After the B12, I practically ran up the stairs to her floor, and had no more complaints.

  6. My B-12 is high and my doctor has no idea if I should continue to take a multi? I have SIBO and IBS.

      • Greg, Thank you very much! I’m going to a new Gastro Dr in a couple of weeks and will be sure to discuss the bacterial overgrowth and my B12 levels and anything else the SIBO is interfering with. I’ve had trouble with my vitamin D levels also. If I could only get rid if this SIBO.
        Thanks again,
        Kristi

  7. Have an important question hoping you can answer as trying to figure out treatment for my daughter. What happens when you are allergic to cobalt/b12? I am at this point. do you think that there is a problem elsewhere in the cycle and the cobalt/b12 just builds up? If on skin it burns/scabs skin. tried testing at home with activated form, but test was inconclusive. when activated form given, skin gets worse. but i fear for anemia too and the effects as to not having it. She has had to stay away from anything that contains it-milk, cheese, fortified foods or grains, etc. not many people dr even deal with this in depth. maybe you can help. we do have her genetic profile too and where other mutations are.

    • Hi Cari, Although this is very rare, it does happen. From careful examination of the literature it is still not clear if it is an allergy to vitamin B12 itself or due to some minor contaminant in the preparation that the person is allergic to. As far as I can see, several people who have been allergic became allergic after having injections. Once they found they were allergic to say cyanocobalamin they switched to hydroxocobalamin. I have not found any references to anyone being allergic to adenosylcobalamin. I would definitely try to source a different brand or type of vitamin B12 and see if that helps. You can just do the little skin test with it.

  8. I have just been seen by an endocrinologist for the first time. He is running a b12 test on me amongst many,many others. I have had so many symptoms of B12 that I believe now that have been “misdiagnosed” all these years when 10 years ago when I was diagnosed with Bi polar and Fibromyalsia because of tingleing pain in my legs and feet that I cringed and procrastinated to put my feet on the floor in the morning. I could barely walk. It wasn’t until I was put on Lyrica that the pain subsided. I take just effexor now and it seems to be controlling the pain. And I was also taking metformin for several years, I have been on and off Iron pills and Vitamin D pills by my primary doctor. I also have all the symptoms of hypoglycimia but blood results of Hypergclycimia. I dont know if that fits in anywhere but I am to the point that I dont care what the news is, I need a definitive answer! Anyone have any ideas? Anyone else have a similar story? HELP!

  9. Hi Colleen, You’re better off getting potassium from bananas or other food than from supplements. Potatoes, tomatoes, and many other fruits and vegetables also have lots of potassium. If you take a supplement, potassium gluconate is easier on the stomach than potassium chloride. I use potassium gluconate because I don’t eat many fruits or vegetables.
    Don’t bother with the magnesium test. The usual tests are notoriously unreliable. (I have a reference to a study showing that RBC magnesium can go in the opposite direction of body load.) It’s best to do a trial with a magnesium supplement and see if you feel better. It’s very hard to overdose on magnesium. Some people do OK with the citrate form, but I find it’s an effective laxative. The amino acid chelated forms are probably best. I prefer the glycinate form. Many people like the malate form.

    • Mike the chemist today gave me Magnesium Forte. to take one a day (Magnesium oxide-heavy457mg,Magnesium citrate nonahydrate 870 mg etc)
      Unfortunately i need a script from my Doc to get potassium supplements.As im a vegetarian I do eat alot of fruits & vegetables so will stick to bananas etc for now.

  10. Hi to the group, just thought that I would update you on some information that I found with hypothyroidism and vitamin B12 deficiency. Several studies have now shown that up to 40% of people who have hypothyroidism either have anemia or are vitamin B12 deficient. Now that does not include all the people who are sub-clinically deficient in vitamin B12. So what is the link. Well it is a bit complicated and there is quite a detailed description on the http://www.vitaminb12deficiency.net.au web-site. To the short answer is that thyroxin produced in the thyroid, is involved in the conversion of riboflavin (vitamin B2) to FAD. Now FAD, plus vitamin B3 is a co-enzyme for MTHFR, so if you can’t make FAD, then the MTHFR won’t work. You then can have simlar symptoms and deficiency to those with the mutations in the MTHFR gene. One of the reasons that this is hard to diagnose is that hypothyroidism has some similar symptoms to vitamin B12 deficiency. This also has applicability for those with mutations in the MTHFR gene, who should make sure that they are fully “primed” with B2 and B3.

    • Greg,

      You mention that those with mutations in the MTHFR gene should make sure they are fully “primed” with B2 and B3. Does it make any difference if the B3 is nicotinic acid, niacinamide, or NADH?

      Also, niacin is known to deplete methyl groups. Does this depletion happen only with the nicotinic acid form of B3, or also with niacinamide?

      • Hi Lynn, you definitely need vitamin B3 to make NADH, which is an essential element of the Krebb’s cycle as an electron acceptor and then in the electron transport chain to donate electrons. This is apart from its role in MTHFR. If you are deficient in it, not only will you have problems in making 5MTHF, but your energy systems will definitly “go slow”. No need to go beserk with supplementation though. You can make it from Tryptophan. You can check out the RDA at the Linus Pauling web-site http://lpi.oregonstate.edu/infocenter/vitamins/niacin/ . As for the methyl group depletion, I don’t know if I am a strong advocate of that theory. It is involved in the conversion of methenyl-THF to methylTHF (5MTHF), so technically it is a methyl generator. It has been used at high doses for lipid depletion and atherosclerosis control. Possibly this is due to its role in the CAC. I would, however use nicotinamide, rather than niacin or nicotinic acid, which are supposed to cause flushing.

    • Hi Greg,this just seems to be getting more complicated for me.i had my first lot of B12 injections back in june.my DR gives daily injections i understand other doctors give weekly injections until levels are high enough than 3 monthly for life.i have fely very light headed & extremely tired .im just getting through the days doing the necessary stuff.this is difficult having a 6,8 and 16 year old who are energetiic.ive had tests recently Intrinsic Factor Antibody (negative )Antiparietal Cell Antibody (negative).my serum B12 is 1476 pmol/L.. when i was first tested for B12 my levels were 175 pmol/L .my thyroid meds have been reduced to 100mg a day as i have hypothyroid.now im confused if i had thyroid problems first or B12 deficiency.even though i have been treated for my hypothyroidism for 16 years ,think alot of B12 deficiency symptoms happening back than also.The b12 injections are hydroxocobalamin.i have also purchased the Transdermiol to try when my levels have dropped.think i will get levels tested first & try the oil for abit & get tested again to see results..my Dr doesnt seem to explain alot or want to discuss options ,necessary testing etc.wondering if high levels can make you feel lousy and can it take sometime after treatment to feel normal.just want to work out why im deficient & what tests to have that may help improve things .

      • @Colleen – The light-headedness and fatigue can be symptoms of potassium deficiency. You were badly deficient in B12, and that slowed some healing/growth processes in the body. When you replenish your B12 reserve, those processes speed up; which can use up your potassium reserves. Another symptom of potassium deficiency is twitching or cramping muscles. I developed a few facial twitches and leg cramps after I started taking B12. Supplementing potassium and magnesium was very helpful. Potassium and magnesium work together, so it’s a good idea to supplement them together.

      • Hi Colleen,
        The chicken and egg story with thyroid and vitamin B12 deficiency. My reading of the chemistry is that the hypothyroidism can theoretically cause the VB12 deficiency, and many people who have been shown to have hypothyroidism are VB12 deficient, supporting that hypothesis. If you were not tested for your VB12 levels early on you won’t know when you became deficient. As for not getting your energy levels up with hydroxocobalamin, my guess would be that either you are not converting it efficiently to adenosylcobalamin, or you have a deficiency in one or more of the othe B group vitamins involved in the citric acid cycle, such as B1, B2, B3 and B5, or zinc (essential for the electron transport chain, ETC). There are genetic conditions where people cannot make AdoCbl and need to be given it, particularly if they are not getting it in their diet. Normal supplements have CN-Cbl at worst or OHCbl at best, so the best source is the diet (red meat). Another important thing for conversion of OHCbl to AdoCbl is intracellular glutathione (GSH). Evidence suggests that the level of GSH inside cells may be reduced if someone is taking too many anti-oxidants. Also if have low levels of sulfur (methionine or Cys) in your diet you can have troubles make GSH, and troubles making some of the ETC proteins. Wait and see how you go with TransdermOil product, if you still lack energy, then it may be the B group vitamins.

        • Thanks Greg Im getting desperate to find an answer as im struggling to get through the days and its affecting my kids.My husband doesnt complain but its not fair when he comes home on his days off he practically does everything & I keep going back to bed.
          I try to make sense of what im reading but my brain still isnt functioning how it should & its hard to take it all in & understand it.Im wondering if i should start on the oil now or wait til my B12 levels drop abit from 1476pmol/L .im wondering the oil is going to send my levels up extremely high if im using it once a day.

          • Hi Colleen,
            It sounds like there may be a few things to consider here.
            This might be a better chat “off-line”. Can you email me at
            [email protected] and we can go through the scenarios a bit further?

  11. I am 41 years old and went to the doctor because my feet and hands were having problems, anyway they diagnois it and said i was b12 low (my test results was 50 and supposed to be in the 300). Anyway they prescribed b12 vitamins one a day.

    Does anyone else feel very warm and sometimes hot from taking the b12 vitamins? I am alway warm, when i sleep i am sweating that much that the blankets are damp?

    • Hi Karen,
      Probably not all that surprising. If your levels of vitamin B12 were so low, your metabolic rate (which is the rate that you burn energy) was probably very low, and so you were not generating a lot of heat yourself. Now you are having vitamin B12, your mitochondria (the little power-houses in the cell) are able to function faster and they generate the heat. You have probably got used to being colder and so now you feel hotter as your metabolic rate is higher. It is a good sign, it means that the VB12 is working.

    • Karen – my levels are awfully low, much like yours – was wondering how you are feeling now and have you had a follow up check on your B12 levels? If you could let me know on how you brought your levels up that would be great. Hope you get to feeling better!

  12. hiya, ive been told today that my b12 test has came back low at 168. ive goto have 6 injections in two weeks and one every three months after that. ive got a lot of neurological problems and have recently been put on 150 mg of b2 for glutaric aciduria type 2. ive also been on 5mg of b9 for past 5 or so years. is it just a coincidence that im on 3 different b vitamins or is it all related. i havent got a clue. thanks

    • Oh, that sounds bad, you must be worried. You may have to educate your doctor a bit. All of us have had to do it. Try to find out what type of vitamin B12 he/she is going to inject. If you can get hydroxocobalamin good, but cyanocobalamin is not what you want. Do you know why you are deficient. Is it whatyou eat,or is it some of the genetic problems that so many people on the site have?
      You will work out that you need to know. Do you know if you are deficient in anything else?

  13. Recently a doctor I have been seeing has recommended I supplement with B12, I am sure based on an elevated MCV of 101. I have been taking a supplement (2 per day) for at least 18-24 months that includes 50mg B6, 5mg Folic Acid, 1000mcg B12 (methylcobalamine) and Betaine HCL 500mg. I have also exhibited B12 deficiency symptoms, ie. fatigue, memory issues, lack of motivation, numb fingers (recently). The doctor making this recommendation is addressing hormonal issues of note, as I am hypothyroid and my hormones are out of balance so I am taking bioidentical progesterone, estrogen, cortisol and thyroid to address these issues. I am not close to the optimal dose for my thyroid yet which I thought was the main issue causing fatigue. Anyway, I am wondering if I am not absorbing the B12 that i have taken for the past year and a half. I recently started taking a sublingual B12 supplement that is cyanocobalamin to see if I have positive results. Otherwise, I would like to try the methylcobalamine, (have found Jarrow 5mg) but after reading this blog, I am concerned about supplements that should be taken with this form of B12. Are Folic Acid and B6 the supplements that I should take along with this form of B12? If I take the methylcobalamine sublingual, would it be sufficient to take the Folic Acid and B6 orally as long as I take them concurrently? I would appreciate your comment on this.

    I love your website! It is refreshing to find medical information that makes sense. I feel affirmed in my own conclusions after looking at the evidence of my own issues. Keep up the good work!

    • Hi Rachel,
      Welcome to the group. Interesting problem you have with the hypothyroidism. Looking into the biochemistry thyroxin (made in the thyroid) actually has an effect on conversion of riboflavin (B2) to FAD. When you are low in thyroxin you can’t properly process B2 to make FAD. Now FAD is an essential co-factor in the MTHFR enzyme, which you will read much of on this site. This then means that you can’t properly process 5;10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. This in turn means that you have problems processing methylcobalamin (MeCbl) and so it goes on. If you cruise around on http://www.vitaminb12deficiency.net.au and look for the section of MTHFR mutations you will get to the page on the chemistry of it. Sort of helps you to undestand the problem, although not sure if it useful if you don’t have a chemical bent. Oral high dose methylCbl supplements are not great and you will see some discussion on the web-site. Also from the discussions you may see that it looks like you may have to supplement with adenosylCbl as well (it is involved in energy production in the mitochondria).
      CN-Cbl definitely is not the best form to take, it is a provitamin and if you smoke or live in a very polluted city it is even worse. Minimun would be OHCbl, with best the mix of Ado and MeCbl.
      As for the supplements, it is likely that once you are deficient it has a very negative effect on cell division and maturation, and those who are deficient also have trouble with absorption of the other water soluble vitamins. You definitely need the lot though B1, B2, B3, B5, B6 and B12 (Ado and MeCbl).

    • Hi Rachael

      I also have hypothyroidism and have been B12 deficiency. I have found great success using Freddd’s Active B12 protocol for about 15 months. After 6 months I found I could convert T4 to T3 and handle an adequate amount of natural dessicated thyroid hormone to relieve my hypo symptoms. Being hypo and B12 deficient was a real drain on my adrenals! In my opinion, you need to address both the inadequate thyroid hormone and inadequate B12/folate before you will feel well.

      I use sublingual methylcobalamin (I like Enzymatic Therapy b12 infusion) and adenosycobalamin (marketed as dibencozide). I keep the B12 in my mouth for 1-2 hours and that way it absorbs well. I also take folate in the form of methylfolate. All of these are available online without a prescription. I avoid folic acid which is not well converted or absorbed, and may block real folate from reaching the cells. I also take a vitamin B combo that contains no folic acid. Pure Encapsulations makes a B combo with extra B6, and no folic acid.

  14. Hi Greg,

    Hcy and MMA all return to normal after treatment commences and usually within 10 days. ‘Treatment’ can be as little as 3mcg. I’ve got a study somewhere. Murphy and Minot also reported that all haematological symptoms return to normal after 10 days. A US study also reports that ‘once treatment commences all haematological indicators return to normal.’

    What we’ve got to remember here are that haematological indicators are symptoms indicating a deficiency – that are not a diagnosis. The same goes for the haematological indicators in M&Ms day – except then they were looking at RBCs and reticulocytes.

    All it means is that once treatment commences ALL blood tests should revert to normal because those particular symptoms have been remedied. Then you’re just left with the rest.

    I don’t know who ‘We’ are. But I think if you are doing any form of research, with a condition is potentially lethal, then you should at least realise the significance of blood test results being resolved very, very, easily.

    The people who are reading this page, for the most part, may not realise it but they are very, very, lucky, because they are the ones that have at least had the deficiency identified before they got to the stage that they couldn’t resource information for themselves. But, if they don’t do it right, it can all go wrong very, very quickly.

    What I think should be remembered by all is that there is no standard treatment. Murphy and Minot got it right: “Maintenance dosage varies with the needs of each patient.”
    Until we know more, then that’s what we all have to do.

    • I have no idea what improvements you are seeing with topical applications and how these are measured and against what control groups – I’ve never heard of any scientific studies being carried out, I’ve never heard it suggested. If there is a product however, I’m sure it must be licensed in some way, shape or form.
      But if you consider that most treatments for b12, if they are given correctly, produce some form of improvement we have to draw the conclusion that b12 deficient patients improve if given the correct treatment. No surprise there then. M&M proved that in the 1920s.We’ve not come very far, have we?
      And you should never use the word ‘cured’ you can only get improvements with on-going treatment. We are, at this stage in history, not able to be cured. In the same way you cannot ‘cure’ a diabetic.

      • I also don’t know if you are aware that there is a product, with the initial V (and it’s not Vichy) that have been making a b12 creme for both face and body for several years now. Small amounts of cyanocobalamin admittedly, but this is supposed to stop wrinkles – again no official research.With the amount of stuff I’ve smeared on me in the last 3 years, according to your logic, I should be absolutely fine with no further supplementation. I don’t think so.

        • Hi Kaytee, there is a very famous quote in the formulation world. “Oils aint oils”. Oils are also not creams.
          If you know about formulation a cream is a cream, it is not an oil. They have very different properties as far as what the bulk phase is, the percentage of water, surfactants, waxes, oils, etc.
          They also have massively different properties as far as skin penetration goes. So I am totally not surprised that your water-based, non-transparent, wax formulation (cream) does not penetrate the skin. This it a totally different formulation to an oil based completely transparent formulation that is the basis of the transdermoil formulation.
          So according to my logic, your Stuff that you have smeared on you for 3 years, absolutely wouldn’t work. However, that is probably not what all the manufacturers of skin moisturizers, skin rejuvenators, and those that now promise DNA repair to the skin would say. On the other hand we have much data that says that the transdermoil formulation does work.

  15. I think whatever studies we are referencing then we are in agreement that more, in this case, may not be better. There are several referenced studies relating to smaller more oft dosages being more effective than the larger, less frequent amounts. This would be confirm by the scientific basis of how b12 is loaded, and it would also be confirmed by the revered pioneers of the treatment for this illness who recommended that patients were dosed, on average, every two weeks, and also that needs varied with each patient. I am, of course, talking about Murphy and Minot.

    However, none of the studies prove how effective the treatments are at cellular level. Not that I’ve found anyway. And, we are back to the same old, same old, that such indicators are not available to us and therefore we must treat according to how symptoms are relieved.

    When it comes to topical applications. Nice thought. Very simple. But I still can’t see how this would work effectively, as the product currently stands, via this methodology. A patch is different, it is on most of the time, testosterone is different. There are approximately 14 different proteins involved in transporting b12 – it is one of the most complex substances the body utilizes. Has the question been asked if the stores in the liver are analogues – if they haven’t had the correct transportation procedure are they just being stored and not available for utilization? We know that b12 deficient patients carry a lot of b12 in the bowel after it has been through the system but we also know it cannot have been utilized.

    Like I said, there are many people out there whose lives depend on b12 – and I might add, most of them have never been recognised as being b12 deficient. They die of unknown causes. Would we really think a topical application would be sufficient to save their lives without being absolutely certain of how this worked and if it worked effectively at cellular level?

    After being involved with this subject for several years now and sitting looking at thigh muscles that don’t bother flexing anymore, I am very aware at how this condition can be trivialised by all concerned. I’m including scientists in this because they have never really seen the end results. They really don’t know what happens to people when you take them to the wire. Because most people die of a heart attack, a stroke, cancer or dementia before their bodies deteriorate to the point of extreme emaciation and death.

    Personally I wouldn’t be promoting any product until you were absolutely 100% sure of if it worked and how it worked.

    This is very very serious stuff.

    • I think I should also mention, that no matter what the stores in the liver, it is indicated in malabsorption patients that the enterohepatic system does not function correctly, therefore these stores are not being taken up and recycled properly. Again, another problem which points to us needing a test that effectively establishes whether the b12 is restoring/regenerating/repairing tissues.

    • Hi Kaytee,
      I agree with many of your points.
      There are however studies showing that at least in some studies you do get material to the cells and alter the metabolism. These studies have looked at changes in MMA and Hcy, and have shown an effect.
      We are currently in the final stages of comparing all the types of supplements in those that are deficient. It is taking a long time to organize as one would expect.
      As for knowing whether the topical material works before the study, I would say this. We have patients who have had the typical VB12 deficiency muscle tremors that we have managed to “cure”. We have patients with FSHD who have managed to get improvement in muscle strength. We have also caused weight loss in patients, presumably by increasing mitochondrial output. We also have had several people reporting increased energy levels. We are pretty convinced that it works.
      I agree about all the problems with the non-diagnosis and even non-treatment of those who are deficient. I personally am appalled at this, having my mother, who was highly intelligent reduced to almost incoherency through the use of metformin and the lack of knowledge of subsequent VB12 deficiency.
      There is much to be done in the area, but you have to start somewhere.

    • Hi Kaytee,
      I agree with many of your points, particularly about people not being diagnosed with deficiency and dying without ever being tested.
      I also think that any replenishment of the system and repair of damage caused by deficiency is going to take a long time, particularly if it involves remodelling of myelin, replacement of MBP, etc. I don’t think that most people realize this, they seem to think that if you get serum levels of VB12 (of unknown type) that that is sufficient. You just have to look at the approach to VB12 injections, where they basically wait until the patient is deficient again before they re-inject. In the meantime the patient has been in partial insufficiency for most of the time. Our calculations suggest that upwards of 20% of the population in the US and Australia is deficient and possibly has signs of sub-clinical deficiency. This is without throwing in the calculation for the 16% or so who are homozygous for MTHFR mutations.
      It is for this reason that the transdermal application has so much promise. It slowly releases saturating amounts of VB12 over hours and hours, thereby hopefully allowing for full saturation of TCII and uptake into the cells and transport into the CSF. It is also the reason for including both Ado and MeCbl in the formulation so that you give the cells every chance to operate properly.
      Yes it is very serious stuff and much more so than the majority of the medical profession will give credit. You just have to go to the majority of the relevant web-sites that totally avoid the problem or suggesting the solution.

      • I think you will find that on the rare occasions MMA levels are tested prior to treatment (in any form) the figures suggest that in certain demographics the percentage is a possible 44% of people suffering from sub-optimal b12.
        My concern here is that there is no evidence that topical applications work at all and the ‘science’ behind it is flimsy at best and should not be recommended to patients with a potentially lethal illness. In fact, this is an illness that has always, prior to treatments being available, as a ‘distinct morbid entity.’ You will die if you don’t get the correct treatment.
        And the problem has always been that – patients struggling to get the ‘correct’ treatment. And most patients struggle to get the correct treatment and therefore will try anything.
        But ‘anything’ doesn’t work either – it still has to be proven – because the risk to the patient is permanent physical injury or possibly death.
        That’s why I say, you have to be 100% certain of what you are claiming, because lives depend on it.

        • If I was deficient, this is what I would take, there is nothing that I have seen that would be better.
          Why not try it before you defy it?

        • I do not believe there is a 100% remedy for this, what works for some may not for others. Fact of life.
          Definitely worth trying.

          • I agree, although I have tried the product that I believe Greg is talking about and it seems to work for me. I have had PA for over 20 years, and have been thoroughly fed up with injections, so it was really nice to try something different and find it works.

  16. I know that there were studies done on passive diffusion reporting the 1% uptake but have never seen them although the figure is well reported.
    The injectible absorption rate studies which I’ve seen, ‘roughly’ because I’m not looking at them, said 100% at 3mcg and 15% at 1,000mcg. I still don’t know just how they established this though.
    With the oil I’m certainly confused at how it would be picking up the transport protein in the digestive tract. Using the logic the sales people seem to be using simply means that we could all put some b12 in a carrier oil and rub it on.
    Since, like many others, my life depends on getting enough b12, I wouldn’t like to chance that this does pick up protein carriers in some way without substantial evidence.

    • Hi Kaytee,
      The 1% is an upper limit on uptake, with particulates it is more like 0.1%. If you use mucoadhesives, thre are some reports of 1%. Bit of a pharmaceutical science question though. I have never seen 15% at 1000 ug, data I have seen is 90% of 1 ug dose, 45% of 5 ug dose, and <10% of 100 ug dose. You can repeat dosing very hour or so, but you need to restimulate the parietal cells to secrete HCl and stored IF. People on antacids absorb much, much less due to inhibition of HCl and IF secretion.
      If you look at oral biodistribution studies, you only measture 5% of the absorbed dose go to the liver, the rest is pretty much the same % per gram. Normally with VB12 you have to decide whether to include the material that is in the gut (small intestine, stomach LI) as having been transported, in the process of transport, or travelled back to the intestine, so it is confusing.
      With injectable dosing, you get a very similar biodistribution, with around 5% of the retained dose going to the liver. As soon as you over-dose all the "over-dose" goes into the urine.This is also what people report who have hydroxocobalamin who complain that they get purple urine (OHCbl is a purple/red colour, not red or pink). This is the reason why injectable doses don't really load up the liver. If you assume that you actually "loose" 5 ug/day of VB12, and injectable doses last 28 days, you can work out that for an injectable dose of 1 mg dose you only retain around 14%, so the rest is lost. Studies in most animals are very similar, the main difference is the absolute amount that is taken up by the IF-mediated uptake system. From memory some of the studies are reported in the book "Comprehensive B12" by Scneider and Stroinsky. Don't currently have the book though.
      As for the "oil" it is not taken orally, it is specially formulated in quite a unique formulation (no not just any oil – I've tried), which is applied topically, and then goes into the skin transdermally. It then persists for hours in the skin, slowly diffusing out and becoming available. It has the advantage in that it can slowly load up the TCII carrier system. I don't know if you are in the area, but if you know the pharmacokinetics, it is similar to testosterone in patches or in topical oils.
      My apologies to those who don't like the technical questions, but in this instance perhaps you will be patient with us.

  17. Hi,
    Gregg – Can I ask for links to the studies that show the uptake of b12 via injection/oral/oil treatments, please?
    Also can I ask just how the uptake percentages were measured ie though tissue sampling etc?
    Thanks.

    • Hi Kaytee, the studies that I refer to have been studies using 57CoVB12, which used to be readily available. They were dosing studies done in mice where all tissue samples were measured. Tissues are dissected out and put in a gamma counter that measures the 57CoVB12. That way you can accurately assess exactly how much gets in. You can also see what happens to it over time.
      Unfortunately the studies weren’t published as we didn’t think that is was that important at the time.
      The comments on the doses available orally in humans are well known, but you will have to go back many years to find them. 57CoVB12 is not used now.
      Studies on transdermal deliver have been done with quite a few molecules, but as yet unpublished. They have shown good uptake through the skin with water soluble molecules, even, proteins as big as 150,000 MW.
      If you are interested I can send you pre-print material, but as it isn’t published as yet I can’t put it on line.
      The important thing in all of this is that one must understand that just as there is a transporter (intrinsic factor) to get VB12 into the body orally, there is also one (transcoblamin II) to get VB12 into all tissues. If the VB12 is not on the transporter it doesn’t get into the cells where you need it.
      Limited uptake of vitamin B12 orally is very well known, however, there seems to be comments suggesting that it magically gets across the intact cell membrane if you throw high enough doses at it. One way of thinking about it is by thinking of cars and a ferry. The ferry will only take so many cars across the water at a time. It doesn’t matter if you have 2 or 1 million cars waiting, it only takes the same number across. High dose oral is a very similar situation. Lots of VB12 but only a limited number of ferries. If you want to test it yourself, take some of the high dose VB12 (methyl or adenosyl or CN, or OHCbl. Dissolve it in water and then see if you can get it into vegetable oil. IT WON’T go in. The cell membrane in the gut that you are trying to get across is like the oil. Even water itself won’t penetrate the cell memebrane unless there is a pore – look up aquaporins if you are interested..

  18. Hello Chris, I follow a FODMAPS diet and see that b12 sublinguals always have some kind of sugar alcohol (e.g. sorbitol) that really aggravate my gut.

    Any suggestion on how to supplement with b12 for those of us who have gut issues (which, not coincidentally, are why I need b12 in the first place)? Should I open my methylcobalamin capsule and try to let the powder dissolve under my tongue?

    • Hi Patricia,
      We appreciate this problem. There are two issues here, firstly the mode of delivery and secondly the problem with your gut issues.
      The amount of material actually absorbed from sub-linguals and high dose oral is at maximum 1%, even in an intact gut. Given that you have intestinal issues it will be less.
      There is a transdermal delivery system that has recently been developed with a product that delivers both Adenosyl and methylcobalamin. Data suggests that AdoCbl is subverted to trying to make MeCbl, so you become deficient in both, hence the dual delivery.
      The product is available from http://transdermoil.com/products/transdermoil-b12

      • Greg, are you saying that the B12 Infusion (methyl cobalamin) a lot of us have been taking is not really any good? I am curious about the product you posted, and how it is more absorbable by the body. Thank you.

        • Hi Julee,
          You raise some interesting points that I will try to address.
          Firstly the high dose oral/sublinqual tablets, gels, lozenges and sprays. All of these work on a similar type of principle, and that is that if you take enough material you will get a little bit of the material in. The “little” bit is pretty much proportional to the amount that you deliver and is about 1% of the dose. So for a 1 mg dose you get around 10 ug across the gut wall. Now this is marginally better than the normal intrnsic factor-mediated (IF) uptake, which is studies in humans have show can be up to 90% of 1 ug dose, and 45% of 5-10 ug dose. Dosing studies have shown that basically this is the amount that you can get in via the specific uptake mechanism. In order to increase the amount you have to greatly increase the dose administered, hence the high dose formulations.
          The second question is the type of VB12 delivered. In the body you use methylcobalamin as part of the methylation cycle, which can be “upset” or perturbed in those with the MTHFR mutations (a topic also discussed on this forum). This is a hugely important cycle and data now suggests that if you don’t methylate properly you can get increased incidence of MS, RA, dementia, etc.
          The other form of VB12 you use in the body is adenosylcobalamin (co-enzyme B12). This is used in the mitochondria for energy production. If you take high dose methylCbl, and you don’t take adenosylcobalamin, you can still feel like you lack in energy. So really you need both.
          Now getting onto the transdermal oil. This contains both forms, methyl and adenolsylcobalamin. Uptake through the skin in similar to how a “vanishing cream” vanishes. Little tiny drops of water contain the adenosyl and methylcobalamin within a special oil that you rub into the skin. If you enquire of the company they can arrange for you to have either separately or together. I am happy to talk about this “off-line” if you want. I also have further information on the web-site http://www.vitaminb12deficiency.net.au , which I update as I get further information.
          Oh the other thing is, once you are deficient enough to notice, you probably have lost 3-4 mg of stores of VB12. If you only replace this at 5-10 ug /day you can see that it will take a long, long time to get your levels normal.

          • First, thank you so much for replying! I have asked several questions on here before, and have only ever gotten one response. I asked about the product you mention because after taking the B12 I mentioned for over a year, I had company this last week and because of a crazy schedule, I have not taken it this past week … And I feel better, more energized. I just wonder if it is doing anything for me. I am due to go to the doctor and get all of my blood work done, so we shall see if my numbers are any different.

            • hi Julee,
              Thanks for the thanks, a pleasure.
              I don’t know your whole history so it is hard for me to judge from here.
              What I can tell you is that the long term consequences for VB12 deficiency below 300 pmol/L are not good, and include nearly all the symptoms that you read about on this site. Other conditions such as eyesight, hearing, incontinence, RA, MS, dementia and Alzheimer’s are even more worrying. Whilst I don’t have any of these problems, I still take the topical B12, on a just in case basis. I can tell you though that I believe that my memory is improving, and that my hearing seems to be more accute.
              So, if you can find a source of VB12 that doesn’t give you the side effects of your product then I for one would be on it.

  19. I’m a 19 year old girl, and I was diagnosed with B12 deficiency about a month ago. I have since recently started B12 injections and a strong dose of folic acid. I was constantly tired and I had these sort of niggly pains in my feet and hands. I’d also get like shocks or zaps randomly in parts of my body. It’s still happening quite a bit, but I’ve only had 2 injections so far. I’m getting my next one this week. I’m just wondering does anyone else suffer with these symptoms?

    It’s very annoying and often keeps me awake. I find myself very twitchy and irritable also. Like if someone touches off me I’ll jump. I’m quite cranky and hard to be around. The smallest things will set me off. It’s affecting my relationship with my boyfriend also. He’s very patient and understanding, but often I find I take my frustration out on him, which isn’t fair I know, and then I feel horrible afterwards. I’ll get very teary too.

    Has anyone had any similar experiences? Does it get better? I’m hoping the more injections I get the more I’ll feel like my old self, because I’m quite down at the moment. I feel like I’m angry all the time!

    • @Jessie – Those are all symptoms of B12 deficiency, and they should improve with supplementation. Google for “peripheral neuropathy B12”. If you can find the book “Could it Be B12?” (second edition) at a library or bookstore, read chapters 3 and 4 to better understand what’s happening to you.

      If the shots don’t provide improvement*, try sub-lingual B12 tablets. I take Enzymatic Therapy B12 Infusion, Country Life Dibencozide (another form of B12), and Solgar Metafolin daily (folate is essential for the use of B12). The B12 and Dibencozide tablets should be held under the tongue or between lip and gum for at least 30 minutes, or an hour if you can manage it. I usually feel a bit spacey for an hour after taking them, so I take them when I’m not doing anything challenging.

      *One reason the shots may not help is that they often include inactive forms of B12 – cyanocobalamin or hydroxocobalamin. Some people have trouble converting them to active forms. It’s better to get the active forms – methylcobalamin and/or adenosylcobalamin/dibencozide. Try to talk your doctor into prescribing methylcobalamin shots if you’re getting something else. The book “Could it Be B12?” has good info to help convince your doctor to make the change.

      • Hi Jessie, Mike is right about the symptoms.
        What your doctor may not have told you is that once you have peripheral neuropathy or other nerve damage it may take quite a while before the symptoms go away. If you have been sub-clinically deficient for long enough you actually start making faulty myelin and faulty myelin basic protein. Now the body only turns these over very slowly, so you have to wait until the faulty material is replaced before all of your symptoms disappear.
        Also you need to check what shots you are getting. Cyanocobalamin is the worst, followed by hydroxycobalamin. The best thing would be the mixed methyl and adenosylcobalamin. You can get the mix from http://transdermoil.com.
        If you are really deficient you need much more than you can obtain from sub-linquals or high dose oral tablets.
        One thing that is not discussed in the forum is that you actually need to get your VB12 onto the specific transporter for vitamin B12, transcobalamin II. If it is not on this transporter the vitamin B12 will not get into the cells or the brain, but it will be wasted. So it may look like your serum levels of vitamin B12 have improved but if it is not on transcobalamin II you might as well not have it. Sub-linguals and high dose oral does not effectively load up the transporter, although is does give a temporary boost in serum VB12 levels. This is born out by several comparative studies on efficacy.

      • @Mike S. @Greg Thank you both for your informative advice. I’m getting my next injection tomorrow, So I will speak to my doctor about all of what you mentioned then.

        I also have another inquiry. Initially when my symptoms began, I was away at university so I visited the doctor down there. She did sensory tests etc, and ordered blood tests as she suspected it could be an issue with B12. I was told to make an appointment in a week to check back for results. Long story short I never got the results. I had horrible trouble getting them back due to an incompetent receptionist. She kept telling me she would get someone to call me with results, which never happened, she also told me they couldn’t give the results to my own GP back home, unless he requested for them in writing.

        Anyway after that I went away for a month at the start of the summer and symptoms persisted. When I returned I went straight to my GP at home, explained the previous situation and asked for more blood tests and a B12 check. Low and behold I was badly deficient. Now, what I’m wondering is had I left it longer, lets say I didn’t bother getting more bloods done after not getting the first set back, would everything have gotten worse? I’m just really angry at my University’s health center and the treatment I received.

        Is it serious enough to actually pursue action over? Just looking for opinions. Thank you again. Everyone here is so helpful.

        • Hi Jessie, we do helpful, but probably not legal.
          The main thing it that you now know that you are VB12 deficient, presumably through your diet.
          The most important thing is to get your levels up and get them to stay up. You would almost certainly have got worse. So now you should aim to get way above 300 pmol/L and keep it up. Being low you will probably have done considerable sub-clinical damage to your nerves (particularly in the brain) and you have to get your levels up to repair this damage. Next thing is to spread the word and help educate those around you. Hopefully then the medical profession will listen. Our calculation suggests that up to 20% of the population is sub-clinically deficient. That is without the contribution of the MTHFR population. Despite this people are still taking ant-acids, products for GORD, metformin and similar drugs. B12 levels are not routinely checke in women before, during and after pregnancy, despite the evidence that VB12 deficiency is as bad for the fetus as folate deficiency.