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Vitamin B12--Sublingual, Nasal Spray or Oral? . . .Should You Swallow?

Vitamin B12--Sublingual, Nasal Spray or Oral?

Should You Swallow?

“So, you are saying that the Sublingual B12 does not work as a sublingual because the molocules are too large to be absorbed through the barrier. Does the nasal spray version work ?”

This comment was posted on my blog,, in response to a post titled “Vitamin B12: Sublingual Form?” originally dated October 11, 2010.

The current question about nasal spray vitamin B12 is a valid one.

First, let’s look at why this discussion persists. Vitamin B12 is an essential vitamin, “playing a role in DNA synthesis, red blood cell formation, homocysteine metabolism, and synthesis of S-adenosylmethionine. It is involved in the functioning of the nervous system and immune system.” The problem is that due to its unique absorption mechanism, correcting deficiencies is not always easy.

Before I explain why this is so, let’s look at a slightly more technical explanation by Dr. Alan Gaby (Nutritional Medicine. Alan R. Gaby, M.D., 01/2011.) :

“Vitamin B12 in food is usually bound to protein. It is released from the protein by the combined action of gastric hydrochloric acid and pepsin, and then binds to intrinsic factor, which is secreted by the stomach. The vitamin B12-intrinsic factor complex is absorbed into the bloodstream in the ileum. Crystalline vitamin B12 used in nutritional supplements does not require the action of hydrochloric acid and pepsin in order to be available for binding to intrinsic factor. Some 50–75% of vitamin B12 bound to intrinsic factor is absorbed, but intrinsic factor becomes saturated at vitamin B12 doses greater than about 2 μg. Larger doses of vitamin B12 can be absorbed by passive diffusion, a process that is independent of intrinsic factor. While fractional vitamin B12 absorption by this mechanism is only about 1–2%, oral administration of high doses of vitamin B12 (such as 1,000 μg/day) can compensate for the loss of intrinsic factor (as in pernicious anemia). Pernicious anemia is a condition in which vitamin B12 malabsorption occurs secondary to autoimmune destruction of the gastric parietal cells (the cells that produce intrinsic factor.) . . . Hypochlorhydric individuals have an impaired capacity to absorb protein-bound vitamin B12 from food, but they absorb crystalline vitamin B12 normally. People with hypochlorhydria are therefore at risk of developing vitamin B12 deficiency unless they take a vitamin B12 supplement.”

Note that Dr. Gaby points out that large doses of vitamin B12, taken orally, can be absorbed by “passive diffusion.” In other words, enough B12 can be absorbed (about 1 to 2 percent) even in the absence of intrinsic factor, from oral dosage.

Let’s look at that from a practical standpoint. Supplements are available that provide 1,000 mcg and 5,000 mcg per dose. The form of vitamin B12 used in these supplements is methyl cobalamin, which is one of the coenzyme forms of vitamin B12. If 2% of the methyl cobalamin is absorbed, by passive diffusion, that will deliver 20 micrograms of B12 from the 1,000 mcg product, and 100 mcg of B12 from the 5,000 mcg products. At the time I am writing this, the 1,000 mcg product (Jarrow Formulas, Willner Code 34453, 100 Lozenges at $8.37) would cost you a little over eight cents per dose. The 5,000 mcg product (Jarrow Formulas, Willner Code 34918, 60 Lozenges at $20.97) would cost about thirty-five cents a dose.

That’s pretty inexpensive, isn’t it? And that’s why, when we say you get the same benefit from a “large” oral dose of vitamin B12, it is important to recognize that a “large” oral dose of vitamin B12 is very small when it comes to cost. Compare this to the cost of an intramuscular injection or of a prescription nasal spray.

OK, so what about “nasal sprays” as an alternative to oral forms or injections?

First, to the best of my knowledge, nasal gels and nasal sprays are not classified as “nutritional supplements” or “foods.” The FDA prohibited vitamin B12 nasal gels from being sold as over the counter nutritional supplements many years ago, and I assume the same regulatory status applies to B12 nasal sprays. They are available on prescription, however.

Do they work–whether on prescription or otherwise? The answer seems to be, “kind of!” I looked at the “package insert” for one prescription B12 nasal spray product, and I found the evidence a little vague. I am appending the pertinent section at the end of this article. You can decide for yourself.

At best, the same practical question begs to be answered, i.e. why spend all that money for an expensive, prescription B12 nasal spray when you can get the same result from an inexpensive vitamin B12 1,000 mcg or 5,000 mcg supplement?

And finally, here is what Dr. Alan Gaby has to say about B12 nasal sprays: “Hydroxocobalamin administered by the intranasal route has been found to be well absorbed.  Hydroxocobalamin given intranasally produced higher peak plasma vitamin B12 concentrations than those achieved with oral administration, but lower concentrations than those obtained with intramuscular injections. However, the long term safety of intranasal vitamin B12 has not been demonstrated, and it is possible that it could damage the nasal mucosa. Administration of cyanocobalamin by inhalation resulted in a rapid increase in serum vitamin B12 levels, indicating that the vitamin was absorbed through pulmonary alveoli. However, pulmonary damage could result from this route of administration, since pulmonary fibrosis has occurred in dogs exposed to prolonged inhalation of cobalt. Because of the lack of long term safety data, I have avoided the use of these forms of vitamin B12. Vitamin B12 for sublingual administration is also commercially available, but it is not absorbed more efficiently than oral vitamin B12.”  (Gaby, Alan R., MD. Nutritional Medicine. 2011. Available from Willner Chemists, Product Code: 59437, List: $295.00, Discount: $266.50)
In summary, there may be medical conditions requiring vitamin B12 dosing obtainable only through injectable or prescription medication modes. But, by definition, that is a medical application, and should be determined by a medical professional. What is important is that they recognize that oral dosage forms of vitamin B12 are no longer considered ineffective.

Don Goldberg

Addendum #1: Excerpt from original blog entry, Oct 11, 2010,
Dear Sir
I have been advised to purchase Jarrow sublingual methyl B12 (1000m)
My questions are:
1) Is a lozenge classed as sublingual? I understand that a lozenge slowly absorbed under tongue is better than swallowing B12 in pill form. But with a lozenge are you not also swallowing a lot of the product with your saliva and wasting it? As I have been advised sublingual is best do you recommend I purchase your methyl B12 lozenge? would that be correct?
2) Is it necessary to take other supplements with it for it to work properly for eg. folic acid and b6? and if so what doses do I need with daily B12 (1000) lozenge?
Thank you for any advice . . .kind regards,

Your question highlights one of the more common misconceptions in the nutritional supplement field, i.e. that sublingual vitamin B12 is superior to other oral dosage forms. It’s amazing how so many health food store clerks and so-called nutritionists continue to perpetuate this idea.
Here is how it started. One of the major causes of vitamin B12 deficiency is malabsorption, and one of the most notorious forms of vitamin B12 malabsorption is pernicious anemia. A substance secreted by cells in the stomach, intrinsic factor, is needed for the normal absorption of vitamin B12. When this substance is not present, as is the case in pernicious anemia, a vitamin B12 deficiency occurs. At one time, the only way to overcome this was thought to be the administration of vitamin B12 by injection, which, of course, bypasses the need for “intrinsic factor,” and absorption from the gut.
Well, you cannot sell injectable vitamin B12 in the health food store, so some clever marketing guy came up with another idea for getting around the absorption problem–sublingual absorption! What a great idea. You can bypass the malabsorption problem by having the substance be absorbed directly from under the tongue. Sublingual vitamin B12 was thus born, and has become a very popular type of nutritional supplement.
There is only one problem. Vitamin B12 is not absorbed sublingually.
Sublingual absorption works for small molecules, not large ones, and vitamin B12 is a very large molecule.
It turns out, however, that subsequent research revealed that even people with pernicious anemia can, in fact, benefit from oral vitamin B12. The trick is that they need to take very high dosages. If they do this, enough will be absorbed in spite of the malabsorption problems. Since B12 is inexpensive, and “high dosage” is still very small compared to other vitamins (micrograms vs milligrams), this is easy to accomplish.
So what about sublingual, or lozenge-forms of vitamin B12? It turns out that they work, but only because you end up swallowing the vitamin B12 as the lozenge dissolves, allowing it to be absorbed in the gut just as if it was a normal tablet or capsule.
You were concerned that swallowing the vitamin B12 was “wasting it.” Ironically, the opposite is true.
Buy a lozenge if you wish, but don’t be misled into thinking it will result in sublingual absorption. What is important is that it is a high dose.
The methyl cobalamin (Methyl B12) form is thought to be better absorbed than the regular form of B12, and I see no reason not to use it. Jarrow (and others) makes a 5,000 mcg dosage, however, as well as a 1,000 mcg dose, and I would opt for the higher dose. . .

Addendum #2
Excerpt from package insert: Nascobal Nasal Spray (Par Pharmaceutical Companies, Inc. Spring Valley, NY, 10977)
A three way crossover study in 25 fasting healthy subjects was conducted to compare the bioavailability of the B12 nasal spray to the B12 nasal gel and to evaluate the relative bioavailability of the nasal formulations as compared to the intramuscular injection. The peak concentrations after administration of intranasal spray were reached in 1.25 +/- 1.9 hours. The average peak concentration of B12 obtained after baseline correction following administration of intranasal spray was 757.96 +/- 532.17 pg/mL. The bioavailability of the nasal spray relative to the intramuscular injection was found to be 6.1%. The bioavailability of the B12 nasal spray was found to be 10% less than the B12 nasal gel. The 90% confidence intervals for the loge - transformed AUC(0-t) and Cmax was 71.71% - 114.19% and 71.6% - 118.66% respectively.
In pernicious anemia patients, once weekly intranasal dosing with 500 mcg B12 gel resulted in a consistent increase in pre-dose serum B12 levels during one month of treatment (p < 0.003) above that seen one month after 100 mcg intramuscular dose (Figure).”

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