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How Recommendations Were Formulated

Contents

• Step 1.
  • Oral B12 for People with Malabsorption
• Step 2.
  • Fortified Foods
  • Supplements
  • Sublingual
  • References

Step 1.

If you have had a regular source of B12, skip to Step 2.

If you have not had a regular source of B12 for some time, buy a bottle of sublingual B12. Place 2,000 µg under your tongue until the tablet(s) has dissolved, once a day, for 2 weeks. Then follow the advice under Step #2. (Note: you can break the remaining tablets in half or quarters for Step #2. It's okay to take more than recommended.)

These recommendations about how to replenish one's B12 stores are based on the success that people with B12 malabsorption problems have had with oral B12 supplements (as described next).

Oral B12 for People with Malabsorption

Intramuscular injections (IMI) of B12 are the typical way to treat B12 deficiency. The injections can be painful and expensive. Norberg (1) (1999, Sweden) points out that investigations in the 1950s and 60s showed that oral B12 is absorbed by an alternative pathway not dependent on intrinsic factor or an intact ileum. Approximately 1% of an oral dose in the range of 200-2000 µg/day was absorbed by the alternative pathway in those investigations. Based on this research, oral treatment, rather than IMI, has been in use for the majority of B12 deficiency cases in Sweden since the early 1970s.

Table 1. B12 Oral Administration Vs. Injection (Kuzminski et al.)
	Serum B12 (pg/ml)	Serum MMA (µmol/l)	HCY (µmol/l)
Pretreatment
Oral	93	3.85	37.2
Injection	95	3.63	40
After 4 months
Oral 2000 µg/day	1005a	.169b	10.6
Injection	325a	.265b	12.2
a,b - Statistically significant difference between groups with same letters

In a literature review encouraging the use of oral B12 therapy over injections for patients with pernicious anemia, Lederle (2) (1991, USA) reported that Swedish investigators recommend 2000 µg of oral B12 twice a day or injections to replenish B12 stores. After initial therapy, doses of 1000 µg/day appear to be enough.

Kuzminski et al (3). (1998, USA) studied 33 newly diagnosed B12-deficient patients (almost all had malabsorption) who received cyanocobalamin as either 1 mg intramuscularly on days 1, 3, 7, 10, 14, 21, 30, 60, and 90; or 2000 µg orally on a daily basis for 120 days (4 months). See Table 1.

Kuzminski et al. conclude that 2000 µg/day of oral cyanocobalamin was as effective as 1000 µg injected intramuscularly each month, and may be superior.

Delpre & Stark (4) (1999, Israel) studied patients with B12 deficiency to see if B12 can be absorbed by holding a tablet under the tongue, known as sublingual. The theory behind sublingual is that the mucous membranes under the tongue are efficient at absorbing certain molecules, particularly if combined with something fat soluble such as a cyclodextrin. 5 patients had pernicious anemia, 7 were vegetarians, and 2 had Crohn's disease (which can prevent the absorption of B12 in the ileum). The patients held two 1000 µg B12 tablets (equaling 2,000 µg/day), made by Solgar, under their tongues for 30 minutes until completely dissolved. This was done for 7 to 12 days. Average serum B12 levels went from 127.9 ± 42.6 to 515.7 ± 235. All patients' serum B12 normalized. There were no side effects and all patients preferred this to injections. Unfortunately, Delpre & Stark did not include a control group who chewed the B12 tablets, so there is no way to know if taking the tablets sublingually was more effective than chewing and swallowing them. On the basis of Kuzminski et al. above, chewing seems to be as effective if done for 3 months.

Please note that the large doses mentioned in this section are for people with B12 malabsorption (or vegans who have neglected their B12 intake for a few months). People without malabsorption problems or current B12 deficiency do not need such large doses; hence Step 2 of the recommendations.

Step 2

If you have had a regular source of B12, skip Step 1. One of these three recommendations should maximize your B12 status:

• Fortified Foods
  • Twice per day: 2.0 - 3.5 µg
• Supplements
  • Daily: 25 - 100 µg
  • Twice per week: 1,000 µg

Fortified Foods

The current U.S. RDA for vitamin B12 is 2.4 µg (6). However, this RDA was based on how much B12 is needed to prevent macrocytic anemia rather than how much is needed for ideal homocysteine or methylmalonic acid levels. Recently, research has been indicating a need for more B12 than the current RDA.

A 2010 paper by Bor et al. (13), showed that in healthy people aged 18-50, a vitamin B12 intake of 4 to 7 µg/day was associated with the lowest methylmalonic acid and homocysteine levels (6). They reviewed other research from the past 10 years, primarily on older populations, that indicates the ideal B12 intake is 6 to 10 µg/day. Their review covered the following papers:

Vitamin B12 is more easily absorbed from fortified foods (because it is not bound to protein), so vegans will not need quite as high an intake as meat-eaters. Because of this, I will not distinguish between the ages for vegans, who are getting all their B12 from fortified foods or supplements.

Of the papers above, Bor et al. (2006) and Vogiatzoglou et al. (2009) correlated B12 intake to methylmalonic acid (MMA) and homocysteine (HCY). They found that 6 and 6-10 µg/day, respectively, were associated with the lowest levels of MMA and HCY. Because these were older populations whose protein-bound B12 ability was probably decreased, and because, according to the Institute of Medicine, absorption of non-protein-bound B12 does not appear to decrease with age (6), I will stick with Bor et al.'s 2010 finding which were on people ages 18 to 50.

Note: Fortified foods represented 29% of intake in the Bor et al. (2010) study.

According to the Institute of Medicine, the second of two doses of B12 eaten 4-6 hours apart is absorbed as well as the first (6).

Therefore, a straight calculation that vegans need at least 2 doses of 2 µg per serving per day is easy to make. If you cannot find fortified foods with 2 µg per serving, you should eat more servings or take supplements.

Supplements

Unlike the studies above that measured B12 intakes from food and compared it to MMA and HCY levels, there is little research looking what level of supplements people need.

Table 2. B12 Levels in India (2010) Study
	2 µg B12 / day	10 µg B12 / day
Plasma Hcy (µmol/l)
Baseline	19.7	18.5
4 months	14.2	12.9
12 months	12.9	11.6

Instead, we will have to primarily extrapolate from known absorption rates to get the ideal levels of small-dose supplements that will be linked to the lowest MMA and HCY levels.

There is one study from India (2010) in which subjects, who were vegetarian and somewhat B12-deficient with high homocysteine levels, were given doses of either 2 µg or 10 µg of B12 each day for a year (12). See Table 2.

While both doses lowered homocysteine, neither 2 µg nor 10 µg was enough to lower it to an ideal level of less than 8 mmol/l.

Table 3. B12 Absorption Rates
Food / Oral Dose	% absorbed	µg absorbed (avg)c
fortified milk5	65%a
fortified bread5	55%
mutton5	65%
chicken5	60%
trout5	39%
eggs5	24-36%
liver6	11%
.1 µg 7	77%	0.08
.25 µg7	75%	0.19
.5 µg7,8	71-90%	.35-.45 (.4)
.6 µg7	63%	0.38
1 µg6-9	50-80%	.5-.8 (.6)
2 µg7-9	40-50%	.8-1 (.9)
5 µg6-10	20-55%	1-2.8 (1.7)
107,9	15-16%	1.5-1.6
25 µg6	5%	1.25
50 µg8,9	3%	1.5 (1.5)
1,000 µg6,8	1-1.5%b	10-15 (12.5
aNumber represents only the fortified portion of B12 in the milk | bEven without intrinsic factor | cAverage of all measurements (i.e., not the mid-range)

Russell et al. (5) (2001, Boston, MA) measured B12 absorption rates from milk and bread fortified with .1 µg B12, in healthy people who were over age 60 and had normal stomach acid (results are in the table below). Absorption rates of different doses of cyanocobalamin have also been measured and appear in Table 3.

The data in the table is somewhat mixed. A 5 µg supplemental dose of cyanocobalamin appears to saturate the intrinsic factor absorption mechanism. Thus, B12 absorption drops to 1-1.5% for any additional B12 ingested above 5 µg. But in the results in the table, the total amount absorbed from 5 to 50 µg is all about the same.

Considering all the evidence, I think we should assume that absorbing 2 to 3 µg per day is ideal. Depending on how you calculate the absorption rates, to get the same absorption rates from supplements in one dose, you would need 25 µg to 240 µg per day (11).

Because this is so imprecise and because it seems way too high that someone would need 240 µg per day, I will adjust these to 25 µg to 100 µg. The anecdotal evidence I'm aware of is that no one getting this much B12 has had any problems with deficiency symptoms.

Some people like to take large dose supplements, so let's do the math on those. The people in Bor et al. (2010) were absorbing 14 to 24.5 µg of B12 per week. If you assume a 12.5% absorption rate from high dose supplements, you would need 1,120 to 1,960 µg per week. To be safe, I would recommend 1,000 µg twice per week.

Sublingual

There appears to be no published research comparing sublingual B12 absorption rates to just chewing and swallowing immediately. It is possible that B12 is better absorbed when taken sublingually, but until research is published, we should not assume this. Recommendations given in this article are based on absorption rates of B12 that is swallowed.

While it's preferable to chew or crush a B12 tablet, powdered B12 in a capsule should be absorbed just fine if swallowed whole.

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References