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Appendix: How Recommendations were Formulated
Step 1
Step 1 states:
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. Norberg1 (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 70s.
In a literature review encouraging the use of oral B12 therapy over injections for patients with pernicious anemia, Lederle2 (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. 58
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). Results were:
Results of 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
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 & Stark4 (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, swallowing 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.
Notes for Oral B12 for People with Malabsorption
1. Norberg B. Turn of tide for oral vitamin B12 treatment. J Intern Med. 1999 Sep;246(3):237-8.
2. Lederle FA. Oral cobalamin for pernicious anemia. Medicine’s best kept secret? JAMA. 1991 Jan 2;265(1):94-5.
3. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998 Aug 15;92(4):1191-8.
4. Delpre G, Stark P, Niv Y. Sublingual therapy for cobalamin deficiency as an alternative to oral and parenteral cobalamin supplementation. Lancet. 1999 Aug 28;354(9180):740-1.
Step 2
Step 2 states:
One of the following daily recommendations should maximize your B12 status:
From fortified foods 3-5 µg
From 1 daily supplement 10-100 µg
From 2 daily supplements spaced at least 6 hours apart 5 µg
Absorption Rates of B12
Russell et al.1 (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 the table below.
B12 Absorption Rates
Food / Oral Dose % absorbed µg absorbed (avg)C
fortified milk1 65%A
fortified bread1 55%
mutton1 65%
chicken1 60%
trout1 39%
eggs1 24-36%
liver2 11%
.1 µg 3 77% 0.08
.25 µg3 75% 0.19
.5 µg3,4 71-90% .35-.45 (.4)
.6 µg3 63% 0.38
1 µg2,3,4,5 50-80% .5-.8 (.6)
2 µg3,4,5 40-50% .8-1 (.9)
5 µg2,3,4,5,6 20-55% 1-2.8 (1.7)
103,5 15-16% 1.5-1.6
25 µg2 5% 1.25
50 µg4,5 3% 1.5 (1.5)
1,000 µg2,4 1-1.5%B 10-15 (12.5)
A - Number represents only the fortified portion of B12 in the milk
B - Even without intrinsic factor
C - Average of all measurements (i.e., not the mid-range)
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.
The second of two doses given 4-6 hours apart is absorbed as well as the first.2 Absorption of non-protein-bound B12 does not appear to decrease with age.2
There appears to be no published research comparing sublingual B12 absorption rates to oral (swallowing). It is possible that B12 is better absorbed when taken sublingually, but until research is published, we should not assume this. Thus, the recommendations given in this article are based on absorption rates of B12 that is swallowed.
Notes for Absorption Rates of B12
1. Russell RM, Baik H, Kehayias JJ. Older men and women efficiently absorb vitamin B-12 from milk and fortified bread. J Nutr. 2001 Feb;131(2):291-3.
2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 2000.
3. Mollin DL. Radioactive vitamin B12 in the study of blood diseases. Brit Med Bull. 1959;15(1):8-13.
4. Estren S, Brody EA, Wasserman LR. The metabolism of vitamin B12 in pernicious and other megaloblastic anemias. Adv Intern Med. 1959;9:11.
5. Chanarin I. The Megaloblastic Anemias 3rd Ed. Oxford, UK: Blackwell Scientific Publications; 1990.
6. Heyssel RM, Bozian RC, Darby WJ, Bell MC. Vitamin B12 turnover in man. The assimilation of vitamin B12 from natural foodstuff by man and estimates of minimal daily dietary requirements. Am J Clin Nutr. 1966 Mar;18(3):176-84.
What Is a Healthy B12 Level?
Assuming that absorption is good, meeting the RDA of 2.4 µg for adults should keep macrocytic anemia from occurring. In 4 Indian vegetarians with B12-deficient anemia, .10 - .25 µg of B12 (through the diet) was not enough to correct anemia, while .3-.65 was enough.1 Not all patients, however, require so little. Studies have shown that 1.5 µg/day of injected B12 covers the needs of almost all patients with pernicious anemia.2 In fact, the RDA for B12 intake for adults is based on this number.2 However, I’m not convinced that meeting the RDA for B12 is enough to keep everyone’s homocysteine (HCY) and methylmalonic acid levels in check, and to minimize DNA damage and nerve problems. Consider these findings:
German vegans who were getting some (the exact amount was not quantified) vitamin B12 through supplements, had an average serum B12 level of 259 pg/ml. These levels were not enough to keep their homocysteine levels low. Their homocysteine levels were 11.1 µmol/l, with below 8 being ideal.6 On the other hand, U.S. vegans who supplemented with B12 had an average serum B12 level of 421 pg/ml and average homocysteine levels of 7.9 µmol/l.7
Selhub et al.3 analyzed data from 8083 people, including whites, blacks, and Hispanics, and found that elevated homocysteine levels (> 11.4 for men, > 10.4 µmol/l for women) were associated with serum B12 levels less than 338 pg/ml.
Fenech4 studied folate and B12 levels and intake in respect to DNA damage in white blood cells (lymphocytes) which, according to Fenech, has been shown to be a good marker for future cancer. They found that serum B12 > 405 pg/ml and a supplemental intake of 7 µg of B12/day were optimal for reducing DNA damage. Fenech says that folate and B12 intakes 3.5 times higher than the U.S. RDA minimize DNA damage. However, Fenech did not measure B12 intake from food, so not enough information was provided to determine the amount of B12 absorbed. It can be assumed that about 1.5 µg was absorbed from the 7 µg supplement; thus, more than 1.5 µg must have been absorbed per day (given that the subjects also had a normal dietary intake of B12) in order to minimize DNA damage.
Lindenbaum et al.5 studied MMA and HCY levels in 548 elderly people from the Framingham Heart Study (Table L.2.2). The authors chose a serum B12 level of 350 pg/ml as the lower limit for suspecting a B12 deficiency because so many subjects with levels below this limit had elevated levels of sMMA:
Results of Lindenbaum et al.
Number Number with MMA
> .376 µmol/l Number with
MMA > .376 µmol/l
& HCY > 21.3 µmol/l % taking B12 SUPB
(reporting)
sB12 < 350 222 62 (28%) 21 (9%) 12% (160)
sB12 > 350 326 20 (6%)A 4 (1%) 40% (241)
A - At least 10 subjects had elevated MMA due to poor kidney function, putting the number closer to 10 (3%)
B - Median amount of B12 in supplements was 6 µg
SUP - supplement
Based on the above research, serum B12 levels of 338 - 405 pg/ml seem necessary to limit damage.
Notes for What Is a Healthy B12 Level?
1. Baker SJ, Mathan VI. Evidence regarding the minimal daily requirement of dietary vitamin B12. Am J Clin Nutr. 1981 Nov;34(11):2423-33.
2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 2000.
3. Selhub J, Bagley LC, Miller J, Rosenberg IH. B vitamins, homocysteine, and neurocognitive function in the elderly. Am J Clin Nutr. 2000 Feb;71(2):614S-620S.
4. Fenech M. Micronucleus frequency in human lymphocytes is related to plasma vitamin B12 and homocysteine. Mutat Res. 1999 Jul 16;428(1-2):299-304.
5. Lindenbaum J, Rosenberg IH, Wilson PW, Stabler SP, Allen RH. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr. 1994 Jul;60(1):2-11.
6. Herrmann W, Schorr H, Obeid R, Geisel J. Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J Clin Nutr. 2003 Jul;78(1):131-6.
7. Haddad EH, Berk LS, Kettering JD, Hubbard RW, Peters WR. Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians. Am J Clin Nutr. 1999;70(suppl):586S-93S.
B12 Intake Needed to Achieve a Healthy Level
Tucker et al.1 (2000, USA) examined the B12 status of 2999 subjects in the Framingham Offspring Study. Serum B12 was associated with B12 intake. Based on Figure 1 in Tucker et al.,1 2 µg from foods (at a 50% absorption rate) should keep one’s serum B12 levels at about 350 pg/ml. An intake of about 5 µg from foods (at a 50% absorption rate) keeps serum B12 levels at about 430 pg/ml, a level at which people rarely, if ever, have B12-related problems (and which covers Fenech’s findings on DNA damage above). This translates into 2.5 µg/day being absorbed.
Based on rates listed in the table above, B12 Absorption Rates, the table below lists the amounts of B12 needed from fortified foods and supplements to match the intakes extrapolated from Tucker et al.1
B12 Intake Needed to Achieve a Given Serum B12 Level
Serum B12 target ~ 350 pg/ml ~ 430 pg/ml OtherB
Intake/day per Tucker et al.1 2 µg 5 µg
Absorbed per day at a 50% rate 1 µg 2.5 µg
Amount needed to equal above amounts absorbed:
Fortified foods throughout the day 2 µg 5 µg 3 µg
1 daily SUP 2-5 µgE 100 µg 10 µg
1 SUP, 2x dailyA 2 µg 4-5 µgE
1 weekly cyanocobalamin supplementC,D 700 µg 1700 µg 2000 µg
A - Spaced 6 hours apart
B - Minimum recommended amounts by vegan health professionals in What Every Vegan Should Know about Vitamin B12
C - Chewed or sublingual
D - Based on 1% absorption rate
E - Absorption rates in doses of between 2 and 5 µg are not known
Absorption Rate Calculation Example: Amount Needed to Absorb 2.5 µg
At a 5 µg dose, about 1.5 µg is absorbed.
About 1% is absorbed of anything above 5 µg.
By adding 1.5 µg absorbed from the first 5 µg of a cyanocobalamin supplement, plus .1 µg for each additional 10 µg increment (.01 * 10 µg), we can compile enough B12 to equal 2.5 µg absorbed:
2.5 µg needed - 1.5 µg (from the first 5 µg of a given dose) = 1.0 µg remaining to be absorbed
1.0 µg remaining / .1 µg (amount absorbed from an additional 10 µg dose) = 10 (doses of 10 µg needed)
10 remaining doses * 10 µg = 100 µg
100 µg + (the first) 5 µg = 105 µg total
Because 100 µg translates into 2.4 µg absorbed, which is almost the same as 2.5 µg, 105 µg can be rounded down to 100 µg.
Notes for B12 Intake Needed to Achieve a Healthy Level
1. Tucker KL, Rich S, Rosenberg I, Jacques P, Dallal G, Wilson PW, Selhub J. Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study. Am J Clin Nutr. 2000 Feb;71(2):514-22.
Minimum Recommendations
In What Every Vegan Should Know about Vitamin B12, minimum recommendations are given for vegans:
3 µg from fortified foods
1 daily 10 µg supplement
1 weekly 2000 µg supplement
As can be seen from the table above, B12 Intake Needed to Achieve a Given Serum B12 Level, these recommendations should put B12 levels between 350 and 430 pg/ml. Thus, for consistency with other vegan health professionals, I have used them as minimum amounts.
Step 2: Conclusion
Taking a weekly supplement, to keep B12 levels up and homocysteine levels down, has not been tested. For this reason, I am more in favor of the fortified foods and daily supplement options.
Some people may wonder what levels are ideal, rather than minimal (assuming one does not suffer from intrinsic-factor-related problems). Thus I have suggested a range above which should provide no further benefit and below which there is evidence of at least modest adverse effects. My final recommendations to keep B12 levels between 350-430 pg/ml are:
From fortified foods 3-5 µg
From 1 daily supplement 10-100 µg
From 2 daily supplements spaced at least 6 hours apart 5 µg
Appendix: How Recommendations were Formulated
Step 1
Step 1 states:
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. Norberg1 (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 70s.
In a literature review encouraging the use of oral B12 therapy over injections for patients with pernicious anemia, Lederle2 (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. 58
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). Results were:
Results of 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
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 & Stark4 (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, swallowing 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.
Notes for Oral B12 for People with Malabsorption
1. Norberg B. Turn of tide for oral vitamin B12 treatment. J Intern Med. 1999 Sep;246(3):237-8.
2. Lederle FA. Oral cobalamin for pernicious anemia. Medicine’s best kept secret? JAMA. 1991 Jan 2;265(1):94-5.
3. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998 Aug 15;92(4):1191-8.
4. Delpre G, Stark P, Niv Y. Sublingual therapy for cobalamin deficiency as an alternative to oral and parenteral cobalamin supplementation. Lancet. 1999 Aug 28;354(9180):740-1.
Step 2
Step 2 states:
One of the following daily recommendations should maximize your B12 status:
From fortified foods 3-5 µg
From 1 daily supplement 10-100 µg
From 2 daily supplements spaced at least 6 hours apart 5 µg
Absorption Rates of B12
Russell et al.1 (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 the table below.
B12 Absorption Rates
Food / Oral Dose % absorbed µg absorbed (avg)C
fortified milk1 65%A
fortified bread1 55%
mutton1 65%
chicken1 60%
trout1 39%
eggs1 24-36%
liver2 11%
.1 µg 3 77% 0.08
.25 µg3 75% 0.19
.5 µg3,4 71-90% .35-.45 (.4)
.6 µg3 63% 0.38
1 µg2,3,4,5 50-80% .5-.8 (.6)
2 µg3,4,5 40-50% .8-1 (.9)
5 µg2,3,4,5,6 20-55% 1-2.8 (1.7)
103,5 15-16% 1.5-1.6
25 µg2 5% 1.25
50 µg4,5 3% 1.5 (1.5)
1,000 µg2,4 1-1.5%B 10-15 (12.5)
A - Number represents only the fortified portion of B12 in the milk
B - Even without intrinsic factor
C - Average of all measurements (i.e., not the mid-range)
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.
The second of two doses given 4-6 hours apart is absorbed as well as the first.2 Absorption of non-protein-bound B12 does not appear to decrease with age.2
There appears to be no published research comparing sublingual B12 absorption rates to oral (swallowing). It is possible that B12 is better absorbed when taken sublingually, but until research is published, we should not assume this. Thus, the recommendations given in this article are based on absorption rates of B12 that is swallowed.
Notes for Absorption Rates of B12
1. Russell RM, Baik H, Kehayias JJ. Older men and women efficiently absorb vitamin B-12 from milk and fortified bread. J Nutr. 2001 Feb;131(2):291-3.
2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 2000.
3. Mollin DL. Radioactive vitamin B12 in the study of blood diseases. Brit Med Bull. 1959;15(1):8-13.
4. Estren S, Brody EA, Wasserman LR. The metabolism of vitamin B12 in pernicious and other megaloblastic anemias. Adv Intern Med. 1959;9:11.
5. Chanarin I. The Megaloblastic Anemias 3rd Ed. Oxford, UK: Blackwell Scientific Publications; 1990.
6. Heyssel RM, Bozian RC, Darby WJ, Bell MC. Vitamin B12 turnover in man. The assimilation of vitamin B12 from natural foodstuff by man and estimates of minimal daily dietary requirements. Am J Clin Nutr. 1966 Mar;18(3):176-84.
What Is a Healthy B12 Level?
Assuming that absorption is good, meeting the RDA of 2.4 µg for adults should keep macrocytic anemia from occurring. In 4 Indian vegetarians with B12-deficient anemia, .10 - .25 µg of B12 (through the diet) was not enough to correct anemia, while .3-.65 was enough.1 Not all patients, however, require so little. Studies have shown that 1.5 µg/day of injected B12 covers the needs of almost all patients with pernicious anemia.2 In fact, the RDA for B12 intake for adults is based on this number.2 However, I’m not convinced that meeting the RDA for B12 is enough to keep everyone’s homocysteine (HCY) and methylmalonic acid levels in check, and to minimize DNA damage and nerve problems. Consider these findings:
German vegans who were getting some (the exact amount was not quantified) vitamin B12 through supplements, had an average serum B12 level of 259 pg/ml. These levels were not enough to keep their homocysteine levels low. Their homocysteine levels were 11.1 µmol/l, with below 8 being ideal.6 On the other hand, U.S. vegans who supplemented with B12 had an average serum B12 level of 421 pg/ml and average homocysteine levels of 7.9 µmol/l.7
Selhub et al.3 analyzed data from 8083 people, including whites, blacks, and Hispanics, and found that elevated homocysteine levels (> 11.4 for men, > 10.4 µmol/l for women) were associated with serum B12 levels less than 338 pg/ml.
Fenech4 studied folate and B12 levels and intake in respect to DNA damage in white blood cells (lymphocytes) which, according to Fenech, has been shown to be a good marker for future cancer. They found that serum B12 > 405 pg/ml and a supplemental intake of 7 µg of B12/day were optimal for reducing DNA damage. Fenech says that folate and B12 intakes 3.5 times higher than the U.S. RDA minimize DNA damage. However, Fenech did not measure B12 intake from food, so not enough information was provided to determine the amount of B12 absorbed. It can be assumed that about 1.5 µg was absorbed from the 7 µg supplement; thus, more than 1.5 µg must have been absorbed per day (given that the subjects also had a normal dietary intake of B12) in order to minimize DNA damage.
Lindenbaum et al.5 studied MMA and HCY levels in 548 elderly people from the Framingham Heart Study (Table L.2.2). The authors chose a serum B12 level of 350 pg/ml as the lower limit for suspecting a B12 deficiency because so many subjects with levels below this limit had elevated levels of sMMA:
Results of Lindenbaum et al.
Number Number with MMA
> .376 µmol/l Number with
MMA > .376 µmol/l
& HCY > 21.3 µmol/l % taking B12 SUPB
(reporting)
sB12 < 350 222 62 (28%) 21 (9%) 12% (160)
sB12 > 350 326 20 (6%)A 4 (1%) 40% (241)
A - At least 10 subjects had elevated MMA due to poor kidney function, putting the number closer to 10 (3%)
B - Median amount of B12 in supplements was 6 µg
SUP - supplement
Based on the above research, serum B12 levels of 338 - 405 pg/ml seem necessary to limit damage.
Notes for What Is a Healthy B12 Level?
1. Baker SJ, Mathan VI. Evidence regarding the minimal daily requirement of dietary vitamin B12. Am J Clin Nutr. 1981 Nov;34(11):2423-33.
2. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 2000.
3. Selhub J, Bagley LC, Miller J, Rosenberg IH. B vitamins, homocysteine, and neurocognitive function in the elderly. Am J Clin Nutr. 2000 Feb;71(2):614S-620S.
4. Fenech M. Micronucleus frequency in human lymphocytes is related to plasma vitamin B12 and homocysteine. Mutat Res. 1999 Jul 16;428(1-2):299-304.
5. Lindenbaum J, Rosenberg IH, Wilson PW, Stabler SP, Allen RH. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr. 1994 Jul;60(1):2-11.
6. Herrmann W, Schorr H, Obeid R, Geisel J. Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J Clin Nutr. 2003 Jul;78(1):131-6.
7. Haddad EH, Berk LS, Kettering JD, Hubbard RW, Peters WR. Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians. Am J Clin Nutr. 1999;70(suppl):586S-93S.
B12 Intake Needed to Achieve a Healthy Level
Tucker et al.1 (2000, USA) examined the B12 status of 2999 subjects in the Framingham Offspring Study. Serum B12 was associated with B12 intake. Based on Figure 1 in Tucker et al.,1 2 µg from foods (at a 50% absorption rate) should keep one’s serum B12 levels at about 350 pg/ml. An intake of about 5 µg from foods (at a 50% absorption rate) keeps serum B12 levels at about 430 pg/ml, a level at which people rarely, if ever, have B12-related problems (and which covers Fenech’s findings on DNA damage above). This translates into 2.5 µg/day being absorbed.
Based on rates listed in the table above, B12 Absorption Rates, the table below lists the amounts of B12 needed from fortified foods and supplements to match the intakes extrapolated from Tucker et al.1
B12 Intake Needed to Achieve a Given Serum B12 Level
Serum B12 target ~ 350 pg/ml ~ 430 pg/ml OtherB
Intake/day per Tucker et al.1 2 µg 5 µg
Absorbed per day at a 50% rate 1 µg 2.5 µg
Amount needed to equal above amounts absorbed:
Fortified foods throughout the day 2 µg 5 µg 3 µg
1 daily SUP 2-5 µgE 100 µg 10 µg
1 SUP, 2x dailyA 2 µg 4-5 µgE
1 weekly cyanocobalamin supplementC,D 700 µg 1700 µg 2000 µg
A - Spaced 6 hours apart
B - Minimum recommended amounts by vegan health professionals in What Every Vegan Should Know about Vitamin B12
C - Chewed or sublingual
D - Based on 1% absorption rate
E - Absorption rates in doses of between 2 and 5 µg are not known
Absorption Rate Calculation Example: Amount Needed to Absorb 2.5 µg
At a 5 µg dose, about 1.5 µg is absorbed.
About 1% is absorbed of anything above 5 µg.
By adding 1.5 µg absorbed from the first 5 µg of a cyanocobalamin supplement, plus .1 µg for each additional 10 µg increment (.01 * 10 µg), we can compile enough B12 to equal 2.5 µg absorbed:
2.5 µg needed - 1.5 µg (from the first 5 µg of a given dose) = 1.0 µg remaining to be absorbed
1.0 µg remaining / .1 µg (amount absorbed from an additional 10 µg dose) = 10 (doses of 10 µg needed)
10 remaining doses * 10 µg = 100 µg
100 µg + (the first) 5 µg = 105 µg total
Because 100 µg translates into 2.4 µg absorbed, which is almost the same as 2.5 µg, 105 µg can be rounded down to 100 µg.
Notes for B12 Intake Needed to Achieve a Healthy Level
1. Tucker KL, Rich S, Rosenberg I, Jacques P, Dallal G, Wilson PW, Selhub J. Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study. Am J Clin Nutr. 2000 Feb;71(2):514-22.
Minimum Recommendations
In What Every Vegan Should Know about Vitamin B12, minimum recommendations are given for vegans:
3 µg from fortified foods
1 daily 10 µg supplement
1 weekly 2000 µg supplement
As can be seen from the table above, B12 Intake Needed to Achieve a Given Serum B12 Level, these recommendations should put B12 levels between 350 and 430 pg/ml. Thus, for consistency with other vegan health professionals, I have used them as minimum amounts.
Step 2: Conclusion
Taking a weekly supplement, to keep B12 levels up and homocysteine levels down, has not been tested. For this reason, I am more in favor of the fortified foods and daily supplement options.
Some people may wonder what levels are ideal, rather than minimal (assuming one does not suffer from intrinsic-factor-related problems). Thus I have suggested a range above which should provide no further benefit and below which there is evidence of at least modest adverse effects. My final recommendations to keep B12 levels between 350-430 pg/ml are:
From fortified foods 3-5 µg
From 1 daily supplement 10-100 µg
From 2 daily supplements spaced at least 6 hours apart 5 µg
