Vitamin B12 Deficiency & Supplementation

[Cloud]

[Admin Note: This is a new thread to consolidate the important discussion of Vitamin B12 levels, deficiency and supplementation started by Cloud in this thread originally by Zeta on his Extreme blood values. The topic of B12 deficiency, particularly for CR Practitioners who don't generally consume a lot of meat, deserves its own thread. -Dean]

 

 

Hi Zeta,

 

"But since I started taking one of these NatureMade iron supplements per day (361% RDA) I haven't had any trouble with anemia symptoms. Yes, 361% of the RDA on top of the food I eat is a lot of iron, but my hemoglobin and ferritin (measure of stored iron level) remain at or below the reference range despite the megadosing. I will say that despite getting >100% of the RDA for iron from my diet (albeit in non-heme form), when I haven't supplemented iron on top of my dietary intake I've slipped into anemia on several occasions. It appears my body can't/won't absorb or store a whole lot of iron. 

 

Do you supplement with iron? In the past, taking one (and ocassionally two) of the above referenced supplements per day for a few weeks has cleared up my anemia symptoms - weakness (aka 'heavy legs' feeling), out of breath exercising / climbing stairs, and low hemoglobin level.

 

--Dean

 

Hello, can I ask a question? What happens if the body can't absorb the iron from diet? I am asking about the relationship between serum iron and ferritin.

In March I had serum iron at 134 mcg/dL, ferritin at 71.30 mcg/dL (and B12 very low 79 mcg/dL)  , now at the latest analysis serum iron is 209 mcg/dL and ferritin is 96.60 mcg/dL and because I am supplementing B12 is 156.  I am wondering what mean this so high serum iron. Could it come from food containing iron that I can not absorb? In the last months the only foods, containing much iron I introduced as new, was pistachios and dark chocolate. I also, as some of you, drink about 1 L/day of green tea, that should limit a lot iron absorption. I still have to show this data to my doctor. Thanks!

Edited November 25, 2015 by Dean Pomerleau
Added note to announce new thread.

[nicholson]

Hi Cloud:

 

In case you did not see my comments on B12 in another thread:  I would view 79 as alarming.  My 123 was associated with what others described as disturbing symptoms.  And, imo, your 156 is no cause for celebration either.  It has been found in Japan that some people are deficient B12 even with a blood level of 300 (the blood level of B12 is NOT the definitive test for B12 adequacy), so in Japan it is now suggested that a minimum acceptable blood B12 level is 400 (in US units).

 

Rodney. 

[Dean Pomerleau]

Rodney beat me to it.

 

Cloud - I agree 100% with Rodney. You should worry about your B12 level, not (so much) you iron level. I'm not sure how long you've been supplementing with B12, but regardless, you probably need to seriously up the dose if your level has only risen from 79 to 156 mcg/dL since March. B12 deficiency can result in permanent, neurological and other damage. To correct serious deficiencies such as yours often requires megadoses of B12, and perhaps injections, but at least 100 or 1000s of times the RDA. Megadoses of B12 are safe, and warranted to correct big deficiencies.

 

Seriously, you should see your doctor right away to get it corrected. Then you can worry about your iron. If you're experiencing anemia-like symptoms, it almost certainly a result of your B12 deficiency, not your iron level.

 

--Dean

 

[Cloud]

Rodney beat me to it.

 

Cloud - I agree 100% with Rodney. You should worry about your B12 level, not (so much) you iron level. I'm not sure how long you've been supplementing with B12, but regardless, you probably need to seriously up the dose if your level has only risen from 79 to 156 mcg/dL since March. B12 deficiency can result in permanent, neurological and other damage. To correct serious deficiencies such as yours often requires megadoses of B12, and perhaps injections, but at least 100 or 1000s of times the RDA. Megadoses of B12 are safe, and warranted to correct big deficiencies.

 

Seriously, you should see your doctor right away to get it corrected. Then you can worry about your iron. If you're experiencing anemia-like symptoms, it almost certainly a result of your B12 deficiency, not your iron level.

 

--Dean

Hello Rodney and Dean, thanks a lot. Actually my data was not completed (I was concentrating on iron issue). Actually after B12 value in March I took 25 mcg B12 sublingual pill supplement daily and in three months (June) B12 value went to 184 . After that I decided to change supplement (because some edulcorant I wanted to avoid) and choose a supplement with only 2.5 mcg (100 RDA) daily.. Because my diet is not completely vegan-I eat some fish or egg once week -I thought that this could be a good strategy to maintain B12 level, but I was apparently wrong because since June B12 has fell to 156 mcg/dL....

[Dean Pomerleau]

Hello Rodney and Dean, thanks a lot. Actually my data was not completed (I was concentrating on iron issue). Actually after B12 value in March I took 25 mcg B12 sublingual pill supplement daily and in three months (June) B12 value went to 184 . After that I decided to change supplement (because some edulcorant I wanted to avoid) and choose a supplement with only 2.5 mcg (100 RDA) daily.. Because my diet is not completely vegan-I eat some fish or egg once week -I thought that this could be a good strategy to maintain B12 level, but I was apparently wrong because since June B12 has fell to 156 mcg/dL....

 

Cloud,

 

Despite risking sounding rude, let me repeat myself. See a doctor to get this taken care of ASAP. You should be getting way more B12 than you are to correct your deficiency. From here:

 

Treatment

 

Treatment of clinical vitamin B12 deficiency has traditionally been accomplished by intramuscular injection of crystalline vitamin B12 at a dosage of 1 mg weekly for eight weeks, followed by 1 mg monthly for life.1,2 In a 2005 Cochrane review, patients who received high dosages of oral vitamin B12 (1 to 2 mg daily) for 90 to 120 days had an improvement in serum vitamin B12 similar to patients who received intramuscular injections of vitamin B12.20 These results were consistent in patients regardless of the etiology of their vitamin B12 deficiency, including malabsorption states and pernicious anemia. Given the lower cost and ease of administration of oral vitamin B12, this might be a reasonable choice for replacement in many patients. In cases of megaloblastic anemia, reticulocytosis generally occurs within a few days, and the hematocrit generally normalizes over several weeks.21 Advanced neurologic symptoms may not respond to replacement.1 Vitamin B12 has been demonstrated to be safe in doses up to 1,000 times the recommended dietary allowance and is safe in pregnancy.21 The bioavailability of sublingual vitamin B12 appears to be equivalent to oral vitamin B12, but there is no evidence that sublingual delivery offers any advantage over oral preparations.22

 

Notice the dosage the Cochrane review investigated to correct B12 deficiency - 1 to 2 mg oral B12 per day. You 2.5 mcg per day converts to 0.0025 mg, which is 600 times less than the recommended dosage of 1-2mg to correct a serious deficiency!

 

Seriously. Get it fixed.

 

--Dean

[nicholson]

When I supplemented B12 daily to fix my deficiency, my blood B12 went from 123 to 508 in six months.

 

But I forget now the size of dose.

 

Rodney.

[nicholson]

Incidentally, I just noticed that my 'Location' information is 'out of date for now'.  For the next couple of months it would more accurately say:

 

"The river near here empties into the Pacific Ocean, a little south of the Tropic of Cancer."

 

: ^ )))))

 

Rodney.

[James Cain]

Cloud,

 

Despite risking sounding rude, let me repeat myself. See a doctor to get this taken care of ASAP. You should be getting way more B12 than you are to correct your deficiency. 

 

...

 

Notice the dosage the Cochrane review investigated to correct B12 deficiency - 1 to 2 mg oral B12 per day. You 2.5 mcg per day converts to 0.0025 mg, which is 600 times less than the recommended dosage of 1-2mg to correct a serious deficiency!

 

Seriously. Get it fixed.

 

--Dean

 

Cloud,

 

I'll hop in and agree with the advice already given. Correcting B12 deficiency and ensuring maintenance often takes 500 mcg supplementation, which is what I've been taking for years to maintain a good mid-level B12 level. Irregardless of plasma B12, you should also be tested for methylmalonic acid (MMA)  (and about the MMA test here) and possibly homocysteine as these require B12 to be metabolized, so elevated levels indicate ineffective B12 activity. This is most often the case with B12 deficiency, but some people need higher B12 levels to properly regulate these metabolic pathways.

[nicholson]

This is a useful source on vitamin B12:

 

https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/

 

In particular, regarding the issue of dose size and frequency for this particular vitamin, the following quote, from the above link, may be helpful:

 

"Approximately 56% of a 1 mcg oral dose of vitamin B12 is absorbed, but absorption decreases drastically when the capacity of intrinsic factor is exceeded (at 1–2 mcg of vitamin B12)".

 

Two micrograms is a very small amount, so the importance of a frequent but small intake of this vitamin is clear if supplemention is necessary.  And if the japanese threshold blood level of 400 in US units is appropriate, then maybe even carnivores will need to supplement.

 

Rodney.

[keithsct]

[Admin Note: This post was moved from this thread, since this is the more appropriate home for it. - Dean]

 

Thanks for your response above, Dean.  I have to say that I'm still not willing to dump the calorie restriction portion of CRON, despite your answer.  The excellent metrics from medical tests in humans on CR will, I believe, lead to a healthier life. If I don't have to suffer at the end of life, then I think it's the right choice for me.  

 

One more question to anyone who knows the answer.  Deficiency of B12 or folate creates high homo-cysteine levels and this has been suggested to cause heart problems in many of the vegans and some vegetarians in the EPIC study.  So why isn't homo-cysteine a test that is regularly done?  This link says that 47 million americans are B12 deficient.  Is there some reason that the test for it is inaccurate, or highly variable?  I note that Private MD tests do include one for $63, so it's not awfully expensive.

[Michael R]

[Admin Note: This post was moved from this thread, since this is the more appropriate home for it. - Dean]

 

Deficiency of B12 or folate creates high homo-cysteine levels and this has been suggested to cause heart problems in many of the vegans and some vegetarians in the EPIC study.  So why isn't homo-cysteine a test that is regularly done?  This link says that 47 million americans are B12 deficient.  Is there some reason that the test for it is inaccurate, or highly variable?  I note that Private MD tests do include one for $63, so it's not awfully expensive.

 

Ugh ... Keith, please never, ever take anything you see on Natural News as having as having any relationship to reality until confirming it with a more reputable source of health information (such as Rick Perry, or your Aunt Mabel), and certainly don't cite it for anything. The page to which you link via a Google intermediary also has in the sidebar the headlines "ANALYSIS: Chipotle is a victim of corporate sabotage... biotech industry food terrorists are planting e.coli in retaliation for restaurant's anti-GMO menu" [!] and "Sacramento officials caught secretly adding cancer-causing chemicals to the water supply" (which turns out to be an extremely gross, paranoid distortion of the real underlying story, which involves the non-hidden, non-secret, and completely unintentional generation of excessive (and, yes, carcinogenic) chlorine byproducts as a secondary result of tweaking their water purification protocol in a way that required them to add more chlorine into the supply).

 

The article you link gives nothing resembling a proper citation. When I went looking, I found many rehashes of the NN story on similarly-disreputable sites, but also did find this article from a respectable-looking source. Still, when you consult her actual citation (PMID 19116323), you see that it doesn't say that at all:

 

 

In large surveys in the United States and the United Kingdom, ≈6% of those aged ≥60 y are vitamin B-12 deficient (plasma vitamin B-12 < 148 pmol/L), with the prevalence of deficiency increasing with age. Closer to 20% have marginal status (plasma vitamin B-12: 148–221 pmol/L) in later life. ... [in NHANES], The prevalence of deficiency (serum vitamin B-12 < 148 pmol/L) varied by age group and affected ≤3% of those aged 20–39 y, ≈4% of those aged 40–59 y, and ≈6% of persons aged ≥70 y. Deficiency was present in <1% of children and adolescents but was ≤3% in children aged <4 y (the youngest age group reported). Marginal depletion (serum vitamin B-12: 148–221 pmol/L) was more common and occurred in ≈14–16% of those aged 20–59 y and >20% of those >60 y.

 

It appears that all of these articles are conflating "marginal depletion" with "deficiency," and also using a source which seems to have somewhat high numbers to begin with. An article in the American Academy Physician (the members' publication of the American Academy of Family Physicians) cites much lower data from Framingham and a separate CDC analysis of NHANES data:

 

 

The true prevalence of vitamin B₁₂ deficiency is difficult to estimate because reports are based on values that vary because of inclusion criteria and individual laboratory methodology. In 1994, the Framingham Heart Study reported the prevalence of vitamin B₁₂ deficiency, as defined by a serum vitamin B₁₂ level less than 200 pg per mL and elevated levels of serum homocysteine, methylmalonic acid, or both, to be 12 percent among 548 community-dwelling older patients.6 However, most deficient patients did not have hematologic manifestations, and neurologic manifestations were not assessed. According to unpublished data from the National Health and Nutrition Examination Survey, 3.2 percent of U.S. adults older than 50 years are estimated to have a serum vitamin B₁₂ level less than 200 pg per mL.1

 

1. Evatt ML, Mersereau PW, Bobo JK, Kimmons J, Williams J. Centers for Disease Control and Prevention. Why vitamin B₁₂ deficiency should be on your radar screen. http://www.cdc.gov/ncbddd/b12/index.html. Accessed August 20, 2010. [Link is dead; Archived version here].

 

 

Serum B12 alone is an insufficient marker, but it's pretty clear that the prevalence of deficiency is way lower, and biased toward older persons and vegetarians (mostly vegans); there's no sense making any B12 test a standard screening test, and Hcy is both expensive and nonspecific, indicating either folate or B12 deficiency, or possibly other factors unrelated to vitamin status. A proper screen for functional deficiency would include Hcy, methylmalonic acid (MMA), and serum B12, and would best be targeted to the elderly, veg(etari)ans, and persons with symptoms.

 

Back to originally-scheduled programming ;) .

[Dean Pomerleau]

Michael wrote:

Hcy [Homocysteine] is both expensive and nonspecific, indicating either folate or B12 deficiency, or possibly other factors unrelated to vitamin status. 

 

Anecdotally, my GP was quite reluctant to prescribe a homocysteine test for me during my recent checkup (although I finally prevailed). He said that clinicians had high hopes a few years ago that homocysteine levels might be an independent predictor of cardiovascular disease risk, but it hasn't panned out, which I confirmed via a pubmed search I won't bore you with. He also said (as Michael did) that an elevated Hcy level isn't definitive for diagnosing B12 deficiency, although it can be helpful, particularly for those who consume B12 analogs from plant foods, which can be worse than useless.

 

BTW, for anyone interested in a novel way of getting B12 (preview - from caffeine mints), please see this new post on a related thread.

 

--Dean

[nicholson]

Hi CLOUD and DEAN:

 

Thanks, Dean for reorganizing this topic, all in one spot.  Might a capitalized subject line be appropriate for it?

 

Cloud:  regarding your "What happens if the body can't absorb the iron from diet? I am asking about the relationship between serum iron and ferritin.

In March I had serum iron at 134 mcg/dL, ferritin at 71.30 mcg/dL (and B12 very low 79 mcg/dL)  , now at the latest analysis serum iron is 209 mcg/dL and ferritin is 96.60 mcg/dL and because I am supplementing B12 is 156.  "

 

Good to see your B12 is responding to supplementation.  I mention this because in some people supplementation does not raise the blood level because the mechanism for absorbing it in the gut is impaired.  Failure to fix such a dwindling availability of B12 would ultimately be terminal.  And before the remedy was discovered, it used to be.  But these days the remedy for an inability to absorb B12 is periodic intra-muscular injections of it.

 

I add the above for completeness, so that if at some future time someone with this problem reads this thread, they will find this information.

 

Rodney.

 

===========

 

"The unverified conventional wisdom is almost invariably mistaken."

Edited December 29, 2015 by nicholson

[Dean Pomerleau]

And for even more completeness, when Cloud said:

and because I am supplementing B12 is 156. 

 

It should be pointed out to future readers of this thread that a B12 reading of 156 is still quite deficient and needs to be corrected to avoid eventual serious adverse neurological effects, since the adult reference range in the US is considered to be 200-900 pg/ml. And in Japan the reference range is 500-1300 pg/ml, which means at 440, I too would be considered deficient. Perhaps its time I ate another B12-fortified caffeine mint. 

 

--Dean

[nicholson]

.....  and for a little more completeness:

 

There is reason to suspect the japanese have done a better job than we have at analyzing the topic of B12 adequacy!

 

Rodney.

 

=====

 

"The unverified conventional wisdom is almost invariably mistaken."

[Dean Pomerleau]

Earlier I wrote:

 

[My GP] said that clinicians had high hopes a few years ago that homocysteine levels might be an independent predictor of cardiovascular disease risk, but it hasn't panned out, which I confirmed via a pubmed search I won't bore you with.

 

Well, it turns out that both my GP and I may have been wrong...

 

According to this new Cochrane meta-analysis [1] of the association between homocysteine (Hcy) and all-cause/CVD mortality posted today by Al Pater (thanks Al!), elevated homocysteine appears in fact to be a strong and independent predictor of both all-cause and cardiovascular mortality:

 

Comparing the highest to lowest homocysteine level categories, CHD mortality increased by 66% (RR 1.66; 95% CI 1.12-2.47; P=0.012), cardiovascular mortality increased by 68% (RR 1.68; 95% CI 1.04-2.70; P=0.033), and all-cause mortality increased by 93% (RR 1.93; 95% CI 1.54-2.43; P<0.001).

 

The pooled RR of all-cause mortality for the per 5 μmol/L increment serum Hcy was 1.27 (95% CI 1.03–1.33; P=0.023).

 

Those are very dramatic numbers, and it appears that the studies included in the meta analysis generally controlled for most of the major risk factors for CVD, suggesting that Hyc is indeed an independent risk factor.

 

As for the mechanism involved, here is what the authors had to say, from the free full text:

 

The mechanisms underlying Hcy levels and risk of mortality have not yet been elucidated. Experimental studies suggest that higher Hcy caused endothelial dysfunction (Celermajer et al., 1993), platelet activation and thrombus formation (Dionisio et al., 2010). Meta-analysis of prospective cohort studies demonstrated that hyperhomocysteinemia was associated with cardiovascular disease (Bautista et al., 2002), cognitive decline (Ho et al., 2011), and fracture (Yang et al., 2012). All above diseases increased death in elderly persons.

 

So I'm glad I got my homocysteine level tested, and it came out below 10 umol/L (9.2 to be exact), which was generally around the cutoff level below which homocysteine was classified as "low" in the majority of studies included in this meta-analysis.

 

--Dean

 

Elevated homocysteine levels and risk of cardiovascular and all-cause mortality: a meta-analysis of prospective studies.
Peng HY, Man CF, Xu J, Fan Y.
J Zhejiang Univ Sci B. 2015 Jan;16(1):78-86. doi: 10.1631/jzus.B1400183.
PMID: 25559959 Free PMC Article
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288948/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4288948/pdf/JZUSB16-0078.pdf

Abstract

OBJECTIVE:

To investigate whether elevated homocysteine levels were a predictor of subsequent coronary heart disease (CHD) mortality, cardiovascular mortality or all-cause mortality in the general population by a meta-analysis.

METHODS:

In a systematic search conducted in the databases of PubMed and Embase prior to October 2013, we identified relevant prospective observational studies evaluating the association between baseline homocysteine levels and CHD mortality, cardiovascular or all-cause mortality in the general population. Pooled adjust risk ratio (RR) and corresponding 95% confidence interval (CI) were calculated separately for categorical risk estimates and continuous risk estimates.

RESULTS:

Twelve studies with 23623 subjects were included in the meta-analysis. Comparing the highest to lowest homocysteine level categories, CHD mortality increased by 66% (RR 1.66; 95% CI 1.12-2.47; P=0.012), cardiovascular mortality increased by 68% (RR 1.68; 95% CI 1.04-2.70; P=0.033), and all-cause mortality increased by 93% (RR 1.93; 95% CI 1.54-2.43; P<0.001). Moreover, for each 5 µmol/L homocysteine increment, the pooled RR was 1.52 (95% CI 1.26-1.84; P<0.001) for CHD mortality, 1.32 (95% CI 1.08-1.61; P=0.006) for cardiovascular mortality, and 1.27 (95% CI 1.03-1.55; P=0.023) for all-cause mortality.

CONCLUSIONS:

Elevated homocysteine levels are an independent predictor for subsequent cardiovascular mortality or all-cause mortality, and the risks were more pronounced among elderly persons.

KEYWORDS:

All-cause mortality; Cardiovascular mortality; Coronary heart disease; Homocysteine; Meta-analysis

[Michael R]

All:

I began drafting this post shortly after Dean's last one of 30 December 2015, and then dropped it due to the digging required to complete it ... here is the most important bit with documentation, and a bit asserted without toward the end:
 

in the US is considered to be 200-900 pg/ml. And in Japan the reference range is 500-1300 pg/ml, which means at 440, I too would be considered deficient.

Like the Natural News assertion linked earlier by Scott, This is an unreferenced and bogus claim.

The site you link is suspicious from the outset: it gives no reference for the claiim, just an assertion, and the site appears to possibly be a quack medicine operation.

A Google search of

Japan B12 reference range

... yields this site as the #1 hit [as of 2016/01/25], which is also kind of suspicious (the #1 most-linked source for info on the Japanese serum B12 reference range is a dodgy-looking Australian specialty website? Really?), and if you look down the search results you'll see an even more suspicious array of sites very insistent on telling you that your B12 levels are too low and citing the alleged Japanese reference range as evidence, almost all of them without citation or linking back you your linked site.

The pages I found that did make this claim or something similar and support it with a reference:

http://ijpbs.net/volume2/issue1/biological/_68.pdf
https://en.wikipedia.org/wiki/Vitamin_B12_deficiency
http://www.medicalcompassmd.com/b12-levels-us-standards-may-be/

... all point to this paper, whose 1988 publication date seems like it is consistent with being the source of the claim on the site you link that "Japan raised its B12 reference range to 500 – 1300 pg/mL in 1980s." However, this paper is neither an official publication of the Japanese Ministry of Health, Labour and Welfare (which issues the Japanese DRIs), nor of any medical or professional body, nor is it even single a functional or outcomes-based study of ordinary B12 deficiency: instead, it is a report of a disjuncture between serum and CSF B12 levels in patients with some kinds of dementia.

And what, exactly, is this paper even asserting about the reference range? If you then look at the actual wording in the abstract carefully, it says that "serum VB12 concentration in all the patients [in their study] was within normal limits, I.e. 500–1,300 pg/ml," which might be taken to mean that these are the normal limits (in Japan? In their patient population?), as your link asserts, but might also mean that serum B12 in the patients in their study ranged from 500–1,300 pg/mL, and that they were therefore all within normal limits — but that the actual limits of the reference range itself are (for instance) 200-1800 pg/mL. The full text is equally ambiguous: "Fig. 1 shows the results from the analyses of VB12 in the serum and cerebrospinal fluid. [Actually, no: it only has info on CSF levels -MR] It indicates a tendency toward CSFVB12 low levels, despite normal levels of VB12 in the serum (500-1,300 pg/ml)." And data in Tables 1 and 2 give presupplementation serum B12 values that in several cases exceed 1300 pg/mL, which is inconsistent with either interpretation.

Again, the site you link claims that "Japan raised its B12 reference range to 500 – 1300 pg/mL in 1980s." Well, this 2008 paper, from a group of Japanese laboratory medicine and analytical chemists, says that "Nowadays, sufficient dietary intake, i.e., dietary reference intakes, of vitamin B12 and folate are set in Canada, the United States and Japan based on the amount needed for the maintenance of hematological status and on the serum concentrations of these vitamins above lower reference values [refs] of 200 pg/mL for vitamin B12". For this fact, they cite:

Ministry of Health, Labour, and Welfare, Japan: Dietary reference intakes for Japanese, 2005 [Jpn]. 79-81, Daiichi-Shuppan, Japan, (2005)

Unfortunately, this citation is in Japanese; I can only find a summary document in English, and it has no info on serum reference ranges, just the DRIs and a brief summary of how they were derived. However, both it and the full English text of the Dietary Reference Intakes for Japanese 2010: Water-Soluble Vitamins say that the DRI RDA for adults in Japan is 2.4 µg/d, the same as in the US. It's hard to believe that they're assuming that the same intake is going to lead to serum levels that are at least twice the lower threshold considered adequate for Americans doing the same thing, even granted our greater average height and weight.

I'd say the claim of a 500 – 1300 pg/mL reference range in Japan is a case of a motivated website jumping on a misinterpretation of the the cited paper to make an agreeable claim.
 

Earlier I wrote:
 

[My GP] said that clinicians had high hopes a few years ago that homocysteine levels might be an independent predictor of cardiovascular disease risk, but it hasn't panned out, which I confirmed via a pubmed search I won't bore you with.

Well, it turns out that both my GP and I may have been wrong...

According to this new Cochrane meta-analysis [1] of the association between homocysteine (Hcy) and all-cause/CVD mortality posted today by Al Pater (thanks Al!), elevated homocysteine appears in fact to be a strong and independent predictor of both all-cause and cardiovascular mortality

 

Note that this is not actually a Cochrane meta-analysis, and does not adhere to their standards. It also is a usual greatest-to-least-group synthesis, rather than the preferred method of going back to individual patient-level data and then making a new analysis from the entire synthetic cohort. It also appears i a low-impact journal. And, one must remember that the role of Hcy in CVD is contested, and may be some kind of non-causal smoke rather than real fire. (I hasten to add that I lean pretty strongly toward taking it seriously — but not on the basis of this paper. Clinical trials of B vitamin supplementation to lower Hcy to prevent cardiovascular events have been ostensibly uniformly negative, tho' none have been well-designed to test the hypothesis by individually titrating vitamin doses to bring Hcy down to what are likely optimal ranges).
 

 

Cloud,

Despite risking sounding rude, let me repeat myself. See a doctor to get this taken care of ASAP. You should be getting way more B12 than you are to correct your deficiency. ...

Notice the dosage the Cochrane review investigated to correct B12 deficiency - 1 to 2 mg oral B12 per day. You 2.5 mcg per day converts to 0.0025 mg, which is 600 times less than the recommended dosage of 1-2mg to correct a serious deficiency!

Seriously. Get it fixed.

--Dean

Cloud,

I'll hop in and agree with the advice already given. Correcting B12 deficiency and ensuring maintenance often takes 500 mcg supplementation, which is what I've been taking for years to maintain a good mid-level B12 level. Irregardless of plasma B12, you should also be tested for methylmalonic acid (MMA) (and about the MMA test here) and possibly homocysteine as these require B12 to be metabolized, so elevated levels indicate ineffective B12 activity. This is most often the case with B12 deficiency, but some people need higher B12 levels to properly regulate these metabolic pathways.

 

Echoing all of this, with the clarification that while (as Dean says) crazy-high levels of B12 are often required to correct an existing deficiency (particularly in the elderly), one doesn't need anything like that as a maintenance dose once it's corrected, or for prevention of deficiency starting from a replete state.

[jfadden]

Old time mailing list member posting here for the first time.

Can anyone point me to a B12 supplement containing RDA levels (2.4mcg) or at most a bit more (say <10mcg).  All of the supplements I see are in the 1,000 mcg range or higher.  Those are appropriate for correction of deficiency but I am not deficient and just want a maintenance dose while avoiding problems I have experienced with very high doses.  There are multivitamin preparations with B12 RDA levels but I don't need all the other stuff.

 Thanks,
James

[Dean Pomerleau]

Hi James!

I bite about 1/6th of this 100mcg Solgars B12 supplement per day to get a small multiple of the RDA.

https://www.amazon.com/dp/B00014E9W0/ref=cm_sw_r_cp_taa_FwDCBbCW342NE

--Dean

[Saul]

 Dean!

My semi-annual bloodwork has always showed B12 to be in the standard range (my diet isn't vegan -- small amount of fish is eaten, most days.)

I'm 79 and in good health, continuing to practice CR.   My GP retired about 2 years ago; she recommended that I obtain a new GP specialized in gerontology.

Which I did. 

My gerontology specialized GP claims that seniors absorb B12 more poorly than younger people.  He claims,on the basis of my age, that I should be massively supplementing Vitamin B12.   As best as I can see, there is no known danger to overdosing B12 -- so that's what I've been doing, with the approval of my GP. 

  --  Saul

[Gordo]

Dr. Greger recommendations: https://nutritionfacts.org/2011/09/12/dr-gregers-2011-optimum-nutrition-recommendations/

 

Attention should also be paid to these nutrients:

Vitamin B12 (see also Which type of vitamin B12 is best)

• At least 2,500 mcg (µg) cyanocobalamin once each week, ideally as a chewable, sublingual, or liquid supplement taken on an empty stomach
  • or at least 250 mcg daily of supplemental cyanocobalamin (you needn’t worry about taking too much)
  • or servings of B12-fortified foods three times a day, each containing at least 25% U.S. “Daily Value” on its label
• Those over 65 years of age should take at least 1,000 mcg (µg) cyanocobalamin every day.
• Tip: If experiencing deficiency symptoms, the best test is a urine MMA (not serum B12 level)

Omega-3 Fatty Acids

• 250 mg daily of pollutant free (yeast- or algae-derived) long-chain omega-3’s (EPA/DHA)

Vitamin D (daily recommendations for those in the Northern Hemisphere; D3 from animal or plant sources may be preferable to the D2 sourced from fungi)

• Below approximately 30°latitude (south of Los Angeles/Dallas/Atlanta/Cairo)
  • 15-30 minutes of midday sun (15 for those with lighter skin; 30 for those with darker skin)
  • or 2,000 IU supplemental vitamin D
• Between 30° latitude (sample cities above) & 40°latitude (Portland/Chicago/Boston/Rome/Beijing)
  • From February through November
    • 15-30 minutes of midday sun (15 for those with lighter skin; 30 for those with darker skin)
    • or 2,000 IU supplemental vitamin D
  • From December through January
    • 2,000 IU supplemental vitamin D
• Between 40° latitude (sample cities above) & 50°latitude (Edmonton/London/Berlin/Moscow)
  • From March through October
    • 15-30 minutes of midday sun (15 for those with lighter skin; 30 for those with darker skin)
    • or 2,000 IU supplemental vitamin D
  • From November through February
    • 2,000 IU supplemental vitamin D
• Above approximately 50°latitude (north of Edmonton/London/Berlin/Moscow)
  • From April through September (or even briefer above 60°latitude (Anchorage/Stockholm))
    • 15-30 minutes of midday sun (15 for those with lighter skin; 30 for those with darker skin)
    • or 2,000 IU supplemental vitamin D
  • From October through March (or even longer above 60°latitude (Anchorage/Stockholm))
    • 2,000 IU supplemental vitamin D

Calcium

• At least 600 mg daily via calcium-rich plant foods—preferably low-oxalate dark green leafy vegetables, which includes all greens except spinach, chard, and beet greens (all very healthy foods, but not good calcium sources due to their oxalate content).

Iodine

• For those who don’t eat seaweed  or use iodized salt, a 150 mcg daily supplement
  • The sea vegetable hijiki (hiziki) should not be eaten due to high arsenic levels
  • Kelp should be avoided as it tends to have too much iodine

Iron

• All menstruating women should increase their absorption by combining foods rich in iron and vitamin C at meals and should get checked for iron-deficiency anemia every few years
• Men should be checked for an iron overload disease before any attempt to increase intake

Selenium

• Northern Europeans may need to take a supplement or eat a daily Brazil nut

-Michael Greger, M.D.

Edited August 14, 2018 by Gordo

[Sibiriak]

Quote

Saul:  As best as I can see, there is no known danger to overdosing B12

You may be right,  but there have been some mild concerns  raised about high B12 levels.

For example:

 

Eur Urol. 2016 Dec;70(6):941-951. doi: 10.1016/j.eururo.2016.03.029. Epub 2016 Apr 6.

Circulating Folate and Vitamin B₁₂ and Risk of Prostate Cancer: A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls.

Price AJ, et al.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094800/

Quote

The findings from this individual participant pooled analysis of 6875 cases and 8104 controls represent almost all of the existing observational data from cohort studies for the association of circulating concentrations of folate and vitamin B₁₂ with risk of PCa. Our results provide evidence of weak positive associations between circulating concentrations of both folate and vitamin B₁₂ and risk of PCa.

Quote

The modest 12% increased risk of PCa associated with a higher vitamin B₁₂ concentration is similar to that reported from a meta-analysis of five studies (fixed-effects pooled estimate per 100-pmol/l increment, OR: 1.10 [95% CI, 1.03–1.18]) [3], of which three studies were eligible for inclusion in the present analysis and contributed 45% of the data.

 

Edited August 14, 2018 by Sibiriak

[Sibiriak]

Selenium is another case where more may not always be better (along with iron, calcium etc):

 

Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults.

Bleys J¹, Navas-Acien A, Guallar E.

Arch Intern Med. 2008 Feb 25;168(4):404-10. doi: 10.1001/archinternmed.2007.74.

 

Quote

Conclusions:

In a representative sample of the US population, we found a nonlinear association between serum selenium levels and all-cause and cancer mortality. Increasing serum selenium levels were associated with decreased mortality up to 130 ng/mL. Our study, however, raises the concern that higher serum selenium levels may be associated with increased mortality.

 

Edited August 14, 2018 by Sibiriak

[Ron Put]

Association of Plasma Concentration of Vitamin B12 With All-Cause Mortality in the General Population in the Netherlands

Question  Are plasma concentrations of vitamin B₁₂ associated with risk of all-cause mortality among adults from the general population of the Netherlands?

Findings  In this population-based cohort study including 5571 adults, higher plasma concentrations of vitamin B₁₂ were associated with a 25% increased adjusted risk of all-cause mortality per 1-SD increase.

Meaning  These findings suggest that higher plasma concentrations of vitamin B₁₂ are associated with all-cause mortality, independent of traditional risk factors.

[Saul]

Hmmmm...

Correlation is not causation.  Higher levels of serum Vitamin B12 would be expected in meat eaters -- it seems possible that the higher mortality rate associated with elevated serum B12 may simply be due to the expected positive association between eating meat and higher serum B12.  Perhaps the correlation between higher serum B12 and mortality might simply reflect the positive correlation between meet eating and mortality. 

I scanned the article -- but not carefully.  It seems possible that the observed correlation might be yet more reasons to eat veggies rather than beef.

  --  Saul