Neural transmission requires substantial levels of Vitamin B12. By looking at everyday “annual physical” labwork, we quickly saw that Cheryl’s B12 was likely VERY suboptimal (in the mid 300s). That is, within reference range! But not nearly optimal. The drivers for her were unfortunately common: insufficient stomach acid (hypochlorhydria) and ongoing use of the diabetes drug metformin (notorious for depleting B12).
Cheryl started a trial of 1000mcg methylcobalamin twice daily, and within two weeks, she had no pain. Truly. Inspired, she started to reduce her own medication. And still no pain. Needless to say, Cheryl was indeed wildly-satisfied. She went on to accomplish many more aspects of wellness, but this was a perfect example of the power of Rapid Relief. She also referred a few of her friends to my practice.
With pain relief in hand – as well as Cheryl’s heightened enthusiasm – we could move on to the main reason she sought my help: reversing her type 2 diabetes. Some of you savvy practitioners have additional powerful tools to help with peripheral neuropathy (e.g. alpha lipoic acid); Cheryl eventually used this for a time too to help reverse her Type 2 diabetes, but taking full advantage of her immediate, available lab data helped to point to a true upstream root cause.
Be on the lookout for Vitamin B12 insufficiency (or even true clinical deficiency) in your clients. This is one of the most common opportunities I see in my clients, not a surprise when you realize several common categories of clients who frequently benefit from Vitamin B12 support. These include your clients who
1000mcg of methylcobalamin is a reasonable trial dose for your clients who wish to explore for 1-2 months for symptom relief from B12 support (e.g. Thorne, Pure Encapsulations, Jarrow). Note: there are some individuals who benefit most from a combination of the methyl form with the adenosyl form (due to suboptimal internal conversion), but for most, the methyl form is quite effective.
What benefits might your clients see from optimal levels of B12? Higher energy and physical stamina, improved memory and cognitive ability, relief from intermittent or chronic neuropathy (e.g. numbness or tingling in the extremities or other body parts), relief from cold hand/feet or cloudy thinking (from macrocytic anemia), relief from chronic cough (non-allergy-related), increased overall sense of well-being (from higher levels of serotonin), more consistent and deeper sleep (especially in seniors), relief from wheezing (especially in children with asthma).
Common lab markers. There are many more advanced markers to consider, but these two are typically run as part of an “annual physical” and can usually be covered by insurance and provided by almost any PCP upon patient request.
Organic acids testing allows you to get even more targeted by looking at functional Vitamin B12 sufficiency marker for a unique person. Learn more about methylmalonic acid here.
P.S. If you are passionate about transforming healthcare through the power of functional medicine, we encourage you to learn more about our training program here.
To receive clinical tips like this one right to your inbox, click here to receive our weekly newsletter.
Like us on Facebook to stay connected to our rich (free!) content and be notified of our popular, monthly Facebook Lives.
Cheryl’s story is a testament to the importance of B12 for healthcare professionals. Long hours, high-stress environments, and medication use can deplete our B12 levels. I’ve personally seen the benefits of B12 supplements in managing my energy levels and overall well-being. It’s a must for us in the medical field. I’ve recommended a B complex to my colleagues, and they’ve found it helpful.
I have a 63yo F client whose main complaint is lifelong fatigue. I was wondering if it is prudent to check MMA with a high serum B12 of 1709 (RR 200-1100) on 5000mcg methyl B12. This client’s MCV was suboptimally high at 96.1 (RR 80-100). Homocysteine was 9.5 (RR <10.4). I’m trying to narrow down why the MCV is sub-optimally high. She is not on any drugs that would cause low stomach acid, but she is hypothyroid and obviously her age is likely at play here.
We cannot address specific client questions in these public posts’ Q&A threads. As you know, many factors can play into the feeling of energy (or lack thereof), and you are considering one of them by looking at the MCV marker and thinking about all the factors that may be affecting that. Here are a couple of posts where we explore that topic in more detail:
https://schoolafm.com/ws_clinical_know/mcv-early-clue-to-brewing-disease-dynamics/
https://schoolafm.com/ws_qa/mcv-and-anemia/
https://schoolafm.com/ws_clinical_know/cert_pearls/
I have a patient currently taking a PPI and is extremely reluctant to get off of it. We are working on eating hygiene and then we will start a VERY SLOW wean. While he is taking the PPI is it safe to supplement with HCL w/ betaine to help increase digestion? His B12 was 557 and he is hesitant to taking many supplements, so I am just trying to see if we could add in the HCL to increase his B12 levels versus a supplement at this time. Thanks!
You may find this post on the root causes of acid reflux interesting:
https://schoolafm.com/ws_clinical_know/acid-reflux-truths-and-myths/
Typically, you would first work on the root causes that create the need for the PPI in the first place, and then you would start the PPI wean-off process alongside the prescribing physician. Depending on how long the patient has been on the PPI, one may want to support the protective stomach lining with mucilaginous herbs before introducing any HCl supplements, to minimize any adverse effects. In the case that you are describing it may be more beneficial to go with sublingual B12 in a lozenge or liquid form to bypass the typical GI tract absorption. This study may also be of interest to you: https://pubmed.ncbi.nlm.nih.gov/29499976/
What about someone with consistently low B12 levels and a high normal homocysteine (normal MMA), who is symptomatic with fatigue and brain fog? She has tried to supplement b12 even at tiny doses, but she develops what seems to be neuroinflammation with cognitive/recall deficits that can persist for weeks even after dosing is discontinued. We have tried methyl and hydroxycobalamin both with the same effect. I’ve wondered about the possibility of a cobalt allergy? Or is there a detox process that might be sluggish in some downstream process causing a buildup of toxic mediators? Interestingly, this patient also gets severe, hangover-type headaches with even small doses of CNS affecting mg (like glycinate). Maybe this is a related issue? I can’t seem to find any other reports of this kind of apparent toxicity from even a few micrograms of b12. Thanks for any help!
This is a beautiful example of bio-individuality and that reference ranges are for the majority of people and are not always indicative of health/disease. You may be interested in this article that is relatively recent: https://pubmed.ncbi.nlm.nih.gov/31193945/ And your hunch about the cobalamin allergy may also be on the right track as there are a few reports of such cases in the literature. The toxicity may be at play as well. What truly stands out is the possibility of existing oxidative stress that gets exacerbated with the B12 addition. Thus, what else is missing for this person? What else is potentially causing oxidative stress? Is it their diet? Stress? Overexercise? Toxic burden, or imbalance in phases 1 and 2? I would encourage you to think in broader terms and ask more puzzle-piecing questions instead of trying to go after the correction of one consistently low value. Think about what is upstream of that symptom. Why this may be the case for this individual – is it consumption? is it an issue with absorption or delivery to the cells? What else is at play? Using the functional medicine approach and investigating the full picture of symptoms and health history may help you… Read more »
Can methylated B12 be harmful if a person has mercury toxicity? I read that methylcobalamin binds to mercury and we get a more toxic Mercury in the body?
B12 is a key nutrient necessary to remove mercury from the body in the process of heavy metal detoxification. It can be harmful only if added too fast and/or when the detoxification pathways are not open or balanced, which could lead to oxidative stress overwhelm the system. There is an entire deep dive clinical course inside of SAFM devoted to this topic.
Yes, B12 has a high affinity to mercury and can bind this heavy metal when provided from food or in a supplement. These references may be of interest in this vein:
https://www.researchgate.net/publication/240860126_The_Link_Between_Vitamin_B12_and_Methylmercury
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC202093/
Hi Tracy, I was wondering if you had any recommendations for a pregnant patient with PCOS who is weaning off Metformin and wants to support her B12 status. What dosage of B12 would you recommend during pregnancy in this case?
Indeed, Metformin can lead to B12 depletion over time, but this does not always mean that everyone who takes this drug is B12-deficient. As a savvy practitioner, it is best to stay away from this type of black and white thinking. Therefore, it would be best to asses the B12 status of your client/patient by checking the serum B12 and the methylmalonic acid (MMA) status first and then decide if the supplementation is needed and what dose. This study will give you a better idea of what range to recommend:
https://bmjopen.bmj.com/content/7/8/e016434
A patient who has been taking methylated B12 for the last 2 months had her plasma B12 level checked and they came back recently >2000. It is way too above the reference level of 800. Her only complaints are a headache and low energy. Do you suggest stopping the methylated B12 since it is not getting to her cells? She did say her energy level is up when she is on Methylated B12, but the level is concerning. I appreciate your input. Thank you
It is indeed not uncommon to have higher than normal serum levels of B12 while on a supplement – all this means is that the supplement is well digested and absorbed into the bloodstream. It is not indicative of B12 not being absorbed into the cells – to check that one would need to look at more functional, B12-dependent cellular markers such as methylmalonic acid (MMA), MCV in the CBC panel and homocysteine.
I have a 72 year old client that is a vegetarian with neuropathy, but her MCV is 86. I know that the MCV based on both folate and B12, but can someone still be b12 deficient with an optimal MCV? Any help would be appreciated! Thanks!
Yes, one can still have insufficient B12 even if their MCV looks optimal. MCV is a marker that depends on B12, folate, and iron and, especially when it is in the lower half of the reference range, it is possible that other nutrients are ‘making up’ for suboptimal B12 status. Given your client’s age and existing neuropathy, it would be appropriate to check more functional markers such as the homocysteine levels as well as the methylmalonic acid (MMA) to better asses the B12 status. Also, making sure that blood sugar regulation is in a healthy range is of top prority. High blood sugar and elevated levels of oxidative stress can be damaging to the nervous system, and other systems as well (eyes, kidneys, etc.). This may be of interest to you:
https://ashpublications.org/blood/article/106/11/3709/122255/Iron-Deficiency-and-Vitamin-B12-Folate-Levels-A
https://www.ncbi.nlm.nih.gov/pubmed/31490017
One needs to be also sensitive to your client’s choice of eating a vegetarian diet, as those tend to be low in B12:
https://www.ncbi.nlm.nih.gov/pubmed/30828450
Would you recommend the Adenylsyl/Hydroxy version of B12 for someone who likely has a problem with intrinsic factor over the methycobalamin type? I have a client who may have a serious deficiency, and I want to be able to make sure she is going to be able to utilize it as efficiently as possible as she does not want to take the shots.
I appreciate your thorough thinking about how to ensure a nutrient put in the mouth actually gets to the cells that need it! But my answer might surprise you: methylcobalamin does not require intrinsic factor for absorption. We need ample stomach acid (and the intrinsic factor it triggers our parietal cells to secrete) in order to isolate and bind food-bound cobalamin for absorption down in the intestines. Methylcobalamin does not require modification for absorption. There are some people, however, who find they benefit most from supplementation with a combination of B12 forms because they don’t well convert internal to the body, but for most, the methyl form is well absorbed and utilized. For a deeper understanding of B12, I highly recommend you review this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875920/. Dr. Ben Lynch offers a great, simple lay write-up that is easy to share with patients and clients: https://www.drbenlynch.com/resource/b12-supplementation-need-methylcobalamin-adenosylcobalamin/ . Enjoy!
Hi Tracy,
What about these super high mega shots of B12 … on the order of 5o,ooo “units” (Mg or Mcg?) that I hear some doctors doing.
I’m not sure, but don’t believe the body stores much B-12, so it seems to me that that a 1-time mega dose … esp. that high … to counter low CBC panel B12 number … may not be that effective at all, much of it being wasted.
Thanks!
Tom
Generally, the safety profile of B12 is quite high; there are no known risks of high-dose supplementation and no studies demonstrating otherwise,to my knowledge. However, I am generally not a fan of sudden, massive doses of any nutrient (excepting of course immediate, life-threatening concerns e.g. magnesium on the stat cart in the ER, and extreme-dose B12 has been shown to prolong survival in advanced ALS patients e.g. http://n.neurology.org/content/84/14_Supplement/P7.060). Generally, I believe in ramping up gradually and allowing the body time to adjust – both in terms of receptor number/sensitivity for nutrients as well as biochemical processes that might have been flagging beforehand due to suboptimal nutrition. For B vitamins, we need to remember that detoxification requires them, and a sudden glut of nutrients can promote a wave of processing that might overwhelm or even do harm in the short-term. For B12 in particular, we know it’s critical for methylation, and we have all seen what happens when an individual over-promotes detoxification pathways too quickly and becomes overwhelmed with “detox symptoms” (e.g. acne or other breakout, nausea, anxiety, dizziness, heart palpitation, diarrhea, joint pain, stiff muscles). Of course, if injection is of the cyanocobalamin form (vs. hydroxocobalamin), the amount of cyanide… Read more »
Tks Tracy! Great perspectives here. Another Q 4 U Re: B12 or any other nutritional supplement (aside from low stomach acid or gut impairment that could cause nutritional malabsorption, etc. of a supplement), what’s your take on a supplement’s “biological availability”, overall potency, potential usefulness within the body? From what I’ve read, poor quality supplements can contain lower grade ingredients (e.g. cyanocobalamin vs. hydroxycobalamin), lower grade forms, use of many fillers in low grade supplement, or perhaps a coating on the pill that impairs breakdown (and thus absorption in the gut, etc.) The assumption is thus that all things being (relatively) equal, a higher-quality designed supplement might or will be more biologically available to the body than a lower/poor grade … and thus have a larger impact. Related to this, are you aware of any testing labs/services that test supplements for bio-availability levels allowing for some form of comparison between different supplement vendors? Thanks!
Oh indeed, I agree 100%. This is a fun question. We are going to talk about many variations and examples of the point your question is raising within the Nutrients/Supplements 101 course coming up in your Semester. The challenge is that people in aggregate will have varying levels of sensitivity to the distinctions you raise. A person with impaired digestive secretion, for example, may have more trouble breaking down tablets (vs. capsules). A person with damage to the mucosal lining of the intestines (e.g. from strong dysbiosis) may have particular trouble absorbing iron. A person with no gallbladder may struggle in particular with digestion (and thus absorption) of fat-soluble vitamins taken orally; perhaps sublingual will be a better choice for them. In the same vein, we could expand the discussion to the choice of getting nutrients from food vs. supplements depending on an individual’s ability to find, afford, prepare, palate, digest, and absorb well (without immune rejection) specific foods. We are such crazily *unique* organisms. But I digress… Some of the concepts you raise re: cyanocobalamin vs. methylcobalamin or Vitamin D2 vs. D3 or zinc picolinate vs. citrate et al. have been demonstrated in clinical studies (e.g. https://www.ncbi.nlm.nih.gov/pubmed/3630857). Others are… Read more »
Hi Tracy,
I have a newly pregnant client with very low B12 (225), she is also low in zinc and magnesium which suggests low stomach acid. I talked with her about taking some apple cider vinegar mid-way in a meal but she found that unrealistic for her lifestyle. Is taking Betaine HCL with pepsin appropriate during pregnancy? Are there any additional strategies to try?
Thank you,
Abby
Indeed, it’s especially important for a woman to optimize her digestion during pregnancy in order to ensure adequate nutrition for her and the fetus. For sure, I would fully explore “Eating Hygiene” concepts with her first, especially drinking too much liquid with her meals or using meal time as the primary opportunity to hydrate during the day. However, using HCl betaine is indeed appropriate if there is insufficient stomach acid. If this woman has an omnivore diet that includes daily animal protein, then I agree 100% that the very low B12 is justification for exploring stomach acid support. Just keep in mind that as a woman’s womb expands, it’s common for there to be some GI symptoms including acid reflux, simply due to crowding of organs and glands. Her needs may be less later on. Also, keep in mind that low stomach acid is often caused in party by hypothyroid function. As the fetus’ thyroid hormones “come on board” and benefit the mother, her digestive secretions (and motility) may improve substantially. This starts early in the 2nd trimester and gradually increases over several weeks; something to keep an eye on over time.
(There is a typo in you article in the B12 units). I am type 2 diabetic, 20 years, on 2500 grams of metformin daily, no insulin. I am now on a low carb/high veg/moderate protein diet and want to reduce(eventually eliminate) metformin. I just ordered Berberine and had a question about B-12 supplementation. Do you think I am low in B-12? My doctor said according to the labs I am normal. Hmmm… I do have tingling in extremities, sometimes more often than others. I am 60. Thank you!! My VITAMIN B12 was 562 pg/mL.
Thank you for catching the typo; we have fixed it above. Obviously I cannot advise you on your unique situation in this arms-length forum. What I will offer is the difference in the perspective of what is “normal” (meaning within the reference range – that is the statistical “norm:’- which simply captures what 95% of the populations has) vs. what is optimal (meaning plentiful to allow your unique body to thrive). The word “Normal” wrt lab values does not mean optimal or even healthy or sufficient. We have unique needs for nutrients based on our genetics, our history, and our current lifestyle. Some people may thrive at 562 while others are insufficient and find they benefit from Vitamin B12 supplementation (e.g. methylcobalamin). Even moderately elevated blood sugar over time also does damage to nerves which directly contributes to diabetic neuropathy which would increase the nerves’ requirements for B vitamins and for antioxidant support.
Hi Tracy, First off, I am so grateful to have found this website and all of the incredible information you have put together. Thank you!! I have a female client who is 32 years old with suboptimal B12 (530) , low ferritin (20), low total D (38) and is taking metformin (prescribed for her PCOS, but she has not had any symptoms since having her first child a year ago) and wellbutrin who experiences headaches daily. She is relatively healthy and feels ok day to day except for the headaches. She is exploring the possibility that the headaches are related to jaw clenching and is trying out acupuncture and some other therapies related that she is hoping will help. She is working on eating more vegetables as well as buying better quality animal products and lowering her intake of processed foods and sugar (big sweet tooth). I read in a previous thread that low b12 and ferritin can both be a sign of low stomach acid. Do you think a good course of action would be to have her try to start taking betaine HCl/pepsin along with continuing to work on improving her diet? Or would you suggest supplementation with… Read more »
You are so very welcome! Assuming your client eats a generally carnivorous diet (esp. if it includes some red meat), then I too am suspicious of suboptimal digestion and/or perhaps nutrient absorption. However, there are also some other logical, possible explanations I encourage you to consider for a moment… Use of metformin depletes B12, so that may be the most powerful root cause for that nutrient? Insulin resistance (which she may still have given her prior history – check HbA1c (want <5.3%) and fasting insulin (want bottom 1/3 of reference range!)) depletes magnesium. Heavy menstrual cycles can outpace serum iron and, in some cases, ferritin as well (especially if the latest data was collected immediately following a menstrual bleeding cycle - always ask about timing!). Unless she is using oral Vitamin D supplementation, her D status may be simply a reflection of the time of year and her home location. If possible, I would try to acquire both RBC Zinc and RBC Magnesium bloodwork; two more nutrients that require ample stomach acid and nutrient absorption. I find that suboptimal magnesium is *very* often a root cause of chronic headache. The one marker you didn't mention that will likely give you… Read more »
Have you heard of sublingual perque activated b12? http://www.perque.com/product_sheets/PERQUE-Activated-B-12-Guard.pdf?
Thoughts? And do you think that is good for daily use?
I don’t have any experience with this particular formula, but certainly there are many other B12 lozenges available that are designed to maximize sublingual absorption where suboptimal digestion/absorption might minimize B12 via food. This particular formula is using the hydroxy form, while others use the methyl form (e.g. Jarrow methyl B12 lozenges). Both are activated forms used directly in biochemical processes; the body should ideally well convert between the methyl, adenosyl, and hydroxo forms as needed. Of course, we have can SNPs with larger or lower levels of various enzymes. Some initial (it’s early days yet) research shows that those with COMT SNPs might do better with (or adenosyl forms of B12 (vs. methyl). But of course, each person is unique, and many factors are coming together at once in determining what is needed. Because it’s much less expensive and easy to find, I typically use methyl-B12 for a client who needs separate B12, but in a handful of cases (small percentage), they need another alternative. This may be of interest to you: https://seekinghealth.org/resource/4-forms-of-vitamin-b12/. (Of course, there’s a deeper dive on the whole subject of methyl-B12 being a methyl donor. Some people need more of these; others are already overloaded… Read more »
If you are doing B12 injections I assume this means we do not have to worry about doing with food…Am I missing something?
Hi Tracy,
What do you think about the B12 injections? Is 1000 mcg weekly sufficient for someone with B12 insufficiency?
Certainly, injections can be a way for someone to return to sufficiency rapidly. And yes, 1000mcg is the typical dose delivered in this way. It’s also a particularly important solution for those who may have autoimmune pernicious anemia (so not able to use intrinsic factor to allow intestinal absorption) or those who must be on long-time acid-suppressing medications due to chronic concerns e.g. Barrett’s Esophagus.
Is the dosage for someone with suboptimal B12 1000mcg daily? The Jarrow B-Right says 1 pill daily with 100 mcg of B12 included. That would mean 10 pills daily.
It depends on the spectrum of need. A clinically low Vitamin B12 (<250 pg/ml) likely needs even higher intake e.g. 1000mcg twice daily. I would use the 1000mcg dose once daily for someone who has low B12 (~250 to 500). These are individual targeted B12 doses in an individual supplement. The B-Right you mention is a B-complex with only small amounts of B12 which is intended to ensure day-over-day sufficiency of all B vitamins at once - which would be appropriate just for maintenance of healthy levels for someone with high stress, erratic eating, hypothyroid, poor eating hygiene or other factors that might cause sufficiency to be intermittent. Various B complex supplements feature different levels of the different Bs, so you can choose one based on what you most need to support (e.g. Thorne’s B-Complex #12 has a higher level of B12). In some cases, a client may need to use a separate B12 as well as a B Complex – depending on what needs to be addressed. Obviously our intention over time would be to remedy the dietary or digestive or toxicity issues at play in keeping the levels low, so that eventually a separate B12 is not required.… Read more »
Hello Tracy,
Thank you very much for expertise.
This patient is over 60 and about 10 years ago had stomach ulcer surgery.She does her best to eat healthy.
Thank you very much for expertise.
Hello Tracy,
i have a client who achieved 936 blood level of B12. What is the next step? Should they decrease the dose or take a break?
I aapreciate you for giving me your expertise.
Regina
Hi Regina – thanks for your question! Generally, I think a serum B12 of 936 is likely quite optimal and not a concern when it has been achieved and upped via supplementation. As we have discussed, the typical “normal” range is simply what ~95% of the population has. In other countries where references ranges are target ranges, the upper end goes much higher ~1300 pg/ml. There are no known risks of having B12 be in this range due to supplementation. Ultimately, however, you want to check cellular markers to see if there is cellular sufficiency. I recommend both MCV (part of a Complete Blood Count) and MMA (methylmalonic acid). You want both to be in the lower half of the respective reference ranges. MCV is affected by both B12 and Folate, while MMA is more specifically affected just by B12. Let the cellular markers tell you whether the ongoing supplementation dose is optimal or should be increased.
Thanks a lot Tracy for reply. I’ll check if my client has these once on their labs. In general, what do you do when optimal level was reached?
Typically with B12 in particular, I recommend my clients continuing using it to maintain that level – unless/until we are confident we’ve addressed the root cause of the level being too low (e.g. inadequate animal protein intake, low stomach acid, poor eating hygiene, dysbiosis, hypothyroid, etc.). In some cases with older clients (esp. age 60 or older), it may be that suboptimal stomach acid is an ongoing challenge that simply cannot be remedied without some form of supplementation due to age (e.g. the B12 or supplemental HCl betaine – or both).
A client who has neuropathy post chemotherapy: is this neuropathy related to B12 deficiency or is a toxic side effect of the chemo from damaging good cells?
Actually either, but I believe most likely both. Cellular damage might impair stomach acid secretion (exacerbated by low adrenal function – a common outcome of chemotherapy) which could impair B12 absorption and/or damage to the intestinal liming tissue which would also impair absorption. I would support with a high-B12 complex (e.g. Thorne’s B-complex #12) as well as mitochondrial support (I always do this for my clients post-chemotherapy) including twice-daily CoQ10, L-carnitine, and R-lipoic acid (the Cellular Metabolism course includes great detail on these elements). You might also assess whether supplemental “HCl with Pepsin” is warranted for optimal B12 absorption (look at Albumin: is it suboptimal? What about RBC zinc, assuming a carnivorous diet; is it in the upper half of TRR?).