010: Functional Blood Chemistry Sneak Peek: Understanding Vitamin B12, MMA and Folate





Welcome to The Clinical Entrepreneur, a business podcast that’s dedicated to healthcare practitioners just like you who are hustling every day to build a business and a life you’re proud of. Join me, Ronda Nelson, as I share my own experiences and extract actionable advice from industry experts about what it takes to build and scale a profitable wellness practice.




Well, hello my friend. Welcome back to The Clinical Entrepreneur Podcast. I am your host, Dr. Ronda Nelson and I am so glad that you are with me today. As you can see, this is a sneak peek at our understanding of the Blood Chemistry Seminar that we’re getting ready to dive into. We’re right in the middle of the registration for that, which is open from September 14th – September 16th. So you may not have a lot of time left to get registered, but I thought I would share a short clip about how I will be talking about vitamin B12, methylmalonic acid, and folate, and as it has to do with understanding how to use blood labs with your patients. I will also be discussing how to understand labs in a way that you can easily explain to your patients, help them understand, and give you the tools that you need to be able to make recommendations for diet, lifestyle, nutrition, etc. So, let’s dive right in.


First, let’s talk now about the three markers that have to do with Vitamin B12. Many times, just B12 is tested and there are two other markers that we need to look at in context, that are also taken together. We need to look at all of them together. That’s B12, Serum B12, MMA or Methylmalonic Acid, and then the third one is Folate. To start, we’re going to discuss B12.


Let’s begin with a little bit of background. Of course, this is how we always start. The majority of Vitamin B12 comes from animal sources. So we automatically know that if we have a patient who is a vegetarian or vegan and they’re not eating a lot of animal proteins, animal products, then there’s a high likelihood that they’re going to be low on that B12 deficiency scale. Now, many people believe that you can get the same kind of B12 from oral ingestion, i.e. taking some kind of supplementation or using foods to get that B12, but that is a secondary solution. The body prefers and utilizes B12 much better and more efficiently from animal products. When we eat these foods that have B12, there is a protein that’s released in the stomach called intrinsic factor, and we kind of need two things. We need hydrochloric acid, a sufficient amount, which is problem number one. And then the second thing we need is an intrinsic factor that is released from the parietal cells.


So, when B12 comes in, it’s all tied up in a food matrix and the HCl or Hydrochloric Acid breaks that B12 apart from its food carrier. It then requires intrinsic factor to be absorbed further down the digestive tract in the ileum. Once it’s absorbed, we have a protein called Transcobalamin and that protein is what transports it in the bloodstream. So, when B12 gets unhooked by HCl in the stomach, it doesn’t hook to intrinsic factor right there. We often think that it does, but it doesn’t hook back to intrinsic factor in the stomach. It moves along in the digestive tract through the duodenum and the jejunum along with intrinsic factor. They kind of travel together. Once the B12 gets down to the ileum along with intrinsic factor, they hook together and that intrinsic factor is what allows the B12 to be absorbed. Now, patients with SIBO or other digestive issues where we’ve got bacterial overgrowth that might be up in that ileum can break, it can consume the B12 before it gets to where it needs to with intrinsic factor leaving the patient with a relative B12 deficiency.


We want to make sure that we’ve dealt with digestive issues. We’ll talk about that in a minute. We’ve dealt with digestive issues, but most importantly, the source of B12 needs to be animal. Secondly, we want to make sure that there’s enough hydrochloric acid in the stomach, i.e., we’ve got enough of the cofactors and minerals. We’ve got enough zinc. We’ve reduced stress response because when that sympathetic state is all fired up, they’re not going to produce the sufficient gastric juices to be able to break down food. Then, we want to make sure those parietal cells are working. Now, most of the B12 is stored in the liver and we store a significant amount because B12 is very important in the body. So, it’s very, very efficient at conserving it. It stores about a three-year supply in the liver. Therefore, when you see a B12 deficiency on a blood test, that deficiency has been ongoing for some time. It didn’t just show up today. It means B12 storage in the liver has been depleted for quite some time.


Since B12 is such an important vitamin, and we need it for so many different things, very little B12 gets excreted. However, if we take too much in, i.e, the patient is taking a little bit in this supplement and a little bit in this one, and a little bit more over here, and then we look at a blood test and see high levels, one of the things we want to rule out is if the patient is possibly getting it from multiple places. And so, all added up together, they’re being overdosed on B12. We need B12 to help us carry oxygen. It helps carry oxygen in red blood cells. It’s needed for carbohydrate metabolism. It’s important to maintain nerve function and keep those nerve cells healthy. It’s part of the myelin sheath and it helps make the DNA inside our cells. So, B12 is absolutely essential. When there’s a deficiency, for some patients it can actually result in what’s called Megaloblastic Anemia and that is a Macrocytic Anemia, where the red blood cells are larger than normal, they’re immature, and that will reduce the amount of oxygen that gets carried by the blood to the body tissues. It then ends up being a folate/B12 deficiency.


We know that B12 is very important and one more thing we have to remember is that B12 is needed for that conversion of homocysteine into methionine, and homocysteine is a bad guy. We do not want homocysteine building up. We need to keep that process moving, keep that conversion moving so we can get that homocysteine broken down into methionine, and that’s where B12 is essential. Often vegetarian or vegan patients can have higher levels of homocysteine just because they don’t have adequate amounts of B12. We’ll sometimes see long-term neurological complications, and the sad part is that many times those cannot be reversed with a chronic B12 deficiency. It could be a lack of intrinsic factor or it could be that there’s not enough intrinsic factor from the parietal cell to be able to absorb the B12 in the ileum. Sometimes you can assume or suspect, as part of you ruling out what might be going on with a deficiency, you could look at the patient that comes in with progressive peripheral neuropathy. What’s happening? The neuropathy is getting worse and worse, you might think B12.


Anemia that is unresolved. In other words, you can get on top of it. You’re doing everything you can and the anemia picture is not changing. Another key sign can be a swollen tongue or a red tongue. So you can think of anemia or B12 deficiency as a possibility there. Healthy adults need about 2.5 micrograms of B12 per day. The average dose of a B12 over-the-counter is 1,000 to 2,000. So, it’s way higher than what we really need. We don’t need to over supplement with B12. Because what happens is when the patient doesn’t have enough intrinsic factor, they don’t have enough hydrochloric acid, and the only way to “force a result” is to dose them high with B12 and hope that they may be absorbed a little bit of it. That is not going to be a great idea because we’re going to end up with overdosing or high levels of B12.


Like I previously mentioned, deficiency can be progressive. When you see it, it’s been going on for quite a while. A mild deficiency will be on a blood test, just serum B12. You’ll see it between about 350 and 450 as starting to be deficient. If it’s between like 200 and 350-ish, then it’s a moderate deficiency. But when you see a B12 that’s below 200, there is a severe deficiency and very often you’ll see neurological symptoms, severe memory loss, could be incontinence, loss of taste and smell, paranoia, some mental anxiety, depression, that kind of thing. We never, ever want to see them below 200. But it’s easy when we’re looking at it from a bigger perspective to say, “Well, if we’ve got a B12 level that’s around 400, we might have a little bit of a deficiency that’s starting to occur and then we can catch it ahead of time, which is great.” So, now when B12 gets elevated, high levels aren’t a reason to panic, it can be because of a number of different things. We always want to look at the underlying cause. Now, there could be a severe condition involved or it could be just as simple as the patient is taking too much. They’re getting too much in their diet or their supplement.


Some of the things that can contribute to elevated B12, because they dis-regulate the ability of the body to absorb B12, could be malabsorption. Not enough or poor absorption, along the intestinal tract. It could be an increase of transcobalamin or other transport molecules in the bloodstream. O it could be alcoholism. Those can all cause an elevation of B12. We could even just have a loss of intrinsic factor, as I mentioned, that goes along with malabsorption. So we’re getting it, getting it, but we’re not absorbing it. We could just be getting a lot of high dose of B12, without realizing that the body is actually not able to use it. And then there can be more severe diseases, such as diseases of the liver, kidneys, and blood like leukemia. They can also be associated with higher levels of B12. So, if you’re worried, you want to rule out things like hepatitis. You might want to rule out cirrhosis. So, look at those liver enzymes on a blood test. It could be alcoholic liver disease.


So we’ve got a deficiency of Transcobalamin 2 but an overproduction of Transcobalamin 1 and 2. I’m not going to get into that but those are the transport proteins. It could be kidney failure or it could be just excess accumulation in the blood, but remember, we don’t excrete a lot of it. So this would be a long-term type of disease state. Then SIBO, as I mentioned, can be a big, big problem for elevations in B12, as well as a deficiency in B12. What happens with SIBO is sometimes the bacteria can produce an excess number of the B12 analogs. The bacteria is driving the elevation, but SIBO specifically can cause a decreased B12 sometimes. Then there are some cancers or tumors that have been associated with elevated B12 and when I say elevated, these are levels up over 1,000. So could be a liver carcinoma or secondary liver tumors. It could be breast cancer, bowel, stomach, pancreatic cancer. You’ll see those with elevated production of transcobalamin.


Now let’s talk about how we can best get this from food. Our food sources are going to be liver, sardines, salmon, tuna, beef, eggs, raw milk, etc. The best sources are going to be animal products. If you do have to take supplements with B12, which I don’t recommend, how about we just fix the problem, if it’s a deficiency? Let’s get them eating the food that is going to contain B12, make sure we have enough hydrochloric acid, and enough intrinsic factor to be able to break B12 out of its food matrix. Then intrinsic factor travels through the GI tract down to the ileum and shuttles that B12 across the barrier into the bloodstream. The things you want to watch for are poor dietary intake with a decreased B12. It could be malabsorption. It could be hypochlorhydria. It could be SIBO. Sometimes a pancreatic insufficiency could be there. Even patients that have had gastric bypass, which makes sense because we’ve lost the ability to break down the B12 because of the loss of parietal cells from the gastric bypass. Then if it’s increased, think about possible inadequate uptake into the tissue. It’s moving around in the bloodstream but it’s not being taken up into the tissue. It could be cancer. It could be diabetes. It could be a severe liver disease. You’ll have to kind of rule that out based on what you’re seeing in that particular patient.


Now, let’s look for a minute at Methylmalonic Acid or MMA. This is a byproduct of the metabolism of fatty acids and amino acids. That’s one thing, but here’s the key, MMA requires B12 to work. Therefore, when there’s not enough B12, we will see discrepancies in MMA. When MMA, Methylmalonic Acid, is increased, you’ll have a B12 deficiency. So, that’s what we want to look at, when MMA it’s increased, we know that we have a B12 deficiency because MMA needs B12. It can’t break down the fatty acids and amino acids without B12. If we see a high MMA, we automatically know that we’ve got a B12 deficiency. The lab range for MMA is going to basically say 0 to about 325 or so. We want to have it at about 0 to 260. No higher than 260 is optimal. If MMA is above 260, you can start to suspect a possible B12 deficiency.


In addition to B12, you might also think about maybe parietal cells not working in the stomach. In that case, you might want to consider using digestive bitters or bitter herbs to try and upregulate and improve the parietal cell function. You could have impaired absorption of B12 along the GI lining somewhere. Also, sometimes MMA will go high if there’s kidney insufficiency so we might see that there as well. So, methylmalonic acid, I think it’s probably a better indicator than serum B12. If you’re wanting to look for the amount of B12 available at the cell level, MMA is probably a much better marker.


Now, let’s look at folate and we’re just going to touch it. We could take each of these three subjects and we could do two, three, four hours on each one of them. That’s not what we’re doing here. But folate, let’s talk about that. That’s also known as B9 and it’s a coenzyme that’s needed in part of the methylation process. It’s found in whole foods like liver and organ meats. It’s also found on egg yolks. There’s a pretty good amount in black-eyed peas and beets, although that’s not a staple of the American diet. B12 is needed in order to incorporate fully into the cells. So, B12 and folate often go together and that’s why MMA is an important marker because it distinguishes between B12 and a folate deficiency. So, when we look at B12 and folate, MMA has to be in that range. Our target range for a really, really spot-on perfect level of folate is going to be 15 to 25. That’s about where we want it to be.


Folate’s needed during the nervous system development especially during that first trimester of pregnancy. It converts histidine into glutamine. It’s absorbed in the small intestine and stored in the liver just like B12, and often you can suspect a folate deficiency. There’s pretty good research on this when you have a patient that has restless leg syndrome. Even cervical dysplasia has been associated with a folate deficiency. And as you can imagine, because folate, just like B12 has to be absorbed, if we have malabsorption or some kind of inflammation along the GI tract, we could likely have a folate discrepancy or deficiency. So, we always want to look at folate as it has to do in food or how we can get it in food. B12 is largely from animal products, but the great news is that folate can be found easily in other foods. So, yes, organ meats, liver, and egg yolks. However, there’s a great amount of folate in avocado, so I tell my pregnant mamas to make sure they eat guacamole every day. Also, there’s a pretty good amount in asparagus, cauliflower, broccoli, brussel sprouts, and even beets have a good amount of folate in them.


We can use dark leafy greens as well as okra. There are a number of significant foods that we can use that will really make a difference and get this folate in the body to help work together in tandem with B12. When you’re thinking about a folate or a B12 folate deficiency, we want to look at serum B12. That will often be decreased and you’ll see folate will be increased. That’s a B12 or folate deficiency pattern. We’ll see low B12, higher levels of folate, and often you’ll see a lot of the red blood cell markers like MCV, MCH, MCHC. Those will be elevated, but the red blood cells, hemoglobin, and hematocrit are often decreased.


So you’ve got the charts. They’re all ready for you. You’ve got them in your notebook and in the Quick Start Guide as well. All of these are all sitting in there together, so don’t panic if you can’t take notes fast enough. I got you covered. No problem.


To finish up this section, let’s look at when folate is increased, what that can indicate. If folate is increased and is outside of 25, 30-ish, we have either folate and/or B12 anemia, and that’s where MMA comes in as being helpful because we can distinguish between the two. It could be that there’s just a dietary insufficiency, i.e., the patient is eating a lot of refined carbohydrate-type foods and they’re not getting enough guacamole, red bell peppers, beans, nuts, seeds, broccoli, cauliflower, all those foods. We want to make sure that we’ve got enough folate for our pregnant mamas. Sometimes you can see an increase in folate during pregnancy and that’s normal if that happens. There are a couple of medications that can cause an increase in folate and that would be anti-seizure medications. Methotrexate can sometimes cause an elevation in folate, as can alcoholism. So, a person who’s got some alcoholic tendencies can also have issues with higher levels of folate.


Then there are a few medications and I didn’t previously mention these, but there are a few interactions that can cause a B12 deficiency medication-wise. I didn’t touch on these yet, but it’s so important. One of them is a certain type of antibiotic that’s used to treat certain infections and it’s not a very common one called chloromycetin. That’s an antibiotic that can inhibit the body’s absorption of B12. PPIs like omeprazole, Prilosec, Prevacid, that kind of thing. So, PPIs and H2 blockers are going to block B12 because they are hitting at that site of absorption. There’s not enough acid in the stomach and they’re blocking the acid, whether it’s at the H2 receptor or at the proton pump level. They’re blocking the production of acids and then we’re not going to have enough B12. Then metformin is also a drug that can interact and cause decreased absorption of vitamin B12.




So, that is the section on vitamin B12, methylmalonic acid, and folate and how the three of them work together for you to be able to get a better picture of what’s happening with your patient. What do you think about that? That’s a pretty nice little dive into B12, MMA, and folic acid. I just pulled that out of the seminar that I taught last year online. And as I mentioned above, we’re doing that seminar again and this will be some of the information that’ll be in there as well. I will also be sharing all kinds of info about the CBC and the metabolic panel, thyroid panel, lipid panel, iron panel, and much more. So, lots of great information in there. If you’d like to join us, I would love to have you. All you have to do is click the link inside the show notes to register. There’s also information in there if you are reading this podcast episode after September 16th, 2020, and we’ve already closed the registration. You can purchase the seminar notes separately, but there is no recording that goes with them. So, if you are reading this in time to register, the value is really high being inside the seminar, with everybody else kind of learning at the same time.


I’d love to have you either way. I’d love to have you join me. But if not, you can pick those notes up online and I’ll put the resources in there. Also, I want to give all of you reading or listening, the four slides that can be a resource guide for the B12, methylmalonic acid, and folate to show you what you can look for if those values are high or low. I’ve got those all done for you and they are in the show notes below. Click where it says “free resource” and you’ll see the resource guide for B12, methylmalonic acid, and folate discrepancies. Also, the link to the registration page for the Functional Blood Chemistry Seminar is there as well. I also have another link down below that has some more information about B12 which can be a great resource for you to give to your patients who want to maybe learn a little bit more.


I hope to see you inside the online seminar. Otherwise, enjoy this info. Thank you so much for joining me on The Clinical Entrepreneur Podcast. It’s my pleasure to be here with you. I love teaching clinicians about how to be better clinicians, but also how to run their businesses in a way that creates that foundation so that you can be an excellent clinician. Sometimes we can get clinically obese, and we forget that we have to run a business here as well. We have to be able to be profitable. We’ve got to pay the bills. We sometimes focus, we swing way over on this clinical side and we get obese. In other words, we have lots of clinical knowledge but sometimes we don’t always know how to run our business or if the business is profitable. As one of my mentors always says, the more money you make, the more impact you can have. And I believe that wholeheartedly.


So, I’m here to support you, clinically, but I’m also here to help you create that business that attracts the right patients and allows you to serve and impact even more people. Thank you again for listening. I can’t wait to see you next week on The Clinical Entrepreneur Podcast. Take care, my friend. See you then.




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