B12 Deficiency: Uncovering the Silent Threat to Neurological and Vascular Health

In today’s episode of Daily Value, we take a closer look at a commonly overlooked but essential nutrient: vitamin B12. Known as cobalamin, vitamin B12 deficiency can lead to severe neurological, hematological, and cognitive issues if left unchecked. We’ll cover the causes behind this growing issue, from dietary intake to malabsorption.

Episode Talking Points:

• The role of B12 in nervous system function and red blood cell production.
• Causes of B12 deficiency, including dietary factors, autoimmune conditions, and genetic predispositions.
• Treatment approaches, including supplementation methods and the importance of early diagnosis.

https://pubmed.ncbi.nlm.nih.gov/38987879/ 

https://www.nature.com/articles/nrdp201740

Transcript

Speaker 0: 0:00

Hello everyone, welcome back to Daily Value. I'm William Wallace and today we'll be having an overview discussion of cobalamin deficiency or vitamin B12 deficiency. This is a condition that affects a growing number of individuals due to a variety of factors, including dietary intake and malabsorption. B12 deficiency is often overlooked, but its consequences can be severe, leading to neurological, hematological and cognitive issues. Today's episode will cover the pathophysiology of B12 deficiency, diagnostic challenges and best practices for achieving optimal B12 status based on the most recent research. Before we begin, please remember that this podcast is for educational purposes only and is not intended as medical advice. If you or someone you know has or is being treated for a B12 deficiency, please consult your primary healthcare professional before beginning or altering treatment. Now let's dive into some of the science behind B12 deficiency and its management.

Speaker 0: 1:06

Vitamin B12, or cobalamin as it's called, is an essential water-soluble vitamin that plays a crucial role in the functioning of the nervous system and the production of red blood cells. It acts as a cofactor in various biochemical processes, including DNA synthesis and the methylation cycle. B12 is primarily synthesized by certain bacteria and RK. Because of this, b12 is not really found in plant food products. Certain plant-based fermented foods and algae, like chlorella may contain B12, but in food it's primarily found in animal tissues, in ruminant animals. A ruminant animal is one that has a special digestive system designed to break down tough plant material like grass. They have a multi-chambered stomach, with the largest chamber being called the rumen. That's where bacteria and microbes help ferment and digest their food. Animals like cows, sheep and deer are what we would call ruminants, and they regurgitate food to chew it again, what we call chewing cud, to help with digestion. This process allows them to get more nutrients from plant-based diets than other animals that cannot easily digest plants. The fermentation of the food they eat allows them to get B12 into their system, which makes its way to their tissues, which we benefit from when we consume animal products as such.

Speaker 0: 2:29

In humans, b12 is primarily obtained through the consumption of animal products such as meat and dairy. When we do not consume enough vitamin B12 from food, supplementation may be warranted. However, b12 absorption is a complex process that involves multiple steps, including the production of what's called intrinsic factor by the stomach lining and its subsequent absorption in the ileum, which is part of the small intestine. Intrinsic factor is a protein made in the stomach that's essential for absorbing vitamin B12. Without intrinsic factor. Even if you eat plenty of B12-rich foods like meat or dairy, your body can't properly absorb B12. The vitamin.

Speaker 0: 3:08

There are certain autoimmune conditions like atrophic gastritis or pernicious anemia. The former can be caused by the latter, where the body produces antibodies against intrinsic factor. This can result in B12 malabsorption due to the absence of intrinsic factor and, eventually, b12 deficiency. There are three primary mechanisms through which one may develop a B12 deficiency. One would be a dietary deficiency. This is the most common cause of B12 deficiency. It is insufficient intake of B12-rich foods, particularly in populations that follow vegetarian or vegan diets. B12 absorption can also decline with age due to decreased gastric acid production, which is necessary to release B12 from food. Two would be malabsorption. Autoimmune conditions that are characterized by the destruction of gastric parietal cells that produce intrinsic factor can lead to B12 malabsorption. Additionally, gastrointestinal surgeries like gastric bypass and diseases such as Crohn's disease also impair B12 absorption. Three would be drug use. Chronic use of drugs like proton pump inhibitors and acids and drugs like metformin, as well as recreational nitrous oxide, can deplete B12 levels by interfering with its metabolism, can deplete B12 levels by interfering with its metabolism.

Speaker 0: 4:35

Two lesser understood mechanisms of B12 deficiency may be genetic familial deficiency, meaning traits that are inherited through genetic mutations or predispositions passed down from parents to offspring. The second would be epigenetic causes. These involve changes in gene expression without altering the underlying DNA sequence. These changes can be influenced by environmental factors, lifestyle or diet and may not necessarily be passed down from generation to generation. Interestingly, past research in this area has shown that children of some families with normal vitamin B12 intake present with B12 deficiency, children of some families with normal vitamin B12 intake present with B12 deficiency. In these cases, it was found that B12 deficiency was present in the mother during pregnancy. It's possible that may lead to what are called epigenetic alterations in children which negatively impact gastrointestinal B12 absorption later in life. This might fall under what's called the transgenerational effect of possibilities. On the other hand, genetics can significantly impact how much vitamin B12 you have in your body. There are 15 genetic mutations related to the absorption, transport and metabolism of B12 that can affect B12 levels. One well-known gene, fut2, or the fucosal transferase 2, gene FUT2, or the fucosal transferase 2, can influence your total B12 levels, but it mostly increases the amount of inactive B12 by 10 to 25 percent rather than the active form that your body uses. That's called holotranscobalamin.

Speaker 0: 6:04

Unfortunately, many clinical symptoms of B12 deficiency are nonspecific. Many individuals with B12 deficiency present with neurological symptoms. These include numbness and tingling in the hands and feet, often described as pins and needles. Over time, it can cause balance problems and difficulty walking due to nerve damage. People may also experience memory loss, confusion and mood changes, including depression and irritability.

Speaker 0: 6:29

Another presentation of B12 deficiency is a type of anemia in the form of megaloblastic anemia, which is caused by pernicious anemia. Pernicious anemia, again, is an autoimmune condition where the body attacks the cells in the stomach that produce intrinsic factor, a protein needed to absorb vitamin B12. Without intrinsic factor, the body can't absorb enough B12, leading to a deficiency. This lack of B12 affects the production of red blood cells, causing them to become large and immature, a condition known as megaloblastic anemia. These oversized red blood cells can't function properly, leading to symptoms like fatigue, weakness and neurological issues. A folate deficiency can also cause megaloblastic anemia.

Speaker 0: 7:13

Most people in Western countries with B12 deficiency do not present with anemia or macrosytosis, that's when red blood cells are larger than normal. In fact, anemia is present in fewer than one-fifth of people with a vitamin B12 deficiency. It's not entirely known why some people with B12 deficiency present with neurological symptoms and some develop megaloblastic anemia. One of the key issues in managing B12 deficiency is that diagnosis can be complex due to nonspecific symptoms and variability in laboratory results. Again, common symptoms include neurological. This includes peripheral neuropathy, memory problems and cognitive impairment. There are hematological symptoms such as macrocytic anemia, fatigue and weakness, and there are also psychological symptoms that include mood swings, depression and irritability.

Speaker 0: 8:04

The most common biomarkers used to diagnose a vitamin B12 deficiency include methylmalonic acid and total homocysteine. These markers become elevated in vitamin B12 deficiency. Homocysteine these markers become elevated in vitamin B12 deficiency, reflecting impaired energy metabolism and methylation respectively. However, their use is complicated by factors such as kidney function and certain medications like antibiotics that can also influence their levels. Methylmalonic acid is not a very sensitive marker of B12 deficiency. It may be more representative of not having a certain amount of another active form of cobalamin, that being adenosylcobalamin, also known as cobalamide. This active form of vitamin B12 is present in the mitochondria of a cell and is used by the enzyme methylmalonyl-CoA mutase to convert methylmalonyl-CoA into succinyl-CoA. As for homocysteine, that can also be elevated in a folate deficiency or a vitamin B6 deficiency. Thus, elevated methylmalonic acid or homocysteine may confirm B12 deficiency, but they may not.

Speaker 0: 9:09

Holotranscobalamin is another common biomarker. This is the active fraction of B12 in the blood and may offer better diagnostic accuracy than total serum B12, but it and may offer better diagnostic accuracy than total serum B12, but it's not widely available and still has some limitations. Holotranscobalamin is the active form of vitamin B12 that your body can actually use because it's bound to a transport protein that delivers it to your cells. On the other hand, serum cobalamin measures the total amount of vitamin B12 in your blood, but this includes both active and inactive forms, the inactive form being called haptochorin. So even if your serum B12 levels are normal, it doesn't necessarily mean your body has enough usable B12. Holotrans cobalamin gives a more accurate picture of how much B12 is available to support important functions like DNA production and red blood cell formation. While serum B12 levels are commonly used to screen for deficiency, their accuracy is limited. Many patients may present with symptoms even after their serum B12 levels are within normal range.

Speaker 0: 10:06

The treatment of vitamin B12 deficiency depends on its cause, whether due to dietary insufficiency or malabsorption. The human body stores between 1 and 5 milligrams of vitamin B12, and we lose anywhere from 1.4 to 5.1 micrograms of the vitamin per day. Healthy adults require anywhere from 4 to 7 micrograms of vitamin B12 a day to maintain normal levels. With age, absorption decreases, so elderly people may need more, and in fact, vitamin B12 is listed as a nutrient of public health concern in people over 65 years of age. In people with severe vitamin B12 deficiency, iv or intramuscular doses of B12 usually wipe out symptoms more rapidly and, once stabilized, maintenance may be switched to oral supplementation which, depending on the doctor prescribing, is usually given in the form of cyanocobalamin or a preparation of the two active forms of B12, that being methylcobalamin and adenosylcobalamin. It's worth noting that if someone has a B12 deficiency and is supplementing with many compounds, high doses of folate or folic acid can also mask a B12 deficiency, especially if anemia is present due to B12 deficiency. Now it's important to note that it is usually recommended in cases of symptomatic B12 deficiency due to malabsorption, that B12 be administered intramuscularly, as oral supplementation would be ineffective. Once treatment is started under these circumstances, it's usually suggested that it may be maintained for life or until a clinician says otherwise. I need to be very clear in stating that there is not enough evidence to suggest the best B12 dose and frequency for long-term health outcomes, as this will likely vary between individuals.

Speaker 0: 11:53

Treatment schemes and doses vary quite a bit from country to country. Treatment schemes and doses vary quite a bit from country to country. For instance, the Netherlands standard is to use 1000 micrograms of hydroxycobalamin via intramuscular injection twice weekly. In the UK this is usually given on alternate days. Hydroxycobalamin has replaced cyanocobalamin as the preferred treatment choice in many countries.

Speaker 0: 12:14

As hydroxycobalamin is retained in the body longer than cyanocobalamin, the dose and frequency chosen by one's clinician may take several months or even years to resolve symptoms, depending on the severity and length of the deficiency. Before treatment, it's suggested that, even once symptoms subside, that the dose or frequency of injection not be suddenly reduced, as to prevent a rapid symptom onset. The recommendation is to gradually increase the interval between doses over time while monitoring symptoms. The frequency of intramuscular injections once symptoms have subsided can range from twice weekly to once every two to three months, depending on the individual. It's important to note that cyanocobalamin in very high doses is contraindicated in people with impaired kidney function and that there's not a lot of data comparing different forms of vitamin B12 being used to treat a B12 deficiency on a large scale. It's also important to note that there are no studies available that would make it obvious which individuals could safely transition from intramuscular therapy to oral supplementation of B12.

Speaker 0: 13:21

The clinical goal of B12 therapy is to reverse symptoms and improve the patient's quality of life, rather than simply just normalizing serum B12 levels. Neurological symptoms in particular may take months or even years to resolve and in some cases may not fully disappear. Monitoring for recurrence of symptoms is crucial, as rapid reduction in injection frequency can lead to a symptom relapse. Some patients experience neuropathic symptoms that improve with B12 supplementation, even if they do not exhibit classic signs of deficiency in lab tests. For those patients, a therapeutic trial of B12 injections is usually recommended, especially if other causes of neuropathy have been ruled out.

Speaker 0: 14:04

While studies suggest that oral doses of 2,000 micrograms or more may be absorbed passively, intramuscular injections remain the standard of care for those with severe deficiency or malabsorption disorders. Lifelong supplementation is typically required for individuals with malabsorption. For patients who respond well to treatment, the frequency of injections may be reduced, but monitoring for symptom recurrence is essential. Co-balliman deficiency is a serious condition, but it's a treatable condition. Early diagnosis and individualized treatment are critical to prevent irreversible damage, particularly to the nervous system. In this case, whether through oral supplementation or intramuscular injections, restoring B12 levels can significantly improve quality of life and mitigate the long-term effects of deficiency. Thank you for tuning in to Daily Value. If you found today's episode informative, be sure to subscribe and share with others who might benefit. As always, stay healthy.