Dr. Hank Liers, PhD myo-mag magnesium malic acid energizing formulaFred Liers PhD myo-mag magnesium malic acid energizing supplement

Got energy? That’s a big question. Many people are low on energy. A major cause of low energy is magnesium deficiency. In fact, studies show 50%–90% of people are deficient, often highly deficient. Magnesium boosts energy levels by feeding the body’s energy production system or Krebs cycle.

Myo-Mag— HPDI’s magnesium and malic acid formula — is designed to supercharge your energy production system to support a high energy lifestyle. Are you ready for what Myo-Mag can do for your energy? Well, it boosts energy, but does a lot more, too!

Getting enough magnesium is critical, of course. But it is equally important to get readily assimilable forms of magnesium and the synergistic nutrients required for its uptake and utilization. Myo-Mag provides optimal forms of magnesium and synergistic nutrients required to create energy (as ATP) for higher energy living. Myo-Mag feeds the body’s energy production system (Krebs cycle), which maximizes cellular energy. That is why users of Myo-Mag report far greater energy levels.


Myo-Mag supplies critical nutrients for energy production (as ATP) in the body. But it offers benefits far beyond boosting energy levels. Being a super magnesium formula, Myo-Mag optimizes all other beneficial effects of magnesium. In addition to energy production, magnesium is essential for muscle health, cardiovascular health, balancing calcium levels (and ensuring proper calcium uptake), as well as for proper function of more than 800 enzyme systems in the body.


ENERGYMyo-Mag supplies your cellular energy system with raw materials it can use immediately to produce energy for high vitality living. Myo-Mag can help you create energy fast—and naturally!

• MENTAL ENERGY – Just as Myo-Mag boosts physical energy, it can also boost mental energy. The energizing forms of magnesium and synergistic nutrients it provides create cellular energy the body can use for all purposes requiring energy.

MUSCLE RECOVERYMyo-Mag supports muscle health, muscle use, and muscle recovery. You might call Myo-Mag a muscle formula, and indeed “Myo” means “muscle” in Greek. Muscles that are properly nourished function well and are loose, not contracted, overly tight, or cramped. Muscles can benefit from Myo-Mag!

RELAXATION AND CALMING – In addition to being an “energy” production formula, Myo-Mag provides forms of magnesium and other nutrients that allow the body to relax. Muscle relaxation is a well known effect of magnesium. Also, the counterbalancing effect of magnesium on calcium in cells contributes to a relaxation effect. Too much calcium by itself (without being balanced) by magnesium can lead to muscle contraction and tension.

• GREATER SENSE OF WELL-BEINGMyo-Mag can provide an overall sense of well being. This is likely due both to the wide range of benefits and effects of magnesium (see list below) combined with the benefits of the synergistic nutrients it provides. For example, a combination of the known benefits of muscle relaxation, improved mood, and increased vitality can together contribute to an overall increased sense of well-being.

• CARDIOVASCULAR HEALTH – The heart is a muscle and gain major benefits from the right forms of magnesium, like other muscles

• HEADACHES – The ingredients in Myo-Mag are known to help headaches, including migraine headaches

• MANY OTHER BENEFITS – Due to its status as an exceptional magnesium & malic acid formula, Myo-Mag provides all benefits associated with magnesium (see list below), but also supercharges these benefits due to the malic acid (malate), B vitamins, and other synergistic nutrients.

myo-mag magnesium malic acid energizing formula


Myo-Mag is an advanced magnesium formula that supports metabolism, energy production (ATP), and optimal cellular function. It allows for rapid uptake and absorption of easily assimilated forms of magnesium. It also provides critical nutrients supporting energy production in the body. Because Myo-Mag rapidly boosts magnesium levels, individuals usually notice greater physical and mental energy, reduced fatigue, and often a greater sense of overall well being.


Myo-Mag contains ingredients participating in the production of ATP. One vegetarian capsule contains 100 mg of magnesium and over 300 mg of malic acid. Vitamin B1 is included as Thiamin HCl and vitamin B2 is included as both Riboflavin and Riboflavin 5′-phosphate. Also included are vitamin B6 in its pyridoxal 5′-phosphated coenzyme form, manganese (because high levels of magnesium can deplete the body of it), magnesium carbonate (a malic acid buffer), and glycine as the carrier for a portion of the magnesium and for the manganese.

Supplementing the diet with magnesium and malic acid may reverse conditions of low energy. Suggested daily amounts include 300–600 mg of magnesium and 1200–2400 mg of malic acid.


There are several key nutrients needed by mitochondria to manufacture ATP in the body. These include oxygen, magnesium, food substrate, ADP, and inorganic phosphate, as well as Vitamin B1, Vitamin B2, and Vitamin B6 in their phosphorylated (coenzyme) forms.

The body also requires malate (an important Krebs cycle intermediate) in order for most of these nutrients to function effectively in the process of ATP production. When adequate amounts of any of these nutrients are not present in the mitochondria, a vicious cycle can occur in which ATP is not created in amounts sufficient for proper cell function.

Insufficient amounts of ATP means that some B vitamins may not be adequately phosphorylated leading to improper metabolism and further reductions in ATP production. The much less efficient anaerobic production of ATP may be utilized to a greater extent. A balance point may be reached wherein the body produces only a fraction of the optimal amount of ATP. Under these conditions muscle weakness and fatigue may occur.

Vitamin B6 in its coenzyme form (pyridoxal-5’-phosphate) and magnesium are required for normal activity of malate dehydrogenase enzymes  involved in ATP production in the Krebs Cycle. In addition, the respiratory chain involved in ATP synthesis requires adequate amounts of the coenzyme  forms of B vitamins B1 and B2, which are the precursors of NAD and FAD. These two B vitamins, like B6, require a magnesium-dependent phosphate transfer reaction to become biologically active. Magnesium deficiency would therefore create a sluggish respiratory chain and a decreased efficiency in the transfer of reducing equivalents from the cytosol to the mitochondria. Supplementing the diet with magnesium and malic acid boosts energy production and thereby can reverse conditions of low energy.

In “Management of Fibromyalgia: Rationale for the Use of Magnesium and Malic Acid,” Abraham and Flechas reported that supplementing the diet with magnesium and malic acid may reverse such conditions of low energy (Jrnl of Nutritional Medicine 1992 3: 49–59). The recommended daily amounts include 300–600 mg of magnesium and 1200–2400 mg of malic acid.


Magnesium is a key ingredient in Myo-Mag which provides 100 mg per capsule in the form of magnesium malate. Magnesium plays a major role in energy production in the body. In particular, magnesium plays a critical role in key enzymatic reactions  for both aerobic and anaerobic glycolysis, which is the oxygen-dependent metabolic pathway that coverts glucose in to energy at ATP and NADH.

In order to appreciate the many benefits Myo-Mag offers, it helps to understand the effects and benefits of magnesium. Magnesium levels influence many physiological processes and functions. These include:

• Increases energy by greater production of ATP (adenosine triphosphate) in cells
• Supports production and function of over 800 enzyme systems in the body
• Relaxes muscles / reduces muscle tension
• Boosts vitality, endurance, and strength
• Improves cardiovascular / heart health (relaxes cardiac muscle)
• Relieves pain, including chronic pain
• Ideal for arthritis / fibromyalgia / joint pain
• Improves health of skin and mucous membranes
• Eases headaches and migraine headaches
• In sports medicine — replenishes Mg levels for energy (combats fatigue, and
soothes pain and sore muscles)
• Improves mood and reduces stress
• Increases memory and cognitive functions
• Boosts immune system
• Improves assimilation of calcium / builds stronger bones
• Balances calcium and magnesium levels in cells
• Proven antimicrobial and antiseptic
• Raises DHEA (dehydroepiandrosterone) levels naturally
• Eases menopause and premenstrual syndrome (pms)
• Supports healthy libido (and endocrine system)
• Anti-aging, rejuvenating, revitalizing
• Keeps cell membranes flexible
• Controls cholesterol production in the body
• Regulates blood sugar levels / needed for insulin production, transport, and
function in cells
• Supports antioxidant systems
Given the wide range of benefits conferred by magnesium on the human body, it becomes apparent that no level of deficiency is acceptable. Magnesium is simply critical for life and for health. It is far better to have more magnesium than less.
MYO-MAG contains three types of magnesium: magnesium malate, magnesium carbonate, and magnesium diglycinate. As noted, the malate form of magnesium offers the unique benefit of feeding the energy production system in the body. The magnesium carbonate in the formula acts as a buffering agent while magnesium glycinate is absorbed into the bloodstream thereby increasing absorption beyond the gastrointestinal tract.


Myo-Mag provides malic acid via magnesium malate, which breaks down in the body into about 80% malic acid and 15% magnesium. Malic acid is a compound (molecular formula C4H6O5made by all living organisms. Malic acid contributes to the sour taste of fruits, and its name derives from the Latin word for apple. Esters and salts of malic acid are known as malates. The malate anion is an intermediate in the citric acid cycle, or Krebs cycle, which produced energy (ATP) in the body.
According to Abraham and Flechas (1992): “Malate is the only metabolite of the citric acid cycle which correlates positively with physical activity.” They add: “Following endurance training of athletes, muscles were characterized by a 50% increase in the malate-aspartate redox shuttle enzymes, where malate plays a key role…When there is increased demand for ATP, there is also an increased demand and utilization of malate.”


Myo-Mag includes manganese because high levels of magnesium can deplete manganese. The classes of enzymes that have manganese cofactors is large and includes oxidoreductases, transferases, hydrolases, lyases, isomerases, ligases, lectins, and integrins. The reverse transcriptases of many retroviruses (though not lentiviruses such as HIV) contain manganese. The best-known manganese-containing polypeptides may be arginase and Mn-containing superoxide dismutase (Mn-SOD)

Manganese is an essential human dietary element. It is present as a coenzyme in several biological processes, which include macronutrient metabolism, bone formation, and free radical defense systems. It is a critical component in dozens of proteins and enzymes. The human body contains about 12 mg of manganese, mostly in the bones. The soft tissue remainder is concentrated in the liver and kidneys. In the human brain, the manganese is bound to manganese metalloproteins, most notably glutamine synthetase in astrocytes.


Taking 1–3+ Myo-Mag provide nutrients that help the body create energy. However, taking 3–6 (or more) Myo-Mag daily would meet the need for supplementing with 300–600 mg of magnesium and 1200–2400 mg of malic acid that is known to reverse conditions of low energy. We recommend starting low (1-2 capsules) and then gradually increasing the dosage. Myo-Mag is contained in a vegetarian capsule to ensure rapid assimilation.

COMPOSITION: One (1) vegetarian capsule of Myo-Mag provides the following percentages of the Daily Value:

Magnesium (Mg malate, diglycinate, carbonate) 100 mg 24%
Malic Acid (Mg malate)
300 mg *
Manganese (Mn diglycinate) 5 mg 217%
Vitamin B1 (Thiamin HCl) 10 mg 633%
Vitamin B2 (Riboflavin) 8 mg 615%
Vitamin B2 (Riboflavin-5′-phosphate) 2 mg 154%
Vitamin B6 (Pyridoxal-5′-phosphate) 5 mg 294%
Glycine (Mg and Mn diglycinate) 160 mg *

* No established Daily Value

DIRECTIONS: As a dietary supplement take 1–3+ capsules daily, or as directed by a health care professional.

INGREDIENTS: MYO-MAG only contains the highest-quality USP grade magnesium malate, magnesium diglycinate, magnesium carbonate, manganese diglycinate, thiamin HCl, riboflavin, pyridoxal-5′-phosphate, riboflavin-5′-phosphate, vegetable cellulose (capsule), microcrystalline cellulose, and silica.

MYO-MAG does not contain wheat, rye, oats, corn, barley, gluten, soy, egg, dairy, yeast, sugar, GMOs, sulfates, chlorides, wax, preservatives, colorings, or artificial flavorings.


Energy is important for life and health. And whether you realize it or not, large numbers of factors—some of which are beyond your control—conspire daily to rob you of energy. These factors may include low magnesium levels, stress to EMF exposure (like Wi-Fi or cell phone radiation), adverse dietary influences (like glyphosate/RoundUp), other chemical and/or environmental exposures, and even just lack of exercise. One of the easiest things to do is to take Myo-Mag to get the magnesium, malic acid, and synergistic nutrients you need to build greater energy levels. Get ready to blast off! ⚡



Myo-Mag Magnesium & Malic Acid Formula

HPDI Mineral Formulas

Myo-Mag on Amazon

HPDI Blog Articles

The Health Benefits of Oral Magnesium Using Myo-Mag by Dr. Hank Liers


Uses and Benefits of Magnesium Glycinate

Bioavailability of magnesium diglycinate vs magnesium oxide in patients with ileal resection
(J Parenter Enteral Nutr Sep-Oct 1994;18(5):430-5.)



Dr. Hank Liers, PhD vitamin B12 B-12 cobalamin methylcobalaminI previously wrote METHYLATION CYCLE, GENETICS, B VITAMINS in which I considered in-depth how the Methylation Cycle functions, how genetics affect metabolic pathways, and how B vitamins (including vitamin B12, folate, vitamin B6, and vitamin B2) are used in Methylation Cycle pathways. In today’s article, I take an in-depth view of what you need to know about vitamin B12, including the effects of not having sufficient amounts of Vitamin B12 in the body.

Vitamin B12 is one of eight B vitamins. It is the largest and most structurally complicated vitamin. It consists of a class of chemically related compounds (vitamers), all of which show physiological activity. It contains the biochemically rare element cobalt positioned in the center of a chemical ring structure.

Vitamin B12 (also called cobalamin) is a water-soluble vitamin that is involved in the metabolism of every cell of the human body. It is a cofactor in DNA synthesis, and in both fatty acid and amino acid metabolism. It is particularly important in the normal functioning of the nervous system via its role in the synthesis of myelin and in the maturation of developing red blood cells in the bone marrow.

vitamin B12

Vitamin B12 contains the biochemically rare element cobalt positioned in the center of a chemical ring structure.


Vitamin B12 deficiency is thought to be one of the leading nutritional deficiencies in the world. An extensive 2004 study showed that deficiency is a major health concern in many parts of the world, including the North America, Central and South America, India, and certain areas in Africa. It is estimated that 40 percent of people may have low levels of vitamin B12.

Vitamin B12 affects your mood, energy level, memory, nervous system, heart, skin, hair, digestion and more. It is a key nutrient regarding adrenal fatigue and multiple metabolic functions including enzyme production, DNA synthesis, and hormonal balance.

Because of vitamin B12’s extensive roles within the body, a vitamin deficiency can show up in many different symptoms, such as chronic fatigue, mood disorders such as depression, chronic stress, and low energy.


The only organisms to produce vitamin B12 are certain bacteria and archaea. Some of these bacteria are found in the soil around the grasses that ruminants eat. They are taken into the animal, proliferate, form part of their gut flora, and continue to produce vitamin B12.

Products of animal origin such as beef (especially liver), chicken, pork, eggs, dairy, clams, and fish constitute the primary food source of vitamin B12. Older individuals and vegans are advised to use vitamin B12 fortified foods and supplements to meet their needs.

vitamin B12 salmon

Salmon is a good source of Vitamin B12

Commercially, Vitamin B12 is prepared by bacterial fermentation. Fermentation by a variety of microorganisms yields a mixture of methylcobalamin, hydroxocobalamin, and adenosylcobalamin. Since multiple species of propionibacterium produce no exotoxins or endotoxins and have been granted GRAS status (generally regarded as safe) by the United States Food and Drug Administration, they are the preferred bacterial fermentation organisms for vitamin B12 production.

Methylcobalamin and 5-deoxyadenosylcobalamin are the forms of vitamin B12 used in the human body (called coenzyme forms). The form of cobalamin used in many some nutritional supplements and fortified foods, cyanocobalamin, is readily converted to 5-deoxyadenosylcobalamin and methylcobalamin in the body.

Hydroxocobalamin is the direct precursor of methylcobalamin and 5-deoxyadenosylcobalamin. In mammals, cobalamin is a cofactor for only two enzymes, methionine synthase (MS) and L-methylmalonyl-coenzyme A mutase (MUT).

Unlike most other vitamins, B12 is stored in substantial amounts, mainly in the liver, until it is needed by the body. If a person stops consuming the vitamin, the body’s stores of this vitamin usually take about 3 to 5 years to exhaust. Vitamin B12 is primarily stored in the liver as 5-deoxyadenosylcobalamin, but is easily converted to methylcobalamin.


Vitamin B12, bound to protein in food, is released by the activity of hydrochloric acid and gastric protease in the stomach. Intestinal absorption of vitamin B12 requires successively three different protein molecules: Haptocorrin, Intrinsic Factor and Transcobalamin II. If there are deficiencies in any of these factors absorption of Vitamin B12 can be seriously decreased.

When vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and, thus, does not require the separation from food protein step. Free vitamin B12 then combines with intrinsic factor, a glycoprotein secreted by the stomach’s parietal cells, and the resulting complex undergoes absorption within the distal ileum by receptor-mediated endocytosis.

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).

Vitamin B12 – 5 mg methylcobalamin sublingual lozenge

Vitamin B12 – 5 mg Methylcobalamin sublingual lozenge.


Vitamin B12 deficiency can be difficult to detect, especially since the symptoms of a vitamin B12 deficiency can be similar to many common symptoms, such as feeling tired or unfocused, experienced by people for a variety of reasons.

Vitamin B12 deficiency is commonly associated with chronic stomach inflammation, which may contribute to an autoimmune vitamin B12 malabsorption syndrome called pernicious anemia and to a food-bound vitamin B12 malabsorption syndrome. Poor absorption of vitamin may be related to coeliac disease. Impairment of vitamin B12 absorption can cause megaloblastic anemia and neurologic disorders in deficient subjects. In some cases, permanent damage can be caused to the body when B12 amounts are deficient.

It is noteworthy that normal function of the digestive system required for food-bound vitamin B12 absorption is commonly impaired in individuals over 60 years of age, placing them at risk for vitamin B12 deficiency.

A diagnosis of vitamin B12 deficiency is typically based on the measurement of serum vitamin B12 levels within the blood. However, studies show that about 50 percent of patients with diseases related to vitamin B12 deficiency have normal B12 levels when tested. This can cause individuals to ignore taking in adequate levels of vitamin B12 with potential serious consequences.


  • Vitamin B12 or cobalamin plays essential roles in folate metabolism and in the synthesis of the citric acid cycle intermediate, succinyl-CoA.
  • Vitamin B12 deficiency is commonly associated with chronic stomach inflammation, which may contribute to an autoimmune vitamin B12 malabsorption syndrome called pernicious anemia and to a food-bound vitamin B12 malabsorption syndrome. Impairment of vitamin B12 absorption can cause megaloblastic anemia and neurologic disorders in deficient subjects.
  • Normal function of the digestive system required for food-bound vitamin B12 absorption is commonly impaired in individuals over 60 years of age, placing them at risk for vitamin B12 deficiency.
  • Vitamin B12 and folate are important for homocysteine metabolism. Elevated homocysteine levels in blood are a risk factor for cardiovascular disease (CVD). B vitamin supplementation has been proven effective to control homocysteine levels.
  • The preservation of DNA integrity is dependent on folate and vitamin B12 availability. Poor vitamin B12 status has been linked to increased risk of breast cancer in some, but not all, observational studies.
  • Low maternal vitamin B12 status has been associated with an increased risk of neural tube defects (NTD), but it is not known whether vitamin B12 supplementation could help reduce the risk of NTD.
  • Vitamin B12 is essential for the preservation of the myelin sheath around neurons and for the synthesis of neurotransmitters. A severe vitamin B12 deficiency may damage nerves, causing tingling or loss of sensation in the hands and feet, muscle weakness, loss of reflexes, difficulty walking, confusion, and dementia.
  • While hyperhomocysteinemia may increase the risk of cognitive impairment, it is not clear whether vitamin B12 deficiency contributes to the risk of dementia in the elderly. Although B-vitamin supplementation lowers homocysteine levels in older subjects, the long-term benefit is not yet known.
  • Both depression and osteoporosis have been linked to diminished vitamin B12 status and high homocysteine levels.
  • The long-term use of certain medications, such as inhibitors of stomach acid secretion, can adversely affect vitamin B12 absorption.
  • Vitamin B12 is required for proper red blood cell formation, neurological function, and DNA synthesis.


1. Vitamin B12 is required for proper red blood cell formation, neurological function, and DNA synthesis. Vitamin B12 as methylcobalamin functions as a cofactor for methionine synthase. Methionine synthase (MS) catalyzes the conversion of homocysteine to methionine. Methionine along with ATP is required for the formation of S-adenosylmethionine (SAMe), a universal methyl donor for almost 100 different substrates, including DNA, RNA, hormones, proteins, and lipids.
2. Vitamin B12 as 5-deoxyadenosylcobalamin functions as a cofactor along with L-methylmalonyl-CoA mutase (MUT) to convert L-methylmalonyl-CoA to succinyl-CoA in the degradation of propionate, an essential biochemical reaction in fat and protein metabolism. Succinyl-CoA is also required for hemoglobin synthesis.
Metabolic Pathway


3. Vitamin B12, bound to protein in food, is released by the activity of hydrochloric acid and gastric protease in the stomach. When synthetic vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and, thus, does not require this separation step. Free vitamin B12 then combines with intrinsic factor, a glycoprotein secreted by the stomach’s parietal cells, and the resulting complex undergoes absorption within the distal ileum by receptor-mediated endocytosis. 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).

4. Pernicious anemia is an autoimmune disease that affects the gastric mucosa and results in gastric atrophy. This leads to the destruction of parietal cells, achlorhydria, and failure to produce intrinsic factor, resulting in vitamin B12 malabsorption. If pernicious anemia is left untreated, it causes vitamin B12 deficiency, leading to megaloblastic anemia and neurological disorders, even in the presence of adequate dietary intake of vitamin B12.

5. Vitamin B12 status is typically assessed via serum or plasma vitamin B12 levels. Values below approximately 170–250 pg/mL (120–180 picomol/L) for adults indicate a vitamin B12 deficiency. However, evidence suggests that serum vitamin B12 concentrations might not accurately reflect intracellular concentrations. An elevated serum homocysteine level (values >13 micromol/L) might also suggest a vitamin B12 deficiency. However, this indicator has poor specificity because it is influenced by other factors, such as low vitamin B6 or folate levels. Elevated methylmalonic acid levels (values >0.4 micromol/L) might be a more reliable indicator of vitamin B12 status because they indicate a metabolic change that is highly specific to vitamin B12 deficiency.

6. Vitamin B12 deficiency is characterized by megaloblastic anemia, fatigue, weakness, constipation, loss of appetite, and weight loss. Neurological changes, such as numbness and tingling in the hands and feet, can also occur . Additional symptoms of vitamin B12 deficiency include difficulty maintaining balance, depression, confusion, dementia, poor memory, and soreness of the mouth or tongue. The neurological symptoms of vitamin B12 deficiency can occur without anemia, so early diagnosis and intervention is important to avoid irreversible damage. During infancy, signs of a vitamin B12 deficiency include failure to thrive, movement disorders, developmental delays, and megaloblastic anemia. Many of these symptoms are general and can result from a variety of medical conditions other than vitamin B12 deficiency.

7. Typically, vitamin B12 deficiency is treated with vitamin B12 injections, since this method bypasses potential barriers to absorption. However, high doses of oral vitamin B12 can also be effective. The authors of a review of randomized controlled trials comparing oral with intramuscular vitamin B12 concluded that 2,000 mcg (I like 5,000 mcg) of oral vitamin B12 daily, followed by a decreased daily dose of 1,000 mcg and then 1,000 mcg weekly and finally, monthly might be as effective as intramuscular administration. Overall, an individual patient’s ability to absorb vitamin B12 is the most important factor in determining whether vitamin B12 should be administered orally or via injection. In most countries, the practice of using intramuscular vitamin B12 to treat vitamin B12 deficiency has remained unchanged.

8. Large amounts of folate can mask the damaging effects of vitamin B12 deficiency by correcting the megaloblastic anemia caused by vitamin B12 deficiency without correcting the neurological damage that also occurs. Moreover, preliminary evidence suggests that high serum folate levels might not only mask vitamin B12 deficiency, but could also exacerbate the anemia and worsen the cognitive symptoms associated with vitamin B12 deficiency. Permanent nerve damage can occur if vitamin B12 deficiency is not treated. For these reasons, folate intake from fortified food and supplements should not exceed 1,000 mcg daily in healthy adults.

Groups at Risk of Vitamin B12 Deficiency

The main causes of vitamin B12 deficiency include vitamin B12 malabsorption from food, pernicious anemia, postsurgical malabsorption, and dietary deficiency. However, in many cases, the cause of vitamin B12 deficiency is unknown. The following groups are among those most likely to be vitamin B12 deficient.

Older adults: Atrophic gastritis, a condition affecting 10%–30% of older adults, decreases secretion of hydrochloric acid in the stomach, resulting in decreased absorption of vitamin B12. Decreased hydrochloric acid levels might also increase the growth of normal intestinal bacteria that use vitamin B12, further reducing the amount of vitamin B12 available to the bodY.

Individuals with atrophic gastritis are unable to absorb the vitamin B12 that is naturally present in food. Most, however, can absorb the synthetic vitamin B12 added to fortified foods and dietary supplements. As a result, the IOM recommends that adults older than 50 years obtain most of their vitamin B12 from vitamin supplements or fortified foods. However, some elderly patients with atrophic gastritis require doses much higher than the RDA to avoid subclinical deficiency.

Individuals with pernicious anemia: Pernicious anemia, a condition that affects 1%–2% of older adults, is characterized by a lack of intrinsic factor. Individuals with pernicious anemia cannot properly absorb vitamin B12 in the gastrointestinal tract. Pernicious anemia is usually treated with intramuscular vitamin B12. However, approximately 1% of oral vitamin B12 can be absorbed passively in the absence of intrinsic factor, suggesting that high oral doses of vitamin B12 might also be an effective treatment.

Individuals with gastrointestinal disorders: Individuals with stomach and small intestine disorders, such as celiac disease and Crohn’s disease, may be unable to absorb enough vitamin B12 from food to maintain healthy body stores. Subtly reduced cognitive function resulting from early vitamin B12 deficiency might be the only initial symptom of these intestinal disorders, followed by megaloblastic anemia and dementia.

Individuals who have had gastrointestinal surgery: Surgical procedures in the gastrointestinal tract, such as weight loss surgery or surgery to remove all or part of the stomach, often result in a loss of cells that secrete hydrochloric acid and intrinsic factor. This reduces the amount of vitamin B12, particularly food-bound vitamin B12, that the body releases and absorbs. Surgical removal of the distal ileum also can result in the inability to absorb vitamin B12. Individuals undergoing these surgical procedures should be monitored preoperatively and postoperatively for several nutrient deficiencies, including vitamin B12 deficiency.

Vegetarians: Strict vegetarians and vegans are at greater risk than lacto-ovo vegetarians and non-vegetarians of developing vitamin B12 deficiency because natural food sources of vitamin B12 are limited to animal foods. Fortified breakfast cereals and fortified nutritional yeasts are some of the only sources of vitamin B12 from plants and can be used as dietary sources of vitamin B12 for strict vegetarians and vegans. Fortified foods vary in formulation, so it is important to read the Nutrition Facts labels on food products to determine the types and amounts of added nutrients they contain.

Pregnant and lactating women who follow strict vegetarian diets and their infants: Vitamin B12 crosses the placenta during pregnancy and is present in breast milk. Exclusively breastfed infants of women who consume no animal products may have very limited reserves of vitamin B12 and can develop vitamin B12 deficiency within months of birth. Undetected and untreated vitamin B12 deficiency in infants can result in severe and permanent neurological damage.

The American Dietetic Association recommends supplemental vitamin B12 for vegans and lacto-ovo vegetarians during both pregnancy and lactation to ensure that enough vitamin B12 is transferred to the fetus and infant. Pregnant and lactating women who follow strict vegetarian or vegan diets should consult with a pediatrician regarding vitamin B12 supplements for their infants and children.

Health Risks from Excessive Vitamin B12

The IOM did not establish a UL for vitamin B12 because of its low potential for toxicity. In Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, the IOM states that “no adverse effects have been associated with excess vitamin B12 intake from food and supplements in healthy individuals”.

Findings from intervention trials support these conclusions. In the NORVIT and HOPE 2 trials, vitamin B12 supplementation (in combination with folic acid and vitamin B6) did not cause any serious adverse events when administered at doses of 0.4 mg for 40 months (NORVIT trial) and 1.0 mg for 5 years (HOPE 2 trial).

Interactions with Medications

Vitamin B12 has the potential to interact with certain medications. In addition, several types of medications might adversely affect vitamin B12 levels. A few examples are provided below. Individuals taking these and other medications on a regular basis should discuss their vitamin B12 status with their healthcare providers.

Chloramphenicol: Chloramphenicol (Chloromycetin®) is a bacteriostatic antibiotic. Limited evidence from case reports indicates that chloramphenicol can interfere with the red blood cell response to supplemental vitamin B12 in some patients.

Proton pump inhibitors: Proton pump inhibitors, such as omeprazole (Prilosec®) and lansoprazole (Prevacid®), are used to treat gastroesophageal reflux disease and peptic ulcer disease. These drugs can interfere with vitamin B12 absorption from food by slowing the release of gastric acid into the stomach. However, the evidence is conflicting on whether proton pump inhibitor use affects vitamin B12 status. As a precaution, healthcare providers should monitor vitamin B12 status in patients taking proton pump inhibitors for prolonged periods.

H2 receptor antagonists: Histamine H2 receptor antagonists, used to treat peptic ulcer disease, include cimetidine (Tagamet®), famotidine (Pepcid®), and ranitidine (Zantac®). These medications can interfere with the absorption of vitamin B12 from food by slowing the release of hydrochloric acid into the stomach. Although H2 receptor antagonists have the potential to cause vitamin B12 deficiency, no evidence indicates that they promote vitamin B12 deficiency, even after long-term use. Clinically significant effects may be more likely in patients with inadequate vitamin B12 stores, especially those using H2 receptor antagonists continuously for more than 2 years.

Metformin: Metformin, a hypoglycemic agent used to treat diabetes, might reduce the absorption of vitamin B12, possibly through alterations in intestinal mobility, increased bacterial overgrowth, or alterations in the calcium-dependent uptake by ileal cells of the vitamin B12-intrinsic factor complex. Small studies and case reports suggest that 10%–30% of patients who take metformin have reduced vitamin B12 absorption. In a randomized, placebo controlled trial in patients with type 2 diabetes, metformin treatment for 4.3 years significantly decreased vitamin B12 levels by 19% and raised the risk of vitamin B12 deficiency by 7.2% compared with placebo. Some studies suggest that supplemental calcium might help improve the vitamin B12 malabsorption caused by metformin, but not all researchers agree.


FROM: https://academic.oup.com/ajcn/article/71/2/514/4729184
Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring Study

The American Journal of Clinical Nutrition, Volume 71, Issue 2, 1 February 2000, Pages 514–522, https://doi.org/10.1093/ajcn/71.2.514


Background: Low vitamin B-12 status is prevalent among the elderly, but few studies have examined the association between vitamin B-12 status and intake.
Objective: We hypothesized that vitamin B-12 concentrations vary according to intake source.
Design: Plasma concentrations and dietary intakes were assessed cross-sectionally for 2999 subjects in the Framingham Offspring Study. The prevalence of vitamin B-12 concentrations <148, 185, and 258 pmol/L was examined by age group (26–49, 50–64, and 65–83 y), supplement use, and the following food intake sources: fortified breakfast cereal, dairy products, and meat.
Results: Thirty-nine percent of subjects had plasma vitamin B-12 concentrations <258 pmol/L, 17% had concentrations <185 pmol/L, and 9% had concentrations <148 pmol/L, with little difference between age groups. Supplement users were significantly less likely than non-supplement-users to have concentrations <185 pmol/L (8% compared with 20%, respectively). Among non-supplement-users, there were significant differences between those who consumed fortified cereal >4 times/wk (12%) and those who consumed no fortified cereal (23%) and between those in the highest and those in the lowest tertile of dairy intake (13% compared with 24%, respectively), but no significant differences by meat tertile. Regression of plasma vitamin B-12 on log of intake, by source, yielded significant slopes for each contributor adjusted for the others. For the total group, b = 40.6 for vitamin B-12 from vitamin supplements. Among non-supplement-users, b = 56.4 for dairy products, 35.2 for cereal, and 16.7 for meat. Only the meat slope differed significantly from the others.
Conclusions: In contrast with previous reports, plasma vitamin B-12 concentrations were associated with vitamin B-12 intake. Use of supplements, fortified cereal, and milk appears to protect against lower concentrations. Further research is needed to investigate possible differences in bioavailability.