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 FOR ENERGY – AND MUCH MORE ⚡
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.
⚡ MYO-MAG BENEFITS ⚡
• ENERGY – Myo-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 RECOVERY – Myo-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-BEING – Myo-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 OVERVIEW ⚡
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.
⚡ MAGNESIUM, MALIC ACID (MALATE), B VITAMINS, AND MORE ⚡
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.
⚡ MYO-MAG CONSIDERATIONS & APPLICATIONS ⚡
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 ⚡
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
• 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.
⚡ MALIC ACID / MALATE ⚡
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 C4H6O5) made 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.”
⚡ MANGANESE ⚡
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.
⚡ MYO-MAG USAGE ⚡
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:
% Daily Value
Magnesium (Mg malate, diglycinate, carbonate)
Malic Acid (Mg malate)
Manganese (Mn diglycinate)
Vitamin B1 (Thiamin HCl)
Vitamin B2 (Riboflavin)
Vitamin B2 (Riboflavin-5′-phosphate)
Vitamin B6 (Pyridoxal-5′-phosphate)
Glycine (Mg and Mn diglycinate)
* 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.
⚡ CONCLUSION ⚡
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! ⚡
Think you take a complete multivitamin? Well, maybe not. Typical multivitamins simply do not provide enough nutrients for optimal health. Or for that matter, the proper forms and carriers of nutrients to do the job right—the all important task of providing you with essential nutrients for health. Not so easy these days? Well, Hank & Brian’s Mighty Multi-Vite! can help—a lot!
MIGHTY MULTI-VITE! DEFINES A COMPLETE MULTIVITAMIN
The task of providing you with a complete set of nutrients—as easily absorbed forms—is where Hank & Brian’s Mighty Multi-Vite! shines brightly in the world of #multivitamins. Quite simply, Dr. Hank Liers carefully formulated Mighty Multi-Vite! as the most advanced, complete multivitamin available. It uniquely includes a wide range of vitamins, minerals, cofactors, herbs, antioxidants, and Nrf2 activators (nutrients that allow your body to make its own antioxidants). This wide range of nutrients alone puts Mighty Multi-Vite! in a class by itself.
Calling HPDI’s Mighty Multi-Vite! “complete” is an understatement. While other multivitamins may contain more ingredients, Dr. Hank’s goal is not to “stuff” as many ingredients (or amounts) into Mighty Multi-Vite! as possible. That is a “shotgun” approach—Dr. Hank avoids it—that often results in too large capsules, huge tablets (“horse pills”), or eight-per-day dosages that are hard to consume—and even harder to stick with over time. You get the idea.
Instead, Dr. Hank carefully designed Mighty Multi-Vite! to include both a broad range of essential nutrients and abundant amounts of the most important nutrients for health in easily to assimilate forms using multiple carriers that give the body choices. For example, the body requires far smaller amounts of coenzyme B vitamins (which are the natural forms best utilized by cells) than conventional forms of B vitamins. This allows for more efficient dosing and does not “waste” space in the capsule allowing more room for other nutrients, like antioxidants and Nrf2 activators. In a nutshell, few multivitamins are so well balanced and designed carefully to give the body what it needs for optimal health. You get it all in just four (4) regular size capsules, daily. How easy is that?
As I mentioned, Mighty Multi-Vite! includes highly absorbable forms of nutrients. These include mineral carriers like Krebs Cycle bionutrients—carriers that feed the energy producing system in the body—including malates, ascorbates, aspartates, sebacates, citrates, and glycinates. Thus, we use magnesium malate, and calcium ascorbate and citrate. The whole point is that the body immediately recognizes and utilizes these forms.
In practice, Dr. Hank’s inclusion of the most absorbable forms and carriers means you actually absorb and assimilate more of the ingredients—whether vitamins, minerals, cofactors, antioxidants, herbs, or Nrf2 activators—than you would from the same old conventional forms and carriers (oxides, for example) found in many multivitamins, especially “off-the-shelf” or “one-a-day” type formulas. Many so-called “boutique” formulas use conventional forms and carriers. Who knew!?
To top it off, many advanced ingredients in Mighty Multi-Vite! (like Nrf2 activators) are nowhere to be found in the vast majority of multivitamins. You might not even know to look for them!
However, the biggest benefit of the science behind Mighty Multi-Vite! is how you feel when taking it. I really feel the difference. Your multivitamin should work for you and support your best health. If your multivitamin is not giving you what you need—or you can’t feel the difference it makes in your life—then why take it? Maybe it is better than nothing, but why settle for less when better options are available?
The single biggest reason I am a huge fan of Mighty Multi-Vite! is because I have taken it for more than 20 years. I have gained all the benefits it offers—for thousands of days—year after year. I am more than confident in its superior benefits not just for me, but because I have seen many other people gain benefits, and heard countless positive testimonies from happy customers. I know you can gain major benefits from it, too.
But wait, there’s more! Read the overview (below) for some nitty, gritty details distinguishing Dr. Hank’s design of Mighty Multi-Vite!. These not-so-little details can make all the difference for your good health.
MIGHTY MULTI-VITE! OVERVIEW
COMPLETE, BALANCED ESSENTIAL NUTRITION – Provides a full spectrum of nutrients exceptionally well balanced for creating and maintaining optimal heatlh. Mighty Multi-Vite! offers all of the most important vitamins along with minerals, cofactors, antioxidants, herbs, and Nrf2 activators.
RAPID, EASY ASSIMILATION – Incorporates the most bioavailable vitamin and mineral carriers most easily recognized and rapidly assimilated by your body. In addition, the formula uses multiple forms of mineral carriers to ensure assimilation. In addition, the capsule form (compared to tablets) speeds uptake because it does not require time for the body to break it down.
ENERGIZING – Includes coenzyme form vitamins and Krebs Cycle bionutrients that work with your body to create super high energy levels. Provides significantly higher levels of B vitamins than most multivitamins (especially coenzyme B vitamins). These vitamins are known for boosting energy, supporting the body during times of stress, and supporting nerve, heart, brain and immune system function.
FEATURES & BENEFITS OF MIGHTY MULTI-VITE! MULTIVITAMIN
• A full-spectrum of B-complex vitamins, most in coenzyme forms, as well as more conventional forms. Includes Vitamin B1 as thiamin HCl, Vitamin B2 as riboflavin and riboflavin-5’-phosphate, Vitamin B3 as niacinamide and niacin, Vitamin B5 as pantothenic acid, Vitamin B6 as pyridoxine HCl and pyridoxal-5’-phosphate, folate as L-5-methyltetrahydrofolate calcium (L-5-MTHF), Vitamin B12 as methylcobalamin, and biotin
• All of the most absorbable and usable forms of the fat-soluble vitamin group, including Vitamin A (as alpha & beta-carotene), Vitamin E (as d-alpha tocopherol succinate), Vitamin D3 (as cholecalciferol), and Vitamin K (as phytonadione (K1) and MK-7 (menaquinone-7) (K2))
• A complete and balanced supply of the most abundant carotenoids found in the body, including beta-carotene, alpha-carotene, lycopene and lutein
• A variety of the best-known herbal preparations, including whole grape extract (seeds, pulp, skin), turmeric (95% curcuminoids), broccoli sprouts powder, and octacosanol (from rice bran)
• All of the known essential minerals in forms readily absorbed and recognized by the body including calcium, magnesium, potassium, zinc, manganese, boron, copper, chromium, molybdenum, vanadium, and selenium
• Mineral carriers such as ascorbates, Krebs cycle bionutrients, and amino acids providing the body with important metabolic substrates and vitamins, including citrate, succinate, malate, glycinate, aspartate, sebacate, and Vitamin C
• Contains a wide range of antioxidants and Nrf2 activators including Buffered Vitamin C, Vitamin A, Vitamin E, Carotenoids, NAC, whole grape extract, curcuminoids, and broccoli sprouts
• Includes N-Acetyl-L-Cysteine (NAC), an important sulfur-containing amino acid supporting the body’s antioxidant and detoxification systems, and betaine HCl to support digestive processes
• Includes Choline and inositol which play a crucial role in all the cell membranes of the body, in brain function, and in liver function
• Includes Nrf2 transcription factor activators (i.e., Nrf2 activators), which are nutrients that direct cells to produce their own antioxidants, making your body an antioxidant production machine. Most multivitamins contain few, if any Nrf2 activators. Mighty Multi-Vite! is one of the few multivitamins whose design intentionally provides Nrf2 activators.
• Exclusion of the prooxidant minerals of iron and iodine which can lead to excessive free-radical production and PABA that sometimes adversely affects brain function in some individuals. (Note: we sell iodine formulas separately.)
• Capsule form ensures maximum absorption of ingredients
• Four-per-day full dosage allows for partial dosing for children, seniors, and pets
• Vegetarian formula (including capsule) suitable for vegetarians and vegans
• Exclusion of ingredients such as wheat, dairy, corn, soy, gluten, and egg having well-known antigenic properties and that may be associated with allergy or delayed hypersensitivity reactions
• A minimum of excipients, fillers, lubricants, etc. having deleterious effects in some individuals
• NON-GMO (no genetically modified organisms)
CONSIDER MIGHTY MULTI-VITE!
Most people don’t think too hard about their multivitamins. They focus on taking the supplement de jour (whatever supplements make headlines) or continue taking the same one-a-day multivitamin.
That is too bad because a multivitamin truly is the single most important nutritional supplement. We at HPDI place the multivitamin first—above all other supplements—in importance. Our Foundational Supplements system starts with a multivitamin because it is the only formula designed to provide the basic nutrients essential for health. That is, you can add other essential nutrients (like vitamin C or essential fats) to complete your regimen. But the multivitamin remains king (or queen) because it establishes your baseline nutrient intake. That is something is to consider when selecting the multivitamin you will take daily for the rest of your life.
Ask yourself: Is my multivitamin complete, providing all the most important nutrients I need for health? Is it easily absorbed using multiple, readily assimilated forms and usable carriers of those nutrients? Is it proven to work? Is it easy to take? Do I notice the effects?
If you answer “no” to any of these questions, or if you simply never think about it, then consider Hank & Brian’s Mighty Multi-Vite!. You should love your multivitamin because of how it supports your health. We think you will love Mighty Multi-Vite!.
As the year draws to a close, it is a good time to reflect on the past year, as well as to look forward to the New Year with respect to one’s health goals. This includes assessing your nutritional supplement regimen. There is more confusion about nutritional supplements than ever. With this in mind, we present “Megavitamin Myth-Busting” from Andrew W. Saul, PhD and Helen Saul Case from the Orthomolecular Medicine News Service to clear confusion about vitamins and other nutritional supplements, and set the record straight. Enjoy! ~
Commentary by Andrew W. Saul and Helen Saul Case
(Orthomolecular Medicine News Service, Dec 23, 2019)
People are so confused about endless internet vitamin legends. Now it’s time to be blunt and set the record straight.
The media says that taking vitamins will kill me. Is that so? NO.
It’s been said that the FDA does not regulate nutritional supplements. Is that true? NO. “FDA regulates both finished dietary supplement products and dietary ingredients.” [U.S. Food and Drug Administration, http://www.fda.gov/Food/DietarySupplements/ ]
Do I need special vitamin preparations for my body to absorb them? NO. With vitamins, there is usually no absorption issue. All animals need and absorb nutrients, including vitamins. If they didn’t, they’d be long extinct. The surface area of your small intestine, if all the nooks and crannies were flatted out, would be half the size of a regulation basketball court. There is ample opportunity for nutrient absorption.
Some persons have a genetic trait that makes it more difficult for them to convert dietary carotene into active vitamin A. Does this mean they must take preformed oil retinol A? NO. Even a poor converter can still make sufficient vitamin A from carotene if they eat lots of fruits and vegetables . . . which we should all be doing anyway.
Is niacin clinically incompatible for people with methylation issues? NO. Theoretically, perhaps. But Dr. Abram Hoffer, the world’s most experienced niacin physician, has said it is not clinically significant.
Aren’t B-vitamins so poorly absorbed that they need to be methylated? NO. Comparing their molecular weights with the simplest of all sugars, we find:
•Glucose (C6H12O6) weighs 180 grams/mole • Niacin (C6H5NO2) weighs 123 g/mol • Pyridoxine 169 g/mol • Pantothenic acid 219 g/mol • Biotin 244 g/mol • Thiamin 265 g/mol • Riboflavin 376 g/mol • Folic acid or folate 441 [Methylated may be better. However: 1) See: Bailey LB. Dietary reference intakes for folate: the debut of dietary folate equivalents. Nutr Rev. 1998;56(10):294-299. And 2) The Linus Pauling Institute says: “Unmetabolized folic acid concentrations returned to baseline levels at the end of the study, suggesting that adaptive mechanisms eventually converted folic acid to reduced forms of folate.” • Cobalamin 1,355 g/mol [methylated is probably better in this case]
Do I need to consume vitamin K-2 because K-1 in foods is ineffective? NO. Your body will make the conversion for you. John Cannell, MD, writes that the conversion “occurs through an intermediary molecule, vitamin K3, which is made in the intestine from vitamin K1. [Hirota Y, et al. J Biol Chem. 2013 Sep 30.] “[M]odern humans are deficient in K2 because they do not eat large quantities of vitamin K1 containing foods. If we look at Paleolithic humans, they probably got high amount of vitamin K2 from eating large quantities of kale and spinach-like foods, very high in K1, which then supplied their tissues with all the vitamin K2 they needed. [A]s far as getting enough vitamin K2, the best thing to do is eat your greens.”
I drink milk, and I spend time in the sunshine. Don’t I get plenty of vitamin D? NO. If your shadow is longer than you are, you are not making vitamin D from sunlight, says William Grant, PhD. Thus, little vitamin D is made by your body in the six colder months of the year. This is also true in the summer months if only exposed to sun mornings and afternoons. http://www.orthomolecular.org/resources/omns/v07n07.shtml
(Andrew W. Saul, OMNS founder and Editor-in-Chief, has coauthored four books with Abram Hoffer, MD, and is editor of the textbook The Orthomolecular Treatment of Chronic Disease. OMNS Assistant Editor Helen Saul Case is the author of The Vitamin Cure for Women’s Health Problems, Vitamins & Pregnancy: The Real Story, and Orthomolecular Nutrition for Everyone.)
Nutritional Medicine is Orthomolecular Medicine
Orthomolecular medicine uses safe, effective nutritional therapy to fight illness. For more information: http://www.orthomolecular.org
The peer-reviewed Orthomolecular Medicine News Service is a non-profit and non-commercial informational resource.
Comments and media contact: firstname.lastname@example.org OMNS welcomes but is unable to respond to individual reader emails. Reader comments become the property of OMNS and may or may not be used for publication.
I 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 contains the biochemically rare element cobalt positioned in the center of a chemical ring structure.
YOUR NEED FOR VITAMIN B12
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.
SOURCES OF VITAMIN B12
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.
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.
ABSORPTION OF VITAMIN B12
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 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 B 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.
FUNCTIONS AND ISSUES ASSOCIATED WITH VITAMIN B12 STATUS IN THE BODY
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.
MORE DETAILS ASSOCIATED WITH VITAMIN B12 STATUS IN THE BODY
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.
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.
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.
I previously published “Homocysteine Genetics – Coenzyme B Vitamins” in which I considered in-depth how homocysteine (an intermediate chemical in the Methylation Cycle) is formed from methionine, how genetics affects the metabolic pathways, and how B vitamins are used in metabolic pathways. I also wrote “Folate Ingredients – Folinic Acid & 5-MTHF” which discussed how coenzyme folate vitamins are far superior to the synthetic folic acid form. In today’s article, I take a broader view of the topic that encompasses the Methylation Cycle, genetics, and B vitamins.
THE METHYLATION CYCLE
The Methylation Cycle is considered to be one of the most important metabolic pathways in the human body. Its most important function is to provide methyl groups via SAM (S-adenosyl methionine) to hundreds of different body substrates. Methylation is continually occurring in the body, transforming many millions of molecules throughout the body every second. Molecules receive methyl groups, then separate and recombine continuously, transforming and reforming constantly in the ongoing process of life!
As a reminder of the pathways involved in the Methylation Cycle, the following figure provides a flow chart showing the details.
Figure 1. Metabolic Pathways in Methylation Cycle
A key purpose of this cycle is to provide methyl groups (CH3) needed by a broad range of of body functions (over 200 different functions). Examples include:
Influences the genetic expression that parents give their children and helps guide the development of the embryo.
Is needed by the nervous system to produce neurotransmitters and maintain the nerves.
Mobilizes fats and cholesterol so they do not accumulate where they are harmful, such as the arteries and liver.
Regulates hormones, including, estrogen, adrenaline, and melatonin.
Detoxifies harmful chemicals and histamine a prime substance involved in inflammation.
Helps repair damaged proteins in the cells so they can function properly.
Protects the DNA in the genome (genetic code) to reduce the chances of mutation.
Creates antioxidants used in the antioxidant defense system.
DESCRIPTION OF PATHWAYS WITHIN THE METHYLATION CYCLE
The overall flow of the Methylation Cycle begins with dietary methionine (an essential amino acid) which combines with ATP (adenosine triphosphate – body energy) to form SAM (S-adenosyl methionine) – the common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. When SAM transfers a methyl group to a body chemical the residue from this reaction leads to the production of homocysteine.
Homocysteine can be converted in the transsulfuration pathway that requires coenzyme vitamin B6 to produce cysteine, glutathione, taurine, and sulfates. These sulfur containing substances provide important antioxidant protection and detoxification functions in the body.
Homocysteine can be converted back to methionine through the betaine (trimethyl glycine) pathway which requires zinc and magnesium. This pathway also requires dietary betaine or choline which the body can convert into betaine.
Also, homocysteine can be converted back to methionine via the remethylation pathway which requires 5-MTHF, coenzyme vitamin B2 and methylcobalamin (B12).
It is important to understand that each of the pathways described above are able to be executed only in the presence of enzymes (shown in blue boxes in the diagram) created by specific genes in your genetic code. For example, Betaine-Homocysteine S-Methyltransferase (BHMT) is the enzyme required in the betaine pathway, Cystathione Beta Synthase (CBS) is the enzyme required in the transsulfuration pathway, and Methylenetetrahydrofolate Reductase (MTHFR) and Methionine Synthase (MS) are enzymes required in the remethylation pathway.
Assuming that you have perfect genetics (no mutations, SNPs, free radical damage, insertions/deletions, etc.), the proper functioning of these pathways are still subjected to the fact that the required vitamins and minerals (vitamin B6, vitamin B2, Folate, vitamin B12, zinc, magnesium, and betaine) need to be provided by your diet or from supplements for the body to function correctly.
In addition, exposure to high levels of toxins from your environment and high levels of stress require that the nutritional needs will be even higher for the pathways to work properly. For example, exposure to high levels of toxins requires that the transsulfuration pathway be more active possibly reducing the amount of available methionine to support necessary methyl transfer reactions.
For these reasons alone the consensus of knowledgeable practitioners is that you should be eating an organic whole foods diet, taking appropriate nutritional supplements, avoiding and eliminating toxins from food, water, and air (living in a clean environment), and avoiding an unduly stressful life. All of these actions fall into the category of Epigenetics which you generally have control over!! Doing these things alone could significantly balance the functioning of your Methylation Cycle and improve your health.
Unfortunately, few people have perfect genetics which often causes the various pathways in the Methylation Cycle to become imbalanced and unable to correct the dysregulation imposed upon the body. For example, the enzyme MTHFR can have heterozygous (single chromosome) genetic variations in up to 50% of certain populations and homozygous genetic variations (both chromosomes) in 10% or more of certain populations.
Some disorders that researchers have associated with MTHFR genetic variations include:
Chronic fatigue syndrome
High blood pressure
Irritable bowel syndrome
Migraines with aura
Nitrous oxide toxicity
Unexplained neurologic disease
This extensive list is highly significant and tells us that it is very important to have genetic testing done for the genes/enzymes in the Methylation Cycle pathway. I prefer the BodySync genetic test which evaluates the key Methylation Cycle genes plus many other important genes in a single test.
B VITAMINS AND MINERALS
We are strong believers that everyone should start their nutritional program by eating a balanced, organic, whole foods diet. We have been doing this ourselves for the past 30 years. Unfortunately, only a small percentage of people follow this advice and in most cases this leads to poor nutritional status that does not adequately support the body’s needs. This is especially true with respect to obtaining the nutrients needed to support the Methylation Cycle.
Nine of our family members and associates have taken the BodySync genetic test which evaluates the condition of 45 different enzymes including CBS, MTHFR (2 variations), MTR (related to B12 and 5-MTHF as they relate to methionine synthase – MS), and MTRR (related to maintaining B12 levels needed by the MTR enzyme). In every case the results showed at least 2 and up to 4 enzymes had genetic variations. These results indicate that the nutritional requirements for folate as 5-MTHF, vitamin B12 as methylcobalamin, vitamin B6, vitamin B2, magnesium and zinc will likely be significantly greater than normal.
Given the above information, it seems essential for good health to take nutritional supplements that provide the important nutrients. Below I will discuss various formulas that I have developed and refined over many years that are useful especially for the Methylation Cycle.
Please note that Health Products Distributors, Inc. (HPDI) is the preferred supplier of nutritional supplements by the BodySync genetic testing company.
When looking at the total needs the body has for nutrients that the body does not produce, including fat soluble vitamins (A, D (some), E, K1 and K2), vitamin C, B vitamins (B1, B2, B3, B5, B6, folate, B12, biotin, choline, and inositol), minerals (Ca, Mg, Zn, Se, Cu, Mn, Cr, Mo, K, boron, and vanadium), and betaine it only seems wise to include as a top priority a Multivitamin that includes all of these in what I term therapeutic amounts (carefully selected after evaluating thousands of research studies carried out over many years.)
In this context, it is important to recognize that every enzymatic reaction in the body requires mineral cofactors in order to carry out its function. A good multivitamin provides many of these required minerals.
Additionally, the multivitamin should contain ingredient forms that research has confirmed to be the most absorbable and usable by the body. These include coenzyme B vitamins, Krebs cycle (citrate, alpha-ketoglutarate, succinate, fumarate, & malate) minerals, and amino acid chelates.
In the context of supporting the Methylation Cycle we are looking for specific forms and amounts of B vitamins that can adequately provide the body’s needs. The means that there should be coenzyme folate as 5-MTHF of at least 400 mcg, coenzyme vitamin B-12 as methylcobalamin of at least 200 mcg, Vitamin B6 (including significant amounts of pyridoxal 5′ phosphate) of at least 40 mg, and Vitamin B2 (including significant amounts of riboflavin 5′ phosphate) of at least 25 mg. In addition, magnesium (100 mg) and zinc (at least 20 mg) should be provided.
Please note that the body’s requirements for magnesium is generally accepted by nutritional experts to be higher than 400 mg daily (and as high as 1,000 mg daily). For this reason we generally recommend that a person take supplemental magnesium (such as HPDI’s MYO-MAG) at levels over 400 mg daily.
The two multivitamin formulas Health Products Distributors provides for adults that meet these requirements (and more) are the Hank & Brian’s Mighty Multi-Vite and Multi Two (in both capsule and tablet forms). Click on the bottles below for technical details.
In situations where significant genetic variations are present it may be wise to add a B COMPLEX supplement to the MULTIVITAMIN to provide even larger amounts of the needed B vitamins. HPDI provides a B-Complex-50 product that includes significant amounts of coenzyme forms and contains 50 mg of Vitamin B1, 50 mg of Vitamin B2, 100 mg of Vitamin B3, 50 mg of Vitamin B6, 500 mcg of coenzyme folate (both folinic acid and 5-MTHF), 100 mcg of B12 (both methylcobalamin and hydroxocobalmin), 50 mg of Vitamin B5 (pantothenic acid), 500 mg of Biotin, 50 mg of choline, and 50 mg of inositol. Click on the bottle below for technical details.
FOLATE AS 5-MTHF
In situations where an inadequate diet is present and genetic testing indicates an MTHFR variation (especially a homozygous variation) Health Products Distributors provides a 5-MTHF folate supplement that easily absorbs into the body and can be directly used in combination with Vitamin B12 to convert homocysteine to methionine. Click on the bottle below for technical details.
5-MTHF 1 mg in veggie cap
B-12 as METHYLCOBALAMIN
It is often the case for older patients and vegetarians that Vitamin B12 is deficient. In these cases it is wise to supplement with a significant amount of methylcobalamin to ensure that the Methylation Cycle has sufficient to effectively convert homocysteine into methionine. Health Products Distributors Vitamin B12 contains 5 mg of methylcobalamin in sublingual lozenge form that supports excellent absorption even if swallowed and absorbed by diffusion. Click on the bottle below for technical details.
Magnesium and zinc are two important minerals used in the betaine pathway of the Methylation Cycle in which homocysteine is converted back to methionine.
In the body magnesium is involved in more than 400 essential metabolic reactions and is required by the adenosine triphosphate (ATP)-synthesizing protein in mitochondria. ATP, the molecule that provides energy for almost all metabolic processes, exists primarily as a complex with magnesium (MgATP). Therefore, it also is involved in converting methionine to SAM.
Over 300 different enzymes depend on zinc for their ability to catalyze vital chemical reactions. Zinc-dependent enzymes can be found in all known classes of enzymes.
Health Products Distributors provides 100 mg magnesium/vcap in its MYO-MAG supplement which is especially important in increasing ATP in the Krebs Cycle. This product also contains vitamin B1, vitamin B2, and vitamin B6 with substantial amounts of coenzyme forms and manganese. Click on the bottle below for technical details.
MYO-MAG with 100 mg magnesium per serving and key B vitamins.
Health Products Distributors provides 25 mg zinc/serving in its Double Zinc Plussupplement. This formula provides zinc in the picolinate and citrate forms as well as 3 mg of P5P (coenzyme B6). Click on the bottle below for technical details.
Double Zinc Plus supplement with P5P and 25 mg zinc
The Methylation Cycle is recognized as one of the most important metabolic pathways in the human body. When not properly supported by key B vitamins and minerals, the Methylation Cycle can become severely imbalanced which can lead to a very wide range of poor health conditions. Furthermore, genetic variations in the genes that produce important enzymes allowing the Methylation Cycle to function correctly lead to even further imbalances and greater possibility for conditions of poor health.
In this article, I have provided insight into how the Methylation Cycle works and how it can be significantly supported by lifestyle changes regarding diet and environment (Epigenetics) and by specific B vitamins and mineral supplements that I have developed over many years. In addition, we have shown that knowledge gained from genetic testing can further provide a critical understanding of your specific needs so that your health can be optimized.