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!.
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.
Looking for an advanced antioxidant formula? Already using or recommending vitamin C? Curious about cellular Nrf2 activation? Look no further than PRO-C™.
PRO-C™ is among the most effective antioxidant formulas available. It is an HPDI foundational supplement that works most effectively when used with multivitamins, essential fats, and superfoods. However, it is also an excellent standalone formula that can rapidly provide the body with extremely high protection from free radicals.
We ourselves have taken PRO-C daily for many years with excellent results. Our personal experience together with detailed feedback from health professionals and end-users affirms the effectiveness of PRO-C as a super-antioxidant–vitamin C-Nrf2 activator formula.
PRO-C provides 500 mg of buffered vitamin C per capsule (buffered with calcium, magnesium, and zinc) along with grape extract (seed, skin, pulp) and green tea extract (95% polyphenols). In addition, we include a special combination of the “network antioxidants” l-glutathione (reduced), n-acetyl-l-cysteine (NAC), r-lipoic acid, and selenium. Vitamin B2 and Vitamin B6 in coenzyme forms support the enzymatic effectiveness of the “network antioxidants”. The formula works so well because this combination of ingredients leverages the antioxidant power of vitamin C, grape extract, green tea extract, and the other nutrients to act synergistically in order to maximize effectiveness.
FORMULATION HISTORY AND THE SCIENCE BEHIND PRO-C™
What you may not know is the history of the development PRO-C and the scientific knowledge on which Dr. Hank Liers based his formulation of it.
Dr. Hank formulated his first product in 1989. It was a potent antioxidant formula he called PYC-C™ (sounds like “pixie”). PYC-C consisted of a combination of buffered Vitamin C (including magnesium, calcium, and zinc ascorbates) and pycnogenols from pine bark.
By 1997 Dr. Hank had gathered a great deal of new scientific information regarding green tea catechins and the nutrients termed “network antioxidants” by Dr. Lester Packer, director of Packer Lab at University of California, Berkeley. Beyond this information, Dr. Hank studied additional research regarding how various nutrients worked together synergistically. At that point, he was ready to formulate the new, improved PRO-C™ super antioxidant formula.
PRO-C combines the ingredients of PYC-C (now known as OPC-C™) and uses grape pulp, skin, and seed extract with green tea extract (with high polyphenols >95% and EpiGalloCatechinGalate (EGCG) >45%), n-acetyl-l-cysteine (NAC), reduced glutathione (GSH), R-lipoic acid, selenium, and coenzyme Vitamins B2 and B6.
HPDI launched PRO-C™ in late 1997. It rapidly became one of our best-selling products. Our customers raved about how effective it was for them if they felt like they were “coming down with something” (like a cold, flu, virus, infection, etc.). Greater skin elasticity greatly helped pregnant women avoid stretch marks and episiotomies. Today, we highly recommend its use together with our other Foundational Supplements to ensure optimal health and anti-aging effects.
THE PRO-C™ SUPER ANTIOXIDANT FORMULA
PRO-C™ super antioxidant formula is extremely synergistic, especially in so far as it increases the body’s ability to quench free radicals in its aqueous (i.e., water-based) compartments. Because antioxidants may become free radicals themselves after they have done their job, the body has developed an elaborate system for recovery of oxidized antioxidants.
Dr. Lester Packer was the primary researcher investigating the synergistic character of antioxidants. He made this statement in his interview with Dr. Richard Passwater after publication of Packer’s The Antioxidant Miracle (1999):
” [The major theme of] The Antioxidant Miracle is that antioxidants work in a coordinated manner. They interact with one another, and this interaction, which we like to call the antioxidant network, is very important to the overall antioxidant defense that we possess. The key members of the antioxidant network are vitamin E and vitamin C, but there are other participants in this network. These are thiol antioxidants, antioxidants that contain sulfur groups in the body. Glutathione perhaps is the best known of these, but there are other sulfur-containing antioxidants that also are very important.”
Dr. Packer continues:
“This whole antioxidant network works like an orchestra depending on individuals who have, of course, different complements of antioxidants depending upon their nutritional regimens and the individuality of their own body metabolisms. The idea behind having a network of antioxidants is that if one antioxidant happens to be deficient the others can compensate and still keep the antioxidant defense system strong.”
The following diagram shows some of the relationships in the antioxidant network and how they support each other.
Figure 1 – Dr. Packer’s Antioxidant Network
We see, for example, reduced glutathione (GSH) has the ability to reduce oxidized Vitamin C back to its unoxidized state. Vitamin C reduces oxidized Vitamin E back to its unoxidized state, and both reduces glutathione and spares it for other important functions, including detoxification and immune enhancement.
Many polyphenols (e.g., oligomeric proanthocyanidins (OPCs), anthocyanidins and catechins) found in red grape and green tea extracts spare Vitamin C and glutathione in the body, as well as operate as powerful antioxidants, anti-inflammatories, and connective tissue strengtheners.
Grapes provide antioxidant nutrients such as polyphenols, OPCs, anthocyans, and resveratrol.
R-Lipoic Acid (see abstracts below) operates as an antioxidant both in its oxidized and reduced states, reduces the oxidized forms of both Vitamin E and Vitamin C, and and has been shown to enhance glutathione levels. Because several of these substances are able to protect Vitamin E contained in cell membranes, this combination also has a significant beneficial effect on the fat soluble antioxidant status of the body!
The nutrients in PRO-C have been carefully selected and balanced to provide optimal effects, especially as related to free radical protection, detoxification, immune system enhancement, connective tissue strengthening, and reduction of inflammation. PRO-C therefore provides outstanding nutritional support in a wide variety of conditions of poor health, as well as acts to support and maintain a state of health and well-being.
It the last several years the research results on Nrf2 activators have become well known and products developed that take advantage of these nutrients. For details see our blog article Natural Phytochemical Nrf2 Activators for Chemoprevention. Researchers have been studying specifically how enzyme-activating substances such as OPCs and anthocyans activate a transcription factor known as Nrf2 that causes the body to endogenously produce higher levels of a wide variety of protective enzymes including superoxide dismutase (SOD), catalase, and glutathione peroxidase.
Although we did not know about Nrf2 activators in 1997 when we formulated PRO-C, we have subsequently learned that four of the ingredients in the formula have powerful Nrf2 activity. These include grape seed extract, green tea extract, NAC, and r-lipoic acid. With this knowledge, we now understand that PRO-C provides both powerful external antioxidants (with extremely high ORAC5.0 values) that support redox cycles within the body, but also provides ingredients that allow the body to endogenously produce powerful protective enzymes for even greater free-radical protection and health.
PRO-C™ ANTIOXIDANT FORMULA INGREDIENTS
PRO-C contains buffered vitamin C (in the form of powdered calcium, magnesium, and zinc ascorbates), high-potency grape extract (from grape pulp, skins, and seeds), green tea extract (with>95% polyphenols and >45% EGCG), reduced glutathione, N-Acetyl-L-Cysteine (NAC), R-lipoic acid, coenzyme forms of vitamin B2 (R5P) and vitamin B6 (P5P), and selenium.
Below we will discuss each ingredient and show some of the research that confirms its effectiveness.
Vitamin C typically is called l-ascorbic acid or ascorbate and is an essential nutrient for humans and other animal species. The term “vitamin C” refers to a number of vitamins that have vitamin C activity in animals, including ascorbic acid and its salts (e.g., magnesium ascorbate, calcium ascorbate, sodium ascorbate, etc.), and some oxidized forms such as dehydroascorbate and semidehydroascorbate.
Vitamin C is known to perform many critical functions within the body involving detoxification, tissue building, immune enhancement, pain control, and controlling or killing pathogenic organisms. It is also known to be helpful for wound and bone healing, healthy skin and eyes, fighting infections, stress control, toxic exposure, and repairing damaged tissue of all types. For much more information on the many benefits of Vitamin C see our blog article Vitamin C – An Amazing Nutrient.
Below are two abstracts that show some of the beneficial effects of Vitamin C when used with other network antioxidants:
ABSTRACT 1: Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration.
Sastre J, Asensi M, Gasco E, Pallardo FV, Ferrero JA, Furukawa T, Vina J
In: Am J Physiol (1992 Nov) 263(5 Pt 2):R992-5
We have studied the effect of exhaustive concentric physical exercise on glutathione redox status and the possible relationship between blood glutathione oxidation and blood lactate and pyruvate levels. Levels of oxidized glutathione (GSSG) in blood increase after exhaustive concentric physical exercise in trained humans. GSSG levels were 72% higher immediately after exercise than at rest. They returned to normal values 1 h after exercise. Blood reduced glutathione (GSH) levels did not change significantly after the exercise. We have found a linear relationship between GSSG-to-GSH and lactate-to-pyruvate ratios in human blood before, during, and after exhaustive exercise. In rats, physical exercise also caused an increase in blood GSSG levels that were 200% higher after physical exercise than at rest. GSH levels did not change significantly. Thus, both in rats and humans, exhaustive physical exercise causes a change in glutathione redox status in blood. We have also found that antioxidant administration, i.e., oral vitamin C, N-acetyl-L- cysteine, or glutathione, is effective in preventing oxidation of the blood glutathione pool after physical exercise in rats.
The effect of glutathione and vitamins A, C, and E on acute skin flap survival.
Hayden RE, Paniello RC, Yeung CS, Bello SL, Dawson SM
In: Laryngoscope (1987 Oct) 97(10):1176-9
Vitamins A, C, and E act as antioxidants and as free radical scavengers in biological systems. Glutathione is involved in several reactions in vitamin metabolism and also plays an important role in cell membrane protection against lipid peroxidation by free radicals. We sought to use these natural defense mechanisms against oxygen free radicals formed during reperfusion of ischemic skin flaps. An acute axial random skin flap model was utilized in the rat. Vitamins or glutathione were administered by oral gastric tube or intravenously in the perioperative period, and survival of the flap was measured at 1 week. Glutathione, beta-carotene, ascorbic acid and alpha-D- tocopherol showed mean flap survival of 84% to 89%, each of which was significantly improved over saline controls (67% p less than .0005). The mechanisms and biochemistry of these vitamins, and their interactions with other vitamins and with glutathione, are discussed, along with clinical implications of free radical scavenging and skin flap survival.
Grape extract (seeds, skin, pulp) contain highly bioavailable bioflavonoid complexes that in research studies have been shown to have powerful antioxidant capability. The Oligomeric Proanthocyanidins (OPCs) in grape seed extract are able to strengthen collagen fibers in aging or damaged connective tissue and can act as a preventative against connective tissue degradation.
Some research indicates that anthocyans, which are found in extracts of grape skin and stems (but not in grape seed extract), can reduce oxidized glutathione while at the same time become reduced themselves. In addition, extracts of grape skin and stems (but not those of grape seed extract) contain a material called trans-resveratrol that has been shown to have chemopreventive effects.
ABSTRACT 3: Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice. Bagchi D, Garg A, Krohn RL, Bagchi M, Bagchi DJ, Balmoori J, Stohs SJ
In: Gen Pharmacol (1998 May) 30(5):771-6
1. The comparative protective abilities of a grape seed proanthocyanidin extract (GSPE) (25-100 mg/kg), vitamin C (100 mg/kg), vitamin E succinate (VES) (100 mg/kg) and beta-carotene (50 mg/kg) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lipid peroxidation and DNA fragmentation in the hepatic and brain tissues, as well as production of reactive oxygen species by peritoneal macrophages, were assessed. 2. Treatment of mice with GSPE (100 mg/kg), vitamin C, VES and beta-carotene decreased TPA-induced production of reactive oxygen species, as evidenced by decreases in the chemiluminescence response in peritoneal macrophages by approximately 70%, 18%, 47% and 16%, respectively, and cytochrome c reduction by approximately 65%, 15%, 37% and 19%, respectively, compared with controls. 3. GSPE, vitamin C, VES and beta-carotene decreased TPA-induced DNA fragmentation by approximately 47%, 10%, 30% and 11%, respectively, in the hepatic tissues, and 50%, 14%, 31% and 11%, respectively, in the brain tissues, at the doses that were used. Similar results were observed with respect to lipid peroxidation in hepatic mitochondria and microsomes and in brain homogenates. 4. GSPE exhibited a dose-dependent inhibition of TPA- induced lipid peroxidation and DNA fragmentation in liver and brain, as well as a dose-dependent inhibition of TPA-induced reactive oxygen species production in peritoneal macrophages. 5. GSPE and other antioxidants provided significant protection against TPA-induced oxidative damage, with GSPE providing better protection than did other antioxidants at the doses that were employed.
ABSTRACT 4: Clinical and capillaroscopic evaluation of chronic uncomplicated venous insufficiency with procyanidins extracted from vitis vinifera
Costantini A, De Bernardi T, Gotti A
In: Minerva Cardioangiol (1999 Jan-Feb) 47(1-2):39-46
BACKGROUND: The pharmacological treatment of non-complicated chronic venous insufficiency is a current and well-debated topic. The introduction of new products with action on the venous system, improved knowledge on the physiopathology of venous insufficiency and the possibility provided by new analytical instruments, have given new impulse to the consolidation of the clinical value of phlebotonics in this indication. METHODS: In light of this, 24 patients with non-complicated chronic venous insufficiency were treated with oral administration of Oligomeric Proanthocyanidins (Pycnogenols-OPC) 100 mg/day. To evaluate the therapeutic efficacy of the treatment, an instrumental evaluation by optical probe capillaroscope was employed in addition to the traditional subjective clinical parameters: swelling, itching, heaviness and pain. The videocapillaroscope examination was performed at the lower third of the leg and the first toe. Edema in the capillaroscopic field, the number of observable capillaries and the capillary dilatation were the parameter chosen to evaluate the efficacy of treatment. All patients completed the study with no reports of adverse events during the period of observation. RESULTS: The results obtained show a positive clinical response (improved or absent symptoms) in over 80% of patients, with significant improvement of symptoms already evident after the first 10 days of treatment. The mechanism of action of the OPCs explains the rapid reduction of the swelling of the lower limbs and correlated with this are the other evaluable symptoms: heaviness and itching. Particularly striking results were observed for itching and pain which completely disappeared during the course of therapy in 80% and 53% of the patients respectively. Noteworthy is the good correlation between the clinical and instrumental data, with improvement in a total of 70% of patients. CONCLUSIONS: The results obtained in the course of this clinical experience, with evident improvement already during the first weeks of treatment, the absence of adverse events added to the benefit of a once-a-day administration, justify the use of OPC in the treatment of non-complicated chronic venous insufficiency.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor that regulates antioxidant response element (ARE)-driven phase II detoxification enzymes. In this study, induction of phase II enzymes via Nrf2/ARE activation in the cytoprotective effect of crude polyphenol extract (CPE), oligomeric procyanidin fraction (OPF), and polymeric procyanidin fraction (PPF) from defatted grape seeds in HepG2 cells was evaluated. Among these treatments, the treatment with PPF significantly increased Nrf2 protein expression in the nuclear fraction. Treating the samples increased heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) protein expression in a dose-dependent manner, and PPF significantly increased the levels of phase II enzymes. Cellular generation of reactive oxygen species (ROS) were effectively reduced by PPF. These results suggest that pretreatment with PPF shows a cytoprotective effect by inhibiting ROS production and inducing HO-1 and NQO1 expression via Nrf2 activation in HepG2 cells.
GREEN TEA EXTRACT
Green tea extract is obtained from the unfermented leaves of Camellia sinensis for which numerous biological activities have been reported including: antimutagenic, antibacterial, hypocholesterolemic, antioxidant, and protective against tumorigenesis. Below we have selected a few of the many abstracts we have on file showing the benefit of green tea extract.
Green tea leaves are high in antioxidant polyphenols and catechins.
ABSTRACT 6: Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in cancer chemoprevention.
Khan SG, Katiyar SK, Agarwal R, Mukhtar H
In: Cancer Res (1992 Jul 15) 52(14):4050-2
Following the oral feeding of a polyphenolic fraction isolated from green tea (GTP) in drinking water, an increase in the activities of antioxidant and phase II enzymes in skin, small bowel, liver, and lung of female SKH-1 hairless mice was observed. GTP feeding (0.2%, w/v) to mice for 30 days significantly increased the activities of glutathione peroxidase, catalase, and quinone reductase in small bowel, liver, and lungs, and glutathione S-transferase in small bowel and liver. GTP feeding to mice also resulted in considerable enhancement of glutathione reductase activity in liver. In general, the increase in antioxidant and phase II enzyme activities was more pronounced in lung and small bowel as compared to liver and skin. The significance of these results can be implicated in relation to the cancer chemopreventive effects of GTP against the induction of tumors in various target organs.
ABSTRACT 7: INHIBITORY EFFECT OF SIX GREEN TEA CATECHINS AND CAFFEINE ON THE GROWTH OF FOUR SELECTED HUMAN TUMOR CELL LINES. In: Anticancer Drugs (1996 Jun) 7(4):461-8
Institutional address: Department of Pharmacology and Toxicology College of Pharmacy University of Arizona Tucson 85721 USA.
Green tea is an aqueous infusion of dried unfermented leaves of Camellia sinensis (family Theaceae) from which numerous biological activities have been reported including antimutagenic, antibacterial, hypocholesterolemic, antioxidant, antitumor and cancer preventive activities. From the aqueous-alcoholic extract of green tea leaves, six compounds (+)-gallocatechin (GC), (-)-epicatechin (EC), (-)- epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)- epigallocatechin gallate (EGCG) and caffeine, were isolated and purified. Together with (+)-catechin, these compounds were tested against each of four human tumor cells lines (MCF-7 breast carcinoma, HT-29 colon carcinoma, A-427 lung carcinoma and UACC-375 melanoma). The three most potent green tea components against all four tumor cell lines were EGCG, GC and EGC. EGCG was the most potent of the seven green tea components against three out of the four cell lines (i.e. MCF-7 breast cancer, HT-29 colon cancer and UACC-375 melanoma). On the basis of these extensive in vitro studies, it would be of considerable interest to evaluate all three of these components in comparative preclinical in vivo animal tumor model systems before final decisions are made concerning which of these potential chemopreventive drugs should be taken into broad clinical trials.
GLUTATHIONE AND N-ACETYL-L-CYSTEINE (NAC)
Glutathione and NAC (a major precursor of glutathione) both provide important protection against toxins and free radicals, and can strengthen the immune system. Glutathione is considered to be one of the most important protective substances in the human body with almost 60% of liver detoxification accounted for by this key substance. In addition, glutathione is one of the most potent anti-viral substances known.
Some research has indicated that glutathione may not be able to enter easily into certain types of cells, but NAC is able to enter these cells and be converted into glutathione once inside the cell. Thus, the combination of glutathione and NAC appear to be more potent than either alone.
ABSTRACT 8 GSH rescue by N-acetylcysteine.
Ruffmann R Wendel A
In: Klin Wochenschr (1991 Nov 15) 69(18):857-62
Reduced glutathione (GSH) is the main intracellular low molecular weight thiol. GSH acts as a nucleophilic scavenger and as an enzyme-catalyzed antioxidant in the event of electrophilic/oxidative tissue injury. Therefore, GSH has a major role as a protector of biological structures and functions. GSH depletion has been recognized as a hazardous condition during paracetamol intoxication. Conversely, GSH rescue, meaning recovery of the protective potential of GSH by early administration of N-acetylcysteine (NAC), has been found to be life-saving. Lack of GSH and electrophilic/oxidative injury have been identified among the causes of the adult respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), and the acquired immunodeficiency syndrome (AIDS). Experimental and early clinical data (in ARDS) point to the role of NAC in the treatment of these conditions. Recently, orally given NAC has been shown to enhance the levels of GSH in the liver, in plasma, and notably in the bronchoalveolar lavage fluid. Rescue of GSH through NAC needs to be appreciated as an independent treatment modality for an array of different disease, all of which have one feature in common: pathogenetically relevant loss of GSH.
ABSTRACT 9 Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine.
Bridgeman MM Marsden M MacNee W Flenley DC Ryle AP
In: Thorax (1991 Jan) 46(1):39-42
N-acetylcysteine (600 mg/day) was given to patients by mouth for five days before bronchoscopy and bronchoalveolar lavage to determine whether N-acetylcysteine could increase the concentrations of the antioxidant reduced glutathione in plasma and bronchoalveolar lavage fluid. Bronchoalveolar lavage was performed 1-3 hours (group 2, n = 9) and 16-20 hours (group 3, n = 10) after the last dose of N-acetylcysteine and the values were compared with those in a control group receiving no N-acetylcysteine (group 1, n = 8). N-Acetylcysteine was not detected in plasma or lavage fluid. Plasma concentrations of cysteine, the main metabolite of N-acetylcysteine and a precursor of reduced glutathione, were greater in the groups receiving treatment (groups 2 and 3) than in group 1. Cysteine concentrations in lavage fluid were similar in the three groups. Concentrations of reduced glutathione were greater in both plasma and lavage fluid in group 2 than in group 1. These data suggest that N-acetylcysteine given by mouth is rapidly deacetylated to cysteine, with resulting increases in the concentrations of cysteine in plasma and of reduced glutathione in plasma and the airways, which thus temporarily increase the antioxidant capacity of the lung.
R-LIPOIC ACID / ALPHA-LIPOIC ACID
R-Lipoic Acid is normally made at low levels in the human body, where it functions primarily as an important metabolic nutrient in the conversion of pyruvic acid into acetyl coenzyme A. As such, it plays a crucial role in the metabolism of both fats and carbohydrates into energy. In addition, r-lipoic acid functions as an extremely powerful antioxidant capable of trapping many different types of free radicals in the body.
Because it is both water and fat soluble, lipoic acid is able to operate in a broader range of body tissues than most other antioxidants. Its small size allows lipoic acid to enter areas of the body not easily accessible to many other substances; this allows lipoic acid, for example, to enter the cell nucleus and prevent free-radical damage to DNA.
Because it is such a powerful antioxidant and can easily function as such in both a reduced and oxidized state, lipoic acid is able to protect other important antioxidants such as glutathione, Vitamin E, and Vitamin C. R-lipoic acid is also able to chelate heavy metals such as lead, cadmium, mercury, free iron, and free copper out of the body.
Below we provide relevant scientific abstracts from our database regarding R-Lipoic acid.
ABSTRACT 10: Alpha-Lipoic acid as a biological antioxidant.
Packer L Witt EH Tritschler HJ
In: Free Radic Biol Med (1995 Aug) 19(2):227-50
alpha-Lipoic acid, which plays an essential role in mitochondrial dehydrogenase reactions, has recently gained considerable attention as an antioxidant. Lipoate, or its reduced form, dihydrolipoate, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, hypochlorous acid, peroxyl radicals, and singlet oxygen. It also protects membranes by interacting with vitamin C and glutathione, which may in turn recycle vitamin E. In addition to its antioxidant activities, dihydrolipoate may exert prooxidant actions through reduction of iron. alpha-Lipoic acid administration has been shown to be beneficial in a number of oxidative stress models such as ischemia-reperfusion injury, diabetes (both alpha-lipoic acid and dihydrolipoic acid exhibit hydrophobic binding to proteins such as albumin, which can prevent glycation reactions), cataract formation, HIV activation, neurodegeneration, and radiation injury. Furthermore, lipoate can function as a redox regulator of proteins such as myoglobin, prolactin, thioredoxin and NF-kappa B transcription factor. We review the properties of lipoate in terms of (1) reactions with reactive oxygen species; (2) interactions with other antioxidants; (3) beneficial effects in oxidative stress models or clinical conditions.
Alpha-lipoic acid (α-LA) is an important antioxidant that is capable of regenerating other antioxidants, such as glutathione (GSH). However, the underlying molecular mechanism by which α-LA regenerates GSH remains poorly understood. The current study aimed to investigate whether α-LA regenerates GSH by activation of Nrf2 to alleviate cadmium-induced cytotoxicity in HepG2 cells. In the present study, we found that cadmium induced cell death by depletion of GSH through inactivation of Nrf2. Addition of α-LA to cadmium-treated cells reactivated Nrf2 and regenerated GSH through elevating the Nrf2-downstream genes γ-glutamate-cysteine ligase (γ-GCL) and GR, both of which are key enzymes for GSH synthesis. However, blocking Nrf2 with brusatol in the cells co-treated with α-LA and cadmium reduced the mRNA and the protein levels of γ-GCL and GR, thus suppressed GSH regeneration by α-LA. Our results indicated that α-LA activated Nrf2 signaling pathway, which upregulated the transcription of the enzymes for GSH synthesis and therefore GSH contents to alleviate cadmium-induced cytotoxicity in HepG2 cells.
Selenium has been shown by clinical research to be a key mineral in the body’s defenses against free radicals and has been shown to be a major factor in reducing the symptoms of HIV infections and in the prevention of tumors. Selenium is used in conjunction with glutathione to form the powerful enzyme glutathione peroxidase that is responsible for detoxification of peroxides formed during the process of aerobic metabolism in humans and other animals.
ABSTRACT 12 Serum selenium concentrations in rheumatoid arthritis.
In: Ann Rheum Dis (1991 Jun) 50(6):376-8
O’Dell JR, Lemley-Gillespie S, Palmer WR, Weaver AL, Moore GF, Klassen LW
Selenium is a trace element and an essential part of the enzyme glutathione peroxidase, which protects cells from oxidative damage. Selenium has been shown to have antiproliferative, anti-inflammatory, antiviral, and immune altering effects. Serum selenium concentrations in 101 patients with seropositive rheumatoid arthritis were found to be significantly lower than those in 29 normal, healthy controls (mean (SD) 148 (42) v 160 (25) micrograms/l) and also lower than those in eight patients with fibrositis (148 (42) v 166 (25) micrograms/l). It is speculated that serum selenium concentrations may modulate the effect of viral or other infections in subjects with the appropriate genetic background and in this way enhance the development or progression of rheumatoid arthritis.
ABSTRACT 13 Studies on selenium in top athletes.
Dragan I, Ploesteanu E, Cristea E, Mohora M, Dinu V, Troescu VS
In: Physiologie (1988 Oct-Dec) 25(4):187-90
The authors performed a controlled trial in 18 top athletes (9 weight lifters and 9 rowers, girls) in order to make evident some chronic and acute effects (antioxidant) of selenium. Nonprotein–SH (essential glutathione), lipid peroxides (MDA-malondialdehyde), glucose-6-phosphate dehydrogenases (G-6-PDH) and fructose-1,6- diphosphate aldolase in serum, have been recorded initially on basal conditions, after 3 weeks of treatment (100 micrograms/day selenium or placebo) and again after 3 weeks of treatment, also on basal conditions, when crossing over the groups (between a free interval of 10 days). In another trial we registered these parameters on basal conditions and after two hours of hard training accompanied by a per oral administration of 150 micrograms selenium (respectively placebo). The results show significant changes under selenium treatment of the peroxides, G-6-PDH and light changes, not significant of the nonprotein–SH, changes which could suggest an antioxidant effect of this element.
VITAMINS B2 and B6 IN COENZYME FORMS
Vitamin B2 as coenzyme riboflavin-5-phosphate is a key vitamin that supports the regeneration of glutathione (via glutathione reductase). Vitamin B6 as coenzyme pyridoxal-5-phosphate is a key vitamin that supports the ability of glutathione to combine with toxic substances (via glutathione transferase) in the process of eliminating them from the body. They are especially effective in their coenzyme forms which allows them to be directly utilized by the body starting in the intestinal tract.
MAGNESIUM, CALCIUM, AND ZINC
Magnesium, zinc, and calcium synergistically work with (and enhance the effects of) the other ingredients in PRO-C. Minerals are especially needed as active components of enzymes that drive metabolic activity. For example, magnesium is required in the functioning of more than 325 types of enzymes.
PRO-C™ SUPER ANTIOXIDANT FORMULA BENEFITS
HIGHLY EFFECTIVE VITAMIN C FORMULA PLUS ANTIOXIDANTS. A complete vitamin C formula, a powerful antioxidant Formula, and Nrf2 activator combined in a single advanced supplement!
POWERFUL, SYNERGISTIC FREE-RADICAL QUENCHING FORMULA. PRO-C™ components work together to quench free radicals in your body. Vitamin C enables grape seed extract to function more effectively, and conversely grape seed extract potentiates vitamin C. Green tea extract boosts ORAC (Oxygen Radical Absorbance Capacity) value.
PROVIDES SIGNIFICANT AMOUNTS OF POWERFUL NRF2 ACTIVATORS (from Grape Extract, Green Tea Extract, NAC, and R-Lipoic Acid) that stimulate the production of the body’s own protective antioxidants including superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase.
SUPERIOR, BUFFERED (NON-ACIDIC) FORM OF VITAMIN C. Mineral Ascorbates never acidify your body, keeping you pH balanced. Staying alkaline is an important element in maintaining a healthy body.
RAPID ASSIMILATION. Capsule form ensures rapid uptake and assimilation in the body. You may also empty capsule contents into water, food, or directly Into mouth, if desired. Good, mildly tart taste!
COMPOSITION OF PRO-C™ SUPER ANTIOXIDANT FORMULA
One (1) vegetarian capsule of PRO-C provides the following percentages of the Daily Value:
% Daily Value
Vitamin C (from mineral ascorbates)
BioVin® Grape Extract
Green Tea Extract
Calcium (from calcium ascorbate)
Magnesium (from magnesium ascorbate)
Zinc (from zinc ascorbate)
Vitamin B2 (from riboflavin-5′-phosphate)
Vitamin B6 (from pyridoxal-5′-phosphate)
Selenium (from l-selenomethionine)
* No established Daily Value
DIRECTIONS: As a dietary supplement take 1–3 capsules or more daily in divided doses (i.e., spread out over the day), or as recommended by a health care professional. It initially may be useful to take up to 6 capsules per day in divided doses for one week. The contents of the capsule may be emptied into juice or food, as needed.
INGREDIENTS: PRO-C™ SUPER ANTIOXIDANT FORMULA contains only the highest-quality USP grade magnesium ascorbate, USP grade calcium ascorbate, BioVin® grape extract (greater than 75% polyphenols, 93% OPC, greater than 3.5% anthocyanidins from grape pulp, skins, and seeds, and a small amount of trans resveratrol), green tea extract (95% min. polyphenols and 45% min. EGCG), l-glutathione (reduced), USP grade n-acetyl-l-cysteine, USP grade zinc ascorbate, r-(+)-lipoic acid, riboflavin-5′-phosphate, pyridoxal-5′-phosphate, l-selenomethionine, the smallest amounts of microcrystalline cellulose and silica in a vegetarian capsule.
PRO-C™ does not contain wheat, rye, oats, corn antigen, barley, gluten, soy, egg, dairy, yeast, sugar, sulfates, phosphates (other than coenzyme forms), fats, chlorides, GMOs, wax, preservatives, colorings, or artificial flavorings.
We previously published an article titled FOLATE INGREDIENTS – FOLINIC ACID & 5-MTHF in which we discuss how coenzyme folate vitamins are far superior to the synthetic folic acid form. In today’s article, I take a more in-depth look at how homocysteine is formed from methionine, how genetics affects the metabolic pathways, and how B vitamins are used in metabolic pathways.
One way to look at the metabolic pathways of methionine (an essential amino acid) is that it provides a way for the body to convert this sulfur containing amino acid either to cysteine and its key by-products glutathione, taurine, and sulfates or allows remethylation back to methionine to occur using either the Folate Cycle or the Trimethyl glycine (betaine) pathways.
Figure 1 shows these metabolic pathways including the vitamins required at each step including vitamin B6 (as P-5-P), methylcobalamin, and 5-methyltetrahydrofolate (5-MTHF). In addition, it shows the key enzymes produced by the body at each step. These enzymes include CBS (cystathione beta synthase), BHMT (betaine homocysteine methyltransferase), MS (methionine synthase), and MTHFR (methylene tetrahydrofolate reductase).
Figure 1. Metabolic Pathways in Methionine and Homocysteine Metabolism
HEALTH ISSUES ASSOCIATED WITH HIGH HOMOCYSTEINE LEVELS
It is highly important that the various metabolic pathways function correctly to keep homocysteine at healthy levels (6–8 µmol/L). Unfortunately, high levels of homocysteine in the body (10–20 µmol/L) are a factor in a wide range of health issues, including:
Greater risk for heart problems, including coronary artery disease, heart attacks, stroke, high blood pressure, congestive heart failure, and abnormal cholesterol levels. This is due to increased inflammation, sometimes due to blood clotting spontaneously, and because of blockages of the major arteries.
Mental abnormalities such as depression, anxiety, bipolar disorder, and other mental problems are more common among people with high homocysteine
Migraines and headaches in a significant percentage of the population
In those who suffer from high homocysteine due to having nutritional deficiencies anemia, aches and pains, hearing loss, age-related macular degeneration (ARMD), slowed development, and birth defects might also be possible
Greater risk for dementia, Alzheimer’s disease, brain atrophy, and other cognitive problems
In children, skeletal and developmental abnormalities including having a curved spine or protruding chest and rib cage. Some patients appear very tall and thin, and some might also have very long, thin “spider-like” toes and fingers.
Behavioral problems, including ADHD, autism and other learning disabilities
ROLE OF GENETICS IN HOMOCYSTEINE METABOLISM
Ten or more years ago, questions of how genetics enters into homocysteine metabolism were unlikely to be asked. However, in recent years DNA testing has advanced and is now available to everyone (for example, see my article about Bodysync’s genetic test, DISCOVERING NUTRITIONAL NEEDS THROUGH ADVANCED GENETIC TESTING.
You may have heard a great deal about MTHFR (methylene tetrahydrofolate reductase). This gene is involved in folate metabolism and has a central role in methylation processes like repair of and building new DNA in dividing cells.
In the remethylation pathway for conversion of homocysteine to methionine, MTHFR plays a key role in converting folate into 5-MTHF which is needed along with B12 as methylcobalamin in order for the conversion to take place. Genetic variations in MTHFR have been studied in depth. Of the many variations studies the most significant ones appear to be variations of C677C such as C677T (referred to as heterozygous) or T677T (referred to as homozygous). The heterozygous variant appears in about 30–50% of the population and causes somewhat less efficiency in the conversion of folic acid to 5-MTHF. However, the homozygous variation occurs in about 10% of the population and can have serious effects due to converting little homocysteine back to methionine.
Another variation in MTHFR is called A1298A. These variations are A1298C and C1298C and will have similar effects to the C677C variations. It was interesting to me when I recently analyzed my Bodysync genetic test results showing I carry the variation A1298C (heterozygous), which indicates I may not be effectively converting homocysteine back to methionine.
Additionally, my Bodysync genetic test results also indicate that I have heterozygous variations in the CBS enzyme shown in Figure 1, as well as heterozygous variations in MTR and MTRR enzymes, which are involved with B12 levels in the remethylation pathway. These results indicate that I need to take higher levels of methylcobalamin and 5-MTHF.
IMPORTANCE OF COENZYME FORMS AND PROPER AMOUNTS OF B VITAMINS
Many of the B vitamins on the market today unfortunately are in synthetic form. The body can only use the natural coenzyme forms effectively. For example, the body needs vitamin B6 in the form of P-5-P (pyridoxal-5-phosphate), folate in the form of L-5-MTHF, and B12 in the form of methylcobalamin for proper metabolism of methionine. In some cases the body can use the synthetic forms of pyridoxine HCl, folic acid, and cyanocobalamin but pays a cost (e.g., in time and energy) by having to convert synthetic forms to coenzyme forms.
Add to the prevalence of synthetic B vitamins, the fact that genetic deficiencies are more common than previously assumed, and it becomes clear that the coenzyme forms of B vitamins in the proper amounts are extremely important.
Fortunately, I have always believed it best to include as many coenzyme forms as possible in the nutritional supplements I formulate (over the past 27 years). For example, all HPDI multivitamins include coenzymes of B1, B2, B6, B12, and folate (as 5-MTHF and folinic acid). This is uncommon in most multivitamin formulas on the market. For this reason our supplements are ideally suited to the prevention or resolution of most genetic problems regarding homocysteine.
In addition, I have always chosen to include higher amounts than most multivitamins on the market. We also make available 5-MTHF one milligram (1 mg) capsules and methylcobalamin five milligram (5 mg) sublingual tablets. When genetic variations are in play as discussed above, then providing relatively higher amounts of coenzyme B vitamins that support important requirements in the body seems necessary.
Interestingly, several other nutrients are involved in the pathways involving methionine and homocysteine. These include zinc, magnesium, and Vitamin B2. Our multivitamin formulas and magnesium formulas, especially Myo-Mag with its coenzyme B1, B2, and B6, are recommended to support these nutrient needs. Finally, it has been found that N-Acetyl-L-Cysteine (NAC) can significantly lower homocysteine (by up to 50%), most likely because its gives the body an excellent source of cysteine without have to use methionine.
In this article, I have shown the value of the use of genetic testing and high-quality coenzyme B vitamins in resolving health issues associated with high values of homocysteine in the body.