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 contains the biochemically rare element cobalt positioned in the center of a chemical ring structure.
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.
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.
HPDI's sponsored athlete Irena Ossola has been a bike tour leader in Italy this summer and fall. During that time, she scaled back her nutritional supplement regimen. This is partly because the summer and fall period is one of rest from high-intensity competitive bike training—and because her training for the new racing season has not yet begun. However, she recorded her observations regarding nutritional supplements. She concludes they are important whether or not she is actively training for races. – editor
I have been working like a maniac and nonstop since I arrived in Italy for my bike touring job at the end of August. However, I am feeling good and recovering well and happy to to move forward for next year in training. I am starting to really look forward to getting in some hard solid winter training now and especially being in Tucson will be amazing!! I can't wait to get back into my regular training regime. On another note, I've recorded some observations during my time in Italy about my nutrition and vitamins.
"As I am now at the beginning of my touring/working season Iâ€™d like to use this time as my sort of off for supplements. From vitamins, as I have found in the past that I have trouble staying on schedule and taking them while working. I feel that my nutrition is still adequate as I eat vegetables and meat and other necessary things for the amount of effort and activity I am putting my body through. But I also know I will feel the difference without a constant flow of vitamins and supplements from integrated health."
"Now that I am in my moment of break and Iâ€™ve been working constantly for about a month, I must stay that I have also not been taking vitamins for a couple weeks and I can definitely feel the difference. Especially in my diet when I am not eating as healthy (as I do when training) or being as consistent with consuming vegetables.
I notice a lack of energy when I am working and lack of intensity on the bike when I'm riding. This is fine for now, and a good test for me as during this time I do not need a high-intensity effort while riding and it is a good test of my energy levels to see the contrast while I'm working compared to training.
I will begin taking some supplements again regularly which I think will help and will also demonstrate the necessity to have a regular schedule of nutritional supplements even when my work and travel schedule is so busy."
"Boy do I feel the difference! Since I have been regularly taking supplements again I can feel my energy going up and my willingness to push more and have more intensity on the bike. I feel the difference in my regular diet as well as I feel more motivated to eat healthy. This is a big contrast and difference I can see from the period when I was taking supplements to when I stopped and now again to taking them. This shows how big the influence of nutritional supplementation is for my body.
I will continue taking my vitamins and being active while working and also eating a healthy diet to maintain my energy levels and physical ability. I am so busy while working that supplements are often hard to take while changing hotels or setting things up for the day. But if I have my vitamin bag and make sure to keep it somewhere easily accessible, then I am more willing to take them and can easily.
It is great to be working so closely with an amazing company like Health Products Distributors where I can do this sort of test to see the differences. It shows a huge difference in their products compared to just food and how they affect my body. I have been taking Mighty Multi-Vite!, Ultimate Protector, Omega Plus, and Myo-Mag.
The supplements are amazing and I LOVE them and again I cannot wait to return to my competitive training this winter in Tucson." ~
Editor's notes: Irena primarily takes HPDI Foundational Supplements which are the base or core of a nutritional supplement program. Foundational supplements include a high-potency multivitamin (Hank & Brian's Mighty Multi-Vite!), vitamin C/antioxidant formulas (Ultimate Protector Nrf2 activator formula), essential fats (Omega Plus), and Rejuvenate! high-RNA superfoods (Rejuvenate! PLUS and Rejuvenate! Berries & Herbs). She also takes other HPDI formulas like Myo-Mag (magnesium formula), pH Adjust alkalinizing formula, Warrior Mist (topical pain reliever). and other formulas depending on her needs.
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INTRODUCING THE MICROBIOME
For centuries, scientists have recognized a limited number of pathogenic bacteria for which antibiotic therapies have become the mainstream treatment. However, advanced DNA sequencing techniques coupled with data revealed from the Human Genome Project have made it possible to study a vast world of ‘germs’ – both pathogenic and beneficial – that dwarf our previous knowledge.
While we inherit more than 22,000 genes from our parents, the bacteria that exist in and on our bodies contain at least eight million bacterial genes which amounts to 360 times more bacterial genes than human genes! The genetic material from bacteria that populate the human body is known as the human microbiome.
Your microbiome is likely similar to that of your immediate family, as we naturally inherit our family’s microbiota. Through the course of our lives, we pick up other bacteria from food, water, and other parts of our environment. Scientists estimate we each carry 100 trillion bacteria in our intestinal tract alone!
In this teeming landscape of bacteria, both you and the bacterial communities derive benefit. Many researchers use the term "mutually beneficial" when describing the evolving bacterial communities in our gut.
THE BALANCE OF BACTERIA AND YOUR HEALTH
In 2010, the Human Microbiome Project published an analysis of 178 genomes from bacteria that live in or on the human body. 10,000 different types of bacteria in the human body have been identified, including novel genes and proteins that serve functions in human health and disease. The vast numbers of bacteria discovered appear to provide benefit to the human body, not harm.
Martin J. Blaser, chairman of the Department of Medicine and a professor of microbiology at the New York University (NYU) School of Medicine states: "Germs make us sick, but everyone focuses on the harm. It’s not that simple, because without most of these organisms we could never survive."
As scientists map the human microbiome, they are beginning to understand the difference between normal and abnormal. Proper bacterial balance is vital to healthy immune function, providing appropriate protection against potential infections, playing a critical role in the digestion and absorption of food and nutrients, and even regulating mood. The interaction of multiple strains of bacteria is an essential element in health and wellbeing.
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Evidence supports the concept that microbiota balance can have a large impact on healthy metabolic processes. This delicate balance has a definite impact on nutrient acquisition and overall energy regulation.
The impact of the gut microbiota is far reaching in the body. Continued investigation into the microbiome will yield powerful data, enabling the development of novel options to support healthy mood, metabolism, signaling molecules and much more.
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Supports immune health
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WHY SOIL-BASED ORGANISMS?
Through diet and lifestyle, our earliest ancestors were routinely exposed to spore-based bacteria found in healthy soils and our natural environment. In our modern and hyper-sanitized world, this primitive yet vital connection to nature has been all but lost.
Soil-based organisms (SBOs) define a class of probiotic supplements based on a greater understanding of the incredible diversity of the human gut, coupled with a deeper appreciation for how humans and their commensal “helper” bacteria work together to produce a healthy system.
Soil-based bacteria have a three-stage life cycle, with each stage triggered by nutrient availability: vegetative growth, sporulation, and germination. The sporulation phase is particularly relevant to its potential as a probiotic. The spore structure preserves the bacteria in a dormant phase and against any harm whether in any terrestrial environment or in the acidic environments of the stomach and upper intestines. When these probiotic microbiota are ingested, they travel all the way to the lower intestine where they come alive. Like a seed, warm temperatures, moisture, and nutrients stimulate the germination stage where bacteria emerges from dormancy. Soil-based probiotics are well-adapted to the environment of the gut, and have been shown to remain in the digestive tract where they can provide long term benefit.
SBO probiotics are characterized by two traits that make them superior to other probiotics: 1) the spore phase enabling natural resistance to the harsh environment of the upper digestive tract and stomach, and 2) inherent environmental stability that does not require the addition of specialized coatings or preservatives to ensure a clinically relevant amount reaches the appropriate areas of the gut.
Though SBO probiotics are based directly on symbiotic communities of bacteria found in natural soil environments, these organisms are not harvested directly from the earth to be packaged as a supplement. They are instead produced in a safe, monitored environment to ensure specificity of the strains.
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MULTI-STRAIN BACILLUS COMPLEX
Bacteria are incredibly ubiquitous, highly adaptable ancient life forms that evolved relatively unchanged over nearly 4 billion years. Bacillus, in particular, is likely Earth’s most resilient bacteria―the oldest of which having been cultured and identified from the abdominal contents of extinct bees preserved in amber for 25 to 40 million years.
Through diet and lifestyle, our earliest ancestors were routinely exposed to bacillus spores found in healthy soils and our natural environment. Yet we no longer have routine exposure to bacillus spores due to the hyper-sanitization of our post-industrial civilization. Terraflora’s unique probiotic + prebiotic bio-complex of commensal bacillus strains reconnect humans with their ancestral environment.
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In addition to our proprietary new RibosporeTM (Bacillus pumilus) and Bacillus Megaterium EM144TM—Bacillus subtilis, Bacillus clausii, and Bacillus coagulans complete Terraflora’s multi-strain probiotic bio-complex.
ADVANCED PREBIOTIC BIO-COMPLEX
Terraflora™ contains a prebiotic blend of certified organic, wild-harvested seaweeds, mushroom extracts, and humic acid. These ancient, food-based prebiotics support commensal microbiota with a diverse spectrum of naturally-occurring polyphenols and polysaccharides designed to strengthen healthy intestinal flora. This bio-complex includes:
LARCH ARABINOGALACTAN: A solvent-free water extract that retains all bioactive polyphenolic flavonoids present in Larch, including taxifolin and quercetin. Larch arabinogalactan is a densely branched, non-starch polysaccharide consisting of galactose and arabinose molecules. It has been shown to increase production of critical short-chain fatty acids (SCFAs) such as butyrate in the gut. Butyrate is the principle fuel for intestinal cells and supports healthy tight junctions in the gut lining. In addition, Larch arabinogalactan enhances beneficial gut flora and increases levels of beneficial intestinal anaerobes, particularly Bifidobacterium longum.
FUCUS VESICULOSUS (BLADDERWRACK) & UNDARIA PINATIFIDA (WAKAME) EXTRACTS: These are certified organic solvent-free water extracts that are wild-harvested from clean ocean waters of Patagonia and Nova Scotia. They are rich in marine polyphenols and complex, sulfated, fucose-rich polysaccharides called fucoidans. Fucoidans are found in edible brown seaweeds and are shown to have multiple bioactivities including the support of healthy inflammation response in the GI tract. In vitro studies show that fucoidan effectively inhibits adhesion of pathogenic bacteria Helicobacter pylori and Escherichia coli to human cells. Furthermore, they increase the abundance of beneficial bacteria and significantly decrease inflammatory response and antigen load of the gut microbiota. In addition, they may also help maintain levels of beneficial bacteria in the gut during antibiotic use and are also known to increases the integrity of tight junctions in the gut lining.
NORDIC CHAGA EXTRACT: This ingredient is a certified organic hot-water extract obtained exclusively from the mushroom fruiting body. It is sustainably wild-harvested in the Arctic (Finnish Lapland forest) and contains a diverse spectrum of polysaccharides and polyphenols. This extract has been shown to help protect against acute colonic inflammation and shown to decrease the Firmicutes-to-Bacteroidetes bacterial ratios. Decreased Firmicutes-to-Bacteroidetes ratios are significantly associated with lower body mass index (BMI).
RED REISHI EXTRACT: A certified organic extract obtained by traditional hot-water extraction methods exclusively from the mushroom fruiting body. It contains a diverse spectrum of polysaccharides and polyphenols that have been shown to increase microbiota richness and regulate intestinal barrier function. It is known to support the health of the gut lumen. Furthermore, is has been shown to decrease Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels.
HUMIC ACID: The humic acid in Terraflora™ is water extracted from ancient freshwater humate deposits. It has been shown to significantly increase the overall concentration of colonic microbiota.
Abstract Mushrooms have long been used for medicinal and food purposes for over a thousand years, but a complete elucidation of the health-promoting properties of mushrooms through regulating gut microbiota has not yet been fully exploited. Mushrooms comprise a vast, and yet largely untapped, source of powerful new pharmaceutical substances. Mushrooms have been used in health care for treating simple and common diseases, like skin diseases and pandemic diseases like AIDS. This review is aimed at accumulating the health-promoting benefits of edible mushrooms through gut microbiota. Mushrooms are proven to possess anti-allergic, anti-cholesterol, anti-tumor, and anti-cancer properties. Mushrooms are rich in carbohydrates, like chitin, hemicellulose, β and α-glucans, mannans, xylans, and galactans, which make them the right choice for prebiotics. Mushrooms act as a prebiotics to stimulate the growth of gut microbiota, conferring health benefits to the host. In the present review, we have summarized the beneficial activities of various mushrooms on gut microbiota via the inhibition of exogenous pathogens and, thus, improving the host health.
The marine environment is an untapped source of bioactive compounds. Specifically, marine macroalgae (seaweeds) are rich in polysaccharides that could potentially be exploited as prebiotic functional ingredients for both human and animal health applications. Prebiotics are non-digestible, selectively fermented compounds that stimulate the growth and/or activity of beneficial gut microbiota which, in turn, confer health benefits on the host. This review will introduce the concept and potential applications of prebiotics, followed by an outline of the chemistry of seaweed polysaccharides. Their potential for use as prebiotics for both humans and animals will be highlighted by reviewing data from both in vitro and in vivo studies conducted to date.
Abstract AIM: To test the effects of humic acids on innate microbial communities of the colon. METHODS: We followed the effects of oral supplementation with humic acids (Activomin®) on concentrations and composition of colonic microbiome in 14 healthy volunteers for 45 d. 3 × 800 mg Activomin® were taken orally for 10 d followed by 3 × 400 mg for 35 d. Colonic microbiota were investigated using multicolor fluorescence in situ hybridization (FISH) of Carnoy fixated and paraffin embedded stool cylinders. Two stool samples were collected a week prior to therapy and one stool sample on days 10, 31 and 45. Forty-one FISH probes representing different bacterial groups were used. RESULTS: The sum concentration of colonic microbiota increased from 20% at day 10 to 30% by day 31 and remained stable until day 45 (32%) of humic acid supplementation (P < 0.001). The increase in the concentrations in each person was due to growth of preexisting groups. The individual microbial profile of the patients remained unchanged. Similarly, the bacterial diversity remained stable. Concentrations of 24 of the 35 substantial groups increased from 20% to 96%. Two bacterial groups detected with Bac303 (Bacteroides) and Myc657 (mycolic acid-containing Actinomycetes) FISH probes decreased (P > 0.05). The others remained unaffected. Bacterial groups with initially marginal concentrations (< 0.1 × 109/mL) demonstrated no response to humic acids. The concentrations of pioneer groups of Bifidobacteriaceae, Enterobacteriaceae and Clostridium difficile increased but the observed differences were statistically not significant. CONCLUSION: Humic acids have a profound effect on healthy colonic microbiome and may be potentially interesting substances for the development of drugs that control the innate colonic microbiome.
Warrior Mist™ is the most effective formula for pain relief offered by HPDI. Warrior Mist is an all-natural, fast-acting, topical pain reliever that is effective for many types of pain. I should know. I have used it nearly every day—for years!
Types of pain Warrior Mist is known to stop, reduce, or soothe include: back pain (including sciatica), knee pain, carpal tunnel syndrome, headaches (including migraines), neck pain and tension, stiff and painful (or pulled) muscles, plantar fascitis, arthritis, sports injuries, old injuries, sprains and strains, bruises (including deep bruises), shin splints, tennis elbow, nerve pain, and post surgery pain.
Practicing aikido for years, I have a frequent need for the rapid effects of Warrior Mist. Having used it for regularly for a long time, I appreciate how quickly it relieves pain like joint pain or sprains. It also works spectacularly for bruises, cuts, abrasions, burns, bug bites, and many other applications.
TESTIMONIAL: "This really works. I had tried several other products, including prescription medications, and little success. There was a noticeable difference after my first use of the product." – Amazon customer
Warrior Mist comes in a convenient one-ounce spray bottle. I shake the bottle and then add a few pumps—or as many as I need—to my non-pumping hand and rub onto the affected area. You can also spray it directly onto skin before rubbing it in with a clean hand. If you need more, you can always unscrew the cap and pour directly into your hand or onto skin, but I usually only reserve this action for times when I'm at the end of the bottle and I want to use all the Warrior Mist remaining in the bottle.
The small bottle travels well, and I usually take it with me whenever I travel. I also keep a bottle ready in a small hiking kit that I carry with me on the trail. While I may not always need it, nevertheless it is there. I cannot count how often I used it when I've least expected to need it. Sprained ankles or swollen fingers heal a lot faster than you might expect, compared to not having Warrior Mist around. It even works well on things like mosquito bites—and helps repel them.
Warrior Mist can be combined effectively with other natural topical products, especially Ancient Minerals Magnesium Oil (see video). I often mix a little Warrior Mist with Magnesium Oil in my palm. This mix gives me all the benefits of Warrior Mist with the added boost of extra magnesium chloride that speeds healing.
WARRIOR MIST BENEFITS
Warrior Mist offers rapid pain relief and many other benefits:
• RAPID, EFFECTIVE PAIN RELIEF – Formulated as a fast-acting pain reliever using only natural ingredients
• LONG LASTING – pain relief last eight hours (or more) per use. This is a natural formula, so you will eventually need to re-apply it. But fewer applications means more time living life pain free.
• SAFE – 100% natural formula. This means that unlike prescription drugs or many over-the-counter medicines, there are no harsh or dangerous side effects.
• RAPID HEALING. Not only effectively relieves pain, but also supports rapid healing at the cellular level. It thereby supports healing at the sources of pain. i.e., helps with the underlying causes of pain.
• REDUCES MUSCLE SORENESS AND TENSION. Another benefit of direct topical application of natural, yet powerful (mostly herbal) ingredients. While this has obvious benefits for athletes,it also helps weekend warriors, or anyone who has muscle soreness due to any reason!
• INCREASES CIRCULATION. Increased circulation is a significant healthy benefit in itself, allowing better oxygenation of tissues, supporting healing, reducing stagnation of blood, and boosting processes of detoxification.
• LESSENS INFLAMMATION. Inflamatory processes can be harmful to the body. Warrior Mist helps reduce inflammation naturally, and thereby lessens free-radical damage from it, for example. This significantly supports your healing process.
• TISSUE REPAIR. When the ingredients in Warrior Mist penetrate tissues, then those tissues can begin the process of healing and repair, and do it faster!
• HEALS SKIN IRRITATIONS. A major added benefit is the healing of "minor" skin irritations, cuts, abrasions, etc. This is because the ingredients in Warrior Mist™ do double duty as superb nutrients for the skin.
• SCAR REDUCTION. Warrior Mist™ can soften scar tissues and stimulate the kind of deep healing that results in smaller scars and improved appearance of scars.
TESTIMONIAL: "Warrior Mist is the only product that I have found which truly relieves the osteoarthritis pain in my knee!! I am amazed by the speed and effectiveness of Warrior Mist. As an older person who has planned and worked to be able to complete my life in my own home, Warrior Mist contributes enormously to my ability to do that! Thank you for this excellent product!" – Amazon customer
WHY IS WARRIOR MIST EFFECTIVE?
Warrior Mist™ is a revolutionary skin, muscle, and joint support formula that uses DMSO, olive oil, coconut oil, and water as base (or carrier) ingredients that transdermally transport the other ingredients directly to the site of the problem where they work together harmoniously and effectively.
Functional ingredients carried to the site of pain include: peppermint oil (the primary source of menthol in the product), magnesium chloride, MSM, lemon oil, and lavender oil. Each of the functional ingredients (and their amounts) were carefully selected for their ability to stop pain, to help the body overcome the causes of pain, to promote healing at the local level, or to work synergistically with the other ingredients. Warrior Mist is 100% all-natural and totally safe!
As a topical analgesic, Warrior Mist conforms to the proposed rules set forth in FDA Monograph 348. The label used on the current Warrior Mist (1 oz spray bottle) meets the requirements set forth in this monograph. Even though there are a number of ingredients in Warrior Mist that can potentially provide temporary pain relief, the FDA monograph only recognizes the ingredient menthol, the major ingredient in peppermint oil, as an allowable active ingredient. According to the monograph, we can only mention menthol as the active ingredient and all other ingredients must be labelled as inactive ingredients.
The truth is that all the ingredients (functional and base/carrier ingredients) add up to a synergistic formula that rapidly relieves pain in a single, easy-to-apply topical product. What more could you ask for?
Dimethyl sulfoxide (DMSO), a by-product of the wood industry, has been in use as a commercial solvent since 1953. Furthermore, in 125 countries throughout the world doctors prescribe it for a variety of issues, including inflammation. DMSO has been used widely as a carrier in topical analgesic formulas. Laboratory studies have shown that DMSO is able to block peripheral nerve C fibers.
Burns, cuts, and sprains have been treated with DMSO. Relief is reported to be almost immediate, lasting up to 6 hours. DMSO reduces inflammation by several mechanisms. It is an antioxidant, a scavenger of the free radicals that gather at the site of injury. Studies have shown DMSO to be one of the safest ingredients known with a toxicity similar to that of water.
DMSO has long been used to promote healing both in animals and humans. Those who have used it for minor cuts and burns report that recovery is speedy. Several studies have documented DMSO use with soft tissue damage, local tissue death, skin ulcers, and burns. Applied topically and repeatedly, DMSO flattens the raised, nodular, lobed liner mass of scar tissue in keloids and acne.
MSM is a naturally occurring nutrient found in normal human diets. In the body DMSO and MSM, which form each other, are indistinguishable in their biochemical effects. They reach a equilibrium distribution between them that is dependent on the local body chemistry, and is independent of which one you start with. The metabolic enhancement mechanism of MSM and DMSO is that of an exceptionally effective oxygen transport system. This system is made particularly effective by the feature that both DMSO and MSM are highly soluble in both oil and water.
MSM makes cell walls permeable, allowing water and nutrients to freely flow into cells and allowing wastes and toxins to properly flow out. The body uses MSM along with Vitamin C to create new healthy cells, and MSM provides the flexible bond between the cells. Without proper levels of MSM, our bodies are unable to build healthy cells, and this leads to problems such as lost flexibility, scar tissue, wrinkles, varicose veins, hardened arteries, damaged lung tissues, dry cracking skin, digestive disorders, joint problems, and inability to defend against allergic reactions to food, animals and plants.
The applications of MSM include pain control (analgesic), inflammation control, dilation of blood vessels, increased blood flow, reduced muscle spasm, altering the crosslinking process in collagen (e.g., reducing scar tissue,) anti-parasitic effects (particularly against Giardia), and immune normalizing effects. MSM has a unique ability to pass through cellular membranes (including skin).
The primary constituent of peppermint oil is menthol, which causes a physical reaction when inhaled or applied to the skin. Menthol produces an immediate and pronounced sensation of coolness that effects the body quite noticeably, and creates a "warming effect" as blood flows into the area of application.
Peppermint oil can be used externally for providing relief from pain. Peppermint oil increases your immunity. It also improves blood circulation. Additional of the uses of peppermint oil include:acne, asthma, colds, cramps, dermatitis, exhaustion, influenza, headache, insect bites, mental fatigue, migraine, nausea, nerve pain, neuralgia, poor circulation, and respiratory disorders.
Lavender oil helps in treating migraines, headaches, anxiety, depression, nervous tension and emotional stress. The refreshing aroma removes nervous exhaustion and restlessness and increases mental activity. Because it induces sleep, it is often recommended for insomnia. Lavender oil is also an excellent remedy for various types of pains including those caused by sore muscles, tense muscles, muscular aches, rheumatism, sprains, backache,and lumbago. A regular massage with lavender oil can provide relief from pain in the joints.
Lavender oil is also good for improving blood circulation in the body. The health benefits of lavender oil for the skin can be attributed to its antiseptic and antifungal properties. It is used to treat various skin conditions, including acne, wrinkles, psoriasis, and other inflammatory conditions. It heals wounds, cuts, burns, and sunburns rapidly because it aids in the formation of scar tissues. It is also effective against insect bites. The oil also repels mosquitoes and moths.
Lemon oil is powerfully astringent and antiseptic. Lemon oil is detoxifying and is therefore good for blemishes associated with oily skin. Lemon oil is a powerful antioxidant and is a tonic for supporting the nervous and sympathetic nervous system. It's been long known that lemon oil is anti-infective, antibacterial (especially with spores), and antiviral. It can function as a disinfectant and exerts vitamin P-like action for improving microcirculation, promotes white blood cell formation, and improves immune function. It has also been widely used in skin care to cleanse skin and reduce wrinkles.
Magnesium chloride applied to the skin is an effective means for increasing magnesium levels in the body, and is particularly useful for relieving sore muscles and joints, and reducing pain related to functional magnesium deficiency. It is also proven for use in helping to calm “nerves” and reduce systemic bodily stress. Because the magnesium targets muscle tissues, it is thereby especially useful for replenishing depleted soft tissues and helping restore proper function.
Magnesium is necessary for the production of energy in the body. When the body receives adequate amounts of magnesium, it can produce the levels of energy required to sustain the body and enable it to thrive. Magnesium chloride is proven for use in a variety of general applications, including bruises, cramps, muscle tension, and migraine headaches.
Used as a base and mixed with other essential oils, olive oil makes a wonderful oil for skin health. In fact, it has been touted as one of the oldest healing and beauty techniques. A biblical reference from about 493 BCE documents the daily massage with olive oil and other oils as a part of the beauty regimen.
Coconut oil is a superb skin lotion because it both nourishes skin and is naturally anti-bacterial, antiviral, and antifungal due to its high content of medium chain triglycerides
DIRECTIONS: Shake bottle before applying. Wash hands before and after use. Apply in a thin layer to a clean, dry, and lotion-free area needing support. Shave thick hair that may prevent absorption by the skin. Gently massage the area of application to assist absorption. Reapply as needed 3–4 times daily. Contains DMSO, a known solvent. Use on people or pets at your own discretion.
USES: Warrior Mist™ is an all-natural skin, muscle, and joint support formula.
WARNINGS: For external use only. May cause temporary (up to 45 minutes) skin irritation, heating, or flushing upon use. Discontinue use if temporary skin conditions persist. Do not use on wounds or severely damaged skin. Do not bandage tightly. Avoid contact with eyes. Flush eyes with cool water if exposed. Do not use if allergic to any ingredients. Stop use and visit a health care professional if reason for use continues for more than one week. If swallowed get medical help or call a Poison Control Center. Consult a health care professional before use if pregnant.
Warrior Mist topical formula is highly effective for pain relief. A major advantage is that it is a natural formula (available without a prescription) and can safely be re-applied whenever necessary. Another benefit is that it lacks the side effects common to prescription pain medications.
Try Warrior Mist for yourself. If you're like me, you will want to keep a bottle or two ready for the aches and pains of daily life. Use it as often as you need it. Be a warrior!
Almost daily articles, reports, or studies appear claiming nutritional supplements are not effective. The claims vary, but the verdict is always there is little or no scientific evidence proving supplements (or the nutrients in supplements) work. Others assert that people who take supplements have the world's most expensive urine. This is nonsense! The scientific evidence is clear, available, and it has been for a long time.
Among the many problems with these reports is bashing supplements based on studies using low dose or non-therapeutic levels of nutrients. There is frequently failure to consider the importance of synergy among nutrients. Often there is data manipulation via statistical methods (often in meta-analyses).
Well beyond the question of whether supplements support health are the factors in modern life that create a greater needs for supplementing with important vitamins, minerals, cofactors, and other nutrients.
This month we present "Seven Arguments for Nutritional Supplements." As the title implies, there are at least seven solid arguments for nutritional supplementation. There are actually a lot more.
To preview these arguments in favor of taking supplements, they are: 1) reduced food quality, 2) nutrient density varies by location, 3) modern lifestyles and stress, 4) environmental pollution, 5) too low RDAs, and 6) promotion of health and delaying of aging, and 7) the human right to correct information.
Essential Fatty Acids (EFA) are one type of essential nutrient required for health.
We at HPDI re-publish articles from the Orthomolecular News Service (OMNS) because the authors provide much needed truth. Truth the form of correcting the false assumptions of anti-supplement propagandists to clarify the benefits of nutritional supplements. This information can help people be healthier easily and at relatively low cost.
HPDI offers a full line of foundational nutritional supplements, including multivitamins, vitamin C and antioxidant formulas, essential fats, and high-RNA Rejuvenate! superfoods. We also offer nearly 100 other nutritional supplements from single nutrients to condition specific formulas. See our full product overview.
Enjoy this article from the Orthomolecular News Service (OMNS). ~
Seven Arguments for Taking Nutritional Supplements
by Dag Viljen Poleszynski, PhD
(OMNS Sept 12 2018)
One of the most vitamin-restrictive countries in the world is Norway. There, authorities limit potencies to only slightly higher than RDA (Recommended Dietary Allowance) levels for dietary supplements sold outside of pharmacies. The traditional reasoning is that most people receive the nutrients they need from a "balanced diet." 
The authorities are also obsessively concerned that some vitamins and minerals are harmful in high doses. And, since an intake of water-soluble vitamins in excess of needs is excreted in the urine, Norwegian "experts" advise that taking supplements is a waste of money.
Accordingly, the argument goes, the public should be protected not only from possible harm, but also from wasting money on unnecessary nutrients. The official policies on nutritional supplements vary within OECD (Organization for Economic Cooperation and Development) countries. Some are more liberal, while others are even more restrictive.
The official view on the connection between nutrient intake and possible toxicity is illustrated by the Norwegian Food Authority in a graph. 
Perceived risk from intake of nutrients. (Source: Expert Group on Vitamins and Minerals. Safe upper limits for Vitamins and Minerals. May 2003: Food Standards Agency, UK.)
The graph illustrates the official view on nutrients, assuming that nutrients function in the same way as pharmaceuticals, which they do not. Supplements of most vitamins, but also minerals and other nutrients, do not have very serious side effects even when taken at very high levels - in contrast with most drugs. [3,4] The fact that most of the chemotherapeutic drugs used against cancer have none or even just marginal effects against most cancers , while at the same time cause a lot of serious side effects, is rarely up for discussion.
The idea that nutritional supplements are not safe has a legal underpinning in Norwegian Food Law, which in section 16 prohibits sale of any food which is not safe: "Any food shall be considered not to be safe if it is seen as detrimental to health or not fit for consumption." 
However, the Norwegian authorities do admit that vitamin D supplements are needed during part of the year.  Only part of the year? One third of Norway is within the Arctic Circle. Norway has far too little sunshine (especially during winter months) to get adequate levels of vitamin D from UVB radiation on the skin.
The authorities also recommend that pregnant women take folic acid to prevent birth defects, and omega-3-fatty acids may be advisable for those who do not eat fish regularly. Norwegians have a long tradition of giving children cod liver oil, which in a daily tablespoon provides enough vitamin A and D and essential fatty acids to cover basic needs.
Essential and conditionally essential nutrients
There are thousands of dietary supplements on the market, including 40+ essential nutrients alone and in various combinations, i.e. vitamins, minerals, trace elements and fatty acids. However, a number of other nutrients are "conditionally essential", meaning that the body normally can make these molecules, but some people do not make optimal amounts. Examples are L-carnitine, alpha-lipoic acid, the methyl donor betaine,  chondroitin sulfate, coenzyme Q10, choline, amino acids such as tyrosine or arginine, and "essential" sugars normally formed in the body. 
Healthy young people normally make sufficient amounts of conditionally essential molecules in the body, although the levels are not always optimal. With inadequate levels of minerals or vitamins, key enzymes in biochemical pathways may not function optimally.
Due to genetic mutations, some enzymes may have increased needs for certain cofactors (vitamins), which can prevent them from functioning optimally. Some enzymes only function normally when supplied with cofactors in greater amounts than normally required.
If supplements of essential nutrients prove insufficient for optimal enzyme function, "conditionally essential" nutrients may be added as part of a comprehensive, therapeutic program.
Parents are advised to become familiar with the literature on essential nutrients, for instance by consulting the Orthomolecular News Service. Children should be given supplements in appropriate doses and in a suitable form. Pills should not be given before children can control the swallowing reflex. Multivitamin powder can be given dissolved in water or juice. Parents should not dose vitamin C so high that a child comes to school or kindergarten with loose bowels or diarrhea.
In high doses, niacin may cause unpleasant side effects such as flushing and itching lasting up to several hours.  Although this is not dangerous, it may cause a child to feel unwell and anxious. Starting niacin supplementation with a low dose and gradually increasing it will allow the body to adapt and avoid the niacin flush.
A multivitamin supplement containing moderate amounts of niacin is often adequate until a child is 8-10 years old. For younger children, the dosage should start with only a few tens of milligrams, and not increased to more than 50-100 mg/day. Adults may gradually get used to taking 1,000-1,500 mg/d divided into 3 doses per day.
When it comes to omega-3 fatty acids (omega = ω) such as EPA and DHA, children may be given cod liver oil and served fish and/or other seafood 2-3 times a week. It is important to check the dose of vitamin A supplied, as it can be toxic in high doses, especially for children. One problem with cod liver oil today is that vitamin D has been removed during processing, thus changing the natural ratio of the two vitamins so that we ingest relatively too much of vitamin A. 
Higher dosages may be given after having consulted a therapist who has measured the ratio of omega-6 to omega-3 fatty acids in relevant cell membranes (red blood cells). In most industrialized countries, many people get too much of the omega-6 fatty acids, and would therefore benefit from eating more seafood or taking supplements with omega-3 fatty acids derived from organisms low in the food chain (algae, krill).
Flax seeds contain a high level of the essential omega-3 fatty acid alpha-linolenic acid, and freshly ground flaxseed meal or flax oil can be mixed with breakfast cereals or smoothies. Note that it may be advisable to limit eating farmed fish to once per week, since their fodder contains less omega-3 fatty acids than the food eaten by wild fish, and possibly also contains more contaminants.  Some researchers even warn against letting children eat too much fish because of the content of environmental toxins. [13,14]
Reasons for high-dose supplements of micronutrients
I have identified a number of arguments in favor of supplementing the modern diet with essential nutrients, here summarized with seven headlines. Most people should consider taking a multivitamin supplement containing vitamins and minerals even if they eat a nutritionally balanced diet.
Additional nutrients may contribute to better health and, in some cases, can be of vital importance in our modern world. The arguments are presented in random order, i.e. the order does not reflect priority.
1. The agricultural revolution has reduced food quality
The transition from an existence as hunter and gatherers to urban agriculture around 10,000 years ago began an epoch when foods were mass-produced but had lower nutritional density, compared with the previous food eaten by our ancestors. The nutritional density in many foods has fallen significantly since human societies transformed from hunter-gatherers into resident farmers. This is especially true in the last 60-70 years after agriculture was changed from small, versatile ecologically driven family farms to large, chemical-based, industrial agriculture. 
The reduction of nutritional content in modern crops, compared with older varieties, is well documented.  It is a consequence of soil erosion, loss of essential minerals from continual heavy use, combined with breeding of new varieties, which has increased the size and growth rate of plants by increasing the content of sugar and water and decreasing their mineral content compared to ancient species. At the same time, the relative content of other macronutrients (fat, protein/amino acids) and antioxidants may have been reduced.
Reduced nutritional density in many foods, combined with the use of refined "foods" like sugar, white flour and refined oils, places a greater priority on eating the most nutritious foods.
Farm produce grown organically generally has higher levels of essential nutrients such as trace minerals because the soil contains higher levels of trace minerals and the produce grows slower and thus has more time to absorb nutrients from the soil. Examples of nutrient dense foods are sardines, wild salmon, shellfish, eggs, liver, kale, collards and spinach, sea plants (seaweed), garlic, blueberries, and dark chocolate. 
2. Nutritional content of food varies with geographical location
Nutritional density varies considerably geographically between different regions, even with the same agricultural methods. This was documented in the United States in 1948 by a researcher at Rutgers University in the so-called Firman Bear report.  At that time agriculture was little mechanized, and artificial fertilizers and pesticides were hardly used.
The analysis found large differences in the content of minerals in the same food. The largest variations were found for potassium, sodium, boron and iron in spinach, while the greatest differences in calcium, magnesium and copper content were found in tomatoes.
The soil in areas with relatively low rainfall may in some cases contain an extremely high concentration of minerals, which is reflected in the plants growing there. This was well documented 70 years ago in the book Tomorrow's Food.  The dentist George W. Heard found that the soil in Hereford, Texas, was exceptionally rich in minerals.
Hereford became known as the "town without a toothache" after a newspaper article from January 29, 1942, reported that Hereford had the lowest incidence of tooth decay of any city in the United States.  Dr. Heard found that people in Hereford had exceptionally few dental cavities and also that the soil locally was especially rich in minerals. He emphasized that the population in the county ate unprocessed food and was drinking raw milk. 
Recent research shows that differences in the content of the selenium in the soil can cause major differences in the concentration of selenium in meat.  For instance, since the soil in Finland is poor in selenium, the authorities decided in the early 1980s to add selenate to commercial fertilizers. A survey of selenium status among 108 healthy young people showed an increase in the blood selenium level of about 50 percent after four years. 
A similar problem with the level of minerals in the soil exists for the content of magnesium. Often when the soil gets depleted of magnesium from heavy use, this essential mineral is not included in soil amendment with fertilizers. Produce grown in soil with an adequate level of magnesium will contain more magnesium than produce grown in soil deficient in magnesium.
Perhaps as many as 70-80% of the US population is magnesium-deficient, which causes many health problems.  Magnesium supplements (chloride, malate or citrate) can provide an adequate level when vegetables grown in soil with adequate magnesium are not available.
3. Stress and the modern lifestyle increase the need for nutrients
Mental stress increases the excretion and hence the need for many nutrients. Among the most important are magnesium and vitamin C, both of which are used by the body in larger quantities during periods of physical and mental stress. [24,25] Compared with our past as hunters and gatherers, today´s stress is often of a more permanent nature. Instead of experiencing occasional situations where we had to fight or flee, many of us live with recurring stress day in and out.
Vitamin C protects the brain and nervous system from damage caused by stress because the synthesis and maintenance of chemical neurotransmitters such as adrenaline and noradrenaline requires adequate levels of vitamin C. 
Vitamin C is also needed to repair collagen which is essential for skin, blood vessels, bones and joints, and muscles. When these are damaged by physical stress, extra vitamin C is necessary.
A controlled trial of 91 adults who experienced increased anxiety and stress 2-3 months after an earthquake in New Zealand in 2011 was divided into three groups, two were given a broad spectrum supplement of micronutrients in low or higher doses.  The supplements were found to alleviate the experience of stress, with the biggest dose having the biggest effect.
Our sedate, modern lifestyle reduces the need for energy from food, which implies a lower food intake or obesity. Loren Cordain, PhD, and coworkers have estimated that hunter-gatherers had significantly higher energy needs than the typical modern office worker. 
A lower energy intake generally reduces the absolute intake of all nutrients, while the need for some nutrients is not always reduced proportionally with energy intake. Overall this suggests that more exercise along with a more nutritious diet, including supplements of essential nutrients and less carbohydrates, will help to prevent obesity and maintain health.
Processing of food reduces its nutritional content, and the finished products are often based on fractions of the original foods. One example is milling grain to make white flour,  which has a lower nutritional density than whole grain flour.
The reduction in nutritional value has accelerated since whole foods are now divided into pieces, for example, boneless chicken breast. When meat is injected with saline to increase the volume, the relative level of essential nutrients is reduced. In the United States, many supermarkets in low-income rural and inner city areas have a limited selection of nutrient-dense foods, compared with high-income areas. 
4. Environmental pollutants increase the need for nutrients
The need for efficient detoxification and excretion is greatly increased by environmental pollution from the chemical industry, herbicides and pesticides used by industrial agriculture, antibiotic treatment of animals, transport, and plastic packaging. 
In our polluted world, the increased toxic load may be compensated for by an increase in nutrients to promote detoxification. One can respond by taking large doses of supplements of essential nutrients, for example, antioxidants vitamin C and E, and an adequate dose of selenium, which help the body detoxify harmful chemicals. Also helpful is regularly taking sauna baths, fasting periodically, and eating an excellent diet that includes generous portions of dark green leafy vegetables and colorful vegetables and fruits. 
A recent study predicts that global warming may reduce the nutrient density in many foods worldwide.  Atmospheric CO2 is estimated to surpass 550 ppm in the next 30-80 years, leading to larger crops with lower content of protein, iron and zinc per energy unit.
Assuming that diets remain constant, while excluding other climate impacts on food production, the researchers estimated that elevated CO2 could cause an additional 175 million people to be zinc deficient and an additional 122 million people to be protein deficient in 2050. Anemia would increase significantly if crops lose even a small amount of iron. The highest risk regions - South and Southeast Asia, Africa, and the Middle East - are especially vulnerable, since they do not have the means and access to compensate using nutritional supplements.
5. The RDA for essential nutrients is too low
The recommended nutrient reference intake (NRI) has been defined by UK authorities and the EU Food Safety Agency as the dose that is adequate for 95 percent of the population.  These authorities have given recommendations for a total of 41 chemical substances,  including 13 vitamins, 17 minerals/trace elements, 9 amino acids and two fatty acids. The problem with such guidelines is that when using the same 0.95 fraction for just 16 of the essential nutrients, the fraction of the overall population that has their needs met with the RDA is less than half (0.9516 = 0.44).
Given the above assumption, the proportion of the population having all nutrient needs met falls below 25 percent for 30 nutrients (0.9530 = 0.21). These 25 percent will not necessarily get optimal amounts, just enough so that they probably will have no deficiencies in accordance with established standards. Each individual is different and has different biochemical needs, so we all need different doses of essential nutrients. Many vitamins and minerals can give additional benefit when taken at higher doses.
The need for several essential nutrients increases with age and sickness. This applies, for example, to vitamin C, vitamin D, magnesium, and iron. In 2017 the Norwegian Food Safety Authority proposed to revise the official maximum levels for vitamins and minerals in dietary supplements. 
Their proposal introduced four different age categories with separate maximum intakes. Initially, the agencies proposed to revise the daily doses allowed in dietary supplements for folic acid, magnesium, calcium, vitamin C and D. At the same time, maximum rates were temporarily suspended for vitamins A, E, K, thiamine (B1), riboflavin (B2), niacin (B3), pantothenate (B5), pyridoxine (B6), cobalamine (B12), biotin, and for phosphorus, iron, copper, iodine, zinc, manganese, selenium, chromium, molybdenum, sodium, potassium, fluoride, chloride, boron and silicon.
The upper limits for some nutrients may be changed in the future. Unfortunately, Norwegian nutrition "experts" will likely continue to limit allowable doses below those freely available in the US and even Sweden.
6. An optimal nutrient intake promotes health and delays aging
A spokesperson for optimal nutritional intake is the well-known biochemist Bruce Ames, who proposed the "triage theory of nutrients," in which enzymes responsible for cell maintenance functions evolved to have lower affinity for the essential vitamin and mineral cofactors than the enzymes responsible for short-term survival, to preserve life during times of famine. 
Thus, higher levels of vitamins and minerals may delay mitochondrial aging, speed up the repair of large molecules such as DNA and collagen, and generally improve other cellular functions. This is an important rationale for taking higher doses of vitamins and minerals than recommended reference intakes.
Dietary supplements can slow the aging process, in part by reducing the harmful effects of free radicals, known to be involved in many diseases such as cardiovascular disease and cancer. 
Naturally occurring hormones and/or supplements of cofactors needed for optimal hormone production in the body can have a significant life-prolonging effect if the body produces less than optimal amounts.  This is especially relevant for those with a genetic predisposition for disease.
An optimum intake of all nutrients is difficult to achieve even for those who eat almost exclusively an excellent diet of nutrient dense foods, such as meat and innards, fish, shellfish, fowl, eggs, nuts, mushrooms, and vegetables, berries and nutritious fruits. Some nutrients such as folic acid or carotenoids in vegetables are absorbed better from processed than unprocessed foods.
Although vegetables are often considered to be a good source of vitamins, for example vitamin A from carrots, vitamin A is only found in animal products such as liver, egg yolk, fish cod and cod liver oil. Although eating raw vegetables is helpful for several reasons (vitamin C, fiber, microbiota), carotenoids (alpha/beta-carotene, lutein, lycopene) in vegetables are less well absorbed from raw than cooked food and better absorbed in the presence of added fat. [38,39].
Nutrients in vegetables are better absorbed when finely chewed, graded, or mashed , and cooking and grinding meat reduces the energy required to digest it  and increases nutrient absorption .
Orthomolecular pioneer Abram Hoffer and Orthomolecular News Service Editor Andrew W. Saul suggested this list of daily intakes of vitamins and minerals.  The Norwegian 2017 recommendations for adult men and women  are given in comparison. Individual needs may vary substantially from person to person and also with health status.
The figures for optimal intake are obtained from the Independent Vitamin Safety Review Panel of physicians, researchers and academics, who concluded:
"People are deceived in believing that they can get all the nutrients they need from a 'balanced diet' consisting of processed foods. To achieve an adequate intake of vitamins and minerals, a diet of unprocessed whole foods, along with intelligent use of dietary supplements is more than just a good idea: it is vital." [44: 55]
A well-known example is vitamin C, which can effectively fight viral infections, prevent or reverse disease caused by bacteria, and help the body detoxify organic and inorganic toxins.  Vitamin C also reduces the risk for cancer, strengthens connective tissues (collagen), and counteracts stress by increasing the adrenal´s production of cortisol. The dose required is set according to the body's need.
Nobel Price Laureate Linus Pauling suggested that an optimal daily intake of vitamin C could vary from at least 250 mg up to 20 grams per day.  Because unabsorbed vitamin C attracts water into the gut, some people may experience loose stools, gas and/or diarrhea by ingesting only 1-2 grams at a time, while others with a higher level of stress may tolerate 5-6 grams or more. The dose that causes loose stools is called the "bowel tolerance" for vitamin C.  To avoid the laxative effect of high doses, it is best to take vitamin C throughout the day in smaller divided doses.
When the body is stressed by disease, the gut will naturally absorb more vitamin C because the body needs more. To find the optimal dose, the intake should be increased until bowel tolerance is reached. Some people can tolerate more than 100,000 mg/d of vitamin C in divided doses during serious illness without having loose stool.
Liposomal vitamin C bypasses the normal bowel tolerance because it is absorbed directly through cell membranes, so higher doses can be tolerated without diarrhea.
7. A human right to receive correct information
Access to correct information about food and essential nutrients, including knowledge about the importance of food for health is a fundamental human right. Such information should not only provide a summary of the nutrient content of food, but in our opinion should also explain how dietary supplements can counteract deficiencies and prevent and reverse disease caused by nutrient deficiencies.
We should be free to purchase quality-controlled supplements of essential nutrients and to use them to counteract aging and damage from stress as part of a long-term health plan. The right to reject recommendations by doctors for symptomatic treatment with synthetic, some times life-threatening, drugs to alleviate symptoms should be included. [48,49]
I have not found any formulation of such rights from the Norwegian authorities. The role of parents and their right to receive correct health information is addressed in a book by lawyer Anne Kjersti C. Befring, a fellow at the University of Oslo since 2014. 
The use of dietary supplements is widespread. High doses of vitamins are thought to be helpful because they help the body recover from damage and maintain itself long-term. Many vitamins are not harmful in doses even 10 to 100-fold higher than officially recommended.
Some governments warn about possible negative side effects, even including increased mortality from "excessive" intake of certain supplements. However, supplements of essential nutrients have been available for more than 80 years. They are known to be safe, and the observed side effects are generally mild with few exceptions.
It is possible to ingest too much of certain vitamins and minerals (vitamin A, calcium, iron, copper, selenium) which may exacerbate an existing imbalance or lack of another mineral (magnesium, zinc). It is also important to balance intake of fatty acids in the omega-6 and omega-3 series, as most people get too much omega-6 and not enough omega-3.
Small children can be overdosed with adult doses of for example vitamin A or iron, and pills may be dangerous for babies or young children because they can get stuck in the throat. Therefore, I recommend consulting a doctor or nutritionist educated in orthomolecular medicine. Most people are likely to benefit from taking a broad-spectrum multivitamin/mineral supplement as a basic insurance against deficiencies.
Compared to pharmaceutical drugs, supplements of most essential nutrients are quite harmless. However, some supplements may have poor quality, or contain toxic metals such as lead or cadmium. Therefore, it is the duty of our authorities to ensure that potentially hazardous products or supplements of poor quality are not sold, and that consumers are offered fair prices in a free market.
An example where the Norwegian authorities do not follow up such basic duties is that pharmacies demand more than 1,600 Norwegian Kroner (about $190) per kg of vitamin C in powder form, which would cost less than $20 with free competition and no restrictions in permitted doses or outlets.
Those who want to use natural healing methods, such as the use of food and supplements of essential nutrients to prevent or reverse illness, should consult therapists who are qualified to give advice on how natural therapies can help.
I recommend that anyone interested in supplements read the references for this article as well as the archives of the Journal of Orthomolecular Medicine http://orthomolecular.org/library/jom/ and the Orthomolecular Medicine News Service http://orthomolecular.org/resources/omns/index.shtml . Both are free access online.
(Dag Viljen Poleszynski, PhD, is the editor of Helsemagasinet [Health Magazine] https://vof.no/arkiv/ . He has translated and published a large number of OMNS releases in Norwegian.)
1. National Nutrition Council. Dietary advice to promote public health and prevent chronic disease. Directorate of Health, Oslo January 2011.
22. Hintze KJ, Lardy GP, Marchello MJ, et al. Areas with high concentration of selenium in the soil and forage produce beef with enhanced concentrations of selenium. Journal of Agricultural and Food Chemistry 2001; 49: 1062-7. https://pubs.acs.org/doi/abs/10.1021/jf000699s
23. Mäkelä AL, Näntö V, Mäkela P, et al. The effect of nationwide selenium enrichment of fertilizers on selenium status of healthy Finnish medical students living in South Western Finland. Biological Trace Element Research 1993; 36: 151-7. https://link.springer.com/article/10.1007/BF02783174
24. Dean C. The Magnesium Miracle. Second Edition. New York: Ballantine Books, 2017. ISBN-13: 978-0399594441
25. Hickey S, Saul AW. Vitamin C: the real story. Laguna Beach, CA: Basic Health Publications, Inc., 2008. ISBN-13: 978-1591202233
26. Rucklidge JJ, Andridge R, Gorman B, et al. Shaken but unstirred? Effects of micronutrients on stress and trauma after an earthquake: RCT evidence comparing formulas and doses. Human Psychopharmacology and Clinical Experience 2012; 27: 440-54. https://onlinelibrary.wiley.com/doi/abs/10.1002/hup.2246
27. Cordain L, Gotshall RW, Eaton SB. Evolutionary aspects of exercise. In: Simopoulos AP, ed.: Nutrition and fitness: Evolutionary aspects. World Review of Nutrition and Diet 1997; 81: 49-60. https://www.ncbi.nlm.nih.gov/pubmed/9287503
28. Zenk SN, Powell LM, Rimkus L, et al. Relative and absolute availability of healthier food and beverage alternatives across communities in the United States. American Journal of Public Health 2014; 104: 2170-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202991/
29. Waldbott GL. Health effects of environmental pollutants. Second edition. St. Louis, MI: The C. V. Mosby Company, 1978. ISBN-13: 978-0801653308
36. Halliwell B, Gutteridge HMC. Free radicals in biology and medicine. 5th edition. Oxford, NY: Clarendon Press, 2015. ISBN-13: 978-0198717485
37. Hertoghe T. The hormone handbook. Copyright (c) 2006 Thierry Hertoghe. Surrey, UK: International Medical Publications, 2006.
38. Edwards AJ, Nguyen CH, You CS, et al. a- og ß-carotene from a commercial carrot puree are more bioavailable to humans than from boiled-mashed carrots, as determined using an extrinsic stable isotope reference method. Journal of Nutrition 2002; 132: 159-67. https://academic.oup.com/jn/article/132/2/159/4687130
39. Unlu NZ, Bohn T, Clinton SK et al. Carotenoid absorption from salad and salsa by humans is enhanced by the addition of avocado or avocado oil. The Journal of Nutrition 2005; 135: 431-6. https://www.ncbi.nlm.nih.gov/pubmed/15735074
40. Boback SM, Cox CL, Ott BD et al. Cooking and grinding reduces the cost of meat digestion. Comparative biochemistry and physiology. Part A, molecular & integrative physiology 2007; 148: 651-6. https://www.ncbi.nlm.nih.gov/pubmed/17827047
The peer-reviewed Orthomolecular Medicine News Service is a non-profit and non-commercial informational resource.
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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.