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AMAZING IMMUNE-ASSIST™ MUSHROOM FORMULA

Dr. Hank Liers, PhD Immune-Assist™ medicinal mushroom extracts

HPDI’s amazing IMMUNE-ASSIST™ mushroom formula is a combination of more than 200 different polysaccharides, derived from the enzymatic breakdown of complex organic plant material from six different species of organically grown medicinal mushrooms. These include Agaricus blazei, Cordyceps hybrid (sinensis and militaris), Lentinula edodes (shiitake)Grifola frondosa (maitake)Ganoderma lucidum (Reishi), and Coriolus versicolor.Immune-Assist™

IMMUNE-ASSIST™ Daily Formula contains simple polysaccharides similar to many other products on the market, but it also contains much more complex polysaccharides like the cross-linked beta mannans and beta-glucans into the same molecule. This is why Immune-Assist™ shows such a greater range of immuno-modulation bioactivity than other bran based supplements. Included among the important substances in Immune-Assist™ are Arabinoxylane, Lentinan, Grifolan (Dr. Nanba’s original Maitake D-Fraction), PSK and PSP, and Active Hemicellulose Correlated Compound (AHCC).

Many mushroom-derived polysaccharides appear to fit the accepted criteria for immunomodulators or biological response modifiers (BRM) compounds. They cause no harm and place no additional stress on the body, they assist the body to adapt to the various environmental and psychological stresses, and they have a non-specific action on the body, supporting all the major systems, including nervous, hormonal, and immune systems, as well as regulatory functions.

MEDICINAL MUSHROOM EXTRACTS: ONE OF THE MOST POWERFUL IMMUNE MODULATORS KNOWN

Recent scientific research has shown that medicinal mushrooms grown on vegetable sources (such as millet, rice bran, buckwheat, milo, etc.) enzymatically activate a process whereby complex cross-linked polysaccharides from the vegetable sources are converted to biologically active immunomodulators. As you will see from the discussion below, the polysaccharides produced by this process are effective and safe immune stimulants.

Medicinal mushroom research has focused on discovering compounds that can modulate positively or negatively the biological response of immune cells. Certain mushroom derived-glucans and polysaccharide-bound proteins have been shown to act as immunomodulators, where these polymers interact with the immune system to upregulate or downregulate specific aspects of the responses of the host and this may result in various therapeutic effects.

Whether certain compounds enhance or suppress immune responses can depend on a number of factors including dosage, route of administration, timing and frequency of administration, mechanism of action or the site of activity.

The most effective polysaccharides isolated from mushrooms (fruit-body, submerged, cultured mycelial biomass or liquid culture broth) are either water-soluble β-D-glucans, β-D-glucans with heterosaccharide chains of xylose, mannose, galactose, or uronic acid or β-D-glucan-protein complexes – proteoglycans.

While the role of medicinal mushrooms in immunomodulation represents the central theme of much of the conducted research, it is pertinent to observe that many of the medicinal mushrooms have been highly valued for other medicinal properties including cholesterols control, blood pressure support, blood sugar support, assistance with viral and bacterial balance, and antioxidant and free radical scavenging.

The safety criteria for mushroom-derived β-glucans have been exhaustively carried out in pre-clinical experiments. Acute, subacute, and chronic toxicity tests have been carried out together with administration during pregnancy and lactation with no adverse effects. There were no anaphylactic reactions and no effects in mutagenicity and haemolysis tests, blood coagulation and a wide range of other regulatory tests. There was no evidence of genotoxicity. Similar results have been obtained with other β-glucans. When applied to humans in Phase 1 clinical tests, the β-glucans demonstrate remarkably few adverse clinical reactions.

In the 2001 report Medicinal Mushrooms: Their Therapeutic Properties and Current Medical Usage, a wide variety of mushroom polysaccharides, including Lentinan (from L. edodes), Schizophyllan (from S. commune), PSK and PSP (from Trametes versicolor), and Grifron-D (from the Maitake mushroom G. frondosa) and others are described, and their properties are shown to satisfy the criteria for biological response modifiers. Many of these mushroom-derived polymers potentiate the host’s innate (non-specific) and acquired (specific) immune responses in a similar manner, where they activate many kinds of immune cells that are vitally important for the maintenance of homeostasis.

Key innate responses that are stimulated by these mushroom derived-β-glucans or polysaccharide-protein complexes include host T-cells (such as cytotoxic macrophages, monocytes, neutrophils, natural killer cells, and dendritic cells) and chemical messengers (cytokines such as interleukins, interferon and colony stimulating factors) that trigger complement and acute phase responses. Moreover, mushroom polysaccharides or polysaccharide-protein complexes are considered as multi-cytokine inducers that are able to induce gene expression of various immunomodulatory cytokines and cytokine receptors.

In addition, acquired responses are also enlisted, where lymphocytes that govern antibody production (B cells) and cell-mediated cytotoxicity (T-cells) are stimulated. While the immune system is shrouded in tremendous complexity, our current understanding shows that it is regulated in an orchestrated dynamic manner.

Mushroom-derived polysaccharides have shown therapeutic activities in both pre-clinical models and in clinical trials. Although the mechanism of their action is still not completely clear, Lentinan, Schizophyllan, PSP, PSK and other mushroom polysaccharides appear to mediate their activity by activation or augmentation of the host’s immune system (via stimulated cytotoxic macrophages, cytotoxic T-cells and antibody-mediated cytoxicity of targeted cells), rather than direct cytotoxicity.

Thus, both cell-mediated immune responses against the target T-cells initiated by macrophage-lymphocyte interactions and cytoxicity induced by antibodies to target T-cells are believed to contribute to the elimination of abnormal cells. Recent evidence suggests that several mushroom polysaccharides may also possess cytotoxic properties. Grifron-D from G. fondosa mushroom was reported to induce apoptosis (programmed cell death) in human prostate cell-lines.

IMMUNE-ASSIST™ DAILY FORMULA INCORPORATES POLYSACCHARIDE EXTRACTS FROM SIX MEDICINAL MUSHROOMS

In China, Japan, Korea, and more recently in the USA, hundreds of mushroom species have been studied during the past 30 years. Extracts from most of the medicinal mushrooms show a common property of enhancing immune function by modulating cell-mediated immunity. Simply put, such mushroom extracts seem to turn on cells in the immune system, which appear to have significant healing properties. In fact, three different drugs extracted from mushrooms have been approved by the Japanese equivalent of FDA (that is, the Japanese Health and Welfare Ministry). These three are lentinan, derived from shiitake; PSK, derived from coriolus versicolor; and schizophyllan, derived from suehirotake.

Based on the latest research a USA-based company (Aloha Medicinals, Inc.) has formulated for Health Products Distributors, Inc. IMMUNE-ASSIST™ Daily Formula. This formula contains more than 200 different polysaccharides, derived from the enzymatic breakdown of complex organic plant material from six different species of medicinal mushrooms. These include Agaricus blazei, Cordyceps hybrid (sinensis and militaris), Lentinula edodes (shiitake)Grifola frondosa (maitake)Ganoderma lucidum (Reishi), and Coriolus versicolor.

Immune-Assist™ Medicinal Mushrooms

RESEARCH RELATED TO MUSHROOMS CONTAINED IN IMMUNE-ASSIST™

Shiitake is now the most popular and most cultivated exotic mushroom in the world. In China, shiitake has a history that dates back to the Ming Dynasty (1368–1644 ACE). The mushroom was used not only as a food but was taken as a remedy for upper respiratory diseases, poor blood circulation, liver trouble, exhaustion and weakness, and to boost chi, or life energy. It was also believed to prevent premature aging.

Coriolus (or Trametes) versicolor is the most thoroughly clinically researched mushroom. An extract of Coriolus versicolor known as PSK is sold in Europe and Japan. It is an immunostimulant; demonstrates anti-viral activity; enhances T-cell proliferation; and has been shown to improve both disease-free and survival rates in patients.

Maitake may be even more potent than any of the other mushrooms previously studied. This legendary giant mushroom has been studied for its anti neoplastic, anti-diabetic, anti-hypertensive, and anti-hyperlipemic effects since the mid-1980s. Its anti-HIV activity in vitro was demonstrated in tests conducted by the Japan Institute of Health and the US National Cancer Institute in early 1992. Among various extracts obtained from the Maitake mushroom, a specific extracted fraction named Maitake D-fraction is the active constituent. This extract contains beta-1, 3-glucans and beta-1, 6-glucans protein-bound polysaccharides. It has demonstrated remarkable cell-protective activity by activating the immune system through oral administration.

The Chinese have long used Cordyceps sinensis and militaris to promote overall good health, and modern research indicates that it does indeed support liver, kidney, heart, and immune system function. Cordyceps has been used to protect the bone marrow and digestive systems of mice from whole body irradiation. One experiment noted that Cordyceps may protect the liver. An experiment with mice indicated the mushroom may have an anti-depressant effect.

Researchers have observed that Cordyceps has a hypoglycemic effect and may be beneficial for people with insulin resistance. Cordyceps mushroom extracts have been shown to stimulate the number of T helper cells, prolong the survival of lymphocytes, enhance TNF-alpha and interleukin 1 production, and increase the activity of natural killer cells. One study indicates that cordyceps can stimulate progesterone production in animal cells.

Reishi possess immunomodulary and immunotherapeutic activities supported by studies on polysaccharides, terpene, and other bioactive compounds isolated from fruiting bodies and mycelia of this fungus. It has also been found to inhibit platelet aggregation, and to lower blood pressure (via inhibition of angiotensin-converting enzyme), cholesterol, and blood sugar.

In an animal model, Reishi has been reported to prevent metastasis, with potency comparable to Lentinan from shiitake mushrooms. The mechanisms by which Reishi may target different stages of abnormal growth development include: 1) inhibition of angiogenesis (formation of new blood vessels created to supply nutrients to the abnormal cell) mediated by cytokines, 2) cytotoxicity, 3) inhibition of migration of the cells and 4) inducing and enhancing apoptosis. Besides effects on mammalian physiology, Reishiis reported to have anti-bacterial and anti-viral activities. Reishi is reported to exhibit direct anti-viral effects with the following viruses: HSV-1, HSV-2, and influenza.

Agaricus blazei is an edible mushroom native to Brazil and cultivated in Japan and the USA for its medicinal uses. It has been used to treat arteriosclerosis, hepatitis, hyperlipidemia, diabetes, dermatitis, and neoplasms. In vitro experiments and studies done in mice have shown that Agaricus has immunomodulatory and antimutagenic properties. The polysaccharides and anti-angiogenic compounds present in Agaricus are thought to be responsible for its therapeutic properties. Such effects are believed to be exerted by immunopotentiation or direct inhibition of angiogenesis.

ACTIVE HEMICELLULOSE CORRELATED COMPOUND (AHCC) AS A COMPONENT OF IMMUNE-ASSIST™ DAILY FORMULA

AHCC is produced by from the enzymatic action of vegetable sources with mycelial extracts from several different mushrooms. There is about four times more AHCC in each dose of Immune-Assist™ than there is in other AHCC products on the market.

AHCC is a food substance that contains a broad range of polysaccharides. It is believed that a special polysaccharide with a molecular weight of about 5,000 and an alpha 1,4 glucan linkage in this mushroom extract is primarily responsible for the powerful immune enhancing effects on natural killer cells. A heavier polysaccharide in the extract appears to have a powerful stimulating effect on macrophages which, in turn, further stimulates the immune system including a number of cytokines (Interleukin-2, Interleukin-12, TNF, and Interferon). Furthermore, some research has indicated that components of AHCC may have direct cytotoxic effects on unhealthy cells.

NATURAL KILLER CELLS

The human immune system is comprised of more than 130 subsets of white blood cells. Natural Killer (NK) cells make up roughly 15% of all human white blood cells. They provide the first line of defense for dealing with any form of invasion to the body. Each NK cell contains several small granules that act as chemical destroyers. Once an NK cell has recognized an unwanted cell, for example, it attaches itself to the cell’s outer membrane and injects these granules directly into the interior of the cell. The granules then destroy the cell within five minutes. The undamaged NK cell then moves on to other cells and repeats the process. When the immune system is particularly strong, active NK cells will often take on more than one cell or other infected cells at the same time.

NK CELL ACTIVITY, NOT NUMBER, DETERMINES THE STRENGTH OF THE IMMUNE SYSTEM

Unlike other white blood cells, inadequate numbers of NK cells are very rarely a problem. Instead, it is the activity of the cells that generally determines whether one is sick or healthy. As long as the NK cells are active, everything remains under control. If NK cells lose their ability to either recognize or destroy the invader, however, the situation can deteriorate rapidly. In many patients with serious health conditions, NK cell activity is probably the primary criteria for estimating the chances of survival. It is commonly accepted that when NK cells cease to function, the end is near.

In addition, research has now confirmed that individuals with low NK cell activity are significantly more susceptible to autoimmune diseases, chronic fatigue syndrome, viral infections and the development of abnormal growths.

Doctors can test NK cell activity with a test called the NK cell function test. Basically, a blood sample is taken from the patient and placed in a vial containing appropriate live cells. After four hours, a count is taken to determine what percentage of the cells have been destroyed by the NK cells. The higher the percentage, the more active the cells. This test is referred to as the four hour Chromium-release assay. Your doctor can order the test from Immune Sciences Lab in Beverly Hills, CA at (310) 657-1077.

HOW IMMUNE-ASSIST™ DAILY FORMULA INCREASES NK CELL ACTIVITY AND IMMUNITY

The capacity of Immune-Assist™ to boost NK activity and overall immunity appears to stem from the following:

1) It increases the number of explosive granules in NK cells. The more granules an NK cell carries, the more unhealthy cells it can destroy.

2) Oral ingestion can increase NK activity as much as 300% (or even higher).

3) It increases interferon (IFN) levels. Interferon is another potent compound produced by the body that both inhibits the replication of viruses and other parasites and increases NK cell activity.

4) It increases the formation of TNFs. TNFs are a group of proteins that help destroy unwanted cells.

5) It increases number and the activity of other lymphocytes, especially T-cells (up to 200%) and macrophages.

6) It stimulates cytokine (IL-2, IL-12, TNF, and IFN) production, which stimulates immune function.

SUPPLEMENT FACTS

COMPOSITION: Two vegetarian capsules provide the following percentage of the Daily Value:

NUTRIENT AMOUNT % Daily Value
Proprietary Beta-Glucan complex plus nucleosides and other bioactive compounds extracted from six well-known, organically grown medicinal mushrooms: Agaricus blazei, Cordyceps sinensis and Cordyceps militaris, Lentinula edodes, Grifola frondosa, Ganoderma lucidum, and Coriolus versicolor. 1,000 mg *

* No established Daily Value

USAGE

DIRECTIONS: As a dietary supplement take two capsules per day in divided doses, or as recommended by a health care professional. In severe conditions, we suggest six (6) capsules per day for two weeks to build up immune activity, then maintaining a dosage of two (2) capsules per day. Alternatively, Immune-Assist™ can be taken at the time of exposure or first signs of illness, in which case we recommend taking two caps three times per day.

INGREDIENTS: IMMUNE-ASSIST™ contains a proprietary organic grown blend grown on organic white milo (growing substrate) and veggie capsule.

IMMUNE-ASSIST™ does not contain: wheat, rye, oats, corn, barley, gluten, soy, egg, dairy, yeast, GMOs, sugar, wax, preservatives, colorings, or artificial flavorings.

REFERENCES

1) Healing Mushrooms by Dr. Georges Halpern, MD, PhD, 2007.

2) Medicinal Mushrooms: Their Therapeutic Properties and Current Medical Usage with Special Emphasis on Cancer Treatments. Smith, Rowan and Sullivan, 2001.

3) Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides (PDF 269 kb). A peer-reviewed article by Dr. Solomon Wasser of University of Haifa, Israel, 2002.

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VITAMIN B12: THE NEGLECTED NUTRIENT

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

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

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

vitamin B12

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

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.

vitamin B12 salmon

Salmon is a good source of Vitamin B12

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

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

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

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

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 – 5 mg methylcobalamin sublingual lozenge

Vitamin B12 – 5 mg Methylcobalamin sublingual lozenge.

VITAMIN B12 DEFICIENCY

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

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

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

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

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.
Metabolic Pathway

 

3. Vitamin B12, bound to protein in food, is released by the activity of hydrochloric acid and gastric protease in the stomach. When synthetic vitamin B12 is added to fortified foods and dietary supplements, it is already in free form and, thus, does not require this separation step. Free vitamin B12 then combines with intrinsic factor, a glycoprotein secreted by the stomach’s parietal cells, and the resulting complex undergoes absorption within the distal ileum by receptor-mediated endocytosis. Approximately 56% of a 1 mcg oral dose of vitamin B12 is absorbed, but absorption decreases drastically when the capacity of intrinsic factor is exceeded (at 1–2 mcg of vitamin B12).

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

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

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

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

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

Groups at Risk of Vitamin B12 Deficiency

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

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

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

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

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

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

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

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

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

Health Risks from Excessive Vitamin B12

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

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

Interactions with Medications

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

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

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

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

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

REFERENCES

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

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

ABSTRACT

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.

 

INTERNET REFERENCES

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IRENA OSSOLA UPDATE – ROLE OF SUPPLEMENTS IN PROFESSIONAL CYCLING

Irena Ossola pro cyclist nutritional supplementsHPDI’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

Irena Ossola

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 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.

Beginning August:

“As I am now at the beginning of my touring/working season, I like to use this time as my sort of “off time” for supplements. Regarding vitamins and other nutritional supplements, 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. Yet, I also know I will feel the difference without a constant flow of vitamins and supplements from Health Products Distributors, Inc.”

Beginning September:

“Now that I am in my moment of break and I’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.”

Beginning October:

“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, Inc. 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, Essential Fats Plus E, 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 (Essential Fats Plus E), and Rejuvenate! high-RNA superfoods (Rejuvenate! Original Greens, 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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What I’d Really Love to Tell You About the Methylation Cycle

Dr. Hank Liers, PhD geneticsI 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.

 

Methylation Cycle

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:

  1. Influences the genetic expression that parents give their children and helps guide the development of the embryo.
  2. Is needed by the nervous system to produce neurotransmitters and maintain the nerves.
  3. Mobilizes fats and cholesterol so they do not accumulate where they are harmful, such as the arteries and liver.
  4. Regulates hormones, including, estrogen, adrenaline, and melatonin.
  5. Detoxifies harmful chemicals and histamine a prime substance involved in inflammation.
  6. Helps repair damaged proteins in the cells so they can function properly.
  7. Protects the DNA in the genome (genetic code) to reduce the chances of mutation.
  8. 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).

GENETICS

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:

  • Alzheimer’s disease
  • Asthma
  • Atherosclerosis
  • Autism
  • Bipolar disorder
  • Bladder issues
  • Blood clots
  • Breast problems
  • Chemical sensitivity
  • Chronic fatigue syndrome
  • Down syndrome
  • Epilepsy
  • Fibromyalgia
  • Gastric problems
  • Glaucoma
  • Heart murmurs
  • High blood pressure
  • Irritable bowel syndrome
  • Leukemia
  • Male infertility
  • Methotrexate toxicity
  • Migraines with aura
  • Multiple sclerosis
  • Myocardial infarction
  • Nitrous oxide toxicity
  • Parkinson’s disease
  • Pulmonary embolisms
  • Schizophrenia
  • Stroke
  • Thyroid issues
  • Unexplained neurologic disease
  • Vascular dementia

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.

MULTIVITAMINS

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.

Hank & Brian's Mighty Multi-Vite multivitamin methylation cycle

Multi Two Caps or Tablets methylation cycle

B COMPLEX

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.

B-Complex-50 full spectrum B vitamins with coenzyme forms methylation cycle

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 methylation cycle

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.

Vitamin B-12 5 mg methylcobalamin sublingual lozenge methylation cycle

Vitamin B-12 – 5 mg Methylcobalamin sublingual lozenge.

MINERALS

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 key B vitamins methylation cycle

MYO-MAG with 100 mg magnesium per serving and key B vitamins.

Health Products Distributors provides 25 mg zinc/serving in its Double Zinc Plus supplement. 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 methylation cycle

Double Zinc Plus supplement with P5P and 25 mg zinc

SUMMARY

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.

RELATED HPDI BLOG ARTICLES

Homocysteine Genetics – Coenzyme B Vitamins

 

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OMEGA-3 ESSENTIAL FATS REMAIN “ESSENTIAL” – A REBUTTAL FROM OMNS

Fred Liers PhD omega-3 essential fats plus e EFA formulaOmega-3 essential fatty acids (EFA) are critically important for health. That is the reason we at HPDI include them in our foundational supplements system in the form of our Essential Fats Plus E formula. Essential Fats Plus E provides a balanced ratio of 4:1 omega-3 EPA to omega-6 GLA fatty acids proven to optimally support health.

As important as Omega-3 fats are in good health, various studies conclude they are of little value. In order to help clarity the fallacies found in such studies, this month we re-print the recent article “Omega 3 Fatty Acids and Cardiovascular Disease” from the Orthomolecular News Service (OMNS).

BACKGROUND

Essential fats including Omega-3 and Omega-6 are so important to health that we consider them as foundational or “core” to basic nutrition as multivitamins, antioxidants/vitamin C formulas, and high-RNA superfoods, like Rejuvenate! Plus.

Many of today’s health problems relate to deficiencies in Omega-3 essential fatty acids rather than overabundance of it. It makes sense for everyone to supplement their diets with at least a minimum amount of essential fats. This is addition to consuming foods high in Omega-3 (and Omega-6) essential fats, including leafy greens, nuts, seeds, and seed oils. Also, small amounts of wild-caught fish from clean waters. Preferably these fish would come from low on the food chain, such as sardines, herring, or young mackerel, for example.

In December 2107, my father Hank Liers, PhD, wrote “The Truth about Essential Fatty Acids.” In his article, he delves into detail about why essential fatty acids are critical for health.

The diagram below from Dr. Hank’s article shows in detail the pathways for the production and use of fatty acids in the body. In the figure the metabolic pathways (running left to right) for four fatty acids types are shown (top – Omega-3, second – Omega-6, third – Omega-9, bottom – Omega-7). Notice that only the omega-3 and omega-6 oils are considered to be essential fatty acids because they cannot be made in the body. This means they must come from food.

omega-3 fats omega-6 fats

Furthermore, an additional diagram from Dr. Hank’s article shown below provides details of the omega-6 and omega-3 pathways. Pathway specifics indicate key eicosanoids (series 1 prostaglandins [anti-inflammatory], series 2 prostaglandins [pro-inflammatory], and series 3 prostaglandins [anti-inflammatory]), oil sources, and important nutrient cofactors that are needed for the reactions to take place.

omega-3 fats omega-6 fats

In particular, Dr. Hank discusses how superior benefits to health result from a balanced 4:1 ratio between Omega-3 eicosapentanoic acid (EPA) fatty acids and Omega-6 gamma linoleic acid (GLA).

Below we list some of the functions and benefits obtained when by diet or supplementation the correct ratios and amounts of essential fatty acids are consumed.

• Regulate steroid production and hormone synthesis
• Regulate pressure in the eyes, joints, and blood vessels
• Regulate response to pain, inflammation, and swelling
• Mediate Immune Response
• Regulate bodily secretions and their viscosity
• Dilate or constrict blood vessels
• Regulate smooth muscle and autonomic reflexes
• Are primary constituents of cellular membranes
• Regulate the rate at which cells divide
• Necessary for the transport of oxygen from the red blood cells to tissues
• Necessary for proper kidney function and fluid balance
• Prevent red blood cells from clumping together
• Regulate nerve transmission

Dr. Hank also discusses the fallacy of thinking that supplemental Omega-3 fats alone are sufficient to produce health. That is, despite the relative lack of Omega-3 essential fats and the prevalence of Omega-6 fats in modern diets, it is nevertheless the forms (EPA and GLA)—and the critical 4:1 ratio between them—that makes the difference in how they act synergistically for health. The result of Hank’s scientific understanding of essential fatty acids has resulted in his formulation of a balanced EFA product, Essential Fats Plus E.

Orthomolecular Medicine News Service Article “Omega 3 Fatty Acids and Cardiovascular Disease”

Regarding the Orthomolecular Medicine News Service article “Omega 3 Fatty Acids and Cardiovascular Disease” (republished below) rebutting the “Cochrane Database of Systematic Reviews” which relies on so-called “Evidence Based Medicine” (EBM) to distort truth on Omega-3 essential fatty acids, the fact that Omega-3 fats are under such false attack represents a huge disservice to the public.

While essential fatty acids may not generate profits for corporations—and in fact may lead to improved health outcomes that threaten the use of chemicals and drugs—essential fats nevertheless remain foundational for health.

Above we have shown the important reasons Omega-3 fats and other essential fatty acids are scientifically termed “essential.” And why people continue taking essential fats, and giving them to their families and children, for supporting health and well-being. Primary among these reasons is that you cannot be healthy without them. Hence, they are essential. Why believe anyone who says otherwise?

The bottom line: Omega-3 essential fatty acids are critical for health. Supplementing the diet with them is a good idea for nearly everyone. This is especially true because typical diets are proven to be most deficient in Omega-3 among essential fats.

Below we re-print in full the recent article “Omega 3 Fatty Acids and Cardiovascular Disease” from the Orthomolecular News Service (OMNS) for the benefit of our HPDI blog readers. ~

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FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, Aug 6, 2018

Omega-3 Fatty Acids and Cardiovascular Disease

Commentary by Damien Downing, MBBS, MSB and Robert G. Smith, PhD

The Cochrane Database of Systematic Reviews has just updated its own review: Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease [1]. Here’s our take on it.

Michael Pollan, the brilliant food writer, reckoned you could sum up what to do about nutrition and diets in 7 words; “Eat food, not too much, mostly plants.” That sums up both what’s best for humans and what’s best for the planet.

We reckon you can sum up what’s wrong with evidence-based medicine (EBM) in 10 words; “Evidence is a waste of data; systematic reviews are palimpsests.” You can use that as a knife to quickly dissect this study.

There are many things wrong with this review. Somebody’s PR department has spun the review’s “no clear evidence of benefit” into “evidence of no benefit” – absence of evidence becoming evidence of absence. And clearly the media were entirely happy to take that one and run with it.

Systematic reviews are palimpsests

What’s a palimpsest? Back when things got written on vellum, an animal skin, not on paper, you didn’t throw it away; you recycled it and wrote over the original. It was called a palimpsest.

A systematic review gives an opportunity to write over the conclusions of a whole list of papers with your new version of the truth. You do that by the way that you select and exclude them.

For instance there was a meta-analysis (that’s a systematic review with more numbers) in 2005 that concluded that vitamin E supplements significantly increased the risk of death [2]. The way they did that was to rule out any study with less than 10 deaths – when fewer deaths was exactly the outcome they were supposed to be looking for.

The reason they gave for doing that was “because we anticipated that many small trials did not collect mortality data.” We’re not buying it; they used it as a trick to enable them to get the negative result they wanted – to over-write the findings of a long list of original studies.

And here we have authors doing the very same thing in this omega-3 study – and upping the ante slightly. Now the threshold is 50 deaths. Fewer than that and your study is ruled out of the final, supposedly least biased, analysis . . on the grounds that it’s more biased.

We don’t know how they could keep a straight face while saying (our interpretation); “The studies with fewer deaths showed more benefit from omega-3s, so we excluded them.” At least that’s what happened back in 2004 when the first version of this came out.[3]

But this is the 8th update (we think) and they no longer bother to tell you about what they included or excluded in detail, so we can only assume that if they had changed that exclusion they would have told us.

The weird thing is that they are allowed to do it. Nutrition researcher Dr. Steve Hickey has shown that in systematic reviews there is generally control for bias in the included studies, but none for bias in the actual review and its authors.[4,5]

They found not one example of adequate blinding among 100 Cochrane reviews (like this one); they could all be palimpsests. Do we know that they are fake? No, but it doesn’t matter: what we do know is that we can’t trust them. Nor can we trust this Cochrane review. Things haven’t changed since 2004.

Evidence is a waste of data

Evidence is what lawyers and courts use to find someone Guilty or Not Guilty, and we all know how that can go wrong. It’s a binary system: you’re either one or the other. But at least if you’re on trial all the evidence should be about you and whether you did the crime.

In EBM the evidence is all about populations, not about individuals. When a doctor tells you “There’s a 1 in 3 chance this treatment will work” he is required to base that on big studies, or even systematic reviews. You don’t, and you can’t, know what that means for you because very likely you don’t fit the population profile.

As Steve Hickey (again) said, the statistical fallacy underlying all this states that you have one testicle and one ovary – because that’s the population average! The authors of this study update started off with about 2100 papers that looked relevant. They then excluded 90 per cent of them for various reasons – some of them good reasons, some not.

A smarter way to work would be to data-mine them and look for useful information about sub-groups and sub-effects in all the papers. Is there a particular reason omega-3s might work for you and not for others? Perhaps you can’t stand fish, or are allergic to them, and so are deficient in omega-3s.

But the review system doesn’t allow it, it insists on overall conclusions (about populations), and that’s a colossal waste of data. It also confounds the overall finding of the review – it biases it in fact.

Here’s an example: while most subgroups that made it to the final analysis showed a small reduction in risk from taking omega-3s in one form or another (pills, food, whatever), those who got it from supplemented foods, which we understand means stuff like margarine with added omega-3, showed a 4.3-fold death risk increase!

The problem here is that the effects of omega-3 fatty acids cannot be studied alone as if they were a drug. What counts are all the other components of the diet that affect a person’s health.

Processed foods and drinks that contain many unhealthy ingredients can’t be made healthy by adding small doses of vitamins, minerals, and omega-3 fatty acids. In fact, many processed foods that contain small doses of vitamins and other essential nutrients are unhealthy because they contain large doses of sugar, salt, and harmful ingredients such as preservatives, dyes, and other non-food items.

Why lipids are so important

Part of the problem is that lipids are truly complicated, and not many people, patients, doctors or even scientists, understand them well. You need a good understanding of lipid metabolism to appreciate the difference in metabolism and impact between alpha-linolenic acid (ALA, in food such as oily fish) and extracted oils such as EPA and DHA that are only found at high levels in omega-3 supplements.

At these levels they are effectively new to nature; nobody, indeed no mammal, was exposed to really high doses of DHA until we invented fish oil supplements [6]. Miss that fact and you miss the difference between having people eat fresh oily fish or just using omega-3 margarine!

We know from a variety of studies that a diet containing generous portions of green leafy and colorful vegetables and fruits, moderate portions of eggs, fish, and meat, and supplements of adequate doses of essential nutrients (vitamins and minerals) is effective at lowering the risk for cardiovascular disease.

Adequate doses of both omega-3 (in flax oil, walnuts, fish) and omega-6 (in seed oils such as canola, soybean, peanut) fatty acids are essential for health. Although essential, omega-6 fatty acids are thought to contribute to inflammation throughout the body whereas omega-3 fatty acids are anti-inflammatory.

Omega-3 fatty acids are essential for most body organs including the brain but are found in lower levels than omega-6 fatty acids in most vegetables. Risk for cardiovascular disease can be lowered by adequate doses of vitamins C (3,000-10,000mg/d), D (2,000-10,000 IU/d), E (400-1,200 IU/d), and magnesium (300-600 mg/d) in addition to an excellent diet that includes an adequate dose of omega-3 fatty acids.[7]

(Dr. Damien Downing is a specialist physician practicing in London, and President of the British Society for Ecological Medicine. Robert G. Smith is a physiologist and Research Associate Professor at the University of Pennsylvania Perelman School Of Medicine.)

 

References:

1. Abdelhamid, A, Brown TJ, Brainard JS, et al., (2018) Omega 3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Syst Rev. 7:CD003177. https://www.ncbi.nlm.nih.gov/pubmed/30019766
http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD003177.pub3/abstract

2. Miller ER, Pastor-Barriuso R, Dalal D, et al., (2005) Review Meta-Analysis?: High-Dosage Vitamin E Supplementation May Increase. Annals of Internal Medicine, 142(1), pp.37-46. Available at: http://annals.org/article.aspx?articleid=718049.

3. Hooper L, Thompson RL, Harrison RA, et al.. (2004) Omega 3 fatty acids for prevention and treatment of cardiovascular disease. Cochrane Database Syst Rev. (4):CD003177. http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD003177.pub2/abstract

4. Hickey S, Noriega LA. Implications and insights for human adaptive mechatronics from developments in algebraic probability theory, IEEE, UK Workshop on Human Adaptive Mechatronics (HAM), Staffs, 15-16 Jan 2009.

5. Hickey S, Hickey A, Noriega LA, (2013) The failure of evidence-based medicine? Eur J Pers Centered Healthcare 1: 69-79. http://ubplj.org/index.php/ejpch/article/view/636

6. Cortie CH, Else, PL, (2012) Dietary docosahexaenoic acid (22:6) incorporates into cardiolipin at the expense of linoleic acid (18:2): Analysis and potential implications. International Journal of Molecular Sciences, 13(11): 15447-15463. http://www.mdpi.com/1422-0067/13/11/15447

7. Case HS (2017) Orthomolecular Nutrition for Everyone. Turner Publication Co., Nashville, TN. ISBN-13: 978-1681626574

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