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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™ 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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REJUVENATE! BERRIES & HERBS – SUPERFOOD FORMULA UPDATED

Dr. Hank Liers, PhD Rejuvenate! Berries & Herbs superfoodToday I talk about my REJUVENATE!™ BERRIES & HERBS high-RNA superfood. I designed it to be a super-delicious, intensely berry flavored superfood with no greens. I put in real organic berries—BLUEBERRY, STRAWBERRY, RASPBERRY, and CRANBERRY—so it bursts with true berry flavors! I recently updated the formula, so it is is more delicious and nutritious than ever.

REJUVENATE! BERRIES & HERBS – A COMPLETE SUPERFOOD

Rejuvenate! Berries & Herbs is a delicious high-RNA (390 mg), high-protein (14.6 g) (organic pea and organic rice), high-antioxidant (ORAC value of 14,000+), high fiber (13 g) superfood with a creamy smoothness and rich berry flavor that tastes beyond great! It also boosts health with a complete multivitamin-multimineral sub-formula and important cell-protective herbs (herbal complex) that includes ginger, dandelion, burdock, turmeric, green tea extract, astragalus, and many other health-building herbs.

How to use Rejuvenate! Berries & Herbs? Just mix in water, juices, nut milks, or smoothies to create a drink with superb health benefits. Or use it creatively in foods, such as nut butters, salads, fruits, sauce/dressings, or desserts. It tastes so good, some people like to eat it by itself—or mixed in a little purified water.

rejuvenate berries herbs

HEALTHY AND HIGH-RNA BY DESIGN

Rejuvenate! Berries & Herbs is among HPDI’s premier high-RNA superfoods. That is, Rejuvenate! Berries & Herbs is one of three Rejuvenate! superfoods, which are the world’s first—and only—dedicated high-RNA superfoods. High-RNA nutrition means high in dietary nucleic acids, which Dr. Benjamin S. Frank considers to be essential nutrients, like vitamins and minerals (Dietary Nucleic Acid Nutrition & Therapy). Dr. Frank’s studies demonstrate many benefits of nucleic acids, including: greater energy, endurance, functional strength, easier breathing (anti-anoxic effect), as well as cardiovascular benefits and cosmetic benefits (smoother skin and a more youthful appearance).

Highlights of Rejuvenate! Berries & Herbs:

• Delicious Berry Flavor Bursts with Real Organic Berries!
• Powerful Organic and Wildcrafted Cell-Protective Herbs
• High ORAC Value (~14,270 units)
• 390 mg Dietary Nucleic Acids (RNA/DNA) from Vegetarian Sources
• Multiple Prebiotics Supporting your Microbiome
• Gluten Free, Vegan/Vegetarian, No Artificial Ingredients
• Mixes Well with other Rejuvenate!™ Superfoods

My updated formula (as of 12/2018) features, per serving:

– 2.6 g more protein (14.6 g total)
– Very little sugar (1.2 g total)
– 7.0 g more fiber (13 g total)
– 100 mg of organic BiAloe® aloe vera gel powder with over 18% acemannan
– 700 mcg of folate as 5-MTHF (natural, coenzyme folate)
– A smooth & delicious taste (even better than before!)

Given all the upgrades I recently made to the formula, I certainly hope you will give it a try. I’m so happy with it, and I use it daily. Berries & Herbs hardly feels (or tastes!) like a nutritional supplement. But believe me, there are few superfoods anywhere that provide as much nutrition—or nutrient density!

HIGHEST QUALITY INGREDIENTS – INCLUDING ORGANIC AND WILDCRAFTED

To give you a better idea of the high-quality ingredients I put into Rejuvenate! Berries & Herbs, check out this complete list of ingredients:

INGREDIENTS: REJUVENATE! BERRIES & HERBS contains: pea protein*, rice protein*, flax seed powder*, rice bran solubles, d-ribose, cranberry powder*, blueberry powder*, raspberry powder*, strawberry powder*, nutritional yeast, sunflower lecithin, inulin (from chicory root), broccoli sprouts powder*, mannitol, xylitol* (from hardwood), magnesium malate, VitaBerry® Plus† (from freeze dried wild blueberry, cranberry, raspberry, strawberry, prune, cherry, wild bilberry, whole grape powders, resveratrol, and quercetin), l-lysine hydrochloride, mixed berry flavoring* (on gum acacia), vanilla flavoring* (on gum acacia), RNA (from yeast), magnesium ascorbate, chlorella growth factor (CGF), burdock root powder*, astragalus powder*, turmeric root powder*, ginger root powder*, digestive multienzyme complex, choline bitartrate, malic acid, dulse*, kelp*, aloe vera* (BiAloe® concentrate), n-acetyl-l-cysteine, rutin, milk thistle extract, green tea extract, licorice root powder*, dandelion root powder*, rhodolia extract, inositol, biotin, stevia leaf extract, alpha lipoic acid, d-alpha tocopheryl succinate, niacinamide (Vit. B3), whole grape extract, high-gamma mixed tocopherols, phylloquinone (Vit. K1), immune assist mushroom extract, pantothenic acid, resveratrol, methylcobalamin (Vit. B12), pyridoxal-5’-phospate (Vit. B6), thiamin diphosphate (Vit. B1), riboflavin-5’-phosphate (Vit. B2), l-selenomethionone, cholecalciferol (Vit. D3), and calcium L-5-methyltetrahydrofolate.

*Organic ingredient
†VitaBerry Plus® is a registered trademark of VDF Futureceuticals, Inc.

Rejuvenate berries and herbs nutrition facts table

Rejuvenate! Berries & Herbs is available from Health Products Distributors, Inc.:

Try Rejuvenate! Berries & Herbs  (organic and wildcrafted berries & herbs)

You may also like: Rejuvenate! PLUS (light, sweet green superfood)

There are three Rejuvenate! superfoods. Which one is best for you? See our Rejuvenate!™ comparison page.

BLOG ARTICLE:

TASTY SMOOTHIE WITH REJUVENATE! BERRIES & HERBS by Fred Liers

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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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EXCITING NEW TERRAFLORA SYNBIOTIC

Terraflora Synbiotic

Dr. Hank Liers, PhD Terraflora synbioticIt has finally arrived — the exciting new Terraflora™ synbiotic. A synbiotic is a combination of probiotics and supporting prebiotics. This advanced soil-based organisms formula fills the need for a superb probiotic/prebiotic in Health Products Distributors’ arsenal of highly effective formulas. Terraflora is extremely supportive of your entire microbiome and gut-based immune system.

 

ADVANCED GUT MICROBIOME SUPPORT

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 various components of our environment. Scientists estimate that 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 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.

The optimal balance of bacteria can be altered in many ways such as broad spectrum antibiotics that kill bacteria in the gut indiscriminately; prescription medications; disease-carrying bacteria, fungi, parasites, and yeasts; stress; lack of sleep; poor diet & lifestyle; geography and travel; and physical disconnection with nature.

Researchers have shown that changes in gut bacteria even affect the brain and personality. For example, germ-free mice have been shown to be dramatically more anxious and hyperactive than their counterparts with a normal microbiome. These changes have also been associated with neurochemical changes in the mouse brain.

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.

Terraflora

FEATURES OF TERRAFLORA

Terraflora is a novel broad spectrum synbiotic formulated with a combination of spore form probiotics, and advanced, food-based, ancient prebiotics designed for robust support of gastrointestinal health.

  • Innovative gut microbiome support
  • Multi-strain, soil-based, beneficial bacteria to support microbial diversity in the GI tract
  • Proprietary blend of ancient, wild-harvested, certified organic prebiotic support
  • Terraflora’s advanced formulation of beneficial strains and ancient prebiotics are designed to support the biodiversity reflected in ancestral diets
  • Shelf stable and requires no refrigeration
  • Highly bioavailable strains are protected by a natural seed-like structure, guarding against environmental factors and stomach acid
  • Strains effectively generate highly bioavailable riboflavin (vitamin B2) and antioxidant carotenoids, right at the sight of absorption
  • Induces anti-inflammatory effects to foster gut homeostasis
  • Supports immune health

TERRAFLORA KEY BENEFITS

VIABILITY – The natural seed-like structure encasing the probiotc bacteria in Terraflora protects them against degradation by stomach acid, so they reach their target destination — the lower GI tract — intact and alive.

ADVANCED PREBIOTIC SUPPORT – Uniquely formulated with organic seaweeds (see reference 2 below), mushroom extracts (see reference 1 below), and humic acid (see reference 3 below). Terraflora’s advanced prebiotic complex contains a diverse spectrum of naturally occurring food-based polyphenols and polysaccharides designed to support healthy intestinal flora

ANTIOXIDANT BENEFITS – Terraflora features Ribospore™ (Bacillus pumilus) and Bacillus megaterium EM144™, two novel probiotic strains shown in studies to produce highly bioavailable, gastric stable antioxidant carotenoids, right at the site of absorption.

CONVENIENT — NO REFRIGERATION REQUIRED! – To ensure potency and viability, most probiotics require refrigeration and have a short shelf life. The inherently resilient bacteria in Terraflora are heat-stable, and require no refrigeration, uniting convenience and efficacy.

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.

Why are soil-based probiotics so popular among clinicians, and what makes them so important?  The answer to this question lies in an understanding of the human gut microbiome.

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 arguably 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.

Terraflora bridges the lost connection to our natural environment, with a sophisticated probiotic bio-complex of specific, commensal Bacillus strains. Selected for their unique characteristics, Bacillus are gram-positive bacteria that can exist in two forms. Under favorable conditions the bacteria grow in a vegetative form, but when starved of nutrients they differentiate into a dormant life form known as an “endospore” or simply a “spore”. These spores come alive when introduced to an ideal environment, like the human gut.

Terraflora’s innovative DNA verified strain combination introduces Ribospore™ (Bacillus pumilus) and Bacillus megaterium EM144™, microorganisms scientifically proven to effectively produce highly bioavailable antioxidants and riboflavin, right at the site of absorption. Riboflavin is an essential nutrient for maintaining a healthy digestive tract.

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 PINNATIFIDA (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 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.

TERRAFLORA INGREDIENTS

Probiotic Bio-Complex: 1 Billion Viable Cells per serving
Ribosporea  (Bacillus pumilus)
Bacillus megaterium EM144a
Bacillus subtilis
Bacillus clausii
Bacillus coagulans


Prebiotic Bio-Complex: 850 mg per serving
Larch Arabinogalactan (Larix spp.), Reishi (Ganoderma lucidum) Extract (fruiting body), Wild-Harvested Chaga (Inonotus obliquus) Extract (fruiting body), Wild-Harvested Nova Scotian Bladderwrack (Fucus vesiculosus) Extract (thallus), Wild-Harvested Patagonian Wakame (Undaria pinnatifida) Extract (sporophyll), and Humic Acids.

Other Ingredients: Plant cellulose (veggie capsule)

Contains No: dairy, wheat, yeast, gluten, corn, sugar, soy, shellfish, tree nuts, or GMOs. Made without stearates, fillers, binders, flow agents, or additives of any kind.

DIRECTIONS

Serving Size: Two Veggie Capsules            Servings Per Container: 30

Suggested Use: Take 1–2 capsules per day with or without food, or as recommended by your health care professional.

If you are pregnant, nursing, or have a medical condition, consult your healthcare practitioner before use.

REFERENCES

  1. Paper regarding the use of mushroom extracts as prebiotics:

    A Critical Review on Health Promoting Benefits of Edible Mushrooms through Gut Microbiota
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618583/

    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.

    2. Paper regarding the use of Seaweeds as prebiotics:
    Prebiotics from Marine Macroalgae [seaweeds] for Human and Animal Health Applications
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920542/

    Abstract
    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.

    3. Paper regarding the use of Humic Acids as prebiotics:
    Impact of humic acids on the colonic microbiome in healthy volunteers
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920542/

    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.

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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.

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