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THE AMAZING HEALING POTENTIAL OF NATURAL NRF2 ACTIVATORS

Dr. Hank Liers, PhD natural nrf2 activators healing potential

When I first learned about Nrf2 activators in early 2012, I became quite enthusiastic about new knowledge that natural substances called polyphenolic compounds had the ability to activate this transcription factor. Once released in the cell Nrf2 can migrate to the nucleus and cause the body to endogenously produce high levels of key protective/antioxidant enzymes.

Also, I actively began the development of a product called Ultimate Protector that contains many concentrates and extracts from fruits, vegetables, and herbs. This product functions as 1) an excellent source of many Nrf2 activators, 2) a source of powerful antioxidants exhibiting an extremely high ORAC5.0 value per serving, and 3) a source of non-GMO Vitamin C.

More recently (July 2019) I have updated the product to Ultimate Protector+ that contains some exciting new ingredients that are now available on the market including SFB® (Standardized Fruit Blend) that contains among others mangosteen, goji berry, pomegranate, and apple extracts (click on the ingredient name to see detailed blog articles concerning these). In addition, I have added significant amounts of ingredients that are well known as potent Nrf2 activators and antioxidants including Green Tea extract and VinCare® whole grape extract.

 

Ultimate Protector+

New Ultimate Protector+

 

It is interesting to note that over 16 years ago I formulated a wonderful antioxidant formula called PRO-C™. PRO-C™ contains Buffered Vitamin C (in the form of powdered calcium, magnesium, and zinc ascorbates), high-potency Grape Extract (from grape pulp, skins, and seeds), Green Tea Extract, reduced Glutathione, N-Acetyl-L-Cysteine (NAC), R-Lipoic Acid, coenzyme forms of Vitamin B2 and Vitamin B6, and Selenium.

PRO-C™ has been one of the most effective products at supporting health I have ever formulated. Our current knowledge shows that PRO-C™ contains four effective Nrf2 activators, selenium needed for glutathione peroxidase functioning, Vitamin B2 and Vitamin B6 that support the effectiveness of glutathione, and antioxidants including Vitamin C and glutathione. I recently wrote a blog article titled PRO-C™ SUPER ANTIOXIDANT FORMULA that provides details concerning this formula.

My current personal list of supplements that I (and my wife) take every day includes both Ultimate Protector™ and PRO-C™. We feel gifted to have these products available to us!!

In this article, I will provide greater insight into the natural sources of Nrf2 activators and how they perform in the body.

SOME KEY ENZYMES MODULATED BY Nrf2 ACTIVATORS

Activation of Nrf2 results in the induction of many cytoprotective proteins. We have seen articles that claim over 200 different enzymes can be produced in the body by Nrf2 activators, but have also seen reference that over 4,000 enzymes may be produced!  Examples of some of the key enzymes are shown below:

  • NAD(P)H quinone oxidoreductase 1 – a prototypical Nrf2 target gene that catalyzes the reduction and detoxification of highly reactive quinones that can cause redox cycling and oxidative stress.
  • Superoxide dismutases (SOD) – enzymes that catalyze the dismutation of superoxide (O2) into oxygen and hydrogen peroxide. Thus, they are an important antioxidant defense in nearly all cells exposed to oxygen where superoxide is one of the main reactive oxygen species. SOD is known to provide powerful antinflammatory activity.
  • Glutamate-cysteine ligase which is the rate-limiting step in the synthesis of glutathione (GSH), a very powerful endogenous antioxidant. Glutamate-cysteine ligaseis a characteristic Nrf2 target gene, which establish Nrf2 as a regulator of glutathione, one of the most important antioxidants in the body.
  • Heme oxygenase-1 (HO-1) is an enzyme that catalyzes the breakdown of heme into the antioxidant biliverdin, the anti-inflammatory agent carbon monoxide, and iron. HO-1 is a Nrf2 target gene that has been shown to protect from a variety of pathologies, including sepsis, hypertension, atherosclerosis, acute lung injury, kidney injury, and pain.
  • The glutathione S-transferase (GST) family includes cytosolic, mitochondrial, and microsomal enzymes that catalyze the conjugation of GSH with endogenous and xenobiotic electrophiles. After detoxification by GSH conjugation catalyzed by GSTs, the body can eliminate potentially harmful and toxic compounds. GSTs are induced by Nrf2 activation and represent an important route of detoxification.
  • The UDP-glucuronosyltransferas (UGT) family catalyze the conjugation of a glucuronic acid moiety to a variety of endogenous and exogenous substances, making them more water soluble and readily excreted. Important substrates for glucuronidation include bilirubin, and acetaminophen. Nrf2 has been shown to induce UGT1A1 and UGT1A6.
  • Multidrug resistance-associated proteins  (Mrps) are important membrane transporters that efflux various compounds from various organs and into bile or plasma, with subsequent excretion in the feces or urine, respectively. Mrps have been shown to be upregulated by Nrf2 and alteration in their expression can dramatically alter the pharmacokinetics and toxicity of compounds.

NATURAL FOODS AND FOOD EXTRACTS PROMOTE THE EXPRESSION OF Nrf2

The March 2011 Epub Biochemical Basis for Functional Ingredient Design from Fruits reports: “Functional food ingredients (nutraceuticals) in fruits range from small molecular components, such as the secondary plant products, to macromolecular entities, e.g., pectin and cellulose, that provide several health benefits.  In fruits, the most visible functional ingredients are the color components anthocyanins and carotenoids.

“In addition, several other secondary plant products, including terpenes, show health beneficial activities.  A common feature of several functional ingredients is their antioxidant function. For example, reactive oxygen species (ROS) can be oxidized and stabilized by flavonoid components, and the flavonoid radical can undergo electron rearrangement stabilizing the flavonoid radical.  Compounds that possess an orthodihydroxy or quinone structure can interact with cellular proteins in the Keap1/Nrf2/ARE pathway to activate the transcription of antioxidant enzymes.

“Carotenoids and flavonoids can also exert their action by modulating the signal transduction and gene expression within the cell. Recent results suggest that these activities are primarily responsible for the health benefits associated with the consumption of fruits and vegetables.”

One of the interesting aspects of the extensive research that has been conducted is the fact that many of the polyphenols that have been shown to activate Nrf2 have been used in natural healing formulas for many years. For example, an article in a November 2010 production titled Nutraceutical antioxidants as novel neuroprotective agent expands on the classes of “antioxidant” compounds that are neuroprotective and operate either via direct antioxidant action or via the keap1-Nrf2 pathway:

“A variety of antioxidant compounds derived from natural products (nutraceuticals) have demonstrated neuroprotective activity in either in vitro or in vivo models of neuronal cell death or neurodegeneration, respectively. These natural antioxidants fall into several distinct groups based on their chemical structures: (1) flavonoid polyphenols like epigallocatechin 3-gallate (EGCG) from green tea and quercetin from apples; (2) non-flavonoid polyphenols such as curcumin from tumeric and resveratrol from grapes; (3) phenolic acids or phenolic diterpenes such as rosmarinic acid or carnosic acid, respectively, both from rosemary; and (4) organosulfur compounds including the isothiocyanate, L-sulforaphane, from broccoli and the thiosulfonate allicin, from garlic.

“All of these compounds are generally considered to be antioxidants.  They may be classified this way either because they directly scavenge free radicals or they indirectly increase endogenous cellular antioxidant defenses, for example, via activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2) transcription factor pathway. Alternative mechanisms of action have also been suggested for the neuroprotective effects of these compounds such as modulation of signal transduction cascades or effects on gene expression. Here, we review the literature pertaining to these various classes of nutraceutical antioxidants and discuss their potential therapeutic value in neurodegenerative diseases.”

DIETARY FLAVONOIDS AS NRF2 ACTIVATORS

One of the ways dietary flavonoids work to confer their multiple health effects is via the keap1-Nrf2 pathway.  That is substances which are both themselves antioxidants and activators of the keap1-Nrf2 pathway produce significant results through keap1-Nrf2 and activating the body’s own antioxidant and defensive systems.

Flavonoids are a large family of polyphenolic compounds synthesized by plants. Many of the common dietary flavonoids are shown in Table 1 below along with their common food sources.

Table 1: Common Dietary Flavonoids

Flavonoid Subclass Dietary Flavonoids Some Common Food Sources
Anthocyanidins  Cyanidin, Delphinidin, Malvidin, Pelargonidin, Peonidin, Petunidin Red, blue, and purple berries; red and purple grapes; red wine
Flavonols  Monomers (Catechins) Catechin, Epicatechin, Epigallocatechin, Epicatechin gallate, Epigallocatecin gallate Dimers and Polymers: Theaflavins, Thearubigins, Proanthocyanidins Catechins: Teas (particularly green and white), chocolate, grapes, berries, apples Theaflavins, Thearubigins: Teas (particularly black and oolong) Proanthocyanidins: Chocolate, apples, berries, red grapes, red wine.
Flavanones Hesperetin, Naringenin, Eriodictyol Citrus fruits and juices, e.g., oranges, grapefruits, lemons.
Flavonols Quercetin, Kaempferol, Myricetin, Isorhamnetin Widely distributed: yellow onions, scallions, kale, broccoli, apples, berries, teas.
Flavones Apigenin, Luteolin Parsley, thyme, celery, hot peppers.
Isoflavones Daidzein, Genistein, Glycitein Soybeans, soy foods, legumes.

In addition to flavonoids many other plant based substances appear to produce health benefits through hormetic effects mediated by Nrf2.  The December 2011 publication Nutritional antioxidants and adaptive cell responses: an update reports: “Many plant antioxidants, intaken through the daily diet or plant-derived dietary supplements, have been shown able to prevent free radical-related diseases by counteracting cell oxidative stress. However, it is now considered that the in vivo beneficial effects of these phytochemicals are unlikely to be explained just by their antioxidant capability.

“Several plant antioxidants exhibit hormetic properties, by acting as ‘low-dose stressors’ that may prepare cells to resist more severe stress. In fact, low doses of these phytochemicals activate cell signaling pathways (being the most prominent examples the modulation of the Nrf2/Keap1 pathway, the NF-κB pathway and the Sirtuin-FOXO pathway) but high doses are cytotoxic.

“Herein we review the adaptive responses induced by the most known plant hormetic antioxidants, which are sulforaphane, resveratrol, curcumin, flavonoids, green tea catechins and diallylsulphides [in garlic], as well as the molecular mechanisms involved in such responses. Furthermore, this review outlines that the hormetic properties of these bioactive plant antioxidants might be successfully employed for realizing health-promoting dietary interventions especially in the field of neurodegenerative diseases and cancer.”

 

Ultimate Protector+

INTERESTING FACTS REGARDING NRF2 ACTIVATORS

1) An interesting fact is that Nrf2 is ubiquitously expressed with the highest concentrations (in descending order) in the kidney, muscle, lung, heart, liver, and brain. 

2) Another important fact is that the well-known nutrition supplement lipoic acid is a potent activator of Nrf2 and thus increases Gluthatione levels, which may explain its protective effect against diabetic co-morbidities. Additionally, the nutritional supplements tocotrienols (active forms of Vitamin E) and N-Acetyl-L-Cysteine (NAC) are also effective Nrf2 activators!

3) We have observed that the natural plant substances with the highest ORAC5.0 values appear to be among the most effective Nrf2 activators. For example, see the table below. In particular, note that Curcumin (98%), Grape Seed Extract, Green Tea Extract, and Reservatrol which are commonly used for their excellent Nrf2 activator effects are the most powerful in-vitro antioxidants . Please note that Ultimate Protector is over 50% more powerful as an antioxidant than the best single plant ingredient.

TABLE 2: ORAC5.0™ COMPARATIVE RESULTS

Ingredient Peroxyl Radical Hydroxyl Radical Peroxy-nitrite Radical Super-
oxide Radical
Singlet O2 Radical Total ORAC5.0
Curcumin 98% 5,750 8,920 906 597 66,290 82,500
Bilberry 25% 7,000 25,000 1,000 16,000 5,000 54,000
Cocoa 10,000 28,000 1,000 11,000 2,000 52,000
Grape Seed Extract 17,000 47,000 1,000 25,000 4,000 94,000
Green Tea Extract 11,000 41,000 2,000 56,000 3,000 113,000
Coffee Berry Extract 5,000 29,000 1,000 1,000 2,000 38,000
Mangosteen 4,000 8,000 1,000 18,000 4,000 35,000
Pine Bark 7,000 23,000 1,000 17,000 2,000 50,000
Resveratrol 12,000 50,000 1,000 8,000 22,000 93,000
ULTIMATE PROTECTOR+ TBD TBD TBD TBD TBD TBD
Results are expressed in micro mole TE/g
4) Here is a list of the ingredients in ULTIMATE PROTECTOR+: USP-grade non-GMO Vitamin C, SFB® standardized fruit blend (~50% polyphenols, high-ORAC powder: 9,000 µmole TE/g) from Grape, Cranberry, Pomegranate, Blueberry, Apple, Mangosteen, Bilberry, Chokeberry, and Goji Berry), Curcumin (standardized extract with 95% curcuminoids), Trans-Resveratrol (98% from Giant Knotweed), Green Tea Extract (93% polyphenols, 50% EGCG), VinCare® Whole Grape Extract (>80% polyphenols, ORAC>19,000 µmole TE/g), Calcium Malate, Magnesium Malate, and Bioperine® (a patented black pepper extract that enhances absorption of all ingredients and is a known Nrf2 activator).

NEUROPROTECTION BY POLYPHENOL STIMULATION OF THE NRF2 / ARE PATHWAY 

Below are two abstracts that discuss how modulation of the Nrf2/ARE pathway by food polyphenols can provide neuroprotection through the activation of the heme-oxygenase enzyme.

Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders. (Oct. 2011)

ABSTRACT

In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general xenobiotic response in the target cells, activating multiple defense genes.

Data from our and other laboratories have previously demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity in different brain cells via the activation of heterodimers of NF-E2-related factors 2 (Nrf2)/antioxidant responsive element (ARE) pathway. Many studies clearly demonstrate that activation of Nrf2 target genes, and particularly HO-1, in astrocytes and neurons is strongly protective against inflammation, oxidative damage, and cell death. In the central nervous system, the HO system has been reported to be very active, and its modulation seems to play a crucial role in the pathogenesis of neurodegenerative disorders.

Recent and unpublished data from our group revealed that low concentrations of epigallocatechin-3-gallate, the major green tea catechin, induces HO-1 by ARE/Nrf2 pathway in hippocampal neurons, and by this induction, it is able to protect neurons against different models of oxidative damages. Furthermore, we have demonstrated that other phenolics, such as caffeic acid phenethyl ester and ethyl ferulate, are also able to protect neurons via HO-1 induction. These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against cognitive decline.

The major green tea polyphenol, (-)-epigallocatechin-3-gallate, induces heme oxygenase in rat neurons and acts as an effective neuroprotective agent against oxidative stress. (Aug. 2009)

ABSTRACT

Oxidative stress induced by hyperglycemia is a key factor in the pathogenesis of diabetic complications, such as neuropathy. Recently, green tea catechins have received much attention, as they can facilitate a number of antioxidative mechanisms and improve glycemic control. The aim of this study was to investigate the cytoprotective effects of (-)-epigallocatechin-3-gallate (EGCG) against oxidative stress damage in a cell line of rat neurons. The role of heme oxygenase 1 (HO-1) induction by EGCG and the transcriptional mechanisms involved were also evaluated.

Immortalized rat neurons (H 19-7) were exposed to various concentrations of EGCG (10-200 microM). After treatments (6 or 24 hours), cells were harvested for the determination of heme oxygenase activity, mRNA levels, and protein expression. Nuclear levels of Nrf2, a transcriptional factor involved in HO-1 activation, were also measured. Neurons were pretreated for 12 hours with EGCG 50 microM or EGCG 50 microM + zinc protoporphyrin IX 10 microM and then exposed for 2 hours to 50 mmicro/mL glucose-oxidase before cell viability was determined.

In cultured neurons, elevated expression of HO-1 mRNA and protein were detected after 6 hours of incubation with 25-100 microM EGCG, and its induction relates with the activation of Nrf2. Interestingly, pre-incubation (12 hours) with EGCG 50 microM resulted in an enhanced cellular resistance to glucose oxidase-mediated oxidative damage; this cytoprotective effect was considerably attenuated by zinc protoporphyrin IX, an inhibitor of heme oxygenase activity.

In this study, we demonstrated that EGCG, the major green tea catechin, induced HO-1 expression in cultured neurons, possibly by activation of the transcription factor Nrf2, and by this mechanism was able to protect against oxidative stress-induced cell death.

 

The following review article abstract shows how natural products containing Nrf2 activator/antioxidant ingredients might be used to support health and anti-aging.

Nrf2/ARE Signaling Pathway: Key Mediator in Oxidative Stress and Potential Therapeutic Target in ALS (July 2012)

REVIEW ARTICLE

Abstract: Nrf2 (nuclear erythroid 2-related factor 2) is a basic region leucine-zipper transcription factor which binds to the antioxidant response element (ARE) and thereby regulates the expression of a large battery of genes involved in the cellular antioxidant and anti-inflammatory defence as well as mitochondrial protection. As oxidative stress, inflammation and mitochondrial dysfunctions have been identified as important pathomechanisms in amyotrophic lateral sclerosis (ALS), this signaling cascade has gained interest both with respect to ALS pathogenesis and therapy. Nrf2 and Keap1 expressions are reduced in motor neurons in postmortem ALS tissue.

Nrf2-activating compounds have shown therapeutic efficacy in the ALS mouse model and other neurodegenerative disease models. Alterations in Nrf2 and Keap1 expression and dysregulation of the Nrf2/ARE signalling program could contribute to the chronic motor neuron degeneration in ALS and other neurodegenerative diseases. Therefore, Nrf2 emerges as a key neuroprotective molecule in neurodegenerative diseases.

Our recent studies strongly support that the Nrf2/ARE signalling pathway is an important mediator of neuroprotection and therefore represents a promising target for development of novel therapies against ALS, Parkinson’s disease (PD), Huntington’s disease (HD), and Alzheimer’s disease (AD). Simultaneous blockage of disease-specific broad toxic signaling cascades in motor neurons and glia may ultimately lead to more efficient neuroprotection in ALS. Stimulation of defense mechanisms that modulate neuroprotective genes which affect both neuronal and glial functions is a novel therapeutic approach and holds great promise. A key molecule to affect a variety of defense mechanisms is the transcription factor Nrf2 which activates the Nrf2/ARE signaling program. Nrf2 acts as master regulator of the cellular antioxidant response by stimulation of over 250 phase II genes that should be referred to as “prolife genes” since they save cells from death.

Nrf2 activation can at once regulate the expression of multiple cytoprotective enzymes that are capable of simultaneous inhibition of major pathogenic pathways described in ALS such as oxidative stress, neuroinflammation, and mitochondrial dysfunction. Decreased Nrf2 expression was found in motor neurons in ALS postmortem brain and spinal cord. We have established the proof-of-concept that the Nrf2/ARE program is a viable target with excellent therapeutic potential for ALS. While there are still multiple gaps of knowledge on the path from Nrf2 dissociation to nuclear localization and its action as transcription factor, activation of the Nrf2 signaling cascade represents a novel and unique attempt to find a cure for ALS and other neurodegenerative diseases by fortifying the intrinsic defense mechanisms of neurons.

CONCLUSION

In this article I have shown how foods such as fruits, vegetables, herbs, and their extracts can stimulate extremely powerful protective enzymes in the body that work to keep us healthy. I strongly suggest that our readers eat an organic diet that emphasizes these foods and highly recommend the use of nutritional supplements such as Ultimate Protector+ and PRO-C™ that can further support the activation of the Nrf2 pathways in the body!

SOURCES

BLOG ARTICLES

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PREVENTING FREE RADICAL DAMAGE WITH ULTIMATE PROTECTOR+

Back in 2012, I learned about Nrf2 activators and was excited about pursuing the development of a supplement that would incorporate the new knowledge we were learning into a effective product for preventing free radical damage. At that time, I published two articles: New Directions for Preventing Free Fadical Damage and Natural Phytochemical Nrf2 Activators for Chemoprevention. I started working on a new Nrf2-activator formula I called Ultimate Protector that incorporated many of the ideas contained in these articles. The product was introduced November 2012.

More recently, in early 2019, I decided to upgrade the product using new information and ingredients. The upgraded product is called Ultimate Protector+. In this article, I provide new details of our design logic and product ingredients. I expect the new formula to be released in July 2019.

Ultimate Protector+

Ultimate Protector+ is new and improved!

PREVENTING FREE RADICAL DAMAGE WITH ULTIMATE PROTECTOR+

Ultimate Protector+™ is a unique cell protection formula that simultaneously meets the needs for high levels of non-GMO Vitamin C, full spectrum antioxidants (high ORAC values), and protective enzyme activators (Nrf2 activators) in a single product. This potent combination of characteristics distinguishes the formula because no other single product available today offers such complete protection. This is the single best formula for preventing free radical damage that is available.

Ultimate Protector+™ provides extremely high levels of natural antioxidants, including high levels of ingredients such as polyphenols, flavonoids, anthocyanidins, oligomeric proanthocyanidins, catechins, curcuminoids, pterostilbene, resveratrol, chlorogenic acid, punicalagins, zeaxanthin and other carotenoids that act powerfully as antioxidants. These antioxidants come from more than 12 plant-based ingredients with demonstrated free-radical quenching capacity. These “exogenous” food-based antioxidants (supplied from outside the body) provide you with immense oxidative defenses that can be used to defend against free-radical assault.

Ultimate Protector+™ contains USP-grade non-GMO Vitamin C , SFB® standardized fruit blend (~50% polyphenols, high-ORAC powder: 9,000 µmole TE/g) from Grape, Cranberry, Pomegranate, Blueberry, Apple, Mangosteen, Bilberry, Chokeberry, and Goji Berry), Curcumin (standardized extract with 95% curcuminoids), Trans-Resveratrol (98% from Giant Knotweed), Green Tea Extract (90% polyphenols, 50% EGCG), VinCare® Whole Grape Extract (>80% polyphenols, ORAC>19,000 µmole TE/g), Calcium Malate, Magnesium Malate, and Bioperine® (a patented black pepper extract that enhances absorption of all ingredients and is a known Nrf2 activator).

Ultimate Protector+™ is contained in a capsule suitable for vegetarians (i.e., a veggie cap) and contains no magnesium stearate.

NUTRITIONAL CONSIDERATIONS AND APPLICATIONS

Ultimate Protector+™ satisfies three distinct needs:

1) The need for a non-GMO Vitamin C product. That is, a Vitamin C formula that avoids protein from genetically modified sources such as corn, potatoes, or beets.

2) The need for a single, powerful antioxidant formula for preventing free radical damage. That is, a single, easy-to-take antioxidant formula offering a broad range of extremely high-ORAC plant source antioxidants. These antioxidants should protect against the full range of free radicals found in the human body including: superoxide anion (O2·-), peroxyl radicals (ROO·), hydroxyl radicals (HO·), singlet oxygen (1O2), and peroxynitrite (ONOO-).

3) The need for a supplement providing a full spectrum of Nrf2 activators. That is, a supplement providing a wide range of natural Nrf2 transcription factor activators that allow the body to make its own antioxidant enzymes (e.g., superoxide dismutase (SOD), catalase, hemeoxygenase, and glutathione peroxidase). Scientific research has shown that these are found naturally in many fruits, vegetable, and herbs. These ingredients provide a wide range of Nrf2 activators that result in significantly high levels of the endogenously produced antioxidant enzymes.

The ways Ultimate Protector+™ satisfies these three needs are discussed below:

1) NON-GMO VITAMIN C / ASCORBIC ACID

High-quality, USP grade Vitamin C has been obtained historically from corn, potatoes, and/or beets. Unfortunately, many of these sources have to a large extent gone to genetically modified (GMO) variants. However, with highly refined production methods and the use of PCR testing, we have been able to obtain final products that are free from GMOs.

In nature, Vitamin C is found generally in plant sources containing polyphenols. Vitamin C and polyphenols work together to provide a high level of antioxidant protection and they support the function of each other in the process. For example, Vitamin C is needed by the body to produce collagen and certain polyphenols (especially oligomeric proanthocyanidins) (OPCs) crosslink the collagen and make it stronger.

2) EXTREMELY HIGH ORAC SOURCES

Free radicals are reactive species that can have adverse effects on normal physiological functions. Studies associate the five major types of free radicals (i.e., hydroxyl, peroxyl, peroxynitrite, singlet oxygen, and superoxide anion) with health conditions such as cardiovascular disease, hypertension, breakdown of vital proteins, chronic inflammation, Alzheimer’s disease, and certain cancers. Avoiding free radical damage is the goal.

Antioxidants function as a vital line of defense against free radicals by blocking their attack on DNA, vital proteins, lipids, and amino acids. Until now, efforts to identify the effect of antioxidants on all five types of free radicals were constrained by limited testing procedures. However, new technological developments have resulted in a comprehensive testing method called the Total ORAC5.0™ assay. Because of the development of the Total ORAC5.0™ test, it is now possible to target and measure the effects of antioxidants on the five major types of free radicals found in the body.

We are currently in the process of testing Ultimate Protector+™ using this new ORAC5.0™ assay. We are confident that our formula offers protection against these five major types of free-radicals because we combine a wide range of extremely high-ORAC fruit, vegetable, and herbal blends. As soon as the results are available (in July 2019), we will update this article with the findings.

3) NRF2 TRANSCRIPTION FACTOR ACTIVATORS

In order to survive under a variety of environmental or intracellular stresses, our cells have developed highly efficient protective mechanisms to protect themselves from oxidative or electrophilic challenges. Proteins that comprise phase II detoxification and antioxidant enzymes provide an enzymatic line of defense against reactive oxygen species (ROS). These enzymes include superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione S-transferase (GST), and glutamate cysteine ligase.

Induction of phase II and antioxidant enzymes are regulated at the DNA/gene level by an antioxidant responsive element (ARE). ARE-mediated gene expression plays a central role in the cellular defense against cellular oxidative damage. Experimental evidence supports the view that induction of ARE-mediated cytoprotective enzymes is a critical and sufficient mechanism to enable protection against disease provoked by environmental and endogenous insults.

One of the key ARE-binding transcription factors is Nrf2. Induction of cytoprotective enzymes in response to ROS, electrophiles, and phytochemicals is a cellular event that is highly dependent on Nrf2 protein. By activating Nrf2 signaling, phytochemicals can increase cellular detoxification and antioxidant enzymes, thereby enhancing removal of ROS and toxic chemicals and preventing disease. Numerous research studies carried out over the last 15 years have demonstrated the effectiveness of a very wide range of Nrf2 activators extracted from fruits, vegetables, and herbs.

For example, a study with sulforaphane (an isothiocyanate present abundantly in cruciferous vegetables) shows that oral administration of this phytochemical can effectively block benzo[a]pyrene-induced forestomach tumors in mice. This protective effect was abrogated in mice that could not produce Nrf2. This supports the critical role of phase II detoxification and antioxidant enzymes in the prevention of carcinogenesis by chemopreventive agents.

Nrf2 is normally bound in the cytoplasm of cells to a protein called KEAP1. However, when an appropriate phytochemical agent attaches to a kinase receptor on the cell wall a phosphate group is released that causes the Nrf2 to be released. Also, there are other mechanisms that allow Nrf2 to be released from KEAP1. The released Nrf2 then migrates into the cell nucleus and causes an antioxidant enzyme (e.g., superoxide dismutase (SOD)) to be fabricated and released. This endogenously produced enzyme then can protect against ROS, electrophiles, and other toxic agents.

In practical experience, it has been found that a combination of multiple polyphenols works significantly better than single ingredients. In fact, in one experiment it was found that a combination of five ingredients all known to be Nrf2 activators was 18 times more effective than any single ingredient. Furthermore, it was found that this combination of five ingredients was able to increase levels of SOD by 30% and catalase by 56% after 120 days of taking the combination.

In view of the considerations above, we include a wide range of Nrf2 activators in Ultimate Protector+™. These include a large variety of freeze-dried and concentrated fruits, vegetables, and herbs. These include Grape, Cranberry, Pomegranate, Blueberry, Apple, Mangosteen, Bilberry, Chokeberry, Goji Berry), Curcumin (standardized extract with 95% curcuminoids), Trans-Resveratrol (98% from Giant Knotweed), Green Tea Extract (93% polyphenols, 50% EGCG), VinCare® Whole Grape Extract (>80% polyphenols, ORAC>19,000 µmole TE/g)

Ultimate Protector+™ includes the following phytonutrients in its array of freeze-dried and concentrated fruits, vegetables, and herbs: polyphenols, flavonoids, anthocyanins, catechins, proanthocyanins, ellagic acid, xanthines, chlorogenic acid, pterostilbenes, resveratrol, phloridzin, quercetin, zeaxanthin, carotinoids, polysaccharides, quinic acid, and more.

The phytochemical ingredients in Ultimate Protector+™ are discussed below:

1. SFB® – (Standardized Fruit Blend)

SFB® is a nutritious, non-GMO blend that provides a broad spectrum of polyphenols, anthocyanins, and other antioxidants derived from water and/or ethanol extracts of grape (Vitis vinifera), cranberry (Vaccinium macrocarpon), pomegranate (Punica granatum) with >75% polyphenols, blueberry (Vaccinium uliginosum), apple (Malus pumilla Mill), mangosteen (Garcinia mangostana), bilberry (Vaccinium myrtillis), chokeberry (Aronia arbutifolia), and goji berry (Lycium barbarum). This powder has an ORAC value in excess of 9,000 µmole TE/g and contains 50% polyphenols.

Polyphenols and anthocyanins are not all created equal. Every fruit, vegetable and herb provides its own set of unique polyphenols and anthocyanins that reside in the body for different lengths of time and in different locations, providing a range of benefits. SFB® has been designed to provide a wide range of plant polyphenols, flavonoids, anthocyanins, catechins, OPCs, zeaxanthin and other carotinoids, etc. Published research associates these plant ingredients with healthy aging, inflammation management, improved blood sugar metabolism, and cardiovascular disease management.

SFB® provides the following benefits: Superior source of natural antioxidants and Nrf2 activators, helps ameliorate the effects of premature aging, promotes cardiovascular health, promotes healthy brain function and mental acuity, promotes healthy vision, promotes healthy blood sugar levels, and is an excellent source of flavonoids and organic acids.

I have prepared detailed blog articles for the ingredients in SFB®. Below some of these are summarized and links to the articles are provided.

a) Cranberry Extract

Ultimate Protector+ Includes Cranberry

Ultimate Protector+ Includes Cranberry Extract

Cranberry extract is an especially good source of antioxidant polyphenols. In animal studies, the polyphenols in cranberries have been found to decrease levels of total cholesterol and so-called “bad” cholesterol. Cranberries may also inhibit the growth of tumors in human breast tissue and lower the risk of both stomach ulcers and gum disease.

Here is a list of the antioxidant and anti-inflammatory phytonutrients in found in cranberry extract.

Type of Phytonutrient Specific Molecules
Phenolic Acids hydroxybenzoic acids including vanillic acids;
—Phenolic Acids (cont.) hydroxycinnamic acids inculding caffeic,
—Phenolic Acids (cont.) coumaric, cinnamic, and ferulic acid
Proanthocyanidins epicatechin oligomers
Anthocyanins cyanidins, malvidins, and peonidins
Flavonoids quercetin, myricetin, kaempferol
Triterpenoids ursolic acid

OTHER CRANBERRY INFORMATION

    • Cranberries hold significantly high amounts of phenolic flavonoid phytochemicals called oligomeric proanthocyanidins (OPC’s). Scientific studies have shown that consumption of the berries have potential health benefits regarding cancer, aging and neurological diseases, inflammation, diabetes, and bacterial infections.
    • Antioxidant compounds in cranberry extract including OPC’s, anthocyanidin flavonoids, cyanidin, peonidin and quercetin may support cardiovascular health by counteracting against cholesterol plaque formation in the heart and blood vessels. Further, these compounds help the human body lower LDL cholesterol levels and increase HDL-good cholesterol levels in the blood.
    • Scientific studies show that cranberry juice consumption offers protection against gram-negative bacterial infections such as E.coli in the urinary system by inhibiting bacterial-attachment to the bladder and urethra.
    • It is known that cranberries turns urine acidic. This, together with the inhibition of bacterial adhesion helps prevent the formation of alkaline (calcium ammonium phosphate) stones in the urinary tract by working against proteus bacterial-infections.
    • In addition, the berries prevent plaque formation on the tooth enamel by interfering with the ability of the gram-negative bacterium, Streptococcus mutans, to stick to the surface. In this way cranberries helps prevent the development of cavities.
    • The berries are also good source of many vitamins like vitamin C, vitamin A, ß-carotene, lutein, zea-xanthin, and folate and minerals like potassium, and manganese.
  • Oxygen Radical Absorbance Capacity (ORAC) demonstrates cranberry at an ORAC score of 9584 µmol TE units per 100 g, one of the highest in the category of edible berries.

b) Pomegranate Extract

Ultimate Protector+ Includes Pomegranate

Ultimate Protector+ Includes Pomegranate

For thousands of years, the pomegranate has been extensively used as a source of food and medicine. Full of antioxidants, vitamin C and potassium, pomegranate has been used to control body weight, reduce cholesterol, fight against cell damage, and inhibit viral infections. Pomegranate extracts have anti-bacterial effects.

Pomegranates are rich in ellagic acid, gallic acid, lignans, polyphenols and other bioactive compounds, and have been shown to lower blood pressure and enhance vascular function. Furthermore, it can offset some of the negative effects of medications and chemicals. These compounds occur naturally in its peel, seeds, leaf and juice. The seeds are high in p-coumaric acid, plant sterols, tannins and fatty acids. In addition to their antihypertensive effects, they may help reduce blood sugar levels.

Pomegranate fruit is a rounded berry with a thick reddish skin covering approximately 200–1400 white to deep red or purple seeds. Pomegranate seeds are edible and hold strong antioxidant and anti-inflammatory properties due to their high content of hydrolysable tannins and anthocyanins. As compared to the antioxidant activity of vitamin E, β-carotene, and ascorbic acid, the pomegranate antioxidants appear unique due to combinations of a wide array of polyphenols, having a broader range of action against several types of free radicals. As compared to the recognized antioxidants in red wine and green tea, anthocyanins from pomegranate fruit possess significantly higher antioxidant activity.

Pomegranate has been used in various medicinal systems of medicine for the treatment and therapy of a multitude of diseases and ailments. In the ancient Indian medicinal system, i.e., in Ayurvedic medicine, the pomegranate was considered to be a whole pharmacy unto itself. It was recommended to be used as an antiparasitic agent and to treat diarrhea and ulcers. The medicinal properties of pomegranate have sparked significant interest in today’s scientific community as evidenced by the scientific research relating to health benefits of pomegranate that have been published in last few decades.

Studies have shown that pomegranate and its constituents can efficiently affect multiple signaling pathways involved in inflammation, cellular transformation, hyperproliferation, angiogenesis, initiation of tumorigenesis, and eventually suppressing the final steps of tumorigenesis and metastasis. The pomegranate constituents are shown to modulate transcription factors, pro-apoptotic proteins, anti-apoptotic proteins, cell cycle regulator molecules, protein kinases, cell adhesion molecules, pro-inflammatory mediators, and growth factors.

c) Chokeberry (Aronia)

Ultimate Protector+ Includes Chokeberry

Ultimate Protector+ Includes Chokeberry

HEALTH BENEFITS OF CHOKEBERRY (ARONIA)

Aronia melanocarpa (black chokeberry) has attracted scientific interest due to its deep purple, almost black pigmentation that arises from dense contents of polyphenols, especially anthocyanins. Total polyphenol content is 1752 mg per 100 g in fresh berries, anthocyanin content is 1480 mg per 100 g, and proanthocyanidin concentration is 664 mg per 100 g. These values are among the highest measured in plants to date.

The plant produces these pigments mainly in the leaves and skin of the berries to protect the pulp and seeds from constant exposure to ultraviolet radiation and production of free radicals. By absorbing UV rays in the blue-purple spectrum, leaf and skin pigments filter intense sunlight, serve antioxidant functions and thereby have a role assuring regeneration of the species.

Analysis of polyphenols in chokeberries has identified the following individual chemicals (among hundreds known to exist in the plant kingdom): cyanidin-3-galactoside, cyanidin-3-arabinoside, quercetin-3-glycoside, epicatechin, caffeic acid, delphinidin, petunidin, pelargonidin, peonidin, and malvidin.All these except caffeic acid are members of the flavonoid category of phenolics.

In a standard measurement of antioxidant strength, the oxygen radical absorbance capacity or ORAC, demonstrates aronia to have one of the highest values yet recorded for a fruit — 16,062 micro moles of Trolox Eq. per 100 g. The components contributing to this high measurement were both anthocyanins and proanthocyanidins, with the proanthocyanidin level “among the highest in foods”, which may explain their potent astringent taste.

d) Goji Berry

Ultimate Protector+ Includes Goji Berry

Ultimate Protector+ Includes Goji Berry

Goji Berries contain abundant polysaccharides (LBPs, comprising 5%–8% of the dried fruits), scopoletin (6-methoxy-7-hydroxycoumarin, also named chrysatropic acid, ecopoletin, gelseminic acid, and scopoletol), the glucosylated precursor, and stable vitamin C analog 2-O-β-D-glucopyranosyl-L-ascorbic acid, carotenoids (zeaxanthin and β-carotene), betaine, cerebroside, β-sitosterol, flavonoids, amino acids, minerals, and vitamins (in particular, riboflavin, thiamin, and ascorbic acid).

The predominant carotenoid is zeaxanthin, which exists mainly as dipalmitate (also called physalien or physalin). The content of vitamin C (up to 42 mg/100 g) in goji berry (also known as wolfberry) is comparable to that of fresh lemon fruits. As to the seeds, they contain zeaxanthin (83%), β-cryptoxanthin (7%), β-carotene (0.9%), and mutatoxanthin (1.4%), as well as some minor carotenoids.

In fact, increasing lines of experimental studies have revealed that L. barbarum berries have a wide array of pharmacological activities, which is thought to be mainly due to its high LBPs content. Water-soluble LBPs are obtained using an extraction process that removes the lipid soluble components such as zeaxanthin and other carotenoids with alcohol. LBPs are estimated to comprise 5%–8% of LBFs and have a molecular weight ranging from 24 kDa to 241 kDa. LBPs consist of a complex mixture of highly branched and only partly characterized polysaccharides and proteoglycans.

The glycosidic part accounts, in most cases, for about 90%–95% of the mass and consists of arabinose, glucose, galactose, mannose, rhamnose, xylose, and galacturonic acid. LBPs are considered the most important functional constituents in LBFs. Different fractions of LBPs have different activities and the galacturonic acid content is an imperative factor for activities of LBP. The bioactivities of polysaccharides are often in reverse proportion with their molecular weights. Increasing lines of evidence from both preclinical and clinical studies support the medicinal, therapeutic, and health-promoting effects of LBPs.

e) Mangosteen

Ultimate Protector+ Includes Mangosteen

Ultimate Protector+ Includes Mangosteen

The Mangosteen extract in Ultimate Protector+ has been extracted with non-GMO food grade ethanol and distilled water. Testing has indicated the product contains over 10% polyphenols.

Mangosteen extract in obtained from the skin and whole fruit for which numerous biological activities have been reported including: antimutagenic, antibacterial, hypocholesterolemic, antioxidant, and protective against tumorigenesis.

Mangosteen contains nutrients with antioxidant capacity, such as vitamin C and folate. Plus, it provides xanthones — a unique type of plant compound known to have strong antioxidant properties. In several test-tube and animal studies, the antioxidant activity of xanthones has resulted in anti-inflammatory, anticancer, anti-aging, heart protective, and antidiabetic effects.

Additionally, some research suggests that certain plant compounds in mangosteen may have antibacterial properties — which could benefit your immune health by combating potentially harmful bacteria. In a 30-day study in 59 people, those taking a mangosteen-containing supplement experienced reduced markers of inflammation and significantly greater increases in healthy immune cell numbers compared to those taking a placebo.

f) Apple Extract

Ultimate Protector+ Includes Apple

Apples contain a large concentration of flavonoids, as well as a variety of other phytochemicals, and the concentration of these phytochemicals may depend on many factors, such as cultivar of the apple, harvest and storage of the apples, and processing of the apples. The concentration of phytochemicals also varies greatly between the apple peels and the apple flesh.

Some of the most well studied antioxidant compounds in apples include quercetin-3-galactoside, quercetin-3-glucoside, quercetin-3-rhamnoside, catechin, epicatechin, procyanidin, cyanidin-3-galactoside, coumaric acid, chlorogenic acid, gallic acid, and phloridzin. Recently researchers have examined the average concentrations of the major phenolic compounds in six cultivars of apples. They found that the average phenolic concentrations among the six cultivars were: quercetin glycosides, 13.2 mg/100 g fruit; vitamin C, 12.8 mg/100 g fruit; procyanidin B, 9.35 mg/100 g fruit; chlorogenic acid, 9.02 mg/100 g fruit; epicatechin, 8.65 mg/100 g fruit; and phloretin glycosides, 5.59 mg/100 g fruit.

The compounds most commonly found in apple peels consist of the procyanidins, catechin, epicatechin, chlorogenic acid, phloridzin, and the quercetin conjugates. In the apple flesh, there is some catechin, procyanidin, epicatechin, and phloridzin, but these compounds are found in much lower concentrations than in the peels. Quercetin conjugates are found exclusively in the peel of the apples. Chlorogenic acid tends to be higher in the flesh than in the peel.

Because the apple peels contain more antioxidant compounds, especially quercetin, apple peels may have higher antioxidant activity and higher bioactivity than the apple flesh. Research showed that apples without the peels had less antioxidant activity than apples with the peels. Apples with the peels were also better able to inhibit cancer cell proliferation when compared to apples without the peels. More recent work has shown that apple peels contain anywhere from two to six times (depending on the variety) more phenolic compounds than in the flesh, and two to three times more flavonoids in the peels when compared to the flesh. The antioxidant activity of these peels was also much greater, ranging from two to six times greater in the peels when compared to the flesh, depending on the variety of the apple. This work is supported a study which found that rats consuming apple peels showed greater inhibition of lipid peroxidation and greater plasma antioxidant capacity when compared to rats fed apple flesh.

Many of these phytochemicals from apples have been widely studied, and many potential health benefits have been attributed to these specific phytochemicals. The procyanidins, epicatechin and catechin, have strong antioxidant activity and have been found to inhibit low density lipoprotein (LDL) oxidation in vitro. In mice, catechin inhibits intestinal tumor formation and delays tumors onset. One study found that chlorogenic acid has very high alkyl peroxyl radical (ROO•) scavenging activity. Compared to about 18 other antioxidant compounds (including quercetin, gallic acid, α-tocopherol), chlorogenic was second only to rutin. Since ROO• may enhance tumor promotion and carcinogenesis, chlorogenic acid may add to the protective effect of apples against cancer. Chlorogenic acid has been found to inhibit 8-dehydroxy-deoxyguanosine formation in cellular DNA in a rat model following treatment with 4-nitroquinoline-1-oxide.

Quercetin is also a strong antioxidant, and is thought to have potential protective effects against both cancer and heart disease. Briefly, quercetin has been found to down regulate expression of mutant p53 in breast cancer cells, arrest human leukemic T-cells in G1, inhibit tyrosine kinase, and inhibit heat shock proteins. Quercetin has protected Caco-2 cells from lipid peroxidation induced by hydrogen peroxide and Fe2+. In mice liver treated with ethanol, quercetin decreased lipid oxidation and increased glutathione, protecting the liver from oxidative damage. Recently, it has been found that high doses of quercetin inhibit cell proliferation in colon carcinoma cell lines and in mammary adenocarcinoma cell lines, but at low doses quercetin increased cell proliferation (20% in colon cancer cells and 100% in breast cancer cells). However, low doses of quercetin (10 uM) inhibited cell proliferation in Mol-4 Human Leukemia cells and also induced apoptosis. Quercetin inhibited intestinal tumor growth in mice, but not in rats. Low levels of quercetin inhibited platelet aggregation, calcium mobilization, and tyrosine protein phosphorylation in platelets. Modulation of platelet activity may help prevent cardiovascular disease.

g) Blueberry and Bilberry Extract

wild bilberry and wild blueberry
Wild bilberry and wild blueberry provide Nrf2 activators.

The key compounds in bilberry fruit are called anthocyanins and anthocyanosides. These compounds help build strong blood vessels and improve circulation to all areas of the body. They also prevent blood platelets from clumping together (helping to reduce the risk of blood clots), and they have antioxidant properties (preventing or reducing damage to cells from free radicals). Anthocyanins boost the production of rhodopsin, a pigment that improves night vision and helps the eye adapt to light changes.

Bilberry fruit is also rich in tannins, a substance that acts as an astringent. The tannins have anti-inflammatory properties and may help control diarrhea.

Bilberries have been shown to have the highest Oxygen Radical Absorbance Capacity (ORAC) rating of more than 20 fresh fruits and berries. The antioxidant properties of bilberries were shown to be even stronger than those of cranberries, raspberries, strawberries, plums, or cultivated blueberries.

The antioxidant powers and health benefits of bilberries and blueberries can be attributed to a number of remarkable compounds contained in them, including the following:

  • Anthocyanins
    • malvidins
    • delphinidins
    • pelargonidins
    • cyanidins
    • peonidins
  • Hydroxycinnamic acids
    • caffeic acids
    • ferulic acids
    • coumaric acids
  • Hydroxybenzoic acids
    • gallic acids
    • procatchuic acids
  • Flavonols
    • kaempferol
    • quercetin
    • myricetin
  • Other phenol-related phytonutrients
    • pterostilbene
    • resveratrol
  • Other nutrients
    • lutein
    • zeaxanthin
    • Vitamin K
    • Vitamin C
    • manganese

2) Curcumin

Ultimate Protector+ Includes Curcumin

Ultimate Protector+ Includes Curcumin

We have included Curcumin (95% curcuminoids in ULTIMATE PROTECTOR™. This ingredient contains three main chemical compounds – Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin – collectively known as Curcuminoids and all derived from Turmeric. Curcumin has been shown to be one of the most potent Nrf2 transcription factor activators. Studies have reported that curcumin and turmeric protect the liver against several toxicants both in vitro and in vivo. A number of reports showed the curative action of turmeric and curcuminoids. Curcumin is a potent scavenger of free radicals such as superoxide anion radicals, hydroxyl radicals, and nitrogen dioxide radicals. It exerts powerful antioxidant and anti-inflammatory properties.


3) Trans-Resveratrol (98% from Polygonum cuspidatum – giant knotweed)

giant knotweed resveratrol

Knotweed (Polygonum cuspidatum) is a major source for resveratrol.

Trans-resveratrol provides antioxidant protection, boosts cellular energy, and balances the immune system. It has been proven in studies to activate the SIRT1 longevity gene and enhance cellular productivity. Several research studies have shown that trans-resveratrol activates Nrf2 transcription factor, significantly modulates biomarkers of bone metabolism, inhibits pro-inflammatory enzymes such as COX-1 and COX-2, and exhibits cardioprotective effects, neuroprotective properties, and caloric restrictive behavior. Trans-resveratrol has shown the ability to increase the number of mitochondria thereby increasing total daily energy. Studies have shown that trans-resveratrol promotes an increase in mitochondrial function. Increased mitochondrial function translates into an increase in energy availability, improved aerobic capacity, and enhanced sensorimotor function. Trans-resveratrol has an ORAC value of 31,000 µmole TE/g.


4) Green Tea Extract

Ultimate Protector+ Includes Green Tea Extract

Ultimate Protector+ Includes Green Tea Extract

Green Tea Extract contains highly bioavailable bioflavonoid complexes that in research studies have been shown to have powerful antioxidant capability. Green tea extract is obtained from the unfermented leaves of Camellia sinensis for which numerous biological activities have been reported including: cell protective, antimicrobial, and antioxidant. The green tea extract in Ultimate Protector is extracted is extracted by non-GMO ethanol and distilled water and contains ~ 90% polyphenols and 50% epigallocatechingallate (EGCG).

Epigallocatechin gallate (EGCG) is the most abundant catechin compound in green tea. It is well established that EGCG is a potent antioxidant and anti-inflammatory agent. Epidemiological studies show that consumption of 100 or more mg of EGCG per day is beneficial, as it is the most potent Nrf2 activator among all green tea catechins. EGCG exhibits robust diffusion through bodily tissues, including the endothelium of the blood brain barrier.

EGCG has the capacity to activate Nrf2/ARE and induce Heme oxygenase-1 (HO-1) expression. Several studies have shown that EGCG can also interact with kinases, causing the disassociation of Nrf2/Keap1 complex.

Protective effects of EGCG have been reported against ischemia/reperfusion injury. Administration of EGCG showed improved neurologic scores, reduced infarct volume, and ameliorated neuronal apoptosis due to increased GSH biosynthesis (via Nrf2 activation) and decreased ROS content. By inducing the expression of Nrf2 and HO-1, EGCG increases important endogenous antioxidants in microglial cells.

5) VinCare® whole grape extract (seed, pulp, and skin)

Ultimate Protector+ Includes Whole Grape Extract

Ultimate Protector+ Includes Whole Grape Extract

Whole Grape Extract contains highly bioavailable bioflavonoid complexes that in research studies have been shown to have powerful antioxidant capability. The Oligomeric Proanthocyanidins (OPCs) in grape extract are able to strengthen collagen fibers in aging or damaged connective tissue and can act as a preventative against connective tissue degradation. Some research indicates that anthocyanidins, which are found in extracts of grape seed, skin, and stems (but not in grape seed extract), can reduce oxidized glutathione while at the same time become reduced themselves. In addition, extracts of grape skin and pulp (but not those of grape seed extract) contain trans-resveratrol that has been shown to have cell protective effects.

Grape seed extract has been reported to demonstrate a remarkable spectrum of biological, pharmacological and therapeutic properties against oxidative stress. The antioxidative activities of grape seed extract have been found to be much stronger than those of vitamins C and E. Studies have indicated that grape seed extract showed a protective effect on cardiovascular disease, nephropathy, atherosclerosis, and neuropathy, among other conditions.

Vincare® contains ~80% polypnenols and has an ORAC value of about 19,000 µmole TE/g. ORAC 5.0 testing of grape seed extract exhibits one of the highest values of any tested material at about 100,000 µmole TE/g.

It has been shown that grape seed OPCs activate nuclear erythroid2-related factor2 (Nrf2), which is a key antioxidative transcription factor, with the concomitant elevation of downstream hemeoxygenase-1 (HO-1). Click here to view an excellent article entitled Proanthocyanidins [OPCs] against Oxidative Stress: From Molecular Mechanisms to Clinical Applications.

7) Bioperine®:

Bioperine® is a black pepper extract that has been shown to enhance the absorption of nutrients by 30–60 percent and makes all of the nutrients in this product more effective.

Ultimate Protector+™ will be most effective when used in conjunction with other foundational nutritional supplements that support the body’s metabolism, including Multi Two or Mighty Multi-Vite!™ (therapeutic multivitamin formulas), Omega Plus (essential fatty acids with Vitamin E), PRO-C™ (antioxidant formula), and one of our high-RNA Rejuvenate!™ superfoods.

COMPOSITION: six veggie capsules provides the following percentages of the Daily Value:

Serving Size: 6 Veggie Capsules Servings per Container: 30
Amount Per Serving Amounts % Daily Value
Vitamin C (as 100% USP-grade, non-GMO ascorbic acid) 1,500 mg 1667%
Calcium (from calcium malate) 60 mg 6
Magnesium (from magnesium malate) 60 mg 15
SFB®† (50% polyphenols, Orac: 9,000 units/gm) 180 mg *
Curcumin (95% min. curcuminoids from Curcuma longa) (root) 135 mg *
Green Tea extract (92% polyphenols, 50% EGCG) 135 mg *
Trans-Resveratrol 98% 135 mg *
Vincare®† whole grape extract (80% polyphenols, Orac: 19,000 units/gm) 135 mg *
Bioperine®†† 7.5 mg *
*
* Daily Value not established

Other ingredients: vegetarian capsule (veggie cap), microcrystalline cellulose, silica, and ascorbyl palmitate.

Directions for Use: As a dietary supplement take two capsules three times daily with food, or as directed by a health care professional.

ULTIMATE PROTECTOR Does Not Contain: wheat, rye, oats, barley, corn, gluten, soy, egg, dairy, yeast, sugar, shellfish, GMOs, wax, preservatives, colorings, or artificial flavorings.

ULTIMATE PROTECTOR+™ will be most effective when used in conjunction with other foundational nutritional supplements that support the body’s metabolism, including Multi Two or Mighty Multi-Vite!™ (therapeutic multivitamin formulas), Essential Fats plus E (essential fatty acids with Vitamin E), PRO-C™ (antioxidant formula), and one of our high-RNA Rejuvenate!™ superfoods.

†SFB® and VinCare® are registered trademark of Ethical Naturals, Inc.

†† Bioperine® is a registered trademark of Sabinsa Corporation.

ADDITIONAL RESOURCES

New Directions for Preventing Free-Radical Damage

Natural Phytochemical Nrf2 Activators for Chemoprevention

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ULTIMATE PROTECTOR+ INGREDIENTS – GOJI BERRY

Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicist wild bilberry and wild blueberry Ultimate Protector+ includes goji berry extract (also known as wild fresh goji berry fruit powder extract and wolfberry extract), as well as extracts from 12 different fruits, vegetables, and herbs. Each of these ingredients contain substances that may be considered to be polyphenols, antioxidants, and Nrf2 activators. In this article, I will explore the ingredient goji berry (Lycium barbarum) extract which is a component of SFB® – Standardized Fruit Blend from Ethical Naturals, Inc.

Ultimate Protector+ Includes Goji Berry

Ultimate Protector+ Includes Goji Berry

SFB® is a proprietary formula that combines extracts from Grape, Cranberry, Pomegranate, Blueberry, Apple, Mangosteen, Bilberry, Chokeberry, and Goji Berry. It is high in fruit polyphenols, flavonoids, anthocyanins, catechins, proanthocyanins, ellagic acid, xanthines, chlorogenic acid, pterostilbenes, resveratrol, phloridzin, quercetin, zeaxanthin, carotinoids, polysaccharides, quinic acid, and more. With its diverse blend, SFB® offers over 40-50% polyphenols as well as >9,000 ORAC units in a single gram.

Polyphenols, anthocyanins, and other plant elements are powerful ingredients associated with a variety of areas of human health, including healthy aging, healthy glucose metabolism, cardiovascular health, and inflammation management.

HEALTH BENEFITS OF GOJI BERRY

The Goji Berry extract in Ultimate Protector+ is non-GMO and has been extracted with  water. Testing has indicated the product contains over 1.5% polyphenols. In numerous epidemiological studies, goji berries have been associated with a decreased risk of chronic diseases such as cardiovascular disease, cancer, and asthma.

CHEMICAL COMPOSITION OF GOJI BERRIES

Goji Berries contain abundant polysaccharides (LBPs, comprising 5%–8% of the dried fruits), scopoletin (6-methoxy-7-hydroxycoumarin, also named chrysatropic acid, ecopoletin, gelseminic acid, and scopoletol), the glucosylated precursor, and stable vitamin C analog 2-O-β-D-glucopyranosyl-L-ascorbic acid, carotenoids (zeaxanthin and β-carotene), betaine, cerebroside, β-sitosterol, flavonoids, amino acids, minerals, and vitamins (in particular, riboflavin, thiamin, and ascorbic acid).

The predominant carotenoid is zeaxanthin, which exists mainly as dipalmitate (also called physalien or physalin). The content of vitamin C (up to 42 mg/100 g) in goji berry (also known as wolfberry) is comparable to that of fresh lemon fruits. As to the seeds, they contain zeaxanthin (83%), β-cryptoxanthin (7%), β-carotene (0.9%), and mutatoxanthin (1.4%), as well as some minor carotenoids.

In fact, increasing lines of experimental studies have revealed that L. barbarum berries have a wide array of pharmacological activities, which is thought to be mainly due to its high LBPs content. Water-soluble LBPs are obtained using an extraction process that removes the lipid soluble components such as zeaxanthin and other carotenoids with alcohol. LBPs are estimated to comprise 5%–8% of LBFs and have a molecular weight ranging from 24 kDa to 241 kDa. LBPs consist of a complex mixture of highly branched and only partly characterized polysaccharides and proteoglycans.

The glycosidic part accounts, in most cases, for about 90%–95% of the mass and consists of arabinose, glucose, galactose, mannose, rhamnose, xylose, and galacturonic acid. LBPs are considered the most important functional constituents in LBFs. Different fractions of LBPs have different activities and the galacturonic acid content is an imperative factor for activities of LBP. The bioactivities of polysaccharides are often in reverse proportion with their molecular weights. Increasing lines of evidence from both preclinical and clinical studies support the medicinal, therapeutic, and health-promoting effects of LBPs.

Scientific Studies on the Antioxidant Effects of GOJI BERRIES

Databases of scientific studies (like the National Institutes of Health (NIH) PubMed database) contain numerous of up-to-date studies and abstracts about goji berries.

Below we provide a few relevant scientific studies on the health benefits of goji berries.

Goji Berries as a Potential Natural Antioxidant Medicine: An Insight into Their Molecular Mechanisms of Action.

Oxid Med Cell Longev. 2019 Jan 9;2019:2437397. doi: 10.1155/2019/2437397. eCollection 2019.
Authors: Ma ZF, Zhang H, Teh SS, Wang CW, Zhang Y, Hayford F, Wang L, Ma T, Dong Z, Zhang Y, Zhu Y1
From: https://www.ncbi.nlm.nih.gov/pubmed/30728882

Abstract

Goji berries (Lycium fruits) are usually found in Asia, particularly in northwest regions of China. Traditionally, dried goji berries are cooked before they are consumed. They are commonly used in Chinese soups and as herbal tea. Moreover, goji berries are used for the production of tincture, wine, and juice. Goji berries are high antioxidant potential fruits which alleviate oxidative stress to confer many health protective benefits such as preventing free radicals from damaging DNA, lipids, and proteins. Therefore, the aim of the review was to focus on the bioactive compounds and pharmacological properties of goji berries including their molecular mechanisms of action. The health benefits of goji berries include enhancing hemopoiesis, antiradiation, antiaging, anticancer, improvement of immunity, and antioxidation. There is a better protection through synergistic and additive effects in fruits and herbal products from a complex mixture of phytochemicals when compared to one single phytochemical.

An evidence-based update on the pharmacological activities and possible molecular targets of Lycium barbarum polysaccharides

Drug Des Devel Ther. 2015; 9: 33–78.
Authors: Jiang Cheng, Zhi-Wei Zhou, Hui-Ping Sheng, Lan-Jie He, Xue-Wen Fan, Zhi-Xu He, Tao Sun, Xueji Zhang, Ruan Jin Zhao, Ling Gu, Chuanhai Cao,  and Shu-Feng Zhou
From: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277126/

Abstract

Lycium barbarum berries, also named wolfberry, Fructus lycii, and Goji berries, have been used in China and other Asian countries for more than 2,000 years as a traditional medicinal herb and food supplement. L. barbarum polysaccharides (LBPs) are the primary active components of L. barbarum berries and have been reported to possess a wide array of pharmacological activities. Herein, we update our knowledge on the main pharmacological activities and possible molecular targets of LBPs. Several clinical studies in healthy subjects show that consumption of wolfberry juice improves general wellbeing and immune functions. LBPs are reported to have antioxidative and antiaging properties in different models. LBPs show antitumor activities against various types of cancer cells and inhibit tumor growth in nude mice through induction of apoptosis and cell cycle arrest. LBPs may potentiate the efficacy of lymphokine activated killer/interleukin-2 combination therapy in cancer patients. LBPs exhibit significant hypoglycemic effects and insulin-sensitizing activity by increasing glucose metabolism and insulin secretion and promoting pancreatic β-cell proliferation. They protect retinal ganglion cells in experimental models of glaucoma. LBPs protect the liver from injuries due to exposure to toxic chemicals or other insults. They also show potent immunoenhancing activities in vitro and in vivo. Furthermore, LBPs protect against neuronal injury and loss induced by β-amyloid peptide, glutamate excitotoxicity, ischemic/reperfusion, and other neurotoxic insults. LBPs ameliorate the symptoms of mice with Alzheimer’s disease and enhance neurogenesis in the hippocampus and subventricular zone, improving learning and memory abilities. They reduce irradiation- or chemotherapy-induced organ toxicities. LBPs are beneficial to male reproduction by increasing the quality, quantity, and motility of sperm, improving sexual performance, and protecting the testis against toxic insults. Moreover, LBPs exhibit hypolipidemic, cardioprotective, antiviral, and antiinflammatory activities. There is increasing evidence from preclinical and clinical studies supporting the therapeutic and health-promoting effects of LBPs, but further mechanistic and clinical studies are warranted to establish the dose–response relationships and safety profiles of LBPs.

Biological activities and potential health benefit effects of polysaccharides isolated from Lycium barbarum L.

2013 Mar;54:16-23. doi: 10.1016/j.ijbiomac.2012.11.023. Epub 2012 Nov 28.
Jin M1, Huang Q, Zhao K, Shang P.
From: https://www.ncbi.nlm.nih.gov/pubmed/23200976

Abstract

Recently, isolation and investigation of novel ingredients with biological activities and health benefit effects from natural resources have attracted a great deal of attention. The fruit of Lycium barbarum L., a well-known Chinese herbal medicine as well as valuable nourishing tonic, has been used historically as antipyretic, anti-inflammation and anti-senile agent for thousands of years. Modern pharmacological experiments have proved that polysaccharide is one of the major ingredients responsible for those biological activities in L. barbarum. It has been demonstrated that L. barbarum polysaccharides had various important biological activities, such as antioxidant, immunomodulation, antitumor, neuroprotection, radioprotection, anti-diabetes, hepatoprotection, anti-osteoporosis and antifatigue. The purpose of the present review is to summarize previous and current references regarding biological activities as well as potential health benefits of L. barbarum polysaccharides.

Goji (Lycium barbarum and L. chinense): Phytochemistry, Pharmacology and Safety in the Perspective of Traditional Uses and Recent Popularity

Planta Med 2010; 76(1): 7-19
Author: Olivier Potterat
From: https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0029-1186218#AT0541-1

Abstract

Since the beginning of this century, Goji berries and juice are being sold as health food products in western countries and praised in advertisements and in the media for well-being and as an anti-aging remedy. The popularity of Goji products has rapidly grown over the last years thanks to efficient marketing strategies. Goji is a relatively new name given to Lycium barbarum and L. chinense, two close species with a long tradition of use as medicinal and food plants in East Asia, in particular in China. While only L. barbarum is officinal, the fruit (fructus Lycii) and the root bark (cortex Lycii radicis) of both species are used in the folk medicine. We review here the constituents, pharmacology, safety, and uses of L. barbarum and L. chinensewith consideration to the different parts of the plant. Investigations of the fruit have focused on proteoglycans, known as “Lycium barbarum polysaccharides”, which showed antioxidative properties and some interesting pharmacological activities in the context of age related diseases such as atherosclerosis and diabetes. As to the root bark, several compounds have demonstrated a hepatoprotective action as well as inhibitory effects on the rennin/angiotensin system which may support the traditional use for the treatment of hypertension. While there are no signs of toxicity of this plant, two cases of possible interaction with warfarin point to a potential risk of drug interaction. In view of the available pharmacological data and the long tradition of use in the traditional Chinese medicine, L. barbarum and L. chinense certainly deserve further investigation. However, clinical evidences and rigorous procedures for quality control are indispensable before any recommendation of use can be made for Goji products.

GOJI BERRIES SUMMARY

Goji Berries are an important fruit full of polyphenols, antioxidants, polysaccharides (LBPs), carotenoids, and Nrf2 activators that help to make Ultimate Protector+ such an outstanding nutritional supplement.

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ESSENTIAL NUTRIENTS – SEVEN ARGUMENTS FOR NUTRITIONAL SUPPLEMENTS

Fred Liers PhD nutrients nutritional supplementsAlmost daily articles, reports, or studies appear claiming nutritional supplements are not effective. The claims vary, but the verdict is always there is little or no scientific evidence proving supplements (or the nutrients in supplements) work. Others assert that people who take supplements have the world’s most expensive urine. This is nonsense! The scientific evidence is clear, available, and it has been for a long time.

Among the many problems with these reports is bashing supplements based on studies using low dose or non-therapeutic levels of nutrients. There is frequently failure to consider the importance of synergy among nutrients. Often there is data manipulation via statistical methods (often in meta-analyses).

Well beyond the question of whether supplements support health are the factors in modern life that create a greater needs for supplementing with important vitamins, minerals, cofactors, and other nutrients.

This month we present “Seven Arguments for Nutritional Supplements.” As the title implies, there are at least seven solid arguments for nutritional supplementation. There are actually a lot more.

To preview these arguments in favor of taking supplements, they are: 1) reduced food quality, 2) nutrient density varies by location, 3) modern lifestyles and stress, 4) environmental pollution, 5) too low RDAs, and 6) promotion of health and delaying of aging, and 7) the human right to correct information.

essential nutrients fatty acids EFA supplement

Essential Fatty Acids (EFA) are one type of essential nutrient required for health.

We at HPDI re-publish articles from the Orthomolecular News Service  (OMNS) because the authors provide much needed truth. Truth the form of correcting the false assumptions of anti-supplement propagandists to clarify the benefits of nutritional supplements. This information can help people be healthier easily and at relatively low cost.

HPDI offers a full line of foundational nutritional supplements, including multivitamins, vitamin C and antioxidant formulas, essential fats, and high-RNA Rejuvenate! superfoods. We also offer nearly 100 other nutritional supplements from single nutrients to condition specific formulas. See our full product overview.

Enjoy this article from the Orthomolecular News Service (OMNS). ~

Seven Arguments for Taking Nutritional Supplements

by Dag Viljen Poleszynski, PhD

(OMNS Sept 12 2018)

One of the most vitamin-restrictive countries in the world is Norway. There, authorities limit potencies to only slightly higher than RDA (Recommended Dietary Allowance) levels for dietary supplements sold outside of pharmacies. The traditional reasoning is that most people receive the nutrients they need from a “balanced diet.” [1]

The authorities are also obsessively concerned that some vitamins and minerals are harmful in high doses. And, since an intake of water-soluble vitamins in excess of needs is excreted in the urine, Norwegian “experts” advise that taking supplements is a waste of money.

Accordingly, the argument goes, the public should be protected not only from possible harm, but also from wasting money on unnecessary nutrients. The official policies on nutritional supplements vary within OECD (Organization for Economic Cooperation and Development) countries. Some are more liberal, while others are even more restrictive.

The official view on the connection between nutrient intake and possible toxicity is illustrated by the Norwegian Food Authority in a graph. [2]

Perceived risk from intake of nutrients. (Source: Expert Group on Vitamins and Minerals. Safe upper limits for Vitamins and Minerals. May 2003: Food Standards Agency, UK.)

The graph illustrates the official view on nutrients, assuming that nutrients function in the same way as pharmaceuticals, which they do not. Supplements of most vitamins, but also minerals and other nutrients, do not have very serious side effects even when taken at very high levels – in contrast with most drugs. [3,4] The fact that most of the chemotherapeutic drugs used against cancer have none or even just marginal effects against most cancers [5], while at the same time cause a lot of serious side effects, is rarely up for discussion.

The idea that nutritional supplements are not safe has a legal underpinning in Norwegian Food Law, which in section 16 prohibits sale of any food which is not safe: “Any food shall be considered not to be safe if it is seen as detrimental to health or not fit for consumption.” [6]

However, the Norwegian authorities do admit that vitamin D supplements are needed during part of the year. [1] Only part of the year? One third of Norway is within the Arctic Circle. Norway has far too little sunshine (especially during winter months) to get adequate levels of vitamin D from UVB radiation on the skin.

The authorities also recommend that pregnant women take folic acid to prevent birth defects, and omega-3-fatty acids may be advisable for those who do not eat fish regularly. Norwegians have a long tradition of giving children cod liver oil, which in a daily tablespoon provides enough vitamin A and D and essential fatty acids to cover basic needs.

Essential and conditionally essential nutrients

There are thousands of dietary supplements on the market, including 40+ essential nutrients alone and in various combinations, i.e. vitamins, minerals, trace elements and fatty acids. However, a number of other nutrients are “conditionally essential”, meaning that the body normally can make these molecules, but some people do not make optimal amounts. Examples are L-carnitine, alpha-lipoic acid, the methyl donor betaine, [7] chondroitin sulfate, coenzyme Q10, choline, amino acids such as tyrosine or arginine, and “essential” sugars normally formed in the body. [8]

Healthy young people normally make sufficient amounts of conditionally essential molecules in the body, although the levels are not always optimal. With inadequate levels of minerals or vitamins, key enzymes in biochemical pathways may not function optimally.

Due to genetic mutations, some enzymes may have increased needs for certain cofactors (vitamins), which can prevent them from functioning optimally.[9] Some enzymes only function normally when supplied with cofactors in greater amounts than normally required.

If supplements of essential nutrients prove insufficient for optimal enzyme function, “conditionally essential” nutrients may be added as part of a comprehensive, therapeutic program.

Some reservations

Parents are advised to become familiar with the literature on essential nutrients, for instance by consulting the Orthomolecular News Service. Children should be given supplements in appropriate doses and in a suitable form. Pills should not be given before children can control the swallowing reflex. Multivitamin powder can be given dissolved in water or juice. Parents should not dose vitamin C so high that a child comes to school or kindergarten with loose bowels or diarrhea.

In high doses, niacin may cause unpleasant side effects such as flushing and itching lasting up to several hours. [10] Although this is not dangerous, it may cause a child to feel unwell and anxious. Starting niacin supplementation with a low dose and gradually increasing it will allow the body to adapt and avoid the niacin flush.

A multivitamin supplement containing moderate amounts of niacin is often adequate until a child is 8-10 years old. For younger children, the dosage should start with only a few tens of milligrams, and not increased to more than 50-100 mg/day. Adults may gradually get used to taking 1,000-1,500 mg/d divided into 3 doses per day.

When it comes to omega-3 fatty acids (omega = ω) such as EPA and DHA, children may be given cod liver oil and served fish and/or other seafood 2-3 times a week. It is important to check the dose of vitamin A supplied, as it can be toxic in high doses, especially for children. One problem with cod liver oil today is that vitamin D has been removed during processing, thus changing the natural ratio of the two vitamins so that we ingest relatively too much of vitamin A. [11]

Higher dosages may be given after having consulted a therapist who has measured the ratio of omega-6 to omega-3 fatty acids in relevant cell membranes (red blood cells). In most industrialized countries, many people get too much of the omega-6 fatty acids, and would therefore benefit from eating more seafood or taking supplements with omega-3 fatty acids derived from organisms low in the food chain (algae, krill).

Flax seeds contain a high level of the essential omega-3 fatty acid alpha-linolenic acid, and freshly ground flaxseed meal or flax oil can be mixed with breakfast cereals or smoothies. Note that it may be advisable to limit eating farmed fish to once per week, since their fodder contains less omega-3 fatty acids than the food eaten by wild fish, and possibly also contains more contaminants. [12] Some researchers even warn against letting children eat too much fish because of the content of environmental toxins. [13,14]

Reasons for high-dose supplements of micronutrients

I have identified a number of arguments in favor of supplementing the modern diet with essential nutrients, here summarized with seven headlines. Most people should consider taking a multivitamin supplement containing vitamins and minerals even if they eat a nutritionally balanced diet.

Additional nutrients may contribute to better health and, in some cases, can be of vital importance in our modern world. The arguments are presented in random order, i.e. the order does not reflect priority.

1. The agricultural revolution has reduced food quality

The transition from an existence as hunter and gatherers to urban agriculture around 10,000 years ago began an epoch when foods were mass-produced but had lower nutritional density, compared with the previous food eaten by our ancestors. The nutritional density in many foods has fallen significantly since human societies transformed from hunter-gatherers into resident farmers. This is especially true in the last 60-70 years after agriculture was changed from small, versatile ecologically driven family farms to large, chemical-based, industrial agriculture. [15]

The reduction of nutritional content in modern crops, compared with older varieties, is well documented. [16] It is a consequence of soil erosion, loss of essential minerals from continual heavy use, combined with breeding of new varieties, which has increased the size and growth rate of plants by increasing the content of sugar and water and decreasing their mineral content compared to ancient species. At the same time, the relative content of other macronutrients (fat, protein/amino acids) and antioxidants may have been reduced.

Reduced nutritional density in many foods, combined with the use of refined “foods” like sugar, white flour and refined oils, places a greater priority on eating the most nutritious foods.

Farm produce grown organically generally has higher levels of essential nutrients such as trace minerals because the soil contains higher levels of trace minerals and the produce grows slower and thus has more time to absorb nutrients from the soil. Examples of nutrient dense foods are sardines, wild salmon, shellfish, eggs, liver, kale, collards and spinach, sea plants (seaweed), garlic, blueberries, and dark chocolate. [17]

2. Nutritional content of food varies with geographical location

Nutritional density varies considerably geographically between different regions, even with the same agricultural methods. This was documented in the United States in 1948 by a researcher at Rutgers University in the so-called Firman Bear report. [18] At that time agriculture was little mechanized, and artificial fertilizers and pesticides were hardly used.

The analysis found large differences in the content of minerals in the same food. The largest variations were found for potassium, sodium, boron and iron in spinach, while the greatest differences in calcium, magnesium and copper content were found in tomatoes.

The soil in areas with relatively low rainfall may in some cases contain an extremely high concentration of minerals, which is reflected in the plants growing there. This was well documented 70 years ago in the book Tomorrow’s Food. [19] The dentist George W. Heard found that the soil in Hereford, Texas, was exceptionally rich in minerals.[20]

Hereford became known as the “town without a toothache” after a newspaper article from January 29, 1942, reported that Hereford had the lowest incidence of tooth decay of any city in the United States. [21] Dr. Heard found that people in Hereford had exceptionally few dental cavities and also that the soil locally was especially rich in minerals. He emphasized that the population in the county ate unprocessed food and was drinking raw milk. [19]

Recent research shows that differences in the content of the selenium in the soil can cause major differences in the concentration of selenium in meat. [22] For instance, since the soil in Finland is poor in selenium, the authorities decided in the early 1980s to add selenate to commercial fertilizers. A survey of selenium status among 108 healthy young people showed an increase in the blood selenium level of about 50 percent after four years. [23]

A similar problem with the level of minerals in the soil exists for the content of magnesium. Often when the soil gets depleted of magnesium from heavy use, this essential mineral is not included in soil amendment with fertilizers. Produce grown in soil with an adequate level of magnesium will contain more magnesium than produce grown in soil deficient in magnesium.

Perhaps as many as 70-80% of the US population is magnesium-deficient, which causes many health problems. [24] Magnesium supplements (chloride, malate or citrate) can provide an adequate level when vegetables grown in soil with adequate magnesium are not available.

3. Stress and the modern lifestyle increase the need for nutrients

Mental stress increases the excretion and hence the need for many nutrients. Among the most important are magnesium and vitamin C, both of which are used by the body in larger quantities during periods of physical and mental stress. [24,25] Compared with our past as hunters and gatherers, today´s stress is often of a more permanent nature. Instead of experiencing occasional situations where we had to fight or flee, many of us live with recurring stress day in and out.

Vitamin C protects the brain and nervous system from damage caused by stress because the synthesis and maintenance of chemical neurotransmitters such as adrenaline and noradrenaline requires adequate levels of vitamin C. [25]

Vitamin C is also needed to repair collagen which is essential for skin, blood vessels, bones and joints, and muscles. When these are damaged by physical stress, extra vitamin C is necessary.

A controlled trial of 91 adults who experienced increased anxiety and stress 2-3 months after an earthquake in New Zealand in 2011 was divided into three groups, two were given a broad spectrum supplement of micronutrients in low or higher doses. [26] The supplements were found to alleviate the experience of stress, with the biggest dose having the biggest effect.

Our sedate, modern lifestyle reduces the need for energy from food, which implies a lower food intake or obesity. Loren Cordain, PhD, and coworkers have estimated that hunter-gatherers had significantly higher energy needs than the typical modern office worker. [27]

A lower energy intake generally reduces the absolute intake of all nutrients, while the need for some nutrients is not always reduced proportionally with energy intake. Overall this suggests that more exercise along with a more nutritious diet, including supplements of essential nutrients and less carbohydrates, will help to prevent obesity and maintain health.

Processing of food reduces its nutritional content, and the finished products are often based on fractions of the original foods. One example is milling grain to make white flour, [1] which has a lower nutritional density than whole grain flour.

The reduction in nutritional value has accelerated since whole foods are now divided into pieces, for example, boneless chicken breast. When meat is injected with saline to increase the volume, the relative level of essential nutrients is reduced. In the United States, many supermarkets in low-income rural and inner city areas have a limited selection of nutrient-dense foods, compared with high-income areas. [28]

4. Environmental pollutants increase the need for nutrients

The need for efficient detoxification and excretion is greatly increased by environmental pollution from the chemical industry, herbicides and pesticides used by industrial agriculture, antibiotic treatment of animals, transport, and plastic packaging. [29]

In our polluted world, the increased toxic load may be compensated for by an increase in nutrients to promote detoxification. One can respond by taking large doses of supplements of essential nutrients, for example, antioxidants vitamin C and E, and an adequate dose of selenium, which help the body detoxify harmful chemicals. Also helpful is regularly taking sauna baths, fasting periodically, and eating an excellent diet that includes generous portions of dark green leafy vegetables and colorful vegetables and fruits. [30]

A recent study predicts that global warming may reduce the nutrient density in many foods worldwide. [31] Atmospheric CO2 is estimated to surpass 550 ppm in the next 30-80 years, leading to larger crops with lower content of protein, iron and zinc per energy unit.

Assuming that diets remain constant, while excluding other climate impacts on food production, the researchers estimated that elevated CO2 could cause an additional 175 million people to be zinc deficient and an additional 122 million people to be protein deficient in 2050. Anemia would increase significantly if crops lose even a small amount of iron. The highest risk regions – South and Southeast Asia, Africa, and the Middle East – are especially vulnerable, since they do not have the means and access to compensate using nutritional supplements.

5. The RDA for essential nutrients is too low

The recommended nutrient reference intake (NRI) has been defined by UK authorities and the EU Food Safety Agency as the dose that is adequate for 95 percent of the population. [32] These authorities have given recommendations for a total of 41 chemical substances, [33] including 13 vitamins, 17 minerals/trace elements, 9 amino acids and two fatty acids. The problem with such guidelines is that when using the same 0.95 fraction for just 16 of the essential nutrients, the fraction of the overall population that has their needs met with the RDA is less than half (0.9516 = 0.44).

Given the above assumption, the proportion of the population having all nutrient needs met falls below 25 percent for 30 nutrients (0.9530 = 0.21). These 25 percent will not necessarily get optimal amounts, just enough so that they probably will have no deficiencies in accordance with established standards. Each individual is different and has different biochemical needs, so we all need different doses of essential nutrients. Many vitamins and minerals can give additional benefit when taken at higher doses.

The need for several essential nutrients increases with age and sickness. This applies, for example, to vitamin C, vitamin D, magnesium, and iron. In 2017 the Norwegian Food Safety Authority proposed to revise the official maximum levels for vitamins and minerals in dietary supplements. [34]

Their proposal introduced four different age categories with separate maximum intakes. Initially, the agencies proposed to revise the daily doses allowed in dietary supplements for folic acid, magnesium, calcium, vitamin C and D. At the same time, maximum rates were temporarily suspended for vitamins A, E, K, thiamine (B1), riboflavin (B2), niacin (B3), pantothenate (B5), pyridoxine (B6), cobalamine (B12), biotin, and for phosphorus, iron, copper, iodine, zinc, manganese, selenium, chromium, molybdenum, sodium, potassium, fluoride, chloride, boron and silicon.

The upper limits for some nutrients may be changed in the future. Unfortunately, Norwegian nutrition “experts” will likely continue to limit allowable doses below those freely available in the US and even Sweden.

6. An optimal nutrient intake promotes health and delays aging

A spokesperson for optimal nutritional intake is the well-known biochemist Bruce Ames, who proposed the “triage theory of nutrients,” in which enzymes responsible for cell maintenance functions evolved to have lower affinity for the essential vitamin and mineral cofactors than the enzymes responsible for short-term survival, to preserve life during times of famine. [35]

Thus, higher levels of vitamins and minerals may delay mitochondrial aging, speed up the repair of large molecules such as DNA and collagen, and generally improve other cellular functions. This is an important rationale for taking higher doses of vitamins and minerals than recommended reference intakes.

Dietary supplements can slow the aging process, in part by reducing the harmful effects of free radicals, known to be involved in many diseases such as cardiovascular disease and cancer. [36]

Naturally occurring hormones and/or supplements of cofactors needed for optimal hormone production in the body can have a significant life-prolonging effect if the body produces less than optimal amounts. [37] This is especially relevant for those with a genetic predisposition for disease.

An optimum intake of all nutrients is difficult to achieve even for those who eat almost exclusively an excellent diet of nutrient dense foods, such as meat and innards, fish, shellfish, fowl, eggs, nuts, mushrooms, and vegetables, berries and nutritious fruits. Some nutrients such as folic acid or carotenoids in vegetables are absorbed better from processed than unprocessed foods.

Although vegetables are often considered to be a good source of vitamins, for example vitamin A from carrots, vitamin A is only found in animal products such as liver, egg yolk, fish cod and cod liver oil. Although eating raw vegetables is helpful for several reasons (vitamin C, fiber, microbiota), carotenoids (alpha/beta-carotene, lutein, lycopene) in vegetables are less well absorbed from raw than cooked food and better absorbed in the presence of added fat. [38,39].

Nutrients in vegetables are better absorbed when finely chewed, graded, or mashed [38], and cooking and grinding meat reduces the energy required to digest it [40] and increases nutrient absorption [41].

Orthomolecular pioneer Abram Hoffer and Orthomolecular News Service Editor Andrew W. Saul suggested this list of daily intakes of vitamins and minerals. [42] The Norwegian 2017 recommendations for adult men and women [43] are given in comparison. Individual needs may vary substantially from person to person and also with health status.

The figures for optimal intake are obtained from the Independent Vitamin Safety Review Panel of physicians, researchers and academics, who concluded:

“People are deceived in believing that they can get all the nutrients they need from a ‘balanced diet’ consisting of processed foods. To achieve an adequate intake of vitamins and minerals, a diet of unprocessed whole foods, along with intelligent use of dietary supplements is more than just a good idea: it is vital.” [44: 55]

A well-known example is vitamin C, which can effectively fight viral infections, prevent or reverse disease caused by bacteria, and help the body detoxify organic and inorganic toxins. [45] Vitamin C also reduces the risk for cancer, strengthens connective tissues (collagen), and counteracts stress by increasing the adrenal´s production of cortisol. The dose required is set according to the body’s need.

Nobel Price Laureate Linus Pauling suggested that an optimal daily intake of vitamin C could vary from at least 250 mg up to 20 grams per day. [46] Because unabsorbed vitamin C attracts water into the gut, some people may experience loose stools, gas and/or diarrhea by ingesting only 1-2 grams at a time, while others with a higher level of stress may tolerate 5-6 grams or more. The dose that causes loose stools is called the “bowel tolerance” for vitamin C. [47] To avoid the laxative effect of high doses, it is best to take vitamin C throughout the day in smaller divided doses.

When the body is stressed by disease, the gut will naturally absorb more vitamin C because the body needs more. To find the optimal dose, the intake should be increased until bowel tolerance is reached. Some people can tolerate more than 100,000 mg/d of vitamin C in divided doses during serious illness without having loose stool.

Liposomal vitamin C bypasses the normal bowel tolerance because it is absorbed directly through cell membranes, so higher doses can be tolerated without diarrhea.

7. A human right to receive correct information

Access to correct information about food and essential nutrients, including knowledge about the importance of food for health is a fundamental human right. Such information should not only provide a summary of the nutrient content of food, but in our opinion should also explain how dietary supplements can counteract deficiencies and prevent and reverse disease caused by nutrient deficiencies.

We should be free to purchase quality-controlled supplements of essential nutrients and to use them to counteract aging and damage from stress as part of a long-term health plan. The right to reject recommendations by doctors for symptomatic treatment with synthetic, some times life-threatening, drugs to alleviate symptoms should be included. [48,49]

I have not found any formulation of such rights from the Norwegian authorities. The role of parents and their right to receive correct health information is addressed in a book by lawyer Anne Kjersti C. Befring, a fellow at the University of Oslo since 2014. [50]

Summary

The use of dietary supplements is widespread. High doses of vitamins are thought to be helpful because they help the body recover from damage and maintain itself long-term. Many vitamins are not harmful in doses even 10 to 100-fold higher than officially recommended.

Some governments warn about possible negative side effects, even including increased mortality from “excessive” intake of certain supplements. However, supplements of essential nutrients have been available for more than 80 years. They are known to be safe, and the observed side effects are generally mild with few exceptions.

It is possible to ingest too much of certain vitamins and minerals (vitamin A, calcium, iron, copper, selenium) which may exacerbate an existing imbalance or lack of another mineral (magnesium, zinc). It is also important to balance intake of fatty acids in the omega-6 and omega-3 series, as most people get too much omega-6 and not enough omega-3.

Small children can be overdosed with adult doses of for example vitamin A or iron, and pills may be dangerous for babies or young children because they can get stuck in the throat. Therefore, I recommend consulting a doctor or nutritionist educated in orthomolecular medicine. Most people are likely to benefit from taking a broad-spectrum multivitamin/mineral supplement as a basic insurance against deficiencies.

Compared to pharmaceutical drugs, supplements of most essential nutrients are quite harmless. However, some supplements may have poor quality, or contain toxic metals such as lead or cadmium. Therefore, it is the duty of our authorities to ensure that potentially hazardous products or supplements of poor quality are not sold, and that consumers are offered fair prices in a free market.

An example where the Norwegian authorities do not follow up such basic duties is that pharmacies demand more than 1,600 Norwegian Kroner (about $190) per kg of vitamin C in powder form, which would cost less than $20 with free competition and no restrictions in permitted doses or outlets.

Those who want to use natural healing methods, such as the use of food and supplements of essential nutrients to prevent or reverse illness, should consult therapists who are qualified to give advice on how natural therapies can help.

I recommend that anyone interested in supplements read the references for this article as well as the archives of the Journal of Orthomolecular Medicine http://orthomolecular.org/library/jom/ and the Orthomolecular Medicine News Service http://orthomolecular.org/resources/omns/index.shtml . Both are free access online.

(Dag Viljen Poleszynski, PhD, is the editor of Helsemagasinet [Health Magazine] https://vof.no/arkiv/ . He has translated and published a large number of OMNS releases in Norwegian.)

 

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29. Waldbott GL. Health effects of environmental pollutants. Second edition. St. Louis, MI: The C. V. Mosby Company, 1978. ISBN-13: 978-0801653308

30. Rogers, Sherry A. Detoxify or die. Sarasota, FL: Sand Key Company, Inc., 2002. https://www.amazon.co.uk/s/ref=nb_sb_noss_2?url=search-alias%3Daps&field-keywords=Detoxify+or+die

31. Smith MR, Myers SS. Impact of anthropogenic CO2 emissions on global human nutrition. Nature Climate Change 2018; 8: 834-9. https://www.nature.com/articles/s41558-018-0253-3

32. Dietary Reference Values. https://en.wikipedia.org/wiki/Dietary_Reference_Values (9.1.2018)

33. Essential Nutrients. http://www.nutrientsreview.com/glossary/essential-nutrients (9.1.2018)

34. [Norwegian Food Authority. Revision of national maximum limits for vitamins and minerals in nutritional supplements – separate maximum limits; published 11.9.2016, last changed 6.21.2017]. https://www.mattilsynet.no/mat_og_vann/spesialmat_og_kosttilskudd/kosttilskudd/

35. Ames BN. Prevention of mutation, cancer, and other age-associated diseases by optimizing micronutrient intake. Journal of Nucleic Acids 2010; 210: 1-11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945683/

36. Halliwell B, Gutteridge HMC. Free radicals in biology and medicine. 5th edition. Oxford, NY: Clarendon Press, 2015. ISBN-13: 978-0198717485

37. Hertoghe T. The hormone handbook. Copyright (c) 2006 Thierry Hertoghe. Surrey, UK: International Medical Publications, 2006.

38. Edwards AJ, Nguyen CH, You CS, et al. a- og ß-carotene from a commercial carrot puree are more bioavailable to humans than from boiled-mashed carrots, as determined using an extrinsic stable isotope reference method. Journal of Nutrition 2002; 132: 159-67. https://academic.oup.com/jn/article/132/2/159/4687130

39. Unlu NZ, Bohn T, Clinton SK et al. Carotenoid absorption from salad and salsa by humans is enhanced by the addition of avocado or avocado oil. The Journal of Nutrition 2005; 135: 431-6. https://www.ncbi.nlm.nih.gov/pubmed/15735074

40. Boback SM, Cox CL, Ott BD et al. Cooking and grinding reduces the cost of meat digestion. Comparative biochemistry and physiology. Part A, molecular & integrative physiology 2007; 148: 651-6. https://www.ncbi.nlm.nih.gov/pubmed/17827047

41. Carmody RN, Wrangham RW. Cooking and the human commitment to a high-quality diet. Cold Spring Harbor Symposium on Quantitative Biology 2009; 74: 427-34. https://www.ncbi.nlm.nih.gov/pubmed/19843593

42. Hoffer A, Saul AW. Orthomolecular medicine for everyone. Laguna Beach, CA: Basic Health Publications, Inc., 2008. ISBN-13: 978-1591202264

43. Hjartåker A, Pedersen JI, Müller H mfl. Grunnleggende ernæringslære. 3. utgave. [Basic nutrition] Oslo: Gyldendal Norsk Forlag AS, 2017.

44. Levy TE. Vitamin C, infectious diseases, & toxins. Curing the incurable. 3rd Edition. (c)Thomas E. Levy 2011. Medfox Pub. ISBN-13: 978-0977952021

45. Pauling L. How to live longer and feel better. New York: W. H. Freeman and Company, 1986. ISBN-13: 978-0870710964

46. Cathcart, RF III. The method of determining proper doses of vitamin C for the treatment of disease by titrating to bowel tolerance. Journal of Orthomolecular Medicine 1981; 10: 125-32. http://orthomolecular.org/library/jom/1981/pdf/1981-v10n02-p125.pdf

47. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients. A meta-analysis of prospective studies. JAMA 1998; 279: 1200-5. https://jamanetwork.com/journals/jama/fullarticle/187436

48. Moore TJ, Cohen MR, Furberg CD. Serious adverse drug events reported to the Food and Drug Administration, 1998-2005. Archives of Internal Medicine 2007; 167: 1752-9. https://www.ncbi.nlm.nih.gov/pubmed/17846394 .

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50. Befring AKC. Helse- og omsorgsrett. [Health and Care] Oslo: CappelenDamm AS, 2017.

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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