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.


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 ligase is a characteristic Nrf2 target gene, which establishes 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.


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 giant knotweed and 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.”


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+


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 100% more powerful as an antioxidant than the best single plant ingredient.


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+    3,376    5,569 2,758 221,866 34,169 267,738
Results are expressed in micro mole TE/g

The total Ultimate Protector+ ORAC5.0 value per serving of 6 small vegetarian capsules (containing 3.55 g) is over 950,00 Micro mole TE.

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).


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)


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)


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)


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.


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!







Fred Liers PhD restore liquid mineral supplement gut healthHeard of RESTORE liquid mineral supplement? If not, you’re about to discover something important for gut health.

RESTORE™ is formulated to help restore gut health. It works by strengthening the integrity of tight junctions in your intestinal wall.

Maintaining tight junctions is important because they protect your body from substances entering the blood stream. Restore also supports the communications systems of the bacteria in your microbiome.

Tight junctions are natural barriers protecting the lining of your gut barrier, organs such as kidneys and heart, and the blood-brain barrier thereby keeping out unwanted substances. Even as we take in nutrients from the GI tract, the function of tight junctions is maintaining the integrity of the gut wall and other barriers that protect the body.

These days, our gut membrane has a tough job keeping out unwanted substances. Because tight junctions are weakened by many things, including highly processed foods, especially those containing gluten and gliadin, the herbicide glyphosate (the primary ingredient in RoundUp weedkiller), and other exposures like electromagnetic fields (EMF) from digital devices and Wi-Fi networks.

As a result of weakened tight junctions, undesirable substances from food proteins, harmful chemicals and other toxins can slip though into our bloodstream. This can lead to a powerful immune response that can weaken immunity and cause significant inflammation. Foreign substances in the bloodstream can also result in extreme food allergies and food sensitivities to various toxins entering the body.

We live in an age in which our microbiome health is under assault. Studies show our ancient ancestors had 20,000–30,000 different strains of beneficial bacteria in their GI tracts. Many people today have just 5,000 or less. Why is that?

There are many reasons for low microbiome diversity. These reasons include antiobiotic use (both from pharmaceuticals and foods), glyphosate (which essentially acts like an antibiotic), processed foods (especially those containing gluten and gliadin), and systemic degradation of the gut environment rendering it less hospitable for maintaining health populations of gut flora.

These impacts are significant because diversity in your microbiome not only supports gut health, but also appropriate brain health, immune system health, and overall vitality. Restore acts as a “microbiome fertilizer” helping establish and maintain healthy microbiota.

In fact, Restore contains important “redox” molecules produced millions of years ago by existing soil bacteria. These molecules are an important part of communications systems within the body between gut bacteria and with the body’s mitochondria. These communication systems play an important role in establishing proper homeostasis throughout the body.


There are important reasons to try Restore—whether or not you experience significant gut health issues. These reasons include:

• Maintaining strong tight junctions for mega membrane health, and helping the body restore tight junction integrity

• Creating an environment in which beneficial bacteria can thrive

• Boosting microbiome diversity

• Healing the gut

• Mitigating the adverse effects substances like antibiotics, gluten/gliadin, glyphosate, and GMOs on microbiome health

• Supporting immune system function

• Protecting integrity of blood-brain barrier

Other benefits include support for respiratory wellness, enhancing mental clarity, and promoting proper homeostasis throughout the body.

For all these reasons and more, you should consider taking Restore. You can start by taking one teaspoon or less daily, and gradually increasing your dose to one tablespoon or more.Restore for gut health liquid supplement

I have taken Restore daily for more than two years, and benefit greatly from it. The most noticeable effects are a complete cessation of spring allergies (after two decades of worsening symptoms), greater clarity of thinking, and improved overall well being. I have seen other people get good results with a variety of conditions from dysbiosis to gluten/gliadin sensitivity.


You can learn more about Restore on our website. Also, the Restore website offers in-depth information and videos. Here is how the Restore website and Dr. Zach Bush describe the formula:

Restore is a dietary supplement supplying first line defense against daily exposure to environmental and food-borne factors. It helps create an optimal environment or ecology in the gut membrane for beneficial or “good” bacteria to flourish. Beneficial gut flora protect your immune system and maintain health. Restore is a scientifically proven soil-derived mineral supplement designed to support protection of the intestinal walls.

Restore protects the entire gastrointestinal (GI) tract against agricultural herbicides, antibiotics, GMOs, gluten, and food-borne toxins. It helps create an environment in which 20,000–30,000 different strains of beneficial gut bacteria can thrive. This is a far different mode of action from probiotics, most of which contain just 3–30 strains of beneficial bacteria.

Restore helps create a strong immune system along with proper gut function. Microbiome balance and tight junction integrity are known to constitute a significant part of the immune system. They directly affect DNA transcription of cells to promote optimal health and prevent a leaky gut syndrome, thereby improving gut intelligence.

Seventy percent (70%) of our immune system is found in our gut. We need tens of thousands different strains of good gut bacteria to support a healthy immune system. Clinical experience, in addition to cell culture studies, support the theory that Restore’s proprietary formula creates the optimal environment in the gut to create a tight junction barrier and maintain our health and wellness.

Restore is a daily liquid supplement designed to support the protection of the entire gastrointestinal (GI) tract against agricultural herbicides, antibiotics, GMOs, gluten and food-borne toxins by helping to create an environment where between 20,000-30,000 different strains of good gut bacteria thrive. Most probiotics on the market contain fewer than 24 different strains of good gut bacteria.


Restore is ideal for individuals suffering from gut health issues. Yet, it is also excellent for supporting and maintaining gut health generally. That is the reason we at HPDI consider Restore important enough to designate as a foundational supplement, one of the top six supplements you need for good health.

Given the safety and effectiveness of Restore, there is broad applicability for its use. This is especially true because gut and microbiome health are under constant assault. These assaults range from multiple environmental and lifestyle factors—including poor diets high in processed foods, antibiotics in pharmaceuticals and animal foods—to massive glyphosate (herbicide) contamination of foods, soils, air, and water.

Let Restore be your first line of defense against assaults on your gut health, tight junctions, microbiome diversity, and immune function. As it says on the bottle, “Complete well-being begins in the gut.”


Gut Health – Effects of Glyphosate and Antibiotics
by Hank Liers, PhD and Fred Liers, PhD

Restore – 32 oz

Restore – 8 oz

HPDI Gut Health Formulas

HPDI Foundational Supplements

Restore blog (Restore4Life)


The Truth About Essential Fatty Acids

Dr. Hank Liers, PhD essential fatty acidsMany in the field of nutrition have lost sight of the fact that there are two essential fatty acids needed by the body. Many people recommend omega-3 fatty acids assuming the the body gets sufficient omega-6 from the diet. The truth about essential fatty acids is more complicated. This article will show the more complete and correct picture.


Fatty acids are part of the lipids class, widely found in nature, food, and organisms. These fatty acids are a critical constituent of the cell membranes in all of the trillions of cells in the body. They have important biological functions including structural, communication, and metabolic roles, and they represent an important source of energy. Their metabolism produces a huge quantity of adenosine triphosphate (ATP). The beta-oxidation of the fatty acids is a well-known process, mostly used by the heart and the muscular tissue to obtain energy.

Figure 1 below shows a schematic diagram of what a fatty acid looks like. One end of the structure in all cases has a carboxylic acid group (COOH) and the other end in all cases has a methyl group (CH3). Saturated fats have single bonds (-) between all carbon atoms (C), but unsaturated fats have a number of double bonds (=) between some of the carbon atoms.

essential fatty acids

Figure 1 – Basic diagram of fatty acids structure

The human body can synthesize many of these fatty acids, except the essential fatty acids (PUFAs) linoleic acid (LA) and alpha-linolenic acid (ALA). These two are generally found in various vegetable oils, but their important metabolites are found mainly in special vegetable oils such as borage oil and in fish oils. Linoleic acid is the most abundant fatty acid in nature, and it is the precursor of other omega-6 fatty acids. Omega-3 fatty acids are synthesized from alpha-linolenic acid.

Once ingested, short-chain PUFAs are converted to long-chain fatty acids. These are critical for mammalian cells in order to perform various biological functions, such as sustaining the structural integrity of cellular membranes and serving as signaling molecules. They are highly enriched in brain tissues, where they participate in the development and maintenance of the central nervous system during both embryonic and adult stages.

Polyunsaturated fatty acids have been extensively researched. They include the essential fatty acids linoleic acid (an omega-6) and alpha linolenic acid (an omega-3). Omega-3s are not abundant in our food chain. There is none in corn oil and very little in soy oil, the two most widely used food oils. Therefore, nearly all the early research with polyunsaturated oils utilized omega-6 fatty acids, predominantly as linoleic acid.

Fish oils were neglected out of ignorance or because the investigators chose to pass over these cholesterol-containing oils. Concern eventually developed over the close association between increasing incidence of mammary tumors and high intake of omega-6 polyunsaturated fatty acids. After some years, researchers finally turned their investigations to the interrelationship between dietary omega-6 and omega-3 fatty acids.


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

essential fatty acids

Figure 2 – fatty acid metabolism pathways in the body

The diagram shows a series of enzyme induced reactions that either add a double bond or two additional carbon/hydrogen pairs to the fatty acid. The enzymes that make this happen are called desaturase and elongase. The desaturase enzymes are given a number for the carbon number (that the enzyme is working on) from the methyl end of the fat. These same enzymes work on all of the fatty acid types. For example, Delta 6 desaturase causes an additional double bond to be inserted into both alpha-linolenic (omega-3) and linoleic acid (omega-6) (as well as oleic acid and palmitoleic acids).

In this way, the body is able to produce a wide variety of fatty acids that have their own unique effects on biochemistry. Some of these are more important than others. In particular, the omega-3 essential fatty acid eicosapentanoic acid (EPA), the omega-6 essential fatty acid dihomo-gamma-linolenic acid (DGLA), and the omega-6 essential fatty acid arachidonic acid (AA) are precursors for a class of chemicals called eicosanoids/prostaglandins that have far reaching affects on key body functions.


Eicosanoids are prostaglandins that affect many aspects of health both positively and, in some cases, negatively. All known eicosanoids and prostaglandins are formed from the essential fatty acids linoleic acid (omega-6, or n-6), alpha linolenic acid (omega-3, or n-3), their “enhanced” derivatives, and from the omega-3 fatty acids in fish oils.

Prostaglandins are short-lived highly active, hormone-like chemicals that are found in every cell of the body. They are regulators of cell activity and essential for maintaining health. Each cell type or organ produces its own form of prostaglandin to carry out its functions. There are three types of prostaglandins: PG1, PG2, and PG3.

Series 1 Prostaglandins (PG1), derived from gamma-linolenic acid (GLA), the active component of borage oil, has many beneficial effects: It makes platelets less sticky, lowers blood pressure by relaxing smooth muscles in the walls of arteries, increases loss of sodium and water, decreases inflammation and enhances immunity.

Series 2 Prostaglandins (PG2), also derived from GLA, is used in “fight or flight” (stress) situations, – the fight against danger, or the flight from it. In modern lifestyles which are high in stress but low in physical activity, continuous production of Series Two Prostaglandins results in sticky platelets, high blood pressure, increased water and sodium retention, increased inflammation and decreased immune system capabilities.

Series 3 Prostaglandins (PG3), derived from eicosapentaenoic acid (EPA), the active component of fish oil, has beneficial effects. They block the detrimental effect of the Series 2 Prostaglandins, preventing them from being made in the body. As a result the platelets are less sticky, blood pressure is lower because the muscles in the walls of our arteries remain relaxed, loss of sodium and water by the kidneys takes place more effectively, inflammation response is decreased, and immune function is efficient.

It is now known that the ratios of these dietary fatty acids are very important. Consumption of linoleic acid leads to production of the enhanced fatty acid, arachidonic acid (20:4n-6). Prostaglandins based on arachidonic acid exacerbate stress and inflammatory states, and suppress immunoprotective functions (i.e. resistance to disease). Too much linolenic acid and other omega-3s may cause excessive bleeding during injury, surgery, or childbirth. Large amounts of any of these unsaturated fatty acids in the diet without a compensatory increase in antioxidant nutrients (especially Vitamin E), can speed oxidative damage to tissues, resulting in accelerated aging while increasing the risk of degenerative diseases.

Yet, a balanced ratio of both omega-3 and omega-6 fatty acids in the diet offers very positive health benefits. When omega-3 fatty acids predominate, the body will produce less arachidonic acid (20:4n-6). Immunity improves and inflammation subsides.

Essential Fats

Unfortunately, our Western diet has been almost devoid of omega-3 fatty acids. Creating the optimum intake of omega 3-to-omega 6 unsaturated fatty acids has become, therefore, an issue of prime importance for anyone concerned with health. We need to evaluate carefully the amounts of linoleic acid (n-6) we consume relative to our intake of alpha-linolenic acid (18:3n-3) and fish oils (EPA:20:5n-3 and DHA:22:6n-3).


The diagram in Figure 3 shows details of the omega-6 and omega-3 pathways. Pathway specifics indicate key eicosanoids (series 1 prostaglandins, series 2 prostaglandins, and series 3 prostaglandins), oil sources, and important nutrient cofactors that are needed for the reactions to take place.

essential fatty acids

Figure 3 – Essential Fatty Acids – pathways in the body

The information is this diagram gives the clues we need in order to provide optimal types and amounts of omega-6 and omega-3. For example, I have chosen for my essential fatty acid product cold pressed borage oil as the best natural source of gamma linoleic acid (GLA). It contains 20% by weight — the highest amount found in natural oils.


Work by Chapkin et. al. (see references 1–4 below) has identified the potent synergistic relationship between GLA, an omega-6 fatty acid, and the well-known omega-3 fatty acids. Chapkin has shown that, rather than simply the quantity of dietary omega-3s, it is the ratio of omega-6 to omega-3 fatty acids that is important in achieving full cardiovascular health and inflammatory control.

Furthermore, Chapkin has identified the ideal ratio. His published work deals with the importance of mixed diets supplying both linoleic and linolenic acids. To underscore the importance of these two fatty acids, refined oil supplements rich in enhanced forms were used. “Enhanced forms” are fatty acids derived from the original. They are one or more steps closer to the actual eicosanoid. In the human body, alpha linolenic acid (18:3n-3) is eventually converted to eicosapentaenoic acid (EPA, 20:5n-3) and linoleic acid (18:2n-6) is converted to gamma-linolenic (GLA, 18:3n-6) as its first enhanced form. Both enhanced fatty acids are precursors to eicosanoids.

In Chapkin’s research, superior health benefits were delivered by the mixed diet that supplied the eicosanoid precursors in a specific ratio. The balanced ratio of enhanced Omega-6 (GLA)-to-Omega-3 (EPA) fatty acids was 1:4.


Based upon the science discussed above, I developed a product with the correct Omega-6 (GLA)-to-Omega-3 (EPA) ratio and with proper amounts. It is available to you as Hank & Brians Essential Fats Plus E from Health Products Distributors, Inc. (HPDI).

Essential Fats Plus E


  1. UNIQUE COMBINATION — Essential Fats (EPA, DHA, GLA) plus Vitamin E. This unique formula offers more than one type of Vitamin E (not just d-alpha-tocopherol) and balanced essential fats.
  2. BALANCED ESSENTIAL FATS— Many EFA supplements contain only omega-3s, but for optimal function the body requires a balance of omega-3 and omega-6 essential fats. In addition, our special formula provides a 4-to-1 ratio of EPA to GLA in order to achieve a balance you need for optimal health.
  3. FULL-SPECTRUM VITAMIN E — Tocotrienols and tocopherols in this formula are natural vitamin E substances derived from oryza rice bran oil and protect polyunsatured EFAs against free-radical damage both in the capsule and in your body. Many Vitamin E supplements contain only d-alpha tocopherol, which is only a single component of the full-spectrum Vitamin E in this formula.
  4. ULTRAPURE — Molecularly distilled oils of extremely high-purity containing no PCBs, heavy metals, or oxidized contaminants. Free of excipients, additives, and common food allergens!

COMPOSITION: Six softgel capsules provides the following percentages of the Daily Value.

EPA (Eicosapentaenoic Acid 20:5 omega 3)
(from 2,000 mg of purified fish oils)
360 mg *
DHA (docosahexaenoic Acid 22:6 omega 3)
(from 2,000 mg of purified fish oils)
240 mg *
GLA (Gamma Linolenic Acid 18:3 omega 6)
(from 450 mg of cold pressed borage seed oil)
90 mg *
Vitamin E (d-alpha-tocopherol) (from 180 mg of Oryza rice bran oil) 24 IU 81%
Mixed Tocotrienols (d-gamma, d-alpha, and d-delta)
(from 180 mg of Oryza rice bran oil)
28.8 mg *

* No established Daily Value
† Daily Values based on a 2,000 calorie diet


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

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


Please note that genetic testing for a wide range of genes and the enzymes they produce has indicated that essential fatty acids can be an important factor in helping the body overcome a variety negative gene variations. These negative gene variations include genes that relate to: 1) Inflammatory Response, 2) Exercise Performance, 3) Exercise Recovery, 4) Cardiovascular Fitness, 5) Body Composition, and 6) VO2 Max, Aerobic Capacity.

We will discuss this more deeply in a future blog article.


The body is best protected from a range of health issues when we supply a mixed diet of both omega-3 and omega-6 essential fatty acids. Studies show that we do not need to consume large amounts of fatty acids if the ratio is correct. These findings indicate that, for a typical human body, amounts of 90 mg GLA (18:3n-6) to 360 mg EPA (20:5n-3) taken daily will provide for the optimum production of the three major prostaglandins. These amounts are found in Hank & Brians Essential Fats Plus E.


The following includes abstracts of Chapkin’s published research on essential fatty acids.


Chapkin RS Somers SD Erickson KL

Dietary manipulation of macrophage phospholipid classes: selective increase of dihomogammalinolenic acid.

In: Lipids (1988 Aug) 23(8):766-70

Because alterations in the dietary content of fatty acids are an important method for modulating macrophage eicosanoid production, we have quantitated the levels of n-6 and n-3 polyunsaturated fatty acids in peritoneal macrophage individual phospholipids from mice fed diets (3 wk) with either safflower oil (SAF), predominantly containing 18:2n-6, borage, (BOR) containing 18:2n-6 and 18:3n-6, fish (MFO) containing 20:5n-3 and 22:6n-3, and borage/fish mixture (MIX) containing 18:2n-6, 18:3n-6, 20:5n-3 and 22:6n-3. Dietary n-3 fatty acids were readily incorporated into macrophage phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI). The increase in n-3 fatty acid levels was accompanied by a decrease in the absolute levels of 18:2n-6, 20:4n-6 and 22:4n-6 in PC, PE and PS. Interestingly, PI 20:4n-6 levels were not significantly lowered (P greater than 0.05) in MIX and MFO macrophages relative to SAF and BOR. These data demonstrate the unique ability of this phospholipid to selectively maintain its 20:4n-6 levels. In BOR and MIX animals, 20:3n-6 levels were significantly increased (P less than 0.05) in all phospholipids relative to SAF and MFO. The combination of borage and fish oils (MIX diet) produced the highest 20:3n-6/20:4n-6 ratio in all phospholipids. These data show that the macrophage eicosanoid precursor levels of 20:3n-6, 20:4n-6 and n-3 acids can be selectively manipulated through the use of specific dietary regimens. This is noteworthy because an increase in phospholipid levels of 20:3n-6 and 20:5n-3, while concomitantly reducing 20:4n-6, may have therapeutic potential in treating inflammatory disorders.

Institutional address: Department of Human Anatomy School of Medicine University of California Davis 95616.



Chapkin RS Carmichael SL

Effects of dietary n-3 and n-6 polyunsaturated fatty acids on macrophage phospholipid classes and subclasses.

In: Lipids (1990 Dec) 25(12):827-34

This study examined the effects of n-3 and n-6 polyunsaturated fatty acid alimentation on murine peritoneal macrophage phospholipids. Mice were fed complete diets supplemented with either corn oil predominantly containing 18:2n-6, borage oil containing 18:2n-6 and 18:3n-6, fish/corn oil mixture containing 18:2n-6, 20:5n-3 and 22:6n-3, or fish/borage oil mixture containing 18:2n-6, 18:3n-6, 20:5n-3 and 22:6n-3. After two weeks, the fatty acid levels of glycerophosphoserines (GPS), glycerophosphoinositols (GPI), sphingomyelin (SPH), and of the glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) phospholipid subclasses were determined. We found that mouse peritoneal macrophage GPC contain primarily 1-O-alkyl-2-acyl (range for the dietary groups, 24.6-30.5 mol %) and 1,2-diacyl (63.2-67.2 mol %), and that GPE contains 1-O- alk-1′-enyl-2-acyl (40.9-47.4 mol %) and 1,2-diacyl (44.2-51.2 mol %) subclasses. In general, fish oil feeding increased macrophage 20:5n-3, 22:5n-3 and 22:6n-3 levels while simultaneously reducing 20:4n-6 in GPS, GPI, GPE and GPC subclasses except for 1-O-alk-1′-enyl-2-acyl GPC. Administration of 18:3n-6 rich diets (borage and fish/borage mixture) resulted in the accumulation of 20:3n-6 (2-carbon elongation product of 18:3n-6) in most phospholipids. In general, the novel combination of dietary 18:3n-6 and n-3 PUFA produced the highest 20:3n-6/20:4n-6 phospholipid fatty acid ratios. This study demonstrates that marked differences in the responses of macrophage phospholipid classes and subclasses exist following dietary manipulation.



Fan YY Chapkin RS

Mouse peritoneal macrophage prostaglandin E1 synthesis is altered by dietary gamma-linolenic acid.

In: J Nutr (1992 Aug) 122(8):1600-6

The ability of dietary gamma-linolenic acid [18:3(n-6)] to modulate prostaglandin biosynthesis in mouse resident peritoneal macrophages was determined. Mice were fed diets containing corn oil, borage oil or evening primrose oil or a mixture of borage and fish oils. After 2 wk, resident peritoneal macrophages were isolated and stimulated with unopsonized zymosan to induce prostaglandin synthesis. Borage oil, primrose oil and fish-borage oil mixture dietary groups (containing 25.6, 11.9 and 19.5 g gamma-linolenic acid/100 g fatty acids, respectively) had significantly (P less than 0.05) enhanced prostaglandin E1 synthesis (39.7, 29.4 and 73.0 nmol prostaglandin E1/mg protein, respectively) compared with corn oil-fed (containing less than 0.1 g gamma-linolenic acid/100 g fatty acids) animals, which synthesized less than 0.1 nmol prostaglandin E1/mg protein. Borage oil- and fish-borage oil mixture-fed mice had the highest biosynthetic ratio of prostaglandin E1/prostaglandin E2 (E1/E2 approximately 0.2). Macrophages from borage oil-fed mice synthesized the lowest amount of prostacyclin (198.7 nmol 6-keto-prostaglandin F1 alpha/mg protein) compared with corn oil-, primrose oil- and fish- borage oil mixture-fed mice (379.7, 764.8 and 384.2 nmol 6-keto- prostaglandin F1 alpha/mg protein, respectively). In addition, borage oil-, primrose oil- and fish-borage oil mixture-fed mice had significantly (P less than 0.05) higher levels of dihomo-gamma- linolenic acid [20:3(n-6)] in membrane phospholipids (5.5, 3.5 and 5.7 mol/100 mol, respectively) relative to corn oil-fed mice (2.0 mol/100 mol).



Fan YY Chapkin RS Ramos KS

Dietary lipid source alters murine macrophage/vascular smooth muscle cell interactions in vitro.

In: J Nutr (1996 Sep) 126(9):2083-8

This study was conducted to compare the impact of dietary lipids on the ability of macrophages to modulate vascular smooth muscle cell (SMC) DNA synthesis in vitro. C57BL/6 female mice were fed six different diets (6 mice/diet) containing 10% fat from corn oil (CO), borage oil (BO), primrose oil (PO), fish-corn oil mix (FC, 9:1, w/w), fish-borage oil mix (FB, 1:3, w/w), or fish-primrose oil mix (FP, 1:3, w/w) for 2 wk. Peritoneal macrophages were isolated from these mice, stimulated with zymosan or vehicle, and subsequently co-cultured with naive mouse aortic SMC in the presence of 3H-thymidine to measure SMC DNA synthesis. In this co-culture system, macrophages were seeded on 25-mm culture inserts (upper chamber) and SMC were seeded on 35-mm culture dishes (lower chamber). The two cell types were separated by a semipermeable membrane with a 30-kD cut-off. When quiescent SMC were co-cultured with macrophages, only the PO and FP diet groups had significantly (P < 0.05) lower SMC DNA synthesis compared with the control CO group whose diet contained no gamma- linolenic acid (GLA) or (n-3) polyunsaturated fatty acids (PUFA). In contrast, when cycling SMC were co-cultured with diet-modulated macrophages, all dietary groups except for those fed FC had significantly lower (P < 0.05) SMC DNA synthesis relative to the CO group. Although the level of GLA in PO and BO diets was different (11.5 and 22.3 g/100 g fatty acids, respectively), these treatments exerted comparable inhibitory effects on SMC DNA synthesis. The FP treatment consistently exhibited the lowest SMC DNA synthetic profile among the six dietary groups irrespective of SMC growth conditions. These data suggest that BO and PO alone or in combination with fish oil influence macrophage/smooth muscle cell interactions in a manner consistent with favorable modulation of the atherogenic process.

These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.


  1. Enig, Mary G. Know Your Fats: The Complete Primer for Understanding the Nutrition of Fats, Oils, and Cholesterol. Bethesda Press, 2000.


Dr. Hank Liers, PhD homocysteine coenzyme B vitaminsWe previously published an article titled FOLATE INGREDIENTS – FOLINIC ACID & 5-MTHF in which we discuss how coenzyme folate vitamins are far superior to the synthetic folic acid form. In today’s article, I take a more in-depth look at how homocysteine is formed from methionine, how genetics affects the metabolic pathways, and how B vitamins are used in metabolic pathways.

One way to look at the metabolic pathways of methionine (an essential amino acid) is that it provides a way for the body to convert this sulfur containing amino acid either to cysteine and its key by-products glutathione, taurine, and sulfates or allows remethylation back to methionine to occur using either the Folate Cycle or the Trimethyl glycine (betaine) pathways.

Figure 1 shows these metabolic pathways including the vitamins required at each step including vitamin B6 (as P-5-P), methylcobalamin, and 5-methyltetrahydrofolate (5-MTHF). In addition, it shows the key enzymes produced by the body at each step. These enzymes include CBS (cystathione beta synthase), BHMT (betaine homocysteine methyltransferase), MS (methionine synthase), and MTHFR (methylene tetrahydrofolate reductase).

homocysteine metabolism diagram

Figure 1. Metabolic Pathways in Methionine and Homocysteine Metabolism


It is highly important that the various metabolic pathways function correctly to keep homocysteine at healthy levels (6–8 µmol/L). Unfortunately, high levels of homocysteine in the body (10–20 µmol/L) are a factor in a wide range of health issues, including:

  • Greater risk for heart problems, including coronary artery disease, heart attacks, stroke, high blood pressure, congestive heart failure, and abnormal cholesterol levels. This is due to increased inflammation, sometimes due to blood clotting spontaneously, and because of blockages of the major arteries.
  • Mental abnormalities such as depression, anxiety, bipolar disorder, and other mental problems are more common among people with high homocysteine
  • Migraines and headaches in a significant percentage of the population
  • In those who suffer from high homocysteine due to having nutritional deficiencies anemia, aches and pains, hearing loss, age-related macular degeneration (ARMD), slowed development, and birth defects might also be possible
  • Greater risk for dementia, Alzheimer’s disease, brain atrophy, and other cognitive problems
  • In children, skeletal and developmental abnormalities including having a curved spine or protruding chest and rib cage. Some patients appear very tall and thin, and some might also have very long, thin “spider-like” toes and fingers.
  • Behavioral problems, including ADHD, autism and other learning disabilities


Ten or more years ago, questions of how genetics enters into homocysteine metabolism were unlikely to be asked. However, in recent years DNA testing has advanced and is now available to everyone (for example, see my article about Bodysync’s genetic test, DISCOVERING NUTRITIONAL NEEDS THROUGH ADVANCED GENETIC TESTING.

You may have heard a great deal about MTHFR (methylene tetrahydrofolate reductase). This gene is involved in folate metabolism and has a central role in methylation processes like repair of and building new DNA in dividing cells.

In the remethylation pathway for conversion of homocysteine to methionine, MTHFR plays a key role in converting folate into 5-MTHF which is needed along with B12 as methylcobalamin in order for the conversion to take place. Genetic variations in MTHFR have been studied in depth. Of the many variations studies the most significant ones appear to be variations of C677C such as C677T (referred to as heterozygous) or T677T (referred to as homozygous). The heterozygous variant appears in about 30–50% of the population and causes somewhat less efficiency in the conversion of folic acid to 5-MTHF. However, the homozygous variation occurs in about 10% of the population and can have serious effects due to converting little homocysteine back to methionine.

Another variation in MTHFR is called A1298A. These variations are A1298C and C1298C and will have similar effects to the C677C variations. It was interesting to me when I recently analyzed my Bodysync genetic test results showing I carry the variation A1298C (heterozygous), which indicates I may not be effectively converting homocysteine back to methionine.

Additionally, my Bodysync genetic test results also indicate that I have heterozygous variations in the CBS enzyme shown in Figure 1, as well as heterozygous variations in MTR and MTRR enzymes, which are involved with B12 levels in the remethylation pathway. These results indicate that I need to take higher levels of methylcobalamin and 5-MTHF.


Many of the B vitamins on the market today unfortunately are in synthetic form. The body can only use the natural coenzyme forms effectively. For example, the body needs vitamin B6 in the form of P-5-P (pyridoxal-5-phosphate), folate in the form of L-5-MTHF, and B12 in the form of methylcobalamin for proper metabolism of methionine. In some cases the body can use the synthetic forms of pyridoxine HCl, folic acid, and cyanocobalamin but pays a cost (e.g., in time and energy) by having to convert synthetic forms to coenzyme forms.

Add to the prevalence of synthetic B vitamins, the fact that genetic deficiencies are more common than previously assumed, and it becomes clear that the coenzyme forms of B vitamins in the proper amounts are extremely important.

Fortunately, I have always believed it best to include as many coenzyme forms as possible in the nutritional supplements I formulate (over the past 27 years). For example, all HPDI multivitamins include coenzymes of B1, B2, B6, B12, and folate (as 5-MTHF and folinic acid). This is uncommon in most multivitamin formulas on the market. For this reason our supplements are ideally suited to the prevention or resolution of most genetic problems regarding homocysteine.

In addition, I have always chosen to include higher amounts than most multivitamins on the market. We also make available 5-MTHF one milligram (1 mg) capsules and methylcobalamin five milligram (5 mg) sublingual tablets. When genetic variations are in play as discussed above, then providing relatively higher amounts of coenzyme B vitamins that support important requirements in the body seems necessary.

Interestingly, several other nutrients are involved in the pathways involving methionine and homocysteine. These include zinc, magnesium, and Vitamin B2. Our multivitamin formulas and magnesium formulas, especially Myo-Mag with its coenzyme B1, B2, and B6, are recommended to support these nutrient needs. Finally, it has been found that N-Acetyl-L-Cysteine (NAC) can significantly lower homocysteine (by up to 50%), most likely because its gives the body an excellent source of cysteine without have to use methionine.


In this article, I have shown the value of the use of genetic testing and high-quality coenzyme B vitamins in resolving health issues associated with high values of homocysteine in the body.





The Homocysteine Revolution by Kilmer S. McCully, MD

Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease
(Cell Death and Differentiation 11, S56–S64)


(coenzyme folate)

(vitamin B12)


HPDI Multivitamins