HOMOCYSTEINE GENETICS – COENZYME B VITAMINS

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

HEALTH ISSUES ASSOCIATED WITH HIGH HOMOCYSTEINE LEVELS

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

ROLE OF GENETICS IN HOMOCYSTEINE METABOLISM

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.

IMPORTANCE OF COENZYME FORMS AND PROPER AMOUNTS OF B VITAMINS

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.

SUMMARY

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.

 

SOURCES & RESOURCES

DISCOVERING NUTRITIONAL NEEDS THROUGH ADVANCED GENETIC TESTING.

FOLATE INGREDIENTS – FOLINIC ACID & 5-MTHF

The Homocysteine Revolution by Kilmer S. McCully, MD

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

PRODUCTS

5-MTHF
(coenzyme folate)

Methylcobalamin
(vitamin B12)

B-Complex-50

HPDI Multivitamins

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KIDS VITAMINS – NO KIDDING!

Fred Liers PhD kids mighty multi multivitamin chewableLooking for a high-quality, natural KIDS MULTIVITAMIN? Me, too. Do you look in vitamin stores, natural foods stores, and online marketplaces—in vain? I have.

A couple years ago, HPDI’s formulator, my father Hank Liers, PhD decided to reformulate our already excellent kids multivitamin—the Kids Mighty-Multi!—to make it better. His intentions were good: the world’s best designer of adult multivitamins would improve the best children’s vitamin.

My quandary? While Dr. Hank was busy at work reformulating our kids multi, the existing—and uber-excellent—original Kids Mighty-Multi! went out-of-stock, and never came back. Suddenly, my seven-year-old son’s “go-to” multivitamin was gone…indefinitely!

I took action—kids vitamins became my obsession—because I wanted the best multivitamin for my child. I searched everywhere for high-quality kids vitamins. Leaving no stone unturned, we tried them all—including organic, whole food, gluten-free, vegan-friendly brands with glossy labels. Did we find good ones? Not really.

What DID we find? Well, not much—and a lot. That is, not much in the way of high potency, high-purity, or advanced forms, like coenzyme vitamins. And a lot of false promises and junk ingredients. Like sugar and corn syrup and GMO ingredients—even from “reputable” brands.

Not to mention artificial sweeteners, colorings, flavorings, as well as toxic preservatives and fillers, which are the de facto standard in conventional products. Natural products are better—not always by as much as you’d expect.

chewable kids mighty-Multi! multivitamin

Looking for a good children’s multivitamin? Look no further than chewable Kids Mighty-Multi!

MY MULTIVITAMIN WISHLIST

Now in label-induced miasmic SHOCK…I proposed a reversal of terms. I simply wanted a lot of good things—like complete, balanced nutrients—and not much in the way of toxic additives.

Reeling, I scrawled a brief manifesto or “wishlist” for my ideal kids multivitamin:

“Great taste, high-purity, balanced nutrients at optimal levels, chewable; sugar free, non-GMO. No artificial ingredients, especially toxic sweeteners like aspartame or sucralose. No harmful additives or preservatives like sodium benzoate, BHT, or propylene glycol (no antifreeze please!); a few good-for-you functional ingredients.”

Was I asking *too* much? No way. Yet, I was giving up on finding a suitable kids multivitamin. My son instead began taking an HPDI adult multivitamin (Multi Two Caps) we scaled to his sixty five-pound weight. The taste wasn’t great—so we opened capsules directly into his juices and smoothies—because he’s not ready to swallow capsules or tablets whole. At best…a partial solution.

KIDS MIGHTY-MULTI! BACK — BETTER THAN EVER!

Then. It. Happened. Lighting struck—HPDI’s Kids Mighty-Multi! is BACK! Turns out my dad finished reformulating the world’s best kids multivitamin. He broke the news with a smile. Stunned and unbelieving…I took a breath. My heart skipped a beat. Then I grabbed a bottle!

Who knew it would take two years?—and now, who cares!? This month, HPDI proudly introduces a *new* Kids Mighty Multi!. Worth the wait? Yes. Because the new version is better than ever.

I’ve thrown away my wishlist. My search is over. Yours may be, too. Because no kids multivitamin comes *close* to Kids Mighty-Multi!. See the comparison chart and nutrient table (below).

A SERIOUS VITAMIN FOR KIDS – FINALLY!

What makes the new Kids Mighty-Multi! so good, and so much better? Let me count the ways. Here is a summary of benefits before I dive into discussing them in greater detail.

• Kids and adults love the taste!

• Full-spectrum of balanced, essential nutrients needed for creating, supporting, and maintaining excellent health for your child. Includes natural coenzyme form vitamins and Krebs’ cycle bionutrients that work with young bodies to provide energy for metabolic processes, healing, and optimal health.

• Bioavailable vitamin and mineral carriers the body recognizes and can assimilate rapidly. Plus, multiple carriers of individual nutrients ensure assimilation. Chewable form speeds uptake in the body.

Variety of well-known herbal ingredients, including quercetin, grape extract, turmeric, broccoli powder, and octacosanol

Complete, balanced supply of carotenoids, including beta-carotene, lycopene, and lutein

Functional ingredients built into every aspect of the formula, including the taste-enhancing package, herbal ingredients, and cofactors. Functional ingredients serve multiple purposes in supporting health.

• Flavored using only healthy, natural sweeteners and taste enhancers, including mannitol, fructooligosaccharides (FOS) (from chicory root), organic beet root powder, natural fruit flavor, xylitol, and stevia leaf extract. Taste enhancers exhibiting additional positive benefits (i.e., prebiotic effects, cavity prevention, and antioxidant action).

• NO refined sugars, no corn syrup, and…NO GMOs!

• NO artificial colorings or flavorings, artificial sweeteners (like aspartame, saccharin, or sucralose), or hydrogenated vegetable oils

• Excludes common food source allergens like wheat, corn, soy, and dairy

• Excludes unnecessary excipients, including fillers, binders, and additives

• Foundational formula ideal for providing basic nutrients for health. A high-quality multivitamin is the first step toward a complete nutritional supplement regimen. Formulated to work well with other HPDI foundational formulas, such as vitamin C / antioxidant formulas (like PRO-C™) and essential fatty acids (like Essential Fats plus E).

Kids Multivitamin comparison chart

TASTE-ENHANCING COMPLEX: FUNCTIONAL INGREDIENTS

Kids Mighty-Multi! tastes GREAT! Kids and adults LOVE the taste. From the perspective of your child’s taste buds, that’s *all* that matters.

But I want to talk a bit about the importance of healthy sweeteners…and how the best sweeteners perform double duty as health promoters.

WHY does Kids Mighty-Multi! taste so good? (Did I mention it contains NO refined sugars—or any artificial sweeteners or flavorings?)

Because Dr. Liers created a natural taste-enhancing complex. This taste-enhancing package includes xylitol, mannitol, FOS (fructooligosaccharides), beet root juice powder, natural fruit flavors, and stevia leaf extract.

Dr. Hank selected healthy, functional ingredients—as much as possible—in order to enhance the taste. That means these taste enhancers are not only NOT unhealthy like the refined sugars, corn syrups, and artificial sweeteners I found in so many other kids vitamins. But they are GOOD for you!

Functional sweeteners and taste-enhancing ingredients in Kids Mighty-Multi! include:

Xylitol – Proven sweetener that is a polyol (sugar alcohol) known to fight cavities, improve bone health, and more! (see: http://xylitol.org/about-xylitol/)

Mannitol – Natural polyol sweetener with added benefits as an antioxidant. Mannitol surprisingly has a very powerful effect on the hydroxyl free-radical. (see: https://www.ncbi.nlm.nih.gov/pubmed/9090754). Mannitol serves double duty as a healthy sweetener and important hydroxyl radical free-radical trapper.

• Fructooligosaccharides (FOS) (from chicory root) – Naturally sweet with no or low glycemic index. It is also a prebiotic that supports the growth of beneficial bacteria.

• Beet Root Powder (organic) – Naturally sweetens and colors Kids Mighty-Multi!. Beet is a functional ingredient providing methyl donors and easily assimilable iron. Moreover, Dr. Benjamin S. Frank found beets contain an amino acid the body uses to create its own dietary nucleic acids and a nutrient important to brain function (No-Aging Diet, 81).

• Berry & Fruit Extracts / Flavors – Mixed berry, strawberry, raspberry, and pomegranate. These berry extracts provide extremely good, fruity taste—bursting with berry flavors!

• Stevia Extract – Natural sweetens with little or no glycemic value. Kids Mighty-Multi! contains a newer, improved stevia extract which is de-bittered

• Malic Acid – Provides a naturally tart taste, supports the utilization of magnesium, and feeds into the Krebs’ cycle that makes cellular energy (ATP)

Why is choosing “good-for-you” functional sweeteners and taste enhancers important?

Because despite what adults might wish, sweeteners still comprise the largest percentage of kids multivitamins by weight. That means your child will be ingesting significant amounts (of whatever these sweeteners are) relative to the size of their multivitamin.

Who wants the bulk of their child’s multivitamin intake comprised of sugars, corn syrup, sucralose, or worse (think aspartame)? This is the reason natural sweeteners providing functional benefits make all the difference for health.

COMPLETENESS MATTERS – A LOT!

Kids Mighty-Multi! is nothing if not complete. As formulated by Dr. Hank Liers, it provides therapeutic levels of all essential vitamins, minerals, cofactors, and much more.

If you read labels (like I do), you’ll see most kids vitamins are “hit-or-miss.” They provide certain nutrients, but often completely miss others—usually with no rhyme or reason. (What was its formulator thinking?)

Missing important nutrients is bad for consumers—like you and your child—because all nutrients require other nutrients to “do a body good.” It’s called synergy, and it’s the way our cells are designed to work.

That means if you obtain sufficient amounts of a specific nutrient, but not enough of another, you may be unable to effectively utilize the nutrient you have—because utilization requires the nutrient you *don’t* have. Catch-22, huh? I’ll talk more about this later.

Do your child—and yourself—a favor: choose a complete multivitamin like Kids Mighty-Multi!.

kids mighty multi multivitamin

Kids Mighty-Multi! is nothing if not COMPLETE. (Tablets in photo appear larger than actual size.)

ADVANCED FORMS OF NUTRIENTS…LIKE YOU’VE NEVER SEEN

Then, there are advanced forms of nutrients, like coenzyme B vitamins. Most kids vitamins (and adult multivitamins) offer you the B complex vitamins as synthetic forms. How can you tell? Well, coenzyme vitamin B1 in Kids Mighty-Multi! is from Thiamin Diphosphate and is very different from synthetic “thiamine HCl.” Vitamin B2 is from Riboflavin-5′-Phosphate is not synthetic “riboflavin.” The vitamin B6 is from Pyridoxal-5′-Phosphate is not “pyridoxine HCl.” And so on.

What about vitamin B12 as toxic “cyanocobalamin”? Never. Kids Mighty-Multi! provides coenzyme B12 as methylcobalamin. Other brands sometimes use this form, but then provide synthetic forms for other B vitamins. That makes sense—NOT.

Sure, coenzyme B vitamins cost more to source. But the truth is, your body requires far less coenzyme form vitamins because they are the natural forms found in foods—you easily assimilate and utilize them. Kids Mighty-Multi! doesn’t need large amounts of coenzyme vitamins to give you big benefits.

Meanwhile, synthetic forms are not as easily assimilated—most go through a complex enzymatic breakdown before the body can use them. In some cases (for example if your child lacks certain enzymes due to genetics), syntethic forms cannot be broken down—or used—at all!

Case in point: Folate. Most kids vitamins give you “folic acid,” which is synthetic vitamin B1. A large percentage of the population (including me) lacks the gene providing the enzyme required to process folic acid. If folic acid builds up in cells (because it can’t be broken down), then it can be toxic. Solution: we use coenzyme folate—or 5-MTHF (5-methyl tetrahydrofolate) in Kids Mighty-Multi!. Problem solved.

Recall I said Kids Mighty-Multi! is complete?—and the importance of completeness in a multivitamin? Well, for example, if your kids’ multivitamin only provides synthetic vitamin B6 (as Pyridoxine HCl), it won’t be convertable into its biologically active (coenzyme) form without coenzyme vitamin B1 (Riboflavin-5′-Phosphate).

Did you catch that? To convert Pyridoxine HCl (synthetic vitamin B6) to its usable coenzyme form Pyridoxal-5′-Phosphate, you need coenzyme Riboflavin (Riboflavin-5′-Phosphate). You need a coenzyme form of one B vitamin in order to convert another B vitamin to its coenzyme form!

If you have only synthetic forms of these B vitamins, your body must go through multiple conversion processes in order to first convert synthetic Riboflavin into coenzyme Riboflavin so that you can convert synthetic vitamin B6 (Pyridoxine HCl) into its coenzyme B6 form (Pyridoxal-5′-Phosphate).

Yes, you can *survive* on synthetic forms of B vitamins. But why make your body work so hard? Why survive when you can *thrive* (with coenzyme vitamins)?

Why other kids vitamins don’t include coenzyme forms is BEYOND ME. If other brands go with conventional (and sometimes toxic) synthetic forms, so be it. Run, and go with Kids Mighty-Multi!.

Other advanced forms include vitamin D as D3 (cholecalciferol), vitamin K as K1 and K2 (Menaquinone-7), and minerals using Krebs’ cycle carriers (like citrates, malates, fumarates, succinates, and aspartates) that are best recognized and utilized in the body because they plug into the body’s energy (ATP) production system.

KIDS MIGHTY-MULTI!™ NUTRIENT TABLE

NUTRIENT

AMOUNT

% Daily Value

Vitamin A
(as beta-carotene from Dunaliella salinas)
470 IU 10
Vitamin C
(from potassium, magnesium, and calcium ascorbates)
16 mg 27
Vitamin D3 (as cholecalciferol) 50 IU 13
Vitamin E (from d-alpha tocopheryl succinate and 5 mg natural mixed tocopherols) 13 IU 42
Vitamin K (10 mcg as phylloquinone (K1) and 5 mcg as MK-7 (K2)) 15 mcg 18
Vitamin B1 (from thiamin diphosphate) 1.6 mg 107
Vitamin B2 (from riboflavin-5′-phosphate) 1.6 mg 94
Vitamin B3 (80% from niacinamide and 20% from niacin) 12 mg 60
Pantothenic Acid (from calcium pantothenate) 5 mg 50
Vitamin B6 (from pyridoxal-5′-phosphate) 2.5 mg 125
Vitamin B12 (as methylcobalamin) 15 mcg 250
Folate (from 5-MTHF – Quatrefolic®†) 50 mcg 13
Biotin (pure crystalline) 30 mcg 10
Magnesium (from malate) 6 mg 1.5
Calcium (from Krebs cycle bionutrients) 6 mg 0.6
Potassium (from citrate) 4.7 mg <1
Zinc (from citrate) 1.25 mg 8.3
Iron (from fumarate) 0.3 mg 1.7
Manganese (from citrate) 0.3 mg 15
Copper (from aspartate) 0.125 mg 6.3
Chromium (from polynicotinate) 13 mcg 11
Molybdenum (from citrate) 6 mcg 8
Selenium (from l-selenomethionine) 5 mcg 7
Choline (from bitartrate) 6 mg *
Inositol (pure crystalline) 15 mg *
N-Acetyl-L-Cysteine (NAC) 5 mg *
L-Taurine 5 mg *
Betaine HCl 3 mg *
Quercetin (as dihydrate) 3 mg *
Turmeric (from Curcuma longa) (root) 3 mg *
Broccoli Sprouts Powder 2 mg *
Grape Extract (Vitis vinifera) (from seed, skin, and stem) 1 mg *
Lycopene (tomato extract) (fruit) 200 mcg *
Boron (from glycinate and aspartate) 125 mcg *
Lutein (from Calendula officinalis) (flower) 70 mcg *
Octacosanol (from policosanol) 15 mcg *
Vanadium (from BGOV – bis glycinato oxo vanadium) 6 mcg *

* No established Daily Value
† Quatrefolic® is a registered trademark of Gnosis SPD

SCALABLE DOSING – CALLING ALL KIDS – AND ADULTS!

Maybe the best feature of Kids Mighty-Multi! is scalable dosing. Scalability makes it suitable for children and youth of all sizes—and adults, too!

Glancing at Kids Mighty-Multi!‘s label, you might assume it’s as low potency as the most kids’ vitamins available in stores. Not so fast.

Because Dr. Hank designed this multivitamin for everyone, including adults. How do I know? Because he told me: he takes these chewables himself!

How does it work? You simply take two (2) tablets per 20 pounds of body weight—up to six tablets—for kids. But since most older kids and adults weigh more than 60 pounds, you can take 8–10+ tablets and approximate the nutrition you would get from your regular adult vitamin. How cool is that!

Scalable dosing works well for people who don’t like swallowing capsules or tablets, or who prefer a good-tasting chewable. And who doesn’t, sometimes? It is especially useful for traveling because the entire family can use it.

In my case, I usually take four capsules per day of Hank & Brian’s Mighty Multi-Vite! , which my favorite adult multivitamin, and the inspiration for creating the Kids Mighty-Multi!. Yet, there are many days when I thrill to the taste of the new chewable kids multivitamin—knowing I get a significant amount of nutritional value. That means a lot. A lot of goodness. And not much to worry about.

Chewable Kids Mighty-Multi! multivitamin

Dr. Hank Liers pulled out the stops in formulating Kids Mighty-Multi!

CHOOSE KIDS MIGHTY-MULTI!

You’ve got choices. You can go online or to your local natural market, pharmacy, or big box store and fill up on whatever kids vitamins you find. Take your chances. Or you can try Kids Mighty-Multi! to discover how good a children’s multivitamin can (and should) be—a truly superior formula.

Choose our awesome kids multivitamin. Dr. Hank did his job. We’re 110% confident it meets—or exceeds—the needs and expectations of your child, and likely you, too. And definitely those of your clients, if you’re a health professional.

Of course, you’ve got a brain. But this choice is a “no-brainer.” Go for Kids Mighty Multi!. Your kids will never go back to their old multivitamin. And they’ll be healthier for it.

 

SOURCES & RESOURCES

Products

Kids Mighty-Multi! Multivitamin

HPDI Multivitamins

References

Coenzyme Vitamins (HPDI)

Fructooligosaccharides Abstracts (HPDI)

Statement on Additives (Excipients) (HPDI)

The HPDI Difference: Four Pillars of Excellence

Percent Daily Values (DV) Calculation Table (FDA)

Xylitol.org

Dr. Frank’s No-Aging Diet
by Benjamin S. Frank, MD, PhD

Studies

Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro.” Res Commun Mol Pathol Pharmacol. 95(2):179-89.
(Study includes mannitol benefits)

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PRO-C AND ULTIMATE PROTECTOR – COMPARISON OF ANTIOXIDANT FORMULAS

Dr. Hank Liers, PhD antioxidant formulasI have written extensively regarding the benefits HPDI’s PRO-C™ and Ultimate Protector™ antioxidant formulas. Based upon my experience with these formulas they are among the most effective antioxidant formulas available.

Both antioxidant formulas are included in HPDI’s system of foundational supplements and work most effectively when used with multivitamins, essential fats, and superfoods.

Yet, both formulas also are excellent standalone products that can rapidly provide the body with extremely high protection against free radicals.
Ultimate Protector antioxidant formulas

We are often asked “which of these two antioxidant formulas should I take?” My answer usually is to take both formulas. I personally take both of them on a daily basis.

Below I will briefly show the reason my answer is to take both formulas. I include information showing the relationship, in terms of ingredients of the two formulas (per serving of three (3) capsules daily of PRO-C and six (6) capsules daily of Ultimate Protector).

Ultimate Protector

INGREDIENTS OF ANTIOXIDANT FORMULAS

PRO-C™ (per serving of three “00” veggie caps)

• Buffered non-GMO Vitamin C (1,500 mg)  buffered with Ca/Mg/Zn
• Grape Extract (seed, skin, and pulp) (90 mg)
• Green Tea Extract 95% polyphenols 40% min. EGCG (90 mg)
• Glutathione – reduced (60 mg)
• N-Acetyl-l-Cysteine (NAC) (45 mg)
• R-Lipoic Acid (15 mg)
• Coenzyme B2/R5P (3 mg)
• Coenzyme B6/P5P (3 mg)
• Selenium from l-selenomethionine (30 mcg)
• Calcium (70 mg)
• Magnesium (70 mg)
• Zinc (6 mg)

ULTIMATE PROTECTOR™ (per serving of six “0” veggie caps)

• Vitamin C as non-GMO Ascorbic acid (1500 mg)
• Anthocomplete™ (135 mg)  Wild Blueberry, Wild Bilberry, Acai, Black Currant Extract, Sweet Cherry, Raspberry, Elderberry, Blackberry, Aronia, Black Soybean Hull Extract, and Blue Corn
• CoffeeBerry®Forte (135 mg)
• Vitaberry® Plus (90 mg) freeze-dried Grape Seed, Wild Blueberry, Wild Bilberry, Cranberry, Tart Cherry, Prune, Raspberry Seed, Strawberry, Trans-Resveratrol, and Quercetin
• VitaVeggie® (90 mg)  Broccoli, Broccoli Sprouts, Tomato, Kale, Carrot, Brussels Sprouts, Onion, and Spinach
• Curcumin 95%  (90 mg)
• Trans-Resveratrol 98% (90 mg)
• Malic Acid (500 mg)
• Calcium (60 mg)
• Magnesium (60 mg)
• BioPerine® (7.5 mg)

The products together contain nine (9) unique PRO-C™ ingredients, eight (8) unique Ultimate Protector™ ingredients, and three (3) overlapping ingredients.

DISCUSSION OF ANTIOXIDANT FORMULAS

PRO-C™

When PRO-C™ was first released in 1997 there were few publications available regarding Nrf2 ingredients and their benefits. The product design was based on the work of Dr. Lester Packer and his work done on the “Antioxidant Network” showing how nutrients such as Vitamin E, Vitamin C, Glutathione, and Lipoic acid work in a redox network to regenerate key nutrients in the body (see Figure 1. below)

doctor lester packer antioxidant formulas

                                                Figure 1. – Dr. Packer’s Antioxidant Network

At that time the powerful antioxidant formulas of Grape Seed Extract and Green Tea Extract were well known, but their powerful Nrf2 effects were not discovered until later. These ingredients are able to trap free radicals and conserve the body’s store of network antioxidants.

Also, the Nrf2 effects of NAC and Lipoic acid were not known at the time, but their powerful effects on the body were known to support the production of glutathione. Additionally, the super powerful glutathione (reduced) was included with supporting coenzymes B2 (from riboflavin 5′-phosphate) and B6 (from pyridoxal 5′-phosphate) that allow the enzymes glutathione reductase and transferase to function at a higher level.

ULTIMATE PROTECTOR™

From the beginning of the design process, Ultimate Protector™ (UP) was focused on creating a highly effective Nrf2 activator formula with outstanding antioxidant effects. Our understanding was that a very broad spectrum of plant polyphenols including flavonoids, anthocyandins, oligoproanthocyanidins (OPCs), etc. would deliver the best results.

We selected Futureceuticals Anthocomplete™, CoffeeBerry® Forte, Vitaberry® Plus, and VitaVeggie® in order to accomplish this and added Curcumin 95%, and Trans-Resveratrol 98% because of the powerful scientific findings regarding Nrf2 activation for these two ingredients. We found out later in testing that this combination of ingredients produces very high ORAC5.0 values (486,000 units/serving of six capsules) and works effectively against all of the primary types of free radicals in the body.

WHY TAKE BOTH PRO-C™ AND
ULTIMATE PROTECTOR™ ANTIOXIDANT FORMULAS?

Ultimate Protector versus PRO-C antioxidant formulas

Venn diagram showing unique and overlapping ingredients in PRO-C and Ultimate Protector.

There are 29 unique Nrf2 activator ingredients in Ultimate Protector (UP) and four (4) non-overlapping Nrf2 activator ingredients in PRO-C. Thus by taking both formulas you are able to receive 33 identifiable Nrf2 activator ingredients (870 mg). The amount of unique Nrf2 ingredients is probably significantly more than this because most of the identifiable ingredients contain a range of plant polyphenols.

Other unique ingredients of each formula include glutathione – reduced (60 mg), malic acid (500 mcg), zinc (6 mg), selenium (30 mcg), B2 (3 mg) and B6 (3 mg) from coenzyme forms, and Bioperine (7.5 mg) (for enhanced absorption of nutrients). These are important ingredients to have the formulas work more effectively together.

The overlapping ingredients in the formula include Vitamin C (3 gm – 1.5 gm from each formula), calcium (130 mg – 70 mg from PRO-C & 60 mg from UP), magnesium (130 mg – 70 mg from PRO-C & 60 mg from UP), and a little grape seed extract (~10 mg). We view this to be very positive especially because we believe that most people should take in at least 3 grams daily of Vitamin C. Equal amounts of calcium and magnesium balance each other in the body and have many important functions such as being part of critical enzymes.

SOURCES & RESOURCES

The Antioxidant Miracle. Lester Packer, PhD, and Carol Coleman. New York: John Wiley and Sons, 1999.

“Antioxidant Cocktail Update: Part 1: The Take Home Message is to Use Antioxidant Supplements”
(Interview of Dr. Lester Packer by Richard A. Passwater, PhD, Whole Foods Magazine, 1999)

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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.

I soon published several blog articles on this subject including a June 2012 article entitled New Directions For Preventing Free-Radical Damage and a July 2012 article entitled Natural Phytochemical Nrf2 Activators for Chemoprevention.

Also, I actively began the development of a new product called Ultimate Protector™ that contains many concentrates and extracts from fruits and vegetables. This product functions as 1) an excellent source of many Nrf2 activators contained in 29 different fruits and vegetables, 2) a source of powerful antioxidants exhibiting an ORAC5.0 value of 486,000 units in six small capsules, and 3) a source of non-GMO Vitamin C.

NRF2 Activators in Ultimate Protector

Ultimate Protector™ Nrf2 Activator Formula

In October 2012, I published a blog article titled Ultimate Protector™ Brunswick Labs ORAC5.0™ Test Results summarizing the laboratory test results that showed Ultimate Protector’s extremely high antioxidant values for the top five free-radical types found in the body.

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.”

Ultimate Protector NRF2 Activator ORAC

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 Nrf2 activator

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 6,300 5,900 2,500 106,000 52,000 173,000
Results are expressed in micro mole TE/g
4) Here is a list of the ingredients in ULTIMATE PROTECTOR™:  USP-grade non-GMO Buffered Vitamin C, AnthoComplete™ (high-ORAC powder from Wild Blueberry, Wild Bilberry, Acai, Black Currant Extract, Sweet Cherry, Raspberry, Elderberry, Blackberry, Aronia, Black Soybean Hull Extract, and Blue Corn), CoffeeBerry®Forte (high-ORAC powder from Coffee Berry), Curcumin (standardized extract with 95% curcuminoids), Trans-Resveratrol (98% from Giant Knotweed), VitaBerry®Plus (high-ORAC powder: from freeze-dried Grape Seed, Wild Blueberry, Wild Bilberry, Cranberry, Tart Cherry, Prune, Raspberry Seed, Strawberry, Trans-Resveratrol, and Quercetin), VitaVeggie® (high-ORAC powder from Broccoli, Broccoli Sprouts, Tomato, Kale, Carrot, Brussels Sprouts, Onion and Spinach), and Bioperine® (a patented black pepper extract that enhances absorption of all ingredients).

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

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