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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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ULTIMATE PROTECTOR INGREDIENTS – WILD BILBERRY AND WILD BLUEBERRY

Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicist wild bilberry and wild blueberry

Ultimate Protector contains wild bilberry and wild blueberry, as well as components from 29 different fruits, vegetables, and herbs. Each of these ingredients contain substances that may be considered to be polyphenols, antioxidants, and Nrf2 activators. In this article I will explore the ingredients wild bilberry and wild blueberry, which are components of Anthocomplete™ and VitaBerry Plus® from Futureceuticals.

ANTHOCOMPLETE™

AnthoComplete™ (N669) is a specially designed blend of anthocyanins derived from wild bilberry and wild blueberry, acai, black currant extract, sweet cherry, raspberry, elderberry, blackberry, aronia, black soybean hull extract, and blue corn. Anthocyanins are powerful plant polyphenols associated with a variety of areas of human health, including healthy aging, healthy glucose metabolism, cardiovascular health, and inflammation management.

Carefully designed to maximize the amount of beneficial anthocyanins that can be available in a single source, AnthoComplete is a proprietary formula suitable for a wide-range of applications.

With its diverse blend, AnthoComplete contains a minimum level of 10% anthocyanins, 3,000 ORAC μmole TE/g (typical), and 15% total phenolics (typical).

Bilberry / Blueberry wild bilberry and wild bluebery

VITABERRY PLUS®

VitaBerry® (N1023) is the trade name for a line of high ORAC blends of fruit powders and fruit extracts, exclusively available through FutureCeuticals.

VitaBerry® is a proprietary formula that combines wild bilberry and wild blueberry, cranberry, raspberry, strawberry, prune, cherry, and grape whole powders and extracts into lines of custom blends. High in fruit polyphenols, anthocyanins, proanthocyanins, ellagic acid, chlorogenic acid, resveratrol, and quinic acid, VitaBerry offers 6,000 ORAC units in a single gram.

VitaBerry® Plus (N81.3) combines the standard blend of VitaBerry® with resveratrol and quercetin to deliver a minimum of 12,000 ORAC units per gram.

HEALTH BENEFITS OF WILD BILBERRY AND WILD BLUEBERRY

Bilberry is any of several Eurasian  species of low-growing shrubs in the genus Vaccinium, bearing edible, nearly black berries. The species most often referred to is Vaccinium myrtillus L., but there are several other closely related species. Bilberries are distinct from blueberries but closely related. Whereas the bilberry is native to Europe, the blueberry is native to North America.

The bilberry fruit is smaller than that of the blueberry, but with a fuller taste. Bilberries are darker in color, and usually appear near black with a slight shade of purple. While blueberry fruit pulp is light green in color, bilberry is red or purple, heavily staining the fingers, lips, and tongue of consumers eating the raw fruit. The color comes from diverse anthocyanins.

So-called wild (lowbush) blueberries, smaller than cultivated highbush ones, are prized for their intense color. “Wild” has been adopted as a marketing term for harvests of managed native stands of lowbush blueberries. The bushes are not planted or genetically manipulated, but they are pruned or burned every two years, and pests are “managed”. The content of polyphenols and anthocyanins in lowbush (wild) blueberries (V. angustifolium) exceeds values found in highbush cultivars.

wild bilberry and wild blueberry

Wild bilberry and wild blueberry (above) provide Nrf2 activators.

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

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

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

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

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

Scientific Studies on the Antioxidant Effects of Wild Bilberry and Wild Blueberry

Databases of scientific studies (like the National Institutes of Health (NIH) PubMed database) contain thousands of up-to-date studies and abstracts about various Vaccinium species, including wild bilberry and wild blueberry (V. myrtillis and V. angustfolium, respectively).

We provide a few relevant scientific studies on the antioxidant effects of wild bilberry and wild blueberry.

In vitro anticancer activity of fruit extracts from Vaccinium species.

From: http://www.ncbi.nlm.nih.gov/pubmed/8693031

Abstract

Fruit extracts of four Vaccinium species (lowbush blueberry, bilberry, cranberry, and lingonberry) were screened for anticarcinogenic compounds by a combination of fractionation and in vitro testing of their ability to induce the Phase II xenobiotic detoxification enzyme quinone reductase (QR) and to inhibit the induction of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, by the tumor promoter phorbol 12-myristate 13-acetate (TPA). The crude extracts, anthocyanin and proanthocyanidin fractions were not highly active in QR induction whereas the ethyl acetate extracts were active QR inducers. The concentrations required to double QR activity (designated CDqr) for the ethyl acetate extracts of lowbush blueberry, cranberry, lingonberry, and bilberry were 4.2, 3.7, 1.3, and 1.0 microgram tannic acid equivalents (TAE), respectively, Further fractionation of the bilberry ethyl acetate extract revealed that the majority of inducer potency was contained in a hexane/chloroform subfraction (CDqr = 0.07 microgram TAE). In contrast to their effects on QR, crude extracts of lowbush blueberry, cranberry, and lingonberry were active inhibitors of ODC activity. The concentrations of these crude extracts needed to inhibit ODC activity by 50% (designated IC50) were 8.0, 7.0, and 9.0 micrograms TAE, respectively. The greatest activity in these extracts appeared to be contained in the polymeric proanthocyanidin fractions of the lowbush blueberry, cranberry, and lingonberry fruits (IC50 = 3.0, 6.0, and 5.0 micrograms TAE, respectively). The anthocyanidin and ethyl acetate extracts of the four Vaccinium species were either inactive or relatively weak inhibitors of ODC activity. Thus, components of the hexane/chloroform fraction of bilberry and of the proanthocyanidin fraction of lowbush blueberry, cranberry, and lingonberry exhibit potential anticarcinogenic activity as evaluated by in vitro screening tests.

 

Bilberry (Vaccinium myrtillus) anthocyanins modulate heme oxygenase-1 and glutathione S-transferase-pi expression in ARPE-19 cells.

From: http://www.ncbi.nlm.nih.gov/pubmed/17460300

Abstract

PURPOSE: To determine whether anthocyanin-enriched bilberry extracts modulate pre- or posttranslational levels of oxidative stress defense enzymes heme-oxygenase (HO)-1 and glutathione S-transferase-pi (GST-pi) in cultured human retinal pigment epithelial (RPE) cells.

METHODS: Confluent ARPE-19 cells were preincubated with anthocyanin and nonanthocyanin phenolic fractions of a 25% enriched extract of bilberry (10(-6)-1.0 mg/mL) and, after phenolic removal, cells were oxidatively challenged with H(2)O(2). The concentration of intracellular glutathione was measured by HPLC and free radical production determined by the dichlorofluorescin diacetate assay. HO-1 and GST-pi protein and mRNA levels were determined by Western blot and RT-PCR, respectively.

RESULTS: Preincubation with bilberry extract ameliorated the intracellular increase of H(2)O(2)-induced free radicals in RPE, though H(2)O(2) cytotoxicity was not affected. By 4 hours, the extract had upregulated HO-1 and GST-pi protein by 2.8- and 2.5-fold, respectively, and mRNA by 5.5- and 7.1-fold, respectively, in a dose-dependent manner. Anthocyanin and nonanthocyanin phenolic fractions contributed similarly to mRNA upregulation.

CONCLUSIONS: Anthocyanins and other phenolics from bilberry upregulate the oxidative stress defense enzymes HO-1 and GST-pi in RPE, suggesting that they stimulate signal transduction pathways influencing genes controlled by the antioxidant response element.

 

Berry anthocyanins suppress the expression and secretion of proinflammatory mediators in macrophages by inhibiting nuclear translocation of NF-κB independent of NRF2-mediated mechanism.

From: http://www.ncbi.nlm.nih.gov/pubmed/24565673

Abstract

The objectives of this study were to compare the anti-inflammatory effects of anthocyanins from blueberry (BBA), blackberry (BKA), and blackcurrant (BCA) and to determine the relationship between their antioxidant capacity and anti-inflammatory effect in macrophages. Major anthocyanins in BBA, BKA and BCA were malvidin-3-glucoside (16%), cyanidin-3-glucoside (98%) and delphinidin-3-rutinoside (44%), respectively. BKA showed higher total antioxidant capacity than BBA and BCA. RAW 264.7 macrophages were incubated with 0-20 μg/ml of BBA, BKA and BCA, and subsequently activated by lipopolysaccharide (LPS) to measure proinflammatory cytokine production. Interleukin 1β (IL-1β) messenger RNA (mRNA) levels were significantly decreased by all berry anthocyanins at 10 μg/ml or higher. Tumor necrosis factor α (TNFα) mRNA levels and secretion were also significantly decreased in LPS-treated macrophages. The levels of the repression were comparable for all berry anthocyanins. LPS-induced nuclear factor κB (NF-κB) p65 translocation to the nucleus was markedly attenuated by all of the berry anthocyanins. In bone marrow-derived macrophages (BMMs) from nuclear factor E2-related factor 2 wild-type (Nrf2(+/+)) mice, BBA, BKA and BCA significantly decreased cellular reactive oxygen species (ROS) levels with a concomitant decrease in IL-1β mRNA levels upon LPS stimulation. However, in the BMM from Nrf2(-/-) mice, the anthocyanin fractions were able to significantly decrease IL-1β mRNA despite the fact that ROS levels were not significantly affected. In conclusion, BBA, BKA and BCA exert their anti-inflammatory effects in macrophages, at least in part, by inhibiting nuclear translocation of NF-κB independent of the NRF2-mediated pathways.

 

Purified Anthocyanins from Bilberry and Black Currant Attenuate Hepatic Mitochondrial Dysfunction and Steatohepatitis in Mice with Methionine and Choline Deficiency

From: http://pubs.acs.org/doi/abs/10.1021/jf504926n

Abstract

The berries of bilberry and black currant are rich source of anthocyanins, which are thought to have favorable effects on non-alcoholic steatohepatitis (NASH). This study was designed to examine whether purified anthocyanins from bilberry and black currant are able to limit the disorders related to NASH induced by a methionine-choline-deficient (MCD) diet in mice. The results showed that treatment with anthocyanins not only alleviated inflammation, oxidative stress, steatosis and even fibrosis, but also improved the depletion of mitochondrial content and damage of mitochondrial biogenesis and electron transfer chain developed concomitantly in the liver of mice fed the MCD diet. Furthermore, anthocyanins treatment promoted activation of AMP-activated protein kinase (AMPK) and expression of peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α). These data provide evidence that anthocyanins possess significant protective effects against NASH and mitochondrial defects in response to a MCD diet, with mechanism maybe through affecting the AMPK/PGC-1α signaling pathways.

 

Effect of blueberry on hepatic and immunological functions in mice.

From: http://www.ncbi.nlm.nih.gov/pubmed/20382588

Abstract

Background: Conventional drugs used in the treatment and prevention of liver diseases often have side effects, therefore research into natural substances are of significance. This study examined the effects of blueberry on liver protection and cellular immune functions.

METHODS: To determine the effects of blueberry on liver protective function, male mice were orally administered blueberry (0.6 g/10 g) or normal saline for 21 days. Hepatic RNA was extracted by Trizol reagent, and the expression of Nrf2, HO-1, and Nqo1 was determined by real-time RT-PCR. Superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenate were determined, and liver index was measured. To assess the effects of blueberry on cellular immune function, male mice received blueberry (0.4, 0.6, or 0.8 g/10 g) for 35 days, and the percentages of CD3+, CD4+, and CD8+ T lymphocyte subgroups in peripheral blood were detected by flow cytometry, the index of the thymus and spleen was measured, and lymphocyte proliferation in the spleen was determined by MTT assay.

RESULTS: Blueberry treatment significantly increased the expression of Nrf2, HO-1, and Nqo1, the important antioxidant components in the liver. Hepatic SOD in the blueberry group was higher and MDA was lower than that in the control group (P<0.05). Blueberry also increased the index of the spleen and enhanced the proliferation of lymphocytes of the spleen (P<0.05). The percentages of the CD3+ and CD4+ T lymphocyte subsets and the CD4+/CD8+ ratio were also increased by blueberry (P<0.05).

CONCLUSIONS: Blueberry induces expression of Nrf2, HO-1, and Nqo1, which can protect hepatocytes from oxidative stress. In addition, blueberry can modulate T-cell function in mice.

 

Anthocyanins: Janus Nutraceuticals Displaying Chemotherapeutic and Neuroprotective Properties

From: http://link.springer.com/chapter/10.1007/978-94-007-4575-9_21

Abstract

Anthocyanins are natural polyphenolic compounds widely distributed as pigments in many fruits and vegetables. In addition to displaying antioxidant properties, these nutraceuticals exhibit anti-inflammatory, anti-proliferative, and pro-apoptotic activities suggesting their potential as novel chemotherapeutic agents. Through cell cycle down-regulation, and context-specific pro-oxidant activity, anthocyanins induce cytotoxicity in cancer cells in vitro and in vivo. Specifically, via regulation of the Bcl-2 protein family and induction of caspase-dependent or caspase-independent apoptotic pathways, anthocyanins inhibit the growth of cancers by inducing cell death. Moreover, by modulating the activities of specific kinases and proteases, including (but not limited to) cyclin-dependent kinases, mitogen-activated protein kinases, matrix metalloproteases, and urokinase-type plasminogen activators, anthocyanins induce apoptosis, inhibit motility, and suppress invasion of cancer cells. In marked contrast to their effects in cancer cells, we have found that anthocyanins display significant anti-apoptotic activity in neurons. Antioxidant properties of these nutraceuticals, particularly at the level of the mitochondria, appear to underlie their neuroprotective effects. The opposing effects of anthocyanins on cancer cells and neurons suggest that these nutraceuticals are promising candidates for development as either chemotherapeutic agents or novel neuroprotective compounds for the treatment of cancers or neurodegenerative diseases, respectively.

Recent Research on Polyphenolics in Vision and Eye Health

From: http://pubs.acs.org/doi/abs/10.1021/jf903038r#end-1

Abstract

A long-standing yet controversial bioactivity attributed to polyphenols is their beneficial effects in vision. Although anecdotal case reports and in vitro research studies provide evidence for the visual benefits of anthocyanin-rich berries, rigorous clinical evidence of their benefits is still lacking. Recent in vitro studies demonstrate that anthocyanins and other flavonoids interact directly with rhodopsin and modulate visual pigment function. Additional in vitro studies show flavonoids protect a variety of retinal cell types from oxidative stress-induced cell death, a neuroprotective property of significance because the retina has the highest metabolic rate of any tissue and is particularly vulnerable to oxidative injury. However, more information is needed on the bioactivity of in vivo conjugates and the accumulation of flavonoids in ocular tissues. The direct and indirect costs of age-related vision impairment provide a powerful incentive to explore the potential for improved vision health through the intake of dietary polyphenolics.

 

Bilberry Extracts Induce Gene Expression Through the Electrophile Response Element

From: http://www.tandfonline.com/doi/abs/10.1207/s15327914nc5401_11#.VLK6LVqBO24

Abstract

A number of genes important for detoxification and antioxidant defense induced by mild stress generated by, for example, physical activity/exercise, caloric restriction, or alcohol may provide health benefits by causing the organism to mount such a defense response. More recently, induction of these defenses has also been attributed to phytochemicals or secondary metabolites from dietary plants. Many polyphenols, which constitute a large fraction of these phytochemicals, increase cellular levels of antioxidants, such as glutathione and other components of the detoxification systems, via the transactivation of genes containing electrophile response elements (EpREs) within their promoters. One such gene, γ-glutamylcysteine synthetase, has previously been shown to be positively regulated by quercetin, a flavonoid found in high concentrations in onions, apples, and bilberries through EpRE transactivation. As a further step, we have investigated whether bilberries and quercetin have the ability to induce transcription of Fos-related antigen 1 (Fra-1), which contains two EpREs in its promoter. Fra-1 is a member of the activator protein 1 (AP-1) family of transcription factors and, due to the lack of transactivation domain Fra-1, can suppress activation of AP-1. We present results demonstrating that extracts from bilberries, and the flavonoid quercetin, abundant in bilberries, induce the fra-1 promoter and the cellular content of Fra-1 mRNA. We further provide evidence that this induction is mediated through EpREs.

 

Bilberry (Vaccinium myrtillus)

From: http://www.sigmaaldrich.com/life-science/nutrition-research/learning-center/plant-profiler/vaccinium-myrtillus.html

Synonyms / Common Names / Related Terms
Airelle, anthocyanins, Bickbeere (German), bilberry leaf, black whortle, Blaubeere (Dutch), blaubessen, bleaberry, blueberry, blueberry leaf, bogberry, bog bilberry, burren myrtle, cranberry, dwarf bilberry, dyeberry, Ericaceae (family), European blueberry, Heidelbeere (Dutch), Heidelbeereblatter, heidelberry, huckleberry, hurtleberry, lingonberry, lowbush blueberry, Mirtillo nero (Italian), Myrtilli folium, Myrtilli fructus, Myrtilus niger Gilib., Optiberry, resveratrol, sambubiosides, trackleberry, Vaccinium angulosum Dulac, Vaccinium montanum Salibs., Vaccinium myrtillus anthocyanoside extract, VMA extract, VME, whortleberry, wineberry
Mechanism of Action

Pharmacology:

  • Constituents: Bilberry contains several compounds that have demonstrated biological activity. The main chemicals contained in bilberry extract have been shown to be: anthocyanins30,31, flavonoids, hydroquinone, oleanolic acid, neomyrtillin, sodium, tannins, and ursolic acid17,20,32,33,34. Bilberry also contains resveratrol.28,29 The anthocyanosides, tannins, and flavonoids have been of particular scientific interest. Flavonoids have been shown in vitro to possess a number of biological properties, including inhibition of prostacyclin synthesis, reduction of capillary permeability and fragility, free radical scavenging, inhibition of a wide range of enzymes, impairment of coagulation and platelet aggregation, and anticarcinogenicity.33,5
  • Mechanism of action: Anthocyanins and other phenolics from bilberry upregulate the oxidative stress defense enzymes heme-oxygenase-1 and glutathione S-transferase-pin cultured human retinal pigment epithelial cells, suggesting that they stimulate signal transduction pathways, influencing genes controlled by the antioxidant response element.30
  • Antibacterial effects: In an in vitro study using Staphylococcus aureus, Staphylococcus aureus Oxford, Enterococcus faecalisBacillus subtilis, and Escherichia coli, an aqueous extract of bilberry leaves had a MIC of 12.7-17.8mg/mL and an aqueous extract of bilberry fruit had a MIC of 15.4-30.7mg/mL.24
  • Anticarcinogenic effects: In an in vitro study, anthocyanin-rich extracts from bilberry (Vaccinium myrtillus L.) inhibited the growth of a colon cancer cell line.6
  • Bomser et al. screened fruit extracts of bilberry for potential anticarcinogenic compounds by a combination of fractionation and in vitro testing of their ability to induce the Phase 2 xenobiotic detoxification enzyme quinone reductase (QR) and to inhibit the induction of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, by the tumor promoter phorbol 12-myristate 13-acetate (TPA).5 The crude extracts, anthocyanin, and proanthocyanidin fractions were not found to be highly active in Phase 2 xenobiotic detoxification enzyme quinone reductase (QR) induction, whereas the ethyl acetate extracts were active QR inducers. The concentrations required to double QR activity (designated CDqr) for the ethyl acetate extracts of bilberry were 1.0mcg tannic acid equivalents (TAE). Further fractionation of the bilberry ethyl acetate extract revealed that the majority of inducer potency was contained in a hexane/chloroform subfraction (CDqr = 0.07mcg TAE). The anthocyanidin and ethyl acetate extracts of bilberry were either inactive or relatively weak inhibitors of ornithine decarboxylase (ODC) activity. The authors concluded that components of the hexane/chloroform fraction of bilberry exhibit potential anticarcinogenic activity, as evaluated by in vitro screening tests.
  • Antihyperglycemic effects: In normal and depancreatized dogs, oral administration of bilberry leaves reduced hyperglycemia, even when the glucose was injected intravenously concurrently.15,16
  • Antioxidant effects: Bilberry contains anthocyanosides that are flavonoid derivatives of anthocyanins (the blue, red, or violet pigments found in many berry varieties), which are closely related in structure and activity to flavonoids17 and possess free radical scavenging/antioxidant properties. Antioxidant properties have been attributed to bilberry based on in vitro studies.1,2,34
  • Antiplatelet activity: In a clinical study of 30 subjects with normal platelet aggregation, 480mg of Myrtocyan® (Vaccinium myrtillus anthocyanins) daily, 3g of ascorbic acid daily, or both treatments all reduced platelet aggregation after 30 and 60 days.11 Bilberry anthocyanins reduced platelet aggregation more than ascorbic acid alone, but bilberry anthocyanins and ascorbic acid together were the most effective. Also, in in vitro studies, anthocyanins extracted from bilberry have inhibited platelet aggregation.13,14,10,12
  • Flavonoids have been shown in vitro to inhibit prostacyclin synthesis. In one animal model, Vaccinium myrtillus anthocyanosides were studied for their effects on prostacyclin-like activity in rat arterial issue.7
  • Antiproliferative effects: According to one laboratory study, anthocyanins were the predominant phenolic compounds in bilberry extracts.31 Compared to other plants with anthocyanins, such as black currant or lingonberry, cell growth inhibition was greater for bilberry than other plants studied. The pro-apoptosis marker, Bax, was increased 1.3-fold in bilberry-treated cells, whereas the pro-survival marker, Bcl-2, was detected only in control cells. The results demonstrated that bilberry and other berry extracts containing anthocyanins inhibited cancer cell proliferation, mainly via the p21WAF1 pathway.
  • Antiulcer effects: In an animal study, large doses of cyanidin chloride from bilberry significantly increased gastric mucosal release of prostaglandin E2.19 In animal models of gastric ulcers, cyanidin chloride showed antiulcer activity.26,8
  • Astringent effects: Bilberry contains tannins that have been used medicinally as astringents and to treat diarrhea.
  • Connective tissue stabilizing effects: An in vitro study has suggested that anthocyanosides appear to stabilize connective tissue by enhancing collagen synthesis, inhibiting collagen degradation, and enhancing collagen cross linking.35 In contrast, Boniface et al. found a significant decrease in connective tissue synthesis (collagen and glycoproteins) in gingival tissue samples of 12 adult diabetics treated with 600mg of anthocyanosides daily for two months.36
  • Hepatoprotective activity: In an animal study, anthocyans exerted a protective effect on liver cells.27
  • Hyperglycemic effects: In an oral glucose tolerance test in healthy rats, an alcoholic extract of Vaccinium myrtillus leaves increased serum glucose levels compared to controls.25
  • Hypotensive effects: Bilberry has been theorized to potentially drop blood pressure, based on pre-clinical evidence of vascular smooth muscle-relaxing properties.21,22,23
  • Anthocyanoside extracts have been shown to have smooth muscle-relaxing activity, which may account for their purported effects in one series of women with dysmenorrhea.18 Bioflavonoids and extracts of anthocyanosides (such as those present in bilberry) have been shown to relax vascular smooth muscles in experimental models, possibly via stimulation of prostaglandins.21,22,23
  • Intracellular signaling effects: Anthocyanosides have been shown to inhibit cAMP phosphodiesterase, which is involved in intracellular signal transduction pathways.8
  • Ocular effects: Anthocyanosides have been shown to exert direct effects on the retina, including the alteration of local enzymatic reactions and enhancement of the recovery of rhodopsin.9 The multi-ingredient product Mirtogenol (Pycnogenol® – French maritime pine bark extract and Mirtoselect® – standardized bilberry extract) has been reported to lower intraocular pressure and improve ocular blood flow.37
  • Smooth muscle relaxant effects: Anthocyanoside extracts have been shown to have smooth muscle-relaxing activity, which may account for their purported effects in one series of women with dysmenorrhea.18 Bioflavonoids and extracts of anthocyanosides (such as those present in bilberry) have been shown to relax vascular smooth muscles in experimental models, possibly via stimulation of prostaglandins.21,22,23
  • Vasoprotective effects: Flavonoids have been shown in vitro to reduce capillary permeability and fragility. Anthocyanosides have been studied for their potential protective effect in disorders due to abnormal capillary fragility.33

Pharmacodynamics/Kinetics:

  • There are limited data regarding the pharmacodynamics and kinetics of Vaccinium myrtillus (bilberry) anthocyanosides (VMA). In one animal study, bilberry anthocyanosides were rapidly distributed after intra-peritoneal injection and intravenous administration.38 In another animal study, bilberry anthocyanosides were found to be eliminated via the bile and urine with a modest level of liver extraction.32
  • Bioavailability in animals is low. Following oral doses in rats, plasma levels of VMA reached a peak at 15 minutes and declined rapidly within two hours, and the absolute bioavailability was 1.2% of the administered dose.38 The gastrointestinal absorption of VMA was 5% of the administered dose. Another study found a differential affinity of VMA for certain tissues (especially skin and kidney).20 This suggests that different tissues may have more persistent local concentrations.
References:

  1. Martin-Aragon S, Basabe B, Benedi JM, and et all. In vitro and in vivo antioxidant properties of Vaccinium myrtillus. Pharmaceutical Biology 1999;37(2):109-113.
  2. Prior R, Cao G, Martin A, and et all. Antioxidant capacity as influence by total phenolic and anthocyanin content, maturity, and variety of Vaccinium species. J Agricult Food Chem 1998;46:2686-2693.
  3. Martin-Aragon S, Basabe B, Benedi J, and et all. Antioxidant action of Vaccinium myrtillus L. Phytotherapy 1998;46:S104-S106.
  4. Laplaud, P. M., Lelubre, A., and Chapman, M. J. Antioxidant action of Vaccinium myrtillus extract on human low density lipoproteins in vitro: initial observations. Fundam Clin Pharmacol 1997;11(1):35-40. 9182074
  5. Bomser, J., Madhavi, D. L., Singletary, K., and Smith, M. A. In vitro anticancer activity of fruit extracts from Vaccinium species. Planta Med 1996;62(3):212-216.
  6. Zhao, C., Giusti, M. M., Malik, M., Moyer, M. P., and Magnuson, B. A. Effects of commercial anthocyanin-rich extracts on colonic cancer and nontumorigenic colonic cell growth. J Agric Food Chem  10-6-2004;52(20):6122-6128. 15453676
  7. Morazzoni P and Magistretti MJ. Effects of Vaccinium myrtillus anthocyanosides on prostacyclin-like activity in rat arterial issue. Fitoterapia 1986;57:11-14.
  8. Magistretti, M. J., Conti, M., and Cristoni, A. Antiulcer activity of an anthocyanidin from Vaccinium myrtillus. Arzneimittelforschung  1988;38(5):686-690. 3415709
  9. Cluzel, C., Bastide, P., Wegman, R., and Tronche, P. [Enzymatic activities of retina and anthocyanoside extracts of Vaccinium myrtillus (lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, 6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, alpha-glycerophosphate dehydrogenase, 5-nucleotidase, phosphoglucose isomerase)]. Biochem Pharmacol 1970;19(7):2295-2302. 4329039
  10. Morazzoni P and Bombardelli E. Vaccinium myrtillus L. Fitoterapia 1996;66:3-29.
  11. Pulliero G, Montin S, Bettini V, and et al. Ex vivo study of the inhibitory effects of Vaccinium myrtillus anthocyanosides on human platelet aggregation. Fitoterapia 1989;60:69-75.
  12. Bottecchia D. Preliminary report on the inhibitory effect of vaccinium myrtillus anthocyanosides on platelet aggregation and clot retraction. Fitoterapia 1987;48:3-8.
  13. Zaragoza, F., Iglesias, I., and Benedi, J. [Comparative study of the anti-aggregation effects of anthocyanosides and other agents]. Arch Farmacol Toxicol 1985;11(3):183-188. 4096552
  14. Fdez, M., Zaragoza, F., and Alvarez, P. In vitro platelet aggregation effects of anthocyanosides of vaccinium myrtilus L. Anales de la Real Academia de Farmacia 1983;49:79-90.
  15. Bever B. Plants with oral hypoglycemic action. Q J Crude Drugs Res 1979;17:139-196.
  16. Allen, F. M. Blueberry leaf extract: Physiologic and clinical properties in relation to carbohydrate metabolism. 89:1577-81, 1927. JAMA 1927;89:1577-1581.
  17. Havsteen, B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol 4-1-1983;32(7):1141-1148. 6342623
  18. Colombo D and Vescovini R. Controlled clinical trial of anthocyanosides from Vaccinium myrtillus in primary dysmenorrhea. G Ital Obstet Ginecol 1985;7:1033-1038.
  19. Mertz-Nielsen, A., Munck, L. K., Bukhave, K., and Rask-Madsen, J. A natural flavonoid, IdB 1027, increases gastric luminal release of prostaglandin E2 in healthy subjects. Ital J Gastroenterol  1990;22(5):288-290. 2134327
  20. Lietti, A., Cristoni, A., and Picci, M. Studies on Vaccinium myrtillus anthocyanosides. I. Vasoprotective and antiinflammatory activity. Arzneimittelforschung 1976;26(5):829-832. 9100
  21. Colantuoni, A., Bertuglia, S., Magistretti, M. J., and Donato, L. Effects of Vaccinium Myrtillus anthocyanosides on arterial vasomotion. Arzneimittelforschung  1991;41(9):905-909. 1796918
  22. Bettini V. Effects of Vaccinium myrtillus anthocyanosides on vascular smooth muscle. Fitoterapia 1984;55(5):265-272.
  23. Bettini V, Mayellaro F, Ton P, and et al. Interactions between Vaccinium myrtillusanthocyanosides and serotonin on splenic artery smooth muscle. Fitoterapia 1984;55(4):201-208.
  24. Brantner, A. and Grein, E. Antibacterial activity of plant extracts used externally in traditional medicine. J Ethnopharmacol 1994;44(1):35-40. 7990502
  25. Neef H, Declercq P, and Laekeman G. Hypoglycaemic activity of selected European plants. Phytotherapy Research 1995;9:45-48.
  26. Cristoni, A. and Magistretti, M. J. Antiulcer and healing activity of Vaccinium myrtillus anthocyanosides. Farmaco [Prat] 1987;42(2):29-43. 3582621
  27. Mitcheva, M., Astroug, H., Drenska, D., Popov, A., and Kassarova, M. Biochemical and morphological studies on the effects of anthocyans and vitamin E on carbon tetrachloride induced liver injury. Cell Microbiol 1993;39(4):443-448. 8329983
  28. Lyons, M. M., Yu, C., Toma, R. B., Cho, S. Y., Reiboldt, W., Lee, J., and van Breemen, R. B. Resveratrol in raw and baked blueberries and bilberries. J Agric Food Chem  9-24-2003;51(20):5867-5870. 13129286
  29. Rimando, A. M., Kalt, W., Magee, J. B., Dewey, J., and Ballington, J. R. Resveratrol, pterostilbene, and piceatannol in vaccinium berries. J Agric Food Chem 7-28-2004;52(15):4713-4719. 15264904
  30. Milbury, P. E., Graf, B., Curran-Celentano, J. M., and Blumberg, J. B. Bilberry (Vaccinium myrtillus) anthocyanins modulate heme oxygenase-1 and glutathione S-transferase-pi expression in ARPE-19 cells. Invest Ophthalmol Vis Sci 2007;48(5):2343-2349. 17460300
  31. Wu, Q. K., Koponen, J. M., Mykkanen, H. M., and Torronen, A. R. Berry phenolic extracts modulate the expression of p21(WAF1) and Bax but not Bcl-2 in HT-29 colon cancer cells. J Agric Food Chem 2-21-2007;55(4):1156-1163. 17243699
  32. Lietti, A. and Forni, G. Studies on Vaccinium myrtillus anthocyanosides. II. Aspects of anthocyanins pharmacokinetics in the rat. Arzneimittelforschung  1976;26(5):832-835. 989354
  33. Mian E. Anthocyanosides and microvessel walls: new findings on the mechanism of action of their protective effect in syndromes due to abnormal capillary fragility. Minerva Med 1977;68(52):3565-3581.
  34. Marcollet M, Bastide P, and Tronche P. Effet angio-protecteur des anthocyanosides de Vaccinium myrtillus odjective vis a vis de la liberation de la lactate deshydrogenase (LDH) et de ses isoenzymes cardiaques chez le rat soumis a une epreuve de nage. C R Soc Biol  1970;163:1786.
  35. Jonadet, M., Meunier, M. T., Bastide, J., and Bastide, P. [Anthocyanosides extracted from Vitis vinifera, Vaccinium myrtillus and Pinus maritimus. I. Elastase-inhibiting activities in vitro. II. Compared angioprotective activities in vivo]. J Pharm Belg 1983;38(1):41-46. 6553084
  36. Boniface, R. and Robert, A. M. [Effect of anthocyanins on human connective tissue metabolism in the human]. Klin Monatsbl Augenheilkd  1996;209(6):368-372. 9091714
  37. Steigerwalt, R. D., Gianni, B., Paolo, M., Bombardelli, E., Burki, C., and Schonlau, F. Effects of Mirtogenol on ocular blood flow and intraocular hypertension in asymptomatic subjects. Mol Vis  2008;14:1288-1292. 18618008
  38. Morazzoni, P., Livio, S., Scilingo, A., and Malandrino, S. Vaccinium myrtillus anthocyanosides pharmacokinetics in rats. Arzneimittelforschung  1991;41(2):128-131. 2043174

SUMMARY

Wild bilberries and wild blueberries are important fruits full of polyphenols, anthocyanins, antioxidants, and Nrf2 activators that help to make Ultimate Protector such an outstanding nutritional supplement.

 

up-4 elderberry wild bilberry and wild blueberry

Ultimate Protector provides wild bilberry and wild blueberry, and 27 other Nrf2 activator-containing plant-based ingredients.

ADDITIONAL RESOURCES