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

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

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

homocysteine metabolism diagram

Figure 1. Metabolic Pathways in Methionine and Homocysteine Metabolism


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

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


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

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

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

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

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


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

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

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

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

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


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





The Homocysteine Revolution by Kilmer S. McCully, MD

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


(coenzyme folate)

(vitamin B12)


HPDI Multivitamins



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!


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.


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).


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


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.


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.)


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.




% 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


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!


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.




Kids Mighty-Multi! Multivitamin

HPDI Multivitamins


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)


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


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)



Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicist strawberriesUltimate Protector™ contains freeze dried strawberries, 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 explore the ingredient strawberries, which is a component of VitaBerry Plus® from Futureceuticals.


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.

Strawberry strawberries


Strawberries long have grown wild in the world’s temperate regions. They have been cultivated for several thousand years and were prized among the ancient Romans. Most of the common varieties of strawberry derive from a hybrid (Frangaria x ananassa). Strawberries have an ORAC value of 1,540, which is very high among the fruits and vegetables tested by the USDA. They are a good source of vitamins C, K, B2, B5, B6, and folate. They also contain appreciable amounts of the minerals manganese, iodine, and potassium, as well as dietary fiber.

Like other berries, the antioxidants contained in strawberries may be useful against diseases of the heart and arteries by preventing the oxidation of lipids. The phytonutrient phenols most abundant in strawberries are anthocyanins and ellagitannins. The anthocyanins help to prevent oxidative damage from free radicals in body. The unique phenol profile of the strawberry enables it not only to protect the heart, but also to fight inflammation. Studies have shown that strawberries also protect the brain from oxidative stress and may therefore reduce age-related cognitive decline in brain function. Strawberries have been shown to be Nrf2 activators that can stimulate the endogenous production of protective enzymes in the body.

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

  • Anthocyanins
    • cyanidins
    • pelargonidins
  • Flavonols
    • procyanidins
    • catechins
    • gallocatechins
    • epicatechins
    • kaempferol
    • quercetin
  • Hydroxy-benzoic acids
    • ellagic acid
    • gallic acid
    • vanillic acid*
    • salicylic acid
  • Hydroxy-cinnamic acids
    • cinnamic acid
    • coumaric acid
    • caffeic acid
    • ferulic acid
  • Tannins
    • ellagitannins
    • gallotannins
  • Stilbenes
    • resveratrol

For more information on strawberries visit: http://www.whfoods.com/genpage.php?tname=foodspice&dbid=32

Scientific Studies on the Antioxidant Effects of Strawberries

Below, I provide relevant scientific studies on the antioxidant effects and potential health benefits of strawberries.

Strawberry as a functional food: an evidence-based review

From: http://www.ncbi.nlm.nih.gov/pubmed/24345049


Emerging research provides substantial evidence to classify strawberries as a functional food with several preventive and therapeutic health benefits. Strawberries, a rich source of phytochemicals (ellagic acid, anthocyanins, quercetin, and catechin) and vitamins (ascorbic acid and folic acid), have been highly ranked among dietary sources of polyphenols and antioxidant capacity. It should however be noted that these bioactive factors can be significantly affected by differences in strawberry cultivars, agricultural practices, storage, and processing methods: freezing versus dry heat has been associated with maximum retention of strawberry bioactives in several studies. Nutritional epidemiology shows inverse association between strawberry consumption and incidence of hypertension or serum C-reactive protein; controlled feeding studies have identified the ability of strawberries to attenuate high-fat diet induced postprandial oxidative stress and inflammation, or postprandial hyperglycemia, or hyperlipidemia in subjects with cardiovascular risk factors. Mechanistic studies have elucidated specific biochemical pathways that might confer these protective effects of strawberries: upregulation of endothelial nitric oxide synthase (eNOS) activity, downregulation of NF-kB activity and subsequent inflammation, or inhibitions of carbohydrate digestive enzymes. These health effects may be attributed to the synergistic effects of nutrients and phytochemicals in strawberries. Further studies are needed to define the optimal dose and duration of strawberry intake in affecting levels of biomarkers or pathways related to chronic diseases.

Bioactive Compounds and Antioxidant Activity in Different Types of Berries


Berries, especially members of several families, such as Rosaceae (strawberry, raspberry, blackberry), and Ericaceae (blueberry, cranberry), belong to the best dietary sources of bioactive compounds (BAC). They have delicious taste and flavor, have economic importance, and because of the antioxidant properties of BAC, they are of great interest also for nutritionists and food technologists due to the opportunity to use BAC as functional foods ingredients. The bioactive compounds in berries contain mainly phenolic compounds (phenolic acids, flavonoids, such as anthocyanins and flavonols, and tannins) and ascorbic acid. These compounds, either individually or combined, are responsible for various health benefits of berries, such as prevention of inflammation disorders, cardiovascular diseases, or protective effects to lower the risk of various cancers. In this review bioactive compounds of commonly consumed berries are described, as well as the factors influencing their antioxidant capacity and their health benefits.

Dietary intakes of berries and flavonoids in relation to cognitive decline

From: http://www.ncbi.nlm.nih.gov/pubmed/22535616


Objective: Berries are high in flavonoids, especially anthocyanidins, and improve cognition in experimental studies. We prospectively evaluated whether greater long-term intakes of berries and flavonoids are associated with slower rates of cognitive decline in older women.

Methods: Beginning in 1980, a semiquantitative food frequency questionnaire was administered every 4 years to Nurses’ Health Study participants. In 1995–2001, we began measuring cognitive function in 16,010 participants, aged ≥70 years; follow-up assessments were conducted twice, at 2-year intervals. To ascertain long-term diet, we averaged dietary variables from 1980 through the initial cognitive interview. Using multivariate-adjusted, mixed linear regression, we estimated mean differences in slopes of cognitive decline by long-term berry and flavonoid intakes.

Results: Greater intakes of blueberries and strawberries were associated with slower rates of cognitive decline (eg, for a global score averaging all 6 cognitive tests, for blueberries: p-trend = 0.014 and mean difference = 0.04, 95% confidence interval [CI] = 0.01–0.07, comparing extreme categories of intake; for strawberries: p-trend = 0.022 and mean difference = 0.03, 95% CI = 0.00–0.06, comparing extreme categories of intake), after adjusting for multiple potential confounders. These effect estimates were equivalent to those we found for approximately 1.5 to 2.5 years of age in our cohort, indicating that berry intake appears to delay cognitive aging by up to 2.5 years. Additionally, in further supporting evidence, greater intakes of anthocyanidins and total flavonoids were associated with slower rates of cognitive decline (p-trends = 0.015 and 0.053, respectively, for the global score).

Interpretation: Higher intake of flavonoids, particularly from berries, appears to reduce rates of cognitive decline in older adults.

Addition of strawberries to the usual diet decreases resting chemiluminescence of fasting blood in healthy subjects-possible health-promoting effect of these fruits consumption

From: http://www.ncbi.nlm.nih.gov/pubmed/24912053


OBJECTIVE: Regular strawberry consumption augmented plasma antioxidant activity and decreased lipid peroxidation suggests preventive potential of these fruits against oxidative stress-dependent disorders. Blood phagocytes are important source of oxidants that may contribute to systemic oxidative stress. We examined the effect of strawberry consumption on the luminol enhanced whole blood chemiluminescence (LBCL) reflecting oxidants generation by circulating phagocytes in healthy subjects.

METHODS: Thirty-one healthy subjects (being on their usual diet) consumed 500 g of strawberry pulp daily (between 11.00-14.00) for 30 days (1st strawberry course) and after 10 day wash-out the cycle was repeated (2nd strawberry course). Fasting blood and spot morning urine samples were collected before and after each strawberry course for measuring resting and agonist (fMLP)-induced LBCL, various phenolics and plasma antioxidant activity. Twenty subjects served as a control in respect to LBCL changes over the study period.

RESULTS: Strawberry consumption decreased median resting LBCL and this effect was more evident after the 1st course (by 38.2%, p < 0.05) than after the the 2nd one (18.7%), while fMLP-induced LBCL was constant. No changes in LBCL were noted in controls. Strawberries increased fasting plasma levels of caffeic acid and homovanillic acid as well as urolithin A and 4-hydroxyhippuric acid in spot urine. Plasma antioxidant activity and the number of circulating phagocytes did not change over the study period. Resting LBCL correlated positively with the number of circulating polymorphonuclear leukocytes at all occasions and negative correlation with plasma 4-hydroxyhippuric acid was noted especially after the first strawberry course (r = -0.46, p < 0.05).

CONCLUSIONS: The decrease in resting LBCL suggests that regular strawberry consumption may suppress baseline formation of oxidants by circulating phagocytes. This may decrease the risk of systemic imbalance between oxidants and anti-oxidants and be one of mechanisms of health-promoting effect of these fruits consumption.

Consumption of strawberries on a daily basis increases the non-urate 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging activity of fasting plasma in healthy subjects

From: http://www.ncbi.nlm.nih.gov/pubmed/25120279


Strawberries contain anthocyanins and ellagitanins which have antioxidant properties. We determined whether the consumption of strawberries increase the plasma antioxidant activity measured as the ability to decompose 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) in healthy subjects. The study involved 10 volunteers (age 41 ± 6 years, body weight 74.4 ± 12.7 kg) that consumed 500 g of strawberries daily for 9 days and 7 matched controls. Fasting plasma and spot morning urine samples were collected at baseline, during fruit consumption and after a 6 day wash-out period. DPPH decomposition was measured in both deproteinized native plasma specimens and pretreated with uricase (non-urate plasma). Twelve phenolics were determined with HPLC. Strawberries had no effect on the antioxidant activity of native plasma and circulating phenolics. Non-urate plasma DPPH decomposition increased from 5.7 ± 0.6% to 6.6 ± 0.6%, 6.5 ± 1.0% and 6.3 ± 1.4% after 3, 6 and 9 days of supplementation, respectively. The wash-out period reversed this activity back to 5.7 ± 0.8% (p<0.01). Control subjects did not reveal any changes of plasma antioxidant activity. Significant increase in urinary urolithin A and 4-hydroxyhippuric (by 8.7- and 5.9-times after 6 days of supplementation with fruits) was noted. Strawberry consumption can increase the non-urate plasma antioxidant activity which, in turn, may decrease the risk of systemic oxidants overactivity.

One-month strawberry-rich anthocyanin supplementation ameliorates cardiovascular risk, oxidative stress markers and platelet activation in humans

From: http://www.ncbi.nlm.nih.gov/pubmed/24406274


Strawberries are an important fruit in the Mediterranean diet because of their high content of essential nutrients and beneficial phytochemicals, which seem to exert beneficial effects in human health. Healthy volunteers were supplemented daily with 500 g of strawberries for 1 month. Plasma lipid profile, circulating and cellular markers of antioxidant status, oxidative stress and platelet function were evaluated at baseline, after 30 days of strawberry consumption and 15 days after the end of the study. A high concentration of vitamin C and anthocyanins was found in the fruits. Strawberry consumption beneficially influenced the lipid profile by significantly reducing total cholesterol, low-density lipoprotein cholesterol and triglycerides levels (-8.78%, -13.72% and -20.80%, respectively; P<.05) compared with baseline period, while high-density lipoprotein cholesterol remained unchanged. Strawberry supplementation also significant decreased serum malondialdehyde, urinary 8-OHdG and isoprostanes levels (-31.40%, -29.67%, -27.90%, respectively; P<.05). All the parameters returned to baseline values after the washout period. A significant increase in plasma total antioxidant capacity measured by both ferric reducing ability of plasma and oxygen radical absorbance capacity assays and vitamin C levels (+24.97%, +41.18%, +41.36%, respectively; P<.05) was observed after strawberry consumption. Moreover, the spontaneous and oxidative hemolysis were significant reduced (-31.7% and -39.03%, respectively; P<.05), compared to the baseline point, which remained stable after the washout period. Finally, strawberry intake significant decrease (P<.05) the number of activated platelets, compared to both baseline and washout values. Strawberries consumption improves plasma lipids profile, biomarkers of antioxidant status, antihemolytic defenses and platelet function in healthy subjects, encouraging further evaluation on a population with higher cardiovascular disease risk.

Impact of strawberries on human health: insight into marginally discussed bioactive compounds for the Mediterranean diet


OBJECTIVE: To review and update the current knowledge on the potential impact of strawberry on human health, with particular attention on compounds and indirect mechanisms of action not exhaustively considered.

DESIGN: Personal perspectives and recent data.

SETTING: International.

RESULTS: Our research group was among the few groups that have recently investigated the folate content in fresh, stored and processed strawberries, and the data look very promising. As well, some in vivo evidence of the impact of strawberry intake on the folate status in humans have already been reported, but a new increasing interest on this field is strongly hoped. Furthermore, the hypouricaemic effects previously ascribed to cherry consumption need to be evaluated in respect to strawberry intake. At the moment, inconsistent results come from the few investigations designed at this proposal. In our studies, a great interindividual variability was observed on plasma urate levels in response to strawberry intake, suggesting a putative effect.

CONCLUSIONS: The mechanisms responsible for the potential health-promoting effects of strawberry may not be necessarily searched in the activity of phytochemicals. Particularly, a greater interest should be addressed to show whether a prolonged strawberry consumption may effectively improve the folate status and reduce the incidence of folate-related pathological conditions. Furthermore, the hypouricaemic effects of cherries need to be evaluated also in respect to strawberry intake, and the mechanisms of actions and anti-gout potentialities need to be studied in detail. Future investigations involving human trials should be aimed at following these underestimated scientific tracks.

strawberry strawberries fruit


Strawberries are an important fruit full of polyphenols, anthocyanins, antioxidants, and Nrf2 activators that help to make Ultimate Protector such an outstanding nutritional supplement.


Contact Us:

You can reach HPDI by calling 1-800-228-4265, email support(at)IntegratedHealth.com, or visit the retail website: www.IntegratedHealth.com

Health care professionals and retailers can apply for wholesale account, which includes access to the HPDI reseller website: www.HealthProductsDistributors.com


Frequently Asked Questions About Our Products

Dr. Hank Liers, PhD productsWe frequently receive questions about our products and share the answers with you on our blog. If you have questions please e-mail us at support(at)integratedhealth.com. We will answer your questions directly, and likely include your question and our answer in a future products FAQ blog article.



Q. How Much Protein is in Rejuvenate! Plus and What are the Sources?

Rejuvenate! PlusA. The protein (11.7 gm total per serving) profile in Rejuvenate! Plus is 30% rice protein (organic & non-GMO), 16% vegetable sprouts/pea protein (organic), 11% hemp protein (organic), 11% protein from chlorella, 9% protein from alfalfa grass, 7% from spirulina (Hawaii Pacifica), 6% from flax seeds (organic), 3% from nutritional yeast, and the rest from miscellaneous other ingredients. This is a beautiful blend of a large number of healthy protein sources!!

The rice protein we do use amounts to 5.0 gm per 31 gram serving and is a blend of 80% Orzatein (organic) from China and 47.5% non-gmo grown in California. The net amount of the 80% orzatein (organic) from China in the product is 3.3 grams (a small amount!). Please be advised that we routinely test Rejuvenate! Plus for heavy metals and have never seen significant amounts of any heavy metals.

Personally, four members of my family including me take 1 or 2 servings of Rejuvenate! Plus daily and have done so for many years with excellent results. We are very particular about the foods we put in our body!!

Q. What are the Sources of Enzymes, Soy, and Vitamin D3 in Rejuvenate! Plus?

A. The enzymes are plant based. Protease Enzymes from Aspergillus oryzae ferment. Cellulase Enzymes from Trichoderma oryzae ferment. Alpha-Galactosidase enzymes from Aspergillus niger ferment. CereCalase enzymes (contains hemicellulase, beta-glucanase & phytase) from Aspergillus niger ferment.

The product contains d-alpha tocopheryl succinate. This ingredient is characterized as “soy-antigen free” because of the way it is processed. PCR testing reveals no soy protein even though it originally comes from soy. High-gamma mixed tocopherols is characterized as “soy-antigen free” because of the way it is processed. PCR testing reveals no soy protein even though it originally comes from soy.

The Vitamin D3 is extracted from lanolin. Lanolin is extracted from wool (sheep).

Q. What Form of Vitamin B3 is in Rejuvenate! Plus and will It Cause Flushing?

A. There is 40 mg of the B3 in Rejuvenate! Plus as niacinamide. This form of B3 will not cause flushing.

Q. What Part of the Aloe Vera Plant is in Your Rejuvenate Plus Product?

A. Rejuvenate! Plus contains Organic ActivAloe® 200:1 from gel that is made into a powder.

Q. Do Your Rejuvenate! Products Contain Any Nut or Soy Allergens?

Rejuveante OriginalA. I checked with the manufacturer and was assured that there is no soy or nut allergens in the Rejuvenate, Rejuvenate Plus, or Rejuvenate Berries & Herbs products.

Q. How Do You Make Rejuvenate! Original Lemonade?

A. Rejuvenate! Original lemonade consists of one scoop of Rejuvenate! Original, 2–3 tablespoons of organic lemon juice (fresh or Santa Cruz brand), and 2–3 tablespoons of organic grade B maple syrup. Put these ingredients in a one-quart glass Mason jar and fill with purified water (and maybe some ice made from purified water). Some people like to add a bit of cayenne. This is a great summertime drink!

Q. How Much Rice Bran Oil is in Complete E?

A. There is approximately 250 mg of rice bran oils per capsule in addition to the Vitamin E. The profile of fatty acids is approximately 38% monounsaturated, 37% polyunsaturated, and 25% saturated fatty acids. This amounts to about 100 mg of polyunsaturated fatty acids per capsule. Very little, but useful!

Q. I Want to Know More About the Black Soybean Hull Extract in Ultimate Protector.

up-product-includesA. Black soybean hull extract contains a high percentage of polyphenols (greater than 60% and as high as 100%) including 10–45% anthocyanidins, 10–25% catechins, and 40–80% OPC. There is unlikely to be any soy protein or phytoestrogens in the product due to the extraction processes used. (See: http://www.google.com/patents/US8206764).

Q. I Want to know How Much Caffeine is in Ultimate Protector.

A. A study done on CoffeeBerry extract shows a 0.44% caffeine content. Since each capsule contains 45 mg of the extract the amount of caffeine per capsule is about 0.2 mg (or 1.2 mg per serving of 6 capsules). (See: http://www.nutritionaloutlook.com/news/study-compares-higher-antioxidant-coffee-fruit-extract-coffee-powder).

Q. I Want to Know More About the Blue Corn Extract in Ultimate Protector, and if it contains aspergillus mold.

A. Ultimate Protector contains an extract of blue corn optimized for the anthocyanidin content. Due to the extraction process, it is unlikely that the final material contains any aspergillus. Also, since there is only a small amount of blue corn extract in the product (I estimate less than 5 mg per capsule) it is even more unlikely that aspergillus is a problem.

Q. Does the Vitamin C in Ultimate Protector contain Genetically Modified Organisms (GMOs)?

A. The process of producing Vitamin C involves using the starting material of d-glucose derived from plant materials such as corn, beets, potatoes, cassava, etc. (See: http://en.wikipedia.org/wiki/Reichstein_process). Each of these starting materials will contain some protein that could be in part from genetically modified materials. In most cases—especially in the production of USP grade materials that we use in Ultimate Protector™—the protein will be completely removed. As a precaution that no genetically modified protein remains, PCR testing is conducted (See: http://www.nongmoproject.org/product-verification/about-gmo-testing/guidelines/). The Vitamin C we use in Ultimate Protector™ has been tested using this method, and is certified by independent laboratories to contain no GMOs.

Q. Is There Any Vitamin E in Ultimate Protector Product?

A. There is no Vitamin E in Ultimate Protector. The Vitamin C per cap is 250 mg which is 415% of the Vitamin C RDA. Once in the body, the Vitamin C is able to regenerate oxidized Vitamin E to its unoxidized form. The other main ingredients in Ultimate Protector are plant-based antioxidants (external) and other plant-based substances (called Nrf2 activators) that stimulate the body to make it own antioxidants (internal). In this regard, it is a very powerful supplement!

Q. What are the Plant Sources in Ultimate Protector that provide High ORAC5.0 Values?

A. There are six ingredients that provide high ORAC values. Three of these ingredients (AnthoComplete®, VitaBerry® Plus, and VitaVeggie®) are a mixture of extracts from a wide range of fruits and vegetables. Below each of the ingredients are listed along with website/product information:

1) AnthoComplete® from Futureceuticals (http://www.futureceuticals.com/products/anthocomplete™),
2) CoffeeBerry® Forte from Futureceuticals (http://www.futureceuticals.com/products/coffee-fruit),
3) VitaBerry® Plus from Futureceuticals (http://www.futureceuticals.com/products/vitaberry®),
4) VitaVeggie® from Futureceuticals (http://www.futureceuticals.com/products/vitaveggie®).
5) Resveratrol (98% min.) is derived from the Giant Knotweed (Polygonum cuspidatum)
6) Curcumin (95% min. curcuminoids) from Sabinsa (http://www.sabinsa.com/products/standardized-phytoextracts/c3/)

All of these sources are non-GMO. None of our sources claim organic. This in part may be because they are extracts and as such may have been processed in a manner not considered to be organic. Please consider that this is a nutritional supplement and not a food.

Q. What Form of 5-MTHF Do You Use in Your Products?

A. We use only the Quatrefolic form of folate made by the Italian company Gnosis. See: http://www.quatrefolic.com/4thGeneration.html. This contains only the active non-racemic form of folate and no folic acid. Quatrefolic®, provides the metabolic reduced form utilized and stored in the human body – (6S)-5-methyltetrahydrofolate.

Q. Why is the Number of Organisms in Your Prescript-Assist™ Formula Low Compared to Other Probiotics?

A. It turns out that it’s an example of the old story of trying to compare apples to oranges. SBO (soil-based organisms), the type found in Prescript Assist, are much more hardy and not destroyed as easily by pH differences in your stomach and intestines like the traditional lactic acid probiotics that have crowded the refrigerators in health food stores for many years.

Have you noticed that in recent years typical probiotics have gone from 5–10 million CFUs (Colony-Forming Units) to 30–50 million CFUs? Why are all of these probiotic formulas competing on this level? Because lactic-acid based probiotics are killed off by the millions on their journey through your stomach acids and the pH changes in the intestines. Very few make it to their intended target and even fewer colonize there very well once they make it compared to the sturdier SBOs.

Prescript AssistSoil-Based Organisms (SBO) are extremely hardy and can make this journey with far, far more organisms colonizing their target. They also do not degrade when kept at room temperature for many months. They do not have to be refrigerated like the traditional lactic acid probiotics, which lose their potency and effectiveness quickly when left unrefrigerated or when they are shipped through the mail without dry ice.

Prescript-Assist goes even a step further by providing prebiotics for the SBOs so that when they arrive in your lower intestinal tract, they have the preferred foods necessary for quick colonization and growth. The 29 strains they have chosen for this product are far more comprehensive than traditional probiotics that have 5–10 strains.

Q. Is Prescript-Assist Toxic?

A. Over the last 10 years a very large number of people have taken Prescript Assist with excellent results. The overall statistics say that it works and is generally safe.

It is true that some people have felt that Prescript-Assist has not helped them and in fact they may feel worse. My assessment of this is that these people have severe gut dysbiosis and experience die-off like symptoms upon taking it. These individuals need to go more slowly and do a detoxification/cleansing program while using Prescript Assist. I recommend taking supplements such as HPDI’s Intestinal Rejuvenation Formula, digestive enzymes (Prolyt and Digase), and Dr. Richard Schultze’s Intestinal Formula #1 (if you are blocked, i.e., sluggish bowel).

Also, doing a juice flush could be important. So many people have a lifetimes’s buildup of fecal matter in their systems. Taking a single pill alone is not the solution. Doing an overall cleansing and having a good nutritional program is important for most people. Some professionals recommend that after an initial round of Prescript-Assist you only need to take a few capsules per week to maintain a healthy gut bacteria profile. You can read more about it here: http://www.prescript-assist.com/products/?gclid=CNSBvs7m3cUCFUuTfgodSp8AqQ

Q. What is the Purity of Fish Liver Oil in Your Vitamin D3 Plus Product?

Vitamin D3 PlusA: I am always careful when formulating any product to minimize any potential toxins. Vitamin D3 and Vitamin A from fish liver oils, as are found in the HPDI Vitamin D3 Plus formula, are highly concentrated sources which means that only milligram amounts are needed. This in itself means that there would be very low levels of toxins. This is verified by testing that shows mercury levels of less than 0.003 ppm, lead levels of less than 0.005 ppm, cadmium levels of less than 0.002 ppm, and arsenic levels of less than 0.004 ppm. By ‘less than’ it means the amounts are below the detection limits. Very low, indeed!

Q. Can the Licorice in Your Intestinal Rejuvenation Formula Cause High Blood Pressure?

irf-product-includesA. The licorice in Intestinal Rejuvenation Formula is from the powdered root of organically grown licorice. Each serving contains 40 mg. It is highly unlikely that this amount of the whole root could cause blood pressure issues.


Contact Us:

You can reach HPDI by calling 1-800-228-4265, email support(at)IntegratedHealth.com, or visit the retail website: www.IntegratedHealth.com

Health care professionals and retailers can apply for wholesale account, which includes access to the HPDI reseller website: www.HealthProductsDistributors.com




Dr. Hank Liers, PhD 5-MTHF and Folinic Acid folate coenzymeFred Liers PhD 5-MTHF and Folinic Acid folate coenzyme

It is important to know that our scientific knowledge of the B vitamin folate has undergone significant changes in the last 10 years based upon some amazing research studies.

We have come to understand that the biologically active and naturally ocurring folate forms of L-5-methyltetrahydofolate (5-MTHF) and 5-formyltetrahydrofolate (folinic acid) are significantly more effective than folic acid, which is a synthetic oxidized form of folate.

For many years (at least since the 1940s), the only form of folate used in supplements and fortified foods was folic acid. However, a significant body of research has shown that supplemental folic acid may actually accelerate cognitive decline in some older individuals. Folic acid also is being linked to increased risk of colon and rectal cancers, increased risk of childhood asthma born to folic-acid supplemented mothers, and accelerated growth of pre-existing tumors.

Many studies have indicated that a large portion of the population (about 50%) have genetic deficiencies in the enzymes (such as MTHFR) that do not allow the body to properly metabolize folic acid into coenzyme forms needed for proper body function.

Unfortunately, journalists and even many medical professionals haven’t understood that folic acid is not the same as the naturally occurring vitamin folate. Even today, much of the medical mainstream use the terms “folic acid” and “folate” interchangeably. Yet, folic acid is not the same as folate!

The good news is that the folate coenzymes of 5-MTHF and Folinic Acid are now readily available for use in nutritional supplements and are being incorporated into products by knowledgeable companies.


Folate is a water-soluble B vitamin that is naturally present in foods. Folates are  commonly consumed through a diet of green leafy vegetables, sprouts, fruits, brewer’s yeast, animal products such as milk and dairy products, egg yolk, and liver. Formerly known as “folacin,” folate is the generic term for both naturally occurring food folate and folic acid.

spinach folate

Spinach and other green leafy vegetables provide naturally occurring folate.

When consumed, food folates are often hydrolyzed to the monoglutamate form in the gut prior to absorption by active transport across the intestinal mucosa. Passive diffusion also occurs when pharmacological doses of folic acid are consumed.

Before entering the bloodstream, the monoglutamate form is reduced to tetrahydrofolate (THF) and converted to either methyl or formyl forms. However, both of the metabolically active (coenzyme) forms 5-methyl tetrahydrofolate (5-MTHF) and 5-formyl tetrahydrofolate (also known as folinic acid) are found in foods and can enter the cells with no further modification.

Unfortunately folates contained in foods are unstable and susceptible to oxidation; they rapidly lose activity during food processing, manufacturing and storage and have a bioavailability range of 25–50%, depending on the kind of food. Fresh leafy vegetables stored at room temperature may lose up to 70% of their folate activity within three days and a cooking process in water can increase the loss to 95%.

Humans cannot synthesize folate and because of its water soluble nature, the body stores folate to a limited extent. For this reason folate represents a dietary requirement and must be consumed by diet.


Folate deficiency represents one of the most common nutritional deficiencies and may occur when dietary intake is inadequate, when an increased need is not matched by an increased intake (particular physiological conditions such as pregnancy, lactation, child growth), when there is altered absorption/excretion (or losses) and when metabolism or drug use interferes with the ability of the body to use folate.

Several conditions can lead to nutritional folate deficiency. These not only include enzyme defects, malabsorption, digestive system pathology, and liver disease, but also conditions with a high rate of cell turnover such as rapid tissue growth (infants, kids and adolescents), and pregnancy and lactation.

In severe cases deficiency can cause many clinical abnormalities, including macrocytic anemia, cardiovascular diseases, birth neural tube defects (NTDs) and carcinogenesis. Folate deficiency is associated with elevated levels of homocysteine, cerebrovascular and neurological diseases, and mood disorders.


Folate coenzymes are responsible for the following metabolic functions and benefits:

1) Formation of purines and pyrimidines, which in turn are needed for synthesis of the nucleic acids DNA and RNA. This is especially important during fetal development in the first trimester in preventing birth defects, such as neural tube defects.

2) Formation of heme, the iron-containing protein in hemoglobin

3) Interconversion of the 3-carbon amino acid serine from the 2-carbon amino acid glycine

4) Formation of the amino acids tyrosine from phenylalanine and glutamic acid from histidine

5) Formation of the amino acid methionine from homocysteine (Vitamin B12 as methylcobalamin also is needed for this conversion). Elevated levels of homocysteine have been implicated in a wide range of health disorders including atherosclerosis, osteoporosis, Alzheimer’s disease, and depression. In the reconversion of homocysteine to methionine the body uses the methionine to make the important amino acid s-adenosylmethionine (SAMe) which is known to be helpful in cases of depression.

6) Synthesis of choline from ethanolamine

7) Formation and maturation of red and white blood cells

8) Conversion of nicotinamide to N’-methylnicotinamide

Numerous drugs are known to inhibit the body’s ability to utilize folate, including: 1) aspirin, 2) cholesterol lowering drugs, 3) oral birth control pills, 4) antacids, and 5) methotrexate when used for rheumatoid arthritis. When taking these drugs (and many others) it is recommended that you take at least 800 mcg daily of folate, preferably as 5-MTHF and folinic acid.

When taking folate it is recommended that you take adequate amounts of Vitamin B12 as methylcobalamin.


The figure (1.1) shown below provides an overview of how the three forms of folate we will be discussing are metabolized in the cell. Basically the diagram shows that there are two major uses of folate in the body 1) Those dealing with methylation reactions and 2) those dealing with nucleotide biosynthesis, e.g., the production of DNA and RNA.

On the bottom left the diagram shows that 5-MTHF can directly enter the cell and be used for methylation reactions such as the conversion of homocysteine into methionine. On the bottom right the diagram shows that 5-formyl tetrahydrofolate (folinic acid) can directly enter the cell and be used for nucleotide biosynthesis after a few enzymatic conversions.

The top of the diagram shows that folic acid can enter the cell, but must go through a series of enzymatic conversions in order to accomplish what 5-MTHF and folinic acid can accomplish. The box in the lower middle of the diagram indicates where the MTHFR enzyme (see the line with the #5) deficiency can block the metabolism of folic acid.

The diagram shows that all of the important reactions can be accomplished by either 5-MTHF or folinic acid as they can be converted to one another by a series of enzymatic reactions. An important study (see abstract below) has indicated that at least in some cases the presence of a MTHFR enzyme deficiency does not impede the conversion of folinic acid into 5-MTHF.

Folate Metabolism 5-MTHF and Folinic Acid

1.1. Diagram of Folate Metabolism from Vitamin Analysis for the Health & Food Sciences by Ronald R. Eitenmiller and W.O. Lander, Jr.

FOLIC ACID: Once isolated and exposed to air natural folates in food becomes unstable and breaks down, and are generally no longer useful in nutrition. But a small amount of natural folate can be transformed by oxidation (a natural process) into folic acid, a much more stable form with a very long shelf life.

While human and animal cells cannot use the folic acid molecule itself in their normal metabolic processes, human cells (principally the liver) can transform folic acid back into many of its metabolically useful folate forms. That is why folic acid—despite not being found in food—can do so much nutritional good. The best-known example is the prevention of birth defects including spina bifida, cleft lip, and cleft palate.

As we age, however, our bodies become increasingly slower at transforming folic acid into usefully metabolized folates. That’s probably the reason scientists are finding that folic acid (not folate) is associated with cognitive decline in the elderly. Some of these studies have shown significantly elevated levels of unmetabolized (and therefore not useful) folic acid building up in the bloodstreams of supplemented older individuals.

In addition to worsening folic acid metabolism with age, there are also a significant number (as high as 45 percent or more in some populations) of survivable human genetic defects of folate metabolism (MTHFR deficiency) which make it more difficult or, in some circumstances, impossible for sufferers to make metabolic use of folic acid.

We believe it is time to make folic acid supplements a part of history, and use only forms of naturally occurring folate when we use supplements. Although my company produces a liquid folic acid supplement that has been especially useful for some pregnant women who are experiencing gum problems, we have been incorporating the coenzyme form Folinic Acid into supplements for over 10 years, and recently introduced the metabolically active form L-5-MTHF.

A small amount of folic acid (100–200 micrograms, the amount found in many multiple vitamins at present) is not likely to be a major problem for most people. However, more taken daily for years just might raise your long-term risk of colorectal cancer, cognitive decline, or other symptoms of elevated levels of homocysteine. If higher amounts are unavoidable (for example, until all prenatal vitamins switch from folic acid to folate), taking additional folate as 5-MTHF and Folinic Acid will very likely offset the folic acid still found in the multiple. In this regard, I have over the last five years eliminated folic acid from all of the multivitamins and B-Complex vitamins that we now make available.

FOLINIC ACID: Also known as 5-formyl tetrahydrofolate, it is one active form in a group of vitamins known as folates. In contrast to folic acid, a synthetic form of folate, folinic acid is one of the forms of folate found naturally in foods. In the body folinic acid may be converted into any of the other active forms of folate.

Compared to folic acid, folinic acid is expensive costing about 100 times more. However, the fact that the body only requires small amounts (less than one mg) means that one can obtain a two month supply of folinic acid for less than $10.

Folinic acid has been available as a supplement for more than 10 years and as such has been the form most used as a replacement for folic acid.

5-MTHF: Also known as L-5-methyl tetrahydrofolate, it has been difficult to obtain until recently. An Italian company has made a patented form available (Quatrefolic®) that is combined with a vegetarian glucosamine. This form is particularly stable and highly bioavailable.

5-MTHF costs about 400 times more than folic acid. However, because the body requires less than one milligram (1 mg) on a daily basis, a person can buy a two-month supply for about $20.

5-MTHF is now readily available on the market, thereby making it possible to purchase at reasonable prices both coenzyme forms of folate.


As we noted, the importance of natural coenzyme forms of folate is highlighted by the large number of people who cannot convert folic acid to folate usable in the body because they lack the enzymes necessary to make this conversion due to genetics, aging, or faulty metabolism.

For the nearly half of all persons (in some populations) having the functional variation (i.e., mutation) on the MTHFR gene resulting in MTHFR deficiency makes them unable to convert folic acid to a folate form like 5-MTHF that usable by cells. This not only means that their bodies have problems processing B-group vitamins, but also can mean they suffer significant deficiencies (as well as elevated blood folate).

Folate deficiencies can lead to anxiety and panic attacks. Moreover, they can lead to other mood issues, miscarriages, as well as vascular conditions. Recall that elevated levels of homocysteine are associated with folate deficiency.

Another area of interest is research indicating that up to 20% of individuals who carry the MTHFR gene experience migraine headaches.

The effectiveness of natural folates for migraine headaches in persons with MTHFR deficiency is becoming more widely known. Here is a TEDx talk by Prof. Lyn Griffiths from the Griffith Health Institute in Australia showing her work with MTHFR deficiency and migraine (https://www.youtube.com/watch?v=BOgbmF0jYd4). This aspect of her work is highlighted near the end of her talk.

The use of natural folates to help individuals suffering from migraine headache is an area holding great promise.


Folic acid is not the same as folate. Folic acid can present problems in persons lacking the enzymes necessary to convert it into usable forms. Folic acid can also build up in the body in potentially toxic ways.

Supplementing with naturally occurring coenzyme folates, such as 5-MTHF and folinic acid makes sense given advances in our understanding of how the body utilizes dietary folates.

HPDI incorporates natural folate forms into all of its multivitamins and folate products.



Conversion of 5-formyltetrahydrofolic acid to 5-methyltetrahydrofolic acid is unimpaired in folate-adequate persons homozygous for the C677T mutation in the methylenetetrahydrofolate reductase gene.

From: http://www.ncbi.nlm.nih.gov/pubmed/10958818


Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolic acid (5-CH(3)-H(4) folic acid), the methyl donor for the formation of methionine from homocysteine. A common C677T transition in the MTHFR gene results in a variant with a lower specific activity and a greater sensitivity to heat than the normal enzyme, as measured in vitro. This study was undertaken to determine the capacity of homozygotes for the MTHFR C677T transition to convert 5-formyltetrahydrofolic acid (5-HCO-H(4) folic acid) to 5-CH(3)-H(4) folic acid, a process that requires the action of MTHFR. Six subjects homozygous for the C677T transition (T/T) and 6 subjects with wild-type MTHFR (C/C) were given a 5-mg oral dose of (6R:,S:)-5-HCO-H(4) folic acid. Plasma and urine were analyzed for 5-CH(3)-H(4) folic acid concentrations using affinity/HPLC coupled with fluorescence or UV detection. The mean areas under the curves created by the rise and fall of plasma 5-CH(3)-H(4) folic acid after the oral dose did not differ between the two genotypes, 424.5 +/- 140.3 (T/T) vs. 424.1+/- 202.4 h.nmol/L (C/C). There also was no significant difference in the mean cumulative 7-h urinary excretion of 5-CH(3)-H(4) folic acid between the T/T (2.5 +/- 1.4 micromol) and C/C (1.9 +/- 1.0 micromol) genotypes. Under the conditions employed, the conversion of oral 5-HCO-H(4) folic acid to 5-CH(3)-H(4) folic acid is not impaired in persons with the T/T MTHFR genotype. Possible reasons for these findings are discussed.


Folate, folic acid and 5-methyltetrahydrofolate are not the same thing.

From: http://www.ncbi.nlm.nih.gov/pubmed/24494987


1. Folate, an essential micronutrient, is a critical cofactor in one-carbon metabolism. Mammals cannot synthesize folate and depend on supplementation to maintain normal levels. Low folate status may be caused by low dietary intake, poor absorption of ingested folate and alteration of folate metabolism due to genetic defects or drug interactions. 2. Folate deficiency has been linked with an increased risk of neural tube defects, cardiovascular disease, cancer and cognitive dysfunction. Most countries have established recommended intakes of folate through folic acid supplements or fortified foods. External supplementation of folate may occur as folic acid, folinic acid or 5-methyltetrahydrofolate (5-MTHF). 3. Naturally occurring 5-MTHF has important advantages over synthetic folic acid – it is well absorbed even when gastrointestinal pH is altered and its bioavailability is not affected by metabolic defects. Using 5-MTHF instead of folic acid reduces the potential for masking haematological symptoms of vitamin B12 deficiency, reduces interactions with drugs that inhibit dihydrofolate reductase and overcomes metabolic defects caused by methylenetetrahydrofolate reductase polymorphism. Use of 5-MTHF also prevents the potential negative effects of unconverted folic acid in the peripheral circulation. 4. We review the evidence for the use of 5-MTHF in preventing folate deficiency.

Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?


Women have higher requirements for folate during pregnancy. An optimal folate status must be achieved before conception and in the first trimester when the neural tube closes. Low maternal folate status is causally related to neural tube defects (NTDs). Many NTDs can be prevented by increasing maternal folate intake in the preconceptional period. Dietary folate is protective, but recommending increasing folate intake is ineffective on a population level particularly during periods of high demands. This is because the recommendations are often not followed or because the bioavailability of food folate is variable. Supplemental folate [folic acid (FA) or 5-methyltetrahydrofolate (5-methylTHF)] can effectively increase folate concentrations to the level that is considered to be protective. FA is a synthetic compound that has no biological functions unless it is reduced to dihydrofolate and tetrahydrofolate. Unmetabolized FA appears in the circulation at doses of >200 μg. Individuals show wide variations in their ability to reduce FA. Carriers of certain polymorphisms in genes related to folate metabolism or absorption can better benefit from 5-methylTHF instead of FA. 5-MethylTHF [also known as (6S)-5-methylTHF] is the predominant natural form that is readily available for transport and metabolism. In contrast to FA, 5-methylTHF has no tolerable upper intake level and does not mask vitamin B12 deficiency. Supplementation of the natural form, 5-methylTHF, is a better alternative to supplementation of FA, especially in countries not applying a fortification program. Supplemental 5-methylTHF can effectively improve folate biomarkers in young women in early pregnancy in order to prevent NTDs.