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D-RIBOSE: ENERGIZING SMART SUGAR

Fred Liers PhD riboseAvoiding excess dietary sugars is one of the healthiest things. But there is one sugar that really is good for you. That sugar is D-ribose.

In fact, D-ribose is so healthy for you, it may be the one sugar you won’t want to live without. A little background to this amazing sugar.

D-ribose is a 5-carbon monosaccharide occurring naturally in living cells. D-ribose importantly forms the carbohydrate parts of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). That means d-ribose is the sugar essential for the biological function of all living creatures, including humans.

Supplemental D-ribose is associated with many benefits. These benefits include greater energy, less fatigue, and faster muscle recovery. These benefits relate to the capacities of D-ribose as a total body energizer because it boosts energy production (as ATP) in the body.

For individuals suffering low energy levels associated with chronic fatigue syndrome (CFS), low energy levels, and other problems related to low energy (ATP) production, D-ribose can mean a significantly higher level of energy. In cases of extremely low energy, it can mean the capacity to function more normally.

ribose energy woman power health

D-ribose energizes every cell in our bodies.

Athletes and bodybuilders were among the earliest to recognize D-ribose for purposes of improving performance and recovery times. D-Ribose also exerts anti-anxiety, stress reduction, and potential anti-depressant properties. There is additional evidence suggesting that supraphysiological amounts of ribose may have cardioprotective effects, especially for the ischemic heart.

Supplemental D-ribose usually comes in the form of a sweet, crystalline, water-soluble powder. It is also available in capsules or tablets, including chewable tablets.

Humans synthesize d-ribose from foods, including glucose and various dietary sugars. But there are benefits to supplemental D-ribose. One of the major reasons is the important role of D-ribose in the production of energy (ATP) in human cells.

D-RIBOSE BENEFITS

• GREATER ENERGY (ATP) PRODUCTION

• FASTER RECOVERY

• REDUCED FATIGUE

• IMPROVES ATHLETIC PERFORMANCE

• SUPPORTS MITOCHONDRIAL FUNCTION

• AIDS CHRONIC FATIGUE AND FIBROMYALGIA

• SUSTAINS CARDIAC AND SKELETAL MUSCLE

• BETTERS PHYSIOLOGICAL FUNCTION UNDER ANAEROBIC CONDITIONS

• SUPPORTS LONGEVITY OF BLOOD CELLS

• ANTI-ANXIETY EFFECTS

• STRESS REDUCTION

ribose sugar natural heart energy ATP RNA

D-ribose is heart healthy unlike most dietary sugars (e.g., sucrose).

RIBOSE FOR ENERGY (ATP) PRODUCTION

The body uses D-ribose to generate adenosine triphosphate (ATP).  ATP provides energy for all bodily movements and every chemical reaction in cells. ATP is the source of all energy in the body and it’s constantly broken down and recreated due to the processes of life.

The adenine portion of ATP consists of one molecule of adenine and ribose (i.e., five-carbon sugar). The triphosphate portion of ATP consists of three phosphate molecules. When a phosphate breaks off from ATP, then energy is released. The compound then becomes adenosine diphosphate (ADP), which consists of adenosine and two phosphate molecules. When another phosphate molecule breaks off, it becomes adenosine monophosphate (AMP).

It is well established that ratios of ATP, ADP, and AMP are essential for regulating energy in cells. Under extreme physiological stress (e.g., high-intensity exercise), our cells cannot recreate ATP rapidly enough to supply cells with required energy. Concentrations of ADP and AMP rise causing a reduction in cellular energy. When the body’s rate of ATP use continues exceeding the rate at which it can be generated, cells “lose” nucleotides in order to restore the ratio between ATP, ADP, and AMP.

During anaerobic metabolism, AMP levels can rise within cells, thereby disturbing the ratios of ATP to ADP and AMP. The body can reduce AMP concentrations by degrading AMP to simpler end products resulting in a significant decrease in the adenine nucleotide pool. Under extreme conditions (e.g., prolonged high-intensity exercise or the diminished blood flow to tissues witnessed in ischemia), the adenine nucleotide pool may decrease by 30–50%. These effects can significantly compromise physical performance.

Here is where D-ribose supplementation works to support energy production. Supplemental D-ribose allows the body to bypass relatively slow conversion steps required for recreating the adenosine nucleotide providing critical material for ATP production. That is, D-ribose can increase the speed of nucleotide replacement. This has implications not only for sports performance, but also for general health. D-ribose is especially useful in situations where greater energy may be required, as in low energy, chronic fatigue, fibromyalgia, or combating the effects of aging.

D-RIBOSE RATE-LIMITING SUGAR FOR NUCLEOTIDE SYNTHESIS

One of the most important aspects of D-ribose for health relates to the fact that it is the rate-limiting compound that regulates the activity of the purine nucleotide pathway of adenine nucleotide metabolism. As such, ribose plays a central role not only in the synthesis of ATP, but also of coenzyme-A, flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NAD), DNA, RNA, and other important cellular constituents.

In fact, D-ribose is the only known compound the body can use for performing this critical metabolic function. Specifically, ribose administration bypasses the slow and rate-limited pentose phosphate pathway to stimulate adenine nucleotide synthesis and salvage in vivo. In addition, it has been shown that de novo adenine nucleotide synthesis in skeletal muscle is rate limited by the availability of ribose.

Specifically, human muscle cells (e.g., heart and skeletal muscle cells) do not rapidly replace lost nucleotides because of the lack of two rate-limiting enzymes in the pentose phosphate pathway metabolizing glucose to ribose-5-phosphate. Ribose itself forms 5-phosphoribosyl-1-pyrophosphate, a rate-limiting compound in nucleotide synthesis. As noted, supplemental D-ribose allow the body to bypass the rate-limited steps of the pentose phosphate pathway, thereby accelerating nucleotide synthesis (and salvage).

STOPPING THE VICIOUS CYCLE OF ENERGY DEPLETION

It should not take a genius to figure out that when energy production is optimized, overall health will improve. Yet, the same principle also applies in reverse. That is, there are many instances in which low energy levels can fuel lower energy levels. For example, when illness, stressors, or other factors deplete large amounts of the body’s supply of energy, they can gradually (or not so gradually) lessen the body’s capacity to produce more by overtaxing the energy production system.

This cascade of reduced energy production can become a vicious cycle in which there are few reserves left to support the body’s need for greater energy. D-Ribose is one of the only nutrients that can reverse the downward spiral in ATP production when demands exceed supply. By feeding the body’s own system for producing energy, and thereby supplying the raw material required to produce it, supplemental D-ribose can helps break the cycle of low energy levels.

fatigue ribose natural sugar energy atp cells

Chronic low energy? D-ribose is required for creating energy for all biological functions.

A ROLE FOR SUPPLEMENTAL D-RIBOSE

To recap the importance of supplemental D-ribose: D-ribose increases the rate at which ATP is generated. This improves exercise performance and allows for faster muscle growth. All this is possible because supplemental ribose helps the body bypass the conversion steps needed to create or re-create adenosine nucleotides.

Because replacing adenine nucleotides normally requires a certain amount of time, providing the body with D-ribose supplementally via diet can reduce rates of healing and repair in muscle cells. That is, supplemental D-ribose can increase the speed at which adenosine nucleotides are replaced by providing raw material for the creation of more ATP. That is how D-ribose improves athletic performance and supports optimal energy production, as well as optimal muscle health.

The significance of the science behind ATP production is that almost everyone can benefit from supplemental D-ribose. Whether you are an athlete requiring rapid repletion of energy, a person suffering from low energy levels or chronic fatigue, or anyone who wishes to improve energy production supporting optimal health.

ribose energizes beautiful athletic girl with colorful balloons jumping on the beach

Fatigued to fantastic: a plentiful supply of D-ribose helps ensure an abundance of energy.

REJUVENATE! SUPERFOODS INCLUDE D-RIBOSE

We at HPDI have focused our efforts on formulating the most effective nutritional supplements and superfoods. When Dr. Hank Liers formulated our original high-RNA Rejuvenate! superfood, he put D-ribose into it. In fact, all of our Rejuvenate! superfoods provide significant amounts of D-ribose.

Rejuvenate! (original greens) provides 1,500 mg D-ribose per serving (one small scoop). Rejuvenate! PLUS provides 1,800 mg per serving (two scoops). Rejuvenate! Berries & Herbs provides 2,000 mg per serving (two scoops).

ribose energy dietary nucleic acids rejuvenate superfoods

All Rejuvenate! superfoods provide high levels of D-Ribose.

A major reason HPDI includes D-ribose in its superfoods–and perhaps the most obvious one–is simply that we formulate unique, high-RNA superfoods to support optimal energy production in the body. D-ribose supports that goal by various means.

D-ribose is the rate-limiting sugar for the uptake and assimilation of dietary nucleic acids (RNA, DNA, nucleotides, and nucleosides). This is because D-ribose is actually the sugar backbone of these nutrients. As such, the body requires D-ribose in order to utilize and create (or recreate) dietary nucleic acids.

For example, nucleotides are the molecular building blocks of DNA and RNA. They are chemical compounds consisting of a heterocyclic base, a 5-carbon sugar (ribose or deoxyribose) and at least one phosphate group. They are the monomers of nucleic acids, and 3 or more can bond together to form a nucleic acid.

Nucleosides are glycosylamines consisting of a base (or nucleobase) to a ribose (or deoxyribose) ring. Some nucleosides are cytidine, adenosine, guanosine, and inosine. When nucleosides are phosphorylated in cells, they produce nucleotides (see above).

Thus, D-ribose plays important roles as an essential part of nucleic acids, nucleotides, and nucleosides; in the production of energy (as ATP); and the synthesis and salvage of nucleotides in the body.

Rejuvenate! superfoods are formulated to provide high levels of nucleic acids. D-ribose helps the body optimize its use of nucleic acids and their constituent components. Having D-ribose in our superfoods not only supports energy production directly, but also allows maximum use of the dietary RNA they are formulated to provide.

Rejuvenate! superfoods provide nutrients that boost energy levels significantly and consistently for optimal health, healing, and wellness. The inclusion of D-ribose importantly supports the powerful nucleic acid nutrition these superfoods offer, as well as supplements the body’s intake and synthesis of D-ribose.

ribose energy rejuvenate plus (500g) RNA nucleic acids doctor hank liers original

REJUVENATE! PLUS provides 1,800 mg of D-ribose per serving.

SUMMARY

D-Ribose of one of the most important natural sugars for life and health. It is one of the few nutrients that can boost energy levels naturally. When taken with other important biological nutrients, including dietary RNA, DNA, nucleotides, and nucleosides, D-ribose is truly a nutritional powerhouse that can support good health and the energy levels required to live life to its fullest. We believe the best way to obtain supplemental D-ribose is to consume Rejuvenate! superfoods.

SOURCES & RESOURCES

REJUVENATE! SUPERFOODS

REJUVENATE! PLUS

REJUVENATE! BERRIES & HERBS

REJUVENATE! ORIGINAL (GREENS)

REJUVENATE! COMPARISON GUIDE

HPDI BLOG ARTICLES

GET RESULTS WITH REJUVENATE SUPERFOODS

9 THINGS TO KNOW ABOUT REJUVENATE! SUPERFOODS

DIETARY RNA FOR ATHLETIC PERFORMANCE

TECHNICAL INFORMATION

Pentose-Phosphate Pathway: Elsevier’s Review of Biochemistry

From Fatigued to Fantastic (excerpt) by Jacob Teitelbaum, MD

D-Ribose technical information (Vista Chemicals)

Enhancing Cardiac Energy with Ribose (LEF)

SCIENTIFIC STUDIES

The Use of D-Ribose in Chronic fatigue syndrome and fibromyalgia (J Altern Complement Med.)

D-Ribose Aids Advanced Ischemic Heart Failure Patients (Int J Cardiol.)

D-Ribose, a Metabolic Substrate for Congestive Heart Failure (Prog Cardiovasc Nurs.)

D-Ribose as a Supplement for Cardiac Energy Metabolism (J Cardiovasc Pharmacol Ther.)

Ribose Accelerates the Repletion of the ATP Pool During Recovery from Reversible Ischemia of the Rat Myocardium (J Mol Cell Cardiol.)

Significance of the 5-phosphoribosyl-1-pyrophosphate pool for cardiac purine and pyrimidine nucleotide synthesis: studies with ribose, adenine, inosine, and orotic acid in rats (Cardiovasc Drugs Ther.)

Stimulation of Myocardial Adenine Nucleotide Biosynthesis by Pentoses and Pentitols (Pflugers Arch.)

The Role of Ribose on Oxidative Stress During Hypoxic Exercise (J. Med. Food)

D-Ribose Benefits Restless Legs Syndrome (J Altern Complement Med.)

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AMARANTH REJUVENATE POWER SMOOTHIE & JUICE RECIPES

Stefanie Lischer-Liers LAc amaranth rejuvenate power smoothie

Summer is in full swing and so are many native plants that flourish with the Sonoran desert monsoon rains. Our yard is full of wild amaranth and purslane, two amazingly nutritious “weeds.”

With the desert in full bloom, it is relatively easy to consume local foods in season just by heading out the back door.

I’ve been making a smoothie every morning with a large handful of wild amaranth leaves. The purslane is so tasty that I’ve been grazing on it directly from the yard. But is is also delicious in smoothies, salads, and stir-fries, or put into foods like quesadillas or sandwiches.

Here is the recipe for my Amaranth Rejuvenate! Power Smoothie. I also include other recipe ideas for juicing amaranth, purslane, and prickly pear fruits.

AMARANTH REJUVENATE!™ POWER SMOOTHIE

INGREDIENTS

• 1 frozen or fresh Fig*
• Several chunks frozen Mango*
• Frozen or fresh Blueberries*
• 1 Cup plain organic Yogurt (Greek-style works nicely)
• 1–2 Scoops REJUVENATE! PLUS / Berries & Herbs / Original Greens
• 1 Teaspoon raw organic Cacao powder (optional)
• Organic rice/almond/hemp milk add to create to desired consistency
• 1–2 Handfuls wild Amaranth leaves, Purslane or other fresh greens like spinach, kale, etc.
• Sprig of fresh Mint (optional)

(*any frozen organic fruit can be substituted)

DIRECTIONS

Place in a large mason jar and blend with hand blender. Or use a regular blender. Serve and enjoy!!

smoothie rejuvenate amaranth

Step 1. Assemble ingredients for Amaranth Rejuvenate Power Smoothie.

amaranth rejuvenate power smoothie superfoods

Step 2. Place ingredients in blender or container for stick blender.

rejuvenate amaranth power smoothie drink

Step 3. Blend and enjoy!!

AMARANTH IS A NUTRITION POWERHOUSE

You may never have eaten amaranth, but chances are good it grows near you. There are more than 60 species of amaranth. Not only does it grow in temperate and tropical regions around the world, but also is cultivated widely as a leaf vegetable and for its seeds. The leaves, stems, and roots are consumed in East, Souththeast, and South Asia (including China and India), the Mediterranean, Africa, and the Americas.

The word amaranth derives from Greek “amarantos” meaning “unfading.” The Greek word in turn derives from an ancient Indian Sanskrit word meaning “immortal immortal.” That’s an illustrious etymological significance for a plant our culture often regards as a weed.

Amaranth historically holds importance as a staple food among Native American cultures. Known to the Aztecs as “huauhtli,” it constituted perhaps 80% of caloric consumption before the arrival of the Spanish in Mesoamerica.

Native American cultures consumed amaranth greens, but primarily used the seeds as a grain. Amaranth seed is considered a pseudograin (like quinoa) due to its flavor and cooking properties. It is gluten free, high in protein, and easy to prepare.

The Aztecs used amaranth extensively in their religious ceremonies, especially those dedicated to their sun god Huitzilopochtli. During ritual ceremonies, the Aztecs would create a statue of him made of amaranth grain. Pieces of this statue were distributed among the celebrants.

Amaranth summer smoothie recipe rejuvenate superfoods

Wild amaranth is available for the picking during summer months.

Amaranth smoothie rejuvenate superfoods purslane

Amaranth leaves are ideal for smoothies, salads, stir fries, or eaten directly from the plant.

The Spanish outlawed cultivation of amaranth (and chia seeds) thereby removing an important part of the Aztec diet. Notably, amaranth seed is high in lysine, an amino acid which is low in corn (another Aztec staple food) and therefore helped balance their diet.

Aztecs didn’t drink smoothies or juice greens. Yet, amaranth is back in cultivation in the Americas, and grows wild in yards (like ours) everywhere. Take a closer look at the weeds in your yard. You might just find breakfast, dinner, or a nutritious smoothie ingredient!!

PURSLANE

Purslane is a succulent that is tender, juicy, and slightly tangy or tart. There is plenty of it growing in our yard. In fact, it grows just about anywhere from meadows, forests and deserts to urban lots and sidewalk cracks. Consider yourself fortunate if this wild edible grows in your yard or neighborhood because its nutritional content is second to none.

purslane

Nutritious purslane is often considered a superfood.

Purslane is a rich source of antioxidants, essential fatty acids, dietary fiber, as well as vitamins and minerals. It provides more nutrients than almost any of the greens we typically consume today. Vitamins it contains include vitamin A, B1, B2, B3, B6, C, and E. Purslane also offers calcium, magnesium, iron, copper, manganese, phosphorous, and especially potassium.

Purslane not only provides a wide range of nutrients, but offers them in abundance. It is particularly high in vitamin E and contains six times more beta-carotene than spinach. The levels of essential fatty acids it provides are the highest among all leafy green vegetables.

Purslane makes an excellent addition to your smoothies and juices. It is also superb in salads, soups, or steamed.

PRICKLY PEAR FRUITS

Another desert monsoon delectable is the prickly pear fruit. Our family went out this weekend and harvested the ripest fruits and juiced them. The juice is sweet enough to drink by itself or even watered down a bit. (Note: use tongs to pull fruits from cactus paddles to avoid sharp spines and tiny glochids on the fruit surfaces.)

prickly pear fruit amaranth leaf juice smoothie rejuvenate superfoods

Ripe prickly pear fruits produce delicious juice for smoothies and power-up drinks.

I juiced the prickly pear fruit and amaranth plant separately, and then mixed them together. Drinking that juice is a real power boost!

The Hurom juicer (single augur) does much better with prickly pear fruit than the twin gear Green Star, which became quickly jammed with seeds.

Some people might like to add pineapple juice or lemon juice and maple syrup to concentrated amaranth juice. Note that for juicing purposes, the entire amaranth plant can be juiced (leaves, stalks and all).

Add a scoop of Rejuvenate! (original) superfood plus a dash of lemon juice and maple syrup to the amaranth and prickly pear juice for a real lift to your day!

prickly pear fruits smoothie amaranth juice rejuvenate superfoods

Prickly pear fruits ready for juicing.

PRICKLY PEAR REJUVENATE DRINK

INGREDIENTS

• 6–10 ounces Prickly Pear fruit juice (fresh is best)
• 1 scoops REJUVENATE! (Original Greens) superfood
• 1–2 ounces Amaranth juice (or to taste) (optional)
• Organic Lemon juice or Pineapple juice (to taste) (optional)
• Maple syrup (to taste) (optional) (grade B organic best)

DIRECTIONS

Juice the prickly pear fruits and amaranth leaves (separately or together). Mix together with Rejuvenate! original (or the Rejuvenate! superfood of your choice). Add lemon or pineapple juice and/or grade B organic maple syrup. Enjoy!

amaranth prickly pear juice smoothie rejuvenate superfoods

Amaranth and prickly pear juices provide a rainbow of antioxidant phytochemicals.

PRICKLY PEAR LEMONADE

We enjoy a delicious variant of the Prickly Pear Rejuvenate Drink we call “prickly pear lemonade.” Prickly Pear Lemonade is very refreshing and hydrating on warm summer days. It is delicious with maple syrup, chlorella, or Rejuvenate! superfoods.

INGREDIENTS

• 2 Ounces Lemon juice (fresh squeezed or bottled) (organic)
• 2–4 Ounces Prickly Pear fruit juice
• 6–8 Ounces fresh water
Rejuvenate! Superfoods (optional)
• Maple syrup (to taste) (grade B organic) (optional)
• Chia seeds (whole or ground) (optional)
• Ice (optional)
• Mint sprigs (optional)

(Recipe makes 10–14 ounces. Adjust ingredients to taste or when making larger quantities.)

DIRECTIONS

Fill glass or pitcher with fresh water. Add prickly pear juice, lemon juice, and maple syrup. Add Rejuvenate! superfoods, chlorella, chia seeds, mint sprigs, and/or ice, as desired.

prickly pear lemonade amaranth smoothie rejuvenate

Prickly pear lemonade refreshes, hydrates, and tastes great!!

The rains of summer bring a burst of life into the desert, including a wide variety of edible plants and their fruits. We are blessed that our yard and surrounding area provide such an abundance of fresh greens and prickly pear fruits. We will consume them in our smoothies and juices well into the fall.

RESOURCES

Nature’s Garden: A Guide to Identifying, Harvesting, and Preparing Wild Edible Plants

The Forager’s Harvest: A Guide to Identifying, Harvesting, and Preparing Wild Edible Plants

Edible Wild Plants: Wild Foods From Dirt To Plate

Backyard Foraging: 65 Familiar Plants You Didn’t Know You Could Eat

Free Food and Medicine Worldwide Edible Plant Guide

Why is Wild Purslane a Prized Superfood?

REJUVENATE! SUPERFOODS

Rejuvenate! PLUS

Rejuvenate! (original greens)

Rejuvenate! Berries & Herbs

Rejuvenate! Superfoods: Which One is Right for Me?

PHOTO GALLERY

amaranth rejuvenate power smoothie blender

A Kitchen Aid hand blender makes smoothies easy.

hurom juicer rejuvenate amaranth smoothie prickly pear juice purslane greens superfoods

The Hurom juicer is perfect for juicing greens and prickly pear fruits.

prickly pear amaranth juice smoothie power drinks foraging rejuvenate superfoods

Prickly pear fruits ripe for picking.

chickens wild amaranth greens foraging

Chickens love eating wild amaranth as much as people do.

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ULTIMATE PROTECTOR INGREDIENTS – BROCCOLI AND BROCCOLI SPROUTS

Dr. Hank Liers, PhD biography about us HPDI integratedhealth formulator founder CEO scientist physicistUltimate Protector contains broccoli and broccoli sprouts powder, 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 ingredient “broccoli and broccoli sprouts powder,” which is a component of VitaVeggie from Futureceuticals.

VitaVeggie® is an all-vegetable, high-antioxidant (ORAC) capacity blend rich in phenolics from vegetable concentrates, as well as fully intact vegetable phytochemicals from freeze-dried vegetable powders. VitaVeggie combines the nutrients and antioxidants of broccoli, broccoli sprouts, tomatoes, spinach, kale, carrots, brussels sprouts, and onion.

Broccoli Sprouts ultimate protector nrf2

Broccoli Sprouts

This robust vegetable powder is also rich in glucosinolates and sulphoraphane, compounds commonly found in cruciferious vegetables that research suggests contribute to healthy internal antioxidant status by stimulating the body’s endogenous (internal) antioxidant system. VitaVeggie is standardized to minimum levels of 2000 ppm glucosinolates and 1000 ppm sulphoraphane.

SULFORAPHANE

In 1992 a team of Johns Hopkins University scientists isolated a cancer-fighting phytochemical in broccoli called glucoraphanin, which is the glucosinolate precursor of sulforaphane.

When chewed, broccoli releases glucoraphanin and myrosinase, an enzyme found in another part of the plant cell, which work together to produce sulforaphane, which in turn activates a transcription factor (Nrf2) in the cell. After activation, Nrf2 then translocates to the nucleus of the cell, where it aligns itself with the antioxidant response element (ARE) in the promoter region of target genes.

The target genes are associated with processes which assist in regulating cellular defenses. Such cytoprotective genes include that for glutathione. Around 200 genes have been well-characterized, and as many as 1700 may be related to this aspect of cellular defense. The 1992 study was followed by the discovery in 1997 that glucoraphanin is found in higher concentrations in three- to four-day-old broccoli sprouts, at least 20 times the concentration of full-grown broccoli.

STUDIES DEMONSTRATING THE BENEFITS OF BROCCOLI AND BROCCOLI SPROUTS

Implications of Cancer Stem Cell Theory for Cancer Chemoprevention
by Natural Dietary Compounds

Abstract

The emergence of cancer stem cell theory has profound implications for cancer chemoprevention and therapy. Cancer stem cells give rise to the tumor bulk through continuous self-renewal and differentiation. Understanding the mechanisms that regulate self-renewal is of greatest importance for discovery of anti-cancer drugs targeting cancer stem cells. Naturally occurring dietary compounds have received increasing attention in cancer chemoprevention. The anti-cancer effects of many dietary components have been reported for both in vitro and in vivo studies. Recently, a number of studies have found that several dietary compounds can directly or indirectly affect cancer stem cell self-renewal pathways. Herein we review the current knowledge of most common natural dietary compounds for their impact on self-renewal pathways and potential effect against cancer stem cells. Three pathways (Wnt/β-catenin, Hedgehog, and Notch) are summarized for their functions in self-renewal of cancer stem cells. The dietary compounds, including curcumin, sulforaphane, soy isoflavone, epigallocatechin-3-gallate, resveratrol, lycopene, piperine, and vitamin D3, are discussed for their direct or indirect effect on these self-renewal pathways. Curcumin and piperine have been demonstrated to target breast cancer stem cells. Sulforaphane has been reported to inhibit pancreatic tumor initiating cells and breast cancer stem cells. These studies provide a basis for preclinical and clinical evaluation of dietary compounds for chemoprevention of cancer stem cells. This may enable us to discover more preventive strategies for cancer management by reducing cancer resistance and recurrence and improving patient survival.

Targeting cancer stem cells with sulforaphane, a dietary component from broccoli and broccoli sprouts.

Abstract

Many studies have supported the protective effects of broccoli and broccoli sprouts against cancer. The chemopreventive properties of sulforaphane, which is derived from the principal glucosinolate of broccoli and broccoli sprouts, have been extensively studied. Recent research into the effects of sulforaphane on cancer stem cells (CSCs) has drawn lots of interest. CSCs are suggested to be responsible for initiating and maintaining cancer, and to contribute to recurrence and drug resistance. A number of studies have indicated that sulforaphane may target CSCs in different types of cancer through modulation of NF-κB, SHH, epithelial-mesenchymal transition and Wnt/β-catenin pathways. Combination therapy with sulforaphane and chemotherapy in preclinical settings has shown promising results. In this article, we focus on the effects of sulforaphane on CSCs and self-renewal pathways, as well as giving a brief review of recent human studies using broccoli sprout preparations.

Sulforaphane, a dietary component of broccoli/broccoli sprouts,
inhibits breast cancer stem cells.

Abstract

PURPOSE:

The existence of cancer stem cells (CSCs) in breast cancer has profound implications for cancer prevention. In this study, we evaluated sulforaphane, a natural compound derived from broccoli/broccoli sprouts, for its efficacy to inhibit breast CSCs and its potential mechanism.

EXPERIMENTAL DESIGN:

Broccoli nrf2 activator ultimate protector ingredient ARE

Broccoli

Aldefluor assay and mammosphere formation assay were used to evaluate the effect of sulforaphane on breast CSCs in vitro. A nonobese diabetic/severe combined immunodeficient xenograft model was used to determine whether sulforaphane could target breast CSCs in vivo, as assessed by Aldefluor assay, and tumor growth upon cell reimplantation in secondary mice. The potential mechanism was investigated using Western blotting analysis and beta-catenin reporter assay.

RESULTS:

Sulforaphane (1-5 micromol/L) decreased aldehyde dehydrogenase-positive cell population by 65% to 80% in human breast cancer cells (P < 0.01) and reduced the size and number of primary mammospheres by 8- to 125-fold and 45% to 75% (P < 0.01), respectively. Daily injection with 50 mg/kg sulforaphane for 2 weeks reduced aldehyde dehydrogenase-positive cells by >50% in nonobese diabetic/severe combined immunodeficient xenograft tumors (P = 0.003). Sulforaphane eliminated breast CSCs in vivo, thereby abrogating tumor growth after the reimplantation of primary tumor cells into the secondary mice (P < 0.01). Western blotting analysis and beta-catenin reporter assay showed that sulforaphane downregulated the Wnt/beta-catenin self-renewal pathway.

CONCLUSIONS:

Sulforaphane inhibits breast CSCs and downregulates the Wnt/beta-catenin self-renewal pathway. These findings support the use of sulforaphane for the chemoprevention of breast cancer stem cells and warrant further clinical evaluation.

 

Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans.

Abstract

The isothiocyanate sulforaphane [SF; 1-isothiocyanato-4(R)-methylsulfinylbutane] is abundant in broccoli sprouts in the form of its glucosinolate precursor (glucoraphanin). SF is powerfully bactericidal against Helicobacter pylori infections, which are strongly associated with the worldwide pandemic of gastric cancer. Oral treatment with SF-rich broccoli sprouts of C57BL/6 female mice infected with H. pylori Sydney strain 1 and maintained on a high-salt (7.5% NaCl) diet reduced gastric bacterial colonization, attenuated mucosal expression of tumor necrosis factor-alpha and interleukin-1beta, mitigated corpus inflammation, and prevented expression of high salt-induced gastric corpus atrophy. This therapeutic effect was not observed in mice in which the nrf2 gene was deleted, strongly implicating the important role of Nrf2-dependent antioxidant and anti-inflammatory proteins in SF-dependent protection. Forty-eight H. pylori-infected patients were randomly assigned to feeding of broccoli sprouts (70 g/d; containing 420 micromol of SF precursor) for 8 weeks or to consumption of an equal weight of alfalfa sprouts (not containing SF) as placebo. Intervention with broccoli sprouts, but not with placebo, decreased the levels of urease measured by the urea breath test and H. pylori stool antigen (both biomarkers of H. pylori colonization) and serum pepsinogens I and II (biomarkers of gastric inflammation). Values recovered to their original levels 2 months after treatment was discontinued. Daily intake of sulforaphane-rich broccoli sprouts for 2 months reduces H. pylori colonization in mice and improves the sequelae of infection in infected mice and in humans. This treatment seems to enhance chemoprotection of the gastric mucosa against H. pylori-induced oxidative stress.

 

Sulforaphane absorption and excretion following ingestion of a semi-purified broccoli powder rich in glucoraphanin and broccoli sprouts in healthy men.

From: http://www.ncbi.nlm.nih.gov/pubmed/21240766

Nutr Cancer. 2011;63(2):196-201. doi: 10.1080/01635581.2011.523495, Cramer JMJeffery EH.

Abstract

Sulforaphane (SF) is a chemopreventive isothiocyanate (ITC) derived from the myrosinase-catalyzed hydrolysis of glucoraphanin, a thioglucoside present in broccoli. Broccoli supplements often contain glucoraphanin but lack myrosinase, putting in question their ability to provide dietary SF. This study compared the relative absorption of SF from air-dried broccoli sprouts rich in myrosinase and a glucoraphanin-rich broccoli powder lacking myrosinase, individually and in combination. Subjects (n=4) each consumed 4 meals consisting of dry cereal and yogurt with 2 g sprouts, 2 g powder, both, or neither. Blood and urine were analyzed for SF metabolites. The 24 h urinary SF recovery was 74%, 49%, and 19% of the dose ingested from broccoli sprouts, combination, and broccoli powder meals, respectively. Urinary and plasma ITC appearance was delayed from the broccoli powder compared to the sprouts and combination. A liver function panel indicated no toxicity from any treatment at 24 h. These data indicate a delayed appearance in plasma and urine of SF from the broccoli powder relative to SF from myrosinase-rich sprouts. Combining broccoli sprouts with the broccoli powder enhanced SF absorption from broccoli powder, offering the potential for development of foods that modify the health impact of broccoli products.

One of several challenges in design of clinical chemoprevention trials is the selection of the dose, formulation and dose schedule of the intervention agent. Therefore, a cross-over clinical trial was undertaken to compare the bioavailability and tolerability of sulforaphane from two of broccoli sprout-derived beverages: one glucoraphanin-rich (GRR) and the other sulforaphane-rich (SFR). Sulforaphane was generated from glucoraphanin contained in GRR by gut microflora or formed by treatment of GRR with myrosinase from daikon (Raphanus sativus) sprouts to provide SFR. Fifty healthy, eligible participants were requested to refrain from crucifer consumption and randomized into two treatment arms. The study design was as follows: 5-day run-in period, 7-day administration of beverages, 5-day washout period, and 7-day administration of the opposite intervention. Isotope dilution mass spectrometry was used to measure levels of glucoraphanin, sulforaphane and sulforaphane thiol conjugates in urine samples collected daily throughout the study. Bioavailability, as measured by urinary excretion of sulforaphane and its metabolites (in approximately 12 hour collections after dosing), was substantially greater with the SFR (mean = 70%) than with GRR (mean = 5%) beverages. Interindividual variability in excretion was considerably lower with SFR than GRR beverage. Elimination rates were considerably slower with GRR allowing for achievement of steady state dosing as opposed to bolus dosing with SFR. Optimal dosing formulations in future studies should consider blends of sulforaphane and glucoraphanin as SFR and GRR mixtures to achieve peak concentrations for activation of some targets and prolonged inhibition of others implicated in the protective actions of sulforaphane.

SUMMARY

Broccoli–and especially broccoli sprouts with its high content of sulforaphane–contain important polyphenols, antioxidants, and Nrf2 activators that help make Ultimate Protector an outstanding nutritional supplement. Broccoli and broccoli sprouts have been used extensively in nutritional healing protocols for almost 25 years now.

Continued research shows a growing list of health benefits for these nutritional substances, especially relating to Nrf2 activity and ability to provide significant chemoprevention. They add an important vegetable profile to the ingredient mix in Ultimate Protector™.

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