HPDI’s amazing IMMUNE-ASSIST™ mushroom formula is a combination of more than 200 different polysaccharides, derived from the enzymatic breakdown of complex organic plant material from six different species of organically grown medicinal mushrooms. These include Agaricus blazei, Cordyceps hybrid (sinensis and militaris), Lentinula edodes (shiitake), Grifola frondosa (maitake), Ganoderma lucidum (Reishi), and Coriolus versicolor.
IMMUNE-ASSIST™ Daily Formula contains simple polysaccharides similar to many other products on the market, but it also contains much more complex polysaccharides like the cross-linked beta mannans and beta-glucans into the same molecule. This is why Immune-Assist™ shows such a greater range of immuno-modulation bioactivity than other bran based supplements. Included among the important substances in Immune-Assist™ are Arabinoxylane, Lentinan, Grifolan (Dr. Nanba’s original Maitake D-Fraction), PSK and PSP, and Active Hemicellulose Correlated Compound (AHCC).
Many mushroom-derived polysaccharides appear to fit the accepted criteria for immunomodulators or biological response modifiers (BRM) compounds. They cause no harm and place no additional stress on the body, they assist the body to adapt to the various environmental and psychological stresses, and they have a non-specific action on the body, supporting all the major systems, including nervous, hormonal, and immune systems, as well as regulatory functions.
MEDICINAL MUSHROOM EXTRACTS: ONE OF THE MOST POWERFUL IMMUNE MODULATORS KNOWN
Recent scientific research has shown that medicinal mushrooms grown on vegetable sources (such as millet, rice bran, buckwheat, milo, etc.) enzymatically activate a process whereby complex cross-linked polysaccharides from the vegetable sources are converted to biologically active immunomodulators. As you will see from the discussion below, the polysaccharides produced by this process are effective and safe immune stimulants.
Medicinal mushroom research has focused on discovering compounds that can modulate positively or negatively the biological response of immune cells. Certain mushroom derived-glucans and polysaccharide-bound proteins have been shown to act as immunomodulators, where these polymers interact with the immune system to upregulate or downregulate specific aspects of the responses of the host and this may result in various therapeutic effects.
Whether certain compounds enhance or suppress immune responses can depend on a number of factors including dosage, route of administration, timing and frequency of administration, mechanism of action or the site of activity.
The most effective polysaccharides isolated from mushrooms (fruit-body, submerged, cultured mycelial biomass or liquid culture broth) are either water-soluble β-D-glucans, β-D-glucans with heterosaccharide chains of xylose, mannose, galactose, or uronic acid or β-D-glucan-protein complexes – proteoglycans.
While the role of medicinal mushrooms in immunomodulation represents the central theme of much of the conducted research, it is pertinent to observe that many of the medicinal mushrooms have been highly valued for other medicinal properties including cholesterols control, blood pressure support, blood sugar support, assistance with viral and bacterial balance, and antioxidant and free radical scavenging.
The safety criteria for mushroom-derived β-glucans have been exhaustively carried out in pre-clinical experiments. Acute, subacute, and chronic toxicity tests have been carried out together with administration during pregnancy and lactation with no adverse effects. There were no anaphylactic reactions and no effects in mutagenicity and haemolysis tests, blood coagulation and a wide range of other regulatory tests. There was no evidence of genotoxicity. Similar results have been obtained with other β-glucans. When applied to humans in Phase 1 clinical tests, the β-glucans demonstrate remarkably few adverse clinical reactions.
In the 2001 report Medicinal Mushrooms: Their Therapeutic Properties and Current Medical Usage, a wide variety of mushroom polysaccharides, including Lentinan (from L. edodes), Schizophyllan (from S. commune), PSK and PSP (from Trametesversicolor), and Grifron-D (from the Maitake mushroom G. frondosa) and others are described, and their properties are shown to satisfy the criteria for biological response modifiers. Many of these mushroom-derived polymers potentiate the host’s innate (non-specific) and acquired (specific) immune responses in a similar manner, where they activate many kinds of immune cells that are vitally important for the maintenance of homeostasis.
Key innate responses that are stimulated by these mushroom derived-β-glucans or polysaccharide-protein complexes include host T-cells (such as cytotoxic macrophages, monocytes, neutrophils, natural killer cells, and dendritic cells) and chemical messengers (cytokines such as interleukins, interferon and colony stimulating factors) that trigger complement and acute phase responses. Moreover, mushroom polysaccharides or polysaccharide-protein complexes are considered as multi-cytokine inducers that are able to induce gene expression of various immunomodulatory cytokines and cytokine receptors.
In addition, acquired responses are also enlisted, where lymphocytes that govern antibody production (B cells) and cell-mediated cytotoxicity (T-cells) are stimulated. While the immune system is shrouded in tremendous complexity, our current understanding shows that it is regulated in an orchestrated dynamic manner.
Mushroom-derived polysaccharides have shown therapeutic activities in both pre-clinical models and in clinical trials. Although the mechanism of their action is still not completely clear, Lentinan, Schizophyllan, PSP, PSK and other mushroom polysaccharides appear to mediate their activity by activation or augmentation of the host’s immune system (via stimulated cytotoxic macrophages, cytotoxic T-cells and antibody-mediated cytoxicity of targeted cells), rather than direct cytotoxicity.
Thus, both cell-mediated immune responses against the target T-cells initiated by macrophage-lymphocyte interactions and cytoxicity induced by antibodies to target T-cells are believed to contribute to the elimination of abnormal cells. Recent evidence suggests that several mushroom polysaccharides may also possess cytotoxic properties. Grifron-D from G.fondosa mushroom was reported to induce apoptosis (programmed cell death) in human prostate cell-lines.
IMMUNE-ASSIST™ DAILY FORMULA INCORPORATES POLYSACCHARIDE EXTRACTS FROM SIX MEDICINAL MUSHROOMS
In China, Japan, Korea, and more recently in the USA, hundreds of mushroom species have been studied during the past 30 years. Extracts from most of the medicinal mushrooms show a common property of enhancing immune function by modulating cell-mediated immunity. Simply put, such mushroom extracts seem to turn on cells in the immune system, which appear to have significant healing properties. In fact, three different drugs extracted from mushrooms have been approved by the Japanese equivalent of FDA (that is, the Japanese Health and Welfare Ministry). These three are lentinan, derived from shiitake; PSK, derived from coriolus versicolor; and schizophyllan, derived from suehirotake.
Based on the latest research a USA-based company (Aloha Medicinals, Inc.) has formulated for Health Products Distributors, Inc. IMMUNE-ASSIST™ Daily Formula. This formula contains more than 200 different polysaccharides, derived from the enzymatic breakdown of complex organic plant material from six different species of medicinal mushrooms. These include Agaricus blazei, Cordyceps hybrid (sinensis and militaris), Lentinula edodes (shiitake), Grifola frondosa (maitake), Ganoderma lucidum (Reishi), and Coriolus versicolor.
RESEARCH RELATED TO MUSHROOMS CONTAINED IN IMMUNE-ASSIST™
Shiitake is now the most popular and most cultivated exotic mushroom in the world. In China, shiitake has a history that dates back to the Ming Dynasty (1368–1644 ACE). The mushroom was used not only as a food but was taken as a remedy for upper respiratory diseases, poor blood circulation, liver trouble, exhaustion and weakness, and to boost chi, or life energy. It was also believed to prevent premature aging.
Coriolus (or Trametes) versicolor is the most thoroughly clinically researched mushroom. An extract of Coriolus versicolor known as PSK is sold in Europe and Japan. It is an immunostimulant; demonstrates anti-viral activity; enhances T-cell proliferation; and has been shown to improve both disease-free and survival rates in patients.
Maitake may be even more potent than any of the other mushrooms previously studied. This legendary giant mushroom has been studied for its anti neoplastic, anti-diabetic, anti-hypertensive, and anti-hyperlipemic effects since the mid-1980s. Its anti-HIV activity in vitro was demonstrated in tests conducted by the Japan Institute of Health and the US National Cancer Institute in early 1992. Among various extracts obtained from the Maitake mushroom, a specific extracted fraction named Maitake D-fraction is the active constituent. This extract contains beta-1, 3-glucans and beta-1, 6-glucans protein-bound polysaccharides. It has demonstrated remarkable cell-protective activity by activating the immune system through oral administration.
The Chinese have long used Cordyceps sinensis and militaris to promote overall good health, and modern research indicates that it does indeed support liver, kidney, heart, and immune system function. Cordycepshas been used to protect the bone marrow and digestive systems of mice from whole body irradiation. One experiment noted that Cordyceps may protect the liver. An experiment with mice indicated the mushroom may have an anti-depressant effect.
Researchers have observed that Cordyceps has a hypoglycemic effect and may be beneficial for people with insulin resistance. Cordyceps mushroom extracts have been shown to stimulate the number of T helper cells, prolong the survival of lymphocytes, enhance TNF-alpha and interleukin 1 production, and increase the activity of natural killer cells. One study indicates that cordyceps can stimulate progesterone production in animal cells.
Reishi possess immunomodulary and immunotherapeutic activities supported by studies on polysaccharides, terpene, and other bioactive compounds isolated from fruiting bodies and mycelia of this fungus. It has also been found to inhibit platelet aggregation, and to lower blood pressure (via inhibition of angiotensin-converting enzyme), cholesterol, and blood sugar.
In an animal model, Reishi has been reported to prevent metastasis, with potency comparable to Lentinan from shiitake mushrooms. The mechanisms by which Reishi may target different stages of abnormal growth development include: 1) inhibition of angiogenesis (formation of new blood vessels created to supply nutrients to the abnormal cell) mediated by cytokines, 2) cytotoxicity, 3) inhibition of migration of the cells and 4) inducing and enhancing apoptosis. Besides effects on mammalian physiology, Reishiis reported to have anti-bacterial and anti-viral activities. Reishi is reported to exhibit direct anti-viral effects with the following viruses: HSV-1, HSV-2, and influenza.
Agaricus blazei is an edible mushroom native to Brazil and cultivated in Japan and the USA for its medicinal uses. It has been used to treat arteriosclerosis, hepatitis, hyperlipidemia, diabetes, dermatitis, and neoplasms. In vitro experiments and studies done in mice have shown that Agaricus has immunomodulatory and antimutagenic properties. The polysaccharides and anti-angiogenic compounds present in Agaricus are thought to be responsible for its therapeutic properties. Such effects are believed to be exerted by immunopotentiation or direct inhibition of angiogenesis.
ACTIVE HEMICELLULOSE CORRELATED COMPOUND (AHCC) AS A COMPONENT OF IMMUNE-ASSIST™ DAILY FORMULA
AHCC is produced by from the enzymatic action of vegetable sources with mycelial extracts from several different mushrooms. There is about four times more AHCC in each dose of Immune-Assist™ than there is in other AHCC products on the market.
AHCC is a food substance that contains a broad range of polysaccharides. It is believed that a special polysaccharide with a molecular weight of about 5,000 and an alpha 1,4 glucan linkage in this mushroom extract is primarily responsible for the powerful immune enhancing effects on natural killer cells. A heavier polysaccharide in the extract appears to have a powerful stimulating effect on macrophages which, in turn, further stimulates the immune system including a number of cytokines (Interleukin-2, Interleukin-12, TNF, and Interferon). Furthermore, some research has indicated that components of AHCC may have direct cytotoxic effects on unhealthy cells.
NATURAL KILLER CELLS
The human immune system is comprised of more than 130 subsets of white blood cells. Natural Killer (NK) cells make up roughly 15% of all human white blood cells. They provide the first line of defense for dealing with any form of invasion to the body. Each NK cell contains several small granules that act as chemical destroyers. Once an NK cell has recognized an unwanted cell, for example, it attaches itself to the cell’s outer membrane and injects these granules directly into the interior of the cell. The granules then destroy the cell within five minutes. The undamaged NK cell then moves on to other cells and repeats the process. When the immune system is particularly strong, active NK cells will often take on more than one cell or other infected cells at the same time.
NK CELL ACTIVITY, NOT NUMBER, DETERMINES THE STRENGTH OF THE IMMUNE SYSTEM
Unlike other white blood cells, inadequate numbers of NK cells are very rarely a problem. Instead, it is the activity of the cells that generally determines whether one is sick or healthy. As long as the NK cells are active, everything remains under control. If NK cells lose their ability to either recognize or destroy the invader, however, the situation can deteriorate rapidly. In many patients with serious health conditions, NK cell activity is probably the primary criteria for estimating the chances of survival. It is commonly accepted that when NK cells cease to function, the end is near.
In addition, research has now confirmed that individuals with low NK cell activity are significantly more susceptible to autoimmune diseases, chronic fatigue syndrome, viral infections and the development of abnormal growths.
Doctors can test NK cell activity with a test called the NK cell function test. Basically, a blood sample is taken from the patient and placed in a vial containing appropriate live cells. After four hours, a count is taken to determine what percentage of the cells have been destroyed by the NK cells. The higher the percentage, the more active the cells. This test is referred to as the four hour Chromium-release assay. Your doctor can order the test from Immune Sciences Lab in Beverly Hills, CA at (310) 657-1077.
HOW IMMUNE-ASSIST™ DAILY FORMULA INCREASES NK CELL ACTIVITY AND IMMUNITY
The capacity of Immune-Assist™ to boost NK activity and overall immunity appears to stem from the following:
1) It increases the number of explosive granules in NK cells. The more granules an NK cell carries, the more unhealthy cells it can destroy.
2) Oral ingestion can increase NK activity as much as 300% (or even higher).
3) It increases interferon (IFN) levels. Interferon is another potent compound produced by the body that both inhibits the replication of viruses and other parasites and increases NK cell activity.
4) It increases the formation of TNFs. TNFs are a group of proteins that help destroy unwanted cells.
5) It increases number and the activity of other lymphocytes, especially T-cells (up to 200%) and macrophages.
6) It stimulates cytokine (IL-2, IL-12, TNF, and IFN) production, which stimulates immune function.
COMPOSITION: Two vegetarian capsules provide the following percentage of the Daily Value:
% Daily Value
Proprietary Beta-Glucan complex plus nucleosides and other bioactive compounds extracted from six well-known, organically grown medicinal mushrooms: Agaricus blazei, Cordyceps sinensis and Cordyceps militaris, Lentinula edodes, Grifola frondosa, Ganoderma lucidum, and Coriolus versicolor.
* No established Daily Value
DIRECTIONS: As a dietary supplement take two capsules per day in divided doses, or as recommended by a health care professional. In severe conditions, we suggest six (6) capsules per day for two weeks to build up immune activity, then maintaining a dosage of two (2) capsules per day. Alternatively, Immune-Assist™ can be taken at the time of exposure or first signs of illness, in which case we recommend taking two caps three times per day.
INGREDIENTS: IMMUNE-ASSIST™ contains a proprietary organic grown blend grown on organic white milo (growing substrate) and veggie capsule.
IMMUNE-ASSIST™ does not contain: wheat, rye, oats, corn, barley, gluten, soy, egg, dairy, yeast, GMOs, sugar, wax, preservatives, colorings, or artificial flavorings.
Looking for an advanced antioxidant formula? Already using or recommending vitamin C? Curious about cellular Nrf2 activation? Look no further than PRO-C™.
PRO-C™ is among the most effective antioxidant formulas available. It is an HPDI foundational supplement that works most effectively when used with multivitamins, essential fats, and superfoods. However, it is also an excellent standalone formula that can rapidly provide the body with extremely high protection from free radicals.
We ourselves have taken PRO-C daily for many years with excellent results. Our personal experience together with detailed feedback from health professionals and end-users affirms the effectiveness of PRO-C as a super-antioxidant–vitamin C-Nrf2 activator formula.
PRO-C provides 500 mg of buffered vitamin C per capsule (buffered with calcium, magnesium, and zinc) along with grape extract (seed, skin, pulp) and green tea extract (95% polyphenols). In addition, we include a special combination of the “network antioxidants” l-glutathione (reduced), n-acetyl-l-cysteine (NAC), r-lipoic acid, and selenium. Vitamin B2 and Vitamin B6 in coenzyme forms support the enzymatic effectiveness of the “network antioxidants”. The formula works so well because this combination of ingredients leverages the antioxidant power of vitamin C, grape extract, green tea extract, and the other nutrients to act synergistically in order to maximize effectiveness.
FORMULATION HISTORY AND THE SCIENCE BEHIND PRO-C™
What you may not know is the history of the development PRO-C and the scientific knowledge on which Dr. Hank Liers based his formulation of it.
Dr. Hank formulated his first product in 1989. It was a potent antioxidant formula he called PYC-C™ (sounds like “pixie”). PYC-C consisted of a combination of buffered Vitamin C (including magnesium, calcium, and zinc ascorbates) and pycnogenols from pine bark.
By 1997 Dr. Hank had gathered a great deal of new scientific information regarding green tea catechins and the nutrients termed “network antioxidants” by Dr. Lester Packer, director of Packer Lab at University of California, Berkeley. Beyond this information, Dr. Hank studied additional research regarding how various nutrients worked together synergistically. At that point, he was ready to formulate the new, improved PRO-C™ super antioxidant formula.
PRO-C combines the ingredients of PYC-C (now known as OPC-C™) and uses grape pulp, skin, and seed extract with green tea extract (with high polyphenols >95% and EpiGalloCatechinGalate (EGCG) >45%), n-acetyl-l-cysteine (NAC), reduced glutathione (GSH), R-lipoic acid, selenium, and coenzyme Vitamins B2 and B6.
HPDI launched PRO-C™ in late 1997. It rapidly became one of our best-selling products. Our customers raved about how effective it was for them if they felt like they were “coming down with something” (like a cold, flu, virus, infection, etc.). Greater skin elasticity greatly helped pregnant women avoid stretch marks and episiotomies. Today, we highly recommend its use together with our other Foundational Supplements to ensure optimal health and anti-aging effects.
THE PRO-C™ SUPER ANTIOXIDANT FORMULA
PRO-C™ super antioxidant formula is extremely synergistic, especially in so far as it increases the body’s ability to quench free radicals in its aqueous (i.e., water-based) compartments. Because antioxidants may become free radicals themselves after they have done their job, the body has developed an elaborate system for recovery of oxidized antioxidants.
Dr. Lester Packer was the primary researcher investigating the synergistic character of antioxidants. He made this statement in his interview with Dr. Richard Passwater after publication of Packer’s The Antioxidant Miracle (1999):
” [The major theme of] The Antioxidant Miracle is that antioxidants work in a coordinated manner. They interact with one another, and this interaction, which we like to call the antioxidant network, is very important to the overall antioxidant defense that we possess. The key members of the antioxidant network are vitamin E and vitamin C, but there are other participants in this network. These are thiol antioxidants, antioxidants that contain sulfur groups in the body. Glutathione perhaps is the best known of these, but there are other sulfur-containing antioxidants that also are very important.”
Dr. Packer continues:
“This whole antioxidant network works like an orchestra depending on individuals who have, of course, different complements of antioxidants depending upon their nutritional regimens and the individuality of their own body metabolisms. The idea behind having a network of antioxidants is that if one antioxidant happens to be deficient the others can compensate and still keep the antioxidant defense system strong.”
The following diagram shows some of the relationships in the antioxidant network and how they support each other.
Figure 1 – Dr. Packer’s Antioxidant Network
We see, for example, reduced glutathione (GSH) has the ability to reduce oxidized Vitamin C back to its unoxidized state. Vitamin C reduces oxidized Vitamin E back to its unoxidized state, and both reduces glutathione and spares it for other important functions, including detoxification and immune enhancement.
Many polyphenols (e.g., oligomeric proanthocyanidins (OPCs), anthocyanidins and catechins) found in red grape and green tea extracts spare Vitamin C and glutathione in the body, as well as operate as powerful antioxidants, anti-inflammatories, and connective tissue strengtheners.
Grapes provide antioxidant nutrients such as polyphenols, OPCs, anthocyans, and resveratrol.
R-Lipoic Acid (see abstracts below) operates as an antioxidant both in its oxidized and reduced states, reduces the oxidized forms of both Vitamin E and Vitamin C, and and has been shown to enhance glutathione levels. Because several of these substances are able to protect Vitamin E contained in cell membranes, this combination also has a significant beneficial effect on the fat soluble antioxidant status of the body!
The nutrients in PRO-C have been carefully selected and balanced to provide optimal effects, especially as related to free radical protection, detoxification, immune system enhancement, connective tissue strengthening, and reduction of inflammation. PRO-C therefore provides outstanding nutritional support in a wide variety of conditions of poor health, as well as acts to support and maintain a state of health and well-being.
It the last several years the research results on Nrf2 activators have become well known and products developed that take advantage of these nutrients. For details see our blog article Natural Phytochemical Nrf2 Activators for Chemoprevention. Researchers have been studying specifically how enzyme-activating substances such as OPCs and anthocyans activate a transcription factor known as Nrf2 that causes the body to endogenously produce higher levels of a wide variety of protective enzymes including superoxide dismutase (SOD), catalase, and glutathione peroxidase.
Although we did not know about Nrf2 activators in 1997 when we formulated PRO-C, we have subsequently learned that four of the ingredients in the formula have powerful Nrf2 activity. These include grape seed extract, green tea extract, NAC, and r-lipoic acid. With this knowledge, we now understand that PRO-C provides both powerful external antioxidants (with extremely high ORAC5.0 values) that support redox cycles within the body, but also provides ingredients that allow the body to endogenously produce powerful protective enzymes for even greater free-radical protection and health.
PRO-C™ ANTIOXIDANT FORMULA INGREDIENTS
PRO-C contains buffered vitamin C (in the form of powdered calcium, magnesium, and zinc ascorbates), high-potency grape extract (from grape pulp, skins, and seeds), green tea extract (with>95% polyphenols and >45% EGCG), reduced glutathione, N-Acetyl-L-Cysteine (NAC), R-lipoic acid, coenzyme forms of vitamin B2 (R5P) and vitamin B6 (P5P), and selenium.
Below we will discuss each ingredient and show some of the research that confirms its effectiveness.
Vitamin C typically is called l-ascorbic acid or ascorbate and is an essential nutrient for humans and other animal species. The term “vitamin C” refers to a number of vitamins that have vitamin C activity in animals, including ascorbic acid and its salts (e.g., magnesium ascorbate, calcium ascorbate, sodium ascorbate, etc.), and some oxidized forms such as dehydroascorbate and semidehydroascorbate.
Vitamin C is known to perform many critical functions within the body involving detoxification, tissue building, immune enhancement, pain control, and controlling or killing pathogenic organisms. It is also known to be helpful for wound and bone healing, healthy skin and eyes, fighting infections, stress control, toxic exposure, and repairing damaged tissue of all types. For much more information on the many benefits of Vitamin C see our blog article Vitamin C – An Amazing Nutrient.
Below are two abstracts that show some of the beneficial effects of Vitamin C when used with other network antioxidants:
ABSTRACT 1: Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration.
Sastre J, Asensi M, Gasco E, Pallardo FV, Ferrero JA, Furukawa T, Vina J
In: Am J Physiol (1992 Nov) 263(5 Pt 2):R992-5
We have studied the effect of exhaustive concentric physical exercise on glutathione redox status and the possible relationship between blood glutathione oxidation and blood lactate and pyruvate levels. Levels of oxidized glutathione (GSSG) in blood increase after exhaustive concentric physical exercise in trained humans. GSSG levels were 72% higher immediately after exercise than at rest. They returned to normal values 1 h after exercise. Blood reduced glutathione (GSH) levels did not change significantly after the exercise. We have found a linear relationship between GSSG-to-GSH and lactate-to-pyruvate ratios in human blood before, during, and after exhaustive exercise. In rats, physical exercise also caused an increase in blood GSSG levels that were 200% higher after physical exercise than at rest. GSH levels did not change significantly. Thus, both in rats and humans, exhaustive physical exercise causes a change in glutathione redox status in blood. We have also found that antioxidant administration, i.e., oral vitamin C, N-acetyl-L- cysteine, or glutathione, is effective in preventing oxidation of the blood glutathione pool after physical exercise in rats.
The effect of glutathione and vitamins A, C, and E on acute skin flap survival.
Hayden RE, Paniello RC, Yeung CS, Bello SL, Dawson SM
In: Laryngoscope (1987 Oct) 97(10):1176-9
Vitamins A, C, and E act as antioxidants and as free radical scavengers in biological systems. Glutathione is involved in several reactions in vitamin metabolism and also plays an important role in cell membrane protection against lipid peroxidation by free radicals. We sought to use these natural defense mechanisms against oxygen free radicals formed during reperfusion of ischemic skin flaps. An acute axial random skin flap model was utilized in the rat. Vitamins or glutathione were administered by oral gastric tube or intravenously in the perioperative period, and survival of the flap was measured at 1 week. Glutathione, beta-carotene, ascorbic acid and alpha-D- tocopherol showed mean flap survival of 84% to 89%, each of which was significantly improved over saline controls (67% p less than .0005). The mechanisms and biochemistry of these vitamins, and their interactions with other vitamins and with glutathione, are discussed, along with clinical implications of free radical scavenging and skin flap survival.
Grape extract (seeds, skin, pulp) contain highly bioavailable bioflavonoid complexes that in research studies have been shown to have powerful antioxidant capability. The Oligomeric Proanthocyanidins (OPCs) in grape seed extract are able to strengthen collagen fibers in aging or damaged connective tissue and can act as a preventative against connective tissue degradation.
Some research indicates that anthocyans, which are found in extracts of grape skin and stems (but not in grape seed extract), can reduce oxidized glutathione while at the same time become reduced themselves. In addition, extracts of grape skin and stems (but not those of grape seed extract) contain a material called trans-resveratrol that has been shown to have chemopreventive effects.
ABSTRACT 3: Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice. Bagchi D, Garg A, Krohn RL, Bagchi M, Bagchi DJ, Balmoori J, Stohs SJ
In: Gen Pharmacol (1998 May) 30(5):771-6
1. The comparative protective abilities of a grape seed proanthocyanidin extract (GSPE) (25-100 mg/kg), vitamin C (100 mg/kg), vitamin E succinate (VES) (100 mg/kg) and beta-carotene (50 mg/kg) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lipid peroxidation and DNA fragmentation in the hepatic and brain tissues, as well as production of reactive oxygen species by peritoneal macrophages, were assessed. 2. Treatment of mice with GSPE (100 mg/kg), vitamin C, VES and beta-carotene decreased TPA-induced production of reactive oxygen species, as evidenced by decreases in the chemiluminescence response in peritoneal macrophages by approximately 70%, 18%, 47% and 16%, respectively, and cytochrome c reduction by approximately 65%, 15%, 37% and 19%, respectively, compared with controls. 3. GSPE, vitamin C, VES and beta-carotene decreased TPA-induced DNA fragmentation by approximately 47%, 10%, 30% and 11%, respectively, in the hepatic tissues, and 50%, 14%, 31% and 11%, respectively, in the brain tissues, at the doses that were used. Similar results were observed with respect to lipid peroxidation in hepatic mitochondria and microsomes and in brain homogenates. 4. GSPE exhibited a dose-dependent inhibition of TPA- induced lipid peroxidation and DNA fragmentation in liver and brain, as well as a dose-dependent inhibition of TPA-induced reactive oxygen species production in peritoneal macrophages. 5. GSPE and other antioxidants provided significant protection against TPA-induced oxidative damage, with GSPE providing better protection than did other antioxidants at the doses that were employed.
ABSTRACT 4: Clinical and capillaroscopic evaluation of chronic uncomplicated venous insufficiency with procyanidins extracted from vitis vinifera
Costantini A, De Bernardi T, Gotti A
In: Minerva Cardioangiol (1999 Jan-Feb) 47(1-2):39-46
BACKGROUND: The pharmacological treatment of non-complicated chronic venous insufficiency is a current and well-debated topic. The introduction of new products with action on the venous system, improved knowledge on the physiopathology of venous insufficiency and the possibility provided by new analytical instruments, have given new impulse to the consolidation of the clinical value of phlebotonics in this indication. METHODS: In light of this, 24 patients with non-complicated chronic venous insufficiency were treated with oral administration of Oligomeric Proanthocyanidins (Pycnogenols-OPC) 100 mg/day. To evaluate the therapeutic efficacy of the treatment, an instrumental evaluation by optical probe capillaroscope was employed in addition to the traditional subjective clinical parameters: swelling, itching, heaviness and pain. The videocapillaroscope examination was performed at the lower third of the leg and the first toe. Edema in the capillaroscopic field, the number of observable capillaries and the capillary dilatation were the parameter chosen to evaluate the efficacy of treatment. All patients completed the study with no reports of adverse events during the period of observation. RESULTS: The results obtained show a positive clinical response (improved or absent symptoms) in over 80% of patients, with significant improvement of symptoms already evident after the first 10 days of treatment. The mechanism of action of the OPCs explains the rapid reduction of the swelling of the lower limbs and correlated with this are the other evaluable symptoms: heaviness and itching. Particularly striking results were observed for itching and pain which completely disappeared during the course of therapy in 80% and 53% of the patients respectively. Noteworthy is the good correlation between the clinical and instrumental data, with improvement in a total of 70% of patients. CONCLUSIONS: The results obtained in the course of this clinical experience, with evident improvement already during the first weeks of treatment, the absence of adverse events added to the benefit of a once-a-day administration, justify the use of OPC in the treatment of non-complicated chronic venous insufficiency.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor that regulates antioxidant response element (ARE)-driven phase II detoxification enzymes. In this study, induction of phase II enzymes via Nrf2/ARE activation in the cytoprotective effect of crude polyphenol extract (CPE), oligomeric procyanidin fraction (OPF), and polymeric procyanidin fraction (PPF) from defatted grape seeds in HepG2 cells was evaluated. Among these treatments, the treatment with PPF significantly increased Nrf2 protein expression in the nuclear fraction. Treating the samples increased heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) protein expression in a dose-dependent manner, and PPF significantly increased the levels of phase II enzymes. Cellular generation of reactive oxygen species (ROS) were effectively reduced by PPF. These results suggest that pretreatment with PPF shows a cytoprotective effect by inhibiting ROS production and inducing HO-1 and NQO1 expression via Nrf2 activation in HepG2 cells.
GREEN TEA EXTRACT
Green tea extract is obtained from the unfermented leaves of Camellia sinensis for which numerous biological activities have been reported including: antimutagenic, antibacterial, hypocholesterolemic, antioxidant, and protective against tumorigenesis. Below we have selected a few of the many abstracts we have on file showing the benefit of green tea extract.
Green tea leaves are high in antioxidant polyphenols and catechins.
ABSTRACT 6: Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in cancer chemoprevention.
Khan SG, Katiyar SK, Agarwal R, Mukhtar H
In: Cancer Res (1992 Jul 15) 52(14):4050-2
Following the oral feeding of a polyphenolic fraction isolated from green tea (GTP) in drinking water, an increase in the activities of antioxidant and phase II enzymes in skin, small bowel, liver, and lung of female SKH-1 hairless mice was observed. GTP feeding (0.2%, w/v) to mice for 30 days significantly increased the activities of glutathione peroxidase, catalase, and quinone reductase in small bowel, liver, and lungs, and glutathione S-transferase in small bowel and liver. GTP feeding to mice also resulted in considerable enhancement of glutathione reductase activity in liver. In general, the increase in antioxidant and phase II enzyme activities was more pronounced in lung and small bowel as compared to liver and skin. The significance of these results can be implicated in relation to the cancer chemopreventive effects of GTP against the induction of tumors in various target organs.
ABSTRACT 7: INHIBITORY EFFECT OF SIX GREEN TEA CATECHINS AND CAFFEINE ON THE GROWTH OF FOUR SELECTED HUMAN TUMOR CELL LINES. In: Anticancer Drugs (1996 Jun) 7(4):461-8
Institutional address: Department of Pharmacology and Toxicology College of Pharmacy University of Arizona Tucson 85721 USA.
Green tea is an aqueous infusion of dried unfermented leaves of Camellia sinensis (family Theaceae) from which numerous biological activities have been reported including antimutagenic, antibacterial, hypocholesterolemic, antioxidant, antitumor and cancer preventive activities. From the aqueous-alcoholic extract of green tea leaves, six compounds (+)-gallocatechin (GC), (-)-epicatechin (EC), (-)- epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)- epigallocatechin gallate (EGCG) and caffeine, were isolated and purified. Together with (+)-catechin, these compounds were tested against each of four human tumor cells lines (MCF-7 breast carcinoma, HT-29 colon carcinoma, A-427 lung carcinoma and UACC-375 melanoma). The three most potent green tea components against all four tumor cell lines were EGCG, GC and EGC. EGCG was the most potent of the seven green tea components against three out of the four cell lines (i.e. MCF-7 breast cancer, HT-29 colon cancer and UACC-375 melanoma). On the basis of these extensive in vitro studies, it would be of considerable interest to evaluate all three of these components in comparative preclinical in vivo animal tumor model systems before final decisions are made concerning which of these potential chemopreventive drugs should be taken into broad clinical trials.
GLUTATHIONE AND N-ACETYL-L-CYSTEINE (NAC)
Glutathione and NAC (a major precursor of glutathione) both provide important protection against toxins and free radicals, and can strengthen the immune system. Glutathione is considered to be one of the most important protective substances in the human body with almost 60% of liver detoxification accounted for by this key substance. In addition, glutathione is one of the most potent anti-viral substances known.
Some research has indicated that glutathione may not be able to enter easily into certain types of cells, but NAC is able to enter these cells and be converted into glutathione once inside the cell. Thus, the combination of glutathione and NAC appear to be more potent than either alone.
ABSTRACT 8 GSH rescue by N-acetylcysteine.
Ruffmann R Wendel A
In: Klin Wochenschr (1991 Nov 15) 69(18):857-62
Reduced glutathione (GSH) is the main intracellular low molecular weight thiol. GSH acts as a nucleophilic scavenger and as an enzyme-catalyzed antioxidant in the event of electrophilic/oxidative tissue injury. Therefore, GSH has a major role as a protector of biological structures and functions. GSH depletion has been recognized as a hazardous condition during paracetamol intoxication. Conversely, GSH rescue, meaning recovery of the protective potential of GSH by early administration of N-acetylcysteine (NAC), has been found to be life-saving. Lack of GSH and electrophilic/oxidative injury have been identified among the causes of the adult respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), and the acquired immunodeficiency syndrome (AIDS). Experimental and early clinical data (in ARDS) point to the role of NAC in the treatment of these conditions. Recently, orally given NAC has been shown to enhance the levels of GSH in the liver, in plasma, and notably in the bronchoalveolar lavage fluid. Rescue of GSH through NAC needs to be appreciated as an independent treatment modality for an array of different disease, all of which have one feature in common: pathogenetically relevant loss of GSH.
ABSTRACT 9 Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine.
Bridgeman MM Marsden M MacNee W Flenley DC Ryle AP
In: Thorax (1991 Jan) 46(1):39-42
N-acetylcysteine (600 mg/day) was given to patients by mouth for five days before bronchoscopy and bronchoalveolar lavage to determine whether N-acetylcysteine could increase the concentrations of the antioxidant reduced glutathione in plasma and bronchoalveolar lavage fluid. Bronchoalveolar lavage was performed 1-3 hours (group 2, n = 9) and 16-20 hours (group 3, n = 10) after the last dose of N-acetylcysteine and the values were compared with those in a control group receiving no N-acetylcysteine (group 1, n = 8). N-Acetylcysteine was not detected in plasma or lavage fluid. Plasma concentrations of cysteine, the main metabolite of N-acetylcysteine and a precursor of reduced glutathione, were greater in the groups receiving treatment (groups 2 and 3) than in group 1. Cysteine concentrations in lavage fluid were similar in the three groups. Concentrations of reduced glutathione were greater in both plasma and lavage fluid in group 2 than in group 1. These data suggest that N-acetylcysteine given by mouth is rapidly deacetylated to cysteine, with resulting increases in the concentrations of cysteine in plasma and of reduced glutathione in plasma and the airways, which thus temporarily increase the antioxidant capacity of the lung.
R-LIPOIC ACID / ALPHA-LIPOIC ACID
R-Lipoic Acid is normally made at low levels in the human body, where it functions primarily as an important metabolic nutrient in the conversion of pyruvic acid into acetyl coenzyme A. As such, it plays a crucial role in the metabolism of both fats and carbohydrates into energy. In addition, r-lipoic acid functions as an extremely powerful antioxidant capable of trapping many different types of free radicals in the body.
Because it is both water and fat soluble, lipoic acid is able to operate in a broader range of body tissues than most other antioxidants. Its small size allows lipoic acid to enter areas of the body not easily accessible to many other substances; this allows lipoic acid, for example, to enter the cell nucleus and prevent free-radical damage to DNA.
Because it is such a powerful antioxidant and can easily function as such in both a reduced and oxidized state, lipoic acid is able to protect other important antioxidants such as glutathione, Vitamin E, and Vitamin C. R-lipoic acid is also able to chelate heavy metals such as lead, cadmium, mercury, free iron, and free copper out of the body.
Below we provide relevant scientific abstracts from our database regarding R-Lipoic acid.
ABSTRACT 10: Alpha-Lipoic acid as a biological antioxidant.
Packer L Witt EH Tritschler HJ
In: Free Radic Biol Med (1995 Aug) 19(2):227-50
alpha-Lipoic acid, which plays an essential role in mitochondrial dehydrogenase reactions, has recently gained considerable attention as an antioxidant. Lipoate, or its reduced form, dihydrolipoate, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, hypochlorous acid, peroxyl radicals, and singlet oxygen. It also protects membranes by interacting with vitamin C and glutathione, which may in turn recycle vitamin E. In addition to its antioxidant activities, dihydrolipoate may exert prooxidant actions through reduction of iron. alpha-Lipoic acid administration has been shown to be beneficial in a number of oxidative stress models such as ischemia-reperfusion injury, diabetes (both alpha-lipoic acid and dihydrolipoic acid exhibit hydrophobic binding to proteins such as albumin, which can prevent glycation reactions), cataract formation, HIV activation, neurodegeneration, and radiation injury. Furthermore, lipoate can function as a redox regulator of proteins such as myoglobin, prolactin, thioredoxin and NF-kappa B transcription factor. We review the properties of lipoate in terms of (1) reactions with reactive oxygen species; (2) interactions with other antioxidants; (3) beneficial effects in oxidative stress models or clinical conditions.
Alpha-lipoic acid (α-LA) is an important antioxidant that is capable of regenerating other antioxidants, such as glutathione (GSH). However, the underlying molecular mechanism by which α-LA regenerates GSH remains poorly understood. The current study aimed to investigate whether α-LA regenerates GSH by activation of Nrf2 to alleviate cadmium-induced cytotoxicity in HepG2 cells. In the present study, we found that cadmium induced cell death by depletion of GSH through inactivation of Nrf2. Addition of α-LA to cadmium-treated cells reactivated Nrf2 and regenerated GSH through elevating the Nrf2-downstream genes γ-glutamate-cysteine ligase (γ-GCL) and GR, both of which are key enzymes for GSH synthesis. However, blocking Nrf2 with brusatol in the cells co-treated with α-LA and cadmium reduced the mRNA and the protein levels of γ-GCL and GR, thus suppressed GSH regeneration by α-LA. Our results indicated that α-LA activated Nrf2 signaling pathway, which upregulated the transcription of the enzymes for GSH synthesis and therefore GSH contents to alleviate cadmium-induced cytotoxicity in HepG2 cells.
Selenium has been shown by clinical research to be a key mineral in the body’s defenses against free radicals and has been shown to be a major factor in reducing the symptoms of HIV infections and in the prevention of tumors. Selenium is used in conjunction with glutathione to form the powerful enzyme glutathione peroxidase that is responsible for detoxification of peroxides formed during the process of aerobic metabolism in humans and other animals.
ABSTRACT 12 Serum selenium concentrations in rheumatoid arthritis.
In: Ann Rheum Dis (1991 Jun) 50(6):376-8
O’Dell JR, Lemley-Gillespie S, Palmer WR, Weaver AL, Moore GF, Klassen LW
Selenium is a trace element and an essential part of the enzyme glutathione peroxidase, which protects cells from oxidative damage. Selenium has been shown to have antiproliferative, anti-inflammatory, antiviral, and immune altering effects. Serum selenium concentrations in 101 patients with seropositive rheumatoid arthritis were found to be significantly lower than those in 29 normal, healthy controls (mean (SD) 148 (42) v 160 (25) micrograms/l) and also lower than those in eight patients with fibrositis (148 (42) v 166 (25) micrograms/l). It is speculated that serum selenium concentrations may modulate the effect of viral or other infections in subjects with the appropriate genetic background and in this way enhance the development or progression of rheumatoid arthritis.
ABSTRACT 13 Studies on selenium in top athletes.
Dragan I, Ploesteanu E, Cristea E, Mohora M, Dinu V, Troescu VS
In: Physiologie (1988 Oct-Dec) 25(4):187-90
The authors performed a controlled trial in 18 top athletes (9 weight lifters and 9 rowers, girls) in order to make evident some chronic and acute effects (antioxidant) of selenium. Nonprotein–SH (essential glutathione), lipid peroxides (MDA-malondialdehyde), glucose-6-phosphate dehydrogenases (G-6-PDH) and fructose-1,6- diphosphate aldolase in serum, have been recorded initially on basal conditions, after 3 weeks of treatment (100 micrograms/day selenium or placebo) and again after 3 weeks of treatment, also on basal conditions, when crossing over the groups (between a free interval of 10 days). In another trial we registered these parameters on basal conditions and after two hours of hard training accompanied by a per oral administration of 150 micrograms selenium (respectively placebo). The results show significant changes under selenium treatment of the peroxides, G-6-PDH and light changes, not significant of the nonprotein–SH, changes which could suggest an antioxidant effect of this element.
VITAMINS B2 and B6 IN COENZYME FORMS
Vitamin B2 as coenzyme riboflavin-5-phosphate is a key vitamin that supports the regeneration of glutathione (via glutathione reductase). Vitamin B6 as coenzyme pyridoxal-5-phosphate is a key vitamin that supports the ability of glutathione to combine with toxic substances (via glutathione transferase) in the process of eliminating them from the body. They are especially effective in their coenzyme forms which allows them to be directly utilized by the body starting in the intestinal tract.
MAGNESIUM, CALCIUM, AND ZINC
Magnesium, zinc, and calcium synergistically work with (and enhance the effects of) the other ingredients in PRO-C. Minerals are especially needed as active components of enzymes that drive metabolic activity. For example, magnesium is required in the functioning of more than 325 types of enzymes.
PRO-C™ SUPER ANTIOXIDANT FORMULA BENEFITS
HIGHLY EFFECTIVE VITAMIN C FORMULA PLUS ANTIOXIDANTS. A complete vitamin C formula, a powerful antioxidant Formula, and Nrf2 activator combined in a single advanced supplement!
POWERFUL, SYNERGISTIC FREE-RADICAL QUENCHING FORMULA. PRO-C™ components work together to quench free radicals in your body. Vitamin C enables grape seed extract to function more effectively, and conversely grape seed extract potentiates vitamin C. Green tea extract boosts ORAC (Oxygen Radical Absorbance Capacity) value.
PROVIDES SIGNIFICANT AMOUNTS OF POWERFUL NRF2 ACTIVATORS (from Grape Extract, Green Tea Extract, NAC, and R-Lipoic Acid) that stimulate the production of the body’s own protective antioxidants including superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase.
SUPERIOR, BUFFERED (NON-ACIDIC) FORM OF VITAMIN C. Mineral Ascorbates never acidify your body, keeping you pH balanced. Staying alkaline is an important element in maintaining a healthy body.
RAPID ASSIMILATION. Capsule form ensures rapid uptake and assimilation in the body. You may also empty capsule contents into water, food, or directly Into mouth, if desired. Good, mildly tart taste!
COMPOSITION OF PRO-C™ SUPER ANTIOXIDANT FORMULA
One (1) vegetarian capsule of PRO-C provides the following percentages of the Daily Value:
% Daily Value
Vitamin C (from mineral ascorbates)
BioVin® Grape Extract
Green Tea Extract
Calcium (from calcium ascorbate)
Magnesium (from magnesium ascorbate)
Zinc (from zinc ascorbate)
Vitamin B2 (from riboflavin-5′-phosphate)
Vitamin B6 (from pyridoxal-5′-phosphate)
Selenium (from l-selenomethionine)
* No established Daily Value
DIRECTIONS: As a dietary supplement take 1–3 capsules or more daily in divided doses (i.e., spread out over the day), or as recommended by a health care professional. It initially may be useful to take up to 6 capsules per day in divided doses for one week. The contents of the capsule may be emptied into juice or food, as needed.
INGREDIENTS: PRO-C™ SUPER ANTIOXIDANT FORMULA contains only the highest-quality USP grade magnesium ascorbate, USP grade calcium ascorbate, BioVin® grape extract (greater than 75% polyphenols, 93% OPC, greater than 3.5% anthocyanidins from grape pulp, skins, and seeds, and a small amount of trans resveratrol), green tea extract (95% min. polyphenols and 45% min. EGCG), l-glutathione (reduced), USP grade n-acetyl-l-cysteine, USP grade zinc ascorbate, r-(+)-lipoic acid, riboflavin-5′-phosphate, pyridoxal-5′-phosphate, l-selenomethionine, the smallest amounts of microcrystalline cellulose and silica in a vegetarian capsule.
PRO-C™ does not contain wheat, rye, oats, corn antigen, barley, gluten, soy, egg, dairy, yeast, sugar, sulfates, phosphates (other than coenzyme forms), fats, chlorides, GMOs, wax, preservatives, colorings, or artificial flavorings.
HPDI foundational supplements are designed to provide a complete range of essential nutrients that complement a healthy diet and lifestyle. They help ensure sufficient levels of nutrients required for good health.
We define foundational supplements as basic or “core” supplements that should be part of everyone’s daily regimen. They are the foundation of a complete nutritional supplement program.
HPDI has a three-tiered system of nutritional supplements: 1) Foundational Supplements, 2) Enhancement Formulas, and 3) Specific-Condition Formulas. All three tiers comprise a complete nutritional supplement program.
When properly combined, these three tiers of nutritional supplements help create optimal health. This month, I explain how to use HPDI foundational supplements, the base or bottom tier of the system (see cone diagram below).
The HPDI supplement system can be visualized as a cone having a base of Foundational Supplements ascending toward an apex of Enhancement Formulas and Specific Condition Formulas.
The HPDI Supplement System includes six types of Foundational Supplements forming its base.
USING HPDI FOUNDATIONAL SUPPLEMENTS
My intent is to guide consumers and health care professionals to decide the foundational supplements that are best for their purposes, and that provide the most effective results.
We established the original three types of foundational supplements about 1988. We have always suggested that clients and health professionals take and/or recommend multivitamins, vitamin C and antioxidants, and essential fats.
About 10 years ago, we added high-RNA foods (like Rejuvenate! superfoods) as a fourth type of foundational supplement because research indicates dietary nucleic acids are essential nutrients—see our blog articles on nucleic acids, Benjamin S. Frank, MD, PhD, and about Rejuvenate! superfoods (Original, Plus, and Berries & Herbs).
Two categories of foundational supplements are new: gut health formulas and hydrogen formulas. Hank wrote an article (Amending the HPDI Foundational Program) about these changes in April. We added these two categories after much consideration regarding their benefits, and have written extensively about them in this blog (see resources section below).
The entire HPDI supplement system is depicted (above) as a cone. The six types of foundational supplements form the base of the cone. Enhancement Formulas and Specific-Condition formulas sit above toward the apex.
Ultimate Protector Nrf2 formula is a foundational supplement in the vitamin C / antioxidant category.
HOW I USE HPDI FOUNDATIONAL SUPPLEMENTS
I use all six types of HPDI foundational supplements. I take the following supplements (below) and present them here as an example of how they can be integrated into a complete supplement regimen. Foundational Supplements I take:
Taking one supplement from each of the six foundational supplement categories builds, supports, and maintains optimal health.
We at HPDI recommend everyone take one of each type of foundational supplement. That is, we suggest an individual select for personal use a multivitamin, vitamin C/antioxidant formula, essential fats formula, Rejuvenate!™ superfood (or other high-RNA superfood), hydrogen product, and at least one gut health product (depending on their gut-health needs).
Similarly we suggest health care professionals recommend for their clients one of each of the six types of foundational supplements.
The other two categories in the HPDI nutritional supplement system are Enhancement Formulas and Specific-Condition Formulas (see cone diagram). These are not foundational supplements. However, I include the supplements I take in these categories for the sake of completeness, as well as to show how Enhancement and Specific-Condition Formulas integrate with Foundational Supplements to form a complete supplement program providing a wide-range of essential nutrients required for health.
While I take supplements from all three categories (Foundationals, Enhancements, and Specific-Condition) in the HPDI supplement system, I always prioritize foundational supplements—I take them first—because they are base on which my personal supplement program rests.
Foundational supplements should be the base on which your supplement program—or those of your clients—rests, as well.
We have seen the results of taking a complete set of foundational supplements. They work because the nutrients they provide are needed by everyone.
Muti Two Caps is a high-potency multi with coenzyme forms for optimal utilization in the body.
FOUNDATIONAL SUPPLEMENTS: RESULTS
Individuals who take all types of foundational supplements do best in terms of optimizing health. The reason is that all six types provide nutrients required for good health.
I can attest that HPDI Foundational Supplements are effective for improving or maintaining good health. In addition, I have witnessed numerous instances where individuals benefit most greatly when taking all four–and now all six–types of foundational supplements.
Each of the six categories of foundational supplement provide unique benefits. Yet, each performs functions required by the human body for good health. That is one reason when they are combined they exert synergistic effects for health going far beyond the benefits of using, one, two, or three of the types of foundational supplements.
WHEN FOUNDATIONAL SUPPLEMENTS ARE NOT PRIORITIZED
I talk to people who may or may not take a multivitamin. And they may or may not take vitamin C. Yet, they may take calcium for their bones, glucosamine for their joints, and lutein for their eyes. Or they may take a low-potency, off-the-shelf multivitamin providing merely the RDA for all nutrients.
There is nothing wrong with individuals taking supplements they regard as important or useful. But that cannot guarantee that a wide range—and sufficient levels—of nutrients necessary for health are available to the body on a regular basis.
In fact, I regard the supplement intake programs of most persons to be “hit-or-miss.” They may consume nutrients important for a few functions in the body, yet fail to obtain other essential nutrients required for the nutrients they take to work most effectively. We have written extensively on this topic on our website and in blog articles (see below).
Not taking regularly a complete set of foundational supplements likely means key nutrients (and key levels of nutrients) go missing. Over time, this means fewer and lower levels of nutrients available to support the body’s needs for them at levels known to sustain the good health.
The best way to ensure a sufficient range of nutrients at plentiful levels is to take foundational supplements. After a baseline of nutrients is established by taking foundational supplements, additional supplements can be added, as necessary.
High-RNA foods like Rejuvenate! PLUS superfood provide dietary nucleic acids important for health.
A COMPLETE SYSTEM OF SUPPLEMENTS, INCLUDING FOUNDATIONALS
After obtaining sufficient levels of basic nutrients required for health, then a person can add (or you can recommend) specific nutrients or formulas that target certain problems or issues. This is the basis for HPDI development of Enhancement Formulas and Specific-Condition Formulas.
Nutritional supplements in the categories of Enhancement Formulas and Specific-Condition Formulas therefore “stack” on top of HPDI’s Foundational Supplements (see cone diagram above). In this way, a complete nutritional supplement program begins with the most essential nutrients and continues with customizations based on the unique needs of an individual.
Enhancement Formulas in the HPDI system are supplements we regard as falling into the next tier in terms of importance, at least for most people. They do not necessarily provide essential nutrients, and yet many people (including myself) benefit significantly from them.
HPDI Foundational Supplements collectively form the base tier of a complete nutritional supplement system comprised of three tiers: 1) Foundational Supplements (six types), 2) Enhancement Formulas (or simply “Enhancements”), and 3) Specific-Condition Formulas.
Foundational Supplements are necessary because they provide nutrients foundational to health. Taking them daily or recommending your clients take them daily can help mean big differences in health, nutrition, and quality of life.
We at HPDI design our nutritional supplements to be the most effective dietary supplements available. HPDI products are known for: 1) Advanced Formulation (including use of superior forms of nutrients), 2) Ultra-High Purity, 3) Avoidance of Harmful Ingredients, and 4) being made with Good Manufacturing Practices (GMP). For more details, please see The HPDI Difference and our Statement on Additives (Excipients).
At least 40 of HPDI’s products are formulated by Dr. Hank Liers. They fall in all categories in HPDI’s supplement system. They can be found under “Dr. Hank Liers original formulas.”
Omega Plus provides exceptionally well-balanced omega-3 and omega-6 fatty acids.
We frequently get questions from HPDI clients and resellers regarding foundational supplements. These questions include:
“Why did you add gut health and hydrogen products to your foundational supplements program?”
We found it necessary to add categories for gut health and hydrogen because they provide nutrients that are support the body and help ensure the foundational supplement system supports health most effectively. You can read more in previous blog articles (see below).
“Which is the better multivitamin: Multi Two or Mighty Multi-Vite!™?” It depends on whether you need more B vitamins or antioxidants. Multi Two provides more B vitamins and Mighty Multi-Vite™ provides more antioxidants and cofactors. I take a separate HPDI B-Complex-50 formula, so I take Mighty Multi-Vite!™ as my primary multivitamin.
“What are the differences between Rejuvenate!™ Original, PLUS, and Berries & Herbs superfoods?” They each provide about 340 mg of dietary nucleic acids. Original is the “greenest” with a large percentage of dietary nucleic acids coming from chlorella and spirunlina. PLUS is our most popular and 30% is identical to Original with more protein and a built-in multivitamin complex. Berries & Herbs contains no greens, yet more nucleic acids (390 mg), protein, and a built-in multivitamin. See our Rejuvenate! comparison page for more information.
“Should I take a vitamin C formula with antioxidants like PRO-C or one with Nrf2 activators like Ultimate Protector?” Both provide vitamin C and Nrf2 activators, but Ultimate Protector provides more types of Nrf2 activators. Ultimate Protector capsules are smaller than PRO-C capsules, so a daily dose may require taking more capsules.
“How important are hydrogen supplements?” Very important for energy production, recovery, antioxidant functions, and gut health. Hydrogen supplements like Active H2 and Megahydrate ensure high levels of hydrogen are available in the body.
What are your best products for supporting gut health? It depends on your needs: cleansing (Intestinal Rejuvenation Formula), probiotic/microbiome support (Prescript-Assist™), or tightening tight junctions in the gut (RESTORE)? We offer products for all these purposes.
These are just a few questions frequently asked about HPDI foundational supplements. If you need more information about products, please contact the HPDI office (800-228-4265) or email firstname.lastname@example.org.
You can also contact Fred Liers, PhD (520-400-0155) or Hank Liers, PhD (formulator) with questions you may have regarding products, ingredients, or formulation.
Ultimate Protector™ contains freeze dried cranberry, 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.
HEALTH BENEFITS OF CRANBERRIES
Cranberries (Vaccinium macrocarpon) are native to the boggy regions of temperate and subalpine North America and Europe. Although Native Americans used them extensively, they were first cultivated in the U.S. in the early 19th century. Cranberries grow on viney plants belonging to the heath family Ericaceae that also includes blueberries, bilberries, huckleberries, and bearberries (Arctostaphylos uva ursi). Cranberries contain tannins, fiber, anthocyanins (and other flavonoids), and Vitamin C. Their tannins prevent bacteria from attaching to cells. Consequently, cranberries have been used against infections, including urinary tract infections. In addition, cranberries may be helpful in protecting against heart disease and stroke.
Cranberries are an especially good source of antioxidant polyphenols. In animal studies, the polyphenols in cranberries have been found to decrease levels of total cholesterol and so-called “bad” cholesterol. Cranberries may also inhibit the growth of tumors in human breast tissue and lower the risk of both stomach ulcers and gum disease.
Here is a list of the antioxidant and anti-inflammatory phytonutrients in found in cranberries.
Type of PhytonutrientSpecific Molecules
Phenolic Acids hydroxybenzoic acids including vanillic acids;
—Phenolic Acids (cont.) hydroxycinnamic acids inculding caffeic,
—Phenolic Acids (cont.) coumaric, cinnamic, and ferulic acid
Anthocyanins cyanidins, malvidins, and peonidins
Flavonoids quercetin, myricetin, kaempferol
Triterpenoids ursolic acid
Other Cranberry Information
Cranberries hold significantly high amounts of phenolic flavonoid phytochemicals called oligomeric proanthocyanidins (OPC’s). Scientific studies have shown that consumption of the berries have potential health benefits against cancer, aging and neurological diseases, inflammation, diabetes, and bacterial infections.
Antioxidant compounds in cranberries including OPC’s, anthocyanidin flavonoids, cyanidin, peonidin and quercetin may prevent cardiovascular disease by counteracting against cholesterol plaque formation in the heart and blood vessels. Further, these compounds help the human body lower LDL cholesterol levels and increase HDL-good cholesterol levels in the blood.
Scientific studies show that cranberry juice consumption offers protection against gram-negative bacterial infections such as E.coli in the urinary system by inhibiting bacterial-attachment to the bladder and urethra.
In is known that cranberries turns urine acidic. This, together with the inhibition of bacterial adhesion helps prevent the formation of alkaline (calcium ammonium phosphate) stones in the urinary tract by working against proteus bacterial-infections.
In addition, the berries prevent plaque formation on the tooth enamel by interfering with the ability of the gram-negative bacterium, Streptococcus mutans, to stick to the surface. In this way cranberries helps prevent the development of cavities.
The berries are also good source of many vitamins like vitamin C, vitamin A, ß-carotene, lutein, zea-xanthin, and folate and minerals like potassium, and manganese.
Oxygen Radical Absorbance Capacity (ORAC) demonstrates cranberry at an ORAC score of 9584 µmol TE units per 100 g, one of the highest in the category of edible berries.
Cranberry fruit has been reported to have high antioxidant effectiveness that is potentially linked to its richness in diversified polyphenolic content. The aim of the present study was to determine the role of cranberry polyphenolic fractions in oxidative stress (OxS), inflammation and mitochondrial functions using intestinal Caco-2/15 cells. The combination of HPLC and UltraPerformance LC®-tandem quadrupole (UPLC-TQD) techniques allowed us to characterize the profile of low, medium and high molecular mass polyphenolic compounds in cranberry extracts. The medium molecular mass fraction was enriched with flavonoids and procyanidin dimers whereas procyanidin oligomers (DP > 4) were the dominant class of polyphenols in the high molecular mass fraction. Pre-incubation of Caco-2/15 cells with these cranberry extracts prevented iron/ascorbate-mediated lipid peroxidation and counteracted lipopolysaccharide-mediated inflammation as evidenced by the decrease in pro-inflammatory cytokines (TNF-α and interleukin-6), cyclo-oxygenase-2 and prostaglandin E2. Cranberry polyphenols (CP) fractions limited both nuclear factor κB activation and Nrf2 down-regulation. Consistently, cranberry procyanidins alleviated OxS-dependent mitochondrial dysfunctions as shown by the rise in ATP production and the up-regulation of Bcl-2, as well as the decline of protein expression of cytochrome c and apoptotic-inducing factor. These mitochondrial effects were associated with a significant stimulation of peroxisome-proliferator-activated receptor γ co-activator-1-α, a central inducing factor of mitochondrial biogenesis and transcriptional co-activator of numerous downstream mediators. Finally, cranberry procyanidins forestalled the effect of iron/ascorbate on the protein expression of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2). Our findings provide evidence for the capacity of CP to reduce intestinal OxS and inflammation while improving mitochondrial dysfunction.
Chemical characterization and chemo-protective activity of cranberry phenolic powders in a model cell culture. Response of the antioxidant defenses and regulation of signaling pathways
Oxidative stress and reactive oxygen species (ROS)-mediated cell damage are implicated in various chronic pathologies. Emerging studies show that polyphenols may act by increasing endogenous antioxidant defense potential. Cranberry has one of the highest polyphenol content among commonly consumed fruits. In this study, the hepato-protective activity of a cranberry juice (CJ) and cranberry extract (CE) powders against oxidative stress was screened using HepG2 cells, looking at ROS production, intracellular non-enzymatic and enzymatic antioxidant defenses by reduced glutathione concentration (GSH), glutathione peroxidase (GPx) and glutathione reductase (GR) activity and lipid peroxidation biomarker malondialdehyde (MDA). Involvement of major protein kinase signaling pathways was also evaluated. Both powders in basal conditions did not affect cell viability but decreased ROS production and increased GPx activity, conditions that may place the cells in favorable conditions against oxidative stress. Powder pre-treatment of HepG2 cells for 20 h significantly reduced cell damage induced by 400 μM tert-butylhydroperoxide (t-BOOH) for 2 h. Both powders (5–50 μg/ml) reduced t-BOOH-induced increase of MDA by 20% (CJ) and 25% (CE), and significantly reduced over-activated GPx and GR. CE, with a significantly higher amount of polyphenols than CJ, prevented a reduction in GSH and significantly reduced ROS production. CJ reversed the t-BOOH-induced increase in phospho-c-Jun N-terminal kinase. This study demonstrates that cranberry polyphenols may help protect liver cells against oxidative insult by modulating GSH concentration, ROS and MDA generation, antioxidant enzyme activity and cell signaling pathways.
Cranberry extract suppresses interleukin-8 secretion from stomach cells stimulated by Helicobacter pylori in every clinically separated strain but inhibits growth in part of the strains
It is known that cranberry inhibits the growth of Helicobacter pylori (HP). In human stomach, HP basically induces chronic inflammation by stimulating stomach cells to secrete interleukin (IL)-8 and other inflammatory cytokines, and causes stomach cancer, etc. The aim of this study was to investigate the inhibiting effects of cranberry on HP growth and IL-8 secretion from stomach cells induced by HP, using clinically separated HP strains. HP growth in liquid culture and on-plate culture was evaluated by titration after 2-day incubation and by agar dilution technique, respectively. For IL-8 experiments, MKN-45, a stomach cancer cell line, was incubated with HP for 24 h and IL-8 in the medium was assayed by ELISA. Cranberry suppressed growth of the bacteria only in six of the 27 strains. Meanwhile, it suppressed IL-8 secretion in all the strains. The results may suggest a possible role of cranberry in prevention of stomach cancer by reducing gastric inflammation.
Effects of cranberry powder on biomarkers of oxidative stress and glucose control in db/db mice
Increased oxidative stress in obese diabetes may have causal effects on diabetic complications, including dyslipidemia. Lipopolysccharides (LPS) along with an atherogenic diet have been found to increase oxidative stress and insulin resistance. Cranberry has been recognized as having beneficial effects on diseases related to oxidative stress. Therefore, we employed obese diabetic animals treated with an atherogenic diet and LPS, with the aim of examining the effects of cranberry powder (CP) on diabetic related metabolic conditions, including lipid profiles, serum insulin and glucose, and biomarkers of oxidative stress. Forty C57BL/KsJ-db/db mice were divided into the following five groups: normal diet + saline, atherogenic diet + saline, atherogenic diet + LPS, atherogenic diet + 5% CP + LPS, and atherogenic diet + 10% CP + LPS. Consumption of an atherogenic diet resulted in elevation of serum total cholesterol and atherogenic index (AI) and reduction of high density lipoprotein (HDL)-cholesterol. However, with 10% CP, the increase in mean HDL-cholesterol level was close to that of the group with a normal diet, whereas AI was maintained at a higher level than that of the group with a normal diet. LPS induced elevated serum insulin level was lowered by greater than 60% with CP (P < 0.05), and mean serum glucose level was reduced by approximately 19% with 5% CP (P > 0.05). Mean activity of liver cytosolic glutathione peroxidase was significantly increased by LPS injection, however it was reduced back to the value without LPS when the diet was fortified with 10% CP (P < 0.05). In groups with CP, a reduction in mean levels of serum protein carbonyl tended to occur in a dose dependent manner. Particularly with 10% CP, a reduction of approximately 89% was observed (P > 0.05). Overall results suggest that fortification of the atherogenic diet with CP may have potential health benefits for obese diabetes with high oxidative stress, by modulation of physical conditions, including some biomarkers of oxidative stress.
Cranberries are an important fruit full of polyphenols, anthocyanins, antioxidants, and Nrf2 activators that help to make Ultimate Protector such an outstanding nutritional supplement.
Ultimate 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.
HEALTH BENEFITS OF 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.
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
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
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
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
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.
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.
Strawberries are an important fruit full of polyphenols, anthocyanins, antioxidants, and Nrf2 activators that help to make Ultimate Protector such an outstanding nutritional supplement.