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Monthly Archives: January 2013

  • Acetyl-L-Carnitine Abstracts

    The following is a list of Acetyl-L-Carnitine Abstracts from published scientific research and papers.

    Acetyl-L-Carnitine is available in capsule form from www.integratedhealth.com.

    (REFERENCE 1 OF 13)

    Ido Y McHowat J Chang KC Arrigoni-Martelli E Orfalian Z Kilo C Corr PB Williamson JR

    Neural dysfunction and metabolic imbalances in diabetic rats. Prevention by acetyl-L-carnitine.

    In: Diabetes (1994 Dec) 43(12):1469-77

    The rationale for these experiments is that administration of L-carnitine and/or short-chain acylcarnitines attenuates myocardial dysfunction 1) in hearts from diabetic animals (in which L-carnitine levels are decreased); 2) induced by ischemia-reperfusion in hearts from nondiabetic animals; and 3) in nondiabetic humans with ischemic heart disease. The objective of these studies was to investigate whether imbalances in carnitine metabolism play a role in the pathogenesis of diabetic peripheral neuropathy. The major findings in rats with streptozotocin-induced diabetes of 4-6 weeks duration were that 24-h urinary carnitine excretion was increased approximately twofold and L-carnitine levels were decreased in plasma (46%) and sciatic nerve endoneurium (31%). These changes in carnitine levels/excretion were associated with decreased caudal nerve conduction velocity (10-15%) and sciatic nerve changes in Na(+)-K(+)-ATPase activity (decreased 50%), Mg(2+)-ATPase (decreased 65%), 1,2-diacyl-sn-glycerol (DAG) (decreased 40%), vascular albumin permeation (increased 60%), and blood flow (increased 65%). Treatment with acetyl-L-carnitine normalized plasma and endoneurial L-carnitine levels and prevented all of these metabolic and functional changes except the increased blood flow, which was unaffected, and the reduction in DAG, which decreased another 40%. In conclusion, these observations 1) demonstrate a link between imbalances in carnitine metabolism and several metabolic and functional abnormalities associated with diabetic polyneuropathy and 2) indicate that decreased sciatic nerve endoneurial ATPase activity (ouabain-sensitive and insensitive) in this model of diabetes is associated with decreased DAG.

    (REFERENCE 2 OF 13)

    Herrmann WM Stephan K

    Efficacy and clinical relevance of cognition enhancers.

    In: Alzheimer Dis Assoc Disord (1991) 5 Suppl 1:S7-12

    Changes from the end of 4-week placebo (washout) baselines to the end of 3-month therapy with three chemically different cognition enhancers (CEs) [i.e., piracetam, acetyl-L-carnitine, and nimodipine (NIM)], and parallel changes in placebo controls, were compared to determine the influence of the severity of disease at study entry. Four trials published elsewhere, showing significant treatment differences between active drugs and placebo, were selected according to their (a) sharing at least one global measure for treatment outcome and having shown effects on at least one additional scale or test, and (b) presenting an obvious rank order in the severity of disease. Each study was a standard-controlled clinical phase III trial with greater than 100 psychogeriatric in-or outpatients. The patients' symptoms met the criteria for mild to moderate/severe age-related organic brain syndrome, a core syndrome of senile dementia, either from the primary degenerative, mixed, or multi-infarct type. The extent of changes on placebo was clearly influenced by the mean pretreatment severity of disease. On the whole, the improvements on active drugs reached or exceeded the baseline variability of psychogeriatric scales and tests.

    (REFERENCE 3 OF 13)

    Carta A Calvani M Bravi D Bhuachalla SN

    Acetyl-L-carnitine and Alzheimer's disease: pharmacological considerations beyond the cholinergic sphere.

    In: Ann N Y Acad Sci (1993 Sep 24) 695:324-6

    Since ALCAR and L-carnitine are "shuttles" of long chain fatty acids between the cytosol and the mitochondria to undergo beta-oxidation, they play an essential role in energy production and in clearing toxic accumulations of fatty acids in the mitochondria. ALCAR has been considered of potential use in senile dementia of the Alzheimer type (SDAT) because of its ability to serve as a precursor for acetylcholine. However, pharmacological studies with ALCAR in animals have demonstrated its facility to maximize energy production and promote cellular membrane stability, particularly its ability to restore membranal changes that are age-related. Since recent investigations have implicated abnormal energy processing leading to cell death, and severity-dependent membrane disruption in the pathology of Alzheimer's disease, we speculate that the beneficial effects associated with ALCAR administration in Alzheimer patients are due not only to its cholinergic properties, but also to its ability to support physiological cellular functioning at the mitochondrial level. This hypothetical mechanism of action is discussed with respect to compelling supportive animal studies and recent observations of significant decrease of carnitine acetyltransferase (the catalyst of L-carnitine acylation to acetyl-L-carnitine) in autopsied Alzheimer brains.

    (REFERENCE 4 OF 13)

    Schoemaker JH

    Pharmacological treatment of diabetic peripheral neuropathy:challenges and possibilities.

    In: Br J Clin Pract (1994 Mar-Apr) 48(2):91-6

    Peripheral neuropathy is a well-recognised late complication in both insulin-dependent and non-insulin-dependent diabetes. However, its exact cause remains unknown. Various pathogenic mechanisms have been proposed as an explanation for the development of nerve fibre damage and associated sensory loss in this disease. As a result, many kinds of drugs are currently under evaluation for the treatment of diabetic peripheral neuropathy. This paper describes the rationale behind the usage of all these drugs and reviews major clinical and preclinical results published so far. Supplementary intake of such natural, non-toxic compounds as vitamin constituents, linoleic acid and flavonoids is encouraged, as well as strict control of hyperglycaemia, until the efficacy of one or another experimental drug is established.

    (REFERENCE 5 OF 13)

    Bhuiyan AK Jackson S Turnbull DM Aynsley-Green A Leonard JV Bartlett K

    The measurement of carnitine and acyl-carnitines: application to the investigation of patients with suspected inherited disorders of mitochondrial fatty acid oxidation.

    In: Clin Chim Acta (1992 May 15) 207(3):185-204

    We describe an improved radio-enzymatic method for the measurement of carnitine, short-chain acyl-carnitine and long-chain acyl-carnitine in plasma and tissue. An internal standard, hexadecanoyl-[CH3-3H]-carnitine was synthesised and used to improve the determination of long-chain acyl-carnitine. The between and within batch precisions were 10.4 and 7%, respectively. Control data for neonates, infants, children and adults in the fed and fasted state are documented. In addition we confirm the hypocarnitinaemia associated with pregnancy. Patients with medium-chain acyl-CoA dehydrogenase deficiency were studied during episodes of hypoglycaemia. In both fasted controls and patients there were high concentrations of short-chain acyl-carnitine, however in the latter group there were also low concentrations of free carnitine. We suggest that the monitoring of plasma carnitine and its derivatives is a useful adjunct to the investigation of children suspected to suffer from inherited disorders of mitochondrial beta-oxidation. We also describe a sample preparation procedure suitable for high performance liquid chromatographic analysis of specific acyl-carnitines from urine, plasma and tissue homogenates. The recoveries of acetyl-carnitine, octanoyl-carnitine and hexadecanoyl carnitine from urine were 101.5, 95 and 91% and from plasma 99.5, 91.5 and 85.5%, respectively. Acyl-carnitines (C2-C16) were analysed as their p-bromophenacyl derivatives by reverse-phase high performance liquid chromatography using a ternary gradient of acetonitrile/water/triethylamine phosphate. We report ten patients who excreted octanoyl-carnitine, hexanoyl-carnitine and in some cases a small amount of decanoyl-carnitine. In most of these cases suberylglycine and dicarboxylic acids were also detected by GC/MS. We had access to cultured fibroblasts from five of these patients and were able to demonstrate medium-chain acyl-CoA dehydrogenase deficiency by direct enzyme assay.

    (REFERENCE 6 OF 13)

    De Falco FA D'Angelo E Grimaldi G Scafuro F Sachez F Caruso G

    Effect of the chronic treatment with L-acetylcarnitine in Down's syndrome

    In: Clin Ter (1994 Feb) 144(2):123-7 (Published in Italian)

    Neuropsychologic tests were performed in subjects with Down syndrome in order to assess the effect of a 90-day treatment with L-acetyl-carnitine (LAC). Findings were evaluated statistically (Wilcoxon test) and compared to three further groups of subjects: untreated Down syndrome, mental deficiency due to other cases treated and not treated with LAC (Mann-Whitney U-test). Treated Down syndrome patients showed statistically significant improvements of visual memory and attention both in absolute terms and in comparison with the other groups. No improvement was found in mentally deficient non- Down subjects, so that the favourable effect of LAC appears to be specific for Down patients. In view of the analogies of the pathology and neurochemistry between Down syndrome and Alzheimer degenerative deficiency (deficit of cholinergic transmission) it is suggested that the action of LAC in these pathologies is related to its direct and indirect cholinomimetic effect.

    (REFERENCE 7 OF 13)

    Salvioli G Neri M

    L-acetylcarnitine treatment of mental decline in the elderly.

    In: Drugs Exp Clin Res (1994) 20(4):169-76

    A single-blind clinical trial was carried out on 481 subjects enrolled in 44 geriatric and neurologic units following a strict selection criteria: age, Mini Mental State Examination (MMSE) Global Deterioration Scale and Geriatric Depression Scale (GDS). After the initial screening and enrollment, the trial was run for 150 days in four phases: phase T0 (placebo treatment for 30 days), phases T1 and T2 (L-acetylcarnitine (LAC) 1500 mg/day for 90 days), phase T3 (further 30 days of placebo treatment). Drug efficacy was evaluated according to changes occurring from the beginning to the end of the tests which evaluate either whole and specific cognitive performances, or emotional-affective and relational behaviour. The outcome of phase T3 enabled the authors to estimate the possible favourable effects persisting after termination of L-acetylcarnitine therapy. The cognitive sphere evaluated by MMSE showed a significant increase in the total score at the end of LAC treatment (p < 0.0001). The Randt Memory Test also revealed that LAC treatment improved the items tested: the total score and the memory index increased significantly and the favourable effect persisted after LAC was discontinued. The emotional-affective area showed a significant improvement in the total score of the GDS after LAC therapy, and the positive results were confirmed by the Hamilton Rating Scale (p < 0.0001). The behavioural-relational aspects evaluated by the Family Stress Scale showed a significant decrease in the total score after treatment (p < 0.0004); the same trend was observed in the scores for instability and negative feeling. No significant adverse drug reaction occurred during the trial. In conclusion, the statistical analysis of the data from this single-blind, multicentre trial of mild mental impairment in the elderly showed a significant improvement of several performances during and after LAC treatment. Other reports indicate that this drug may be effective in the treatment of dementia.

    (REFERENCE 8 OF 13)

    Maccari F Arseni A Chiodi P Ramacci MT Angelucci L

    Levels of carnitines in brain and other tissues of rats of different ages: effect of acetyl-L-carnitine administration.

    In: Exp Gerontol (1990) 25(2):127-34

    Male Sprague-Dawley rats, aged 2, 5, 16, 20 and 30 months and normally fed, were used for determination of carnitines in the brain, serum, heart, tibial muscle, liver and urine. With respect to 5-month-old animals, those aged 30 months exhibited a statistically significant decrement of total carnitine levels in the brain, serum, heart and tibial muscle, accompanied by a dramatic increment in the liver. This suggests impaired net transport of carnitines from the liver to the blood in old age. Urinary excretion was similar in the two age groups. One group received from 5 months on daily 75 mg/kg acetyl-L-carnitine in drinking water. At 20 months, the treated animals showed levels of brain, heart and serum carnitines similar to those of 5-month-old animals. The recovery of brain, heart and serum carnitines in the old animals treated with acetyl-L-carnitine indicates that intestinal absorption and tissue uptake remain sufficiently efficient in the course of aging. The lower level of brain lipofuscins due to acetyl-L-carnitine treatment may be related to the effect of the compound on acetylcholine metabolism.

    (REFERENCE 9 OF 13)

    Bella R Biondi R Raffaele R Pennisi G

    Effect of acetyl-L-carnitine on geriatric patients suffering from dysthymic disorders.

    In: Int J Clin Pharmacol Res (1990) 10(6):355-60

    Sixty senile subjects (60-80 years old) with dysthymic disturbances as defined by DSM III (Cat. 390.40) were randomized into two homogeneous groups, one of which was given acetyl-L-carnitine (3 g/day per os) while the other received a placebo. After a washout phase of one week, each patient was evaluated by scoring on the Hamilton Rating Scale for Depression and the Beck Depression Inventory, as well as the Sandoz Clinical Assessment-Geriatric. These tests were administered at the beginning of the trial, prior to drug administration, and repeated during the treatment phase after 30 and 60 days. The results showed that treatment with acetyl-L-carnitine induced a significant reduction, as compared to the placebo (p less than 0.002), in the severity of depressive symptoms and also a significant improvement (p less than 0.0027) in the items measuring the quality of life.

    (REFERENCE 10 OF 13)

    Herrmann WM Dietrich B Hiersemenzel R

    Pharmaco-electroencephalographic and clinical effects of the cholinergic substance--acetyl-L-carnitine--in patients with organic brain syndrome.

    In: Int J Clin Pharmacol Res (1990) 10(1-2):81-4

    In two double-blind, placebo-controlled clinical studies of the nootropic compound acetyl-L-carnitine on the electroencephalogram (EEG) and impaired brain functions of elderly outpatients with mild to moderate cognitive decline of the organic brain syndrome, statistically significant effects could be detected after eight weeks (on the EEG), and after 12 weeks of treatment (on the physician's clinical global impression and the patient-rated level of activities of daily living). Side-effects of acetyl-L-carnitine were generally minor and overall rare. Longer treatment periods and further specifications with regard to the aetiopathology and degree of cognitive impairment are recommended for further clinical studies of this promising compound.

    (REFERENCE 11 OF 13)

    Di Giulio AM Gorio A Bertelli A Mantegazza P Ferraris L Ramacci MT

    Acetyl-L-carnitine prevents substance P loss in the sciatic nerve and lumbar spinal cord of diabetic animals.

    In: Int J Clin Pharmacol Res (1992) 12(5-6):243-6

    Diabetic neuropathy is a disease of peripheral nerves, characterized by axonal atrophy and degeneration that might be preceded by a marked impairment of axonal transport and by a reduced conduction velocity. Sensory nerves are particularly susceptible to diabetes. In the present report it is shown that experimental diabetes in rats causes a significant reduction of the content of the pain-related neuropeptide substance P in sciatic nerve and lumbar spinal cord. Such a loss of substance P is fully prevented by acetyl-L-carnitine treatment. The neuroprotective pharmacological effect is selective and takes place without significant changes of hyperglycaemia and without modifications of the reduced rate of body growth typical of diabetic animals.

    (REFERENCE 12 OF 13)

    Gorio A Di Giulio AM Tenconi B Donadoni L Germani E Bertelli A Mantegazza P Maccari F Ramacci MT

    Peptide alterations in autonomic diabetic neuropathy prevented by acetyl-L-carnitine.

    In: Int J Clin Pharmacol Res (1992) 12(5-6):225-30

    Autonomic neuropathy and gastrointestinal problems are among the most common complications of diabetes. In this report it is shown that a possible correlation between the two disorders might exist, since diabetes causes a profound alteration of the peptidergic innervation of the gut. It is reported that 14 weeks after diabetes induction with alloxan the levels of substance P and methionine-enkephalin are markedly reduced throughout the intestine, while vasoactive intestinal polypeptide content is dramatically increased. Therefore the enteric innervation of diabetic animals is completely disorganized, with some systems undergoing atrophy and others undergoing hypertrophy. Treatment of diabetic animals with acetyl-L-carnitine prevents the onset of the marked peptide changes described above. The results suggest a potential for acetyl-L-carnitine in the treatment of autonomic neuropathies.

    (REFERENCE 13 OF 13)

    Corbucci GG Menichetti A Cogliatti A Nicoli P Arduini A Damonti W Marchionni A Calvani M

    Metabolic aspects of acute cerebral hypoxia during extracoporeal circulation and their modification induced by acetyl-carnitine treatment.

    In: Int J Clin Pharmacol Res (1992) 12(2):89-98

    Following their previous research experiences in human tissue hypoxia, in the present study the authors. investigated the metabolic effects of acute brain hypoxia in a group of patients in course of extracorporeal circulation for aorto-pulmonary bypass. One hundred subjects were treated, half with a placebo and half with acetyl-carnitine to evaluate the effects of oxidative stress in some brain plasmatic metabolites and to verify the effect of acetyl-carnitine on the tissue energy capacity. The levels of lactate, pyruvate, succinate and fumarate showed a significant imbalance due to hypoxia, while the acetyl-carnitine treatment confined the metabolic gradients within physiological limits. This means that during the course of extracorporeal circulation brain hypoxia plays a pathological role assuming the typical picture of cellular oxidative damage and the acetyl-carnitine antagonizes these deleterious effects of hypoxia by a protective mechanism on the energy processes and then on the cellular enzymic activities. In this regard, the d-tyrosine levels, considered as a proteolytic index, confirm the action of acetyl-carnitine on the cell morpho-functional integrity.

  • ULTIMATE PROTECTOR™ AND THE ROLE OF FOUNDATIONAL SUPPLEMENTS FOR HEALTH

    Fred Liers PhDHPDI recently introduced a new type of super antioxidant formula to its lineup of foundational supplements. It is called ULTIMATE PROTECTOR™ — and is already in a class by itself.

    Designed by Dr. Hank Liers for use as both a “standalone” antioxidant formula and as a foundational supplement to be used in conjunction with other foundational supplements, the formula provides shockingly high antioxidant capacity (486,000 ORAC5.0™ units per recommended dose of six capsules).

    In fact, ULTIMATE PROTECTOR™ brings triple action to bear on quenching all five major types of oxidants that damage human health. The formula demonstrates superior free-radical and oxidant quenching capacities (e.g., when compared to other antioxidant-type formulas) because its design provides antioxidant action across a broad spectrum.

    ULTIMATE PROTECTOR™ is unique in that it provides major protection to cells from all of these oxidants: 1) superoxide anion (O2·-), 2) peroxyl radicals (ROO·), 3) hydroxyl radicals (HO·), 4) singlet oxygen (1O2), and 5) peroxynitrite (ONOO-). Most competitor formulas display an uneven response, whereby they may protect well against peroxyl radicals, for example, but poorly or not at all against singlet oxygen. This is the reason ULTIMATE PROTECTOR™ is the leading cell protection formula on the market.

    ULTIMATE PROTECTOR™ ORAC Units Per Serving (six capsules)

    ORAC5.0 Units
    Per Serving*

    Free Radical Type
    17,700 Peroxyl Radical is very important in many biological systems, including lipid peroxidation, DNA cleavage, and protein backbone modification.
    16,500 Hydroxyl is highly reactive and cannot be eliminated by our endogenous enzymes. It damages virtually all types of macromolecules: carbohydrates, nucleic acids, lipids, and amino acids. In the skin, hydroxyl radicals are created by UV exposure.
    6,900 Peroxynitrite is a reactive nitrogen species that is particularly harmful to proteins. It has been implicated in the development of certain cancers, hepatitis, and chronic inflammation. In the skin, peroxynitrite contributes to the breakdown of vital proteins, such as collagen.
    146,000 Singlet Oxygen is generated in the skin by UV exposure. It is linked to the oxidation of LDL cholesterol and cardiovascular disease.
    299,000
    Superoxide Anion is a precursor of all other reactive oxygen species – sometimes referred to as “the mother of free radicals.” It is highly toxic and contributes to lipid and DNA damage.

    486,000

    TOTAL PER DAILY SERVING OF SIX CAPSULES (2.81g)

    * Brunswick Laboratories test results for ORACFN (ORAC5.0™) for ULTIMATE PROTECTOR™ are available here.

    THREE FORMULAS IN ONE

    ULTIMATE PROTECTOR™ can offer such potent free-radical quenching capacity because it combines three formulas into one knockout formula. It supplies potent antioxidants (exogenously) as do some other products like PRO-C™. It also supplies Nrf2 activators that stimulate your body's cells to produce their own antioxidants (endogenously), as do a few Nrf2 products on the market. Finally, it supplies significant amounts of superior-source Vitamin C.

    All three of ULTIMATE PROTECTOR'S modes of antioxidant action are powerful in themselves. But when combined their antioxidant power surpasses all other antioxidant products (including most dedicated Nrf2 activator products) producing a combined ORAC5.0™ value of 486,000 units per recommended serving (six capsules).

    Ultimate Protector - nrf2 activatorULTIMATE PROTECTOR™ works by providing three different types of antioxidant protection, which creates massively potent antioxidant capacity. Here are the three types of sub-formulas included in the product:

    1) POWERFUL ANTIOXIDANTS (from 30 different plant-based ingredients) that when combined produce the highest ORAC5.0™ value ever measured in an antioxidant formula. This combination of many different types of plant antioxidants, including polyphenols, is what makes the product so effective, In fact, if  take thirteen capsules of ULTIMATE PROTECTOR™, you receive 1,053,000 ORAC5.0™ units! As Dr. Mark Sircus writes, "there is no other product that even comes close" to providing this level of antioxidant protection (see his full article here). Moreover, the formula protects against all five major types of free-radicals, and therefore is unique among antioxidant formulas.

    2) NRF2 ACTIVATORS (also from plant-based ingredients) that turn on your cells' own internal antioxidant production systems. The presence of Nrf2 activators in plants often, but not always, coincides with high levels of antioxidants. ULTIMATE PROTECTOR™ leverages plant-based ingredients providing high levels of Nrf2 activators to ensure the production of internal (endogenous) antioxidants in the body. (Note: Internal antioxidant levels cannot be measured by ORAC tests, so higher levels of internally produced antioxidants will provide cell protection above and beyond those capable of measurement by tests, such as ORAC5.0™).

    Consequently, ULTIMATE PROTECTOR™ is a potent Nrf2 activator formula that facilitates the body's production of its own antioxidants, and thereby it is an excellent formula for applications relating to anti-aging, free-radical protection, and optimal health at any age.

    3) VITAMIN C from superior sources. Vitamin C remains the body's most potent water-soluble antioxidant, acts as a generous electron donor; can be “recharged” in the body (when given electrons); and can “recharge” other antioxidants (e.g., Vitamin E) by donating electrons.

    While ULTIMATE PROTECTOR™ is an astonishingly potent standalone antioxidant formula, it will work best when used as part of a complete nutritional supplement program. That is, it is designed to provide the greatest benefits when combined with other HPDI "Foundational Supplements," which include a multivitamin, essential fatty acids, Vitamin C and/or Antioxidant formulas, and Rejuvenate! superfoods.

    PART 2: FOUNDATIONAL SUPPLEMENTS

    HOW ULTIMATE PROTECTOR FITS INTO HPDI'S FOUNDATIONAL SUPPLEMENT SYSTEM

    HPDI designs all of its formulas to be used within a complete nutritional supplementation system based on foundational supplements. While all our supplements can be used individually as standalone formulas, they work best when taken in combination with basic foundational formulas. ULTIMATE PROTECTOR™ is no exception, and in fact, combining its antioxidant protection with a full complement of essential nutrients offers you the greatest potential for creating optimal health and wellness. For example, if you take ULTIMATE PROTECTOR™ with a multivitamin, essential fats, and superfoods like REJUVENATE! Berries & Herbs, then your daily intake of antioxidants will likely measure in the millions of units (as measured by ORAC5.0™).

    FOUNDATIONAL SUPPLEMENTS DEFINED

    Foundational supplements are nutritional supplement formulas we consider essential for optimal health. In our years of experience as supplement designers and nutritional counselors, we at HPDI have found that these four types of formulas taken together are most effective for producing the best results. We have written extensively about the need for establishing and maintaining a daily regimen of foundational supplements (e.g., see "Why You Need Foundational Supplements" and our e-book, The Need for Foundational Supplements (.pdf).

    However, with the arrival of ULTIMATE PROTECTOR™, which is truly a different and groundbreaking formula, we revisit the topic of Foundational Supplements with the intent of introducing it as a foundational supplement and providing a context within which it may best be understood. This will allow you more easily to understand and use ULTIMATE PROTECTOR™ (and the other foundational formulas) to your greatest advantage for creating optimal health.

    Here are the four types of foundational supplements:

    1) MULTIVITAMINS

    2) VITAMIN C or ANTIOXIDANT FORMULAS (including ULTIMATE PROTECTOR™)

    3) ESSENTIAL FATS

    4) HIGH-RNA SUPERFOODS, especially REJUVENATE!™ superfoods

    foundational supplements pyramid

    FIGURE 1. Good health can best be established using four types of foundational supplements: a multivitamin, antioxidants, essential fats, and high-RNA superfoods.

    EVERYONE BENEFITS FROM FOUNDATIONAL SUPPLEMENTS

    Because optimal health depends on the intake of all four types of supplements, we always recommend that everyone take all four of them before taking other types of supplements (i.e., formulas for specific conditions). Foundational formulas are the foundation or “core” of a nutritional supplement program. We start everyone on these in order to build good health. Once basic good health is attained (or someone has at least begun taking all four basic types of foundational formulas), then we advise adding specific supplements for their particular situation and individual needs.

    Supplements taken in addition to foundational supplements can include both “add-on” (i.e., enhancement) formulas (such as magnesium, iodine, vitamin D3, digestive enzymes, etc.) and specific-condition formulas (such as Joint Health Formula, Allergy Support Plus, Intestinal Rejuvenation Formula, Eye & Vision Formula, etc.). The supplements taken after establishing a regimen of foundational supplements will, of course, depend heavily on individual needs, health issues, and priorities.

    As noted, our preference for individuals to take all four foundational supplements does not mean that foundational supplements, “add-on” (or enhancement) formulas, or specific-condition formulas cannot be taken alone. It just means that best results tend to follow use of the complete system of supplementation starting with the four foundational formulas.

    FOUNDATIONAL FORMULAS ARE LIKE THE FOUNDATIONS OF A HOUSE

    Another way of looking at it is that the foundational supplements are like the foundation of a house (i.e., your body and its health, as it were). They are like the bricks or blocks used to establish a base for a dwelling or structure. At this level, it is important that mistakes not be made. If you make a mistake in the foundation of a house, then the structure of the entire house is in danger and any flaw can be significant.

    If you are missing essential components required for health, then your body and its metabolic processes cannot function at their highest level. The foundation must be well established before "building" higher levels. For example, adding additional non-foundational supplements "on top" (so to speak) may not be harmful, but they cannot be used most effectively when the "foundation" below them lacks structural integrity (provided by foundational supplements).

    Once you have established a strong foundation, however, then the “bricks” (i.e., supplements) that come later, such as a supplement for joint health or for vision health, can build upon a strong base. These later supplements will do their jobs effectively when (and because) the foundational “bricks” are laid well. That is, when the foundational “bricks” do their job to ensure the integrity of your entire “house."

    Ultimate Protector - nrf2 activator

    If any one of these foundational “bricks” is weak, damaged, flawed, or inadequate, then the entire structure of the house will lack integrity and be vulnerable to collapse. Similarly, when in your body any of the foundational supplements are missing, or are in low supply, or of poor quality, then the structural integrity of your body and health is at stake.

    FOUNDATIONAL SUPPLEMENTS ARE LIKE AN INSURANCE POLICY

    The health of your entire body depends on your intake of foundational supplements. Therefore, we have developed our nutritional supplements to fit within a  system of supplementation based upon the four foundational supplement types (multivitamin, Vitamin C / antioxidant, essential fats, high-RNA superfoods). It is that simple.

    What is less simple for many people is taking foundational supplements regularly and never missing these basic four. Individuals who understand what foundational supplements offer (and/or who are in touch with themselves enough to feel and know the difference these formulas make in their lives) are usually the same people who exercise the greatest regularity about taking them. Once a person realizes what is possible in terms of improved health with foundational supplements, then taking foundational supplements on a consistent basis becomes a priority, which leads to better results, and improved long-term vitality and health.

    So, these four types of supplements are essentially the basis for good nutrient intake and good health. Of course, these are food supplements. That is, they are used to supplement a good diet. What they provide are a complete group of nutrients needed for health (beyond mere calories). They help guarantee you don't fail to obtain optimal amounts of vitamins, minerals, cofactors, fatty acids, Vitamin C, etc. In this respect they act as a means to ensure you have all the basic building blocks and prevent deficiency. They also are designed to provide optimal amounts of nutrients that you may not easily obtain from foods in the amounts required for best health.

    Take Vitamin C, for example. It is very difficult, if not impossible, to obtain from foods the high levels of Vitamin C often required by the body to support optimal health, quench free radicals, and fight infection. The body, for example, may require thousands of times the US Recommended Daily Intake at certain times. Maintaining relatively high levels of many nutrients is one of the best ways to ensure and protect excellent health.

    THE HPDI LINEUP OF FOUNDATIONAL SUPPLEMENTS

    HPDI offers many different versions of the four basic types of foundational supplements. You can read more about them in greater detail. But here is a brief overview:

    We offer a complete lineup of multivitamins, including vitamins for children (Chewable Kids Mighty-Multi!), an ultra pure formula free of additives (that is suitable for chemically and environmentally sensitive individuals), as well as advanced capsule and tablet forms (Multi Two, Mighty Multi-Vite!).

    We offer several essential fats formulas, including Omega Plus and Essential Fats Plus E. Essential fatty acids play such critical roles in the body that they should be included in any nutritional supplement regimen.

    We offer a wide range of Vitamin C and Antioxidant supplements, including ULTIMATE PROTECTOR™, PRO-C™, OPC-C, and various buffered Vitamin C products in tablet and powder forms. We continue to leverage the unique powers of Vitamin C, including its role as the body's premier water soluble antioxidant, its generosity as an electron/hydrogen donor, its capacity to scavenge and/or reduce a wide range of free radicals (e.g., superoxide, nitroxide, hydroxyl, alkoxyl, and peroxyl radicals), its capacity to react with non-radical species (e.g., singlet oxygen), and its ability to “recycle” other antioxidants (due to its function as an electron donor).

    HPDI is also proud to offer a full line of high-RNA REJUVENATE¡™ super foods, the first superfoods developed to provide high levels of nucleic acids (RNA, DNA), as well as nucleotides and nucleosides. These unique superfoods support optimal body function partly by boosting the production of energy (as ATP) in cells, thereby allowing cells to fulfill their proper functions including metabolism, intercellular communication, and detoxification. When cells can produce larger amounts of energy, the ultimate result is greater energy for the organism (i.e., you!). This manifests as greater physical energy, less fatigue, greater aerobic capacity (easier breathing), greater functional strength, and a more youthful appearance.

    Our REJUVENATE!™ superfoods include Rejuvenate! PLUS (sweet greens), Rejuvenate! Berries & Herbs (advanced cell protection), Rejuvenate! Strawberry-Peach Protein Plus (tasty protein & RNA formula), Rejuvenate! PRO (great taste plus greens), and Rejuvenate! (original greens formula).

     ROLE OF ULTIMATE PROTECTOR™ AMONG FOUNDATIONAL SUPPLEMENTS

    As a foundational supplement, ULTIMATE PROTECTOR™ technically is a Vitamin C / Antioxidant formula within the HPDI system. This means it would be interchangeable with PRO-C™, or any of our Vitamin C products. However, due to the fact that is a super antioxidant formula offering  tens or hundreds times more antioxidant power (capsule for capsule) compared to any of our other Vitamin C formulas, ULTIMATE PROTECTOR™ offers uniquely great potential as a foundational supplement.

    That is, when ULTIMATE PROTECTOR™ is used in combination with a high potency multivitamin, essential fats, and Rejuvenate!™ superfoods, then the total antioxidant potential soars far higher, and the result can be a nutritional supplement program so complete that no essential nutrients are missing. When this happens, the body has what it needs to create health. It also means that antioxidant capacity potentially rises into the millions of ORAC5.0 units daily. At this level, certain markers for aging and oxidation are reduced so dramatically that the aging process (as defined by specific oxidative effects) stops or even reverses itself. This is one of the most amazing benefits of implementing a regimen of high-quality foundational supplements.

    And now, with the introduction of ULTIMATE PROTECTOR™, a base of foundational supplements becomes much more than something to maintain minimum nutrient status for health. Your foundation becomes a rich nutrient base that can dramatically boost energy levels and preserve good health. And this same base can protect you effectively against a host of free radicals and thereby greatly reduce the oxidative processes associated with damaged health, immune breakdown, inflammation, injury, toxic exposures (from radiation to pesticides), and aging itself.

    TRY ULTIMATE PROTECTOR™ FOR YOURSELF...AND EXPERIENCE KNOCKOUT ANTIOXIDANT POWER

    Reports from users include having more energy, less fatigue, less need for sleep (e.g. staying up later and getting up earlier), feeling younger, warding off colds/flu, and generally being more in the "zone." Also, surprisingly, we have received reports from users (and we at HPDI ourselves notice) certain mental effects, including more mental energy, greater ability to focus on tasks, as well as sustained brainpower and increased "mental endurance."

    That an antioxidant formula can provide 486,000 ORAC5.0™ units is quite astonishing. That it's created completely from edible plants individually known as antioxidants and consumed widely is also pretty amazing. But that the formula has the power to help generate and maintain superb health (especially when used with other foundational supplements) is completely awesome. Which is why we developed ULTIMATE PROTECTOR™ in the first place.

    Try ULTIMATE PROTECTOR™ for yourself today, and see just how big a difference it makes in your life. We guarantee it.

    ADDITIONAL RESOURCES

    HPDI website: Why You Need Foundational Supplements

    e-book: The Need for Foundational Supplements (.pdf)

    Rejuvenate!™ Product Comparison Charts

    Dr. Mark Sircus: “Using Vitamin C for Heart Disease, Cancer and Cell Protection”

    Ultimate Protector™ product page

    "Natural Phytochemical Nrf2 Activators for Chemoprevention" – by Dr. Hank Liers

    "Ultimate Protector™: First Impressions" – by Dr. Hank Liers

    "Description and Comparison of ORAC Tests for Well Known Plant Ingredients and ULTIMATE PROTECTOR™" – by Dr. Hank Liers

    "Preventing Free-Radical Damage Using Ultimate Protector™" – by Dr. Hank Liers

    "New Directions for Preventing Free-Radical Damage" – by Dr. Hank Liers

    Ultimate Protector flyer (.pdf)

  • Vitamin D3 – "SUPERSTAR"!

    Dr. Hank Liers, PhDVitamin D3 is emerging into a "SUPERSTAR" of nutrition with more published papers about it than any other vitamin.

    According to PubMed.gov, in 2012 there were 3600 publications with vitamin D in the title or abstract — more than for any other vitamin. This brings the total number of publications on vitamin D listed by PubMed to 33,800. This total compares to 35,100 on vitamin C or ascorbic acid, 21,700 on vitamin E, 19,100 on vitamin A, 17,600 on folate, and 12,000 on vitamin B12.

    Vitamin D thereby has become the most popular vitamin, even though strictly speaking it is not a vitamin. Technically, it is an essential hormone that can be made in the body via the action of ultraviolet B (UVB) light. It can also be obtained orally via diet or supplements.

    THINGS TO KNOW ABOUT THIS SUPERSTAR NUTRIENT

    • In a world of sun avoidance, sun blocks, working indoors, latitudinal effects, etc., nearly the entire population suffers in multiple ways from Vitamin D3 deficiency.

    • Dermatological associations in the US and some other countries have a "zero" sun-exposure policy. This shows how far they lag behind current research. Although Vitamin D supplementation is ideal in winter, in other months, a certain amount of sunshine on skin allows the body to generate its own Vitamin D3 naturally!

    • Inadequate Vitamin D3 is associated with osteoporosis, poor immunity, autoimmune diseases, diabetes, hypertension, cancers, susceptibility to flu, neurological problems, autism, depression, chronic pain, periodontal disease, muscle weakness, birth defects, and other conditions.

    • Human beings optimally produce 10,000–20,000 IU of Vitamin D3 (cholecalciferol) when exposed to full sunlight on a significant portion of skin for about 30 minutes.

    • The body starts to gain the full benefits of Vitamin D3 only after it produces (or intakes orally) about 5,000 IU Daily.

    • Vitamin D3 is a prehormone with powerful effects and with few exceptions cannot be obtained in sufficient amounts from diet.

    • Vitamin D3 can be described as a "superstar" because indirectly it comes from our solar system star...the sun!

    VITAMIN D DEFICIENCY IS EPIDEMIC WORLDWIDE

    Vitamin D deficiency currently is a worldwide epidemic with more than one billion people at risk for diseases associated with low Vitamin D status. Vitamin D is proven safe and effective for a wide range of health conditions (see above and below). There are various reasons for this epidemic, including a significant portion of the world's population living in northerly latitudes (where sunlight is inadequate during many months of the year), sun avoidance, time spent indoors, etc.

    WHAT IS VITAMIN D3 PLUS?

    VITAMIN D3 PLUS is an advanced Vitamin D formula providing high-dose Vitamin D3. Vitamin D3 is the natural form of Vitamin D produced in the body from sunlight and is the form best used for therapeutic purposes.

    One softgel capsule of Vitamin D3 Plus provides 5,000 IU of Vitamin D3 derived from highly purified and molecularly distilled fish liver oils. In addition, the product contains 1,000 IU of Vitamin A also derived from highly purified and molecularly distilled fish liver oils and 10 mcg of Vitamin K2 from menaquinone-7.

    RECOMMENDATIONS FOR SUPPLEMENTING WITH VITAMIN D3 PLUS

    Recent research on Vitamin D suggests that most people will benefit from 5,000 IU of Vitamin D3 daily (unless there is some constraining lifestyle factor or medical reason). Due to its long half-life (about 30 days) in the body, Vitamin D can be taken effectively in smaller doses if needed (e.g., 5,000 IU taken fewer times per week). For example, taking one capsule once per week would give a daily equivalent dose of about 714 IU (i.e., 5,000 IU divided by seven days).

    Additional important nutrients you need to take with Vitamin D3 in order to achieve maximum benefits include magnesium, calcium, zinc, and boron. These additional nutrients are included in our foundational supplements (multivitamins, essential fats, Vitamin C formulas, and Rejuvenate!™ superfoods) and bone formulas (Bone Jour!™and Bone Guardian).

    NUTRITIONAL FACTS REGARDING HPDI'S VITAMIN D3 PLUS 

    The liver and kidney help convert vitamin D to its active hormone form. The major biologic function of Vitamin D is maintaining normal blood levels of calcium and phosphorus. Vitamin D aids in the absorption of calcium, helping to form and maintain strong bones. It promotes bone mineralization in conjunction with a number of other vitamins, minerals (especially magnesium), and hormones. While adequate sun exposure is an ideal means to obtain Vitamin D, most of the population cannot obtain sufficient sunlight during fall and winter months to maintain optimal Vitamin D levels. HPDI's Vitamin D3 Plus offers a solution for keeping Vitamin D levels healthy...so you can be your healthiest!

    When there is insufficient Vitamin D in the body, bones can become thin, brittle, soft, or misshapen. Vitamin D prevents rickets (in children) and osteomalacia (softening of bones) (in adults). These skeletal diseases result in defects that can severely weaken bones. It is estimated that over 25 million adults in the United States either have developed osteoporosis or are at risk of developing it. Osteoporosis is a disease characterized by fragile bones. It results in increased risk of bone fractures. Vitamin D deficiency was recognized as the cause of rickets and osteomalacia 75 years ago. The prevention and cure of these diseases with fish liver oil was a triumph for nutritional science and since then the body’s requirement for Vitamin D has been linked to these conditions. 

    Vitamin D deficiency also has been associated with greater incidence of hip fractures. In older women, a higher Vitamin D intake from diet and supplements is associated with less bone loss. Vitamin D supplementation therefore may help prevent fractures resulting from osteoporosis and the loss of bone. Vitamin D supplements offer a significant means for strengthening bones and skeletal structures, and for preventing bone weakness or bone loss leading to osteomalacia, osteoporosis, and other conditions related to weak bones.

    Vitamin D affects major aspects of human health beyond its classical role in mineral metabolism. It is well established that the active form of Vitamin D acts an effective regulator of cell growth and differentiation in a number of different cell types, including cancer cells. Laboratory, animal, and epidemiologic evidence strongly suggest that Vitamin D may be protective against some cancers. Clinical studies now show Vitamin D deficiency to be associated with four of the most common cancers: breast cancer, prostate cancer, colon cancer, and skin cancer. The active form of Vitamin D plays a critical role in supporting optimal health!

    VITAMIN A AND VITAMIN K2 WORK TOGETHER WITH VITAMIN D

    It is important to understand that Vitamin A works together with Vitamin D and Vitamin K2 to maintain healthy bones. Vitamin D has been shown to prevent Vitamin A toxicity. VITAMIN D3 PLUS includes Vitamin A because Vitamin A and Vitamin D work together to create excellent health!

    Vitamin K2 in the form of MK-7 has been shown in numerous studies to extract calcium from the blood and arteries and deposit calcium into growing or aging bones. In addition, MK-7 appears to have the potential to prevent or even reverse some forms of heart disease and, at the same time, do the same for bone loss. It is believed that patients would be able to be treated with doses of vitamin D that possess greater therapeutic value than those currently being used while avoiding the risk of adverse effects by administering Vitamin D together with Vitamins A and K2. Vitamin D3 Plus includes Vitamin K2 (as MK-7) because MK-7 provides unique benefits for health that complement the benefits offered by Vitamin D...and because they act synergistically to provide other benefits beyond the benefits each provides by itself!

    RECENT RESEARCH STUDIES ON VITAMIN D

    Orthomolecular Medicine News Service recently released the top 16 Vitamin D papers of 2012. These are summarized below.

    4,000 IU vitamin D3 was of great help during pregnancy

    A topic that generated considerable interest this year was the role of vitamin D during pregnancy. In a pair of papers, researchers from the Medical University of South Carolina discussed the findings and implications of their randomized controlled trial of vitamin D supplementation during pregnancy [Hollis et al., 2012; Wagner et al., 2012]. Over 300 women were enrolled in the study. Women were assigned to take supplements containing 400, 2000, or 4000 IU/d vitamin D3 or a placebo. No adverse effects were found such as hypercalcemia or hypercalcuria. This study found that it took 4000 IU/d to raise serum 25-hydroxyvitamin D [25(OH)D] levels to about 40 ng/ml (To convert to nmol/l, multiple ng/ml by 2.5.), a nearly optimal level of 1,25-dihydroxyvitamin D. 1,25-dihydroxyvitamin D is the active or hormonal metabolite of vitamin D which among other things controls the expression of several hundred genes. (See Hossein-nezhad and Holick [2012] for a summary of the effects of vitamin D on fetal development.) In the study, those taking the higher vitamin D doses had significantly reduced risk of primary Cesarean section delivery and pre-eclampsia. Other adverse pregnancy outcomes occur with vitamin D deficiency such as premature delivery and low birth weight, but too few women were enrolled in this study to find statistically significant results on these conditions.

    Mounting evidence that vitamin D deficiency is an important risk factor for autism

    A study from Saudi Arabia examined the relation between serum 25(OH)D level and anti-myelin-associated glycoprotein (anti-MAG) auto-antibodies in autistic children near the age of eight years [Mostafa and Al-Ayadhi, 2012]. There was a very strong inverse relation between the two levels (r = -0.86, p<0.001). The serum 25(OH)D levels in autistic children averaged 19 ng/ml, while that for healthy children averaged 33 ng/ml. Both autistic and healthy children had about six hours of sun exposure per week. The reason that MAG is relevant to autistic children is that MAG is a compound that promotes regeneration of young neurons. Anti-MAG auto-antibodies appear to play a role in some autoimmune disorders relating to neurons through attacking cells that maintain a healthy nervous system. Serum anti-MAG auto-antibodies are strongly related to autism measured with the Childhood Autism Rating Scale. This provides very strong evidence that vitamin D deficiency is associated in some way with autism. Whether increasing serum 25(OH)D levels for those with autism reduces the symptoms of autism remains to be determined.

    Low vitamin D during pregnancy is associated with childhood language impairment

    A study in Perth, Australia measured serum 25(OH)D levels at 18 weeks into pregnancy, and then measured language impairment of the offspring at 5 and 10 years of age. It found that women with serum 25(OH)D levels below 18 ng/ml had children with twice the risk of clinically significant language difficulties compared to those with 25(OH)D levels above 28 ng/ml. Exactly why is not currently known, but there are many possibilities. It is noted that in the United States in the early 2000s, white women of childbearing age had mean 25(OH)D level of 26 ng/ml while black women of childbearing age had mean 25(OH)D level of 14 ng/ml. Both of these levels are low by current standards. As explained below, skin color is directly relevant to serum vitamin D levels produced by exposure to sunlight.

    Higher vitamin D is associated with lower all-cause mortality rates

    A topic of interest at the other end of life was the relation of mortality rate to serum 25(OH)D levels. A meta-analysis of 11 observational studies and 60,000 individuals found a reduction in risk over about 10 years for highest vs. lowest category of 25(OH)D level of mortality of 29% [Zittermann et al., 2012]. Comparing graded levels of intake, the reduction in risk was 14% for an increase of 5 ng/ml, 23% for an increase of 10 ng/ml, and 39% for an increase of 20 ng/ml in plasma levels of 25(OH)D, starting from a median of ~11 ng/ml. The participants starting with the lowest levels of serum 25(OH)D received the greatest benefits. Those who started with higher serum levels, closer to optimal (30-40 ng/ml), received less benefit from additional vitamin D. This relation between starting serum 25(OH)D levels and health outcome is not surprising because it is similar to many other health studies. Since 25(OH)D levels likely changed over the duration of the studies, and some participants died of unrelated causes, the actual effect of serum 25(OH)D level on mortality rate is greater than these estimates.

    And less cardiovascular disease

    Cardiovascular disease is an important contributor to mortality rates. A study of 11,000 patients in Kansas was reported. The patients had a mean age of 58±15 years, a body mass index of 30±8 kg/m2, and a mean serum 25(OH)D level of 24±14 ng/ml [Vacek et al., 2012]. Serum 25(OH)D levels below 30 ng/ml was significantly associated with several cardiovascular-related diseases, including hypertension, coronary artery disease, cardiomyopathy, and diabetes. After a period of 5.5 years, those with serum 25(OH)D levels below 30 ng/ml had twice the mortality rate of those with higher 25(OH)D levels.

    And less risk of diabetes mellitus type 2

    In a 2.7-year study of 2000 prediabetics, participants with the highest third of 25(OH)D levels (median, 30.1 ng/ml) had a reduction in risk of 28% for developing diabetes mellitus type 2 compared with participants in the lowest third (median, 12.8 ng/ml) [Pittas, 2012].

    . . . and less diabetes mellitus type 1 (T1DM)

    An observational study on insulin-dependent diabetes mellitus (T1DM) was based on 1000 U.S. military service personnel who developed this disease between 2002 and 2011 [Gorham et al., 2012]. They had provided blood samples between one and ten years prior to developing T1DM. They were carefully matched with another thousand service personnel who did not develop T1DM. There was a reduction in risk of 78% for developing T1DM for those with serum 25(OH)D levels above 24 ng/ml compared to those with levels above 24 ng/ml. This finding is highly statistically significant and is one of the strongest studies of its type.

    Fewer bacterial and viral infections

    The effect of vitamin D in reducing risk of infections is a topic of increasing interest. Vitamin D reduces risk of infections primarily by strengthening the innate immune system, primarily by inducing production of cathelicidin, a polypeptide with antimicrobial and antiendotoxin properties. It also shifts production of cytokines, a type of cell signaling molecule, away from proinflammatory ones, and has a number of other actions on both the innate and adaptive immune system [Lang et al., 2012]. While the effects of vitamin D have been found mostly for bacterial infections, some have also been reported for viral infections such as influenza, HIV, and hepatitis C [Lang et al., 2012]. In a supplementation study in Sweden involving 140 patients with frequent respiratory tract infections (RTIs) using 4000 IU/d vitamin D3, those in the supplementation group increased their serum 25(OH)D level to 53 ng/ml while those in the placebo group had levels near 27 ng/ml [Bergman et al., 2012]. Those taking vitamin D3 had a 23% reduction in RTIs and a 50% reduction in the number of days using antibiotics.

    The benefits of vitamin D in reducing risk of cancer

    One of the important and well-documented effects of vitamin D is reduced risk of cancer and increased survival after cancer diagnosis. There were 400 publications on vitamin D and cancer in 2012 according to PubMed.gov. Evidence from ecological, observational and laboratory studies have identified over 15 types of cancer for which higher solar UVB light and/or serum 25(OH)D levels are associated with reduced risk. Two of the papers are especially noteworthy. One, a study from Norway involving 658 patients with either breast, colon, lung, or lymphoma with serum 25(OH)D levels determined within 90 days of cancer diagnosis were followed for up to nine years [Tretli et al., 2012]. Compared to those with levels <18 ng/ml, those who originally had levels >32 ng/ml had a reduction in risk for dying from cancer of 66%. To a cancer patient, this would be a lifeline.

    Another cancer paper reported the results of supplementation with 4000 IU/d vitamin D3 of those with low-grade biopsy-assayed prostate cancer [Marshall et al., 2012]. Forty four patients successfully completed the one-year study. Twenty four of the subjects (55%) showed a decrease in the amount of cancer; five subjects (11%) showed no change; 15 subjects (34%) showed an increase. In comparison, with a historical group of 19 patients, only 4 (21%) had reductions in the amount of cancer, 3 (16%) showed no changes, and 12 (63%) showed an increase in cancer. Thus optimal vitamin D supplementation appears to be useful for treating those with cancer.

    Falls and fractures

    The classical role of vitamin D is to regulate calcium and phosphate absorption and metabolism, leading to strong bones. A pooled analysis of 31,000 persons (mean age, 76 years; 91% women) participating in randomized controlled trials of vitamin D supplementation who developed ~1000 incident hip fractures and ~3800 nonvertebral fractures found that those with the highest intake (median 800 IU/d; range 792-2000) had a 30% reduction in risk of hip fracture and a 14% reduced risk of nonvertebral fracture [Bischoff-Ferrari et al., 2012]. The role of vitamin D in neuromuscular control also plays an important role in reducing risk of falls and fractures.

    Skin pigment adapts slowly to changed ultraviolet environment

    Jablonski and Chaplin have published a series of papers on human skin pigmentation and its relation to solar ultraviolet radiation (UVR) [Jablonski and Chaplin, 2012]. Their primary thesis is that human skin pigmentation has adapted to UVR conditions where a group of people live for 50 generations, or about a thousand years. UVR from mid-day sunlight produces vitamin D, which provides important protection against many diseases, but sunlight also causes skin cancer and destruction of folate. Dark skin protects against free radical production, damage to DNA, cancer, and loss of folate. Thus, dark skin is best in the tropical planes regions while pale skin is best at high latitude regions. Those with skin adapted to UVB between 23° and 46° have the ability to tan, which is an adaptation to seasonal changes in solar UVB doses. However, in recent times, people have moved or traveled to regions where their skin pigmentation is not suited to the local UVR conditions. They discuss three examples: nutritional rickets, multiple sclerosis and melanoma. Their abstract concludes with this observation: "Low UVB levels and vitamin D deficiencies produced by changes in location and lifestyle pose some of the most serious disease risks of the twenty-first century."

    Vitamin D levels for traditionally living Africans

    A study on traditionally living Africans near the equator provides information on "normal" 25(OH)D levels. A paper was published on serum 25(OH)D levels of the Masai and the Hadzabe living near 4° S in Tanzania [Luxwolda et al., 2012]. They have skin type VI (very dark), wear a moderate amount of clothing, spend the major part of the day outdoors, but avoid direct exposure to sunlight when possible. The mean serum 25(OH)D levels of Maasai and Hadzabe were 48 (range 23-67) ng/ml and 44 (range 28-68) ng/ml, respectively. This finding suggests that serum 25(OH)D levels in the range of 40-50 ng/ml may be optimal for human health, which is generally consistent with observational studies for a number of health outcomes.

    Vitamin D is made by exposure to sunlight to a significant degree only when the sun is 45 degrees or more above the horizon. At the latitudes of North America and Europe, this is summer midday sunlight between the hours of 11 a.m. and 3 p.m. In the early morning or late afternoon, light-skinned individuals may tan but they hardly get any vitamin D from sunlight. And in the winter, nobody gets much vitamin D from the sun. This explains the health benefits of taking supplements of vitamin D.

  • Description and Comparison of ORAC Tests for Well Known Plant Ingredients and Ultimate Protector™

    Hank Liers ORAC testsThe term "ORAC" (standing for “Oxygen Radical Absorption Capacity”) describes a test developed by Brunswick Labs as an analytical tool for estimating the antioxidant capacity of substances. The measurement of ORAC value involves an in vitro test of the capacity of a substance to trap peroxyl radicals. Brunswick Labs remains a leader in the development of ORAC tests.

    The development of the ORAC test was an important advancement in commercially available analysis of the capacity of various foods and ingredients to trap the peroxyl radical. It has become a de facto standard in the natural products industry. However, the original ORAC method was considered to be just a starting point for comprehensive antioxidant analysis.

    The arrival of more comprehensive ORAC tests like Brunswick Labs' ORAC5.0™ test (also known as ORAC-FN) measuring the antioxidant capacities of five different types of oxidants allows more accurately determination of the total antioxidant quenching power of substances. This helps to better assess the effectiveness of existing antioxidant formulas, and supports development of improved formulas that provide a broad range of antioxidant foods and nutrients that combat all major types of free radicals.

    Ultimate Protector - nrf2 activator

    FIVE TYPES OF FREE RADICALS AND OXIDANTS

    Peroxyl, Hydroxyl, Peroxynitrite, Superoxide Anion, Singlet Oxygen

    The fact is that there are a variety of “free radicals” that operate in humans — the most important of which are the primary radicals peroxyl, hydroxy peroxynitrite, superoxide anion, and singlet oxygen. Brunswick Labs has reported that even though the peroxyl radical is the major free radical in the body, it represents no more than 27% of the total antioxidant potential of selected fruits and vegetables. In addition, the original ORAC method favors certain antioxidant substances over others (e.g., anthocyanins over carotenoids) due to the use of a single free radical source (i.e., the peroxyl radical).

    Various free radicals are formed, behave, and are defended against differently. They all contribute to 1) a general condition called “oxidative stress,” or cellular damage and 2) broad human health concerns caused, for example, by inflammation, DNA and protein damage. They are each implicated in different health problems — from cardiovascular disease to macular degeneration and Alzheimer’s disease and to skin damage and aging. We provide a brief summary of these free radicals (below).

    The Peroxyl Radical is very important in many biological systems, including lipid peroxidation, DNA cleavage, and protein backbone modification. Hydroxyl is highly reactive and cannot be eliminated by our endogenous enzymes (such as SOD and glutathione). It can damage virtually all types of macromolecules: carbohydrates, nucleic acids, lipids, and amino acids. In the skin, hydroxyl radicals are created by UV exposure. Peroxynitrite is a reactive nitrogen species that is particularly harmful to proteins. It has been implicated in the development of certain cancers, hepatitis, and chronic inflammation. In the skin, peroxynitrite contributes to the breakdown of vital proteins, such as collagen.

    Superoxide Anion is a precursor of all other reactive oxygen species and sometimes is referred to as “the mother of free radicals.” It is highly toxic and contributes to lipid and DNA damage. Antioxidants that scavenge superoxide anion also help prevent the formation of radicals such as hydrogen peroxide and hydroxyl. Superoxide anion has been linked to hypertension and cardiovascular damage. Singlet Oxygen is generated in the skin by by UV. In vivo, it is linked to the oxidation of LDL cholesterol and cardiovascular disease. Singlet oxygen is highly unstable and durable. Carotenoids are very effective at scavenging singlet oxygen.

    The importance of an ORAC test that measures the effectiveness of antioxidant foods, phytochemicals (e.g., polyphenols), vitamins, and other food-based substances against a broader range of free radicals (i.e., beyond the peroxyl radical) becomes apparent when considering how these antioxidants operate in the body. The body faces a diverse group of oxidants, so any test that can provide an estimate of how well a given set of antioxidants will protect cells in reality will also provide a distinct advantage for designing superior antioxidant formulas.

    A NEW, MORE COMPREHENSIVE ORAC TEST: ORAC5.0™

    Brunswick Labs recently introduced a new, more comprehensive form of ORAC test called ORAC5.0™ (also known as ORAC-FN). This test expands the ORAC platform to measure the antioxidant capacity against each of the five primary reactive oxygen species mentioned above. ORAC5.0™ substantially improves broad-spectrum antioxidant analysis and gives evidence of the diverse antioxidant potential of natural products against radicals other than just the peroxyl radical. Brunswick Labs’ research shows that the antioxidants found in a wide range of natural products are effective against these primary radicals, and that in many cases a preponderance of a product’s antioxidant capacity is described by performance against the four new radicals added to the new ORAC5.0™ panel (which is now the king of ORAC tests).

    Table 1.0 (below) shows ORAC5.0™ test results for a range of natural substances known to have significant health benefits and that are broadly used in nutritional supplements. In general, these substances are included at mg levels in supplement formulas. For example, maximum per serving amounts are about 20 mg for astaxanthin, 400 mg for bilberry 25%, 100 mg for grape seed/fruit, 200 mg for green tea extract, 200 mg for coffee berry extract, 100 mg for pine bark, and 100 mg for resveratrol. Considering this the number of total ORAC5.0™ units consumed per serving would typically be in the range of 1,000 to 30,000. Also, it is important to observe that with the exception of green tea extracts none of these ingredients gives excellent protection from the peroxynitrite radical and even green tea extract at the level of 200 mg daily only gives a peroxynitrite radical ORAC value of 400 units.

    ULTIMATE PROTECTOR™ DEMONSTRATES HIGH ORAC5.0™ VALUE

    In the table, we have also included the results for HPDI’s new ULTIMATE PROTECTOR™ cell protection formula. It can be seen that ULTIMATE PROTECTOR™ has a total ORAC5.0™ value that is more than 50% greater than green tea extract and many times greater than most of the other ingredients. Table 2.0 shows the total ORAC5.0™ units per daily serving. Because the daily recommended serving for ULTIMATE PROTECTOR™ is 2.8 grams (six small capsules), the total daily ORAC5.0™ measures 486,000 units! This value is over 10 times greater than you receive from typical serving sizes of the ingredients shown in the table!! In addition, ULTIMATE PROTECTOR™ provides excellent protection against all five of the free radical types in the body — something none of the specific ingredients do well!!

    Table 1.0 ORAC5.0™ Comparative Results

    Ingredient Peroxyl Radical Hydroxyl Radical Peroxy-nitrite Radical Super-
    oxide Radical
    Singlet O2 Radical Total ORAC5.0
    Astaxanthin - - - 1,000 9,000 10,000
    Bilberry 25% 7,000 25,000 1,000 16,000 5,000 54,000
    Cocoa 10,000 28,000 1,000 11,000 2,000 52,000
    Grape Seed/Fruit 17,000 47,000 1,000 25,000 4,000 94,000
    Green Tea 11,000 41,000 2,000 56,000 3,000 113,000
    Coffee Berry 5,000 29,000 1,000 1,000 2,000 38,000
    Mangosteen 4,000 8,000 1,000 18,000 4,000 35,000
    Pine Bark 7,000 23,000 1,000 17,000 2,000 50,000
    Resveratrol 12,000 50,000 1,000 8,000 22,000 93,000
    ULTIMATE PROTECTOR 6,300 5,900 2,500 106,000 52,000 173,000
    Results are expressed in micro mole TE/g

    Table 2.0 ULTIMATE PROTECTOR™ ORAC Units Per Serving

    ORAC5.0 Units Per Serving* Free Radical Type
    17,700 Peroxyl Radical is very important in many biological systems, including lipid peroxidation, DNA cleavage, and protein backbone modification.
    16,500 Hydroxyl is highly reactive and cannot be eliminated by our endogenous enzymes. It damages virtually all types of macromolecules: carbohydrates, nucleic acids, lipids, and amino acids. In the skin, hydroxyl radicals are created by UV exposure.
    6,900 Peroxynitrite is a reactive nitrogen species that is particularly harmful to proteins. It has been implicated in the development of certain cancers, hepatitis, and chronic inflammation. In the skin, peroxynitrite contributes to the breakdown of vital proteins, such
    as collagen.
    146,000 Singlet Oxygen is generated in the skin by UV exposure. It is linked to the oxidation of LDL cholesterol and cardiovascular disease.
    299,000 Superoxide Anion is a precursor of all other reactive oxygen species – sometimes referred to as “the mother of free radicals.” It is highly toxic and contributes to lipid and DNA damage.
    486,000 Total Per Daily Serving of Six Capsules (2.81g)

    Review the Brunswick Labs Ultimate Protector™ ORAC5.0™ Test Report Here

    ADDITIONAL RESOURCES

     Questions & Answers about Ultimate Protector

    The Amazing Healing Potential of Natural Nrf2 Activators

    Ultimate Protector™ and the Role of Foundational Supplements for Health

    New Directions For Preventing Free-Radical Damage

    Natural Phytochemical Nrf2 Activators for Chemoprevention

    Ultimate Protector™ Brunswick Labs ORAC5.0™ Test Results

    Description and Comparison of ORAC Tests for Well Known Plant Ingredients and Ultimate Protector™

    Ultimate Protector™: First Impressions

    Ultimate Protector™ ORAC5.0™ Test Results

    Preventing Free-Radical Damage Using Ultimate Protector™

    New Directions for Preventing Free-Radical Damage

    Natural Phytochemical Nrf2 Activators for Chemoprevention

    Ultimate Protector flyer (.pdf)

  • Celiac Disease and Gluten Sensitivity: Supplements and Activity Schedule

    Fred Liers PhDCeliac disease (also known as "sprue") is an autoimmune disorder of the small intestine. It is characterized by sensitivities and reactions to wheat gluten found in wheat and wheat subspecies (spelt, semolina, durum), as well as to similar proteins found in other common grains (including barley and rye).

    In celiac disease, exposure to gluten creates an autoimmune reaction that leads to inflammation in the small intestine. This ultimately leads to erosion or wearing down of the villi lining the small intestine (known as villous atrophy).

    Villi absorb nutrients from foods. Therefore, a major problem in celiac disease is malabsorption. Adverse changes in the bowel decrease its ability to absorb macronutrients (carbohydrates and fats), minerals, and important fat-soluble vitamins (A, D, E, and K). Many health conditions can result from malabsorption depending on the nutrients in which the body becomes deficient.

    Symptoms vary widely, but typical health effects include fatigue, chronic diarhrrea, anemia, abdominal pain (as well as distension and bloating), lactose intolerance, malabsorption, villous atrophy, failure to thrive (in children), and other adverse effects.

    In addition, celiac disease has been linked with various other conditions, including malnutrition, autoimmune disorders, dermatitis, growth delay, infertility, abnormal liver function, colitis, irritable bowel syndrome (IBS), diabetes type 1, nerve damage, motor disturbances, mental disorders (e.g., schizophrenia), autism, as well as ulcers, stricture, and increased risk for cancers of the small intestine.

    The generally recommended solution for individuals suffering from celiac disease is a gluten-free diet.

    GLUTEN SENSITIVITY

    Celiac disease is basically gluten intolerance. Gluten sensitivity is different in that it may not manifest as complete intolerance (like celiac disease), but nevertheless result in some similar symptoms: digestive problems, bloating, inflammation, allergic-type responses, poor digestion, etc. Similar symptoms may also result from allergy to wheat. However, like celiac disease, the generally recommended solution for gluten sensitive individuals is a gluten-free diet.

    SOLUTIONS

    Consuming a gluten-free diet is critically important for individuals suffering from celiac disease, gluten sensitivity, and wheat allergy. In addition to diet, however, there are many other practices that can contribute to greater overall health. These practices can strengthen the body and the immune system, and create a more robust digestive tract.

    In addition to a gluten-free diet, practices we recommend for individuals suffering from celiac disease, gluten sensitivity, and/or wheat allergy include:

    1) Daily or regular use of foundational supplements. Foundational supplements include a high-potency multivitamin, a Vitamin C / antioxidant formula (like PRO-C or Ultimate Protector™), essential fats, and a high-RNA superfood like Rejuvenate!™.

    Some of HPDI's recommended foundational supplements:

    a) Mighty Multi-Vite!™ – complete, high potency multivitamin

    b) Essential Fats Plus E – complete essential fats formula with balanced omega-3 and omega-6 plus astaxanthin and mixed tocotrienols.

    c) Ultimate Protector™ – our newest and most powerful antioxidant formula (486,000 ORAC5.0™ units per recommended serving!). This unprecedentedly powerful formula provides plant-based antioxidants and Nrf2 activators, as well as superior source Vitamin C.

    d) Rejuvenate!™ Plus – or another Rejuvenate! superfood. See all five Rejuvenate superfoods on our Rejuvenate! comparison page.

    You can read more about the need for foundational supplements here: (http://www.integratedhealth.com/foundational-supplements/foundational-supplements.html/)

    2) Additional “condition specific” supplements known to benefit individuals with celiac disease and/or gluten sensitivity. These include Intestinal Rejuvenation Formula and Bone Jour!™. Other helpful supplements include Nascent Iodine, Prescript-Assist® (probiotic), Prolyt (proteolytic enzyme), and Digase (digestive enzymes).

    A few of the most important specific condition formulas for Celiac Disease:

    • Intestinal Rejuvenation Formula – a unique clearing and rejuvenating formula for the entire gastrointestinal tract

    • Digase: Plant-based enzymes for helping digestion and digestive health

    • Prescript-Assist®: A full-spectrum probiotic formula

    2) Dietary practices that emphasize variety, purity, and alkaline-forming foods. A varied diet high in plant foods is also a diet that tends to be alkaline forming. An alkaline forming diet boosts oxygenation of tissues, reduces inflammation in tissues, and generally includes more fiber, which is necessary for good gastrointestinal health.

    3) Exercise. Exercise helps all aspects of human physiology. It is especially important in the context of Celiac Disease (and other gastrointestinal problems) because it helps move the intestines, thereby helping elimination functions. Exercise also boosts blood circulation and movement of lymph fluid necessary for detoxification.

    Exercise need not be overwhelming or difficult. Start with shorter periods of less intense exercise, and then gradually increase intensity and/or duration. Walking, hiking, cycling, swimming, and yoga are some good types of exercise, all of which can be done at your own pace and level of comfort. Set a schedule and stick to it. Consistency is key.

    4) Stress Reduction Techniques. Regular practices such as daily meditation, tai chi, qigong, prayer, walks in nature, etc. are proven to reduce stress and help balance mind and body. A well balanced mind-body system is known to improve digestion and support gastrointestinal health.

    SUPPLEMENT SCHEDULE

    Description AM Noon PM Comments
    PRO-C™ or
    Ultimate Protector™
    1–2 caps 1–2 caps 1–2 caps Take with meals. Start with 1 capsule three times daily and gradually increase to 2 caps three times daily.
    Essential Fats Plus E 1 softgel 1 softgel 1 softgel Take with meals
    Mighty Multi-Vite! 2 caps 2 caps Take with meals
    Rejuvenate!™ Strawberry-Peach Protein Plus 1–2 scoops  1 scoop Take as meal replacement or snack. Start slowly and slowly increase to full dosage.
    Intestinal Rejuvenation Formula 1 tsp 1 tsp 1 tsp Start with 1 teaspoon daily. Gradually increase to 1 or more tablespoons daily.
    Bone Jour! – contains calcium, magnesium, and other minerals 3 caps 3 caps Take with meals

    As noted, other useful supplements include Nascent Iodine 2% (10 drops daily on an empty stomach), Digase digestive enzymes (2 capsules with each meal), Prolyt (2 capsules with each meal), Prescript-Assist® (1–2 caps daily), sublingual Vitamin B12 as methylcobalamin (5 mg daily), Hematin iron supplement (1 tablet daily), and Double Zinc Plus (1 tablet daily).

    MORE ON DIET, ETC.

    Consume a diet that includes zero gluten containing grains (organic brown rice, wild rice, organic corn, and quinoa are okay). Eat free-range organic meat, organic poultry and deep sea fish and foods high in fiber such as organic vegetables, fruits, beans, nuts and seeds (sunflower, flax, chia, pumpkin, walnut, almond, and sesame in small amounts — one or two ounces daily — are beneficial). Try eating Hank's Vegetable Soup several times per week. Eat several servings of fresh berries (blueberries, strawberries, raspberries, cranberries, etc.) on a daily basis.  Avoid over consuming sweets (sugar) and processed/refined foods.

    Try not to eat the same thing every day. Symptoms can be caused by allergic reactions to the food you eat.  Be observant to correlations between symptoms and the foods you have eaten. Also, avoid genetically modified foods (GMOs) whenever possible, as there is a connection between GMO consumption and health issues, including leaky gut syndrome and other gastrointestinal problems.

    Again, as noted, be sure you get adequate low-impact exercise on a daily basis.  This could include walking up to four miles a day, yoga, swimming, or bicycling. Take warm baths daily with baking soda (one cup) and Ancient Minerals magnesium chloride flakes (two cups).

    Celiac disease and gluten sensitivity, like other conditions, can be avoided or mitigated with a proper program of diet, supplements, exercise, stress reduction, and other effective health-building practices.

  • Review of Scientific Research on Oligomeric Proanthcyanidins (OPC)

    Dr. Hank Liers, PhD1.0 INTRODUCTION

    Research on oligomeric proanthocyanidins (OPC) has been ongoing in US, Europe and elsewhere for the past 40 years. The results of this research are very exciting, especially the results of the research on plant extracts including those obtained from pine bark, grape seeds, and whole grape (seed, skin, and stem).

    I became involved with the scientific research data on OPC starting in 1989 and designed my first product called PYC-C (standing for pycnogenols and Vitamin C) that same year. It was one of the first products in the US that used pine bark OPC. At that time, the price for the pine bark extract was $4,000/kg.

    In late 1989, I went to a conference on pine bark extract held in France, and I actually visited the pine forest facility where the bark was processed. About a year later, I learned about the availability of grape seed extract which cost less than half the price of pine bark extract and appeared to contain a greater amount of OPC.

    During the last 24 years I have designed more than 20 products incorporating OPC from whole grape and grape seed extracts. Some of these products include: Antioxidant Formula, Diabetes Support FormulaEye & Vision FormulaJoint Health FormulaChewable Kid's Mighty-MultiHank & Brian's Mighty Multi-vite!Mini MultiMulti TwoOPC-CPRO-CProlyt, Rejuvenate! Pro, Rejuvenate! Berries & Herbs, and Rejuvenate! Strawberry-Peach Protein Plus.

    In 1993, I completed a review of the basic science behind OPC that included most of the research of Jack Masquelier the pioneer behind much of the discoveries in this field of research. Around this time scientific articles on OPC began to appear in well known magazines. For example, Morton Walker published articles on this subject in both Raum & Zeit1 and The Townsend Newsletter for Doctors2.

    The purpose of this article is to provide details on both the laboratory and clinical research findings concerning these materials. Historically the research literature has used terms such as leucocyanidins, pycnogenols, procyanidins, oligomeric proanthocyanidins, and others to refer to the plant materials which are extracted by a process patented4 by Jack Masquelier about 40 years ago and which has a unique signature when subjected to a test developed by Bate-Smith5.

    2.0 BACKGROUND

    Before delving deeply into the research findings, I will provide a little background on the structure of bioflavonoids.

    One way of looking at the bioflavonoids is that they are two ring structures (A & B) connected by a three carbon chain (C). Figure 1 shows the general structure of bioflavonoids. The main classes which are distinguished by the types of molecules found at the different numbered positions are FLAVONOL (yellow), ISOFLAVONOL, FLAVONE (yellow), FLAVONONE (colorless), ISOFLAVONONE, ISOFLAVONE (colorless), ANTHOCYANDIN (red, blue, violet), CHALCHONE, and CATECHIN (colorless).

    Those classes beginning with the "iso" prefix refer to the structures in which the "B" ring is flipped down from the 2 position to the 3 position. For the anthocyanidins and the catechins the "C" ring is considered to be open which accounts for their greater water solubility. The catechins which are in the class termed flavon-3 ols have an "OH" molecule at the 3, 5, and 7 positions. Depending upon the orientation of the "OH" molecule in the 3 position the material is called catechin (C) or epicatechin (E). In the diagrams these are distinguished by arrows and dashed lines.

    pycfig1
    Figure 1 — General Structure of Bioflavonoids

    The catechins (referring to both catechins and epicatechins) have the peculiar property of forming polymers with themselves. When the number of connected catechins is 10 or less they are called oligomers and thus the term used is "oligomeric proanthocyanidins." When the number of connected catechins is more than 10 the term condensed tannins is generally used. The term proanthocyanidins comes about because when these materials are subjected to 10% hydrochloric acid and heated to boiling (this is what is termed the Bate-Smith test5), they yield an anthocyanidin, with its intense red coloration, and a catechin.

    Figure 2 shows a dimeric proanthocyanidin which consists of catechin on top and epicatechin on the bottom. Depending upon which molecule of the lower "A" ring attaches to the "4" position of the upper "C" ring, there are different series of these dimers. The one shown in the diagram fits into what is called the "B" series and is the one of most interest to us here. The dimeric "B" series itself has four members depending whether and where there are catechins and epicatechins, e.g., E-E, C-E, E-C, and C-C. Each of these have been synthesized and studied in the laboratory and have somewhat different chemical properties.

    It took almost 20 years for the researchers to come to this understanding concerning the dimers. The situation with respect to trimers, tetramers, pentamers, etc. gets extremely complex and, therefore, much of the research has concentrated upon the dimers or upon materials in which the dimers are the main constituent. This background is sufficient for the reader to understand the bulk of the research results.

    pycfig2

    Figure 2 — Structure of a Dimeric Proanthocyanidin

    3.0 THE EXTRACTION PROCESS

    In 1969, Jack Masquelier was granted US Patent No. 3,436,407 regarding the process by which the oligomeric proanthocyanidins could be extracted from raw plant materials in general and pine bark in particular. A flow diagram of the process is shown in Figure 3. The steps of this process insure that the materials obtained are highly water soluble, do not contain condensed tannins, and are not contaminated with toxic substances such as heavy metals, pesticides, and residual solvents.

    The proanthocyanidins content of the extracted material is quantitatively assessed by using their property of having a strong affinity for collagen -- no other component of the extract having a strong affinity for collagen. In this assessment, a solution of known titre of the extract is prepared and brought in contact with hide powder (collagen). The amount of proanthocyanidins fixed to the hide powder is determined by filtration and weighing, which gives a measure of the original content of the proanthocyanidins in the extract.

    The material obtained from pine bark by this process is an astringent tasting light beige powder which can be kept indefinitely in a dry bottle at room temperature. When subjected to high pressure liquid chromatography (HPLC) the constituents shown in Table 1 are typically identified.

    • 1. GALIC ACID – 3.2%

    • 2. DIMERS (Catechin and Epicatechin) – 40.9%

    • 3. CATECHIN – 18.9%

    • 4. PIC X – 12.8%

    • 5. CAFEIC ACID – 1.9%

    • 6. EPICATECHIN – 0.2%

    • 7. COUMARIC ACID – 0.2%

    • 8. TAXIFOLIOL – 2.1%

    • 9. FERULIC ACID – 0.5%

    • 10. OTHER including Trimers, Tetramers – ~19%

    Table 1. Representative Constituents and Percentages of Pine Bark Extract as Determined by HPLC Analysis

    It can be seen from the analysis that the dimeric proanthocyanidins are by far the major component in pine bark extract with a significant amount of the catechin monomer and of other constituents identified to be mostly trimeric and tetrameric proanthocyanidins. Gallic acid, cafeic acid, and ferulic acid are known to have potent in vitro anti-bacterial and anti-viral properties7.

    Research investigations8,9,10 have discovered that oligomeric proanthocyanidins (OPC) may be found in a wide range of other plants materials including:

    • CRAB APPLE

    • APPLE

    • MOUNTAIN CRANBERRY

    • AVOCADO PEAR STONE

    • UNRIPE COCOA BEAN

    • HORSE CHESTNUT (seed shell)

    • HAWTHORNE FRUIT

    • GOAT WILLOW (catkin)

    • UNRIPE STRAWBERRY (fruit, stem)

    • UNRIPE RASPBERRY (fruit, stem)

    • COLA NUTS

    • PEANUT SKINS

    • GRAPE PIPS/SEEDS

    • RED WINE

    Commercial production of proanthocyanidins using grape seeds/pips is routinely practiced all over the world. It has been known since the 1960s that red wine is especially high in proanthocyanidins and several companies produce a red wine extract which takes advantage of this fact.

    Comparisons of grape pip/seed extract and pine bark extract with regard to their polyphenol content are shown in Table 2.

    PROPERTY GRAPE PIP/SEED EXTRACT PINE BARK EXTRACT
    % Polyphenols 92% 84%
    % Monomers (flavan-3-ol) 32% 38%
    % Oligomers (Proanthocyanidins) 68% 62%
    Oligomer/Monomer ratio 2.1 1.6
    Polyphenol/Monomer ratio 3.1 2.6
    Polyphenol/Oligomer ratio 1.5 1.6
    Table 2 — Comparison of Polyphenol Content of Grape Pip/Seed and Pine Bark Extracts
    Source: “Procyanidins de France” - brochure available from Crossover Marketing 203-481-8863

     

    4.0 BIOCHEMICAL PROPERTIES

    4.1 US Patent on Use of Proanthocyanidins

    In 1987, Jack Masquelier was granted US Patent No. 4,698,360 titled “Plant Extract with a Proanthocyanidins Content as Therapeutic Agent Having Radical Scavenging Effect and Use Thereof.” The abstract for this patent is given below:

    ABSTRACT

    “The invention provides a method for preventing and fighting the harmful biological effects of free radicals in the organism of warm blooded animals and more especially human beings, namely cerebral involution, hypoxia following atherosclerosis, cardiac or cerebral infarction, tumor promotion, inflammation, ischaemia, alterations of the synovial fluid, collagen degradation, among others. The method consists of administering ....... an amount, efficient against said effects, of a plant extract with a proanthocyanidins content which has a radical scavenger effect, the extract being in the form of a medicament and coming more especially from the bark of conifers.”

    Clearly, Masquelier is claiming a significant therapeutic effect for the proanthocyanidins by means of their potent free-radical scavenging ability. According to the abstract the proanthocyanidins can play a major role in the prevention and cure of a wide range of illnesses. The patent also specifies the dosages which need to be used in order to obtain the therapeutic effects claimed These are:

    • Orally – 1.5 to 3.0 mg daily per kilogram of body weight

    • Intravenously – 5 to 10 mg daily

    • Topically – application of 0.5% ointment one or more times daily

       

    In the following sections the research data which support Masquelier's claims will be reviewed.

    4.2 Bioavailability

    One of the key issues relating to the use of any nutritional supplement or medication is the ability of the substance to get into the body and be utilized at the cellular level. In order to demonstate the bioavailability of the oligomeric proanthocyanidins (PCOs), Masquelier and his colleagues used an isotopic labelling technique11. Grape vines were cultivated in an atmosphere containing 14CO2 for 40 days, during which time each carbon of the flavan molecule became labelled. After extraction and purification the product had an activity of 0.5 µCi per mg. When the PCOs were administered orally to a rat or mouse they became rapidly absorbed into the intestinal mucous membrane. The results shown in Figure 3 indicate that radioactivity in the blood was highest after 45 minutes with a half-life in the plasma of 5 hours. Passage into the bile occurs relatively early; within 11 hours almost 14% of the radioactivity was eliminated in this way.

    pycgraph1

    Figure 3 - Radioactivity in the blood of the mouse as a function of time after the administration of 14C labelled oligomeric proanthocyanidins

    Radioautographic techniques and measurement of the radioactivity in different organs were used to study the fixation and localization in tissues. The radioautographic cross-sections of the whole mouse showed the distribution of the radioactivity throughout the animal, with a preferential localization in tissues rich in glycosaminoglycans. Measurement of the radioactivity found in various organs is shown in Table 3 and confirms the results of the radioautographic measurements. Radioactivity observed in these experiments was associated with the PCOs (OPC) and not their degradation products since the fixation takes place in a matter of minutes well before any 14C appears in the exhaled breath.

    ORGAN RADIOACTIVITY COMPARED
    WITH TOTAL BLOOD
    Total Blood 1.00
    Muscle 1.09
    Heart Muscle 1.18
    Plasma 1.37
    Lungs 1.65
    Adrenal Glands 1.80
    Spleen 2.03
    Xyphoid Cartilage 2.77
    Skin 2.82
    Kidney, cortex 3.57
    Trachea 3.87
    Liver 5.40
    Duodenum 6.75
    Aorta 7.80
    Table 3 — Radioactivity of Various Organ Tissue Compared With That of the Total Blood

    The results of this study showed that the PCOs are rapidly absorbed into virtually all of the tissue of mammals (including the brain), and that there is a concentration in tissues high in glycosaminoglycans, namely connective tissues in the skin and organ systems, basement membranes of blood vessels, and cartilage.

    4.3 Oligomeric Proanthocyandins Effects on Collagen Fibers

    Collagen is the most abundant protein found in the human body. It is the key ingredient in the "glue" that holds us together and consists of helical structures of polypeptides connected together into long chains. Each collagen molecule actually consists of 3 chains, each of which is coiled in a left-handed helix. The three chains are twisted around one another, as the strands of a rope, to form a superhelix. It has been found that Vitamin C is needed in every step of the body processes by which collagen is made. The stability of collagen depends mainly upon the crosslinks which exist between the polypeptide chains.

    When collagen fibers are placed into hot water they undergo denaturation and contract rapidly. As the number of crosslinks increase, the contraction temperature increases. An important property of certain polyphenols is that they are able to attach onto collagen and create crosslinks. It is possible to measure the stabilizing effect of these polyphenols by observing the thermal contraction of the fibers onto which they become attached.

    In his laboratory, Jack Masquelier conducted a comparison study of the flavonoids with the proanthcyanidins (OPC)11. In the study, reconstituted beef tendon collagen fibers were incubated for 24 hours in an aquous solution of various test substances at a concentration of 1 mg/ml. Each fiber was 10 cm long and supported a weight of 5 grams. When plunged into water at 75°C the reference (untreated) fibers quickly shrank to 4 cm. Table 4 shows shows the contraction time of the various treated fibers, the calculated force of contraction, and the measured amount of the test substance that was actually attached to the collagen fibers.

    TEST SUBSTANCE CONTRACTION TIME (seconds) FORCE OF CONTRACTION 10-5W AMOUNT FIXED PER 100 mg OF COLLAGEN (mg)
    Reference Fibers 10 29.4 0
    Bioflavonoids 10 29.4 0
    Catechin 45 6.5 < 10
    Condensed Tannin 70 4.2 60
    Oligomers (PCOs)(OPC) 210 1.4 40
    Table 4 — Comparison of the effect on collagen fibers of the bioflavonoids with that of proanthocyanidins (OPC)

    The results show that the bioflavonoids have no effect as far as crosslinking and stabilizing collagen are concerned. Although catechin does indeed crosslink and stabilize collagen, the PCOs are over 4.5 times more effective than catechin. Furthermore, even though the collagen fixes 50% more of the condensed tannins than PCOs, the PCOs are three times as effective at stabilizing the collagen fibers. The conclusion is that the molecular configuration of the PCOs is optimal for the stabilization of collagen.

    4.4 Free Radical Trapping Effect

    The in vitro free-radical trapping effect of the OPC can be checked in several ways. The tetrazolium nitroblue (TNB) test12 is particularly effective at evaluating the effect of inhibition of superoxide radicals O2-. In this test oxygen radicals have the property of reducing TNB into formazan blue, the quantity of which can be colorimetrically determined at 560 nm. In the presence of antioxidants operating as O2- scavengers, reduction of the TNB is inhibited, which is demonstrated quantatively by a reduction of absorption at 560 nm. Table 5 shows the amount of inhibition obtained with a variety of substances.

    SUBSTANCE % INHIBITION
    Catechin-Catechin Dimer 78
    Epicatechin-Catechin Dimer 72
    Epicatechin-Epicatechin Dimer 63
    Malvoside 32
    Epicatechin 30
    Catechin 25
    Chlorogenic Acid 25
    Rutoside 24
    Cafeic Acid 20
    Ascorbic Acid 4
    Table 5 — Comparison of In Vitro Inhibition of Oxygen Radicals by OPCs With Various Other Substances

    The results show that the dimeric proanthocyandins are nearly 20 times more effective than vitamin C at trapping oxygen radicals, and are greater than two times more effective than the bioflavonoids and the monomers.

    Another similar study was reported by Masquelier11A, in which the NBT test was used to compare the ability of various substances to inhibit superoxide radicals, and the results are shown in Table 5A below. One sees that the the oligomeric proanthocyanidins are about 20 times more effective at trapping oxygen radicals than some of the commonly used bioflavonoids.

    NATURE OF THE SCAVENGER INCLUDED IN THE COMPARISON CONCENTRATION PRODUCING 50% INHIBITION (g/l)
    Procyanidolic oligomers (from grape seeds) 0.046
    Conventional citroflavonoids 0.900
    Hesperidine methyl chalcone 1.000
    Table 5A — Comparison of In Vitro Inhibition of Oxygen Radicals by Procyanidolic Oligomers with other flavonoids

    Another more recent and complete test compared the free-radical scavenger activity of procyanidolic oligomers and anthocyanosides with respect to superoxide anion and lipid peroxidation11B. In this study the NBT test was used for comparing superoxide activity. Lipid peroxididation induced by ascorbate and the Fe2+ - ADP complex was assessed in boiled rat liver microsomes. This system produces the hydroxyl radical OH-, which reacts with polyunsaturated fatty acids in microsomal membranes causing the uprooting of a H atom and the subsequent triggering of a cycle of fatty acid self-oxidation. The test is based upon the assay of malondialdehyde (MDA) released as a result of the degradation of lipoperoxides. The results of this study are summarized in Table 5B. This study shows the clear superiority of grape seed procyanidolic oligomers (OPC) as free-radical trappers.

    SUBSTANCE LIPID
    PEROXIDATION
    INHIBITION, mg/ml
    SUPEROXIDE
    INHIBITION IC50, mg/ml
    COMMENTS
    Vitis Vinifera L. (PCO) (grape seeds) 0.016 0.010 Grape Seed Extract
    Cupresses Sempervirens L. (PCO) 0.075 0.041 Extracted from berries
    Vitis Vinifera L. (AC) (juice) 0.090 0.039
    Vaccinium Myrtillus (AC) (bilberry) 0.095 0.041
    Ribes Nigrum (AC) 0.16 0.047 black currant extract
    Cyanidanol (reference monomer) 0.004/0.018* 0.051/0.019* *ref 14
    Ginkgo Biloba 0.25 ref 13
    BHA 0.084* 0.054* *ref 14
    Chlorpromazine 0.015* 0.031* *ref 14
    d-Alpha Tocopherol 0.034* *ref 14
    Table 5B — Comparison of Antioxidant Properties of Various Oligomeric Proanthocyanidins, Anthocyanidins, and Other Substances With Respect to the Inihibition of Superoxide Radicals and Lipid Peroxidation. IC50 Values are the Concentrations in mg/ml Needed to Inhibit 50% of the Free-Radical Reactions.
    Source: M.T. Meunier, E. Duroux, P. Bastide, Plantes medicinales et phytotherapie, 1989, Tome XXIII, n.4, p.267-274.
    Notes: PCO = oligomeric proanthocyanidins AC = anthocyanidins
    * references are from the source article

    Furthermore, using human umbilical cord and chicken embryo vascular tissue cultures the free-radical scavenging effect of pine bark extract was checked12A. Under certain conditions, these tissue cultures degenerate rapidly and in particular show destruction of the membrane phospholipids caused by oxygen radicals. When pine bark extract was added to the medium, the tissues cultures were maintained in a normal histologic condition.

    These results indicate that PCOs/OPC have very potent free-radical scavenging effects.

    4.5 In Vivo Tests of the Effect of Pine Bark Extract on Capillary Resistance

    Most of the studies described above were done in vitro or on animals. We will now present the results of a clinical study carried out with a total of 45 patients including 8 controls.13 The patients were suffering from skin diseases or phlebological illnesses (eczema, ulcerated varicose veins, etc.). Various bioflavonoids and pine bark extract were used to conduct this study. Capillary resistance was measured by means of a Parrot angiosterrometer which allows one to ascertain with precision the amount of suction which causes purpura (red spots from broken capillaries) to appear on the skin.

    In the first part of the study, patients were given a single 100 mg dose of pine bark extract and the capillary resistance was periodically measured over a 120 hour time inteval. The results are provided in Table 6.

    Hours immediately following administration (top) in relation to mean value of capillary resistance (bottom)

    Hours Immediately Following Administration
    0 1 3 6 10 24 48 72 96 120
    Mean Value of Capillary Resistance
    15 26 33 40 21 30 37 44 42 41
    Table 6 — Measurements of capillary resistance over a 120 hour time interval in 26 patients after the administration of a single dose of 100 mg pine bark extract

    It is observed that the mean capillary resistance increases rapidly peaking initially after 6 hours, then decreases and finally increases to its maximum value and remains at this high level. The term "diphasic" has been applied to this increasing, then decreasing, and finally increasing effect on the capillary resistance.

    The next part of the study looked at the effect on the capillary resistance of several other well-known bioflavonoids over a 120 hour period and compared the results with those obtained with pine bark extract. The results are displayed in Table 7.

    SUBSTANCE NUMBER OF PATIENTS NUMBER OF MONOPHASIC
    CURVES
    NUMBER OF DIPHASIC
    CURVES
    Pine Bark Extract 26 2 24
    Citroflavonoids 4 4 0
    Hesperidin 4 4 0
    Trihydroxyethylrutin 3 3 0
    Table 7 — Comparison of the Number of Diphasic and Curves for Various Bioflavonoids and Pine Bark Extract

    It is clear from the results shown in Table 7 that the traditional bioflavonoids do increase the capillary resistance for a short period of time, but none of those tested show the secondary long-term increase of pine bark OPC. Obviously, there is an effect from the pine bark OPC that is not inherent in the other traditional bioflavonoids.

    Table 8 shows the average percentage increase in capillary resistance over the first 72 hours after administration of the tested substance. This result indicates the almost threefold factor of effectiveness for pine bark OPC as compared to the other bioflavonoids.

    SUBSTANCE NUMBER OF PATIENTS AVERAGE INCREASE OF CAPILLARY RESISTANCE DURING 72 HOURS (% of starting value)
    Flavonoids 11 56
    Pine Bark OPC 26 140
    Placebo 8 3
    Table 8 — Mean Value of Increase of Capillary Resistance After 72 Hours for a Single Dose of the Test Substance Type

    Masquelier has concluded that the initial increase in capillary resistance shown with all of the bioflavonoids and oligomeric proanthocyanidins (OPC) is due to the effect that all of these substances have on inhibiting the enzyme Catecholamine O-Methyl Transferase (COMT) which is responsible for breaking down adrenaline in the body. The prolonged life of adrenaline caused by the flavonoids allows it to decrease capillary permeability (equivalent to increasing capillary resistance). The longer-term effect of increased capillary resistance shown only by OPC in the experiments comes about from the effect that the oligomeric proanthocyandins have upon Vitamin C. The PCOs/OPCs, which are powerful reducing agents, work with glutathione to reduce dehydroascorbic acid back to ascorbic acid within the tissues, which in turn is responsible for the increased capillary resistance by allowing the body to build or rebuild the collagen in the basement membranes of the capillaries.

    4.6 Effects of Oligomeric Proanthocyanidins on Histamine Formation

    During the initial stages of inflammation, damaged tissues release several chemical substances that activate the inflammation process. These include enzymes that breakdown or decarboxylate histidine into histamine which then increases the permeability of blood vessels. Middleton has reported that a number of the bioflavonoids inhibit histamine release thereby blocking the process of inflammation14. A study was conducted by Dr. David White at the University of Nottingham in England investigating the effect that pine bark OPC has on histidine decarboxylase14B.

    In the study, rat gastric mucosa were assayed in vitro for histidine decarboxylase (HDC) activity. HDC was measured by following the release of 14CO2 from 14C-histamine using the method of Beaven et. al.15. The results showed that HDC activity was inhibited in a dose dependent manner by OPC. An in vivo study was conducted by measururing HDC activity in the gastric mucosa of rats which had been given pine bark extract in their diet for 5 weeks at levels of 5 and 50 mg per kilogram of bodyweight. The HDC activity in animals treated at both high and low doses were reduced compared with controls, and, although this was not a very sensitive test, it confirms the in vitro results.

    4.7 Effect of OPCs and Catechins on Collagenases and Elastases

    Both in vivo and in vitro studies have provided evidence that the binding of oligomeric proanthocyanidins (OPC) to elastin affects its rate of degradation by elastases16. In these studies OPCs and (+) catechin bound to insoluble elastin markedly affected its rate of degradation by elastases. Insoluble elastin pretreated with PCO was resistant to the hydrolysis induced by both porcine pancreatic and human leukocyte elastases. (+) Catechin-insoluble elastin complexes were partially resistant to the degradation induced by human leukocyte elastase but were hydrolyzed at the same rate as untreated samples by a constant amount of pancreatic elastase.

    These studies emphasize the potential effect of these compounds in preventing degradation by elastases as occur in inflammatory processes.

    In another study17 treatment of radioactively labeled guinea-pig skin collagen or calf collagen with the bioflavonoid (+) - catechin makes the collagen resistant to the action of mammalian collagenase but not to the action of bacterial collagenase.....Since incubation of the mammalian enzyme with (+) - catechin does not inhibit its activity, it is postulated that (+) - catechin binds tightly to collagen and modifies its structure sufficiently to make it resistant to enzyme degradation.

    4.8 Effect of OPC on Blood Vessels

    Figure 4 summarizes the ways that OPC protect the blood vessels, especially the capillaries. Regulation of vessel resistance and permeability occur in three separate ways:

    pycfig4
    Figure 4 — Summary of How OPCs help protect the Blood Vessels

     

    • The OPC crosslink the collagen fibers in the vessel basement membranes which make them stronger and less permeable.

    • The OPC inhibit the production of histamine which prevents the histamine associated increase in permeability. In addition, OPC allow adrenalin to function for an extended time period by blocking the COMT enzyme, thereby allowing for increased vessel resistance.

    • By protecting and carrying vitamin C to the basement membranes, vitamin C is enabled to function more effectively in the production of the collagen needed to keep the vessels strong.

    Because much of the cholesterol produced in the body is broken down by Vitamin C, the protective effect that OPC have on Vitamin C indirectly helps the body to reduce high levels of cholesterol which may adversely affect the vessels by plague buildup on the walls.

    Some of the effects described above are properties of the common bioflavonoids, however, OPC have more potent as well as additional effects when compared to the common bioflavonoids. Based on the research, it can be expected that on an overall basis, OPC will be many times more effective at protecting the blood vessels than the common bioflavonoids.


    REFERENCES

    1. Walker, Morton, “Antioxidant Nutrients – Properties of the Most Powerful Antioxidant Nutrient Known to Man: Pycnogenol™.” The American Raum & Zeit, Volume 2, Number 3, 1991, 24–27.

    2. Walker, Morton, “Antioxidant Properties of Pycnogenol.” Townsend Letter for Doctors, August/September 1991, 616–19.

    3. Masquelier, J., Michaud, J., Laparra, J., Dumon, M.C., “Flavonoides et pycnogenols.” International Journal for Vitamin and Nutrition Research, 49, No3, 307–11, 1979.

    4. Masquelier, Jack, United States Patent Number 3,436,407, April 1969.

    5. Bate-Smith, E.C., and Swain, T., “Identification of Leuco-anthocyanidins as ‘Tannins’ in Food.” Chemistry and Industry, 1953, 377–78.

    6. Masquelier, Jack, “Pycnogenols: Recent Advances in the Therapeutical Activity of Procyanidins. Natural Products as Medicinal Agents.” Beal, J.L. and Reinhard, E., Eds., Supplement of Plant Medica, Journal of Medicinal Plant Research and Journal of Natural Products, LLoydia, July 1980, 243–55.

    7. Carper, Jean, The Food Pharmacy. Bantam Books, 1988, 84–90.

    8. Thompson, R.S., Haslam, J.E., and Tanner, R.J., Plant Proanthocyanidins. Part I. Introduction; the Isolation, Structure, and Distribution in Nature of Plant Procyanidins, J.C.S. Perkin I, 1972, 1387–90.

    9. Weinges, K. and Freudenberg, “Condensed Proanthocyanidins from Cranberries and Cola Nuts.” Chemical Communications, No. 11, 1965, 220–21.

    10. Weinges, K. et al., Procyanidine aus Fruchten, Zur Kenntnis der Proanthocyanidine, X, Liebigs Ann, Chem., Bd. 711, 1968, 193.

    11. Masquelier, Jack, “Pycnogenols: Recent Advances in the Therapeutical Activity of Procyanidins, Natural Products as Medicinal Agents,” Beal, J. L. and Reinhard, E., Eds., Supplement of Plant Medica, Journal of Medicinal Plant Research and Journal of Natural Products, LLoydia, July 1980, 243–55.

    11A. Masquelier, J, “Procyanidolic Oligomers (leucocyanidins).” Parfums, cosmetiques, aromes, n.95, octobre–novembre, 1990.

    11B. Meunier, M.T., Duroux, E. and Bastide, P., “Free-Radical Scavenger Activity of Procyanidolic Oligomers and Anthcyanosides with Respect to Superoxide Anion and Lipid Peroxidation.” Plantes medicinales et phytotherapie, Tome XXIII, No4, 1989, 267–74.

    12. Nishikimi, M., Rav, N.A., and Yagi, K., Biochem. Biophys. Res. Commun., 46, 1972, 849–54.

    12A. Masquelier, Jack, Plant Extract With a Proanthocyanidins Content as Therapeutic Agent Having Radical Scavenger Effect and Use Thereof, United States Patent Number 4,698,360, October 6, 1987.

    13. Masquelier, J., Pharmacodynamics: Human Pharmacology (Part IV A) No. 24.

    14. Middleton, Elliot Jr., The Flavonoids. TIPS, August 1984, 335–38.

    14B. David White, PhD, private communication, October 1990.

    15. Beaven, et. al., Anal. Biochem. 84, 638–41.

    16. Tixier, Godeau, Robert, and Hornbeck, “Evidence by in vivo and in vitro Studies that Binding of Pycnogenols to Elastin Affects its Rate of Degradation by Elastases.” Biochemical Pharmacology: Vol. 33, No. 24, 3933-39, 1984.

    17. Kuttan, R., Donnelly, P., and DoFerrante, N. “Collagen Treated with (+) - Catechin Becomes Resistant to the Action of Mammaliam Collagenase.” Experienta 37 (1981), Birkhauser Verlag, Basel (Schweiz).

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