Clinical Research

  

Effectiveness of EZPAK Nutraceuticals in raising serum vitamin, mineral and amino acid levels in patients 26 to 75 years of age.

S. Osguthorpe, N.D.

Introduction

Abundant scientific and clinical literature indicates that dietary supplements can play an important role in promoting health and reducing disease. The general public has embraced dietary supplements as an integral part of their daily health program. National surveys report that approximately one-half of adult Americans use supplements on a daily basis1. Supplement usage increases with age, income, and education and is more common among women than men. Supplements are also widely consumed by healthcare professionals. Female physicians use supplements at rates equal to those of females in the general population. The Council for Responsible Nutrition reports that 44% of cardiologists, 38% of nurses, 60% of dieticians, and 47% of pharmacy students routinely take supplements2. Multivitamin/mineral supplements are the most widely used. One survey conducted by the National Nutritional Foods Association reported that the overwhelming majority of respondents expect to receive information about supplement use from their pharmacists (84%) and physicians (80%). Healthcare providers should be informed about what supplements their patients are taking so as to prevent drug-nutrient interactions and potential toxic levels of some nutrients, and ensure proper balanced nutritional intake.

Nutritional inadequacies are unfortunately a common occurrence in the U.S. and other industrialized nations because of diets low in fruits and vegetables and high in energy-dense, processed foods3. In addition to encouraging healthier food choices, supplementation is recommended when an individual’s dietary nutrient intake is inadequate or unbalanced. Levels of nutrient intake at or slightly above the official Recommended Dietary Allowances (RDA) may be adequate to help individuals achieve a more complete and balanced intake of vitamins, minerals and trace elements4. However, higher doses in excess of the RDAs may be needed to meet individual requirements that vary with age, level of physical activity, stress, genetic factors, medication usage, toxic burdens, or disease5. While RDA levels of intake may prevent overt nutrient deficiencies, chronic nutrient insufficiencies may result in altered metabolic activities that lead to physiologic dysfunction associated with many common health problems encountered today6. Ensuring increased amounts of vitamins and minerals may assist more optimal functioning of interrelated enzyme systems, cellular energy metabolism, hormonal regulation, and detoxification pathways that are critical to maintaining health7.

Ingredient Profile

The amounts as well as the forms of each nutrient in EZPAK have been selected to help ensure a high degree of nutrient bioavailability, tolerance, and safety with daily, long-term use. A broad spectrum of essential vitamins, minerals, and trace elements is included to take best advantage of the combined synergies and related metabolic functions of these nutrients. Herbal ingredients are not included, thus making this foundation product suitable for most patients without concern over taking inappropriate ingredients. Unlike common, over-the-counter multivitamins8 9 10, the higher potency amounts of ingredients in EZPAK offer greater nutritional benefits. Some of the distinguishing characteristics of EZPAK include:

Vitamin A/Carotenoids: Fat-soluble vitamin & antioxidant - Essential for skin, hair, nails and eyesight; helps cells reproduce normally; required for normal reproductive function. Both preformed vitamin A and its carotene precursor are included to help ensure more complete vitamin A nutrition. Diabetics and those with hypothyroidism11 often have insufficient conversion of beta-carotene to vitamin A, and providing beta-carotene alone may not be sufficient to support immune cell activation. The natural, unsaturated cis form of vitamin A (retinol) from fish liver oil is used instead of the synthetic12 trans form supplied by vitamin A palmitate. This avoids potential difficulties in absorbing the synthetic form as occurs in individuals with compromised intestinal function. Mixed, natural-source carotenes are used instead of synthetic beta-carotene for more complete antioxidant action.

Vitamin C/Bioflavonoids: Water-soluble vitamin & antioxidant13 - Causes cells to bind; helps to firm skin, tissue and blood vessels; protects LDL cholesterol from oxidative action; reduces stiffness in arteries and inhibits the clumping of platelets. A buffered, mineral-bound form of vitamin C is utilized to avoid the normal acidity of ascorbic acid to which some individuals may be sensitive. A concentrated source of citrus bioflavonoids complements vitamin C activity.

Vitamin E Complex: Fat-soluble vitamin & antioxidant - Protects cell membranes and other fat soluble tissues14; helps the body process glucose; prevents lipid peroxidation. 100% natural vitamin-E complex, including all naturally occurring tocopherol isomers (d-alpha, d-beta, d-gamma, and d-delta) is used for synergistic benefit and balanced actions.

Vitamin D: Fat-soluble vitamin - Maintains calcium in the blood by absorbing calcium from food and urine, allowing the body not to compromise the calcium in the bone15; plays a role in immunity and blood cell formation. Natural source vitamin D3 is included at 100% of the recommended daily intake (400 I.U.).

Vitamin B Complex: All B-complex vitamins are included for synergism and balance. Significant amounts of folic acid in its active forms folinic acid and (5-methyltetrahydrofolate), vitamin B6, and vitamin B12 in its active forms (methylcobalamin and S-adenosylcobalamin) are included to assist proper methylation and reduce the risk of toxic build-up of homocysteine16

Thiamine - Water-soluble vitamin (B1) - Aids in the processing of carbohydrates, fats, and protein; needed to form ATP--the fuel the body runs on; helps proper functioning of nerve cells17.

Riboflavin - Water-soluble vitamin (B2) - Needed to process amino acids and fats; helps to convert carbohydrates to energy or ATP; acts as an antioxidant18

Niacinamide - Water-soluble vitamin (B3) - Activates enzymes19 involved in food breakdown; aids in the process of releasing energy from carbohydrates. 

Vitamin B-6 - Water-soluble vitamin (pyridoxine) - Processes amino acids; an essential nutrient in the regulation of mental processes and mood20; aids in protein metabolism/absorption; red blood cell and nerve function. 

Folate - Water-soluble vitamin - Necessary for manufacturing DNA and RNA21, and for making red blood cells; keeps homocysteine levels in the blood from rising, thereby lowering heart disease risk; may help lower risk of certain cancers. 

Vitamin B-12 - Water-soluble vitamin (cobalamin) - nucleic acids - needed for normal nerve cell activity22, DNA replication, and the production of red blood cells; aids in lowering homocysteine levels. 

Pantothenic Acid - Water-soluble vitamin (B5) - Involved in the Krebs cycle of energy production, needed to make the neurotransmitter, acetylcholine23 (the memory maker). 

Biotin - Water-soluble vitamin (B complex) - Acts as a coenzyme in the metabolism24 of protein, carbohydrates, and fatty acids25.

Mineral/Trace Elements: Fully reacted mineral and trace elements, which are noted for their high bioavailability and tolerance, are used for zinc, magnesium, manganese, copper, and several other minerals. Organically bound forms of chromium and vanadium are included for high physiologic activity of these trace elements. Iron is not included since most adults (men and post-menopausal women) do not require supplemental amounts of this mineral which may be a potentially harmful pro-oxidant. 

Calcium - Mineral - The most abundant mineral in the body; is needed to form strong bones and teeth; required for proper nerve function and muscle contraction; essential for blood clotting26

Iodine - Mineral - Needed to make the thyroid hormones27, which maintain normal metabolism in all cells of the body.

Magnesium - Mineral - Needed for tendon, muscle, and bone structure; helps lower blood pressure; activates the B vitamins; helps form ATP28

Zinc - Mineral - Is a component of more than 300 enzymes involved in wound repair; boosts immunity; battles free radicals; helps cells reproduce; aids in the preservation of vision29

Selenium - Mineral - Activates an antioxidant enzyme glutathione peroxidase, which helps protect the body from cancer; essential for healthy immune functioning by stimulating white blood cells30; assists vitamin E in preventing breakdown of fats. 

Manganese - Mineral - Needed for healthy skin, tendon, cartilage, and bone formation; necessary for glucose tolerance; helps activate superoxide dismutase (SOD)31.

Chromium - Mineral - Helps the body maintain normal blood sugar levels32; increases HDL (good) cholesterol and lowers total cholesterol levels; has a potential role in positively altering body composition33.

Molybdenum - Mineral - Essential in the metabolism of iron34.

Potassium - Mineral - Regulates water balance35, levels of acidity, and blood pressure; aids in nerve transmission and metabolism.

Inositol - Mineral - Required for proper formation of cell membranes36. It aids in nerve transmission37 and helps transport fats within the body. The complementary and documented roles in neuronutrition are supported by other key neuronutrients in the EZPAK vitamin/mineral formula. Used daily, this combined spectrum of nutrients may improve absentmindness and other mild memory problems associated with aging.

Numerous age-related changes take place in neuronal and behavioral function, even in the absence of neurodegenerative disease38. These include impairment of brain microcirculation, alterations in neurotransmitter synthesis and function, imbalance in hormonal function in response to chronic stress, and free radical-induced damage to nerve cell membranes and metabolic activities. As a result, most individuals over the age of 40 experience some decline in memory retention, concentration, and acuity. This is technically referred to as Age-Related Cognitive Decline (ARCD)39 or Age-Associated Memory Impairment (AAMI)40.

Recent research strongly suggests that numerous dietary components can impede and, in some cases, reverse the course of deleterious neuronal aging. Normal age-related decline in cognitive function is characterized by decreased concentrations of multiple chemical transmitters. Thus, excessive activation of just one or a few pathways may result in an undesirable imbalance in nerve cell communication and brain function. Because optimal brain function is dependent upon the multiple neurotransmitter networking profile, the following nutrients in EZPAK have been selected to help the body produce and maintain a proper balance of the different neurotransmitter pathways to support healthy mental capacity.

Acetyl-L-Carnitine41: Acetylcholine is a principal neurotransmitter involved in memory and learning. Cholinergic function declines with aging and may be due to loss of nerve cells in learning and memory areas, a decline in neurotransmitter output, or a combination of both. Aging is also associated with a decline in the production of nerve growth factor (NGF) and the number of NGF receptors. Acetyl-L-carnitine, the acetylated ester of the amino acid L-carnitine, has been demonstrated to increase the synthesis and release of acetylcholine, retard and partially reverse the loss of neurons from the hippocampus and prefrontal cortex, and partially reverse the negative changes in NGF metabolism. Acetyl-L-carnitine also increases cerebral blood flow in patients with cerebrovascular disease. The L-carnitine moiety is essential for the transport of long-chain fatty acids into nerve cell mitochondria where they serve as a primary fuel for cellular energy production. It also helps maintain the bound-to-free coenzyme A (CoA) ratio and removes toxic concentrations of acetyl-CoA within the mitochondria, thereby helping to ensure that energy production can continue. Due to its central role in energy metabolism, L-carnitine is especially needed to support tissues such as brain, which have a high-energy requirement.

L-Glutamine42: A conditionally essential amino acid, L-glutamine serves as a major precursor molecule to the synthesis of two important neurotransmitters: the excitatory L-glutamic acid and the inhibitory gamma-aminobutyric acid (GABA). Glutamate also plays an important role in secondary metabolic functions in the neocortex where it assists detoxification of ammonia and serves as a building block of proteins.

L-Pyroglutamic acid43: L-Pyroglutamic acid, a natural glutamate metabolite, increases acetylcholine release, cerebral blood flow, and brain metabolism. It stimulates cholinergic nerve cell metabolism by increasing the uptake and utilization of glucose while at the same time decreasing brain lactate dehydrogenase activity, thus enhancing anaerobic glycolytic activity. Blocking of glutamate receptors by L-pyroglutamic acid stimulates acetylcholine release in cortical cells. This causes GABA levels to rise, followed by cortical acetylcholine release.

L-Tyrosine44: This non-essential amino acid is used by the brain to make catecholamine neurotransmitters including dopamine, norepinephrine, epinephrine, and L-DOPA. Norepinephrine has a general energizing effect while elevating mood, countering stress, and contributing to short-term memory and concentration. Dopamine also helps elevate mood and is the principal neurotransmitter involved in central nervous system control of muscle movement. Tyrosine has been reported to improve mental function that may be impaired by stress, sleep deprivation, and depression.

Dimethylaminoethanol (DMAE)45: Dimethylaminoethanol is a naturally occurring compound produced in small amounts in the brain. Studies show that exogenous DMAE results in increased levels of choline in the blood and brain. However, unlike choline itself, DMAE crosses the blood-brain barrier more effectively, enabling it to reach the brain and increase choline levels more efficiently. The increased availability of choline in the brain is believed to speed the production of acetylcholine, a crucial neurotransmitter involved in memory, learning, recall and thought processes.

Ashwagandha (Withania somnifera)46: This Ayurvedic herb exerts an anti-stress neuroprotective effect. This may be due to its antioxidant action and the ability to decrease stress-induced cortisol release. Cortisol interferes with the brain’s supply of glucose and neurotransmitter function, and causes excessive influx of calcium that, over time, produces increased free radical formation leading to nerve cell damage and death. Ashwagandha extract also increases cortical cholinergic activity thus contributing to an enhancement of memory and cognition.

Blueberry (Vaccinium corymbosum) Extract47: Polyphenolics, such as found in blueberries, exert potent antioxidant protection against oxidative stress in the central nervous system. Neurons become increasingly susceptible to oxidant damage with age, which may contribute, at least in part, to neurodegenerative changes. Considerable evidence exists showing antioxidants neutralize free radicals and the consequent oxidative damage they generate may produce a slowing down or even a reversal of age-related declines in neuronal signaling and cognitive performance. Polyphenolics found in blueberry extract are among the most effective agents that neutralize free radical activity. Rats fed blueberry extract show significant reversals in neuronal signal transduction, cognitive, and motor deficits.

Ginkgo Biloba48: Numerous studies support the effectiveness of Ginkgo biloba extract for improvement of cognitive function and memory. Two groups of compounds, ginkgo flavone glycosides and terpene lactones, are considered to be the primary active constituents. These are responsible for enhancing cerebral microcirculation through a relaxing effect on vascular walls and an anti-platelet aggregation activity. This produces an increased delivery of oxygen to nerve cells that facilitates glucose utilization and enhancement of memory and cognitive functions. Besides improving circulation, the glycoside and lactone constituents prevent oxidative damage to nerve cell membranes, mitochondria, and biochemical processes by suppressing the production of active nitrogen and oxygen reactive species and thereby producing an anti-inflammatory effect. Ginkgo is reported to enhance cholinergic activity by inhibiting age-related loss of acetylcholine receptors and stimulating choline uptake in hippocampal neurons.

Eleuthero (Eleutherococcus senticosus)49: Like ashwagandha, Eleuthero is reported to protect the brain by helping to reduce stress-induced release of cortisol. This occurs, at least in part, through an inhibition of enzymes that limit the binding of stress hormones to their receptors.

Vinpocetine50: Vinpocetine, derived from vincamine, a compound found in the leaves of the periwinkle plant, has been widely used in Europe for many years to aid memory and support healthy brain function. It has been shown in numerous studies to exert its benefit on the brain through several mechanisms of action. Cerebral blood flow is increased through cyclic GMP-induced myorelaxation producing regional vasodilation, normalization of erythrocyte flexibility, and inhibition of platelet aggregation. Oxygen uptake by nerve cells is increased, thereby reducing damage caused by hypoxic conditions. Mitochondrial respiratory rate is increased in mitochondrial suspensions. This may act to increase glucose utilization and the rate of ATP production thus enhancing overall brain energy levels. Vinpocetine also acts as an antioxidant, preventing the formation of reactive oxygen free radicals and lipid peroxidation in synaptosomal preparations.

GlyceroPhosphoCholine (GPC)51: GPC has been extensively researched for its brain benefits. Supplementation with GPC has been shown in numerous clinical studies to significantly benefit attention, mental focus, recall and other higher mental functions in young, middle aged and elderly subjects. In addition to being a normal metabolic precursor of acetylcholine, GPC also acts as a precursor to phosphatidylcholine, the most common phospholipids in nerve cell membranes. Therefore, GPC’s vital role to both the individual nerve cell and their electrical integration via acetylcholine production may account for its impressive spectrum of clinical benefits.

Phosphatidylserine52: Phosphatidylserine exerts a restorative effect on memory via several different, but complementary actions. It corrects age-related cholinergic deficiency by increasing the availability of choline for acetylcholine synthesis and correcting the decline in cholinergic receptors. It helps maintain nerve cell membrane fluidity thus allowing for efficient transport of compounds, including glucose and other needed nutrients, both within and across the membrane in various brain regions. And, it helps balance the neuroendocrine response to stress characterized by the excessive release of ACTH, cortisol, and adrenaline.

Study Design

This study of EZPAK Nutraceuticals was designed as a random selection of 250 patients from a pool of 1400 (200 given EZPAK and 50 control). The patients had a medical history taken and a physical examination preformed that included serum levels to serve as a base line. Following the data pooling an additional statistician evaluated and correlated the results. The construction of the study was to measure the capability of EZPAK Nutraceuticals to increase the serum levels in the study group at the end of three months.

This study consisted of an initial serum draw and subsequent draws at 1 month, 2 months and 3 months. Vitamins tested included A, E, B1, B2, B6, B12, C, D. Minerals were Calcium and Iron. IGF1 and FT3 were included to assess any increase in growth hormone and thyroid function.

Method of Study 

In the first phase, each of the patients was randomly assigned to the study after appropriate approval was granted. A complete medical and surgical history was obtained at the time of the study and all of the necessary supporting laboratory data was obtained to assess the current serum levels. 

Analysis of Data

The patient population ranged in age from 26 to 75 with a mean age of 49.7years. The average of the females was 48.8 years while the males were 51.2 years. There were 117 females in the study as compared to 132 males. 

Results

The patients taking EZPAK experienced an overall serum increase of 31.3% at three months. This increase was consistent over the range of testing. The control group had a decrease of 16% in Vitamin D and 2% in calcium. The decrease probably was seasonal variance of the sun53.

A: 36% Test Methodology; High Performance Liquid Chromatography (HPLC)

E: 27%  Test Methodology; High Performance Liquid Chromatography (HPLC)

B1: 42% Test Methodology; High Performance Liquid Chromatography (HPLC)

B2: 42% Test Methodology; High Performance Liquid Chromatography (HPLC)

B6: 59% Test Methodology; Liquid Chromatography Tandem Mass Spectrometry

B12: 35% Test Methodology; Immunoassay

C: 28% Test Methodology; Capillary Electrophoresis

D: 30% Test Methodology; Chromatography

Calcium: 9% Test Methodology; Arsenazo III

Iron: 27% Test Methodology; Ferozene

IGF-1: 29% Test Methodology; Immunoassay

FT-3: 11% Test Methodology; Chemilumine

Because the majority of the effects of low vitamin, mineral and amino acid deficiency can be prevented or reversed by nutraceutical replacement, the clinician must be able to identify those patients who are most at risk and recognize the subtle clinical signs and symptoms of the deficience. It is important to consider that there may be a wide variation in the clinical presentation. Laboratory assessment is the optimal approach to confirm the diagnosis. 

This study has demonstrated the effectiveness of EZPAK Nutraceuticals in treating patients with low serum levels of vitamin, mineral and/or amino acids.   

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1Dickinson A, Boyon N, Shao A. Physicians and nurses use and recommend dietary supplements: report of a survey. Nutrition Journal 2009, 8:29doi:10.1186/1475-2891-8-29.


2Frank E, Bendich A, Denniston M. Use of vitamin-mineral supplements by female physicians in the United States. Am J Clin Nutr 2000;72:969-975.


3American Journal of Clinical Nutrition, Vol. 88, No. 2, 578S-581S, August 2008


4§ 101.54 Nutrient content claims for “good source,” “high,” “more,” and “high potency.”


5Dietary Reference Intakes (DRIs): Recommended Intakes for Individuals, Food and Nutrition Board, Institute of Medicine, National Academies, 2009


6Vitamin D2 treatment for vitamin D deficiency and insufficiency for up to 6 years.

Pietras SM, Obayan BK, Cai MH, Holick MF. PMID: 19858440 


7U.S. Department of Agriculture, Agricultural Research Service. USDA Nutrient Database for Standard Reference, Release 22, 2009.


8Kiely M, Flynn A, Harrington KE, et al. (October 2001). "The efficacy and safety of nutritional supplement use in a representative sample of adults in the North/South Ireland Food Consumption Survey". Public Health Nutr 4 (5A): 1089–97.


9National Institutes of Health State-of-the-Science Panel. National Institutes of Health State-of-the-Science Conference Statement: multivitamin/mineral supplements and chronic disease prevention. Am J Clin Nutr 2007;85:257S-64S


10Hoffer A, Walker M (2000). Smart nutrients. Avery. ISBN 0895295628.


11Fatourechi V. Subclinical hypothyroidism: an update for primary care physicians. Mayo Clin Proc. 2009;84(1):65-71.


12Chopra RK, Bhagavan HN. Relative bioavailabilities of natural and synthetic vitamin A formulations containing mixed tocopherols in human subjects. Int J Vitam Nutr Res. 1999 Mar;69(2):92-5.


13Krukoski DW, Comar SR, Claro LM, Leonart MS, do Nascimento AJ. Effect of vitamin C, deferoxamine, quercetin and rutin against tert-butyl hydroperoxide oxidative damage in human erythrocytes. Hematology. 2009 Jun;14(3):168-72.


14Ohta Y, Imai Y, Kaida S, Kamiya Y, Kawanishi M, Hirata I. Vitamin E protects against stress-induced gastric mucosal lesions in rats more effectively than vitamin C Biofactors. 2010 Jan 20.


15Hewison M, Adams JS. Vitamin D insufficiency and skeletal development. J Bone Miner Res. 2010 Jan 15;25(1):11-13


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