Stem Cells and Naturopathy

Janis Bell, Ph.D., NMD (not to be quoted or distributed without written permission from drjanisbell@gmail.com) “Only one in every million cells in the human body—the stem cells—really matter. Everything else is just a product of these.” Dr. Stephen Emerson, Francis C. Wood Professor of Medicine, Abramson Cancer Center 1 Stem cells are everywhere in the news these days, promising ‘cures’ for everything from Parkinson’s to diabetes to heart disease. We heard these claims at the outset of genomics; and for those who remember the media hype of the past, there were similar promises from pharmaceutical companies when we started “The War on Cancer” and “The War on Heart Disease.” So we shake our heads and roll our eyes, wishing instead that we could get through to the mainstream media, government officials, and interested citizens on the necessity for a healthy diet, a healthy lifestyle, supplementation to counter our de-mineralized soils and toxic environment, positive emotions, and the power of body-mind-spirit practices. A truly holistic approach impacts all aspects of an individual’s well-being, regardless of where one chooses to first intervene. With the cost of removing and culturing stem cells, directing them to differentiate in vitro, and surgically implanting them in the body, the promise of stem cells may seem mere media hype, another high cost, high tech “silver bullet” keeping people from taking responsibility for their own health. Yet there is room for stem cells in naturopathy with our emphasis on non-invasive interventions. For recent advances have shown that the stem cells made every day in our body and released into circulation play a crucial role in the healing ability of the body. Indeed, there is increasing evidence that stem cells are the primary healing mechanism of the body. If you imagine being able to harness that ability, you will immediately understand that supporting the natural stem cell physiology of the body supports the natural healing process. We are just beginning to understand various aspects of this process. What are stem cells? A stem cell is an unspecialized cell that has the ability to continuously divide and differentiate into various kinds of cells. Stem cells can be thought of as “babies” who have no idea what they are going to be when they grow up. During embryonic development, various signaling molecules direct the cell to differentiate, narrowing its potential to become any kind of cell, until a particular ‘adult’ tissue type is formed. Once differentiated, cells divide a limited number of times and then die. Yet if before death, this tissue cell is damaged by toxins or oxidative activity, unless the cell self-destructs through apoptosis, it may make defective copies of itself, perpetuating damage to nuclear or mitochondrial DNA. In the mature organism, stem cells replace and replenish cells that are injured as well as those that have grown old and died. These cells respond to specific chemical signals and facilitate healing by differentiating into the specialized cells required for repair, provided they exist in sufficient numbers and receive the correct signals. When they do not, the end result is an inadequate healing response and the onset of disease, scarring, and permanent injury. There are many different kinds of stem cells. Those most controversial are embryonic

stem cells (ES). These are the cells from the inside of a blastocyst, a fertilized egg no more than 4-6 days old. At this stage, the embryo has not yet attached to the uterus and is a mere 0.1 millimeters across, smaller than the period at the end of this sentence. The cells are carefully removed with a pipette from the inner lining of the blastocyst and cultured in vitro on a bed of embryonic mouse fibroblasts known as feeder cells. These feeder cells provide a substrate for the ES cells to grow on while preventing their spontaneous differentiation.2 Embryonic stem cells also derive from germ cells taken from the gonadal ridge of a 5-9 week old fetus that has aborted spontaneously or purposefully. For political and ethical reasons, there has been less interest in pursuing research in these tissues in humans, but much has been accomplished with animal embryonic germ cells. When cultured on nondividing mouse feeder fibroblasts, these embryonic germ cells (EG) showed that they were capable of self-renewal and of differentiation into a wide variety of tissues. Unlike ES cells, they do not differentiate wildly, developing into teratomas, when injected into live organisms,.3 Until recently, scientists believed that embryonic stem cells were the only cells primitive enough to differentiate into any type of cell, a characteristic known as pluripotency. Consequently, the argument was put forth that the therapeutic potential of stem cell research depended upon the development of new embryonic cell lines. Imagined scenarios include the differentiation of cells in vitro through the identification of growth and differentiation signalers, the implantation of partially differentiated cells into humans as stem cell transplants, and – still in the realm of science fiction – the laboratory manufacture of human organs through precise control of growth and differentiation of cells. However, pluripotent stem cells have also been found in amniotic fluid and in umbilical cord blood. Fewer ethical concerns are attached to the use of these cells sources that do not require the destruction of life. Many people now pay to have their child’s cord blood frozen for later use, should the child need stem cells. Most of our patients have missed that chance. Embryonic and umbilical cord stem cells are being used therapeutically in many clinics and research centers. In some, fetal hematopoetic stem cells are injected intravenously into a patient or fetal neuronal stem cells are injected subcutaneously.4 Host rejection of foreign cells is a risk, although much less so than in organ transplants, despite DNA differences between donor and patient.5 I n others, a procedure called somatic cell nuclear transfer is used to make ES cells with an individual’s own DNA: the nucleus of a patient’s cell is injected into a denucleated donor egg which is allowed to mature to the blastocyst stage or later before implantation. With the donor’s own DNA, host versus graft disease (HVGD) is avoided, but the difficulty and expense of obtaining donor eggs limits the viability of this approach, especially when the prevailing ethics require that women undergoing surgery to donate eggs forego monetary compensation.6 Although some of these therapies are minimally invasive, none fit the naturopathic model of supporting the body’s ability to heal itself. Adult stem cells (ASC) are stem cells in any organism after birth, a misnomer sure to confuse the lay public’s association of “adult” with the maturity of chronological age. These cells are now known to exist in nearly every tissue of the body. Best known are those dividing most rapidly and therefore destroyed by chemotherapy. These include

stem cells at the bulge of hair follicles which replace hairs that are plucked out, yet which also leave their niche in large numbers to repair skin wounds.7 Others in the crypts of intestinal villi migrate towards the apices to continually replenish the short-lived cells responsible for absorbing nutrients; when the die, nauseau and malabsorption result. Bone marrow cells are released as hematopoietic stem cells which give rise to red and white blood cells as well as stoma cells which differentiate into cartilage and bone. When these cells are destroyed people develop anemia and low white blood counts. Less well known are the stem cells found in the brain which can differentiate into the three different types of brain cells: astrocytes, oligodendrocytes, and neurons; those found in the endothelium which can become blood vessel cells and cardiomyocytes; those in skeletal muscle which mediate muscle growth and repair from exercise and injury; and those in the liver, an organ frequently repairing itself. Just a few years ago, adult stem cells (ASC) were believed to be limited in their ability to differentiate. As a result, they were called multipotent, or unipotent, depending upon the number of different cell types that could be traced as their progeny, However, with advances in research techniques, particularly fluorescent labeling, researchers now have evidence that adult stem cells are pluripotent in the human body as well as in the bodies of numerous mammals. Moreover, in vitro studies have found ways to nudge ASC or their progenitor cells into a more primitive state which has increased their multipotency in the Petri dish. It has also led to a widely–held belief in the plasticity of ASC. When I went to school, textbooks on embryonic development stated that once a stem cell began to differential along a certain pathway, it had no choice but to continue along that pathway. Yet recent research has shown that these same cells, given the right conditions of signaling molecules and nutrients, can actually transdifferentiate. Neural stem cells in a Petri dish, for example, can produce insulin8 and mouse progenitor cells—the offspring of stem cells –were coaxed to revert to true stem cells.9 The first issue of Stem Cell Review in 2005 focused on the plasticity of adult stem cells, with most of the articles coming down in favor of ASC plasticity. Bone marrow stem cells seemed the most plastic of all, potentially becoming brain cells, skin cells, muscle cells, bone cells, glandular cells such as pancreas, adrenal, thyroid, thymus, and organ cells such as heart, liver, lung and digestive tract.10 Murine studies showed that ASC could become myocardial cells and endothelial cells after surgically-induced infarction.11 In testimony presented to the Maryland legislature in March 2005, Dr. David A Prentice wrote: “Bone marrow stem cells seem particularly ‘plastic,’ potentially with the ability to form all adult tissues.” He then went on to explain that cord blood cells and even stem cells from liposuctioned fat have shown the ability to transform into different types of tissues. In that same paper, Dr. Prentice summarized the therapeutic abilities of ASC implantation in a wide range of ailments -- 22 types of cancers, 3 neural-degenerative diseases and injuries, 1 ocular condition, 2 types of wound injuries, 12 auto-immune diseases, 1 cardiovascular condition, 1 type of immunodeficiency, 10 anemias and other blood conditions, and 4 metabolic disorders (including several that are hereditary genetic disorders.) In the last two years, the list of conditions successfully treated with ASC has grown exponentially.

Yet science proceeds slowly, especially when well-established beliefs are in question, and the plasticity of ASC defies the conventional dogma of developmental biology that development is in one direction and progressively restrictive. Studies need to be replicated; alternative explanations for data shown to be false. After the initial studies of ASC plasticity were published, critics alleged that the differentiated stem cells were not shown to function as normal cells of the new tissue, that the transplanted cell cultures were not pure, or that the cells had merely fused with tissue cells rather than truly differentiating into specific tissue types. But as Christopher Scott wrote in 2005 in response to the doubters: “The fact that hematopoeietic stem cells can help repair damaged organs is an important result and could lead to using stem cells as therapeutic agents.”12 Consequently, newer studies have controlled more rigorously for artifacts and purity and have made a point to demonstrate the functionality of these newly differentiated cells. Takashi Yazawa directed bone marrow stem cells from rats, mice and humans to become steroidogenic cells capable of producing testosterone (in mice and rats) and glucocorticoids (in humans).13 At the recent Wisconsin Stem Cell Symposium (April 18, 2007), Piero Anversa used multiple methods “including gene reporter assay, genetic tagging, cell genotyping, PCR-based detection of donor genes, and direct immunofluorescence with quantum dots … to document or disprove bone marrow cell transdifferentiation into functionally competent myocardium” and concluded “that locally delivered bone marrow cells generate de novo myocardium composed of integrated cardiomyocytes and coronary vessels. Importantly, this process occurs independently of cell fusion and ameliorates structurally and functionally the outcome of the post-infarcted heart.”14 There are so many studies at this date on ASC transdifferentiating into nearly every possible type of mammalian tissue that summarizing each would be impossible in a short review article. Interested readers can do a simple Medline search of ASC plasticity and the cell tissues of specific interest to each. Heart and neural tissue have been particularly promising avenues of inquiry with great therapeutic potential. It is of particular interest that ASC have shown to migrate to damaged retinal tissue and become new retinal cells, expressing retinal epithelium pigment – promising help for blindness arising from macular degeneration. One of the more interesting new developments in what has been called “postmodern biology” is the study of factors which account for uncertainty and “stochastic” behavior in the structure and function of cells. Neil Thiese at the Albert Einstein College of Medicine explained that “if the microenvironment around a cell (or if the cytoplasm around a nucleus) is altered, then the nature of the cell, namely its pattern of gene expression, is likely to change as well.”15 Isn’t this what naturopaths have been claiming for decades? Thiese hypothesized that the biology of uncertainty will complement the old biology as Quantum physics has complemented Newtonian physics whereby any attempt to observe or manipulate the cell will, by definition, alter it -- the Heisenberg uncertainty principle transferred to the behavior of genes and cells. Biological science is finally catching up to a truth that yogis and saints have articulated for millennia, and that modern energy healers and bodymind medicine have been promulgating: energy follows intention, and intention, whether originating in body, breath or mind, generates information molecules that change the

course of physical response and ideation. Supporting endogenous stem cell physiology In naturopathy, our goal is to support the self-healing mechanisms of the body, and the one thing that is becoming clear to everyone is that stem cells represents the principle way in which the body retains and repairs itself. So our purpose as practitioners supporting the healing power of the body is to optimize stem cell physiology in each individual. We can potentially intervene in the following three areas: 1. by increasing the number of circulating ASC 2. by creating a healthy environment for the survival of ASC 3. by supporting the migration of ASC towards those tissues in greatest need of repair Increasing the number of circulating ASC increases the probability that ASC will find all the target tissues that could benefit from repair and renewal. While most studies have increased ASC by implantation into the damaged organ, a few have looked at outcomes based upon increasing circulating ASC through intravenous or subcutaneous injection.16 ASC injected into circulation were found to become heart cells, vascular cells, and even brain neurons. A research team at the NIH led by Donald Orlic has published a number of papers on the role of adult circulating stem cells in the repair after heart attack.17 They found a link between mobilization of more stem cells from the marrow into the blood circulation, and increased speed of repair of the heart muscle after heart attack. Meanwhile, researchers in Maastricht have proposed that in the near future, stem cells may be used as predictive markers for the relative risk of atherosclerosis.18 The idea that therapeutic benefits for chronic degenerative disease would result from by increasing endogenous ASC was proposed by Jensen and Drapeau in 2002.19 Drapeau, a neuroscientist studying the properties of Aphanizomenon flos-aquae (AFA), a blue-green algae used as a superfood, wanted to determine what agents in AFA were responsible for reports of spontaneous healing that his company had been receiving from individuals ingesting this superfood. It was eventually discovered that AFA contains an l-selectin ligand that supports the release of stem cells (CD 34+) from the bone marrow. Preliminary studies and a triple blind randomized placebo-controlled study of 15 healthy volunteers between the ages of 20 and 65 were given 1 gram of an extract of AFA concentrate. At 60 minutes, CD34+ circulating stem cells increased by an average of 24 % (median 27%).20 Drapeau reasoned that, with circulating stem cells ranging between 1.5 and 5 cells per microliter, an increase of 30% amounted to a significant increase in the number of stem cells, on the order of 3 – 4 million stem cells. To put this in context, stem cell injections are on the order of about 2 million stem cells. Consequently, a sustained increase in numbers of circulating stem cells would presumably help many more people increase the healing potential of their bodies. Drapeau’s intuition turned out to have merit. In less than a year after launching the new AFA concentrate in the US supplement market as a product called StemEnhance™ (November 2005) testimonials started pouring in of people healing from a myriad of chronic conditions and distressing symptoms.21 A second way to support stem cell physiology is to create a healthy environment in the bloodstream to maximize the survival and potency of bone-marrow derived ASC. Johannes Waltenberger from the Academic Hospital in Maastricht explained that the functional contribution of circulating stem cells depends on a number of factors including the

ability to adhere to the endothelium, to migrate and proliferate, and to maintain their viability for the time needed. Pathological conditions that can impair these abilities include elevated lipids, elevated leukocytes, and diabetes, a condition that worsens the function of endothelial progenitor cells and inhibits the migration of the monocytes that contribute to vascular repair and collateral growth in cases of injury.22 Bickford et al. investigated natural compounds that affect ASC and showed that blueberry, green tea, catechin, carnosine, and vitamin D(3) were more effective than human granulocyte-macrophage colony-stimulating factor (hGM-CSF). 23 The synergistic combination of these compounds is being marketed through Life Extension. The prevalence of foods known to be high in anti-oxidants among this synergistic combination reminds us of the importance of adequate anti-oxidants to prevent free radical damage to the delicate lipid membranes of circulating ASC. Naturopaths have known that green foods, including the newer single cell algaes, have a beneficial effect on the blood and the health of body tissues.24 25 Chlorophyll alkalizes the blood by its high concentration of minerals, particularly magnesium. Chlorella and AFA have been studied for polysaccharides that chelate heavy metals. Metals such as mercury, lead, cadmium, aluminum, antimony and arsenic interfere with healthy metabolism by interfering with enzymes and competing with nutrient minerals. In addition, heavy metals create extensive free radical activity, adding to the toxic load that even the healthiest person must endure in our polluted world. Chlorella has been best studied for its ability to grab free mercury and remove it through the gut. AFA, although less studied, contains polysaccharides that were shown to absorb up to three times their weight in heavy metals.26 These oral superfoods work much more slowly than DMSA and DMPS because they do not mobilize metals from storage and therefore rarely show up as increased metal secretion in urine toxicologies. In my own practice, however, I have found consistent reduction of heavy metals by repeated hair mineral analysis-- without the risks of removing nutritional minerals and mobilizing heavy metals at a faster rate than an individual can dispose of them as occur in commonly used oral synthetic preparations. Inflammation has become an important topic of research in recent years due to the pivotal role it plays in numerous chronic conditions. In the field of stem cells, researchers have been focusing upon the role that inflammation may play in reducing the effectiveness of stem cell treatments.27 Chronic inflammation diverts stem cells from homing to the target tissue as they home to multiple inflammatory foci, Phycocyanin,28 the blue pigment in AFA, is a natural selective COX-2 inhibitor. AFA also contains carotenoids which have been shown in studies of Dunaliella and spirulina to be hepatoprotective.29 However, getting to the source of chronic inflammation, whether structural, infectious, or from toxicity, is always a valuable strategy and will lead to the most effective healing results. Food allergies and sensitivities are becoming increasingly recognized as an impediment to wellness. Food sensitivities originate in the gut, where the gut associated lymphoid tissue (GALT) is rich in white blood cells that mount an attack against the food molecules perceived as dangerous invaders. This attack causes localized inflammation that interferes with the absorption of nutrients, keeping the immune system in a constant state of alert, and diverting resources away from the more serious problem of rebuilding our target tissues. The most common food sensitivities and allergens (the difference being that sensitivities are not IgE mediated) are gluten, casein (bovine dairy), soy, beef, pork, and

peanuts. KD Fine at Enterolab has found in a six year study that 42% of the general US population has the gene for celiac sprue (HLA-DQ2 or DQ8). 30 A high percentage of these individuals have autoimmune disease rather than the gastro-intestinal symptoms traditionally associated with celiac disease, while a significant number have osteoporosis, headaches, allergies, autism spectrum disorders, and neuropathy. In addition, Fine has collected information on non-celiac gluten sensitivity relating to HLA-DQ1 and DQ3 (subtypes 7, 8, 9) which are even more prevalent in the US population leading to a whopping 86% of individuals with a genotype predisposed to react to gluten by creating antibodies. It is not easy to inspire patients to give up their favorite foods, and gluten, due to its mild opiate properties, is among the most addictive. Stool antibody testing and a simple DNA test from a cheek swap can make all the difference in convincing an individual that gluten-free is in his or her best interest for a healthy future. Lastly, researchers have identified a polysaccharide in AFA which is currently being studied for its ability to support the migration of stem cells into stressed tissues. While we await the publication of this research, there is much investigation of the mechanisms underlying how cells can move from one organ to another, engraft there, and take on the structure and function of their new home. One such mechanism involves stromal-derived factor-1 (SDF-1), a cytokine produced by cells of the target tissue (whether from injury or hypoxia) which is released into the circulation to attract cells with CXCR4-positive receptors.31 The process by which receptor cells home to the site of greatest concentration of a locally released peptide or information molecule is known as chemotaxis; its importance is discussed in lay terms in Candace Pert’s Molecules of Emotion.32 To the extent that more recently stressed tissues release more SDF-1 than chronically-stressed tissues, we may be close to understanding the mechanism through which self-healing of the body follows a course of reverse onset from most recent to oldest. The same polysaccharide fraction was also shown to strongly stimulate the activation of natural killer (NK) cells. NK cells play a very important role in the body by identifying aberrant or defective cells and eliminating them. NK cells are especially known for their ability to detect and destroy virally infected cells and cells undergoing uncontrolled cellular division. Pugh and Pasco found that AFA polysaccharide enhanced monocyte function by activating nuclear factor kappa B (NF-kappa B) and enhancing its DNA binding activity as well as increasing levels of two other cytokines.33 -34 The authors wrote that this polysaccharide is “between one hundred and one thousand times more active for in vitro monocyte activation than polysaccharide preparations that are currently used clinically for cancer immunotherapy.” The effect of AFA consumption on the ability of neutrophils to produce free radicals was also tested with the result that consumption of AFA actually slightly reduced the ability of neutrophils to produce free radicals. Thus, supplementing AFA can support whatever other efforts a practitioner may be taking to relieve the patient of acute and chronic infections. Stem cells, of course, also help to support a healthy immune system, since it is the hemapoietic stem cells which become the infection-fighting white blood cells. We know that the presence of infections in the body often impedes healing of other conditions because the body uses its energy to fight the infection. Steenblock reported the interesting case of a 83 year old man who recovered quickly from pneuomonia after a stem cell infusion but got no benefits in stroke recovery.35 Furthermore, the process of fighting infection gener-

ates a great deal of free radical activity, with the potential to damage stem cells coming to the rescue. In sum, a healthy environment for the survival and healing potential of ASC would include anti-oxidants, support for endogenous anti-inflammatory molecules, and addressing whatever toxins, infections, foods, and stressful emotions or behaviors are impeding the healing process. These are the basic principles underlying naturopathic intervention. But not everyone who complies manages to recuperate and rebuild. By combining these strategies with an increase in ASC, we have the potential to impact many more individuals. PEA (beta-phenylethylamine) - “the good-mood” molecule In this last section, I want to address a component of AFA which has neuromodulatory effects, since we all know how important a good state of mind is to recovery as well as the continued well-being of an individual. This compound, the mono-amine known as PEA has been concentrated in AFA extracts in amounts of 5 – 6.8 mg per capsule.36 PEA is the compound found in chocolate that is believed to produce its positive effect on mood, and our consequent desire for it whenever we have stressful thoughts. Chocolate has been found to be rich in antioxidants, relieving guilt from those who daily partake of its sensorial delights. Yet its PEA concentration is a mere 3 mg per kg, necessitating that one imbibe over 5 pounds of chocolate to get the same amount of PEA as one capsule of AFA concentrate.37 Moreover, the sugar in chocolate has deleterious effects on the immune system, the gut flora, and the nervous system, making AFA a preferable source for PEA. Studies have demonstrated the efficacy of PEA in depression and attention deficit disorders as well as in alcoholism and drug addiction.38 PEA is lipid soluble and readily crosses the blood-brain-barrier. Because it is found in low concentrations in mammalian brain and peripheral nervous tissues, it is known as a trace amine. Receptors specific to several trace amines have been recently identified.39-40 They are closely associated metabolically with the dopamine, noradrenaline and serotonin neurotransmitter systems in mammalian brain and have been shown to affect the release of acetylcholine.41 At pharmacological concentrations, trace amines have an “amphetamine-like” effect, while at lower concentrations, they possess postsynaptic modulatory effects that potentiate the activity of other neurotransmitters, particularly dopamine and serotonin.42 Consequently, individuals may experience increased energy, elevated mood, increased mental focus and alertness as well as a greater sense of calm, increased self-esteem, and improved sleep. PEA is produced in the body from the conversion of the essential amino acid phenylalanine. This conversion is enhanced by moderate exercise, explaining the euphoria often called “runner’s high.”43 Consequently, many individuals with mild depression get relief from physical exercise. But according to Sabelli, giving PEA to people with depression results in almost immediate improvement in 60% of cases.44 This pathway can also increase dopamine, for PEA is converted to tyrosine, which is then converted to dopamine. In those individuals with tendencies towards excessive excitatory neurotransmitters, the additional PEA can be balanced with support of serotonergic and GABAnergic pathways through targeted amino acid therapy and diet. Yet individuals with hyperexcitability, such as youngsters with ADD, seem to respond well to the addition of a naturally-occurring PEA in AFA. Recent studies show that PEA is a neuron-modulator rather than a stimulant.45

Although PEA isolates are considered safe, the naturally-occurring PEA in AFA and AFA concentrates is more in harmony with naturopathic principles both for the diversity of nutrients complexed with it and for the potential support repair of neural tissues that would optimally produce and respond to PEA more efficiently. With a growing number of animal studies reporting remarkable recovery of CNS and peripheral nervous system damage from stem cell therapies, we have nothing to lose and much to gain from exploring ways to support stem cell physiology in the widest population of patients. Clinical challenges Some patients present more challenges than others because of their sensitivities. I tried whole AFA (dried and liquid) in the past but could never tolerate the jumpy wired feeling that it created. As a result, I started cautiously with the new AFA extract and was pleased to find no adverse reaction, except for a few weeks of slightly loose stool as my gut flora adjusted.46 I have used the product with several hyper-sensitive individuals, starting them on less than ½ capsule a day and building up gradually. The partial contents of a capsule can be sprinkled on food. For those who cannot take capsules, mixing the contents of a capsule with organic virgin coconut oil and a small amount of organic raw honey provides a delicious nourishing treat. Allergic reactions are exceedingly rare. More often, sensitivities are the result of decompensation. As something in the body starts working again, everything begins to shift and the patient has symptoms of a healing crisis. When patients understand this, they are more willing to put up with the “funny feelings” as their body adjusts. In other cases, it may be beneficial to lower the dose in order to slow the process of detoxification. AFA is known to trigger detoxification. When this process proceeds too rapidly for the level of function of an individual’s organs of detoxification, discomfort ensues. Support bowel, kidney, liver, skin and lymph drainage until discomfort abates or detoxification is completed. Be particularly cautious in individuals with damaged or imbalanced detoxification pathways (CFS, FMS, hepatitis.) Ascertain that diet and supplements provide sufficient amino acids and nutritive minerals in an absorbable form. Urine and fecal testing for toxic metals, essential elements, and amino acids can help determine what is being excreted and what nutrients need to be supplemented to minimize discomfort and ensure efficacy of detoxification. Because an increase in stem cells lasts 4 – 6 hours, but peaks in one hour, those patients with challenging health conditions may benefit from taking repeated doses every 2-6 hours. In certain types of long-standing conditions, it may be advantageous to stress a tissue or organ to stimulate its endogenous production of the messengers that attract stem cells to repair a given tissue. Alternatively, specific RNA’s (Longevity Plus, Regeneresen) or glandulars may guide the focus of repair. While studies have shown that these RNA’s migrate to the body organs that are similar to themselves, we do not yet know how these molecules support repair and rebuilding. Mobilizing stem cells is a possible and likely mechanism. Similarly, in patients with high oxidative stress, antioxidants should be taken until measures (such as malondiaddehyde) are in a good range, and patients with clotting disorders and fibrin build-up should accompany stem cell therapy with fibrinolytic enzymes, such

as lumbrokinase or nattokinase, separate from stem cell enhancers, in order to clear narrow capillaries for optimal delivery to target tissues. In conclusion, integrating stem cell nutrition in a clinical practice will add to the success of protocols that support natural healing. For our well patients seeking health maintenance and healthy aging, supporting stem cell physiology brings a new dimension to antiaging by directly supporting the repair of the daily wear and tear on the body. The extent of this support coupled with the individuals intracellular and extracellular environment can do much to offset the anabolic deficit that normally increases with chronological age. For athletes, stem cell support can help them retain a competitive edge, allowing their bodies to rebuild more quickly and effectively after work-outs and competitions. For those with acute injuries, wounds, or recent surgeries, stem cell support can shorten recovery time and offer the possibility of a more complete recovery as studies of recovery from ischemic heart damage have shown. For patients with chronic illness who have reached a plateau in their recovery, stem cell support may be what they need to increase their healing power and move further along their healing path. Some individuals have reported taking high enough doses to provoke “spontaneous remission” of conditions that were previously scheduled for surgery! As naturopaths, we interpret these “remissions” as healings as expected responses of a self-healing organism rather than surprising “spontaneous” miracles. Many individuals experience a rapid increase in their sense of well-being, inspiring them to stick with all the other dietary and lifestyle changes that naturopaths recommend to the average American. Others need to be inspired to cultivate patience, since the natural healing of the body usually proceeds by targeting recent damage for first repair, much of which has not yet manifested as disease symptoms and is therefore not motivating the individual to seek treatment. In my experience over the course of a year, individuals are reporting increased energy, more stamina, fewer aches and pains, looking and feeling younger, feeling happier, sleeping better, faster recovery from exercise, brain working better, more focused, calmer, nicer skin, sharper vision, better hearing, able to reduce need for medications, recovery from long-standing health challenges, and not getting colds. We are (hopefully) used to similar reports in our clinical practice. Supporting stem cell physiology is another tool in our toolbox, one that promises to increase the potential for wellness among the growing numbers of Americans seeking guidance from alternative practitioners. Janis Bell NMD, Ph.D. is the founder of Holistic Health Network, a non profit corporation dedicated to the sharing of information about and resources for optimal health in body, mind and spirit. Holistic Health Network organizes community educational events and helps individuals in need obtain access to holistic treatment and products. She can be contacted at drjanisbell@gmail.com or 740-427-2650.

1 “Promise and Politics,” The Pennsylvania Gazette, Sept-Oct 2006, p. 51 2 Christopher T. Scott, Stem Cell Now, NY:Pi Press, 2006, 39-58. 3 Michael Bellomo, The Stem Cell Divide, NY:AMACOM, 2005, 48. 4 Institute of Cellular Medicine, Costa Rica and Mexico. 5 David Steenblock D.O. and Anthony Payne, Ph.D., Umbilical Cord Stem Cell Therapy, Laguna Beach: Basic Health Publications, 2006. 6 Hans Kugler’s International Academy of Anti-Aging Medicine,, http://www.antiagingforme.com 7 C Scott, Stem Cell Now, p. 87-8 8 Stuart Kim, et al., “Differentiation of insulin-producing cells from human neural progenitor cells,” Public Library of Science Medicine 2(4) (2005):e103. 9 Nicholas Forsyth, et al., “Telomerase and differentiation in multicellular organisms: turn it off, turn it on, and turn it off again.” Differentiation, 69 (2002):188-197. 10 DS Krause et al., “Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem Cell,” Cell 105, 369-377 (4 May 2001) 11 Jackson, K.A., Majka, S.M., Wang, H., Pocius, J., Hartley, C.J., Majesky, M.W., Entman, M.L., Michael, L.H., Hirschi, K.K., and Goodell, M.A. (2001). Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J. Clin. Invest. 107, 1–8; Kocher, A.A., Schuster, M.D., Szabolcs, M.J., Takuma, S., Burkhoff, D., Wang, J., Homma, S., Edwards, N.M., and Itescu, S. (2001). Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat. Med. 7, 430–436; Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S.M., Li, B., Pickel, J., McKay, R., Nadal-Ginard, B., Bodine, D.M., Leri, A., and Anversa, P. (2001). Bone marrow cells regenerate infarcted myocardium. Nature. 410, 701–705. 12 C Scott, Stem Cell Now, 93. 13 T Yasawa et al, “Differentiation of Adult Stem Cells Derived from Bone Marrow Stroma into Leydig or Adrenocortical Cells” Endocrinology Sep 2006; 147: 4104 - 4111. 14 On line abstract at http://www.zoolgi.com/conferences/wisconsin-stem-cell-symposium-april-18-2007-a-3837.html 15 Implications of 'postmodern biology' for pathology: the Cell Doctrine, Laboratory Investigation (2006) 86, 335–344. doi:10.1038/labinvest.3700401; published online 13 February 2006. 16 Steenblock and Payne, Umbilical Cord Stem Cell Therapy, p. 18, used all 3 approaches in successful treatment of MS. Cerebral palsy, ALS, stroke, and traumatic brain injury. 1717 See www.stemcells.nih.gov and Hematopoietic Stem Cells V, vol 1044, 2005, ed. Lothar Kanz et al., June 2005. 18 See the news release in Stem Cell Research News, Oct 2005 at http://www.medicalnewstoday.com/medicalnews.php?newsid=31430 19 G. Jensen, C. Drapeau, The use of in situ bone marrow stem cells for the treatment of various degenerative diseases, Medical Hypotheses 59(4):422-28. 20 Study results available online at http://www.learnmore.stemtechbiz.com under “learn more.” 21 Independent testimonials have been collected through Health News (downloadmyebook.com) and on several websites. Stem Tech Health, Inc. does not endorse any testimonials that imply that a food supplement can cure, treat, prevent, or mitigate disease in compliance with FDA regulations. 22 See the news release in Stem Cell Research News, Oct 2005 at http://www.medicalnewstoday.com/medicalnews.php?newsid=31430 23 Nutraceuticals synergistically promote proliferation of human stem cells, Stem Cells Dev 2006 15 (1):1118-23. 24 RA Kay, Microalgae as food and supplement, Crit Rev Food Sci Nutr, 1991;30(6):555-73. 25S. Singh and BN Kate, Bioactive compounds from cyanobacteria and microalgae: an overview, Crit Rev Biotechnol, 2005 Jul-Sep;25(3):73-95. 26 C.Drapeau, Primorial Food, Aphanizomenon flos-aquae, a Wild Blue Green Algae with Unique Health Properties, 2003. 27 F. Mourkioti N. Rosenthal, “IGF-1, inflammation and stem cells: interactions during muscle regeneration,” Trends in Immunology 26(10): 535-542, October 2005.

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43 A. Szabo, E. Billett, J. Turner, Phenylethylamine, a possible link to the antidepressant effects of exercise?” Br J Sports Med. 2001
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44 http://www.webmd.com/content/article/34/1728_90004.htm 45 N Berretta et al,, Trace amines reduce GABA(B) receptor-mediated presynaptic inhibition at GABAergic synapses of the rat substantia nigra pars compacta, Brain Res. 2005 Nov 16;1062(1-2):175-8. Epub 2005 Nov 2 46 Several species of fecal bacteria, including bacteriodetes, have been found to express beta-phenylethylamine indicating that ingestion of this cyanobacter may have a beneficial impact on gut bacteria.