of the American Naturopathic
By: Charles E. Curtis
Happy Holidays to one and all. In spite of 9 1 1 ANMA had a wonderful convention, with a good response from the medical community nationwide. In these trying times we have a lot to be thankful for. The naturopathic community, as well as other natural health care professions nationally, have been very good to ANMA. In the coming year, we’ll have our usual work laid out for us. For the time being, we should all give thanks for the many fine opportunities that have come our way. ANMA wishes you and yours a happy and prosperous New Year.
Natural B Vitamins Are Better
By: Robert J Thiel, Ph.D., Naturopath
Portions of this article were previously published as Thiel R. Natural vitamins may be superior to synthetic ones. Med Hyp, 2000;55(6):461-469 Harcourt Publishers and Thiel, Robert J. Combining Old and New: Naturopathy for the 21st Century. Whitman Books, 2000.The book is available from www.healthresearch.com or www.amazon.com
At our office, we sometimes recommend products which contain various B vitamins. Some of our clients have indicated that the synthetic B vitamins that they take are at least as good because they normally contain higher amounts of the individual vitamins than the food formulas we normally recommend. Is this true? Are humans better off eating higher amounts of un-natural synthetics or smaller amounts of food complex B vitamins?
United States Pharmacopoeia (USP) synthetic vitamin B isolates are not food, even though they are often called "natural" and are sometimes added to foods—they are synthesized, standardized chemical isolates . In nature vitamins are never isolated: they are always present in the form of food vitamin-complexes [2-4]. This paper will discuss some of the physiochemical differences between individual natural B vitamins and synthetic ones, as well as cite clinical research which suggest that vitamins in a food complex are superior to USP isolated ones.
Vitamin B1, Thiamin The free vitamin B1 (called thiamin) is a base. When it is synthesized it becomes a solid salt such as thiamin hydrochloride or thiamin mononitrate . Synthetically thiamin is usually marketed as thiamin hydrochloride or thiamin mononitrate  and is a made from Grewe diamine (a coal tar derivative ) processed with ammonia and other chemicals . No thiamin hydrochloride (often listed as thiamin HCL) or thiamin mononitrate is naturally found in food or the body (thiamin pyrophosphate is the predominant form in the body ) . Yeast and legumes are excellent food sources of natural thiamin . "Thiamin is rapidly destroyed above pH 8...the addition of sodium bicarbonate to green beans and peas to retain their color or to dried beans to soften their skins inactivates thiamin" . High heat, x-rays, and UV irradiation also destroy thiamin [9,10]. Thiamin mononitrate tends to be used for food fortification since it is more stable under storage and processing conditions . An animal study found that a natural food complex vitamin B1 was absorbed 1.38 times more into the blood and was retained 1.27 times more in the liver than an isolated USP thiamin hydrochloride .
Vitamin B2, Riboflavin The free vitamin B2 (called riboflavin) is a weak base. When synthesized it becomes an orange amorphous solid . Some synthetic riboflavin analogues have very weak vitaminic activity . Some natural variations, especially in coenzyme forms, occur in plant (including fungal) species . One study found that the pasteurization of bovine milk seems to reduce the bound form of riboflavin from 13.6% to 2% . An animal study found that a natural food complex vitamin B2 was absorbed into the blood and was retained 1.92 times more in the liver than an isolated USP riboflavin .
Vitamin ‘B3’, Niacinamide "Niacin is a generic term...the two coenzymes that are the metabolically active forms of niacin (are)...nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP)...Only small amounts of free forms of niacin occur in nature. Most of the niacin in food is present as a component of NAD and NADP...nicotinamide is more soluble in water, alcohol, and ether than nicotinic acid...many analogues of niacin have been synthesized, some of which have antivitamin activity " . Niacinamide (also called nicotinamide) is considered to have less potential side-effects than niacin ; it also does not seem to cause gastrointestinal upset or hepatotoxicity that the synthetic time-released niacin can cause . Beef, legumes, cereal grains, yeast, and fish are significant natural food sources of vitamin B3 . Processing losses for this vitamin are mainly due to water leaching . Synthetic niacin is usually made in a process involving formaldehyde and ammonia . An animal study found that natural food complex niacinamide is 3.94 times more absorbed in the blood than USP niacinamide and 1.7 times more retained in the liver than isolated USP niacinamide .
Vitamin ‘B5’, Pantothenate Pantothenate was once known as vitamin B5 . USP "Pantothenic acid consists of pantoic acid in amide linkage to beta-alanine", but the vitamin sometimes referred to as B-5 is not found that way in nature . In food it is found as pantothenate; foods do not naturally contain pantothenic acid . "Synthetic D-pantothenate, the active enantiomer is available as a calcium or sodium salt. However, multivitamin preparations commonly contain its more stable alcohol derivative, panthenol" . Producing synthetic pantothenic acid involves the use of formaldehyde . Organ meats, yeast, egg yolks, and broccoli are rich dietary sources of natural pantothenate . Cooking meat and the processing of vegetables lead to significant losses of pantothenate (15-50% and 37-78% respectively) .
Vitamin B6 "An understanding of the various forms and quantities of these forms in foods is important in the evaluation of the bioavailability and metabolism of vitamin B-6"... one of the forms that vitamin B-6 exists is in the form of "5’0-(beta-D-glycopyransosyl) pyridoxine. To date only plant foods have been found to contain this interesting form of vitamin B-6" . Yeast and rice bran contain more natural vitamin B6 than other foods . The most common form in vitamin pills is USP pyridoxine hydrochloride which is not naturally found in food . At least one synthetic vitamin B-6 analogue has been found to inhibit natural vitamin B6 action . Vitamin B6 supports the nervous, skin, and tongue; severe shortages result in abnormal brain patterns and convulsions . Synthetic B6 usually requires formaldehyde in its production  and the extremely high amounts used in some synthetic supplements poses more risk than the lower amounts generally found in food vitamins . An animal study found that natural food complex vitamin B6 was absorbed 2.54 times more into the blood and was retained 1.56 times more in the liver than an isolated USP form .
Vitamin ‘B9’, Folate The vitamin once known as vitamin M (and also vitamin B9 ) exists in foods as folate (also known as pteroylglutamate) . Initially, natural food complex folate was given for people with a pregnancy-related anemia in the form of autolyzed yeast; later a synthetic USP isolate was developed . Pteroylglutamic acid, the common pharmacological (USP) form known as folic acid, is not found significantly as such in the body and appears to be absorbed differently than folate . Folic acid is not found in foods, but folate is . Herbert reports a study found "that consumption of more than 266mcg of synthetic folic acid (PGA) results in absorption of unreduced PGA , which may interfere with folate metabolism for a period of years" . Fortification with synthetic folic acid has been found to increase consumption for those who already have higher dietary intakes of folate more than those with lower intakes . It is believed that fortification with synthetic folic acid may put a portion of the population at risk for vitamin B12 deficiency , yet all grain products advertised as enriched must (according to the US FDA) be fortified with folic acid . "Foods with the highest folate content per dry weight include yeast, liver and organ meats, fresh green vegetables and some fruits" . Food processing is a concern since "50-95% of folate in food may be destroyed by protracted cooking or other processing such as canning, and all folate is lost from refined foods such as sugars, hard liquor, and hard candies" . An animal study found that a natural food complex folate was absorbed only 1.07 times more into the blood, yet was retained 2.13 times more in the liver than isolated USP folic acid .
Vitamin B12 Initially natural food complex vitamin B12 was given for people with pernicious anemia in the form of raw liver, but due to cost considerations a synthetic USP isolate was developed . Cyanocobalamin (the common pharmacological/USP form of vitamin B12) is not found significantly as such in the body; it is usually present in reduced metabolically active co-enzyme forms (without the cyanide) often conjugated in peptide linkage [31,32]. According to Herbert (and others) vitamin B-12 when ingested in its human-active form is non-toxic, yet Herbert and Das have warned that "the efficacy and safety of the vitamin B12 analogues created by nutrient-nutrient interaction in vitamin-mineral supplements is unknown" . Some synthetic vitamin B12 analogues seem to be antagonistic to vitamin B12 activity in the body [33,34]. Synthetic B-12 is made through a fermentation process with the addition of cyanide . An animal study found that a natural food complex vitamin B12 was absorbed 2.56 times more into the blood and was retained 1.59 times more in the liver than isolated USP cyanocobalamin .
Food Processing and Fortification
The primary reason that nutrition became recognized as a separate science was the result of food processing. The refining of brown rice into white rice reduced B-complex vitamins and initially led to deaths in Asia due to beriberi [5,35]. At first beri-beri was thought to be due to an infection, until it was learned that it was due to a lack of B vitamins. Actually, the reason they are called ‘B’ vitamins, is that the B initially stood for ‘beri-beri’. The ‘solution’ to beri-beri was to add synthetic USP vitamins. Even though synthetic USP vitamins are added to white rice and does help prevent beri-beri, this ‘fortified’ white rice does not contain the same nutrients as unpolished brown rice (nor does white flour contain the same nutrients as whole flour) [35,36] and can contribute to other health problems (such as constipation due to lack of fiber). Adding synthetics, most of which are not in the same chemical form as found in food vitamins, forces the body to digest them in ways it never should have to—why add this unnatural digestive stress?
The earlier refining of corn meal which reduced natural vitamin B-3 and amino acid levels was so devastating it produced around U.S. 7,000 deaths per year for several decades . The refining of whole grains (including wheat, rice, and corn) has resulted in a dramatic reduction of their natural food complex nutrients [25,35]. The milling of wheat to white flour reduces the natural food complex vitamin and mineral content by 40-60% . Various food processing techniques (including pasteurization of milk) reduce the available vitamin B6 in foods by 10-50% [35,36]. Irradiation of meat and other foods "changes the characteristics of food"  and has been found to reduce levels of vitamins B1, B6, and other nutrient levels [6,22,37]. Unknown nutrients may also be affected from food processing. No one yet knows how the combinations of these more recent food processing techniques will effect human health , but it is not likely that they will promote optimal nutrition.
In nature, vitamins are never isolated. The primary reason that isolated USP vitamins were developed was cost . A secondary reason probably was standardization (it is harder to standardize food), including stability [1,6,26]. Neither reason justifies placing USP isolates on the same health level as natural vitamins as found in foods.
Studies suggest that the bioavailability of natural food complex B vitamins is better than that of isolated USP vitamins [e.g. 5,12], that they may have better effects on maintaining aspects of human health beyond traditional vitamin deficiency syndromes, and at least some seem to be preferentially retained by the human body . It is not always clear if these advantages are due to the physiochemical form of the vitamin, with the other food constituents that are naturally found with them, or some combination. Regardless, it seems logical to conclude that for purposes of maintaining normal health, natural vitamins are superior to synthetic ones. Eating high dose synthetic B vitamins is like trying to make a computer when you only have 90% of the pieces with many of those pieces being larger than normal size; eating natural B vitamins is like trying to make a computer with 100% of the parts with all the parts the correct size. Which of the ‘computers’ would work better? Obviously the one with 100% of the right parts!
Most people can improve their health by eating health-building whole foods such as fruits and vegetables and whole grains (and consuming less refined carbohydrates) . This alone can help increase the consumption of natural B vitamins. Vitamin B nutrition should come from food or from supplements which are as close to food as possible. Since no one knows everything there is to know about nutrition, it seems logical from both a historical and modern perspective to consume vitamins in the forms found in natural food complexes and not to try to build health based on chemical isolates.
High-Protein Diets - Are You
By: Monique N. Gilbert
Protein is a vital nutrient,essential to your health. In its purest form, protein consists of chains of amino acids. There are 22 amino acids that combine to form different proteins, and 8 of these must come from the foods we eat. Our body uses these amino acids to create muscles, blood, skin, hair, nails and internal organs. Proteins help replace and form new tissue, transports oxygen and nutrients in our blood and cells, regulates the balance of water and acids, and is needed to make antibodies. However, too much of a good thing may not be so good for you. Many people are putting their health at risk by eating to much protein. Excessive protein consumption, particularly animal protein, can result in heart disease, stroke, osteoporosis, and kidney stones. As important as protein is for our body, there are many misconceptions about how much we really need in our diet, and the best way to obtain it.
The average American eats about twice as much protein than what is actually required. Some people, in the pursuit of thinness, are going on high-protein diets and are eating up to four times the amount of protein that their body needs. Protein deficiency is certainly not a problem in America. So exactly how much protein does your body really need? Much less than you think. According to the American Heart Association and the National Institutes of Health, as little as 50-60 grams of protein is enough for most adults. This breaks down to about 10-12% of total calories. Your body only needs .36 grams of protein per pound of body weight. To calculate the exact amount you need, multiply your ideal weight by .36. This will give you your optimum daily protein requirement in grams. Since the amount of protein needed depends on the amount of lean body mass and not fat, ideal weight is used instead of actual weight. Infants, children, pregnant and nursing women require more protein.
People on high-protein diets are consuming up to 34% of their total calories in the form of protein and up to 53% of total calories from fat. Most of these people are unaware of the amount of protein and fat that is contained in the foods they eat. For instance, a typical 3-ounce beef hamburger, which is small by American standards, contains about 22 grams of protein and 20 grams of fat. You achieve quick weight loss on these diets because of this high fat content. High fat foods give you the sensation of feeling full, faster, so you end up eating fewer total calories. However, this type of protein and fat combination is not the healthiest. Animal proteins are loaded with cholesterol and saturated fat. Many people on these diets also experience an elevation in their LDL (the bad) cholesterol when they remain on this diet for long periods. High levels of LDL cholesterol in the blood clog arteries and is the chief culprit in heart disease, particularly heart attack and stroke. So while you may lose weight in the short-run, you are putting your cardiovascular health in jeopardy in the long-run.
Another reason weight loss is achieved on these high-protein diets, at least temporarily, is actually due to water loss. The increase in the amount of protein consumed, especially from meat and dairy products, raises the levels of uric acid and urea in the blood. These are toxic by-products of protein breakdown and metabolism. The body eliminates this uric acid and urea by pumping lots of water into the kidneys and urinary tract to help it flush out. However, a detrimental side effect of this diuretic response is the loss of essential minerals from the body, including calcium. The high intake of protein leaches calcium from the bones, which leads to osteoporosis.
Medical evidence shows that the body loses an average of 1.75 milligrams of calcium in the urine for every 1 gram increase in animal protein ingested. Additionally, as calcium and other minerals are leached from our bones, they are deposited in the kidneys and can form into painful kidney stones. If a kidney stone becomes large enough to cause a blockage, it stops the flow of urine from the kidney and must be removed by surgery or other methods.
Plant-based proteins, like that found in soy, lowers LDL cholesterol and raises HDL (the good) cholesterol. This prevents the build up of arterial plaque which leads to atherosclerosis (hardening of the arteries) and heart disease, thus reducing the risk heart attack and stroke. The amount and type of protein in your diet also has an important impact on calcium absorption and excretion. Vegetable-protein diets enhance calcium retention in the body and results in less excretion of calcium in the urine. This reduces the risk of osteoporosis and kidney problems. Interestingly, kidney disease is far less common in people who eat a vegetable-based diet than it is in people who eat an animal-based diet. By replacing animal protein with vegetable protein and replacing saturated fat with unsaturated fat, like that found in olive and canola oils, you can avoid the pitfalls of the typical high-protein diet. You will be able to improve your health and regulate your weight while enjoying a vast array of delicious, nutritionally dense, high fiber foods. Remember, eat everything in moderation and nothing in excess. Also, the only healthy way to achieve permanent weight loss is to burn more calories than you take in. Anything else is just a gimmick.
To learn more about the health benefits of soy, visit the Virtues of Soy website at: http://www.virtuesofsoy.com
Monique N. Gilbert is a Health Advocate, Recipe Developer, Soy Food Connoisseur and the author of "Virtues of Soy: A Practical Health Guide and Cookbook" (Universal Publishers, $19.95)
Application of Genomeceuticals
By: Mark Brudnak, B.S., N.D., Ph.D.
Autism is a developmental disease affecting as many as 1 in 300 children and is often characterized as a mental disorder originating in infancy that is associated with self-absorption, inability to interact socially, behavior and language dysfunction (e.g. echolalia). Current theories indicate an important role of diet in the development of disease. It is thought, that as a result of maldigestion of casein and gluten, opioid-type peptides, or exorphins, are produced. Additionally, because of the time-frame of development of the disease there has been an association with childhood vaccination. Consequently, prevailing therapies attempt to address these causes in one or a combination of three ways: diet restriction (removing casein and gluten); supplementation with exogenous enzymes; and probiotic bacteria. Until recently, none of the therapies addressed the molecular mechanisms that may be at work in the development and progression of autism. This paper presents potential molecular and cellular mechanism related to autism as well as discusses their application to the treatment of the disease through the application of genomeceuticals. Additionally, a link between developmentally associated aberrant immune and inflammatory responses, and autism is suggested and explored. ã 2001 Harcourt Publishers Ltd
The etiology of autism can be, in large part, explained as the result of a combination of aberrant immune responses and genomic regulatory events. The persistent yet varied nature of the symptoms suggests that molecular switches are thrown early in development, which are never completely restored to proper functionality. Possible molecular and cellular events surrounding autism are discussed below along with suggested future experiments. Additionally, a potential therapy, based on the data, is offered.
It has been estimated that 5:10,000 (1) to 1:300 children suffer from autism, with an initial manifestation of symptoms by age three. While the exact cause of autism remains elusive, considerable advances have been made in recent years. These advances originate from a study of the geographic localization, and biological and psychological aspects of the disease. From these studies, several theories have emerged.
One such theory is that autistic children suffer from several maladies with the accumulated symptoms being classified as autism. Here, the autistic child's digestive tract is thought to function suboptimally. During digestion, pre-opioid type compounds in the diet, typically from casein and gluten, are thought to be activated because of an incomplete breakdown of proteins (2). These exorphins (i.e. casomorphins and glutemorphins) are then easily transferred across the lumen of the gut into the circulation where they exert opioid-type action on the brain. The transfer of peptides across the lumen of the gut is thought to occur at high levels due to the 'leaky' nature found to be associated with the autistic's gastrointestinal tract.
Different approaches have been employed to rebuild proper functioning of the autistic child's gut with regard to both absorption and digestion. Of these, enzyme therapy and probiotic supplementation have been favored and have met with a degree of success. Enzyme therapy has typically been based on supplementation with large amounts of proteases from the different categories of proteolytic enzymes and these have included acid or carboxyl peptidases, serine, cystein and zinc proteases. Additionally, peptidases with both endo- and exopeptidase activity have been favored.
Probiotic supplementation has focused mainly on trying to rebuild the intestinal wall via a restoration of the naturally occurring bacterial flora. Two approaches to the treatment of autistic dysbiosis using probiotic cultures have emerged. The first uses a wide variety of organisms and is something of a 'shotgun' approach, The second employs a more target oriented approach by supply very large numbers of viable organisms, as high as 100 billion/g. Both approaches have been based on clinically observed and published therapeutic benefits of probiotics and have met with a degree of success.
More recently, a genomeceutical (3) approach has been introduced (4). Genomeceuticals are naturally occurring compounds, which are able to affect gene expression, Genomeceutical theory has led to the inclusion of galactose in at least one enzyme formula. The inclusion of galactose in the formulation is based on three different scientific papers. The first was the report by Smith et al. (5) that galactose can increase the expression of dipeptidyl peptidase-IV (DPPIV or CD26) in marine (mouse) enterocytes. The enterocytes are the cells that line the lower gastrointestinal tract. The second is based on the finding that adding the glucosamine, could increase the level of transcription and translation (6). Both are important for a nutrient to be able to affect the levels of a protein made from the DNA. Wang's work demonstrates clearly, elegantly, and definitively, that the concept of genomeceuticals is sound. By adding glucosamine to the diet, not only did they get more RNA, but they got more protein as well. The corollary is that, by adding galactose, more DPP IV can be made. The third work is based on Brudnak's observation that because the addition of glucosamine to a diet can increase the expression of leptin (fat hormone) in the body the addition of galactose may have a similar effect on DPPIV (3).
Genomeceuticals describe nutrients which can affect the structure of a gene, how well the gene products (protein and sometimes RNA) work, and/or how much of it is made. That is to say, genomeceuticals cannot just replace substances, which may be missing (e.g. an enzyme diminished by mutation), but actually alter the expression and functionality of gene products in, and resulting from, genomic multilevel nutrient-sensing pathways. The last category is where the inclusion of the galactose comes into play. In this case, the genomeceutical would be galactose.
Galactose appears to be able to increase the expression of the dipeptidyl peptidase IV gene. This means adding galactose can increase the amount of DPP IV that is present. If, in autistic children, the situation is not that there is absolutely zero DPP IV made, because of a mutated gene or regulatory element, but rather that the gene has been silenced or 'turned down' (down-regulated), then the addition of galactose has the potential to reverse or circumvent that, the caveat being that the gene needs to at least be functional and this is discussed below. Indeed, DPP IV has been shown to be down regulated in autistic children and is currently being used as a diagnostic marker for the disease. However, that is not the only place DPP IV, and DPP IV-like enzymes are expressed and may prove to be secondary to other sources. Those other sources are the peripheral blood cells and are discussed below.
Regardless of the effectiveness of galactose to increase enterocyte production of DPPIV, the stage is set for further investigation, prevention and therapeutic exploitation of the molecular mechanisms involved in autism. Enterocyte gene expression may be of secondary importance to the immune system. The way in which events at the genetic level translate to cellular interactions and eventually to an autistic condition is the subject of this paper. It is suggested herein that the gut-associated lymphoid tissue (GALT) is a major contributor to the pathological manifestations of autism. Through molecular mechanisms occurring early in development, possibly due to a vaccine sensitization or mycobacterium infection, genomic regulation goes awry and leads to malfunctioning immune and gastrointestinal systems. The rationale for the molecular and cellular events suggest is discussed below. Additionally, experimental data are presented for strong support of the importance of the caveats discussed. Such caveats suggest that, while some natural compounds may indeed prove beneficial in stimulating the immune system of the autistic, great care must be taken in the selection of these agents so as not to introduce potentially mitogenic, mutagenic, or cytotoxic agents such as lectins.
MATERIALS AND METHODS
To test the ability of lectins to kill mammalian cells, seven concentrations of lectin were tested, each in triplicate. BW5147.3 cells (thymocytes) were grown to mid logphase in RPMII640 media supplemented with L-glutamine, antigen presentation is accomplished through interaction with the TCR. The bound TCR then transduces a signal to the nucleus directing an altered expression pattern, which includes QPP. QPP is then secreted into circulation and is free to digest any exorphins present. Glucans have also been shown to upregulate transcription factors in the cell nucleus (16). Adding b glucan into the system can alter the expression of genes in a secondary cell. Thus genomic multi-level functionality of nutrients is the hallmark of a genomeceutical. Importantly, b glucans have been shown to confer protection against mycobacterium (l7). It should also be noted that cellular signal transduction across the cell membrane is often associated with G-proteins and this may explain, at least its part, recent observations of the relationship between vitamin A and autism (18).
RESULTS, FUTURE DIRECTIONS, AND CAVEATS
Beta glucans are certainly not the only compounds that can stimulate a TCR. In fact it is well known that antibodies and lectins can do the same. However, adding the former, with high enough specificity, is not practical within a nutritional approach. Similarly, there are problems with the latter. Recently, products have shown up in the US market that claim to block sugar absorption. These products contain relatively large (sometimes hundreds of grains) amounts of kidney bean (Phaeolus vulgaris) extract. Legumes in general are known to contain large amounts of lectins. Lectins are a class of nonimmune, nonenzymatic glycoproteins that specifically bind sugars. In this case, the lectin is called PHA. PHA is a tetramer existing either as a homo-or heterotetramer consisting of two different subunits and is given the designations ‘-L’ or ‘-E’ depending on the ratio of the subunits.
In addition to the ability to bind sugars at low levels, lectins are also used as potent mitogens in the laboratory. Lectins are also efficient mutagens at higher levels. At even higher levels, lectins become cytotoxic. It is usual to use cytotoxic lectins, such as PHA, to create and select mutants in the laboratory. The levels required to achieve these effects are not nearly as high as those that can be achieved with supplementation, in localized microenvironments, the concentrations achieved could be extremely high.
Figure 1 (shown below) shows a typical killing curve employing PHA-L against thymocytes. As can be seen, cell death results at very low concentrations of the lectin. At just 20 ug of lectin, a 30% lethality is observed. In fact, the concentrations of the lectin shown in Figure 1 are much lower than those that might be obtained from the ingestion of the purported sugar absorption blockers. At the very least, the sugar absorption blockers could often achieve mitogenic or mutagenic concentrations. The mode of action of lectins to cause cell death is not well understood, but is generally believed to be the result of a signal transduction to the nucleus of the cell in the nucleus, the DNA then directs the cell to undergo a form of apoptosis. Similar to antibodies, the ability of lectins to bind to a TCR is what makes them so lethal in vivo.
It is anticipated that more nutritional compounds, able to directly stimulate cells to produce QPP, will lie uncovered. Even a cursory review of the literature suggests several options (19,20). It should be relatively straightforward to screen compounds for this sort of activity. T cells are routinely cultured along with macro phages. One could easily set up experiments where varying concentrations of the test nutrient are added to tissue culture cells, The cells would be cultured for an appropriate period of time and quantitatively assayed for both RNA (via PCR) and protein (protein gel) expression. These are reasonably straightforward experiments whose results would have vast potential.
As can be seen, there is at least preliminary evidence that suggest a connection between autism, infection, and vaccination. Such a situation is easily envisioned as bacterial or mycobacterial. One possible scenario is a mycobacterial infection early in development. The immune system is not fully functional at this point. However, the GALT is and initiates a response. Proteolytic genes are turned off, cytokines associated with infection and inflammation (the exact role of these is still unclear but there appears to be a connection) are secreted. The secretion of the cytokines may prove to be a key 'autistic switch'. Perhaps the status of the switch may he monitored by the ratio of IL2 to IL10, which tends to be indicative of a cell-mediated (delayed type hypersensitivity) or a humoral antibody response, respectively. Subsequent to infection, affected gut tissue is encouraged towards apoptosis. A leaky gut results, which is never fully repaired, as the genes required by the lymphocytes for this have been downregulated. The cycle continues and may even be aggravated as repeated infections are incurred. Additionally, antibiotics, which are known to inhibit exorphin digesting enzymes (DPP IV) may be employed resulting in a worsening of the condition.
While the above scenario is speculative and incomplete, it does explain many of the facets of autism. Most prominently, it offers an explanation as to why there has been such a dramatic increase in autism in recent years. With the advent and implementation of vaccination programs in developed countries, there appears to have been a concomitant increase in autism. Offered here is one explanation of how such vaccines, in addition to infections, might be acting to alter the functionality of the converse is also true. That is to say, if the genes are not needed, they then are switched off and when they are needed, in cases where an abundance of inhibitor has been introduced, the genes are turned on.
It has been suggested that the IEL population has evolved to recognize epithelial-cell alterations outside the basement-membrane barrier. Adulteration of these surveillance cells results in an opening of the body's first line of defense against foreign antigens. IELs, upon exposure to foreign antigen, undergo molecular and cellular changes. Gene expression patterns are notably altered as evidenced by a shifting cell-surface architecture (10).
Recently, a new peptidase (quiescent cell proline dipeptidase or QPP) from peripheral blood mononuclear cells (PBMCs) has been cloned and investigated (11,12). QPP is structurally and functionally related to DPPIV but is found in the peripheral blood cells. Interestingly, QPP shares little sequence homology with DPP IV. These enzymes are among the few that have the ability to cleave proline-containing peptide bonds. As mentioned above, both opioid type peptides contain proline and are resistant to degradation as smaller peptides. Whereas DPP IV is thought to degrade chemokines and quench an immune response, no function has been attributed to QPP. However, it has been observed that inhibitors of post-proline cleaving aminopeptidases can cause apoptosis in quiescent cells. It is worth noting, that inhibitors of DPP IV (7) have been shown to downregulate expression of the DPP IV gene (14). This demonstrates that the DPP IV gene is sensitive to environmental signals. While not specifically examined yet, it is reasonable to suspect similar cell death of enterocytes upon exposure to inhibitors. As stated above, there are competitive inhibitors of aminopeptidases and they may have an effect of cells expressing such enzyme. It is possible that via early exposure to vaccines, the enterocytes and other gut-associated cells arc encouraged towards apoptosis. The resulting cell death may account for the 'leaky' nature of the autistic's gut as well as the other symptoms of dysbiosis. Because apoptosis is dependent on molecular biological alterations in the genome, surviving cells may indeed have been altered, just not to the point of actually causing cell death. In fact, the altered expression pattern of DPP IV reported for autistic is evidence that this is indeed the case.
For all intents and purposes, no enzyme digestion in the body is ever 100% complete. Statistically, some protein or peptide fragments will escape the digestive process and be absorbed. The larger fragments may be transferred across the lumen of the gut via the M-cells and active transport, whereas the smaller fragments may simply diffuse. Couple to that fact the leaky gut of an autistic child, and it is easy to see how biologically significant quantities of peptides or, more precisely exorphins for the purpose of these discussions, can enter the circulation. As stated previously, a novel method for dealing with this is to increase the level of DPP IV produced by the enterocytes by the addition of galactose. However, there may still be opioid peptides, which reach circulation. How then can these circulating exorphins best he handled? Exploitation of the QPP gene is the logical next step. If the QPP gene can be upregulated, then any exorphins that do manage to survive across the lumen of the gut, will have an increased chance of being digested once inside the circulatory system.
Because it is expressed in, and secreted from, the peripheral blood cells and not just in enterocytes, there is an added opportunity to employ the properties of genomeceuticals. That is to say, if circulating lymphocytes were able to be stimulated to produce more QPP, this should in turn assist the ex post facto (from the view of absorption) digestion of peptides that make it into circulation. Indeed, studies are currently under way to decipher the molecular mechanism regulating QPP expression. At the present time, however, there are already preliminary data to show that stimulation of the TCR causes an upregulation of the QPP gene. This opens the door to therapeutic intervention via the QPP gene if a suitable stimulator of the QPP gene can be found.
As previously stated, the TCR can be stimulated by a number of currently well-know factors. These include, but are not necessarily limited to, antibodies, lectins, and macrophages. While certain natural and potentially safe lectins (13) may exist and be shown to be useful in the future, current technology makes mammalian lectins impractical. Also, as shown in the data, plant lectins can be extremely dangerous. Antibodies offer some potential, but there are also many problems associated with their use. These include everything from their ethical production to safety. Encouragement of macrophage participation solves most of the problems and presents an opportunity for therapeutic application of genomeceuticals.
It is well known that, in the gut, cellular components of bacteria, fungi, and molds can stimulate the gut-associated macrophages. These macrophages constantly sample and survey the gastrointestinal tract for foreign antigens. The cellular components responsible for the stimulation the macrophages have been well documented and include not just proteins, but carbohydrates such as the b glucans present in cell walls of microorganisms (l5). When macrophages are exposed to b gluons, such as the yeast cell wall b-1,3/1,6-glucan, they become non-specifically stimulated so that subsequent antigen exposure results in a much more robust immune response than would otherwise occur. Among those responses is the secretion of cytokines, and the processing and subsequent presentation of antigens to T-cells. That role of penicillin (50 units/ml), streptomycin (50 ug/ml) and 10% heat inactivated calf serum. Cells were resuspended in media and counted via Trypan Blue exclusion method. An appropriate dilution was determined so as to place 1 x 104 cells/well in a 96-well microtitre plate using 100 ul/well. The pectin PHA-L (Vector) was diluted in media so as to make the final concentration in the well 0,5,10,20,40,100, and 2 for three days and then pulsed for 24 h with 2 uCi/ml, 50 umol of [3H)dThd. Cells were harvested on to Whatman GF/C filters, dried under UV light for 1 hour, and placed into individual scintillation vials containing 7 ml of scintillation fluid. Radioactivity was determined by counting on a Beckman LS 3801 gated for 3H Figure 1 lists the results. The procedure was then duplicated for verification (data not shown).
Fig. 1 BW5147.3 cells (thymocytes) were grown to mid log-phase in RPMI1640 media supplemented with L-glutamine, penicillin (50 units/ml), streptomycin (50 ug/ml) and 10% heat inactivated calf serum. Cells were resuspended in media and counted via Trypan Blue exclusion method. An appropriate dilution was determined so as to place 1 x 104 cells/well in a 96-well microtitre plate using 100 ul/well. The lectin PHA-L (Vector) was diluted in media so as to make the final concentration in the well 0,5,10,20,40,100, and 2 for three days and then pulsed for 24 h with 2 uCi/ml, 50 umol of [3H]dThd. Cells were harvested on to Whatman GF/C filters dried under UV light for 1 hour and placed into individual scintillation vials containing 2ml of scintillation fluid. Radioactivity was determined by counting on a Beckman LS 3801 gated for 3H. The procedure was then duplicated for verification (data not shown).
As stated above, cases of autism present early in development. Typically, a diagnosis of a psychological dysfunction is perplexingly suggested as both the result and the attributed cause. Because autistic symptoms present early in development, researchers have suspected a link with childhood vaccinations. However, no clear mechanism for this has been presented and tested. The glaring insufficiency in all the arguments is a failure to explain a continued manifestation of the symptoms of autism, other than permanent brain damage occurring early in development. Because of the fluctuating nature of the symptoms (some children get worse and some better over time), and hence attempts to link them with diet, it is generally suspected that brain damage does not complete the story. However, some hints are suggested upon examination of the immune system.
Historically, the immune system has been thought to develop early in life through education of the cellular components within the thymus (T-cells) and spleen (B-cells). There, the various cells are trained to recognize self vs non-self antigens and to take the appropriate action, or lack thereof, in response to any exposure. However, in the last decade, a new class of immune cells has been intensively studied. These cells never 'see' the thymus or spleen and are educated solely in the intestinal tissues from which they arise. These intraepithelial lymphocytes (IEL), or 'intestinal' epithelial lymphocytes, are an athymically derived T-cell subset expressing the gd TCR-CD3 complex along with CD8. The gd T cells in the epithelial tissues do not circulate as their ab T cell (thymically derived) relatives do.
While great strides have been made in understanding the nature of the antigens the IELs recognize as well as their function, much of the picture has remained elusive (8). Similar to antibodies, the gd TCR has a broad specificity and binds both nonpeptides as well as peptides. This binding is required for initiation of an immune cascade resulting in cytokine release and colonal expansion. The termination of the cascade then results from suppressor cells. Additionally, antibodies and lectins have been shown to bind and stimulate the T cell through the TCR.
Though the subject of much speculation and heated debates, the IELs are thought to be a primordial immune system and the first to function in life. IELs have been shown to bind to mycobacterial antigens that are protease resistant and appear to have been selected to respond quickly to unique immune challenges. Interestingly, the proteins recognized on mycobacteria are related to the heat-shock proteins found in all organisms, including humans. Because the proteins are protease resistant, the associated immune cells responsible for their removal would not benefit from an increased production of protease genes. In fact, the immune cells would evolve to conserve energy and redirect efforts by turning off those protease genes. Those that would be down-regulated might include DPP IV and other similar genes. In fact, a search of several heat-shock protein sequences revealed no potential proline-specific catalytic sites. It has been noted that the amount of DPP IV can actually increase in the pretence of a known inhibitor (9). This is reasonable given the above argument that the immune system in such a way as to also depress the body's ability to cope with dietary opioid-type compounds. That is to say, there is a feedback mechanism, possibly a form of tolerization, resulting from large doses of foreign protein during immunization, which causes an altered regulation of key genes required for proper functioning of the immune and digestive systems during a pivotal developmental period. Additionally, it points the direction for future research. It is known there are gene loci associated with autism (21) and these need to be explored in the context of not just the molecular biology but the cellular immune system as well. With the emergence of a human genetic map and sequence, the study of these aspects will be greatly facilitated and is sure to advance rapidly.
Issues Beyond Tissues
By: Asad Shahsavari, NMD, PhD, MD (MA)
Today's medical mentality isreinventing the healing wheel from traditional and shamanic modalities to sophisticated technology and chemical wizardry. Yet, there is more to medicine than doctoring and many more issues than tissues in dealing with the art of healing. Reducing a human being to a purely biological creature with tunnel vision toward calculated structures and pre-destined genetic codes is to disgrace millions of years of human development beyond biology. The myriads of life cycles throughout these millennia have left memories, instincts and imprints of consciousness on the human psyche. Conventional medicine has a tongue-in-cheek attitude toward these psycho-spiritual aspects of health and often demote them to personal growth seminars and psychic hotlines. And, yet, who among us would be content at experiencing life on the level of an amoeba or a rutabaga? Is medicine missing the mark? What are the loopholes in the complex reordering of metabolic chaos from rearranging genes to realigning one's entire perspective on being alive?
Perhaps the personal care and individualized treatment protocols of naturopathy and other alternative medical therapies bring to light a most important aspect of healing itself. That of process. Process is paramount. Process is the character of the therapy. It personifies the healing by expressing its parameters in terms of boundaries of acceptability and issues of compatibility and dignity. The processes involved in healing should include those of the same quality and dynamic as those in developing a deep relationship, which is lasting and meaningful. Kindness, compassion and lovingness have their counterparts in healing modalities.
Relationships are the centerpiece of our lives. We grow up in families, have circles of friends, establish working associates and create deep connections with life partners to come full circle again back to the core relationship of the family unit. Yet, the most critical relationship, that of how we relate to our local selves and our higher self, is at the foundation of why we survive or why we don't. Genetic engineering can do little to change one's sense of self esteem and enlightenment, as these are not engineered, but earned as a result of self-determination and fulfillment.
Healing is a process of acknowledgment, acceptance and action. One must recognize the imbalances and intrinsic causes of illness in order to arrive at a point of reconciliation with trusting the body's innate healing mechanisms and the psyche's intuitive senses of survival. As one puts into motion activities which are directed toward living principles such as nutrition, exercise, meditation, hygiene, creative experiences and spiritual reconnections, the process of healing rekindles a mind set which is common ground to the whole of human evolution. Each of these is an activity that requires intimate personal involvement. Perhaps that is one of the missing links in modern medicine's broken chain of command in eliminating the saga of human illness.
The patient is viewed as another genetically-bred animal. Their fears, inhibitions, challenges, hopes, dreams, belief , weaknesses and strengths are basically ignored in favor of blood tests, x-rays, empirical studies and randomized trials. As if a day in the life of anyone is ever a laboratory-controlled experiment. Medicine divorces a patient from their own sense of life. They start focusing on the illness, treating the illness, living the illness and dying from the illness. If more emphasis were placed on life-regeneration than disease-degeneration, perhaps more people would create cures to their scrambled existences and mend the wounds of their lives. Why should healing be any different than living?
The emotional and Psycho-spiritual components of humanity are often side-stepped or overlooked by conventional medicine. Emphasis is placed on the treatment protocols rather than the patient's prime importance as the healing agent. Often a patient is overwhelmed with fear, intimidation and caustic chemicals and procedures. In such cases, the rationale behind the medicine may not be its rational nor as effective as one would hope. And yet, hope, the major marker in miraculous healings, is seriously downgraded and too often destroyed. With the multitudes of "advancements in medicine" largely attributed to the complex machinery and arsenal of wonder drugs, unfortunately the number one killers in America, heart disease and cancer, continue to claim millions of lives annually. It appears that these so called advancements in medicine have little to do with advancements in healing.
Despite extensive medical research projects and the HMO take-over of American medicine, more and more people, at even younger ages, are experiencing debilitating and life-threatening problems. Mental disorders are on the rise with depression, anxiety and attention deficit leading the pack. The anti-depressant Prozac is one of the leading drugs sold worldwide and Ritalin (once a common street drug) is administered to over 8 million American children annually. Where we have declared a war on drugs in our neighborhoods we have encouraged drug addiction in our medicine cabinets. The more dependent we become on exterior medicines, the more removed we are from the premise of health, which is wholeness, oneness and a return to self-propriety. Re-establishing the vital relationship with one's self and one's surroundings cannot be achieved through abandonment and addiction. Drugs isolate us from taking responsibility for our health and making executive decisions as to how and why we live. There are certain times when drugs and invasive treatments prove necessary. These should be regarded as the last method of choice, not the first line of defense.
Documented reports in both Canada and the US reveal an astounding 100,000 iatrogenically-induced deaths per year attributed to prescription drugs. According to experts, that's the equivalent of a jumbo jetliner crashing every day. And yet, the headlines and the news reports reveal nothing of these tragic statistics, allowing us to assume those deaths are caused from an illness rather than a treatment. Rarely is a patient fully apprised of the true dangers of a toxic drug regimen or an irreversible surgical procedure. Everything from mammography to angioplasty, mercury-amalgam fillings to radio active implants, Procardia to Prozac, conventional medicine continues to negate the natural healing process with non-nutritive substances, a lack of preventive measures and an ignorance toward the psycho-spiritual reality of each patient's existence.
With Dr. Dean Ornish’s remarkable landmark study on reversing heart disease with no drugs and no surgery and the subsequent underwriting of his program by forty major insurance companies, nutrition, meditation and supportive relationships have made medical history. Dr. Ornish is currently embarking upon a similar study with prostate cancer. Perhaps, the results will show once again that medicine without medicine is where the true healing is. And the natural healing process will be vindicated and validated.
Just what are the issues beyond tissues in healing which are so easily dismissed by conventional practices? To begin with, each person responds to stress in very unique ways. Just as ages, faces, body types and blood types vary, so do metabolisms, genetics, psychological dispositions and emotional sensitivities. There are countless influences which affect the development of illness and wellness. From cultural, social and religious belief systems to gender, age, and racial biases, there are deep conditionings which are clearly evidenced in our responses to "getting sick or getting better." And, even though modern medicine appears impressive in emergencies, prevention and regeneration are not the prime directive. Ever eager to resect or replace organs, but not to rejuvenate them. Ever willing to experiment with the latest technology or the newest wonder drug, but not considering the basics and common sense of educating health, rather than medicating disease. With 65% of the American public currently using alternative therapies, it is apparent that natural methods are on their way to becoming the standard rather than the alternative.
Then there is the issue of the true provocateurs of illness. Is it the germ or the environment? Is it evil spirits or alien abductions? Pick your poison, pick your weapons, and enter conventional medicine. The old battle between French researchers Louis Pasteur and Claude Bernard appears to have never ended. Although, Pasteur on his death-bed conceded, "Bernard was right. It is not the germ, but the environment in which it lives." Ironically, 100 years later, modern medicine is still waging a war against germs, viruses and the like, with stronger and stronger chemo-weapons all of which suppress the integrity of the environment of the immune system, nature's peace-keeper in the metabolism. Rings a bell as to the futility of war tactics on any level. And what do we know lowers immunity? Poor nutrition, environmental toxins, drugs, and, oh, yes, STRESS, STRESS, STRESS. Not a lack of Prozac or penicillin., but a lack of harmony and balance. Rather like a good piece of music, the immune system tunes itself to the rhythm of a harmonious lifestyles And that, my friends, you cannot buy in a bottle.
It is a dangerous precedent to declare that the sacred domains of the body and psyche are to be controlled by a medical hierarchy. If we do not protect our freedom of medical choice and redefine the parameters of healing modalities, we may as well incarcerate our mothers for ever having given us a kiss to cure a wounded knee or having administered a special soup to take the ache away. When medicine became the most lucrative industry in the western world after WWII, it lost its humanity. It became a genetically engineered giant of synthesized parts and robotic protocols. It hid behind empiricism and clinical trials, convincing us all we were purely statistics and hypothetical textbook creatures. Somehow we bought into the theatrics of it all and became the new guinea pigs eager to take a pill for every ill.
Medical ethics and the accelerated marathon toward genetically engineered perfection may leave us at odds with the singular survival issue we face each moment: What is our mission directive in this life and what are we doing to achieve it? Until each of us comes to terms with our inner beings, our goal, our dreams, our inspirations, we will continue to go from doctor to drug, ever unfulfilled. Only when we open our hearts and minds to the principles of life and the preservation of its sanctity, will we know the gift of the healing spirit that lives within us all.
Asad Shahsavari, NMD, PhD, MD (MA) Director, BIOMED Holistic Health Centers San. Jose & Orangeval , CA 408-374-6133 / 916-990-0505 email: email@example.com
The views and opinions expressed in this online newsletter are not necessarily those of the American Naturopathic Medical Association, its officers or its members, nor are they necessarily in accordance or agreement with its policies.