Industry News
Feature Articles
Bio-Identical Hormone Replacement Therapy Under Attack: Update
Jeff Morris
As we reported in February, the ability of pharmacies to compound bioidentical hormones is at risk as a result of a “citizen petition” filed with the FDA last October by Premarin and Prempro manufacturer Wyeth (Madison, NJ). At that time we noted that there was a grassroots effort to mount opposition to the Wyeth petition, and that the International Academy of Compounding Pharmacists (IACP) had made informational resources available on its Web site.
The FDA initially set an April 4 deadline for public comment on the petition, and we expected that we would now be able to tell you about the outcome of the process. That, as it turns out, is not the case.
To read more, click here
First line comprehensive care (FLCC) of chronic autoimmune diseases:
Integrative approach to causes rather than symptomatic consequences.
Russell Jaffe, M.D., Ph.D.
Part 2 of 2 (continued from last month)
Functional, comprehensive, autologous, ex vivo immune system measurements
Only a functional lymphocyte cell response assay (in contrast to a chemical detection of the presence or absence of an antibody without knowing its physiologic beneficial or harmful function) that is comprehensive (in measuring all delayed allergy mechanisms) can give us information on all these sources of immune reactions.
To read more, click here
Cellular Aging Clocks: Reversing Time’s Arrow With Tetrahedral Spin Chemistry
Todd Ovokaitys, M.D.
Transcending the biological aging process – slowing, stopping, and even reversing it – is likely to be found at the level of DNA chemistry. Recent research suggests that all the proposed mechanisms of aging have as a final common pathway discreet structural changes in DNA. The ability to intervene in these changes and recreate the structures of earlier physiologic age is now an achievable feat that may mark the birth of increasingly powerful rejuvenation technologies.
To read more, click here
Talking to Your Patients & Colleagues about DHEA
Alan P. Mintz, M.D., CMO, CEO
Cenegenics® Medical Institute
Dehydroepiandrosterone (DHEA) is a member of the steroid hormone family that is produced by the zona reticularis of the adrenal cortex in response to pituitary ACTH stimulatory signaling. It is the hormone that is present in the greatest abundance in circulation. DHEA levels peak at around age twenty, and then decline by approximately ten percent per year, with great individual to individual variability. By age 70, DHEA levels reach a relatively stable trough level of 10-20 percent of its young adult levels.
To read more, click here
Cultural Stress: Neuroendocrine-Induced Physiological Aberrant Remodeling—the Modern Pathophysiological Phenotype
Ron Shane, Ph.D.
Abstract
The psychological community once regarded cultural stress as being problematic in a cognitive context, and some theorists have argued that it was the etiological basis for a variety of affective disorders. Moreover, molecular-oriented neurobiologists realized that an allostatic upregulation of the hypothalamic hormone CRF negatively impacts the majority of an organism’s homeostatic physiological processes, as well as its optimal morphological nature. Chronic upregulation of cortisol dramatically alters the transcriptional activities of all of the cells in the body, drastically changing their set points, which transduce specific genetic networks to produce a matrix of tropic factors that significantly modify or structurally remodel the organism’s macrocellular systems. Thus, the overall phenotypical gestalt of the organism is pathologically altered in terms of is physiological dynamics and heuristic structure. Modern man’s cultural strategies have not only unfavorably changed the body’s myriad of physiological systems, but have also aberrantly modified the dispositional sentient nature of the human organism.
To read more, click here
Industry News
Botox, Get Ready for a Rival
Cosmetic maker Medicis teams with a European company to develop and market a competing anti-wrinkle treatment
Reloxin Agreement Between Ipsen and Medicis Becomes Effective
Facial cosmetic medicine maker Medicis Pharmaceutical said it struck a deal with French drug manufacturer Ipsen Promesses to develop and market Reloxin, a potential competitor to blockbuster drug Botox.
To read more, click here
Estrogen Therapy Doesn't Cause Breast Cancer: Study
But treatment isn't risk-free, so women should consult their doctors, experts say
Estrogen therapy on its own does not increase the risk of breast cancer in postmenopausal women, an extensive new study has found.
The findings, from the Women's Health Initiative (WHI), stand in stark contrast to previous results from the estrogen-plus-progestin arm of the trial. That study was halted in 2002, three years ahead of schedule, when evidence showed a higher risk of not only breast cancer, but blood clots, stroke and heart attack.
To read more, click here
Hormone Can Predict Pulmonary Hypertension, Risk of Death
BNP serves as a marker in people with serious lung disease, study says
Robert Preidt
Levels of a hormone called brain natriuretic peptide (BNP) can predict the presence of pulmonary hypertension and the risk of death in people with serious lung disease.
That's the conclusion of a German study in the April issue of the American Journal of Respiratory and Critical Care Medicine.
To read more, click here
Dramatic Changes in U.S. Aging Highlighted in New Census, NIH Report
Impact of Baby Boomers Anticipated
The face of aging in the United States is changing dramatically -- and rapidly, according to a new U.S. Census Bureau report, commissioned by the National Institute on Aging (NIA). Today’s older Americans are very different from their predecessors, living longer, having lower rates of disability, achieving higher levels of education and less often living in poverty. And the baby boomers, the first of whom celebrated their 60th birthdays in 2006, promise to redefine further what it means to grow older in America.
To read more, click here
Tests Predict Long-Term Kidney Risk
Blood, urine screens can spot the dangers decades early
Robert Preidt
Simple blood and urine tests in middle age may help predict a person's risk of developing end-stage kidney disease over the next 25 years.
U.S. researchers say the tests include the urine "dipstick" test (which detects protein in urine) and a blood test to estimate kidney function called the "estimated glomerular filtration rate" (eGFR).
To read more, click here
Feature Article
Bioidentical Hormone Replacement Therapy Under Attack: An Update
Jeff Morris
As we reported in February, the ability of pharmacies to compound bioidentical hormones is at risk as a result of a “citizen petition” filed with the FDA last October by Premarin and Prempro manufacturer Wyeth (Madison, NJ). At that time we noted that there was a grassroots effort to mount opposition to the Wyeth petition, and that the International Academy of Compounding Pharmacists (IACP) had made informational resources available on its Web site.
The FDA initially set an April 4 deadline for public comment on the petition, and we expected that we would now be able to tell you about the outcome of the process. That, as it turns out, is not the case. In an interim response sent to Wyeth’s attorneys on March 31, FDA Associate Director for Policy Susan Axelrod wrote, “I am writing to inform you that the Food and Drug Administration…has not yet resolved the issues raised in your citizen petition submitted on October 6, 2005, on behalf of Wyeth. Your petition requests that the Agency take various actions with respect to bio-identical hormone replacement therapy drugs that are available from compounding pharmacies. FDA has been unable to reach a decision on your petition because it raises complex issues requiring extensive review and analysis by Agency officials…We will respond to your petition as soon as we have reached a decision on your request.”
One reason for the delay may be the sheer volume of comments that were—and are still being—received. According to Susan Cruzan, Acting Director of the FDA’s Media Relations Staff, that number was 27,000 “very brief comments” about which she could not provide any breakdown. However, an IACP spokesman said that was the number the FDA had received prior to the original April 4 deadline; he speculated that the FDA simply does not have the manpower to handle the backlog of comments. The comment deadline has now been extended until at least May 6, and we were told by the FDA’s Division of Dockets Management that as of April 18, some 38,700+ comments have been received regarding the Wyeth petition (docket number 2005P-0411). As for when the FDA might act on the matter, Cruzan said, “We do not have a specific time frame, but will address all the issues in the petition, and from the comments to dockets before responding.” Attempts to get any further information from the FDA—including how much weight was given to public comment, and whether the number of comments was higher than usual—were met with more variations on “no comment.”
Although the FDA could not provide a breakdown of comments, a perusal of those that have made it onto the agency’s Web site shows a decided slant against the Wyeth petition. One woman wrote, “My family of seven, plus extended family, including my sisters, have been successfully managed on bio-identical hormone therapy for ten years! Our health and well being depend on being able to have our physician continue treatment with BHRT… I believe the Wyeth Petition is in opposition to the best health care options for my family of seven citizens, plus my sisters. Please consider that this letter represents my entire family.” But comment is not limited to individuals. A letter from the National Community Pharmacists Association (NCPA) states, “Due to the results of [the WHI Prempro] study, and the results of the WHI estrogen alone substudy2 released March 2004, the treatment of symptomatic menopausal women with Hormone Replacement Therapy (HRT) changed significantly.
"The most recent FDA Menopause and Hormones Fact Sheet (July 2005) recommends that menopausal hormone therapy should be used at the lowest doses for the shortest duration to reach treatment goals. In many cases, women are offered a standard brand, one-size-fits-all therapy when they seek relief for the physical symptoms associated with hormonal changes. In response to a physician's prescription, compounding pharmacists prepare BHRT prescriptions that have been customized for individual patients needs, therefore ensuring, as the FDA recommends, that the patient receive the lowest possible dose of menopausal hormone therapy .
NCPA would like to reiterate that pharmacist compounding, an integral part of the practice of pharmacy, occurs in response to a licensed physician's prescription order for a specific compounded medication. Millions of Americans have unique health needs that off-the-shelf, prescription medicines, cannot meet and they rely on the customized medicines - prescribed or ordered by their licensed physicians and mixed safely by trained, licensed pharmacists -- to treat their unique conditions . It is important that the scope of the practice of pharmacy is not redefined to eliminate compounding, and that pharmacist compounding continue to be recognized as a right of the physician-patient-pharmacist relationship so that patients can continue to receive appropriate medication treatment."
Wyeth has not sat still while waiting for the FDA to rule on its petition. On February 13, it trumpeted data published in the Archives of Internal Medicine showing that in the estrogen-alone arm of the WHI study, conjugated estrogens 0.625 mg therapy did not increase the risk of coronary heart disease (CHD) in women aged 50 to 79 after an average of 7.1 years. Study investigators also concluded that there was a suggestion of lower coronary heart disease risk with conjugated estrogens among women 50 to 59 years of age. These data are particularly interesting, said Wyeth, because this younger age group most closely resembles the typical patient treated with hormone therapy. Wyeth also sponsored an April 7 teleconference to discuss an April 12 Journal of the American Medical Association report that estrogen therapy does not cause breast cancer. (See separate story in this issue’s Industry News section.)
The topic of the Wyeth petition has also begun generating considerable interest in mainstream media. An April 5 ABC News online story focused on several women who sung the praises of the BHRT treatment they had received, and were fearful of losing that right if the Wyeth petition succeeds. The article noted that while the FDA regulates manufacturing, not compounding, the Wyeth petition alleges that the growing market for BHRT drugs had led compounding pharmacies to veer toward wholesale manufacturing, and therefore should be regulated as such. Marla Ahlgrimm, founder and CEO of Women’s Health America (one of the BHRT providers named in the petition) is quoted as saying the potential side effects of Wyeth’s drugs has caused the popularity of BHRT drugs to surge, taking a significant bite out of Wyeth’s market dominance: "They really have cut into their sales, so they have to do something." But Wyeth spokeswoman Candace Steele insisted the motivation for the company’s petition was not profits, but women’s health. "The heart of this is that women are not receiving the appropriate information," she said, referring to the petition’s claim that there had been too little research and alleging that BHRT drugs were not accompanied by appropriate warning labels. "We're not at all interfering or asking that the agency interfere with medical practice or legitimate compounding." Steele reiterated this position when we spoke with her.
But IACP states that the implications of Wyeth’s proposal are far-reaching and would potentially restrict patients’ access, not only to compounded hormones, but compounded medicines overall. The organization’s executive director, L.D. King, said that Wyeth’s aims are clear: “To restrict the ability of physicians to prescribe and patients to use customized BHRT following studies that have raised serious health concerns with the company's [Wyeth's] own products." King said Wyeth's petition, if successful, would represent "a devastating blow to the access [to BHRT] women need" because of the FDA's lengthy approval process for new drugs, estimating that 38 million prescriptions would be in jeopardy.
The ABC News story mirrored one that appeared March 18 in the Des Moines Register, which gave similar testimonials from women successfully treated with BHRT drugs and fearful of the consequences of Wyeth’s petition. It quoted Dr. Jean Lorentzen of Boone, IA, who has been prescribing bioidentical hormones since 1996, as saying some of Wyeth's concerns may be legitimate—including a failure to include information on the risks of taking estrogen—but that as far as she knows, Iowa compounders provide that information to patients. "I'm just very concerned about further restricting physicians' rights to prescribe an individualized therapy for a patient for any reason," said Dr. Lorentzen. "I don't think a third party should second-guess what a physician agrees to prescribe and what a patient agrees to take.”
There has thus far been a distinct lack of interest in this topic from elected officials—or at least, an unwillingness to take sides. We attempted to ascertain the views of Sen. Michael Enzi (R-WY), chairman of the Senate Committee on Health, along with Sen. Edward Kennedy (D-MA), ranking member of the committee, and Rep. Nancy Johnson (R-CT), chair of the House Subcommittee on Health. Despite repeated attempts to elicit responses, none were forthcoming. Sen. Enzi was out of the country, and according to his press secretary, there was no previously prepared statement that could be released regarding the Senator’s position. Multiple phone and e-mail messages left with Rep. Johnson’s press secretary—who was always said to be “unavailable”—went unanswered. Those we spoke to in Sen. Kennedy’s office professed unfamiliarity with the topic of BHRT or the Wyeth petition, and a promised response never came. Part of Sen. Kennedy’s reluctance to comment may be due to the fact he has been targeted by Steven F. Hotze, M.D., director of Project: FANS, which calls itself “a grassroots effort to protect Americans' access to safe, natural medical solutions.” On several Web sites, Dr. Hotze is quoted as saying, “We know that congressional staff members have been working on legislation that could essentially create an unethical, illegal monopoly in the hormone replacement market," and contending that “Sen. Kennedy's office is currently drafting legislation that would federally overregulate the compounding pharmacy industry to the point that it would unduly burden and interfere with the doctor-patient relationship of those using bio-identical hormones.” Dr. Hotze continued, "For decades, Sen. Kennedy has proudly proclaimed he is a champion of women's health issues, but pushing a bill like this is not only bad medicine, but an insult to the American women he claims to support." However, we should note that we were unable to uncover any evidence that Sen. Kennedy actually advocates the legislation it is alleged his office is drafting. Further, according to a Supreme Court brief (No. 01-344) made by the Department of Health and Human Services, statements entered into the Congressional Record by Sen. Kennedy in 1997 were designed to "ensure continued availability of compounded drug products as a component of individualized therapy, while limiting the scope of compounding so as to prevent manufacturing under the guise of compounding." This may be the source of some of these allegations.
As for the more than 38,000 comments received by the FDA, IACP’s King called the response to Wyeth’s petition “unprecedented and very telling. On the one hand, Wyeth and a small number of paid allies support restricting patients’ access to bioidentical hormones. On the other hand, you have literally thousands of patients who are justifiably scared that Wyeth’s campaign will rob them of hormone treatments on which they and their physicians rely to treat pain and discomfort. This imbalance should make it easy for FDA to deny Wyeth’s petition.” At the very least, it’s made it impossible for the FDA to rule on the petition by the originally designated time.
Further information on the Wyeth petition continues to be available from the IACP at www.savemymedicine.org.
Feature Article
First line comprehensive care (FLCC) of chronic autoimmune diseases:
Integrative approach to causes rather than symptomatic consequences.
Russell Jaffe, M.D., Ph.D.
Part 2 of 2 (continued from last month)
To view the archive of part one of this article, click here.
Functional, comprehensive, autologous, ex vivo immune system measurements
Only a functional lymphocyte cell response assay (in contrast to a chemical detection of the presence or absence of an antibody without knowing its physiologic beneficial or harmful function) that is comprehensive (in measuring all delayed allergy mechanisms) can give us information on all these sources of immune reactions.
This will be explored in more detail later in this article, particularly given the increasing:
It is not surprising that we have what has been described as an ‘epidemic of epidemics of autoimmune and immune dysfunction syndromes’ that form the bulk of chronic ill health in our society (129-131).
Chronic or excessive exposure to reactive substances can overwhelm our adaptive mechanisms for immune defense and repair that results in further immune dysregulation and dysfunction (132,133) and in further depletion of protective reserves and resilience factors (134,135).
Clinically, this depletion of reserves and essential protective nutritives can contribute to:
Thus, identification of the body’s shift from healthy, non-reactive tolerance to delayed allergic (hypersensitivity, DTH) responses is essential to comprehensive, integrated health care (109,109). First-line of care, actionable, clinical assessments for all people with chronic pain or autoimmune / immune dysfunction illnesses are now available (108-110).
Why is this so fundamental to comprehensive or integrative care? Immune dysfunction is central to the basic mechanisms of inflammatory (really repair deficit) pain and chronic illness. Cumulative repair deficits lead to increased tissue permeability from decreased structural repair in that tissue. This is fundamental to the causes of over 1,000 autoimmune, immune dysfunction, and inflammatory cardiovascular diseases or syndromes (143).
If we can identify the items to which an individual reacts through all of the three delayed allergy (Types II, III, and IV DTH) pathways, we have the basis for more complete, accurate, predictive assessment and an individualized treatment plan.
Of course, the person needs:
Decrease in defense burden also means identification and substitution for the ingested, inhaled, or absorbed sources of delayed allergic reactions. These sources include reactive antigens derived from what we eat, breathe, and contact as well as from antigens shed by dysbiotic organisms (108,109).
Antigen cross reactions and antigen mimics
Dysbiotic organisms, parasites, and fungi in the intestinal tract can shed antigens that are identical to host proteins or food digestive remnants. Yersinia antigens cross reactivity with thyroid tissue antigens has been suggested as a potentiating variable in thyroiditis (149). Sensitization to blood group B substance even in people who have had no prior transfusion is another example of antigenic cross reactivity (150). A variety of phage infected bacteria (like hemolytic E. Coli) and anaerobic pathogens, as well as intestinal parasites have antigens that cross react with many antigens in foods (151-154). Thus we can react to a substance we have never eaten due to cross-reactivity and antigen mimicry. By restoring healthy microflora and digestive competence, people loose their pathogen hospitality (155). This improves clinical health and reduces the workload on the immune system. More attention can be given to repair and resilience than defense and delayed hypersensitivity-linked burdens that express as the symptoms of ill health (156).
Substituting for the substances to which our immune system reacts is important for rebuilding reserves and reducing the load/distress on our immune system. This allows our physical economy to move from a state of "red alert" and hyperactivity to one of balance, regeneration, and repair. This shift is central to the restoration of health (157). This shift is the basis for a sustainable remission in autoimmune and immune dysfunction conditions as the body seeks to restore immune tolerance, homeostasis and shift back to health from a fixed state of hypersensitivity / delayed allergic reactivity (158).
Immune system healthy homeostasis
Are we able to restore tolerance, homeostasis, and sustainable good health? Based on clinical experience with symptom suppressive therapies, the maxim has become: Once reactive, always reactive. This is true as long as our therapy focuses on suppressing symptoms (159). When we comprehensively identify and substitute for the reactive items, we allow immune defense and repair systems to repair and reset themselves to homeostatic tolerance (108,109). Systematic success in community based randomized controlled trials [RCTs] in fibromyalgia with and without chronic fatigue [CFIDS] (95) as well as in type 1 and type 2 diabetes support the efficacy of this approach (64). Clinical case successes in the full range of autoimmune and immune dysfunction problems are also consistent with this hypothesis (108-110).
When we concurrently address the causes of these problems, our immune defense and repair system can reset itself to a tolerant, non-reactive state. A comprehensive approach that includes the following four elements is necessary to achieve healthy restoration of immune functions:
From Claude Bernard to Ivan Pavlov; from Hans Selye to Rene Dubos, from David Felton to Bruce McEwan this message has been well documented yet remains largely unapplied in practice. The clinical cost and human result are growingly substantial; the lag from scientific documentation to integration in practice is increasingly troublesome, particularly as scientific evidence continues to grow geometrically. This means that the doubling of scientific knowledge occurs at increasingly shorter intervals.
Clinical outcome results
Beyond statistics and predictive significance, clinical outcomes using the four integrated aspects above support the efficacy of this approach. The power of the approach in resolving the causes of autoimmune or immune dysfunction case by case; patient by patient is becoming clearer as more clinical reports and successful randomized, controlled trials are reported (3,108-110,160).
Figure 1. Immune responses: Four types and their functional measurement
Figure 2. Common clinical conditions associated with various delayed allergic mechanisms.
Meaning of positive LRA by ELISA/ACT results:
| 1. Immune recognition (161)… all of the delayed allergy pathways can be programmed into lymphocyte subsets for reaction. Only a functional LRA measures all pathways. Further, beneficial (neutralizing, blocking) IgG antibodies are not measured because they do not trigger lymphocytes to respond nor do they provoke symptoms. |
| 2. Contaminant recognition (162)… we may think we react to an item when we react to a contaminant carried along in the production or processing of that food or chemical. |
| 3. Cross reaction with identical antigen or reactive epitope (163, 164) Nature is conservative. The same biological structure (‘antigen’) may exist in different systems and will cause a common reactivity. This is why, for example, people can have a transfusion reaction when they have never received blood before and why people can ‘react’ to a food they have never ingested: |
| • Gut pathogens may contain a structure (antigen) identical to one found in a food. Improving intestinal microbial ecology with probiotics, an alkaline way diet, and substituting for foods that cause delayed allergic reactions can displace pathogens and shorten digestive transit time to a healthier 12-18 hours so pathogens are less able to proliferate and the host less hospitable to their growth and toxic product releases. |
| • Related food family antigen or reactive epitope, for example, common antigens in the nightshade family may induce reactions from a food eaten to another member of the food family that has not been eaten where some antigenic cross reactivity may occur. |
| • Individual’s tissue antigens may cross-react with a tested substance. This only occurs when repair deficits have exposed tissue antigens that are designed to be hidden. Stimulating repair can rebuild the ‘blood-tissue’ barrier to healthy, low permeability and stop this ‘auto-antigen’ exposure. |
A positive result on lymphocyte blastogenic* or mitogenic** response assays, for example, LRA by ELISA/ACT, can be due to one of three causes. These include immune recognition of a:
Procedure, method & clinical results for LRA by ELISA/ACT tests
The LRA by ELISA/ACT procedure is straightforward. It requires a 12 hour period of water only followed by a one-ounce blood draw. This is the amount of blood the bone marrow produces in about one hour.
For accurate results certain substances need to be avoided for a few days. Steroid medications need to be avoided for four (4) days (166). A ‘steroid bridge’ is available to help in this interim if needed (165). Aspirin and antihistamines also stabilize lymphocyte membranes and reduce reactivity (168,169). Aspirin and antihistamines need to be avoided for two (2) days prior to drawing the blood sample.
The whole blood sample is sent to the lab via overnight courier. No processing of specimen is required. During transport the specimen is kept cooled between 4º-10º C so the cell metabolism is reduced. After receipt, the sample is centrifuged gently. The cell-rich plasma (CRP) is aspirated and aliquoted into microtiter plates precoated with the various substances (antigens / haptens) to be tested (170).
An entire LRA assay can be performed on only 40µl of CRP. The sample is incubated at 35±2ºC for three hours. This is long enough to measure the initial response when a lymphocyte recognizes a substance it has been pre-programmed to respond to as a delayed allergen. If the cell culture were continued for several days, DNA synthesis could be monitored by radioactive thymidine incorporation. If the cell culture were continued for several weeks, colonies of proliferated cells could be observed. After this brief incubation, the cells are examined to determine if enzyme activation has occurred (171).
LRA by ELISA/ACT is unique. It is the first ELISA method to use the surface of a living cell (lymphocyte) as the source of the amplifying detection enzyme (172). Each specimen has an internal positive and negative control performed as part of routine quality control. A >50% reactivity is considered a strong reaction, while a 5-50% reactivity is considered an intermediate reaction. Both of these reactions are equally burdensome to the immune system. Under optimal conditions, strong reactions take longer to reset. Typically, six (6) months are needed to reset strong reactions while intermediate or moderate reactions can be reset in three (3) months. A <5% cell reactivity is indistinguishable from background responses and is within the usual tests range.
Validity, Reproducibility, Sensitivity, and Specificity
The classic way of determining the validity of a test is by comparing the observed measurement or results to some accepted, objective, physical "gold standard" method (174, 175). However, there is no such universally agreed upon standard for determining delayed hypersensitivity reactions (176). Therefore, validity must be established by showing that the test results are predictive of or are directly related to clinically measurable or observable phenomena (signs and symptoms). In other words, does substitution for the reactive items detected by the tests bring clinical improvement for each individual. This is the clinical “gold standard” (177).
Regarding validity based on predictive value of clinical phenomena, the LRA by ELISA/ACT was performed on 81 consecutive cases of autoimmune or immune dysfunction syndromes. Entry criteria included persisting, treatment-resistant pathology for more than five years. Diagnoses of subjects included autoimmune conditions [rheumatoid diseases, multiple sclerosis (MS), asthma, ulcerative colitis (UC), eczema, psoriasis, lupus (SLE), thyroiditis, diabetes], and immune dysfunction conditions [fibromyalgia, and chronic fatigue (CFIDS)] (178).
Each person filled out two symptom questionnaires (the Cornell Medical Index Questionnaire and a Health Appraisal Questionnaire prepared by ELISA/ACT Biotechnologies) and rated the intensity of their primary symptoms on a scale of 1-100 prior to beginning the recommended ELISA/ACT program based on their individual LRA tests results. To assess long-term outcomes, these same subjects again rated their primary symptom intensities at intervals over 6-30 months.
The results showed a primary symptom intensity of:
77.4 ± 14.5 before and
26.4 ± 18.2 after 6 to 30 months of following this healing program (p < .0001). These results are based on real world ‘best efforts’ to follow healing suggestions. This demonstrated clinical outcome successes as well as statistically significant improvement in this previously treatment-resistant group (178).
These results suggest a strong correlation between the reduction of symptom intensity and the substitution for reactive substances based on LRA by ELISA/ACT tests and compliance with the available treatment guide.
During the three year development phase of the LRA by ELISA/ACT tests, two procedures were utilized to establish reliability:
Confirmation of tests results in practice can best be achieved by demonstrating that clinical signs and symptoms remit when reactive substances are avoided. However, reactivity to a substance is not always synonymous with easily linked clinical signs and symptoms by the individual because of the delay between exposure and symptom provocation. This delay can be several hours to several weeks (180,181). This is in contrast to Type 1 (IgE) hypersensitivity reactions (not tested for with LRA assays) or a psychologically programmed (distress) response (182).
In community based randomized controlled studies of chronic, treatment-resistant fibromyalgia with or without chronic fatigue the sustained improvements suggest predictive significance for LRA by ELISA/ACT tests (64). Similar results in both type 1 and type 2 diabetics are also supportive of this comprehensive care technology breakthrough (95). Clinical reports from a database of over 40,000 cases are further reinforcement of the value and validity of this comprehensive, functional, ex vivo approach (108,109).
Clinical application and utility
Identification of LRA by ELISA/ACT reactions to over 420 substances makes this technique the most comprehensive available. Categories include foods and food additives, environmental chemicals, medications, molds, herbs, and danders. When these reactions are of a delayed nature it is often clinically challenging, even with the most careful history, to make their determination. Use of this ex vivo technique allows the body to ‘speak for itself’ under controlled laboratory conditions (108,109).
LRA by ELISA/ACT tests are useful tools for identifying the reactive substances of delayed hypersensitivity by providing a comprehensive "immunologic fingerprint" of our delayed reactive substances. When these substances are identified, best efforts made to substitute for them, and a sensible repair program engaged, the reduced immunologic distress and repair deficit pathology can often be reversed and sustainable remissions routinely occur.
Immunologic dis-repair, despair, inflammation, and tissue destruction induced by delayed hypersensitivity reactions no longer mean chronic suffering and morbidity. A more scientific era of identifying the causes of ill health and comprehensively stimulating repair can open a bright chapter in comprehensive, integrated, evidence based care and caring.
The LRA by ELISA/ACT optional lab director’s interpretive treatment guide includes:
Clinical outcomes and results:
10/91: Obtained LRA by ELISA/ACT tests results and started recommended plan.
1/92: "85% better", off cortisone; Dipentum reduced 50%
6/92: Asymptomatic for 3 months
"...last 6 months have been the best in last 10 years...
my ELISA/ACT plan made the difference"
Sustained improvement over the past decade.
Annual sigmoidoscopies documented “cobblestone granuloma” from 8-25 cm in the colon. Patient reports excellent compliance with all therapeutic interventions. Lack of response to therapy was ‘frustrating and depressing’.
In November 1990, she was clinically symptomatic with a ESR of 60. LRA by ELISA/ACT tests were performed. An unusually high number of reactive substances was noted (45 items). Substitution for reactions was associated with complete symptom remission after just one month.
Follow up LRA by ELISA/ACT in 11/91 showed a 54% decrease in reactive items (from 45 to 20). Continuing in remission, she followed the updated plan.
Further follow up LRA by ELISA/ACT in 10/92 showed a further reduction in reactions to 17 items. Subsequent tests revealed 3 reactive items out of 343 items tested. The patient remains asymptomatic at 10 years follow up.
JA went to rheumatologists, physiatrists, and osteopaths without relief. She reported transient relief from chiropractic care.
Laboratory data was unremarkable except for first morning urine pH that was consistently 5.5 suggesting cellular net acid excess (metabolic acidosis).
JA was tested for delayed allergic responses (LRA by ELISA/ACT). She showed seven reactive substances out of 343 LRA cell cultures performed. Following the treatment guide, she did her best to eat 80% alkaline forming foods (following the Alkaline Way Guide), took targeted supplements and following healing actions. After 6 months, she reported “>75% reduction in back pain, stiffness is gone, and overall health is 90% better”. Constipation resolved; she felt optimistic and more emotionally stable. First morning urine pH was consistently in the 6.5-7.5 range suggesting correction of her cellular metabolic acidosis. Her summary: “The wind is at my back rather than in my face.”
Separately, following her LRA by ELISA/ACT plan, Claire Musickant has reported her more than 10 year sustained remission from disabling fibromyalgia and chronic fatigue (CFIDS) in her book ‘Fibromyalgia, My Journey to Wellness’ (96) now in its second edition. We have published successful outcomes in a community based randomized controlled trial (RCT) based on 3-4 year outcome follow-ups (97). Recent follow up of those cases show continued improvement and sustained remissions now exceeding 10 (ten) years in over 85% of those cases.
DK presents as a 25-year-old woman with a 22 year history of treatment- resistant asthma and chronic rhinitis. By high school, she regularly used three inhalers while receiving regular immunotherapy shots and taking H1 blockers (antihistamines).
LRA by ELISA/ACT tests were performed in August 2001. Reactions were noted to 12 out of 377 substances tested. After one month, rhinitis was gone and asthma was less symptomatic. Inhaler use with exercise remained. Follow-up at six months showed her symptom free. Repeat tests found her reacting to only two of the initial items. As often happens when persisting maldigestion, dysbiosis, and intestinal wall repair deficits are present, new reactive items develop prior to full restoration of digestive and mucosal wall health. She continues to follow her plan of substitution for reactive items, an alkaline way diet, targeted supplements, and healing actions.
She continues to be in remission.
BB presented as an 11-year-old boy with unremarkable development and insulin dependent type 1 diabetes. Typical blood sugars of 350 mg/dl and glycosylated protein (Hgb A1c) of 8 mg/dl. His uncle, a chiropractic physician, recommended niacinamide and acetylcholine. This provided transient benefit. Even on human insulin (Humulin) 10 U TID his blood sugars remained in the 300 mg/dl range.
In January 2003 he was evaluated using LRA by ELISA/ACT tests. Reactions were noted to 13 of 377 items tested. Following his plan for five months, he was reported to have:
In a community based randomized, controlled trial (RCT) we noted systematic improvements in these same markers in both type 1 and type 2 diabetics (191).
EO presented as a 35-year-old mother of three with an unremarkable presentation except for 18 Kg (40 pound) excess over her lean target weight. She reports that she ‘always has to push myself to get through the day’. Observations include:
She was evaluated using LRA by ELISA/ACT tests were she was found to react to four items and 1 food group out of 343 items tested. She was started on a comprehensive program of substitution for reactive items, Alkaline Way diet, targeted supplementation, and healing actions. In addition, two grains of desiccated thyroid daily were initiated.
Follow up at six months found her ‘more energetic and pleased with my nails and hair’. She had lost 10 Kg (22 pounds) ‘without dieting’. Lab test results included:
| Lab Test | Initial values |
Results Before LRA |
Improvement After LRA |
| a. Free T3 | 120 | 430 | 380 pg/dl |
| b. Free T4 | 0.5 | 0.9 | 1.1 ng/dl |
| c. TSH | 12 | 5.2 | 4.4 IU |
| d. Microsomal Ab | 2048 | 8:1 | Not detected |
| e. Anti-thyroid Ab | 4096 | 8:1 | Not detected |
| f. Cholesterol | 325 | 220 | 190 mg/dl |
| g. Triglycerides | 280 | 150 | 145 mg/dl |
| h. 2º PP Glucose | 186 | 108 | 94 mg/dl |
| i. 2º PP insulin | 80 | 160 IU | 150 IU |
Further follow up at one year included repeat of LRA by ELISA/ACT tests. She was found reactive to only two of 343 items tested. She had now lost 18 Kg (40 pounds) and was at her lean body weight while not restricting calories. Basal morning temperatures were increased and now within the healthy range. Data observed after the LRA interpretation plan are shown above on the right.
These cases illustrate the applicability of this fundamental approach to the first line comprehensive care management of autoimmune, immune dysfunction, and chronic inflammatory / repair dysfunction syndromes.
Conclusions: Examples of integrative care philosophy and practice have been reviewed. The benefits of functional, comprehensive ex vivo tests in redressing the causes rather than responding to the symptoms proves well accepted by practitioners and patients alike. The economics of care are favorable. LRA by ELISA/ACT tests and clinical outcome plans have been used for over 20 years. Through a variety of clinical outcome studies and case examples, this ‘gold standard’ of integrative care is now usual and customary, medically necessary and appropriate for the management of autoimmune, immune dysfunction, and chronic inflammatory conditions.
Additional conclusions about first line comprehensive care approach are:
May all be well and joyful.
Russell Jaffe, M.D., Ph.D.,, CCN, NACB, FRSM, FASCP, FACN, FACAAI, FALMI is Senior Fellow of the Health Studies Collegium research foundation. He is developer of various functional methods from occult blood detection in early colon cancer screening to platelet dose-response aggregation studies in coagulation to the LRA by ELISA/ACT tests and plans, the d-penicillamine nutritional and toxic mineral assessment protocol, the ascorbate calibration protocol, magnesium uptake protocol, glutamine recycling protocol, among others. He serves as director of: ELISA/ACT Biotechnologies, LLC and, PERQUE, LLC nutritive supplements.
He is recipient of the International Scientist of the Year 2003 awarded by the International Biographical Commission of Cambridge, England to recognize his lifetime contributions to Biochemistry, Clinical Medicine, and Immunomics. He was recently elected as a Fellow of the National Academy of Clinical Biochemistry. He also maintains Fellow status in the American Society for Clinical Pathology, American College of Nutrition, American College for Allergy, Asthma, and Immunology, American Medical Laboratory Immunology, and the Federation of Clinical Immunology Societies. He is also a certified clinical nutritionist (CCN).
For information about the American Society of Integrative Medical Practice standards, membership information or for questions about Certification Training in Integrative Medicine, see resources below.
Resources guide:
Feature Article
Cellular Aging Clocks: Reversing Time’s Arrow With Tetrahedral Spin Chemistry
Todd Ovokaitys, M.D.
Transcending the biological aging process – slowing, stopping, and even reversing it – is likely to be found at the level of DNA chemistry. Recent research suggests that all the proposed mechanisms of aging have as a final common pathway discreet structural changes in DNA. The ability to intervene in these changes and recreate the structures of earlier physiologic age is now an achievable feat that may mark the birth of increasingly powerful rejuvenation technologies.
We will review the basics of DNA chemistry and the ways DNA marks the passage of time. In understanding these mechanisms we will see how tetrahedral forms are intimate to these timing events and their potential reversal. Once these processes are defined, we will reveal the breakthrough discovery of high spin tetrahedral chemistry and suggest its implications for sustained anti-aging.
For the first time in scientific history, a randomized double blind placebo controlled clinical study has established the dose response to high spin tetrahedral chemistry. The results indicate a dramatic reduction of physiologic aging chemistry. In addition, several measures of well being showed highly statistically significant improvement in the active treatment group.
Basic DNA Chemistry: DNA, or deoxyribonucleic acid, is the master molecule of cellular information. From a single fertilized cell, the DNA of the firstmost nucleus has all the information required to generate all the specialized tissues and functions of 100 trillion cells in the adult human.
DNA has two fundamental components – backbone structure and base pairs. In this organization, DNA can be likened to a spiral staircase – the outer spirals form the structural backbone and the stairs are the function rich base pairs. The backbone is formed by alternating and connected molecules of phosphate and the 5-carbon sugar deoxyribose.
Two strands of backbone sugar-phosphate wrap around each other in an elegant spiral referred to as a double helix. One complete spiral is made for every 10 base pairs that line the central core, a pitch of 36 degrees per base pair. The spirals are anti-parallel, meaning that the polarity of direction of reading the base pairs is opposite from strand to strand.
In the central axis the base pairs line up perpendicular to the axis of the spiral backbone. There are four DNA bases – the purines adenine and guanine, and the pyrimidines thymine and cytosine. The two bases of a pair align in complementary fashion – adenine with thymine, guanine with cytosine. This complementarity creates hydrogen-bonding forces that snap the base pairs together with greater accuracy than any mechanical zipper. The complementary form also permits each strand to be the template for replicating the other strand with exquisite precision. The fundamental effector of DNA information is the triplet code. Each sequence of three bases codes for the placement of a specific amino acid in an enzyme or structural protein chain. The enzymes thus formed catalyze all of the complex reactions of living cells, while proteins provide form and structure, such as collagen in hair, skin, and nails.
As elegant the process of translating the triplet code of a gene into a completed protein, even more sophisticated is how a cell knows which of its 100,000 genes to transcribe, how many copies, and in what timing and sequence. The 3 billion base pairs of DNA information organize the outplay of coding uniquely in each of the hundreds of different types of cells in the human body. Although many mechanisms of gene regulation are being defined, perhaps the most important single organizing principle is achieved through tetrahedral form chemistry.
A tetrahedron is a four sided pyramidal form with equilateral triangular faces. The name of the simplest organic chemical group with this shape is a methyl group. A methyl group has a carbon atom in the center, a hydrogen atom at three points of a tetrahedron, and a fourth point free for the attachment of another atom or molecular group.
Methyl groups modify a specific DNA base at birth to create a fifth element of DNA – cytosine bases with a methyl group bonded to the number 5 position in the cytosine ring. This modified DNA base is called 5-methyl-cytosine. The level of cytosine methylation at birth is quite significant, and varies from 2 – 6%, depending on the type of cell.
The placement of methyl groups on cytosine bases is highly information enriched and creates a fingerprint that differentiates each type of cell. The presence of a methyl group tells the cell which parts of the DNA code not to transcribe for that kind of cell. These tetrahedral anchor points thus tell a muscle cell not to transcribe brain proteins, and so forth, for all cell types and functions throughout the body.
In addition, methyl groups prevent the activation of genes that could accelerate aging or induce aberrant cell growth. The placement and presence of these groups is intimate and vital to maintaining the healthy organized function of cells and tissues. The dynamics of tetrahedral methyl groups may prove to be at the core of regulating the potential for longevity.
DNA Timing Mechanisms: Recent research suggests that the final common pathway of aging is the gradual loss of methyl groups from DNA. Current proposed mechanisms of aging, such as oxidant stress, environmental toxins, vitamin and nutrient deficiencies, and activation of deleterious genes all appear to accelerate methyl group loss.
Different levels of reduced DNA methylation are associated with the risk of specific health problems. A 20% loss of cytosine methylation increases the risk of certain tumors, particularly of the linings of the digestive and reproductive tracts. This represents a loss of information organization both of replication of the tissues and of ideal immune surveillance.
An approximately 40% loss of methyl groups from birth levels, for humans and other mammalian species, is usually associated with degenerative demise of the organism. Displacement of methyl groups interferes with regulating DNA functions and preserving the integrity of cells and tissues. Slowing, stopping, and reversing the loss of methyl groups from DNA is a process of slowing and even reversing aging at the level of DNA itself.
A related DNA timing mechanism is the length of the telomeres. Telos is the Greek word for ‘end’ so the telomeres are the ends of the chromosomes. When cells divide, the initially long sequence of telomere codons tends to chip off to a shorter length. Telomeres are likened to the protective coatings at the ends of shoestrings that prevent them from fraying. When telomere length reduces to a critical level, cells tend to lose their ability to replicate further.
The blood chemistry marker for impaired DNA methylation is elevation of homocysteine. High homocysteine levels also accelerate shortening of the telomeres. Supporting and supplementing the same chemistry that lowers homocysteine has the dual rejuvenation benefit of preserving and even boosting DNA methylation and sustaining the length of the telomeres.
Homocysteine the Overall Functional Barometer: The level of homocysteine in the blood gives a general reading of the condition of methyl group transfer chemistry in the body. The higher the homocysteine level above 6.3, the poorer the DNA methylation and the greater the associated health risks.
Homocysteine is a metabolic breakdown product of the essential amino acid methionine. It is necessary to have some homocysteine in the blood for its role in vital metabolic cycles, but beyond a relatively low threshold it becomes increasingly toxic.
Homocysteine above low levels combines with LDL cholesterol to promote oxidation. Unoxidized cholesterol even at high levels appears to be harmless to blood vessels. However, even a small amount of oxidation renders it an agent of inducing atherosclerotic changes.
Elevated homocysteine also increases the tendency of blood to clot to precipitate acute vascular thromboses, as in heart attacks and strokes. In addition, high homocysteine accelerates telomere shortening of vascular lining cells and impairs endothelial nitric oxide production, predisposing to blood vessel spasm.
Based on all these factors, cardiovascular risks rise exponentially above a homocysteine level of 6.3, as the following chart from a large population study shows:
| Homocysteine Level | <6.3 | 6.3 | 10 | 15 | 20 |
| Relative Cardiac Risk | <1 | 1 | 2 | 4 | 9 |
Thus at a level of 15, the risk of a major cardiac event is 4 times that of the general population. Also a recent study from Boston University indicates that a level over 14 carries double the risk of Alzheimer’s disease. Noteworthy is that many labs call a level of up to 15 normal, resulting in what is likely widespread undertreatment of elevated levels.
In addition, homocysteine accumulates in malignant cells, altering the structure of proteins and DNA. Elevated homocysteine may thus directly increase the risk of tumor formation. Encouraging vigorous intervention, studies that have aggressively lowered homocysteine have reversed premalignant cells to normal cells and have even reversed the blood vessel narrowing of atherosclerosis.
There are three principal pathways through which the body detoxifies homocysteine. The first of these pathways uses vitamin B6 (pyridoxine) and zinc to convert homocysteine to the beneficial sulfur amino acid cysteine. The cysteine thus formed may then be used to synthesize glutathione, one of the most powerful antiaging antitumor antioxidants ever studied.
The second pathway requires folic acid and vitamin B12 and converts homocysteine to the beneficial and lipotropic amino acid methionine. Deficiencies of B12 and folic acid are well known to cause anemia, neurologic, and psychiatric problems, preventable and even reversible with supplementation.
The third and most potent pathway uses a nutrient known as trimethylglycine, or TMG. Also called betaine because it is derived naturally from beets, it has a rich supply of three methyl groups to donate. Through a specific enzyme present primarily in the liver (betaine-homocysteine methyltransferase), TMG donates a methyl group to homocysteine that drives the production of methionine followed by the generation of SAMe, or S-adenosyl-methionine.
The most versatile and important methyl group donor in the body, SAMe, is formed when methionine combines with the energy molecule ATP (adenosine triphosphate). Of the few hundred known methyl group transfer reactions in the body, SAMe is the methyl group donor in about half of them. Most significantly, all of the enzymes that restore methyl groups to DNA use SAMe as the exclusive methyl group donor.
Spinning Tetrahedrons – Root Currency of Organic Chemistry: Methyl groups are used for far more than key anchors on DNA. The single carbon transfer in the form of a methyl group is the basic currency of all organic chemistry.
Methyl groups are used to make serotonin, melatonin, and other neurotransmitters. Methyl group donors support the myelination of nerves and the rebuilding of joint tissues. Numerous proteins, enzymes, and membrane lipids require methylation for optimum function. There is even an enzyme (protein isoaspartyl methyltransferase) that uses methyl group donors to rejuvenate faltering enzymes and proteins to a functional state again.
Studies using SAMe directly have shown antidepressant effects as potent as antidepressant drugs that work in a quarter of the time without side effects. Other studies have shown marked relief of joint pain in arthritis, and the repair of liver tissue even with cirrhosis.
The main drawback of using SAMe directly is cost – the suggested therapeutic doses of 800-1600mg per day typically cost $5-$10 per day. The second potential drawback is possible homocysteine elevation. Once SAMe donates its methyl group, it becomes homocysteine.
The Potent TMG: A safer and more cost effective method of boosting SAMe is providing TMG, which also lowers homocysteine levels. In a study conducted in the early 1950’s persons who had just had a heart attack received either high dose TMG, 9 grams per day, or placebo. After one year, mortality was 25% in the placebo group, whereas the treatment group had no mortality whatsoever.
Animals fed TMG have reduced body fat and increased muscle. Supplemental TMG may increase liver SAMe levels up to fourfold and protect the liver from the harmful effects of alcohol and other hepatic toxins. TMG has also been shown to enhance athletic performance and increase endurance.
The most drastic defect of methyl group chemistry is a hereditary condition known as homocystinuria. The enzyme defects in this condition may raise homocysteine levels into the 100’s. In the most severe forms even young children may develop severe vascular and neurologic disease. Although vitamins B6, B12, and folic acid may reduce homocysteine to some degree (and possibly raise SAMe), they tend to do little for clinical symptoms in this condition. In contrast, high dose TMG has not only further lowered homocysteine; in many cases it has reversed vascular and neurologic symptoms and premature aging. The only way that women with homocystinuria have conceived and had normal deliveries has been with vitamins supplemented with high levels of TMG.
Pulse Wave Resonant Laser Technology for Accelerated Tetrahedral Spin: Through a patented technology used at Gematria Products, pulsed laser waves have been used to resonate TMG methyl groups to a high spin energy state. This phenomenon has been measured with X-ray crystallography, a procedure that locates atoms within a crystal lattice to a high degree of precision. The crystallography readings show a significant increase in the bond angles of TMG methyl groups consistent with a marked increase in spin rate and increased free energy of the methyl group bonds.
The enhanced free energy is likely to accelerate enzymatic processes of methyl group transfers. This may facilitate DNA remethylation and even generate higher vibrational DNA.
In a pilot test of activated TMG, one gram of activated TMG plus cofactors (3 capsules) was compared to 800mg of SAMe (4 capsules of 200mg each) for the ability to raise SAMe levels. Taking SAMe resulted in a low normal level of 4.9, whereas taking activated TMG gave a much higher level of 6.2 at less that one fifth the price.
First Ever Dose Response Study: We have just completed the initial phase of data analysis of the first ever dose response study of the effects of activated TMG. A formal double blind randomized prospective placebo controlled clinical study, the first phase of the study focused on the HeartGems formula with activated TMG and cofactors and its effects on blood chemistry and clinical symptoms. The dramatically positive results and their implications are as follows:
Statistical analysis was done on the results to derive scientific p values. A p value is the probability that a result will occur by chance alone. For example, the p value for tossing a tail in a coin flip is .5 or 50%. Values below .05 or 5% are felt to be statistically significant - the lower the value, the greater the significance of the results. A value of .001 is felt to be highly significant, and anything at or below .0001 is very highly significant for the difference between the treatment and control groups. Homocysteine results for the treatment group at baseline, 1, 2, and 3 months were as follows:
| Baseline | 1 month | 2 months | 3 months | |
| Homocysteine | 9.2 | 7.1 | 6.8 | 6.1 |
| P value | .00001 | .00001 | .00001 |
For the placebo control group the values were as follows:
| Baseline | 1 month | 2 months | 3 months | |
| Homocysteine | 7.8 | 7.3 | 7.9 | 7.9 |
| P value | ns | ns | ns |
Even more dramatic is the reduction in homocysteine for the treatment group subjects that started with high homocysteine levels at or above 10.
| Baseline | 1 month | 2 months | 3 months | |
| Homocysteine | 13.2 | 9.3 | 8.3 | 7.3 |
| P value | .009 | .001 | .00001 |
This drop in homocysteine level is comparable to the chemistry of persons in their 60’s becoming that of persons in their 20’s or 30’s.
As each one-point drop in homocysteine may reduce cardiac risks 10-12%, this suggests an up to 60-70% risk reduction for this group.
Subjects also took intensive symptom surveys that compared them to the general population. The scores are in percentile rank, the higher the percentile the greater the symptoms. A person at the 60th percentile has more symptoms of that type than 60% of the general population.
For the anxiety scale, persons in the treatment group had the following results:
| Baseline | 1 month | 2 months | 3 months | |
| Percentile | 56 | 40 | 27 | 24 |
| P value | .05 | .0001 | .0001 |
This indicates a very highly significant reduction in anxiety scale for the treatment group. There was no significant reduction in the placebo group.
Further analysis also indicates significant reductions in depression, obsessive compulsive, paranoid, hostility and global symptom scales in the active treatment group.
Blood samples have also been collected for the direct measurement of the dose response of SAMe and DNA methylation levels. This is the first such dose response study in scientific history and may give us a specific measure of the antiaging effect achieved directly at the DNA level.
As the data analysis continues we will strive to share more information as appropriate.
Based on these results, it can be strongly recommended to take 3-6 HeartGems daily for antiaging effects at the DNA level and for general health and well being. Persons with known elevated homocysteine levels may require higher intake amounts for optimum results, best assessed with widely available blood testing.
If you are interested in more information, you may go to our Web site at www.gematria.com or call us at 760-931-8563. You may also e-mail us at info@gematria.com.
Todd Ovokaitys, M.D. was formally educated at Northwestern University, where he was 1st in his class of 1800 with a 4.0 GPA. From Northwestern, he was accepted into a combined, accelerated undergraduate/medical school program at the highly esteemed Johns Hopkins University. Following this training he completed an Internship, Residency, and Chief Medical Residency in the Georgetown University Hospital System. This was followed by a two year Fellowship in Pulmonary and Intensive Care Medicine, also at Georgetown University Hospital. At Georgetown, "Dr. Todd" participated in formal studies of T cell immune function after harvesting lymphocytes from the lung via fiber optic bronchoscopy. In addition, this training involved intensive care of many persons afflicted with HIV infection, as the lung is a common target following the immunologic breakdown of this condition. Aware of the extreme limitations of treating HIV through ordinary conventional means, Dr. Todd began a search for less intrusive solutions. The concept of using the subtle differences of genetic organization between the viral and human genomes was the launch point for exploring new avenues of molecular resonance technologies. In concept, the slight differences of resonance signatures between the viral and human genomes could be used to selectively target and eliminate infected parts of cells leaving uninfected normal cells unharmed. After studying the background work on the effects of electromagnetic radiation on living systems, Dr. Todd commissioned a colleague with the expertise to design and build a fundamentally new laser electromagnetic resonance technology. This new laser optical technology has been patented worldwide as WO97/22022 and as U.S. #6,064,500, with U.S. patent 6,811,564,B1 and worldwide patent WO02/02187, Administration Systems for Dietary Amino Acids, Nucleotides, and Other Bioactive Substances, pending.
Feature Article
Talking to Your Patients & Colleagues about DHEA
Alan P. Mintz, M.D.
Dehydroepiandrosterone (DHEA) is a member of the steroid hormone family that is produced by the zona reticularis of the adrenal cortex in response to pituitary ACTH stimulatory signaling. It is the hormone that is present in the greatest abundance in circulation. DHEA levels peak at around age twenty, and then decline by approximately ten percent per year, with great individual to individual variability. By age 70, DHEA levels reach a relatively stable trough level of 10-20 percent of its young adult levels.
DHEA was first isolated in 1931, by Dr. Adolf Buternandt, whose data were published in 1934. (Butenandt A. et Dannenbaum H., 1934. Z physiol, Vol. 229, 192.) The publication of the structure of DHEA preceded that of testosterone by one year.
In the 1950’s, DHEA was isolated from human serum, and in the latter part of that decade, the first reports of DHEA demonstrating a decline in level with aging were reported. This was noted for both males and females.
In the 1960’s, DHEA was found to be an intermediate molecule in the testosterone synthesis pathway, and this data was the basis for the initial embrace of DHEA supplementation as a potential body building/performance enhancing aid. The utility of DHEA in this regard was generally unspectacular. High dose DHEA supplementation favored conversion to estradiol in addition to any small benefit in terms of testosterogenic effect, which limited its value as an androgenic supplement, and it’s use as a high dose supplement was short lived. By the 1980’s, DHEA was universally stocked in nutrition and health stores at lower doses and marketed as a more general aid to good health and function with aging.
DHEA followed a checkered path in the subsequent decade. In 1986 the FDA reclassified DHEA as a controlled drug based on the lack of well delineated dosing data and a paucity of literature regarding the risks of long-term supplementation; but in 1994, the U.S. Dietary Supplement Health and Education Act re-reclassified DHEA (this time based on the lack of data demonstrating long term supplement risk) as a food supplement, once again allowing it to be sold over the counter, where it has remained since.
When looking at DHEA as a weapon in the medical armamentarium, it is not typically mentioned in the same tones and with the same volume as testosterone, growth hormone, thyroid hormones, or estradiol and progesterone, but like a good character actor, it still plays a role in a balanced approach to the consideration of the utility of hormone supplementation. DHEA would be the Harvey Keitel of hormones, to Testosterone’s John Travolta, or Joan Cusack to estradiol’s Meryl Streep – important in the big picture, integral to the fabric of the film, but not the star.
No matter the subject of a hormone discussion, the standard caveat applies. We should require more than mere association between the presence or absence of a hormone and an associated finding; we should also require data that demonstrates the effect of altering that state. Whenever possible, Cenegenics strives to follow literature that is not only based on the association of low or high hormone levels and disease risk, but also examines outcomes associated with directed intervention. Only meteorologists and economists get the luxury of only telling people what has happened, we want data that give us an idea of what our interventions will do in the future.
So, today we will endeavor to put the use of DHEA in a rational clinical context. As with testosterone in last month’s conference, today we will focus on the literature of DHEA and its replacement data in a system-by-system review.
Quick note regarding DHEA levels
DHEA, like cortisol, follows a diurnal secretion/level pattern. This makes sense, given DHEA’s secretion is, like that of cortisol, stimulated by pituitary derived ACTH. Unlike cortisol, DHEA secretion is prolonged rather than pulsatile, and DHEA has a longer serum half-life (10-20 hours), making for a much less exaggerated daily peak and trough levels. This also makes for readily valid measurement that is not as time dependent as it is for cortisol.
General
A good starting point in the DHEA literature is a study published in the Proceedings of the National Academy of Science in 1996, by Claudine Berr. This study followed 622 adults, with an average age of 74 upon study entry. The study population was followed for DHEA levels and total mortality risk, functional status, psychological state, and mental status over the proceeding 4 years. In women, DHEA levels were directly related to scores of well-being, cognitive function, and functional status. In men, DHEA levels were inversely related to total mortality risk. Neither group demonstrated a specific Alzheimer’s Disease (AD) risk based on DHEA levels, and the mortality data for women at the end of 4 years was not significant.
http://www.pnas.org/cgi/content/full/93/23/13410
Barrett-Connor, in the New England Journal of Medicine, 1996, published a prospective study of baseline dehydroepiandrosterone sulfate levels and associated risk for mortality and cardiovascular disease in 242 men, aged 50-79, who were followed over a 12 year period. In men with no history of heart disease at base line, the age-adjusted relative risk associated with a DHEAS level below 140 micrograms per deciliter was 3.3 (P less than 0.05) for death from cardiovascular disease, and 3.2 (P less than 0.05) for death from ischemic heart disease. In multivariate analyses, an increase in DHEAS level of 100 micrograms per deciliter was associated with a 36 percent reduction in mortality from any causes (P less than 0.05) and a 48 percent reduction in mortality from cardiovascular disease (P less than 0.05), after adjustment for age, systolic blood pressure, serum cholesterol level, obesity, fasting plasma glucose level, cigarette smoking status, and personal history of heart disease. Of greatest interest here is that baseline determination of DHEA levels was associated with long-term health risk, even in subjects with no diagnostic history of previous pathology.
DHEA and Heart Disease
The relationship between low DHEA levels and risk for heart disease have been shown in several studies.
The Massachusetts Male Aging Study (MMAS) included DHEA as part of their thorough prospective evaluation of heart disease mortality. The MMAS followed a random sample of 1,709 men aged 40-70 years at baseline over a nine-year period. Men in the lowest baseline quartile for DHEA levels had a relative CAD risk of 1.6 compared to those in the other three quartiles. This risk was independent of confounding risk factors including age, obesity, diabetes, hypertension, smoking, serum lipids, alcohol intake, and physical activity.
Muller, in the Journal of Clinical Endocrinology and Metabolism (JCEM), 2003, performed a meta-analysis of the androgen/CAD literature; pointing out that 21 of 33 cited studies associated low DHEA levels with increased CAD risk. Eleven of the studies were neutral, and one study associated higher values of DHEA levels with higher CAD risk. Muller’s conclusion was that higher levels of DHEA are associated with a mild reduction in CAD risk.
http://jcem.endojournals.org/cgi/content/full/88/11/5076
A few interesting side notes regarding DHEA and the heart
Osorio, in Hormone Research, 2002, reported that DHEA levels fell after acute myocardial infarction. The study broadly concluded that drops in DHEA level were an epiphenomenon of CAD rather than playing any risk related role, and only followed subjects nine days post-MI, but it does raise the intriguing point that cardiac tissue may interact with as yet to be elucidated hormone synthesis/inhibition pathways.
Nakamura, in Circulation, 2003, demonstrated localized production of DHEA by cardiac tissue, and showed a decline in DHEA production in association with a rise in aldosterone production in the failing heart. His hypothesis is that DHEA exerts a cardioprotective effect and is associated with more favorable non-androgenic hormone levels in healthy hearts. Whether or not this is accurate, its association between hormones and their effects on each other is intriguing.
http://circ.ahajournals.org/cgi/content/abstract/110/13/1787
In a study published in the JCEM this month, Muller reports the results of a 400 subject study demonstrating that a 1 SD above the mean DHEA level was associated with a 0.76 relative risk for the presence of metabolic syndrome, an important CAD risk marker.
http://jcem.endojournals.org/cgi/rapidpdf/jc.2004-1158v1
DHEA and its Effect on Mood and Well-Being
For decades, DHEA has been touted as a useful intervention for treating depression or improving mood. In the study previously mentioned by Berr, women whose DHEA levels were better maintained scored higher on measures of mood. This correlation has been shown in several articles:
Cawood, in 1996, evaluated mood in relation to ovarian and adrenal steroids and found that only DHEA was associated with their measurement modality of well-being.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8878326
Barrett-Connor, in the Journal of the American Geriatric Society, 1999, published data from one of my favorite study groups, the Rancho Bernardo longitudinal survey database. Plasma levels of estradiol, testosterone, estrone, androstenedione, cortisol, and DHEA were measured. A study of 699 women, aged 50-90 demonstrated a significant inverse correlation between DHEA levels and mood scores on the Beck Depression Inventory. These findings were age independent. DHEA had better predictive value than any other hormone evaluated in the study.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10366167
In addition to correlation between DHEA levels and mood, interventional studies have demonstrated efficacy of DHEA supplementation and measures of mood. A small prospective pilot study published by Bloch in 1999, looking at “mid-life dysthymia,” found that sixty percent of their subjects had responded to DHEA monotherapy at the end of the 6-week treatment period compared with 20% in the placebo group. The symptoms that improved most significantly were anaerobia, loss of energy, lack of motivation, emotional "numbness," sadness, inability to cope, and worry.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10376113
Wolkowitz, in 1999, demonstrated similar findings:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10200751
Schmidt, in the Archives of General Psychiatry, February 2005, demonstrated the utility of DHEA as mono-therapy for both major and minor mid-life onset depression in both men and women. DHEA produced a greater than 50% reduction in depression scores for 50% of subjects, vs. a 23% score reduction rate for placebo. Treatment subjects also outperformed the placebo group in terms of self reports of sexual function.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15699292
Just as Co-Q10 levels are affected by statin therapy, and demonstrate the importance of maintaining levels of endogenous compounds that can be iatrogenically affected, the same may hold true for DHEA during pharmacologic therapy for depression. In one study (Deuschle, in Neuropsychobiology, 2004) showed that amitryptiline therapy was associated with a 39% reduction in circulating DHEA levels. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15365225
DHEA and Autoimmune/Inflammatory Disorders
Some disease states outside the typical hormonal realm have been demonstrated, as well. There are many literature citations dealing with disease state and DHEA levels in addition to demonstrating some clinical benefit associated with DHEA replacement. Patients with SLE/Lupus have been shown to have diminished levels of DHEA. (Small, but representative study) http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11575596
This low DHEA state also correlates with diseases specific pathophysiology. For example, SLE patients demonstrate an increase in terminal differentiation of peripheral blood mononuclear cells, which correlates with disease activity, and exposure to DHEA was associated in vitro with a diminishment in the pathological differentiation patterns.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11780316
SLE patients demonstrate lower levels of DHEA than in normal controls, these diminished levels are associated with specific disease enhancing pathology, and low levels are also associated with loss of “pathology preventing” signaling between immune system cells, as well. Interferon gamma (IFN g) is associated with negative feedback inhibition of immune response in normal controls, and DHEA facilitates this signaling. In SLE, normal DHEA levels and signaling effects are lost, with the subsequent change favoring an exaggerated immune response rather than a normal one.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11403266
The above findings would lead one to predict a therapeutic role for DHEA in the treatment of SLE, and this has been shown to be the case. Studies have repeatedly demonstrated the utility of DHEA supplementation in terms of reduction of symptom scores or reduction in accompanying medication requirements. This effect has been greatest in patients with mild or moderate disease, but DHEA has had clinical value as part of multi-drug therapy in severe cases and may also be associated with mitigating the osteoporosis associated with long-term corticosteroid regimens:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12428233
DHEA has small utility in severe SLE but is associated with possible reduction in steroid requirements and decreases steroid related bone loss: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10342710
DHEA suppresses IL-10 secretion by T-cells in patients with SLE.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15547086
The effect of DHEA on IL-10 secretion demonstrates the substantial “crossover” that is seen in the pathophysiology of inflammatory disorders. It has also been demonstrated that DHEA supplementation has disease score modulating effects on other inflammation based disorders such as Crohn’s Disease and Ulcerative Colitis.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12562454
In addition to SLE, DHEA therapy may be of utility in Rheumatoid Arthritis, Polymyalgia Rheumatica, and some aspects of Sjogren’s Syndrome, but there are only preliminary reports of diminished DHEA secretion or function and scattered early speculative reports regarding DHEA therapy. These are tidbits only, and are not definitive, in any regard.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12508908
DHEA may aid in regulation of some atopic inflammation:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9248620
In addition to affecting disease physiology, DHEA may also be associated with minimizing the negative effects of other therapies. Even low dose inhaled corticosteroid therapy in the management of asthma can be associated with an increase in osteoporosis risk, and these therapies are associated with diminished DHEA levels, as well: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15132725
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9718197
This effect has been shown for other steroid requiring disorders, as well:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12404198
Which leads us to…
DHEA and Bone
Even in otherwise normal patients, low DHEA levels correlate with lower bone mineral density (BMD) and osteoporosis risk, making it yet another disease risk marker for loss of BMD.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15665656
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9650403
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8578930
Females in the lowest quartile for DHEA levels have been demonstrated to be at increased fracture risk compared to normal risk:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10934651
Conversely, well maintained DHEA levels are associated with retained BMD
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15207889
Per our usual discussions, an association between level and risk is not sufficient validation for therapy, and DHEA supplementation has been shown to improve BMD in men with osteoporosis. Over a 12 month study period, BMD increased in the lumbar spine and femoral neck by nearly 3%.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11940375
The same types of findings have been seen in female replacement studies, with increases in BMD and decreases in markers of bone resorption.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9329392
The segue from DHEA and bone to other organ systems can be found in the next reference. Interleukin 6 (IL-6), is a pro-inflammatory cytokine whose presence is associated with inhibition of osteoblast function – leading to declines in BMD. IL-6 levels are also associated with other potential disease risk, such as heart disease and dementia. Lower DHEA levels are associated with an elevation in IL-6 levels, and replacement is associated with declines in IL-6. So, in this study by Straub in JCEM, 1998, we have results in terms of a disease risk marker that is multi-system in terms of risk and in terms of risk reduction.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9626133
Another aside, done sotto voce. There are null result studies for DHEA, as well. When reviewing the literature, it may be best to take search results in an electoral fashion and add up the number of studies or total number of subjects studied, and then determine one’s opinion. The following references show no effect on BMD of DHEA, reminding us that perhaps universal dosing is not always an optimal method of treating a patient group, nor is treating without titration to a given level vs. using even a dose/weight method. These results also act as a reminder of what we promise, and not all patients will receive all the benefits of a given intervention. As one additional note, these results also point out the lack of any negative outcome, which is useful in determined the safety part of the safety and efficacy of a given intervention.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8452124
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8144828
So, transition to…
DHEA and the Brain
Some studies have demonstrated a correlation between Alzheimer’s Disease (AD) and DHEA levels. Again, these results exist within the context of multiple risk factors, but there is a statistical inverse correlation between DHEA levels and AD.
Weill-Engerrer found a significant negative correlation between the levels of cortical beta-amyloid peptides DHEA in the hypothalamus.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12414884
Another study found higher cortisol levels, lower DHEA levels, and a higher cortisol/DHEA ratio in subjects with AD than is seen in control subjects.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11314741
Yet another study demonstrated diminished circulating DHEA levels AD subjects.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9844034
In patients with pre-existing AD, those with higher DHEA levels performed better on cognitive function testing.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10373337
Here comes the important part, and why we insist on more than correlation between a finding and assuming that altering that finding will have an effect. AD patients treated with DHEA showed no improvement on cognitive measures.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12682308
Neither did studies on normal older people.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11405958
At present, I would not try to claim any certain value for DHEA in the course of preventing or treating AD. Given the large variability of lesion number and precise location of AD plaques or pathology, different study results may only be expressing findings for the myriad sites of AD damage and anatomical rather than metabolic consequences with regard to AD and its effect on the brain/HPA/adrenal axis.
Rat studies have demonstrated a neuroprotective effect of DHEA on experimentally induced oxidative damage to neurons, so this may one day show a role for DHEA in cytoporotection. This may also overlap with the clinical benefit of DHEA in autoimmune disorders.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10095075
DHEA and Erectile Dysfunction
As a member of the androgen family, DHEA has been looked at regarding its possible usefulness in the treatment of erectile dysfunction (ED). The ED studies are not exhaustive in their attention to detail…DHEA has been shown to be lower in men with ED. Keep in mind that many times, this is in conjunction with low levels of all androgens or may have been measured without consideration for other androgen levels. Needless to say, if monotherapy works, however, then effective is still effective.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10792095
DHEA supplementation was shown to improve ED in subjects with hypertension, but no mention was made as to which, if any, medications were also involved, and whether any specific class of anti-hypertensive was more or less likely to contribute to the incidence of ED or the outcome of DHEA intervention.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11585284
DHEA: General Considerations
DHEA levels in patients who subsequently developed prostate cancer over a 12 year period, had DHEA levels 11-12% below those of controls.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8318873
Today’s final words on DHEA belong to women. DHEA supplementation was shown in one 12 month study on postmenopausal women to increase HDL by 11%, decrease LDL by 11%, and improve insulin sensitivity, at a dose of 25 mg/day. Again, global reduction in markers of disease risk.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11581005
Finally, a “who knows what this will mean for the future” study on the effects of DHEA on postmenopausal women showed a change in T-cell profile from CD4+ to CD56+ (NK) cell profiles in association with inhibition of IL-6 and T cell mitogenic responses with a simultaneous dramatic increase in NK cell cytotoxicity. These effect were consistent with an “antioncogenic” profile.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8267058
Alan P. Mintz, M.D., is Chief Medical Officer, Chief Executive Officer, and co-founder, Cenegenics® Medical Institute. Dr. Mintz has completed the AMA/PRA Level 4 Classification, Parts 1 & 2, Tutorial Training in Age Management Medicine jointly sponsored by the Cenegenics Medical Institute and The Foundation for Care Management. A University of Chicago graduate, Dr. Mintz earned the Degree of Doctor of Medicine from the University of Illinois - School of Medicine. He went on to serve as a physician with the United States Navy, prior to postgraduate training in radiology. Dr. Mintz is a Diplomate of the American Board of Radiology, including nuclear medicine and radiation therapy. Dr. Mintz was appointed chairman of the Department of Radiology for several Chicago-area hospitals and remains an adjunct professor for the Center for Cardiovascular Research, at Northeastern Illinois University. He previously held the positions of chief executive officer, president and co-founder at the world’s largest radiology management company. Thanks to his professional expertise and guidance, Cenegenics Medical Institute (with the joint sponsorship of Foundation for Care Management) has been recognized by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education to physicians.
Feature Article
Cultural Stress: Neuroendocrine-Induced Physiological Aberrant Remodeling—the Modern Pathophysiological Phenotype
Ron Shane, Ph.D.
Abstract
The psychological community once regarded cultural stress as being problematic in a cognitive context, and some theorists have argued that it was the etiological basis for a variety of affective disorders. Moreover, molecular-oriented neurobiologists realized that an allostatic upregulation of the hypothalamic hormone CRF negatively impacts the majority of an organism’s homeostatic physiological processes, as well as its optimal morphological nature. Chronic upregulation of cortisol dramatically alters the transcriptional activities of all of the cells in the body, drastically changing their set points, which transduce specific genetic networks to produce a matrix of tropic factors that significantly modify or structurally remodel the organism’s macrocellular systems. Thus, the overall phenotypical gestalt of the organism is pathologically altered in terms of is physiological dynamics and heuristic structure. Modern man’s cultural strategies have not only unfavorably changed the body’s myriad of physiological systems, but have also aberrantly modified the dispositional sentient nature of the human organism.
Biological scientists, for the preceding hundred years, have marveled how specific cellular systems deviate from their quintessential genotypical gestalt. These researchers have been disinclined to succinctly delineate how modern culture has caused today’s human phenotype to go awry from its optimal homeostatic nature. The intent of this paper is to demonstrate that the current social matrix is the etiological basis for the human animal’s pathophysiological phenotypical remodeling.
Clinical medical science has adroitly documented the particular way humans have become physiologically less optimally homeostatic and robust, even though the average life span has increased by over twenty-five years. In other words, medical research is enabling pathophysiology to flourish, and man’s heuristic quality of life to become more diminutive. For example, diabetes II many Americans over fifty who, without the wide variety of available pharmaceutical agents, would all succumb to this fatal disease. Diabetes II, unlike its counterpart, diabetes I, which affects younger humans who genetically inherit compromised pancreatic beta cells, however the former condition brought about by years of aberrant tissue remodeling. Furthermore, Diabetes II, in many instances, can be rectified by overall lifestyle changes, which include improving dietary regime and stringent program of exercise. Heart disease, like diabetes II, is a deleterious condition which is induced by non-optimal homeostatic lifestyles. In 1999, the estimated direct and indirect costs of heart disease were $99.8 billion dollars(1). This devastating malady can be prevented or mitigated by altering the patterns of cellular phenotypical expression. Many medical practitioners are privy to the fact that the American way of life is neither neurophysiologically edifying nor propitiously homeostatic. There appears to be a schism between optimal physiology and adherence to a social edicts. Is western man’s cognitive epistemology challenging his species’s ideal biological praxis or genetic architecture? Moreover, this question is far asunder from the molecular dynamics of cellular machinations which are the research concerns of today’s biological scientific community. In contrast, this paper will assiduously examine whether man’s social milieu is inducing humans to express an overall phenotype that is profusely pathological or antithetical with this organism’s optimal physiology. Biological science, like all forms of commercial enterprise, is involved with the procurement of either governmental or private monies in order to conduct multi-million dollar research endeavors. It would be politically incorrect to convincingly demonstrate that our cultural circumstances are resulting in a bevy of physiological maladies. Medically oriented scientists appear to vouchsafe this thematic conundrum to the sociologist or others who, unfortunately, do not understand organ pathophysiology or molecular biology. Koob and Le Moal’s 2001 review does push neurobiology into the cultural polemics and theater aberrant phenotypical optimal physiology.
Endocrinologists are keenly aware that chronic upregulation of CRF or the downstream activation of cortisol will result in a diverse array of pathological conditions for certain phenotypes. In recent years, several signal transduction pathways have been identified which, when turned on by the upregulation of cortisol, will cause structural changes in specific cell types. Koob (1999 A) alludes to the fact that Sterling and Eyer’s concept of allostasis or when there is an elevation of an organism’s CRF homeostatic set points is a principle factor which endogenous emotional disorders as well as various kinds of deleterious cellular changes(2). Sterling and Eyer (1988) argue that cultural stress is certainly maladaptive to the human organism’s physiological dynamics(3). These researchers implicitly suggest that today’s social milieu is thoroughly disruptive, biologically speaking, to man’s overall well-being.
Darwinian theory is predicated upon the idea that organisms have evolved the most suitable genetic disposition, with respect to their environmental context; and also express a propitious/edifying phenotype. Moreover, the phenotype in most instances is the optimal realization of the genotype. However, modern man has become, in biological terms, a parody of this paradigm.
There doesn’t seem to be any other organisms which celebrates a non-optimal physiological manifestation of its genotype except for man. It is a conundrum as to why this species has evolved a cultural milieu that biologically rewards the aberrant phenotypical expression of its genotype. Contarino, Heinrichs and Gold (1999) have demonstrated that increased levels of CRF in animal models are involved emotional maladies, as are “several CRF-related gene products in the pathophysiology of a variety of complex behavioral disorders.”(4) These authors write the following regarding emotional pathology and CRF upregulation:
In Darwinian terms, the Homo sapiens became a prominent hominoid species roughly 43,000 years ago. And the unique genetic disposition of this species was wondrously adaptable to thrive in a myriad of naturalistic landscapes. In other words, this species was optimally physiological to or could superbly survive in almost all kind of Earthly environmental context. Humans, unlike other animals, exhibit a greater possibility of phenotypical adaptation or what social anthropologists denote as cultural learning strategies. Modern man’s social context has progressively become disassociated from the Earthly sphere. Mammalian organisms express genetic physiological proclivities which enable these species to continue to thrive in specific physical environments; and likewise those succinct animals exhibit an unique quintessential homeostasis. Conversely, man’s social evolution is not only sequestering his species from nature’s edifying fervidness, but more importantly creating a cultural landscape, biologically speaking, that has made the human more pathophysiological and less optimally robust. Thus, man’s cultural reality reinforces pathophysiological condition as compared to nature’s landscape which would necessitate that all humans should be superbly optimally physiological. Contemporary humans need more exogenous pharmaceutical agents in order to physically exist. And phenotypes that are less robust and biologically compromised through the marvel of 21st century medical science are afforded the opportunity to survive. Moreover, the medical profession is based on a paradigm of pathophysiology, not optimal homeostasis. The theoretical portion of a medical doctor’s training regime consists of analyzing a variegated array of disease models or homeostasis having gone awry. There isn’t any significant discussion of taking the biological sciences’ theoretical query into the realm of superlative homeostasis. Furthermore, pharmaceutical companies are not allowed or would have the Promethean task of getting a drug approved which would heighten a person’s sense of well-being or physical prowess. For example, in most instances, a M.D. who prescribes an oral anabolic agent to a patient who is physically impoverished as a result of his torpid emotional nature would be operating in a manner contradictory to FDA guidelines. In short, neither the medical community nor pharmaceutical companies are inclined to develop or employ exogenous drugs to take modern man’s diminutive physiological condition to a more superlative level.
There is a colossal amount of literature written on the devastation of modern culture as it positively effects man’s physiological well-being. According to the U.S. Surgeon General’s Department of Health and Human Services 1996 report, 59% of American adults are thoroughly sedentary.(6) It is certain that with this society’s dependence upon the computer, this figure most likely is even more elevated at present. Unfortunately, this society’s addition to electronic technology is having deleterious results on the salubrious machination of the human body. Homo sapiens’s physiological systems did not genetically evolve to be thoroughly sedentary. In other words, on the molecular level, proteins and enzymes necessary for the maintenance of cellular well-being are aberrantly down-regulated without the body dynamically enacting edifying movement sequences.
Darwin stated that all organisms have genetically evolved to auspiciously thrive in a certain environmental context, and this implicitly involves that the specific entity has achieved an overall sense of homeostatic well-being. No other animal except for Homo sapiens can flourish even though there is in this species a predominant phenotypical decline toward pathophysiology. Modern society is becoming increasing disassociated from the heuristic marvel of man’s intrinsic physiological dynamics. Is technological sophistication correlated with a decrement in emotional and physiological salubriousness? Many epidemiological studies have documented that Americans in the preceding forty years have become lethargic, obese, inactive, depressed, anxious and emotionally dysphoric. Scientific researchers will not receive governmental funding if they demonstrate an etiological relationship between cultural factors and pathophysiology. Conversely, molecular biologists will beget private and federal funding for research on exogenous agents which will mitigate these physiological maladies.
Henry David Thoreau, nearly two hundred years ago and prior to the renaissance in genetic and molecular biology, argued that industrialized societies are ruinously divesting the human spirit of its quintessential majesticness. 21st century neurobiologists have no way of quantifying this bucolic and rhapsodic poetic declamation. In contrast, it is without question that contemporary man’s phenotypical physiology has been adversely affected by his opulently predominant social milieu. In other words, medical researchers keenly now comprehend that the body’s multitudinous tissues undergo extensive tropic remodeling as a consequence of interacting with a succinct environmental context. The majority of social scientists believe that our cultural reality primarily affects the way in which we reason and think, as well as our essential response configurations. Moreover, for these scholars, social learning principally influences and modifies the neocortex’s cognitive machinations. This antiquated view of biological adaptation has fallen into disrepute. Neurobiologists like Antonio Damasio and George Koob have empirically demonstrated that environmental circumstances affect the cellular maintenance processes and developmental activities in all of an organism’s variegated physiological systems. For example, cells in the kidney through chemical-signals evoked by their nephrons speak to the multifaceted neurons of the central nervous system; and they in turn communicate back to peripheral tissue structures. The mammalian systemic circulation is a watery thoroughfare of cumulative interaction between all cells of the physical body. And even though neuroscientists do not yet comprehend the biochemical mechanisms of learning, they postulate that it involves enzymatic and transcriptional alteration in specific neurons or gilia cells, and these molecular changes would likewise affect a plethora of other cellular networks. The black box of the mind presided over by the homunculus purely privy to environmental factors is as absurd of a paradigm as the sun revolving around the Earth. The entire body is succinctly remodeled as a function of its interfacement and interaction with man’s pervasive environmental milieus.
There is compelling evidence that the chronic upregulation of CRF expression in particular phenotypes causes anxiety and depression.(7) Heilis and Koob (1994) write, “In several studies, increased concentrations of CRF have been reported in the cerebrospinal fluid of patients with major depression.” Furthermore, not only does an over-expression of CRF correlate or most likely bring about a plethora of mood and anxiety disorders, but likewise induces aversive molecular transcriptional activities within the body’s cellular networks. Multitudinous contemporary cultural factors induce an incremental secretion of CRF or the aberrant turning on of the body’s neuroendocrine stress system, leading to a pathophysiological remodeling within a diverse array of tissue structures. For example, it has been shown that the over-expression CRF alters the concentration levels of neurotransmitters in succinct regions of the central ner344vous system. Isogawa and Akiyoshi found that the upregulation of CRF modifies serotonin and noradrenalin profiles. Isogawa and Akiyoshi, 2000 state that “stress induced anxiety may be produced by increasing norepinephrine and serotonin in the hippocampus after activating CRF.”(8) It is evident that CRF activates molecular pathways which are associated with stimulating a vast array of transcriptional activities and gene products that are likely involved with modifying the structural integrity of the cell as well as its functional maintenance processes. Thus, incremental changes in CRF aberrantly effects the morphological nature of cells in the central nervous system as well tissue sites throughout the body. Furthermore, these negatively affected cells will likewise be comprised in terms of their routine and necessary molecular machinations. Societal stressful devastation is further amplified by the fact that CRF pejoratively influences other essential peptides like NPY, and Urocortin and various neurotransmitters, and each of those neural ligands are involved in either turning on and off many transcriptional factors where the overall nature of cellular mechanisms are then profoundly effected by CRF upregulation.
Technological innovations and the incremental acceleration of the economy is dogmatically heralded as being magnificent. Medical scientists are rather reluctant and wretchedly demure in terms of reviewing if today’s social reality does actually promote well-being. Conversely, it behooves these researchers not to probe with ardour into this sphere of inquiry as it is western culture’s “sacred cow” or the sacrosanct Pandora’s box where it is now politically incorrect to question the propitious reverence of today’s culture. Is the venerated market place, the Charnel House, that embodies enfettered human spirits? Is physiological malaise the object viable outcome of the information age; and it is likely like a virus which disrupts cellular transcription and translation that today’s environmental milieu is pathophysiological to many of our molecular processes?
Philosophers who analyze the contemporary social reality of 21st century and its intriguing technology question whether the newest electronic devices which are readily usurped into our culture are intrinsically beneficial to man’s physiological dynamics and emotional well-being. In the preceding thirty years, corporations have made billions of dollars selling cell phones, home computers, internet services, software and other electronic accoutrements. However, has this technology been auspicious and edifying to man’s emotional and physiological nature? Are humans working less hours relishing in more leisure, enjoying improved physiological health, reduced dependence on extraneous pharmaceutical agents and emotionally more mirthful? Conversely, the members of western society are working more feverishly with less time for endogenously intrinsic activities, and these individuals are not physiologically robust, as well as besieged by a myriad of negative affective maladies. What then is the intrinsic merit of this innovative technology to the common person. More over, there doesn’t seem to be any edifying and quintessential benefit of these innovative artifices. However, they have in synergistic manner been deleterious to man’s optimal homeostasis. Does anyone care whether man’s emotional prodigious quality of life has been mortified in the preceding century. The pharmaceutical industry appears to be responding to this problematic scenario by creating more exogenous agents which allay the central nervous system’s new biochemical perturbation that are produced by man’s culturally evolving urban existence. For example, several companies are developing CRF agonists which will competitively bind to CRF receptors prohibiting the over expression of corticotropin releasing hormone which is the current cause of a diverse array of emotional maladies. Moreover, presently countless Americans are being prescribed cocktails of psychotropic agents to enable them to cope with this society’s ever increasing tumultuous emotional exigencies. Unfortunately, the pharmaceutical companies have not yet developed what Huxley referred in his novel Brave New World which he labeled as a “soma.” This single agent hypothetically could mitigate the aversive psychological maladies induced by the problematic nature of western culture. According to Huxley, this fictitious agent soma didn’t have any side effects, and upon orally ingesting this drug the individual was consumed by extolling exhilaration. In contrast, from anti-psychotics to that of the anti-depressants agents they all produce considerable side-effects and do not like soma engender emotional euphoria. Furthermore, psychiatrists are becoming more inclined to prescribe several of these psychotropic drugs to their patients. Koob and Lemoal, 2001 and others, have demonstrated that the over expression of CRF down regulates the endogenous release of enkephalins in the central nervous system’s meso-limbic region. Thus, society’s menacing stressful factors are inciting havoc to man’s homeostatic neural biochemical profiles. The 19th century British poet Shelley, in his poem Queen Mab depicts an utopian culture in which man’s emotional nature is optimally edified; however, today’s society is like a virulent weeded garden where the human psyche is nurtured to pathophysiology or aberrantly remodeled.
Moreover, there are a myriad of medically trained clinician who are professing a lifestyle of optimal homeostasis rather than that of pathophysiology. These innovative physicians are involved and proponents of anti-aging medicine. Dr. Karlis Ullis argues in his book “Age Right” that it is necessary for individuals to actively take control of their biological health(9). This physician asserts that each person can evade the tumultuous overall devastation of a pathophysiological existence. Dr. Ullis points out that exercise or a variegated approach to physical training, stress reduction, proper nutrition, and invigorating mystical artistry must be arduously executed in order to achieve a lifestyle of superb well-being. Many physicians in the United States are focusing their practice of medicine away from pathophysiology to that of quintessential salubriousness. Unfortunately, these medical practitioners are not dealing with the younger generation, but are primarily treating middle age Americans who have allowed their phenotype to be come pathophysiological. Its seems intuitively simplistic that if you exercise two hours a day, engage in a stretching routine, perform cardiovascular activities, execute strength resistance movement sequences, and enact sophisticated highly coordinated motor movement actions all which should comprise a person’s training regime, as well as eat a diet rich in proteins, fruits vegetables, complex carbohydrates, but avoid low fats and excessive sugars, and evade poignant stressors, a person will evolve an optimally physiological phenotype. It is estimated only 5% of Americans over 50 have lived lives where they have been compliant to a superlative physiological mode of existence as put forth in the preceding statement. The essential question is why 95% of the adults are adverse to that pattern of living when as it has been documented to be prodigious to their physiological well being. The Homo sapien’s genetic architecture suggests that this organism has predominantly evolved not to be sedimentary, obese, chronically stressed, metaphysically/artistically dissipated, and emotionally distraught.
Today’s physician who is seeing older Americans whose phenotype is pathophysiological can attempt to rectify or design programs to radically alter their patient’s lifestyle; however, to the client’s chagrin, their body’s diverse cellular systems have morphologically adapted or been remodeled to a lifestyle which is homeostatically aberrant. Moreover, anyone with a basic comprehension of sociological dynamics knows it is nearly impossible to dramatically alter this current cultural trend toward negative tissue remodeling; and this society needs to be somehow judiciously educated to a lifestyle which is optimally physiological. Exercise physiologists have in histological terms compared the differences between muscle cells of athletes and sedentary persons, and have found a plethora of significant differences. For example, athletes have denser capillary beds, greater mitochondria, a distinctive sarcomere band structural symmetry, a stronger and more developed actin and myosin as well as expressing a different array of growth factors. It is evident that athletically conditioned striated skeletal muscle tissue is more optimally physiological to a person and auspiciously effects a countless array of other variegated cell types. These specialized striated muscle cells based on their succinct activities express an unique matrix of enzymatic proteins, and these biochemical signals will profoundly impact other distinctive molecular and cellular systems process. The body’s biochemical waterways are effected and poignantly modified by man’s enigmatic environmental milieu.
In summary, it has already been discussed that chronic over-activation of the CRF system is the etiological basis of deleterious emotional conditions or the diverse array of affective disorders that besieges today’s humans. The cultural factors which are inducing social stress are not being attenuated but in fact appear to be to more incessant in their ravagement by the incremental preponderance of man’s emotional morbidity. The thrust of this review is not scrutinize modern Homo sapiens emotional dismay, but to demonstrate that contemporary humans must commence the task of somehow ameliorating their direful cultural course which is resulting in overall pathophysiology and embrace optimal homeostasis. The nineteenth century British romantic poet, Shelly asserted in his final poem, “The Triumphant of Life” that western culture’s delirium dance is macabrely tragic where the human psyche is divested of its ecstatic fecundity and mercurial reverie. There is some indication that social stress during pregnancy significantly impacts the emotional nature of the offspring in animal models. Kaiser and Sachser 2001 suggest that “instability of the social environment during pregnancy and lactation had distinct and not yet described effects on the behavior and endocrine system of the male offspring.(10) It is likely as with animal paradigms human mothers whose stress system are disregulated where their homeostatic set points have been allostatically aberrantly elevated will profusely perturb their children’s CRF axis. In other words, her progeny will be more inclined to anxiety disorders and affective maladies. This social scenario seems to indicate that this epidemic preponderance toward affective disorders is being further amplified as mothers are negatively effecting their progeny’s neurophysiological emotion well-being. Thus, children reared by mothers who have up-regulated CRF levels and associated baneful affective disorders should manifest even more debilitating emotional maladies than their progenitors; and these neuroendocrine abnormalities will likewise predispose those persons to express other pathophysiological conditions. Has today’s culture become man’s nemesis? United States government is spending billions of dollars in fighting the war on drugs, heart disease, obesity, diabetes II, and emotional disorders, but those judicators of our social reality are not inclined to comprehend that those abject physiological outcomes are being engendered by succinct cultural factors. Sociologically speaking, these seemingly sagacious legislators respond to these aversive pathologies by championing and lauding pharmaceutical companies effects to produce more efficacious exogenous agents to allay these physiological morbidities, and to create more restrictive dismal legislation. This culture’s moribund fury and squalid enthrallment is allowed to propitiously blossom unencumbered by impeding dissension. There is convincing empirical evidence that today’s social milieu is causing humans to be consumed by affective maladies as well as on a cellular level is the etiological basis for their diverse tissue to be phenotypically remodeled in a pathological manner. Thus, man’s overall optimal homeostasis is hindered by our pervasive societal machinations.
Ron Shane, Ph.D. is a post-doctoral research scholar at the University of California at San Diego, working in the field of neuroendocrinology and psychology. Dr. Shane received his master’s and doctorate degrees from the University of California at Santa Barbara in Sociology and Social Psychology. He has been involved in post-doctoral studies with in the field of Neuroendocrinology and Optimal Physiology and the Biological Basis of Consciousness and Neurobiology. Dr. Shane has done post doctoral training in the disciplines of renaissance mysticism, neurobiology, neuroscience, western medicine and cross cultural shamanism. He is a certified master of Kundalini Yoga and an IF international instructor and expert fifth degree black belt of Tae Kwon Do. He was a former college strength and fitness coach and has written books and articles on martial arts, Taoism, Esoteric Yoga, Cross training regimes, western integrative medicine, endocrinology, neuroscience and optimal health.
Industry News
Dramatic Changes in U.S. Aging Highlighted in New Census, NIH Report
Impact of Baby Boomers Anticipated
Thursday, March 9, 2006, 10:35 a.m. EST
The face of aging in the United States is changing dramatically -- and rapidly, according to a new U.S. Census Bureau report, commissioned by the National Institute on Aging (NIA). Today’s older Americans are very different from their predecessors, living longer, having lower rates of disability, achieving higher levels of education and less often living in poverty. And the baby boomers, the first of whom celebrated their 60th birthdays in 2006, promise to redefine further what it means to grow older in America.
The report, 65+ in the United States: 2005, was prepared for NIA, a component of the National Institutes of Health (NIH) at the U.S. Department of Health and Human Services, to provide a picture of the health and socioeconomic status of the aging population at a critical time in the maturing of the United States. It highlights striking shifts in aging on a population scale and also describes changes at the local and even family level, examining, for example, important changes in family structure as a result of divorce.
“The collection, analysis, and reporting of reliable data are critical to informing policy as the nation moves ahead to address the challenges and opportunities of an aging population,” says NIA Director Richard J. Hodes, M.D. “This report tells us that we have made a lot of progress in improving the health and well-being of older Americans, but there is much left to do.”
Among the trends:
The health of older Americans is improving. Still, many are disabled and suffer from chronic conditions. The proportion with a disability fell significantly from 26.2 percent in 1982 to 19.7 percent in 1999. But 14 million people age 65 and older reported some level of disability in Census 2000, mostly linked to a high prevalence of chronic conditions such as heart disease or arthritis.
The financial circumstances of older people have improved dramatically, although there are wide variations in income and wealth. The proportion of people aged 65 and older in poverty decreased from 35 percent in 1959 to 10 percent in 2003, mostly attributed to the support of Social Security. In 2000, the poorest fifth of senior households had a net worth of $3,500 ($44,346 including home equity) and the wealthiest had $328,432 ($449,800 including home equity).
Geographically, Florida (17.6 percent), Pennsylvania (15.6 percent) and West Virginia (15.3 percent) are the “oldest” states, with the highest percentages of people aged 65 and older. Charlotte County, Fla. (34.7 percent) gets top honors among counties, and McIntosh County, N.D. (34.2 percent) ranks second.
Higher levels of education, which are linked to better health, higher income, more wealth and a higher standard of living in retirement, will continue to increase among people 65 and older. The proportion of Americans with at least a bachelor’s degree grew five-fold from 1950 to 2003, from 3.4 percent to 17.4 percent, and by 2030, more than one-fourth of the older population is expected to have an undergraduate degree. The percentage completing high school quadrupled between 1950 and 2003, from 17.0 percent to 71.5 percent.
As the United States as a whole grows more diverse, so does the population aged 65 and older. In 2003, older Americans were 83 percent non-Hispanic White, 8 percent Black, 6 percent Hispanic and 3 percent Asian. By 2030, an estimated 72 percent of older Americans will be non-Hispanic White, 11 percent Hispanic, 10 percent Black and 5 percent Asian.
Changes in the American family have significant implications for future aging. Divorce, for example, is on the rise, and some researchers suggest that fewer children and more stepchildren may change the availability of family support in the future for people at older ages. In 1960, only 1.6 percent of older men and 1.5 percent of women aged 65 and older were divorced. But by 2003, 7 percent of older men and 8.6 percent of older women were divorced and had not remarried. The trend may be continuing. In 2003, among people in their early 60s, 12.2 percent of men and 15.9 percent of women were divorced.
“The social and economic implications of an aging population—and of the baby boom in particular—are likely to be profound for both individuals and society,” says Census Bureau Director Louis Kincannon. “The 65+ in the United States report helps us to understand these dramatic changes so we can examine how they may impact families and society.”
The 65+ report is a project of the NIA’s Behavioral and Social Research Program, which supports the collection and analyses of data in several national and international studies on health, retirement, and aging. The program’s director, Richard M. Suzman, Ph.D., suggests that, with five years to go before the baby boom turns 65, “Many people have an image of aging that may be 20 years out of date. The very current portrait presented here shows how much has changed and where trends may be headed in the future.”
65+ lead author, Victoria A. Velkoff, Ph.D., chief of the Aging Studies Branch at the U.S. Census Bureau, noted the variations among today’s older adults and those of the future. “People 65 and over are a very diverse group. How they experience aging depends on a variety of interacting factors—from gender and race/ethnicity to health, education, socioeconomic and family circumstances. 65+ in the United States: 2005 depicts this heterogeneity, which will further expand as this population doubles in size over the next 25 years.”
The report was prepared by Dr. Velkoff and co-authors Wan He, Ph.D., Manisha Sengupta, Ph.D., and Kimberly A. DeBarros of the Population Division, U.S. Census Bureau.
The 243-page compendium examines in detail five key areas: growth of the older population (changes in age and racial/ethnic composition), longevity and health (life expectancy and causes of death), economic characteristics (income and household wealth), geographic distribution (by population and race) and social and other characteristics (marital status, living arrangements and voting patterns).
The report covers a wide range of topics and timelines, pulling together data from Census 2000 and previous censuses, nationally representative surveys and recent population projections. In addition to the data compiled by other federal agencies, including the National Center for Health Statistics and the U.S. Department of Housing and Urban Development, the report also includes statistics from the Current Population Survey; American Housing Survey; National Health Interview Survey; National Health and Nutrition Examination Survey; Survey of Income and Program Participation; and the Health and Retirement Study.
The public can view and also download the report at www.census.gov.
The Census Bureau serves as the leading source of quality data about the nation's people and economy. For more information, visit the Census Bureau website at www.census.gov.
The NIA is the lead federal agency conducting and supporting basic, biomedical and behavioral and social research on aging and the special needs and problems of older people. For more information, visit the NIA website at www.nia.nih.gov or call toll free 1-800-222-2225. ###
Appendix
SELECTED HIGHLIGHTS FROM 65+ IN THE UNITED STATES: 2005
The older U.S. population is growing rapidly as baby boomers age, and more people are living longer:
The first baby boomers will turn 65 in 2011, and people aged 65 and over are projected to represent 20 percent of the total U.S. population in 2030 compared with 12 percent in 2003.
Average life expectancy at birth in 2000 was 76.9 years; females could expect to live an average of 5.4 years longer than men.
About 80 percent of centenarians are women.
The United States is relatively young compared with other developed countries. Despite its aging, the United States has a lower proportion of adults aged 65 and older than that of most countries in Western Europe.
In general, older people in the United States are healthier than in the past, with lower rates of disability. Still, a significant proportion suffers from health problems and chronic disease, and causes of death have not changed dramatically:
Death rates for heart disease are declining among people 65 years and over; in general, heart disease and cancer are the leading causes of death within this population, with death rates varying by age, sex, and race.
About 80 percent of seniors have at least one chronic health condition, and 50 percent have at least two chronic health conditions, which often lead to disability. Arthritis, hypertension, heart disease, diabetes and respiratory disorders are some of the leading causes of activity limitations among older people.
The rates of disability and functional limitation among the older population have declined substantially over the past two decades; about one in five older Americans report having chronic disability.
Data comparing people aged 65 to 74 in 1988-94 and 1999-2000 show a startling rise in the percentage of people considered obese -- in men, the proportion grew from about 24 to 33 percent and in women from about 27 percent to 39 percent.
The older population is growing more in some geographic regions than in others, and is concentrated in metropolitan areas:
Between 1990 and 2000, the largest proportionate increases in the older population were mainly in the West, particularly in the Mountain States, and in the South, particularly in the South Atlantic states.
In 2000, nine states—California, Florida, New York, Texas, Pennsylvania, Ohio, Illinois, Michigan and New Jersey—had more than 1 million residents aged 65 and over.
The 10 counties with the highest percentage of people age 65 and over in 2000 were:
In 2000, almost three-fourths of Hispanics aged 65 and up lived in California, Texas, Florida and New York, and nearly two-thirds of older Asians lived in the West.
Three out of four older people lived in metropolitan areas in 2000.
There is a strong correlation between education and health. Older adults are increasingly more educated, and this continuing trend could have a positive effect on the health of older people in the future:
By 2030, more than one-fourth of the older population is expected to have at least a bachelor’s degree, and the percentage of older women with a bachelor’s degree will likely double, from 13.4 percent in 2003 to 27.8 percent in 2030.
Substantial educational differences by race and Hispanic origin exist, despite the overall rise in educational attainment within the older population. In 2003, 76 percent of older non-Hispanic whites, 70 percent of older Asians, 52 percent of older Blacks, and 36 percent of older Hispanics had completed high school.
The gender gap in completion of a college education will narrow in the future because men and women in younger cohorts are earning college degrees at roughly the same rate.
Older adults in the United States are far less likely to live in poverty today than in decades past, although poverty rates vary by group:
Between 1959 and 2003, the proportion of people aged 65 and over who lived below the poverty line decreased from 35 percent to 10 percent.
In 2003, older women were more likely than older men to be living in poverty (13 percent compared with 7 percent).
Older non-Hispanic whites (8 percent) were less likely than older Blacks (24 percent) and older Hispanics (20 percent) to be living in poverty in 2003.
People aged 65 and older are less likely to be in the labor force today than in decades past, but many continue to work:
Labor force participation rates of men aged 65 and older fell dramatically over the past several decades, from 46 percent in 1950 to 19 percent in 2003. Rates for older women did not change statistically during that time period.
By 2020, people aged 55 and over are expected to make up 20.3 percent of the labor force, up from 15.1 percent in 2003.
As employed men and women get older, their likelihood of working part-time increases. In 2003, about half of employed men aged 70 and over and almost two-thirds of employed women aged 70 and over worked part-time.
Social Security continues to provide the largest share of income for many older Americans.
The social characteristics of older people vary greatly, often by age within the post-65 group:
Three-quarters of the 10.5 million older Americans living alone in 2003 were women. The proportion varies greatly by age, with 29.6 percent aged 65 to 74, 47.6 percent aged 75 to 84, and 57 percent aged 85 and older living alone.
In 2000, 4.5 percent of people aged 75 to 84 and 18.2 percent of those 85 and older lived in nursing homes. About three in four older nursing home residents are women.
The majority of men aged 65 to 84 were veterans, reflecting the high proportion of men who served in the military during World War II.
People aged 65 and older consistently vote in higher proportions than other age groups. In 2000, 67.6 percent of the older population, compared with 49.8 percent of those aged 25 to 44, said they voted; of all the votes cast that year, some 20 percent were by people age 65 and older.
Industry News
Botox, Get Ready for a Rival
Cosmetic maker Medicis teams with a European company to develop and market a competing anti-wrinkle treatment
Reloxin Agreement Between Ipsen and Medicis Becomes Effective
Sources: Red Herring and Morningstar
PARIS and SCOTTSDALE, Ariz., March 14 and 20, 2006—Facial cosmetic medicine maker Medicis Pharmaceutical said it struck a deal with French drug manufacturer Ipsen Promesses to develop and market Reloxin, a potential competitor to blockbuster drug Botox.
The deal was subject to the closing of Botox-maker Allergan’s $3.2 billion acquisition of cosmetic treatment and breast implant developer Inamed.
Inamed currently holds the rights to Reloxin. But in December, the company said it planned on terminating them to avoid any regulatory issues as it goes forward with its buyout by Allergan.
Like Botox, Reloxin is a botulinum toxin used to smooth lines on the face. The product in development needs to receive federal approval to join the U.S. facial aesthetics industry, which brought in more than $400 million in sales in 2005, according to Millennium Research Group.
And if Medicis can bring Reloxin to market, the company will attempt to position itself as an alternative to the No. 1 cosmetic procedure in the U.S., Botox injections. In 2005, the wrinkle eraser was used in 3.29 million procedures.
Medicis has been trying to add Reloxin to its portfolio since March 2005, when the company first made a play for the technology through a $2.8-billion acquisition bid for Inamed. But the deal was called off after Allergan came in with a higher offer.
The failed deal was not a total loss for Medicis. “Reloxin was the most important component of the transaction,” said Medicis CEO Jonah Shacknai at the JPMorgan Annual Healthcare conference in San Francisco back in January.
At the same meeting Mr. Shacknai said Medicis had the opportunity to increase its offer but declined. He said Medicis wanted Reloxin and the company was certain it would fall out of the mix if Inamed and Allergan merged. Medicis was right.
Ipsen and Medicis announced on March 20 that the agreement whereby Ipsen Ltd, a wholly-owned subsidiary of Ipsen ("Ipsen"), grants Aesthetica Ltd, a wholly-owned subsidiary of Medicis ("Medicis"), rights to develop, distribute and commercialize Ipsen's botulinum toxin product in the United States, Canada and Japan for aesthetic use by physicians is now effective. The product is commonly referred to as Reloxin(R) in the U.S. aesthetic market and Dysport(R) for medical and aesthetic markets outside the U.S. The product is not currently approved for use in the U.S. Ipsen has recovered its rights to Reloxin(R) at the time of this announcement.
Medicis has paid to Ipsen $90.1 million in consideration for the exclusive distribution rights in the United States, Canada and Japan and has agreed to pay an additional $26.5 million upon successful completion of various clinical and regulatory milestones, $75.0 million upon the product's approval by the U.S. Food and Drug Administration and $2.0 million upon regulatory approval of the product in Japan, amounting to a total of $193.6 million. Ipsen will manufacture and provide the product for Medicis for the term of the agreement, which extends to September of 2019. Ipsen will receive a royalty based on sales and a supply price, the total of which is equivalent to approximately 30% of net sales as defined under the Agreement. Medicis will be responsible for all remaining research and development costs associated with obtaining the product's approval in the territory.
Additionally, Medicis and Ipsen have agreed to negotiate and enter into an agreement relating to the exclusive distribution and development rights of the product for the aesthetic market in Europe, and subsequently in certain other markets. Under this agreement, Medicis would pay upfront and other milestone payments linked to the development and approval of Ipsen's botulinum toxin Type A product in aesthetic indications as well as royalties based on net sales. Ipsen would manufacture and supply the product to Medicis. The terms of this agreement will be disclosed after its execution, which is expected to occur on or before April 15, 2006. If this agreement is not entered into by April 15, 2006, Medicis will be obligated to make an additional payment to Ipsen in connection with the USA, Canada and Japan agreement.
"We are very pleased to entrust the development and distribution of Reloxin(R) to a leading expert of the aesthetic field such as Medicis," said Jean-Luc Belingard, Chairman and Chief Executive Officer of Ipsen. "We were looking for a partner who could optimize time to market for Reloxin(R), with a quality complementary product offering and a strong presence in the USA. Medicis, with its world leading RESTYLANE(R) dermal filler, its leading sales force and image with both dermatologists and plastic surgeons and its previous knowledge of Reloxin(R), is our preferred partner in order to maximize the penetration of Reloxin(R) in the U.S. market. Our combined products will offer a very compelling alternative to practitioners in the aesthetic medicine field."
"We are very pleased to have reached this agreement with Ipsen on terms favorable to both organizations," said Jonah Shacknai, Chairman and Chief Executive Officer of Medicis. "We continue to be very impressed with the sophisticated development and manufacturing programs established by Ipsen and the clinical outcomes resulting from Ipsen's efforts to date. We are enthusiastic about having the opportunity to partner with Ipsen on this late-stage development product with a sizeable commercial potential. We stand ready to deploy the necessary resources to bring this product to the U.S. market and maximize its opportunity in one of the largest segments in the aesthetic market. We have recognized for some time the value of supplying physicians through our leading sales force Ipsen's botulinum toxin product and the world's leading dermal filler RESTYLANE(R), and we are very pleased that it has finally become a reality."
© 1993-2006 Red Herring, Inc.
© Copyright 2006 Morningstar, Inc.
Industry News
Estrogen Therapy Doesn't Cause Breast Cancer: Study
But treatment isn't risk-free, so women should consult their doctors, experts say
Source: HealthDay News
April 11, 2006
Estrogen therapy on its own does not increase the risk of breast cancer in postmenopausal women, an extensive new study has found.
The findings, from the Women's Health Initiative (WHI), stand in stark contrast to previous results from the estrogen-plus-progestin arm of the trial. That study was halted in 2002, three years ahead of schedule, when evidence showed a higher risk of not only breast cancer, but blood clots, stroke and heart attack.
While the new report found no evidence that estrogen therapy causes breast cancer, other research has found the therapy can cause blood clots in postmenopausal women, potentially leading to cardiovascular problems. So, women need to consult with their doctors to weigh the benefits and risks of estrogen therapy, experts said.
"People have to stop thinking all hormones are the same," said Marcia L. Stefanick, professor of medicine at Stanford University's Stanford Prevention Research Center and chairwoman of the WHI steering committee and executive committee. "There is no contradiction."
"The current findings are good news for women on estrogen but it doesn't help women on the combined therapy," Stefanick added.
The new findings appear in the April 12 issue of the Journal of the American Medical Association.
Outside experts also considered the new finding good news for women struggling with menopausal symptoms, which can include hot flashes, vaginal dryness and loss of energy.
"It does provide reassurance to patients taking estrogen that it might not be as bad as everyone assumed," said Dr. Jennifer Wu, an obstetrician/gynecologist with Lenox Hill Hospital in New York City. "Many patients have such severe symptoms that they really don't want to stop taking their estrogen."
Added Dr. Hugh Taylor, associate professor of obstetrics and gynecology at Yale University School of Medicine: "This study is great news for women, especially those entering menopause. We have seen confusing and conflicting information that has led to exaggerated and unfounded fears of estrogen. I think the rollercoaster ride is over."
Taylor spoke at an April 7 teleconference sponsored by Wyeth Pharmaceuticals, which makes Premarin and Prempro, hormone therapies intended to mollify symptoms of menopause.
The Women's Health Initiative is a 15-year-long examination of the causes and prevention of diseases affecting older women. So far, the research has produced a complicated picture of the risks and benefits related to hormone therapy.
An earlier set of WHI results found that estrogen therapy did not diminish or increase the risk for heart disease, while leaving open the possibility that it might reduce the risk in women aged 50 to 59.
The estrogen-only portion of the trial -- the subject of the new findings -- was also stopped early (in 2004) because of an increased risk of stroke and blood clots and no reduction in the risk of coronary heart disease. Preliminary data showed no risk of breast cancer; the new findings represent the final data.
For this study, the researchers analyzed data on 10,739 postmenopausal women aged 50 to 79 at 40 clinical centers throughout the United States. The participants were randomly chosen to receive either estrogen or a placebo and underwent mammography screenings and clinical breast exams at the beginning of the study and annually thereafter. The data was collected between 1993 and 1998.
All the women in the study had undergone a hysterectomy. Estrogen alone cannot be given to women with a uterus because of an increased risk of uterine cancer. Instead, these women take estrogen plus progestin to mitigate the risk. "The addition of progestin is to protect the uterus against the estrogen, but if you don't have a uterus you can take just estrogen," Stefanick explained.
After an annual follow-up of 7.1 years, women in the estrogen group had a slightly and statistically non-significant reduction in their risk for invasive breast cancer (20 percent lower) and total breast cancer (18 percent lower).
When they were diagnosed with breast cancer, however, women in the estrogen group tended to have larger tumors that were more likely to have spread to the lymph nodes. This suggests that estrogen may lower the risk of smaller cancers but not larger ones, the researchers said.
Women who had a low risk of breast cancer -- such as no family history or no benign breast disease -- had fewer breast cancers while on estrogen, while those with a higher risk had more breast cancers.
Overall, though, the evidence seems to indicate that estrogen therapy does not contribute to a higher risk of breast cancer.
"These data are pretty good evidence that estrogen therapy is relatively safe for breast cancer," Stefanick said.
The true existence of breast cancer among the study participants still needs to be double-checked, cautioned Dr. William T. Creasman, J. Marion Sims professor of obstetrics and gynecology at the Medical University of South Carolina. Creasman also spoke at the Wyeth news conference. "We don't know if these are all breast cancers," he said. "We're taking the word of the individuals who reviewed the slides initially and that, we know, has a margin of error."
But other factors, such as the increased risk for blood clotting, still need to be taken into account when prescribing hormone therapy.
In fact, a study published Monday in the Archives of Internal Medicine found that estrogen therapy appears to increase the risk of blood clots in the veins of postmenopausal women who have had their uterus removed.
"The paradigm of treating most women who are symptomatic with the lowest effective dose for the shortest amount of time makes sense," Taylor said.
In a prepared statement, Dr. Joseph Sanfilippo, president of the American Society for Reproductive Medicine, cautioned that "women must make decisions about the use of hormone therapy in conjunction with their physician. Each woman is different and her symptoms and risk factors will be different."
Industry News
Hormone Can Predict Pulmonary Hypertension, Risk of Death
BNP serves as a marker in people with serious lung disease, study says
Robert Preidt
Source: HealthDay News
March 31, 2006
Levels of a hormone called brain natriuretic peptide (BNP) can predict the presence of pulmonary hypertension and the risk of death in people with serious lung disease.
That's the conclusion of a German study in the April issue of the American Journal of Respiratory and Critical Care Medicine.
BNP, a hormone produced by the heart, is activated by various cardiovascular diseases. Healthy people have low levels of BNP in their blood. But BNP levels begin to increase if the heart is forced to work harder over an extended period of time.
In this study, researchers measured BNP levels in 176 people with a variety of pulmonary diseases. The patients also underwent lung function testing, right heart catheterization, and a six-minute walk test.
"In the absence of significant left heart disease, BNP serves as a marker of an increased workload in the right heart originating from idiopathic pulmonary arterial hypertension," Dr. Juergen Behr, division of pulmonary diseases at Ludwig Maximilians University in Munich, said in a prepared statement.
In the 10 months following the study, 31 of the patients (18 percent) died of cardiopulmonary causes.
"Patients who died during the follow-up period more frequently had elevated BNP levels and prominent pulmonary hypertension with significantly impaired right heart function," Behr said.
He and his colleagues concluded that BNP is a prognostic marker and screening parameter for significant pulmonary hypertension in patients with chronic lung disease.
Industry News
Tests Predict Long-Term Kidney Risk
Blood, urine screens can spot the dangers decades early
Robert Preidt
Source: HealthDay News
April 12, 2006
Simple blood and urine tests in middle age may help predict a person's risk of developing end-stage kidney disease over the next 25 years.
U.S. researchers say the tests include the urine "dipstick" test (which detects protein in urine) and a blood test to estimate kidney function called the "estimated glomerular filtration rate" (eGFR).
For this study, a team from the Minneapolis Veterans Affairs Medical Center analyzed data on nearly 13,000 men enrolled in a long-term study of cardiovascular disease prevention. The men were 35 to 57 years old when the study began in 1972-1975. Follow-up data was available through 1999.
Over 25 years, 1.7 percent of the men developed end-stage renal disease (ESRD) or died of kidney disease.
Men who had more than a trace amount of protein in their urine in middle age -- as detected by the dipstick test -- had triple the risk of ESRD at follow-up. Men with an even stronger positive result for protein in the urine were 15 times more likely to develop ESRD.
The study also found that ESRD risk more than doubled in men with abnormally low eGFR function.
Men with abnormal readings on both the dipstick test and eGFR were 41 times more likely than men with normal results on both tests to suffer ESRD, the researchers noted.
Age, smoking, blood pressure, low levels of HDL ("good") cholesterol, and blood sugar levels were other factors that predicted ESRD risk, the study authors said.
