Dr Colin Holloway
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Antibiotic overuse might be why so many people have allergies
Posted by Dr Colin Holloway
September 28, 2015 6.43pm AEST
Avery August
Professor of Immunology and Chair of the Department of Microbiology and Immunology, Cornell University
Avery August receives funding from National Institutes of Health.
The Conversation is funded by CSIRO, Melbourne, Monash, RMIT, UTS, UWA, ACU, ANSTO, ANU, Canberra, CDU, CQU, Curtin, Deakin, ECU, Flinders, Griffith, the Harry Perkins Institute, JCU, La Trobe, Murdoch, Newcastle, UQ, QUT, Swinburne, Sydney, UNDA, UNE, UniSA, UNSW, USC, USQ, UTAS, UWS, VU and Wollongong.
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Too many? Mark Blinch/Files/Reuters
Scientists have warned for decades that the overuse of antibiotics leads to the development of drug-resistant bacteria, making it harder to fight infectious disease. The Centers for Disease Control and Prevention estimates that drug resistant bacteria cause 23,000 deaths and two million illnesses each year.
But when we think of antibiotic overuse, we don't generally think of allergies. Research is beginning to suggest that maybe we should.
Allergies are getting more and more common
In the last two to three decades, immunologists and allergists have noted a dramatic increase in the prevalence of allergies. The American Academy of Asthma, Allergy and Immunology reports that some 40%-50% of schoolchildren worldwide are sensitized to one or more allergens. The most common of these are skin allergies such as eczema (10%-17%), respiratory allergies such as asthma and rhinitis (~10%), and food allergies such as those to peanuts (~8%).
This isn't just happening in the US. Other industrialized countries have seen increases as well.
This rise has mirrored the increased use of antibiotics, particularly in children for common viral infections such as colds and sore throats. Recent studies show that they may be connected.
Antibiotics can disrupt the gut microbiome
Why would antibiotics, which we use to fight harmful bacteria, wind up making someone more susceptible to an allergy? While antibiotics fight infections, they also reduce the normal bacteria in our gastrointestinal system, the so-called gut microbiome.
Because of the interplay between gut bacteria and the normal equilibrium of cells of the immune system, the gut microbiome plays an important role in the maturation of the immune response. When this interaction between bacteria and immune cells does not happen, the immune system responds inappropriately to innocuous substances such as food or components of dust. This can result in the development of potentially fatal allergies.
Exposure to the microbes at an early age is important for full maturation of our immune systems. Reducing those microbes may make us feel cleaner, but our immune systems may suffer.
Do more microbes means fewer allergies?
Research done in Europe has shown that children who grow up on farms have a wider diversity of microbes in their gut, and have up to 70% reduced prevalence of allergies and asthma compared to children who did not grow up on farms. This is because exposure to such a wide range of microbes allows our immune systems to undergo balanced maturation, thus providing protection against inappropriate immune responses.
In our attempts to prevent infections, we may be setting the stage for our children to developing life-threatening allergies and asthma.
For instance, a study from 2005 found that infants exposed to antibiotics in the first 4-6 months have a 1.3- to 5-fold higher risk of developing allergy. And infants with reduced bacterial diversity, which can occur with antibiotic use, have increased risk of developing eczema.
And it's not the just the antibiotics kids take that can make a difference. It's also the antibiotics their mothers take. The Copenhagen Prospective Study on Asthma in Childhood Cohort, a major longitudinal study of infants born to asthmatic mothers in Denmark, reported that children whose mothers took antibiotics during pregnancy were almost twice as likely to develop asthma compared to children whose mothers did not take antibiotics during pregnancy.
Finally, in mice studies, offspring of mice treated with antibiotics were shown to have an increased likelihood of developing allergies and asthma.
More prescriptions for antibiotics might mean more allergies. Gary Cameron/Reuters
Why are antibiotics overused?
Physicians and patients know that overusing antibiotics can cause big problems. It seems that a relatively small number of physicians are driving overprescription of antibiotics. A recent study of physician prescribing practices reported that 10% of physicians prescribed antibiotics to 95% of their patients with upper respiratory tract infections.
Health care professionals should not only be concerned about the development of antibiotic resistance, but also the fact that we may be creating another health problem in our patients, and possibly in their children too.
Parents should think carefully about asking physicians for antibiotics in an attempt to treat their children's common colds and sore throats (or their own), which are often caused by viral infections that don't respond to them anyway. And doctors should think twice about prescribing antibiotics to treat these illnesses, too.
As we develop new antibiotics, we need to address overuse
As resistant bacteria become a greater problem, we desperately need to develop new antibiotics. The development process for a new antibiotic takes a considerable amount of time (up to 10 years), and drug companies have previously neglected this area of drug development.
Congress has recognized that antibiotic overuse is a major problem and recently passed the 21st Century Cures bill. This bill includes provisions that would create payment incentives from Medicare for hospitals that use new antibiotics.
But this approach would have the perverse effect of increasing the use of any new antibiotics in our arsenal without regard for whether bacterial resistance has developed. This would not only exacerbate the problem of resistance, but potentially lead to more people developing allergies.
Congress should consider more than just supporting increased development of new antibiotics, but also address the core problem of overuse.
This may stave off the further development of antibiotic resistant bacteria and reduce the trend of increasing development of allergies.
How we're arming the immune system to help fight cancer
The fourth pillar: how we're arming the immune system to help fight cancer
January 7, 2016 11.43am AEDT
Executive Director Cancer Research Head, Cancer Immunology Program Professor, Peter MacCallum Cancer Centre
Joseph Trapani receives funding from the National Health and Medical Research Council, Government of Australia, The Wellcome Trust, UK, Cancer Council Victoria, Australian Cancer Research Foundation and the Victorian Cancer Agency. Professor Trapani is currently Executive Director Cancer Research and Head of the Cancer Immunology Program at Peter MacCallum Cancer Centre, Melbourne, Australia. He is also a member of the Executive (Board) of the Cancer Council Victoria and Chair of it's Medical and Scientific Committee.
The past 40 years have seen a significant improvement in cancer survival. In the 1970s, only one cancer patient in three made it through the first five years after diagnosis.
The corresponding figure today is around 70%, and exceeds 85% for some cancers that were previously fatal.
What's more, the trend of roughly 1% increased survival for every year that passes, is being maintained with our growing understanding of "cancer biology" – that is, what causes cancer and how cancer cells grow and spread.
New treatment options have flowed directly from this knowledge.
Conventional therapies: the three pillars
Until a century ago, the only hope of curing cancer was surgical removal. But two new treatments emerged in the middle of the 20th century: radiation therapy and chemotherapy. These remain indispensable in mainstream treatment.
Further progress in these disciplines is limited by their inability to discriminate between cancer cells and important normal cells. Patients undergoing radiotherapy and chemotherapy usually lose hair, feel extreme nausea and are prone to life-threatening infections due to reduced numbers of white blood cells.
This century's approaches to developing new forms of chemotherapy are radically different from a generation ago. Our new understanding has identified specific weaknesses that can be targeted by "designer" therapies, and treatments can increasingly be personalised to the cancer of any one individual.
Because these new drugs (which are a type of personalised medicine) specifically attack cancer cells, they have far fewer side effects than conventional chemotherapy.
Just as exciting as these is the realisation that a patient's own immune system is a powerful agent in defeating cancer. Immune-based strategies are now in advanced clinical trials in dozens of studies around the world.
Checkpoint blockade and adoptive immunotherapy are two examples of the fourth and newest pillar of cancer therapy, the first such advance in 50 years.
Checkpoint blockade
When a virus infects us, the immune system responds by activating "killer cells" to multiply and rid the body of the invader. When the danger has passed, a brake is applied to the immune system. Remaining extra immune cells die, swelling settles and things return to normal.
Many cancers have learnt to use this "brake" mechanism to "switch off" immune killer cells trying to eliminate them. Turning the switch back on with specific antibody therapies can wipe out enormous numbers of cancer cells.
Antibodies are naturally occurring proteins generated by the immune system to neutralise viruses and toxins. Scientists are now engineering new, therapeutic antibodies that mimic natural ones.
In checkpoint blockade, an antibody is given to a patient through an intravenous infusion. The antibody binds either to the cancer or immune cell to prevent the cancer cell from turning on the brake.
The prototype therapy is the antibody ipilimumab (Yervoy), reported to have saved the life of former Liberal Party national president Ron Walker from late-stage melanoma.
But as Yervoy and similar agents activate the immune system, one drawback is that it can become over-activated in some patients, and start attacking normal tissues. This can be managed with anti-inflammatory therapies.
Agents similar to Yervoy work in some cases of lung and kidney cancer. Many other forms of cancer are currently being trialled.
Checkpoint blockade is not only capable of clearing enormous tumours, but the results appear durable. Once awakened, the immune response to cancer generally persists, which is wonderful news.
But because not everyone is able to spontaneously raise killer cells against their cancer, not every patient benefits from checkpoint blockade treatment. Removing the brake in such patients has no effect.
We now have a way around this problem. Adoptive immunotherapy can provide patients with "tailored" killer cells.
Adoptive immunotherapy
This second strategy uses a process called apheresis, where a machine harvests just the killer cells from a person's blood, while returning all the other cells to the patient.
Then, in special labs built to extraordinary levels of cleanliness to avoid contamination, the killer cells receive a gene that codes for a receptor to guide them back to the patient's cancer.
With the receptor, the cells become killer cells the patient previously lacked, called chimeric antigen receptor T cells (CAR T cells). After 10 or 12 days, when enough CAR T cells have been grown in the lab, they are given back to the same patient through a vein.
They are now able to "home" to cancer cells anywhere in the body.
Once in contact with cancer, they do three things. First, they kill cancer cells directly. Second, they divide making more killer cells at the site of the cancer. And third, they set up inflammation in the tumour so the immune response spreads.
Adoptive immunotherapy is close to becoming "standard" for certain types of cancer where other available therapies have been exhausted.
Several successful trials have been reported using CAR T cells in cases of advanced acute lymphocytic leukemia (ALL), the most common cancer in children. In one such recent trial, a child considered close to death was successfully treated with CAR T cells prepared from immune cells of an unrelated person.
At present, immune-based therapies are relatively expensive. CAR T cell treatment, for example, costs about the same as a bone marrow transplant. But cost will fall as the technologies for cell production improve.
It is safe to say there has never been more hope for cancer cures. Ever.
Why Doesn't My Endocrinologist Know All of This?
I have always wondered why specialists are so anti natural thyroid and Bioidentical hormones, in spite of the overwhelming evidence (as given on my web-site) of the benefits they give and patients preferences to natural treatments. It is a blind spot that specialist have. I have discussed this in previous blogs. I frequently get patients who have been on the rounds of gynecologists, endocrinologist and others, who still don't feel right. As in the email below, they will often respond to the natural hormones. This also applies to Low Dose Naltrexone, (LDN), which I am getting some amazing results in many auto-immune disorders. It is letters such as the one below, and the positive feedback I get every day from patients, that keeps me going in the work I do.
Here is the email, from Julie (not her real name)
Dear Dr Holloway
I just wanted to give you some feedback on how the new thyroid medication is working for me. I can't begin to tell you how much better I feel. I had been taking levothyroxine for years and it made absolutely no difference whatsoever to any of my symptoms. I felt absolutely miserable for years and years. Since taking the natural thyroid, however, I just cannot believe the difference and now have a taste of what it must feel like to feel normal and healthy. The debilitating fatigue has gone, I now sleep well every night (it is blissful to sleep properly), and my body temperature has normalised (I used to feel the cold so bitterly it actually hurt). I can't thank you enough for caring enough and being open-minded enough to explore alternative medications to levothyroxine. If it weren't for you, I would still feel as sick and awful as I have felt for the past two decades rather than feeling so much better.
Reprinted with permission from The National Academy of Hypothyroidism: http://www.nahypothyroidism.org.
A question often raised by patients is: "Why doesn't my physician know about the inaccuracies and limitations of standard thyroid tests?" The reason is that the overwhelming majority of physicians (endocrinologists, internists, family practitioners, rheumatologists, etc.) do not read medical journals. When asked, most doctors will claim that they routinely read medical journals, but this has been shown not to be the case. Many reasons exist, but it comes down to the fact that doctors do not have the time — they are too busy running their practices. The overwhelming majority of physicians rely on what they have learned in medical school and on consensus statements by medical societies, such as the Endocrine Society, the American Association of Clinical Endocrinologists or the American Thyroid Association, to direct treatment decisions.
Historically, relying on a consensus statement to treat or not to treat a particular patient has been shown to result in poor care and, as such, society consensus statements and practice guidelines are considered to be worst level of evidence in support of a particular therapy or treatment. A number of organizations, including the World Health Organization and others, have ranked the strength and accuracy of various types of evidence used in the medical decision process. In all scoring systems, the highest strength of evidence is randomized control trials and meta-analyses, with lower scores for other types of evidence. All grading systems place consensus statements and expert opinion by respected authorities (societies) as the poorest level of evidence, because historically they have failed to adopt new concepts and treatments based on new knowledge or new-found understanding demonstrated in the medical literature (1-6).
For instance, a recent study published in the 2009 Journal of American Medical Association studied the evidence supporting the practice guidelines and consensus statements published by the American College of Cardiology and the American Heart Association. It was found that only 11% of the recommendations, practice guidelines and consensus statements were based on quality evidence and over half were based on poor quality evidence that was little more than the panel's opinion. The review also found that even the strongest (Class 1) recommendations, which are considered medical dogma, cited as a legal standards and often go unquestioned as medical fact, were only supported by high quality evidence 19% of the time and not revised based on new evidence (6).
Similarly, the Endocrine Society, the American Association of Clinical Endocrinologists and the American Thyroid Association also have a long history of guidelines and recommendations that are not supported by the medical literature and fail to adjust or abandon recommendations when new understanding and knowledge contradicts their recommendations. A case in point is the recommendation by these societies that a normal TSH adequately rules out thyroid dysfunction, despite massive amounts of literature that demonstrate this not to be the case (see Diagnosis of Hypothyroidism) or that T4 only replacement is adequate for most patients. A doctor who simply follows outdated society treatment guidelines that relies on a simple laboratory test and ignores the clinical aspects of a patient is not practicing evidence-based medicine. (1-7). Such doctors may be adequate as lab technicians, but as doctors and clinicians they fall short (1-7). This method of practice is consistently rebuked as improper and poor medicine, but has become the standard used by a large percentage of endocrinologists and physicians who feel medicine can be related to simply reading "normal" or "abnormal" in a laboratory column.
Discussing the lack of scientific basis of most medical society's consensus statements and treatment guidelines in Internal Medicine News, Dr. Diana Petritti, states, "Expert opinion and consensus statements can be quite misleading when used as the basis for a practice. Expert opinions imply that there is something that the experts know that clinician doesn't know. I don't think it's always appreciated that it's only opinion. There is a tendency to make guidelines and recommendations seem authoritative. I believe that physicians think that there is a great deal more behind authoritative recommendations than there might be when you lift the lid of the box and see what's underneath(8)."
There has been significant concern by health care organizations and medical experts that physicians are placing too much reliance on consensus statements and failing to learn of new information presented in medical journals. Thus, they lack the ability to translate this new information into treatments for their patients. The concern is that doctors fail to practice evidence-based medicine, erroneously relying on what they have previously been taught and on "expert" societies instead of changing treatment philosophies based on new information as it becomes available. This is especially true for endocrinological conditions, where physicians are very resistant to changing old concepts of diagnosis and treatment — despite overwhelming evidence to the contrary — because it is not what they were taught in medical school and endocrinology residency.
This concern is particularly clear in an article published in the New England Journal of Medicine entitled "Clinical Research to Clinical Practice: Lost in Translation" (9). The article was written by Claude Lenfant, M.D., Director of National Heart, Lung and Blood Institute, and it is well supported. He states that there is great concern that doctors continue to rely on what they learned 20 years before and are uninformed about scientific findings. According to Dr. Lenfant, medical researchers, along with public officials and political leaders, are increasingly concerned about physicians' inability to translate research findings in their medical practice to benefit their patients. He says that very few physicians learn about new discoveries from reading medical journals or by attending scientific conferences; thus, they lack the ability to translate new knowledge in the field into enhanced treatments for their patients. He states that a review of past medical discoveries reveals how excruciatingly slow the medical establishment is to adopt novel concepts, noting that even simple methods to improve medical quality are often met with fierce resistance. "Given the ever-growing sophistication of our scientific knowledge and the additional new discoveries that are likely in the future, many of us harbor an uneasy, but quite realistic suspicion that this gap between what we know about disease and what we do to prevent and treat them will become even wider. And it is not just recent research results that are not finding their way into clinical practice; there is plenty of evidence that 'old' research outcome have been lost in translation as well (1)."
Dr. Lenfant discusses the fact that the proper practice of medicine involves the combination of medical knowledge, intuition and judgment and that physicians' knowledge is lacking because they don't keep up with the medical literature. He states that there is often a difference of opinion among physicians and reviewing entities, but that judgment and knowledge of the research pertaining to the patient's condition is central to the responsible practice of medicine. "Enormous amounts of new knowledge are barreling down the information highway, but they are not arriving at the doorsteps of our patients. (9)."
These thoughts are echoed by physicians who have researched this issue as well, such as William Shankle, M.D., Professor, University of California, Irvine. He states, "Most doctors are practicing 10 to 20 years behind the available medical literature and continue to practice what they learned in medical school….There is a breakdown in the transfer of information from the research to the overwhelming majority of practicing physicians. Doctors do not seek to implement new treatments that are supported in the literature or change treatments that are not (10)."
This view is echoed by the Dean of Stanford University School of Medicine who states that in the absence of translational medicine the delivery of medical care would remain stagnant and uninformed by the tremendous progress taking place in science and medicine (11).
This concern has also received significant publicity in the mainstream media. An example is an article by Sidney Smith, M.D., former president of the American Heart Association, published in 2003 in the Wall Street Journal entitled Too Many Patients Never Reap the Benefits of Great Research. Dr. Smith is very critical of physicians for not seeking out available information and applying that information to their patients, arguing that doctors feel the best medicine is what they've been doing and thinking for years. They discount new research, Dr. Smith says, because it is not what they have been taught or practiced, and they refuse to admit that what they have been doing or thinking for many years is not the best medicine. He states, "A large part of the problem is the real resistance of physicians…; many of these independent-minded souls don't like being told that science knows best, and the way they've always done things is second-rate (12)." The National Center for Policy Analysis also expresses concern for the lack of ability of physicians to translate medical therapies into practice (13).
A review published in The Annals of Internal Medicine found that there is clearly a problem of physicians not seeking to advance their knowledge by reviewing the current literature, believing proper care is what they learned in medical school or residency and not basing their treatments on the most current research. The review found that the longer a physician is in practice, the more inappropriate and substandard the care (14). Thus, it is not a surprise that the scientific evidence as expressed in the literature is often opposite to what is continually repeated as dogma by most physicians and those considered to be "experts."
Another example is a study published in the Journal of the American Medical Informatics Association (15). In reviewing the study, the National Institute of Medicine reports that there is an unacceptable lag between the discovery of new treatment modalities and their acceptance into routine care: "The lag between the discovery of more effective forms of treatment and their incorporation into routine patient care averages 17 years." (16) In response to this unacceptable lag, the Business and Professions Code passed an amendment relating to the healing arts. This amendment — CA Assembly Bill 592; An Act to Amend Section 2234.1 of the Business and Professions Code — states: Since the National Institute of Medicine has reported that it can take up to 17 years for a new best practice to reach the average physician and surgeon, it is prudent to give attention to new developments not only in general medical care but in the actual treatment of specific diseases, particularly those that are not yet broadly recognized [such as the concept of tissue hypothyroidism, chronic fatigue syndrome and fibromyalgia] (17).
The Principals of Medical Ethics adopted by the American Medical Association in 1980 states that a physician shall continue to study, apply, and advance scientific knowledge, make relevant information available to patients, colleagues, and the public (18). This has, unfortunately, been replaced with a goal of providing merely "adequate" care. The current insurance reimbursement system in the United States fosters this thinking, as the worst physicians are financially rewarded by insurance companies. While it is true that the best physicians are continually fighting to provide cutting edge treatments and superior care that the insurance companies deem not medically necessary, even these physicians eventually get worn down and are forced to capitulate to the current system that promotes substandard care.
This was clearly demonstrated in a study published in the March 2006 edition of The New England Journal of Medicine entitled "Who is at Greater Risk for Receiving Poor-Quality Health Care." The study found that the majority of individuals received substandard, poor-quality care, and that there was no significant difference among different income levels or whether or not the individual was covered by insurance. It used to be the case that only those in low socioeconomic classes without insurance received poor-quality care. But insurance company restrictions on treatments and diagnostic procedures have made the same poor care afforded to those of low socioeconomic status the new standard-of-care for society at large (19). An example of this is a physician's failing to spend the time to adequately assess a potential hypothyroid patient and instead simply does a TSH test.
Most physicians will satisfy their required amount of continuing medical education (CME) by going to a conference a year, usually at a highly desirable location that has skiing, golf, boating, etc. Physicians are rarely monitored as to whether or not they actually showed up for the lectures or went skiing instead. One must also understand that the majority of conferences organized by medical societies are in fact sponsored by pharmaceutical companies. These payments by pharmaceutical companies are called unrestricted grants, so that the society has free reign to do what they want with the money and thus can claim there is no influence of lecture content by the companies. The problem, however, is that if the society wants to continue getting these "unrestricted" grants, they must think twice about providing content that the sponsoring pharmaceutical company might disapprove of. Consequently, ground breaking research that goes against the status quo and does not support the drug industry receives little attention.
Evidence-based medicine involves the synthesis of all available data when comparing therapeutic options for patients. Evidence-based medicine does not mean that data should be ignored until a randomized control trial of a particular size and duration is completed. A physician who tries to avoid the need of being a physician and is fine with just being a technician or health care provider will adamantly defend the "one-size fits all" method of diagnosis and treatment. But the best doctors who truly practice evidence-based medicine and not merely the perception of such will not rely on consensus statements to best provide their patients. Instead of relying on old dogma, the best physicians will seek out and translate both basic science results and clinical outcomes to decide on the safest, most efficacious treatment for their patients. Further, the best physicians will continually assess the current available data to decide which therapies are likely to carry the greatest benefits for patients and involve the lowest risks.
1. Amerling R, Winchester JF, Ronco C, "Guidelines have done more harm than good,"Blood Purification 2008;26;73-76.
2. Guirguis-Blake J, Calonge N, Miller T, Siu A, Teutsch S, Whitlock E., "Current processes of the U.S. Preventive Services Task Force: refining evidence-based recommendation development". Ann. Intern. Med 2007; 147(2):117–22.
3. Barton MB, Miller T, Wolff T, et al. "How to read the new recommendation statement: methods update from the U.S. Preventive Services Task Force," Ann. Intern. Med 2007;147(2):123–7.
4. CEBM > EBM Tools > Finding the Evidence > Levels of Evidence http://www.cebm.net/levels_of_evidence.asp#levels.
5. Atkins D, Best D, Briss PA, et al. (2004). "Grading quality of evidence and strength of recommendations," BMJ 2004;328 (7454):1490.
6. Tricoci P, Allen JM, Kramer KM, et al. Scientific evidnce underlying the ACC/AHA clincal practice guidelines. JAMA 2009;301(8):831-841.
7. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS (January 1996). "Evidence based medicine: what it is and what it isn't". BMJ 312 (7023): 71–2.
8. Zoler ML. Half of cardiac guidelines are not evidence based: Expert opinion under scrutiny," Internal Medicine News 2009;42(7):1,8.
9. Lenfant C, New England Journal of Medicine, "Clinical Research to Clinical Practice: Lost in Translation" 2003;349:868-874.
10. William Shankle, M.D., Key Note Presentation. International Conference on the Integrative Medical approach to the Prevention of Alzheimer's Disease. Oct 11, 2003.
11. Phillip Pizzo , M.D., Stanford Medical Magazine. Stanford University Scholl of Medicine.
12. Begley S., "Too Many Patients Never Reap the Benefits of Great Research" Wall Street Journal, September 26, 2003.
13. "Science Know Best," Daily Policy Digest. National Center for Policy Analysis, Sept 26, 2003.
14. Niteesh. C et al., "Systematic Review: The relationship between Clinical experience and quality of health care," Annals of Internal Medicine.
15. Balas, E.A. 2001," Information Systems Can Prevent Errors and Improve Quality," Journal of the American Medical Informatics Association 8 (4):398-9.
16. National Institute of Medicine Report, 2003b
17. BILL NUMBER: AB 592 AMENDED BILL TEXT; AMENDED IN ASSEMBLY APRIL 4, 2005, INTRODUCED BY Assembly Member Yee FEBRUARY 17, 2005 . An act to amend Section 2234.1 of the Business and Professions Code, relating to healing arts.
18. The Principals of Medical Ethics adopted by the American Medical Association in 1980.
19. Asch SM et al., "Who is at Greater Risk for Receiving Poor-Quality Health Care," New England Journal of Medicine 2006; 354:1147-1155.
Thyroid Hormone Transport
I had a big response to my blog on thyroid problems recently ("How accurate is TSH testing?") So I have followed up with more information on how badly thyroid problems are treated by most doctors(including specialists) In order to make such a big claim, I need proof, which is provided below, with copious references. This is a long and fairly technical post, but those of you with thyroid problems or suspected thyroid issues, will be rewarded in wading through it. I suggest doing so in stages. (our brains can only absorb so much at one sitting – brain fog is one of the symptoms of under active thyroid)
From the National Academy of Hypothyroidism (www.nahypothyroidism.org)
Thyroid hormone transport is an extremely important topic. It must be clearly understood by any physician who hopes to accurately evaluate an individual's thyroid status and to appropriately treat thyroid dysfunction. Unfortunately, only a small fraction physicians and endocrinologists understand even the basics of thyroid transport, because what they have learned in medical school and continue to be taught regarding this topic is incorrect. When one understands the physiology involved with thyroid hormone transport, it becomes clear that standard blood tests, including the TSH and T4 levels, cannot be used to accurately determine intracellular and tissue thyroid level in the presence of a wide range of common conditions, including chronic and acute dieting, anxiety, stress, insulin resistance, obesity, diabetes, depression and bipolar disorder, hyperlipidemia (high cholesterol and triglycerides), chronic fatigue syndrome, fibromyalgia, neurodegenerative diseases (Alzheimer's, Parkinson's and multiple sclerosis), migraines, cardiomyopathy, and aging.
Serum thyroid levels are, of course, commonly used as an indication of cellular thyroid activity. In order to have biological activity, the T4 and T3 must, however, cross the cellular membrane from the serum into the target cells. It follows that the activity of these transport processes may have an important influence on the regulation of biological activity of the thyroid hormones. For about two and half decades it was assumed that the uptake of thyroid into the cells is by simple diffusion and that the driving force for this diffusion is the concentration of the free hormones in the serum. This "free hormone" or "diffusion hypothesis" was formulated in 1960 and assumes the concentration of free hormones (free T4 and free T3) in the serum determines the rate and extent of uptake into the cell and thus intracellular thyroid hormone concentration.
This hypothesis and mechanism of thyroid uptake into the cell has been shown to be totally incorrect (1-43). It has clearly been shown that the rate-limiting (most important) step in the determination of thyroid activity is the rate of thyroid hormone transport into the cell (5,20,41,44,45) and that this transport has nothing to do with diffusion, but rather it is energy requiring active transport (1-43,45,46,47,48-64,65,66,67). The incorrect "diffusion hypothesis," however, continues to be taught in medical school and is believed to be true by most physicians and endocrinologists (see thyroid transport graph).
Conditions associated with abnormal thyroid transport
It is important to note that because this transport of thyroid hormones into the cell is energy dependent, any condition associated with reduced production of the cellular energy (mitochondrial dysfunction) will also be associated with reduced transport of thyroid into the cell, resulting in cellular hypothyroidism despite having standard blood tests in the "normal" range. Conditions associated with reduced mitochondrial function and impaired thyroid transport include: insulin resistance, diabetes and obesity (68,69,70,71,106); chronic and acute dieting (4,51,66,72,112,113,114,115,116,117,118); diabetes (69,73,74,75,76); depression (73,77,78,79); anxiety (73,80); bipolar depression (73,77,81,82); neurodegenerative diseases (73,83,84,85,86,87); aging (73,74,88-100); chronic fatigue syndrome (73,101,102); fibromyalgia (73,103,104); migraines (73); chronic infections (73); physiologic stress and anxiety (73,79); cardiovascular disease (73,99,104,105,108); inflammation and chronic illness (73,109,110,111); and those with high cholesterol and triglyceride levels (58,60,72,106,107). Thus, standard blood tests can be very unreliable if any of these commonly occurring conditions are present (1-107).
The exact cause of the inhibition of the transport of thyroid is unknown, but it is clear that there are a number of substances that are produced by the body in response to dieting and physiologic stress that negatively effect thyroid hormone transport (5,41). This is clearly shown by studies where cell cultures are incubated with the serum from physiologically stressed or dieting individuals; there is shown to be a dramatic reduction of the uptake of T4 by the cells that correlates with the degree of stress (41,42).
Additionally, it has been clearly shown that there are different transporters that are specific and necessary for the transport of T4 and T3 into the cell where they have their effect. The transporter for T4 is much more energy dependent (it requires more energy) than the transporter for T3 (see figure 1) (5,40,41,49,52,53,66). Even slight reductions in cellular energy (mitochondrial function) results in dramatic declines in the uptake of T4 while the uptake of T3 is much less affected (5,41,62,67). Thus, the conditions listed above have, in particular, an impaired transport of T4 that results in cellular hypothyroidism. This cellular hypothyroidism is not detected by serum T4 levels because the less T4 transported into the cell and the lower the cellular level of T4, the higher the serum T4 level. The TSH will also not detect such cellular hypothyroidism because the pituitary has completely different transporters that are not energy dependent and increase transport activity, while the rest of body has impaired thyroid transport (see thyroid transport graph).
Pituitary thyroid transport determines TSH levels
As discussed previously, the pituitary is different than every cell in the body with different deiodinases and different high affinity thyroid receptors. It is also shown to have unique thyroid transporters that are different than those in the rest of the body (1,17,43,50,52,55,59,60,61). The pituitary thyroid hormone transporters are shown not to be energy dependent and will maintain or increase the uptake of T4 and T3 in low energy states, while this is not the case for transporters in other parts of the body that have significantly reduced transport (1,17,22,43,50,52,55,59,60,61).
The transporters for T4 and T3 in the pituitary are also not inhibited by numerous environmental toxins and substances produced by the body during physiologic stress and calorie reduction that inhibit thyroid transport into other cells in the body, including bilirubin and fatty acids. Thus, the reduced uptake of T3 and T4 and subsequent intracellular hypothyroidism that occurs throughout the body from numerous conditions stated above is not reflected by TSH testing because thyroid uptake in the pituitary cells is not effected, making the TSH a poor marker for cellular thyroid in any tissue other than the pituitary (1,43,55).
Even common medications, including benzodiazepines such as diazepam (Valium), lorazapam (Atavan) and alprazolam (Xanax), are shown to inhibit T3 uptake into the cells of the body but have no effect on transport of T3 into the pituitary (61).
This difference in pituitary thyroid transport was investigated by Germain et al. This study demonstrated that with calorie restriction (dieting), pituitary T3 content is independent of the rest of the body. The dramatically reduced serum T4 and T3 levels seen with dieting are associated with an increase in pituitary T3 receptor saturation (percent of activated T3 receptors), which results in a decrease in TSH even when serum levels were reduced by 50% (55).
Studies show that numerous conditions are associated with reduced transport of thyroid into the cells, which can lead to dramatic cellular hypothyroidism and symptoms that are not detected by standard blood tests because the TSH will be normal and serum T4 may actually increase due to reduced uptake into the cells (54). Most physicians and endocrinologist are unaware of the importance of the difference of this rate-limiting step in cellular thyroid activity in the pituitary and the rest of the body. Physicians are often quick to declare a person with numerous symptoms of low thyroid as having "normal" thyroid function based on a normal TSH and T4 level.
Wassen FS et al states in the Journal of Endocrinology that "These observations lend further support to the view that thyroid hormone transport into the pituitary is regulated differently than that in the liver (50)." As stated, the T4 level may be high normal. This high-normal T4 and low-normal TSH often leads an endocrinologist to erroneously make a diagnosis of "normal" or "high-normal" thyroid level while a patient is in fact suffering from low cellular thyroid levels (see thyroid transport graph).
Chronic emotional or physiologic stress can cause the significant reduction of T4 into the cells of the body while the pituitary is unaffected. A study published in the Journal of Clinical Endocrinology and Metabolism studied the effect of adding serum from different groups of individuals to cell cultures and measured the amount of T4 uptake from the serum into the cell. The study found that the serum from those with significant physiologic stress inhibited the uptake (transport) of T4 into the cell while the serum from non-physiological stress had no effect, demonstrating that serum T4 levels are artificially elevated in physiologically stressed individuals and that serum T4 and TSH levels are poor markers for tissue thyroid levels in stressed individuals (4).
A number of studies have shown that significant physiologic stress reduces cellular uptake T4 and T3 by up to 50% (63,64,109,110,111). Arem et al found that with significant physiological stress, tissue levels of T4 and T3 were dramatically reduced by up to 79% without an increase in TSH. Additionally, when comparing the T4 and T3 levels in different tissues in different individuals, there is significant variation. This large variation of T4 and T3 levels in different tissues (not reflected by TSH or serum T4 and T3 levels) explains the wide range of symptoms that are due to tissue specific hypothyroidism not reflected or detected by standard blood tests, including TSH and T4 (56).
A confirming study published in the Journal of Clinical Endocrinology and Metabolism also found that serum from non-stress individuals had no effect on T4 cellular uptake, while those with significant physiologic stress had up to a 44% reduction in T4 uptake into the cell (42). It was shown that the free T3/reverse T3 ratio was the most accurate marker for reduced cellular uptake of T4 (42).
A number of substances have been identified that are produced in response to physiologic stress or calorie reduction. These include 3-carboxy-4-methyl-5-propyl-2-furna propanoic acid (CMPF), indoxyl sulfate, billirubin and fatty acids (1,3,57,58,60). The addition of these substances to cell cultures in concentrations comparable to those seen in patients results in a 27%-42% reduction in cellular uptake of T4 but has no effect on T4 or T3 uptake into the pituitary (1,17,57,58,60) (see thyroid transport graph).
In a highly controlled study, Brownell et al found that after repeated cycles of dieting, weight loss occurred at half the rate and weight gain occurred at three times the rate compared to controls with the same calorie intake (118). Chronic and yo-yo dieting, frequently done by a large percentage of the population, is shown to be associated with reduced cellular T4 uptake of 25%-50% (3,49,112,114,115,116). Successful weight loss is doomed to failure unless the reduced intracellular thyroid levels are addressed, but this reduced cellular thyroid level is generally not detected by standard laboratory testing unless a free T3/reverse T3 ratio is done.
In a study published in the American Journal of Physiology-Endocrinology and Metabolism, Van der Heyden et al studied the effect of calorie restriction (dieting) on the transport of T4 and T3 into the cell (49). It was found that dieting obese individuals had a 50% reduction of T4 into the cell and a 25% reduction of T3 into the cell due to the reduced cellular energy stores, demonstrating that in such patients standard thyroid blood tests are not accurate indicators of intracellular thyroid levels. This also demonstrates why it is very difficult for obese patients to lose weight; as calories are decreased, thyroid utilization is reduced and metabolism drops. This will, however, not be detected by standard TSH, T4 and T3 testing (a free T3/reverse T3 can aid in the diagnosis of reduced uptake of thyroid hormones and intracellular hypothyroidism). Additionally, there are increased levels of free fatty acids in the serum with chronic dieting, which further suppresses T4 uptake into the cells and further cellular hypothyroidism (106,72,57,58,114).
Many overweight individuals fail to lose weight with dieting. While it is always assumed they are doing a poor job of dieting, it has been shown, however, that chronic dieting in overweight individuals results in increased levels of NEFA, which suppresses T4 uptake into the cells (3). This suppressed T4 uptake results in reduced intracellular T4 levels and subsequent T4 to T3 conversion and a reduced metabolism (3,112,114,115,116) (see thyroid transport graph).
TSH and serum T4 levels fail to correlate with intracellular thyroid levels. Additionally, the free T3 will also tend to be less accurate with reduced cellular energy. This artificial elevation of T3 due to be reduced uptake into the cell is generally offset by a reduced T4 to T3 conversion due to reduced uptake and T4 and subsequent conversion to T3, making T3 a more accurate marker than the TSH or T4 with physiologic stress. Also, the transporter for reverse T3 (rT3) is similar to T4 in that it is energy dependent and has the same kinetics as the T4 transporter (6,41,45,62,66,67). This property (among others) makes it the most useful indicator of diminished transport of T4 into the cell (45).
Thus, a high reverse T3 demonstrates that there is either an inhibition of reverse T3 uptake into the cell and/or there is increased T4 to reverse T3 formation. These always occur together in a wide range of physiologic conditions and both cause reduced intracellular T4 and T3 levels and cellular hypothyroidism. Thus, reverse T3 is an excellent marker for reduced cellular T4 and T3 levels not detected by TSH or serum T4 and T3 levels. Because increased rT3 is a marker for reduced uptake of T4 and reduced T4 to T3 conversion, any increase (high or high normal) in rT3 is not only an indicator of tissue hypothyroidism but also that T4 only replacement would not be considered optimal in such cases and would be expected to have inadequate or sub-optimal results. A high reverse T3 can be associated with hyperthyroidism as the body tries to reduce cellular thyroid levels, but this can be differentiated by symptoms and by utilizing the free T3/reverse T3 ratio, which is proving to be the best physiologic marker of intracellular thyroid levels (see Diagnosis of low thyroid due to stress & illness Graph).
Levothyroxine (T4)-only replacement with products such as Synthroid and Levoxyl are the most widely accepted forms of thyroid replacement. This is based on a widely held assumption that the body will convert what it needs to the biologically active form T3. Based on this assumption, most physicians and endocrinologists believe that the normalization of TSH with a T4 preparation demonstrates adequate tissue levels of thyroid. This assumption, however, had never been directly tested until two studies were published (119,120). The first study investigated whether or not giving T4 only preparations will provide adequate T3 levels in varying tissues. Plasma TSH, T4 and T3 levels and 10 different tissue levels of T4 and T3 were measured after the infusion of 12-13 days of thyroxine.
This study demonstrated that the normalization of plasma TSH and T4 levels with T4-only preparations provide adequate tissue T3 levels to only a few tissues, including the pituitary (hence the normal TSH), but almost every other tissue will be deficient. This study demonstrated that it is impossible to achieve normal tissue levels of T3 by giving T4 only preparations unless supra-physiological levels of T4 are given. The authors conclude: "It is evident that neither plasma T4 nor plasma T3 alone permit the prediction of the degree of change in T4 and T3 concentrations in tissues…the current replacement therapy of hypothyroidism [giving T4] should no longer be considered adequate…(119)."
The second study compared the plasma TSH, T4 and T3 levels and 13 different tissue levels of T4 and T3 when T4 or T4/T3 preparations were utilized (120). This study found that a combination of T4/T3 is required to normalize tissue levels of T3. The study found that the pituitary was able to maintain normal levels of T3 despite the rest of the body being hypothyroid on T4 only preparations. Under normal conditions it was shown that the pituitary will have 7 to 60 times the concentration of T3 of other tissues of the body; and when thyroid levels drop, the pituitary was shown to have 40 to 650 times the concentration of T3 of other tissues. Thus, the pituitary is unique in its ability to concentrate T3 in the presence of diminished thyroid levels that are not present in other tissues. Consequently, the pituitary levels of T3 and the subsequent level of TSH are poor measures of tissue hypothyroidism, as almost the entire body can be severely hypothyroid despite having a normal TSH level (120).
These studies add to the large amount of medical literature demonstrating that pituitary thyroid levels are not indicative of other tissues in the body and showing why the TSH level is a poor indicator of a proper thyroid dose. These studies also demonstrate that it is impossible to achieve normal tissue thyroid levels with T4 preparations such as Synthroid and Levoxyl. It is no surprise that the majority of patients on T4 preparations will continue to suffer from symptoms of hypothyroidism despite being told their levels are "normal." Patients on T4 only preparations should seek out a physician who is well-versed in the medical literature and understands the physiologic limitations and inadequacy of commonly used thyroid preparations.
The dramatic reduction of T4 cellular uptake with a wide variety of conditions (T3 being less affected) also explains why T4 preparations are often associated with poor clinical response and continued residual symptoms that the unknowing physician assumes is not due to low thyroid, because serum levels look "good" if the physician does not understand the potential effects of reduced thyroid hormone transport. As stated by Hennemann G et al in Endocrine Reviews: "Even a small decrease in cellular ATP concentration results in a major reduction in the transport of T4 (and rT3) but only slightly affects T3 uptake (5)." This makes it inappropriate to use T4-only preparations if treating any condition associated with the following: reduced mitochondrial function or ATP production, which includes insulin resistance, diabetes and obesity 68,69,70,71,106); chronic and acute dieting (4,51,66,72,112,113,114,115,116,117,118); diabetes (69,73,74,75,76); depression (73,77,78,79); anxiety (73,80); bipolar depression (73,77,81,82); neurodegenerative diseases (73,83,84,85,86,87); aging (73,74,88-100); chronic fatigue syndrome (73,101,102); fibromyalgia (73,103,104); migraines (73); chronic infections (73); physiologic stress and anxiety (73,79); cardiovascular disease (73,99,104,105,108) and inflammation and chronic illness (73,109,110,111); Likewise, high cholesterol, fatty acids or triglyceride levels also selectively inhibit T4 transport into the cell as opposed to T3 (57,58,60,72,106,107,114), making T4-only preparations physiologically inappropriate for individuals with high cholesterol or triglycerides or who are chronic dieters, which dramatically increases serum free fatty acids (72). It is not surprising that T3 has been shown to be superior in such patient populations.
Fraser et al investigated the correlation between tissue thyroid activity and serum blood tests (TSH, free T4 and T3) and published their results in the British Medical Journal. The study authors concluded that "The serum concentration of thyroid stimulation hormone is unsatisfactory as the thyrotrophs in the anterior pituitary are more sensitive to changes in the concentration of thyroxin in the circulation than other tissues, which rely more on triiodothyronine (T3)." They found a suppressed or undetectable TSH was not an indication or a reliable marker of over replacement or hyperthyroidism. They state,
"It is clear that serum thyroid hormone and thyroid stimulating hormone concentrations cannot be used with any degree of confidence to classify patients as receiving satisfactory, insufficient, or excessive amounts of thyroxine replacement…The poor diagnostic sensitivity and high false positive rates associated with such measurements render them virtually useless in clinical practice…Further adjustments to the dose should be made according to the patient's clinical response." (121)
The positive predictive value of the TSH, which is the likelihood that as suppressed TSH indicates over replacement or hyperthyroidism, was determined to be 16%. In other words, a suppressed TSH is not associated with hyperthyroidism or over-replacement 84% of the time, making it an inaccurate and inappropriate marker to determine appropriate replacement dosing. Additionally, the TSH becomes an even worse indicator the optimal replacement dose in the following situations: if a person has insulin resistance or obesity (68,69,70,71,106); is a chronic dieter (4,51,66,72,112,113,114,115,116,117,118); has diabetes (69,73,74,75,76); has depression (73,77,78,79); has bipolar depression (73,77,81,82); has a neurodegenerative diseases (73,83,84,85,86,87); is of older age (73,74,88-100); has chronic fatigue syndrome (73,101,102); has fibromyalgia (73,103,104); migraines (73); has a chronic infections (MT63)(73); is stressed or anxious (73,79,80); has heart failure or cardiovascular disease (73,99,104,105,108); suffers from migraines (73); has inflammation or a chronic illness (73,109,110,111); or has high cholesterol or triglyceride levels (57,58,60,72,106,107,114).
In a study published in the British Medical Journal, Meir et al also investigated the correlation of TSH and tissue thyroid effect. It was shown that the TSH level had no correlation with tissue thyroid levels and could not be used to determine a proper or optimal thyroid replacement dose. The authors concluded that "TSH is a poor measure for estimating the clinical and metabolic severity of primary overt thyroid failure. … We found no correlations between the different parameters of target tissues and serum TSH." They stated that signs and symptoms of thyroid effect and not the TSH should be used to determine the proper replacement dose (122).
Alevizaki et al also studied the accuracy of using the TSH to determine the proper thyroid replacement dose in T4 treated individuals. The study found that such a practice of using the TSH, although common, results in the majority of tissues being hypothyroid, except for the pituitary. They conclude, "TSH levels used to monitor substitution, mostly regulated by intracellular T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone action in all tissues (123)."
In a study published in the Journal of Clinical Endocrinology and Metabolism, Zulewski et al also investigated the accuracy of TSH to determine proper thyroid replacement. The study found that the TSH was not a useful measure of optimal or proper thyroid replacement, as there was no correlation between the TSH and tissue thyroid levels. Serum T4 and T3 levels had some correlation, with T3 being a better indictor than T4. In contrast, a clinical score that involved a thorough assessment of signs and symptoms of hypothyroidism was shown to be the most accurate method to determine proper replacement dosing. The authors also agreed that it is improper to use the TSH as the major determinant of the proper or optimal doses of thyroid replacement, stating "The ultimate test of whether a patient is experiencing the effects of too much or too little thyroid hormone is not the measurement of hormone concentration in the blood but the effect of thyroid hormones on the peripheral tissues [symptoms] (124)."
The most important determinant of thyroid activity is the intra-cellular level of T3, and the most important determinant of the intracellular T3 level is the activity of the cellular thyroid transporters (1-67). Reduced thyroid transport into the cell is seen with a wide range of common conditions, including insulin resistance, diabetes, depression, bipolar disorder, hyperlipidemia (high cholesterol and triglycerides), chronic fatigue syndrome, fibromyalgia, neurodegenerative diseases (Alzheimer's, Parkinson's and multiple sclerosis), migraines, stress, anxiety, chronic dieting and aging (1-43,46,49,51,52,53,58,60,66,68,69,72-118).
This high incidence of reduced cellular thyroid transport seen with these conditions makes standard thyroid tests a poor indicator of cellular thyroid levels in the presence of such conditions. The pituitary has different transporters than every other tissue in the body; the thyroid transporters in the body are very energy dependent and affected by numerous conditions while the pituitary is minimally affected. Because the pituitary remains unaffected, there is no elevation in TSH despite wide-spread tissue hypothyroidism, making the TSH an inaccurate marker for tissue T3 levels under the numerous conditions listed above (1,3,4,17,22,43,50,52,55,59,60,61).
The reduced thyroid transport seen with these conditions results in an artificial elevation in serum thyroid levels (especially T4), making this a poor marker for tissue thyroid levels as well (5,40,41,49,52,53,62,66,67). An elevated or high-normal reverse T3 is shown to currently be the best marker for reduced transport of thyroid hormones and an indication that a person has low cellular thyroid levels despite the fact that standard thyroid tests such as TSH, free T4, and free T3 are normal (6,32,41,45,62,66,67,125-172) (see Diagnosis of low thyroid due to stress & illness Graph).
The intracellular T3 deficiency seen with these conditions often results in a vicious cycle of worsening symptoms that usually goes untreated because standard thyroid tests look normal. Additionally, it is not surprising that T4 preparations are generally ineffective in the presence of such conditions, while T3 replacement is shown to be beneficial, with potentially dramatic results (71,74,75,76,80,81,82,86,97,98,99,100,101,102,103,104,105,173-198). In the presence of such conditions, it should be understood that significant intracellular hypothyroidism may exist that remains undiagnosed by standard blood tests (the freeT3/reverse T3 ratio may aid in the diagnosis). Thus, more appropriated testing beyond standard thyroid function tests should be considered and supplementation with T3 should be considered with such patients.
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Keep calm – it's the secret to ageing well
December 9, 2015 1.42am AEDT
Nicholas Robert Cooper, Amanda Claire Marshall, and Nicolas Geeraert
Nicholas Robert Cooper
Academic Director of the Centre for Brain Science, University of Essex
Amanda Claire Marshall
PhD Researcher, University of Essex
Nicolas Geeraert
The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond the academic appointment above.
University of Essex provides funding as a member of The Conversation UK.
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Get your chill on. www.shutterstock.com
As we get older our physical and mental abilities decline, but it doesn't have to be that way. Research suggests that the way we live our lives – our diets, our exercise regimes – can have a big impact on how we age. And it's not just about the things we do to age well, it's also about the things we avoid.
There is a large field of research that seeks to understand the factors that cause different rates of age-related decline. In particular, scientists look at how these factors change our ability to remember and pay attention to things in everyday life. We call such changes "cognitive ageing".
Earlier work has looked at how diet or doing physical or mental exercise (sudoku, crosswords) affects ageing. However, the amount of stress we experience over a lifetime and the impact it has on cognitive ageing has remained an under-researched area, until recently.
A lifetime of stress
Work from our lab and from others has found that many of the negative aspects of cognitive ageing seen in older people appear to be linked to the amount of stress they have experienced in their life. We began by measuring the number of stressful events experienced over the lifetime. We looked at a number of factors ranging from experiencing a major illness or losing a loved one, to changing one's social habits or moving home. Old people who have experienced a lot of stress tend to perform worse on cognitive tasks than those who experienced less stress.
Crucially, old people who haven't experienced much stress in their life perform just as well on cognitive tasks as young people. This suggests that stress has a big impact on mental ability and that the effect of this only appears in old age. Indeed, young people did not differ from each other in their performance of cognitive tests whatever their life experience of stress had been.
Not only that but the patterns of brain activity of the people taking part in our study reflect the same effect: older people (aged 60 to 80) who have experienced less stress have brain activity similar to that of younger people. However, when it comes to the brain activity of those elderly people who have led stressful lives, we find something very different going on.
EEG reveals different patterns of brain activity www.shutterstock.com
This brain activity may give us some clues as to what's going wrong and where in the brain it is happening. For instance, depending on the task involved, we can see that a significant amount of stress in a person's lifetime can affect their ability to hold items in their short-term memory and can also reduce their ability to stop irrelevant thoughts from interfering with this process.
In particular, stress appears to affect an area of the brain essential for the formation of new memories (the hippocampus).
But the long-term effects of stress are not only apparent in memory: recently it has been shown for the first time that brain processes and behaviour associated with our control of attention and movement are also impaired. This may relate to brain activity you use trying to stop a physical movement (such as moving your arm) that you have already initiated or activity linked to controlling where your attention is focused.
Do something about it
So what can we do about it? Most of us know when we are feeling stressed. For those of us who don't, smart devices can be used to alert us to the presence of potential dangers. By being aware of stress and its long-term consequences, we can begin to tackle it and to find ways to lessen its consequences.
The paths to de-stressing are numerous. Some people find meditation and mindfulness to be useful, for others the same techniques could be fruitless or even dangerous. Each person needs to find what works for them. It may take a bit of experimenting, but the pay-off will be worth it. Just don't expect it to do anything for your wrinkles.
How the 'Dirt Cure' Can Make for Healthier Families
I have been concerned for some time by the amount of allergies and allergic/autoimmune diseases in society at present – far more than existed in the past. In African and India, there is far less of these disorders. We are becoming too clean for our own good. See the article below, which expresses my sentiments exactly.
By Anahad O'Connor
Dr. Maya Shetreat-Klein has a message for the parents of small children: Don't be afraid of dirt.
She is a firm believer in the idea that children in Westernized countries today grow up in a world that can be too sanitized. They spend less time outdoors exploring nature and more time in front of screens than they did two decades ago. They eat foods that are heavily processed. Many do not know what it's like to taste fresh, seasonally grown foods plucked from a garden with nutrient-rich soil.
Dr. Shetreat-Klein, a pediatric neurologist in New York and an instructor at New York Medical College, explores these themes in a new book, "The Dirt Cure: Growing Healthy Kids With Food Straight from Soil." The book delves into research that suggests that spending time around farms, parks and other green spaces can benefit children in surprising ways, protecting against allergies, enhancing immune function and potentially even improving attention span and academic performance.
Dr. Shetreat-Klein wrote the book after a frightening experience with her youngest son, who started wheezing, breaking out in rashes and showing signs of delayed cognitive development after his first birthday. Various doctors suggested it was nothing to worry about.
But Dr. Shetreat-Klein eventually went to see an allergist who determined that her son was severely allergic to soy. Weaning him off of soy, which is added to many processed foods, proved difficult at first. But a week after eliminating soy from her son's diet, Dr. Shetreat-Klein noticed that his problems began to dissipate.
She and her family then set out on a journey to reconnect with nature. Despite living in the Bronx, one of the most densely populated, urban counties in the country, they started growing their own food, taking trips to farmers' markets and going on nature hikes. They even raise their own chickens.
Recently we caught up with Dr. Shetreat-Klein to talk about her book, why she feels so strongly about exposing children to "good old-fashioned dirt," and what families who live in urban areas can do to get closer to nature. Here are edited excerpts from our conversation.
You've said that your son's allergy was part of the impetus for this book. How so?
It was the beginning of my investigation into how food impacts children's health, why children are so allergic today, and how this impacts their cognition, development and behavior. I learned for one thing that food has changed dramatically in the last 20 years – from the way it is grown literally from seed to sprout to plate, how it's processed, and the kinds of additives that are used. Children's environments have changed, and so have the foods they're eating.
Explain what you mean by "dirt cure" in the title of your book.
Dirt means three things to me. It's eating nutrient-dense food from healthy soil. It's being exposed to certain microbes. And it's spending time outdoors in nature.
Why is it that children who grow up on farms tend to have lower rates of asthma and other allergies?
We used to think that children who grew up on farms were healthier than children in urban environments because they were exposed to more microbes. But studies have found that the number of bacteria in urban environments and on farms is similar. The difference is the diversity of the bacteria. Microbial diversity seems to have a very powerful impact. Children's immune systems are very social: They like to meet and greet a lot of things. It seems the more they meet and greet, the more likely they are to be in balance, and the less likely they are to let any one microorganism grow out of control, as occurs with infection.
What is the microbial diversity like in soil?
In one teaspoon of soil there are more organisms than there are humans on our planet. Soil houses about 25 percent of the world's biodiversity. What we also know from studies is that when children spend time in green environments – in natural playgrounds, for example, or in parks and forests – they perform better on standardized tests, they're more creative, they're happier and their cortisol levels are lower, so they're calmer and less stressed. And I think that might be somewhat related to the kind of organisms they're exposed to when they're playing outdoors.
Can you talk about how microbial diversity in soil relates to food?
The organisms in soil have an impact on the health of our food. Part of what makes fruits and vegetables good for us is the phytonutrients in them – the things that make cranberries red or coffee bitter. Phytonutrients are part of the plant's immune systems. Organisms in the soil that we might think of as pests actually stimulate plants to make more phytonutrients. So these small stressors actually in a sense enhance our health. Being exposed to different organisms improves the health of the plant and it improves our health as well.
Based on your research, what are some things you would like to see change?
I think we need more outdoor and nature-based curriculum in schools because this actually benefits children from a health perspective and a learning perspective. Children are more focused and they perform better on tests after they've spent time outside in nature. In Japan there's this idea called "Shinrin-yoku," or forest bathing, which means taking short visits to the forest. It's been shown to reduce inflammatory markers in the body and boost beneficial hormones. We know there are many physical benefits to children being outdoors and being physically active in nature
As someone who lives in New York City, how do you manage to spend time in nature?
We live in the Bronx, and although a lot of people may not realize it, the Bronx actually has a tremendous amount of parkland. We go to Van Cortlandt Park as well as the Bronx Zoo and the New York Botanical Garden, which are all very close by. We live by Riverdale Park, which is a beautiful little forest. We visit Bear Mountain and Rockefeller State Park and go on beautiful hikes. And we go to Central Park. It's actually not that difficult to get to a lot of these places for a day trip.
How do you incorporate the food philosophy you've talked about into your life?
When I was initially going through this journey, I lived in an apartment. But I found an office in the Bronx that had an empty lot out back and I decided to start a garden there. The soil was like dust, so we had to enrich it. And we planted a food forest. There were fruit trees. I grew cold-hardy kiwis, beans, melons, berries and then vegetables. We ate fresh produce that we grew in the garden. And I decided to keep chickens.
Do you still maintain it?
Now I live in a house with a little yard so I keep the chickens in my garden and we grow vegetables there. I like to know where my food is coming from. I want to eat eggs from chickens that are scratching outside and exposed to the sun and nibbling on greens. So I did those things and although it was difficult, it wasn't nearly as difficult as I thought it would be. It was far more accessible than most people would imagine. We also shop at farmers' markets once or twice a week to stock up and add to what we're growing.
How does your family get involved?
I have three kids and they love it. It's a family affair. They help me plant. They help me weed. They run outside when I'm cooking dinner to harvest celery, parsley or tomatoes. Sometimes in the morning they run outside to see if the chickens have laid eggs. My husband helps too. He appointed himself keeper of the chickens.
What are some recommendations for people who live in very urban environments?
Take a trip to the forest with your family. It may be difficult during the week, but maybe you can do it on the weekends. That's another reason why we should also be valuing green spaces in cities. Community gardens are also wonderful. So are farmers' markets. They expose children to fresh foods, which taste completely different. And it also exposes them to potentially healthy microbes through the traces of soil that might be left over on the fruits and vegetables when you buy them at a farmers' market.
How Accurate is TSH Testing?
It is becoming increasingly clear to me that patients have under-active thyroids that are being missed by their doctors. The standard thyroid test is inadequate for the task. See the article below. proper functioning of our thyroid glands is essential for good health, and the evidence is that the thyroid gland starts to decline with age. People should insist on the full range of thyroid tests, even if it means paying for it, as medicare wont foot the bill for the full cost. This post below is from the National Academy of Hypothyroidism. (www.nahypothyroidism.org)
Diagnosis of Hypothyroidism:
Are we getting what we want from TSH testing?
Hypothyroidism is a common disorder where there is inadequate cellular thyroid effect to meet the needs of the tissues. Typical symptoms of hypothyroidism include fatigue, weight gain, depression, cold extremities, muscle aches, headaches, decreased libido, weakness, cold intolerance, water retention, premenstrual syndrome (PMS) and dry skin. Low thyroid causes or contributes to the symptoms of many conditions but the deficiency is often missed by standard thyroid testing. This is frequently the case with depression, hypercholesterolemia (high cholesterol), menstrual irregularities, infertility, PMS, chronic fatigue syndrome (CFS), fibromyalgia, fibrocystic breasts, polycystic ovary syndrome (PCOS), hyperhomocysteinuria (high homocystine), atherosclerosis, hypertension, obesity, diabetes and insulin resistance.
The TSH is thought to be the most sensitive marker of peripheral tissue levels of thyroid, and it is erroneously assumed by most endocrinologists and other physicians that, except for unique situations, a normal TSH is a clear indication that the person's tissue thyroid levels are adequate (symptoms are not due to low thyroid) (see why doesn't my doctor know this). A more thorough understanding of the physiology of hypothalamic-pituitary-thyroid axis and tissue regulation of thyroid hormones demonstrates that the widely held belief that the TSH is an accurate marker of the body's overall thyroid status is clearly erroneous.
The TSH is inversely correlated with pituitary T3 levels but with physiologic stress (1-32), depression (33-38), insulin resistance and diabetes (28,39,116,117), aging (30,40-49), calorie deprivation (dieting)(27, 50-57), inflammation (5-8,22,108,109-111), PMS (58,59), chronic fatigue syndrome and fibromyalgia (60,61), obesity (112,113,114) and numerous other conditions (1-32), increasing pituitary T3 levels are often associated with diminished cellular and tissue T3 levels and increased reverse T3 levels in the rest of the body (1-62) (see pituitary diagram). The pituitary is both anatomically and physiologically unique, reacting differently to inflammation and physiologic stress than every other tissue in the body (1-20,50-52,62,63)(see deiodinase). The conditions above stimulate local mechanisms to increase pituitary T3 levels (reducing TSH levels) while reducing T3 levels in the rest of the body (1-63). Thus, with physiologic or emotional stress, depression or inflammation, the pituitary T3 levels do not correlate with T3 levels in the rest of the body, and thus, the TSH is not a reliable or sensitive marker of an individual's true thyroid status (see deiodinase).
Serum levels of thyroid hormones
(see serum thyroid hormones graph)
Due to the differences in the pituitary's response to physiological stress, depression, dieting, aging and inflammation as discussed, most individuals with diminished tissue levels of thyroid will have a normal TSH (1-63). Doctors are taught that if active thyroid (T3) levels drop, the TSH will increase. Thus, endocrinologists and other doctors tell patients that an elevated TSH is the most useful marker for diminished T3 levels and that a normal TSH indicates that their thyroid status is "fine". The TSH is, however, merely a marker of pituitary levels of T3 and not of T3 levels in any other part of the body. Only under ideal conditions of total health do pituitary T3 levels correlate with T3 levels in the rest of the body, making the TSH a poor indicator of the body's overall thyroid status. The relationship between TSH and tissue T3 is lost in the presence of physiologic or emotional stress (1-32), depression (33-38), insulin resistance and diabetes (28,39), aging (30,40-49)(see thyroid hormones and aging graph), calorie deprivation (dieting)(50-57), inflammation (5-8,22), PMS (58,59), chronic fatigue syndrome and fibromyalgia (60,61), obesity (112,113,114) and numerous other conditions (1-63). In the presence of such conditions, the TSH is a poor marker of active thyroid levels and thyroid status of an individual, and a normal TSH cannot be used as a reliable indictor that a person is euthyroid (normal thyroid) in the overwhelming majority of patients.
Value of Serum T4
The suppression of TSH with physiologic and emotional stress and illness suppresses the production of T4 (1,2,9,64-68), which would tend to lower serum T4 levels. In the presence of such conditions, there are, however, competing effects that result in an increase in serum T4 while further reducing tissue levels of T3 levels, making serum T4 (or free T4) a poor marker of tissue thyroid level, as is the case with the TSH. Such effects include a suppression of tissue T4 to T3 conversion (misleadingly increasing serum T4 levels) (1-68,76) with an increased conversion of T4 to reverse T3 (12,14,18,35,36,41,59,69-74,85) and an induced thyroid resistance with reduced uptake of T4 into the cells (misleadingly increasing serum T4 levels) (16,1976-84) in all tissues except for the pituitary (84). Although all such effects reduced intracellular T3 in all tissues except for the pituitary, the serum T4 level can be increased, decreased or unchanged. Consequently, serum T4 levels oftentimes do not correlate with tissue T3 levels and, as with the TSH, the serum T4 level is often misleading and an unreliable marker of the body's overall thyroid status (see serum thyroid levels in stress and illness).
Current best method to diagnosis
With increasing knowledge of the complexities of thyroid function at the cellular level, it is becoming increasingly clear that TSH and T4 levels are not the reliable markers of tissue thyroid levels as once thought, especially with chronic physiologic or emotional stress, illness, inflammation, depression and aging. It is common for an individual to complain of symptoms consistent with hypothyroidism but have normal TSH and T4 levels. While there are limitations to all testing and there is no perfect test, obtaining free triiodothyronine, reverse triiodothyronine, and triiodothyronine/reverse-triiodothyronine ratios can be helpful to obtain a more accurate evaluation of tissue thyroid status and may be useful to predict those who may respond favorably to thyroid supplementation (1,11,12,14,18,35,36,41,59,69-74,85) (see serum thyroid levels in stress and illness). Many symptomatic patients with low tissue levels of active thyroid hormone but normal TSH and T4 levels significantly benefit from thyroid replacement, often with significant improvement in fatigue, depression, diabetes, weight gain, PMS, fibromyalgia and numerous other chronic conditions (86-99).
With an understanding of thyroid physiology, it becomes clear why a large percentage of patients treated with T4 only preparations continue to be symptomatic. Thyroxine (T4) only preparations should not be considered the treatment of choice and are often not effective in conditions associated with reduced T4 to T3 conversion, reduced uptake of T4 or increased T4 to reverse T3 conversion. As discussed above, with any physiologic stress (emotional or physical), inflammation, depression, inflammation, aging or dieting, T4 to T3 conversion is reduced and T4 will be preferentially converted to reverse T3 (12,14,18,35,36,41,53,69-74,85), which acts a competitive inhibitor of T3 (blocks T3 at the receptor) (100-104), reduces metabolism (100,103,104), suppresses T4 to T3 conversion (101,103) and blocks T4 and T3 uptake into the cell (105).
While a normal TSH cannot be used as a reliable indicator of global tissue thyroid effect, even a minimally elevated TSH (above 2) demonstrates that there is diminished intra-pituitary T3 level and is a clear indication (except in unique situations such as a TSH secreting tumor) that the rest of the body is suffering from inadequate thyroid activity because the pituitary T3 level is always significantly higher than the rest of the body and the most rigorously screened individuals for absence of thyroid disease have a TSH below 2 to 2.5 (106). Thus, treatment should likely be initiated in any symptomatic person with a TSH greater than 2. Additionally, many individuals will secrete a less bioactive TSH so for the same TSH level, a large percentage of individuals will have reduced stimulation of thyroid activity, further limiting the accuracy of TSH as a measure of overall thyroid status. Reduced bioactivity of TSH is not detected by current TSH assays used in clinical practice.
Due to the lack of correlation of TSH and tissue thyroid levels, as discussed, a normal TSH should not be used as the sole reason to withhold treatment in a symptomatic patient. A symptomatic patient with an above average reverse T3 level and a below average free T3 (a general guideline being a free T3/reverse T3 ratio less than 2) should also be considered a candidate for thyroid supplementation (13,14,18,69-76,85-106). A relatively low sex hormone binding globulin (SHBG) and slow reflex time can also be useful markers for low tissue thyroid and levels and can aid in the diagnosis of tissue hypothyroidism (93,107,115).
A study published in the Journal of Clinical Endocrinology and Metabolism assessed the level of hypothyroidism in 332 female patients based on a clinical score of 14 common signs and symptoms of hypothyroidism and assessments of peripheral thyroid action (tissue thyroid effect). The study found that the clinical score and ankle reflex time correlated well with tissue thyroid effect but the TSH had no correlation with the tissue effect of thyroid hormones (118). The ankle reflex itself had a specificity of 93% (93% of those with slow relaxation phase of the reflexes had tissue hypothyroidism) and a sensitivity of 77% (77% of those with tissue hypothyroidism had a slow relaxation phase of the reflexes) making both the measurement of the reflex speed and clinical assessment a more accurate measurement of tissue thyroid effect than the TSH.
A combination of the serum levels of TSH, free T3, free T4, reverse T3, anti-TPO antibody, antithyroglobulin antibody and SHBG should be used in combination of with clinical assessment and measurement of reflex speed and basal metabolic rate to most accurately determine the overall thyroid status in a patient. Forgoing treatment based on a normal TSH without further assessment will result in the misdiagnosis of mismanagement of a large number of hypothyroid patients that may greatly benefit with treatment. Simply relying a TSH to determine the thyroid status of a patient demonstrates a lack of understanding of thyroid physiology and is not evidence based medicine (see Why my Endocrinologist Doesn't Know All of This). In patients with elevated or high normal reverse T3 levels, T4 only preparations should not be considered adequate and T3 containing preparations, in particular timed released T3, should be considered the treatment of choice.
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86. Lowe J, Garrison R, Reichman A, MD, Yellin J, Thompson BA, Kaufman D. Effectiveness and safety of T3 (triiodothyronine) therapy for euthyroid fibromyalgia: a double-blind placebo-controlled response-driven crossover study.: Clinical Bulletin of Myofascial Therapy, 2(2/3):31-58, 1997.
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96. Abraham G, Milev R, Lawson JS. T3 augmentation of SSRI resistant depression. Journal of Affective Disorders 2006;91:211–215
97. Posternak M, Novak S, Stern R, Hennessey J, Joffe R, et al. A pilot effectiveness study: placebo-controlled trial of adjunctive L-triiodothyronine (T3) used to accelerate and potentiate the antidepressant response. International Journal of Neuropsychopharmacology (2008), 11, 15–25.
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Low Thyroid Equals Low Libido
Posted on February 11, 2016 by Naomi Parker
Valentine's Day is right around the corner and love is in the air! For those of you that need a reminder: Valentine's Day is Sunday! With the holiday of love being just a few days away many are thinking of things they can do for their significant other, or with their significant other, if you know what I mean. While Valentine's Day may seem like the perfect day for it, many people suffer from low libido (sex drive) and their thyroid may be to blame!
True, we blame the thyroid for a lot of things, but that's because it is closely involved in so many functions of the body and the sex drive is no different. It's important to address that many people believe that low sex drive just comes with age, especially for women. That may be true, but there is an underlying reason: as you age your hormones can become imbalanced. Think about all those women going through menopause! It is no different for those with a thyroid problem; their hormones are becoming imbalanced, too. To be clear, this is more common in individuals with HYPOthyroidism, but can still be a symptom in those with HYPERthyroidism.
Here's how it works. The thyroid is in control of the metabolism and with hypothyroidism, the metabolism is slowed down. This causes other organs and glands to slow down as well, like the reproductive organs and the adrenal glands which produce hormones that convert into sex hormones (testosterone, estrogen, and progesterone). Low levels of these hormones result in a low sex drive and both genders can be affected.
If this is something you are experiencing yet you don't feel comfortable addressing these issues with your doctor, don't worry, you are not alone! A study in the Journal of the American Medical Associated (JAMA) published in February of 1990 stated that out of a sample of 1749 women and 1410 men aged between 18 and 59 years if age, 43% of women and 31% of men suffer from sexual dysfunction.
Ian L. Goldman, M.D., director of the Marshfield Clinic Center for Sexual Health states that according to a recent survey more than 70% of patients said they would be hesitant to discuss sex with their doctor.
In addition to the hormonal imbalances caused by thyroid dysfunction, lack of sex drive can also be attributed to the fatigue associated with hypothyroidism. Let's face it, when we suffer from severe fatigue we don't want to go to work and do the things we have to do, let alone something that is optional.
This Valentine's Day do yourself and your significant other a favor and get your thyroid checked. Have a full thyroid panel ran which should include free T4, free T3, reverse T3, TSH, anti-TPO antibody, and antithyroglobulin antibody. Also, since your sex drive is suffering, it would be a great idea to include your sex hormones, testosterone, progesterone, and estrogen. Once you receive your results, talk to your doctor about your options and make sure you are getting the best treatment possible!
Laumann E, et. al. "Sexual dysfunction in the United States: prevalence and predictors." JAMA. 1999 Feb 10;281(6):537-44
Testosterone replacement therapy in the aging male‏.
This statement was put out by the European Menopause and Andropause Society. The best brains in this area have forwarded their considered opinion on the benefits or not of using testosterone in aging men. It appears to be very positive.
Maturitas. 2015 Nov 10. pii: S0378-5122(15)00808-7. doi: 10.1016/j.maturitas.2015.11.003. [Epub ahead of print]
EMAS position statement: Testosterone replacement therapy in the aging male‏.
Dimopoulou C1, Ceausu I2, Depypere H3, Lambrinoudaki I4, Mueck A5, Pérez-López FR6, Rees M7, van der Schouw YT8, Senturk LM9, Simonsini T10, Stevenson JC11, Stute P12, Goulis DG13.
1Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Ring Road -Nea Efkarpia, 564 29 Thessaloniki, Greece. Electronic address: chdimo@hotmail.com.
2Department of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, and Department of Obstetrics and Gynecology, 'Dr. I. Cantacuzino' Hospital, Bucharest, Romania.
3Breast Clinic and Menopause Clinic, University Hospital, De Pintelaan 185, 9000 Gent, Belgium.
4Second Department of Obstetrics and Gynecology, National and Capodestrian University of Athens, Greece.
5University Women's Hospital of Tuebingen, Calwer Street 7, 72076 Tuebingen, Germany.
6Department of Obstetrics and Gynecology, Zaragoza University Facultad de Medicina, Hospital Clínico, Zaragoza 50009, Spain.
7Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
8Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
9Istanbul University Cerrahpasa School of Medicine Dept. of Obstetrics and Gynecology, Division of Reproductive Endocrinology, IVF Unit, Turkey.
10Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56100 Pisa, Italy.
11National Heart and Lung Institute, Imperial College London, Royal Brompton Campus Hospital, London SW3 6NP, UK.
12Department of Obstetrics and Gynecology, University of Bern, Switzerland.
13Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Greece.
Late-onset hypogonadism (LOH) represents a common clinical entity in aging males, characterized by the presence of symptoms (most usually of a sexual nature, such as decreased libido, decreased spontaneous erections and erectile dysfunction) and signs, in combination with low serum testosterone concentrations. Whether testosterone replacement therapy (TRT) should be offered to those individuals is still under extensive debate.
The aim of this position statement is to provide and critically appraise evidence on TRT in the aging male, focusing on pathophysiology and characteristics of LOH, indications for TRT, available therapeutic agents, monitoring and treatment-associated risks.
Literature review and consensus of expert opinion.
RESULTS AND CONCLUSIONS:
Diagnosis and treatment of LOH is justified, if a combination of symptoms of testosterone deficiency and low testosterone is present. Patients receiving TRT could profit with regard to obesity, metabolic syndrome, type 2 diabetes mellitus, sexual function and osteoporosis and should undergo scheduled testing for adverse events regularly. Potential adverse effects of TRT on cardiovascular disease, prostate cancer and sleep apnea are as yet unclear and remain to be investigated in large-scale prospective studies. Management of aging men with LOH should include individual evaluation of co-morbidities and careful risk versus benefit assessment.
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Aging male; Late-onset hypogonadism; Testosterone replacement
Four myths about allergies you thought were true – but aren't
June 5, 2015 1.49am AEST
Sally Bloomfield
Honorary Professor, London School of Hygiene & Tropical Medicine
Sally Bloomfield is Chairman of the International Scientific Forum on Home Hygiene. This is a not for profit Charitable Trust, which is funded by an educational grant and project funding from the private and public sector
I can't believe it isn't true. Hayfever by Shutterstock
Allergies are on the rise across the developed world and hay fever and eczema have trebled in the last 30 years. Yet allergies are an area of much confusion and concern. Although one study found 38% of people think they have a food allergy, in fact only 1-5% do, and allergists commonly report spending most of their consultations refuting firmly held beliefs that have no scientific foundation.
Theories about allergy – some from medical research and some from lifestyle "gurus" – have led to conflicting information, making it hard to know what to believe. Because of this,Sense About Science worked with me and a number of allergists, immunologists, respiratory scientists and pharmacists to produce Making Sense of Allergies, a guide tackling the many myths and misconceptions about allergies. One common myth – something that I work on – is the link between allergies and exposure to microbes.
So here is a hygiene and allergy reality fact check:
Do fewer childhood infections mean more allergies?
No. Although a link between allergies and microbes is largely accepted, the idea that more infections during childhood reduces the chance of developing allergies is now discounted. This idea came from the hygiene hypothesis, proposed in 1989, which theorised that the 20th century's increase in allergies was due to lower rates of infection in early childhood. This hypothesis was based on observations that larger family size protected against hay fever, while smaller families were thought to provide insufficient infection exposure because of less person-to-person infection.
Infection not protection. Ill by Shutterstock
Exposure to a normal range of microbes during the first months after birth is critical to developing the immune system, but there is no evidence that "regular" infections are important to boost general infection immunity or prevent allergies.
Are allergies up because of modern obsessions with cleanliness?
No. Our microbiomes, the population of microbes that live in and on our bodies, have altered from previous generations. This is not because of cleanliness, but because we interact with less diverse microbial environments than those of our largely rural ancestors. The idea that excessive cleaning has created "sterile" homes is implausible: microbes are rapidly replaced by organisms shed from us, our pets, raw foods and dust.
Not such a bad thing. Washing by Shutterstock
This understanding has come from the "old friends" mechanism, a refinement to the hygiene hypothesis that offers a more plausible explanation for the link between microbial exposure and allergies. It proposes that exposure to the diverse range of largely non-harmful microbes or parasites that inhabit our world are important for building a diverse microbiome that is vital for sustaining a well regulated immune system that doesn't overreact to allergens like pollen. These "old friends" have co-evolved with humans over millions of years. By contrast most infectious diseases only emerged over the last 10,000 years as we came to live in urban communities.
Old friend microbes are still there, but we have lost contact with them due to lifestyle and public health changes over the past two centuries. Improved water quality, sanitation and urban cleanliness have massively reduced infectious disease, but inadvertently deprived us of exposure to these microbes. Changes in microbial content of food, less breastfeeding, more caesarean sections, urban rather than rural living and increased antibiotic use have also reduced early life old friends interaction.
Will relaxing hygiene reverse the trend in allergies?
No. We now know that relaxing hygiene will not reunite us with our old friends, but carries the risk of increased exposure to other microbes that can cause old and new diseases. Because it was originally called the "hygiene" hypothesis, and because the terms hygiene and cleanliness are used interchangeably, people often assume that "being less clean" implies being less particular about hygiene.
At the same time that allergies have increased, the threats of global pandemics and antibiotic resistance have increased, and hygiene is key to containing these threats. Protecting against infection is not about how clean our homes look or how often we shower, it's what we do to stop germs spreading.
By using "targeted" hygiene practices such as hand washing, food safety and toilet hygiene, while encouraging everyday interactions with our microbial world we maximise protection against infection, while maintaining exposure to old friends.
Are synthetic chemicals linked to rising allergies?
No. Excessive use of cleaning and personal care products and antibacterials is sometimes said to be linked to allergies because it deprives us of microbial exposure. Antibacterial products are perceived to exacerbate this. However, because evidence suggests that general day-to-day home cleaning has no impact on microbial levels, it is unlikely to impact on our human microbiome. By contrast targeted disinfectant use, for example while preparing food, can reduce infection risks.
Counting the number. Test by Shutterstock
Many people believe that "man-made" chemicals are more likely to cause allergic reactions, leading to many synthetic substances in products being replaced by "natural alternatives". However, the most common allergic reactions are to naturally occurring allergens, in foods such as eggs, milk and nuts, in common garden plants such as primroses and chrysanthemums, and things in the environment such as pollen, dust mites and pet dander. Some natural replacements for synthetic substances could actually increase the risk of allergic reactions.
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