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Evaluating Endocrine Disruptor Research

Published on July 30, 2015

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Every now and again, we see a flurry of press releases flooding social media about new research purporting to prove that endocrine disruptors are safe. Most recently, the press has been focused Bisphenol A or BPA. New FDA proclamations suggest that it has no impact on health. When one reads the actual research upon which these statements are based, it says no such thing. Unless of course, the research is funded by industry, then it is almost always positive. A report in Newsweek found:

In 2013, for example, the American Chemistry Council spent more than $11 million on lobbying expenses, according to the Center for Responsive Politics. Industry groups have also funded, and in some cases written up, research done by governmental scientists. One 2008 investigation, by the Milwaukee Journal Sentinel, found that “a government report claiming that bisphenol-A is safe was written largely by the plastics industry and others with a financial stake in the controversial chemical.”

The report goes on to state that the FDA

…dismissed as irrelevant the vast majority of the BPA safety studies its own scientists reviewed in preparation for that official position statement. According to the FDA, for example, all of the 48 epidemiological studies reviewed had ‘no utility’ for the agency’s risk assessment, the formal process it undertakes to decide if a chemical is safe for human health or not.

With such contradictory claims about safety, who should we believe? How do we evaluate the safety research about endocrine disruptors? Here is a primer.

Industry Sponsored Research Is Biased

In a mini-review of research on bisphenol A (BPA) – the endocrine disruptor in plastics, of the 115 studies published on adverse effects of BPA 81.7% (94) reported significant adverse health effects (2004). However, upon review, it was found that 90% of the government funded, academic research found significant adverse effects while 100% of the industry-sponsored research found no ill-effects of BPA – none. This is a common theme across all industries – pharmaceutical included. When billions of dollars are on the line, industry sponsored studies will show favorable results more often than not. Always check the author’s conflict-of-interest disclosures at the back the article. If none are reported though, don’t assume they do not exist. Not all conflicts of interests are disclosed. You may have to do additional digging to identify conflicts.

FDA or EPA Approved Does not Mean Safe or Risk-Free

Both agencies have long histories of approving and then failing to recall dangerous chemicals, drugs and devices from the market. Their work is particularly incompetent in reproductive (endocrine) and women’s health: thalidomide, DES, Yasmin/Yaz, HRT, Mirena, Prolift to name but a few that have garnered the seal of approval by the FDA. Phthalates, BPA, Glyphosate for the EPA. Remember the EPA doesn’t even study the female reproductive dangers unless research shows that a chemical impacts the male reproductive system.

Research Methods Matter

Perhaps more so than in any other field of science, endocrine research requires serious consideration of all aspects of the study protocol. This means that you cannot rely on a press release about the research to determine the study’s relevance. You must read the original research and evaluate the methods. (Reading original research is a good habit to have for all matters that affect your health and well-being). Once you pull the research, here are some things to consider.

Length of study. Most hormone reactions are longer term and span generations. If the study is short duration, as in the case with the industry sponsored GMO research or doesn’t include third generation effects, as with BPA research – question the results.
Population studied. Whether one is investigating a chemical or a drug in humans or in rodents, the sample population matters. Ascertaining safety of efficacy by testing only healthy young men, when the drug or chemical is meant for the real world where women, children, elderly, healthy and not so healthy individuals reside, is common practice and recipe for disaster. Same is true for rodent research – the strain, sex, age and health of the animal must be considered if the work is to be extrapolated to real humans. I read one study claiming that BPA was safe, but they used a strain of rats that was resistant to environmental estrogens. Of course, BPA’s estrogens would not affect these estrogen-resistant rodents.
Outcomes measured. What does the study measure and how does it evaluate change? More often than not, industry sponsored research will not measure the appropriate endpoints or reproductive dangers. Sometimes this is sleight of hand, other times it is simply ignorance of the endocrine system’s far-reaching regulatory control. In either case, one has to evaluate what the study actually measures before determining its validity. Here, you can use a bit of personal experience – what systems, organs or behaviors are affected by your hormones? If the study didn’t measure any of these variables, then it’s probably not a very solid protocol.
‘Gold-standard’ protocols are not always golden. It takes years, decades even for ‘gold-standards’ to become the accepted methods – often well after their utility has run out and newer, more sophisticated tools have reached the market. This has been the case for endocrine testing and endocrine disruptor evaluation. If a study rests all of its findings using a gold standard, it may not be using the most sensitive testing methods.
Clinical significance is not the same as statistical significance. Clinical significance means the chemical/drug has some meaningful impact on the health or well-being of the individual or animal. Statistical significance is just a math equation. A simple increase in sample size while limiting or ‘restructuring’ outcome variables is all it takes to derive statistical significance in most research. Does that mean the drug or chemical has clinically relevant health effects – not necessarily. The opposite is also true. Want to obfuscate the dangers of a drug/chemical? Do a huge study (preferably by combining dozens of poor quality individual studies into a meta analysis), throw everything but the kitchen sink into the analysis, do simple stats and highlight the lack of statistical significance in the death or injury rates. Only a small fraction of the study population died – but it wasn’t statistically significant, so the drug/chemical is considered safe. If the study does not study distinguish between clinical and statistical significance or downplays the death and injury rates as statistically insignificant, approach cautiously.
Hormone reactions do not conform to linear statistics. Damn it, how dare our complex physiology not conform to the simplicity of linear statistics. A common dose-response curve is highly linear, where a small dose elicits a similarly small response and a larger dose increase the response size. This is not case when dealing with endocrine disruptors. Hormone systems are complex and highly non-linear. Hormone dose-response curves are often in the shape of an inverted U where low doses elicit huge responses, mid-level doses elicit minimal responses and high doses again elicit huge responses. And so, any study measuring hormone effects using simple, linear, dose response calculations is bound to miss the effects entirely.
Hormones have metabolites (as does everything else). Metabolites evoke their own reactions. We know that some of the metabolites from BPA are stronger, 1000X stronger in fact, than BPA itself. Studies that don’t address the full complement of hormone products that circulate in our bodies as a result of exposure to something like BPA will severely underestimate the safety issues.

In a nutshell, we have to do our homework. There is no simple ‘Good Housekeeping Seal of Approval’ for products that impact health and well-being. We wouldn’t trust the marketing put out by car manufacturers or, worse yet, a car salesmen, about the safety, gas efficiency, repair history and comfort of a new/used car; why do we trust the makers of chemicals to give us the straight story. We shouldn’t. We have to become educated consumers of health research in order to protect ourselves.

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This article was published previously in March 2013 and updated and edit for republication in 2015.

Tea and Healthy Blood Sugar Levels

by Lauren Chmiel

Published on July 16, 2015

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It seems to be an almost daily occurrence I am hearing or reading about correlations between specific consumables and better health, whether it is the acai berry, resveratrol or the previously disparaged coconut oil. While some “superfoods” wax and wane in popularity, the benefits of consuming tea continues to intrigue academics, medical professionals and the general public alike. Countless studies have been conducted in order to prove there is a solid relationship between tea consumption and lowering blood sugar levels, or that tea can serve as an inexpensive, alternative method for prevention of diabetes and its pre-diabetic metabolic precursors.

Specifically, I think it is important to sort out the relationship between managing diabetes and how tea can serve as a useful tool in doing such. Diabetes is a complex, chronic disease which, essentially, develops when the pancreas produces too little insulin (Type I) or one’s body can no longer respond to insulin (Type II). Diabetics suffer from blood sugar levels above the healthy range, and when left untreated, can result in a number of debilitating complications. Type II Diabetes, the type which develops usually in adulthood, heavily depends on our lifestyle choices (e.g., diet and exercise). According to the American Diabetes Association, 25.8 million Americans (adults and children), or 8.3% of the population, suffer from diabetes as of 2011. The World Health Organization (WHO) estimates that over 347 million individuals worldwide are diabetic, and approximately 90% of this number has Type II Diabetes.

As an undergraduate, I had the pleasure to conduct research regarding the relationship between Diabetina, an herbal tea blend from Mexico, and blood sugar levels in normal glycemic-level individuals. Although my results were statistically inconclusive, I did notice that Diabetina and black tea consumption (which my participants consumed for a total of 16 weeks) resulted in lower, healthy blood sugar levels. A number of studies concerning black or green tea consumption and blood sugar have proven to be rather promising. A 2012 academic article published in BMJ Open and reviewed in The Huffington Post and WebMD suggests that countries with high black tea consumption patterns have significantly lower rates of diabetes. Nations known for high tea consumption such as Ireland, UK and Turkey enjoyed the lowest levels of diabetes out of the 50 countries surveyed in this study. Green tea and black have both been touted as useful for lowering glucose levels, and in rat studies, have proven to inhibit diabetic cataracts.

It is perfectly acceptable to wonder, what is it about tea that works with lowering our blood sugar? Black, green and oolong teas all are derived from the Camellia sinensis plant and are known to contain polysaccharides which prevent absorption of glucose (sugar) in the body. The relationship between the human race and tea consumption stretches back for at least 5,000 years and has enjoyed a long, colorful life, stemming from its supposed invention by the Chinese Emperor Shennong and has been a prominent member of European history since the late 16th and early 17th century. Not only has the ancient ritual of tea drinking been cultivated for millennia, tea consumption may serve as a healthful participant within a well-balanced diet.

In consideration of everything I have previously mentioned, some current research suggests that one must consume a good amount of tea in order to prevent or reduce one’s risk of diabetes. A European meta-analysis published in May 2012 suggests that consumption of four or more cups of tea a day is associated with a 20% lower risk of diabetes. Those who drink one to three cups of tea daily did not lower their risk of diabetes, comparable to non-tea drinkers. Green tea especially is credited as beneficial for a number of functions, such as deactivating free radicals and boosting metabolism.

We live in a world of modern medicine and often, natural methods of healing are overlooked or dismissed. Perhaps we shouldn’t be so quick to overlook these remedies. As the Pacific College of Oriental Medicine states, “green tea is not a cure for diabetes, but a natural gift for restoring balance in the human system and removing unwanted toxins accumulated from the internalizing of the environment.” In other words, tea may not cure diabetes, but it could be a part of healthy lifestyle, and as my research demonstrated, it might just lower your blood sugar.

This post was published previously in January 2013.

Antibiotics during Pregnancy: Finally Pharmacokinetic Research

by Chandler Marrs, PhD

Published on February 5, 2015

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A common refrain of mine is the lack of drug testing in women, especially pregnant women and relative to the enormous hormone changes women experience across a cycle, across pregnancy or postpartum and frankly across the lifespan. Hormonally, a 16 year old is not the same as a 45 year old. A woman’s biochemistry is not the same early in her cycle as it is late in her cycle. Nor is it the same when she is on oral contraceptives or hormone replacement therapies compared to when she is not and most especially, the pregnant woman’s biochemistry is hugely different than that of a non-pregnant woman. And yet, despite the lack of testing, lack of data, and limited understanding about how medications work relative to a woman’s hormonal state, women, pregnant and non-pregnant alike, are routinely prescribed medications for which we have a very poor understanding of the basic pharmacokinetics (how a drug travels through the body) or pharmacodynamics (what it does and how it works).

Ever so slowly, this may be changing. A group of researchers from the University Chicago, recently published a study on the Influence of Body Weight, Ethnicity, Oral Contraceptives and Pregnancy on the Pharmacokinetics of Azithromycin in Women of Childbearing Age. Though the study was small with only 53 pregnant women and 25 non-pregnant women, it represents one of the few published pharmacokinetic studies done on a drug routinely prescribed to pregnant women that evaluates hormone state.

Azithromycin: the Most Common Antibiotic Prescribed During Pregnancy

Azithromycin, more commonly known as Zithromax, Azithrocin, Z-Pack or ZMax, is the most frequently prescribed antibiotic for a range of bacterial infections of the ears, skin, throat. It is believed to be safe during pregnancy, despite having a pregnancy category rating B (a designation given a medication that has not been tested in human pregnancy but appears to be safe in animal studies). Some research shows that Azithromycin appears to have no more adverse reactions than other antibiotics, but whether it is truly safe, whether pregnant pharmacokinetics are different than non-pregnant or how they are different had never been determined. The University of Chicago study demonstrated what many have always suspected:

pregnant women metabolize medications differently (more slowly) than non-pregnant women
oral contraceptives slow drug metabolism
and interestingly enough, African American women show different pharmacokinetic patterns than Caucasian, Hispanic, Pacific Islander or Asian women

Pharmacokinetics: The Basics of Drug Disposition

The disposition of a drug (how it travels through the body), is affected by a number of physiological variables including plasma volume (greater when pregnant, lower when dehydrated), protein binding (fat soluble drugs travel through the system bound and protected from metabolism-preparation for excretion- by carrier proteins), liver and kidney function (our waste removal systems). Any alteration to these variables affects how long a drug stays in the body, how much of the drug is available to exert its effects on the tissues or organs, and how effectively it is cleared from the system. Determining the disposition of the drug- the pharmacokinetics- is very important for drug dosing and ultimately, safety. Every one of those drug disposition variables is affected by the hormone changes of pregnancy, postpartum (menstruation, menopause, oral contraceptives, HRT, etc.).

In the case of Azithromycin, pregnancy significantly slowed metabolism and clearance of the drug in pregnant Caucasian, Hispanic, Pacific Islander and Asian women, but not apparently in African American women or women not taking oral contraceptives. Translated, this means that pregnant Caucasian, Hispanic, Pacific Islander and Asian women were exposed to more drug, for a longer period of time, than were African American women. Ditto for women taking oral contraceptives versus those who were not taking oral contraceptives.

The researchers did not investigate whether hormonally-related changes in immune function interacted with the pharmacodynamics of the drug–rendered it more or less clinically effective. Nor did they evaluate whether or how other medications may have influenced drug disposition. As an aside, women in the pregnant group were taking more medications, in addition to the antibiotic in question, than the non-pregnant group.

What this research does show, however, is that hormones, or at least ‘hormone state’ affects drug disposition significantly. Additional studies are needed to determine how and if more customized dosing is required in pregnant and non-pregnant women alike.

This article was posted previously in September 2012.

BPA and Other Gender Bending Plastics

by Chandler Marrs, PhD

Published on February 2, 2015

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An oft repeated theme in this journal is that measurement matters. From the basic concept that one cannot manage what is not measured to the more specific notion that research protocols in the lab should attempt to mimic real life as much as reasonably possible, we believe measurement is critical. In matters of health and hormones where complex systems with a myriad of ever-changing variables are the norm, this is difficult at best. Sometimes, however, the simple act of measuring these variables opens a world of insight. This is the case with BPA and other estrogenic plastics.

BPA and Estrogens

Bisphenol-A (BPA), the estrogenic activator leaching sperm from our men and damaging the ovaries of women came to the world’s attention several years ago after a vocal and strident outcry from moms. The FDA subsequently remitted, prohibiting BPA from baby bottles and sippy cups and a slew of newer ‘safer’ BPA-Free plastic products emerged, but are they really safer? Maybe not.

Simulating Real Life Usage: Measurement Matters

Until recently, no one had measured the estrogenic activity of the other compounds used to plasticize our food containers. Nor had anyone measured these compounds under real-world stressors, such as UV-radiation (sunlight), microwave radiation or in the dishwasher or with different types of solvent (to represent the food/drinks contained by these plastics). Indeed, as is often the case, we were lulled into a false sense of safety. We believed that since BPA was removed from plastics, the endocrine disruptors were also removed, when in fact the other compounds had simply not been measured.

As one might expect, once those tests were conducted, researchers found that most plastic products on the market today release chemicals that are estrogenic – even those marketed as BPA-Free. Baby bottles, where much of the BPA outcry began, can leech as many as 100 different chemicals especially when exposed to real-life stressors, sunlight, microwaves and dishwashers, all estrogenic in nature.

Sunlight, in particular, was especially adept at maximizing the release of estrogenic chemicals into the solvent. Who hasn’t left their water bottle in the car? And when the plastics were tested in both polar and non-polar solvents (most foodstuffs/drinks are a combination of both), the majority showed reliably detectable estrogenic activity.

What to Do With All of These Estrogens

Not to worry, according to the authors of the study, there are ways to create plastics that don’t elicit estrogenic activity and they don’t cost any more or require different manufacturing than those that do. It’s simply matter of choosing to utilize those plasticizers and associated chemicals instead of what we currently use. The question is whether major plastics manufacturers will pay heed to these warnings and make the switch. Did I mention the man-boobs and infertility from the extra estrogens?

The study: Most Plastic Products Release Estrogenic Chemicals: A Potential Health Problem That Can Be Solved

Postscript

The article above was published originally in October 2012. Over two years later, I am sad to say that not much has changed. Industry has repeatedly denied the safety issues with BPA and the other, presumably safe, BPA-free plastics. The current campaigns, much like those of the tobacco industry, proffer industry financed research as proof of product safety while discrediting any scientist who brings evidence to the contrary. It’s a common script followed by all chemical manufacturers; one that has yet to be successfully curtailed.

The Truth About Salt

by Angela A Stanton, PhD

Published on December 29, 2014

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When we salt our food, we rarely think of salt as a crucial aspect of our physiology. In particular, we think it has absolutely nothing to do with anything other than taste and we certainly do not think of hormones. In this short post, I would like to clarify a few myths about salt and salt types and hint at their importance and hormonal connection.

The Myths of Designer Salts

Myth #1 sea salt versus table salt. There are hundreds of posts on the Internet about the benefits of sea salt over table salt. I would like everyone to know that there is only one salt on planet earth: sea salt. The fact that it may be called table salt simply suggests that some time ago it was clearly understood by all that all salt came from the sea. There was no need to place the word “sea” in front of salt; we all knew what it was. Somehow we have forgotten that salt comes from the sea. Now many designer salts have showed up with the word “sea” in front of the word salt and sell for much more than table salt. Don’t be fooled: all salts come from the sea! Preferences, of course, may mean you pick a designer salt over table salt, but I would like to make sure you know that in terms of salt, they are the same for the body.

You may ask: how can they be the same for the body if one contains all kinds of other elements as well as pure salt itself. The answer is very simple. In the body, salt molecules (NaCl) break down into ions (Na+ and Cl-) and only these two ions participate in what is called voltage activated sodium pumps (Na_v1.1-1.9) where 1.1 to 1.9 indicates that there are 9 such pumps and Na_v stands for voltage activated sodium pump. Thus, for the body only ions matter. Na+ is inside the cell and is positively charged. Cl- is outside the cell and is negatively charged. The two create the voltage necessary for the cell to function. Some of these pumps also have additional functions—such as sending pain message when a pump opens and does not close properly. The influx of Na+ and Cl- can cause the signal of pain to go off causing chronic pain. Much is yet to be understood by the function of salt but the one thing we already know: salt is NaCl and no additional organic matter matters.

Myth #2 refers to rock salt that comes from mountains like the Himalayas in various colors. They make beautiful lamps but in reality they are sea salts that have fossilized as the tectonic plates have shifted and lifted the Himalayans out from under the sea. Why are they pink or orange and very colorful in general? Because as the mountains were lifted, pressure increased on the salt deposits and the weight of the mountain pressing heat and metals through the salt created fossilized salt with various metals trapped in the salt itself. There is nothing wrong with eating fossilized rock salt except that by the nature of the fossilization process of high heat, pressure, and the many metals, a large percentage of these “minerals” entrapped in the salt are actually radioactive metals. Again, it is a taste question whether you prefer Himalayan or other salt but know what you are getting.

Myth #3 is Celtic and similar sea salts of various colors that are collected from clay pools and evaporated such that each sea salt crystal has little cavities of entrapped water with “minerals.” I see many lists of minerals for various sea salts but few of us actually consider where those minerals come from. I know we all love to eat sea food, fish, shellfish, and sea weeds as well. The mineral deposits in designer sea salts come from the debris of these sea animals, including their excrement and dead bodies. There is nothing wrong with eating fish poo and dead fish as long as you know that your choice of salt contains it. Some of these salts are proud to also include a bit of clay, and hence, the moisture must be kept else you will need a hammer and chisel to break the salt up. So, much of the charm about designer salts is trickery and harmless misinformation that takes advantage of those who are not aware.

The truth: salt, by chemical composition Sodium-Chloride (Na+, Cl-) is only these two elements combined, as discussed above. Our bodies use these chemicals only in ionic form. Salt is part of the baby’s amniotic fluid in our bodies (not Himalayan salt, and not various colored sea salts; just simple Na+ Cl-). This standard chemical element constitutes a very large part of the over 70% saline brine of our bodies. We are made of salt water. When we visit the emergency room with any illness, the most often used first step – the needle with a clear liquid dripped into our vein – is also saline water electrolyte. Electrolytes contain other elements to complete the full list of micro and macro nutrients of the 70% brine.

Other Minerals in Salt

What about the so called “minerals” that are in the designer salts? Do we need them?

Magnesium is a very important element that provides a key such that the cells can open at all given the proper electrical environment. Magnesium also provides crucial nutrient for the mitochondria (little bacteria in every single cell of our body that converts the food we eat to energy packets our cells can use). You get more magnesium out of a bite of food (just about any food) than from an entire box of designer salt.
Calcium is needed for high voltage channels where the neurotransmitters are released.
Potassium is needed to keep the balance of hydration in the cell and outside of the cell to ensure that the cell is not overly hydrated (potassium is a diuretic).
Phosphates. We also need phosphates and other elements and of course a ton of water, but the elements in designer salt sold as essential mineral are minuscule and meaningless.
Iodine. Another important factor is iodine. Designer salts do not contain iodine. In the US, the government has gone through great trouble placing iodine into our salt to eradicate goiter, a disease of the thyroid. Without adequate iodine our thyroid is not able to produce the right amount of hormone to keep our brain healthy. Recall also, in Japan after the nuclear plant released all that radiation, the first item sold out throughout the country was iodine. Iodine acts like a sponge, soaking up many toxins from our body to be able to eliminate them. Radioactivity is one of those things iodine can help clear from our bodies.

Salt and Hormones

So the question then is: what does salt have to do with our hormones? Does it matter? Indeed, it does. Those who have read the migraine series 3-part posts know that the most critical element in preventing and treating migraines is salt. Every single neuron in our brain has several voltage-gated sodium pumps (sodium-potassium pumps) to generate voltage. Without such voltage the neurons are not able to manufacture and release their neurotransmitters-hormones in the body. Thus, restricting salt in your diet retards the hormone manufacturing of your body. In previous articles, I showed how studies show that low salt diets are harmful even for those with preexisting heart conditions and hypertension. Salt does not increase blood pressure, provided that salt is consumed with sufficient amount of water, along with potassium and the other minerals and nutrients, I listed above.

Sodium retains water thereby hydrating the cells. Sodium chloride maintains the polarity differences between the inside and the outside of the cell membrane to control the electrical activity, which then open the pumps. Having enough salt in your brain makes the difference between having a headache/migraine or not. What if it also helps prevent other diseases of the brain? There are suggestions that fibromyalgia and neuropathy may be connected to one of the Na_v pumps. I wonder if other conditions such as bipolar disorder, anxiety disorder, and even depression could be, at least partly, caused by an inappropriate level of sodium in the brain?

Possible Role for Sodium – Potassium Pumps in Disease

Let’s investigate one of the voltage activated sodium pumps. The one we seem to know most about so far: Na_v1.7. According to recent research, this particular pump has a critical role in chronic pain dampening. Experiments on various poisonous animals—including the Chinese red-headed centipede and the snake black mamba—show that their venom seems to selectively choose this particular pump to dampen the pain associated with some types of chronic pain. The pain signals need not be located in any one particular location of the body, but are relayed by the brain as hormones release for the pain message. People with neuropathy, such as Type 2 Diabetes or those who have been been floxed (suffered an adverse reaction to a fluoroquinolone antibiotics) are very familiar with this pain. Nothing seems to help with this type of pain except a very few types of strong drugs of the brain, some (like Gabapentin) inhibit nearly all activities in the body in near-full-force. The drugs of the brain are systemic whereas the venom is capable of acting on only one sodium-potassium pump, the Nav1.7. Perhaps, in the future, this finding can be applied to reduce neuropathic pain without global nervous system dampening.

My Two Cents

I suspect most ailments of the central nervous system that include a hyper-sensitivity for pain will become a subject of sodium pump malfunction research. There are also indications that there is a switch in the connection of the peripheral nervous system to the spine, and thereby the central nervous system, where there should be a relay station to either inhibit or amplify the pain. Apparently, at this relay station the switch is flipped backwards and what should be inhibiting actually amplifies. Pain experienced from these crossed wires is called allodyna. I suspect we will be hearing much about this term in the future and how it connects to various sodium pump malfunctions that today we do not yet understand.

Sources:

Pain Scientific American December 2014; p:62-67

Migraines and Hormones: Behind the Curtain

by Angela A Stanton, PhD

Published on December 15, 2014

7193 views

Before puberty, migraines are three times more frequent in males than in females but after puberty the tides turn and females are more likely to suffer from migraines than males. An Oxford study found that females are twice as likely to have migraines and that

“brains are deferentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs.”

The overwhelming belief is that the connection is clear: the hormones kick in for women at puberty and that must be the reason. This begs the questions: 1) Do males have the same hormonal problems before puberty as females do after puberty? If hormones are at root of the problems, then there must be some similarities, right? 2) If female hormones are responsible for migraines, do all females have migraines when they reach puberty? 3) Do migraines cease when hormones stop changing after menopause? 4) What about pregnancy or postpartum, how do hormones impact women then? And finally, 5) Do men stop having migraines after puberty?

Some of the answers to these questions will surprise you and may make you wonder if hormones have anything to do with migraines at all. In this post, I show you that while there are some connections between hormones and migraine they might not be the primary drivers of migraine. The relationship between hormones and migraine is not in the presence of hormonal changes but what those changes require in terms of brain energy, the lack of which causes migraines.

First, I would like to respond in quick the five questions I asked earlier: 1) Do males have the same hormonal problems before puberty as females do after puberty that causes them migraines? The answer to this is no. 2) If female hormones are responsible for migraines, do all females have migraines when they reach puberty? The answer to this also is no. 3) Do migraines stop after menopause? Many women have more migraines and some even start migraines in their menopause, so the answer is no. 4) Do migraine increase or decrease during pregnancy or postpartum? The answer is no during pregnancy, but yes postpartum. 5) Do men stop having migraines after puberty? No they do not.

It is not obvious that the cause of migraines must have anything to do with female monthly cycles and their associated hormones. Given also that many women have migraines after puberty, we are safe to assume that some other factors may play a role. It would be hard to envision a world full of children in which our evolutionary road took women to necessarily experience migraines with their menstrual cycles. So what is the connection to hormones; how do women end up with migraines; and why?

Rather than listing all the hormones that activate throughout the monthly cycle of a woman, let’s take a look at what is happening in the body of that woman backstage, during the hormonal changes. First, in a small review I cover in a few sentences what a migraine is.

Migraine is a collection of symptoms that have an underlying physiological mechanism based on chemical (ionic) imbalance in the brain. Migraine is a neurovascular event that Dr. Charles at UCLA called “spectacular neuro-physiological event” that changes the neurophysiology or chemistry of the brain itself. This can be seen using fMRI technology where oxygenation of brain regions shows where activity occurs during migraine—albeit this does not show why it occurs. The same article also suggests that though medications are available to treat the pain associated with migraines, half the sufferers do not receive any pain relief benefit from the drugs. I find this statement alone interesting because if migraine was truly understood, the pain medication would work for all. This clearly is not the case. To understand what is happening, we must think out of the box and leave behind the hormonal theory of migraines.

Moving Beyond the Hormone Migraine Theory

We now visit the female body all through a month. Let’s start two days after her menstrual cycle has ended. As female, we feel great, no pain, no bleeding, life is awesome. But what we don’t see works hard in the background using up important energy: the brain. Our hormonal changes are happening every moment of the day only we don’t feel it—hormonal changes are directed by the brain. Because we don’t feel the changes, we are ill-prepared for the inevitable day when it reaches a threshold point of not enough brain energy and the migraine starts. This typically happens 2-4 days prior to menses. I do not think migraines are caused by hormones, but rather they are triggered by the lack of energy available to the brain as the hormones cycle. When the brain runs out of energy, a wave of cortical depression begins in some part of the brain. This is what we feel as a migraine.

What actually happens that uses all that energy? After the menstrual cycle is over, the female body immediately prepares for the next menstrual cycle. There is no downtime for rest. The brain turns off one group of hormones and turns on others thereby manipulating how women see the world prior to and during estrus (fertile time). After a menstrual cycle is over, the brain turns on the estrogen to do a few things:

Prepare the uterus with a new fertile lining to accept the fertilized egg should one arrive and start a new life.
In order to make such fertilized egg happen, the egg must be prepared in the ovaries so hormones initiate the ripening of a new egg.
The woman’s body goes through amazing visible changes at this time of the month. If she had pimples, they magically disappear. If she was bloated, her bloating goes away. Her face becomes the most symmetrical it possibly can; the more symmetrical the more sexually appealing she becomes to the opposite sex.
She becomes extremely attracted to high testosterone males requiring her pheromones to change and to be able to sense a high testosterone pheromone male’s presence. This high testosterone attraction changes after estrus to attraction to low testosterone males for the safety of the child, should mating end in a baby.

With all this activity going on in the female body that she cannot feel, she is in danger of exceeding the threshold of brain energy-shortage without prior notice or preparation. The cost of all of these activities behind the curtains in the female body is very high in terms of brain energy and hydration. These are sex-hormonal functions that only exist for a certain period of time during the female life. Females are known to be born with all of their eggs they will ever ripen for possible babies. Only these eggs are not “ripe” at birth. Every month one egg ripens in one of two ovaries (sometimes in both and sometimes in none). This egg breaks out of the ovary and starts its journey down the ovarian tube where it either gets fertilized by a sperm or not. If the egg is fertilized, it attaches to the wall of the uterus lining—later to become the placenta of the baby—and a new life cycle begins in the mother-to-be. If however there is no sperm able to penetrate the egg, while it descends in the ovarian tube, the egg will have to be cleared from the uterus together with the nutritious blood vessel rich lining created. This happens with the menstrual bleeding. This we can see and feel.

My Theory: Why Hormone Changes are not the Cause of Migraines

As shown earlier, migraines are not equally present in everyone’s life. Other factors, such as genetic predisposition to sensory organ hyper sensitivities (SOHS) that require more energy, may be the cause. Recent research hints at ionic balance (meaning energy available for use) is crucial in maintaining optimal function and the slightest imbalance can cause major problems (Wei et al.).

When the body is tasked with demanding activities the cells responsible for completing those extra tasks are doing extra chores and need extra energy. The brain regulates the creation of extra hormones for the menstrual cycle. The brain manages the clearing of the uterus after the fertile layer was not used.

By the third day after the cycle, the brain is ordering an egg to ripen—this takes extra energy. This is a once a month event. The brain must have extra energy to complete this task. Ever tried to run a marathon on empty or run your car the extra mile without fuel in your tank? Not possible. Something must break. The brain is the logical one for those who are predisposed to SOHS. If their brain runs out of energy, the neurons cannot generate voltage and stop creating neurotransmitters that instruct the production of hormones in the body. This leads to cortical depression and migraine.

Migraine during Pregnancy

Hands up: how many of you had migraines during pregnancy? Up to 75% of migraineurs do not have migraines during pregnancy. Why you may ask? There is more than one reason for this. The first and most important reason is that while the mom-to-be is pregnant, she has no menstrual cycles so the brain has no monthly cyclical job and it need not use extra energy. Even if the pregnancy comes with a menstrual flow here and there—as it sometimes happens—there is no egg that ripens and there is no uterus layer to remove. It is only a bit of bleeding but no extra energy was needed by the brain for this menstrual flow.

The second important factor is that during pregnancy the mom-to-be seems is more cognizant of what her and her baby-to-be needs. She eat more, tends to eat what she craves and is less likely to be good-looking-body conscious during this time. Pickles with ice cream are famous cravings of women. All the nutrients the brain craves for re-creating energy and feed the brain to prevent migraines: salt, calcium, magnesium, and fat that converts to sugar in the brain.

Migraine during Postpartum

After giving birth nearly, nearly all women immediately revert to eating for a good looking body, lose all the baby fat, and get back into the size zero genes. They stop eating brain-healthy after pregnancy (they never realized they ate brain healthy the first place). Nearly all women return to their migraines postpartum as they return to their old dietary habits.

Post-Menopausal and Menopausal Migraines

We are often told that after we enter menopause or are post-menopausal, our migraines will disappear. Yet, I talk to many women, who have more migraines after their fertile period of life has passed. I am one of those women who experienced more migraines in menopause than in early life. Thus, being no longer fertile, no longer ‘hormonal’ does not mean that we become migraine free; further pointing to the lack of connection of migraines to hormonal fluctuations. In menopause, many women are still very body conscious and watch their dress size more than their health. Others, however, recognize the value of a body supporting diet that may not create a body to fit into such small jeans but may be healthier for an older woman. This second group probably stops experiencing migraines (like I did) whereas the first group remains dehydrated and lacks brain nutrition to work those SOHS brains. They end up continuing their migraines as they had them before.

Of course, we already know from my previous posts that migraines are genetic so not everyone abusing her body will end up as migraineur. To be migraine free, everyone, male or female, must follow the rules of brain fuel.

Fuel for Migraines (Hormonal or Not)

What exactly is the fuel for migraines of any kind? I am leading you back to the first post on migraine that tells you what nutrition the brain needs to return to energy and fuel-filled comfortable homeostasis. The brain works on electricity, which requires specific charge differences inside and outside the cell’s membrane. This voltage is created by salt (sodium and chloride) in ample supply. Sodium also retains water inside the cells for hydrations and opens the sodium-potassium gate to allow nutritional exchange. I am also linking you back to the second post on migraines that explains the anatomy of migraines and what actually happens when the brain in not in homeostasis. How a migraine starts is now visible in fMRI. If you follow the posts I linked to and read the book on how to prevent and fight migraines, chances are, you may never have to face another migraine in your life.

Sources:

Fighting the Migraine Epidemic; A complete Guide. An Insider’s View by Angela A. Stanton, Ph.D. Authorhouse, February 2014. https://www.amazon.com/Fighting-Migraine-Epidemic-Complete-Migraines/dp/154697637X/ref=tmm_pap_swatch_0?_encoding=UTF8&qid=1518636023&sr=8-1
Why Women Suffer More Migraines Than Men by Patty Neighmond, NOR April 16, 2012 3:17 AM ET http://www.npr.org/blogs/health/2012/04/16/150525391/why-women-suffer-more-migraines-than-men
Her versus his migraine: multiple sex differences in brain function and structure by Maleki et al. BRAIN. 2012: 135; 2546–2559, http://brain.oxfordjournals.org/content/brain/135/8/2546.full.pdf
Hormones & desire Hormones associated with the menstrual cycle appear to drive sexual attraction more than we know. American Psychological Association By Bridget Murray Law. March 2011, Vol 42, No. 3 Print version: page 44 http://www.apa.org/monitor/2011/03/hormones.aspx
Human Oestrus by Steven W Gangestad, Randy Thornhill. The Royal Society, Proceedings B May 2008 http://rspb.royalsocietypublishing.org/content/275/1638/991
Ovulating Women are STRIPPING Men of their Money. Cal Poly Bio 502 class lecture notes article. A blog about human evolution, economics, and sexual physiology. Why do strippers make more money at different times of the month? By Hayley Chilton http://physiologizing.blogspot.com/2013/01/ovulating-women-are-stripping-men-of.html
Migraine and Children. Migraine Research Foundation http://www.migraineresearchfoundation.org/Migraine%20in%20Children.html
Prevalence and Burden of Migraine in the United States: Data From the American Migraine Study II; Richard B. Lipton, MD; Walter F. Stewart, MPH, PhD; Seymour Diamond, MD; Merle L. Diamond, MD; Michael Reed, PhD. Journal Headache; 646:657
Population-based survey in 2,600 women. Karli et al., The Journal of Headache and Pain October 2012, Volume 13, Issue 7, pp 557-565 http://link.springer.com/article/10.1007%2Fs10194-012-0475-0
Multisensory Integration in Migraine Todd J. Schwedt, MD, MSCI. Curr Opin Neurol. Jun 2013; 26(3): 248–253
Unification of Neuronal Spikes, Seizures, and Spreading Depression. Wei et al., The Journal of Neuroscience, August 27, 2014 • 34(35):11733–11743 • 11733

Estrogens Doth Make the Heart Grow Sweeter

by Chandler Marrs, PhD

Published on September 30, 2014

4354 views

For years researchers have postulated the cardio–protective effects of the endogenous estrogens, namely estradiol. Research published in 2012 in the journal Hypertension identifies a mechanism by which the estrogens regulate heart function. It appears that systemic estrogen receptors (ER alpha to be specific) and by association estradiol, the hormone that binds to the estrogen receptors, are necessary to regulate cardiac glucose metabolism. Glucose is critical for maintaining heart contractility and mass.

Using both ovariectomized (ovaries removed) and knockout mice (genes that regulate the receptors are knocked out or removed, producing animals without estrogen receptors), researchers found that cardiac glucose metabolism was significantly impaired. When a drug that increases estradiol actions was given to the ovariectomized animals, cardiac glucose function was restored.

Estrogen Receptors and the Heart Muscle

In another study researchers found that the number of estrogen receptors located on the heart nearly doubles during end-stage cardiac disease. Moreover, the patterns and locations of these estrogen receptors differ significantly between males and females. Since males die from heart failure more frequently and more rapidly than females, researchers speculate that the increase in cardiac estrogen receptors is a protective, compensatory reaction that slows down and maybe even prevents heart failure.

Estrogen Receptors, Glucose and the Healthy Heart

Under normal circumstances, healthy hearts derive most of their energy from free fatty acids with only a smaller percentage from glucose metabolism. During ischemic events or heart attacks, the metabolic balance switches and glucose metabolism increases significantly. Since estrogen receptors appear to mediate cardiac glucose metabolism, it is likely that circulating concentrations of estradiol, the hormone that binds to the estrogen receptor, also plays a role in heart health or, more specifically, in its ability to survive and recover post heart attack. The estrogen receptor-cardiac glucose connection may be the mechanism leading to the higher survival rates for women, especially women with higher circulating estradiol (pre-menopause).

Diabetes and Estradiol

Interestingly, in diabetic patients the metabolic pattern is reversed. Rather than an increase in glucose metabolism post heart attack, free fatty acid metabolism increases making it difficult for the heart to generate sufficient energy to recover. Researchers speculate that this may account for the increased rate of heart failure in individuals with diabetes. Indeed, in experimental (rodent) models of diabetes, research show that diabetics have lower estradiol levels. The research in humans is mixed.

Hormones Matter

These studies point to the importance of steroid hormones beyond their role in reproduction. The interplay between steroid hormones and cardiac function is but one example of many where the traditional view and nomenclature of reproductive, sex, or female hormones has become outdated and likely limits our understanding of health and disease.

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Red Raspberry Leaf Tea to Relieve Menstrual Pain

by Lisbeth Prifogle, MFA

Published on August 21, 2014

13635 views

My alarm goes off at 0600 every morning. I groggily put on my sports bra and tennis shoes and start one of my many work-out DVDs to start my day. I do push ups, pull ups, lunges and squats all in order to build lean muscle tissue. The science behind this equation is easy – use your muscles to build muscle. But how can you tone muscles in your body that can’t be toned with weights or treadmills? The muscle I’m talking about is the uterus. The uterus or womb is lined with muscles that are primarily designed for childbearing which as we all know gives way to that monthly visitor that brings a suitcase full of cramps, bloating, heavy cycles and more. What if I told you that there is an all natural remedy with no side effects that also helps regulate menstrual cycles, treat cramps, aid in fertility, even lessen the chance of miscarriage, and help labor? Interested?

While there have been very few studies on the effects of red raspberry leaf tea (tea made from the leaves of the raspberry plant), it has been used for thousands of years to tone the uterus for fertility and menstrual problems. Studies have concluded that there are no side effects of this natural remedy. Raspberry leaf tea is full of nutrients including iron, calcium, manganese and magnesium, vitamins B1, B3, C, and E.

In the past, I have tried synthetic hormone treatments to deal with irregular periods, heavy bleeding, and cramps. I suffered through severe side effects including heavy bleeding in between cycles, severe depression and of course, cramps. I decided to try raspberry leaf tea because it had no side effects, could be bought at the grocery store or online, and even if it didn’t work for my specific problems it was still very nutritious. After drinking 1-2 cups a day for about two months I noticed a significant change in the regularity and severity of my cycles.

While I can tone my arms, legs and abdominal muscles through weight and cardio routines, I continue to use red raspberry leaf tea to tone my uterus and reproductive system. Does anyone have other experiences with raspberry leaf tea to share? Any successful fertility stories through this ancient elixir?

Bonus: For an all natural beauty product try applying cold tea or tea bags to your face as an astringent to tone your skin and treat acne.

Hormones Matter

Where health, hormones, and a whole bunch of other stuff, make sense.

hormones - Page 4

Evaluating Endocrine Disruptor Research

Industry Sponsored Research Is Biased

FDA or EPA Approved Does not Mean Safe or Risk-Free

Research Methods Matter

We Need Your Help

Tea and Healthy Blood Sugar Levels

Antibiotics during Pregnancy: Finally Pharmacokinetic Research

Azithromycin: the Most Common Antibiotic Prescribed During Pregnancy

Pharmacokinetics: The Basics of Drug Disposition

BPA and Other Gender Bending Plastics

BPA and Estrogens

Simulating Real Life Usage: Measurement Matters