Stalking the Elusive REM: The Biochemistry of OTC Sleep Aids


Confronting insomnia.Many of us have trouble falling asleep or staying asleep. There are several non-prescription options to help with this. This is a review of how those options affect sleep, as well as cautions to observe when choosing a sleep aid.


Anybody who has taken the allergy medicine Benadryl or its associated generic (diphenhydramine) has probably noticed that it can make you really drowsy. In fact, diphenhydramine is a common ingredient in medications with words like “PM” or “Night Time” in their names. Other anticholinergics, such as those found in motion sickness medications, also cause sleepiness.

One might be tempted to use diphenhydramine as a bedtime sleep aid. However, recent research (2015) indicates that this is not a good idea. The Adult Changes in Thought (ACT) study followed about 3,500 seniors over time. It found that those who had taken anticholinergics such as diphenhydramine regularly for three years or more had a 52% higher risk of dementia (especially Alzheimer’s disease) than did those who had taken these medications for a short period (a month or less).

How could anticholinergics be related to dementia and memory loss? As their name suggests, they work by antagonizing, or reducing the uptake of, acetylcholine. There is extensive research showing that acetylcholine plays a key role in the normal functioning of memory, particularly in the formation of memories. One of the ways acetylcholine contributes to memory formation is by increasing the activity of NMDA (N-methyl-D-aspartate) receptors in the brain. Therefore, it makes perfect sense that drugs that suppress the action of acetylcholine would be associated with disorders involving memory, such as Alzheimer’s.

Acetylcholine is an important neurotransmitter. In addition to its role in memory formation, it activates muscles and regulates excitatory responses in the peripheral nervous system. In the central nervous system, it helps sustain attention while we are awake. While we are asleep, it promotes REM (rapid eye movement) during sleep.

This means that diphenhydramine, which suppresses acetylcholine, in turn inhibits REM sleep. Since REM sleep is essential to awakening mentally refreshed from a night of sleep, diphenhydramine is not a particularly good sleep aid. Although it helps people drop off to sleep, it does not produce a good quality of sleep.

What if you have been taking anticholinergics, and would like to increase the amount of acetylcholine in your body to help repair memory deficits? Acetylcholine is not available in food sources, but it is built from choline, in which particular foods are rich. These include eggs, various kinds of liver, salmon, low-fat dairy, Brussels sprouts, peanuts, and wheat germ.


Valerian root, which comes from a flowering herb, is known for its efficacy in relaxation and sedative effects. By increasing the amount of the neurotransmitter gamma aminobutryic acid (GABA), valerian helps calm the nerve cells in the brain, reducing anxiety. GABA counterbalances the action of the excitatory neurotransmitter glutamate, helping to keep the brain from being, literally, overexcited. For people whose insomnia is caused or compounded by anxiety or a “racing mind,” valerian can be especially helpful.

Valerian has been clinically proven to significantly improve sleep quality, including rapidity in entering slow-wave sleep (a restful, deep sleep), reduced sleep disturbances, and an increase in the percentage of REM sleep.

Valerian may slow down how quickly the liver metabolizes certain common prescription drugs (such as statins and tricyclic antidepressants), as well as alcohol. If you are taking prescription medications, be sure to check with your pharmacist or physician about drug interactions. Caution should also be taken in combining it with black cohosh, another herbal remedy. The NIH warns against taking it if you have liver disease, although none of the compounds in it are known to be hepatotoxic.


Melatonin is a naturally occurring hormone (produced by the pineal gland, in response to darkness) that can be taken as a supplement. It has been clinically demonstrated to improve perceived sleep quality and to reduce awakenings, even in settings in which noise and light are present.

There are anecdotal reports that melatonin is associated with increased vividness and, to some degree, bizarreness, in dreams. However, the experimental evidence for this is weak, and it appears to vary from individual to individual. Most people tolerate it well.

Melatonin is considered quite safe, especially in the short term (up to two years of regular use); long-term effects have not been studied. Melatonin can interact with some prescription drugs (such as anticoagulants, diabetes medications, and birth control pills), so one should consult a pharmacist or physician before using it.

Tryptophan and Serotonin:

Tryptophan is an amino acid that serves as a precursor for both serotonin and melatonin.

Serotonin is a compound that promotes feelings of safety and relaxation, which are conducive to sleep. However, while it helps people get to sleep and reduces sleep disturbances, it also counteracts acetylcholine and is a suppressor of REM sleep. A serotonin deficiency can result in sleep disturbance, as well as anxiety, depression, and overeating.

You can obtain tryptophan, which helps the brain produce serotonin, from eating carbohydrates, especially whole grain oats, brown rice, corn and quinoa. Turkey, nuts, and seeds are also good sources of tryptophan. Serotonin itself can be obtained from some dietary sources, such as walnuts, pineapples, bananas, kiwis, plums, and tomatoes.


In summary, there are several nonprescription sleep aids available, through over-the-counter supplements and through food sources. Anticholinergics are probably not a good choice due to recently discovered risks, whereas supplements such as melatonin and valerian have some promise, depending on what other medications a person is taking.

For Further Reading:

Bauer, B. (2016). Is melatonin a helpful sleep aid — and what should I know about melatonin side effects? Published online by the Mayo Clinic on November 11, 2014. Retrieved online August 2, 2016 at:

Biala, D. (2015). Food sources of acetylcholine. Published online by Livestrong, January 18, 2015. Retrieved online August 2, 2016 from:

Buchanan, K., M. Petrovic, S. Chamberlain, N. Marrion, and J. Mellor. (2010). Facilitation of long-term potentiation by muscarinic M(1) receptors is mediated by inhibition of SK channels. Neuron. 2010 Dec 9;68(5):948-63.  doi: 10.1016/j.neuron.2010.11.018.

Gray, S., M. Anderson, S. Dublin, J. Hanlon, R. Hubbard, R. Walker, O. Yu, P. Crane, and E. Larson. (2015). Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study. JAMA Intern Med. 175(3):401-407. doi:10.1001/jamainternmed.2014.7663.

Hall, R. (1998). Neurotransmitters and Sleep. Published online by Missouri University of Science & Technology. Retrieved online July 31, 2016, at:

Hasselmo, M. (2006). The Role of Acetylcholine in Learning and Memory. Curr Opin Neurobiol. 2006 Dec; 16(6): 710–715. doi: 10.1016/j.conb.2006.09.002

Huang, H-W, B-L Zheng, L. Jiang, Z-T Lin, G-B Zhang, L. Shen, and X-M Xi. (2015). Effect of oral melatonin and wearing earplugs and eye masks on nocturnal sleep in healthy subjects in a simulated intensive care unit environment: which might be a more promising strategy for ICU sleep deprivation? Critical Care 2015 19:124 doi: 10.1186/s13054-015-0842-8

O’Mahony, S., G. Clarke, Y. Borrea, T. Dinan, and J. Cryan. (2015). Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behavioural Brain Research 277 (2015) 32–48.

Vazquez, J., and H. Badhdoyan. (2001). Basal forebrain acetylcholine release during REM sleep is significantly greater than during waking. Am J Physiol Regul Integr Comp Physiol. 2001 Feb; 280(2):R598-601.

Winkler, J., S. Suhr, F. Gage, L. Thal, and L. Fisher. (1995). Essential role of neocortical acetylcholine in spatial memory. Nature. 1995 Jun 8;375(6531):484-7.

Nanoparticles and the industrial food supply

Nanotechnology is now commonplace in the food industry. Nanoparticles, measured in nanometers (or billionths of a meter) are fragments of substances that behave very differently at a tiny scale than they do in their normal, or macro, form. They are hundreds of times smaller than a red blood cell. That means they can go places in the body, and interact with cells, in different ways than do unprocessed foods.

Substantial evidence links nanoparticles with “leaky gut,” numerous autoimmune diseases, and other adverse health effects.

Nanoparticles are used for a variety of purposes in food processing and packaging. They can be used to purify water, to prevent caking in powdered substances, to form gelatin, to protect against UV light in packaging, to prevent the growth of bacteria, and to detect contamination.

One of the most commonly used nanoparticles is titanium dioxide (TiO2). This is used in toothpaste (to make it look whiter), sunscreen, and cosmetics. It is also used in many processed foods including mints, gum, coated candies, vitamins, frosting, pudding, creamers, cheese substitutes, and other items. Most Americans consume at least some TiO2 every day.

Health effects: Because nanoparticles can penetrate the body in ways that naturally occurring substances cannot, they interact with it and affect it in unintended ways. Known health effects of nanoparticles include:

  • Systemic genetic damage in mice, including single- and double-strand DNA breaks, chromosomal damage, and inflammation, all of which increase the risk for cancer.
  • Pathological lesions in the liver, spleen, kidneys, and brain, when introduced into the body through the lungs or gastrointestinal tracts.
  • Diseases associated with inhaled nanoparticles include asthma, bronchitis, emphysema, lung cancer, Parkinson’s and Alzheimer’s.
  • Nanoparticles in the gastrointestinal tract are linked to Crohn’s disease and colon cancer.
  • Nanoparticles that enter the circulatory system are implicated in arteriosclerosis, blood clots, arrhythmia, and heart disease.
  • In human cells as well as in the lungs of mice, nanoparticles have been found to transform the amino acid arginine into a molecule called citrulline. Citrulline is indicated in the development of autoimmune diseases, such as rheumatoid arthritis, lupus, and scleroderma.

Autoimmune disorders: The role of nanoparticles in the development of autoimmune diseases is particularly disturbing, and the mechanism is quite clear. The conversion of the amino acid arginine into citrulline causes human proteins that use this modified building block to become dysfunctional. The immune system targets these faulty (citrullinated) proteins and attacks its own tissues and organs, into which the faulty proteins are incorporated.

Leaky gut: Nanoparticles and other industrial food additives are also implicated in the development of “leaky gut,” or tight junction dysfunction. The tight junction (TJ) is comprised of a complex network of plaque proteins. This thin layer is responsible for preventing intestinal permeability. If the TJ stops working properly, the immune cells in the lamina propria (below the epithelium) will be exposed to a huge number of foreign antigens, causing an overreaction of the immune cells known as the autoimmune cascade.

Diet plays a critical role in determining the development of leaky gut. Emulsifiers, organic solvents, microbial transglutaminase, and nanoparticles have all been shown to increase intestinal permeability by breaching the integrity of the tight junction. Some beneficial  bacteria and probiotic strains can help reverse intestinal permeability, strengthening the tight junction.

Transglutaminase: Nanoparticles are used in the production of microbial transglutaminase (mTG), an enzyme widely used in food processing. Transglutaminase is an enzyme that helps proteins bond. Its cross-linking property is used to manufacture cheese, baked goods, and in meat processing (it is sometimes known as “meat glue”). It is used to increase the firmness, viscosity, elasticity and water-binding capacity of processed foods.

Because mTG makes proteins more stable, it makes them harder for the body to eliminate. It has also been found to increase intestinal permeability. This combination exposes gluten proteins (gliadens) in greater quantities to the immune cells in the epithelium, possibly helping to trigger celiac disease.

Additionally, the presence of antibodies to transglutaminase is a key diagnostic indicator of celiac disease, suggesting that the presence of unlabeled mTG in the food supply is not doing celiacs any favors.

In summary, the rise of industrial food additives such as nanoparticles and transglutaminase is probably not coincidental to the rise of autoimmune disorders. Better labeling is needed to make it possible for consumers to determine whether to avoid such ingredients.


For further reading:

Kieliszek, M., & Misiewicz, A. (2014). Microbial transglutaminase and its application in the food industry. A review. Folia Microbiologica59(3), 241–250.

Lerner, A., and T. Matthias. (2015). Food Industrial Microbial Transglutaminase in Celiac Disease: Treat or Trick. International Journal of Celiac Disease, 3(1): 1-6. doi: 10.12691/ijcd-3-1-10

Lerner, A., and T. Matthias. (2005). Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmune Review, 14(6): 479-89. doi:10.1016/j.autrev.2015.01.009.

Liu, Z., N. Li, and J. Neu. (2005). Tight junctions, leaky intestines, and pediatric diseases. Acta Paediatr 94(4): 386-93.

Mohamed, B.M., et al. (2012). Citrullination of proteins: a common post-translational modification pathway induced by different nanoparticles in vitro and in vivo. Nanomedicine 7(8): 1181-1195. doi:10.2217/nnm.11.177

Shi, H., R. Magaye, V. Castranova, and J. Zhao. (2013). Titanium dioxide nanoparticles: a review of current toxicological data. Particle and Fibre Toxicology 201310:15. doi: 10.1186/1743-8977-10-15

Ulluwishewa, D., et al. (2011). Regulation of Tight Junction Permeability by Intestinal Bacteria and Dietary Components. The Journal of Nutrition March 2011. doi: 10.3945/jn.110.135657.

Hidden Hormone Imposters

Strawberries in plastic containerThe human endocrine system is complicated and finely balanced. Too much of one hormone, not enough of another, and the results can be a lot worse than moodiness or bad skin. Cancers and other disorders have been linked to hormone imbalances, or “endocrine disruption.” Our bodies are sensitive to even small amounts of endocrine disrupting chemicals, which is why they are often measured in parts per trillion.

Endocrine disruptors, which can either mimic or block naturally occurring hormones, can be found in places you might not normally associate with hormones. Here are some examples of how you might be exposed in daily life.

Food containers: You can eat organic meat, dairy and produce until the cows come home, but if you use plastic containers containing BPA to hold your leftovers, lunches, or filtered water, you’re not doing yourself any favors. BPA, or bisphenol-A, is a known endocrine disruptor. It mimics estrogen in the body, and has been linked with cancer (especially breast cancer), reproductive problems, obesity, early puberty, heart disease, and liver failure.

Plastic water bottles are the primary source of BPA exposure for most people. Food cans are another common source, since many cans are lined with BPA. Plastic items with recycling label #7 often contain BPA. According to an NIH study (2009), BPA is found in the bodies of 93% of Americans – and it lingers in the body for days after exposure.

Soy: Some plants contain naturally occurring hormone analogs (chemicals that mimic hormones in chemical makeup and function). For example, soy contains genistein and daidzein, which are estrogen analogs. Phytoestrogens can actually have health benefits, depending on who you are. Some of these (which are similar to the benefits of estrogen) include reduced lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms. However, if you are a breast cancer patient, or a male, soy products may not be for you.

Herbicides: Atrazine is commonly used on corn crops, and people are exposed to it through consuming corn products and even drinking water, due to runoff from fields. This endocrine disruptor has been linked to breast cancer, delayed puberty, and prostate problems. To demonstrate how strongly atrazine disrupts hormones, note that even at low levels, it causes feminization of male frogs (male frogs go through a sex-change, becoming egg-laying females).

Pesticides: Organophosphate pesticides, one of the most commonly used classes of pesticides, have been linked in many studies to deficits in brain development, behavior and fertility. These endocrine disruptors interfere with the way testosterone communicates with cells, and exposure can reduce testosterone levels and cause thyroid problems.

In a 2011 study of 37 pesticides and fungicides commonly used on food crops, 30 were found to blocked or mimicked male hormones. Sixteen of the 30 had no previously known hormonal activity, indicating that the health effects of pesticides have yet to be thoroughly understood.

Of the tested compounds, those that blocked male hormones (androgens) most effectively included the insecticide fenitrothion, an organophosphate used on orchard fruits, grains, rice, vegetables and other crops. Other endocrine disruptors identified included the fungicides fludioxonil, fenhexamid, dimethomorph and imazalil. Fungicides, used on crops such as strawberries, are commonly found as residue in food, in part because they are applied close to harvest.

Scented Products: Most commercially produced products that have a scent (such as room fresheners, scented candles, even hand lotions and soaps) contain chemicals called phthalates. In addition to products containing the ingredient “fragrance,” phthalates are also found in plastic food containers and plastic wrap with the recycling label #3.

Pthalates trigger apoptosis, or cell death, in testicular cells. As endocrine disruptors, they also reduce sperm count and motility, are linked to birth defects in the male reproductive system, and are associated with obesity, diabetes, and thyroid problems.

Non-Stick Cookware: If you use non-stick pans for cooking, you are exposing yourself to PFCs, or perfluorinated chemicals. One of these compounds, PFOA, never biodegrades; once it has been produced, it stays in the environment forever. PFOA, an endocrine disruptor, has been linked with poor sperm quality, low birth weight, kidney disease, thyroid disease, and high cholesterol. It is believed to act by altering steroid hormone production and affecting ovarian function.

How Endocrine Disruptors Work: Endocrine disruptors can function in any of several ways.

  • They can mimic naturally occurring hormones (causing the body to behave as if it has too much of a particular hormone).
  • They can block naturally occurring hormones from binding to receptors, by “docking” there themselves (causing the body to behave as if it has a deficit of a particular hormone).
  • Or they can interfere with or block the way hormones are produced, controlled, or broken down in the body (causing a response completely different than would occur with undisrupted hormones).

Given the serious effects of endocrine disruptors, it may be worth your while to eliminate as many as possible. For example, avoid plastic bottles and food containers, and stick with organic produce (avoiding herbicides and pesticides).




For further reading:

Biello, D. (2009). Like a Guest That Won’t Leave, BPA Lingers in the Human Body. Scientific American. Published online January 28, 2009 at

Cone, M. (2011). New tests reveal many pesticides block male hormones. Environmental Health News. Published online at

Environmental Working Group. (2013). Dirty Dozen Endocrine Disruptors: 12 Hormone-Altering Chemicals and How to Avoid Them. Published online October 28, 2013 at

National Institute of Health Sciences. (2015). Endocrine Disruptors. Published online at

Orton, F., et al. (2011). Widely Used Pesticides with Previously Unknown Endocrine Activity Revealed as in Vitro Antiandrogens. Environ Health Perspect. 2011 June; 119(6): 794–800. doi: 10.1289/ehp.1002895.

Patisaul, H., and W. Jefferson. (2010). The pros and cons of phytoestrogens. Frontiers in Neuroendocrinology, 31(4), pp. 400-419.

White, S., S. Fenton, and E. Hines. (2011). Endocrine disrupting properties of perfluorooctanoic acid. J Steroid Biochem Mol Biol. 2011 Oct;127(1-2):16-26. doi: 10.1016/j.jsbmb.2011.03.011.

Sugar Substitutes, Obesity, and Diabetes

Sweetened DrinkRecent studies have found that well-meaning efforts to avoid the dangers of sugar can backfire. In fact, several common sugar substitutes: saccharin, sucralose, and aspartame, have been linked with glucose intolerance and weight gain.

How does this happen? Some 80% of the human immune system resides within the gut, in the form of the “microbiome,” the diverse colony of friendly and essential bacteria that accompany us throughout our lives. But if the microbiome is disturbed, it can become unhealthy, leading to autoimmune disorders and, apparently glucose intolerance.

Artificial sweeteners, especially saccharin, have been found to cause dysbiosis, or an unhealthy imbalance of gut bacteria. This, in turn, leads to glucose intolerance (a precursor of diabetes), as well as weight gain. This was found to be true not only in mice that were fed artificial sweeteners, but in mice that received bacterial transplants from the special-diet mice.

It also held true in humans. In a small study, more than half of the healthy human subjects who added artificial sweeteners to their diets developed glucose intolerance in less than a week. A larger-scale study of about 400 people found a correlation between metabolic syndrome (including glucose intolerance and weight gain) and consumption of artificial sweeteners.

In addition to this new research on the microbiome, there are reasons not to use certain artificial sweeteners dating back to the 1980s. Aspartame, for example, has been linked with some fairly serious neurological disorders.

Are there any “safe” sugar substitutes? To date, stevia has not been linked with dysbiosis, cancer, or neurological symptoms; and it does not raise blood sugar. People who are allergic to chrysanthemums are more likely to be allergic to stevia. It is relatively new to the market, so not all the evidence is in, but at this point it looks like one of the best bets if you must avoid sugar.




For further reading:

Abbott, A. (2014). Sugar substitutes linked to obesity: Artificial sweetener seems to change gut microbiome. Nature News. Posted September 17, 2014.

Collins, F. (2014). Taking a New Look at Artificial Sweeteners. NIH Director’s Blog. Posted October 7, 2014.

Farley, A. (2013). Symptoms of Aspartame Poisoning. Posted August 16, 2013.

Lalonde, B. (2013). Known Side Effects of Stevia. Posted October 21, 2013.

Roberts, H.J. (1988). Reactions attributed to aspartame-containing products: 551 cases. Journal of Applied Nutrition, 40: 85-94, 1988. See summary of reactions here:

Suez, J., et al. (2014). Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514, 181–186 (09 October 2014). doi:10.1038/nature13793.

The Inheritance of Fear

Fearful MouseRecent research reveals some surprising new insights into what can be inherited. It turns out that fear, or at least fearful behavior, can be passed down by the control of gene expression. This is a very different matter than transmitting a behavior or attitude to the next generation through teaching or observation. Rather than being learned, the fear is transmitted epigenetically.

In a study published in 2014, researchers used electric shock to condition mice to be fearful of the scent of acetophenone (a benign, fruity odor that would not normally trigger fear). The mice exhibited fearful behavior (trembling, cowering) in the presence of the smell, even once the electric shock had been withdrawn, showing that their fear was now a learned behavior.

What was remarkable about this experiment was not the learned fear, but the fact that the fear response was passed on to their offspring for at least two generations. The children and grandchildren of these mice, although they had never been shocked, showed similar trembling and cowering when they smelled acetophenone.

Although one might suspect that this could be transmitted by changes in maternal behavior if the mother was fearful, this was not the case; the fear response was passed down even by male mice.

Not only was the behavioral response passed down, but both the parent mice and their descendants showed changes in their brain structures related to the receptors for acetophenone, and in the area of the brain involved in processing fear. This inheritance was mediated by epigenetic factors (the marking of which genes are turned on or off).

This greatly broadens our understanding of what can be inherited, and what we can pass down to our children. If epigenetic inheritance happens in a similar way in humans, this means that our fears are not just our own baggage, but can burden our descendants as well.


For further reading:

Dias, B. and K. Ressler. (2014). Parental olfactory experience influences behavior and neural structure in subsequent generations. Nature Neuroscience 17, 89–96 (2014) doi:10.1038/nn.3594

Smythies, J., L. Edelstein and V. Ramachandran. (2014). Molecular mechanisms for the inheritance of acquired characteristics – exosomes, microRNA shuttling, fear and stress: Lamarck resurrected? Frontiers in Genetics. 5: Article 133. 3pp. doi:10.3389/fgene.2014.00133.

Meat and Early Puberty

Cheerful Small Indian Girl Isolated on WhiteDo you have a pre-adolescent daughter? If so, you might think carefully about the amount and origin of the meat you feed her.

Today’s factory-farmed meat is full of synthetic hormones (80-90% of feedlot cattle are administered growth-enhancing hormones, including estrogens, androgens, and progestins). The androgens include steroids such as melengestrol acetate, zeranol, testosterone propionate, and trenbolone acetate; the estrogens include estradiol. To give you an idea of how disruptive these chemicals can be, the runoff of feedlot steroids into streams has been linked with fish in those streams changing sex (male fish being feminized into female fish).

Why is this relevant to girls? Meat consumption has been directly linked with early onset puberty in girls, particularly in the U.S., which consumes more meat per capita than any other nation (see map: The age of puberty has been dropping as meat consumption has increased over time – and particularly since factory farming was introduced in the 1980s.

In 1950, a British study benchmarked the earliest puberty for girls at 11.5 years. By 1997, a U.S. study found that the earliest signs of puberty had fallen to 9.9 years among white girls and 8.9 years among African-American girls. A Danish study found that puberty onset dropped by a year between 1991 and 2006, from 10.8 years to 9.8 years.

A direct link between the amount of meat in the diet and early puberty was found in a 2010 study. About half the girls eating more than 12 portions of meat a week at the age of seven started their periods by age 12 ½, compared with only 35% of those who ate fewer than four portions of meat weekly. The more meat they ate, the earlier they tended to reach puberty.

Early onset puberty is associated with an increased risk for hormonally-related cancers. The National Cancer Institute identifies a risk factor for breast cancer as “an early age at first menstrual period” (before age 12). It is also associated with increased mortality rate. A 2009 CDC study found that women with ovarian cancer are 51% more likely to die of it if they entered puberty before age 12 than if they entered puberty at age 14 or older.

A plant-based diet is one option for concerned parents. Another option is organic meat, which does not carry the risks associated with synthetic hormones.



For further reading:

Hutchins, S. (2007). Assessing Potential for Ground and Surface Water Impacts from Hormones in CAFOs. Presentation by the Ground Water & Ecosystems Restoration Division of the Environmental Protection Agency at the EPA Office of Research & Development CAFO workshop in Chicago, Illinois, August 21, 2007.

Hylton, W. (2015). A Bug in the System: Why last night’s chicken made you sick. The New Yorker, February 2, 2015.

Kolpin, D.W. et al. (2002). Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999-2000: A national reconnaissance. Environ. Sci. Technol. 36(6): 1202-1211. doi/pdf/10.1021/es011055j

Neill, F. (2010). Puberty Blues. Intelligent Life Magazine, June 29, 2010.

Raloff, J. (2002). Hormones: Here’s the Beef: environmental concerns reemerge over steroids given to livestock. Science News. 161(1): January 5, 2002, p10.

Robbins, C. et al. (2009). Influence of Reproductive Factors on Mortality after Epithelial Ovarian Cancer Diagnosis. Cancer Epidemiol Biomarkers Prev. July. 18: 2035. doi: 10.1158/1055-9965.EPI-09-0156.

Rogers, I. et al. (2010). Diet throughout childhood and age at menarche in a contemporary cohort of British girls. Public Health Nutrition. 13: 2052-2063. doi: 10.1017/S1368980010001461.

Vajda, A. et al. (2008). Reproductive Disruption in Fish Downstream from an Estrogenic Wastewater Effluent. Environ. Sci. Technol. 42 (9): 3407–3414.