Shorts

briefed by Jule Klotter

Acupuncture

and

PTSD

Clinical and animal studies indicate that acupuncture is a helpful adjuvant therapy for several mental conditions, including anxiety and depression; but evidence for its value in treating PTSD is still meager, according to a Korean review article led by Young-Dae Kim. The Korean researchers used four randomized controlled trials and two uncontrolled clinical trials. Five studies involved earthquake victims in China. The sixth, which the reviewers assessed as having the highest quality, was a randomized controlled US pilot study.

The US study, led by Michael Hollifield, MD, at the University of Louisville’s School of Medicine (Kentucky), involved 84 patients with a PTSD diagnosis and a Posttraumatic Symptom Scale-Self Report (PSS-SR) score of ≥16 (upper moderate range; above 20 is severe). Seventy of the 84 (83%) were dealing with traumatic events that had occurred before age 17; 28 of them (33%) experienced at least five years of abuse as children. Patients were randomly assigned to one of three groups: acupuncture, cognitive behavioral therapy, or a wait list that acted as a control. Trauma-focused cognitive behavioral therapy (CBT) is one of the main treatments for the nervousness and avoidance behavior that comes with reexperiencing past traumas. Patients in the acupuncture and CBT groups received 2 hours of standardized therapy per week plus at least 15 minutes/day of home-based therapy. Home-based therapy for the acupuncture group consisted of massaging Vaccaria seeds taped to acupuncture points in the ear.

Mean PSS-SR score for the acupuncture group dropped from 31.2 at baseline to 14.3 at treatment’s end, which was comparable to the CBT group (32.0 at baseline to 17.5 at treatment’s end). The wait-list control group showed no significant change. “By the end of treatment 68% (13 of 19 people) in the acupuncture group, 43% (9 of 21 people) in the CBT group, and 19% (4 of 21 people) in the WLC group had PSS-SR scores below the entry criterion level of ≥16,” say the authors. At the three-month follow-up, 68% of the acupuncture group remained below a PSS-SR score of 16. The percentage of CBT patients below 16 had increased from 43% to 62% (13 of 21).

A 2012 case study, written by licensed acupuncturist Greg Golden, describes the use of auricular acupuncture to treat combat-related PTSD in a 60-year-old Vietnam veteran. Golden used the NADA protocol that inserts acupuncture needles into five specific points on the ears: Sympathetic, Shen Men, Kidney, Liver, and Lung. The NADA protocol is used as an adjuvant treatment for detoxification programs. Its reported effects include “improved retention in drug treatment programs; more optimistic attitudes about detoxification and recovery; reductions in cravings and anxiety; fewer episodes of sleep disturbance; and reduced need for pharmaceuticals,” according to Acupuncture Today.

Golden’s patient reported 11 PTSD-related symptoms: chronic fatigue/lack of energy, chronic pelvic pain, depression/grief, general anxiety, headaches, insomnia, irritability/anger issues, nightmares, panic attacks, skin rashes, and stomach/intestinal problems. The patient received 7 consecutive weekly treatments, beginning November 11, 2010, and an additional 11 treatments as needed through his final treatment on May 12, 2011. During a follow-up phone consult about seven months after the last treatment, the patient reported complete resolution of 5 of the initial 11 symptoms (fatigue, anxiety, insomnia, panic attacks, and skin problems) and noticeable improvement in another 4 symptoms (depression, headaches, anger issues, nightmares). The chronic pelvic pain and stomach/intestinal problems did not respond to acupuncture. Walter Reed Veterans Administration Hospital (Washington, D.C.) offers the NADA protocol to veterans, their families, and their caregivers at no charge, according to Golden.

Golden G. The lasting effects of using auricular acupuncture to treat combat-related PTSD: a case study. American Acupuncturist. Summer 2012. Available at Alt-HealthWatch database. Accessed September 7, 2013.

Hollifield M, Sinclair-Lian, N, Warner TD, Hammerschlag R. Acupuncture for Posttraumatic Stress Disorder. J Nerv Ment Dis. June 2007:195(6):504–513. Available at www.phoenixhealth.me/Acupuncture%20pdf/Acupuncture%20for%20Posttraumatic%20Stress%20Disorder.pdf. Accessed September 13, 2013.

Kim YD, Heo I, Shin BC, Crawford C, Kang HW, Lim JH. Acupuncture for posttraumatic stress disorder: a systematic review of randomized controlled trials and prospective clinical trials. Evid Based Complement Altern Med. 2013. Available at http://dx.doi.org/10.1155/2013/615857. Accessed September 13, 2013.

The NADA Protocol [Web page]. Acupuncture Today. www.acupuncturetoday.com/abc/nadaprotocol.php. Accessed September 13, 2013.

ADHD Overdiagnosis in Boys

Boys are more likely to be treated for attention deficit/hyperactivity disorder (ADHD) than girls. Multiple ADHD clinical samples have a male-to-female ratio between 5:1 and 9:1, according to Katrin Bruchmüller et al. The rationale for this wide disparity has been that girls are being underdiagnosed. Girls with ADHD tend to be inattentive, rather than impulsive and disruptive, so they are easily overlooked. However, two recent studies present evidence that boys are being overdiagnosed.

Swiss researcher Katrin Bruchmüller and German colleagues Jürgen Margraf and Silvia Schneider investigated the role of bias in ADHD diagnosis. They hypothesized that some therapists rely on their perception of ADHD rather than following the specific Diagnostic and Statistical Manual of Mental Disorders (4th ed.: DSM-IV) and/or International Classification of Diseases (10th rev.: ICD-10) diagnosis criteria. To test their hypothesis, Bruchmüller and colleagues constructed and pretested four different case vignettes based on DSM-IV and ICD-10, which have identical criteria. The first vignette clearly met DSM-IV and ICD-10 criteria for an ADHD (combined type) diagnosis. The second vignette matched the first except it noted a failure to met Criteria b (onset before age 7) and c (impairment in two or more settings). In addition to lacking Criteria b and c, Vignette three reported fewer than the required six symptoms of inattention and six symptoms of hyperactivity/impulsivity. The fourth vignette met the diagnostic criteria for generalized anxiety disorder, which has some of the same symptoms as ADHD. “To test whether the gender of the youth influenced the therapists’ diagnostic decision, we formulated all four vignettes in boy and girl versions,” say the authors. “The boy was named Leon and the girl was named Lea. All other information in the vignettes was identical.”

Each of the eight vignettes, along with a cover letter and questionnaire, was sent to 125 German therapists, who specialized in children and adolescents. One reminder letter was mailed to therapists who did not respond within six weeks. A total of 473 therapists out of 1000 responded. (The authors were aiming for a 40% response rate: 400.)

After excluding the therapists who refused to make a diagnosis without more information, the authors found that 8 out of 98 (8.2%) therapists who received Vignette 1 gave a diagnosis other than ADHD (false negative diagnoses). In contrast, 57 of 285 (20%) of the non-ADHD vignettes (Vignettes 2–4) received an ADHD diagnosis (false positive diagnoses). When they analyzed false negative and false positive diagnoses for girls separately, the authors found “no significant difference between the proportion of false positive (11.3%) and false negative (7.5%) diagnoses.” In comparison, 21.8% of the boy Vignettes 2–4 were falsely diagnosed with ADHD. Only 6.6% of boys with the ADHD Vignette 1 were given a false negative diagnosis. The significantly higher rate of false positive diagnoses compared with false negatives indicates an overdiagnosis of ADHD in boys. Overdiagnosis means unnecessary treatment.

A 2012 Canadian study, led by Richard L. Morrow, focused on another factor that contributes to ADHD overdiagnosis: the relative age of children. The researchers looked at the health records of 937,943 school children, age 6 to 12 years, living in British Columbia. A December 31 birth date is the cut-off for entry into kindergarten or first grade. Consequently, children born in December can be several months younger than their classmates. Morrow and colleagues found that “ … boys born in December were 41% more likely, and girls 77% more likely, to have a prescription for a medication to treat ADHD than their peers born in January.” The study, like two earlier US studies, indicates that being among the youngest and least mature children in a classroom increases their risk of being diagnosed with ADHD and receiving treatment. “Inappropriate diagnosis of ADHD in a child born late in the year might lead parents and teachers to treat the child differently or adversely change the child’s self-perceptions,” they write. In addition, ADHD medications can adversely affect sleep, appetite, growth, and cardiovascular health. “Our analyses add weight to concerns about the medicalization of the normal range of childhood behaviours,” say Morrow and colleagues, “particularly for boys.”

Bruchmüller K, Margraf J, Schneider S. Is ADHD diagnosed in accord with diagnostic criteria? overdiagnosis and influence of client gender on diagnosis. J Consult Clin Psychol. 2012:80(1);128–138. Available at www.kli.psy.ruhr-uni-bochum.de. Accessed September 13, 2013.

Morrow RL, Garland EJ, Wright JM, Maclure M, Taylor S, Dormuth CR. Influence of relative age on diagnosis and treatment of attention-deficit/hyperactivity disorder in children (early release version). CMAJ. March 5, 2012. Available at www.cmaj.ca/content/early/2012/03/05/cmaj.111619.full.pdf+html. Accessed September 13, 2013.

Cherries for Gout

Eating cherries decreases the risk of recurrent gout attacks, according to a 2012 study. Gout (painful inflammation that usually affects the big toe, midfoot, or ankle) is caused by monosodium urate crystals. The crystals form when serum urate levels exceed saturation concentrations (6.8 mg/dL or 0.41 mmol/L). If urate levels remain too high, acute gout flares become more frequent and joint damage can result. Icing the painful joint and NSAIDS are the usual treatment for acute gout flares. Xanthine oxidase inhibitors, such as allopurinol, are usually prescribed for people who have more than one gout attack per year or who display joint damage. These drugs lower serum urate levels. Food that worsen gout include high-purine foods such as organ meats and seafood; alcohol (especially beer); and fructose-containing beverages, according to Nicola Dalbeth. Vitamin C and cherries decrease the risk of recurrent gout; both decrease serum urate, according to Gelber and Solomon.

Researchers at Boston University initiated an ongoing case-crossover study to investigate risk factors for recurrent gout attacks in February 2003. Yuqing Zhang, DSc, and colleagues used data from this study to assess the effect of cherry intake. They followed, via the Internet, 633 people with a physician diagnosis of gout for one year. Participants reported date and symptoms of gout attacks, their use of medications, exposures to risk factors, and daily servings of cherries and cherry extract during the 2-day period before an attack and gave the same information during control periods. A single serving consists of one-half cup, about 10 to 12 cherries.

Eating about three servings of cherries within a two-day period was associated with a 35% decreased risk of having a gout attack. Eating more than three servings was not as beneficial. Participants who consumed cherry extract alone had a 45% lower gout attack risk compared with periods when they did not consume cherry extract. “The effect of cherry intake on the risk of recurrent gout attacks tended to be stronger when cherries or cherry extract were consumed during periods of higher purine intake or alcohol abstention, and when diuretics or NSAIDs were not used,” say the researchers. In addition, cherries appear to have a synergistic effect with allopurinol; participants who took allopurinol and ate cherries had a 75% lower gout attack risk compared with periods when they took neither. It will be interesting to see if these benefits can be produced in an intervention study.

Dalbeth N. Management of gout: from lifestyle to pharmacotherapy. Rheumatol Pract News. November 2012;4–8. Available at www.rheumatologypracticenews.com. Accessed September 25, 2013.

Gelber AC, Solomon DH. If life serves up a bowl of cherries, and gout attacks are “the pits”: implications for therapy. Arthritis Rheum. December 2012:64(12);3827–3830.

Zhang Y, Neogi T, Chen, C, Chaisson C, Hunter DJ, Choi HK. Cherry Consumption and Decreased Risk of Recurrent Gout Attacks. Arthritis Rheum. December 2012;64(12):4004–4011.

Confidence, Risk, and Testosterone

Financial traders’ testosterone and cortisol levels affect confidence and risk preferences, according to research led by neuroscientist John M. Coates. With permission of a London trading floor, Coates and J. Herbert enlisted 17 male traders, ages 18 to 38 (mean 27.6 years). For eight consecutive business days, participants gave a saliva sample to check hormone levels and recorded their profit and loss (P&L) each morning at 11 a.m. and again at 4 p.m. (before and after most of the day’s trading). At day’s end, they also completed a questionnaire to monitor food, drinks, medications, or personal news received during the day that might affect endocrine response. If a morning testosterone level was higher than the trader’s median level, the trader increased his profit by day’s end. Coates and Herbert also found that a trader’s cortisol levels rose with market volatility and with variations in his trading results; cortisol rose “ … in some cases by as much as 500 per cent,” according to a 2010 review article.

In the 2010 review article, Coates, Mark Gurnell, and Zoltan Sarnyai connected medical research on steroid hormones to financial traders’ behaviors. The steroid hormones – cortisol, testosterone, and estradiol – regulate brain neural function in areas that relate to economic decision-making (e.g., prefrontal cortex and hippocampus) and to emotional response (e.g., amygdala). Testosterone (produced primarily in the testes but also by the adrenal cortex and ovaries) increases vigilance, visual-motor skills, search persistence, and confidence. Animal and human studies indicate that testosterone relates to competition and risk-taking. All of these qualities are useful in financial trading.

Successful outcomes during competitions increase testosterone levels. Numerous animal and human studies have found that testosterone surges before a competition (athletic or not). Winners experience a further increase in testosterone, while the hormone drops significantly in losers. These levels can persist for weeks. With higher testosterone comes the benefits of confidence, vigilance, increased visual-motor skills, and so on – qualities that give competitors an advantage. But too much testosterone can also produce detrimental risk-taking, impulsivity, and sensation seeking. The boom can go bust as financial traders take irrational risks.

Cortisol, a stress biomarker, climbs when people and animals face uncertainty. Coates et al. explain that lab animals subjected to electric shocks can maintain normal cortisol levels if the shocks occur at regular intervals and are preceded by a warning sound, but their cortisol levels rise as the shocks become increasingly haphazard. A moderate amount of cortisol improves performance. However, “extended periods of uncertainty and uncontrollable stress can promote a condition known as ‘learned helplessness’, in which persons, and animals, lose all belief in their ability to control or influence their environment,” say the authors. In contrast to high testosterone that produces irrational risk-taking, high cortisol provokes an unwillingness to take any risks.

“Market stability is served by opinion diversity,” say Coates et al., “so it may be served as well by having more [hormonal] balance in the banks between young and old, men and women. One does not need to argue that one group is better than others for this policy to work; merely different.”

Coates JM, Gurnell M, Sarnyai Z. From molecule to market: steroid hormones and financial risk-taking. Phil Trans R Soc B. (2010); 365:331–343. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC2827458/pdf/rst620090193.pdf. Accessed September 13, 2013.

Coates JM, Herbert J. Endogenous steroids and financial risk taking on a London trading floor. PNAS. April 22, 2008; 105(16):6167–6172. Available at www.ncbi.nlm.nih.gov/pmc/articles/PMC2329689. Accessed September 13, 2013.

Hormones, Body Composition,

and

Sexual Function in Men

A team of Massachusetts researchers, led by Joel S. Finkelstein, MD, found that estrogen as well as testosterone affects men’s body composition and sexual function. The researchers gave 400 healthy men, ages 20 to 50 years old, goserelin acetate to suppress their production of testosterone. When testosterone production decreases, estradiol levels also decline; over 80% of estradiol in men is derived from testosterone. In order to track testosterone’s effects, the researchers randomly assigned 198 of the 400 men a placebo gel or one of four concentrations of testosterone gel (1.25 grams, 2.5 grams, 5 grams, or 10 grams) to apply daily for 16 weeks. The remaining 202 men received anastrozole in addition to a placebo or testosterone gel. Anastrozole inhibits the conversion of testosterone to estradiol. Every four weeks, the participants gave blood samples to assess hormone levels and completed questionnaires regarding physical function, health status, vitality, and sexual function. At baseline and 16 weeks, researchers used dual-energy X-ray absorptiometry to assess body fat and lean muscle, computed tomography to a assess subcutaneous- and intra-abdominal-fat areas and thigh-muscle, and leg press to assess lower-extremity strength.

Changes in body fat and lean muscle were the primary outcomes. The results indicate that testosterone promotes lean muscle mass, and estradiol prevents body fat. Men receiving placebo gel in both cohorts showed a significant decrease in lean muscle mass. The men in cohort 1 who were getting 1.25 g/day of testosterone also showed a decline in lean muscle, whereas the men in the estradiol-inhibited group taking 1.25 g did not. The percentage of body fat increased significantly in all estradiol-inhibited participants. Only men receiving 10 g/day of testosterone gel without the estradiol inhibitor showed a decrease in the percentage of body fat. Men in the first cohort who received less than 10 grams of testosterone per day (and, therefore, produced less estradiol than the 10 g receivers) showed an increase in body fat percentage that mirrored the estradiol-inhibited group: “Subcutaneous-fat area increased by a factor of 2 to 3 in men receiving 1 g, 1.25 g, or 2.5 g of testosterone daily, as compared with men receiving 5 g or 10 g daily, though only the comparisons with the 10-g dose group were significant.”

The authors state: “In the groups that received testosterone, inhibition of estrogen synthesis (cohort 2), as compared with intact estrogen synthesis (cohort 1), was associated with significant increases in the percentage of body fat (P<0.001), subcutaneous-fat area (P<0.001), and intraabdominal-fat area (P=0.002) and with significant decreases in sexual desire (P<0.001) and erectile function (P=0.022); these findings provide additional evidence of an independent effect of estradiol on these measures.”

In addition to showing that estradiol affects male body composition and sexual desire and function, this study also questions the current definition of low testosterone, currently defined as “at least 2 SD below the mean value for healthy young adults.” “Although convenient, this classification fails to consider the physiological consequences of specific testosterone levels,” say the authors. They suggest using a mean serum level of about 200 ng/dl as the point at which to provide testosterone supplementation. Lean mass, muscle strength, and erectile function remained stable as long as testosterone levels were ≥200 ng per deciliter in most, but not all, participants. Practitioners need to adjust serum target levels according to an individual’s functional outcome. Given estradiol’s role in male body composition and sexual function, the researchers suggest using aromatizable androgens, which can convert to estradiol, when supplementing instead of nonaromatizable androgens.

Finkelstein et al. state: “Our finding that estrogens have a fundamental role in the regulation of body fat and sexual function, coupled with evidence from prior studies of the crucial role of estrogen in bone metabolism, indicates that estrogen deficiency is largely responsible for some of the key consequences of male hypogonadism and suggests that measuring estradiol might be helpful in assessing the risk of sexual dysfunction, bone loss, or fat accumulation in men with hypogonadism.”

Finkelstein JS, Lee H, Burnett-Bowie S-A M, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. September 12, 2013;369(11):1011–1022.

Inner Conflict of War Veterans

About one-third of war veterans who seek counseling for posttraumatic stress disorder (PTSD) suffer from moral injury. These vets do not have terrifying flashbacks of life-threatening events, nor are they stricken with grief over the loss of a buddy, which accounts for another one-third of PTSD. Moral injury, also called “inner conflict” by the Marine Corps, arises when a soldier performs an action, or witnesses or fails to prevent an event that violates his/her moral code. “A moral injury tortures the conscience; symptoms include deep shame, guilt and rage,” according to Associated Press journalist Pauline Jelinek. “‘You may not have actually done something wrong by the law of war, but by your own humanity you feel that it’s wrong,’” retired Col. Elspeth Ritchie, chief clinical officer at the District of Columbia’s Department of Mental Health, told Jelinek.

People with moral injury exhibit some typical PTSD symptoms, such as avoidance and numbing; but, according to a framework proposed by Brett Litz, PhD and colleagues, moral injury is primarily characterized by shame, guilt, demoralization, self-sabotage, and self-harm. These patients do not have the anxiety and hyperarousal seen in those with typical PTSD. Forgiveness, specifically self-forgiveness, helps dissipate the inner conflicts and guilt. An intervention called Adaptive Disclosure uses exercises such as having an imagined conversation with the deceased or with “a compassionate and forgiving moral authority” to resolve inner conflict.

“‘Human beings aren’t just turn-on, turn-off switches,’ Veterans of Foreign Wars spokesman Joe Davis [told Jelinek], noting that moral injury is just a different name for a familiar military problem. ‘You’re raised on “Thou shalt not kill,” but you do it for self-preservation or for your buddies.’”

Jelinek P. Veterans suffer “moral injury” from war. Spartanburg Herald-Journal. February 23, 2013. Available at http://bigstory.ap.org/article/im-monster-veterans-alone-their-guilt. Accessed September 13, 2013.

Maguen S, Litz B. Moral injury in veterans of war. PTSD Res Q. 2012;23(1):1–6. Available at www.ptsd.va.gov. Accessed September 13, 2013.

Overdiagnosis

“Medicine’s much hailed ability to help the sick is fast becoming challenged by its propensity to harm the healthy,” say Roy Moynihan, Jenny Doust, and David Henry in a British Medical Journal article. “ … Narrowly defined, overdiagnosis occurs when people without symptoms are diagnosed with a disease that ultimately will not cause them to experience symptoms or early death.” Overdiagnosis causes unnecessary anxiety and stress to basically healthy people and their loved ones as well as burdening them with the costs of further tests and treatments – interventions that may jeopardize their health. The problem of overdiagnosis has gained international attention.

Several factors are fueling the overdiagnosis epidemic. Screening technology improvements are making it possible to find increasingly small “abnormalities,” many of which never cause symptoms or contribute to death. “It is becoming clearer that a substantial proportion of these earlier ‘abnormalities’ will never progress, raising awkward questions about exactly when to use diagnostic labels and therapeutic approaches traditionally deployed against much more serious forms of disease,” say Moynihan and colleagues. Companies that make and sell these tests and treatments have tremendous influence on medical care. To promote their products, companies fund disease awareness campaigns, medical education, and research foundations, and advertise directly to consumers. More sales mean more profit. Hospitals, clinics, and practitioners also financially benefit from widespread screening programs. Doctors and patients have long followed the belief that it’s better to treat than to wait and see, but treatment often has its own risks. At this point, tests cannot always tell whether an abnormality is life threatening and should be treated or not.

In addition to technology, parameters that define a disease are expanded to include more people. “As definitions broaden and thresholds fall, people with smaller risks or milder problems are labeled,” say the authors, “which means the potential benefits of treatment decline, raising the possibility that harms will outweigh benefits.” Being “at risk” is too often treated as if the disease is actually present. Once again, financial gain has had a role: “ … the members of panels that write disease definitions or treatment thresholds often have financial ties to companies that stand to gain from expanded markets.” Moynihan and colleagues call for a policy change that would bar people with conflicts of interest from being on such panels.

“An intuitive belief in early detection, fed by deep faith in medical technology is arguably at the heart of the problem of overdiagnosis,” the authors write. While appropriate medical care can be lifesaving, patients and practitioners need to be educated about the harms that come with believing “more is better.” BMJ plans to publish an article series that focuses on overdiagnosis of specific conditions such as ADHD, asthma, bipolar disease, cholesterol, chronic kidney disease, depression, high blood pressure, melanoma, osteoporosis, prostate cancer, and type 2 diabetes. Consumer Reports is working on lay-friendly summary versions. BMJ and Consumer Reports joined Dartmouth Institute for Health Policy and Clinical Practice (Hanover, New Hampshire) and Bond University (Robina, Queensland, Australia) to host the first international scientific conference called “Preventing Overdiagnosis” on September 10–12, 2013. The 2014 conference takes place at Oxford University in the United Kingdom on September 15–17. More information about overdiagnosis is available at http://www.preventingoverdiagnosis.net and http://consumerhealthchoices.org.

Moynihan R, Doust J, Henry D. Preventing overdiagnosis: how to stop harming the healthy. BMJ. May 29,2012; 344:e3502. Available at www.ncbi.nlm.nih.gov/pubmed/22645185. Accessed September 24, 2013.

Winding back the harms of too much medicine [Web page]. Consumer Health Choices. http://consumerhealthchoices.org/campaigns/preventing-overdiagnosis. Accessed September 13, 2013.

Answers to Critics of the 2012 Séralini GM Study

The 2012 publication of “Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize” received an onslaught of criticism and accusations of “pseudoscience” from those affiliated with GM crop productions. The rat study, led by French biochemist and molecular biologist Gilles-Eric Séralini, investigated the effects of lifelong consumption (2 years) of genetically modified NK603 maize (corn) and the Roundup pesticide formula used on it. Herbicide safety studies have focused solely on glyphosate, the active ingredient in Roundup. In actual practice, glyphosate-based pesticides such as Roundup include adjuvants that enhance glyphosate’s effect. The Séralini study is the first long-term study on this crop. The Monsanto safety assurance study, conducted by B. Hammond (2004), lasted 13 weeks.

The 2012 Séralini study randomly assigned by weight 100 male rats and 100 female rats into groups of 10. The control group ate standard feed made from non-GM maize with the closest possible DNA to NK603 and plain water. Three groups ate Roundup-tolerant NK603 that was treated with Roundup; the GM maize made up 11%, 22%, or 33% of the rats’ diet. Another three groups also ate NK603 as 11%, 22%, or 33% of their diet, but this maize was not treated with Roundup. Rats in the last three groups ate the control standard non-GM diet and Roundup (R) was added to their drinking water in one of three concentrations: “1.1 X 10^-8% of R (0.1 ppb of R or 50 ng/L of glyphosate, the contaminating level of some regular tap waters), 0.09% of R (400 mg/kg, US [maximal residual level] of glyphosate in some GM feed) and 0.5% of R (2.25 g/L, half of the minimal agricultural working dilution).” The GM maize and the pesticide were associated with kidney deficiency in both male and female rats. Both treatments also affected sex hormonal balance. Treated males exhibited liver congestions and necrosis 2.5 to 5.5 times higher to controls. Males also had four times more large tumors than controls. Treated females developed more and larger mammary tumors than controls: “In females, all treated groups died 2-3 times more than controls, and more rapidly.”

In their 2012 response to criticism about the study’s design, Séralini et al. emphasized that they followed the Organization for Economic Co-operation and Development (OECD) guideline for testing and the 2004 Hammond safety study (which also used OECD guidelines) as the basis for their design. In addition to lasting longer than the Hammond study, the Séralini study looked at three dietary levels of GM food, while the Hammond study used only two. OECD recommends using three. It is impossible to track unusual dose-response patterns, such as caused by endocrine disruptors, using only two. Also, Séralini et al. used the same breed of rat (Sprague Dawley) and biochemically measured the same number of rats per sex as Hammond’s Monsanto study in accordance with OECD guidelines for chronic toxicity testing. Critics attributed the high number of large tumors to the rats’ breed; Sprague Dawley rats are known to be susceptible to cancer. Séralini and colleagues point out that Sprague Dawley rats are “preferentially used by some agencies such as for the National Toxicology Program … for 2-year carcinogenicity and other long-term studies.” Moreover, the breed’s propensity to develop cancer does not explain the severity and number of tumors found in treated animals compared to controls.

Critics also disputed the nonlinear dose-response effect caused by the different Roundup concentrations: the highest dose did not produce the greatest toxicity or mortality. Séralini et al. point out that U-, inverted U-, or J-shaped response curves are often produced by environmental toxins that have endocrine-disrupting effects. In response to critics’ claim that glyphosate has shown no endocrine-disrupting effects in safety studies, Séralini et al. state, “The results of the study presented here clearly demonstrate that lower levels of complete agricultural glyphosate herbicide formulations, at concentrations well below officially set safety limits, induce severe hormone-dependent mammary, hepatic and kidney disturbances.” (my emphasis) Farmers use glyphosate-based formulas, not glyphosate alone, on crops.

The reported safety of pesticide-resistant GM crops is based on short-term, manufacturer-funded, safety trials, such as the one conducted by Hammond and colleagues, and on the assumption that GM crops do not significantly differ from non-GM crops. The biotech industry is not monitoring farm animals or humans for adverse effects. Séralini and colleagues say, “[The NK603 maize and Roundup study] is the most detailed test conducted to date that is also independent from biotechnology and pesticide companies. We encourage others to replicate such chronic experiments, with greater statistical power. What is now urgently required is for the burden of proof to be obtained experimentally by studies conducted independent from industry. … ”

Séralini GE, Clair E, Mesnage R, et al. Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize. Food Chem Toxicol. 2012;50:4221–4231. Available at http://dx.doi.org/10.1016/j.fct.2012.08.005. Accessed September 13, 2013.

Séralini GE, Mesnage R, Defarge N, et al. Answers to critics: Why there is a long term toxicity due to a Roundup-tolerant genetically modified maize and to a Roundup herbicide. Food Chem Toxicol. 2012 (in press). Available at http://dx.doi.org/10.1016/j.fct.2012.10.57. Accessed September 13, 2013.