A new study suggests that reports of the impending infertility of the human male are greatly exaggerated.
- A new review of a famous study on declining sperm counts finds several flaws.
- The old report makes unfounded assumptions, has faulty data, and tends toward panic.
- The new report does not rule out that sperm counts are going down, only that this could be quite normal.
Several years ago, a meta-analysis of studies on human fertility came out warning us about the declining sperm counts of Western men. It was widely shared, and its findings were featured on the covers of popular magazines. Indeed, its findings were alarming: a nearly 60 percent decline in sperm per milliliter since 1973 with no end in sight. It was only a matter of time, the authors argued, until men were firing blanks, literally.
Well… never mind.
It turns out that the impending demise of humanity was greatly exaggerated. As the predicted infertility wave crashed upon us, there was neither a great rush of men to fertility clinics nor a sudden dearth of new babies. The only discussions about population decline focus on urbanization and the fact that people choose not to have kids rather than not being able to have them.
Now, a new analysis of the 2017 study says that lower sperm counts is nothing to be surprised by. Published in Human Fertility, its authors point to flaws in the original paper's data and interpretation. They suggest a better and smarter reanalysis.
Counting tiny things is difficult
The original 2017 report analyzed 185 studies on 43,000 men and their reproductive health. Its findings were clear: "a significant decline in sperm counts… between 1973 and 2011, driven by a 50-60 percent decline among men unselected by fertility from North America, Europe, Australia and New Zealand."
However, the new analysis points out flaws in the data. As many as a third of the men in the studies were of unknown age, an important factor in reproductive health. In 45 percent of cases, the year of the sample collection was unknown- a big detail to miss in a study measuring change over time. The quality controls and conditions for sample collection and analysis vary widely from study to study, which likely influenced the measured sperm counts in the samples.
Another study from 2013 also points out that the methods for determining sperm count were only standardized in the 1980s, which occurred after some of the data points were collected for the original study. It is entirely possible that the early studies gave inaccurately high sperm counts.
This is not to say that the 2017 paper is entirely useless; it had a much more rigorous methodology than previous studies on the subject, which also claimed to identify a decline in sperm counts. However, the original study had more problems.
Garbage in, garbage out
Predictable as always, the media went crazy. Discussions of the decline of masculinity took off, both in mainstream and less-than-reputable forums; concerns about the imagined feminizing traits of soy products continued to increase; and the authors of the original study were called upon to discuss the findings themselves in a number of articles.
However, as this new review points out, some of the findings of that meta-analysis are debatable at best. For example, the 2017 report suggests that "declining mean [sperm count] implies that an increasing proportion of men have sperm counts below any given threshold for sub-fertility or infertility," despite little empirical evidence that this is the case.
The WHO offers a large range for what it considers to be a healthy sperm count, from 15 to 250 million sperm per milliliter. The benefits to fertility above a count of 40 million are seen as minimal, and the original study found a mean sperm concentration of 47 million sperm per milliliter.
Healthy sperm, healthy man?
The claim that sperm count is evidence of larger health problems is also scrutinized in this new article. While it is true that many major health problems can impact reproductive health, there is little evidence that it is the "canary in the coal mine" for overall well-being. A number of studies suggest that any relation between lifestyle choices and this part of reproductive health is limited at best.
Lastly, ideas that environmental factors could be at play have been debunked since 2017. While the original paper considered the idea that pollutants, especially from plastics, could be at fault, it is now known that this kind of pollution is worse in the parts of the world that the original paper observed higher sperm counts in (i.e., non-Western nations).
There never was a male fertility crisis
The authors of the new review do not deny that some measurements are showing lower sperm counts, but they do question the claim that this is catastrophic or part of a larger pathological issue. They propose a new interpretation of the data. Dubbed the "Sperm Count Biovariability hypothesis," it is summarized as:
"Sperm count varies within a wide range, much of which can be considered non-pathological and species-typical. Above a critical threshold, more is not necessarily an indicator of better health or higher probability of fertility relative to less. Sperm count varies across bodies, ecologies, and time periods. Knowledge about the relationship between individual and population sperm count and life-historical and ecological factors is critical to interpreting trends in average sperm counts and their relationships to human health and fertility."
Still, the authors note that lower sperm counts "could decline due to negative environmental exposures, or that this may carry implications for men's health and fertility."
However, they disagree that the decline in absolute sperm count is necessarily a bad sign for men's health and fertility. We aren't at civilization ending catastrophe just yet.
An early feasibility study finds a potential new treatment for Alzheimer's disease.
For the past few years, Annabelle Singer and her collaborators have been using flickering lights and sound to treat mouse models of Alzheimer's disease, and they've seen some dramatic results.
Now they have results from the first human feasibility study of the flicker treatment, and they're promising.
"We looked at safety, tolerance, and adherence, and several different biological outcomes, and the results were excellent—better than we expected," says Singer, assistant professor in the biomedical engineering department at Georgia Institute of Technology and Emory University.
Singer shared preliminary results of the feasibility study in October at the American Neurological Association annual meeting. Now she is a corresponding author with Emory neurology researcher James Lah of a paper outlining their findings in the journal Alzheimer's & Dementia: Translational Research & Clinical Interventions.
The flicker treatment stimulates gamma waves, manipulating neural activity, recruiting the brain's immune system, and clearing pathogens—in short, waging a successful fight against a progressive disease that still has no cure.
Previous research already had shown that sensory areas in the human brain will entrain to flickering stimuli for seconds to hours. But this was the first time Singer and her team were able to test gamma sensory stimulation over an extended period of time.
The study included 10 patients with Alzheimer's-associated mild cognitive impairment, which required them to wear an experimental visor and headphones that exposed one group to light and sound at 40 hertz for an hour a day over eight weeks, and another group for four weeks after a delayed start.
"We were able to tune the devices to a level of light and sound that was not only tolerable, but it also successfully provoked an underlying brain response," Lah says.
As they hoped and expected, Singer says, "there was widespread entrainment." That is, brain activity—in this case, gamma waves—synchronized to the external stimulation.
Gamma waves are associated with high-level cognitive functions, like perception and memory. Disruptions to these waves have been found in various neurological disorders, not just Alzheimer's.
The human feasibility study showed that the gamma flicker treatment was safe and tolerable. And perhaps most surprising, patients followed the full treatment schedule.
"Adherence was one of our major concerns," Singer says. "When we sent the device home with the participants, would they use it? Would they use it for a couple of days, and that would be it? We were pleasantly surprised that this wasn't the case."
Adherence rates hovered around 90%, with no severe adverse effects reported during the study or the 10-month open label extension (some patients even volunteered to continue being monitored and assessed after the study, though this data wasn't part of the published research).
Some participants reported mild discomfort that could have been flicker related—dizziness, ringing in the ears, and headaches. But overall, Singer says, the device's safety profile was excellent. She also reported some positive biological outcomes.
"We looked at default mode network connectivity, which is basically how different brain regions that are particularly active during wakeful rest and memory, interact with each other," Singer says.
"There are deficits in this network in Alzheimer's, but after eight weeks [of treatment], we found strengthening in that connectivity." This may indicate stronger interactions and therefore better communication between these regions.
In previous animal studies, the 40Hz of flicker stimulated mouse gamma waves, significantly reducing some Alzheimer's pathogenic hallmarks and recruited microglia to the cause—these are the primary immune cells in the brain. But in the human study, there were no clear changes in the presence of pathogens amyloid beta or p-Tau.
However, as with the mouse studies, "we are getting immune engagement in humans," Singer says. The flicker treatment sparked the activity of cytokines, proteins used in cell signaling—a sign that flicker had engaged the brain's immune system.
"That is something we want to see, because microglia do things like clear out pathogens. Some people think that part of what's going wrong in Alzheimer's is a failure of this clearance mechanism," Singer says.
She and Lah have wondered if a longer human trial would make a difference—would there be reduced amyloid activity, for example.
"So far, this is very preliminary, and we're nowhere close to drawing conclusions about the clinical benefit of this treatment," Lah says. "But we now have some very good arguments for a larger, longer study with more people."
Funding for the study came from the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, the Packard Foundation, the Friends and Alumni of Georgia Tech, the Lane Family, the Wright Family, and Cognito Therapeutics. Any findings, conclusions, and recommendations are those of the researchers and not necessarily of the sponsors.
Annabelle Singer owns shares in Cognito Therapeutics, which funded the human study at Emory Brain Health Center. Cognito aims to develop gamma stimulation-related products. These conflicts are managed by Georgia Tech's Office of Research Integrity Assurance.
Source: Georgia Tech
Original Study DOI: 10.1002/trc2.12178
The treatment is here, but are we ready?
- Ketamine is the first hallucinogen approved for therapeutic use in the U.S.
- Research has shown ketamine is effective at treating depression.
- Though ketamine infusion therapy is now being offered at hundreds of North American clinics, there are unaddressed dangers in the current ketamine gold rush.
In March 2019, the FDA approved ketamine, under the trade name Spravato (esketamine), for clinical use in treatment-resistant depression therapy. Alongside racemic ketamine, which is commonly used in ketamine infusion therapy, ketamine is the first hallucinogen approved for therapeutic usage in the United States.
Technically, ketamine is not a psychedelic but rather a hallucinogen and dissociative. (While ketamine has psychedelic effects, traditional psychedelics bind to the 5-HT2B receptor.) Still, advocates for psychedelic therapy recognize ketamine as a gateway for traditional psychedelics, such as psilocybin and LSD, to be considered for therapeutic usage.
To understand the proliferation of ketamine clinics across North America, the origins of this peculiar substance — one that went from battlefields to veterinary clinics to dance clubs in the span of two decades — must be discussed.
History of ketamine
In 1962, chemistry professor Calvin Stevens synthesized ketamine while researching alpha-hydroxyimine rearrangements. The first human tests were conducted on prisoners in 1964. Ketamine soon replaced phencyclidine (PCP) as the go-to anesthetic in hospitals. It was initially used on soldiers during the Vietnam War following FDA approval in 1970. Thanks to its success on the battlefield, ketamine was placed on the World Health Organization's List of Essential Medicines.
Ketamine has been used broadly as a sedative and anesthetic; to aid in emergency surgeries in war zones; as a bronchodilator for severe asthmatics; to treat certain types of seizures; and in postoperative pain management. Now, ketamine infusions and nasal sprays are being used for depression. Ketamine is also showing potential efficacy in treating chronic pain and suicidal ideation, though more research needs to be done.
Of all of those uses, ketamine has predominantly been used as an anesthetic in humans and animals. While it restricts breathing less than other similar medications, ketamine also produces hallucinations (thus, it's labeled as a dissociative anesthetic). The list of potential side effects from using ketamine is long, including nausea, double vision, breathing problems, impaired memory, liver enzyme abnormalities, urinary tract problems, and even increased depression — an alarming possibility given its growing use as an antidepressant replacement.
Small-scale studies on using ketamine to treat depression were conducted in 2000 and 2006. Further research confirmed its role in alleviating depressive symptoms, including the possibility that the antidepressant effects of a single dose can persist for weeks. In 2016, the FDA fast-tracked ketamine trials for depression.
A chair is seen in a therapy room at Field Trip, a psychedelic therapy clinic in Toronto, Ontario, Canada.Credit: Cole Burston/AFP via Getty Images
Ketamine infusion therapy
There has yet to be a consensus on how ketamine addresses depression. Antidepressants act on the body's serotonin and noradrenaline systems. Ketamine seems to interfere with an amino acid derivative, NMDA. As a 2017 study published in the journal Nature explains:
"Ketamine is responsible for blocking the N-methyl-D-aspartate (NMDA) receptor, which causes an immediate alleviation of depressive effects, while another metabolite in the drug helps the effects last for hours. This blockage is also what causes the hallucinogenic effects."
Small intravenous doses of esketamine — an enantiomer of ketamine and the substance actually approved by the FDA — seem to lift depressed patients out of their funk. So does Spravato, a nasal spray that can only be administered under supervision in a doctor's office or clinic.
Patients that have tried two different antidepressant medications with no success (the definition of treatment-resistant depression) can legally receive ketamine infusions or Spravato at clinics located all over the country. Since the therapy is generally not covered by insurance, treatments range from $300 to $2,000 per session; the Field Trip Treatment Program, which includes psychotherapy and six infusions, runs $4,700.
The process of ketamine infusion therapy is varied depending on which clinic you attend. Companies like Field Trip and organizations such as MAPS require psychotherapy sessions to coincide with infusions.
Unfortunately, therapeutic implementation has not always lived up to federal requirements. Reports of patients quitting antidepressants and psychotherapy to use esketamine as their primary source of treatment abound. Since medical professionals with no mental health training, such as nurse practitioners, anesthesiologists, and pain physicians, can legally administer ketamine, patients are left to process the drug's effects with little to no guidance.
Thus far, efficacy has been mixed. As STAT News editor Megan Thielking writes, people with minor depressive issues are likely better candidates for ketamine therapy than those with treatment-resistant depression, the very cohort the drug is purported to target.
"Studies vary but have found response rates to ketamine as high as 70 percent among people with major depression who have failed a few other antidepressants. But the rate is lower for patients with extremely treatment-resistant depression, and how long any improvement lasts varies from one patient to the next."
Was ketamine approved too quickly?
While ketamine therapy is certainly promising, the FDA-approved trials raise a number of red flags. A recent analysis in The British Journal of Psychiatry concludes that we're moving too fast. Author Mark Horowitz writes:
"Out of the three short-term trials conducted by Janssen only one showed a statistically significant difference between esketamine and placebo. These were even shorter than the 6-8 week trials the FDA usually requires for drug licensing."
Trials usually last three months; the approved ketamine trials only lasted four weeks and barely showed efficacy above placebo. More concerning, the FDA allowed Janssen to submit a discontinuation trial with a study design flaw as evidence of efficacy — side effects were treated as evidence of relapse, not withdrawal symptoms. Even more alarmingly, six people in the esketamine group died during the trials, including three by suicide, two of which had previously shown no signs of suicidal ideation.
When Janssen stated that the problem wasn't esketamine but underlying conditions, the FDA accepted the reasoning even though no conclusive evidence was provided. This doesn't mean ketamine therapy isn't potentially therapeutic, though it does suggest that its approval by the FDA was rushed.
Psychiatrist Lori Calabrese, who offers ketamine infusion for depression and anxiety in her clinic, puts it best when stating, "The pace of ketamine treatment in real-world practices has outstripped what researchers are able to do and publish." Time will tell if this treatment proves more beneficial than dangerous in mental health treatments.
Stay in touch with Derek on Twitter and Facebook. His most recent book is "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."
The way you speak might reveal a lot about you, such as your willingness to engage in casual sex.
- A new study finds a deeper voice is associated with self-reported extraversion, dominance, and casual sex.
- It was the first study on the topic to objectively measure voice pitch.
- The authors suggest that hormones like testosterone might explain their findings.
We make snap decisions about other people based on information that we can gather quickly. One of the many ways that we do this is by making bold conclusions about other people's personalities based on their voices alone. Various studies demonstrate that people associate a deep voice with dominance, but those with higher pitched voices are perceived as nervous or neurotic. Popular culture seems to agree with and reinforce these stereotypes.
Are these perceptions accurate? Maybe. A new study by an international team of researchers with the goal of more accurately determining what our voices reveal about us has demonstrated that there is some connection between how we sound and who we think we are.
The voice-personality connection
Lead author Dr. Julia Stern of the University of Göttingen explained:
"Even if we just hear someone's voice without any visual clues — for instance on the phone — we know pretty soon whether we're talking to a man, a woman, a child, or an older person. We can pick up on whether the person sounds interested, friendly, sad, nervous, or whether they have an attractive voice. We also start to make assumptions about trust and dominance. The first step was to investigate whether voices are, indeed, related to people's personality."
The study included data from 2,000 people from four countries involved in eleven previous independent studies focused on other questions. Each of these studies involved some kind of self-reporting of personality traits and vocal recordings. The recordings were analyzed with Praat, software that determined the frequencies of the participants' speaking voices.
The study is the largest ever conducted on the topic and the first to use an objective measure of pitch rather than subjective rankings such as "high pitched" or "deep." Each participant's vocal pitch was then compared to the self-reported personality data they provided.
The findings associated self-reported levels of dominant tendencies, extroversion, and increased interest in and acceptance of sociosexuality (casual sex or sex outside of a relationship) with a lower pitched voice. This was true for men and women of any age. The findings were in line with the previous, less robust studies on the subject.
Other stereotypes, like if a higher pitched voice hints at neuroticism, openness to new experiences, or agreeableness, were impossible to determine with the data at hand.
Voice isn't everything
It should be remembered that the personality traits that this study associates with vocal pitch are self-reported, so there are some serious limitations. For instance, it is entirely possible that vocal pitch is associated with thinking you're extroverted when you actually aren't. Furthermore, all four countries in the study are WEIRD, so the findings probably cannot be universalized.
Additionally, there are plenty of examples of people for whom the voice-personality link doesn't apply. For example, Teddy Roosevelt, an extremely extroverted, dominating man, had a fairly high pitched voice.
The authors do speculate that there could be a connection between testosterone levels in men, their vocal pitch, and their perceived level of dominance that would be supported by previous studies. However, they have no hypothesis explaining why that same relationship exists for women.
The authors suggest that further studies in this area could focus on finding a possible physical connection between these traits and vocal pitch and to determine if they hold for traits which are not self-reported.
Who needs steroids when you have the placebo effect?
- A study suggests that the effectiveness of sports drinks may depend in part on their color.
- Runners who rinsed with a pink liquid ran better than those who consumed the same but colorless drink.
- Improvement in their performance is likely due to a placebo effect.
The "placebo effect" is real. It's the name for a strange phenomenon that most notably occurs during clinical trials. People who are given an inactive substance, like a sugar pill, often experience the same therapeutic benefit as those who are given actual medicine. It's not their imagination — it really happens. (Even better, recent research suggests that therapeutic benefits occur even when the person knows that they were given a placebo.)
Now, a new study from the University of Westminster (UOW) Centre for Nutraceuticals in London and published in Frontiers in Nutrition suggests that the placebo effect may explain yet another phenomenon: Athletic performance.
The research showed that treadmill runners who rinsed their mouths with a pink liquid increased their performance over runners who swished with exactly the same liquid but without the coloring. Why pink? The color is generally linked to sweetness, and the researchers wondered if that association would subconsciously trick the runners into an expectation of more carbohydrates and thus energy.
Author Sanjoy Deb explains:
"The influence of color on athletic performance has received interest previously, from its effect on a sportsperson's kit to its impact on testosterone and muscular power. Similarly, the role of color in gastronomy has received widespread interest, with research published on how visual cues or color can affect subsequent flavor perception when eating and drinking."
Running for science
Credit: Ryan De Hamer / Unsplash
For the study, the researchers recruited ten healthy adults — six men, four women. All were regular exercisers, with an average age of 30. The participants were told that they would be testing the relative benefits of two commercial sports drinks after watching a brief video explaining the value of such beverages. Previous research found that mid-exercise rinsing with such drinks can reduce the perceived intensity of exercise.
The drinks consisted of 0.12 grams of sucralose dissolved in 500 mL of plain water — an artificially sweetened rinse low in calories. The liquids contained no other additives common to sports drinks such as caffeine. The pink version had non-caloric coloring added but was otherwise identical.
After a 12-minute warmup phase of jogging followed by running, the athletes ran at a difficult pace for 30 minutes, rinsing with their drinks as they ran. Following a brief cool-down, they were interviewed to capture their impressions of the exercise session. (Each runner tested both drinks.)
The researchers found that when the volunteers used the pink rinse, they ran an average of 212 meters farther and 4.4 percent faster. They also enjoyed the exercise more.
Deb said, "The findings from our study combine the art of gastronomy with performance nutrition, as adding a pink colorant to an artificially sweetened solution not only enhanced the perception of sweetness, but also enhanced feelings of pleasure, self-selected running speed, and distance covered during a run."
The researchers also plan to dig deeper into the phenomenon by investigating the possibility that the pinkness of the beverage is somehow directly activating the brain's reward areas.