Does drinking coffee reduce the risk of atrial fibrillation? Maybe just a little.

Atrial fibrillation is the most common type of heart arrhythmia in the U.S. and Europe, affecting millions of people every day. A-fib is a condition where your heart beats irregularly and less efficiently than normal. Some people experience a-fib without even being aware of it, but it is a serious condition that leads to an estimated 750,000 hospitalizations per year in the U.S. alone.

The causes of a-fib are not completely understood, but one widespread view is that too much caffeine might trigger it. For example, the American Heart Association’s website says that “Avoiding atrial fibrillation and subsequently lowering your stroke risk can be as simple as foregoing your morning cup of coffee.” Although the site goes on to describe more substantial treatments such as beta blockers and calcium channel blockers, the idea of simply cutting out coffee seems very appealing.

As appealing as it sounds, this advice is wrong, at least for men.

In a study published in 2019 in the Journal of the American Heart Association, Vijaykumar Bodar and colleagues at Harvard Medical School looked at data from nearly 19,000 men who participated in the long-term Physicians’ Health Study. They looked at the risk of atrial fibrillation in men drinking anywhere from no coffee at all to 4 or more cups per day.

They found, somewhat surprisingly, that men who drank 1-3 cups of coffee per day had a 15% lower risk of a-fib compared to men who never or almost never drank coffee. They also found a small hint of a “dosage” effect, with the greatest reduction in risk at about 1.5 cups per day, and less benefit as consumption rose to 4 or more cups.

In a commentary published along with the study, Ryan Aleong and Amneet Sandhu point out that coffee contains a number of ingredients that might explain its cardiovascular benefits. They also point out, though, that the benefits are modest at best.

Unfortunately for women, though, coffee doesn’t seem to have the same benefits for them. Back in 2010, the Women’s Health Study reported that higher caffeine consumption did not increase the risk of a-fib in women, but it didn’t decrease it either. In a subgroup of women drinking the highest amount of coffee, they reported a slight increase in the risk of a-fib, but those women also smoked more often.

(Actually, if you look closely at the numbers in Table 2 of the Women’s Health Study report, women in the group who consumed an average amount of caffeine had a 20% lower risk of atrial fibrillation, consistent with the more recent study in men.)

For those of us who like coffee, this seems to be good news. At worst, coffee isn’t bad for heart health, and at best it might slightly reduce the risk of atrial fibrillation.

Some caveats: although these are large studies with thousands of men and women followed for many years, they rely on self-reporting of coffee consumption, which isn’t perfect. That’s probably the best we can do, though, since it’s impractical to measure caffeine consumption precisely over a long period of time.

The best advice, then, appears to be to keep drinking one or two cups of coffee per day, if you enjoy it. For those who have atrial fibrillation, cutting out that morning coffee, as the American Heart Association suggests, is very unlikely to help.

Why the "Lab Leak" Hypothesis Doesn’t Mean the COVID-19 Virus was Engineered

The “lab leak” hypothesis about the origin of Covid-19 has been getting a lot of attention lately, and deservedly so. This is the idea that the SARS-CoV-2 virus accidentally escaped from a laboratory in Wuhan, China, that conducts research on coronaviruses. Just a few weeks ago, a group of highly respected virologists and epidemiologists published a letter in the journal Science calling for a more thorough investigation, stating that the lab leak hypothesis was not taken seriously enough in earlier investigations.

The coincidence of having a major virus research facility, the Wuhan Institute of Virology (WIV), just a short distance from the live animal food market that was originally believed to be the source of the outbreak is too great to ignore. Even more curious is that WIV was actively doing research on coronaviruses in bats, including the bats that carry a strain of SARS-CoV-2 that is the closest known relative to the Covid-19 virus itself.

From the beginning of the outbreak, attention was focused on WIV, and various conspiracy theorists suggested, without any evidence, that the Covid-19 virus was either intentionally engineered, intentionally released, or both. Let me just say right off the bat that I don’t believe either of those claims.

However, I do think the lab leak hypothesis is credible, and it’s also possible that “gain of function” research (more about this below) might be responsible.

In arguing against (unsupported) claims that the Chinese released the virus on purpose, a group of virologists published a paper very early in the pandemic, in March 2020, which looked at the genome sequence of the virus and concluded that “SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.” Other studies since then have come to similar conclusions: the virus is very similar to naturally-occurring coronaviruses, and it is possible that it simply evolved naturally in the wild, probably in bats.

Even so, the lab leak hypothesis remains highly credible, regardless of whether or not the virus was genetically engineered. Here’s why. First, we know that lab accidents can happen and viruses can escape, even if these accidents are rare. We also know that the Wuhan Institute of Virology had thousands of viruses, including coronaviruses, in its facility. And despite claims that viruses couldn’t possibly have escaped accidentally, a 2017 Nature article describing the then-new Wuhan Institute reported, perhaps prophetically, that “worries surround the [Wuhan Institute of Virology], too. The SARS virus has escaped from high-level containment facilities in Beijing multiple times.”

The secrecy of the Chinese government, which has not yet allowed independent, outside scientists full access to WIV to investigate, hasn’t helped matters. We need to know if any viruses in WIV are similar to the Covid-19 virus, and at this point we can’t trust the Chinese government’s assurances on this question. Of course, even if they allow outsiders to investigate now, we cannot know that they have preserved all the viruses that were present in the lab in the winter of 2019-2020.

Now let’s talk about gain-of-function research. Gain of function, or GoF, refers to research that tries to make viruses or bacteria more harmful, by making them more infectious. This seems crazy, right? And yet it’s been going on for years, despite the efforts of many scientists to stop it. In the past, GoF research focused on the influenza virus, and in particular on a small number of scientists (highly irresponsible ones, in my view) who were trying to give avian influenza–bird flu–the ability to jump from birds into humans. I wrote about this in 2013, and in 2017, and again in 2019, each time calling on the US government to stop funding this extremely dangerous work. The NIH did put a “pause” on gain-of-function research for a few years, but the work resumed in 2019.

Now, let me explain why GoF research does not require artificially engineering a virus. Viruses mutate very rapidly all by themselves, and RNA viruses like influenza and SARS-CoV-2 mutate even more rapidly than DNA viruses. So a GoF experiment doesn’t need to engineer a virus to make it more infectious: instead, scientists can simply grow a few trillion viral particles, which is easy, and design experiments to select the ones that are more infectious. For example, some GoF research on bird flu simply sprays an aerosol mixture of viruses into a ferret’s nose (influenza research often uses ferrets, since you can’t ethically do this with people), and waits to see if the ferret comes down with the flu. If it does (and this has been done, successfully), the strain that succeeds now has a new function, because it can infect mammals. The viruses that are artificially selected (as opposed to natural selection) in these experiments will appear completely natural; no genetic engineering required.

We know that WIV was conducting gain-of-function experiments, and we know that its work included coronaviruses. Was the Wuhan Institute of Virology running GoF experiments on SARS-CoV-2 viruses from bats? Possibly. And if it was, these experiments could easily have produced a strain that infected humans. If a lab employee was accidentally infected with such a strain, that could have started the pandemic. And even if SARS-CoV-2 wasn’t the subject of GoF experiments, a naturally-occurring strain being studied at WIV could still have infected one of their scientists and thereby leaked out into the population.

I’m not saying that any of these events is likely. I am, however, agreeing with the scientists who, in their recent letter to Science, called for a deeper investigation into the cause of the Covid-19 pandemic.

Finally, let me echo a sentiment they expressed in their letter, which is best said by simply quoting them: “in this time of unfortunate anti-Asian sentiment in some countries, we note that at the beginning of the pandemic, it was Chinese doctors, scientists, journalists, and citizens who shared with the world crucial information about the spread of the virus—often at great personal cost.” Rather than seeking to cast blame, we need to uncover the origin of the Covid-19 pandemic, and any behaviors that led to it, as a means to help all societies prevent future pandemics. 

Patenting the Covid-19 vaccine is wrong

The world has recorded at least 166 million cases of Covid-19 and over 3.4 million deaths, according to the Hopkins coronavirus dashboard, and the true numbers are certainly far higher. The only way we will defeat this virus is through vaccines, and fortunately science has delivered the goods, with multiple highly-effective vaccines now being produced. In some countries we are turning the corner: in the U.S. cases have been steadily declining since mid-winter, and are now at their lowest level since last June.

Unfortunately, in many countries the virus is raging unchecked, and vaccines are in very short supply. We won't defeat SARS-CoV-2 until the whole world has adequate supplies of vaccines.

One barrier to wider, more rapid distribution of vaccines is patents. The companies that are making the vaccines have patents on them, which means that no one else can manufacture the vaccines without paying license fees. 

The human species doesn't have time for this nonsense. The profits of a few companies are far, far less important than the lives of millions of people. And yet many governments, including most EU countries, are standing firm behind the patent system. Crudely put, they are defending money over human lives. 

Recently, in a surprising move, President Biden announced support for a "vaccine waiver" that would allow any country to develop vaccines against Covid-19 without licensing the technology from one of the companies that currently holds a patent. The UK is now considering supporting a waiver as well, but other countries in the European Union and the G20 have come out against any waivers. The EU position seems to be that if you can't pay, you can't have the vaccine, even if your own scientists have the expertise to manufacture it themselves.

I've been an outspoken critic of patents for many years, including gene patents (which never should have been allowed in the first place) and software patents (which are frequently filed for trivial ideas and often used primarily to create lawsuits), but patents on the Covid-19 vaccine are objectionable for a different reason: they're unethical. If companies persist in enforcing them, the governments that approved the patents should simply invalidate them.

I know that many people will tell me I'm naive for suggesting this. I have heard their arguments before, many times. These include claims that without the patent system, companies simply won't invest in new inventions, and the public will suffer. These claims are, bluntly put, wrong.

In a famous 1955 interview, Jonas Salk, the inventor of the polio vaccine, was asked by journalist Edward Murrow who owned the patent. 

“Well, the people, I would say," Salk replied. "There is no patent. Could you patent the sun?" 

And yet despite not being patented, the polio vaccine was successfully produced and distributed, and as a result humans have essentially eliminated polio from the world. (It still persists in a handful of countries, due to political and economic reasons as well as vaccine resistance.)

Just a few days ago, epidemiologists Gregg Gonsalves and Gavin Yamey (from Yale and Duke) published a public call for a "people's vaccine," which would require waiving patent rights on Covid-19 vaccines. They point out that vaccine waivers are just one step among several that we need to take, as a species, if humans are going to defeat this pandemic. So if I'm naive, I guess I'm in good company.

Why do we have the patent system at all? When you think about it, the patent system is a government-supported, guaranteed monopoly on a commercial product. The only possible reason for governments to support this is that the citizens of their countries will benefit. The patent system was never designed to guarantee the profits of private corporations and law firms–but of course these groups have profited immensely from patents, and they have created an entire ecosystem to defend the status quo.

But I digress. The Covid-19 pandemic is a worldwide health crisis that surpasses anything we've seen since the 1918 influenza pandemic. Stopping the pandemic, and ending the suffering and death of millions of people, will require getting vaccines into most of the world's population, whether they live in rich countries or poor ones. Patents and the licensing fees that come with them can only slow down this process.

That's why enforcing patent protection on any Covid-19 vaccine is unethical. The companies that are claiming patents could fix this by announcing that they will offer their technology for free to anyone in the world, but we can't expect that to happen. President Biden's announcement that the U.S. supports a patent waiver, and the UK's likely announcement of a similar position in the coming days, are a great move in the right direction. Let's hope that the rest of the world's governments follow suit.

Should women be taking estrogen to treat the effects of menopause? New research says yes.

Until about 20 years ago, physicians routinely prescribed the hormones estrogen and progestin for women after menopause, when levels of both of these hormones decline. This seemed like a logical treatment, and the hope was that it would slow down bone loss (osteoporosis), reduce the risk of heart disease, and treat other age-related problems. Estrogen also has the benefit of increasing sexual desire for women.

This all came to a screeching halt in 2002, when the Women’s Health Initiative published its first findings about the effect of estrogen and progestin. Although the initial results did show benefits for osteoporosis, the main finding, trumpeted loudly at the time by NIH and in various press releases, was that the combination therapy (both hormones) increased the risk of breast cancer. As the US Office on Women’s Health says today on their website, the 2002 study found that “women taking combination (estrogen and progestin) hormone therapy for menopause symptoms had an increased risk for breast cancer, heart disease, stroke, blood clots, and urinary incontinence. Although women using combined hormone therapy had a lower risk of fractures and colorectal cancer, these benefits did not outweigh the risks.”

It turns out that this was not the full story.

As detailed in a stinging rebuke by one of the principal investigators of the Women’s Health Initiative, Robert Langer, the announcement in 2002 was deeply flawed, and many of the clinical investigators were “shocked” and “aghast” when they saw the paper announcing the results, which they had no opportunity to comment on before it appeared. Despite many objections, NIH proceeded with a “highly publicized press conference, centered around the inflammatory press release... that pandered to women’s greatest fear–the fear of breast cancer.”

Not surprisingly, the use of hormone replacement therapy plummeted after that, and has remained low since.

Perhaps even more striking, as Dr. Langer wrote in 2017, was that results from the Women’s Health Initiative (WHI) trial of estrogen alone (not in combination with progestin), reported 2 years later, suggested that estrogen alone led to a reduction in breast cancer, and a reduction in coronary heart disease as well.

So it appeared that, despite all its flaws and its premature termination, the WHI study showed that estrogen therapy alone seemed to have major benefits. The problems (if there were any–the termination of the study makes this conclusion somewhat uncertain) arose with a combination of estrogen+progestin.

Another large study of hormone therapy, the Danish Osteoporosis Prevention Study (DOPS), also halted its efforts after the 2002 report from the WHI. However, those women had already been in the study for 11 years at that point, and the Danish scientists continued to follow them for up to 16 years. They reported their findings in 2012, and the results were quite the opposite of what the WHI had found. I’ll just quote them because their findings are so stark:

“After 10 years of randomised treatment, women receiving hormone replacement therapy early after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction, without any apparent increase in risk of cancer, venous thromboembolism, or stroke.”

These benefits were confirmed in 2020, when a long-term followup of the women from the original WHI study found that women who took estrogen (CEE, or conjugated equine estrogen) only had lower rates of breast cancer than women who did not.

Even more recently, in a yet-unpublished preprint, NIH scientists Seo Baik and Clement McDonald examined the records of 1.5 million women collected from the Medicare database, looking for the effects of estrogen-only therapy on the risk of cancer, heart disease, and death. They found that the use of estrogen-only led to a 21% reduction in the risk of death, and a similar reduction in the risk of breast cancer, endometrial cancer, and ovarian cancer. Combination therapy using both estrogen and progestin, in contrast, led to an increased risk of breast cancer.

The message now seems pretty clear: despite the hasty, scary announcements made by the Women’s Health Initiative back in 2002, the accumulation of evidence suggests that estrogen-only hormone therapy for post-menopausal women is likely to convey a range of highly significant health benefits, not only for breast cancer, but also for osteoporosis and heart disease. The benefits vary by age, and by whether or not women have had hysterectomies, but the overly simplistic idea that hormone therapy causes breast cancer is simply wrong.

The NIH Office on Women’s Health still has this wrong, but the Women’s Health Initiative website is much more up-to-date, featuring an announcement from 2020 that describes the “enduring protective benefit of estrogen-alone therapy.”

As with most medical treatments, the true picture is complicated, but millions of women today might benefit from estrogen. If you think you might be one of them, talk to your physician.

Europe's pause on the AstraZeneca COVID vaccine plays right into anti-vaxxers' hands

Last week, more than a dozen European countries suspended the AstraZeneca Covid-19 vaccine. They claimed it was out of an excess of caution, but instead they played right into the hands of those who continue to spread anti-vaccine misinformation.

On Thursday, the European Medicines Agency announced that there was nothing to worry about, that the AstraZeneca vaccine was safe, and that all countries should resume using it.

Too late, I fear. The harm has already been done.

I’ve been fighting the anti-vax movement for years, as have many other scientists, doctors, and science bloggers. We’ve seen their strategies, and they don’t play fair. They don’t care about facts, and they love to scare people. This latest incident gives them plenty of fodder.

First let’s talk about the “fear” part. A very, very small number of cases were reported in which people had blood clots soon after getting the vaccine. This sounds scary.

But wait a minute. We are giving the vaccine to millions of people. If you look at a group that large, how many of them will have blood clots in a given week? The answer, not surprisingly, is greater than zero.

So the first thing that public health authorities should have asked is, obviously, are we seeing more blood clots than expected? But no, they didn’t do that. Instead, out of an excess of caution (so they claimed), they halted the AstraZeneca vaccine while they investigated. This meant that literally millions of vaccine doses were not administered.

Fortunately the investigation took only a few days. What did they find? Well, here’s the answer, directly from the European Medicines Agency itself:

“the number of thromboembolic events reported after vaccination ... was lower than that expected in the general population.”

In other words, the vaccine clearly doesn’t cause blood clots. If anything, it might even prevent blood clots, because the number observed was lower than expected. (No one is claiming that it actually prevents blood clots; I’m just pointing out how wrong the decision to halt the vaccine was.)

Now the unfounded fear of vaccine-induced blood clots has spread through Europe and beyond. You can’t “unsay” something like this, and anti-vax websites and social media groups are already using it to scare more people. (I won’t link to any of them because I don’t want to give them the traffic.) Indeed, several northern European countries still haven’t resumed use of the vaccine, and Germany, France, and Italy are including a warning (an incorrect one) that the vaccine might cause blood clots. This is just wrong.

Halting the AstraZeneca vaccine without doing some very basic number-checking was a huge blunder. Let’s just hope this decision doesn’t cost too many lives.

We've totally crushed the flu virus this year

 As awful as the Covid-19 pandemic is, it’s given us at least one benefit: we’ve utterly crushed the flu virus.

That’s right–the flu has almost completely disappeared this year. A combination of social distancing, closed schools and businesses, dramatically reduced travel, and high flu vaccination rates has achieved something that most flu experts never thought possible.

Flu levels are so low, in fact, that one has to wonder if the flu will even come back next year. The levels now are far lower than we’ve ever seen in modern history. Let’s take a look at the numbers:

nfluenza cases reported to the CDC by US public health laboratories, 2020-2021 season. Data from the CDC, graph created by the author.

As you can see here, the very worst week had just 24 confirmed cases in the entire U.S. That is truly astonishing. And in 2021 so far, we’ve had 5 or fewer cases in the entire country each week. Basically, the flu is gone. To see how dramatic this is, let’s look at data from last year (the winter of 2019-2020), which was a typical flu season:

Influenza cases reported to the CDC by US public health laboratories, 2019-2020, season. Data from the CDC, graph created by the author.

As you can see above, the U.S. had about 3,000 cases per week in January and February of 2020, with a peak at nearly 4,000 cases.

The rate of influenza this year is over 100 times lower than it’s ever been. Why did this happen? It’s obvious: all of the precautions we’re taking to reduce the spread of Covid-19 have worked wonders to prevent the flu as well. In fact, they’ve worked far better for influenza than for the Covid-19 virus.

No one knows what the flu season will look like next year, but for now, at least we’ve won a clear victory against the influenza virus. That’s a bit of good news.

RNA vaccines have arrived. Let's starting making them for influenza, right now.

The race to end the Covid-19 pandemic will be won by vaccines. We now have at least four approved vaccines, and the first two–the fastest to be developed and approved–were both RNA vaccines, a new technology that has never before been used on a large scale.

As I’ve written before, these RNA vaccines are a scientific triumph. Both the Moderna vaccine and the Pfizer/BioNTech vaccine are 95% effective against the virus. Both were developed in a matter of days–days!–after the genome sequence of the Covid-19 virus, SARS-CoV-2, was first revealed.

Now that we know that RNA vaccines work, what’s stopping us from designing and deploying this technology for many other infections that we don’t yet have under control? Simply put: nothing. We just need to have the will to do it, and it will happen. By which I mean, we need the government to pay for it.

Once Covid-19 fades, as it will, we’ll still have to deal with influenza, which sweeps through the population every year, often mutating significantly from the previous year. That’s why we need a new flu vaccine every year: the flu itself mutates to escape the protection we have from last year’s vaccine.

(Aside: we’re in the midst of the mildest flu season in decades, perhaps ever, thanks to the Covid-19 restrictions. The CDC reports fewer than 100 confirmed cases of influenza in the entire country, at a time when we’d usually be seeing thousands of cases per week.)

RNA vaccines are remarkably easy to design, and they’re much cheaper than conventional vaccines too. We should be thinking about making them for a raft of illnesses now: not just flu, but malaria, HIV, and others. But let’s start with the flu.

We already know that we need a new flu vaccine every year, so here’s a not-so-radical proposal: let’s create an RNA vaccine for the flu, right now, paid for by the government. It’s almost certain to work, and it will likely work far better than the current vaccine. Here’s why.

For the current flu vaccines, we create a new vaccine every year based on what’s currently circulating among humans. For the Northern hemisphere, we choose the vaccine strain right around now (late January or early February), because it takes 6 months to prepare the vaccine for the following fall.

The flu vaccine production uses a crude, decades-old process. After choosing a vaccine strain, the manufacturers (GlaxoSmithKline is one) isolate the virus and then inject it into chicken eggs, where they let it grow for 4-5 days. The virus is then extracted from the eggs, killed, and stuck into a syringe. That’s basically it. (This is why people who have egg allergies are sometimes warned not to get the flu vaccine.)

There are loads of problems with this process. First, it often turns out (and this is not widely known) that the first choice for a vaccine strain doesn’t grow well in eggs. In those years, the manufacturers move on to a second, third, or fourth choice, until they find one that grows in chicken eggs. These inferior choices, in turn, lead to vaccines that are less effective at conferring immunity.

Second, the process requires huge, messy chicken farms, which means it is slow and costly. Third, even though the virus is a killed virus, there’s always a small chance that some live virus will survive and infect people.

RNA vaccines, in contrast, can be manufactured precisely to match the virus that you wish to target. There’s no need to grow it in chicken eggs. And it’s far cheaper to make. In addition, you only need a fragment of a virus to make the vaccine, so there’s zero chance that anyone can ever be infected from the vaccine. And we know exactly what to target on the influenza virus: the hemagluttinin and neuraminadase proteins that cover the surface of the virus.

If RNA vaccines are so good, one could argue, why not allow the free market to produce them? Because it just won’t happen: the flu vaccine is not very profitable, and getting an entirely new vaccine approved is very expensive. Private companies just aren’t going to do it; on the contrary, several past flu vaccine manufacturers dropped out of the business because it just wasn’t profitable.

(Interesting story: about 15 years ago, I attended a talk by Anthony Fauci about influenza. At the time, I was leading a large-scale effort to sequence thousands of influenza viruses, a project that continues to this day and that is run by Dr. Fauci’s institute, NIAID. At the end of his talk, I asked Dr. Fauci why the NIH itself couldn’t sponsor flu vaccine development. He answered that it just wasn’t done that way–that NIH handled the basic research, but left vaccine development to industry. Well, Covid-19 has changed all that.)

We don’t have to create a new government-run facility to make the vaccines in order for this to work. Instead, we can do exactly what we did for Covid-19: pre-purchase a large supply of RNA-based flu vaccines, and provide generous funding to pay for the vaccine development and testing. Then companies like Moderna and Pfizer will have proper incentives to use their technology on influenza.

The health benefits of new, better vaccines are far too important to leave this to private companies, who are motivated more by profits than by an interest in public health. Let’s use the scientific success of RNA vaccines to change the way vaccine development works in a big way. We can save untold numbers of lives if we do.