A possible treatment for COVID-19?

Amidst all of the unproven and ineffective treatments being promoted for coronavirus treatment, a new possibility has just emerged.

Scientists around the globe are devoting enormous resources to trying to develop new treatments for COVID-19, the pandemic that is sweeping across the world. So far, though, we don't have any effective therapies or vaccines.

That might be about to change. What's particularly exciting is that this new treatment uses a widely-available drug that has already been shown to be safe in humans.

In a new preprint, a team of my colleagues at Johns Hopkins University School of Medicine, led by Maximilian Konig, Bert Vogelstein, Joshua Vogelstein, Susan Athey, Shibin Zhou, and Chetan Bettegowda, describe the potential of prazosin to slow down and possibly prevent one of the worst effects of COVID-19: the cytokine storm.

[Some background: a cytokine storm is an extreme immune response of your own body. When coronavirus (SARS-CoV-2) enters the lungs, your immune system responds with virus-fighting cells that release small proteins called cytokines. In some cases, the immune system just keeps amplifying its response, sending more and more cytokines even though the infection might be under control. If it gets too bad, the cytokine storm itself may be fatal. Cytokine storms have been implicated in other viral diseases, including influenza and SARS.]

Let me start with a caveat: if prazosin works, it isn't a cure. However, it might prevent the need to go on a ventilator, which would be a huge benefit in a country (and a world) that has a severe shortage of ventilators right now. Even more important, it might save patients with severe COVID-19 from dying.

Several of the scientists involved in this new study have shown previously that drugs like prazosin (which are known technically as alpha-1AR antagonists) can prevent a cytokine storm–in mice. They realized that results in mice often fail to translate to humans, but in the current pandemic, how could they find time to do a new study?

They didn't: instead, they looked at a medical database and collected records from 13,125 men who had acute respiratory distress (ARD) from a variety of causes in the years 2007-2015. ARD is not the same as COVID-19, but it's similar; and if a cytokine storm occurs in ARD, patients are more likely to require a ventilator and/or die. Because prazosin is widely used by men (most commonly for enlarged prostates), they were able to compare the outcomes of men who had incidentally been taking prazosin to men who hadn't.

The results: men who had been taking prazosin had a 22% lower risk of either needing a ventilator or dying. That's not a huge effect, but it could be a game changer for our overwhelmed hospitals in the midst of this pandemic. Even a modest reduction in the number of patients needing ventilators–or dying–would be a huge win for public health. Also, the patients in this retrospective study weren't taking prazosin to treat their respiratory distress, and it's possible that higher doses might have a larger effect.

There are many more caveats here. First, the study I'm describing is a medRxiv preprint, meaning that it has not been peer-reviewed. In addition, the data are from a retrospective study of men who had a different disease, not COVID-19. So maybe prazosin won't work to prevent cytokine storms caused by the coronavirus.

But maybe it will. My colleagues shared their preprint with me because they are convinced that, if nothing else, their hypothesis needs to be examined by as many scientists and doctors as possible. They are starting their own clinical trial, but they hope that these preliminary findings "will inspire immediate clinical trials in countries now desperate for new ways to reduce hospital admissions, ventilator needs, sickness, and death."

Prazosin has been in medical use since 1974 and is widely available and inexpensive. It's one of the most promising treatments I've heard of, far more promising than hydroxychloroquine. Even if it only slightly reduces the need for ventilators, it may have a huge impact on this pandemic. We need to start investigating it right away.

(Note: I've made it a rule not to write columns about my own or my colleagues' scientific accomplishments. Many rules are being broken in this pandemic, and I decided the urgency of this potential treatment was more than sufficient to break my usual rule.)

A new kind of fasting provides significant immune system benefits

I've written about fasting and its effects on health before. Six years ago, a study showed that a 3-day fast can essentially reset the immune system, providing many potential benefits. These benefits include better cardiovascular health, better endurance, lower blood pressure, and reduced inflammation.

Newer data, which I'll get to in a minute, shows that you might not have to fast nearly that long to get these benefits.

In the 2014 study, Valter Longo and colleagues at USC found that fasting lowered white blood cell counts, which in turn triggered the immune system to start producing new white blood cells. White blood cells (or lymphocytes) are a key component of your body’s immune system. Once you start eating again, according to Longo, your stem cells kick back into high gear to replenish the cells that were recycled.

The idea behind this strategy is that you have to fast for several days to get the benefits: basically, you have to fully deplete your energy reserves (in the form of glycogen), and it takes your body at least 24 hours, and probably 48 hours or more, to do this. That's the not-so-good news. The good news is that you probably only need to fast once or twice a year to gain the benefits that Longo described.

Last week, in a paper just published in the New England Journal of Medicine, Rafael de Cabo and Mark Mattson reviewed multiple strategies for fasting that have been tested in the years since Longo's study. The news continues to be very encouraging: intermittent fasting is good for you. I don't have time or space here to discuss all the results, but I want to focus on one fasting strategy that has surprisingly good benefits.

It turns out that you can get many of the benefits of fasting without doing a 3-day fast, which for most people is really, really difficult to accomplish. Instead, you can try a much easier type of fasting, called "time-restricted" fasting. With this strategy, you fast every day, by eating all of your food in a 6-hour or 8-hour window. Or you can go with the more difficult strategy (but still easier than a 3-day fast) where you fast for 2 entire days per week. Here, then, are two intermittent fasting strategies that have similar health benefits:

• Time-restricted: eat lunch starting at 12 noon, and finish dinner by 8:00pm. Fast until the next day at noon (16 hour fast). Do this every day.
• 5:2 fasting: fast for 2 different days each week, which means eating just 500-700 calories worth of food and drink on those days. Eat normally on the other 5 days.

The first strategy–a daily 16-hour fast–is the easiest, but its benefits might be equal to those of 5:2 fasting and the 3-day fast. (No study has directly compared these 3 fasting regimens.)

The benefits of intermittent fasting are numerous. As de Cabo and Mattson explain, they include

"[improvements in] blood pressure; resting heart rate; levels of HDL and LDL cholesterol, triglycerides, glucose, and insulin resistance.... In addition, intermittent fasting reduces markers of systemic inflammation and oxidative stress that are associated with atherosclerosis."

Fasting also helps with weight loss, for obvious reasons. Cutting out all snacks in the evening, which is the biggest change imposed by time-restricted fasting, means not only a reduction in calories consumed, but also a reduction in the amount of highly processed ("junk") foods in one's diet as well.

Furthermore, because intermittent fasting reduces inflammation, it may also improve symptoms of arthritis and even rheumatoid arthritis.

Why does fasting work? It's all about getting your body to switch over from glucose metabolism to ketone metabolism. Our usual 3-meal-a-day diet provides our body with a constant source of fuel in the form of glucose. Once that glucose is used up, though, our body switches to using fatty acids and ketone bodies. Ketone bodies provide more than fuel: as de Cabo and Mattson explain,

"Ketone bodies regulate the expression and activity of many proteins and molecules that are known to influence health and aging."

Ketone metabolism seems to bring a host of health benefits. The trick is getting our bodies to switch over to it, now and then. If we eat constantly, then our bodies happily subsist on glucose and never make the switch.

Does fasting truly reset your immune system? Six years ago, I concluded that a 3-day fast does the trick, at least partially. The science suggests that, if you can do it, a prolonged fast for 2-3 days will induce your body to clean out some old immune cells and switch on production of new ones. Now we're learning that intermittent fasting, which is easier to do, may work in much the same way, with multiple health benefits.

[Note: one of the authors of the NEJM study, Mark Mattson, is a Professor at Johns Hopkins School of Medicine, making him a colleague of mine. However, we are in different departments and we have never met.]

The top 6 vitamins and supplements you shouldn’t take

The evidence against supplements continues to pile up.

Recently I created a list of The Top 5 Vitamins You Shouldn’t Take. Now I’m expanding that list to include vitamin D, which is taken by almost half of older adults. Now, two new studies in latest issue of The Lancet show that most of these people are wasting their money.

The first study is a large review by Philippe Autier and colleagues, who found that taking supplemental vitamin D has no effect on a wide range of diseases and conditions. After looking at over 450 studies, the authors conclude:

“The absence of an effect of vitamin D supplementation on disease occurrence, severity, and clinical course leads to the hypothesis that variations [in vitamin D levels] would essentially be a result, and not a cause, of ill health.”

So it appears that we’ve been getting cause and effect backwards, at least as far as vitamin D is concerned. Autier looked at non-skeletal disorders, including heart disease, weight gain, mood disorders, multiple sclerosis, and metabolic disorders, all of which have been linked to lower vitamin D. In trial after trial, supplemental vitamin D had no beneficial effect on any of these conditions. Autier et al concluded that:

“associations between 25(OH)D and health disorders … are not causal. Low 25(OH)D [vitamin D] could be the result of inflammatory processes involved in disease.”

Instead, the researchers found, in study after study, that low vitamin D was the result of poor health, not the cause.

The Autier study didn’t look at the biggest supposed benefit of vitamin D: protection against osteoporosis. We’ve long known that vitamin D is associated with bone health. Fortunately, in the same issue of The Lancet, Ian Reid and colleagues looked closely at this question. They reviewed 23 studies with 4082 participants, all designed to determine at whether supplemental vitamin D improves bone density. Their findings? It doesn’t help. They concluded:

“Continuing widespread use of vitamin D for osteoporosis prevention in community-dwelling adults without specific risk factors for vitamin D deficiency seems to be inappropriate.”

Vitamin D supplements, to put it plainly, are a waste of money.

(For those concerned about osteoporosis, the widely used drug alendronate (Fosamax®), has been shown to increase bone density by about 5%, as explained in a 2011 article by Dr. Sundeep Khosia. But Fosamax has side effects.)

It’s pretty easy to get enough vitamin D in a normal diet. Or, as Dr. Mark Gillinov explained in the Huffington Post last week, just 10 minutes of sunlight gives you about 4 times your daily recommended vitamin D requirement.

So here's my expanded list of the Top Six Vitamins You Shouldn’t Take, with the newest entrant at the end:

1. Vitamin C
2. Vitamin A and beta carotene
3. Vitamin E
4. Vitamin B6
5. Multi-vitamins
6. Vitamin D

You can read more about the first five in the original list.

What’s left? Well, if you don’t have a deficiency, there’s no reason to take any supplemental vitamins at all.  As my Hopkins colleagues Eliseo Guallar, Lawrence Appel, and Edgar Miller wrote last month in the Annals of Internal Medicine : “Enough is enough: stop wasting money on vitamin and mineral supplements.”  As they wrote, after looking at three more large studies just published last month,

"most supplements do not prevent chronic disease or death, their use is not justified, and they should be avoided."

Save your money. Or better yet, if you must spend it, buy a bit more fresh fruit. You'll be healthier for it.