Saturated fat and low-carb diets: Still more to learn?

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Various versions of low-carbohydrate diets have been popular for many years. The details of what is allowed and what is not vary quite a bit, and the amount of carbohydrates also differs. Too often these diets contain plates piled high with bacon, meat, eggs, and cheese. Due to the high saturated fat content in these diets, doctors and nutritionists worry about their potential adverse effect on cardiovascular disease.

The American Heart Association recommends aiming for about 13 grams of saturated fat, which is about 6% of 2,000 calorie diet. Recently, a new study published in the American Journal of Clinical Nutrition suggests that at least in the short term a low carb diet with a higher amount of saturated fat might still be heart-healthy. But is it that simple? Let’s take a look at what this randomized diet trial did and what the results really mean.

What did the study actually involve?

The 164 participants in this study were all considered overweight or obese, and had just finished a weight loss trial to lose 12% of their body weight. They were randomly assigned to one of three diets containing different proportions of carbohydrates and fat. Protein content was kept the same (at 20% calories) for everyone. They were not planning to lose any more weight.

The three diets were:

  • Low carbohydrates (20%), high fat (60%), saturated fat comprising 21% of calories: this resembles a typical low-carbohydrate diet and has much higher saturated fat than recommended.
  • Moderate carbohydrate (40%), moderate fat (40%), saturated fat comprising 14% of calories: this is not far from the typical American diet of 50% carbohydrates and 33% fat, and it is quite similar to a typical Mediterranean diet, which is slightly lower in carbohydrates and higher in fat than an American diet.
  • High carbohydrate (60%), low fat (20%), saturated fat comprising 7% of calories: this meets the recommendation of the Dietary Guidelines for Americans and is a typical high-carbohydrate diet, including a lot of grains, starchy vegetables, and fruits or juices.

The study participants received food prepared for them for 20 weeks. They had their blood measured for a number of risk factors of cardiovascular disease, and a lipoprotein insulin resistance (LPIR) score was calculated using a number of blood markers to reflect the risk for cardiovascular disease. (LPIR is a score that measures both insulin resistance and abnormal blood cholesterol all in one number, and it is used for research purposes.)

The researchers found that at the end of eating these diets for five months, the participants in each of the three groups had similar values of cardiovascular disease markers, such as the LIPR score an and cholesterol blood levels.

What were the participants actually eating?

Alas, those who were eating the low-carbohydrate diet were not piling up their plate with steak and bacon, and those eating the high-carbohydrate diets were not drinking unlimited soda. All three diets were high in plant foods and low in highly processed foods (it is easier to stick to a diet when all the food is prepared for you). Even the low-carbohydrate group was eating lentils, a good amount of vegetables, and quite a bit of nuts.

Even the two diets with higher than recommended amounts of saturated fats also were high in the healthy poly- and monounsaturated fats as well. For example, the diets contained a combination of higher amounts of healthy (salmon) and a small amount of unhealthy (sausage) choices. In addition, fiber intake (at about 22 grams/day) was slightly higher than the average American intake (18 grams/day). Overall, except for saturated fat being higher than recommended, the diet as a whole was quite healthy.

What is the take-home message?

Striving for a plant-based diet with saturated fat being limited to 7% of total calories remains an ideal goal. But for people who choose a low carb, high fat diet to jump start weight loss, keeping saturated fat this low even for a few months is challenging. This study at least provides some evidence that higher amounts of saturated fat in the context of a healthy diet do not seem to adversely affect certain cardiovascular risk markers in the short term. How it would affect actual disease — such as heart attack, stroke, and diabetes — in the long run is unknown. However, there is ample evidence showing that a diet that consists of healthy foods and has moderate amounts of carbohydrate and fat can lower the risk of these diseases.

Preventing diseases is a long-term process; a healthy diet must not only be effective, but it should also be flexible enough for people to stick to in the long run. Could a diet with lower amounts of healthy carbohydrates and ample healthy fats with a bit more saturated fat be healthy enough? As the researchers state, we need long-term testing to help answer the question.

Minimizing successes and magnifying failures? Change your distorted thinking

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Some things are not debatable. Rain falls from the sky. Elevators go up and down. Orange traffic cones are orange. But because we interpret the world through our experiences, a lot isn’t so definitive.

The boss might say, "Good job," and we wonder why they didn’t say, "Great job." We see someone looking in our direction and they seem angry, so we believe that they’re mad at us, and no other explanation makes sense.

What’s happening is that we’re distorting our experience, jumping to conclusions, mind reading, and going to the worst-case scenario. When we do this, we shrink our successes and maximize our "failures," and because it can be an automatic process, it’s hard to tell when it’s happening. "You don’t know you’re wearing magnifying glasses," says Dr. Luana Marques, associate professor of psychology at Harvard Medical School.

So what can you do to see things more clearly and with a more balanced perspective? It takes practice and a willingness to tolerate discomfort, but as with addressing any problem, it starts with awareness.

What’s happening when we magnify failures and jump to negative conclusions?

We like to process information quickly, and we use filters to help do that. If we believe, "I’m no good," all words and behaviors that support that contention just make everything easier.

"The brain doesn’t want to spend energy trying to fight that," Marques says. And the brain responds depending on the distortion. If something causes anxiety, say from a curious look or comment, the limbic system is activated and we’re in fight-or-flight mode, hyper-focused on the threat, not thinking creatively or considering alternative, less threatening options.

But sometimes, there’s no threat in play. We’re just thinking, probably overthinking, when we question our abilities and minimize our accomplishments.

So what can you do about it?

Label the type of thinking distortion

It helps to define our distortions, the common ones being:

  • Catastrophizing: Taking a small incident and going to the worst-case scenario.
  • Black-and-white thinking: Seeing only all-or-nothing possibilities.
  • Jumping to conclusions: Assuming what will happen rather than waiting to see what will actually happen.
  • Mind reading: Assuming what someone is thinking without much evidence.

When you label it, you can better understand and recognize what your go-to distortion is, because "we tend to do one more than another," Marques says.

After that, it helps to take your emotional temperature by asking: Am I stressed? Am I sweating? Is my heart pounding or my breathing shallow? It brings you more into the moment and it allows you to think about what you were doing that brought on the response, such as, "I was trying to guess the outcome." It’s another way to pinpoint the distortion you tend to favor, she says.

Challenge the distortion

Whichever distortion it is, you want to examine your assumption by looking for other evidence. If you question your boss’s reaction to you, ask yourself: What does my boss really say? What does this person say about other people? Have I received raises and promotions? Am I given good projects?

An easy trap with distortions is that they’re plausible. A person who is mad at me would give me a look. A person who hated me wouldn’t text me back. Maybe so, but think of five other possible explanations, Marques says. This exercise engages the prefrontal cortex, which takes you out of the fight-or-flight mode and expands your thinking. You’re then problem-solving and not solely keyed on one option.

You also want to ask an essential question: is this thinking helpful? You might realize that all your thinking/wondering/worrying does is make you anxious. Gaining that presence might be enough to get you off the path of distorted thinking. "Asking and answering the question about your thinking pauses the brain, and you potentially see the world differently," she says.

Being balanced and kind to ourselves

As you examine and attempt to control your distortions, be mindful of how you treat yourself. Self-criticism is a really easy trap to fall into, but try talking to yourself as you would a friend. Better yet, imagine you’re speaking to a child. Your language would be considerate, supportive, and you wouldn’t use words such as "stupid" or "dumb." This approach also shifts you into the detached, third person. "You get out of your head," Marques says. "We’re cleaning our magnifying glasses a little bit."

Lastly, realize that you’re not looking to switch your attitude from "I’m unworthy" to "I’m super-great." That’s just trading one extreme for another. All you want is to counterbalance your distortion, then let it go. Countering thinking distortions is a lot like meditation, where you practice acknowledging your thoughts without getting hooked onto them.  "You don’t have to magnify or minimize." Marques says.

Navigating a chronic illness during the holidays

As a doctor, I am constantly advising my patients to prioritize their own mental and physical health. Get adequate sleep. Eat healthy. Learn how to say no so you don’t collapse from exhaustion. Love and care for yourself like you do others.

I talk the talk but don’t always walk the walk — even though I know, both intellectually and physically, that self-care is critical to my well-being. When I am run down, my MS symptoms cry out for attention: left leg weakness and numbness, subtle vertigo, a distinct buzzing in my brain like a relentless mosquito that won’t go away no matter how many times I twitch and shake my head. I have become frighteningly good at ignoring these symptoms, boxing them up and pushing them away. Often, I can muscle through; other times it just hurts.

Recently, a friend challenged me to think about my relationship with my illness, to describe MS as a character in my story. This was a useful exercise. I conjured up an image of a stern teacher. She is frighteningly blunt and lets me know, loud and clear, when I disappoint her. She can be mean and scary, and I don’t really like her. But I must admit she is usually right. Still, I often defiantly dismiss her, even when part of me knows this is not in my best interest.

This holiday season, I wanted to do better. I needed to do better. So, as Thanksgiving approached, as I prepared to host 16 family members, many for multiple days, I paused to ask myself, What does MS have to teach me about self-care? I don’t like having this disease, but I do. I can’t change my reality, so I might as well benefit from the lessons MS is forcing on me. I believe they are relevant to all of us, whether we live with chronic illness or not, so I’ll share them here.

The first steps: Listen and observe

When my MS symptoms flare, it’s a message that I am tired, overextended, and stressed. I need to rest. I don’t always listen right away, but eventually I am forced to, and when I listen, I feel better. All of us can benefit from slowing down and tuning in to our physical selves. What sensations are you experiencing in your body, and what does this tell you about your underlying feelings and state of mind? Yes, we should heed our thoughts, but tuning in to our bodies takes us deeper, to feelings that might be hidden, secrets we might not want to acknowledge, a physical truth. If you don’t have a chronic illness, the messages might be more subtle — a vague tightness in your chest, a quick catch in your breath, a barely noticeable tremor in your hands — but they exist, and they signal stress.

The science is clear: the body’s stress response — though potentially lifesaving in a true emergency, when “fight or flight” is essential to survival — can be toxic in our everyday lives. Stress triggers our sympathetic nervous system to kick into overdrive in response to a perceived threat, releasing hormones such as cortisol and inflammatory molecules that, when produced in excess, fuel disease. Conversely, we know that pausing to take notice and interrupting this negative cycle of stress is beneficial. It can be as simple as breathing deeply and counting to 10. Our bodies know what’s up and let us know when we need to take care of ourselves. We must pay attention.

You are not responsible for everyone and everything

The holidays, essentially from mid-November through the end of the year, are a stress test we create for ourselves. The land mines are everywhere: more food, more drinking, more family dynamics, more unfamiliar (or overly familiar) surroundings. Personally, with my overinflated sense of responsibility, I experience a kind of dizzying performance anxiety every holiday season. I believe it is my job to make sure everyone present has a positive experience. For better or worse, I am someone who notices and feels the personal and interpersonal dynamics in a room. I sense and absorb even the most subtle discomfort, frustration, anger, shame, and insecurity, alongside the more upbeat emotions. Importantly, I also I feel the need to step in and make things better, to prop everyone up. It’s exhausting. But MS reminds me of how absurd, and even egotistical, this is. In truth, I can’t possibly care for everyone. Neither can you.

It helps to check our automatic thoughts. More than once on Thanksgiving Day, as the busy kitchen buzzed with activity and conversation, I intentionally stepped back and watched, reminding myself that I didn’t have to hold the whole thing up. Even though I inevitably slipped back into hyper-responsibility mode, these moments of self-awareness impacted my behavior and the dynamic in the room.

It’s okay to say what you need

To take full responsibility for my own well-being, I need to speak honestly and act with integrity. This means asking for what I need, clearly and without apology. Historically, I have been terrible at this in my personal life, burying my own needs in the name of taking care of everyone else’s, even rejecting clear offers of help. “I’m good, I’ve got it,” I might say, while simultaneously feeling bitter and resentful for having to do it all myself. This lack of clarity isn’t fair to anyone. MS reminds me that I need to do better.

This year, when my guests asked me what they could bring, I took them at their word and made specific requests instead of assuring everyone that I had it covered. When my mother started banging around in the kitchen at 7 a.m. with her endearing but chaotic energy, asking for this and that pot and kitchen utensil so she could start cooking, I told her I needed to sit down and have a cup of coffee first. She would need to wait or find things herself. She was okay with that. Family dynamics can be entrenched and hard to change, but clear communication can set new ways of being into motion, one baby step at a time.

I still have a lot to learn, but I am making stuttering progress, learning to listen to my body and honor my needs while also caring for those I love, or at least trying. Undeniably, I experienced some post-Thanksgiving fatigue, exacerbated by my daughter’s early-morning hockey game the next day, requiring a 4:30 a.m. departure. I felt it in my body — the familiar leg weakness, vertigo, and brain cobwebs — and, completely uncharacteristically, I took a nap.

5 numbers linked to ideal heart health

How well are you protecting yourself against heart disease, the nation’s leading cause of death? A check of five important numbers can give you a good idea.

“For my patients, I typically look at their blood pressure, blood sugar, LDL cholesterol and triglycerides values, and their waist circumference,” says Harvard Heart Letter editor-in-chief Dr. Deepak L. Bhatt, who directs interventional cardiovascular programs at Harvard-affiliated Brigham and Women’s Hospital. Those values provide a picture of a person’s overall health and, more specifically, what factors they may need to address to lower their chance of a heart attack or stroke, he says.

Below are the ideal values for each measurement, along with why they’re important and targeted advice for improving them. Universal suggestions for improving all five measurements appear at the very end.

How do your heart health numbers stack up?

While the ideal values are good goals for most people, your doctor may recommend different targets based on your age or other health conditions.

Blood pressure

Less than 120/80 mm Hg

Blood pressure readings tell you the force of blood pushing against your arteries when your heart contracts (systolic blood pressure, the first number) and relaxes (diastolic blood pressure, the second number). Your blood pressure reflects how hard your heart is working (when you’re resting or exercising, for example) and the condition of your blood vessels. Narrowed, inflexible arteries cause blood pressure to rise.

Why it matters to heart health: High blood pressure accelerates damage to blood vessels, encouraging a buildup of fatty plaque (atherosclerosis). This sets the stage for a heart attack. High blood pressure forces the heart’s main pumping chamber to enlarge, which can lead to heart failure. Finally, high blood pressure raises the risk of strokes due to a blocked or burst blood vessel in the brain.

What helps: A diet rich in potassium (found in many vegetables, fruits, and beans) and low in sodium (found in excess in many processed and restaurant foods); minimizing alcohol.

LDL cholesterol

Less than 100 mg/dL

A cholesterol test (or lipid profile) shows many numbers. Doctors are usually most concerned about low-density lipoprotein (LDL) cholesterol, particles that makes up about two-thirds of the cholesterol in the blood.

Why it matters to heart health: Excess LDL particles lodge inside artery walls. Once there, they are engulfed by white blood cells, forming fat-laden foam cells that make up atherosclerosis.

What helps: Limiting saturated fat (found in meat, dairy, and eggs) and replacing those lost calories with unsaturated fat (found in nuts, seeds, and vegetable oils).

Triglycerides

Less than 150 mg/dL

Perhaps less well-known than cholesterol, triglycerides are the most common form of fat in the bloodstream. Derived from food, these molecules provide energy for your body. But excess calories, alcohol, and sugar the body can’t use are turned into triglycerides and stored in fat cells.

Why it matters to heart health: Like high LDL cholesterol, elevated triglyceride values have been linked to a higher risk of heart attack and stroke.

What helps: Limiting foods that are high in unhealthy fats, sugar, or both; eating foods rich in omega-3 fatty acids (such as fish); avoiding alcohol.

Blood sugar

Less than 100 mg/dL

High blood sugar defines the diagnosis of diabetes. Type 2 diabetes is most common. It occurs when the body develops insulin resistance (insulin enables cells to take in sugar) and does not produce enough insulin to overcome the resistance.

Why it matters to heart health: High blood sugar levels damage blood vessel walls and cause sugar (glucose) to attach to LDL. This makes LDL more likely to oxidize — another factor that promotes atherosclerosis. Excess sugar in the blood also makes cell fragments called platelets stickier so they’re more likely to form clots, which can trigger a heart attack or stroke.

What helps: Avoiding sugary beverages and foods high in sugar; eating whole, unprocessed grains instead of foods made with refined grains (white flour, white rice).

Waist circumference

Whichever number is lower:

Less than half your height in inches

OR

Women: Less than 35 inches

Men: Less than 40 inches

Measure your waist around your bare abdomen just above your navel (belly button). A big belly — what doctors call abdominal or visceral obesity — usually means fat surrounding internal organs.

Why it matters to heart health: Visceral fat secretes hormones and other factors that encourage inflammation, which triggers the release of white blood cells involved in atherosclerosis.

What helps: Consuming fewer calories, especially those from highly processed foods full of sugar, salt, and unhealthy types of fat.

Universal advice to improve all five measures of heart health

If one or more of your numbers is above ideal levels, you’re far from alone. Most Americans are overweight or obese and have bigger-than-healthy bellies. Excess weight and waist circumference affect blood pressure, LDL cholesterol, triglycerides, and blood sugar. Eating a healthy, plant-based diet can help. Regular exercise also helps: aim for at least 30 minutes of moderate-intensity exercise like brisk walking most days. Other lifestyle habits that can lower your heart disease risk include getting seven to eight hours of sleep nightly and managing your stress level.

Skin in the game: Two common skin problems and solutions for men

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When I was on the junior varsity basketball team in high school, I wasn't surprised when I developed a case of itchy, flaky athlete's foot. After all, I was an "athlete," so I assumed it was a sign of dedication and hard work.

I was shocked when my mother told me the truth: it was due to poor foot hygiene, not my dribbling skills.

Fast-forward almost four decades, and I’m much more diligent about skin care. Still, some skin issues plague me at times, like they do many men. Here is a look at two common problems and solutions.

Dry skin

Symptoms of dry skin include scaly patches (with or without redness), itching, and overall dryness. You can get dry skin year-round — from the heavy heat of summer to the bitter cold of winter. Sun exposure damages skin, leaving it thinner and less likely to hold in moisture over time. Also, aging skin produces less of the natural oils that keep skin lubricated.

Treatment. The first line of defense is a moisturizer that softens and smooths skin with water and lipids (fats). Some moisturizers attract water to the skin and seal it in. Others prevent moisture loss by coating skin with a thick, impermeable layer.

  • Petroleum jelly. This waxy, greasy substance stops water loss without clogging pores. It can be used by itself but is also an ingredient in many moisturizers and ointments. Because petroleum jelly doesn’t contain water, it’s best used while the skin is still damp after bathing to seal in moisture.
  • Mineral oil. Mineral oil has the same effect but without a greasy feeling. It also should be used while skin is damp.
  • Moisturizing lotions and creams. These products contain both water and oils. They’re less greasy and more cosmetically appealing than petroleum jelly or oils. Look for moisturizers with at least one of the following ingredients: glycerin, urea, pyroglutamic acid, sorbitol, lactic acid, lactate salts, or alpha hydroxy acids.

Prevention. Try a few changes to help prevent dry skin:

  • Add moisture to the air with a humidifier or a pan of water set atop the radiator.
  • In the shower or bath, use lukewarm water (hot water can dry the skin by stripping it of natural oils).
  • Choose nondrying soaps with no abrasives or irritants. Super-fatted soaps or cleansing bars are less drying than regular, liquid, or antibacterial soaps.
  • To retain the water your skin absorbs while showering or bathing, apply jelly, oil, or moisturizer immediately afterward.

Athlete’s foot

Athlete’s foot is caused by dermatophytes, a group of fungi on the surface of the skin. Tell-tale signs include intense itching; cracked, blistered, or peeling areas of skin, especially between the toes; and redness and scaling on the soles. Dermatophytes thrive in warm, moist environments like pools, showers, and locker rooms where people walk with bare feet. The warm, moist environment of sweaty socks and shoes encourages them to grow.

Treatment. First, try an over-the-counter antifungal ointment, cream, or powder, such as clotrimazole (Lotrimin AF, Mycelex, generic), terbinafine (Lamisil AT, Silka,), or miconazole (Lotrimin AF spray, Micatin). It can take weeks for an infection to improve, and recurrences are common. If symptoms don't improve after several weeks, consult a doctor, who may prescribe antifungal pills.

Prevention. Keeping feet clean and dry is the best way to ward off athlete’s foot. Also, do the following:

  • Wash your feet well every day, and wear a clean pair of socks after your bath or shower.
  • Take time to dry your feet thoroughly (including each toe and especially the web space between the toes) after you bathe, shower, or swim.
  • Wear flip-flops or sandals around public pools and in gym locker rooms and showers.
  • Wear moisture-wicking socks that absorb sweat.
  • Don’t wear the same shoes two days in a row. Give shoes a 24-hour break between wearings to air out and dry.

What it takes to achieve world-changing scientific breakthroughs

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In science, advances are a daily occurrence, but true breakthroughs are rare. What does it take to achieve world-changing scientific breakthroughs? Some are the result of a lucky accident, combined with curiosity: scientists traveling down one road suddenly find reason to veer onto another road, one they never planned to travel — a road that may well lead nowhere.

Other major breakthroughs stem from scientists pursuing a very specific dream. One day, usually early in their career, they get an idea that they can’t stop thinking about. It’s crazy, they say to themselves, but is it really impossible? They talk to respected colleagues who often remind them of all the reasons their idea might not work, and how damaging this could be for their career. It’s a sobering message, yet the idea won’t die. So, they scramble to find financial support and seek out colleagues willing to risk traveling that road with them — a road that may well lead nowhere. But sometimes the road leads to major breakthroughs like penicillin and mRNA vaccines.

Breakthroughs due to lucky accidents and curiosity

One day in 1928, Dr. Alexander Fleming at St. Mary’s Hospital in London was growing bacteria in a laboratory dish. Fleming was not pursuing a scientific dream. He was a microbiologist, just doing his job.

Then he noticed something odd: overnight, another kind of microbe, a fungus, had traveled through the air, landed on the laboratory dish, and started to grow and spread on the dish where the bacteria were growing. Fleming soon noticed that the growing fungus seemed to be killing the bacteria. He surmised that it was making some substance that killed the bacteria. Because the name of the fungus was Penicillium rubens, he called the substance the fungus was making “penicillin.”

When Fleming published a paper about his discovery, few were interested. It took another 10 years before other scientists tried to generate large amounts of penicillin to see if it might be able to cure bacterial infections and save lives. We all know how that worked out.

Fleming’s scientific breakthrough, like some others, occurred not because Fleming had a brilliant idea and exclaimed “Eureka!” Instead, it occurred because he noticed something and said, “That’s odd,” and then tried to figure it out.

Breakthroughs due to persistence and resilience in pursuit of a dream

The story of mRNA vaccines, like the Pfizer/BioNTech and Moderna vaccines for COVID-19, is very different from the story of penicillin. For 30 years, a small group of scientists believed that mRNA vaccines would have great advantages over traditional vaccines — if only several obstacles could be overcome. Many of these scientists gave up as they encountered those obstacles, but a few persisted and, ultimately, succeeded. (I described what mRNA vaccines are, how they work, and how obstacles were overcome in a previous blog post.)

One scientist, Dr. Katalin Karikó, joined the faculty of the University of Pennsylvania in the early 1990s with the dream of creating an mRNA vaccine. She applied for grants to support her work, but was repeatedly rejected: the reviewers stated that it was so unlikely that she or anyone could overcome the obstacles that supporting her research would be a wasted investment. Her university only agreed to continue supporting her work if she accepted a demotion and a pay cut. She accepted both, and doggedly pursued her dream.

One major obstacle to mRNA vaccines particularly fascinated her: the violent reaction of the immune system when it encounters mRNA from a virus. Ten years of dogged work helped Karikó and her colleague Drew Weissman figure out how to make a small change in mRNA that prevented that violent immune response — a major step in making all mRNA vaccines possible. Without this, the world wouldn’t have mRNA COVID vaccines today.

Two other scientists who created the Pfizer/BioNTech COVID vaccine, Uğur Şahin and Őzlem Turëci, are Turkish immigrants to Germany who met, fell in love with the idea of creating an mRNA vaccine, and then fell in love with each other. According to The Wall Street Journal, one day in 2002 they took a break for lunch, got married, and then returned in the afternoon to their laboratory to finish an experiment — just one more among many conducted over 30 years. Each experiment was one more possible step toward their ultimate dream until finally, in 2020, they achieved that dream: their mRNA vaccine for COVID-19 proved to be very safe and effective.

Holding hard to their dreams

Whichever path scientists who achieve lifesaving breakthroughs travel, they often endure disinterest, like Fleming, or repeated skepticism, ridicule, and rejection, like Karikó, Weissman, Şahin, and Turëci. Only through sheer persistence did these scientists bring their dreams to life. They have been rewarded with fame and wealth and something even more valuable: the knowledge that because of their work hundreds of millions of people around the world never got sick, and millions never died before their time.

Of course, a relentless obsession with an improbable dream fails to pay off for many scientists. Their ideas, while quite brilliant, in the end are proved wrong: nature doesn’t turn out to operate the way they predicted. In the end, their beautiful theory is murdered by a brutal gang of facts.

Still other scientific dreamers ultimately prove to have been on the right track all along and would have achieved their dream — if only they had done the experiment a little differently, if only they had persisted a little longer, or if only the support for their work had not run out. As a result, neither they nor the rest of us benefitted from what would have been — until other scientists rediscovered their work years later.

Ultimately, scientific breakthroughs are possible only if a society is willing to invest in dreamers, recognizing that not all investments will lead to major breakthroughs. However, the investments that do lead to breakthroughs bring an economic return that is far greater than the investment — as well as preventing suffering and death and changing the world.

Want to participate in COVID-19 research? Download the COVID Symptom Study app to help researchers track symptoms and hot spots across the US. Click here for information.

A new targeted treatment for early-stage breast cancer?

In the US, breast cancer is the most commonly diagnosed cancer in women, and the second leading cause of cancer-related deaths. Each year, an estimated 270,000 women — and a far smaller number of men — are diagnosed with it. When caught in early stages, it’s usually highly treatable.

A promising new form of targeted treatment may expand options available to some women with early-stage breast cancer linked to specific genetic glitches. (Early-stage cancers have not spread to distant organs or tissues in the body.)

The BRCA gene: What does it do?

You may have heard the term BRCA (BReast CAncer) genes, which refers to BRCA1 and BRCA2genes. Normally, BRCA genes help repair damage to our DNA (genetic code) that occurs regularly in cells throughout the human body.

Inherited BRCA mutations are abnormal changes in these genes that are passed on from a parent to a child. When a person has a BRCA mutation, their body cannot repair routine DNA damage to cells as easily. This accumulating damage to cells may help pave a path leading to cancer. Having a BRCA1 or BRCA2 mutation — or both — puts a person at higher risk for cancer of the breast, ovaries, prostate, or pancreas; or for melanoma. A person’s risk for breast cancer can also be affected by other gene mutations and other factors.

Overall, just 3% to 5% of all women with breast cancer have mutations in BRCAgenes. However, BRCA mutations occur more often in certain groups of people, such as those with triple negative breast cancer (TNBC), Ashkenazi Jewish ancestry, a strong family history of breast and/or ovarian cancer, and younger women with breast cancer.

Inherited BRCA mutations and breast cancer types

Certain types of breast cancer are commonly found in women with BRCA gene mutations.

  • Estrogen receptor-positive, HER2-negative cancer: Women with a BRCA2 mutation usually develop ER+/HER2- breast cancer — that is, cancer cells that are fueled by the hormone estrogen but not by a protein known as HER2 (human epidermal growth factor 2).
  • Triple negative breast cancer: Women with a BRCA1 mutation tend to develop triple negative breast cancer (ER-/PR-/HER2-) — that is, cancer cells that aren’t fueled by the hormones estrogen and progesterone, or by HER2.

Knowing what encourages different types of breast cancer to grow helps scientists develop new treatments, and helps doctors choose available treatments to slow or stop tumor growth. Often this involves a combination of treatments.

A new medicine aimed at early-stage BRCA-related breast cancers

The OlympiA trial enrolled women with early-stage breast cancer and inherited BRCA1/BRCA2 mutations. All were at high risk for breast cancer recurrence despite standard treatments.

Study participants had received standard therapies for breast cancer:

  • surgery (a mastectomy or lumpectomy)
  • chemotherapy (given either before or after surgery)
  • possibly radiation
  • possibly hormone-blocking treatment known as endocrine therapy.

They were randomly assigned to take pills twice a day containing olaparib or a placebo (sugar pills) for one year.

Olaparib belongs to a class of medicines called PARP inhibitors. PARP (poly adenosine diphosphate-ribose polymerase) is an enzyme that normally helps repair DNA damage. Blocking this enzyme in BRCA-mutated cancer cells causes the cells to die from increased DNA damage.

Results from this study were published in the New England Journal of Medicine. Women who received olaparib were less likely to have breast cancer recur or metastasize (spread to distant organs or tissues) than women taking placebo. Follow-up at an average of two and a half years showed that slightly more than 85% of women who had received olaparib were alive and did not have a cancer recurrence, or a new second cancer, compared with 77% of women treated with placebo.

Further, the researchers estimated that at three years:

  • The likelihood that cancer would not spread to distant organs or tissues was nearly 88% with olaparib, compared to 80% with placebo.
  • The likelihood of survival was 92% for the olaparib-treated group and 88% for the placebo group.

The side effects of olaparib include low white cell count, low red cell count, and tiredness. The chances of developing these were low.

The bottom line

Olaparib is already approved by the FDA to treat BRCA-related cancers of the ovaries, pancreas, or prostate, and metastatic breast cancer. FDA approval for early-stage breast cancer that is BRCA-related is expected soon based on this study. These findings suggest taking olaparib for a year after completing standard treatment could be a good option for women who have early-stage breast cancer and an inherited BRCA gene mutation who are at high risk for cancer recurrence and, possibly, its spread.

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Harvard Health Ad Watch: An upbeat ad for a psoriasis treatment

Psoriasis is a chronic disease in which skin cells rapidly divide, causing the skin to develop rough, red, scaly patches. Plaque psoriasis is the most common form: affected skin has sharply defined, inflamed patches (plaques) with silvery or white scales, often near an elbow or on the shins and trunk.

The cause of psoriasis isn’t known, but there are a number of treatment options. Possibly you’ve seen a glossy, happy ad for one of these treatments, a drug called Skyrizi. It’s been in heavy rotation and in 2020, hit number four on a top 10 list for ad spending by a drug company.

Splashing in blue water

A woman in a bathing suit sprints down a dock and jumps into the water with several friends. There’s lots of smiling and splashing. A voiceover says “I have moderate to severe plaque psoriasis. Now, there’s Skyrizi. Three out of four people achieved 90% clearer skin at four months after just two doses.”

Then, the voiceover moves to warning mode: “Skyrizi may increase your risk of infections and lower your ability to fight them. Before treatment your doctor should check you for infections and tuberculosis. Tell your doctor if you have an infection or symptoms such as fever, sweats, chills, muscle aches, or cough, or if you plan to or recently received a vaccine.”

As these warnings are delivered, we’re treated to uplifting pop music — “nothing is everything,” a woman sings — while attractive young people flail about in the water.

“Ask your doctor about Skyrizi,” a voice instructs. Did I mention a plane is skywriting the drug’s logo? I guess it’s putting the “sky” in Skyrizi.

What is Skyrizi?

Skyrizi (risankizumab) is an injectable medication that counteracts interleukin-23, a chemical messenger closely involved in the development of psoriasis. The standard dosing is two injections to start, followed a month later by two injections once a month, and then two injections once every three months.

Did you catch that “injectable” part? This is not a pill. If you missed that point while watching the commercial, it’s not your fault. The word “injection” appears once, written in faint letters at the very end of the commercial.

By the way, the FDA has only approved this drug for moderate to severe — not mild — plaque psoriasis. The studies earning approval enrolled people with psoriasis on at least 10% of their skin and two separate measures of severity.

What the ad gets right

  • The ad states that 75% of people with moderate to severe psoriasis experienced 90% clearance of their rash within four months after only two doses of Skyrizi. This reflects the findings of research studies (such as this one) that led to the drug’s approval.
  • The recommendations regarding screening for infections (including tuberculosis) and telling your doctor if you’ve gotten a recent vaccine are appropriate and should be standard practice. By lowering the ability to fight infection, this drug can make current infections worse. It may reduce the benefit of certain vaccines, or increase the risk of infection when a person gets a certain type of vaccine called a live-attenuated vaccine.

And the theme song? People with visible psoriasis often cover up their skin due to embarrassment or stigma. The rash isn’t a contagious infection or a reflection of poor health, but other people may react as if it is. So, an effective treatment could potentially allow some to forego covering up and show more skin: it means “everything” to someone suffering with psoriasis to cover “nothing.” Thus, a theme song is born.

What else do you need to know?

A few things about this ad may be confusing or incomplete, including:

  • Currently, each dose of Skyrizi is actually two injections. So, a more accurate way to summarize its effectiveness would be to say that improvement occurred within four months after four injections (rather than “just two doses”).
  • Like most newer injectable medications, this one is quite expensive: a year's supply could cost nearly $70,000. The drug maker offers a patient assistance program for people with low income or limited health insurance, but not everyone qualifies. Health insurance plans generally require justification from your doctor for medications like Skyrizi, and your insurer may decide not to cover it. Even if covered, this prior approval process can delay starting the medication, which may still be expensive due to copays and/or deductibles.
  • There is no mention of the many other options to treat psoriasis, some of which are far less costly. These include medications that do not have to be injected (such as oral methotrexate or apremilast), and UV light therapy (phototherapy). And there are other injectable medications. So, ask your doctor about the best options for you.

The bottom line

Some people appreciate the information provided by medication ads. Others favor a ban on such advertising, as is the case in most other countries. And recently, two advocacy groups asked the FDA not to allow drug ads to play music when the risks of drug side effects are presented, arguing that it distracts consumers from focusing on this important information.

Since these ads probably are not going away anytime soon, keep in mind that they may spin information in a positive light and leave out other important information altogether. So, be skeptical and ask questions. Get your medication information from your doctor or another unbiased, authoritative source, not a company selling a product.

Regardless of how you feel about medical advertising, it’s hard to hate the Skyrizi theme song. Feel free to sing along.

Embryo donation: One possible path after IVF

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For decades, in vitro fertilization (IVF) has enabled countless people to have children, often after years of disappointment. It’s a complex process, medically and emotionally. Those embarking on an IVF cycle are often laser-focused on the baby they long for. Most hope a cycle will yield several embryos, because it frequently takes more than one embryo transfer to achieve a successful full-term pregnancy.

Any remaining embryos may offer the hope of future pregnancies and additional children. Yet remaining embryos also bring difficult decisions to the fore — if not immediately, then in subsequent years. The decisions one person, or a couple, makes might be divided into five paths. One path — donating embryos to another person or couple hoping for children — carries with it many questions. This path, and those questions, are the subject of this post.

A decision pathway for people who became parents through IVF

If you became a parent through IVF and have remaining embryos, you are not alone. Estimates vary on the number of cryopreserved embryos in the United States, but it’s likely to be in the hundreds of thousands.

You may be among the many people or couples who plan to use their embryos, or among those whose family feels complete. And you may be starting to figure out what to do with your embryos, or you may be putting the decision on hold, paying for annual embryo storage and feeling no urgency to make a decision, since embryos can remain safely frozen for many years. Having “extras” in deep freeze may offer comfort, kind of a psychological insurance policy after years of disappointment and loss.

Sooner or later, though, most people find themselves at a decision point, considering these options:

  • You can discard your remaining embryos. This may feel harder than you anticipated but absolutely doable. You see these embryos as part of the IVF process that enabled you to have your cherished child or children. The word “discard” sounds harsh, but you are not prepared to parent another child and do not see donating them to others as an option.
  • You can decide to have an additional child. A larger family wasn’t what you’d planned on or hoped for, but you see extra embryos as part of IVF, and a new child as meant to be. You look at the family you have and decide it is worth undergoing at least one more embryo transfer before making a final decision to discard.
  • You can decide to donate your embryos to science. Unfortunately, if you begin to explore this, you’ll discover there is no easy route for it. Perhaps you will choose to explore other possible pathways, or decide to focus on one of the other options.
  • You can donate your embryos to another person or couple. For some, this feels natural: you have been given the gift of children and you want to pay it forward to others longing for pregnancy and parenthood. However, for many the decision to donate does not feel easy or natural. Rather, it poses a huge dilemma: you want to honor the embryos and offer them a chance at life, but you have unsettled feelings when you think of your genetic offspring being raised by another family.
  • Not to decide is to decide. In listing options, it is important to acknowledge that some of your fellow IVF parents are deciding not to decide. They are among the many who have “abandoned” their embryos (the term clinics use for families that avoid contact). They stop paying their storage fees; they fail to respond to outreach calls and letters.

What questions arise if you choose to donate embryos to another family?

Writing in TheNew York Times about facing her own decision about unused embryos, author Anna Hecker said, “For me this far surpasses discomfort. I see it as a life-or-death decision, which makes it nearly impossible to make.”Having worked with couples making this decision, I can attest that this sense of the “nearly impossible” passes over time, as people grapple with their choice and come to a place of clarity and peace.

Below are some — though not all — questions you are likely to confront as you think about donating embryos. If you are part of a couple, you can sort through these questions with your partner. (If you are single, the decision is yours to make.)

  • How would we feel about another family raising a child created with our genes?
  • Would it feel okay if we knew the family we donate to, or could that make it harder, seeing what might have been our child growing up with others as parents?
  • Is this fair to the children involved? How will our children feel knowing they have full genetic siblings in another family? What will they make of the fact that it was the random choice of an embryologist who determined which embryo would land in our family and which in another?
  • How will children who come from our donation feel? Will they feel displaced, like they landed in the wrong family? Will they, perhaps, feel a bit like a science-fiction project?
  • How will we feel about possible challenges in the future: our child gets sick, the family we donate to gets divorced, we fervently disagree with the parenting style and values of the other family?
  • If we decide to donate, how should we go about finding a family? Does geography or demographics matter — for example, will it feel good or more complicated to have them nearby? Should we donate to a same-sex couple, an older single woman, or others?
  • Do we want to tell family members and friends of our decision to donate our embryos? If so, how much do we share of this information?
  • If there are several embryos, do we donate all to the same family or divide them? For those who feel strongly about not wanting to discard embryos, it may be important to ensure that none are discarded when the receiving family feels complete.
  • If our embryos were created with the help of donor eggs and/or sperm, should we seek permission or approval from the donor? How do we go about this if we do not have access to the donor?

These questions are complicated, best made over time and with care. While you may want to make the decision soon so that you can feel closure and move on as a family, I have found this is one instance in life when moving slowly, visiting and revisiting a decision, accepting doubt and the need to take pauses, all contribute to you eventually feeling the rightness of your decision.

Recent study shows more complications with alternative prostate biopsy method

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If a screening test for prostate cancer produces an abnormal result, the next step is typically a biopsy. In the United States, this is almost always done by threading a biopsy needle into the prostate through the rectum. By watching on an ultrasound machine, doctors can see where the needle is going. Called a transrectal ultrasound (TRUS) biopsy, this procedure comes with a small but growing risk of infections that are in turn increasingly resistant to current antibiotics.

To minimize infection risk, doctors can also thread the biopsy needle through a patch of skin between the anus and scrotum called the perineum, thus bypassing rectal bacteria. These so-called transperineal (TP) biopsies offer a further advantage in that they provide better access to the tip (or apex) of the prostate, which is where 30% of cancers occur. However, they are also more painful for the patient. Until recently, they were done only in hospital operating rooms under general anesthesia.

Today, technical advances are making it possible for doctors to perform TP biopsies under local anesthesia in their own offices. And with this development, pressure to limit infections by adopting this approach is growing.

During a recent study, Harvard scientists looked at how the two methods compare in terms of cancer detection and complication rates. In all, 260 men were included in the study, each closely matched in terms of age, race, prostate-specific antigen levels, and other diagnostic findings. Half the men got TRUS biopsies and the other half got TP biopsies, and all the procedures were performed at a single medical practice between 2014 and 2020. Per standard clinical protocols, all the men in the TRUS group took prophylactic antibiotics to prepare. By contrast, just 43% of men in the TP group took antibiotics, in accordance with physician preferences.

Results showed minimal differences in the cancer detection rate, which was 62% in the TP group and 74% among men who got TRUS biopsies. But importantly, 15% of men with cancer in the TP group had apex tumors that the TRUS biopsies "may have missed," the study authors wrote.

More complications with the TP approach

As far as complications go, one man in the TRUS group developed an infection that was treated with multiple rounds of oral antibiotics. None of the TP-biopsied men got an infection, but eight of them had other complications: one had urinary blood clots that were treated in the hospital, two were catheterized for acute urinary retention, three were medically evaluated for dizziness, and two had temporary swelling of the scrotum.

Why were the TP noninfectious complication rates higher? That's not entirely clear. For various reasons, doctors wound up taking more prostate samples (called cores) on average from men in the TP group than they did from men in the TRUS group. The authors suggest if an equivalent number of cores had been taken from men in either group, then the complication rates might have been more similar. (In fact, larger comparative studies performed in hospital-based settings show no difference in complication rates when equal numbers of cores are obtained). But doctors in the current study also had more experience with TRUS biopsies, and that might also explain the discrepancy, the authors suggest. And as doctors in general become experienced with the TP method, complication rates might fall.

In an editorial comment, Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, editor of the Harvard Health Publishing Annual Report on Prostate Diseases, and editor in chief of HarvardProstateKnowledge.org, acknowledged positive findings from the study, particularly a reduced need for antibiotics with the TP method, and the discovery of apex tumors TRUS biopsies could have missed. Garnick also highlighted a "steep learning curve" with TP biopsies, and how some of the noninfectious complications required hospital-based care. "The ability to perform TP biopsies in an office setting should enable future comparisons with TRUS to help answer whether this new TP technology has enduring value," he wrote.