A skeptical look at popular diets: The lowdown on low carb

In the seventh post in the series A Skeptical Look at Popular Diets, physician Randall Stafford examines down the pros and cons of a low-carb diet.

By Randall Stafford

As the name implies, this diet reduces dietary carbohydrates, including many common foods that contain sugars and/or starches. To make up for this reduction, the intake of protein and fat can increase. Frequently, however, low-carb dieters do not fully replace the calories from reducing carbs and they lose weight as a result.

This diet has several favorable features, but a high intake of animal-based saturated fats can offset the benefits. One version, the Atkins Diet, was promoted to facilitate weight loss. A problem with interpreting “low carbohydrate” is that there is no consensus on how low is “low.”

Health rationale slogan: Restricting carbs helps you lose weight and solves many metabolic problems.

Analysis: Depending on how low carb you go, a lower carb diet potentially restricts multiple common foods including grains, legumes, fruits, breads, desserts, pastas, and starchy vegetables. Particularly off-limits: processed foods made with flour and added sugars. Food sources higher in protein and fat take their place, such as meats, eggs and nuts.

The diet’s potential benefits are many, including helping reverse insulin resistance, an early stage in the development of type 2 diabetes. It does this by restoring normal carbohydrate processing. By restricting carb intake, the body no longer has to cope with a large, sudden influx of sugar into the bloodstream. In addition, people following this diet may experience less hunger when they restrict calories, which facilitates weight loss (at least in the short term).

Stanford nutrition scientist Christopher Gardner, PhD, studied longer term weight loss and demonstrated similar favorable benefits from a lower carb vs. a lower fat diet when both approaches focused on healthy choices.

The food sources that are low carb range widely in healthfulness. For example, meat has no carbohydrates, but if meat intake is increased to replace carbohydrates, this can boost unfavorable saturated fats. Interestingly, in Gardner’s weight loss study, the group that followed a healthy low-carb diet had no adverse metabolic effects. This group decreased overall calories almost solely by restricting carbohydrate-rich foods, without substantially increasing protein or saturated fat intake.

If the carbohydrate restriction goes beyond added sugars and refined grains, to the point of restricting vegetables, whole grains and beans/legumes, this can result in vitamin and mineral deficiencies. And, if carb intake is low enough, ketosis can occur with its accompanying nausea, headache, physical and mental effects, and bad breath. Additionally, carbohydrate-rich foods are the primary sources of fiber, and low-fiber diets increase the risk of colon cancer and may have adverse effects on the gut microbiome.

Easy to follow?: Depending on how severe the carbohydrate restriction, this diet can be difficult to follow because it can dramatically restrict the intake of most of the major food groups, including fruits, beans/legumes, grains, starchy vegetables, and dairy.

Dominant source of protein: Animal proteins such as meat and eggs, which don’t contain carbs (unlike protein-rich legumes and grains).

Most common fats: Oils and saturated fats from meat.

What about carbs?: Limited carbs, but some variations of this diet can include potentially good carbs found in fibrous vegetables and beans/legumes.

When it goes wrong: Emphasizing meat consumption can lead to problems. High intake of the saturated fats found in meat may increase the risk of future heart disease and cancer. This harm would be greatest from emphasizing fatty red meats (steak, bacon, etc.) or processed meats, as opposed to leaner meats, such as poultry.

To make it healthier: The potential health benefits of lower carb diet can be maximized by focusing primarily on eliminating added sugars and refined grains, and emphasizing sources of fat from plant sources (e.g., olive oil, nuts, avocados), from fatty fish (e.g., salmon), or from lean meats.

Variations: The Atkins diet emphasizes restricting carbs, but allows as much fats and protein as desired. If carbohydrates are severely restricted, a low-carb diet becomes a ketogenic diet.

If you’re going to cheat: Including beans/legumes may make sense because their more complex starches and fiber differ from the simple starches in processed grains and starchy vegetables. Eating these foods provides a much greater range of possible foods, making the diet easier to follow.

Conclusion: A lower carb diet can offer weight loss and metabolic improvements. In its extreme forms where all starchy vegetables, bean/legume, fruit, and grain intake is restricted, it is difficult to follow and has the drawback of high saturated fat and low fiber intake.

Nonetheless, this diet could be a good starting place for initiating weight loss when the focus is on minimizing added sugars and refined grains, and maintaining or even increasing fibrous vegetables.

This is the seventh post in a series called A Skeptical Look at Popular Diets. The series will review the eight currently most prominent diets in America. The next blog post will discuss low-fat diets.

Randall Stafford, MD, PhD, is a professor of medicine at Stanford. He practices primary care internal medicine and studies strategies for preventing chronic disease. Stanford professor and nutrition scientist Christopher Gardner, PhD, examines the impact of diet on health and disease. Min Joo Kim provided research assistance.

Photo by Jakub Kapusnak

Once uninsured, a medical student — and her peers and mentors — are giving back

In this Stanford Medicine Unplugged post, medical student Yoo Jung Kim reflects on how being uninsured has inspired her to provide care for others.

By Yoo Jung Kim

I’m constantly awed by the fact that I get to be part of one of the best hospitals in the world, especially because as a kid, I grew up without health insurance.

These were the days before the Affordable Care Act; there was no penalty for going without health coverage. As a non-citizen, I was ineligible for Medicaid, and private health care was prohibitively expensive for my family. Fortunately, I was a healthy kid with a robust immune system, and I never had to go to the doctor’s office except for mandatory school physicals and vaccinations. When I rotated through my pediatrics rotation, I was struck by how many well-child visits that I had unknowingly missed.

But not having insurance meant that when my family had to pay, we paid big time. When I was in high school, my otherwise healthy dad developed an acute infection — just a stroke of terrible luck. He was whisked away in an ambulance, evaluated in the emergency room, and admitted to the hospital.

Fortunately, he made a full recovery, but the financial costs of the ambulance ride, the expertise of numerous medical providers, and the medications, were astronomical. It took months to negotiate the bill with the numerous parties — hospitals, physician groups, diagnostic services — that had contributed to his care. On the advice of a patient financial counselor, I wrote letters to various offices to beg for discounts. Fortunately, many recipients acquiesced, but even so, it took years to pay off the bills.

From this experience, I got the sense that health care was a privilege for those with the means to pay for it, like a good union or white-collar job. In a way, it sparked my interest in medicine because I wanted to be a doctor to those who needed my services the most.

So far, I’ve been able to pursue this goal at Stanford. I’m starting my third year as a specialty clinic coordinator at Arbor, one of two free medical clinics run by Stanford students under the guidance of residents and attendings who graciously volunteer time out of their busy schedule.

Even after the implementation of the ACA, the clinic’s waiting room is packed with people wanting to be seen. Some of our patients are undocumented residents who are ineligible for Medicaid or Medicare. Others are elderly parents of savvy graduate students and postdoctoral fellows visiting from developing countries for a rare opportunity to see their children and get care from U.S. physicians. Then there are people who are just down on their luck or between jobs and haven’t been connected to the social services available to them.

At the specialty clinic that I co-manage, I receive referrals from the general free clinic, call patients to make appointments, organize student and physician volunteers, and arrange supplies for various in-clinic procedures. I’ve seen students and physicians help underserved patients by treating illnesses, preventing downstream consequences of chronic conditions, and coordinating a care plan to make sure that patients can get the follow-up that they need.

It is a team effort: The amazing attendings have volunteered for years to help patients and teach trainees, and the residents ensure one of their own is present to help every clinic date and that our supply closet is appropriately stocked. The medical students learn more about the specialty from the attendings and the residents, and, most importantly, patients get the care they need.

Some patients have been harboring their illnesses for years, using folk remedies or over-the-counter medications to treat their symptoms instead of going to see a physician. An ounce of prevention may be worth a pound of cure, but I understand their rationale because the same thing kept me awake at night as a kid: what if the doctors find something wrong with me or my parents, how will we be able to pay for the treatment? Maybe it’s better not knowing, but what if the condition gets worse and becomes more difficult and expensive to treat? How will we pay for the treatment?

Now that I have insurance and have more flexibility with my schedule during my research gap year, I’m finally catching up on my health, including well-woman’s exams, recommended vaccinations, minor surgeries, and dental check-ups. I’m acutely aware of how lucky I am that I can get care and follow-up from incredible Stanford providers, some of whom I’ve worked with before (this is admittedly a bit awkward, but that’s a story for another time), but many others still struggle to access even the most basic medical services.

Growing up without health insurance helped me to understand the plight of many individuals who still face similar challenges, and as a medical student, I am awed and inspired by the physicians at Stanford who make time out of their busy schedules to help the underserved.

Stanford Medicine Unplugged is a forum for students to chronicle their experiences in medical school. The student-penned entries appear on Scope once a week during the academic year; the entire blog series can be found in the Stanford Medicine Unplugged category.

Yoo Jung Kim is a fourth-year Stanford medical student and the co-author of What Every Science Student Should Know, a guide for aspiring college STEM students. She also writes for Doximity and U.S. News and World Report.

Image by Tumisu

At event, experts talk heart health and share the latest on Apple Heart Study

If you happened to have dropped by the Apple Store in downtown San Francisco Monday evening, you might have caught sight of something out of …

By Michelle Brandt

If you happened to have dropped by the Apple Store in downtown San Francisco Monday evening, you might have caught sight of something out of the ordinary. Under the direction of an enthusiastic woman with a tight bun in her hair and a huge smile, dozens of people on the second floor of the bright, airy store suddenly stood up and began squatting and marching — and two people even hit the floor to demonstrate a push up and plank.

The crowd was there for a free special program called Heart Health with Apple, and long-time celebrity trainer Jeanette Jenkins had encouraged attendees to try a few moves. She was part of a panel of health, tech and fitness experts brought together to discuss heart health, share practical tips and describe how the Apple Watch is being used to shed light on heart disease.

Before the audience was prompted out of their seats by Jenkins, panel moderator Julz Arney, with Apple Fitness Technologies, posed some important questions to the experts at hand. Bob Harrington, MD, a Stanford cardiologist and president-elect of the American Heart Association, took the mic first to remind the audience that heart disease is the number one killer in the world and explain there’s a growing awareness of the seriousness of the problem, especially among women. He also noted that an increasing number of patients have come to him over the years with their own health data — something he says empowers patients and “allows physicians to partner with them.”

Much of that data comes from wearables, and Harrington and fellow panelist Sumbul Desai, MD, a practicing physician at Stanford and VP of Health at Apple, spent a chunk of time at the event discussing the data being captured through the Apple Heart Study. That study, which was launched by Stanford in collaboration with the company last year, is exploring whether an app on the Apple Watch that analyzes pulse rate data can identify a potentially deadly heart disease called atrial fibrillation.

The Apple Heart Study is the largest study ever done on the disease — which is characterized by an irregular heartbeat and can increase the risk of stroke and heart failure — with more than 400,000 participants enrolled. “I’ve been doing clinical trials for 30 years, and having 5,000 participants is considered a big study,” said Harrington in explaining the scope of this research. The ability for researchers to reach this many people, he said, shows “the power of new technology.”

The researchers hope to glean much information from the study, including, Harrington said, details on how often atrial fibrillation occurred among this population and how exactly study participants and their physicians used the technology. For example, did participants who received an irregular pulse notification on their watch go on to seek medical attention?

The study is in its final phase of data collection, and initial results will be released at the American College of Cardiology conference in New Orleans next month. Desai, for one, is excited. “I went to medical school to make an impact,” she said. “And to be able to do this at scale” is rewarding.

Before ending their session, Arney and the panelists made the point of encouraging attendees to tend to their hearts and overall health well before there’s a problem. Harrington shared the AHA’s recommendation of walking for 30 minutes a day for five days a week, and Jenkins offered “practical and tactical tips” for the audience: Add exercise to your to-do list on a weekly basis; choose a work-out program that can easily be done, even in your living room; and, if you’re a parent, involve your kids. Desai’s advice was even simpler: “Just move.”

Photo by Michelle Brandt

About the future: A look at the Pediatric Innovation Showcase

Experts came to Stanford for the Pediatric Innovation Showcase to learn about many approaches to helping children’s health, from social media to surgery.

By Erin Digitale

Scientists, innovators, venture capitalists and medical industry experts gathered at Stanford last week for the second annual Stanford Children’s Health Pediatric Innovation Showcase, a daylong event highlighting new devices and developments in pediatric medicine.

The conference covered wide ground, including engaging patients with social media, better hospital design, commercialization of scientific innovations, the promises of gene therapy, and several medical uses of virtual reality. Capping the day, pediatric health innovators vied for funding in a pitch competition hosted by the UCSF-Stanford Pediatric Device Consortium. Of 80 entries, 13 finalists described the medical devices they are developing for babies and kids.

Lloyd Minor, MD, dean of the School of Medicine, welcomed participants by highlighting Stanford’s culture of collaboration. For example, nearly a third of Stanford engineering faculty are currently conducting research with medical applications, he said. “It’s because that’s where the really interesting problems are today,” Minor said.

At the same time, innovation in pediatric medical devices lags behind those for adults, he noted. “The consortium’s mission to ensure that the latest technologies are available to all — in this case our youngest patients — mirrors that of Stanford Medicine’s precision health vision.”

Paul King, president and CEO of Stanford Children’s Health, offered uplifting opening remarks. “Pediatric medicine at its core is about optimism — it’s about the future.”

Social media and other online tools have great power to provide parents with evidence-based information about pediatrics, keynote speaker Wendy Sue Swanson, MD, told the audience. Swanson, chief medical officer of Before Brands and chief of digital innovation at Seattle Children’s Hospital, writes a pediatrics-focused blog, Seattle Mama Doc, and uses many other channels to reach out to parents.

“Communication may be your most important technology,” Swanson told the audience. “Are you making information online to contribute to something better?”

Swanson shared several stories from her work. Her most popular blog post, Toddler Sleep: 4 reasons toddlers wake up at night, covers a topic from the bread and butter of well-child pediatrician visits. Why was it so widely read?

Swanson said she found an answer in data on her readers’ engagement with the post. When it was midnight in Seattle, views were peaking there; when it was midnight in Singapore or India, that was where readership was highest. Parents want just-in-time information, and pediatricians need to help ensure that what parents find online is medically accurate, Swanson said.

Similarly, doctors need to make sure that families can get scientifically accurate information about subjects like vaccines, no matter when or where they look for it. Recently, Swanson has worked with Seattle Children’s to build a tool called Flu Doctor that answers basic questions about flu vaccines via Alexa. Swanson wants more doctors to join such efforts to counteract anti-vaccine propaganda and anecdotes that proliferate online.

“If you don’t do it, someone’s going to confuse your expertise with someone else’s experience,” she said.

At the end of a day, teams vied for about $300,000 during a pitch competition. The three platinum awards were given to:

  • Bionic Tot, for its Button Huggie, a device for children with gastronomy tubes, which helps prevent infections, leaking and skin breakdown at the tube’s external site.
  • Gravitas Medical, for its sensor-enabled nasogastric feeding tubes. The sensors guide placement of the tubes and warn caregivers if tubes end up in the esophagus or lung instead of the stomach.
  • Palmm, for its bio-electronic glove that provides low levels of electrical stimulation to stop excessive sweating in patients’ hands.

Photos courtesy of Stanford Children’s Health

New algorithm could accelerate diagnosis of genetic diseases using clinical records

By Helen Santoro

In a continued effort to speed up the diagnostic process of severe genetic diseases, Stanford’s Gill Bejerano, PhD, and his colleagues have developed a new algorithm that can quickly locate important disease-related information within a patient’s medical record.

In a paper recently published in Nature Genetics in Medicine, Bejerano and Cole Deisseroth, a Bio-X undergraduate fellow, along with researchers including Johannes Birgmeier, a graduate student in computer science, developed an algorithm that scans through records of patients and extracts the patient’s key phenotypes, or observable traits.

The team focused particularly on patients with life-threatening genetic diseases such as sickle cell anemia, cystic fibrosis and Huntington’s disease. Manually scanning through patient notes without a computer, a dedicated clinician can process around 200 patient records in a 40-hour work week, the researchers said. This algorithm can do the same job in 10 minutes, further saving busy doctors an additional three to five hours per every downstream disease diagnosis.

“A diagnosis is extremely valuable for the patient, for the family and for the attending clinician,” said Bejerano. But finding the diagnosis within the patient’s genome is very time consuming and, “for that we need computational tools.”

The algorithm is called ClinPhen — a combination of “clinical” and “phenotypes.” After examining a patient’s medical records, the algorithm parses the sentences into short phrases. For example, if the clinical note reads, “The child has short stature and long eyelashes. She has a cleft palate and a small jaw,” the phrases, “The child has short stature”, “and long eyelashes”, “She has a cleft palate”, and “a small jaw” would be selected.

These phrases are converted into codes from an existing phenotype database called the Human Phenotype Ontology, or HPO. The codes are then sorted, with the most- and earliest-mentioned phenotypes at the top of the list. ClinPhen can also identify words, such as “father” and “does not have” and not associate any phenotypes mentioned in that sentence with the patient.

ClinPhen’s accuracy, phenotype filter and speed was validated using six sets of real patient clinical notes from four different medical centers. When compared to other phenotype extraction algorithms, ClinPhen was more precise and 20 times faster, the research showed.

“ClinPhen actually guesses slightly better than a clinician,” Bejerano said. “We can capture clinician intuition and pick the right set of phenotypes to best facilitate the diagnosis.”

The HPO codes produced by ClinPhen will then be fed to Phrank, another algorithm designed by Bejerano and his colleagues that ranks patients’ genes that have rare variants for their ability to explain the phenotypes, or traits, identified by ClinPhen.

Bejerano describes the efforts as a “computational ecosystem”, and said he hopes to see this ecosystem implemented in clinical settings soon.

“The medical establishment is very conservative. And for good reason… You want to protect the patient,” Bejerano said. “[But] I think that slowly, very slowly, there is a shift towards using more of these automated systems. With 60 million patients to be sequenced in the next several years, we simply have no choice.”

Image by Darryl Leja, NHGRI

Originally published at scopeblog.stanford.edu on December 5, 2018.

“Mitotic catastrophe” describes how aged muscle stem cells die, and provides clues to keeping them healthy

By Krista Conger

As a parent, I chuckled a bit when I first heard the term ‘mitotic catastrophe.’ The phrase describes a situation in which cells attempting to divide bungle the complicated maneuver and die an ignominious death. Even cells, it seems, sometimes find that the attempt to create happy, functional offspring is fraught with peril.

But, joking aside, the death of dividing cells — aka mitotic catastrophe — can have serious consequences, particularly when those cells, namely stem cells, are responsible for regenerating new muscle in response to injury or aging.

Now neurologist Thomas Rando, MD, PhD, together with senior research scientist Ling Liu, PhD, and pathologist Gregory Charville, MD, PhD, have pinpointed mitotic catastrophe as a cause of death of old muscle stem cells. These cells are less able than their younger counterparts to repair muscle damage. They’ve also shown that this “death by dividing” is the result of a malfunction of the cross-talk that occurs between the stem cells, nestled along the lengths of muscle fibers, and their neighboring cellular support team known as the stem cell niche.

They recently published their work in Cell Stem Cell.

As Rando explained in an email to me:

Mitotic catastrophe has primarily been described in the scientific literature as a way that cancer cells die, especially after treatment with chemotherapeutic agents. So it was a surprise to us to see the old muscle stem cells dying in this way. In fact, prior to this research, I had not even heard the term mitotic catastrophe.

In contrast, younger muscle stem cells usually divide without issue when called upon to do so, the researchers found.

Further investigation revealed that the catastrophic death of the aged muscle stem cells is related to a reduction in the amount of a protein called p53 in the cells. p53 is a well-known tumor suppressor that normally works to pause the division of cells with DNA damage to allow them the necessary repair time. When p53 is mutated, damaged cells continue dividing and sometimes become cancerous.

The researchers went on to discover that the decline in p53 is due to a reduction in the activity of a biochemical signaling cascade called the Notch pathway, which is activated in the stem cells by signals produced by neighboring cells. This close relationship between the stem cells and their niche has been shown by Rando and others to be vital in maintaining the function of stem cells.

As Rando explained:

Increasing evidence points to the cross-talk between stem cells and their niches as being essential to maintain normal tissue homeostasis and repair. If one disrupts the stem cells or the niche cells, these processes are impaired.

Some stem cells persist in a quiescent state for years or even decades, and normal structure and function of the stem cell-niche unit appears to be essential for such long-term cell, tissue, and even organismal survival.

Because DNA damage accumulates with age, Liu, Charville and Rando wondered whether it was possible to avert mitotic catastrophe in the aged stem cells by treating them with a drug that increases p53 expression — perhaps by giving them breathing room to repair the damage before dividing. Indeed, they found that boosting p53 expression in the stem cells allowed them to divide more successfully improved their ability to repair muscle damage.

Rando and his colleagues are now keen to learn whether intervening in this natural aging process of the stem cells and their niche can lead to therapies that can help old muscles, and potentially other tissues and organs, heal more quickly and efficiently.

As Rando said:

We want to know why Notch signaling declines in the muscle stem cell compartment with age. This could suggest another potential therapeutic approach to preventing mitotic catastrophe in aged muscle injury. And we would like to know whether these findings represent a general phenomenon in aged stem cell populations.

Photo by ChangGp

Originally published at scopeblog.stanford.edu on October 4, 2018.

The lifespan of people over 65 in developed areas is increasing

Stanford study finds the lifespan of people over the age of 65 in developed countries is steadily increasing and is showing no signs of slowing down.

By Holly MacCormick

When it comes to milestone birthdays ages 18, 21, 40, 50, 75 and 100 seem to get all the glory, but now a Stanford-led study suggests that reaching the age 65 is cause for extra celebration.

Stanford biologist Shripad Tuljapurkar, PhD, and a team of Stanford researchers found that people over the age of 65 in developed countries will live, on average, about six years more than their grandparents did.

This result was not expected.

Tuljapurkar and his colleagues were curious to know whether people are approaching a limit to human lifespans, and if so, are there factors that enable some people to live longer than others.

To find out, they examined a 50-year dataset of birth and death records. These longevity records included people living in 20 different developed countries between 1960 to 2010.

Tuljapurkar suspected that humans were approaching the upper bound of their lifespan, but the data revealed a different scenario. Tuljapurkar explained the findings of their study in a recent Stanford news story saying:

The data shows that we can expect longer lives and there’s no sign of a slowdown in this trend. There’s not a limit to life that we can see, so what we can say for sure is that it’s not close enough that we can see the effect.

The results showed that the average death date for people living beyond the age of 65 increased by three years in every 25-year period. As the researchers write in their paper, this trend is noteworthy because of its “surprising regularity.”

One might think that a certain decade would be unusually good or bad for survival, or that particular medical advancements had a big effect on human longevity.

Instead, the trend of increased lifespan is consistent across all decades in the study, for males and females, in all 20 countries, and there was no significant increase in longevity from any particular medical breakthrough.

So, what’s helping people over the age of 65 live longer?

According to this study, it’s not yet clear. No single biological factor was found that seemed to give certain people the ability to live longer than others. Even wealth didn’t seem to confer a significant survival benefit — at least not for people over the age of 65.

“As someone who would like to be a one-percenter but is not,” Tuljapurkar quipped, “I’m certainly very happy to know that my odds of getting to live longer are just as good as the millionaire down the street.”

Photo by Pexels