Dr. Bray Links

Friday, April 28, 2017

Geisinger CEO: U.S. Healthcare Needs a Good Shakeup

The U.S. healthcare industry could use a good shaking up, a healthcare executive said here Tuesday.

"I think our industry is so screwed up and it's ripe to be disrupted," David Feinberg, MD, MBA, president and CEO of Geisinger Health System in Danville, Pa., said at a conference sponsored by the Duke Margolis Center for Health Policy and the consulting firm McKinsey & Co. "Either we do it or some Stanford dropout in a black turtleneck is going to."

"Can we take care of people in a way that's dignified, that's culturally sensitive?" he asked. "Can they afford it? Is it easy to get? Is it something you want for your own family? Let's focus on high value, great experience, and low costs."

On the other hand, many of the problems with the healthcare system today are really public health problems and aren't something that private insurers can readily fix, said J. Mario Molina, MD, president and CEO of Molina Healthcare, a managed healthcare company based in Long Beach, Calif. "Obesity is not something you're going to cure; it's a public health issue. ... We really can't expect health plans to [take care of] that."

"We try to do something about obesity, but it's really difficult from a health plan, medical model," he continued. "We're really good at covering acute illnesses or managing chronic ones [but for conditions like obesity] it doesn't work well. We need to invest more in public health; if we did that, we wouldn't invest as much in healthcare per se."

But Feinberg disagreed: For example, "We take diabetics who are food insecure and say, 'Here's food for the whole week for you and your family' -- every week. We've seen decreases in hemoglobin A1c in every single patient, decreases in weight, decreases in blood pressure ... if this was a pill it would be a miraculous pill. We've had patients we had spent $220,000 in 4 years before we started giving them food; in the year they've been in the program, our medical cost is $1,200. Hippocrates talked about food as medicine a long time ago; I think we've lost our way."

Sometimes solving healthcare problems calls for breaking the rules, he continued. "When I got to Geisinger a couple of years ago, there were providers we were spending $500,000 a year on for visits, and the only thing they did was prescribe opiates. They weren't even in our network." But when Feinberg wanted to stop using them as providers, he was told he couldn't cut them off without going through a laborious process to do so.


Does Parkinson's disease begin in the gut?

They say that "what happens in Vegas stays in Vegas." But this is definitely not true of the vagus nerve, which wanders from the stomach to the brain, passing through the heart, esophagus and lungs along the way.

A new study offers fresh support for an intriguing theory about the vagus nerve's role in Parkinson's disease, a neurological disorder that causes tremors, gait difficulties and sometimes dementia in roughly 1 million Americans and as many as 10 million people worldwide.

This theory suggests the vagus nerve may be more than a highway for signals to travel to the brain from the many organs it touches. It may also be the conduit for transporting the protein alpha-synuclein from the stomach to the brain, where it forms telltale clumps in Parkinson's sufferers.

If true, this theory would pinpoint a possible origin of the degenerative brain disorder — in the gut. It would also confirm the centrality of this mysterious protein, whose precise role in Parkinson's is not well understood.


Chronic fatigue syndrome linked with differences in gut bacteria | Fox News

People with chronic fatigue syndrome may have imbalances in their gut bacteria, a new study suggests.

The study found that people with chronic fatigue syndrome had higher levels of certain gut bacteria and lower levels of others compared to healthy people who didn't have the condition.

The researchers then checked to see if these imbalances also characterized the subset of patients in the study who had irritable bowel syndrome (IBS), an intestinal disorder that is common in people with chronic fatigue syndrome. Results showed that patients did indeed have different patterns of gut bacteria disturbances depending on whether they had only chronic fatigue syndrome or both chronic fatigue syndrome and IBS.

The findings suggest that researchers may be able to divide chronic fatigue syndrome patients into different groups depending on their gut bacteria imbalances, which could aid in the diagnosis and treatment of the disease, the researchers said. 


What The Health

Tick bites that trigger severe meat allergy on rise around the world

Cases of the emergent allergy have been reported in Europe, Asia, Central America and Africa, but it is most prevalent – and on the rise – in parts of Australia and the United States where ticks are endemic and host populations are booming.

Bandicoots and other small native mammals are flourishing along the east coast where the Australian paralytic tick is endemic.

The Lone Star tick is widespread throughout the US, but meat allergies have been reported in the south-eastern states, home to growing herds of white-tailed deer.

But tick bite-induced anaphylaxis – the most acute allergic reaction, which can result in death – is rare in countries other than Australia. Around Sydney’s northern beaches, where ticks are common, it is reportedly as prevalent as peanut allergies.

Meat allergies are exceedingly rare in adults who have not been bitten by ticks.

The link was first reported in November 2007 by Sheryl van Nunen, a clinical immunology specialist at the Royal North Shore hospital in Sydney.

Van Nunen told Guardian Australia that she had observed the association “some years before” 2007. She now diagnoses one to two patients every week.

Jana Pearce was diagnosed with mammalian meat allergy by Van Nunen after suffering an anaphylactic shock in May 2010. She had been bitten by a newly hatched tick 10 days before and had developed a “massive” rash.

Thursday, April 27, 2017

Teens Most Susceptible to Endocrine Disruption From Chemicals

Adolescents aged 12 to 21 years are two to three times more sensitive than the general population to common environmental contaminants that can disrupt thyroid function and therefore should have the latter checked, according to US researchers.

The thyroid-blocking effects of exposure to three common environmental contaminants — perchlorate, thiocyanate, and nitrate — also appear to be different in boys and girls, say Jenica McMullen, New York University School of Medicine, New York, and colleagues in their report published online April 20 in the Journal of Clinical Endocrinology and Metabolism.

Perchlorate, thiocyanate, and nitrate all inhibit the function of sodium-iodide symporter (NIS) in thyroid follicular cells at levels currently found in the environment, they point out. NIS function is key to thyroid-hormone synthesis, and disruption is a leading cause of hypothyroidism.

In adolescents, disruptions of normal thyroid function can profoundly affect every organ system, including cognitive and cardiac function, bone strength, and metabolism. Clinically, this can present as declining growth rates and changes in academic performance, including poor attention, the researchers say.


Saturday, April 22, 2017

Piloting a Remission Strategy in Type 2 Diabetes

At 8 weeks, 50.0% of the 8-week intervention group versus 3.6% of controls achieved normoglycemia on therapy (RR 14.0, 95% CI 1.97-99.38), and at 16 weeks, these percentages were 70.4% in the 16-week group and 3.6% in controls (RR 19.7, 2.83-137.13). Twelve weeks after completion of the intervention, 21.4% of the 8-week group compared to 10.7% of controls (RR 2.00, 0.55-7.22) and 40.7% of the 16-week group compared to 14.3% of controls (RR 2.85, 1.03-7.87) met HbA1C criteria for complete or partial diabetes remission.


Thursday, April 20, 2017

Are Flame Retardants Driving Some of Thyroid Cancer Increase?

Initial research suggests that some flame retardants, used in many furnishings in the home, could be associated with an increased risk of papillary thyroid cancer, the most common form of this type of cancer.

Reporting the findings at the ENDO 2017: The Endocrine Society Annual Meeting today, Julie Ann Sosa, MD, of Duke University Medical Center, Durham, North Carolina, said: "What's really novel about this study is that it's the first time we've seen a signal like this, but it should just be seen as a first study. We really need to do additional research, to understand mechanisms…and to validate our findings."


Even Short-term Oral Steroids Carry Serious Risk

Within 30 days of initiating these drugs, even at relatively low doses, users had a nearly twofold increased risk for fracture, a threefold increased risk for venous thromboembolism, and a fivefold increased risk for sepsis.

"Greater attention to initiating prescriptions of these drugs and monitoring for adverse events may potentially improve patient safety," write Akbar K. Waljee, MD, an assistant professor of gastroenterology at the University of Michigan in Ann Arbor, and colleagues. They present their findings in an article published April 12 in the BMJ.


Experts excited by brain 'wonder-drug' - BBC News

Since 2013, the research group has tested more than 1,000 ready-made drugs on nematode worms, human cells in a dish and mice.

Two were shown to prevent both a form of dementia and prion disease by stopping brain cells dying.

Prof Mallucci told the BBC News website: "Both were very highly protective and prevented memory deficits, paralysis and dysfunction of brain cells."

The best known drug of the pair is trazodone, which is already taken by patients with depression.

The other, DBM, is being tested in cancer patients.

Prof Mallucci said: "It's time for clinical trials to see if there's similar effects in people and put our money where our mouth is.

"We're very unlikely to cure them completely, but if you arrest the progression you change Alzheimer's disease into something completely different so it becomes liveable with."

But, although trazodone is a current medication, she added: "As a professional, a doctor and a scientists, I must advise people to wait for the results." 


Saturday, April 15, 2017

Gut bacteria compound may help to prevent type 2 diabetes - Medical News Today

The participants fell into two groups. One group developed type 2 diabetes within 5 years, and the other group did not develop type 2 diabetes during the 15 years of follow-up.

When the researchers compared the metabolite profiles of the two groups, they found that what stood out was differences in levels of indolepropionic acid and certain lipid metabolites.


Wednesday, April 12, 2017

Ototoxicity - Tetracyclines

Antibiotics in the aminoglycoside class, such as gentamicin and tobramycin, may produce cochleotoxicity through a poorly understood mechanism.[8] It may result from antibiotic binding to NMDA receptors in the cochlea and damaging neurons through excitotoxicity.[9]Aminoglycoside-induced production of reactive oxygen species may also injure cells of the cochlea.[10] Once-daily dosing[11] and co-administration of N-acetylcysteine[12] may protect against aminoglycoside-induced ototoxicity. The anti-bacterial activity of aminoglycoside compounds is due to inhibition of ribosome function and these compounds similarly inhibit protein synthesis by mitochondrial ribosomes because mitochondria evolved from a bacterial ancestor.[13] Consequently, aminoglycoside effects on production of reactive oxygen species as well as dysregulation of cellular calcium ion homeostasis may result from disruption of mitochondrial function.[14


Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models

However, the wide range of direct effects of tetracycline use has not been fully appreciated. We show here that these antibiotics induce a mitonuclear protein imbalance through their effects on mitochondrial translation, an effect that likely reflects the evolutionary relationship between mitochondria and proteobacteria. Even at low concentrations, tetracyclines induce mitochondrial proteotoxic stress, leading to changes in nuclear gene expression and altered mitochondrial dynamics and function in commonly used cell types, as well as worms, flies, mice, and plants. 


Monday, April 10, 2017

Mycoplasma - Wikipedia

Other species of Mycoplasma other than those listed below have been recovered from humans, but are assumed to have been contracted from animals. These use humans as the primary host:

    M. amphoriforme
    M. buccale
    M. faucium
    M. fermentans
    M. genitalium
    M. hominis
    M. lipophilum
    M. orale
    M. penetrans
    M. pirum
    M. pneumoniae
    M. primatum
    M. salivarium
    M. spermatophilum[8]


Thursday, April 6, 2017

More than 20 percent of US adults have 'high-risk' HPV

About 1 in 5 U.S. adults under age 60 is infected with a "high-risk" strain of genital human papillomavirus (HPV) that increases the risk of cancer, according to a new report.

For the report, researchers analyzed information from a nationally representative sample of Americans ages 18 to 59 who took part in a health survey from 2013 to 2014. As part of the survey, the participants underwent a physical exam in which they swabbed their genitals, and these samples were tested for DNA from 37 different types of HPV. Fourteen of these HPV types are known as high-risk strains because they are linked with an increased risk of certain cancers, including cancers of the cervix, vagina, vulva, anus, penis and throat.

Overall, about 23 percent of the participants were infected with a high-risk strain of genital HPV, the report found. These strains were slightly more common in men than in women. About 25 percent of the men were infected with a high-risk strain of genital HPV, compared with 20 percent of women. 


Typically Harmless Virus May Trigger Celiac Disease

A usually harmless virus may play a role in triggering celiac disease, a new study in mice suggests.

The researchers found that, among mice that were genetically engineered predisposed to celiac disease, those that were infected with a virus called reovirus were more likely to have an immune response against gluten than mice not infected with a reovirus. This immune response is similar to what's seen in people with the condition.

Although human infections with reoviruses are common, the viruses don't cause symptoms in people. But the study also found that patients with celiac disease did have higher levels of antibodies against reovirus, compared to people without the condition.

The findings suggest that reovirus infection may leave a "permanent mark" on the immune system that sets the body up for developing celiac disease, the researchers said.

"A virus that is not clinically symptomatic can still do bad things to the immune system and set the stage for an autoimmune disorder," such as celiac disease, study co-author Dr. Bana Jabri, director of research at the University of Chicago Celiac Disease Center, said in a statement.

The researchers also found people with celiac disease who had high levels of reovirus antibodies also had increased expression of a gene that encodes a protein called IRF1. In the mouse studies, the researchers saw that IRF1 played a role in developing gluten intolerance after reovirus infection.


Close to Half of American Adults Infected With HPV, Survey Finds

More than 42 percent of Americans between the ages of 18 and 59 are infected with genital human papillomavirus, according to the first survey to look at the prevalence of the virus in the adult population.

The report, published on Thursday by the National Center for Health Statistics, found that certain high-risk strains of the virus infected 25.1 percent of men and 20.4 percent of women. These strains account for approximately 31,000 cases of cancer each year, other studies have shown.


Wednesday, April 5, 2017

The Normalization Fallacy: why much of "critical care" may be neither

If our ancestors 100,000 years ago were getting infected with some organism and that infection was making their potassium low and they were dying as a result, would you not expect some sort of mutation in the aldosterone receptor that is activated during sepsis or some other compensatory mechanism? Did evolution fail? Must she lean on the diligent medical student with a K-rider to cover her shortcomings? Is that the most likely explanation, or is the most likely explanation that low potassium during sepsis is an epiphenomenon of all the compensatory cascades, resulting from millions of years of evolution, that protect us from the ravages of infection? Worse, could low potassium during sepsis be adaptive, and we are harming patients when we "replace" it? (Note that "replacement" implies that something is missing – even the way we talk about these things belies our enculturated biases.)

The same logic could apply for almost every perturbation we see in laboratory values and physiological parameters in sepsis and critical illness: anemia, electrolyte derangements, body temperature changes, tachycardia, hypo- and hyper-tension, tachypnea, delirium, leukocytosis, elevated biomarkers such as troponin and BNP, lactate (watch the linked video you will be glad you did), d-dimers, coagulopathies, cortisol levels, anorexia during infection or stress – you name it. The sicker a patient gets, the more values go out of whack and the greater are the deviations from normalcy. 


Vitamin C, cure for most common cause of death in hospitals?

Paul Marik, MD, FCCP, FCCM
Chief, Division of Pulmonary and Critical Care Medicine
Eastern Virgina Medical School

It's hard not to get excited about news of a potentially effective treatment for sepsis, a condition that leads to multiple organ failure and kills more people in the hospital than any other disease.

But there have been so many false promises about this condition over the years, it's also wise to treat announcements — like one published online by the journal, Chest — with caution.

The study, from Eastern Virginia Medical School in Norfolk, Va., reported some remarkable success in treating patients who were at high risk of sudden death.

The story began in January, 2016, when Dr. Paul Marik was running the intensive care unit at Sentara Norfolk General Hospital. A 48-year-old woman came in with a severe case of sepsis — inflammation frequently triggered by an overwhelming infection.

"Her kidneys weren't working. Her lungs weren't working. She was going to die," Marik said. "In a situation like this, you start thinking out of the box."

Marik had recently read a study by researchers at Virginia Commonwealth University in Richmond. Dr. Berry Fowler and his colleagues had shown some moderate success in treating people who had sepsis with intravenous vitamin C.

Marik decided to give it a try. He added in a low dose of corticosteroids, which are sometimes used to treat sepsis, along with a bit of another vitamin, thiamine. His desperately ill patient got an infusion of this mixture.

"I was expecting the next morning when I came to work she would be dead," Marik said."But when I walked in the next morning, I got the shock of my life."

The patient was well on the road to recovery.

Marik tried this treatment with the next two sepsis patients he encountered, and was similarly surprised. So he started treating his sepsis patients regularly with the vitamin and steroid infusion.

After he'd treated 50 patients, he decided to write up his results. As he described it in Chest, only four of those 47 patients died in the hospital — and all the deaths were from their underlying diseases, not from sepsis. For comparison, he looked back at 47 patients the hospital had treated before he tried the vitamin C infusion and found that 19 had died in the hospital.


Chest. 2016 Dec 6. pii: S0012-3692(16)62564-3. doi: 10.1016/j.chest.2016.11.036.
Hydrocortisone, Vitamin C and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study.
Marik PE1, Khangoora V2, Rivera R3, Hooper MH2, Catravas J4.

During the treatment period consecutive patients with a primary admitting diagnosis of severe sepsis or septic shock and a PCT > 2 ng/ml were treated with intravenous vitamin C (1.5 gm q 6 hourly for 4 days or until ICU discharge), hydrocortisone (50 mg q 6 hourly for 7 days or until ICU discharge followed by a taper over 3 days) as well as intravenous thiamine (200 mg q 12 hourly for 4 days or until ICU discharge).


In this observational study the combination of intravenous vitamin C, moderate dose hydrocortisone and thiamine appeared to have a marked effect on the natural history of patients with severe sepsis and septic shock. No patient in the treatment group developed progressive organ failure and the four deaths in this group were related to the patients underlying disease; these patients did not die from sepsis related complications. Our study evaluated the use of intravenous vitamin C, hydrocortisone and thiamine in a real world setting where all eligible patients with sepsis were studied. This is important as less than 20% of eligible patient with severe sepsis and septic shock are commonly included in many of the sepsis trials limiting the applicability and generalizability of the results.61 Furthermore, we did not test an expensive, proprietary designer molecule, but rather the combination of three cheap and readily available agents with a long safety record in clinical use since 1949. 62;63

Experimental studies performed over the last 20 years have demonstrated that both vitamin C and hydrocortisone have multiple and overlapping beneficial pathophysiologic effects in sepsis. Vitamin C is a potent antioxidant which directly scavenges oxygen free radicals, restores other cellular antioxidants including tetrahydrobiopterin and α-tocopherol and is an essential co-factor for iron and copper containing enzymes. 70;71 Both drugs inhibit nuclear factor Ƙ-B (NF-ƘB) activation down regulating the production of proinflammatory mediators, increase tight junctions between endothelial and epithelial cells, preserve endothelial function and microcirculatory flow, and are required for the synthesis of catecholamines and increase vasopressor sensitivity.13-15;26;70-75 Vitamin C plays a major role in preserving endothelial function and microcirculatory flow.70;72 In addition, vitamin C activates the nuclear factor erythroid 2-like 2 (Nrf2)/ heme oxygenase (HO)-1 pathway which plays a critical role in anti-oxidant defences and enhances T cell and macrophage function. 76-78


While the dosing strategy for corticosteroids (hydrocortisone) in patients with severe sepsis and septic shock has been well studied,26;88 that for vitamin C is more uncertain. Critically ill patients have either very low or undetectable vitamin C levels (normal serum levels 40-60 umol/l).18;19 Due to the saturable intestinal transporter (sodium-vitamin C transporter-1), 20;83 oral administration of doses as high as 1500 mg cannot restore normal serum levels. 20 To achieve normal serum vitamin C levels in critically ill patients, a daily dose of more than 3 gm is required. 16;18;21

Due to the lack of clinical equipoise and the ethics of withholding a potentially lifesaving intervention, we were unable to initiate a RCT in our center.


Monday, April 3, 2017

BPA and 'BPA-free' alternative linked to fetal brain changes - LA Times

The latest study was conducted on larval zebra fish, an animal whose brain development proceeds similarly to that of human fetuses. Newly hatched zebra fish exposed to very low levels of the neuroendocrine-disrupting chemical BPA displayed bursts in activity -- an anxiety-like behavior -- that were nearly threefold the level seen in normally developing zebra fish larvae.

While low-level exposure to BPA prompted a 180% increase in the production of neurons in the hypothalamus of zebrafish, exposure to BPS boosted neurogenesis during a key window by 240%.

The new research and nearly a dozen studies of BPA's physiological and behavioral effects in humans "begin to point to the prenatal period as a period of BPA vulnerability" and "suggest that pregnant mothers limit exposure to plastics and receipts" -- two classes of products in which BPA continues to be widely used.

It may be most important to avoid exposure to such industrial chemicals in the second trimester of pregnancy, a formative period for the brain in which neurons are born, specialized brain regions emerge, and synapses begin to lash together the resulting community of cells. Hormones play key roles in all of those processes, and the signals they provide often dictate the duration and sequence of neuronal development.

The study, published online Monday in the journal Proceedings of the National Academy of Sciences, also calls into serious question the safety of the chemical most widely used in products labeled "BPA-free," and therefore marketed as a safer alternative to BPA. A recent analysis of Americans' and Asians' urine samples confirmed previous work in finding that, while 93% had detectable levels of BPA, 81% had detectable levels of BPS.


Bisphenol-A (BPA) Disrupts the Hypothalamic Feeding Circuitry

Bisphenol-A (BPA) is a component of polycarbonate and other plastics to which humans are regularly exposed at low levels. BPA is characterized as an endocrine disruptor due to observations of its estrogenic activity in various experimental models. We have previously shown evidence of disrupted hypothalamic feeding circuitry and leptin sensitivity in adult BPA-exposed animals subject to a high-fat diet, but because these animals were already exhibiting a diet-induced obese phenotype, we could not rule out the possibility that these observations were simply consequences of the obesity, not a pre-existing phenotype produced by BPA exposure. Here we study leptin sensitivity and hypothalamic structure in young BPA-exposed animals prior to the onset of a body weight or metabolic phenotype. Pregnant and lactating CD-1 mice were exposed to either BPA or diethylstilbestrol (DES) at low, environmentally relevant doses via their diet. Studies of leptin function and neurobiology were conducted on offspring at a number of timepoints. Young adult offspring from this experiment were resistant to leptin-induced suppression of food intake, body weight loss, and hypothalamic POMC upregulation. Both male and female BPA-exposed mice showed a reduced density of Pro-Opiomelanocortin (POMC) projections into the paraventricular hypothalamus (PVN). BPA-and DES-exposed pups had respectively delayed and blunted postnatal leptin surges, and POMC projections into the PVN were rescued in female BPA-exposed animals given daily injections of supplemental leptin. Our findings suggest that BPA, a putative obesogen, may exert its effects through developmental programming of the hypothalamic melanocortin circuitry, permanently altering the neurobiology of metabolic homeostasis.


Sunday, April 2, 2017

Why Cereal Has Such Aggressive Marketing

Breakfast is often lauded as “the most important meal of the day.”

What is less commonly mentioned is the origin of this ode to breakfast: a 1944 marketing campaign launched by General Foods, the manufacturer of Grape Nuts, to sell more cereal.

During the campaign, which marketers named “Eat a Good Breakfast—Do a Better Job,” grocery stores handed out pamphlets that promoted the importance of breakfast while radio advertisements announced that “Nutrition experts say breakfast is the most important meal of the day.”

Ads like these were key to the rise of cereal, a product launched by men like John Harvey Kellogg, a deeply religious doctor who believed that cereal would both improve Americans’ health and keep them from masturbating and desiring sex. (Only half of his message made it into the ads.)

Before cereal, in mid-1800s America, breakfast was not all that different from other meals. Middle- and upper-class Americans ate eggs, pastries, and pancakes, but also oysters, boiled chickens, and beefsteaks. The rise of cereal established breakfast as a meal with distinct foods and created the model of processed, ready-to-eat breakfast that still largely reigns. And it all depended on advertising that suggests that breakfast is the most important meal of the day.

Before the  invention of cereal, breakfast was not as standard or routine as it is now. "The Romans believed it was healthier to eat only one meal a day," food historian Caroline Yeldham has said. Many Native Americans, Abigail Carroll writes in The Invention of the American Meal, ate bits of food throughout the day (rather than at set meals) and sometimes fasted for days at a time.

Of medieval Europe, historians alternatingly write that breakfast was only a luxury for the rich, only a necessity for laborers, or mostly skipped. And while many American colonists ate breakfast, it was a reputedly harried affair that took place after hours of morning work.

Historians tend to agree that breakfast became a daily, first-thing-in-the-morning institution once workers moved to cities and had set schedules. In Europe, this first began in the 1600s, and breakfast achieved near ubiquity during the Industrial Revolution. With people going off to a full day’s work, breakfast became a thing. By this time, there was already a tradition of certain foods—like bread, ale, cheese, porridges, or leftovers—being cooked or eaten in the morning. Although, since chroniclers of history spend little time describing breakfast, tracing the origins of favorite dishes is difficult.

Why are eggs a staple of brunch? Searching for the eggs–breakfast link takes one back at least to early history; John A. Rice, a Bible scholar, describes Mary of Nazareth preparing eggs for a breakfast attended by Jesus. What about pancakes? Paleontologists speculate that humans ate primitive pancakes over 5,000 years ago; more recently, Thomas Jefferson enjoyed crepe-like flapjacks.

But once breakfast became an American institution, the meal grew increasingly like dinner. “Americans wanted meat, meat, meat. And potatoes. And cake and pie,” Lowell Dyson, an agricultural historian, wrote of food preferences in 19th-century America. This mania extended to breakfast, and dishes like beefsteaks and roasted chickens joined staples like cornbread, flapjacks, and butter on American breakfast tables.

It was not a recipe for good health. Americans complained chronically of indigestion, which early nutritionists and reformers named dyspepsia. As the historian Abigail Carroll has explained, “Magazines and newspapers [just overflowed] with rhetoric about this dyspeptic condition and what to do about it.” It was the 1800s equivalent of today’s conversations about obesity.

Americans needed a simpler, lighter breakfast. What they got was cereal.

Before cereal represented an over-sugared, overprocessed relationship with food, Americans viewed cereal as a health food. Its origins lie in sanitariums run in the mid- to late 1800s. It was a period when doctors were still often called quacks: Germ theory was just gaining prominence, and Dr. John Harvey Kellogg’s favorite medical tool was a bath. His malady cures resembled spa treatments; “hydrotherapy” was popular at the time.

Kellogg and his peers believed they could improve Americans’ health by changing their diets. They thought that too much meat and too many spices had negative effects, and they preferred whole grains to white breads. A dietary reformer named Sylvester Graham invented the graham cracker in 1827. James Caleb Jackson, who did not allow red meat at his sanitarium, invented a cereal that he named “granula” in 1863. And Kellogg developed corn flakes in the 1890s.

The original versions of these cereals were spartan affairs. They were not sweet, and people had to soak Jackson’s granula in milk just to make it edible. Critics called granula “wheat rocks.”

But people wanted them. "The first year that the product was available saw more than 50 tons manufactured and sold in spite of primitive production facilities,” a Kellogg biographer wrote of his corn flakes. “Soon cereal manufacturing companies sprang up all over the country.” By 1903, there were 100 cereal companies in Kellogg’s town of Battle Creek alone.

It was a full-on craze. Cereal was seen as a solution to the nation’s dyspepsia, the author Abigail Carroll argues, and since it didn’t need to be cooked, it was a convenience food at a time when, post-Industrial Revolution, people had stricter schedules and less access to a kitchen or farm.

The most successful food trends tend to combine science and morality, and the invention of cereal was no exception. Kellogg termed his lifestyle—more exercise, more baths, and simpler, blander foods—”biologic living,” and he gave lectures and wrote long tracts to promote it. He described the modern diet as unnatural and too diverse. “To eat biologically,” he wrote, “is simply to eat scientifically, to eat normally.” Like a paleo devotee, he promised a return to man’s “natural” diet.

But Dr. Kellogg believed that eating biologically would solve much more than dyspepsia and indigestion. Like Dr. Graham with his graham cracker, Kellogg believed Americans’ meat-centric diets led them to carnal sins. "Highly seasoned [meats], stimulating sauces... and dainty tidbits in endless variety,” wrote Kellogg, a vegetarian, “irritate [the] nerves and … react upon the sexual organs.”

In his mind, masturbation was a shameful act linked to bad health, and over-stimulating diets, diseases, and sexual acts formed an insidious cycle. Eating cereal would keep Americans from masturbating and desiring sex, he insisted. "How many mothers, while teaching their children the principles of virtue in the nursery,” he wrote, “unwittingly stimulate their passions at the dinner table until vice becomes a physical necessity!" (He also recommended circumcision and tying children’s hands with rope to prevent masturbation and sexual urges.)

Kellogg was a true believer. During his lectures, he explained how people could make their own cereal at home. "You may say I am destroying the health food business here by giving these recipes,” he said at one talk. “But I am not after the business; I am after the reform."

Like any food trend, though, the marketers took over the purists’ work. Kellogg felt particularly bitter about the development: The two most successful cereal entrepreneurs were his brother, Will Keith Kellogg, and one of his former patients, C.W. Post, who Dr. Kellogg accused of stealing the corn-flake recipe from his safe.

Each man created cereal companies, the Kellogg Company (which was headed by Will Kellogg and not Dr. Kellogg) and Postum Cereal Company (now Post Cereals). Both of them became wildly successful thanks to two key ingredients: sugar and advertising. By the 1940s, Post Cereals coated its cereals with sugar. The Kellogg brothers had long argued over adding it. Dr. Kellogg believed sugar was a vice in his pure creation, while Will Kellogg thought it was necessary to improve the taste of their “horse-food.” After some hand wringing, the Kellogg Company copied Post and coated corn flakes with sugar.

Still, cereal kept its health-food reputation, thanks in part to a constant barrage of advertising. Cereal manufacturers like C.W. Post claimed that cereal cured everything up to malaria and appendicitis. The proclamations on today’s cereal boxes that they are “a good source of Vitamin D” date back to Americans’ obsession with vitamins in the 1920s. To appeal to children, cereal companies pioneered the use of cartoon mascots. Characters like Tony the Tiger and Snap, Crackle, and Pop first appeared in the 1930s.

Advertising was they key to the cereal business. Whether they involved cartoon characters or wacky health claims, the important thing was to establish a brand for each cereal. “The sunshine that makes a business plant grow,” C.W. Post said, as he embarked on a career that would earn him a net worth (in 2016 dollars) of $800 million, “is advertizing.”

Cereal and breakfast foods don’t have a monopoly on animated mascots and zany health claims. But there are a number of reasons why the battle over breakfast is particularly ferocious.

The first is that any company that convinces people to eat their cereal, pop tarts, or bagels owns that person’s breakfast, because so many people eat the same breakfast every day.

Studies have found that consumers have strong brand loyalty to breakfast foods like cereal. Breakfast choices are likely more habitual because of the strength of morning routines. Ads by the chicken lobby may convince people to eat a bit more chicken, but an avalanche of Tony the Tiger ads can get tens of thousands of children to eat Frosted Flakes every morning for years.

Another is that while some Americans cook breakfast, people’s desire for a fast, convenient meal means that many breakfast foods are packaged products that rely on advertising. This can be gleaned from the structure of the cereal industry: Cereal is extremely easy to make—a fact that angered Dr. Kellogg, who patented his creation but failed to prevent others from copying it—yet just a few companies dominate the market.

As the Federal Trade Commission once complained in an antitrust lawsuit, competing with the cereal giants is difficult because they create dozens of cereal brands and promote “trademarks through intensive advertising [which] results in high barriers to entry into the cereal market.” The magic of Snap, Crackle, and Pop—and all the advertisements for cereals, pop tarts, yogurts, and breakfast bars—means high profits from an easily imitated product.

Another reason why the marketing battle over breakfast is so fierce is that corporations have for decades seen it as the meal that offers the most opportunity to wring out more food spending from consumers. Why have fast food chains focused more on advertising egg McMuffins, waffles from White Castle, and Taco Bell breakfast burritos? As those working in the industry explained to Time, “throughout the fast food world, lunch and dinner sales have been flat for years, while breakfast sales have climbed steadily.” The same logic is at play in cereal makers’ 1944 marketing strategy—the one that coined the phrase “Breakfast is the most important meal of the day.” “Breakfast is the grocer's most promising target,” one ad man explained. “Lunch and dinner in the average American home are fairly well set."

Did marketers and executives genuinely believe in the value of promoting cereal as a healthy breakfast? Nutritionists had debated back and forth for decades whether America’s increasingly desk-bound workforce needed a hearty breakfast. But by the time of the 1944 ad campaign, during World War II, government nutritionists had sided with the pro-breakfast camp. In the interest of improving the health of army recruits, they teamed up with cereal companies to suggest that everyone eat a “good breakfast of whole-grain cereal and fruit.”

Nutritionists are less certain about the value of this advice today. Those studying the issue say that studies supporting the importance of breakfast for weight management have been contradicted by more rigorous examinations—and that studies examining the importance of breakfast in children’s diets have failed to show that breakfast (by itself) helps them focus on their schoolwork. But marketers won’t be saying so anytime soon. Breakfast is the most skipped meal in America, which means money on the table for the food industry.

Be vigilant. Breakfast is the most marketed meal of the day.



A Role for N-Acetyl Cysteine in Treating Parkinson's Disease

People with Parkinson’s disease may benefit from supplementation with N-acetyl cysteine (NAC), a powerful antioxidant that may also enable damaged dopaminergic neurons to recover some function.

A new pilot study from Thomas Jefferson University showed that Parkinson’s patients who took NAC daily for three month showed significant improvements on clinical evaluations of mental and physical abilities, as well as beneficial changes on brain imaging studies that tracked levels of dopamine.

The study, recently published on PLOS ONE, suggests that NAC has direct effects on the dopamine system in Parkinson’s patients.

Consistent Protective Effect
Daniel Monti and colleagues at TJU studied a small cohort of 23 Parkinson’s patients, all of whom were living independently, and already on standard drug therapies, which they continued throughout the course of the three-month trial.

The patients were randomized into two groups, with the first group receiving a combination of oral NAC, 600mg twice daily, plus weekly intravenous infusions of NAC (50mg/kg). The second group received no NAC, but remained on standard Parkinson’s drug therapy. The researchers made comprehensive evaluations at baseline and again after three months, using standard clinical measures like the unified Parkinson’s Disease Rating Scale (UPDRS), and a DaTscan SPECT brain scan, to measure the amount of dopamine transporter in the basal ganglia.

The data showed that NAC exerted a consistent, protective effect.

Compared to the controls, the patients that received the oral/intravenous NAC had improvements of 4-9% in dopamine transporter binding in the caudate and putamen regions of the brain (p<0.05 for all values), and 13% improvements in their UPDRS scores (p= 0.01). The mean UPDRS score dropped from 25.6 to 22.3 in the NAC-treated group.

The authors note “a significant correlation between the change in UPDRS scores and the change in dopamine transporter binding in the caudate and putamen.” They also point out a significant change in midbrain serotonin transporter binding in the NAC group, though not in the control cohort.

Oxidative Stress in PD
There is a growing body of data suggesting that oxidative stress is an important factor in the pathophysiology of Parkinson’s. Brain tissue samples from people with the disease show evidence of increased in lipid peroxidation, protein oxidation, and DNA oxidation.

Monti and colleagues point out that, “reactive oxygen species (ROS) are derived from dopamine itself, which is chemically unstable and undergoes auto-oxidation to form dopamine quinones (DAQs) and superoxide anion radicals. The DAQs can further act as oxidants thus supporting ROS formation. Auto-oxidation of dopamine may be increased in the early stages of PD when dopamine turnover is increased to compensate for dying dopaminergic neurons.”

Further, Parkinson’s’ brains tend to show decreased levels of glutathione, arguably the body’s most important antioxidant. The degree of neuronal glutathione depletion tracks closely with the severity of disease symptoms, and is the earliest known indicator of nigral degeneration.

Dr. Monti’s current clinical study was based on earlier cell culture work showing that NAC can prevent oxidative damage and neuronal cell death in vitro. A series of rodent studies suggested that NAC could increase glutathione levels, neutralize hydrogen peroxide radicals as well as toxic dopamine-related quinones, and prevent neuronal death.

Acknowledging the limitations inherent in a non-blinded pilot trial involving a small number of patients, the authors none the less believe that “NAC might positively impact dopamine function and potentially, clinical symptoms.” They contend that this subject is worthy of a large, randomized, blinded study.

Addressing Oxidative Stress
Toxins are everywhere in our environments these days, and oxidative stress is widely prevalent. A high burden of toxins can directly damage cells down to the mitochondria. Oxidative stress can lower immunity, increasing the vulnerability to autoimmunity, cancer, preventing weight loss and blood sugar issues.

It is increasingly obvious that toxins and oxidative stress play a role in the etiology of most common chronic diseases including insulin resistance and diabetes, heart disease, and strokes. Gut inflammation, leading to leaky gut, only amplifies the problem.

With so much at stake, we as clinicians need to pay much more attention to oxidative stress and toxin burdens in the patients we serve. Fortunately, we have some good nutraceutical tools, in the form of glutathione and NAC.
Glutathione is found in every cell of the body but has its highest concentration in the liver. Glutathione helps to mop up heavy metals, free radicals, and just about anything that can damage cells. Glutathione also helps with DNA protection, mitochondrial and immune support, protects against heart disease, cancer, dementia and other chronic illnesses.

Most diseases involve a glutathione deficiency leading to DNA damage and unhealthy cells.

NAC is a precursor to glutathione, and supplementation can restore intracellular levels of glutathione. As this new study suggests, it may also help to reduce oxidative damage in the brain, by increasing neuronal glutathione.

 To optimize detoxification and improve our immune systems, we can help our bodies make glutathione simply by eating plenty of garlic, onions, cilantro, and cruciferous veggies like broccoli, kale, cauliflower and cabbage.

For those with a high toxic load, and—as the Monti paper suggests, for those at risk of Parkinson’s’—NAC supplementation makes good sense.

The world around us can be a scary place. It seems our bodies are being bombarded in all directions with pesticides, heavy metals, pharmaceutical metabolites, estrogen-mimicking compounds, radiation, and other toxins.

All the research on glutathione and NAC suggest that these supplements can optimize our detoxification capacities, reducing the overall negative effects of oxidative stress, and improving our resilience.

Rather than putting up fences, let’s protect ourselves from a toxic environment with love, friendships, and “superhero” antioxidants like glutathione and NAC!

Madiha Saeed, MD