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Long-Haul Lyme Disease

This is an update to a story I wrote five years ago, for Johns Hopkins Rheumatology’s LEAP Magazine, with two world experts on PTLD: post-treatment Lyme disease.  They have uncovered some promising clues as to why, for some people, Lyme disease doesn’t go away, and identified some new potential avenues of treatment.

Some people get bitten by a deer tick that’s infected with Borrelia burgdorferi, develop a rash, are diagnosed with Lyme disease, take antibiotics, feel better, and get their life back to normal.

Others aren’t so lucky.  Diagnosed just as promptly, they take the exact same course of antibiotics.  And then…  they don’t get better.  What’s happening?

John Aucott, M.D., an infectious diseases specialist and the founding Director/physician of the Johns Hopkins Lyme Disease Research Center, is a world authority on this “post-treatment Lyme disease” (PTLD), a condition he helped define.  Its symptoms are persistent, and can include fatigue, pain, weakness, brain fog, and sleep disorders. He has studied and treated hundreds of patients with PTLD, who tell him things like, “I can’t get out of bed,” or “I can’t ride my bike,” or “I’m exhausted trying to get through the work day.”  In addition to feeling ill, frustrated, discouraged and even desperate for relief, these patients often must deal with a stigma – similar to that experienced by a brand-new group of patients from the pandemic, the Covid-19 ‘long-haulers,’ Aucott says.  “The Covid long-haulers aren’t dying, they don’t have signs of extensive organ damage – but they have the exact same lingering, disabling symptoms that we have been pointing out for years in our PTLD patients.”

Aucott and his longtime colleague, scientist Mark Soloski, Ph.D., suspect that for the PTLD “long-haulers” – about 10 to 15 percent of people treated for acute (initial) Lyme disease – the disease process triggers persistent changes in the immune system and the autonomic nervous system.  Their pioneering research program focuses on defining and characterizing changes in the underlying molecular mechanisms that cause and perpetuate these symptoms, with the hope of finding biomarkers to help diagnose and monitor this disease, and to discover new avenues of treatment.  Their areas of active study include:

The gut microbiome:  In work recently published online in mBio, Soloski, Aucott and colleagues at Hopkins, Northeastern University, and University of California-San Diego reported that PTLD patients have a distinct microbiome “signature,” or population of bacteria in their gastrointestinal tract compared to healthy controls and to an intensive care unit control group.  The scientists analyzed fecal samples from patients in the Hopkins Study of Lyme Immunology and Clinical Endpoints (SLICE), and compared them to a healthy control group and to an intensive care unit (ICU) control group – patients who were also on antibiotics.   “We found that the PTLD group had two distinct differences in their gut bacteria – an abundance of Blautia bacteria, and a decrease in Bacteroides,” says Soloski.  “Bacteroides is interesting, because it produces GABA, an important neurotransmitter.”  Low levels of GABA can cause anxiety and depression.  In turn, an excess of Blautia has been found in people with obesity, Alzheimer’s disease, and multiple sclerosis.  The good news about the gut microbiome is that it can be altered by many factors, including diet, medication, and even fecal transplant.  It may be that reintroducing healthy bacteria into the colon could significantly improve quality of life in these patients – a compelling idea that the investigators feel is worthy of further study.

 The metabolic response:  In another study, Soloski, Aucott and colleagues at Hopkins, the centers for Disease Control, Colorado State University, and New York Medical College found significant metabolic differences in people with PTLD compared to other patients.  This work was published in Clinical Infectious Diseases.   “Basically, we found that the metabolome – all those small molecules our cells make and pour out into our blood, our signature of the metabolic activities of all the cells in the body – is perturbed in patients with Lyme disease.”  The scientists have identified a “fingerprint” of metabolites unique to patients with PTLD.  This might one day lead to a blood test to determine which patients with Lyme disease are at risk of PTLD, and to help monitor the course of illness in PTLD patients.

Is there a genetic fingerprint?  Soloski and Aucott are looking for epigenetic changes – small mutations in the structure of DNA – among the 20,000 or so genes in the genome.  This is big-data analysis that wouldn’t have been possible a few years ago.  Computers and data experts sift countless pieces of evidence, like miners sluicing for gold, looking for valuable nuggets:  patterns of gene expression, particularly in immune system genes and in messenger RNA genes.

 

Not Always a Bullseye

Artificial intelligence (AI) is making possible what John Aucott describes as his “pet project:” analyzing the rash that comes at the start of Lyme disease and is key to early diagnosis.  “Our studies show that many people have trouble making the right diagnosis.  Everybody’s looking for the Target store sign,” but that distinctive bullseye only appears in 20 percent of patients.  “Patients and clinicians miss the other 80 percent.  We trained the computer by AI to read cell phone images and make a better diagnosis.”  Aucott was senior author on a report of this work, recently published in Computers in Biology and Medicine.

Could rashes even help predict which patients might be headed for PTLD, and could a better understanding of rashes lead to more effective, personalized treatments?  These are possibilities Aucott hopes to explore.

 

Better treatment for PTLD

            “There is no FDA-approved treatment for PTLD,” says Aucott, “so we use drugs that the FDA has approved for other indications.  Treatment is very patient-specific, depending on the primary symptoms.”  For example, fatigue often goes along with postural orthostatic tachycardia syndrome (POTS), a condition where the heartbeat skyrockets with a change of position – from sitting to standing, for example – that is treated by blood pressure-regulating drugs such as midodrine.

            In exciting research recently published online in BMJ Open, Hopkins scientists Alison Rebman, Ting Yang, and Aucott, have identified six symptom factors and three potentially clinically relevant subgroups among patients with PTLD.  The group’s findings may be an important step toward developing even more personalized and specific treatment plans. 

Aucott has spent years working to raise physician awareness about PTLD, which “doesn’t fit into one specific disease silo” or subspecialty; in fact, the Center is the only one of its kind based in an academic department of medicine in the world with a focus on PTLD.

New to the Center is rheumatologist John Miller, M.D., who brings expertise in joint ultrasound.  “He is showing changes in our patients that are subtle,” particularly “tendinopathy-related causes of periarticular pain that nobody’s seen before, because joint ultrasound has never been done in these patients.”  Miller has found enthesitis, inflammation where tendons insert into the joints that is also found in psoriatic arthritis and Reiter’s syndrome (reactive arthritis).  His findings “may lead to looking at autoimmune-related drugs,” says Aucott, and the images “are opening up a whole new field of clinical inquiry.  Nobody else is really doing this.”

You can learn more about the Center here.

©Janet Farrar Worthington

 

 

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How Inflammation Sparks Prostate Cancer

Believe it or not, there once was a time when the Grand Canyon was just a ditch.  Before that, it was a rough patch in the desert with a river running through it.  It took a very long time for that canyon to form, and the conditions had to be just right to allow water, blazing sun and wind to chip away through layers of fragile rock.

On a very much smaller scale, this is what happens to cause cancer when the conditions are just right.

Now, if you will:  While we’re thinking about the Grand Canyon, let’s pan the camera a few miles away. We’re near some tall pine trees, and there’s a campfire.  Some cowboys are sitting around it.  Let’s imagine that they all have white hats; they’re good guys.  (They’re also much quieter than the cowboys around the campfire in “Blazing Saddles,” so don’t go there!)

If you’ve ever sat around a fire, you know that wood sometimes pops unexpectedly and sends out sparks.  That’s exactly what happens at our little campfire, and it happens to hit one of the cowboys square on the arm.  He brushes out the sparks, then goes back to his seat.  Nothing’s really changed; he laughs it off.

Wouldn’t you know it, the fire sparks up again – right on that same poor guy.  This time, he’s a little more scorched; his shirt has a hole in it and his eyebrows got singed.  He’s also a little irritated.

It happens a few more times, and he is no longer the proverbial happy camper.  He’s moving around, no longer sitting quietly, he’s got some burns that will leave scars, and he’s angry.  His hat is so charred now that it’s almost black.  One last spark, and he’s out of there.  He leaves the campfire, saddles up his horse, and rides away, fighting mad and looking for trouble.

This little scene plays out a lot, every day, in our bodies.  There are countless campfires – like stars dotting the sky – that flare up, burn quietly, get snuffed out, and never cause harm.  The campfires are little flares of inflammation.  

Commenting on this analogy is medical oncologist and molecular biologist Jonathan Simons, M.D., CEO of the Prostate Cancer Foundation.  “The future of fighting prostate cancer,” he says, “is either to stop the sparks from flying, or to put fire retardant on the flames – or better yet, to bring in the fire retardant really early in life.  It’s all about the sparks, and what makes the sparks, and then spark interception or spark interdiction.”

Expect to Hear a Lot More About Inflammation

Inflammation is our own version of Dr. Jekyll and Mr. Hyde: When it works the way it’s supposed to – when you skin your knee or get a paper cut on your finger, for instance – inflammation is what protects your body from bacteria and germs that find their way through the open wound.  The immune system kicks in; zealous home soldiers like killer T cells spray chemicals on the intruders, puncture their armor, or even eat them whole.  You notice some redness, a little heat, maybe some swelling or even a bruise, and you know that your body is healing.  There’s a scab, new skin covering the hole or tear, and all is well. The inflammation goes away.

But what if it doesn’t go away?   Here’s where the dark side of Dr. Jekyll, his alter ego Mr. Hyde, starts to show itself.  Chronic inflammation is bad.  

“The story of inflammation is absolutely the heart of what causes prostate cancer,” says Simons.  “Inflammation lowers your defenses,” and changes the DNA.  Going back to the angry cowboy at our campfire scene: If only he had moved away from the fire, or if someone had poured a little water on the fire to cool it down and keep the flames low.  He might have had a few scars, but he would have been okay.  Instead, he began moving around, and eventually he left the campsite; if he were a prostate cell, he would have become cancerous – but still there at the site, still easily treatable.   But as he became more scorched, he became metastatic.  The continued exposure to those flames turned him from a cell sitting quietly into a metastatic cancer cell.

“We estimate that 30 percent of all cancers are caused by this kind of chemistry,” Simons adds.  The little fires hurt genes that are nature’s own tiny fire retardants, so without their subduing effect the flames burn hotter; the fires then go after the body’s normal first responders.  So the firefighters don’t stop the burning; the paramedics don’t heal the injured victims.  The inflammation draws other cells called macrophages and granulocytes to the scene; they’re supposed to be part of the body’s cleanup crew.  “Unfortunately, in cleaning up, they actually make the flames burn hotter and further damage the area.”

What causes the fires? 

One huge cause is our diet.  Fat, charred meat, processed carbohydrates, chemicals in junk food, and sugar.  Basically, what we know as the Western diet – high in meat and bad carbs, low in fruits and vegetables.   How do we know this?  Because the men in the entire world least likely to get prostate cancer are men in rural Asia, who eat the traditional Eastern diet – low in meat, high in fruits and vegetables, with hardly any processed carbs.  No soda, lots of green tea.  No fries, lots of rice.  No burgers, lots of broccoli.  But when those men come to America, their risk of getting prostate cancer goes up.  Diet matters. 

“The rural Asian diet is anti-inflammatory,” says Simons.  “It may be that these men would eventually develop prostate cancer if they lived to be 120.  But they don’t.”  If you think about our campfire analogy, maybe cells still get singed, but they’re few and far between.  That critical momentum never develops.

“We are now learning that it’s essential for men to have a healthy diet when they’re young – say, between 14 and 30.”  But men of any age can benefit from turning down the inflammation with “fire-fighting” foods.

The opposite is also true:  Obesity and one of its consequences, diabetes, make these flames burn even higher.   (In fact, this may be one reason why rural Asian men are less likely to get prostate cancer: because of their diet, they have a lower body mass index, which means less stress on their cells.) “If you are overweight or borderline diabetic, you turn on more insulin to try to control your blood sugar,” says Simons.  Insulin secretes molecules called cytokines, which – thinking of our cowboys at the campfire – are like the chuck wagon, bringing in oxygen, new blood vessels and nutrients to feed the cancer.

“Some men have more sparks flying around, and men who are overweight are in this group.  The good news is that you can reduce your insulin level with exercise,” says Simons.  “There’s a lot of evidence that just being sedentary is a terrible setup for trouble later, if you have a slightly inflamed prostate and higher insulin level.”

The prostate is particularly vulnerable to inflammation, Simons adds, because it’s just chock full of inflammatory cells called prostaglandins, most likely nature’s way of protecting the fluid that makes up semen.  So the prostate is already a tinder box.

What else makes it worse?  A big one is genetics.  Some men are born with  their own fire-starter – genes they inherited from their father or mother.  If you are of African descent, or if you have a family history of prostate cancer or cancer in general, you are at higher risk of developing prostate cancer.  That doesn’t mean that you’re bound to get it, and it may be that with cancer-fighting diet, exercise, not smoking, and plain old good luck that you will never have prostate cancer.

Other causes of sparks:  Infection.   Cigarette smoking.  Emotional stress.  Not being circumcised: several stories have shown that circumcision has a protective effect, lowering your odds of developing prostate cancer, and of dying from it.  This ties in with what we’re still just learning about the role infection plays in changing the prostate’s microenvironment, and making it more susceptible to cancer.

            Okay, then what puts out the fires?

We’re still figuring this out.  A good diet, exercise, and other flame retardants such as Vitamin D.  Dietary supplements such as turmeric seem to help, as do broccoli and tomatoes cooked in olive oil (which brings out the lycopenes).  Meditation: new research suggests that this may help calm the tiny sparks and lower the chances of cancer catching fire.

And finally, there’s a huge question mark. What else helps?  “This area of research is woefully underfunded,” says Simons. There may be a bacterial equivalent of H.pylori– the nasty bacteria found to cause stomach ulcers.   New research suggests that probiotics – “good” bacteria that change the microflora in the gut – may prove helpful in preventing cancer.  Does this mean that there are bad bacteria that do their share of causing it?  Could this be related to the link between infection and inflammation?

We don’t know.  Stay tuned.

 

In addition to the book, I have written about this story and much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

 

 

 

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Cancer, Gut Bacteria, and Your Poop

What does your poop reveal about your gut bacteria (called the gut “microbiome”), and what does this have to do with your immune system’s ability to fight off cancer? Just how important is this gut flora, or bacteria, anyway?

Let’s look at the last question first. How important is your gut bacteria? It’s very important to your whole body: your brain, your heart, your immune system – and, although no one has proven it yet, we suspect that it is also very important to your prostate. Being able to empower the gut bacteria – to increase certain “good” bacteria that, in turn, will help the immune system do a better job of fighting off disease – may soon help people with some types of cancer respond better to immunotherapy.

Recently, scientists studying colon cancer found that certain bacteria are found in half of all colon tumors and when the cancer spreads, the bacteria spread right along with them. In another study, scientists found that two different forms of bacteria work together, like fertilizer, to help colon cancers grow. In still other work, scientists studying melanoma found that the presence of certain gut bacteria can change how cancer patients respond to immunotherapy.

I have written about understanding and tapping the power of the gut bacteria here, and here, as it relates to irritable bowel and depression. But cancer! This article mainly applies to prostate cancer, but the implications are rich for many types of cancer.

Could treating the bacteria help prevent cancer, make it less likely to spread, or make immunotherapy more effective against it? I recently interviewed Johns Hopkins scientist Karen Sfanos, Ph.D., whose work is shedding light on the role bacteria play in cancer – particularly, in prostate cancer – for the Prostate Cancer Foundation (PCF), which has invested $1 million in research to help explain the gut microbiome’s role in metastatic prostate cancer.  Call it a “gut feeling.”

Eight Pounds of Your Body Is Just Bacteria

Here’s something to consider about the megapopulation of bacteria in your gut: A lot of us have been exposed to bad bacteria, but these bugs don’t kill us. In our large intestine, we have about eight pounds or so of trillions of bacteria; in fact, we have more bacteria than cells in our bodies. Some of them are good, and some of them are not so good.

But some people die from bacterial infections in the gut; what happens to make them more susceptible? Dysbiosis: an imbalance, where the bad bacteria take over. For example: say you have an upper respiratory infection, and you get antibiotics. Antibiotics wipe out bacteria. They don’t distinguish between good and bad species; they just kill ‘em all. The good bacteria are collateral damage, and sometimes this scorched-earth result creates an opportunity for very bad bacteria to thrive in your gut. What’s going to fix that, more antibiotics? Maybe, but not always. In fact, when you wipe out the gut flora with antibiotics, an even worse form of bacteria – something nasty like C. difficile, for instance – can take over.

Again, what does this have to do with cancer? Here we go: If antibiotics fail, the most effective way to cure intractable C.difficile is with a fecal transplant: basically, taking the poop of someone who does not have C. difficile, who has a healthy gut microbiome, and inserting it in your colon. It’s gross, but it can also save someone from chronic, miserable illness.

Karen Sfanos is one of a few pioneering cancer researchers wondering if the same principle could apply to treating prostate cancer.   With colleagues at Hopkins and Thomas Jefferson, she is looking at gut bacteria – a heck of a lot of it, in at least a thousand patients undergoing various treatments for advanced prostate cancer. As principal investigator of the PCF grant, Sfanos is stockpiling gut bacteria and building a microbiome specimen repository that will serve as an international database for research.

Sfanos, a molecular microbiologist, has long been interested in the relationship between bacteria and prostate cancer; in fact, she is among a growing number of scientists who are proving that urine is not (as scientists supposed for decades) sterile, and was the first to describe the urinary microbiome in men with and without prostate cancer. Bacteria in the urinary microbiome may shed light on the presence of microbes that can cause prostate infections, including some that are sexually transmitted infections. These microbes may produce no symptoms but may lead to chronic inflammation – and this, in turn, may cause prostate cancer in some men.

Meanwhile, a few studies looking at other forms of cancer “started to indicate that the gut microbiome could have an influence on treatment response,” Sfanos says, “and that really got us thinking about whether the gut microbiome could influence how well men respond to prostate cancer treatment.”

In studies with medical oncologist Julie Graff, M.D., of Oregon Health & Science University, Sfanos has been working to see if there is a difference in the gut microbiome of men with widely metastatic prostate cancer who have responded dramatically well to the checkpoint-inhibiting immunotherapy drug, pembrolizumab.

Originally, Graff and colleagues suspected that the men in their studies who were exceptional responders to this drug had cancers with “microsatellite instability” (they had tumors with many genetic mutations) – which made the cancer cells stand out and be more easily recognizable as enemies to the immune system. And this is undoubtedly true, but it’s not the whole story.

In Graff’s initial small study, published in Oncotarget, three men out of 10 had dramatic responses: their metastatic tumors in the liver, brain, and elsewhere disappeared, and their PSA levels plunged. Tumor tissue from two of these men was available for further analysis and, indeed, one of the men’s tumors had microsatellite instability. But the other man’s tumor did not. The number of tumor mutations, explains Sfanos, “cannot fully explain those responses to immunotherapy,” in Graff’s and other studies. “People who do not have that phenotype are still having dramatic responses.”

For these men, “the gut microbiome could be contributing in several ways. If the immune system is blocked from recognizing the tumors,” because the cancer uses sneaky tricks and devious disguises to hide itself from the body’s roving immune system soldiers that would kill it, “the right mix of bacteria could help stimulate the immune system – and combining that with the immune checkpoint inhibitor might drive a robust anti-tumor immune response. So that could explain what’s happening in patients who do have this high mutational burden.”

What about the other people with various forms of cancer who do have microsatellite instability – the weird-looking, multi-mutated tumors that the immune system can see and say, “Hey, that’s not supposed to be here!” Why do only some of them respond well to immunotherapy? The gut may be helping them, too.   Is it diet? Do these people just eat better, and thus have a healthier gut microbiome?

“Certainly, diet does have a profound influence on the composition of your gut flora,” says Sfanos. To understand more, it’s time to look at your poop – or rather, at the poop of men with advanced prostate cancer who are contributing to this repository – in a very high-tech way. With each fecal sample, Sfanos and colleagues extract all of the bacterial DNA and RNA. They’re generating “microbiome profiles” that include bacteria, viruses, fungi, and protozoa. Then, they are correlating the gut flora with the treatment the men are receiving – and hoping to find answers to so many questions.

“I am extremely interested in the interplay between bacteria and circulating hormones,” says Sfanos. Does ADT – androgen-deprivation therapy, which deprives prostate cancer of the androgens, or male hormones, that nourish it – change the makeup of bacteria in the gut? “It’s an underappreciated relationship: they influence each other. The gut bacteria influence the circulating androgen levels, and vice versa. They’re talking to each other.”

In one ongoing study, “we looked at the gut flora of men across the prostate cancer spectrum,” Sfanos notes – men without prostate cancer, men with localized prostate cancer, men with recurrent prostate cancer, and men with metastatic prostate cancer. “We were really interested in determining if there are differences based on what treatments the men were being given. Oral anti-androgens, including abiraterone and enzalutamide, “may directly interact with the gut flora. We found that these men in our study had measurable differences in the composition of their gut flora. Something specific is going on in the men taking oral anti-androgens.” In further analyses, Sfanos and colleagues found that in men taking these drugs, “there are bacteria capable of hormone biosynthesis in the gut: microbes able to synthesize and metabolize precursors that can be hormones. This could potentially influence treatment response.” In other words, some gut bacteria can synthesize androgens that “could maybe even continue to nourish the tumor. We are very actively studying this right now.”

The gut flora, she adds, are “absolutely linked” to some of the other health problems that can accompany ADT, particularly metabolic syndrome. “This is very understudied in men with prostate cancer.” (Sfanos’s most recent work is currently in press, to be published soon in Nature’s journal, Prostate Cancer and Prostatic Diseases. In the meantime, here’s a link to a related study she did.

What might this research lead to? How could it help men with advanced prostate cancer fight their disease? Here’s one example Sfanos can envision. “Let’s say we discover a species of bacteria that’s capable of metabolizing an androgen,” a nasty bug that could counteract the effects of abiraterone by whipping up its own homemade batch of male hormones. “If depriving men of androgens leads to an outgrowth of some bacteria that can make their own androgen, we could check for them in a patient’s stool sample and try to get rid of them.”

Boosting the immune system: The epithelial barrier, the thin lining of the intestinal wall, is a virtual Checkpoint Charlie for immune system activity. This is a gateway with “a massive amount of immune cells on one side, and bacteria on the other side,” Sfanos notes. “Several studies have shown that certain species of bacteria are overrepresented in the gastrointestinal tract of people who respond to immunotherapy.” One research group has focused on a group of bacteria called Ruminococcaceae, and another is studying a microbe called Akkermansia muciniphila. Either of these, or both, may turn out to be very important. “The idea is that if, for whatever reason, the presence of these microbes is essential to generate a response to immunotherapy, you would want to introduce these bacteria,” in a fecal transplant or perhaps in the form of a targeted prebiotic or probiotic.

There probably won’t turn out to be one “magic bullet” form of bacteria, which is why a fecal transplant might be helpful. It is an intriguing idea: taking the gut bacteria from someone who responds extremely well to immunotherapy, and transplanting that – in poop form – into the colon of someone whose gut bacteria is not as beefed up for cancer-fighting. Would this stimulate the immune system so that it would knock out the cancer? Could it turn flabby, couch potato bacteria into ripped, mighty, cancer-fighting bacteria? And could this beefed-up bacteria help put your cancer into remission?

It’s early days yet. But if the bacteria within our bodies can shape how our immune system functions, if it can help determine how we respond to cancer treatment – or even whether we get cancer at all – then understanding the very complicated interplay between gut bacteria and cancer could be a game-changer.

“Historically, many prostate cancer biobanks have not included fecal samples,” says Sfanos. This means that nobody has correlated the other markers for how prostate cancer develops or progresses – PSA, Gleason score, genetic mutations, or clinical outcomes – with what’s happening in the gut.

Thanks to Sfanos and colleagues, that’s not the case anymore. Stay tuned.

In addition to the book, I have written about this story and much more about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org. The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  As Patrick Walsh and I have said for years in our books, Knowledge is power: Saving your life may start with you going to the doctor, and knowing the right questions to ask. I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask for it.

 ©Janet Farrar Worthington

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Sugartown

In 1993, I actually wrote that sugar and carbs were fine. Want to be healthy? Eat more pasta and healthy grains, I wrote. Fats were the big evil. I was so wrong – but this was what the studies showed. This is what many doctors believed. Fat was our enemy. Fat was the reason we were becoming – not nearly so much as we are now, I might add – a nation of lard butts.

For decades, this was reflected in packaged “healthy” foods. Eat as many cookies as you want: yes, they’re chock full of carbs and junk calories, but no worries! They’re LOW FAT. This was the new food gospel, and we saw it proclaimed on our grocery store shelves – low-fat chips, ice cream, cakes. Guilt-free! Breakfast cereal – great! It’s got NO FAT! We saw the birth of olestra, which not only had no fat – it was indigestible! Side effects included gas, cramps, bloating, diarrhea, and, most appalling of all, “anal leakage.” Lays potato chips, Ruffles, and Doritos at the time that were “FAT FREE” and contained olestra had the word “WOW” in huge letters right there on the bag. I guess they meant the taste, but maybe they were referring to what happened when you ate it, as in: “Wow! I just pooped my brains out!”

In 1967, Nancy Sinatra had a hit song called “Sugartown.” She sang, “I got some troubles, but they won’t last. I’m gonna lay right down here in the grass, and pretty soon all my troubles will pass” (most likely, she did not mean “pass” in the olestra way) “ ‘Cause I’m in shoo-shoo-shoo, shoo-shoo-shoo, Sugar Town.” There were about five more “shoos” in that line, but you get the drift.

Sugartown was the place to be. We believed it because of review articles like one that appeared in the New England Journal of Medicine (NEJM) the same year as “Sugartown” – 1967. It discounted evidence that linked sucrose consumption to coronary heart disease. Doctors believed it. They told their patients. Their patients believed them.

It turns out that this particular study was secretly funded by the Sugar Research Foundation (SRF). Now we know, thanks to a bombshell article recently published by University of California-San Francisco scientists in the journal, PLoS Biology, that the SRF (now defunct) was completely evil. It manipulated the science.

It not only “discounted evidence linking sucrose consumption to blood lipid levels and hence coronary heart disease,” report the study’s authors, Cristin Kearns, Dorie Apollonio, and Stanton Glantz. It also “withheld information from the public” linking sugar to changes in the microbiome that can lead to bladder cancer.

But it’s not just the SRF, which later became the International Sugar Research Foundation (ISRF); it’s a bunch of sugar industry trade associations. And it wasn’t just back in the 1960s. All of these groups have “consistently denied that sucrose has any metabolic effects related to chronic disease beyond its caloric effects,” Kearns, Apollonio and Glantz state. In other words, the main side effect these groups are willing to acknowledge is that sugar makes you gain weight.

Let’s take a moment here for me to say that I love sugar. I do. I love cookies, and chocolate cake, and coconut custard pie, and Mexican Coke with real cane sugar instead of corn syrup.  But I really limit it.  I don’t like food Nazis, who tend to be snarky and condescending and who alienate people who really could benefit from what they’re trying to say by making snide statements like, “What’s next, a deep fried stick of butter?” (I actually read that this week in a nutrition magazine that means well, but its tone is so snotty that it’s off-putting.)

That’s not what I’m trying to do at all. What I’m writing about here is the disturbing idea that sugar has been linked to serious illnesses and that the sugar industry has suppressed this information. If we had known six decades ago, maybe a lot more people would be alive now, and maybe our country wouldn’t be struggling so hard with obesity, heart disease, and diabetes.

In case you’re wondering, Kearns, D.D.S., M.B.A., is an assistant professor at the University of California San Francisco (UCSF) School of Dentistry. Stanton Glantz, Ph.D., is Distinguished Professor of Tobacco Control in the Department of Medicine at UCSF. He’s seen this same kind of twisting and distorting of medical evidence a lot; the tobacco industry did it for years. Dorie Apollonio, Ph.D., is an associate professor in the Department of Clinical Pharmacy at UCSF. Together, these UCSF researchers make a formidable team.

Now, back to the 60 years of manipulating the science and hiding the harmful effects of too much sugar. As recently as 2016, the Sugar Association issued a press release blasting findings from a study published in Cancer Research. In that study, done in mice, scientists found that dietary sugar induces increased tumor growth and metastasis when compared to a non-sugar starch diet. But instead of saying, “Hey, you know, maybe you might want to consider not eating so much sugar – all things in moderation,” the Sugar Association doubled down, stating that “no credible link between ingested sugars and cancer has been established.” Nothing to see here, move along, move along. Look over there – doughnuts with sprinkles!

In this PLoS paper, the UCSF scientists lay out a trail of damning evidence. In that first project in the 1960s, one group of rats was given a diet of 75 percent fat but no sugar. A second group of rats ate a diet of less fat, just 15 percent, but 60 percent sucrose, and their little bodies metabolized all that sugar as a carbohydrate. The sugar-eating rats developed thiamine deficiency, which then led to heart failure. But in the rats that ate more complex carbohydrates and no sugar, the gut bacteria, or microbiome, changed and actually started synthesizing thiamine.

This study intrigued SRF scientists, who thought that maybe, if the microbiome could be adjusted, the gut could tolerate sugar better. This idea led to Project 259, in which scientists led by W.F.R. Pover at the University of Birmingham in the UK studied the effect of sugar in the gut between 1967 and 1971. Pover’s team showed, in rats and guinea pigs, that eating more sugar led to higher levels of triglycerides; in turn, this led to higher levels of beta-glucoronidase in urine – a finding that’s linked to bladder cancer – and in an internal document, scientists described this research as “one of the first demonstrations of a biological difference” between rats that eat a lot of sugar and rats that don’t.

Project 259 didn’t just link sugar consumption to cancer, but to hypertriglyceridemia, an elevated level of triclycerides (a type of fat) that raises the risk of heart disease, say the UCSF scientists, and these findings stayed hidden for decades until the UCSF scientists uncovered them. Also suppressed was evidence linking higher doses of sugar to other “renal disorders, urinary tract infections, and renal transplant rejection.” Eat sugar – reject your donor kidney!

Even worse, the sugar industry did what every good magician knows how to do: misdirect. In previous research, published in the Journal of the American Medical Association (JAMA), Glantz and Kearns, with colleague Laura Schmidt, examined SRF internal documents and historical reports and found that the SRF secretly funded studies, including one published in 1965 in the NEJM, “promoting fat as the dietary culprit in coronary heart disease.”

Imagine there’s a gunshot, and the killer quickly places the murder weapon in somebody else’s hands and starts shouting, “He did it! It’s that guy!” and then slinks away. That’s what the sugar industry did.

For six decades, we have blamed fat – and as a society, we now look more and more like the tubby earthlings on the big spaceship in the Pixar movie, “Wall-e.” We’re huge, and we’re unhealthy.

Sugartown is not so sweet.

©Janet Farrar Worthington

 

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So Simple, But Does the Paleo Diet Make You Feel Better?

Does the Paleo diet, basically, eating lean meats, nuts, fresh fruits and vegetables – foods our Stone Age, hunter-gatherer ancestors could have eaten – really make you feel better?

If it does, then why?  And how, exactly? 

What happens to the microbiome – the countless bacteria that live inside the gut – when you stop eating dairy, processed sugars and carbs?

paleo diet foodsThis is what doctors at the Amos Center for Food, Body & Mind at Johns Hopkins Bayview Medical Center want to know.  Some of their patients who have irritable bowel syndrome (characterized by constipation, diarrhea, and nausea, it also can include anxiety or depression) have reported that they have been doing better after changing to a Paleo diet. 

To help find out why, Kimberly Harer, M.D., gastroenterology fellow at the Center, designed a short-term study.  I recently interviewed Harer and her colleague, epidemiologist Noel Mueller, Ph.D., for Breakthrough, a publication of the Center for Innovative Medicine at Johns Hopkins. 

For two weeks, she says, 40 patients with IBS will be randomly assigned to eat either a Paleo diet or a standard, healthful diet.  Harer and Mueller will be looking at many things in these study participants, including “how the diet affects their GI symptoms, their quality of life, their vitality,” says Harer.  In people who have been experiencing anxiety or depression, the investigators will look for changes in these symptoms, as well.  They will study blood samples and patient responses to questionnaires about their health, and then, looking at the bacteria in stool specimens, the scientists will analyze the gut “microbiome” before and after. 

Let’s just take a moment to reflect on the concept – still fairly new in research – of a microbiome: It’s a small ecosystem made up of bacteria; this is more complex than it sounds.  Just as the earth has its own ecosystems – tundra, tropical rainforests, grasslands – your body has them, too.  Except instead of plants, these microbiomes are populated by bacteria: dozens of them, picky little cliques that only thrive in one particular spot. For example, the bacteria on the inside of your elbow are different from the bacteria on your face – and even on your face, the bacteria on the bridge of your nose are different from the bacteria between your nose and mouth; and those bacteria are different from bacteria on your chin. 

But the gut takes it to another level; it is the microbial mother lode.  In numbers alone, it’s intimidating.  “There are trillions of microbiota (tiny habitats) in the gut,” says Mueller.  And get this:  All of those bacteria in all those micro-habitats have their own genes and their own genomes, which scientists now know how to sequence.  “There are 100 to one more microbial genes than in your own human genome.”

 paleo diet pancakeThis is why scientists at the Amos Center are convinced that the microbiome has an important influence on our health.  It’s not just numbers, it’s sheer mass:  All those bacteria that live inside our gut, if you somehow got them all together in one lump, would weigh and take up about as much space as your brain – three or four pounds.  Trying to get a handle on that would be overwhelming without sophisticated computers and software, sequencing technology, and bioinformatics tools that allow scientists to recognize patterns and identify gene signatures.

Because the study of the gut’s microbiome is still so new, nobody is sure what it’s supposed to look like, and how the gut flora relates to symptoms.  “Maybe we won’t ever be able to define what is the normal gut microbiome,” says Mueller.  “Normal might be different for everybody.”

Even in identical twins, Mueller continues, the bacteria in the gut can be very different.  It is not unheard of for one twin to have a normal weight, and one to be obese. 

Already, at many hospitals gut doctors are waging war with bacteria, successfully treating patients who suffer debilitating diarrhea from recurrent Clostridium difficile (C.diff) colitis with fecal microbiota transplants.  Basically, uninfected fecal material from a relative with healthy gut bacteria is inserted into the patient’s colon, the good bacteria overwhelm the bad bacteria and the C.diff. is conquered. 

In mice, Mueller notes, scientists have found that if they take the microbiota from the fecal sample of an obese individual and inject it into a germ-free mouse, that germ-free mouse will start to become overweight, too.  “The phenotype of obesity can be replicated just through the sharing of bacteria,” he says.  There is a lot of evidence to suggest that gut bacteria play a huge role in diseases of the metabolism – which also suggests that if these bacteria can be changed, there is great potential to improve someone’s health.

In this study, says Harer, “we will look at the microbiome at three different time points.  First, the baseline, before the diet changes; then, after the Paleo or study diet.”  And then one more time: after participants go back to eating whatever they used to eat for four weeks.  Blood samples will be taken after that four-week period, as well, and patients will fill out questionnaires to report any change in their symptoms.

  “If there are differences in the blood and the stool samples, it will be interesting to see if those correlate with changes in their symptoms,” says Harer.  “And we are very interested to see whether reverting back to their old diet causes the former symptoms to come back, or whether there are lasting changes.” 

Certain families of bacteria thrive on a diet full of macaroni and cheese, soda, and ham sandwiches.  Entirely different bacteria could show up if that diet changes to lean meat, nuts, berries, and veggies.  Which raises another question: If someone gets better with the Paleo diet, “what part is the beneficial part?  Is it the lower carbs?  Is it the increase in plants, or in protein content?  Is it cutting out gluten?”  Or is it some new, beneficial bacteria that have taken precedence in the gut?

paleo diet meatIt’s important to remember that “the microbiome is just part of the study,” Harer continues.  “The question is, does this diet improve symptoms in IBS patients?  Unfortunately, there is a huge unmet need in these patients, because there are few effective treatments.”   

Many people who have IBS are not treated very thoughtfully; they get laxatives for constipation, medicine for diarrhea, and often the symptoms don’t go away because the underlying cause is still there.  The Amos Center takes a team approach with gastroenterologists, allergists and immunologists, psychiatrists, nutritionists, and scientists.  Sometimes, Harer says, people who come to the Center are “frustrated, at the end of their rope sometimes when they come to see us.  We use everyone’s input to treat them holistically, and also to try new things.”

One of these new things is a diet so simple that – as the commercials put it – “a caveman could do it.”  If the Paleo diet does indeed help make people with IBS feel better, understanding why it works at gut level is something we’re only beginning to have the scientific knowledge and tools to decipher.

©Janet Farrar Worthington

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Acupuncture, Irritable Bowel, and a “Smart Watch”

Medicine wears off.  If you take a pill, its benefit might last for 12 or even 24 hours, and then you have to take another one.  The same holds true for acupuncture.   Although administered differently – inserting very thin needles through your skin at strategic points – its effects tend to fade just as quickly. 

There’s one big difference:  Most people who get acupuncture only have it once or twice a week, at most. Imagine if you had an antibiotic that worked, and you only took it once a week. 

Jiande Chen, PhD.

Courtesy of Johns Hopkins Medicine

Jiande Chen, Ph.D., a Johns Hopkins biomedical engineer working with the Amos Food, Body, and Mind Center, is about to change this.  I interviewed him recently for Breakthrough, a magazine for the Johns Hopkins Center for Innovative Medicine.

Chen specializes in the pathophysiology of gastrointestinal motility – how food moves through your body — as well as diabetes and obesity.  He is particularly interested in electrical therapies that stimulate the nerves involved in gut function, and now he has developed a novel device for patients to use at home that provides “transcutaneous electrical stimulation” similar to the effect of acupuncture.

In other words, he’s developed a smart watch for acupuncture. 

Requiring only a watch battery, it delivers a painless, noninvasive dose of electric current that penetrates as deeply and precisely as one of those long, thin needles.  But patients can administer it themselves, at home, after every meal. 

It’s safe, DIY home acupuncture, and it might significantly change the way people with certain conditions, starting with gastroparesis, find relief.

In gastroparesis, the stomach is slow to empty.  Food lingers because the muscles that should move it along to the gut – squeezing it like toothpaste through a tube – are either damaged or weak.  One big cause is diabetes.  The condition can be miserable and can include decreased appetite, heartburn, nausea, vomiting, bloating, anxiety, and discomfort.  Symptoms are usually treated with medicine and dietary changes, but in a recent study, Hopkins scientists showed that acupuncture can also help relieve symptoms. 

 Now, let’s switch for a moment and look at gastroparesis as an acupuncturist would. In traditional Chinese medicine, a complex system of healing more than 5,000 years old, practitioners believe our vital energy, called “qi” (pronounced “chee”), flows through the body along 12 pathways, called meridians.  Each meridian involves a different organ system. 

When all is well, the qi flows smoothly; but when there is an imbalance somewhere, the flow is blocked or hindered, and that’s how disease can begin.  The needles inserted during acupuncture are designed to restore this balance.  Gastroparesis might be called “food stagnation,” or “liver and spleen disharmony” in Chinese medicine, but the basic problem would be the same: food not moving through the digestive tract.  The liver is supposed to ensure that everything – digestion as well as emotions – flows smoothly.  When this flow is blocked, it weakens the spleen, which is in charge of digestion.

Acupuncture stimulates nerves – in this case, the vagus nerve, which reaches all the way from the brain down through the esophagus, heart, and lungs, down to the abdomen, and controls many things, including digestion.  It also stimulates blood flow by dilating blood vessels and causes the body to release endorphins, natural painkillers.

In someone with gastroparesis, acupuncture sends a signal to the brain via the vagus nerve, telling the stomach to work better.

Chen’s device works by neuromodulation, using electrical stimulation to change how nerve cells interact. In painstaking research, he has determined the precise levels needed to produce a beneficial change in the function of the nerves – how much energy to release, the speed of the electrical signal, the width of the pulse. 

That precision “is one difference between our method and traditional Chinese medicine.”  Another is frequency:  “It would be very expensive to do traditional acupuncture two or three times a day, but with this device, you are just putting an electrode at the acupuncture points.  You could do it after every meal.”

There are two key placement points:  One is the wrist, “which is very good for treating symptoms like nausea, vomiting, and motion sickness.  That wrist acupuncture point is very close to the medial nerve.” The other is about 5 centimeters below the knee, a place called “stomach point number 36” in acupuncture.  “This is very close to the perineal nerve,” and stimulation here “is known to enhance the autonomic nerve function, which helps empty the stomach and improves the digestive process.”

Basically, Chen explains, “We combined modern neuromodulation theory with traditional Chinese acupuncture.”  This is just the kind of project its leaders envisioned when the Amos Food, Body, and Mind center began a year ago: blending Eastern medicine with state-of-the-art technology in a holistic, whole-body approach to improving health. 

The device has not yet received FDA approval and it doesn’t work for everyone, Chen notes, “but our results of early studies are very exciting.”  In related work, Chen plans to see whether the device can help improve symptoms in patients with scleroderma and whether it can help reduce the appetite in people with obesity.

©Janet Farrar Worthington

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Can Your Gut Bacteria Make You Depressed?

Mr. Rogers' Neighborhood

Gene J. Puskar/Associated Press

If you’re old enough to remember Mr. Rogers, you might remember him singing the happy little song, “So, who are the people in your neighborhood, in your neighborhood, in your neighborhood… they’re the people that you meet when you’re walking down the street.  They’re the people that you meet each day.”

This isn’t Mr. Rogers’ neighborhood.  It’s a lot smaller, but there are some interesting characters here.  They are bacteria, also called gut flora, or microflora.

The microflora in the gut are way more important than anyone realized even a few years ago.  This microbiome is made up of communities of bacteria and other organisms.  Tiny changes here can have big effects — not only on our digestive tract, but on our emotions.

Cynthia Sears, M.D., professor of medicine at Johns Hopkins Medical Institutions, is the director of the Scientific Advisory Board of the new Johns Hopkins Food, Body & Mind Center.  (I wrote about some of the research going on at this center in a recent post.)  In addition to finding links between diet and disease, scientists at the Center, particularly Sears, are studying the role of good and bad bacteria in making us sick and keeping us healthy.

Sears has focused on the many interactions between the gut’s microflora – the little ecosystems of bacteria that live and die down there in without our ever knowing about it – and our health.  I recently interviewed her for Breakthrough, the magazine for the Johns Hopkins Center for Innovative Medicine.  Rapidly expanding evidence, she told me, suggests “that the complex communities that we carry with us, which are on every surface of the body, are essential to health.  But they’re also associated with disease” — both right there in the gut, and distantly.  “They influence liver function, the function of the deep tissues, the enteric nervous system.”  They may also contribute to heart disease, pancreatic conditions, and be linked to our mood and to psychiatric disorders, as well as our weight.  “This concept is amazing,” she says, “particularly the idea that they can influence our mood and how we function in life.”

So, imagine that you have depression, and a doctor has put you on an antidepressant.  And it’s not really helping that much.  Then imagine that a doctor tells you, “the problem could be in your gut.”  This discussion is still pretty new, Sears says, but “our hope is that we will be able to identify the bacteria that produce the right metabolites, the ones that make you feel better,” to change how the microbiome functions.  “So if the microbiome has bad molecules, that we could modify it or treat it in such a way that you get good molecules and change the balance.”

Good bacteria

Photo Credit: sahilsajjad via Compfight cc

I asked her if this might one day eliminate the need for antidepressants.  Probably not, Sears says.  “But there are a lot of people who probably don’t fit into classic psychiatric criteria, who don’t feel well.  So this idea that we can use food and possibly ‘good’ bacteria to modify function and make someone feel better, and help turn someone’s life around, is very intriguing.”

Fermented Foods and Probiotics

Is there anything you can do to help clean up the neighborhood of bacteria in your gut?  Well, yes:  You can eat fermented foods, which contain probiotics, or you can take supplemental probiotics.  The problem with probiotics is that they are not regulated as drugs by the FDA, and there is a lot of variability in quality and effectiveness.  Similarly, there is a surprising lack of definitive, scientific journal-published research absolutely proving that fermented foods are helpful to your health.  However, that said, there is a lot of anecdotal evidence that they are.  The fermented items listed below, eaten in moderation, are not harmful to your health.  You may want to give them a shot for a couple of weeks, and see if you feel better with them in your diet.

Sauerkraut.  It’s fermented, hip, it’s happenin’ — check out the gourmet varieties (like Wildbrine’s Arame Ginger) of sauerkraut in the refrigerated section at upscale grocery stores — and it’s been around since the 4th century B.C.  First of all, it’s cabbage, and cabbage is already good for you, just raw out of the garden.  It’s in the family of cruciferous vegetables, along with broccoli and cauliflower, which have long been shown to help prevent cancer.  But the fermentation process brings some new chemicals to the table, including: isothiocyanates, which counteract carcinogens and help the body remove them; glucosinolates, which activate the body’s anti-oxidants; and flavenoids, which help protect artery walls.  Sauerkraut has few calories.  However, if you eat too much of it, it can cause diarrhea.  Again, moderation in all things.

Kombucha.  Fermented black tea.  Again, we’re starting with something that is already good for you; tea is rich in antioxidants.  Fermented black tea delivers a load of probiotics to your gut.  In addition to aiding digestion, these beneficial bacteria boost the immune system and can relieve irritable bowel symptoms, yeast infections, and other problems.  In one study, rats given kombucha had higher levels of “good” HDL cholesterol, a finding linked to a lower risk of cardiovascular trouble.   FloraStor, a commercial probiotic that’s used to treat C. difficile colitis, was isolated from kombucha.  A study from India found that a form of kombucha was just as effective as the drug, omeprazole (Prilosec), in healing stomach ulcers.  (Note: If you have an ulcer, I wouldn’t chuck Prilosec and start drinking kombucha.  For one thing, the kind you get might not have the kind of bacteria these scientists studied; also, how much would you need to be drinking every day, and for how long?  Ideally, as fermented foods become more popular, they will be better studied and their benefits will become a lot more clear.)

file5321333011701Yogurt.  Look for the words, “Live and active cultures.”  These are probiotics, and besides increasing the number of good bacteria in your gut, they can help reduce symptoms of irritable bowel syndrome, and also can help improve symptoms of inflammatory bowel diseases, such as Crohn’s and ulcerative colitis.  Greek yogurt has more protein than traditional yogurt; it takes longer to digest and can help you feel full longer — which, in turn, can reduce the need for snacks between meals, so as a bonus, it may help you lose weight.

 

 

In addition to the book, I have written about prostate cancer on the Prostate Cancer Foundation’s website, pcf.org.  The stories I’ve written are under the categories, “Understanding Prostate Cancer,” and “For Patients.”  I firmly believe that knowledge is power.  Saving your life may start with you going to the doctor and knowing the right questions to ask.  I hope all men will put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s, and if you are of African descent, or if cancer and/or prostate cancer runs in your family, you need to be screened regularly for the disease.  Many doctors don’t do this, so it’s up to you to ask for it.

©Janet Farrar Worthington

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