Top Six Benefits of Colostrum

Reprinted with the kind permission of Dr. Mercola.

By Dr. Mercola

Your natural immune function is a key component of your health and disease prevention. An integral part of this system is your natural killer (NK) cells, a type of white blood cell important to your innate immune system.1 Your immune system has two branches — cell mediated immunity (innate) and humoral immunity (adaptive).

As you contract a viral illness, the pathogen infects your cells. Immediately, your cell mediated immune response activates NK cells2 along with chemicals to attract the cells to the site of infection. The white blood cells attack the viral cells and destroy them, thus clearing the virus from your body. During the recovery phase, your humoral immune system begins generating antibodies to prevent the same type of infection from occurring again.

Colostrum, the fluid produced by new mothers in the first day or two after birth, plays an integral part in supporting your NK cells,3 as well as affecting inflammation, metabolism and protecting against the development of cancerous growths.

Athletes report improved performance after using bovine colostrum supplements,4 and one of its components demonstrates the ability to stimulate the growth of beneficial bacteria in your gut.5

NK Cells Important in the Prevention of Viral Diseases and Tumors

Before moving further into a discussion of the benefits of colostrum, it’s important to identify the function of NK cells in the immune system and in the prevention of viral diseases and tumors, as this is the foundation of many of the benefits of colostrum. A paper published in Nature describes the functions of NK cells as they are involved in viral disease and tumor treatment:6

“Natural killer (NK) cells are effector lymphocytes of the innate immune system that control several types of tumors and microbial infections by limiting their spread and subsequent tissue damage … NK cells can thus limit or exacerbate immune responses.

Although NK cells might appear to be redundant in several conditions of immune challenge in humans, NK cell manipulation seems to hold promise in efforts to improve hematopoietic and solid organ transplantation, promote antitumor immunotherapy and control inflammatory and autoimmune disorders.”

The process of targeting and killing aberrant viral and tumor cells is mediated by molecules stored in a secretory lysosome, or specialized organelle, found in the NK cells. However, NK cells are not antigen-specific, a process used by your humoral immune response. Instead the NK cells help reduce viral replication as the adaptive arm of your immune system creates antibodies.

A deficiency in NK cells may leave you susceptible to viral infections and, potentially, tumor formation.7,8 Although not antigen-specific, NK cells differentiate between normal healthy cells and aberrant cells, leading scientists to seek ways to enhance NK cell function as a way of improving the effectiveness of cancer treatments.9,10

A recent Stanford study11 discovered a biomarker predicting the susceptibility to flu. Using 52 individuals who volunteered to be infected with influenza, researchers evaluated the types of immune cells present prior to the introduction of the virus and found NK cells were consistently low in individuals exhibiting symptoms of flu and those with higher levels had a better immune response.12

Health Benefits of Colostrum

Many of the benefits of using a colostrum supplement are based on the cellular responses in your body originating from supporting your immune system. Multiple studies have evaluated the use of colostrum in raw milk, including the effects on body composition, metabolism, recovery from surgery and protection against viral diseases, including rotavirus responsible for diarrheal illnesses.13

Colostrum is a critical nutrient source for the development of infants. Feeding formula, which does not contain colostrum, is believed to increase an infant’s risk of Type 1 diabetes, childhood cancers, colitis, allergies and chronic infections.14

The bioactive molecules in colostrum helps modulate an infant’s immune system and avoid over growth of pathogenic microorganisms. In adults, colostrum has been shown to affect:15,16

Allergy and infection — In a mouse study,17 researchers supplemented the experimental group with colostrum and then infected the control group and experimental group with the influenza virus. The mice supplemented with colostrum lost less weight and had a lower viral burden in the lungs compared to the control group.

The researchers then used a primary culture of small intestine epithelial cells stimulated with colostrum and discovered an interaction was potentially dependent on the components of colostrum with receptors in the intestinal epithelium.18

In another study,19 50 percent of orally ingested bovine immunoglobulin G protein (IgG, an antibody molecule) has been recovered in feces having passed through the gastrointestinal tract. The recovered levels in infants are higher than adults, likely due to differences in intestinal conditions, including pH.

Researchers believe this indicates bovine IgG is functionally active throughout the intestinal tract, helping to prevent gastrointestinal tract infections and lipopolysaccharide-induced inflammation.

IgG present in colostrum binds to human pathogens and allergens, neutralizing infection and limiting gastrointestinal inflammation. Researchers theorize the immunoglobulins may be a promising approach to supporting immune function and reducing allergic reactions.

Inflammation — Colostrum is rich in proline-rich polypeptides (PRPs), which have immune regulatory properties, appearing to restore balance and cellular functions. PRP has a regulatory activity in cytokine induction and inhibits the overproduction of reactive oxygen species and nitric oxide.20

PRPs also help relieve swelling by offsetting an overly active immune response and halting responses characteristic in rheumatoid arthritis and fibromyalgia.21 PRPs may also decrease the severity of an inflammatory disease by altering genetic expression.22

The polypeptides have been shown to improve cognition and behavior in older rats, humans and chickens.23 Additionally, the presence of lactoferrin in colostrum plays a role on the development of inflammation. This protein plays a crucial role in iron homeostasis24 and has been shown to inhibit autoimmune responses that trigger inflammation.25 Lactoferrin is a strong antioxidant aiding the body in detoxification and helping decrease the toxic load on your lymphatic system.26

Cancer — The extraordinary effect colostrum has on immunity has translated to the ability to help fight cancer. The combination of inhibiting autoimmune responses, reducing inflammation in the gut and reducing infections is part of the process. Bovine colostrum activates the production of GcMAF, responsible for repairing tissue damage and preventing the growth and spread of cancer.27

Metabolism — Colostrum has also been used in patients with insulin resistance, which can lead to liver injury. In one animal study,28 researchers evaluated the effect hyperimmune colostrum had on hepatic injury and insulin resistance after oral administration.

Glucose intolerance and liver enzymes improved and the mice experienced a reduction in serum tumor necrosis factor, suggesting hyperimmune colostrum preparations help reduce chronic inflammation, liver injury and insulin resistance associated with nonalcoholic steatohepatitis.

Healthy gut — A critical action associated with colostrum growth factors is healing and prevention of damage to the gastrointestinal lining by maintaining tight junctions between the cells. Colostrum helps reduce symptoms of leaky gut syndrome,29 which allows large or partially digested food proteins to pass into the body and trigger an inflammatory response.

The antibodies and lactoferrin help maintain a healthy microbiome, largely responsible for your overall health and wellness.30 Lactoferrin also acts as a prebiotic, stimulating the growth of specific good bacteria.31

Body composition — The high number of antioxidants and growth factors in bovine colostrum has made it a powerhouse for promoting muscle growth and healing ligaments and muscles after injury. Reduction in oxidative stress and overall damage after exercise has made it a supplement of choice for Olympic athletes to support their performance.32

In one study,33 athletes increased their lean muscle mass and performance after eight weeks of using colostrum supplements. The Center for Nutritional Research34 states the growth factors in colostrum are used by athletes to help burn fat, build strength, shorten recovery time and prevent illness after a vigorous exercise program.

In a consensus statement, the International Olympic Committee35 ruled colostrum is a superfood and a legal alternative to banned substances to improve athletic performance.

Veterinarians Use Colostrum to Treat Dogs and Horses

Veterinarians have been using bovine colostrum to treat dogs and horses therapeutically as it provides over 70 different growth factors for tissue repair. Dog owners have used colostrum to help reduce canine allergies, improve leaky gut and externally in the treatment of wounds.36 According to Biostar Whole Food supplements, it’s used:37

  • To support the immune system and homeostasis, especially when dogs and horses are experiencing stress-related immune issues
  • For tissue repair, wound healing and GI tract healing
  • For muscle restoration
  • For some senior animals who have ongoing issues

Hyperimmune Bovine Colostrum in Clinical Trials

Colostrum contains proteins, carbohydrates, fats, vitamins and minerals used by the baby to help fight disease and nourish the body. Antibody levels in colostrum may be up to 100 times higher than levels in regular milk.38

Researchers have now created a special type of colostrum called hyperimmune bovine colostrum, produced after the cow receives a vaccination against a specific organism. The cow develops antibodies against the organism, which is then passed along in the colostrum.

Today, hyperimmune bovine colostrum is being used in clinical trials to test the treatment for diarrhea related to AIDS,39 graft-versus-host disease40 and Clostridium difficile.41

The U.S. Food and Drug Administration (FDA) has granted orphan drug status42 to hyperimmune bovine colostrum. This gives drug manufacturers who invest special market advantages, such as permission to sell the drug without competition for seven years.

Steer Clear of Colostrum When You’re Fasting

It’s important to remember, while there are benefits to using colostrum, the product is rich in growth factors. Athletes use it to boost performance and it may be used to help treat wounds. This means, while you’re fasting and trying to induce autophagy, it’s important to steer clear of colostrum.

Autophagy is a process your body uses to help to clear damaged cells,43 including old cells no longer serving a functional purpose. The word is derived from Greek words “auto,” meaning self, and “phagy,” meaning eating. In recent studies researchers have observed how this process promotes longevity and benefits the nervous system, heart and metabolism.44

You may help induce autophagy through the practice of fasting, which helps clear old cells from your body and improve your overall health. The use of colostrum during this process is contraindicated, as the growth factors increase growth at the same time your body is attempting to clear old cells.

More Ways to Naturally Boost Your NK Cells

Researchers continue to place their hope in finding an effective flu vaccine, but you don’t need drug intervention to boost your NK cells and therefore your protection against virtually all viruses and malignancies. NK cells tend to lose utility with increasing age, leaving you more susceptible to disease. The medical term for this degeneration is “immune senescence.”

The good news is you may counteract this decline using a number of different strategies and lifestyle choices, one of which is using a colostrum supplement. However, there are 10 more strategies you’ll find in my previous article, “How to Improve Your Immune Function by Boosting Natural Killer Cells.”

This article was brought to you by Dr. Mercola.

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Chronotropic Intolerance: An Overlooked Determinant of Symptoms and Activity Limitation in ME/CFS?

Chronotropic Intolerance: An Overlooked Determinant of Symptoms and Activity Limitation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?

Abstract

Post-exertional malaise (PEM) is the hallmark clinical feature of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). PEM involves a constellation of substantially disabling signs and symptoms that occur in response to physical, mental, emotional, and spiritual over-exertion. Because PEM occurs in response to over-exertion, physiological measurements obtained during standardized exertional paradigms hold promise to contribute greatly to our understanding of the cardiovascular, pulmonary, and metabolic states underlying PEM.

In turn, information from standardized exertional paradigms can inform patho-etiologic studies and analeptic management strategies in people with ME/CFS. Several studies have been published that describe physiologic responses to exercise in people with ME/CFS, using maximal cardiopulmonary testing (CPET) as a standardized physiologic stressor. In both non-disabled people and people with a wide range of health conditions, the relationship between exercise heart rate (HR) and exercise workload during maximal CPET are repeatable and demonstrate a positive linear relationship.

However, smaller or reduced increases in heart rate during CPET are consistently observed in ME/CFS. This blunted rise in heart rate is called chronotropic intolerance (CI). CI reflects an inability to appropriately increase cardiac output because of smaller than expected increases in heart rate. The purposes of this review are to (1) define CI and discuss its applications to clinical populations; (2) summarize existing data regarding heart rate responses to exercise obtained during maximal CPET in people with ME/CFS that have been published in the peer-reviewed literature through systematic review and meta-analysis; and (3) discuss how trends related to CI in ME/CFS observed in the literature should influence future patho-etiological research designs and clinical practice.

Source: Todd E. Davenport, Mary Lehnen, Staci R. Stevens, J. Mark VanNess, Jared Stevens and Christopher R. Snell. Chronotropic Intolerance: An Overlooked Determinant of Symptoms and Activity Limitation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Front. Pediatr., 22 March 2019 | https://doi.org/10.3389/fped.2019.00082 (Full article)

A Former Doctor Goes Through the NIH’s ME/CFS Intramural Study

Reprinted with the kind permission of Simmaron Research.

By Cort Johnson

Robert’s Story

Robert, an MD, is board certified in internal medicine. After the worst flu-like illness he ever had, he ended up in the hospital. A regular exerciser prior to becoming ill, his legs were so weak that he could hardly walk afterwards.

His path to a chronic fatigue syndrome (ME/CFS) diagnosis was rapid. Three months of testing left him no other conclusion – it was clear to him that he had ME/CFS. He was able to work on and off for a few years, but his health has deteriorated. He’s been unable to work for the last three years.

Thankfully, he had a wide array of doctor friends who knew him before he became ill and didn’t encounter the skepticism and invalidation so commonly experienced in our community. He noted that our current medical culture doesn’t offer much for the complex patient. Doctors are busy and often time-constrained and if you don’t fit into one of the medical pigeon-holes, they don’t have much to offer.

Rating his level of health on a scale of 1-10 at 2, he’s one of the sickest, if not the sickest, ME/CFS patient to participate in the grueling two-part intramural study at the NIH. He was the first patient to go through the second phase of the Intramural trial which involved, among other things, the exercise study and an extended stay in a metabolic chamber.

One theme – validation – cropped up several times during Robert’s week long stay at the NIH hospital in Maryland. It was clearly apparent from the gestures of sympathy from the occupational therapist during a test to assess functioning. Given cards which identified an activity, Robert put them into two piles – activities he used to do and activities he still did. The occupational therapist – who has probably given this test hundreds if not thousands of times – registered dismay at the few cards left in his “still do” pile. Those few cards left made the extra level of devastation that ME/CFS is so good at causing clear. It’s rare for people who are not elderly to be so sick.

Given his abysmal level of functioning, Robert’s willingness to participate in a study that Dr. Nath thought few might be willing to undergo was a real testament to the courage and determination that so impressed Dr. Nath. Despite Robert’s low functional level (1-2 on a 10-point scale), he was disappointed that the NIH was not doing a two-day exercise test (!).

The second part of the study is centered around the exercise stressor. Participants do cognitive testing, blood tests, the Seahorse mitochondrial test, a functional MRI and transcranial magnetic stimulation before and after the maximal exercise test. (The NIH communicated with the Workwell Foundation on doing the exercise test with ME/CFS patients).

Exercise is finally getting its due in ME/CFS, and over the next couple of years several large studies should tell us much. With its extensive blood draws and millions of data points, Dr. Klimas’s exercise studies have informed her models of ME/CFS and laid the foundations for her clinical trial. With help from the Solve ME/CFS Initiative, David Systrom has added gene expression to his already complex invasive cardiopulmonary exercise testing. Maureen Hanson has incorporated exercise into her large NIH Research Center studies at Cornell, as well. None of these studies, though, can match the sheer breadth of this NIH exercise study with its brain scans, lumbar punctures, Seahorse data, blood draws, etc..

Metabolic Chamber

Robert spent about three days in the metabolic chamber – a sparse box containing a bed and a toilet that’s designed to produce precise measures of metabolic activity – before and after the exercise test. (I will expand on the metabolic chamber). He wore an EEG, blood pressure and Holter monitor, while in the chamber.

Only thirty metabolic chambers exist in the world, and three of them are at the NIH. With 400 metabolic chamber studies underway every year, they’re pretty much in use all the time. These airtight 11-by-11.5-foot rooms aren’t much to look at or stay in: they come with a bed, an exercise bike, a toilet, and nothing else. Precisely measured meals are delivered through a small, air-locked opening in the wall.

Metal pipes running along the ceiling that measure oxygen consumption and CO2 production allow researchers to precisely calculate an individual’s metabolic rate. From the O2 and CO2 readings, researchers can calculate calories burned and what type of fuel (carbs/fats) was used to burn them. Urine is collected to assess protein oxidation.

Metabolic chamber studies have demonstrated how flexible the body is with respect to metabolism. One reporter wrote, for instance, that they’ve debunked the idea that ketogenic diets (high-fat/low-carb) cause the body to burn more fat than high-carb diets.

Energy is burned in our body in three ways. It turns out that simply staying alive is pretty energy intensive. Most of the calories we burn (65-80%) are used simply to keep our body running (basal metabolism). Digestion is no walk in the park either; digesting our food takes up about 10% of the calories we burn in a day, with physical activity accounting for the remainder (10-30%).

If ME/CFS patients’ metabolic production and ability to produce energy is altered by exercise – as Workwell’s and Dr. Keller’s tests suggest it is – that will hopefully be picked up by the metabolic chamber.

Robert noted that if they can pair the findings from the metabolic chamber – which is measuring the metabolic effects of exercise – with the Seahorse tests- which are measuring energy production on the cellular level, they may really be onto something.

Brain Scan

The functional MRI – which Robert said was combined with a cognitive test – will assess the impact of exercise on a) cognitive functioning and b) brain functioning. A similar study by the CDC suggested that exercise negatively impacted both cognitive and brain functioning.

People who do cognitive tests tend to improve the more they do them but not in this case – not in people with ME/CFS after exercise. Familiarity did not breed more competence. Despite doing the tests multiple times, the people with ME/CFS did worse and worse on them after exercise and the brain scans indicated why. Exercise had knocked out one area of the brain devoted to sustained attention causing the brain – in a mostly futile attempt to compensate – to increase activity in other parts of the brain (devoted to executive functioning).

The end result was that people with ME/CFS expended more effort during the cognitive test and yet did worse. By the end of the test they were making about double the errors of the healthy controls.

The repetitive transcranial magnetic stimulation (rTMS) test proved enormously interesting but physically draining. Robert reported that in a process that took hours, data from a previous fMRI was used map the exact location of his motor cortex in order to stimulate the muscles of his right hand/fingers. The goal was apparently to determine the speed at which the signal traveled from the brain to the muscle of his finger before and after exercise. A time delay after exercise would presumably indicate that exercise had interfered with the ability of the motor cortex to activate the muscles.

A 2003 study, in fact, suggested that reduced muscle recruitment due to reduced motor cortex output was occurring in ME/CFS. The motor cortex, it turns out, plans our movements in advance. The study, titled “Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome“ suggested that problems in the “motor preparatory areas of the brain” might be hampering physical movements in ME/CFS. It has never to my knowledge been followed up on.

rTMS has relieved pain in fibromyalgia but it had the opposite effects in Robert. He wasn’t clear whether it was the effects of the rTMS or the rigors of setting up the test itself or both which triggered for him what turned out to be an extraordinary bout of PEM (post exertional malaise). The 2 hours it took – sitting up – to get the electrodes correct was in itself draining. (He suggested that they use a reclining chair for future patients if possible.)

At the end of test Robert felt exhausted and experienced transient vertigo, auditory disturbance, headache and sensitivity to light and noises. His nurse was shocked at how poorly he looked. He’d mentioned the documentary Unrest to her the day before. After seeing the movie, she said she could better appreciate what he was going through. (Hopefully she knows that watching the film will get her continuing medical education (CME) credits)

The rTMS test proved immediately much more exhausting than the exercise test, the effects of which took a day to kick in. The rTMS specialist/researcher was surprised at the effect the test had on Robert and its cause is unknown. Was it the long preparatory period or the activity of the rTMS machine on the muscle activation pathways or both? It’ll be fascinating to see how other patients fare.

Robert was also tested for small fiber neuropathy via skin biopsy, underwent a post exercise lumbar puncture and quadricep muscle biopsy. The possibility of integrating the brain scan, cerebral spinal fluid, Seahorse and metabolic chamber results after exercise – not to mention the immune tests – is an enticing one for sure.

Plus there are the muscle biopsy results. Robert’s experience of a rather hefty muscle biopsy suggests that the NIH is not stinting on this area – which Dr. Nath believes may tell us much about ME/CFS.

Plenty of rest periods were provided during the study but at times the testing was lengthy, and the study, predictably, ended up being a rather grueling seven days for this courageous but very disabled ME/CFS patient. Participating in it wasn’t easy but the fact that Robert, even with his abysmal level of functionality, made it through it and recovered, was a good sign. Robert said he was touched by a chaplain who stopped by to see how he was doing.

He’s stayed in touch with the investigators from time to time alerting them of developments in the ME/CFS field.

Participating in the Study

The NIH needs more participants. If you’re interested in helping to further ME/CFS research by participating in the study, check out the study criteria below.

All participants must be 18-60 years old and have at least a 7th grade education. People whose ME/CFS started after an episode of infection and who have severe symptoms lasting from 6 months to 5 years are eligible to participate in the study.

Find out how to participate here.

The Brainstem, Vagus Nerve, Neuroinflammation and Chronic Fatigue Syndrome: The VanElzakker Way

Reprinted with the kind permission of Simmaron Research.

By Cort Johnson

In 2013, Michael VanElzakker produced one of the most intriguing hypotheses to date in ME/CFS. His Vagus Nerve Hypothesis proposed that an infection/inflammation near the vagus nerve was causing it to send an unending stream of messages to the brain, telling it to essentially shut the body down by producing fatigue, pain and other symptoms. Since then, he’s been particularly interested in the connection between the vagus nerve, the brainstem and the ME/CFS.

He’s not the only one interested in the brainstem. In 2019 once his brainstem compression was alleviated, Jeff completely recovered from his severe ME/CFS, POTS and MCAS. Since he published his story over a dozen people have been diagnosed with craniocervical instability – a condition which compresses the brainstem.

In this critical review paper, VanElzakker et. al. pick apart some of the research done and provide a guide to successfully getting at the brainstem and other regions of the brain. It’s called a “Critical Review” and is critical, indeed. It finds many past ME/CFS studies wanting, but then points a way to a better possible future. If brainstem problems play a role in ME/CFS these researchers demonstrate how to get at them.

Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods. Michael B. VanElzakker, Sydney A. Brumfield and Paula S. Lara Mejia. Front. Neurol., 10 January 2019 https://doi.org/10.3389/fneur.2018.01033 https://www.frontiersin.org/articles/10.3389/fneur.2018.01033/full

First, VanElzakker et. al. examines one of the sacred cows in the chronic fatigue syndrome (ME/CFS) community – the preferred term for so many: myalgic encephalomyelitis (ME), which refers to muscle pain (myalgia) related to central nervous system inflammation (encephalomyelitis).

While muscle pain is common, it’s not universal. Even people with severe ME may not report pain.

Still, the core part of the definition deals with central nervous system inflammation – a description that, with the emergence of the 2015 Yakatomi and the 2019 Younger studies, seems more and more likely to stick. (A 2018 PET scan study also found neuroinflammation in fibromyalgia as well.)

The idea that inflammation plays a key role in this illness makes sense, given the infectious trigger so commonly (but not universally) found. The authors are just a few among many (Avindra Nath, Jarred Younger, Andrew Lloyd and others) who believe that an infectious event has triggered changes in the brain that are producing fatigue, pain and other problems in ME/CFS.

They point to three ways an infectious trigger could produce central nervous system inflammation in ME/CFS:

A) immune factors (e.g. cytokines) triggered by the infection could get transported across the blood-brain barrier (BBB) that protects the brain. The normally taut blood–brain barrier makes blood-borne infections of the brain rare, but it can, like the gut, become leaky in inflammatory states, allowing immune factors and pathogens entry. Once in the central nervous system, they could trigger a large inflammatory response, or

B) High concentrations of immune factors could allow pathogens to passively diffuse across the BBB, or

C) Immune factors in the blood could trigger the vagus nerve to send signals to the brainstem and brain, which then sparks an inflammatory response.

It’s the last option that primarily concerns these authors. VanElzakker is the author of the Vagus Nerve Hypothesis, which proposes that an infection/inflammation near the vagus nerve is causing it to send an unrelenting stream of signals to the brain, telling it to produce the flu-like symptoms that constitute “sickness behavior” (withdrawal to bed), which isolates infected people from the community and keeps them from spreading an infection.

The largest nerve in the body, the vagus nerve transmits sensory, autonomic, immune and other signals to the brainstem – making it potentially a key player in a possible neuroinflammatory disease like ME/CFS.

Studies indicate that inflammation in the periphery tends to produce a mirror inflammatory response from the immune cells (the glia) in the brain. Even small levels of cytokines in the periphery or body have the potential to activate the chemoreceptors in the vagus nerve, which then activate the immune system in the brain.

That brain activation, interestingly, tends to occur in regions (basal ganglia, limbic system organs (amygdala, hippocampus and hypothalamus), anterior cingulate cortex, prefrontal cortex, and thalamus), which studies suggest are also involved in ME/CFS.

The authors believe the brainstem (which, as it name implies, is found at the very base of the brain, above the termination of the spinal cord), could play a key role in chronic fatigue syndrome (ME/CFS) for four reasons:

  1. Immune signals from the vagus nerve to the brain travel through the brainstem.
  2. The brainstem is dense with mast cells, and mast cell activation syndrome (MCAS) appears to be common in ME/CFS.
  3. The brainstem regulates autonomic nervous system functioning – a common trouble area for ME/CFS and related disorders.
  4. The brainstem also regulates immune functioning; in particular, it triggers an anti-inflammatory response that should limit the inflammatory response.

Whether caused by a structural problem (as in Jeff’s case), inflammation or an infection, the brainstem is a centrally placed brain component that produces many of the issues in ME/CFS.

Seeing the Brainstem in Chronic Fatigue Syndrome (ME/CFS)

Consistent inflammation of the brainstem has not, however, been found in ME/CFS. The authors argue, though, that researchers have rarely used the right kind of imaging needed to investigate this.

The most commonly used method for measuring inflammation in the brain involves measuring the 18kD translocator protein (TSPO) with a PET scan. This protein is produced when the immune cells of the brain – the microglia – become activated. Because the microglia are the chief producers of inflammation in the brain, the TSPO provides a reliable way to indirectly measure neuroinflammation and its effects.

The Nakatomi Study

Nakotomi’s small ME/CFS study using TSPO made a big splash in 2014. Tony Komaroff called the finding of central nervous system inflammation the most important study in decades. Five years later, Van Elzakker et. al. called it “important” and potentially “groundbreaking”. The study used TSPO imaging to find widespread neuroinflammation, particularly in the areas leading from the brainstem to the thalamus.

While the authors regard Nakatomi’s study as potentially groundbreaking, the study is not without significant issues. The authors, in fact, seemed a bit shocked that Nakatomi found as many effects as he did, given the techniques used.

The neuroimaging techniques Nakatomi used (and which most researchers use) were not designed to address brainstem inflammation. Nakatomi used a spatial “registration” technique that aligns the image on the neocortex or upper part of the brain. This kind of alignment is typically done because researchers tend to focus on the upper, “higher” functioning areas of the brain. It can, however, impair the sensitivity of imaging done on the lower, more densely packed, primitive areas of the brain, such as the brainstem, and lead to false negatives.

Nakatomi also used an older tracer (PK-11195) which does not penetrate deeply into the brain and can bind to unintended elements in the brain. Differences in blood-brain barrier permeability between the ME/CFS patients and healthy controls – a distinct possibility – could have confounded the results, as well. Nakatomi’s use of the cerebellum as a kind of baseline measure could have introduced further issues if problems with the cerebellum (another possibility) exist in ME/CFS.

Plus, the hypometabolism believed present in ME/CFS could have resulted in lower amounts of the tracer being metabolized than usual – causing higher amounts of the tracer to reach the brain – and producing a false positive. Because exercise may affect how much of the tracer is taken up into the cells, Nakatomi’s use of healthy, non-sedentary controls instead of sedentary controls introduced another issue.

Finally, because the brainstem actually pulses with every heartbeat, that movement needs to be accounted for – and usually isn’t in ME/CFS studies. The very small but important nuclei in the brainstem are also often not picked up with the standard imaging techniques used in ME/CFS research.

Nakatomi’s study results make sense given what we know, and were given a sort of validation by Jarred Younger’s recent results using thermal mapping – a new technology – but we need more validation.

The takeaway is that the brainstem – because of the role it plays in autonomic nervous system functioning, immune regulation and the transmission of motor signals – could play a major role in ME/CFS, but is essentially, according to these authors, still something of a black box.

Barnden’s Brainstem – the Australian Study

It’s not completely a black box, though. Researchers using other techniques have found evidence of brainstem problems in ME/CFS. Barndem in Australia, in particular, has done a series of MRI studies which have found striking brainstem issues in ME/CFS.

(During his talk at the 2019 Emerge conference, Barnden noted how he had to shift his MRI to avoid the alignment problem (that VanElzakker mentioned) which prevented him from getting a good image of the brainstem. )

One study found that reduced brainstem grey matter volume – suggesting that damage to the neurons in the brainstem had occurred – was correlated with autonomic nervous system problems in ME/CFS.

Another study finding of impaired communication from the brainstem nuclei to other nuclei in the brain suggested the same, and found increased signs of myelination in the sensorimotor cortex of the brain. Barnden proposed that decreased signaling from a damaged brainstem provoked a compensatory increase in myelination in the sensorimotor region as it bulked up to try to understand the limited signaling coming from the brainstem. The impaired brainstem-sensorimotor connection might be, Barnden thought, impacting motor functioning in ME; i.e. the ability to carry out physical activity.

Signals to move muscles pass from the motor cortex to the sensorimotor cortex down to the thalamus and then through the brainstem to the muscles. (Signals from the muscles to the brain pass up through the same pathways.) Barnden proposed that the movement problems in ME/CFS could start with the brainstem’s inability to properly relay signals to the motor cortex to activate the muscles.

Barnden’s most recent brainstem study validated the idea that inadequate communication between the brainstem nuclei and other nuclei in the brain, including the vasomotor region, hypothalamus and prefrontal cortex, was affecting autonomic nervous system functioning in ME/CFS.

Other Kinds of Brain Scans

Other kinds of brain scans, such as magnetic resonance spectroscopy (MRS), can pick up signs of neuroinflammation. Although almost 10 MRS studies of the brain in ME/CFS have been done, VanElzakker et. al. report that a clear and consistent picture of metabolite alterations in the brain has yet to emerge.

They believe that’s due largely to a common theme in medical research, found in this disease in particular – lack of standardization. Different diagnostic criteria, different types of healthy controls, different brain regions examined, and different metabolites targeted make it difficult to present a clear picture of the metabolic alterations in the brains of people with ME/CFS.

The Japanese Take

The Japanese probably couldn’t agree with Barnden more. Their studies indicate that, as the healthy controls became more fatigued, two core regions – both of which communicate with the brainstem ( the prefrontal cortex and the anterior cingulate cortex) – shut down.

As these regions begin to shut down, control of autonomic functioning becomes lost. In particular, the ability to activate the parasympathetic nervous system (i.e. the vagus nerve) and tone down the sympathetic nervous system activity, is lost.

The Japanese believe a breakdown in what they call the facilitation system in the brain has occurred. As we become fatigued, the facilitation system jumps in to increase the signals coming from the primary motor cortex to the muscles. This increased “drive” from the motor cortex prompts the muscles to work harder and activates more and more of them so that activity can proceed.

So long as new, fresh muscle fibers remain to be recruited, the activity can continue. If no muscle fibers are left to be recruited or if the brain has a problem recruiting new muscle fibers, fatigue sets in.

A 2003 study suggested that reduced muscle recruitment due to reduced motor cortex output was indeed occurring in ME/CFS. That study suggested that, “… changing motor deficits in CFS has a neurophysiological basis [which] … supports the notion of a deficit in motor preparatory areas of the brain”. That study titled, “Deficit in motor performance correlates with changed corticospinal excitability in patients with chronic fatigue syndrome“, to my knowledge was never followed up on.

Conclusion

Several studies suggest significant brainstem issues may be present in ME/CFS. Problems with the brainstem could produce everything from autonomic nervous system problems to immune issues to problems with movement.

The authors critique past brain imaging studies and provide a “how to” guide to assess the brainstem in ME/CFS. Barnden’s Australian brainstem studies suggest that when done correctly, MRI imaging studies may indeed find extensive damage is present in ME/CFS. Barnden found evidence of brainstem neuron demyelination, a compensatory remyelination in parts of the brain the brainstem connects with, and lastly, a reduced connectivity between these regions in ME/CFS.

VanELzakker et. al. assert that future imaging studies that focus on the specific functional connectivity pathways in the brain which are activated by inflammatory processes should be able to capture the neuroinflammatory processes occurring in ME/CFS. (Two of the three pathways they cite include the brainstem.) The thalamus’s role in sensory stimuli activity presents another fruitful pathway to assess. Lastly, the authors suggest that researchers target the nucleus of the solitary tract (NTS) where the vagus nerve enters the brainstem.

With help from an ME/CFS donor, VanElzakker has been employing brain imagining techniques to assess the brainstem in chronic fatigue syndrome (ME/CFS). He will be speaking at the NIH ME/CFS Conference in Baltimore in April.

Marjoram: A Versatile Herb for Cooking and Aromatherapy

Reprinted with the kind permission of Dr. Mercola.

The marjoram plant (Origanum majorana) is an aromatic herb known for its aromatherapeutic and culinary uses. Its botanical name literally means “mountain beauty.” Interestingly, since marjoram and oregano (Origanum vulgare, which means mountain joy when translated), have often been confused through the years, you may also see marjoram referred to as mountain joy.

In Greek mythology, Aphrodite was believed to have grown this herb, as well as oregano. Romans, on the other hand, believe marjoram was made by Venus.1

Marjoram is classified as a perennial, and can grow up to a height of 24 to 36 inches. It’s closely related to (and often confused with) oregano, because of their similar appearances, most notably because of their oval, flat green leaves.2

To make things even more confusing, as mentioned, their botanical names are quite similar. But even more confusing, Origanum vulgare, which is the common oregano, is also known as wild marjoram. Since it can be very confusing, be sure to do your research before you purchase either of these plants.3

The 6 Health Benefits of Marjoram You Should Know About

Marjoram can be used in cooking or in aromatherapy, in its essential oil form. That being said, depending on how it’s used, marjoram is known to provide the following health benefits:

  1. Antioxidants — A 2005 study showed that marjoram contains various antioxidants. Most notably, Egyptian varieties contained more antioxidants compared to Hungarian ones.4
  2. Antimicrobial — Extracts of marjoram have been found to be effective against several species of fungi and bacteria.5
  3. Anti-inflammatory — In vitro examination of marjoram showed that it may help manage inflammation. Researchers discovered that the plant suppressed pro-inflammatory cytokines. Sabinene hydrate and terpineol have been identified as the main anti-inflammatory compounds.6
  4. Better digestion — A mice study showed that marjoram extract exhibits antiulcer properties, as well as reducing basal gastric secretion and acid output. In addition, marjoram may help repair the gastric mucosa.7
  5. Reduced risk of cancers — A PLOS One study showed that marjoram has promising potential in modulating breast cancer growth and metastasis.8 Another study shows that marjoram extracts have beneficial effects against human lymphoblastic leukemia cell line.9
  6. Better heart health — A study found that marjoram helped alleviate erythrocytosis, granulocytosis, thrombocytosis and myocardial oxidative stress, as well as other cardiovascular factors.10

4 Ways to Use Marjoram Effectively

The beauty of marjoram is that it can be added to various dishes and can be used for different cooking methods, such as:

  1. Soups — It gives vegetable soups more flavor.11
  2. Roasted meats — Marjoram can add an herbal aroma to roasted meats, such as chicken.12
  3. Sautéed vegetables — Side dishes such as sautéed vegetables become more flavorful with a dash of marjoram.13
  4. Marinades — Upgrade the taste of your marinated meat and fish dishes by adding marjoram to the marinade.14

Planting marjoram in your garden can reap benefits as well. Not only does it create a beautiful atmosphere, but it also helps attract butterflies and other insects that feed on pests and decomposing matter, and can even pollinate plants.15,16

Oregano can be used as a substitute for marjoram if you don’t have it at the moment. But remember that although these two plants are very similar in appearance, they do have slight differences in flavor. Oregano has a pungent, spicy taste, while marjoram is sweeter and floral. If you want to use oregano in place of marjoram, only use a small amount to mellow out its strong taste.17

Growing Marjoram in Your Home

Marjoram is quite easy to grow in the comfort of your own home. It can be placed in an indoor container, window box or outdoors in your garden.

Start by making sure your soil has good drainage. Sunlight exposure must be at its fullest for the plant to grow well.18 Plant marjoram seeds during the late winter or early spring, because the extremely cold temperatures will damage the plants and may even cause seedlings to die out.19

If you’re just starting out, plant indoors first and when the snow has melted, you can transfer your site outdoors. Make sure that the location has plenty of sunlight, and the soil follows the appropriate conditions.20

Start planting seeds by placing them just beneath the surface of the soil. As the seedlings grow, remember to clear up space by placing each of them 10 inches apart in all directions. The plants are ready for harvesting once they reach a height of 3 inches. To get the best flavor, pick them before the flowers start to open.

Once picked, dry them to seal in their taste and aroma. Simply group plants in small bundles and hang them upside down in a dark room with good ventilation. Afterward, remove the stems, then crush or grind before using.21

Try This Healthy Recipe: Spicy Roast Chicken With Tomatoes and Marjoram

This recipe from Bon Appétit uses marjoram to provide roast chicken with a wonderful aroma and flavor. With the addition of tomatoes and red pepper, this dish is not only delicious, but warm and inviting as well.22

Ingredients

4 pasture-raised chicken breast halves with ribs
24 ounces cherry tomatoes (about 4 cups), stemmed
1/4 cup coconut oil
5 garlic cloves, pressed
1 1/4 teaspoons dried crushed red pepper
2 tablespoons chopped fresh marjoram
Himalayan salt and freshly ground pepper, to taste

Procedure

  • Heat the oven to 450 degrees Fahrenheit.
  • Toss the tomatoes, coconut oil, garlic, crushed red pepper and a tablespoon of marjoram in a large bowl.
  • Place the chicken slices on a rimmed baking sheet.
  • Pour the mixture over the chicken, while arranging the tomatoes in a single layer on a sheet around the chicken.
  • Sprinkle the chicken slices generously with salt and pepper.
  • Roast until the chicken slices are cooked through and the tomatoes are blistered, for about 35 minutes.
  • Transfer the chickens to plates.
  • Spoon the tomatoes and juices over.
  • Sprinkle the plates with the remaining tablespoon of marjoram and serve.

Marjoram Essential Oil Has Unique Benefits, Too
Marjoram oil has been a popular fixture in folklore medicine for a long time. Research shows that it has been used as an antimicrobial as well as anti-inflammatory. A 2017 study summarizes the main possible benefits of marjoram essential oil:23

  • Antioxidant
  • Antimicrobial
  • Anticancer
  • Anti-inflammatory
  • Hepatoprotective

How to Make Marjoram Essential Oil

Modern manufacturing of marjoram essential oil is achieved through steam-distilling the tops of the plant. Depending on the source, the final product is a yellow to yellow-green oil. Spanish varieties produce an orange color.24

Using Marjoram Essential Oil Properly

Before using marjoram essential oil (or any essential oil), you need to be aware of any potential allergic reactions. If you have any pre-existing medical conditions or are pregnant, it’s important to consult with your doctor first and let them know of your intention to use marjoram essential oil.

Once you’ve gotten permission from your doctor, do a skin patch test on your arm with a drop of the oil and check for any allergic reaction or irritation. Should a negative reaction occur, stop using the oil immediately.

This article was brought to you by Dr. Mercola.

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Vitamin B12 deficiency could increase risk of infection

Reprinted with the kind permission of Life Extension.

March 18 2019. An article published on March 13, 2019 in PLoS Genetics describes a study involving the roundworm Caenorhabditis elegans (C. elegans) which uncovered a link between insufficient dietary intake of vitamin B12 and a greater risk of potentially lethal infections. Caenorhabditis elegans are similar to humans in their need to obtain vitamin B12 by dietary means.

“We used C. elegans to study the effect of diet on a host and found that one kind of food was able to dramatically increase resistance to multiple stressors — like heat and free radicals — as well as to pathogens,” reported lead researcher Natasha Kirienko, who is an assistant professor of biosciences at Rice University in Houston.

By feeding C. elegans diets consisting of either the OP50 or HT115 strains of the bacteria E. coli, Dr Kirienko’s team found that E. Coli HT115, which provided vitamin B12, improved the worms’ survival after exposure to the bacteria Pseudomonas aeruginosa or Enterococcus faecalis OG1RF. It was determined that a lack of vitamin B12 lowers the worms’ ability to metabolize branched chain amino acids (BCAAs), resulting in an accumulation of partially metabolized BCAAs that damage the mitochondria of the cells. Conversely, increasing vitamin B12 availability improved mitochondrial homeostasis and resistance to infection.

“The key difference between the two diets is the ability of HT115 and OP50 to acquire B12 from the environment,” commented coauthor Alexey Revtovich, a research scientist. “We showed that HT115 is far more efficient at this.”

“Some labs use OP50 as their standard food, and others use HT115 or even another strain of E. coli,” observed coauthor Ryan Lee. “Our results show there are significant metabolic differences between these diets, and it’s likely those differences could contribute to substantial uncertainty in research outcomes.”

—D Dye

Dr Nath Talks on the ME/CFS NIH Intramural Study

Reprinted with the kind permission of Simmaron Research.

By Cort Johnson

It looked like we were going to be late … again. It was pouring cats and dogs as we eased the van around tangled web of streets that is the NIH campus scanning glumly at the rain-obscured buildings. Even our guide on the phone seemed to be lost.

It had been a wild 12 hours. The night before, reaching up to turn on the fan on my brother’s porch, I’d let loose a rather large bug which tumbled into my eye. Howling with pain I stumbled off to the bathroom where I managed to wash it out – leaving my eye reddened and swollen. The next morning, my eye still swollen, my partner insisted I see an eye doctor.

To our surprise we found somebody. The problem was was that his office was right in the heart of downtown Washington DC. – where parking is scarce and traffic cops take their jobs very seriously. Finding no parking we stopped in a loading zone across from the doctor’s office, hoping that the big yellow van with it’s solar panels, Nevada license plate and all would for the next 15 minutes be taken for a loading van –

After being assured the appointment would be short, I dashed inside where I was  bombarded by frantic calls from my partner (who does not drive the van). She had immediately been accosted by first one then another traffic cop.

After seeing the doctor who informed me (for $250 dollars) that insects in the eyes almost never cause problems (but who did give me drops) I dashed back out to the van to find my now none-too happy partner.

We sped off in the rain – still seemingly on time for the appointment with Dr. Nath. Hauling up to the NIH we tried no less than three entrances – only to be turned away at each them (our oversize vehicle thwarting one attempt) – and directed to the next. Finally, as our appointment time came and went, we found the right entrance – for, ironically, delivery vehicles.

After going through an extensive (and time-consuming) security check we headed off into the labyrinth that is the NIH clutching small hard to decipher maps and immediately got lost. The  minutes continued to tick by and rain strengthened into a deluge and eventually we managed to steer onto the right street. Our guide, still on the phone, told us to stop, we jumped out of the car and looked up, rain pouring down, at a steep, muddy climb.

Five minutes later – 45 minutes late for our hour appointment, we strode, soaked and bedraggled into Dr. Nath’s office. He immediately set us at ease, and with his next appointment running late stayed overtime with us. We were there to talk about the NIH Intramural ME/CFS study.

The NIH Intramural ME/CFS Study

Dr. Nath informed us that the applications to be in the NIH Intramural ME/CFS study have been gratifyingly robust.  Dr. Nath noted that it was entirely possible that this is the most rigorously examined patient group ever assembled for a study.

Then it was up to Canada, where he held a faculty position at the University of Manitoba (1990-97), and then he was at The University of Kentucky (1997-02). In 2002, he became Professor of Neurology and Director of the Division of Neuroimmunology and Neurological Infections at Johns Hopkins.Dr. Nath is leading the study. He has been around. He received his MD degree from Christian Medical College in India in 1981, completed a residency in Neurology from The University of Texas Health Science Center in Houston, did a fellowship in Multiple Sclerosis and Neurovirology at the same institution, and then another fellowship in Neuro-AIDS at NINDS.

in 2011, he became the Clinical Director of NINDS, the Director of the Translational Neuroscience Center, and Chief of the Section of Infections of the Nervous System. His research focuses on understanding the pathophysiology of nervous system infections and their outcomes, and the development of new diagnostic and therapeutic approaches for these diseases. He’s heavily involved in HIV research, the role endogenous retroviruses play in neurological diseases, and “undiagnosed neuroimmune and neuroinfectious diseases”.

He recently wrote a paper on Herpes Viruses, Alzheimer’s Disease, and Related Dementias: Unifying or Confusing Hypothesis?, which examined what role herpesviruses might be playing in dementia.

The NIH Intramural Chronic Fatigue Syndrome Study

The study takes place in two parts: a one week part which further assesses the potential participant and another one week section which measures a wide variety of parameters before and after an exercise test.

Requirements for entry are high, however, and not often met. You might say that many have been called – or rather have called – but few have been chosen. That was OK with Dr. Nath. “We need,” he explained, “to make sure that we’re studying the right population. That’s the best way to get to the answer, and then it’ll be broadly applicable.”

The response has been excellent.  Many people are traveling to participate, and they’re coming from all over. The NIH is even getting interest from people in other countries.

As of Dec. last year, 337 people had inquired about the study. One hundred and seventy-three were quickly screened out, and 164 participated in phone interviews. One hundred and twenty-seven made it to the medical record assessment stage.

Multiple reasons thwarted would-be participants from participating in the study.  The study required onset within 5 years which was triggered by infection. One-third had had the disease for too long, 20% had no evidence of infectious process (doctor’s records are required), 9% were too sick to travel, and just 3% were unwilling to have a lumbar puncture.

It is not an easy study! It’s a two-part, two-week plus study on a population, which studies suggest, has the lowest functionality of any disease. The study includes a lumbar puncture, a maximal exercise test, several nights in a metal box (metabolic chamber), tilt table test, muscle biopsy, brain scans, lengthy neuropsychological tests and scads of blood tests. Every part of you is going to be probed.The researchers were surprised at the last two figures. They expected, based on their experience from past studies, much higher percentages of people who were too sick to travel or unwilling to have a lumbar puncture. Dr. Nath well knows how difficult it can be to get people to participate in a study, but that’s not a problem here. Calling the numbers “very good”, Dr. Nath said the ME/CFS community was clearly “very motivated to participate in the study”.

Plus, you have to provide your entire medical history, get interviewed several times, and then, most likely travel.

Dr. Nath said he looked at the study – which is clearly larger and more intensive than most  – and said, “who is going to enroll in this study?” Laughing, he joked that, “I wouldn’t volunteer on my own study!” He was afraid no one was going to show up!  Instead he said the patients were very willing to undergo all the tests and are grateful for it.

Recruitment has been good, but as with any study, Dr. Nath said, it was high at first, and now it’s tailed off. As of March of this year, 19 ME/CFS patients and 21 healthy controls had completed the first phase of the study, and six people with ME/CFS and 7 controls had completed phase II.

Thus far, then, about half the projected participants (n=40 ME/CFS; 40 healthy controls) have gone through the first week of the study and about 15% have completed the entire study.

Quite a few people with autoimmune disorders have shown up during the filtering out process. Nath suggested that could be an interesting cohort to study on its own.  He’s also found quite a bit of head injury and loss of consciousness – which makes MRI and brain scans difficult to assess – and people with seizures and strokes. Interestingly, only one person had had a diagnosis of major depression….

High Percentage of Rare Diseases 

It’s a small sample set but it’s remarkable how many people participating in the first week were diagnosed with a rare disease. In something of a testament to the thoroughness of the study, almost third of week one participants (6/19) were found to have a rare disorder which the researchers believed was probably causing their symptoms and dismissed from the study. One appeared to have Parkinson’s Disease, another a neurological disease and I’m unsure of the others.

Big Data

They are gathering lots and lots of data – which brings its own problem. The study includes two different brain scans, blood, saliva, urine and stool samples, exercise data, tilt table data, spinal taps, Seahorse data, metabolic room data, cognitive testing, muscle and skin biopsies, and I’m probably missing some. I asked Nath, how will they able to integrate all this disparate data?

Nath agreed that it was a challenge, but noted that that kind of challenge is a pretty common challenge now. Some of the really big Alzheimer’s and Parkinson’s studies contain thousands of individuals, each of whom has done thousands of tests. Computational biology has become a major part of medical research.

Google, not surprisingly, is collaborating with the NIH to create better ways to analyze data. Many of the discoveries in medicine today, Nath said, actually occur as breakthroughs in physics; MRI and CT scans, for example – came from physics.

Their general hypothesis is that an infection triggers brain and immune system issues (ranging from persistent immune activation to immune dysregulation) that stay stuck.  They don’t believe the nature of the infection is particularly important.

No Preliminary Findings Yet

Nath was unable to give me any preliminary findings. One reason is that they are storing samples so they can run them all at the same time. Another is that, echoing Ron and Mark Davis’s thoughts, they don’t want to even try to come up with hypotheses yet. They simply want to gather more and more data.

Making a conclusion on the basis of small samples is, Nath said, the kiss the death. They will not even try to interpret their findings until about half the study is done.

If, when they get to the end of the study, they see trends but don’t quite have a significant result, they’ll do sample size calculations to determine how many more patients they’ll need to see to get to statistical significance. If the calculation says do another 10 patients, they’ll probably expand the study to do 12 more. If the calculation says do another 100 patients, that’s too much.

They’re preventing another kind of bias by recoding the samples, so the analyst doesn’t know which are from patients and which are from controls.

The Study

Brian Vastag’s visit raised the issue of mitochondrial problems. Nath believes studying the muscle itself may be more important than assessing mitochondrial problems using the blood, and added muscle biopsies to the study. The muscle biopsies will be tested for DNA analysis, structural issues, and staining for various kinds of cells.

The Open Medicine Foundation and Ron Davis apparently believe likewise. They’ve pumped a million dollars into an ME/CFS Collaborative Research Center at Harvard lead by Ron Tompkins which will focus on figuring out what is going on in the muscles.

Because lots of patients have autonomic symptoms, the NIH is doing tilt table tests. Once those turn out positive, Nath said, the next question is why the autonomic nervous system problems are present. They’re doing small fiber neuropathy skin tests and examining the heart, peripheral nerves, adrenal glands, and sympathetic nervous system functioning.

I asked him if there were any surprises, and there were.  As Robert’s story will show, the NIH doesn’t seem to be prepared for the level of devastation ME/CFS can wreak in a relatively young group of patients.

Nath said his personal contact with the patients has led him to develop a real appreciation for the disease. These patients, he said, “are devastated”. Whether or not this study finds a cause, the reality, Nath said, is that the lives of the study patients are “totally messed up.” Then he made an important point.  Seeing the patients in the flesh naturally causes him and other researchers to develop additional empathy for them and “another level of appreciation” for them and their disease.

It was clear that just by being there and exposing the researchers and doctors at the NIH to this disease, the participants in the study are making a difference.  The lengths to which some patients are going to participate in this study are amply illustrated by Robert’s story.

Participating in the Study

The NIH needs more participants. If you’re interested in helping to further ME/CFS research by participating in the study, check out the study criteria below.

All participants must be 18-60 years old and have at least a 7th grade education. People whose ME/CFS started after an episode of infection and who have severe symptoms lasting from 6 months to 5 years are eligible to participate in the study.

Find out more here.

Associations Between Autonomic and Orthostatic Self-report and Physician Ratings of Orthostatic Intolerance in Youth

Abstract

PURPOSE: There is no known biological marker or physical assessment to diagnose chronic fatigue syndrome (CFS), leaving physicians to heavily rely on self-report measures regarding the symptoms associated with CFS. Common symptoms of CFS include difficulty sleeping, joint pain, headaches, sore throat, cognitive dysfunction, physical exhaustion, dizziness, and nausea. Because of the overlap among CFS symptoms and autonomic functioning, we examined the association between 2 self-report measures of orthostatic and autonomic symptoms and a physician’s report of autonomic functioning (measures of changes in blood pressure and pulse) to further understand the association among autonomic functioning within individuals with symptoms of CFS.

METHODS: With data from an ongoing study, we used independent t tests and Pearson correlation tests to assess the association among the orthostatic domain from the DePaul Symptom Questionnaire, Autonomic Symptom Checklist composite scores, and the physician’s assessment of orthostatic intolerance obtained from a sample of 191 participants, 42 who were healthy controls.

FINDINGS: No significant demographic differences were found between the CFS-like group and the healthy controls. Results indicate a significant correlation between orthostatic and autonomic functioning (r = 0.58) and a correlation with a low effect size among autonomic functioning and physician measures of orthostatic functioning (r = -0.01 to 0.29). However, fewer correlations were found between self-reported symptoms of orthostatic functioning and the physician’s measures of orthostatic functioning.

IMPLICATIONS: These results suggest that although orthostatic dysfunction is reported in children and adolescents with CFS-like symptoms, the physical measures of autonomic functioning in this study were unable to detect these symptoms.

Copyright © 2019. Published by Elsevier Inc.

Source: Schultz KR, Katz BZ, Bockian NR, Jason LA. Associations Between Autonomic and Orthostatic Self-report and Physician Ratings of Orthostatic Intolerance in Youth. Clin Ther. 2019 Mar 12. pii: S0149-2918(19)30070-0. doi: 10.1016/j.clinthera.2019.02.010. [Epub ahead of print]

Pharmaceutical Interventions in Chronic Fatigue Syndrome: A Literature-based Commentary

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disorder characterized by prolonged periods of fatigue, chronic pain, depression, and a complex constellation of other symptoms. Currently, ME/CFS has no known cause, nor are the mechanisms of illness well understood. Therefore, with few exceptions, attempts to treat ME/CFS have been directed mainly toward symptom management.

These treatments include antivirals, pain relievers, antidepressants, and oncologic agents as well as other single-intervention treatments. Results of these trials have been largely inconclusive and, in some cases, contradictory. Contributing factors include a lack of well-designed and -executed studies and the highly heterogeneous nature of ME/CFS, which has made a single etiology difficult to define.

Because the majority of single-intervention treatments have shown little efficacy, it may instead be beneficial to explore broader-acting combination therapies in which a more focused precision-medicine approach is supported by a systems-level analysis of endocrine and immune co-regulation.

Copyright © 2019. Published by Elsevier Inc.

Source: Richman S, Morris MC, Broderick G, Craddock TJA, Klimas NG, Fletcher MA. Pharmaceutical Interventions in Chronic Fatigue Syndrome: A Literature-based Commentary. Clin Ther. 2019 Mar 11. pii: S0149-2918(19)30071-2. doi: 10.1016/j.clinthera.2019.02.011. [Epub ahead of print]

Diagnostic sensitivity of 2-day cardiopulmonary exercise testing in ME/CFS

Diagnostic sensitivity of 2-day cardiopulmonary exercise testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract

BACKGROUND: There are no known objective biomarkers to assist with the diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A small number of studies have shown that ME/CFS patients exhibit an earlier onset of ventilatory threshold (VT) on the second of two cardiopulmonary exercise tests (CPET) performed on consecutive days. However, cut-off values which could be used to differentiate between ME/CFS patients have not been established.

METHODS: 16 ME/CFS patients and 10 healthy controls underwent CPET on a cycle-ergometer on 2-consecutive days. Heart rate (HR), ventilation, ratings of perceived exertion (RPE) and work rate (WR) were assessed on both days.

RESULTS: WR at VT decreased from day 1 to day 2 and by a greater magnitude in ME/CFS patients (p < 0.01 group × time interaction). No interaction effects were found for any other parameters. ROC curve analysis of the percentage change in WR at VT revealed decreases of - 6.3% to - 9.8% provided optimal sensitivity and specificity respectively for distinguishing between patients with ME/CFS and controls.

CONCLUSION: The decrease in WR at VT of 6.3-9.8% on the 2nd day of consecutive-day CPET may represent an objective biomarker that can be used to assist with the diagnosis of ME/CFS.

Source: Nelson MJ, Buckley JD, Thomson RL, Clark D, Kwiatek R, Davison K. Diagnostic sensitivity of 2-day cardiopulmonary exercise testing in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. J Transl Med. 2019 Mar 14;17(1):80. doi: 10.1186/s12967-019-1836-0. (Full study)