Category Archives: stress

Long Haulers, Brain Fog and Post Exertional Malaise

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An excellent article recently published in the Atlantic was so well written that I have cut and pasted important snippets to help create this post. The review confirms many findings uncovered in my reading of several scientific publications.

You can read the full article here:

The crushing fog of long COVID

20 to 30 percent of patients report brain fog three months after their initial infection, as do 65 to 85 percent of the long-haulers who stay sick for much longer.

Of long COVID’s many possible symptoms, brain fog “is by far one of the most disabling and destructive,”

It is more profound than the clouded thinking that accompanies hangovers, stress, or fatigue.

It is not a mood disorder.

It is almost always a disorder of “executive function”—the set of mental abilities that includes:

  1. focusing attention,
  2. holding information in mind, and
  3. blocking out distractions.

Patients state they often lose focus mid-sentence.

Difficulty with simple tasks impairs activities of daily living.

“I couldn’t unload a dishwasher, because identifying an object, remembering where it should go, and putting it there was too complicated.”

The memories are there, but with impaired executive function, the brain neither chooses the important things to store nor retrieves that information efficiently.

Most people with brain fog are not so severely affected, and gradually improve with time. But even when people recover enough to work, they can struggle with minds that are less nimble than before.

“I’ve had surgeons who can’t go back to surgery, because they need their executive function,” Monica Verduzco-Gutierrez, a rehabilitation specialist at UT Health San Antonio.

That specific constellation of problems also befalls many people living with HIV, epileptics after seizures, cancer patients experiencing so-called chemo brain, and people with several complex chronic illnesses such as fibromyalgia.

It’s part of the diagnostic criteria for myalgic encephalomyelitis, also known as chronic fatigue syndrome, or ME/CFS

People with brain fog also excel at hiding it: to protect their jobs when still able to work, or to protect their reputation, or out of embarrassment.

“I know my value in many people’s eyes will be diminished by knowing that I have these cognitive challenges.”

Individuals with previously above average cognitive ability often test “normal” but suffer significant loss compared to their prior ability.

A team of British researchers analyzed data from the UK Biobank study. The findings revealed structural changes in the brain with loss of tissue on MRI scans that correlates with symptoms.

They found that even mild infections can slightly shrink the brain and reduce the thickness of its neuron-rich gray matter. At their worst, these changes were comparable to a decade of aging.

They were especially pronounced in areas such as the parahippocampal gyrus, which is important for encoding and retrieving memories, and the orbitofrontal cortex, which is important for executive function.

In most cases the virus probably harms the brain without directly infecting it.

Inflammatory chemicals can travel from the lungs to the brain, where they disrupt cells called microglia (immune cells in the brain).

In their presence, the hippocampus—a region crucial for memory—produces fewer fresh neurons, while many existing neurons lose their insulating coats (demyelination), so electric signals now course along these cells more slowly.

These are the same changes seen in cancer patients with “chemo fog”.

Neuro-inflammation is “probably the most common way” that COVID results in brain fog, but that there are likely many such routes, such as reactivation of dormant viruses such as Epstein-Barr virus, which has been linked to conditions including ME/CFS and multiple sclerosis.

By damaging blood vessels and filling them with small clots, COVID also throttles the brain’s blood supply, depriving this most energetically demanding of organs of oxygen and fuel.

These problems can be exacerbated or mitigated by factors such as sleep and rest, which explains why many people with brain fog have good days and bad days.

Although other respiratory viruses can wreak inflammatory havoc on the brain, SARS-CoV-2 does so more potently than influenza.

For adults following SARS CoV-2 infection:

risks of cognitive deficit (known as brain fog), dementia, psychotic disorders, and epilepsy or seizures were still increased at the end of the 2-year follow-up period.

For children following SARS CoV-2 infection:

in the 6 months after SARS-CoV-2 infection, children were not at an increased risk of mood (HR 1·02 [95% CI 0·94–1·10) or anxiety (1·00 [0·94–1·06]) disorders, but did have an increased risk of cognitive deficit, insomnia, intracranial haemorrhage, ischaemic stroke, nerve, nerve root, and plexus disorders, psychotic disorders, and epilepsy or seizures (HRs ranging from 1·20 [1·09–1·33] to 2·16 [1·46–3·19])….  Unlike adults, cognitive deficit in children had a finite risk horizon (75 days) and a finite time to equal incidence (491 days).

The fact that neurological and psychiatric outcomes were similar during the delta and omicron waves indicates that the burden on the health-care system might continue even with variants that are less severe in other respects.

There are no proven drug treatments for long-haulers.

But there is hope.

Cancer researchers have developed drugs that can calm inflamed microglia in mice and restore their cognitive abilities;

“Metformin can promote the regeneration of neural precursor cell populations and improve cognitive function in a preclinical model of cranial radiation and a pilot clinical study of children after cranial radiation and chemotherapy.”

Treating cancer therapy–related cognitive impairment | Nature Medicine

With regard to long-haulers, better sleep, healthy eating, and other generic lifestyle changes can make the condition more tolerable. Breathing and relaxation techniques can help people through bad flare-ups; speech therapy can help those with problems finding words.

“Some people spontaneously recover back to baseline,”

The largest group of long-haulers—those whose brain fog has improved but not vanished, can “maintain a relatively normal life, but only after making serious accommodations,”

Patients struggle to make peace with how much they’ve changed and the stigma associated with it, regardless of where they end up.

Post-exertional malaise—severe crashes in which all symptoms worsen after even minor physical or mental exertion is commonly reported.

Many long-haulers try to push themselves back to work and instead “push themselves into a crash,”

Post-exertional malaise is so common among long-haulers that “exercise as a treatment is inappropriate for people with long COVID,”

Even brain-training games—which have questionable value but are often mentioned as potential treatments for brain fog—must be very carefully rationed because mental exertion is physical exertion.

People with ME/CFS learned this lesson the hard way, and fought hard to get exercise therapy, once commonly prescribed for the condition, to be removed from official guidance in the U.S. and U.K.

In summary:

  1. Brain fog can occur even after mild or asymptomatic Covid-19.
  2. Although many patients improve over time, many are left with disability that can range from mild to incapacitating.
  3. Although these symptoms can occur following any viral infection, SARS CoV-2 seems to produce this with greater frequency compared to other viruses.
  4. Chronic brain inflammation is the likely cause in many individuals.
  5. Reactivation of Epstein Barr and/or other dormant viruses is suggested by various immune markers.
  6. The immune signature also suggests an immune response that mimics persistent infection in the absence of live SARS CoV-2 virus.
  7. Post exertional malaise following physical or mental exercise is a common and debilitating symptom without proven treatments. However there are guidelines that may help mitigate this devastating condition.
  8. Brain fog and post-exertional malaise are hallmarks of chronic fatigue syndrome/Myalgic encephalomyelitis which can occur following viral infections and major stress events such as physical and psychological trauma.
  9. Although not discussed in this post, chronically suppressed cortisol levels have been identified in this population. This in combination with physical changes noted on brain MRI demonstrate that there are physical correlates of brain fog.

In the meantime, preventive measures represent the low hanging fruit for health in general and with respect to the pandemic.

In the context of the COVID 19 pandemic I will close with the usual summary.

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. Follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels. Supplement with Vitamin D3 to get your levels above 30 ng/ml, >40ng/ml arguably better.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system
  8. Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)
  11. Drink water filtered through a high quality system that eliminates most environmental toxins.
  12. If you are eligible for vaccination, consider protecting yourself and your neighbor with a few jabs. Age > 50 and/or risk factors means clear benefit from a booster.

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

AHS 2022 Lecture, Acute and Long Covid, Nutritional and Lifestyle Immunology

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I recently gave a talk at the AHS 2022 meeting held at UCLA. You can view the video here:

This first slide gives a good overview.

The presentation covers a quick review of my presentations given last year at the PAH 2021 annual meeting (virtual) with additional information on long Covid.

Multiple nutrients acting synergistically support a balanced response to viral infections, including SARS CoV-2. Here is a picture.

The take home message is that no single nutritional intervention is likely to have significant impact with an acute infection unless all but one nutritional component is optimal. Nevertheless, there is compelling evidence that Vitamin D deficiency is rampant in the developed world and if one nutritional intervention is likely to be of benefit, Vitamin D supplementation, particularly in high risk populations, presents the most likely candidate. As usual, preventive supplementation would be preferable to rescue high dose intervention.

In a study of frail elderly hospitalized patients, regular vitamin D supplementation was associated with decreased mortality as demonstrated here. Compared to no supplementation, regular supplementation was associated with a 93% reduction in risk of death.

A study from Spain with very high dose Vitamin D in the form of Calcifediol showed significant benefit in hospitalized patients, suggesting that Vitamin D deficiency was prevalent in that population and that such a treatment intervention should be widely considered.

Calcifediol Treatment and COVID-19-Related Outcomes

Click to access dgab405.pdf

The following graphic from another nutrition review article, with red additions added by myself, demonstrates the complex interaction between nutrition and the two main components of our immune system, innate immunity (immediate response) and adaptive immunity (based on immune memory). Again red highlights added by yours truely.

And here is a slide from my lecture with quotes from that article.

Yet most Americans are deficient in many of these essential nutrients as depicted here. The percentages represent the % of Americans that fall below the estimated amount required to prevent deficiency in HALF of adults (a very low standard).

The EAR is a very low bar to meet, yet many Americans fall below even that low standard.

The SARS CoV2 virus interferes with a crucial component of the the initial (innate) immune response, the production of interferon 1 and the signaling of interferon one to immune cell mediators as depicted in this graphic.

SARS CoV2 on the left is compared to Virus X on the right. On the left interferon 1 (IFN) production and signaling is blocked by the virus, interfering with an effective and controlled immune response, on the right IFN is not blocked. A cascade of events results in TOO LITTLE, TOO LATE, AND THEN TOO MUCH of an immune response, producing a cytokine storm.

Obesity, insulin and leptin resistance, also interfere with the production and signaling of interferon. The result is that people with insulin and leptin resistance (pre-diabetes, Type 2 Diabetes as well as sarcopenia) experience a double hit. First the virus itself disrupts the immune response and superimposed upon the viral effect is the effect of insulin and leptin resistance on the immune response.

SOCS: suppressor of cytokine signaling. Several recent viral studies have shown that viral genes can hijack SOCS1 to inhibit host antiviral pathways, as a strategy to evade host immunity
On the left Interferon production and signaling are normal and a successful immune response is mounted. On the right the presence of insulin and leptin resistance, associated with obesity results in an initial inadequate response and a late excessive response. TOO LITTLE, TOO LATE, THEN TOO MUCH.

Factors that can quickly impact insulin and leptin resistance include all the components of an ancestral lifestyle depicted in my website graphic. A paleolithic or ancestral diet that eliminates sugar added foods and beverages, replacing those empty calories with nutrient dense foods, exercise, adequate restorative sleep, stress reduction, avoidance of environmental toxins, social connection. All of these affect health in general, mitigate insulin and leptin resistance, and support a balanced immune response to viral infection. The circle of health depicted below is surrounded by the many deleterious aspects of modern living. Thus, a mismatch between our evolutionary biology and present day life.

Here is a slide from my lecture that lists many lifestyle factors that can impact infection with any virus, including SARS CoV-2

My lecture also included discussion of Long COVID, theories of etiology and pathophysiology which will be discussed in my next post.

For the full lecture which is about 34 minutes long, please follow the link above.

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

Nutrition and Lifestyle vs Pandemic

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Earlier this year I gave 2 presentations on this topic at the (virtual) annual meeting of Physicians and Ancestral Health, a physician organization dedicated to incorporating evolutionary biology and lifestyle recommendations into the practice of medicine. Here is the first slide:

And here are some very important references:

Please note that this lecture was given before the delta variant arrived so the data applies to the pre-delta period.

MI= Myocardial Infarction (heart attack with loss of muscle), PE=Pulmonary Embolus, DVT= Blood Clots in legs, SIRS= Systemic Inflammatory Response Syndrome

I will skip several of the slides and get to the nutritional immunology and other lifestyle factors.

This slide shows many lifestyle factors that interact with the immune system. The “12% metabolic health” refers to a study demonstrating that only 12% of American adults are metabolically healthy, which will be explained later. Dysbiosis refers to an imbalance in gut bacteria favoring inflammation and immune compromise. The rest should be self explanatory but discussed in detail later in this series.

Here is the very busy slide that summarizes nutritional immunology:

w3/w6 refers to the omega 3 to omega 6 ratio in the diet, ROS= Reactive oxygen species (oxidative stress), CH: carbohydrates; GALT: gut-associated lymphoid
tissue; GPRs: G-protein-coupled receptors; FA: fatty acids; GI/GL: glycemic index/load; RAR/RXR:
retinoic acid receptor/retinoid X receptor; SCFA: short-chain fatty acids; TF: transcription factors; VDR:
vitamin D receptor.

Key points in this slide:

  1. Omega 3 fats from fatty fish fight inflammation, excess omega 6 fats from refined “vegetable oils” (corn, soy, cotton seed, sunflower seed, safflower, etc.) contribute to inflammation and blood clots, contributing to cytokine storm and bradykinin storm.
  2. Vitamin D interferes with the virus at multiple points.
  3. Adequate iron (Fe) from meat and seafood is essential for immune function (Iron from plant sources is much less bioavailable compared to meat and seafood.)
  4. Adequate complete protein (not available from vegan diets) is essential for immune function.
  5. Zinc and selenium (both found in seafood and meat) are essential for multiple protective pathways in the immune system (enhancing response to infection and mitigating excessive inflammatory response as cofactors for antioxidant enzymes)
  6. Sugar and high glycemic foods cause inflammation, high blood sugars suppress the immune system
  7. Dietary fiber supports a healthy gut microbiome which in turn suppresses inflammation and provides the gut lining with SFAs (gut epithelium requires SFAs for energy and function, gut barrier function needs SFAs)
  8. Phenolic compounds in colorful vegetables and berries modulate multiple essential immune pathways that can inhibit viral replication.
  9. Carotenoids, phenolics support several vital immune pathways.
  10. Omega 3 fats are the building blocks of chemicals that help resolve inflammation and mitigate against cytokine storm and bradykinin storm.
  11. Multiple vitamins and phenolics support our internal anti-oxidant system.
  12. To get a balanced protein intake we should eat “nose to tail”. Include connective tissue (home made bone broth is a great source) and organ meats (from grass fed/finished ruminants) in addition to muscle meat.

Here is another busy slide that presents more detail, note the reference at the bottom of the slide to read more.

Sorry for the small print but you can see the blow up on line by going here.

http://A Review of Micronutrients and the Immune System-Working …

So does the “Standard American Diet” meet these nutritional needs to support a healthy immune system?

The % above represent the % of American adults with intakes BELOW the EAR (Estimated Average Requirement) for various vitamins and minerals. But note the definition of EAR:

“nutrient intake value that is estimated to meet the requirement of half the healthy individuals to avoid symptoms of a clinical or subclinical deficiency” (NOT OPTIMAL LEVELS for immune function)


Note also that this study did not consider omega-3s, phytonutrients, flavonoids, polyphenols, fiber, etc., all of which are essential to a robust immune response to any virus including SARS CoV-2.

With regards to omega 3 vs omega 6 fats:

Omega 3 fats (EPA and DHA) found in seafood fights inflammation, blood clots. DHA and EPA are the building blocks of SPMs which help RESOLVE INFLAMMATION (MITIGATE CYTOKINE STORM)

We will return to this topic in my next post. We are just scratching the surface of a complex system.

In the context of the COVID 19 pandemic I will close with the usual summary.

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. Follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels. Supplement with Vitamin D3 to get your levels above 30 ng/ml. (read this Open Letter)
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system
  8. Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)
  11. If you are over age 12 and eligible for vaccination, consider protecting yourself and your neighbor with vaccination.

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

COVID 19 UPDATE: What have we learned?

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I was recently interviewed by a health blogger, Dmitri Konash, with specific questions about COVID 19. The podcast link is below.

Here are the questions and answer notes from the podcast.

QUESTION #1: It has been almost 4 months since Covid19 was declared a global pandemic. What are the main things which we have learned about the virus over these 4 months?

Very contagious, spread by droplet AND aerosol as well as fomites (CLOTHING, surfaces, pillows, blankets, etc). Aerosols are tiny particles suspended in the air for hours following a sneeze or cough or possibly yelling or singing. Droplets are larger particles that fall to the ground or onto surfaces. Depending on the surface the virus can remain infectious for up to 72 hours following droplet spread.

Individuals without symptoms can transmit disease (unlike most viruses) so this in combination with degree of contagion is very dangerous.

The average time from exposure to develop symptoms is 5 DAYS, 97.5% of people who develop symptoms do so within 11.5 days.

Some individuals never develop symptoms but can transmit disease for 2 or more weeks.

Infected individuals can carry the virus for up to 36 days (but we do not know how long an individual can transmit the disease) Average time to clear the virus is 14 days. (nasal PCR test)

Cough and sneeze can project 26 feet through the air, that is why masks can decrease risk but decreasing projection distance and viral load.

Masks Work, they decrease risk of disease transmission and probably decrease viral load, so if transmitted the recipient is probably less likely to develop severe complications (not proven but likely true).

Most infections are transmitted in closed spaces where many people are congregated and socializing such as parties, social gatherings, meetings, bars and restaurants.

Outdoor activity is safer.

The longer the contact between individuals the greater the risk.

The closer the contact the greater the risk.

Anyone can die from the virus but risk increases with age, diabetes, pre-diabetes, obesity, heart and lung disease, immune-compromise.

Any organ can be affected, lungs, brain, heart, kidneys, blood vessels.

Hyper-coaguable state can cause blood clots in the legs, lungs, heart and brain, any organ.

After recovering from infection individuals can suffer permanent damage to these organs.

We do not know how many people who recover will be immune or how long immunity could last. Already one case of re-infection has been reported.

The infection fatality rate (IFR) for COVID-19 IS 25 times greater than the H1N1 FLU pandemic.

A recent analysis comparing the 2009 H1N1 influenza A pandemic to COVID 19 suggested this:

 Case Fatality RateInfection Fatality Rate
2009 H1N1 Virus (flu)0.1% to 0.2%0.02%
COVID-19 New York8%0.50%
CFR is # deaths/#cases identified by nasal PCR, IFR is # deaths/actual # cases in a given population, estimated by antibody testing of a large population

For a discussion on the difference between CFR (case fatality rate) and IFR (infection fatality rate) see my previous post.

https://practical-evolutionary-health.com/2020/04/25/stanford-study-on-santa-clara-county-very-questionable-conclusions/

QUESTION #2: We reached the new high of newly diagnosed cases on June 28th. It looks like the virus is not subsiding. What is the status re drug and vaccine development?

Vaccine will likely take at least a year to develop, test, then manufacture and distribute.

Initially most vulnerable will probably take priority for vaccination. Massive vaccination will take longer.

THERE HAS NEVER BEEN A SUCCESSFUL CORONA VIRUS Vaccine. There are many corona viruses. They mutate quickly and a vaccine that works initially may become ineffective if/when new strains emerge.

Decadron (dexamethasone) IV decreases mortality rates in very sick patients.

Remdesivir shortens illness and might decrease mortality rate (the reduction compared to placebo fell short of statistical significance, p=0.059, cut-off for statistical significance is usually P=0.050)

Hydroxychloroquine and chloroquine have failed to show any benefit. A prevention trial remains underway.

There is no “cure”, just risk reduction.

QUESTION #3: What are the latest recommendations on prevention?

Social distance

Mask

Frequent hand washing

Get adequate sleep, sleep deprivation impairs immunity

Avoid alcohol which suppresses the immune system.

Get sunshine (vitamin D)

Develop a social “bubble”, limit contacts to close, reliable (responsible behavior) individuals

Exercise out of doors.

If overweight or obese, LOSE WEIGHT (Low Carb High Fat diet is MOST EFFECTIVE in combination with time restricted eating)

IF diabetes or pre-diabetes, carbohydrate restriction can rapidly achieve better blood sugar control, which is linked to risk reduction. Regular exercise can also improve insulin sensitivity, as can improved sleep habits.

QUESTION #4: There was some information recently about potential long-term impact on vital body organs for patients who had only mild symptoms. What actions do people who were tested positive for COVID19 should take to minimize long term impact to their health?

Follow general principles of healthy living (visit my website)

Sleep

Nutrition-anti-inflammatory diet

Exercise

Sunshine

Stress reduction

Social-community support

Minimize environmental toxin exposure (organic foods, safe personal and home-care products, visit EWG.org)

QUESTION #5: What actions should be taken by people who have been tested negative for COVID19 ? 

Same answer as question #4 above, lifestyle changes to enhance immune function and reduce systemic inflammation.

On July 10, a review article on COVID 19 was published in JAMA.

Pathophysiology, Transmission, Diagnosis, and Treatment
of Coronavirus Disease 2019 (COVID-19)

Here is the link.

https://jamanetwork.com/journals/jama/fullarticle/2768391

The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%

And here is a link to the JAMA patient information page for COVID 19.

https://jamanetwork.com/journals/jama/fullarticle/2768390

In the context of the COVID 19 pandemic I will close with the usual summary.

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. Follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system
  8. Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

Chronic Inflammation, the silent killer

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I was recently interviewed by a health blogger for his podcast. The topic was chronic inflammation. Here it is.

I prepared some notes for the interview. Here are the questions and answers.

What made you so interested in the topic of chronic inflammation?

Interest in chronic inflammation:

  • Emerging evidence, source of most chronic disease including mental health (depression, etc.) is inflammation
  • family health issues experience personally
  • health care policy interest since graduate school
  •  First started to question USDA dietary advice after reading GOOD CALORIES, BAD CALORIES, by Gary Taubes,
  • Experienced Statin myopathy, researched statin drugs, bad data, financial conflicts of interest. Sought alternative approaches to Coronary Artery Disease prevention.
  • In USA, Profit driven health care system evolved from more benign not-for-profit earlier system in medical insurance and hospital system. Drug and surgery oriented. Corporate ownership of multiple hospitals, concentration of wealth and power in the industry and in society in general
  • Saw this every day: growing obesity, Metabolic Syndrome, DMII, auto-immune disease. Root causes NOT ADDRESSED.
  • While recovering from surgery attended on line functional medicine conference on auto-immune disease, covering diet, sleep, exercise, sunshine, Vitamin D, environmental toxins, gut dysbiosis, intestinal permeability (THE GATEWAY TO AUTOIMMUNITY IS THROUGH THE GUT).
  • Introduced to EVOLUTIONARY BIOLOGY and Paleo Diet by my son

What diseases does chronic inflammation typically lead to? 

  • Cancer
  • Diabetes
  • Obesity epidemic, DIABESITY
  • Hypertension
  • Metabolic Syndrome (3/5: HTN, insulin resistance/high blood sugar, abdominal obesity, high TGs, low HDL),
  • Autoimmune diseases
  • Degenerative arthritis
  • Neurodegenerative disorders (dementia, Parkinson’s, neuropathy, multiple sclerosis)
  • Works of Dale Bredesen (dementia, “The End of Alzheimer’s”), Ron Perlmutter (Grain Brain), Terry Wahls (The Wahls protocol for MS), all FUNCTIONAL MEDICINE looking at root cause of illness, common-overlapping threads.
  • Interplay between sleep, circadian rhythm, exercise, sunlight, stress, environmental toxins, diet, processed foods, nutritional deficiency, gut microbiome, endocrine disruptors, intestinal permeability, oral and skin microbiome, social disruptors, GUT BRAIN AXIS. These are all part of one large ECOSYSTEM.
  • Positive and negative feedback systems requiring a SYSTEMS ENGINEERING approach to understanding root causes.
  • Butyrate is the preferred substrate for colonocytes, providing 60-70% of the energy requirements for colonic epithelial cells1,2. Butyrate suppresses colonic inflammation,3 is immunoregulatory in the gut,4 and improves gut barrier permeability by accelerating assembly of tight junction proteins.5,6
  • Improves insulin sensitivity, increase energy expenditure, reduce adiposity, increases satiety hormones,
  • HDAC activity inhibitor, PROTECTS GENES from removal of necessary acetyl groups.
  • Butyrate also influences the mucus layer. A healthy colonic epithelium is coated in a double layer of mucus. The thick, inner layer is dense and largely devoid of microbes, protecting the epithelium from contact with commensals and pathogens alike. The loose, outer layer of mucus is home to many bacteria, some of which feed on the glycoproteins of the outer mucus layer itself. Both of these mucus layers are organized by the MUC2 mucin protein, which is secreted by goblet cells in the epithelium. Supplementation of physiological concentrations of butyrate has been shown to increase MUC2 gene expression and MUC2 secretion in a human goblet cell line.7,8

What are the population groups which have higher risk of chronic inflammation? 

  • Obese
  • Sedentary
  • Poor-urban-polluted environment dwelling (air, water, noise, crowding, violence, racism, oppression)
  • Divergence from ancestral evolutionary biology
  • Working environment: indoors, polluted, oppressive supervisors, no sunlight, noise pollution, air pollution, toxic social situations, repetitive motion, bad ergonomics,
  • night shift, disruption of circadian rhythm
  • both parents working, no time for real food and family interaction, supervision of children.
  • screen time- sedentary behavior, lack of outdoor activity
  • Stress of social inequality, food insecurity, violent neighborhoods, nutritional deserts

What are the “danger signs” or typical symptoms which may signal a chronic inflammation? 

DANGER SIGNS:

  • Waistline (waist to height ratio, BMI)
  • Sarcopenia (muscle as an endocrine organ)
  • Sleep disturbance
  • Pain
  • Headaches
  • Depression
  • Lack of joy.
  • Brain fog, fatigue

What are the typical biomarkers of chronic inflammation?

  • METABOLIC SYNDROME (3 or more of the following: high blood pressure, elevated blood sugar, elevated Triglycerides, low HDL, obesity)
  • CRP predictive of cardiovascular events,
  • ESR associated with arthritis
  • Stress hormones (morning cortisol levels)
  • Resting Heart Rate and Heart Rate Variability

What are the typical sources of systemic chronic inflammation?

Sources of Chronic Inflammation:

Diet

  • N6/N3 FA ratio determined by too much Refined Easily Oxidized Vegetable Oils, not enough marine sources of N3 FA,  grain fed vs grass fed/finished ruminant meat. Loren Cordain research wild game FA composition = grass fed. Margarine vs Butter. Fried foods using Vegetable oils. Oxidized fats/oils, oxy-sterols in diet.
  • Sugar excess leading to insulin resistance
  • Refined carbs leading to insulin resistance (dense acellular….)
  • Disturbance of gut  microbiome from poor nutrition (sugar, refined carbs and vegetable oils all disrupt the microbiome)
  • Gut brain axis.
  • Food ADDITIVES AND PRESERVATIVES
  • Trans Fats (finally banned)

Endocrine disruptors/ BIOACCUMULATION

  • Plastics (microparticles in our fish, food and bottled water)
  • Plastic breakdown products
  • Phthalates added to plastics to increase flexibility ( also pill coatings, binders, dispersants, film formers, personal care products, perfumes, detergents, surfactants, packaging, children’s toys, shower curtains, floor tiles, vinyl upholstery, it is everywhere) 8.4 million tons of plasticizers produced annually. EWG.org
  • Pesticides, herbicides, glyphosate (Monsanto), DIRTY DOZEN, CLEAN FIFTEEN EWG.org
  • Medications
  • ABSORBED skin, eat, drink, breath,
  • BPS is as bad as the BPA it replaced
  • Polychlorinated biphenyls used in INDUSTRIAL COOLANTS AND LUBRICANTS
  • Flame retardants (PBDEs, polybrominated dipheyl ethers) are ubiquitous in furniture and children’s clothing. Also linked to autoimmune disease
  • Dioxins
  • PAHs (polycyclic aromatic hydrocarbons
  • Sunblock
  • CUMULATIVE BURDEN, INTERACTIONS, SYNERGY?

SLEEP DEPRIVATION CHRONIC IN OUR SOCIETY

Eating late vs time restricted eating

Gut Microbiome disrupted by

  • 1/3 of prescribed medications disrupt the microbiome AND increase intestinal permeability
  • Stress
  • Sleep deprivation
  • Sugar
  • Refined carbs
  • Refined veg oils
  • Over exercise and Under exercise, both are bad.
  • Environmental toxins

Gut dysbiosis and infections include (often chronic, low grade, not diagnosed)

  • Pathogenic bacteria, infection or overgrowth/imbalance
  • SIBO
  • Parasites
  • Viruses
  • BAD bugs > good bugs
  • Good bugs make vitamins and SCFAs required for colonocyte energy
  • Gut-Brain axis huge topic, VAGUS NERVE COMMUNICATION both ways, SCFA in gut and in CIRCULATION (butyrate, propionate, acetate), NEUROTRANSMITTER PRODUCTION (SEROTONIN, OTHERS), enterochromaffin cells producing > 30 peptides.
  • Overuse of antibiotics in medicine
  • AND use of antibiotics in raising our food.
  • Vaginal delivery vs C-section
  • Breast feeding vs bottle feeding

INCREASED INTESTINAL PERMEABILITY:

  • Caused by all factors above
  • Leads to higher levels of circulating LPS-endotoxin, bacterial products that create an immune-inflammatory response.
  • Incompletely digested proteins with AA sequences overlapping our own tissue causing autoimmunity/inflammation through molecular mimicry

Heavy Metal toxicity

  • Lead
  • Mercury
  • Cadmium
  • Arsenic

MOLD TOXICITY (> 400 identified mycotoxins, can cause dementia, asthma, allergies, auto-immunity)

  • At home
  • At work

What are the most efficient natural (non-medication) ways to address chronic inflammation?

  • Anti-inflammatory Diet, real whole food that our ancestors ate through evolutionary history (grass fed/finished ruminant meat, free range poultry, antibiotic free, and pesticide free food, wild seafood (low mercury varieties), organic vegetables and fruit, nuts, fermented foods, eggs)
  • Low mercury fish and seafood for omega three fatty acids
  • Sleep hygiene
  • Exercise, not too much, not too little, rest days, out of doors, resistance training, walking, yoga, Pilates, tai chi, chi gong, dancing, PLAYING!!!!!!!!!!!!!
  • Stress reduction: meditation, mindful living, forest bathing, sunlight, Playing, music, praying, SOCIAL CONNECTION, laughter, comedy, quit the toxic job, quit the toxic relationship, SAUNA/SWEAT, heat shock proteins, exercise
  • Vitamin D, sunshine, check levels
  • PLAY, PLAY, PLAY, LAUGH, DANCE, ENJOY, LOVE
  • Be aware of potential dangers of EMF, WiFi, hand held devices, blue tooth headphones.
  • Address environmental justice
  • Address social inequality, food insecurity
  • Tobacco addiction
  • Ethanol
  • Other substance abuse
  • Agricultural subsidies in US distort the food supply
  • Loss of soil threatens food supply
  • Suppression of science (global warming, environment, etc.,) worsens environmental degradation, creating an EXISTENTIAL THREAT.
  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. Follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system
  8. Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

COVID-19, Lifestyle interventions more effective than most drugs. (But Paxlovid is a winner)

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This discussion was originally posted before PAXLOVID WAS AVAILABLE. Paxlovid is very effective in reducing morbidity and mortality associated with Covid-19 infection. Standard dosing: PAXLOVID two 150-mg tablets of nirmatrelvir, one 100-mg tablet of ritonavir twice daily for 5 days.

Dose adjustments are necessary for certain medical conditions and there are many drug interactions that should be considered.

The results of a randomized placebo controlled clinical trial in high risk individuals has been published in the NEJM. The study was done just when Omicron hit. The study demonstrated an 89% reduction of hospitalizations and deaths by day 28 (absolute reduction of 6.2/100) with ZERO deaths in the Paxlovid group (7 in the placebo group). Paxlovid also had LESS side effects than placebo.

Another study from Israel demonstrated equally impressive results as shown here.

In addition, a study from the VA has looked at longer term effects (pre-print publication, still waiting for peer review.)

The study included 9000 Paxlovid patients treated within 5 days of symptom onset during the Omicron and subvariant waves and compared the treated patients with approximately 47,000 matched controls.

There was a 26% reduction in Long Covid.

Here is a breakdown of the Long Covid Symptoms

The VA study also showed a 48% reduction of death and 30% reduction in hospitalization after the acute phase (acute phase = first 30 days) as demonstrated here.

Many drug intervention trials for treating COVID-19 early in the pandemic have been disappointing. No studies have shown benefit for hydroxychloroquine, with or without azithromycin. This topic has been covered in previous posts. Remdesivir was FDA approved based upon one study that showed reduction in duration of symptoms. The mortality rate with Remdesivir, however, did not demonstrate a statistically significant difference when compared to “usual care”. https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19

Another study published in Lancet failed to show any clinical benefit from Remdesivir.

“No statistically significant benefits were observed for remdesivir treatment beyond those of standard of care treatment. Our trial did not attain the predetermined sample size because the outbreak of COVID-19 was brought under control in China. Future studies of remdesivir, including earlier treatment in patients with COVID-19 and higher-dose regimens or in combination with other antivirals or SARS-CoV-2 neutralising antibodies in those with severe COVID-19 are needed to better understand its potential effectiveness.”

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext

Likewise well designed studies of Ivermectin have shown no clinical benefit.

Monoclonal antibodies effective against early variants are no longer effective against the newer variants. So in terms of drug therapies for acute Covid infections we have Paxlovid for out patient care and dexamethasone for critically ill patients.

But we do know that certain underlying conditions such as obesity, diabetes, pre-diabetes (insulin resistance) and hypertension significantly increase risk of DEATH AND COMPLICATIONS with COVID-19. Since there are lifestyle interventions that can quickly and effectively mitigate these problems (diet, exercise, sleep, stress reduction….) now would seem like a good time to take our epidemics of obesity and diabetes in hand with aggressive lifestyle interventions to decrease the mortality rate of COVID-19 infection.

Such measures do not require expensive drugs or expensive drug trials, they simply require knowledge, guidelines and the will to implement change in our daily habits. Yet there has been little discussion about this in the media or on the part of public health officials.

Lets look at obesity in the US.

From 1999–2000 through 2017–2018, the age-adjusted prevalence of obesity increased from

30.5% to 42.4%, and the prevalence of severe obesity increased from 4.7% to 9.2%.

Click to access db360-h.pdf

The most effective tool for addressing obesity and diabetes is a very low carbohydrate diet.

Effects of the Low Carbohydrate, High Fat Diet on Glycemic Control and Body Weight in Patients With Type 2 Diabetes: Experience From a Community-Based Cohort

https://pubmed.ncbi.nlm.nih.gov/32193200/

This study was a done in a community-based program, not an academic practice setting. That is significant since it demonstrates feasibility outside of academic centers with standard community resources. The results of this study confirmed the results of many previous studies done in academic settings including better blood sugar control, reduction or elimination of diabetic medications, and significant weight loss.

“All patients following the LCHF diet who initially took
insulin had either a reduction or discontinuation of
this therapy by their healthcare provider when clinically
indicated, compared with less than a quarter of
those receiving usual care.“

In another study done in Italy, significant weight reduction (7 kg), waistline reduction (7 cm.), fat mass reduction (3.8%) and systolic blood pressure reduction (10.5 mmHg) were achieved in 3 months with a Very Low Carbohydrate diet.

Middle and Long-Term Impact of a Very Low-Carbohydrate Ketogenic Diet on Cardiometabolic Factors: A Multi-Center, Cross-Sectional, Clinical Study (https://pubmed.ncbi.nlm.nih.gov/25986079/

Nina Teicholz had an opinion piece published in the Wall Street Journal on May 30, discussing the USDA dietary guidelines that have largely ignored a massive body of evidence supporting a Very Low Carbohydrate Diet for obesity and diabetes. She cites many studies that have been ignored by the USDA dietary guidelines committee. Here is here opening statement.

“Americans with obesity, diabetes, heart disease and other diet-related diseases are about three times more likely to suffer worsened outcomes from Covid-19, including death. Had we flattened the still-rising curves of these conditions, it’s quite possible that our fight against the virus would today look very different.”

You can read the full article here:

https://www.wsj.com/articles/a-low-carb-strategy-for-fighting-the-pandemics-toll-11590811260

But think about that simple statement, THREE TIMES MORE LIKELY TO SUFFER WORSENED OUTCOMES FROM COVID-19. Yet these conditions are highly responsive to lifestyle interventions that not only mitigate obesity, insulin resistance and high blood pressure, but also enhance immune function.

More from Teicholz’s opinion piece:

“Other studies have found that dietary changes can rapidly and substantially improve cardiovascular risk factors, including conditions like hypertension that are major risk factors for worsened Covid-19 outcomes. A 2011 study in the journal Obesity on 300 clinic patients eating a very low-carbohydrate diet saw blood pressure quickly drop and remain low for years. And a 2014 trial on 148 subjects, funded by the National Institutes of Health, found a low-carb diet to be “more effective for weight loss and cardiovascular risk factor reduction” than a low-fat control diet at the end of the 1-year experiment.“

In a recent letter to the editor published in the journal METABOLISM, Dr. Casey Means points out:

A diagnosis of diabetes has been a key indicator of the severity of
COVID-19, and in this regard, the virus has relentlessly highlighted our
global Achilles heel of metabolic dysfunction, and points to a prime opportunity
to fight back.
That fight, however, is not going to be won with Clorox, Purell,
masks, or anti-IL-6 drugs. The fight will only be won through a serious
commitment to improving everyone’s foundational metabolic health,
starting with the lowest hanging evidence-based fruit: dietary and lifestyle
interventions.

Read the full letter here: https://www.metabolismjournal.com/article/S0026-0495(20)30118-9/pdf

In 2 pages the letter describes multiple benefits of better glucose control relative to COVID -19 infection and the immune system as well as reduction of factors that lead to cytokine storm (terminal event for many COVID-19 patients). The letter also discusses the benefit of reducing environmental toxins (discussed in previous posts about COVID-19 and other health problems) that would likely benefit COVID-19 patients.

Research published April 18th, 2020 found that patients exposed to
highest amount of environmental nitrogen dioxide (NO2) had increased
risk of death fromCOVID-19, and that long-term exposure to this pollutant
may be one of the most important contributors to fatality by
compounding lung inflammation [20].

Minimizing exposure to environmental
pollutants may serve a role in quelling the underlying pro-inflammatory
state that characterizes metabolic disease and COVID-19 associated
cytokine storms.

Other environmental toxins, including persistent organic pollutants
(POPs) found in air, water, and food generated from pesticides
and industrial chemicals, are also strongly implicated in the pathogenesis
of metabolic syndrome; promoting “clean living,” toxin-avoidant
strategies for patients as simple as emphasizing organic foods, home
air purification, and non-toxic home supplies could be considered, although
the clinical utility of these measures in the acute setting is unknown
[21].

In discussing the white elephant in the room he states:

What is starkly missing is the clear, simple, and strong recommendation for no added
sugar or ultra-refined carbohydrates, both of which are known drivers
of postprandial hyperglycemia and inflammation. As a medical community, we must not miss the opportunity to serve patients with straightforward, evidence-based nutritional and lifestyle strategies to assist in glycemic control.

I would encourage you to follow the link and read the 2 pages supported by multiple peer-reviewed references.

An ancestral (paleo) diet is also very effective for addressing insulin resistance, diabetes type 2 and obesity. Multiple studies have demonstrated this. Although an ancestral approach is typically low carb it is not typically ketogenic, but a ketogenic ancestral diet (high in non starchy vegetables to support the gut microbiome) can be implemented by restricting fruits to one serving of berries per day and limiting starchy vegetables.

Even without severe carbohydrate restriction, an ancestral anti-inflammatory diet will quickly address insulin resistance, type 2 diabetes, and obesity. In this insulin resistance was reversed in 10 days.

And another study:

And another study

And here is a slide from one of my lectures with references on how an ancestral diet modulates immunity.

Leptin resistance, insulin resistance and obesity travel together. Here is yet another study demonstrating the effectiveness of an ancestral diet.

If you have obesity, diabetes or pre-diabetes the Very Low Carbohydrate version of the anti-inflammatory diet linked above would be the fastest and most effective intervention you can immediately employ to reduce your risk of succumbing to COVID-19. (Of course wear an N-95, follow good hygiene with hand-washing frequently, and use a HEPA filter or Corsi-Rosenthal box in your home, office, and enclosed work spaces)

In the context of the COVID 19 pandemic I will close with the usual summary.

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. Follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels. Supplement with Vitamin D3 to get your levels above 30 ng/ml, >40ng/ml arguably better.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system
  8. Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)
  11. Drink water filtered through a high quality system that eliminates most environmental toxins.
  12. HEPA filters or the home-made version (Corsi-Rosenthal box) used in your home or workplace can reduce circulating viral load as discussed on this website.
  13. If you are eligible for vaccination, consider protecting yourself and your neighbor with a few jabs. Age > 50 and/or risk factors (Diabetes, pre-diabetes, insulin resistance, hypertension, obesity, heart disease, COPD, asthma, cancer treatment, immune suppression) suggests benefit from a booster. Risk for complications of boosters in adolescents, especially males, without risk factors, may equal benefit. Previous infection with Covid can be considered as protective as a booster. Discuss risk vs benefits with your doctor.

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

COVID-19 Sweden vs Other Countries

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5/21/2020 deaths/ million 7 day running average doubling time
cumulative deaths/million/day days
SWEDEN 379 3.3 46
Norway 43.6 0.13 241
Finland 54.9 0.52 138
Denmark 95.6 0.49 120
USA 282 4.02 49
NZ 4.3 0 598
stay home test-trace leadership
isolate example
SWEDEN no yes ?
Norway yes yes good
Finland yes yes good
Denmark yes yes good
USA late/variable POOR poor
New Zealand yes excellent excellent

Sweden was a source of controversy for the choice against instituting a stay-home policy. As you compare Sweden with other Scandinavian countries above you will see a dramatic difference in deaths per million (cumulative), running 7 day average deaths per million per day, and doubling time. The higher the doubling time (in days) the more a country has slowed the spread. New Zealand is the obvious winner. Early and aggressive action, effective test/trace/isolate, excellent leadership and example by the president are the hallmarks of success in New Zealand. Of course New Zealand is a small island with minimal international business and tourism so the comparison is not fair. HOWEVER, their success and strategy are obvious.

The US failed (and continues to fail) on test/trace/isolate despite the bluster and misrepresentations from the Whitehouse. California and Washington instituted early measures with respect to stay-home but without adequate test kits all of US states have been unable to execute the test/trace/isolate strategy proven effective in other countries. President Trump promised California 100,000 nasal swabs per week three weeks ago. They have not arrived. (California Department of Public Health)

Thus comparing USA to Sweden we see that with adequate social distancing, test/trace/isolate, Sweden did almost as well (or as poorly) as the US where stay at home was employed on a variable time line and to different degrees between the states.

You can review worldwide data, download spreadsheets, choose countries for comparison here.

Test/Trace/Isolate + Social distance + Masks4all + cooperation = SUCCESS

Had the US responded early and effectively, stay-home could have ended very quickly and safely with much less economic disruption.

Poor Management = inadequate Test/Trace/Isolate and other measures.

The New England Journal of Medicine published an article discussing the failure of the
USA relative to Test/Trace/Isolate.

Failing the Test — The Tragic Data Gap Undermining the U.S. Pandemic Response

 

The importance of  Reviving the US CDC after annual cuts by the Trump Administration is discussed here.

On March 25 the NEJM published an editorial on responding to the pandemic.

We did not follow the recommendations.

The AMERICAN ENTERPRISE INSTITUTE, a conservative think-tank, published a comprehensive Roadmap to Reopening.

Unfortunately we have not followed that roadmap.

So boost your immune system and meet the challenge with your personal behavior. Be smart.

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. You must follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system
  8. Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

 

COVID-19: ARDS, CYTOKINE STORM, and GLUTATHIONE

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My good friend Dr. Deborah Gordon recently sent me a terrific article on an Integrative Medicine Approach to Covid-19. It confirmed much of what I have discussed about COVID-19 and provides 383 scientific references (many of which were cited in my previous posts). Thank you Dr. Deborah!

In my last post I promised to write about glutathione and cytokine storm.

Cytokines are proteins made by our immune system. When our body suffers an infection, cytokines act as essential signaling proteins that produce a defensive inflammatory response. In a cytokine storm the usual regulatory process that helps resolve inflammation becomes disturbed and self destruction can occur.

With COVID-19 this can happen in any organ of the body but frequently starts in the lungs, resulting in ARDS (Acute Respiratory Distress Syndrome).

In most clinical contexts the mortality rate of ARDS is 40-45%. In the context of COVID-19 it is 80-90 % lethal in most clinical reports (twice the usual mortality rate for ARDS). However, the ICU doctors in the Northwell Hospital system in NYC have been using NAC (n-Acetylcysteine).

While using NAC as part of their treatment protocol of COVID-19 associated ARDS, they are getting 50% of patients off the ventilator with a significant reduction in mortality rates compared to previous reports (personal communication with a Northwell physician and also mentioned in the Review Article cited above.)

This drug (also available as a dietary supplement) has been used for decades to treat acetaminophen (APAP) overdose (Tylenol brand name, also called paracetamol in Europe). If not treated early APAP overdose commonly causes death from liver failure.

Chronic acetaminophen toxicity is the most common cause of liver failure leading to liver transplant in the US.

How does this treatment  with NAC work in the setting of APAP overdose?

“When paracetamol is taken in large quantities, a minor metabolite called N-acetyl-p-benzoquinone imine (NAPQI) accumulates within the body. It is normally conjugated by glutathione, but when taken in excess, the body’s glutathione reserves are not sufficient to deactivate the toxic NAPQI. This metabolite is then free to react with key hepatic enzymes, thereby damaging liver cells. This may lead to severe liver damage and even death by acute liver failure.”

NAC (n-acetylcysteine) provides cysteine, one of the three amino acids that make up glutathione.

“glutathione synthesis is primarily controlled by the cellular level of the amino acid cysteine, the availability of which is the rate-limiting step.”

So by providing a source of cysteine, the body produces more glutathione which can detoxify the liver damaging metabolites of APAP.

Glutathione is our MASTER ANTI-OXIDANT. Since a cytokine storm involves an overwhelming amount of oxidative stress, glutathione is obviously important.

Clinical research in the 1990s established that the lungs of patients with ARDS are very deficient in glutathione.

A profound 20 fold reduction was confirmed in this study.

“Glutathione is a tripeptide that is able to react with and effectively neutralize oxidants, such as hydrogen peroxide. The present study found that the alveolar epithelial lining fluid of patients with ARDS was deficient in total glutathione compared with that of normal subjects (31.5 ± 8.4 versus 651.0 ± 103.1 µM, p = 0.0001) and patients with cardiogenic pulmonary edema (31.5 ± 8.4 versus 154.1 ± 52.4 µM, p = 0.001). In addition, a greater percentage of total glutathione was in the oxidized form in patients with ARDS compared with normal subjects (30.6 ± 6.1 versus 6.4 ± 2.9%, p = 0.03). This deficiency of reduced glutathione in the alveolar fluid may predispose these patients to enhanced lung cell injury.

Subsequent studies of humans with ARDS on ventilators showed clinical benefit by increasing glutathione levels with NAC.

“In our controlled clinical trials with NAC we found that patients with ARDS have depressed plasma and red cell glutathione concentrations, that these levels are substantially increased by therapy with intravenous NAC and there are measurable clinical responses to treatment with regard to increased oxygen delivery, improved lung compliance and resolution of pulmonary edema.”

Despite these findings decades ago, the use of NAC for ARDS has not been widely adopted. But it would make sense to employ this inexpensive medication, widely used for APAP overdose, for ARDS and in particular for cytokine storm caused by COVID-19.

Oxidative stress decreases glutathione levels and if these levels reach a critically  low level in tissues, organ damage can ensue rapidly. Cytokine storm is the extreme example.

Chronic alcohol abuse also decreases protective glutathione levels in the lung.

In my recent posts on COVID-19 I have pointed out that alcohol (even 2 drinks) suppresses the immune system for at least a few days. Alcohol consumption is a double hit, first as an immune suppressant, then as a major source of oxidative stress and reduction in protective glutathione levels. Two glasses of wine tonight followed by a COVID-19 sneeze in your face the next day could be the difference between an effective immune response (mild symptoms) versus an overwhelming life threatening infection!

Likewise, one night of inadequate sleep (which immediately suppresses immunity) followed by a COVID sneeze in your face the next day could have the same deleterious effect.

Below is a chart from the review article mentioned at the start of this post. Notice the top line states “ADDRESS SLEEP, STRESS, DIET, SUGAR, ALCOHOL”

If you have been reading my posts on COVID-19, you have heard this before.

integrative medicine chart

Notice the second row in the chart with escalating doses of NAC as intensity of disease increases. When cytokine storm hits NAC dose recommendations peak and glutathione (available for IV administration) is recommended. IV glutathione surprisingly is not part of most hospital formularies and I have never seen it used in a hospital setting. Functional medicine physicians sometimes use it outside of the hospital setting. IV glutathione has become a sexy and lucrative office procedure in some functional medicine practices.

NAC has high bioavailability, meaning it is absorbed well in our gut. So oral supplementation can rapidly and effectively increase levels of glutathione in the body. IN FACT, treatment of acetaminophen overdose in the ER typically begins with oral NAC (often administered through a naso-gastric feeding tube, passed through the nose and into the stomach) Doses are often calculated by the regional poison control center (available by phone 24/7/365) and subsequent doses follow a standard protocol based on weight.

I would encourage you to read through this COVID-19 INTEGRATIVE MEDICINE review article.

It is thick with science but you might be surprised by how much you understand and learn.

In the chart above there is specific mention of Vitamin C supplementation in escalating doses as degree of illness increases. Vitamin C is an important anti-oxidant and in that sense is a glutathione sparing agent helping to mitigate glutathione depletion.

Other important factors mentioned in the article and the chart above include items mentioned here in previous posts: ZINC, ZINC IONOPHORES, phytochemicals (quercitin, EGCg, curcumin), Vitamin D, exercise, sleep, stress reduction, sunshine.

So I will close this post the way I have closed on many posts related to COVID-19.

Support your immune system.

In the context of the COVID 19 pandemic I will close with the usual summary.

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. Follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels. Supplement with Vitamin D3 to get your levels above 30 ng/ml, >40ng/ml arguably better.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system
  8. Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)
  11. Drink water filtered through a high quality system that eliminates most environmental toxins.
  12. HEPA filters or the home-made version (Corsi-Rosenthal box) used in your home or workplace can reduce circulating viral load by 80%. This works for any respiratory virus transmitted by aerosol and this winter we have the triple threat of RSV, Influenza, and SARS-CoV-2. It also decreases indoor air pollution.
  13. If you are eligible for vaccination, consider protecting yourself and your neighbor with a few jabs. Age > 50 and/or risk factors (Diabetes, pre-diabetes, insulin resistance, hypertension, obesity, heart disease, COPD, asthma, cancer treatment, immune suppression) suggests benefit from a booster. Risk for complications of boosters in adolescents, especially males, without risk factors, may equal benefit. Previous infection with Covid can be considered as protective as a booster. Discuss risk vs benefits with your doctor.

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

Glutathione review links are below:

Glutathione!

Mitochondrial Glutathione, a key survival antioxidant

Glutathione: overview of its protective roles, measurement, and biosynthesis

Study shows only 12% of US adults are metabolically healthy!

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What does this mean? The authors of this study looked at several important markers of health: waist circumference, fasting blood sugar, hemoglobin A1c, blood pressure, triglycerides, HDL, and whether someone was taking any medication related to these markers. They used data from the National Health and Nutrition Examination Survey 2009-2016. Only 12.3% of US adults qualified as healthy on all measures. So how did we get into this horrible situation?

Let’s step back and look at modifiable factors that play into these health measures.

  • Adequate restorative sleep
  • Stress
  • Nutrition
  • Exercise
  • Sunlight (Vitamin D)
  • Social connection
  • Environmental toxins
  • Rest

I have discussed the importance of sleep in several posts. Following this link you will find recommendations for good sleep habits that can enhance the quality and duration of your sleep.

If you have not watched Dan Pardi’s discussion of “HOW TO OPTIMIZE LIGHT FOR HEALTH” I recommend you watch this.

STRESS

Stress reduction is a huge topic. Managing stress involves so many areas it deserves a separate discussion. But here are some basics. Getting adequate sleep is the place to start. Activities like Meditation, Yoga, moderate exercise (walking outdoors in a green space) Tai Chi, music, practicing Mindfulness, and spending time with family and friends are all potential avenues to reduce the deletrious effects of stress in our lives.

NUTRITION

I have presented one approach to an anti-inflammatory diet  and if you have not read through the details just follow the link. The low hanging fruit begins with elimination of processed foods, sweetened beverages, and pro-inflammatory “vegetable oils” (OILS made from corn, soy, cottonseed, safflower, sunflower, canola, margarine). EAT WHOLE FOODS.

TO LEARN ABOUT THE ILL-EFFECTS OF “VEGETABLE OILS” LISTEN TO NINA:

EXERCISE

My post about exercise as medicine can be found here. 

The best way to exercise is to play as described by my friend Daryl Edwards in his TED talk.

 

Most Americans do not get enough, but some get too much. Moderation is important.

SUNLIGHT

Getting outdoor light exposure early in the day and avoiding the deleterious effects of artificial light in the evening (wear blue light blocking glasses in the evening) are two important ways to get the most benefit from light exposure, improve your sleep and enhance your Vitamin D level. Exercise outdoors in a green space provides more benefit than walking the treadmill indoors.

SOCIAL CONNECTION

Blue Zones are areas in the world that have the greatest numbers of individuals living to age 100. The climates and food varies among the various areas. They  all have two things in common. First is a high degree of social connection, strong family ties, lifelong friends. Social connection within a supportive community is arguably one of the most important factors affecting health, longevity, and healthspan. Second, they eat REAL WHOLE FOOD.

blue zones longevity hotspots.jpg

 

ENVIORNMENTAL TOXINS

Part of eliminating environmental toxins includes consuming organic fruits and vegetables and eating meat, poultry and eggs from hormone-free, antibiotic-free, free- range/pastured sources. (ALL PART OF AN ANCESTRAL/PALEO DIET) If you are not familiar with the “dirty dozen” and the “clean 15” head on over to EWG.org where you will learn not only about what foods have the most/least residual pesticides, but also what personal care products and household cleaners are safe for you and your family.

WATER: Because humans have spent the last 4-5 decades polluting our air and water there is probably no water supply that is totally free of enviornmental toxins. To minimize your consumption of enviornmental toxins, filter your drinking water through a high quality system.

REST

Matthew Redlund MD has written a great book “THE POWER OF REST”. Here he discusses why sleep is not enough.

The fact that only 12% of American adults are metabolically healthy should be cause for great alarm. All chronic and degenerative  diseases including dementia, heart disease, stroke, arthritis and cancer rise as metabolic health deteriorates.

Remember, this website offers educational information only. Consult your health care provider for medical advice.

Sleep well, exercise outdoors, laugh, love, engage in meaningful work, drink filtered water, eat clean, eat whole foods, get plenty of sunshine, spend time with those you love.

Doctor Bob

 

My Autoimmune Disease: remission with the AIP (and one medication)

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In September of 2018 I awakened with swollen, red and painful hands. I could not make a fist. I could not grip a steering wheel without extreme pain. I left dropped items on the floor because it was too painful to pick them up. All of my joints were painful and stiff. My legs were swollen. My wife had to help dress me so I could go to work. The simplest hand techniques to perform nerve blocks were painful. Just putting on sterile gloves caused severe pain. This happened just a few days after a week of camping. I felt weak all over and had trouble sleeping, unable to find a comfortable position.

(My camping vacation included digressions from my typical paleo/ancestral diet. I drank wine, ate some gluten containing foods and some dairy. I ate some wheat and sugar containing deserts.)

As a physician I ordered a variety of blood tests for tick born illness (such as Lyme’s Disease), rheumatoid arthritis, and other disorders that could cause my symptoms. All tests were negative except for an inflammatory marker (hsCRP) which was very high.

I queried physician friends about something I may have overlooked. No suggestions were forthcoming above and beyond what I had already done.

I prescribed myself a non-steroidal anti-inflammatory drug  NSAID. That provided modest relief but I was still suffering severe symptoms.

After 6 stubborn weeks I consulted a rheumatologist and he diagnosed me as having  “sero-negative” rheumatoid arthritis. Given the choice of several pharmaceutical interventions I chose the least toxic and started a drug called hydroxychloroquine. I was told it would take about 3 months to produce results, and in the meantime should continue the NSAID.

I immediately started to follow the Autoimmune Protocol AIP

Within one week of the AIP the redness in the joints of my hands was gone.

Within 2 weeks the pain in my joints was significantly reduced.

Within 3 weeks the swelling in my hands/fingers was completely gone and I stopped the NSAID. I no longer had pain in my hands and fingers while doing every day tasks.

Within 4 weeks I was able to resume my daily yoga and Pilates routine.

Within six weeks I felt in complete remission.

My rheumatologist agreed that I appeared to be in remission at follow up visit (no signs of inflammation, synovitis, etc., on examination with resolution of presenting symptoms) but he was and remains skeptical about the auto-immune protocol.

My clinical response was clearly way ahead of the expected time sequence for hydroxychloroquine. I concluded that the AIP was a major factor in my recovery.

All X-rays and MRI scans of my joints (which have suffered from osteoarthritis) were negative for the typical findings associated with rheumatoid arthritis.

The autoimmune protocol is a combination of lifestyle modifications involving diet, sleep, exercise, and stress reduction. It goes beyond the paleo diet. The paleo (ancestral) diet  eliminates processed/refined foods,  grains, legumes, dairy, added sugar, and refined vegetable oils. It stresses the consumption of a variety of organic vegetables and organic fruit, grass-fed meats, organ meats, free range poultry and eggs, wild seafood. The auto-immune protocol adds further restrictions: no nuts, eggs, nightshades, seeds, spices from seeds, and absolutely no alcohol.

There are many reasons for the added restrictions under the AIP. The added dietary restrictions are important for what they avoid but also important for the resulting increase in other beneficial foods that are allowed. The foods are omitted because they can cause or contribute to: gut irritation, dysbiosis, act as carrier molecules across the gut barrier, increase gut permeability, and/or cause inflammation. In theory, by eliminating those foods (hopefully on a temporary basis) and substituting nutrient dense less potentially harmful foods, we reduce some of the contributing factors to autoimmunity and inflammation.

For a detailed discussion of the AIP I suggest you visit Sarah Ballantyne’s  website and read her book: The Paleo Approach, Reverse Autoimmune disease and Heal Your Body.

Avoiding potentially harmful foods and beverages while increasing healthy nutrient dense foods represents the major focus of many individuals following the AIP. But equally important are the other lifestyle components. These include obtaining adequate  restorative sleep, reducing/managing stress (Stress Reduction and Health), getting reasonable amounts of playful exercise (this should be fun and occur in a green space as much as possible), sunshine, eliminating exposure to  environmental toxins, drinking filtered water, and frequent contact with supportive family and friends. Without addressing all of these areas one is not likely to succeed in achieving remission from an auto-immune disease.

In addition to Sarah’s Ballantyne’s book and website, if you have an auto-immune disease I recommend Dr. Terry Wahl’s website and book. Dr. Wahl’s, a medical school faculty physician, teacher and researcher,  was wheelchair bound with Multiple Sclerosis and facing death having failed all available medical treatments as well as some experimental drug protocols. She read about functional medicine, paleo nutrition and evolutionary biology in order to create her own treatment plan. One year latter she was in remission and riding her bike 20 miles. She subsequently raised money to do clinical research using her version of the AIP and has published a successful clinical trial.

There have been few controlled clinical trials of the AIP for auto-immune disease, largely because it does not involve drug research (no profits to be made) and because the NIH does not like to fund studies that alter multiple parameters at one time. Unfortunately, NIH funding has followed a drug and surgery model of medical treatment and does not look favorably on lifestyle interventions (one exception being the Mediterranean diet). I hope that bias changes in the future. In the meantime, physicians and scientists like Terry Wahls MD and Dale Bredesen MD, PhD (neurologist/researcher/author, The End of Alzheimer’s) remain pioneers in functional medicine and lifestyle interventions, being left to start their own foundations and raise money to fund medical research.

Both of these physicians have conducted clinical trials of lifestyle interventions (see below) that have produced revolutionary results, largely ignored by major medical societies and medical organizations. Progress occurs slowly, today’s iconoclasts are often tomorrows Nobel laureates.

Sometimes, despite significant clinical improvement with the AIP, some medication remains necessary with an auto-immune disease. If the auto-immune disease has been present for a long time, permanent damage may be present. That does not represent failure. If one can reduce drug doses, eliminate one or more drugs from a complicated medical regimen, and improve symptoms beyond what drugs alone achieve, I would call that success. Anecdotal reports from many patients (including my own) with auto-immune disease, suggest that it is not a cure-all, and those that show significant clinical improvement demonstrate various time responses ranging from weeks to several months in order to see results. But there are no down-sides to the AIP, no bad side-effects, no dangerous drugs, and only potential for clinical improvement. That seems like a no-brainer to me.

After eight weeks of strict dietary adherence, having achieved remission and appearing to be stable, I slowly added back small amounts of eggs, nuts and some nightshades (one at a time, observing for negative responses). I have been successful with that approach. I have not suffered any symptoms of rheumatoid arthritis since my initial remission. I remain on a paleo/ancestral diet and remain very cautions with regards to sleep habits, exercise, stress reduction, and social support. I try to laugh frequently and continue to engage in meaningful work. All of these components are essential to the AIP and to healthy living in general.

The following are links to published studies on the auto-immune protocol as well as links to a similar lifestyle intervention for Alzheimer’s disease. Another link is an editorial on inflammatory bowel disease and diet. The Autoimmune Protocol has been studied for Inflammatory Bowel Disease. In a peer reviewed published clinical trial it improved symptoms and inflammation seen on endoscopy, even producing remission in some patients. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647120/) It has also been studied for Hashimoto’s Thyroiditis and found to be effective .(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592837/)

Efficacy of the Autoimmune Protocol for Hashimoto’s Thyroiditis

Efficacy of the Autoimmune Protocol for Inflammatory Bowel Disease

Randomized control trial evaluation of a modified Paleolithic dietary intervention in the treatment of relapsing-remitting multiple sclerosis: a pilot study.

Multimodal intervention improves fatigue and quality of life in subjects with progressive multiple sclerosis: a pilot study.

Diet and Inflammatory Bowel Disease

A Multimodal, Nonpharmacologic Intervention Improves Mood and Cognitive Function in People with Multiple Sclerosis.

Reversal of cognitive decline in Alzheimer’s disease.

Inhalational Alzheimer’s disease: an unrecognized – and treatable – epidemic.

A colleague and scientist (Pedro Bastos), after reading my post, sent the following links to related articles (two by Loren Cordain, and a Master’s Thesis by one of his graduate students). For those interested in understanding the theories of molecular mimicry as triggers and mechanisms in autoimmune disease, Cordain’s work is outstanding.

Cereal grains, double-edged sword, Loren Cordain, 1999, Evolutionary Aspects of Nutrition and Health.

Rheumatoid Arthritis, molecular mimicry, dietary lectins, Loren Cordain, 2000, British Journal of Nutrition

Master’s Thesis, auto-immune disease and Paleo Diet, Trevor Connor

Eat clean, sleep well, exercise out-doors, get sunshine, love and laugh.

Bob Hansen MD