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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 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

Sleep! You can’t live without it.

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Circadian rhythm refers to the cycling of hormones according to the time of day. Every hormone cycles with daylight and darkness, each in it’s own way. Our brain has a master clock, called the circadian clock, controlled by specialized cells deep in the brain. There is a direct connection from our retina (in the back of the eyes) to the circadian clock in the brain. Blue light (part of the normal outdoor spectrum of light) stimulates very specific receptor cells in the retina which in turn communicates directly with the circadian clock telling the brain whether it is day or night. To synchronize our hormones and achieve restorative sleep, we must get outdoor light exposure to our eyes (without sunglasses, early in the day) and limit light exposure in the evening.

Artificial light, especially from cell phones and other devices that emit intense blue light, shift work, late night social activity, poor eating habits, sedentary lifestyle and at the opposite extreme, late evening workouts,  can all disrupt our circadian rhythm preventing adequate restorative sleep. A rare genetic illness called fatal insomnia that strikes adults at middle age prevents sleep and results in death within a few months, highlighting the importance of sleep. Sleep deprivation can kill a human quicker than starvation! Adequate amounts of deep non-REM sleep are required for tissue regeneration, healing, DNA repair and immune function. REM sleep with dreaming provides great benefit by organizing our memory, discharging the emotional content of traumatic events, and facilitating creative brain activity. One night of short-sleep produces a state of inattention and slow reflexes as dangerous as driving under the influence of alcohol intoxication. Chronic  short sleep and disrupted circadian rhythm results in increased risk of depression, cancer, hypertension, diabetes, dementia, obesity, metabolic syndrome, insulin resistance, heart attack and stroke, to name a few. Sleep interruption immediately halts weight loss during a calorie restricted diet (likely the result of hormonal disruption). So getting an adequate amount of restorative sleep every night is essential to good health. Here a few tips to help achieve a good night’s sleep each and every night.

  1. GET OUTDOOR LIGHT EXPOSURE ON YOUR EYES WITHOUT SUNGLASSES EVERY DAY, EARLY IN THE DAY. This helps set your biologic/circadian clock. Even on a cloudy day, outdoor light is much stronger and natural than indoor light. It is essential for setting your biologic/circadian clock. If you cannot get outside, stand or sit in front of a large window for 20-30 minutes in the morning, looking outside. Take a lunch break outside without sunglasses. Wear a shade hat instead of sunglasses. Your brain needs to experience natural outdoor light during the day.
  2. Avoid bright light in the evening, especially the light from TV, computer screens, cell phones, which all emit intense blue light and trick your brain into thinking it is daytime. Wear blue light blocking glasses/goggles for 2-3 hours before bed. (Amber tinted glasses which block blue light can be purchased on-line and can be worn over reading glasses) There is also software available that will decrease the blue light intensity of computer screens and cell phones in the evening.
  3. Practice time restricted eating. Limit all eating to an eight hour period, thus providing for an over-night fast of 16 hours. If that does not seem possible try to limit eating to a 10-hour period which provides a 14-hour overnight fast. This improves sleep, circadian rhythm, blood pressure, blood sugar and reduces stress hormones. NO SNACKS BETWEEN MEALS. NO FOOD FOR 2 HOURS BEFORE BED. For every hour decrease in eating time period from 12 hours to 8 hours you get health benefit.
  4. Eat an anti-inflammatory diet.
  5. If you snore, are overweight/obese, fall asleep during the day, or do not feel refreshed in the morning ask your doctor to order a sleep study. Obstructive Sleep Apnea makes restorative sleep impossible and increases risk of heart attack, stroke and most chronic diseases.
  6. Avoid alcohol altogether and avoid caffeine after late morning.  Alcohol in the evening may help you fall asleep but it results in a withdrawal from alcohol during the night. This disrupts normal sleep patterns.
  7. Sleep in a cold, dark, quiet room. Use black-out curtains, no night lights, no phone charger lights, no lights of any kind should be on in the room. Any amount of light in the room impairs the production of melatonin which facilitates sleep onset.
  8. Have a wind–down time every evening. Develop habits of non-stressful activities, soft music, dim light, casual conversation, enjoyable reading. Do not spend evening time dealing with finances, conflict, or emotional activity.
  9. Try a magnesium supplement before bedtime. Magnesium glycinate, magnesium citrate, magnesium gluconate, are absorbed much better than cheaper supplements such as magnesium oxide. Magnesium L-Threonate is expensive, but it crosses the blood brain barrier into the brain with the greatest brain penetration of all magnesium supplements.
  10. Manage stress with yoga, meditation, regular exercise (but no intense exercise in the evening.) Perform most of your exercise outdoors in a green space. This provides much more health benefit than the equivalent exercise indoors.
  11. Regular contact with supportive family and friends is essential to health and reduces stress. The greatest predictor of health vs disease is the amount of social connectedness an individual experiences.
  12. Establish regular wake-up times and go-to-bed times. Regular sleep habits are essential. If you must rely on alarm clocks you do not have good sleep habits.

A few words about alcohol, caffeine and sleeping pills.

A drink or two in the evening may help you relax but it disrupts your sleep by causing a mild episode of alcohol withdrawal as your liver metabolizes the alcohol and your blood levels drop. Even this slight degree of alcohol withdrawal will impair a good night’s sleep.

Caffeine impairs sleep by blocking adenosine receptors in the brain. Adenosine is the neurotransmitter that increases gradually during the day creating a sate referred to as sleep pressure. Some people metabolize caffeine quickly, others slowly. The slower you metabolize caffeine the longer it takes to clear it from your adenosine receptors. Without adequate sleep pressure (adenosine receptors filled with adenosine in the brain) you cannot fall asleep. Many sleep experts recommend complete abstinence from caffeine and suggest that if you need caffeine to get started in the morning you are regularly sleep deprived.

Sleeping pills of all kinds interfere with normal sleep architecture. While they facilitate falling asleep, they impair your ability to achieve deep restorative stages of sleep and can produce many undesirable side effects including addiction, withdrawal symptoms, sleep walking, sleep driving, worsening of asthma and COPD, constipation, diarrhea, daytime drowsiness, burning and tingling sensations, unusual dreams, weakness, heartburn, etc…. Most importantly they all interfere with cycling through the various stages of sleep in a normal, restorative pattern!

If you want to explore these concepts in depth here are two excellent books that discuss sleep and circadian rhythm.

Why We Sleep, by Matthew Walker Ph.D.

The Circadian Code, by Satchin Panda Ph.D.

Eat clean, sleep well, spend time exercising out of doors, love one another.

Bob Hansen MD

A Paleo physician’s journey through major surgery

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At age 46 I had a total hip arthroplasty (THA). Metal and plastic components replaced my hip joint (the stem, ball and socket of the hip). I am convinced that if I had adopted a Paleo lifestyle at age twenty instead of age 58 I would have not needed that surgery. But more about that another time.

On Monday I underwent a revision of that surgery to replace some components, scrape out bad bone, remove inflamed joint lining, flush out plastic debris, and place some bone grafts into areas where bone cysts had formed. The surgery was necessary because the plastic debris from my first artificial joint had stimulated my immune system in a way that caused my macrophages (white blood cells) and osteoclasts (a special kind of bone cell) to start destroying the bone around my hip socket. This process is called osteolysis.

Our immune cells evolved to destroy and consume bacteria and viruses, not plastic powder. So as the plastic liner of my hip prosthesis wore down, the plastic debris provided a constant source of inflammation, stimulating my immune system to get rid of a foreign invader. The bone around my prosthesis got caught in friendly fire. This problem does not seem to occur since a newer form of plastic, having only 10% the wear rate of the old plastic has been introduced. Time will tell if that proves to be true.

To prepare for surgery I reviewed my Paleo behavior with respect to diet, sleep, exercise, stress reduction and outdoor time. My exercise routine was already very reasonable. I had been strictly avoiding grains (except for occasional white rice) and legumes but did include some fermented dairy (kefir and cheese) and wine. So I eliminated all dairy and all alcohol. Sleep has always been an issue because as a physician I take call and sometimes work through the night with emergency cases.

My last call night was 3 weeks before surgery and I was up all night. The next day I flew to NJ for two important events (a reunion and a wedding) both of which were definitely not Paleo environments. A flight cancelation required more sleep deprivation in order to reach my first event on time. That sleep deprivation in combination with the changes in time zone disrupted my circadian rhythm so upon returning home two weeks before surgery I knew I had to play catch-up to be ready for surgery. I avoided alcohol except for a few drinks at my brother’s wedding and violated the wheat prohibition once with a piece of wedding cake.

When I returned to California I was 6 pounds heavier and jet lagged. I promptly got an upper respiratory infection (probably acquired on my flight home) which started in my throat and nose and went to my lungs.

So now I am jet-lagged and infected just two weeks from surgery. Not a good situation.

Thereafter I was strictly Paleo in diet, sleep, and stress reduction (yoga and meditation) but had to limit exercise to yoga and walking in order to fight the infection and prepare for surgery. I spent as much time walking outdoors as was feasible and focused on eight hours sleep each night. After one week I was beating the URI so I decided to do two 30 minute sessions of resistance training during the last week before surgery.

By the day of surgery the URI was completely cleared and I was down 6 pounds to my baseline.

I self administered my own pre-operative medication protocol (designed to mitigate post operative pain) and received a spinal anesthetic from my friend and colleague using a combination of local anesthetic and a small dose of spinal morphine. The latter can provide pain reduction for up to 24 hours after surgery.

So here is the amazing result.

5 hours after surgery I walked without pain using a walker bearing full weight on the surgical leg. I walked again that evening without pain. I knew this was the honeymoon period because the spinal morphine was still protecting me.

The next morning the honeymoon was over but I was still able to walk with full weight bearing without any pain medications and subsequently walked several times up and down the hospital halls during the first three post operative days. Although I had pain with movement I had no pain at rest.

On the day after surgery my CRP (C reactive protein) was 0.2 mg/dl. CRP is a measure of inflammation in the body. Normal range is zero to 0.5. I was elated. One day after a major traumatic event which typically initiates an inflammatory cascade, I did not have excess inflammation throughout my body as measured by CRP. My WBC (white blood cell count) was also normal.

A paleo lifestyle will not prevent pain after surgery but being in a low inflammatory state before surgery certainly helped with recovery.

My walking ability immediately after surgery and during the next three days astounded the physical therapists and nurses. They all stated I had set records.

My colleagues in the Anesthesia Department could not believe that I received no opiate or NSAID pain medications during my recovery. It is now five days since surgery. I have taken no opiate pain killers or NSAIDs except for low dose aspirin (starting yesterday) to help prevent blood clots

I avoided NSAIDs because NSAIDs increase intestinal permeability (which leads to an inflammatory response) and also because NSAIDs increase risk of cardiovascular events (heart attack, stroke, blood clots in the legs which can travel to the lungs and cause death in severe cases)

I can attribute my success to many factors including an excellent anesthetic, a great surgeon, an optimal pre-operative medication protocol, the superb nursing and therapy staffs and the Paleo lifestyle. In preparing for surgery I was able to make an effective come back from a stressful travel week, two successive nights of sleep deprivation and an upper respiratory infection only because of the Paleo approach.

As I walked my laps around the orthopedic unit I noticed that most patients spent the entire day in bed except for a few laps each day with PT. Many factors contribute to that problem. Our PT department is very aggressive but post operative pain, obesity, inflammatory diets and sedentary lifestyles all contribute to slow recovery. The hospital menu is highly inflammatory thick with processed-carbohydrates, pro-inflammatory grains, legumes, and refined vegetable oils, and yes,  even some trans fats. A strictly Paleo menu would be very helpful. But most of those patients have been living the Standard American Lifestyle (inflammatory diet, chronic sleep deprivation, inadequate exercise, poor stress management, etc.)  for a lifetime prior to surgery and it can take months to years of a Paleo lifestyle to mitigate a lifetime of self abuse. Even then some damage is permanent (like my hip).

I ate the hospital’s fresh fruit, vegetables and wild seafood, the rest was delivered from home by my loving spouse. Kathie is my anchor in the storm and my guiding light when I become lost. The importance of love and human physical contact is well recognized by the Paleo community so it is appropriate that I end with an expression of gratitude to Kathie and the host of friends who visited me during recovery. Hugs and kisses are as important as an anti-inflammatory diet.

Live clean and prosper.

Bob Hansen MD

The bacteria in your gut are essential to your health Part II, obesity, metabolic syndrome and dysbiosis

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I have discussed the evidence linking the mix of bacteria in your gut (gut flora) to health and disease in Part I. The Bacteria in your Gut are essential to your health Part I | Practical Evolutionary Health

Today I will discuss the evidence related specifically to  obesity and metabolic syndrome (the constellation of obesity, insulin resistance, high blood pressure, and abnormal blood lipids). My discussion will follow closely the evidence and theory presented in research and review papers authored by Dr. Cani and colleagues. The first one is titled:

“Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics.”

You can find the full text of this article here .

I have had the pleasure of corresponding with Dr. Cani by e-mail regarding her many publications investigating the relationship between gut flora, obesity, and metabolic syndrome.

“Recently, we and others have identified several mechanisms linking the gut microbiota with the development of obesity and associated disorders (e.g. insulin resistance, type 2 diabetes, hepatic steatosis).”

Explanation: The gut microbiota are the bacteria, viruses and other “bugs” that reside in our intestines. Insulin resistance can occur in various parts of the body, wherever insulin has an effect including fat cells, liver, muscle, brain. When higher amounts of insulin are required to achieve an effect this is called insulin resistance. In Type 2 diabetes, the pancreas is still able to make insulin but insulin is less effective in controlling blood sugar. In Type I diabetes the pancreas no longer produces insulin. Hepatic Steatosis means fatty liver disease. The liver accumulates fat and this can lead to cirrhosis, liver failure and death. Alcohol consumption can cause this but when alcohol is not involved this is called Non-Alcoholic-Fatty-Liver Disease (NAFLD). Our nation presently has an epidemic of not just obesity but also NAFLD. Evidence points to  excess carbohydrate consumption and excess consumption of vegetable oils (linoleic acid)  as contributing factors in NAFLD.  Carbohydrate restriction and consumption of saturated fat, particularly medium chain fats (as found in coconut) can protect against NAFLD. But the gut flora also play a role. The mechanisms involved are many.

“Among these, we described the concept of metabolic endotoxaemia (increase in plasma lipopolysaccharide levels) as one of the triggering factors leading to the development of metabolic inflammation and insulin resistance.”

Endotoxemia occurs when a toxin from certain kinds of bacteria circulates in the blood. This endotoxin enters our blood through our intestines under conditions in which the protective barrier of the intestines is compromised. The compromise of the intestinal barrier is variously referred to as ” leaky gut” or “increased intestinal permeability”. Wheat gluten-gliadin  causes increased intestinal permeability (especially in celiac disease) as can other plant lectins. In this discussion, the gut bacteria also contribute in the setting of “dysbiosis” (the beneficial effects of helpful bacteria are overwhelmed by the harm-causing bacteria when a healthy balance is not present)

Lipopolysaccharide (LPS) comes from the outer wall membrane of certain bacteria. Blood plasma is the liquid part of blood in which the blood cells circulate. So an “increase in plasma lipopolysaccharide” simply means that there is more LPS circulating in the blood. That is a bad thing. Depending on how much is circulating this alone can cause organ failure and death and is a major part of the physiologic changes involved in septic shock. But lower levels of LPS circulating in the blood can cause chronic low grade inflammation and insulin resistance. Obesity is associated with chronic inflammation and increased LPS circulating in the blood and being distributed to various organs where it wreaks havoc.

“Growing evidence suggests that gut microbes contribute to the onset of low-grade inflammation characterizing these metabolic disorders via mechanisms associated with gut barrier dysfunctions.”

“We have demonstrated that enteroendocrine cells (producing glucagon-like peptide-1, peptide YY and glucagon-like peptide-2) and the endocannabinoid system control gut permeability and metabolic endotoxaemia.”

That is a mouth-full. Over thirty different kinds of hormone producing cells have been found in the human intestine. These cells are called enteroendocrine cells. The hormones produced by these cells have many effects. You can find a great review of these cells and their effects here .

In Dr. Cani’s review article she describes how some of these hormones produced in the gut can increase intestinal permeability and allow more of the toxic, inflammation producing LPS to enter the bloodstream. But these hormonal effects are just part of the picture. Another part relates to endocannabinoids.

The  Endocannabinoid system in humans is complex and relates to hunger, satiety, energy metabolism, and yes gut permeability. Endocannabinoid refers to our internal (endo) production of cannabis like substances. Pot smoking people get the munchies because of the appetite stimulating effects of marijuana. But endocannabinoids have many other physiologic effects including the modulation of pain, mood, immune function and memory.

Dr. Cani describes in great detail the evidence supporting the roles that the gut flora play in influencing intestinal permeability mediated through the effects of various hormones and endocannabinoids. In animal and human studies changing the gut flora produces changes in these hormones and endocannabinoids which in turn can increase or decrease intestinal permeability and increase or decrease circulating LPS.

It turns out that specific  Prebiotics can produce growth of beneficial gut bacteria and through the series of steps outlined above, reduce inflammation in the body, improve blood sugar, improve insulin sensitivity, and decrease fat,

Oh, and similar to the endocannabinoid system, there is an “apelinergic system” in our bodies that also plays a role. If you want to read more about these systems you should read the original article and the other links below to related articles.

I have discussed in the past that fecal transplants have been used to treat the specific dysbiosis that occurs with C Difficile colitis. But fecal transplants have many potential beneficial uses.

The Fatlose 2 trial is presently studying the effects of fecal transplants on insulin resistance and related problems in human volunteers. I will let you know when the results are published, Studies conducted in rodents have demonstrated significant weight loss and improved insulin sensitivity when obese rodents receive fecal transplants from lean rodents.

In summary: dysbiosis represents an unhealthy mix of bacteria in the gut

  • dysbiosis causes increased intestinal permeability (leaky gut)
  • increased intestinal permeability leads to increased circulating LPS, which is bad
  • elevated levels of circulating LPS create a chronic state of inflammation which contributes to obesity and metabolic syndrome
  • the mechanisms that link dysbiosis to intestinal permeability include hormonal disruption (enteroendocrine cells) and the endocannabinoid system. Other mechanisms are also likely in play.
  • prebiotics and probiotics can mitigate dysbiosis, reduce intestinal permeability, reduce inflammation, and offer potential therapy for obesity and metabolic syndrome
  • fecal transplantation offers a potential for treatment for obesity and metabolic syndrome, research is underway

Our ancestors lived and evolved for a few million years prior to the relatively brief ten thousand years of agriculture and one hundred years of industrialization. The overuse of antibiotics in medicine and animal husbandry have contributed to dysbiosis. Other factors include stress, disruption of circadian rhythm, sleep deprivation. Cesarean delivery and avoidance of breast feeding conspire to dysbiosis. Processed foods feed unfriendly bacteria in our guts at the expense of beneficial bugs. Agricultural foods have introduced dietary lectins which also increase intestinal permeability and thereby contribute to chronic inflammation. The further we stray from our evolutionary niche, the more problems we experience.

This discussion just touches the surface of gut flora, dysbiosis, health and disease. We have yet to explore the gut-brain axis. Our gut and microflora communicate with and effect the function of our brain and other organs as well.

We will continue to explore health and disease from an evolutionary perspective.

Below are links to articles related to our discussion.

Peace, health and happiness.

BOB

Gut microbiota controls adipose tissue expans… [Benef Microbes. 2014] – PubMed – NCBI

Glucose metabolism: Focus on gut microbiota, … [Diabetes Metab. 2014] – PubMed – NCBI

Probiotics, prebiotics, and the host microb… [Ann N Y Acad Sci. 2013] – PubMed – NCBI

Crosstalk between the gut microbiota a… [Clin Microbiol Infect. 2012] – PubMed – NCBI

Gut microbiota and its possible relationship … [Mayo Clin Proc. 2008] – PubMed – NCBI

Enteroendocrine Cells: Neglected Players in Gastrointestinal Disorders?

Intestinal Permeability, Food and Disease

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In medical school I learned some fundamental concepts about nutrition and digestion that turn out to be wrong. For example, we were taught that proteins in our diet are completely broken down into single amino acids in the gut, then absorbed through the wall of the intestine as individual amino acids. Turns out that not all proteins are completely digested in this manner and that fragments of proteins that are several amino acids long can be absorbed through the gut and enter our blood. Examples of such proteins include wheat gluten and bovine serum albumin (found in cows milk and whey protein) to name a few. The problem with absorbing such nutrients into our bloodstream is that these protein fragments are “foreign” and can be recognized by our immune systems as foreign, triggering an immune (inflammatory) response.

Some peptides (short chains of amino acids) in bovine serum albumin have structural similarity to peptides in human tissues. This foreign protein has been implicated in autoimmune diseases such as Multiple Sclerosis, Rheumatoid Arthritis and Type 1 Diabetes.

Other substances such as bacterial endotoxin similarly can be absorbed into the blood and cause trouble. Endotoxin, also called LPS or  Lipopolysaccharide, is a major component of the outer membranes of certain kinds of bacteria (gram negative bacteria such as E-coli) that live in the  Lumen of our gut. High levels of endotoxin circulating in the blood occur during septicemia and can result in death from septic shock. Lower levels of circulating endotoxin have been demonstrated to contribute to alcoholic and non-alcoholic liver disease, both of which can cause liver failure and death.

Intestinal wall permeability is governed by many factors. There are regulatory proteins that open and close the gaps (tight junctions) between the cells that line the walls of our intestines, thereby allowing more and larger foreign substances to enter our blood. This mode of entry is referred to as “paracellular” since it does not involve the usual absorption mechanism through the walls of the cells that line the intestines.

Substances regularly consumed by Americans known to increase intestinal permeability include gluten (the sticky protein found in wheat, barely, rye, oats), alcohol, non-steroidal anti-inflammatory drugs  like ibuprofen (Motrin, Advil), naprosyn (Alleve), and aspirin.  Refined “vegetable oils” that are high in a specific Polyunsaturated fatty acid called linoleic acid (examples of these vegetable oils include corn oil, soy oil, cottonseed oil) have also been demonstrated to increase intestinal permeability.

Vegetable oils have also been found to enhance the liver inflammation and destruction caused by  alcohol which is at least in part mediated by absorption of endotoxin and ultimately also caused by oxidative stress.

The same applies to non-alcoholic liver fatty liver disease. (Progression of alcoholic and non-al… [Drug Metab Pharmacokinet. 2011] – PubMed – NCBI)

Interestingly, consumption of saturated fat (as found in beef tallow, coconut oil, butter and cocoa butter-the oil of dark chocolate) protects the liver from inflammation and destruction caused by alcohol, while polyunsaturated fat consumption (vegetable oils)  do the opposite. (References above and below)

There is growing evidence for a link between auto-immune disease and Alterations in intestinal permeability. Increased intestinal permeability (IP) has been observed in a substantial percentage of individuals with Type I diabetes. It is commonly observed in populations at high risk of developing Crohn’s disease and has been observed in patients who subsequently develop Crohn’s disease. Patients with ankylosing spondylitis have increased IP and although these patients are typically treated with NSAIDs which increase IP, the effects of NSAIDS have been isolated from a primary defect in IP which is shared by relatives without the disease.

“increased intestinal permeability is observed in association with several autoimmune diseases. It is observed prior to disease and appears to be involved in disease pathogenesis.”

A paleolithic diet avoids all sources of gluten (paleo is grain-free) and it also avoids refined “vegetable oils”. These food items present a double hit relative to inflammation. First, they increase IP which increases circulating levels of various “foreign” proteins and other foreign macromolecules which can stimulate the immune system. The second hit from these food items represents their direct inflammatory effects once absorbed into the body. I have previously discussed the  inflammatory response to excess omega six fats here.

An excellent review of the importance of the ratio of omega six fats found in “vegetable oil”  to omega three fats found in fish oil can also be found here ,  here   and  here.

The potential inflammatory response and anti-nutrient effects of cereal grains and in particular the gliadin portion of wheat gluten has been discussed and reviewed in multiple papers including:

Do dietary lectins cause disease?

Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders

BMC Medicine | Full text | Spectrum of gluten-related disorders: consensus on new nomenclature and classification

BMC Medicine | Abstract | Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity

Bioactive antinutritional peptides derived from cere… [Nahrung. 1999] – PubMed – NCBI

Antinutritive effects of wheat-germ agglutinin and… [Br J Nutr. 1993] – PubMed – NCBI

This discussion just scratches the surface of the effects of intestinal permeability and health. Future discussion will address how the micro-flora (bacteria and viruses that live in our GI system) affect intestinal permeability, our brains, our immune system and our health.

Avoiding foods that we have not evolved to eat will result in decreased inflammation and will often reduce the symptoms of auto-immune and other inflammatory diseases. Many present day diseases are considered by evolutionary biologists to represent a mismatch between our culture, food, and our evolutionary biochemistry. These diseases were likely rare or non-existent  before the advent of agriculture and the subsequent industrialization of society with highly processed foods.

Eat only pastured meat, free range poultry and eggs, wild seafood, fresh vegetables, fruit and nuts and you will avoid the problems discussed above as well as a host of other problems to be discussed in future posts.

Peace,

Bob Hansen MD