Category Archives: congestive heart failure

COVID-19: ARDS, CYTOKINE STORM, and GLUTATHIONE

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.

  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, sugar increases inflammation, contributes to metabolic dysfunction and impairs immunity.

In a future post I will describe my PERSONAL approach to dietary supplements in the context of COVID-19. I will also discuss the issue of an ADVANCED DIRECTIVE, in case you are hospitalized.

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

 

 

 

Paleolithic Diet Reversed Osteoporosis and Fatty Liver in an 82 year old man

Joe (not his real name) is an 82 year old man who presented to me in 2009 with severe degenerative arthritis of the spine, debilitating chronic pain,  osteoporosis, coronary artery disease, congestive heart failure and fatty liver. When I first met him in 2009 he weighed 265 pounds (6 foot), had just undergone multi-vessel coronary artery bypass surgery. He could not walk more than 30 feet without feeling short of breath and severe low back pain. He was referred to me for interventional pain management. At that time the only way he could sleep was in a hospital bed with his head elevated to a 90 degree angle. Otherwise he experienced “orthopnea” (shortness of breath lying flat caused by congestive heart failure). His osteoporosis (demineralization of bone) was so bad it was difficult to do pain blocks using X-RAY because the bone did not show up well on X-Ray due to the osteoporosis. He had also suffered compression fractures in the lumbar spine. Compression fractures are caused by weak bones where just the weight of the body can cause one or more vertebrae to partially collapse.

I recommended a paleolithic-carbohydrate restricted diet. He lost 90 pounds and on the paleo diet was able to get off some of his medication for congestive heart failure.

I saw Joe yesterday for an interventional pain management procedure (radio-frequency ablation of nerves to his painful arthritic lower lumbar facet joints). He gets these about every 6 months to treat chronic pain.

I recalled the first time I did this procedure. It was a struggle because his bones were so demineralized. But yesterday it was a breeze, his bones looked 30 years younger and had enough calcium and other minerals to provide beautiful fluoroscopic (live X-ray) images.

Joe is now sleeping with just 10 degrees elevation at the head of his bed (previously 90 degrees). His fatty liver disease is gone.

The Paleo diet allowed this elderly gentleman to lose 90 pounds, improve his exercise tolerance dramatically (he just won a metal detecting contest competing against young adults) and significantly improve his bone strength. It also cured his fatty liver disease.

Not bad for just limiting food to fresh vegetables, fresh fruits, meat, seafood, nuts and eggs.

Joe’s improvement is not a surprise. A study done at UCSF on the metabolic ward demonstrated improved calcium metabolism (reduced urinary excretion of calcium)  within 2 weeks of placing young “couch potato” adults on a paleolithic diet. It also demonstrated improvements in blood pressure, glucose tolerance, decreased insulin secretion, increased insulin sensitivity and improved lipid profiles in just a few weeks. This occurred without an exercise program (exercise will enhance bone strength, reduce blood pressure, improve insulin sensitivity and improve lipid profiles) and without weight loss. The subjects were “force fed” to avoid weight loss so the beneficial effects of the dietary change alone could be analyzed without the con-founder of weight loss. You can read the abstract of this study here.

The improvements in calcium metabolism are not mentioned in the abstract but appear in the full article in Table 1.

Joe is very grateful for the tremendous improvement in his quality of life, primarily achieved by adopting a Paleo-diet.

Until next time.

BOB Hansen MD