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Cytokine Storm: What do age, Vitamin D, and genetics have to do with it?

 

Today I learned of 2 people that died of SARS Covid-19 this past week. One died over Thanksgiving weekend. He was the father of one of my good friends from residency. He was in good health, but in his 70’s. The other was a cardiologist at a local hospital that was seeing patients as usual 2 weeks ago, but died last week in the ICU of the hospital where he worked. He was also in his 70’s, and had heart issues of his own.

I know dozens more, some in their 70’s but mostly younger, that have contracted the virus and have had minimal symptoms. Most recovered quickly, and have had no repercussions.

What’s the difference?

Do we know why some recover with a box of tissues and some rest, while others get much sicker, or even lose their lives? This virus is everywhere. Assuming we are doing everything we can to reduce exposure, how can we shore up our defenses if we do get sick? How do we stay out of the ICU?

It turns out we do have some idea. And armed with that knowledge, we can be more prepared. There are 3 contributing factors I’d like to address: an aging immune system, Vitamin D levels, and genetically determined inflammatory response.

Aging

Aging can lead to a weakening of the innate immune system. This is the branch of the immune system that reacts to viral infections. If innate immunity is weak, the virus can infect and multiply quickly, leading to a much higher response of the adaptive immune system, which generates cell signaling chemicals called cytokines. This cytokine response can get out of control leading to the dreaded “cytokine storm”. This produces an excessive inflammatory response, especially in the lungs. This can lead to acute respiratory distress syndrome, pulmonary edema, and multi-system organ failure.

Vitamin D

We now know Vitamin D can suppress cytokine production in 2 ways: by boosting the innate immune system, and reducing the viral load, and by down regulating cytokine production and preventing cytokine storm. In fact, several very recent studies have shown low levels of 25-OH Vitamin D, defined in most studies as less than 30 ng/ml, is highly associated with a worse outcome, or even death, from Covid-19.

Older adults are at higher risk of Vitamin D deficiency due to a lower production of Vitamin D in the skin in response to sunlight, less time outdoors, and reduced dietary intake. Despite that, Medicare will only pay for a Vitamin D test once a year. However, it is arguably one of the most important biomarkers to follow.

Genetics

So, what about the younger people that are dying or have severe Covid-19 symptoms? It turns out, our genetics determine a lot about the way our immune system works. For example, one of the cytokines called Interleukin-6, or IL-6, can be markedly overproduced in response to an infection due to a genetic polymorphism that is fairly common. Another gene, STAT4, helps control inflammation, and when a single or double mutation is present, cytokine storm is more likely to occur. If you have a genetically higher risk of uncontrolled inflammation, you can take steps to reduce the likelihood of complications.

Takeaways

So, we can’t turn back the clock on an aging immune system, but we can arm ourselves with knowledge by checking Vitamin D levels regularly and supplementing to get low levels up into the protective range. Experts now recommend a 25-OH Vitamin D level of 40 to 60 mg/ml for immune and inflammation support. For those with an increased risk genetically, I would recommend aiming for levels of 60 to 80.

There are very few risks associated with taking Vitamin D. It does increase the absorption of calcium, so for those with a history of kidney stones, it can theoretically increase the chance of them forming, especially if you are also taking calcium. That calcium can be deposited in soft tissues and blood vessels, so to prevent this you have to take a combination Vitamin D3 with K2, and get adequate magnesium.

For anyone with critically low levels of Vitamin D, I recommend 10,000 IU of D3 with K2 daily for 8 weeks, then recheck levels.

For anyone with levels in the recommended range of 40 to 60 that wants to maintain or get it a little higher, take 2,000 – 5,000 IU daily.

Levels above 100 mg/ml can be associated with headaches and fatigue, so it’s important to monitor at lease every 6 months. It’s also a good idea to monitor calcium levels when on higher doses.

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465887/pdf/40520_2020_Article_1677.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541915/pdf/fimmu-11-558898.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567864/