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Perhaps solve the other pandemic: Vitamin D deficiency — to help beat Coronavirus?

Sun, photo, Chuttersnap

Missing out on the Sunshine Vitamin?

We’re throwing billions at Coronavirus but missing cheap wins.

After masks and soap, the next bargain to reduce the impact of coronavirus is Vitamin D supplements.

Vitamin D deficiency is so common it’s an epidemic affecting a billion people around the world. Ponder that half the population of many western nations are clinically deficient by the end of winter. Add that to a novel virus and consider that higher Vitamin D levels reduce the risk of respiratory tract infections like influenza by as much as 40%.

As Grant et al say:

“Low vitamin D status in winter permits viral epidemics.”

Vitamin D levels also correlate with lower rates of cancer, diabetes, high blood pressure, asthma, heart disease, dental caries, preeclampsia, autoimmune disease, depression, anxiety, and sleep disorders. Vitamin D influences over 200 genes. It’s so crucial, it was likely the reason northern Europeans evolved whiter skin. The lack of sunlight and the introduction of grains in diets (as opposed to eating liver and whales) meant that Europeans weren’t getting enough D from either food or sun. The selective pressure was so strong that lighter skin rapidly took over all the northern communities. Eskimos didn’t need to go white — they were still getting D from offal and plenty of fish.

Unlike most vitamins, D is also correlated with “that holy grail” —  a reduction in all cause mortality. So even if a D supplement doesn’t help against coronavirus, side effects include less cancer and fewer heart attacks. Not too shabby for a five cent supplement.

The cost of one night in intensive care would provide vitamin D supplements for a month for 3,000 people.

Cholecaliferol, Vitamin D3

Vitamin D or Cholecalciferol, is probably one of the main reasons that coughs and colds and death itself, almost always peak in winter when people have lower vitamin D levels. Of course, winter is also a happy-hour for most viruses because temperatures are cooler and people crowd indoors more.

Researchers Grant et al, put out a call for people to supplement with D during this pandemic, pointing out that this will reduce the incidence of the co-morbidities that are hit hardest by Coronavirus. They also point out that D reduces respiratory tract infections, and is actively involved in our own anti-viral defences in at least three different ways. Vitamin D induces cathelicidin and defensins (polypeptides that our immune system uses like surface-to-air missiles against bacteria or enveloped viruses). D also reduces production of proinflammatory cytokines (the messengers that elict the deadly cascade of inflammation).

Vitamin D inhibits cytokines and reduces lung injury and a deficiency contributes to ARDS:

...more and more evidence indicates that vitamin D is involved in regulating various cells of the innate and adaptive immune system [13]. Vitamin D has a broad role in regulating inflammatory responses in models of inflammations [14], [15], [16]. Vitamin D receptor knockout mice which were treated with LPS, displayed a more distinct inflammatory response than wildtype mice [17]. In addition, we previously demonstrated that vitamin D deficiency (VDD) contributed directly to the ARDS…

— Zheng et al (2020)

People with low levels of vitamin D are more than 2.5 times as much at risk of developing pneumonia than people with high vitamin D levels.

Vit D status and influenza like illness, graph.

As Vit D levels increase Influenza like illness decreases. Grant et al. Click to enlarge.

 About half the population may be deficient

And that’s before they spend weeks sheltering-indoors.

About half the population of Germany, the UK and Ireland could be classed as having a Vitamin D deficiency:

 Using serum 25(OH)D <50 nmol/L in the same surveys would translate to 44.9, 2.1, and 32.6 million individuals in Germany, Ireland, and the United Kingdom, respectively, having deficiency as defined by this threshold.

In the US 42% were found to be deficient, including 80% of blacks, 70% of hispanics. (Forrest et al 2011)

Deficiencies are more likely in older people which may also contribute to the demographics of Covid-19.

Obviously, deficiencies are much more likely in people with darker skins, especially in high latitude areas. If D were important in Covid cases, we’d expect to see a higher rate in blacks in higher latitude winter climates, and sadly that’s exactly what we see.  It’s confounded by a squadron of factors but in Chicago, Blacks have four times the chance of dying from Covid-19 as whites do despite being a similar percentage of the population. Obviously poverty and co-morbidities increase the risk, but low Vitamin D also helps create the co-mobidities.   h/t Bill in Oz

If D3 supplements reduced the risk of ARDS by even 10% it would be a bargain.

Lest you think this is just weak correlation, the bane of so many nutritional studies, there is not only a mechanism to explain why D might matter, but three:

Vitamin D Supplementation Could Prevent and Treat Influenza, Coronavirus, and Pneumonia Infections

Grant W.B. et al

Low vitamin D status in winter permits viral epidemics. During winter, people who do not take vitamin D supplements are likely to have low serum 25-hydroxyvitamin D [25(OH)D] concentrations. Vitamin D can reduce the risk of viral epidemics and pandemics in several ways. First, higher 25(OH)D concentrations reduce the risk of many chronic diseases, including cancers, cardiovascular disease, chronic respiratory tract infections (RTIs), diabetes mellitus, and hypertension. Patients with chronic diseases have significantly higher risk of death from RTIs than otherwise healthy people. Second, vitamin D reduces risk of RTIs through three mechanisms: maintaining tight junctions, killing enveloped viruses through induction of cathelicidin and defensins, and reducing production of proinflammatory cytokines by the innate immune system, thereby reducing the risk of a cytokine storm leading to pneumonia. Observational and supplementation trials have reported higher 25(OH)D concentrations associated with reduced risk of dengue, hepatitis, herpesvirus, hepatitis B and C viruses, human immunodeficiency virus, influenza, respiratory syncytial virus infections, and pneumonia. Results of a community field trial reported herein indicated that 25(OH)D concentrations above 50 ng/ml (125 nmol/l) vs. <20 ng/ml were associated with a 27% reduction in influenza-like illnesses. From the available evidence, we hypothesize that raising serum 25(OH)D concentrations through vitamin D supplementation could reduce the incidence, severity, and risk of death from influenza, pneumonia, and the current COVID-19 epidemic.

 Vitamin D levels are also lower in people who have heart attacks, diabetes, pnumonia, and they’re low in China, Italy and South Korea:

More important, people with chronic diseases have lower 25(OH)D concentrations and increased
inflammation. A study in Triese, Italy, reported that patients with a mean age of 67 ± 12 years
who developed acute myocardial infarction had mean serum 25(OH)D concentrations in winter
of 11 ± 2 ng/ml [52]. A study conducted in Wenzhou, China (28°N), on diabetics and control
subjects aged 43 ± 11 years reported that diabetics had mean 25(OH)D concentration of 13 vs.
16 ng/ml for control subjects [53]. An observational study conducted in Qinhuangdao, China,
compared serum 25(OH)D concentrations for hospital patients with pneumonia vs. those without
[54]. Serum 25(OH)D concentrations for those with pneumonia were 9 ± 2 ng/ml, whereas those
for the nonpneumonia group were 14 ± 4 ng/ml, p = 0.000.

People with low Vitamin D levels are twice as likely to die:

Bluntly, blood levels of Vitamin D are associated with all cause mortality. Your odds of dying from just about anything, except maybe car accidents, are almost twice as high if your blood serum levels are in the lowest quantile (0-9ng/ml) compared to the top quantile (above 35ng/ml). Mortality levels off  around 36ng/ml and higher (which is 90 nmol/l.)

Vitamin D and Mortality

Vitamin D and all cause mortality   Garland et al 2014

In other studies, mortality rises again at the highest levels of D

The same pattern has been found in study after study:

Twenty-five studies identified a significant inverse relationship between 25(OH)D concentration and age-adjusted all-cause mortality hazard rates (Figure 2). In 5 studies,21,34,35,37,47 an inverse trend was present, but was not statistically significant. In 2 studies, 1 in the United States48 and 1 in Linxian, China,50 no association was seen. — Garland, 2014

Dose — 1000IU per day

A target range of 25(OH)D of greater than 30 ng/mL could be achieved in most individuals by intake of approximately 1000 IU per day of vitamin D3,12 which is one quarter the National Academy of Sciences–Institute of Medicine tolerable upper level of intake of 4000 IU per day at ages 9 years and older.69

Garland et al 2014:

 Vitamin D levels in pregnant women affects a childs lungs six years later, brains ten years later and bones twenty years after they are born:

Vitamin D deficiency during pregnancy affects offspring. In a community-based study of 901 mother and offspring pairs, researchers found that maternal vitamin D deficiency (serum 25-hydroxyvitamin D < 50 nmol/L) at 18 weeks’ pregnancy was associated with impaired lung development at age 6 in offspring, neurocognitive difficulties at age 10, increased risk of eating disorders in adolescence, and lower peak bone mass at age 20. [121314]

Vin Tangpricha, M.D. PhD. Medscape (free but needs registration).

Vitamins mostly help people who are deficient (though as stated above, this is quite common with D). Any sole vitamin will have some downstream effect on other essential molecules which may be depleted.

The form D3 (cholecalciferol) is likely to help more than D2 (ergocalciferol). D3 is associated with a reduction in all cause mortality and a reduction of cancer risk, but D2 is not. High dose, longer term D supplements can cause deficiencies in other vitamins, like, Vitamin A. Ideally take Vitamin K as well (more on that at some other point). If you happen to supplement with boron beware that it may help bodies hang on to D3 levels for longer. There are, no doubt, a lot of other examples of complex interactions.

It is possible to have too much, but there is a big safety margin.

Ideally, we’d get a blood test to see if any supplement was needed, but it probably isn’t worth the risk in the current pandemic. Most of our Vitamin D comes from sun exposure, not from diet, though some people have lower levels due to genetic variations. Are you getting enough (and obviously, in Australia, not too much?) Most sunscreens will stop vitamin D production, and glass windows do too.

TILDA researchers in Ireland have put out a Covid and Vit D report recommending 400IU – 1000IU as a winter supplement or for high risk groups or housebound people. Ireland does not fortify foods with Vitamin D. Nor does China or South Korea.

If you want to eat your Vitamin D, head for Salmon, sardines, tuna, and Cod liver oil.  Eggs, too. But it’s difficult to get enough D from your diet. You need something like 9 oz of salmon a day.

PS: Best not drive out to get your vitamin D. People can post it.

Other info:  US National Institute of Health: Vitamin D and Covid-19

Abbreiviations: 25(OH)D is the best proxy for Vitamin D levels.

h/t to Sophocles. I’ve been meaning to write about D for ages.

REFERENCES

Grant W.B. et al (2020) Vitamin D Supplementation Could Prevent and Treat Influenza, Coronavirus, and Pneumonia Infections, Preprints 2020, 2020030235 (doi: 10.20944/preprints202003.0235.v1).

Holick (2016) The vitamin D deficiency pandemic: Approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord. 2017 Jun;18(2):153-165. doi: 10.1007/s11154-017-9424-1.

Forrest et al (2011) Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011 Jan;31(1):48-54. doi: 10.1016/j.nutres.2010.12.001.

Martineau, A.R. (2017)  Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data,  BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.i6583

Zheng (2020) Vitamin D attenuates lung injury via stimulating epithelial repair, reducing epithelial cell apoptosis and inhibits TGF-β induced epithelial to mesenchymal transitionBiochem Pharmacol. 2020 Apr 3:113955. doi: 10.1016/j.bcp.2020.113955. [Epub ahead of print]

Photo by chuttersnap on Unsplash

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