PREPRINT
Key Words: vitamin D, innate immunity, respiratory infections, COVID-19, SARS-CoV-2, sunlight
Summary
Acute viral respiratory infections, including COVID-19, are strongly correlated with vitamin D insufficiency. They are also strongly seasonal, peaking in the winter, when the availability of the UVB component of sunlight is low. UVB is known for inducing production of vitamin D in the skin. However, vitamin D supplementation has shown little or no effect in the prevention of respiratory infections in adults. Thus, UVB light provides the immune system with essential benefits that are not produced by oral vitamin D supplements.
This paper posits that UVB light stimulates production of cathelicidin and other antimicrobial peptides (AMPs) in the skin. These AMPs are carried by the blood to the respiratory tract and enhance innate respiratory immunity. AMPs are also referred to as “natural antibiotics,” because they protect not only against microbes but also enveloped viruses, including influenza and coronaviruses.
The skin and respiratory tract surfaces play a similar role in the body – acting as a barrier between the body and the external world. Many of the same AMPs, including cathelicidin, are produced and act in the skin, the respiratory tract surface, the intestines, and some blood cells. Cathelicidin is carried by the blood.
This paper provides additional evidence that exposure to UVB in sunlight or artificial UVB sources, in safe amounts, depending on skin phototype (dark skin might need 5-6 times more exposure than light skin), is necessary for maintaining normal innate immunity. Vitamin D supplements cannot replace UVB exposure.
Intro
Infection Seasonality
Currently (at the end of November 2020), the increase in COVID-19 infections, in the northern hemisphere, matches seasonality expectations. COVID-19 is not an exception among respiratory infections. Its seasonality has been observed in both hemispheres. The inverse correlation between sunlight UV and SARS-COV-2 positivity [1] has been reported. The increase in COVID cases is happening slightly ahead of the regular flu season. A significant part of the population has had less than usual sunlight exposure in the previous months, due to COVID-19 precautions.
The seasonal character of influenza has been noted for long time [2]. This seasonality is linked to low exposure to the UVB (wavelengths 280-320 nm) component in sunlight, which results in insufficient levels of vitamin D. Among other effects, vitamin D is required for AMPs production, so the increase in the respiratory infections in winter was linked to seasonal impairment of the AMPs production [3]. In the US, respiratory infections boom in the winter and almost disappear in the summer and the death rate is 25% higher in the winter than in the summer [4]. Many observational studies have shown that moderate UVB exposure led to sharp decrease in respiratory infections [5]. [6] reports weekly inverse correlation between sunlight and spread of 2009 H1N1 zoonotic influenza virus (“swine flu”).
The lack of UVB exposure and low levels of vitamin D are strongly associated with each other and with a susceptibility to respiratory infections. The hypothesis that UVB exposure can be replaced with vitamin D supplementation, in order to maintain innate respiratory immunity, has somehow become entrenched. This flawed belief continues to persist despite multiple studies in which oral supplementation with vitamin D has shown no or little respiratory immunity benefits [7].
Although common wisdom in mid latitudes of Europe held that moderate exposure to sunlight is beneficial [8], such research has not been encouraged [9].
Vitamin D
Vitamin D3 is produced by the skin when it is exposed to UVB light. It can also be also ingested with the food. Either way, it is inactive until metabolized in the liver to 25(OH)D (25-hydroxy-vitamin D). 25(OH)D then further metabolizes to 1,25(OH)2D3 (1.25‐dihydroxyvitamin D3) in the kidneys as well as many other organs, including the skin and epithelial cells of the respiratory tract.
Innate Immune System & AMPs
The human innate immune system responds to pathogens without the need to recognize them. This is in contrast to the adaptive immune system, which needs to recognize the particular pathogen, before counteracting it with antigens or T-cells.
This makes AMPs critically important in the defense against novel respiratory viruses, such as SARS-CoV-2, which are not recognized by the body. Cathelicidins and other AMPs are the tools of the innate immune response. Cathelicidins dissolve viral and microbial membranes, and also alert the rest of the immune system to act [10], [11]. LL-37 (having precursor protein hCAP18) is the only known human cathelicidin. In the skin, cathelicidin serves as a chemical shield. Cathelicidins are produced from keratinocytes [17], in many tissues in the skin to epithelial cells of the lungs [12]. Some blood cells also produce AMPs.
Cathelicidin production in the skin is induced by UVB (as explained below), or by the local injury or infection [10].
Results
For a long time, it has been observed how rarely sunburns (severely damaging skin and suppressing adaptive immune system) lead to opportunistic infections.
When the skin is damaged, AMPs are produced. Their primary role is the local anti-microbial protection of the damaged skin, but they also travel in the blood [13] and can protect respiratory tract. LL-37 was shown to directly inhibit the influenza virus in humans [14].
In 2005, Mallibris et al. conducted a study, in which they exposed buttocks of eight volunteers to UVB [15]. The study summarized the results in the title “UVB Upregulates the Antimicrobial Protein hCAP18 mRNA in Human Skin.” One-time exposure of a single buttock to the minimal erythema dose of UVB led to 2.3x increase of hCAP18 level in the exposed skin, within 24 hours. This amount of UVB cannot significantly increase the body’s vitamin D levels. Thus, the production of extra hCAP18 was solely due to the UVB stimulation, not increased vitamin D levels.
Zasloff [16], concluded cautiously that sunlight “activates an arm of innate immunity within the skin.” In addition to hCPA18/LL-37 production, Zasloff suggested a few other mechanisms.
Other experiments [17] with UVB successfully induced defensins and other universal AMPs in keratinocytes. This lead to the conclusion that UVB exposure increases local production of AMPs and boosts innate immunity [18].
In hindsight, it is not that surprising that the skin reacts to ultraviolet irradiation similarly to how it reacts to other stimuli, such as physical injury or infection.
UVB light might increase production of AMPs in the skin through increased local production of 1.25‐dihydroxyvitamin D from 25(OH)D. Cathelicidin and other AMPs, produced in the skin, travel in the blood to other parts of the body, including the epithelial surfaces of respiratory system, boosting innate respiratory immunity. It is also possible that UVB activates blood cells, passing through the exposed skin and capable of producing AMPs (neutrophils, macrophages, lymphocytes, etc.), and they produce AMPs in other tissues as well.
Vitamin D Supplementation does not noticeably increase LL-37 levels in the blood [19], [20], even when it significantly increases 25(OH)D levels.
Discussion
[20] reported that a subgroup of the experiment subjects had ~20% increase of LL-37 concentrations, corresponding to 200% increase in 25(OH)D concentrations in the blood following ergocalciferol supplementation. This relation is insignificant, and might be explained by their initial deficiency of 25(OH)D and/or sunlight exposure, not known the to researchers
[19] demonstrated a decrease in sickness with supplementation. The supplementation was Vigantol – vitamin D3 dissolved in triglyceride. Multiple studies from 1930s demonstrated significant improvement of respiratory immunity from taking cod liver oil [5], which contained not only vitamin D, but also Omega-3 fatty acid, and vitamin A. The effect of combined vitamin D / Omega-3 supplementation is a promising avenue for research. A word of caution: some sources say that modern techniques of cod liver and other fish oil preparation remove most vitamin D.
[21] and [22] reported an inverse correlation between sunlight UV and COVID-19 mortality,. This might be due of the anti-inflammatory effect of vitamin D and is out of the scope of this paper.
Conclusions
Exposure to UVB in sunlight or artificial UVB sources, in proper amounts and adjusted by skin phototype (dark skin might need 5-6 times more exposure than light skin), is necessary for maintaining normal innate immunity. Vitamin D supplements do not produce the same benefits or immunity as UVB exposure. UVB stimulates production of cathelicidin and other AMPs in the skin and/or certain blood cells travelling through skin. These AMPs are carried by the blood to the respiratory tract surfaces and enhance innate respiratory immunity.
No Competing Interests
The author declares no competing interest.
No funding was provided for this work.
Acknowledgements
Thanks to AO for the contribution to this paper.
An author's remark
- I bent backward in order not to say that the ozone hoax is behind the suppression of the research on the UVB health benefits. Nevertheless, this article has been rejected by preprints.org.
- People who wear masks outside further decrease the amount of the beneficial UVB.
- The innate immunity is surprisingly rarely mentioned in the discussions of the response to COVID-19, but it is what protects most people from getting sick when from exposure to SARS-COV-2.
References
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[2] CANNELL JJ, VIETH R, UMHAU JC, HOLICK MF, GRANT WB, MADRONICH S, et al. Epidemic influenza and vitamin D. Epidemiol Infect 2006;134:1129–40. https://doi.org/10.1017/S0950268806007175.
[3] Cannell JJ, Zasloff M, Garland CF, Scragg R, Giovannucci E. On the epidemiology of influenza. Virol J 2008;5:29. https://doi.org/10.1186/1743-422X-5-29.
[4] Grant WB, Bhattoa HP, Boucher BJ. Seasonal variations of U.S. mortality rates: Roles of solar ultraviolet-B doses, vitamin D, gene exp ression, and infections. 19th Vitam Workshop 2017;173:5–12. https://doi.org/10.1016/j.jsbmb.2017.01.003.
[5] Umhau J. Vitamin D and Influenza 2008.
[6] Slusky DJG, Zeckhauser RJ. Sunlight and Protection Against Influenza. Econ Hum Biol 2020:100942. https://doi.org/10.1016/j.ehb.2020.100942.
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[17] Gläser R, Navid F, Schuller W, Jantschitsch C, Harder J, Schröder JM, et al. UV-B radiation induces the expression of antimicrobial peptides in human keratinocytes in vitro and in vivo. J Allergy Clin Immunol 2009;123:1117–23. https://doi.org/10.1016/j.jaci.2009.01.043.
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[19] Bergman P, Norlin A-C, Hansen S, Rekha RS, Agerberth B, Björkhem-Bergman L, et al. Vitamin D3 supplementation in patients with frequent respiratory tract infections: a randomised and double-blind intervention study. BMJ Open 2012;2:e001663. https://doi.org/10.1136/bmjopen-2012-001663.
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THANKS for the very interesting paper !
For easy measurement of UVB from either sun or UV lamps… this meter will give results in µW/cm²:
https://www.solarmeter.com/product/model62/
For shortwave UVB, the erythemally weighted models 7.0 and 7.5 relate directly to D3 synthesis. And model 6.4 converts D3 effective UVB into IU-equivalent per minute of exposure.
Aside from Planned Parenthood et al, have there been excess deaths, attributable to Covid-19 and Planned Parent?
Government Lies Exposed By… Government
There has been no dislocation in government benefit payments. A separate post in the Johns Hopkins student paper, now removed, but archived, and restored, argues that there have been no statistically significant changes in year to year total deaths.
A closer look at U.S. deaths due to COVID-19
Editor’s Note: After The News-Letter published this article on Nov. 22, it was brought to our attention that our coverage of Genevieve Briand’s presentation “COVID-19 Deaths: A Look at U.S. Data” has been used to support dangerous inaccuracies that minimize the impact of the pandemic.
We decided on Nov. 26 to retract this article to stop the spread of misinformation, as we noted on social media. However, it is our responsibility as journalists to provide a historical record. We have chosen to take down the article from our website, but it is available here as a PDF.
Interesting.
“However, vitamin D supplementation has shown little or no effect in the prevention of respiratory infections in adults.”
I am not convinced that COVID-19 is really a respiratory infection. Several early reports found COVID to affect the lungs last. The first thing that was noticed was the bloods inability to carry oxygen. This would lead to organ damage and the bodies response to the organ damage lead to lung infections.
Wouldn’t a respiratory virus hit the lungs first?
With time I think medicine will have to admit how wrong they have been.
“…multiple studies in which oral supplementation with vitamin D has shown no or little respiratory immunity benefits [7].”
Huh? ‘
[7]…https://doi.org/10.1136/bmj.i6583
“…Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the mostbenefit.”
This report offers the same conclusion:
https://www.sciencedirect.com/science/article/pii/S0960076020302764
Reports I’ve read that claim to prove the ineffectiveness of Vitamin D all used risibly low dosages, such as 2000iu, that are arguably insufficient to sustain even “adequate” blood levels in the absence of sunlight.
I am astonished that no mention has been made of a complementary zinc daily dose. At the onset of Coronavirus epidemic, our GP daughter delivered to us (deemed to be in a very vulnerable group) a tub of Vitamin D3, 25 microg, PLUS High Strength Zinc (Gluconate), 15 milligrams; with instructions to take one of each per day.
We have done that and continue to do so. Moreover, both of us are just emerging from having been positively tested with the virus. We have found the symptoms were barely that of a very mild dose of flu’, other than the tiresome loss of taste and smell which is now slowly beginning to recover. Certainly we have not had our daily activities curtailed in any way.
Given there has been published articles on this combination months ago I am not impressed with current standards of academia. Fearmongoring seems to be the driving pattern of their efforts as those of the elites both national and international, not truth.
In biology the more you look for the more you find.
But knowledge is not understanding.
By spinning an endless alphabet soup of new proteins and receptors and genes and pathways one creates the impression that knowledge is advancing but it is not.
A theory becomes popular or useful and it is incredibly easy to spin a bio-story with new alphabet soup of molecular players in a signalling cartoon, to wow the masses.
But it is easy for such decorated narrative to lead people down the garden path, for abundance of bio-information to be mistaken as knowledge.
It’s too easy to spin an alphabet soup argument to support whatever position you like.
Voluminous molecular-genetic research in big Pharma is NOT resulting in more new drugs, instead they complain of empty pipelines so they resort to finding new applications for old favourites.
And there have been colossal failures like the stomach ulcer story and the unsaturated fats fairy tale.
“The lack of UVB exposure and low levels of vitamin D are strongly associated with each other and with a susceptibility to respiratory infections. The hypothesis that UVB exposure can be replaced with vitamin D supplementation, in order to maintain innate respiratory immunity, has somehow become entrenched. This flawed belief continues to persist despite multiple studies in which oral supplementation with vitamin D has shown no or little respiratory immunity benefits [7]”
“[7] Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017;356:i6583. https://doi.org/10.1136/bmj.i6583”
“Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit”
Did you ever read [7]?
Obviously not.
Leo Goldberg is a quack.
This article recommends UVB rays that cause aging , cataracts and skin cancer
That is the advice of a fool
Or a dermatologist who wants more business
This article should be deleted from this website
And quack Leo Goldberg should be permanently banned.
Unless promoting bad advice is a goal here.
You are quick to judge Richard, the effects you mention do not occur in populations with a sufficient intake of unmodified Omega 3 and Omega 6 fats. Highly processed seed sourced cooking oils make for poor cell membrane, and excess Omega 6 oils, common in the Western diet, are inflammatory, leading to weak blood vessels leading to many degenerative diseases.
I found by personal experience that a lifetime of sun exposure was causing the usual signs of skin ageing. A cancer diagnosis indicated a change to a healthy diet of mainly raw vegetables and fruit, including 45mls of Flaxseed oil, cold pressed, refrigerated and blended with high protein yogurt and ~40grams of freshly ground flax seed.
It was pleasantly surprising to find that after a few months of this, old moles dried up and fell off, so too skin- tags, and the crocodilian wrinkles of an 81 year old were replaced with a smooth skin and a sheen.
I still get plenty of sun, never use sunscreen but sensibly cover up on high UV days here at 32* S and 1000mtres altitude. At 88 now I get complimentary remarks about my skin and lack of wrinkles, a friend at lectures we both attend said she nearly fell off her chair when she heard how old I was. Castor oil applied regularly to any blemish that appears has meant no skin excisions either,
The cancer is still there, but I thank it for a change of lifestyle that keeps me flexible in joint, actively fit and thoroughly enjoying the life I have.
How much exposure is enough to per day to get the necessary dosage for protection?
Light brown to white skin tones.
What is the “proper amount” of exposure?
There are sensible, working, health professionals who may strongly disagree with this statement.
The guy, in the link below, is one such. He has produced many good videos on youtube, especially since Feb/March. This one is probably his first video on the efficacy of Vitamin D in respiratory infections and I recommend watching his later ones too. (As well as most of his videos).
https://www.youtube.com/watch?v=W5yVGmfivAk&t=1044s
Separately, and more generally, especially for male readers, I post another link about Vitamin D and treatments for prostate cancer and individuals with Benign Prostatic Hyperplasia (BPH, enlarged prostate gland).
https://www.youtube.com/watch?v=NqblQNt-HIg
This is real medical-trial research by real doctors on real patients with real prostate cancer or real BPH).
I recommend watching it carefully.
If nothing else, it puts to bed most scare stories you may read about the likelihood of vitamin D overdose toxicity. In this video (and I recall he may have another one or two related ones available on the internet) he also makes the case for just how much more Vitamin D most humans should be taking.
Except for those spending a lot of time outdoors in sunny climates with little clothing, the likelihood is we would all mostly benefit from much higher vitamin D intake. It also makes sense from an evolutionary perspective.
Would the UVB lamps used in pet reptile cages be an appropriate artificial source?
This is a scientific paper preprint. It is not intended to cover anything but its narrow subject.
Vitamin D supplements have their place in prevention of diseases of bones and inflammatory conditions, and even ARDS in COVID-19.
Both excessive and insufficient sun exposure are harmful. Optimal amounts depend on the skin type, latitude, time of year and day. It is always better to expose a large part of the body for shorter time than a small part for longer time.
With 1/4 of the body, there is a broad range of exposures providing enough UVB for vitamin D but causing no skin redness.
Wearing short pants and sleeves == 1/4 of the body
Face only == 1/16 of the body
Face under mask outdoors == idiot
Hey Leo G,
Thanks for the paper and discussion.
I am having a hard time digesting some of the comments and sediments from some of the folks here on this subject from people who I thought were better than your average leftist “person”; they (some of the long time contributors and posters) have actually allowed themselves to fall for the leftist cancel culture.
We all need to look in the mirror to make sure we are questioning the idea and subject and not attacking the person for having an idea. A lot of you failed to do that this time around. Go back and read your own comments objectively. There’s a lot of vitriol embedded in them.
I will leave with what I hope is a useful contribution; and frankly with a good thumb poke in all the naysayers’ eye:
I do not have a link to this paper. Only a pdf:
S236 | Public Health Then and Now | Peer Reviewed | Hobday and Cason
American Journal of Public Health | Supplement 2, 2009, Vol 99, No. S2
“The Open-Air Treatment of Pandemic Influenza” – Richard A. Hobday, PhD, and John W. Cason, PhD
Maybe the sun facilitating higher production of Vitamin D and AMP, getting people out of breathing the same diseased air and thus lowering the invasive biological burden is the actual why of the better outcomes. Perhaps we need to re-examine why these outdoor or open-air treatment centers produce better outcomes given Leo Goldstein’s paper. I have many papers discussing the benefits of open-air treatments.
At the practical and pragmatic level I will continue to institute an active Sun healthy lifestyle. Being in Texas now I will have good strong Sunshine available more often through out the year.
Note to MODS: posting from my laptop; normally my mobile.