Got Sunshine? All About Vitamin D
A special look at how this hormone works in our immune system and lungs.
I have been getting quite a few questions about Vitamin D regarding how best to supplement with it - what form and what dose.
These questions are a result of Vitamin D popping up in the news as a good preventive measure for COVID-19 both to bolster immune response and to dampen the escalating inflammatory response, which can lead to Acute Respiratory Distress Syndrome (ARDS).
So I thought a bit of an explanation about what Vitamin D is, how it works in the body, what research is showing about its efficacy with COVID-19, and a discussion on the best way to supplement with it would be useful for many people. So let’s dive in!
Vitamin D is a really interesting vitamin because it is fat-soluble (only four Vitamins are - A, D, E and K) and it serves as a hormone precursor. It is a precursor because it is metabolically inactive. Vitamin D undergoes two reactions in the body to become active - once in the liver and once in the kidney. The kidney makes the 1,25OH-D3 (1,25-dihydroxyVitamin D3), which is the biologically active form in the body that functions as a steroid hormone.
Image source: https://www.2ndacthealth.com/wp-content/uploads/2016/05/Vitamindsyn.jpg (1)
This is a great image showing how the active form of Vitamin D is made in the body.
UVB light from the sun is absorbed by the skin and converts 7-dehydrocholesterol to Vitamin D3. At this stage the Vitamin D3 is called cholecalciferol. If you take a D3 supplement, this is the form you are taking it in - cholecalciferol.
Vitamin D3 then travels to the liver where it undergoes a hydroxylation reaction and is converted into 25-hydroxyvitamin D or 25OH-D. Another term for 25OH-D is calcifediol. If you ever had a blood test to test your Vitamin D levels, the most common test is to test blood levels of 25OH-D because it has the longest half life in the blood.
25OH-D then travels to the kidney where it is hydroxylated again to form either: 1) the active 1,25OH-D, also known as calcitriol, which increases blood calcium levels, or 2) the active 24,25OH-D, which decreases blood calcium levels. Whether 25OH-D converts to 1,25OH-D or 24,25OH-3 depends on the parathyroid gland, parathyroid hormone and serum calcium levels. But let’s not digress!
Once active Vitamin D3 is in the blood, it begins to work by binding to the various proteins such as VDR and GC. Once it binds to the protein, a cascade of actions is kicked off acting on:
✔ Calcium and phosphorous levels
✔ Bone mineralization and remodeling
✔ Dental health
✔ Innate and adaptive immune response modulation
✔ And the endocrine, glucose and cardiovascular systems.
So its not just the level of Vitamin D3 in your blood that is important but also your genetic pathways for Vitamin D metabolism.
Let’s take a look at the genes involved with Vitamin D activity:
VDR - This gene is for the Vitamin D receptor. It binds with Vitamin D and is involved in regulating inflammation, insulin-like growth factor signaling, estrogen-related pathways, calcium absorption in the stomach and intestines and bone strength. Gene variants such as having the A allele in VDR has been associated with reduced bone mineral density and osteoporosis.
The VDR is also expressed on immune cells (B cells, T cells and antigen-presenting cells) which means all of these immune cells are capable of synthesizing the active Vitamin D metabolite.
GC - This gene is for the vitamin D binding protein in the albumin gene family. This protein is found in plasma, cerebrospinal fluid, ascitic fluid and on the surface of many cell types. It binds to Vitamin D and transports it to target tissues. Having a C allele SNP in the GC gene is associated with a 49% increased risk for Vitamin D insufficiency.
CYP2R1 - This is a member of the cytochrome P450 family. It influences conversion of 25OH-D to its active form. Having the G allele SNP in this gene is associated with lower Vitamin D levels because the formation of the active form of D3 is being impacted. CYP21 has been found to be compromised in patients with COPD or asthma. (2)
Psssst... If you perk up about genes and how your diet and lifestyle choices can beneficially impact your genetic expression. Or hey, if you are curious what your genes look like (who isn't?), sign up for my Nutrigenome™ program. You will learn all about your genetic pathways and get a personalized treatment plan. It’s awesome. You’ll love it!
Vitamin D and COVID-19
Our immune cells have the Vitamin D receptor (VDR) on them. When Vitamin D binds to this receptor it sets off the following chain reaction of events.
In our innate immune response Vitamin D helps to reduce inflammation and cytokine production. That is the ↓ IL-1, IL-6 and TNFa in the below image.
In the adaptive immune response Vitamin D suppresses T cell proliferation, shifts towards a Th2/Treg balance and inhibits Th17 lowering IL-17.
(By the way, Vitamin D’s effect on the immune system also explains its treatment role for autoimmune diseases including RA and Lupus as well as inflammatory diseases such as IBD).
Now let’s discuss Vitamin D and everyone’s favorite virus of the moment…
As discussed above, Vitamin D3 has positive effects on both the innate and adaptive immune system. In addition to these benefits, when Vitamin D binds to VDR, it “may generate beneficial effects in ARDS by decreasing the cytokine/chemokine storm, regulating the renin-angiotensin system, modulating neutrophil activity and by maintaining the integrity of pulmonary epithelial barrier, stimulating epithelial repair and tapering down the increased coagulability.” (3)
1,25OH-D3 also impacts ACE2, the host cell receptor that protects against acute injury in the lung and mediates infection by SARS-CoV-2. (4)
Multiple research studies were conducted in Europe to assess correlation between geographical location, 25OH-D levels and COVID-19 infection and mortality. All studies found that “the correlation between 25OH-D concentration and mortality rate reached conventional significance” (5) with countries that had lower mean concentrations of 25OH-D experiencing higher infection and death rates. (5)
I'd like to note here that testing serum 25OH-D levels is our best method for testing Vitamin D but it does not tell the whole story about Vitamin D3 efficacy in the body. If Vitamin D3 is not being converted to the active metabolite, or if the Vitamin D related genes have certain alleles that result in reduced binding, the Vitamin D in the blood might not be utilized properly.
Multiple studies have been done to assess the positive effect of Vitamin D on patients with COVID-19. One study showed that administration of oral 1,25OH-D to COVID positive patients resulted in less severity of the disease including reduced rate of ICU admission and reduced mortality. (3)
Checking your Vitamin D levels
Concentration of 25OH-D in the serum is the common test for Vitamin D levels. This can be run through Quest or an in-office dried blood spot test.
I prefer to use the in-office dried blood spot test as most insurance does not cover Vitamin D testing unless you have a specific diagnosis such as osteoporosis.
Vitamin D deficiency <20ng/ml
Vitamin D insufficiency <30ng/ml
Vitamin D sufficiency range 30ng/ml - 100 ng/ml (6)
I like to see Vitamin D levels around 50 ng/ml unless there is autoimmunity in which case I prefer to see Vitamin D between 50-80ng/ml. If there is a medical history of osteoporosis, autoimmunity, eczema, prone to multiple infections, asthma, etc. I also like to look at the individual's Vitamin D genetic pathways.
Take caution: you can have too much Vitamin D as well. <100ng/ml could result in hypercalcemia, hypercalciuria, fatigue, anorexia, nausea and vomiting.
Getting your Vitamin D levels into that optimal range
Individuals living in northern latitudes have a tendency to have lower Vitamin D levels due to less sunlight exposure. Here are a few treatment recommendations to boost your Vitamin D levels, especially in the winter.
Sunshine: Vitamin D is known as the sunshine drug! The absolute best way to raise Vitamin D levels is through sun exposure. 30 minutes in the sun around noon time with face, arms and legs exposed to the sun (no sunscreen!) can provide between 2,000-8,000IU / day. (6)
Nutrition: Eating Vitamin D rich foods such as cold water fish (salmon, mackerel, herring), sardines, tuna, halibut, butter, egg yolks, lamb, beef, pork and cod liver oil. Many foods are also fortified with Vitamin D such as milk. Sun-exposed mushrooms have high levels of D2 (ergocalciferol) which can also be used to raise Vitamin D levels in the body.
Supplements: Vitamin D is fat soluble, so taking your Vitamin D supplement with a little bit of fat will increase its absorption. Please note that if you have compromised fat digestion such as gallbladder or pancreatic disease, celiac disease or IBD, vitamin D will not be well absorbed in the gut.
To bypass that first step of metabolism, I prefer to give Vitamin D supplement in an oil-based, emulsified form. This form absorbs directly in the mouth and travels in the blood to the liver to undergo its first hydroxylation and avoids any potential digestive issues that could reduce Vitamin D absorption.
Dose: As a naturopathic doctor, I treat the individual and each case is unique. I recommend 2000-5000 IU/day depending on the individual’s vitamin D levels, symptoms, medical history, genetic profile, medication use, diet, time spent outdoors and time of year. If the patient is severely deficient, I will go up to 10,000 IU/day for several months. I recommend 400-800IU/ day for children.
In some cases it is best to administer Vitamin D together with Vitamin A, Vitamin K and Mg.
Please note that because Vitamin D is fat soluble it gets stored in our fat. As a result, toxicity can occur. Please do not self-treat yourself with Vitamin D. Get tested and work with a knowledgeable doctor to supplement properly. Special care should be taken by pregnant and lactating women.
Medications: There are multiple medications that reduce vitamin D absorption and efficacy in the body including Cholestyramine, Cimetidine/Tagamet, Colestipol, Corticosteroids (including Prednisone), Heparin, Phenobarbital and Phenytoin. If you are taking any of these medications, you should have your Vitamin D levels tested.
As we move into winter, Vitamin D is a helpful hormone to have circulating in our body and working in our favor.
If you are interested in getting your Vitamin D levels tested, checking the robustness of your vitamin D pathways, and being advised on the best Vitamin D supplements to take, please set up an appointment with me.
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Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM, et al. “Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study.” The Journal of Steroid Biochemistry and Molecular Biology. 2020;203:105751. doi:10.1016/j.jsbmb.2020.105751
Ilie PC, Stefanescu S, Smith L. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality. Aging Clinical and Experimental Research. Published online May 6, 2020. doi:10.1007/s40520-020-01570-8
Laird E, Rhodes J, Kenny RA. Vitamin D and Inflammation: Potential Implications for Severity of Covid-19. Irish Medical Journal Vol 113 No 5 P81.http://imj.ie/wp-content/uploads/2020/05/Vitamin-D-and-Inflammation-Potential-Implications-for-Severity-of-Covid-19.pdf
Alan Gaby. Nutritional Medicine, Second Edition. Editorial: Concord Fritz Perlberg Publishing; 2017
Tee S, Panagiotou G, Ihsan Y, et al. Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID-19 are associated with greater disease severity. Endocrine Abstracts. Published online August 21, 2020. doi:10.1530/endoabs.70.oc6.6
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