(This was posted earlier in June 2016. Updated Oct 2019)
In recent years vitamin D deficiency has become like an epidemic all over the world. .Many people are surprised when I talk about severe vitamin D deficiency in my patients from India. In fact studies ((1))have shown that the incidence of vitamin D deficiency is 40-99% in India! We have become vitamin D deficient because we do not spend adequate time in the sun. But I am not sure how many of you will be outdoors in minimal clothes at temperatures of 40 degrees C and 90%+ of humidity! 🙂 If vitamin D deficiency is so common, should you be concerned about it?
Consequences Of Vitamin D Deficiency
Most of you are familiar with the action of vitamin D in protecting your bones and maintaining blood calcium levels—the “classical” actions of vitamin D.In fact,Sir Edward Mellanby (1884–1955) discovered Vitamin D and its potential role in preventing rickets about a hundred years ago. (Rickets is a softening and weakening of bones in children, causing severe deformities. This is a consequence of severe and prolonged vitamin D deficiency.) However, scientific studies in the last several years have shown that vitamin D has several other actions as well—the “non-classical” actions.
As you can see in Figure 1 above, vitamin D has numerous actions in the body. In fact, vitamin D is now considered to be more of a hormone rather than a vitamin. Unlike vitamins, your body has the ability to make vitamin D.Besides autoimmunity, low vitamin D levels are associated with many diseases like heart disease, diabetes, some cancers, hypothyroidism and many more. This makes it imperative to maintain optimal levels of vitamin D in your body.
Functions Of Vitamin D
Almost every cell in your body has vitamin D receptors. However, the following are the most important.
- Bone
- Calcium regulation
- Gene expression.
- Breasts
- Prostate
- Heart
- Muscles
- Intestine
- Immune regulation.
Vitamin D and the Immune System
Some of the earliest studies on vitamin D deficiency and autoimmune diseases have come from studies in people with Multiple Sclerosis. The incidence of MS is higher in northern latitudes ((2))People in these parts of the world receive less sunlight in winter. Sunlight exposure AND Vitamin D deficiency are both considered important factors in explaining this relationship with MS.
Vitamin D’s immune regulatory actions make it an important factor in your risk for other autoimmune diseases as well. In the immune system, vitamin D acts on
- Vitamin D modulates the activity of Th17 cells ((3)), which are known for their role in autoimmunity.
- Dendritic Cells. These are antigen-presenting cells that play a pivotal role in regulating innate and adaptive immune responses. Dendritic Cells ((4))are also important in maintaining immune tolerance. (Loss of tolerance to self is one of the ways in which you develop autoimmunity).
- Actions on B, T cells ((5)) and macrophages.
How Is Vitamin D Made In Your Body?
As you can see in Figure 2,
- In the skin, 7-dehydrocholesterol is converted by UV light into vitamin D3 (cholecalciferol).
- Vitamin D from food is in the form of D2 (Ergocalciferol). It has to be converted further.
- Vitamin D2 and D3 are prohormones. They are transformed in the liver to produce 25 hydroxyvitamin D (Calcidiol).
- Further conversion occurs in the kidneys to produce 1,25 dihydroxy vitamin D. This is the active form of the hormone. (This is why vitamin D levels need to be monitored in chronic kidney disease)
1,25 Dihydroxyvitamin D (Calcitriol)
The commonest blood test for vitamin D is a test for 25 hydroxyvitamin D. However, in some autoimmune conditions like Inflammatory Bowel Disease((6)) levels of 1,25 Dihydroxyvitamin D may rise without a concomitant rise in D3 levels.1,25 D levels may rise in other conditions like sarcoidosis and tuberculosis ((7)) as well. This may happen because of the production of calcitriol in tissues other than the kidneys.
In chronic kidney diseases ((8))levels of calcitriol may fall.
If you don’t have tuberculosis, sarcoidosis, chronic kidney disease or autoimmune diseases, it may not be necessary to measure 1,25 D levels. However, many of you take large doses of vitamin D3 supplements without measuring vitamin D levels in the blood. This may be dangerous!
What Is A Normal Vitamin D Level?
The only way to find out if you have vitamin D deficiency is by doing a blood test. There are no specific symptoms of low vitamin D. What are normal versus optimal levels of vitamin D? This is a question that can sometimes lead to excited (?heated) discussions. Several years ago the recommended levels were just enough to prevent rickets. But studies in recent years have shown that vitamin D is more than just bone and calcium metabolism. Ideally, every country should have recommended levels based on the local population, but in the absence of that, most countries follow the Endocrine Society guidelines((9)).
Vitamin D3 Levels | |
Deficiency | <20 ng/mL (<50 nmol/L) |
Insufficiency | 21-29 ng/mL (52-72 nmol/L). |
Optimal | 36-40 ng/mL (90-100 nmol/L) |
Toxicity | >150 ng/mL (374 nmol/L). |
In my practice in India very often I find patients with vitamin D3 levels in “single digits” (if they haven’t been supplementing regularly). Years ago I remember a patient had come to me with surprisingly normal levels of vitamin D3 who wasn’t taking any supplements. She was a farmer who spent about 8-9 hours in the sun on most days.
What Decides Your Vitamin D3 Levels?
Humans obtain vitamin D from either food (fortified), supplements or sunlight exposure. Your blood vitamin D levels depend on several factors.
1) Skin color:
People with dark skin ((10))require about 10 fold more exposure to sunlight to produce the same amount of vitamin D as people with lighter skin color.
2) Skin exposure:
The more exposed bare skin , the bigger the surface area of absorption of sunlight. Therefore if you are covered from head to toes and wear full-sleeved clothes, and the only area exposed is your face (which is not great for skin aging!), that is just 9-10% of your body surface area.
3)Air quality:
Excessive carbon particles in the air from the burning of fossil fuels may reduce the amount of vitamin D producing UVB rays from reaching your exposed skin.
4)Where Do You Live?
Your geographical location (latitude) determines how much UVB light you receive. The higher the angle at which the sun’s rays reach the earth’s surface like it is near the equator, the better it is for making vitamin D. Therefore if you live in the northern latitudes like in Canada and have darker skin, your natural ability to make vitamin D will be quite low.
5)Use of sunscreens:
Though theoretically use of sunscreens can block the UVB rays, rarely do people use adequate quantities of sunscreen to bar all UVB from reaching their skin. However, sensible sunlight exposure is important, particularly if you have a lighter skin color and are at high risk for skin cancer.
6)Liver and Kidney Health:
Some liver diseases may affect the metabolism of vitamin D3 by interfering with the conversion of cholecalciferol. (Fig 2). In chronic kidney disease (CKD) the vital step of conversion of vitamin D to its active form is affected and this can lead to severe vitamin D deficiency.
7)Gut Inflammation:
If you have inflammatory bowel conditions like Crohn’s disease or Ulcerative Colitis, you will absorb less vitamin D.
8)Medications:
Certain medications can affect your vitamin D levels. Some of the common ones are (Figure 1 above)
- Anti-seizure medications like Phenytoin, Carbamazepine.
- Glucocorticoids (Dexamethasone)
- Antibiotics like Clotrimazole, Rifampicin
- BP medications like Nifedipine, Spironolactone
- Herbals like St.John’s Wort.
- HIV drugs
9)Genetic Variations
If you have a genetic variation((11)) in Vitamin D Receptor or any of the D metabolizing enzymes, you may need a higher dose of vitamin D supplementation.
What About Vitamin D From Food?
Food is a poor source of vitamin D. In fact, food like milk does not naturally contain vitamin D. In an effort to prevent rickets several governments had started food fortification programs, where vitamin D was added to milk, juice, cereals (!), etc. Interestingly a certain cereal company (who shall not be named!) recently advertised that they were increasing the vitamin D content of their cereals. Seriously, are you looking at feeding your children with those processed sugary stuff to give them vitamin D?
The other food sources of vitamin D are non-vegetarian-mostly fish like salmon, mackerel, tuna, etc. Egg yolks contain some vitamin D but definitely not enough to maintain adequate blood levels.
How Much D3 Should You Take?
Ideally, you should aim for sensible sun exposure as well as supplementation with vitamin D3. Sun exposure has added benefits besides vitamin D((12)). Light exposure impacts the circadian clock, which in turn influences sleep, inflammation, mood, and metabolism.
What Decides How Much Vitamin D3 You Should Take?
The baseline concentration of vitamin D3 is the most important factor to decide how much you should take. This means you will not know if you do not measure.
What levels should you aim for?
You should aim for at least the optimal levels of 36-40 ng/mL (90-100 nmol/L) in blood.
Capsules, liquid or injections?
Capsules: Usually work well for most people.
Liquids: Perhaps better absorption and the convenience of dosage adjustments, particularly in countries where higher dosage vitamin D3 is only available as a prescription drug. Bear in mind: Please don’t mix in your smoothie. Liquid vitamin D3 is oily and may stick to the sides of the food processor jar and not get into you!
Injections: May be needed in those with gut absorption issues, but personally I do not routinely recommend injections since oral preparations give great results.
Dosage Of Vitamin D3
How much should you take? If you have extremely low blood levels (in”single digits”) then you will need higher doses for short intervals and then a lower maintenance dose ALWAYS!
Endocrine Society 2011 recommends((13))
……..all adults who are vitamin D deficient be treated with 50,000 IU of vitamin D2 or vitamin D3 once a week for 8 wk or its equivalent of 6000 IU/d of vitamin D2 or vitamin D3 to achieve a blood level of 25(OH)D above 30 ng/ml, followed by maintenance therapy of 1500–2000 IU/day
What Do I Recommend?
In India, D3 caps are commonly available as 60,000 IU and 2000 IU caps.
- If your vitamin D3 levels are extremely low, start with 60,000 IU once a week for 12 weeks.
- Measure your blood levels after 12 weeks of taking D3 at 60,000 IU weekly.
- If blood levels are 36-40 ng/mL (90-100 nmol/L), then continue at 4000-6000 IU /day ALWAYS! (Many of you stop your vitamin D3 after the first 12 weeks. Obviously your blood levels will not be maintained if you don’t take regularly!)
- If your blood levels have not reached the optimal levels after 12 weeks of high dose supplementation, then you may need to take it longer.
- Please do not take very high doses of vitamin D3 without measuring your blood levels. This case reported in a journal describes a 54-year-old man, who had kidney failure because of very high dose vitamin D3.((14))
On more detailed questioning, the patient mentioned that he was seeing a naturopathic specialist who had prescribed high doses of vitamin D, advising him to take 8 drops of a specific brand daily. The recommended brand contained 500 IU per drop. Unknowingly, the patient obtained another vitamin D preparation that contained 1000 IU per drop. The patient was not counselled about toxicity risks and, over a period of 2.5 years, he took 8–12 drops of vitamin D daily, for a total daily dose of 8000–12 000 IU.
Liquid preparations:
Most vitamin D3 liquids come as 1000 IU per drop. Therefore it is easy to take the required number of drops. 5 drops=5000 IU. Some of the liquid preparations come as a combination of vitamin D3 and K2, which is better for bone health.
When should you take D3 supplements?
Vitamin D3 can be taken at any time, on empty stomach or after meals. It does not necessarily need fat for absorption, but some practitioners recommend that you should take it with fatty food.
Daily, Weekly or Monthly?
In a study ((15)) from Belgium, where they compared supplementation of vitamin D 2000 IU vitamin D3 daily or 50,000 IU monthly in people with vitamin D deficiency.
The graph below shows the levels of the “other” vitamin D, the 1,25 dihydroxy vitamin D in the daily and monthly regimen. As you can see, the blue line represents the levels of 1,25 D after monthly high dose supplementation and the orange line represents the lower daily dose. The lower daily dose provides a more even level of 1,25 D than the high once a month dose. This is why I recommend a lower DAILY dose of D3.
The daily lower dose took about 2 weeks longer than the high monthly dose to reach their target level of 20 ng/mL.
How Often Should You Test Your Blood levels?
- Testing frequency will depend on your baseline levels.
- Ideally, repeat testing for vitamin D3 at least 12 weeks after supplementation.
- Once your blood levels have reached optimal levels, testing once a year is adequate, provided you have been supplementing at maintenance dose.
- You will need more frequent testing if you have mistakenly (or intentionally!) taken high dosages or your Parathyroid (PTH) hormone levels and or calcium and phosphate levels are abnormal.
Calcium supplementation and Vitamin D
Vitamin D (and magnesium) are extremely important for the absorption of calcium from the gut. ((16))Therefore, supplementing with only calcium in the presence of vitamin D deficiency will not give you optimal results. (How much calcium should you take will be discussed on another post).
Do People With Autoimmune Diseases Need More Vitamin D Supplementation?
There are many studies that have shown associations between vitamin D deficiency and chronic disease, but at present, there are no specific vitamin D targets ((17))for autoimmune diseases or recommendations for higher dosage in autoimmunity, hence we follow the best practices for good health.
Can I Take D3 Supplements Without Testing For D3?
While it is best to know your blood levels, you can supplement with lower doses of 2000-4000 IU/day without a high risk of causing D3 toxicity, but high daily doses are definitely not recommended without knowing your blood levels.
However, it is important to remember that if you are severely D3 deficient, a low daily dose may not help you reach optimal levels in a reasonable time.
Summary:
- Everyone needs vitamin D supplements AND sensible sunlight exposure.
- Sunlight exposure is more than maintaining vitamin D levels.
- Vitamin D affects the immune system function. Hence maintaining optimal blood levels are extremely important in autoimmunity.
- 1,25 D and autoimmunity, sarcoidosis, tuberculosis and kidney disease.
- Supplementation dosage, formulations.
- Monthly, weekly or daily dose.
- How often should you test?
- No place for daily high dose vitamin D without testing blood levels.