What is vitamin D₃?

Vitamin D₃, also known as cholecalciferol or colecalciferol, is the substrate (the raw material) for the steroid hormone, 1,25(OH)₂D₃, also known as calcitriol, involved in many vital functions in most cells of the body. Vitamin D₃ is formed in the skin under the influence of UVB in sun- or artificial UVB light. Only a few foods contain some vitamin D₃.

Why is vitamin D₃ important?

Vitamin D is required for optimal bone, muscle and nerve health, and appears to have a wide range of other important functions in the body. A low serum vitamin D level may be associated with several (autoimmune) diseases including MS.
Source: Van der Mei IA. Information on Vitamin D levels for People with Multiple Sclerosis. Menzies Research Institute, 2007.

Vitamin D is required for optimal bone health, and vitamin D deficiency can lead to osteoporosis and influence neuromuscular function (strength and balance). This can result in falls and ultimately, fractures. Interestingly, recent literature has suggested that vitamin D deficiency might also be associated with the onset of diseases such as multiple sclerosis (MS), diabetes, colorectal cancer, breast cancer, prostate cancer, cardiovascular diseases, periodontal disease and tuberculosis, as well as propensity to falls, chronic pain, all of which indicates that ultraviolet radiation or vitamin D does much more in the body than maintain optimal bone health.
Source: Van der Mei IA. Information on Vitamin D levels for People with Multiple Sclerosis. Menzies Research Institute, 2007.

Which symptoms of MS might be alleviated by vitamin D₃?

What is the cause of Multiple Sclerosis (MS)?

Multiple sclerosis (MS) is a neurodegenerative disease of uncertain etiology. In MS, neurodegeneration is thought to be secondary to autoimmune-mediated damage. However, no cohesive explanation yet exists as to how environmental factors interact to induce a neurodegenerative autoimmune response. Insufficient sunlight exposure and chronic viral infections have been proposed as unrelated environmental risk factors for MS. Colleen Hayes and Donald Achaeson suggest that these risk factors may act synergistically to enable the pathogenic autoimmune response. Low ultraviolet light (UVL) exposure depletes vitamin D3 stores, and low vitamin D3 levels correlate strongly with high MS risk. The central nervous system converts vitamin D3 into 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), a biologically active hormone with antiinflammatory and neuro-protective functions that depend on IL-10-producing regulatory lymphocytes. Herpesvirus infection also correlates with MS risk. Some herpesviruses like Epstein-Barr virus produce an IL-10-like cytokine termed vIL-10. Colleen Hayes and Donald Achaeson hypothesize that vIL-10 may induce a dysfunction of IL-10-producing regulatory lymphocytes, thereby undermining the protective functions of sunlight, vitamin D3, and 1,25-(OH)2D3. The vIL-10 could elicit a host immune response capable of neutralizing or depleting IL-10, or the vIL-10 could compete with IL-10 but fail to perform an essential IL-10 function. In either case, the lack of sunlight exposure and the herpes virus infection might synergize to induce a defect in IL-10-producing regulatory lymphocyte function that undermines self-tolerance mechanisms and enables a pathogenic autoimmune response to neural proteins.
Source: Hayes CE, Donald Acheson E. A unifying multiple sclerosis etiology linking virus infection, sunlight, and vitamin D, through viral interleukin-10. Med Hypotheses. 2008;71(1):85-90. Epub 2008 Apr 2.

What does vitamin D deficient mean?

The definition of vitamin D deficient is changing as research is showing that the 25(OH)D concentration in blood for optimal health is higher than were previously thought.

The cut-off point for vitamin D deficiency is 50 nmol/L, in other words people with a vitamin D level of 50 nmol/L or less are considered vitamin D deficient. People with a vitamin D level above 50 nmol/L are considered vitamin D sufficient. However, controversy exists over what cut-off should be recommended.

In Tasmania at latitude 41°-43° S, the risk of becoming vitamin D deficient is particularly high in winter and spring. Among people with MS: those more disabled (EDSS > 3) are more often vitamin D deficient all year round and spend less time outside compared to those who are more ambulant. Indeed, the more disabled people with MS were three times more likely to be vitamin D deficient compared to healthy people without MS. There was no difference between the more ambulant people with MS and people without MS. Thus it seems that more disabled people with MS may spend less time outside and therefore have deficient vitamin D levels. Importantly, the more ambulant people with MS were as likely as the healthy people without MS to have vitamin D deficiency, indicating that this is also a concern among the general population.

What does vitamin D level mean?

The vitamin D level is the concentration of 25(OH)D in your blood. The serum 25(OH)D concentration is accepted as the nutritional biomarker of vitamin D sufficiency. Vitamin D levels are higher in summer/autumn, and lower in winter/spring. The vitamin D level reflects both sun exposure and vitamin D intake. It is the marker of vitamin D availability to tissues, including the immune system. Vitamin D levels are lower in people with disability e.g. caused by MS.

How high is my vitamin D level?

Individuals vary in their vitamin D levels and in their response to efforts to increase these levels.

A simple blood test can determine your current vitamin D level. To check your vitamin D level, ask your health care provider for a 25(OH)D blood test. Your health care provider can then advise you on whether you need to increase your vitamin D level.
Source: Van der Mei IA. Information on Vitamin D levels for People with Multiple Sclerosis. Menzies Research Institute, 2007.

How high should my vitamin D level be?

The recommended minimum vitamin D level is at least 50 nmol/L, but recent research suggests there may be additional benefit in maintaining vitamin D levels of 75, 100 and 125 nmol/L or higher.
Source: Van der Mei IA. Information on Vitamin D levels for People with Multiple Sclerosis. Menzies Research Institute, 2007.

Or between 100 - 150 nmol/L.
Source: Scientists' Call to D*Action

The average 25(OH)D concentration of the confirmed cases of vitamin D toxicity was 535 nmol/L (214 ng/ml).
Source: Vieth R. Vitamin D toxicity, policy, and science. J Bone Miner Res. 2007 Dec;22 Suppl 2:V64-8. Review.

How do I increase my vitamin D level?

There are a few ways to increase vitamin D levels. It also depends on where you live.

In summer

• Increase exposure to sunlight;

In winter
At latitudes greater than 35° where sunlight is not strong enough in winter to make enough vitamin D₃ in the skin.

• Increase the intake of foods containing vitamin D₃ or

• Take vitamin D supplements or

• Use artificial UVB light.

Can I combine sunlight exposure and vitamin D intake to increase my vitamin D level?

To achieve an optimal vitamin D level, it is advisable to combine sunlight exposure and vitamin D intake. Here is an example for people with MS who are ambulant or who are disabled.

The ambulant (low disability) group had no disability or could walk an unlimited distance without rest but not run.

Table 1.
Recommendations for Tasmanians with Multiple Sclerosis to prevent vitamin D deficiency.

Source: Van der Mei IA. Information on Vitamin D levels for People with Multiple Sclerosis. Menzies Research Institute, 2007.

How long will it take to increase my vitamin D level?

On average it takes sunlight 2 months to optimise vitamin D levels after winter to summer levels.
Source: VanAmerongen BM, Dijkstra CD, Lips P, Polman CH.Multiple sclerosis and vitamin D: an update.Eur J Clin Nutr. 2004 Aug;58(8):1095-109.

To optimize vitamin D levels to more than 100 nmol/L depends on on baseline serum 25(OH)D, exposure to sunshine and your vitamin D₃ intake. Therefore it is advisable to monitor your vitamin D level. Choice of a larger dose may be based on the wintertime serum 25(OH)D level.

How do I know if sunlight is strong enough to make vitamin D in my skin?

• When you stand in the sun and you cast a shorter shadow or

• Use a website that can calculate how long you need to sit in the sun:

Duration of Vitamin D Synthesis in Human Skin (accessed May 2008).

What is the safe amount of exposure to sunlight?

Exposure to the sun is the cheapest way to increase vitamin D levels, but could come at a cost because it increases the risk of skin cancer and eye disease.
Source: Van der Mei IA. Information on Vitamin D levels for People with Multiple Sclerosis. Menzies Research Institute, 2007.

Please, take into account the WHO sun protection recommendations for skin cancer prevention (accessed May 2008).

Table 2.
WHO sun protection recommendations for skin cancer prevention.4

What to do if the heat of the sun makes my MS symptoms worse?

The heat of the sun might make your MS symptoms worse. If so, don’t stay out in the direct sun for more than 10-15 minutes, or try to avoid the direct heat of the sun by only going outside when there is a pleasant breeze. Alternatively sit in the shade of a tree for 20-30 minutes.

How much skin should I expose to sunlight?

Expose as much skin as possible. Vitamin D is produced in the body when the skin is exposed to sunlight. Therefore, wearing a lot of clothing, like we do in winter, will limit the amount of vitamin D we produce.

How long should I stay in the sun?

Avoid excessive sun exposure at all times, including getting sunburnt, as this is a known risk factor for skin cancer, especially melanoma. The risk of sunburn is highest in summer.
Please, take into account the WHO sun protection recommendations for skin cancer prevention (accessed May 2008).
Short exposures 10-15 minutes may be more efficient at producing vitamin D₃ as continued exposure to UVB results in degradation of vitamin D₃.

When should I apply sunscreen?

Does it matter at what time of day I am out in the sun?

The amount of vitamin D₃ produced under the influence of the sun depends on the strength of the sun. The strength of the sun varies throughout the year (highest in summer and lowest in winter). It also varies during the day (lower in the morning and late afternoon, higher during the middle of the day). There is a certain threshold below which the body cannot produce any vitamin D₃. In Tasmania, people are still able to generate some vitamin D₃ in winter but it is less than in summer. Also, being outside early in the morning or late in the afternoon during the winter has little effect on your vitamin D levels.

Do people with a darker skin need more sun?

People with darker skin require more sun to produce the same amount of vitamin D₃ compared to people with lighter skin.

Do vitamin D₃ levels increase sitting behind a window?

Glass filters nearly all ultraviolet radiation rays that are required to produce vitamin D₃ in the skin. Therefore, vitamin D levels do not increase if sitting behind a window.

How do I increase my vitamin D level through dietary intake of food?

Less than 5% of the vitamin D in our body comes from dietary sources. The best source is fatty fish, such as mackerel, herring and wild salmon. Liver, eggs and fortified foods, such as margarine (3 IU/g (0,075 μg/g)) and some milk, also contain a very small amount of vitamin D₃. For most people, unless you are an Eskimo eating cod liver oil and fish, adequate vitamin D levels are unlikely to be achieved through diet alone.

How much vitamin D₃ should I take??

Recent studies suggest that the current RDA/DV of vitamin D - 200 IU (5 μg) for individuals under age 50, 400 IU (10 μg) for those between the ages of 50 and 70, and 600 IU (15 μg) for those over the age of 70 - may not be adequate.

Vitamin D level
Vitamin D sufficiency is currently defined as a blood test level above 50 nmol/L. However, the optimal vitamin D level is unknown and threshold values of 75 nmol/L, 100 nmol/L or 125 nml/L have been suggested.

Vitamin D intake
Take a vitamin D supplement of at least 1000 IU (25 μg) per day.There is general consensus among scientists that vitamin D intake required to prevent vitamin D levels below 50 nmol/L should be at least 1000 IU (25 μg) per day.2 This intake is also recommended by the Canadian Cancer Society. Taking 1000 IU (25 μg) per day seems to increase vitamin D levels on average to about 70 nmol/L.

• If your vitamin D level is deficient, the treatment has to be aimed at repleting your vitamin D level to above 50 nmol/L.
• If your vitamin D level is sufficient, the treatment has to be aimed at maintaining that vitamin D level all year round.

• 3000-5000 IU (75 μg – 125 μg) vitamin D₃ (cholecalciferol) per day (3-5 capsules of 1000 IU (25 μg) vitamin D₃ (cholecalciferol) per day) for 6-12 weeks, after which e.g. 1000 IU per day can be used or
• 50 000 IU (1.25 mg) vitamin D₃ (cholecalciferol) per month (1 capsule of 50 000 IU (1.25 mg) vitamin D₃ (cholecalciferol) per month) for 3-6 months, after which e.g. 1000 IU per day can be used or
• a single dose of up to 500 000 IU (12.5 mg) vitamin D₃ (cholecalciferol) (10 capsules of 50 000 IU (1.25 mg), after which e.g. 1000 IU per day can be used.

Ask your health care provider to monitor your vitamin D levels twice a year, as long as they are deficient. Preferably at the end of winter when vitamin D levels are at their lowest and at the end of summer when they are at their highest. Continue to monitor twice a year until your level is sufficient (at least 50 nmol/L) in winter.As soon as your vitamin D level is sufficient a supplement with 1000 IU (25 μg or 0,025 mg) vitamin D₃ (cholecalciferol) per day can be used.

Recommendations for maintaining vitamin D sufficiency
The following vitamin D intake is recommended to maintain your vitamin D level above 50 nmol/L:
There is general consensus among scientists that vitamin D intake required to prevent vitamin D levels below 50 nmol/L should be at least 1000 IU (25 μg) per day.2
This intake is also recommended by the Canadian Cancer Society.

• 1000 IU (25 μg) per day increases vitamin D levels on average to about 70 nmol/L.
• 2000 IU (50 μg) per day increases vitamin D levels on average to about 90 nmol/L.
• 4000 IU (100 μg) per day increases vitamin D levels on average to about 100/112 nmol/L.3 vieth

Ask your health care provider to monitor your vitamin D levels once a year: at the end of winter when it is at its lowest level. Ajust your doses until your level is at the desired level.
No adverse effects have been reported at these doses.
Source: Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr 2001;73(2):288-94.

When should I ask my health care provider for a vitamin D blood test?

The risk of being vitamin D deficient is generally higher when living further away from the equator and lower when living closer to the equator because of differences in strength of the sun. However, behaviour such as the amount of time spent outside, the time of day being outside, the amount of clothing worn and the use of sunscreen are also important determinants of your level of vitamin D. A blood test, performed by your health care provider, is the best method to determine whether there is a need to increase your vitamin D levels.

Do I need to inform my health care provider that I’m taking vitamin D supplements?

If you decide to take more than 2000 IU (50 μg) vitamin D supplements per day, it is suggested that you inform your health professional.

What are the side effects of vitamin D₃?

Excessive intakes of vitamin D are evident by hypercalcaemia, dehydration and tissuecalcification.1–3 hypercalcaemia hypercalcuria vieth

Isn’t vitamin D toxic?

The threshold vitamin D level for vitamin D toxicity has not been established. There is no evidence that toxicity occurs at levels below 600 nmol/L (240 ng/ml) or with daily oral consumption of 250 μg (10 000 IU)/d vitamin D₃.

Vitamin D causes hypercalcemia when the "free" concentration of 1,25(OH)₂D is inappropriately high. Adminitration of 1,25(OH)₂D may cause coronary and valvular calcification.

Hyper calcemia is the key criterion for vitamin D toxicity. A measure of an impeding adverse response, capable of detecting modest excess in vitamin D, is hypercalciuria. This can be monitored easily by measuring the ratio of calcium to creatinine in a random morning urine sample. Hypercalciuria has been defined as urine calcium/creatinine >1 mmol/mmol (>0.37 mg/mg).
Source: Vieth R. Vitamin D toxicity, policy, and science. J Bone Miner Res. 2007 Dec;22 Suppl 2:V64-8. Review.

Where can I buy vitamin D₃ supplements?

Vitamin D comes in two forms; D₃ and D₂. Buy vitamin D₃, since this form works better for most people. If the product doesn’t say D₃ on the front label, look for the name “cholecalciferol” in the list of ingredients on the back of the bottle – that’s another name for D₃.

Vitamin D₃ supplements currently available in

AUSTRALIA
There are three over-the-counter pure vitamin D preparations available in Australia, OsteVit-D, Ostelin Vitamin D and Blackmores vitamin D₃. Each capsule contains 1000 international units (IU). OsteVit-D and Blackmores both contain vitamin D₃ (cholecalciferol). Ostelin contains vitamin D₂ (ergocalciferol). People do not produce vitamin D₂ naturally in the body and vitamin D₂ seems a little less effective in raising vitamin D levels than vitamin D₃. OsteVit-D is the least expensive, retailing for around $32 for 250 capsules. Alternatively, a high dose preparation of vitamin D₃ (50,000 IU per capsule, taken monthly, around $60 for 12 capsules) can be ordered at Chemist Warehouse (144 Murray St, Hobart) with a prescription from a specialist physician, geriatrician, endocrinologist or rheumatologist.

- Netherlands
Vitamine D KIND - Kruidvat
Devaron® (zelfzorg) Tablet: 400 IE colecalciferol (vitamine D₃)
http://www.consumed.nl/medicijnen/774/Devaron%C2%AE_zelfzorg
Niet gebruiken bij (= contra-indicaties) o.a.
o Calcium-gehalte van het bloed, verhoogd (= hypercalciëmie)
o Nierstenen (tenzij de arts anders voorschrijft)

Colecalciferol (recept)

What is the difference between vitamin D₃ and vitamin D₂?

• Cholecalciferol (vitamin D₃), formed in the skin through the action of ultraviolet (UV) light on 7-dehydrocholesterol to produce cholecalciferol.• Ergocalciferol (vitamin D₂), produced by UV irradiation of the plant steroid ergosterol.

What is the difference between vitamin D₃ and 1,25-(OH)₂D₃?

Serum 1,25(OH)₂D₃ levels play no roll in diagnosing vitamin D deficiency. Serum 1,25(OH)₂D₃ levels are tightly controlled. They are often normal or even elevated in vitamin D deficiency. Therefore, a patient with normal or high 1,25(OH)₂D₃ serum levels but low 25(OH)D levels is vitamin D deficient despite high serum levels of the active hormone. Calcitriol (1,25-(OH)₂D₃) is not appropriate for treating patients with deprivational vitamin D deficiency as it has a narrow therapeutic window, may result in hypercalcaemia or hypercalciuria and does not increase serum 25-OHD levels.

What does IU stand for?

International Units (IU) 1000 IU equals 0.025 mg or 25 microgram (μg or mcg or mug). In the new official units for vitamins, 1000 IU/d translates to 25 ug/day

What does μg or mcg or mug stand for?

1 microgram (μg or mcg or mug) equals 40 International Units (IU).

What does nmol/L stand for?

Vitamin D levels are reported in either ng/mL or nmol/L.
1.0 nmol/L equals 0.4 ng/mL.