- Vitamin D2
- What is Vitamin D2?
- Important Information
- Before taking this medicine
- How should I take Vitamin D2?
- What happens if I miss a dose?
- What happens if I overdose?
- What should I avoid while taking Vitamin D2?
- Vitamin D2 side effects
- What other drugs will affect Vitamin D2?
- Further information
- More about Vitamin D2 (ergocalciferol)
- So why the confusion?
- What is the difference between vitamin D2 and vitamin D3?
- Is a prescription actually required to purchase vitamin D?
- What are vitamin D2 and vitamin D3 prescribed for?
- What else can you do to get more vitamin D?
- What is the recommended daily intake amount of vitamin D in general?
- Study Proves The Inadequacy Of Vitamin D2 (And The Superiority Of D3)
- So Why Are Most Prescription Supplements Vitamin D2?
- The Dangers Of Vitamin D Toxicity
- Why Vitamin D Matters For Your Bones
- What’s So Special About Vitamin K2?
- The Best Way To Get Vitamin D Is Through Sun Exposure
- The Amazing Effect of Vitamin D on Fall Prevention
- How Does Vitamin D Reduce Falls?
- What Kind of Vitamin D and How Much
- Already Taking Vitamin D? Here Are Other Easy Ways to Prevent Falls
- Vitamin D2 versus Vitamin D3
- Why is ergocalciferol prescribed?
- Surrogate versus Clinical Outcomes
Generic Name: ergocalciferol (vitamin D2) (ER goe kal SIF e role)
Brand Name: Calcidol, Calciferol, Drisdol, Vitamin D2
Medically reviewed by Drugs.com on Jul 16, 2018 – Written by Cerner Multum
- Side Effects
What is Vitamin D2?
Vitamin D2 is vitamin D2. Vitamin D helps your body absorb calcium.
Vitamin D2 is used to treat hypoparathyroidism (decreased functioning of the parathyroid glands).
Vitamin D2 is also used to treat rickets (softening of the bones caused by vitamin D deficiency) or low levels of phosphate in the blood (hypophosphatemia).
Vitamin D2 may also be used for purposes not listed in this medication guide.
You should not take Vitamin D2 if you have had an allergic reaction to vitamin D, or if you have high levels of calcium or vitamin D in your body, or any condition that makes it hard for your body to absorb nutrients from food (malabsorption).
Use only the recommended dose of ergocalciferol. An overdose could cause serious or life-threatening side effects.
Before taking this medicine
You should not take Vitamin D2 if you have had an allergic reaction to vitamin D, or if you have:
high levels of vitamin D in your body (hypervitaminosis D);
high levels of calcium in your blood (hypercalcemia); or
any condition that makes it hard for your body to absorb nutrients from food (malabsorption).
Tell your doctor if you have ever had:
kidney disease; or
an electrolyte imbalance.
Certain forms of ergocalciferol may contain ingredients you should know about, such as peanut or soybean oil, sugar, aspartame (phenylalanine), or certain food dyes. Ask a doctor before using Vitamin D2 if you have allergies, diabetes, or phenylketonuria (PKU).
Too much vitamin D could harm an unborn baby, and your dose needs may be different during pregnancy. Tell your doctor if you are pregnant or if you become pregnant while taking Vitamin D2.
Ergocalciferol can pass into breast milk and may cause side effects in the nursing baby. Tell your doctor if you are breast-feeding.
Do not give Vitamin D2 to a child without medical advice. Your child’s dose will depend on age, weight, diet, and other factors.
How should I take Vitamin D2?
Follow all directions on your prescription label and read all medication guides or instruction sheets. Use only the recommended dose of ergocalciferol.
It may be best to take Vitamin D2 after a meal, but you may take Vitamin D2 with or without food.
Measure liquid medicine carefully. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).
You will need frequent medical tests.
Your doctor may begin to reduce your Vitamin D2 dose as your condition improves. Carefully follow all instructions about adjusting your dose. In some cases, there may be a very small difference in amount between safe and dangerous doses of this medicine.
Your doctor will determine how long to treat you with this medicine.
Vitamin D2 may be only part of a complete program of treatment that also includes dietary changes and taking calcium and vitamin supplements. Follow your doctor’s instructions very closely.
Learn about the foods you should eat to make sure you get enough calcium and vitamin D in your diet. Your Vitamin D2 dose may need to be adjusted as you make changes to your diet.
Store at room temperature away from moisture, heat, and light.
What happens if I miss a dose?
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.
What happens if I overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of vitamin D can cause serious or life-threatening side effects.
Overdose symptoms may include nausea, loss of appetite, thirst, urinating more or less than usual, body aches, stiffness, confusion, or irregular heartbeats.
What should I avoid while taking Vitamin D2?
Ask a doctor or pharmacist before taking any multivitamins, mineral supplements, or antacids while you are taking Vitamin D2.
Vitamin D2 side effects
Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Stop taking Vitamin D2 and call your doctor at once if you have:
chest pain, feeling short of breath;
growth problems (in a child taking Vitamin D2); or
early signs of vitamin D overdose–weakness, metallic taste in your mouth, weight loss, muscle or bone pain, constipation, nausea, and vomiting.
Less serious side effects may be more likely, and you may have none at all.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What other drugs will affect Vitamin D2?
Certain medications can make it harder for your body to absorb vitamin D. If you take other medications, take them at least 2 hours before or 2 hours after you take Vitamin D2.
Tell your doctor about all your other medicines, especially:
a diuretic or “water pill”; or
mineral oil (sometimes taken as a laxative).
This list is not complete. Other drugs may affect Vitamin D2, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.
Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Copyright 1996-2018 Cerner Multum, Inc. Version: 5.02.
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More about Vitamin D2 (ergocalciferol)
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Other brands: Drisdol, Calciferol, Calcidol
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Related treatment guides
- Familial Hypophosphatemia
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Although these medications are both vitamin D supplements, they are available in different strengths and have different indications, as well as different potencies and absorption. The most common strength is the source of confusion though: both vitamin D2 and vitamin D3 come in a 50,000 unit capsule.
So why the confusion?
The trouble with vitamin D2 vs D3 comes up when your doctor does not specify on your prescription which type of vitamin D he or she wants you to have.
Many doctors will write vitamin D 50,000 units and leave it at that. The pharmacist will then have to call your doctor to find out their preference—D2 (ergocalciferol) or D3 (cholecalciferol).
What is the difference between vitamin D2 and vitamin D3?
At one time these two forms of vitamin D were thought to be equivalent, however, that is not the case! Vitamin D2 or ergocalciferol is actually less potent and has a shorter duration of action than its counterpart Vitamin D3 or cholecalciferol.
Is a prescription actually required to purchase vitamin D?
Vitamin D2 50,000 units requires a prescription, however, Vitamin D3 50,000 units does NOT require one.
However, although Vitamin D3 50,000 units does not require a prescription, it is still usually purchased from behind the pharmacy counter and may need to be ordered in.
What are vitamin D2 and vitamin D3 prescribed for?
Vitamin D2 is indicated for rickets, hypoparathyroidism, and familial hypophosphatemia. In contrast, vitamin D3 is indicated for dietary supplementation (use as a vitamin).
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What else can you do to get more vitamin D?
Vitamin D can be obtained from various sources including food, drink, and even sunlight. Some foods (such as tuna, salmon, sardines, egg yolks, mushrooms, and fortified cereal) and drinks (like milk, soy drinks, and orange juice) have up to 100 units of Vitamin D per serving.
What is the recommended daily intake amount of vitamin D in general?
The Institute of Medicine (IOM) recommends 600 units of Vitamin D per day for people 1 to 70 years of age, and 800 units of Vitamin D per day for those 71 years of age and older.
Asked by Jerri Koch
Are 50,000 International Units (IU) Of vitamin D Once A Week Harmful?
My doctor prescribed 50,000 IU of vitamin D, to be taken once a week due to vitamin D deficiency. Is this safe to take? Is there any way it would be toxic?
The dose that your physician prescribed is likely safe if used on a short-term basis. The Recommended Daily Allowance (RDA) for vitamin D is 600 IU for adults 18-70 years of age, and 800 IU for adults over 70. Vitamin D supplementation appears to be safe for adults when taken by mouth in doses of 4,000 IU daily (for a total of 28,000 IU per week).
When vitamin D deficiency is present, experts recommend a range of 40-2,000 IU of vitamin D each day depending on the severity of the deficiency. While the upper limit of this recommendation is 2,000 IU per day, research shows that high doses of vitamin D (10,000 to 50,000 IU daily) may be necessary for patients who have a history of malabsorption.
While vitamin D toxicity (also called hypervitaminosis D) is rare, it can have serious side effects. These include allergic skin reactions, a build-up of calcium in the arteries, headaches, muscle pain, kidney or urinary stones, and gastrointestinal problems (such as nausea, vomiting, constipation, and diarrhea).
Your vitamin D levels should be monitored closely during this time of high-dose supplementation. Report any adverse reactions to your doctor immediately.
You should know: The answer above provides general health information that is not intended to replace medical advice or treatment recommendations from a qualified healthcare professional.
See more helpful articles:
Facts About Vitamin D and Rheumatoid Arthritis
7 Ways to Get a Boost of Vitamin D
True or False: Get the Facts About Vitamin D
Hypersensitivity to vitamin D may be one etiologic factor in infants with idiopathic hypercalcemia. In these cases vitamin D must be strictly restricted.
Keep out of the reach of children.
Vitamin D administration from fortified foods, dietary supplements, self-administered and prescription drug sources should be evaluated. Therapeutic dosage should be readjusted as soon as there is clinical improvement. Dosage levels must be individualized and great care exercised to prevent serious toxic effects. IN VITAMIN D RESISTANT RICKETS THE RANGE BETWEEN THERAPEUTIC AND TOXIC DOSES IS NARROW. When high therapeutic doses are used progress should be followed with frequent blood calcium determinations.
In the treatment of hypoparathyroidism, intravenous calcium, parathyroid hormone, and/or dihydrotachysterol may be required.
Maintenance of a normal serum phosphorus level by dietary phosphate restriction and/or administration of aluminum gels as intestinal phosphate binders in those patients with hyperphosphatemia as frequently seen in renal osteodystrophy is essential to prevent metastatic calcification.
Adequate dietary calcium is necessary for clinical response to vitamin D therapy.
This product contains FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible individuals. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.
Protect from light.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term animal studies have been performed to evaluate the drug’s potential in these areas.
Pregnancy Category C
Animal reproduction studies have shown fetal abnormalities in several species associated with hypervitaminosis D. These are similar to the supravalvular aortic stenosis syndrome described in infants by Black in England (1963). This syndrome was characterized by supravalvular aortic stenosis, elfin facies, and mental retardation. For the protection of the fetus, therefore, the use of vitamin D in excess of the recommended dietary allowance during normal pregnancy should be avoided unless, in the judgment of the physician, potential benefits in a specific, unique case outweigh the significant hazards involved. The safety in excess of 400 IU of vitamin D daily during pregnancy has not been established.
Caution should be exercised when DRISDOL (ergocalciferol capsules) is administered to a nursing woman. In a mother given large doses of vitamin D, 25-hydroxycholecalciferol appeared in the milk and caused hypercalcemia in her child. Monitoring of the infant’s serum calcium concentration is required in that case (Goldberg, 1972).
Pediatric doses must be individualized (See DOSAGE AND ADMINISTRATION).
Clinical studies of DRISDOL (ergocalciferol capsules) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. A few published reports have suggested that the absorption of orally administered vitamin D may be attenuated in elderly compared to younger, individuals. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Today I am going to share with you some crucial but little-known information about Vitamin D that your doctor simply won’t tell you.
You see, if your blood test results have shown that you are Vitamin D deficient, chances are your doctor prescribed Vitamin D2 (ergocalciferol) supplements instead of D3 (cholecalciferol).
Today, you’ll learn the difference between these two forms of Vitamin D and why you should take D3 and never D2.
Study Proves The Inadequacy Of Vitamin D2 (And The Superiority Of D3)
A report published in The American Journal of Nutrition points out the very clear difference between Vitamin D3 and Vitamin D2, the latter, the “form of vitamin D used in major preparations of prescriptions in North America.”1 Vitamin D2 is in fact not the bioavailable equivalent of D3.
“Vitamin D2, if given in high enough doses, prevents infantile rickets and is capable of healing adult osteomalacia. However, the inefficiency of vitamin D2 compared with vitamin D3, on a per mole basis, at increasing 25(OH)D is now well documented, and no successful clinical trials to date have shown that vitamin D2 prevents fractures.”1(emphasis added)
The study goes on to state that
“… ergocalciferol should not be regarded as a nutrient suitable for supplementation or fortification.”1
Here’s why. There are several biological mechanisms that contribute to the superior absorbability and efficacy of Vitamin D3. In the liver, thanks to a particular hepatic enzyme, Vitamin D3 is more readily metabolized into a bioactive form of D that is easily converted to its hormone form in the kidneys. It takes much longer to make this hepatic conversion with Vitamin D2.1
In fact, D2 and D3 are metabolized so differently that they result in “the production of unique biologically active metabolites.”1
Clearly, these forms of Vitamin D are simply not the same. Hence the study’s conclusion that ergocalciferol should not be used as a supplement.
So Why Are Most Prescription Supplements Vitamin D2?
You may be wondering how Vitamin D2 supplements came to be the mainstream protocol in the first place. We need to go back almost 100 years to find the answer.
Back in the early 1920s, scientists discovered that exposing foods to ultraviolet light produced Vitamin D2. Thus the manufacture of this vitamin was born, and the process was sold to what would become Big Pharma. Drug companies then produced and sold this medicinal form of Vitamin D to the public and to doctors.
Less than 10 years later, around 1930, scientists noticed that Vitamin D2 did not seem as effective in the treatment of rickets in children (the primary use of the vitamin in those days) as the Vitamin D in cod liver oil.
Subsequent studies showed mixed results, and not surprisingly, in 1949 the World Health Organization declared that differences between the two forms are “minimal”. But recent research clearly shows that they could not be more wrong!
The Dangers Of Vitamin D Toxicity
One of the primary dangers of Vitamin D2 is that there is a fine line between an effective therapeutic dose and toxicity. In fact, prescription Vitamin D2 carries a warning that the dosage should be adjusted as soon as there is notable improvement in D levels.
The popular prescription Vitamin D2, Drisdol, carries the following warning (among others):
“Dosage levels must be individualized and great care exercised to prevent serious toxic effects. IN VITAMIN D RESISTANT RICKETS THE RANGE BETWEEN THERAPEUTIC AND TOXIC DOSES IS NARROW.”2
Why risk poisoning when there is a completely safe way to get all the Vitamin D3 (not D2) you need? We’re going to discuss that in a moment, but first I would like to briefly review…
Why Vitamin D Matters For Your Bones
It’s well-documented that Vitamin D is essential for the proper synthesis of calcium, and it’s been shown to greatly reduce fracture risk in two ways. First, it helps with the formation of stronger bones; second, Vitamin D actually helps improve balance and prevent falls by enhancing muscle contraction.
For rejuvenating your bones, it’s vitally important that you avoid Vitamin D2, and choose a bioavailable form of this important vitamin to avoid deficiency.
If you live in an area where it’s difficult to get sun exposure or if you can’t spend 20 to 30 minutes outdoors a few times a week, I recommend taking 8,000-10,000 IU once every 3rd day Via transdermal patch. Don’t worry that you may have too much Vitamin D if you also sunbathe. Remember that there’s no risk of overdosing from the sun.
What’s So Special About Vitamin K2?
Vitamin K is actually a group of fat-soluble vitamins. Of the two main ones, K1 and K2, the one receiving the most attention is K1, which is found in green leafy vegetables and is very easy to get through your diet. This lack of distinction has created a lot of confusion, and it’s one of the reasons why vitamin K2 has been overlooked for so long. The three types of vitamin K are:
- Vitamin K1, or phylloquinone, is found naturally in plants, especially green vegetables; K1 goes directly to your liver and helps you maintain healthy blood clotting
- Vitamin K2, also called menaquinone, is made by the bacteria that line your gastrointestinal tract; K2 goes straight to your blood vessel walls, bones, and tissues other than your liver
- Vitamin K3, or menadione, is a synthetic form I do not recommend; it’s important to note that toxicity has occurred in infants injected with this synthetic vitamin K3
It also plays a role in removing calcium from areas where it shouldn’t be, such as in your arteries and soft tissues. “K2 is really critical for keeping your bones strong and your arteries clear,” Rheaume-Bleue says.
Now, vitamin K2 can be broken into two additional categories, called:
- MK-4 (menaquinone-4), a short-chain form of vitamin K2 found in butter, egg yolks, and animal-based foods
- MK-7 (menaquinone-7), longer-chain forms found in fermented foods. There’s a variety of these long-chain forms but the most common one is MK-7. This is the one you’ll want to look for in supplements, because in a supplement form, the MK-4 products are actually synthetic. They are not derived from natural food products containing MK-4.Vitamin K1 exclusively participates in blood clotting — that’s sole purpose. K2 on the other hand comes from a whole different set of food sources, and its biological role is to help move calcium into the proper areas in your body, such as your bones and teeth.
- The MK-7 – these long-chain, natural bacterial-derived vitamin K2 – is from a fermentation process, which offers a number of health advantages:
- It stays in your body longer, and
- It has a longer half-life, which means you can just take it once a day in very convenient dosing
- This formula has D3, K2, calcium, and other vital minerals for promoting osteoblast Bone healthy Vitamin D3 formula
The Best Way To Get Vitamin D Is Through Sun Exposure
You can’t beat sunlight for the optimal form and dosage of Vitamin D. As I mentioned earlier, you can’t possibly “overdose” into Vitamin D toxicity, because your body naturally cuts off its manufacture when you’ve made what your body needs (even if you are still out in the sun).
Of course, while Vitamin D toxicity is impossible through sun exposure, you do have to be careful to avoid getting burned.
The Amazing Effect of Vitamin D on Fall Prevention
Preventing falls is fundamental to reducing the incidence of fracture. That is why the Save Our Bones™ lifestyle includes exercises that improve balance. And as it turns out, Vitamin D plays a more active role in this process than we have ever realized.
Researchers at Harvard Medical School reviewed a number of studies that explored Vitamin D’s contribution to fall prevention which revealed amazing findings. “Vitamin D supplementation appears to reduce the risk of falls among ambulatory or institutionalized older individuals with stable health by more than 20%1,” the study concludes.
How Does Vitamin D Reduce Falls?
The mechanism by which Vitamin D does this has to do with how it’s metabolized in the body. One of the byproducts of Vitamin D’s breakdown, called 1,25-hydroxyvitamin D, actually enters muscle cells and affects the nucleus. Once there, 1,25-hydroxyvitamin D enhances the cell’s contraction ability.
Muscles work by contraction and relaxation. A muscle’s ability to contract is essential to its strength and response to outside forces. Vitamin D, then, makes muscles stronger in a very direct way.
What Kind of Vitamin D and How Much
When it comes to Vitamin D supplements, D3 obtained via transdermal vitamin patch delivers higher efficacy.
My recommendation is to get as much Vitamin D as you can from sunlight. It’s impossible to overdose on Vitamin D obtained from the sun. If you live in an area with little sunshine, you need to use supplements to make sure you have adequate levels of this crucial
Already Taking Vitamin D? Here Are Other Easy Ways to Prevent Falls
What this meta-analysis also shows is the importance of strong muscles in decreasing your chance of falling. Vitamin D clearly helps with muscle strengthening, but so does exercise.
Core-strengthening exercises are particularly helpful in fall prevention, because the abdominal muscles help hold you steady and upright. In fact, core muscles affect nearly every movement. No matter what activity you’re doing, your motions originate from and/or move through your core. Even sitting up straight engages these central muscles, as do standing, turning, and twisting. Weakened core muscles can result in back pain and poor balance that can lead to falls.
Bone healthy Vitamin D3 formula
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Supplementation with large doses of vitamin D2 or D3 forms boosted blood levels of the vitamin (as measured by 25(OH)D levels), but declines in 25(OH)D were more rapid in the D2 group, compared with the D3 group, report scientists from the Hospital de Clinicas in Buenos Aires and the Universidad de Buenos in Buenos Aires
Fifty days after the last dose of vitamin D, the D2 group’s 25(OH)D levels were the same as those in the placebo group, but elevated levels were still observed in the D3 group, according to findings published in the European Journal of Clinical Nutrition.
“In the long term, vitamin D3 seems more appropriate to sustain adequate levels of 25OHD, which could be relevant for classic and non-classic effects of vitamin D,” wrote the researchers.
The sunshine vitamin
According to the 2014 CRN Consumer Survey on Dietary Supplements, vitamin D is the second leading category among supplement users after multivitamins.
Vitamin D refers to two biologically inactive precursors – D3, also known as cholecalciferol, and D2, also known as ergocalciferol. Both D3 and D2 precursors are transformed in the liver and kidneys into 25- hydroxyvitamin D (25(OH)D), the non-active ‘storage’ form, and 1,25-dihydroxyvitamin D (1,25(OH)2D).
Vitamin D deficiency in adults is reported to precipitate or exacerbate osteopenia, osteoporosis, muscle weakness, fractures, common cancers, autoimmune diseases, infectious diseases and cardiovascular diseases. There is also some evidence that the vitamin may reduce the incidence of several types of cancer and type-1 and -2 diabetes.
While our bodies do manufacture vitamin D on exposure to sunshine, the levels in some northern countries are so weak during the winter months that our body makes no vitamin D at all, meaning that dietary supplements and fortified foods are seen by many as the best way to boost intakes of vitamin D.
D2 vs D3
Several studies have reported that the D3 form of the vitamin is more potent that D2, with a study led by Robert Heaney, MD, from Creighton University in Nebraska reporting earlier this year that D3 was 87% more potent than D2 (Journal of Clinical Endocrinology & Metabolism, doi: 10.1210/jc.2010-2230).
However, a study led by Michael Holick, PhD, MD, from Boston University and published in the American Journal of Clinical Nutrition indicated that fortification of orange juice with either vitamin D2 or D3 produces the same increases in blood levels as consuming either vitamin via capsules.
A 2012 analysis of data from seven randomized controlled trials published in the American Journal of Clinical Nutrition indicated that the majority of the evidence supports the hypothesis that D3 is more effective than D2.
“A central point for framing the discussion about the best supplementation is the understanding about the continuous or discontinuous need of some level of vitamin D in blood,” explained the Buenos Aires-based scientists. “In addition to the well-known effect on bone, vitamin D possesses pleiotropic actions on the immune and endocrine systems, and on common cell functions, such as proliferation and differentiation.
“Most of these non-classic effects depend upon the tissue-specific regulation of 1,25(OH)2D, which requires adequate blood levels of 25OHD as substrate, suggesting that prolonged or continuous level of 25OHD could be worthwhile.”
Led by Beatriz Oliveri, the researchers recruited 33 healthy people with an average age of 33 and divided them into three groups: One group was placebo, and the other two received a starting dose of 100,000 IU of either vitamin D2 or D3. One week later they were then given 4,800 IU per day of the same D form for a further two weeks. The participants were monitored for a total of 11 weeks.
Results showed that the starting dose of D2 and D3 boosted 25OHD levels to similar levels. The area under the curve for 25(OH)D was 28.6% higher for D3 compared with D2 between day 7 and day 77, said the researchers.
“fter a period with the same daily doses of vitamin D2 and D3, the 25OHD levels in the group that received vitamin D2 declined faster than the levels in the vitamin D3 group, reaching similar levels as the placebo group at the final point,” they wrote.
“A different AUC among vitamin D-supplemented subjects could be clinically relevant if adequate levels of 25OHD were continuously required. If this were the case, vitamin D3 use could be a better option. The rationale for a need of continuous 25OHD is currently insufficient, although some evidence suggests that such levels are worthwhile, in particular for non-classic vitamin D effects, which seem mediated via localized autocrine or paracrine synthesis of 1,25(OH)2D depending on the adequacy of 25OHD levels.”
In the United States, vitamin D supplementation is primarily available as vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Although these two have historically been considered interchangeable and equipotent, the current body of literature strongly supports the preference of Vitamin D3 (cholecalciferol) over D2 (ergocalciferol).
Vitamin D2 versus Vitamin D3
Vitamin D3 (cholecalciferol) is produced by the human body in response to sunlight and is also available through dietary sources, such as fish. In contrast, vitamin D2 (ergocalciferol) is not produced in the human body, but is created by exposing certain plant-derived materials to ultraviolet light.
When the manufacturing method for ergocalciferol was created, binding studies of the vitamin D receptor in rats showed equipotency between ergocalciferol and cholecalciferol. On the basis of this animal data, most resources cite the two being equipotent and interchangeable.
Given that both ergocalciferol and cholecalciferol undergo metabolic changes in the human body, which differ from other animals, it should make sense that a binding study in rats may not be sufficient to show equivalence. In fact, recent literature (Trang 1998, Armas 2004, Houghton 2006) convincingly demonstrates that cholecalciferol is 1.7 to 3 times more potent and has a longer-lasting effect than ergocalciferol in increasing serum 25-hydroxyvitamin D levels, the active form of vitamin D in humans. The difference in duration of effect and potency are well demonstrated in a study by Armas et al:
Healthy volunteers were given a single 50,000 unit dose of either vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol)
Why is ergocalciferol prescribed?
If ergocalciferol is less potent and has a shorter duration of effect, why is it used? The most likely reason is due to dosage formulations. Unlike cholecalciferol, which is typically only available as a maximum dose of 5,000 units per capsule or tablet, ergocalciferol is available as a monster 50,000 unit dose. This larger dose may be seen as more convenient for patients or healthcare providers who want to provide supplementation on a weekly or monthly basis.
Surrogate versus Clinical Outcomes
Although 25-hydroxyvitamin D levels are a better surrogate than a rat binding study, clinical outcomes are the most relevant. Low levels of 25-hydroxyvitamin D (less than 20 ng/mL; Bjelakovic 2014) are very common in North America and have been associated with a wide variety of diseases including osteoporosis, bone fractures, malignancy, cardiovascular disease, infections, and more. The majority of the data supports association, not causation, of low vitamin D levels. In other words, much of the data does not clearly support the idea that vitamin D supplementation in a patient with low vitamin D levels reduces the risk of these diseases.
With that said, a recent Cochrane review (Bjelakovic 2014) analyzed the all-cause mortality benefit of vitamin D supplementation (both D2 and D3) by pooling 95,286 participants from 56 randomized clinical trials. In this meta-analysis, about 80% of participants received cholecalciferol (median dose 800 units/day) and about 20% received ergocalciferol (median 1000 units/day). The vast majority were women (77%), and most were older than 70 years of age.
The Cochrane review calculated an all-cause mortality relative risk (RR) of 0.97 (95% CI 0.94-0.99, p=0.02), which represented a raw difference in mortality of 12.5% (control) vs. 12.7% (vitamin D). The authors calculated a number needed to treat (NNT) of 150 over five years; however, the NNT calculates to 500 over a weighted mean of 4.4 years using the raw difference in mortality rates. Importantly, the difference in mortality was only demonstrated for trials examining cholecalciferol. Although ergocalciferol did make up a minority of the meta-analysis, it was adequately powered to detect a 5% difference in relative risk reduction.
- Cholecalciferol (vitamin D3) is more potent and longer acting than ergocalciferol (vitamin D2) as measured by the active form of vitamin D in the blood (25-hydroxyvitamin D).
- Low vitamin D levels are common in North America; most data supports an association between low vitamin D levels and disease. Much less data supports a cause-and-effect relationship between vitamin D supplementation and prevention of specific diseases.
- Vitamin D supplementation with cholecalciferol (D3) appears to have a small but statistically significant benefit in improving all-cause mortality among elderly women. The mortality benefit in younger patients or male patients is not clear.
- Ergocalciferol (D2) is less studied than cholecalciferol and was not shown to confer a mortality benefit in a recent Cochrane meta-analysis despite adequate statistical power.
- For patients who meet criteria for vitamin D supplementation (which is an entire argument in itself), vitamin D3 (cholecalciferol) should be selected over vitamin D2 (ergocalciferol).
- Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metab. 2004 Nov;89(11):5387-91. PMID 15531486.
- Trang HM, Cole DE, Rubin LA, et al. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr. 1998 Oct;68(4):854-8. PMID 9771862
- Houghton LA, Vieth R. The case against ergocalciferol (vitamin D2) as a vitamin supplement. Am J Clin Nutr. 2006 Oct;84(4):694-7. PMID 17023693.
- Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2014 Jan 10;1:CD007470. PMID 24414552.
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