Vitamin D Toxicity
Every article written in newspapers and magazines about vitamin D always includes an overly scary caution about vitamin D toxicity. The reader gets the impression that it must be a common consequence of vitamin D supplementation. Some readers get so scared, they decide not to take vitamin D supplementation and end up with the health consequences of vitamin D deficiency. What a shame! It’s obvious to me that the writers of these magazine and newspaper articles don’t actually treat patients with low vitamin D and their knowledge about vitamin D toxicity is very limited and superficial.
What Is Vitamin D Toxicity?
Vitamin D toxicity is defined as “too much vitamin D, causing harm to the body.”
What Level Of Vitamin D Causes Damage To The Body?
According to an excellent review article (1) from Queen’s University in Kingston, Canada, the author concluded that a blood level of 25 (OH) vitamin D more than 300 ng/ml (750 nmol/L) is considered to cause toxicity. In an animal model (2), blood concentration of vitamin D up to 400 ng/ml (1000 nmol/L) was not associated with any toxicity.
The experts in the field of vitamin D have chosen the normal range of 25 (OH) vitamin D as 30-100 ng/ml (75-250 nmol/L) to provide a large safety margin.
In an excellent study (3) from the University of Toronto, Canada, researchers report 2 cases of high doses of vitamin D. The first gentleman had been taking 4,000 I.U./day for 3 years followed by 3 years of 8,000 I.U./day. Serum 25 (OH) vitamin D levels averaged 52 ng/ml , while taking 4,000 I.U./day of vitamin D3. While taking 8,000 I.U./day of vitamin D3, mean serum 25 (OH) vitamin D levels were 104 ng/ml . There was no evidence of vitamin D toxicity. He maintained a normal level of calcium in the blood and urine over the 6 years of the vitamin D3 intake.
The second gentleman was a 39-year-old man diagnosed with multiple sclerosis. He initiated his own dose-escalation schedule. He increased vitamin D3 dose from 8,000 to 88,000 I.U./day over a period of 4 years. At this extremely high dose, his blood 25 (OH) vitamin D level was 450 ng/ml , and his blood calcium was 2.63 mmol/L (reference range (2.2-2.6 mmol/L). As you can see, even at this super-high dose of vitamin D, his serum calcium was only slightly above the upper limit of normal, without any symptoms of toxicity. At this point, he stopped vitamin D3 supplementation. Two months later, his blood calcium values were within reference range; serum 25 (OH) vitamin D concentrations fell by about one-half, to 262 ng/ml . These results help to clarify the human response to higher intakes of vitamin D3.
I have seen several individuals who have been self-administering a daily dose of vitamin D3 as 15,000 to 30,000 I.U. for several years. Their 25 (OH) vitamin D level often gets above 100 ng/ml, but less than 130 ng/ml. None of them have experienced any vitamin D toxicity. Their calcium in the blood remains in the normal range
How Frequent Is Vitamin D Toxicity?
Extremely rare.
In medical literature, cases of vitamin D toxicity are rare.
A case of vitamin D toxicity was reported (4) from All India Institute of Medical Sciences, India. The patient was a 70-year-old woman with a long-standing history of hypertension and diabetes. She presented with decreased appetite, constipation and episodes of transient loss of consciousness. Her total blood calcium was 12.4 mg/dL (normal range 8.5-10.5 mg/dL) and vitamin D level was 2016 ng/mL . A retrospective analysis of her treatment history revealed that the patient had received 4 intramuscular injections of Architol (vitamin D3), each of 600, 000 I.U. , prior to coming to the hospital. With treatment, she recovered.
In another excellent study (5) from SheriKashmir Institute of Medical Sciences, India, researchers described 10 cases of vitamin D toxicity over a decade since 2000. The dose of vitamin D ranged from 3.6 million I.U. to 210 million I.U. over periods ranging from 1 - 4 months. These patients presented with vomiting, excessive urination, excessive thirst, confusion and kidney failure. Nine individuals recovered, while one died due to overwhelming infection.
Another study (6) came from Columbia University College of Physicians and Surgeons, USA. Researchers described 9 patients who presented with elevated 25 (OH) vitamin D levels. All of these individuals reported recently taking an over-the-counter vitamin supplement called Soladek readily available in the Dominican Republic and in Upper Manhattan. Each 5-ml vial of Soladek contains vitamin D3 (864,000 I.U. ) and vitamin A (predominantly retinyl palmitate 123,500 I.U.). The researchers noticed another interesting fact: Most of these patients had a disorder that can be associated with high calcium level: one had squamous cell cancer of the neck, one had Pneumocystis infection, three had mycobacterial infections, one had lymphoma, one had granulomatous disease and two had hyperthyroidism.
It is pretty obvious that all of these patients with vitamin D toxicity were taking an extremely high dose of vitamin D.
Most of my patients take a daily vitamin D3 dose of 5000 I.U. to 15,000 I.U. (125 mcg to 375 mcg.) I check vitamin D level in all of my patients and have been doing so over the last thirteen years. In the last fifteen years, I haven’t seen a single case of vitamin D toxicity in my patients while they are on vitamin D3 or D2 supplementation! Most of these patients have a level of 25 (OH) vitamin D less than 100 ng/ml. Rarely, I see someone with a level above 100 ng/ml (250 nmol/L), but less than 130 ng/ml (325 nmol/L.) Even in these patients, blood calcium is almost always normal.
Rarely, I see a patient with a slight increase in calcium level above the normal limit. Simply reducing calcium intake brings the calcium back into the normal range in these patients. I don’t consider this slight increase in the calcium level as a case of vitamin D toxicity.
Risk Of Toxicity; Over The Counter Vitamin D3 Versus Prescription Vitamin D, Calcitriol (Rocaltrol).
Let me clarify another issue. When medical writers of newspaper and magazine articles talk of vitamin D toxicity, they make a blanket statement about vitamin D supplements which is a mistake. There are several different preparations of vitamin D supplements. These include Vitamin D3 (cholecalciferol), Vitamin D2 (ergocalciferol), Calcidiol and Calcitriol. Calcitriol is also known as the brand name Rocaltrol.
Calcitriol (Rocaltrol) is a synthetic form of vitamin D and is a drug rather than a supplement. Therefore, it requires a prescription from a physician. It is typically given to patients who have kidney failure and are on dialysis. Calcitriol (Rocaltrol) is also sometimes prescribed to patients whose parathyroid glands have been removed, often inadvertently by a surgeon during thyroid surgery. Calcitriol (Rocaltrol) is much more potent than natural vitamin D3 or D2 and can sometimes result in vitamin D toxicity. Physicians who prescribe calcitriol (Rocaltrol) are typically aware (and definitely should be aware) of this possibility and monitor their patients for vitamin D toxicity.
Can You Develop Vitamin D Toxicity From Too Much Sun?
The answer is No. You can’t develop vitamin D toxicity from too much sun exposure. The reason? Nature is smart. The skin forms as much vitamin D as the body needs. Beyond that, it degrades any excess vitamin D into inactive metabolites. Pretty smart!
How Do You Detect Vitamin D Toxicity?
Vitamin D helps in the absorption of calcium from the intestines. Toxic levels of Vitamin D can cause an increase in blood level of calcium. Thus, vitamin D toxicity manifests itself as a high level of calcium in the blood.
The simplest and the most scientific way to find vitamin D toxicity is to check your calcium and vitamin D level in the blood. Everyone should have his/her vitamin D level and calcium checked every three months.
Symptoms Of Vitamin D Toxicity
Symptoms of vitamin D toxicity are due to increase in the blood level of calcium.
Mild increase in blood calcium level : Usually doesn’t cause any symptoms.
Moderate increase in blood calcium : Usually causes non-specific symptoms of nausea, vomiting, constipation, poor appetite, weight loss and weakness. Remember these symptoms can be caused by a variety of other medical conditions as well.
Severe increase in blood calcium level : Causes neurologic symptoms such as somnolence, confusion, even coma and heart rhythm abnormalities which can be fatal if not treated promptly.
Treatment OF Vitamin D Toxicity
Rarely, I see a patient whose blood calcium goes slightly above the upper limit of normal while on vitamin D supplementation. I lower their calcium intake and repeat a blood test for calcium in a month. In my experience, the reduction in calcium intake brings down calcium into the normal range.
Very rarely, blood calcium remains slightly elevated. I then check parathyroid hormone level. If it is in the normal range, then I further discuss diet with the patient and try to lower calcium intake. Even in these very rare patients, blood calcium normalizes by lowering their calcium intake. I also keep in mind other causes for elevated blood calcium level such as primary hyperparathyroidism and cancer. I order diagnostic testing in this regard on a case by case basis. If blood calcium is elevated and parathyroid hormone (PTH, intact) is also elevated and both of these values do not normalize with vitamin D supplementation, then that patient is most likely suffering from primary hyperparathyroidism. If parathyroid hormone (PTH, intact) level is normal and the patient continues to have an elevated calcium level, I investigate the possibility of other causes of high calcium such as Cancer, granulomatous diseases and Benign Familial Hypocalciuric Hypercalcemia.
Rarely, high blood calcium may occur due to vitamin D toxicity which can happen if very high doses of vitamin D are used (such as more than 50,000 I.U. per day) for a long period.
Remember, there are many causes of an increase in blood calcium level other than vitamin D toxicity. Two such common causes of high blood calcium are: Primary hyperparathyroidism and cancer. If you have high blood calcium, your physician should thoroughly look into various causes of high blood calcium.
It’s important to notify your physician about all the dietary supplements, including vitamin D, which you take. Most physicians don’t specifically ask about dietary supplements and often patients don’t think to provide this information either. For best medical care, your physician should know all the medicines as well as all the dietary supplements that you take. If your physician determines that a mild increase in your blood calcium level is due to excessive doses of “over the counter” vitamin D supplementation, as evidenced by a high blood level of 25 (OH) vitamin D, you should decrease the dose of your calcium intake in consultation with your physician. In most cases, simply reducing the calcium intake will bring calcium back into the normal range. If your physician advises you to reduce the dose of vitamin D, you should do so. Recheck your calcium level in a month or so to make sure that your blood calcium is back to normal. Recheck your vitamin D and calcium in about 3 months to make sure that these levels are good and you haven’t swung in the other direction.
If your blood calcium is high due to “prescription vitamin D”, such as calcitriol , the treatment will depend upon the degree of high blood calcium and your symptoms. Your physician will manage it accordingly. If your calcium level is moderate to severely high, your physician will likely admit you to the hospital for proper treatment of vitamin D toxicity.
References:
1. Jones G. The pharmacokinetics of vitamin D. Am J Clin Nutr . 2008 Aug;88(2):582S-586S.
2. Shepard RM, DeLuca HF. Plasma concentrations of vitamin D3 and its metabolites in the rat as influenced by vitamin D3 or 245-hydoxyvitamin D3 intakes. Arch Biochem Biophys 1980;202:43-53.
3. Kimball S, Vieth R. Self-prescribed high-dose vitamin D3: effects on biochemical parameters in two men. Ann Clin Biochem. 2008 Jan;45(Pt 1):106-10.
4. Garg G, Khadgwat R, Khandelwal D, Gupta N. Vitamin D toxicity presenting as hypercalcemia and complete heart block: An interesting case report. Indian J Endocrinol Metab. 2012 Dec;16(Suppl 2):S423-5
5. Koul PA, Ahmad SH, Ahmad F, Jan RA, Shah SU, Khan UH. Vitamin d toxicity in adults: a case series from an area with endemic hypovitaminosis d. Oman Med J . 2011 May;26(3):201-4
6. Lowe H, Cusano NE, Binkley N, Blaner WS, Bilezikian JP. Vitamin D toxicity due to a commonly available “over the counter” remedy from the Dominican Republic. J Clin Endocrinol Metab . 2011 Feb;96(2):291-5