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Latest case-studies on vitamin D toxicity

Posted on: September 29, 2011   by  John Cannell, MD

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In September, 2011, two papers with three case reports of vitamin D toxicity were published. Two cases were manufacturing errors and one was a pharmacist’s mistake. Vitamin D levels associated with clear toxicity ranged from 194 to 1220 ng/ml. To my knowledge, toxicity occurring at 194 ng/ml is the lowest vitamin D level causing clear toxicity known in the medical literature.

In the first case, a pharmacist’s dispensing error occurred when the doctor wrote a prescription for 1,000 IU/day of D3. Since it was not a prescription item, the pharmacist thought the doctor meant prescription Drisdol, which is 50,000 IU. So the patient, a 70-year old woman with mild dementia, began taking 50,000 IU/day of D2. She was also taking, for reasons unknown, 3100 mg of calcium per day.

Jacobsen RB, Hronek BW, Schmidt GA, Schilling ML Hypervitaminosis D Associated with a Vitamin D Dispensing Error (October). Ann Pharmacother. 2011 Sep 13.

Three months later she developed confusion, slurred speech, unstable gait, and increased fatigue. Probably due to her dementia, she did not complain of the most common symptoms of toxicity: lack of appetite, excessive thirst, nausea, abdominal pain and increased urination. Her vitamin D level was 194 ng/ml, her calcium (CA) was 14.6 (8.5-10.5 is normal); her kidney function was impaired with a creatinine of 5.3 (CR); her activated vitamin D level was normal, her urine CA/CR ratio was elevated, but she had no anemia. All vitamin D and calcium was withheld and her doctors treated her with IV fluids. Four days later her symptoms disappeared and her calcium returned to normal and her creatinine improved to 3.0. Five months later her vitamin D level was 40, her calcium was 9.2, and her creatinine was back at baseline, 1.8.

To my knowledge, this is the first modern case report of toxicity at 50,000 IU/day (and this was D2), although this case also included 3100 mg/day of calcium. Unfortunately, I have heard that a few physicians use 50,000 IU/day routinely. It is too much, way too much. However, this lady completely recovered with no damage to her kidneys.

Secondly, why would anyone take 3100 mg/day of calcium? In this case she was demented. However, many people believe that the government recommendation of 1200 mg/day of calcium for females over the age of 50 means they should literally take 1200 mg/day as a supplement. It does not mean that at all. It means total dietary and supplement intake should be 1200 mg/day and everyone gets some calcium in their diet. Most people need no more than 500 mg/day of calcium as a supplement and many people who eat dairy three times a day need none.

The other two cases were equally interesting, but involved manufacturing errors. It is one of the reasons I recommend you get your vitamin D from one of our sponsors, Stop Aging Now or Bio-Tech-Pharmacal. Both companies are experienced and careful in their vitamin D manufacturing process.

In case two, an otherwise healthy man developed fatigue, excessive thirst, frequent urination and confusion. Three weeks later he was admitted to hospital in a coma with a vitamin D level of 1220 ng/ml (24 times that of a healthy level), calcium of 15, activated vitamin D of 106, massive calcium loss in the urine, mild anemia, and elevated urine CA/CR ratio. He had been taking “Formula F,” labeled to contain 1600 IU of vitamin D but it really contained 186,400 IU per capsule. In addition, “Formula F’s” label recommended 10 capsules per day, not one, so the patient had been taking 1,864,000 IU daily for two months! After treatment, calcium returned to normal in three weeks; the vitamin D level and the creatinine returned to normal in a year. That is, he completely recovered.

Araki T, Holick MF, Alfonso BD, Charlap E, Romero CM, Rizk D, Newman LG. Vitamin D Intoxication with Severe Hypercalcemia due to Manufacturing and Labeling Errors of Two Dietary Supplements Made in the United States. J Clin Endocrinol Metab. 2011 Sep 14.

Case three (in the above paper) was a 40-year old man who presented with excessive thirst, frequent urination, muscle aches, nausea, vomiting, elevated calcium (13.2), elevated creatinine (1.78), vitamin D level of 645 ng/ml, elevated activated vitamin D of 99, mild anemia, and an elevated urine Ca/Cr ratio. He reported taking “Gary Null’s Ultimate Power Meal” for a month, which mistakenly contained 970,000 IU of vitamin D per serving. Calcium returned to normal in several days, kidney function returned to normal in 4 weeks, vitamin D level normalized in 10 months but activated vitamin D took a year to normalize. No permanent injuries occurred, much to the chagrin of the trial lawyers.

The takeaway from these three papers is that if you take more than 10,000 IU/day, you must check your 25(OH)D regularly. I am concerned that people with levels greater than 150 ng/ml may be urinating out more calcium than they should; that is urinating out their bones. A 1988 paper suggested exactly that and I have clinic experience that shows in at least one person, a 24 hour urine calcium was elevated before the urine Ca/Cr ratio was abnormal. To be safe, keep your 25(OH)D vitamin D levels below 100 ng/ml.

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