Holick and his colleagues sent out detailed questionnaires to the first eight patients that were identified. “And bingo,” recalls Holick, “all of them drank a lot of milk.” The last piece of the puzzle now fell neatly and (for these kinds of investigations) rapidly into place. Not only did these patients drink a lot of milk, but they all got their milk from the same dairy, Crescent Ridge, in Sharon, Massachusetts, a small familyrun business serving roughly eleven thousand customers in twentyeight towns in the Boston metropolitan area.
At this point, the Massachusetts Department of Public Health launched a full-scale investigation. But first it ordered Crescent Ridge to stop adding vitamin D to its products. On July 3, 1991, the department sent a notice to area physicians, local boards of health, and customers of Crescent Ridge. It suggested that anyone who had drunk any milk from the dairy since January 1991 have blood tests for calcium and vitamin D levels. The letter read:
It has come to our attention that an excess amount of vitamin D was added to some milk [products] at the Crescent Ridge Dairy. The dairy has been cooperative and has participated in our efforts to solve this problem. Vitamin D is an optional supplement for milk and the dairy has stopped adding it to its milk since the problem was discovered. . . .
Because the symptoms are vague, we are advising that anyone who has been drinking milk from the Crescent Ridge Dairy since January 1, 1991, should contact their health provider to have blood tests done for calcium. Please bring this notice to your heath care provider. If your calcium is elevated, further medical evaluation will be needed.
The local media quickly picked up the story, and area labs were inundated with requests for blood work. At the Newton Wellesley Hospital, which serves many of the communities where the dairy delivered its products, the lab was inundated. The lab manager said, “Whole families were coming in with the letters [from the public health department]. Many people were quite anxious. We normally will draw blood from about 100 outpatients per day, and over that July Fourth weekend, we were doing 250 and more. Even people who weren’t customers of that dairy were asking to have their blood drawn.” Of the 1,000 patients tested over a two-week period, only 15 had elevated blood calcium levels; at another nearby hospital, 4 of 630 tested were positive.
Federal regulations state that one quart of milk should contain four hundred international units (ten micrograms) of vitamin D. Toxicity from too much vitamin D is quite rare, but it does happen. The members of one Scottish family fell ill just before Christmas of 1981. The two parents and four children all developed nausea, vomiting, and excessive thirst. The three eldest children, who were boys, were most severely affected; the eleven-year-old needed to be hospitalized first, initially with a diagnosis of “food poisoning.” His two brothers needed to be hospitalized over the next forty-eight hours. Doctors found it odd that although they were all dehydrated, their blood pressures were elevated, not low.
Then the doctors found that each one had a severely elevated serum calcium level. So did their seventeen-month-old sister and both parents. Their PTH levels were low, and their vitamin D was high. Something at the house was poisoning them with vitamin D. The levels of calcium fell rapidly, but it took months for the vitamin D levels to fall, partly because it is a fat-soluble vitamin (which helps explain why sun exposure during the summer helps keep the vitamin levels elevated for several months into the fall and winter). The father’s peak vitamin D level was 1,287 nanograms per milliliter, almost 25 times higher than the top normal of 50. Despite a thorough search of the house, the public health authorities never found the causative food.
In another case, a healthy two-year-old Hispanic child was seen in an emergency room for constipation and abdominal pain. He was released after a normal physical examination, although the blood pressure was slightly elevated. His mother brought him back the next day for continued symptoms. Again, except for an elevated blood pressure, his exam was normal, but this time the doctor sent blood work. The boy’s calcium was elevated, at 14.4 milligrams per deciliter.
On taking the boy’s history, the doctors found that his mother was giving him a vitamin D supplement called Raquiferol, normally sold in Latin America but available in bodegas in the United States as well. The recommended dosage was two drops (from an ampoule) per day, but the mother had given the boy a full ampoule each day for four days in a row. Each ampoule contained 600,000 international units (IU). The adequate intake for toddlers is about 200 IU per day; the boy had received 3,000 times the recommended amount. He was severely vitamin D toxic and severely hypercalcemic. After two weeks in the hospital he improved, and fortunately he suffered no lasting effects.
In another bizarre case, a one-year-old dog, a nineteen-pound pug, became toxic from his owner’s medication. The owner used a vitamin D analog called calcipotriene cream to treat his psoriasis. The dog was used to licking the owner’s skin, and apparently liked the taste of the medicated cream. One day when the medication was inadvertently left unattended, the dog consumed the remainder of a tube of the medicine. Within forty-eight hours, the dog started to vomit blood and seemed unusually fatigued. Despite treatment, the dog died of severe hypercalcemia.
When Holick and the other investigators tested the milk, their results were nothing less than astonishing. Crescent Ridge’s homogenized whole milk sold in April 1991 had a vitamin D level of 232,565 IU per quart—nearly 600 times the acceptable amount. Milk from two months later, however, in June, had nearly undetectable amounts. The non-fat and low-fat milk also had levels of vitamin D that were between 75 to 150 times higher than recommended.
Authorities are still not sure precisely how this happened. The concentrate of vitamin D that the dairy employees added to the milk was vitamin D2, labeled as containing 400,000 IU per milliliter. But when Holick had the concentrate tested, it gave results as if it were vitamin D3. Initially, this finding nearly threw the investigators off track. Either the lab was not doing the test correctly, or the dairy was wrong about its D2. But another possibility was that it was not the dairy’s fault at all.
Holick was convinced that the source of the problem had to be the dairy. Finally, after repeated testing, he proved that the additive was actually D3, a finding he confirmed by having it submitted to mass spectrophotometry at the National Institutes of Health. The manufacturer, Freeman Industries in New York, had been mislabeling the product. In terms of toxicity, the mislabeling was not a major issue, although vitamin D3 is about three times stronger than D2, so the effects of this error were compounded. More important was that it delayed the investigation by a few months.
On top of everything else, the highly concentrated vitamin solution was being added to the milk by hand at Crescent Ridge (as it is at half the dairies in the country); the investigators speculated that the extreme dosage could have simply been a result of human error.
At last the mysterious symptoms began to make sense for Virginia Palazzo and Lou Goldberg, both of whom were Crescent Ridge customers.
“I was worried that my kids would suffer growth problems or kidney damage,” Virginia says. Luckily, that did not occur. “It wasn’t easy keeping an eight-year-old and an eighteen-month-old out of the sun or covered up with sunscreen all summer, but you do your best,” says Palazzo.
Lou Goldberg was relieved as well. “I can’t drink a lot of sweet sodas and juices because of my diabetes,” she explains. “And because I am allergic to aspartame, diet sodas are out, and I don’t like coffee or tea. So I’ve always enjoyed milk. I drink loads of it. Some people are alcoholics; I drink a lot of milk, but I had to decrease my milk intake, so I did.”
It’s not known exactly how many people experienced symptoms of hypercalcemia, but the number was likely low given how few patients who were tested actually had elevated calcium levels.
The incident at Crescent Ridge sparked calls for a reevaluation of milk processing and inspection nationwide.
Soon afterward, Holick checked out other brands of milk, buying forty-two samples fro
m various dairies and supermarkets in five eastern states. The first results of his investigation, published in the New England Journal of Medicine, were unsettling. Out of all forty-two containers labeled “vitamin-D fortified,” 80 percent fell outside the acceptable range. Sixty-two percent of those quarts contained too little vitamin D (some had none at all), which could be harmful for youngsters or older women, many of whom depend on milk for their daily requirements. The remainder had too much vitamin D (though none had levels as high as Crescent Ridge’s).
He also tested infant formula from five major national suppliers. All contained more than 150 percent of the amount of vitamin D stated on the label. While no life-threatening overdoses were found, the study demonstrates how easily an error could go undetected.
It’s not mandatory that vitamin D be added to milk, but most dairies do fortify their product. Those that do are required to state it on the label. The mandated amount is 400 IUs per quart, but regulations permit a 140 percent margin of error.
Monitoring of vitamin D levels and other safety issues, such as bacterial contamination, is under the control of the FDA if the milk is sold across state lines. Small dairies like Crescent Ridge, which sell their milk in only one state, are not under federal jurisdiction, but they are supposed to test their milk twice a year to be sure that the amount of vitamin D falls within the range stipulated by the FDA.
Budget cuts have affected the FDA’s ability to properly inspect milk. In response to the outbreak, an article in the Boston Globe on July 21, 1991, reported:
The FDA has only 23 people assigned to milk safety nationwide, down from 33 a decade ago. The job of overseeing the system in New England has changed hands five times in the last eight years. The last person to hold it left last week. The federal agency is responsible for close to 1000 dairies and 150,000 farms.
Budget-strapped state governments, which share responsibility with the FDA, are cutting their milk inspection staffs. In the past two years, the New England states have sliced the number of inspectors by more than a third to 35. According to the FDA, four of the six states do not perform the test that would have caught the problem at [Crescent Ridge] even though federal rules require it be done.
In the same article, the director of the Massachusetts Department of Public Health’s food and drug division said of that test, “We haven’t done it in years. We don’t have the [personnel].”
Despite this outbreak of vitamin D toxicity, the vitamin’s use in milk is important. In Britain, in 1956, the British Pediatric Society found that 204 cases of hypercalcemia from vitamin D intoxication had occurred over a two-year period. This resulted in the cessation of the vitamin D milk fortification program in Great Britain. But when the incidence of rickets shot up as a result, the experiment was quickly abandoned. Nevertheless, these cases show that, as with all beneficiary interventions, they must be implemented wisely and cautiously.
All that said, the Crescent Ridge case clearly illustrates the potential toxic effects of excessive vitamin D. Holick and other experts urge that dairies use advanced measurement and quality-control techniques and that regulatory agencies enforce guidelines by routinely analyzing the vitamin D content of fortified foods. Even simple quality assurance measures would have shown a serious problem. Had the dairy been using the supplement correctly, it should have been using less than three bottles of the vitamin concentrate each year. But according to Massachusetts officials, Crescent Ridge used fifty-five bottles in 1989 and eighty-five bottles in 1990.
In the Crescent Ridge outbreak, the first case that was identified occurred roughly a year before the last one, and the dairy had been adding too much vitamin D in its milk for two years before the outbreak surfaced. Putting this together was in part fortuitous but in part related to the cooperative spirit of Boston’s doctors. Holick and his co-authors wrote in their medical report of the affair: “This study illustrates the importance of discussing cases that do not appear to have an explanation in a hospital or inter-hospital conference. It is from such a forum that a unifying thread may emerge. The search for a common vehicle in these cases led to a review of each patient’s dietary history (with use of a questionnaire) that in no instance revealed the ingestion of an unusual type or amount of food. All patients, however, obtained their milk from the same dairy.” Without that conference, it’s quite possible that many more people would have become affected and some might have had worse outcomes.
In fact, one seventy-two-year-old woman from Norwood, Massachusetts, had a prolonged hospitalization and died, although the precise contribution of the hypercalcemia is not known. As for Lou Goldberg, she drastically cut down on milk intake, and by August 1991, she was feeling perfectly normal. Similarly, the Palazzo children were also fine in the end. Both the children and Ms. Goldberg had follow-up calcium levels that were normal, and fortunately none of them seemed to have any long-lasting effects.
Sources
Some of the pieces in this book were previously published in shorter forms and, in some cases, under different titles. The chapters that first appeared in Boston Magazine are “A Study in Scarlet” ( June 1989, under the title “Something Fishy”), “An Airtight Case” (September 1989), “Feeling His Oats” ( January 1990), “The Case of the Wide-Eyed Boy” (May 1990), and “The Case of the Overly Hot Honeymoon” (October 1990, under the title “The Woman Who Ate Too Much”). Those that appeared in Ladies’ Home Journal are “The Deadly Dinner Party” (May 1990, under the title “The Case of the Deadly Dinner Party”), “The Baby and the Bathwater” (February 1991, under the title “The Case of the Careful Babysitter”), “Too Much of a Good Thing” (September 1992), “The Case of the Unhealthy Health Food” (February 1993), “The Forbidden Fruit” (October 1994, under the title “The Case of the Fallen Fruit”), and “Rubbed the Wrong Way” (November 1994, under the title “The Case of the Peculiar Pimples”).
Chapter 1. The Deadly Dinner Party
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