Vitamins Vs. Vaccines Why FDA Regulation Is a Good Thing Paul A. Offit, MD

1. Vitamins Vs. Vaccines • Why FDA Regulation Is a Good Thing • Paul A. Offit, MD • The Children’s Hospital of Philadelphia • The University of Pennsylvania School of Medicine

2. Vitamins • Necessary to convert food into energy. • Water soluble: B1, B2, B3, B5, B6, B7, B9, B12, C; fat soluble: A, D, E, K.. • With the exception of B7 (biotin) and D, all vitamins must be obtained from foods. • Deficiencies lead to diseases like beriberi (B1), pellagra (B3), scurvy (C), and rickets (D), which can be avoided by ingesting the RDA (typically found in foods).

3. Vitamins as Antioxidants • Oxidation generates free radicals, which damage cell membranes, DNA, and the lining of arteries. • Antioxidants neutralize free radicals. • People who eat diets rich in fruits and vegetables that contain antioxidants like vitamins A, C, E, and beta-carotene have lower rates of cancer and heart disease.

4. If Vitamins are Good, Are More Better?

7. Vitamins: Too Much of a Good Thing? • In 1994, researchers from the NCI and Finland’s National Health Institute studied 29,000 men: all long-term smokers more than 50 years old. • Given vitamin E, beta-carotene, both or neither. • Vitamin recipients were at increased of lung cancer. • Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study Group, New England Journal of Medicine 330 (1994): 1029-1035.

8. Vitamins: Too Much of a Good Thing? • In 1996, scientists from the Hutchinson Research Center in Seattle studied 18,000 people who had been exposed to asbestos. • Given vitamin A, beta-carotene, both or neither. • Vitamin recipients died of cancer and heart disease at rates 28% and 17% higher, respectively. • G. E. Goodman, M. D. Thornquist, J. Balmes, et al., Journal of the National Cancer Institute 96 (2004): 1743-1750.

9. Vitamins: Too Much of a Good Thing? • In 2004, researchers in Copenhagen reviewed 14 randomized trials involving more than 170,000 people who had received vitamins A, C, E, and beta-carotene to prevent intestinal cancers. • Death rates were 6% higher in those taking vitamins. • G. Bjelakovic, D. Nikolova, R. G. Simonetti, et al., Lancet 364 (2005): 37-46

10. Vitamins: Too Much of a Good Thing? • In 2005, researchers at Johns Hopkins evaluated 19 studies of more than 136,000 people • Found an increased risk of death associated with vitamin E. “The evidence for supplementing with any vitamin is just not there. This idea that people have that [vitamins] will not hurt them may not be that simple.” • E. R. Miller III, R. Pastor-Barriuso, D. Dalal, et al., Annals of Internal Medicine 142 (2005): 37-46

11. Vitamins: Too Much of a Good Thing? • In 2008, a Cochrane collaborative reviewed existing studies of more than 230,000 people who did or didn’t take supplemental vitamins. • Found an increased risk of cancer and heart disease in those taking vitamins. • G. Bjelakovic, D. Nikolova, L. L. Gluud, et al., Cochrane Database of Systematic Reviews (2008): 2.

12. Vitamins: Too Much of a Good Thing? • In 2011, researchers at the Cleveland Clinic studied 36,000 men who took vitamin E, selenium, both or neither. • Those receiving vitamin E had a 17% increased risk of prostate cancer. • E. A. Klein, I. M. Thompson, Jr., C. M. Tangen, et al., Journal of the American Medical Association 306 (2011): 1549-1556

13. Vitamins: Too Much of a Good Thing? • In response, Steve Nissen, chairman of cardiology at the Cleveland Clinic: “The concept of multivitamins was sold to Americans by an eager nutraceutical industry to generate profits. There was never any scientific data supporting their usage.” • Headline in the Wall Street Journal: “Is This the End of Popping Vitamins?” • S. S Wang, Wall Street Journal, October 25, 2011.

14. Impact of Studies • “The thing to do with [these reports] is just ride them out,” said Joseph Fortunato, chief executive of GNC Corporation. “We see no impact on our business.” • In 2010, the vitamin industry grossed $28 billion, up 4.4 percent from the previous year. • S. S Wang, Wall Street Journal, October 25, 2011.

15. The Antioxidant Paradox • Oxidation isn’t always a bad thing. • Need free radicals to kill invading pathogens and new cancer cells. Excess antioxidants can shift the balance away from needed oxidation. • Not a single national or international organization responsible for the public’s health recommends supplemental antioxidants for otherwise healthy people • B. Halliwell, The Antioxidant Paradox, Lancet 355 (2000): 1179-80.

16. Given the consistency of these studies, why doesn’t everyone know about the dangers of megavitamins?

17. History of Drug Regulation in America

18. “The story of drug regulation is built on tombstones.” --Michael Harris

19. “The Good Old Days” • In the late 1800s, medical hucksters could claim anything. • Didn’t have to show that products were safe or effective before sale. • Didn’t have to list ingredients on the label. • Didn’t have to manufacture products in accordance with any standard.

25. Patent Medicines • By the turn of the century, patent medicines were a $75-million-a-year business. • The end ofAmerica’s Wild West Medicine Show began on June 30, 1906, with passage of the Pure Food and Drug Act. • First attempt in the United States to regulate drugs. Precipitated by two events.

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28. “The Great American Fraud” • Adams exposed 264 companies and individuals, listed scores of people who had died from dangerous drugs, and showed that many patent medicines had caused diseases rather than treated them. • Unknown to consumers, many products contained alcohol and narcotics. • Read by more than 500,000 Americans.

34. Upton Sinclair, “The Jungle” • “There would be meat stored in great piles in rooms, and the water from leaky roofs would drip over it and thousands of rats would race about on it. It was too dark in these storage places to see well, but a man could run his hand over these piles of meat and sweep off handfuls of the dried dung of rats…Packers would put poisoned bread out for them; they would die and then rats, bread and meat would go into the hoppers together.”

35. Pure Food and Drug Act of 1906 • Signed into law by President Theodore Roosevelt. • Not particularly effective, but it was a start. • Drugs still didn’t have to be proven safe or effective or manufactured under sanitary conditions before sale. • Companies could sell drugs containing alcohol, cocaine, morphine, and chloroform, but they had to print these ingredients on the label.

38. Elixir Sulfanilamide Disaster • Sulfa drugs developed in the 1930s, but not palatable for children. • Massengill Company of Bristol, Tennessee, suspended drug in diethylene glycol. • Ten months before marketing product, company found that it caused kidney failure in rats. • 240 gallons distributed; 100 people died from kidney failure, 34 were children.

39. Elixir Sulfanilamide Disaster • Massengill’s president: “My chemists and I deeply regret the fatal results, but there was no error in the manufacture of the product. I do not feel there was any responsibility on our part.” • No law had been broken. Company had complied with weak federal regulations. • Chief chemist at Massengill, Thomas Watkins, killed himself.

40. Food, Drug, and Cosmetic Act of 1938 • Signed into law by Franklin Delano Roosevelt. • Drugs had to be proven safe before licensure by FDA. • FDA also had to inspect and license manufacturing plants every two years. • Manufacturers still didn’t have to prove that their products were effective. It took another tragedy to get there.

42. The Thalidomide Disaster • On October 1, 1957, Chemie Grunenthal, a West German company, distributed thalidomide. • Advertised as a sedative, claimed to be safe, even for pregnant women. • Damaged more than 24,000 fetuses, causing phocomelia; half died before birth. • Although never licensed in US, led to next major piece of federal legislation.

43. Kefauver-Harris Amendment of 1961 • Modification of the 1938 Food, Drug, and Cosmetic Act. • Drugs had to be proven effective before licensure, even though thalidomide was a safety issue. • Previously licensed drugs could be withdrawn if found to be unsafe after licensure. • Prescription drugs had to include summary of side effects.

44. Kefauver-Harris Amendment of 1961 • Manufacturers had to obtain consent from patients before testing experimental drugs. • Product labels had to include exact quantities of all ingredients. • Manufacturers had to adhere to Code of Good Manufacturing Practices. • Looked like the end of America’s Wild West Medicine Show.

45. The First Giant Step Backwards

46. Vitamin Deregulation • Because of the influence of Linus Pauling, Americans were consuming vitamins in quantities far greater than the RDA. • In December 1972, the FDA announced plans to require vitamin makers to show proof of safety for vitamins in excess of 150% of the RDA. • Vitamin makers saw this as a threat to their $700-million-a-year industry.

47. Vitamin Deregulation • Vitamin manufacturers backed a bill proposed by Senator William Proxmire (D, Wisconsin) banning the FDA from regulating megavitamins. • Bill cosponsored by Bob Dole, Barry Goldwater, William Fulbright, Hubert Humphrey, George McGovern, and Sam Nunn. • In 1974, Proxmire’s bill was debated before Senator Edward Kennedy’s Subcommittee on Health.

48. Marsha Cohen, Consumer’s Union • “You would have to eat eight cantaloupes to take in barely 1,000 milligrams of vitamin C. But just these two little pills, easy to swallow, contain the same amount. If the proponents of the legislation before you succeed, one tablet would contain as much vitamin C as all of these cantaloupes—or even twice, thrice or twenty times that amount. And there would be no protective satiety level.”

49. Vitamin Deregulation • Proxmire’s bill passed by vote of 81-10. • On April 23, 1976, it became law. • The FDA was now banned from regulating megavitamins. Peter Barton Hutt, the FDA’s chief counsel: “It was the most humiliating defeat in the history of the FDA.” • No package inserts, no warning labels