Vitamins Vs. Vaccines

Why FDA Regulation Is a Good Thing

Paul A. Offit, MDThe Children’s Hospital of Philadelphia

The University of Pennsylvania School of Medicine

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).

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.

If Vitamins are Good, Are More Better?

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.

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.

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

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

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.

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

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.

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.

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.

Given the consistency of these studies, why doesn’t everyone

know about the dangers of megavitamins?

History of Drug Regulation in America

“The story of drug regulation is built on tombstones.”

--Michael Harris

“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.

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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“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.

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.”

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.

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.

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.

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.

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.

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.

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.

The First Giant Step Backwards

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.

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.

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.”

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

The Second Giant Step Backwards

Supplement Deregulation

• By 1990, FDA officials worried that sales people in health food stores were advising customers to treat high blood pressure, infections, and cancer with vitamins, supplements, minerals, and herbs.

• “We are back at the turn of the century when snake oil salesmen could hawk their potions with promises that couldn’t be kept,” said David Kessler. “We have not approved the safety of these products nor substantiated their claims.”

Supplement Deregulation

• On June 7, 1991, Henry Waxman, with the support of Kessler, introduced the Food, Drug, Cosmetic, and Device Enforcement Amendment.

• The amendment “authorized any district court to order the recall of a food, drug, device, or cosmetic which is in violation of the [law] if the violation involves fraud or presents a significant risk to human or animal health.”

Supplement Deregulation

• The industry countered with the Dietary Supplement Health and Education Act (DSHEA), recruiting Senator Orrin Hatch (R, Utah). Four of the industry’s top thirty supplement makers were located in Utah.

• Peter Barton Hutt: “Kessler wanted to drive a stake into the heart of the dietary supplement industry. Instead, he drove it into the heart of the FDA.”

Supplement Deregulation

• On May 11, 1994, the Dietary Supplement and Health Education Act (DSHEA) became law.

• A supplement was defined as “a product intended to supplement the diet that bears or contains one or more of the following ingredients: a vitamin, a mineral, an herb or other botanical, or an amino acid.”

• The New York Times called it, “The Snake Oil Protection Act.”

D. O. Clegg, D. J. Reda, C. I. Harris, et al., “Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis,” New England Journal of Medicine 354 (2006): 795-808.

C. D. Gardner, L. D. Lawson, E. Block, et al., “Effect of Raw Garlic Vs. Commercial Garlic Supplements on Plasma Lipid Concentrations in Adults with Moderate Hypercholesterolemia,” Archives of Internal Medicine 167 (2007): 346-353.

S. T. DeKosky, J. D. Williamson, A. L. Fitzpatrick, et al., “Gingko Biloba for Prevention of Dementia: A Randomized Controlled Trial,” Journal of the American Medical Association 300 (2008): 2253-2262.

S. Bent, C. Kane, K. Shinohara, et al., “Saw Palmetto for Benign Prostatic Hyperplasia,” New England Journal of Medicine 354 (2006): 557-566; K. J. Kreder, A. L. Avins, D. Nickel, et al., “Effect of Increasing Doses of Saw Palmetto Extract on Lower Urinary Tract Symptoms,” Journal of the American Medical Association 306 (2011): 1344-1351

With dietary supplements, lack of efficacy isn’t the only

issue

What You Don’t Know Can Hurt You

• Blue cohash: heart failure

• Nutmeg: hallucinations

• Comfrey, kava, chaparral, Crotalalaria, Senecio, Jin bu huan, Usnea lichen, and valerian: hepatitis

• Monkshood and plantain: arrythmias

What You Don’t Know Can Hurt You

• Wormwood: seizures

• Stevia leaves: decreased fertility

• Concentrated green tea extracts: liver damage

• Milkweed seed oil and bitter orange: heart damage

What You Don’t Know Can Hurt You

• Thujone: neurological damage

• Concentrated garlic: bleeding

• Pennyroyal and capsaicin: infant death

• Since the DSHEA went into effect, 51,000 new dietary supplements have come onto the market. 170 (0.3%) have documented safety tests.

Supplement Disasters

• In 1992, about 100 people developed kidney failure from a “slimming” mixture containing Aristolochia.

• Seventy patients required renal transplants or dialysis, many later developed bladder cancer.

Supplement Disasters

• In 2008, more than 200 people—including a 2-year old—were poisoned by massive doses of selenium contained in Total Body Formula and Total Body Mega.

• The label stated 200 mg per serving; products actually contained 40,800 mg.

Supplement Contaminants

• In 2004, researchers at Harvard Medical School tested ayurvedic (Indian) remedies in Boston.

• 20% contained potentially harmful levels of lead, mercury, and arsenic.

• In 2009, Kirkman Laboratories, which makes “remedies” for children with autism, recalled 15,000 bottles of zinc because they contained undeclared levels of antimony.

Supplement Contaminants

• In 2013, FDA recalled vitamin and mineral products made by Purity First because they were all contaminated with dimethazine and methasterone: anabolic steroids.

• Women developed loss of menstrual periods, hirsutism, and deepening of their voices.

• CEO of Purity First claimed it was a “government ploy to drive small vitamin makers out of business.”

Supplement Manufacture

• In 2007, FDA granted permission to supervise supplement manufacture.

• 450 inspected; half had significant problems.

• One substituted ingredients without changing the product label

• One didn’t have recipes for their products

• Some manufactured in buildings contaminated with rodent feces and urine

DSHEA: The Act No One Knows About

• 68% of Americans believe that the FDA requires supplement manufacturers to report side effects.

• 58% believe the FDA must approve supplements before sale.

• 55% believe manufacturers of vitamins, minerals, and supplements cannot make claims about safety and effectiveness without scientific proof.

Vaccines Are What They’re Claimed to Be

Vaccines are tightly regulated

• The conjugate pneumococcal vaccine was tested in 37,000 children before licensure

• The HPV vaccine was tested in 30,000 women for 7 years before licensure

• Rotavirus vaccines were tested in 130,000 children before licensure

Vaccine Safety DataLink

• Established in 1990.

• Linked, computerized medical records from 9 managed care organizations.

• Allows CDC to quickly determine whether a new vaccine has a particular side effect.

Serious Adverse Reactions to Vaccines

• Yellow fever vaccine causes systemic disease in the elderly—about 50 deaths.

• OPV: paralytic polio in 1 per 2.4 M doses

• Measles vaccine: thrombocytopenia in 1 per 25,000 doses

• Pandemrix: narcolepsy in 1 per 55,000 doses

• 1976 Swine flu: GBS in 1 per 100,000 doses

Vitamins and Supplements Vs. Vaccines

• Parents are often fearful of vaccines, the product of a highly regulated industry that requires proof of safety, efficacy, and standards of manufacture.

• Parents aren’t fearful of vitamins and supplements, even though they might be unsafe, contain harmful contaminants, or made under unsanitary conditions.