Should Vitamins Be Regulated As Drugs?

Each year, the vitamin and mineral supplement industry rakes in bil­lions of dollars in the United States.

The industry has done a very ef­fective job making Americans believe that these supplements are both safe and necessary. Even when they are not at risk of vitamin deficiency, many people still take supplementary vitamins because they think that these supplements are safe ways to ensure their health.

But what many people may not realize is that vitamin and mineral supplements are, like drugs, pharma­cologically active substances, meaning that they affect multiple parts of the body. All drugs have their downsides. Some of the potential side effects associated with vitamins are quite serious. These supplements can cause toxicity when taken in excessive doses, and they can also interact with prescription and over-the-counter (OTC) medications.

Safety concerns such as these prompted Canadian researchers to publish an article in the February 2010 Annals of Pharmacotherapy ex­amining whether vitamins should be regulated as drugs.

The authors of this article (and our staff) do not suggest that vitamins should be banned or classified as pre­scription drugs if they are not already classified that way (such as injectable vitamins). Instead, they propose regu­lating vitamin and mineral supple­ments as OTC drugs — after all, some vitamin producers are already promoting their products as drugs for the prevention and treatment of diseases. This would mean manufac­turers would have to provide evidence of both efficacy and safety.

Because most vitamins currently fall in the category of dietary supple­ments, and dietary supplements are wrongly exempt from the drug safety and efficacy requirements, the Food and Drug Administration (FDA) lacks the regulatory authority to require warnings on the labels of vitamin products. Unlike a dietary supplement, a product that is classi­fied as an OTC drug may be required to include safety information on its packaging.

We agree with the authors of the study that consumers should have the basic right to be warned of these potential side effects on the labels of the products they purchase: Vitamins should be regulated as OTC drugs.

What You Can Do

There are some conditions of vitamin deficiency that require medi­cal treatment with vitamins and are therefore already regulated by the FDA. For example, injectable vita­min K, vitamin D and vitamin B12 are FDA-approved and regulated as prescription drugs.

Not everyone is at risk of vitamin deficiency, and vitamin and mineral supplements are therefore not ap­propriate for everyone. Talk to your physician before starting any new supplement. Do not assume that vitamins, particularly in large doses, are harmless.

Consumers may report serious adverse events or product quality problems with the use of vitamins to the FDA’s MedWatch Adverse Event Reporting program either online, by regular mail, fax or phone.

Online: https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
Regular Mail: Use postage-paid FDA form 3500 and mail to Med­Watch, 5600 Fishers Lane, Rockville, MD 20852-9787
Fax: (800) 332-0178
Phone: (800) 332-1088

Side Effects of Vitamins
The following is a list of vitamins followed by the potential side effects of each. Vitamins are listed as fat- or water-sol­uble. Fat-soluble vitamins — vitamins A, D, E and K — are stored in the body and can accumulate, potentially causing toxicity. Water-soluble vitamins, however, are eliminated rapidly by the body and are less likely to cause toxicity.

Fat-Soluble Vitamins
Vitamin A – 3-dehydroretinol, retinoids, retinol, retinyl acetate, retinyl palmitate, carotenoids
Daily Maximum Recommended Intake: 900 micrograms, equivalent to 3,000 International Units (IUs)

Liver Toxicity
The damage from vitamin A rang­es from elevated blood levels of liver enzymes, which are early signals for potential liver toxicity, to widespread damage of the liver (hepatic fibrosis, cirrhosis and cell death), which can result in death.

Other Effects
Acute toxicity with doses of 50,000 IUs may result in nausea, vomiting, headache, increased pres­sure of spinal fluid, dizziness, blurred vision, muscular incoordination, and bulging between the skull bones in infants. Chronic use of this vitamin in high doses can cause lethargy, ir­ritability, loss of appetite, abdominal discomfort, nausea and vomiting, excessive sweating, itching, redness and increased coloration of the skin.
Slow growth has been seen in chil­dren who take high doses of vitamin A with premature closure of the growth plates in the bones, abnormal hardening of the bone, joint and muscle pain, and elevated levels of calcium in the blood and urine.

Birth Defects
Babies exposed to vitamin A in the womb may develop congenital abnormalities, including those of the skull and face, central nervous system, and defects of the heart and blood vessels. A study of 22,748 pregnant women in the U.S. found that among babies born to mothers taking over 10,000 IUs daily, 1 in 57 infants had a malformation linked to vitamin A.

Osteoporosis and Fracture Risk
Research has demonstrated that a high intake of retinol (a form of vi­tamin A) and vitamin A is associated with osteoporosis and an increased risk of fractures. These results were not from “gold” standard random­ized clinical trials; however, the re­sults of these studies were consistent and should be viewed as a serious warning.

Lung Cancer
A randomized clinical trial found an increase risk of lung cancer in male smokers taking beta-carotene, a plant source of vitamin A. Other studies have also found a link be­tween vitamin A and cancer.

Vitamin D – 1,25-dihydroxyc­holecalciferol, 25-hydroxychole­calciferol, alfacalcidol, calcife­diol, calcipotriene, calcitriol, cholecalciferol, dihydrotachys­terol, ergocalciferol, paricalcitol
Daily Maximum Recommended Intake: 15 micrograms, equivalent to 600 IUs

Symptoms of vitamin D toxic­ity include increased blood levels of calcium that can cause weakness, fatigue, sleepiness, headache, nau­sea, vomiting, diarrhea, dizziness, bone pain, irritability and low blood sodium in infants.

Kidney Problems
Vitamin D has also been associated with high blood levels of urea, uri­nary frequency, thirst and increased amounts of protein in the urine.

Kidney Stones
In a randomized clinical trial in women, the use of a combination of 400 IUs of vitamin D with 1,000 milligrams of elemental calcium increased the risk of kidney stones compared to placebo.

Other Adverse Effects
Vitamin D has also been associated with osteoporosis, decreased growth in children, weight loss, conjuncti­vitis, sensitivity to light, calcification of blood vessels, inflammation of the pancreas, generalized seizures, psychosis, increased cholesterol, liver enzymes and nitrogen in the urine.

Vitamin E – alpha-tocopherol, beta-tocopherol, delta-tocopherol, gamma-tocopherol
Daily Maximum Recommended Intake: 15 milligrams, equivalent to 22.5 IUs

Gastrointestinal (GI) Effects
In healthy adults, doses of 200 to 800 milligrams per day of vitamin E may cause GI upset.

Heart Effects
A trial in more than 11,000 patients with previous heart attacks suggested that vitamin E had no benefit. The 3.5-year follow-up of these patients showed that those who received vitamin E had a 20 percent increased risk of developing conges­tive heart failure, and there was a 50 percent increase of congestive heart failure in patients with heart dysfunction. One randomized trial looked at 9,500 participants who were at high risk for cardiovascular events. The study found that “treat­ment with vitamin E for an average of 4.5 years did not prevent cancer or major cardiovascular events but increased the risk for heart failure.”

Effect on Blood Clotting
Doses of 800 to 1200 milligrams per day of vitamin E might increase the risk of bleeding. This risk is particularly important in patients already taking anticoagulant or anti­platelet drugs to prevent blood clots.

Stroke
A primary prevention trial among almost 30,000 male smokers sug­gested a higher incidence of a certain type of stroke in smokers taking vitamin E.

Risk of Death
Some studies suggest that tak­ing high doses of vitamin E might increase the risk of death. A statistical summary of 19 clinical trials with more than 135,000 participants con­cluded that vitamin E in doses of 400 IUs per day or higher may increase mortality and should be avoided. A recent study showed that mortal­ity was increased in vitamin E users who had a history of stroke, coronary bypass graft surgery or heart attack.

Cancer
There is also concern about the effect of vitamin E supplements on the risk of cancer. An analysis of a large U.S. study involving more than 150,000 women found that blood levels of gamma-tocopherol (another form of vitamin E) was associated with increased risk of all breast can­cer and invasive breast cancer.

A study of 5,141 men random­ized to take either a placebo or supplementation with nutritional doses of vitamin C, vitamin E, beta-carotene, selenium and zinc daily for eight years found that patients with elevated prostate-specific antigen receiving the multivitamin/multi­mineral supplements had a higher incidence of prostate cancer. Accord­ing to one large-scale study, “men who take a multivitamin more than seven times per week and who also take a separate vitamin E supplement have a significantly increased risk of developing prostate cancer.”

Vitamin K – phytonadione [K1], menaquinone [K2], menadione [K3], menadiol acetate [K4], 4-amino-2-methyl-1-naphthol [K5]
Daily Maximum Recommended Intake: 120 micrograms

Painful swelling at site of vitamin K injection has been noted. There are reports of flushing, dizziness, increased risk of bleeding, excess bilirubin in the blood, liver dam­age in infants and children, and the breakdown of blood cells.

Water-Soluble Vitamins
Vitamin B1 – thiamin
Daily Maximum Recommended Intake: 1.2 milligrams

This vitamin can cause skin in­flammation and other hypersensitivi­ty reactions, including a risk of severe hypersensitivity reaction (anaphy­laxis) when injected. Also, injected vitamin B1 can cause tenderness and tissue changes at the injection site, as well as tingling, itching, pain, weak­ness, sweating, nausea, restlessness, respiratory distress, cyanosis, pulmo­nary edema, GI bleeding, vascular collapse and death.

Vitamin B2 – riboflavin, vitamin G, lactoflavin
Daily Maximum Recommended Intake: 1.3 milligrams

Large amounts of riboflavin (400 mg/day) taken orally might cause diar­rhea, frequent urination and a yellow-orange discoloration of the urine.

Vitamin B3 – niacin, niacinamide, nicotinic acid, vitamin PP
Daily Maximum Recommended Intake: 16 milligrams

Flushing Reaction
Niacin can cause a flushing reaction with itching, increased blood flow and headache with doses commonly used for treatment of high cholesterol (more than 30 milligrams per day).

Liver Toxicity
Niacin also can cause elevated liver enzyme levels and jaundice (yel­lowing of the skin and whites of the eyes), especially with doses of 3 grams a day or more, and cases of severe liver toxicity with inflammation of the liver and brain due to niacin have been reported. Niacin liver toxicity is more common with sustained-release prod­ucts that are used to lower cholesterol.

GI Effects
Large doses of niacin can cause symptoms such as nausea, vomiting, bloating, loss of appetite, diarrhea and peptic ulcers.

Effects on Blood Sugar
There is a disagreement in the medical literature as to whether or not niacin increases sugar and hemoglobin A1c levels, a measure of sugar control, in the blood.

Effects on Uric Acid Levels
Niacin in high doses has been shown to reduce urinary excretion of uric acid. It may also induce consistent increases in blood uric acid levels, and potentially cause gout.

Effects on Blood Pressure
Niacin dilates blood vessels and lowers blood pressure, which can cause rapid heart rate, heart rhythm disturbances and fainting, particularly in patients with high blood pressure taking medications.

Vitamin B5 – pantothenic acid, calcium D-pantothenate, D-pan­thenol, pantothenol
Daily Maximum Recommended Intake: 5 milligrams

Large amounts of pantothenic acid taken orally can cause diarrhea.

Vitamin B6 – pyridoxine
Daily Maximum Recommended Intake: 1.7 milligrams

Effects on Nerves
Vitamin B6 can cause reversible sensory nerve changes and gradual progressive muscle incoordination in doses greater than 1.0 grams daily, although toxicity can occur with lower doses.

Effects on Skin
Cases of a rapidly developing inflammatory disorder of the face, known as rosacea, is associated with daily ingestion of high-dose vitamins B6 and B12, and photosensitiv­ity caused by vitamin B6 has been described.

Other Effects
Vitamin B6 can cause nausea, vomiting, abdominal pain, headache, drowsiness, allergic reactions, and breast soreness or enlargement.

Vitamin B9 – folic acid, 5-meth­yltetrahydrofolate, folacin, folate, L-methyfolate
Daily Maximum Recommended Intake: 400 micrograms if from food, 200 micrograms if synthetic

GI Effects
This vitamin is well-tolerated when taken in doses less than 1.0 milligrams per day; however, doses over 5.0 mil­ligrams per day can cause abdominal cramps, diarrhea and rash.

Effects on Nervous System
Large doses of folic acid, more than 15 milligrams per day, can cause altered sleep patterns, irritability, con­fusion, worsening of seizure frequency, nausea and flatulence; they can also precipitate or exacerbate nerve changes in people deficient in vitamin B12.

Intellectual Decline
One study of 3,718 Chicago resi­dents found that people over 65 years of age who consumed an average of 0.74 milligrams per day of folic acid had twice as rapid cognitive decline than those consuming an average of 0.19 milligrams per day.

Effects on the Heart
Two multicenter randomized controlled trials with more than 4,300 participants suggested that taking 0.8 to 1.2 milligrams of folic acid per day might increase the risk of major adverse coronary events.

Prostate Cancer
A large study among 295,344 men found that men who take a multivita­min more than seven times per week and who also took a separate folic acid supplement had an increased risk of developing prostate cancer. A random­ized clinical trial of aspirin and folic acid supplementation for the preven­tion of colorectal cancer found that men taking folic acid supplements of 1.0 milligrams daily had a higher risk of developing prostate cancer over a 10-year period compared to those tak­ing a placebo.

Vitamin B12 – cyanocobalamin, hydroxocobalamin, methylcobalamin
Daily Maximum Recommended Intake: 2.4 micrograms

Vitamin B12 can cause diarrhea, blood clots, itching, hives and ana­phylaxis. Vitamin B12 at levels of 20 micrograms per day and pyridoxine at levels of 80 milligrams per day may cause intense redness of the skin with nodules, papules and pustules on the face and nose.

Vitamin C – ascorbic acid
Daily Maximum Recommended Intake: 90 milligrams

GI Effects
The adverse effects of oral vitamin C depend on the dose and include nau­sea, vomiting, irritation of the esopha­gus, heartburn, abdominal cramps, GI obstruction, flushing and diarrhea when several grams are taken at once.

Stones
Long-term intake of vitamin C may cause the development of stones in the urinary tract and kidney.

Heart Effects
A study in 573 middle-aged women and men who did not have the symptoms of cardiovascular disease found that supplemental intake of 500 milligrams of vitamin C daily for 18 months can cause a 2.5-fold increased rate of inner wall thickening of the carotid artery in nonsmoking men and a five-fold increased rate in male or fe­male smokers. In a study among more than 1,900 postmenopausal women with diabetes, intake of supplemental vitamin C was dose-related to in­creased risk of coronary artery disease and cardiovascular disease mortality.