The Professional’s Guide to Nutritional Supplements: Understanding Quality and Regulatory Issues

| October 20, 2010

by Jacqueline Jacques, ND

Dr. Jacqueline Jacques is a Naturopathic Doctor with more than a decade of expertise in medical nutrition. Dr Jacques has spent much of her career in the dietary supplement industry as a formulator, speaker, writer and educator. She is the Chief Science Officer for Catalina Lifesciences LLC, a company dedicated to providing the best of nutritional care to weight loss surgery patients.

Abstract
Most weight loss surgery programs in the United States recommend dietary supplements as part of their postoperative care. Health professionals are often confused about the regulatory and quality issues in the dietary supplement industry. This article reviews the current regulatory status of dietary supplements in the United States in an effort to help clinicians better evaluate products they recommend for their patients.

Introduction
Most weight loss surgery (WLS) programs in the United States recommend dietary supplements as part of their aftercare program. Health professionals are often confused about the regulatory and quality issues in the dietary supplement industry, which may lead to difficulty in evaluation of what products are safest and most reliable to recommend for patients with malabsorption. This article reviews the current regulatory status of dietary supplements in the United States in an effort to help clinicians better evaluate products they recommend for their patients.

Dietary Supplements
It helps to start by understanding what a dietary supplement is and is not. Dietary supplements were defined in 1994 by Congress under the Dietary Supplement Health and Education Act (DSHEA). Under DSHEA, a product is a dietary supplement if it does the following:
1.    Intended to supplement the diet

2.    Contains dietary ingredients, such as vitamins, minerals, herbs (other than tobacco), amino acids, other natural substances, and/or their constituents

3.    Ingested orally in the form of a pill, capsule, tablet, or liquid
4.    Labeled on the front panel of the product as a dietary supplement
5.    Sold and marketed as a dietary ingredient before October 15, 1994, or has been approved by the United States Food and Drug Administration (FDA) as a new dietary ingredient (NDI)
6.    Intended use is as a dietary supplement, not as a food or a drug.

Supplement versus drug?
Some substances are sold as both supplements and drugs. For vitamins, minerals, herbs, or other natural dietary ingredients, the intended use, language used to describe the product, or route of administration can be the defining point. Per the FDA, dietary supplements may not be used to or claim to diagnose, cure, mitigate, treat, or prevent a disease; substances that do this, or claim to do so, are drugs.

Niacin is a great example of a nutrient that is both a drug and a dietary supplement, depending on the language used to describe it. Niacin is available both as a prescription drug and as a dietary supplement. For niacin products (such as Niaspan®) that are approved as drugs, companies may state that niacin can improve cholesterol and lower triglyceride levels. For niacin products sold as dietary supplements, companies may state that niacin supports a healthy cardiovascular system or helps to maintain cholesterol levels that are already within the normal ranges. It is not allowable for the supplement companies to discuss the ability of niacin to alter cholesterol and triglycerides, despite this being an established drug activity; they must stick to structure-function claims (see below). If a supplement company states that their niacin lowers cholesterol, it then becomes an unlicensed drug and the company may be subjected to fines or other penalties.
Route of delivery can also turn a dietary supplement into a drug. As stated above, dietary supplements must be orally ingested as pills, capsules, tablets, or liquids. They cannot be sprayed into or on the body; they cannot be applied as a cream, gel, or patch; they cannot be inhaled, sprayed into the nose, or dropped into the eyes; and they cannot be injected subcutaneously, intramuscularly, or intravenously. Substances delivered by these methods, without exception, are drugs, not dietary supplements.

Medical Food
A lesser used category of natural products are those considered by the FDA to be medical foods. Medical foods are technically regulated under the Orphan Drug Act, not DSHEA. This means that they are not dietary supplements. Medical foods are defined as specialized dietary products that are not available for sale to the general public and must be supervised by a physician. (Some, however, are now being sold in pharmacies, and infant formulas—which are technically medical foods—are sold in mass retail.) The intent of medical foods is to manage a specific disease or condition. They must also meet the following criteria:
1.    They are intended to be used in patients who, “because of therapeutic or chronic medical needs have limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or who have other special medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone.”
2.    They are formulated for the partial or exclusive feeding of these patients, whether by oral intake or use with a feeding tube.
3.    They provide nutritional support for unique needs created by a unique medical condition.
4.    They are intended to be used only under medical supervision by patients requiring ongoing care that includes instruction on use of the product.

An example of a medical food would be phenylalanine-free foods for people with phenylketonuria (PKU) or gluten-free foods for those with celiac disease. At this point in time, there is very little FDA oversight of these products and associated claims, and most people in the dietary supplement industry consider this to be a loophole in the FDA regulation of natural products. Unscrupulous companies see this as a way to sell products using drug claims that are not allowed under DSHEA and still avoid oversight. Like dietary supplements, it is not necessary for medical foods to be submitted to the FDA for approval prior to sale. Unlike dietary supplements, they may claim to treat or assist with disease states. Medical foods are also exempted from the Nutrition Labeling and Education Act (NLEA) that governs claims on food ingredients. Many industry experts consider it likely that the FDA will begin stricter oversight of medical foods in the near future. For the time being, however, while this law allows for the development of much needed dietary products for individuals with rare disorders and special needs, it also permits products that should be dietary supplements or drugs to come to market without much, if any, regulation.

Regulatation of products and the industry

There is a general misconception that there is no federal agency with authority over the dietary supplement industry. In fact, the FDA has always had this authority, but the degree to which they have exercised it has changed much over the years. The FDA has had official authority over dietary ingredients since the passage of the 1938 Food, Drug, and Cosmetic Act. The 1994 passage of DSHEA merely created a new category and specific regulations for the industry to separate it from both foods and drugs.

Manufacturing oversight. The question of manufacturing quality and oversight for dietary supplements has been one of much debate both inside and outside of the industry. DSHEA authorized (but did not require) the FDA to create Good Manufacturing Practice (GMP) guidelines as it has in the past for the pharmaceutical industry. This was largely ignored for the better part of a decade. In the ensuing years, companies were required, as they had been for decades, to comply with food GMPs that essentially govern safety and sanitation. Industry groups, such as the National Nutritional Foods Association, created their own GMPs and associated certifications to help those who wished to comply with some standard. Some manufacturing facilities attained or retained status as OTC drug manufacturers, subjecting themselves to FDA GMP audits, but since none of these things were required, oversight was inconsistent at best.
In 2007, the FDA formally adopted GMPs for the dietary supplement industry. Phased in over a three-year period to allow smaller companies to comply, as of June 2010 companies of all sizes must be able to demonstrate operation under these guidelines.
The federal GMPs regulate the activities of manufacturing, packaging, holding, and distributing of dietary ingredients and dietary supplements in a manner that assures that products cannot be adulterated or misbranded. They further require manufacturers to evaluate the identity, purity, quality, strength, and composition of their dietary ingredients and dietary supplements by means similar to those required for the pharmaceutical industry. In their review of the industry prior to publication of proposed GMPs, the FDA noted multiple issues of concern, including substitution of incorrect ingredients (in some cases dangerous); use of non-food grade ingredients and chemicals in manufacture; product contamination with organisms such as Klebsiella pneumonia or botulism; contamination with lead and glass; unsafe and unsanitary manufacturing conditions; products containing levels of nutrients that do not match label claims; undeclared ingredients, such as potentially harmful allergens; lot-to-lot variability in product consistency; and other problems. It is the hope of both the FDA and industry leaders that the enactment of GMPs will bring safety and quality to all areas of the industry, allowing for a significantly increased confidence in natural products.

Those who wish to read more about the federal GMPs can do so at the FDA website: http://www.fda.gov/
Food/DietarySupplements/default.htm

Product oversight. The FDA requires drugs to undergo premarket studies to establish safety, efficacy, dosing, interactions, and other specified parameters before their products are approved for sale. No such testing and approval is required for dietary supplements. However, the FDA does have oversight over manufacture, labeling, claims, and safety of dietary supplements.

As far as safety goes, the FDA currently treats dietary supplements more like foods than drugs. This means that companies selling dietary supplements are responsible for their safety, and the FDA is responsible for demonstrating that a product is unsafe before it can restrict use or recall the product from the market. Since 2006, any company with their name and contact information on their product is also required by law to log and document product complaints and adverse events. Serious adverse events (SAEs), such as birth defect, serious disability, hospitalization, or death, must be reported to the FDA in a standardized fashion very similar to that used for medical devices (in fact, the same form is used for both). The good news is that reporting seems to be demonstrating that most supplements are very safe. The FDA had estimated that they would receive 960 event reports per year, but in 2008, they only received a total of 604 reports. By contrast, in the same year the FDA registered 482,154 adverse events for prescription drugs.

The FDA regulates labeling for dietary supplements as it does for foods. Since the passage of DSHEA, the FDA has operated the Office of Nutritional Products, Labeling, and Dietary Supplements through the Center for Food Safety and Applied Nutrition (CFSAN). The FDA cites the purpose of this office as “monitoring safety, e.g., dietary supplement adverse event reporting, and product information, such as labeling, claims, package inserts, and accompanying literature.” It has been the role of this office to attempt to clarify and make uniform the manner in which companies manufacturing and distributing supplements communicate to the public. Additionally, there has been increasing regulation of the way label information is conveyed (in the hopes of making it easier for consumers to understand), as well as requirements for full ingredient disclosure (including excipients, binders, fillers, encapsulating and coating materials, and allergens).

Advertising and claims
The FDA and the United States Federal Trade Commission (FTC) technically work together to regulate what is said about dietary supplements. Where the FDA has primary jurisdiction over things that are on the product—the label, the packaging, inserts, and appended literature—the FTC has oversight over commercials, internet marketing, print media, catalogs, and direct marketing materials.
Product claims. The issue of claims made about dietary supplements is perhaps most irritating to physicians and confusing to consumers. As discussed above, the FDA and the FTC both have some oversight over claims, packaging, and label information. However, it seems that between these two agencies, they still struggle to maintain control over inconsistent, unproven, and just plain false information being distributed to consumers. This problem clearly has been compounded by the internet, which we now know is used by approximately 16 percent of the United States adult population to seek out information on health. In the September 17, 2003, issue of Journal of the American Medical Society, Morris and Avorn conducted a survey of health claims made on the internet about the most common dietary supplements. The reviewers looked at 443 websites and applied FDA criteria to classify claims as “disease” or “non-disease” in nature. Of the surveyed sites, 76 percent were retail sites either selling product or directly linked to a vendor. Of this 76 percent, 81 percent (338 sites) made one or more health claims, with 55 percent of these claiming to treat, prevent, diagnose, or cure specific diseases. Moreover, 52 percent of retail sites failed to include the mandated federal disclaimer for dietary supplement sales. Only 12 percent of sites provided any reference materials to support claims. Thus, the authors concluded that despite supposed FTC authority to regulate these materials, the current enforcement of claims (at least on the internet) is quite poor and likely to mislead consumers.

By law, allowable claims for dietary supplement are supposed to meet both FDA and FTC criteria. The FDA offers general guidelines for structure-function claims, language for approved health claims (very limited), and required disclaimers (such as those that caution use in pregnancy and nursing). The FTC further offers guidelines for advertising that are designed to assure that materials are truthful and not misleading in nature. They further require claims to be adequately substantiated by solid scientific data.

Details of what the FDA requires can be accessed at http://www.fda.gov/Food/DietarySupplements/DietarySupplementLabeling/default.htm; FTC requirements are available at http://business.ftc.gov/docu
ments/bus09-dietary-supplements-advertising-guide-industry.

It may be easiest to understand the difficulty with these regulations by exploring real examples. Calcium is a nutrient that works well for this purpose. Most of us would likelyagree that calcium is an important part of strong bones and that adequate intake helps to prevent, and perhaps even treat, bone loss. The FDA allows the nutritional supplement industry to use the following claim:
“Regular exercise and a healthy diet with enough calcium helps teens and young adult white and Asian women maintain good bone health and may reduce their high risk of osteoporosis later in life.”

Many nutritional companies have shunned this allowable claim due to its restrictive nature and have instead chosen to use structure-function language that might read something like: “Calcium helps to support healthy teeth and bones.” Still other companies may ignore all guidelines and opt to make claims that calcium, or their calcium in particular, prevents osteoporosis or even that it treats or prevents a broad range of other conditions, such as cancer or diabetes.

Bariatric professionals should also be aware that the FTC has placed specific emphasis on products and companies that market products for weight loss. Following a 2002 FTC report that found more than half of the advertising for products and services for weight loss contained false or unsubstantiated claims, the FTC began increasing oversight specifically targeted at this industry segment. In 2003, the FTC began a campaign called “Red Flag,” which gave guidelines to media on how to spot false advertising of weight loss products. Subsequently in 2004, they launched “Operation Big Fat Lie,” which levied aggressive fines against some of the biggest companies with misleading advertising. Still, not all companies comply with advertising rules, and many of these companies are starting to see both pre- and postoperative weight loss surgery patients as a rich source of revenue. Patients should be counseled on what products are both safe and effective to use both before and after surgery. Health professionals may additionally want to advise them of how to spot false claims. This information can be viewed on the FTC web site at: http://www.ftc.gov/bcp/menu-health.htm, under the “Business Information” section.

My general advice to health professionals and patients alike is that claims for a product should not be taken at face value, companies should be able to produce substantiation to support any claims made, and that if it sounds too good to be true it probably is!

Quality of ingredients
Ingredients in dietary supplements—from vitamins to herbs—come from all over the world. While some ingredients are domestic, many come from China, India, and third-world nations where controls on processing may not match those in the United States or Europe. Again, the manufacturing GMPs should help to diminish or eliminate the use of questionably sourced raw materials in manufacture by requiring more independent testing of raw materials, microbial screening, quarantine, and other quality controls.

Manufacturers can choose from a variety of sources, forms, and grades of nutrients. The current accepted standards for most nutrients follow the guidelines set out by the United States Pharmacopoeia (USP) and National Formulary (NF). These standards exist for over 2000 ingredients. The FCC (Food Chemical Codex) writes standards for substances commonly used as excipients. All of these designators (USP, NF, FCC) may appear on labels of products if manufacturers and distributors choose to indicate that they are using certified ingredients, although they are often omitted due to space limitations. For some ingredients, especially herbs, there may be no standard set, and it is harder to judge from a label the quality of the ingredients. Additionally, some manufacturers may not supply this information on the label and it is then the responsibility of the consumer obtain it.

Nutrient forms
Both in nature and in supplements, nutrients can be present in a variety of forms. Some of these forms may have different activities in the body, may be more or less bioavailable, or may even have different levels of toxicity. Again, niacin makes a great example. Niacin is commonly found in two forms: niacin (nicotinic acid) and niacinamide (nicotinamide). Both of these substances are classified as niacin and vitamin B3, and are utilized in the body to form coenzymes. However, there are vital differences in their functions. The acid form is the only form demonstrated to lower cholesterol and triglycerides; it also causes flushing. The amide form will not lower blood fats or cause flushing. Since the amide form is most common in dietary supplements, physicians recommending OTC niacin for cardiovascular health would need to specify this for patients. All prescription forms of niacin use the acid form for this reason.

Another excellent example is vitamin E. The most common form of vitamin E found in nutritional supplements is synthetic dl-alpha-tocopherol (all-rac-alpha- tocopherol). Because one isomer making up half the mix is not usable by the human body, this form is not nearly as bioavailable as natural vitamin E. The natural form, d-alpha-tocopherol or RRR-alpha-tocopherol, is almost twice as bioavailable and is thus much preferred. Still, since consumers may not be familiar with the complex nomenclature, they may think that they are getting a high level of vitamin E in a product that really only provides half the labeled amount in a useful form. Similar examples can be seen for many vitamins and minerals, including calcium, iron, selenium, and thiamine.

Chew, swallow, or drink?
There are also many choices for how products are delivered. The most common forms are chewable tablets, liquids, hard-coated tablets, and gelatin capsules. Regardless of the way a product is delivered to the body, the quality of the ingredients is still of great importance. Despite what a manufacturer may say, merely putting something into a liquid medium does not give it 100-percent bioavailability—it just eliminates one level of work the body would have to do to break the product apart. The form of the nutrient itself, amount delivered, mechanism of absorption in the gut, nutritional status at the time of delivery, and other factors all play into bioavailability, so nothing is ever 100 percent. Hard-coated tablets pose the greatest potential challenge to WLS patients. Many of these preparations are designed to break apart with stomach acid and churning. Some will break apart without this, but it’s hard to know which ones. If you have a tried and true product in a coated tablet that you use, there is no need to change, but if patients are going on their own to find one at the store, it is probably not the best choice. Two-piece gelatin capsules are a great choice as they will break apart with moisture and heat and require no mechanics. Chewable products that are broken apart with the teeth and liquids can also be good choices so long as the ingredients are appropriate for WLS patients. With liquids, stability can be an issue and they should always be checked for an expiration stamp. Products with crystal formation or a lot of sediment should be suspect. The delivery system that you choose can also help with patient adherence. You may have a product you love, but if your patient cannot swallow it or despises the taste, he or she is not likely to stick with your recommendation.

Excipients, binders, fillers, and “other ingredients”
All dietary supplements contain other ingredients that are not active constituents in the product. These may include binding agents, flow agents, fillers, coating material, disintegrants, lubricants, granulating agents, colors, sweeteners, and in addition, it is common for these raw materials to include one or more additives themselves. For example, very small nutrients like folic acid are diluted to make them easier to mix and measure. Common diluting agents include calcium and lactose. Fat-soluble vitamins that have undergone an oil-to-powder process to make them compressible can have multiple additives, such as calcium, silicon dioxide, lactose, starch, gelatin, vitamin E, and preservatives. All ingredients, including those pre-mixed with raw materials, should be declared on the label of a product below the Supplement Facts box on the right panel. Allergen disclosure regulations that became active on January 1, 2006, require manufacturers to obtain allergen declarations from all raw material suppliers and properly disclaim allergens on product labels. Consumers with known allergens should be advised to closely read labels for this type of information and would be wise to call the manufacturer if there are any questions.

Conclusions
The dietary supplement industry is currently in a state of maturing. While regulations do exist and more are on the way, the problem of enforcement still looms large and makes it difficult for both consumers and medical professionals to evaluate key issues related to safety and efficacy. For now, the best assurance that physicians have if they recommend dietary supplements is to seek out products from manufacturers that can demonstrate that they operate under GMPs. In regards to advertising, it is important for physicians to recognize that their patients are likely to encounter many fraudulent or unsubstantiated claims when they investigate dietary supplements, and that they as health experts may be called upon to comment on these issues. Health professionals too should be aware that claims about products may not be backed by science that has been reviewed by any authority, and should take care to assess the science themselves before taking claims at face value.

As the industry of bariatric surgery continues to grow, the dietary supplement industry will focus more on these patients as a specific and potentially lucrative market. Helping patients to understand these issues is important to their long-term health, as well as to the long-term success of the WLS industry. The healthier patients are, the better it is for everyone. Clinicians working with bariatric surgery patients need to learn exactly what their patients are taking, encourage open lines of communication, seek information from product companies, and establish nutrition protocols that are based on sound recommendations.

Resources
1.    FTC Guidance Documents for Consumers and Businesses: http://www.ftc.gov/bcp/menus/resources/guidance/health.shtm
2.    FTC Weight Loss and Fitness Center: http://www.ftc.gov/bcp/menus/consumer/health/weight.shtm
3.    FDA Center for Food Safety and Applied Nutrition: http://www.cfsan.fda.gov/
4.    FDA Office of Nutritional Products, Labeling, and Dietary Supplements: http://www.cfsan.fda.gov/~dms/onplds.html
5.    FDA Med Watch Program: http://www.fda.gov/medwatch/
6.    National Institutes of Health Office of Dietary Supplements: http://ods.od.nih.gov/
7.    National Nutritional Foods Association (offering both GMP certification and product testing programs since 1999): http://www.nnfa.org
8.    NSF International (offers GMP certification, ISO certification, ingredient validation services to the dietary supplement industry since 2003): http://www.nsf.org
9.    United States Pharmacopeia (Offers the USP Verified program for both ingredients and manufacturing): http://www.usp.org
10.    A new dietary ingredient (NDI) is a vitamin, mineral, herb, amino acid, or a concentrate, metabolite, constituent, extract, or combination of any of the above dietary ingredients that was not marketed in the United States as a dietary supplement prior to October 15, 1994. These substances must be submitted to the FDA for approval a minimum of 75 days before they are made available for sale.
11.    US Food and Drug Administration, Center for Food Safety and Applied Nutrition. http://www.fda.gov/About
FDA/CentersOffices/OrganizationCharts/ucm135675.htm
12.    Tu HT, Hargraves JL. Seeking health care information: Most consumers still on the sidelines. HSC Alerts 2003;Issue Brief No. 61. http://www.hschange.org/
index.cgi?topic=topic03
13.    Morris CA, Avorn J. Internet marketing of herbal products. JAMA 2003;290:1505–1509.
The disclaimer is as follows: This (these) statement(s) has(have) not been evaluated by the Food and Drug Administration. This (these) product(s) is(are) not intended to diagnose, treat, cure, or prevent any disease.
14.    US Food and Drug Administration. Center for Food Safety and Applied Nutrition. A Food Labeling Guide. September 1994; Revised April 2008. http://www.fda.gov/Food/GuidanceComplianceRegulatoryInformation/GuidanceDocuments/FoodLabelingNutrition/FoodLabelingGuide/default.htm
15.    Traber MG, Elsner A, Brigelius-Flohe R. Synthetic as compared with natural vitamin E is preferentially excreted as alpha-CEHC in human urine: Studies using deuterated alpha-tocopheryl acetates. FEBS Lett 1998;437(1-2):145–148.

Funding: There was no funding for the development of this article.

Financial disclosure: Dr. Jacques is Chief Science Officer for Catalina Lifesciences LLC.

Editors Note: This article was excerpted from Micronutrition for the Weight Loss Surgery Patient by Dr. Jacqueline Jacques. Copyright © 2006 Matrix Medical Communications • 148 pages • ISBN 0976852624

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  1. patricia says:

    I WOULD LIKE TO BUY THIS FOOD DO YOU KNOW WHERE CAN BUY WHOLESALE TO RESALE IT ON THE INTERNET OR HOW I GO ABOUT IT