Supplements: Food, Special Formulas, Pills, and Intravenous Infusions

Supplement Information Is Confusing


Broadcast and print media, the Internet, product information, and scientific literature frequently contain statements concerning supplements. The audiences span the full spectrum of demographics, and yet their common reaction to these statements is that they are receiving mixed messages. The lack of data needed to address the issues being discussed is one of several sources of confusion that will require great effort to eliminate. However, one source of confusion could be greatly reduced today if each statement concerning supplements always defined specific parameters, which should be available from the study on which the statement is based. Elimination of this source of confusion requires that the creators of all types of information concerning supplements define these parameters or that their audiences ignore information that does not include the needed definitions.

Compounds Are Presented to the Body in Many Ways
The same chemical compound may be both a nutrient and a drug. Niacin has long been recognized as an important nutrient in the diet that has been added to fortified flour, has been a component of daily vitamin pills, and has been used as a medication in many patients. Although all these uses of niacin are often termed supplementation, their effects on the recipient are not the same.

At the beginning of this century, compounds were presented to the body in the form of food.
With the discovery of the critical role of micronutrients in metabolism and the devastating deficiency diseases that result when the diet does not contain them in adequate quantities, vitamin supplements began to be presented to a large number of recipients. Complete liquid formulas for infants not receiving breast milk and complete liquid low-residue formulas for the space program were developed. Using this technology, researchers developed complete formulas and new enteral methods of presentation using tubes for patients who for medical reasons could not consume a diet in the usual manner. Today, messages from the public media suggest benefits for many healthy adults who consume some of these complete formulas as a supplement to their usual diet. During the last third of this century, special formulas and administration techniques were developed to permit total parenteral nutrition for many years in individuals whose gastrointestinal tract either was nonfunctional or had been surgically removed. Thus dietary compounds or nutrients are being presented to the body in many ways.

A growing body of data suggests that a compound required in the diet at a certain quantity to prevent well-described deficiency diseases may be presented to the body in higher quantities to prevent or to treat other undesired conditions. Therefore, the compound of interest has been added (in quantities greater then frequently consumed by healthy populations) to presentations known as functional foods, megadose vitamins, complete formulas for specific diseases, oral drugs, and intravenous drugs.

Table 1 lists the different modes of presentation used to “supplement” a recipient with compound C. Clearly the same compound is being presented by different routes, in different matrices, and in different quantities to recipients who are in different physiological states. However, each of these presentations has been termed C supplementation. It is not surprising that statements concerning C supplementation based on these different presentations of C and the accompanying different effects on the recipient do indeed give their audiences mixed messages.

Carnitine
This discussion is applicable to many compounds, but because my colleagues and I have studied carnitine for nearly 25 years, it is used for illustrative purposes. Carnitine biosynthesis in the body requires two essential amino acids and several essential micronutrients. Dietary carnitine is found predominately in animal products and is known to facilitate beta-oxidation of long chain fatty acids by transporting the fatty acids into the mitochondrial matrix where the enzymes of beta-oxidation are located. However, many other functions of carnitine are being investigated, and some of these may be more critical to many recipients receiving carnitine supplementation than its role in facilitating fatty acid oxidation. Exogenous carnitine is not required by healthy adults to maintain health and thus is not considered an essential nutrient. However, carnitine is being vigorously investigated as a conditionally essential nutrient because exogenous carnitine does appear to be required during certain physiological conditions such as during the newborn stage and during a variety of pathologies. The evidence that carnitine is a conditionally essential nutrient for the newborn led infant formula manufacturers more than a decade ago to add carnitine at concentrations found in breast milk to formula not containing endogenous carnitine. However, none of the Parenteral nutrition solutions available in the United States and frequently used in preterm neonates contains carnitine. Vegan diets contain little or no carnitine. The typical U.S. diet contains less than 5 mg/day of carnitine, but many patients receive 100 mg/kg per day of exogenous carnitine. Pharmaceutical grade carnitine is commercially available in the United States for both enteral and parenteral administration. The Internet and the print media currently advertise a multitude of products that contain carnitine with the suggestion that carnitine supplementation is beneficial to many different types of people. A large portion of these advertisements suggest that carnitine will either enable the recipient to lose weight or to improve physical performance.

Route of Presentation
A compound presented to the body via the gastrointestinal tract will be absorbed by a completely different mechanism than one presented to the body intravenously. However, other differences in metabolism of the compound may occur if the orally ingested compound is metabolized by enterocytes or metabolized during its first pass through the liver. Several amino acids that are not essential in an oral diet become essential during parenteral nutrition. Drugs administrated orally or intravenously do not demonstrate the same pharmacokinetics with both routes of administration.

Matrix of Presentation
The absorption and metabolism of a compound may be significantly altered by the presence or absence of other compounds. There are many well-documented examples of the absorption of a micronutrient being decreased or increased by the chemical composition of the liquid consumed with the micronutrient. For example, the iron in a serving of liver will be absorbed quite differently from the iron in a vegan diet. Also, the iron in an iron supplement capsule will be absorbed quite differently if it is taken at breakfast with a cup of tea or with a glass of orange juice. Food, complete formulas for specific disease states, and oral pills clearly present a compound to the body in very different matrices. However, the data from one of these presentations are frequently used to suggest what should be expected from one of the other presentations.

Quantity of Compound Presented
Carnitine is transported across the gastrointestinal tract by both active and passive processes, and the percentage of carnitine absorbed versus excreted is greatly modified by the quantity being presented to the gastrointestinal tract. In addition, metabolism of carnitine by the enterocytes appears to be altered by the quantity of carnitine being presented. A large number of studies have evaluated the potential beneficial effect of carnitine on symptoms such as anemia and exercise tolerance in renal patients on hemodialysis. Many questions remain unanswered including what quantity of carnitine should be presented. Some investigators have used quantities greater than those consumed in the diet of most populations with reasonably beneficial results, whereas other investigators have found that quantities closer to the amount consumed in the diet by many healthy populations to be more beneficial. However, the data from one of these presentations are frequently used to suggest what should be expected from one of the other presentations.

Purity of Compound Presented
If a 1-gram capsule of carnitine is not pure, there are two obvious potential problems. The recipient is not receiving the needed 1 gram of carnitine and is receiving an unknown compound, which may cause harm. Most recipients assume that any compound being administered to them is pure. For pharmaceutical grade compounds, there are required documented quality control checks to support that assumption, but these checks do not exist for compounds that are not pharmaceutical grade. As with many other compounds, the nonpharmaceutical grade carnitine products have been shown to vary widely in purity from 100 percent pure to undetectable levels. With some products, the capsules within a single bottle show varying levels of purity. However, statements concerning the supplementation of a compound such as carnitine often do not include any reference to the purity of the compound being used.

Physiological State of Recipient
One reason that compounds are presented to recipients in different quantities and matrices and by different routes is that the physiological states of the recipients differ; therefore, so do their needs. Even if one assumes that the preterm neonate, the child with an inborn error of metabolism, the renal patient on hemodialysis, and the weekend athlete would all benefit from exogenous carnitine, one would not expect their needs or their metabolism of the supplemented carnitine to be the same. However, the data from a recipient in one physiological state are frequently used to suggest what should be expected from supplementation of a recipient in a very different physiological state.

Suggested Approach
The following recommendation could be implemented today by the creators of all information concerning supplements.

Any statement concerning supplementation with a compound should define route of presentation, matrix of presentation, quantity of compound, purity of compound, and physiological condition of the recipient.

References

1. Borum P. Carnitine in neonatal nutrition. J Child Neurol 1995;10(Suppl):2S25-2S31.
   
2. Borum PR. Should hemodialysis patients receive carnitine supplementation? Renal Nutrition Forum, 1995.
   
3. Millington DS, Dubay G. Dietary supplement L-carnitine: analysis of different brands to determine bioavailability and content. Clin Res Regul Affairs 1993;10:71-80.