Increasing Consumer Compliance

According to a 2003 report published by the World Health Organization (WHO), medical adherence rates in developed countries average an astonishing 50 percent. Adherence is a key factor associated with the effectiveness of all therapies, but is particularly critical for medications prescribed for chronic conditions. Of all medication-related hospitalizations that occur in the United States, it is reported that more than one-third are the result of poor medication adherence.

A recent article in the journal Mayo Clinic Proceedings (2011 Apr;86(4):304-14. DOI: 10.4065/mcp.2010.0575) suggested several solutions, such as encouraging a blame-free" environment, opting for less frequent dosing, improving patient education, and paying attention to rational non-adherence. The authors, however, forgot to address the manufacturers role.

For consumers suffering from chronic illnesses, the prospect of taking a daily regimen of softgels, capsules and tablets can be daunting, especially if they do not possess insurance coverage or have not met their deductibles. Equally important, more consumers are opting to deal with chronic disease states using natural products due to concerns about long-term pharmaceutical safety. Like drugs, consumers can also fail to comply with label recommendations.

For this ever increasing population, nutraceutical manufacturers can increase the adherence rate by providing physicians and consumers with formulations based on sound scientific research, an effective capsule design, use of the most bioavailable vitamins and minerals, proper inactive ingredients, sound product packaging and third-party lab testing, among other things. As the primary source of professional medical knowledge for consumers with chronic illnesses, physicians must play a key role in their education.

To design therapeutic formulations for different health states, using the right ingredients at the right dose means operating a formulation department that continually reviews scientific research published in the peer reviewed literature. This includes analysis of the studys experimental design and determining if the scientists conclusions are validated by the results of the research. It also means withholding final judgment until sufficient research has been conducted that is not contradictory and confirms outcomes from initial clinical trials.

An on-going evaluation of research is the best way of ensuring that manufacturers incorporate the proper dose for each ingredient, especially in special formulations that integrate a wide spectrum of vitamins, minerals and herbs. This means employing clinical nutritionists or chemists with terminal degrees in their respective disciplinesplus a commitment to reformulate when the medical research demonstrates a need for it. 

Proper formulation also means offering the most bioavailable forms, which can reduce the daily regimen of capsules that consumers need to take by delivering a higher percentage of the elemental vitamin, mineral and herb for absorption.

Not too long ago, bioavailability focused exclusively on minerals and the chelators chosen for each. As the National Institutes of Health (NIH) likes to demonstrate the concept, supplemental iron is available in two forms, ferrous and ferric, and ferrous iron salts are the best absorbed forms of iron supplements. Yet even here, the amount of elemental iron available in a supplement varies: for ferrous gluconate, it is 12 percent, for ferrous sulfate, it is 20 percent, but for ferrous fumarate it increases to 33 percent, or two-and-a-half times that for ferrous gluconate. Chelation clearly matters, and amino acid chelators have been found to be the most efficient at providing consumers with the greatest elemental amount of any mineral. For this reason, manufacturers should be using amino acid chelatorsunless so much space is consumed that it becomes physically untenable for inclusion.

In the past decade, though, it has been vitaminssuch as A, B and Ethat have had new forms developed to increase bioavailability to a significant degree, and thus may help improve medical outcomes. The B vitamins are the most dramatic in this regard. Water-soluble thiamin was the form traditionally used for B1, which is involved in glucose control and the breakdown of amino acids. Today, manufacturers can use benfotiamine instead, a lipid-soluble form of thiamin, and increase B1s bioavailability 3.5 times over that of thiamin. 

More significant is B9, for which manufacturers have traditionally used folic acid. However, not everyone converts folate to its biologically active form called 5-methyltetrahydrofolate (5-MTHF). Research shows that in a large proportion of the population, genetic enzyme deficiencies prevent the conversion of folate to 5-MTHF, leaving many vulnerable to low blood folate levels and higher than desired homocysteine. Now, however, manufacturers can provide the active form of folate in supplements. 5-MTHF is up to seven times more bioavailable than folic acid, and unlike folic acid, it can cross the blood-brain" barrier to enhance the synthesis of acetylcholine in the brainthe neurotransmitter associated with memory. Plus, it wont mask a B12 deficiency like folic acid.

Cyanocobalamin is the most frequently used type of B12 in the United States, but it is an inactive form that must be metabolized in the liver to methylcobalamin, and many people with B12 deficiencies have defects in digestion, absorption or metabolism. Recent evidence also suggests that methylcobalamin is superior, especially for neurological disease. This is because methylcobalamin bypasses several problems in the B12 absorption cycle and doesnt need to be decyanated. On top of that, methylcobalamin provides the body with methyl groups that play a role in biological processes important to overall health.

Inactive ingredients are equally important. Take magnesium stearate, an FDA approved natural excipient that helps with ingredient flow during the production process. Despite the small amount used per capsule manufacturing, this type of additive may compromise bioavailability by interfering with product dissolution and thereby impede absorption. Another natural excipient, ascorbyl palmitate, can be used to help guarantee the fullest bioavailability of vitamins, minerals and herbs without resorting to synthetic flow agents such as di-calcium phosphate.

In a related vein, some consumers  may look at supplement facts and refuse to buy the product for non-scientific reasons. Lets say it contains PEG, or polyethylene glycol, which is used as an inactive ingredient for film coating tablets and capsules. PEG is also widely used as an active ingredient in laxatives, oven cleaners and anti-freeze, so its presence may provoke an intense reaction in users who cannot differentiate between the inactive and active forms.

Manufacturers also need to deal with the fact that 10 percent of adult Americans suffer from dysphagiathat is, difficulty swallowingespecially older adults most likely to be suffering from chronic illness.  The presence of $5 pill cutters in pharmacies is prima facie evidence that we are still not paying sufficient attention to this issue. Hard-shell gelatin capsules are much easier to swallow than tablets and softgels that are oval, round, or too thick to navigate the esophagus cleanly. Of course, manufacturers also have the options of rendering nutraceuticals in chewable, liquid or powder forms, which enable patients to mix them with soft foods or beverages to accommodate their physical handicap. By the way, some herbs that may help improve swallowing include oil of peppermint and licorice.

In the vital area of production, all manufacturers should adhere strictly to cGMP (current good manufacturing practice) regulations, but also operate a robust QA/QC (quality assurance/quality control) program to carry out objective testing of ingredient identity and potency.  At the same time, manufacturers need to package supplements in containers that protect against environmental change and ensure product freshness since vitamins are sensitive to light, heat and oxygen. For this reason, nutraceutical manufacturers should think about packaging their supplements in amber-colored glass bottles rather than in plastic containers, which carry the risk of chemical leaching over time.

Any of these suggestions may appear minor in themselves, but committing to the execution of most of these critical elements will help increase medical adherence by consumers with chronic illnesses. It is part of a long-term relationship that must be nurtured.