Recently a study that was published in the prestigious Proceedings of the National Academy of Sciences (PNAS) discussed how B vitamins (specifically folic acid, B6 and B12) may be able to slow the development of Alzheimer’s disease, slowing the shrinkage of brain volume (Douaud et al. 2013). This is not the first study of its kind, but is one piece of the mounting pile of evidence that suggests that one of the biggest causative factors of Alzheimer’s is elevated homocysteine levels, and that controlling homocysteine may be a viable treatment. It all started over 15 years ago, with the observation
We constantly hear and read the term bioavailability thrown around in pharmacological and nutritional sciences. But what does it mean when a product has high or low bioavailability? Why is it important, and what factors contribute to this?
Definition of bioavailability
While there are slight differences in the usage of the term between pharmacology and nutritional sciences, bioavailability is essentially a measure of the extent and rate at which a product enters systemic circulation. Simply put, bioavailability is the amount of an ingredient that gets absorbed in the body. When products are administered intravenously, they are fully available in the blood stream and are 100% bioavailable.
However, when compounds are administered via other routes, such as orally, the overall percent bioavailability varies as these drugs must pass through further barriers before reaching systemic circulation. In order to become bioavailable, products must survive the acidic environment of the stomach, pass through the intestinal wall and then the portal circulation to the liver. At the liver, many products are metabolized, and many products may not even reach circulation. As such, oral bioavailability is one of the most important properties in drug design and development.
For a product to be effective, it must be bioavailable, though the window of therapeutic effect may greatly differ from product to product. Many antibiotics such as penicillin have wide therapeutic index, thereby rendering any small changes in bioavailability negligible. However, there are many drugs on the market that have a very narrow therapeutic index, and developing product formulations that increase bioavailability are key to the success of these products.
Physical and chemical characteristics that effect bioavailability
The chemical and physical characteristics of the product, as well as product formulation are all critical factors that must be considered for increased bioavailability. The dosage forms (solid, liquid or gas) are all important in determining bioavailability. In general products that are in liquid form have higher bioavailability than products in a solid form. This is one of the key reasons softgels offer superior absorption that tablets or capsules. Tablets and capsules (which are both in the solid state) must first become soluble before absorption can begin. On the other hand, softgels are already in a liquid state and therefore ready for absorption!
In addition, small particles are more readily absorbed than larger particles. Products that are poorly soluble (hydrophobic) or highly charged are likely to be poorly absorbed in the gastrointestinal (GI) tract. The manufacturing method as well as product formulation also influence bioavailability. Products may be delivered alongside inhibitors that will prevent fast metabolism or can increase absorption.
Other factors of the body that may reduce bioavailability include insufficient time for the GI tract to absorb the product, digestion by enzymatic proteins, metabolism by the GI flora (or any other factor relating to health of the GI tract), time of the day products are administered, whether or not products are taken with food, or disease state of the individual. As such, there can be great variability from person to person.
Low oral bioavailability in clinical trails is a major reason for many drug and product candidates failing to reach the market. Animal experiments are routinely set up prior to starting human clinical trials. Though, whether or not these animal trials are a reliable estimate of human response is a debatable topic….
As you can see, there are a lot of factors that must be considered in product design!