Drugs and your Metabolism

We’re all aware of our metabolism and whilst we may not have control over it, our metabolism may play a role in the effectiveness of, and side-effects from, certain medications. It isn’t one size fits all. Do we need to rethink how we deliver drugs?

We need energy to function, but we can’t plug ourselves in to the mains and recharge like our phones. Instead, we use the process of metabolism for essential energy conversion, changing the energy in food and drink (i.e. chemical energy) into energy we can use for countless functions such as growing and even breathing. During the metabolic process, ingested calories are combined with oxygen to release the essential energy we require. Our metabolic rate is dependent on the number of calories our body uses for basic functions (e.g. breathing, blood circulation, altering hormone levels, and growing and repairing cells). There are three main factors which determine your basal metabolic rate (BMR): body size/composition, biological sex, and age. The larger or more muscular an individual is, the higher their metabolic rate even at rest. On average, biological males have less body fat than their female counterparts, leading to more calories burnt at rest, and thus a higher metabolic rate. Finally, as you age, your muscle to fat ratio usually decreases, slowing down the rate at which you burn calories while resting. Your BMR can account for up to 80% of your body’s daily energy requirements, dependent on the above factors and lifestyle choices.

Whilst your basal metabolic rate is important, two other factors also contribute to the number of calories your body burns everyday: processing food in the body (i.e. thermogenesis, which includes digestion, absorption, transportation and storage) and physical activity. Only in rare cases are an individual’s weight gain linked to a slow metabolism, such as Cushing’s syndrome or an underactive thyroid gland. The most effective way to lose weight is to consume fewer calories than those you burn through physical activity: the more active you are, the more calories you burn. The NHS, and other health services, acknowledge that aerobic activity (such as walking, cycling, swimming etc.), strength training and generally being active are the best methods to burn calories as we have little to no control over our BMR.

What about the effect of our varied metabolisms on prescribed medication? Whilst we can control the number of calories we ingest and the amount of exercise we do, we cannot control our genetics. As with food and drink, when we take drugs orally they are metabolised (i.e. broken down) and the active ingredients are, hopefully, released at the correct time/point in our system. However, some research indicates that certain metabolic rates may lead to higher chances of side effects from medications. For example, if your BMR is slower, a drug may stay in your system too long causing side effects. Whilst an individual with a rapid metabolism may break down the medication too quickly, removing it from the system before it has had a therapeutic (beneficial) effect. Chemotherapy drugs are a prime example of how metabolism can effect their usefulness.

One way to potentially overcome varying BMRs is to deliver the active ingredient as a prodrug. A prodrug is defined as a “biologically inactive compound which is metabolised in the body to produce the active drug“. Here, chemists mask the active drug, preventing it from acting too early. One example of how prodrugs could be used effectively is in chemotherapy, which has notoriously horrible side-effects. Such side-effects, like hair loss and damage to healthy cells, are caused when the chemotherapy drug targets any rapidly dividing cells it encounters. Obviously, this is great for destroying or preventing the replication of cancerous cells, but not specific enough to avoid damage to healthy replicating cells. By masking the active drug, scientists can attempt to target more specific environments in which cancer cells reside so the prodrug is metabolised to the active form at the correct point, avoiding more healthy cells. Such prodrug methods were discussed at the Cancer Chemotherapy and Drug Metabolism symposium in 2005 (you can read the full report HERE), namely the use of hypoxia-activation. Unlike healthy cells, cancerous cells create a low-oxygen (hypoxic) environment. Prodrugs which are only metabolised in such environments would avoid many healthy cells once the active drug is released, leading to fewer side-effects.

Finally, there is still the potential for personalised medicine. Whilst personalised medicine has many pitfalls to overcome before they could be used in the general population, to prescribe someone medication based on their genetic makeup (including their BMR) would revolutionise pharmaceuticals. While we cannot control our BMRs, further scientific advances into how our individual metabolisms and genetic sequences influence reactions to medications can hopefully lead to better futures, especially those needing treatments such as chemotherapy.

While you’re here:

If you want to know more about how external factors can influence our genes and one day lead to personalised medicine, read my previous article about epigenetics with the link below.

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