When You Take It Changes the Medicine

When I make up a herbal prescription and say "take this one in the morning, this one before bed," some people ask me back: "Does that really matter that much?"

The old books recorded dosing times quite carefully. For a long time I read that as experience hardened into rules. But going through the material on chronobiology, it struck me that the ground those rules stand on may be firmer than I had assumed.

The body has a clock — not as a metaphor, but in genes

The cells of our body actually contain genes that work as a clock. Following day and night, proteins accumulate and are broken down over and over, generating a daily cycle.

This is not a hypothesis. The researchers who worked out how this clock mechanism operates received the 2017 Nobel Prize in Physiology or Medicine, and it now belongs to the basics of biology.

Up to here, many people know. What is interesting is what comes next.

The path a medicine travels changes all day long too

There is a study that analysed human tissues on a large scale. Data from 13 tissues, 632 people.

About 7,500 genes were rising and falling on a daily cycle, and of those, 917 were drug targets, or transporters that carry drugs, or enzymes that break drugs down. More than 2,700 medicines are linked to these genes.

What this means is that the very path a medicine travels through the body is in a different state in the morning and in the evening. The route by which it is absorbed, carried, broken down and cleared.

Put the same medicine, at the same dose, in at a different hour — and the body handles it differently.

An experiment that changed only the arrival time

Let me give one thing that has been confirmed in people.

People with rheumatoid arthritis suffer from stiff joints in the morning. But this stiffness does not arise suddenly in the morning. Inflammatory signalling substances rise between two and seven in the small hours, and the result shows up in the morning.

So researchers tried this. The drug was the same and the dose was the same, but the tablet was made to release at two in the morning. Take it before falling asleep and it is released in the small hours.

In a double-blind trial of 288 people, morning stiffness fell clearly. The group taking the same drug in the usual way showed almost no change. Statistically it was significant by a narrow margin, and it is a single trial, but I like this design. They did not change the drug, and they did not increase the dose — they changed only the arrival time.

That people have long talked about pain worsening in the small hours and in winter is probably not unrelated to rhythms like this. (When it gets especially worse in winter and at dawn)

But it is not true of every medicine

There are medicines for which the hour is decisive, and medicines for which it hardly matters. With blood-pressure medicine, for instance, there have been cases where taking it in the morning or the evening made no difference to the outcome. It has to be weighed medicine by medicine, illness by illness.

So please do not move the timing of the medicine you are currently taking on your own after reading this. With some medicines the dosing interval itself is directly tied to safety. If you feel an adjustment is needed, please ask first at the place that prescribed it. (Is it all right to take herbal medicine and prescription drugs together)

The bacteria living in your gut have a rhythm too

There is one more interesting thing. There is research showing that the bacteria living in our gut also change in composition and in what they do over a daily cycle. A rhythm arises in step with mealtimes. This is still at the animal-experiment stage.

The reason this caught my eye is that among the compounds in herbal medicine there are ones that only work once the gut bacteria have opened them. (The medicine your gut has to switch on)

If the bacteria holding the key have a rhythm, then whether the hour you put the medicine in matches the time that key turns well could be a variable as well. This far is still my own conjecture. I have not seen a study showing in people that "therefore herbal medicine should be taken at such and such an hour."

I ask what time of day it gets worse

I ask when in the day the symptoms get worse. Whether it is stiffness in the morning, giving way in the afternoon, waking in the small hours. This is not simply history-taking, it is information. It tells me where in the body's rhythms the shaking is. (What time does in a long-standing illness)

And I set the dosing times together with you to match. If it is an hour that is hard to keep, please say so. There is no point fixing an hour you will not be able to keep, so it is better to set it again to fit your circumstances.

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When you take it is not a trivial matter. Because the body is not the same body all day long.

I no longer see the dosing instructions written in the old books as custom. I see them as a record of observation. Though observation is not the same as proof, so I am checking them one at a time.

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References

• An analysis of 13 human tissues and 632 people — drug targets, transporters and metabolic enzymes vary on a daily cycle — Science Translational Medicine, 2018
• A double-blind trial changing only the release time to the small hours, with the same drug at the same dose — Lancet, 2008
• How the biological clock genes work — the 2017 Nobel Prize in Physiology or Medicine — NobelPrize.org

Written by Dr. Heo Ji-young (PhD in Korean Medicine Pathology, Kyung Hee University · former Research Professor of Herbology, Kyung Hee University)