A pharmacist's perspective on health and metabolic disease
At high school, I can remember having a bit of a struggle with calculus, so my Dad (a marine engineer) was helping me out. The maths was a bit different to what Dad was familiar with, so as he tried to figure things out, he would repeat “If you are not sure of what is going on, go back to first principles….” I heard that phrase a lot, but it must have worked, because I passed the exams!
However, that phrase (“If you are not sure of what is going on, go back to first principles….”) has obviously stuck with me because not only did it help me get through my thesis, I now find myself saying it to my pharmacology students!
In the early days of my thesis, when my supervisor Prof Grant Schofield was first getting into LCHF we had some vigorous discussions because I was trained in the traditional thinking that high fat was bad. But I didn’t have enough evidence to fully refute what he was saying. After reading “The Art and Science of Low Carbohydrate Living” I had full on cognitive dissonance and didn’t know what to believe or even where to begin.
“If you are not sure of what is going on, go back to first principles….”
I went back to basics and pull out physiology and biochemistry textbooks (and wishing I had paid more attention to those lectures 20 years ago), to try and come to grips with what happens to different hormones with respect to food and different stimuli. But I am also a visual learner, so needed a picture, but as seems to be the case, I couldn’t find one that really answered my need, so got The Engineer to help draw me one. It seems that the principles of drawing physiologic control systems are very similar to that of circuit diagrams!
I used this image to try and work out which hormones were associated with appetite and energy regulation, but also, to a degree, where to stop looking. Because there was a poverty of knowledge on the subject at the time (this was before I came into contact with people like Dr Joseph Kraft, Ivor Cummins or Dr Jeff Gerber), I did have to both simplify and “ring-fence” my thinking.
I can’t remember why protein is missing from the body fuel process – either because I didn’t understand its impact on raising blood glucose levels, or because excess was converted to glucose. Looking at it now, maybe it could use another arrow from the brain to the pancreas to illustrate the parasympathetic stimulation, and another to indicate how blood glucose levels provide feedback to the pancreas…..and another…….
But I do remember that we deliberately chose not to put on feedback arrows to keep the image simple. For example, if this person was scared, the sympathetic nervous system would stimulate the adrenal glands to increase production of both cortisol and adrenaline. This would have the flow on effects of causing temporary down regulation of GLUT4 transporters, increasing insulin resistance, ensuring that there is sufficient glucose going to the brain, but also would perhaps increase hepatic gluconeogenesis, to ensure that there is sufficient glucose available. This would have the flow on effect of increasing insulin and so forth…… But, different stimuli, would have different flow on effects. I just had to keep visualising my own effects for each system changes.
This image stayed on my cubical wall throughout my PhD so each time I had to ponder a system change, I could look at this image and visualise what would happen to other parts of the system. But it was also a reminder to try and keep my thinking focused and go too deep or wide. I know a lot more now about insulin than I did then, but I had to start somewhere in the journey.
Back then, I was having a lot of trouble understanding what was going on, so I went back to first principles.