Metabolic Imbalance

Metabolism is the process by which we convert the food we eat into energy. Healthy metabolism is a balance between nutrition and energy expenditure. The human journey can be thought of as a taming of this process in an eternal struggle to acquire more nutrients to support our energy needs. Our capacity to evolve such a large brain is likely attributed to being capable of harnessing more energy from our foods. Living organisms have evolved this process over 3 billion years through ice ages, droughts, and other famine conditions. The evolution of our metabolic process involved genetic variations as well as behavioral modifications that enabled us to fight these periods of food scarcity and survive. But little did we know, we may be the dog who chases its own tail… and catches it.

Twice of the past 65 million years there have been mutations in animals that enhanced the ability to convert fructose (the sugar in fruits) to fat. These mutations to enhance our nutrient storage likely set the evolutionary stage for selecting for the greater brain size and its extremely high metabolic demands. This first mutation established fructose as the dominant sugar that has mechanisms to make it very efficient at converting and storing it in the form of fat. The tremendous advantage of this mutation was its ability to allow animals to engorge themselves on fruits and honey during times of plenty, store that food in the form of fat and during periods of scarcity that animal could survive off that fat. The second major mutation occurred approximately 12 million years ago, in uric acid metabolism of European apes. When fructose is metabolized (in the liver, kidneys, pancreas, intestines, muscles, brain and fat cells) it is brought into those cells where it then steals energy, in the form of phosphate molecules, from our energy currency called ATP. It will continue to steal phosphate molecules from ATP→ADP→AMP→→uric acid. As the phosphate in the mitochondria gets stolen by fructose, that low level of phosphate activates an enzyme which converts AMP ultimately to uric acid. This pathway of converting AMP to uric acid is only seen with fructose metabolism and not seen with glucose metabolism. The mutation 12 million years ago stops or slows any further processing of uric acid allowing it to build up in the system. The consequence of that uric acid buildup are many fold:

• With less energy in the liver there is greater lethargy and less energy exertion. The body thinks it’s going into a period of starvation due to the lack of energy and it prepares for hibernation and food
• With less exertion there is less energy expenditure by the other tissues so glucose will build up in the
• The inflammation produced from uric acid creates insulin resistance and reduces glucose metabolism
• The oxidative stress from uric acid buildup in the liver as well as elevation of blood glucose inhibits the burning of fat and promotes its storage, in the liver, pancreas and other visceral organs
• When uric acid builds up in the kidneys it produced high blood pressure and when it builds up in other organs it generates oxidative stress (inflammation) which damages that organ
• To make matters worse, when glucose levels get high in the liver there is a pathway that gets turned on called the Polyol Pathway that begins to convert glucose (and alcohol) into sorbitol and then into fructose, which only starts this cycle all over again

Continuing on our evolutionary path, it was approximately 2 million years ago when our ancestors started to capture more of the nutrients from our food through cooking with fire. 22,000 years ago is the first evidence of humans showing another means to capture more nutrients from food by grinding (processing) grain. Then human civilizations move from hunter gather to more agrarian lifestyles producing more sophisticated means of larger food production and distribution, and ultimately our more modern lifestyle of large-scale mass food production and processing.

We now live in a world of nutritional excess but our body’s still use metabolic pathways that were evolutionarily selected for survival in a world of food scarcity. This would be alright if our energy exertion was balanced with our glucose/fructose intake but our sedentary lifestyles and our proclivity for more processed and sugar enriched foods keep us in a state of metabolic imbalance.

Metabolic imbalances drive a disease pathway that starts with excess insulin levels, then insulin resistance in the end organs, then increased visceral fat accumulation, non-alcoholic fatty liver disease, elevated lipids and finally type 2 diabetes. All along this path we see acceleration to many other chronic diseases, especially the main ones that kill the vast majority of us as we age: heart disease, cerebral vascular disease, neurodegenerative disease and cancers. Maintaining metabolic balance can potentially slow or delay those chronic diseases 5, 10 or even 20 years. We can track one’s state of balance/imbalance through laboratory tests however these can be variable based on genetics and epigenetic factors such as: diet, exercise, medications, underlying disease, stress and sleep. In the big picture, if there is one, albeit complicated, variable we can manipulate to improve our health span it would be to maintain metabolic balance.

Schedule to explore where you stand regarding metabolic balance and what strategy best suites you to improve it.