Metabolism, Stem cells and Cancer

Diet is one of several lifestyle factors that influences health and disease, such as cancer development. All cells in your body need energy to survive. They get this energy from the food we consume. Therefore, the food we eat have a major effect in all types of processes in our bodies. For example, it will be involved in regulating growth factor and hormone levels, which in turn can regulate tissue homeostasis and tumour initiation.

What type of metabolic pathways do we have? Simplified you can categories metabolism into catabolism and anabolism. Catabolism refers to the process that breaks down complex molecules into smaller molecules and release energy. In contrast anabolism refers to the process which builds molecules the body requires and it usually needs energy for completion. The main different metabolic pathways in humans are; glycolysis, citric acid cycle, oxidative phosphorylation, pentose phosphate pathway, fatty acid metabolism and gluconeogenesis. All these pathways use different sources of nutrients or metabolic intermediates to create energy.

Stem cells are undifferentiated cells that are capable to form all cells in your body, indefinitely. Stem cells have a unique ability to self-renew. This is when stem cells divide to make more stem cells to maintain the stem cell population. Haematopoietic stem cells (stem cells that give rise to all cell types in your blood) include different subsets of stem cells, cells that take care of everyday needs and cells that only ”wakes up” when you have an acute situation, such as blood loss or a disease that require generation of new blood cells. The balance between stem cell self-renewal and differentiation (commitment to a cell type) is a key determinant of tissue homeostasis. If you have a balance in self-renewal and differentiation your stem cells will be able to remodel tissues in response to turnover, damage, and disease.

How do stem cells get their energy? The metabolism of a cell was once thought to be a consequence of the state of a cell however it is now known that cell metabolism plays a crucial role in determine whether a cell proliferates, differentiates or remains resting. Stem cells are believed to balance between glycolysis and oxidative phosphorylation during the maturation to adult stem cells. Glycolysis is where the cell utilises glucose for energy and oxidative phosphorylation is the metabolic pathway that involves oxidation of nutrients to release energy. Even though oxidative phosphorylation is an efficient way of generating energy, it generates an oxidative stress which can further lead to production of free radicals. This process can eventually damage cells and contribute to disease. It it believed that stem cells do not solely rely on oxidative phosphorylation due to the fact that these cells must remain healthy during your whole lifespan, they want to avoid to much “stress” that can cause cell damage. However recent results have shown that fatty acid metabolism which eventually feeds in to oxidative phosphorylation is important for the specific subset of resting long-term stem cells that only “wakes up” during acute situations. However, this is under a lot of investigations at the moment. I believe this research will be very interesting to follow.

What goes wrong during cancer development? Interestingly, many key oncogenic signaling pathways (causing development of tomours) involves metabolic pathways suggesting that metabolic changes are involved in driving the malignant transformation. Cancer cells have a huge need of energy since they are rapidly dividing cells. Cancer cells are mostly surrounded by a stressful environment where concentrations of nutrients and oxygen can vary, sometimes low in energy as well as oxygen. The most studied metabolic state of cancer cells is “The Warburg effect” which is the generation of energy through glycolysis even in the presence of oxygen. It is more rapid compare to oxidative phosphorylation however it doesn’t generate as much energy. Therefore, cancer cells have an abnormal rate of glucose uptake to meet its energy needs. A positron emission tomography (PET) scan uses this abnormal rate of glycolysis by cancer cells to identify the site of the cancer. You get injected with glucose (sugar) combined with a very small amount of radioactive material to see where cells with high glycolysis rate are present. These cells are most probably the cancer cells.

Due to the fact that cancer cells are known to use the Warburg effect, many people suffering with cancer are experimenting with the Ketogenic diet where you consume high fat, moderate protein and low carbohydrate. This will push your metabolism towards fatty acid metabolism instead of e.g. glycolysis. The liver will convert fat into fatty acids and ketone bodies. Cancer cells often lack the ability to use fatty acids or ketone bodies as an energy source and could even be harmed by them, therefore it is sometimes believed that a ketogenic diet could benefit cancer patients. In an ideal world it would be very nice if we would be able to nourish our normal stem cells but starve cancer cells.

What conclusions can we make from this? That we are what we eat. Your stem cells are the most important cells in your body and they need to be nourished well. Metabolism most likely have a strong impact on how your stem cells can shift towards generating different cell types as well as to remain long-term stem cells that are able to self-renew. Whether we can modulate both normal and cancer stem cells with different types of specific diets needs further investigations. However, the main advises you´ll get today in terms of improving your stem cell population is most often the same advice you get for improving general health;

  • Eat clean nutrient dense food
  • Reduce sugar consumption
  • Restrict your calories
  • Lower your triglycerides (your body´s fat storage)
  • Stay active
  • Spend time outdoors

Makes sense right! The food you eat is the food your cells will eat. If you want to improve your chances of having healthy cells for a long time you need to feed them well.

Xx, Sara

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