Mitochondria are the powerhouses of cells. They generate energy from the fats, carbohydrates, and proteins that we eat. The Organix test evaluates how well our mitochondria make energy from foods. When your patient presents with fatigue, weight loss resistance, overweight, or metabolic syndrome, this information can be very useful in designing an effective therapy.
The most efficient way to make energy (ATP) from fatty acids is by B-oxidation in the mitochondria. Carnitine and B2 are needed to shuttle these fatty acids across the mitochondrial membrane. If your patient is deficient in either of these nutrients, the fats can’t cross into the mitochondria and are metabolized in a less efficient manner in peroxisomes. The end products of this reaction are adipate, suberate, and ethylmalonate. So, when these compounds are high in the urine, it tells us that fats are not getting into the mitochondria, thus leading to a decrease in energy production and trouble with “burning” fats. Carnitine receives a lot of press in popular media as being a weight-loss supplement for this reason. Once carnitine levels are restored, fats are “burned” and people can lose weight and enjoy improved energy levels.
Many of you may remember memorizing the steps of glycolysis back in college biochemistry. Glycolysis is the pathyway that takes sugar (glucose) and converts it to pyruvate so that it can enter the citric acid cycle and finally produce ATP in the electron transport chain—a process called cellular respiration. Each molecule of glucose, by the end of cellular respiration, can yield up to 36 ATP.
High levels of pyruvate in the urine can indicate a functional block in this cellular respiration process. To enter the citric acid cycle, pyruvate needs to be metabolized by a large enzyme complex, pyruvate dehydrogenase, a process that requires vitamins B1, B2, B3, B5, and lipoic acid. High levels of pyruvate in the urine can imply deficiencies of one or more of these vitamins.
Under anaerobic conditions, lactate, not pyruvate, is the primary end product of glycolysis. When lactate is high, metabolic acidosis can ensue due to hypoxia, metabolic syndrome, alcohol intake, and many pharmaceutical drugs. Addressing the underlying causes as mentioned above as well as supporting with nutrients such as coenzyme Q10, lipoic acid, and thiamine (B1) is helpful to lower lactate in urine.
The ketone body B-hydroxybutyrate is made from fatty acids when there isn’t enough sugar to use for energy. The term “ketone body” became popular with the introduction of the Atkins diet, which is low in carbohydrates and high in protein and fat. The body prefers to burn carbohydrates as its first source fuel, but when they are exhausted the body uses fat. Ketones are a by-product of this process. Your patient may show high b-hydroxybutyrate if he is on a low-carbohydrate diet, or if he has been fasting for longer than 12 hours. If neither is the case, then you have a great marker for monitoring insulin resistance, and metabolic syndrome. If sugars cannot get into the cell to be used for energy, the body begins making ketones from fatty acids. Interventions include improving insulin sensitivity by a low-glycemic-index diet, exercise, fish oil, and chromium.
Citric Acid Cycle (CAC)
Dietary fat, carbohydrates, and protein are metabolized to a common metabolic intermediate, acetyl-CoA. Acetyl CoA flows directly into the citric acid cycle. Proper functioning of this cycle generates enough NADH to help create ATP in the final stage of energy production, the electron transport chain (ETC). Abnormal spilling of CAC intermediates in the urine can indicate mitochondrial inefficiencies in energy production. Many cofactors are involved in the conversions of these intermediates, including the minerals iron, magnesium, manganese, and the B-vitamins. The ETC is heavily dependent on CoQ10 for its function. If there is a deficiency in CoQ10, CAC intermediates can elevate in the urine. Severity of the CoQ10 deficiency can be correlated with the amount and number of CAC intermediates found in the urine. This information becomes useful when determining whether or not your patient needs only 30 mg of CoQ10, or 300 mg.
If CoQ10 status is normal, extreme high levels like those shown above can be a sign of a greater problem such as heavy metals attacking the ETC. An elevated level of 8-OH-d-guanosine (to be discussed in further detail in a future blog) is a supporting marker for such a hypothesis.
Low urinary concentrations of the CAC intermediates can be a sign of amino acid deficiency, as amino acids are a main filling agent to the cycle. When the CAC intermediates are low, consider supplementation with a free-form amino acid powder to improve energy production. Even better, consider a more targeted approach by testing your patient for fasting plasma amino acid levels to determine a customized compounded blend of free-form amino acids.
In conclusion, urinary organic acid analysis is a great way to get a snapshot of your patient’s mitochondrial function as it relates to energy production and utilization of the foods they eat. Correcting imbalances can make huge differences in your patient’s energy level and ability to lose weight.
Next week we'll take a look at Step 2: B-Vitamin Status. Feel free to comment below as always!