L-carnitine: Re-opening Fat-clogged Mitochondria

Juvenon Health Journal volume 8 number 7 July 2009
By Benjamin V. Treadwell, Ph.D.

Revolution vs. Evolution
The foods just listed have only been available since the agricultural revolution, 100 to 200 years ago. The “revolutionary” increases in wheat production prompted processing into refined flour, which removed much of the wheat’s fiber, vitamins and minerals.

Many of today’s “junk” foods are made from this low-nutrient flour, with added sugar and fat to make them even tastier. This recipe provides the cells of the body with a tremendous amount of energy and, therein, lies the problem.

“How do energy-fish, nutrient-poor foods wreak havoc on our bodies?”

The body is not equipped for excess nutrition, especially in high fat-low fiber and high sugar forms. Man did not develop a metabolic system to manage this kind of excess. In fact, throughout virtually all his evolving existence, it was a constant struggle to just obtain enough food to survive.

Cellular Confusion
Food consumed in excess is invariably converted to fat. Under normal metabolic conditions, fat is transported into the mitochondria, where the bulk of all cellular energy is produced, to be converted to a chemical form of energy (ATP).

Under conditions of excess nutrition (high fat-high sugar diet), the body not only has to contend with transporting and burning fat, but also with removing sugar (glucose) from the blood stream for conversion to energy in the cell’s mitochondria.

“Man did not develop a metabolic system to manage excess nutrition.”

Cells, especially muscle and liver cells, become confused, to the point where they begin to accumulate large stores of partially burned fat molecules. The fat interferes with the cell’s ability to remove glucose from the blood stream. Known as the metabolic syndrome, this condition precedes full-blown diabetes.

L-carnitine Ins and Outs
Recent research has produced more enlightening information on the potential mechanism by which excess fat interferes with metabolism. Working with a mouse model, the researchers showed that mice, fed a high-fat diet, develop metabolic syndrome just as humans do. (They also observed an increased propensity in aged animals, as compared to their younger counterparts.) Examining the mitochondria of the “fat” mice revealed substantial amounts of partially metabolized fat molecules in the energy-producing chambers of their mitochondria.

“How does excess fat interfere with metabolism?”

The investigators also noted unusually low levels (as compared to normal mice) of L-carnitine. It is a well-established biochemical fact that this nutrient acts as a transporter molecule, carrying fat into the mitochondria for energy conversion. What many students of biochemistry may not know is that the cell also uses L-carnitine to carry fat out again. The research team hypothesized that an L-carnitine deficiency was, at least partially, responsible for the pre-diabetic condition.

Adding L-carnitine
Setting out to test their theory, the team fed one group of mice a high-fat diet supplemented with L-carnitine and a second group (the control animals) the same diet, but with no supplement. After two months, the animals on the L-carnitine supplemented diet had normal levels of L-carnitine in their tissues. In addition, their blood glucose levels were much improved, compared to the controls.

Furthermore, mitochondria from the control animals were clogged with incompletely oxidized fat molecules. By comparison, cells from the mice on the L-carnitine supplemented diet contained mitochondria with a healthy ratio of incompletely:completely oxidized fat.

Why the difference? The investigators speculated (and supported with experimental evidence) that the animals on the high-fat, non-supplemented diet developed a deficiency in free or available L-carnitine. Because so much was tied up with transporting the fat into the mitochondria, very little non-fat-bound L-carnitine remained to transport partially oxidized fat molecules out.

Subtracting Glucose
So, that seems to explain the healthier ratio of incompletely:completely oxidized fat in the L-carnitine supplemented mice. But what about the improvement in blood glucose levels?

“Is an L-carnitine deficiency partially responsible for the pre-diabetic condition?”

The researchers theorized that, in the non-supplemented mice, the partially oxidized fat clogging their mitochondria consequently upsets normal metabolism and impairs uptake of glucose. Sufficient L-carnitine, on the other hand, not only removes excess fat from the mitochondria, but also frees-up an important co-factor (Coenzyme A) necessary for glucose utilization. The increase in glucose utilization for energy production stimulates its removal from the blood.

Supporting Metabolic Balance
How similar is man to mouse? Our bodies’ cells also manufacture the vitamin-like substance, L-carnitine, but also at insufficient quantities as we age, especially as we age on an unhealthy high-fat diet. Human studies have demonstrated the health-promoting effects of supplemental L-carnitine as well. Although this research, along with the mouse model cited here, indicates exciting possibilities for L-carnitine as a therapeutic for healthier aging, more human studies are needed to fully demonstrate its potential to support a balanced metabolism.

The Journal of Biological Chemistry recently published “Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control.” Submitted by a team of researchers from Duke University (Durham, NC), East Carolina University (Greenville, NC) and the University of Barcelona (Barcelona, Spain), the article presents the results of an animal investigation into the potential therapeutic benefits of oral administration of the nutrient L-carnitine.

This nutrient functions as a transport molecule for the transfer of fatty acids into the mitochondria. These fatty acids can be converted into metabolites, which are used, along with blood glucose, in the production of energy.

The researchers stipulated that certain conditions, i.e., high-fat diets and excessive consumption of fats and sugars, cause a depletion of L-carnitine in tissues of the body. This deficiency results in the build-up of incompletely oxidized fatty acids in the mitochondria, a metabolic dysfunction that, in turn, inhibits glucose uptake by the cells. The associated increase in blood glucose levels translates to a higher incidence of the pre-diabetic state known as metabolic syndrome.

In a two-month experiment designed to demonstrate the effects of supplementing L-carnitine, the team added the nutrient to a high-fat diet fed to one group of mice. A second group of mice, the control animals, received the same diet without the L-carnitine. The mice treated with L-carnitine showed a significant decrease in blood glucose and an increase in glucose tolerance.

Based on these impressive results, the investigators concluded that supplementing L-carnitine replenishes the nutrient’s cellular pool. Maintaining enough L-carnitine to carry fats out of (reverse fat transport), as well as into, the mitochondria relieves the metabolic stress placed on this cellular organelle.

The outcome is a return to metabolic balance, which includes the import of glucose into the mitochondria and its removal from the blood stream. While more research needs to be conducted, including human trials, the use of L-carnitine may play a future role in helping decrease the risk of developing metabolic syndrome, a precursor for full-blown diabetes.

Read article abstract here.

This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.

Dr.Treadwell answers your questions about Juvenon™ Cellular Health Supplement.

question: Ben, do you think I would have more energy and less need for midday rest periods (I’ve been taking two or three naps a day.) if I increase my daily dose of Juvenon from two pills to three? – J 

answer: Very possibly. Some people have reported an increase in energy after taking an additional Juvenon tablet per day. But make sure the last tablet of the day is taken at least six to eight hours before bedtime. And please let me know if you see a difference.