Juvenon Health Journal volume 2 number 7 july 2003
By Benjamin V. Treadwell, Ph.D.
The incidence of type 2 diabetes throughout the world is estimated to grow to 250 million people within twenty years. In the United States, 30% of newborns are expected to develop the disease during their lifetimes. These statistics are alarming, but they don’t have to be anywhere near that bad.
Development of type 2 diabetes
Epidemiological evidence clearly indicates that lifestyle, diet and exercise have a tremendous effect on the development of Type 2 diabetes. Many of us are properly attentive to our safety, seat belts, air bags and our children’s safety, but far less concerned with the safety of our physical health. Regularly drinking a six-pack of soft drinks and watching the tube with a burger and fries are dangerous but often unrecognized health-risks.
Let’s start with a little background on type 2 diabetes. (Although it is sometimes referred to as adult-onset diabetes, the age of onset is steadily dropping in the United States.)
Let’s look at the association between the accumulation of intracellular fat and diabetes. Insulin resistance is an early warning sign of impending diabetes. The condition is characterized by a gradual impairment in cells’ ability to take up, store and utilize glucose for energy. Within 10-20 years it typically progresses to classical type 2 diabetes. The cells appear to lose their capacity to respond to insulin.
The incidence of insulin resistance increases with age, and by 65 years of age, we have a significant chance of developing this pre-diabetic state. Further investigation of this disorder has discovered a large (40%) increase in fat in muscle and liver cells of seemingly normal older people, as compared to normal individuals 18 to 39 years old.
Increased cellular fat is not just an innocent bystander, but rather a key factor in promoting the disease. Abnormally high levels of cellular fat may activate a series of enzymes (kinases) that in turn alters the molecular structure of key substrates involved in insulin action, affecting the transport and metabolism of glucose. The degree to which key substrates are altered by the enzymes determines the extent of insulin resistance. If the enzymes act extensively on the substrates, the result is a profound inability of glucose to enter cells to be converted to energy or stored as fuel. This is full-blown type 2 diabetes, with characteristically high levels of blood glucose.
OK, cellular fat causes insulin resistance; but what causes the fat to accumulate in muscle and liver cells in the first place?
The answer may involve the mitochondria – the cellular organelles involved in converting fat to energy. Examination of the relative energy production by the mitochondria of two age groups (18-39 years and 65+ years) demonstrated a 40% reduction in the efficiency of the machinery involved in production of energy in the elderly. Interestingly, this level of energy reduction in the elderly is the inverse of the fat content (40% higher) present in the muscle of the older people. In other words, those with more efficient energy-producing mitochondria have less cellular fat.
The investigators in these studies hypothesized that it is inefficient mitochondria, or a decrease in the number of mitochondria, that interferes with the metabolism of fat and results in increased cellular fat deposits, which in turn interfere with insulin action.
This leads to still another question: why do the mitochondria become less efficient as we age?
The mitochondria are susceptible to the action of destructive oxidants produced during cellular metabolism, and more importantly during the production of energy. The DNA of mitochondria is more susceptible to mutations than the cell’s nuclear DNA, because the mitochondrial DNA is more exposed to oxidants and has a much less efficient mechanism to repair oxidant-induced damage. The damage-susceptible molecules in the mitochondria accumulate with age and unfortunately are passed on to mitochondrial offspring (via mitochondrial fission) every couple of weeks (the average life-span of mitochondria).
Finally, what can we do to prevent mitochondrial degeneration and possibly avoid type 2 diabetes?
Unfortunately, a genetic component influences the likelihood of developing diabetes, such as an inherited gene mutation that favors fat accumulation in muscle and liver rather than the fat storage cells, adipocytes. Another sometimes genetic condition associated with diabetes is obesity, a disorder that promotes the accumulation of fat in adipocytes as well as liver and muscle cells.
Even with favorable genetics, there is currently no available magic bullet to insure 100% protection from the events leading to mitochondrial degeneration and diabetes. Nevertheless there are at least three measures we can take to attenuate the degenerative process.
- Diet – Eat a proper nutritious diet, loaded with fruits, vegetables, and sufficient protein. Avoid saturated and hydrogenated fats, and avoid junk food, including the ubiquitous soft drinks loaded with sugar that is converted to fat in the body. Obesity, a common result of poor diet in the U.S., clearly promotes insulin resistance and essentially converts a youngster to an oldster before his/her time.
- Exercise – One of the methods to remove excess glucose and fat from the body is through exercise. An additional benefit from exercise, besides burning excess fuel, is it creates energy demand and promotes the synthesis of mitochondria. This is beneficial, as it helps prevent the build-up of intracellular fat and thus insulin resistance. It also burns fat and increases the number of fat burners (mitochondria).
- Supplement – There is evidence, largely from animal studies, demonstrating that inefficient mitochondria present in aged animals, and characteristic of the pre-diabetic condition, can be invigorated by supplementing their diets with compounds that act on the mitochondria. These compounds, acetyl-L-carnitineand alpha lipoic acid, normally carry out critical functions in the mitochondria, and have been shown to be present at suboptimal levels with age. Evidence indicates that supplementing the diet of an older animal with these compounds maintains mitochondrial function and results in increased energy production and efficiency.
Some researchers believe that lipoic acid increases insulin sensitivity of muscle cells. Evidence from cell culture studies indicates that lipoic acid may increase insulin sensitivity by promoting the differentiation of cells to adipocytes, and thus prevent accumulation in muscle and liver cells, where it can promote the pre-diabetic state. In other words, lipoic acid may help keep the fat out of the muscle and liver cells where it is toxic at high levels.
Alpha lipoic acid has, over the years, attracted considerable scientific and medical attention for its reported properties as a key factor in energy metabolism, a potent antioxidant, an agent to help maintain healthy blood sugar, a promoter of cardiovascular health, and a protector of the nervous system. Researchers have conducted numerous studies under various conditions, and with various forms and concentrations of alpha lipoic acid, to identify and evaluate a wide variety of its attributes and effects. Studies both large and small have involved healthy patients as well as subjects selected in connection with different diseases.
In Germany, results were recently published from a “meta-analysis” of multiple studies assessing the effect of alpha lipoic acid administered intravenously to diabetic patients. This analysis of a potential beneficial drug use of alpha lipoic acid is provided for your information and should not be interpreted as supporting a similar use or benefit of dietary supplements containing alpha lipoic acid. For further information, click 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: I’ve been taking 2 Juvenon per day for four months. I have not experienced any of the effects, physical or psychological, reported by some users. Do you have any data or hypotheses that would explain why some Juvenon users experience dramatic effects, but others do not?
C.F., via email
ANSWER: Your experience is not unusual. A number of people, including Bruce Ames, the founding scientist of Juvenon, do not notice a significant effect from the Juvenon formula.
The function of the compounds in the Juvenon formula is to maintain the energy-producing organelles of the cell, the mitochondria, at a healthy, active state. The likelihood of developing a pathology, such as diabetes or many of the age-associated degenerative diseases, such as Alzheimer’s disease, Parkinson’s disease and others, is decreased with healthy mitochondria.
Even though some people, such as yourself and Bruce, do not experience a noticeable effect, you probably are benefiting from the compounds in the tablet, as they have been demonstrated, in animal studies, to maintain mitochondrial health in old animals. The young animals, on the other hand, had only minimal positive effects from the compounds.
A number of scientific factors may account for the different responses to the formula. While the placebo effect cannot be discounted, more likely explanations include variations in genetics, metabolism, physical condition, diet and age.
It is far better to be on the safe side and maintain mitochondrial health. In this sense the Juvenon formula seems to some people like a vitamin. They know it’s good for them even if they don’t feel an effect.
You might want to test taking a third tablet during the day to see if you feel an effect. I do that on occasion and find a significant boost in energy, especially mental alertness.
Benjamin V. Treadwell, Ph.D., is a former Harvard Medical School associate professor.