Juvenon Health Journal volume 10 number 3 march 2011
By Benjamin V. Treadwell, Ph.D.
Life is a balancing act. How often have you heard that from friends, family, teachers, the media? According to many studies, people who can find the happy medium between work and play, time for friends/family and for themselves, are often the most successful and well-adjusted. Let’s extrapolate that concept to maintaining your health (essential to enjoying a balanced life).
You’ve probably been told about the importance of a balanced diet thousands of times, too. In this issue of the Juvenon Health Journal, we’re going to get even more specific, or microscopic if you will. New health research has shown that too much of one particular fat in our bodies may be directly related to certain health concerns. However, these effects can be offset (brought into balance) by a relative increase in the presence of, surprisingly, another fat.
We’ve known for some time there’s a connection between obesity and many health concerns: metabolic syndrome (high blood pressure and blood sugar, unhealthy cholesterol levels, large waistline), type II diabetes, heart disease, liver disease, pancreatic dysfunction and others. The mechanisms involved, however, are just beginning to be understood.
Fat is actually readily synthesized in our cells from most any food (especially the simple sugars common to junk food) consumed in excess. One particular fat, palmitic fatty acid (C-16:0), seems to be receiving the most attention with respect to its negative effects on health.
This saturated fat (16 carbons in length with zero unsaturated bonds) is present in many foods including meats, vegetables and fruits. But what many don’t realize is that ingesting excessive amounts of sugar, which is rapidly converted to palmitic acid in our tissues, constitutes the greatest source. Stored as palmitic acid triglycerides (three palmitic acids strung on a glycerol molecule) in fat cells, this fatty acid has been the subject of research, demonstrating an association between high levels and metabolic syndrome symptoms, in particular insulin resistance.
How can we “balance” unhealthy palmitic acid levels? Decreasing our intake of lean steak won’t do it. On the other hand, limiting consumption of high glycemic foods, like cakes and pastries, is one way to have a significant effect on lowering the rate of synthesis and storage. Could olive oil be the key to another?
Olive Oil Answers
Epidemiological studies have linked populations consuming significant quantities of olive oil with a lower incidence of metabolic syndrome. Previous explanations were largely speculative, but recent research has provided key insights.
Seventy-one percent of the fat contained in olive oil is monounsaturated oleic acid (C18:1). This fatty acid interferes with the palmitate (salt by-product of palmitic acid) induced activation of a gene, dihydroceramide desaturase (DES). DES activation produces a molecule, ceramide, known for its metabolic signaling function.
Ceramide is associated with the pro-inflammatory state and related markers of inflammation, conditions common to metabolic syndrome and subsequent disorders such as type II diabetes. Although the precise mechanism is not known, high levels of ceramide do inhibit key steps involved in the insulin pathway, promoting insulin insensitivity.
This relationship prompted a current study (See this issue’s “Research Update.”), with muscle cells isolated from mice, to determine if the activity of the insulin-regulated pathway could be improved by targeting the DES enzyme to inhibit ceramide synthesis. Not only were the results positive but, because the cells were incubated in the presence of oleate and palmitate versus palmitate alone, they also suggest oleic acid may help attenuate the pathological effects of palmitate on insulin resistance.
Burning Bad Fat
The story of olive oil’s positive health effects continues. More recent work has implicated oleic acid in the activation of a specialized transport molecule in the mitochondrial membrane, referred to as carnitine palmityl transferase 1 (CPT1).
As the name implies, this transporter carries palmitate across the membrane to the inner compartment of the mitochondrion (the cell’s energy dynamo). Here it is metabolized (burned), producing useful cellular energy while reducing levels of the toxic fatty acid and its capacity to trigger DES activation and ceramide synthesis.
More Birthdays, More Ceramide
These findings on olive oil seem promising, but the news about the biological molecule, ceramide, is not so encouraging. Its presence in the membranes of cells (including mitochondrial membranes), already linked to inflammation, has been shown to increase with age.
As previously noted, high levels of ceramide are known to dysregulate the insulin pathway, leading to insulin resistance and, potentially, type II diabetes. Some researchers theorize that other age-associated health concerns are also the consequence of increased oxidative stress, ultimately due to dysregulated metabolic pathways.
A report on ceramide levels in the mitochondrial membranes of aging heart tissue cells (cardiac myocytes) seems to support this hypothesis. Elevated ceramide corresponded to a decrease in levels of a major cellular antioxidant, glutathione, as well as a decline in the health of the cellular organelle itself.
It seems that tissues of older, but not young, animals have a propensity to produce excess amounts of ceramide and other inflammatory molecules. Why the higher levels? In the case of ceramide, it appears that another unfortunate consequence of aging is the dysregulation of the metabolic pathway leading to its synthesis and involving the key enzyme mentioned earlier, DES.
Is it possible to re-adjust the regulators of this pathway to bring it back to a more youthful, balanced state?
More Alpha Lipoic Acid, Less Ceramide
We’ve already touched on oleic acid/olive oil’s capacity to interfere with DES activation and, therefore, ceramide synthesis, as well as its role in transporting palmitate to be metabolized by the mitochondria. Dr. Tory Hagen, from the Linus Pauling Institute, has recently introduced another potential solution.
Remember that one of the consequences of an over-production of ceramide is a depletion of the cellular antioxidant glutathione. (See previous section.) In Dr. Hagen’s experiments, feeding aging rats alpha lipoic acid (ALA) had a profound effect on restoring glutathionine levels to the mitochondria of cardiac myocytes. The restoration of glutathione, in turn, seemed to inhibit ceramide synthesis.
Did lipoic acid supplementation reset the metabolic pathway involved to a more youthful, healthy state? Additional studies are warranted to determine the exact mechanisms involved with animals and whether they apply to humans.
It seems we’ve only begun to touch on the complexities of fats. Recent work has demonstrated the health benefits from polyunsaturated fats, like the omega-3’s present in fish oil. (See Juvenon Health Journal, Volume 9, Number 10, “Fish Oil Fatty Acids: Should They Swim In Your Blood Stream.”)
Investigators are also finding that saturated fats of different lengths have very different properties. For example, stearic acid (C18:0), a saturated fat with two carbons more than palmitic acid, has no effect on stimulating levels of mRNA for DES. Interestingly, recent research involving stearic acid showed that inhibiting an enzyme, steroyl CoA desaturase (SCD), even though it converts stearic acid to oleic acid, actually improves insulin sensitivity.
Overall, it’s becoming obvious that individual fats have very different biological activities/effects.
Let the studies and discoveries begin. (And let’s continue on a related subject in our next issue, with a closer look at the greatest source of palmitic fatty acid, sugar, and its potentially unhealthy impacts.)
Dr. Treadwell answers your questions.
question: I’m writing to see if you can address my concerns regarding the Cal-Mag supplement. I’m considering the (Juvenon’s) Century Club, in which it is included, because this seems to be the best value. However, some time ago, it seems I read something about too much calcium taken by men could lead to hardening of the arteries or some other adverse effect. For this reason, I’ve never taken any calcium other than what is included in a multi-vitamin. Your opinion would be helpful. — G
Due to diet, and because the body no longer stores calcium after age 30-35, the U.S. Surgeon General estimates that half of Americans over 50 will be at risk for fractures and low bone mass by 2020. So, supplementing this mineral seems to be advisable, especially as we get older. The benefits — like increasing bone density, regulating heartbeat, even easing occasional sleeplessness — outweigh the potential negative effects. To date, there is no validated evidence linking taking calcium with atherosclerosis or hardening of the arteries.
It is estimated that 61% of the U.S. population do not meet the magnesium RDA. So, again, supplementing seems prudent. Magnesium not only aids in calcium absorption, but has also been credited with actually promoting healthy arteries and helping to maintain normal blood pressure. This mineral seems to play a key role in cellular energy production, too, as well as for about 400 enzyme-catalyzed reactions in metabolism.
I hope I’ve addressed your concerns, G. It’s a good idea to consult with your own health professional, too, before starting to take Juvenon Cal-Mag, or any dietary supplement for that matter.
Dr. Benjamin V. Treadwell is a former Harvard Medical School professor.
A research team from the Medical University of South Carolina and the Ralph H. Johnson Veteran’s Affairs Medical Center, also in Charlotte, recently published “Differential Regulation of Dihydroceramide Desaturase by Palmitate vs. Monounsaturated Fatty Acids: Implications to Insulin Resistance” inThe Journal of Biological Chemistry. The article discusses the group’s experiments, designed to determine the effects of different fatty acids on the synthesis of a bioactive molecule, ceramide.
The study was motivated by previously published work that confirmed an association between obesity, dyslipidemia and certain conditions related to metabolism, including metabolic syndrome, insulin insensitivity, diabetes and heart disease. The researchers hoped to discover the mechanism involved, i.e., whether some of the bioactive molecules derived from fat metabolism, and elevated in conditions associated with obesity, were causal. Furthermore, they wanted to determine if/why some fats actually seem to have health-protective properties.
Specifically, the team proposed that the bioactive molecule, ceramide (elevated in the obese and the aged), might play a key role. Their theory was based on earlier work that had demonstrated ceramide was directly involved in promoting an increase in the production of inflammatory molecules. These molecules were previously shown to be instrumental in the development of insulin insensitivity.
The investigators used a cell culture system with mouse myoblasts (skeletal muscle precursor cells) to examine the effects of a number of different fatty acids on the production of ceramide. They found the most potent was the saturated fatty acid palmitate (C16: 0).
Additional work isolated the mechanism: palmitate stimulates ceramide synthesis by acting on the gene coding for an enzyme. The gene and its corresponding enzyme are known as DES, or dihydroceramide desaturase. This enzyme acts on the precursor to ceramide, dihydroceramide, to produce the final product.
Interestingly, saturated fats such as stearic acid (18: 0), the most common fat in red meat, did not have any effect on DES. The authors cite this evidence of the individualized properties of different species of saturated fats, recommending against grouping them together as contributing to negative health effects (at least not by acting on the same biochemical pathways).
The most noteworthy observation resulting from this study may be the positive effect of a monounsaturated fat, oleic acid (18: 1). When added to the culture system, oleate inhibited synthesis of DES at the gene level. Apparently, this inhibition virtually neutralized palmitate stimulation of ceramide synthesis. In other words, the ceramide levels in oleate-palmitate treated cultures were the same as for controls incubated without palmitate.
Oleate represents roughly 70% of the fat in olive oil, consumption of which has been linked to a decrease in the incidence of health concerns related to metabolism. The authors conclude by suggesting that olive oil should be considered as a therapeutic for prevention of metabolic syndrome and other conditions associated with dyslipidemia, including insulin resistance.
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.