Juvenon Health Journal volume 10 number 4 april 2011
By Benjamin V. Treadwell, Ph.D.
Perhaps you’ve heard the saying, “Life is short; eat dessert first.” For some, it’s more of a mantra than a joke. In fact, sugary foods can literally become addictive. The reasons are complex and the subject of ongoing neurobiological research. But the results of consuming too much sugar — upsetting our metabolic balance and, consequentially, our health — can be explained biochemically.
How can something as tasty as sugar be bad for us? The simple answer is, as a species, we are not physiologically adapted to consume so much sugar. Our predecessors were virtually never confronted with excessive amounts of sucrose, fructose and refined grain products. Consequently, humankind’s biochemical pathways evolved to most effectively process foods, and their nutrient constituents, which provided maximum energy and optimum health.
Today, foods are relatively easy to obtain at reasonable prices. Some of the most economical choices, however, offer the lowest nutrient content as well as an exorbitant amount of simple sugars. At 99 cents, a half-gallon of soda, for example, may seem like a bargain until you consider the high cost to your health.
Is sugar really that toxic? Let’s consider how a body-shocking dose of sugar (the amount in soda) affects the organs of the body.
Beta Cell Burnout
The human body’s very first response, when confronted with a high dose of sugar in the blood stream, involves the sugar-responder organ, the pancreas. The sugar activates cellular genes in a specific set of the organ’s cells, beta cells, to produce the pancreatic hormone, insulin. The greater the blood-glucose, the harder the beta cell has to work to synthesize and secrete enough insulin to move the glucose from the blood into other cells for energy.
Already, the body is facing the first, potential sugar-caused problem. Beta cells, if confronted with large amounts of sugar on a regular basis, have a difficult time maintaining an energy supply sufficient to feed the cellular machinery involved in synthesizing the insulin peptide. Over time, a high-sugar diet can cause beta cell burnout, so to speak, rendering the cells unable to respond to circulating glucose.
Eventually, the pancreas wears out, essentially becoming inactive with a sharp decline in its ability to produce insulin. Even while this is happening, however, the list of negative biochemical effects from excess sugar is getting longer.
Attack of the Inflammatory Cells
For a period of time, the high blood glucose is removed from the circulation by a corresponding glucose-induced increase in circulating insulin. The insulin does its job, binding to cognate receptors on fat, muscle and liver cells, essentially opening doors to allow the glucose to enter.
But, when large amounts of glucose enter a cell in a short period of time (the case with a high-sugar diet), they activate the machinery in the cell (acetyl CoA carboxylase, mTOR) designed to convert glucose to storable fat. This rapid cellular process actually starts with the excess sugar being converted into a fatty acid (a building block of fat) known as palmitic acid.
Recent research (See this issue’s “Research Update.”) has also implicated palmitic acid in the activation of inflammatory metabolic pathways and their by-products (TNF alpha, IL-6, NF-kB, IL-1, caspases). Intended to target viruses, bacteria, toxins, etc., this mechanism seems to confuse palmitic acid with a pathogen.
(Aside: Why is this mechanism built into our bodies? According to one theory, it’s part of an ancient immune system, activated by humankind’s high-sugar diet, which is relatively new in the evolutionary scheme of things.)
Unfortunately, the cellular mechanisms in place to respond to glucose (cellular machinery and insulin-sensitive biochemical pathways) are innocent bystanders that get caught in the crossfire, with some associated “collateral damage.” The product of this intense battle is a cell with damaged machinery that can no longer respond to insulin/glucose to let glucose into the cell. This condition is known as insulin resistance, a precursor of type 2 diabetes (T2D).
In addition to setting off an inflammatory reaction, the palmitic acid is converted to fat, resulting in bloated fat cells and a fatty liver. The excess fat eventually enters muscle and other tissues, clogging the cellular machinery and coming full circle to the insulin-producing organ, the pancreas. In fact, studies indicate an excess of palmitic acid, in plasma and tissues, may be an early indicator of metabolic syndrome, which can also potentially lead to T2D.
The story doesn’t end with type 2 diabetes. It seems numerous age-related health concerns — cardiovascular conditions, atherosclerosis and Alzheimer’s to name a few — may be linked to sugar-associated inflammation and excess fat.
The U.S. Department of Agriculture is even taking note of newer findings on diet and limiting sugar intake. The four food groups guide, popular in the 1970s, was replaced by the “Healthy-eating Food Guide Pyramid in 1994,” which was updated as “My Pyramid” in 2005 and supplemented with the “Dietary Guidelines for Americans” in 2010. The “Dietary Guidelines” describe a healthy diet, in part, as one that is low in “added sugars.”
A high-fat diet can have similar effects to high sugar consumption but, after decades of warnings from our medical professionals, we’re more likely to avoid fatty foods. As it turns out, because high sugar intake is so rapidly converted to fat, it may be even more damaging.
Fighting the Fat and Inflammation
Other than never eating sugar again (no dessert first or otherwise), is there anything we can do to attenuate the damage?
Recent human cell culture and live animal studies have yielded promising preliminary results. Supplementing with certain nutrients, including resveratrol, alpha lipoic acid, N-acetyl cysteine (NAC) and naringin, seems to inhibit the biochemical pathways active not only in fat synthesis, but also in inflammation.
Additional research is definitely indicated. However, in previous studies, side effects for these nutrients have been minimal. So, the best course of action may be a combination of limiting simple sugars in your diet, exercise, generally good nutrition and, on those occasions when your willpower loses and the double-fudge brownie wins, taking one or more of these supplements, after consulting with your health professional.
Dr. Treadwell answers your questions.
question: Although moderation is, obviously, the best approach, if an event or occasion may lead to serious partying (drinking), is there a compound or nutrient I might take to minimize the deleterious effects of alcohol? And could this “remedy” cause intestinal complications? Thank you. —A
answer: The Juvenon product I suggest taking, before and after too many cocktails, is Q-Veratrol. Take two capsules a couple hours before the party and another two the following morning.
Although Q-Veratrol was developed primarily for heart health, supporting the high-energy requirements of heart cell mitochondria, its combination of antioxidants can also help protect against the effects of alcohol-induced oxidants. One component, N-acetyl cysteine (NAC), could be particularly beneficial.
In addition to the vascular benefits of helping to lower homocysteine levels in the blood, NAC also seems to support immune response. Perhaps most pertinent to your question, it’s also involved in making the endogenous antioxidant glutathione (GSH), one of the most important antioxidants for all the body’s tissues.
Q-Veratrol is generally well tolerated, with no digestive system side effects. That said, it might be best to take the compound with food as a preventive measure. It’s always a good idea to consult with your own health professional, too, before taking any dietary supplement.
Dr. Benjamin V. Treadwell is a former Harvard Medical School professor.
A research team, from the University of North Carolina at Chapel Hill, undertook a study to examine the association between inflammation, a high-fat diet (HFD) and type 2 diabetes (T2D). They published their methodology and results in the article, “Fatty acid–induced NLRP3-ASC inflammasome activation interferes with insulin signaling,” in a recent issue of the journal Nature Immunology.
The investigators were aware of previous work demonstrating the inflammatory effects of high levels of fatty acids (HFD), specifically the saturated fatty acid palmitate. The early studies showed a saturated fatty acid-induced activation of the primitive immune system contained on the surface of blood cells, the macrophages.
This immune system consists of specific receptors, TLRs (Toll Like Receptors), which are designed to recognize and bind foreign substances, such as bacteria and viruses. Once the pathogen is bound to the receptors on the macrophage, a trigger is pulled to activate genes responsible for production of inflammatory substances, (cytokines, TNFalpha, IL-1, IL-6, VCAM etc.). While this cellular response helps destroy the pathogen, as originally designed, it also creates havoc for the surrounding tissue, collateral damage. If significant, the collateral damage can lead to disease.
For the current study, the researchers’ goal was to determine if another primitive immune system, the inflammasome cellular machine, is also activated by elevated levels of saturated fat. Additionally, their work was designed to determine how the fat induced the activation, and whether/how it interfered with insulin signaling, possibly culminating in T2D.
In vitro experiments revealed a complicated metabolic pathway involving numerous cellular signaling molecules, all required for the activation of the genes of inflammation in the macrophage. One key molecule involved in a full-blown inflammatory response was the saturated fatty acid palmitate.
This palmitate-dependent inflammation triggered production of the inflammatory cytokines, IL-1 beta and TNF alpha. These two factors initiated a cascade of events, ultimately preventing normal insulin signaling in insulin target tissues (fat cells, liver cells and muscle cells, as well as pancreatic cells) and resulting in insulin resistance.
In vivo experiments, with an HFD-induced mouse model, seem to confirm the connection between inflammasome-promoted inflammatory cytokine production, reduced insulin signaling and insulin resistance.
Both the in vitro and in vivo experiments implicate the saturated fat, palmitic acid, as a causative agent in insulin resistance, potentially leading to T2D. The findings seem to suggest an explanation for sugar’s association with this health concern, too, since excessive amounts are metabolized to palmitic acid. (See “Sugar: should it have a warning label?”, in this issue, for more on the effects of excess sugar consumption.)
Read 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.