I have written about calorie restriction (CR) a number of times in this blog. CR is the most-proven approach to life extension, involving an ancient biological pathway that works across a variety of species. This blog entry focuses on CR mimetics, substances that can presumably produce the same results as CR, and focuses particularly on mannoheptulose, a sugar in avocados that seems to do the trick.
Ample background on CR can be found in my blog entries Calorie Restriction, longevity, and waiting for proof of what works, Calorie restriction research roundup – Part I, and Calorie restriction research roundup – Part II. These entries discuss the molecular pathways involved in CR, and the Part II entry touches on the possible use of resveratrol as a CR mimetic. These three blog entries ref, ref, and ref touch on the SIRT1 longevity gene and how it activates the CR pathway and on resveratrol and other drugs being developed as likely CR mimetics. However the blog entry What does Resveratrol do? cites research that throws into question whether resveratrol really activates SIRT1 and is in fact a CR mimetic.
Actually, a number of substances have been proposed as CR mimetics including several in the anti-aging firewalls combined supplement regimen: resveratrol, carnosine, alpha-lipoic acid, acetyl-l-carnitine, and mixed antioxidants(ref). The proposed list also includes metformin, gymnema, 2-deoxyglucose, aminoguanidine, hydroxycitrate, thiazolidinediones, lodoacetate, modulators of NPY, exandin, PYY3-36, leptin, oxaloacetate, cinnamon and avocado extract. I focus here on avocado extract because there seems to be some solid research relating to it.
A 2009 publication from researchers at several collaborating institutions tells the story, Mannoheptulose: glycolytic inhibitor and novel caloric restriction mimetic. “Caloric restriction (CR) is the most robust and reproducible strategy for retarding aging. Benefits of CR have been demonstrated in multiple species, but application to human or companion animal aging represents a challenge. In 1998 the concept of CR “mimetic” (CRM) was introduced as a method to obtain “anti-aging” and health-promoting benefits of CR without reducing food intake. We hypothesized that an effective CRM would best mimic the effects of CR if it impeded initial stages of energy metabolism. We focused initially on glycolytic inhibition using 2-deoxyglucose (2DG). Upon entry into cells, this glucose analog is phosphorylated and becomes a strong competitive inhibitor of phosphohexose isomerase. 2DG effectively induces a CR-like state in rats based on metabolic effects such as reduced plasma glucose, insulin, body temperature, pulse, heart rate and inhibiting tumor growth. Results show 2DG has a narrow window between efficacy and toxicity so recently we shifted our focus to mannoheptulose (MH), a seven-carbon sugar that reduces glycolysis via hexokinase inhibition. MH appears non-toxic with negligible effects on food intake and BW, and increased insulin tolerance by 25% in mice. MH extends median and maximal lifespan (~15%) in D. melanogaster and median lifespan (~30%) in C3H/HeJ mice. These findings, coupled with simple extraction from avocados, suggest that MH may be a practical, highly effective CRM.”
“Mannoheptulose is a hexokinase inhibitor. It is a heptose, a monosaccharide with seven carbon atoms. By blocking the enzyme hexokinase, it prevents glucose phosphorylation. As a result less dextrose units are broken down into smaller molecules in an organism. It is found as D-mannoheptulose in avocado(ref). ” In simple terms, it works to block the metabolism if glucose.
From ScienceNews April 20, 2009 “So Roth and his team (from P&G Pet Care, Wayne State University, Southern Illinois University and the Pennington Biomedical Research Institute) have been mining avocados for an alternative — MH (for mannoheptulose). It’s a fairly simple sugar with a 7-carbon backbone. — When fed to mice in fairly concentrated doses (roughly 300 milligrams per kilogram of an animal’s body weight), it improved insulin sensitivity and the clearance of glucose from the blood. Meaning it helped overcome diabetes-like impairments to blood-sugar control. MH supplementation also improved the ability of insulin, a hormone, to get cells throughout the body to do its bidding (and that’s a good thing). –MH revved up the burning of fats in muscle. That’s the opposite of fat deposition and something that these scientists note “would be an expected effect of a calorie restriction mimetic.” — Treated mice also lived longer — some 30 percent longer than untreated animals. And they were happier, I’m guessing, because they didn’t have to give up most of their chow to achieve this life extension. Indeed, their food intake and weight matched that of untreated mice.”
I remark that the 30% life extension in normal mice from taking mannoheptulose beats the 0% life extension in normal mice achievable from taking resveratrol. Resveratrol appears to extend the lives only of obese mice on a high-calorie diet, extending their lifespans to those of normal mice(ref).
I note that the supplement industry is already out-there marketing avocado extract with write-ups describing weight loss, control of hypoglycemia, promotion of heart-health and other benefits(ref). For example, see this avocado extract “obesity protocol.” It appears that the available supplements include at least one product with standardized mannoheptulose sugar content(ref).
I mention again that I have no affiliation with or economic interest in any providers of foods, medicines or health supplements or products. But I do love avocados and eat them at every opportunity.