Wednesday, April 9, 2014

Will Glucosamine Make Us Live Forever? Probably Not, But in Mice the Low-Carb Mimetic Effects Make 10% Possible - In Humans, This Would be ~9 Years! Too Good to Be TRUE?

One of the lead scientists is so convinced that the 10% life-extension the resear- chers observed in rodents will occur in humans, as well, that he is already taking glucosamine supps everyday!
Next to not eating at all, not eating any carbs has recently become all the rage in the "how do extend the lifespan of stupid worms"-research all over the world. Now, I am all for eating less carbohydrates than the people who came up with "Your Plate", my American friends consider optimal.

Yes! I am even in for skipping carbs altogether, but not for a lifetime (!) which is what would be necessary to reproduce the life-extending effects Schulz et al. observed in their 2007 study on the effects of carbohydrate restriction on the lifespan of the notorious (not B.I.G but) B.I.R. as in "big bad roundworm" (Schulz. 2007).

You can learn more about hormesis & life extension at the SuppVersity

Blocking Inflammation = Choking the Fite

NAC = Reduced Damage & Anabolism

Vitamin E Only Useful W/ Intense Exercise?
Are You Stressed Enough For A Longer Life?

Inflammation is a True Fat Burner

Are Vitamin C + E Really Bad for Healthy People?

Now, about seven years later, my favorite anti-ROS-theory-of-aging researcher Michael Ristow and his colleagues some of whom had been involved in the previously cited experiment as well was able to show that bathing the worms in glucosamine will elicit similar life-extending effects (Weimer. 2014).

With only 5% the overall increase in life-expectancy was yet significantly lower than in the "carb restriction" study from 2007, but - and that's actually way more important - unlike cutting carbs, which had failed to produce any effects in a rodent model, the mice who received the glucosamine as an adjunct to their diet, when they were already 100 weeks of age (in human years that's approximately 65 years) lived almost 10% longer than their peers in a non-glycosamine-enhanced control group.
Just to make that clear: We are talking about around 8 additional years of human lifespan! If the results translate from a small mouse who does not stuff itself with junk food all day to the average fast-food addicted Westerner, who follows Winston Churchill's motto "No sports!"
Even if the life-extension did not work, though, couch potato and aging athlete will would probably both benefit from the pronounced improvements / amelioration of the age-induced defects in glucose control, which were significantly reduced in the rodents on the high glucosamine groups.
Figure 1: The decreased ATP stores that come with the "low carb mimicry" effect are not exactly what someone who wants to hit the weights in his old age, would want (Weimer. 2014)
Unfortunately, theses improvements in glucose metabolism come at cost. Ristow et al. found out, glucosamine feeding promotes the breakdown of amino acids in both worms and mice - a breakdown of which the scientists say that it is characteristic of the "metabolic state of a low-carb diet".

In view of the fact the both groups of mice consumed identical amounts of carbohydrates, it's thus only logical to assume that the provision of adequate amounts of glucosamine inhibits the use of glucose from the diet and will thus yield similar metbolic (side) effects as a real low-carb diet - yet without having to skip on pasta, pizza and (of course ;-) tons of sweet potatoes.
Figure 2: At normal glucose levels (<35%) glucosamine reduces skeletal muscle  GLUT-4 expression and glucose disposal (Baron. 1995),
Should we now all start to take glucosamine supplements? According to the accompanying press release Michael Ristow thinks so and actually he even acts on his believe stating: "This [i.e. that everyone should take glucosamine supplements] may be considered a valid option, and yes, I have started taking glucosamine myself."

Whether that's actually a good idea or not, is in my humble opinion still questionable. Previous studies have after all linked high glucosamine to the development of insulin resistance (Baron. 1995; Rossetti. 1995; Shankar. 1998); and a compromised glucose metabolism would certainly not the best premise for a 10% longer life - right?

On the other hand, recent reviews have refuted the notion that glucosamine supplementation increases the risk of insulin resistance, because the necessary tissue levels to generate negative effects as they are displayed in Figure 2 would never be reached with oral supplement (Anderson. 2005). Moreover, Ristow himself mentions that two recent epidemiological studies on more than 77,000 individuals suggest that intake of glucosamine supplements is associated with reduced mortality in humans (Pocobelli. 2010; Bell. 2012) and says: "Unlike with our longer living mice, such an association is no definite proof of the effectiveness of glucosamine in humans, but the chances are good, and since unlike with most other potentially lifespan-extending drugs there are no known relevant side effects of glucosamine supplementation, I would tend to recommend this supplement" (from press release from the ETH Zurich).
  • Anderson, J. W., R. J. Nicolosi, and J. F. Borzelleca. "Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy." Food and Chemical Toxicology 43.2 (2005): 187-201.
  • Baron, A. D., et al. "Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity." Journal of Clinical Investigation 96.6 (1995): 2792.
  • Bell, Griffith A., et al. "Use of glucosamine and chondroitin in relation to mortality." European journal of epidemiology 27.8 (2012): 593-603.
  • Pocobelli, Gaia, et al. "Total mortality risk in relation to use of less-common dietary supplements." The American journal of clinical nutrition 91.6 (2010): 1791-1800.
  • Rossetti, Luciano, et al. "In vivo glucosamine infusion induces insulin resistance in normoglycemic but not in hyperglycemic conscious rats." Journal of Clinical Investigation 96.1 (1995): 132.
  • Shankar, R. R., J-S. Zhu, and A. D. Baron. "Glucosamine infusion in rats mimics the β-cell dysfunction of non—insulin-dependent diabetes mellitus." Metabolism 47.5 (1998): 573-577.
  • Weimer, Sandra et al. "D-Glucosamine supplementation extends lifespan of nematodes and of ageing mice." Nature Communications (2014), doi: 10.1038/ncomms4563