What’s good for your joints may also be good for a …

Late Life Boost in Longevity
Glucosamine may offer a new bargain for extended life

By Will Block

G lucosamine has long been touted for its ability to promote the replication of cartilage—making for healthier joints—and as a vanquisher of arthritis.* Glucosamine is also known to delay cancer growth.1 What’s more, freely available glucosamine acts as an inhibitor of glycolysis. Glycolysis is the cellular degradation of glucose. This process yields ATP as an energy source, which lowers blood glucose levels, mimicking a low carbohydrate diet, and increasing health and longevity, according to a new scientific report.


* See “Postmenopausal Women Benefit from Glucosamine” in the September, 2004 issue; “Supplements Put the Brakes on Osteoarthritis” in the December, 2003 issue; and “Glucosamine Sulfate Scores, Again, Against Arthritis” in the March, 2003 issue.


The Equivalent of a Human Living Eight Years Longer

In this new study, seasoned researchers—predominantly interested in life extension interventions—suggest that glucosamine may actually have another use that could have potential implications in extending human life span.2 The title clearly states that, “D-Glucosamine supplementation extends life span of nematodes and of ageing mice.” Published in Nature Communications on April 8, 2014, Swiss and German researchers experimented with two groups of mice whose age was 100 weeks—which is old for mice. The mice in the first group were given glucosamine as a supplement to their normal diet, while those in the second group did not receive glucosamine (the controls). The results indicate that glucosamine in relatively moderate doses (about 4 g/day for a human) could extend longevity by 10% when taken late in life (at the human equivalent age of 65 years). That’s an expansion in longevity that translates to eight years of extra life for humans! So if your “normal” death age would have been 84, with glucosamine (if it works for humans) you would live to 92. That’s a big deal!


† No such calculations were provided in the paper. However, Durk Pearson & Sandy Shaw computed the human equivalence from the data provided and their knowledge of mice chow, into which the glucosamine was blended.


Protection from Diabetes Also Found

The researchers also observed that the glucosamine-fed mice did not just live 10% longer than the controls; they also had improved glucose metabolism, which indicated that they were protected from diabetes, a chronic disease that commonly affects obese individuals and the elderly. That could certainly play a role in longevity.

Glucosamine Produces the Effects of a Low-Carb Diet

The Swiss/German scientists also studied the effects of glucosamine on nematode roundworms (Caenorhabditis elegans) and in particular their mitochondria, the parts of the cell responsible for energy conversion. They observed that glucosamine increased the breakdown of amino acids and fatty acids, similar to the effects of consuming a low-carbo­hydrate diet. Low-carbohydrate diets are known to reduce blood pressure and harmful blood fats. These effects were independent of the hexosamine pathway through which glucosamine’s cartilage/joint/arthritis properties are thought to operate. Glucosamine was found to extend life span in C. elegans by impairing glucose metabolism that activates AMP-activated protein kinase (an enzyme that plays a role in cellular energy homeostasis) and increases mitochondrial biogenesis (the increased creation of mitochondria in our cells). The longevity of the roundworms was extended by 5% in the study.

Used for Many Years with Low Side Effects

The researchers noted that the effects of glucosamine on mice and worms do not provide proof that glucosamine can extend human life. However, study researcher author Michael Ristow, M.D. from the Energy Metabolism Laboratory at the Swiss Federal Institute of Technology Zurich in Switzerland said that unlike other substances that could potentially extend life span, glucosamine as a supplement has been in use for many decades and is not associated with relevant side effects other than rare allergic reactions.

Presumed Role of Reactive Oxygen Species

Dr. Ristow is a German medical researcher who has published influential articles on biochemical aspects of mitochondrial metabolism, and particularly about the health-promoting role of reactive oxygen species (ROS) in diseases like type 2 diabetes, obesity and cancer, as well as general aging due to a process called mitohormesis. Hormesis is the term for generally favorable biological responses to low exposures to toxins and other stressors. A pollutant or toxin or ROS showing hormesis thus has the opposite effect in larger, rather than smaller, amounts. Mitohormesis is hormesis in mitochondria.


Glucosamine may actually
have another use that might
extend human life span.


Cited Favorably for His Research

Of interest, Dr. Ristow has been cited before in Life Enhancement for his paper, “Low-dose lithium uptake promotes longevity in humans and metazoans,”3 about which we commented favorably in an article titled “Lithium Promotes Longevity, Mood, and Love” in the the January 2013 issue. We also cited his paper, “Neurodegenerative disorders associated with diabetes mellitus,” about which we wrote, “Avoiding Diabetes Can Help You Avoid Alzheimer’s” in the August, 2004 issue.

Durk Pearson & Sandy Shaw have also found reason to cite Dr. Ristow. In their Volume 17 No. 2 • February 2014 issue of Life Extension News, they wrote about his article, “Antioxidants prevent health-promoting effects of physical exercise in humans.”4 “The scientists [Ristow et al] interpreted the results to be a consequence of hormesis—that is, these beneficial effects of exercise were the result of adaptive changes induced by ROS, which were prevented when adequate amounts of antioxidants were present. ‘Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity. Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans.’” [References removed. Emphasis added.]


Supplementation with antioxidants
may preclude these health-promoting
effects of exercise in humans.


This is important because in the Swiss/German paper, the authors seem to believe that antioxidants interfere with glucosamine life span extension, at least in C. elegans. They wrote, “Mitochondrial ROS signaling in nematodes and, in particular, mitohormesis suggests that a low-dose, transient increase in ROS formation promotes metabolic health and life span, thereby questioning the free radical theory of ageing. To test whether the increase in ROS is essential for a GlcN [glucosamine]-mediated extension of life span, we repeated the initial life span experiment in the presence of the antioxidants butylated hydroxy anisole (BHA) and N-acetyl-cystein (NAC), respectively. Although neither BHA nor NAC had a detectable effect on C. elegans life span in the absence of GlcN, the life span-extending capabilities of GlcN were nullified in the presence of BHA or NAC. This indicates that the transient increase in ROS is required for the extension of life span caused by GlcN, thus providing additional support for adaptive ROS signaling or mitohormesis or both.” [References and Figures left out. Emphasis added]. Since the amount of BHA and NAC used were not given, it is difficult to discern whether the results were ordinary hormesis caused by too few antioxidants.

Recent Epidemiology Studies For Glucosamine and Chondroitin

Could glucosamine help you to ski into your ’80s?
Interestingly, two recent epidemiological studies on more than 77,000 individuals suggest that intake of glucosamine supplements is associated with reduced mortality in humans.5 In this study, antioxidants were found to not relate to increased mortality, but the variety used were low potency, and therefore unlikely to have any effect on longevity [See Durk & Sandy’s article “The Triage Theory of Aging” on page 20.] The strongest associations observed were between glucosamine and chondroitin use and total mortality where the use of each was associated with decreased risks of total mortality. The researchers suggested that the mechanism may involve antiinflammatory properties,


The study authors believe that anti-
oxidants interfere with glucosamine
life span extension. We don’t.


In the other epidemiology paper on glucosamine, also involving more than 77,000 subjects aged 50–76, glucosamine was associated with a significant decreased risk of death from cancer and with a large risk reduction for death from respiratory diseases. Use of glucosamine with or without chondroitin was associated with reduced total mortality and with reductions of several broad causes of death. In conclusion, those taking glucosamine were 13 per cent less likely to die over an eight-year period, than those who did not. Again, the researchers thought that the risk reduction by glucosamine and chondroitin was for the range of diseases associated with inflammation.6

Should We Now Start Taking Glucosamine Supplements?

Ristow replies: “This may be considered a valid option, and yes, I have started taking glucosamine myself.” However, he points out that, “diabetics should perform tight blood glucose control, especially during the first weeks.”7

About the epidemiology studies, Dr. Ristow said, “Unlike with our longer living mice, such an association is no definite proof of the effectiveness of glucosamine in humans.” Yet, he continued, “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.”


Given the safety of glucosamine, you
might consider increasing your dose.


Caution about Jumping to Conclusions

Tim Spector, a professor of genetic epidemiology at Kings College in London cautioned people against jumping to conclusions.8 “Glucosamine is an interesting molecule that could affect us subtly in many ways,” Spector said in a statement released by the Science Media Center in England. Dr. Spector was not involved in the Ristow study.

Continuing, “If an even modest effect on aging were proven it would be a major advance. However, humans are not the same as worms or rodents, and studies will need careful replication before we get over-excited,” he said.

Safety and Use Extension

If you are already taking glucosamine and chondroitin for joint relief, given the overwhelming safety of these nutrients, and the multiplicity of benefits demonstrated in several species (including humans), you might consider increasing your dose. It could prove to be a real bargain!

References

  1. Oh HJ, Lee JS, Song DK, Shin DH, Jang BC, Suh SI, Park JW, Suh MH, Baek WK. D-glucosamine inhibits proliferation of human cancer cells through inhibition of p70S6K. Biochem Biophys Res Commun. 2007 Sep 7;360(4):840-5.
  2. Weimer S, Priebs J, Kuhlow D, Groth M, Priebe S, Mansfeld J, Merry TL, Dubuis S, Laube B, Pfeiffer AF, Schulz TJ, Guthke R, Platzer M, Zamboni N, Zarse K, Ristow M. D-Glucosamine supplementation extends life span of nematodes and of ageing mice. Nat Commun. 2014 Apr 8;5:3563.
  3. Zarse K, Terao T, Tian J, Iwata N, Ishii N, Ristow M.Low-dose lithium uptake promotes longevity in humans and metazoans. Eur J Nutr. 2011 Aug;50(5):387-9.
  4. Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Blüher M. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. 2009 May 26;106(21):8665-70.
  5. Pocobelli G, Kristal AR, Patterson RE, Potter JD, Lampe JW, Kolar A, Evans I, White E. Total mortality risk in relation to use of less-common dietary supplements. Am J Clin Nutr. 2010 Jun;91(6):1791-800.
  6. Bell GA, Kantor ED, Lampe JW, Shen DD, White E. Use of glucosamine and chondroitin in relation to mortality. Eur J Epidemiol. 2012 Aug;27(8):593-603.
  7. The ETH Zurich. Glucosamine promotes longevity by mimicking a low-carb diet. https://www.ethz.ch/en/news-and-events/media-information/media-releases/2014/04/glukosamin-erhoeht-lebenserwartung.html. Published: April 8, 2014 Accessed: April 22, 2014.
  8. Morin M. Glucosamine promotes longevity in worms and mice, study says. The Los Angeles Times, April 8, 2014.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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