Could Glucosamine lead to a longer life? : LC Research/Media Forum : Active Low-Carber Forums

#1 ^

Wed, Apr-09-14, 06:31

RawNut

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Could Glucosamine lead to a longer life?

A food supplement made from crab shells could hold the key to a long life, according to scientists.

Tests on mice found glucosamine extended lifespan by almost 10 per cent – equivalent to an extra eight years in human terms.

It is thought the sugar-like supplement, which has long been used to keep joints healthy and ease the pain of arthritis, extends life by altering the metabolism.

Longer life: Researchers are recommending that people start taking glucosamine, pictured, after tests on ageing mice showed it to extend lifespan by almost ten per cent

The Swiss researchers said they could not be certain it would work in humans.

But scientist Michael Ristow, who has started taking glucosamine himself, claimed: ‘The chances are good.’

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Dr Ristow, of the Swiss Federal Institute of Technology in Zurich, is one of many scientists around the world hunting for an anti-ageing pill or potion. The challenges include finding one which is safe and that promises a healthy, as well as longer, old age.

New use: Glucosamine is normally used to treat arthritis

Dr Ristow first showed that giving worms glucosamine extended lifespan by 5 per cent. He then gave the supplement to ageing mice in addition to their usual diet.

These animals lived 10 per cent longer than a second group which ate normally, the journal Nature Communications reported.

The supplement, which can be bought in health food shops – in the form of a powder or more expensive capsules – also appeared to ward off diabetes. It is thought it lengthens life by switching the body’s energy supply from sugary carbohydrates to fat and protein.

Low-carbohydrate diets are known to have benefits to health including lowering weight, blood pressure and harmful blood fats.

In two large-scale human studies, people who took glucosamine lived longer than others – but Dr Ristow said more research is needed to prove its effectiveness.

He added: ‘This may be considered a valid option, and yes, I have started taking glucosamine myself.

‘There is no definite proof of the effectiveness of glucosamine in humans.

‘But the chances are good – and since unlike most other potentially lifespan-extending drugs there are no known relevant side-effects of glucosamine supplementation, I would tend to recommend this supplement.’

Dr Ristow advised people should take a daily tablespoon of glucosamine powder, mixed in water, or alternatively, 3g to 5g a day in capsule form.

Diabetics should speak to their doctor first, and people with shellfish allergies, or those on the blood-thinning drug warfarin, should be cautious.

Professor Tim Spector, of King’s College London, agreed that glucosamine is safe.

He said: ‘If an even modest effect on ageing 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.’

http://www.dailymail.co.uk/health/a...fe-8-years.html

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#2 ^

Wed, Apr-09-14, 10:05

RawNut

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Quote:

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).

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).
References:

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

suppversity.blogspot.com/2014/04/will-glucosamine-make-us-live-forever.html

#3 ^

Tue, Apr-15-14, 03:34

Demi

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Glucosamine promotes longevity by mimicking low-carb diet, study finds

Quote:

From Science Daily
April 8, 2014

Glucosamine promotes longevity by mimicking low-carb diet, study finds

Glucosamine has been freely available in drugstores for many decades. It is widely used to treat arthritis and to prevent joint degeneration. Moreover, glucosamine is known to delay cancer growth. In addition, glucosamine reduces metabolism of nutritive sugars, as was already shown some 50 years ago.

In 2007, Michael Ristow showed that too much nutritive sugar shortens the lifespan of roundworms, a widely studied model organism in aging research. Conversely, impairing carbohydrate metabolism in these worms was capable of extending lifespan. Unfortunately, the method used in worms at that time unexpectedly appeared to be ineffective in rodents, and hence was not studied further.

Extended lifespan by almost 10%

In the recently published study that was performed at ETH Zurich and four German research institutions, Ristow and his colleagues applied glucosamine to roundworms and found that they live around 5% longer than their untreated counterparts.

Next and most importantly, the researchers fed glucosamine to aging mice in addition to their normal diet. The mice were 100 weeks of age, reflecting a comparative human age of approximately 65 years. A control group of mice received no glucosamine while otherwise receiving an identical diet. Feeding the supplement to mice extended their lifespan by almost 10%, reflecting around 8 additional years of human lifespan. Moreover, glucosamine improved glucose metabolism in elderly mice indicating protection from diabetes, a life-threatening disease most prevalent amongst the elderly.

Mimicking a low-carb diet

Additional analyses revealed that glucosamine feeding promotes the breakdown of amino acids in both worms and mice. Amino acids are key components of proteins, and they become preferentially metabolized in the absence of carbohydrates. As Ristow points out, "this reflects the metabolic state of a low-carb diet due to glucosamine supplementation alone -- while these mice ingested the same amount of carbohydrates as their unsupplemented counterparts." This implies that glucosamine would mimic a low-carb diet in humans as well -- without the necessity of reducing the uptake of carbohydrates in our daily diet.

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." Interestingly, two recent epidemiological studies on more than 77,000 individuals suggest that intake of glucosamine supplements is associated with reduced mortality in humans. "Unlike with our longer living mice, such an association is no definite proof of the effectiveness of glucosamine in humans," says Ristow. He continues, "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."

Journal Reference:
Sandra Weimer, Josephine Priebs, Doreen Kuhlow, Marco Groth, Steffen Priebe, Johannes Mansfeld, Troy L. Merry, Sébastien Dubuis, Beate Laube, Andreas F. Pfeiffer, Tim J. Schulz, Reinhard Guthke, Matthias Platzer, Nicola Zamboni, Kim Zarse, Michael Ristow. D-Glucosamine supplementation extends life span of nematodes and of ageing mice. Nature Communications, 2014; 5 DOI: 10.1038/ncomms4563

http://www.sciencedaily.com/release...40408122135.htm

#4 ^

Tue, Apr-15-14, 04:01

M Levac

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So, they're saying low-carb extends life? Cynthia Kenyon already figured that out long ago. I wonder if glucosamine has the same effect on longevity if the diet is already low-carb.

#5 ^

Tue, Apr-15-14, 04:45

M Levac

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Scratch that. Cynthia's worms lived more than twice as long on low-carb alone. That's an order of magnitude longer than the 10% we could get from glucosamine, and this means even if glucosamine has an effect, it's insignificant compared to plain old low-carb. And the guy tried to sell it as if it was just like low-carb. Guffaws.

http://forum.lowcarber.org/showthread.php?t=454861

#6 ^

Tue, Apr-15-14, 07:02

teaser

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Just throwing this in here because it seems to be another connection between longevity and glucose metabolism.

http://www.benthamscience.com/open/...LSJ/22TOLSJ.pdf

Quote:

Oxaloacetic Acid Supplementation as a Mimic of Calorie Restriction

Abstract; The reduction in dietary intake leads to changes in metabolism and gene expression that increase lifespan, reduce the incidence of heart disease, kidney disease, Alzheimer's disease, type-2 diabetes and cancer. While all the molecular pathways which result in extended lifespan as a result of calorie restriction are not fully understood, some of these pathways that have resulted in lifespan expansion have been identified. Three molecular pathways activated by calorie restriction are also shown to be activated by supplementing the diet with the metabolite oxaloacetic acid. Animal studies supplementing oxaloacetic acid show an increase in lifespan and other substantial health benefits including mitochondrial DNA protection, and protection of retinal, neural and pancreatic tissues. Human studies indicate a substantial reduction in fasting glucose levels and improvement in insulin resistance. Supplementation with oxaloacetic acid may be a safer method to mimic calorie restriction than the use of traditional diabetes drugs.

For people less familiar with the Citric acid cycle, oxaloacetic acid and acetyl-CoA, the second produced mostly from the breakdown of fat or carbohydrate, are used to synthesize citric acid. Oxaloacetic acid can be produced from the glucose metabolite pyruvic acid. The cycle produces energy, consuming the "acetyl" in the process, and resynthesizing oxaloacetic acid. The major fates of the oxaloacetic acid are to continue around the cycle and continue to provide material for ATP production, or to be used to produce pyruvic acid--major substrate for gluconeogenesis.

http://www.ncbi.nlm.nih.gov/pubmed/19793063

Quote:

Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway.

Williams DS1, Cash A, Hamadani L, Diemer T.

Author information

Abstract

Reduced dietary intake increases lifespan in a wide variety of organisms. It also retards disease progression. We tested whether dietary supplementation of citric acid cycle metabolites could mimic this lifespan effect. We report that oxaloacetate supplementation increased lifespan in Caenorhabditis elegans. The increase was dependent on the transcription factor, FOXO/DAF-16, and the energy sensor, AMP-activated protein kinase, indicating involvement of a pathway that is also required for lifespan extension through dietary restriction. These results demonstrate that supplementation of the citric acid cycle metabolite, oxaloacetate, influences a longevity pathway, and suggest a tractable means of introducing the health-related benefits of dietary restriction.

http://www.ncbi.nlm.nih.gov/pubmed/23472183

Quote:

Malate and fumarate extend lifespan in Caenorhabditis elegans.
Edwards CB1, Copes N, Brito AG, Canfield J, Bradshaw PC.
Author information
Abstract
Malate, the tricarboxylic acid (TCA) cycle metabolite, increased lifespan and thermotolerance in the nematode C. elegans. Malate can be synthesized from fumarate by the enzyme fumarase and further oxidized to oxaloacetate by malate dehydrogenase with the accompanying reduction of NAD. Addition of fumarate also extended lifespan, but succinate addition did not, although all three intermediates activated nuclear translocation of the cytoprotective DAF-16/FOXO transcription factor and protected from paraquat-induced oxidative stress. The glyoxylate shunt, an anabolic pathway linked to lifespan extension in C. elegans, reversibly converts isocitrate and acetyl-CoA to succinate, malate, and CoA. The increased longevity provided by malate addition did not occur in fumarase (fum-1), glyoxylate shunt (gei-7), succinate dehydrogenase flavoprotein (sdha-2), or soluble fumarate reductase F48E8.3 RNAi knockdown worms. Therefore, to increase lifespan, malate must be first converted to fumarate, then fumarate must be reduced to succinate by soluble fumarate reductase and the mitochondrial electron transport chain complex II. Reduction of fumarate to succinate is coupled with the oxidation of FADH2 to FAD. Lifespan extension induced by malate depended upon the longevity regulators DAF-16 and SIR-2.1. Malate supplementation did not extend the lifespan of long-lived eat-2 mutant worms, a model of dietary restriction. Malate and fumarate addition increased oxygen consumption, but decreased ATP levels and mitochondrial membrane potential suggesting a mild uncoupling of oxidative phosphorylation. Malate also increased NADPH, NAD, and the NAD/NADH ratio. Fumarate reduction, glyoxylate shunt activity, and mild mitochondrial uncoupling likely contribute to the lifespan extension induced by malate and fumarate by increasing the amount of oxidized NAD and FAD cofactors.
PMID: 23472183 [PubMed

The "tail" end of the citric acid cycle goes fumarate-->malate-->oxaloacetate, so maybe no big surprise that all three give a longevity effect.

#7 ^

Tue, Apr-15-14, 18:31

WereBear

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All I can say is:

BWAHAHAHAHAHA! (like a villain)