Allulose - any takers?

[TomBAvoider]

In a recent Peter Attia podcast (with Jocko Willink), he mentioned the sweetener allulose and made some pretty amazing sounding claims for it, to the effect that not only does it seem a superior sugar substitute, but as actually possibly having good physiological effects of lowering insulin and a few others. It sounded quite intriguing, although I admit, my natural scepticism leads me to think "too good to be true". Be that as it may, I went ahead and ordered some from Amazon, and am thinking of somehow incorporating a bit into my diet - the problem is that not only do I not use any added sugar in my diet, but I don't use any sweetener either. Furthermore, I wonder about dosing and protocol - always very important... anyone have any ideas as to what might be a good way to incorporate and at what dose and frequency? 

I also did a quick search of the boards here, and came up with a few places where it's discussed in the context of life extension, CR-mimetics and the like - eg:

https://www.mdpi.com/2072-6643/10/12/1821/htm

https://www.ncbi.nlm.nih.gov/pubmed/29317623

https://europepmc.org/abstract/med/29132732

There are also some interesting papers when I searched for "allulose" on PubMed.

[Gordo]

Fruit is the way to go. Homegrown today:

[Clinton]

Thanks Tom,

In the first paper you posted, one of the upstream compounds they examined was glucosamine - it's extremely safe, cheap and can buy at any walmart/costco.

Vince Giuliano has an excellent summary of it's effects here:

http://www.anti-agingfirewalls.com/2014/06/09/glucosamine-for-longevity/

He states: "Glucosamine appears to have a comparable or greater effect on mortality reduction and lifespan extension than Meformin, Rapamycin, 2DG, Veganism, and Resveratrol in nematodes and rodents."

This paper:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988823/

States (emphasis mine):

"d-Glucosamine (GlcN) is a freely available and commonly used dietary supplement potentially promoting cartilage health in humans, which also acts as an inhibitor of glycolysis. Here we show that GlcN, independent of the hexosamine pathway, extendsCaenorhabditis eleganslife span by impairing glucose metabolism that activates AMP-activated protein kinase (AMPK/AAK-2) and increases mitochondrial biogenesis. Consistent with the concept of mitohormesis, GlcN promotes increased formation of mitochondrial reactive oxygen species (ROS) culminating in increased expression of the nematodalamino acid-transporter 1(aat-1) gene. Ameliorating mitochondrial ROS formation or impairment ofaat-1-expression abolishes GlcN-mediated life span extension in an NRF2/SKN-1-dependent fashion. Unlike other calorie restriction mimetics, such as 2-deoxyglucose, GlcN extends life span of ageing C57BL/6 mice, which show an induction of mitochondrial biogenesis, lowered blood glucose levels, enhanced expression of several murine amino-acid transporters, as well as increased amino-acid catabolism. Taken together, we provide evidence that GlcN extends life span in evolutionary distinct species by mimicking a low-carbohydrate diet.”

 

https://academic.oup.com/ajcn/article/91/6/1791/4597416

"Conclusions: For most of the supplements we examined, there was no association with total mortality. Use of glucosamine and use of chondroitin were each associated with decreased total mortality."

 

[Saul]

Hi Tom!

My supermarket has been selling several products sweetened with allulose for several months; mostly high protein chocolate bars -- not exactly a health food.  Allulose is  a naturally occurring rare sugar, which is poorly digested by most people -- so it delivers less calories per gram than sucrose.  But anyone who consumes it doesn't know how many calories they are consuming (probably partly a function of your gut microbiota, I'd guess.  Most of us probably have a very healthy gut microbiome, so we would probably would absorb more calories)  It is also less not as sweet as sugar.  

A more interesting sweet substance is erythritol, a sugar alcohol.  This is sweet, and is not digested.  It is also not digested by mouth bacteria -- so it doen't promote tooth decay, like most sugars and sugar alcohols.  Many items sweetened with stevia also have some erythritol -- examples are chocolate bars manufactured by Lilly in the US, and Cavalier in Belgium.  These are hardly health foods -- baker's chocolate is high fat and high calorie.

I have found that my favorite sweetener is no sweetener -- I drink my home brewed Chinese white tea with no sweetener -- like green tea, it tastes best that way.

[mccoy]

Hi listened to that episode of Peter Attia's podcast, but really didn't remember about allulose. I then discovered that it's not allowed in Europe and, as a matter of fact, it's not sold by the domestic Amazon organization. It sounds promising though. 

Presently I consume stevia and erytritol, when I do not consume dark honey, my favourite sweetener. An issue with stevia and low-calories saweeteners is that they must be used sparingly adn dosed exactly, lest the taste becomes horribly sweet and cloying, in such cases I prefer to throw the food away. Also, not every food is compatible with stevia's aftertaste, although I must confess that Truvia (stevia + erythritol) tastes pretty good as a whole.

[Sibiriak]

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Clinton:   In the first paper you posted, one of the upstream compounds they examined was glucosamine - it's extremely safe, cheap and can buy at any walmart/costco.  Vince Giuliano has an excellent summary of it's effects...,

Thanks for bringing up glucosamine and the Giuliano article.  There doesn't seem to have been much discussion here on that topic.   From what I can tell,  glucosamine is a  promising anti-aging compound,  but the evidence for it, while intriguing,  is still rather sketchy.   Nevertheless,  because of its apparent safety  it might be a reasonable gamble.

Glucosamine: The new metformin? | Interview with Dr. Michael Ristow (2018)

http://geroscience.com/glucosamine-the-new-metformin-interview-with-dr-michael-ristow-part-ii/

 

Glucosamine Extends the Lifespan of Caenorhabditis elegans via Autophagy Induction (2018)

Tomoya Shintani, Yuhei Kosuge, Hisashi Ashida

https://www.jstage.jst.go.jp/article/jag/65/3/65_jag.JAG-2018_002/_html/-char/en

 

 

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DISCUSSION

Thus far, the most common strategy for promoting longevity is calorie restriction. An appropriate level of calorie restriction has been experimentally demonstrated to elongate the lifespan of various animal models such as rhesus monkeys, mice, fruit flies, and nematodes.³²⁾ On the other hand, the intake of certain exogenous factors has also been reported to induce longevity.³³⁾ These longevity-inducing factors include resveratrol, rapamycin, spermidine, and 2-deoxy-glucose. Most of these factors and calorie restriction have been found to induce autophagy; thus, autophagy has been recognized as one of the most important cellular mechanisms that prevent aging.³⁴⁾³⁵⁾ Resveratrol, a polyphenol found in red wine, can induce autophagy by activating sirtuin, an NAD⁺-dependent histone deacetylase.³²⁾ Rapamycin, an antibiotic produced by actinomycete, can directly inhibit TOR, which negatively regulates autophagy.³²⁾ Spermidine, a type of polyamine, can also induce autophagy through histone acetyltransferase inhibition in a dependent or independent manner.³⁶⁾ 2-Deoxy-glucose is a well known inhibitor of glycolysis that can deplete cellular ATP and act as a calorie restriction mimetic to induce autophagy.³⁷⁾³⁸⁾

We previously reported that GlcN could induce autophagy in mammalian cells via an mTOR-independent signaling pathway.²³⁾ In this study, we demonstrated for the first time that GlcN induced autophagy in the adults and embryos of C. elegans. We also found that GlcN supplementation extended the lifespan of the nematode. Recently, another group reported the longevity effect of GlcN on nematodes and mice.³⁹⁾ They suggest that the effect was caused by impaired glucose metabolism; however, the involvement of autophagy was not discussed. Here, we clearly showed that the longevity effect of GlcN required an autophagy gene, atg-18. However, unlike functional food factors and calorie restriction, the longevity genes sir-2.1 and daf-16 were not required for GlcN-induced lifespan extension.

GlcN is known to be incorporated into cells via glucose transporters and metabolized to UDP-GlcNAc through GlcN-6-phosphate.⁴⁰⁾ UDP-GlcNAc is used for the biosynthesis of O-linked GlcNAc, N-glycan, and GPI-anchor. Among these, O-linked GlcNAc is important modification of intracellular proteins required for regulating insulin signaling. Therefore, a high concentration of intracellular UDP-GlcNAc may induce autophagy. The increased synthesis of N-glycan precursors can also improve protein homeostasis and extend the lifespan of C. elegans.⁴¹⁾

An excess amount of GlcN-6-phosphate is metabolized to fructose-6-phosphate (an intermediate of glycolysis) and ammonia by glucosamine-6-phosphate deaminase. Intracellular ammonia has been reported to induce autophagy via UNC-51-like kinase 1 (ULK1)/ULK2-independent pathways.⁴²⁾ We found that mammalian cells cultured with ammonia induced autophagy in an mTOR-independent manner (unpublished data). However further studies would be needed to elucidate the autophagy-inducing mechanism of GlcN in terms of UDP-GlcNAc and/or ammonia.

Recently, non-metabolizable D-allulose, one of the rare hexoses, has been reported to extend the lifespan of nematodes.⁴³⁾ Similar to GlcN and 2-deoxy-glucose, D-allulose enters into cells through glucose transporters and inhibits glycolysis, inducing the metabolism of stored fat and mitochondrial respiration via AMP-activated protein kinase (AMPK). Increased respiration can cause the temporary formation of reactive oxygen species, leading to increased anti-oxidative enzyme activity, oxidative stress resistance, and survival rates.⁴³⁾⁴⁴⁾ Orally administrated GlcN has also been reported to affect carbohydrate metabolism and reduce body fat in rodents,⁴⁵⁾ and it could contribute to enhanced oxidative stress resistance followed by AMPK activation.³⁹⁾ Therefore, the mechanism of the anti-aging effect of GlcN may be partially similar to that of D-allulose and 2-deoxy-glucose.

GlcN is widely consumed as a dietary supplement to promote cartilage health; however, its efficacy remains controversial. A large-scale epidemiological study on the long-term intake of various dietary supplements has revealed that the use of GlcN or chondroitin could significantly reduce mortality.⁵⁾ Despite its limitations, the results of this study were consistent, to some extent, with those of the epidemiological study. Therefore, GlcN may exert anti-aging effects by inducing autophagy in humans.

 

Glucosamine-Induced Autophagy through AMPK–mTOR Pathway Attenuates Lipofuscin-Like Autofluorescence in Human Retinal Pigment Epithelial Cells In Vitro (2018)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983587/

 

Association of habitual glucosamine use with risk of cardiovascular disease (2019)

https://www.ncbi.nlm.nih.gov/pubmed/31088786

 

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CONCLUSION: Habitual use of glucosamine supplement to relieve osteoarthritis pain might also be related to lower risks of CVD events

.

Michael Rae's "Crazy Supplement Regime"

https://www.longecity.org/forum/stacks/stack/122-michaels-tiered-supplement/

 

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[...]Glucosamine appears to slightly extend the lifespan of middle-aged mice,((49), although they only report the survival curve and statistical significance of the differences in mean (?) and maximum lifespan in the mice, without giving the mean and maximum lifespans of the various groups quantitatively — and the survival curve suggests a lot of early mortality): (51)
 
Additionally,

Current use of glucosamine was associated with a significant decreased risk of death from cancer (HR 0.87 95% CI 0.76-0.98) and with a large risk reduction for death from respiratory diseases (HR 0.59 95% CI 0.41-0.83) (Pocobelli et al., 2010; Bell et al., 2012). Glucosamine supplementation [was associated with a] decrease risk of lung cancer in humans (Brasky et al., 2011). A meta-analysis has shown that glucosamine has lowest risk of adverse effects compared with other treatments (Diarecin and NSAIDs) (Kongtharvonskul et al., 2015). The oral supplementation of glucosamine can potentially improve cutaneous aging in human and reduce the appearance of visible wrinkles and fine lines of the skin (Murad & Tabibian, 2001).(52)

Most of these effects, including that on colorectal cancer, were seen in the VITAL study in Washinton state; the association with reduced colon cancer risk was seen independently in the Nurses' Health Study and Health Professionals Follow-up Study.(53) I recommend glucosamine sulfate 2KCl, not the cheaper glucosamine hydrochloride.
 
However, prompted by Florin, I have just (2018-07-27) noted two studies (60,61) finding that glucosamine supplementation raises intraocular pressure (IOP), the main driver of glaucoma. (60),  which is more robust in design, only finds a rise because of a mixture of a lower baseline (reversion to the mean?) and some post hoc fiddling, and "Although mean rise of IOP was statistically significant in the glucosamine group, more than 2 mm Hg rise in IOP was also more in the treatment group (34% of those receiving treatment vs 12.5% of patients on placebo)." And it was done in Iran.
 
However, even a suggestion of a risk may not be worth it to some people, especially if their inflammation is already low or they have reason to think they're at risk of glaucoma.

Quote

More recently PMID 31104873 reported out "Effect of glucosamine sulfate on intraocular pressure in patients with knee osteoarthritis: A prospective randomized controlled trial," an open trial of 42 subjects finding "no differences in the IOPs between the groups (P>0.05) nor differences in baseline IOPs within each group compared with each follow-up visit (P>0.05)" between subjects receiving "1500mg of crystalline glucosamine sulfate once daily for 6 months [vs. controls]... at 6 weeks, 3 months, 6 months, and 9 months," which is a larger trial than the previous reports, but it's still small, was unblinded (ha ha), and was carried out in Thailand, where standards may not be as good. I'd also like to know the role of any sponsor in the trial, which isn't disclosed in the abstract and unfortunately I've not been able to acquire the full text.

 

Quote

Here's some more bad news about glucosamine: it has bad effects in both the normal and injured intervertebral discs of animal models, and at least in vitro, there are other problems associated with glucosamine.

Effects of Oral Glucosamine on Intervertebral Disc Matrix in an Animal Model
https://www.thespine...0776-0/abstract

 Glucosamine supplementation demonstrates a negative effect on intervertebral disc matrix in an animal model of disc degeneration.
https://www.ncbi.nlm...pubmed/23324939

 Glucosamine promotes longevity by mimicking a low-carb diet
https://www.longecit...-low-carb-diet/

Edited September 6, 2019 by Sibiriak

[mccoy]

Glucosamine I did found on the domestic Amazon network, actually there is lots of glucosamin and chondroitin sulphate with MSM. Reading the above references posted by Sibiriak though does not encourages me to order any.

[Saul]

My local supermarket (the flagship Wegman's) showcased a new protein bar sweetened primarily with allulose -- a version of the Hero bar.  The nutrition info on the bar listed the allulose as having the same calories, per gram, as sucrose -- but included a disclaimer that this was required by FDA regulations, claiming (probably correctly) that the actual calories were lower.

There are many reasons why I wouldn't eat this thing (very high protein, worthless carbs) -- but I did look up allulose in Wikipedia.  Wikipedia indicated that it varies from 1/2 the calories absorbed from a comparable amount of sucrose, to a lot more -- varying by individual.

Allulose is sold on Amazon -- I wouldn't buy it.

  --  Saul

[Ron Put]

22 hours ago, mccoy said:

Glucosamine I did found on the domestic Amazon network, actually there is lots of glucosamin and chondroitin sulphate with MSM. Reading the above references posted by Sibiriak though does not encourages me to order any.

I take both glucosamine and MSM and IMO glocosamine is overall beneficial.

Allulose? I personally don't see the point.

[Sibiriak]

Oral Administration of Glucosamine Improves Vascular Endothelial Function by Modulating Intracellular Redox State. (2017)

 

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Abstract

Glucosamine, used to treat osteoarthritis, has been shown to have anti-inflammatory and anti-atherosclerotic effects in experimental studies. A recent cohort study has demonstrated that the use of glucosamine was significantly associated with decreased total mortality. Vascular endothelial function is a potent surrogate marker of atherosclerosis and cardiovascular mortality where oxidative stress could participate. Therefore, we investigated whether glucosamine improves vascular endothelial function and intracellular redox state. We examined the effects of oral glucosamine administration (3000 mg/day) for 4 weeks on flow-mediated vasodilation (FMD) and intraerythrocyte glutathione parameters in 20 volunteers. Nineteen age-matched volunteers served as controls.

Glucosamine administration significantly increased FMD (from 7.0 ± 2.3 to 8.7 ± 2.3%, P = 0.022). In the control group, FMD did not change. Glucosamine administration significantly increased intraerythrocyte total glutathione levels (from 212.9 ± 46.2 to 240.6 ± 49.4 μmol/L, P = 0.006), intraerythrocyte reduced form of glutathione (GSH) levels (from 124.7 ± 42.6 to 155.2 ± 47.7 μmol/L; P = 0.004) and intraerythrocyte GSH/oxidized form of glutathione (GSSG) ratios (from 3.18 ± 1.64 to 3.88 ± 1.61, P = 0.04). In the control group, any glutathione parameters did not change. Moreover, a stepwise multivariate analysis revealed percent change of GSH/GSSG is the only independent predictor for those of FMD (standardized β = 0.58, P = 0.007) in the glucosamine group. Glucosamine administration improved FMD in association with amelioration of intraerythrocyte GSH/GSSG ratios. These results suggest that oral glucosamine administration might improve vascular endothelial function by modulating intracellular redox state.

 

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In conclusion, the present study provides the first demonstration in humans that glucosamine improves vascular endothelial function by modulating intracellular redox balance. Thus, glucosamine might have anti-atherosclerotic properties, possibly through the improvement of endothelial function induced by the antioxidant capacity. Further randomized studies with a large number of participants for a longer duration should be performed to determine whether long-term administration of glucosamine would prevent cardiovascular events

 

[mccoy]

On 9/7/2019 at 9:15 PM, Ron Put said:

I take both glucosamine and MSM and IMO glocosamine is overall beneficial.

How did you determine if it is beneficial? 

[Ron Put]

I used to give a very expensive (at the time) veterinarian version (Cosequin, or something) of it in the 1990s to an old dog, and it appeared to help her walk a little better. I started taking it much later mostly as a prophylactic and because I had read a few mentions that glucosamine has cardio benefits. I take it probably six-nine months out of the year -- there are no known long term deleterious effects, so I figure at worst I wasted my money.

Here is a summary:

https://supplementclarity.com/glucosamine-heart-disease-review/

[mccoy]

I just remember that examine.com by kamal patel is a pretty exhaustive reference on supplements. I'm interested into the joint health aspect of glucosamine.

https://examine.com/supplements/glucosamine/