11 replies to this topic

[ta5]

Am J Physiol Renal Physiol. 2014 Nov 19:ajprenal.00252.2014. 

Theobromine increases NAD+/Sirt1 activity and protects the kidney under diabetic conditions.

Papadimitriou A1, Silva KC1, Peixoto EB1, Borges CM1, Lopes de Faria JM1, Lopes de Faria JB2.

State University of Campinas

Reduction in sirtuin 1 (Sirt-1) is associated with extracellular matrix (ECM) accumulation in the diabetic kidney. Theobromine may reduce kidney ECM accumulation in diabetic rats. In the current study, we aimed to unravel, under diabetic conditions, the mechanism of kidney ECM accumulation induced by a reduction in Sirt-1 and the effect of theobromine in these events. In vitro, we used immortalized human mesangial cells (iHMCs) exposed to high glucose (HG, 30 mM), with or without small interfering RNA for NOX4 and Sirt1. In vivo, spontaneously hypertensive rats (SHR) were rendered diabetic by means of streptozotocin and studied after 12 weeks. The effects of treatment with theobromine were investigated under both conditions. HG leads to a decrease in Sirt-1 activity and NAD+ levels in iHMCs. Sirt-1 activity could be reestablished by treatment with NAD+, silencing NOX4, and poly (ADP-ribose) polymerase-1 (PARP-1) blockade, or with theobromine. HG also leads to low AMP/ATP ratio, acetylation of SMAD3 and increased collagen IV, which is prevented by theobromine. Sirt-1 or AMPK blockade abolished these effects of theobromine. In diabetic SHR rats, theobromine prevented increases in albuminuria and kidney collagen IV, reduced AMPK, elevated NADPH oxidase activity and PARP-1, and reduced NAD+ levels and Sirt-1 activity. These results suggest that in DM, Sirt-1 activity is reduced by PARP-1 activation and NAD+ depletion due to low AMPK, which increases NOX4 expression, leading to ECM accumulation mediated by transforming growth factor TGFβ-1 signaling. It is suggested that Sirt-1 activation by theobromine may have therapeutic potential for diabetic nephropathy.

PMID: 25411384

 

 

Darryl posted some other studies that mention theobromine and theophylline.

[tunt01]

 

 

In diabetic SHR rats, theobromine prevented increases in albuminuria and kidney collagen IV, reduced AMPK, elevated NADPH oxidase activity and PARP-1, and reduced NAD+ levels and Sirt-1 activity.

 

It took me a moment to realize that this sentence means theobromine prevents all of the following activities: increases in albuminuria/kidney collagen, prevents reduced AMPK, prevents elevated NADPH oxidase, etc.  

 

This was a really interesting datapoint.  Thanks for contributing this link, ta5.

[Gerrans]

I have become fascinated by theobromine in the last few days. I started drinking Cadbury's Bourneville cocoa recently--not for health reasons--not having drunk that sort of thing since childhood. Within a couple of days, I was hooked and choosing to drink it instead of coffee.

 

As far as coffee goes, I seem to need it but do not notice any stimulatory effect, presumably because I am conditioned to it. But this cocoa produced the stimulating effect that I theoretically associate with coffee. Looking up the components, I think it is likely that theobromine is responsible, because it is a similar type of substance to caffeine.

 

I did not look for a health benefit from Cadbury's Bourneville cocoa, because it is treated by the "dutching" process, which alkalises the cocoa to make it less bitter and in so doing knocks out most of the flavanols. From my experience, however, I am deducing that the theobromine--a xanthine--is not knocked out in the dutching process. If I am right, then the good news is that, for once, it might be possible to pleasantly access a useful compound without spending a load of money on supplements or fancy raw speciality foods.

 

One other thing I noticed is that my perpetually runny nose seems to have cleared up while drinking Bourneville. It could be a coincidence, but I notice that theobromine has been found to reduce coughing. Perhaps it helps against a runny nose in a connected way.

Edited by Gerrans, 22 November 2014 - 11:51 AM.

[ta5]

Looking up the components, I think it is likely that theobromine is responsible, because it is a similar type of substance to caffeine.

 

Theobromine is available as a concentrated powder, so you could find out. I tried it. I didn't like it, but it was part of the effect that I get from cocoa.

[Dstein]

Link to pdf download of paper: http://libgen.org/sc...enal.00252.2014

[Vastmandana]

Link to pdf download of paper: http://libgen.org/sc...enal.00252.2014

link not working, Dstein

[Dstein]

 

Link to pdf download of paper: http://libgen.org/sc...enal.00252.2014

link not working, Dstein

 

 

 

 

link not working, Dstein

 

Not sure why it isn't working, but if you go to libgen.org and in the field for "scientific article" enter the DOI: "10.1152/ajprenal.00252.2014" you'll be directed to a working download link for the PDF.

 

 

[APBT]

Try this:  http://ajprenal.phys...2.2014.abstract

[Dorian Grey]

Jeanne Calment was a big fan...  http://en.wikipedia..../Jeanne_Calment  "ate nearly one kilogram (2.2 lb) of chocolate every week"

 

Lived to 122!

Edited by synesthesia, 01 December 2014 - 12:14 AM.

[VERITAS INCORRUPTUS]

A study in healthy subjects would really be what is of interest to assess for potentials to exceed normal physiological levels.

 

The dose used was quite modest and practical:

 

Although the 8% of theobromine in 24 mg/kg of CL that the SHR rats received corresponds to 2 mg/kg of theobromine, we chose to treat them with 5 mg/kg. We made this decision because in the recent study in humans, the dose of theobromine was roughly 14 mg/kg (35), and it has been estimated that acute oral toxicity in rats is achieved with a much higher dose (950 mg/kg) (42). Therefore, 5 mg/kg of theobromine to treat rats is still quite a low dose

 

 

Jeanne Calment was a big fan...  http://en.wikipedia..../Jeanne_Calment  "ate nearly one kilogram (2.2 lb) of chocolate every week"

 

Lived to 122!

 

Most conventional chocolate (milk chocolate) consumed is very low in the actual components found in Theobroma Cacao itself (ie, theobromine et al.).  

[Gerrans]

A study in healthy subjects would really be what is of interest to assess for potentials to exceed normal physiological levels.

 

The dose used was quite modest and practical:

 

Although the 8% of theobromine in 24 mg/kg of CL that the SHR rats received corresponds to 2 mg/kg of theobromine, we chose to treat them with 5 mg/kg. We made this decision because in the recent study in humans, the dose of theobromine was roughly 14 mg/kg (35), and it has been estimated that acute oral toxicity in rats is achieved with a much higher dose (950 mg/kg) (42). Therefore, 5 mg/kg of theobromine to treat rats is still quite a low dose

 

 

Jeanne Calment was a big fan...  http://en.wikipedia..../Jeanne_Calment  "ate nearly one kilogram (2.2 lb) of chocolate every week"

 

Lived to 122!

 

Most conventional chocolate (milk chocolate) consumed is very low in the actual components found in Theobroma Cacao itself (ie, theobromine et al.).  

 

This is true. But something is making people need their fix of milk chocolate. If it were just the sugar or the milk in it, they would not have such cravings for chocolate in particular.
 

[Dorian Grey]

"Most conventional chocolate (milk chocolate) consumed is very low in the actual components found in Theobroma Cacao itself (ie, theobromine et al.)."

 

That's why you need a kilo/week if you want to live to 122!