Saturday, 12 January 2013

Ketones slow heart rate

Ketones slow heart rate, meanwhile short chain fatty acids increase heart rate. Both β-hydroxybutyrate and SCFA act through the receptor gpr41 to decrease or increase sympathetic nervous system activity, respectively. ( yes, much to everyone's surprise, BHB actually decreases sympathetic activity. )

Below are the graphs showing changes in heart rate in mice with infusion of either SCFA or BHB, note that gpr41-/- stands for mice that have knock-out of this receptor and so will not respond to the infusions.

On the left graph we see a gradual decline in heart-rate of wild-type mice in response to BHB infusion. On the right graph we see an increase in heart rate with Propionate infusion.

In contrast to BHB, the other ketone bodies acetoacetate and acetone had no affect on gpr41 acitvity, so BHB is the only ketone which decreases energy expenditure.

Something interesting is that the gpr41-/- mice had reduced body temperature. This is because without the gpr41 receptor the SCFA cannot act to increases the sympathetic nervous system, and so thermogenesis in response to feeding is diminished. ( they also report that ucp1 in brown adipose tissue was reduced in gpr41-/- so this is probably another reason for reduced body temp. )

Remember that BHB blocks gpr41, I had a weird idea flash in my head with this, ive seen alot of people complain of feeling cold on long term ketogenic dieting, and attribute it to reduced thyroid or whatever. This study suggests that increased serum ketones/BHB may be contributing to that decreased body temperature by antagonizing gpr41.

In theory this decline in body temperature can be reduced by consuming significant fibre that will go on to ferment in the colon to SCFA, and these SCFA increase sympathetic activity via the gpr41 receptor.

In theory,    that is.........

Heres another thing that comes to mind, the idea of carb refeeds to beat a weight loss plateau. Theres lots of theories as to how this works, including insulin and carbs bumping up leptin. Another idea could be the interplay between insulin and ketones on SNS activity.

Both ketones and insulin inhibit SNS activity, weight loss should be highest when SNS is highest. This must occur when both insulin and ketones are low. The situation of low insulin and low ketones will occur when you are transitioning from a high carb refeed back to a ketogenic state.

Once you have spent a few weeks in ketosis, insulin will be chronically low, ketones will be consistently elevated, and therefore SNS activity will be consistently depressed.


A link I found in the gpr41 paper goes here, where they say acetate, but not butyrate, stimulated leptin secretion from adipocytes. More good news for vinegar then I guess.

Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41).


  1. But is this effect of β-hydroxybutyrate not offset by the rise in epi/norepi? Clinical observation says that for most people ketosis raises SNS tone (insomnia, heart palps, anxiety) and eating carbs lowers it.

    Personally, I think carb refeeds work by spiking leptin, tricking the hypothalamus into thinking it's not famine season.

    1. Sidereal, im as confused as you with respect to the SNS :)

      Maybe the suppression of SNS by ketones only happens at higher blood concentrations than is typically seen with ketogenic dieting. *shrug*

  2. [aside] hey, Wooo -- come over here and discuss this!

  3. Relax guys she's probably working all weekend.

  4. LOL imagine what would happen if Guyenet actually had testicles and hadn't banned her. Oh my gawd. Heads would be rolling over there right now.

    1. i just think we'd be hearing an endless flow of static from Gunther. that guy doesn't know when to quit. ;-) ...yeah, i wish i knew which days she works -- make it easier to predict when she'll give us another flow of posts!