16 replies to this topic

[brosci]

While eating a high fat diet, I find that I can keep blood sugar very low for extended periods.  Without doing much else other than eating clean foods based around meat+veg, my A1C stays near the 4.5-4.9% range with glucose consistently under 100 mg/dL.  However, I would like to have days with a higher intake of carbohydrate.  The side effect from always keeping glucose so low is that it can take several days of increased carbohydrate intake to upregulate insulin stores and decrease the glucose-sparing fat-burning adaptation within muscle tissue.  If I go straight from ketosis into eating something like oats, my blood sugar will almost double.

 

I've read that Maqui berries can increase insulin to decrease post-prandial glucose.  I believe Alpha-Lipoic Acid is also quite useful for glucose disposal purposes, increasing uptake and acting as an insulin mimetic.  Whey protein is also fairly insulinogenic.

 

What are other useful supplements / regimens for this purpose?  What's the most safe and effective stack?

Edited by brosci, 29 June 2016 - 09:03 PM.

[thedevinroy]

Any AMPK activator. Jiaogulan, ALA, aged garlic, green tea, quercetin, and obviously metformin is the big one.

https://selfhacked.c...mpk-activators/

Pretty detailed look. I'm definitely one who gets a bit of fatigue with the wrong combination of AMPK activators, so it makes sense to also take alongside something lifting like cocoa or coffee or an electrolyte drink.

Edited by devinthayer, 29 June 2016 - 09:31 PM.

[brosci]

Any AMPK activator. Jiaogulan, ALA, aged garlic, green tea, quercetin, and obviously metformin is the big one.

https://selfhacked.c...mpk-activators/

Pretty detailed look. I'm definitely one who gets a bit of fatigue with the wrong combination of AMPK activators, so it makes sense to also take alongside something lifting like cocoa or coffee or an electrolyte drink.

Very informative list!  I've read Fenugreek is useful, as well as Pterostilbene + Phloridzin which aren't on that list.  Quercetin sounds like an potential candidate, although I read it's an MAO inhibitor?

 

I read this about ALA:

http://examine.com/s...ha-Lipoic Acid/

Regular, long term supplementation may cause liver damage, and should be considered with caution. Both short and long term ALA treatment increased liver cholesterol content by 70% and 110%, respectively, and increased triglyceride levels, inducing systemic triglyceridemia. Moreover, in spite of the fact that short term ALA treatment decreased lipogenic gene expression, it also caused fat accumulation in the liver. Long-term ALA treated mice showed a worse phenotype, with extensive fat accumulation leading to hepatic steatosis and extensive liver damage. Long-term ALA treatment in healthy animal models may be liver toxic, causing a phenotype that closely resembles that of non-alcoholic fatty liver disease. It should be noted that the dose of ALA in the healthy mouse study of 20mg/kg is equivalent to approximately 1.8 grams/day in a 200 lb human. Although this is a relatively high dose of ALA, it is close enough to standard doses that caution may be warranted for long term supplementation.

 

I'm currently using Jarrow's brand of "Bio-Enhanced" Na-R-ALA, which is listed as increasing serum levels 40x over the standard form of ALA.  It's quite effective for me:

https://geronova.com...of-lipoic-acid/

 

I'm curious if some of these might be more effective (and safer?) than others or synergistic.

Edited by brosci, 29 June 2016 - 10:05 PM.

[brosci]

This is also an interesting tidbit on jiaogulan:

https://examine.com/...a-pentaphyllum/

"There seems to be a motif where preloading and chronic loading is very protective at low doses, and acute supplementation or rehabilitation (taking the supplement after the stressor) appears to be less effective."

 

Would it make sense then to take an AMPK activator before exercise (the stressor) as a pre-workout, followed by something like ALA (+ Whey?) to further encourage glucose uptake?

Edited by brosci, 29 June 2016 - 11:48 PM.

[brosci]

Isoleucine + glutamine also looks like an interesting combo:

https://examine.com/...ucine/#summary3

http://www.mdpi.com/...43/7/4/2101/htm

 

I was reading that ALA might present some chelation concerns (liberating mercury and delivering it to neural tissue?)

Edited by brosci, 04 July 2016 - 04:09 AM.

[vader]

milk thistle is as good as metformin

[brosci]

Inositol, Biotin (currently stacked with my Na-R-ALA supplement), and Taurine are also looking like interesting supplements:

 

Inositol:

https://examine.com/...sitol/#summary5

 

Biotin:

https://examine.com/...tin/#summary6-1

 

Taurine:

http://www.ncbi.nlm....pubmed/11787643

http://scielo.isciii...112010000600004

 

Chromium / Vanadium are often mentioned to increase insulin sensitivity and assist with glucose disposal, however I've also read that there might be pro-oxidative concerns: https://www.scienced...60111121443.htm

 

I would be curious to read how something like Whey protein compares with BCAAs vs EAAs or some other isoleucine mix for glucose uptake:

http://suppversity.b...ate-muscle.html

 

I've read intermittent fasting, cold showers, and pre-breakfast exercise (particularly sprints / HIIT and heavy compound exercise) increase AMPK and potentiate glucose uptake, then a post-prandial walk or lightly aerobic exercise immediately following a meal further seems to attenuate peak glucose concentrations.

 

Perhaps something like a large fast between dinner and breakfast with a pre-workout AMPK activator could be utilized before heavy exercise (sprints + compound lifts).  Exercise could be performed with intra-workout BCAAs+Glutamine, followed by a post-workout cold shower to set the stage for maximal glucose disposing potential.  This carbohydrate-rich post-workout breakfast meal could be spiked with Whey or EAAs and some insulin mimetic stack (something like CinnulinPF x Biotin x ALA x Taurine x Bitter Melon?) followed by a brisk walk.  Perhaps this could be packed into a smoothie for a PWO sip-and-walk or bike ride.

 

Although, if this is done too well, I suppose hypoglycemia would ensue...

 

This is an interesting table of plants having insulin mimetic or insulin secreatory activity: 

http://www.ncbi.nlm....-02-04-320-t02/

Edited by brosci, 06 July 2016 - 11:05 PM.

[thedevinroy]

Any AMPK activator. Jiaogulan, ALA, aged garlic, green tea, quercetin, and obviously metformin is the big one.

https://selfhacked.c...mpk-activators/

Pretty detailed look. I'm definitely one who gets a bit of fatigue with the wrong combination of AMPK activators, so it makes sense to also take alongside something lifting like cocoa or coffee or an electrolyte drink.

Very informative list! I've read Fenugreek is useful, as well as Pterostilbene + Phloridzin which aren't on that list. Quercetin sounds like an potential candidate, although I read it's an MAO inhibitor?

I read this about ALA:
http://examine.com/s...ha-Lipoic Acid/

Regular, long term supplementation may cause liver damage, and should be considered with caution. Both short and long term ALA treatment increased liver cholesterol content by 70% and 110%, respectively, and increased triglyceride levels, inducing systemic triglyceridemia. Moreover, in spite of the fact that short term ALA treatment decreased lipogenic gene expression, it also caused fat accumulation in the liver. Long-term ALA treated mice showed a worse phenotype, with extensive fat accumulation leading to hepatic steatosis and extensive liver damage. Long-term ALA treatment in healthy animal models may be liver toxic, causing a phenotype that closely resembles that of non-alcoholic fatty liver disease. It should be noted that the dose of ALA in the healthy mouse study of 20mg/kg is equivalent to approximately 1.8 grams/day in a 200 lb human. Although this is a relatively high dose of ALA, it is close enough to standard doses that caution may be warranted for long term supplementation.

I'm currently using Jarrow's brand of "Bio-Enhanced" Na-R-ALA, which is listed as increasing serum levels 40x over the standard form of ALA. It's quite effective for me:
https://geronova.com...of-lipoic-acid/

I'm curious if some of these might be more effective (and safer?) than others or synergistic.

"Systemic triglyceridemia" is a made up phrase. I think what that article on ALA was trying to get at was that there is a lot more research to be done on supplements before we start going HAM on something nature deems almost insignificant. It looked at how humans typically mass consume ALA.

The study needs to be repeated to be verified, but I would say yes sir we have a problem with racemic and unstableness versions of ALA which are quite heavy on the liver. Liver toxicity is caused by liver inefficiencies. I do believe that the stabilized R-ALA you are taking is much easier on the liver.

ALA does increase glycogen storage, so as how to use it, use it like you are shoving glucose into your liver. Between workouts. Then you can theoretically work out for longer without getting exhaustion. Since your brain uses 20% of your daily glucose, you might also consider it a supplement to use the day before fasting.

Edited by devinthayer, 06 July 2016 - 10:44 PM.

[brosci]

"Systemic triglyceridemia" is a made up phrase. I think what that article on ALA was trying to get at was that there is a lot more research to be done on supplements before we start going HAM on something nature deems almost insignificant. It looked at how humans typically mass consume ALA.

The study needs to be repeated to be verified, but I would say yes sir we have a problem with racemic and unstableness versions of ALA which are quite heavy on the liver. Liver toxicity is caused by liver inefficiencies. I do believe that the stabilized R-ALA you are taking is much easier on the liver.

ALA does increase glycogen storage, so as how to use it, use it like you are shoving glucose into your liver. Between workouts. Then you can theoretically work out for longer without getting exhaustion.

 

My main concern with ALA is chelation, then reabsorption of heavy metals:

http://www.altmedrev...ons/7/6/456.pdf

 

There was disconcerting evidence from this study, however, that ALA may also alter the tissue distribution of mercury and other heavy metals. Although levels of inorganic mercury and methylmercury in the kidney dropped significantly, levels of inorganic mercury also increased significantly in the brain, lung, heart, and liver tissue. Methylmercury levels had also increased in the brain, intestine and muscle of the rats given ALA. The same phenomenon occurred in rats exposed to cadmium and given the same doses of ALA. Levels of cadmium in the liver dropped (where cadmium is most frequently stored) but increased in the kidney and muscle. The same was true in rats given copper and ALA; all tissues examined had increased levels of copper, except for the liver (where copper usually accumulates) where levels had dropped. In all cases the pattern was the same; the tissues that concentrated the metal (blood, spleen, and kidneys in the case of methylmercury) had reduced concentrations, while other tissues appeared to have a greater concentration.

 

The evidence that ALA may mobilize heavy metals to other tissues from tissues where the metals are most concentrated, specifically the brain, is troublesome. 

While I don't eat much mercury-rich seafood per se, I do eat a lot of seafood (several times a week) which overall tends to be rich in mercury compared with other foods.  I also consume a lot of very dark chocolate and cacao powder, rich in cadmium.

Edited by brosci, 06 July 2016 - 11:19 PM.

[thedevinroy]

 

"Systemic triglyceridemia" is a made up phrase. I think what that article on ALA was trying to get at was that there is a lot more research to be done on supplements before we start going HAM on something nature deems almost insignificant. It looked at how humans typically mass consume ALA.

The study needs to be repeated to be verified, but I would say yes sir we have a problem with racemic and unstableness versions of ALA which are quite heavy on the liver. Liver toxicity is caused by liver inefficiencies. I do believe that the stabilized R-ALA you are taking is much easier on the liver.

ALA does increase glycogen storage, so as how to use it, use it like you are shoving glucose into your liver. Between workouts. Then you can theoretically work out for longer without getting exhaustion.

 

My main concern with ALA is chelation, then reabsorption of heavy metals:

http://www.altmedrev...ons/7/6/456.pdf

 

There was disconcerting evidence from this study, however, that ALA may also alter the tissue distribution of mercury and other heavy metals. Although levels of inorganic mercury and methylmercury in the kidney dropped significantly, levels of inorganic mercury also increased significantly in the brain, lung, heart, and liver tissue. Methylmercury levels had also increased in the brain, intestine and muscle of the rats given ALA. The same phenomenon occurred in rats exposed to cadmium and given the same doses of ALA. Levels of cadmium in the liver dropped (where cadmium is most frequently stored) but increased in the kidney and muscle. The same was true in rats given copper and ALA; all tissues examined had increased levels of copper, except for the liver (where copper usually accumulates) where levels had dropped. In all cases the pattern was the same; the tissues that concentrated the metal (blood, spleen, and kidneys in the case of methylmercury) had reduced concentrations, while other tissues appeared to have a greater concentration.

 

The evidence that ALA may mobilize heavy metals to other tissues from tissues where the metals are most concentrated, specifically the brain, is troublesome. 

While I don't eat much mercury-rich seafood per se, I do eat a lot of seafood (several times a week) which overall tends to be rich in mercury compared with other foods.  I also consume a lot of very dark chocolate and cacao powder, rich in cadmium.

 

 

I wish there was a way to know for sure your lifespan, calculate the potential mercury accumulation based on regular ALA consumption.  I can't say for sure that.  However, that paper goes over two different chelating agents that counteract the effects of ALA in that area: DMPS and DMSA.  If you're worried, take those scientists' recommendations.

[brosci]

It sounds like Benfotiamine could be another useful one to add to the list:

https://examine.com/...amine/#summary5

 

http://www.ncbi.nlm....pubmed/21984258

"Benfotiamine significantly increased glucose oxidation under normoglycemic (35 and 49% increase at 100 and 200 μM benfotiamine, respectively) as well as hyperglycemic conditions (70% increase at 200 μM benfotiamine). Benfotiamine also increased glucose uptake. "

 

Prickly Pear Extract is also interesting:

http://www.ncbi.nlm....les/PMC3238149/

[brosci]

Agmatine looks interesting as well, as an intra-workout NO booster and glucose uptake promoter:

https://examine.com/...ments/agmatine/

 

 

Agmatine can act upon the adrenal glands (via the imidazoline receptors) to release β-endorphin, an opioid that can dispose of glucose from the blood into skeletal muscle tissue.  β-endorphin has elsewhere been noted to inhibit hepatic glucose production while inducing insulin secretion from the pancreas.

 

[plainzero]

milk thistle is as good as metformin

 

 Berberine seems like the supplement most often compared to metformin.

[brosci]

Interestingly, ketone supplementation appears to improve glucose uptake with a doubling of endogenous insulin:

http://suppversity.b...-t-booster.html

 

There is increased glucose uptake and higher muscle glycogen following ketone supplementation in man, beyond levels achievable by high-dose intravenous glucose infusion, study shows. "The additional novel finding of a doubling of endogenous insulin has significant implications for the augmentation of exercise recovery and anabolic metabolism," the authors point out excitedly after observing that the 12 servicemen underwent a validated interval protocol to deplete muscle glycogen consuming randomly higher a control drink + intravenous carbohydrate(Cont-CHO), ketone drink + intravenous carbohydrate(Ket-CHO) or control drink + intravenous saline(Cont-saline) showed 33% higher whole body glucose disposal 125.8(±4.2) vs. 94.7(±3.2) g, for Ket-CHO vs Cont-CHO (p<0.000001), had increased muscle glycogen 246(±32.4) vs 164(±12.5) mmol glycosyl units/kg dry weight of muscle (p=0.017) and doubled insulin levels: 31.1(±5.7) vs 16.4(±2.7) mU/L (p<0.01) for Ket-CHO vs Cont-CHO.

 

 

I'm curious if C8 MCT oil (pre or post-workout?) would have a similar effect via increased BHB.

[ta5]

Here's a link to the ketones study full text, but I only see an abstract, I guess because it was a presentation.

 

The increase in insulin would explain the increase in glucose disposal.

I'm afraid doubling insulin would contribute to insulin resistance.

We want things that increase glucose disposal without increasing insulin. 

 

Am I missing something?

[brosci]

Here's a link to the ketones study full text, but I only see an abstract, I guess because it was a presentation.

 

The increase in insulin would explain the increase in glucose disposal.

I'm afraid doubling insulin would contribute to insulin resistance.

We want things that increase glucose disposal without increasing insulin. 

 

Am I missing something?

 

Currently, I'm fasted for around 75% of each day, and I'm in ketosis for 85% of the week or so through a HFLC diet + IF with 1x refeed/wk.  (I might bump this up to just a LC diet with 1-2x refeeds/wk and loosen my eating window closer to 8-12hrs rather than 4-6.)  There's not much insulin going on outside of when I specifically want to use more insulin to shuttle large volumes of carbohydrates into glycogen stores.

 

I generally exercise fasted, and then look to starchy carbohydrates for insulin signaling & muscle protein synthesis / topping of glycogen stores / increasing leptin & thyroid hormones.  It doesn't seem like 2 meals with 2x the insulin (which will be moving 10 times the amount of carbohydrate as my usual 10-20g carbohydrate meals) would necessarily contribute to insulin resistance.  Chronic T2D IR seems to be more related to consistently elevated insulin levels and uncontrolled elevated blood sugar levels -- the last time I looked into checking fasted serum insulin, it was below the minimum amount detectable in blood (red flag on the test) and blood sugar was flagged yellow bordering on hypoglycemia.

[ta5]

If you want to increase insulin, you can inject it, or there are several other insulin secretagogues to choose from.