Timing of supplements: empty stomach or food? Combinations?

[Stavia]

Thanks Hill. It doesn't actually say it competes tho, just that it's the same transport protein.

[hill dweller]

I've decided to suspend the multivitamin from my stack. Here's why:
1. Adequate dietary intake of fat solubles (A, E, et al)
2. Adequate dietary intake of stuff that could be harmful in excess: calcium, C
3. Most B family vitamins are not recommended form. Examples include B9 (folic acid instead of 5-MTHF), B12 (not methylcobalamin), nB5, B3 (no B3a).
4. Probiotic with soil-based prebiotics supplies trace elements.
5. Multivitamin's form of K is K1 (supplied via diet), not MK-2 & MK-4
6. Combination of Ca with K with Mg
7. Already supplementing with much of what's in the multi, in better form. One less pill to swallow, too.

Regarding forms of folate and possible toxicity of folic acid: https://ods.od.nih.gov/factsheets/Folat ... fessional/

[SusanJ]

Good caution on many of the multis out there, Hill. It is hard, but not impossible to find the "right" versions of vitamins. Definitely have to do the research if you want to use a multi.

[aphorist]

except the alpha lipoic acid which I take fasting.

The timing of Lipoic Acid is something I have been thinking about lately.

I'm of the current opinion that Lipoic Acid should be taken with food, as it acts as an insulin mimetic.

I'm not sure that everyone should view this issue the same, but at least for me, improved GLUT functionality, and reduction of de novo lipogenesis (in favor of glycogen synthesis) seems to be a benefit of Lipoic Acid. [1, 4] I think BACE1 overexpression, which is a common occurrence in ALZ, inhibits the pyruvate dehydrogenase complex (PDH) and lipoic acid seems to provide a protective role against this. [2] Lipoic acid is a co-factor for PDH and alpha-ketoglutarate dehydrogenase for the acyl transferase activity.

If ALZ is functionally a Type 3 diabetes where neurons are starving due to a breakdown of glycolytic behavior (pre-TCA cycle), then improving glucose metabolism (during food consumption) should alleviate this and I think that's how Lipoic Acid plays an ameliorating role. If you look at Findlay Fig. 6F http://www.ncbi.nlm.nih.gov/pmc/article ... figure/F6/, you can see the improved glucose oxidation with increasing lipoic acid levels.

Given that lipoic acid has a peak plasma value of approximately 0.56 hrs (~30 minutes) [5], my thought is that a pulsatile usage with food might be best.

I think some of the longevity studies in mice, which find no benefit to Lipoic Acid [4], suffer from the problem that lipoic acid is constantly being given as a percentage of water intake and not taken in a circadian rhythmic fashion. I'm not 100% sure on this issue yet.


1. Butler JA, Hagen TM, Moreau R. Lipoic acid improves hypertriglyceridemia by stimulating triacylglycerol clearance and downregulating liver triacylglycerol secretion. Arch Biochem Biophys. 2009;485(1):63-71.

2. Findlay, J., Hamilton, D., & Ashford, M. (2015). BACE1 activity impairs neuronal glucose oxidation: rescue by beta-hydroxybutyrate and lipoic acid.Frontiers In Cellular Neuroscience, 9. doi:10.3389/fncel.2015.00382

3. Lee CK, e. (2004). The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice. - PubMed - NCBI . 

4. Pashaj A, e. (2016). α-Lipoic acid as a triglyceride-lowering nutraceutical. - PubMed - NCBI . Ncbi.nlm.nih.gov. Retrieved 25 January 2016, from http://www.ncbi.nlm.nih.gov/pubmed/26235242

5. Teichert, J., Hermann, R., Ruus, P., & Preiss, R. (2003). Plasma Kinetics, Metabolism, and Urinary Excretion of Alpha-Lipoic Acid following Oral Administration in Healthy Volunteers.The Journal Of Clinical Pharmacology,43(11), 1257-1267. doi:10.1177/0091270003258654

[Stavia]

Thank you aphorist! Very helpful thoughts.
I have been taking it before work as a cognitive inhancer thingy, I do feel more alert with it (?placebo?) and I don't eat until 12 noon. Guess I could take it with to work and take it with my first meal.

[apod]

except the alpha lipoic acid which I take fasting.

The timing of Lipoic Acid is something I have been thinking about lately.

I'm of the current opinion that Lipoic Acid should be taken with food, as it acts as an insulin mimetic.

I'm not sure that everyone should view this issue the same, but at least for me, improved GLUT functionality, and reduction of de novo lipogenesis (in favor of glycogen synthesis) seems to be a benefit of Lipoic Acid. [1, 4] I think BACE1 overexpression, which is a common occurrence in ALZ, inhibits the pyruvate dehydrogenase complex (PDH) and lipoic acid seems to provide a protective role against this. [2] Lipoic acid is a co-factor for PDH and alpha-ketoglutarate dehydrogenase for the acyl transferase activity.

If ALZ is functionally a Type 3 diabetes where neurons are starving due to a breakdown of glycolytic behavior (pre-TCA cycle), then improving glucose metabolism (during food consumption) should alleviate this and I think that's how Lipoic Acid plays an ameliorating role. If you look at Findlay Fig. 6F http://www.ncbi.nlm.nih.gov/pmc/article ... figure/F6/, you can see the improved glucose oxidation with increasing lipoic acid levels.

Given that lipoic acid has a peak plasma value of approximately 0.56 hrs (~30 minutes) [5], my thought is that a pulsatile usage with food might be best.

I think some of the longevity studies in mice, which find no benefit to Lipoic Acid [4], suffer from the problem that lipoic acid is constantly being given as a percentage of water intake and not taken in a circadian rhythmic fashion. I'm not 100% sure on this issue yet.


1. Butler JA, Hagen TM, Moreau R. Lipoic acid improves hypertriglyceridemia by stimulating triacylglycerol clearance and downregulating liver triacylglycerol secretion. Arch Biochem Biophys. 2009;485(1):63-71.

2. Findlay, J., Hamilton, D., & Ashford, M. (2015). BACE1 activity impairs neuronal glucose oxidation: rescue by beta-hydroxybutyrate and lipoic acid.Frontiers In Cellular Neuroscience, 9. doi:10.3389/fncel.2015.00382

3. Lee CK, e. (2004). The impact of alpha-lipoic acid, coenzyme Q10 and caloric restriction on life span and gene expression patterns in mice. - PubMed - NCBI . 

4. Pashaj A, e. (2016). α-Lipoic acid as a triglyceride-lowering nutraceutical. - PubMed - NCBI . Ncbi.nlm.nih.gov. Retrieved 25 January 2016, from http://www.ncbi.nlm.nih.gov/pubmed/26235242

5. Teichert, J., Hermann, R., Ruus, P., & Preiss, R. (2003). Plasma Kinetics, Metabolism, and Urinary Excretion of Alpha-Lipoic Acid following Oral Administration in Healthy Volunteers.The Journal Of Clinical Pharmacology,43(11), 1257-1267. doi:10.1177/0091270003258654

Good call, I would agree that it's best served with food (containing carbohydrates?) I invested in some rather expensive Thorne Na-R-ALA a few years back and found it gave me a blood sugar crash when taken on an empty stomach post-workout (fasted for 16+hrs on a VLC diet.) I've since dialed back and stuck with the plain racemic mix. (Lately, I'm finding this to be an interesting stack.) This was a good article on ALA timing:

http://suppversity.blogspot.com/2014/10 ... -acid.html

Taking alpha lipoic acid before a workout to increase AMPK and hope for increases in fatty acid oxidation is only going to increase your risk of going hypoglycemic (with all its recently discussed potentially obesogenic negative side effects). Similar effects can be expected if you've been fasting, then pop a couple of ALA pills and wait another 1-2h before you're finally giving your body what it will be craving for: sugar. You think that's just biased bullshit? Well, take a parting look at the data in figure 3. Do you really want to be that normoglycemic guy who ends up in acute hypoglycemia because ALA increased his cellular glucose uptake and inhibited gluconeogenesis, i.e. the production of glucose from fat and/or amino acids in the liver, to an extend that left him hypo? I don't think so.

[Surfrank57]

Apod, almost like I am following you, lol, but have to agree with your stack choice again. This time I highly recommend to any patient undergoing a mold, fungus, or metal detox. The reasoning is not so obvious, but is highly beneficial when clearing toxins. Just like the other stack PepZin which most people would not use on a cutting diet......tricks of the trade, but they work. Way more than just n=1, by the way with these.

F

[TheBrain]

Apod, almost like I am following you, lol, but have to agree with your stack choice again. This time I highly recommend to any patient undergoing a mold, fungus, or metal detox. The reasoning is not so obvious, but is highly beneficial when clearing toxins. Just like the other stack PepZin which most people would not use on a cutting diet......tricks of the trade, but they work. Way more than just n=1, by the way with these.

Surfrank, I need some clarification. What do you mean by "stack choice"? And are you saying you recommend lipoic acid only under the conditions of mold, fungus, or metal detox? I do gather that you agree with apod that lipoic acid should be taken with food.

I'm on hold with my insurance company, and I haven't eaten yet. And I'm starving. So perhaps I'm not as sharp as usual.

[aphorist]

Taking alpha lipoic acid before a workout to increase AMPK and hope for increases in fatty acid oxidation is only going to increase your risk of going hypoglycemic (with all its recently discussed potentially obesogenic negative side effects).

While it may increase AMPK, I'm not so sure that Lipoic Acid actually increases fatty acid oxidation. It seems to prevent it really and act more like insulin, which inhibits lipolysis.

The Lee study shows the enzyme behavior under Lipoic Acid. For example, Carnitine O-palmitoyl transferase I (CPT-1) seems to be inhibited (21%), while calorie restriction upregulates it (46%). I think Lipoic Acid would be a negative for fatty acid oxidation, hence why it should not be taken away from meals, because it is not catabolic in nature but anabolic like insulin.

[Stavia]

This is above my paygrade. I thought I was meant to take it to help my mitochondria in some way that I've forgotten. So I thought morning was best.
Help???
Someone please use small words?