Maximizing Arachidonic Acid delivery to skeletal muscle

[neuron]

I made a cursory glance into the X-Factor thread and I didn't see any suggestion on when to take X-Factor, or other Arachidonic acid products, so here is my suggestion.

Background
After ingestion, fatty acids like arachidonic acid are emulsifed and taken up into enterocytes where they are esterfied on a glycerol backbone to form a triglyceride. Next, the triglycerides and cholesterol esters are bound together to form a chylomicron. This entity can now diffuse into the lymphatics and then into the blood. Once in the blood, the chylomicrons are free to interact with various tissue receptors depending on energy homeostasis. When needed, they can interact with an enzyme called Lipoprotein Lipase (LPL) that will hydrolyze the triglycerides back into fatty acids to be used as fuel or for storage purposes.

The point being...
In which tissue the fatty acids are deposited is a function of the energetic state of the organism overall. In a post-prandial, high fed, state, the dominant hormone is insulin. Similarly, the only isoform of LPL that is active with insulin is located on adipocytes. It should be obvious now that consuming fats when eating will direct them to adipose. This isn't necessarily a bad thing in the context of fish oil, as adipose is now recognized as a great contributer to endogenous hormone production like the prostanoids.

But...
In the context of Arachidonic Acid, the final destination should be skeletal muscle. Luckily, there is an energetic state which favors fatty acid delievery to this tissue: Exercise (or acute starvation) [1]. In an exercise-induced environment, LPL on skeletal muscle becomes active which serves as an adjunct to glycolysis for the TCA cycle via beta-oxidation. Similarly, the enzyme DGAT also becomes active in skeletal muscle which functions to store excess fatty acids as triglycerides. Since both of these enzymes are heavily active during exercise, it is clear that an excess of fatty acids are being removed from blood plasma into skeletal muscle as a reservoir (this also serves to decrease insulin insensitivity [2]).

Based on these observations
To maximize ArA supplemention it is advisable to supplement 30-40 minutes prior to exercise in order to ensure plasma delievery of ArA and also to reduce exercises effects on gastric motility.

[1] http://ajpendo.physiology.org/cgi/co...act/268/2/E229
[2] http://ajpendo.physiology.org/cgi/co...act/294/5/E882
For fulltext articles, PM genegnome

-neuron
Athletic Edge Nutrition

[Adjusting]

Great post. I always noticed best results from X-factor when I took at least 2 pills (500mg) preworkout.

[neuron]

Great post. I always noticed best results from X-factor when I took at least 2 pills (500mg) preworkout.

^Science theory in action

Luckily, I have only supplemented with ArA in this fashion - which may explain the spectrum of responders vs. non-responders.

Does anyone have info from the Baylor study as to how they dosed?

[GeneGnomeX]

Does anyone have info from the Baylor study as to how they dosed?

No strict dosing regimens:

In a double-blind fashion, subjects ingested four 250 mg
capsules containing a corn oil placebo or AA (X-Factor,
Molecular Nutrition, Jupiter, FL) over 50 days following
baseline testing.

[neuron]

No strict dosing regimens:

Too bad.

[chasinSKURT]

(or acute starvation) [1]

-neuron
Athletic Edge Nutrition

Great post

Certain supplements mimic caloric restricted diets; resveratrol, oxaloacetic acid, etc. In your opinion, is there any chance that they 'might' be able to increase efficacy of Ara?

[Andrew732]

I made a cursory glance into the X-Factor thread and I didn't see any suggestion on when to take X-Factor, or other Arachidonic acid products, so here is my suggestion.

Background
After ingestion, fatty acids like arachidonic acid are emulsifed and taken up into enterocytes where they are esterfied on a glycerol backbone to form a triglyceride. Next, the triglycerides and cholesterol esters are bound together to form a chylomicron. This entity can now diffuse into the lymphatics and then into the blood. Once in the blood, the chylomicrons are free to interact with various tissue receptors depending on energy homeostasis. When needed, they can interact with an enzyme called Lipoprotein Lipase (LPL) that will hydrolyze the triglycerides back into fatty acids to be used as fuel or for storage purposes.

The point being...
In which tissue the fatty acids are deposited is a function of the energetic state of the organism overall. In a post-prandial, high fed, state, the dominant hormone is insulin. Similarly, the only isoform of LPL that is active with insulin is located on adipocytes. It should be obvious now that consuming fats when eating will direct them to adipose. This isn't necessarily a bad thing in the context of fish oil, as adipose is now recognized as a great contributer to endogenous hormone production like the prostanoids.

But...
In the context of Arachidonic Acid, the final destination should be skeletal muscle. Luckily, there is an energetic state which favors fatty acid delievery to this tissue: Exercise (or acute starvation) [1]. In an exercise-induced environment, LPL on skeletal muscle becomes active which serves as an adjunct to glycolysis for the TCA cycle via beta-oxidation. Similarly, the enzyme DGAT also becomes active in skeletal muscle which functions to store excess fatty acids as triglycerides. Since both of these enzymes are heavily active during exercise, it is clear that an excess of fatty acids are being removed from blood plasma into skeletal muscle as a reservoir (this also serves to decrease insulin insensitivity [2]).

Based on these observations
To maximize ArA supplemention it is advisable to supplement 30-40 minutes prior to exercise in order to ensure plasma delievery of ArA and also to reduce exercises effects on gastric motility.

[1] http://ajpendo.physiology.org/cgi/co...act/268/2/E229
[2] http://ajpendo.physiology.org/cgi/co...act/294/5/E882
For fulltext articles, PM genegnome

-neuron
Athletic Edge Nutrition

AGREE 100%, I recommend the same with icarrin although it is not a fatty acid LOL.

[GeneGnomeX]

Great post

Certain supplements mimic caloric restricted diets; resveratrol, oxaloacetic acid, etc. In your opinion, is there any chance that they 'might' be able to increase efficacy of Ara?

I'm not neuron but,

I can only find this study which shows a doubling of LPL expression in skeletal muscle after a 20h fast. I am not aware of any resveratrol studies showing a change in LPL in skeletal muscle but not other tissues, but in theory it should.

IMO resveratrol is far from a calorie restriction mimetic yet; some of the earlier studies haven't been able to be replicated. Resveratrol hasn't been subjected to rigorous study like calorie restriction.

Regardless, even if they would result in a favorable partitioning, the healthspan and maximal lifespan increasing effects of dietary restriction are seem to be at least partly mediated by a reduction in the anabolic pathway (PI3k->mTOR and all in between and downstream); I would be curious to see if they could still be achieved with mTOR overexpression or REDD2 knockout (or myostatin) in only the skeletal muscle. It seems it isn't possible to get the best of both worlds of maximizing muscle mass and mimicking energy restriction.

[DR_P]

great read, neuron, but even when Ara is ingested with meals and mostly directed towards adipose tissue, don't forget that adipose tissue (especially VAT) has a high flux and - depending on the energetic demands - does release fatty acids with the purpose to be utilised by muscles.
moreoever, don't forget that fatty acid oxidation is the predominant way of energy delivery during resting state. so, muscles will most of the time be receptive to Ara.

so, even when ingested wthout strict intake scheme, Ara may be well available to muscle tissue

[neuron]

so, even when ingested wthout strict intake scheme, Ara may be well available to muscle tissue

The problem is, the route from adipose tissue to skeletal muscle is not a simple function of adipose 'releasing' the FAs into the blood stream. FAs are not soluble and have to be coupled with lipoproteins for plasma transport (an energetic process). Furthermore, skeletal muscle will be competing with other tissue for them, and typically relys on its own store of triacyglycerides for beta-oxidation (at rest).

Ultimately, you would not be getting close to the same concentration of ArA from adipose than when channeling it directly to skeletal muscle. This is no small idea, because ArA seems to be heavily dose-dependent. A slow yield of ArA from adipose is unlikely to perfom the same as a high-dose (Llewellyn mentions 1g, but I've found 2g to be the best).

[AndItStonedMe]

I just started supplementing ArA a couple of days ago. I'll start taking it all pre-workout, instead of multiple doses throughout the day, and see how it goes.

[Trans_Isomer]

Good read Neuron,

What gains have you typically noticed yourself? Some points im interested in:

-total weight gain
-bf% drop (if you measured it)
-strength increases on major lifts
-mood changes
-any headaches?

[_Smitty_]

great post, neuron!

[Illadelphia]

We've seen alot of dosing pattens go:

1 in the am

1 around noon

2 pre-wo

[neuron]

Good read Neuron,

What gains have you typically noticed yourself? Some points im interested in:

-total weight gain
-bf% drop (if you measured it)
-strength increases on major lifts
-mood changes
-any headaches?

1) Negligable
I'm not discounting this as a potential characteristic of ArA, but just that in my experience, a leaning effect seems to predominate. The addition of an anabolic agent may tip the scale, however.
2) Noticable, but without being measured, it's hard to guestimate % drop.
3) Strength goes up
It's interesting that theory suggests that ArA would be anabolic via myonuclear addition, yet no study has replicated this in humans. Similarily, there is no established mechanism for strength gain from ArA, yet this is what I find most observable, and it was also seen somewhat in the baylor study (1 rpm).
4) No mood changes.
5) Yes. Joint issues were also a minor nuisance, although I also double-dose.

[GeneGnomeX]

Similarily, there is no established mechanism for strength gain from ArA, yet this is what I find most observable, and it was also seen somewhat in the baylor study (1 rpm).

I don't think this study can tell us much of anything. Here are a few reasons.

1. The participants trained on their own (prescribed regimen) for the 50 days (which is good for real world relevance but there is likely a great fluctuation in training intensities- the number of subjects in each group was low)
2. Subjects had to ensure themselves they consumed an extra 500kcal/day and reach 2g/kg protein per day. The dietary differences suggest this did not go well.

So not looking at mathematical significance, here are the hard averaged numbers:


So in the 1RM bench which is heavily advertised by MN, a measly 6 pounds great in the AA group over 50 days with 15 and 16 subjects in each group. And in the AA group, starting strength was lower on average in the tests, so it may have been easier to increase during the study. Also consider the following:

Here are the dietary differences:



As you can see the AA group consumed more across the board of total calories and each macronutrient.

Look again in the first table. The AA group gained more total body mass but the difference is in the fat mass gain.

Drop the calories to make them even in both groups and I wonder if the 1RM bench would still be greater in the AA group.

[Robboe]

Does anyone have info from the Baylor study as to how they dosed?

http://www.pubmedcentral.nih.gov/art...medid=18045476

[UNCnate]

FWIW, I have used X-Factor several times. 2 or 3 times, Im not sure. None in the past 2-3 years. I developed some stomach issues and I am hesitant to use it. Nonetheless, the first time I used X-Factor I did 4 doses spread out through the day, the other times I did 2 doses of 2 pills, 1 serving in the morning, 1 45 minutes preWO. Anecdotally, the 2/2 seemed to work better for me.

[Mfusick]

Thanks - interesting thread. Subsribed

[Free Weight Friedel]

We've seen alot of dosing pattens go:

1 in the am

1 around noon

2 pre-wo

That's what I'm doing right now.

But, Neuron, are you saying it would be more beneficial to take all 4 caps pre-workout?

[neuron]

That's what I'm doing right now.

But, Neuron, are you saying it would be more beneficial to take all 4 caps pre-workout?

Taking all 4 would ensure the greatest % of ArA delivery to skeletal muscle. You could also take them 60-90 min. after eating the in post-absorptive state when insulin is far less active.

[Adjusting]

But, Neuron, are you saying it would be more beneficial to take all 4 caps pre-workout?

I can already imagine the kind of headache I would get from that.

[1MoreRepUFool]

Taking all 4 would ensure the greatest % of ArA delivery to skeletal muscle. You could also take them 60-90 min. after eating the in post-absorptive state when insulin is far less active.

So an empty stomach is better to take than with food?

Would 2 in morning on empty stomach and 2 before a workout make sense?

Or 4 before workout?

or 1 cap 4 times a day ?

[AndItStonedMe]

I can already imagine the kind of headache I would get from that.

I just started taking it full dose all at once, but I haven't had any headaches. It's straight ArA though, not sure if you're talking about the ArA causing headaches or other things that might be in a prop blend causing headaches.

[Adjusting]

I just started taking it full dose all at once, but I haven't had any headaches. It's straight ArA though, not sure if you're talking about the ArA causing headaches or other things that might be in a prop blend causing headaches.

I'm talking about Ara headaches. I believe this is due to iNOS increases - Neuron would know more specifically about what causes Ara headaches.

I'm very susceptible to headaches from X Factor. Sometimes I would use XF like this: 1 cap in the morning, 2 caps preWO and 1 cap PWO - this gave me the best results but the headaches would get real bad. To the point where I needed an Advil to sleep and as we know, an Advil isn't the smartest thing to use when on XFactor. So I couldn't always use XF like this.

[neuron]

I'm talking about Ara headaches.

Have you tried asprin?

Asprin has about 10x less affinity for COX-2 vs. COX-1.

A low dose asprin might blunt the effects of the headache enough to support its continued supplementation in this manner.

[neuron]

So an empty stomach is better to take than with food?

Would 2 in morning on empty stomach and 2 before a workout make sense?

Or 4 before workout?

or 1 cap 4 times a day ?

You could take them on an empty stomach spread throughout the day (although I question the reasoning behind this approach) or take all 4 prior to workout to maximize its benefits.

You should certainly play around with the dosing to minimize any possible negative side-effects, although the new X-Factor contains ingredients to limit leukotriene production.

As an aside - I just received a bottle of the new X-Factor and will be watching for any possible side-effects (joint issues, headaches, exc).

[1MoreRepUFool]

You could take them on an empty stomach spread throughout the day (although I question the reasoning behind this approach) or take all 4 prior to workout to maximize its benefits.

You should certainly play around with the dosing to minimize any possible negative side-effects, although the new X-Factor contains ingredients to limit leukotriene production.

As an aside - I just received a bottle of the new X-Factor and will be watching for any possible side-effects (joint issues, headaches, exc).

I am on my second bottle of advanced. First bottle I used normal and switch to advanced for the second bottle. I don't get headhaches (I do but I can live with it) that would keep me from taking the most effective way possible.

Ok- so your saying take it when the muscles are hungry to absorb like before workout. I will try to take pre workout and report back.

I had been taking 4 times a day- 1 cap at a time.

[Mfusick]

Have you tried asprin?

Asprin has about 10x less affinity for COX-2 vs. COX-1.

A low dose asprin might blunt the effects of the headache enough to support its continued supplementation in this manner.

So your saying that asprin is ok to take for headache on xfactor. Or is the best choice if you have to take somthing?

[neuron]

Or is the best choice if you have to take somthing?

Exactly. IF you have to take something, then you should choose (baby) asprin vs. ibuprofren or another NSAID.

Ibuprofren has a much higher affinity for COX-2 - which is also why it is ascribed less gastric issues. COX-1 is responsible for decreasing gastrin secretion (i.e. less COX-1=more HCl).