A Creatine Pill You Can FEEL

Creatine Hydrochloride – 2,000 mg

The Inspired Nutraceuticals CR3 Ingredients – Four capsules, four ingredients, all kinds of creatine-driving synergy

Creatine is the most well-researched sports supplement ingredient, with numerous research studies demonstrating incredible benefits in terms of power,^[1,2]weight gain,^[2]lean mass,^[2-6]sprint speed,^[7-9]hydration,^[10]fatigue reduction,^[11-14] and even overall well-being^[15-17] and improved cognition (for vegetarians)^[18,19] in various forms of creatine. We’ve even seen slight improvements to testosterone^[20-24] and bone mineral density^[5] – especially for those who don’t eat meat.

Many of the studies cited here aren’t one-offs either, several are meta-analyses, consistently confirming that this is a great dietary supplement for nearly anyone.

The questions are, what type of creatine, and how much?

Inspired Nutraceuticals takes an interesting approach here, because it’s not the standard “3-5 grams of creatine monohydrate” that is normally recommended. We’ll dig in to their decision, but first, let’s briefly discuss how creatine works:

What does creatine do?

Creatine may seem like a “do-it-all” performance enhancer because it has a very general function: it donates a phosphate group where it’s critically needed — for cellular energy production. The recipient of that phosphate group is the adenosine diphosphate (ADP) molecule, which combines to create adenosine triphosphate (ATP),^[25-28] our cells’ “energy token”. Realize that our cells don’t care about “calories” — they care about ATP. And creatine enables us to generate more of it, especially when we need it.

Various forms of creatine very consistently improve lean tissue mass, chest press strength, and leg press.^[3]

Low ATP levels mean low performance and energy levels. With the help of creatine, we can build more, and it yields the numerous benefits cited above. Supplementing it means that the body won’t need to generate as much of it,^[29] saving our organs time and energy to do other things they’re better equipped to do.

Creatine hydrochloride

Creatine Hydrochloride (Creatine HCl) is a “creatine salt” in which creatine is bonded to hydrochloric acid, something we see frequently in supplements. Reason being, we get incredible solubility with hydrochloride salts in water, and that’s indeed the effect with Creatine HCl compared to monohydrate.^[30] Animal models have shown that it will lead to better oral absorption,^[31] but that hasn’t been demonstrated in humans.

Ultimately, creatine hydrochloride is a good molecule — especially in capsule-based products due to its acidic taste — but our take is ultimately that we don’t care what kind of creatine supplement you use, just get it in every day.

So now let’s talk about dosage, but to do that, we have to talk about sources and excretion:

How do we get creatine naturally?

The next question is, where does creatine come from naturally? Because if we eat a lot, we theoretically don’t need to supplement as much, which is the case.

Creatine is found most heavily in beef, with roughly 2-2.5 grams per pound of uncooked meat.^[32,33] Chicken has a bit less, with 1.5 grams per pound.^[34]

How much creatine do we need?

In general, the average male excretes two grams of creatine per day^[35] – but this ultimately depends on your size and amount of muscle mass. Men lose between 1.6-1.7% of their creatine per day,^[36,37] while women lose a touch less.^[35]

More of this means less creatine needed to supplement. Image courtesy The Provision House

This leads us to believe that creatine should be an essential “vitamin” – we need to maintain saturation, otherwise we cannot perform or even think at our peak.

With the above data, we can fine tune our dosing strategy. Do we need five grams per day once we’re saturated with creatine? Not if we eat enough meat, and not if we take an amplified, bioavailable form.

It turns out that this is exactly what we’re getting with Inspired Nutraceuticals CR3 — two grams a day, to cover our “expenditure” on top of whatever meat we’re eating (and we do recommend meat-heavy diets) — but with absorption amplification due to our next ingredient:

AstraGin (Astragalus membranaceus and Panax notoginseng) (root) – 50 mg

AstraGin is a combination of Astragalus and Panax Notoginseng that’s been shown to increase ingredient absorption, especially of amino acids!

The first of two novel ingredients from NuLiv Science is AstraGin, a natural absorption-booster that’s made from Astragalus membranaceus and panax notoginseng.

AstraGin works by enhancing the body’s ability to absorb nutrients and compounds through the intestinal walls. The mechanism is described below, but the important part is that AstraGin has been demonstrated to enhance creatine absorption by up 33% and agmatine absorption by 36%!^[38] We haven’t yet discussed agmatine, but it’s the next ingredient.

This theoretically makes our two grams of creatine hydrochloride the equivalent of a 2.66 gram dose, allowing our bodies to absorb more and get it back into the muscle tissue to reach saturation. Should you still eat meat? Always! And if you do, do you need to worry about loading monstrous amounts of creatine? We don’t think so.

How does AstraGin work? Transporter upregulation

AstraGin’s mechanism revolves around upregulation of mRNA and three key transporters involved in nutrient uptake:^[38]

AstraGin amplifies tons of ingredients, but we rarely talk about how it boosts absorption of creatine!^[38]

1. Sodium-glucose cotransport 1 (SLGT1) controls the sodium-dependent glucose uptake across cells.
2. Glucose transporter type 4 (GLUT4) is a primary glucose transporter that helps keep normal glucose levels.
3. Cationic amino acid transporter 1 (CAT1) moves amino acids throughout the body.^[38]

More ATP Production

NuLiv Science’s research shows that AstraGin can increase ATP production in HepG2 liver cells by 18%, even without creatine involvement!^[38] This is a statistic few discuss, and is ultimately the entire goal of creatine in the first place, making for an even more synergistic placement in CR3.

Added gut health improvements

AstraGin also helps with general gut health through this upregulation. NuLiv Science’s research has shown that it can lower inflammation in the intestinal wall by 73% in animal research.^[38]

Synergy with Senactiv

Increase the absorption and effectiveness of your supplements with AstraGin from NuLiv Science!

Further, we speculate that there is some incredible synergy between AstraGin and Senactiv, as discussed in our article titled Astragalosides and Ginsenosides: Differentiating NuLiv Science’s Ingredients. Senactiv is also included in CR3 and is detailed below.

Why isn’t AstraGin in more creatine supplements?!

We’ve seen AstraGin work wonders, but we often only see it in pre workouts and amino acid supplements. While it also has great benefits in those categories, it seems to be forgotten when it comes to creatine absorption or ATP enhancement!

But Chris Waldrum and his team at Inspired Nutraceuticals didn’t skimp, and when it comes to creatine pills, it’s always worth making room for 50 milligrams of AstraGin.

Agmatine Sulfate (AgmaMax) – 750 mg

Now it’s time to get a little bit of a pump and nitric oxide boost to drive even more nutrient delivery, and what we love is that it comes from an ingredient that’s not in too many pre workout supplements lately.

Agmatine is simply decarboxylated arginine, but research suggests it may be far better!

We’re talking about agmatine sulfate, which is a metabolite of the well-known amino acid L-arginine. Agmatine is an arginase inhibitor, meaning that it will prevent the breakdown of arginine, as it inhibits the arginase enzyme from doing that job.^[39] We often call this a “defensive” nitric oxide booster – we always get plenty of “offensive” plays in pre workouts such as the DVST8 series, but agmatine enables us to prolong those effects to keep NO around longer, and stacks very well in capsules.

However, there is some offensive action with agmatine as well – additional research has shown that it also boosts nitric oxide synthase, which is the enzyme that helps generate nitric oxide.^[40] This leads us to a dual-pronged approach.

And as we saw above, AstraGin can help increase agmatine absorption by 36%, so you can consider this roughly equivalent to about a gram of “non-amplified” agmatine — which is right where we like to dose it pre workout anyway!

More nitric oxide, more blood flow

On top of its creatine boosting abilities, agmatine can enhance agmatine’s absorption as well.^[38]

With improved nitric oxide levels, we will get a vasodilation effect that expands our blood vessels, improving blood flow and ultimately nutrient delivery.

Finally, we may even feel a slight focus boost from agmatine, as it has a few neuromodulatory properties and functions as a neurotransmitter!^[41] While it’s not the most powerful nootropic, it’s an ingredient that can be felt one way or the other, most often with its increase in pumps.

But finally, the ingredient we’ve really been feeling lately, Senactiv:

Senactiv (Panax notoginseng (root) and Rosa roxburghii (fruit)) – 50 mg

The second of our two novel NuLiv Science ingredients, Senactiv is an ingredient we’ve recently really come to love, given its endurance-boosting properties that we can anecdotally feel considerably well. It’s made from different portions of Panax notoginseng than AstraGin, as well as Rosa roxburghii, with the research taking a different direction – mainly towards endurance and VO2max support.

A senolytic ingredient

Out with the old, in with the new. Regenerate senescent cells and improve performance with NuLiv Science’s Senactiv

Senactiv is a senolytic supplement, which means that it’s a compound that can help the body replace old, deteriorating cells (also known as senescent cells) by inducing and expedited healthy death and clearance of those less useful cells.^[42] This encourages new cell generation and promotes growth and overall health — exactly what we want when taking creatine and generally trying to grow. This may sound a bit alarming, but it’s a natural process and Senactiv just pushes it through faster, enabling for more growth.

In addition, this process occurs in the endothelial lining of skeletal muscle cells, so it’s a perfect mechanism for a creatine / muscle building supplement.

NuLiv Science’s research on the ginsenosides in ginseng have been very fruitful with respect to this. A placebo-controlled study showed that prior to exercise, muscle tissue that was exposed to Senactiv’s ginseng extract had enhanced glycogen replenishment and diminished inflammation (via markers) compared to placebo.^[43]

A boost in VO2max: something creatine doesn’t reliably do

Atop those anti-inflammatory properties, Senactiv’s ginseng fraction boosted VO2 max by 20% versus placebo.^[43] This is fantastic to see in a creatine supplement, because it’s one of the few things that creatine doesn’t reliably do! Creatine may help with repeat-bout sprint efforts, but it’s not huge in the endurance world.

Under the hood, biopsies of muscle tissue show that the ginseng extract in Senactiv can lead to 47% more citrate synthase,^[43] critical to the ATP production pathway. This yields even better synergy with creatine and AstraGin! Additional research shows improvements for free radical damage, inflammation, lipid peroxidation, and muscle damage markers.^[43-46]

Senactiv: Regenerate new cells faster

Improved VO2 Max from Senactiv means big things for everyone, not just endurance athletes! Image courtesy NuLiv Science.

Senactiv is meant to help you grow and recover faster by clearing out old cells and encouraging new growth.^[44] On the acute front, it can help with muscle tissue glycogen replenishment, working 2.7 times faster,^[43] so don’t feel afraid to carb up after your CR3-driven workout.

Last, research shows that Senactiv boosts the Pax-7 protein and MYf5 gene by 81%,^[47] an indication of satellite cell generation in muscles.

This may sound deep, but the point is that this is a very unique supplement for both endurance and growth, and it’s one that we’ve been feeling throughout our training. You can go on an even deeper dive in our article titled Senactiv from NuLiv Science: Regenerate Senescent Cells and Perform Better.

Further synergy with AstraGin!

Finally, we get into how this differs and synergizes with AstraGin in our article titled Astragalosides and Ginsenosides: Differentiating NuLiv Science’s Ingredients, further demonstrating how unique and powerful of a supplement CR3 is.