Arginine vs nitric oxide — which is better for men?

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Arginine vs nitric oxide — which is better for men?

Of the over-twenty protein amino acids, arginine sits near the very top in importance.

This is because arginine is absolutely essential for an effective immune system. 

Arginine can be recycled by the body, so it’s not strictly considered “essential,” but there are times the body cannot keep up with demand and arginine levels drop.

This can lead to sepsis or candidemia. Arginine levels are nearly always found low in these conditions.

Arginine has one unique and important function that makes it indispensable for the immune system, one that cannot be substituted by anything else.

Arginine is the only precursor for nitric oxide, a reactive nitrogen product created by most white blood cell types.

Nitric oxide and nitrogen dioxide are highly-damaging to bacteria and fungi.

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Although damaging to the body, these are fatal to pathogens.

This is because reactive nitrogen species are directed towards the target.

Nitric oxide and superoxide are actually focused against Candida albicans by neutrophils, so concentrations are always the highest at the yeast cell wall.

And for any collateral damage caused by stray nitric oxide, γ-tocopherol would be effective. 

Gamma-tocopherol is a vitamin E subtype that safely “traps,” or adducts with, reactive nitrogen species.

Nitric oxide and ṄO2 are also produced inside of macrophages, an immune cell type that literally engulfs pathogens.

But without having enough nitric oxide produced inside, Candida albicans will actually take-over the macrophage and escape.

So without enough killing power, the macrophage paradoxically serves to disseminate the yeast and not kill it.

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Besides superoxide (O2), the killing power of macrophages has also been shown to be dependent on the production of nitric oxide.

And this can only be made from L-arginine.

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This has been proven directly, in the lab, using a petri dish, Candida albicans, macrophages, and L-arginine.

They researchers found that Candida would proliferate by restricting L-arginine, which is almost like a model for sepsis/candidemia.

And the restriction of any other amino acid had no effect.

‘Except for L-arginine, addition of all amino acids singly or in combination, failed to restore any significant fungistatic capability.’ ―Granger

He also showed that inhibitors of iNOS — the nitric oxide-producing enzyme — greatly reduces killing power.

He also determined the concentration curve, giving us valuable information that could be used to determine dosing.

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This is important, since the maximum concentration is more than twice the concentration of what is normally found.

Average concentrations of L-arginine fall in the range of 70 to 90 μM, while those found in sepsis are around 40 to 50 μM (Davis, 2011).  

And eight hundred milliliters of L-arginine given at a concentration of 8 μM could be expected to increase the plasma L-arginine concentration by 43 μM.

This equates to a total dose of 1,148mg of L-arginine, a convenient number since this is the most commonly-sold dose: 1,000mg or 1,200mg tablets — take your pick.

About ~3000mg L-arginine should achieve maximum Candida killing power, in macrophages. 

But there are also the neutrophils, which also use L-arginine.

Neutrophils are just as important.

Right behind antibiotics and glucocorticoids in candidemia risk factors is neutropenia, or low blood neutrophil concentrations.

And glucocorticoids lower immunity, in part, by lowering ṄO.

So macrophages and neutrophils are the primary killing agents for fungi.

Natural killer cells can of course help, but these cells seem better-directed against bacteria.

It is the neutrophil that seems most important against Candida albicans.

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Neutrophils are best known for their ability to create superoxide (O2), since this effect was discovered first.

They also create hypochlorous acid (HClO) from the chloride ion (Cl), meaning that consuming salt might not be a horrible idea after all.

Neutrophils also secrete lactoferrin, an iron-binding protein.

This is for good reason, as it has been shown that iron overload causes Candida albicans to proliferate.

But neutrophils do also create nitric oxide, a reactive molecule shown every bit as important.

This is best shown by using an inhibitor of iNOS such as N-monomethyl arginine.

Adding this to the cells will lower the nitric oxide formed, and also the Candida-killing potential:

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The effect appears small, but that’s only because the culture media he used (RMPI) already has 200μM arginine.

The control value (white bar) already represents a near-maximum concentration of arginine, and the neutrophil can only form nitric oxide so fast. 

Most people have a blood arginine concentration around 75 μM.

‘…there was a close association between the spontaneous production of nitrite and the candidacidal activity of peritoneal neutrophils.’ ―Fierro

We already consume about 5 grams of L-arginine per day from food, but I would be careful about taking any more than a few more grams.

Too much arginine can cause a rash. Because nitric oxide is a gas, it’ll escape through the skin. 

Autoimmune rash conditions are always characterized by elevated nitrates.

In lupus, nitrates have been found elevated three times the normal levels in the cerebrospinal fluid.

And on the promotional material of Viagra™, which increases nitric oxide, you’ll find “rash” as the first-listed side-effect.

And reactive nitrogen species can also cause fatigue. As small, neutral, and lipophilic gases they can get into the nerves and cause anesthesia… and tyrosine adducts (i.e. nitrotyrosine).

So if you get a rash or get fatigued, it would be good to lower the dose.

Gamma-tocopherol, if taken a few days beforehand, should prevent most collateral damage.

And γ-tocopherol shouldn’t affect the Candida-killing power or arginine.

Fungi have very few lipids on their cell wall (<10%), it being mostly protein and polysaccharides, and so wouldn’t be expected to incorporate γ-tocopherol.

You might think that because a bit too much arginine can cause fatigue, the best time to take it would be during the night.

But that would be the worst time to take it because melatonin turns-off nitric oxide production, going from daytime microbe killing to nighttime repair. 

Tumor necrosis factor alpha is the most powerful cytokine regulator of nitric oxide production (via iNOS), and this has a strong circadian component.

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So it would be (1) best to use arginine in the morning, (2) up to about 3,000mg for maximum Candida-killing activity, and also (3) while taking γ-tocopherol to limit collateral damage.

And simple aspirin is also effective against Candida, a species having cyclo-oxygenase like enzymes that can be inhibited.

Candida albicans use prostaglandin E₂ as a growth factor.

It has been shown that cyco-oxgenase inhibitors, like aspirin, inhibit Candida albicans transformation and growth. 

And there are also many dietary modifications, such as eliminating grains, which can certainly help…

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