The Wholesome Sugar Substitute You’ve Possible By no means Heard About

This text was beforehand printed February 4, 2019, and has been up to date with new data.

As you in all probability know, irritation and oxidative harm are major drivers of most continual illnesses. What you might not be conscious of is the significance of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and NADPH oxidase, usually abbreviated as NOX, in these processes.

In a latest paper,1James DiNicolantonio, who co-wrote my guide, “Superfuel,” particulars the significance of collagen and glycine for the inhibition of NADPH breakdown. DiNicolantonio, additionally co-wrote a guide with Jason Fung, referred to as “The Longevity Resolution,” which takes a deep dive into how collagen and glycine might assist promote longevity.

The Longevity Solution

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With out enough quantities of NADPH, your physique can’t recharge glutathione as soon as it turns into oxidized. As you realize, glutathione is essential for detoxing, and each collagen and glycine successfully raises your NADPH degree by inhibiting the enzyme that breaks down NADPH.

Contemplating the significance of NADPH for optimum well being and continual illness prevention, that is actually essential data that would make a giant distinction for a lot of, as collagen and glycine are each simply obtainable and comparatively cheap. However earlier than we delve into the specifics of how glycine impacts NOX and NADPH, let’s assessment among the fundamentals.

What Is NADPH and NOX?

NADPH is the lowered type of NADP+. It is a lowering agent needed for anabolic reactions, together with lipid and nucleic acid synthesis. NOX is an enzyme complicated that’s certain to the mobile membrane, going through the extracellular area. Inhibiting NOX is a helpful technique to extend NADPH and your cells’ capability to counter oxidative stress.

NOX is activated in numerous pathological situations that generate quite a lot of oxidative stress. In actual fact, in keeping with DiNicolantonio, NOX overactivity seems to play a major position in a variety of well being situations, together with however not restricted to:

Vascular illnesses and vascular problems of different illnesses (diabetes, kidney failure, blindness and coronary heart illness for instance)

Insulin resistance

Neurodegenerative problems equivalent to Alzheimer’s and Parkinson’s

Most cancers


Pulmonary fibrosis

Erectile dysfunction

As defined by DiNicolantonio in a paper2 detailing bilirubin’s capability to inhibit NOX complexes and downregulate NOX exercise, and the advantages of spirulina for this function:

“Activation of NADPH oxidase [NOX] is a key mediator of proinflammatory microglial activation … Oxidative stress in adipocytes, stemming largely from NADPH oxidase exercise, seems to play a key position within the induction of insulin resistance and the skewing of adipokine and cytokine manufacturing in hypertrophied adipocytes.”

Six Methods to Inhibit NOX and Enhance NADPH

NADPH is used as a reductive reservoir of electrons for antioxidants that turn into oxidized and nonfunctional. NADPH can be essential to make your steroid hormones and fat. When you might have low ranges, you might be in serious trouble.

That stated, NADPH seems to be a organic molecule that may be useful or dangerous relying on how a lot of it’s circulating on the time, so it must be rigorously regulated by your physique. For instance, though NOX lowers NADPH, it additionally performs an essential position in serving to your immune system battle micro organism, and helps your T-cells to operate correctly.

It follows then, that stopping many continual illnesses would require discovering a way of inhibiting or modulating NOX. The excellent news is there are a number of methods of doing this which might be neither expensive nor cumbersome, together with the next:

Niacinamide — Taking nicotinamide can even assist enhance your NADPH degree.3

Reducing your glucose degree and avoiding fructose — Extra glucose is transformed to fructose and lowers your NAD+,4 so preserving your glucose low and avoiding fructose is a part of the equation.

Dietary ketosis — Ketone metabolism will increase the damaging redox potential of your loved ones of NAD coenzyme redox molecules, which helps management oxidative harm by rising NADPH and selling transcription of enzymes of the antioxidant pathways although activation of FOXO3a.5

Glycine and collagen — As detailed within the featured paper, glycine and collagen (which additionally accommodates glycine) even have NOX-inhibiting results, thereby elevating your NADPH degree.

The best way glycine inhibits NOX superoxide manufacturing is by bringing chloride into the cell, which reduces the cell’s capability to push out chloride ions (because it’s pushing in opposition to the next chloride gradient). Chloride ions are required to herald electrons to generate superoxide, so by minimizing chloride ions, glycine helps reduce oxidative stress.

Glycine Upregulates NADPH and Has Anticancer Exercise

Based on the featured paper,6 supplemental glycine could also be helpful for the “prevention and management of atherosclerosis, coronary heart failure, angiogenesis related to most cancers or retinal problems and a spread of inflammation-driven syndromes, together with metabolic syndrome.” Glycine can also be a superb complement to spirulina, as each suppress NOX.

The featured paper additionally particulars the anti-angiogenic exercise of glycine, which refers to its capability to inhibit the expansion of blood vessels that feed tumors. Animal research, for instance, have proven mice with most cancers which might be fed glycine exhibit suppressed angiogenesis and tumor progress, despite the fact that glycine doesn’t have an effect on the proliferation of most cancers cells straight.

DiNicolantonio and his staff hypothesize that one of many causes for this antitumor impact has to do with the truth that glycine will increase the chloride degree in endothelial cells, thereby limiting the export of chloride from the endosome. This in flip inhibits activation of NOX, which has pro-angiogenic exercise (which means it promotes the expansion of blood vessels to tumors). Based on this paper:7

“This may clarify the well-documented anti-angiogenic results of boosting plasma glycine to the excessive physiological vary. The chance that supplemental glycine might have medical utility as an anti-angiogenic agent for most cancers management deserves analysis — albeit the concurrent results of glycine on anticancer immune surveillance ought to be thought-about.

The anti-angiogenic results of glycine may also discover utility in prevention or remedy of the choroidal neovascularization related to diabetic retinopathy and age-related macular degeneration. It is going to be of curiosity to find out whether or not retinal pigment epithelium expresses glycine receptors.”

Glycine Additionally Helps Vascular Well being

NOX activation additionally performs an essential position in coronary heart illness, and by inhibiting NOX (which raises NADPH), glycine can also provide safety in opposition to cardiovascular issues. DiNicolantonio and his staff clarify:

“The position of [NOX] complicated activation in selling pro-inflammatory habits of vascular endothelium is properly documented; specifically, endothelial [NOX] performs a mediating position in atherogenesis. It’s affordable to postulate {that a} excessive proportion of this [NOX] activation happens in endosomes, and is inclined to modulation by cytosolic chloride degree.

If that’s the case, then we may anticipate elevated plasma glycine, by way of stimulation of glycine-activated chloride channels, to suppress endothelial irritation by opposing endosomal [NOX] exercise. Furthermore, the hyperpolarizing affect of glycine on endothelium may also promote vascular well being by boosting calcium inflow into endothelial cells, thereby enhancing the protecting exercise of the endothelial nitric oxide synthase.

It additionally appears not unlikely, given the documented affect of glycine on macrophages, that supplemental glycine may oppose atherogenesis and plaque instability by way of anti-inflammatory results on intimal macrophages and foam cells … Glycine can also present antioxidant safety to coronary heart muscle … Furthermore, in mice subjected to cardiac stress overload or angiotensin II administration, glycine supplementation lessens the following cardiac hypertrophy.”

Glycine Supplementation Could Enhance Your Well being

Contemplating how essential it’s to attenuate irritation and oxidative stress, and the position NOX and NADPH play in these processes, glycine supplementation holds nice promise as a easy and cheap assist. I personally take one-quarter teaspoon (about 1 gram) twice a day.

Since glycine is mildly candy, you could possibly even use it as a wholesome sugar substitute in tea or espresso. As famous by DiNicolantonio, “Intakes as excessive as 31 grams day by day have proved protected. It’s due to this fact best for incorporation into practical meals and drinks.” The paper additionally cites quite a lot of research displaying glycine supplementation could also be useful for the prevention and/or remedy of:8

  • Metabolic syndrome — As famous in DiNicolantonio’s paper, “In people with metabolic syndrome supplemented with 15 grams glycine per day (5 grams thrice day by day), plasma markers of oxidative stress declined by 25 % relative to placebo”
  • Problems from diabetes
  • Alcoholic and nonalcoholic liver problems
  • Cardiac hypertrophy

Glycine supplementation can also:9

Assist enhance sleep

Keep cartilage integrity

Reasonable the adversarial metabolic results of high-fructose eating regimen

Enhance glutathione synthesis, particularly when utilized in mixture with a N-acetylcysteine (NAC) complement

Enhance oxidant-scavenging exercise by changing to pyruvate, which is a direct scavenger of hydrogen peroxide and inhibits formation of age-advanced glycation end-products

Have antioxidant results by rising synthesis of heme and bilirubin, though proof of that is nonetheless missing, and the impact is prone to be modest

Assist detoxify glyphosate — Glyphosate is an analog of the amino acid glycine.10 It attaches in locations the place you want glycine. Importantly, glycine is used up within the detoxing course of, therefore many people would not have sufficient glycine for environment friendly detoxing.

To eradicate glyphosate, you should saturate your physique with glycine. Dr. Dietrich Klinghardt, who’s a specialist in metallic toxicity and its connection to continual infections, recommends taking 1 teaspoon (4 grams) of glycine powder twice a day for just a few weeks after which reducing the dose to one-fourth teaspoon (1 gram) twice a day. This forces the glyphosate out of your system, permitting it to be eradicated by way of your urine

Whereas glycine powder is an affordable possibility, collagen is one other various that’s extraordinarily wealthy in glycine. If going this route, I like to recommend on the lookout for natural grass fed collagen.

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