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Did you know that researchers have found a link between high levels of glutathione and better sleep? 

Specifically, it has repeatedly been found in multiple studies that people with higher levels of glutathione are better able to easily fall asleep, wake up on time, and feel refreshed in the morning

Glutathione is essential to helping the body detoxify itself while sleeping, which helps ensure its optimal function. 

In this article, we’ll be discussing how glutathione benefits melatonin and acts as a sleep aid in the body. 

However, before we do, it is important to know even more about this very important antioxidant.

What Exactly Is Glutathione?

Did you know that the body is able to make glutathione in the liver? The same cannot be said for most other antioxidants. 

Glutathione is a naturally occurring antioxidant that plays a crucial role in eliminating free radicals to reduce oxidative stress and damage in the body. It is especially helpful in preventing free radical damage to DNA.

Glutathione is a tripeptide molecule made up of three amino acids

  • Glycine
  • Cysteine
  • Glutamate, or glutamic acid

Synthesis

Glutathione biosynthesis is a complex process but, in short, there are a few key steps.

The rate-limiting enzyme glutamate-cysteine ligase links glutamate and cysteine together to form gamma-glutamylcysteineThen, the enzyme glutathione synthase, or glutathione synthetase, links gamma-glutamylcysteine and glycine together to form GSH, also known as reduced glutathione or L-glutathione.

Let’s take a closer look at the amino acids that make up glutathione.

Glycine

Glycine is also a neurotransmitter that can both stimulate or inhibit brain and nervous system activity. Glycine helps decrease body temperature, which is important in the body’s process of preparing itself to go to sleep. One study published in Neuropsychopharmacology showed that glycine supplementation was able to decrease core body temperature and significantly decrease the amount of time it took to fall asleep

It also helps increase serotonin levelsSerotonin is another neurotransmitter that encourages deeper and more restful sleep, and is essential to the production of melatonin, the “sleep hormone.” 

Glutamate

Glutamate is a precursor for GABA (or gamma-aminobutyric acid), which is a neurotransmitter that helps suppress neuronal activity, and increase calming alpha waves to help you fall asleep faster and more deeply.

Cysteine

Cysteine helps suppress the brain’s synthesis of glutamate and promote its conversion to GABA. The metabolism of cysteine yields the amino acid taurine, which has many cytoprotective effects by suppressing glutamate-induced toxicity, including protecting neurons from oxidative stress. 

Glutathione and Other Antioxidants

Did you know that glutathione interacts with other important antioxidants in the body?

Glutathione helps to regenerate, or recycle, Vitamin C and, indirectly, Vitamin E through enzymatic reactionsVitamin C and Vitamin E also serve as important antioxidants that neutralize free radicals and fight oxidative stress in the body.

Next, let’s take a look at:

What Factors Affect Glutathione Levels in the Body?

Much like with melatonin, the levels of glutathione produced by the body decline with increasing age. 

A representative study of community-dwelling elderly citizens found that higher glutathione levels correlated positively with higher levels of physical health and wellness, higher levels of self-rated health, and fewer illnesses

There are several ways to increase the levels of glutathione within the cells:

  1. Decrease the need for glutathione
  2. Provide other antioxidants
  3. Glutathione supplementation
  4. Provide specific nutrients that promote glutathione production
  5. Foods and drinks

Let’s dig a little deeper:

Decreasing the Need for Glutathione

To decrease the need for glutathione, you must decrease your toxic load. That can be done by limiting your alcohol consumption, and decreasing your exposure to persistent organic pollutants, or POPs, which primarily come from foods grown through traditional agriculture.

For reference:

The first 12 POPs described under the Stockholm Convention include:

  1. Aldrin
  2. Chlordane
  3. DDT
  4. Dieldrin
  5. Endrin
  6. Heptachlor
  7. Hexachlorobenzene (HCB)
  8. Mirex
  9. Toxaphene
  10. Polychlorinated Biphenyls (PCBs)
  11. Dioxins
  12. Polychlorinated Dibenzofurans (PCDF)

Aldrin, chlordane, DDT, dieldrin, endrin, heptachlor, mirex, and toxaphene are used as pesticides.

Dioxins and PCDF are chemical by-productsHCB and PCBs are chemical by-products, and used as industrial chemicals.

16 other chemicals were later added to the list of POPs, which include:

  1. Alpha hexachlorocyclohexane (α-HCH)
  2. Beta hexachlorocyclohexane (β-HCH)
  3. Chlordecone
  4. Decabromodiphenyl ether (deca-DBE); commercial mixture (c-decaBDE)
  5. Hexabromodiphenyl (hexa-DBE)
  6. Hexabromocyclododecane (HBCD)
  7. Hexabromodiphenyl ether (BDE-153) and heptabromodiphenyl ether (BDE-171)
  8. Hexachlorobutadiene (HCBD)
  9. Lindane
  10. Pentachlorobenzene (PeCB)
  11. Pentachlorophenol (PCP; not to be confused with the drug) and its salts and esters
  12. Perfluorooctane sulfonic acid (PFOS), its salts, and perfluorooctane sulfonyl fluoride (POSF)
  13. Polychlorinated naphthalenes (PCNs)
  14. Short-chain chlorinated paraffins (SCCPs)
  15. Technical endosulfan and its related isomers (ions or molecules with the same formula, but different atomic structures)
  16. Tetrabromodiphenyl ether (tetra-DBE) and pentabromodiphenyl ether (penta-DBE)

α-HCH, β-HCH, chlordecone, lindane, and technical endosulfan and its related isomers are used as pesticidesDeca-DBE, hexa-DBE, HBCD, BDE-153 and BDE-171, PFOS, its salts, and POSF, SCCPs, and tetra-DBE and penta-DBE are used as industrial chemicalsHCBD and PCNs are chemical by-products, and used as industrial chemicalsPeCB is a chemical by-product, and used as a pesticide and industrial chemical.

Providing Other Antioxidants

You can also increase your intracellular levels of glutathione by supplementing with other antioxidantsWhen it comes to providing other antioxidants to decrease oxidative stress, it would be a good idea to consider alpha lipoic acid, or α-lipoic acid, supplementation.  

It has been shown to increase levels of glutathione within the mitochondria, despite having no involvement in the biosynthesis or recycling processes of glutathione. Additionally, incorporating a family of antioxidants such as Vitamin C and Vitamin E is important due to their role in recycling glutathione

Glutathione Supplementation

The simplest way to increase your intracellular levels of glutathione is through glutathione supplementationGlutathione supplementation can be done orally, topically, intravenously, intranasally, or in nebulized form, which is liquid medicine turned into mist. Research studies have shown that intravenous administration, inhalation, and intranasal ingestion of glutathione have increased systemic levels of the antioxidant.

Specifically, intravenous administration has had short-term efficacy in treating several diseases. Oral and transdermal liposomal glutathione have shown great potential in increasing intracellular glutathione levels.

Let’s take a moment to look at liposomal glutathione.

Liposomal Glutathione Supplementation – In Vitro (test-tube experiments)

Liposomal glutathione has also been studied for its ability to restore levels of intracellular glutathione and provide neuroprotective effectsThis was done using an in vitro model of Parkinson’s disease using paraquat plus maneb, or PQMB in rat mesencephalic cultures.

For reference: 

Paraquat is an herbicide that is toxic to people because of its redox activity, and has been linked to the development of Parkinson’s disease. Maneb is a fungicide used to create a toxin-based animal model for Parkinson’s disease. 

Cultures of mesencephalic neurons are used to study the mechanism involved with dopaminergic cell death, which is the primary characteristic feature of the neuropathology of Parkinson’s disease. Over the course of 4 hours, both liposomal- and non-liposomal GSH were able to restore the depleted levels of intracellular glutathione back to control levels. However, the EC50 of liposomal-GSH was 4.75 μM; the EC50 of non-liposomal GSH was 533 μM

To be clear:

EC50 is a pharmacology term that describes the drug concentration that produces 50% of a maximal effect. So, the lower the E50 value, the greater the potency, because you won’t need as high a concentration to get the maximal effect. Thus, liposomal-GSH was MORE than 100 times as potent as non-liposomal GSH. Liposomal-GSH also provided dose-dependent protection against PQMB with a similar E50 value to that found for the restoration of depleted GSH. 

PQMB depleted intracellular GSH by half

Liposomal-GSH had a sparing effect on the GSH produced within the body during PQMB exposure, but did not require the biosynthesis of GSH to provide these neuroprotective effects. 

For those who don’t know:

Sparing effect means that the presence of liposomal-GSH decreased the required levels of GSH to be naturally produced within the body.

When the researchers administered liposomal-GSH at 200 times the E50 amount to restore the depleted levels of intracellular GSH, there was no toxicity observed.

The researchers of this study concluded that liposomal glutathione shows promise as a potential therapeutic treatment to help with neuronal maintenance.

Liposomal Glutathione Supplementation – In Vivo (tested on human cells)

Another study was done to investigate whether oral administration of liposomal-GSH is effective at increasing GSH levels in vivo. 

Over the course of a month, 12 healthy adults were randomly given oral liposomal-GSH at two different doses of either 500 mg daily or 1,000 mg dailyThe participants’ GSH levels in their whole blood, red blood cells, blood plasma, and peripheral blood mononuclear cells, or PBMCs, were measured before the experiment, and after 1, 2, and 4 weeks of GSH administration.

For reference:

Whole blood refers to human blood given in a standard blood donation. It consists of red blood cells, white blood cells, platelets, and blood plasma. 

PBMCs are peripheral blood cells with a round nucleus, which include lymphocytes, such as B-cells, T-cells, and NK cells, monocytes, and macrophages, all of which are essential components of the immune system.

After 1 week, GSH levels were increased. 

The maximum increases occurred after 2 weeks of administration, with more than a 40% increase in whole blood at a 500 mg/daily dose

There was about a 28% increase in red blood cells after 1 and 2 weeks at a 1,000 mg daily dose, and after 2 weeks at a 500 mg/daily dose. 

There was about a 25% increase in blood plasma after 2 weeks at a 500 mg/daily dose. The results were significant only after 2 and 4 weeks. 

There was about a 100% increase in PBMCs after 2 weeks at a 500 mg/daily dose. The results were significant only after 2 and 4 weeks, just as with the levels of GSH in blood plasma.

These findings suggest that liposomal glutathione supplementation provides the greatest benefit to subjects with the lowest baseline GSH levels. 

The increase in GSH levels across all parameters also suggests a systemic effect.

Nutrients that Promote Glutathione Production

Let’s go back to the five main methods to increase intracellular levels of glutathione.

In terms of providing specific nutrients to promote glutathione production, supplemental cysteine in the form of N-acetylcysteine, or NAC, or undenatured whey protein have proven to be effective at raising the intracellular levels of glutathione.

To be clear:

Undenatured whey protein refers to whey proteins that are processed directly from pasteurized milk, rather than from whey derived from the cheese-making process, in which whey is pasteurized twice.

With some variation, depending on the person, 1000 mg daily of N-acetylcysteine will significantly increase glutathione in just about all patients. 

The patients who don’t react well to NAC may use SAMe instead.

Also known as S-adenosylmethionine, SAMe is an essential precursor for the transsulfuration pathway that ultimately produces glutathione.

Foods and Drinks that Promote Glutathione Production

Last, we’ve come to our diets.

One study found that eating 83 grams of almonds daily increased glutathione levels by 16% in smokers, and decreased their DNA damage by 29%.

It has been well-established in research studies that there is a strong link between inadequate intake of sulfur-containing amino acids, and low GSH concentrations

That is because sulfur is an essential component in glutathione production, and it is found in cysteine.

Sulfur-rich foods include:

  • Garlic
  • Onions
  • Leeks
  • Chives
  • Broccoli
  • Brussels Sprouts
  • Cabbage
  • Cauliflower
  • Kale
  • Watercress

Selenium is another nutrient that is essential to glutathione. Specifically, the activity of many glutathione peroxidases, or GPx, depend on selenium and selenoproteins.

We’ll get into more detail on glutathione peroxidase later.

Selenium-rich foods include:

  • Yellowfin Tuna, cooked
  • Halibut, cooked
  • Sardines, canned
  • Grass-Fed Beef
  • Roasted Turkey, boneless
  • Beef Liver
  • Roasted Chicken
  • Cottage Cheese

Methylation nutrients, specifically folate, or Vitamin B9, Vitamin B6, and Vitamin B12, are essential to glutathione production in that the methylation cycle is directly linked with the transsulfuration pathway.

Now that we know what glutathione is and how to increase our intracellular levels of glutathione, we can finally get into:

How Does Glutathione Benefit Sleep?

Current research has suggested that more glutathione is produced when the body is asleep than during any other time. In addition, there is evidence of a link between higher glutathione levels and better sleep. This creates a cyclical effect of sorts:

It has been shown in numerous animal studies that sleep deprivation results in a significant reduction in glutathione levels. In 2012, the Progress in Neuro-Psychopharmacology and Biological Psychiatry journal published a study that investigated the effects of primary insomnia, or insomnia disorder, on certain biomarkers of oxidative stress. 

The healthy participants and patients with primary insomnia had their levels of glutathione, GPx activity, and malondialdehyde, a biomarker of oxidative stress in the body, measured.

It was shown that the patients with primary insomnia had higher levels of malondialdehyde, and significantly lower levels of GPx activity

The researchers concluded that sleep is crucial in decreasing oxidative stress.

Glutathione and Its Different Forms

Before we go any further, we need to talk about the different forms of glutathione.

Glutathione comes in two different forms:

  • GSH, also known as reduced glutathione, or L-glutathione
  • GSSG, also known as oxidized glutathione

As the antioxidant properties of the GSH molecules act on reactive oxygen species, also known as ROS or oxygen radicals, the molecules are oxidized and become GSSG. 

Oxygen radicals are unstable molecules containing oxygen that easily react with other molecules in a cell. They are naturally formed during the process of cellular respiration and as intermediates of many enzymatic reactions. 

However, overaccumulation of oxygen radicals may damage DNA, RNA, and proteins, and may cause cell death.

The ratio of GSH to GSSG determines the redox status of cells, which refers to the balance between oxidants, or pro-oxidants, and antioxidants. 

Healthy cells in a state of rest have a GSH/GSSG ratio of greater than 100

When cells are exposed to oxidative stress, then the ratio will drop to 1 to 10.

Glutathione peroxidases, or GPx, and glutathione S-transferases, or GSTs, are two groups of enzymes that make up the glutathione system and regulate the antioxidative effects of glutathione.

Now, let’s explore:

The Effects of GSH and GSSG in the Body

Another study performed at the Tokyo Medical and Dental University was done to examine whether GSH helps induce sleep in freely behaving rats. Up to the point that this study was done, it was already well-known that GSSG is a potent sleep-promoting substance from within the body.

It was in this study that it was demonstrated for the first time that GSH possesses sleep-enhancing effects.

This was done with an ICV infusion of GSH during a 10-hour nighttime period to the rats.

For reference: 

ICV, which stands for intracerebroventricular, is a method of invasive injection of substances directly into the cerebrospinal fluid in the cerebral ventricles. 

It is done to help bypass the blood brain barrier and get medications into the central nervous system. 

The sleep-inducing effects of 50 nanomoles per liter of GSH was comparable to those induced by 25 nanomoles per liter of GSSG

This is reasonable because, structurally, GSH makes up half of GSSG.

The researchers experimented on how NEM, which is an inhibitor of GPx activity, affected sleep.

The results?

These experiments clearly showed that, by slowing down or preventing the biosynthesis of GSSG from GSH, both NREM and REM sleep were strongly suppressed during its period of administration in the daytime. 

The researchers believe that GSSG, not GSH, is responsible for regulating sleep, and that the conversion of GSH to GSSG is required to promote sleep

They concluded that the biosynthesis of GSSG from GSH is responsible for the GSH-induced enhancement of sleep.

These same researchers also proposed that glutathione helps detoxify neurons on a cellular level while the body is asleep.

Liposomal Glutathione Supplements Further Increase Glutathione Benefits

If you are looking for ways to increase your intracellular glutathione levels, you should consider a Glutathione Supplement.

More specifically, you may want to do some research on Liposomal Glutathione Technology.

Liposomal Glutathione Technology uses micro sized fluid filled liposomes to protect and deliver nutrients directly into the cells and tissues of the body. These liposomes are very similar to human cells, which makes it easier for them to be transported within the body. As a result, nutrient absorption is greatly increased, and there is less intestinal discomfort than with using standard oral supplements.

Liposomal Technology provides several different advantages, including:

  1. Micro-sized encapsulation that protects against the harsh acidity of the gastrointestinal tract
  2. Increased delivery to cells, tissues, and organs
  3. Higher absorption rates and bioavailability than other standard oral supplements
  4. Noninvasive compared to intravenous supplementation
  5. Lower doses provide the same effects as high-dose standard oral supplements
  6. Helps put nutrients to use by the body faster
  7. Prevents gastrointestinal distress usually experienced with standard oral supplements 

Clearly, Liposomal Glutathione Supplement deserves serious consideration for its potential sleep aid benefits.

Why You Should Consider A Glutathione Supplement?

Glutathione is one of the most important antioxidants in the body that helps promote better sleep, detoxify the body while sleeping, and provide neuroprotective benefits. 

With improved quality of sleep, the body is able to produce even more glutathione, which causes a cyclical effect of improved sleep and detoxification.

You should take the necessary steps to keep your levels of glutathione within a healthy range during the nighttime for overall better sleep quality and improved antioxidant protection.