Chris Masterjohn, PhD discusses why we should manage our glutathione status and how to do It

Why You Should Manage Your Glutathione Status and How to Do It

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Chris Masterjohn, PhD discusses why we should manage our glutathione status and how to do It

Glutathione is central to recovery from exercise, feeling good, looking good, aging gracefully, and preventing or overcoming both infectious diseases and chronic degenerative diseases. Episode 31 covers everything you need to know about why and how to manage your glutathione status.

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This episode is brought to you by US Wellness Meats. I use their liverwurst as a convenient way to make a sustainable habit of eating a diversity of organ meats. They also have a milder braunschweiger and an even milder head cheese that gives you similar benefits, as well as a wide array of other meat products, all from animals raised on pasture. Head to grasslandbeef.com and enter promo code “Chris” at checkout to get a 15% discount on any order that is at least 7 pounds and is at least $75 after applying the discount but under 40 pounds (it can be 39.99 lbs, but not 40). You can use this discount code not once, but twice!

This episode is also brought to you by Kettle and Fire bone broth. I use their 24-hour simmered bone broth as a source of glycine-rich collagen and other nutrients that slowly release from the bones and the marrow inside them. A team of chefs designed the recipe, so it’s delicious to the max.  And the state-of-the-art packaging makes it the only bone broth on the market that is cooked in the traditional way and has no additives or preservatives, yet stays shelf-stable for up to two years, making it easily available at a moment’s notice. Head to kettleandfire.com/chris to get $10 off your first order.

Show Notes for Episode 31

In this episode, you will find all of the following and more:

  •      00:35     Cliff Notes
  •      10:45      Introducing my new health and wellness packages
  •      13:25       The health benefits of glutathione: master antioxidant, central to liver detoxification and the defense against glycation, master controller of hundreds of proteins, mucus fluidity, bronchodilation, anti-aging, protection against diabetes and its complications including cataracts and cardiovascular disease, protection against Hashimoto's and other thyroid disorders, protection against infectious diseases by supporting the immune system, protection against congestion, COPD, asthma, and other lung problems.
  •      25:15       How to measure glutathione status
  •      30:28      The synthesis, recycling, and regulation of glutathione
  •      37:00      Practical strategies to improve glutathione status: protein, vitamin B6, carbohydrate, whey protein and raw milk, bone broth and collagen, magnesium, metabolic rate, polyphenols and other phytonutrients as Nrf2 inducers, glutathione in foods, N-acetyl-cysteine and glutathione supplements, insulin and insulin resistance, MTHFR mutations, glucose 6-phosphate dehydrogenase deficiency, niacin, riboflavin, and thiamin
  •  1:04:24      Tying it all together

Lab Tests Mentioned in Episode 31

Glutathione Lab Tests

Recommended: Health Diagnostics Research Institute (HDRI) methylation panel, which includes glutathione in its reduced and oxidized forms.

Acceptable, but not best: LabCorp glutathione

Related Lab Tests

Methylation genetics can be evaluated using your 23andMe raw data file with StrateGene.

Quest and LabCorp both offer glucose 6-phosphate dehydrogenase activity.

It is very difficult to find erythrocyte transketolase from labs commonly used in the US. Erythrocyte transketolase is the ideal marker of thiamin status. This British pathology lab offers it, as does this clinic in Barcelona, and this medical referral lab in London. Quest and LabCorp test thiamin concentrations in the blood, though this is mainly a marker of recent intake rather than long-term status.

LabCorp and Quest tests plasma B6.

Glutathione Redox Status Calculator

If you obtain plasma measurements of glutathione in its reduced and oxidized forms, you can plug them into this calculator to obtain your plasma glutathione redox status in millivolts (mV). This is an integrated number that summarizes the stress placed on your glutathione pool and the ability of that pool to protect you from oxidative stress and to maintain the proteins under its control in a healthy state.

For the calculation to be accurate, the measurements have to be from plasma (not from red blood cells or from other tissues) and have to be in μmol/L. You can obtain these measurements from the HDRI methylation panel.

Interpreting Your Glutathione Redox Status

While the data are far from ready for diagnostic prime time, I think it makes sense to view the optimal glutathione redox status as close to -150 mV. The range between -140 and -150 is associated with youth, and I suspect keeping it in that range over time will allow one to age more gracefully.

The average glutathione redox status for adults through the age of 45 is about -148 mV, with the majority having values between -140 and -150 and most having values between -130 and -160. After the age of 45, the average magnitude of the redox status decreases linearly with age by about 7 mV per decade.

When people between the ages of 44 and 85 are pooled together, smoking cigarettes is associated with an average loss of 9 mV, which is equivalent to about 13 years of aging.

Compared to people under 45 (-148 mV), nonsmokers in the next four decades (-137 mV), and smokers in the next four decades (-128 mV), asthma is associated with a much stronger decrement. Mild to moderate asthma is associated with -120 mV, and severe asthma with -94 mV.

Chronic alcoholism is associated with an average redox status close to -100 mV, an association that is more variable among nonsmokers and more consistent among smokers.

All of the data in this section is from observational studies, and the aging associations are cross-sectional in nature. We should keep in mind that no one has tracked individuals over time to see how their glutathione redox status changes over decades, and no one has shown that these represent cause-and-effect relationships. Nevertheless, there is a wealth of mechanistic information that makes it not only plausible but reasonable to view these as cause-and-effect relationships with enough confidence to act on them, so I think it makes sense to try to implement practical strategies to maintain the redox status in the range associated with health and youth.

Other Glutathione Links and Research Mentioned in Episode 30

My consultation services

My other writings on glutathione, rich in references, covering whey protein in raw milk and a variety of other topics.

My doctoral dissertation was on glutathione

A review on the synthesis of glutathione

Glucagon antagonizes the synthesis of glutathione

A review on Nrf2

Oral glutathione enriches tissue glutathione in mice treated with BSO, which blocks all glutathione synthesis, showing that it can be taken up by most cells in tact when needed.

Humans make about 185 mg of glutathione per day.

250 mg or 1000 mg of oral glutathione over six months improves glutathione status in humans.

Sublingual glutathione seems to offer advantages over regular glutathione and N-acetyl-cysteine during a three-week period, but is it more than three times better? That's how much more it costs.

Rhonda Patrick interview with Jed Fahey About Sulforaphane

Right now Jarrow oral glutathione is my preferred choice for a supplement.

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27 Comments

  1. Hi Chris. I am currently trying to correct my very low folate and b-12 levels with the methyl forms of both. I also started taking glutathione to help my very low glutathione levels as well. However, I recently came access the below information on a forum from a researcher of some kind stating the following:
    “Glutathione and glutathione precursors such as NAC and glutamine, undenatured whey. The glutathione induces immediate active b12 deficiencies, apparently by converting active methylb12 to inactive glutathionylb12 and rapidly excreting it. This then causes the methylfolate to be dumped from the cells in a process called the “methyl trap”. This leads to a high serum folate but a low cellular folate causing a severe folate deficiency with increasingly severe symptoms over time. This is often mistakenly called “detox”. NAC can produce these same folate and b12 deficiencies also misidentified as “detox”. ”

    I’ve never come across this information anywhere else, and wanted to get your opinion on this. I definitely don’t want to be negating my efforts to increase my b-12 and folate levels, but I also really need glutathione. Thank you in advance for any insight you can provide.

  2. Any precautions for taking glutathione for an elderly man with heart attack history? He has a lot of wheezing so there seems to be the need for it.

  3. Chris,
    This was a very fascinating episode, particularly because I have an asthmatic cat. Are you aware of any data on safety and dosage of oral glutathione for cats? We are trying to manage his symptoms with an inhaler per our vet’s recommendations, but as you may imagine this is quite difficult.
    Thanks,
    Daniel.

  4. Hi Chris,
    First, thank you for sharing all your work!
    I’m trying to understand how I, as a type 1 diabetic, fit into this picture (regarding glutathione status/production).
    So, is this correct: even though I take insulin injections throughout the day, but because that insulin is not going through the liver, I’m considered insulin deficient (for purposes of making glutathione)?
    And if that’s true, my best bet is to bypass that first step like you mention and supplement in some way? If I make sure to get enough glycine, maybe adding whey protein would be enough?
    Thank you!

    1. Hi Kira,

      How is it possible for you to take an insulin injection and have it not reach the liver?

      1. I understand that some of the injected insulin does reach my liver. From what I understand, with endogenous insulin, the pancreas releases the insulin into portal vein and it then all passes through the liver. Whereas with exogenous insulin, only some percentage of the insulin reaches the liver (I really have no idea how much).

        My question was in regards to this section you wrote:

        Maybe they are insulin-deficient because of type 1 diabetes. Then they’re going to have trouble with that first step of glutathione synthesis because they’re not getting the insulin response necessary to support the regulation of that first step. So providing gamma-glutamylcysteine bypasses that step and allows you to shortcut any kind of metabolic problems there.

        I understand of course that type 1s are insulin deficient in their natural, untreated state, but I think most if not all type 1s take insulin, so I assumed you were referring to treated type 1s. So I was trying to clarify that to know whether or not my exogenous insulin was enough to keep my glutathione production up to par.

        I’m way out of my league with this stuff, just trying to learn as much as I can. I’m trying to connect lots of dots here and will certainly need to reread these articles.
        Thank you!

        1. Kira, I’m also T1D (and also love Chris’s work). Chris can correct me if I’m wrong here but I think his diabetic example was referring to uncontrolled diabetes without enough insulin present. Or for a diabetic who is eating a low/very low carb diet and thus has a lower insulin requirement. I don’t know what the threshold would be in terms of how low carb do we need to get before insulin becomes the rate-limiting step. Perhaps you can test your glutathione status per Chris’s suggestions if you eat a low carb diet and see if you really need to supplement with whey protein or a glutathione supplement.

          Also, you are correct about the difference between portal vein insulin coming directly from the pancreas vs. subcutaneously injected exogenous insulin, however it’s kind of a moot point, because your liver MUST be seeing the insulin in order for your blood glucose to be under control. If your insulin wasn’t getting to the liver in sufficient quantity then your liver would run rampant and dump glucose all day and your BG would be very high. The primary purpose of insulin from a glucose balance perspective is to inhibit the liver’s production of glucose, since we know glucose disposal is largely (I believe as high as 80% in some studies) controlled by the concentration gradient and principle of mass action via GLUT-1. In other words, don’t worry about the difference between exogenous/endogenous insulin because if your blood sugar is in control, you can be sure your liver is responding to insulin.

          In my case, I do eat a low carb diet for the benefits of glucose control, and so I have been experimenting with Chris’s advice and I have been using undenatured whey protein and an S-acetyl glutathione supplement.

        2. Kira,

          Yes, the more you replace insulin, the more you stimulate GSH synthesis. But whether you get the same result as not being diabetic is a matter that I think is probably various shades of “no” to “not quite,” and perhaps in the ideal case of treatment “almost.”

  5. Chris, is it necessary to supply glycine and cysteine at the same meal, to have best glutathione synthesis? Is it even better to provide them at every meal to make a steady supply through the day?

    1. Virginie, I don’t know the answer to that. I suspect it doesn’t matter in the sense that a whole protein will provide sufficient amounts of all. Mainly that’s methionine, not cysteine, but some proteins such as milk do provide cysteine in appreciable amounts. I think the timing of glycine is mainly relevant to buffering extra methyl groups from excess methionine, but probably not meaningful for adequate glycine to support GSH synthesis when talking about consuming meat.

  6. Chris, thanks for all this great info, i never miss a show. You discuss using an oral glutathione supplement as superior to NAC. since i lean heavily on examine.com, i was suprised to see they have a strongly worded opinion that NAC is the superior form and use some of the same studies you cite. Can you comment on that. i see a graph like this showing NAC is a more effective intake and don’t have the expertise to unpack it.
    https://www.sciencedirect.com/science/article/pii/S2213231715000841

  7. Its been mentioned twice before but – Would love to hear about your thoughts on the Bulletproof Glutathione Force
    Per Dave Glutathione is not easily taken in by the cells. “less bio available”

  8. Hi Chris,

    As someone with asthma that is well controlled with a daily maintenance medication (Advair which is a combo of fluticasone and salmeterol – it is a bit expensive) do you think that glutathione supplementation could be a potential alternative? Would it be a good safeguard in addition? Are there any papers looking at glutathione supplementation as an effective way to control asthma.

    thanks!
    -Seth

  9. It looks like you have to have your doctor order the test you recommend. You didn’t mention that in the podcast, am I missing something?

    1. Chris, I understand your point about insulin being required to synthesize gamma-glutamylcysteine, however what confuses me is GSH status on a ketogenic diet. There are studies such as this one that show GSH is increased in the mitochondria on a KD diet: https://www.ncbi.nlm.nih.gov/pubmed/18466343

      And studies such as these that show depletion of GSH in the liver similar to acetaminophen toxicity studies, despite maintaining liver mitochondrial antioxidant capacity: https://www.ncbi.nlm.nih.gov/pubmed/20594978/
      https://www.sciencedirect.com/science/article/pii/S0969996110001920

      I’m really not experienced with this subject so I was hoping you could comment on GSH and antioxidant status in the context of a ketogenic (not just low carb/ low insulin) diet.

      1. Brennan, One is in the hypothalamus, and the other is in the liver. The liver is where most glutathione is produced and is a good index of total body glutathione. This can probably easily be explained by the fact that the ketogenic diet caused oxidative stress, and this had a hormetic effect on glutathione synthesis in the hippocampus, but that overall there was less glutathione in the body.

  10. Thanks for sharing your expertise on this fascinating topic, much appreciated. Is were any reason to believe that glutathione supplementation, either with liposomal forms or the Jarrow Formulas Reduced Glutathione that you recommend might decrease the body’s endogenous production of glutathione?

    Thanks for any thoughts on this you might care to share!
    Lilian

  11. Thanks for the info, Chris. I’ve decided to take the oral supplement for now. But if I were to consider the sublingual form, which supplement would be best? I just had a quick look on iHerb and I can only find one which is by Source Naturals. It only contains 50mg of glutathione and also molybdenum and riboflavin. I’d prefer a higher dose and one that only contained glutathione.

    I was also confused to see this: https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4536296/bin/fx1.jpg
    From this study: https://www.ncbi.nlm.nih.gov/pubmed/26262996
    Why did blood levels go down like that during the 3 weeks for oral glutathione?

    And could your body become dependant on supplemental glutathione? I’ve heard of people becoming dependant on hormones due to body stopping natural production, so I’m just wondering.
    Thanks again.

  12. Hi,
    I am just curious!
    In case of the presence of cataracts without being diabetic, is it true what Dr, Bates suggests that it could be just chronic fatigue or contraction of optical muscles?

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