Primal Challenge Journal (MamaGrok) page 112

[MamaGrok]

Excerpts from Brain-Gut 9, very related to me.

Obesity is an inflammatory brain condition. Where does the infection come from? The gut flora actually is what causes humans to become fat. It has to due with shear numbers and the species of bacteria in our gut. There is a particular flora that produces adiposity and obesity in humans. These bacteria make something called FIAF (Fasting induced adipose factor) that control this process. This factor blocks lipoprotein lipase (LPL) in fat cells. LPL allows us to convert dietary Free Fatty Acids carried in lipoproteins into neutral fats that are stored in adipocytes.

When our gut flora is complex and healthy, it has 100 trillion cells with 250 species. We tend not to make fat in this instance either! Moreover, when the bacteria are active metabolically due to the presence of simple sugars, production of FIAF ceases, and fat creation is signaled.

In those newly created fat cells, a protein called leptin is also produced, and acts as a score keeper for the brain of how much fat is stored in the body. This messenger is sent to the brain around midnight when we are sleeping allowing the brain to assess total energy balance in the body.

The chemical reaction basically is to extract as much oxygen from the food and leave behind carbon and hydrogen. This is essential what a ‘turd’ is in its basic form. In an anaerobic environment bacteria have an amazing capability to extract energy from food for its host, namely us. Bacteria have little ability to save any of this energy for them. The human body usurps their ability to be great energy extractors and uses it for itself. Your gut flora is what makes you fat and your gut flora is under control of hormones!

Since the human colon is anaerobic when we feed these bacteria a diet high in simple carbohydrates they extract the oxygen and and leave us with bowel gas and lower levels of FIAF.

So when the human host turns around and eats a fat laden ketogenic diet it creates a huge hormetic issue for our gut flora. They can not access the energy in these fats because there is no molecular oxygen present and the human host is not hungry at all because the presence of the fat in the gut is signaled to the brain via the vagus nerve.

The gut bacteria become starved, FIAF rises, and this makes the human host burn its own fat for fuel and fat stores are depleted. This is precisely how the dance between our gut bacteria and our own adipose tissues is supposed to work in normal conditions... Since our gut flora controls our ability to make and store fat what if I told you they also might control our desires for the foods that they really want, namely fiber and carbohydrates? Well, this is precisely what happens. The gut flora control the levels of neurotransmitters, agouti, ghrelin, and NPY in the peripheral and central nervous system and this drives us to want to eat things. I have covered this numerous times already in many past blogs. The type of gut flora we employ actually is tied to the appetite, desires, and to the reward of the food with respect to the brain’s frontal lobes. (central dopamine levels)

RADICAL THOUGHT: Food reward should not be thought of a concept intrinsic to foods, but of the type of gut flora we have living in our own gut!
The key factor for humans maybe that the human gut flora seems to be very susceptible to the environment it finds itself in before puberty and before total brain maturation occurs at 25 years old. It appears that the local environment we live in in our early life is quite critical to this dynamic duo. This implies that where we live, the sources of food we eat, and the light conditions required to grow the food are provided under are all encoded in our food and this is directly transmitted to our brain via our vagus nerve by these neurotransmitters in the gut.


How might the brain account for these things? Well, the brain looks at micronutrients coming in through the gut and translates these chemical signals into neurotransmitters that the brain circuits can understand and decipher. For example, when we eat a diet high in fructose (found at the equator) the gut and body respond in kind by causing an increase in absorption of iron, while causing a relative copper deficiency in cells. A copper deficiency is handled differently in both sexes. Women need more copper than men do. The reason is simple. Copper is required for the production of the enzymes which convert progesterone into estrogen. However, in men, more zinc is required to form the enzymatic machinery needed to convert progesterone into testosterone.
When we eat a diet high in fructose, this will also lower zinc levels in cells. This lowers testosterone in men. Higher fructose levels also cause a transient magnesium deficiency in all cells in both sexes when this occurs chronically. Acutely, it changes it at the intestinal brush border. I mentioned here in this blog that is precisely how diabetes actually begins. This lowers the magnesium available to make ATP(energy) if it goes on too long. This is why magnesium deficiency is so common in people who eat carbohydrates in a mismatched environment (T2D).

in a high light environments (think tropics or equator) humans can compensate for the higher fructose loads in their diet because higher levels of sunshine simultaneously increase vitamin D levels in our body. The higher sugar consumption in this diet, will drive up LDL levels and the free T3 levels in the thyroid which allows the LDL to convert to pregnenolone, DHEA, and testosterone because of the higher than normal environmental exposures to the sun... We can tolerate more inflammation from this type of diet because our immune system is in better shape!

When we live in a mismatched environment to light or carbs, we can not compensate well, so what happens? We begin to lose estrogen and progesterone in our brain and it begins to collect in our gut, our fat cells and in testes and breasts. The excessive estrogens can’t be cleared by the liver and the excesses lead to neolithic diseases when this occurs chronically. Light levels correspond to food sources everywhere on this planet. This also implies we are not well adapted for traveling long distances and seeing different food sources. Our gut was not designed for intercontinental travel it appears. Maybe this is why jet lag is not well tolerated? Moreover, it ruins the cortisol/DHEA/melatonin axis where light is a major player in the brain circuitry and this alters our gut flora. This maybe why the environment we grew up in has such fond memories for us and why we seem to adapt awfully fast when we return to it?

SO HOW IS THIS SIGNAL TRANSMITTED IN THE BRAIN?
Simple, it is the hormone response of the epigenetic signal given to us from the gut flora.
Our brain has more neurons in our gut than any other place in the body. We often call it our second brain. Moreover, the brain does not have a hard wired circuit to every single cell in the gut, or every bacteria in the gut, so it transduces the signal of these 100 trillion cells using a hormone response to modulate this signal. This is how the environmental signal of food is transmitted to the neural signal of the brain’s alphabet. This is why in Brain Gut 5 I told you hormones are the Rosetta Stone for deciphering what is best for the brain. I told you there to think of food as hormone information, not as a metabolic fuel.
We can decipher the message once we understand the language of the gut flora to the brain. This is why understanding hormones is critical to obtaining health.

BECOMING AN EPI-PALEO Rx TRANSLATOR OF HEALTH:
When we see an altered hormone panel in clinical practice it might signal something small now…If this continues long enough you will wind up with some major health changes that become very complex and very difficult to treat.

The most common way the gut flora is altered in our modern world is via indiscriminate carbohydrate and antibiotic use.

[MamaGrok]

If the gut flora is simplified simultaneously, as it often is, the person will develop hard stools like one would see on a Bristol Stool chart level one or two. This means that the fecal elimination time is increased and because of this the water based estrogens are reabsorbed and the levels in the body grow. This radically affects the progesterone to estradiol balance in women and in men it can be the cause of man boobs, decrease libido, premature ejaculation, lowered testosterone, a lowered vitamin D level, higher LDL cholesterol from alteration of the LDL receptor in the liver. (Ed. note: Constipation causes estrogen dominance!!)Sometimes the signaling can be so bad that it can produce enough estrogen from reabsorption of estrogen the is makes the cells think they enough estrogens, which signals the body to cease endogenous production. This can cause major hypothalamic signaling changes between the gut and brain that are commonly seen in binging, eating disorders, and infertility cases. When this happens abnormal signals are sent to the thyroid gland (CRH), making it think it has enough stopping the production of T3. This stops the normal hormone pathways from the conversion of LDL cholesterol to pregnenolone that we outlined in the Hormone 101 blog post.

This is why we can see dramatic changes in fecundity, in menstrual problems, fibroid production, excessive bleeding, excessive cramping and bloating and in serious hypothyroid situations where reverse T3 is through the roof on labs. Obesity, infertility, hypothyroidism and eating disorders are merely ‘train stops’ before the ultimate stop…….Cancer. (Ed. Note: Requiescat in pace, my dear Debbie L.)



Short-term memory loss that we kid about is actually minor brain damage. There are biologic consequences to all our decisions. In a surgical or a clinical situation when someone has this “slight brain damage” any new stressor pushes them over the edge. Think of getting a test done under a general anesthetic like an MRI or an ankle fracture set with ketamine. This stress can cause you to decompensate neurologically. Some of my patients have much bigger risks for post anesthetic issues than others. Those with significant alterations in their gut flora carry the highest risks in my view, as a neurosurgeon. I do things peri-operatively different in them than those who do not exhibit these symptoms. Delirium under the stress of life or an ICU become more common things these days because altered gut flora are now the primordial condition of our species in the western world.

[MamaGrok]

BG 11

The normal large circadian prolactin surge we should see at around midnight, after leptin enters the brain, does not happen if the patient has leptin resistance, sleep apnea, or has eaten food too close (within 3-4 hours) to bedtime.

This blocks leptin’s ability to enter the brain because insulin spikes block leptin from binding to its receptor in the hypothalamus. As mentioned above, this step is usually impaired if you are a post menopausal female as well. Just being post menopausal alone make you more insulin resistant (IR) because of the intrinsic loss of your progesterone to estradiol ratio. The reason is simple, most post menopausal women have a very altered circadian cycle to both carbs and to artificial light because their gut flora changes as their hormones change as they age. This happens in men as well who are in andropause. This is just not a women’s story guys! It happens to us too. We also know from new research that as we age our gut flora changes to a more simplified one that favors increase deposition of fat from our diets. This is fostered by alterations in our hormones as we age.

Age -> hormonal changes -> more simplified gut flora -> more fat deposition from diet -> altered circadian cycle to carbs & artificial light -> loss of preg:estradiol ratio -> more insulin resistant -> insulin spikes block leptin from binding to its receptor in hypothalamus -> leptin can't enter brain -> no prolactin surge at midnight

AM cortisol’s are low and this implies that their dopamine levels in their brain are also low too. To increase their central dopamine stores we can use a drug like cycloset and low dose metformin to help their blood sugars, protect their intestinal brush borders and lower the leakiness to ROS at cytochrome one. This increases their ability to clear superoxides created in their brain’s mitochondria.

These things can all be used to reset the circadian chemical clocks in the brain by altering the levels of adenosine in our cells. Adenosine is the cellular signal that signals our cells we are entering a night time phase or renewal. It rises at night because during the day time activity we use up all our ATP! Adenosine is the result of used up ATP.

Coffee and artificial light blocks adenosine receptors and this is why it destroys normal sleep cycles. Artificial light, especially the new LED lights and hologens, with its powerful blue light spectrum, speeds up our chemical clocks to cause massive mismatches. In clinical medicine, carbohydrates out of their growing season and artificial light also cause low AM and higher PM cortisol levels in humans and are often associated with T2D. This is why T2D’s always seem to have altered sleep and dietary issues with carbs and industrial seed oil PUFA’s. It is because our sleep clocks and metabolic clocks no longer work in unison because of altered cellular signaling due to inflammation caused by these mismatches.

In artificial light environments we find alterations in the gut flora because it become simplified. Simplified means lower shear numbers of bacteria and decreased species of bacteria. When this happens as we mentioned in Brain Gut 9, we dont not make enough vitamin K2 from our gut flora. This often will increase their androgen levels too. Often times, it may give them their lost libido back too.

It is all driven by a massive change in their hormones once they lose their period or in men when their androgens and vitamin D levels fall apart for many reasons. This is another reason I am a big advocate for bio-identical hormone optimization in women and men when it is required. This need is greatest in women who are warm adapted, because they have the worse PG/E2 ratios. The need is lower in the cold adapted females because their leptin levels are already low due to the cold protocols, and this implies that their hormone panels are not too far off the optimal path. Everyone’s mileage varies.

GH and testosterone keep a man’s heart and muscles in tip top shape. (IGF-1 shouldn't go down till around 50-55 in men, and testosterone never.) If inflammation destroys these levels earlier in life, the results can show up in their labs and injury history even in younger people.

PM women & men are very similar to diabetics. All diabetics are leptin resistant and that implies their hormones are disordered by the very nature of the biologic process. Diabetics get this disorder from altered light cycles and excessive carbohydrates out of season. PM get this too on a smaller scale when their ovaries fail...This is why I mentioned the medication Cycloset earlier. Cycloset was approved for diabetics in 2009, but few physicians even know about it, or how it works in our brain to reset the circadian clock once it has been fast forwarded by mismatches. It works on the brain to fix the circadian mismatch that light and carbs cause when they are used out of their normal cycles. We look for altered AM and PM cortisol levels on an adrenal stress index test for a clue this is happening. It eventually results in the brain by lowering the dopamine pathways centrally.
Cycloset actually raises your AM cortisol spike that we normally see in a normal humans. I covered this extensively in my August webinar for members on my site. It resets the cortisol/DHEA/melatonin axis of the hypothalamus. When the circadian cycle is off we usually see low melatonin levels. Low melatonin levels are consistent found in epithelial tumors. In modern humans all epithelial cancers rates are exploding. Melatonin is the third most important anti-oxidant in the human brain.

I believe the environmental mismatches that have gone on for decades are the real etiology for the modern epidemics we are seeing explode in medicine. It is due to a modern human never facing a true winter, and never giving the brain the appropriate sunlight and sundown stimulus it needs to function optimally.

KEY POINT: Diabetics and PM women get the same symptoms from the same lowered dopamine problem, but they differ in intensity and duration. When you add another environmental mismatch it just worsens the defect for those with peri-menopause, PM, or andropause. That is why modern medicine thinks T2D is a “carbohydrate” only issue.

Most diabetic,s and those in PM, menopause, and andropause are even more sensitive to artificial light after dark. It is now becoming a very common finding in research papers in cancer and metabolism, that this is a huge problem that has been in our blind spot. Artificial light by itself, makes us insulin resistant, lowers our sex steroid hormones, destroys vitamin D levels, and alters our gut flora so we do not make enough Vitamin K2. Chronic lowered vitamin K2 also makes us more IR too and pushes us closer to T2D as well. It also sets the stage for atherosclerosis, CAD, osteoporosis and strokes. I covered the mechanism of this extensively here in this blog.

KEY POINT: This is also why peri and menopausal women’s FBG go up once their ovaries have failed... If they are over 88 you likely have this issue as well. I pay attention to it. When we have have high normal blood glucose it is a sign of brain damage. High normal blood glucose causes the brain to shrink!

Moreover, these artificial lights also tend to be quite bright (because of halogen and LED uses today with massive blue light exposure) and completely un-yokes the normal circadian signals from the hormone response in the brain. Blue light is a powerful known disruptor of the SCN in the eye. When it is off, we age faster. We age faster when our hormone levels fall to their lowest levels on our labs. The hormone panel is the Rosetta Stone for humans.

[MamaGrok]

BG 7

HOly wow...

Women’s gut microbe populations change as pregnancy advances, becoming more like those of people who might develop diabetes. It now appears there is a special microbiota for pregnant women that develops during the first 5 months of pregnancy to allow them to put on massive amounts of weight without developing diabetes in a normal pregnancy. The reason they do not appear to develop diabetes is because during pregnancy their progesterone levels are massively raised (by their placenta if it is functioning well) while their cortisol levels stay flat to decreased. This is true of most normal pregnancies, but today in the modern world due to the older age of women at conception, now infertility issues and obesity are skyrocketing and as a result those switches no longer work well. Many obese, infertile, and older women have low progesterone and high cortisol’s before they get pregnant and this radically alters the gut flora to favor an obeseogenic status as their pregnancy progresses. This is why we often see gestational diabetes develop in these women with low progesterone levels as their fetus gets larger.

(BUt many women get GD w/o being old or fat... but often have had miscarriages...)

[MamaGrok]

Back to BG 11

Blue light after sunset reduces the prolactin surge we normally see in humans. When we see chronic lowered prolactin surges we also see lower growth hormone secretion during the anabolic phases of sleep. Lowered chronic GH secretion directly affects cardiac and skeletal muscle function because the process of autophagy is made less efficient as our life continues... This is why heart failure is strongly associated with low IGF-1 and low sex steroid hormone levels. When growth hormone is not released in normal amounts, it also decreases our lean muscle mass, and increases our body fat percentage in all our organs and in our body. This leads to slowly declining organ dysfunction... We can measure this process clinically by looking for falling DHEA level (bad) and a falling Growth Hormone level (also bad) as we age.

We know that just sitting around does not make you fat from many studies done on hunter gatherers and from studies on many predatory mammals in the wild who are sedentary for most of their day.

[MamaGrok]

I have so much to update on, but just have to stop and say that this week, the bloating and diarrhea have decreased DRAMATICALLY. The only changes?


- back to CT
- big increase in seafood

My guess is the CT. It's what I dropped at the start of summer, which is when this all seemed to ramp up so much.

[MamaGrok]

So you might be wondering how does leptin enter this circadian equation with food and light? The first step is leptin levels rise slowly for fours post dinner. At midnight leptin then enters the hypothalamus. Once it binds to the receptor two things occur. The first is a second messenger is sent to the thyroid to up regulate free T3 production to stimulate uncoupling protein 3 in muscles to burn fat liberated as we sleep at a higher metabolic rate. These fats are burned not as energy but as free heat at the muscles.

The key take home is it requires leptin sensitivity and ideal thyroid function at the muscle level. How do we maintain ideal thyroid function? ... The Epi-paleo Rx makes sure that everything the brain needs and thyroid needs are in the same evolutionary food packages. It also lowers inflammation and leptin levels best. It also provides ample iodine resources to maintain your free T3 levels regardlessSo you might be wondering how does leptin enter this circadian equation with food and light? The first step is leptin levels rise slowly for fours post dinner. At midnight leptin then enters the hypothalamus. Once it binds to the receptor two things occur. The first is a second messenger is sent to the thyroid to up regulate free T3 production to stimulate uncoupling protein 3 in muscles to burn fat liberated as we sleep at a higher metabolic rate. These fats are burned not as energy but as free heat at the muscles.

The key take home is it requires leptin sensitivity and ideal thyroid function at the muscle level. How do we maintain ideal thyroid function? ... The Epi-paleo Rx makes sure that everything the brain needs and thyroid needs are in the same evolutionary food packages. It also lowers inflammation and leptin levels best. It also provides ample iodine resources to maintain your free T3 levels regardless of your carbohydrate intakes.

Seafood has optimal nutrient density for humans. When one talks about nutrient density of foods, you are just studying the food values against other foods. It is really useless information that can lead to bad conclusions, when you do not consider the main metabolic actions of the mammal in question... With regards to humans, the human brain is a complete energy hog and it requires all the nutrients in seafood and not those in offal. If offal or skeletal meat were critical to forming a human brain, then we should see other predatory mammals that eat meat and offal routinely walking this planet with massive brains. In fact, we see the opposite effect. Eating meat and offal does not make a brain.

The second effect of leptin is via another second messenger: the coupled receptor with leptin bound to it, sends a message to the anterior pituitary to release prolactin from 12-2 AM. The prolactin release is required for proper control of sleep stages and yoking sleep and metabolism…..but the real benefit is this is the signal the hypothalamus uses to release pulsatile growth hormone release from 2 AM to 5 AM during sleep stages 2-4. This allows the process of AUTOPHAGY to be of maximal efficiency as we sleep. At sunrise, cortisol rises and so does ghrelin, a gut hormone. What does ghrelin do during the day to growth hormone secretion? It stimulates it pulsatile release during daylight hours. This means that proper growth hormone release is completely tied to proper circadian signaling. It is also means that an IGF-1 level is instructive to a mismatch to a clinician. When IGF-1 is low, this usually signals an alteration in the cortisol/DHEA/melatonin axis. This is why a lowered AM cortisol is tied to T2D and most neolithic disease states. T2D have some of the lowest IGF-1′s measured in clinical medicine. When IGF-1 is low this means the person body composition is also dramatically altered. Low growth hormone levels signal higher body fat levels (especially visceral fat) and lowered levels of lean muscle mass. People with low IGF-1′s tend to also have sleep disorders like obstructive sleep apnea. When your AM/PM cortisol levels is off because of artificial light you can not make growth hormone and your body composition declines rapidly. This is why people get fat and lose muscle mass when their light cycle is off.

IS LIGHT OR DIET MORE IMPORTANT TO T2D OR A PM WOMEN? A REVIEW:
Light is most important and it is not close. Why? Simple. Neurobiology of light is the answer because of how the human brain is wired to light.


People who have sleep apnea are generally obese, inflamed and leptin resistant and never get their pulsatile GH release at the correct times of the day and as a result autophagy is poorly functional in them. If autophagy is poor, they suffer more diseases and age faster because their sleep is uncoupled from their metabolism. They are chronically using old proteins enzymes that have not be renewed by sleep. When you use old proteins and enzymes chronically you have altered cell signaling and this favors neolithic disease generation.
Moreover these people can never burn their excess calories they take in from their diet or altered flora, as pure heat because the initial message of leptin was blocked from entering the brain so they remain fat. They can’t lose the weight either until they become leptin sensitive and lower inflammation. If you want to know why you are not losing weight look at your inflammation levels as why that is the case. When they do begin to lose weight, they notice a tremendous change in sleep efficiency. Sleep is designed to be restorative and is critical for weight loss.
Prolactin is the trigger for GH release at night. GH decreases abdominal fat cells and simultaneously increases your lean muscle mass and allows for major protein synthesis. Its levels fall off a cliff for most women after age 40 and for men after age fifty and there is a corresponding drop in the efficiency of sleep and autophagy. This is why older people sleep less than younger people. It is also why babies sleep so long, because they are in a massive growth phase body and brain wide. This is when their GH is being released when everything is working optimally. This also fuels their brain growth too with optimal progesterone and cortisol levels. When these hormones are off our brain function takes a direct hit.



Ugh, I've been feeling, today & yesterday, that itchy feeling of wanting to do NOTHING, yet wanting to search everything on the computer at the same time. I don't want to address the chaos piling up in my home. I hate when these moods come in. BEGONE thyroid crap!

[MamaGrok]

When will I ever catch up? Dr. Kruse says I almost certainly have Hashimoto's and have since I was young.

Last night I spent an hour in LITERALLY labor-like waves of pain. 60s of increasing and decreasing intensity, 2-3m in between, INTENSE (like transition, seriously), except in my gut instead of womb. Then an hour of nothing. Then everything out. Only thing I can find is small bowel obstruction. But then it clears? I had a RUQ ultrasound, but I always have this back-of-the-mind thing that there is a tumor or something in there somewhere.

Right now, I think my thyroid is sore. When I touch where I think it is, it doesn't like it. It's hard, slightly sore, very sore if I press, and gag-y the more I press.

[Horsewoman]

Ouch that doesn't sound much fun. Hope you can get it sorted out soon and it isn't anything too worrying. Gall bladder been check I assume?

I thought my thyroid felt weird but it turned out to be spasms of a schincter in the esophagus due to acid reflux, which is thanks to it all being weak due to the weak collagen! Never knew weak collagen could do so many things!

[MamaGrok]

Gall bladder ultrasound came back with nothing unusual. I don't believe it, lol.

More sobering stuff I'm putting here to come back for easy reference:
from LR monster thread:
The Hashimoto's thing......it makes up 95% of all hypothyroid human cases today and it treated by medicine with CW. Most who have it have leaky guts and low levels of intracellular glutathione. Glutathione is a very important antioxidant that plays an important role in maintaining the correct oxidation-reduction potential inside cells. It scavenges oxidising free radicals, detoxifies heavy metals, pesticides, tylenol and leukotrienes. It stores and transports amino acids, regulates the cell cycle, protein synthesis and gene expression, and protects thyroid cells from self-generated hydrogen peroxide. Glutathione is quite important for patients with Hashimoto's. Glutathione protects the body in an extraordinary number of ways, but the fact that it protects the thyroid against hydrogen peroxide is particularly significant for the thyroid. In untreated Hashimoto's, the body's levels of T4 (thyroxine) begin to fall, and TSH (thyroid stimulating hormone) levels generally start to climb. In order to stimulate the thyroid to make more T4, the TSH activates the thyroid cells to make hydrogen peroxide. If the TSH levels remain high, the thyroid cells continue to produce more and more hydrogen peroxide, and this can lead to increased inflammation, scarring, and ultimately the destruction of thyroid cells. If the hydrogen peroxide manages to gain entry to the cell, the damage becomes far worse.

Hydrogen peroxide is thought to play a significant role in the development and progression of Hashimoto's disease, despite the fact that the thyroid gland actually requires hydrogen peroxide for thyroid hormone formation. Hydrogen peroxide is normally produced during the oxidation of the iodine ions. It is an essential part of the thyroid function. But the critical factor is the protection of the thyroid cells (glutathione level), and the place in which the iodine ions are oxidized. If oxidation occurs inside the cells, the hydrogen peroxide is produced inside the cells, and the cells sustain damage.

A study found that if hydrogen peroxide is allowed to enter thyroid cells, it attacks and cleaves thyroglobulin (protein within the thyroid), producing fragments that are able to diffuse into other cells – and these fragments were recognized by autoantibodies taken from people with Hashimoto's disease. This suggests that hydrogen peroxide entry into thyroid cells may actually be the cause of Hashimoto's disease!!!! SO if you have Hashimoto's your glutathione levels maybe a proxy of how bad your disease really is. It can be a measure of really how leaky your gut is too.

The predominant infiltrating cells in autoimmune diseases such as Hashimoto's thyroiditis are phagocytic macrophages, neutrophils and various T-cells; the macrophages and neutrophils damage the tissues by releasing inflammatory cytokines and proteins, including hydrogen peroxide making things worse because this further depletes glutathione inside the cells. This is complicated by co-morbid B12 and folate deficiencies in the diet because of the leaky gut. Glutathione requires both to be on hand to work well!

The body's stores of glutathione can become depleted through any stressor. For example, alcoholism, HIV infection, cirrhosis, diabetes, surgical trauma, fasting, environmental toxins, overuse of acetaminophen, chronic stress, inadequate diet, elevated adrenaline release, extensive strenuous exercise, or infection. It is also associated with cigarette smoking, as smoking increases the rate at which the body uses glutathione.

Glutathione is not easily absorbed through oral supplementation, but is synthesized in the body from amino acids, and body levels can be increased through oral administration of glutathione precursors such as N-acetylcysteine (NAC), S-adenosyl-L-methionine (SAMe) and L-gluatmine. Getting it into cells is even tougher and requires IV infusions using lipid soluble mediums. For serious autoimmune diseases it is often a great treatment. Oral administration of NAC of doses up to 8,000 mg/day was not found to cause clinically significant adverse reactions, although doses of 600mg/day were enough to significantly improve symptoms of chronic lung disease like COPD. I have used over 3000 mgs a day when my HS-CRP was around 3.0. When I have falls in Vitamin D levels I also reach for NAC or sometimes WHEY protein. Whey also breaks down into glutathione and reduces inflammation. This is why Whey use can augment weight loss in people with high CRP's

Intake of NAC does increase zinc loss through urine, so zinc supplementation would be advisable for anyone supplementing NAC over an extended period. This can deplete your sex steroid hormones if you do not eat a lot of foods with zinc. Me personally when I take a ton I always make my oysters rockerfeller recipe.

Glutathione can also be up-regulated by vitamins C and E, and alpha lipoic acid, PQQ, spinach, offal, yeast extract, and broccoli. N-acetylcysteine is considered to be the most effective, fastest route to raising levels of glutathione. It also increases levels of glutathione only when there is an actual need, and it seems to concentrate only in tissues where glutathione is required. This need corresponds to high MMP9 levels in cells.

The fact that NAC is able to restore glutathione levels and thereby protect the thyroid is particularly interesting given its ability to crack open bacteria such as chlamydia pneumonia, which hide inside the body's own cells during one part of their life cycle, using the host cell's machinery to replicate. Chlamydia pneumoniae has been implicated in autoimmune diseases such as multiple sclerosis, and N-acetylcysteine is considered an important part of treatment. I do not consider these diseases as part of AI's. I consider finding titers of these in patients to be patho-mneumonic that glutathione levels are very very low in these people.