Trigger for autoimmune disease identified and link for chronic illness

Acetylcholine/Choline Deficiency in Chronic Illness – eat soft boiled eggs

To my friends who love to drink alcohol be it San Miguel beer or red wine, do eat protein rich foods like soft boiled eggs when drinking.

To my BFF with pancreas health issues, eat soft boiled eggs.

Connie

Acetylcholine/Choline Deficiency in Chronic Illness – The Hunt for the Missing Egg.

Those who lack choline are prone to mental illness, heart disease, fatty liver and/or hemorrhagic kidney necrosis and chronic illness as choline is oxidized to betaine which acts as an important methyl donor and osmolyte. With fatty liver, a person can be prone to diabetes and other chronic illness.  Eggs are rich in choline.  Choline is also found in a wide range of plant foods in small amounts. Eating a well-balanced vegan diet with plenty of whole foods should ensure you are getting enough choline. Soymilk, tofu, quinoa, and broccoli are particularly rich sources.

Eggs are an excellent source of choline and selenium, and a good source of high-quality protein, vitamin D, vitamin B12, phosphorus andriboflavin. In addition, eggs are rich in the essential amino acid leucine(one large egg provides 600 milligrams), which plays a unique role in stimulating muscle protein synthesis.

ucm278430We hear a lot about vitamins and minerals such as B12, folate, magnesium, vitamin C, and so on, but there seems very little talk these days on the importance of dietary lecithin and choline. Are you consuming an adequate amount of acetylcholine, or other phospholipids? The odds are that you are not.

A little bit about choline

The human body produces choline by methylation of phosphatidylethanolamine (from dietary sources such as lecithin and others) to form phosphatidylcholine in the liver by the PEMT enzyme. Phosphatidylcholine may also be consumed in the diet or by supplementation. Choline is oxidized to betaine which acts as an important methyl donor and osmolyte.

For those wanting to see how this relates to the methylation cycle, below is a nice graphic (courtesy of Wikipedia).

Choline metabolism

It is well known that magnesium deficiency is widespread (57% of the population does not meet the U.S. RDA according to the USDA), but the numbers for choline deficiency are even more shocking.

According the National Health and Nutrition Examination Survey (NHANES) in 2003-2004, only about 10% of the population have an adequate intake of choline. This means about 90% of the population consumes a diet deficient in choline. Furthermore, those without an adequate intake of choline may not have symptoms.

Along with folate and B12 deficiency, inadequate consumption of choline can lead to high homocysteine and all the risks associated with hyperhomocysteinaemia, such as cardiovascular disease, neuropsychiatric illness (Alzheimer’s disease, schizophrenia) and osteoporosis. Inadequate choline intake can also lead to fatty liver or non-alcoholic fatty liver disease (NAFLD).

The most common symptoms of choline deficiency are fatty liver and/or hemorrhagic kidney necrosis. Consuming choline rich foods usually relieve these deficiency symptoms. Diagnosing fatty liver isn’t as simple as running  ALT and AST since nearly 80% of people with fatty liver have normal levels of these enzymes according to a population study published in the journal Hepatology. In fact, in an experiment, 10 women were fed a diet low in choline. Nine developed fatty liver and only one had elevated liver enzymes.


Estrogen and Choline Deficiency

Given the connection between low lipids and choline deficiency, it would be tempting to think that as long as someone has enough cholesterol and TG that they will be protected from choline deficiency.  Unfortunately this is not the case.  Having adequate lipids does indeed help support healthy choline levels, but it does not guarantee a person will avoid choline deficiency.  The truth is that choline deficiency can come from more than one source.  Both sex hormone levels and genetic SNPs may lead to a choline deficiency by influencing the PEMT enzyme – the enzyme responsible for synthesis of choline inside the body.  Recent research now confirms how hormones and genetic polymorphisms play a major role in choline deficiency.

The body can make choline only one way; that is by methylating a molecule of phosphatidylethanolamine (PE) into a molecule of phosphatidylcholine (PC).  The body’s only method for accomplishing this is via the enzyme PEMT (phosphatidylethanolamine N-methyltransferase) which is found in the liver, brain, muscle, fat and other tissues.1,2    As with other well-known methylation enzymes like MTHFR and COMT, the PEMT enzyme can have genetic SNPs that slow it down.  When this enzyme slows down the body cannot make choline in high amounts and choline deficiency is more likely.  But there is more to the story of PEMT than just polymorphisms.  In addition to being slowed by SNPs, PEMT is also dependent upon the hormone estrogen for activation. 1, 3  What this means is that the PEMT enzyme, the body’s only method of synthesizing choline, has not one but two Achilles heals.  The PEMT pathway and how it relates to phosphatidylcholine production is shown in Figure 1.3 below.

Communicating Vessels4-PEMT

Figure 1.3 – PEMT is shown as the rate-limiting reaction in the production of phosphatidylcholine inside the human body.  Due to genetic and hormonal variances, most people have a PEMT enzyme working too slow and are susceptible to choline deficiency when there is not enough choline in the diet.  ACoA – Acetyl-CoA; TG – Triglycerides; PE – phosphatidylethanolamine; PC – phosphatidylecholine; PEMT – phosphatidylethanolamine N-methyltransferase.

As mentioned above, the sex hormone estrogen is intimately linked with the production of choline.  Women have a biological advantage here as the premenopausal female body has much higher levels of estrogen than does the male body.  When a woman becomes pregnant this advantage is taken to an extreme, as pregnancy increases estrogen levels over 30 times normal.4  A successful pregnancy requires high amounts of nutrients delivered to the growing baby, esp. choline.  Since the mother’s body is building a human being from scratch, there is an added burden on her biology to provide enough nutrition to her growing baby.  Viewed from this perspective, the high estrogen levels during pregnancy can be seen to act like a biochemical insurance policy.  Since the PEMT enzyme requires estrogen to function, pregnancy allows a woman to make extra choline for her developing child.  Furthermore, the nervous system is the first system to form in utero and is a tissue that requires high levels of choline for proper development.5, 6  Choline plays such an important role in cell membranes, myelin sheaths, and nervous system tissue that the high estrogen levels during pregnancy help make sure the growing brain and nervous system is nourished.  It is a genius system that assures the health and survival of the child.

Even though Nature has conferred an advantage to females by providing them with higher estrogen levels, esp. during pregnancy, this alone cannot protect against a lack of choline in the diet.  All the estrogen in the world will not save a woman from choline deficiency if the gene responsible for producing choline is slowed down by a polymorphism.  Genetic research has shown that the gene responsible for synthesizing choline, the PEMT gene, is susceptible to common polymorphisms which alter its function by slowing it down.  In a recent study looking at a population in North Carolina, men and women of various ages were placed on a choline-deficient diet.  They were followed closely for up to 42 days on a low choline diet consisting of less than 50mg choline per day.  Throughout the study, the participants’ liver function was continuously assessed for any sign of fatty liver and damage.  After eating a choline deficient diet for just six weeks, 63% of participants developed liver dysfunction and choline blood levels dropped 30% in every single participant, including premenopausal females.7  During this six week trial of low dietary choline the odds of developing liver dysfunction were 77% for men, 80% for postmenopausal women and just 44% for premenopausal women.7  Based on what has been discussed so far about estrogen and choline, it makes sense that men and postmenopausal women would be more susceptible to developing fatty liver since they don’t have high estrogen levels.  And based on the fact that estrogen levels drive choline production, premenopausal women should have been protected from fatty liver since they make higher amounts of choline – but that was not the case.

With dietary choline restricted to just 50 mg/day, approximately half of the premenopausal group also suffered liver dysfunction, suggesting that a choline deficient diet can even harm women with higher estrogen levels.  In addition, blood tests revealed that premenopausal female experienced a 30% loss of choline on a low choline diet right along with everyone else.   Despite the fact that higher estrogen levels allow fertile women to make more choline, many were not able to make enough to avoid problems.  A PEMT gene polymorphism is the only mechanism that can explain how women with high estrogen levels are still susceptible to choline deficiency when placed on a low choline diet.

Just like many individuals in the population, some of the premenopausal women inherited one or two copies of the PEMT gene which slows down the production of choline.   This study showed that fatty liver occurred in 80% of the premenopausal women with two copies of PEMT and in 43% with only one copy of PEMT.8  What this means is that a premenopausal woman with two copies of the slowed PEMT gene has exactly the same risk of fatty liver as a postmenopausal woman.  It is as if inheriting two copies of the PEMT gene effectively shuts off all estrogen-related choline production in the body.  If a woman only has a single copy of the slowed PEMT gene, she will still have a roughly 50% chance of liver dysfunction on a low choline diet.  Thus a single copy of the gene is only slightly better than two copies, as at least some estrogen-related choline production is preserved.

If having a PEMT gene can put one at risk for choline-related diseases like fatty liver, then it is important to know how common these genes are in population.  We know that 74% of all women in the study had a SNP in the PEMT that made their PEMT enzyme unresponsive to estrogen.9  This means that only 26% of women can make enough choline on a low choline diet; and that ability depends on whether the woman is still fertile or has entered menopause.  In this way genetics can take away the biological advantage that high estrogen levels usually offer to premenopausal females.  Women with these PEMT genes will be at risk for choline deficiency and liver damage just like all men and post-menopausal women – two groups who don’t have enough estrogen to make choline regardless of their genes.  Due to all the interference from the PEMT gene, dietary choline levels must be optimized for the vast majority of our population.

Summary of PEMT and Choline Deficiency:

  • In humans, choline is only made by the PEMT enzyme
  • Estrogen is required for the PEMT enzyme to activate and function normally
  • Men and postmenopausal women have an elevated risk of choline deficiency due to low estrogen levels.
  • The PEMT enzyme is commonly slowed down by polymorphisms, making it unresponsive to estrogen levels
    • 74% of women have at least one copy of a slowed PEMT
    • Homozygous carriers of PEMT have much higher risk of choline deficiency
    • Men, postmenopausal women, and premenopausal women with PEMT SNPs need to increase choline intake in the diet to offset elevated risk of liver dysfunction

The take away here is that studies have recently shown that because of common genetic polymorphisms, choline deficiency is a widespread problem.  Normally the hormone estrogen allows the body to make choline from scratch.  However, genetic variation in the PEMT enzyme, estrogen levels and gender differences prevent most people from making adequate choline.  Realistically then the only group in our population who is protected from choline deficiency are premenopausal females without a single copy of the slowed PEMT gene.   Every single male, every single postmenopausal woman, and 74% of premenopausal woman all require daily intake of approx. 500 mg of choline to prevent fatty liver, organ damage, and the associated health problems.7  If the body is already depleted, then levels that simply prevent deficiency won’t be enough to replete the body.  In these cases, higher daily doses of at least 1 gram or more are needed to replenish the tissues.  Choline it seems must be absorbed from the diet in just about everyone except for the few young women who have a normal PEMT gene and can synthesize choline regardless of dietary intake.


7 Ways How To Cook Eggs to Maximize Nutrition – Dr. Anthony Gustin

BEST TO WORST WAYS HOW TO COOK EGGS FOR MAXIMUM NUTRITION: 1. SOFT BOILED. We’ll start out with the best way how to cook eggs for nutrition: soft boiled. This is when you boil anegg, but it is still a little runny and the yolk is definitely not hard. It might take a little more work than other methods, but soft boiled …

raw yolks as choline source for ‘cetams? – Brain Health – LONGECITY

http://www.longecity.org › LONGECITY › Bioscience, Health & Nutrition › Brain Health

Oct 9, 2005 – I know that uncooked egg yolks are a source of choline (180-215mg?) and phosphatidylcholine. As I understand it, cooking the yolk kind of ‘denatures’ the choline and makes it unavailable. … Whole raw eggs are my source of choline and protien (and other stuff too).

Cooking eggs destroy it’s choline benefits?? : Nootropics – Reddit

Jan 9, 2013 – 8 posts – ‎5 authors

There is a lot of speculation out there as to whether cooking an egg decreases the amounts of choline it contains. Most of what I see online says that it does. However, I have yet to find any scientific evidence that is the case. In fact, the USDA has a choline fact sheet, which has cooked eggs having slightly …

Eggs, Choline, & Cancer | NutritionFacts.org

Oct 14, 2013 – soft boiled egg contains useable lysine. Boil the egg for another minute to hard state, the lysine is not useable. Lysine is needed for the body to make use of the next 5 most important essential aminoes so that other aminoes can be made by the body. Lysine is denatured at about 110 degrees. As the heat …

The Single Best Way to Eat an Egg – Health Wire

Mar 5, 2015 – If you choose not to eat your eggs raw, poached or softboiled would be the next best option. This leaves the yolk still runny and the … Eggs also contain choline, selenium, biotin, B vitamins, phosphorus, and more, making them are one of the healthiest foods you can eat. And, contrary to popular belief, …

5 Ways to Get More Choline in Your Diet: Secret of Radiant Living

The ideal sources of choline are animal foods like egg yolks and liver, which contain the most concentrated amounts of this nutrient and can be easily incorporated into the diet to meet … Veggies from this group, including cauliflower, cabbage, bok choy and broccoli, boast around 65 mg of cholineper cup cooked.

Soft-Boiled Science: Egg-cellently Cooked Eggs – Scientific American

Mar 28, 2013 – Hard-boiled eggs are commonly used for dying Easter eggs, but a softboiled egg can make a yummy breakfast or snack. How does … One large egg has about 75 calories, many essential nutrients, lots of high-quality protein, various vitamins, multiple minerals, choline, folate and riboflavin. Eggs can help …

How to Boil Eggs: The Hard Truth About Boiled Eggs – Dr. Mercola

Jun 7, 2014 – Eggs are a phenomenal source of protein, fat, and other nutrients, including choline and the antioxidants lutein and zeaxanthin. … While less “well done” eggs are still preferable (such as poached, soft-boiled, or over easy with very runny yolks), a hard-boiled egg makes a fine snack or source of protein for …

The Only Way to Get the Most Nutrition From Eggs – Waking Times

Feb 21, 2015 – This nutrient loss occurs regardless of whether the egg is removed from the shell (for example, during poaching) or left inside the shell during cooking (for example, during soft or hard boiling). If you compare the nutrient value of one large raw egg to one large hard-boiled egg in the latest version of the U.S. …

Eat Your Eggs! Choline and the Link With Fatty Liver – Fatty Liver Diet …

fattyliverdietguide.org › Fatty Liver Diet

Eat Your Eggs! Choline and the Link With Fatty Liver. eggs “Stay away from eggs if you want to be healthy. They have all that fat and cholesterol!” If you’re like most people, you began hearing that information in the 70s, 80s or 90s (depending upon your age). …. I eate boiled eggs but not the yolk because I don’t like them.

 

 

5 Steps to Kill Hidden Bad Bugs in Your Gut that Make You Sick by Dr Mark Hyman

DOCTORS ARE TRAINED TO IDENTIFY DISEASES by where they are located. If you have asthma, it’s considered a lung problem; if you have rheumatoid arthritis, it must be a joint problem; if you have acne, doctors see it as a skin problem; if you are overweight, you must have a metabolism problem; if you have allergies, immune imbalance is blamed. Doctors who understand health this way are both right and wrong. Sometimes the causes of your symptoms do have some relationship to their location, but that’s far from the whole story.

As we come to understand disease in the 21st century, our old ways of defining illness based on symptoms is not very useful. Instead, by understanding the origins of disease and the way in which the body operates as one, whole, integrated ecosystem, we now know that symptoms appearing in one area of the body may be caused by imbalances in an entirely different system.

If your skin is bad or you have allergies, can’t seem to lose weight, suffer from an autoimmune disease or allergies, struggle with fibromyalgia, or have recurring headaches, the real reason may be that your gut is unhealthy. This may be true even if you have NEVER had any digestive complaints.

There are many other possible imbalances in your body’s operating system that may drive illness, as well. These include problems with hormones, immune function, detoxification, energy production, and more. But for now, let’s take a deeper look at the gut and why it may be at the root of your chronic symptoms.

Symptoms Throughout the Body Are Resolved By Treating the Gut

Many today do have digestive problems including reflux or heartburn, irritable bowel, bloating, constipation, diarrhea, and colitis. In fact, belly problems account for over 200 million doctor’s visits and billions in health care costs annually. But gut problems cause disease far beyond the gut. In medical school, I learned that patients with colitis could also have inflamed joints and eyes and that patients with liver failure could be cured of delirium by taking antibiotics that killed the toxin-producing bacteria in their gut. Could it be that when things are not quite right down below, it affects the health of our entire body and many diseases we haven’t linked before to imbalances in the digestive system?

The answer is a resounding yes. Normalizing gut function is one of the most important things I do for patients, and it’s so simple. The “side effects” of treating the gut are quite extraordinary. My patients find relief from allergies, acne, arthritis, headaches, autoimmune disease, depression, attention deficit, and more—often after years or decades of suffering. Here are a few examples of the results I have achieved by addressing imbalances in the function and flora of the gut:

  • A 58-year-old woman with many years of worsening allergies, asthma, and sinusitis who was on frequent antibiotics and didn’t respond to any of the usual therapies was cured by eliminating a worm she harbored in her gut called Strongyloides.
    A 52-year-old woman who suffered with daily headaches and frequent migraines for years, found relief by clearing out the overgrowth of bad bugs in her small intestine with a new non-absorbed antibiotic called Xifaxin.
    A six-year-old girl with severe behavioral problems including violence, disruptive behavior in school, and depression was treated for bacterial yeast overgrowth, and in less than 10 days, her behavioral issues and depression were resolved.
    A three-year-old boy with autism started talking after treating a parasite called Giardia in his gut.
    These are not miracle cures but common results that occur when you normalize gut function and flora through improved diet, increased fiber intake, daily probiotic supplementation, enzyme therapy, the use of nutrients that repair the gut lining, and the direct treatment of bad bugs in the gut with herbs or medication.

A number of recent studies have made all these seemingly strange reversals in symptoms understandable. Let’s review them.

Research Linking Gut Flora and Inflammation To Chronic Illness

Scientists compared gut flora or bacteria from children in Florence, Italy who ate a diet high in meat, fat, and sugar to children from a West African village in Burkina Faso who ate beans, whole grains, vegetables, and nuts.(i) The bugs in the guts of the African children were healthier, more diverse, better at regulating inflammation and infection, and better at extracting energy from fiber. The bugs in the guts of the Italian children produced by-products that create inflammation, promote allergy, asthma, autoimmunity, and lead to obesity.

Why is this important?

In the West, our increased use of vaccinations and antibiotics and enhancements in hygiene have lead to health improvements for many. Yet these same factors have dramatically changed the ecosystem of bugs in our gut, and this has a broad impact on health that is still largely unrecognized.

There are trillions of bacteria in your gut, and they collectively contain at least 100 times as many genes as you do. The bacterial DNA in your gut outnumbers your own DNA by a very large margin. This bacterial DNA controls immune function, regulates digestion and intestinal function, protects against infections, and even produces vitamins and nutrients.

Can bacteria in the gut actually affect the brain? They can. Toxins, metabolic by-products, and inflammatory molecules produced by these unfriendly bacteria can all adversely impact the brain.
When the balance of bacteria in your gut is optimal, this DNA works for you to great effect. For example, some good bacteria produce short chain fatty acids. These healthy fats reduce inflammation and modulate your immune system. Bad bugs, on the other hand, produce fats that promote allergy and asthma, eczema, and inflammation throughout your body.(ii)

Another recent study found that the bacterial fingerprint of gut flora of autistic children differs dramatically from healthy children.(iii) Simply by looking at the by-products of their intestinal bacteria (which are excreted in the urine—a test I do regularly in my practice called organic acids testing), researchers could distinguish between autistic and normal children.

Think about this: problems with gut flora are linked to autism. Can bacteria in the gut actually affect the brain? They can. Toxins, metabolic by-products, and inflammatory molecules produced by these unfriendly bacteria can all adversely impact the brain. I explore the links between gut function and brain function in much greater detail in my book, The UltraMind Solution.

Autoimmune diseases are also linked to changes in gut flora. A recent study showed that children who use antibiotics for acne may alter normal flora, and this, in turn, can trigger changes that lead to autoimmune disease such as inflammatory bowel disease or colitis.(iv)

The connections between gut flora and system-wide health don’t stop there. A recent study in the New England Journal of Medicine found that you could cure or prevent delirium and brain fog in patients with liver failure by giving them an antibiotic called Xifaxan to clear out bugs that produce toxins their poor livers couldn’t detoxify.(v) Toxins from bacteria were making them insane and foggy. Remove the bacteria that produce the toxins, and their symptoms clear up practically overnight.

Other similar studies have found that clearing out overgrowth of bad bugs with a non-absorbed antibiotic can be an effective treatment for restless leg syndrome(vi) and fibromyalgia.(vii)

Even obesity has been linked to changes in our gut ecosystem that are the result of a high-fat, processed, inflammatory diet. Bad bugs produce toxins called lipopolysaccardies (LPS) that trigger inflammation and insulin resistance or pre-diabetes and thus promote weight gain.(viii)

It seems remarkable, but the little critters living inside of you have been linked to everything from autism to obesity, from allergy to autoimmunity, from fibromyalgia to restless leg syndrome, from delirium to eczema to asthma. In fact, the links between chronic illness and gut bacteria keep growing every day.

So what can you do to keep your gut flora balanced and your gut healthy, and thus overcome or avoid these health problems?

Five Steps to a Healthy Gut (and a Healthy Body)

Follow these five simple steps to begin re-balancing your gut flora:

  1. Eat a fiber–rich, whole foods diet—it should be rich in beans, nuts, seeds, whole grains, fruits, and vegetables, all of which feed good bugs.
  2. Limit sugar, processed foods, animal fats, and animal protein—these provide food for unhealthy bugs.
  3. Avoid the use of antibiotics, acid blockers, and anti-inflammatories—they change gut flora for the worse.
  4. Take probiotics daily—these healthy, friendly flora can improve your digestive health and reduce inflammation and allergy.
  5. Consider specialized testing—such as organic acid testing, stool testing (new tests can look at the DNA of the bacteria in your gut), and others to help assess your gut function. You will likely have to work with a functional medicine practitioner to effectively test and treat imbalances in your gut.
    And if you have a chronic illness, even if you don’t have digestive symptoms, you might want to consider what is living inside your gut. Tending to the garden within can be the answer to many seemingly unrelated health problems.

Please leave your thoughts by adding a comment below—but remember, we can’t offer personal medical advice online, so be sure to limit your comments to those about taking back our health!

To your good health,
Mark Hyman, MD

References

(i) De Filippo, C., Cavalieri, D., Di Paola, M., et al. 2010. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA. 107(33): 14691–6

(ii) Sandin, A., Bråbäck, L., Norin, E., and B. Björkstén. 2009. Faecal short chain fatty acid pattern and allergy in early childhood. Acta Paediatr. 98(5): 823–7.

(iii) Yap, I.K., Angley, M., Veselkov, K.A., et al. 2010. Urinary metabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched controls. J Proteome Res. 9(6): 2996–3004.

(iv) Margolis, D.J., Fanelli, M., Hoffstad, O., and J.D. Lewis. 2010. Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease. Am J Gastroenterol. Aug 10 epub in advance of publication.

(v) Bass, N.M., Mullen, K.D., Sanyal, A., et al. 2010. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 362(12): 1071–81.

(vi) Weinstock, L.B., Fern, S.E., and S.P. Duntley. 2008. Restless legs syndrome in patients with irritable bowel syndrome: response to small intestinal bacterial overgrowth therapy. Dig Dis Sci. 53(5): 1252–6.

(vii) Pimentel, M., Wallace, D., Hallegua, D., et al. 2004. A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing. Ann Rheum Dis. 63(4): 450–2.

(viii) Cani, P.D., Amar, J., Iglesias, M.A., et al. 2007. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 56(7): 1761–72.

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Contact Connie for holistic caregivers for homebound bayarea seniors, Motherhealth Inc at 408-854-1833 (text) and motherhealth@gmail.com