Acetylcholine/Choline Deficiency in Chronic Illness – mental, liver, kidney, heart and hormones

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.

References

1 Resseguie ME, da Costa KA, Galanko JA, et al. Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. J Biol Chem. 2011 Jan 14;286(2):1649-58.

2 Tehlivets O. Homocysteine as a risk factor for atherosclerosis: is its conversion to s-adenosyl-L-homocysteine the key to deregulated lipid metabolism? J Lipids. 2011;2011:702853. Epub 2011 Aug 1.

3 Wallace JM, McCormack JM, McNulty H, et al. Choline supplementation and measures of choline and betaine status: a randomised, controlled trial in postmenopausal women. Br J Nutr. 2012 Oct;108(7):1264-71. Epub 2011 Dec 15.

4 Guyton AC, Hall JE. Textbook of Medical Physiology, 11th ed.  Philadelphia, PA: Elsevier, 2006, p. 1033.

5 Sadler, TW. Medical Embryology, 10th ed. Baltimore, MD: Lippincott Williams & Wilkins, 2006, p. 86.

6 Steinfeld R, Grapp M, Kraetzner R, et al. Folate Receptor Alpha Defect Causes Cerebral Folate Transport Deficiency: A Treatable Neurodegenerative Disorder Associated with Disturbed Myelin Metabolism. Am J Hum Genet. 2009 September 11; 85(3): 354–363.

7 da Costa KA, Kozyreva OG, Song J, et al. Common genetic polymorphisms affect the human requirement for the nutrient choline. FASEB J. 2006 Jul;20(9):1336-44.

8 Fischer LM, da Costa KA, Kwock L, et al. Dietary choline requirements of women: effects of estrogen and genetic variation. Am J Clin Nutr. 2010 Nov;92(5):1113-9. Epub 2010 Sep 22.

9 Zeisel SH. Nutritional genomics: defining the dietary requirement and effects of choline. J N

Highest Average Expenses for Common Conditions

AHRQ Stats: Highest Average Expenses for Common Conditions

For the nine most commonly treated conditions among U.S. adults in 2013, the highest average expenses per person were for the treatment of heart conditions ($3,794 per person), trauma-related disorders ($3,070) and diabetes ($2,565). (Source: AHRQ, Medical Expenditure Panel Survey Statistical Brief #487: Expenditures for Commonly Treated Conditions among Adults Age 18 and Older in the U.S. Civilian Noninstitutionalized Population, 2013.)


Today’s Headlines:


Increased Physical Activity for Kids Would Have Health and Economic Benefits

If half of U.S. children 8 to 11 years old got the recommended amount of physical activity, the proportion of children who are overweight or obese would decrease by 4 percent, according to new research funded partially by AHRQ. This would save $8 billion in annual medical costs associated with obesity-related conditions, researchers concluded. Having this same 50 percent of kids receive the recommended amount of exercise would also avert approximately $14 billion in annual lost productivity costs over their lifetimes, researchers concluded. The article in the May issue of Health Affairs estimated that only 32 percent of children currently get recommended amount of exercise, which consists of 25 minutes of high-calorie-burning physical activity three times a week. The study authors concluded that increasing children’s physical activity should be a higher national priority, in part because possible savings substantially outweigh the costs of interventions promoting increased physical activity. Access the abstract.


Highlights From AHRQ’s Patient Safety Network

AHRQ’s Patient Safety Network (PSNet) highlights journal articles, books and tools related to patient safety. Articles featured this week include:

Review additional new publications in PSNet’s current issue or access recent cases and commentaries in AHRQ’s WebM&M (Morbidity and Mortality Rounds on the Web).


Nearly 6 of 10 Hospital-Based Surgeries in 2014 Occurred in Outpatient Settings

In 2014, 58 percent of the nation’s 17.2 million hospital-based surgical visits took place in outpatient settings, according to a new AHRQ statistical brief. The report from AHRQ’s Healthcare Cost and Utilization Project helps to quantify ongoing shifts toward more outpatient and fewer inpatient hospital-based surgical procedures. Among the most common outpatient surgeries in 2014 were lens and cataract procedures (nearly 100 percent performed in outpatient settings), cartilage removal in the knee (99 percent), tonsillectomy (96 percent), peripheral nerve decompression (95 percent), and hernia repair (92 percent). Private insurance was the most common payer for ambulatory surgery visits, while Medicare was the most common payer among inpatient surgical stays. For more data on inpatient and outpatient hospital-based surgery trends, access the statistical brief.


Study Questions Whether High-Priced Providers Deliver Higher-Quality Care

Patients who received care at higher-priced physician practices rated those practices higher than their lower-priced counterparts on measures of care coordination and management, according to an AHRQ-funded article published in the May issue of Health Affairs. However, patients’ evaluations were similar on overall care and services such as mammography, vaccinations or diabetes treatment, no matter the price, the research found. Authors defined higher-priced practices as those that charged 36 percent higher than lower-priced practices—on average about $84 for an office visit for a medium-complexity patient for higher-priced practices versus about $62 for the same type of patient visit at a lower-priced practice. The authors concluded that the findings suggest a weak relationship between practices’ prices and the quality and efficiency of care they provide. This research was funded by AHRQ’s Comparative Health System Performance Initiative, which studies how health care delivery systems promote evidence-based practices and patient-centered outcomes research in delivering care. Access the abstract.

Sugar , transfat and poor lifestyle – causes of American death in last 35 years

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Smoking , alcohol, meds/drugs and poor lifestyle (absence of exercise, clean water, air and whole foods) contributed to poor health in the southern part of the United States.

https://projects.fivethirtyeight.com/mortality-rates-united-states/cardiovascular/#2014

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diab 2.JPG

cancer 11

liver c

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pancreatic c

luekemia

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prostate

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esophageal

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colon 1

Pulmonary hypertension is higher among women over 85 yrs old

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There is an increase in mortality (2001-2010) associated with PH among men, women, and all race and ethnic groups, and from several conditions commonly associated with PH (hypertension and coronary heart disease, aortic stenosis, liver disease and cirrhosis, and autoimmune disease) but also from renal disease and diabetes, while finding that PH-associated mortality decreased over time from deaths due to congenital malformations among newborns, and for emphysema, chronic lower respiratory disease, and pulmonary embolism.

Approximately one-half of deaths associated with PH occur among those under 75 years of age. Although PH death rates have been stable for those aged 1 to 74 years over the past decade, the identified increases in PH death among those with a UCOD from hypertension, coronary heart disease, and valvular disease may be avoidable with improved public health efforts in the primary prevention of heart disease. The increased mortality from autoimmune conditions in association with PH requires further study. Increases in hospitalizations may reflect both improved recognition of PH as well as an increase in treatment options. The decline in PH mortality due to congenital malformations, chronic lower respiratory disease, and emphysema over time is encouraging.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122278/

More in blacks and women who are smoking

After 2003 death rates for women were higher than for men. Death rates throughout the reporting period 1999–2008 were higher for blacks than for whites. Hospitalization rates in women were 1.3–1.6 times higher than in men. Conclusions. Pulmonary hypertension mortality and hospitalization numbers and rates increased from 1999 to 2008.

Explanations for the older age include a change in the population age distribution, in the natural history of the disease itself (e.g., a change in some unrecognized intrinsic or extrinsic factor that delays disease manifestations), improved survival with therapy, or an increased prevalence of chronic lung disease in women due to secular trends in smoking among women. Our findings of excess PH mortality in blacks are generally consistent with the association between race and excess mortality from disease of the circulatory system in the United States

https://www.hindawi.com/journals/pm/2014/105864/

Associated with hereditary, connective tissue diseases, HIV

Familial PAH is now referred to as heritable, with further breakdown into the genetic abnormality identified, if any. Schistosomiasis and chronic hemolytic anemia are now part of category 1 disease as associated conditions to reflect their unique importance as causative factors of PAH. Chronic thromboembolic pulmonary hypertension is no longer divided into proximal and distal, as improvements in surgical technique make this partitioning obsolete. Finally, the miscellaneous category is expanded, and now includes many conditions previously included in the “other” category of associated PAH. The latter change recognizes the complexity and our poor understanding of the link between these conditions and pulmonary hypertension. PAH can be associated with a variety of known diseases, such as connective tissue diseases, portal hypertension, and human immunodeficiency virus (HIV) infection, in addition to the classic idiopathic form (see Box 1).

 

Box 1: Updated Clinical Classification of Pulmonary Hypertension, Dana Point 2008
1. Pulmonary arterial hypertension (PAH)
  • 1.1. Idiopathic PAH (IPAH)
  • 1.2. Heritable PAH
    • 1.2.1. BMPR2
    • 1.2.2. ALK1, endoglin (with or without hereditary hemorrhagic telangiectasia)
    • 1.2.3. Unknown
  • 1.3. Drug and toxin-induced
  • 1.4. Associated with (APAH)
    • 1.4.1. Connective tissue disease
    • 1.4.2. HIV infection
    • 1.4.3. Portal hypertension
    • 1.4.4. Congenital heart diseases
    • 1.4.5. Schistosomiasis
    • 1.4..6. Chronic hemolytic anemia
  • 1.5. Persistent pulmonary hypertension of the newborn (PPHN)

1′ Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH)

2. Pulmonary hypertension owing to left heart diseases
  • 2.1. Systolic dysfunction
  • 2.2. Diastolic dysfunction
  • 2.3. Valvular disease
3. Pulmonary hypertension owing to lung diseases and/or hypoxia
  • 3.1. Chronic obstructive pulmonary disease
  • 3.2. Interstitial lung disease
  • 3.3. Other pulmonary diseases with mixed restrictive and obstructive pattern
  • 3.4. Sleep-disordered breathing
  • 3.5. Alveolar hypoventilation disorders
  • 3.6. Chronic exposure to high altitude
  • 3.7. Developmental abnormalities
4. Chronic thromboembolic pulmonary hypertension (CTEPH)
5. Miscellaneous
  • 5.1. Hematologic disorders: myeloproliferative disorders, splenectomy
  • 5.2. Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleimyomatosis, neurofibromatosis, vasculitis
  • 5.3. Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders
  • 5.4. Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis

http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/pulmonary/pulmonary-hypertension/

Clinical Trends in 2016

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Alcohol, virus, sugar and fats lead to fatty liver

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Fatty liver phenotypes can help assess cardiometabolic risk in prediabetic patients

Insulin secretion failure, visceral obesity and fatty liver are three at risk phenotypes in people with diabetes.

Fatty change represents the intracytoplasmatic accumulation of triglycerides (neutral fats). At the beginning, the hepatocytes present small fat vacuoles (liposomes) around the nucleus (microvesicular fatty change). In this stage, liver cells are filled with multiple fat droplets that do not displace the centrally located nucleus. In the late stages, the size of the vacuoles increases, pushing the nucleus to the periphery of the cell, giving characteristic signet ring appearance (macrovesicular fatty change).

These vesicles are well-delineated and optically “empty” because fats dissolve during tissue processing. Large vacuoles may coalesce and produce fatty cysts, which are irreversible lesions. Macrovesicular steatosis is the most common form and is typically associated with alcohol, diabetes, obesity, and corticosteroids. Acute fatty liver of pregnancy and Reye’s syndromeare examples of severe liver disease caused by microvesicular fatty change.[6] The diagnosis of steatosis is made when fat in the liver exceeds 5–10% by weight.[1][7][8]

Mechanism leading to hepatic steatosis

Defects in fatty acid metabolism are responsible for pathogenesis of FLD, which may be due to imbalance in energy consumption and its combustion, resulting in lipid storage, or can be a consequence of peripheral resistance to insulin, whereby the transport of fatty acids from adipose tissue to the liver is increased.[1][9]

Impairment or inhibition of receptor molecules (PPAR-α, PPAR-γ and SREBP1) that control the enzymes responsible for the oxidation and synthesis of fatty acids appears to contribute to fat accumulation. In addition, alcoholism is known to damage mitochondria and other cellular structures, further impairing cellular energy mechanism. On the other hand, non-alcoholic FLD may begin as excess of unmetabolised energy in liver cells. Hepatic steatosis is considered reversible and to some extent nonprogressive if the underlying cause is reduced or removed.

Micrograph of inflamed fatty liver (steatohepatitis)

Severe fatty liver is sometimes accompanied by inflammation, a situation referred to as steatohepatitis. Progression to alcoholic steatohepatitis (ASH) or non-alcoholic steatohepatitis (NASH) depends on the persistence or severity of the inciting cause. Pathological lesions in both conditions are similar. However, the extent of inflammatory response varies widely and does not always correlate with degree of fat accumulation. Steatosis (retention of lipid) and onset of steatohepatitis may represent successive stages in FLD progression.[10]

Liver disease with extensive inflammation and a high degree of steatosis often progresses to more severe forms of the disease.[11] Hepatocyte ballooning and necrosis of varying degrees are often present at this stage. Liver cell death and inflammatory responses lead to the activation of hepatic stellate cells, which play a pivotal role in hepatic fibrosis. The extent of fibrosis varies widely. Perisinusoidal fibrosis is most common, especially in adults, and predominates in zone 3 around the terminal hepatic veins.[12]

The progression to cirrhosis may be influenced by the amount of fat and degree of steatohepatitis and by a variety of other sensitizing factors. In alcoholic FLD, the transition to cirrhosis related to continued alcohol consumption is well-documented, but the process involved in non-alcoholic FLD is less clear.


  • Non-alcoholic fatty liver disease (NAFLD) affects up to 25 percent of Americans, including children

  • If you have NAFLD, the first step for treatment should be to limit your fructose consumption to under 15 grams per day (including fruits)

  • Fructose is, in many ways, very similar to alcohol in the damage that it can do to your body… and your liver.

  • Eating right and exercising can often prevent this condition and may even reverse it in its early stages

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  • His findings were published in the Journal of the Academy of Nutrition and Dietetics,4 where Dr. Lustig explained the three similarities between fructose and its fermentation byproduct, ethanol (alcohol):
    1. Your liver’s metabolism of fructose is similar to alcohol, as they both serve as substrates for converting dietary carbohydrate into fat, which promotes insulin resistance, dyslipidemia (abnormal fat levels in the bloodstream), and fatty liver
    2. Fructose undergoes the Maillard reaction with proteins, leading to the formation of superoxide free radicals that can result in liver inflammation similar to acetaldehyde, an intermediary metabolite of ethanol
    3. By “stimulating the ‘hedonic pathway’ of the brain both directly and indirectly,” Dr. Lustig noted, “fructose creates habituation, and possibly dependence; also paralleling ethanol.”

Study explains the link between cilia and diabetes

cilia

Cellular extensions with a large effect

Tiny extensions on cells, cilia, play an important role in insulin release, according to a new study, which is published in Nature Communications. The researchers report that the cilia of beta cells in the pancreas are covered with insulin receptors and that changed ciliary function can be associated with the development of type 2 diabetes.

Cilia are tiny extensions on cells and they are credited with many important functions, including transduction of signals in cells.

Defects in have been implied in several diseases and pathological conditions. Thus, scientists at Karolinska Institutet in Stockholm, University College London and the Helmholtz Zentrum München (HMGU) took interest in the role of cilia in blood glucose regulation and type 2-diabetes.

“It has been known for some time that the rate of type 2 diabetes is above average in people with ciliopathy, which is a pathological ciliary dysfunction”, says Jantje Gerdes, previously at Karolinska Institutet and now at the Institute of Diabetes and Regeneration Research at the HMGU, first author of the study. “Our results confirm this observation and additionally explain how cilia are linked to glucose metabolism and diabetes.”

The researchers investigated the function of ciliary cell extensions in the insulin-secreting . Insulin is the hormone that reduces blood glucose levels. When the investigators stimulated the with glucose the number of on their cilia increased. When circulating insulin binds to the receptors it stimulates the release of more insulin into the blood. The cilia consequently play an important role in the release and signal transduction of insulin.

The investigators also studied what happens when the cilia are defective. They found that in mice with few or defective cilia the was reduced and the animals had significantly elevated .

“Ciliary dysfunction and defective glucose utilization are directly linked”, says Per-Olof Berggren at the Rolf Luft Research Center for Diabetes and Endocrinology at Karolinska Institutet, principal investigator of the study. “Ciliopathies therefore have a potential function as models in the investigation of many still unknown mechanisms that underlie diabetes.”

Explore further: Mechanism behind age-dependent diabetes discovered