People are always asking me to put my Hep C findings into simple language and keep it short. It's hard to do this without cutting corners. But increasingly I find things falling into simple categories, each of which can be explored seperately.
Hepatitis C in 5 words or less
A Hep C protocol should protect against the following aspects of HCV infection:
Oxidative stress (liver damage, diabetes, inflammation) – Hep C depletes antioxidants, low antioxidant levels are associated with poor outcomes. The combination of oxidative stress and hypomethylation is the preventable cause of hepatitis, fibrosis, and cirrhosis.
Some genotypes also promote the accumulation of iron, which increases oxidative stress exponentially. Genetics, iron fortified foods, and poor liver function can also add to iron loads.
Treatment – mixed antioxidants (selenium ACE type), Co-enzyme Q10, silymarin, polyphenols, OPCs.
Hypomethylation (steatosis, fatigue, depression) – Hep C depresses methylation, which allows fats to accumulate and decreases energy output. Methylation is the process needed to supply creatine, phosphatidylcholine, carnitine, co-enzyme Q10, glycine, melatonin, adrenaline, cholesterol and steroids; methylation also inactivates histamine and niacinamide, and helps with detoxification. Methylation also plays a role in DNA synthesis and in regulating the expression of genes and the activity of proteins. All methylation in the body is carried out by the SAMe form of methionine, except for the methylation of methionine itself, which requires B12, folic acid, and/or betaine. Hypomethylation (deficient methylation) in Hep C is largely due to inhibition of vitamin B12 by oxidative stress, the poor absorption of B12 and folate when stomach acid is inadequate, and anorexia and nausea limiting intake of foods rich in methionine. So-called low fat foods that are low in high-quality protein and essential fats and high in carbohydrates are especially problematic - the liver synthesises fats from carbohydrates in any case. Overcooked fats and refined oils and spreads should be avoided, vegetable oils minimized, some PUFA from fatty fish (omega 3 EFAs) and extra virgin olive oil is acceptable but most fats should come from red meat, cream and butter, dripping, and coconut.
Treatment – l-methionine or SAMe, B12, folic acid, phosphatidylcholine (lecithin), carnitine, betaine.
Immunosuppression (HCV replication, co-infections, allergies) – Hep C interferes, both directly, and via oxidative stress, with immune function, allowing co-infections and autoimmune syndromes to develop. Increased levels of interferons during illness can bring about gluten and other allergies in previously tolerant individuals.
Treatment – selenium, probiotics, zinc, vitamin A, vitamin D, vitamin C, cordyceps, astragalus, garlic, echinacea.
Note on antiviral herbs: Ginger, silymarin, grape seed OPCs, green tea extract, blueberry leaf extract, Rosa Rugosa flowers, various iridiods, stevia all directly inhibit HCV cell entry or replication; resveratrol enhances HCV replication.
Inflammation (other inflammatory conditions, liver damage, mood disorders) – Hep C increases production of pro-inflammatory cytokines, which can promote fibrosis, and prostaglandins, which strip essential fatty acids from cell membranes, causing pain and mood changes. Inflammation and oxidative stress are closely related. Similar processes are involved in PMS, bipolar disorders, psychosis etc. so it is not surprising that moods, emotions and perceptions can be affected by Hep C. Inflammatory cytokines can also trigger sensitivity to complex proteins such as gluten (wheat, rye, barley) and casien (cow's milk), which then become an additional cause of inflammatory disease.
Treatment – magnesium, vitamin D, ginkgo, EPA and DHA (krill oil is the best source), niacinamide, N-acetyl-glucosamine (glucosamine can be an effective substitute for NSAIDs). Gluten free, low carbohydrate diet high in saturated fat.
Detoxification (liver damage) - Exotoxins and endotoxins requiring phase 1 and phase 2 detox – drugs, toxins, pollutants, cholesterol and steroids - must be processed by liver and kidneys. Many of the phase 2 reactions use glutathione, glycine and taurine, levels of which are reduced in Hep C, and pantothenic acid (B5). Glycine production is inhibited by hypomethylation. Improperly metabolized toxins can add to oxidative stress, damaging the liver, or inhibit enzymes, impairing liver function.
Treatment – sulfur amino acids, B vitamins, broccoli sprouts, whey protein
Wednesday, 7 December 2011
Hepatitis C, Gluten and the Folly of Agriculture
Gluten and Casein as Factors responsible for the Characteristic Diseases of Chronic Hepatitis C
Not everyone exposed to HCV develops a chronic infection. The rate of natural clearance is unknown, because most people are not aware they are infected until the condition becomes chronic. One known factor in chronic infection with viral hepatitis (A or B) is selenium deficiency in malnourished populations. Celiac disease, the most easily diagnosed form of gluten toxicity, is known to cause selenium deficiency in well-fed populations. Celiac also causes a general deficiency of many antioxidants, protein, and minerals and vitamins. There is a strong association between HCV and celiac disease in many populations tested. There is an even stronger association between interferon-alpha treatment and celiac disease. Interferon-alpha is the cytokine that triggers celiac disease naturally. Celiac disease is only the easiest to diagnose of the gluten sensitivity syndromes. It results in destruction of the intestinal cell vilii, damage which can be detected on biopsy. Even so celiac is seriously underdiagnosed. It is likely that anyone in New Zealand with the symptoms of celiac disease, who is HCV positive, will be told that their symptoms are due to hepatitis C. Testing for Celiac will happen slowly and most likely not at all, unless the patient insists, and testing for other forms of gluten sensitivity is unlikely.
Milder forms of gluten sensitivity might only disrupt those gut receptors responsible for functions such as immune regulation (especially endorphin receptors), mineral transport, or absorption of specific vitamins. Antibodies may form to the proline-rich gluten, gliadin and casein sequences released by peptide digestion which enter the bloodstream, which then attack the proline-rich collagenous tissues, promoting diseases such as liver fibrosis and rheumatoid arthritis. It so happens that the auto-immune symptoms associated with celiac and gluten sensitivity diseases, including liver and gall-bladder disease, and which usually resolve slowly on a strict gluten and dairy-free diet, are essentially identical to the various syndromes seen in chronic Hep C, especially during or after interferon-alpha treatment. Syndromes caused by gluten in celiac disease include: - fibrosis and cirrhosis of the liver - gall bladder obstruction - insulin resistance - thyroiditis - sicca syndrome (dry eyes and mouth) - vasculitis - brain fog (poor memory, confusion) - depression - fibromyalgia - fatigue - optic neuritis - deficiencies of selenium, magnesium, zinc, chromium - deficiencies of fat-soluble vitamins (A, D, E, K) - deficiency of those vitamins converted in the intestines (including folate, B6) - anaemia - thrombocytopenic purpurea (low platelets due to autoimmunity) - GI disturbance; diarrhea, steatorrhea These symptoms are aggravated by the nutrient deficiencies, especially antioxidant, magnesium, and chromium deficiencies, associated with gluten sensitivity. In fact, the symptoms of both Hep C and celiac disease are often partially, but significantly, relived by supplementation of these nutrients, especially when anti-inflammatory botanicals (curcumin, grape seed, ginkgo, milk thistle etc) are added.
Other treatments effective against Hep C have obvious links to gluten sensitivity; for example, low dose naltrexone may exert its beneficial effects on cancer, autoimmune disease, and viral immunity by repairing damage done to endorphin receptors by gluten and casein digests. Similarly, enzyme therapy for cancers may work by promoting the complete digestion of gluten and casein exorphins, and the ketogenic diet for cancer may work by eliminating grains and lowering insulin levels (and hence inflammation), rather than merely by depriving cancer cells of glucose. Exorphins are chemicals found in protein digests (the peptides produced by pepsin digestion of food proteins) which have an affinity for endorphin receptors. Endorphins are the messengers of emotion, and gluten sensitivity is very often found in schizophrenia, autism, ADHD, Aspergers, and the various mood disorders. However, the endorphin system also regulates the immune system, and defects of endorphins and endorphin receptors are associated with cancers and autoimmune disease, as well as AIDS. Endorphins also regulate gut motility; the well-known constipating effect of cheese is an opioid effect. Even people who have no gluten antibodies and no leaky gut (which allows gluten digests to enter the bloodstream in especially large doses) are influenced by the opioid effect of exorphins at the local, gut level.
Diagnosing non-celiac gluten and casein sensitivity without exclusion diets is difficult, if not impossible. Commonly in New Zealand a scratch test for gluten is the doctor’s first choice. This is worse than useless, because we are not talking about an allergy to gluten at all (though these do exist). When gluten, milk and maize are digested in the stomach (by pepsin and hydrochloric acid) a variety of peptides are released. The exact combination of peptides that might appear in the gut varies with the individual, the state of his digestion, and the strain of wheat, milk or maize consumed. Gliadomorphin is a characteristic wheat exorphin; beta-casomorphin-7 is thought to be the most toxic milk exorphin; and the maize exorphins have not yet been identified. Autoimmune reaction to antigenic peptides is not the only way in which exorphins can harm us, so the current insistence on immunological testing seems limited. Also, current tests do not include antibodies to every possible peptide digest of gluten; this would probably be impossible. Further, in many cases symptoms may be due not to gluten but to agglutinating lectins found in the germ, or to phytates withholding nutrients (minerals and vitamin D), or to some synergy of all 3 components.
Luckily, no-one needs to eat grains. Our ancestors got along in better health without them for millions of years. Grain consumption is a comparatively recent phenomenon in human history; very recent indeed in some cases; in Northern Europe and in colonized Oceania it is a habit of mere centuries, if that. In parts of the world where grain-eating goes back longest, for example the eastern Mediterranean, there is a higher rate of adaptation. This does not mean that individuals adapted to grains; individuals died young or became sterile if they lacked the more grain-adapted genes, in order that the race might adapt. But this still does not rule out the diseases of later life. Study of remains of grain-dependent societies, such as Rome and ancient Egypt, show that so-called “modern” diseases such as arthritis and cancer were prolific there. It is trendy to think that such disease results from technology; radiation, pesticides, food processing; and that it can be prevented with an organic vegetarian diet. The sad truth is that in most cases wheat and milk - even organic wheat and milk – products of the older agricultural revolution – are doing more harm than those traces of the modern industrial revolution that we cannot avoid. If our immune systems and our detox enzymes cannot cope with some new agricultural chemical, the most likely reason is the disruption they have received from the old agricultural chemicals – gluten and casein.
It was also agriculture, not food processing, that first placed man in a guilty relationship with his food. Pre-agricultural man killed to eat and took from the forest, and had rituals that made peace with the animals and the plants. He took from these bounteous gods, not from captive creatures. Agricultural man kills for money, pays others to kill for him, and burns down the forest to plant his cash crops. If this was original sin, then the wages of sin have indeed been death.
It is customary to blame lead piping for the decline of Rome. The Roman people were highly wheat-addicted; they would riot for bread; “Bread and Circuses” was the formula for keeping them happy; they were so addicted that the state found it more convenient to supply bread for free (like a methadone clinic for the opiate of the people). Today the state oversees the addition of gluten, milk and maize to an ever-widening range of foods, so that a mere bread shortage is not likely to cause withdrawals. This is probably not intentional; addicts tend to assume that everyone wants to share their habit. In the case of Rome, wheat and lead may have had a synergistic toxicity. Both lead poisoning and wheat consumption tend to reduce iron and zinc absorption. This is why celiac children are often of short stature. The Romans would have become increasingly incapable of sensible planning and come to lack the stern old Roman self-control. We know that a decreasing birthrate of “true born” Romans eventually led to the conscription of barbarian armies and the opening up of Roman citizenship. Today gluten, and the antioxidant deficiency it causes, is a major cause of infertility.
Research has been done into the links between gluten sensitivity and Hep C, showing a strong association (especially after interferon therapy). There is also a strong association between Hep C and lymphoma (a cancer of the lymph glands). Lymphoma is the characteristic cancer caused by gluten; celiacs have a 30x elevated risk of lymphoma. To date no-one seems to have tested a strict gluten- and dairy-free diet for chronic Hep C or post-interferon toxicity, but a great many people with Hep C who take their health seriously have gone gluten free, often without knowing of the links between the two conditions, but motivated by their own well-being when avoiding gluten.
There is no nutritional need that can only be met by grains; nuts and seeds, for example, supply the same amino acids, fats and vitamins in greater concentration (for example, sunflower and sesame seeds are superior sources of methionine and vitamin E), while legumes are rich in complex carbohydrates. Gluten is also a cause of insulin resistance, and everyone who develops liver fibrosis has some degree of insulin resistance. Gluten itself causes a four-fold rise in insulin levels (unusual for a protein). The cure for insulin resistance is two-fold; a high-protein, low-carb diet (the Paleolithic diet is the most natural version of this diet) and replacement of the nutrients depleted by gluten which are essential for the function of insulin receptors; chromium, magnesium and the antioxidant minerals and vitamins. Gluten also seems to cause amino acid deficiencies, including some of the very amino acids which wheat is supposed to supply, methionine and cysteine. Gluten is very much an anti-nutrient once one is sensitive to it.
Recommended reading:
On gluten: Dangerous Grains by James Braly M.D. and Ron Hoggan M.A.
On milk, exorphins, and beta-casomorphin-7 (BCM7): The Devil in the Milk by Keith Woodford
On endorphin receptors and AIDS: Molecules of Emotion by Candace B. Pert
Ron Hoggan’s gluten research http://www.gluten-free.org/hoggan/
A readable introduction to gluten diseases (especially chapter 3) which discusses many syndromes also seen in Hep C http://www.gluten-free.org/hoggan/adhd.txt
Man the Hunter: An Essay on the Paleolithic Diet by Drs Mike and Mary Eades, http://www.ofspirit.com/tw-theproteinpowerlifeplan.htm (Highly recommended, as are all the Eade’s writings, and their Protein Power Blog).
from: Gluten is a Dangerous Luxury of Non-Celiacs http://www.gluten-free.org/hoggan/dubious.txt We hear all the time about pollution in the industrial world being the source for modern man's high incidence of cancer. It is the chemical additives, we are told, in the food we eat, that causes much of the problem. Perhaps. I would like to suggest that the evidence from antiquity, the pattern of the spread of agriculture in Europe coinciding with the patterns of civilizatory illnesses, the levels of SBHG associated with wheat consumption, the high incidence of gliadin antibodies among those with neurological illnesses of unknown origin, the sensitivity to gluten among siblings of celiacs in spite of the absence of genetic indicators associated with celiac disease, and my own investigation of the literature regarding lymphoma, all point to the strong possibility that gluten is a dangerous substance to many more people than just celiacs. - Ron Hoggan, 1997
To which I might add: the parallel associations between gluten sensitivity and the various syndromes traditionally attributed to HCV infection all point to the even stronger possibility that gluten is a very dangerous luxury for people with hepatitis C.
Not everyone exposed to HCV develops a chronic infection. The rate of natural clearance is unknown, because most people are not aware they are infected until the condition becomes chronic. One known factor in chronic infection with viral hepatitis (A or B) is selenium deficiency in malnourished populations. Celiac disease, the most easily diagnosed form of gluten toxicity, is known to cause selenium deficiency in well-fed populations. Celiac also causes a general deficiency of many antioxidants, protein, and minerals and vitamins. There is a strong association between HCV and celiac disease in many populations tested. There is an even stronger association between interferon-alpha treatment and celiac disease. Interferon-alpha is the cytokine that triggers celiac disease naturally. Celiac disease is only the easiest to diagnose of the gluten sensitivity syndromes. It results in destruction of the intestinal cell vilii, damage which can be detected on biopsy. Even so celiac is seriously underdiagnosed. It is likely that anyone in New Zealand with the symptoms of celiac disease, who is HCV positive, will be told that their symptoms are due to hepatitis C. Testing for Celiac will happen slowly and most likely not at all, unless the patient insists, and testing for other forms of gluten sensitivity is unlikely.
Milder forms of gluten sensitivity might only disrupt those gut receptors responsible for functions such as immune regulation (especially endorphin receptors), mineral transport, or absorption of specific vitamins. Antibodies may form to the proline-rich gluten, gliadin and casein sequences released by peptide digestion which enter the bloodstream, which then attack the proline-rich collagenous tissues, promoting diseases such as liver fibrosis and rheumatoid arthritis. It so happens that the auto-immune symptoms associated with celiac and gluten sensitivity diseases, including liver and gall-bladder disease, and which usually resolve slowly on a strict gluten and dairy-free diet, are essentially identical to the various syndromes seen in chronic Hep C, especially during or after interferon-alpha treatment. Syndromes caused by gluten in celiac disease include: - fibrosis and cirrhosis of the liver - gall bladder obstruction - insulin resistance - thyroiditis - sicca syndrome (dry eyes and mouth) - vasculitis - brain fog (poor memory, confusion) - depression - fibromyalgia - fatigue - optic neuritis - deficiencies of selenium, magnesium, zinc, chromium - deficiencies of fat-soluble vitamins (A, D, E, K) - deficiency of those vitamins converted in the intestines (including folate, B6) - anaemia - thrombocytopenic purpurea (low platelets due to autoimmunity) - GI disturbance; diarrhea, steatorrhea These symptoms are aggravated by the nutrient deficiencies, especially antioxidant, magnesium, and chromium deficiencies, associated with gluten sensitivity. In fact, the symptoms of both Hep C and celiac disease are often partially, but significantly, relived by supplementation of these nutrients, especially when anti-inflammatory botanicals (curcumin, grape seed, ginkgo, milk thistle etc) are added.
Other treatments effective against Hep C have obvious links to gluten sensitivity; for example, low dose naltrexone may exert its beneficial effects on cancer, autoimmune disease, and viral immunity by repairing damage done to endorphin receptors by gluten and casein digests. Similarly, enzyme therapy for cancers may work by promoting the complete digestion of gluten and casein exorphins, and the ketogenic diet for cancer may work by eliminating grains and lowering insulin levels (and hence inflammation), rather than merely by depriving cancer cells of glucose. Exorphins are chemicals found in protein digests (the peptides produced by pepsin digestion of food proteins) which have an affinity for endorphin receptors. Endorphins are the messengers of emotion, and gluten sensitivity is very often found in schizophrenia, autism, ADHD, Aspergers, and the various mood disorders. However, the endorphin system also regulates the immune system, and defects of endorphins and endorphin receptors are associated with cancers and autoimmune disease, as well as AIDS. Endorphins also regulate gut motility; the well-known constipating effect of cheese is an opioid effect. Even people who have no gluten antibodies and no leaky gut (which allows gluten digests to enter the bloodstream in especially large doses) are influenced by the opioid effect of exorphins at the local, gut level.
Diagnosing non-celiac gluten and casein sensitivity without exclusion diets is difficult, if not impossible. Commonly in New Zealand a scratch test for gluten is the doctor’s first choice. This is worse than useless, because we are not talking about an allergy to gluten at all (though these do exist). When gluten, milk and maize are digested in the stomach (by pepsin and hydrochloric acid) a variety of peptides are released. The exact combination of peptides that might appear in the gut varies with the individual, the state of his digestion, and the strain of wheat, milk or maize consumed. Gliadomorphin is a characteristic wheat exorphin; beta-casomorphin-7 is thought to be the most toxic milk exorphin; and the maize exorphins have not yet been identified. Autoimmune reaction to antigenic peptides is not the only way in which exorphins can harm us, so the current insistence on immunological testing seems limited. Also, current tests do not include antibodies to every possible peptide digest of gluten; this would probably be impossible. Further, in many cases symptoms may be due not to gluten but to agglutinating lectins found in the germ, or to phytates withholding nutrients (minerals and vitamin D), or to some synergy of all 3 components.
Luckily, no-one needs to eat grains. Our ancestors got along in better health without them for millions of years. Grain consumption is a comparatively recent phenomenon in human history; very recent indeed in some cases; in Northern Europe and in colonized Oceania it is a habit of mere centuries, if that. In parts of the world where grain-eating goes back longest, for example the eastern Mediterranean, there is a higher rate of adaptation. This does not mean that individuals adapted to grains; individuals died young or became sterile if they lacked the more grain-adapted genes, in order that the race might adapt. But this still does not rule out the diseases of later life. Study of remains of grain-dependent societies, such as Rome and ancient Egypt, show that so-called “modern” diseases such as arthritis and cancer were prolific there. It is trendy to think that such disease results from technology; radiation, pesticides, food processing; and that it can be prevented with an organic vegetarian diet. The sad truth is that in most cases wheat and milk - even organic wheat and milk – products of the older agricultural revolution – are doing more harm than those traces of the modern industrial revolution that we cannot avoid. If our immune systems and our detox enzymes cannot cope with some new agricultural chemical, the most likely reason is the disruption they have received from the old agricultural chemicals – gluten and casein.
It was also agriculture, not food processing, that first placed man in a guilty relationship with his food. Pre-agricultural man killed to eat and took from the forest, and had rituals that made peace with the animals and the plants. He took from these bounteous gods, not from captive creatures. Agricultural man kills for money, pays others to kill for him, and burns down the forest to plant his cash crops. If this was original sin, then the wages of sin have indeed been death.
It is customary to blame lead piping for the decline of Rome. The Roman people were highly wheat-addicted; they would riot for bread; “Bread and Circuses” was the formula for keeping them happy; they were so addicted that the state found it more convenient to supply bread for free (like a methadone clinic for the opiate of the people). Today the state oversees the addition of gluten, milk and maize to an ever-widening range of foods, so that a mere bread shortage is not likely to cause withdrawals. This is probably not intentional; addicts tend to assume that everyone wants to share their habit. In the case of Rome, wheat and lead may have had a synergistic toxicity. Both lead poisoning and wheat consumption tend to reduce iron and zinc absorption. This is why celiac children are often of short stature. The Romans would have become increasingly incapable of sensible planning and come to lack the stern old Roman self-control. We know that a decreasing birthrate of “true born” Romans eventually led to the conscription of barbarian armies and the opening up of Roman citizenship. Today gluten, and the antioxidant deficiency it causes, is a major cause of infertility.
Research has been done into the links between gluten sensitivity and Hep C, showing a strong association (especially after interferon therapy). There is also a strong association between Hep C and lymphoma (a cancer of the lymph glands). Lymphoma is the characteristic cancer caused by gluten; celiacs have a 30x elevated risk of lymphoma. To date no-one seems to have tested a strict gluten- and dairy-free diet for chronic Hep C or post-interferon toxicity, but a great many people with Hep C who take their health seriously have gone gluten free, often without knowing of the links between the two conditions, but motivated by their own well-being when avoiding gluten.
There is no nutritional need that can only be met by grains; nuts and seeds, for example, supply the same amino acids, fats and vitamins in greater concentration (for example, sunflower and sesame seeds are superior sources of methionine and vitamin E), while legumes are rich in complex carbohydrates. Gluten is also a cause of insulin resistance, and everyone who develops liver fibrosis has some degree of insulin resistance. Gluten itself causes a four-fold rise in insulin levels (unusual for a protein). The cure for insulin resistance is two-fold; a high-protein, low-carb diet (the Paleolithic diet is the most natural version of this diet) and replacement of the nutrients depleted by gluten which are essential for the function of insulin receptors; chromium, magnesium and the antioxidant minerals and vitamins. Gluten also seems to cause amino acid deficiencies, including some of the very amino acids which wheat is supposed to supply, methionine and cysteine. Gluten is very much an anti-nutrient once one is sensitive to it.
Recommended reading:
On gluten: Dangerous Grains by James Braly M.D. and Ron Hoggan M.A.
On milk, exorphins, and beta-casomorphin-7 (BCM7): The Devil in the Milk by Keith Woodford
On endorphin receptors and AIDS: Molecules of Emotion by Candace B. Pert
Ron Hoggan’s gluten research http://www.gluten-free.org/hoggan/
A readable introduction to gluten diseases (especially chapter 3) which discusses many syndromes also seen in Hep C http://www.gluten-free.org/hoggan/adhd.txt
Man the Hunter: An Essay on the Paleolithic Diet by Drs Mike and Mary Eades, http://www.ofspirit.com/tw-theproteinpowerlifeplan.htm (Highly recommended, as are all the Eade’s writings, and their Protein Power Blog).
from: Gluten is a Dangerous Luxury of Non-Celiacs http://www.gluten-free.org/hoggan/dubious.txt We hear all the time about pollution in the industrial world being the source for modern man's high incidence of cancer. It is the chemical additives, we are told, in the food we eat, that causes much of the problem. Perhaps. I would like to suggest that the evidence from antiquity, the pattern of the spread of agriculture in Europe coinciding with the patterns of civilizatory illnesses, the levels of SBHG associated with wheat consumption, the high incidence of gliadin antibodies among those with neurological illnesses of unknown origin, the sensitivity to gluten among siblings of celiacs in spite of the absence of genetic indicators associated with celiac disease, and my own investigation of the literature regarding lymphoma, all point to the strong possibility that gluten is a dangerous substance to many more people than just celiacs. - Ron Hoggan, 1997
To which I might add: the parallel associations between gluten sensitivity and the various syndromes traditionally attributed to HCV infection all point to the even stronger possibility that gluten is a very dangerous luxury for people with hepatitis C.
How a High-fat Paleo diet Protects against HCV replication and Fibrosis of the liver
The Hepatitis C virus replicates and infects cells by hijacking at least two cellular mechanisms, one of which is specific to liver cells; the RNA replication apparatus, which is essential in all cells (and thus is not a realistic target for nutritional therapy), and the mechanism which converts excess carbohydrate to triglycerides (fatty acids) and sends them to the blood stream to be stored in fat cells for later use.
The latter mechanism is largely optional, and is sent into overdrive by the high carbohydrate of the current, fashionable, “healthy” diet.
The human body has evolved to function on minimal or no carbohydrates, because we evolved under conditions, before the invention of agriculture, where game animals, birds, and fish were plentiful and most available plant sources of nutrition were relatively low in carbohydrates and rich in polyphenols and fibre (bitter or tart, and stringy) compared to those we eat today.
DGAT1 is a liver enzyme essential for HCV replication the production of which is triggered by insulin, which is the hormone the body produces in reaction to glucose, the digestion product of most carbohydrate foods, and more specifically in the liver by fructose, derived from sugar (sucrose) and fruit juice. Blocking DGAT1 is considered to be a realistic target of drug therapies for HCV. However, it is doubtful that any drug it is possible to invent could lower the level of DGAT1 as completely as a diet with no use for it; that is to say, a diet with minimal fructose and no more carbohydrate than can be burned for energy immediately (a very small amount unless you are an athlete in the middle of performance), or could lower DGAT1 without other unwanted effects. Once replicated, HCV escapes from infected hepatocytes via the membrane sites that release VLDL-"cholesterol" into the bloodstream. VLDL carries the triglycerides which have been formed to store the energy from excess carbohydrate (once these are dumped into fat storage VLDL becomes the notorious LDL. The more triglycerides packed into the original VLDL, the more harmful the type of LDL). HCV enters and infects new cells in tandem with LDL, using the LDL receptor. If you use oil or spreads high in "heart healthy" PUFA, including fish oil, the cells express more LDL receptors to pull more LDL from the blood. People with Hep C actually do better if their LDL levels are higher. PUFAs create an increased need for cholesterol; the cell membranes become sloppier and need more cholesterol reinforcement. Liver production of cholesterol, and total body cholesterol content, actually increases on a diet high in PUFA, while the blood level (serum cholesterol) is lowered.
The virus seeks to monopolize cholesterol production in order to reduce serum cholesterol and LDL; low cholesterol and LDL has the effect of increasing LDL receptors; the increased availability of receptors in a low-cholesterol environment maximizes HCV's access to naive cells via its own association with LDL.
Consuming cholesterol-rich foods in the diet also has the effect of reducing LDL receptors, especially in the context of a low-carbohydrate diet, and also reduces hepatic activity of HMG-Co reductase, an enzyme that may be essential in the early stages of HCV infection, and which remains in use by genotype 3.
Thus restricting fructose, total carbohydrate, and PUFA* and eating a cholesterol-rich diet produces three effects on HCV; 1) replication is slowed because less DGAT1 (and less HMG-CoA reductase) is expressed, 2) serum HCV level is lowered because less of the HCV is being secreted from infected hepatocytes. 3) less HCV is being taken up into uninfected hepatocytes. A further benefit is the improved immune function seen on low carb diets, as high insulin and glucose levels compromise immunity. The decreased expression of HCV core proteins also improves immunity, liver function and antioxidant status. Fibrosis is also heavily driven by insulin and all inflammatory processes are slowed or stopped by the serious reduction of carbohydrates. Eating a low carb diet means eating more fats and protein, and these have positive benefits for liver health; protein is a mixture of amino acids, almost all of which have been shown to have anti-inflammatory or antioxidant effects at the concentrations in a high-protein diet, and none of which are harmful (there is no evidence that high protein intake harms the kidneys; the sole experimental finding that began this myth resulted from feeding a diet of meat and soy protein to caged rabbits, an animal which naturally eats very little protein in its diet. If you feed a carnivorous or omnivorous animal a higher-protein diet its kidneys will, if anything, function better than they did before). As for fats, we have been lied to for years ("A lie can travel halfway round the world while the truth is still putting on its shoes" - Mark Twain). Saturated fats do not cause disease, and polyunsaturated fats are not necessarily healthy. A diet including beef tallow, the most saturated of animal fats, protects the liver of rats force-fed alcohol, and such diets are at the heart of the so-called French paradox; populations that drink heavily and eat most saturated fat have the lowest levels of heart disease and cirrhosis. We do not need to invoke resveratrol to explain this result.
(* PUFAs arachadonic acid, EPA, and DHA have antiviral effects on HCV replication, but are profibrotic at higher intakes.)
Dietary Saturated Fatty Acids Reverse Inflammatory and Fibrotic Changes in Rat Liver Despite Continued Ethanol Administration Amin A. Nanji1, Kalle Jokelainen2, George L. Tipoe3, Amir Rahemtulla4 and Andrew J. Dannenberg5 ananji@pathology.hku.hk http://jpet.aspetjournals.org/content/299/2/638.long
Abstract
We investigated the potential of dietary saturated fatty acids to reverse alcoholic liver injury despite continued administration of alcohol. Five groups (six rats/group) of male Wistar rats were studied. Rats in groups 1 and 2 were fed a fish oil-ethanol diet for 8 and 6 weeks, respectively. Rats in groups 3 and 4 were fed fish oil and ethanol for 6 weeks before being switched to isocaloric diets containing ethanol with palm oil (group 3) or medium-chain triglycerides (MCTs, group 4) for 2 weeks. Rats in group 5 were fed fish oil and dextrose for 8 weeks. Liver samples were analyzed for histopathology, lipid peroxidation, nuclear factor-κB (NF-κB) activation, and mRNAs for cyclooxygenase-2 (Cox-2) and tumor necrosis factor-α (TNF-α). Endotoxin in plasma was determined. The most severe inflammation and fibrosis were detected in groups 1 and 2, as were the highest levels of endotoxin, lipid peroxidation, activation of NF-κB, and mRNAs for Cox-2 and TNF-α. After the rats were switched to palm oil or MCT, there was marked histological improvement with decreased levels of endotoxin and lipid peroxidation, absence of NF-κB activation, and reduced expression of TNF-α and Cox-2. A diet enriched in saturated fatty acids effectively reverses alcohol-induced necrosis, inflammation, and fibrosis despite continued alcohol consumption. The therapeutic effects of saturated fatty acids may be explained, at least in part, by reduced endotoxemia and lipid peroxidation, which in turn result in decreased activation of NF-κB and reduced levels of TNF-α and Cox-2. Long-term treatment of alcoholic liver disease continues to incorporate vitamins, nutrients, and trace elements (Fulton and McCullough, 1998; McCullough et al., 1998). In fact, the role of specific pharmacological agents remains unproven. Clearly, the development of more effective nutritional or pharmacological therapy will depend on further elucidating the mechanisms that contribute to liver injury. Several lines of investigation indicate that dietary fat can modulate the severity of alcoholic liver injury (Mezey, 1998). In experimental animals, for example, diets enriched with saturated fatty acids protect against alcohol-induced liver injury, whereas diets containing polyunsaturated fatty acids promote liver injury (Nanji and French, 1989; Nanji et al., 1989, 1994a). Saturated fatty acids have also been reported to reverse established alcoholic liver injury (Nanji et al., 1995, 1996, 1997b). Importantly, in previous studies, use of alcohol was discontinued at the time that dietary treatment was initiated. This model represented the alcoholic patient who stopped drinking at the time of hospitalization (French, 1995). Discontinuation of alcohol remains pivotal in the treatment of alcoholic liver disease. Although this goal can frequently be achieved in the short-term, the majority of patients resume alcohol consumption, often with sudden deterioration in liver disease (Pares et al., 1986). Hence, it is important to develop therapeutic strategies that simulate the clinical condition in which alcohol use is continued despite the presence of alcoholic liver disease. Previously, we used the intragastric feeding rat model to study the pathogenesis of alcoholic liver disease (Nanji et al., 1999). In addition to being useful for elucidating mechanisms of injury, this model has been used to evaluate various strategies to prevent or reverse alcoholic liver disease (Nanji et al., 1995, 1997b). The results of previous studies suggest that elevated levels of endotoxin and lipid peroxides in alcohol-fed animals activate nuclear factor-κB (NF-κB), leading to enhanced expression of tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (Cox-2), and proinflammatory cytokines (Nanji et al., 1997a, 1999). In the current study, we investigated whether treatment with dietary saturated fatty acids could reverse established alcoholic liver injury despite continued administration of ethanol. We show that diets enriched in saturated fatty acids improved both histological liver injury and biochemical parameters that have been etiologically linked to liver injury.
(The ferretin levels in the livers of the saturated-fat rats were less than half those of the polyunsaturated fat-rats).
Beef Fat Prevents Alcoholic Liver Disease in the Rat Amin A. Nanji MD, FRCP(C), Charles L.
The amount and type of dietary fat is thought to be important in the pathogenesis of alcoholic liver disease (ALD). We investigated the role of different dietary fats in our rat model for ALD. Liver pathology was evaluated in rats fed ethanol and lard or tallow or corn oil over a period of 2 to 6 months. All experimental animals were pair-fed the same diet as controls except that glucose was isocalorically replaced by ethanol. Rats fed tallow and ethanol developed none of the features of ALD, those fed lard and ethanol developed minimal to moderate disease, rats fed corn oil and ethanol developed the most severe pathology. The degree of histopathological abnormality correlated with the linoleic acid content of fat in the diet (tallow 0.7%, lard 2.5%, corn oil 56.6%). We postulate that linoleic acid facilitates development of ALD and provides an explanation for our previous epidemiological observations. Effect of Dietary Fat on Ito Cell Activation by Chronic Ethanol Intake: A Long-Term Serial Morphometric Study on Alcohol-Fed and Control Rats Hisao Takahashi, Kim Wong, Linda Jui, Amin A. Nanji, Charles S. Mendenhall, Samuel W. French (note: Ito Cells are Hepatic Stellate cells in their normal state. This study is saying that rats fed beef tallow had no loss of Ito cells – that is, no conversion to myofibroblasts – whereas rats fed corn oil went into fibrosis) We studied the effects of long-term ethanol ingestion and dietary fat on Ito cell activation morphometrically in rats. Sixteen pairs of Wistar male rats were divided into two groups, one fed tallow and the other fed corn oil as the source of dietary fat. Each group of rats were pair-fed a nutritional adequate liquid diet containing either corn oil (CF) or tallow (TF) as fat as well as protein and carbohydrate. Half of each group received ethanol, the rest were pair-fed isocaloric amounts of dextrose via an implanted gastric tube for up to 5 months. Morphometric analysis of the change in fat and rough endoplasmic reticulum (RER) of Ito cells was performed on electron micrographs obtained from monthly biopsies including baseline. Ito cell activation was assessed by a decrease in the ratio of fat/RER in Ito cells. The ratio of fat/RER in Ito cells of alcoholic rats fed the CF diet (CFA) gradually decreased. The ratio war found to be lower than in the pair-fed control rats (CFC) at 5 months of feeding. CFA 1.74 ± 0.57, vs. 7.46 ± 2.05, respectlvely, p < 0.05, mean ± se). Ito cell fat also significantly decreased at 5 months of feeding (p < 0.05). The fat/ RER ratio In CFA significantly decreased only subsequent to the development of fatty change, necrosis, and inflammation followed by fibrosis of the liver. In contrast, the TFA rats did not show a significant decrease in the fat/RER ratio in the Ito cells throughout the study, while TFC rats showed an increase in the fat/RER ratio. Minimal pathological changes were observed in the livers of CFC, TFA, and TFC rats. These results indicate that activation of Ito cells at a significant level occurred only late in the course of feeding alcohol after moderate to severe abnormalities in liver histology had developed, although activation may have begun at an earlier time of ethanol feeding. The results indicate that dietary fatty acid composition may be an important factor in the pathogenesis of ethanol-induced Ito cell activation.
DGAT1 is a liver enzyme essential for HCV replication the production of which is triggered by insulin, which is the hormone the body produces in reaction to glucose, the digestion product of most carbohydrate foods, and more specifically in the liver by fructose, derived from sugar (sucrose) and fruit juice. Blocking DGAT1 is considered to be a realistic target of drug therapies for HCV. However, it is doubtful that any drug it is possible to invent could lower the level of DGAT1 as completely as a diet with no use for it; that is to say, a diet with minimal fructose and no more carbohydrate than can be burned for energy immediately (a very small amount unless you are an athlete in the middle of performance), or could lower DGAT1 without other unwanted effects. Once replicated, HCV escapes from infected hepatocytes via the membrane sites that release VLDL-"cholesterol" into the bloodstream. VLDL carries the triglycerides which have been formed to store the energy from excess carbohydrate (once these are dumped into fat storage VLDL becomes the notorious LDL. The more triglycerides packed into the original VLDL, the more harmful the type of LDL). HCV enters and infects new cells in tandem with LDL, using the LDL receptor. If you use oil or spreads high in "heart healthy" PUFA, including fish oil, the cells express more LDL receptors to pull more LDL from the blood. People with Hep C actually do better if their LDL levels are higher. PUFAs create an increased need for cholesterol; the cell membranes become sloppier and need more cholesterol reinforcement. Liver production of cholesterol, and total body cholesterol content, actually increases on a diet high in PUFA, while the blood level (serum cholesterol) is lowered.
The virus seeks to monopolize cholesterol production in order to reduce serum cholesterol and LDL; low cholesterol and LDL has the effect of increasing LDL receptors; the increased availability of receptors in a low-cholesterol environment maximizes HCV's access to naive cells via its own association with LDL.
Consuming cholesterol-rich foods in the diet also has the effect of reducing LDL receptors, especially in the context of a low-carbohydrate diet, and also reduces hepatic activity of HMG-Co reductase, an enzyme that may be essential in the early stages of HCV infection, and which remains in use by genotype 3.
Thus restricting fructose, total carbohydrate, and PUFA* and eating a cholesterol-rich diet produces three effects on HCV; 1) replication is slowed because less DGAT1 (and less HMG-CoA reductase) is expressed, 2) serum HCV level is lowered because less of the HCV is being secreted from infected hepatocytes. 3) less HCV is being taken up into uninfected hepatocytes. A further benefit is the improved immune function seen on low carb diets, as high insulin and glucose levels compromise immunity. The decreased expression of HCV core proteins also improves immunity, liver function and antioxidant status. Fibrosis is also heavily driven by insulin and all inflammatory processes are slowed or stopped by the serious reduction of carbohydrates. Eating a low carb diet means eating more fats and protein, and these have positive benefits for liver health; protein is a mixture of amino acids, almost all of which have been shown to have anti-inflammatory or antioxidant effects at the concentrations in a high-protein diet, and none of which are harmful (there is no evidence that high protein intake harms the kidneys; the sole experimental finding that began this myth resulted from feeding a diet of meat and soy protein to caged rabbits, an animal which naturally eats very little protein in its diet. If you feed a carnivorous or omnivorous animal a higher-protein diet its kidneys will, if anything, function better than they did before). As for fats, we have been lied to for years ("A lie can travel halfway round the world while the truth is still putting on its shoes" - Mark Twain). Saturated fats do not cause disease, and polyunsaturated fats are not necessarily healthy. A diet including beef tallow, the most saturated of animal fats, protects the liver of rats force-fed alcohol, and such diets are at the heart of the so-called French paradox; populations that drink heavily and eat most saturated fat have the lowest levels of heart disease and cirrhosis. We do not need to invoke resveratrol to explain this result.
(* PUFAs arachadonic acid, EPA, and DHA have antiviral effects on HCV replication, but are profibrotic at higher intakes.)
Dietary Saturated Fatty Acids Reverse Inflammatory and Fibrotic Changes in Rat Liver Despite Continued Ethanol Administration Amin A. Nanji1, Kalle Jokelainen2, George L. Tipoe3, Amir Rahemtulla4 and Andrew J. Dannenberg5 ananji@pathology.hku.hk http://jpet.aspetjournals.org/content/299/2/638.long
Abstract
We investigated the potential of dietary saturated fatty acids to reverse alcoholic liver injury despite continued administration of alcohol. Five groups (six rats/group) of male Wistar rats were studied. Rats in groups 1 and 2 were fed a fish oil-ethanol diet for 8 and 6 weeks, respectively. Rats in groups 3 and 4 were fed fish oil and ethanol for 6 weeks before being switched to isocaloric diets containing ethanol with palm oil (group 3) or medium-chain triglycerides (MCTs, group 4) for 2 weeks. Rats in group 5 were fed fish oil and dextrose for 8 weeks. Liver samples were analyzed for histopathology, lipid peroxidation, nuclear factor-κB (NF-κB) activation, and mRNAs for cyclooxygenase-2 (Cox-2) and tumor necrosis factor-α (TNF-α). Endotoxin in plasma was determined. The most severe inflammation and fibrosis were detected in groups 1 and 2, as were the highest levels of endotoxin, lipid peroxidation, activation of NF-κB, and mRNAs for Cox-2 and TNF-α. After the rats were switched to palm oil or MCT, there was marked histological improvement with decreased levels of endotoxin and lipid peroxidation, absence of NF-κB activation, and reduced expression of TNF-α and Cox-2. A diet enriched in saturated fatty acids effectively reverses alcohol-induced necrosis, inflammation, and fibrosis despite continued alcohol consumption. The therapeutic effects of saturated fatty acids may be explained, at least in part, by reduced endotoxemia and lipid peroxidation, which in turn result in decreased activation of NF-κB and reduced levels of TNF-α and Cox-2. Long-term treatment of alcoholic liver disease continues to incorporate vitamins, nutrients, and trace elements (Fulton and McCullough, 1998; McCullough et al., 1998). In fact, the role of specific pharmacological agents remains unproven. Clearly, the development of more effective nutritional or pharmacological therapy will depend on further elucidating the mechanisms that contribute to liver injury. Several lines of investigation indicate that dietary fat can modulate the severity of alcoholic liver injury (Mezey, 1998). In experimental animals, for example, diets enriched with saturated fatty acids protect against alcohol-induced liver injury, whereas diets containing polyunsaturated fatty acids promote liver injury (Nanji and French, 1989; Nanji et al., 1989, 1994a). Saturated fatty acids have also been reported to reverse established alcoholic liver injury (Nanji et al., 1995, 1996, 1997b). Importantly, in previous studies, use of alcohol was discontinued at the time that dietary treatment was initiated. This model represented the alcoholic patient who stopped drinking at the time of hospitalization (French, 1995). Discontinuation of alcohol remains pivotal in the treatment of alcoholic liver disease. Although this goal can frequently be achieved in the short-term, the majority of patients resume alcohol consumption, often with sudden deterioration in liver disease (Pares et al., 1986). Hence, it is important to develop therapeutic strategies that simulate the clinical condition in which alcohol use is continued despite the presence of alcoholic liver disease. Previously, we used the intragastric feeding rat model to study the pathogenesis of alcoholic liver disease (Nanji et al., 1999). In addition to being useful for elucidating mechanisms of injury, this model has been used to evaluate various strategies to prevent or reverse alcoholic liver disease (Nanji et al., 1995, 1997b). The results of previous studies suggest that elevated levels of endotoxin and lipid peroxides in alcohol-fed animals activate nuclear factor-κB (NF-κB), leading to enhanced expression of tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (Cox-2), and proinflammatory cytokines (Nanji et al., 1997a, 1999). In the current study, we investigated whether treatment with dietary saturated fatty acids could reverse established alcoholic liver injury despite continued administration of ethanol. We show that diets enriched in saturated fatty acids improved both histological liver injury and biochemical parameters that have been etiologically linked to liver injury.
(The ferretin levels in the livers of the saturated-fat rats were less than half those of the polyunsaturated fat-rats).
Beef Fat Prevents Alcoholic Liver Disease in the Rat Amin A. Nanji MD, FRCP(C), Charles L.
The amount and type of dietary fat is thought to be important in the pathogenesis of alcoholic liver disease (ALD). We investigated the role of different dietary fats in our rat model for ALD. Liver pathology was evaluated in rats fed ethanol and lard or tallow or corn oil over a period of 2 to 6 months. All experimental animals were pair-fed the same diet as controls except that glucose was isocalorically replaced by ethanol. Rats fed tallow and ethanol developed none of the features of ALD, those fed lard and ethanol developed minimal to moderate disease, rats fed corn oil and ethanol developed the most severe pathology. The degree of histopathological abnormality correlated with the linoleic acid content of fat in the diet (tallow 0.7%, lard 2.5%, corn oil 56.6%). We postulate that linoleic acid facilitates development of ALD and provides an explanation for our previous epidemiological observations. Effect of Dietary Fat on Ito Cell Activation by Chronic Ethanol Intake: A Long-Term Serial Morphometric Study on Alcohol-Fed and Control Rats Hisao Takahashi, Kim Wong, Linda Jui, Amin A. Nanji, Charles S. Mendenhall, Samuel W. French (note: Ito Cells are Hepatic Stellate cells in their normal state. This study is saying that rats fed beef tallow had no loss of Ito cells – that is, no conversion to myofibroblasts – whereas rats fed corn oil went into fibrosis) We studied the effects of long-term ethanol ingestion and dietary fat on Ito cell activation morphometrically in rats. Sixteen pairs of Wistar male rats were divided into two groups, one fed tallow and the other fed corn oil as the source of dietary fat. Each group of rats were pair-fed a nutritional adequate liquid diet containing either corn oil (CF) or tallow (TF) as fat as well as protein and carbohydrate. Half of each group received ethanol, the rest were pair-fed isocaloric amounts of dextrose via an implanted gastric tube for up to 5 months. Morphometric analysis of the change in fat and rough endoplasmic reticulum (RER) of Ito cells was performed on electron micrographs obtained from monthly biopsies including baseline. Ito cell activation was assessed by a decrease in the ratio of fat/RER in Ito cells. The ratio of fat/RER in Ito cells of alcoholic rats fed the CF diet (CFA) gradually decreased. The ratio war found to be lower than in the pair-fed control rats (CFC) at 5 months of feeding. CFA 1.74 ± 0.57, vs. 7.46 ± 2.05, respectlvely, p < 0.05, mean ± se). Ito cell fat also significantly decreased at 5 months of feeding (p < 0.05). The fat/ RER ratio In CFA significantly decreased only subsequent to the development of fatty change, necrosis, and inflammation followed by fibrosis of the liver. In contrast, the TFA rats did not show a significant decrease in the fat/RER ratio in the Ito cells throughout the study, while TFC rats showed an increase in the fat/RER ratio. Minimal pathological changes were observed in the livers of CFC, TFA, and TFC rats. These results indicate that activation of Ito cells at a significant level occurred only late in the course of feeding alcohol after moderate to severe abnormalities in liver histology had developed, although activation may have begun at an earlier time of ethanol feeding. The results indicate that dietary fatty acid composition may be an important factor in the pathogenesis of ethanol-induced Ito cell activation.
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