Omega-3 fish oils

Omega-3 oils can only lower inflammation if you remove omega-6 vegetable oils from your diet

Wikipedia has a good explanation of fats and fatty acids. What is important here is what fatty acids are (long chains of carbon atoms with a carboxyl group on the end; the shortest is acetic acid [vinegar] that has one carbon on the chain attached to the acid group), how they are present in your diet, how they get to your cells and how your cells convert the fatty acids into inflammatory or anti-inflammatory short-range hormones, prostaglandins.

Fatty acids differ by the length of their carbon chains (always even numbers, since they are synthesized by the addition of pairs of carbons), and the number and positions of unsaturations (two bonds between the same carbon). Chemists would normally number the carbon atoms from the starting acid, but in this case the distance from the other end is what is important, so a fatty acid with a double bond between the last 3rd and 4th carbons would be call an “omega-3” fatty acid. The two most important omega-3 fatty acids are EPA (20 carbons) and DHA (22 carbons). They are both present in fish oil.
DHA



EPA



Most plant sources of omega-3 fatty acids, e.g. flax (ALA, 18), are much less effective in anti-inflammation, because they are too short.
ALA



Leafy plant materials have some useful omega-3 fatty acids, but seeds tend to have omega-6 fatty acids. Most vegetable oils, with the very important exception of olive oil, promote inflammation. In this context, I think that saturated fats, e.g. eggs and butter, are safer for your health than common vegetable oils, such as corn oil. The increase in degenerative and autoimmune diseases in the last fifty years can be attributed to the shift from dietary saturated fats to unsaturated vegetable oils (and trans fats). In the absence of chronic inflammation, I don’t think that saturated fats will contribute to heart disease -- deposition of fats and cholesterol at sites of inflammation is the problem.

Fatty acids are present in your diet attached to a short three carbon compound, glycerol. The glycerol with three attached fatty acids is called a triglyceride or fat. The fatty acids (also called soap) can be removed from the fats by boiling in lye = saponification. That’s the source of high glycerine soap.

You can’t digest fats without the soapy contents of bile from your pancreas. So if you swallow a couple of fish oil capsules on an empty stomach, the oil will just keep moving through your intestines. You need to take fish oil with other fat-rich foods to get the maximum benefit.

Fatty acids are removed from fats in the intestines and after transport to the liver. They are then transported out to the cells of your body and converted into phospholipids, glycerol with two fatty acids and a phosphate instead of a third fatty acid. Cell membranes are made of phospholipids and cholesterol. The phospholipids with longer fatty acid chains, e.g. DHA, EPA, form into thicker islands in the membrane. The fatty acids from these islands are removed and converted by an enzyme, COX, into the prostaglandins. Omega-3 fatty acids are converted into anti-inflammatory prostaglandins by COX and they also block the production of inflammatory prostaglandins from omega-6 fatty acids. Omega-3 oils are only effective in lowering inflammation if omega-6 vegetable oils are eliminated, if enough is present continuously to block conversion of omega-6 fatty acids already present, and the fish oil is consumed with other fats that trigger bile production.

Aspirin binds to COX and inactivates it so that fewer prostaglandins of either type are made. Since inflammatory prostaglandins are needed to produce healthy gut tissue, aspirin can be hard on your stomach and intestines.

Prostaglandins are very important in many natural processes. Birth for example, results from an increase in inflammatory prostaglandins and labor can be stopped with aspirin.

Stored fat is a constant source of prostaglandins. Unfortunately, the omega-6 fatty acids already present in your stored fat will be competing with the omega-3 fish oils that you consume. If you already have lots of stored fat, i.e. obesity, then you cannot afford to have vegetable oil in your diet and 6-12 fish oil capsules eaten with meals will be required to see a reduction in inflammation. Exercise will be even more important.

The simple dietary requirements for the anti-inflammatory impact of fish oil are the reason why many omega-3 trials have been inconclusive. When properly administered, omega-3 oils have been effective in the treatment of allergies, Alzheimer’s, asthma, arthritis, atherosclerosis, ADHD (just to start with the “As”). Omega-3 oils can also reduce many problems of pregnancy, such as some forms of infertility (male and female), pre-eclampsia, autism and low birth weight (short gestation).

Eating Rules -- Omega-3

Fish oils are anti-inflammatory and are most effective when other vegetable oils are avoided, but are eaten in a meal in which other fats stimulate bile production.

Omega-3 fatty acid rules:

• Avoid vegetable oils in general -- corn is very bad, soy is bad and canola is not too bad
• Only olive oil is acceptable
• Flax oil is too short and still has omega-6 fatty acids -- most labeling is misleading
• Saturated fat in butter and eggs is ok and safer than vegetable oil
• More symptoms of inflammation means more fish oil supplements are needed
• Take fish oil supplements with meals and preferably fatty foods to stimulate bile

Explanation: The omega-3 fatty acids that count are those that are essential, i.e. the body can’t make them, EPA (C20) or DHA (C22), or that can be produced from ALA (C18). EPA and DHA can be converted into anti-inflammatory prostaglandins by COX, the enzyme that is blocked by aspirin. COX also converts omega-6 fatty acids into inflammatory prostaglandins. Unfortunately the corresponding short omega-6 fatty acids block the elongation of the short omega-3 ALA. For this reason, supplementing most vegetable oils, that are rich in omega-6 oils, with even high levels of omega-3 fatty acids, will still leave the vegetable oils inflammatory. In most cases the only alternatives are eating more fatty fish than you would normally eat or fish oil supplements.

Most people have found that without any symptoms of inflammation two gram capsules per day of combined EPA-DHA fish oil meet requirements for health. Two more capsules should be added per day for obesity and two more for other symptoms of inflammation, e.g. arthritis, allergy, etc. Spread the supplements over multiple meals. Eating the fish oil with other fat-rich food will improve absorbance in the gut by stimulating the release of bile -- capsules on their own will just slip on past. I would recommend an empirical approach -- start with two capsules a day and see if your symptoms lessen within a week. If not, increase by two more capsules a day and monitor your symptoms. The severity of your inflammatory inputs will determine how much fish oil is required. Other sources of omega-6 oils will sabotage the anti-inflammatory benefits of the omega-3 fatty acids supplements. Saturated fats and cholesterol are not as much of a problem as the omega-6 fatty acids (and of course trans fats.)

Obesity is a particular problem, because the fat is a source of omega-6 fatty acids that were eaten when your diet was worse. You will continue to pay for previous dietary errors. For this reason, a diet rich in olive oil is helpful, because fat stored from this oil will be low in omega-6 fatty acids that could be troublesome in the future. This may be a significant component of the benefit of the Mediterranean diet.

Osteoporosis Treatment

Osteoporosis is an imbalance between bone production and loss. Most loss is due to dietary use of omega-6 vegetable oils. Treatment should focus on elimination of demineralizing oils and minimizing inflammation.

It is hard for me to discuss osteoporosis without the image of Sally Field advocating the use of Boniva (the bisphosphonate Ibandronate, see figure) popping into my head. Advertising is very powerful. Bisphosphonates stop bone loss by killing osteoclasts, the cells that demineralize bone during bone remodeling.

Normally demineralization of bone by osteoclasts is followed by secretion of osteoid containing osteocalcin by osteoblasts. Osteocalcin initiates mineralization. Thus, a large fraction of bone is being rejuvenated by balanced osteoclast/osteoblast action at any given time. Cessation of this remodeling process in bone as in cartilage and other connective tissue, e.g. skin, gives the symptoms of aging.

Osteoporosis, loss of bone density, means that there is a net conversion of bone hydroxyapatite (calcium phosphate crystals) into blood calcium, followed by calcium loss in urine. This means that the continuing development and activity of osteoblasts and osteoclasts is out of control. Osteoblasts develop from stem cells that are also the origin of fat adipocytes. The transcription factor that controls the alternative destiny of these stem cells is PPARgamma. Omega-6 fatty acids are converted into molecules that stimulate PPARgamma and result in adipocyte production in bone marrow instead of osteoblasts. In general terms, vegetable oil (except olive oil) makes fat cells instead of bone cells.  This is particularly true in postmenopausal women.  It is no wonder that the emphasis on the use of vegetable oils to avoid saturated fats has resulted in a pandemic of osteoporosis.

Omega-3 fatty acids (fish oil) are anti-inflammatory and they do not stimulate the production of PPARgamma. As a consequence omega-3 fatty acids, DHA and EPA, enhance bone production and density, and are very important to maintain normal osteoblast production.

Osteoporosis treatments that block osteoclast development or activity can be expected to have long term side effects, because normal renewal of bone is being disrupted. Inhibiting bone demineralization can lead to a slowing of osteoporosis, but it does not get to the cause of the osteoporosis.

Because of the prevalence of diet-based chronic inflammation, one might expect that diet and lifestyle are also the foundation of most osteoporosis.  With both inflammation and osteoporosis vegetable oils appear to be the major culprit.  Aging is also associated with osteoporosis.  Most of the symptoms of aging can be attributed to mismanagement of chronic inflammation.  Now it turns out that osteoporosis is a dietary problem (vegetable oil) compounded by physical problems of inflammation that limit activity.  Loss of muscle mass, i.e. sarcopenia, and replacement with fat around organs and in bone marrow can be explained by diet-based chronic inflammation and inadequate weight-bearing exercise.

A major risk factor for osteoporosis is omega-6-rich vegetable oils, e.g. corn, soy, etc. In simple terms, the first step that I would recommend for anyone concerned about osteoporosis is to shift to an anti-inflammatory diet. Eliminate all vegetable oils, except olive oil, from the diet and supplement with omega-3 fish oils (short-chain omega-3 oils in most vegetable sources are much less effective.)

The biomedical literature is very clear. Osteoporosis is not normal, is not a part of aging and can be avoided. There are some genetic predispositions to osteoporosis, but most can be overcome by meaningful diet and lifestyle changes. An anti-inflammatory diet and lifestyle (sunlight for vitamin D and exercise) is the cheapest, safest and most effective way to prevent and treat osteoporosis.

American Heart Association OKs Linoleic Acid and Arachidonic Acid

Can the AHA be correct in promoting omega-6 PUFAs? Doesn't this conflict with the broad therapeutic action of omega-3 PUFAs, EPA/DHA, against inflammatory diseases?

The dietary shift from saturated animal fats to polyunsaturated fatty acids (PUFAs) from vegetable oils paralleled the shift from infectious diseases to inflammatory/degenerative diseases as predominant killers in the Western world. Treatments for degenerative diseases associated with aging have improved, but these diseases have become more prevalent and the age of onset has decreased. And medical costs have skyrocketed. Omega-6 vegetable oils seem to be the problem, but the American Heart Association (AHA) has recently given these PUFAs a clean bill of health.

Why the AHA Conclusions Seem Just Wrong

The rise of inflammatory/degenerative diseases follows the shift to processed foods rich in omega-6 PUFAs (corn, soy, cottonseed, safflower oils) and simple carbohydrates (grain starch, sugar, high fructose corn syrup), but the AHA presents scientific data to exonerate omega-6 PUFAs. The central problem is that the AHA’s conclusions are not based on a conceptual framework to explain cardiovascular disease. Instead, conclusions are derived from experiments in which various diets are fed to people and consequences are analyzed. With some diseases, in which there is a simpler cause and effect relationship, this approach might lead to useful answers, unfortunately, the inflammatory component central to cardiovascular disease can have multiple, alternative origins and simple experiments yield misleading conclusions.

Experimental Basis for AHA Support for Omega-6 PUFAs

• Conversion of short PUFAs found in the diet, e.g. LA, to the long PUFAs that serve as the precursors of cellular hormones. But conversion is thought to be inefficient, so that less than 1% conversion occurs and short PUFAs have little impact on cellular long PUFA concentrations. Moreover, the brain does not perform the conversion and the high brain content of DHA is supplied on demand from DHA circulating in the blood.
• There don’t appear to be any direct, inflammatory derivatives of LA (C-18), but after it is converted to AA (C-20), the arachidonic acid is the starting point for the conversion to most of the inflammatory and anti-inflammatory cellular hormones, e.g. prostaglandins, leukotrienes and lipoxins. Thus inflammation is initiated by AA-derived products, but resolution and return to normal physiology is also based on other AA-derived products.
• Increases in blood plasma AA are associated with anti-inflammation, not inflammation.
• Increases in dietary AA and/or LA result in a decrease in cardiovascular disease. Replacing dietary saturated fat with PUFA leads to a reduction of disease by 25-50%. Higher serum LA translates into less disease.
• Increases in dietary LA result in lower serum cholesterol and LDL, but paradoxically they also lead to a narrowing of arteries.
• The relative amounts of dietary PUFAs (USA) are LA 15grams/day, AA 0.15g/d, ALA (omega-3, C-18, linolenic acid) 1g/d, EPA/DHA <>

Statins Lower Cardiovascular Disease by Lowering Inflammation (LDL Not Important)

The JUPITER study showed that the statin Crestor was effective in lowering heart disease, because it lowered inflammation. Individuals with chronic inflammation responded to Crestor by lowering inflammation. Lowering of LDL levels, however, was not related to decreasing disease. Elevated LDL levels may reflect inflammation.

Relating the JUPITER results to the AHA conclusions suggests that LA and AA may reduce inflammation and as a consequence also reduce serum LDL.

Inflammation Is the Cellular and Tissue Response to Many Stresses

The list of pathogens that trigger inflammation is long and includes specific signals from viruses, bacteria, fungi and protozoa. Pathogen-caused damage, as well as physical trauma, cause inflammation. Disruption of cellular metabolism and energy flow by vitamin, mineral, amino acid, or fatty acid deficiencies or excesses all produce inflammation. One of the difficulties of diagnosis is the overlapping of symptoms originating from numerous sources of underlying inflammation. Herniation of vertebral disks, for example, can be triggered by physical trauma, but it also may be initiated by the intestinal inflammation of gluten-based celiac. Acne and depression are common symptoms of chronic inflammation that may result from dietary deficiencies, gum disease, gluten sensitivity, etc. All of these examples respond to anti-inflammatory diets.

It is difficult to identify the sources of inflammation in experimental studies. In cardiovascular disease, the sources of inflammation are commonly not known in individual cases and the cardiac symptoms are treated. In reality, these are actually many different diseases, all with different sources of inflammation, pigeon-holed under the same symptom, a cardiac event. The most effective long term treatment for the dispart group is general suppression of inflammation. Any specific treatment of a root cause only works on a small subset of the group and would be considered ineffective. Thus, statins are considered effective against heart disease, because they reduce inflammation that is common to the whole group. Reduction of LDL is inadvertently used as a measure of control of inflammation and has become inappropriately designated as a risk factor. Directly lowering LDL has no impact on heart disease, but it is easy to measure. Inflammation is hard to measure and finding the source of inflammation is harder still.

Omega-6 Vs. Omega-3 Is Another False Dichotomy

Just as there is no opposite to inflammation, omega-6 and omega-3 fatty acids are not in opposition. The action of aspirin is the big clue. Aspirin changes the structures of the enzymes involved in converting AA into inflammatory prostaglandins and leukotrienes, with the result that anti-inflammatory lipoxins are produced instead. Aspirin is a biochemical switch that mimics the natural transition of the cellular machinery from producing enzymes that accentuate inflammation, to enzymes and signals that are the next step in the cycle, repair and restoration of normalcy.

Omega-6 PUFAs are needed for both inflammation and restoration of normal cellular functions. Some of the enzymes produced during inflammation are needed for the reset to normalcy. The difficulty comes when inflammation is sustained, components are depleted and the cycle cannot be completed. The result then is chronic inflammation, the symptoms of metabolic syndrome and degenerative diseases.

Why Did Demonizing LA and AA Seem Right?

It seems wise not to trust medicine, dietitians and the food industry, because they have made so many lamentable mistakes making dietary suggestions that have shortened so many lives. Professional societies like the AHA also frequently give silly advice, because the advice doesn’t reflect the best information from the biomedical literature. So it makes sense to be skeptical.

In this case the AHA appears to be right, only because established views were supported by straightforward experiments. What determines if an excess of dietary LA and AA is going to be a problem with inflammation is the absolute amount of AA and EPA available on the surface of immune cells. PUFAs are attached as part of the phospholipids of the lipid rafts on the membrane surface of immune cells that have received a inflammatory signal, e.g. bacterial lipopolysaccharide. There is usually adequate AA to be converted by enzymes on the cell surface to produce further inflammatory signals. The problem comes if there is so much AA that the EPA never made it to the lipid rafts. The result would be inadequate EPA conversion to anti-inflammatory prostaglandins and failure to return to normalcy. This would be a particular weakness in the presence of a large depletion of the EPA pools during sustained inflammation and chronic inflammation would result.

Thus, the AHA promotion of omega-6 PUFAs is half right. They should have said that omega-6 fatty acids are not a problem, if there is adequate EPA/DHA and no sustained inflammation. Unfortunately, the Western diet provides inadequate EPA/DHA and deficiencies that constantly produce inflammation. Of course, those enjoying an anti-inflammatory diet and lifestyle have biochemical tolerance for the AHA’s suggestions. Others eat vegetable oils at their peril.

reference:

Harris WS, Mozaffarian D, Rimm E, Kris-Etherton P, Rudel LL, Appel LJ, Engler MM, Engler MB, Sacks F. 2009. Omega-6 Fatty Acids and Risk for Cardiovascular Disease. A Science Advisory From the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention. Circulation. 2009 Jan 26. [Epub ahead of print]

Anti-inflammatory, Gluten-Free Diet for Celiac

Low Grain Is Good for Everyone

I don’t think that I have an intolerance for grain, i.e. a gluten sensitivity, but it is so common and the biochemistry is so obvious, that it is only prudent to avoid wheat and related grain products. A low or gluten-free diet is also similar to the other common healthy diets, e.g. low carb and anti-inflammatory.

Gluten-free diets came to my attention recently in two ways. First, I saw Food, Inc., a documentary movie about abuses by multinational food processors. After that movie, I felt like I was a goose being readied for foie gras. Second, was a newspaper article on the expense of a gluten-free diet and the challenges of avoiding gluten.

I haven’t had to worry about wheat contaminating my diet, but I am sympathetic to the celiacs that I know who have to labor with a sloppy and exploitative food industry that uses the cheapest ingredients to compose the processed foods that are consumed in modern diets -- processed foods are complex blends of many different potential allergens from innumerable sources throughout the world.

A Celiac Diet Is Good for All
Fortunately, the answer to pervasive gluten is just a modest modification of the basic anti-inflammatory diet that I recommend on this blog. Unfortunately, people who have already developed gluten intolerance, have probably had the problem for years before diagnosis and that means that their intestines have already suffered major physiological alterations and they have problems absorbing nutrients and vitamins. Celiacs also, because of their chronic inflammation and autoimmunity, tend to readily develop food allergies and other autoimmune diseases. The recommended anti-inflammatory diet will help to avoid celiac, put celiacs into remission and avoid development of subsequent allergies and autoimmune diseases.

Vitamin D Is Usually Deficient (and a source of inflammation)
The basic anti-inflammatory diet starts with a return to optimal vitamin D with the use of an initial blood test, followed by high level supplements to reach a suitable level and then maintenance with D3 supplements of usually 2,000-5,000 IU per day. Depending on the D3 supplement, vitamin A will also need to be supplemented, because it interacts with vitamin D. Remember that sunshine is only effective in producing adequate vitamin D if you do not suffer from chronic inflammation. I would assume that all celiacs tend to be vitamin D deficient.

A Low Carb Diet Is Easier for Celiacs
The next component of the basic diet is low carbohydrates, that means a minimum of high glycemic foods, which means to avoid sugar and starch, do not cook vegetables more than necessary and don’t over-chew your veggies. This is good for celiacs, because it reduces the need for common grain foods that no one should eat: bread, cereal, pasta, etc. Everyone should lower their consumption of these wheat products in solidarity for celiacs and for general good health. Cereal is a very bad idea for children!

Most Vegetable Oils Are Unhealthy
Most vegetable oils contribute substantially to world-wide inflammation and celiacs don’t need the added burden of inflammatory omega-6 vegetable oils. Only olive oil and butter should be used. Saturated fats are safer than typical polyunsaturated vegetable oils.

Eat Wild Fish or Tons of Fresh Flax
Most people eat too little omega-3 long chain fatty acids, since these are most abundant in fatty fish, such as wild salmon (farmed fish are fed corn and have reduced omega-3 and increased omega-6 fats.) Few vegetable sources are available, since the omega-3 fatty acids are unstable and present in leaves rather than seeds. Flax seeds have short chain omega-3 fatty acids and must be freshly ground and consumed by the cupful, because the conversion to the long chains, in which they are useful, is very inefficient. Most celiacs will need to use fish oil (or krill oil, if fish is not tolerated) supplements (4-8 EPA/DHA capsule per day taken in a meal rich in fats for bile uptake) to balance the ubiquitous inflammatory omega-6 in their diets.

Grassfed Meat/Eggs Are Your Friends
Celiacs should seek out grass/pasture fed meats, eggs and wild caught fish. Corn-fed animals have higher levels of omega-6 fats and these contribute to dietary inflammation. Celiacs can usually eat meat and fish and these are very healthy foods. Red meat was not shown to contribute to degenerative diseases, it was the high carbs eaten with the meat that produced the inflammation that contributed to heart disease. (Remember that statins only decrease cardiovascular disease because they inadvertently lower inflammation, not because they lower serum lipids, LDL.)

No, No’s: HFCS and trans fats
High fructose corn syrup and trans fats are inflammatory and unhealthy for anyone, and should be avoided as much as wheat gluten. Fruits should be eaten as seasoning, since their fructose is not healthy and they also contain ample sucrose.

Most People Would Be Healthier on a Celiac Diet
The anti-inflammatory diet proposed here for celiacs should be uniformly healthy, since it provides optimal vitamins (D, C, B12, etc.), low starch/sugar/carbs, an optimal omega-3 to -6 fatty acid ratio, increased meat and saturated fats, and avoids HFCS and trans fats. The only major adjustment for celiacs would be avoidance of individual food allergens, more attention to vitamin supplements to compensate for poor absorption and replacement of wheat by rice, potatoes, etc. The low carbohydrate nature of the diet makes it more approachable, since typical carbs, such as bread and cereal are avoided and replaced with meat and vegetables.

I look forward to advice and suggestions from readers who have experience with gluten-free diets.

Omega-3 Fatty Acids, Antioxidants and Cancer

It is hard to sort out the inflammatory effects of short/long-chain omega-6 and omega-3 fatty acids. Vegetable antioxidants make the picture even worse. The absolute, as well as relative amounts, of the various types of fatty acids make a difference. It also now appears that oxidation prior and during digestion may be important to the impact of polyunsaturated fatty acids (PUFAs). The source (perhaps even the meal composition) of the PUFAs was as important as omega-3 versus omega-6, for common, short chain PUFAs.

In some studies, omega-3 PUFAs, such as the short-chain alpha linolenic acid (ALA) common in flax seed or the long-chain fish oil FUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduced cancer in human and mice. Earlier work in cell cultures showed that all of PUFAs suppressed the growth of cancer cells.

A large French study (reference below) began in 1993. Approximately 100,000 women between the ages of 40 and 65 volunteered to provide dietary and breast malignancy information and ca. 75,000 qualified for the study (the French component of EPIC, European Investigation of Cancer and Nutrition) . The dietary data provided information on the fatty acid composition of meals and revealed who was eating vegetable antioxidants and vitamins.

Major findings:

• Neither omega-6 nor omega-3 fatty acids were related directly to breast cancer risk.
• Long chain omega-3 fatty acids (EPA and DHA) reduced breast cancer in the group of women with the highest consumption of omega-6 PUFAs.
• High LA or ALA consumption in the form of vegetable oils or vegetables reduced cancer incidence.
• High LA or ALA consumption in the form of processed foods or nuts was associated with a higher incidence of breast cancer.
• Longer chain PUFAs were not associated with increased risk, regardless of source.

What does this mean?

• The source of the PUFA is of paramount importance. This study may apply more specifically to cancers and less to other inflammation-based degenerative diseases. The general anti-inflammatory diet may need refinement. I would suggest the following additions:
• Retain the preference for the more omega-3 friendly olive oil or perhaps flax oil versus the omega-6 rich vegetable oils (corn, soy, safflower), but focus on freshness and do not heat these oils.
• The data seem to be in favor of saturated fats for cooking. That means a shift to coconut oil.
• Vegetable antioxidants may be most important in the gut during digestion. Do these antioxidants even enter the blood stream? Certainly some alkaloids get to the brain, but much of the impact of the less mobile, large molecules may be restricted to the gut.
• An extension of this discussion may be to encourage eating more leafy vegetables with meat. That may be the paleo-diet connection.

reference:
Thiébaut AC, Chajès V, Gerber M, Boutron-Ruault MC, Joulin V, Lenoir G, Berrino F, Riboli E, Bénichou J, Clavel-Chapelon F. 2009. Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer. Int J Cancer. Feb 15;124(4):924-31.

Depression

Your Diet is Depressing

It is no wonder that Americans are depressed. Workers are depressed. College students are depressed. Kids are depressed. New mothers are depressed. And they are all medicated with ineffective anti-depressants. It is an increasing epidemic of poor mental health care.

What is not uniformly recognized is that depression is a symptom of chronic inflammation. Moreover, the same diet changes that help with other degenerative and autoimmune diseases, also help with depression. There was a recent research article that found that postpartum depression in new mothers responded to anti-inflammatory drugs.

I am, of course, dealing in sweeping generalizations here and I explicitly am not attempting to replace medical evaluation in particular cases. There are many different kinds of depression. I just think that the impact of diet on mental health is depressingly ignored.

An evaluation of more than 250 studies on the usefulness of omega-3 oils in the treatment of many different mental health problems, including depression, observed conflicting results. One of the major problems with the studies, was that the researchers did not control the amount of omega-6 oils in the diets of the participants. Since it is the ratio of omega-3 to omega-6 oils in the diet that is important in controlling inflammation, this is a shocking mistake. The researchers seem to have been assuming that the omega-3 oils were treating a deficiency, instead of inhibiting the production of inflammatory prostaglandins from the omega-6 oils.
I think that most of the public dietary guidelines get it wrong, because they focus on reducing saturated fats. Replacing saturated fats with omega-6 unsaturated fats, e.g. corn oil, will lead to chronic inflammation. I don’t think that there is any good research that shows that there are health risks for saturated fats in your diet, unless you are in a chronic inflammatory state -- if you already exhibit the metabolic syndrome, then saturated fats are a double whammy.

It would seem obvious that anyone seeing a physician for depression, should be advised to shift to an anti-inflammatory diet. I think that the shift in diet will have greater impact than antidepressants. The first step is to ban trans-fats, high fructose corn syrup and omega-6 rich vegetable oils from the kitchen. Try to only use olive oil. The second step is to increase omega-3 oils by eating fatty fish and supplementing with fish oil capsules. I recommend an experiment to gradually increase omega-3 oils in your diet until you see relief from your depression. Each week keep track of how you feel each day. Starting with four fish oil capsules per day, increase each week by two more capsules per day, e.g. week 1 - 4 caps, week 2 - 6 caps, week 3 - 8 caps. The upper limit is probably about 12 caps/day. It will be harder if you are obese, because fat cells are inflammatory. Digestion of the oil is improved when eaten with other fat-rich foods. The capsules can be spread over several meals.

The bottom line: depression can result from chronic inflammation that has spilled over to become inflammation of the brain. Treating the chronic inflammation by correcting diet should reduce the symptoms of depression. It has been my observation that depressed people seem to benefit from gaining control of some part of their lives, so changing diet may be a good place to start.

Osteopetrosis

Bones like stones, that is osteo-petrosis. It is the opposite of osteoporosis, porous bones. Osteopetrosis is a disruption of bone metabolism so that mineralization by osteoblasts predominates over demineralization by osteoclasts.

Mice lacking almost all genes, i.e. knockout mice, are now available. To determine which body tissues require the inflammatory transcription factor, NFkB, NFkB knockout mice were engineered and their characteristics were carefully analyzed. Their bones kept mineralizing and mineralizing and mineralizing. NFkB function was required for the development and function of osteoclasts, the macrophage-derived cells that remove bone.

Inactivation of osteoclasts or inhibition of osteoclast development by bisphenols, such as Boniva, leads to a minor version of osteopetrosis. Killing osteoclasts leads to a reversal of osteoperosis. An omega-3 fatty acid deficient diet leads to osteoporosis in mice.

Omega-3 fish oil has been used to reduce inflammation induced bone loss associated with many diseases, e.g. arthritis, periodontitis and osteoporosis. In a recent study (below) the fish oils, DHA and EPA were added to mouse macrophages in culture and the impact on differentiation into osteoclasts was analyzed. DHA was more effective than EPA in reducing NFkB activation and TFA response leading to macrophage differentiation. The omega-6 fatty acid, ALA, enhanced osteoclast differentiation, consistent with many animal and human studies that show that the high omega-6 fatty acid content of such common vegetable oils as corn, soybean and safflower, are inflammatory and presumably encourage osteoporosis.

Osteoporosis increase in our population has paralleled the increase in use of omega-6 vegetable oils, and the increase in chronic inflammation. The first step in treating osteoporosis should be a shift to an anti-inflammatory diet lacking these vegetable oils. Olive oil is much safer.


Rahman MM, Bhattacharya A, Fernandes G. 2008. Docosahexaenoic acid is more potent inhibitor of osteoclast differentiation in RAW 264.7 cells than eicosapentaenoic acid. J Cell Physiol. 214:201-9.

Medical Advice Is Just Wrong

Medical advise says to avoid sun, fats and red meat, but to drink lots of water, eat polyunsaturated vegetable oils and focus on the grain-rich bottom of the food pyramid. The medical advice is simply wrong and is not supported by the biomedical literature. A recent article in a major medical journal claims that about 90% of medical advice is not based on clinical research studies, but rather represents the opinions of experts who are supported by the health industry. Most research is conducted to support products. Unfortunately the advice that comes from medical societies is not healthy.

Here I will provide a few examples to illustrate that medical advice is frequently, if not usually, wrong about diet, nutrition, cause of disease, appropriate drug use and whether to spend a few unprotected moments basking in sunshine.

The Sun Is Not the Enemy, but Sun Blockers Can Increase Skin Cancer

Medicine is supposed to provide instructions on how to handle dangerous chemicals and procedures safely and to enhance health. Solar radiation is dangerous and will cause skin cancer if used inappropriately, but solar radiation is also needed to produce vitamin D in skin. The public response to the medical mandate to limit solar exposure to reduce radiation-based skin cancer resulted in increased use of solar-blocking lotions. Unfortunately, the result was that some people spent more time in the sun, assuming that avoiding sun burns meant that they were avoiding skin cancer. Unknowingly they had shifted their skin exposure down from doses sufficient to kill cells and cause inflammation, to levels sufficient to just cause solar mutagenesis -- the lower exposures were optimal for skin cancer production.

Spare the Sun and Spoil the Child

Babies and children are the most sensitive to solar radiation induced skin cancer and need protection from over exposure, but the public response to medical advice has been to avoid prudent exposure to the sun. Now kids in the U.S. are showing symptoms of rickets, a vitamin D deficiency disease common during early industrialization, in which air pollution, urban poverty and factory work limited solar exposure. Babies in strollers are completely covered. One frightening consequence of this over-reaction could be a resurgence of poor bone growth that in the 1920’s resulted in the development of the now-trendy Cesarean section procedure to accommodate women with malformed pelvises due to rickets.

Rickets Is Rampant

Ubiquitous vitamin D deficiencies due to inadequate sun exposure is compounded by inadequate sources of dietary vitamin D and inappropriate medical interventions. Most vitamin D deficiencies go unnoticed, because the typical symptoms of deficiency mimic other forms of inflammation. When serum levels of vitamin D are actually measured and found to be inadequate, supplements of 600-1000 iu/day of vitamin D3 are prescribed. Unfortunately, there is seldom followup testing and a recent study indicates that most treatment for vitamin D deficiencies is inadequate -- much higher doses, ca. 2-5000 iu/day are required to reach optimum levels. Most people are and remain vitamin D deficient.

Scourge of Scurvy

Vitamin C deficiencies are also a problem. Most people get enough vitamin C to avoid losing their teeth (vitamin C is needed for collagen production), but subclinical deficiencies still produce chronic inflammation. The major cellular anti-oxidant is glutathione, but vitamin C is another major defense against reactive oxygen species (ROS). An increase in ROS triggers oxygen stress and inflammation. Deficiency of vitamin C indicates that more vitamin C is being used up than is being replenished in the diet. Numerous metabolic disturbances associated with other deficiencies or infections can result in vitamin C depletion and chronic inflammation. Most people are vitamin C deficient.

Vegetable Oils Are the Problem, Not the Cure

Medical advice to avoid saturated fats in meats and shift to omega-6-rich vegetable oils is a major contributor to chronic inflammation and modern degenerative diseases. The original claimed association between saturated fat consumption and cardiovascular disease was tenuous, but produced a glacial shift in diet toward consumption of omega-6 fatty acids, e.g. corn and soy oils. The medical dependence on measurements and treatments of LDL, has outweighed the actual data in the biomedical literature -- LDL levels are not important in cardiovascular disease. Drugs that lower LDL, serum cholesterol, are only effective in reducing heart disease, if they lower LDL by lowering inflammation. The risk factor is the inflammation, not the LDL level. Agricultural practices that use grain over grass further reduce the omega-3 fatty acid content of meat and increase the inflammatory omega-6 fatty acid level.

Statins Are a Problem, Not the Cure

Statins are broad spectrum disrupters of the function of many different enzymes and proteins. They were originally isolated from fungi based on their ability to poison bacteria, i.e. they are antibiotics. They disrupt fat metabolism and thereby lower LDL levels, but they also cause many undesirable and potentially dangerous side-effects. One of these actions is to block inflammation triggered by activation of the inflammation transcription factor, NFkB. By blocking NFkB activation, some statins lower inflammation and thereby decrease cardiovascular disease. This activity is similar to aspirin, which acts on COX-2 as well as directly on NFkB. Both statins and aspirin (NSAIDs) have multiple activities on numerous areas of cellular metabolism. The activities of both include reduction in inflammation, but they also produce other undesirable side effects. Chronic inflammation is better treated by diet, exercise and traditional herbs and spices, rather than more dangerous statins.

Water Is Miraculous, but just Satisfy Your Thirst

If you are thirsty drink tap water. There is no improvement in health by drinking some extra amount of water each day. Drinking water in plastic bottles from magical sources provides no improvement in health. Much of the “spring water” with designer labels is only locally bottled tap water. The plastic bottles are an ecological disaster and the “purified” water in the bottles is contaminated with compounds leaching from the bottles. If you want a constant source of water, bottle your own tap water. If you want to avoid the minor contaminants added to avoid bacterial contamination of municipal water supplies, use a simple point-of-use filter.

Starch Is the Problem

Starch is rapidly converted into blood glucose and that spike in blood sugar causes major problems. The foundation of the old food pyramid, grains, is no different than table sugar in being hyperglycemic, i.e. rapidly raising blood sugar. A large muscle mass and high physical activity can minimize the rise in blood sugar, by using up the sugar for muscle energy as it enters the blood. Unfortunately, most people do not have enough muscle and are not physically active enough to be protected from the starch and sugars in their diets. The result is chronic inflammation in the form of metabolic syndrome and degenerative diseases, e.g. diabetes, allergies, depression, acne, infertility, cardiovascular disease, autoimmune diseases and cancers.

One slice of white bread with a meal may be too much starch for some people. The maximum for most people is: one half of a ripe banana or one half cup of a starchy entree such as pasta, potato, rice, or one of the two buns on a burger. The starch needs to be spread over several meals. Eating too much starch with a meal produces intense hunger, as the blood sugar rapidly rises, triggers insulin release and a subsequent crash in blood sugar. Don’t believe any of the diets that recommend starches to replace fats. Many “lite” diet foods are more unhealthy than the higher fat originals that they replace. Replacing saturated fats with saturated starch is dangerous. The temporary high blood sugar level produces the increased health risks routinely associated with diabetes.

Insufficient Food Is the Problem -- Insufficient Minerals

It takes only 2-3000 Calories per day to energize most people. That means that most people can eat their day’s worth of calories with the sandwich plate at a fast food restaurant. That meal will provide an overdose of starch and sugar, but will be deficient in vitamins and minerals. A major dilemma is that it takes so little food to provide adequate energy for a low activity lifestyle, that the choice must be made between obesity and vitamin/mineral deficiencies. Eating just enough to satisfy energy needs results in deficiencies, but eating more to avoid vitamin/mineral deficiencies, results in obesity. The only solutions are to eat supplements to supply needed vitamins, minerals, antioxidants, etc. or increase physical activity and body muscle mass, so that more can be eaten without producing obesity. For most people the solution is a combination of increased physical activity and supplements. That combination is also found to reduce inflammation and the associated risk of degenerative diseases.

It’s the Stupid Diet

The obsession of medicine with drugs and invasive procedures provides additional health risks for patients. Many researchers complain in the biomedical literature that there is insufficient focus on the cause of disease and too much emphasis on the study of the impact of specific drugs on disease symptoms. The result is that in most cases the symptoms are treated and the disease becomes chronic. Of course this also means that the patient is a permanent consumer of health care.

The foundation of all healthcare should be to improve the lifestyle of the patient. Diseases don’t just happen. The biggest contributions of immediate family to disease of an individual are not defective genes, but rather defective diet and lifestyle habits. Our healthcare system is too no fault. People are sick because there is something wrong with how they live. They eat too much or they eat the wrong foods. They don’t get enough exercise to develop a healthy muscle system to support their joints. Most importantly, bad diet and lifestyle choices produce chronic inflammation. Drugs can reduce chronic inflammation, but will also produce additional side effects that will also require interventions. It makes more sense to attack the original causes of inflammation.

Every treatment program should address the pervasive contribution of chronic inflammation by including a diet and lifestyle inventory and an assessment of the cause of the disease that is being treated. An appropriate anti-inflammatory diet and a path toward a more active lifestyle should be the foundation of every treatment plan.

More Inconvenient Truths

I am writing this shouting summary of bottom lines in response to recent good news and bad news. The good news is that Michael Pollan is speaking in Boise, near my home town. The bad news is the recent press coverage of the JUPITER study on statins.

Michael Pollan is one of my heros. He speaks simply and clearly about the role of national agriculture policy in promotion of hazardous foods that lead to profits in the healthcare industry, but death and disease for the US population. Pollan also provides wise advice to solve our problems.

A new statin, Crestor, was shown in the JUPITER study to significantly reduce the risk of cardiovascular events, e.g. heart attacks, stroke, death, in a study population with normal LDL and elevated C-reactive protein, an indicator of inflammation. The press supported the drug maker’s interpretation that the statin provided benefit by lowering LDL in a population with chronic inflammation. What is missing is the clarification that lowering LDL is unimportant in reducing cardiovascular risk. Lowering inflammation lowers cardiovascular risk and there are more appropriate ways of lowering inflammation than using very expensive drugs. It is much cheaper, healthier and effective to switch to an anti-inflammatory diet and lifestyle!

After reading thousands of articles in the biomedical research literature, here are a few of my obvious bottom lines. Diet affects your health and the most fragile stages of development and most fragile organs, are the most sensitive to abuse. Therefore, damaging diets are most harmful to fetuses, newborns, brains, the cardiovascular system and reproductive systems.

• Formula promotes inflammatory bacteria in newborn guts resulting in lower intelligence, disrupted immunity, infections, allergies, obesity, degenerative diseases and autoimmune diseases. Breastfeeding is the only anti-inflammatory answer for infants.
• The US diet (hyperglycemic starch/sugar, high omega-6 to omega-3 fatty acid ratio, HFCS, low vegetable anti-oxidants, low vitamin D/sun exposure, low vitamin C, grain-fed meat instead of fish) is inflammatory.
• The Mediterranean Diet (small portions of starch, low omega-6 oils, no HFCS, high vegetable anti-oxidants, routine sun exposure, adequate vitamin C, fish and grass-fed meat) is anti-inflammatory.
• Inflammatory diets lead to infertility (female and male), problems during pregnancy (e.g. preeclampsia is an omega-3 fatty acid deficiency) and prematurity/low birth weight.
• Mental illnesses of many different types benefit from anti-inflammatory diet and lifestyle. Diet-based brain inflammation may be a major predisposing factor.
• All of the prevailing drug therapies for cardiovascular disease benefit from anti-inflammatory diet and lifestyle. Most of the drugs that reduce cardiovascular events rely on anti-inflammatory activities. Inflammation is the primary cause of cardiovascular disease, not elevated blood lipids/cholesterol.
• Vegetable oils (corn, soy, cottonseed, safflower) are rich in omega-6 fatty acids and are dangerously inflammatory. These polyunsaturated oils are less healthy than saturated fats. Olive oil is the most healthy.
• Reasonable routine exposure to the sun could eliminate inflammatory vitamin D deficiencies.
• Obesity is inflammatory, but diet-based inflammation may also be a major contributor to obesity.
• Genetic predisposition to specific diseases is triggered by diet-based chronic inflammation.
• Diseases and disabilities associated with aging are symptoms of mismanaged chronic inflammation typically resulting from decreasing muscle mass and increasing fat.
• Sensible diet and lifestyles could dramatically improve quality of life and reduce healthcare expenditures in the US.

Prescription: eliminate vegetable oils, eliminate HFCS, eliminate trans fats, use olive oil, reduce starch, eat vegetables, eat more fish and less meat, get daily sun, use fish oil supplements, get frequent muscle-building exercise, and stay lean.

2009: What I Learned Last Year

This year followers of this blog checked in more than 100,000 times to read my 150 articles on diet, inflammation and disease.  I learned a lot and I hope that my readers gained some insights into anti-inflammatory food choices that are helpful in pursuing enhanced health.  Here is a status report.

What We Eat Contributes More to Disease Risk than Genetics

I started this blog to try to understand how food, exercise, sun exposure, etc., contribute to health and disease, because I was shocked that recent, comprehensive studies demonstrated that genetic defects were only minor contributors.  I am trained as a molecular biologist and I search for explanations of disease in terms of the interactions of the proteins coded by the genes in our cells.  History of defective genes that code for defective proteins in sickle-cell anemia, Huntington’s disease or ALS, suggested that personal genetic defects might explain personal diseases.  Fortunately, it appears that in most cases genetic defects only matter when our actions produce chronic inflammation.  What we eat is far more important than our genetics in determining if we are going to suffer from allergies, autoimmune diseases, degenerative diseases, various forms of mental illness or cancer.  If we eat to avoid inflammation, in most cases it doesn’t matter how genetically defective we are.

Diet-Based Inflammation Is the Major Risk

Modern diets rich in starch/sugar/fructose and polyunsaturated fats (omega-6 oils), and deficient in saturated fats and omega-3 oils produce the chronic inflammation that forms the foundation of most diseases.  Vegetable oils, such as corn, soy or safflower oils are inflammatory and should be eliminated from our kitchens.  We should only use olive oil, butter or lard.  Saturated fats from meat, dairy and eggs are healthier than polyunsaturated vegetable oils.  There was never adequate scientific data to justify the shift from saturated fats to polyunsaturated vegetable oils.  That was a tragic, unscientific medical error that contributed significantly to deteriorating health in the developed/developing world.

Anti-Inflammatory Diet and Lifestyle Is the Cure

It came as a surprise to me that simply eliminating inflammatory foods could prevent most diseases.  After diseases have developed, it is harder to reverse the process and return to health, but even in that case, diet is of paramount importance.

Back to Basics of a Healthy Diet (the Food Pyramid Is Wrong)

•   Starch/sugar/fructose are inflammatory.  Low carbohydrate is the healthiest diet.
•   Grains, even whole grains, and especially cereal are a big part of the problem and should be avoided.
•   Fat and not carbohydrates, should be the major source of dietary calories/energy.
•   Saturated fats are healthier than vegetable oils -- use olive oil and butter.
•   Meats/fish (not fed on grains) are healthy.  A healthy vegetarian diet is difficult.
•   Leafy vegetables are a good source of healthful antioxidants.
•   Fruits and fructose are inflammatory and should be eaten sparingly.
•   Healthy gut bacteria are important.  Eat fermented foods with live bacteria, e.g. yogurt.

Living with Inflammation

Chronic inflammation can lead to many problems that diet and supplements can help to remedy.  For example, vitamin D deficiency is an epidemic in America, because chronic dietary inflammation appears to compromise the ability to make vitamin D in the skin with sunlight.  Most individuals eating a diet high in polyunsaturated fats, starch and high fructose corn syrup, are deficient in vitamin D and would benefit from a vitamin D3 supplement of at least 2,000 IU per day.  Vitamin D deficiency also contributes to inflammation.  Fish oil supplements can also help to reduce dietary inflammation and should always be taken with at least equal amounts of saturated fats in the same meal.

Resolve to Eat Your Way to Health

It is easy to avoid most diseases by avoiding dietary inflammation.  Since chronic dietary inflammation produces depression, lethargy, obesity and a lack of energy, a healthy anti-inflammatory diet will also lead to weight loss, increased energy and reduced symptoms of aging.  Most symptoms of aging and disease are actually poorly managed inflammation that exposes genetic defects.  Most people increase in inflammation with age, but proper diet can avoid this risk to health and prolong youthful activity.    The healthiest resolution for the new year is to stop eating blatantly inflammatory foods (starch and vegetable oils) and start eating more spicy meats, fish and leafy vegetables.

Statins and Atherosclerosis

A recent study (JUPITER) on the statin Crestor was ended prematurely when the drug was shown to dramatically reduce vascular events. The statin was tested on patients with chronic inflammation as judged by elevated C-reactive protein, but with low LDL. These patients would not normally be treated with statins and therefore represent an immense new market for statins.

Statins are supposed to act by interfering with the synthesis of cholesterol and thereby lowering the serum concentration of the lipid carrier LDL. Lowered LDL is supposed to decrease vascular disease that is aggravated by accumulation of cholesterol at sites of inflammation on the surface of blood vessels.

Unfortunately the data linking cholesterol production, LDL levels and vascular disease is weak. Thus, it is possible to lower LDL and have no impact on cardiovacular disease statistics. The recent study on Crestor was interpreted as being support for the link between LDL levels and vascular disease, but I think it shows something very different.

There is increasing evidence that vascular disease is based on diet-based chronic inflammation and that statins have a mild impact on reducing inflammation. It follows then that statins will reduce inflammation enough to have an impact on vascular disease, independent of effects on LDL levels. The Crestor study actually showed that patients with low levels of LDL but chronic inflammation benefited from lowering of inflammation. The LDL levels were unimportant. Reducing inflammation was the point and using statins to reduce inflammation is unnecessarily expensive and ineffective. Adjusting diet makes a lot more sense.

Drug companies are already pushing for increased use of statins on larger segments of the US population to provide prevention from atherosclerosis, stroke and heart disease. This would be immensely expensive with marginal returns. It is also just treating the symptoms without addressing the cause.

The solution to cardiovascular disease is dietary. Omega-6 oils and low availability of omega-3 fish oils is the major cause of the chronic inflammation that is the major risk factor for cardiovascular disease. The major US vegetable oils, corn, soybean, cottonseed, safflower, need to be drastically restricted and olive oil needs to be encouraged. We need to recognize that saturated fats are safer than the omega-6 polyunsaturated fats that have replaced them. Elimination of omega-6 vegetable oils and use of fish oil supplements are cheap and effective ways of lowering chronic inflammation.

Cardiovascular disease is also based on decreasing muscle mass, sarcopenia, which is also the basis for increasing chronic inflammation inappropriately attributed to aging. People get less physical exercise as couch potatoes or with decreasing activity as they age. The result is replacement of muscle by fat, and fat is inflammatory. Obesity is an extreme of this trend that leads to high chronic inflammation identified as metabolic syndrome, the prelude to a suite of nasty degenerative diseases: diabetes, atherosclerosis, allergies, cancer, Alzheimer’s, etc.

The obvious bottom line is to avoid all of these problems with an anti-inflammatory diet and lifestyle.

Inflammatory by Design?

Some modern processed foods seem designed to cause chronic inflammation -- they combine inflammatory food commodities to replace natural foods.

Of the first six major components (more abundant than salt) of a popular processed food dressing, only water and vinegar are absent from the list of major contributors to chronic inflammation.

“Ingredients: water, soybean oil, vinegar, high fructose corn syrup, modified food starch, sugar, salt, enzyme modified egg yolks, mustard flour, artificial color, potassium sorbate as a preservative, paprika, spice, natural flavor, dried garlic, beta carotene (color)”

The soybean oil is primarily an inflammatory omega-6 vegetable oil. HFCS is inflammatory both because it causes a rapid spike in blood glucose and insulin, but because the fructose is a sweet sugar that is even more active than glucose in glycation reactions (adding sugars to amino acids or proteins) that produce the advanced glycation end products that menace diabetics and that cross-link collagen and accelerate the aging of skin and connective tissue. The food starch and sugar both contribute to inflammation through rapid spiking of blood glucose and insulin.

This mayonnaise substitute would be expected to be highly inflammatory and I would recommend that anyone trying to minimize chronic inflammation using fish oil omega-3 supplements should stick to the real thing and pay careful attention to any oils added. Mayonnaise can be whipped up from egg yolks and olive oil. Flax seed oil could also be used -- it isn’t very effective as an anti-inflammatory omega-3 oil, but it is safer than the omega-6 rich vegetable oils. The short, 18C, omega-3 fatty acids can be lengthened to anti-inflammatory 20C (EPA) and 22C (DHA) versions, but the omega-6 fatty acids inhibit that conversion. In this context, I think that saturated fats would be safer than the inflammatory omega-6 soybean oil or its even more incendiary cousin, corn oil .

I am very skeptical of the evidence used to advise the use of unsaturated vegetable oil in place of saturated fats for heart health. Lowering LDL and triglycerides by diet or drugs does not apparently lower heart attack risk. I think that the data all point toward chronic inflammation as the actual culprit. All of the treatments that reduce chronic inflammation (most notably diet and exercise, or COX inhibitors) also decrease the risk of heart disease and death.

Menstrual Pain is Inflammatory

Inflammation is essential to the menstrual cycle. At key points inflammatory prostaglandins are made from omega-6 arachidonic acid to trigger ovulation and menses, the discharge of the blood-engorged lining of the uterus. Chronic diet-based inflammation can result in disrupted ovulation, infertility due to an inability to suppress an inflammatory response to egg implantation, menstrual pain/cramps and premature birth.

Several studies have shown that reducing diet-based inflammation by eating supplements containing long chain omega-3 oils, e.g. fish oil, decreased menstrual pain and cramps. The reduction in chronic inflammation was associated with decreased production of inflammatory prostaglandins that are the cause of the pain and intense uterine contractions. Normally, the diet would provide a balance of omega-3 and -6 fatty acids, which would yield a mixture of anti-inflammatory and inflammatory prostaglandins, and produce an effective discharge through more moderate uterine contractions.

A more recent evaluation of numerous studies on the impact of omega-3 oils on pain associated with menstruation, arthritis, inflammatory bowel disease, etc., showed a uniform decrease in inflammation and pain. The simple summary is that an inflammatory diet rich in omega-6 vegetable oils leads to pain, suffering and premature aging. A more normal diet with a balance of omega-3 and omega-6 fatty acids leads to health and reduced aging.

Typical symptoms of an inflammatory diet are: menstrual cramps, infertility (gestational problems: preeclampsia, prematurity), joint pain, back pain/sciatica, acne, allergies, asthma, autoimmune diseases. There is increasing evidence that obesity not only produces inflammation, but that an inflammatory diet can lead to obesity. An inflammatory diet, especially if augmented with antibiotics, disrupts the normal gut flora and leads to an inflammatory replacement flora that supports chronic inflammation throughout the body.

Chronic inflammation and much of the damage caused by chronic inflammation is reversible by a shift to an anti-inflammatory diet and lifestyle (described elsewhere on this blog.)

references:
Deutch B. 1995. Menstrual pain in Danish women correlated with low n-3 polyunsaturated fatty acid intake. Eur J Clin Nutr. 49(7):508-16.

Goldberg RJ, Katz J. 2007. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain 129(1-2):210-23.

Bell RF. 2007. Food and pain: should we be more interested in what our patients eat? Pain. 129(1-2):5-7.

Anti-inflammatory Diet

Components of an Anti-inflammatory Diet (focus on meats, fish, eggs and leafy vegetables)
Note:  All food is unhealthy without gut bacteria adapted to the food.  See other posts on repair of gut flora.

• Low starch and other simple sugars -- insulin and high blood glucose are inflammatory; so use complex polysaccharides (not starch); starch only in small portions (1/2 banana or one side of a hamburger bun) and preferably in unprocessed, less available forms, e.g. coarse ground or fat coated -- bread with butter; less than 30 gm in any meal, less is healthier, grains are frequently a problem -- gluten intolerance
  
• No high fructose corn syrup -- high free fructose (in contrast to sucrose) is inflammatory and contributes to crosslinking of collagen fibers, which means prematurely aged skin; sucrose is much better than alternative sweeteners
• High ratio of omega-3 to omega-6 fats -- most vegetable oils (olive oil is the exception) are very high in omega-6 fats and are inflammatory and should be avoided; omega-3 fats from fish oil cannot have their full anti-inflammatory impact in the presence of vegetable oils; omega-3 supplements are needed to overcome existing inflammation -- take with saturated fats
  
• No trans fats -- all are inflammatory
• Probiotics and prebiotics -- the bacteria in your gut are vitally important in reducing inflammation; most of the bacteria that initially colonize breastfed babies and are also present in fermented products seem to be helpful; formula quickly converts baby gut bacteria to inflammatory species and should be avoided completely for as long as possible to permit the baby’s immune system to mature (at least 6 months exclusive breastfeeding.)
• Saturated fats are healthy and reduce the peroxidation of omega-3 fatty acids at sites of local  inflammation, e.g. fatty liver.  Saturated fats should be the major source of dietary calories.
• Vegetable antioxidants -- vegetables and fruits, along with coffee and chocolate supply very useful, anti-inflammatory anti-oxidants
• Sensible daily supplements: 1,000 mg vitamin C; 2,000-5,000 i.u vitamin D3 (to produce serum levels of 60ng/ml); 750 mg glucosamine
• Associated anti-inflammatory lifestyle components:

exercise (cardiovascular and muscle building),

minimizing body fat,

dental hygiene
vagal nerve stimulation

Health Diagrams III — Inflammation from Cell to Tissue

---All 200 Posts---

I have explained my perspective in diagrams of the relationship between diet, gut flora and disease:

Health Diagrams I — Gut Flora and Diet

and of the interaction between gut flora, the immune system and autoimmunity:

Health Diagrams II — Curing Autoimmunity and Allergies

Now I am discussing how inflammation, the foundation of most chronic diseases, begins at the cellular level and results in the classic symptoms of tissue inflammation: redness, heat, swelling and pain.

NF-kB is the Transcription Factor that Controls Inflammation Genes

Of the 23,000 human genes, about 1,000 on each of 23 chromosomes, five dozen, e.g. enzymes involved in nitric oxide (vasodilation and erection hormone), synthesis of heparin sulfate and prostaglandin synthesis from omega-6 fatty acids or cytokines (IL-1, IL-6, TNFa), are associated with inflammation.  These inflammatory genes are turned on or expressed in individual cells, when the inflammation transcription factor, NF-kB, is activated by any of numerous external signals, including inflammatory cytokines, bacterial or fungal cell wall materials (LPS or beta-glucan), advanced glycation end products (AGE, e.g. HgA1C, resulting from high blood sugar) or reactive oxygen species (ROS, e.g. super oxide, from insulin resistance).

NF-kB and Inflammation
Superoxid Causes Insulin Resistance

Inflammation is the Foundation of Growth, Birth, Cancer and Pain

We think of inflammation as the sum of physical symptoms, and our purpose in responding to inflammation is typically to limit its impact.  We try to stop swelling by applying cold or hot, and we take aspirin to lower fevers and stop pain.  We fail to realize that inflammation is essential to the growth and development of many different tissues, and that inflammation is a cycle that leads back to normal function.  

Body tissues, such as the lining of the intestines or the uterus, continually produce new cells to replace the old that are sloughed off.  NF-kB must be turned on for these growth and attrition cycles.  Taking aspirin blocks NF-kB in the gut and stops local development of the lining, resulting in weak areas that bleed.  That is why doctors encourage patients to drink a half glass of water before and after swallowing aspirin tablets. 

Another more dramatic example of control of inflammation is conception, gestation and birth.  Conception and gestation require inhibition of inflammation, to permit growth of a foreign organism (a fetus is half sperm genes) in the uterus.  Chronic inflammation limits the ability of the uterus to suppress immune attack and can produce infertility, which is treated by aspirin and heparin, which suppress chronic inflammation.  The return of inflammation at the end of gestation precipitates labor and birth.  Excess Inflammation produces high levels of circulating inflammatory cytokines, which causes postpartum depression.  Depression and chronic inflammation have the same cytokine profiles, i.e. depression is a symptom of chronic inflammation.

Birth and Inflammation

Proliferation, or enhanced cell division, is another aspect of inflammation and is also the foundation for cancer.  That is the reason that some doctors recommend low dose aspirin to reduce colon cancer.  Similarly, since inflammation is the basis for coronary artery disease, doctors sometimes recommend low dose aspirin, although this is controversial.  Doctors also use aspirin as a so called blood thinner, since it blocks inflammatory signaling in platelets and discourages clotting.  Inflammation of nerve cells is experienced by the brain as pain.  

When it is understood that inflammation is an essential feature of many normal, healthy cell and tissue functions, then “inflammation," with its negative connotations, becomes a misnomer.

NSAIDs Inhibit Inflammatory Prostaglandin Production

Aspirin directly inhibits NF-kB activation inside the cell, but it also chemically modifies COX, the enzyme that converts omega-6 polyunsaturated fatty acids (common in polyunsaturated vegetable oils) into inflammatory prostaglandins.  Other NSAIDS (Non-Steroidal Anti-Inflammatory Drugs) just inhibit COX, but Aspirin transfers its acetyl group to make acetyl-COX, which has a new activity that converts omega-6 fatty acids into anti-inflammatory prostaglandins.  The high omega-6 fatty acid content of vegetable/seed oils, such as corn, soy, canola, etc. is why these oils, in contrast to olive oil or butter, are inflammatory.  Omega-3 fish oil is anti-inflammatory, because it is converted to anti-inflammatory prostaglandins.  Plant omega-3 fatty acids are shorter and are not converted to prostaglandins, but inhibit omega-6 conversion.

Aspirin

Nitric Oxide, Vasodilation and Viagra

Swelling is caused by vasodilation, the relaxation of blood vessels, and accumulation of serum in the tissue.  This vasodilation also makes the tissue red and warm from the increased amount of warm blood in the capillaries.  Vasodilation is caused by nitric oxide, NO, that is produced by an enzyme under the control of NF-kB, which takes the nitrogen from arginine (or nitroglycerine).  The NO diffuses easily and binds to receptors that produce an amplified signal, cyclic GMP, that relaxes the muscle cells surrounding blood vessels.  [Viagra is potentially dangerous, because it just exaggerates the amplified signal and obscures the underlying vascular damage, e.g. hypertension, that causes erectile dysfunction by blocking normal vasodilation.]

Nitric Oxide and Erectile Dysfunction

Hot/Cold and Endorphins

The dilemma of whether to use hot or cold therapy to block inflammation is based on a misunderstanding of what the temperature changes are actually doing.  Changing the temperature of the skin alters the structure of sensory proteins in nerves of the skin and triggers signals to the brain that register as hot or cold.  Chemicals, e.g. capsaicin or menthol, can have the same effect without changing skin temperature.  The important response for inflammation control, is return signals from the brain that release neurohormones, e.g. endorphins, from different nerves that reach not only some of the skin that was hot or cold, but also deeper tissue.  The endorphins block inflammation and all of its symptoms.  That is why chemically treated pads are more effective than icing or changing from hot to cold, because "hot" and "cold" signaling chemicals can be applied simultaneously.  None of the treatments is more than skin deep.  Actually chilling or heating tissue below the skin is damaging and causes more inflammation.  Low dose Naltrexone may be effective in some cases of chronic inflammation, by stimulating systemic rebound endorphin production.

Dr. Oz, Pain, Hot/Cold Receptors

Lymphocyte Offloading, Mast Cells, Heparin

Rosacea is a group of diseases that involve inflammation of the face in an exaggerated blush.  Any of the signals that would lead to blushing cause intense vasodilation.  A blush is fleeting, but rosacea is made chronic by another aspect of inflammation, offloading of lymphocytes.  Large numbers of lymphocytes accumulating in response to a local infection would produce pus.  In the case of rosacea, the distributed leucocytes, including neutrophils, respond to the blushing signals by producing inflammatory signals, such as P protein.  The result is cycles of inflammation, autoinflammation.

Mast cells can also be offloaded from blood vessels and provide a link between the immune system and inflammation.  Mast cells display IgE receptors on their surfaces, which bind antigens and trigger release of histamine, heparin and protease.  Histamine is a neurotransmitter that binds to receptors on blood vessels and nerve cells.  In the gut, histamine mediates many digestive processes.  Heparin released along with  histamine, coats the gut and prevents attachment of pathogens by competing for binding to the heparan sulfate proteoglycans (HSPGs) that form the surface of cells that line the gut.  [Heparin is the most common drug used in hospitals and is produced from intestines of cattle and hogs in the meat industry.]  Heparin also binds and inactivates the proteases released from mast cells.  Upon release, the now active proteases attack and activate receptors on nerves and immune cells.

Mast Cells and Heparin

Heparin is Anti-Inflammatory

Heparin is the most negatively charged polysaccharide, mediates most of the receptor/hormone interactions at cell surfaces; facilitates amyloid plaque formation, e.g. in Alzheimer's, atherosclerosis, diabetes, dementia; and controls numerous protease reactions in the complement system and clotting, etc.  There are hundreds of heparin-binding proteins.  Heparin is produced in secretory granules of mast cells by the action of heparanase on heparan sulfate proteoglycans. Heparin is a mixture of small fragments, oligosaccharides of heparan sulfate polysaccharides.  Heparin is anti-inflammatory and is administered to facilitate conception and gestation.  Inflammation also inhibits the genes involved in heparan sulfate proteoglycan production and since HSPGs are a major component of basement membranes of tissues and provide the barrier function of blood vessels in kidneys and brain, inflammation leads to proteinuria and loss of the blood brain barrier.  Since HSPGs have a short half life of six hours and are rapidly recycled, heparin added to the blood is rapidly absorbed by vessels, and heparin taken orally is absorbed by intestinal cells, but does not reach the blood.  HSPGs and heparin are central components of immunity and inflammation.

Heparin and Inflammation

Inflammation Blocks Skin Synthesis of Vitamin D from Cholesterol

Inflammation blocks solar synthesis of vitamin D in the skin and is more important than skin pigmentation, use of sunblock or latitude in producing vitamin D deficiency.  The vitamin D content of food is negligible compared to solar production in the skin.  It is not surprising that rising chronic inflammation is also accompanied by rising vitamin D deficiency.  Vitamin D supplementation is usually ineffective in curing vitamin D deficiency, because the supplements are too low and very high levels of supplemental vitamin D are required to reverse underlying chronic inflammation.  Statins are very effective at blocking cholesterol synthesis and although reducing cholesterol has minimal impact on the target, cardiovascular disease, it dramatically reduces vitamin D causing muscle pain, etc.

Most vitamins are enzyme cofactors synthesized by gut bacteria and used as quorum sensing signals during formation of biofilms.  Vitamin D, in contrast, is a steroid hormone and receptors for vitamin D are inside cells.  The receptor/vitamin D complex is transported into the nucleus where it acts as a transcription factor to control the expression of genes.  Vitamin D controls the expression of defensins in the crypts of the villi of the small intestines.  The antimicrobial activity of defensins is based on the basic amino acids (arginine and lysine) of its heparin binding domains.  Vitamin D also interacts with NF-kB in the nucleus and modulates inflammation.

Inflammation and Vitamin D

Bacteria and LPS

Lipopolysaccharide is a wall component that is indicative of bacteria, just as beta-glucan is indicative of fungi, and both are intense activators of NF-kB and inflammation.  LPS is released from damaged bacteria, e.g. by antibiotic treatment, binds to receptors on the surface of intestines and stimulates inflammation with release of NO, which produces diarrhea.  Food intolerances, which are based on incomplete digestion of food components, because of an incomplete gut flora (immunological responses/food allergies are rare) are probably also the result of LPS release from gut flora and inflammation.

Innate Immunity is also Triggered by LPS

The basic defenses of humans against microorganisms are mediated at the cellular level by triggering molecules common to all microorganisms, e.g. LPS for bacteria.  The responses are equally general: lysozyme to digest bacterial wall peptidylglycan, lactoferrin that binds iron and yields antibacterial peptides.  LPS (and inflammatory cytokines) also stimulates the liver to produce CRP (C Reactive Protein) that binds to choline on bacteria as the first step in phagocytosis and DNAse I that digests NETs (neutrophil extracellular traps) that are the DNA and histones released by triggered neutrophil cells that enmesh bacteria for engulfment by phagocytic cells.  [NETS plug peripheral catheters and can be cleared with probiotics that stimulate DNAse I release from the liver.]  NETs are also present at sites of inflammation and the accompanying nuclear proteins have the basic triplets that stimulate immune presentation and act as autoantigens, i. e. produce anti-nuclear antibodies, in the absence of adequate Tregs.

Diet and Inflammation

The diagram outlines the interactions that produce the tissue symptoms of inflammation.  Many components of modern diet can trigger inflammation:

Sugars and high glycemic starches raise blood sugar and enhance AGE/HgA1C.

Vegetable oils high in omega-6 oils are converted into inflammatory prostaglandins.

Wheat and other grains have high glycemic starch and insoluble fiber that is inflammatory.  Gluten is inflammatory.

Antibiotics damage the gut flora and produce vitamin deficiencies, autoimmunity and allergies.

Food intolerances result from damaged gut flora and produce gut inflammation.

Fish high in omega-3 EPA and DHA are anti-inflammatory.

The Anti-Inflammatory Diet

Health Results from a Balance of:

Diet (meat, fish, eggs, dairy, vegetables), containing macronutrients of protein, starch 30-100 g/d and fat (low omega 6/3 and saturated fat for most calories), and micronutrients

Soluble Fiber, e.g. resistant starch (consult Free the Animal), inulin, pectin, (plant polysaccharides, animal GAGs)

Gut Flora, diverse and adapted to dietary soluble fiber,

Exercise

Resistant Starch, Panacea, but Why?

Mark’s Daily Apple provides an authoritative diet guide (except for the gut flora).

Hazards of Air Travel: DVT

Deep Vein Thrombosis (DVT) -- clots in your veins

Air travel during the holidays means sitting quietly for hours while the blood pools in the major veins of your legs. This is a test. How have you been eating lately? If you stuck to an anti-inflammatory diet and got your exercise, just fidgeting a little and flexing your legs ever once in a while should avoid clots. If you are the typical sedentary American with an inflammatory diet, then worry. One tenth of you will typically have clots in your leg veins after a long flight.

Rolling stones gather no moss, and the same is true for rapidly moving red blood cells (RBCs). Keep them moving and they don’t stick together. Slow down RBCs traveling along sticky vessel walls and you have problems. RBCs have no nuclei and since the intracellular secretory system originates from the outer membrane of the nucleus, red blood cells don’t secrete anything. RBCs just age until they are removed by the spleen. So RBCs just move passively with the rest of the blood.

Another player in clot formation is the platelet. Platelets are cell fragments. They are formed by extrusion and shearing. The process is like bubbles forming as you blow air through a child’s bubble wand. Cells in the bone marrow are squeezed through a grid and the extruded fingers of the cells are blown away in the blood flow as platelets. The electron micrograph shows a platelet between and RBC and a white blood cell. Platelets don’t have any active cell machinery, so they are just little bags containing secretory vesicles that can be released by triggering of receptors on their surface. Platelets are only good for one shot of release.

Platelet release of secretory contents is triggered by norepinephrin, ADP and PGI2, an inflammatory prostaglandin produced from the omega-6 arachidonic acid. Norepinephrin is one of the fight-or-flight hormones that prepares the vascular system for damage control. ADP is released from other activated platelets and insures that isolated platelets are not randomly activated.

One of the proteins released is platelet factor 4. I have illustrated PF4 and the strip of basic amino acids (blue) that girdles the protein are readily apparent. PF4 binds strongly to heparin. Since the clotting process is normally under heparin inhibition, PF4 release from platelets removes the heparin inhibition and promotes clotting. ADP is also released and promotes further activation of other platelets.

Clot formation occurs in response to stress (norepinephrin), damage (vascular inflammation) and a consensus of platelets (ADP). Chronic inflammation can mimic this combination of signals through its impact on heparin metabolism. My research suggests that inflammation lowers heparin synthesis. An example of this effect is kidney damage caused by diabetes. High blood sugar causes inflammation of the kidney blood vessels, this reduces heparin production and since heparin lining the vessels is needed to retain proteins as blood is filtered in the kidney, protein is lost into the urine, i.e. proteinuria. Similarly, chronic inflammation can disrupt the blood brain barrier that is also made up of heparin.

A major source of chronic inflammation is an inflammatory diet. A recent research study indicated that a typical inflammatory American diet leads to elevated risk for deep vein thrombosis. Alternatively, an anti-inflammatory diet rich in B vitamins and omega-3 oils minimized DVT. Saturated fats had no impact, consistent with the lack of evidence supporting the shift from saturated fats to toxic omega-6-rich polyunsaturated vegetable oils.

So, the best thing that you can do to protect yourself from clots when you travel over the holidays, is to eat right and get your exercise, before you travel. Avoid starch (in large amounts) and polyunsaturated vegetable oils (except olive oil.) Corn oil, soy oil, cottonseed oil and safflower oil are particularly inflammatory. Eat plenty of veggies and fruits and enjoy the turkey and cranberries. Make sure that the only sweeteners used are sugar and honey (avoid high fructose corn syrup.) Light corn syrup is the stealth form of HFCS -- it may be lower in calories, since fructose is sweeter than sugar, but it is highly inflammatory! (Research also indicates that fructose causes premature wrinkling and skin aging, by enhancing the crosslinking of collagen. HFCS also causes type II diabetes in lab animals.)