Search the Community
Showing results for tags 'oxalate'.
Found 4 results
Monique Attinger posted an article in Summer 2015 IssueCeliac.com 11/03/2015 - Many people today are dealing with the need to be gluten-free, whether from allergies, intolerance or celiac disease. Being gluten-free can be the difference between being healthy and having chronic, potentially debilitating, symptoms. However, sometimes being gluten-free is not enough. The challenge with a gluten-free diet is that many of the most popular gluten-free flours are actually high in oxalate! Oxalate is a toxin that occurs naturally in most plant foods, but at very different levels, some relatively safe, and some not. Oxalate can even kill at high enough doses. The scientific challenges in the oxalate field, as well as oxalate's potential relationship to celiac sprue, were discussed in the feature article by Susan Costen Owens which appeared in the Spring issue of this journal. In this follow up article, you'll find the practical advice on how you can reduce the level of oxalate in your gluten-free diet. A great example of a popular high oxalate gluten-free flour is almond flour. Almonds are one of the very highest oxalate foods, with about 300 mg of oxalate for one half cup of whole nuts. Given that you will actually have more nuts in a half cup of flour than you will in a half cup of whole nuts, you could have 400 or more milligrams of oxalate in that single half cup of flour. So, your daily morning muffin made with almond flour could be 200-250 mg of oxalate. This means that you may not feel as good on your gluten-free diet as you might expect because your digestive tract can be suffering with ongoing inflammation from a new source – oxalate. Now 250 mg of oxalate might not seem so bad – unless you consider that a low oxalate diet is defined as 40-60 mg of oxalate per day! That makes your morning muffin the equivalent of 4-5 days worth of oxalate, for someone who is eating a typical low-oxalate eating plan. If you've been eating a lot of nut flours, you might be wondering what you can substitute instead? The one nut flour that is low oxalate is coconut flour. This can be a great option, if you like the density of nut flours, and want a flour with higher nutrition. All other nut flours are high; most seed flours are high too. Nuts themselves are some of the highest oxalate foods in nature. Baked products made with nut flours will be particularly high in oxalate – and if you add chocolate, you compound the problem. Unfortunately, this is more bad news for lovers of chocolate baked goods. Chocolate is another extremely high oxalate ingredient: cocoa has more than 35 mg of oxalate per tablespoon and the substitute carob, is no better! Given that many baked goods could easily have 1-2 tablespoons of chocolate or carob per serving, you can see how your oxalate intake could really add up. Of course, this doesn't include the fact that many baked goods – like brownies – will combine both cocoa and nuts, for a double hit of oxalate. The same problem arises with many of our common gluten-free baking flours and spices. They can often add an overload of oxalate to each serving, with the potential for problems later as oxalate accumulates in the body. So, how can you avoid gluten, and not introduce more of a known toxin into your body? The trick is knowing enough about oxalate to avoid it effectively. The first thing to learn is how to get flavor in your food without the oxalate. Oils and extracts are typically much lower in oxalate than the whole herb or spice, and yet retain the flavor for baking and cooking purposes. The process by which oils are pressed and extracts are made appears to leave the oxalate behind. This rule of thumb gives us a way to get the taste we want, and avoid oxalate. For instance, to get a chocolate taste without too much cocoa, you can carefully craft a recipe that balances the use of cocoa with chocolate extract, chocolate flavoring and even a bit of coffee. Using food grade cocoa butter, which has zero oxalate, in place of butter or oil, is another way to boost that chocolate flavor. If you use the lowest oxalate flours as well, you leave some room for a bit more cocoa because you are not adding a lot of oxalate in the flour. By doing this, you can get the flavor you want while avoiding the oxalate. Another example of baking smart is an almond flavored cookie. You can actually make a cookie with almond oil as well as almond extract for extra taste – while almonds themselves are extremely high, both the oil and the extract have almost no oxalate at all! This concept of using oils and extracts is particularly important if you like the sweet taste of cinnamon. Cinnamon is a very high oxalate spice with over 38 mg of oxalate for just one teaspoon! Choose instead cinnamon oil or cinnamon extract. Cinnamon oil is available from various outlets that sell culinary oils. You can get cinnamon extract in the supplement section of your grocery or health food store – generally, it is sold in capsules. When cooking with it, you simply open the capsules and put the powdered extract into your dish. Substitute about the equivalent amount of dry extract for ground cinnamon. The second thing to learn is how to pick low oxalate flours. While many of the gluten-free flours are high in oxalate, the process of picking appropriate flours may not be as hard as it first appears. Oxalate is often present in the "bran" of a grain. As a result, most whole grain flours are actually high in oxalate. This seems strange to us because we are told to get more fiber and eat whole grain. But the truth is that not all whole grains are good for us and we can get our fiber in other ways not so tied to oxalate. Interestingly, most starches are low oxalate (even if they come from high oxalate whole foods), in the same way that oils are low oxalate. This means that starches are our friends when we want to cook! Most starches (including potato, corn, green bean and sweet potato) are low in oxalate, and can be used as part of the flour combination in a baked good to get a lighter, fluffier result. Again, the explanation is similar to the explanation regarding oils and extracts: when we remove the starch from even a high oxalate food, we appear to leave the majority of the oxalate behind. But be careful to get starches and not flours when you are dealing with high oxalate whole foods – items like potato flour or sweet potato flour are extremely high in oxalate, and should be avoided. Only the starches are safe on a low-oxalate eating plan. You can consume some medium oxalate foods, and still remain low oxalate overall. This expands the possible flours that you can use. Good options include white masa (which is a corn flour), green pea, lupin, sorghum, and sweet rice flours. While buckwheat and quinoa are also common in gluten-free foods, these grains are very high in oxalate. You should ideally avoid them. So what do you do if you are used to baking with nut flours? If you want high nutrition flours that are much lower in oxalate than nut flours, look to legume flours. Consider black-eyed pea flour (also called cowpea bean flour), garbanzo bean flour, or yellow pea flour. All of these legume flours are low in oxalate. However, because legume flours can be heavy, combine them with low oxalate starches, like corn, rice, green bean, potato or sweet potato starch to get the right texture in your baked goods. When we combine the lowest oxalate flours with others that are medium (and sometimes small amounts of higher oxalate flours), we can get the right kind of flavor and texture, yet remain low in oxalate per serving. A great example is a flour mix that contains a variety of flours. One easy combination of flours is ½ cup of sweet rice flour (medium oxalate), with ½ cup of coconut flour (medium oxalate), ½ cup of potato starch (low oxalate) and ½ cup of cornstarch (low oxalate). This particular flour combination can be used in crepes, and results in a crepe that has the same kind of stretch that you have with gluten flours, because of the properties of the various flours used in the combination. While some of us will be experimental and will like the idea of playing with flours and starches to develop our own recipes, others will not. If you are looking for a good quality gluten-free flour mix that you can use at home, consider Orgran. Another great option for baking (as well as pancakes) is gluten-free Bisquick. So far we've presumed that you are baking or making your own gluten-free items. But what if you are buying packaged gluten-free foods? When looking at baked goods, look for starches in the first five ingredients. So, you should see low oxalate flours early in the ingredients, because these will be the largest components of your baked good. Avoid items with buckwheat flour, hemp, quinoa, sesame seeds, and teff in general. All of these ingredients are so high in oxalate, that even small amounts would be a problem. While tapioca starch and white rice flour are high in oxalate, in smaller amounts, they should be fine. If you are considering reducing oxalate in your diet, the best way to do that is slowly! When you reduce oxalate too quickly, you can experience stressful symptoms as the oxalate that is stored in your body leaves too quickly. The process of oxalate moving out of your tissues and into your blood, seeking then a site of secretion, is called "dumping" by our project since it is a very common experience. This can be the culprit behind digestive symptoms, fatigue, brain fog, rashes and other symptoms. Ideally, you would slowly phase high oxalate foods out of your diet. So rather than completely abandoning your morning muffin made with almond flour, you would slowly reduce your portion by ¼ of a muffin per week, until you were no longer eating an almond flour muffin after 4 weeks. During those 4 weeks, you slowly introduce your new morning muffin, ¼ at a time, which is now made with coconut flour. You would also want to remove only one food at a time in this way – so that oxalate is very slowly phased out, and you can also use up some of the high oxalate foods that you have in your home. It's not only easier on your body to do this change slowly, but it's also easier on your pocket book! Oxalate is not just an issue with grains and flours – it can also be an issue with other foods. So while this article has focused more on the specific issues with gluten-free baking and cooking, there are other high oxalate foods that you need to be aware of if you want to reduce oxalate in your overall diet. You may have heard or seen information that points at leafy greens as high oxalate foods. While such common staples as spinach, beets and Swiss chard are extremely high in oxalate, you can enjoy other greens in a healthy diet. Consider other leafy greens like arugula, turnip greens, mustard greens or certain varieties of kale, like dino / lacinto or purple, to get leafy veggies in your diet. Most lettuces are low in oxalate and high in nutrition, including romaine and leaf lettuce. Eating low oxalate does not have to mean removing whole food groups from your diet, nor losing all your high nutrition options! Many of the common fruits are lower in oxalate and can be incorporated in your diet – including berries. Many people have mistakenly heard that all berries are high oxalate. Testing done by Dr. Michael Liebman of the University of Wyoming shows this is not true! According to test results from his lab, both blueberries and strawberries are low oxalate, and raspberries are medium oxalate. So while you might want to avoid blackberries (which are very high in oxalate), you can safely eat other healthy berries. However, other fruit can be extremely high in oxalate. Citrus can be tricky because it's important to know not just which fruit you are eating, but which parts. Many citrus juices, like grapefruit, orange, lemon and lime, are low oxalate per serving, so you can still get the taste of these items when cooking with the juice. But don't eat a lot of grapefruit – the whole fruit is high oxalate. Similarly, if you use citrus zest for extra flavor, you'll find that it's a problem: the oxalate levels are too high. Sometimes you need to know the variety of a food, or need to watch your serving size. Pears are a great example. Some varieties of pears have tested low; others have tested high. When choosing pears, go for Bartlett (also called Williams pear). Many exotic and tropical fruits are high, including kiwi, figs, papaya, gauva, and pomegranate. Some are so high that they could be dangerous to consume in a single serving! Star fruit has this dubious distinction: it is so high that people have had seizures and even died from eating star fruit when their kidneys were in trouble. It is important to recognize that many of the foods that we think of as being the healthiest may also contain a lot of oxalate. Vegans can be particularly susceptible to eating a very high oxalate diet, as they may be getting their protein primarily from high oxalate legumes, including soybeans. If you want to include legumes in your diet for the fiber and nutritional benefits, focus on the low and medium oxalate legumes. That list includes red, green, brown and yellow lentils, green peas, red kidney beans, tofu, garbanzo beans, yellow and green split peas, lima beans and black-eyed peas. Note that tofu is okay – but whole soybeans are not. This is one of the most challenging aspects of the diet. Some foods are okay in the right form, or with the proper processing. So much as extracts, oils and starches are lower in oxalate than the whole foods they come from, some processed forms of foods are lower than the whole, unprocessed food. So you can eat tofu – but don't eat edamame. A last point that can help you to reduce oxalate in your diet is to consider how a food is cooked. When a food is boiled, you may actually reduce the amount of oxalate in the food. Oxalate can be soluble, and so it will leach into the cooking water, and can then be thrown away. There is no other cooking method that can reliably reduce oxalate, other than cooking or soaking in water. However, this flies in the face of current nutritional advice, which focuses on eating as many foods as possible raw. While you don't have to boil everything you eat – there are a number of very low oxalate veggies and fruits that can be eaten and enjoyed raw – boiling can be a valuable strategy to reduce this known toxin, and leave you with a more nutritious end result. If you have more questions about oxalate and your diet, please see the website www.lowoxalate.info. There is also an associated support group, which is currently at Yahoo, called Trying_Low_Oxalates. In addition, we have a Facebook group with the same name. On Facebook, we also have two additional recipe groups, one of which is focused specifically on vegan eating. These support groups can help you to make lower oxalate choices part of your diet and can also help you gain a perspective on how oxalate may have been affecting other issues in your health. Lower Oxalate Flours, Starches and Products Potato starch Cornstarch Green Bean starch Sweet Potato starch Flax meal / seed White masa corn flour Green pea flour Lupin flour White rice flour Sweet rice flour Coconut flour Black-eyed pea (cowpea) flour Garbanzo bean (chickpea) flour Water chestnut flour Yellow pea flour Low Oxalate per serving General Mills Corn Chex (1/2 cup) General Mills Rice Chex (1/2 cup) Arrowhead Mills gluten-free Popcorn (1 cup) Eden Kuzu Pasta (1/2 cup) Thai Kitchen Rice Noodles (1/2 cup) Annie's Homegrown Macaroni and Cheese, gluten-free (1/2 cup) Tinkyada White Rice Spaghetti (1/2 cup) Lotus Foods Bhutan Red Rice (1/2 cup cooked) Higher Oxalate Gluten-free Products Medium oxalate per serving Udi's White Sandwich Bread (1 slice) Nabisco Cream of Rice (1/4 cup dry) Envirokids Gorilla Munch (1 cup) Orville Redenbacher's Popcorn (1 cup) Mission Yellow Corn Tortillas (1) Tinkyada Brown Rice Spaghetti (1/2 cup cooked) Tolerant Foods Red Lentil Rotini (1/2 cup cooked) Lundberg Brown Jasmine Rice, boiled (1/2 cup) Extremely High Oxalate foods Beans (Anasazi, Black/Turtle, Cannellini, Great Northern, Navy, Pink, Pinto, Red, Soy, White) Cactus/Nopal Carob Cocoa Powder/dark and milk chocolate Fruits (Apricot, Blackberries, Figs, Guava, Kiwi, Pomegranate, Rhubarb, Star Fruit/Carambola) Grains (Amaranth, Buckwheat, Quinoa, Teff) Nuts (Almonds, Cashew, Brazil, Hazelnut/filberts, Macadamia, Peanuts/Spanish Peanuts, Pine) Seeds (Caraway, Chia, Hemp, Poppy, Sesame) Herbs/Spices (Allspice, Cinnamon, Clove, Cumin, Curry Powder, Ginger, Onion Powder, Turmeric) Potatoes (Russet, Burbank, Idaho, Fingerling) Vegetables (Artichoke, Beets, Eggplant, Hearts of Palm, Jerusalem Artichokes, Okra, Plantain, Swiss chard, Spinach, Sweet Potato/Yam) Guide to Lower Oxalate Substitutions (chart on substitutions is used by permission from: https://www.facebook.com/pages/Low-Ox-Coach/551330634959001/) High Oxalate Ingredient(s) What it's used for Lower Oxalate Substitution Spinach Greens in a stir fry Cooks down for sauces / dips ARUGULA. Similar flavour and consistency. Substitute one for one. Beets Greens in a stir fry Sweet root veggie Used for detox For stir-fries, try other greens, like turnip or kohl rabi. You can also use red cabbage for a red veggie (if you need something red). Try boiled carrots or parsnip for dishes that need a root veggie. If you want a gentle detox, try lemon juice in water to start your day. Swiss Chard Greens in a stir fry Steamed Boiled Dino / Lacinto Kale. Lowest ox when boiled. Can also try mustard greens or dandelion greens. Almonds Snack Baking Gluten free crusts For snacks, try pumpkin seeds. For baking, either go to coconut flour (rather than almond flour) or use a lower ox nut and smaller quantities. For bread, try pumpkin seed butter or sunflower seed butter. Pecans or walnuts are the lowest ox nuts. Almond or peanut butter Spread for bread Sunflower seed butter, macadamia nut butter, pumpkin seed butter, golden pea butter (golden pea is the lowest oxalate) Sesame seeds Used for both flavour and as the whole seed While sesame seeds are high, the oil is zero oxalate! So, try using either plain or toasted sesame seed oil to flavour dishes. Most dried beans, including red beans, adzuki beans, black beans, etc Chili Savory dishes Dips Try subbing lower ox legumes like black-eyes peas, red lentils, green and yellow split peas, garbanzo beans and lima beans. Brown rice Side dish Casseroles Stir-fries Sub with either brown rice that is soaked, drained and cooked like pasta (in lots of water), or use white rice. Uncle Ben's is one of the lowest rices. Chocolate / Cocoa Desserts of all kinds! Try lesser amounts of chocolate, or a combination of cocoa and chocolate flavoured stevia. Also, can sub white chocolate in many applications, like white chocolate chips for cookies. In a recipe, sub food grade cocoa butter in place of other specified oils / butter. Tomato sauce Sauces Casseroles Pastas Instead of 100% tomato sauce, sub with 1-2 tablespoons of tomato paste, ½ cup pumpkin or butternut squash puree and water to thin as required. Add appropriate spices for the dish. Black tea Beverages Decaf green tea, many herbal teas or coffee Nutmeg Spice Mace Black pepper Spice White pepper Sweet potatoes Dishes of all kinds Butternut squash or other suitable squash with the right texture and flavour. Onion, carrot and celery to use to start soup One of the most common combinations to start soup or stir fry Garlic, shallot and red pepper is a favourite. You can also use garlic, shallot and green cabbage. Lemon or orange rind Dishes of all kinds Lemon or orange juice, with a thickener. In some cases, lemon or orange extract. Cinnamon Dishes of all kinds Cinnamon extract (purchased in a dry capsule supplement at the health food store. Break open capsules and put contents in your dish). Regular potatoes Boiled, or used in dishes Baked You can boil new, red-skinned, white-fleshed potatoes and then add to dishes. You can also sub cauliflower or radishes, 1 to 1. (Radishes are great cooked!) To sub for a baked potato or for a dish that uses potato raw, try rutabaga or turnip (which can be scalloped or turned into a baked fry.) Regular pasta Usually for main dishes or side dishes Zucchini "noodles", or cornstarch noodles, or other tested and low ox pasta like Shiritaki noodles (which are also low carb and zero calories). You can get cornstarch "angel hair" pasta or Shiritaki noodles at Asian food markets. Oatmeal Breakfast Baking Sub with ½ oatmeal and ½ flax meal for cooked cereal with the same texture but lower oxalate. Turmeric Baking Flavor Sub with curcumin extract. This can be purchased as a health supplement in capsules. Capsules can be opened and the contents added to food and beverages. Ground ginger Baking Flavor Sub with fresh ginger or ginger root extract. From the author: If you have ever been diagnosed with an autoimmune disease and have been trying to lower oxalate, will you participate in the development of this science by filling out a survey? We would also like to find out whether reducing oxalate has affected your autoimmune condition. The link to our survey is here: https://www.surveymonkey.com/r/CMN5KK7
Susan Costen Owens posted an article in Spring 2015 IssueCeliac.com 07/17/2015 - This article originally appeared in the Spring 2015 edition of Journal of Gluten Sensitivity. Why is a researcher whose field for twenty years has been autism now writing an article about celiac disease and its possible relationship to oxalate? This takes a little explaining. My training in graduate school was all about looking into old literature to find pieces of research that had been lost, or were never incorporated into current models. I learned that new science could provide a different context for old findings. The importance of this process came home when more than a decade ago I was sitting at an enormous oval table at the National Institutes of Health where an important meeting was addressing how the heads of various National Institutes of Health and the CDC would handle a theory about a possible environmental trigger related to autism. One scientist rose to the floor, and began to explain his reason for discounting the new theory's importance. He proposed that this theory did not fit into previous models of autism, and began to say that the scientific process worked like the construction of a brick wall. Everything added to that wall should fit into the foundation and bricks that had already been laid. How often does this view of science as being a construction of human beings, rather than a discovery of nature, keep us from accepting new lines of research? Has scientific consensus ever ended up wrong after the appearance of new findings? Yes, many times. In this meeting at the NIH, at that moment, a senior scientist, Dr, Bernard Rimland, rose to the floor. Those who knew this man realized he had singularly changed the view about the science of autism twice, accomplishing these major shifts of thinking during different decades. I don't have a transcript from that meeting, but Dr. Rimland rose to say something like this: "My experience is very different. I find that science is more like a crossword puzzle, in that you may have been working at the puzzle from one end and filled in places that looked correct until you began working from another side and discovered that something you filled in before must have been wrong. That's when you erase the part that you thought had been right, and you find another answer that will make the parts fit from both directions." That speech has been a guiding light to my own research since then, helping me have the motivation to recover all the pieces that were lost or misunderstood or left out from the past whose absence left a model that only approximately provided a place for all the known pieces, but left many other pieces "loose" and unable find a proper fit. In 2005 after spending ten years studying the biological roles of sulfate in the body, I began to investigate another negatively charged ion that travels on the same transporters. I reviewed the published literature on oxalate in any condition, looking at basic science and clinical research over the last two centuries. I was looking for gaps and opportunities for improving the identification of oxalate-related diseases outside the kidney. My work for twenty years had focused most intensely on autism, and I had found that oxalate was high in autism, but this finding needed to be put in context and studied formally. It was mystifying to me why work from basic science about oxalate was only being applied to patients with kidney disease. How could we identify others with oxalate-related disorders? In the fall of 2005, along with several associates, we started our Oxalate Project. Using the same methodologies I had developed in the previous decade using the internet to interact with a broad range of patients, we began seeking those with any condition that was already related to oxalate in the literature, and patients with other conditions where the science took us. Included in this effort was setting up a project at the Autism Research Institute that we named the Autism Oxalate Project. In October of 2006, I attended the International Celiac Disease Symposium in New York City. I was hoping that the findings in oxalate research on malabsorption and intestinal disease, and specific findings on oxalate in celiac disease published since the 1970's were being discussed at this conference. I heard not a word about oxalate there. These scientists probably did not realize that when oxalate levels in the blood become high, it can get stored all over the body where it can produce effects in any potential organ…not just the kidney. I had learned that systemic effects from oxalate could change the course of a condition in patients over years of time. For patients with celiac disease, this storage might have occurred primarily during the years before diagnosis when problems with fat digestion would have increased the percent of oxalate absorption from the diet. In autism, I had learned that, as in celiac disease, some investigators had noticed oxalate's elevation in urine in isolated individuals, but they had been taught by articles in peer-reviewed literature to dismiss this finding as irrelevant when those individuals didn't have kidney stones. Basically, the literature kept saying that kidney stones would always be the first presentation of an oxalate problem—but was that true? Why would that be true? As I began to attend numerous world conferences on oxalate, I was very surprised to find that the only people there besides botanists, were those involved in kidney research. My previous studies in the literature had identified many articles describing oxalate producing effects all over the body and in multiple systems. New work on oxalate transport was finding regulation of oxalate's movement all over the body. Why wasn't this research being applied to patient care outside the kidney and why were certain laboratories insisting on a kidney diagnosis before they would even measure oxalate? Since my own work at that point included running a support group for people reducing oxalate and our doors were open for people with any condition, we had seen patients with more than twenty different conditions report an easing of their symptoms or even complete cures when they brought their oxalate levels down. Would the scientists be able to catch up with this wealth of experience that today has involved more than 17,000 families? Here is an example: I worked with a team of oxalate and autism researchers in Poland to establish the prevalence of oxalate's elevation in autism. The study that this work produced became available online in 2011, but officially went to print in September of 2012 in the European Journal of Paediatric Neurology. It was the first study to examine whether the levels of oxalate in blood plasma would correlate to the levels in 24 hour collections of urine in those who were not in kidney failure. We discovered that the levels in these two compartments did not correlate at all, especially in the controls. This meant that the oxalate field's dependence on urine tests as sufficient to identify those with oxalate problems was probably misplaced. It made sense that the two compartments would not "agree" because oxalate's movement between tissues, we now know, is regulated and its regulation would be different in different organ systems. How many other conditions were experiencing effects from elevated oxalate in blood that were not accurately reflected by only using urine tests? What did we know about variability from day to day, or even rhythms within the day, for oxalate secretion in other conditions? What did we know about how any variability should affect the interpretation of lab results, or our interpretation about the timing and presentation of symptoms in other conditions? A striking finding in our paper seemed to have been also referenced in a paper from Mayo Clinic, showing that urine oxalate in normal controls seemed to stay below the reference level of 0.46 mmol/1.73 m2 (24 hr.) Perhaps the point of the kidneys regulating that level so tightly was to protect the kidneys from risks of kidney stones or nephrocalcinosis, but that particular control of urinary secretion seemed lacking in autism. Scientists were beginning to discover secretion to other compartments, such as the intestines, the lungs, and the skin for example. Why would someone doing research even think to measure oxalate secretion and regulation in these other sites in clinical settings? In the past, everyone had assumed that measuring urine was sufficient. The graph of plasma versus urine looked completely different in those with autism compared to controls. What would a similar graph look like in celiac disease? Would the graph show different patterns at different ages, or before and after treatment with a gluten-free diet? Data from a study from Saccomani et al. may suggest that a limit to urinary secretion may be preserved in children with celiac disease, but would limiting secretion in the kidney sometimes lead to a greater accumulation of oxalate in tissues? Our autism study revealed that there are problems with assuming that a single urine test could be used to screen patients when oxalate could be elevated in blood and causing problems in the rest of the body. More than fifteen years ago (not published but presented at a think tank) I noticed problems in lab tests in autism with what looked like it could be caused by a variability in creatinine secretion. This would create a problem in interpretation for any urine test ratioed to creatinine, but the reason we would see this variability in autism made sense when a rat study recently found that oxalate in the kidney changes the movement of creatinine out of blood and into urine when oxalate was made to be high experimentally. This type of study urgently needs to be replicated in humans before anyone can have confidence that this affect on creatinine isn't compromising our data from spot urine tests. Suddenly it seems very sensible that in the oxalate field, it has become common practice to use 24 hour tests. Readers need to realize that this issue would affect anything measured in urine and ratioed to creatinine, not just oxalate! From data I've reviewed and analyzed statistically from more than a thousand organic acid tests, and from other literature, I also doubt that this single mechanism is solitary in contributing to problems in interpreting urine tests that use this ratio. Can we still legitimately think that physicians should not worry about oxalate levels unless their patients have developed kidney stones? Celiac disease is one of many conditions where high oxalate levels have frequently been found in patients. Some of the other conditions include bariatric surgery, cystic fibrosis, inflammatory bowel disease, short bowel syndrome, autism and more. Are doctors and nutritionists understanding that patients with these disorders will experience risks from oxalate to the rest of their body? Are they noticing when these patients develop issues outside the kidney that their symptoms might be related to oxalate? I've learned that the answers to these questions is most often, no. In our project's work with such patients we have reduced body oxalate levels through strategies of dietary modification, and by the use of specific vitamins, minerals and probiotics that have been shown to reduce oxalate. We've seen these changes alter the expression of their presenting disease in unforeseen but positive ways. It will take decades before all our findings from ten years of work in dozens of conditions can be confirmed by scientific studies. That does not mean these patients have to wait for academic studies to be published to see for themselves if reducing their exposure to this clearly recognized toxin will help improve their own health. Do physicians know that research on kidney stone patients have identified issues in their kidneys that lead to their increased risks of forming kidney stones from oxalate levels that would not produce stones in others? Could oxalate that was elevated in blood and tissues (and currently not being secreted at high levels in urine) cause problems to other parts of the body, contributing in unknown ways to comorbidities like those found in celiac disease? At the celiac symposium I attended, there were so many issues that were being discussed as being unresolved by the use of a gluten-free diet. That surprised me. Could those issues have been triggered by oxalate that was absorbed into the body before a gluten-free diet had resolved steatorrhea? Steatorrhea is the condition where excess fat stays in the feces, possibly causing the stool to float or have an oily appearance. Studies had shown that untreated celiac disease often was associated with steatorrhea. This condition elevates fat in the gut and that fat travels undigested all the way to the colon. Oxalate scientists had found that the fat left in the intestines during the journey to the colon would tie up calcium that ordinarily binds oxalate from the diet. About 80% of the calcium that travels through the gut stays in the gut. The purpose may involve the formation of a calcium oxalate salt in the feces that limits oxalate's absorption in the colon. Otherwise that oxalate could be transferred to blood if it is not first metabolized by the microbes in the gut. This is a bigger problem than the higher amount of oxalate in the diet. This might become a more serious problem when people with celiac disease use new grains that are gluten-free but which we know now are extremely high in oxalate. During the mid-nineteen thirties, prominent groups began recommending adding vitamin D to milk to prevent rickets, knowing that vitamin D enhances the absorption of calcium from the gut. Back then, oxalate research had not yet found a protective role for most of the calcium to remain in the gut to protect us from oxalate. Physicians had advised kidney stone patients to avoid calcium, but later determined that calcium in the diet was protecting patients from absorbing oxalate. Later studies showed that oxalate that remains in the intestines as a free anion (unbound to calcium) can and will be absorbed into the body once it reaches the colon. When this unbound oxalate is taken into the blood, there it was found to be able now to tie up free calcium that was needed to protect our bones and work in our metabolism. Free oxalate could a lso be taken into cells via oxalate transporters where it could disrupt calcium signaling inside cells and wreak havoc in the mitochondria and endoplasmic reticulum. Free oxalate can disrupt activity also in the nucleus where nature has supplied a specific oxalate binding protein. Is this protein sometimes overwhelmed when oxalate gets too high? Before I attended this celiac symposium, I had not heard that some of the autoimmune and cancer risks associated with celiac disease may still be there even with a gluten-free diet. Who was asking what else besides gluten could be contributing to these risks and were they being studied? Was oxalate one of those risks? People on our listserves that help people reduce dietary oxalate were telling us they experienced improvements in autoimmune conditions on a low oxalate diet. No one has had time to examine these reported changes formally yet, but could oxalate have a potential connection to the risks of autoimmunity or even transformed cells in celiac disease patients? I learned to ask these types of questions in graduate school and in the years that followed as I continued to find science that had been learned "out of order", and rejected as an important piece of the science because at the time there were missing pieces that were only discovered later. My intense study of medical literature's missing links brought to my attention so many valuable scientific discoveries that at the time they were published had been cast off as irrelevant. As I started to look intensively for more and more of these lost pieces, I made another astonishing discovery. I learned that we do not fund researchers to go digging through past scientific work to find links that may never be rediscovered after scientists with other priorities and agendas direct research efforts into other directions. Does science proceed linearly? Why should it? Are you personally one of the types of people that when doing a jigsaw puzzle, you first find all the outside pieces, and then start grouping colors and actually have a plan for which piece you will try to find next? My plan is to keep looking for pieces that didn't fit into models in the past to see if today's new findings will finally reveal how they now fit in well with today's insights. I don't think laboratory scientists or clinicians are the best equipped to do this sort of work, but organizations funding science expect that to be where this sort of integrative work will originate. I have found instead that most investigators who are up to their ears in current scientific projects or who are developing protocols for others to follow will not take very much time to dig deeply for lost pieces. There are rare exceptions to this observation. I have actually met a lot of this special breed of scientist, who loves to think outside the box and has respect for what might have been lost and loves to dig through old findings. Nevertheless, sociologists who study such things tell us that most scientific studies are never read outside of a small group of narrow interest and will only have influence for a few years. With this being the general expectations, who is left to do the work of recovering lost work from the past? Who also brings in work from other disciplines previously thought unrelated to a condition? In the oxalate field, molecular biologists have now discovered that oxalate shares transport with sulfate and bicarbonate, which means oxalate also gets into the regulation of pH. While these transporters regulate these ions, they also move a lot of water across cell membranes. In some places, oxalate shares transport with iodine, and of course, that makes us think of things related to the thyroid and all the histories of later onset thyroid disorders and autoimmune conditions. Pathologists found that the older you are, the more your thyroid gland will fill with oxalate, and this can be associated with a loss of thyroid activity. That makes sense now that we understand that these substrates are linked in the way the body handles them. But what about anemia that can develop in celiac disease? Scientists found that transferrin's carbonate ion can be replaced by oxalate if oxalate can gain access to this site at sufficient concentrations. When that happens, unlike the carbonate ion, the oxalate anion won't let go of the iron, so it sequesters iron irreversibly. This mechanism has never been thought to be related to the anemia in celiac disease. What about the tendency towards osteoporosis or osteopenia in celiac disease? Some remarkable studies conducted in the late 1930's (actually after Popeye made his appearance) fed groups of rats a basal diet deficient in a good calcium source, but they made up the rat "RDA" for calcium by using either turnip greens or spinach. Turnip greens are high medium in oxalate content, but spinach is extremely high. The rats fed the spinach, during their lifetime (and many died prematurely), had impaired growth (also seen with celiac disease). They had bones and teeth that wouldn't mineralize. The rats on spinach were unable to reproduce except for one litter of two pups that were quickly devoured by their mother at birth. In contrast, the rats fed turnip greens, which are roughly otherwise equivalently nutritious, completed the study in great health with shiny coats and all the perks of being a healthy rat. Did Popeye deceive us about the benefits of what has become a much more popular food, often called "the healthiest food there is?" By the way, one of these studies was conducted by Campbell Soup Company! Our oxalate project, which makes its home at www.lowoxalate.info with its associated support groups on Yahoo and Facebook, has now served more than 17,000 families in helping them discover for themselves how oxalate has been contributing to health issues…with problems that resolved as they brought down their body burden of oxalate. We've seen this one change fundamentally alter the course of more than twenty disorders, and these disorders are not very much alike. Some are genetic and some are probably not genetic, but are you wondering why they aren't alike if they are all associated somehow with oxalate? With new genetic tools and new basic science to help us, it is now a lot easier to figure that out. Members of the SLC26 family of oxalate transporters that move a special set of nutrients across cell membranes are expressed at different levels and in different combinations in different organs and cell types. Scientists are just now starting to ask the questions about how they may be regulated, or "turned on" or "turned off". When is the immune system involved in this regulation? When may we find genetic differences in the use or expression of these transporters? We already know a few observations related to their expression in the lungs and in the inner ear and in the mucosa, but at this stage in the game, there is much more science about their regulation that we don't know compared to what we already have discovered. We do know now that it was a mistake to think oxalate was only secreted in urine. How many studies in the past based their conclusions on urine being the only place to look? Oxalate is now known to be secreted in the lungs where scientists in Russia have been making much progress in understanding its roles in asthma and COPD, but I would just about guarantee that your immunologist or your pulmonologist doesn't know about that research yet, but it has been going on for years and years. Oxalate is also secreted to the skin and can cause terrible rashes. Is it related to dermatitis herpetiformis? Who has measured for oxalate in those lesions associated with gluten sensitivity? In primary hyperoxaluria, secretion of oxalate to the skin has led to serious lesions that can even turn into gangrene. People on our listserves have reported the swelling of blood vessels in the skin termed livedo reticularis, and others have described and pictured all sorts of skin lesions, including an odd appearance of glitter in the skin that appears imbedded, but glistens beautifully in the sun. No, these people were not vampires! Our bodies not only get oxalate from dietary sources. The body is also producing oxalate internally as a by-product of certain metabolic processes that normally keep oxalate levels low. In the genetic condition, Primary Hyperoxaluria Type I, still believed to be found in only one in a million individuals, these individuals lack a B6-dependent enzyme that ordinarily converts a normal byproduct of metabolism to a very safe amino acid. When this enzyme activity is lacking from this genetic defect or from B6 problems, oxalate builds up inside the cells where it is made and where it might produce local damage. The amount of oxalate produced with the genetic defect is so high that it spills out into the body, primarily from the liver, and produces a condition called oxalosis where oxalate damages tissues all over the body, and in the bones, and the heart, and often leads to death by kidney failure. Through the work of Marguerite Hatch and other scientists, we have learned that signals now being studied will instruct intestinal cells to take oxalate out of blood and secrete it into the stool. Even though a vast literature has associated inflammatory bowel diseases with producing an increased absorption of dietary oxalate through a leaky gut, that is apparently not the whole story. The body has mechanisms to rid itself of normal levels of excess oxalate, but in primary hyperoxaluria Type I, these efforts seem never enough to protect the body. In Mayo's database it was reported that 59% of those with this genetic disease experience abdominal pain. Oxalate is a known inflammatory molecule. Does oxalate secretion to the gut produce inflammation and pain? This certainly needs to be studied by gastroenterologists but does that discipline even know about this oxalate research? Who is showing them this science? Have you ever wondered if there is anyone who ensures that discoveries from basic science are applied by the physician to patient care when the finding isn't related to drug development? We humans do not have genes to degrade oxalate. That is why oxalate, once absorbed into blood can collect in our tissues and cause damage. Nature has provided a way for increased oxalate in our blood to join the contents of our intestines so that it can find and bind calcium in the gut and then can leave in the feces. That is not the only reason oxalate from blood is sent there. The gut is home to microbes that are capable of degrading oxalate. This purposeful removal of a substance toxic to humans happens only if the oxalate-loving microbes are there and healthy enough to perform this service for us. This wonderful system fails, however, in conditions like cystic fibrosis, where continuous use of antibiotics may have killed the microbes that perform this service for us. Unfortunately, even in those without cystic fibrosis, many commonly used antibiotics, like the Z-Pack, can kill our oxalate degrading microbial friends. Another problem is that widely used antibiotics can also kill back the biotin producing microbes in the gut. Why is that relevant to oxalate? An important class of enzymes called biotin-dependent carboxylases, were found to be invaded by oxalate when higher levels of oxalate travel to where these enzymes function. Since these enzymes function in critical roles in the mitochondrion (with only one enzyme of this type serving us in the cytosol) scientists learned that oxalate may seriously impair their enzyme activity, putting our mitochondria in great distress. Scientists also found this interference is fairly easily addressed by high doses of biotin. Many years ago, I realized that doses of biotin being recommended by physicians and others were in all likelihood too low to provide effective restoration of the function of biotin-dependent carboxylases whenever oxalate had become elevated in mitochondria . I read about doctors treating dystonia caused by a thiamine transport defect with high dose biotin at 5-10 mgs/kg/day. Children with this thiamine transport disorder were kept on this dose of biotin for years with no problems, but when the dose was lowered, the dystonia came back. Why are some physicians worrying about giving 5 to 20 mgs a day to grown adults? I can only guess that they were unaware of the literature on biotin's safety and were never able to witness how their patient's lives might change on higher doses. Competition at enzyme active sites will matter much more than blood or urine levels. Unfortunately, we have no way of measuring tissue or organelle levels of oxalate in routine patient care. Clearly, more work needs to be done in this area to see where and when higher doses are needed. Unfortunately, many doctors are in unfamiliar territory with higher doses of biotin, and may be unaware of biotin's track record of great safety even at very high doses. We must ask, if someone is dangerously high in oxalate, which choice will cause more harm to them, taking high dose biotin, or failing to take higher doses of biotin when that could lead to a loss of function of those important enzymes? Do scientists and doctors realize that anything which damages mitochondrial function might also lead to villous atrophy? Did elevations of oxalate happen before the changes that lead to a diagnosis of celiac disease? There are actually many other mitochondrial enzymes known to be inhibited by oxalate. If oxalate seriously affects mitochondrial function, what might that have to do with what else we know about celiac disease? Right now, the first two articles that come up in pubmed when searching on celiac disease and oxalate are articles that should get us thinking. The first is an article entitled, "Subclinical celiac disease and crystal induced kidney disease following kidney transplant". Its abstract says, "Subclinical celiac disease is commonly overlooked and hyperoxaluria is not usually investigated in kidney patients." This article described a patient with hyperoxaluria, but this patient was lacking overt diarrhea, fat malabsorption, or nephrocalcinosis. The article that comes up next on this search speaks of measuring children with celiac disease, and concludes, "In contrast to adults, increased urinary excretion of oxalate was not detectable in children with celiac disease." Was that happening because oxalate that was getting into the blood was being secreted at this age more appropriately to the gut, or the lungs, or the skin, instead? Or had their oxalate been collecting in tissues like the gut, where it might be starting to impair mitochondrial function, possibly leading in time to villous atrophy? It would be hard not to notice that currently in the US, it is becoming popular to try gluten-free eating even if someone does not have celiac disease. That situation also describes several members of my own family who do not have celiac disease, but found out about twenty years ago that being gluten-free turned around our health so significantly that we never were tempted to go back to eating gluten. I had actually gotten the idea to try life without gluten from autism research which had been looking at a different reason to be sensitive to gluten, termed "the opiate excess theory". When I was at the medical library doing research when I was in graduate school, I found this theory discussed in a decades old book talking about schizophrenia. Soon I was privileged to know two of the major scientists working in this area, Paul Shattock and Kalle Reichelt. They found a protein in wheat (gliadin) and in milk (casein) that as they were digested formed peptides that had opioid activity. These peptides were capable of producing signals at opiate receptors meaning they might produce reactions or side effects seen when taking opiate medications. Later work also discovered opioid peptides in soy. The reason that this research might be important to celiac disease is that part of the benefit seen by removing gluten may come from eliminating these opioid signals, but these signals may continue to be a problem if you are still consuming large amounts of milk or soy. Recently, some further implications have appeared in this research area. Another of my autism colleagues, Richard Deth, found at his laboratory that the peptides that form opiates also block the absorption of cysteine across cell membranes. This unexpected finding probably has its biggest implications in the gut (preventing sulfur absorption) and in the brain, where sulfur is regulated a little differently. I recommend his recent paper to tell you more details, but it simply means that some of the benefits people with celiac enjoyed on a gluten-free diet may have been related to this other characteristic of opioid peptides. These same individuals may find that their health will improve even more if they controlled milk and soy. In the second year of our project on oxalate, I spoke at a conference in Germany and was invited for lunch in the home of a family with a child with autism on a gluten-free diet, but I noticed that this child and the children with autism I met in Germany were not doing as well as I was used to seeing in the USA. As I sat at their table, I found out that most of their gluten-free bread was made with buckwheat as a major ingredient. Buckwheat is, a very high oxalate grain. Was this keeping their son from getting better? Because I knew so many children with autism who had done much better than before after they eliminated gluten and casein, this to me seemed a sufficient reason not to reintroduce these foods to children already off these foods as we looked into the role of oxalate in autism. That's why, as we began our research on oxalate, I purposefully set out to test the raw ingredients being used commercially and in households for individuals on gluten and dairy-free diets. Our project discovered that there was a problem with buckwheat, amaranth, quinoa, and two late arrivals, chia seeds and hemp. We already knew oxalate was high in seeds like sesame seeds and poppy seeds, and also high in nuts like almonds which were now being made into milks for those on dairy-free diets. Soy is also high in oxalate, meaning soy has two problems—its opioid peptides and its oxalate level. In grains, most of the oxalate is in the bran, so the more "whole grain" a product is, the higher it will be in oxalate. Our listserve was literally flooded with individuals who found they got "sick" soon after they adopted what they thought was a "healthy diet". Another issue was the high levels of oxalate in chocolate and carob, which are used extensively in gluten-free "comfort foods". Last year, I attended a gluten-free expo in my city and picked up a cookbook full of new exciting recipes that were put together for this expo, and I saw that most of the recipes contained grains, or nuts or seasonings that were extremely high in oxalate. I couldn't help but wonder: Is this going to backfire for people, and will they recognize what is happening if by using these recipes and foods that they will find their health does not improve and may even get worse? In helping so many thousands of people reduce oxalate, our oxalate project has learned one thing clearly, and that is that giving someone a one page list of foods to avoid rarely successfully reduces oxalate in anyone. We have been told this most often by kidney stone patients who were given these lists by their doctors. Patients have told us hundreds of times that health improvements were not realized until they made this diet more like calorie counting. This is what we do in our support groups where people also monitor the contribution to their total oxalate level that comes from medium oxalate foods. This is why I would ask those reading this article to please seek our help if you wish to reduce oxalate, and do not strike out into the unknown on your own or confine yourself to the use of lists you might find on the Internet or at your doctor's office. Hundreds of Listmates have told us these lists had serious inadequacies and misinformation and little overlap with what they actually had been eating. We have also learned something else that is critically important. People who have been on an extremely high oxalate diet and then have reduced their diet's oxalate content too quickly, have gotten themselves in trouble. Some have ended up in emergency rooms in metabolic crisis with the doctors there unable to help them, because the doctors had never had training about why someone in this situation would get so sick. Even before our project started, we knew from studying the literature on those with primary hyperoxaluria, that when oxalate supply is reduced quickly by removing the liver that was putting out so much oxalate into their bodies, after replacing it with a normal liver, the amount of oxalate that suddenly began to leave the tissues of their body could potentially damage the replacement organ. Doctors have reported a very high death rate with these patients, which is reported to be much higher than death rates from other reasons for liver transplants. But what about what happens when reducing dietary oxalate? The food industry's recommendation of multiple fruits and vegetables has happened at the same as they began promoting many foods as super-foods and nutrient rich. Unfortunately, many of these same foods are so high in oxalate that they can keep someone from being able to retain and utilize minerals that are coming from other foods in the same meal. This can promote hyperabsorption of oxalate and increase risks of mineral imbalances. Our support groups have been deluged with individuals coming to us now with diets containing thousands of milligrams of oxalate putting their urine oxalate levels in ranges formerly seen only in the genetic hyperoxalurias. A low oxalate diet tries to keep the total oxalate load to between 40-60 mgs per day in adults As we said before, people who have been eating extremely high levels of oxalate need to reduce oxalate very slowly while the body adapts to the change. We have amassed a lot of experience with helping such individuals. The need for caution and more gradual change should not surprise us, because scientists are now telling us how quickly dietary changes can alter the function and composition of our microbial community and can also quickly alter cellular regulation of whatever enters and exits cells. These are compelling reasons to change the oxalate level slowly. Our website is www.lowoxalate.info. Our Yahoo group and our Facebook group are both called Trying_Low_Oxalates. We are partnering with non-profits and scientists from many fields around the world to fill in the missing science for a long list of disorders. Our work has gone far beyond autism, and we have been monitoring labwork on many conditions. We want to help make this dietary alteration as easy and safe as possible. We hope some of you readers will begin to get educated in this area. If you begin to reduce your oxalate, please let us know what reducing oxalate accomplishes for you. Since my early years in autism research, I have been convinced of one main principle. People with a condition will know their own bodies well. They are more likely to make important observations of change compared to a professional who comes in with too many preconceived expectations and has only a limited acquaintance with their subject's previous life. The first step in the scientific process really happens before scientific steps are put into use. The first "pre-step" is observation of something that does not fit old models. Frankly, after twenty years in research on autism, I don't believe the first step is best done by scientists and/or physicians. Why? Often someone new seeing a problem for the first time will notice aspects of that problem that people relying on old models will think is irrelevant and leave alone. That is why, to me, careful observations of hundreds and thousands of patients interacting can become the opportunity for forming new hypotheses that a scientist can later be recruited to test. This coordination of this volume of patient input was impossible before the internet allowed patients to find each other. But now, I think this is the most fertile field there is for making new scientific discoveries. Please, let's not confuse those two processes. First, we need to observe changes without layering expectations on what we see that comes from experience with only one type of patient. By looking at a broader diversity of patients, and discovering the overlap of their observations, we have a much better chance at noticing unexpected patterns that are significant. When people with no expectations of what ought to be ignored end up making the same observation time and again when they don't know each other, THEN you have something to legitimately research. At that point, the scientist can get involved with the second step, which is verifying the observations and seeing how widely they apply in one disorder or even more broadly. Using both steps, and both sets of eyes, and the marvelous ability to combine observations from thousands of individuals using the internet, we are now likely to begin to understand the complex role of oxalate in celiac disease and in many other disorders. From the author: If you have ever been diagnosed with an autoimmune disease and have been trying to lower oxalate, will you participate in the development of this science by filling out a survey? We would also like to find out whether reducing oxalate has affected your autoimmune condition. The link to our survey is here: https://www.surveymonkey.com/r/CMN5KK7 References: Baker PW, Bais, R, Rofe, AM Formation of the L-cysteine-glyoxylate adduct is the mechanism by which L-cysteine decreases oxalate production from glycollate in rat hepatocytes. Biochem. J. (1994) 302, 753-757 Capolongo G, Abul -Ezz S, Moe OW, Sakhaee K . Subclinical celiac disease and crystal-induced kidney disease following kidney transplant . Arn J Kidney Dis . 2012 Oct ;60(4) :662-7 . Halbrooks PJ, Mason AB , Adams TE, Briggs SK, Everse SJ . The oxalate effect on release of iron from human serum transferrin explained . J Mol Biol. 2004 May 21;339 (1):217-26. Kohman, E.F. Oxalic acid in foods and its behavior and fate in the diet. The Journal of Nutrition, 1940 18(3): 233-246. Konstantynowicz J, Porowski T, Zoch-Zwierz W, Wasilewska J, Kadziela -Olech H, Kulak W, Owens SC, Piotrowska-Jastrzebska J, Kaczmarski M. A potential pathogenic role of oxalate in autism . Eur J Paediatr Neurol . 2012 Sep;l6(5) :485-91 Monico, CG, Persson, M, Ford CG, Rumsby, G, Milliner, DS. Potential mechanisms of marked hyperoxaluria not due to primary hyperoxaluria I or II. Kidney International, 2002 Aug;62(2):392-400. PubMed PMID: 12110000 Nishijima S, Sugaya K, Hokama S, Oshiro Y, Uchida A, Morozumi M, Ogawa Y. Effect of vitamin B6 deficiency on glyoxylate metabolismin rats with and without glyoxylate overload. Biomedical Research, 2006 Jun; 27(3):P93-P98. Novartis Foundation Symposium 273, Epithelial anion transport in health and disease: The role of the SLC26 transporters family. John Wiley and Sons, Ltd. 2006. Rare Kidney Stone Consortium Mayo Clinic. http://www.rarekidneystones.org/hyperoxaluria/physicians.html Saccomani MD , Pizzini C, Piacentini GL, Boner AL , Peroni DG . Analysis of urinary parameters as risk factors for nephrol ithiasis in children with celiacdisease . J Urol. 2012 Aug ;188(2):566-70 . Speirs, M. The utilization of the calcium in various greens, The Journal of Nutrition, 1939 17(6), 557-564. Trivedi MS , Shah JS, Al-Mughairy S, Hodgson NW , Simms B, Trooskens GA, Van Criekinge W , Deth RC . Food-derived opioid peptides inhibit cysteine uptake with redox and epigenetic consequences . J Nutr Biochem . 2014 Oct ;25(10) :1011- 8 .
Monique Attinger posted an article in Spring 2016 IssueCeliac.com 06/07/2016 - The world of nutrition is currently obsessed with "super foods". Super foods are loosely defined as foods that are extremely high in nutrients – particularly antioxidants and vitamins – and which everyone is heartily advised to add to their diet. The problem with this approach is that, while focused firmly on nutrients, we are ignoring anti-nutrients! According to Wikipedia, an anti-nutrient is a compound in food that interferes with your absorption of other nutrients from a food. Most foods have varying amounts of anti-nutrients, toxins and other problematic compounds. A truly healthy diet will include weighing the good against the bad, while maintaining as much variety as possible. Once we have a clearer picture of how a food helps to support our nutrition, we can then decide how to include it in our diet and in what amount. Obviously, certain health conditions mean that certain foods are no longer healthful. For those with celiac disease, this means that grains with gluten in them are damaging to their health. It really doesn't matter how healthy wheat bran is for some – for celiacs, wheat bran is harmful. For those with allergies, you have a similar issue. Foods that may be healthy for some may not be for others. Another issue with food and health can be related to anti-nutrients. For instance, in the vegetarian world, we now hear more about phytate – often found in legumes – and how to reduce it in a plant-based diet. Salicylate is another anti-nutrient found in plant foods, and more people are finding that they need to consider this when choosing foods. Plants may also contain toxins, which are totally natural to the plant, but not good for you. Wikipedia indicates that a toxin is a substance that is directly poisonous, and capable of causing disease. For instance, some foods may contain naturally occurring cyanide compounds, or even arsenic in various forms. While we may not get enough to cause immediate problems, we certainly don't want to consume a lot of these toxins! Oxalate is another toxin present in many otherwise healthy foods. Oxalate poses many challenges for human health. It's a free radical. It promotes inflammation in your body. Because of its biochemistry, oxalate can be stored throughout your body, and can be particularly concentrated at the sites of previous injury, inflammation or surgery. Fundamentally, oxalate can be stored in tissues wherever the cells have taken it up. As a result, if you are someone who is absorbing too much oxalate from your diet, you can be contributing substantial stress to your body. Reducing the amount of oxalate in your diet cannot hurt you – you are reducing a totally non-nutritive substance for which the human body has no need and which contributes directly to health issues. However, reducing too many food types or nutrients in your diet can have negative impacts. The greater the variety in your diet, the better the chance that you are getting all your needed nutrients. The good news is that you can have a nutritious, high variety diet, and retain "super foods" in your diet which are high nutrition, gluten-free and low oxalate. Get Your Fiber The preponderance of processed foods in our diets can often leave us with hardly any fiber in our diet! Many gluten-free options are very low in fiber, and this can affect gut health. Fiber is not a direct nutrient for us per se – but it is a needed component that contributes to better gut flora and better health overall. Insoluble fiber adds bulk to the stool and promotes regularity. Most of us are not getting enough of this fiber, and as a result, can develop poor motility and constipation. Given that many whole grains are not good alternatives for those on a gluten-free diet, and the bran of many grains are actually high in oxalate, how can we get more healthy insoluble fiber? The good news is that one nutritional powerhouse is not only full of healthy insoluble fiber – it's also a plant source of Omega 3's. So a great solution to lack of insoluble fiber is flax seeds. Flax seeds can be eaten whole – but to really get the best benefits from this super food, it's best to grind your flax. Keep whole flax seeds in the freezer to preserve their freshness, and don't grind until just before using them. The recommended daily serving (which will also provide some soluble fiber) is two tablespoons. According to the Mayo Clinic, the right fiber goes much further than just regularity. If you increase soluble fiber, it can help reduce both blood sugar and cholesterol. Soluble fiber creates a gel-like material in the gut, and some research indicates that it may help to feed our gut bacteria. The benefits of soluble fiber are well known when it comes to cholesterol. The recommended food to get more soluble fiber is oats. However, whole oats are high in oxalate, and the oat bran has confusing test data. The solution? Psyllium! Pysllium is the medicinal ingredient in the popular product, Metamucil. Psyllium contains both soluble and insoluble fiber – and research on it shows that it can help to reduce cholesterol as well as normalize blood sugar. You can add it to baked products (but adjust the liquids), or sprinkle on foods. It's virtually tasteless – although you might find it does add some thickness or texture to liquids or foods. Fruits and vegetables are also good sources of both soluble and insoluble fiber and many are lower oxalate. Cabbages, lettuces, onions, cucumbers (with the skin) red bell peppers, orange, mango and grapes are all good low oxalate sources of fiber in your diet. Fruits There is no shortage of healthy options in fresh fruits that are also low oxalate, but the blueberry holds a special place among even the healthiest fruits. Research shows that blueberries are one of the most antioxidant rich foods available, and are included in most lists of super foods. Blueberries are one of the highest rated foods on the ORAC scale. The ORAC scale was developed by researchers at Tufts University, and is the measure of Oxygen Radical Absorbance Capacity (hence the abbreviation ORAC). What this really means for you is that the higher something ranks on the ORAC scale, the more antioxidants you are getting. Blueberries are stars on this scale, with an ORAC value of 4,669 per 100 grams, according to Superfoodly.com. Wild blueberries rank higher than cultivated ones – but you can't go wrong with any blueberry. Another fruit that ranks very high in ORAC is the lowly cranberry. While very tart (and difficult to eat raw), cranberries are second only to blueberries in antioxidant levels. To reduce the acidity of the fruit, and make them more palatable, cook with water and some honey. Cranberries are very easy to cook and make a lovely side dish for fattier meats like lamb. They aren't just for turkey anymore! Consuming these tangy fruits also help to contribute to bladder health. For nutrition on the go, turn to golden seedless raisins. While dark raisins are tasty treats, the golden seedless variety is both lower in oxalate and higher in antioxidants. In fact, golden seedless raisins actually have a higher ORAC score than fresh blueberries! Combine that with convenience and portability, and you have an easy way to get more antioxidants in your day. Raisins also make a great treat for kids, because of their sweetness. Is the apple a super food? Yes it is! Easy to purchase and pack for lunch, this popular fruit is full of quercetin, which protects cells from damage and is often recommended for those with allergies. Not only is it full of healthy antioxidants, it also has twice the fiber of other commonly eaten fruits, including peaches, grapes and grapefruit, according to the site EverydayHealth.com. Veggies When looking at veggies, many of the foods that are considered most healthy are also very high in oxalate. Everyone talks today about how healthy the sweet potato is for us: but did you know that a ½ cup of sweet potato can have over 90 mg of oxalate in it? For people trying to eat a low oxalate diet, a single serving would be more oxalate than they should consume in a whole day! However, while avoiding high oxalate foods, you do need to eat color and variety to get your needed nutrition. If you want a lower carbohydrate, orange veggie – consider the kabocha squash. Not only does this lower carb, low oxalate veggie work as a substitute for many recipes that require sweet potato, it also has a very good nutrient profile. Self Nutrition Data lists Vitamin A and Vitamin C as well as a good serving of Folate, in addition to good amounts of calcium, magnesium, phosphorus and potassium. Of course, you want other colors in your veggies as well – and green leafy veggies are particularly known for their nutrition. While spinach would be a bad choice because of extremely high oxalate, you have lots of other greens to choose from. Focus on lower oxalate varieties of kale, including purple kale. The website, The World's Healthiest Foods, lists kale as a food that can lower cholesterol (if steamed) as well as lower your risk of cancer. Of course, kale is part of the cruciferous vegetable family, and these foods have many anti-cancer benefits. Kale is an excellent source of Vitamin K (your blood clotting factor), as well as vitamin A, vitamin C, manganese, copper, B6 and others. Don't forget your other brassicas while you are focusing on kale! The cruciferous veggies also support our bodies natural detox processes, which is very valuable in today's world where we are exposed to many environmental toxins. Broccoli is another low oxalate brassica that is good for you, whether you are eating the mature broccoli heads, or feasting on broccoli sprouts. Note that broccoli sprouts do have an edge over their more mature cousins – they might just taste better, and given that they can be added to a sandwich for some satisfying crunch, might be easier to work into your daily diet. Research gives the sprouts a further edge in cancer risk reduction and some research indicates they may actually help to prevent stomach cancer. Another excellent leafy green is the lowly turnip green. Turnip greens are very high in calcium, and are even lower in oxalate than kale. A cup of cooked turnip greens will also get you more than 100% of the RDA for vitamin K. In addition, you'll get vitamin A, vitamin C, folate, copper, manganese, calcium, and vitamin E. Each serving will give you 15% of your daily requirement for B6. When thinking of deep red veggies, go for red cabbage. This versatile veggie is very low in oxalate, and that lovely red color means that it has even more protective phytonutrients, according to World's Healthiest Foods, than its green sibling! One serving of red cabbage delivers more than four times the polyphenols of green cabbage. Fats and Oils You can't read on super food nutrition anywhere and not run into the avocado. A great source of healthy monounsaturated fat, the avocado has also been linked to reduced risk of cancer, as well as lowered risk of heart disease and diabetes. While we think of avocados as a fatty food, they are actually a good source of fiber, with 11 to 17 grams of fiber per fruit! You'll also get a dose of lutein, an antioxidant recommended for eye health. Web MD says that lutein is a potent antioxidant, which is found in high concentrations in the eye. The combination of lutein and zeaxanthin (another antixodant) help to protect your eyes from damaging, high energy light. Some research indicates that a diet high in lutein and zeaxanthin may reduce the risk of cataracts by as much as 50%. Coconut oil is another excellent fat that can benefit our bodies in a host of ways. Doctor Oz lists a number of benefits, including supporting thyroid health and blood sugar control. This may be related to the form of saturated fat that is found in coconut oil, called lauric acid. Lauric acid is a medium-chain triglyceride. This kind of fat actually boosts immune system, and has antibiotic, antiviral and antifungal properties. It may also be a tool in your weight loss arsenal. A study in 2009 actually showed the eating 2 Tablespoons of coconut oil daily, allowed subjects to lose belly fat more effectively. Even better news for those who are following a low oxalate diet: both avocado and coconut oil have zero oxalate! Nuts, Seeds and Legumes Unfortunately, many foods in this category are high oxalate – and so won't qualify for our super food list. While you might be able to have a couple of walnut halves, or a similar amount of pecans, nuts are generally just to high to have in servings of more than 3-5 pieces. However, if you are looking for a superfood in this category, look no further than pumpkin seeds! Pumpkin seeds are an excellent source of vegetable-based protein, and are another portable food. A great snack for the health conscious can be made with raisins and pumpkin seeds – both are low oxalate, and the protein of the pumpkin seeds will help you to stay fuller longer. According to LiveStrong.com, a handful of pumpkin seeds will give you over 8 grams of protein. At the same time, pumpkin seeds are low in sugar, and provide you with fiber as part of the carbohydrate in them. You will also get vitamin A, vitamin B, vitamin K, thiamine, riboflavin, niacin, magnesium, calcium, iron, manganese, zinc, potassium, copper and phosphorus in that small and compact package! If pumpkin seeds don't qualify as a super food, it's hard to say what would! When it comes to legumes, many are stars for protein, but one of the best options is the red lentil. Lentils in general are easier to prepare than other types of legumes – they do not require the soaking and preparation time that many legumes do. At the same time, they are powerhouses of nutrition, with molybdenum, folate, fiber, copper, phosphorus and manganese all at more than 50% of your daily requirement. One cup of cooked lentils will also give you 36 % of your daily need for protein, according to World's Healthiest Foods. And all this nutrition is provided in a food that is virtually fat free and low in calories. You cannot go wrong! As an added benefit, some studies have found that eating high fiber foods like red lentils may reduce the risk of heart disease. The more fiber, the lower the risk of heart disease. Fish We are always hearing that we need to have more fish in our diets. It seems sometimes that not a week goes by when we are not hearing that we should be eating less meat, and getting less fat – with the suggestion that more fish would benefit us. When you think of the super food of fish, you have to think of salmon. Salmon is a fatty fish, and it's one of the best sources available for omega-3 fatty acids. In today's world of processed foods, omega-3's are one of the nutrients that we don't get enough of. Your best bet with salmon is to get wild-caught fish. Farmed salmon do not have the same nutrient profile, which may be related to the kind of food they are fed. Along with the decreased nutrient profile, studies have indicated that farmed salmon contains significantly higher concentrations of a number of contaminants (including PCBs, dieldrins, toxaphenes, dioxins and chlorinated pesticides) than wild caught salmon. World's Healthiest Foods states that a 4 ounce piece of Coho salmon will get you 55% of your daily requirements for omega-3 fats. On top of that, you'll get more than 50% of your daily requirement for vitamin B12, vitamin D, selenium, vitamin B3, protein and phosphorus, as well as other B vitamins and minerals. Omega-3 fatty acids will provide you a host of benefits, from reduction of inflammation, to better brain function. Omega-3 fat is also heart healthy, and can contribute to a reduced risk of heart attack, stroke, high blood pressure and other cardiovascular disease. Research indicates that eating salmon at least 2 to 3 times a week will give you the best benefits. Spice it up Spices can be a bit tricky, if you want to keep your oxalate low. Many spices – while tasty – are very high in oxalate! A great example of this is turmeric. A staple in most curry recipes, turmeric is extremely high oxalate – so while it has a reputation as a super food, it would not be a good choice if you are trying to keep your oxalate low. So what is your option if you love to eat foods spiced with turmeric? Well, the easiest approach is to stock your spice rack with a health food store supplement; cook with curcumin extract! While it may seem a bit odd at first, if you buy a curcumin extract (which is the extract from turmeric), you can get the flavor and leave the oxalate behind. While not technically a "food" when you cook with a supplement, you certainly get all the benefits of the original super food – turmeric – without the downside of oxalate. Another highly beneficial spice is cinnamon. Research clearly shows how helpful cinnamon is for managing blood sugar. However, ground cinnamon is an extremely high oxalate spice. So how can you get the flavor you want, while avoiding the oxalate? One solution is to cook with a cinnamon extract that you buy at the health food store! One brand known to be low oxalate is Doctor's Best. It is a dry extract in capsules – simply break open the capsules and use the contents in your dish. This allows you to get all the therapeutic benefits of the extract as well as the taste. You can also cook with essential oils and culinary oils – but use them carefully. Essential oils can be very strong and can irritate the tissues of the mouth and digestive tract. One drop of good quality essential cinnamon oil will replace as much as 1 tablespoon of ground cinnamon. Culinary oils are made for flavoring – follow the directions on the product that you buy. Either way, you will get the taste – and you avoid the oxalate. Enjoying Your Food! As with anyone who wants to eat a healthy diet full of super foods, the trick is to focus on the best nutrition, and get lots of variety. While some foods may not be as "super" as others, if you are making colorful meals, with healthful selections from across the spectrum, you'll be doing your body a favor with flavor! Where Does Oxalate Go? Once you have eaten oxalate, you have to excrete it through urine, feces or sweat. But what happens if you don't? A study on rats was able to trace where in the body a dose of oxalate remained. The scientists used a special carbon molecule – carbon 14 – in the oxalate they gave to the rats, so that they could find the oxalate wherever it went in the body. What they found is that if the oxalate was not excreted from the body, it was stored everywhere: 68% in the bones 9% in the spleen 8% in the adrenal glands 3% in the kidneys 3% in the liver 8% in the rest of the body These results are in direct opposition to conventional medical thinking, that oxalate only affects the kidneys. It clearly shows us that the whole body – but particularly the bones, key glands and detoxification organs – are all affected. This is another good reason to reduce the amount of oxalate in your diet! Is Spinach Really That Bad For You? A relatively simple study in the late 1930's looked at rats fed a diet that was only adequate in calcium. To bring the levels of calcium up, the rats were given spinach, equaling about 8% of their diet. While most of us think of spinach in terms of iron, it is also relatively high in calcium. The results of the study were shocking: 47. A high percentage of rats died between the age of 21 days and 90 days 48. The bones of the rats were extremely low in calcium (despite adding it to the diet through the spinach) 49. Tooth structure was poor and dentine of the teeth poorly calcified 50. For these animals, reproduction was impossible. Researchers concluded that not only did spinach not supply the needed calcium (because of the oxalate), but the spinach also rendered the calcium from other foods unavailable. What we know now is that oxalate is a mineral chelator – and rather than delivering minerals, it was robbing them from the rats. Getting Your Vitamin K Vitamin K is a very important nutrient. Life Extension indicates that new research from 2014 links vitamin K to longevity. In fact, the highest intakes of vitamin K reduced the likelihood of dying from any cause by 36%! So, you definitely want to get vitamin K in your diet. However, most of us think that we need to eat high oxalate greens – like spinach – in order to get good amounts of vitamin K. Nothing could be further from the truth! Kale, collards and turnip greens are all higher in vitamin K than spinach, and they have a fraction of the oxalate.
Susan Costen Owens posted an article in Summer 2016 IssueCeliac.com 07/29/2016 - Celiac is an autoimmune condition, and along with other autoimmune diseases, scientists are beginning to have a larger context for understanding what could be contributing to its immune dysregulation. In the last decades we've seen diseases becoming prevalent now that look very different from the diseases of our ancestors. The American Autoimmune and Related Diseases Association lists 159 autoimmune diseases on their website (1), but most of these diseases are very new. In recent years, scientists began to identify and explore a new complex that was identified within our cells and belongs to our immunological line of defense. This new player is part of innate immunity, which is also called cell-mediated immunity. This is our body's rapid responder, and its approach to immunity is more like hand to hand combat. Its role is surveillance, and it uses generalized markers to identify something as an enemy and something the immune system needs to defeat. It looks for evidence of infection from bacteria, fungi, viruses and parasites but it also analyzes cellular debris. It is looking for any sort of danger signal that conveys the message that life is not normal as it ought to be (2). This analysis can even include looking for changes in pH (3). The innate branch of the immune system is dependent on cells that are called phagocytes, and these cells like to engulf small pieces of things they encounter, in a process called phagocytosis. Often these cells will be breaking down those pieces it engulfs and then will returning the nutrition it contained back into the extracellular space. After fragments from outside are internalized, cells needed a way to decide if what was engulfed should lead to a stepped up immune response. That's why it is not surprising that scientists recently discovered a whole network of molecules internal to these cells that form a complex called an inflammasome. There are various types of inflammasome that cover different biological niches (4). What this means is that, in response to what is deemed an enemy, a phagocytic cell will gather together a distinctive list of parts to assemble into an inflammasome, and then that inflammasome will produce specific cytokines called IL-1 beta and IL-18. These chemical messengers can then go and recruit more help. In contrast, antibody mediated immunity is more like having an air defense. The antibodies made by this part of our immune system function more like missiles that are sent out to find a designated target. Vaccines are designed for the antibody side of the immune response. Future recognition of a previous invader involves selecting a piece of protein, called a peptide, that is large enough to recognize. This side of our immune response forms a memory of that peptide so that in the future, our cells will use that memory to recognize that we have seen that germ before. If the germ is recognized from a previous infection, then the immune system can respond very quickly and with more hands on deck. The piece of the intruder's identity that will be remembered is determined by our HLA type, and that is determined by a section of DNA on our sixth chromosome. The vulnerability to celiac disease is defined by the genes that are behind the formation of HLA-DQ2 and/or HLA-DQ8. Scientists have known for many years that these two branches of immunity compete with each other and need to stay in balance. The chemical immune messengers called cytokines will shift our immune response between a dominance of cell mediated or antibody-mediated immunity. Until very recently, all the attention in celiac was on the antibody mediated branch whose major decision-makers are T cells, but even T cells can form inflammasomes (5). Scientists are now studying the innate immune response to gluten. Our innate immunity relies on a specialized call type called a phagocyte. Cells of this type of include monocytes, macrophages, neutrophils, granuloctyes, mast cells, dendritic cells, osteoclasts and even migroglial cells in the brain. Phagocytic cells will incorporate debris that comes close to them into a vesicle, and that is a sort of bubble with liquid and other contents inside. This vesicle is taken into the cell through a process called endocytosis. After that, this type of cell will quickly process the contents of that vesicle probably much faster than other cell types. This competence is likely why this type of cell is given the job of surveillance for invaders. It is also is useful as a tool for recycling things from the outside that they take in. Scientists prefer to call this set of cells the professional phagocytic cells. Other cell types can be enlisted for the job of phagocytosis but they don't have that role as their main purpose. That is why this different set is called the non-professional phagocytic cells and they may also form inflammasomes but may need more stimulation. (6). Scientists in the last decade have done experiments to learn how inflammasomes work. These intracellular immune complexes are assembled often in response to exposures to a type of molecule called a lipopolysaccharide that can be detected after engulfing the cell membranes of invading organisms. There are many other triggers, all recognized by their ability to tell us when something inside us is not as it should be. ATP, our body's energy molecule, when it is identified as coming in from the outside, can be a trigger for the inflammasome. Engulfing this sort of molecule suggests to our phagocytes that cell death events may have occurred in the environment of that cell (7). Some of our cells have been found to extrude nucleotides in self-defense, because leftovers from that kind of event may tell the inflammasome machinery that the cell is encountering a dangerous situation (8). This system recognizes that certain pathogens create holes in cell walls, so when a phagocyte encounters evidence of damaged membranes with holes in them, that alone can trigger a cell danger response that enlists inflammasomes. That means two popularly used medicines that kill fungus by inserting holes in their cells, Nystatin and Amphotericin B, have by themselves been found to create this danger signal even when there is no infectious agent. Doctors and lay people need to know that many signs that are usually associated with an infection, including fever, can occur when there is nothing infectious involved (9). Another inflammasome trigger is excess alcohol which can be very damaging when it triggers inflammasomes in the nervous system. (10) Another concern is environmental contaminates like asbestos and silica which have been studied the most when they are inhaled. (11) Crystals of uric acid associated with gout or other cell debris can also trigger the inflammasome, as can crystals of oxalate, which may be important to celiac disease since scientists have found higher levels of oxalate in celiac sprue. These crystals must reach a critical concentration to generate this cell danger mechanism in phagocytic cells (12). In the past, nobody really was aware that oxalate could have a major effect on the immune system outside of what it does in the kidneys. Scientists for so many years thought the kidney alone contained cells that oxalate could influence. That's why other cell types were not studied. At least now, we realize this narrow focus had been based on some premature conclusions. We should have known to look more broadly because there was so much evidence from Primary Hyperoxaluria, a genetic disorder where a defective liver produces oxalate that travels to the whole body, creating a condition called oxalosis. That's how we know that oxalate goes all over the body. For the longest time, nobody was measuring oxalate outside of kidney disease, even though there were a few exceptions, like in people after bariatric surgery, and in celiac sprue and in cystic fibrosis, and eventually, in autism (13). Because there already was a literature about oxalate in celiac sprue, when our project began, we started informing the public about these links on our website, www.lowoxalate.info. More recently we have written a series of articles about oxalate in this journal, discussing the science, and also practical issues about how to reduce oxalate while on a gluten free diet. That was working with knowledge we had then, but now we know that this issue of inflammasomes has been a part of the story we didn't know, but it holds great promise of possibly addressing why there could be complications in celiac sprue that do not resolve by merely going gluten free. Another trigger for the inflammasome is homocysteine (14). The pathway to recycle homocysteine back to methionine is called remethylation, and this process requires both methylcobalamin and the folic acid cycle. Others on internet groups have brought attention to polymorphisms in one of the relevant enzymes, called MTHFR. This system is also tied to the process of making sulfate, taurine and glutathione, because homocysteine can be routed that direction when the body is trying to resolve oxidative stress. Many of these steps require B6, and heme is also needed to direct homocysteine towards transsulfuration. The issue of excess homocysteine may prove to be more important to our non-professional phagocytic cells that are found lining our blood vessels, because these same vessels can also take up oxalate, creating a condition of vascular swelling called livedo reticularis (15). Issues with both homocysteine and oxalate have been associated with atherosclerosis (16). Did your child's pediatrician recommend giving your child Tylenol before his immunizations to make him more comfortable about his body's reaction to his shots? Scientists have now found that Tylenol not only depletes our body's ability to deal with the oxidative stress from immunization, but it also turns on the inflammasome (17). The inflammasome will skew immune defense away from Th2 adaptive immunity, and that is unfortunate, in this case, because the process of developing a Th2 response was the whole point of giving a child a vaccine. Our vaccines are designed to contain adjuvants that skew the immune response in the Th2 direction (18) but some adjuvants may not be working as expected (19). Researchers sometimes look for the evidence that someone has developed antibodies before they will call an immunization a success. That test will ordinarily not be ordered by a pediatrician, but instead, a child will simply later be given, by default, a booster shot. Is there any chance the recommendation of Tylenol or other inflammasome activators could have impaired the antibody response in some children? Certainly, the new research on inflammasomes might suggest that in children who fail to make antibodies after a vaccine, a look at what is happening with innate immunity could be in order before assuming that these systems are working normally. Are doctors testing antibody titres or doing other immune testing in children with celiac sprue? This may be more important if such a child has developed another autoimmune condition. Has gluten had other ways of affecting the immune response? We have known that gluten and proteins from milk, soy, and even spinach will form opioid peptides as they are broken down. Like other opiates, these active peptides can be addictive and would be able to skew an immune response (20).Opioids can also paradoxically activate inflammasomes in the spinal column which then may provoke, amplify, and prolong pain. (21) Other work showed us that activation at the same opioid receptors that drugs use can limit our absorption of the amino acid cysteine. This amino acid is needed by our bodies in order to provide glutathione, the primary cellular antioxidant that protects us from oxidative stress, and this is especially important to save us from neurodgeneration (22). Why is that important? The formation of glutathione can calm down a mitochondrion that is upset enough for it to be generating reactive oxygen species (ROS). Unfortunately, scientists recently learned that the ROS produced by a mitochondrion under such stress will also trigger the inflammasome. Having adequate glutathione is especially important when our bodies are coping with the demands of immune activity, as during illness or after immunization. Unfortunately, oxalate at those times may compete with glutathione for entry into the mitochondrion at the mitochondrial dicarboxylate carrier (23). Until very recently, we did not know that partially digested pieces formed from gliadin could trigger the formation of the inflammasome. This occurred more in peripheral blood mononuclear cells (PBMCs) from people with celiac sprue compared to healthy donors (24). The people who did this research may not have known that people with celiac tend to be higher in oxalate than other people, and they also may not have known that oxalate by itself has been found to trigger the formation of the inflammasome. People with celiac may need to be careful about avoiding both triggers for inflammasome formation. In a different context, another group of scientists discovered that PBMC's exposed to titanium salts made from oxalate caused immunotoxicity when other salts of titanium did not produce that toxic effect. That experiment tells us that oxalate does enter the type of cell that was also found to respond in celiac disease to these digests of gliadin by formation of the inflammasome (25). The well-studied vulnerability of individuals with celiac to antibody mediated effects of gliadin came from the adaptive arm of our immunity. The HLA type is definitely known to be relevant there, but it would not be relevant to an issue of cell-mediated immunity. That is why it is a puzzle that the authors of this study did not control for oxalate by matching the control and celiac subjects for the oxalate content of their cells. The differences they saw in response to the gliadin digest may have required higher levels of oxalate in those cells. Do we know? If that could be the case, then it becomes possible that the response they recorded in celiac cells might also happen in those who are higher in oxalate for other reasons, but who lack the HLA risk genes that are definitional of celiac. We simply cannot tell if the risk of inflammasome activation in their experiment involved having the oxalate content of these cells also working in some kind of synergism with gluten. It is important to note that here we are talking about oxalate that this type of cell may have accumulated earlier in its life or during its time in the blood. Here we are not talking about oxalate that someone may have just eaten. It is possible that an inflammasome-mediated function could explain why there are so many people who don't have celiac disease discovering that removing gluten from the diet makes them feel better. The academic community and others are still having a hard time believing this story (26), and cannot understand the recent popularity of gluten free foods in the general population. A different reason for thinking about a possible synergism between a gluten free and a reduced oxalate diet came from a recent poll done by the Oxalate Project at www.lowoxalate.info. Those results revealed that the majority of those who reported positive effects in their autoimmune disease by reducing oxalate had been extremely high in oxalate before they reduced oxalate. Curiously, 58% of those responding to the poll said they were also gluten free, but only 16% had celiac sprue. Those who were both gluten free and low oxalate reported a 10% higher positive effect from reducing oxalate than those who were not also gluten free. That could be important. Many scientists still think a standard American diet will keep oxalate below 200 mgs a day, but 84% of the individuals answering that poll said that they started out with levels of oxalate over 300 mgs a day. Recent changes in eating habits for high oxalate foods may have been the result of powerful advertising that has been telling people that high oxalate foods are the healthiest foods available. Anonymous poll data has no way to be verified, and that fact keeps us from assuming that we can derive information from this poll about oxalate's role (if any) in contributing to their autoimmune condition. Even so, the poll told us that out of all respondents, 73% reported a positive effect in their autoimmune condition by reducing oxalate, but those with celiac sprue (some who had other autoimmune conditions) did much better. 88% of them reported a positive effect on their autoimmune condition. That was actually a higher percentage than what was recorded for any of the other autoimmune conditions. Does that mean that it might be important for autoinflammatory processes to be careful about both gluten and oxalate? (27) We may learn the answer to that question as more people with these issues try both dietary changes together. Some scientists now are generating data that they feel supports the idea that excessive activity of inflammasomes could be related to the etiology of autoimmune disease (28). The changes that the inflammasome makes to our bodies can be harsh, and in fact, some scientists studied sepsis in animals and found that just by blocking inflammasome activity by various inhibitors, they could save those animals from a certain death. The irony is that the animals were still infected, but survived anyway. That means that what had been killing them was their immunological response to infection instead of the infection itself. This type of research is still very new, but it may change some of our assumptions (29). What interventions have scientists found that will suppress inflammasome activity? The good news is that a lot of their research has involved supplements that anyone can buy in a health food store, and some people were already using them for different reasons. One of those items is resveratrol. When it was first studied, it seemed to have been made out of red wine, mostly, but our project has discovered that commercially, the usual product is made from an herb called Japanese knotwood, which is known to be high in oxalate (30). The Oxalate Project has not yet tested the oxalate content of commercially available brands of resveratrol to see how much oxalate ends up in a capsule, but that testing is on its agenda. The supplement quercitin is also an inflammasome inhibitor (31). CoQ10 is another supplement that has become widely available in drug stores and health food stores because it is needed to correct a mitochondrial problem created by statin drugs. Fortunately, CoQ10 also inhibits the inflammasome, mainly by keeping the mitochondrion happier and better protected from the need to generate reactive oxygen species (32). A popular source of sulfur called MSM (methylsulfonylmethane) also was found to inhibit inflammasomes (33). So has its close cousin DMSO, a solvent that was once used as a delivery system for secretin, when it was proposed as a treatment for autism (34, 35). Another exciting inhibitor is 3-hydroxybutyrate, which is one of the two ketones (along with acetoacetate) that our bodies make in ketosis (36). Ketosis occurs when the body is not getting enough energy from carbohydrate, and it switches into a mode of burning fat, and that produces these ketones. Some people will try to induce this switch in metabolism on purpose, like those dealing with seizures who find the seizures are controlled with a ketogenic diet. If the change that this ketogenic diet accomplished was due to down regulation of inflammasome activity, that might bring new hope or strategies to mind for individuals where this diet treatment by itself failed. Such individuals may have had a different environmental component that was still activating inflammasomes in spite of their use of the use of the ketogenic diet. This mechanism may point to yet another reason that obesity, which may have come from excess consumption of carbohydrate, has been linked with inflammasome activation (37). We can hope that more investigation of other activators and other inhibitors for those with seizures might yield better success. Also, the association with ketosis may explain a previously overlooked benefit experienced by people who were exercising the discipline of fasting…the age-old tradition that comes from many cultures. These traditions are more striking when realizing that obesity can activate inflammasomes and inflammasomes are thought to be behind the roots of metabolic syndrome and diabetes (38, 39). Pharma does have some drugs already in its cabinet which scientists have found will inhibit inflammasomes. There are probably more such drugs in the pipeline and we may soon hear advertisements for this new class of drugs. Our Oxalate project has already begun to hear of some doctors and hospitals using the over the counter inhibitors resveratrol or coQ10 to successfully protect patients who were at risk for developing sepsis. More research obviously needs to be done in this area and this new frontier has become very attractive to scientists. One of the first big questions they may need to ask is whether our health care protocols in Western medicine have led to over-stimulating this arm of immunity by emphasizing killing strategies with antimicrobial therapies or other drugs that may leave crystals or other debris behind. Why might that have been a problem? Phagocytes are upset about cellular debris and disrupted membranes. Some scientists have been finding that our bodies may stay healthier by tolerating some infections rather than experiencing the excessive immune activity that comes from activating inflammasomes. It will take a long time for some of these scientific ideas to trickle down and begin persuading doctors to make changes in their prescribing habits for antibiotics and other antimicrobials. Some doctors and other practitioners are already finding that inflammasome inhibitors could be an appropriate adjunct therapy during antibiotics. Of course, since this is such a new scientific area to study, it may take years before proper clinical studies can be done to address all these issues. In the meantime, it seems wise for anyone prone to autoimmune disease to avoid triggers for inflammasomes that are easy to avoid. This would include things like being overweight, eating foods that encourage uric acid formation (and the risks known for gout). It could include situations that encourage the body to make oxalate and that could include deficiencies of B6 or thiamine, or excess use of Vitamin C. It could come from excess dietary oxalate. We also need to consider the use of drugs or supplements that are known to form crystals in blood, or Tylenol, or antifungals that punch holes in cell membranes. We need to be vigilant about our status for homocysteine. We need to be careful about our level of consumption of alcoholand our exposureto other environmental contaminants. In time, we will learn of many other triggers. If there is a suspicion that inflammasomes are related to a disease process that we find in our bodies, then we should at least think about using one of the over the counter and safe and well-studied inflammasome suppressors. As the research continues, we can hope that scientists studying in this area will show us more ways to dial down the frequency and the unpleasant symptoms and other consequences of autoimmune disease and autoinflammation. References: 1. (http://www.aarda.org/autoimmune-information/list-of-diseases/) 2. Doria A, Zen M, Bettio S, Gatto M, Bassi N, Nalotto L, Ghirardello A, Iaccarino L, Punzi L. Autoinflammation and autoimmunity: bridging the divide. Autoimmun Rev. 2012 Nov;12(1):22-30. doi: 10.1016/j.autrev.2012.07.018. Epub 2012 Aug 2. Review. PubMed PMID: 22878274. 3. Rajamäki K, Nordström T, Nurmi K, Åkerman KE, Kovanen PT, Öörni K, Eklund KK. Extracellular acidosis is a novel danger signal alerting innate immunity via the NLRP3 inflammasome. J Biol Chem. 2013 May 10;288(19):13410-9. doi: 10.1074/jbc.M112.426254. Epub 2013 Mar 25. PubMed PMID: 23530046; PubMed Central PMCID: PMC3650379. 4. Kummer JA, Broekhuizen R, Everett H, Agostini L, Kuijk L, Martinon F, van Bruggen R, Tschopp J. Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. J Histochem Cytochem. 2007 May;55(5):443-52. Epub 2006 Dec 12. PubMed PMID: 17164409. 5. Arbore G, West EE, Spolski R, Robertson AA, Klos A, Rheinheimer C, Dutow P, Woodruff TM, Yu ZX, O'Neill LA, Coll RC, Sher A, Leonard WJ, Köhl J, Monk P, Cooper MA, Arno M, Afzali B, Lachmann HJ, Cope AP, Mayer-Barber KD, Kemper C. T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4âº T cells. Science. 2016 Jun 17;352(6292):aad1210. doi: 10.1126/science.aad1210. PubMed PMID: 27313051. 6. Paoletti, R.; Notario, A.; Ricevuti, G., eds. (1997). Phagocytes: Biology, Physiology, Pathology, and Pharmacotherapeutics. New York: The New York Academy of Sciences. ISBN 1-57331-102-2. 7. Kim JJ, Jo EK. NLRP3 inflammasome and host protection against bacterial infection. J Korean Med Sci. 2013 Oct;28(10):1415-23. doi: 10.3346/jkms.2013.28.10.1415. Epub 2013 Sep 25. Review. PubMed PMID: 24133343; PubMed Central PMCID: PMC3792593. 8. Coutinho-Silva R, Ojcius DM. Role of extracellular nucleotides in the immune response against intracellular bacteria and protozoan parasites. Microbes Infect. 2012 Nov;14(14):1271-7. doi: 10.1016/j.micinf.2012.05.009. Epub 2012 May 23. Review. PubMed PMID: 22634346; PubMed Central PMCID: PMC4110109. 9. McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, Waterhouse CC, Beck PL, Muruve DA, Kubes P. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science. 2010 Oct 15;330(6002):362-6. doi: 10.1126/science.1195491. Erratum in: Science. 2011 Mar 25;331(6024):1517. PubMed PMID: 20947763. 10. Lippai D, Bala S, Petrasek J, Csak T, Levin I, Kurt-Jones EA, Szabo G. Alcohol-induced IL-1β in the brain is mediated by NLRP3/ASC inflammasome activation that amplifies neuroinflammation. J Leukoc Biol. 2013 Jul;94(1):171-82. doi: 10.1189/jlb.1212659. Epub 2013 Apr 26. PubMed PMID: 23625200; PubMed Central PMCID: PMC3685015. 11. Dostert C, Pétrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica.Science. 2008 May 2;320(5876):674-7. doi: 10.1126/science.1156995. Epub 2008 Apr 10. PubMed PMID: 18403674; PubMed Central PMCID: PMC2396588. 12. Petrasek J, Iracheta-Vellve A, Saha B, Satishchandran A, Kodys K, Fitzgerald KA, Kurt-Jones EA, Szabo G. Metabolic danger signals, uric acid and ATP, mediate inflammatory cross-talk between hepatocytes and immune cells in alcoholic liver disease. J Leukoc Biol. 2015 Aug;98(2):249-56. doi: 10.1189/jlb.3AB1214-590R. Epub 2015 May 1. PubMed PMID: 25934928; PubMed Central PMCID: PMC4501673. 13. Owens SC. What is the Relationship Between Oxalate and Celiac Disease?. Journal of Gluten Sensitivity. Spring 2015; 14(2):1-11. 14. Xi H, Zhang Y, Xu Y, Yang WY, Jiang X, Sha X, Cheng X, Wang J, Qin X, Yu J, Ji Y, Yang X, Wang H. Caspase-1 Inflammasome Activation Mediates Homocysteine-Induced Pyrop-Apoptosis in Endothelial Cells. Circ Res. 2016 May 13;118(10):1525-39. doi: 10.1161/CIRCRESAHA.116.308501. Epub 2016 Mar 22. PubMed PMID: 27006445; PubMed Central PMCID: PMC4867131. 15. Shih HA, Kao DM, Elenitsas R, Leyden JJ. Livedo reticularis, ulcers, and peripheral gangrene: cutaneous manifestations of primary hyperoxaluria. Arch Dermatol. 2000 Oct;136(10):1272-4. PMID: 11030785. 16. Faure V, Dou L, Sabatier F, Cerini C, Sampol J, Berland Y, Brunet P, Dignat-George F. Elevation of circulating endothelial microparticles in patients with chronic renal failure. J Thromb Haemost. 2006 Mar;4(3):566-73. Epub 2005 Dec 23. PubMed PMID: 16405517. 17. Jaeschke H, Williams celiac disease, Ramachandran A, Bajt ML. Acetaminophen hepatotoxicity and repair: the role of sterile inflammation and innate immunity. Liver Int. 2012 Jan;32(1):8-20. doi: 10.1111/j.1478-3231.2011.02501.x. Epub 2011 Mar 14. Review. PubMed PMID: 21745276; PubMed Central PMCID: PMC3586825. 18. Quandt D, Rothe K, Baerwald C, Rossol M. GPRC6A mediates Alum-induced Nlrp3 inflammasome activation but limits Th2 type antibody responses. Sci Rep. 2015 Nov 25;5:16719. doi: 10.1038/srep16719. PubMed PMID: 26602597; PubMed Central PMCID: PMC4658484. 19. Franchi L, Núñez G. The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity. Eur J Immunol. 2008 Aug;38(8):2085-9. doi: 10.1002/eji.200838549. PubMed PMID: 18624356; PubMed Central PMCID: PMC2759997. 20. Trivedi MS, Shah JS, Al-Mughairy S, Hodgson NW, Simms B, Trooskens GA, Van Criekinge W, Deth RC. Food-derived opioid peptides inhibit cysteine uptake with redox and epigenetic consequences. J Nutr Biochem. 2014 Oct;25(10):1011-8. doi: 10.1016/j.jnutbio.2014.05.004. Epub 2014 Jun 6. PubMed PMID: 25018147; PubMed Central PMCID: PMC4157943. 21. Grace PM, Strand KA, Galer EL, Urban DJ, Wang X, Baratta MV, Fabisiak TJ, Anderson ND, Cheng K, Greene LI, Berkelhammer D, Zhang Y, Ellis AL, Yin HH, Campeau S, Rice KC, Roth BL, Maier SF, Watkins LR. Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation. Proc Natl Acad Sci U S A. 2016 Jun 14;113(24):E3441-50. doi: 10.1073/pnas.1602070113. Epub 2016 May 31. PubMed PMID: 27247388; PubMed Central PMCID: PMC4914184. 22. Johnson WM, Wilson-Delfosse AL, Mieyal JJ. Nutrients. Dysregulation of glutathione homeostasis in neurodegenerative diseases.2012 Oct 9;4(10):1399-440. doi: 10.3390/nu4101399. Review.PMID:23201762 23. Chen Z, Lash LH. Evidence for mitochondrial uptake of glutathione by dicarboxylate and 2-oxoglutarate carriers. J Pharmacol Exp Ther. 1998 May;285(2):608-18. PubMed PMID: 9580605. 24. Palová-Jelínková L, DáÅˆová K, Drašarová H, DvoÅ™ák M, Funda DP, Fundová P, Kotrbová-Kozak A, ÄŒerná M, Kamanová J, Martin SF, Freudenberg M, TuÄková L. Pepsin digest of wheat gliadin fraction increases production of IL-1β via TLR4/MyD88/TRIF/MAPK/NF-κB signaling pathway and an NLRP3 inflammasome activation. PLoS One. 2013 Apr 29;8(4):e62426. doi: 10.1371/journal.pone.0062426. Print 2013. PubMed PMID: 23658628; PubMed Central PMCID: PMC3639175. 25. Di Giampaolo L, Di Gioacchino M, Ponti J, Sabbioni E, Castellani ML, Reale M, Toto E, Verna N, Conti P, Paganelli R, Boscolo P. "In vitro" comparative immune effects of different titanium compounds. Int J Immunopathol Pharmacol. 2004 May-Aug;17(2 Suppl):115-22. PubMed PMID: 15345202. 26. Rakhimova M, Esslinger B, Schulze-Krebs A, Hahn EG, Schuppan D, Dieterich W. In vitro differentiation of human monocytes into dendritic cells by peptic-tryptic digest of gliadin is independent of genetic predisposition and the presence of celiac disease. J Clin Immunol. 2009 Jan;29(1):29-37. doi: 10.1007/s10875-008-9228-x. Epub 2008 Aug 12. PubMed PMID: 18696220. 27. Owens SC, de La Garza P. Autoimmunity Survey. [Other]. Palo Alto, California, USA: Survey Monkey, Inc.; 2016 March. Available from: www.surveymonkey.com. 28. Shaw PJ, McDermott MF, Kanneganti TD. Inflammasomes and autoimmunity. Trends Mol Med. 2011 Feb;17(2):57-64. doi: 10.1016/j.molmed.2010.11.001. Epub 2010 Dec 14. Review. PubMed PMID: 21163704; PubMed Central PMCID: PMC3057120. 29. Sui DM, Xie Q, Yi WJ, Gupta S, Yu XY, Li JB, Wang J, Wang JF, Deng XM. Resveratrol Protects against Sepsis-Associated Encephalopathy and Inhibits the NLRP3/IL-1β Axis in Microglia. Mediators Inflamm. 2016;2016:1045657. doi: 10.1155/2016/1045657. Epub 2016 Jan 26. PubMed PMID: 26924896; PubMed Central PMCID: PMC4746398. 30. Chen H, Tuck T, Ji X, Zhou X, Kelly G, Cuerrier A, Zhang J. Quality assessment of Japanese knotweed (Fallopia japonica) grown on Prince Edward Island as a source of resveratrol. J Agric Food Chem. 2013 Jul 3;61(26):6383-92. doi: 10.1021/jf4019239. Epub 2013 Jun 19. PubMed PMID: 23742076. 31. Hu QH, Zhang X, Pan Y, Li YC, Kong LD. Allopurinol, quercetin and rutin ameliorate renal NLRP3 inflammasome activation and lipid accumulation in fructose-fed rats. Biochem Pharmacol. 2012 Jul 1;84(1):113-25. doi: 10.1016/j.bcp.2012.03.005. Epub 2012 Mar 16. PubMed PMID: 22426011. 32. Cordero MD, Alcocer-Gómez E, Culic O, Carrión AM, de Miguel M, Díaz-Parrado E, Pérez-Villegas EM, Bullón P, Battino M, Sánchez-Alcazar JA. NLRP3 inflammasome is activated in fibromyalgia: the effect of coenzyme Q10. Antioxid Redox Signal. 2014 Mar 10;20(8):1169-80. doi: 10.1089/ars.2013.5198. Epub 2013 Sep 19. PubMed PMID: 23886272; PubMed Central PMCID: PMC3934515. 33. Ahn H, Kim J, Lee MJ, Kim YJ, Cho YW, Lee GS. Methylsulfonylmethane inhibits NLRP3 inflammasome activation. Cytokine. 2015 Feb;71(2):223-31. doi: 10.1016/j.cyto.2014.11.001. Epub 2014 Nov 21. PubMed PMID: 25461402. 34. Ahn H, Kim J, Jeung EB, Lee GS. Dimethyl sulfoxide inhibits NLRP3 inflammasome activation. Immunobiology. 2014 Apr;219(4):315-22. doi: 10.1016/j.imbio.2013.11.003. Epub 2013 Nov 22. PubMed PMID: 24380723. 35. Lamson DW, Plaza SM. Transdermal secretin for autism - a case report. Altern Med Rev. 2001 Jun;6(3):311-3. PubMed PMID: 11410075. 36. Netea MG, Joosten LA. Inflammasome inhibition: putting out the fire. Cell Metab. 2015 Apr 7;21(4):513-4. doi: 10.1016/j.cmet.2015.03.012. PubMed PMID: 25863243. 37. Shao BZ, Xu ZQ, Han BZ, Su DF, Liu C. NLRP3 inflammasome and its inhibitors: a review. Front Pharmacol. 2015 Nov 5;6:262. doi: 10.3389/fphar.2015.00262. eCollection 2015. Review. PubMed PMID: 26594174; PubMed Central PMCID: PMC4633676. 38. Jin C, Flavell RA. Innate sensors of pathogen and stress: linking inflammation to obesity. J Allergy Clin Immunol. 2013 Aug;132(2):287-94. doi: 10.1016/j.jaci.2013.06.022. Review. PubMed PMID: 23905917. 39. Lee HM, Kim JJ, Kim HJ, Shong M, Ku BJ, Jo EK. Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes. 2013 Jan;62(1):194-204. doi: 10.2337/db12-0420. Epub 2012 Oct 18. PubMed PMID: 23086037; PubMed Central PMCID: PMC3526026.