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Good morning, everybody. Hope you all had a great holiday weekend. Today we’re back in the saddle, and I’m getting in touch to ask a favor….
Specifically, I’m asking you to tell me a bit about yourself—where you are in your health journey, what challenges you, and what brings you (and keeps you coming back) to Mark’s Daily Apple. I’d like to use your feedback in this brief survey to help push MDA into new territory—to make a resource that better engages you and supports your interests.
Will you take just a few minutes with me today?
Over the years you’ve gotten to know me here on the blog, and I’ve loved meeting many of you through events like PrimalCon, Paleo f(x), and Primal Health Coach gatherings—or through your emails and letters. I’ve enjoyed answering as many of your questions as I can here and continuing the dialogue with you on the comment board as well as in our Facebook group and on our Instagram page. All of the success stories and progress photos you’ve sent over the years are truly inspiring and keep me doing what I do—so keep them coming!
For those of you who may be new to our community — first, welcome — or those who may have been less outspoken in comments, we’d love to hear more from you. Even if you feel like you’ve shared a lot about yourself over the years, I encourage you to take the survey as well. My hope is that this reader survey my staff and I have created will tell me more about what you want to read, what you find difficult, and why YOU do what you do.
And as a thank you for your time, you’ll receive a coupon for $10 off any purchase of $50 or more in our Primal Blueprint store.
Will you share your story with us? Complete the survey HERE.
Thanks for being here, and I’m grateful for your help today. Grok on, everybody.
In a previous post, we looked at the development of immune tolerance (the body’s lack of reaction to antigens that could potentially trigger an immune response) in the context of children (see “Development of Immune Tolerance in Children”). Research shows that early introduction of very small amounts of the most common allergens (like gluten, dairy, peanuts, and fish) can help prevent food allergies from developing later on, especially when those foods are introduced in conjunction with probiotics and proteins delivered through breast milk. But, what about adults?! There have been concerns that diets eliminating wheat, dairy, peanuts, and other allergenic foods (as happens on strict Paleo and AIP) could cause us to lose tolerance to things we previously could handle. As a result, we might wonder if we should keep eating at least small amounts of allergenic foods on a regular basis to prevent this from happening!
Unfortunately, immune tolerance in adults doesn’t receive as much discussion as it does in children, so it can be hard to know how to approach this issue. Should we eat a few bites of bread or peanut butter each week to help maintain immune tolerance, even in an otherwise Paleo or AIP diet? Or, would it do more harm than good to keep these things in our diet, especially while we’re trying to heal? Let’s look at what the science has to say!
First of all, let’s define our terms! When we find ourselves reacting negatively to the foods we eat (especially to foods we once handled just fine!), it’s important to distinguish between an allergy, intolerance, and sensitivity. These words are sometimes thrown around interchangeably, but they all mean very different things.
Food allergies are immune reactions where the body produces Immunoglobulin E (IgE) antibodies against a food protein, leading to a histamine release from two types of immune cells (mast cells and basophils). This results in allergy symptoms like hives, rashes, abdominal pain, bloating, sneezing, coughing, wheezing, shortness of breath, runny nose, red or itchy eyes, skin flushing, or swelling of the lips, nasal tissues, eyes, ears, face, tongue, and/or throat. These reactions can range from subtle (like mild seasonal allergies) to dramatic (as with anaphylaxis, a life-threatening reaction characterized by hives, severe swelling, trouble breathing, and shock). Allergies occur very quickly after ingesting the triggering food.
Food intolerances are reactions to food that aren’t immune in nature (that is, they don’t trigger antibody production). In some cases, like with lactose intolerance, food intolerances are caused by enzyme deficiencies that prevent us from properly breaking down food components. Unlike allergies, food intolerances tend to have side effects that are primarily gastrointestinal (cramping, bloating, diarrhea, upset stomach, and/or gas), and that, unlike severe allergies, aren’t life-threatening. Symptoms can also take a longer time to appear, anywhere from several hours to several days!
Food sensitivities have a less consistent definition in the medical field, but they generally involve a food-directed immune reaction other than an IgE response (other responses include IgG, IgA, or IgM antibody production). An immune reaction of this nature can result from leaky gut, which allows proteins from virtually any food we eat to cross the gut barrier, interact with the immune system, and cause unpleasant symptoms (see What Is A Leaky Gut? (And How Can It Cause So Many Health Issues?)). Other mechanisms that result in adverse food reactions include through the effects of severe gut dysbiosis (production of bacterial metabolites, for example, may be the cause of a sensitivity), or from an inability to process or metabolize a substance (which can cause inflammation, damage to the gut, strain on the liver, or damage to other tissues). Like food intolerances, non-IgE immune reactions (such as salicylate sensitivity, histamine sensitivity, and sulfite sensitivity) can produce gastrointestinal symptoms, but often include allergy-like reactions as well, such as itchy skin, hives, rashes, headaches, and low blood pressure. (For information on how to get tested for food sensitivities, see “Guest Post by Dr. Kellie Ferguson: Food Sensitivity Testing – Let’s Talk About Your Options!”)
Why is it important to distinguish between all these reactions? Because their causes and treatments are very, very different! True food allergies are unlikely to be either caused or reversed by adopting a different diet, although in some cases, Paleo or AIP may help reduce the severity of symptoms (through providing nutrients important for immune regulation). Non-IgE-mediated intolerances, on the other hand, tend to be much more transient and reversible with dietary modifications. If we avoid the foods we’re intolerant to and take measures to restore our gut barrier function, we can often re-introduce those foods later on without adverse reactions. (For example, with careful avoidance, IgG antibodies against food disappear within three months to two years (depending on how high they were initially), at which point we may be able to eat them again without problems.) Food sensitivities, likewise, can often be treated when we approach them from the angle of gut health, and/or temporarily avoiding the offending food components, like FODMAPS.
With all this in mind, we should be getting the picture that so-called restrictive diets like Paleo (I say “so-called,” because diversity is really the cornerstone of Paleo!) don’t sentence us to a loss of immune tolerance. But, that doesn’t answer the question of why some of us start reacting to foods we previously could handle after we’ve switched to a healthier diet. What’s going on here?
As adults, we’ve already passed the stage where IgE-mediated food allergies tend to first begin (in infancy and early childhood). But, food allergies can develop at any point in life, including adulthood! In fact, a recent survey of almost 54,000 adults found that roughly half (47%) of all adults allergic to shellfish or nuts had developed at least one of their allergies after they turned 18. Additional research shows that when allergies do develop in adulthood, they usually begin when people are in their early 30s. Individuals with a history of getting hay fever and/or eczema have also been shown to have higher risk of developing food allergies as an adult.
Researchers are still trying to figure out what causes us to develop allergies to foods we previously handled just fine. Environmental exposures, viral infection, hormonal changes (such as during pregnancy, when hormonal shifts designed to protect the baby also impact immune function), and exposure to certain proteins while we’re in a state of weakened immunity all may play a role in allergy development. In some cases, a form of cross-reactivity called oral allergy syndrome occurs, where people start reacting to foods (especially certain fruits and vegetables) that contain proteins similar to those of an existing environmental allergy (such as latex, some plant pollens, or poison ivy). This is why, for example, people with a latex allergy might have to also avoid bananas!
When it comes to diet, though, allergies do not develop as a result of avoiding a food for too long! The early, regular exposure that plays a role in first developing immunity during infancy doesn’t have an equivalent mechanism in adults. In other words, we can’t induce a soy allergy by going a year without eating soy; we can’t induce a shellfish allergy by not eating prawns frequently enough; and we won’t go into anaphylaxis just by having spent too much time away from peanuts, and then one day eating a spoonful (or three) of peanut butter straight out of the jar! Likewise, routinely eating small amounts of a true allergen won’t help us build immune tolerance towards it. This simply isn’t how IgE-mediated allergies work in adulthood.
Intolerances and sensitivities are a different story, though! With any radical dietary shift, including Paleo or AIP, some people find themselves reacting differently to foods they’ve eaten many times before. In some cases, these changes are positive: a well-implemented Paleo diet has many elements that support gut health (such as higher fiber intake and short-chain fatty acid production, greater nutrient density, greater omega-3 intake, and the removal of food components that contribute to leaky gut, like gluten and lectins in other grains; see What Should You Eat To Heal a Leaky Gut?), creating a situation where gut barrier function is strengthened and digestion improves. Likewise, the removal of foods we previously had non-IgE immune reactions to can help us recover from the sensitivity, to the point where we may eventually be able to reintroduce the food without reacting. This is because when we avoid a triggering food, the plasma cells responsible for making antibodies against that food eventually die off (since they have finite lifespans). If we wait until these antibody-producing cells are gone, we can often get away with occasional (weekly to monthly!) consumption without experiencing a noticeable reaction. And, if we wait an even longer time until memory B cells specific to that food (which our body makes to help remember things we’ve fought before) have also died off, while also improving our immune system and healing our gut, it’s possible that our immune system won’t remember we ever had a problem with the food in question! That means freedom to enjoy that food at our leisure (assuming it’s something we actually want to keep in our diet). (We should note that memory B cells have a shorter lifespan when they remember IgG reactions than IgE reactions, which is why it’s much more likely we can reverse a food sensitivity (IgG reactions) than a true allergy (IgE reactions).)
So, if eating Paleo (or other food group-eliminating diets) can’t produce a true allergy and also has the potential to heal food sensitivities, why do some Paleo adherents report adverse reactions to foods they used to handle just fine? What’s going on here?!
Despite its tremendous healing potential, there are legitimate ways that eating Paleo (depending on how it’s implemented!) could make us more sensitive to certain foods. The most likely possibilities are:
With all this in mind, it should be clear that avoiding allergenic foods on Paleo is, itself, not going to cause a true loss of immune tolerance. So, there’s no reason to routinely eat foods like gluten grains, dairy, soy, or peanuts just to avoid developing an IgE allergy. And, when it comes to non-IgE intolerances and sensitivities, avoiding specific foods is also incredibly unlikely to cause a permanent inability to ever handle them again. At worst, we might find ourselves reacting strongly to an initial re-introduction of a food after a period of avoidance. Any negative reactions that happen outside of these scenarios are due to factors other than eliminating a specific food!
So, more than deliberately exposing ourselves to allergenic foods, what we should really be focusing on is supporting our gut health in every way possible! This is at the heart of the issue, and where most intolerances and sensitivities really originate. Even on Paleo, there are absolutely some diet and lifestyle choices that can cause gut dysbiosis and affect our ability to handle otherwise nutritious foods. Here’s how to strengthen our gut health and preserve our ability to eat our favorite foods without negative consequences!
Bottom line, we really shouldn’t worry about Paleo, AIP, or other similar diets causing long-term harm due to avoiding certain foods. When new intolerances and sensitivities emerge, they generally have less to do with the fact our diet is Paleo or AIP, and more to do with shifts in the gut microbiome, nutrient status, and other changes that are secondary to the diets themselves. So, while deciding whether to take a nibble of a wheat product once in awhile or put peanut butter on your apple slices once a week is absolutely a personal decision, we don’t need to do these things to protect our long-term health!
Berin MC & Mayer L. “Can we produce true tolerance in patients with food allergy?” J Allergy Clin Immunol. 2013 Jan;131(1):14-22. doi: 10.1016/j.jaci.2012.10.058.
Boyce JA, et al. “Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel.” J Allergy Clin Immunol. 2010 Dec;126(6 Suppl):S1-58. doi: 10.1016/j.jaci.2010.10.007.
David LA, et al. “Diet rapidly and reproducibly alters the human gut microbiome.” Nature. 2014 Jan 23;505(7484):559-63. doi: 10.1038/nature12820. Epub 2013 Dec 11.
Gocki J & Bartuzi Z. “Role of immunoglobulin G antibodies in diagnosis of food allergy.” Postepy Dermatol Alergol. 2016 Aug;33(4):253-6. doi: 10.5114/ada.2016.61600. Epub 2016 Aug 16.
Gupta R, et al. “OR077 The prevalence of nut and seafood allergies among adults in the United States.” Ann Allergy Asthma Immunol 2017;19(5):S11.
Kamar TA, et al. “Prevalence and characteristics of adult-onset food allergy.” J Allergy Clin Immunol Pract. 2015 Jan-Feb; 3(1): 114–5.e1.
Kemeny DM, et al. “Sub-class of IgG in allergic disease. I. IgG sub-class antibodies in immediate and non-immediate food allergy.” Clin Allergy. 1986 Nov;16(6):571-81.
Kumari R, et al. “Fluctuations in butyrate-producing bacteria in ulcerative colitis patients of North India.” World J Gastroenterol. 2013 Jun 14;19(22):3404-14. doi: 10.3748/wjg.v19.i22.3404.
Lam YY, et al. “Effects of dietary fat profile on gut permeability and microbiota and their relationships with metabolic changes in mice.” Obesity (Silver Spring). 2015 Jul;23(7):1429-39. doi: 10.1002/oby.21122. Epub 2015 Jun 5.
Kuo S-M. “The Interplay Between Fiber and the Intestinal Microbiome in the Inflammatory Response.” Advances in Nutrition. 2013;4(1):16-28. doi:10.3945/an.112.003046.
Leach, Jeff. “Sorry Low Carbers, Your Microbiome is Just Not That Into You.” Human Food Project. 26 June 2013. http://humanfoodproject.com/sorry-low-carbers-your-microbiome-is-just-not-that-into-you/
Szilagyi A. “Adaptation to Lactose in Lactase Non Persistent People: Effects on Intolerance and the Relationship between Dairy Food Consumption and Evalution of Diseases.” Nutrients. 2015 Aug 13;7(8):6751-79. doi: 10.3390/nu7085309.
Vickery BP, et al. “Mechanisms of immune tolerance relevant to food allergy.” J Allergy Clin Immunol. 2011 Mar;127(3):576-84; quiz 585-6. doi: 10.1016/j.jaci.2010.12.1116. Epub 2011 Jan 31.
Wawrzyniak M, et al. “Role of Regulatory Cells in Oral Tolerance.” Allergy Asthma Immunol Res. 2017 Mar;9(2):107-115. doi: 10.4168/aair.2017.9.2.107.
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There is an absolute truth that mayonnaise is essential in a Paleo diet, simply because it makes everything taste better….
Going meatless for a Paleo dinner or two? There are plenty of healthy and colorful options available in the vegetable…
Blueberries are most famous for appearing at the breakfast table. If you immediately begin thinking about sweet potato banana and…
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The trillions of microbes in our gut play incredibly important and complex roles in our health. I’ve written several articles on the gut microbiome and its connections to:
Because the health of our gut microbiome is so important, I’ve also extensively discussed why we should think twice about taking antibiotics. Thanks to more widespread appreciation of the gut microbiome, more and more patients and doctors understand the potential negative impacts of antibiotics on normal healthy bacteria. But a study published in March of this year suggests that many non-antibiotic drugs can also affect the microbiome. In this article, I’ll break down the findings of this study and discuss whether this is truly cause for concern.
The interaction of drugs and the microbiome is not a new concept. It’s been known for quite some time that microbes influence the efficacy and toxicity of drugs, and several studies had previously found that metformin (1), PPIs (2), NSAIDs (3), and atypical antipsychotics (4) can all alter the composition of the microbiota.
Antibiotics can have adverse effects on the gut microbiome, but did you know that nearly a quarter of non-antibiotic drugs can as well? Learn which of your prescriptions might be influencing your gut microbiome – for better or for worse
However, the effects of many other non-antibiotic drugs on the microbiome had never been assessed, even though many have known gastrointestinal side effects. The goal of this study, therefore, was to systematically profile interactions between drugs and individual gut microbes. It was titled “Extensive impact of non-antibiotic drugs on human gut bacteria” and published in the journal Nature.
For the study, the authors monitored the growth of 40 human gut isolates comprising 38 different bacterial species, which were grown in an anaerobic medium that largely “recapitulates the species relative abundance in human gut microbiomes.” The species were chosen based on their prevalence and abundance in the healthy human gut microbiota and their phylogenetic diversity. Most strains were commensal, or normal, gut flora, but the set also included four potential pathogens, including Clostridium difficile and the probiotic strain Lactobacillus paracasei.
They tested 1,079 pharmaceuticals that are commonly administered to humans, including:
Unsurprisingly, many of the antibacterials tested had broad-spectrum activity, meaning that they inhibited pathogenic bacteria but also inhibited normal commensal bacteria. Of the 156 antibacterials tested, 78 percent were active against at least one commensal species, and most had activity against many potentially beneficial microbes. Additionally, 47 of the 88 antifungals, antivirals, and antiparasitics had anti-commensal activity.
The most novel finding, though, was that 203 out of the 835 human-targeted non-antibiotic drugs showed activity against normal gut microbes. That’s almost a quarter (24 percent) of non-antibiotic drugs having a significant effect on the gut microbiome. Most of these drugs only inhibited the growth of a few strains, but 40 drugs affected at least 10 strains!
The effects weren’t limited by drug class, either. Almost every type of drug tested showed some activity against normal gut flora. I’ve listed the categories below, along with the specific names of drugs that affected more than 10 microbial strains:
Microbial responses varied by drug, but the abundance of key commensals Roseburia intestinalis, Eubacterium rectale, and Bacteroides vulgatus were among the most sensitive. R. intestinalis and E. rectale are known producers of the beneficial microbial metabolite butyrate, a key promoter of gut barrier integrity, while B. vulgatus is an important producer of the metabolite propionate, which stimulates the release of gut satiety peptides and has been shown to help prevent weight gain (5). The authors write:
Overall, species with higher relative abundance across healthy individuals were significantly more susceptible to human-targeted drugs. This suggests that human-targeted drugs have an even larger impact on the gut microbiome, with key species related to healthy status […] being relatively more affected. (6)
They also stressed that the doses used in the study to probe drug–microbe interactions were well within physiologically relevant concentrations and that their data are likely to underestimate the impact of human-targeted drugs on gut bacteria.
Lastly, there was a strong overlap between resistance against antibiotics and resistant against non-antibiotic drugs, suggesting that consuming non-antibiotic drugs could potentially increase the risk of acquiring antibiotic resistance.
I want to stress that there is still much we don’t understand here. For instance, is an altered gut microbiome an on-target or off-target effect of the drug? As the lead author on the study, Dr. Peer Bork, pointed out in a press release, “This shift in the composition of our gut bacteria contributes to drug side-effects, but might also be part of the drugs’ beneficial action” (7).
In other words, your prescription might only be working because it is changing your gut microbiome. For example, metformin, a drug commonly used to treat diabetes, has been shown to alter the gut microbiome, increasing abundance of the beneficial microbes Akkermansia muciniphila, Butyrivibrio, and Bifidobacterium bifidum (8). Transplanting fecal material from humans receiving metformin into germ-free mice has been shown to improve glucose intolerance, suggesting that the microbiome is responsible for the therapeutic effects (9).
All that being said, metformin seems to be the exception, not the rule—it’s clear that many of these drugs are negatively impacting microbial composition. These off-target effects on the microbiome suggest that treating one disease with a pill could potentially be causing another disease down the road. In other words, taking a proton pump inhibitor might help control your acid reflux in the short term, but it will also cause a shift in your gut microbiome that predisposes you to irritable bowel syndrome (10), gut infections (11), liver disease (12), and other conditions.
While pharmaceuticals can be a valuable tool in the management of disease, this study further supports the notion that if we can address the root cause of disease and support a healthy gut microbiome, we’re much more likely to achieve lasting, long-term health.
Now I’d like to hear from you. Did you know about the effects of non-antibiotic drugs on the gut microbiome? Start the discussion in the comments below!
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