Tag Archives: inflammation

Oyters on Grill |The Paleo Diet

Zinc! It’s the essential mineral that’s praised by many advocates involved in the Paleo community. Most people generally recognize zinc for its reputation as a potent cold and flu virus prevention solution, but its numerous benefits also extend beyond its role as an immunity-boosting mineral.

Ensuring adequate zinc intake in one’s diet is absolutely necessary for achieving long term health goals while following an ancestral eating plan. Zinc is essential for maintaining numerous physiological functions within the human body including tissue and epithelial integrity, immune system regulation, cellular growth, gut health, and inflammation suppression. The current USA government’s recommended daily allowance (RDA) for zinc averages in at approximately 10 mg. The USA RDA for zinc might be adequate for maintaining proper zinc levels for most healthy human beings that do not suffer from a zinc deficiency, but higher short-term dosages are likely needed to correct a deficiency. Physical indications of zinc deficiency include but are not limited to frequent viral infections, white spots or streaks on the fingernails, poor physical growth in childhood, hair loss, impaired vision, diarrhea, acne, dandruff, chronic dry skin, and impaired mental functioning (i.e. depression, anxiety, brain fog). It’s worth noting that all of the listed conditions can also result from the manifestation of other nutrient and mineral imbalances, and ensuring a highly varied nutrient rich ancestral diet that is rich in omega-3’s is crucial to preventing and resolving any of the aforementioned health issues.

Zinc in excess can be equally problematic as zinc deficiency. The daily upper limit threshold for zinc in healthy individuals is about 40 mg for adults over 19 and 25mg for those under 19. Excessive zinc consumption is characterized by severe headaches, nausea, vomiting, and decreased appetite. Over the long term, excessive zinc intake in the absence of copper will result in the gradual depletion of copper from the human body. For this reason it is recommended that those looking to supplement zinc in their diets should avoid zinc dietary supplements and instead opt for “au-naturel” food-based sources of zinc that are inherently proportionately balanced with copper.

Those looking to ensure optimum zinc intake in their diet must decide whether to source their zinc from animal sources or plant sources. Below are two tables demonstrating a handful of the highest ranking sources of zinc from both plants and animals. The zinc content of each source is listed in mg. Note that many of the listed zinc-rich plant foods do not adhere to the Paleo lifestyle.

Zinc Sources Table | The Paleo Diet

When examining the table above, it becomes obvious that ratio of zinc in animal-based foods is significantly higher than the ratio of zinc found in plant-based foods. Additionally, all of the animal-based sources of zinc naturally have appropriate zinc to copper ratios, so you don’t have to worry about creating a mineral imbalance while consuming these foods.

Now you might be wondering if it is still worth considering plant-based sources of zinc in your diet. From the tables above, it is immediately apparent that one would have to consume much higher quantities of zinc-containing plant foods to achieve the same proportion of zinc found in the animal foods listed above. Besides pumpkin seeds and sunflower seeds, all of the other listed plant-based zinc sources are off limits for Paleo followers. Additionally, it is worth mentioning that many of the zinc-rich plant foods such as legumes, seeds, nuts, and grains contain phytates (i.e. phytic acid). Phytates have been demonstrated to bind to zinc and other important dietary minerals such as iron and manganese. The bonding of phytates with zinc and other minerals upon digestion drastically reduces your body’s ability to absorb these key minerals, thus making you more prone to mineral deficiencies. Animal foods do not inhibit the absorption of zinc or other minerals and instead aid in absorption during digestion.

Oysters rank supreme amongst all other zinc containing food sources available for human consumption, and thus are ideal for treating individuals with zinc deficiency, and for those simply looking to incorporate zinc-rich food sources into their diets.

Oysters have long been revered for their rich taste and nutritional qualities across all parts of the globe. Preference for oyster consumption has shown up in historical documentation dating back to the ancient Greeks and Chinese. In fact, in Europe up until the 18th century oysters were considered a “luxury” food only reserved for the highest classes. Within the colonies of North America, oyster consumption was never restricted to the rich and thus most colonists and Native Americans consumed oysters regularly. The 19th century in The United States was marked by the widespread establishment of “oyster bars” that originated on the eastern seaboard and quickly became popular throughout the west. By 1881 there were nearly 379 oyster bars in Philadelphia alone! Zinc deficiency was likely not a major problem for oyster-loving 19th century Americans.

Nowadays oysters are becoming an increasingly obsolete food source. Oysters can be difficult to source fresh, especially if you are like myself and live thousands of miles inland from the nearest ocean. The best economical solution for inlanders is to purchase canned oysters from your local grocery store. A large majority of the oysters on store shelves are canned in cottonseed oil, which you will definitely want to avoid if you are sticking to a Paleo eating plan. Fortunately, Crown Prince offers a line of smoked oysters that are canned in extra-virgin olive oil. I have seen these oysters available in Sprouts, Whole Foods, and Trader Joe’s for about $2 – $3 per can. If you are not quite adjusted to the “delicious” taste of oysters yet, try topping them with a few drops of Paleo-friendly hot sauce.

References

1. Berger, Abi. “What does zinc do?.” BMJ 325.7372 (2002): 1062.
2. Hambidge, M. (2000). Human zinc deficiency. The Journal of nutrition,130(5), 1344S-1349S.
3. Lönnerdal, B. O. (2000). Dietary factors influencing zinc absorption. The Journal of nutrition, 130(5), 1378S-1383S.
4. Ma, J., & Betts, N. M. (2000). Zinc and copper intakes and their major food sources for older adults in the 1994–96 continuing survey of food intakes by individuals (CSFII). The Journal of nutrition, 130(11), 2838-2843.
5. Office of Dietary Supplements – Zinc. (n.d.). Retrieved December 28, 2015, from https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

Wheat | The Paleo Diet

Click Here to Start The Wheat Series from the Beginning!

It’s one of the most commonly used analogies in existence and it’s about a game that few want to play. A revolver is loaded with a single bullet. The hapless players take turns putting the gun to their heads and pulling the trigger. The analogy is often used to make a point about the high stakes of luck. Eventually someone gets a loaded chamber and pays the ultimate price.

There is a second side to the analogy, however that is frequently overlooked. Regardless of whether you have extremely good or bad luck, you first have to willingly pull the trigger.

We’ve known for a while that most chronic diseases such as cancer, autoimmune disease, and heart disease have a genetic component.1 – 10 Genetics are the loaded bullet that we sadly have no control over.

For celiac disease, the “bullet” is a genetic variant in HLA-DQ.11, 12 However, a large number of people with the variant never express the disease. Further, those who do develop the condition usually resolve it by removing gluten from their diet.13, 14 In other words, the bullet might be in the chamber, but often the gun is never fired.

Environmental factors ultimately pull the trigger.

In the first four parts of this series we talked about how wheat (and to a degree other gluten-containing grains such as rye and barley) is highly effective at dysregulating the immune system of our guts. In fact, it’s the only food we know of that affects all three pathways of dysregulation:

  1. Opening up the tight junctions of our gut (Part 2)
  2. Excess and chronic bacterial stress (Part 3)
  3. Harmful dietary antigens (Part 4)

In this final part, we’ll talk about how the resulting chronic inflammation leads to a pathological state that essentially “pulls the trigger” on disease. But just as importantly, we’ll discuss how there has to be a bullet in the chamber first. The genetic susceptibility has to be there.

It’s Not So Easy to Pull the Trigger

Our genetics have not changed in the last 100 years. Yet, chronic disease such as autoimmune conditions and cancer have risen dramatically. Faster than rate of population growth.

In other words, going with our analogy, the number of bullets hasn’t changed, but for some reason the trigger is getting pulled a lot more often. Which is surprising considering no one wants to pull it.

Imagine for a minute what it takes for a person to get to the point where they will voluntarily put a gun to their heads. None of us handed a revolver and told we have a five in six chance would exclaim “sure, those sound like good odds.”

From what little we understand, Russian Roulette players essentially have to build up to it, engaging in other risky behavior, and slowly desensitizing themselves. As it turns out, a lot of behavior altering substances help too.15

Likewise, our bodies have a lot of defenses to avoid ever pulling the trigger on disease, even when the bullet is there.

So, while we hopefully made the case in the previous four parts that wheat is not good for us, one piece of bread isn’t going to give you cancer. Despite all the dysregulation of our immune system caused by wheat, it still takes a lot to build up to the point of disease.16, 17

Building Up to It…

In fact, as we discussed in Part 1, all the inflammatory processes activated by wheat are both normal and necessary processes designed to deal with regular bacterial stress. Mice breed without these inflammatory responses suffer severe tissue damage and wasting disease.18, 19

Even the temporary shift in the balance between two critical immune cells – Tregs and TH17 cells – is a natural response to this inflammation. Let’s explore these two cells a little more.

In a healthy state, Tregs dominate. Their role is to suppress the immune system20 – 24 preventing it from damaging our own bodies. People unfortunate enough to have dysfunctioning Tregs suffer severe autoimmune diseas.25

TH17, on the other hand, have a murkier and less benign role. Only discovered in 2006, they solved an important puzzle for researchers. Scientists knew that T cells were involved in many conditions but none of the known T cells at the time fully explained disease development.26

With the discovery of TH17, they had their answer.26, 27

Proving to be highly inflammatory cells, TH17 effectively explained the damage in a multitude of chronic diseases16, 28 – 31 such as asthma,32 heart disease,33, 34 and most autoimmune conditions30, 35 including celiac disease,36, 37 type I diabetes,38, 39 Crohn’s disease,40, 41 rheumatoid arthritis,31, 42 and multiple sclerosis.43

A question remained, however: Why would our bodies produce such a self-destructive cell?

The reason lies in their role. It was believed that TH17 cells evolved to deal with harmful bacterial infections and effectively handling the invasion means doing some damage to our own bodies.19, 44, 45

This damage seems to be acceptable to our bodies and even part of a healthy immune response as long as one essential condition is met – the shift towards TH17 dominance is short-lived and ends. Once an infection is dealt with and the resulting inflammation quiets down, TH17 cells die off and Tregs return to dominating our immune system.24, 46

So what happens if the inflammation doesn’t end?

According to one emerging theory, the result is an out-of-control pathogenic form of the TH17 cell.10, 23, 24 In other words, if normal bacterial stress causes a little risky behavior by inciting beneficial TH17, chronic inflammation causes the buildup that leads to the pathogenic TH17 putting the gun to our heads and pulling the trigger.

Chronic Inflammation – Putting the Gun to our Heads

The diagram below shows the different responses between normal and chronic inflammation.30

Chronic Inflammation | The Paleo Diet

Kamada, N., et al., Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol, 2013. 13(5): p. 321-35.

Let’s explore this destructive shift a little more closely. Bear with me – this gets technical.

Under normal inflammation, the number of Treg cells increase alongside the TH17 cells allowing Tregs to continue controlling TH17’s destructive potential and maintain some balance.30, 47

But in chronic inflammation, a dramatic shift occurs. More and more innate immune cells such as dendritic cells and CD14+ macrophages (explained in Part 3) are activated or recruited to the digestive immune system.17, 28, 48, 49

Over time, these cells change the chemical milieu of the gut to one that is high inflammatory. Il-23 is released which both promotes the destructive form of TH17 and inhibits Tregs.27, 47, 50, 51 Newly recruited CD14+ macrophages also suppress Tregs.52

In fact, it gets worse. The chronic inflammation causes Tregs to “flip” and start behaving like TH17 contributing to the inflammation instead of preventing it.47, 52, 53

The result is that chronic inflammation breaks the Treg/ TH17 balance. Treg lose their ability to control the immune system and TH17, now uninhibited, take on a more destructive form traveling from the gut45 throughout the body pulling the trigger:30

Gut Microbiota | The Paleo Diet

Kamada, N., et al., Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol, 2013. 13(5): p. 321-35.

This is the point where you may want to remind me that this is the fifth part in a series about wheat. Where does wheat come into all of this?

Wheat, as we’ve shown in the previous parts, creates the chronic inflammation that sets off this cascade. In fact, in one study of mice, that tested many dietary antigens, wheat was the only one that could activate inflammatory TH17 cells.54

Put simply, wheat sets in motion the build-up that causes our bodies to ultimately put the gun to our heads and pull the trigger.

Why Aren’t More Guns Going Off?

The very sobering thought is that the chronic inflammation, which wheat is so effective at creating (in fact it took three parts to explain all the ways wheat can cause it,) appears to be common to everyone.17, 20, 55

So why aren’t we all sick?

This is where we need to flip things around and remember there are two parts to the Russian Roulette analogy. Wheat causes our immune system to put the gun to our heads and pull the trigger, but there still needs to be a bullet in the chamber. The genetic susceptibility has to be there.

Sure enough, a genetic susceptibility to chronic inflammation has been identified in many conditions. Often taking the form of a hyper-sensitivity to inflammation or a failure of the Treg system to suppress it.

CD14+ macrophages appear to be particularly potent in rheumatoid arthritis.56 Celiacs are hyper-sensitive to Il-15 – one of the key proteins used by wheat to produce inflammation.3 Much higher levels of inflammatory CD14+ macrophages exist in the guts of people with Irritable Bowel Disease (IBD).57 IBD sufferers also appear to be more responsive to IL-23.29 In type II diabetes, the immune cells that destroy the pancreas exist in healthy and afflicted subjects, but Treg cells appear to be less functional in diabetics.1, 2

Making a further case for the importance of genetics, people with one of these conditions are often more susceptible to the others.58-63

Still, There Are a Lot of Bullets…

The need for a “genetic bullet” in order for a disease to materialize has led many to breathe a sigh of relief. An example is the recent Washington Post article “For many, gluten isn’t the villain it gets cracked up to be.”

But the fact is that there are many chronic disease and they are all on the rise. A lot more guns are actually going off now.

Recent research is showing more and more that inappropriate chronic inflammation is at the heart of almost every “disease of civilization” including cancer,64, 65 metabolic disorders,66, 67 Alzheimer’s disease,68 most autoimmune conditions,30, 35 and heart disease where aberrant macrophages (immune cells) form the atherosclerotic plaques.69, 70

That amounts to a whole lot of genetic bullets.

While the research is still small, several of these conditions including celiac’s disease, diabetes, and     IBD are improved when wheat is removed from the diet.13, 14, 71 – 73

So feel free to do as the Washington Post article says, eat your bread, and trust your luck that the chamber is empty. But with that many potential bullets in the revolver and chronic inflammation – so effectively produced by wheat – ready to pull the trigger, I’m personally going to avoid putting the gun to my head.

References

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  16. Gonzalez-Quintial, R., et al., Systemic autoimmunity and lymphoproliferation are associated with excess IL-7 and inhibited by IL-7Ralpha blockade. PLoS One, 2011. 6(11): p. e27528.
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  37. Castellanos-Rubio, A., et al., TH17 (and TH1) signatures of intestinal biopsies of CD patients in response to gliadin. Autoimmunity, 2009. 42(1): p. 69-73.
  38. Kumar, P. and G. Subramaniyam, Molecular underpinnings of Th17 immune-regulation and their implications in autoimmune diabetes. Cytokine, 2015. 71(2): p. 366-76.
  39. Shao, S., et al., Th17 cells in type 1 diabetes. Cell Immunol, 2012. 280(1): p. 16-21.
  40. Elson, C.O., et al., Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology, 2007. 132(7): p. 2359-70.
  41. Brand, S., Crohn’s disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn’s disease. Gut, 2009. 58(8): p. 1152-67.
  42. Hirota, K., et al., Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med, 2007. 204(12): p. 2803-12.
  43. Du, C., et al., MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol, 2009. 10(12): p. 1252-9.
  44. McFall-Ngai, M., Adaptive immunity: care for the community. Nature, 2007. 445(7124): p. 153.
  45. Ivanov, II, et al., Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell, 2009. 139(3): p. 485-98.
  46. Grossman, Z., et al., Concomitant regulation of T-cell activation and homeostasis. Nat Rev Immunol, 2004. 4(5): p. 387-95.
  47. Torchinsky, M.B., et al., Innate immune recognition of infected apoptotic cells directs T(H)17 cell differentiation. Nature, 2009. 458(7234): p. 78-82.
  48. Nikulina, M., et al., Wheat gluten causes dendritic cell maturation and chemokine secretion. J Immunol, 2004. 173(3): p. 1925-33.
  49. Yamazaki, K., J.A. Murray, and H. Kita, Innate immunomodulatory effects of cereal grains through induction of IL-10. Journal of Allergy and Clinical Immunology, 2008. 121(1): p. 172-178.
  50. da Silva Martins, M. and C.A. Piccirillo, Functional stability of Foxp3+ regulatory T cells. Trends Mol Med, 2012. 18(8): p. 454-62.
  51. Lochner, M., et al., In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORgamma t+ T cells. J Exp Med, 2008. 205(6): p. 1381-93.
  52. Evans, H.G., et al., Optimal induction of T helper 17 cells in humans requires T cell receptor ligation in the context of Toll-like receptor-activated monocytes. Proc Natl Acad Sci U S A, 2007. 104(43): p. 17034-9.
  53. Voo, K.S., et al., Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci U S A, 2009. 106(12): p. 4793-8.
  54. Shi, G., et al., Cell-cell interaction with APC, not IL-23, is required for naive CD4 cells to acquire pathogenicity during Th17 lineage commitment. J Immunol, 2012. 189(3): p. 1220-7.
  55. Bernardo, D., et al., Is gliadin really safe for non-coeliac individuals? Production of interleukin 15 in biopsy culture from non-coeliac individuals challenged with gliadin peptides. Gut, 2007. 56(6): p. 889-890.
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  73. Shahbazkhani, B., et al., Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial. Nutrients, 2015. 7(6): p. 4542-4554.

Candida Overgrowth | The Paleo Diet

You’ve read about it, you’ve heard about it, and chances are you even know someone who’s dealing with Candida:  yeast overgrowth in the gut.

Candidemia, the most common form of invasive candidiasis, is one of the widespread bloodstream infections in the United States.  It’s estimated that approximately 46,000 cases of healthcare-associated invasive candidiasis occur each year in the US and overall, where candidemia rates have increased over the past 20 years.1

65+ populations exhibit Candida most where scientists suspect the prevalence of risk factors including diabetes, ICU admissions, or use of immunosuppressive therapies play a role.2

Candida albicans is a naturally occurring, usually benign yeast that grows in the gastrointestinal tract, but when it over-proliferates in the body, the symptoms can be debilitating:3

  • Recurrent yeast infections in women
  • Constipation, or diarrhea
  • Migraines
  • Weight gain
  • Skin issues like eczema and acne
  • Food sensitivities

If you’re avidly perusing the Paleosphere, you know inflammation and illness often start in the gut and are directly attribute to what we’re eating. Some go so far as to suggest that nearly everyone is suffering from candidiasis in some way, shape or form. If you have intestinal candidiasis, overgrowth of Candida in the small intestine, not only are there no risks to following a Paleo diet, its optimal for all us. Why?

Let’s look at some basic recommendations for what someone with a diagnosis of candiasis should and should not eat, courtesy of Dr. Brent A Bauer, MD of the Mayo Clinic.4

“Some complementary and alternative medicine (CAM) practitioners blame common symptoms such as fatigue, headache and poor memory on intestinal overgrowth of the fungus, like organism Candida albicans, or “yeast syndrome” and to cure the syndrome, they recommend a candida cleanse diet, which includes no sugar, white flour, yeast and cheese, based on the theory that these foods promote Candida overgrowth.”

He goes on to note that, “While there are no clinical trials that document the efficacy of a Candida cleanse diet for treating any recognized medical condition, many people note improvement in various symptoms when following this diet. If you stop eating sugar and white flour, you’ll generally wind up cutting out most processed foods, which tend to be higher in calorie content and lower in nutritive value.”

Anyone who has taken the time to properly implement a Paleo diet can vouch that after a brief transitional period, where you move to replace processed foods with fresh ones, you start to just feel better.

Because yeast thrives on sugars, it’s important to restrict sugar intake when combating a Candida infection, and remove allergenic foods and stimulants from the diet.5

Sounding familiar? Up the fresh food. Cut the sugar and refined foods. Remove allergenic foods. If that’s not a perfectly succinct description about what Paleo is all about, I don’t know what is!

If we focus upon nourishing our bodies with the rich nutrients we get from a proper Paleo approach, we boost our immune systems, balance our blood sugar levels, and ultimately, deny the yeast with food it needs to thrive, namely…refined carbs.

Ok, so is there anything else you needs to do in order to proactively fight off the excess yeast? Maura Henninger, N.D., tips published to Huffington Post6 are spot on.

  1. Starve the yeast: no sugar, which will feed the Candida. No fruit in the first two weeks of treatment, then fruit is limited to two low-glycemic choices. No milk, which has the sugar lactose that tends to promote yeast overgrowth and in some cases, because milk can contain antibiotics, can promote overgrowth. No yeast-containing foods such as alcohol, peanuts, melons are recommended. Finally, remove food sensitivities.
  1. Repopulate the gut with probiotics. Fermented foods are great for repopulating the gut with good bacteria including Kim chi, sauerkraut and coconut water.

Finally, increase the consumption of certain foods which may help to kill off the overgrowth:7

  • Monounsaturated fats to aid in fighting inflammation
  • Onions to help flush excess fluid from the body
  • Cruciferous veggies including broccoli, cauliflower and cabbage have compounds containing sulfur and nitrogen which kill Candida
  • Herbs and spices including ginger, cinnamon, cayenne pepper, garlic and cloves for their anti fungal and anti inflammatory effects

It’s clear that eating Paleo not only supports good health generally, but also helps in fighting off uncomfortable, persistent symptoms of chronic yeast overgrowth.

REFERENCES

[1] “Invasive Candidiasis Statistics.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 12 June 2015. Web. 21 Sept. 2015

[2] Cleveland AA, Harrison LH, Farley MM, Hollick R, Stein B, Chiller TM, et al. Declining Incidence of Candidemia and the Shifting Epidemiology of Candida Resistance in Two US Metropolitan Areas, 2008-2013: Results from Population-Based Surveillance. PLOS ONE. 2015

[3] Henninger, N.D. Maura. “Five Steps to Treating Candida Overgrowth, Naturally.” The Huffington Post. TheHuffingtonPost.com, n.d. Web. 21 Sept. 2015

[4] “Consumer Health.” Candida Cleanse Diet: What Does It Treat? The Mayo Clinic, n.d. Web. 21 Sept. 2015

[5] “Foods Not to Eat With Candida.” LIVESTRONG.COM. LIVESTRONG.COM, 11 Mar. 2014. Web. 21 Sept. 2015

[6] Henninger, N.D. Maura. “Five Steps to Treating Candida Overgrowth, Naturally.” The Huffington Post. TheHuffingtonPost.com, n.d. Web. 21 Sept. 2015.

[7] “Foods That Help Kill Candida.” LIVESTRONG.COM. LIVESTRONG.COM, 04 May 2015. Web. 21 Sept. 2015

New Studies on Salt: Adverse Influence Upon Immunity, Inflammation and Autoimmunity | The Paleo Diet

INTRODUCTION

The Paleo community clearly is not in complete agreement on all dietary issues. One of the more touchy topics is added dietary salt.  A number of popular (non-scientific/non-peer review) bloggers advocate the use of refined salt or various forms of sea salt added to recipes and meals.1 Highly salted meats such as bacon are wildly popular in the Paleosphere.2 Other concentrated, salty foods such as cheese, olives, canned sardines, tuna, anchovies, caviar, salted nuts, manufactured jerky, canned tomato paste, and other salted, processed foods frequently find their way into so-called Paleo diets. You will be hard pressed to find a Paleo diet cookbook anywhere that is completely free of added, salt – that is, except for one The Real Paleo Diet Cookbook (Houghton, Mifflin, Harcourt, New York, 2015).

I have written extensively on the health problems associated with added dietary salt – be it refined salt or sea salt. In the past two years startling, animal and human studies demonstrate that salt added to our diets doesn’t merely increase the risk for stroke, hypertension and heart disease,3, 4, 5, 6 but it also adversely affects immune function, promotes chronic inflammation and represents a previously unrecognized dietary factor in the pathogenesis of autoimmune diseases.7, 8, 9, 10, 11, 12

SODIUM CONSUMPTION: THE EVOLUTIONARY/ANTHROPOLOGICAL EVIDENCE

The USDA daily recommended intake of sodium is 2300 mg. However, it must be remembered that dietary sodium and dietary salt are not equivalent. 1 gram (1000 mg) of salt (NaCl) = 390 mg of sodium.  Hence 2300 mg of sodium would equal 5.9 grams of salt (NaCl).

In perhaps the most comprehensive study of hunter gatherers and non-westernized people worldwide, Denton demonstrated that their average dietary salt intake ranged from 0.6 grams to 2.9 grams of salt (NaCl) per day or 234 to 1131 mg of daily sodium.13 These numbers are derived from population wide urinary sodium excretion rates and are considerably lower than the USDA recommended value of 2300 mg sodium per day, and much lower than the wildly speculative values (3000 to 7000 mg sodium per day or 7.7 to 17.9 grams of daily salt) suggested by a non-scientific/non-peer review Paleo blogger.1

SODIUM CONSUMPTION: EVIDENCE FROM CONTEMPORARY, NON-PROCESSED FOODS

Consider Figure 1 below which demonstrates the sodium content of four contemporary Paleo foods: meat/seafoods (n=8), fruit (n=20) and vegetables (n=18). Note that meat/seafood averages 694 mg of sodium per 1000 kcal, vegetables 764 mg sodium per 1000 kcal and fruit 54 mg of sodium per 1000 kcal.

New Studies on Salt: Adverse Influence Upon Immunity, Inflammation and Autoimmunity | The Paleo Diet

Figure 1.  The Sodium Content of Contemporary Paleo Foods to Processed Foods.

Accordingly, contemporary Paleo diets averaging 55% to 66% of daily calories (range 2200 to 3000 kcal) from animal foods and the balance from plant foods would contain sodium intakes ranging from 1600 to 2200 mg.  These calculations show that unless processed foods containing added salt are consumed, it would be difficult to obtain the USDA 2300 mg recommendation for  daily sodium, and almost impossible to obtain a popular bloggers’ advice (3000 to 7000 mg sodium).1

If fruits were primarily consumed in lieu of vegetables for contemporary Paleo diets, the range of daily sodium intake would be lower still (900 to 1200 mg) which falls within the values of historically studied fully, non-westernized populations.13 With contemporary Paleo foods (fresh fruits, vegetables, meats, seafood, eggs, nuts etc.) and no added salt, you will be obtaining not only sufficient sodium intakes, but also therapeutically lower sodium intakes that are consistent with values that conditioned our species’ genome over millions of years of evolutionary wisdom.

Lowered, or no consumption of added, manufactured dietary salt will lessen your risk for hypertension, stroke and cardiovascular disease,3, 4, 5, 6 certain cancers,14, 15, 16 and now autoimmune and immune diseases, as well as multiple diseases involving chronic low level, systemic inflammation.7, 8, 9, 10, 11, 12

DIETARY SODIUM: ADVERSE EFFECTS UPON INFLAMMATION, IMMUNOLOGICAL FUNCTION AND AUTOIMMUNITY

I have now laid out the necessary foundation for the focus of this article. So, let’s get back into the topic at hand.

Unexpectedly, experimental studies in the past two years have provided powerful, new evidence that high salt diets cannot solely be related to hypertension, stroke , cardiovascular disease3, 4, 5, 6 and cancer,14, 15, 16 but also to diseases involving dysfunction of the immune system, chronic systemic inflammation and autoimmunity.7, 8, 9, 10, 11, 12

Let’s not forget that cardiovascular disease, cancer and autoimmune diseases cannot proceed without chronic, low level inflammation, or that the typical U.S diet is a high salt diet.17 Would it be surprising that the typical western diet which includes 70 % or more of its calories as salt laden processed foods17 and 10 to 12 grams of sodium per day5, 7, 17 might have any adverse effects upon the immune system and diseases of chronic inflammation?

The evolutionary discordance template18, 19 would predict that any recently introduced dietary elements found in concentrations many standard deviations above or below those which conditioned the human genome over 2 million years of evolutionary experience, might adversely impact contemporary health and well being. Indeed is the case for immunity, inflammation and autoimmunity.

ANALYSIS OF RECENT STUDIES

In April of 2013, before my recent retirement from CSU, I awoke to a flurry of emails from scientific colleagues around the world as well as from a few of my graduate students regarding two astounding papers that had just been published in the prestigious scientific journal, Nature.8, 9  These papers represented the first experimental evidence indicating that high salt diets fundamentally altered the immune system of experimental animals in a manner that promoted autoimmune disease.

Over the past decade, numerous studies (human, animal and tissue) have implicated a specific component of the immune system (Th17 or T Helper Cell 17) in a wide variety of autoimmune diseases.20, 21, 22, 23 The two papers on salt and autoimmunity published in Nature8, 9 were crucial, because for the first time empirical evidence demonstrated that high dietary intakes of salt were capable of up-regulating (increasing) Th17 cells in experimental animals and promoting autoimmunity.

OK – no big deal – these were just animal studies and until human studies were conducted, the link between dietary salt and the immune system, chronic low level inflammation and autoimmunity was tenuous.  The currency of science to demonstrate causality between diet and disease requires not just animal studies, but also tissue studies, epidemiological studies and most importantly experimental randomized controlled human trials.

Science typically moves slowly, but occasionally good ideas are rapidly pounced upon by scientists and researchers, thereby resulting in major leaps of knowledge.  Such was the case with salt and autoimmunity. Concurrent with the two animal studies on dietary salt and immune function,8, 9 came the first human study published by Zhou and colleagues, also in April of 2013.11 Their study showed that after a 7 day (short term) high salt diet (> 15  NaCl/day) compared to a lower salt (< 5 g NaCl/day), markers (CD14++ and CD16+) of pro-inflammatory immune responses increased.  CD14++ and CD16+ are molecules expressed on certain immune system cells called monocytes/macrophages. Normally, these cells produce pro-inflammatory cytokines (hormones) when bacterial infection occurs24, 25 or with autoimmune diseases.26, 27  Surprisingly, even a short term (7 day) high salt diet11 caused the human immune system to become inflamed, just as if it were being attacked by foreign pathogens24, 25 or during autoimmunity.26, 27

In the most powerful human study to date, Yi and colleagues have convincingly demonstrated that a high salt diet (12 g per day) promoted a pro-inflammatory immune response whereas a lower salt intake (6 g per day) reduced these effects and caused beneficial immune system changes. The sophistication and high scientific validity of this experiment occurred because it was conducted under metabolic ward conditions over a long (205 day) duration for a simulated spaceflight program (Mars520 Mission).7

With metabolic ward conditions, each and every meal or snack are exclusively provided to test subjects.  Consequently all nutrients (including sodium) are under strict control. During the experiment in an enclosed environment, daily salt intake was solely modified from 12 g/day to 9 g/day to 6 g/day for 50 + 10 days and then reversed back to 12 g/day for 30 days. During the high salt (12 g/day) stages of the experiment, the pro-inflammatory cytokines (localized hormones) IL-6 and IL-23 increased whereas the anti-inflammatory cytokine, IL-10 decreased. Further the high salt diet caused an expansion of white blood cells (monocytes) that occur during chronic inflammation, autoimmune diseases and cancer. On the low salt (6 g/day) diet, these deleterious immune system changes were reversed. Interestingly, during the high salt phase of this experiment, IL-17 was higher than during the low salt phase (P= 0.08). As I have mentioned earlier, numerous studies (human, animal and tissue) have implicated this specific component (Th-17) of the immune system in a wide variety of autoimmune diseases.20, 21, 22, 23

So, there you have it.  The most powerful and scientifically valid study in humans has indisputably demonstrated that a high salt diet promotes chronic inflammation and adversely affects the immune system.  Note that the high salt (12 g/day) phase of this experiment actually represents the normal (10-12 g/day) salt intake in the U.S.5, 7, 17 and that cardiovascular disease, cancer and autoimmune diseases cannot proceed without chronic inflammation.  It is not only irresponsible for certain Paleo bloggers1 to promote high salt diets, but potentially life threatening.

 

REFERENCES

[1] Kresser K. Shaking Up The Salt Myth: Healthy Salt Recommendations. May 4, 2012.

[2] Huntley T.  The Path to Culinary Bliss: Home Cured Bacon.

[3] Strazzullo P, D’Elia L, Kandala NB, Cappuccio FP. Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ. 2009 Nov 24;339:b4567. doi: 10.1136/bmj.b4567.

[4] Aaron KJ, Sanders PW. Role of dietary salt and potassium intake in cardiovascular health and disease: a review of the evidence.  Mayo Clin Proc. 2013 Sep;88(9):987-95.

[5] He FJ, MacGregor GA. A comprehensive review on salt and health and current experience of worldwide salt reduction programmes. J Hum Hypertens. 2009 Jun;23(6):363-84.

[6] Ando K, Kawarazaki H, Miura K, Matsuura H, Watanabe Y, Yoshita K, Kawamura M, Kusaka M, Kai H, Tsuchihashi T, Kawano Y. [Scientific statement] Report of the Salt Reduction Committee of the Japanese Society of Hypertension(1) Role of salt in hypertension and cardiovascular diseases. Hypertens Res. 2013 Dec;36(12):1009-19.

[7] Yi B, Titze J, Rykova M, Feuerecker M, Vassilieva G, Nichiporuk I, Schelling G, Morukov B, Choukèr A. Effects of dietary salt levels on monocytic cells and immune responses in healthy human subjects: a longitudinal study. Transl Res. 2015 Jul;166(1):103-10.

[8] Kleinewietfeld M, Manzel A, Titze J, Kvakan H, Yosef N, Linker RA, Muller DN, Hafler DA.  Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature. 2013 Apr 25;496(7446):518-22.

[9] Wu C, Yosef N, Thalhamer T, Zhu C, Xiao S, Kishi Y, Regev A, Kuchroo VK. Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature. 2013 Apr 25;496(7446):513-7.

[10] O’Shea JJ, Jones RG. Autoimmunity: Rubbing salt in the wound. Nature. 2013 Apr 25;496(7446):437-9.

[11] Zhou X1, Zhang L, Ji WJ, Yuan F, Guo ZZ, Pang B, Luo T, Liu X, Zhang WC, Jiang TM, Zhang Z, Li YM. Variation in dietary salt intake induces coordinated dynamics of monocyte subsets and monocyte-platelet aggregates in humans: implications in end organ inflammation.  PLoS One. 2013 Apr 4;8(4):e60332. doi: 10.1371/journal.pone.0060332. Print 2013.

[12] van der Meer JW1, Netea MG. A salty taste to autoimmunity. N Engl J Med. 2013 Jun 27;368(26):2520-1.

[13] Denton D.  Salt intake and high blood pressure in man. Primitive peoples, unacculturated societies: with comparisons.  In: The Hunger for Salt, An Anthropological, Physiological and Medical Analysis. Springer-Verlag, New York, 1984, pp. 556-584).

[14] D’Elia L, Rossi G, Ippolito R, Cappuccio FP, Strazzullo P. Habitual salt intake and risk of gastric cancer: a meta-analysis of prospective studies. Clin Nutr. 2012 Aug;31(4):489-98.

[15] Ge S, Feng X, Shen L, Wei Z, Zhu Q, Sun J. Association between Habitual Dietary Salt Intake and Risk of Gastric Cancer: A Systematic Review of Observational Studies.  Gastroenterol Res Pract. 2012;2012:808120. doi: 10.1155/2012/808120. Epub 2012 Oct 22.

[16] Hu J, La Vecchia C, Morrison H, Negri E, Mery L; Canadian Cancer Registries Epidemiology Research Group. Salt, processed meat and the risk of cancer. Eur J Cancer Prev. 2011 Mar;20(2):132-9.

[17] Cordain L, Eaton SB, Sebastian A, Mann N, Lindeberg S, Watkins BA, O’Keefe JH, Brand-Miller J. Origins and evolution of the Western diet: health implications for the 21st century. Am J Clin Nutr. 2005 Feb;81(2):341-54.

[18] Konner M, Eaton SB. Paleolithic nutrition: twenty-five years later. Nutr Clin Pract. 2010 Dec;25(6):594-602.

[19] Frassetto L1, Morris RC Jr, Sellmeyer DE, Todd K, Sebastian A. Diet, evolution and aging–the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet.  Eur J Nutr. 2001 Oct;40(5):200-13.

[20] Burkett PR, Meyer Zu Horste G, Kuchroo VK. Pouring fuel on the fire: Th17 cells, the environment, and autoimmunity. J Clin Invest. 2015 Jun 1;125(6):2211-9.

[21] Ryu H, Chung Y. Regulation of IL-17 in atherosclerosis and related autoimmunity. Cytokine. 2015 Apr 15. pii: S1043-4666(15)00126-X. doi: 10.1016/j.cyto.2015.03.009. [Epub ahead of print]

[22] Li D, Guo B, Wu H, Tan L, Chang C, Lu Q. Interleukin-17 in systemic lupus erythematosus: A comprehensive review.  Autoimmunity. 2015 Apr 20:1-9. [Epub ahead of print]

[23] Patel DD , Lee DM, Kolbinger F, Antoni C. Effect of IL-17A blockade with secukinumab in autoimmune diseases. Ann Rheum Dis. 2013 Apr;72 Suppl 2:ii116-23. doi: 10.1136/annrheumdis-2012-202371. Epub 2012 Dec 19.

[24] Rietschel ET, Schletter J, Weidemann B, El-Samalouti V, Mattern T, Zähringer U, Seydel U, Brade H, Flad HD, Kusumoto S, Gupta D, Dziarski R, Ulmer AJ. Lipopolysaccharide and peptidoglycan: CD14-dependent bacterial inducers of inflammation. Microb Drug Resist. 1998 Spring;4(1):37-44.

[25] Scherberich JE1, Nockher WA. CD14++ monocytes, CD14+/CD16+ subset and soluble CD14 as biological markers of inflammatory systemic diseases and monitoring immunosuppressive therapy. Clin Chem Lab Med. 1999 Mar;37(3):209-13.

[26] Chuluundorj D, Harding SA, Abernethy D, La Flamme AC. Expansion and preferential activation of the CD14(+)CD16(+) monocyte subset during multiple sclerosis.  Immunol Cell Biol. 2014 Jul;92(6):509-17.

[27] Kawanaka N1, Yamamura M, Aita T, Morita Y, Okamoto A, Kawashima M, Iwahashi M, Ueno A, Ohmoto Y, Makino H. CD14+,CD16+ blood monocytes and joint inflammation in rheumatoid arthritis. Arthritis Rheum. 2002 Oct;46(10):2578-86.

The Wheat Series Part 4: Home Invasion | The Paleo Diet

Did you miss The Wheat Series Part 1: Wheat and the Immune System? Read it HERE.
Did you miss The Wheat Series Part 2: Opening the Barrier to Poor Gut Health? Read it HERE.
Did you miss The Wheat Series Part 3: Setting Off the Bacterial Alarms – With or Without the Bacteria Read it HERE.

Nothing is scarier than someone invading your home. You’re nearly asleep when you hear the sound of something rustling downstairs. Instantly you’re awake and your internal alarm bells go off. You grab the phone. Fortunately the police are nearby and arrive almost instantly. They’ll catch the invader. You have nothing left to fear. Or do you?

The police enter the darkened house to a confusing scene. Your teenage son, sneaking home from the party you told him not to go to, has stumbled into the unknown invader. Meanwhile, your partner has entered the other side of the room carrying a baseball bat. The police can just make out three figures in the dark. Several seem armed and one may be a hostage. An officer draws her gun, but who does she point it at?

Sadly, it’s not always a happy ending. Innocent people are killed in their own homes all too often.

While a home invasion is something most of us will hopefully never experience, dealing with invaders is something our bodies have to handle thousands of times each day. And just like a thief entering your house, it would seem the job of identifying the invader – bacteria and viruses – should be a simple task. But it’s not.

The immune system – the police of our bodies – has to deal with equally dark and confusing scenarios as it tries to differentiate dangerous invaders from our own cells, beneficial microflora, and food.1-3

Fortunately, it has evolved remarkably complex systems that make it very good at determining which is which.

One food however is even better at breaking in, turning out the lights, and making the police point the gun in the wrong direction.  Wheat.

In Parts 1, 2, and 3 of this series on wheat, we talked about how wheat affects the three things that can cause the digestive immune system to dysfunction. The first was increased permeability (Part 2), the second was excess bacterial stress (Part 3). The third is the subject of this post – harmful dietary antigens.

ANTIGENS – IDENTIFYING THE INVADER

Antigens are critically important to our immune defenses. In fact, without them, most of our immune system wouldn’t be able to function. Which begs the question – what exactly are antigens?

They are just molecules. And not really any special type of molecule. Antigens exist in everything – bacteria, viruses, our food, even our own cells. As long as our immune cells can bind to it and identify it, it’s an antigen.4

Certain cells in our immune system, called antigen presenting cells (APCs), travel around our bodies “sampling” everything they encounter. They aren’t particular – they’re just as likely to check out our own cells as a foreign bacterium. They chew everything they sample into small molecules and present these antigens to the brains of our immune system – T Cells.4

T Cells are trained from birth not to respond to our own unique self-antigens which makes them remarkably good at identifying anything foreign. Together, T Cells and APCs determine when an antigen isn’t self and more importantly if it’s something to be worried about.5

Think of an antigen as an ID card. APCs and T Cells are the police hunting through the house for anyone who doesn’t belong. The more hot-headed APC likes to slam anyone it encounter up against the wall and takes their ID. It’s the T Cell who looks over their identification and decides if they belong or not. It’s the misfit buddy cop movie of our bodies.

The problem is, just like in the movies, ID cards are easy to fake. Some viruses have evolved the ability to mimic our own antigens in an attempt evade detection.6, 7

And like your daughter’s boyfriend who tends to sneak through the window at night, not everything from outside is bad (though some fathers reading this may be thinking “shoot him.”) Beneficial bacteria in our gut are foreign, but we’ve learned to live in synergy with them.2, 3, 8 Likewise, all food is technically foreign, but an immune response to we eat would lead to debilitating allergic reactions and worse.9-11
To deal with this extra level of complexity, our immune systems have developed two sophisticated “interogation” techniques – co-stimulation and oral tolerance.

CO-STIMULATION (OR THE SECOND SIGNAL)

Just identifying an antigen as foreign actually isn’t enough for a T Cell to start an immune response. The T Cell must also receive an activating signal from the APC as it presents the antigen. The APC gives this second signal when it has been exposed to a large amount of the antigen or if the body is in an inflamed state.5, 12-15

It’s the equivalent of the T Cell asking the APC “I don’t recognize this guy, should I draw my gun?” Surprisingly, the tough guy APC generally replies “What this wimp? Nah I can take him.”

ORAL TOLERANCE

This is a fancy term for not reacting to food. A special type of APC, called dendritic cells (DCs), specializes in reaching into the gut to sample food particles and microflora. Most of the time it presents the antigens with the message: “This is food. Don’t do anything.”1, 12, 14 DCs work in conjunction with a special T cell called T Regulatory (Treg) cells that respond to self-antigens instead of foreigners. But unlike other T cells, when activated, Tregs supress the immune system.12, 16-18

These two cells are the police movie equivalent of the by-the-books pencil-pushers who constantly tells the loose cannon to holster his gun. Fortunately, in our bodies, the pencil-pushers are in control most of the time.17

The image below shows the antigen identification system in action. Plasma cells, macrophages and DCs are all APCs. As you can see, in the healthy gut, Tregs dominate.19

WHEAT: THE MASTER CRIMINAL

For the rest of this post we’ll talk about how wheat is essentially a “master criminal” able to flip our antigen identification system on its head. But unlike a virus, wheat doesn’t break the system to try to evade detection. Instead it intentionally sets of the alarms and provokes the immune system to draw its guns. Tragically it’s also very good at getting immune cells to fire on the wrong target.20

THE LOCK PICKING PICKPOCKET

Part 2 of this series explained how wheat effectively opens the tight junctions of our gut allowing bacteria, large molecules and gliadin from wheat itself to enter the body.21-24

But that’s not the only way wheat breaks in.

A protein in wheat called Wheat Germ Agglutinin (WGA) is very good at binding to the cells in our digestive tract and passing right through them into our blood stream.13, 25, 26 WGA can also bind other particles. So not only can it gain entry into circulation, but it can carry antigens from the gut with it.27, 28

THE POLICE PROVOKER

Above, we discussed how the immune system doesn’t automatically respond to foreign antigens. It first needs a co-stimulation before drawing its guns. We also covered the two things that cause APCs to provide this second signal.

The first was exposure to a large quantity of antigens. By “picking the locks” to the house, wheat essentially flings open the doors allowing a huge flow of antigens from the gut into the body.

The second thing that gets APCs to provide the co-stimulation is inflammation. In Part 3 of this series, I explained how wheat tricks the body into believing it is under perpetual bacterial stress.29-33 This creates a constant inflammatory state that causes the once suppressive DCs to flip and start activating the immune system.34, 35 Other APCs follow suite.30, 32, 36-39

In other words, the once tolerant “pencil-pusher” cops of the immune system become gun happy in a way that would make Arnold Schwarzenegger cringe.13

In short, wheat ensures there’s a co-stimulation. Wheat also breaks tolerance:

WGA is able to enter the body bypassing all the mechanisms of oral tolerance.25, 28 So, the first time WGA and the food antigens bound to it are exposed to the immune system is in circulation where the response is almost always inflammatory.

Worse, in multiple studies of wheat’s effect on mice and humans, wheat reduced the levels of Treg (the immune-suppressors) in favor of a type of T Cell called Th17.29, 34, 40 We’ll explore this shift in greater detail in Part 5. All you need to know for now is Th17 is the loose cannon cop who shoots first, asks questions later.41-43

THE RED HERRING

This is the definition of an autoimmune disease. It is a condition where the immune system identifies self-antigens as foreign and attacks its own body.44 In other words, the police accidently shoot the residents.

One popular theory of how autoimmune disease comes about is the viral mimicry theory. A virus enters the body that mimics self-antigens.14 In the process of fighting the virus, the immune system ends up identifying the mimicked self-antigens as foreign.6, 7, 45

For this to happen, the body has to be in an inflamed state. That way APCs provide the co-stimulation required and they also suppress Treg cells which would otherwise prevent a reaction to self. This is why the theorists looked at viruses. Not only would they mimic self-antigens, they’d also create the necessary inflammation.7, 45

However, we’ve just seen that wheat does an equally good job of providing the co-stimulation and shutting down Treg’s. And wheat may provide the mimicry as well, so forget the virus.20, 44, 46-48

Of the over 100 autoimmune conditions identified, the trigger has been discovered for only a handful. One of those is celiac disease. In this condition, gliadin from wheat binds a protein in the body called tissue transglutaminase (tTG). The immune system reacts to tTG-gliadin antigens causing it to attack the digestive tract.39, 49, 50

Gliadin may also cross-react with neural components of the brain and contribute to conditions like multiple sclerosis, gluten ataxia, and autism.46, 47, 51 Similarly, WGA is able to bind to many different cells once inside the body.20, 26, 31 While responding to WGA, the immune system will sometimes also react to its binding tissues.20, 52

What all of this amounts to is the ending to that home invasion story none of us want to hear. Wheat and the police end up in a tense standoff and guns are drawn. Tragically your son gets mistaken for one of the invaders and gets killed in the cross-fire.

Fortunately, while wheat can dysregulate the immune system in all of us, not everyone who eats it develops an autoimmune disease. In the final part of this series we’ll talk about how genetic susceptibility is required for disease.

Read The Wheat Series Part 5: Pulling the Trigger on a Loaded Chamber HERE

 

REFERENCES

[1]du Pre, M.F. and J.N. Samsom, Adaptive T-cell responses regulating oral tolerance to protein antigen. Allergy, 2011. 66(4): p. 478-90.

[2]McFall-Ngai, M., Adaptive immunity: care for the community. Nature, 2007. 445(7124): p. 153.

[3]Ohnmacht, C., et al., Intestinal microbiota, evolution of the immune system and the bad reputation of pro-inflammatory immunity. Cell Microbiol, 2011. 13(5): p. 653-9.

[4]Murphy, K., et al., Janeway’s immunobiology. 8th ed. 2012, New York: Garland Science. xix, 868 p.

[5]Lenschow, D.J., T.L. Walunas, and J.A. Bluestone, CD28/B7 system of T cell costimulation. Annu Rev Immunol, 1996. 14: p. 233-58.

[6]Oldstone, M.B.A., Molecular mimicry and immune-mediated diseases. Faseb Journal, 1998. 12(13): p. 1255-1265.

[7]Wucherpfennig, K.W. and J.L. Strominger, MOLECULAR MIMICRY IN T-CELL-MEDIATED AUTOIMMUNITY – VIRAL PEPTIDES ACTIVATE HUMAN T-CELL CLONES SPECIFIC FOR MYELIN BASIC-PROTEIN. Cell, 1995. 80(5): p. 695-705.

[8]Smith, P.D., et al.,Intestinal macrophages and response to microbial encroachment. Mucosal Immunol, 2011. 4 (1): p. 31-42.

[9]Ahmed, T., et al., Immune response to food antigens: kinetics of food-specific antibodies in the normal population. Acta Paediatr Jpn, 1997. 39(3): p. 322-8.

[10]Seibold, F., Food-induced immune responses as origin of bowel disease? Digestion, 2005. 71(4): p. 251-260.

[11]Ganeshan, K., et al., Impairing oral tolerance promotes allergy and anaphylaxis: A new murine food allergy model. Journal of Allergy and Clinical Immunology, 2009. 123(1): p. 231-238.

[12]Williamson, E., G.M. Westrich, and J.L. Viney, Modulating dendritic cells to optimize mucosal immunization protocols. J Immunol, 1999. 163(7): p. 3668-75.

[13]de Aizpurua, H.J. and G.J. Russell-Jones, Oral vaccination. Identification of classes of proteins that provoke an immune response upon oral feeding. J Exp Med, 1988. 167(2): p. 440-51.

[14]Stepniak, D. and F. Koning, Celiac disease–sandwiched between innate and adaptive immunity. Hum Immunol, 2006. 67(6): p. 460-8.

[15]Scalapino, K.J. and D.I. Daikh, CTLA-4: a key regulatory point in the control of autoimmune disease. Immunol Rev, 2008. 223: p. 143-55.

[16]Battaglia, M., et al., IL-10-producing T regulatory type 1 cells and oral tolerance. Ann N Y Acad Sci, 2004. 1029: p. 142-53.

[17]Wing, K. and S. Sakaguchi, Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol, 2010. 11(1): p. 7-13.

[18]Veldman, C., A. Nagel, and M. Hertl, Type I regulatory T cells in autoimmunity and inflammatory diseases. International Archives of Allergy and Immunology, 2006. 140(2): p. 174-183.

[19]Macdonald, T.T. and G. Monteleone, Immunity, inflammation, and allergy in the gut. Science, 2005. 307(5717): p. 1920-5.

[20]Vojdani, A., Lectins, agglutinins, and their roles in autoimmune reactivities. Altern Ther Health Med, 2015. 21 Suppl 1: p. 46-51.

[21]Drago, S., et al., Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol, 2006. 41(4): p. 408-19.

[22]Fasano, A., Physiological, Pathological, and Therapeutic Implications of Zonulin-Mediated Intestinal Barrier Modulation Living Life on the Edge of the Wall. American Journal of Pathology, 2008. 173(5): p. 1243-1252.

[23]Fasano, A., Surprises from celiac disease. Sci Am, 2009. 301(2): p. 54-61.

[24]Lammers, K.M., et al., Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology, 2008. 135(1): p. 194-204 e3.

[25]Lavelle, E.C., et al., Mucosal immunogenicity of plant lectins in mice. Immunology, 2000. 99(1): p. 30-7.

[26]Pusztai, A., et al., Antinutritive effects of wheat-germ agglutinin and other N-acetylglucosamine-specific lectins. Br J Nutr, 1993. 70(1): p. 313-21.

[27]Ertl, B., et al., Lectin-mediated bioadhesion: preparation, stability and caco-2 binding of wheat germ agglutinin-functionalized Poly(D,L-lactic-co-glycolic acid)-microspheres. J Drug Target, 2000. 8(3): p. 173-84.

[28]Gabor, F., M. Stangl, and M. Wirth, Lectin-mediated bioadhesion: binding characteristics of plant lectins on the enterocyte-like cell lines Caco-2, HT-29 and HCT-8. J Control Release, 1998. 55(2-3): p. 131-42.

[29]Antvorskov, J.C., et al., Dietary gluten alters the balance of pro-inflammatory and anti-inflammatory cytokines in T cells of BALB/c mice. Immunology, 2013. 138(1): p. 23-33.

[30]Bernardo, D., et al., Is gliadin really safe for non-coeliac individuals? Production of interleukin 15 in biopsy culture from non-coeliac individuals challenged with gliadin peptides. Gut, 2007. 56(6): p. 889-890.

[31]Dalla Pellegrina, C., et al., Effects of wheat germ agglutinin on human gastrointestinal epithelium: insights from an experimental model of immune/epithelial cell interaction. Toxicol Appl Pharmacol, 2009. 237(2): p. 146-53.

[32]Jelinkova, L., et al., Gliadin stimulates human monocytes to production of IL-8 and TNF-alpha through a mechanism involving NF-kappaB. FEBS Lett, 2004. 571(1-3): p. 81-5.

[33]Junker, Y., et al., Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J Exp Med, 2012. 209(13): p. 2395-408.

[34]Palova-Jelinkova, L., et al., Gliadin fragments induce phenotypic and functional maturation of human dendritic cells. J Immunol, 2005. 175(10): p. 7038-45.

[35]Nikulina, M., et al., Wheat gluten causes dendritic cell maturation and chemokine secretion. J Immunol, 2004. 173(3): p. 1925-33.

[36]Harris, K.M., A. Fasano, and D.L. Mann, Monocytes differentiated with IL-15 support Th17 and Th1 responses to wheat gliadin: implications for celiac disease. Clin Immunol, 2010. 135(3): p. 430-9.

[37]Palova-Jelinkova, L., et al., Pepsin digest of wheat gliadin fraction increases production of IL-1beta via TLR4/MyD88/TRIF/MAPK/NF-kappaB signaling pathway and an NLRP3 inflammasome activation. PLoS One, 2013. 8(4): p. e62426.

[38]Thomas, K.E., et al., Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease. J Immunol, 2006. 176(4): p. 2512-21.

[39]Tuckova, L., et al., Activation of macrophages by gliadin fragments: isolation and characterization of active peptide. J Leukoc Biol, 2002. 71(4): p. 625-31.

[40]Ejsing-Duun, M., et al., Dietary gluten reduces the number of intestinal regulatory T cells in mice. Scandinavian Journal of Immunology, 2008. 67(6): p. 553-559.

[41]Langrish, C.L., et al., IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med, 2005. 201(2): p. 233-40.

[42]Evans, H.G., et al., In vivo activated monocytes from the site of inflammation in humans specifically promote Th17 responses. Proc Natl Acad Sci U S A, 2009. 106(15): p. 6232-7.

[43]Mesquita Jr, D., et al., Autoimmune diseases in the TH17 era. Braz J Med Biol Res, 2009. 42(6): p. 476-86.

[44]Sollid, L.M. and B. Jabri, Triggers and drivers of autoimmunity: lessons from coeliac disease. Nat Rev Immunol, 2013. 13(4): p. 294-302.

[45]Oldstone, M.B.A., MOLECULAR MIMICRY AND AUTOIMMUNE-DISEASE. Cell, 1987. 50(6): p. 819-820.

[46]Hadjivassiliou, M., et al., Autoantibody targeting of brain and intestinal transglutaminase in gluten ataxia. Neurology, 2006. 66(3): p. 373-7.

[47]Vojdani, A., et al., Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism. Nutr Neurosci, 2004. 7(3): p. 151-61.

[48]Alaedini, A., et al., Immune cross-reactivity in celiac disease: anti-gliadin antibodies bind to neuronal synapsin I. J Immunol, 2007. 178(10): p. 6590-5.

[49]Dieterich, W., et al., Identification of tissue transglutaminase as the autoantigen of celiac disease. Nature Medicine, 1997. 3(7): p. 797-801.

[50]Molberg, O., et al., Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nature Medicine, 1998. 4(6): p. 713-717.

[51]Vojdani, A., D. Kharrazian, and P.S. Mukherjee, The prevalence of antibodies against wheat and milk proteins in blood donors and their contribution to neuroimmune reactivities. Nutrients, 2014. 6(1): p. 15-36.

[52]Falth-Magnusson, K. and K.E. Magnusson, Elevated levels of serum antibodies to the lectin wheat germ agglutinin in celiac children lend support to the gluten-lectin theory of celiac disease. Pediatr Allergy Immunol, 1995. 6(2): p. 98-102.

The Wheat Series Part 3: Setting Off the Bacterial Alarm Bells – With or Without the Bacteria | The Paleo Diet

Did you miss The Wheat Series Part 1: Wheat and the Immune System? Read it HERE.
Did you miss The Wheat Series Part 2: Opening the Barrier to Poor Gut Health? Read it HERE.

It’s a battle that’s been waging for millions of years. Viruses, bacteria, and a variety of pathogens looking for a nice warm home have evolved more and more sophisticated techniques to evade our immune systems. In response, our immune systems developed an array of specialized cells to launch remarkably targeted attacks at these unwanted invaders.

In the face of this cellular army, pathogens discovered one of their best weapons is a microscopic form of hide-and-seek.

Viruses mimic our bodies so immune cells pass them by.1, 2 Meningitis hangs out in the nervous system where immune cells dare not go, and HIV takes up home in immune cells themselves – after, of course, dismantling a few defenses.

These are all ways of telling the immune system “keep moving, nothing to see here.”

But what would happen if instead of looking for a good hiding place, an invader actually tried to set off the immune system alarm bells? More importantly, why would an invader want to do that?

Well, imagine you’re a plant. When some hungry animal looks at you and says “lunch” you can’t really run away. Nor can you fight back. So what do you do?

You make sure that after the animal has its meal, it is sick enough to think twice about ever touching one of your brethren.

Enter wheat.

In Part One of this series on wheat, I talked about how the normally sluggish digestive immune system can become inappropriately inflamed and lead to disease. Three things can cause this: intestinal permeability (leaky gut); chronic or too high a bacterial load; and dietary antigens.

Wheat has the unique distinction of influencing all three.

The first, intestinal permeability, is promoted by wheat through the release of zonulin.3-5 We covered that in Part Two.

Let’s get to Part Three – chronic or too high a bacterial load.

Of course, you’ve probably already realized that wheat is not bacteria. True. But the same way viruses mimic our bodies, wheat has evolved ways to “mimic” bacteria. All with the purpose of setting off the immune system alarm bells – whether the bacteria is there or not.

BACTERIAL ALARM BELLS

Our bodies actually like bacteria.

At least when they stay where they belong – in the gut.6-9 In fact, in Part One, we talked about how much of our digestive immune system evolved to allow us to live with this bacteria.7, 9-11

It’s when the bacteria – especially the less friendly types such as gram negative bacteria – get into our bodies that the immune system takes action. As a result, our immune cells have developed critical tools for the sole purpose of hunting down and identifying bacteria inside the body.

Fortunately, the bad gram negative bacteria has a tell. All over its surface is something called lipopolysaccharide (LPS).12

Antigen presenting cells (APCs) hunt down bacteria using two receptors for LPS called TLR-4 and CD14.12, 13 When LPS binds TLR-4 and CD14, the immune system alarm bells go off.

The diagram below shows the basics of this sophisticated alarm system,14 but the end result is simple. The immune system spins up and inflammation ensues.

The Wheat Series Part 3: Setting Off the Bacterial Alarm Bells – With or Without the Bacteria | The Paleo Diet

WHEAT – THE GREAT BACTERIAL MIMICKER

That subtitle is actually only partially accurate. A better description might be “wheat – the boy who cried bacterial wolf.”

The problem is our bodies never learn to ignore this particular boy.

Wheat has developed a variety of sophisticated techniques for activating the LPS response. But in some cases, it does it differently from LPS, bypassing key regulatory steps such as CD14 which would otherwise prevent inflammation in places we don’t want it.6, 10

A full description of these mechanisms is beyond the scope of this article and probably your boredom limit. So, the following is only a cursory description, but with lots of journal references that will keep the geekiest of you happy.

MECHANISM 1: LET BACTERIA IN

Part Two gives an in depth description of how wheat opens up the digestive tract barrier and allows things in our gut to get into our bodies. This includes our intestinal bacteria.15

The Wheat Series Part 3: Setting Off the Bacterial Alarm Bells – With or Without the Bacteria | The Paleo Diet

In other words, wheat actually lets the wolf into the chicken coop and then cries wolf.

MECHANISM 2: HOMEBREW LPS

Wheat contains its own LPS-like molecule, sometimes called LPSw, that has similar effects but admittedly isn’t as potent as the real thing.16, 17 In one study on mice, LPSw was able to promote a bacterial immune response.17

MECHANISM 3: ATI’S

(No It’s Not a Computer Company)

At the barrier of our gut are a special type of immune cell called dendritic cells. Constantly sampling the contents of our digestive tract, tthey are the on/off switch of the immune system.18 Think of them as Paul Revere riding back to the immune system yelling “the bacteria are coming!”

Wheat contains molecules that very potently activates dendritic cells called α-Amylase/Trypsin Inhibitors (ATIs).19 They act through TLR-4 on the dendrites. And sorry to those of you who love to say you’re “gluten-free” – ATIs, which exist in many grains, are found in a different part than gluten.

ATI’s are responsible for a long known condition called Baker’s Asthma named so because it was common among people who worked with flour.20

MECHANISM 4: SKIP THE ALARM BUT GET THE RESPONSE

TLR-4 and CD14 are not strongly expressed in the gut immune system making it hard to sound the bacterial alarm in the gut.21-23 In an area of the body that’s exposed to bacteria thousands of times each day, an inflammatory response isn’t something we want.21, 22

So it should be concerning to hear that wheat has developed ways of causing the inflammatory response without bothering with TLR-4 or CD14.

The ways wheat does it gets complex. We’ll just touch on them.

First, in several studies, small amounts of gluten were able to flip the dendritic cell’s “on switch” in mice and start an inflammatory response without touching TLR-4.24, 25

Another molecule in wheat (there’s a lot) called wheat germ agglutinin (WGA) can bind and pass right through the gut barrier to interact with immune cells on the other side. WGA then promotes a highly inflammatory response26, 27 including turning dendritic cells on.

Finally, remember all those antigen presenting cells in the gut that avoid sounding the bacterial alarm bells by simply not expressing CD14? Gliadin promotes something called IL-15 which is highly effective at activating APCs that don’t express CD14.28-33

And of a variety of foods tested, gliadin was the only one able to so effectively activate these cells.33

WHAT HAPPENS WHEN YOU PREPARE FOR AN INVASION WITHOUT THE INVASION?

That’s a lot of science and frankly we only just skimmed the surface. So here’s the point – wheat is amazingly effective at activating the bacterial defence mechanisms of our immune cells.

More importantly, this response happens in everyone and not just celiac disease (though there’s evidence it’s more pronounced in celiacs).29

So what happens when our bodies mount a defense against bacteria that isn’t there? The answer to that question is the focus of the final part to this series. But the short answer is it creates a constant state of inflammation as long as we continue to eat wheat.34, 35

Recent research is now associating a state of constant inflammation with the onset of nearly all major chronic diseases36 including heart disease,37 Alzheimer’s disease,38 diabetes,39 cancer,40, 41 and overall morbidity.42

But the question remains does the inflammation that results from wheat inappropriately setting off the bacterial alarms also contribute to these conditions?

That’s a question we’ll hope to delve into in the next two parts. But fortunately, by eating a wheat-free Paleo diet, it’s a question you may never have to worry about.

Read The Wheat Series Part 4: Home Invasion HERE

 

REFERENCES

[1]Alcami, A., Viral mimicry of cytokines, chemokines and their receptors. Nat Rev Immunol, 2003. 3(1): p. 36-50.

[2]Amara, A. and J. Mercer, Viral apoptotic mimicry. Nat Rev Microbiol, 2015.

[3]Lammers, K.M., et al., Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology, 2008. 135(1): p. 194-204 e3.

[4]Drago, S., et al., Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol, 2006. 41(4): p. 408-19.

[5]Visser, J., et al., Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci, 2009. 1165: p. 195-205.

[6]Ohnmacht, C., et al., Intestinal microbiota, evolution of the immune system and the bad reputation of pro-inflammatory immunity. Cell Microbiol, 2011. 13(5): p. 653-9.

[7]McFall-Ngai, M., Adaptive immunity: care for the community. Nature, 2007. 445(7124): p. 153.

[8]Ivanov, II, et al., Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell, 2009. 139(3): p. 485-98.

[9]Cao, A.T., et al., Th17 cells upregulate polymeric Ig receptor and intestinal IgA and contribute to intestinal homeostasis. J Immunol, 2012. 189(9): p. 4666-73.

[10]Smith, P.D., et al., Intestinal macrophages and response to microbial encroachment. Mucosal Immunol, 2011. 4(1): p. 31-42.

[11]Arrieta, M.-C. and B.B. Finlay, The commensal microbiota drives immune homeostasis. Frontiers in Immunology, 2012. 3.

[12]Kawai, T., et al., Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J Immunol, 2001. 167(10): p. 5887-94.

[13]Perera, P.Y., et al., CD11b/CD18 acts in concert with CD14 and Toll-like receptor (TLR) 4 to elicit full lipopolysaccharide and taxol-inducible gene expression. J Immunol, 2001. 166(1): p. 574-81.

[14]Buer, J. and R. Balling, Mice, microbes and models of infection. Nat Rev Genet, 2003. 4(3): p. 195-205.

[15]Fasano, A., Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev, 2011. 91(1): p. 151-75.

[16]Yamazaki, K., J.A. Murray, and H. Kita, Innate immunomodulatory effects of cereal grains through induction of IL-10. Journal of Allergy and Clinical Immunology, 2008. 121(1): p. 172-178.

[17]Nishizawa, T., et al., Homeostasis as regulated by activated macrophage. I. Lipopolysaccharide (LPS) from wheat flour: isolation, purification and some biological activities. Chem Pharm Bull (Tokyo), 1992. 40(2): p. 479-83.

[18]Williamson, E., G.M. Westrich, and J.L. Viney, Modulating dendritic cells to optimize mucosal immunization protocols. J Immunol, 1999. 163(7): p. 3668-75.

[19]Junker, Y., et al., Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4. J Exp Med, 2012. 209(13): p. 2395-408.

[20]Sapone, A., et al., Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med, 2012. 10: p. 13.

[21]Kamada, N., et al., Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis. J Clin Invest, 2008. 118(6): p. 2269-80.

[22]Nagler-Anderson, C., Tolerance and immunity in the intestinal immune system. Critical Reviews in Immunology, 2000. 20(2): p. 103-120.

[23]Smythies, L.E., et al., Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J Clin Invest, 2005. 115(1): p. 66-75.

[24]Palova-Jelinkova, L., et al., Gliadin fragments induce phenotypic and functional maturation of human dendritic cells. J Immunol, 2005. 175(10): p. 7038-45.

[25]Nikulina, M., et al., Wheat gluten causes dendritic cell maturation and chemokine secretion. J Immunol, 2004. 173(3): p. 1925-33.

[26]Dalla Pellegrina, C., et al., Effects of wheat germ agglutinin on human gastrointestinal epithelium: insights from an experimental model of immune/epithelial cell interaction. Toxicol Appl Pharmacol, 2009. 237(2): p. 146-53.

[27]Gabor, F., M. Stangl, and M. Wirth, Lectin-mediated bioadhesion: binding characteristics of plant lectins on the enterocyte-like cell lines Caco-2, HT-29 and HCT-8. J Control Release, 1998. 55(2-3): p. 131-42.

[28]Harris, K.M., A. Fasano, and D.L. Mann, Monocytes differentiated with IL-15 support Th17 and Th1 responses to wheat gliadin: implications for celiac disease. Clin Immunol, 2010. 135(3): p. 430-9.

[29]Bernardo, D., et al., Is gliadin really safe for non-coeliac individuals? Production of interleukin 15 in biopsy culture from non-coeliac individuals challenged with gliadin peptides. Gut, 2007. 56(6): p. 889-890.

[30]Jelinkova, L., et al., Gliadin stimulates human monocytes to production of IL-8 and TNF-alpha through a mechanism involving NF-kappaB. FEBS Lett, 2004. 571(1-3): p. 81-5.

[31]Palova-Jelinkova, L., et al., Pepsin digest of wheat gliadin fraction increases production of IL-1beta via TLR4/MyD88/TRIF/MAPK/NF-kappaB signaling pathway and an NLRP3 inflammasome activation. PLoS One, 2013. 8(4): p. e62426.

[32]Thomas, K.E., et al., Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease. J Immunol, 2006. 176(4): p. 2512-21.

[33]Tuckova, L., et al., Activation of macrophages by gliadin fragments: isolation and characterization of active peptide. J Leukoc Biol, 2002. 71(4): p. 625-31.

[34]Nilsen, E.M., et al., Gluten activation of peripheral blood T cells induces a Th0-like cytokine pattern in both coeliac patients and controls. Clin Exp Immunol, 1996. 103(2): p. 295-303.

[35]Antvorskov, J.C., et al., Dietary gluten alters the balance of pro-inflammatory and anti-inflammatory cytokines in T cells of BALB/c mice. Immunology, 2013. 138(1): p. 23-33.

[36]Hotamisligil, G.S., Inflammation and metabolic disorders. Nature, 2006. 444(7121): p. 860-867.

[37]Libby, P., P.M. Ridker, and A. Maseri, Inflammation and atherosclerosis. Circulation, 2002. 105(9): p. 1135-1143.

[38]Akiyama, H., et al., Inflammation and Alzheimer’s disease. Neurobiology of Aging, 2000. 21(3): p. 383-421.

[39]Xu, H.Y., et al., Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. Journal of Clinical Investigation, 2003. 112(12): p. 1821-1830.

[40]Grivennikov, S.I., F.R. Greten, and M. Karin, Immunity, Inflammation, and Cancer. Cell, 2010. 140(6): p. 883-899.

[41]Coussens, L.M. and Z. Werb, Inflammation and cancer. Nature, 2002. 420(6917): p. 860-867.

[42]Krabbe, K.S., M. Pedersen, and H. Bruunsgaard, Inflammatory mediators in the elderly. Exp Gerontol, 2004. 39(5): p. 687-99.

Ghee | Paleo Diet

Released from The Insider Vault: What’s the Skinny on Ghee?

I’m often asked is ghee Paleo? If you are not familiar with ghee, it comes from the Sanskrit word ghrita, meaning bright, and is clarified butter fat in which most of the water has been boiled off and the nonfat solids removed by continued heating, filtration, or decanting the remaining oil mixture.1 Traditional societies in India and elsewhere have produced and consumed ghee since at least 1500 BC.1

HOW IS IT MANUFACTURED?1

  1. Milk butter or desi method
  2. Direct cream method
  3. Cream butter method
  4. Pre-stratification method

All four commercial procedures to produce ghee rely upon heating at temperatures from 105° to 118° C to remove the water.1

Ghee typically contains milk fat (99 to 95%), water (< 0.5%) and protein (0.1%). The butter fat remaining in ghee after boiling and removal of nonfat solids contains saturated fatty acids (53.9 to 66.8%), polyunsaturated and monounsaturated fatty acids (22.8 to 38%), free fatty acids bound to albumin (1-3%), and cholesterol (0.15 to 0.30%).1, 2

In 1987, Jacobson first pointed out that ghee contained high concentrations (12.3%) of oxidized cholesterol, otherwise known as oxysterols.3 He suggested that consumption of ghee, with its high levels of oxidized cholesterol, by Indian immigrant population living in the UK likely represented an important dietary risk factor for atherosclerosis and heart disease.3 In subsequent years, it has been conclusively demonstrated in human, animal and epidemiological studies that dietary intake of oxidized cholesterol accelerates the rate of atherosclerosis or the hardening of the arteries, as well as increasing the size of the arterial plaque.4, 5, 6 Hence because of their atherogenic, cytotoxic and pro-inflammatory effects, oxidized cholesterol food products are almost universally recommended to be reduced or minimized in our diets.7, 8, 9

The final aspect of the ghee story that requires further scrutiny is the high concentration (12.3%) of oxidized cholesterol that Jacobson initially reported in
1987.3 This value has been questioned because of the analytical procedures that were used to measure the oxidized cholesterol.9 More recent studies suggest this
high value may have been incorrect.9, 10, 11

Fresh butter and cream samples contain barely detectable concentrations of oxidized cholesterol, whereas ghee manufactured at temperatures below 120°C contained 1.3% oxidized cholesterol.10, 11

Whether or not regular consumption of oxidized cholesterol at this lower concentration can still induce atherosclerosis in humans is currently unknown. However, part of the problem with ghee is that it is frequently used to fry food or is re-used many times in cooking foods. Both of these procedures are known to increase oxidized cholesterol to levels known to cause atherosclerosis in animal models.4 Foods fried in ghee may contain 7.1% oxidized cholesterol, whereas intermittently heated ghee contains 8.1 to 9.2% oxidized cholesterol.10

My advice is to skip ghee altogether and replace it with virgin olive oil for Paleo cooking and in salads.

 

References

1. Sserunjogi ML, Abrahamsen RK, Narvhus J. A review paper: Current knowledge of ghee and related products. Int Dairy J. 1998;8:677–88.

2. Sarojini JK, Ubhayasekera SJ, Kochhar SP, Dutta PC. Lipids and lipid oxidation with emphasis on cholesterol oxides in some Indian sweets available in London. Int J Food Sci Nutr. 2006 Nov-Dec;57(7-8):451-8.

3. Jacobson MS. Cholesterol oxides in Indian ghee: possible cause of unexplained high risk of atherosclerosis in Indian immigrant populations. Lancet. 1987 Sep 19;2(8560):656-8.

4. Soto-Rodríguez I, Campillo-Velázquez PJ, Alexander-Aguilera A, Rodríguez-Estrada MT, Lercker G, Garcia HS. Biochemical and histopathological effects of dietary oxidized cholesterol in rats. J Appl Toxicol. 2009 Nov;29(8):715-23

5. Staprans I, Pan XM, Rapp JH, Feingold KR. The role of dietary oxidized cholesterol and oxidized fatty acids in the development of atherosclerosis. Mol Nutr Food Res. 2005 Nov;49(11):1075-82.

6. Staprans I, Pan XM, Rapp JH, Moser AH, Feingold KR. Ezetimibe inhibits the incorporation of dietary oxidized cholesterol into lipoproteins. J Lipid Res. 2006 Nov;47(11):2575-80.

7. Otaegui-Arrazola A, Menéndez-Carreño M, Ansorena D, Astiasarán I.Oxysterols: A world to explore.Food Chem Toxicol. 2010 Dec;48(12):3289-303.

8. Hur SJ, Park, GB, Joo ST. Formation of cholesterol oxidation products (COPs) in animal products. Food Control 2007;18:939-947.

9. Sieber R. Oxidised cholesterol in milk and dairy products. Int Dairy J 2005;15:191-206.

10. Kumar, N. and Singhal, O. P. (1992), Effect of processing conditions on the oxidation of cholesterol in ghee. J. Sci. Food Agric., 58: 267–273.

11. Kumar MV, Sambaiah K, Lokesh BR. Effect of dietary ghee–the anhydrous milk fat, on blood and liver lipids in rats. J Nutr Biochem. 1999 Feb;10(2):96-104.

The Wheat Series Part 1: Wheat and the Immune System | The Paleo Diet

With a rapidly growing body of nutrition science covering everything from dietary proteins, to microflora composition, to caloric expenditure and cell bioenergetics, it’s surprising that still one of the hardest arguments to counter remains “I’ve always eaten it and I’m fine.” It’s a point my 97 year old grandmother likes to make every time she asks me about my research.

Let me tell you, arguing with a 97 year old about health is not easy.

The epidemiological version of the “I’m fine” argument is an assertion we hear a lot: while evidence exists that people with celiac disease cannot eat wheat, there is no proof that consuming a gluten-free diet will benefit the rest of the population.1, 2

Celiac sufferers can’t eat wheat. We know that. But it certainly appears that most people can have their bagel, get on with their days, and be just fine. Even live to see a century.

The “I’m fine” argument certainly appears to hold up on the surface. The underlying danger, however, is that the term “fine” is so remarkably subjective.

Take the case of tennis player Novak Djokovic. He went gluten-free in 2011 and then proceeded to have the most successful season in tennis history reaching number one in the process. He was certainly fine when he was eating wheat. He was just better without it.

So let’s take the subjectivity out of fine. Since we define a Paleo Diet as eating what we were designed to eat, perhaps a Paleo way of defining “fine” is functioning the way we were designed to function.

Looked at this way, there is in fact a great deal of research showing the various ways in which wheat causes our bodies to function abnormally. A select unfortunate few, such as celiacs and diabetics, may take the brunt of it, but none of us function normally eating wheat. None of us are fine.

This article is the first part in our wheat series summarizing current research on wheat and the immune system. The next few pieces will detail how wheat causes our bodies to stop functioning the way they were designed to function and can, ultimately, lead to disease. But to understand the damage, let’s start by examining what our digestive immune system looks like when it’s functioning just fine.

The Fine-Functioning Gut

Our digestive immune system is one of the most complex and robust systems in our bodies. Some 50×109 immune cells reside in the gut-associated lymphoid tissue (GALT) which makes up the bulk of our immune cells.3

But why are there so many immune cells in the gut? Because, as the image below shows, the gut is an area of constant stress. The digestive tract is continually bombarded by bacteria, food particles, and pathogens.4,5

The Wheat Series Part 1: I’ve Always Eaten It and I’m Fine… Right? | The Paleo Diet

MacDonald, T.T. and G. Monteleone, Immunity, inflammation, and allergy in the gut. Science, 2005. 307(5717): p. 1920-1925.

This image is actually a highly simplified version of what goes on in the GALT. The reality is a complex mix of T Cells, monocytes, cytokines, chemokines, interleukins, adhesion molecules, and intricate processes that would have you running for a book on brain surgery to give yourself some light reading.

Don’t worry, we’re not going to cover all that.

We’re just going to focus on a few key concepts that will hopefully prove to be fascinating. But to do that we need to introduce just a few of the important players in the gut:

First is a row of tightly packed cells that keep the contents of the digestive tract from getting into the body. It is our first line of defense and normally very effective at keeping things out.6,7Leaky gut” is just a term we use for when this barrier breaks down.

Next in our line of defense are antigen presenting cells (APCs.) They are the macrophages, dendritic, and plasma cells in the image above. These cells “sample” all the food particles, bacteria, and pathogens in the gut and present them to the immune system.

The final players you need to know for this article are T Cells. They are the generals of the immune system. Antigens are presented to the T Cells and then they decide how to respond.

It’s All About Bacteria

Generally when we think about what our immune system deals with, we think about viruses and pathogens and all those nasty things on airplanes and in our kid’s kindergarten classes.

But the truth is, dealing with a pathogen is a rare thing for our digestive immune system. Most of its energy is spent managing our microflora – those beneficial bacteria we pop probiotics and eat yoghurt to encourage. We need them for our health. We just also need them to stay in our gut because they aren’t so beneficial inside our bodies.8,9,10,11

If you’re wondering how big a role these bacteria play, remember there are more cells in our microflora than cells in our own bodies.

They are so important in fact that several researchers proposed that our digestive immune system evolved not because of pathogens but to allow us to live in harmony with our microflora.5,9,11,12

This is a critical distinction!

If a pathogen or even the normally healthy bacteria in our gut gets into our blood, our bodies mount an immediate and strong inflammatory response.13,14 This inflammation is what causes the aches, fever, and chill we associated with being sick.

The response to a bacterial infection in circulation, though damaging, is necessary and keeps us alive. Fortunately, bacteria rarely gets into our blood.

In the gut, on the other hand, the immune system is exposed to bacteria thousands of times each day. An inflammatory response every time would be deadly.5, 15 There’s even a name for this out of control inflammation – sepsis.16

As a result, the digestive immune system takes a very different tact with our beneficial bacteria. It becomes anergic – meaning it actually blocks inflammation.17,18 Special immune cells in the gut called T regulatory (Treg) cells and a unique type of APC cell actively shut down the inflammatory response and then quietly take out the invading bacteria one-by-one.3,15

The Wheat Series Part 1: I’ve Always Eaten It and I’m Fine… Right? | The Paleo Diet

Zeng, H. and H. Chi, Metabolic control of regulatory T cell development and function. Trends in Immunology. 36(1): p. 3-12.

We All Get Inflamed Sometimes

As effective as this system is, bacteria still periodically get the upper hand and an inflammatory response in the gut becomes a necessary evil.

Several things happen. First, gut APCs lose their anergy.20, 21  Second, naturally inflammatory immune cells from the blood are recruited to the gut.5,22 Finally, the Treg cells that are so effective at keeping inflammation down give way to a unique T cell called Th17 cells.

Th17 cells are powerful immune cells believed to have a single purpose – control bacterial infections.8,11,23 They are highly effective at killing bacteria, but they can also be very damaging to our own bodies. It’s the price we pay to manage our microflora, but not one we want to pay often.9,10

Ultimately, the gut remains fine as long as the inflammation ramps up quickly, kills the infection, and then backs down.

The following diagram shows this shift in Treg/Th17 balance during infection:

The Wheat Series Part 1: I’ve Always Eaten It and I’m Fine… Right? | The Paleo Diet

Arrieta, M.-C. and B.B. Finlay, The commensal microbiota drives immune homeostasis. Frontiers in Immunology, 2012. 3

When It Stops Being Fine

Problems arise when the bacterial infestation becomes overwhelming or when the inflammation simply doesn’t go away.5,8

As the inflammation continues, the imbalance between anti-inflammatory Treg cells and inflammatory Th17 cells builds on itself until finally the Tregs can’t control the Th17 cells anymore.24,25,26,27

The Wheat Series Part 1: I’ve Always Eaten It and I’m Fine… Right? | The Paleo Diet

Ohnmacht, C., et al., Intestinal microbiota, evolution of the immune system and the bad reputation of pro-inflammatory immunity. Cell Microbiol, 2011. 13(5): p. 653-9.

No longer protective, Th17 cells can then enter other parts of the bodies and contribute to a variety of chronic diseases.28,29 such as asthma,30 heart disease,31, 32 and most autoimmune conditions28,33 including celiac disease,34,35 type I diabetes,36,37 Crohn’s disease,38,39 rheumatoid arthritis,29,40 and multiple sclerosis.41

The Three Pathways to a Not Fine Gut

This highly pathogenic Th17 imbalance is a result of an abnormally functioning digestive immune system. Three things are known to cause it:

  1. Increased intestinal permeability (leaky gut)
  2. Chronic or two high a bacterial load
  3. Food particles that can hurt immune function

So now that you’ve plowed through all of that only-interesting-to-people-like-me immune function information, here’s the really fascinating point:

Wheat is the only food we’re aware of that causes all three.

In the remaining articles in this series, I will share with you the surprisingly large number of ways in which wheat breaks down the normal intestinal immune system and leads to damaging Th17 development.42, 43

More importantly, I will show you that it happens in everyone. In other words, a normally healthy gut exposed to wheat isn’t fine in anyone. Stay tuned!

Read The Wheat Series Part 2: Opening the Barrier to Poor Gut Health HERE

Trevor Connor

Trevor Connor | The Paleo DietTrevor Connor is Dr. Cordain’s last mentored graduate student and will complete his M.S. in HES and Nutrition from the Colorado State University this year and later enter the Ph.D. program. Connor was the Principle Investigator in a large case study, approximately 100 subjects, in which he and Dr. Cordain examined autoimmune patients following The Paleo Diet or Paleo-like diets.

 

REFERENCES

[1]Ferch, C.C. and W.D. Chey, Irritable Bowel Syndrome and Gluten Sensitivity Without Celiac Disease: Separating the Wheat From the Chaff. Gastroenterology, 2012. 142(3): p. 664-666.

[2]Gaesser, G.A. and S.S. Angadi, Gluten-Free Diet: Imprudent Dietary Advice for the General Population? Journal of the Academy of Nutrition and Dietetics, 2012. 112(9): p. 1330-1333.

[3]du Pre, M.F. and J.N. Samsom, Adaptive T-cell responses regulating oral tolerance to protein antigen. Allergy, 2011. 66(4): p. 478-90.
[4]MacDonald, T.T. and G. Monteleone, Immunity, inflammation, and allergy in the gut. Science, 2005. 307(5717): p. 1920-1925.

[5]Smith, P.D., et al., Intestinal macrophages and response to microbial encroachment. Mucosal Immunol, 2011. 4(1): p. 31-42.

[6]Visser, J., et al., Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci, 2009. 1165: p. 195-205.

[7]Yu, Q.H. and Q. Yang, Diversity of tight junctions (TJs) between gastrointestinal epithelial cells and their function in maintaining the mucosal barrier. Cell Biol Int, 2009. 33(1): p. 78-82.

[8]Ohnmacht, C., et al., Intestinal microbiota, evolution of the immune system and the bad reputation of pro-inflammatory immunity. Cell Microbiol, 2011. 13(5): p. 653-9.

[9]McFall-Ngai, M., Adaptive immunity: care for the community. Nature, 2007. 445(7124): p. 153.

[10]Ivanov, II, et al., Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell, 2009. 139(3): p. 485-98.

[11]Cao, A.T., et al., Th17 cells upregulate polymeric Ig receptor and intestinal IgA and contribute to intestinal homeostasis. J Immunol, 2012. 189(9): p. 4666-73.

[12]Arrieta, M.-C. and B.B. Finlay, The commensal microbiota drives immune homeostasis. Frontiers in Immunology, 2012. 3.

[13]Koj, A., Initiation of acute phase response and synthesis of cytokines. Biochim Biophys Acta, 1996. 1317(2): p. 84-94.

[14]Ohl, M.E. and S.I. Miller, Salmonella: a model for bacterial pathogenesis. Annu Rev Med, 2001. 52: p. 259-74.

[15]Smythies, L.E., et al., Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J Clin Invest, 2005. 115(1): p. 66-75.

[16]Bone, R.C., et al., DEfinitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. the accp/sccm consensus conference committee. american college of chest physicians/society of critical care medicine. Chest, 1992. 101(6): p. 1644-1655.

[17]Kamada, N., et al., Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis. J Clin Invest, 2008. 118(6): p. 2269-80.

[18]Nagler-Anderson, C., Tolerance and immunity in the intestinal immune system. Critical Reviews in Immunology, 2000. 20(2): p. 103-120.

[19]Zeng, H. and H. Chi, Metabolic control of regulatory T cell development and function. Trends in Immunology. 36(1): p. 3-12.

[20]Williamson, E., G.M. Westrich, and J.L. Viney, Modulating dendritic cells to optimize mucosal immunization protocols. J Immunol, 1999. 163(7): p. 3668-75.

[21]Burcelin, R., L. Garidou, and C. Pomie, Immuno-microbiota cross and talk: the new paradigm of metabolic diseases. Semin Immunol, 2012. 24(1): p. 67-74.

[22]Yamazaki, K., J.A. Murray, and H. Kita, Innate immunomodulatory effects of cereal grains through induction of IL-10. J Allergy Clin Immunol, 2008. 121(1): p. 172-178 e3.

[23]Reynolds, J.M., et al., Cutting edge: regulation of intestinal inflammation and barrier function by IL-17C. J Immunol, 2012. 189(9): p. 4226-30.

[24]Zhou, X., et al., Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat Immunol, 2009. 10(9): p. 1000-7.

[25]Scalapino, K.J. and D.I. Daikh, CTLA-4: a key regulatory point in the control of autoimmune disease. Immunol Rev, 2008. 223: p. 143-55.

[26]Ejsing-Duun, M., et al., Dietary gluten reduces the number of intestinal regulatory T cells in mice. Scand J Immunol, 2008. 67(6): p. 553-9.

[27]Lochner, M., et al., In vivo equilibrium of proinflammatory IL-17+ and regulatory IL-10+ Foxp3+ RORgamma t+ T cells. J Exp Med, 2008. 205(6): p. 1381-93.

[28]Kamada, N., et al., Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol, 2013. 13(5): p. 321-35.

[29]Tesmer, L.A., et al., Th17 cells in human disease. Immunological Reviews, 2008. 223: p. 87-113.

[30]Cosmi, L., et al., Th17 cells: new players in asthma pathogenesis. Allergy, 2011. 66(8): p. 989-98.

[31]Taleb, S., A. Tedgui, and Z. Mallat, IL-17 and Th17 cells in atherosclerosis: subtle and contextual roles. Arterioscler Thromb Vasc Biol, 2015. 35(2): p. 258-64.

[32]van Bruggen, N. and W. Ouyang, Th17 cells at the crossroads of autoimmunity, inflammation, and atherosclerosis. Immunity, 2014. 40(1): p. 10-2.

[33]Singh, R.P., et al., Th17 cells in inflammation and autoimmunity. Autoimmun Rev, 2014. 13(12): p. 1174-81.

[34]Monteleone, I., et al., Characterization of IL-17A-producing cells in celiac disease mucosa. J Immunol, 2010. 184(4): p. 2211-8.

[35]Castellanos-Rubio, A., et al., TH17 (and TH1) signatures of intestinal biopsies of CD patients in response to gliadin. Autoimmunity, 2009. 42(1): p. 69-73.

[36]Kumar, P. and G. Subramaniyam, Molecular underpinnings of Th17 immune-regulation and their implications in autoimmune diabetes. Cytokine, 2015. 71(2): p. 366-76.

[37]Shao, S., et al., Th17 cells in type 1 diabetes. Cell Immunol, 2012. 280(1): p. 16-21.

[38]Elson, C.O., et al., Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology, 2007. 132(7): p. 2359-70.

[39]Brand, S., Crohn’s disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn’s disease. Gut, 2009. 58(8): p. 1152-67.

[40]Hirota, K., et al., Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med, 2007. 204(12): p. 2803-12.

[41]Du, C., et al., MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol, 2009. 10(12): p. 1252-9.

[42]Antvorskov, J.C., et al., Dietary gluten alters the balance of pro-inflammatory and anti-inflammatory cytokines in T cells of BALB/c mice. Immunology, 2013. 138(1): p. 23-33.

[43]Antvorskov, J.C., et al., Impact of dietary gluten on regulatory T cells and Th17 cells in BALB/c mice. PLoS One, 2012. 7(3): p. e33315.

Fight Inflammation with a Paleo Diet

Most athletes are well aware of a fun little word called “inflammation”.1 Tough workouts are a common cause of inflammation. Acute inflammation (the only kind most people are aware of) is actually beneficial.2, 3 But – and this is a big BUT – chronic inflammation is a killer. Literally.4, 5, 6 The difference here is important, and very misunderstood. One of the biggest health benefits of consuming a Paleo diet comes from its anti-inflammatory nature.7, 8, 9 By fixing the Standard American Diet (SAD) ratio of high omega-6 to low omega-3, nearly everyone sees improvements.10, 11 But before we proceed further, let’s specify and define acute inflammation and chronic inflammation.

Fight Inflammation with a Paleo Diet

Imai, Yumi, Anca D. Dobrian, Margaret A. Morris, and Jerry L. Nadler. “Islet Inflammation: A Unifying Target for Diabetes Treatment?” Science Direct. Trends in Endocrinology & Metabolism, July 2013. Web. 25 Mar. 2015.

Fight Inflammation with a Paleo Diet

Heneka, Michael T., Markus P. Kummer, and Eicke Latz. “Innate Immune Activation in Neurodegenerative Disease.” Immunology Reviews. Nature, 25 June 2014. Web. 25 Mar. 2015.

Acute inflammation is what occurs when you get a bruise, cut, experience stress, or go through a hard workout.12 I used to practice Brazilian Jiu Jitsu and CrossFit on a near-daily basis, and I became very familiar with inflammation! However, this is the good kind of inflammation, remember. Without acute inflammation, you would never heal. Think about that for a minute. Chronic inflammation, by contrast, is problematic for two reasons. One, it is much less noticeable. You likely won’t have a bruise, cut, or any obvious symptoms. And two, it is the cause behind most serious diseases – whether it be cancer, heart disease or other conditions.13, 14, 15

With regard to diet, inflammation also plays a bigger role than most are aware of. Take acne, for example. This is an inflammatory condition. Some have even surmised that inflammation plays a role in acne at a subclinical level.16 This is one of the many reasons why dairy should be avoided when consuming a Paleo Diet. Perhaps surprisingly to some, coconut oil has been shown to have components which help protect against acne.17 The lauric acid found in coconut oil has anti-bacterial and anti-inflammatory properties, and would therefore also be beneficial after a tough workout.18 Win-win.

Vegetables are another key component of an anti-inflammatory diet, and unsurprisingly, a healthy Paleo diet is largely comprised of vegetables!19, 20 So what should athletes be eating? Coconut oil, protein and vegetables! Of course you’ll also want some anti-inflammatory fats, like the omega-3 fatty acids found in wild-caught seafood.21 From strictly a scientific perspective, it is quite clear athletes should stick to a diet based upon these foods to provide you with the best results.

Fight Inflammation with a Paleo Diet

Dantzer, Robert et al. “From Inflammation to Sickness and Depression: When the Immune System Subjugates the Brain.” Nature reviews. Neuroscience 9.1 (2008): 46–56. PMC. Web. 25 Mar. 2015.

Another aspect of inflammation which many are unaware of is that it can occur (and often does occur) in your brain!22 If the brain’s barrier is opened, your glial cells will likely be activated.23 These are the cells that deal with immunity. Once activated, an inflammatory response in your brain occurs.24 This is not good. To add to the fun, your brain now has trouble communicating with your gut, creating more issues, specifically serotonin biosynthesis problems.25 And, the delicate HPA (hypothalamus, pituitary, adrenal) axis will now likely be off-balance, as well.26

So, what is the best way to avoid inflammation, of all kinds (except beneficial, acute inflammation)? Quite simply: eat a Paleo diet. By avoiding gluten (a huge instigator of inflammation throughout the body and brain) you will be doing yourself a huge favor.27, 28 And when we replace problematic proteins like gluten, with nutrient-dense foods rich in protein, antioxidants and anti-inflammatory compounds, we procure better health for ourselves.29 Your mom was right: eat your vegetables for better health and less inflammation.30 Stay the course with a Paleo Diet and optimal health sans inflammation is within reach.

 

REFERENCES

[1] Pinto A, Di raimondo D, Tuttolomondo A, Buttà C, Milio G, Licata G. Effects of physical exercise on inflammatory markers of atherosclerosis. Curr Pharm Des. 2012;18(28):4326-49.

[2] Pedersen BK. The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control. Essays Biochem. 2006;42:105-17.

[3] You T, Arsenis NC, Disanzo BL, Lamonte MJ. Effects of exercise training on chronic inflammation in obesity : current evidence and potential mechanisms. Sports Med. 2013;43(4):243-56.

[4] Osiecki H. The role of chronic inflammation in cardiovascular disease and its regulation by nutrients. Altern Med Rev. 2004;9(1):32-53.

[5] Peev V, Nayer A, Contreras G. Dyslipidemia, malnutrition, inflammation, cardiovascular disease and mortality in chronic kidney disease. Curr Opin Lipidol. 2014;25(1):54-60.

[6] Kelly E, Owen CA, Pinto-plata V, Celli BR. The role of systemic inflammatory biomarkers to predict mortality in chronic obstructive pulmonary disease. Expert Rev Respir Med. 2013;7(1):57-64.

[7] De punder K, Pruimboom L. The dietary intake of wheat and other cereal grains and their role in inflammation. Nutrients. 2013;5(3):771-87.

[8] Soares FL, De oliveira matoso R, Teixeira LG, et al. Gluten-free diet reduces adiposity, inflammation and insulin resistance associated with the induction of PPAR-alpha and PPAR-gamma expression. J Nutr Biochem. 2013;24(6):1105-11.

[9] Nowlin SY, Hammer MJ, D’eramo melkus G. Diet, inflammation, and glycemic control in type 2 diabetes: an integrative review of the literature. J Nutr Metab. 2012;2012:542698.

[10] Kowalski LM, Bujko J. [Evaluation of biological and clinical potential of paleolithic diet]. Rocz Panstw Zakl Hig. 2012;63(1):9-15.

[11] Jönsson T, Granfeldt Y, Lindeberg S, Hallberg AC. Subjective satiety and other experiences of a Paleolithic diet compared to a diabetes diet in patients with type 2 diabetes. Nutr J. 2013;12:105.

[12] Ryan GB, Majno G. Acute inflammation. A review. Am J Pathol. 1977;86(1):183-276.

[13] Holmes C, Cunningham C, Zotova E, et al. Systemic inflammation and disease progression in Alzheimer disease. Neurology. 2009;73(10):768-74.

[14] Mcmillan DC, Elahi MM, Sattar N, Angerson WJ, Johnstone J, Mcardle CS. Measurement of the systemic inflammatory response predicts cancer-specific and non-cancer survival in patients with cancer. Nutr Cancer. 2001;41(1-2):64-9.

[15] Gomes de lima KV, Maio R. Nutritional status, systemic inflammation and prognosis of patients with gastrointestinal cancer. Nutr Hosp. 2012;27(3):707-14.

[16] Tanghetti EA. The role of inflammation in the pathology of acne. J Clin Aesthet Dermatol. 2013;6(9):27-35.

[17] Huang WC, Tsai TH, Chuang LT, Li YY, Zouboulis CC, Tsai PJ. Anti-bacterial and anti-inflammatory properties of capric acid against Propionibacterium acnes: a comparative study with lauric acid. J Dermatol Sci. 2014;73(3):232-40.

[18] Huang WC, Tsai TH, Chuang LT, Li YY, Zouboulis CC, Tsai PJ. Anti-bacterial and anti-inflammatory properties of capric acid against Propionibacterium acnes: a comparative study with lauric acid. J Dermatol Sci. 2014;73(3):232-40.

[19] Watzl B. Anti-inflammatory effects of plant-based foods and of their constituents. Int J Vitam Nutr Res. 2008;78(6):293-8.

[20] Galland L. Diet and inflammation. Nutr Clin Pract. 2010;25(6):634-40.

[21] Wall R, Ross RP, Fitzgerald GF, Stanton C. Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev. 2010;68(5):280-9.

[22] Dantzer R, O’connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9(1):46-56.

[23] Prat A, Biernacki K, Wosik K, Antel JP. Glial cell influence on the human blood-brain barrier. Glia. 2001;36(2):145-55.

[24] Skaper SD, Facci L, Giusti P. Mast cells, glia and neuroinflammation: partners in crime?. Immunology. 2014;141(3):314-27.

[25] Spiller R. Serotonin, inflammation, and IBS: fitting the jigsaw together?. J Pediatr Gastroenterol Nutr. 2007;45 Suppl 2:S115-9.

[26] Morand EF, Leech M. Hypothalamic-pituitary-adrenal axis regulation of inflammation in rheumatoid arthritis. Immunol Cell Biol. 2001;79(4):395-9.

[27] Hansen CH, Krych L, Buschard K, et al. A maternal gluten-free diet reduces inflammation and diabetes incidence in the offspring of NOD mice. Diabetes. 2014;63(8):2821-32.

[28] Antvorskov JC, Fundova P, Buschard K, Funda DP. Dietary gluten alters the balance of pro-inflammatory and anti-inflammatory cytokines in T cells of BALB/c mice. Immunology. 2013;138(1):23-33.

[29] Halliwell B. Antioxidants in human health and disease. Annu Rev Nutr. 1996;16:33-50.

[30] Holt EM, Steffen LM, Moran A, et al. Fruit and vegetable consumption and its relation to markers of inflammation and oxidative stress in adolescents. J Am Diet Assoc. 2009;109(3):414-21.

Paleo Diet and Inflammatory Bowel Disease: Are Emulsifiers to Blame?

We are often asked whether a Paleo diet can be a promising agent for the prevention and treatment of inflammatory bowel diseases. Impaired mucosal immunity in the gastrointestinal tract has been shown to lead to this debilitating condition.1 New data suggests that common food additives, called emulsifiers, could be contributing to the development of inflammatory bowel diseases, including colitis, by disturbing the composition of intestinal microbiota.2 This research has the ability to improve the health of 1-2 million people who suffer from ulcerative colitis,3 a major risk factor for colorectal cancer.4  Let’s take a closer look of how this research could impact Paleo dieters.

What role does intestinal microbiota play in reducing inflammatory conditions?

Gut microbiota is considered to be an organ within an organ,5 and provides many important benefits, especially in metabolism and immunity. In healthy individuals, the intestines are protected via multi-layered mucus structures that cover the intestinal surface, to keep a barrier between the epithelial cells that line the intestine and both healthy and pathogenic bacteria.6  Dysfunction of the relationship between the mucosal lining and bacteria results in low-grade inflammation that has been linked to promoting adiposity and contributing to negative metabolic effects,7 which can account for the increase in obesity and metabolic syndrome rates worldwide.8,9

Are emulsifiers sneaking their way into your Paleo Diet?

Emulsifiers are common food additives that impart creaminess, improve texture, extend shelf life, and emulsify oils in many processed foods. Emulsifiers and 1600 other food additives have been considered by the FDA to be “generally recognized as safe” (GRAS). It is alarming that there are this many processed substances are added to foods regularly consumed by Americans, without fully understanding the implications of these additives.10

Current research suggest emulsifiers in particular are in fact causing physical harm.11,12,13 They are often described to be like detergent – where the molecules lead to massive bacterial overgrowth,14 damage the mucosal lining, transport bacteria across epithelial tissue,15 and are cancer promoting.16 Hopefully, this evidence will encourage the FDA to perform further analysis and alter the criteria that has previously been used to evaluate food safety. Until then, further scientific evidence indicates it is best to avoid such processed foods as they contribute to the rise of modern diseases.

Although processed foods are not a part of a true Paleo Diet, many Paleo eaters still incorporate convenience foods containing them into their diet. These foods may include chocolate, mayonnaise, coconut and almond milk products, grain-free baked goods, protein powders, as well as many personal hygiene products like toothpastes and mouthwashes. To minimize the impact on your intestinal health and overall inflammation levels, avoid the following emulsifiers in any product you buy: xanthan gum, guar gum, carrageenan, cellulose gum, polysorbate 80, and (soy) lecithin.

In addition to being void of artificial emulsifiers, the foods eaten by traditional hunter-gathers are typically lower in carbohydrate than modern diets, and have also been linked to lower levels of inflammation of the gastrointestinal microbiota. Following a Paleo diet may lead to a microbiota that is more consistent with our evolutionary ancestors, and less likely to be impacted by the chronic inflammatory conditions linked to modern diets.17

Eat like our ancestors. Eat Paleo.

 

REFERENCES

[1] Middendorp, S., and E. E. S. Nieuwenhuis. “NKT cells in mucosal immunity.”Mucosal immunology 2.5 (2009): 393-402.

[2] Chassaing, Benoit, et al. “Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.” Nature 519.7541 (2015): 92-96.

[3] Colitis–Pathophysiology, Ulcerative. “Inflammatory bowel disease part I: ulcerative colitis–pathophysiology and conventional and alternative treatment options.” Alternative medicine review 8.3 (2003): 247-283.

[4] Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis.Gut. 2001;48:526–535.

[5] O’Hara, Ann M., and Fergus Shanahan. “The gut flora as a forgotten organ.”EMBO reports 7.7 (2006): 688-693.

[6] Johansson, M. E. et al. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Proc. Natl Acad. Sci. USA 105, 15064–15069 (2008)

[7] Bäckhed, Fredrik, et al. “The gut microbiota as an environmental factor that regulates fat storage.” Proceedings of the National Academy of Sciences of the United States of America 101.44 (2004): 15718-15723.

[8] Furet, Jean-Pierre, et al. “Differential Adaptation of Human Gut Microbiota to Bariatric Surgery–Induced Weight Loss Links With Metabolic and Low-Grade Inflammation Markers.” Diabetes 59.12 (2010): 3049-3057.

[9] Alberti, K. G. M. M., et al. “Harmonizing the Metabolic Syndrome A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.” Circulation 120.16 (2009): 1640-1645.

[10] Winter, Ruth. A consumer’s dictionary of food additives: Descriptions in plain English of more than 12,000 ingredients both harmful and desirable found in foods. Crown Archetype, 2009.

[11] Chassaing, Benoit, et al. “Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.” Nature 519.7541 (2015): 92-96.

[12] Tobacman, Joanne K. “Review of harmful gastrointestinal effects of carrageenan in animal experiments.” Environmental health perspectives 109.10 (2001): 983.

[13] Watt, J., and R. Marcus. “Harmful effects of carrageenan fed to animals.”Cancer detection and prevention 4.1-4 (1980): 129-134.

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