Teaser Excerpt from The Paleo Approach: What about the Goitrogens in Cruciferous Veggies?

April 25, 2013 in The Paleo Approach Excerpts

The Paleo Approach by Sarah BallantyneThere are many topics that I am researching and writing about for the book that I’ve been meaning to write about for the blog for ages (the book just gives me a firm deadline). I have decided take some of these topics (especially the more blog-sized ones) and publish them as teaser excerpts for the book (also because I think this information should be here too).

This excerpt is from Chapter 6, which is the Chapter that details exactly what foods to eat to heal from autoimmune disease (think of it as a 40ish page version of my Autoimmune Protocol post.  One of the challenges I have faced as I write this book is the need to understand what recommendations are broadly applicable and what exceptions there may be for specific autoimmune diseases.  And goitrogenic veggies is a pretty hot topic given the prevalence of autoimmune thyroid diseases (and an important one to get right).

This section comes after a lengthy rationale for eating a large amount and variety of vegetables and fruits, with an emphasis on eating the rainbow and trying to eat something green with every meal.

So, forgive the references to other chapters and page numbers with no number. While you’ll have to wait until the book is out in September to read those sections, in the meantime, please enjoy this part of Chapter 6: The Paleo Approach–Diet

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Those with autoimmune thyroid disorders (Hashimoto’s thyroiditis or Grave’s disease) and those with low thyroid function (which can often accompany other autoimmune diseases) are often advised to avoid consumption of cruciferous vegetables, spinach, radishes, peaches and strawberries due to their goitrogenic properties.  Goitrogens are any compound that  suppress the function of the thyroid gland by interfering with iodine uptake (recall that iodine is a necessary component of thyroid hormones, see page ##).  Thyroid hormones have essential roles in metabolism and even in regulation of the immune system, so supporting optimal thyroid function in everyone is important for healing and for general health.  But avoidance of these foods is actually not well justified.

The cruciferous family of vegetables (a.k.a. brassicas) comprises many of the most antioxidant-, vitamin- and mineral-rich vegetables available, including:

  • horseradish
  • land cress
  • kale, many varieties
  • collard greens
  • Chinese broccoli (gai-lan)
  • Cabbage, many varieties
  • brussels sprout
  • kohlrabi
  • broccoli, many varieties
  • broccoflower
  • broccoli romanesco
  • cauliflower
  • wild broccoli
  • bok choy
  • Mizuna
  • Komatsuna

  • Rapini (broccoli rabe)
  • flowering cabbage
  • napa cabbage (siu choy)
  • turnip, many varieties
  • rutabaga
  • canola/rapeseed
  • mustard, many varieties
  • tatsoi
  • arugula (rocket)
  • field pepperweed
  • maca
  • garden cress
  • watercress
  • radish, many varieties
  • daikon
  • wasabi

This family of vegetables is also particularly rich in a group of sulfur-containing compounds called glucosinolates (see page ##).  When these vegetables are chopped or chewed, an enzyme called myrosinase that is also present in these plants breaks the glucosinolates apart (through hydrolysis) into a variety of biologically active compounds, many of which are potent antioxidants and are known to prevent cancer.  Two of these antioxidant, anti-cancer classes of glucosinolate hydrolysis products are also known goitrogens.  These are isothiocyanates and thiocyanates.

Isothiocyanates and thiocyanates appear to reduce thyroid function by blocking the activity of the enzyme thyroid peroxidase (a.k.a. thyroperoxidase or TPO).  During thyroid hormone synthesis, TPO is the enzyme that catalyzes the transfer of iodine to a protein called thyroglobulin to produce either T4 thyroid prohormone (a.k.a. thyroxine) or the more active T3 thyroid hormone (a.k.a. triiodotyronine).  When isothiocyanates or thiocyanates are consumed in large enough quantities, this is how they interfere with the function of the thyroid gland (by inhibiting TPO).

Importantly, the evidence linking human consumption of isothiocyanates or thiocyanates with thyroid pathologies in the absence of iodine deficiency is lacking.  This means that these substances have only been shown to interfere with thyroid function in people who are also not consuming adequate amounts of iodine (if you are severely deficient in iodine or selenium, addressing those deficiencies before consuming large amounts of cruciferous vegetables is a good idea; see page ##).  In fact, the consumption of cruciferous vegetables correlates with diverse health benefits, including reducing the risk of cancer (even thyroid cancer!).  In a recent clinical trial evaluating the safety of isothiocyanates isolated from broccoli sprouts, no adverse effects were reported (including no reported reductions in thyroid function).

Perhaps even more compelling, at low concentrations (like what you would get just by including cruciferous vegetables in your diet), thiocyanates actually stimulate T4 synthesis, meaning that consuming these vegetables labeled as goitrogens may actually support thyroid function.  There is also a strong synergy between isothiocyanates and selenium in the formation of the very important enzymes thioredoxin reductase (see page ##) and glutathione peroxidase (see page ##).  This means that the consumption of isothiocyanates in conjunction with selenium is a tremendous support for the body’s antioxidant defense mechanisms and important for cancer prevention.  These are arguments for consuming more cruciferous vegetables, even for those with autoimmune thyroid diseases, not less, especially in the context of adequate dietary iodine and selenium.

Truly, the most important aspect of supporting thyroid function is providing the necessary minerals for thyroid hormone production, the most important of which are iodine, iron, selenium and zinc.  Deficiencies in any one of the minerals may impair thyroid function, but the effect of deficiencies is greatly magnified when more than one of these minerals are not available in adequate quantities.  Iodine is a necessary building block of thyroid hormones and the thyroid cannot function properly if insufficient iodine is available (see page ##).  Iron deficiency impairs thyroid hormone synthesis by reducing activity of TPO (which is heme-dependent, see page ##).  As already discussed in Chapter 3, selenium is required both for the conversion of the T4 thyroid prohormone (a.k.a. thyroxine) to the more active T3 thyroid hormone (a.k.a. triiodotyronine) because the enzymes responsible for this conversion (iodothyronine deiodinases) are selenoproteins.  Selenium is also essential to protect the thyroid gland from the effects of excessive iodide (excessive iodine inhibits the activity of TPO).  Zinc is believed to play an important role in thyroid metabolism, although the details remain unknown.  It appears to play a role in the conversion of T4 to T3 and zinc levels correlate with the levels of thyroid stimulating hormone (TSH), although the precise ramifications of zinc deficiency for thyroid function remain controversial.  All of these minerals are richly found in the foods included in The Paleo Approach.  Supplements are also discussed in Chapter 8.

Barrera, L.N., et al., TrxR1 and GPx2 are potently induced by isothiocyanates and selenium, and mutually cooperate to protect Caco-2 cells against free radical-mediated cell death, Biochim Biophys Acta. 2012 Oct;1823(10):1914-24

 Bonfig, W., et al., Selenium supplementation does not decrease thyroid peroxidase antibody concentration in children and adolescents with autoimmune thyroiditis, ScientificWorldJournal. 2010 Jun 1;10:990-6

 Bosetti, C., et al., A pooled analysis of case-control studies of thyroid cancer. VII. Cruciferous and other vegetables (International), Cancer Causes Control. 2002 Oct;13(8):765-75

 Chandler, J.D. & Day, B.J., Thiocyanate: a potentially useful therapeutic agent with host defense and antioxidant properties, Biochem Pharmacol. 2012 Dec 1;84(11):1381-7

 Ertek, S., et al., Relationship between serum zinc levels, thyroid hormones and thyroid volume following successful iodine supplementation, Hormones 2010, 9(3):263-268

 Hodkinson, C.F., et al., Preliminary evidence of immune function modulation by thyroid hormones in healthy men and women aged 55-70 years, J Endocrinol. 2009 Jul;202(1):55-63

Jakubíková, J., et al., Effect of isothiocyanates on nuclear accumulation of NF-kappaB, Nrf2, and thioredoxin in caco-2 cells, J Agric Food Chem. 2006 Mar 8;54(5):1656-62

 Magnusson, R.P., et al., Mechanism of iodide-dependent catalatic activity of thyroid peroxidase and lactoperoxidase, J Biol Chem. 1984 Jan 10;259(1):197-205

 McDanell, R., et al., Chemical and biological properties of indole glucosinolates (glucobrassicins): A review, Food and Chemical Toxicology. 1988; 26(1):59-70

 Shapiro, T.A., et al., Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study, Nutr Cancer. 2006;55(1):53-62

 van Bakel, M.M., et al., Antioxidant and thyroid hormone status in selenium-deficient phenylketonuric and hyperphenylalaninemic patients, Am J Clin Nutr. 2000 Oct;72(4):976-81

 Virion, A., et al., Opposite effects of thiocyanate on tyrosine iodination and thyroid hormone synthesis, Eur J Biochem. 1980 Nov;112(1):1-7

 Zimmermann, M.B. & Köhrle, J., The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health, Thyroid. 2002 Oct;12(10):867-78

The Benefits of Probiotics –Teaser Excerpt from The Paleo Approach

February 12, 2013 in Gut Health, Supplements, The Paleo Approach Excerpts

The Paleo Approach by Sarah BallantyneThere are many topics that I am researching and writing about for the book that I’ve been meaning to write about for the blog for ages (the book just gives me a firm deadline).  I have decided take some of these topics (especially the more blog-sized ones) and publish them as teaser excerpts for the book (also because I think this information should be here too).

The book also contains a detailed (yet easy-to-follow) description of the components of the immune system, so when you read the book, you’ll already know why modulating Th1 versus Th2 versus regulatory T-cells is important and you’ll know what dendritic cells, antigen presentation and cytokines are. For a quick primer: Th1 and Th2 cells are over-activated in autoimmunity and cause damage (typically one or the other is over-activated).  Regulatory T-cells are supposed to keep all the other immune cells in check and suppress both over-activation of the immune system and autoimmunity (they tend to be deficient in autoimmune disease).  Cytokines are chemical messengers of inflammation.  Dendritic cells are a type of sentinel cell that detects foreign invaders.  Antigens are small sequences of amino acids on foreign invaders that are recognized by the immune system.   When a dendritic cell detects foreign invaders, they “show” the antigens to B-cells and T-cells (cells of the adaptive immune system).  Gut-Associated Lymphoid Tissue is the collection of immune cells and other tissues just inside the intestinal barrier in the gut.  Enterocytes are the cells that line the small intestine and form the barrier between inside the gut and outside the gut.

So, forgive the references to Chapters 2, 3, 8 and 12.  While you’ll have to wait until the book is out in September to read those sections, in the meantime, please enjoy this part of my section of probiotics (actually, probiotics are talked about in 4 separate sections-this section is from the chapter on healing foods).

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Consumption of probiotics, either as a supplement or in the form of unpasteurized fermented foods, can dramatically help modulate the immune system.  A vast number of scientific and clinical studies have evaluated the various effects of the commensal bacteria in the gut (those healthy gut bacteria) and/or probiotic supplement of specific bacterial strains on various aspects of the immune system.  The cliff notes?  It’s all good.

The exact mechanisms behind the many observed benefits of probiotics remain largely unknown.  This may be because different bacterial strains have different effects on the body and interact differently with the immune system.  For example, some probiotic strains stimulate production of cytokines (those chemical messengers of inflammation) that promote Th1 cell development (which may augment the immune system to help fight infection and prevent cancer).  Other probiotic strains stimulate production of cytokines that promote regulatory T-cell development, thereby providing that all important immune system modulation needed in autoimmune disease (see Chapter 2).  Yet other probiotic strains, including several lactobacillus strains, are beneficial both in diseases of compromised immune systems and diseases of excessively activated immune systems.

It has been shown that probiotics interact with dendritic cells during antigen presentation during the initiation of adaptive immune responses, meaning that probiotics are useful in preventing immune-related diseases (see Chapter 2).  However, they also affect the effector phase of adaptive immunity, so they can be used as a treatment for established immune-related diseases (this applies to both immune-related diseases like asthma and allergies but also autoimmune diseases).  In fact, probiotic supplementation has been shown to be beneficial in a variety of autoimmune conditions, including:  autoimmune myasthenia gravis, inflammatory bowel diseases, rheumatoid arthritis, multiple sclerosis, and autoimmune thyroid disease.

It used to be believed that probiotic supplementation and the consumption of unpasteurized fermented foods provided health benefits by re-inoculating the gut with beneficial strains of bacteria and yeast.  Having a healthier variety and types of gut microorganisms would then be responsible for the positive benefits of probiotic supplementation.  However, recent scientific research puts this explanation into doubt—at least in some cases.  A recent study of diarrhea-predominant Irritable Bowel Syndrome demonstrated that the administration of probiotic supplements did not to alter the composition of the gut microflora.  It’s important to emphasize that probiotic supplementation was still beneficial.  This implies that the benefits of probiotic consumption might be directly due to the interaction of those probiotic bacteria (and yeast) with the gut-associated lymphoid tissue (see Chapter 2) as it passes through the body, at least in some cases.

There are clearly still some situations where probiotic supplements do have profound effects on the gut microflora.  For example, studies have shown differences in the composition of the gut microflora after taking antibiotics in people who supplemented with probiotics compared to those who didn’t.  There may also be more impactful effects on those with bacterial overgrowths.  Probiotic microorganisms have the capability to affect the gut microflora through a variety of mechanisms, including: reducing the acidity in the intestinal lumen (the area in the middle of the “tube” that forms the gut), competition for nutrients, secretion of antimicrobial compounds by the probiotics themselves, stimulating the production of antimicrobial compounds by your cells, and preventing adhesion and interaction of other bacteria with gut epithelial cells.  In these ways, probiotics may help to “correct” gut dysbiosis.

Beyond restoring balance to the gut microflora and modulating the immune system, research has shown that administration of probiotics can have a direct effect on the tight junctions between enterocytes in the gut—resulting in decreased intestinal permeability.  So, taking a probiotic or eating food naturally rich in probiotic organisms can directly help heal a leaky gut.

As already mentioned in Chapter 3, what you eat has a profound effect on the types, relative quantities and location of different bacteria growing in your gut—this effect is largely independent of the benefits of consuming fermented foods or taking probiotic supplements.  However, consuming probiotics has the great potential to speed healing and modulate the immune system and should not be underrated in importance when dealing with autoimmune disease.

Some researchers are taking on the task of characterizing the precise effects of each probiotic strain on the human body (recall that there are approximately 35,000 of them among all humans).  Certainly some strains have already been isolated for their anti-inflammatory and immune modulatory properties, yet others for their abilities to improve the barrier function of the gut or the ability to reduce visceral hypersensitivity.  It is completely possible that in the future, probiotic supplements will be tailored to address specific health problems by providing specific strains known to counteract those issues.  However, until then, the best focus is on variety.

Because different probiotic strains have slightly (and sometimes vastly) different effects (which may also depend on your genetics, level of inflammation, and current gut health), the best way to ensure complete modulation/regulation of the immune system is to consume as many different probiotic strains as possible.  So, where do you get variety?  You actually get far more variety from fermented foods and soil than you do from most supplement available (that doesn’t mean that probiotic supplements aren’t useful—see chapter 8 for more information specific to probiotic supplements).  Every time you make a new batch of homemade sauerkraut, the probiotic organisms within it will be slightly different.

So, what are good food sources of probiotics?

  • Raw unpasteurized sauerkraut
  • Raw unpasteurized lactofermented vegetables (kimchee, beets, carrots, pickles)
  • Raw unpasteurized lactofermented fruits (green papaya, chutneys)
  • Raw unpasteurized lactofermented condiments (relishes, salsas)
  • Water kefir
  • Milk kefir grown in coconut milk
  • Kombucha
  • Beet Kvass

Some form of probiotic should be consumed every day.  It is typically understood that a small amount several times per day is more beneficial than a large amount at one sitting.  When you first start consuming probiotic foods, it’s a good idea to keep the amount very small (as little as 1 teaspoon) and see how you feel.  Some people with severe gut dysbiosis can have dramatic gastrointestinal symptoms from probiotics.  If one probiotic food doesn’t work for you, try another.  If none of them work for you, you may have more luck with a supplement or just might need more time to heal your gut before introducing probiotics.  It’s okay if you need to follow The Paleo Approach for a couple of weeks before adding probiotic foods (for more information, see the Troubleshooting section in Chapter 9).  The amount you eat at any given time can then be slowly increased over the course of several weeks.  And of course, you can skip ahead to Chapter 12 to start making probiotic foods in your own home.

An often underrated source of probiotics is soil.  Soil-based organisms (SBOs) have not been as extensively studied as the lactobacillus and bifidus genus of bacteria.  However, they are normal residents of a healthy gut, have been shown to be potent modulators of the immune system, and supplementation with SBOs has been shown to be beneficial in diabetes, chronic fatigue syndrome, insomnia and Irritable Bowel Syndrome.  Soil-based probiotic supplements are available (see Chapter 8 for more information).  You can also get exposure by playing in the dirt (a good excuse to take up gardening as a hobby!) and by growing your own vegetables organically (or buying locally-grown organic vegetables) and eating them without washing them.  Okay, you can rinse the big clumps of dirt off.

 

Barbara, G., et al., Mucosal permeability and immune activation as potential therapeutic targets of probiotics in irritable bowel syndrome, J Clin Gastroenterol. 2012 Oct;46 Suppl:S52-5

Bittner, A.C., et al., Prescript-assist probiotic-prebiotic treatment for irritable bowel syndrome: an open-label, partially controlled, 1-year extension of a previously published controlled clinical trial, Clin Ther. 2007 Jun;29(6):1153-60.

Chae, C.S., et al., Prophylactic effect of probiotics on the development of experimental autoimmune myasthenia gravis, PLoS One. 2012;7(12):e52119.

Corridoni D, et al., Probiotic bacteria regulate intestinal epithelial permeability in experimental ileitis by a TNF-dependent mechanism, PLoS One. 2012;7(7):e42067

Fooks LJ and Gibson GR Probiotics as modulators of the gut flora. Br J Nutr 2002 88(Suppl 1):S39–S49.

Gerritsen, J. et al., Intestinal microbiota in human health and disease: the impact of probiotics, Genes Nutr. 2011 August; 6(3): 209–240.

Kiseleva, E.P., et al., The role of components of Bifidobacterium and Lactobacillus in pathogenesis and serologic diagnosis of autoimmune thyroid disease, Benef Microbes. 2011 Jun;2(2):139-54.

Kobayashi T, et al.,  Probiotic upregulation of peripheral IL-17 responses does not exacerbate neurological symptoms in experimental autoimmune encephalomyelitis mouse models, Immunopharmacol Immunotoxicol. 2012 Jun;34(3):423-33

Le Bert, N., et al., DC priming by M. vaccae inhibits Th2 responses in contrast to specific TLR2 priming and is associated with selective activation of the CREB pathway, PLoS One. 2011 Apr 1;6(4):e18346

Michail, S. & Kenche, H., Gut microbiota is not modified by Randomized, Double-blind, Placebo-controlled Trial of VSL#3 in Diarrhea-predominant Irritable Bowel Syndrome, Probiotics Antimicrob Proteins. 2011 Mar;3(1):1-7

Ng SC, et al., Mechanisms of action of probiotics: recent advances. Inflamm Bowel Dis. 2009;15(2):300–310.

Ruemmele F.M., et al., Clinical evidence for immunomodulatory effects of probiotic bacteria, J Pediatr Gastroenterol Nutr. 2009 Feb;48(2):126-41.

Shida, K. & Nanno, M., Probiotics and immunology: separating the wheat from the chaff, Trends Immunol. 2008 Nov;29(11):565-73.

Shida K, et al., Flexible cytokine production by macrophages and T cells in response to probiotic bacteria: a possible mechanism by which probiotics exert multifunctional immune regulatory activities, Gut Microbes. 2011 Mar-Apr;2(2):109-14

Schiffer, C., et al., A strain of Lactobacillus casei inhibits the effector phase of immune inflammation, J Immunol. 2011 Sep 1;187(5):2646-55

Tlaskalová-Hogenová, H., et al., Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases, Immunol Lett. 2004 May 15;93(2-3):97-108.

Tsilingiri K & Rescigno M., Postbiotics: what else?, Benef Microbes. 2012 Dec 27:69-75.

Soil-based organisms improve immune function: shift cytokine profile from TH2 to TH1, Posit Health News. 1998 Spring;(No 16):16-8

http://www.old-herborn-university.de/literature/books/OHUni_book_8_article_4.pdf