Teaser Excerpt from The Paleo Approach–The Importance of Sleep

April 4, 2013 in Practical Tips, Stress and Sleep, 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, including a great quick reference guide to help you as you read through the book.  So, when you read this section in the book, you’ll already know why modulating Th1, Th2 and Th17 cells is important and you’ll already understand the essential role that regulatory T-cells play in the immune system.  

For a quick primer: Th1, Th2 and Th17 cells are subtypes of lymphocytes (white blood cells) that can be over-activated in autoimmune disease and cause damage. Regulatory T-cells are another subtype of lymphocyte that 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. Monocytes and neutrophils are types of white blood cell responsible for generalized inflammation (part of the innate immune system whereas B-cells and T-cells are part of the adaptive immune system).  B-cells are the type of lymphocyte that produce antibodies.

So, forgive the references to Chapter 7 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 4:  Lifestyle Factors That Contribute to Autoimmune Disease.

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“A good laugh and a long sleep are the best cures in the doctor’s book.”

–Irish Proverb

In the last 50 years, the average amount of time that Americans sleep each night has decreased by 1.5–2 hours.  That’s a staggering amount of sleep—equivalent to a full month of continuous sleep every year—that we need but are not getting.  Epidemiological studies show a strong correlation between short or disturbed sleep and obesity, diabetes and cardiovascular disease.  In fact, lack of adequate sleep has been associated of increased morbidity and mortality from all causes.  This means that if you consistently don’t get enough sleep, you have a much higher risk of getting sick and/or dying.  Period.  Studies have also evaluated the role that sleep plays in healing from specific diseases, like breast cancer, and show that the less you sleep, the less likely you are to survive.

Frankly, scientists still don’t really understand why we need sleep, why we need as much as we do, and what our bodies are actually doing while we sleep.  But, it is obvious that sleep is important for human health.  Studies that evaluate the physiological changes caused by not sleeping or not getting enough sleep can be very instructive in understanding just how critically important sleep is.  For those with autoimmune disease, it is especially important to understand the role that sleep has in inflammation, stimulating the immune system, and regulating hormones (which themselves modulate the immune system).

Just plain old not getting enough sleep causes inflammation even in young, healthy people.  A variety of studies evaluating the effects of acute sleep deprivation (typically by restricting sleep to 4 hours per night) for several consecutive days (typically 3 to 5) have shown increases in markers of inflammation and the numbers of white blood cells in the blood.  Specifically, even just three consecutive nights of not enough sleep can cause increased monocytes, neutrophils and B-cells in the blood, increased proinflammatory cytokines (including cytokines known to stimulate maturation of naïve T-cells into Th1, Th2, and Th17 cells), increased C-reactive protein (a marker of inflammation), increased total cholesterol and increased low density lipoprotein cholesterol (LDL).

Even just one night of lost sleep (40 hours without sleep) causes inflammation in young, healthy people.  Just pulling a single all-nighter dramatically increases markers of inflammation in the blood, including C-reactive protein and proinflammatory cytokines.  Studies that evaluated not just sleep deprivation but also recovery after sleep restriction (with the idea of simulating a typical workweek where someone might get less sleep for 4 or 5 nights straight and then try to make up for it on the weekend) have also shown that the proinflammatory cytokine known to stimulate Th17 cell development persists for at least two days after increasing sleep to 8 hours per night, even though other markers of inflammation have recovered.  This means that even if you try and “catch up” on your sleep during the weekend, the stimulation to the immune system keeps going.  If you follow this stereotypical pattern of not getting enough sleep during the week and sleeping in on the weekend, you still run the risk of cumulatively causing detrimental changes in the immune system.  Certainly, you can recover from lack of sleep, but it takes persistence, consistency and commitment—even during the week.

Sleep deprivation is also associated with increased susceptibility to infection.  In fact, the less sleep you get, the more likely you are to catch the common cold.  Getting adequate sleep can also protect you from infection.  One study even showed that the longer the sleep duration, the lower the incidence of parasitic infections in mammals.

Inadequate sleep also has profound effects on hunger hormones and metabolism (recall that hunger hormones such as insulin, leptin, ghrelin, and cortisol are important modulators of the immune system, see page ##, ## and ##).  For example, when food intake is measured following sleep deprivation (5 consecutive days of 4 hours sleep), people tend to eat substantially (20%!) more than normal.  However, it doesn’t take five full days of inadequate sleep to see dramatic effects on insulin, cortisol, and leptin.  One study showed that even a single night of partial sleep (4 hours) causes insulin resistance in healthy people.  Another study showed that a single night of partial sleep (3 hours, in this case) caused reduced morning cortisol levels (when cortisol should be its highest) and elevated afternoon/evening cortisol (when cortisol should be gradually decreasing) and elevated morning leptin levels.  This means that one night of three or four hours sleep causes insulin resistance, dysregulated cortisol and increased leptin.  One late bedtime because you went to a late night movie or a party at the boss’ house.  One.

Inadequate sleep has also been investigated as a possible cause of autoimmune disease. In an animal model of psoriasis, sleep deprivation caused significant increases in proinflammatory cytokines, cortisol levels, and increases in specific proteins in the skin associated with symptoms of psoriasis (like the flaking, dry, scaly skin).  In an animal model of multiple sclerosis, mice subjected to sleep deprivation developed the disease earlier than mice that slept normally.  Once the mice developed multiple sclerosis, sleep deprivation caused increased disease activity and pain sensitivity.  Furthermore, sleep disturbances are commonly reported by people with chronic inflammatory conditions (such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease and asthma).  Whether the sleep disturbances cause the disease or the disease causes the sleep disturbances is not well understood.  However, such sleep disturbances are known to worsen the course of the disease, aggravate disease symptoms such as pain and fatigue, increase disease activity and lower quality of life.  Yes, sleep is important.

So, how much sleep do you need?  There is no clear answer to this.  Consensus is that healthy adults need 7-10 hours of sleep per night.  If you are trying to heal from an autoimmune disease, don’t be surprised if what your body needs is on the longer end of that range (say 9 to 10 hours) or even exceeding that range (some people with autoimmune disease report needing 12 hours of sleep every night to heal).

Getting enough sleep isn’t just about preventing inflammation; it’s also about repairing the body and modulating the immune system.  Certainly, the process of tissue repair in the body is predominantly performed during sleep.  However, an important study showed that regulatory T-cell activities follow a circadian rhythm, meaning that, just like many functions within the human body, they increase and decrease throughout the day.  In healthy people, regulatory T-cells are highest in the blood at night with lowest numbers in the morning (similar to melatonin production and the opposite of cortisol). The activity of the regulatory T-cells also follows a circadian rhythm, having the highest suppressive activity during sleep and lowest in the morning.  When volunteers were subjected to sleep deprivation, the suppressive activity of their regulatory T-cells was decreased (even though the actual numbers of T-cells remained the same).  This implies that sleep is required for the suppressive activity of regulatory T-cells, meaning that if you want to modulate your immune system and reverse your autoimmune disease, sleep is critical.

If you have an autoimmune disease (I generally assume you do if you are reading this book) and aren’t getting 8 hours of good sleep every night, I cannot emphasize enough the importance of putting sleep on the top of your priority list.  You need sleep.  Now.  Tonight.  Every night.  Seriously, stop reading and go to bed.  Strategies for prioritizing sleep and what to do if you are trying to get more sleep but just can’t are discussed in Chapter 7.

Bollinger, T., et al., Sleep-dependent activity of T cells and regulatory T cells, Clin Exp Immunol. 2009 Feb;155(2):231-8

Bosy-Westphal, A., et al., Influence of partial sleep deprivation on energy balance and insulin sensitivity in healthy women, Obes Facts. 2008;1(5):266-73

Boudjeltia KZ, et al., Sleep restriction increases white blood cells, mainly neutrophil count, in young healthy men: a pilot study, Vasc Health Risk Manag. 2008;4(6):1467-70.

Donga, E., et al., A single night of partial sleep deprivation induces insulin resistance in multiple metabolic pathways in healthy subjects, J Clin Endocrinol Metab. 2010 Jun;95(6):2963-8.

Frey, D.J., et al., The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults, Brain Behav Immun. 2007 Nov;21(8):1050-7

Heslop, P., et al., Sleep duration and mortality: The effect of short or long sleep duration on cardiovascular and all-cause mortality in working men and women, Sleep Med. 2002 Jul;3(4):305-14.

Hirotsu, C., et al., Sleep loss and cytokines levels in an experimental model of psoriasis, PLoS One. 2012;7(11)

Lehrer S, et al., Insufficient sleep associated with increased breast cancer mortality, Sleep Med. 2013 Mar 4 pii: S1389-9457(12)00384-X. doi: 10.1016/j.sleep.2012.10.012. [Epub ahead of print]

Lucassen EA, et al., Interacting epidemics? Sleep curtailment, insulin resistance, and obesity, Ann N Y Acad Sci. 2012 Aug;1264(1):110-34

Meier-Ewert HK, et al., Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk, J Am Coll Cardiol. 2004 Feb 18;43(4):678-83.

Palma, B.D., et al., Effects of sleep deprivation on the development of autoimmune disease in an experimental model of systemic lupus erythematosus, Am J Physiol Regul Integr Comp Physiol. 2006 Nov;291(5):R1527-32.

Palma, B.D. & Tufik, S., Increased disease activity is associated with altered sleep architecture in an experimental model of systemic lupus erythematosus, Sleep. 2010 Sep;33(9):1244-8.

Ranjbaran, Z., et al., The relevance of sleep abnormalities to chronic inflammatory conditions, Inflamm Res. 2007 Feb;56(2):51-7.

Reynolds AC, et al., Impact of five nights of sleep restriction on glucose metabolism, leptin and testosterone in young adult men, PLoS One. 2012;7(7)

van Leeuwen WM, et al., Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL-17 and CRP, PLoS One. 2009;4(2)

TPV Episode 28 Show Notes: Immune System and Immune Disorders

March 1, 2013 in Show Notes

Our twenty-eighth show!
Ep. 28: Immune System and Immune Disorders

In this episode, Stacy and Sarah are not talking about autoimmune disorders, but the opposite: how do you handle a taxed or a disordered immune system? Hear tips on how to regulate immune function and how to recover when you’ve been sick. Plus, should you really give children wheat so that they develop  immune tolerance to it?

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A New Study Has the Media Buzzing About Gluten. Again.

February 25, 2013 in For Babies, Paleo Philosophy, Practical Tips, Topics for Paleo Families

A new study in the journal Pediatrics has the gluten-free/celiac disease world buzzing (this article has been published on dozens of websites).  The study concludes that early introduction of small amounts of gluten while still breastfeeding reduces the risk of celiac disease.

The study looked at two cohorts of Swedish 12-year olds, the first were a group born in 1993 during an epidemic of celiac disease (during the epidemic, the incidence of celiac disease increased from 1 in 100 to 3.3 in 100, believed attributable to changes in government recommendations for the age of gluten introduction to 6 months old, combined with a concurrent increase in the gluten content of baby foods) and the second were a group born in 1997 after the epidemic (after the government revised their guidelines to lower the age of gluten introduction to 4 months and the amount of gluten in baby foods was reduced).  The study sought to determine the impact of breastfeeding in relation to gluten introduction on the future development of celiac disease.

The hypothesis of the study is well summarized in this statement from the discussion section.

“Oral tolerance to an antigen develops early in life, and celiac disease can be viewed as a failure to develop oral tolerance to gluten, or a later loss of this tolerance.  The development of oral tolerance is a complex immunologic process involving interactions between genetic factors and environmental and lifestyle exposures, such as bacterial gut colonization and infant feeding.”

And this idea is what has my inbox flooded with questions.  If oral tolerance for gluten develops early in life and breastfeeding helps with the development of oral tolerance, is it better to give our paleo babies some gluten now?  Will that help prevent celiac disease and other autoimmune diseases?

To answer this question, let me first summarize exactly what this paper shows about the relation between breastfeeding, gluten introduction and celiac disease.  Over 13000 children were enrolled in the study.  The incidence of celiac disease was 2.8 in 100 in the 1993 cohort versus 2.2 in 100 in the 1997 cohort.  The median age of gluten introduction was the same (5 months old) between both cohorts.  But, the infants in the 1997 cohort were breastfed an average of 2 months longer than the 1993 cohort (age of weaning increased from an average of 7 months to an average of 9 months between 1993 and 1997).  What this means is that the number of babies who were breastfed during and beyond gluten introduction was significantly larger in the 1997 cohort (number of babies breastfed beyond gluten introduction was 70% vs 78% in the 1993 and 1997 cohorts, respectively).  From this, the authors conclude that introducing gluten before weaning reduces the risk of celiac disease.

24GLUTEN-articleInlineThis is an interesting observation and I think that this Op Ed piece in the NY Times provides a possible explanation for the result that is not thoroughly discussed in the original paper:  it’s all about the gut microbiota.

The most current understanding of celiac disease (well summarized in this paper, which sadly requires a subscription to view) is that the development of celiac disease (and indeed all autoimmune diseases) relies on three factors:

  1. Genetic predisposition
  2. Environmental trigger (in the case of celiac disease, that trigger is gluten)
  3. A leaky gut and/or gut dysbiosis

All three of these factors work together to develop autoimmune disease.  In terms of celiac disease, the genetic predisposition is at least partially understood: 90% of celiacs have one of two variants of the HLA gene (either DQ8 or DQ2).  What you need to know about the HLA gene is that it (or more specifically the protein in encodes) is involved in antigen presentation to the adaptive immune system, and defects in this process seem to be permissive for autoantibody formation.  But, approximately 30% of us have one of these gene variants and only 1% of us develop celiac disease (it should be noted that these gene variants are linked to other autoimmune diseases as well as non-celiac gluten sensitivity, so it’s not like the other 29% of us are getting off easy).  The environmental trigger for celiac disease is dietary gluten (or more specifically the protein fraction of gluten, called gliadin).  So, what’s the wild card?  A leaky gut.  And the development of a leaky gut may be what determines the age of disease onset, which is highly variable.  Chance (or maybe previous infections or maybe gut dysbiosis, i.e., the wrong types of bacteria growing in the wrong numbers in the wrong part of the gut) may be what determines whether a person develops celiac disease versus another autoimmune disease versus other health problems linked to gluten.

A leaky gut can be caused by a wide variety of factors, including: diets rich in some types of lectin (like gluten) and saponins (especially glycoalkaloids), stress, and gut dysbiosis (especially bacterial overgrowths).  Gut dysbiosis itself can be caused by diets rich in processed foods, refined carbohydrates, some types of lectins (especially prolamins like gluten and agglutinins like wheat germ agglutinin) and saponins (especially glycoalkaloids), by some medications (such as PPIs and antibiotics) and by stress.  A leaky gut and gut dysbiosis go hand in hand and it is not known which comes first.

So, what is the link between breastfeeding and a leaky gut?  The link is really to gut dysbiosis (or lack thereof).  Studies show that breastfeeding is important for the establishment and growth of normal gut microorganisms.  In particular, breastmilk contains probiotics (from strains shown to be deficient in the guts of those with celiac disease) and for the duration of breastfeeding, the guts of babies are being constantly inoculated with these beneficial bacteria.  It is becoming increasingly recognized that the healthy diversity and relative amounts of gut microorganisms are intricately linked your health.  So, it’s no surprise that whatever factors contribute to healthy gut microorganisms in babies will protect them from disease.

So, let’s get back to the study.  It has one very big limitation relevant to this discussion.  It cannot separate whether the exact age of gluten introduction in babies who were breastfed longer has any effect on celiac risk.  This study definitely shows that breastfeeding longer decreases celiac risk.  But, the idea that this is because breastfeeding occurred during and beyond gluten introduction is speculative.  It certainly makes sense given other research on the link between gut microorganisms and disease risk that a healthy gut is important in celiac disease risk and that breastfeeding longer improves the health of the gut microorganisms.  But, this study just can’t tell you whether introduction of gluten early (and before weaning) is important.  If the reason breastfeeding is protective is because of its probiotic effects (it’s nutrient value would be another good reason), then it could be that it doesn’t matter when gluten is introduced (if ever) as long as the gut is healthy when you do.

From birth through adulthood, diet has a profound effect on the composition and relative quantities of your gut microorganisms (I explain this is detail in my book).  And healthy gut microorganisms have a profound protective effect on the integrity of the gut barrier and are essential modulators of the immune system (yes, I explain this in detail in my book as well).  The optimal diet in terms of gut and gut microorganism health seems to be a hunter/gatherer/gardener type diet, rich in plants (but not grains or legumes and nothing processed or refined) and wild or pastured meat and/or wild-caught fish (no surprise to us in the paleo community).   What is healthy nutrient-dense food for you just happens to be healthy food for your gut microorganisms.  And, while this is an oversimplification, if you feed your gut bacteria good food, they are healthy, and therefore you are healthy.

So, getting back to the question that is flooding my inbox:  does this paper mean you should feed your paleo babies a little gluten now so that they will develop immune tolerance?  This study does not allow us to conclusively say yes or no.  Certainly, this study does not prove its assertion that introducing small amounts of gluten into the diet very early and prior to weaning will increase immune tolerance and therefore protect your baby against ever developing celiac disease (although you can add this study to the bounty of scientific studies showing that breastfeeding is beneficial for your baby). It should also be noted that the health of the mother greatly affects the probiotic and nutrient content of the breastmilk.  It is unknown whether breastmilk is still protective in the context of obese mothers or mothers with chronic health conditions.

I believe that the best thing that you can do for your baby’s long term health (besides love and cherish them) is feed them nutrient-dense, nourishing foods that will help them have healthy guts and healthy gut microorganisms.  I do not believe that gluten consumption promotes a healthy gut or healthy gut microorganisms (and the science backs me up on this one—I reference a few hundred studies on this topic in my book).  But, I also don’t know whether, if you wait “too long” to introduce gluten, if some magical window of opportunity to develop immune tolerance against gluten will be missed (or how much gluten you would need to keep in the diet to maintain immune tolerance).  I also don’t know whether having immune tolerance against gluten is even a good thing in terms of overall long term health.  Science does not yet provide a clear answer.  So, with all of these ideas in mind, the decision will have to be yours and will have to be based on your own risk assessment.

Bengmark S. Gut microbiota, immune development and function. Pharmacol Res. 2013 Mar;69(1):87-113. doi: 10.1016/j.phrs.2012.09.002. Epub 2012 Sep 16.

Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012 Feb;42(1):71-8. doi: 10.1007/s12016-011-8291-x.

Groschwitz KR and Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009 Jul;124(1):3-20; quiz 21-2. doi: 10.1016/j.jaci.2009.05.038.

Hascoët JM et al. Effect of formula composition on the development of infant gut microbiota. J Pediatr Gastroenterol Nutr. 2011 Jun;52(6):756-62. doi: 10.1097/MPG.0b013e3182105850.

Ivarsson A et al Epidemic of coeliac disease in Swedish children. Acta Paediatr. 2000 Feb;89(2):165-71.

Ivarsson A, Prevalence of Childhood Celiac Disease and Changes in Infant Feeding. Pediatrics. 2013 Feb 18. [Epub ahead of print] http://pediatrics.aappublications.org/content/early/2013/02/13/peds.2012-1015.long

TPV Episode 27 Show Notes: Mark Sisson and the Primal Connection

February 22, 2013 in Show Notes

Our twenty-seventh show!
Ep. 27: Mark Sisson and the Primal Connection

In this episode, Stacy and Sarah are joined by the fabulous Mark Sisson! Mark’s new book, the Primal Connection talks about how to reconnect to the rest of your genes and ancestral heritage after you’ve accomplished the big diet and exercise goals. It was a fascinating discussion we are sure you will love too!

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The Paleo View (TPV), Episode 27: Mark Sisson and the Primal Connection

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