Caring for the Caregiver: Mind Your MTHFR! by Julie A. Buckley, MD

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Julie A. Buckley, MD, FAAP, is a graduate of the University of Miami School of Medicine and of the Jackson Memorial Hospital/ University of Miami Pediatric Residency Program, Dr. Buckley developed an abiding interest in autism spectrum disorders when her daughter regressed into the world of autism at four years of age. She developed a similar interest in breast cancer when she developed it herself in 2009. Using an integrative/functional medicine approach to both diseases, both mother and daughter have had dramatic recoveries. As a result of these successes, this approach has been implemented into her unique and diverse practice in Ponte Vedra Beach, Florida. Dr. Buckley is the author of the book Healing Our Autistic Children, which was released in September 2009, and she speaks internationally on autism and related disorders. She has also developed a patented antioxidant formula for peri-vaccination and peri-oxidative stress use. Dr. Buckley co-founded HEAL! (Healing Every Autistic Life!), a 501c3 non-profit foundation, and more recently has founded HealthyUNow Foundation, a 501c3 non-profit foundation dedicated to creating facilities for individuals and their families impacted by autism.
Caring for the Caregiver: Mind Your MTHFR!
IntroductIon Evidence mounts for autism being a whole-body medical illness that is environmentally influenced with a role for genetic vulnerability. As parents of children with regressive autism, we need to remember that the apple usually doesn’t fall very far from the tree. While we care for children whose disease surprises us daily with its manifestations, and while we innovate our children’s treatments because of autism’s relative newness to the medical world, the inevitable stress of raising our children takes a toll on us, the caregivers. If we are to avoid becoming ill ourselves, we must actively maintain our health as a vital entity—something more than just the absence of disease. defInIng autIsm The model of autism as a medical disease began with Leo Kanner’s descriptions of his 11 patients. Somehow, Kanner’s broader perspective quickly fell by the wayside when experts instead filed autism in the psychiatric disease file drawers. Dr. Sidney Baker, surely one of the wisest and most astute clinicians to ever walk this planet, described the disease beautifully and drew attention back to its medical aspects when he put autism spectrum disorders (ASDs) at the center of a Venn diagram (see Figure 1). Those of us who work in autism are taught initially that autism lies at the intersection of three Venn diagram sets: behavioral problems, social skills problems, and communication problems. In the last decade-plus, though, a broadening of our understanding has added a second group of sets that we now consider to also be at issue in autism: bowel disease with its diverse manifestations, immune dysregulation in its myriad presentations, and methylation chemistry disruption with its devastating impact on folate chemistry and glutathione production. (The first two were aptly described long ago by Kanner; the third took the arrival of Jill James and her research to round out what clinicians were observing.) More recently, functional medicine has reminded us of a great truth that gives us a third group of sets for our more comprehensive Venn diagram: toxicants (things placed into the body that should not be there) and the two bodily processes that toxicants will nearly universally create, namely, a chronic inflammatory response and oxidative stress. The successful treatment of autism as a whole-body medical disease lies in addressing the second and third groupings of sets. What is amazing is that when we do that, the behavioral manifestations of autism (the first group of sets) tend to take care of themselves.
Turning to the methylation chemistry disruption component of the second group of Venn diagram sets, the work of Jill James elucidated the critical role of methylenetetrahydrofolate reductase (MTHFR) in autism risk and autism management. MTHFR creates activated folate, which is critical to neurotransmitter function, among other things. MTHFR also creates a free methyl group that is donated to the vitamin B-12 we eat, making methylcobalamin. Methylcobalamin is imperative in supporting the body’s synthesis of glutathione, which is our master antioxidant and innate manager of oxidative stress. When this methylation process works normally, we make glutathione as we should. When, however, this methylation process does not work optimally, we refer to the problem as “hypomethylation.” Sufficient exposure to toxicants can compromise the function of MTHFR and cause hypomethylation in anyone. However, genetic vulnerability makes it much easier for MTHFR function to be affected. Interestingly, whereas the incidence of genetic vulnerabilities in MTHFR is estimated to be between 42% and 56% in the uS population as a whole,1 the numbers are at least 1.7-fold higher in the autism population.2 One retrospective review of charts found that 98% of children with autism had at least one polymorphism in the MTHFR gene. 3 This higher incidence is inherited from the parents, and therein lies the caregiver’s rub. chronIc stress as a toxIcant As caregivers to children with autism, we are familiar with the Venn diagram of our children’s disease, and we are often adept at juggling the interventions our children require in the pursuit of recovery. What we forget, though, is that our children acquired their genetic vulnerabilities from us! When we incur chronic stress in caring for our children, the stress acts as a toxicant and induces a chronic inflammatory response and oxidative stress in our own bodies. As genetically vulnerable caregivers, we may then struggle, like our children, to synthesize activated folate, methylcobalamin, and, ultimately, glutathione. Lowered glutathione can be expected to have an impact on our immune, bowel, and detoxification functions and compound the problem of vulnerable methylation pathways, just as it does in our children. It is common knowledge that emotional stress increases sympathetic “fight or flight” hormone release and that this is not good for us when it happens chronically. Research into caregivers as a medical entity is showing that stress is actually proinflammatory4 and impacts our immune function5 as well as inducing oxidative stress. 6,7 Emotional stress also lowers gastric motility and increases colonic motility,8 affecting bowel function. In short, stress as a toxicant produces a cascade of effects in our bodies similar to what our children experience. Research also shows us that one of the consequences of hypomethylation is to shorten the telomeres on our DNA.9 Telomeres are like the guards at either end of tightly packed DNA. If telomeres are poorly methylated, they shorten. Shortening of the telomeres is associated with aging. Telemere shortening also allows our normally tightly coiled and quiescent DNA to unpack, much like opening the proverbial “Pandora’s box,” and allows unexpressed disease genes to begin to express themselves. With our vulnerable methylation pathways, exposure to chronic stress will not cause us to develop autism but will cause us to age much more quickly and will allow chronic illnesses that are encoded on our individual DNA to manifest. The longer that high-stress caregiving goes on, moreover, the more significant will be the oxidative stress and telomere shortening that we experience, and the faster the aging.9
makIng the caregIver a prIorIty As I learned personally in 2009 when I developed breast cancer (and then added “cancer survivor” to my list of life accomplishments), it is much more difficult to be helpful to our children when we as caregivers are sick than when we are well. Although this may seem painfully obvious, the reality is that, when it comes to taking care of our own health, we tend to put ourselves second (at best) or, more commonly, dead last in the family. However, given that our children have a disease that often requires years of treatment and therapy, we would be wise to begin taking care of ourselves so that we can be present for our children over the long-term. Of course, we know that anything we do for ourselves needs to be readily accomplished within the busy context of caring for our children. It mustn’t take extra time away from our precious sleep, it must be free (or virtually so), and it must be compatible with frequent interruptions! Fortunately, this is not as impossible as one might think, especially given what we have learned from our children as we restore their health. Basic techniques are available that we can use even in our highly specialized lives of pandemonium and chaos. These include food, sleep, exercise, supplementation, and relaxation. FOOD Perhaps the most important medicine of all is the food we eat. It is critically important that we nourish ourselves just as we do our children and model the diet we want our children to eat. It’s amazing how differently the body will feel and respond. We are already well aware of the proinflammatory nature of gluten and casein as well as their ability to form circulating opiates in our bloodstreams. Why, then, do we resist eliminating them? We also know that carbohydrate overload promotes dysbiosis and makes for blood sugar highs and lows throughout the day. And we know that vegetables are good for us, organic foods are much more nutrient-rich than non-organic foods, and that the fats in nuts and seeds are the healthy fats that nourish our brains. Table 1 summarizes some of these simple rules.
table 1. Dietary principles for caregivers and children
1 “Eat your colors.” (The person who gave me this advice accompanied it with the admonition that “they need to be the colors that God gave the food, not a color manufactured in a factory.”) 2 Eliminate gluten and casein. 3 Eat fewer of the “white” foods that turn too quickly to sugar. 4 Make organic choices to the extent that your budget will allow. This is especially important with the so-called dirty dozen (those fruits and vegetables that absorb the highest amounts of toxins when grown conventionally). 5 Choose more veggies and fewer fruits. 6 Chew on some seeds and have some nuts.
Perhaps the most important medicine of all is the food we eat. It is critically important that we nourish ourselves just as we do our children and model the diet we want our children to eat.
Exercise may well be one of the most important things we can do for ourselves. In addition to helping with sleep, exercise boosts energy levels, regulates appetite, regulates weight, modulates our immune function, and regulates mood.
SLEEP Another area we tend to neglect is our sleep. When our children sleep (if they sleep), we often stay up late reading about how to help them. However, our bodies do significant healing as we rest. It’s crucial to make sure that the entire household, including us, is sleeping well. For those caregivers with their own sleep difficulties, a little melatonin is known to help start sleep, and often some 5HTP will continue it. It is also important to remember that exercise improves the quality of our sleep.10 EXERCISE Exercise may well be one of the most important things we can do for ourselves. In addition to helping with sleep, exercise boosts energy levels,11 regulates appetite,12 regulates weight,13 modulates our immune function,14 and regulates mood.15 It isn’t necessary to join a gym to get exercise. Walking is one of the cheapest and most sustainable forms of exercise there is, and the only equipment you need is a pair of sneakers. When I was taking my son to the orthodontist, those half-hour early morning appointments never went to waste; instead of sitting in the waiting room, I went to the parking lot and walked the perimeter as quickly as I possibly could, getting my heart rate up and my body moving. Some of us do much better sustaining exercise when we hold ourselves accountable in some fashion. One easy way to do that is to sign up for the 5K walk/run races that are prevalent all over the nation these days. If we know we have an upcoming event, we may be more likely to “train” for it. moderate and vIgorous exercIse Public health authorities teach us that we should get 150 minutes of moderate exercise or 75 minutes of vigorous exercise each week. To understand what “moderate” and “vigorous” exercise mean for us, we first need to be able to calculate our maximum heart rate (MHR). This is done by subtracting our age from 220. The result is our MHR. Moderate exercise is activity that gets your heart rate up and sustained at 50-70% of your MHR. To find your moderate exercise heart rate, first multiply your MHR by 0.5 (MHR x 0.5) and then by 0.7 (MHR x 0.7). The two answers give you the range your heart rate should stay in through the course of your exercise session. Vigorous exercise is the term used for exercise that has a sustained heart rate between 70- 85% of our MHR. To find the heart rate you need to sustain for vigorous exercise, multiply your MHR by 0.7 (MHR x 0.7) and again by 0.85 (MHR x 0.85). This will provide you with your range for vigorous exercise. Once you know what your numbers are, it’s important to get out there and make sure you’re actually raising your heart rate! SUPPLEMENTATION The topic of supplementation tends to be subject to the most discussion. In an ideal world, we would be able to eat all the necessary vitamins and minerals our bodies need in our foods. However, there are a few things that we must remember when making that promise to ourselves. First, to be successful in meeting our needs with food alone, we would have to eat a primarily organic fresh green-leafy plant-based diet. We would have to avoid all additional stressors to our bodies that might increase our body’s needs for vitamins and minerals on a day-to-day basis. We would have to avoid any environmental stressors that might increase our body’s needs for antioxidants or antiinflammatories. unfortunately, there are very few folks who are able to do those things. The next thing we need to remember is that the Daily Value numbers listed on the nutritional labels we inspect so carefully are not “optimal” recommendations. Those daily values are actually the minimal amount of each nutrient that is required by the average healthy human body in order to avoid developing a deficiency disease state. I know that my personal needs change from day to day. If I’m relaxing at home, eating my home-cooked organic food, and all is right in my world, my needs are less. If I work a full day at the office and jump on a plane to go to speak at a conference on the other side of the country, my nutritional needs are significantly higher. Armed with that knowledge, what, if any, supplements should we caregivers take, and which supplements should we avoid? The list of what might be useful is very long, but for the purposes of this discussion, I’ll keep the list deliberately short and focus on the least expensive supplements that offer the greatest “bang for the buck.” Antioxidants: First, enhancing our antioxidant status and reducing our oxidative stress is crucial. Vitamin c is a safe and inexpensive antioxidant that is readily available. Generally speaking, buffered forms are probably the best choice, and doses from 500 mg to several thousand milligrams daily are often safe, depending on the individual situation. At the same time, from an antioxidant standpoint, avoiding the use of acetaminophen is important because acetaminophen lowers glutathione synthesis.16 We’re accustomed to using acetaminophen-containing products to reduce fever and pain when we are sick, but, ironically, when we’re sick is the time when we need all of the glutathione we can make. N-acetyl-cysteine (NAc) is another inexpensive antioxidant, but it is thought to worsen dysbiosis, meaning that it may not be a good choice if your bowel is not robust and healthy. Vitamin D3: Another very inexpensive supplement that we sorely need is vitamin D3 (cholecalciferol), a fat-soluble vitamin. In addition to the widely recognized importance of vitamin D3 for calcium metabolism,17 it also plays an important but less well known role in serotonin metabolism18 and immune function.19 When vitamin D3 is present in the body in sufficient quantity, it actually is not a vitamin but functions as a steroid hormone, 20 contributing to adrenal and sex hormone synthesis and normal function. We are discovering a relative epidemic of vitamin D3 deficiency across the nation and world. 21 While fat-soluble vitamins are a class of vitamins that we typically monitor closely for possible toxicity, vitamin D3 toxicity is rarer than hen’s teeth.22 From an evolutionary standpoint, we were designed to be outside and unclothed 24 hours a day. Given that we’re unlikely to go back to getting that much sunshine
to raise our vitamin D3 levels, we may be well served to have our D3 levels measured and begin supplementation. Almost universally, physicians agree that vitamin D3 levels of at least 60 nmol/l and perhaps as high as 80 to 100 nmol/l are needed for our bodies to function in the way they are supposed to. The vast majority of adults will do very well with supplementation of 5,000 Iu daily; it should be in the D3 form, and levels should be followed. Omega-3 fatty acids: Omega-3 fatty acids are another class of widely deficient nutrients in the united States.23 With tremendous anti-inflammatory effects, omega-3 fatty acids are commonly called “God’s ibuprofen.” Most of us think of fish oil as our major source of omega-3s, but another fabulous source are leafy green foods.24 However, we’re unlikely to fill our dry omega-3 wells with diet alone, so supplementation is important. Source is very important with fish oils. It’s important to choose brands that test and control their quality rigorously, and it is best to ensure that the company removes the organs before pressing the flesh to minimize the toxicities now present in so many fish. Probiotics: Another significant deficiency in most of us that is easy to supplement is probiotics. It is widely understood that probiotics help us to digest our food and make better stools. Entire textbooks have been written about the myriad roles probiotics play in the health of humans; most especially they are immensely important to immune function.25 It’s gratifying that most clinicians now recommend probiotic replacement in the event that antibiotics are needed. Multivitamin: Last on our list of cost-effective supplements is a good comprehensive multivitamin. It should be rich in B-vitamins and replete with absorbable minerals. There are many good brands out there, and many are very inexpensive. RELAXATION Studies have focused for years on the negative impact that negative emotions have on our health. Recently, greater attention has focused on
1. Peng F, Labelle LA, Rainey BJ, Tsongalis GJ. Single nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene are common in US Caucasian and Hispanic American populations. Int J Mol Med. 2001 Nov;8(5):509-11. Schulteis D. New evidence favors the folate hypothesis for autism. Pediatric Academic Societies (PAS) and Asian Society for Pediatric Research 2011 Annual Meeting, Denver, CO. Abstract 3843.506. Presented May 3, 2011. Boris M, Goldblatt A, Galanko J, James SJ. Association of MTHFR gene variants with autism. Journal of American Physicians and Surgeons. 2004 Winter;9(4):106-8. Miller GE, Cohen S, Ritchey AK. Chronic psychological stress and the regulation of pro-inflammatory cytokines: a glucocorticoid-resistance model. Health Psychol. 2002 Nov;21(6):531-41. Kiecolt-Glaser JK, Glaser R, Shuttleworth EC, Dyer CS, Ogrocki P, Speicher CE. Chronic stress and immunity in family caregivers of Alzheimer’s disease victims. Psychosom Med. 1987 Sep-Oct;49(5):523-35. Wang L, Muxin G, Nishida H, Shirakawa C, Sato S, Konishi T. Psychological stress-induced oxidative stress as a model of sub-healthy condition and the effect of TCM. Evid Based Complement Alternat Med. 2007 Jun;4(2):195-202. Forlenza MJ, Miller GE. Increased serum levels of 8-hydroxy-2’-deoxyguanosine in clinical depression. Psychosom Med. 2006 Jan-Feb;68(1):1-7. Ochi M, Tominaga K, Tanaka F, Tanigawa T, Shiba M, Watanabe T, Fujiwara Y, Oshitani N, Higuchi K, Arakawa T. Effect of chronic stress on gastric emptying and plasma ghrelin levels in rats. Life Sci. 2008 Apr:82(15-16):862-8. Epub 2008 Feb 16. 9.
the countervailing power of positive emotions to influence our health and well-being.26 In this regard, one of the least expensive and perhaps most useful ways we can be effective in caring for ourselves is to use techniques of relaxation, imagery, and affirmation. These can help us change how we perceive our world, ourselves, and our day-to-day experiences. Relaxation techniques are numerous, and many are very effective. Most guided imageries last from 5-15 minutes and may, therefore, be reasonable things for us to find time to do during the day. The recent advent of relaxation techniques that employ mindfulness and gratitude have proven to be one exceptionally effective way to influence our mental and physical well-being. 27 An example of such a program is HeartMath, which offers relaxation techniques for both adults and children. HeartMath programs for children have been used very successfully by some of our children with ASD. What is fascinating is that parents of children with ASD who practice HeartMath techniques have been found to influence not only their own health but also the health of their children. HeartMath practice only requires five minutes daily, and the effects are sustained for many hours after the practice. conclusIon Often, we feel as though we are swimming upstream as we seek to heal our children. The process can be expensive and challenging, and frequently we find ourselves feeling isolated and frustrated. What I have tried to show here is that it is critically important for us to care for ourselves. As parents of children with autism, we experience extraordinary stress as we work to survive and hopefully thrive with autism. Acknowledging that the stress of caring for a loved one with sometimes extraordinary special needs is extremely challenging allows us to recognize that it is imperative to find effective ways to care for ourselves. Fortunately, there are many things we can do for ourselves that are costeffective and require relatively little time. I still hold out hope for the wedding and the grandchildren--for my daughter and for my patients. But in my post-cancer life, there is a new corollary to this hope. I want to be here and healthy so that I can participate in those events.
Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A. 2004 Dec;101(49):17312-5.
19. Partonen T. Vitamin D and serotonin in winter. Med Hypotheses. 1998 Sep;51(3):267-8. 20. Reichel H, Koeffler HP, Norman AW. The role of the vitamin D endocrine system in health and disease. N Engl J Med. 1989 Apr;320(15):980-91. 21. Mithal A, Wahl DA, Bonjour JP, Burckhardt P, DawsonHughes B, Eisman JA, El-Hajj Fuleihan G, Josse RG, Lips P, Morales-Torres J; IOF Committee of Scientific Advisors (CSA) Nutrition Working Group. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009 Nov;20(11):1807-20. Epub 2009 Jun 19. 22. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr. 1999 May;69(5):842-56. 23. Connor WE. Importance of n-3 fatty acids in health and disease. Am J Clin Nutr. 2000 Jan;71(1):171S-175S. 24. Meyer BJ, Mann NJ, Lewis JL, Milligan GC, Sinclair AJ, Howe PR. Dietary intakes and food sources of omega-6 and omega-3 polyunsaturated fatty acids. Lipids. 2003 Apr;38(4):391-8. 25. Rastall RA, Gibson GR, Gill HS, Guarner F, Klaenhammer TR, Pot B, Reid G, Rowland IR, Sanders ME. Modulation of the microbial ecology of the human colon by probiotics, prebiotics and synbiotics to enhance human health: an overview of enabling science and potential applications. FEMS Microbiol Ecol. 2005 Apr;52(2):145-52. 26. Fredrickson BL. Positive emotions. In: Snyder CR, Lopez SJ (Eds.), Handbook of Positive Psychology (pp. 12034). New York: Oxford University Press, 2002. 27. McCraty R, Barrios-Choplin B, Rozman D, Atkinson M, Watkins AD. The impact of a new emotional selfmanagement program on stress, emotions, heart rate variability, DHEA and cortisol. Integr Physiol Behav Sci. 1998 Apr-Jun;33(2):151-70.
10. Singh NA, Clements KM, Fiatarone MA. Sleep, sleep deprivation, and daytime activities: a randomized controlled trial of the effect of exercise on sleep. Sleep. 1997;20(2):95-101. 11. Puetz TW, O’Connor PJ, Dishman RK. Effects of chronic exercise on feelings of energy and fatigue: a quantitative synthesis. Psychol Bull. 2006 Nov;132(6):866-76. 12. Broom DR, Batterham RL, King JA, Stensel DJ. Influence of resistance and aerobic exercise on hunger, circulating levels of acylated ghrelin, and peptide YY in healthy males. Am J Physiol Regul Integr Comp Physiol. 2009 Jan;296(1):R29-R35. Epub 2008 Nov 5. 13. Ross R, Dagnone D, Jones PJ, Smith H, Paddags A, Hudson R, Janssen I. Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men: a randomized, controlled trial. Ann Intern Med. 2000 Jul;133(2):92-103. 14. Pedersen BK, Hoffman-Goetz L. Exercise and the immune system: regulation, integration, and adaptation. Physiol Rev. 2000 Jul;80(3):1055-81. 15. Byrne A, Byrne DG. The effect of exercise on depression, anxiety and other mood states: a review. J Psychosom Res. 1993 Sep;37(6):565-74. 16. Dimova S, Hoet P, Dinsdale D, Nemery B. Acetaminophen decreases intracellular glutathione levels and modulates cytokine production in human alveolar macrophages and type II pneumocytes in vitro. Int J Biochem Cell Biol. 2005 Aug;37(8):1727-37. Epub 2005 Apr 26. 17. DeLuca HF, Paaren HE, Schnoes HK. Vitamin D and calcium metabolism. Top Curr Chem. 1979;83:1-65. 18. DeLuca HF, Cantorna MT. Vitamin D: its role and uses in immunology. FASEB J. 2001 Dec;15(14):2579-85.