Click on the link above to access a presentation recently prepared to explain a gluten free diet and resources for the PWN interested in adopting the diet!
Histamine is critical for maintaining arousal and wakefulness. The sole source of histamine in the brain is a region called the TMN (tuberomammillary nucleus) in the posterior hypothalamus. The hypothalamus is also where orexin comes from in the brain. Like orexin, neurons which make histamine (called histaminergic neurons) have far-reaching projections in the brain. Because of this, again, like orexin, these neurons are implicated in many different physiological states including sleep-wake control, learning, emotional status, and memory formation.
Most of us have experienced the histamine wakefulness-promoting effect when we have taken anti-histamines (Benadryl, etc.). The #1 side effect that most people notice is drowsiness. This is due to the fact that anti-histamines bind and antagonize histamine receptors (H1 receptors). Anti-histamines block histamine signaling in the brain.
In health, histominergic neuron activity is highest during wakefulness, and is becomes nearly undetectable during sleep (REM and NREM).
It has been shown previously that people with narcolepsy have low CSF histamine. In addition, the lower the corresponding orexin levels, the lower the histamine levels; indicating that proper orexin signaling in the brain is crucial for proper histaminergic signaling. The same trend has been shown for those with idiopathic hypersomnia.
Mouse models have also demonstarted a link between histamine and sleep impairment. Histamine deficient (HDC KO) mice display sleep fragmentation and increased REM sleep during the light period along with profound wakefulness deficit at dark onset, a condition that sounds intriguingingly similar to narcolepsy. Moreover, sex differences in histamine deficiency have been demonstated in mice: female HDC KO mice demonstrated “hypoactivity, increased measures of anxiety, impairments in water-maze performance, but enhanced passive avoidance memory retention.”
Histamine has also been implicated in neurogenesis. I’ve already discussed this concept to some degree here (although I should point out that was discussing a different region of adult neurogenesis). This has been demonstrated largely in the subventricular zone (SVZ), which is a known area of adult neurogenesis and has implications for repair following injury. The image below shows the respective regions (SVZ) in relation to the hypothalamus (where orexin neurons are).What does it mean for narcolepsy? Why would narcoleptics have low histamine and a compensatory increase in the number of histmaine-containing neurons?
BIG FAT DISCLAIMER: I am not a medical doctor. The following is not advice or medical recommendation. Please see the official disclaimer here.
I have been off of conventional narcolepsy treatments for 3 years, and gluten free for 4 years. Over time, I have found a host of vitamins and non-prescription nutritional supplements that have greatly increased my wakefulness and helped with other aspects of daily functioning. Please note that this is my personal log. What they are, and how I think they are helping are below.
I began taking L-tyrosine about a year ago following a blog post concerning “Narcolepsy, dopmine and tyrosine“. I started the tyrosine regimen (between six and nine grams a day, broken up into two doses [1 at breakfast, 1 at lunch]) following reading a paper in the Lancet that reported total remission of daytime sleep attacks and cataplexy after six months of treatment. The military has also used L-tyrosine in sleep-deprived pilots to improve performance during long flights. Another report which included more rigorous controls noted that only 3 of 10 patients noted a positive effect, and so L-tyrosine could not be considered therapeutically relevant. Personally, I noticed that at the 9 gm dose I experienced a great deal of anxiety – particularly in the evenings. However, lowering the dose to 3-5 gm per day and them in the morning and early afternoon gives me the benefits of wakefulness during work hours without increased evening anxiety. A summary of how I think it’s working is below:
L-carnitine: I take 1000 mg of L-carnitine per day (500 mg in the morning, 500 mg at night). Carnitine is is an important essential nutrient, and has been demonstrated to be therapeutic for individuals with narcolepsy. Click here for my long blog post on L-carnitine and narcolpesy.
In short, individuals with narcolepsy have very low levels of serum acylcarnitine. Reduced acylcarnitine means impaired fatty acid oxidation, disturbed sleep, and impaired orexin cell functioning.
Oral supplementation of L-carnitine restores β-oxidation (fatty acid oxidation) and mitochondrial ATP generation from fatty acids.
Carnitine also has marked effects on proper intestinal development and function and reduces intestinal inflammation. Carnitine is also necessary for proper immune functioning and promotes regulatory cell function (think: anti-autoimmune). Carnitine supplementation can also improve obesity, glucose tolerance and energy expenditure
From madcapmissadventures, I have learned I have to keep working at this anti-narcolepsy diet thing. If I slack off my diet (or exercise), my narcolepsy comes back with a vengeance. Thank you Gina for just being out there. We CAN beat narcolepsy!
gluten free + low carb = no narcolepsy
Narcoleptic No More – Narcolepsy Pintrest Board
This morning, I found a truly inspiring TedTalk from a woman diagnosed with multiple sclerosis, an autoimmune neurodegenerative disease not completely unlike narcolepsy. Like narcolepsy, which is neurodegenerative and believed to be autoimmune, multiple sclerosis presents as a life-long disability, from which there is “no known cure,” and medications are prescribed only for symptom management.
This life-long disability was not an option for Dr. Wahls, and, like so many of us who receive dissatisfying prognoses and aid from conventional medicine, turned to PubMed to begin searching for her own answer.
What Dr. Wahls found was not only symptom management but reversal of her multiple sclerosis through diet-modification, excluding gluten and grains, and consuming a paleo/hunter-gatherer diet rich in leafy vegetables. Here “cure” came in just 4 short months.
You can find more about Dr. Terry Wahls at her website. Thank you Dr. Wahls for being a outspoken doctor, patient, and advocate of healthy eating for autoimmune disease!
10. I feel incredible. I’m confident that 90% of people would feel 100 times, if not more, better consuming a “paleo”-type diet. I don’t like confining myself to the “gluten-free” or “paleo” movements, but I am both gluten-free and “paleo.” The longer I go without eating processed foods or sugared-alternatives, the more I can feel how food actually affects my body. Whenever I “cheat,” and eat a high glycemic-index meal, I crash and feel like crap for the next day. I don’t like feeling like crap. So I keep eating paleo.
9. Freedom from food. Sugar is addictive. Bread is addictive. Prior to going gluten free, I noticed NOTHING I ate didn’t have some kind of wheat (or at least food starch) in it. In fact, most times, something starchy was the center of the meal. That’s the American way, right? “Here, honey have a roll.” My sugar addiction began when I was young, craving sweets and cakes, anything I could get my hands on. I’m sure I had it worse than some, but maybe not. As I became older, my sugar addiction spiraled out of control, and I had no idea it was even happening. I had learned in school to stay away from candy, but that grains and bread were the bottom of the food pyramid. I was SUPPOSED to be eating >300 carbs per day! When I moved out on my own, I couldn’t keep chips, candy, sugar, ice cream, or even alchol (it’s just another source of sugar for me) in my house for fear I would overeat… and that’s when I started thinking maybe it was the sugar.
Like most “dieting” women I know, I counted calories and fat (like I was instructed to by the bread-on-the-bottom-food-pyramid-nutritionists) like a mad woman. I took my weight 3 times a day. I obsessed over my clothes-size, how I felt in them, and was self-consious to eat in front of people. I would restrict my eating to point of refractory bingeing. Even if I only skipped lunch, I was trying to devour everything in site come dinner. This was before I found gluten free / paleo.
On gluten free / paleo, I no longer obsess over the calories and sugar I am putting into my body. I have complete freedom from the obsession of food. I eat when I am hungry. I don’t eat when I am not. I don’t worry about the nutritional content of what I’m eating most of the time, because my diet is inherently filled with nutrient-dense foods. Simple as that.
8. No more naps. Mid-afternoon crashes are the worst. On paleo, I don’t get them any more. I remember as a highschooler, coming home and sleeping for 2-3 hours every day. I was so fatigued. I have had a nap twice in the past year. Adding it up, that’s more than 730 hours of gained productivity, which is desperately needed as a hard-working graduate student.
7. “I’m regular.” I don’t want to delve into the realm of too much information, but prior to Paleo I was incredibly irregular. Irregular cycles, irregular digestion, irregular sleeping habits, irregular moods. More than that, I had never been regular. Many of my earliest memories of childhood were surrounded by GI problems, mood problems, and sleeping problems… but how was I supposed to know they weren’t normal? No one ever really told me how often I was supposed to be going to the bathroom. Anyway, you name it, on a low-fat, high-fiber diet, mine wasn’t normal. By body’s internal clock was just all warped. On paleo, I’m like a machine. Everything is all “regular,” a feeling I haven’t had in my entire life until now.
p.s. – I hardly ever eat fiber.
6. Better cholesterol. I get made a lot of fun of where I work because I love to eat pork rinds. Lots of them. I will eat a bag for lunch without blinking. They are such a common and frequent part of my diet, that it seldom occurs to me that it’s weird, until someone comments that I am so unhealthy for eating them (ironically, I am the skinniest person at my work). I eat a very high cholesterol diet. I eat red meat once or every other day. I eat about 3 eggs a day. I eat pork rinds to my hearts content (insert pun), and snack on nuts. Sounds like I should have the worlds worst heart, right? Wrong.
I began having my cholesterol monitored after a blood test revealed high LDL and low HDL cholesterol, and high triglycerides. This was a bit scary for me, having a family history of heart disease. My abnormal cholesterol test came at 20, while I was doing a low fat, grain-based diet, and running a mile a day.
Since going “paleo,” my LDL is normal and my triglycerides are down. I still haven’t been able to raise my HDL, despite maintaining very frequent cardio exercise (>5/miles of running per day), but I think this may just be true genetics at play.
5. I’m thinner and more tone. I have never not felt fat. Even when I was thin and severely calorie-restricting, I always felt fat on a grain-based diet. In addition, as I entered late adolescence/early adulthood, I actually started becoming fat, peaking at 150 (quite large for my small 5’3 frame) while in college. I became fat because I was eating the recommended diet of low-fat, whole grain. In addition to becoming fat, I also became sick. On paleo I maintain a healthy and fit 115 no matter how much I exercise or how many bags of pork rinds I eat.
4. I’m happy. All the time. This seems like a weird statement, but, I’m always happy. Literally. I remember struggling with depression as young as Kindergarten. My grandmother told me in my teenage years, when I battled daily with manic depression and fatigue, “sometimes as a child you just looked so sad.” It broke my heart to realize that my family had noticed my sadness at such a young age. On a low-fat, whole-grain diet I cried, screamed, had emotional outbursts, resented, and surfed the lowest-of-lows and highest-of-highs. On paleo, I’m simply happy. That’s it.
3. No more pain. As a young girl, I remember my mother struggling with chronic headaches and backpain. I never knew her agony until I was about 17 years old, when I began having chronic headaches and migranes with auras. I had also had joint pain (primarily knee and back) for most of my life (the doctor’s decided I had “growing pains,” which is code for, “it’s all in your head.”) I dealt with the chronic headache and low-grade aches and pains by taking 800mg of ibuprofen every day. For years. After going gluten free, my chronic pains and headaches subsided, but the auras persisted. When I went fully paleo, the frequency of auras (without pain) reduced from once or twice a day to once every two months or so. They still happen randomly every once in a while, but not nearly with the frequency they used to, and their usually triggered by taking a hot shower. I now take Advil once a month for cramps, but some months I don’t need it at all.
2. Paleo (nearly) cured my narcolepsy. I first became gluten free about a year after I was diagnosed with narcolepsy, and became full paleo about a year after that. Before deciding to become gluten free, I realized I was getting tired after eating, and if I went all day without eating, I was less tired. I went searching and found a truly incredible blog called The Zombie Research Institute. A woman whose brain clearly worked like mine did, who cured her narcolepsy with gluten free? It sounded ridiculous, but I was desperate for anything to work. I tried it. Very strict. And it worked. Gluten free combated narcoleptic attacks and hypnogogic hallucinations, but I feel my most awake and alert by excluding all refined sugars and grains and adhering to a paleo diet.
1. Paleo saved my life. This might seem like an inflammatory statement (another pun), but it’s not a joke. I believe going gluten free (and later paleo) literally saved my life. Throughout my childhood, adolescence, and young-adult years I was only sick and sad. There were many many days where I was quite sure that I wouldn’t make it past 40. I had physically struggled for so long, that I didn’t want to make it past 40. I couldn’t bear the thought of living another 20 years in tiredness and pain. Now, I am exited to age in health and grace; and, actually look forward to tomorrow.
In addition to posting these reasons that I “do paleo,” the new fat-diet of the day, quite proudly, I would also like to take a moment to respond directly to some of the “points” raised in the original post “Top 10 Reasons I’m Not Paleo” by Cheeseslave.
1. To first answer Cheeseslave’s question:
But honestly, if you’ve been eating paleo for any length of time, don’t you miss grilled cheese sandwiches? Quesadillas? Pizza?
Sure. Yes. I miss pizza, pudding, ice cream, M&M’s, and especially peanut butter. I miss sugar the way a 3-pack-a-day smoker misses a cigarette. There is a twinge of pain everytime I see someone eating a doughnut in part because I hate wheat, but also in part because I WANT THAT DAMN DOUGHNUT.
That said, I miss the narcolepsy less than I miss the doughnut.
2. In response to:
Is the modern epidemic of “gluten intolerance” really caused by eating wheat? Or is it possible that something else is causing gluten intolerance?
There is a theory that antibiotic drugs cause an imbalance of gut flora and cause prevent the digestive tract from secreting enzymes that enable us to break down complex proteins such as gluten. Sounds a lot more plausible than the idea that wheat suddenly started causing gluten intolerance out of nowhere.
In the first place, the alternative theory isn’t bad. I agree that something other than gluten could be causing gluten intolerance. Genetics, a changing gut microbiome, antibiotics, sugar, birth control. Alternative theories are fine and dandy, but gluten is a very good candidate, as the protein has been demonstrated to be inflammatory and barrier-compromising to the intestinal tract all on it’s own. It also stimulates antigen presenting cells to be “preactivated” among “normal” healthy individuals without celiac disease or gluten sensitivity. Here’s another one demonstrating positive benefits of gluten-removal from IBS patients who did not have clinical celiac disease. But a different cause for gluten intolerance, doesn’t justify continuing to eat it. It would still be a gluten intolerance; wheat’s fault, or not.
In the second place, gluten isn’t the only thing found in wheat. Wheat germ agglutinin (WGA) is a lectin found in wheat and has been demonstrated to have antinutritive effects irrespective of gluten intolerance and celiac disease. Concentrations of WGA are higher in the seed and young shoots of wheat, to protect it from predation from fungus, insects, and animals. In fungus and insects WGA binds to the chitin. Chitin is found in the cell wall and intestinal system of fungi and insects, respectively. In animals and in humans, it binds strongly to sialic acid on intestinal cells, where it is internalized, and can also agglutinate bacteria and red blood cells. Because it is stable at low pH (i.e. poorly digested) and resistant to gut proteases, it is gaining widespread attention and research to be utilized as a carrier for drug delivery. Once inside epithelial cells of the digestive tract, it accumulates in lysosomes and resists degradation. It alters intestinal permeability, allowing for the passage of small molecules across the intestinal barrier. In addition, in sufficient concentrations, it stimulates proinflammatory cytokine release as well as affecting the activation of immune cells in the gut, and can cause pancreatic hypertrophy. It should be mentioned here that lectins are not only found in wheat (but wheat has among the highest lectin concentrations and is the most prevalent plant lectin), and their entrance into the blood stream and implications on systemic health has yet to be widely investigated. For another good review, go here. How is that for “antimicrobial” theory?
I struggle with anger towards my mom for not figuring out that I was tired after I ate. Because of food, I was sick and sad for most of my life. If only my mother had known or realized that food could affect how you feel SO MUCH, I know she would have changed my diet at a young age and not let me have dessert at all (or, made a nice paleo alternative).
In contrast, I know I will be the most-hated parent on the block when my child realizes that Oreos exist. But, to me, if I were to allow my child to indulge in sugar, I might as well put vodka in their bottle, and a joint in their hand. Sugar is a drug. It works the same on the brain. And I’m sure little Johnny will sneak away to Billy’s house to eat ice cream on the weekends. But I refuse to allow my children to become addicted to sugar and food in the same way that I was. And they sure as heck won’t be sad, sick, or worse for the pie that I put on their plate.
In a previous post, Starving Yourself Awake, I wrote on the eating = asleep phenomenon (i.e. postprandial somnolence) experienced by many people, including those with narcolepsy.
In conducting research for the article, I discovered several key links between orexin activity (orexin expression and orexin receptor expression) and fasting. A few of the important connections are summarized below:
1) Orexins stimulate arousal and wakefulness.
2) Orexins are found in the hypothalamus as well as the gut, and are up regulated during starvation/fasting, and inhibited during feeding (particularly in response to glucose).
3) Women with anorexia have been demonstrated to have higher levels of circulating orexin, while narcoleptics (with cataplexy) have little to no orexin in their CSF.
In addition to the specific effects of fasting on orexin and orexin receptor expression in the brain, fasting has been demonstrated to be effective in management of other autoimmune diseases, including MS, rheumatoid arthritis, and lupus (SLE). To my knowledge, no one has yet scientifically demonstrated this effect in narcoleptic patients.
In light of these findings, I am conducting a 3 day fast to determine it’s effects on wakefulness and energy levels. The last time I ate was 9:00 PM 6/17/2012, and I slept 7 hours last night with no memorable sleep disturbances or hypnogogic hallucinations. I will post daily with reports on energy levels and wakefulness, and hope to provide anecdotal evidence to support (or refute) the use of fasting in narcolepsy.
——–UPDATE – 38 hours———
I have now been fasting for 38 hours. So far so good.
I do not have any remarkable changes in mood or energy level, as of yet. Last night I was less sleepy than I normally am upon laying down, but I didn’t have any trouble falling asleep. Only have had 2 short (less than 5 minute) periods of hunger (complete with tummy grumblings), but otherwise have not felt hungry.
I am hoping to see changes in energy levels and beginning about the 48/60 hour mark. My goal is to do a complete 3 day (72 hour) fast, but would be happy to make it to 48 hours. More updates tomorrow!
—–Update 48 hours——
Because I didn’t see any remarkable changes in energy level or alertness, I broke my fast at 48 hours.
I promptly went to sleep, and have been sleepy since breaking my fast.
That said, becomming sleepy after eating doesn’t really account for the fact that I didn’t feel dramatically more awake on the fast, as I had expected. Now, I did have coffee during the fast – maybe that was what kept me from feeling any better than I did?
Most people who fast for autoimmune therapies do a water only fast, and also may fast for up to two weeks! Especially because I was so dramatically tired after breaking my fast, I would like to reattempt the fast, this time for longer and to do a complete water fast.
I also think that a ketogenic diet (i.e. a diet from only fat and protein) may be more beneficial to narcolepsy than by fasting alone.
In the first place, the benefits of fasting arise from your body’s ability to use fat and protein stores for fuel; carbohydrate metabolism (other than those arising from gluconeogeneis) are not utilized. Secondly, it was recently demonstrated that a diet of amino acids activates orexin producing neurons, and that the excitatory effect of dietary amino acids outweighed the inhibitory effect of glucose.
The best dietary “prescription” to be then would seem to be a gluten-free (benefits covered in other posts), low-carbohydrate ketogenic diet, coupled with bouts of intermittent fasting.
Anyone out there with fasting experience and narcolepsy? Or other low-carbers? What about for the treatment of other autoimmune diseases?
When I first was diagnosed with narcolepsy, I was devastated. I had put together the story that was being told about my brain: probably autoimmune, neurodegenerative, and sorry but you will be this way for the rest of your life. The assumption that there is a neurodegenerative loss of hypocretin/orexin-secreting cells of the hypothalamus in narcoleptic brains is probably not totally inaccurate. Throughout the course of my research, however, I became convinced that an underlying food intolerance could mediate the autoimmune process; if I cut out the food I was intolerant to, I could turn off that process and cool my brain down. And it worked. A month after going gluten free, my symptoms of narcolepsy disappeared.
Even though I was excited to not be tired anymore, I was concerned about this supposed neurodegeneration that was happening in my brain. Even as a scientist, I was taught all throughout school that once you lost a neuron, that was it. Game over. No new neurons for you. However, at the time, there were a few studies coming out demonstrating how aerobic exercise could promote neurogenesis. So — I started running. As I run, I like to image the little dendrites of the hypocretin-secreting neurons I do have left reaching out and making new connections, restoring my narco brain to something not handicapped by some mysterious autoimmune process.
The plan was (and still is) simple: 1) stop all future neurodegeneration by turning off the autoimmune and inflammatory processes (this was made possible by going gluten free), and 2) promote new neuronal growth by exercising every day.
All of that was fine and dandy, but as a rational person, I needed some proof. What if the current view was right? There was always a crippling fear in the back of my mind that I was wrong. That somehow, someway, the narcolepsy was going to win.
I lived with this fear, until I read this paper: Adult Neurogenesis in the Hypothalamus. And there it was. I could stop the inflammation with a gluten free diet, and make new neurons in areas that I thought may have been completely ablated. The realization that we all in fact have the potential to make these new neurons is nothing but relief.
It means, without a doubt, that once you turn off the inflammation, you can turn your brain back on.
In 2004, Dr. A. M. Husain published an article in Neurology called “Diet Therapy for Narcolepsy.” Dr. Husain conducted a study on the effects of a low-carbohydrate ketogenic diet (LCKD) on people with narcolepsy. Basically, he put a few patients on the Atkins Diet, and asked: “Were they less sleepy?” Over the course of just 2 months, the patients that were able to adhere to the diet noted a significant reduction in their total sleepiness (assessed by a Narcolepsy Symptom Status Questionaire). Overall, patients reported an 18% reduction in daytime sleepiness.
So why is this paper interesting?
1. It demonstrates that diet can affect how tired you are.
Food affects how you feel. Particularly, specific foods may make you more tired, especially if there is an underlying intolerance to a specific food group. By eliminating self-identified foods that seem to make you more tired, it is possible to manage the symptoms of narcolepsy, at least in part, through diet modification.
2. It also points to a group of foods that may be causing the sleepiness in the first place!
Low-carbohydrate ketogenic diets (LCKD), such as the Atkins and more recently popular Paleo diets, restrict carbohydrates which usually come from grains. Of these, wheat is the most common source of carbohydrate in the American/Western diet. By going on a low-carb diet, you are in part severely limiting grain and wheat flour consumption.