By the time March hit this year, I was burnt out. Which, considering what the previous 6 months were like, was pretty much guaranteed to happen. Let me explain.

August 2014 – my grandmother passed away. Without getting into the details, this was one of the most emotionally turbulent few weeks of my life.

September 2014 – we bought our first house! And the house we bought was perfect for also opening a home-based medical office. We finally had answers for so many questions regarding our future. However, it also was incredibly stressful. Buying a house when you’re both self-employed is extremely challenging. So even after we had a commitment from our mortgage lender, it felt like the rug could be pulled out from under us at any moment. Neither of us felt comfortable with the situation until we closed on November 10th.

October 2014 – continue my normal amount of work (job, clients, blog, book-keeping for my husband’s business, the majority of the household responsibilities) and add in launching a new business. I was suddenly the go-to between our lawyers and insurance team, a receptionist for my husband’s new clinic and the coordinator of marketing, business development, website creation and operations. Oh and add in packing up our home (the second time in less than a year – brutal!).

November 2014 – we took possession of our house on November 10 and immediately started some basic reno’s to make it appropriate for a home-based business. We managed to pull everything off in less than 3 weeks. We moved in on Sunday November 23 and continued working at our current clinic through til Friday November 28. At which point we had 4 days off to move our offices and set up our brand new ones because we launched our new clinic on Wednesday December 3. It was insane.

December 2014 – new clinic launch!! It was 100% successful, which was amazing. There were hiccups and bumps in the road, but we were able to navigate those fairly easily. The one good thing is we weren’t launching a business from scratch – we’ve both been practicing for a while so we knew exactly what we needed to do. Even still, December was a bit of a blur. I was in constant hyperdrive managing our new clinic, putting out small fires and figuring out all of the little details as they came up.

January to March 2015 – continued similarly to December, at a slightly less frantic pace. But add in a brutal winter.

 

Major Health Issues I Was Experiencing

1. Two days before Christmas I came down with an epic case of the flu. Nausea, headaches, fatigue, extreme bone and joint pain – the whole nine. I didn’t feel 100% back to normal for 2.5 weeks. It just goes to show, you can’t out-eat and out-supplement stress.

2. I skipped a period. This is something I have never experienced before so it kind of shook me. At first it was an additional stress because I thought I might be pregnant, and it was literally the worst timing (I had a newborn business baby to raise!!) However, more importantly I took this as a major red flag. The female body is incredibly smart and it protects itself very well. It will suppress its own fertility when it is not an ideal environment for being pregnant and/or having a baby. Too few calories, too low fat, nutrient deficiencies and chronic stress (in the classic emotional sense, or from the perspective of poor food choices, consumption of foods you’re allergic too etc.) are all major indicators to the body that there is famine and/or danger. It knows that it is dangerous to the body to be pregnant during this time, so it literally prevents it. Stress, my friends, is the greatest prophylactic! (side note: any issues in your fertility is a strong indicator that something else is out of whack in your body – irregular cycle lengths, skipping periods, wicked PMS, changes in your normal cycles, endometriosis, PCOS – all are signs that something else is going on and you should address it with a trained health professional)

3. Total and complete inability to handle any stressful situation, no matter how small the issue. The number of meltdowns I had during this 6 month period is kind of embarrassing. Thank goodness my husband knew what he was getting himself into when he married me and also knows how to keep me calm ie. bear hugs and foot rubs – he’s a saint!

4. Resurgence of anxiety. This has been a lifelong health issue of mine that I have mostly been able to recover from, but none of my old tricks were working anymore. I would wake up every morning with an incredible amount of pressure on my chest. Every time our clinic phone rang my adrenaline skyrocketed. It made no sense.

5. Digestive flares. My digestion is the weakest point in my body. Healing it has been the driving force behind all of my nutritional choices. And I can confidently say that I had it 99% figured out! But things started getting out of whack again. I was having the hardest time digesting my food and was constantly having to take digestive support supplements and apple cider vinegar, with no success at weaning myself off either.

6. Extreme and total fatigue. I would sleep 11 hours and wake up fatigued. After 2 large cups of very strong coffee in the morning, I would finally be energized, only to crash mid afternoon. Caffeinated tea and dried fruit got me through, if not an impromptu nap on the couch. I would crawl into bed feeling like I hadn’t slept in days and crash hard, only to wake with a panicked start at 4:00am thinking I had missed my alarm.

 

What The Hell Was Going On??

 

Instead of guessing, we decided to do some testing so we knew exactly what was going on with me. The tests we ran were:

– general CBC, specifically for iron levels

– thyroid panel and complete autoimmune panel (after recently learning that my maternal grandmother had lupus)

– thyroid ultrasound

– salivary cortisol testing, for adrenal function

– genetic testing through 23andMe, looking for the possible MTHFR mutation

My bloodwork actually came back good (much to my dismay). My iron levels were moderate for the first time in my life, which I attribute to regular liver consumption. And my thyroid and other autoimmune indicators came back negative. I was happy to see that, but also a little bummed, because I still didn’t have any answers.

Then came my salivary cortisol test results, and the answers started coming. I had Stage 2 Adrenal Fatigue.

 

What Is Adrenal Fatigue?

I’m going to try and quickly summarize what Adrenal Fatigue is, but I don’t want to write a novel (although, this quickly became a very lengthy post), so at the bottom of this post are a bunch of links to additional resources if you want to read more about Adrenal Fatigue. There are so many incredible resources out there so be sure to check them out!

Your adrenal glands are situated on the top of your kidneys. They are responsible for your stress response. When you are faced with a stressor, they only have one way of responding – as if you are being chased by a grizzly bear. It kicks your entire body into high gear, flooding the system with stress hormones (cortisol is a main one, but there are others as well) that are designed to save your life. This is called the “fight or flight response”. These hormones turn off any systems in the body that are unnecessary for saving your life. That means your digestive, immune, rebuilding and healing systems are turned off (hence my wicked flu and chronic digestive issues).

Now, we are definitely not being chased by a grizzly bear on a daily basis, but the body has not yet adapted to our new lifestyle. The fight or flight response will be turned on by any perceived stress such as:

• financial stress
• work stress
• deadlines
• chronic exercise / overtraining
• exposure to toxins and / or foods that you are intolerant too
• chronic consumption of nutrient-poor foods, specifically insulinogenic foods like sugar, refined carbs, low-fat dairy and grains (aka. The Standard American Diet)
• lack of sleep
• waking up to an alarm clock
• light exposure after the sun goes down

As you can see, it’s non-stop. The very nature of life these days, is working against us. Our bodies are designed for short bouts of stress and then have them be done with. Instead our adrenal glands are firing all day every day, so as you can imagine, they start to get tired.

 

Hypothalamic Pituitary Adrenal Axis Dysfunction

The term “Adrenal Fatigue” is a casual one, that is not recognized by the medical community. So if you go to your doctor and say ‘I think I have adrenal fatigue’ they’re going to tell you to stop googling. However, HPA Axis Dysfunction is absolutely a recognized medical condition and that’s what most of us are talking about when we use the term “Adrenal Fatigue”. 

The impact of chronic stress on the adrenal glands is very powerful. With chronic stress, comes chronic stimulation of our fight-or-flight response, which means cortisol is being secreted on a regular basis. The body becomes less responsive, so even more cortisol gets secreted leading to chronically elevated cortisol levels throughout the day and night. This is Stage 1 Adrenal Fatigue – also known as the Alarm Stage. If the stressors continue, the adrenal glands start to slow down, or get fatigued and they actually produce less than ideal amounts of cortisol. This is Stage 2 Adrenal Fatigue – or Resistance Phase. Stage 3 is when they stop producing cortisol altogether – Exhaustion Phase.

It actually gets a little more complex than this as you leave Stage 2 and get into Stages 3 (and 4 in some models). As your body fights to make more cortisol, it actually steals the building blocks from your sex hormones (estrogen, progesterone, testosterone) to make cortisol. So you end up with a myriad of health issues surrounding sex hormones. Read more about that here. At this point you’re literally fighting to get through the day, regardless of how “well-rested” you are. 

 

Symptoms of Adrenal Fatigue

The symptoms associated with Adrenal Fatigue are broad and can vary from person to person. Chronic fatigue is usually present, but any combination of these symptoms is possible: 

• Low blood sugar, or;
• Elevated blood sugar. Since your muscles require blood sugar to function optimally and if you’re running away from a lion, you’re going to need that fuel! If you’re not then burning that blood sugar, it can result in blood sugar levels in the range of pre-diabetes or even diabetes. Simply from stress!
• Suppression of the immune system. Catching every cold or virus out there.
• Suppression of the digestive system. Stress causes leaky gut. Which in and of itself is one of the underlying causes of most health conditions these days. It also means you are at further risk of getting sick. It also suppresses stomach acid production, which is critical for every step of digestion from nutrient absorption to enzyme release. Insufficient stomach acid leads to nutrient deficiencies, constipation, gall bladder issues, leaky gut and increased susceptibility to pathogenic microbes.
• Chronic low energy
• Major energy crash mid-afternoon
• Difficulty getting out of bed in the morning
• Low thyroid function
• Difficulty losing weight
• Wait gain, specifically around the mid section, or as “love handles”
• Low blood pressure
• Dizziness upon standing
• Low or no libido
• Salt and/or sugar cravings
• Anxiety and/or depression  
• Second wind late in the evening when you’re trying to sleep or feeling “tired and wired”
• Waking up in the middle of the night with the mind racing
• Hormonal imbalances (eg. worsening PMS, changes in menstrual cycle, low testosterone)

 

Test, Don’t Guess

If you suspect you might be suffering from Adrenal Fatigue, find a practitioner who will run a salivary cortisol test for you. It’s a simple test where you spit into 4 tubes throughout the day – upon waking, pre-lunch, pre-dinner and before bed. It gives you a fairly accurate picture of what your cortisol levels are at during the day. 

Ideally your cortisol levels should be the highest upon waking – but not too high so you wake buzzing or anxious! Cortisol should gradually decline throughout the day – with the lowest levels being at night time. As always, there’s a range of normal values depending on each individual. There are a variety of dysfunction patterns, but in general in Stage 1 your cortisol levels are above normal throughout the day, often following the same general decline, but still higher than ideal and sometimes spiking at the end of the day (that tired but wired feeling). Stage 2 you cortisol levels are below normal, or might be normal first thing in the morning and then plummet and stay low throughout the day. In the Exhaustion Phase or Stage 3 cortisol is bottomed out upon waking and stays low all day. Here is a good visual aid for different cortisol dysfunction patterns. 

Treatment of adrenal fatigue will vary depending on what stage you’re in. Some supplements encourage production of cortisol, which you definitely don’t want if you’re in Stage 1, but would be absolutely appropriate for Stage 2. That being said, there are a variety of diet and lifestyle changes you can implement to start the recovery process, halt the progression or simply prevent from occurring in the first place.

 

Dietary Recommendations for Adrenal Fatigue

• eliminate foods that are known to cause inflammation and stress in the body
  • at minimum this should mean avoiding sugar, gluten and vegetable oils
  • ideally also avoiding grains, legumes and poor quality dairy (some people tolerate raw, grass-fed dairy just fine!)
  • depending on your health status, it may also mean adopting an autoimmune protocol or doing additional food allergy testing
• focus on nutrient-dense, healing foods such as organ meats (specifically liver), pastured egg-yolks (if tolerated), grass-fed beef, wild fish and seafood, bone broth and fermented foods (such as sauerkraut and kombucha)
• always eat breakfast, specifically a high protein breakfast (we’re talking 25-30g of protein, so more than 2 eggs!!)
• don’t skip meals – aim for 3 balanced, nutrient dense meals a day, and maybe 1 snack if you need it. Do not attempt intermittent fasting! Intermittent fasting is generally not ideal for women, and definitely not indicated for people with Adrenal Fatigue since it is a major stressor on the body. If you’re having serious blood sugar spikes and crashes, you may need to start your recovery process by eating every 2-3 hours. The goal would be to move towards a 3-square meals approach, once you begin to recover. I recommend working with a skilled practitioner on implementing such a dietary intervention.
• salt your food liberally (himalayan pink salt, celtic sea salt), because adrenal fatigue also results in suppressed aldosterone levels – the hormone for maintaining proper salt levels in your body
• consume carbs – when switching to a real-food / paleo-type diet, it is common to accidentally go “low-carb” which in itself can be very stressful on the body, specifically the female body. Additionally, thyroid function is usually suppressed, secondary to adrenal fatigue, and since carbs are required for conversion into the active thyroid hormone, a low-carb diet will suppress thyroid function even more. Focus on healthy carbs like root veggies and starchy tubers. Include sweet potato, plantains, carrots, beets and moderate amounts of fruit.
• kick the caffeine – caffeine triggers a cortisol spike, and right now you need to normalize cortisol secretion
• limit alcohol – booze not only causes leaky gut, but it also depletes the body of nutrients and stresses the liver – none of this is ideal for recovering from adrenal fatigue
• support digestion with apple cider vinegar or HCl tablets if indicated (under the guidance of a qualified practitioner) and/or support with digestive enzymes

 

Lifestyle Recommendations for Adrenal Fatigue

• manage your stress!! This is the most important part of the entire adrenal fatigue recovery process. Stress is what got you into this pickle in the first place, so even if you do every other thing right, if you don’t address this, you will not recover. That means it’s time to take a critical look at what is causing you stress and actually deal with it. It may be as simple as asking for help and learning to say no, or as challenging as quitting your job or getting out of a toxic relationship. It is likely going to be a combination of things, so start slowly and begin to make real, long-standing changes to your life to reduce stress for good
• sleep for a minimum of 8 hours per night, ideally 9 or 10
• go to sleep when it’s dark, rise with the sun – ideally wake without the use of an alarm clock
• focus on quality of sleep by getting rid of all artificial light in the bedroom, investing in black-out blinds and wearing a sleep mask (although this doesn’t cut it by itself, because your skin still has receptors for light)
• avoid screens for 2 hours before bed and dim the lights in the house – if you can’t avoid screens at night, download the f.lux app for your computer and invest in a pair of geeky blue-light blocking glasses. Why? the blue light from our phones, laptops and TV emit the same type of light as the sun, so our bodies think it’s day time. Melatonin – the sleep hormone – gets suppressed and we are unable to achieve quality sleep
• expose your eyes to sunlight as soon as you can when you wake up – this suppresses melatonin production and tells your body it’s daytime, setting you up for the natural diurnal melatonin rhythm 
• stop intense exercise and/or reduce frequency of exercise  – since exercise is an inherent stressor, hitting the gym every day for an intense HIIT workout, or training for a marathon is only going to make your situation worse. If you do continue to exercise, listen to your body and don’t exercise when you’ve slept less than 8 hours, if you’re feeling particularly fatigued or if you are still sore/achey/tired from your last workout
• build in planned rest or low-key times during the day – aim for a total of 30-60 minutes, either all at once or in chunks over the course of the day. Meditation, gentle stretching sessions, going for a walk, reading a magazine, listening to an audiobook – whatever allows you to relax intentionally is a great option
• connect with nature
• include play-time on a weekly basis – this might mean playing a sport, performing in a music ensemble or playing with your kids – whatever it is, it should be fun!
• connect with loved ones – human connection is one of the most important health predictors and it should not be overlooked during your recovery process. It is tempting to become a hermit when you’re recovering from adrenal fatigue, but make sure to include quality time with friends and family. Go for (herbal) tea with a friend, take a walk with your family or have an old-fashioned movie night at home
• laugh

 

My Personal Treatment Plan for Recovering from Adrenal Fatigue

In addition to getting the results of my salivary cortisol test, I also received my genetic testing results from 23andMe. Now, there’s a lot we don’t know about genetic testing and honestly, getting the testing done can often cause more damage than good. We have seen many clients get genetic testing done and then obsess or panic about their results. The reality is we are so far away from understanding exactly how to use such genetic information, that we really can’t make conclusive decisions from the data we can gather. We have no idea how the body has learned to adapt and how much of an influence our environment has on each individual gene / SNP. Chris Kresser once said:

Your genes load the gun, but the environment pulls the trigger.

So you must take genetic testing with a grain of (sea) salt. I strongly recommend working with a practitioner if you decide to go down that road. That being said, there are a few genetic mutations that we have an okay understanding of. One of them is the MTHFR gene – which was my major reason for doing this test, due to our work with autism spectrum and autoimmune conditions. My results came back with the normal variant of MTHFR, but it turns out I have a few other key mutations. One is a significantly decreased ability to methylate (ie. activate) vitamin B12, so a simple way of managing this is to consume B12 in food (ie. chicken liver) and to supplement with sublingual methylated B12. The most interesting piece of info is I have a double mutation for the MAO SNP. MAO (or monoamine oxidase) is responsible for degrading catecholemines, and my DNA codes for a very slow version of MAO. In plain english – my body/brain has a hard time breaking down stress neurotransmitters. That means when I experience stress, my body stays in a stressed state way longer than someone with the normal MAO SNP. Now, my body may have adapted by sending in other enzymes to help out – we really don’t know that much, but I was able to take away this important point:

My body responds to stress way more dramatically than the average person, which means I am more susceptible to the negative effects of stress and therefore am much more likely to suffer from HPA axis dysregulation.

Well, I didn’t need an expensive DNA test to tell me that! Ha! Or maybe I did…because those results were the final kick in the pants I needed to stop putting stress management lower on my list of priorities. Managing my cortisol is now and forever going to be a top priority for me. 

In the meantime, here’s what I did to help my body recover from adrenal fatigue:

1. I sleep a minimum of 8 hours every night now, and if I don’t, I’m not allowed to exercise the next day
2. Speaking of exercise, I limit my workouts to 3, very rarely 4 days per week, and if I’m sore or tired, I don’t go. When I am at the gym, I listen to my body and don’t overdo it.
3. I stopped eating eggs for breakfast and started eating meat (don’t freak out, eggs are healthy, but I wasn’t able to get in the super high protein that I needed). Eating leftovers for breakfast actually helped me achieve a few things:
   1. high protein breakfast
   2. eating more seafood and broth at lunch, since I have leftovers for breakfast, I often have sardines, tuna and/or soup with homemade broth for lunch
   3. recover better from the gym
4. I really dialled in my nutrition. Now, I’m always pretty on point with my food choices, since that’s how I keep all my nasty health issues from resurfacing, but now it was time to really emphasize the things my body needs, such as:
   1. bone broth at minimum 5 days/week and additional grass-fed gelatin regularly 
   2. seafood 2-4 days/week, ideally sardines when possible (I achieved this by making tuna and/or sardine salad for lunch when I didn’t have leftovers) to obtain lots of omega-3 fatty acids and other nutrients. I also began taking fermented cod liver oil to further support my omega-3/omega-6 balance 
   3. liver/organ meat at least once a week (I achieved this by making chicken liver pate every other weekend and having it for lunch a few days that week, as well as having burgers once a week – note: my burgers contain ground beef, bacon and beef heart)
   4. emphasis on sea salt, particularly kelp-infused sea salt (to get sufficient thyroid-supporting minerals, cause my thyroid is likely suffering a bit, secondary to my adrenal fatigue)
   5. continued emphasis on probiotic food consumption
5. I supported my digestion with apple cider vinegar 10 minutes before meals, add in digestive enzymes if things are not feeling optimal
6. I significantly reduced coffee. I tried cutting it out cold turkey, but had reactive anxiety which was a total bummer. I normally just drink one large cup in the morning (except for Jan-Mar when I was doing 2 cups). So I went back to 1 large cup, then a true 8oz cup and I’m now on a half-caf espresso where I combine regular and decaf to further reduce my caffeine. While I never drank tons of coffee, I have been consuming it pretty much since I was in high school, because I LOVE it, so weaning off is definitely a slow process for me. (UPDATE: As of June 2015 I only drink decaf)
7. I became really strict about exposing my eyes to blue-lights after 8pm. I even purchased some blue-blocking glasses for the occasional evening when we watch TV after dinner. My husband hasn’t stopped laughing at me!
8. I did a bit of a social media detox. I fell into an addictive habit of always keeping on top of Instagram, and often Facebook. Every morning I would get up, make a cup of coffee and scroll through the previous 24 hours on Instagram before I hit the gym. I thought it was a nice, calm, enjoyable way to start the morning. Then my husband told me about something he read where the constant influx of information every half second as you’re scrolling through social media, can be incredibly stressful for the brain. So I switched to reading in the morning and it has made a huge difference! I take this opportunity to read informative books (health, nutrition etc.) because I if I read those before bed I get too excited to implement my new knowledge!
9. I identified my stressors and dealt with them. I am incredibly grateful for the opportunity we have to make a career out of something we are so passionate about and I wouldn’t trade it for the world. It feels a little weird complaining about something I feel so lucky to have achieved, but I have to be honest. Even something I love can be hurting me. So I got realistic about the parts of the job that were really stressing me out and I did something about it! We hired a part time receptionist to take the admin load off my shoulders. And we also brought on a volunteer student 1 day a week this summer to help me work on some projects I’ve kept having to put off. 
10. Laugh. I put my foot down and officially said no more sad or stressful movies/shows etc! From here on out I am only watching things that make me laugh.
11. I saw my chiropractor twice a week for the first few weeks and then down to once a week maintenance. Maintaining proper nervous system function is key when recovering from any health concern – not to mention maintaining a healthy body in general. Chiro’s are not just for musculoskeletal injuries!
12. I started a specific supplement protocol, geared to my health status. I am not going to share this in detail, because everyone’s situation is slightly different and if you implement my supplement protocol, you might make your situation worse. However, there are a few safe supplements that can help:
    1. Vitamin C is critical for proper adrenal health, and while you can get it from vegetables, extra in the form of a supplement can really help right now
    2. Vitamin B Complex is also critical for adrenal health. Ideally you want one with a methylated folate (methyltetrahydrofolate), especially if you have an MTHFR mutation
    3. Magnesium – most people are low in magnesium, as it is low in our food supply and it can get depleted so easily by stress, medications (birth control is a big one), exercise, menstruation. It is also effective for maintaining healthy bowels!
    4. Holy Basil Tea – Holy Basil, or Tulsi, is an stress adaptogen which means it normalizes your stress response. So whether your stress response is over- or under-stimulated, it brings it to normal.
13. We got a puppy!!! Now I know most people would thing, “wait, aren’t you trying to reduce stress and decrease the amount on your plate?” Yes, absolutely. But adopting a dog was actually part of my recovery plan. My husband and I have wanted a dog for years, but our lives never allowed for it. Now that we have a home-based business, we can actually manage it! Let me paint you a quick picture: The house that I live in, is also the one I work at and my life partner also happens to be my business partner. So you can imagine how impossible it can be to get away from work – and no matter how much we love what we do, separation is key. Getting our girl Ruby was absolutely crucial for adding in that separation. Our dinner talk no longer consists of business chitchat, and now revolves entirely around how silly she is. It’s really bad, we’re like new parents! Also, she is a high energy puppy who requires at minimum 2x 45 minute walks a day, which means I am forced at least once a day (sometimes twice if my husband’s schedule can’t accommodate her second walk) I must get outside and disconnect from all things work, life and stress! Walking Ruby helps me to:
    1. get outside every day and connect with nature
    2. laugh – because she’s ridiculous
    3. actively rest by listening to a favourite podcast
    4. move my body in a stress-free, primal way

Within a few weeks I started noticing improvements – it was actually quite dramatic how quickly I started to feel better. However, even with the improvements I know that this will be an on-going journey. As a recovering Type-A personality who is predisposed to adrenal fatigue, I will continue supporting my health from all angles, with a priority on my adrenal health, as a project likely for the rest of my life. And you know what? I’m totally okay with that. Because it means that I will be taking care of my body, laughing more, connecting with loved ones and nature more, learning how to say no and not sweating the small stuff. If you ask me, that’s a damn good way to live!

 

So tell me – does any of this ring true with you? Have you experienced adrenal fatigue? What are you doing to help your body recover from it?

 

Additional Resources

Podcasts:

Balanced Bites Episode #189: Overcoming Adrenal Fatigue with Laura Schoenfeld, RD

The Paleo View Episode #136: Adrenal Fatigue

Balanced Bites Episode #15 (with Dan Kalish), Episode #39 (listener Q&A), Episode #46 (with Dan Kalish again) and Episode #189 all on Adrenal Fatigue.

Blog Posts:

Chris Kresser – The Modern Lifestyle: A Recipe for Adrenal Fatigue?

The Paleo Mom – How Chronic Stress Leads to Hormone Imbalance (all my ladies out there – READ THIS!!)

Diane Sanfilippo on RobbWolf.Com – The Real Deal on Adrenal Fatigue

Websites:

Adrenal Fatigue Solution

Books:

Your Personal Paleo Code by Chris Kresser Bonus Chapter #28: Adrenal Fatigue Syndrome, which has been rebranded as The Paleo Cure

The Adrenal Fatigue Solution by Fawne Hansen with Dr. Eric Wood

Programs for Recovery:

Paleo Rehab: Heal Your Adrenal Fatigue